PMID- 2183809 TI - [Immunohistochemical markers of malignant melanoma]. PMID- 2183810 TI - Hematopoietic growth factors and in vitro growth of human acute myeloblastic leukemia. PMID- 2183811 TI - Systemic amyloidosis. PMID- 2183812 TI - Erythrocyte rheology. AB - Two main subjects of erythrocyte rheology, deformation and aggregation, are discussed in detail, on the basis of biochemical structure. The close relationship between the life span (or cell aging) and the rheology of individual erythrocytes is also briefly described. A currently important problem is emphasized, that is, the molecular aspect of the dynamic cytoskeletal structure and the mechanism of its regulation. This concerns not only the rheological function and the survival of circulating erythrocytes, but also the pathophysiology of abnormal erythrocytes. PMID- 2183813 TI - Bibliography of the current world literature. PMID- 2183814 TI - Multicenter evaluation of a new recombinant enzyme immunoassay for the combined detection of antibody to HIV-1 and HIV-2. AB - A newly developed recombinant antigen-based anti-HIV-1/HIV-2 enzyme immunoassay (Abbott Recombinant HIV-1/HIV-2 EIA) was evaluated against a second generation anti-HIV-1 EIA (Abbott Recombinant HIV-1 EIA). Five thousand and twenty-nine sera from European blood donors and 403 sera from central African blood donors were used in the evaluation, along with four panels and one cohort. The panels included 99 'problem' sera, 733 sera with antibodies to HIV-1 from asymptomatic people and from patients at different disease stages, 25 serial bleeds from five plasmapheresis donors seroconverting for antibodies to HIV-1, and 202 sera with antibodies to HIV-2 collected from healthy and diseased people of European or west African origin. In addition, 734 sera collected from a west African cohort were tested. Using Western blot as the reference standard, the specificity obtained by the recombinant anti-HIV-1 EIA (HIV-i EIA) was 99.90% [99.81-99.99%; 95% confidence limits (95% CL)] with European blood donor sera; 99.50% (98.78 100%) with Central Africa blood donor sera; 92.93% (87.78-98.08%) with 'problem' sera and 99.43% (98.87-100%) with sera from a west African cohort. Using the same samples, the recombinant anti-HIV-1/HIV-2 EIA (HIV-1/HIV-2 EIA) yielded a specificity of 99.84% (99.73-99.95%), 99.50% (98.78-100%), 95.96% (92.00-99.92%) and 98.58% (97.69-99.47%), respectively. All 776 Western blot-confirmed anti-HIV 1 sera were reactive in both EIAs, and the EIA-reactive samples from seroconverting plasma donors were always observed for both assays in the same serial bleed. For HIV-2, the HIV-1 EIA yielded an overall sensitivity of 75.83% (69.93-81.72%) compared with 99.53% (98.58-100%) for HIV-1/HIV-2 EIA. The addition of a recombinant env-protein of HIV-2 to the recombinant env and core proteins of HIV-1 on the solid phase of HIV-1 EIA improved the detection of anti HIV-2 while preserving the assay's overall specificity and sensitivity for the detection of anti-HIV-1. PMID- 2183815 TI - Polyclonal antibodies to mannan from yeast also recognize the carbohydrate structure of gp120 of the AIDS virus: an approach to raise neutralizing antibodies to HIV-1 infection in vitro. AB - This study initiates a new method of developing an antigen which might be useful in the prevention of HIV-1 infection. Using a mannan preparation from Saccharomyces cerevisiae neutralizing antiserum was raised in rabbits which prevents HIV-1 infection in vitro up to a titre of 1:128. The corresponding antibody preparation neutralized the in vitro infectivity down to a concentration of 5 micrograms/ml. Analytical studies suggest that the antibodies are directed against the mannose residues of the HIV-1 glycoprotein (gp) 120 and its precursor gp 160. PMID- 2183816 TI - The epidemic of AIDS and HIV-1 infection among heterosexuals in New York City. PMID- 2183817 TI - Pertussis and pertussis vaccine: 1990. PMID- 2183818 TI - Antimicrobial prophylaxis of pediatric surgical wound infections. PMID- 2183819 TI - Recurrent pneumonia in children. PMID- 2183820 TI - Superficial bacterial and fungal infections of the skin. PMID- 2183821 TI - Campylobacter pylori: a new pathogen. AB - There is now considerable evidence suggesting that C. pylori is a human pathogen. The strong association between C. pylori and gastroduodenal disease is well documented. A number of hypotheses have been suggested for the pathogenic mechanisms of C. pylori-induced gastroduodenal disease, including the production of cytotoxins and the mechanical disruption of the epithelium. At the present time, treatment with a combination of antimicrobial agents eradicates the infection in approximately 50% of cases. Until an ideal therapeutic regimen is available, antimicrobial therapy is recommended only for those patients who continue to be symptomatic following 6 to 8 weeks of treatment with an H2 receptor. PMID- 2183822 TI - Invasive and toxin-mediated Staphylococcus aureus diseases in children. PMID- 2183823 TI - Nonsuppurative complications of group A streptococcal infection. PMID- 2183824 TI - Histotoxicity of cyanoacrylate tissue adhesives. A comparative study. AB - Cyanoacrylate derivatives have been used as surgical adhesives for many years. Shorter-chain derivatives (methyl- and ethyl-cyanoacrylate) have proved to be histotoxic. Longer-chain derivatives (butyl- and isobutyl-cyanoacrylate) are much less histotoxic. Many surgeons continue to use ethyl-2-cyanoacrylate (Krazy Glue) despite the availability of a less toxic derivative, butyl-2-cyanoacrylate (Histoacryl). In this study, the histotoxicity and bone graft-cartilage binding ability of Krazy Glue and Histoacryl were compared. Bone grafts harvested from the anterior wall of the maxillary sinus were placed in a subcutaneous pocket and glued to auricular cartilage in the rabbit. Krazy Glue and Histoacryl were used in opposite ears, harvesting specimens at 1, 2, 4, 12, 24, and 48 weeks. The Krazy Glue-treated ears developed seromas with histologic evidence of acute inflammation, tissue necrosis, and chronic foreign body giant cell reaction. The Histoacryl-treated ears showed mild acute inflammation and mild foreign body giant cell reaction. The Krazy Glue was completely degraded within 12 months, while some Histoacryl was still present at 1 year. Histoacryl had minimal histotoxic effect and good bone graft-cartilage binding ability, whereas Krazy Glue demonstrated severe histotoxicity. PMID- 2183825 TI - The efficacy of cefaclor vs amoxicillin on recovery after tonsillectomy in children. AB - Tonsillectomy and adenoidectomy continues to be one of the most commonly performed operations in the pediatric age group. The morbidity from tonsillectomy can be severe and includes throat and ear pain, fever, lethargy, and poor oral intake. A previous study at the Children's Hospital of Philadelphia (Pa) demonstrated the efficacy of amoxicillin therapy in minimizing some of these postoperative symptoms. However, some children continue to have a prolonged recovery even while receiving this antibiotic regimen. Because of these children and the high incidence of Staphylococcus found in tonsillar core tissue, a randomized, prospective study was undertaken at the Children's Hospital of Philadelphia to evaluate the efficacy of cefaclor vs amoxicillin in patients recovering from tonsillectomy. The patients received either ampicillin or cefazolin intravenously at the time of surgery and for 12 to 24 hours postoperatively. When oral intake was adequate, they received either amoxicillin or cefaclor orally for 7 additional postoperative days. Intraoperative cultures of the oropharynx and tonsillar tissue were obtained, as well as cultures of the tonsillar fossa 7 to 14 days postoperatively. The patients were evaluated for severity and duration of postoperative symptoms as well as complications. The results of this study showed no difference between the two groups of patients. We conclude that there is no justification for routine use of cefaclor over amoxicillin in the posttonsillectomy patient. PMID- 2183826 TI - Recurrent meningitis and Mondini dysplasia. AB - Three infants with cerebrospinal fluid otorrhea and recurrent meningitis due to Mondini dysplasia have been treated at Baylor College of Medicine, Houston, Tex; 39 other patients with this association have been described. This review highlights the characteristics and embryologic basis of the malformation. The clinical evaluation of an infant with recurrent meningitis is outlined, and the importance of brain-stem response audiometry and thin-cut computed tomography of the temporal bones is discussed. Surgical management depends on the functional status of the dysplastic ear; usually, a stapedectomy is performed and the vestibule is obliterated. Although the surgical failure rate is 30% after one procedure, early identification of the dysplasia and prompt surgical management diminish morbidity and mortality and permit early habilitation of the child with congenital hearing impairment. PMID- 2183827 TI - The diagnostic dilemma of otosyphilis. A new western blot assay. AB - Currently, the diagnosis of otosyphilis applies to any patient with otologic symptoms of unknown cause and a positive fluorescent treponemal antibody absorption (FTA-ABS) test result. However, the FTA-ABS assay can have false positive results and does not distinguish between active and treated disease. The VDRL test, which has been used to distinguish inactive disease, frequently yields negative results in patients who are nonetheless given the diagnosis of otosyphilis. A new Western blot assay can eliminate the possibility of a false positive result and can confirm whether the infection is active. This assay was used to diagnose unsuspected active syphilis in a patient believed to have autoimmune ear disease. In three other cases of suspected otosyphilis, the diagnosis was refuted when the Western blot demonstrated that the FTA-ABS result was false-positive or that the infection was inactive. PMID- 2183828 TI - Antibiotics for secretory otitis media. PMID- 2183829 TI - Strategies for testing the "irritation-signaling" model for chronic lung effects of fine acid particles. AB - The "irritation signaling" model proposed that a long term contribution to chronic bronchitis might result from the repeated delivery of "signals" resulting from temporary localized acidification of the bronchial epithelium by the action of individual particles. This led to a prediction that the effectiveness of particles in inducing changes in mucus secreting cell numbers/types should depend on the number of particles deposited that contained a particular amount of acid- implying that particles below a certain size cutoff (and therefore lacking a minimum amount of acid) should be ineffective; and that particle potency per unit weight should be greatest at the cutoff and decline strongly above the cutoff. Since the development of this hypothesis both epidemiological observations and some experimental studies have tended to reinforce the notion that acid particles can make a contribution to relatively long lasting bronchitic-like changes, and enhance the desirability of more direct testing of the model. In this paper we develop a general theoretical framework for the contributions of environmental agents to chronic obstructive lung disease, and a series of alternative hypotheses against which the predictions of the "irritant signaling" model can be compared. Based on this, we suggest a research program that could be used to further develop and test the model and reasonable alternatives. PMID- 2183830 TI - Cytological effects of the microinjection of antibody to ras p21 in early cleavage Xenopus embryos. AB - The presence of two ras-related proteins (22 and 23 kDa) was demonstrated in Xenopus embryonic extracts by selective immunoprecipitation using anti-ras monoclonal antibodies 142-24E05 and Y13-259. We further describe the cytological effects of the microinjection of anti-ras monoclonal antibody Y13-259 into early cleavage blastomeres of Xenopus embryos. Injection of the antibody into a blastomere at the two-, four-, or eight-cell stage caused cleavage arrest in the descendants of the injected blastomere. Light microscopy (LM) of cleavage arrested cells revealed extensive deformation of the cells as well as heterogeneity of distribution of yolk platelets and pigment granules. LM analysis of serial sections of cleavage-arrested cells revealed the presence of multiple nuclei. Although the nuclei expressed similar morphological properties, indicating that they were probably in the same stage of the nuclear cycle, they revealed highly variable chromatin densities. Electron microscope (EM) analysis of the cytoplasm of cleavage-arrested cells revealed the accumulation of vesicles and large membranous elements coincident with cleavage arrest. Furthermore, endoplasmic reticulum (ER) existed in two forms, as closed, circular profiles and as long, linear arrays. Mitochondria were characteristically aligned in single file on both sides of the two types of ER cisternae. EM analysis of nuclei confirmed variations in chromatin organization and suggested the occurrence of unique nuclear envelope fusion among micronuclei in cleavage-arrested cells. Cleavage arrest and changes in cytological features were not observed in the cytoplasm of cells microinjected with normal rat IgG. Thus the immunochemical data and microinjection experiments suggest that ras-like or ras antigenicity exists within rapidly replicating Xenopus blastomeres and may be involved in the organization of a number of its cytoplasmic elements. PMID- 2183831 TI - Production and characterization of monoclonal antibodies to the mammalian sperm cytoskeleton. AB - The cytoskeleton exerts a direct effect on the function of sperm by influencing the distribution of subcellular organelles and plasma membrane molecules. We have prepared six monoclonal antibodies to Triton X-100-insoluble components of the bull sperm cytoskeleton. One of the antibodies reacts with a detachable portion of the bull sperm acrosome. The remainder include an antibody that recognizes the principal and end piece of the tail and another that is specific to the middle piece. Two of the antibodies yield dissimilar staining patterns of the neck region and the tail, and the final monoclonal antibody stains the subacrosomal region and a detachable acrosomal domain of bull sperm. The cross reactivities of the antibodies with hamster sperm and PtK2 cells are described, as is the recognition of bull sperm polypeptides on western blots. The results suggest that these antibodies will provide interesting insights concerning the role of the cytoskeleton in sperm development and function. PMID- 2183832 TI - Effects of gossypol on the motility of mammalian sperm. AB - The effects of the male contraceptive gossypol on the motility of mammalian spermatozoa are reviewed. The role of sperm motility in the processes of fertilization and the effect of the drug on these processes determine its effectiveness as a contraceptive. The promising male contraceptive potential of gossypol is discussed in the context of the serious adverse effects of the agent. PMID- 2183833 TI - Associations between microtubules and intracellular organelles. PMID- 2183834 TI - The cytoskeleton of Saccharomyces cerevisiae. PMID- 2183835 TI - Molecular genetics: a key to the cytoskeleton's closet. PMID- 2183836 TI - Stem cell biology, hormone/matrix synergies and liver differentiation. AB - Extracellular matrix, in conjunction with hormones and growth factors, plays a profound role in regulating gene expression in liver and in all tissues. The availability of matrix components for liver cells in culture is having a major impact on our ability to study every aspect of gene expression. Its significance has been particularly profound in permitting cultures with partial restoration of transcription rates of tissue-specific mRNAs. However, the matrix reagents available to date are not so potent as the forms known to be present uniquely in the liver. Thus, there is a great need to purify and characterize these tissue specific matrix components (e.g. heparin-PG) to enable the eventual production of them for general use by investigators. The use of matrix reagents and the eventual use of cultures of liver stem cells will begin a new era in the understanding of liver differentiation. PMID- 2183837 TI - Bibliography of the current world literature. Cytoplasm and cell motility. PMID- 2183838 TI - Functional properties of kinetochores in animal cells. PMID- 2183839 TI - Genetics and biochemistry of centrosomes and spindle poles. PMID- 2183840 TI - Microtubular structure and tubulin polymerization. PMID- 2183841 TI - Actin. PMID- 2183842 TI - Spectrin: a structural mediator between diverse plasma membrane proteins and the cytoplasm. AB - The spectrin skeleton of non-erythroid cells is likely to interact with a variety of integral membrane proteins and participate both in stable linkages as well as dynamic structures capable of rapid disassembly and assembly. The basis for diversity of roles for spectrin includes multiple, functionally distinct isoforms of spectrin, ankyrin and other associated proteins, regulation of protein interactions through phosphorylation and calcium/calmodulin, as well as differential expression of accessory proteins that determine the organization and localization of spectrin in cells. Spectrin is highly conserved from Drosophila to man and is likely to be involved in fundamental aspects of membrane structure requiring long range order and organization. Spectrin is a candidate to interact with many integral membrane proteins in roles basic to metazoan cells which must associate into tissues. Organization of cells into tissues requires loss of cell motility, formation of specialized membrane domains and assembly of cell junctions, which are all activities potentially involving spectrin. Future challenges lie in devising direct experiments to evaluate the functions of spectrin in cells and tissues. PMID- 2183843 TI - Myosin I. PMID- 2183844 TI - Force generation in muscle. PMID- 2183845 TI - Cell migration in the embryo and adult organism. PMID- 2183846 TI - Cytoskeleton and embryo polarity. PMID- 2183847 TI - Intermediate filaments: structure, assembly and molecular interactions. PMID- 2183848 TI - The neutrophil and leukotrienes--role in health and disease. AB - The granulocyte plays a major role in inflammatory processes by its capability to produce and release proinflammatory mediators such as the leukotrienes. This class of mediators exerts multiple functions in various physiological and pathophysiological processes. The interdependent interaction among the various mediator cascades, the inflammatory cells as well as the neuroendocrine system are areas of current interest. Appropriate stimuli (immunological, non immunological) by their defined pattern of signal transduction are responsible for priming, cellular activation and deactivation of granulocytes as it is shown for microbial infection. Thus the mediators may provide the prerequisites for a balanced homeostasis during host defense. It is clear that among the complexity of mediators not a single factor but the interaction of multiple mediator cascades reflect the final outcome of the disease process. In this regard the actual concentrations at local sites are obviously more relevant as those in whole body fluids. PMID- 2183849 TI - [Arterial hypertension associated with hyperlipoproteinemia]. AB - Hypertension and serum cholesterol levels are strongly interrelated as cardiovascular risk factors. The Framingham study showed that the risk of both ischaemic heart disease and brain infarction doubles in presence of mild hypertensive status and triplicates in presence of a definitive hypertension. The systolic pressure showed to be the best predictor of both ischaemic heart disease and cerebral infarction particularly in persons aged more than 65 years. In terms of physiopathology we point out several mechanisms by which hypertension could interact with hypercholesterolemia on the arterial wall causing endothelial lesion, enhancing the penetration of arterial wall by lipoproteins, calcium accumulation on smooth subendothelial muscle and suppression of the relaxation factor produced by endothelial cells. In relation to the dietetic treatment, we must restrict more rigorously the ingestion of salt, saturated fatty acids, and total calories. In terms of anti-hypertensive drugs, we should: Avoid thiazide diuretics in case of cholesterol levels of moderate to high risk. Avoid beta blockers in patients with high levels of triglycerides, low HDL and low ratio total cholesterol/HDL. Consider to choose a calcium antagonist, a converting enzyme or an alpha blocker. PMID- 2183850 TI - A rapid screen for the detection of specific DNA sequences in plants. AB - We have developed a simple and quick method ("wick blot") for detecting the presence of specific DNA sequences in plants, using radiolabeled DNA probes. The method requires only small amounts of tissue, about 15-25 mg. More than a hundred samples per day can be easily extracted and blotted. It works well on various species and tissues, including leaves, embryos, and callus. The method is ideally suited for screening large numbers of putative transformants, especially populations that have not been screened by prior selection. PMID- 2183851 TI - Affinity purification of specific DNA fragments using a lac repressor fusion protein. AB - A new method for purification of specific DNA sequences using a solid phase technique has been developed based on a fusion between the Escherichia coli lac repressor gene (lacI) and the staphylococcal protein A gene (spa). The fusion protein, expressed in Escherichia coli, is active both in vivo and in vitro with respect to its three functional activities (DNA binding, IPTG induction, and IgG binding). The recombinant protein can be immobilized in a one-step procedure with high yield and purity using the specific interaction between protein A and the Fc part of immunoglobulin G. The immobilized repressor can thereafter be used for affinity purification of specific DNA fragments containing the lac operator (lacO) sequence. PMID- 2183852 TI - A cluster of central nervous system defects in Jamaica. AB - 1. Information was collected on all stillbirths and neonatal deaths on the island of Jamaica during the 12-month period between September 1986 and August 1987. 2. There were 33 such deaths with anencephaly, spina bifida and hydrocephalus out of an estimated 54,400 total births. 3. There was a statistically significant cluster in respect to time of conception in one small rural area of the island. 4. There were no obvious differences between parents involved in the cluster and the rest of the population, but particular Jamaican fruit and vegetables have been shown to be teratogenic in animals. It is postulated that the cluster may have been associated with an unripe crop. PMID- 2183853 TI - Novel vaccination and antireceptor strategies against HIV. PMID- 2183854 TI - Protease activation during HIV infection in a CD4-positive cell line. AB - The mechanism of cytopathic effects associated with HIV infection in a continuous line of CD4-positive lymphocytes (CEM cells, clone 13) has been studied. Here we report the following observations: (1) HIV infection killed a variable but always significant number of cells without a strict relationship with the syncytia formation; (2) an important decrease in the proliferation rate occurred soon after infection; (3) a marked inhibition of protein synthesis took place within the first few hours of infection and clearly before the beginning of viral protein expression. In addition, when three-day-old cultures were incubated in serum-free medium, a larger degradation of proteins was observed in infected cells in comparison to controls. An increase in protein degradation activity was observed also in vitro with extracts obtained from HIV-infected cells and incubated in the presence of endogenous- or exogenous-labeled substrates. Extracts from cells infected with heat-inactivated HIV did not show a similar degradative activity. The possible induction or activation of latent proteases during the development of the HIV infection is discussed. PMID- 2183855 TI - Selected nonpharmacological therapies for chronic pain: the therapeutic use of the placebo effect. AB - Chronic pain is a common problem requiring a multidisciplinary approach. Nursing can offer diverse therapies complementary to the medical-surgical approach. Guidelines for practice and challenges for research are outlined for selected nonpharmacological chronic pain therapies. This article discusses the placebo effect, which is common to all therapies. Placebos can therapeutically empower patients to stimulate their psychophysiologic self-regulation abilities. Effects, theories, ethics, and therapeutic methods of stimulating the placebo effect are explored. PMID- 2183856 TI - Electrical neurostimulators for pain relief in angina. PMID- 2183857 TI - Cardiac defects in the children of mothers with high concentrations of plasma phenylalanine. PMID- 2183858 TI - What is meant by a "controlled" ventricular rate in atrial fibrillation? AB - Reduction of a rapid ventricular rate in atrial fibrillation results in a longer diastolic filling period and a higher left ventricular stroke volume but this is offset by reduced contractility and fewer beats per minute; the net effect on cardiac output is uncertain. Sequences of stroke distances were measured by Doppler ultrasound in 60 resting patients with atrial fibrillation to determine the relation between ventricular rate and linear cardiac output. The slope of the cardiac output/ventricular rate relation was positive in all 20 patients with a ventricular rate less than 90 beats per minute and negative in 16 (40%) of 40 patients with a ventricular rate greater than 90 beats per minute. In atrial fibrillation the ventricular rate can be regarded as "controlled" when the cardiac output/ventricular rate slope is positive and "uncontrolled" when the slope is negative--that is when reduction of ventricular rate would lead to increased cardiac output. As so defined, ventricular rate at rest was controlled in every patient when the ventricular rate was less than 90, controlled in 44 (73%) patients when the ventricular rate was 90-140 beats per minute, and uncontrolled in every case when it was greater than 140 beats per minute. Achieving a target ventricular rate of 90 beats per minute in patients with atrial fibrillation at rest would result in control with the least compromise of cardiac output. PMID- 2183859 TI - Range of atrioventricular conduction disturbances in Lyme borreliosis: a report of four cases and review of other published reports. AB - Four patients with Lyme borreliosis had atrioventricular conduction disturbances. All four were positive for specific antibodies against Borrelia burgdorferi measured by indirect immunofluorescence tests. Biopsy specimens, which were obtained in three patients, showed band-like infiltrates of plasma cells and lymphocytes in the endocardium. There was diffuse infiltration of the interstitium of the myocardium by lymphocytes, plasma cells, and macrophages. In two patients single fibre necrosis was seen in the myocardium. Biopsy specimens of the heart showed spirochetes in all three patients and serial sections stained by the Bosma-Steiner technique showed that they resembled Borrelia burgdorferi. At follow up one patient had persistent complete atrioventricular block, despite treatment with antibiotics and corticosteroid, and a permanent pacemaker was implanted. PMID- 2183860 TI - Limitations of Doppler ultrasound in the assessment of the function of prosthetic mitral valves. AB - Pressure half time has been assumed to be a relatively flow-independent measure of orifice area, but it may also be influenced by atrial and ventricular factors. Pressure half time and peak left ventricular inflow velocity were measured by continuous wave Doppler ultrasound in 164 patients with normally functioning Carpentier-Edwards, Bjork-Shiley, and Starr-Edwards mitral prostheses. Pressure half time was shorter in the Bjork-Shiley than in the other value types and peak transmitral velocity was highest in the Starr-Edwards prostheses. These differences, however, were partly explained by coexistent differences in transmitral flow. Filling time accounted for 19% and stroke volume for 15% of the variance in pressure half time compared with only 5.6% for prosthetic design and 0.4% for annulus diameter when each of these variables was considered alone. The design of the prosthesis explained 18% of the variance in peak transmitral velocity, while cardiac output and annulus diameter did not contribute significantly. With Doppler ultrasound it is impossible to define reliable normal ranges for prosthetic function independently of atrial and ventricular function. Formulas for orifice area based on peak transmitral velocity and flow seem more likely to reflect the behaviour of normally functioning prostheses than those based on pressure half time. PMID- 2183861 TI - Bernard A Robinson 1888-1979: an unknown pioneer of electrocardiography. PMID- 2183862 TI - An international consensus on monitoring? PMID- 2183863 TI - Body temperature and anaesthesia. PMID- 2183864 TI - Analgesia following extradural and i.m. pethidine in post-caesarean section patients. AB - The onset, quality and duration of analgesia following extradural pethidine 50 mg and i.m. pethidine 100 mg was assessed in 30 postoperative patients who had undergone Caesarean section under extradural anaesthesia. Saline and pethidine were given in a randomized, double-blind fashion using simultaneous extradural and i.m. injections. Extradural pethidine provided superior analgesia, of quicker onset but similar duration, and both treatments were associated with a low incidence of side effects. PMID- 2183865 TI - Deja vu. PMID- 2183866 TI - The comparative effects of paracetamol and indomethacin on renal function in healthy female volunteers. AB - 1. Renal function was assessed in 10 healthy female volunteers during administration of placebo, paracetamol (acetaminophen) (4.0 g daily) and indomethacin (150 mg daily) for 3 days under conditions of controlled sodium and fluid intake. 2. Paracetamol and indomethacin had no significant effect on the glomerular filtration rate and effective renal plasma flow as measured by the renal clearances of inulin, creatinine and p-aminohippurate (PAH). 3. Compared with placebo, paracetamol reduced the mean urinary excretion of prostaglandin E2 by 43% on the second day and 58% on the third treatment day (P less than 0.01). With indomethacin the corresponding reductions were 73 and 80%. Paracetamol and indomethacin had much less effect on the excretion of prostaglandin 6-keto F1 alpha, and a significant decrease was observed only on the third day. 4. The decreased urinary excretion of prostaglandin E2, produced by paracetamol was associated with a reduction in sodium excretion of more than 50% (P less than 0.01) and delay in the onset of diuresis following an acute water load. 5. The renal effects of paracetamol and indomethacin appear to differ. Although indomethacin reduced prostaglandin excretion more than paracetamol it had a similar effect on sodium excretion and less initial antidiuretic action. Unlike paracetamol, indomethacin also reduced basal plasma renin activity. 6. Paracetamol reduced the total body clearance of PAH and increased its plasma half life. This effect could be attributed to inhibition of the acetylation of PAH by paracetamol. 7. In normal use paracetamol does not appear to have the adverse renal effects associated with the non-steroidal anti-inflammatory analgesics and further studies are required to establish the clinical significance of these findings. PMID- 2183867 TI - Plasma protein binding of disopyramide in pregnant and postpartum women, and in neonates and their mothers. AB - 1. The protein binding of disopyramide was measured in plasma obtained from nonpregnant women, pregnant women in the first, second, and third trimesters, matched pairs of mothers and neonates (cord plasma), and 1 month postpartum women (n = 6 or 8 of each). 2. Plasma samples spiked with 0.2-12.0 micrograms ml-1 of the drug were ultrafiltered and the free fractions were measured with a fluorescent polarization immunoassay. 3. The mean (+/- s.d.) percentages of free drug at a total concentration of 3.0 micrograms ml-1 observed in the third trimester (46 +/- 9%) and neonate (79 +/- 5%) groups were greater (P less than 0.05 or 0.01) than that in the non-pregnant group (34 +/- 7%). In contrast, the corresponding value observed in the postpartum group (23 +/- 8%) was less (P less than 0.05) than that in the non-pregnant group. In addition, there was a significant (P less than 0.01) difference in the mean percentage of free drug at 3.0 micrograms ml-1 in plasma from mothers (43 +/- 9%) and neonates (79 +/- 5%). 4. A multiple regression analysis indicated that alpha 1-acid glycoprotein (r = 0.88, P less than 0.01), rather than albumin (r = -0.008), dominated the binding of disopyramide within the therapeutic range of drug concentration. An analysis of the binding parameters of disopyramide suggested that alterations in binding were attributable to changes in the capacity rather than the affinity of binding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2183868 TI - Comparison of once daily atenolol, nitrendipine and their combination in mild to moderate essential hypertension. AB - 1. The aim of the study was to compare the efficacy and the tolerability of treatment with atenolol (50-100 mg once daily), nitrendipine (20-40 mg once daily) and their combination (atenolol 50 mg + nitrendipine 20 mg) once daily in patients with mild to moderate essential hypertension. 2. The study was a randomised, double-blind, placebo controlled parallel groups design: blood pressures were measured at 'trough' effect (i.e. 24 h after dosing) to assess the adequacy of once-daily treatment. 3. Mean blood pressures (mm Hg) recorded on four occasions over 12 weeks of treatment were significantly lower both with atenolol (155/97 sitting: 155/104 standing) and with the combination of atenolol plus nitrendipine (153/96 sitting: 152/104 standing) than with placebo (169/108 sitting: 169/114 standing). Nitrendipine alone had no significant effect on blood pressure 24 h after dosing (165/104 sitting: 165/110 standing). 4. Withdrawals due to adverse effects were more common during treatment with nitrendipine: 7/32 of the patients experienced adverse effects attributable to intense systemic vasodilatation (e.g., flushing, erythema, headache). 2/37 patients taking atenolol were withdrawn: one because he developed a psoriatic rash and the other because of impaired peripheral circulation. Of the 35 patients taking combination treatment, two were withdrawn: one developed headaches and dyspnoea, and the other asthma. 5. The results suggest that once daily dosing with nitrendipine does not control blood pressure throughout the 24 h period in the majority of patients, and is associated with a considerable burden of adverse effects. Combination treatment was better tolerated but appeared to offer no advantages over atenolol alone in terms either of blood pressure control or adverse effects. PMID- 2183869 TI - Anti-emetics and cancer chemotherapy. PMID- 2183870 TI - Where next with therapy in advanced neuroblastoma? PMID- 2183871 TI - Tumour necrosis factor: a cytokine with multiple biological activities. PMID- 2183872 TI - Low incidence of ras oncogene activation in human squamous cell carcinomas. AB - Activation of the ras gene family by point mutation at codons 12, 13 and 61 has been demonstrated in up to 20% of unselected series of human tumours. The present study was carried out to assess the incidence of ras activation in 37 squamous cell carcinomas of the head and neck, seven squamous cell carcinomas of the skin and eight squamous carcinoma cell lines. Oligonucleotide probes and the polymerase chain reaction were used on DNA extracted from achival paraffin embedded material. Mutations in codon 12 of the Harvey ras gene was found in a carcinoma of the larynx and a carcinoma of the lip, both of which had received prior irradiation. A cell line (LICR-LON-HN8) established from the same laryngeal cancer showed the same mutation. This study indicates that there is a low incidence of ras mutation in human squamous cell carcinomas and that activation of this family of genes is probably not a common factor in the development of this group of tumours. PMID- 2183873 TI - A phase I and pharmacokinetic study of didox administered by 36 hour infusion. The Cancer Research Campaign Phase I/II Clinical Trials Committee. AB - Twelve patients were treated with didox, a new ribonucleotide reductase inhibitor, by 36 h infusion. The maximum tolerated dose was 6 g m-2, above which dose-limiting hepatic toxicity was observed. Patient tolerance was significantly better using the 36 h infusion compared to patients receiving the drug by a 30 min infusion; in particular, there were no reports of nausea or vomiting. No responses were seen in these patients. Detailed pharmacokinetics were performed at 6 g m-2 comparing the 36 h and 30 min infusions in four patients. Parent drug AUC values were lower for the 36 h infusion, 67.8 micrograms ml-1 h-1 compared to 232 micrograms ml-1 h-1 for the 30 min infusion. AUC values for the 3-hydroxy metabolite were much higher following the 36 h infusion: 55.4 compared to 18.6 micrograms ml-1 h-1. In contrast, the amide metabolite was not detected following the 36 h infusion, but AUC values of 23 micrograms ml-1 h-1 were seen after the 30 min infusion. The mean peak plasma level was 72 micrograms ml-1 following 6 g m-2 given by a 30 min infusion compared to 2.8 micrograms ml-1 following the prolonged infusion. Clearance was higher following the 36 h infusion: 97.6 versus 24.4 l h-1. PMID- 2183874 TI - Pharmacokinetics of carboplatin at a dose of 750 mg m-2 divided over three consecutive days. AB - Pharmacokinetics of the cisplatin analogue carboplatin were studied in patients with disseminated ovarian and testicular cancer. Carboplatin 750 mg m-2 divided over three consecutive days was given as part of an ablative combination regimen followed by autologous bone marrow transplantation. Platinum (Pt) in plasma, plasma ultrafiltrate and urine was determined up to 96 h after the last drug dose by atomic absorption spectrometry. Carboplatin was measured by high performance liquid chromatography. The curves of ultrafiltrated Pt and carboplatin decayed in a bio-exponential way with t1/2 alpha of respectively 65 and 70 min and t1/2 beta of respectively 378 and 1014 min. The volumes of distribution (Vdss) were 18 and 25 l m-2, respectively, and total body clearances (ClTB) 79 and 65 ml min-1 m-2. Both curves overlapped when corrected for the Pt content of carboplatin. A diversion with the three-exponential curve of total Pt occurred between 3 and 6 h. After 10 h approximately 30% of the plasma Pt was protein bound. Total Pt had a larger Vdss (117 l m-2) and a lower total body clearance (14 ml min-1 m-2) than free Pt and carboplatin. Fifty-three per cent of the i.v. administered carboplatin was excreted in the urine in the first 6 h. Plasma ultrafiltrated Pt and carboplatin decreased to undetectable levels within 48 h, but total Pt was detectable until 96 h after the last carboplatin dose. However, this Pt is already bound to protein and unlikely to be cytotoxic to reinfused haemopoietic stem cells, so bone marrow reinfusion can be safely performed at 48 h after repeated dosing of carboplatin on three consecutive days. PMID- 2183875 TI - A multicentre mortality study of workers exposed to ethylene oxide. AB - A multicentre cohort study was carried out to study the possible association between exposure to ethylene oxide and cancer mortality. The cohort consisted of 2658 men from eight chemical plants of six chemical companies in the Federal Republic of Germany who had been exposed to ethylene oxide for at least one year between 1928 and 1981. The number of subjects in the separate plants varied from 98 to 604. By the closing date of the study (31 December 1982) 268 had died, 68 from malignant neoplasms. For 63 employees who had left the plant (2.4%) the vital status remained unknown. The standardised mortality ratio for all causes of death was 0.87 and for all malignancies 0.97 compared with national rates. When local state rates were used the SMRs were slightly lower. Two deaths from leukaemia were observed compared with 2.35 expected (SMR = 0.85). SMRs for carcinoma of the oesophagus (2.0) and carcinoma of the stomach (1.38) were raised but not significantly. In one plant an internal "control group" was selected matched for age, sex, and date of entry into the factory and compared with the exposed group. In both groups a "healthy worker effect" was observed. The total mortality and mortality from malignant neoplasms was higher in the exposed than in the control group; the differences were not statistically significant. There were no deaths from leukaemia in the exposed group and one in the control group. PMID- 2183876 TI - Delpech and the origins of occupational psychiatry. AB - Auguste-Louis Delpech (1818-80) has been remembered principally as the author of the first detailed description of the serious consequences of exposure to carbon disulphide. A close reading of his work suggests that his reputation has been seriously undervalued. The subsequent development of occupational psychiatry, with its emphasis on the distinction between the organic and the functional, may be traced through publications on carbon disulphide. It is argued that a contemporary approach to occupational psychiatry is long overdue. PMID- 2183877 TI - Role of diffusion in the folding of the alpha subunit of tryptophan synthase from Escherichia coli. AB - The rate-limiting step in the folding of the alpha subunit of tryptophan synthase has been proposed to be the association of two folding units. To probe the role of diffusion in this rate-limiting step, the urea-induced unfolding and refolding of the protein was examined in the presence of a number of viscosity-enhancing agents. The analysis was simplified by studying the effect of these agents on folding unit dissociation, the rate-limiting unfolding reaction, and the reverse of the rate-limiting step in refolding. In the presence of ethylene glycol, the relaxation times for unfolding to the same final conditions increased with increasing concentration of the cosolvent. When the effects of the cosolvent on protein stability were taken into account, the rates were found to show a unitary linear dependence on the viscosity of the solution. Similar results were obtained with glycerol and low concentrations of glucose, demonstrating that the effect is general and not specific to any viscogenic agent. These results clearly demonstrate that the rate-limiting folding unit association/dissociation reaction in the alpha subunit of tryptophan synthase involves a diffusional process. PMID- 2183878 TI - Na+ participates in loop diuretic-sensitive Cl(-)-cation co-transport in the pancreatic beta-cells. AB - In order to investigate whether Na+ participates in loop diuretic-sensitive Cl(-) cation co-transport in the beta-cells, we tested the interaction between the effects of Na+ deficiency, furosemide and D-glucose on 86Rb+ fluxes in beta-cell rich mouse pancreatic islets. Removal of extracellular Na+ slightly reduced the ouabain-resistant 86Rb+ influx and the specific effect of 1 mM furosemide on this influx was significantly smaller in Na(+)-deficient medium. The capacity of 20 mM D-glucose to reduce the ouabain-resistant 86Rb+ influx was not changed by removal of extracellular Na+. The 86Rb+ efflux from preloaded islets was rapidly and reversibly reduced by Na+ deficiency. Furosemide (1 mM) reduced the 86Rb+ efflux and the effect of the combination of Na+ deficiency and 1 mM furosemide was not stronger than the effect of furosemide alone. 22Na+ efflux was reduced by both ouabain and furosemide and the effects appeared to be additive. The data suggest that Na+ participates in loop diuretic-sensitive Cl(-)-cation co-transport in the pancreatic beta-cells. This adds further support to the idea that beta-cells exhibit a Na+, K+, Cl- co-transport system. Since some of the furosemide effect on 86Rb+ efflux persisted in the Na(+)-deficient medium, it is likely that also loop diuretic-sensitive K+, Cl- co-transport exists in this cell type. PMID- 2183879 TI - Growth hormone response to intravenous diazepam and placebo in 82 healthy men. AB - Growth hormone (GH) response to placebo and two different doses of diazepam (0.12 mg/kg and 0.20 mg/kg) were evaluated in 82 healthy young men. Both diazepam doses had a significant effect on the growth hormone secretion, with peak values occurring between 30 and 60 min postinfusion, after which levels returned to baseline. There was also a small but significant change in this hormone over time after placebo, but this was reflected by a slow rise following the saline infusion. Individual GH responses to diazepam were variable and, when a cut-off point of 7.5 ng/ml GH increase before 90 min postdrug administration was used, 1% of the men demonstrated a response after placebo, 17% after low-dose diazepam, and 37% following high-dose diazepam. The clinical implications and limitations of these findings are discussed. PMID- 2183880 TI - Quantitative, waking EEG research on depression. AB - Research published in the past decade that used quantitative indices to evaluate the waking EEG characteristics of depressed patients is reviewed. Methodological problems that make results of different research laboratories difficult to compare include diagnostic heterogeneity of depressed groups, lack of inclusion of control subjects, and differences in the EEG techniques. Despite interpretive problems that arise from such substantial variation, consistencies nevertheless emerge. Unmedicated, actively depressed patients appear to exhibit elevated EEG alpha and beta compared to control subjects. Delta and theta distinguished depressed patients from controls in some single studies, but variation in age, specific diagnostic depression categories, and EEG acquisition and analysis techniques rendered these results less definitive. Quantitative EEG differences that may distinguish depressed subject samples from those with other psychiatric disorders are considered. Factors that limit comparability of the findings are discussed in conjunction with strategies that deserve systematic study in future research. PMID- 2183881 TI - Comparison of enalapril and captopril in the management of self-induced water intoxication. PMID- 2183882 TI - Applications of graph theory to enzyme kinetics and protein folding kinetics. Steady and non-steady-state systems. AB - Graphic methods have proved to be very useful in enzyme kinetics, as reflected in both raising the efficiency of performing calculations and aiding in the analysis of catalytic mechanisms. The kinetic relations among protein folding states are very similar to those between enzyme-catalyzed species. Therefore, it should be equally useful to provide a visually intuitive relation between kinetic calculations and folding mechanisms for protein folding kinetics, as manifested by the graphic rules in enzyme kinetics. It can actually be anticipated that, due to increasing interest in protein folding, the graphic method will become an important tool in folding kinetics as well. Based on the recent progress made in graphic methods of enzyme kinetics, in this review four graphic rules are summarized, which can be used to deal with protein folding systems as well as enzyme-catalyzed systems. Rules 1-3 are established for deriving the kinetic equations for steady-state processes and Rule 4 for those in the case of non steady-state processes. In comparison with conventional graphic methods, which can only be applied to a steady-state system, the current rules have the following advantages: (1) Complicated and tedious calculations can be greatly simplified. (2) A lot of wasted labor can be turned away. (3) Final results can be double-checked by a formula provided in each of the graphic rules. (4) Transient kinetic systems can also be treated. The mathematical proof of Rules 1 4 is given in appendices A-D, respectively. PMID- 2183883 TI - A comparative analysis of single- and multiple-residue substitutions in the alkaline phosphatase signal peptide. AB - The alkaline phosphatase signal peptide participates in transport of the enzyme to the periplasmic space of Escherichia coli. The signal sequence, like that of other signal peptides, is composed of a polar amino-terminal segment, a central region rich in hydrophobic residues and a carboxy-terminal region recognized by signal peptidase. We have previously shown that an alkaline phosphatase signal peptide mutant containing a polyleucine core region functions efficiently in transport of the enzyme [D. A. Kendall, S. C. Bock, and E. T. Kaiser (1986) Nature 321, 706-708]. In this study, some of the amino acid changes involved in the polyleucine sequence are examined individually. A Phe to Leu substitution as the sole change results in impaired transport properties in contrast to when it is combined with three other amino acid changes in the polyleucine-containing sequence. A mutant with a Pro to Leu substitution in the hydrophobic core region is comparable to wild type while the same type of substitution (Pro to Leu) in the carboxy-terminal segment results in substantial accumulation of the mutant precursor. Finally, introduction of a basic residue into the hydrophobic segment (Leu to Arg substitution) results in a complete export block. These results exemplify the spectrum of properties produced by individual residue changes and suggest there is some interplay between hydrophobicity and conformation for signal peptide function. PMID- 2183884 TI - Effect of nifedipine on antipyrine and theophylline disposition. AB - On the basis of reports that some calcium channel blockers impair the elimination of some drugs, the effect of nifedipine on the disposition of antipyrine and theophylline was assessed in healthy volunteers. Antipyrine half-life of 10.04 +/ 1.43 h (mean +/- SD) after a week intake of nifedipine (20 mg twice daily) was not significantly different from the control value of 10.64 +/- 2.15 h; nor was that of 10.02 +/- 1.49 h after 2 weeks pretreatment with the calcium channel blocker in eight healthy volunteers. Control antipyrine clearance (ml min-1) of 44.40 +/- 10.58 was not significantly different from that of 45.66 +/- 9.34 and 46.87 +/- 9.63 after nifedipine pretreatment of 1 and 2 weeks, respectively. Similarly volume of distribution was unaltered: 0.601 +/- 0.074, 0.591 +/- 0.078 and 0.602 +/- 0.051 l kg-1, respectively. A week pretreatment with nifedipine did not significantly alter either of theophylline half-life (7.32 +/- 0.81 h (control) to 7.50 +/- 0.80 h) or clearance (42.10 +/- 5.84 ml min-1 (control) to 43.77 +/- 4.00 ml min-1) in six volunteers. However the change in volume of distribution: 0.451 +/- 0.053 l kg-1 (control) to 0.483 +/- 0.062 l kg-1 was significant (p less than 0.025). Generally, theophylline plasma levels were lower after nifedipine pretreatment and the difference was significant at 2 and 4 h post-dosing (p less than 0.05). It is suggested that nifedipine, unlike diltiazem and verapamil, is unlikely to interfere with the functional integrity of the hepatic mixed-function oxygenase enzymes, but might displace theophylline from plasma protein. PMID- 2183885 TI - Phosphatidylinositol-linked proteins and paroxysmal nocturnal hemoglobinuria. PMID- 2183886 TI - Recombinant tumor necrosis factor enhances the proliferative responsiveness of murine peripheral macrophages to macrophage colony-stimulating factor but inhibits their proliferative responsiveness to granulocyte-macrophage colony stimulating factor. AB - Tumor necrosis factor (TNF) is a protein produced by activated macrophages in response to endotoxin. The effect of recombinant murine TNF (rMuTNF) on the growth of murine tissue-derived macrophage colony-forming units (CFU-M) which are responsive to both macrophage and granulocyte-macrophage colony-stimulating factors (M-CSF and GM-CSF), was studied. TNF alone did not stimulate macrophage proliferation but did prolong their survival in vitro. The proliferative response of CFU-M to M-CSF, however, was greatly enhanced by the presence of TNF. The enhancement effect of TNF is dose-dependent, reaching a maximum at approximately 50 U/mL. In contrast, the proliferative responsiveness of CFU-M to GM-CSF was inhibited by the concurrent addition of rMuTNF. Both effects appear to be caused directly by rMuTNF, rather than by the secondary factor(s) produced by TNF treated macrophages. TNF treatment also induced a transient downmodulation of M CSF receptors in cultured macrophages and accelerated their uptake and use of exogenous M-CSF, which may account for, at least in part, the enhanced proliferative activity in response to M-CSF. Short-term treatment (24 hours) was not sufficient to induce either an enhancing or an inhibitory effect upon CFU-M. This study suggests an autoregulatory role for TNF in the production of mature tissue macrophages by selectively enhancing their proliferative response to lineage specific growth factor, M-CSF. PMID- 2183887 TI - Epidemiology of aplastic anemia in France: a prospective multicentric study. The French Cooperative Group for Epidemiological Study of Aplastic Anemia. AB - Incidence rates of aplastic anemia (AA) are rare among defined populations. Since June, 1984, a cooperative group, including 83 University medical centers throughout metropolitan France, prospectively recorded new cases of AA and followed them up. Inclusion criteria were: at least two depressed blood cell lineages (hemoglobin less than or equal to 10 g/100 mL and reticulocytes less than or equal to 50 x 10(9)/L, granulocytes less than or equal to 1.5 x 10(9)/L, platelets less than or equal to 100 x 10(9)/L) and a bone marrow biopsy compatible with the disease. Between May, 1984, and April, 1987, 292 cases were recorded. After exclusion of constitutional disease, 27 patients did not satisfy the inclusion criteria with relation to either bone marrow or blood evaluations and seven patients were initially misdiagnosed (shown in the follow-up), leaving 250 confirmed AA cases in the register. The annual incidence in France appeared to be about 1.5 per million inhabitants. The sex ratio of AA cases was similar to that of the population. In men, two peaks of incidence were observed: one between 15 and 30 years and one after 60 years. In women, the only peak was observed after 60 years. An excess of cases was observed in small towns but not in rural areas. About two of every three cases had severe AA, with a possible excess in younger cases. Based on a minimum follow-up of 1 year for 238 patients, the fatality rate was estimated at 17% at 3 months after diagnosis and at 34% at 1 year. Among 243 suspected etiologies reported by the physicians, 74% were declared idiopathic, 13% presumably associated to drug toxicity, and 5% related to hepatitis. AA appears to be a rare and severe disease in metropolitan France, often of unknown origin, a fact that emphasizes the necessity of controlled etiologic studies. PMID- 2183888 TI - The pattern of mutational involvement of RAS genes in human hematologic malignancies determined by DNA amplification and direct sequencing. AB - DNA from 161 patients with various forms of hematologic malignancies were investigated for mutations in exons 1 and 2 of the N-RAS, K-RAS and Ha-RAS gene by direct sequencing of DNA amplified in vitro by the polymerase chain reaction. Mutations involving either codons 11, 12, or 13 of the N-RAS gene were identified in 18 of the 161 patients. The relative frequencies of N-RAS gene mutations in these hematologic disorders was as follows: acute myelogenous leukemia (AML), 15%; acute lymphoblastic leukemia (ALL), 14%; myelodysplastic syndromes, 24%; and myeloid and lymphoid blast crisis of chronic myelogenous leukemia (CML), 3%. No correlation was observed between the presence of mutations and cytologic features or immunophenotype of these malignancies. Mutations involving codons 12 or 13 were equally prevalent, with a glycine to aspartic acid substitution being the most frequently encountered change. A single T-ALL case had a codon 11 mutation resulting in substitution of alanine with threonine. We failed to find mutations in exons 1 and 2 of the K-RAS or Ha-RAS genes in any case except a single AML with a mutation in codon 61 of the K-RAS gene. Also, no mutations were identified in chronic phase of CML, chronic lymphocytic leukemia. Ph1 positive ALL, non Hodgkin's lymphoma, Hodgkin's disease, or multiple myeloma. These results indicate that RAS mutations, especially those involving exon 1 of the N-RAS gene, are frequent only in a subset of hematologic malignancies. PMID- 2183889 TI - Increased nicotinamide adenine dinucleotide content and synthesis in Plasmodium falciparum-infected human erythrocytes. AB - Plasmodium falciparum-infected red blood cells (RBCs) are characterized by increases in the activity of glycolytic enzymes. Because nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP) are cofactors in the reactions of glycolysis and pentose phosphate shunt, we have examined NAD and NADP content in P. falciparum-infected RBCs. Although NADP content was not significantly altered, NAD content was increased approximately 10-fold in infected RBCs (66% parasitemia) compared with uninfected control RBCs. To determine the mechanism for the increase in NAD content, we examined the activity of several NAD biosynthetic enzymes. It is known that normal human RBCs make NAD exclusively from nicotinic acid and lack the capacity to make NAD from nicotinamide. We demonstrate that infected RBCs have readily detectable nicotinamide phosphoribosyltransferase (NPRT), the first enzyme in the NAD biosynthetic pathway that uses nicotinamide, and abundant nicotinamide deamidase, the enzyme that converts nicotinamide to nicotinic acid, thereby indicating that infected RBCs can make NAD from nicotinamide. In addition, infected RBCs have a threefold increase in nicotinic acid phosphoribosyltransferase (NAPRT), the first enzyme in the NAD biosynthetic pathway that uses nicotinic acid. Thus, the increase in NAD content in P falciparum-infected RBCs appears to be mediated by increases in NAD synthesis from both nicotinic acid and nicotinamide. PMID- 2183890 TI - Regulation of endogenous erythropoietin levels in anemia associated with myelodysplastic syndromes. PMID- 2183891 TI - Autocrine and paracrine growth regulation of breast cancer: clinical implications. AB - Research using experimental models of human breast cancer has broadened our understanding of the possible biochemical pathways regulating breast cancer growth. Breast cancer cells express receptors for and respond to a variety of steroid and polypeptide hormones and growth factors. Specific oncogenes are also expressed in breast cancer cells, and levels of expression may relate to tumor growth and aggressiveness. Recent studies have shown that breast cancer cells can even synthesize and secrete various growth factors that could stimulate tumor growth through autocrine and/or paracrine mechanisms. Secretion of some of these growth factors is regulated by estrogen, providing a possible mechanism for estrogen induced growth. Knowledge of these growth regulatory pathways has potentially important clinical implications. Blockade of these pathways offers new possible treatment strategies, much as antiestrogens have been used to inhibit tumor growth. Quantification of the expression of certain oncogenes, growth factor receptors, or the growth factors themselves, may provide prognostic information for the individual patient. Finally, it is plausible that measurement of these tumor products in body fluids might provide tumor markers that are useful in the diagnosis and treatment of breast cancer. PMID- 2183892 TI - Factors associated with obtaining nipple aspirate fluid: analysis of 1428 women and literature review. AB - Studies of cytologic and biochemical constituents of nipple aspirates of breast fluid have contributed to understanding the natural history of benign and malignant breast disease. We conducted multivariate analyses using 1428 women from a recent case-control study of breast disease to determine which factors were independently associated with the ability to obtain breast fluid from nonlactating women. We then compared results from these analyses to the results from five previous studies that also used the aspiration technique of Sartorius. Four factors were consistently associated across studies with increased ability to obtain breast fluid: 1) age up to 35 to 50 years; 2) earlier age at menarche; 3) non-Asian compared to Asian ethnicity; and 4) history of lactation. Exogenous estrogen use, endogenous estrogen concentrations, phase of menstrual cycle, family history of breast cancer, type of menopause, and less than full-term pregnancy consistently did not influence ability to obtain fluid. New findings from this study shed light on some apparently contradictory findings from the previous studies. In particular, this study showed that the effects of age on ability to obtain fluid appeared to be independent of the effects of menopause. Furthermore, discrepancies in previous findings on the effects of parity on ability to obtain fluid may be explained by our finding that the increased ability to obtain fluid from parous compared to nulliparous women applied only to parous women who had breastfed. PMID- 2183894 TI - Theories and simulation of protein folding. PMID- 2183893 TI - Victims of fraud: comparing victims of white collar and violent crime. AB - Mental health professionals have focused attention on the psychiatric sequelae of criminal victimization. This article compares the experience of white collar and violent crime victims on several parameters including statistical risk of victimization and psychiatric outcome after victimization. Emphasis is given to data obtained from interviewing 77 victims of a fraudulent financial scheme. PMID- 2183895 TI - Crystallographic determination of protein structure. PMID- 2183896 TI - The conformation of proteins and peptides in a membrane environment: an infrared spectroscopic approach. PMID- 2183897 TI - Application of laser-based fluorescence to study protein structure and dynamics. PMID- 2183898 TI - Experimental approaches to protein folding. PMID- 2183899 TI - Redesigning genes. PMID- 2183900 TI - Site-directed mutagenesis and its application to protein folding. PMID- 2183901 TI - The dissection and engineering of sites that affect the activity of an enzyme of unknown structure. PMID- 2183902 TI - BIREME: Latin American and Caribbean Health Sciences Information Center. AB - In the twenty years of its existence, BIREME has grown and evolved to meet the increasing information needs of health professionals in Latin America and the Caribbean. Recent emphasis has been on the adoption of new methods based on information technologies (including microcomputers, CD-ROMs, and advanced telecommunications) to improve and enhance services. Services discussed are bibliographic control, bibliographic searches, document delivery, selective dissemination of information (SDI), training, and publications. PMID- 2183903 TI - Continuing education needs of health care professionals. AB - Formal continuing education for health professionals continues to grow around the base of courses, conferences, and general reading. These formats serve the indispensable function of keeping health professionals abreast of the state of medicine. Since most formal continuing education activities are planned for groups, they cannot address the specific information needed in the care of individual patients. Furthermore, the knowledge gained is memory-based, and it is misguided to believe that facts learned in lectures will be remembered accurately enough for patient-care applications. A recent study has demonstrated that physicians often want additional knowledge when they are caring for patients and that access to knowledge is often difficult and time consuming. Advances in computer and telecommunications technology may ultimately permit immediate short answers to specific questions that arise during medical practice. It is time to expand the activities of the National Library of Medicine and the libraries within the Regional Medical Library (RML) network that provide valuable information for health professionals by developing methods to answer specific questions on the spot while health professionals are caring for patients. PMID- 2183904 TI - Physician information seeking: improving relevance through research. AB - Health sciences libraries have considerable potential as resources for both formal continuing professional education, as well as the informal continuing education that results from the professional's efforts to solve problems in daily practice. While there is a growing interest in making the resources of health sciences libraries more accessible to practitioners on a routine, day-to-day basis, there also needs to be more awareness of how, when, where, and why professionals look for information in the context of practical problems. This paper reviews recent research that identifies the context in which physicians seek information and advice from external sources, the information sources that physicians access, and the factors that influence which particular sources are sought. The results indicate that physicians vary in their information needs, preferences, motivations, and strategies for seeking information. This diversity suggests that health sciences libraries, in their efforts to be more accessible, should consider "market research" to determine the needs, preferences, and use patterns of the library's targeted users. Libraries may also benefit from exploring alternative methods of improving access to their resources. PMID- 2183905 TI - The role of paraprofessionals at the reference desk. PMID- 2183906 TI - The development of biomedical databases in the Soviet Union. PMID- 2183907 TI - David Bishop, 1928-1989. PMID- 2183908 TI - Experience with the free "inverted" groin flap in facial soft tissue contouring; a report on 6 flaps. AB - Reconstruction of the soft tissue facial contour defect in Romberg's disease and facial lipodystrophy using a free groin flap has been previously reported. However, controversy exists over the optimum placing of this flap within the cheek, i.e. whether it is better to have the dermis or subcutaneous fat side next to the muscle. Our experience with 6 flaps, 3 of which have been followed up for 3 1/2 years, is presented. In all cases the flaps were placed with the dermis side down, i.e. next to muscle. Although not a comparative study, our impression is that in the long term this technique reduces gravitational migration. Our experience with 2 flaps suggests that, in the early postoperative period at least, secure fixation by suturing to the muscle and periosteum is important. We believe that, in addition, this method gives a smoother contour and allows easy and safe secondary adjustments to be made where necessary. PMID- 2183909 TI - Congenital alveolar fusion. AB - Five cases are described of a condition in which the maxilla is fused to the mandible at birth, together with details of associated anomalies. A review of the literature provides a further nine single case reports that have appeared previously. An hypothesis of the possible embryological derivation of this condition is proposed. PMID- 2183910 TI - History of the development of the plastic surgery service in the Tayside region of Scotland, 1956-1986. PMID- 2183911 TI - Plastic surgery in Britain's Armed Services. PMID- 2183912 TI - Endothelin-1 inhibits platelet aggregation in vivo: a study with 111indium labelled platelets. AB - 1. A non-invasive technique for the scintigraphic determination of 111indium labelled platelet aggregation stimulated with submaximal doses of adenosine diphosphate (ADP, 56 micrograms kg-1 i.v.), collagen (100 micrograms kg-1 i.v.), platelet-activating factor (PAF, 0.1 microgram kg-1 i.v.) or thrombin (18 iu kg-1 i.v.) was used to investigate the platelet-inhibitory effects of endothelin 1 (ET 1) in anaesthetized rabbits in vivo. 2. ET-1 (1 nmol kg-1 i.v.) inhibited ADP stimulated platelet aggregation in vivo; a maximum inhibition of 78% of the control value was reached at 3 min, with 45% inhibition at 15 min, and a return to control values at 30 min after injection of the peptide. 3. ET-1 (1 nmol kg-1 i.v.) inhibited in vivo platelet aggregation in response to collagen or PAF by 86% and 52%, respectively, but had no effect on thrombin-induced platelet aggregation. 4. Indomethacin (5 mg kg-1 i.v.) abolished the ET-1-induced inhibition of ADP-stimulated platelet aggregation and significantly potentiated and prolonged the pressor response brought about by ET-1. 5. In conclusion, the data demonstrate that ET-1 potently inhibits platelet aggregation in the anaesthetized rabbit in vivo by releasing a hypotensive and anti-aggregatory cyclo-oxygenase product, presumably prostacyclin, into the circulation. PMID- 2183913 TI - A genetic study of idiopathic torsion dystonia in the United Kingdom. AB - The inheritance of idiopathic torsion dystonia (ITD) was investigated in 100 British families containing 107 index cases with generalized, multifocal or segmental dystonia, and 79 secondary cases. Fifty-eight index cases had affected relatives, usually in two or more generations. Nearly half of the secondary cases were asymptomatic. Paternal age was increased among the 49 single cases, parental consanguinity was not increased and there was no evidence of genetic heterogeneity. Eleven cases (10.3%) were Jewish, which exceeded the number expected, but they did not differ clinically or genetically from non-Jewish cases. The most likely explanation for the excess of Jewish cases is a founder effect in Eastern Europe. We conclude that, in the UK, approximately 85% of cases of ITD are due to an autosomal dominant gene with about 40% penetrance and highly variable expression, possibly reflecting environmental influences. Approximately 14% of these inherited cases may represent new mutations. The remaining 15% are probably nongenetic phenocopies, but are not clinically distinguishable. There was no evidence in this study for the existence of autosomal recessive or X linked forms of ITD. The estimated recurrence risk for first degree relatives of familial cases is 21%; the risk is lower for single cases. Of affected individuals, 75% will have developed symptoms or signs of dystonia by the age of 30 yrs. PMID- 2183914 TI - Plexiform neurofibroma: report of an unusual presentation. AB - We describe a plexiform neurofibroma discovered incidentally in a patient who was involved in a motor vehicle accident. The lesion simulated a subcapsular liver hematoma or diaphragmatic rupture on sonography, computed tomography and angiography. PMID- 2183915 TI - Malignant carcinoid within a recurrent sacrococcygeal teratoma in childhood. AB - Sacrococcygeal teratomas are uncommon tumors of childhood carrying a good prognosis if histologically benign and completely excised, especially if the coccyx is also excised. Carcinoids are also rare in children and only rarely associated with teratomas. We report the findings in a girl who had a malignant carcinoid within a recurrent malignant sacrococcygeal teratoma following its incomplete excision in the neonatal period. We believe that this is the first such case occurring in childhood. PMID- 2183916 TI - Sonography of hip joint in infective arthritis. AB - The most important determinant of outcome of a hip infection is the delay between the onset of the infection and treatment. Transient synovitis, and septic and tubercular arthritis of the hip remain common diagnostic problems. Conventional radiographic examinations are of little help in early diagnosis. Computed tomography, scintigraphy and magnetic resonance imaging, though informative, are expensive and not universally available. Ultrasonography (US) of the hip was done in 50 patients to define sonographic anatomy, detect joint effusions and correlate sonographic features with the etiology of the disease. Even small collections of fluid could be detected with accuracy. Both hypo- and hyperechoic synovial fluid was seen in septic arthritis, but hyperechoicity and a thickened capsule were the most characteristic findings. Synovial fluid had mixed echogenicity in tubercular and transient synovitis. The use of other (invasive) imaging modalities can be minimized because US can be used not only to demonstrate effusions early in the disease but also the status of the intra articular compartment, joint capsule, bony surface and adjacent soft tissues. Ultrasonography should be used more commonly to diagnose infective arthritis, and no patient should be subjected to arthrotomy or drainage if US has ruled out the presence of a fluid collection. PMID- 2183917 TI - Activity and energy expenditure. AB - The influence of small changes in activity on energy expenditure and hence on energy requirements and energy balance is assessed. Evidence from direct and indirect calorimetry suggests that differences in spontaneous minor activity could readily alter 24-h energy expenditure by as much as 20%. This compares with values in the order of 10% for moderate overfeeding and somewhat less than this during mild cold exposure. Individual variability in 24-h energy expenditure can therefore be accounted for not only by differences in resting metabolism and the thermic responses to energy intake and temperature but also by differences in minor activity. Interactions between activity and environmental factors such as nutrition and temperature can modify the effect of activity on energy balance. Very little is known about mechanisms that could account for differences in spontaneous activity and these need to be the subject of future investigations. PMID- 2183918 TI - Enhanced in vivo sensitivity of vanadyl-treated diabetic rats to insulin. AB - Vanadium has been reported to have insulin-like properties and has recently been demonstrated to be beneficial in the treatment of diabetic animals. In the present study, concentration dependence of the therapeutic effects of vanadium and the nature of interaction under in vivo conditions between vanadium and insulin were examined in streptozotocin-diabetic rats. During a 2-week period, blood glucose levels in all treated animals were decreased. At higher concentrations of vanadyl this decrease was greater and more rapid, and remained consistently lower for the entire treatment period. Daily intake of vanadyl, however, reached a similar steady state in all groups. Acute administration of submaximal doses of insulin, which had minimal effects in untreated diabetic rats, lowered blood glucose concentrations in vanadyl-treated and vanadyl withdrawn animals to control levels. Chronic treatment of streptozotocin-diabetic rats with submaximal levels of vanadyl and insulin, ineffective alone, also produced significant decreases in blood glucose levels when used in combination. Finally, the insulin dosage required to maintain a nonglycosuric state in spontaneously diabetic (BB) rats was reduced in the presence of vanadyl. These studies indicate that chronic oral vanadyl treatment (a) produces a concentration related lowering of blood glucose in diabetic rats, (b) potentiates the in vivo glucose lowering effects of acute and chronic administrations of insulin in streptozotocin-diabetic rats, and (c) substitutes for, or potentiates, the effects of chronic insulin therapy in spontaneously diabetic BB rats. PMID- 2183919 TI - Management of children with head trauma. Emergency Paediatrics Section, Canadian Paediatric Society. PMID- 2183920 TI - Periodic health examination, 1990 update: 1. Early detection of hyperthyroidism and hypothyroidism in adults and screening of newborns for congenital hypothyroidism. Canadian Task Force on the Periodic Health Examination. PMID- 2183922 TI - Progress in the treatment of early breast cancer. AB - Progress has been made in the prevention and early detection of breast cancer. As a consequence, there have been changes in treatment. Mammography, the standard screening procedure, is more widely accepted so that in situ and minimal lesions are diagnosed more often. There is a trend toward evaluation of local excision or observation as the treatment for noninvasive lesions. For invasive lesions, differences of opinion persist regarding the use of lumpectomy and irradiation versus modified radical mastectomy, but increasing data are helping to put the decisions on a sounder basis. Postoperative adjuvant therapy for patients with node negative lesions is still being evaluated. Up to the present time, these changes have not had an impact on mortality, but insufficient time has passed to evaluate the results of treatment of these very early lesions. PMID- 2183921 TI - The birth of birth control. PMID- 2183923 TI - Breast imaging. A critical aspect of breast conserving treatment. AB - Breast imaging provides essential information for the selection and management of patients with early breast cancer who are treated by lumpectomy, irradiation, or both. In addition to its role in the detection and localization of early breast cancer, imaging is also important in the postoperative evaluation and in the long term monitoring of these patients for the early detection of recurrence. The need for tailoring the examination at each stage and the significance of the findings for clinical and surgical management are discussed. PMID- 2183924 TI - Primary therapy for limited breast cancer. Surgical techniques. AB - Surgical techniques for breast cancer patients with early stages of disease are discussed. In situ cancers (LCIS, microscopic DCIS, and gross DCIS) present different risks and natural histories, and thus different treatment options are advised. For Stage I and earlier Stage II patients, either modified radical mastectomy or breast preservation with limited resection, axillary dissection, and subsequent breast irradiation are described. Immediate (or delayed) breast reconstruction offers other options for mastectomy patients. PMID- 2183925 TI - Adjuvant systemic therapy for patients with node-negative tumors. AB - Early adjuvant therapy studies, especially adjuvant chemotherapy studies, were performed almost exclusively on patients with histologically involved axillary lymph nodes ("node-positive" patients). These therapies were restricted to this group of patients because the toxicities of adjuvant therapy were believed too great to justify its use in patients with a very good prognosis until its benefits were fully established. However, after it was demonstrated that adjuvant therapy can significantly prolong the disease-free survival of almost all groups of node-positive patients and the overall survival of some patient subsets, adjuvant therapy trials specifically designed for patients without histologically involved lymph nodes ("node-negative" patients) were initiated. Results from some of the largest of these second generation trials were recently published, and the early results from these studies have generated new questions. For example, will the mature results from these studies be nearly identical to the results seen in node-positive patients, or will node-negative patients derive greater benefits from adjuvant therapy? Is it possible that adjuvant therapy will "cure" node negative patients but not node-positive patients? (Cure is defined here as an effect of therapy that returns a patient to the life expectancy she might have had if she had never been diagnosed with breast cancer). Is it possible that the added years of life from adjuvant therapy or that the number of node-negative patients who benefit are so small that these benefits will be outweighed by delayed toxicities that appear in patients who might have been cured even without adjuvant therapy? At present the available data to answer these questions definitely are either contradictory or nonexistent. PMID- 2183926 TI - Adjuvant therapy of stage II breast cancer. AB - Breast cancer is being diagnosed earlier with about 94% of patients presenting with disease limited to the breast or axilla. Despite this trend, more and more patients are receiving adjunctive therapy. In Stage II disease the results of clinical trials suggest that single agent chemotherapy has little if any role in adjuvant therapy. Polychemotherapy can improve survival in premenopausal women with a gain in outcome of about 26%. The duration of therapy appears optimal when given for 6 months. In postmenopausal estrogen receptor-negative women, chemotherapy also has a major role. Tamoxifen appears to offer approximately a 22% improvement in mortality for postmenopausal women. The longer duration of tamoxifen as adjuvant therapy appears to enhance the effect. Premenopausal women may also benefit using tamoxifen but the gain is less clear. Adding tamoxifen to chemotherapy does not enhance the effect. Patients with more than four positive lymph nodes may require more intensive therapy to show a major benefit. Radiotherapy can be integrated along with chemotherapy as adjunctive therapy. PMID- 2183927 TI - Primary therapy for limited breast cancer. Radiation therapy techniques. AB - Available data show that breast conserving surgery followed by radiation therapy results in freedom of breast cancer recurrence rates that range from 86% at 10 years to 80% at 20 years for Stage I and II carcinoma. Breast cancer recurrence may be reduced further by the administration of systemic chemotherapy. Mastectomy and breast conserving therapy give equal tumor control and survival, but the latter results in superior quality of life. To achieve the best tumor control with optimal cosmesis, certain generally accepted principles of surgical and radiotherapeutic management need to be followed. The surgeon must use a neat technique that avoids excessive removal of breast and axillary tissue, improper placement of the surgical scar in the breast, and the formation of seromas or hematomas, which result in breast or arm edema. The radiation oncologist must use supervoltage energy, fields that avoid excessive irradiation of the lungs and other sensitive structures, proper field matching, whole breast doses ranging from 4500 to 5000 cGy with fractions of 180 to 200 cGy per day, and brachytherapy or electron beam boost to achieve a total dose of approximately 6000 cGy in the tumor area. These principles should result in good to excellent cosmesis in more than 80% of treated breasts. Breast conserving management offers women an incentive to achieve early detection. Early detection is the most promising approach to reduce mortality from breast cancer. PMID- 2183928 TI - Tetra-amidines exhibiting anti-proteinase activity: effects on oriented migration and in vitro invasiveness of a Chinese hamster cell line transfected with the activated human T24-Ha-ras-1 oncogene. AB - In the present paper we have investigated the effects of aromatic tetra-amidines on attachment, oriented migration and in vitro invasiveness of the Chinese Hamster FH06T1-1 fibroblast lung cell line, transformed with the activated human T24-Ha-ras-1 oncogene. The FH06T1-1 cell line is tumorigenic in nude mice and displays growth properties and biological features clearly distinct from those of the FH06N1-1 cell line, obtained after transfection of the same fibroblast cells with the normal Ha-ras-1 proto-oncogene. Attachment, oriented migration and invasiveness were analysed by culturing the cells on a reconstituted extracellular matrix, composed of collagen IV, laminin, entactin and heparan sulphate proteoglycans. The results obtained demonstrate that oriented migration is performed only by FH06T1-1 cells and that tetra-benzamidines are effective inhibitors of oriented migration and "in vitro" invasiveness of these tumorigenic cells. These findings should encourage further studies on the possible antimetastatic effects of these antiproteinase tetra-benzamidines on experimental animals. PMID- 2183929 TI - Effects of progesterone on the response to epidermal growth factor and other growth factors in cultured human meningioma cells. AB - The presence of receptors for progesterone in a large proportion of human meningioma tissues is well established. The occurrence of increased rates of growth of meningiomas in situ during pregnancy suggests the existence of a relationship between high progesterone levels and the growth of meningiomas. However, experiments with cultured meningioma tissue (cells or explants) have shown only minimal effects of progesterone. It has been shown recently that many meningiomas have receptors for epidermal growth factor. In this paper we have investigated the response of cultured human meningioma cells to epidermal growth factor and other growth factors and the modulation of this response by progesterone and the progesterone-receptor blocking agent mifepristone (RU 38486). The results suggest that the presence of progesterone in the culture medium increases the sensitivity of meningioma cells to mitogenic stimuli, whereas mifepristone can counteract the stimulating effects of progesterone. PMID- 2183930 TI - Stimulation of tumor necrosis factor release from monocytic cells by the A375 human melanoma via granulocyte-macrophage colony-stimulating factor. AB - It has long been known that complex interactions occur between tumors and normal host immune cells. The human melanoma cell line A375 has been used previously as an indicator cell for tumor cell cytotoxicity mediated by monocytes. During other studies on this tumor cell line, we noted that the conditioned media harvested from A375 cultures induced both the human monocytoid cell line U937 and human blood monocytes to release the cytokine tumor necrosis factor (TNF). We characterized this tumor factor which induced TNF release by monocytic cells. Purification was performed using ammonium sulfate precipitation, ion exchange (DEAE) chromatography, gel filtration, and reversed-phase high performance liquid chromatography. The factor copurified with granulocyte-macrophage colony stimulating factor (GM-CSF). The purified material caused the release of TNF by U937 cells and stimulated formation of granulocyte-macrophage colonies in methyl cellulose. TNF release by U937 cells in response to A375-conditioned medium was inhibited by neutralizing antibodies to GM-CSF. The TNF-inducing activity in A375 conditioned medium was completely removed by an anti-GM-CSF affinity column. Western blotting using antibodies to GM-CSF confirmed a single Mr27,000 band in A375-conditioned medium. We found that recombinant human GM-CSF stimulated TNF production by the same cells as the tumor-conditioned medium. These data show that A375 human melanoma cells produce GM-CSF, which in turn causes TNF production by cells in the monocyte lineage. The combination of GM-CSF production by the tumor and TNF production by immune cells may influence not only tumor growth but also some of the paraneoplastic syndromes associated with malignancy such as hypercalcemia, cachexia and leukocytosis. PMID- 2183932 TI - c-Ha-ras oncogene expression in immortalized human keratinocytes (HaCaT) alters growth potential in vivo but lacks correlation with malignancy. AB - Spontaneously immortalized human skin keratinocytes (HaCaT) were transfected with the c-Ha-ras (EJ) oncogene via a plasmid construct which also contained the selectable neomycin gene. Clones were selected on the basis of G418 resistance. Those clones that had stable integrants of Ha-ras fell into 3 classes with respect to tumorigenicity. Class I clones were nontumorigenic, i.e., formed nodules which rapidly regressed. This phenotype is identical to that seen with parental HaCaT cells. Class II clones formed slowly growing, highly differentiated cystic or papillomatous-type benign tumors, and class III clones formed highly differentiated, locally invasive squamous cell carcinomas. The clones of all three classes exhibited similar morphology and growth potential in culture and retained the ability to reconstitute an epidermis-like stratified epithelium in transplantation experiments. Only the malignant clones showed locally invasive growth. Both the benign and the malignant clones exhibited higher levels of ras integration and variable levels of mutated p21 protein product. Thus, expression of the cellular Ha-ras oncogene in these human epithelial cells significantly altered growth regulation, resulting in varying degrees of growth potential in vivo, ranging from benign to malignant tumors. However, no direct correlation was seen between high levels of p21 expression and malignant growth. PMID- 2183931 TI - Bacterial lacZ gene as a highly sensitive marker to detect micrometastasis formation during tumor progression. AB - During tumor progression, micrometastases at their earliest stages have been difficult to analyze qualitatively or quantitatively because of a lack of suitably sensitive markers to discriminate small numbers of tumor cells from normal tissue cell populations. To overcome this problem, the Escherichia coli beta-galactosidase (lacZ) gene was introduced into human EJ Ha-ras oncogene transfected BALB/c 3T3 cells with subsequent injection of transfected cells into athymic nude mice. Using a chromogenic substrate (5-bromo-4-chloro-3-indoyl-beta D-galactopyranoside), the lacZ-bearing tumor cells at primary tumor sites as well as at secondary organs stain intensely blue and can be easily distinguished from the host tissue cells hours, days, or weeks postinjection. Staining of lacZ bearing tumor cells is specific and extremely sensitive in detecting micrometastatic foci in lungs and other organs, including brain and kidney for the first time. Stable integration of the lacZ and ras genes into cultured cells and subsequent tumor cells was verified by Southern blot analyses. The lacZ gene appears to be a stable marker during tumor progression in vivo based both on phenotypic (5-bromo-4-chloro-3-indoyl-beta-D-galactopyranoside staining) and on genotypic (Southern blot analysis) evidence. Furthermore, 5-bromo-4-chloro-3 indoyl-beta-D-galactopyranoside staining of tumor cells can also be used together with alkaline phosphatase staining relatively specific for endothelial cells to relate the topographies of metastatic cells and host blood vessels in embedded sections. By using the lacZ gene as a sensitive quantitative marker, analyses of micrometastasis development in the lung indicate that the ras oncogene contributes to the metastatic phenotype in this EJ Ha-ras model system, although further genetic and/or phenotypic alterations appear to be necessary for long term growth and development into overt metastases. These findings demonstrate the effectiveness and sensitivity of the bacterial lacZ gene as a phenotypic marker in tumor progression studies, providing both a qualitative and a quantitative tool in virtually any tumor system for examining micrometastasis formation in target organs and the relationship of tumor cells to host organ microenvironments. PMID- 2183933 TI - Convulsive disorders: mechanisms of epilepsy and anticonvulsant action. PMID- 2183934 TI - The role of the blood-brain barrier in movement disorders. AB - The entry of drugs and other biological compounds into the brain is a process that can be considered separately from the effects of those drugs and compounds once they have entered the brain. The rate of entry of compounds into the brain may occur either by passive diffusion or by carrier-mediated transport. Many processes interact to affect the amount of the compound that eventually enters the brain, including protein binding, systemic metabolism, and local metabolism and diffusion within the brain. PMID- 2183935 TI - Therapy of acute stroke. PMID- 2183936 TI - Functional state of the endothelium determines the response to endothelin in the coronary circulation. AB - STUDY OBJECTIVE - The aim was to study the effects of endothelin on the heart with special attention to an interaction with endothelium derived relaxing factor (EDRF). DESIGN - Bolus injections of various amounts of endothelin (1-300 ng) were given into the coronary circulation of isolated perfused rabbit hearts while coronary flow was held constant at 35 ml.min-1 and coronary perfusion pressure and other physiological variables were measured. The effects of indomethacin and haemoglobin on the responses were examined. EXPERIMENTAL MATERIAL - 15 New Zealand white rabbits, 1.0-1.5 kg, were used for the studies. The animals were anaesthetised and the hearts rapidly excised and perfused in the Langendorff manner. MEASUREMENTS and RESULTS - With coronary flow held constant, bolus injections of endothelin up to 300 ng caused no consistent increase in perfusion pressure, but resulted in a slight increase in left ventricular developed pressure. Indomethacin (10 microM) did not alter the response to endothelin; however, when endothelium dependent dilatation was inhibited by haemoglobin (10 microM), a dose dependent endothelin induced constriction was unmasked, with EC50 of 41 (SEM 15) ng, maximum +46(8) mm Hg. This constrictor response was further augmented by air infusion (0.5 ml), EC50 26(10) ng, maximum +102(12) mm Hg, and endothelin now caused a substantial dose dependent reduction in left ventricular contractile function. Endothelium dependent dilatation was not significantly reduced after air embolisation. CONCLUSIONS - The remarkable ability of the endothelium to protect against vasoconstrictor action of circulating endothelin in the coronary bed may not be due only to EDRF release, but perhaps also to an additional mechanism related to endothelial barrier of metabolic function. PMID- 2183937 TI - Insulin and beta adrenergic effects during endotoxin shock: in vivo myocardial interactions. AB - STUDY OBJECTIVE - Catecholamine concentrations are raised during endotoxin shock and may be responsible for myocardial insulin resistance in such a condition. The purpose of the investigation was to examine the effect of insulin on myocardial contractility and glucose uptake in the presence of beta adrenergic blockade during endotoxin shock. DESIGN - Endotoxin shock was obtained in dogs by giving S Typhimurium endotoxin intravenously (1 mg.kg-1) and the cardiac responses to insulin were determined under hyperinsulinaemic (4 U.min-1) euglycaemic clamp conditions during continuous beta adrenergic blockade (propranolol 150 micrograms.kg-1 + 5 micrograms.kg-1.min-1). SUBJECTS - 19 mongrel dogs of either sex, weight 20-25 kg, were studied under pentobarbitone anaesthesia. Seven dogs received endotoxin plus propranolol, and seven others received propranolol alone (control group). Five dogs received endotoxin but no propranolol or insulin. All other procedures were the same in each group. MEASUREMENTS and RESULTS - The exposed heart was prepared for coronary sinus blood sampling and measurements of circumflex artery blood flow (Q), instantaneous left ventricular pressure, and left ventricular wall thickness. Glucose uptake was calculated from product of Q and aortic-coronary sinus concentration difference. End systolic pressure dimension relationship was used to assess contractility. Myocardial performance was assessed from left ventricular dP/dtmax. Basal shock measurements were made 60 min post endotoxin. beta Adrenergic blockade did not interfere with insulin stimulated glucose uptake in controls, but was unable to restore the uptake response during endotoxin shock. Contractility was increased during endotoxin shock and this effect was abolished by beta adrenergic blockade. In controls the only variable affected by beta adrenergic blockade was left ventricular dP/dtmax (decreased). Insulin increased contractility during beta adrenergic blockade in controls but not in shock. Myocardial performance was depressed during shock. In controls, insulin increased myocardial performance; in shock this response was attenuated. CONCLUSIONS - The findings confirm that the myocardium becomes less responsive to the glucose uptake stimulating and positive inotropic effects of insulin during endotoxin shock. The data show that beta adrenergic activity is responsible for the increased contractile state of the heart during acute endotoxin shock, but is not the cause of the observed insulin resistant state. PMID- 2183938 TI - Effects of antihypertensive drugs on heart and resistance vessels. AB - STUDY OBJECTIVE - The aim of the study was to examine the effects of antihypertensive drugs on heart and resistance vessels to see whether regression of peripheral vascular hypertrophy accompanies reduction in cardiac mass. DESIGN Matched groups of spontaneously hypertensive and control rats were treated for 12 weeks with captopril (average dose 65 mg.kg-1.d-1) or hydrochlorothiazide (73 mg.kg-1.d-1) and compared to untreated groups. Perfusion pressure, which has been validated as an index of hypertrophy of resistance vessels, was determined in hind limbs of pithed rats at constant blood flow and maximum vasodilatation. SUBJECTS - Experimental animals were 14 week old male spontaneously hypertensive (SHR) rats (n = 41) and strictly age matched Wistar Kyoto rats (n = 12). SHR rats were assigned at random to three groups: (a) captopril treated (n = 15), (b) hydrochlorothiazide treated (n = 15), (c) control (n = 11). MEASUREMENTS and RESULTS - Mean perfusion pressure was 29.5(SEM 0.4) mm Hg in untreated Wistar Kyoto rats and 37.4(0.5) mm Hg in untreated SHR rats. In comparison with untreated SHR rats, treatment with captopril lowered blood pressure, perfusion pressure [35.2(0.3) v 37.4(0.5) mm Hg, p less than 0.01)], and left ventricular to body weight ratio [2.28(0.03) v 2.63(0.05) mg.g-1, p less than 0.01)]. Treatment with hydrochlorothiazide also lowered blood pressure but had no significant effect on left ventricular weight to body weight ratio [2.54(0.04)]. However, perfusion pressure was reduced to 35.3(0.5) mm Hg, p less than 0.01. CONCLUSIONS - For equal regression of vascular hypertrophy, captopril and hydrochlorothiazide had different effects on regression of left ventricular hypertrophy. Thus left ventricular and vascular structural changes may respond differently to the same drug in the same animal. PMID- 2183939 TI - Double-blind trial of pirenzepine versus sucralfate in the treatment of endoscopic duodenitis. AB - Thirty dyspeptic patients with endoscopic evidence of mild to moderate (nonerosive) duodenitis were randomly assigned to treatment with 50 mg of pirenzepine twice daily or 2 gm of sucralfate twice daily for four weeks. Posttreatment endoscopy revealed normalization of duodenal mucosa in half of the patients in each treatment group. The severity of dyspeptic symptoms was significantly reduced in both groups, with no significant between-group differences. PMID- 2183940 TI - Ceftazidime/metronidazole versus netilmicin/metronidazole in the treatment of perforated appendicitis in children. AB - One hundred children with peritonitis resulting from a perforated appendix were treated with ceftazidime or netilmicin. Metronidazole was added to both groups to treat the anaerobic organisms commonly associated with the infecting aerobic organisms in peritonitis. Escherichia coli was the most common aerobe found in peritoneal pus. Wound infection occurred in nine patients of the netilmicin group and in none treated with ceftazidime (P less than 0.01). No bacterial resistance was evident in the ceftazidime group, but gram-positive streptococci found in eight patients were resistant to netilmicin. Thus it is recommended that an antibiotic of the penicillin group be added if netilmicin is used to treat peritonitis. The results indicate that ceftazidime was more effective than netilmicin in the treatment of children with peritonitis resulting from a perforated appendix. PMID- 2183941 TI - Multicenter in vitro comparison of piperacillin and nine other antibacterials against 1,629 clinical isolates. AB - The antibacterial spectrum of activity of piperacillin was compared with that of other antibiotics against isolates of Escherichia coli, Enterobacter cloacae, Haemophilus influenzae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Pseudomonas cepacia, Pseudomonas maltophilia, Serratia marcescens, Enterococcus sp, Bacteroides fragilis, Bacteroides bivius, and Clostridium difficile obtained from laboratories at hospitals in St. Louis, in Memphis, and in Newark, New Jersey. Of the 1,629 isolates tested, 91% were susceptible to piperacillin, 90% to mezlocillin, 87% to ticarcillin/clavulanate and imipenem, 83% to ceftazidime, 81% to cefoperazone, 80% to ciprofloxacin, 77% to ceftriaxone, 71% to aztreonam, and 51% to cefoxitin. PMID- 2183942 TI - Radiation therapy of the para-aortic lymph nodes in carcinoma of the uterine cervix: the concurrent use of cimetidine to reduce acute and subacute side effects from radiation. AB - A prospective study of the effects of radiation therapy (RT) on para-aortic lymph nodes in uterine cervical cancer was conducted. As part of the study, cimetidine (800 mg daily) was administered during RT to relieve and prevent adverse reactions of the gastrointestinal tract caused by RT. In half of the patients, cimetidine (400 mg daily) was continued after RT was finished. The RT field was 7 to 8 cm wide and covered the area from the 4th lumbar to 11th thoracic vertebrae. The total dose administered was 45 Gy in 25 fractions over a five-week period. From September 1986 through October 1987, 89 patients were entered in this study. During RT, only slight gastrointestinal symptoms, such as nausea, vomiting, appetite loss, fatigue, and epigastralgia, were observed. These symptoms increased when cimetidine was withdrawn, but not in the patients who continued to receive cimetidine. It is concluded that cimetidine during and after RT can reduce the acute and subacute side effects of RT. PMID- 2183943 TI - 1,25 Dihydroxyvitamin D3-dependent inhibition of growth or killing of Mycobacterium avium complex in human macrophages is mediated by TNF and GM-CSF. AB - Vitamin D3 (D3) has been shown to activate several macrophage functions. To determine whether D3 could activate macrophages to kill or inhibit intracellular growth of Mycobacterium avium complex (MAC), human monocyte-derived macrophages were treated with D3 (10(-7), 10(-8), and 10(-9) M) 24 hr before or for 48 hr after MAC infection. All three concentrations were associated with inhibition of growth or killing of MAC in a dose-dependent fashion (28 +/- 4% and 22 +/- 3% of killing and inhibition of growth, respectively, at pharmacological concentrations) when added to the monolayer before injection or 60.4 +/- 6%, 50.4 +/- 3%, and 41.4 +/- 6%, respectively, when added to the monolayers after infection. We found that D3-treated macrophages produced increased concentrations of tumor necrosis factor (TNF) and granulocyte-monocyte colony stimulating factor (GM-CSF). Subsequently, macrophages were activated by D3 in the presence of anti TNF or anti-GM-CSF antibody: At 10(-9) M of D3 there was no inhibition of D3 dependent macrophage activation by anti-TNF antibody, whereas anti-GM-CSF antibody was associated with 100% inhibition. At 10(-8) M of D3, anti-TNF antibody inhibited 35 +/- 6% of killing, and anti-GM-CSF antibody was associated with 100% inhibition. At 10(-7) M of D3, anti-TNF antibody inhibited 58 +/- 4% and anti-GM-CSF antibody 89 +/- 3% of killing. D3 treatment is associated with anti-MAC activity in human macrophages, and this activity appears to be mediated by both TNF and GM-CSF. PMID- 2183944 TI - Synergism of interleukin 7 with the thymocyte growth factors interleukin 2, interleukin 6, and tumor necrosis factor alpha in the induction of thymocyte proliferation. AB - The role of previously defined thymocyte (Thm) growth factors in interleukin (IL) 7-induced Thm growth has not been fully elucidated. Therefore, experiments were designed to examine the capacity of IL-7 to: (i) directly induce Thm proliferation in the absence of experimental and known physiologic costimulators of Thm mitogenesis, and (ii) synergize with other Thm growth factors in supporting Thm proliferation. The data indicate that IL-7 is directly mitogenic for Thm; that is, IL-7 induces Thm proliferation in the absence of experimental comitogens such as concanavalin A, phytohemagglutinin, and phorbol myristate acetate and in the presence of neutralizing antibodies to murine IL-1 alpha, IL-1 beta, IL-2, IL-2 receptor (IL-2R)(p55), IL-2R(p70), IL-4, IL-6, and tumor necrosis factor (TNF). We also tested previously described Thm growth factors, i.e., IL-2, IL-4, IL-6, and TNF-alpha, for the capacity to synergize with IL-7 in Thm growth. Our results indicate that IL-2, IL-6, and TNF-alpha, but not IL-4, synergize with IL-7 in supporting Thm proliferation. These data suggest that IL-7 functions alone and in a synergistic fashion with other cytokines to regulate Thm growth. PMID- 2183945 TI - Closed head injuries in athletes. AB - Nervous system sports-related injuries constitute a major source of serious morbidity and mortality in athletes. In particular, acute closed head injuries account for some 6000 potentially preventable deaths and literally millions of episodes of less severe head injuries each year. The long-term significance of chronic head injuries resulting from repetitive blows to the brain is only now being fully appreciated. Similarly subtle neuropsychological changes are being increasingly recognized resulting from milder head injuries. Although head injuries are almost inevitable and unavoidable sequelae of most contact and competitive sports, much can and should be done to reduce the serious acute and chronic neurologic complications inherent in these activities. Prevention of catastrophic sports injuries by careful preseason examination, education, training, and conditioning, and ongoing counseling of the athlete is of paramount importance. The use of carefully fitted protective headgear, and avoidance of maneuvers that may directly result in serious head injuries are also key. The immediate evaluation, evacuation, and triage of the injured athlete must take place carefully and expeditiously. Skillful, experienced, and compassionate definitive care must then ensue. In the long term, the complications and analysis of accurate statistical data on the magnitude of sports injuries in general, and nervous system involvement in particular, must be studied. Presently, only a few sports have accumulated such data, such as in the National Football Head and Neck Injury Registry. In the final analysis, it is the cooperative responsibility of the medical and athletic communities to strive to reduce these tragic injuries. PMID- 2183946 TI - Cervical spinal stenosis with cord neurapraxia and transient quadriplegia. AB - The purpose of this article is to define as a distinct clinical entity, the syndrome of cervical spinal cord neurapraxia with transient quadriplegia. Sensory changes include burning pain, numbness, tingling, or loss of sensation, whereas motor changes consist of weakness or complete paralysis. The phenomenon of cervical spinal cord neurapraxia occurs in individuals with (1) developmental cervical spinal stenosis, (2) congenital fusions, (3) cervical instability, or (4) intervertebral disc protrusions when associated with a decrease in the anteroposterior diameter of the spinal canal. There is no evidence that the occurrence of cervical spinal cord neurapraxia predisposes an individual to permanent neurologic injury. However, patients with this syndrome and associated with cervical spine instability or acute or chronic degenerative changes should be precluded from further participation in contact sports. Those with developmental spinal stenosis or spinal stenosis associated with congenital abnormalities should be treated on an individual basis. PMID- 2183947 TI - Thoracic outlet syndrome. AB - Thoracic outlet syndrome remains a clinical diagnosis dependent almost exclusively on one's history and physical examination. Shoulder girdle depression, which may be present as a result of postural abnormalities or trauma (athletic or otherwise) has become recognized as an important cause of thoracic outlet compression. Management of this syndrome is entirely dependent on making an accurate diagnosis and defining the cause of neurovascular compression. Although thoracic outlet syndrome occurs infrequently, if the physician fails to consider this diagnosis, patients may suffer unnecessary and prolonged disability that may not only preclude optimal participation in athletics, but also interfere with certain activities of daily living. PMID- 2183948 TI - Brachial plexus injuries. AB - Brachial plexus injuries are not uncommon in sports. Knowledge of anatomy and neurophysiology is important to permit accurate diagnosis and institution of compressive treatment. Traumatic injuries can be caused by traction and compression. Unusual conditions such as acute brachial neuritis may also occur. Safe return to sports is permitted when strength party is achieved and rehabilitation is completed following neural recovery. PMID- 2183949 TI - Peripheral nerve injuries of the shoulder in the athlete. AB - Athletic injuries about the shoulder resulting in lesions of the suprascapular, axillary, long thoracic, musculocutaneous, and spinal accessory nerves are uncommon. Yet these lesions are well described in the literature, and they may occur as isolated injuries. Rarely do they occur following surgical procedures about the shoulder of the athlete. Furthermore, these injuries may mimic other more commonly occurring athletic injuries thus giving rise to diagnostic confusion. The clinical syndromes that result from these isolated lesions have been discussed, along with their mechanisms of injury. Increased awareness, careful physical examination, and EMGs may greatly simplify the diagnosis. The treatment and prognosis for these injuries has been outlined. PMID- 2183950 TI - Compressive neuropathies of the median and radial nerves at the elbow. AB - Compressive neuropathies of the median and radial nerves in the region of the elbow are a frequent cause of pain and weakness as well as sensory complaints. The problems associated with these neuropathies can be as severe and disabling as the more commonly encountered ulnar nerve neuropathies discussed elsewhere in this issue. Regardless of the nerve that is compressed, prompt recognition of the problem and the specific site of compression are important in order to institute effective treatment and limit, if not totally eliminate, permanent sequelae. Diagnosis and treatment are presented. PMID- 2183951 TI - Ulnar nerve problems in the athlete's elbow. AB - Ulnar neuritis at the elbow is a common entity affecting the athlete especially those involved in overhand sports. Inflammation of the ulnar nerve is a component of the disorders that affect the medial side of the elbow in athletics owing to the large tensile forces encountered. The treatment of the athlete with medial elbow pain should not be isolated to the findings of ulnar neuritis especially when attenuation of the ulnar collateral ligament is encountered. The prognosis of the athlete to return to their prior level of competition is related to their preoperative presentation. Patients with long-standing ulnar neuritis and severe lesions that include intrinsic muscle dysfunction and profound findings on EMG and nerve conduction studies have a less favorable outcome. The prognosis is also related to other associated conditions such as ulnar collateral ligament attenuation and degenerative arthritis. In athletes with symptoms primarily secondary to ulnar neuritis with minimal neurologic deficits and early treatment, the prognosis for return to competitive play is excellent. PMID- 2183952 TI - Vascular problems in the proximal upper extremity. AB - Vascular problems of the proximal upper extremity present with symptoms and signs of venous and arterial occlusion. They are rare, and sports medicine literature contains only case reports. Blunt trauma and activity requiring repetitive, overhead use of the arm are the usual mechanisms of injury. In athlete who perform repetitive upper-extremity activity, symptoms of easy fatigability of poorly localized pain and paresthesias should alert the treating physician to vascular occlusive disease. Published information suggests a good return-to-sport prognosis, but, because of the small number of cases, this information may be misleading. PMID- 2183953 TI - Neurovascular injuries in the wrists and hands of athletes. AB - Neurovascular syndromes in the wrist and hand are uncommon occurrences in the athlete. They are usually related to repetitive use of the wrist such as in racquet sports or sports with repetitive impact to the hands such as handball and catching. Common syndromes are discussed with regard to anatomy, pathophysiology, diagnosis, treatment, and return to sport. PMID- 2183954 TI - Vascular problems of the lower extremity in athletes. AB - The vascular anatomy of the lower extremity predisposes the popliteal area to traumatic injury owing to tethering at the adductor hiatus and the soleus arch. Knee dislocations should be followed with arteriography or exploration of the vessels. Epiphyseal separations of the proximal tibia and distal femur, as well as fractures about the knee, should be observed closely for 24 to 48 hours to ensure that the vascular status is intact. Traumatic pseudoaneurysms may arise from seemingly minor trauma and are treated surgically. The etiology of nonspecific claudication in the athletic population requires a careful history and physical examination and may require vascular studies in order to determine if the etiology is one of popliteal artery entrapment syndrome, adventitial cystic disease of the popliteal artery, or adductor canal outlet syndrome. Buerger's disease may be seen more frequently as the use of smokeless tobacco increases in the athletic population and may be distinguished from these other claudication-causing entities by its distribution to the upper and lower extremities in a distal fashion. A sense of alertness to these vascular entities will add to the quality of care of athletes. PMID- 2183955 TI - Compartment syndromes in athletes. AB - Compartment syndromes occur frequently in the leg in association with athletics, but may occur in the forearm and many other muscular compartments as well. Similar inciting events may result in either acute or chronic forms with vastly different clinical presentations. With an understanding of the anatomy and pathophysiology, and the ability to directly measure compartment pressures, an accurate diagnosis can be readily made. Acute forms require immediate fascial release to minimize muscle and nerve injury. Surgical treatment of the chronic form is highly successful and usually allows an early return to athletics. PMID- 2183956 TI - Neuropathies of the foot and ankle in athletes. AB - Although neuropathies in the athlete's foot and ankle are uncommon, they are often underdiagnosed. This is primarily due to the complex interplay of factors that are required for their presentation. The most frequently encountered entrapment syndromes (in decreasing order) involve the interdigital nerves, first branch of the lateral plantar nerve, isolated medial or lateral plantar nerves, posterior tibial nerve, deep peroneal nerve, superficial peroneal nerve, sural nerve, and saphenous nerve. A thorough knowledge of peripheral nerve anatomy is essential in establishing the diagnosis. Roentgenograms may reveal bony abnormalities that are the diagnosis. Roentgenograms may reveal bony abnormalities that are commonly contributory. Electrodiagnostic tests may be normal because these dynamic syndromes often resolve at rest. In most cases, correction of underlying etiologies combined with rest, NSAIDs, and occasionally injections will allow resolution of the syndrome. Recalcitrant cases may require surgical decompression, which frequently provides satisfactory results. PMID- 2183957 TI - Joint innervation in joint injury. AB - When considering joint innervation, it is important to appreciate that the joint receptors and the muscle tendon units about the joint interact in a complimentary manner forming a single afferent system. This system remains complex, and its overall function is still relatively unclear. Although the role of joint afferents can not be explicitly described, it is important to appreciate that alterations in joint innervation caused by athletic trauma can occur and can markedly affect joint function. PMID- 2183958 TI - Sodium intake modulates renal vascular reactivity to endothelin-1 in Dahl rats. AB - 1. The systemic and renal haemodynamic responses to endothelin-1 (ET1) were evaluated and compared to Angiotensin II (AII) in anaesthetized Dahl salt sensitive (DS) and salt-resistant (DR) rats on either low (0.1% NaCl in diet) or high (8% NaCl in diet) salt intake. 2. Baseline mean arterial pressure on low salt diet was similar in both strains, while on high salt diet it was 73 +/- 4 mmHg in DR rats and 119 +/- 8 mmHg in DS rats (P less than 0.05). Baseline renal blood flow (RBF) and renal vascular resistance (RVR) were similar in all groups. 3. AII in bolus injection induced a short, dose-dependent increase in blood pressure and renal vascular resistance and a fall in renal blood flow. The maximal pressure increase was significantly greater in DS rats on high salt diet than that in each of the other groups (P less than 0.05). The fall in renal blood flow and the increase in renal vascular resistance were attenuated in both strains on low salt diet. 4. ET1 induced an initial decrease followed by a prolonged increase in blood pressure; both phases were similar in all groups. However, renal vascular reactivity to ET1 was markedly modulated by salt intake. On low salt diet, following a bolus injection of ET1 (1 nmol/kg), RBF decreased by 34% in DR and by 20% in DS rats, while on high salt diet RBF decreased by 76% in DR and by 80% in DS rats (P less than 0.05 high vs low salt).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2183959 TI - Adhesion of frog pronephric tumor cells to normal cells cultivated on microcarrier beads. AB - The processes of cell adhesion and active spreading were assessed between frog normal pronephric, pronephric tumor and heterologous liver cells. Confluent monolayers were developed on collagen-coated microcarrier beads, then exposed to homologous or heterologous cells and cultivated with a rotary (orbital) flask culture technique at 23 degrees C. All three cell lines attach and actively spread on the collagen-coated microcarrier beads. Secondary attachment of normal (non-transformed) proliferating cells to their confluent monolayers occurs but cell spreading is restrained. Dissociated pronephric tumor cells adhere and actively spread on the surfaces of normal pronephric cells, and eventually encapsulate them. Normal pronephric cells do not adhere readily to the cell surfaces of pronephric tumor cells grown on microcarrier beads. Tumor cells also attach, actively spread and overgrow heterologous liver cells attached to microcarrier beads. Suboptimal temperatures (17 degrees C) slow tumor cell attachment and spreading on normal cells. Colder temperature (8 degrees C) permits tumor cell attachment and adhesion to normal cell-coated beads but active cell spreading is prohibited. The same temperature retards cell spreading directly on the collagen-coated beads. PMID- 2183960 TI - The effect of captopril on thallium 201 myocardial perfusion in systemic sclerosis. AB - In systemic sclerosis, abnormalities of myocardial perfusion are common and may be caused by a disturbance of the coronary microcirculation. We evaluated the long-term effect of captopril (75 to 150 mg per day) on thallium 201 myocardial perfusion in 12 normotensive patients with systemic sclerosis. Captopril significantly decreased the mean (+/- SD) number of segments with thallium 201 myocardial perfusion defects (6.5 +/- 1.9 at baseline and 4.4 +/- 2.7 after 1 year of treatment with captopril; p less than 0.02) and increased the mean global thallium score (9.6 +/- 1.7 at baseline and 11.4 +/- 2.1 after captopril; p less than 0.05). In a control group of eight normotensive patients with systemic sclerosis who did not receive captopril, no significant modification in thallium results occurred. Side effects with captopril included hypotension (six patients), taste disturbances (one patient), and skin rash (one patient). These side effects subsided when the dosage was reduced. These findings demonstrate that captopril improves thallium 201 myocardial perfusion in patients with systemic sclerosis and may therefore have a beneficial effect on scleroderma myocardial disease. PMID- 2183961 TI - Pill hoarding and hypercompliance. PMID- 2183962 TI - Components of high-level vision: a cognitive neuroscience analysis and accounts of neurological syndromes. AB - Neuroanatomical, neurophysiological, and computational constraints are used to motivate a set of hypotheses about the functional organization of high-level vision. A set of processing subsystems is posited that underlies the later stages of visual object recognition and identification; these subsystems have been implemented in a running computer simulation model. The model is damaged in a variety of ways, and its performance on a set of tasks is observed. Dysfunctions arise from disruptions of the subsystems, disruptions of their interconnections, compensations by intact subsystems, and diminished activational capacity. The most common dysfunctions of high-level vision following brain damage are then reviewed, and accounts are offered by reference to the stimulation model. According to the theory and model, each type of dysfunction can arise from numerous underlying causes, all of which are potentially distinguishable by empirical methods. PMID- 2183963 TI - Determination of near-optimum use of hospital diagnostic resources using the "GENES" genetic algorithm shell. AB - "GENES", a genetic algorithm shell developed by the authors, was used to optimize allocation of hospital resources for a small set of hypothetical patients. GENES creates a random population of rule sets of the IF..THEN type, which are variable in both the number of rules in each set and in the size of each rule. GENES applies each rule set to a patient data base, ranks the goodness of each set as applied, and uses the mechanisms of population genetics, i.e. mutation, crossover, inversion and survival of the fittest, to create a new, and often improved generation of rule sets. It also allows for the time dependent nature of medical tests, the possibility of injury associated with those tests, and the fact that results may not always be conclusive. Using 10-11 artificially created patients admitted under the diagnosis of possible gall bladder disease, a rule set was obtained which selected a testing strategy from a list of available hospital resources and correctly diagnosed all patients at minimum cost in no more than 3807 generations. PMID- 2183964 TI - Immunofluorescent characteristics of the diabetic cornea. AB - In view of the increasing awareness of corneal abnormalities in diabetes, five diabetic and five nondiabetic post-mortem corneas were investigated. Indirect fluorescent antibody techniques were used for the detection of immunoglobulin, complement components, fibrinogen, and fibronectin, as some of these had already been found in the kidney, pancreas, and skin of diabetic patients. There was no obvious difference in the deposition of IgG, IgA, IgM, fibrinogen, or fibronectin between diabetic and control corneal specimens. Five diabetic specimens versus three control specimens demonstrated positive staining at 1:50 dilution for complement components Clq, C3, and C4. This staining was primarily present in the epithelium. Of greater interest was the finding that complement components were present in the basement membrane of two diabetic patients, but were not found in nondiabetic patients. In conclusion, diabetic corneas demonstrate unusual staining for complement components in the epithelial basement membrane. PMID- 2183965 TI - Corneal myxoma. Case report and review of the literature. AB - Myxoma of the cornea is extremely rare. To our knowledge, only two cases have been reported in the literature. We report an additional case of a corneal myxomatous lesion that presented as a subepithelial, gelatinous, and whitish mass. Histologic examination revealed a loose mucoid stroma, rich in hyaluronic acid, with a relative paucity of cells. PMID- 2183966 TI - Impairment of renal function in medical intensive care: predictability of acute renal failure. AB - Acute causes and chronic risk factors for the development of acute renal failure were analyzed in prospective acquired data of 261 patients in a medical ICU. The population was divided into a group requiring dialysis treatment for established renal failure (n = 95) and a collective maintaining mild renal insufficiency (n = 166). Bivariate and linear discriminant analyses revealed that, above all, variables related to bacterial infections (sepsis and administration of antibiotic agents) and pancreatitis contributed to the discrimination, followed by bleeding, volume depletion, and chronic liver disease in the discriminant function. Bivariate analysis also yielded significant results for mechanical ventilation, CNS depression, and surgery. The importance of the nephrotoxic properties of aminoglycosides may be outweighed by their role as an indicator of severe infectious disease. The overall correct classification rate of the discriminant function was 78.5%, which reflects the importance of the predictor variables, but does not allow individual predictions. PMID- 2183967 TI - Determination of cardiac output during positive end-expiratory pressure- noninvasive electrical bioimpedance compared with standard thermodilution. AB - Many investigators have demonstrated the accuracy and reliability of thoracic electrical bioimpedance (TEB) in spontaneously breathing patients and under mechanical intermittent positive-pressure ventilation. Most of these studies showed a good correlation between TEB and invasive methods, such as thermodilution (TD) or the Fick method. But during PEEP, contrary results occur when comparing TEB and TD. In six patients undergoing neurosurgical interventions, TEB cardiac output measurements were compared during zero end expiratory pressure (ZEEP) and during PEEP at 8 cm H2O with a low respiratory rate. The data revealed a good correlation during ZEEP (r = .93) and during PEEP (r = .91). There was no significant statistical difference when measuring cardiac output by TEB during ventilation with PEEP. During normal or decreased cardiac output, TEB overestimated cardiac output compared with TD, whereas TEB underestimated cardiac output compared with TD during increased cardiac output, especially during PEEP. PMID- 2183968 TI - Optimal needle length of automatic injectors. PMID- 2183969 TI - Structure and function of suppressor tRNAs in higher eukaryotes. PMID- 2183970 TI - Enzymatic oxidation of xenobiotic chemicals. AB - Studies with biomimetic models can yield considerable insight into mechanisms of enzymatic catalysis. The discussion above indicates how such information has been important in the cases of flavoproteins, hemoproteins, and, to a lesser extent, the copper protein dopamine beta-hydroxylase. Some of the moieties that we generally accept as intermediates (i.e., high-valent iron oxygen complex in cytochrome P-450 reactions) would be extremely hard to characterize were it not for biomimetic models and more stable analogs such as peroxidase Compound I complexes. Although biomimetic models can be useful, we do need to keep them in perspective. It is possible to alter ligands and aspects of the environment in a way that may not reflect the active site of the protein. Eventually, the model work needs to be carried back to the proteins. We have seen that diagnostic substrates can be of considerable use in understanding enzymes and examples of elucidation of mechanisms through the use of rearrangements, mechanism-based inactivation, isotope labeling, kinetic isotope effects, and free energy relationships have been given. The point should be made that a myriad of approaches need to be applied to the study of each enzyme, for there is potential for misleading information if total reliance is placed on a single approach. The point also needs to be made that in the future we need information concerning the structures of the active sites of enzymes in order to fully understand them. Of the enzymes considered here, only a bacterial form of cytochrome P-450 (P-450cam) has been crystallized. The challenge to determine the three-dimensional structures of these enzymes, particularly the intrinsic membrane proteins, is formidable, yet our further understanding of the mechanisms of enzyme catalysis will remain elusive as long as we have to speak of putative specific residues, domains, and distances in anecdotal terms. The point should be made that there is actually some commonality among many of the catalytic mechanisms of oxidation, even among proteins with different structures and prosthetic groups. Thus, we see that cytochrome P-450 has some elements of a peroxidase and vice versa; indeed, the chemistry at the prosthetic group is probably very similar and the overall chemistry seems to be induced by the protein structure. The copper protein dopamine beta-hydroxylase appears to proceed with chemistry similar to that of the hemoprotein cytochrome P-450 and, although not so thoroughly studied, the non heme iron protein P. oleovarans omega-hydroxylase.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2183971 TI - Regular insulin. PMID- 2183972 TI - Multisystem failure in a child with HUS. AB - HUS is a complex multisystem disease. Research has increased our understanding of etiologic factors, presenting symptoms, lab findings, and course of the disease and has had an impact on treatment plans. As children present to community hospitals with symptomatology of dehydration, more careful analysis of electrolytes, BUN, creatinine, and hematologic smears have supported earlier diagnosis and directly impacted the morbidity and mortality of HUS. Astute ongoing nursing assessment and care in the critical care unit are crucial to promoting a favorable outcome. PMID- 2183973 TI - Rectal cancer: current management. PMID- 2183974 TI - Sensitivity and specificity of pathergy test results in Israeli patients with Behcet's disease. AB - Hyperreactivity of the skin to intracutaneous injection or needle prick (the pathergy test) is a unique feature of Behcet's disease. This phenomenon has been demonstrated to be highly sensitive and even specific in patients with Behcet's disease from Turkey, Japan, and Israel. A lack of positive reaction to this test has been reported in British and American patients. To evaluate the specificity of the pathergy test's results in Israeli patients with Behcet's disease, we compared their prevalence in these patients to that in a group of patients with other diseases associated with vasculitis. Forty-six Jewish and Arab Israeli patients with Behcet's disease, during a period of peak activity of their disease, and forty-six patients with other diseases associated with vasculitis, were studied for the hyperreactivity phenomenon. A positive reaction was observed in forty-five of forty-six patients with Behcet's disease, while the test gave negative results in all those with other diseases. Our study indicates, therefore, that the results of the pathergy test are highly sensitive and specific for Behcet's disease in Israeli patients. PMID- 2183975 TI - The evolving regulatory environment and bedside metabolic monitoring of the acute care patient. PMID- 2183976 TI - Current and future directions in the technology relating to bedside testing of critically ill patients. AB - Significant progress has been made recently in the measurement methods and instrumental approaches applicable to bedside testing of critically ill patients. While the "ideal" technology would involve the ability to obtain accurate stat profile values on a continuous basis via noninvasive methods, given the present state of noninvasive sensing technologies, this capability is unlikely to be achieved in the foreseeable future. In principle, invasive and on-line techniques offer more hope for future success in continuous bedside monitoring of all the key critical care analyses. However, success in these directions will come only when issues regarding sensor stability and sampling device/sensor biocompatibility are completely solved. Until then, it appears that the user friendly point of care type stat analyzers that can provide accurate values for all the key analytes, used in conjunction with existing noninvasive trend monitors (eg, pulse oximetry), will offer the most attractive approach for the effective treatment of critically ill patients. PMID- 2183977 TI - A comparison between electromyography and anal endosonography in mapping external anal sphincter defects. AB - Mapping of the external anal sphincter by anal endosonography was compared with the electromyographic findings in 15 patients with fecal incontinence after perineal trauma. Both examinations showed no defect in three patients. In the 12 patients with muscle defects, there was agreement on the quadrant involved in all patients. In seven patients, there was total agreement in the hours of the defect, in four there was a one hour discrepancy, and in one there was a two-hour difference in the measured defect. Correlation between the two techniques was high (r = 0.96; P less than 0.01). Anal endosonography is better tolerated by patients than electromyographic mapping and is a useful technique for assessing posttraumatic defects of the external anal sphincter. PMID- 2183978 TI - Progress in the assessment of lymphatic spread in rectal cancer. Rectal endoscopic lymphoscintigraphy. AB - Rectal endoscopic lymphoscintigraphy was performed in 10 control subjects and in a series of 85 patients with adenocarcinoma of the rectum as a prospective study to evaluate lymphatic drainage of the rectum and lymphatic spread in rectal cancer. Complete cranial drainage was demonstrated in all control subjects, and internal iliac nodes were also visible in 50 percent of cases. Results were correlated with histologic node examination in all patients operated upon for rectal cancer. Rectal endoscopic lymphoscintigraphy was assessed for sensitivity (85 percent), specificity (68 percent), overall accuracy (76 percent), positive predictive value (71 percent), and negative predictive value (83 percent). False negative and false-positive results are discussed. Rectal endoscopic lymphoscintigraphy represents the only method currently available for evaluation of lymphatic spread in rectal cancer. PMID- 2183979 TI - Aggressive surgical management of locally advanced primary and recurrent rectal cancer. Current status and future directions. AB - Patients with locally advanced primary and recurrent rectal cancer without gross evidence of extrapelvic cancer represent a complex challenge to the surgeon. In selected patients, radical incontinuity resection or resection combined with radical radiation therapy offers a high likelihood of local tumor control and, to a lesser degree, the possibility of cure. This article defines current approaches to the aggressive management of such patients and investigative strategies for the future. PMID- 2183980 TI - The examination of the heart: the importance of initial screening. AB - The screening examination of the heart and blood vessels require the use of the history, physical examination, electrocardiogram, and chest x-ray film. The relevant anatomy, pathology, and physiology responsible for the abnormalities found by using these methods of examination must be understood. The abnormalities that can be detected by the use of these methods of examination are discussed in this monograph. The techniques themselves are referred to as being low technology. The skill required in the use of these methods must be developed to its fullest. The data collected by using the history, physical examination, electrocardiogram, and chest x-ray film must be carefully analyzed in order for the examiner to diagnose the patient's cardiac problem. When possible, a complete cardiac diagnosis should be made according to guidelines formulated by the New York Heart Association. The four elements of a complete diagnosis are: Etiology, anatomy, physiology, and cardiac status and prognosis. In many cases, no additional data are needed and no additional data should be collected. When it is not possible to create a complete cardiac diagnosis from this information, the examiner must determine if it is wise and proper, given the patient's other health problems, to collect additional data that would permit a complete cardiac diagnosis. This effort hones the judgmental skill of the physician. When the cardiac diagnosis remains incomplete, or when a complete cardiac diagnosis is made but additional information is needed for follow-up purposes, carefully selected high technology should be used. With the unanswered questions in mind, the procedure used should be the one that answers the question with a predictive value that permits a defensible clinical decision. A complete medical problem list should be created for every patient. The cardiovascular problem must always be viewed in the context of other medical problems; there is no other way to make a sound judgment regarding the care of the patient with heart disease. When low technology, consisting of the history, physical examination, electrocardiogram, and chest x-ray film, is used poorly it is very likely that high technology will be used poorly. It is not possible to take a second step (high technology) without taking a well placed first step (low technology). PMID- 2183981 TI - Research on psychopathology and addiction: treatment implications. PMID- 2183982 TI - Some implications of animal alcohol self-administration studies for human alcohol problems. PMID- 2183983 TI - Research on drug use: a review of problems, needs and future perspectives. PMID- 2183984 TI - The social relevance of epidemiological research in drug use, abuse and dependence: a position paper. PMID- 2183985 TI - Research is badly needed to improve programmes for the prevention and treatment of drug abuse and drug dependence in Brazil. PMID- 2183986 TI - Impact of research on designing strategies for preventing and treating dependence on drugs: the case for developing countries especially African countries. PMID- 2183987 TI - Brief history of control, prevention and treatment of drug dependence in Japan. PMID- 2183988 TI - Historical studies and strategies against alcohol and drug abuse. PMID- 2183989 TI - The irrelevance of research to government policies on drugs. PMID- 2183990 TI - [Endosonographic diagnosis in gastroenterology]. PMID- 2183991 TI - [The value of blood pressure-lowering operations in portal hypertension]. PMID- 2183992 TI - [Clinical aspects and differential diagnosis of phobic cardiac neuroses]. PMID- 2183993 TI - [Cystic polyposis of the stomach]. AB - An X-ray contrast medium examination revealed extensive polyposis in the gastric fundus of a 66-year-old patient with intermittent heartburn. Physical examination and laboratory tests including carcinoembryonal antigen yielded no abnormal findings. Gastroduodenoscopy showed more than 100 polyps of about 5 mm diameter in the fundus and corpus of the stomach. Gastric mucosa was histologically intact. Numerous cysts lined by non-pathological epithelia were seen in the body and neck of the gastric glands. No polyps were found in the small bowel or colon. Since cystic polyposis does not tend to become malignant, no surgery was performed. Annual endoscopic controls, however, are recommended. PMID- 2183994 TI - [Bronchoalveolar lavage]. PMID- 2183995 TI - [The therapy of pleural empyema]. PMID- 2183996 TI - [Gene amplification by the polymerase chain reaction]. PMID- 2183997 TI - Drugs that alter blood viscosity. Their role in therapy. PMID- 2183999 TI - Estrogen therapy during menopause. Practical treatment recommendations. AB - The potential benefits of estrogen replacement therapy (ERT) for postmenopausal women are now generally recognised, and no scientist involved in this field of research will deny the gratifying results of hormone therapy. However, in the risk-benefit equation the adverse effects of ERT must be carefully considered. Most of the harmful adverse effects of ERT have been related firstly to the absence of progestational balance, and secondly to the fact that most of the estrogens previously available for clinical use were artificial and administered orally, resulting in intensive hepatic metabolism, leading to metabolic disturbances. The need for the addition of progestogen leads also to consideration of the adverse effects of these substances. During the past decade therapeutic improvements have been achieved. Knowledge about the different types of steroids now available, the right choice of dosage and duration of therapy according to the needs of the patient, and the new alternative delivery systems improves day by day. Various steroids are now available for clinical use. Among the estrogens, orally administered drugs, natural derivatives of estradiol, and nonoral drugs delivered by injection, implant, vaginal ring or cream, ointment or transdermal system are at the prescriber's disposal. Among the progestogens available to the prescriber and recommended to be added to ERT, the molecules derived from testosterone [norethisterone (norethindrone), norgestrel] are less prescribed than the molecules derived from progesterone (didrogesterone) or from 17-hydroxyprogesterone (medroxyprogesterone acetate). In menopausal therapy the latter derivatives from progesterone or 17-hydroxyprogesterone are preferable, but low doses of any type of progestogen could be both protective of the target organs and devoid of harmful effects. Careful consideration of contraindications of treatment and regular follow-up are prerequisites for safe therapy. Recent epidemiological data now demonstrate clearly that the use of ERT under these conditions affords protection against osteoporosis and cardiovascular disease. Clear benefits to women's health may therefore be obtained from the adequate choice and surveillance of therapy. PMID- 2183998 TI - Treatment of malaria--1990. AB - Malaria has become an increasingly common health problem in the 1970s and 1980s, both in areas where infection is endemic and in travellers returning to non endemic areas. The severity of infection varies widely, depending on the plasmodial species involved, and there is an extensive chemotherapeutic armamentarium currently available to combat malarial infection. Drug chemistry, pharmacokinetics, mechanism of drug action and resistance, and toxicities are outlined for the cinchona alkaloids (quinine and quinidine), chloroquine, amodiaquine, pyrimethamine, the sulphonamides, pyrimethamine/sulfadoxine, mefloquine, pyrimethamine/sulfadoxine/mefloquine, the sesquiterpene lactones, primaquine, and other drugs. A knowledge of the distribution of drug resistance is vital for the provision of effective antimalarial therapy, and current information in this area is outlined. Chloroquine remains the mainstay of treatment for the erythrocytic stages of Plasmodium vivax, P. ovale, P. malariae, and chloroquine-sensitive P. falciparum malaria. The dormant hepatic stages of P. vivax and P. ovale also require further treatment with primaquine. Quinine, alone or in combination with other drugs, is the primary agent used to treat chloroquine-resistant falciparum malaria. Falciparum infection can rapidly become fatal, therefore its complications of multiple organ failure, heavy parasitaemias, cerebral malaria, and hypoglycaemia must be recognised and managed promptly. Because these protozoal parasitic infections are now encountered throughout the world and can become life-threatening, a wide variety of practitioners must become more familiar with their correct treatment. PMID- 2184000 TI - Pruritus. Current concepts in pathogenesis and treatment. AB - Pruritus is an unpleasant sensation that provokes an urge to scratch. Many stimuli (notably histamine) are able to induce pruritus. The neural conduction of the itch sensation from the free unmyelinated nerve endings to the central nervous system mainly occurs on unmyelinated C fibres and the anterolateral spinothalamic tract. Pruritus is a common symptom in many skin or systemic diseases, but very little is known about the mechanism of the condition. Treatment evaluation is difficult; many methods do not evaluate the pruritus, but only the scratching, which is a consequence of pruritus. A number of asymptomatic treatments are only partially effective and we know little about their mechanism of action. Antihistamines remain the treatment of first choice for pruritus without known cause, but generally give incomplete relief. Whenever possible it is best to treat the underlying disease. PMID- 2184001 TI - Management of tuberculosis meningitis. AB - This article examines the detection, assessment, and therapeutic modalities available for tuberculosis meningitis. Without appropriate treatment this disease is fatal within 2 months of development, and mortality is closely associated with the stage of disease upon initiation of chemotherapy. Initial lumbar puncture reveals smear-positive acid-fast bacilli in up to 40% in most series; however, repeat examinations increase the yield, via direct smear, to as high as 87%. Analysis of cerebrospinal fluid is described, along with advanced techniques for early detection of this infection. Eight antituberculosis agents have known penetration into the cerebrospinal fluid. The most important prognostic factor is the neurological stage at which the individual presents at the initiation of therapy. Various chemotherapeutic approaches are available but it appears the use of rifampicin (rifampin) with isoniazid-containing regimens gives the best results. Regardless of the therapy undertaken, a significant number of individuals are left with some degree of neurological deficit. The roles of bacillus of Calmette and Guerin (BCG) vaccine, steroids, and neurosurgery in the treatment of this disease are also discussed. PMID- 2184002 TI - Dilevalol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in hypertension. AB - Dilevalol, the RR-stereoisomer of labetalol, is a non-cardioselective beta adrenoceptor antagonist with substantial partial beta 2-agonist and negligible alpha 1-blocking activity. Reduction in blood pressure during dilevalol administration is associated with peripheral vasodilatation, and heart rate remains essentially unchanged. Following oral administration, dilevalol is completely absorbed. Once-daily administration is possible, due to a long elimination half-life. Large well-controlled trials reveal that dilevalol is equivalent in antihypertensive efficacy to metoprolol, the ACE inhibitors captopril and enalapril, and the calcium antagonist nifedipine. Smaller noncomparative and comparative trials demonstrate the blood pressure-lowering effects of dilevalol and suggest an efficacy at least equivalent to that of the 'pure' beta-blockers atenolol and propranolol and the alpha 1-blockers urapidil and doxazosin. Dilevalol appears to be well tolerated, the most frequent adverse effects being dizziness, headache and diarrhoea in only about 7% of patients each. Unlike alpha 1-blockers and labetalol, dilevalol is not commonly associated with orthostatic hypotension. Thus, data suggest that dilevalol, with its distinctive pharmacological profile, is likely to be a useful addition to the options currently available for treating patients with mild to moderate essential hypertension. PMID- 2184004 TI - Chemotherapy for prostate cancer. Present concerns and future considerations. PMID- 2184003 TI - Amoxicillin/clavulanic acid. An update of its antibacterial activity, pharmacokinetic properties and therapeutic use. AB - Clavulanic acid enhances the antibacterial spectrum of amoxicillin by rendering most beta-lactamase-producing isolates susceptible to the drug. In clinical trials amoxicillin/clavulanic acid is clinically and bacteriologically superior to amoxicillin alone and at least as effective as numerous other comparative agents, such as orally administered cephalosporins, cotrimoxazole, doxycycline and bacampicillin, in the treatment of adults and children with the most common forms of infection encountered in general practice, i.e. urinary tract infections, upper and lower respiratory tract infections, otorhinolaryngological infections, and skin and soft tissue infections. It may also provide effective treatment for uncomplicated gonorrhoea, chancroid and gynaecological infections as well as acting as a prophylactic agent against surgical infection. Thus, in general practice environments where beta-lactamase production has restricted the effectiveness of amoxicillin, the combination of clavulanic acid with amoxicillin has clearly extended the usefulness of a tried and proven first-line antibacterial agent. PMID- 2184005 TI - Prevention of malaria. AB - With the increased spread of chloroquine-resistant Plasmodium falciparum malaria and mounting evidence of lack of efficacy and toxicity of alternative drugs, it has become extremely difficult to propose simple, widely applicable and uniformly acceptable recommendations for malaria chemoprophylaxis. With regard to specific drugs, it is clear that because of its toxicity amodiaquine should no longer be used for chemoprophylaxis, and that pyrimethamine/sulfadoxine should, for the most part, be used only as a presumptive therapy. The pyrimethamine/dapsone combination is promising, but data on its efficacy are limited. Although proguanil (chloroguanide) is recommended by several sources because of its safety, disturbing reports of chemoprophylaxis failure in Africa and a well documented lack of efficacy in South East Asia would suggest that its usefulness may be limited. However, a recent study has documented the efficacy of a proguanil-sulphonamide combination in Thailand, an area of high grade chloroquine resistance. Although long term studies of drug safety are not yet available, doxycycline and mefloquine appear to be the drugs of choice in areas where P. falciparum shows multidrug resistance. Regardless of the drug regimen recommended for chemoprophylaxis, travellers must be informed that no present-day antimalarial agent guarantees protection against malaria. PMID- 2184006 TI - Managing elevated blood lipid concentrations. Who, when and how? AB - Patients with elevated serum cholesterol concentrations, particularly men, should be treated to lessen their chance of subsequent morbidity from coronary heart disease. Reduction of elevated triglyceride levels is more contentious, but is justified in severely affected individuals. The levels requiring treatment can only be judged by consideration of the overall clinical setting, including patient age and sex, the presence of other risk factors and the particular lipoprotein abnormality. In general, relative youth, male sex, a low level of high density lipoprotein (HDL) cholesterol and a strong family history of coronary heart disease will favour vigorous therapy. The possibility that hyperlipoproteinaemia is secondary to some other metabolic disorder should be considered, particularly in regard to elevated triglyceride levels. PMID- 2184007 TI - New drug approaches to the treatment of heart failure in infants and children. AB - General considerations in planning therapy of heart failure include identification of the cause, rapidity of onset, and the age of the patient. Neonates and young infants with acute onset heart failure frequently develop acidaemia, respiratory compromise or failure, and metabolic derangements such as hypoglycaemia, hypocalcaemia or hypomagnesaemia. These complications require early recognition and urgent therapy. The diagnosis of heart failure in neonates with ductal dependent congenital cardiac lesions (such as coarctation of the aorta, hypoplastic left heart syndrome or pulmonary valve atresia) allows the early institution of alprostadil (prostaglandin E1) therapy to maintain patency of the ductus arteriosus, which stabilises these infants before surgical therapy. Classic therapy for infants with heart failure due to a large left-to-right shunt consists of salt restriction, diuretics and digoxin. If this treatment is inadequate an angiotensin converting enzyme (ACE) inhibitor (e.g. captopril) is added to therapy. The question then arises whether captopril and diuretics should be the initial therapy and digoxin added if this treatment fails. Acute heart failure may occur in the immediate postoperative period after cardiac surgery or may complicate acute overwhelming infections. Therapy consists of volume loading, vasodilator or inotropic agents. Heart failure due to various forms of chronic dilated cardiomyopathy usually responds to treatment with salt restriction, diuretics, digoxin and captopril. Acute deterioration requires treatment with vasodilators and/or inotropic agents. Heart failure in fetuses may occur from sustained supraventricular tachyarrhythmias, and may respond to treatment of the mother with antiarrhythmic agents such as digoxin or procainamide. PMID- 2184008 TI - Self-administration in the pharmacological treatment of impotence. AB - Recent innovative research into the physiology and pharmacology of erection and the introduction of intracavernous injection of vasoactive agents have revolutionised our approach to the diagnosis and treatment of impotence. A thorough understanding of the rationale, indications, precautions and potential complications of intracavernous self-injection is essential for successful management. The commonly used drugs for injection are papaverine, either alone or in combination with phentolamine, and alprostadil (prostaglandin E1). The major adverse effects include priapism, prolonged erection, and fibrosis of the erectile tissue. With the proper technique and appropriate dosage, this is a safe, minimally invasive, and highly effective treatment. PMID- 2184010 TI - Pergolide. A review of its pharmacological properties and therapeutic potential in Parkinson's disease. AB - When used to treat patients with Parkinson's disease pergolide acts at dopamine receptors in the corpus striatum to improve locomotor activity, reducing the tremor, gait disturbances, bradykinesia or akinesia and rigidity experienced by such patients. Treatment with pergolide often allows substantial reductions in concomitant levodopa dosage, and occasionally levodopa can be completely replaced by pergolide therapy in short term use. Pergolide has a long duration of action, thus reducing the wearing-off and end-of-dose phenomena frequently seen with long term levodopa therapy, suppressing fluctuations in levodopa response, and increasing total 'on' time. Despite a lack of well controlled studies comparing this drug with other dopamine agonist agents, pergolide appears to result in adverse effects and anti-Parkinson responses similar to those of bromocriptine and lisuride. Thus, pergolide would appear to be at least as useful as other dopamine agonists such as bromocriptine or lisuride for the management of patients with Parkinson's disease when administered in combination with levodopa. Future research should be directed towards establishing which patients are most likely to benefit from pergolide therapy, and clarifying the relative efficacy and safety of the anti-Parkinsonian drugs available to the clinician. If pergolide does provide clinical benefit when substituted for levodopa-adjunct drugs that are producing less than optimal control, this will be an advantage in a disease area which at present has few therapeutic options. PMID- 2184011 TI - [Arguments for cerebral dysfunction in obsessive-compulsive disorder. A review and synthesis of the literature]. AB - Until recently, particular interest was focalized on the association between Obsessive Compulsive Disorder (OCD) and biochemical markers, for testing the biological hypothesis. The neurotransmitter, most involved in OCD, seems actually to be serotonin. In contrast, few studies were concentrated on searching for the site of dysfunction in specific areas of the brain. Expanding exploration methods of the central nervous system (computerized EEG, evoked potentials, positions emission tomography...) and their recent application in OCD have given more evidence for the validity of the "neurodysfunctional" hypothesis and the localization of the dysfunction in OCD. PMID- 2184012 TI - [Lithium and converting enzyme inhibitors]. PMID- 2184009 TI - Etoposide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in combination chemotherapy of cancer. PMID- 2184013 TI - Effect of reduced luteinizing hormone concentrations on corpus luteum function during the menstrual cycle of rhesus monkeys. AB - To further define the relationship between plasma LH concentrations and progesterone secretion by the primate corpus luteum, we examined luteal function in rhesus monkeys in response to reduced LH concentrations during the luteal phase of the menstrual cycle. Five anovulatory rhesus monkeys received a pulsatile infusion of synthetic GnRH (6 micrograms/pulse; one pulse per h, iv) to restore menstrual cyclicity. During the early luteal phase (4-5 days after ovulation), the amount of GnRH administered per pulse was reduced to 1/250th or 1/750th of the standard GnRH infusion regimen. Plasma LH concentrations, determined by bioassay, were reduced by approximately 50% during cycles maintained by reduced GnRH concentrations compared with the standard GnRH dosage. Serum progesterone concentrations were maintained for 5-6 days after GnRH reduction and declined thereafter, and premature menstruations were observed in four of seven cycles maintained by the 1/250th GnRH reduction and four of six cycles maintained with the 1/750th GnRH reduction. These results are consistent with the hypothesis that luteal regression during the nonfertile menstrual cycles of primates is due primarily to an alteration in luteal cell responsiveness to LH, rather than a reduction in the gonadotropic drive to the corpus luteum per se. When plasma LH concentrations were reduced during the early luteal phase to values below those found during the onset of luteal regression in control cycles, luteal function was maintained for 5-6 days. However, as the luteal phase progressed, the reduced LH concentrations were unable to sustain progesterone secretion, and premature menses occurred in some, but not all, animals. PMID- 2184014 TI - Establishment of a series of pituitary clonal cell lines differing in morphology, hormone secretion, and response to estrogen. AB - Four kinds of cultured clonal cell line were established from estrogen-induced mammotropic pituitary tumor. These clones showed differences of hormone secretion, morphology, and response to estrogen. One clone tentatively designated MtT/E, consisted of spindle-shaped epithelial cells and showed the strongest adhesion to the culture dish, but did not secrete any pituitary hormone. The second cell line, designated MtT/S, secreted only GH, showed very weak contact with the culture dish, and proliferated almost anchorage independently. the MtT/S cells were mainly spherical and formed floating or weakly adherent clusters. Some of them had very long dendrite- or neurite-like cell processes. Electron microscopic examination of the MtT/S cells showed a normal somatotrope-like appearance, i.e. the presence in the cytoplasm of many GH-containing secretory granules, well developed rough endoplasmic reticulum, and Golgi apparatus. Furthermore, these cells secreted GH in response to stimulation with GRF. The third cell line with an ovoid cell appearance tentatively designated MtT/SM, secreted both PRL and GH, and showed anchorage-dependent proliferation. The fourth cell line designated MtT/Se secreted only a small amount of GH. Among these newly established cell lines, MtT/Se was the smallest in size and showed estrogen-dependent proliferation. The many small secretory-like granules present in the cytoplasm of MtT/Se cells showed no immunocytochemically positive reaction for anterior pituitary hormone. MtT/S and MtT/SM cell lines were also sensitive to estrogen. PMID- 2184015 TI - Antipeptide antibodies to two distinct regions of the androgen receptor localize the receptor protein to the nuclei of target cells in the rat and human prostate. AB - We have developed polyclonal antibodies to two synthetic peptides corresponding to the amino-(N-)terminal or carboxyl-(C-)terminal segments of the human androgen receptor (hAR) protein, as deduced from the nucleic acid sequence of the androgen receptor cDNA. Immunoreactive antisera were identified by solid phase enzyme linked immunosorbent assay and purified by peptide affinity chromatography. Specific immunoreactivity with the hAR was confirmed by immunoblotting, using both a fusion protein produced in E. coli that contains the C-terminal 880-amino acid sequence of hAR and the full-length receptor protein produced in COS cells after transfection with a plasmid containing the entire hAR-coding region. Immunohistological evaluation of rat and human prostatic tissue using anti-C terminal or anti-N-terminal antibodies demonstrated similar patterns of specific staining of the nuclei of epithelial and stromal cells. Castration resulted in a decrease in the amount of nuclear AR detected in the rat prostate after a short time of exposure to anti-C-terminal antibodies (less than 4 h), but did not alter the level of specific staining obtained with anti-N-terminal antibodies. This decrease in nuclear staining using anti-C-terminal antibodies could be reversed by treating castrated animals with dihydrotestosterone. When longer times of exposure to the primary antibodies were used, high levels of nuclear staining were obtained with both types of antibodies in prostate specimens from castrate as well as as intact rats. This immunohistochemical staining pattern contrasts with receptor measurements in rat prostate homogenates that indicate the partition of AR binding into the low salt (cytosolic) fraction in the castrate animal and into the high salt (nuclear) fraction in the intact animal. Our results suggest that the AR is predominantly a nuclear protein even in the absence of ligand and that dihydrotestosterone serves to tighten its association with the nucleus. These data also suggest that the immunoreactivity of anti-C terminal antibodies is influenced by the presence of dihydrotestosterone, presumably via an alteration in the physical state of the receptor protein. PMID- 2184016 TI - Glucose cycling is markedly enhanced in pancreatic islets of obese hyperglycemic mice. AB - Pancreatic islets from fed 7-month old lean and obese hyperglycemic mice (ob/ob) were incubated with 3H2O and 5.5 mM or 16.7 mM glucose. Incorporation of 3H into the medium glucose was taken as the measure of glucose-6-P hydrolysis to glucose. Glucose utilization was measured from the yield of 3H2O from [5-3H]glucose. Only 3-4% of the glucose phosphorylated was dephosphorylated by the lean mouse islets irrespective of the glucose concentration. In contrast, the ob/ob mouse islets at 5.5 mM glucose dephosphorylated 18% of the glucose phosphorylated and 30% at 16.7 mM. Thus, the islets of hyperglycemic mice demonstrate increased glucose cycling as compared to the islets of normoglycemic lean mice. PMID- 2184017 TI - The ontogeny of the rabbit brain glucose transporter. AB - We investigated the presence of three specific types of glucose transporters (GT) within the rabbit central nervous system during various developmental stages. Employing the Hep G2/brain-type insulin-insensitive and the insulin-responsive (IRGT; adipocyte/skeletal muscle type) GT antibody and cDNA, we studied protein and mRNA within the whole brain (25-, 27-, and 30-day-old fetus; 1-, 5-, 10-day old neonate; and adult), using cultured neuronal and glial cells, by Western and Northern blot analysis. Similarly, using the insulin-insensitive human fetal skeletal muscle-type (GLUT-3) GT cDNA, we characterized this mRNA by Northern blot analysis. Additional confirmation of cell specificity was sought by performing immunohistochemical staining on the neuronal and glial cells to detect the specific type of GT protein. We observed a developmental regulation of brain type GT within the whole brain, the peak abundance of protein and mRNA occurring in the adult, followed next by the fetus. No IRGT was detected within the whole brain at any stage of development. Contrary to the brain-type GT mRNA, GLUT-3 mRNA was found to be most abundant in the 10-day-old neonate and adult, followed next by the early neonate, with little in the fetus. Within isolated brain cell cultures, the mRNAs for the brain- and GLUT-3-types of GTs were abundantly present within glial cells, with considerably lesser amounts noted within the neurons. IRGT, on the other hand, revealed rather weak mRNA bands in both glial and neuronal cells. Western blotting revealed a brain type of GT protein within the glial cells alone; the neuronal cells for the most part were devoid of both the brain-type and the IRGT proteins. Further immunohistochemical staining confirmed the definite presence of the brain-type GT within the glial cells, with slight immunoreactivity observed within the neurons. Additionally, no significant IRGT immunoreactivity was observed within either cell type. We did not study the GLUT-3 type of immunoreactivity within neurons and glia. We conclude that both the Hep G2/brain and the GLUT-3 types, and not the IRGT, are developmentally regulated within the whole brain. Further, the Hep G2/brain and the GLUT-3 types of GTs are distinctly present within glial cells, with none to minute amounts present within the neurons. No IRGT protein is observed within the whole brain and the two cell types. These results suggest a differential expression of specific GT types within the neuronal and glial components of the brain. PMID- 2184018 TI - Corticosteroid 11 beta-dehydrogenase of rat tissues: immunological studies. AB - Monospecific polyclonal antibodies to purified homogeneous rat liver corticosteroid 11 beta-dehydrogenase were generated in rabbits. The antibodies were immunoprecipitins, but enzyme activity was not completely suppressed in the antigen-antibody complex. Two antibody preparations, 56-125 and 56-126, used to detect 11 beta-dehydrogenase antigen in Western blots, generated different staining patterns for kidney, liver, brain, and heart. Using the two antibodies together, the total number of antibody-reacting components in kidney was three, and that in liver was two. Based on rates of digestion with proteases, the two prominent immunoreactive proteins in kidney appeared to be structurally or conformationally different. A prominent immunostaining component was present in stomach. Tissues that showed immunochemical evidence of 11 beta-dehydrogenase antigen showed corresponding levels of 11 beta-dehydrogenase activity. Most active were liver, testis, kidney, and lung. Lower levels of activity were found in prostate and epididymis, brain, and reproductive tract. We conclude that 11 beta-dehydrogenase is widely distributed in rat organs and is present at low levels with significant exceptions. The data indicate that 11 beta-dehydrogenase may occur in several enzyme forms, and that the distribution of these forms is to some extent tissue specific. PMID- 2184019 TI - Rat spleen lymphocytes contain an immunoactive and bioactive luteinizing hormone releasing hormone. AB - An interaction between the immune and endocrine systems has been long known. This association is further strengthened by the finding that splenic lymphocytes have the capacity to produce molecules similar to if not the same as classical hormones, including several members of the opiate family, PRL, GH, and neuropeptide Y. Because of such findings and because of information from other laboratories suggesting that LHRH might have direct effects upon the immune system, we hypothesized that immune cells themselves might contain LHRH. Lymphocytes were purified from spleens of intact adult male Sprague-Dawley rats and the cells were lysed with sodium hydroxide. The concentration of immunoreactive LHRH was 403 +/- 184 pg/20 X 10(6) lymphocytes. Increasing amounts of lymphocyte lysate displaced [125-I]LHRH from LHRH antibody in a manner parallel to that produced by synthetic hypothalamic LHRH, suggesting immunologic similarity between lymphocyte and hypothalamic LHRH. Lymphocyte LHRH-like immunoactivity coeluted from Nova-Pak C18 columns with synthetic hypothalamic LHRH. When lymphocyte lysates were applied to rat anterior pituitary cells in monolayer culture, significant stimulation of LHRH secretion was seen, from 2,144 +/- 54 pg LH/ml.4 h to 15,364 +/- 587 pg LH/ml.4 h (P less than 0.001), a finding verified in five additional experiments. In other studies, this LH response evoked by lymphocyte lysates was found to be dose dependent and could be significantly inhibited by an LHRH-antagonist. Furthermore, when lymphocyte lysate and identically treated synthetic LHRH were HPLC fractionated, there was coelution of lysate and hypothalamic LHRH bioactivity. The lysate itself contained no substantial LH immunoreactivity. Thus, lymphocytes from spleens of adult male rats contain an immunoactive and bioactive LHRH, a finding further strengthening an association between the endocrine and immune systems. PMID- 2184020 TI - Insulin is a mitogen for isolated epiphyseal growth plate chondrocytes from the fetal lamb. AB - Insulin acts directly as a mitogen on isolated embryonic tissues but has been shown to be inactive at physiological concentrations on several fetal cell types. Since insulin availability is obligatory for optimal fetal growth, we have investigated its mitogenic actions on chondrocytes isolated from the epiphyseal growth plates of fetal lambs. Chondrocytes were isolated from the proximal tibial growth plate of lamb fetuses between 40 and 130 days gestation using collagenase and were cultured in monolayer before use between passages 2 and 6. The synthesis of DNA was assessed from the incorporation of [3H]thymidine after incubation in medium supplemented with glucose (0.7 mM-25 mM) with or without insulin (0.08 nM 167 nM). Increase in cell number was assessed after incubation with test medium for up to 8 days. Insulin substantially increased both DNA synthesis, and cell number, compared to control incubations with a biphasic dose response; an initial 3- to 5-fold increase in DNA synthesis occurring at approximately 1 nM insulin with a second response seen at approximately 50 nM. Within the physiological range of concentrations insulin was only 50% as active as insulin-like growth factor I (IGF I), but was 15 times more active than IGF II. Similar effects of insulin were observed throughout the fetal age range, although the DNA synthetic rate in basal medium declined with both fetal age and cell passage number. The mitogenic actions of insulin were glucose-dependent and were maximal in the presence of 2.7 mM glucose. Insulin did not cause any change in chondrocyte cell cycle duration. Chondrocytes released immunoreactive IGF II but no detectable IGF I. While exposure to insulin concentrations of approximately 50 nM or greater resulted in a statistically significant increase in IGF II release from chondrocytes, no change in IGF II release was seen in response to physiological insulin concentrations. However, exposure of cells to a blocking monoclonal antibody against human IGF I, McAb SM 1.2, which also negates the mitogenic actions of IGF II, consistently reduced insulin-stimulated DNA synthesis suggesting that IGF II presence may be necessary for optimal insulin action. Combination experiments using maximal concentrations of IGF I (13.3 nM) and increasing amounts of insulin (0.16 nM-1.67 nM) showed additive effects on DNA synthesis, suggesting that each hormone was acting through distinct receptor populations. We conclude that insulin, at physiological concentrations, may exert direct growth-promoting actions at the epiphyseal growth plates of the fetal lamb throughout gestation. PMID- 2184021 TI - Metabolic interfaces between growth and reproduction. III. Central mechanisms controlling pulsatile luteinizing hormone secretion in the nutritionally growth limited female lamb. AB - Growth retardation induced by dietary restriction in the lamb results in a low frequency of episodic LH secretion and, thus, delayed puberty. Such lambs respond normally to physiological doses of GnRH, indicating that the pituitary gland can function adequately during diet-induced hypogonadotropism. The current studies investigated central mechanisms underlying diet-induced hypogonadotropism. The first aim was to determine whether the hypothalamic GnRH secretory system is capable of normal function. The initial approach was to compare hypothalamic GnRH content between lambs on a restricted diet with low LH pulse frequency (less than 1 pulse/4 h; n = 5) and lambs on an ad libitum diet with high LH pulse frequency (4.5 +/- 0.4 pulses/4 h; n = 5). RIA of extracts of preoptic area and mediobasal hypothalamus/median eminence tissue blocks revealed no differences in GnRH content between lambs on a restricted diet and those on an ad libitum diet. The second approach was to determine if LH secretion could be induced by chemical stimulation of neuronal function with N-methyl-D,L-aspartate (NMA), an excitatory amino acid agonist. Initially, a single iv bolus of NMA was given to hypogonadotropic lambs on a restricted diet. There was a dose-dependent immediate rise in serum LH concentrations. All lambs responded to the highest dose (5.0 mg/kg BW; n = 6), and four of five lambs responded to the intermediate dose (1.0 mg/kg). No lambs responded to the lowest dose (0.2 ng/kg), despite a normal response to GnRH (2.5 ng/kg BW, iv). In a second experiment, hypogonadotropic lambs on a restricted diet were treated with repeated injections of NMA (5 mg/kg BW, iv) at either hourly intervals (n = 6) or every 3 h (n = 6). Each NMA injection induced a LH pulse in both treatment regimens over the entire 7-h experimental period. Thus, the nutritionally growth-limited lamb is capable of sustained production of LH pulses, which, we presume, reflect GnRH secretion. The second aim was to test the hypothesis that endogenous opioid mechanisms inhibit LH secretion during nutritionally induced hypogonadotropism, because opioid pathways are a poor inhibitory regulator of LH secretion in the normally developing sheep, even in the absence of ovarian steroids. We were unable to detect any effects of the opiate antagonist naloxone on LH secretion in the nutritionally growth-limited lamb. We conclude that central mechanisms controlling the release, rather than synthesis, of GnRH are limiting LH secretion when sexual maturation is delayed by growth retardation. Moreover, opioid inhibition is not the primary reason for hypogonadotropism during dietary restriction. PMID- 2184022 TI - Vanadate treatment of streptozotocin diabetic rats restores expression of the insulin-responsive glucose transporter in skeletal muscle. AB - Streptozotocin-treated rats were diabetic, as assessed by blood glucose and plasma insulin values, while vanadate treatment restored blood glucose values to normal. Immunoblot analysis using a monoclonal antibody to the insulin-responsive glucose transporter demonstrated a 70% decline in transporter expression in skeletal muscle of diabetic rats. Subsequent treatment of diabetic animals with vanadate resulted in renewed expression of the transporter to 87% of control levels. Northern blot analysis of total skeletal muscle RNA from diabetic animals revealed a 55% decline in the steady state level of muscle glucose transporter mRNA, while vanadate treatment led to a 187% increase in transporter mRNA over normal levels. These results support the conclusion that vanadate acts to relieve diabetic hyperglycemia by inducing expression of the insulin-responsive glucose transporter at the pretranslational level. PMID- 2184023 TI - Identification of committed mononuclear precursors for osteoclast-like cells formed in long term human marrow cultures. AB - Nonadherent marrow mononuclear cells enriched for hematopoietic progenitor cells were cultured in semisolid medium with recombinant human granulocyte-macrophage colony-stimulating factor for 9 days to form colony forming unit-granulocyte macrophage (CFU-GM) colonies. 1,25-Dihydroxyvitamin D was then gently layered over the cultures. After 2 weeks, approximately 30% of the colonies that formed were composed of cells with a unique polygonal morphology. One hundred percent of the polygonal cells in these colonies crossreacted with the monoclonal antibody 23c6, which preferentially recognizes osteoclasts. Homogenous populations of these polygonal cells formed multinucleated cells (MNC) in suspension culture, 100% of which cross-reacted with the 23c6 monoclonal antibody, and greater than 90% of the MNC contracted in response to calcitonin. Approximately 20% of these MNC formed resorption lacunae on calcified matrices. These results suggest that 1) early osteoclast precursors are derived from CFU-GM, the committed granulocyte macrophage progenitor; 2) committed mononuclear osteoclast precursors have a distinct polygonal morphology and cross-react with monoclonal antibodies that recognize mature osteoclasts; and 3) these mononuclear precursors are capable of forming multinucleated cells which fulfill the functional criteria for osteoclasts. PMID- 2184024 TI - Patterns of human chorionic gonadotropin expression in untreated and 8 bromoadenosine-treated JAR choriocarcinoma cells. AB - Although the biosynthesis and secretion of hCG by both normal and neoplastic trophoblasts have been documented, the regulation of these events is not well understood. We have used the JAR choriocarcinoma cell line to study the biosynthesis and secretion of this hormone. Using immunofluorescence, we have determined that less than 5% of cells expressed detectable hCG at a given time, and about 30% of hCG-producing cells were morphologically differentiated. Treatment of the cells with 8-bromoadenosine produced a 2- to 5-fold increase in hCG synthesis and secretion and increased the number of cells expressing hCG by 4 to 6-fold, without altering the percentage of morphologically differentiated cells expressing hCG. The effect on hCG biosynthesis was dose dependent and was induced maximally with a 24-h exposure to 8-bromoadenosine. However, exposure of JAR cells to 8-bromoadenosine for 2 to 6 h was sufficient to initiate a response. Treatment of JAR cells with the adenosine A2-receptor agonist N ethylcarboxamidoadenosine did not induce hCG biosynthesis. The effect of 8 bromoadenosine on hCG synthesis did, however, parallel the dose-effect curve for inhibition of thymidine incorporation and for decreased cell proliferation. We conclude that induction of hCG biosynthesis by 8-bromoadenosine occurs by inhibiting trophoblast cell proliferation, rather than by an adenosine receptor mediated event. The observed increase in hCG production may be due to induction of an intermediate differentiated cell type or an increase in the number of cells in an hCG-producing cell cycle phase. PMID- 2184025 TI - The use of mouse pituitary fragments to study LH secretion. AB - This work evaluated a perifusion system for studying LH secretion from the anterior pituitary (AP) of female mice. Pituitary fragments were challenged with LHRH, and the effluents assayed for LH. In general, the tissue exhibited augmented release to repeated stimulation. In the dose-response study, the amount of LHRH required to produce maximum and half maximum responses dropped almost 10 fold by the 3rd stimulus. In response to various pulse frequencies LH release increased with the frequency of the 100 nM LHRH dose, but the tissue became refractive to constant nonpulsatile stimulation. Other preparations, subjected to high-frequency 10 nM LHRH pulses, released LH in two distinct episodes. All but the first hour of the response was blocked by cycloheximide, confirming the role of protein synthesis in the sustained release of LH. By varying both the pulse frequency and amplitude, a LHRH protocol was found that produced a proestrous like surge. Lastly, rat and mouse tissues responded similarly to pulsatile LHRH, verifying their similar LH function during the preovulatory period. These studies demonstrate that the perifusion technique can be used for studying LH secretion in the mouse. Its application to other mouse-oriented studies is planned. PMID- 2184026 TI - Asbestos-induced release of a human alveolar macrophage-derived neutrophil chemotactic factor. AB - Neutrophils accumulate in the alveoli of asbestos-exposed individuals. In determining whether asbestos fibers induce the release of neutrophil chemotactic factor (NCF) from human alveolar macrophages, alveolar macrophages (10(6) cell/mL) obtained by bronchoalveolar lavage from six non-asbestos-exposed control subjects were exposed to crocidolite (0.1 and 1 mg/mL), chrysotile (1 mg/mL), or medium alone for 4 h, and NCF activity was measured in the supernatants in a 48 well microchemotaxis chamber with polycarbonate membrane filters (pore size, 3 microns) and purified human neutrophils. Alveolar macrophages in medium alone released negligible amounts of NCF (4 +/- 1 neutrophils per high-power field [N/HPF]). When macrophages were exposed to crocidolite (0.1 and 1 mg/mL), significant NCF release occurred (43 +/- 9 and 105 +/- 32 N/HPF, respectively; p less than 0.01 for each amount compare to alveolar macrophages cultured in medium alone). Chrysotile (1 mg/mL) induced similar NCF release (96 +/- 14 N/HPF; p less than 0.01 compared to unstimulated alveolar macrophages). Partial characterization of the NCF by Sephadex G-25 fine gel filtration demonstrated a molecular size of less than 1,000 daltons. These results show that human alveolar macrophages release NCF after exposure to asbestos. Release of NCF by alveolar macrophages in asbestos-exposed individuals may play a central role in the pathogenesis of asbestosis. PMID- 2184027 TI - Antagonism between intracerebroventricularly administered N-methyl-D-aspartate and bicuculline methiodide in induction of clonic seizures in mice. AB - N-Methyl-D-aspartate and bicuculline were administered alone or as a combination by intracerebroventricular injection to mice, and their convulsant activity was monitored. Both of these compounds elicited clonic seizures, though by different mechanisms. However, their simultaneous administration resulted in less than additive induction of clonic activity. PMID- 2184028 TI - Expression of potyviral polyproteins in transgenic plants reveals three proteolytic activities required for complete processing. AB - All proteins encoded by the plant potyvirus, tobacco etch virus (TEV), arise by proteolytic processing of a single polyprotein. Two virus-encoded proteinases (NIa and HC-Pro) that catalyze most of the proteolytic events have been characterized previously. The two proteins that are derived from the N-terminal 87 kd region of the viral polyprotein are a 35 kd protein and HC-Pro (52 kd). It is demonstrated in this study that a third proteolytic activity is required to process the junction between these proteins. Proteolysis at the HC-Pro N terminus to separate these proteins occurred poorly, if at all, after in vitro synthesis of a 97 kd polyprotein, whereas cleavage of the HC-Pro C terminus occurred efficiently by an autoprocessing mechanism. Synthesis of the same polyprotein in transgenic tobacco plants, however, resulted in complete and accurate proteolysis at both termini of HC-Pro. A point mutation affecting an amino acid residue essential for the proteolytic activity of HC-Pro had no effect on N-terminal processing. Expression in transgenic plants of a construct with a large deletion in the 35 kd protein coding region resulted in partial inhibition of HC-Pro N terminal cleavage, suggesting that the 35 kd protein may affect the proteolytic event but not in a catalytic role. We speculate that this cleavage event is catalyzed by either a cryptic potyviral proteinase that requires a host factor or subcellular environment for activation, or possibly a host proteinase. PMID- 2184029 TI - Protease secretion by Erwinia chrysanthemi: the specific secretion functions are analogous to those of Escherichia coli alpha-haemolysin. AB - A 5.5 kb DNA fragment carrying the functions necessary for the specific secretion of the extracellular metalloproteases B and C produced by the Gram-negative phytopathogenic bacterium Erwinia chrysanthemi has been sequenced. The fragment contains four transcribed and translated genes: inh, which codes for a protease inhibitor and is not required for protease secretion, and prtD, prtE and prtF, which share significant homology with the hlyB, hlyD and tolC genes required for alpha-haemolysin secretion in Escherichia coli. Mutations in any of the three prt genes abolish protease secretion. The prtD and prtE products (60 and 50 kd) contain at least one hydrophobic segment and the prtF gene product contains a signal sequence. PMID- 2184030 TI - The rhp6+ gene of Schizosaccharomyces pombe: a structural and functional homolog of the RAD6 gene from the distantly related yeast Saccharomyces cerevisiae. AB - The RAD6 gene of Saccharomyces cerevisiae encodes a ubiquitin conjugating enzyme and is required for DNA repair, DNA-damage-induced mutagenesis and sporulation. Here, we show that RAD6 and the rhp6+ gene from the distantly related yeast Schizosaccharomyces pombe share a high degree of structural and functional homology. The predominantly acidic carboxyl-terminal 21 amino acids present in the RAD6 protein are absent in the rhp6(+)-encoded protein; otherwise, the two proteins are very similar, with 77% identical residues. Like rad6, null mutations of the rhp6+ gene confer a defect in DNA repair, UV mutagenesis and sporulation, and the RAD6 and rhp6+ genes can functionally substitute for one another. These observations suggest that functional interactions between RAD6 (rhp6+) protein and other components of the DNA repair complex have been conserved among eukaryotes. PMID- 2184031 TI - ERCC2: cDNA cloning and molecular characterization of a human nucleotide excision repair gene with high homology to yeast RAD3. AB - Human ERCC2 genomic clones give efficient, stable correction of the nucleotide excision repair defect in UV5 Chinese hamster ovary cells. One clone having a breakpoint just 5' of classical promoter elements corrects only transiently, implicating further flanking sequences in stable gene expression. The nucleotide sequences of a cDNA clone and genomic flanking regions were determined. The ERCC2 translated amino acid sequence has 52% identity (73% homology) with the yeast nucleotide excision repair protein RAD3. RAD3 is essential for cell viability and encodes a protein that is a single-stranded DNA dependent ATPase and an ATP dependent helicase. The similarity of ERCC2 and RAD3 suggests a role for ERCC2 in both cell viability and DNA repair and provides the first insight into the biochemical function of a mammalian nucleotide excision repair gene. PMID- 2184032 TI - A major glycoprotein of the nuclear pore complex is a membrane-spanning polypeptide with a large lumenal domain and a small cytoplasmic tail. AB - One of a small number of polypeptides of the nuclear pore complex that have been identified is a major glycoprotein called gp210. Since it is very resistant to chemical extractions from membranes, gp210 was suggested to be integrated into nuclear membranes. In this study we have determined the membrane topology of this protein by biochemical and immunological approaches. We found that limited proteolysis of isolated nuclear envelopes with papain released a 200 kd water soluble fragment of gp210 containing concanavalin A-reactive carbohydrate. Immunogold electron microscopy with a monoclonal antibody showed that this domain is localized on the lumenal side of nuclear membranes at pore complexes. Anti peptide antibodies against two sequences near the C-terminus of gp210 were used to map possible membrane spanning and cytoplasmically disposed regions of this protein. From analysis of the protease sensitivity of these epitopes in sealed membrane vesicles, we determined that gp210 contains a small cytoplasmic tail and only a single membrane-spanning region. Thus, gp210 is a transmembrane protein with most of its mass, including the carbohydrate, located in the perinuclear space. This topology suggests that gp210 is involved primarily in structural organization of the pore complex, for which it may provide a membrane attachment site. PMID- 2184033 TI - HIV-1 replication is controlled at the level of T cell activation and proviral integration. AB - During progression of the Acquired Immune Deficiency Syndrome (AIDS), the human immunodeficiency virus type 1 (HIV-1) is harbored in CD4+ T cells, which act as the primary reservoir for the virus. In vitro, HIV-1 requires activated T cells for a productive infection; however, in vivo, the number of circulating T cells in the activated state that are potential targets for HIV-1 infection is low. We have investigated the ability of HIV-1 to infect resting T cells, and the consequences of such an infection. T cell activation was not required for HIV-1 infection; however, viral DNA was unable to integrate in resting T cells and was maintained extrachromosomally. Subsequent T cell activation allowed integration of extrachromosomal forms and led to a productive viral life cycle. Extrachromosomal forms of viral DNA were found to persist for several weeks after infection of resting T cells and, following T cell activation, these forms maintained their ability to integrate and act as a template for infectious virus. Several lines of evidence, including temporal analysis of HIV-1 replication and analysis of an HIV-1 integrase deletion mutant, indicated that extra-chromosomal HIV-1 DNA genomes were transcriptionally active. These results are compatible with a model whereby HIV-1 can persist in a non-productive extra-chromosomal state in resting T cells until subsequent antigen-induced or mitogen-induced T cell activation, virus integration and release. Thus agents that induce T cell activation may control the rate of HIV-1 replication and spread during AIDS progression. PMID- 2184034 TI - Initiation of translation at a UAG stop codon in the aldolase gene of Plasmodium falciparum. AB - The gene coding for the key glycolytic enzyme fructose-1,6-diphosphate aldolase of the human malaria parasite Plasmodium falciparum lacks a functional AUG initiation codon for translation. Protein sequences of natural or in vitro translated aldolase include the candidate start methionine residue at internal positions. No additional AUG start codon is found in genomic DNA, cDNA or mRNA sequences. Instead, a UAG chain termination codon is recognized as the start signal of protein synthesis in vivo and in vitro. PMID- 2184035 TI - Selenomethionyl proteins produced for analysis by multiwavelength anomalous diffraction (MAD): a vehicle for direct determination of three-dimensional structure. AB - An expression system has been established for the incorporation of selenomethionine into recombinant proteins produced from plasmids in Escherichia coli. Replacement of methionine by selenomethionine is demonstrated at the level of 100% for both T4 and E. coli thioredoxins. The natural recombinant proteins and the selenomethionyl variants of both thioredoxins crystallize isomorphously. Anomalous scattering factors were deduced from synchrotron X-ray absorption measurements of crystals of the selenomethionyl proteins. Taken with reference to experience in the structural analysis of selenobiotinyl streptavidin by the method of multiwavelength anomalous diffraction (MAD), these data indicate that recombinant selenomethionyl proteins analyzed by MAD phasing offer a rather general means for the elucidation of atomic structures. PMID- 2184036 TI - Human autoantibodies identify a nuclear chromatin-associated antigen (PSL or p55) in human platelets. PMID- 2184037 TI - Capping of Con A receptors and actin distribution are influenced by disruption of microtubules in Dictyostelium discoideum. AB - Capping of Concanavalin A (Con A) receptors can be inhibited in Dictyostelium by treatment of amoebae with the microtubular drug tubulozole. In cells that were incubated with Con A or with fluorescent Con A conjugate the capping process was completed in 30 min as could be demonstrated by fluorescence microscopy and Con A peroxidase labeling. In the presence of 10(-5) M tubulozole redistribution of the receptors did not proceed beyond a stage that can be characterized as patching. The effect of the drug on microtubule integrity was checked by electron microscopy and immunofluorescence of tubulin. Treatment resulted in shortening of the peripheral parts of the microtubules, in agreement with results described by other authors. Electron microscopy confirmed that the Con A receptor complexes remained on the plasma membrane and were not internalized. The distribution of F actin in Con A-treated cells showed a pattern closely resembling that of Con A. Cells that were also treated with tubulozole remained spherical and did not resume significant directional movement until tubulozole was removed from the medium. It is concluded that microtubules are involved in the rearrangement of the microfilament network in moving cells. PMID- 2184038 TI - Pancreatic acinar cells in culture: expression of acinar and ductal antigens in a growth-related manner. AB - In the current study two monoclonal antibodies (mAb) were used to investigate the expression of adult acinar and duct cell-specific antigens and their relationship with cell growth in primary acinar cell cultures. We have previously found that adult mouse pancreatic acinar cells divide in primary culture. Furthermore, during growth the cells lose their differentiated morphology and exhibit decreased expression of secretory proteins, followed by some degree of morphological redifferentiation after reaching confluency. A mAb specific in the adult pancreas for acinar cells (mAb Acinar-1) and another specific in the adult pancreas for duct cells (mAb Duct-1) were generated using such cultures as the immunogen. The starting material for the cultures consisted of predominantly Acinar-1 positive cells which incorporated [3H]thymidine, as determined by autoradiography and immunofluorescence labeling. However, expression of the acinar antigen persisted for only the first 3 to 7 days in culture. By contrast, expression of the duct antigen was rare until after 5 days in culture and was highest at day 9, the peak of cell growth. Dual label immunofluorescence showed that during the growth phase fewer cells expressed the acinar antigen, most expressed the duct antigen, and occasional cells expressed both antigens. After reaching confluency, the growth rate declined from days 15 to 21, and the cells progressively regained the acinar antigen with a concomitant loss of the duct antigen. mAb labeling was morphometrically quantitated and showed that more than 97% of the labeled area was Acinar-1 positive at 3 days, which decreased to approximately 16% at day 9, and then returned to over 97% by day 21 of culture. Ultrastructural immunolabeling showed that Acinar-1 positive cells at 21 days had well organized rough endoplasmic reticulum and small apical vesicles, while Duct 1 positive cells were undifferentiated in appearance (day 9) or had numerous mitochondria (day 21). Thus, changes in cell-specific antigens were paralleled by cell type associated morphological characteristics and indicate that adult acinar cells can retrodifferentiate to a more duct-like cell while retaining the potential to express an acinar-specific antigen. PMID- 2184039 TI - Distribution of peroxisomes and glycolate metabolism in relation to calcium oxalate formation in Lemna minor L. AB - Calcium oxalate formation in Lemna minor L. occurs in structurally specialized cells called crystal idioblasts. Cytochemical and immunocytochemical protocols were employed to study the distribution of peroxisomes and the enzymes glycolate oxidase, glycine decarboxylase and ribulose 1,5-bisphosphate carboxylase oxygenase (RuBisCO) in relation to synthesis of oxalate used for Ca oxalate formation. These enzymes are necessary for photorespiratory glycolate synthesis and metabolism. Using catalase cytochemistry, microbodies were found to exist in crystal idioblasts but were smaller and fewer than those found in mesophyll cells. Glycolate oxidase, which can oxidize glycolate to oxalate via glyoxylate, could not be found in microbodies of crystal idioblasts at any stage of development. This enzyme increased in amount in microbodies of mesophyll cells as they matured and could even be found in dense amorphous inclusions of mature cell peroxisomes. Glycine decarboxylase and RuBisCO could also be detected in increasing amount in mesophyll cells as they matured but could not be detected in idioblasts or were just detectable. Thus, Lemna idioblasts lack the machinery for synthesis of oxalate from glycolate. Based on these results and other available information, two general models for the generation and accumulation of oxalate used for Ca oxalate formation in crystal idioblasts are proposed. The biochemical specialization of crystal idioblasts indicated by this study is also discussed with respect to differentiation of cellular structure and function. PMID- 2184040 TI - Acute haemodynamic and neurohumoral effects of intravenous nisoldipine in patients with severe congestive heart failure. AB - Twenty patients (5 females, 15 males) with severe heart failure (NYHA IV), due to coronary artery disease in 14, and congestive cardiomyopathy in 6, received an intravenous bolus of the calcium blocker nisoldipine 0.2 mg followed by a continuous infusion of 0.2 micrograms.kg-1.min-1. Haemodynamic measurements were performed at baseline and after 30 min. The mean arterial pressure fell from 91 to 73 mmHg, pulmonary capillary wedge pressure from 31 to 26 mm Hg and systemic vascular resistance from 1695 to 1040 dyn.s.cm-5. The cardiac index (2.2 to 2.71.min-1.m-2, and stroke volume index (25 to 33 ml.m-2) were markedly increased. There was no reflex tachycardia as the heart rate dropped from 92 to 85 beats.min-1. Plasma renin activity and norepinephrine concentration did not change significantly. The findings indicate that nisoldipine acts as a strong vasodilator and that it has a beneficial acute haemodynamic effect in patients with severe left heart failure irrespective of its aetiology. PMID- 2184041 TI - Review of methods and criteria for the evaluation of bioequivalence studies. AB - Guidelines for the performance and analysis of bioequivalence studies are not very specific. The advantages and disadvantages of the following methods and tests are discussed: analysis of variance by summation or by use of general linear models, nonparametric procedures, aposteriori probabilities and tests on the normality of residuals and on the variability of the results. Arguments for or against an analysis of data after logarithmic transformation versus analysis of untransformed data are presented. If the confidence intervals lie within certain limits, preparations may be considered equivalent. The criteria leading to those limits are discussed. It is recommended that concentration-dependent data of bioequivalence studies be evaluated by analysis of variance after logarithmic transformation, applying general linear models. Data that by theoretical reasons cannot be normally or log-normally distributed should be analysed by nonparametric methods. Otherwise these methods can only be recommended if a significant deviation from normality has been noted and only for two-way cross-over designs. For a geometric evaluation (after logarithmic transformation) the regions of acceptance should be symmetrical in the logarithm, e.g. (80%, 125%). PMID- 2184042 TI - The effect of chronic clozapine and haloperidol on basal dopamine release and metabolism in rat striatum and nucleus accumbens studied by in vivo microdialysis. AB - The effects of chronic treatment with clozapine and haloperidol on basal dopamine release and metabolism were studied in the striatum and the nucleus accumbens of awake, freely moving rats using in vivo microdialysis. Chronic haloperidol (2 mg/kg X 21 days) but not chronic clozapine (20 mg/kg X 21 days) decreased basal dopamine release and metabolism in both the striatum and the nucleus accumbens. These results differ significantly from those previously reported with in vivo voltammetry. Possible explanations are discussed. PMID- 2184043 TI - The role of multiple dopamine receptors in apomorphine and N-n propylnorapomorphine-induced climbing and hypothermia. AB - Apomorphine and N-n-propylnorapomorphine (NPA) were compared for their ability to induce stereotyped cage climbing and hypothermia in mice. Climbing behavior was produced by similar doses of apomorphine and NPA (0.625-2.5 mg/kg s.c.), whereas NPA was 43 times more potent than apomorphine in inducing a hypothermic response. SKF38393 caused a shift to the left in the dose-response curve for NPA-induced climbing, the ED50 changing from 0.98 to 0.014 mg/kg. SKF38393 had no effect on apomorphine-induced climbing behaviour. The climbing response produced by apomorphine was antagonised by both D-1 and D-2 antagonists. Climbing behaviour induced by NPA (2.5 mg/kg) could be antagonised by SCH23390 but not by clebopride, however climbing behaviour induced by a low dose of NPA (0.06 mg/kg) plus SKF38393 could be blocked by both D-1 and D-2 receptor antagonists. The hypothermic responses produced by either apomorphine or NPA could only be reversed by the selective D-2 antagonist, clebopride. These results demonstrate that dopamine agonist-induced stereotyped cage climbing requires both D-1 and D-2 receptor stimulation, whereas the hypothermic response is D-2-mediated. The results also show that it is possible to assess the relative activity of a dopamine agonist at D-1 or D-2 receptors in vivo by comparing the ability of the compound to induce hypothermia and climbing behaviour. PMID- 2184044 TI - Changes in proteinase activities during the differentiation of murine erythroleukemia cells. AB - Changes in intracellular proteinase activities were examined during DMSO-induced differentiation of murine erythroleukemia cells. Suc-APA-MCA hydrolytic activity was significantly decreased, and apparent ATP-dependent multicatalytic proteinase activity was also decreased with MEL cell differentiation. Cathepsin B and L activity was mainly present in the microsomal fraction of control cells, but a part of this activity had shifted to the lysosomal fraction of differentiated cells. With the translocation of cathepsin B from the microsomal to the lysosomal fraction, the pro-enzyme form of cathepsin B was converted into the mature enzyme. These results suggest that the lysosomal pathway contributes to the degradation of specific proteins with cell differentiation. PMID- 2184045 TI - Biological properties and partial purification of a growth factor from porcine spleen. AB - 3T3-Fibroblast growth is enhanced in a dose-dependent way by a factor isolated from porcine spleen after limited proteolysis. The factor is not dialyzable and is stable for 5 min at 100 degrees C and at pH 2 at room temperature. Trypsin or collagenase treatment does not affect its biological activity. The stimulation of cell growth is independent of serum concentration in the culture medium but is accelerated by insulin supplement. The biochemical properties of this factor indicate a novel growth promotor different from other growth factors. PMID- 2184046 TI - Increased secretory activity and estradiol receptor expression are among other relevant aspects of MCF-7 human breast tumor cell growth which are expressed only in the absence of serum. AB - We compared the morphology, clonogenic ability, Percoll gradient distribution, estrogen receptor proteins, and interactions with mesenchymal cells in MCF-7 breast tumor cells grown in medium containing fetal calf serum and insulin (FCS I) or in a defined medium with insulin (ID) as the only growth factor. In the absence of serum and at densities below 5000-8000 cells/cm2, MCF-7 cells required epidermal growth factor, insulin, and thrombin. When cells reached a density of 23,000-26,000 cells/cm2, only insulin was necessary for optimal growth. In ID medium cells showed an enlarged Golgi apparatus and marked plasma membrane modifications, suggesting increased secretory activity. Moreover there was an increase in the release of protein products to the culture medium and a time dependent ability of these cells to form macrocolonies in soft agar. On the contrary, cells in FCS-I showed no Golgi complex and few plasma membrane modifications. In both culture media tight junctions, desmosomes, and tonofilaments were present. We investigated the effect of conditioned media from MCF-7 cells growing in FCS-I or ID on the growth of primary rat vaginal fibroblasts. The growth of these mesenchymal cells was stimulated by FCS-I medium and inhibited by ID medium. By contrast, the embryonic fibroblast (preadipocyte) line CHEF/18 was also stimulated by FCS-I for the first 48 h, but thereafter ceased growth and acquired lipid droplets and a differentiated morphology. With ID medium, CHEF/18 cells were only partially inhibited with no changes in morphology. The Percoll gradient profiles of ID cells showed the same six fractions of increasing density as recently described. However, there was a progressive increase in subpopulations with higher growth rates and a decrease in the relative amount of the most differentiated cells. A unique feature of the growth analysis of MCF-7 cells in the absence of serum is the increased expression of the estradiol receptor gene. These studies show that the growth and differentiated properties of tumor cells can depend upon the cellular environment and offer a model system in which to further study this modulation. PMID- 2184047 TI - Clinical value of a direct platelet suspension immunofluorescence test in adult idiopathic thrombocytopenic purpura. AB - 109 adult patients with ITP were tested with the direct platelet suspension immunofluorescence test (PSIFT) for platelet-associated immunoglobulins (PAIg). 88 patients (81%) had a positive direct PSIFT. The mean platelet level at the time of the test was 45.2 X 10(9)/l [corrected] (SD = 28.8) with no difference between PSIFT-positive and -negative groups. The results of direct PSIFT were of limited value in predicting patient outcome. The overall better prognosis of patients with a negative direct PSIFT compared to those with a positive result was statistically significant. The PSIFT negatives achieved complete remission more often than PSIFT positives; and they also showed a tendency for a better response to splenectomy and therapy with high-dose i.v.Ig. Moreover, all the 21 patients refractory to therapy with corticosteroids, splenectomy or i.v.Ig, were PAIg positives. PMID- 2184048 TI - Use of recombinant human granulocyte-macrophage colony stimulating factor in T lymphocytosis with granulocytopenia. PMID- 2184049 TI - [The interaction of the neuroendocrine and immune systems and the role of the opioid peptides in regulating immune homeostasis]. AB - The data on the central mechanisms of the immune system regulation and the role of opioid peptides in this process are summarized. The fact that the opioid component is involved in the regulation of the system of immunity predetermines the possibility of the influence on the immune system by means of the compounds possessing the opioid activity. This fact and also their low toxicity make the compounds promising for the development on their basis of original immunomodulators devoid of the disadvantages being intrinsic to the available drugs. PMID- 2184050 TI - [The effect of fenigidin (nifedipine) and verapamil on renin activity, the levels of ionized calcium and aldosterone in the blood plasma and on the hemodynamic indices of rats with spontaneous hypertension]. AB - Nifedipine and verapamil (10 mg/kg orally) were found to induce a significant increase of renin activity, a decrease of aldosterone and ionized calcium levels in blood plasma in spontaneously hypertensive rats. A preliminary administration of a hypertonic solution of sodium chloride decreased renin activity, ionized calcium and aldosterone levels that contributed to the enhancement of the hypotensive effect of calcium antagonists. It was established that nifedipine by its effect on the parameters of hemodynamics and the condition of renin angiotensin system as well as the blood plasma ionized calcium level is superior to verapamil. PMID- 2184051 TI - [The pharmacological regulation of physiological functions in space medicine]. AB - There are considered the physiological systems of the body which are the most sensitive to the action of weightlessness and are subject to pharmacological correction at different stages of a space flight. Particular emphasis is given to the development and practical use of the cardiovascular drugs, the agents for prevention of movement disease and also the agents influencing the metabolic processes and mineral saturation of the bony tissue. The possibility of using the drugs intended for the application during space flights and in medical practice is emphasized. PMID- 2184052 TI - [The use of the antipyrine test for studying microsomal drug oxidation]. AB - The data about the use of "antipyrine test" in clinical practice for studying the drug oxidation peculiarities are presented. The data characterize the main pharmacokinetic properties of antipyrine as a "metabolic marker" for quantitative estimation of the effects of inductors and inhibitors on the liver microsomal enzyme activity. The research methods are described and the data on the effects of different environmental factors on antipyrine metabolism are presented. The peculiarities of using the drug as a model for studying the effects of different environmental factors on the drug metabolism are formulated. PMID- 2184053 TI - Nursing in the Third World: teaching burn care in Ecuador. PMID- 2184054 TI - On the assembly mechanism of neurofilaments. AB - 1. Isolated individual components of the triplet of neurofilaments from bovine brain can reassemble to make filaments with a specific structure, contrary to the already reported result that NF-H and NF-M cannot make filaments alone but can only make filaments by co-polymerization with NF-L. 2. This result suggests an alternative mechanism of assembly of the neurofilaments in which individual components of the triplet make filaments first, and then these aggregate to form the intact neurofilaments. 3. The triplet components of neurofilaments are reduced to a monomeric form in 8 M urea and 1% beta-mercaptoethanol (beta-ME) solution. However, in the absence of beta-ME, a part of each component of the triplet was preserved as oligomeric forms. 4. Among them, a stable tetramer of NF L was isolated by DE-52 column chromatography using 6 M urea solution in the absence of beta-ME. 5. This results supports the hypothesis that this tetramer can be considered as a protofilament of the neurofilament structure. PMID- 2184055 TI - Stimulation of release of Gal beta 1-4GlcNAc alpha 2-6 sialyltransferase from the FAZA hepatoma cell line by dexamethasone and phorbol ester. AB - 1. Gal beta 1-4GlcNAc alpha 2-6 sialyltransferase was assayed in FAZA hepatoma cells and the cell culture medium following growth of cells in presence of dexamethasone and phorbol ester. 2. There was about a seven-fold increase in sialyltransferase activities in cells and medium in presence of dexamethasone with the maximum effect occurring at 10(-6)-10(-7) M dexamethasone. 3. The presence of 10(-6) M phorbol ester in the culture medium increased sialyltransferase activities in cells and medium by ca 40% over the values found with dexamethasone alone. 4. The use of the FAZA hepatoma cell line for studies on sialyltransferase is compared with the primary hepatocyte system reported on earlier (Woloski et al., 1986). PMID- 2184056 TI - Some aspects of metabolic adaptations in lipid metabolism during starvation are mimicked by epinephrine in rat adipocytes. AB - 1. The effects of fasting on the neutral lipid synthesis to insulin and/or epinephrine in isolated fat cells have been examined using [1-14C]glucose. 2. The ability of adipocytes from starved rats to synthesize fatty acids from both labeled substrates was markedly diminished compared to adipocytes from control rats. 3. The response of lipogenic stimulation to insulin at all concentrations tested was greatly diminished in adipocytes from 24 hr starved rats. 4. [1 14C]glucose utilization rates in the absence or in the presence of insulin were not significantly different in adipocytes from 24 hr starved rats as compared with control adipocytes, although basal and insulin stimulated glyceride-glycerol synthesis were significantly higher in starved adipocytes. 5. Epinephrine acutely inhibited [1-14C]acetate incorporation into fatty acids for insulin-stimulated lipogenesis in control adipocytes, in contrast, this lipolytic agent strongly increased [1-14C]glucose conversion to triacylglycerols. 6. In both cases, the differences in lipid synthesis capacities found in both nutritional states were abolished by epinephrine. PMID- 2184057 TI - Pyruvate dehydrogenase activation by insulin in human circulating lymphocytes and the possible pathway involved. AB - 1. The incubation of human fresh circulating lymphocytes with insulin leads to modifications in the behaviour of the pyruvate dehydrogenase complex (PDH) when the contact medium is supplemented with 50 microM Ca2+ and Mg2+. 2. To investigate the mechanism involved in the PDH responsiveness to insulin in circulating lymphocytes and the role of Ca2+ and Mg2+ in this process, the PDH activity was assayed in lymphocytes combined with insulin and/or a number of substances whose mechanism of action is partially known. 3. Of these some have been seen to mimick insulin effects on PDH, whereas other were tested for the first time in this study. PMID- 2184058 TI - Parathyroid hormone-related peptide in the human fetal uro-genital tract. AB - Using a polyclonal antiserum raised against the first 34 amino acids of human parathyroid hormone-related peptide (PTHrP), we have localized PTHrP throughout the uro-genital tract of the human fetus aged between 8 and 40 weeks. Staining was present in the developing mesonephros, metanephros, gonads and in both the adrenal cortex and medulla. In particular, the developing mesonephric and metanephric renal tubules were intensely positive. Using Northern hybridization analysis we have detected a complex pattern of PTHrP mRNA transcripts ranging in size from 1.4 to 4.5 kb in early second trimester human fetal kidney. The presence of PTHrP in the mesonephros and metanephros provides evidence for a role for PTHrP in the regulation of fetal calcium metabolism. However, its presence in the gonad and adrenal gland invites the possibility of a wider role for PTHrP. PMID- 2184059 TI - Characterization and expression of a Xenopus ras during oogenesis and development. AB - We have characterized a cDNA which contains the entire coding sequence of a Xenopus laevis ras protein. The deduced amino acid sequence reveals a strong homology (92%) to human Ki-ras 2B protein. ras expression has been studied both qualitatively and quantitatively during Xenopus development. ras is expressed as a maternal mRNA in oocytes and early embryos at a level up to 1.5 x 10(7) copies per mature oocyte, corresponding to the level of ras mRNA found in 4 x 10(5) somatic growing cells. This level remains constant throughout the first rapid cleavage stages of the blastula before the midblastula transition (MBT). After this stage, the amount of ras RNA decreases gradually until the hatching tadpole stage, when a new zygotic expression is detected in the embryo. From that stage, a constitutive amount of 30-50 ras RNA transcripts per embryonic cell is registered, as observed in Xenopus proliferative somatic cells. The 23-kDa Xenopus ras protein has also been identified by both specific monoclonal antibody and in vitro transcription-translation experiments. It is expressed in oocytes before maturation, indicating that maturation is not the trigger for ras expression. The expression of Xenopus ras at a high level during oogenesis and early development suggests a major function of this gene both in meiosis and in mitosis events during embryonic development. PMID- 2184060 TI - Islet amyloid polypeptide amide causes peripheral insulin resistance in vivo in dogs. AB - Islet amyloid polypeptide is a 37 amino acid hormone-like peptide which is the major protein component of islet amyloid deposits commonly found in patients with Type 2 (non-insulin-dependent) diabetes mellitus. Recent studies indicate that a physiologically active form of this peptide appears to be carboxyamidated and secreted from the insulin-producing beta cell. In order to clarify the possible in vivo actions of islet amyloid polypeptide, we have studied the effects of synthesized islet amyloid polypeptide-amide on peripheral glucose utilization by performing hyperinsulinaemic euglycaemic glucose clamp studies on dogs. Exogenously administered islet amyloid polypeptide-amide (an infusion from 1.0 to 100 micrograms.kg-1.h-1, over 2 h) inhibited the insulin-stimulated glucose disposal rate in a dose dependent manner. Twenty-five micrograms.kg-1.h-1 of islet amyloid polypeptide-amide infused via a peripheral vein significantly lowered the glucose disposal rate by 20% (from 17.4 +/- 1.7 to 14.4 +/- 1.7 mg.kg 1.min-1, n = 5, p less than 0.01). These findings suggest that islet amyloid polypeptide-amide causes peripheral insulin resistance in vivo. PMID- 2184061 TI - Do angiotensin converting enzyme inhibitors represent a progress in hypertension care in diabetes mellitus? PMID- 2184062 TI - In vitro activity of biosynthetic human diarginylinsulin. AB - In diarginylinsulin two arginine residues are located at the C-terminal end of the B-chain (ArgB31 and ArgB32). This accounts for a shift of the isoelectric point from pH 5.4 in native insulin to pH 7.0 in diarginylinsulin leading to pharmacodynamic characteristics of an intermediate acting insulin when administered s.c. as pH 4.0-5.0 solution. We have investigated insulin receptor binding and biological activity of biosynthetic human diarginylinsulin in human adipocytes and compared to native insulin and proinsulin. Association- and dissociation studies of insulin receptor binding revealed no differences for diarginylinsulin and native insulin. In competition studies under steady-state binding conditions, half-maximal displacement of tracer occurred at 352 +/- 33 pmol/l, 337 +/- 32 pmol/l and 3640 +/- 480 pmol/l for diarginylinsulin, insulin and proinsulin, respectively. The biologic potency of human diarginylinsulin was evaluated by the ability to stimulate D-glucose transport and by the assessment of the antilipolytic activity. Activation of D-glucose transport was half-maximal at 49.6 +/- 5.4 pmol/l (diarginylinsulin), 44.8 +/- 5.8 pmol/l (insulin) and at 476.7 +/- 134.3 pmol/l (proinsulin). Half-maximal inhibition of lipolysis occurred at 13.9 +/- 3.4 pmol/l, 15.4 +/- 2.9 pmol/l and 138.4 +/- 38.6 pmol/l, respectively. In conclusion, diarginylinsulin has almost identical insulin receptor binding characteristics and full biological activity in vitro compared to native insulin. This pharmacodynamically intermediate acting insulin preparation is therefore of potential therapeutical value. PMID- 2184063 TI - Insulin-driven erythropoiesis may underlie impairment of erythrocyte deformability in hyperinsulinaemic, hyperglycaemic ob/ob-mice. AB - The circulating erythrocytes in hyperglycaemic and hyperinsulinaemic obese (ob/ob) mice are enlarged with a decreased erythrocyte filtrability and an abnormally low resistance to osmotic stress. These changes probably reflect aberrations of erythropoiesis, as evidenced by endhanced staining for iron in the bone marrow, reticulocytosis, and increased erythrocyte volume fraction. Mature erythrocytes, reticulocytes, and late-phase basophilic erythroblasts were found to have larger diameters than their counterparts in control mice while myelopoiesis appeared to be unaffected. The average erythrocyte also displayed an increased cell volume and a decreased haemoglobin concentration. It is suggested that the stimulation of the erythroid cell line in ob/ob-mice might be a consequence of the hereditary hyperinsulinaemia. PMID- 2184064 TI - Ocular complications in the old and glucose-intolerant genetically obese (fa/fa) rat. AB - Genetically obese fatty (fa/fa) male rats with abnormal oral glucose tolerance associated with initial hyperinsulinaemia as well as control lean (FA/FA) rats were investigated for the development of retinal microangiopathies. The animals were kept on a standard or sucrose supplemented diet. When tested at 60 weeks, the glucose intolerance of fa/fa rats was accompanied by an insulin response that was now either comparable to that of lean rats (standard diet) or close to nil (sucrose supplemented diet). At killing (68 weeks of age), retinal vasculature was examined by electron microscopy and morphological changes were quantitatively assessed by ultrastructural morphometry. A retinal microangiopathy was observed in all mutant animals which was more pronounced in the sucrose fed group, and which was characterized by: (1), an increase in focal thickenings and in nodules of the basement membrane adjacent to the perivascular glial cells: (2), a decrease in the number of pericyte nulei with concomitant signs of early degenerative cytoplasmic changes of pericytes; (3), an increase in the pinocytic activity of endothelial cells, indicative of presumptive changes in vascular permeability; (4), an increase in the number of intercellular endothelial junctions; (5), the presence of numerous stimulated platelets within capillaries. The fa/fa rat may thus be considered as a suitable model for studying the pathophysiology of ocular complications, in particular retinopathy accompanying non-insulin-dependent diabetes. PMID- 2184065 TI - The activity of the renin-angiotensin-aldosterone system before and during submaximal bicycle exercise in relation to circulatory catecholamines in patients with type 1 (insulin-dependent) diabetes mellitus. AB - To evaluate the renin-angiotensin-aldosterone system in relation to circulatory catecholamines, we determined renin activity, angiotensin II, aldosterone, adrenaline, and noradrenaline in plasma before and during a submaximal bicycle exercise test in 23 Type 1 (insulin-dependent) diabetic patients (aged 19-57 years, mean 37; duration of diabetes 2-32 years, mean 16), 17 with signs of cardiac autonomic neuropathy, and in 18 healthy non-diabetic subjects (aged 24-41 years, mean 29). At rest, Type 1 diabetic patients showed significantly lower aldosterone values than control subjects (0.14 +/- 0.02 nmol/l and 0.22 +/- 0.02 nmol/l; p less than 0.01) while renin activity (1.0 +/- 0.1 nmol.l-1.h-1 and 0.9 +/- 0.1 nmol.l-1.h-1) and angiotensin II (14 +/- 1 nmol/l and 18 +/- 2 nmol/l) did not differ significantly between patients and control subjects. During exercise, increments (increase from the resting value to the value at 80% of maximal working capacity) in renin (1.5 +/- 0.4 nmol.l-1.h-1 and 3.7 +/- 0.5 nmol.l-1.h-1; p less than 0.001), angiotensin II (28 +/- 8 nmol/l and 60 +/- 8 nmol/l; p less than 0.001), aldosterone (0.16 +/- 0.04 nmol/l and 0.25 +/- 0.05 nmol/l; p less than 0.05), adrenaline (1.96 +/- 0.49 nmol/l and 2.92 +/- 0.51 nmol/l; p less than 0.05), and noradrenaline (12.01 +/- 1.25 nmol/l and 18.74 +/- 1.45 nmol/l; p less than 0.01) were significantly lower in the patients than in control subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2184066 TI - Permanent neuropsychological impairment after recurrent episodes of severe hypoglycaemia in man. AB - Seventeen Type 1 (insulin-dependent) diabetic patients with a history of recurrent and severe hypoglycaemia and Type 1 diabetic patients with no severe hypoglycaemia were compared as regarded performances in tests of neuropsychological functioning. To test the hypothesis that recurrent severe hypoglycaemia gives rise to permanent cognitive impairment, the study group was selected among those patients who had met with repeated attacks over the last three years or more as identified by a questionnaire among almost 600 insulin treated diabetic patients. The comparison group without known severe reactions were comparable to the study group with respect to type of diabetes, sex, age, age at onset, duration of diabetes, socio-economic parameters, and prevalence of neuropathy and retinopathy. The results indicate that Type 1 diabetic patients with recurrent severe hypoglycaemia scored lower than those without severe hypoglycaemia in tests of motor ability, short-term and associative memory and visuospatial tasks assessing ability in general problem-solving. Type 1 diabetic patients with severe hypoglycaemia also displayed a higher frequency of perspective reversals suggesting frontal-lobe involvement. These data can be interpreted in two ways. One interpretation implies that the cognitive impairment of Type 1 diabetic patients with severe hypoglycaemia reflects a selection factor, the other that recurrent episodes of severe hypoglycaemia result in permanent cognitive impairment. PMID- 2184067 TI - Increased glucose carbon recycling in severely insulin deficient type 1 (insulin dependent) diabetic subjects. AB - Six Type 1 (insulin-dependent) diabetic subjects were studied in order to determine the contribution of recycling of glucose carbon to the overproduction of glucose which is characteristic of the fasting hyperglycaemia produced by insulin withdrawal. The subjects were studied on two occasions, once after an overnight insulin infusion and once following 24 h of insulin withdrawal. The difference in turnover rates of 1-14C-glucose and 3-3H-glucose was used as a measure of glucose recycling. Insulin withdrawal caused a marked metabolic derangement with a rise in non-esterified fatty acids from 0.69 +/- 0.23 to 1.11 +/- 0.21 mmol/l (mean +/- SEM, p less than 0.05), total ketones from 0.27 +/- 0.06 to 2.06 +/- 0.51 mmol/l (p less than 0.01), cortisol from 341 +/- 43 to 479 +/- 31 nmol/l (p less than 0.05) and growth hormone from 1.1 +/- 0.3 to 19 +/- 5 mu/l (p less than 0.05). Glucose turnover rose from 13.8 +/- 2.3 mumol.kg-1.min-1 at a glucose of 6.9 +/- 0.7 mmol/l in the insulin infused study to 25.8 +/- 4.4 mumol.kg-1.min-1 (p less than 0.05) at a glucose of 16.4 +/- 0.7 mmol/l in the insulin withdrawn study. Recycling also rose from 3.0 +/- 0.4 mumol.kg-1.min-1 to 9.4 +/- 2.2 mumol.kg-1.min-1 (p less than 0.05) when insulin withdrawn, accounting for 23 +/- 3% and 36 +/- 3% of glucose turnover, respectively. We conclude that in the severely insulin deficient Type 1 diabetic subject recycling of glucose carbon is a major contributor to the excess glucose production. PMID- 2184068 TI - Evidence for a hyperglycaemia-dependent decrease of antithrombin III-thrombin complex formation in humans. AB - In the presence of increased levels of fibrinopeptide A, decreased antithrombin III biological activity, and thrombin-antithrombin III complex levels are seen in diabetic patients. Induced-hyperglycaemia in diabetic and normal subjects decreased antithrombin III activity and thrombin-antithrombin III levels, and increased fibrinopeptide A plasma levels, while antithrombin III concentration did not change; heparin was shown to reduced these phenomena. In diabetic patients, euglycaemia induced by insulin infusion restored antithrombin III activity, thrombin-antithrombin III complex and fibrinopeptide A concentrations; heparin administration had the same effects. These data stress the role of a hyperglycaemia-dependent decrease of antithrombin III activity in precipitating thrombin hyperactivity in diabetes mellitus. PMID- 2184069 TI - No evidence for isotope discrimination of tritiated glucose tracers in measurements of glucose turnover rates in man. AB - Under non-steady-state conditions, glucose turnover rates determined with tritiated glucose tracers are often underestimated. To examine whether isotope discrimination or a tracer contaminant can contribute to this, we compared the turnover rates of unlabelled and tritiated glucose under isotopic steady-state conditions. The turnover rates were measured in 20 healthy subjects at two insulin concentrations (79 +/- 3 mU.l-1 and 704 +/- 62 mU.l-1). Euglycaemia was maintained by infusing unlabelled glucose mixed with (3(3)H)- or (6(3)H)-glucose. In both studies, the isotopically determined glucose disposal rate was virtually identical to the exogenous glucose infusion rate (low insulin 7.66 +/- 0.48 vs 7.58 +/- 0.44 mg.kg-1.min-1, high insulin 13.36 +/- 0.74 vs 13.55 +/- 0.98 mg.kg 1.min-1). The individual values were correlated in both the low (r = 0.85, p less than 0.001) and high dose insulin (r = 0.81, p less than 0.001) studies. Tritiated glucose specific activities were also compared in arterialized and deep venous blood across forearm tissues during the high-dose insulin infusion. Glucose specific activities were similar in arterialized and deep venous blood when analysed with HPLC and conventional methods. In summary: (1) Under isotopic steady-state conditions the turnover rates of unlabelled and labelled glucoses are similar. (2) Unlabelled and labelled glucose are handled identically across forearm tissues. (3) We found no tracer impurity in our tritiated glucose preparations. We conclude that (3(3)H)- and (6(3)H)-glucose tracers can be used to reliably measure glucose turnover rates in man. PMID- 2184070 TI - Using insulin U 100 conversion to estimate the prevalence and problems of insulin treated diabetic patients in the Republic of Seychelles. PMID- 2184071 TI - How far should blood pressure be lowered? What is the importance of the J-curve phenomenon? PMID- 2184072 TI - [Evaluation of biological prostheses using the Doppler method]. PMID- 2184073 TI - [Current epidemiological characteristics of infectious endocarditis]. PMID- 2184074 TI - [Human alveolar echinococcosis. Epidemiologic hazard or immunologic incident?]. PMID- 2184075 TI - [Disinfection of endoscopic equipment: the desirable and the possible]. PMID- 2184076 TI - [Methods of functional exploration of chronic idiopathic constipation in adults]. PMID- 2184077 TI - [Metastatic splenomegaly revealing epidermoid carcinoma of the esophagus. Diagnosis by puncture directed by echography]. PMID- 2184078 TI - Endoscopic ultrasonography. PMID- 2184079 TI - Esophageal carcinoma: pre-operative staging and evaluation of anastomotic recurrence. AB - Survival after surgical resection of esophageal carcinoma is highly related to stage. The latest staging classifications (UICC/AJCC, 1987/1988) use the TNM system. Accumulating data show endoscopic ultrasonography (EUS) to be consistently more accurate than CT in pre-operative staging of depth of tumor invasion. Detailed images of the esophageal wall obtained by EUS allow accurate staging even in early cancer where CT is ineffective. EUS is also more accurate than CT in staging regional lymph nodes, but is less accurate than CT in staging distant metastases due to tumor stenosis in some patients and limited depth of field. EUS has also been shown to be accurate in diagnosing post-operative recurrence of cancer in the area of the surgical anastomosis. EUS represents a major advance in the clinical staging of esophageal cancer. PMID- 2184080 TI - Diagnosis of submucosal lesions of the upper gastrointestinal tract by endoscopic ultrasonography. AB - The use of endoscopic ultrasonography (EUS) in the diagnosis of submucosal upper gastrointestinal tract lesions was examined in 308 patients. Two-hundred ten submucosal tumors, 89 cases of esophagogastric varices, and 9 cases of non Hodgkin's lymphoma were found. EUS images were interpreted based upon a five layer EUS structure of the normal gastrointestinal wall. A characteristic EUS image was seen with leiomyoma, cysts, lipoma, and varices. EUS had an accuracy of 80% in staging nine cases of lymphoma. EUS is a valuable technique for the evaluation and diagnosis of submucosal upper gastrointestinal tract lesions. PMID- 2184081 TI - Endosonography in the clinical staging of esophagogastric carcinoma. AB - Endosonography (ES) was preoperatively performed in 113 patients with esophageal carcinoma (group 1) and in 84 patients with gastric carcinoma (group 2). Results of imaging and histology of resected specimens were correlated according to the new (1987) TNM classification. ES was accurate in assessing the depth of tumor infiltration. Overall accuracy of ES for group 1 was 89% and for group 2 83%. Early carcinomas could be distinguished from advanced cancers. ES was accurate in diagnosing lymph node metastases (sensitivity group 1 95% and group 2 87%) but less accurate in defining inflammatory changes of lymph nodes (specificity group 1 50% and group 2 48%). The incidence of lymph node metastases increased with progression of the depth of tumor infiltration. ES is not accurate for staging distant metastasis due to the limited penetration depth of ultrasound. Thus, additional transcutaneous ultrasound or computed tomography is necessary. Routine ES-guided cytology of lymph nodes may further enhance the diagnostic accuracy of ES. PMID- 2184082 TI - Assessment of portal hypertension by endoscopic ultrasonography. AB - Endoscopic ultrasonography (EUS) was performed in 40 patients with portal hypertension (PH) and in 48 control subjects. The azygous, splenic, mesenteric, and portal veins were displayed in both groups. However, esophageal and gastric varices, periesophageal and perigastric collateral veins, and submucosal gastric venules were displayed only in patients with portal hypertension. EUS was inferior to endoscopy in detecting and grading esophageal varices (p less than 0.0005), but EUS was superior in the detection of varices in the fundus of the stomach (p less than 0.0005). Detection of periesophageal veins by EUS increased with increasing diameter of esophageal varices at endoscopy (57% in grade 1, 89% in grade 2, and 100% in grade 3), and there was a direct correlation between endoscopic grade and the diameter of the periesophageal collateral veins at EUS. The diameter of the azygous vein by EUS at its distal and proximal margins was significantly greater in patients with PH (p less than 0.001); the EUS diameter of the azygous vein was significantly larger with variceal grade 2 compared with grade 1 (p less than 0.02 and p less than 0.01, respectively). In portal hypertensive gastropathy, endoscopic and EUS detection were coincident. No correlation was found between the presence of portal hypertensive gastropathy, endoscopic grade of esophageal varices, and detection of gastric varices at EUS. PMID- 2184083 TI - Endoscopic ultrasonography in the diagnosis of pancreatic tumors. AB - Endoscopic ultrasonography (EUS) can provide high resolution images of the pancreatic parenchyma. Complete visualization of the pancreas requires scanning from positions in the duodenum and stomach. Current clinical experience indicates that EUS is a useful adjunct to standard imaging in the evaluation of suspected pancreatic tumors. Improvements in technique and instruments are necessary to broaden the clinical application of EUS in pancreatic disease. PMID- 2184084 TI - Endoscopic ultrasonography in the evaluation of colon and rectal disease. AB - Endosonography of the colon has until recently been limited to examination of the rectum. Rigid and flexible instruments are currently available which allow for detailed images of the rectal wall. Comparative studies suggest that endosonography may be more accurate than computed tomography in the preoperative staging of rectal carcinoma. Recently, an ultrasound colonoscope has been developed which allows for visual examination, biopsy, and endosonography throughout the colon. Experience with this technique is limited and its role in the evaluation of colonic disease has not yet been determined. Further comparative trials are needed to more fully define the role of endosonography in the diagnosis of colorectal disease. PMID- 2184085 TI - Endoscopic ultrasound probes. AB - Ultrasound probes are being developed as alternatives to dedicated ultrasound endoscopes. These probes have been designed to pass through the instrument channel of ordinary fiberoptic or video endoscopes. We have developed a 20-MHz mechanical linear probe for use within the upper gastrointestinal tract, pancreatic duct, biliary tree, and colon. Rotational mechanical sector scanning probes as well as phased array probes are also being developed. Ultrasound probes are best used for high resolution imaging of focal endoscopically visible lesions. Endoscopic visualization enables direction of the probe to the lesion of interest. Unlike dedicated ultrasound endoscopes, ultrasound probes do not screen large areas of tissue and do not have deep penetration. Ongoing research will help define the indications for use of these probes and should lead to further refinements in their design. PMID- 2184086 TI - [Neocytapheresis]. PMID- 2184087 TI - A major cysteine proteinase is developmentally regulated in Trypanosoma cruzi. AB - Epimastigotes of different stocks of Trypanosoma cruzi contain similar levels of proteinase activity on azocasein; amastigotes and trypomastigotes contain 10-fold lower levels of this proteolytic activity, which seems, therefore, to be developmentally regulated. The proteinase could be detected as a broad band, centered at about 60 kDa, which in some cases resolved into two close bands, in (a) SDS-polyacrylamide gels containing fibrinogen, and (b) Western blots probed with a polyclonal rabbit antiserum prepared against purified cysteine proteinase. No proteinase activity was observed at molecular weights lower than 55 kDa. The results show that the enzyme previously purified is the major cysteine proteinase present in epimastigotes of all stocks of T. cruzi tested. PMID- 2184088 TI - Two novel transferable extended-spectrum beta-lactamases from Klebsiella pneumoniae in Tunisia. AB - Two novel beta-lactamases conferring multiresistance to antibiotics including oxyimino beta-lactams have been identified in two nosocomial K. pneumoniae strains isolated in Tunis in 1986 and 1988. Both enzymes were encoded by ca. 150 kilobase plasmids. Donor and transconjugant strains producing these enzymes exhibited highly similar pattern of resistance (CTX phenotype) to beta-lactams including penicillins and oxyimino beta-lactams e.g. cefotaxime, ceftriaxone, ceftazidime, and aztreonam. High and variable synergy (16 to 1066-fold) was obtained when combined to 0.1 microgram/ml of clavulanate (beta-lactamase inhibitor). The isoelectric points of these two enzymes were 5.4 and 6.4. These beta-lactamases differed from TEM types by hydrolysis for cefotaxime or ceftriaxone but were inhibited by clavulanate and cloxacillin. DNA hybridization studies suggested that that the genes of these enzymes may be derived from genes encoding TEM-type enzymes. PMID- 2184089 TI - Induction of sexual agglutinability by unsaturated fatty acids in Saccharomyces cerevisiae. AB - Agglutinins in S. cerevisiae are necessary for mating, for recognition between cells of opposite mating type. The mode of agglutinin synthesis is altered by the growth temperature and by the carbon source, from constitutive to inducible synthesis and vice versa. Some of the unsaturated fatty acids tested induced synthesis of agglutinins in cells grown at an elevated temperature, even in the absence of the pheromone. However, synthesis of agglutinins in glycerol-grown cells, that are inducible by the pheromone, was not induced by linolenic acid. Hence, the change in the mechanism of regulation of agglutinability produced by differences in temperature probably differs from that produced by differences in carbon source. PMID- 2184090 TI - Immunological characterization of the Prochlorothrix hollandica and Prochloron sp. chlorophyll a/b antenna proteins. AB - Polyclonal antibodies were prepared against the major antenna chlorophyll (Chl) a/b-binding protein from the prokaryote Prochlorothrix hollandica (Burger-Wiersma et al. (1986) Nature (Lond.) 320, 262-264). Immunoblotting experiments on Triton X-114 phase-partitioned P. hollandica thylakoids revealed that the antibody recognizes intrinsic membrane polypeptides of 33 and 30 kDa, and immunocytochemistry of P. hollandica thin sections showed that the antibody preferentially decorates the thylakoid. The antibody was immunopurified against a LacZ fusion protein produced in Escherichia coli by an immunopositive phage clone retrieved from a lambda ZAP expression library. This purified antibody crossreacted to both the 33 and 30 kDa polypeptides, indicating that these proteins are either structurally related products of different genes, or modified forms of the same gene product. Whereas immunological crossreactivity of Prochlorothrix antibody to the major LHC-II Chl a/b antenna of maize could not be detected, the immunopurified antibody reacted strongly to the major 34 kDa Chl a/b antenna protein from the prokaryote Prochloron sp. (Lewin (1975) Phycologia 14, 153-160). These data confirm the structural similarity of the prochlorophyte photosynthetic antenna systems. PMID- 2184091 TI - Genetic linkage and complex diseases, with special reference to psychiatric disorders. AB - Recent linkage findings for psychiatric disorders, in particular schizophrenia, manic-depression, and Alzheimer disease, have raised a number of important conceptual issues regarding the genetic etiology of these diseases, as well as the appropriate interpretation of linkage results in studying complex diseases. Perspectives on mode of inheritance, genetic heterogeneity, and phenotypic variation are given. PMID- 2184092 TI - Commingling and segregation analyses: comparison of results from a simulation study of a quantitative trait. AB - Commingling analysis is commonly used to provide preliminary evidence for a single genetic locus with a major effect on the quantitative trait of interest. In this paper, the effectiveness of commingling analysis as a screening technique to identify samples for segregation analysis is assessed by applying both commingling and segregation analyses to samples of simulated pedigree data in which a major locus is segregating in the presence of polygenes and an individual specific environmental effect. Under the circumstances simulated here, there is evidence for a single locus from segregation analysis but not from commingling analysis in at least 20% of the samples. No more than 2% of the samples provided evidence for commingling but not for segregation of a single locus. Comparisons of the samples that give evidence for both commingling and segregation, evidence for one but not the other, and no evidence for either show that evidence for commingling depends on the distributional characteristics of the trait in the sample, while support for the single locus from segregation analysis depends on both the distributional characteristics as well as the transmission of the rarer allele from parents to offspring. Since lack of commingling does not rule out the existence of a single locus in the realistic situations considered here, commingling analysis has limited usefulness as a screening technique for the presence for a single locus. In contrast, evidence for commingling does suggest the possibility that a single locus has a major effect on the trait and commingling analysis can provide guidance in the choice of initial parameter estimates for segregation analysis. PMID- 2184093 TI - Estimation of individual genetic and environmental factor scores. AB - Implicit in the application of the common-factor model as a method for decomposing trait covariance into a genetic and environmental part is the use of factor scores. In multivariate analyses, it is possible to estimate these factor scores for the communal part of the model. Estimation of scores on latent factors in terms of individual observations within the context of a twin/family study amounts to estimation of individual genetic and environmental scores. Such estimates may be of both theoretical and practical interest and may be provided with confidence intervals around the individual estimates. The method is first illustrated with stimulated twin data and next is applied to blood pressure data obtained in a Dutch sample of 59 male adolescent twin pairs. Subjects with high blood pressure can be distinguished into groups with high genetic or high environmental scores. PMID- 2184094 TI - Using factor scores to detect G X E interactive origin of "pure" genetic or environmental factors obtained in genetic covariance structure analysis. AB - Moment expressions for individual factor scores can serve as simple tests for the presence of a particular class of interaction factors that are disguised as pure genetic and/or environmental factors. That is, individual genetic and environmental factor scores may be used to construct fourth-order moments of these factors in order to test whether a common genetic or environmental factor in the multivariate genetic factor model is in fact of the interactive origin concerned. Expected fourth-order moments are derived for cases with and without interaction. Application of fourth-order moments of factor scores to detect interactive origin of common factors is illustrated with simulated twin data. PMID- 2184095 TI - The evolution of mental disturbances in the concentration camp syndrome (KZ syndrom). AB - As a result of long-term clinical research on former prisoners of the Nazi concentration camps, I analyzed the evolution of the clinical and psychopathological pattern of the KZ-syndrome. One can differentiate the following characteristic phases: psychosomatic inanition, latency of disease, personality and adaptation disturbances, a pseudo-neurotic and depressive phase, premature aging, and an organic phase. The stigma of KZ-syndrome is present in a second generation in different forms: personality disturbances, emotional and/or social immaturity, social disadaptation, higher frequency of neurotic states, divorce, alcoholism, and suicide. The camp stress has left in human nature traces so painful that they cannot disappear when the generation of former prisoners is gone. PMID- 2184096 TI - [The art of Toulouse-Lautrec and medicine]. AB - After mentioning the numerous designs done by Henri Toulouse-Lautrec, in 1891, in Pean's surgical department, the author presents and explains a lithography published in 1897 in Georges Clemenceau's book "Au pied du Sinai". The particular story it was to illustrate relates "how I became presbytic" ("Comment je devins presbyte") and shows the ophthalmologist Mayer prescribing reading glasses to Clemenceau. PMID- 2184097 TI - [The Graefe memorial stone--in memory of A. von Graefe's contributions in Heiden]. AB - Between 1859 and 1869, Albrecht von Graefe used to spend some weeks in September in Heiden, a small health resort in Eastern Switzerland. During his "holidays", however, the hotel "Freihof", where he lived, was transformed into a most active unit of ophthalmic surgery. A memorial stone, rediscovered and restored thanks to the endeavour of Professor Peter Speiser of St. Gallen, remembers this episode, which was of some importance not only for local tourism, but also for the young Swiss ophthalmology of the time. PMID- 2184098 TI - [Adolf Faller: anatomist and medical historian. 1913-1989]. PMID- 2184099 TI - [Michel de Montaigne (1533-1592): report of a case of not perceiving own blindness]. AB - In the second book of the Essais towards the end of the twelfth chapter Montaigne mentions a nobleman who does not take note of his blindness. This case of not noticing his own blindness is presumably the first ever described. It belongs to the complex of anosognosia symptoms among which must be emphasized the Anton syndrome. The invalidity described by Montaigne means for him a crucial point of his critique of senses and thus of his doctrine of natural cognition. PMID- 2184100 TI - [Felix Platter (1536-1614) as ophthalmologist]. AB - Felix Platter, physician and anatomist, had a keen interest in ophthalmology, too. By his wife, he was related to a family of surgeons; this may have brought him into closer contact with eye diseases and their cure. Platter was the first physician to attribute the sensory power of the eye to the retina and a purely optical function to the lens (humor crystallinus). The present author mentions two original observations of his: the symptomatology of posterior vitreous detachment (observed in his own myopic left eye) and a case of blindness due to compression of the optic nerves by a cranial tumour (tuberculoma). In a more comprehensive way, he discusses Platter's ideas on cataract (suffusio) and its treatment. Platter observed congenital cataract and was the first to notice that professional working near a fire (as in the case of alchemists!) may eventually lead to cataract (glass-workers' cataract, according to modern terminology). PMID- 2184101 TI - [Muscae volitantes--from early observations to Purkinje's explanation]. AB - The subjective visual phenomena known as "muscae volitantes" ("floating flies") were already known to the Greeks. Galen (2nd c. A.D.) explained them within his theory of vision as circumscript condensations of the aqueous. This opinion prevailed in Arab medicine and even in the science of the Renaissance and later. When, in the 17th c., Galen's theory, according to which the crystalline lens was the organ of visual perception, was replaced by Kepler's insight that the image of the outer world is formed on the retina, scholars such as Dechales and Morgagni came near the truth. In 1823, Purkine identified the muscae as opacities floating in the vitreous. PMID- 2184102 TI - [Carl Gustav Carus (1789-1869) and his single ophthalmologic publication]. AB - Carl Gustav Carus is the most important personality in medicine in Dresden in the first half of the 19th century. He is well known for his manifold activity as a doctor, scientist and philosopher as well as a landscape painter of the romantic period. His literary output is estimated at about 25,000 printed pages. There is just one paper which touches ophthalmology and teratology: in 1842, Carus described the monstrous head of a pig with cyclopia. The discussion follows an idealistic line with comparative anatomical studies in fauna and flora. PMID- 2184103 TI - [Friedrich August von Ammon (1799-1861) and Dresden ophthalmology in the 1st half of the 19th century]. AB - Friedrich August von Ammon of Dresden took a considerable part in shaping ophthalmology into a scientifically and clinically independent part of medicine, thus inserting himself into the great development of the specialty during the first half of the 19th century. In particular, he investigated the ontogeny of the human eye as well as its pathological anatomy. He edited journals, published monographs, created a school of his own and gained in this way far-reaching influence. As a practitioner, a teacher and a physician-in-ordinary to the King of Saxony, he maintained the tradition of an earlier ophthalmologist of Dresden: Georg Bartisch. PMID- 2184104 TI - [Carl Wilhelm von Zehender (1819-1916)--authentic data from his life]. AB - The life and work of Carl Wilhelm von Zehender are discussed in the light of recent information. As a pupil and friend of Albrecht von Graefe, he took part in the foundation of the Heidelberg Ophthalmological Society, which was, right from its start, an international association. He was the first editor of "Klinische Monatsblatter fur Augenheilkunde" (1863). In 1862, he was nominated professor of ophthalmology and otology at Berne, Switzerland, but already in 1866, he accepted a call to the newly created chair of ophthalmology at Rostock, Mecklenburg. There, he initiated ophthalmic microsurgery and--in the field of social medicine- scientific expert judgment of damage to the eyes. Hirschberg's rather depreciating criticism of von Zehender appears no longer valid. PMID- 2184105 TI - [History of photosurgery of the eye]. AB - Survey of the development of heliocautery from Antiquity to the 18th century. In art, photocoagulatin of a human eye (in order to destruct it) is, for the first time, represented in 1817 by Hieronymus Hess of Basel. A full account is given of (a) Wilhelm Werneck's therapeutic coagulations (1835): rupturing of cataract by focussed light (sun, phosphorus); (b) Maximilian Adolf Langenbeck's "insolation" of corneal, pupillary and retinal lesions and of traumatic cataract (1859); (c) Vinzenz Czerny's coagulation experiments on the retina of various animals (1867, 1882). J. Moron-Salas was the first to try photocoagulation of retinal tears (1946), but the actual initiator of modern ophthalmic photocoagulation therapy is Gerhard Meyer-Schwickerath (1949). PMID- 2184106 TI - [Medieval ophthalmology in the St. Gallen monastery. 2]. AB - From the 9th century on, the abbey of St. Gallen had a hospital. Reports of miraculous cures and the prescriptions that have remained give us many informations about how eye diseases were treated. PMID- 2184107 TI - [100 years of the Mikulicz syndrome]. AB - Between 1888 and 1892, Mikulicz as well as Fuchs observed each a case of oculo salivary glandular syndrome. Ten years later, Heerfordt described uveitis complicated by swelling of the lacrimal and salivary glands. Within 100 years, the interpretation of this disease changed repeatedly and considerably: infection of particularly exposed organs--non-avirulent tuberculosis--salivotropic virus- Boeck's disease--allergic-hyperergic reaction--diencephalic and nervous dystrophy with segmental projection--(auto)immune disease--oculo-salivary complex including Sjogren's syndrome--all these were discussed as possible aetiologies. Short biographies of Johannes von Mikulicz-Radecki, surgeon at Austrian and Prussian universities; Ernst Fuchs, ophthalmologist of Vienna; Christian Frederik Heerfordt, a Danish ophthalmologist particularly fond of publicity. PMID- 2184108 TI - [From Tadini to Svjatoslav N. Fedorov. Difficulties of ophthalmologic surgery]. AB - In 1765/66, the oculist Tadini showed to Giacomo Casanova artificial lenses, which he planned to implant into human eyes after removing the cataract by extraction. About 1795, the oculist Casaamata tried to put into effect Tadini's idea. It was not before 1949, however, that H. Ridley implanted the first artificial lens, when he had found out that acrylic glass could serve the purpose. In 1960, Svyatoslav N. Fedorov implanted the first hand-made artificial lens in the USSR. His successful operation was discredited to be non physiological and antipavlovistic. He had to overcome many difficulties, but became important by promoting modern microsurgery of the eye in the USSR. Since 1974, he introduced his version of radial keratotomy to correct myopia surgically. Today Fedorov is managing a technical-scientific complex in Moscow with twelve branches throughout the Soviet Union and with 5500 employees. In this complex, his radial keratotomy should be used as standard treatment of visual defects, in spite of its controversial quality. For that reason Fedorov fails to export his special method, which might be an experimental stage towards new refractive therapies. PMID- 2184109 TI - [Epidemiology of malignant neoplasms in rubber industry workers (review of the literature)]. PMID- 2184110 TI - [The V.A. Obukh Central Institute of Occupational Medicine and Occupational Diseases and the prevention of occupational diseases during World War II (from the pages of history)]. PMID- 2184111 TI - [Principles of the diagnosis and treatment of epilepsy]. AB - The diagnostic and differential-diagnostic necessities that result from an epileptic seizure are presented in synoptic form: the most common cause of an initial attack is alcohol withdrawal, inflammatory processes or tumors. In known epileptics, irregular use (non-compliance) of the drugs prescribed--or an infection (GI tract infection with disordered absorption) may be the triggering factor. Attention is drawn to the importance of the determination of serum levels (of anti-epileptic drugs). The establishment of day profiles in known epileptics can reveal inadequate or irregular ingestion of prescribed drugs to be the causal factor. PMID- 2184112 TI - [Drug treatment of epilepsy]. AB - The presently preferred anticonvulsives in adults are carbamazepine and valproate. Before the age of 10 years valproate is a second-choice drug only, on account of its hepatotoxicity in patients of this age. Alternatives in generalized primary grand mal seizures are phenobarbital, possible also valproate and phenytoin; in petit mal seizures ethosuximide. At present, numerous substances are being tested for their suitability as anticonvulsives. Those at the most advanced stage of clinical testing are: gabapentine, lamotrigine, oxcarbazepine, progabide, vigabatrin. Among the adverse reactions, the hepatotoxicity of valproate is particularly topical, making comprehensive laboratory examinations mandatory; however, these tests have little prognostic value. During pregnancy the seizure frequency may change. In most patients, the blood levels of the anticonvulsives decrease, despite constant dosage. In the newborn vitamin K1 prophylaxis is mandatory to prevent bleeding. The use of anticonvulsives does not contraindicate nursing. PMID- 2184113 TI - Memoirs of FNS days. PMID- 2184114 TI - Frontier Nursing Service--sixty year study of nurse-midwifery: 1925-1985. PMID- 2184115 TI - Excessive in vitro bacterial lipopolysaccharide-induced production of monokines in cirrhosis. AB - The objective of this study was to analyze monokine production by peripheral blood mononuclear cells from patients with alcoholic cirrhosis. The capacity of peripheral blood mononuclear cells and purified monocytes from these patients to produce tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 was investigated. Spontaneous production of tumor necrosis factor alpha, interleukin 6 and interleukin 1 beta was similar in cirrhotic and healthy subjects, but serum levels of interleukin 6 (less than 2 U/ml vs. 9.5 +/- 3 U/ml) and tumor necrosis factor alpha (3.1 +/- 1.2 pg/ml vs. 12.0 +/- 1.2 pg/ml) were significantly higher in cirrhotic patients. However, peripheral blood mononuclear cells or purified monocytes from patients with alcoholic liver cirrhosis, stimulated in vitro with Escherichia coli lipopolysaccharide, displayed a marked increase of tumor necrosis factor alpha, interleukin 1 beta and interleukin 6 secretions compared with healthy controls. A striking feature of this overproduction was its reversibility as assessed by allowing cells to rest in vitro without lipopolysaccharide for 1 to 7 days before stimulation. In such conditions, tumor necrosis factor alpha and interleukin 6 secretions declined to levels present in healthy subjects in whom production remained stable, whereas interleukin 1 beta secretion markedly decreased in both groups to the point where no difference could be seen. This reversible oversecretion of cytokines after lipopolysaccharide stimulation, along with the lack of abnormality of spontaneous cytokine secretion, suggests that monocytes in these patients may have undergone an in vivo activation process analogous to a priming phenomenon. The in vitro activation with lipopolysaccharide may represent the correlate of in vivo endotoxemia observed during acute events such as sepsis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2184116 TI - Plasma membrane bleb formation and rupture: a common feature of hepatocellular injury. PMID- 2184117 TI - Cholesterol crystal nucleation: a decade-long search for the missing link in gallstone pathogenesis. PMID- 2184118 TI - AIDS update: an executive report. AB - Jackson Memorial Hospital, Miami, lost $5.6 million treating AIDS patients last year. Executives at the 1,246-bed public hospital project losses of more than $7 million in 1990. Jackson Memorial's experience is unfortunately all too typical of the effect that AIDS has had on public hospitals. But AIDS is not just a public hospital problem. The trend toward concentration of AIDS cases in public hospitals could have dire consequences for all hospitals in a community, say analysts. But the impact of AIDS on the health care community can be felt at a number of different levels. This executive report also takes an in-depth look at: How case management is being used--or misused--with AIDS patients. How much money state legislatures are allocating for AIDS and what the states are spending the funds on How executives are dealing with various liability issues. PMID- 2184119 TI - Physician creates network of cost-conscious colleagues. PMID- 2184120 TI - Centre d'etude du polymorphisme humain (CEPH): collaborative genetic mapping of the human genome. PMID- 2184121 TI - Temporal feature extraction and clustering analysis of electromyographic linear envelopes in gait studies. AB - A technique for automatically clustering linear envelopes of the EMG during gait has been developed which uses a temporal feature representation and a maximum peak matching scheme. This new technique provides a viable way to define compact and meaningful EMG waveform features. The envelope matching is performed by dynamic programming, providing qualitatively the largest numbers of matched peaks and quantitatively a minimum distance measurement. The resulting averaged EMG profiles have low statistical variation and can serve as templates for EMG comparison and further classification. PMID- 2184122 TI - Pulsed Doppler accuracy assessment due to frequency-dependent attenuation and Rayleigh scattering error sources. AB - All engineering measurements are subject to inaccurate and imprecise estimates, including the estimate of blood flow velocity. An assessment of specific error sources can minimize such uncertainties. Frequency-dependent attenuation and Rayleigh scattering are significant error sources for pulsed Doppler ultrasound because the transmitted ultrasonic signal has a finite width spectrum. The former causes a frequency downshift and the latter a frequency upshift, both of which are independent of the actual Doppler frequency shift. This communication evaluates these error sources through computer stimulation and compares the computed error to experimental data. PMID- 2184123 TI - Mechanisms of stress ulceration and implications for treatment. AB - The incidence of stress ulceration and its complications has decreased over the last decade significantly. The reason for this development is the better understanding of the protective mechanism of stomach and duodenum as well as the prophylactic treatment. This can be achieved by antacids, H2-blockers, and sucralfate, whereas prostaglandins are not effective. PMID- 2184124 TI - Overview of medical therapy of peptic ulcer disease. AB - Medical management of peptic ulcer disease continues to evolve with the recent introduction of new H2-receptor antagonists, prostaglandin analogs, and a proton pump inhibitor, and clarification of the relationship between suppression of gastric acidity and ulcer healing. Nizatidine and roxatidine acetate, the new H2 blockers, are safe and effective but do not appear to have new properties of clinical importance. The modes of action of omeprazole and the prostaglandins have been clarified. Omeprazole is a prodrug that is protonated and secured in the secretary canaliculus of the parietal cell where the active derivative covalently binds sulfhydryl groups of H+/K(+)-ATPase, thereby irreversibly and profoundly blocking acid secretion. Prostaglandins bind a receptor on the basolateral membrane of the parietal cell, releasing a protein that inhibits cyclic AMP, the second messenger of histamine-stimulated acid secretion. The ulcer-healing properties of prostaglandins can be attributed largely if not entirely to their inhibition of acid secretion. Antacids, on the other hand, may heal ulcers by effects other than acid neutralization, as the low-dose regimens that heal ulcers only weakly neutralize acid. The way in which sucralfate and colloidal bismuth heal ulcers remains unclear; they may do so through multiple effects including, in the case of bismuth, eradication of C. pylori. H2-receptor antagonists continue as first-line treatment for acute DU and GU and the prevention of recurrence. The antacid and sucralfate regimens are less convenient but safe and effective. Misoprostol has a disadvantageous safety profile relative to available agents but is effective in preventing NSAID-induced gastric ulcers. The efficacy of omeprazole in acid-peptic disease is established but the way in which it should be used is still unclear because of long-term safety concerns. PMID- 2184125 TI - Drug-induced changes of plasma gastrin concentration. AB - There is a significant inverse relationship between intragastric acidity and plasma gastrin concentration. All generally available gastric acid antisecretory drugs induce a release of gastrin into the circulation. The more potent the gastric antisecretory dosage regimen or drug, the greater the rise of plasma gastrin concentration. The drug-induced rise of plasma gastrin concentration is of no direct clinical concern, although it may be partly responsible for the phenomenon of tolerance to H2-blockade. Drug-induced hypergastrinemia could stimulate the proliferation of certain cell lines associated with the gastrointestinal tract, for example, the gastric epithelium, ECL cells, or colonic neoplasms. PMID- 2184126 TI - Bleeding peptic ulcer. Epidemiology and nonsurgical management. AB - Bleeding peptic ulcer remains an important problem, particularly for the elderly. Recognition of the rule of nonsteroidal anti-inflammatories in bleeding ulcer and employment of endoscopic therapeutic modalities offer promise that morbidity and mortality from bleeding ulcer may be reduced. PMID- 2184127 TI - The relationship between nonsteroidal anti-inflammatory drug use and peptic ulcer disease. AB - It has become increasingly recognized that nonsteroidal anti-inflammatory drug (NSAID) use is associated with serious gastroduodenal mucosal injury that can eventuate in upper gastrointestinal bleeding or perforation. This article discusses the lack of predictive value of studies administering NSAIDs to normal volunteers. The new data concerning prevention and treatment of chronic NSAID ulcers is also discussed. PMID- 2184128 TI - Campylobacter pylori and its role in peptic ulcer disease. AB - In almost all patients with genuine nondrug-induced duodenal or gastric ulcer there is evidence of gastric Campylobacter pylori colonization and concomitant inflammation. C. pylori is only demonstrable in the duodenal cap when there is "gastric mucus metaplasia." Suppression or eradication of C. pylori with antibiotic therapy may accelerate duodenal ulcer healing. The relapse rate of duodenal ulcer is less after temporary clearing or permanent eradication of C. pylori. As eradication of C. pylori reduces or eliminates gastric (and duodenal) inflammation, this renders the gastroduodenal mucosa less susceptible to reulceration. Interference with C. pylori status presumably explains the retardation of relapse of duodenal ulcer healing with colloidal bismuth subcitrate. PMID- 2184129 TI - Zollinger-Ellison syndrome. Recent advances in the management of the gastrinoma. AB - Because of increasingly effective oral antisecretory agents, gastric acid hypersecretion is now able to be controlled in all patients with Zollinger Ellison syndrome with the result that the natural history of the gastrinoma is becoming the major determinant of long-term survival. In this article recent advances in the management of the gastrinoma itself are reviewed, including results with new modalities such as intraoperative ultrasound, MRI, and selective gastrin sampling to localize gastrinoma in patients with Zollinger-Ellison syndrome, as well as recent results of the treatment of metastatic and localized gastrinomas. PMID- 2184130 TI - Control of pepsinogen synthesis and secretion. AB - The heterogeneous group of proteinases known as pepsinogens are synthesized, stored, and upon appropriate stimulation released from gastric mucosal chief cells. Under the acidic conditions of the lumen of the stomach, the proenzymes, pepsinogens, are converted to "pepsin", which plays an important physiologic role as a digestive enzyme. The potential roles for pepsin in upper gastrointestinal diseases such as gastric or duodenal ulcer and gastroesophageal reflux disease along with the recent development of in vitro gastric gland and isolated chief cell preparations have renewed interest in the study of the control of pepsinogen synthesis and secretion. In this article the authors briefly summarize current knowledge of the biology of pepsinogens and emphasize more recent findings concerning the control of the chief cell, which is related to the synthesis and secretion of pepsinogens in vitro. PMID- 2184131 TI - Experimental gastric and duodenal ulcers. Advances in pathogenesis. AB - New developments in the study of the pathogenesis of experimental gastric and duodenal ulcers indicate a complex multifactorial process leading to ulceration. The concept of gastric cytoprotection with prevention of hemorrhagic mucosal lesions by PG, SH, or other compounds without inhibiting acid secretion was discovered while investigating animal models of gastric erosions and ulcers. Subsequent research into the pathophysiology of gastric ulcer has been revitalized. New studies have demonstrated that the development or prevention of vascular injury in the gastric mucosa plays a crucial role in gastric mucosal injury and protection. The pathophysiology of experimental duodenal ulcer disease has shown that controlling gastric acid secretion is not the only approach to the prevention or treatment of this disorder. Data from human and animal experiments suggest that duodenal dysmotility contributes to the decreased neutralization of acid whether secreted at a normal or subnormal rate, in the duodenal bulb. Dopamine infusion corrected experimentally induced duodenal hypermotility, but other neurotransmitters may also be involved. Multidisciplinary investigations using experimental models of gastric and duodenal ulcers lead not only to the discovery of new concepts and pathogenetic mechanisms but also to the recognition of new chemicals that may exert gastroprotective and antiulcerogenic effects. PMID- 2184132 TI - Mucosal defense. New avenues for treatment of ulcer disease? AB - Ulceration likely occurs as a consequence of a progressive failure of the various components of mucosal defense. Present therapy for peptic ulcer is focused almost entirely on reduction of luminal "aggressive" factors. Future advances in the treatment of ulcer disease is likely dependent on our developing a better understanding of mucosal defense. PMID- 2184133 TI - Lack of immunomodulating effect of disulfiram on HIV positive patients. AB - Disulfiram (Antabuse (R)) is metabolized to two molecules of diethyldithiocarbamate, which has been reported to be an immunomodulating agent. In a double blind trial, 15 HIV antibody positive homosexual men were given daily doses of 100 mg or 400 mg of disulfiram or placebo, for 4 weeks. All had a CD4 count below 500 X 10(6)/l and/or a pokeweed mitogen response in a lymphocyte proliferation assay less than 50% of normal controls. None suffered from opportunistic infections. No significant effect of disulfiram on immunological, haematological, biochemical or clinical variables was observed in this short-term trial. PMID- 2184134 TI - In vivo enhancement of NK-cell activity by thymopentin. AB - Natural killer (NK) activities of fresh and IL-2-precultured peripheral blood mononuclear cells (PBMC) were investigated in 13 elderly subjects before and after thymopentin (TP-5) treatment and in 12 age-matched controls. The NK activity of fresh PBMC was found to be significantly higher in subjects given TP 5 at 50 mg s.c. three times per week for one month. Conversely, this type of treatment with TP-5 did not significantly modify the cytotoxic capacity of IL-2 precultured PBMC. PMID- 2184135 TI - Adjuvant treatment of operable stomach cancer with polyadenylic.polyuridylic acid in addition to chemotherapeutic agents: a preliminary report. AB - A randomized trial of polyadenylic.polyuridylic acid [poly(A).poly(U)] in addition to chemotherapy was undertaken in patients with stomach cancer following curative gastrectomy. They were randomized into a group of 108 patients receiving chemotherapy plus poly(A).poly(U) and a control group of 116 patients receiving chemotherapy alone. Chemotherapy consisted of injections of 5-fluorouracil, 12 mg/kg once weekly and adriamycin, 40 mg/m2 once every 3 weeks, continuously after operation. Poly(A).poly(U) was infused in a 100 mg dose, once a week six times from 5 days after the first injection of chemotherapeutic agents and 6 months later in a half dose similarly. At 55 months after initiation of the trial, the mean follow-up periods were 24 months for both groups. It has been revealed that patients who received the combined treatment postoperatively showed a lesser mortality and lower rate of recurrence, both reflecting significant increases in overall (P less than 0.05) and relapse-free (P less than 0.02) survivals as compared to those who received chemotherapy alone. This effect is more pronounced in patients having moderately advanced lymphnode involvement (N1) than in patients without (N0) or more advanced (N2) involvement. Thus, poly(A).poly(U) appears to be an effective agent when used postoperatively with chemotherapy in stomach cancers. PMID- 2184136 TI - Production of interleukin 1 from human monocytes stimulated by synthetic lipid A subunit analogues. AB - We have investigated that synthetic lipid A subunit analogues (GLA compounds) as well as E. coli type lipopolysaccharide (LPS) and synthetic lipid A (compound 506) are able to stimulate human monocytes to release IL-1 in vitro. Of monosaccharide-type GLA compounds, GLA-60 was found to be more active for the induction of IL-1 production than GLA-59 and GLA-27, and similar to that of LPS or compound 506. GLA-60 could induce not only the secretion of IL-1 into culture supernatant but also the expression of membrane-associated form of IL-1 in human monocytes. Furthermore, no detectable IL-2 activity was observed in the culture supernatant. These results show that synthetic lipid A analogues of low toxicity, in particular GLA-60, are active in inducing IL-1 production in human monocytes. PMID- 2184137 TI - Increase in specific antibody-forming cells in human tonsils after oral stimulation with D-53, a ribosomal vaccine. AB - Thirty subjects who had received an oral ribosomal vaccine to common bacteria of upper respiratory tract infections, and ten controls were tonsillectomized for recurrent infections or rhonchologic pathology. A three-step indirect immunofluorescence technique was used to identify and enumerate specific antibody forming cells (SAFC) in their tonsils. Plasma-cells specific of the four strains being constituents of the oral vaccine (H. influenzae, K. pneumoniae, S. pyogenes and S. pneumoniae) were observed in all samples. The numbers of SAFC were significantly higher in the subjects who had received the oral vaccine. These results support the efficiency or oral immunization in increasing local defenses, even at distance from the sensitized gut-associated lymphoid tissue. These data provide evidence for the homing phenomenon in human mucosae associated lymphoid tissue (MALT). PMID- 2184138 TI - Identification of the mononuclear cell infiltrate in the superior cervical ganglion of athymic nude and euthymic rats after guanethidine-induced sympathectomy. AB - Guanethidine sulphate 40 mg/kg intraperitoneally for 14 days induced chromatolysis and nerve cell death in the superior cervical ganglia of athymic nude (rnu/rnu) LEW/Mol rats and their euthymic (+/rnu) LEW/Mol heterozygous littermates. Histologically the sympathetic ganglia were dominated by an infiltration of small inflammatory cells. By means of monoclonal antibodies these cells were identified. The number of B-lymphocytes increased following guanethidine in both athymic and euthymic rats. The number of T-lymphocytes increased to a great extent in euthymic rats, but was virtually missing in athymic rats. The number of NK-cells and monocytes/macrophages increased in both athymic and euthymic rats. The conclusion is, that guanethidine exerts a direct effect on sympathetic ganglion cells followed by a thymus-independent immune response. PMID- 2184139 TI - Grenz ray therapy. PMID- 2184140 TI - The international origin of knowledge. Coincidence and reality. PMID- 2184141 TI - Cryptococcal cellulitis in congenital lymphedema. AB - A 27-year-old woman with intestinal lymphangiectasia and congenital lymphedema developed cryptococcal cellulitis as a result of her underlying depressed cell mediated immune responsiveness. Prompt therapy with amphotericin B and 5 fluorocytosine resulted in an excellent outcome. The authors believe that the increasing population of patients with depression of cell-mediated immune response will lead to an increase in the frequency with which cryptococcal cellulitis is seen and emphasize that proper evaluation of a patient with presumptive cellulitis includes consideration of fungal, as well as bacterial, etiology. PMID- 2184142 TI - "The Crazy Canucks". PMID- 2184143 TI - Lupus? Which lupus? PMID- 2184144 TI - Abnormal growth hormone responses to hypoglycemia and exercise in adults with type I diabetes. AB - Abnormal regulation of growth hormone (GH) secretion has been reported in some patients with insulin-dependent diabetes (IDD). We compared the GH responses in 32 healthy subjects (age 25 +/- 2 SE years) and in 23 IDD patients (28 +/- 1.9 years old, diabetes duration 10.4 +/- 2 years, and glycohemoglobin levels 9.3 +/- 2.0%). During acute, severe hypoglycemia (glucose less than 40 mg/dl), the mean GH levels were similar. When prolonged mild hypoglycemia was induced (58.0 +/- 2.0 mg/dl in the controls and 54.0 +/- 2.0 mg/dl in the IDD patients), the mean GH levels were similar, although the increase in GH was delayed in the latter group. During brief (30 min) exercise at 40-50% of VO2max, GH rose comparably in both groups (IDD patients maintained euglycemia with basal insulin infusion). However, with more prolonged and intense exercise using a glucose clamp to maintain euglycemia, GH rose to 5.4 +/- 2.2 ng/ml in controls and 26.4 +/- 12.6 ng/ml in the diabetics (P less than 0.05). When the combination of intense exercise and hypoglycemia (approximately 55 mg/dl) was used, GH rose to a peak of 21.7 +/- 2.7 ng/ml in the controls and to 33 +/- 3.0 ng/ml in the diabetics (P = NS). Our data show that in insulin-infused IDD patients made euglycemic for these experiments: a) The GH response to acute, severe hypoglycemia was identical to that in the controls and the response to mild, prolonged hypoglycemia was delayed, but of similar magnitude compared with controls; b) Exercise-induced GH responses were observed in both groups, but exaggerated in the diabetics at a higher exercise intensity; c) Hypoglycemia during exercise produced an additive effect on GH secretion in the controls but not in the IDD patients. We conclude that the wide range of abnormal GH secretory responses in type I diabetes reflects a central, possibly hypothalamic, defect in GH regulation. PMID- 2184145 TI - DNA fingerprinting. PMID- 2184146 TI - Ultrasonographic appearance of well-defined splenic space-occupying lesions in Gaucher's disease. PMID- 2184147 TI - The Quality Assessment Index (QAI) for measuring nursing home quality. AB - There have been few detailed evaluations of measures of quality of care in nursing homes. This is unfortunate because it has meant that much research on factors affecting nursing home quality has used measures of questionable reliability and validity. Moreover, some measures currently in use have been developed using methodologies not based on solid conceptual grounds, offering little reason to expect them to have much internal or external validity. In this article we suggest characteristics that should be present in measures of nursing home quality, propose a methodology for the development of such measures, propose a specific nursing home quality measure (the Quality Assessment Index or QAI), and report the results of several tests of its validity and reliability. PMID- 2184148 TI - Federal aid to dependent variables: surveying the health services research landscape. PMID- 2184149 TI - Operational efficiency research in Department of Veterans Affairs health services. PMID- 2184150 TI - Health Services Research and Development: a tool for hospital management. AB - Mr. Zamberlan is one of seven major executives in the Department of Veterans Affairs (VA) Veterans Health Services and Research Administration (VHS&RA), directing health care in a five-state region that includes 21 medical centers, 7 outpatient clinics, and 19 veterans outreach centers. As a medical center director in the 1970s, he was one of the earliest advocates for using health services research to support executive decision making and was the first medical center director selected to serve on the VA HSR&D Research Advisory Committee. In this editorial, Mr. Zamberlan outlines his perspective on HSR&D in VA and relates it to the activities of the HSR&D Field Program in the region he directs, which is based at the VA Medical Center in Ann Arbor, MI. PMID- 2184151 TI - The whole is greater than the sum of its parts: the anatomy of the Department of Veterans Affairs Medical District 17 Health Services Research and Development Field Program. AB - The Medical District 17 Health Services Research and Development (HSR&D) Field Program was funded by the Veterans Administration (now the Department of Veterans Affairs--VA) in January 1983. This article describes the organization, progress, and accomplishments of this field program, and it provides a review of the breadth of health services research that is being conducted in Medical District 17. Overall, the field program has conducted research that addresses significant problems in the delivery of health care within the VA system. Resource utilization, cost effectiveness, and the care of geriatric patients have been some of the areas in which the Medical District 17 HSR&D Field Program has provided important research findings for VA. The field program plans to continue its response to the needs of VA. Moreover, HSR&D investigators will be collaborating with researchers of other services to conduct research that is both enlightening and highly relevant to the delivery of health care to the nation's veterans. The proposal for an HSR&D field program was developed by the Edward A. Hines Jr. VA Hospital in collaboration with the Center for Health Services and Policy Research (CHSPR) of Northwestern University. The program was funded in January 1983, as the result of a national competition to establish an HSR&D field program in each of the VA regions. The goals of the Medical District 17 Field Program are to improve the health care of veterans by conducting relevant research on the processes and outcomes of patient care; to provide comprehensive technical research assistance; and to educate VA managers, planners, and clinicians, as well as the general medical community, about advances in health care delivery. The field program's commitment to excellence is strengthened by its multidisciplinary approach, which enables physicians, nurses, social workers, psychologists, sociologists, economists, statisticians, administrators, and individuals in various related disciplines to cooperate in efforts to address a wide range of topical issues. These collaborations are a major strength of the field program. Primary research priorities of the field program are cost effectiveness of VA services (e.g., patient care technologies, delivery systems), long-term care, and rehabilitation. Investigators, however, are not limited to these topics and explore many other health services research issues of particular interest to them. PMID- 2184153 TI - A brief glance back at 45 years in veterinary education. PMID- 2184152 TI - An immunohistochemical study of localization of type I and type II collagens in mandibular condylar cartilage compared with tibial growth plate. AB - Immunohistochemical localization of type I and type II collagens was examined in the rat mandibular condylar cartilage (as the secondary cartilage) and compared with that in the tibial growth plate (as the primary cartilage) using plastic embedded tissues. In the condylar cartilage, type I collagen was present not only in the extracellular matrix (ECM) of the fibrous, proliferative, and transitional cell layers, but also in the ECM of the maturative and hypertrophic cell layers. Type II collagen was present in the ECM of the maturative and hypertrophic cell layers. In the growth plate, type II collagen was present in the ECM of whole cartilaginous layers; type I collagen was not present in the cartilage but in the perichondrium and the bone matrices. These results indicate that differences exist in the components of the ECM between the primary and secondary cartilages. It is suggested that these two tissues differ in the developmental processes and/or in the reactions to their own local functional needs. PMID- 2184154 TI - Changes in accessory sex glands of stallions after sexual preparation and ejaculation. AB - Ultrasonographic images of the accessory sex glands of 8 stallions were recorded immediately prior to sexual preparation, immediately after sexual preparation, and immediately after ejaculation. Relative size changes, determined by measurements of ultrasonograms of accessory sex gland, were contrasted. Length and width of the bulbourethral glands increased significantly (P less than 0.05) after sexual preparation and decreased significantly (P less than 0.05) after ejaculation. The increase in bulbourethral gland volume following sexual preparation was correlated significantly (P less than 0.01) with the number of false mounts attempted by stallions during sexual preparation. Diameter of the pelvic portion of the urethra did not change significantly (P greater than 0.05) after sexual preparation or after ejaculation. Prostate gland lobular and isthmic thickness increased significantly (P less than 0.05) after sexual preparation and decreased significantly (P less than 0.05) after ejaculation. Total and lumenal diameter of the ampullae increased significantly (P less than 0.05) after sexual preparation and decreased significantly (P less than 0.05) after ejaculation. Diameter of the ampulla wall did not change significantly (P greater than 0.05) after sexual preparation or ejaculation. Reduction of the lumenal area of the ampullae after ejaculation was not correlated (P greater than 0.05) to concentration of spermatozoa or total spermatozoa per ejaculate. Total and lumenal diameters of the vesicular glands increased significantly (P less than 0.05) after sexual preparation and decreased significantly (P less than 0.05) after ejaculation. Diameter of the vesicular gland wall did not change significantly (P greater than 0.05) after sexual preparation or ejaculation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2184155 TI - Serratia marcescens mastitis in a dairy herd. AB - Serratia marcescens caused clinical mastitis in 5 cows and nonclinical mastitis in 21 cows of a 190-cow herd. Repeated bacteriologic culture of specimens from the cows, postmilking teat dip, environment, and equipment was performed. Serratia marcescens was not isolated from the dip, environment, or equipment. Progress of the infection in cows was monitored for 10 months. Some cows remained infected with S marcescens for at least 10 months. Economic loss estimates were based on Dairy Herd Improvement Association linear score reports. The average nonclinical loss was about $22/cow. PMID- 2184156 TI - Chronic osteomyelitis associated with orthopedic implants and cranial cruciate repair in three dogs. PMID- 2184157 TI - Antimicrobial agents in Lyme disease. PMID- 2184158 TI - Antimycotic effects of octenidine and pirtenidine. AB - The effects of octenidine and pirtenidine on yeasts (in particular Candida albicans) have been studied. MIC and MCC values have been established as well as the inhibitory effects on growth, budding and germ tube formation. The drugs were shown to cause extensive leakage of cytoplasmic contents from the cells which was correlated with morphological and ultrastructural changes in the yeast. PMID- 2184160 TI - The emergence and mechanisms of trimethoprim resistance in Escherichia coli isolated from outpatients in Finland. AB - Trimethoprim (TMP), either alone or in combination with sulphonamides, is commonly used for treating urinary tract infections. In Finland, TMP alone has been in clinical use since 1973. TMP resistance in the major outpatient urinary tract pathogen, Escherichia coli, increased during 1978-1988 from 5% to 16% in the Turku area, during 1980-1988 from 3% to 19% in the Helsinki area and also during 1980-1988 from 3% to 14% in the Rovaniemi area. The majority (91%) of TMP resistant strains were highly-resistant to TMP (MIC greater than or equal to 1024 mg/l). The most common (57%) TMP resistance gene, detected by DNA hybridization, was the type I dihydrofolate (DHFR) gene. The type II DHFR genes were found in less than 3% of the strains studied. No positive hybridizations were detected with the type III DHFR probe, and only a few positive hybridizations were found with the type V DHFR probe. Forty percent of the isolates did not hybridize with any of the DHFR probes used, suggesting additional unknown resistance mechanisms responsible for the high-level TMP resistance. These unknown TMP resistance mechanisms, together with the type I DHFR-mediated resistance, were responsible for the increase of TMP resistance among the E. coli strains studied. PMID- 2184159 TI - In-vivo evaluation of ofloxacin in Salmonella typhimurium infection in mice. AB - The effects of ofloxacin in Salmonella typhimurium infection in mice were compared with those of ciprofloxacin, ampicillin and chloramphenicol. Oral administration of ofloxacin at 10, 50 or 100 mg/kg once per day for seven days significantly (P less than 0.02) increased survival (20.1 days at 100 mg/kg) of infected mice relative to non-treated controls (4.1 days). In addition, after oral treatment with 100 mg/kg of each of the antibiotics, ofloxacin was significantly more effective than ampicillin (9.9 days), chloramphenicol (8.4 days) or ciprofloxacin (14.9 days) in prolonging the mean survival time of these mice. A comparison of oral potencies indicates that ofloxacin is five times more potent than ciprofloxacin (oral ED50 = 13.3 mg/kg vs ciprofloxacin = 69.9 mg/kg) and over eight times more potent than either of the other two antibiotics. When the number of bacteria from livers and spleens was quantitated, only ofloxacin (25 or 100 mg/kg,po) significantly (P less than 0.02) reduced the number of viable bacteria in both of these tissues in comparison with untreated controls, and, relative to the other antibiotics, ofloxacin (100 mg/kg) caused a significantly greater reduction. Single oral dosing of 20 mg/kg of either ofloxacin or ciprofloxacin showed that ofloxacin achieves approximately a four fold higher peak serum or liver concentration than ciprofloxacin, which may contribute to its better efficacy in this infection model. These results taken together suggest that oral ofloxacin may be of value in treating systemic salmonella infections in humans. PMID- 2184161 TI - Nitrofurantoin resistance in isolates of Salmonella enteritidis phage type 4 from poultry and humans. AB - All 38 isolates of Salmonella enteritidis phage type (PT) 4 from chickens and 86 of 89 isolates from human patients were resistant to nitrofurantoin. Resistance to other agents was rare. Thirteen of 16 isolates of S. enteritidis other than PT4 were nitrofurantoin-resistant, and resistance to other agents was slightly more common than with isolates of PT4. Only one third of 83 isolates of other salmonella serotypes were nitrofurantoin-resistant, but resistance to other agents was more common and some isolates were multiply resistant. There was generally cross-resistance between nitrofurantoin and furazolidone although there were discrepancies with isolates that had MICs close to the breakpoint. It may be that use of nitrofurans in the poultry industry has selected for colonization and infection with S. enteritidis PT4. This could explain the prevalence of the organism in poultry and in human enteric infection in the United Kingdom. PMID- 2184162 TI - Penetration of ceftazidime into intracranial abscess. PMID- 2184164 TI - Glucose deprivation neuronal injury in vitro is modified by withdrawal of extracellular glutamine. AB - Cultured cortical neurons deprived of glucose in a defined solution containing 2 mM glutamine became acutely swollen and went on to degenerate over the next day; this neuronal loss could be substantially attenuated by an N-methyl-D-aspartate (NMDA) antagonist. Removal of extracellular glutamine produced two effects: an increase in overall neuronal injury and a decrease in the protective effect of an NMDA antagonist. Both effects of glutamine removal were glutamine concentration dependent (EC50 for both approximately 300 microM) and not reversed by substitution of equimolar concentrations of alanine or arginine. These observations suggest that glucose deprivation neuronal injury may be tonically regulated by the presence of extracellular glutamine. We speculate that glutamine may reduce overall injury by serving as an energy substrate in the absence of glucose, but may increase NMDA receptor-mediated injury by serving as a precursor for transmitter excitatory amino acids. PMID- 2184163 TI - Evaluation of the annexins as potential mediators of membrane fusion in exocytosis. AB - Membrane fusion is a central event in the process of exocytosis. It occurs between secretory vesicle membranes and the plasma membrane and also among secretory vesicle membranes themselves during compound exocytosis. In many cells the fusion event is regulated by calcium. Since the relevant membranes do not undergo fusion in vitro when highly purified, much attention has been paid to possible protein mediators of these calcium-dependent fusion events. The annexins comprise a group of calcium-dependent membrane-aggregating proteins, of which synexin is the prototype, which can initiate contacts between secretory vesicle membranes which will then fuse if the membranes are further perturbed by the addition of exogenous free fatty acids. This review discusses the secretory pathway and the evidence obtained from in vitro studies that suggests the annexins may be mediators or regulators of membrane fusion in exocytosis. PMID- 2184165 TI - Human responses to transitions: a holistic nursing perspective. PMID- 2184166 TI - Transitions in chronic illness: the at-risk role. PMID- 2184167 TI - Transitions in midlife adults with long-term illness. PMID- 2184168 TI - Microenvironmental contributions to the chromatographic behavior of subtilisin in hydrophobic-interaction and reversed-phase chromatography. AB - Genetically engineered variants were used to examine how microenvironmental changes in the S1 substrate binding subsite of subtilisin contribute to chromatographic behavior of proteins on hydrophobic-interaction chromatography (HIC) and reversed-phase chromatography (RPC) columns. Gradient elution studies over a wide pH range showed that conditions could be found where a HIC support could separate proteins varying by one amino acid. Although all single-site variants could not be separated by HIC, this chromatographic mode was found to be complementary to cation-exchange chromatography for the separation of such variants. RPC was found to be of much less utility in the resolution of variant proteins. Retention and resolution of subtilisin variants was found to vary on RPC with the concentration and type of mobile phase pairing agent. PMID- 2184170 TI - [Studies on the mechanisms of action of disopyramide on insulin secretion. The modification by high glucose solution]. AB - Using the islet perifusion preparation and the isolated rat pancreas in situ perfusion preparation, the effects of disopyramide (Diso) on insulin secretion were studied. In an isolated pancreatic islet perifusion experiment, Diso (300 micrograms/ml) produced a significant increase in the immunoreactive insulin (IRI) level in the perfusate. The Diso-induced IRI rise was not affected by pretreatment with various autonomic blocking agents, such as propranolol, phentolamine or atropine. In an isolated rat pancreas in situ perfusion experiment, the IRI level in the perfusate increased significantly after the administration of Diso (300 micrograms/0.1 ml) under the perfusion of Krebs Ringer bicarbonate buffer solution containing 0.3% glucose (0.3% glucose buffer), but not under the perfusion of Krebs-Ringer bicarbonate buffer solution containing 0.1% glucose (0.1% glucose buffer). The Diso-induced IRI rise was not affected by pretreatment with the autonomic blocking agents. Diso suppressed the IRI rise which was induced by additional glucose application (25%, 0.2 ml) under the perfusion of 0.1% glucose buffer, but not under the perfusion of 0.3% glucose buffer. Furthermore, Diso also suppressed the hypersecretion of insulin induced by increasing the glucose concentration from 0.1% to 0.3% in the perfusion fluid. The suppressing action of Diso on glucose-stimulated insulin secretion was partially recovered after pretreatment with propranolol or phentolamine. These findings show that Diso has both stimulatory and inhibitory effects on insulin secretion processes, and that the inhibitory action of Diso is suppressed by high glucose solution. PMID- 2184169 TI - Column liquid chromatography of endotoxins. AB - A new, fast and highly reproducible column liquid chromatographic method was elaborated for the analysis and small-scale preparative isolation of endotoxin from Serratia marcescens Bizio (ATCC No. 264). This procedure detects contaminants of such preparations with high sensitivity and it is capable of separating them from endotoxic components. Extensive heterogeneity of both 5% trichloroacetic acid and phenol-water-extracted endotoxin preparations was recorded. Heterogeneity among the endotoxic components of purified preparations could also be detected by this method. Measurements of biological activities, such as Limulus amoebocyte lysate activation, lymphoblastogenesis (mitogenicity) and tumor necrosis factor (TNF) liberation were carried out on the chromatographically separated fractions. During these studies, non-toxic but in vitro TNF-generating components of crude endotoxin extracts were also detected. PMID- 2184171 TI - Communication disorder in renaissance Italy: an unreported case analysis by Hieronymus Mercurialis (1530-1606). AB - This paper presents and explains an early clinical discussion of the case of a young nobleman who had developed a severe speech impediment associated with anxiety. The discussion was written by the famous Italian physician Hieronymus Mercurialis, in consultation with the renowned surgeon Gaspar Tagliacozzi, probably in the late 1580s. The case had first come to the attention of Dr. Pio Enea Caprili, who wrote to Mercurialis for an opinion. It has not heretofore been cited in the modern literature on communication disorders. The document is placed in its intellectual context and modern analogues are cited. Mercurialis' discussion belongs to a highly developed tradition of language study in medicine and natural philosophy that goes back to ancient Greece and deserves to be better known. A brief survey of late 16th century literature on voice and speech is provided in an appendix. PMID- 2184172 TI - Lipids of bovine and human milks: a comparison. AB - Human and bovine milks contain about 3 to 5% total lipid, existing as emulsified globules 2 to 4 microns in diameter and coated with a membrane derived from the secreting cell. About 98% or more of the lipid is triacylglycerol, which is found in the globule. Phospholipids are about .5 to 1% of total lipids and sterols are .2 to .5%; these are mostly located in the globule membrane. Cholesterol is the major sterol. The major differences are in fatty acid composition, triacylglycerol structure, and the response of fatty acids in human milk to changes in diet. Bovine milk contains substantial quantities of 4:0 to 10:0, about 2% 18:2, and almost no other long-chain polyunsaturated fatty acids. The fatty acid composition is not altered by ordinary changes in diet. Human milk contains very little 4:0 to 10:0, 10 to 14% 18:2, and small quantities of other polyunsaturates. The triacylglycerol structure differs, with much of the sn-2 position occupied by 16:0 in human milk and 4:0 to 10:0 at sn-3 in bovine milk. The effects of milk cholesterol and fatty acids on human blood cholesterol levels are discussed. PMID- 2184173 TI - Effect of severity of systemic signs during the acute phase of experimentally induced Escherichia coli mastitis on milk production losses. AB - The objectives were to describe the systemic signs during the acute phase of experimental Escherichia coli mastitis and to relate these with losses in milk production during the reconvalescent period. Eleven cows, 20 to 30 d postpartum, were inoculated with 10(4) cfu of E. coli O157 in rear quarters. Heart rate, rectal temperature, frequency and amplitude of rumen contractions, plasma Zn and Fe concentrations, and counts of E. coli were used to monitor severity of disease during the acute phase. Areas under curves of clinical parameters, plasma Zn and Fe concentrations, and counts of E. coli were calculated during 36, 120, and 125 h postinoculation, respectively. Areas under curves of milk production were calculated during 21 d postinoculation. Losses in total daily milk production were related positively with areas under curves of heart rate, rumen amplitude, counts of E. coli in secreta from inoculated quarters, and plasma Zn and Fe concentrations. These parameters may prove suitable to establish an accurate prognosis for returning to milk production cows suffering from acute or peracute E. coli mastitis and to evaluate efficacy of drugs in experimental mastitis. PMID- 2184174 TI - Preinfection functions of blood polymorphonuclear leukocytes and the outcome of experimental Escherichia coli mastitis in the cow. AB - The relationship between preinfection functions of blood neutrophils and outcome of experimental Escherichia coli mastitis was studied in 11 cows. Random migration, chemotaxis, phagocytosis, and chemiluminescence by neutrophils were determined in white blood cell suspensions, and in purified neutrophil suspensions. The course of E. coli mastitis (10(4) E. coli 0:157 in rear quarters) was monitored using clinical parameters, counts of E. coli in mastitic secretion, and milk production. Regressions were calculated for areas under curves of these parameters and preinfection activities of neutrophils. Chemiluminescence by nonstimulated neutrophils in white blood cell suspensions was negatively correlated with counts of E. coli in secretion and with losses in milk production. The chemotactic differential in white blood cell suspensions minus the chemotactic differential in purified suspensions of neutrophils referred to as delta varied from -.66 to +.50, indicating, respectively, inhibition and stimulation of chemotactic activity of neutrophils in white blood cell suspensions. Delta correlated negatively with counts of E. coli in mastitis secretion, inhibition of the amplitude of rumen contractions, and losses in milk production. We hypothesize that a factor in white blood cell suspensions may be involved in the down-regulation of the migratory response of neutrophils during E. coli mastitis. PMID- 2184175 TI - Growth of gram-negative bacteria in dry cow secretion. AB - Gram-negative bacteria (n = 192) isolated from infected bovine mammary glands were tested for growth in a pooled source of dry cow secretion. Growth of Klebsiella pneumoniae in dry cow secretion was greater than growth of Escherichia coli and Klebsiella oxytoca. Escherichia coli originating during the early dry period exhibited greater growth in dry cow secretion than those originating around calving or during lactation. Klebsiella pneumoniae growth did not differ with time of origin of intramammary infection. Escherichia coli, K. oxytoca, and K. pneumoniae growth in a synthetic medium was reduced by apolactoferrin plus Ig. Growth reduction was greatest for E. coli. Citrate reversed growth inhibition. The inhibitory properties of dry cow secretion for E. coli may contribute to the low number of naturally occurring intramammary infections originating during the early part of the dry period. Inhibitory properties of dry cow secretion are partially explained by lactoferrin acting in conjunction with antibody to prevent iron acquisition by many gram-negative bacteria. PMID- 2184176 TI - Effect of postmilking teat antisepsis on teat canal infections in lactating dairy cows. AB - Effects of a .18% iodophor teat dip and a fatty acid plus lactic acid teat dip on teat canal infections were studied in two separate trials under experimental challenge procedures using Staphylococcus aureus and Streptococcus agalactiae. The iodophor teat dip was 90% effective in preventing new S. aureus teat canal infections and 95.6% effective in reducing progression of S. aureus teat canal infections to intramammary infections. The dip also reduced persistence of S. aureus teat canal colonizations from week to week by 94.4%. The fatty acid plus lactic acid dip had no effect on preventing S. aureus teat canal infections but reduced progression of S. aureus teat canal infections to intramammary infections by 43.8%. The fatty acid plus lactic acid dip also reduced the persistence of S. aureus teat canal infections by 39%. An insufficient number of Strep. agalactiae teat canal infections was detected in both trials for valid analyses. Neither dip had any effect on prevalence of naturally occurring, coagulase-negative staphylococcal teat canal infections or on teat canal infections by other organisms. PMID- 2184177 TI - A case of tick bite with Ixodes turdus Nakatsuji--a report from Japan. AB - The first case of tick bite by Ixodes turdus Nakatsuji was reported. The tick was found on the occipital area near the left ear of a 6-year-old boy. The tick bite occurred in Hoya, a suburb of Tokyo. PMID- 2184178 TI - Connective tissue diseases in the skin--from molecules to symptoms. PMID- 2184179 TI - Topical PUVA, etretinate, and combined PUVA and etretinate for palmoplantar pustulosis: comparison of therapeutic efficacy and the influences of tonsillar and dental focal infections. AB - Twenty patients with palmoplantar pustulosis (PPP) were treated with topical PUVA, oral etretinate (Re), or combined PUVA and etretinate (Re-PUVA). Re and Re PUVA treated sites improved and/or cleared more rapidly than PUVA treated sites. Complete clearance was observed in six of ten sites treated with Re-PUVA, two of ten with Re, and one of ten sites with PUVA within 12 weeks. UVA-control sites failed to be cleared within 12 weeks. Remission periods after stopping the treatment were 1.5 +/- 0.5 weeks (n = 2) with Re, 10.5 +/- 11.4 weeks (n = 6) with Re-PUVA, and one year (n = 1) with PUVA. These results overall suggested that Re-PUVA is the most effective treatment for PPP. Tonsillar focal infection (TFI) and dental focal infection (DFI) were found in 6/20 and 17/20 patients, respectively. However, the presence of focal infection (FI), TFI and/or DFI, did not appear to interfere with the therapeutic activities of Re and/or PUVA, because the complete clearance rates and remission periods in FI(+) patients were comparable with those in FI(-) patients. PMID- 2184180 TI - The prognostic significance of first myocardial infarction type (Q wave versus non-Q wave) and Q wave location. The Multicenter Diltiazem Post-Infarction Research Group. AB - The prognostic significance of the type of first acute myocardial infarction (Q wave versus non-Q wave) and Q wave location (anterior versus inferoposterior) was determined from a multicenter data base involving 777 placebo-treated patients who were participants in the Multicenter Diltiazem Post-Infarction Trial. There were 224 patients (29%) with a non-Q wave infarction, 326 (42%) with an inferoposterior Q wave infarction and 227 (29%) with an anterior Q wave infarction. Mean left ventricular ejection fraction was significantly (p less than 0.001) lower in patients with an anterior Q wave infarction than in the other two groups (anterior Q wave 0.39; inferior Q wave 0.52; non-Q wave 0.53). Nevertheless, the total cardiac mortality rate during the follow-up period (average 25 months per patient) was only marginally higher (p = 0.42) in the anterior Q wave group (8.4%) than in the other two groups (inferoposterior Q wave 7.1%; non-Q wave 6.3%). The total first recurrent cardiac event was somewhat higher (p = 0.08) in the anterior Q wave group (18.1%) than in the other two groups (inferoposterior Q wave 11.7%; non-Q wave 15.6%). Survivorship analyses extending over 3 years revealed that electrocardiographic classification of the type of first infarction and Q wave location did not make significant independent contributions to the risk of postinfarction cardiac death or first recurrent cardiac event, either before or after adjustment for baseline clinical variables. PMID- 2184181 TI - Acute myocardial infarction: does the lack of Q waves help or hinder? PMID- 2184182 TI - The M-Heart percutaneous balloon mitral Valvuloplasty Registry: initial results and early follow-up. The M-Heart Group. AB - The initial results, complications and early follow-up of 74 patients undergoing percutaneous balloon mitral valvuloplasty in seven hospitals participating in a multicenter registry are reported. Seventy-four patients with a mean age of 53 years had 75 valvuloplasty procedures performed over a 2.5 year period. Eighty nine percent of the attempted procedures were completed and resulted in an increase in mean mitral valve area from 1.0 +/- 0.04 to 2.0 +/- 0.1 cm2 (p less than 0.0001); the valve area increased greater than or equal to 50% of the baseline valve area in 73% of the patients. Major complications included procedure-related death (2.7%), cardiac tamponade (6.7%), systemic embolism (2.7%) and emergency surgery (6.7%). At a mean follow-up period of 14.6 months, the condition of the majority of patients had improved, and 89% of 55 patients treated only with valvuloplasty were in New York Heart Association functional class I or II. Thus, hemodynamic and clinical improvement can be obtained in the majority of patients with mitral stenosis treated with balloon valvuloplasty in multiple centers. However, suboptimal results and major complications occurred in a significant number of patients and may limit this procedure to use by experienced operators in hospitals with facilities for cardiac surgery. PMID- 2184183 TI - Infective endocarditis, 1983-1988: echocardiographic findings and factors influencing morbidity and mortality. AB - The echocardiograms and clinical records of 70 patients with infective endocarditis seen between 1983 and 1988 were examined to evaluate the role of two dimensional and Doppler echocardiography in the diagnosis of infective endocarditis and identify risk factors for morbidity and mortality. A blinded observer reviewed the echocardiograms for the presence and size of vegetations and the severity of the valvular regurgitation. Vegetations were identified in 54 (78%) of 69 technically satisfactory echocardiograms. In 38 patients whose heart was examined at surgery or autopsy, all vegetations diagnosed by echocardiography were confirmed, but six additional vegetations were found. Abnormal (greater than or equal to 2+) valvular regurgitation was present in 88% of patients. No patient with less than or equal to 1+ regurgitation (n = 8) died or required valve surgery for heart failure, but three of the eight patients did undergo surgery for mycotic aneurysm, recurrent embolism or paravalvular abscess. In patients without embolism before echocardiography, there was a trend toward a greater incidence of subsequent embolism in those with vegetations greater than 10 mm in size (26% [8 of 31] compared with 11% [2 of 18] with vegetations less than or equal to 10 mm) (p = 0.19). By multivariate analysis, risk factors for in hospital death (n = 7) were an infected prosthetic valve (p less than 0.007), systemic embolism (p less than 0.02) and infection with Staphylococcus aureus (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2184184 TI - Quantification of aortic regurgitation with amplitude-weighted mean flow velocity from continuous wave Doppler spectra. AB - Aortic regurgitant fraction (RFao) was quantified by estimating the ratio of the forward blood flow through the aortic (Qao) and pulmonary (Qp) valve: RFao = 100(Qao - Qp)/Qao. Aortic and pulmonary flow were measured by the systolic time integrals of the amplitude-weighted mean velocity from continuous wave Doppler spectra recorded over the aortic and pulmonary valves. Thus, measurements are independent of the left and right ventricular outflow tract area. In 20 normal subjects, aortic regurgitant fraction ranged between -2.9% and +12.0% (mean +4.3%), the physiologic value being +2%. In 20 patients with pure aortic regurgitation, aortic regurgitant fraction obtained by Doppler spectra (y) was compared with that calculated from biplane left ventriculography and cardiac output determined with the Fick method (x). The correlation was r = 0.94, (SEE = 5.4%, which is 10.6% of the angiography-Fick mean value). The regression line was y = 0.87x + 6.6 (mean y = 51.2%, mean x = 51.1%). It is concluded that determination of aortic regurgitant fraction in pure aortic regurgitation by using the amplitude-weighted mean velocity from continuous wave Doppler spectra is accurate and allows easy noninvasive evaluation of the regurgitant fraction in routine clinical applications. PMID- 2184185 TI - Catheter-based intravascular ultrasound discriminates bicuspid from tricuspid valves in adults with calcific aortic stenosis. AB - A catheter-based intravascular ultrasound transducer was used to study aortic valve morphology in adults with calcific aortic stenosis. Examination of 14 postmortem specimens disclosed that intravascular ultrasound consistently identified the number of cusps or the presence of a calcified median raphe in the conjoined cusp, or both, and thereby distinguished a calcified bicuspid from a calcified tricuspid aortic valve. These postmortem findings were then employed to identify valvular morphology in 15 patients undergoing diagnostic cardiac catheterization or balloon aortic valvuloplasty, or both. Reproduction of criteria established in vitro allowed discrimination of congenital valvular morphology in all 15 patients, including 7 in whom assessment by intravascular ultrasound was confirmed by subsequent pathologic examination. Identification of aortic valvular morphology by intravascular ultrasound has potential therapeutic implications for patients considered to be candidates for operative or nonoperative aortic valvuloplasty. PMID- 2184186 TI - A randomized trial of family caregiver support in the home management of dementia. AB - A randomized trial of family caregiver support for the home management of older people suffering from moderate to severe progressive irreversible dementia was conducted in an urban center in southern Ontario. Thirty caregivers were allocated to receive the experimental intervention consisting of: caregiver focused health care, education about dementia and caregiving, assistance with problem solving, regularly scheduled in-home respite, and a self-help family caregiver support group. Thirty control subjects received conventional community nursing care. Before completion of the intervention, 18 (30%) were withdrawn, almost equally from each group. The most frequent reason was long-term institutionalization of the demented relative (n = 10). At baseline, caregivers in both groups were suffering from above-average levels of depression and anxiety. After the six-month intervention period, we found neither experimental nor control group improved in these areas. However, the experimental group showed a clinically important improvement in quality of life, experienced a slightly longer mean time to long-term institutionalization, found the caregiver role less problematic, and had greater satisfaction with nursing care than the control group. PMID- 2184187 TI - The Senior Care Study. Does inpatient interdisciplinary geriatric assessment help the family caregivers of acutely ill older patients? AB - Comprehensive geriatric assessment has emerged as an effective strategy for improving outcomes for frail older patients in the hospital setting. Attention, however, has not been given to determining whether this process has any effect on their family caregivers. As part of a randomized controlled clinical trial designed to test the efficacy of early interdisciplinary geriatric assessment for acutely ill hospitalized patients 75 years of age or older, their family caregivers were studied to determine if the process had a positive effect on caregivers' self-reported health and emotional well-being. One hundred forty-two caregivers were approximately evenly distributed between experimentals (n = 69) and controls (n = 73). By three months after the patients' hospitalization, experimental caregivers were more likely to report good general health (81% vs 63%, P = .049) than were controls. The positive effect persisted after statistical adjustment for confounding variables. Experimental caregivers were not significantly more likely to have good emotional health at follow-up than were controls (65% vs 58%, P = .43), even after statistical adjustment. Although the findings are modest, they suggest that the acute hospital setting may be an ideal place to develop interventions designed to enhance family caregivers' well being during the early months following hospitalization. This may be particularly true when the interventions with caregivers are coupled with a geriatric assessment and care plan process. PMID- 2184188 TI - The aging-disease dichotomy. Cerebral amyloid angiopathy--an independent entity associated with dementia. PMID- 2184189 TI - Contribution of thyroid ultrasound and serum calcitonin to the diagnosis of congenital hypothyroidism. AB - To elucidate the role of thyroid ultrasound (TU) in the diagnosis of congenital hypothyroidism (CH), we compared 1) TU and thyroid scintigraphy (TS) in 6 CH newborns and 2) TU results in the 6 CH newborns, in 8 newborns with "false positive" results at screening, in 13 CH children aged 2 mo to 12 yr treated since the neonatal period and in 235 controls aged 0-12 yr. RESULTS: 1) In all 6 CH newborns with no thyroid uptake at TS, TU evidenced small posterior hyperechogenic masses in the thyroid area [Vol: 322 +/- 180 (SD) mm3]; 2) In all normal controls and in the 8 "false positive" cases at screening TU showed normal thyroid structures. The thyroid volume was 831 +/- 383 mm3 in normal newborns and progressively increased with age. In the older CH children, TU also demonstrated the hyperechogenic masses, but their volume barely increased with age: as a consequence, the difference between the volume of the masses in CH patients and the thyroid tissue in controls, already significant in newborns (p less than 0.01), markedly increased with age. The exact nature of these masses is unknown; they could represent poorly vascularized ultimobranchial remnants containing the calcitonin - secreting cells: this hypothesis is supported by our finding that serum concentrations of calcitonin (measured by a sensitive extraction method) (mean +/- SD, pg/ml) were lower in the CH patients (2.9 +/- 1.5) than in controls (13.0 +/- 6.9; p less than 0.001) at birth. In conclusion, in all cases of CH, TU showed abnormal structures in the thyroid area. TU and TS provide complementary information in the diagnosis of CH, and TU should be routinely performed in all newborns suspected of CH to avoid unnecessary use of TS in unaffected infants. PMID- 2184190 TI - Neuroendocrine-thymus interactions. I. In vitro modulation of thymic factor secretion by thyroid hormones. AB - Several in vivo experimental and clinical studies suggest that the production of thymic hormones, such as thymulin (Zn-FTS), is modulated by thyroid hormones. It was not determined in these studies, however whether such modulation is exerted directly on the thymic epithelial cells which synthesize and secrete thymic hormones. In order to discriminate between direct and indirect modulation, the effect of thyroid hormones on the in vitro production of thymulin by whole thymic organ culture, as detected by the rosette inhibition assay, has been investigated. Donors of thymuses were young 6N-propyl-2 thiouracil (PTU)-treated hypothyroid Balb/c mice and normal littermates. Thymuses from hypothyroid mice were shown to produce concentrations in vitro nearly undetectable of thymic hormone, when compared to thymuses from normal mice. The in vitro addition of triiodothyronine (T3) caused a complete recovery of the thymic hormone production by thymuses from hypothyroid mice and an increased synthesis even by normal thymuses over control values. The complete blockade of in vitro thymic hormone production with cycloheximide, which inhibits mRNA and protein synthesis but not thyroid hormone permissive actions, suggests that the T3 induced increment of thymic hormone level in the supernatant is due to de novo synthesis. Furthermore, the number of thymulin-producing cells, as detected by immunofluorescence using a specific antithymulin monoclonal antibody, which is quite low in thymuses from hypothyroid mice, is completely regained after in vitro incubation with T3. These findings support the idea that the modulation of thyroid hormones on thymic endocrine activity is directly exerted at thymic level. PMID- 2184191 TI - Granulocyte-macrophage colony-stimulating factor enhances cationic antimicrobial protein synthesis by human neutrophils. AB - We analyzed the effect of recombinant human granulocyte macrophage CSF (GM-CSF) on protein synthesis in peripheral blood polymorphonuclear leukocytes. GM-CSF enhanced PMN 35S-methionine incorporation 1.5-fold over a 2-h incubation period. The effect of GM-CSF on the synthesis of specific proteins was investigated by separating the radiolabeled proteins on SDS-PAGE followed by autoradiography. Stimulation of protein synthesis by GM-CSF was rapid (2 h), dose dependent, and affected at least 10 separate polypeptides. Using ion exchange chromatography some of the GM-CSF-enhanced proteins were identified to have a cationic nature, including the 37- and the 57-kDA proteins whose synthesis was increased by GM-CSF 2.4-fold and 1.6-fold, respectively. The cationic protein fractions from GM-CSF primed and control cells were eluted from an ion exchange column and tested for their antimicrobial activity. An overall twofold increase in the amount of cationic proteins was recovered from GM-CSF-treated cells as compared to control cells, and these proteins showed a proportional enhanced killing of S. typhimurium. These results suggest that enhanced cationic protein synthesis is an important mechanism whereby GM-CSF can increase neutrophil microbicidal activity via nonoxidative pathways. PMID- 2184192 TI - Decreased steady state c-myc mRNA in activated T cell cultures from old humans is caused by a smaller proportion of T cells that transcribe the c-myc gene. AB - The proliferative response of T cells is known to decrease with age of the T cell donor. We now report that this proliferative defect affects both major subsets (CD4+, CD8- and CD4-, CD8+) of peripheral T cells from old humans. Furthermore, this proliferative defect can be detected within the first hours after addition of mitogen by a reduction in the steady state levels of c-myc mRNA in T cell cultures from old donors. Lymphocytes from old humans cultured with PHA have less than 50% of the level of c-myc message than do such cultures from young donors. Nuclear run-on assays suggest that the decreased steady state level of c-myc mRNA in cultures from old donors is caused by reduced transcription of the c-myc gene in T cells from old donors. The age-associated defect in transcription of the c myc gene affects the second exon to a greater extent than the first, noncoding exon. Individual T lymphocytes from old donors that do express c-myc message, detected by in situ hybridization, have the same intracellular level of c-myc message as T lymphocytes from young donors. These data add additional support for the hypothesis that the proliferative defect of T lymphocytes from old humans is caused by the smaller fraction of T cells from old as compared with young humans that can be activated by mitogens to enter the G1 phase of the cell cycle. PMID- 2184193 TI - Deregulated Bcl-2 gene expression selectively prolongs survival of growth factor deprived hemopoietic cell lines. AB - The t(14;18) of human follicular B cell lymphoma translocates the Bcl-2 gene into the Ig H chain locus and markedly deregulates Bcl-2 expression. We sought to determine if Bcl-2 could be directly implicated in a growth-factor pathway. Consequently, we introduced a retrovirus containing the murine Bcl-2 gene (N2-M Bcl-2) or the parental retrovirus (N2) into a series of factor-dependent hemopoietic cell lines. Overexpressed Bcl-2 resulted in no long term IL-2, IL-3, or IL-6 independent clones, indicating that Bcl-2 could not spare the need for a specific ligand-receptor interaction. However, Bcl-2 did extend the short term survival of IL-3-dependent cell lines after factor deprivation. Although viable, IL-3-deprived pro B lymphocytes (FL5.12) bearing N2-M-Bcl-2 were in Go, and deregulated Bcl-2 did not obviously influence cell-cycle progression. Bcl-2 predominant effects were to delay the onset of cell death and to modestly augment viable cell growth in the first 48 h after IL-3 deprivation. This death sparing was associated with increased levels of Bcl-2 RNA and protein in factor-deprived cells possessing N2-M-Bcl-2. This result was not restricted to prolymphocytes because an IL-3-dependent mast cell line (32D) as well as a promyeloid line (FDC P1) demonstrated the same response to Bcl-2. Moreover, the effect was not limited to the IL-3/IL-3R signal transduction pathway in that promyeloid cells maintained in granulocyte-macrophage-CSF or IL-4 displayed a similar response. Yet, Bcl-2 enhanced cell survival was not universal as an IL-2-dependent T cell line, and an IL-6-dependent myeloma line demonstrated no consistent effect upon IL withdrawal. Thus, Bcl-2 appears to interfere with cell death but in a cell type and/or factor restricted fashion. PMID- 2184194 TI - Macro enzymes: prevalence, composition, detection and clinical relevance. AB - The presence of a macro enzyme, i.e. an enzyme with an abnormally high molecular weight, frequently leads to a genuinely increased serum activity or an interference in laboratory assays. This may thereby result in false positive diagnoses, such as acute myocardial infarction or pancreatitis. The various forms of macro enzymes are reviewed. In the case of immune complexes the immunoglobulins and (iso)-enzymes involved are discussed, as well as the specificity of the interaction, the prevalence and clinical relevance, associations with autoimmune or other diseases, and their behaviour in laboratory assays. PMID- 2184195 TI - Alveolar cell pattern and chemiluminescence response of blood neutrophils and alveolar macrophages in sheep after endotoxin injection. AB - In order to study the pathomechanisms of the Adult Respiratory Distress Syndrome in an acute animal model, we monitored the alveolar cell pattern and the stimulatory chemiluminescence responses of blood neutrophils and alveolar macrophages in sheep after Escherichia coli endotoxin injection (2 micrograms/kg of body weight). Using appropriate bronchoalveolar lavage techniques, thereby avoiding local inflammation, it was demonstrated that endotoxin injection did not cause any recruitment of neutrophils into the alveoli for a period of up to 24 hours. Following endotoxin injection, blood neutrophils showed a maximal stimulatory response after 5 minutes, and alveolar macrophages after 4 hours. It is concluded that if neutrophils are responsible for initiating the increase in microvascular permeability, then this action must be purely intravascular. PMID- 2184196 TI - Human chorionic gonadotropin detection by means of enzyme immunoassay: a useful method in forensic pregnancy diagnosis in bloodstains. AB - This paper reports on human chorionic gonadotropin (HCG) detection in bloodstains using a commercial kit based on enzyme immunoassay. The specificity and sensitivity of the method is tested, as well as HCG stability over time in the samples. Detection of this hormone in bloodstains is of special interest for pregnancy diagnosis in forensic science applications. The experimental series comprises 60 bloodstains prepared in our laboratory and obtained from blood samples taken from 30 pregnant women and 30 healthy, nonpregnant individuals. The bloodstains were studied at different stages of aging over a 6-month period, each sample being stored at 2 different temperatures throughout the process. The experimental evidence proves HCG to be a useful and stable diagnostic indicator of pregnancy in bloodstains. In addition, the technique used is fast, as well as highly sensitive and specific. PMID- 2184197 TI - Pathophysiology of congestive heart failure. AB - Although the mortality rate for cardiovascular disease is declining, the incidence of congestive heart failure (CHF) is escalating. This article reviews normal cardiovascular physiology and cellular anatomy; defines CHF; explores the etiologies, pathophysiology and clinical presentation of CHF; and briefly discusses diagnostic modalities and prognostic indices. PMID- 2184198 TI - Drug therapy of heart failure. AB - While the incidence of cardiovascular disorders has decreased over the past 10 to 20 years, the incidence of congestive heart failure (CHF) has more than tripled. Although much has been learned about the pathophysiology of CHF, the annual mortality rate continues to be high and the impact of medical management is still less than optimal. The goals of therapy are to minimize or eliminate any underlying causes, reduce sodium and water retention, reduce the workload of the heart, and increase contractility. This article reviews the rationale for and clinical use of diuretics, vasodilators, and inotropes in the management of CHF. PMID- 2184199 TI - Congestive heart failure: a review of nonpharmacologic therapies. AB - Although pharmacologic therapy is the mainstay of treatment for patients with congestive heart failure (CHF), several nonpharmacologic interventions are useful adjuncts in the overall management of this clinical syndrome. Comprehensive treatment plans include sodium and fluid restriction, as well as a balance of rest and physical activity. Hemofiltration and peritoneal dialysis may be effective in patients who have become resistant to diuretic therapy. Mechanical support from intraaortic balloon counterpulsation and ventricular assist devices has improved survival in certain high-risk patients. For patients refractory to conventional therapies, cardiac transplantation offers new hope. These interventions and the nursing care of patients with CHF are discussed in this article. PMID- 2184200 TI - The cardiovascular response to exercise in the patient with congestive heart failure. AB - Individuals with moderate to severe heart failure may benefit from cardiac fitness training. However, before recommending cardiac rehabilitation to this patient population, nurses must understand exercise physiology and the effects of exercise in the individual with chronic left ventricular dysfunction (LVD). Normal cellular response to exercise, normal cardiovascular responses associated with exercise, cardiovascular adaptation to exercise training or conditioning, cardiovascular responses to exercise in patients with LVD, and cardiac rehabilitation of the patient with chronic congestive heart failure are addressed in this article. Responses to isotonic exercise, rather than isometric, are emphasized. PMID- 2184201 TI - A framework for developing staff competencies. AB - Nursing science is progressing at such a rapid rate that it is difficult for nursing professionals to remain current with the knowledge and skills necessary to provide quality patient care. To assure that staff members demonstrate the required competencies, a framework composed of eight steps and a master plan for implementation is presented in this article. The framework offers staff development educators structure and direction in planning and conducting educational programs to achieve the goal of competency development. PMID- 2184202 TI - A competency-based model for nurse internships. PMID- 2184203 TI - Nodular mass in the anterior floor of the mouth. PMID- 2184204 TI - Central mucoepidermoid carcinoma of the jaw with distant metastasis: a case report and review of the literature. PMID- 2184205 TI - Periosteal osteosarcoma of the maxilla: a case report and review of literature. AB - Juxtacortical osteosarcomas, including periosteal and parosteal subtypes, are uncommon neoplasms of the jaws. In long bones, the biologic behavior of the periosteal variant is reported to be more aggressive than the parosteal tumor. Juxtacortical osteosarcoma of the jaws appears to have a slightly more favorable prognosis than in long bones, although a larger series of cases needs to be evaluated before a definitive conclusion concerning the behavior of juxtacortical osteosarcoma of the jaws can be made. PMID- 2184206 TI - Technique to assure proper intraoral wound edge alignment. PMID- 2184207 TI - Remarks in honor of Clark Darwin West, MD, in appreciation of his inspirational service to the Children's Hospital Medical Center, Cincinnati, Ohio. PMID- 2184208 TI - Festschrift in honor of Clark D. West, MD. PMID- 2184209 TI - Role of IgA in IgA nephropathy. AB - IgA nephropathy (Berger disease) is defined by the dominant or codominant deposition of IgA in the renal mesangium. There is much evidence in vitro to suggest up-regulation of the IgA immune response in patients. Data from tonsillar and bone marrow-derived lymphocytes and from in vivo immunization studies indicate that the primary defect is an up-regulated systemic one, rather than mucosal IgA production. Several lines of evidence suggest that increased IgA production alone is inadequate to explain the pathogenesis of Berger disease. Murine models of IgA nephropathy indicate that local complement activation mediated by deposited IgG is essential for mesangial cell proliferation and subsequent renal injury. Circulating immune complexes from patients with Berger disease contain IgA and IgG within the same lattice. In vitro studies of model immune aggregates containing various mixtures of IgA and IgG indicate that the IgG is the site of complement activation and fixation. The IgA in the aggregate actually inhibits both complement activation and binding to erythrocyte complement receptor CR1. This effect of IgA may prevent effective immune complex clearance. In future studies, more emphasis should be placed on the roles of IgG and complement in the pathogenesis of IgA nephropathy. PMID- 2184210 TI - Molecular pathophysiology of bacterial meningitis: current concepts and therapeutic implications. PMID- 2184211 TI - Prevalence and consequences of nocturnal hypoglycemia among conventionally treated children with diabetes mellitus. AB - To determine the prevalence and predictors of, and the glucose responses after, nocturnal hypoglycemia, we studied 135 pediatric patients with insulin-dependent diabetes mellitus on 388 nights. The frequencies of blood glucose values less than 60, 50, and 40 mg/dl (3.3, 2.8, and 2.2 mmol/L) at 2 AM were 14.4%, 7.0%, and 2.1%, and at 6 AM were 6.7%, 2.6%, and 0.5%, respectively. Longer duration of diabetes, higher daily insulin doses, and lower glycosylated hemoglobin values were all significant but weak predictors of 2 AM hypoglycemia (glucose less than or equal to 60 mg/dl (less than or equal to 3.3 mmol/L). A 10 PM glucose concentration less than or equal to 100 mg/dl (less than or equal to 5.6 mmol/L) was present on 48% of nights with 2 AM glucose values less than or equal to 60 mg/dl (less than or equal to 3.3 mmol/L), but only 24% of nights with 10 PM blood glucose values less than or equal to 100 mg/dl (less than or equal to 5.6 mmol/L) were followed by 2 AM hypoglycemia. After treatment of 70 episodes of 2 AM glucose concentrations less than or equal to 60 mg/dl (less than or equal to 3.3 mmol/L), mean 6 AM glucose concentration was 95 +/- 6 mg/dl (5.7 +/- 0.3 mmol/L) and less than or equal to 100 mg/dl in 68.6%. In only 4.3% of these cases was the 6 AM glucose concentration greater than 200 mg/dl (greater than 11.1 mmol/L). Among patients who experienced 2 AM hypoglycemia, after-breakfast glucose values were not greater on days with 2 AM hypoglycemia than on days without it. These data indicate that 2 AM hypoglycemia is relatively common in patients with insulin-dependent diabetes mellitus, is frequently preceded by a 10 PM glucose value less than or equal to 5.6 mmol/L, and is less well predicted by other factors. Appropriate treatment of 2 AM hypoglycemia seldom results in either before-breakfast or after-breakfast blood glucose values greater than 200 mg/dl (greater than 11.1 mmol/L). Early-morning hypoglycemia is an uncommon cause of otherwise unexplained, prebreakfast hyperglycemia in children with insulin dependent diabetes mellitus. PMID- 2184212 TI - Linear growth during long-term treatment with somatostatin analog (SMS 201-995) for persistent hyperinsulinemic hypoglycemia of infancy. PMID- 2184213 TI - Prediction of the need for transfusion during anemia of prematurity. AB - We reviewed erythrocyte transfusions, given after 2 weeks of age to premature infants, to derive patient selection criteria for trials of administration of recombinant human erythropoietin to maintain hematocrit during the anemia of prematurity. We first studied 122 infants, less than 36 weeks of gestational age, who remained in a level 3 nursery longer than 4 weeks. Multiple logistic regression analysis was used to select those variables associated with more than two transfusions after the second week; these included gestational age, 5-minute Apgar score, transfusion during the first week, and patent ductus ligation. The best predictor, alone or combined, was gestational age less than 30 weeks. This predictor was applied to a second population of 44 premature infants from a level 2 nursery, and we found a 94% probability of excluding those infants who did not receive a transfusion. This information will allow selection of premature infants who are candidates for administration of recombinant human erythropoietin. PMID- 2184214 TI - Erythroid "burst promoting" activity in serum of patients with the anemia of prematurity. PMID- 2184215 TI - Reflux nephropathy secondary to intrauterine vesicoureteric reflux. AB - In 107 infants with 182 antenatally diagnosed urinary tract anomalies, 24 had either unilateral (12) or bilateral (12) vesicoureteric reflux (VUR). The VUR was more common in boys (male to female ratio, 16:8) and usually severe (grades IV [16], III [10], II [4], and I [6]). Intravenous pyelography showed the changes of atrophic pyelonephritis in 10 refluxing units, and in another two with an associated pelviureteric junctional hydronephrosis. Lateral ectopia of the ureteric orifices was noted in six of these 10 refluxing renal units. Isotopic renography showed a reduction in function in nine of the 14 patients examined, ranging between 9% and 41%. (45% and above was considered within the normal range). Only two patients developed a urinary infection before intravenous pyelography or isotopic renography was performed, suggesting that renal changes noted were primary rather than secondary. Findings support the hypothesis that foetal VUR may be a contributing factor in the causation of atrophic pyelonephritis (foetal reflux nephropathy) observed in these patients. PMID- 2184217 TI - Effects of sympathetic activation on plasma renin activity in the developing rat. AB - The present experiments studied the ontogeny of sympathetic control of the renin angiotensin system by using pharmacological agents, which act at different levels of the sympathetic axis, to increase plasma renin activity (PRA) during the preweanling period in Sprague-Dawley rats. The selective beta-1 adrenoceptor agonist, prenalterol, produced age- and dose-dependent PRA increases. In 5- and 10-day-old animals, prenalterol treatment produced minimal stimulation of PRA and the dose-response curve was essentially flat. In contrast, greater PRA responses to increasing doses of prenalterol were found in 15- and 20-day-old animals. The PRA response to tyramine, which causes norepinephrine release from postganglionic sympathetic fibers, gradually increased between 5 and 20 postnatal days of age, first producing significant stimulation on day 15. Centrally mediated sympathetic activation with yohimbine also produced age-dependent stimulation of PRA that was comparable to the increases produced by tyramine between postnatal days 10 and 20. However, in contrast to tyramine, yohimbine produced a significant increase in PRA on postnatal day 5. The present results suggest that functional sympathetic control of the renin-angiotensin system matures during the second to third postnatal week in the Sprague-Dawley rat, and this may be related to the development of beta-1 adrenoceptors in the kidney that regulate renin release. PMID- 2184218 TI - Histamine and methacholine aerosol bronchial challenge in awake guinea pigs. AB - Cardiopulmonary responses to histamine and methacholine aerosol challenge were examined and compared in unanesthetized spontaneously breathing guinea pigs. All animals had surgically implanted intrapleural catheters and some had arterial or right heart catheters as well. Animals were placed in plethysmographs and exposed to ascending doses of aerosolized agonists. The provocative dose, i.e., the dose that caused a clear bronchospastic response, was defined as the concentration that increased intrapleural pressure to at least 20 cm H2O. Results showed that bronchospasm was characterized further by decreases in dynamic lung compliance and arterial PO2 and an increase in airway resistance. The accumulation of trapped gas in the lung, after challenge, measured in the excised collapsed lung correlated with the increase in intrapleural pressure and with the fall in lung compliance. Male guinea pigs between 3- and 15-weeks of age did not vary in sensitivity to histamine. Methacholine and histamine were equipotent and produced similar responses. Tachyphylaxis was not demonstrated for either compound. In addition, the provocative dose for the drugs remained stable on a day-to-day basis. These results offer insight into the nature of the bronchospastic response in guinea pigs and provide new data on response to methacholine. PMID- 2184219 TI - A light-cured interim obturator prosthesis. A clinical report. AB - A new method of making a maxillary interim hollow obturator prosthesis is presented. The light-cured resin allows the dentist to make and deliver the prosthesis at the same visit with minimal time and equipment. PMID- 2184216 TI - Carrier-mediated transport in the hepatic distribution and elimination of drugs, with special reference to the category of organic cations. AB - Carrier-mediated transport of drugs occurs in various tissues in the body and may largely affect the rate of distribution and elimination. Saturable translocation mechanisms allowing competitive interactions have been identified in the kidneys (tubular secretion), mucosal cells in the gut (intestinal absorption and secretion), choroid plexus (removal of drug from the cerebrospinal fluid), and liver (hepatobiliary excretion). Drugs with quaternary and tertiary amine groups represent the large category of organic cations that can be transported via such mechanisms. The hepatic and to a lesser extent the intestinal cation carrier systems preferentially recognize relatively large molecular weight amphipathic compounds. In the case of multivalent cationic drugs, efficient transport only occurs if large hydrophobic ring structures provide a sufficient lipophilicity hydrophilicity balance within the drug molecule. At least two separate carrier systems for hepatic uptake of organic cations have been identified through kinetic and photoaffinity labeling studies. In addition absorptive endocytosis may play a role that along with proton-antiport systems and membrane potential driven transport may lead to intracellular sequestration in lysosomes and mitochondria. Concentration gradients of inorganic ions may represent the driving forces for hepatic uptake and biliary excretion of drugs. Recent studies that aim to the identification of potential membrane carrier proteins indicate multiple carriers for organic anions, cations, and uncharged compounds with molecular weights around 50,000 Da. They may represent a family of closely related proteins exhibiting overlapping substrate specificity or, alternatively, an aspecific transport system that mediates translocation of various forms of drugs coupled with inorganic ions. Consequently, extensive pharmacokinetic interactions can be anticipated at the level of uptake and secretion of drugs regardless of their charge. PMID- 2184220 TI - Emergence profiles in natural tooth contour. Part II: Clinical considerations. AB - Selection of the straight emergence profile in designing artificial crowns for teeth has been shown to improve the effectiveness of oral hygiene near the gingival sulcus. The axial profile of teeth can be viewed as a series of straight lines with curved transitions. Reproduction of these geometric patterns facilitates fabrication of restorations that appear natural. PMID- 2184221 TI - The influence of condensation method on porosity and shade of body porcelain. AB - Condensation of porcelain is an important laboratory variable that can affect a variety of physical properties in metal ceramic restorations. This study examined four methods of condensation (brush with vibration, ultrasonic vibration, spatulation, and noncondensation) to evaluate their effects on porosity and color. Standardized 12 x 12 mm acetate plastic squares were invested and cast with Olympia alloy. After oxidation, the metal substructures received one of the following opaque and body porcelains: Ceramco II G Series, Will-Ceram V-Series, Vita VMK-68, or Jelenko. The examination of each sample consisted of three parts: (1) apparent specific gravity analysis (porosity); (2) tristimulus colorimeter analysis; and (3) subjective observer color analysis. No statistical differences (p less than or equal to 0.05) in apparent specific gravity were found between methods of condensation within any of the four porcelains. Statistical differences (p less than or equal to 0.05) in color were noted between methods of condensation within several of the porcelains by both the tristimulus colorimeter and the subjective observers. PMID- 2184222 TI - Evaluation of the relationship between anterior and posterior functionally disclusive angles. Part I: Literature review, instrumentation, and reproducibility. AB - Authors are not in agreement concerning the existence of an anatomofunctional interrelationship between condylar and anterior guidances of the mandible in humans. Current literature consists either of speculative statements or studies omitting the role of the meniscus. This article (part I) describes a unique method to correlate the condylar functional anatomy to the lingual inclines of the maxillary anterior teeth (anterior guidance) and acknowledges all components of the temporomandibular joint. The measurements obtained by means of this method were reproduced five different times on five different subjects, making possible a valid statistical analysis of the correlation between condylar and anterior guidances of the mandible (part II). PMID- 2184223 TI - Effects of the temperature of cooling water during high-speed and ultrahigh-speed tooth preparation. AB - In vitro measurements of heat production in the pulp chamber during tooth preparation were performed on intact third molars. The experiments were designed to simulate physiologic temperature conditions in the tooth and oral cavity and to standardize parameters of tooth preparation. Two drive systems, the turbine and the high-speed angle, were compared by using two ranges of cooling water temperature. The critical temperature of 41 degrees C to 42 degrees C that is irreversibly harmful to pulpal tissue was not reached with a cooling water temperature of 30 degrees C to 34 degrees C. Because the temperature elevation during turbine preparation was dependent on the diminishing thickness of remaining dentin, in preparing teeth close to the pulp, a high-speed angle was advantageous. PMID- 2184224 TI - Effect of opaque porcelain application on strength of bond to silver-palladium alloys. AB - The opaque porcelain layer for porcelain-fused-to-metal restorations is critical for success. This investigation examined opaque porcelain application using one- and two-layer techniques with respect to their effect on the strength of bond to three silver-palladium alloys. There were no significant differences in the flexural bond strengths of the three alloys for the one- and two-layer opaque application techniques. With respect to bond strength, these results afford flexibility in the choice of the one- or two-layer techniques. PMID- 2184225 TI - Bond strengths of luting cements to potassium oxalate-treated dentin. AB - Potassium oxalate is gaining popularity as a dentin treatment to prevent the development of dentin sensitivity. Because treated dentin surfaces are covered with calcium oxalate crystals, the bond strength of cements to oxalate-treated dentin required investigation. This study determined the tensile bond strengths of glass-ionomer, polycarboxylate, and zinc phosphate cements used to cement castings to dentin treated with either water or potassium oxalate. The results indicate that oxalate-treated dentin did not affect the bond strength of glass ionomer or polycarboxylate cements, but produced a large decrease in the bond strength of zinc phosphate cement. PMID- 2184226 TI - Occlusal accuracy of casts made and articulated differently. AB - This study evaluated the occlusal accuracy of gypsum casts constructed from irreversible hydrocolloid and selected nonaqueous elastomeric materials. Master metal casts were attached to a vertically moving apparatus that allowed their occlusal surfaces to produce repeatable contacts. Impressions were made with irreversible hydrocolloid, polysulfide, and vinylsiloxane. Resulting maxillary casts were mounted with a constant positioning device and mandibular casts were mounted with zinc oxide-eugenol paste records or by maximum intercuspation. Four specific master occlusal contacts were compared with contacts generated from the mounted gypsum casts; a perfect score was 40 (four contacts x 10 casts). A chi square linear model for category data was used to compare groups. Results indicated that casts made from irreversible hydrocolloid should not be articulated with the use of a zinc oxide-eugenol paste but are best articulated by using maximum intercuspation (32/40 contacts). PMID- 2184227 TI - Liquid-supported dentures. Part II: Clinical study, a preliminary report. AB - A clinical study was made of 11 selected patients wearing liquid-supported dentures. The experiences and opinions of the patients were assembled and the results are discussed. The most important conclusions of this study are that it is possible to make a liquid-supported denture that in general fits and feels comfortable, has proper retention, a slightly diminished masticatory function, and that can provide a solution to some problematic prosthodontic situations. PMID- 2184228 TI - An in vivo replica method for the site-specific detection of Candida albicans on the denture surface in denture stomatitis patients: correlation with clinical disease. AB - A site-specific agar replica technique for detecting Candida albicans on the acrylic resin denture surface of denture stomatitis patients has been developed. The method is selective for C. albicans during a finite incubation period with a specific synthetic growth medium. C. albicans colonies can be geographically observed on the replica and their presence can be correlated with inflammatory lesions visible on the mucosa of the maxillary and mandibular residual ridges. In 12 denture stomatitis patients studied, a close clinical correlation of Newton type III patients was noted but this clinical correlation could not be observed in Newton type I and II patients. In general, the number of C. albicans colonies increased with the severity of the inflammation. The findings are discussed in light of lack of knowledge of the etiology of the stomatitis. The importance of the replica method is also discussed. PMID- 2184229 TI - An evaluation of impression techniques for osseointegrated implants. AB - A passive fit between osseointegrated implants and the prosthesis they will support has been advocated. An experimental model was developed to test the accuracy of three impression techniques and the components used to make the transfer records. Statistically, no significant difference was found between the three methods tested. From this initial study, it appears that further work is needed to isolate techniques that will predictably provide accurate registration of the position of endosseous implants. PMID- 2184230 TI - Fabrication of a prosthesis to prevent sleep apnea in edentulous patients. AB - This article describes clinical and laboratory technique to use in the fabrication of a prosthesis to prevent sleep apnea in the edentulous patient. The objective of the treatment is to establish a comfortable protrusive and vertical posture of the mandible that prevents or minimizes obstruction of the airway during sleep. During fabrication of the prosthesis, cephalograms are used to assess spatial changes between the base of the tongue and the posterior pharyngeal wall. PMID- 2184231 TI - The longitudinal clinical effectiveness of osseointegrated dental implants: the Toronto study. Part I: Surgical results. AB - In this prospective study, 46 edentulous patients who had undergone traditional denture optimization therapy without success were treated with osseointegrated implants according to the surgical protocol described by Dr. P.I. Branemark. Two hundred seventy-four implants were placed in 49 dental arches--43 mandibles and six maxillae. At the time of writing, 4 to 9 years after insertion of the implants, 244 or 89.05% remained osseointegrated. Of the 262 implants in place more than 5 years, 232 or 88.55% were still integrated. The implant success criteria developed in this clinical study endorsed the predictably favorable outcome of the Branemark technique. PMID- 2184232 TI - A finite element survey of eleven endosseous implants. AB - Eleven different post-type endosseous implants were biomechanically analyzed by use of the finite element method to compile a list of features that could be used to design an optimal post-type endosseous implant. Stress magnitudes and contours within each implant and within the surrounding bone were calculated. Implant features causing high stresses and low stresses, possibly contributing to pathologic bone resorption and bone atrophy were noted. Although this preliminary survey was not complete, tentative suggestions in implant design for improved implant performance were made. PMID- 2184233 TI - Devices for the diagnosis and treatment of temporomandibular disorders. Part III: Thermography, ultrasound, electrical stimulation, and electromyographic biofeedback. AB - This last article in the three-part series on devices for the diagnosis and treatment of temporomandibular disorders (TMD) compared the claimed diagnostic usefulness of thermography with the present scientific evidence. In a similar manner, the therapeutic efficacy of ultrasound, electrical stimulation, and electromyographic biofeedback was also reviewed. This evaluation concluded that the application of thermography to the diagnosis of TMD is limited by variations within and among subjects and by intrinsic problems with controls of the test environment. It also concluded that evidence that therapeutic ultrasound alone is useful for the treatment of TMD is lacking, that positive clinical results of electrical stimulation may not be due to specific therapeutic effects, and that it is doubtful that the use of electrical stimulation devices can produce a position of the mandible that has any diagnostic or therapeutic significance. There is evidence, however, that relaxation training, assisted by EMG biofeedback, can reduce daytime muscle activity. PMID- 2184234 TI - Monopoly coating on acrylic resin surfaces: a bacteriologic study. AB - In an open bulb of a buccal flange obturator, it is almost impossible to polish the inner surface of the bulb. Because it cannot be cleaned easily, oral and nasal secretions lead to odors. To obtain a smoother surface, it is suggested that monopoly be painted on the unpolished surface of the open bulb. In this study, the effect of a monopoly coating on bacteria retention and washability of acrylic resin surfaces was investigated. Coated and uncoated acrylic resin samples were prepared and both were contaminated with Escherichia coli. After standard washing, the remaining viable E. coli colonies were counted. The statistical results showed that the difference in the number of E. coli colonies between coated and uncoated groups was highly significant (p less than 0.001). It was suggested that monopoly should be applied to the acrylic resin surfaces where mechanical polishing cannot be done. PMID- 2184235 TI - The bond strength of a visible light-cured reline resin to acrylic resin denture base material. AB - The introduction of Triad visible light-cured denture resin has led to several applications. Among them is direct intraoral relining of complete and partial dentures. This study investigated the bonding characteristics of Triad reline resin to four commonly used heat-cured denture base resins. The shear and tensile bond strengths of Triad resin and four denture base resins were determined and compared with intact tensile strengths. The findings of this study indicate that the bond strength of Triad resin to denture base resin is sufficiently high to suggest its clinical applicability. PMID- 2184236 TI - Biphasic production of antisperm autoantibodies follow vasectomy of the Lewis rat. AB - Temporal changes in the specificity of post-vasectomy autoantibodies to SDS-PAGE separated sperm antigens were investigated in Lewis rats. Sera were obtained from nine vasectomized animals prior to vasectomy, every two weeks for 14 weeks, and less frequently thereafter, up to 41 weeks. Changes in antisperm autoantibodies over time were assessed by ELISA and western blot assay and compared to antisperm isoantiserum and normal Lewis rat serum. A "biphasic" pattern of autoantibody production over time was observed in a majority of individuals. This pattern was characterized by early phase autoantibodies, produced between 0 and 6 weeks after vasectomy, which bound antigens at the stacking, separating and ionic fronts and by late phase autoantibodies, produced after 4 weeks following vasectomy which bound antigens at 86, 63, 52, 43, 31 and 26 kDa. Previous work suggested that some high molecular weight autoantigens were disulfide-bonded polymers of the polypeptides at 86, 63, and 43 kba (Handley, et al., 1988). Indirect immunofluorescence with monospecific isoantisera to the 86 kDa autoantigen suggested that its corresponding high molecular weight polymer was located in the tail of cauda epididymal spermatozoa. This polymer possessed several characteristics of T cell independent autoantigens. These data show a change in the specificity of autoantibodies produced over time after vasectomy which may reflect a shift from T cell independent to T cell dependent autoantibody production by the Lewis rat. PMID- 2184237 TI - Hydroxyethylamine analogues of the p17/p24 substrate cleavage site are tight binding inhibitors of HIV protease. PMID- 2184238 TI - Renin inhibitory peptides. A beta-aspartyl residue as a replacement for the histidyl residue at the P-2 site. AB - In an effort to decrease the size and to increase the hydrophilicity of the previously prepared renin inhibitory peptides, it was postulated that one might be able to take advantage of the polar Thr-84 on the flap region of the enzyme renin by potential hydrogen bonding to polar functionality on the inhibitory peptide at the P-2 site. A beta-aspartyl residue with a carboxylic acid group was proposed to be a possible replacement for the histidyl residue at the P-2 site. A series of renin inhibitory peptides were prepared with the beta-aspartyl residue to probe the structure-activity relationship of the resulting peptides. Potent inhibitory peptides could be realized with activity in the subnanomolar range. Molecular modeling was also undertaken to investigate the interactions between the enzyme active site and the new inhibitors and to suggest a possible mode of binding of these ligands to the enzyme. From this modeling study, the role of Ser 229 at the active site in the bound conformer of the inhibitors was suggested. It was further noted in the analogue study that a malic acid residue, which is the oxygen analogue of the beta-aspartic acid residue, could lead to further enhancement of inhibitory potency of congeneric peptides. Small renin inhibitors, such as compound XII with molecular weight 535 and with no alpha-amino acid residue, could be prepared and exhibited renin inhibitory activity in the nanomolar range. PMID- 2184239 TI - Crystallization of the soluble lytic transglycosylase from Escherichia coli K12. AB - Lytic transglycosylases degrade the murein polymer of the bacterial cell wall to 1,6-anhydromuropeptides. These enzymes are of significant medical interest, not only because they are ideal targets for the development of new classes of antibiotics, but also because the low molecular weight products of their catalytic action can cause diverse biological activities in humans, which can be either beneficial or toxic. A soluble lytic transglycosylase was purified from an overproducing Escherichia coli strain and X-ray quality crystals were obtained at room temperature from hanging drops by vapor diffusion against 20 to 25% (NH4)2SO4, in 100 mM-sodium acetate buffer, pH 5.0. The crystals diffract in the X-ray beam to 2.8 A resolution. Their space group is P2(1)2(1)2(1) with cell dimensions a = 81 A, b = 88 A and c = 135 A. Assuming one monomer (Mr 70,362) per asymmetric unit, the solvent content of these crystals is 63%. PMID- 2184240 TI - Genomic organization and physical mapping of the transfer RNA genes in Escherichia coli K12. AB - By using a set of 476 ordered DNA clones (in lambda phage vector) that covers the entire chromosome of Escherichia coli K12, we have made an exhaustive survey of tRNA genes in the E. coli genome. Ultraviolet-irradiated bacteria were separately infected with each of the 476 clones and the RNA molecules produced upon infection were labeled with 32P. The labeled tRNAs were separated by gel electrophoresis and then characterized by fingerprinting analysis. Fifty-nine of the 476 clones produced tRNAs, including adjacent overlapping ones that share the same tRNA genes. The products of all the previously mapped tRNA genes (about 60, to date) were detected according to their expected positions, and 19 more tRNA genes were newly elucidated. These new tRNA genes were identified by sequencing the DNA from relevant regions of the clones; the DNA sequences were scanned for the stretches that could be folded into the familiar cloverleaf structure and the transcription units were deduced by predicting the promoters and terminators. The total complement of the tRNA genes in E. coli K12 was 78 for 45 tRNA (or 41 anticodon) species, distributed in 40 different transcription units throughout the chromosome. In addition, a gene for selenocysteine tRNA was detected by hybridization and mapped to a specific DNA segment. A comprehensive tRNA gene map of E. coli was constructed, including the selenocysteine tRNA gene. All the tRNA genes encode the 3' CCA, and in several cases the terminal 19 nucleotides (including the 3' CCA) of a tRNA gene is repeated several times. Finally, in the present study the sites for a long inversion (approx. 800 x 10(3) base-pairs, around the oriC region) in Kohara's library was determined to be within the 23 S 5 S regions in rrnD and rrnE, revealing the exchange of combinations of spacer and distal tRNA genes between these two ribosomal RNA operons. PMID- 2184241 TI - Doppler sonographic demonstration of the progressive spontaneous thrombosis of pseudoaneurysms. AB - In three patients with diagnosed pseudoaneurysms, surgical intervention was delayed because of the patients' clinical condition. In successive follow-up examinations in one patient, development of a new lobe to the previously single lobed pseudoaneurysm was noted with progressive centripetal thrombus formation in each lobe leading to the eventual complete thrombosis of the pseudoaneurysm without surgical intervention. The sequence of steps leading to the complete thrombosis of the pseudoaneurysm as seen by color Doppler and pulsed Doppler examination is described. In two other patients with a single-lobed and a multilobed pseudoaneurysm, respectively, follow-up examinations without surgical management revealed complete thrombosis of the pseudoaneurysms. Whereas traditional teaching holds that pseudoaneurysms require surgical repair, this short series of cases suggests that, when progressive centripetal thrombus formation is observed, the pseudoaneurysms can go on to complete thrombosis. Follow-up for up to 4 months reveals no sonographic evidence of rebleeding or other evidence of weakness in the arterial wall at the site of the previous pseudoaneurysms. PMID- 2184242 TI - Fetal lobation. An anatomo-ultrasonographic correlation. AB - Remnants of the fusion of fetal renunculi have been mistaken for renal scars or tumors. We compared anatomic cuts of 24 cadaveric kidneys with fetal lobation (ages ranged from 16 weeks gestation to 49 years) to identical ultrasonographic sections performed in a water bath and to sonograms of healthy persons of similar ages as the cadavers. Fetal lobation was characterized as follows: there were fine, linear demarcations indenting the renal surface, separating normal lobes, consisting of a central pyramid and surrounding cortex. Separate renunculi seen in early fetal life progressively fuse throughout gestation, leaving interlobar grooves. During the third trimester, the renal surface becomes smoother and the interlobar grooves become invisible. One prominent indentation of the renal surface, the interrenuncular junction, incorporates perirenal fat and invaginates the anterior surface of the upper third of the kidney to the hilum and is the most easily visible remnant of fetal lobation. The sharply defined linear remnants of interlobar grooves should not be mistaken for scars, which are wider, less well defined and always associated with loss of renal cortex. PMID- 2184243 TI - Combined Doppler and morphologic sonographic evaluation of renal transplant rejection. AB - We sought to evaluate whether results of Doppler ultrasound alone or in combination with morphologic sonographic evaluation could predict acute renal transplant rejection accurately enough to avoid biopsy. Seventy-one patients were evaluated at time of biopsy. A resistive index greater than 0.90 was 100% predictive of acute rejection, but sensitivity was only 26%. Resistive indices in acute and chronic rejection were often similar. When all morphologic features were abnormal (11%), acute rejection was uniformly present. Regression analysis selected resistive index over morphologic features for ability to predict acute rejection. When resistive index is greater than 0.90 or all morphologic features are abnormal, acute rejection can be predicted with high accuracy, but biopsy remains necessary in many cases. PMID- 2184244 TI - Doppler diagnosis of partial vertebral/subclavian steals convertible to full steals with physiologic maneuvers. AB - Subclavian steal syndrome has been classically described as a unidirectional phenomenon in which retrograde flow occurs in the ipsilateral vertebral artery in cases of high-grade proximal subclavian stenosis. Pulsed Doppler examination in cases of subclavian stenosis shows that partial steals with to-and-fro flow do occur. A model based on fluctuating pressure gradients to explain the partial steal phenomenon is discussed. The usefulness of physiologic maneuvers such as ipsilateral arm exercise and postocclusive hyperemia in converting partial steals to full steals is demonstrated. In cases in which surgical bypass to correct partial steals is carried out, a relative steal can be demonstrated by Doppler examination before and after physiologic maneuvers. PMID- 2184245 TI - Texture in tissue echograms. Speckle or information? AB - Models of biological tissues are described in terms of acoustic parameters and of structure. Beam formation is discussed for continuous wave and pulsed modes of transducer operation and the concept of the point spread function (PSF) is introduced. The PSF is equivalent to the resolution cell, or the sampling volume, of echographic equipment. The generation of echograms from parenchymal tissues is described in terms of speckle formation due to interference at reception on the transducer. The speckle dimensions are quantitatively compared to the sampling volume of the employed transducer. It is shown that for fully developed speckle the tissue characteristics are exclusively reflected in the mean echolevel and not in the speckle size. The speckle size is, however, greatly dependent on the bandwidth, the frequency, and the geometry of the employed transducer. The attenuation by the insonated tissue yields a depth-dependent increase of mainly the lateral speckle size, in addition to the depth dependence caused by the beam formation. If the number density of scattering sites within the tissue is relatively low, the speckle characteristics are dependent on this density and, hence, tissue characterization is feasible if these characteristics are analyzed by statistical methods. These methods are gray level histogram analysis and the estimation of the autocorrelation function, ie, first and second order statistics, respectively. Structural order in tissues can be quantified by autocorrelation analysis and clinical studies on diffuse liver diseases support this conclusion. The effects of pre- and postprocessing on the detectability of focal lesions are outlined. The impact of multifocus systems and of the acquisition of radio frequency echograms on further developments of clinical echography is discussed. PMID- 2184246 TI - Empty bicipital groove due to rupture and retraction of the biceps tendon. PMID- 2184247 TI - Thrombosis of a duplicated superficial femoral vein. Potential error in compression ultrasound diagnosis of lower extremity deep venous thrombosis. PMID- 2184248 TI - Lymphoma presenting as allograft hematoma in a renal transplant recipient. PMID- 2184249 TI - Motion marking in color Doppler ultrasound needle and catheter visualization. PMID- 2184250 TI - Encapsulated paravesical foreign body. AB - A large, round, paravesical mass was surgically removed from a 65-year-old man. The mass was an encapsulated aseptic granuloma surrounding a gauze that was left in situ 10 years previously at hernioplasty. PMID- 2184251 TI - Disseminated actinomycosis presenting as a testicular mass: a case report. AB - Actinomycosis of the testicle is a rare clinical entity. A review of the literature reveals only 7 case reports. Patients require prolonged therapy with antibiotics, usually penicillin. Many patients with less severe forms of the disease improve on antibiotics alone. Surgical intervention is reserved for confirming the diagnosis, treatment of abscesses, excision of sinus tracts and drainage. We report case 8 in the literature and review the previous reports. PMID- 2184252 TI - Clonal growth requirements of human bladder tumor cell lines. AB - We have serially investigated the role of nutrients and growth factors for their ability to support the clonal growth of human bladder tumor cell lines. Five established human bladder tumor cell lines were selected for study of their requirements for clonogenic growth in semisolid cultures. We identified an "optimal medium" to be Alpha MEM medium, 15% horse serum, five micrograms/ml. of transferrin, five micrograms/ml. of insulin and 30 ng./ml. of epidermal growth factor. The "optimal assay" enhanced the growth of human bladder tumor cell lines 2.5 times compared to the standard clonogenic assay. The resulting medium is less complicated to maintain, less expensive and supports the growth of human bladder tumor cell lines better than the standard clonogenic assay. PMID- 2184253 TI - Sports hematuria. AB - Strenuous exercise makes extraordinary demands. The transition from rest to intensive physical activity can cause pathological changes in various organs, particularly in the urinary tract. Hematuria (microscopic or macroscopic) is one of the abnormalities commonly found after sports activity. This phenomenon can occur in noncontact sports (such as rowing, running and swimming) as well as in contact sports (boxing, football and so forth). The pathophysiology can be either traumatic or nontraumatic. Renal trauma and/or bladder injury due to repeated impact of the posterior bladder wall against the bladder base can cause vascular lesions and consequently hematuria. There are 2 mechanisms of nontraumatic injury. 1) Vasoconstriction of the splanchnic and renal vessels occurs during exercise in order that blood can be redistributed to the contracting skeletal muscles, thus causing hypoxic damage to the nephron. This results in increased glomerular permeability which would favor increased excretion of erythrocytes and protein into the urine. 2) A relatively more marked constriction of the efferent glomerular arterioli results in an increased filtration pressure, which favors increased excretion of protein and red blood cells into the urine. It must be noted that sports hematuria differs from other conditions that may cause reddish discoloration of the urine due to physical exercise, such as march hemoglobinuria and exercise myoglobinuria. In the latter 2 abnormalities there is excretion of hemoglobin and myoglobin molecules in the urine and not whole blood or intact red blood cells. Sports hematuria usually has a benign self-limited course. However, coexisting urinary tract pathological conditions should be excluded carefully. PMID- 2184254 TI - Bladder volume determination using a dedicated, portable ultrasound scanner. AB - Urethral catheterization, the standard method for measurement of bladder volume, is associated with patient discomfort plus the risks of urethral trauma and urinary tract infection. A portable ultrasound instrument that automatically determines bladder volume was used for 164 determinations and the digital readout correlated with the catheterized volume (r2 equals 0.79). This instrument is a noninvasive alternative to urethral catheterization for the determination of bladder volume in most patients. PMID- 2184255 TI - Comparison of penile duplex ultrasonography with nocturnal penile tumescence monitoring for the evaluation of erectile impotence. AB - A total of 50 patients with erectile dysfunction underwent comprehensive evaluation, including vascular evaluation with penile duplex ultrasonography and papaverine injection, as well as nocturnal penile tumescence monitoring. The latter was performed in a sleep laboratory setting in all patients. The results of penile duplex ultrasonography with papaverine injection were classified as 18 patients with normal vascular findings, 22 with arterial insufficiency, 3 with the pelvic steal syndrome and 7 with isolated venous leakage. Of the patients 15 had normal ultrasonographic and nocturnal penile tumescence findings, 29 had abnormal ultrasonographic vascular and nocturnal penile tumescence findings, 3 had abnormal ultrasonographic vascular findings and normal nocturnal penile tumescence (including 1 with the pelvic steal syndrome as evidenced by penile brachial index) and 3 had normal ultrasonographic vascular findings and abnormal nocturnal penile tumescence (including 2 with neurogenic erectile dysfunction). Penile duplex ultrasonography with papaverine injection appears to be a useful objective method to evaluate vasculogenic impotence and to correlate favorably with nocturnal penile tumescence monitoring. It also may have a higher yield than nocturnal penile tumescence monitoring in patients with the pelvic steal syndrome. While nocturnal penile tumescence is impaired in patients with neurogenic impotence, penile duplex ultrasonography with papaverine injection reveals, as expected, normal findings in patients with neurogenic impotence and normal vascular systems. PMID- 2184256 TI - Comparison of selective internal iliac pharmaco-angiography, penile brachial index and duplex sonography with pulsed Doppler analysis for the evaluation of vasculogenic (arteriogenic) impotence. AB - Between July 1987 and February 1988 selective internal iliac angiography was performed before and after intracavernous injection of papaverine plus phentolamine in 43 patients with erectile dysfunction. In 63% of the patients stenosis or occlusion of the pudendal artery was found. The penile brachial index was calculated and duplex sonography with pulsed Doppler analysis was performed in 23 patients. Angiography and penile brachial index correlated in only 39% of the patients, whereas selective internal iliac angiography and duplex sonography correlated in 91% (21 of 23). In 2 patients duplex sonography with pulsed Doppler analysis rendered better information about penile arterial perfusion than did angiography. PMID- 2184257 TI - Transrectal ultrasound appearance of transitional cell carcinoma involving the prostate. AB - Prostatic involvement with transitional cell carcinoma of the bladder is common. Surveillance for prostatic invasion consists primarily of cystoscopic examination of the urethra. Unfortunately, transitional cell carcinoma may involve other regions of the prostate that are inaccessible by cystoscopy. A total of 58 men with transitional cell carcinoma of the bladder underwent transrectal ultrasound before cystoprostatectomy or, in some cases, ultrasound-guided prostate biopsies and subsequent cystoprostatectomy. Prostatic involvement was found in 20 patients (34.5%). Of those patients 10 (50%) demonstrated prostatic urethra invasion, 7 (35%) stromal invasion, 4 (20%) ejaculatory duct and seminal vesicle invasion, and 3 (15%) involvement of the periprostatic tissues. Invasion of the prostatic urethra was not detected by transrectal ultrasound but 5 of the 7 stromal lesions exhibited hypoechogenicity. All cancer-laden ejaculatory ducts were hypoechoic on ultrasound examination. All cases of periprostatic involvement were also detectable by corresponding areas of hypoechogenicity. Transrectal ultrasound may enhance the surveillance of men with transitional cell carcinoma. PMID- 2184258 TI - Gas-forming infection of the urinary tract: an investigation of fermentation as a mechanism. AB - Most gas-forming infections occur in patients with diabetes. Carbon dioxide formation, resulting from fermentation of the high concentration of sugar in the urine and tissue by infecting organisms, was regarded as the key factor of gas formation in previous reports. Gas from an emphysematous infection of a polycystic kidney was analyzed to understand better the mechanisms involved in gas-forming infections of the urinary tract. The term emphysematous renal polycystic infection is proposed for this particular condition. Gas from the cysts contained 4.1% carbon dioxide, 10.5% oxygen, 67.3% nitrogen and 18.1% unknown gas. This finding is astonishingly similar to that of Wheeler in 1954 and cannot be fully explained by the sugar fermentation theory. Therefore, we propose a new hypothesis. Impaired transportation of gas produced by rapid catabolism leads to gas accumulation in the tissue, which will gradually expand and create chambers to form gas bubbles. Gas of adjacent tissues will attempt to come into equilibrium with the gas bubbles. Positive equilibrium will lead to continuous expansion of the lesion bubble. However, if the chamber is unable to withstand the increasing pressure then rupture or spontaneous drainage of the gas bubble may occur. During negative equilibrium gas in the bubble gradually simulates tissue gas with eventual shrinkage of the bubble. If the chamber is unable to sustain the pressure it collapses and the bubble disappears. However, if the chamber is capable of sustaining the pressure the bubble still may persist even when the gas content is equivalent to tissue gas. This hypothesis may lead to better understanding of emphysematous infections of the urinary tract and also may cast light on emphysematous infections of other organ systems. PMID- 2184259 TI - Leiomyoma of the kidney: presentation of 4 new cases and the role of computerized tomography. AB - Renal leiomyoma is a challenging diagnostic and therapeutic condition. It is clinically similar in presentation and radiographic appearance to its malignant counterpart, leiomyosarcoma. We review 30 cases of clinically diagnosed leiomyoma of the kidney from the literature, including 4 new cases with emphasis on the computerized tomography findings. Computerized tomography may locate a renal leiomyoma serendipitously in an asymptomatic patient. If the lesion is peripheral or in the parapelvic area and a plane can be seen between the tumor and kidney a capsular tumor, such as a leiomyoma of the kidney, might be considered in addition to the more common renal cell carcinoma. Renal leiomyomas have a variable radiographic pattern from that of a pure cystic to a mixed solid/cystic to an entirely solid lesion. Renal leiomyomas usually are sharply demarcated from the surroundings. Although computerized tomography cannot distinguish a renal leiomyoma from other benign or malignant renal processes the presence of invasion can virtually eliminate this benign tumor as a diagnosis. Since a preoperative diagnosis cannot be made, management involves renal exploration and radical nephrectomy in the larger lesions with a renal-sparing operation possible in selected cases. After treatment patients have a uniformly excellent prognosis. PMID- 2184260 TI - Fine needle aspiration biopsy in the diagnosis of renal angiomyolipoma. AB - Exclusive reliance on radiographic techniques for the diagnosis of renal angiomyolipoma can lead to misdiagnosis when the histological status is atypical, computerized tomographic findings are equivocal or renal cell carcinoma coexists. We report our experience and those of others in combining fine needle aspiration biopsy and radiological imaging to identify renal angiomyolipoma. Fine needle aspiration biopsy is safe and provides accurate histological diagnosis of renal angiomyolipoma. PMID- 2184261 TI - Evaluation of hematuria in adults. PMID- 2184262 TI - 'What's in a name?' The Paperwork Reduction Act. PMID- 2184263 TI - Diagnostic and therapeutic technology assessment. Prophylactic treatment for opportunistic infections in HIV-positive patients: aerosolized pentamidine. AB - The DATTA panelists considered aerosolized pentamidine to be both safe and effective for primary and secondary prophylaxis of PCP. T4 helper cell counts offer guidance as to the best candidates for primary prophylaxis. Patients with a T4 helper cell count of fewer than 200/mm3 are the most appropriate group to receive primary prophylaxis with aerosolized pentamidine. However, T4 helper cell counts are not an exclusive criterion for aerosolized pentamidine prophylaxis. Some DATTA panelists suggested that certain patients, such as those with Kaposi's sarcoma and lymphomas and those with concomitant human T-cell lymphotropic virus type 1 infection, might be considered candidates for aerosolized pentamidine regardless of T4 helper cell counts. There is no current literature to support this, and this opinion is based solely on clinical experience. Perhaps the use of other markers of immune function (beta 2-microglobulin, neopterin) in conjunction with T4 helper cell counts will give a better indication of when to start primary prophylaxis. Aerosolized pentamidine is not the only potential prophylactic regimen for PCP. Other drugs, including pyrimethamine and sulfadoxine, sulfamethoxazole and trimethoprim, and dapsone, are currently being evaluated. Prior diagnosis and therapy for patients with M tuberculosis must occur before initiation of the use of aerosolized pentamidine. This and other appropriate environmental precautions should reduce transmission of M tuberculosis to health care workers and other patients. Whether any prophylactic treatment of an opportunistic infection will prolong survival in HIV-infected individuals has yet to be proved. The assumption is made, however, that a reduction in opportunistic infections should lower mortality and improve the quality of life. PMID- 2184264 TI - Anesthesiology. PMID- 2184265 TI - Cardiovascular disease. PMID- 2184266 TI - Computers in medicine. PMID- 2184267 TI - Government. PMID- 2184268 TI - Literature of medicine. PMID- 2184269 TI - [Hypercalcemia associated with blast crisis of chronic myeloid leukemia]. AB - We describe a patient with CML who developed hypercalcemia in his course of blast crisis. A 25-years-old man was diagnosed as CML with priapism in April 1985, and controlled with BHAC-DVP, VMP, busulfan therapy. In December 1987, he readmitted to our hospital with abdominal pain. Investigations at that time showed: white blood cell count 11600/microliters (blast cells 9%); hemoglobin 8.4 g/microliters; platelets 19.0 X 10(4)/microliters; serum calcium 13.2 mg/dl; BUN 44 mg/dl; creatinine 2.7 mg/dl. Treatment with predonine, 6-MP and vincristine was begun. But serum calcium level rose gradually up to 16.5 mg/dl. So we tried middle dose Ara-c therapy, serum calcium decreased to 6.8 mg/dl. At once he was in a chronic phase, but he relapsed and died of heart failure. Necropsy showed extensive leukemic blast-cell infiltration of the bone marrow, liver, spleen, lung, and kidney. The cause of hypercalcemia in our case was suspected of local osteolytic hypercalcemia, because multiple bone destruction was found. PMID- 2184270 TI - [Tumor lysis syndrome at the induction therapy of the first remission in two cases of T-ALL]. AB - The anti-tumor therapy followed by tumor lysis syndrome may cause the metabolic disorders including hyperkalemia, hyperphosphatemia and hyperuricemia. It should be known that it occurs frequently in lymphoproliferative diseases, especially in Burkitt's lymphoma. Two cases of T-ALL accompanied by this syndrome, from which the patients were recovered, at the induction therapy of the first complete remission are reported here. Case 1. A 28-year-old man received VP therapy under the diagnosis of T-ALL with massive hepatosplenomegaly and bilateral enlarged kidneys. During the therapy, metabolic disorders with both renal failure and ventricular tachycardia happened. They were resolved by certain series of treatments. The patient was brought to a complete remission with normal size of liver, spleen and kidneys. Case 2. A boy aged 15 having received the intrasubarachnoidal infusion of MTX and 1-Ad-VP therapy under the diagnosis of T ALL accompanied by this syndrome which was improved by an appropriate treatment, and the patient was lead to the remission. The risk factors of this syndrome, such as 1-high drug sensitivity of the tumor; 2-renal dysfunction; 3-rapid cytokinetics of the tumor cell; 4-bigger size of the tumor, as well as the preventive treatment of this syndrome are reviewed. PMID- 2184272 TI - [History of cardiac pacing and pacemaker update]. PMID- 2184271 TI - [Malignant lymphoma with acute renal failure and nephrotic syndrome]. AB - A case of non-Hodgkin's lymphoma with nephrotic syndrome and acute renal failure is described. A 60-year-old Japanese male was admitted to our hospital in November, 1988, because of lymphadenopathy, fever, night sweat, weight loss. On physical examination, lymphadenopathy was present in both cervical, submandibular, supraclavicular, axillary and inguinal regions. The leukocyte count was 9,700/microliters with 85% neutrophils and 2% atypical lymphocytes. Renal function was normal. Lymph node biopsy showed non-Hodgkin's lymphoma of diffuse, large cell type. Immunohistologic examination showed T cell type. A few days later, he fell into acute renal failure. After systemic chemotherapy, he showed prompt improvement in renal function. Echo and computerized tomography (CT) of abdomen revealed no compression of the ureters and bladder. Renal biopsy findings suggested mesangium proliferative glomerulonephritis without invasion of tumor cells. Our case seemed to be rare and was compared with previous reports. PMID- 2184273 TI - [Micromachine in medicine]. PMID- 2184274 TI - [Suppressor glutamine tRNA in retrovirus infected cells]. PMID- 2184275 TI - [Lymphocyte-mediated immunological tests]. AB - Two major types of immune response are present in the body; specific humoral antibody response and specific cell-mediated immune response. Lymphocytes play the major role in cell-mediated immune response, and also control the humoral antibody response. Lymphocyte functions are measured by various laboratory tests, including (1) peripheral lymphocyte count and morphology, (2) lymphocyte surface markers, (3) lymphocyte function tests with lymphocyte culture, (4) histopathological findings of the immune organs such as thymus, lymph nodes, intestinal lymphoid tissue and palatine tonsils. In routine practice, peripheral lymphocyte count and morphology is most commonly used, and then lymphocyte surface markers are measured by flow cytofluorometry using various monoclonal antibodies. PMID- 2184276 TI - [The significance and problem of cyclosporine blood level monitoring]. AB - Cyclosporine, a potent immunosuppressive agent used to prevent rejection of transplanted organs, has a narrow therapeutic range and various toxic effects, mostly concentration-dependent. The kinetics of this drug present a large intra- and interindividual variability due to many factors, resulting in marked variations of blood cyclosporine concentrations, and in a poor correlation between administered dose and concentration. The knowledge of cyclosporine peculiarities and of factors affecting blood concentrations can provide a rational basis for establishing an adequate therapy for the individual patient. Cyclosporine monitoring is a method of evaluating whether the therapeutic choice is correct. Cyclosporine concentrations can be measured in whole blood, plasma, and serum using radioimmunoassay (RIA), high-performance liquid chromatography (HPLC) or fluorescein polarization immunoassay (FPIA). Different results are obtained, depending on the technique and on the biological fluids used. Cyclosporine measurement presents many problems and difficulties. There is a need for standardization and for quality assessment programs. The recent development of monoclonal antibodies may represent a significant advance for cyclosporine monitoring. Therapeutic drug monitoring (TDM) should be undertaken on a regular basis after the initiation of therapy with cyclosporine. PMID- 2184277 TI - [Localization of glycylproline dipeptidyl aminopeptidase in the liver tissue and possible mechanism of its release into blood flow]. AB - We examined the localization of glycylproline dipeptidyl aminopeptidase (GPDAP) in the liver tissue and the mechanism of its release into blood flow. An immunohistochemical study using rabbit polyclonal antibody against the purified GPDAP from human liver obtained at autopsy was performed in liver biopsy samples with the peroxidase-antiperoxidase stain technique. GPDAP staining was detected on the liver cell membrane around bile canaliculi. After treatment with deoxycholic acid (DOC) or Triton X-100, this enzyme disappeared. GPDAP was solubilized rapidly from microsome of human liver by treatment with either DOC or Triton X-100. DOC or Triton X-100 solubilized GPDAP coincided with the isozyme that was the specific isozyme in sera of patients with acute hepatitis or obstructive jaundice. These results suggest that GPDAP localizes on the liver cell membrane around bile canaliculi and that this enzyme is released by the detergent action of bile acids. PMID- 2184278 TI - [Late results of the surgical treatment of patients with biliary calculi]. AB - The authors analyse the late results of surgical treatment of 463 patients who underwent operation for stones in the bile ducts. The late results were found to be determined by the character of the affection of the bile excreting system and the rational choice of the operative method. The indications and contraindications for various methods of treating cholelithiasis were determined more precisely from study of the late results. PMID- 2184279 TI - [Value of ultrasonic examination in the diagnosis of cholelithiasis]. PMID- 2184280 TI - [Surgical treatment of injuries of the intrahepatic bile ducts]. AB - Traumas and cicatricial strictures of the lobar and sectorial hepatic ducts in 9 patients are analysed. The method of operative transillumination vasoscopy was used to exclude devascularization of an isolated intestinal loop. The authors describe the operative techniques and the methods of using bilateral replaceable transhepatic drainage in injuries to the lobar and sectorial hepatic ducts with their bifurcation and trifurcation. PMID- 2184281 TI - [Instrumental examination in focal lesions of the liver]. PMID- 2184282 TI - [Surgical treatment of ruptured abscess of the visceral surface of the liver]. PMID- 2184283 TI - [Recanalization of the bile ducts by roentgeno-endobiliary dilatation and prosthesis (review of the literature)]. PMID- 2184284 TI - [Effect of flying on the health status of pilots in the light of epidemiologic data]. AB - This paper gives an analytical review of epidemiological data about the morbidity and mortality rate of the flying personnel. It shows that the flying personnel differs from the general population in their better health condition which manifests as lower morbidity and mortality rates in every large group of disease. This better health status of the flying personnel may be a result of their adequate selection. The selection makes it difficult to identify relationships between disease and flight effects. Information about these relationships is contradictory and/or insufficient. Proper assessment of flight effects on the health condition of the flying personnel needs further controlled epidemiological investigations. PMID- 2184285 TI - [The surgical treatment of stroke]. PMID- 2184286 TI - Communication disorders and emotional/behavioral disorders in children and adolescents. AB - Recent research in child psychiatry has demonstrated a high prevalence of speech, language, and communication disorders in children referred to psychiatric and mental health settings for emotional and behavioral problems. Conversely, children referred to speech and language clinics for communication disorders have been found to have a high rate of diagnosable psychiatric disorders. Most of the emerging knowledge regarding relationships between communication disorders and psychiatric disorders has been presented in the child psychiatric literature. Speech-language pathologists and audiologists also need to be familiar with this information; an understanding of the complex interrelationship between communication disorders and emotional and behavioral disorders is important for diagnosis, assessment, and treatment. The purpose of this article is to review recent research and discuss clinical implications for professionals in speech language pathology and audiology working with children and adolescents who have, or who are at risk for, developing emotional and behavioral disorders. Issues to be addressed include differential diagnosis, prevention, intervention, and the role of speech-language pathologists serving these children and adolescents. PMID- 2184287 TI - Intravenous amiodarone bolus versus oral quinidine for atrial flutter and fibrillation after cardiac operations. AB - The safety and efficacy of amiodarone and quinidine in reverting atrial tachyarrhythmias after cardiac operations were compared in a randomized cross over trial. Patients with sustained atrial fibrillation or flutter for more than 2 hours' duration, stable hemodynamic status, and prior digoxin therapy were randomized to receive either intravenous amiodarone, 5 mg/kg over 20 minutes (41 patients), or oral quinidine, 400 mg immediately and 400 mg in 4 hours (39 patients), with cross-over at 8 hours if reversion was not achieved. Thirty-six patients had a coronary artery operation, 35 a valvular operation, five had both, and there were four miscellaneous cases. There was a male:female ratio of 1.5:1 and a mean age of 58 years (range 23 to 75 years). Preoperative atrial fibrillation or flutter was present in nine patients, and four patients had an ejection fraction less than 40%. Twenty-five of 39 patients (64%) given quinidine first reverted to sinus rhythm, compared with 17 of 41 patients (41%) given amiodarone first (2p = 0.04). Side-effects occurred in 18 patients given quinidine and five patients given amiodarone (2p = 0.01). Two patients, both given quinidine, were withdrawn from the study. There was no correlation, with either drug, between serum levels and clinical efficacy. Multivariate analysis identified longer times from arrhythmia to treatment, preoperative atrial fibrillation, mitral valve operations, and concomitant propranolol therapy as factors predictive of failure to revert to sinus rhythm. Oral quinidine was more effective than intravenous amiodarone in reverting postoperative atrial fibrillation and flutter but caused more side-effects. PMID- 2184288 TI - Invited letter concerning: resection of tracheal carina for lung cancer. PMID- 2184289 TI - Choline oxidase chemiluminescent assay, after removal of eserine from medium, of acetylcholine released in vitro from brain slices. AB - A chemiluminescent method has been used recently for the determination of acetylcholine with limitations such as the presence of a cholinesterase inhibitor in the incubation medium, which is indispensable for the study of acetylcholine release by various agents. A modified procedure is presented in which the cholinesterase inhibitor eserine (physostigmine) is extracted from the medium. The results showed complete recovery when labelled acetylcholine was used. This modified procedure was used to determine the release of acetylcholine evoked by tityustoxin and ouabain. The results were comparable to those obtained by bioassay using a strip of guinea pig ileum. PMID- 2184290 TI - [The dawn phenomenon in diabetic pregnancy]. AB - The possible development of the dawn phenomenon in three gestational stages was investigated in 9 pregnant women with type I diabetes mellitus and 10 with gestational diabetes. To this end, the overnight intravenous insulin infusion was evaluated with the artificial pancreas (Biostator). In none of the two clinical conditions and in none of the three gestational stages an increased insulin infusions during the second period of the night was found under the experimental conditions of our study. This finding may we related with the timing of the last food intake. PMID- 2184291 TI - [Cryobiology: a new science]. PMID- 2184292 TI - [The importance of anti-oxidants in human nutrition]. PMID- 2184293 TI - [Poisoning caused by metals from food]. PMID- 2184294 TI - [Urinary lithiasis: alternatives to open surgery]. PMID- 2184295 TI - [Alcoholism: prevention beginning at primary care]. PMID- 2184296 TI - [Plasmid spectrum of Escherichia coli]. PMID- 2184297 TI - [Analysis of clinical decisions]. PMID- 2184298 TI - Renin inhibitors. AB - Since the early 1980s, an intensive effort has been focused on the development of orally effective and long-acting inhibitors of renin. During this time, in vitro potency has increased greatly, with several transition-state inhibitor designs yielding inhibitors with subnanomolar IC50 values. In the meantime, both the molecular weight and peptide character of the inhibitors has decreased as important binding elements have been focused into smaller and more stable structures. The resulting inhibitors have shown promising activities in several in vivo models and (in two cases) in man. Nevertheless, renin inhibitors reported to date have limited oral bioavailability and short duration of action, and improvements in both will be necessary for them to compete effectively with ACE inhibitors. Renin inhibitors which have entered clinical studies have at least one naturally occurring amino acid and three or more amide bonds. It is reasonable to expect that continued development will produce wholly nonpeptide inhibitors with still lower MW, and it may be these "second-generation" inhibitors which will succeed as therapeutic agents. Development of orally effective and long-acting inhibitors of renin will enable their long-term antihypertensive efficacy and possible advantages over ACE inhibitor to be investigated. PMID- 2184299 TI - [Increased frequency of group A hemolytic streptococci. Old age and immune deficiency among the risk factors]. PMID- 2184300 TI - [Decision on a new international classification of diseases]. PMID- 2184301 TI - [May the internal iliac artery in the pelvic area be ligated in situ bilaterally for hemostasis? Indications and contraindications]. AB - The bilateral ligation of the internal iliac arteries in situ is successful in preventing haemostasis and the treatment of potentially lethal haemorrhage. In spite of using a resorbable thread (catgut) for ligation a complete recanalization of this large artery could only be observed after nine months in an animal experiment. Clinically this ligation of the artery in situ without severance has not impaired erective potency in patients with an otherwise healthy vascular system. Since many patients did not show any disturbance prior to the vessel's recanalization the early established parallel circulation is sufficient to compensate for the perfusion deficit. A contraindication for the ligation is a previous major procedure, especially, in cases of irradiation or an occlusive vascular disease. PMID- 2184302 TI - The clinical behavior of inverting papilloma of the nose and paranasal sinuses: report of 112 cases and review of the literature. AB - Between 1944 and 1987, 112 patients with inverting papilloma of the nasal cavity were treated. The average duration of follow-up for this population was 6.2 years. The most common symptoms were nasal obstruction and history of previous surgery for nasal "polyps". Recurrence rates were lower when treatment consisted of lateral rhinotomy with medial maxillectomy (14%) vs. transnasal operation with a sinus procedure (35%) or transnasal operation alone (58%). Recurrence rates between men and women were not significantly different when treatment methods were analyzed; however, a higher-than-expected association with tobacco usage was noted. Eight (7%) of the 112 patients had associated nasal carcinoma. Current treatment is lateral rhinotomy with medial maxillectomy to prevent troublesome and potentially malignant recurrent disease. PMID- 2184303 TI - Management of inverted papilloma. AB - This paper updates a 1981 report on the management of inverted papilloma. In that report, routine lateral rhinotomy with en bloc resection of the lateral nasal wall, including the entire schneiderian membrane, was recommended. This report emphasizes the use of computed tomography scanning in management planning. Of 33 patients with inverted papilloma treated between 1969 and 1987, 7 had associated squamous cell carcinoma. Twenty-two patients with IP alone were treated with medial maxillectomy; however, 3 patients have been successfully treated with either a Caldwell-Luc/ethmoidectomy or an external ethmoidectomy for localized disease. The use of computed tomography capable of higher resolution allowed preoperative determination of the extent of disease, enabling the surgeon to plan the surgery more precisely. Patients were followed for an average of 9.6 years. Recurrent disease occurred in one patient (4%) following a lateral rhinotomy/medial maxillectomy approach. The principles set forth in this series of patients remain the same as those previously described due to the unique characteristics of this tumor: its ability to destroy bone, its tendency to recur, and its association with malignancy. The technique of lateral rhinotomy and en bloc excision of the lateral nasal wall, followed by meticulous removal of all mucosa in the ipsilateral paranasal sinuses, remains the standard therapy. PMID- 2184304 TI - [Il'ia Vasil'evich Buial'skii (on the 200th anniversary of his birth)]. PMID- 2184305 TI - [From the distant past of Russian medicine]. PMID- 2184306 TI - Structure-activity relationships in mutagenicity and in nucleophilic ring opening of N-(arylmethyl)phenanthrene 9,10-imines. AB - Ten derivatives of N-benzylphenanthrene 9,10-imine with different substituents on the phenyl ring were synthesized and subjected to mutagenicity tests in Salmonella typhimurium TA100. While electron donating groups were found to enhance the biological activity, electron attracting and bulky substituents lowered the mutagenic potency. A similar dependence on the electronic structure was observed in triethylamine/acetonitrile-promoted interaction of the title imines and 4-nitrothiophenol. This similarity suggests that both biochemical and chemical processes involve mechanisms in which protonation of the aziridine nitrogen is rate controlling, and the attack of the cellular or model nucleophile is a fast step. In contrast to these processes, the reaction of the imines with 4 nitrothiophenol in the presence of 1,5-diazabicyclo[4.3.0] non-5-ene proved to proceed by an SN2 mechanism and to be enhanced by electron attracting substituents. PMID- 2184307 TI - Prediction of the outcome of rodent carcinogenicity bioassays currently being conducted on 44 chemicals by the National Toxicology Program. AB - This paper was written to enable evaluation of the concept that knowledge about chemical structure combined with limited short-term genotoxicity and toxicity test results can be used to predict potential carcinogens. Previous attempts have been potentially biased by prior knowledge about the tumorigenicity of chemicals in animals or humans, but the 44 chemicals that are currently being bioassayed for carcinogenicity by the National Toxicology Program provide an opportunity prospectively to evaluate factors that may be predictive of chemical carcinogenicity. Predictions of rodent carcinogenicity for these 44 agents are presented as an example of what we believe is the best available approach at this time. This publication will also enable others to make their own predictions (using whatever methods they believe to have high predictive value) before the results of the animal assays are known. PMID- 2184308 TI - Mutagenic DNA repair in Escherichia coli. XVII. Effect of temperature-sensitive DnaE proteins on the induction of streptomycin-resistant mutations by UV light. AB - In contrast to the dnaE486 mutation, which is nearly 'dead-stop', dnaE1026 allows DNA synthesis for some time at restrictive temperatures. When bacteria carrying the dnaE486 or dnaE1026 temperature-sensitive mutations were incubated at restrictive temperature after exposure to UV light they showed little or no fixation of mutations as determined by loss of photoreversibility and the mutation frequency fell progressively. These results confirm a role for DnaE protein (the alpha-subunit of DNA polymerase III holoenzyme) in UV mutagenesis. A derivative of dnaE1026 carrying the umuC122 allele which blocks normal UV mutagenesis showed induction of mutations when photoreversing light was given to UV-irradiated bacteria after a period of incubation at either permissive or restrictive temperature. The defective DnaE1026 protein is therefore able to carry out the misincorporations which have been postulated to be the first step in the mutagenic process. Its inability to give rise to mutations in umu+ bacteria may therefore be attributed to its inability to participate in a later step, perhaps because it is unable to interact with the UmuD, C gene products. In contrast, UV-irradiated dnaE486 umuC122 bacteria did not show mutagenesis when incubated at restrictive temperature before photoreversal, suggesting that the altered DnaE486 protein was not able to carry out the postulated misincorporation step at 43 degrees C. DNA polymerase III alpha-subunit therefore appears to be required for both the misincorporation and bypass steps in the two-step model for UV mutagenesis. PMID- 2184309 TI - Mutagenic DNA repair in Escherichia coli. XVIII. Involvement of DNA polymerase III alpha-subunit (DnaE protein) in mutagenesis after exposure to UV light. AB - UV light was unable to induce rifampicin-resistant mutations at 43 degrees C in Escherichia coli ER11 dnaE486. Although DnaE486 gene product is inactive at 43 degrees C, these bacteria contain the pcbA1 mutation which allows DNA replication provided DNA polymerase I is functional. The experiments were carried out under conditions where full expression of rifampicin-resistant mutations could occur so that the lack of induced mutations cannot be ascribed to an effect of incubation at 43 degrees C on mutation expression. UV-mutability at 43 degrees C was restored by the presence of the dnaE+ allele on a plasmid. It is concluded that functional DnaE protein is essential for UV mutagenesis. The dnaE486 mutation also blocked the induction at 43 degrees C of mutations induced by UV plus delayed photoreversal, a procedure that has been postulated to reflect an early misincorporation step in the UV mutagenic process. PMID- 2184310 TI - Genetic and biochemical analysis of glutathione-deficient mutants of Saccharomyces cerevisiae. AB - Five independently isolated glutathione-deficient (gsh-) mutants of Saccharomyces cerevisae with maximally 6% residual glutathione content have been analysed genetically. Complementation as well as tetrad analysis of the homo- and heterozygous diploids constructed by suitable crosses of the five mutants indicated that all isolates belong to one complementation group and hence represent different alleles of one gene, GSH1. In order to determine the Gsh1 gene product an assay suitable for yeast was developed to determine the activity of gamma-glutamyl-cysteine synthetase catalysing the first step of glutathione biosynthesis. All mutants are severely deficient in gamma-glutamyl-cysteine synthetase (less than 6.5% of the activity of the glutathione competent parental strain) which is in good accordance with the genetic data. PMID- 2184311 TI - Activation and detoxification of 1,8-dinitropyrene by mammalian hepatic fractions in the Salmonella mutagenicity assay. AB - 1,8-Dinitropyrene (DNP) is a potent, direct-acting mutagen to Salmonella typhimurium TA98 due to activation by bacterial metabolism. We have studied the effects of uninduced and Aroclor-induced rodent liver post-mitochondrial supernatant (S9), microsomes or cytosolic preparations on its activity. With the plate incorporation protocol, the reported S9-mediated inhibition of mutagenicity was confirmed and shown to be greater after induction when equivalent levels of protein were plated. Cytosol increased mutagenicity considerably whereas the inhibitory effect of S9 could be attributed to the microsomal fraction. The activating and detoxifying capacities of the various hepatic fractions derived from male Sprague-Dawley rats and female BALB/c mice were similar. In the absence of hepatic preparations, DNP mutagenicity was much lower in TA98/1,8DNP6 (deficient in transacetylase) than in TA98, although mutagenic activity could be still increased in the former strain by addition of uninduced cytosol. When DNP was pre-incubated in a liquid assay with S9 before addition of TA98, inhibition occurred and was time dependent. Thus the overall detoxifying effect of S9 is independent of bacterial metabolism. Furthermore, inhibition occurred under conditions where cytosol and microsomal components of S9 were kept together, indicating that the detoxifying effect of the microsomes predominates. The data therefore suggest that the microsomal-mediated detoxification by S9 may be due to the presence of an inhibitory component, enzymatic or otherwise, whose concentration is increased after Aroclor-induction. Nitro-reductase activities detected in TA98 and TA98/1,8-DNP6 were 10-fold higher than those in the mammalian fractions, although the activities in the latter increased to the bacterial enzyme levels after incubation of induced S9 or microsomes, but not cytosol, with an NADPH-generating system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2184312 TI - Strategies for optimization of short-term genotoxicity tests: the synergistic effect of NADPH and NADH on P450 function in processing pre-mutagens. AB - The synergistic effect of NADPH and NADH on P450 functions upon pre-mutagens requiring metabolism during the incubation conditions used in the liver microsomal assay (LMA) was studied. The mean specific activity (Asp) during 1 h of pre-incubation (LMA) of some microsomal mono-oxygenases (i.e. ethylmorphine N demethylase, p-nitroanisole O-demethylase and aminopyrine N-demethylase) examined with S9 fractions from sodium phenobarbital and beta-naphthoflavone pre-treated mice, was doubled when both NADPH and NADH were present. In contrast, when lipid peroxidation was used as the main enzymatic inactivation index, there was no appreciable change. In agreement with biochemical data, in vitro DNA binding of the pre-mutagenic agent [14C]-1,1,1,2-tetrachloroethane ([14C]TTCE), mediated by mouse hepatic enzymes, showed a significant enhancement (4.4-fold) of specific activity in the presence of both pyridine nucleotides. Mutagenesis experiments using TTCE in the diploid D7 strain of Saccharomyces cerevisiae (from stationary growth phase) as a biological test system, showed a significant enhancement of mitotic gene conversion and reverse point mutation frequencies when using NADPH plus NADH in the medium. Conversely, no positive results without NADH were seen. These findings lead us to suggest the routine use of both NADPH and NADH in order to increase the 'sensitivity' of in vitro mutagenicity screens. PMID- 2184313 TI - Abstracts of papers presented at the joint meeting of the United Kingdom Environmental Mutagen Society and the DNA Repair Network. Sussex, April 3-7, 1989. PMID- 2184314 TI - The third UKEMS collaborative trial. PMID- 2184315 TI - Chinese hamster ovary (CHO/HPRT) cell mutation assays with EMS, benzo[a]pyrene and benzidine. AB - In the context of the third UKEMS collaborative trial on cell mutation assays, three chemicals have been tested for mutagenicity using the Chinese hamster ovary (CHO) cell/HPRT assay. The protocol employed was based on the re-spreading of monolayer cultures, maintaining one million cells in growth for an expression time of 7 days. Ethyl methanesulphonate gave clear and consistent positive results in the absence of S9 and a clear response to benzo[a]pyrene was obtained with 1% S9. Benzidine gave no evidence of mutagenicity either with or without S9. The results show that the CHO/HPRT assay protocol used in this study is adequate for the detection of potent mutagens. The failure to detect benzidine as a mutagen may be due either to a basic unresponsiveness of the system or to a lack of sensitivity because of the limitation on the numbers of cells which can be maintained during expression. Statistical analysis showed that significant variation occurred between cell survival and mutagenicity estimates for replicate cultures, demonstrating the need for duplicate cultures. PMID- 2184316 TI - The mutagenic activity of ethylmethanesulphonate, benzidine and benzo[a]pyrene at the hprt locus of wild-type L5178Y mouse lymphoma cells. AB - Ethylmethanesulphonate (EMS), benzidine (BZD) and benzo[a]pyrene (B[a]P) were assayed for ability to induce mutation at the hprt locus of wild-type L5178Y mouse lymphoma cells. EMS was assayed in the absence of metabolic activation, B[a]P in the presence of metabolic activation (S-9 mix) and BZD both in the absence and presence of S-9. Treatment with EMS minus S-9 and B[a]P plus S-9, especially when the S-9 content of the incubation was 2% (v/v), produced strong dose-related increases in mutant frequency. BZD failed to induce mutation at the hprt locus, either in the absence or presence of S-9. PMID- 2184317 TI - Induction of mutations in mouse lymphoma L5178Y cells by ethylmethanesulphonate, benzidine and benzo[a]pyrene. AB - As part of the third UKEMS collaborative trial, the induction of mutations in mouse lymphoma L5178Y cells was analysed by an agar cloning method. The method used was based on the published methods of Clive and co-workers and Amacher and co-workers. Mutations at the thymidine kinase (tk) locus were analysed following exposure to ethylmethanesulphonate (EMS) in the absence of S9 mix, benzo[a]pyrene (B[a]P) in the presence of S9 mix and benzidine (BZD) in the absence and presence of S9 mix. Mutations were induced under all these conditions and no difference was found between a 48-h and 72-h expression period. Small and large colonies on trifluorothymidine (TFT) selective plates were expanded and found to be stably resistant to TFT. The effects of varying the S9 level and the composition of the cofactor mix on the mutagenicity of BZD and B[a]P were also analysed. The ability of BZD to induce mutations at the hprt locus was investigated. No mutations were detected either in the presence or absence of S9 mix. PMID- 2184318 TI - The third UKEMS collaborative trial. PMID- 2184319 TI - Studies on the activities of benzo[a]pyrene, benzidine and ethyl methanesulphonate in the L5178Y TK +/- mouse lymphoma mutagenicity assay using standardized and non-standardized protocols. AB - As part of the third UKEMS collaborative trial, ethylmethane sulphonate (EMS), benzo[a]pyrene (B[a]P) and benzidine (BZD) were assayed for mutagenicity using the L5178Y mouse lymphoma TK +/- forward mutation system. Exogenous metabolic activation was achieved with two different sources of rat liver S9 which were used under optimized conditions for B[a]P and BZD, the latter being tested also without S9. EMS was assayed in the absence of S9 only. Mutants were selected for trifluorothymidine (TFT) resistance after 48 and 72 h expression time. Mutant frequency (MF) data were subjected to ANOVA analysis and t-tests for differences between replicate cultures, linear trend and differences from solvent controls. Large TFT resistant colonies are believed to be due to induction of small amounts of genetic damage (point mutations, small deletions) at the tk locus, whilst small colonies are thought to be a result of larger effects. The relative proportions of the two colony types were determined in some experiments. All three compounds induced dose-related increases in MF under all conditions. B[a]P induced equal proportions of large and small colonies at all doses. EMS induced predominantly large colonies at all doses. The effect of BZD on colony size was variable. The source of S9 did not exert any consistent effect on toxicity, mutagenicity or mutant colony size. Maximum MF values occurred at 72 h for B[a]P and BZD but the results with EMS were variable. No consistent differences were apparent between estimates of toxicities made either by cloning immediately after treatment (day 0 cloning) or by estimating the relative total growth (RTG) at expression time. PMID- 2184320 TI - Microwell mutation assays: evaluation of ethylmethanesulphonate, benzo[a]pyrene and benzidine using the tk locus in L5178Y mouse lymphoma cells. AB - As part of the third UKEMS collaborative trial, ICI Central Toxicology Laboratory (CTL) tested the three study chemicals ethylmethanesulphonate (EMS), benzo[a]pyrene (B[a]P) and benzidine (BZD) in a microwell adaptation of the L5178Y gene mutation assay using the thymidine kinase (tk) locus. Cofactors for metabolic activation were optimized prior to testing the chemicals under differing expression times (48 and 72 h) and S9 levels (2,5 and 10%). The results for zero hour survival, relative total growth and mutant frequency were subjected to extensive statistical analyses. It was concluded that the methods described produce a robust and reliable assay and that for routine use a single 72 h expression time and 5% S9 level are sufficient, provided true independent replicates are used. PMID- 2184321 TI - Preparation of the S9 fraction for the third UKEMS collaborative trial. PMID- 2184322 TI - Induction of mutations in TK6 human lymphoblastoid cells by ethyl methanesulphonate, benzo[a]pyrene and benzidine. AB - The experiments described were carried out as part of the UKEMS Third Collaborative Trial. The method used was essentially that described by Thilly et al., based on a cloning assay using microtitre test plates. The induction of mutations at both the thymidine kinase (tk) locus and the hypoxanthine guanine phosphoribosyl transferase (hprt) locus was determined following exposure to ethyl methanesulphonate (EMS), benzidine (BZD) and benzo[a]pyrene (B[a]P). EMS was tested in the absence of a metabolic activation system (S9 mix), BZD was tested in the presence and absence of S9 mix and B[a]P was tested only in the presence of S9 mix. Incubation with EMS or B[a]P caused the induction of mutations at both the tk and hprt loci. The effects of benzidine were not reproducible, although some individual data points at the tk locus were found to be significant. PMID- 2184323 TI - DNA alkylations and mutation after exposure to ethyl methanesulphonate in mammalian cell lines routinely used in mutagenicity testing. AB - DNA ethylations were measured in four mammalian cell lines, Chinese hamster ovary CHO, mouse lymphoma L5178Y t k+/-, human lymphoblastoid TK6 and Chinese hamster V79, following exposure to [3H]ethyl methanesulphonate. Concurrent estimates of cytotoxicity and gene mutation were also carried out. Total DNA-binding and relative levels of ethylation at N-7 guanine (N-7G), O6 guanine (O6G) and N-3 adenine (N-3A) were essentially the same in all four cell lines. Differences in response to EMS between the cell lines, namely the greater cytotoxicity in TK6 cells, would therefore appear to reflect subsequent handling of the DNA lesions, rather than different levels of DNA ethylation in the cell lines. PMID- 2184324 TI - Determination of benzidine--DNA adduct formation in CHO, HeLa, L5178Y, TK6 and V79 cells. AB - Using 32P-postlabelling, evidence of DNA adduct formation was sought in six mammalian cell lines, namely Chinese hamster ovary (CHO), human cervical carcinoma (HeLa S3), mouse lymphoma L5178Y tk +/- and L5178Y wild-type, human lymphoblastoid TK6 and Chinese hamster V79, following treatment with benzidine (BZD) in the presence of S-9. Adduct formation was also determined in calf thymus DNA reacted in vitro with N-hydroxy-N'-acetyl-BZD, and in liver DNA from mice given a single intraperitoneal injection of BZD. DNA adducts were detected in the calf thymus DNA sample and in mouse liver DNA, but not in DNA from any of the six cell lines. The absence of adduct formation is consistent with the lack of mutagenicity of BZD in CHO, and V79 and in L5178Y cells at the hprt locus, and in TK6 cells at the tk and hprt loci. These results also suggest that the observed mutagenicity of BZD at the tk locus in L5178Y cells may be due to a mechanism(s) not involving covalent binding to DNA. PMID- 2184325 TI - Characterization of S9 fraction used in the third UKEMS collaborative trial. AB - The S9 preparation utilized by the collaborators in the third UKEMS collaborative study was assayed for the activities of three groups of enzymes and the effect of storage upon the activities. The results obtained indicate that storage of S9 at 196 degrees C for periods of up to 8 months did not unduly affect the activity of the cytochrome P450 isoenzymes measured. PMID- 2184326 TI - A statistical analysis of the third UKEMS collaborative trial. AB - In the third UKEMS collaborative trial, nine laboratories optimized protocols for a variety of mammalian cell mutagenicity assays and used these protocols to test three reference mutagens. Data from the trial have been deposited with Mutagenesis under the scheme of the journal for a database of results of extensive mutagenicity testing programmes. A preliminary examination of the data using procedures advocated by the UKEMS guidelines on statistical evaluation of mutagenicity test data confirms that the assays are capable of giving clear, convincing data, in a form amenable to statistical analysis. The utility of the methods of analysis proposed by both the plate and fluctuation test statistical working groups was confirmed. In almost all cases variation between plates or trays from the same replicate treatment was little greater than Poisson or binomial, whereas variation between replicate treatments was substantially larger, confirming the recommendation of both groups for true independent replicates of each treatment. In six out of nine laboratories part of this variation between replicates was consistent for both viability and mutation, which might cause the guide-lines procedure for fluctuation test data to underestimate significance. In about half the cases examined, variation between experiments was significantly greater than variation between replicates within an experiment, which may create problems of interpretation. Supplementary tests, using the statistical package GLIM, suggested that although factors such as choice of expression time, level of S9, zero dose cloning efficiency or spontaneous mutation frequency might have an effect, they would not have been likely to interfere with detection of a mutagenic effect in the present data set. PMID- 2184327 TI - The third United Kingdom Environmental Mutagen Society collaborative trial: overview, a summary and assessment. AB - An overview of the results of the third UKEMS collaborative trial with cultured mammalian cells is presented and their implications are discussed. Data suitable for statistical evaluation are generated by using the protocols which have been developed for the trial. The results for the three test compounds, ethyl methane sulphonate, benzo[a]pyrene and benzidine (BZD) from the nine participating laboratories demonstrated the essential requirement for replicate cultures in any adequate experimental design. Amongst the many practical points that are reinforced by this study are: (i) the number of cells to be sub-cultured during expression imposes a severe limitation on the use of surface attached cells; (ii) the importance of a careful determination of toxicity; (iii) that S9 levels may need to be varied; and (iv) that BZD is mutagenic only at the tk locus in L5178Y TK+/- cells. The 32P-post-labelling study with BZD reveals that no detectable DNA adducts were found with this agent even in L5178Y or HeLa cells. Thus the mechanism for mutagenesis in L5178Y cells remains to be elucidated. PMID- 2184328 TI - Mutation assays of ethyl methanesulphonate, benzidine and benzo[a]pyrene using Chinese hamster V79 cells. AB - As a contribution to the third UKEMS collaborative trial, ethyl methanesulphonate (EMS), benzo[a]pyrene (B[a]P) and benzidine (BZD) were examined for mutagenicity at the hprt locus in Chinese hamster V79 cells, as assessed by 6-thioguanine (6TG) resistance. EMS was examined in the absence of any exogenous metabolic activation system, and the mutagenic dose-response obtained served to calibrate the assay. B[a]P and BZD were examined using three levels of Aroclor 1254-induced rat liver S9 supplemented with standardized concentrations of cofactors for NADPH generation. B[a]P showed S9 mediated cytotoxicity and mutagenicity, with the magnitude of both responses decreasing with increasing amounts of S9. No evidence of mutagenicity was seen for BZD with any of the metabolic activation conditions employed. PMID- 2184329 TI - Infection after joint replacement--what would Lister think? PMID- 2184330 TI - Protection against recurrent acute bronchitis after oral immunization with killed Haemophilus influenzae. AB - Subjects prone to recurrent acute bronchitis were admitted to a six-month double blind clinical study, in which the value of oral immunization with a preparation of killed Haemophilus influenzae was tested. Most subjects had early smoking related chronic lung disease, unrecognized by either the patient or his/her doctor. Subjects taking the active agent had a 41% reduction in the total number of episodes of acute bronchitis (P = 0.16), a 60% reduction in the number of episodes of acute wheezy bronchitis (P = 0.02) and a 58% reduction in antibiotic use (P = 0.07). The power of analysis was restricted by the small study group. Parameters of episode severity favoured the test group, suggesting that individual episodes of acute bronchitis in subjects taking an oral preparation of killed H. influenzae were less severe than in those taking placebo tablets. Oral immunization with H. influenzae selectively reduced the increase in colonization of the oropharynx with H. influenzae which occurred in the group taking placebo. This is the first demonstration that the common mucosal system can be activated to modify a colonization pattern at a distant site. PMID- 2184331 TI - Update in the management of prostate cancer. AB - Prostate cancer remains one of the commonest malignancies in our community, and it appears that its incidence is rising because of the increasing proportion of the aged population. Improved technology, including the development of new tumour markers and tumour imaging techniques, and a gradually increasing community awareness of this disease, may allow earlier diagnosis. In turn, as the proportion of patients presenting with early stage disease increases, improved approaches to the treatment of localized cancer may thus yield increased community cure rates. The mainstay of treatment of advanced disease remains hormonal manipulation. The introduction of the LHRH agonists has provided an alternative to surgical castration, but has not resulted in an improved response rate or survival from first-line therapy. We believe that these agents do not offer a major benefit, when compared with the simple procedure of orchidectomy, notwithstanding the psychological sequelae of castration. With a median survival of less than five years after hormonal manipulation, many patients still require salvage treatment after relapse. New hormonal therapies yield objective and subjective response rates of approximately 15% and 30%, respectively, but the median survival from the time of hormonal failure remains less than one year. Cytotoxic chemotherapy has not provided a panacea, but has shown definite evidence of antitumour activity in this disease. The use of relatively non-toxic single cytotoxic drugs can provide effective palliation of symptoms in up to 40% of patients and may even prolong survival in some patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2184332 TI - A place for surgery in arthritic diseases. PMID- 2184333 TI - Calcium and osteoporosis. PMID- 2184334 TI - Extended broad-spectrum beta-lactamases in Australia. PMID- 2184335 TI - [Hypertension, diabetes mellitus and obesity]. PMID- 2184336 TI - [Drug administration. References for storage and packaging]. PMID- 2184337 TI - Antibodies to recombinant HIV-1 vif, tat, and nef proteins in human sera. AB - The prevalence of antibodies against HIV-1 regulatory proteins in sera of HIV infected patients from different stages of disease was investigated. HIV-1 vif, tat, and nef genes were cloned in procaryotic vectors and were expressed as MS-2 fusion proteins (vif and nef) or as a non-fusion protein (tat). These recombinant proteins were employed in immunoblot experiments. The specificity of the recognition was confirmed by competition experiments and with control sera from HIV-negative patients. Analysis of 136 serum samples revealed a high percentage of antibodies against nef, irrespective of the stage of disease. Antibodies against tat were found less frequently and increased from 16% to 40% with disease progression. Vif antibodies were detected only in a low percentage in early stages of disease, but their prevalence increased to 36% and 72% with progression of disease to AIDS-related complex and AIDS. Our data suggest that the detection of antibodies against nef may represent an additional and useful marker for the diagnosis of HIV infection, whereas the detection of vif antibodies may indicate disease progression. PMID- 2184338 TI - Immunopathological investigations during the course of arthritis induced in rats by Streptococcus agalactiae. AB - A large single intraperitoneal injection of sonicated cells of Streptococcus agalactiae O90R induced polyarthritis in Wistar rats. The arthritis reaction score was monitored according to redness, edema, severity and deformity of rat ankle and wrist joints. The inflammation of joints was confirmed by radiology and histology. Acute arthritis was initiated within 48 h and the chronic form continued for more than 30 days. Although serum immunoglobulin was elevated within 48 h, anti-streptococcal antibody was detected only at later times (by enzyme-linked immunosorbent assay and Arthus-type hypersensitivity reactions) and neither serum nor splenocytes of arthritic rats were able to transfer disease to susceptible, normal rats. From these observations and the finding of streptococcal antigen in joint macrophages (by immunogold labelling) we conclude that arthritis is related to persistent streptococcal fragments rather than to antibody or immune complexes. PMID- 2184339 TI - Screening media for detection of methicillin-resistant Staphylococcus aureus from non-sterile body sites. AB - Four hundred and forty clinical isolates were tested on Baird-Parker and Vogel Johnson agars with 6 micrograms/ml of oxacillin, to determine their growth characteristics on these potential screening media for methicillin-resistant Staphylococcus aureus (MRSA). While both media performed well individually, a combination biplate with each medium may be the most useful in screening patients for MRSA from normally non-sterile sites. PMID- 2184340 TI - Klinefelter's syndrome and primary central nervous system lymphoma. AB - Klinefelter's syndrome is known to be associated with various malignancies including male breast cancer and germ cell tumour. We report a patient with Klinefelter's syndrome who developed a primary B-cell lymphoma of the central nervous system (CNS). To the best of our knowledge, this is the first case of primary CNS lymphoma in Klinefelter's syndrome. PMID- 2184341 TI - Brain tumor as a second malignant neoplasm following neuroblastoma stage IV S. AB - A rare brain tumor (spongioblastoma polare) occurring 7 years after treatment of neuroblastoma stage IV S is reported. The literature concerning the occurrence of a second cancer in children exposed to mutagenic therapy for their initial tumor is reviewed, and genetic and environmental factors are discussed. Diminishing aggressiveness of the treatment in childhood cancer with good prognosis should be considered. Continuous follow-up of children cured of cancer is warranted. PMID- 2184342 TI - [Beta-thalassemia and its orodental implications. I. The clinical considerations]. AB - The paper reviews the literature on oral modifications presented by subjects affected by beta-thalassemia, an hereditary hemopathy present in significant numbers in some areas of Italy. Following a description of the clinical characteristics of the disease, the paper focuses on the genetic alterations leading to the hemopathy and their implication in the onset of the thalassemic state. PMID- 2184343 TI - [Otorhinological evaluations of patients undergoing rapid disjunction of the median palatine suture]. AB - Seven young patients, who had been diagnosed to be oral breathers by an orthodontist, have been submitted to an ETN specialist examination, before and after the rapid expansion of the mid-palatal suture. Five of these patients had an actual reduction of nasal breathing capacity. Four patients presented a significant enlargement of the adenoids. One patient showed a transmission auditive deficiency. The ETN examination, two months after the maxillary expansion, has permitted to find out that all the patients who had an impaired nasal breathing before the maxillary expansion, had normalized their respiratory capacity. Moreover, those subjects who had enlarged adenoids, showed a normal adenoids volume in the second ETN examination. Finally also the patient with an auditive deficiency presented a normalization of this function at the second ETN examination. PMID- 2184344 TI - [Periodontal therapy. I. The working philosophies]. AB - Periodontal treatment has recently been evaluated by numerous research projects which have confirmed its validity and clarified the indications and limits of treatment. In this review the authors discuss and analyse the results achieved using different techniques of periodontal therapy; moreover, attention is focused on the apparent similarity of results obtained using conservative and surgical methodologies. PMID- 2184345 TI - Nurse education and convergent information technologies. AB - This article concerns one of the main problems facing nurse education, that of meeting individualised learner needs. This endeavour is inescapable because of current trends in the curriculum, trends towards continuous assessment and more recently, advice from the English National Board (ENB) regarding continuous theoretical assessment. Computer assisted learning, it is suggested, can be helpful in nurturing individual learner progress. Sophisticated technologies are available to educationalists which develop individual learning strategies, but the cost of producing the necessary courseware is high, both in terms of money and tutor time. Hopefully a solution has been found as a project has been funded and is being run by the ENB allowing tutors to develop skills in this area of education. PMID- 2184346 TI - Immunofluorescence localization of the regulatory subunit type II of cAMP dependent protein kinase in PC12 and 3T3 cells in different proliferative states. AB - Localization of the regulatory subunit of cAMP-dependent protein kinase type II was studied in proliferating and quiescent fibroblasts 3T3 and in a cell line of neural origin pheochromocytoma PC12. In actively proliferating PC12 cells the regulatory subunit was found to be localized in the nucleus. Transition of these cells into a quiescent state was accompanied by a regulatory subunit translocation to the cytoplasm. In 3T3 cells the regulatory subunit was localized in the cytoplasm both in the quiescent and proliferating (though less actively than PC12 cells) states. Similar results were obtained both with monoclonal antibodies and with rabbit monospecific antiserum raised against the regulatory subunit type II from pig brain. PMID- 2184347 TI - Effects of phospholipases, proteases and neuraminidase on gamma-hydroxybutyrate binding sites. AB - gamma-Hydroxybutyric acid (GHB) is a natural compound of mammalian brain synthesized from GABA. The characteristics of its synthesis, transport, release, distribution and turnover, in addition to the presence of a high affinity binding site for this substance in brain are in favor of a modulator role for GHB. The effects of hydrolytic enzymes on the specific binding capacity of GHB have been studied in the present work. Phospholipases A2 and C, neuraminidase and Pronase markedly decrease GHB binding to crude synaptosomal membranes from rat brain. This effect is time and enzyme concentration dependent. Trypsin, under the conditions employed, is less active. The inhibitory effects of phospholipases is correlated with phospholipid hydrolysis. Lysophospholipids, in the absence of bovine fatty acid free serum albumin partially inhibit GHB binding. The action of neuraminidase has been followed by sialic acid release and modifications of the ganglioside profile. The effects of phospholipase C and of neuraminidase are completely different to those on GABA binding sites. These results represent further data concerning the molecular existence of specific GHB binding sites on rat brain membranes. PMID- 2184348 TI - A role for DNA methylation in vertebrate gene expression? PMID- 2184349 TI - Mutation of tyrosine residues 1162 and 1163 of the insulin receptor affects hormone and receptor internalization. AB - Insulin internalization and degradation, insulin receptor internalization and recycling, as well as long term receptor down-regulation were comparatively studied in Chinese hamster ovary (CHO) cell lines, either parental or expressing the wild-type human insulin receptor (CHO.R) or a mutated receptor in which the tyrosine residues in positions 1162 and 1163 were replaced by phenylalanines (CHO.Y2). The two transfected cell lines presented very similar binding characteristics, and their pulse labeling with [35S]methionine revealed that the receptors were processed normally. As expected, the mutation of these twin tyrosines resulted in a defective insulin stimulation of both receptor kinase activity and glycogen synthesis. We now present evidence that compared to CHO.R cells, which efficiently internalized and degraded insulin, CHO.Y2 cells exhibited a marked defect in hormone internalization, leading to impaired insulin degradation. Moreover, the mutated receptors were found to be less effective than the wild-type receptors in transducing the hormone signal for receptor internalization, whereas the process of receptor recycling after internalization seemed not to be altered. In parental CHO cells, insulin induced long term receptor down-regulation, but was totally ineffective in both transfected cell lines. These results reveal that the tyrosines 1162 and 1163 in the kinase regulatory domain of the receptor beta-subunit play a pivotal role in insulin and receptor internalization. PMID- 2184350 TI - Cellular mechanisms of tumor rejection in rats. AB - The mechanisms of tumor rejection by cell-mediated immunity were reviewed in a rat autochthonous and syngeneic tumor-host system. The immune system could mediate a complete regression of autochthonous tumor if the tumor cells were immunogenic. Neutrophils and macrophages first appeared following transplantation of autochthonous tumor. Lymphocytes increased in the tumor tissue as the tumor began to show regression. Degenerated tumor tissue was infiltrated by macrophages and plasma cells. The identification of rat hematopoietic cells including various subsets of lymphocytes and inflammatory cells became possible owing to a variety of monoclonal antibodies reacting with these cells. Major populations of tumor infiltrating lymphocytes (TIL) were found to be R1-3B3 (CD5)- and R1-10B5 (CD8) positive cells in methylcholanthrene-induced autochthonous tumor. These CD5- and CD8-positive lymphocytes were also recognized in an N-nitrosourea-induced syngeneic tumor-host system and actually showed specific cytotoxicity against tumor cells in vitro. Macrophages were recognized in tumor tissues more predominantly in the early and terminal phase of tumor rejection; their functions are still uncertain but they are considered to have important immunomodulatory effects. A variety of cytokines were thought to play an important role in augmenting host immunity to achieve tumor rejection. Neutrophils in the tumor tissue were shown to produce a factor attracting lymphocytes to the tumor site, which was designated as lymphocyte migration factor. Subsequently, activities of colony-stimulating factor, interleukin-1, -2, and -3, and cytotoxic-T-cell generating factor (CGF), which induces final maturation of cytotoxic T cells, were detected at the tumor site as well as in the regional lymph nodes and the spleen. CGF was found to be produced by W3/25 (CD4)-positive T cells. Lymphocytes residing in the spleen of the immune rats did not show cytotoxic activity against tumor cells but significant tumor lysis activity was recognized with TIL. This suggests that lymphocytes may achieve maturation after they leave the spleen. Cellular reactions occurring at the tumor site were enhanced at each step by various cytokines produced by lymphocytes as well as by inflammatory cells. This cytokine cascade seems to be essential for obtaining a sufficient immune response for tumor rejection. When an established T9 subcutaneous tumor with a diameter of 10 mm was treated by intratumoral infusion of lymphokine-activated killer (LAK) cells, the tumor showed complete regression after 2-3 weeks of transient growing.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2184351 TI - Hypothalamic control of the generation of mature natural killer lymphocytes in bone marrow and spleen of the mouse. AB - Following previous work showing that electrothermocoagulation of the median region of the hypothalamus (MH) caused a marked and permanent decrease in the cytotoxicity of natural killer (NK) cells and in the number of large granular lymphocytes, a study was made of the effect of such lesions on the generation of NK cells in the bone marrow (BM) and spleen of C57BL/6 mice. Fresh spleen and BM cells from MH-lesioned and sham-operated mice were cultured with 40 U of recombinant interleukin-2 (rIL-2). NK activity was significantly higher in BM of lesioned mice, whereas spleen NK activity was greater in the sham-operated controls. NK cells matured by culture with rIL-2 were characterized by assay with fluorescent monoclonal antibodies and found to display the typical NK phenotype. These results show that the number of NK precursors is greater in BM of MH lesioned mice and that their migration into other organs is probably partially impeded. It can also be concluded that intactness of both BM and the hypothalamus is essential for the physiological generation of NK cells. PMID- 2184352 TI - Occurrence of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-6 methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and other heterocyclic amine mutagens in oil of charred egg yolk (ranyu). AB - Mutagenicity of oil of charred egg yolk (called ranyu in Japanese), which is commercially available and consumed as a health food in Japan, was tested on Salmonella typhimurium strains TA98 and TA100 with and without metabolic activation. Both strains showed a high response to the oil, and the number of His+ revertant colonies with strain TA98 was 15,000-20,000 for 1 g equivalent amount of oil. The mutagens were purified by acid extraction, chloroform extraction after alkalization, dialysis, adsorption to blue cotton, passing through a Sephadex LH-20 column and several stages of high-pressure liquid chromatography with reverse-phase columns. At least 7 heterocyclic amine mutagens were detected. Two of them were suggested to be 2-amino-3-methylimidazo[4,5 f]quinoline (IQ) and 2-amino-6-methyldipyrido [1,2-a:3',2'-d]imidazole (Glu-P-1). One was suggested to be 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ). The others were not identified but distinguishable from 12 known heterocyclic amine mutagens. The estimated minimum contents of IQ and Glu-P-1 were 1.1 ng/g and 4.8 ng/g, respectively. PMID- 2184353 TI - Mutagenicity of isoquinoline alkaloids, especially of the aporphine type. AB - The mutagenicity of 44 isoquinoline alkaloids was tested in Salmonella typhimurium TA100 and TA98 in the presence or absence of S9 mix. The alkaloids tested included compounds from the isoquinoline, benzylisoquinoline, bisbenzylisoquinoline, monoterpene isoquinoline, berberine, morphinane, hasubanan, benzo[c]phenanthridine and aporphine groups. Among the alkaloids tested, liriodenine was the most potent mutagen for TA100 and roemerine was the most potent for TA98. A clear structure-mutagenicity relationship was observed in a series of aporphine alkaloids (aporphine, dehydroaporphine, 7-oxoaporphine and 4,5-dioxoaporphine), and 10,11-non-substituted aporphines were suggested to exert their mutagenicity through metabolic activation of the 10,11 positions, possibly as the 10,11-epoxides. PMID- 2184354 TI - Genetic toxicity of the benzene metabolite trans, trans-muconaldehyde in mammalian and bacterial cells. AB - Previous studies in our laboratory identified trans,trans-muconaldehyde (MUC), a six-carbon diene dialdehyde, as a microsomal metabolite of benzene. This ring opened metabolite of benzene was also shown to be hematotoxic in mice in a manner similar to benzene. To further explore the role of MUC in relation to benzene toxicity, a number of test systems were utilized to determine its genotoxic potential. In B6C3F1 mice, MUC induced a highly significant increase in sister chromatid exchange (SCE), the lowest effective dose being 3 mg/kg, but failed to induce any micronuclei (MN). In Chinese hamster ovary (CHO) cells, MUC at concentrations up to 0.8 micrograms/ml was negative in the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) assay. Dose-related increases in the percentage of cells with MN were observed in CHO cells treated with 0.4-0.8 micrograms/ml MUC. MUC did not-cause unscheduled DNA synthesis in rat primary hepatocytes. Treatment of Salmonella typhimurium TA97 with MUC induced a low level of mutations at concentrations ranging from 10 to 70 micrograms/ml with or without S9 activation. MUC was inactive in strains TA1535, TA100, TA1538 and TA98. In CHO cells and rat primary hepatocytes, MUC was cytotoxic at 0.4 and 4.0 micrograms/ml, respectively. Concentrations of 100 micrograms/plate MUC were toxic for bacterial cells. The present findings indicate that MUC is nonmutagenic or minimally mutagenic in bacterial and mammalian in vitro systems. In mammalian cells, MUC is highly cytotoxic and genotoxic. PMID- 2184355 TI - A controlled trial of cyclosporine in the treatment of primary biliary cirrhosis. AB - Primary biliary cirrhosis is a progressive disease of the liver characterized by the immunologic destruction of bile ducts; effective therapy is lacking. We therefore evaluated the safety and efficacy of low-dose cyclosporine in 29 patients with primary biliary cirrhosis without evidence of damage to the lobular architecture (precirrhotic disease) or portal hypertension. The patients were randomly assigned to receive either cyclosporine (4 mg per kilogram of body weight per day) or placebo. After one year 17 of the 19 patients assigned to cyclosporine had improvement or stability in their degree of fatigue, and 18 in their degree of pruritus. In contrast, among the 10 patients assigned to placebo, fatigue increased in 4 (P less than 0.06) and pruritus worsened in 6 (P less than 0.001). Those assigned to cyclosporine also had significant decreases in serum levels of bilirubin, alanine aminotransferase, alkaline phosphatase, gamma globulin, and the titer of antimitochondrial antibodies. For the 20 patients who have completed two years in the study, liver biopsies (coded specimens) showed evidence of histologic progression in only 1 of 13 patients in the cyclosporine group, as compared with 5 of 7 in the placebo group (P less than 0.003). No patient has permanently discontinued cyclosporine because of side effects; however, signs of nephrotoxicity developed in 12 of 19, and 9 of 19 had increased blood pressure. We conclude that in patients with precirrhotic primary biliary cirrhosis, immunosuppressive therapy with cyclosporine is promising and deserves further evaluation. PMID- 2184356 TI - Maintenance treatment with recombinant interferon alfa-2b in patients with multiple myeloma responding to conventional induction chemotherapy. AB - The use of interferon for the induction treatment of multiple myeloma has been shown to be effective in about 20 percent of patients. We studied its effects on long-term survival when it was used for maintenance treatment. Between April 1985 and May 1988, 101 patients with symptomatic multiple myeloma who had had a substantial objective response or a lesser objective response with disappearance of symptoms ("disease stabilization") after 12 courses of induction chemotherapy were randomly assigned to receive recombinant interferon alfa-2b as maintenance therapy (n = 50) or to receive no treatment (n = 51). As of December 1989, 66 of the 101 patients have relapsed (25 given interferon and 41 not treated). The median duration of response (from the time of randomization) was 26 months in the patients given interferon and 14 months in the untreated patients (P = 0.0002). A total of 37 patients have died (14 given interferon and 23 not treated). The median duration of survival (from randomization) was 52 months in the interferon group and 39 months in the control group (P = 0.0526). Among the patients who had had a substantial objective response to induction chemotherapy, the difference in survival time was statistically significant (P = 0.03526). Interferon had to be stopped because of toxic effects in 3 of 12 patients initially treated with 10 MU (megaunits) per square meter of body-surface area. After the dose was reduced to 3 MU per square meter, the only toxic effect was a mild influenza-like syndrome lasting two to three weeks. We conclude that maintenance treatment with interferon prolongs response and survival in patients with multiple myeloma who have responded to conventional induction chemotherapy. PMID- 2184357 TI - Nazi science--the Dachau hypothermia experiments. PMID- 2184358 TI - Geriatrics: gait disorders in the elderly. PMID- 2184359 TI - Treatment of spinal-cord injury. PMID- 2184360 TI - The Nazi hypothermia experiments and unethical research today. PMID- 2184361 TI - Health care reform--why so slow? PMID- 2184362 TI - RU-486 abortion drug. Back-door trial for US? PMID- 2184363 TI - When is a drug 'safe'? PMID- 2184364 TI - Immunology. Some savage cuts in defence. PMID- 2184365 TI - Glucose in glucagon release. PMID- 2184366 TI - DNA supercoiling and environmental regulation of virulence gene expression in Shigella flexneri. AB - Bacterial pathogens undergo profound physiological changes when they infect their hosts, requiring coordinated regulation of gene expression in response to the stresses encountered during infection. A number of environmental stresses (such as osmotic shock and anaerobiosis) have been shown to induce changes in DNA supercoiling that can directly affect the transcription of a specific subset of bacterial genes, at least some of which (the outer-membrane porins and type 1 fimbriae) play a part in bacterial virulence. Here, we demonstrate that the virR gene of S. flexneri, implicated in the temperature regulation of plasmid-encoded virulence genes, is equivalent to the osmZ gene of Escherichia coli, which has previously been shown to mediate its regulatory effects through changes in DNA supercoiling. Our results imply that environmentally induced changes in DNA supercoiling are important in the coordinated control of virulence gene expression in S. flexneri and have general implications for the control of bacterial virulence. PMID- 2184367 TI - DNA mutagenesis and recombination. AB - The polymerase chain reaction is used for site-specific mutagenesis and for DNA recombination without any enzymatic reaction in vitro, apart from DNA amplification. PMID- 2184368 TI - Cold shock and DNA binding. PMID- 2184369 TI - Induction of CD8+ cytotoxic T cells by immunization with purified HIV-1 envelope protein in ISCOMs. AB - To reduce the risks of immunization with killed or live attenuated virus vaccines, it may be advantageous to use a pure, defined antigen that contains determinants for both humoral and cellular immunity. However, although most non living intact protein preparations induce antibodies and CD4+ major histocompatibility complex (MHC) class II-restricted helper and/or cytotoxic T lymphocytes (CTL), they do not elicit CD8+ MHC class I restricted CTL. Indeed, with a few exceptions, it has not so far been possible to induce CD8+ CTL by immunizing with intact soluble proteins. We show here that a single subcutaneous immunization in mice with immunostimulating complexes containing either purified intact gp160 envelope glycoprotein of the human immunodeficiency virus (HIV)-1 or influenza haemagglutinin results in reproducible and long-lasting priming of HIV specific or influenza-specific CD8+, MHC class I restricted CTL. PMID- 2184370 TI - Autoimmune response in AIDS. PMID- 2184371 TI - Data case turns ugly. PMID- 2184372 TI - Tat protein of HIV-1 stimulates growth of cells derived from Kaposi's sarcoma lesions of AIDS patients. AB - Kaposi's sarcoma (KS) is frequently associated with human immunodeficiency virus 1 (HIV-1) infection. Supernatants from HIV-1-infected T cells carrying the CD4 antigen promote the growth of cells derived from KS lesions of AIDS patients (AIDS-KS cells), and the HIV-1 tat gene, introduced into the germ line of mice, induces skin lesions closely resembling KS. Here we report that the tat gene product (Tat) is released from both HIV-1-acutely infected H9 cells and tat transfected COS-1 cells. These Tat-containing supernatants specifically promote growth of AIDS-KS cells which are inhibited by anti-Tat antibodies; recombinant Tat has the same growth-promoting properties. Therefore a viral regulatory gene product can be released as a biologically active protein and directly act as a growth stimulator. These and previous data indicate that extracellular Tat could be involved in the development or progression, or both, of KS in HIV-1-infected individuals. PMID- 2184373 TI - Overhauling Medicare's quality assurance program. PMID- 2184374 TI - An interview with Stuart H. Altman and Uwe E. Reinhardt. Interview by Carmella Bocchino. PMID- 2184375 TI - Cholecystokinin octapeptide potentiates the inhibitory response mediated by D2 dopamine receptors in slices of the ventral tegmental area of the brain in the rat. AB - The ability of cholecystokinin octapeptide (CCK8) to modulate dopamine (DA) induced inhibition of the firing of neurons in the ventral tegmental area of the rat was examined. Extracellular recordings were obtained from putative DA containing neurons, identified on the basis of their electrophysiological characteristics and response to DA, in an in vitro slice preparation from the ventral tegmental area of the brain. Application of DA produced a concentration dependent reduction in firing rate. This DA-induced inhibition was mimicked by the D2 selective agonist, LY 171555 (trans-(-)-4,4a,5,6,7,8,8a,9-octahydro-5 propyl-2H- pyrazolo[3,4-g]quinoline), but not by the D1 selective agonist, SKF 38393 (R-(+)-2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine). The DA induced inhibition was antagonized selectively by the D2 antagonist, l-sulpiride, but not by the D1 antagonist, SCH 23390 (R-(+)-8-chloro-2,3,4,5-tetrahydro-3 methyl-5-phenyl-1H-3-benzazepine-7- ol). However, CCK8 elicited a transient increase in firing rate in some neurons and, in addition, potentiated the inhibitory response evoked by DA or LY 171555. Again SKF 38393 was without effect following the administration of CCK8. Taken together, these results suggest that DA-induced inhibition of DA-containing neurons in the ventral tegmental area of the brain of the rat is mediated by activation of D2-receptors and that CCK8 potentiates this D2-mediated inhibition. PMID- 2184376 TI - Efficacy and potency comparisons among aporphine enantiomers: effects on dopamine neurons in substantia nigra of rat. AB - Extracellular single unit recording studies were carried out on male rats to determine the responses of dopamine neurons of the substantia nigra to intravenous administration of the enantiomers of the aporphine congeners, apomorphine (APO), N-n-propylnorapomorphine (NPA) and 11-hydroxy-N-n propylnorapomorphine (11-OH-NPa). The R-(-)-configuration was found to be the most critical determinant of the efficacy and potency of the agonists. All R-(-) aporphines were full agonists, able to inhibit completely firing of dopamine cells. The order of potencies, defined by the ID50s, was: (-)NPA, 2.0 +/- 0.4 nmol/kg greater than (-)11-OH-NPa, 4.7 +/- 0.7 nmol/kg greater than (-)APO, 18.0 +/- 4.0 nmol/kg. Thus, potency was increased about 9-fold by replacing the 6N methyl of APO with an n-propyl (NPA). Conversely, the 10-hydroxy was not essential for agonist activity (11-OH-NPa) but could increase potency. In the S (+)-series responses varied. (+)N-n-Propylnorapomorphine exhibited agonist properties and could fully inhibit dopamine cells, but its potency was low (ID50 1550 nmol/kg); (+)APO produced only slight but significant decreases in firing at large (8434 nmol/kg) doses and (+)11-OH-NPa was devoid of efficacy in that it caused no significant changes in firing. Despite their loss of efficacy and potency, the (+)-enantiomers apparently did retain affinity for DA receptors, since they could act as antagonists if given before (-)APO or NPA. These findings suggest that stereochemical conformation and key structural elements of the aporphines are interactive in determining agonist efficacy and potency within this physiological test system. PMID- 2184377 TI - Rudimentary cephalocele or neural crest remnant? AB - Three cases of the so-called rudimentary cranial meningocele/encephalocele are presented. A review of the literature yielded a number of similar cases which were tabulated and analyzed. It is suggested that this group of lesions represents neural crest remnants for which there is a good prognosis, distinct from the true meningocele/encephalocele complex. PMID- 2184378 TI - Suprasellar ectopic pituitary adenoma: case report and review of the literature. AB - The occurrence of a totally suprasellar ectopic pituitary adenoma in a 71-year old man is described. The tumor was attached to the pituitary stalk, extending upward toward the third ventricle. No intrasellar lesion was observed. Histological examination revealed a pituitary adenoma with large numbers of eosinophilic cells with moderate nuclear polymorphism and rare mitosis. Immunohistochemical staining revealed that the tumor cells were strongly positive for anti-adrenocorticotropic hormone antibody. A review of five previously reported intracranial ectopic pituitary adenomas revealed that two were silent corticotropic tumors and two occurred with Cushing's syndrome. PMID- 2184379 TI - Giant aneurysm of the pericallosal artery. AB - A rare case of a giant aneurysm of the pericallosal artery, evaluated by computed tomography, magnetic resonance imaging, and angiography, is reported, and the other 7 cases in the literature are reviewed. Giant aneurysms are exceptional in the distal segments of the anterior cerebral arteries, and may simulate a callosal tumor or hematoma on computed tomographic scan. The clinical, radiological, surgical, and pathological findings of giant aneurysms of this location are discussed and the other reported cases are analyzed. The role of magnetic resonance imaging in diagnosing and characterizing giant aneurysms is stressed. PMID- 2184380 TI - Clinical neuromythology VII. Artificial intelligence: the brain transplant cure for parkinsonism. PMID- 2184381 TI - Benign autosomal dominant syndrome of neuronal Charcot-Marie-Tooth disease, ptosis, parkinsonism, and dementia. AB - We present a kindred with a previously undescribed combination of neuronal Charcot-Marie-Tooth disease, ptosis, parkinsonism, and mild dementia. The propositus, a 72-year-old man, had pes cavus, peripheral neuropathy, ptosis, parkinsonism, hyperreflexia, orthostatic hypotension, central hypoventilation, and mild dementia. Peripheral electrophysiologic studies showed features of an axonal neuropathy. The electroencephalogram showed intermittent 2 to 4 Hz activity symmetrically in the hemispheres. Several family members in 3 generations had pes cavus, neuropathy, ptosis, parkinsonism, and dementia although not all of the features were consistently present. Survival past the 7th decade was common. Autopsy in 2 affected members revealed the neuropathy to be axonal in type and showed mild to moderate loss of anterior horn cells in the spinal cord and pigmentary loss with gliosis in the substantia nigra. This is a unique, benign, autosomal dominant syndrome which shows complete penetrance, variable expression, and both central and peripheral nervous system involvement. PMID- 2184382 TI - Neurectasy: the short history of therapeutic nerve stretching and suspension. PMID- 2184383 TI - Nightingale's perspective of nursing administration. AB - Nightingale is often thought of for her clinical nursing care, but Henry, Woods, and Nagelkerk remind us that she was first and foremost a nursing administrator. Much of Nightingale's advice, as quoted here, sounds strangely modern and applicable today. PMID- 2184384 TI - A nursing department can and should plan for the future. PMID- 2184385 TI - The memorial oration. PMID- 2184386 TI - Delphi forecasting as a planning tool. PMID- 2184387 TI - New Medicare rates for ambulatory surgery. PMID- 2184388 TI - A comparison of the wound integrity produced by various suture patterns in penetrating keratoplasty: a cadaver eye model. AB - We tested the watertightness of wound closure in penetrating keratoplasty as a function of suture pattern by performing a 7.5-mm penetrating keratoplasty on 12 human cadaver eyes using a variety of suture patterns. We then tested wound integrity by hydrostatically raising the intraocular pressure. In this cadaver eye model, we demonstrated that running sutures produced better wound closure than interrupted sutures using the same number of bites. A 16-bite running or a combined running-interrupted pattern produced more than ample watertightness in penetrating keratoplasty wound closure. PMID- 2184389 TI - An evaluation of techniques for measuring stereopsis in infants and young children. AB - Demonstrating stereopsis is valuable in vision screening of infants and toddlers, since its presence rules out the possibility of profound visual deficits. We assessed the performance of 55 infants and young children on three clinically available tests, the Lang, the Frisby and the TNO. The results were compared with those found using a computerized dynamic random dot stereogram. Most of the children tested were under 3 years of age and 10 were aged under 1 year. The Lang test was passed by 74%, including 50% of those under 1 year. The Frisby test was passed by 65%, but by only 20% of infants under 1 year. Forty-nine per cent passed the TNO test; none were under 1 year. The computerized stereogram was passed by 42.5% of those tested, including 100% of those over 3 years old. Both this test and the TNO presented difficulty in testing infants between 8 months and 2 years because of the increased likelihood that these children would reject the red/green glasses. We recommend that the most appropriate stereotest is largely based on whether the child will tolerate red/green glasses. We would use the dynamic random dot test for infants under 8 months of age, the Lang or Frisby stereotest for infants from 8 months to 30 months, and the TNO or dynamic random dot stereogram after this age. PMID- 2184390 TI - The role of closed reduction in tibial shaft fractures. AB - Although several methods of treating difficult tibial shaft fractures have been introduced in the past few decades, closed reduction remains the cornerstone of treatment. The physician must be able to recognize those tibial fractures suitable for treatment by this method, as opposed to fractures that have the potential to cause problems and would be better handled initially by other means. Properly performed, closed reduction in conjunction with early weight bearing accomplishes the goals of solid bony union, normal function, and a cosmetically acceptable appearance. This nonoperative approach avoids the potential morbidity associated with surgery and has been shown to give excellent results in the hands of a number of different physicians. PMID- 2184391 TI - The treatment of open tibial fractures using nonreamed flexible intramedullary fixation. AB - Many fixation methods for the treatment of open tibial fractures have been devised, studied, and compared, but controversy persists regarding the most suitable means of immobilization. Nonreamed flexible intramedullary fixation nails, such as Ender rods, have proved an excellent alternative for stabilizing a variety of open tibial fractures with varying degrees of soft-tissue damage. These nails act as an internal splint, which provides three-point fixation; preserves much of the primary blood supply of the tibia; allows for maintenance of length, alignment, and rotation; and facilitates healing of adjacent injured soft tissues. Their use deserves consideration in treating most open diaphyseal tibial fractures. PMID- 2184392 TI - The role of bone grafting in the treatment of delayed unions and nonunions of the tibia. AB - From 1972 to 1984, 53 delayed unions or non-unions of the tibia were successfully treated by either posterolateral or local bone grafting techniques. There were 40 initially open fractures, 19 of which became infected nonunions. The average time from injury to surgery was 10.9 months. Clinical union was achieved in 5.6 months in the posterolateral bone graft group and in 5.4 months in the local bone graft group. There were no refractures or amputations and only one patient continued to drain following bony union. The combination of these surgical techniques allows for an approach to bone grafting of the entire tibia and remains the most effective and reliable form of treatment of the tibial delayed union or nonunion. PMID- 2184393 TI - External fixation for open tibia fractures. A management strategy. AB - The management of open tibia fractures with the Dynamic Axial Fixator, including the method of application and postoperative care, is described. This fixator is utilized until healing. Weight bearing and axial fracture site movement promote an early callus response. The results obtained in the first 35 cases in which it was used at our institution are presented. Thirty-three of the fractures were successfully treated until healing in the external fixator. PMID- 2184394 TI - Body composition, normal electrolyte concentrations, and the maintenance of normal volume, tonicity, and acid-base metabolism. AB - Because the internal environment of the body is largely a fluid medium, the preservation of the volume and composition of the body fluids is absolutely vital to circulatory status and the extraordinarily complicated functions of the human body. The fluid compartments do not exist as fixed spaces with identical compositions but rather are in constant interchange with each other and have strikingly different compositions. Methods of movement of solutes and water include diffusion along electrochemical gradients, by hydrostatic pressure, osmotic forces, bulk flow, primary and secondary active transport, capillary blood flow, and oncotic pressure. Complex feedback control mechanisms exist to ensure homeostasis or equilibrium and include participation by the kidneys, lungs, gastrointestinal tract, the circulatory system, the endocrine system, and the CNS. The maintenance of extracellular volume is centered around the control of balance of the sodium salts. Multiple afferent (or sensing) and efferent (or effector) mechanisms exist to accomplish this homeostasis. The most important determinants of the osmolality or tonicity of the body fluids is the excretion or retention of water by the kidney, thirst mechanisms, and the intake of water. The serum sodium concentration is the laboratory test most often used clinically to assess tonicity. The pH of the body fluids and the major acid-base buffer systems are also carefully regulated. The lungs are responsible for the elimination of the carbon dioxide produced by cellular metabolism, and the kidneys excrete hydrogen ions and regulate the concentration of bicarbonate in the body fluids. Urinary net acid excretion, the hydrogen ions excreted as titratable acid and ammonium ions minus any bicarbonate, equals the acid added to the ECF from the diet and metabolism plus any fecal losses of alkali. PMID- 2184395 TI - Estimation of parenteral fluid requirements. AB - This article reviews the normal physiologic losses of water and electrolytes from the body, the source of the loss, and the increased body loss of water associated with fever. The three different methods for estimating replacement of water and electrolyte losses are described in this review. PMID- 2184396 TI - The management of diarrheal dehydration in infants using parenteral fluids. AB - The assessment and management of an infant with diarrheal dehydration can be reduced to a set of questions. As the questions are studied and answered, the clinician arrives at a rational plan for parenteral fluid therapy, based on physiologic considerations. The selection of the type of fluid to be infused uses a decision-tree algorithm, based on knowledge of the serum sodium consideration. PMID- 2184397 TI - Fluid resuscitation of acute hypovolemic hypoperfusion states in pediatrics. AB - Multiorgan hypoperfusion due to a loss of effective circulating blood volume, whether a consequence of hemorrhage or dehydration, constitutes a medical emergency. Fluid must be added rapidly to the circulatory system, in the form of blood, colloid, or crystalloid solution. The type of fluid used for volume expansion depends on the nature of the losses. The aim of treatment is to expand effective circulating blood volume and to restore nutrient delivery and gas exchange at the cellular level. PMID- 2184398 TI - Oral rehydration therapy. AB - Diarrhea is a major cause of mortality and morbidity affecting infants and children in many parts of the world. Research and understanding of normal and abnormal gastrointestinal physiology allowed the development of oral electrolyte solutions to treat dehydration. These solutions were initially used for treatment of cholera in areas with poor access to medical care and are now used extensively by the WHO. Therapy with OES has expanded to other nonsecretory causes of diarrhea. Two types of solutions are available in the United States. Maintenance solutions contain 40 to 60 mEq per liter of sodium and are used for prevention of dehydration or after rehydration. Rehydration solutions contain 60 to 90 mEq per liter of sodium and are effective for the oral repletion of fluid and electrolyte deficits in both secretory and nonsecretory diarrhea. PMID- 2184399 TI - Special needs of the newborn infant in fluid therapy. AB - The preterm baby, although less able to tolerate high fluid and solute loads, has a remarkable ability to adapt to a rather broad range of environmental challenges, and thus renal function in the preterm infant should no longer be considered impaired. Lower rather than higher fluid administration is the current trend in neonatal care because it is safer and more physiologic. Although changes in body weight over time provide a good indicator of water balance, determination of plasma and urine electrolytes and tonicity are also essential in the monitoring of fluid therapy in preterm infants. PMID- 2184400 TI - Fluid needs in acute renal failure. AB - Derangements of fluid, electrolyte, and acid-base homeostasis are an inevitable part of acute renal failure. Understanding the pathophysiology of these disorders is essential to treating and preventing potentially life-threatening complications. Appropriate nutritional support is also an important part of management in childhood acute renal failure. PMID- 2184401 TI - Hyponatremia. AB - This article provides a useful clinical classification of hyponatremic states based upon plasma tonicity and extracellular fluid volume. The pathophysiology of hyponatremia induced by hypovolemic, euvolemic, and hypervolemic conditions is discussed. An approach to the treatment of each category of hyponatremia is presented. PMID- 2184402 TI - Hypernatremia. AB - Hypernatremia results when the water content of body fluids is deficient compared with sodium content. Hypernatremia can be the result of pure sodium excess but is usually associated with dehydration, secondary to excess losses of water or hypotonic fluids. Hypernatremic dehydration is less common than hyponatremic or isonatremic dehydration, but is associated with the highest morbidity and mortality rate, primarily related to CNS dysfunction. Except when hypernatremia has developed rapidly, the serum sodium concentration should be corrected slowly with frequent monitoring of serum electrolytes. Even then CNS damage can result, either as a consequence of the hypernatremia itself or of rapid lowering of the serum sodium concentration. PMID- 2184403 TI - Ionized calcium: pediatric perspective. AB - Ionized calcium is a physiologically critical calcium pool. It is easily determined, although accuracy depends on sample handling. As a clinical parameter, directly measured ionized calcium has particular import in the care of neonates, patients with sepsis or other cardiovascular instability, massively transfused patients, and those undergoing cardiopulmonary bypass or liver transplantation. Disturbances of calcium occur in many other settings, however, and accurate diagnosis and research conclusions may depend on using the best measurement available. Clinical and investigational use of ionized calcium determinations represent appropriate applications of current proven technology. In the future, clinical calcium manipulation may include modifying specific transmembrane transport processes and intracellular calcium pools and movements. At the current time we are largely restricted to studies of extracellular calcium concentration and its interactions. Much is known, but Mother Nature still has too many secrets. The interested reader is referred to discussions of ionized calcium and hemodynamics, reviews of the endocrine disturbances of calcium and phosphorus, textbook discussions pertinent to general calcium disturbances, and critical care issues. PMID- 2184404 TI - Disorders of potassium homeostasis. AB - Derangements in potassium homeostasis affect the body's bioelectric processes, including muscle contraction, nerve conduction, and myocardial electric pacing. Changes in extracellular potassium concentration occur with altered routes of elimination (renal or gastrointestinal) or with pathologic shifts in potassium from one body fluid compartment to another. The therapeutic interventions may either restore a normal resting potential for excitable cells or affect the threshold potential. Thus, an understanding of the basic pathophysiology is the foundation for treatment. PMID- 2184405 TI - Disorders of acid-base balance. AB - Acid-base disorders are common in sick children. This article is a practical guide to the differential diagnosis and treatment of simple and mixed acid-base disorders of children. Special attention is given to fundamentals of acid-base physiology, to clinical use of the Henderson equation, and to interpretation of readily available laboratory tests. PMID- 2184406 TI - The pharmacology and therapeutics of diuretics in the pediatric patient. AB - Selection of appropriate diuretic therapy in children is hampered by a lack of age-specific pharmacokinetic and pharmacodynamic data, especially in premature neonates. Well-designed clinical trials in neonates, infants, and younger children are necessary prerequisites to safer and more efficacious diuretic therapy. PMID- 2184407 TI - Microbiology of empyema in children and adolescents. AB - The microbiology of empyema was studied in 72 children and adolescents whose specimens yielded bacterial growth after inoculation for aerobic and anaerobic bacteria. A total of 93 organisms, 60 aerobic or facultative and 33 anaerobic, were isolated. Aerobic bacteria was isolated in 48 (67%) patients, anaerobic bacteria in 17 (24%), and mixed aerobic and anaerobic bacteria in 7 (10%). The predominant aerobic or facultative bacteria were Haemophilus influenzae (15 isolates), Streptococcus pneumoniae (13), and Staphylococcus aureus (10). The predominant anaerobes were Bacteroides sp (15 isolates, including 7 Bacteroides fragilis group and 5 Bacteroides melaninogenicus group), anaerobic cocci (9), and Fusobacterium sp (6). beta-lactamase activity was detected in at least one isolate in 20 (37%) of the 54 tested patients. These included all 8 tested S aureus and 7 B fragilis group, 3 of 10 H influenzae, 2 of 4 B melaninogenicus group, and 1 of 2 Klebsiella pneumoniae. Most cases of S pneumoniae and H influenzae were associated with pneumonia. The recovery of anaerobic bacteria was mostly associated with the concomitant diagnosis of aspiration pneumonia, lung abscess, subdiaphragmatic abscess, and abscesses of dental or oropharyngeal origin. The data highlight the importance of anaerobic bacteria in selected cases of empyema in children and adolescents. PMID- 2184408 TI - Increased cerebral blood flow velocity in infants of mothers who abuse cocaine. AB - The pharmacologic effects of cocaine are considered to be secondary to an enhancement of the effects of circulating catecholamines. The effect of intrauterine cocaine exposure on the cerebral blood flow velocity was studied in 20 full-term newborn infants whose urine screens were positive for cocaine and in 18 nonexposed healthy full-term newborn infants whose urine screens were negative for cocaine metabolites. On the first day of life, peak systolic, end diastolic, and mean flow velocities in the pericallosal, internal carotid, and basilar arteries and mean arterial blood pressures were significantly greater in infants who had been exposed to cocaine. On day 2, cerebral blood flow velocities and mean arterial blood pressures were similar in exposed and nonexposed infants. The increase in mean arterial blood pressure and in cerebral blood flow velocity on the first day of life indicates a hemodynamic effect of cocaine that may put the infant exposed to cocaine at a greater risk of intracranial hemorrhage. PMID- 2184409 TI - Role of stereotactic radiosurgery with a linear accelerator in treatment of intracranial arteriovenous malformations and tumors in children. AB - Between 1986 and 1988, 16 children were treated for 10 arteriovenous malformations and 6 recurrent intracranial tumors with stereotactic radiation therapy using a modified Clinac 6/100 linear accelerator. The median age of our patients was 10.5 years. For the group with arteriovenous malformation, follow-up ranged from 6 months to 37 months (median was 20 months). No patient bled during the follow-up period. Five of eight patients with follow-up longer than 12 months have achieved complete obliteration of their arteriovenous malformation by angiogram. The four remaining patients who have not achieved a complete obliteration are awaiting their 2-year posttreatment angiogram. The other patient has been treated within the year and have not yet been studied. Five of the six recurrent tumor patients are alive with a median follow-up of 8 months. The remaining patient was controlled locally, but he died of recurrent disease outside the area treated with radiosurgery. The radiographic responses of these patients have included three complete responses, two substantial reductions in tumor volume (greater than 50%) and one stabilization. Despite previous radiotherapy, there have been no significant complications in these patients. We conclude that stereotactic radiation therapy using a standard linear accelerator is an effective and safe technique in the treatment of selected intracranial arteriovenous malformations and tumors in children. In addition, stereotactic radiosurgery may have unique applications in the treatment of localized primary and recurrent pediatric brain tumors. PMID- 2184410 TI - Medically uninsured children in the United States: a challenge to public policy. AB - This article is an examination of the nature and extent of the problem presented by medically uninsured children in the United States. First, the characteristics of the uninsured population are explored with a description of how age, family income, and employment status disproportionately affect families with children. Second, the Medicaid program and its historically inadequate response to this growing problem of uninsured children is examined. Third, the relationship between insurance status and the health and development of children is discussed. Finally, recent public policy initiatives that have been enacted or proposed to address this inequity in the present health care system are reviewed with a recommendation to establish a "Universal Maternal and Child Health Program." PMID- 2184411 TI - Nephrotic syndrome associated with nonsteroidal anti-inflammatory drug use in two children. AB - Two children with nephrotic syndrome in association with nonsteroidal anti inflammatory drug (NSAID) use are described, and the literature concerning this association is reviewed. NSAIDs are drugs with the potential for causing significant renal toxicity including the nephrotic syndrome, interstitial nephritis, and renal failure even in children without obvious preceding renal disease. Children prescribed such drugs should be regularly monitored with urinalyses and plasma creatinine estimations. The possibility of toxicity to over the-counter use of NSAIDs should be remembered. PMID- 2184412 TI - Vitamin E for prevention of perinatal intracranial hemorrhage. PMID- 2184413 TI - [Treatment of diabetes mellitus in children]. PMID- 2184414 TI - [Cystic papillary carcinoma of the thyroid--sonographic-pathologic correlation]. AB - Ultrasonographic findings of 13 patients with cystic papillary carcinoma (CPC) of the thyroid gland were reviewed retrospectively correlating with pathologic findings. A 4-6 cm oval cystic structure with a 2-3 cm pedunculated projection of mass into the lumen was the characteristic sonographic findings of CPC. However, other sonographic findings of CPC simulated adenoma, nodular goiter or follicular carcinoma. Pathological investigation revealed that malignant cells tended more to be located in intracystic pedunculated mass and/or pericystic region than in the cyst wall. In most of the cases cyst walls were chiefly composed of granulomatous tissue with scattered malignant cells. These findings indicate that the needle biopsy should be done under ultrasonographic guidance to obtain sufficient material for accurate cytologic and/or pathologic diagnosis, thereby reducing the number of false negative cases. PMID- 2184415 TI - [3 cases of ectopic ureteral orifice terminating in the seminal vesicle; efficacy of CT]. AB - We present three cases of ectopic ureteral orifice terminating in the seminal vesicle. The enlarged seminal vesicle, ipsilateral renal agenesis or hypoplasia and the absence of normal ureteral orifice are the triad of CT findings in this disease. PMID- 2184416 TI - [Two cases of solid and cystic tumor of the pancreas (including one case of MRI)]. AB - Solid and cystic tumor of pancreas is an uncommon neoplasm which is histologically low grade malignant but amenable to cure by surgical excision. It tends to occur in young women. US and CT depict a well circumscribed mass that can be solid, mixed solid and cystic and largely cystic. Their ratio depends on the degree of hemorrhage and necrosis. Angiography shows a mildly to moderately vascular mass which corresponds to solid parts. MRI is useful to detect the hemorrhage which is common in this tumor. PMID- 2184417 TI - Making sense of ... wound closure. PMID- 2184418 TI - Nurse education. How to organise 'brainstorming'. PMID- 2184419 TI - Characterization of castration-induced cell death in the rat prostate by immunohistochemical localization of cathepsin D. AB - Activities of cathepsin D (EC 3.4.23.5) were determined in three lobes of the prostate during their involution by both biochemical and immunohistochemical procedures. The activity of cathepsin D in noncastrated rats was 0.9 +/- 0.2 (mean +/- SE) 5.7 +/- 0.6, and 13.1 +/- 0.8 units/mg protein for the ventral, lateral, dorsal lobes, respectively. Following castration, there was a significant increase in enzymatic activity in all three lobes within 2-3 days. In the ventral lobe, the activity peaked in 5 days to 6.2 +/- 0.9 units/mg protein and declined slightly thereafter. In the lateral and dorsal lobes, the activity remained elevated (14-20 units/mg protein) throughout the postcastration period studied. Immunohistochemical staining of cathepsin D was localized in the cytoplasm of prostatic epithelial cells as fine discrete lysosomal granules. These granules were larger and more abundant in the dorsal and lateral lobes than in the ventral lobe and were not detected in prostatic stromal cells and seldom in the luminal fluid. Castration resulted in an immediate increase in the size and number of these granules in the epithelial cells, followed by a sudden further increase in cathepsin D staining in some but not all epithelial cells. Lysosomal granules gradually coalesced in these cells to form large vacuoles that fit the characteristic description of apoptotic bodies. Finally, after day 7 postcastration, collapse and disintegration of the entire glandular structure was noted. Using this procedure to localize cathepsin D as a tool, we were able to follow the morphological events of prostatic cell death during castration-induced involution in the rat at the light microscopic level. PMID- 2184420 TI - The pharmacokinetics of tricyclic antidepressant drugs in the elderly. AB - Antidepressants, especially tricyclic agents (TCAs), are increasingly used in geriatric patients since depression is a common mood disorder in the elderly and the size of elderly population is increasing. Notwithstanding the importance of kinetics to better use of drugs, its study in the elderly (regarding TCAs) is not sufficiently developed. The present paper briefly reviews the available data on amitriptyline, nortriptyline, protriptyline, imipramine, desipramine and clomipramine kinetics in the elderly. PMID- 2184421 TI - Endotoxin inhibition of drinking behaviour in the rat. AB - Intravenous (i.v. 320 and 640 micrograms/kg) and intracerebroventricular (i.c.v.; 1 microgram/rat) injection of Escherichia coli lipopolysaccharide (LPS) powerfully inhibited drinking induced by 24 h water deprivation. Pretreatment with acetylsalicylic acid (ASA) into the preoptic area (POA) completely abolished the effect induced by i.v. LPS, but did not modify that elicited by i.c.v. LPS. Intraperitoneal ASA injections significantly reduced the antidipsogenic effect of i.c.v. LPS. Electrolytic ablation of the subfornical organ (SFO) did not modify the effect induced by either i.v. or i.c.v. LPS. Present findings indicate that: (1) the antidipsogenic effect of i.v. LPS is mediated by prostaglandin synthesis into the POA, (2) the SFO is not involved in this effect, and (3) prostaglandins in other brain areas, besides POA, modulate the effect of i.c.v. LPS. It is suggested that at least two different brain sites, inside the blood-brain barrier, might be involved in the antidipsogenic effect of LPS. PMID- 2184422 TI - Evidence of the involvement of D1 dopamine receptors in PCP-induced stereotypy and ataxia in rabbits. AB - A behavioural study on the effects of D1 and D2 dopamine receptor antagonists (SCH 23390 and sulpiride respectively) and of an A1 adenosine receptor agonist (N6-L-phenylisopropyladenosine, L-PIA) against phencyclidine (PCP)-induced effects was assessed in adult male rabbits. SCH 23390 (0.003-0.01 mg/kg i.v.) and sulpiride (12.5 mg/kg i.v.) were able to significantly prevent PCP-induced stereotypy. Ataxia was reduced by SCH 23390 (0.003 mg/kg i.v.), while it was potentiated by sulpiride (12.5 mg/kg i.v.). Given alone at 12.5 mg/kg, sulpiride induced some EEG and behavioural effects in rabbits, while SCH 23390 (0.003 and 0.01 mg/kg) did not. L-PIA prevented both PCP-induced stereotypy and ataxia at the dose (0.1 mg/kg i.v.) devoid of behavioural or EEG effects by itself. Our results suggest that D1 dopamine receptors might play a more important role than D2 receptors in the expression of PCP-induced behaviour. They also propose that A1 adenosine receptors might be involved (e.g. via an influence on the dopamine release) in the behavioural effects of PCP. PMID- 2184423 TI - Insulinic actions of vanadate in diabetic rats. AB - Oral administration of sodium orthovanadate (0.3 mg/dl) normalizes blood glucose and reduces glycosylated HbA1 levels in streptozotocin induced diabetic rats without any increase in the serum insulin levels. However, diabetic condition reappears after withdrawal of vanadate. Assays of carbohydrate metabolizing enzymes clearly indicate that vanadate activates the glycolysis, glycogenesis and depresses the glycogenolysis and gluconeogenesis in diabetic rats. These results demonstrate that vanadate substitutes insulin action in chronic experimental diabetics. PMID- 2184424 TI - Transgenic animals as bioreactors for pharmacological products. PMID- 2184425 TI - Metronidazole and antipyrine as probes for the study of foreign compound metabolism. AB - The aim of the present work was to develop a tool for the study of the enzyme activities relevant for the biotransformation of foreign compounds, their elimination and/or activation to toxic substances. The activity of an enzyme may be assessed by the rate of metabolism of a preferably specific probe or model compound. The cytochrome P450'ies, the key enzymes for the elimination and/or activation of most foreign compounds, exist in multiple forms with variable substrate specificity and regulation. Some cytochrome P450'ies are under genetic control, whereas the activity of others is mainly regulated by the influence from factors in the environment. Only some of the cytochrome P450'ies are relevant for the formation of harmful metabolites. Thus, the activity of as many cytochrome P450 forms as possible should be assessable, preferably simultaneously. The present work evaluated metronidazole in a cocktail with antipyrine as a tool for the study of the regulation of foreign compound metabolism in the liver. The cytochrome P450 catalyzed metabolism of metronidazole and antipyrine was studied in humans and in isolated rat hepatocytes. In humans the influence of dose, route of administration, enzyme induction and inhibition and liver disease was investigated. Rats of either sex were studied with and without pretreatment with specific enzyme inducers and incubations included specific enzyme inhibitors. Evidence was provided that the oxidative formation of the five major metabolites, two from metronidazole and three from antipyrine, depends on different cytochrome P450'ies. In humans it was demonstrated that the clearance of metronidazole and antipyrine could be determined from the same saliva sample collected 16-24 hours after their oral administration and so could the clearance for formation of each metabolite if urine was collected for 48 hours. Thus, with the cocktail of metronidazole and antipyrine and simple non-invasive sampling the activity of five different cytochrome P450'ies can be assessed in vivo. In addition, metronidazole may also be used for assessment of the glucuronidation capacity although this is a minor pathway in man. Because the variation within subjects is much less than between them, the cocktail test is particularly suited for paired designs with measurements before and after an environmental change and the subjects serving as their own control. The metronidazole/antipyrine cocktail may have many applications in the study of the regulation of foreign compound metabolism in man and in animals, in vivo and in vitro. PMID- 2184426 TI - [Campylobacter pylori-Helicobacter pylori. A long development]. PMID- 2184427 TI - [Systemic amyloidoses. Immunohistochemical typing at the time of autopsy using a series of specific antibodies]. PMID- 2184428 TI - [Immunohistochemical detection of progesterone receptors in breast cancer. Comparison of antibodies mPRI and PR-ICA]. PMID- 2184429 TI - [The reaction of the gastrointestinal tract to insulin-induced hypoglycemia in patients with type-1 diabetes mellitus complicated by diabetic enteropathy]. PMID- 2184430 TI - [An automated work place for the diabetologist (the problems of monitoring diabetic patients)]. PMID- 2184431 TI - [A comparison of the hormonal and etholotropic activity of luliberin and its analogs]. AB - The paper is devoted to comparative analysis of the activity of peptides (LH-RH analogs) with relation to their action on ovulation as well as on the learning capabilities and their effect on immobilization stress in rats. The acceleration of learning processes and elimination of immobilization stress were shown to be caused by LH-RH and its analogs, regulating actively ovulation under experimental conditions. The comparative evaluation of their action has shown that LH-RH analogs-antagonists produce a more marked effect on the process of learning and elimination of stress consequences than its analogs-agonists. PMID- 2184432 TI - Thermitase and proteinase K: a comparison of the refined three-dimensional structures of the native enzymes. AB - We compare the three-dimensional structures of thermitase and of proteinase K determined by X-ray crystallography to a resolution of 1.4 and 1.48 A respectively. Both enzymes are relatively stable towards heat and denaturating agents and are representative of a subgroup of subtilisins characterized by a free SH group close to the active site histidine. Even though they have low sequence homology, the overall tertiary structures are highly conserved. The high resolution structures are compared in terms of the overall fold of the molecules, the active sites, the calcium binding sites, disulphide bridge positions, the positions of the charged residues and the solvent structure. Most subtilisins such as thermitase are of prokaryotic origin and proteinase K is up to now the only known eukaryotic structure. PMID- 2184433 TI - Crystallization and structure solution at 4 A resolution of the recombinant synthase domain of N-(5'-phosphoribosyl)anthranilate isomerase:indole-3-glycerol phosphate synthase from Escherichia coli complexed to a substrate analogue. AB - The recombinant synthase domain of the bifunctional enzyme N-(5' phosphoribosyl)anthranilate isomerase:indole-3-glycerol-phosphate synthase from Escherichia coli has been crystallized, and the structure has been solved at 4 A resolution. Two closely related crystal forms grown from ammonium sulphate diffract to 2 A resolution. One form (space group R32, a = 163 A, alpha = 29.5 degrees) contains the unliganded synthase domain; the second crystal form (space group P6(3)22, a = 144 A, c = 158 A) is co-crystallized with the substrate analogue N-(5'-phosphoribit-1-yl)anthranilate. The structure of the synthase inhibitor complex has been solved by the molecular replacement method. This achievement represents the first successful use of a (beta alpha)8-barrel monomer as a trial model. The recombinant synthase domain associates as a trimer in the crystal, the molecules being related by a pseudo-crystallographic triad. The interface contacts between the three domains are mediated by those residues that are also involved in the domain interface of the bifunctional enzyme. This system provides a model for an interface which is used in both intermolecular and intramolecular domain contacts. PMID- 2184434 TI - Introduction of internal cysteines as conformational probes in yeast phosphoglycerate kinase. AB - Several mutants of yeast phosphoglycerate kinase, each containing only one internal cysteine residue, were constructed from a single mutant devoid of cysteine. These cysteines were introduced as local conformational probes in selected buried positions. The enzyme activity, conformational characteristics and stability indicated that the mutations introduced only small perturbations in the molecule. The folding-unfolding process mediated by guanidine hydrochloride under equilibrium conditions was studied by following the variations in ellipticity and the reactivity of the cysteine residue towards 5,5' dithiobis(nitrobenzoate). The process was found to be reversible except for mutant C97A, V49C, suggesting that this region located in helix I might be crucial in determining an intermediate on the folding pathway. The transitions obtained by the two signals did not coincide, indicating that the local structures, in several parts inside the molecule, are more sensitive to the denaturant than the overall conformation. PMID- 2184435 TI - Metallothioneins with interdomain hinges expanded by insertion mutagenesis. AB - Specific peptides of varying lengths were inserted between the two metal cluster domains of metallothionein (MT), which normally are spanned by only three amino acids, Lys-Lys-Ser. These interdomain expansions were made to test if such structural alterations would affect MT function. These constructs were engineered by inserting defined oligonucleotides of up to four tandem repeats of dodecanucleotides and hexanucleotides into an Alu-1 endonuclease cleavage site, which separates the two exonic regions of an MT-coding sequence from Chinese hamster ovary cells, MT-2. The native and altered sequences were cloned into a high expression Escherichia coli-yeast shuttle vector and used to transform yeast cells whose endogenous MT genes had been previously deleted. Using metal resistance as a biological marker, all constructs were shown to be functional in rendering the host cells resistant to either copper or cadmium. As the inserts, by nature of their amino acid sequence, could add flexibility to the otherwise compact molecule, the two domains apparently are active independently. The level of activity, however, diminished with the length of the insert. Determinations for copy number of the chimeric plasmids and MT mRNAs in the transformed cells showed that the replicational and transcriptional capacity of the long and short constructs were equivalent. PMID- 2184436 TI - Alpha-helical coiled coils and bundles: how to design an alpha-helical protein. PMID- 2184437 TI - An expectation maximization (EM) algorithm for the identification and characterization of common sites in unaligned biopolymer sequences. AB - Statistical methodology for the identification and characterization of protein binding sites in a set of unaligned DNA fragments is presented. Each sequence must contain at least one common site. No alignment of the sites is required. Instead, the uncertainty in the location of the sites is handled by employing the missing information principle to develop an "expectation maximization" (EM) algorithm. This approach allows for the simultaneous identification of the sites and characterization of the binding motifs. The reliability of the algorithm increases with the number of fragments, but the computations increase only linearly. The method is illustrated with an example, using known cyclic adenosine monophosphate receptor protein (CRP) binding sites. The final motif is utilized in a search for undiscovered CRP binding sites. PMID- 2184438 TI - A novel parathyroid hormone-related protein: role in pathology and physiology. AB - Many factors, such as interleukin 1, TGF alpha, TNF alpha, and beta and prostaglandins, have been implicated in aetiological roles in HHM (Martin and Mundy, 1987). Much interest in the past has also centered upon the likelihood of ectopic secretion of PTH in this condition. We have purified a protein (PTHrP) implicated in HHM from a human lung cancer cell line (BEN). Full-length cDNA clones have been isolated and found to encode a prepropeptide of 36 amino acids and a mature protein of 141 amino acids. Eight of the first 13 amino acids were identical with human PTH, although antisera directed to the NH2-terminus of PTHrP do not recognize PTH; this homology is not maintained in the remainder of the molecule. PTHrP therefore represents a previously unrecognized hormone, possibly related to the PTH gene by a gene duplication mechanism. In support for this notion, the PTHrP gene has been localized to the short arm of chromosome 12; it is believed that chromosome 11, containing the PTH gene, and chromosome 12 are evolutionarily related. In addition, the human PTHrP gene has been isolated, characterized, and shown to have a similar intron/exon organization as the PTH gene. It is possible that the original ancestral gene is indeed the PTHrP gene; resolution of this question awaits studies in lower species. Peptides synthesized to the predicted protein sequence have enabled detailed structure-function studies that have identified NH2-terminal sequences to be responsible for the biological effects of the molecule. Antibodies raised against the various synthetic peptides have led to the immunohistochemical localization of PTHrP in many human squamous cell carcinomas as well as in subpopulation of keratinocytes of normal skin. The availability of these antibodies has opened the way for the development of a radioimmunoassay to detect PTHrP in the sera of cancer patients at risk of developing hypercalcemia. The recent characterization of PTHrP-like activity in the ovine fetus suggests some physiological function for PTHrP. It is possible that PTHrP, as the fetal counterpart of PTH, has the role of maintaining the maternal-fetal calcium gradient. The isolation and characterization of PTHrP has added to our understanding of the mechanisms of hypercalcemia, and may contribute to the understanding of other metabolic bone diseases such as osteoporosis and Paget's disease. Finally, and perhaps most importantly, PTHrP may play a hitherto unrecognized role in fetal calcium metabolism and in normal cell physiology. PMID- 2184439 TI - The role of prostaglandins in the local regulation of bone metabolism. PMID- 2184440 TI - Treatment of vertebral osteoporosis with fluoride and calcium. PMID- 2184441 TI - The putative role of secretory protein-I/chromogranin A as a precursor for regulatory hormones. PMID- 2184442 TI - Production of 1 alpha,25-dihydroxyvitamin D3 by hematopoietic cells. AB - Perhaps, 1 alpha,25(OH)2D3 plays a role as a co-factor in the communication between lymphocytes and macrophages. A schematic representation of that proposed interaction is shown in Figure 2. (Formula: see text). For example, macrophages encounter bacteria, stimulating these cells to begin chemotaxis, phagocytosis, and killing of the microorganisms. In addition, the cells produce interleukin-1. Both interleukin-1 and bacterial antigens in the context of the Ia antigens of the macrophages activate T lymphocytes. The T lymphocytes begin to synthesize lymphokines which can further activate macrophages. Macrophages stimulated by IFN gamma eventually synthesize 1 alpha,25(OH)2D3. Activated lymphocyte express receptors for 1 alpha,25(OH)2D3; and their lymphokine production will decrease in the presence of 1 alpha,25(OH)2D3. PMID- 2184443 TI - Recent studies on the biological actions of vitamin D on intestinal transport and the electrophysiology of peripheral nerve and cardiac muscle. AB - Vitamin D, with parathyroid hormone and calcitonin, is an essential factor in the homeostatic regulation of systemic calcium in most vertebrate species. Targets for this aspect of vitamin D action, through its biologically active metabolites, are primarily the intestine, kidney and bone. Each of these tissues or organs are stimulated by 1,25(OH)2D3 to increase the transport calcium into the extracellular fluid compartment when plasma calcium levels are below normal and/or when there is a greater need for calcium to meet the requirements of physiological processes, such as growth, gestation and lactation. During such periods, the efficiency of the absorption of calcium from the intestine increases, the resorption of calcium salts from bone is stimulated, and the efficiency of the reabsorption of filtered calcium by the renal tubule is increased. In addition to the homeostatic function of vitamin D, there is an increasing amount of evidence that vitamin D has important effects on tissues and organs other than those concerned with calcium homeostasis. With regard to the intestinal epithelial system, the genomic effect of 1,25(OH)2D3 was shown several years ago when the de novo synthesis of a specific vitamin D-induced calcium binding protein (CaBP, calbindin-D) was demonstrated. In our view, this appears to be an essential factor in the well-documented enhancement of calcium absorption by vitamin D. The function of calbindin-D, a high affinity calcium binding protein, in the absorptive process is not precisely known but currently considered to act as an intracellular facilitator of the diffusion of calcium from the microvillar pole of the enterocyte to the basal-lateral membrane. There is evidence that vitamin D influences another step in the absorptive process. This step appears to be associated with the entrance of luminal calcium into the enterocyte, the first step in the transepithelial transport process. This response appears to occur relatively early (1 h or less) after 1,25(OH)2D3 is given to vitamin D-deficient animals, whereas the de novo synthesis of transport proteins has a much longer lag time (about 4 h). The in vitro absorption studies of Nemere et al (1984) and the in vivo experiments of our group (Wasserman et al, 1982) accentuate this point. However, the more rapid reaction, i.e., the possible modification of the permeability properties of the brush border membrane, does not result in a substantive increase in overall calcium absorption unless the enterocyte had been "primed" by previous exposure to vitamin D. The "priming" reaction might represent the synthesis of CaBP or some other intracellular component.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2184444 TI - [Transnasal administration of drugs. 2. Models for studying nasal absorption in animals and parameters susceptible to influence]. PMID- 2184445 TI - Drug transport in the central nervous system: role of carriers. AB - The rate of entry into and distribution of many drugs in the mammalian brain cannot be explained by the physicochemical characteristics of these drugs taking into account the anatomy of the blood-brain barrier. Rather, specialized mechanisms (carriers) in the central nervous system have been sought after and characterized. These carriers explain the observed pharmacokinetic behavior of many drugs in brain. This review summarizes these data in the context of the blood-brain barrier and focuses on several broad principles and selected examples. PMID- 2184446 TI - [Karl Bonhoeffer and the concept of symptomatic psychoses]. AB - Against the background of the lifetime of Karl Bonhoeffer, March 31, 1868 to December 4, 1948, and the eighty-year-old concept of symptomatic psychoses, a sketch of the latter is set out and its present significance in symptomatology and research followed up. PMID- 2184447 TI - [Does symptomatic schizophrenia exist?]. AB - The question if there are "symptomatic schizophrenias" has been discussed since the 20s. Schizophrenic psychoses caused be definable and well known brain diseases are presented. All schizophrenic symptoms and syndromes, the first rank symptoms (K. Schneider) too, occur in somatically founded psychoses. The group of paroxysmal transition syndromes in the sense of aura prolongata (continua) and the episodic schizophrenic psychoses in psychomotor epilepsy may be a model for the schizophrenia research. Vital threatening, so-called pernicious catatonic schizophrenias are found on the basis of infectious brain diseases, sometimes only diagnosed in autopsy. Beside acute and reversible symptomatic schizophrenic psychoses there are, even if rarely, recurrent and chronic courses of symptomatic schizophrenias. That certain conditions for the developing of symptomatic schizophrenias are rarely realised, could be an explanation for their rarity. Some findings indicate that the limbic system is significant for symptomatic (and idiopathic) schizophrenic psychoses and the pre- and postpsychotic basic stages determined by dynamic and cognitive basic symptoms, which are phenomenologically very similar to aura symptoms released by stereoelectroencephalographic depth recordings (Wieser). The characteristic features of marked fluctuation, discontinuity and insteadiness of the cognitive thought, perception, psychomotor and cenesthetic phenomena do not speak against an organic brain disorder provided that the traditional process hypothesis is abandoned in favor of a neurobiochemic disorder, fluctuating on its part depending on endogenous as well as psychic reactive factors. PMID- 2184448 TI - [Endogenous and symptomatic schizophrenia. Wherein lies the difference?]. AB - It is the opinion of the present writer that endogenous and symptomatic schizophrenia are two completely different matters. By classical symptomatology it is impossible to establish the distinction in every individual case. Nevertheless, in not one of the published cases known to us did Bonhoeffer err in his diagnosis of the one or the other. Evidently he made use of additional characteristica gathered in practice, about which he himself may not always have been quite clear. PMID- 2184449 TI - [The symptomatic psychosis of Friedrich Nietzsche, made evident by his last attempt at an autobiography]. AB - Nietzsche's autobiography gestates neither conflicts, nor life problems, nor matter suppressed from his subconscious, nor are the speech distortions of the schizophrenic patient to be found. In all, analysis allows with certainty the conclusion that is was written by a sick person suffering from a psycho-organic disorder of the kind Bonhoeffer referred to by the general term "symptomatic psychosis". PMID- 2184450 TI - [The Korsakoff concept of Karl Bonhoeffer and its relation to the psychometrics of amnestic disorders]. AB - Karl Bonhoeffer set great value on the precise description of psychopathological findings, and was the first to stress the very close relationship between Wernicke's encephalopathy and Korsakoff's psychosis. Proof of mnestic deficiency is still today very important in the exact analysis of chronic symptomatic psychoses. Knowledge acquired in neuropsychology must be incorporated into psychopathometry to enable a more exact analysis of chronic cerebral psychosyndromes. The paper presents a new test to measure mnestic deficiency, suitable for the examination of patients with pseudoneurasthenic syndromes, organic change of personality, or mild early forms of dementia. PMID- 2184451 TI - Darwin's illness: a biopsychosocial perspective. AB - Throughout an illustrious scientific career, Charles Robert Darwin (1809-1882) suffered from a mysterious and disabling malady. The illness, which was characterized by depressed feelings and violent and uncomfortable cardiac palpitations, gastric upsets, and headaches, began shortly after Darwin returned from a five-year voyage to South America as the naturalist of the Beagle. One explanation for Darwin's symptoms is he suffered from Chagas' disease as a result of being bitten by an insect common to South America. More psychodynamically oriented theorists speculate that Darwin's illness was an expression of repressed anger toward his father. Others have noted a familial vulnerability to the symptoms Darwin described. The author examines these theories and suggests that they all may have validity in explaining the mysterious illness of Charles Darwin. PMID- 2184452 TI - Neurasthenia in the 1980s: chronic mononucleosis, chronic fatigue syndrome, and anxiety and depressive disorders. AB - In the 1980s, patients suffering from unexplained fatigue and what seemed like a prolonged attack of acute mononucleosis were given the diagnosis of chronic mononucleosis or chronic infection with the Epstein-Barr virus. Although the diagnosis has great appeal, the Epstein-Barr virus does not cause the syndrome (CFS) of chronic fatigue, which has been renamed and redefined chronic fatigue syndrome to remove the inference that the virus is its cause. From a historical perspective, both syndromes represent the 1980s equivalent of neurasthenia, a disease of fatigue that influenced the development of psychiatric nosology. Because patients with depression and anxiety also have chronic fatigue and because most patients with CFS have an affective disorder, the assessment of organic causes of this syndrome requires careful psychiatric diagnosis and treatment. Defining chronic fatigue syndrome as a medical disorder may deprive patients of competent treatment of their affective disorder. PMID- 2184453 TI - Myocardial infarction and patients' wives. AB - When a patient has a myocardial infarction (MI), all aspects of marital function are affected. Soon after the MI, patients' wives experience psychological distress that decreases with time. Illness behaviors among the MI patients' wives increase, and aggressive and sexual impulses are often inhibited. Many families experience changes in members' work status after the husband has an MI, and wives are faced with increased chores. Marital interaction also changes. Dysfunctional marital relationships are associated with a poor psychosocial outcome. Additionally, spousal factors such as dependency are also likely to affect patients. Intervention strategies are best directed to wives at risk for problems. PMID- 2184454 TI - The concept of abnormal illness behavior. PMID- 2184455 TI - [Fractures in the region of the elbow joint]. AB - The knowledge of the normal anatomy and ossification centers of the elbow joint as well as the knowledge about bone density distribution, age distribution and fracture mechanisms are tools for the diagnostic work-up of injuries about the elbow. This paper gives basic informations for the understanding of typical elbow fractures and discusses diagnostic difficulties. PMID- 2184456 TI - [Hemophilic osteoarthropathy with special reference to the elbow joint]. AB - Hemophilia is a rare disorder, whereby recurrent bleedings into the joint can result in osteoarthropathy. Radiological changes consist of osteoporosis, enlargement of the epiphyses, irregularity of the subchondral bone surface, narrowing of the joint space, cysts, erosions, joint incongruence and joint deformity. The earlier and the more frequent bleedings have occurred that have not been treated adequately, the more of the changes mentioned above are present. In children, osteoarthropathy of the elbow is present in only about 50% of cases, and in the remaining cases the degree is mostly minimal or moderate. Differential diagnosis consists of juvenile rheumatoid arthritis in children, and rheumatoid arthritis and osteoarthritis in adults. PMID- 2184457 TI - [The basis for ultrasonic phenomena during the injection of x-ray contrast media]. AB - During the injection of contrast media for cerebral angiography, high-intensity ultrasound reflections can be recorded by Doppler sonography and B-mode scanning. This phenomenon was examined during carotid angiography and by in vitro experiments in tube models. Our results show that these high-intensity reflections are caused by: (1) transient interfaces of impedance between small compartments of contrast medium and blood and (2) small gas bubbles, which are always present in freshly aspirated contrast medium. Therefore, intraarterially injected contrast medium acts as an ultrasound contrast medium as well. PMID- 2184458 TI - [Sonography in breast diagnosis]. AB - In a prospective study of 235 tissue masses verified histologically, we examined the diagnostic contribution of ultrasound in comparison to mammography. When the two methods were combined, 96.8% of all malignant neoplasms could be diagnosed correctly. Most (90.5%) were found by mammography alone and 4.8% were detectable by ultrasonography but not by mammography. Despite relatively good results in the evaluation of solid masses, it is not advisable to omit tissue examination. The superiority of ultrasound over mammography in the diagnosis of cystic lesions could lead to a significant reduction in needle aspirations and biopsies. PMID- 2184459 TI - [Biomechanics of the hip joint]. AB - The load of the hip joint is related to the density of bone, thickness of cartilage and pattern of the cancellous bone. The X-rays of the hip joint must provide all information for the calculation of the individual strain and stress. PMID- 2184460 TI - [Prevention of adverse reactions to contrast media by means of general anesthesia?]. AB - Adverse reactions to systemically administered contrast media are a threat to patients as well as the responsible physician. Non-ionic media produce less side effects due to the lower osmolarity and an advantageous chemical structure. Suggested prophylactic measures include the intravenous administration of H1- and H2-receptor blockers the administration of corticosteroids, sedatives and general anaesthesia. General anaesthesia not necessarily protects from a reaction to either ionic or nonionic compounds and bears its own risks. PMID- 2184461 TI - [Structure and function of tryptophan synthase]. PMID- 2184462 TI - [Physiological roles of mtDNA of higher animals]. PMID- 2184463 TI - [Structure and function of fatty acid binding proteins]. PMID- 2184464 TI - Health risk assessment of environmental exposure to trichloroethylene. AB - A review of the animal data showed trichloroethylene (TRI) to be of low acute toxicity. Repeated exposure showed that the target organs were the liver, and to a lesser extent, the kidney. TRI is not mutagenic or only marginally mutagenic. There is no evidence of fetotoxicity or teratogenicity. TRI is judged not to exhibit chronic neurotoxicity. Lifetime bioassays resulted in tumors in both the mouse and the rat. However, because of qualitative and quantitative metabolic differences between rodent and human, no one suitable tumor site can be chosen for human health risk assessment. In addition, of the several epidemiology studies, none has demonstrated a positive association for increased tumor incidence. A review of the health effects in humans shows TRI to be of low acute toxicity and, following chronic high doses, to be hepatotoxic. Environmental exposure to TRI is mainly via the atmosphere, while the contribution from exposure to drinking water and foodstuffs is negligible. The total body burden was calculated as 22 micrograms/day. The safety margin approach based on human health effects showed that TRI levels are well within the safety margin for the human no-observable-effect level (10,000 times lower). The total body burden represents a risk of 1.4 X 10(-5) by linearized multistage modeling. Therefore, by either methodological approach to risk assessment, the environmental occurrence of TRI does not represent a significant health risk to the general population or to the population in areas close to industrial activities. PMID- 2184465 TI - Chlorine dioxide and hemodialysis. AB - In the United States chlorination of potable water supplies has been the standard method of disinfection for about 75 years. In recent times concern has been raised about the propensity of chlorination to introduce potentially carcinogenic trihalomethanes (THM) such as chloroform into finished water. The levels of THM introduced depend on many factors including the quality of the raw water. Numerous community water treatment facilities are experiencing difficulty in meeting current U.S. Environmental Protection Agency standards, and it is likely that the permissible levels may be lowered in the future. An alternative to chlorination which does not generate THM during disinfection is chlorine dioxide, but there are concerns about the acute and chronic toxicity of ClO2 and its disinfection by-products, chlorite and chlorate. Deleterious effects of moderately high levels of these oxychlorines have been demonstrated experimentally on red blood cells, thyroid function, and development in laboratory animals. Adverse effects in controlled prospective studies in humans and in actual use situations in community water supplies have as yet failed to reveal clear evidence of adverse health effects. Among groups who may be at special risk from this suggested alternative are patients who must undergo chronic extracorporeal hemodialysis. The special needs, precautions, and experience to date in regard to finished water are reviewed. Again, very limited human experience has failed to reveal adverse health effects. Further study, caution, and extreme vigilance are indicated, but dialysis patients in carefully controlled facilities may be at no greater risk than the general population. PMID- 2184466 TI - Human risk assessment of carcinogens from an administrative perspective. AB - For evaluation of the carcinogenic potency of an environmental chemical or a mixture of chemicals, epidemiological or workplace studies, animal studies, and in vitro tests are the three major strategies used. Asbestos fibers and 1,2 dichloroethane are chosen as examples. They illustrate that the strategies may enable the implementation of measures by health authorities. PMID- 2184467 TI - Relevance of maximum tolerated dose to human carcinogenic risk. PMID- 2184468 TI - Nonclinical toxicity studies of antiviral drugs indicated for the treatment of non-life-threatening diseases: evaluation of drug toxicity prior to phase 1 clinical studies. AB - The types of nonclinical toxicity studies conducted during the preclinical research and development of antiviral drugs intended for the treatment of non life-threatening diseases in humans are reviewed. This guidance also applies to other classes of drugs under development for non-life-threatening diseases that fall under the regulatory responsibility of the Food and Drug Administration's Division of Antiviral Drug Products, including systemic antifungals, antimycobacterials, and immunomodulators. PMID- 2184469 TI - Health risk assessment of environmental exposure to 1,1,1-trichloroethane. AB - In 1986 a survey was published by CEFIC on the occurrence of chlorinated solvents in ambient air, in surface water, and in ground water. The present article concentrates on 1,1,1-trichloroethane (1,1,1-T), and puts into perspective the environmental occurrence and the toxicity. Critical toxicological data are briefly discussed. As no evidence of a carcinogenic effect of 1,1,1-T is apparent, the no-adverse-effect levels in chronic inhalation exposure in rats (875 ppm) and mice (1500 ppm) form the basis for the estimation of potential risk to human health. Environmental exposure to 1,1,1-T is mainly via the atmosphere (120 micrograms/day); the contributions of drinking water (2 micrograms/day) and food (3 micrograms/kg) are negligible. Safety margins are calculated by comparing the no-adverse-effect levels in rat and mouse studies with the total body burden. Safety margins are also calculated after converting no-adverse-effect levels into estimated internal dose levels by physiologically based pharmacokinetic modeling. Safety margins vary with the starting point, but are of the order of 10(5) for the general population and more than 10(4) for the population close to industrial activities. It may be concluded that the risk of a potential health effect resulting from environmental exposure to 1,1,1-trichloroethane is negligible. PMID- 2184470 TI - Mortality risks induced by economic expenditures. AB - Existing evidence shows that lower incomes are associated with higher mortality risks. This paper examines the implications for fatalities when the relationship is interpreted as an induced relationship, meaning that lower incomes will on average lead to higher mortality risks. A model is developed for estimating the number of fatalities possibly induced by economic expenditures. This model accounts for different allocations of the expenditures on family units with varying income levels. Illustrative calculations provide insights about the possible significance of fatalities induced by economic expenditures. These results suggest that some expensive regulations and programs intended to save lives may actually lead to increased fatalities. Important caveats to reduce the likelihood of misinterpreting or misusing the results are included. PMID- 2184471 TI - Knowledge-based representations of risk beliefs. AB - Beliefs about risks associated with two risk agents, AIDS and toxic waste, are modeled using knowledge-based methods and elicited from subjects via interactive computer technology. A concept net is developed to organize subject responses concerning the consequences of the risk agents. It is found that death and adverse personal emotional and sociological consequences are most associated with AIDS. Toxic waste is most associated with environmental problems. These consequence profiles are quite dissimilar, although past work in risk perception would have judged the risk agents as being quite similar. Subjects frequently used causal semantics to represent their beliefs and "% of time" instead of "probability" to represent likelihoods. The news media is the most prevalent source of risk information although experiences of acquaintances appear more credible. The results suggest that "broadly based risk" communication may be ineffective because people differ in their conceptual representation of risk beliefs. In general, the knowledge-based approach to risk perception representation has great potential to increase our understanding of important risk topics. PMID- 2184472 TI - Assessing exposures to environmental tobacco smoke. AB - The combustion of tobacco indoors results in the emission of a wide range of air contaminants that are associated with a variety of acute and chronic health and comfort effects. Exposures to environmental tobacco smoke (ETS) are assessed for epidemiologic studies and risk assessment and risk management applications. An individual's or population's exposure to ETS can be assessed by direct methods, which employ personal air monitoring and biomarkers, and indirect methods, which utilize various degrees of microenvironmental measurements of spaces, models, and questionnaires in combination with time-activity information. The major issues related to assessing exposures to ETS are summarized and discussed, including the physical-chemical nature of ETS air contaminants, use of proxy air contaminants to represent ETS, use of biomarkers, models for estimating ETS concentrations indoors, and the application of questionnaires. PMID- 2184473 TI - Risk assessment methodologies for passive smoking-induced lung cancer. AB - Risk assessment methodologies have been successfully applied to control societal risk from outdoor air pollutants. They are now being applied to indoor air pollutants such as environmental tobacco smoke (ETS) and radon. Nonsmokers' exposures to ETS have been assessed based on dosimetry of nicotine, its metabolite, continine, and on exposure to the particulate phase of ETS. Lung cancer responses have been based on both the epidemiology of active and of passive smoking. Nine risk assessments of nonsmokers' lung cancer risk from exposure to ETS have been performed. Some have estimated risks for lifelong nonsmokers only; others have included ex-smokers; still others have estimated total deaths from all causes. To facilitate interstudy comparison, in some cases lung cancers had to be interpolated from a total, or the authors' original estimate had to be adjusted to include ex-smokers. Further, all estimates were adjusted to 1988. Excluding one study whose estimate differs from the mean of the others by two orders of magnitude, the remaining risk assessments are in remarkable agreement. The mean estimate is approximately 5000 +/- 2400 nonsmokers' lung cancer deaths (LCDSs) per year. This is a 25% greater risk to nonsmokers than is indoor radon, and is about 57 times greater than the combined estimated cancer risk from all the hazardous outdoor air pollutants currently regulated by the Environmental Protection Agency: airborne radionuclides, asbestos, arsenic, benzene, coke oven emissions, and vinyl chloride. PMID- 2184474 TI - Environmental tobacco smoke: exposure-response relationships in epidemiologic studies. AB - Demonstration of a dose-response relationship for environmental tobacco smoke (ETS) is an important indication of causality. Central to the analysis and interpretation of dose-response relations as described in epidemiological studies is the relationship between dose and exposure. It must be recognized that in studies of ETS we have only surrogate measures of dose, and these surrogate measures (based on exposure) are imperfect. The question-based measures of ETS exposure generally have not been standardized, may have limited validity and reliability, and cannot comprehensively describe total ETS exposure, exposure to individual ETS components, nor doses of biologically relevant agents at target sites. Nevertheless, useful data have been yielded in epidemiologic studies linking ETS exposure to increased respiratory infection and symptoms, reduced lung growth in children, and increased lung cancer in nonsmoking adults. The more consistent exposure-response data for studies on acute health in children may reflect the greater difficulty in measuring exposure in studies of chronic health in adults. PMID- 2184475 TI - Assessment of population exposure and carcinogenic risk posed by volatile organic compounds in indoor air. AB - A number of air pollutants are being found in low concentrations in indoor and outdoor air. Several studies have measured these concentrations for a large number of compounds in hundreds of residences. The concentrations range over several orders of magnitude over time and space. The log-normal distributions that are found make it possible to assess the impact on the health of populations, especially for genotoxic effects for which a threshold concentration is not expected to exist. Spreadsheets can be constructed which incorporate the unit risk of a substance for cancer, the distribution of concentrations of the substance in the population, and the size of the population into an assessment of the expected excess cases of cancer that can be attributed to the population exposure to such a toxicant. This approach allows for the evaluation of population risk for different substances as found in different environments, and for the evaluation of the relative efficacy of different strategies for population risk reduction. PMID- 2184476 TI - Review of radon and lung cancer risk. AB - Radon, a long-established cause of lung cancer in uranium and other underground miners, has recently emerged as a potentially important cause of lung cancer in the general population. The evidence for widespread exposure of the population to radon and the well-documented excess of lung cancer among underground miners exposed to radon decay products have raised concern that exposure to radon progeny might also be a cause of lung cancer in the general population. To date, epidemiological data on the lung cancer risk associated with environmental exposure to radon have been limited. Consequently, the lung cancer hazard posed by radon exposure in indoor air has been addressed primarily through risk estimation procedures. The quantitative risks of lung cancer have been estimated using exposure-response relations derived from the epidemiological investigations of uranium and other underground miners. We review five of the more informative studies of miners and recent risk projection models for excess lung cancer associated with radon. The principal models differ substantially in their underlying assumptions and consequently in the resulting risk projections. The resulting diversity illustrates the substantial uncertainty that remains concerning the most appropriate model of the temporal pattern of radon-related lung cancer. Animal experiments, further follow-up of the miner cohorts, and well designed epidemiological studies of indoor exposure should reduce this uncertainty. PMID- 2184477 TI - Quantitative cancer risk estimation for formaldehyde. AB - Of primary concern are irreversible effects, such as cancer induction, that formaldehyde exposure could have on human health. Dose-response data from human exposure situations would provide the most solid foundation for risk assessment, avoiding problematic extrapolations from the health effects seen in nonhuman species. However, epidemiologic studies of human formaldehyde exposure have provided little definitive information regarding dose-response. Reliance must consequently be placed on laboratory animal evidence. An impressive array of data points to significantly nonlinear relationships between rodent tumor incidence and administered dose, and between target tissue dose and administered dose (the latter for both rodents and Rhesus monkeys) following exposure to formaldehyde by inhalation. Disproportionately less formaldehyde binds covalently to the DNA of nasal respiratory epithelium at low than at high airborne concentrations. Use of this internal measure of delivered dose in analyses of rodent bioassay nasal tumor response yields multistage model estimates of low-dose risk, both point and upper bound, that are lower than equivalent estimates based upon airborne formaldehyde concentration. In addition, risk estimates obtained for Rhesus monkeys appear at least 10-fold lower than corresponding estimates for identically exposed Fischer-344 rats. PMID- 2184479 TI - [Development of the intra-vascular dye dilution detector using optical fiber catheter]. PMID- 2184478 TI - [Bladder endometriosis: review and presentation of 2 new cases]. AB - Two cases of vesical endometritis in two women aged 48 and a 46 years respectively are presented. Both cases were detected incidentally during a gynecological and vesical ultrasound study and the diagnosis was confirmed by cystoscopy and transurethral resection and histopathological exam. An exhaustive literature review is also presented and we insist on the rare presentation and the relatively specific clinical symptoms. A special note is made on the cystoscopic findings and on the different treatment techniques, including the latest approach with LH-RH analogues and/or transurethral photocoagulation with laser rays. PMID- 2184480 TI - [A case report of A-C bypass surgery in coronary atherosclerosis with anomalous origin of left coronary artery]. AB - Anomalous coronary artery originating from the aorta without complicated congenital cardiac anomaly is rare. We describe a case with the left coronary artery originating from the right sinus of Valsalva. Cardiac catheterization revealed a left coronary artery transverse between the aorta and the pulmonary artery. Severe atherosclerotic stenosis was present at segment 3 of the right coronary artery. Electrocardiogram and myocardial scintigraphy revealed that the angina occurred due to stenosis of the right coronary artery. We tried PTCA, but could not pass the catheter through the stenosis. After PTCA, he complained of anterior chest pain frequently, so we performed an aortocoronary bypass operation to the right coronary artery with saphenous vein graft. Postoperative course was not eventful and angina disappeared. PMID- 2184481 TI - [Subacute familial thalamic atrophy. Memory disorders and complete insomnia]. AB - Thalamic atrophy is rarely primitive. Selective atrophy of the dorso-medial and anterior thalamic nuclei has been reported in a few families. The clinical course is subacute. Symptoms and signs include sleep disorders and intellectual deficit. We report a new family with this uncommon disease and discuss its etiology. PMID- 2184482 TI - [Neurologic involvement in malignant mid-face granuloma]. AB - We report 4 cases with neurological disorders due to lethal centrofacial granulomas of unknown origin, and we review the relevant literature. This puzzling disease is characterized by a relentless ulceration of the nose progressing toward the base of the skull, and frequently involving the cranial nerves, the meninges and later the central nervous system. The main clinical point in such situations is to ascertain that no microorganism, no cancer, no specific disease is responsible for the centrofacial lesions, since the microscopic findings may be non-specific. When the entire work-up to exclude all differential diagnoses is completed, the clinician has to deal with lethal centrofacial granuloma. This seems to be a heterogeneous disease, in most of the cases close to malignant T lymphomas. Management is based on radiotherapy, chemotherapy and renutrition with treatment of frequent infectious complications. The prognosis is poor. PMID- 2184483 TI - [Large-cell intravascular malignant lymphoma]. AB - Neoplastic angioendotheliosis is a rare, severe, disease characterized by neoplastic proliferation of mononuclear cells within the lumen of small blood vessels. The clinical signs are usually dermatological and neurological. We report the case of a 57 year old woman who died after 20 months of subacute dementia. She had had also transient recurrent episodes of right paresthesiae and paresis. CSF proteins were increased. MRI showed areas of high signal in the white matter. Post-mortem showed widespread ischemic lesions, mainly in the subcortical white matter. Microscopically there was marked proliferation of cells in most CNS blood vessels. Similar cells were present in adrenals, liver, uterus, lungs and kidneys. Immunohistochemical studies showed intensive staining for leukocyte common antigen and negative staining for factor VIII-related antigen, a specific endothelial cell marker. PMID- 2184484 TI - [Prolonged remission in subacute sclerosing panencephalitis: 2 cases]. AB - Long survival in subacute sclerosing panencephalitis (SSPE), including total disappearance of clinical signs, is rare. Two cases are reported. They concern a girl and a boy who, at age 13 and 15, developed SSPE and are still in remission 6 and 5 years later. After a typical onset and course over periods of 12 and 18 months, clinical improvement was observed and periodic EEG complexes disappeared. However, the electrophoretic oligoclonal pattern of CSF proteins and the elevated measles titers persisted (in one case specific CSF IgM were still increased 6 years after the onset). MRI showed asymmetrical areas of high-intensity signal in both white and gray matter, predominant in the temporal, parietal and occipital regions. The age at which SSPE begins and the interval between measles and SSPE onset are not prognostic factors. On the other hand, in reported cases with lasting remission SSPE did not progress beyond Jabbour's stage II. The second typical feature of these long-term improvements is disappearance of EEG periodic complexes and emergence of a normal basic background activity. No other prognostic factor has been reported. PMID- 2184485 TI - [Multimodal evoked potentials in human immunodeficiency virus infection]. AB - We have studied 95 HIV seropositive patients (77 males and 18 females; mean age: 31 years): 67 had no neurological symptoms or signs, 28 had various neurological symptoms and signs. This study included a full multimodal evoked potentials (MEP) assessment: visual evoked potentials by flash and reversal checkerboard; brainstem auditory evoked potentials; somatosensory evoked potentials obtained by stimulation of the median nerve. Patient evaluation further included: electroencephalography, electromyography with measurement of conduction velocities and neuroimaging (brain CT scan and/or MRI). We found abnormal MEP for all modalities. The prevalence of abnormal results was high in neurological symptomatic patients; in non neurological ones, the changes tended to be more frequent with the progression of the HIV infection. Whatever the stage of the disease, the various modes were equally affected. MEP were abnormal in 54.7 p. 100 of the cases: in 41.8 p. 100 (28/67) of patient without neurological signs (in 4/12 of fully asymptomatic subjects, 11/34 ARC patients and 13/21 AIDS patients) vs 85.7 p. 100 of neurological symptomatic patients. In neurological asymptomatic patients, a similar proportion of abnormal MEP was found in asymptomatic and ARC patients, while the evolution into AIDS was associated with a higher prevalence of abnormal MEP. In the latter group, MEP changes were nearly as frequent as in neurological symptomatic patients. Comparison between MEP and other electrophysiological procedures (EEG, EMG) and with neuroimaging techniques (CT Scan, MRI) showed the high sensitivity of the MEP technique at all stages of the disease. EMG was a sensitive method and complementary to MEP. The EEG and neuroimaging techniques showed abnormalities principally at the neurological symptomatic stage. Previous studies could not be properly compared.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2184486 TI - [Neuroleptic malignant-like syndrome following levodopa withdrawal]. AB - The description of a syndrome similar to the neuroleptic malignant syndrome but occurring after levodopa withdrawal in a parkinsonian patient is reported. The imputation of levodopa withdrawal is analyzed according to the method of assessment of unexpected drug reactions used by the French centers of pharmacovigilance. This case is compared to 8 other published ones. PMID- 2184487 TI - [Intolerance to exercise caused by carnitine palmitoyltransferase deficiency]. AB - Exercise intolerance with slight myalgia worsened by a cold environment resulted in the diagnosis of CPT deficiency in a young boy with no family history. Recurrent myoglobinuria is not the hallmark of such a deficit. Biochemical examination of muscle biopsy in suggestive situations is the way to diagnosis. Concomitant myoadenylate deficiency in this patient could represent a precipitating factor. Partial CPT deficiency in all the patients reported was first explained through the mechanism of intra mitochondrial fatty acid transport but raises questions about the regulation of CPT synthesis. PMID- 2184488 TI - Daytime sleepiness, performance, mood, nocturnal sleep: the effect of benzodiazepine and caffeine on their relationship. AB - The present study was part of a larger 3-day, 2-night double-blind parallel group design in which 80 young adult men were divided into eight treatment groups to examine the effects of benzodiazepines and caffeine on nocturnal sleep and daytime sleepiness, performance, and mood. The present study was done to examine further the relationship among daytime sleepiness, performance, mood, and nocturnal sleep and to determine if and how these relationships were affected by the nighttime use of benzodiazepine and the ingestion of caffeine in the morning. Subjects received 15 or 30 mg of flurazepam, 0.25 or 0.50 mg of triazolam, or placebo at bedtime and 250 mg of caffeine or placebo in the morning for two treatment days. Two objective (Multiple Sleep Latency Test and lapses) and two subjective (Stanford Sleepiness Scale and Visual Analog Scale) measures of sleepiness, five performance tests, and two mood measures (Profile of Mood Scale and Visual Analog Scale) were administered repeatedly on both days. Electroencephalogram sleep was recorded on both nights. Objective sleep measures of daytime sleepiness were not significantly related to either performance or mood, but subjects with greater daytime sleepiness had significantly longer and more efficient nocturnal sleep. Neither benzodiazepine or caffeine influenced these relationships. In contrast, higher estimates of subjective sleepiness were significantly associated with poorer mood and tended to be related to poorer performance. Caffeine significantly reduced these relationships. Nocturnal sleep measures were not related to subjective estimates of daytime sleepiness. PMID- 2184489 TI - Preliminary findings in the treatment of obstructive sleep apnea with transtracheal oxygen. AB - The effects of continuous low flow oxygen via transtracheal oxygen delivery (TTOD) were assessed in four patients with obstructive sleep apnea (OSA) and daytime hypersomnolence who were unable to tolerate continuous positive nasal airway pressure (CPAP). The overall quality of sleep, sleep fragmentation, pattern of respiration, and nocturnal oxygen saturations were evaluated with the patients receiving 2 to 3 L/min of oxygen by TTOD, and the results were compared to polysomnograms with and without nasal cannula oxygen. The mean respiratory disturbance index (apneas plus hypopneas/hour of sleep) was improved by TTOD compared to no therapy or nasal cannula oxygen, and improvement in sleep disturbance was associated with improvement in overall nocturnal oxygen saturation. The mean apnea duration was not increased by TTOD and the duration of the longest apneic spells was decreased by 33 to 85% with this therapy. These improvements in respiratory status were accompanied by symptomatic improvement in daytime sleepiness, and there were no significant side effects. These findings suggest that TTOD may be a safe and effective alternative treatment of OSA for some patients who are unable to tolerate nasal CPAP therapy. PMID- 2184490 TI - Malignant external otitis: report on therapy with ceftazidime and review of therapy and prognosis. AB - We report the treatment of 20 patients with malignant external otitis (MEO) since 1980. Ceftazidime was used in 15 patients, with cure achieved in 11 of 12 evaluatable patients. An aminoglycoside and an antipseudomonal penicillin were used in five patients, four of whom were cured. The presentation, radiographic studies, therapy, outcome, and period of follow-up in the 20 patients are reported. The previously reported cases of MEO are also reviewed, with a focus on the changing therapy and prognosis. The frequencies of diabetes mellitus, cranial nerve deficits, and treatment failures in MEO have all declined significantly since 1985 from frequencies in earlier years. We conclude that there has been an overall improvement in the diagnosis and treatment of MEO and that monotherapy with ceftazidime shows promise against this potentially fatal pseudomonal infection. PMID- 2184491 TI - Cryptococcal skeletal infections: case report and review. AB - Cryptococcus neoformans is an uncommon but treatable cause of osteomyelitis that affects both normal and immunocompromised hosts. When not considered as a diagnostic possibility, C. neoformans infection may result in increased morbidity. The spectrum of disease at presentation extends from an asymptomatic patient with an osteolytic lesion on radiograph to a patient with signs and symptoms of systemic disease. Once diagnosis has been established (often by closed aspiration), optimal therapy appears to involve a combination of amphotericin B, flucytosine, and surgical debridement. PMID- 2184492 TI - On the obligation of physicians to treat AIDS: is there a historical basis? AB - This study examines the historical bases of what physicians ought to do as well as what they actually have done with regard to the treatment of diseases such as AIDS, which put them at risk for their lives. The earliest explicit statement of what ought to be done goes back only to 1847, when the American Medical Association was founded. However, this statement conflicts with a 75-year-old assertion that physicians have a right to choose whom they will serve. The conflict is compounded by the suspicion that both stated principles were based, at least in part, on socioeconomic considerations rather than moral imperatives. Of what physicians have actually done over the last 2,400 years, little more can definitely be said than that many have not tried to escape mortal risk while others have done so. Thus it is difficult to employ history as a basis for claiming that physicians have an obligation to treat AIDS. PMID- 2184493 TI - Musculoskeletal manifestations of infection with human immunodeficiency virus. AB - Musculoskeletal manifestations and autoimmune phenomena are recently recognized complications of infection with human immunodeficiency virus (HIV). Patients with HIV infection share several clinical and serologic features with patients with systemic lupus erythematosus and Sjogren's syndrome; these similarities may lead to diagnostic confusion. The significance of the presence of different types of autoantibodies in HIV-infected patients is still uncertain and may reflect polyclonal B cell activation. Musculoskeletal complications--particularly arthritis, arthralgia, and myalgia--are common in advanced stages of HIV infection. Clinical characteristics and serologic findings support the premise that most of the musculoskeletal complications (e.g., Reiter's syndrome, psoriatic arthritis, acquired immunodeficiency syndrome-associated arthritis and arthralgias) are reactive in nature--either a direct consequence of HIV infection or a result of various opportunistic infections. The possibility of HIV infection should be considered in all patients with conditions suggesting reactive arthritis. Further studies are needed to define the full spectrum and frequency of these musculoskeletal abnormalities. PMID- 2184495 TI - Review of recent pneumococcal infections with attention to vaccine and nonvaccine serotypes. AB - Conflicting data on the efficacy of the pneumococcal vaccine have continued to evolve. One important aspect of vaccine efficacy is related to the percentage of disease-causing serotypes contained in the vaccines. If disease-causing serotypes were to vary from place to place and population to population, vaccine efficacy would be variable and difficult to assess. We reviewed the literature on serotypic distribution of pneumococcal infection. Percentage of disease-causing serotypes covered by the 14-valent vaccine varied significantly from one study to another. Differences in age, hospital type, and source of isolation showed statistically significant serotypic distribution. PMID- 2184494 TI - Adverse antibiotic effects associated with renal insufficiency. AB - We review the English-language literature on antibiotic-associated adverse reactions in patients with renal insufficiency in order to highlight this important but often overlooked clinical problem. Because many adverse reactions to antibiotics are not dependent on renal function, we have attempted to review only those reactions that are believed to be associated with renal insufficiency or that have been reported in patients with impaired renal function. Adverse effects of antibiotics in this setting can be divided into six major categories: neurologic toxicity, coagulopathy, nephrotoxicity, hypoglycemia, hematologic toxicity, and aminoglycoside inactivation by penicillins. Neurologic toxicity can be further divided into central nervous system toxicity consisting primarily of encephalopathy and seizures, ototoxicity, peripheral neuropathy, and neuromuscular blockade/respiratory depression. We explore the factors in uremia that may contribute to the susceptibility of patients with renal insufficiency to the adverse effects of antibiotics. Moreover, we make general recommendations regarding the use of the discussed antibiotics in patients with compromised renal function. PMID- 2184496 TI - Postpartum maternal group B streptococcal meningitis. AB - Maternal group B streptococcal (GBS) meningitis is rare, with only four cases previously reported in the literature. In this review a fifth case of postpartum GBS meningitis is presented. The five cases are compared with 34 cases of GBS meningitis in nonparturient adults. All cases of maternal GBS meningitis followed a vaginal delivery. The mean age of patients who had GBS meningitis outside the perinatal setting was 55 years, and most of these individuals had associated illnesses or frank immunosuppression; the mortality rate in this group was 23%. In contrast, all five patients with maternal GBS meningitis recovered. The case presented herein, like the four previous cases, illustrates the point that when patients with maternal GBS meningitis are treated immediately and have been healthy before the infection, the prognosis is good. PMID- 2184497 TI - Invasive external otitis caused by Aspergillus. AB - Invasive external otitis occurs almost exclusively in patients with longstanding diabetes. Except for occasional cases, the etiologic agent has been Pseudomonas aeruginosa. We report a case caused by Aspergillus species in a diabetic patient with acute leukemia. Persistent infection was documented by culture and histology after a course of intravenous amphotericin B (total dose, 2 g). Clinical resolution occurred in association with a 3-month course of oral itraconazole. Four previously reported cases of invasive aspergillus otitis are reviewed. PMID- 2184498 TI - Acute appendicitis complicating infectious mononucleosis: case report and review. AB - Acute appendicitis is an uncommon complication of infectious mononucleosis (IM) and can readily be misdiagnosed because of the acute abdominal pain with which patients with IM occasionally present. A case report is presented of a patient with IM who developed acute appendicitis during the acute phase of the illness. The appendicitis progressed to the formation of an abscess, which was evacuated at surgery. Histologic examination of the appendix showed absence of lymphoid follicles in the mucosal layer and intense lymphoid infiltration of the mucosa and submucosa by a mixed diffuse proliferation of lymphoid cells with groups of immunoblasts scattered among them. The lymphoid infiltrate was mainly composed of T lymphocytes; the anticomplementary immunofluorescent staining of the appendix for EBNA (Epstein-Barr nuclear antigen) was negative. Three cases of appendicitis complicating IM published in the literature are reviewed. All had clinical and histopathologic features similar to those of our patient and were cured after surgery. Our case report together with the literature review confirms that appendicitis in the acute phase of IM has distinct clinical and histopathologic features and thus has to be considered a true complication of IM rather than merely a simultaneous disease. PMID- 2184499 TI - Amphotericin B: 30 years of clinical experience. AB - Amphotericin B, the first commercially significant antifungal drug, has been available for more than 30 years. This polyene macrolide antifungal agent continues to play a major role in the treatment of systemic fungal infections, despite the introduction of newer agents such as the azoles. Given the proved efficacy of amphotericin B--and the increasing number of indications for antifungal agents--an extensive review of this drug is warranted. This paper discusses the clinical uses of amphotericin B, including its application in AIDS related fungal infections, in neutropenic cancer patients who are persistently febrile, and in infections of the central nervous system, lung, peritoneum, genitourinary system, eye, and skin. The paper also reviews the drug's adverse reactions, with a discussion of administration techniques that may reduce these reactions, and its spectrum of activity, pharmacokinetics, and dosage and administration. PMID- 2184500 TI - Ultrasonography in the diagnosis and management of 52 patients with amebic liver abscess in Cairo. AB - Clinical characteristics of 52 patients with amebic liver abscess are reported. Forty-two percent had an acute illness, usually with high fever, vomiting, sweating, pain in the abdominal right upper quadrant, and leukocytosis. The other 58% had a more chronic illness, usually with a dull ache in the right upper abdomen, weight loss, fatigue, moderate or low-grade pyrexia, and anemia. Hepatomegaly and hepatic tenderness were present in all patients; fever occurred in 75%. The diagnosis was strongly suggested by amebic antibodies in high titer and hepatic abscesses demonstrated by sonography. Mean abscess diameter was 9.2 cm; 37% were larger than 10 cm. Most abscesses were solitary (81%), in the right lobe (73%), rounded or oval (78%), cystic (57%), and had a well-defined wall (53%). However, 43% were initially solid or heterogeneous. The latter lesions always developed a cystic pattern when ultrasonography was repeated. The diagnosis was confirmed by a good clinical response to metronidazole in 50 patients. Complications included right-sided pleural effusions or empyema (13%), ascites (13%), and jaundice (13%). Drainage of large abscesses was performed in four patients. All 52 patients survived and were cured. PMID- 2184501 TI - The microbe of pleuropneumonia. 1896. PMID- 2184502 TI - Implications of the inoculum effect. PMID- 2184503 TI - Discovery of fluconazole, a novel antifungal agent. AB - Fluconazole, 2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)-2-propanol, is the result of a research program aimed at the development of a broad-spectrum antifungal agent active by both the oral and the intravenous routes for the treatment of superficial and systemic infections. The program began in 1978, and azole derivatives were chosen as a starting point because they were generally well tolerated and offered the advantage of a selective mode of action- inhibition of fungal sterol C-14 demethylation. Initial investigations focused on imidazole derivatives, but attention soon switched to triazole analogues because of their reduced susceptibility to metabolic activity. Polar derivatives were emphasized in an effort to facilitate the attainment of high levels in the blood and to reduce metabolic breakdown still further. This strategy resulted in a number of novel 1,3-bis-triazole-2-arylpropan-2-ol derivatives with good activity in a range of models of fungal infection. These models included systemic fungal infections in both normal and immunosuppressed animals and superficial infections in animals with normal immune function. The 2,4-difluorophenyl analogue, fluconazole, was chosen for development on the basis of an optimal combination of antifungal efficacy, pharmacokinetic characteristics, aqueous solubility, and safety profile. PMID- 2184504 TI - Susceptibility of Candida albicans and other yeasts to fluconazole: relation between in vitro and in vivo studies. AB - In vitro studies of fluconazole have demonstrated that test results can be influenced by several test conditions, including medium composition, pH, and size of the starting fungal inoculum. In studies with Candida albicans, a few isolates have been identified that are markedly more resistant than other strains of the same species; in several in vivo studies of experimental infections, the more resistant isolates have caused infections less susceptible to fluconazole treatment. These findings corroborate a relation between in vitro and in vivo results. With further work it should be possible to define standard methods for use by clinical laboratories in determining fungal susceptibility to fluconazole. PMID- 2184505 TI - Fluconazole and other azoles: translation of in vitro activity to in vivo and clinical efficacy. AB - Fluconazole is polar, soluble in water, and metabolically stable and exhibits low protein binding. In contrast, other systemic azoles are lipophilic, metabolically vulnerable compounds with high protein binding and negligible solubility in water. The physical and pharmacokinetic properties of these drugs plus their inherent antifungal potency determine their efficacy. Although fluconazole is less active than ketoconazole in vitro, its distribution throughout the body and the high levels of free drug reached in the blood contribute to and are of value in predicting its efficacy. Even for ketoconazole the levels of free drug in blood may be indicative of efficacy. For very lipophilic agents (itraconazole), blood levels of drug are very low, and organ levels may correlate better with efficacy, although tissue binding will be high and total drug levels in an organ may be misleading indicators of efficacy. The excellent efficacy of fluconazole in vivo despite its low activity in vitro has caused confusion. Consequently, a disk test is being developed to assess whether fungal isolates are sensitive to therapeutically achievable levels of drug. PMID- 2184506 TI - Efficacy of fluconazole in experimental invasive aspergillosis. AB - The efficacy of fluconazole against Aspergillus fumigatus was evaluated in an immunosuppressed, temporarily leukopenic rabbit model of invasive aspergillosis. Fluconazole was given at a dosage of 60 mg/kg twice daily and was compared with amphotericin B given intravenously at a dosage of 1.5 mg/(kg.d). Fluconazole reduced the tissue burden of Aspergillus from that in untreated controls by 10- to 100-fold in liver, kidney, and lung. However, at these doses amphotericin B was more effective in sterilizing tissues and in reducing the tissue burden of Aspergillus in those organs. Both fluconazole and amphotericin B decreased or eliminated circulating Aspergillus antigen and improved survival over that of untreated controls. Thus fluconazole shows activity in this rabbit model of invasive aspergillosis and should be further evaluated for use in the treatment of this disease. PMID- 2184507 TI - Efficacy of fluconazole in prophylaxis and treatment of experimental Candida endocarditis. AB - The efficacy of fluconazole, a bis-triazole antifungal agent, for prophylaxis and treatment of endocarditis due to Candida albicans and Candida parapsilosis is assessed in a rabbit model. Fourteen daily injections of fluconazole at doses of 20 and 10 mg/kg of body weight eradicated C. albicans and C. parapsilosis, respectively, from the cardiac vegetations in all animals tested. Amphotericin B (3 mg/kg) and flucytosine (35 mg/kg) both singly and in combination failed to achieve eradication in 100% of the animals. A two-dose prophylactic regimen of 30 mg of fluconazole/kg was consistently successful in preventing experimental endocarditis caused by C. albicans or C. parapsilosis. PMID- 2184508 TI - Fluconazole therapy for experimental cryptococcosis and candidiasis in the rabbit. AB - Fluconazole is a second-generation azole compound with broad-spectrum antifungal activity. It has been examined in several animal models emphasizing important clinical sites of infection with common yeast pathogens. The drug has an excellent pharmacokinetic profile for central nervous system, renal, and ocular infections; at these sites fluconazole has been successful in the treatment of infections with Cryptococcus neoformans or Candida albicans. On the basis of the experience in animals, fluconazole should be critically evaluated in the treatment of human mycoses such as cryptococcosis of the central nervous system and renal/ocular candidiasis. This agent represents the new wave of interest in the increasingly troublesome problem of deep-seated fungal infections. PMID- 2184509 TI - Experimental basis for use of fluconazole for preventive or early treatment of disseminated candidiasis in granulocytopenic hosts. AB - To determine the potential for the use of fluconazole for prevention and treatment of disseminated candidiasis in granulocytopenic patients, we investigated its activity and pharmacokinetics in models of acute, subacute, and chronic forms of disseminated candidiasis in persistently granulocytopenic rabbits. Fluconazole was administered for systemic prophylaxis, early treatment, and delayed treatment. Single-dose and steady-state plasma pharmacokinetics, tissue penetration, and dose-response studies of the investigational compound were studied in subacutely infected granulocytopenic rabbits. Fluconazole was more effective when used for systemic prophylaxis or early treatment of disseminated candidiasis than for delayed treatment. Fluconazole was as effective as amphotericin B plus flucytosine in preventive and early treatment of disseminated candidiasis but was significantly less effective than amphotericin plus flucytosine in the treatment of chronic candidiasis. Dose-response studies demonstrated that the antifungal effect of fluconazole was dose- and time dependent. Studies of the pharmacokinetics of fluconazole in rabbits demonstrated a long half-life in plasma and a large volume of distribution, properties that correspond to the attainment of high levels of penetration into tissues at multiple organ sites. We conclude that fluconazole is effective for prevention and early treatment of disseminated candidiasis in persistently granulocytopenic rabbits and that the evaluation of its use in preventive or early treatment of disseminated candidiasis in carefully designed clinical trials is warranted. PMID- 2184511 TI - Overview of studies of fluconazole in oropharyngeal candidiasis. AB - Studies with fluconazole in oropharyngeal candidiasis have focused primarily on three groups of infections: chronic atrophic candidiasis, oropharyngeal infections associated with either neutropenia or AIDS, and chronic mucocutaneous candidiasis. In two studies of chronic atrophic candidiasis associated with dentures, 82 patients received 7 or 14 days of therapy with fluconazole (50 mg daily). Clinical and mycologic cure rates ranged from 69% to 100%, with the best results occurring with 14 days of therapy in combination with the cleansing of dentures. Thirteen patients with oroesophageal candidiasis associated with chronic mucocutaneous candidiasis were treated with 50 or 200 mg of fluconazole daily, and clinical and mycologic remissions were achieved in a mean period of 10 days. So far 95 patients have been treated with fluconazole for oropharyngeal candidiasis associated with malignancy, therapeutic immunosuppression, AIDS, or AIDS-related complex. Infection was cured by clinical criteria in 84% of those studied. While the majority of patients with clinical cure had significant reductions in the number of yeast colonies, only 48% had negative oral cultures at the end of therapy with courses of 50 mg of fluconazole daily for 5 days to 8 weeks. PMID- 2184510 TI - Pharmacokinetics and tissue penetration of fluconazole in humans. AB - The pharmacokinetics and tissue/fluid penetration of fluconazole have been studied in more than 400 healthy individuals and various subsets of patients. The pharmacokinetics of fluconazole are similar following intravenous and oral dosing. Oral bioavailability is greater than 90%, and concentrations peak approximately 2 hours after dosing. The apparent volume of distribution is 0.7 L/kg, and plasma protein binding is low (12%). The drug is metabolically stable, with renal excretion accounting for approximately 80% of the elimination as unchanged drug. Repeated once-daily dosing results in an increase in plasma levels of approximately 2.5-fold, with steady state achieved by day 7. Plasma levels are dose-proportional, and the elimination rate remains constant across the dosage range and over time. The plasma half-life of fluconazole is approximately 30 hours. The pharmacokinetics are similar in healthy young adults and in the elderly, but dose modification is required in patients with renal impairment. Fluconazole diffuses readily into the cerebrospinal fluid, sputum, and saliva and is concentrated in the urine and skin. PMID- 2184512 TI - Overview: treatment of cryptococcal meningitis. AB - Infections caused by Cryptococcus neoformans cause significant morbidity and high mortality, particularly among immunocompromised patients. Cryptococcal meningitis is an important cause of central nervous system disease and death in patients with AIDS. Although the introduction of amphotericin B has greatly improved the prognosis of patients with cryptococcal meningitis, 30 years of experience have revealed important clinical limitations, including modest efficacy, nephrotoxicity, other clinically significant toxicities, and the inconvenience of intravenous dosing. The discovery of the additive effects of amphotericin B and flucytosine in cryptococcosis resulted in some improvement in efficacy and reduction in amphotericin B-related toxicity. However, approximately 30% of patients with cryptococcal meningitis still fail to respond to therapy. Ketoconazole has not proved useful in treating cryptococcal meningitis. Accumulating evidence suggests that the antifungal triazoles fluconazole, itraconazole, and SCH 39304 represent an advance in the treatment of cryptococcal meningitis, particularly in AIDS patients. Preliminary clinical trials in patients with and without AIDS have indicated that fluconazole and intraconazole are effective and well tolerated as either initial or maintenance therapy. Two large comparative trials of fluconazole and amphotericin B in patients with cryptococcal meningitis (mostly those with AIDS) are under way. PMID- 2184513 TI - Therapy for oropharyngeal candidiasis in the immunocompromised host: a randomized double-blind study of fluconazole vs. ketoconazole. AB - Optimal therapy for oropharyngeal candidiasis, a common infection in immunocompromised patients, has yet to be clearly defined. Topical therapy is usually poorly tolerated; ketoconazole is effective but absorption is highly variable. New antifungal agents have been developed to increase the therapeutic options. Fluconazole is active against yeasts, is available in both oral and intravenous formulations, and has a pharmacokinetic profile different from that of ketoconazole. This randomized double-blind study evaluates systemic antifungal therapy with fluconazole (100 mg daily) or ketoconazole (400-mg daily) for oropharyngeal candidiasis in patients with cancer. Clinical cure was observed in 15 of 19 and 14 of 18 patients treated with fluconazole and ketoconazole, respectively. Eradication of pathogenic yeasts ws documented for 10 patients in both groups. The rates of relapse were similar, but relapse occurred earlier in patients in the ketoconazole group. Overall, this study demonstrates the value of a dosage of 100 mg of fluconazole or of 400 mg of ketoconazole daily for the management of oropharyngeal candidiasis in patients with cancer. PMID- 2184514 TI - Prophylaxis of oropharyngeal candidiasis with fluconazole. AB - A total of 112 cancer patients who could ultimately be evaluated were randomly assigned in a double-blind study to receive either fluconazole or placebo as antifungal prophylaxis during hospitalization. Thrush, defined by appropriate lesions in the oropharynx and confirmed by scrapings and cultures positive for Candida species, occurred in 2% of the 58 patients given fluconazole and in 28% of the 54 patients given placebo (P = .0003). Candida species were cultured from initial throat specimens from 29 patients given fluconazole and from 26 patients given placebo. Oropharyngeal candidiasis was detected subsequently in 3% of the former patients and 54% of the latter patients (P = .0001). Adverse reactions that were probably due to or aggravated by fluconazole occurred in only four patients and consisted of transient liver function abnormalities in three instances and nausea and vomiting in one. Oral fluconazole is an effective agent for prophylaxis of oropharyngeal candidiasis in susceptible cancer patients. PMID- 2184515 TI - Antifungal prophylaxis in bone marrow transplantation. AB - Deep fungal infection in recipients of bone marrow transplants remains a significant cause of morbidity and mortality. Prolonged neutropenia is the major factor predisposing patients to invasive fungal disease. Candida and Aspergillus species remain the two most common pathogens. Prophylaxis against these organisms with the oral polyenes nystatin and amphotericin B has been disappointing. Systemic amphotericin B is too toxic for prophylactic use, yet it remains the mainstay of therapy for suspected or established deep fungal infection. Ketoconazole is contraindicated in patients receiving cyclosporine prophylaxis against graft-vs.-host disease and appears effective only in high doses associated relatively commonly with adverse reactions. This paper reviews results of antifungal prophylaxis and discusses new measures and agents likely to be of value in the prevention of fungal infection in bone marrow transplantation. PMID- 2184516 TI - [Malignant atrophic papulosis (Degos' syndrome)]. AB - In a 49-year-old female patient with an eruption of lentil-shaped papules on the trunk and extremities, persisting for six years, originally in another department scleroderma guttata was diagnosed. For one year the patient suffered also from dyspeptic complaints, loss of weight and relapsing polyserositis. The complaints receded temporarily after immunosuppressive therapy. On surgical revision of the abdominal cavity on account of serous peritonitis during the last three months eruption of whitish foci on the intestinal serosa and omentum was found. Bioptic excision of the skin revealed an old bland infarct. From the clinical course and dermatological picture papulosis maligna atrophicans (Degos' syndrome) was diagnosed. Autoptic examination confirmed the clinical diagnosis of the syndrome by the finding of thromangiitis of Burger's type with bland infarcts of the small intestine and perforation of the jejunum. PMID- 2184517 TI - Kaposi's sarcoma puzzle begins to yield. PMID- 2184518 TI - Production of radionuclides for medicine. AB - Naturally occurring, nuclear reactor-produced, cyclotron-produced, and generator produced radionuclides are reviewed with special reference to nuclear medical and biological use. General methods of labeling, and 99mTc, 131I, 125I, 123I, 11C, 13N, 15O, 3H, and 14C labeling methods are described. PMID- 2184519 TI - Radiopharmaceuticals for imaging myocardial perfusion. AB - A replacement for 201Tl used in myocardial perfusion imaging with a 99mTc-labeled complex is a long-sought goal. Now, at least three varieties of 99mTc-complexes are being made available for clinical studies. This review summarizes the development of these agents and presents basic research data accumulated in this area. Also, relevant clinical radiopharmaceutical protocols and relative merits of competing 99mTc-agents are discussed. PMID- 2184520 TI - Radioiodinated tracers for myocardial imaging. AB - Recent advances in the efficient production of high purity radioiodine (123I) and new efficient radiolabeling techniques have allowed the development of new classes of cardiovascular radiopharmaceuticals. These include 123I-labeled fatty acids to assess myocardial metabolism, 123I-metaiodobenzylguanidine (MIBG) for myocardial neuronal activity, labeled monoclonal antibodies for myocardial necrosis, and labeled lipoproteins for receptor concentration. 123I-labeled fatty acids and MIBG are under clinical investigation with encouraging results. 123I- and 111In-labeled fragments of monoclonal antibodies to myosin have been used for imaging myocardial necrosis in humans. The development of radiotracers for imaging of cholinergic and adrenergic receptors is still in the experimental stage. Recent advances in imaging instrumentation and radiopharmaceuticals have resulted in cardiac imaging applications beyond blood pool ventriculography, perfusion, and infarct-avid imaging. Developments of radioiodine (123I)-labeled agents promise to play an important role in the assessment of myocardial metabolism, neuronal activity, and receptor concentration. The chemistry of iodine is well defined compared with that of 99mTc; therefore, iodine isotopes are well suited for labeling biologically important molecules. Among the iodine isotopes, 123I has nearly ideal nuclear properties for nuclear medical applications with a 13.3-hour half-life (T1/2) and 159 keV gamma emission (83%). Despite the nearly ideal chemical and nuclear properties of 123I, the widespread application of 123I-based radiopharmaceuticals in clinical practice has been limited by high production costs (123I is produced in a cyclotron), relatively limited availability, and the presence of undesirable radionuclidic impurities (124I, T1/2 = 4.2 days; 125I, T1/2 = 60 days; 126I, T1/2 = 13.1 days). The relatively long T1/2 and beta particle emission can substantially increase the higher radiation burden to the patient. High energy gamma rays (greater than 600 KeV) from these impurities can degrade images obtained using low energy collimators. Recent developments in production techniques have greatly reduced the levels of the undesirable radionuclides in 123I. Ready availability of pure 123I at modest cost, in concentrations suitable for the radio-labeling of a variety of useful biomolecules, should enhance the clinical applications of 123I labeled compounds. Molecules labeled with 123I that are useful in cardiac imaging studies are fatty acid analogs, monoclonal antibodies, receptor binding agents, and norepinephrine analogs. This article will discuss developments in radioiodine (123I)-labeled radiotracers for myocardial imaging. PMID- 2184521 TI - Pharmacokinetics and clinical application of technetium 99m-labeled hepatobiliary agents. AB - Hepatobiliary imaging, introduced first in late 1950s with iodine 131 rose bengal, has undergone major changes since the introduction of technetium 99m labeled agents in the late 1970s. 99mTc-labeled iminodiacetic acid (IDA) agents, with their high hepatic uptake and fast biliary excretion, provide superior image resolution in addition to supplying simultaneous physiologic parameters quantitatively. The measurement of hepatic extraction fraction by deconvolutional analysis aids in separating hepatocyte from biliary disease. Excretion half-time calculation by nonlinear least square fit provides a quantitative method of analyzing hepatobiliary function and correlates directly with the severity of disease. The measurement of gallbladder ejection fraction, ejection rate, and common bile duct bile reflux index following cholecystokinin, enables quantification of the degree of obstruction to bile flow through the common bile duct. The combined application of morphologic and physiologic parameters enables diagnosis of various hepatobiliary disease, especially in early stages. Quantitative functional parameters not only provide criteria for diagnosis, but also assist in monitoring the therapeutic benefit from drugs and interventional techniques such as endoscopic sphincterotomy or balloon dilation of the obstruction. Biliary dynamic studies with cholecystokinin assist in distinguishing common bile duct dilation without obstruction from dilation with obstruction. Methods of application of 99mTc-IDA agents in quantitative physiologic studies are reviewed and future direction of their use is proposed. PMID- 2184522 TI - New technetium 99m-labeled brain perfusion imaging agents. AB - In developing new brain perfusion imaging agents, three types of neutral and lipid-soluble technetium 99m complexes have been reported: 99mTc-ethylene cysteinate dimer, 99mTc-hexamethyl propylene amine oxime, and 99mTc-boric acid adduct of technetium oxime. Structure-activity relationships of these complexes on brain uptake and retention have been investigated. The new 99mTc-brain perfusion imaging agents are useful in detecting various cerebral vascular abnormalities. The exact trapping mechanisms and their relationship with potential clinical applications still remain to be elucidated. However, initial clinical studies with 99mTc agents do show parallel clinical efficacy as those reported for the iodine 123-labeled brain perfusion agents, isopropyliodoamphetamine and N,N,N'-trimethyl-N'-[2-hydroxy-3-methyl-5 iodobenzyl]-1,3-propanediamine . PMID- 2184523 TI - Testicular scanning and other applications of radionuclide imaging of the genital tract. AB - The major application of nuclear imaging techniques to the genital tract is pertechnetate scintigraphy for evaluation of the acute hemiscrotum. Within a few years of the first descriptions of scrotal imaging, this technique achieved recognition as a valuable, even indispensable, emergency diagnostic procedure in this context; its validity has since been well confirmed in hundreds of reported cases. Because it is an established procedure with widely recognized applications, its discussion will occupy most of this article. Other nuclear procedures, less widely used either because they are investigative or applicable to smaller patient populations, will be more briefly described. PMID- 2184524 TI - Radiochemistry: a current status report II. Festschrift to L. Rao Chervu, PhD and Shanta Chervu, MD. PMID- 2184525 TI - [Antibodies against human immunodeficiency virus in generalized lupus erythematosus]. AB - After studying a bisexual male with a clinical picture suggestive of AIDS a positive ELISA test for antibodies against the Human Immunodeficiency Virus (HIV), but negative results on indirect immunofluorescence testing, as well, as absence of core and envelope HIV antibodies by ELISA, and who later turned out to have Systemic Lupus Erythematosus (SLE) which become asymptomatic on corticosteroid therapy, we decided to test 70 patients with SLE for HIV antibodies. Four of them (5.6%) were positive by ELISA, but on a repeated test only 2 (2.8%) remained positive, and their sera was tested by indirect immunofluorescence. They were negative, as was the ELISA test for core and envelope HIV antibodies. We conclude that the possibility of more such cases, of SLE mimicking AIDS, should be kept in mind, including the occurrence of false positive ELISA tests in such patients. PMID- 2184526 TI - [Nutritional status in children under 6 years of age and its relation to malaria and intestinal parasitism]. AB - In order to determine the prevalence of the nutritional situation in children under six years of age and to study the relation with malaria and intestinal parasitism an epidemiological study of a cross sectional was carried out in Cordoba locality, Buenaventura Municipality in the Colombian Pacific Coast. One hundred and twenty eight children were studied to whom a questionnaire, a thick smear examination, and a serological test through the indirect immunofluorescence reaction was practiced. Coproparasitoscopic examination were also done in addition to medical and clinical anthropometric examinations, the latter consisting of the measurements of weight and height. The results of this investigation showed a prevalence of the nutritional state, according to Waterlow classification, of 0.81 percent, 17 percent and 2 percent for the first, second and third degree of malnutrition respectively. Instead, according to the Gomez classification it was 49 percent, 14 percent and 2 percent for the slight, moderate and severe degrees of malnutrition. When the geometric mean of the antibody titles for P. falciparum and for P. vivax were compared, using the methodology of the Waterlow classification, statistical associations were discovered and it was found that the geometric mean for P. falciparum were higher in those children that didn't have any malnutrition. Nevertheless, the geometric mean for P. vivax was higher for those children with a certain degree of malnutrition. Nevertheless, when the intensity of infection of the intestinal helminths, the quality of the dwelling and the breast-fed time duration were compared, no significant differences were detected, therefore we believe it convenient to keep on with this type of investigation, specially with those longitudinal-type studies so as to detect causal association in the relation nutrition/malaria. PMID- 2184527 TI - Short-course chemotherapy for pulmonary tuberculosis with a rifampicin-isoniazid pyrazinamide combination tablet. AB - The effectiveness of a tablet containing a combination of rifampicin, isoniazid and pyrazinamide (Rifater; Mer-National) in the treatment of pulmonary tuberculosis was examined by comparing it with a previously evaluated four-drug regimen. Of 150 black goldminers with a first case of pulmonary tuberculosis, 69 were randomly allocated to receive the combination tablet (RHZ), 5 tablets per day on weekdays for 100 treatment-days, and 81 the four-drug regimen (streptomycin, rifampicin, isoniazid and pyrazinamide) (RHZS). Non-compliance was detected in 42% of the RHZ group and in 16% of the RHZS group. Two patients in the RHZ group and 4 in the RHZS group had to have their treatment altered because routine investigations revealed drug-resistant mycobacteria. Treatment was unsuccessful in 10 patients in the RHZ group, with 4 men failing to complete the regimen and being lost to follow-up, 3 cases of failure of conversion of sputum on the regimen, and 3 relapses. The results for the RHZS group were similar, with 4 failures to complete the regimen, 2 treatment failures and 4 relapses. Evaluation of RHZ showed it to be comparable with a previously evaluated, successful short-course regimen (RHZS). The high incidence of non-compliance probably reflects reduced supervision of this wholly oral regimen. PMID- 2184529 TI - Death due to anaesthesia at Groote Schuur Hospital, Cape Town--1956-1987. Part I. Incidence. AB - The data from a 30-year surveillance study of anaesthetic mortality associated with 0.75 million anaesthetics administered at Groote Schuur Hospital, Cape Town, from 1956 to 1987 are presented. Behind an overall mortality rate of 0.19 deaths per 1,000 anaesthetics attributable to anaesthesia, lies a 6-fold decrease in the incidence, computed quinquennially, from 0.43 per 1,000 anaesthetics in the first quinquennium to 0.07 per 1,000 anaesthetics in the last. The latter figure portrays a standard of safety in anaesthesia for the patient equal to anywhere in the world. PMID- 2184528 TI - An evaluation of two indirect fluorescent antibody tests for the diagnosis of Legionnaire's disease in South Africa. AB - The specificity and sensitivity of the indirect fluorescent antibody test (IFA) for the diagnosis of Legionnaires' disease in South African patients is unknown. Heat-treated and formalin-treated antigen preparations from 456 normal blood transfusion donors and from 34 confirmed patients with the disease (3 culture positive cases and 31 cases of seroconversion) were assessed. Tests using both antigens showed a relatively high degree of positivity at low titres in normal individuals with an age-related increasing frequency of positive tests. The best combinations of specificity and sensitivity of the heat-treated antigen determinations were at titres of 1/128 and for formalin-treated antigen at titres of 1/8 for both IgG and IgM. An IgM titre of 1/8 using the formalin-treated antigen appeared to be the best diagnostic criterion of the IFA but an antibody level of 1/8 using this antigen was attained in only 37.1% of cases on initial testing but 100% of cases on subsequent testing. PMID- 2184530 TI - Death due to anaesthesia at Groote Schuur Hospital, Cape Town--1956-1987. Part II. Causes and changes in aetiological pattern of anaesthetic-contributory death. AB - A general analysis of the clinical failures that were responsible for deaths attributable to anaesthesia over a 30-year period, 1956-1987, is presented. Four particular general failures in clinical management were responsible for 80% of anaesthetic-contributory deaths (ACD). These were in descending order of frequency: (i) failures in airway management, of which the majority were associated with the complications of endotracheal intubation (27% of ACD); (ii) failures in pulmonary ventilation management (20% of ACD); (iii) failures in blood volume control (19% of ACD); and (iv) failures in arrhythmia control (17% of ACD). Computation of these groups of causes by the decade reveals a distinct and progressive change in the aetiological pattern of these deaths with time. While the incidence of ACD over the period decreased 6-fold from 0.43 to 0.07/1,000 anaesthetics, that proportion due to failures in airway management, in general, and complications of intubation, in particular, has progressively increased. This has been accompanied by a reciprocal decrease in deaths due to circulatory factors. It is postulated that this change arises from the fact that the physical skills, manual dexterity and clinical judgement demanded by the former have not changed with time, whereas the latter depend on intellectual responses to information derived from ever-improving vital function monitoring. PMID- 2184531 TI - Familial medulloblastoma in siblings: report in one family and review of the literature. AB - Two siblings in a family--a 5-year-old boy and an 8-year-old girl--suffered from progressive headache and gait disturbance in an interval of 1 year, consecutively. Neurologic manifestations were papilledema and truncal ataxia. Both of their computed tomography scans showed a large, well-enhanced tumor located in the cerebellar vermis with secondary hydrocephalus. Both had surgical resection followed by craniospinal irradiation and then chemotherapy. The pathologic findings confirmed the diagnosis of medulloblastomas. The family pedigree disclosed some other cancer in close relatives. These findings suggested a possible role of heredity in the oncogenesis of this tumor. To our knowledge, our cases are the seventh report of familial medulloblastoma occurring in nontwin siblings in the world. PMID- 2184532 TI - What is the role of the eosinophil? PMID- 2184533 TI - Tobacco and the Third World. PMID- 2184534 TI - Potassium channels and airway function: new therapeutic prospects. PMID- 2184535 TI - AIDS and the lung. 7. Treatment of lung disease in patients with the acquired immune deficiency syndrome. PMID- 2184537 TI - [Better decisions--but how?]. PMID- 2184538 TI - [Development of a computer program for early diagnosis of acute myocardial infarction]. AB - A standardised case history was obtained for 1,163 patients admitted to the Central Hospital of Akershus due to suspected acute myocardial infarction. From this database, a computer program was developed for establishing early diagnosis of acute myocardial infarction. In a given patient the program calculates the probabilities of the different conditions giving rise to the particular chest pain history by applying Baye's conditional probability approach. The program proved valuable as a supportive clinical tool of decision in patients admitted with acute chest pain. PMID- 2184539 TI - [Testing of a computer program model for the diagnosis of suspected acute coronary disease]. AB - A computerized diagnostic system to be used in patients with acute chest pain was recently developed in our department, and was tested prospectively in 213 consecutive patients with acute chest pain. In our study, the computer system almost invariably improved the decision as to whether or not admission to the coronary care unit was necessary. Thus, compared with decisions made by the emergency room physicians the computer system would have reduced by approximately 75% the number of patients with acute myocardial infarction who are incorrectly referred to the general ward. The system would also have reduced by the same figure the number of cases wrongly placed in the coronary care unit. Thus, in patients admitted with acute chest pain, the use of our computerized system would have improved both diagnostic accuracy and correct referral of patients from the emergency room. PMID- 2184536 TI - Molecular biology and respiratory disease. 3. Evaluation of nucleolar organiser regions in pulmonary pathology. PMID- 2184540 TI - [Identification of syndromes using a combined computer and video program]. AB - The use of the database POSSUM (Pictures of Standard Syndromes and Undiagnosed Malformations) was evaluated over a period of 1 1/2 years in 49 children with multiple congenital anomalies. A specific diagnosis was obtained in 23 cases and POSSUM contributed significantly to a diagnosis in 13 cases. We conclude that a computerized approach is valuable in the evaluation of dysmorphic syndromes. PMID- 2184541 TI - [Ultrasonic diagnosis of the upper abdomen performed in general practice]. AB - This paper considers the use of ultrasound diagnostics performed by a general practitioner on patients with pain in the upper abdominal region, with particular attention to the liver, gallbladder and aorta. 189 patients were examined, of whom 48 were found to have one or more diseases. 55 specific diagnoses were made. 23 patients had gallstones, and five had aortic aneurysm. Malignant diseases were suspected in five patients. The negative results were evaluated by means of a questionnaire after completion of the period of registration. This questionnaire did not expose any undiagnosed disease in the examined organs. We conclude that ultrasound diagnostics may be performed on this group of patients by interested general practitioners with special training. PMID- 2184542 TI - Continuous positive airway pressure breathing in supine and upright postures. AB - Continuous positive airway pressure (CPAP) breathing of 10 cmH2O was applied to 10 healthy conscious subjects both in supine and 70 degree head-up postures. CPAP increased the end-expiratory lung volume from 2.44 +/- 0.66 (S.D.) to 3.07 +/- 0.68 liters in supine subjects, and from 3.01 +/- 0.57 to 3.64 +/- 0.57 liters in head-up subjects. During CPAP, rib cage motion became predominant when compared to abdominal motion in upright posture. Among the respiratory parameters, inspiratory duration was significantly shortened during CPAP in either posture, but was changed less significantly by individual posture change alone. Mean inspiratory flow decreased during CPAP only in upright posture. Abdominal muscles were recruited for expiration during CPAP in either posture, and the EMG recorded from the lower intercostal space developed inspiratory activity during CPAP in head-up posture. All of 10 subjects felt most dyspneic during CPAP with the head up. We conclude that the mechanism of increase in lung volume during CPAP is mediated by different pathway from that of posture change, and that CPAP in upright posture can alter the respiratory pattern of the subject. PMID- 2184543 TI - Dose concepts for inhaled vapors and gases. AB - "Dose" for any toxicant is a shifting concept; thus, there is a frequent need for modifiers such as "administered" or "effective," when referring to dose. When applied to inhaled gases and vapors, "dose" is even more vague. The wide range of physicochemical properties associated with gases and vapors, the different target tissues that may be affected, and the variety of mechanisms involved in producing toxic effects combine to make a useful dose descriptor for one gas inadequate for another. Although models have been developed to describe dose for inhaled gases and vapors having a broad range of properties, it is often not clear which models are appropriate for which inhalant. In an attempt to resolve this dilemma, a classification scheme for inhaled gases and vapors, based on physicochemical properties, is offered in this report. In addition, various concepts of dose for inhaled gases and vapors are discussed with reference to the classification scheme. Finally, avenues for further research in the area of gas and vapor dosimetry are suggested. PMID- 2184544 TI - Synergistic interaction of a protease and protease inhibitors from Russell's viper (Vipera russelli) venom. AB - An acidic proteolytic enzyme, RVVX, was purified from Vipera russelli venom by successive chromatography on CM-Sephadex C-25, DEAE-cellulose and Sephadex G-100 columns. RVVX is a glycoprotein with a mol. wt of 79,000. It exhibited caseinolytic and factor X activating properties. Two trypsin inhibitors, TI-I and TI-II, were purified from V. russelli venom in a single step by CM-Sephadex C-25 column chromatography. The trypsin inhibitors interacted with the proteolytic enzyme RVVX. TI-I inhibited only the factor X activating property of RVVX while TI-II inhibited both, the caseinolytic and also factor X activating properties of RVVX. The edema inducing activity of RVVX increased markedly in the presence of non-edema inducing doses of TI-I and TI-II. RVVX, TI-I and TI-II were non-lethal in mice. The combination of RVVX and TI-II demonstrated enhanced toxicity. PMID- 2184545 TI - Cellular, biochemical and functional effects of ozone: new research and perspectives on ozone health effects. AB - Ozone, a toxic component of photochemical oxidant air pollution, has been the focus of considerable research efforts for several decades. In spite of this large body of work, questions remain as to the potential risks to human health represented by chronic low-level exposure to ozone. Newer studies in animals have provided fundamental information on the range of biochemical, functional and morphologic responses to ozone exposure. While the response to ozone exposure is extremely complex, some generalities have emerged which may aid attempts to apply the results of these studies to decisions regarding the protection of human health. PMID- 2184546 TI - Ascorbic acid safety: analysis of factors affecting iron absorption. AB - The potential for excessive iron absorption by subjects ingesting ascorbic acid doses above the recommended dietary allowance (60 mg) was evaluated by examining published literature (24 studies, 1412 subjects) in which ascorbic acid was part of a test meal given to determine effects on iron absorption. Three parameters associated with iron absorption were identified: (1) a relatively shallow slope for the dose-response curve relating ascorbic acid dosage (1-1000 mg) and percent iron absorption; (2) no significant effect of ascorbic acid on the absorption of high (60 mg) iron doses; and (3) an inverse relationship between iron absorption and plasma transferrin saturation. Ascorbic acid did not increase the incidence of 'high' iron absorbers (greater than 2 SD from population mean) above control levels; limited data for ascorbic acid doses greater than 100 mg/d indicated no change in the distribution of iron absorption values. PMID- 2184547 TI - 5-Fluorouracil carcinogenesis in BALB/c mice. AB - 5-Fluorouracil, a drug mainly used in the treatment of gastrointestinal tract neoplasms, was administered i.p. to BALB/c mice at the dose of 30 mg/kg body weight once a week for 50 weeks to test its carcinogenicity. The treatment induced a significant increase in lung tumor in both sexes (males, p less than 0.05; females, p less than 0.01) and tumors of the lymphoreticular system in female mice (p less than 0.001). These results suggest that 5-fluorouracil is carcinogenic in mice. PMID- 2184548 TI - Mitoxantrone (M) and vinblastine (V) in the treatment of advanced breast cancer. AB - Twenty-four patients with metastatic breast cancer, all but 1 pretreated with one or more chemotherapeutic regimens, were entered in a pilot study to assess toxicity and efficacy of the combination mitoxantrone and vinblastine. Dominant sites of metastases were viscera in 9 patients, bone in 10 and soft tissues in 5. All patients received mitoxantrone 10 mg/m2 i.v. on day 1 and vinblastine 1.7 mg/m2 by 4 hour infusion on days 3, 4 and 5, every 3-4 weeks. Objective responses (1 CR, 7 PR) were observed in 8 (38%) of the 21 evaluable patients. Median duration of response was 10.5 months. Of 12 patients pretreated with an anthracycline containing regimen, 4 responded (1 CR and 3 PR). Major toxicity was myelosuppression, grade 4 in 2 cases and grade 3 in 2 others. No evident alopecia was observed and only 1 case of grade 1 cardiac toxicity. In conclusion, mitoxantrone followed by vinblastine is an effective regimen in metastatic breast cancer also in pretreated patients, and previous anthracycline administration does not seem to reduce the percentage of response. Moreover, toxicity is generally mild. PMID- 2184549 TI - Evaluating radiation in combination with hyperthermia trials: the importance of clinical and technical parameters. AB - A proper evaluation of hyperthermia and irradiation trials is necessary to correctly interpret clinical results and to define limitations and properties of this new therapeutic approach. A better understanding of the "weight" of different technologic and clinical parameters that influence clinical response is thus clearly needed, particularly if future advances in hyperthermia technology and clinical results are to be expected. Patient variables, tumor variables, and treatment characteristics have been analyzed, and the difficulties of properly evaluating the "weight" of single parameters have been stressed. At the current state of knowledge, the Karnofsky index, site of disease (for regional heating), tumor status (recurrent versus metastatic disease) and XRT dose per fraction (for melanomas) seem to correlate with response. Tumor dimension, XRT total dose and thermal parameters reflecting the lowest tumor temperatures appear to statistically influence complete response rates of heated and irradiated tumors. In addition, a critical method of presenting results should be followed to enable comparison of data from different trials. PMID- 2184550 TI - Follicular non Hodgkin's lymphoma in adenolymphoma: report of a case. AB - A case of centroblastic centrocytic follicular lymphoma arising within a bilateral adenolymphoma of the parotid glands with involvement of the adjacent lymph nodes is reported. The patient was treated with combination chemotherapy and three years after the first cycle of therapy there was no evidence of disease. The occurrence of primary malignant lymphomas in the lymphoid stroma of an adenolymphoma has seldom been discussed in literature. All cases reported of follicular centre cell type were characterized by an indolent clinical course. PMID- 2184551 TI - [Streptococcal rheumatism in children and adults: a comparative study]. PMID- 2184552 TI - [Incidence of iron deficiency anemia in celiac disease: apropos of 26 cases]. PMID- 2184553 TI - [Livedoid paralytic syndrome secondary to intramuscular injection of benzathine penicillin]. PMID- 2184554 TI - [Immunology of Behcet's disease]. PMID- 2184555 TI - [Human toxoplasmosis]. AB - Toxoplasmosis infection is transmitted from cat faeces or insufficiently heated meat from e.g. pigs, sheep and goats. If pregnant women are infected with Toxoplasma gondii, there is a risk of infection of the foetus with the possibility of development of congenital toxoplasmosis and, in patients with AIDS, a latent infection may be activated with subsequent fatal encephalitis. Human infections with T. gondii are common but are frequently asymptomatic. The prevalence of T. gondii infection in the Danish population is not known exactly but preliminary investigations among pregnant women have revealed a prevalence of approximately 33% and the annual incidence is calculated to 0.5%. Legal abortion should be offered to pregnant women in whom toxoplasmosis is diagnosed on account of the risk of foetal damage. If legal abortion is not accepted or is not possible, treatment with spiramycin should be instituted. In immunosuppressed individuals with evidence of activation of latent T. gondii infection and children with congenital toxoplasmosis, treatment with combined pyrimethamine and sulphadiazine should be administered. Information about the routes of infection is important, particularly for sero-negative pregnant women as the routes of infection are limited so that it is reasonably easy to avoid infection. PMID- 2184556 TI - [A comparative study of atenolol (Tenormin) and the combined preparation atenolol/chlorthalidone (Tenoretic Mite) in essential hypertension. A randomized double-blind study from general practice]. AB - Two hundred and ninety-two hypertensive patients from general practice who had previously been treated with a diuretic with insufficient effect participated in a randomised trial for a period of three months. A total of 115 patients completed treatment with 50 mg atenolol (Tanormin) and 121 were treated with the combined preparation consisting of 50 mg atenolol and 12.5 mg chlothalidone (Tenoretic Mite) while 56 patients defected from the trial. In both of the groups, the average blood pressure was reduced significantly already after treatment for one month. A significantly greater number of patients receiving combined treatment achieved satisfactory diastolic blood pressures (less than 90 mmHg), the proportions being 78% and 54%, respectively. Better effects from combined treatment were found particularly in patients over 60 years of age and in females. No significant differences were observed between the side-effects of the regimes nor in the laboratory values registered during treatment. PMID- 2184557 TI - [Insuject-X for children. A clinical trial of the NPH insulin pen]. AB - The use of Insuject-X for NPH insulin was tested by 21 children, age less than or equal to 10 years with insulin dependent diabetes mellitus less than or equal to 1 year, on conventional treatment with NPH insulin once or twice daily. After a preliminary period of one month the syringe injection regimen was changed to injections by Insuject-X for a four-month "pen" period. We observed no significant changes in metabolic control. The mean potency of NPH insulin in partly used cartridges was 103.6 +/- 5.6 IU/ml (range 91.0-118.1, n = 39) with no correlation to the residual volume or days of use. Measurements over 110 IU/ml were seen at the end of the study indicating the need of repeated instruction in use of the pen by children. No microbial contamination of the cartridges, nor any local reactions at injection sites were found. We observed more technical problems than in adult studies indicating that children handle the pen more roughly. The accept of Insuject-X was good as a more convenient means of injecting. All of the children preferred to continue using it. PMID- 2184558 TI - [Anesthesiologic aspects of narco-curare-electroshock treatment]. AB - The physiology and side-effects of narco-curare-electric shock treatment are reviewed on the basis of the literature and, similarly, risk groups are delimited. Directives for preoperative assessment, the anaesthesiological procedure and per- and postoperative observation are given. It is concluded that the NCE procedure is associated with a low risk and slight mortality provided the above-mentioned conditions are observed. Patients with cardiovascular disease constitute the greatest risk group and should receive optimal medical treatment prior to NCE. In cases with raised intracranial pressure, NCE should only be employed with great reservation. ECG monitoring, treatment with atropine and preliminary treatment with oxygen are advised in general. Withdrawal of psychocopharmaca prior to NCE is rarely indicated. PMID- 2184559 TI - [Medical informatics]. AB - Medical informatics is the discipline concerned with information and information streams in health care. The development of information technology has been intensified in recent years and is now influencing the international development within the health care sectors. During the coming decade, integrated hospital networks will supple communication within and between hospitals. New productivity measures useful in administrative planning are being developed. Patient data are being digitalized and stored electronically, and interactive media are implemented in education. Primarily, however, chip-based technologies find application in the evaluation of the increasing quantity of paraclinical data. Internationally product development and research are actively underway. The EEC has established development programmes specifically stimulating these activities. Is Denmark going to take an active part in this development, formalized frames are required. PMID- 2184560 TI - [Cervix factors as a cause of infertility]. AB - The uterine cervix plays an important role in the natural fertilization process and, consequently, it is also a significant factor in infertility. In about 6% of infertile couples, the infertility is caused by the cervical factor. The post coital test (PCT) is the most essential diagnostic procedure. A good PCT result excludes the cervical factor as the cause of infertility. A poor or negative PCT result, on the other hand, only indicates that the cervical tract is the cause in the case of women with verified ovulation and in whom other causes have been excluded. Treatment of the cervical factor has always been difficult. Intrauterine insemination is the best documented treatment method with a pregnancy rate of about 30%. In future, gamete intrafallopian transfer (GIFT) and in vitro fertilization (IVF) may be alternatives in the treatment of infertility owing to the cervical factor. PMID- 2184561 TI - [The use of urapidil in anaesthesia. A selective S1A-serotonin receptor antagonist with antihypertensive action]. AB - Serotonin is a vasoactive amine which is considered to play a pathogenetic role in systemic hypertension on account of the peripharal vasotonic effect of serotonin. The central serotoninergic neurones excitatory influence of the sympathetic tone may, however, be a contributory cause. Urapidil is a selective S1-serotonic receptor-agonist with alpha-blocking effect. This is considered to influence the presynaptic receptors of the serotoninergic neurones and thus to inhibit the excitatory influence on the sympathetic system. It reduces the blood pressure by reducing the peripheral vascular resistance without simultaneous provocation of reflex tachycardia or reduction in the minute volume of the heart. In anaesthesiology, this may be employed for perioperative hypertension. The preparation appears to be particularly useful in neuroanaesthesia as in contrast to other antihypertensive agents, it does not appear to alter the intracranial pressure. PMID- 2184562 TI - [Do pregnant women with a low-situated placenta in the 16th week constitute a risk group?]. AB - The object of this investigation was to elucidate whether pregnant women with low placed placentae in the 16th week of pregnancy had more frequent haemorrhagic complications during pregnancy or during delivery and to demonstrate how many had placenta praevia at the time of delivery. In addition, the frequency of Caesarean section, the perinatal mortality, birthweights under 2,500 g in the infants delivered and placental anomalies were registered. A total of 1,572 pregnancies were investigated sonographically at about the 16th week of pregnancy and in 166 (10.6%) the placenta was found in the lower uterine segment. 40% of the 15 women with complete placenta praevia at the 16th week of pregnancy developed haemorrhage necessitating hospitalization, 27% were delivered by Caesarean section and 20% had placenta praevia at delivery. Out of 99 women with partial placenta praevia at the 16th week of pregnancy, one was found to have placenta praevia at the time of delivery but no significantly increased risk of haemorrhage necessitating hospitalization, abortion or Caesarean section. In 52 women with "deep insertion" of the placenta at the 16th week of pregnancy, one was subsequently found to have complete placenta praevia but the frequency of complications was not increased as compared with that in women with a free orifice. This investigation reveals a basis for control sonography of women with complete placenta praevia at the 16th week of pregnancy. PMID- 2184563 TI - Medullary sponge kidney and staghorn calculi. AB - We describe a 65-year-old female with bilateral staghorn calculi who presented with a Proteus mirabilis perinephric abscess secondary to a ruptured lower pole hydrocalyx. Radiologic evidence was consistent with underlying medullary sponge kidney (MSK) disease. Despite expectations to the contrary, MSK, a disease notable for many risk factors capable of precipitating staghorn disease, is rarely associated with coexistent staghorn calculi. A discussion of the concurrent risk factors and a possible hypothesis regarding the lack of coexistence follows. PMID- 2184565 TI - A new digital phased array system for dynamic focusing and steering with reduced sampling rate. AB - In order to enhance the resolution of the ultrasonic B-mode image, digital techniques for dynamic focusing and steering have been receiving a great deal of attention for a long time. In this paper, we present the theory and preliminary experimental results for a new architecture of a fully digital B-mode imaging system with this desired feature. The system employs the Pipelined-Sampled-Delay Focusing (PSDF) scheme to eliminate the bulky memory addressing and interpolation circuits which are needed in conventional digital imaging systems. To reduce hardware requirements and the bandwidth required for digital processing, we describe an efficient method to generate the sampling clocks for dynamic focusing and steering and some modified bandwidth sampling techniques to reduce the sampling rate for signal digitization. Using these methods, it is possible to achieve dynamic focusing and steering in real-time sector imaging using a linear phased array. PMID- 2184564 TI - Adjuvant systemic chemotherapy after complete transurethral resection of superficially invasive bladder carcinoma (T1 G3-4 and T2 G2-4). AB - A prospective multicenter phase-two study was initiated in 1983 to evaluate the effect of systemic chemotherapy after complete resection of T1 G3-4 and T2 bladder carcinomas. Chemotherapy consisted of three cycles of cisplatin alone, a modified MVAC scheme or the combination of cisplatin and methotrexate. 52 patients entered the study. After a medium follow-up of 36 months 11 patients developed progression of the disease; cystectomy had been performed in 8 patients and 6 patients died due to progressive bladder carcinoma. These encouraging results should be the base for a randomized trial with the aim to improve survival and avoid cystectomy in selected patients with superficially invasive bladder cancer. PMID- 2184566 TI - Phase-derivative imaging. III: Theoretical derivation of first and second order statistics. AB - The echo signal obtained from a homogenous and isotropically scattering medium can be described as a Poisson time series which is convolved with the transmission pulse of the transducer. The probability density function (pdf) of this signal approximates to a Gaussian pdf for narrowband pulse waveform. Methods to derive the phase-derivative (PD) signal from the complex envelope and the preenvelope of the echo signal are described. The first order pdf of the PD asymptotically becomes a Gaussian pdf by smoothing. Since the rectified PD is employed to obtain 2-dimensional grey scale images, the first order pdf as well as the signal-to-noise ratio (SNR) of this signal are also derived. The rectified PD is further smoothed by a cosine time window prior to the imaging. The SNR and the autocorrelation function (in the axial direction) of this latter signal can be derived under the assumption of a Gaussian spectrum of the transmission pulse. These first and second order characteristics of the PD images are calculated for the conditions employed in simulations and experiments reported previously and are quantitatively compared to the values obtained from these. PMID- 2184567 TI - A transaxial compression technique (TACT) for localized pulse-echo estimation of sound speed in biological tissues. AB - We describe a new method for the estimation of the speed of sound in soft tissues in the pulse-echo mode. A transducer imparts an accurate transaxial compression to the tissue, and the corresponding change in the arrival time of an echo feature is measured. The ratio between the compressed depth and the difference in arrival time is taken as the estimate of the speed of sound. A second, noncompressing transducer is used to correct for distal tissue movement. We show theoretically and experimentally that accurate speed of sound estimations can be made in overlying and underlying tissue mimicking layers. PMID- 2184568 TI - Global breast attenuation:control group and benign breast diseases. AB - This paper deals with the estimation of the slope of attenuation in human breast tissue. The measurement is done in the reflection mode with a short time Fourier analysis. All important factors such as diffraction effect, tissue depth and specular reflectors are taken into account. A population of 49 normal women shows large inter-individual variations of the attenuation coefficient. A multiple linear regression allows correlation of this variation with the duration of the woman's genital life and pregnancies. A preliminary study is done on 10 benign diffuse breast diseases and shows a weak correlation with the type of the breast: normal or pathological. The utility of the quantification is discussed for one case of large fibrocystic disease. PMID- 2184569 TI - Backscatter coefficient measurements using a reference phantom to extract depth dependent instrumentation factors. AB - In previous work, we demonstrated that accurate backscatter coefficient measurements are obtained with a data reduction method that explicitly accounts for experimental factors involved in recording echo data. An alternative, relative processing method for determining the backscatter coefficient and the attenuation coefficient is presented here. This method involves comparison of echo data from a sample with data recorded from a reference phantom whose backscatter and attenuation coefficients are known. A time domain processing technique is used to extract depth and frequency dependent signal ratios for the sample and the reference phantom. The attenuation coefficient and backscatter coefficient of the sample are found from these ratios. The method is tested using tissue-mimicking phantoms with known scattering and attenuation properties. PMID- 2184570 TI - [Biological markers in renal cell carcinoma]. AB - The development of immunoassays for the diagnosis of renal cancer promises significant improvements in clinical treatment. Monoclonal antibodies have defined numerous kidney-associated antigens. In at least one instance (ADAbp), an immunoassay has already been established that is helpful in the diagnosis of benign renal diseases. A similar approach may also be useful in renal cancer. Similarly, in at least one instance a previously undefined peptide (HHM factor) has been cloned and sequenced. Synthesis of this peptide and the production of antibodies to it is imminent. The possibility of measuring this peptide and/or the many other aberrantly produced peptides associated with this cancer would presumably mean a substantial improvement in early diagnosis and therefore cure rates in renal cancer. The final role of chromosome changes in the diagnosis and determination of prognosis cannot yet be defined. PMID- 2184571 TI - [Tumor markers and prognostic parameters in urinary bladder cancer]. AB - Ideal tumor markers for use in the primary diagnosis or follow up of superficial or invasive cancers have not yet been found. Nonetheless, the literature contains references to parameters that are relevant to prognosis and to markers for bladder tumors, and many of these are certainly of value when specific questions are addressed. Urinalysis has been considerably refined and yields information on superficial tumors. Quantitative immunocytology is used to check whether prophylactic treatments are indicated and, if so, for how long; conventional cytology is helpful in the clinical follow up after BCG treatment of carcinoma in situ. In the present paper all important markers for urothelial cancer are reviewed and their value in diagnosis and treatment is discussed. PMID- 2184572 TI - [The value of corpus cavernosum sonography following administration of vasoactive substances in the diagnosis of patients with erectile impotence]. AB - In 70 Patients with erectile dysfunction, ultrasound examination of both corpora cavernosa after intracavernous injection of papaverine was done using B-scan, Duplex scan and Doppler color. B-scan can detect morphological disease in a penis profundis, the higher degrees of cavernous muscle myopathia, and disease of the tunica albuginea. For the analysis of pulse curve and the measurement of blood flow velocity, the Duplex scan is necessary. Doppler color imaging enables ultra sonographic examination of a dorsalis and a penis profundis and can detect intracavernous vascular pathology. The results show that ultrasonography is an important diagnostic tool in patients with erectile dysfunction. A differentiated therapeutic strategy can be based on this examination, especially when revascularization procedures are being discussed. Additionally, better follow-up of patients under self-injection therapy is possible. PMID- 2184573 TI - A capsid-associated protein of the multicapsid nuclear polyhedrosis virus of Orgyia pseudotsugata: genetic location, sequence, transcriptional mapping, and immunocytochemical characterization. AB - Two lambda gt11 clones containing overlapping DNA inserts encoding portions of a structural protein gene from Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus (OpMNPV) were identified by their immunoreactivity with polyclonal antisera produced against purified polyhedra-derived virus. Sequence analysis of a 3.6-kb region of the baculovirus genome (map units 69.1-71.6) from which the lambda gt11 inserts originated revealed an open reading frame of 1872 nt (624 amino acids) encoding a predicted protein of 70.6 kDa. Northern blot, primer extension, and 3' S1 analysis of this ORF indicated that an mRNA of approximately 2100 nt was transcribed from this gene. The mRNA appears to initiate from a late promoter/mRNA start site consensus sequence GTAAG and is expressed at late times postinfection. A gene fusion containing the C-terminal 368 amino acids of the gene was constructed using a bacterial trpE expression vector. Rabbit antiserum made against the purified fusion protein reacted with a protein of 87 kDa on Western blots of infected cell extracts at 24 hr p.i. and thereafter. The p87 protein was shown to be a component of both budded and polyhedra-derived virus and purified capsids. Immunofluorescence analysis indicated that p87 is expressed late in infection and concentrated in infected cell nuclei. PMID- 2184574 TI - Functional substitution of the basic domain of the HIV-1 trans-activator, Tat, with the basic domain of the functionally heterologous Rev. AB - The tat gene of HIV is a strong activator of the viral LTR. The Tat protein contains a highly basic domain that is important for its transport to the nuclear/nucleolar locations. The Tat basic domain when fused to Escherichia coli beta-galactosidase directed the chimeric protein to the nucleus and nucleolus. Tat mutants lacking the entire basic domain were severely defective in trans activation. Substitution of the basic domain of Tat with that of the functionally unrelated HIV-1 Rev protein targeted the chimeric protein to the nucleolus and restored the function of Tat. In contrast, substitution with the nuclear targeting signal (NLS) of SV40 T antigen targeted the chimeric protein to the nucleus and accumulation in the nucleolar region was excluded. The Tat-NLS chimeric protein did not restore the trans-activation function of Tat efficiently. These results indicate that the arginine-rich basic domain of the trans-activator, Tat, and post-transcriptional trans-regulator, Rev, are functionally similar with regard to trans-activation of HIV-1 LTR. PMID- 2184575 TI - Interaction of a noncytopathic human immunodeficiency virus type 1 (HIV-1) with target cells: efficient virus entry followed by delayed expression of its RNA and protein. AB - Recently described noncytopathic human immunodeficiency viruses type-1 (HIV-1) form a new category within the HIV-1 family due to their unique biological properties and predominant occurrence in symptom-free individuals. To study the mechanism of noncytopathic HIV-1 infection, we compared the infectivity and life cycles of two closely related HIV-1 clones with noncytopathic (N1T-E) or cytopathic (N1T-A) properties. N1T-E virus exhibited slow kinetics of infection in T cells and monocytes. Slow infection was not due to defective virus entry, because N1T-E and N1T-A exhibited equally efficient virus-cell fusion activity and nucleocapsid internalization. Kinetic studies of N1T-E genome expression revealed low levels of viral RNA, structural proteins, and Tat protein during the first 7 days after virus entry. In contrast, cells infected with the same dose of cytopathic N1T-A virus began to express high levels of genomic RNA, structural proteins, and Tat protein within 48 hr of infection; the expression peaked on Day 5, followed by complete cell lysis. No delay in N1T-E replication, as compared to N1T-A, was observed after transfection of cloned N1T-E proviral DNA. N1T-E virus had intact Tat, Rev, and fusion functions and replicated well in chronically infected cells. These results suggest that delayed processing or expression of HIV-1 genome during the early phase of the virus replicative cycle is an important determinant in noncytopathic infection. PMID- 2184576 TI - Deduced sequence of the bovine coronavirus spike protein and identification of the internal proteolytic cleavage site. AB - The sequence of the spike (also called peplomer or E2) protein gene of the Mebus strain of bovine coronavirus (BCV) was obtained from cDNA clones of genomic RNA. The gene sequence predicts a 150,825 mol wt apoprotein of 1363 amino acids having an N-terminal hydrophobic signal sequence of 17 amino acids, 19 potential N linked glycosylation sites, a hydrophobic anchor sequence of approximately 17 amino acids near the C terminus, and a hydrophilic cysteine-rich C terminus of 35 amino acids. An internal Lys-Arg-Arg-Ser-Arg-Arg sequence predicts a protease cleavage site between amino acids 768 and 769 that would separate the S apoprotein into S1 and S2 segments of 85690 and 65153 mol wt, respectively. Amino terminal amino acid sequencing of the virion-derived gp 100 spike subunit confirmed the location of the predicted cleavage site, and established that gp 120 and gp 100 are the glycosylated virion forms of the S1 and S2 subunits, respectively. Sequence comparisons between BCV and the antigenically related mouse hepatitis coronavirus revealed more sequence divergence in the putative knob region of the spike protein (S1) than in the stem region (S2). PMID- 2184577 TI - Recommendations of the Coronavirus Study Group for the nomenclature of the structural proteins, mRNAs, and genes of coronaviruses. PMID- 2184578 TI - [Function of the pineal body in cancer and aging]. PMID- 2184580 TI - [Statistical methods in the study of carcinogenicity in animal experiments]. PMID- 2184579 TI - [Antiblastic effects of polycation polyhexamethyleneguanidine, a representative of a new class of antitumor drugs]. PMID- 2184581 TI - [Principles of improvement in the early diagnosis of malignant neoformations]. AB - Early diagnosis of the most frequently--occurring cancers cannot be improved unless integrated approach to the problem is used. This should include application on a wider scale of regular medical check-ups in population older than 40 years with more extensive but justified use of modern laboratory and instrumental methods and computer--based follow-up programs. PMID- 2184582 TI - [Transrectal and transvaginal echography in cancer of the rectum]. AB - To assess the diagnostic value of ultrasonography in rectal carcinoma, the procedure was performed in 48 such cases. Stage was reliably established in the majority (95.8%) of patients. False--negative conclusion on the muscular layer integrity was made in one case and inflammatory infiltrate was misdiagnosed as cancer in another. Pararectal lymph nodes were visualized in 62% of patients whereas regional ones--in 5 (10.4%); their metastatic origin was confirmed with fine--needle aspiration biopsy and lymphography. Ultrasonic scintigraphy identified nodular lesions in the liver parenchyma in 10 cases; the malignant nature of those foci was verified in 90% by histo- and cytologic examination of samples obtained by fine--needle aspiration biopsy. PMID- 2184583 TI - [The epidemiology of escherichiosis at recreation areas]. AB - A study of epidemiological and microbiological data (2073 epidemiological examinations of patients with escherichiosis and carriers of pathogenic Escherichia and microbiological examination of 2156 strains of pathogenic Escherichia) in two recreation zones with different types of industry (clean recreation zone and that with developed industry) revealed differences in the incidence of the escherichiosis morbidity and carrier state of Escherichia, age structure of patients and carriers, seasonal distribution of the patients and proportion of the serogroups of pathogenic Escherichia isolated in the zones. It is concluded that above findings are of importance for planning antiepidemic measures in case of escherichiosis. PMID- 2184584 TI - [Characteristics of blood microcirculatory disorders during the formation of chronic cor pulmonale (a review of the literature)]. PMID- 2184585 TI - [Liver involvement in chronic alcoholic intoxication (a review of the literature)]. PMID- 2184586 TI - [Diagnosis of the involvement of the subdiaphragmatic lymph nodes and organs in lymphogranulomatosis (a review of the literature)]. PMID- 2184587 TI - [Somatic disorders in drug addiction (a review of the literature)]. PMID- 2184588 TI - [Acceptance crisis in science? On the future of research]. PMID- 2184589 TI - [History of the institute of general and experimental pathology and the propedeutic clinic of the German University in Prague]. AB - The department of general and experimental pathology at the German University of Prague was founded in 1872. From the very beginning the "Propaedeutic Clinic" was attached to the department, with the initial function of providing the necessary demonstration material for the lectures. The department had altogether four directors between 1872 and 1945 (the propaedeutic clinic was dissolved in 1935 already): Philipp Knoll (1841-1900), Heinrich Ewald Hering (1866-1948), Artur Biedl (1869-1933) and Julius Rihl (1879-1961). Important fundamental research was carried out both at the department and at the clinic and certain pupils who trained at these twin institutions became famous subsequently and some even founded their own schools. Amongst these distinguished scientists were Wilhelm Raab (1895-1970), Hans Selye (1907-1982) and Maximilian Reiss (*1900). Important research work on the physiological functions of and pathological changes in the circulatory system and metabolic pathways was undertaken at both Prague institutions. These publications made a significant contribution to the theoretical basis for the practice of medicine. PMID- 2184590 TI - A new cold storage solution for kidney preservation. Comparing UW and Eurocollins solution. PMID- 2184591 TI - [Forms of hormonal contraception]. PMID- 2184592 TI - [The significance of post-coital hormonal contraception for prevention of conception]. PMID- 2184593 TI - [Hormonal contraception in adolescents and in pre-menopause]. PMID- 2184594 TI - [Favorable effects and unwanted side effects of hormonal contraceptives]. PMID- 2184595 TI - [Development of contraception with steroids]. PMID- 2184596 TI - [Changes in carbohydrate and lipid metabolism and modification of diabetes mellitus by hormonal contraceptives]. PMID- 2184597 TI - [Lipid metabolism and hormonal contraceptives]. PMID- 2184599 TI - [Cardiovascular diseases with oral contraceptives: risks and benefits]. PMID- 2184598 TI - [Blood pressure behavior in contraception with hormonal contraceptives]. PMID- 2184600 TI - [Effect of hormonal contraceptives on the voice]. PMID- 2184601 TI - [Changes in the immune system caused by hormonal contraception]. PMID- 2184603 TI - [Hormonal contraception and the risk of cancer]. PMID- 2184602 TI - [Hormonal contraception and pregnancy]. PMID- 2184604 TI - [Carl Westphal--his life and work]. PMID- 2184605 TI - [The 125th birthday of the founder of phoniatry--Hermann Gutzmann]. PMID- 2184606 TI - [Characteristics of estrogens and gestagens]. PMID- 2184607 TI - [Definition and clinical significance of oscillation parameters (fixed frequency technic)]. AB - Starting from the polyvalent sense of a limitation of the maximum available respiratory flow there is to be pointed to the necessity of the decentralized measurement of resistance. The instrument IfM E1 permits the use of the simple forced oscillation technique for estimations of ROS and the derived values delta ROS and STAV all over the country. The advanced forced oscillation method, based on the fixed frequency technique, contained the option for estimation of the residual volume and especially the phase-angle. The knowledge of psi, Re and phi can make the oscillatory testing of airways resistance more surely. Taking into consideration the dependence of the phase signal on lung volume can state noninvasive different facts about the compliance of the lung-thoracic-diaphragm system. PMID- 2184608 TI - [Methodology and assessment of testing bronchial reactivity]. AB - Starting from diagnostic relevance of non specific bronchial challenges the principles and experiences of a screening type acetylcholine test which is recommended as a standard in GDR since 1974 are discussed. For special tasks like longitudinal studies and clinical pharmacology a threshold method using histamine was derived and modified from literature. Special attention is paid to diagnostic, prognostic and expertizing relevance of non specific bronchial hyperreactivity. PMID- 2184609 TI - [Methodology and assessment of diagnosis of the hemodynamics of pulmonary circulation]. AB - As to the examination of pulmonary haemodynamics the microheartcatheterization for sounding the right ventricle and the pulmonary artery should be found more acceptance in numerous pulmological and cardiological laboratories for verifying pulmonary hypertension, in preliminary examinations for vitium cordis, in intensive medical care for the continuous registration of haemodynamic parameters or to obtain expert opinion in connection with an occupational disease. Feasible measuring technique and method are put forward for making comparable evaluations. Reference values of haemodynamic parameters at rest and during bicycle exercise in sitting and lying position and regressions calculated on oxygen consumption and on age dependence are set forth. Critical suggestions on obtaining variables are given. PMID- 2184610 TI - [Diagnosis of lung function in bronchial asthma]. AB - Chronic obstructive airway diseases have only slight demand on lung function diagnostics according to the number of methods and technical level. But we have the demand of a high rate of lung function, more than in all other lung diseases. The expiratory peak flow (PEF) seems to be a suitable parameter for daily control. PMID- 2184611 TI - [Electronic spirometry]. AB - Electronic spirometry on the basis of forced expiration and flow-volume-curve possess many advantages for the detection of ventilatory alterations in human lung. PMID- 2184612 TI - [Peak flow measurement]. AB - Peak flow rate measurements with a simple device are useful in detecting and objective assessment of obstructive airway disease. They are easy to perform and offer a rational basis for antiobstructive treatment. PMID- 2184613 TI - [Blood glucose self-monitoring with the Glucosignal test strip in routine practice--experiences of a district diabetes center]. AB - 32 patients (19 females, 13 males; 28 type I diabetics and 4 type II diabetics) with a diabetes mellitus we taught the blood glucose self-control under working conditions by means of the test strip Glucosignal. 9 diabetics were excluded from the investigation. The main reasons for this were: inability to acquire the withdrawal technique, abuse of alcohol, unreliability and attitude of opposition to the own disease. During the duration of observation of on an average 13.8 months (11 to 25 months) in the remaining 23 patients an improvement of metabolism could be obtained with the same need of insulin. In three quarters of the cases correction of the metabolism were made by the patients by insulin variation and only for the smallest part by physical conditioning. Intensive theoretical and practical training and good motivation of the patients decide on success or failure of the optimization of metabolism. The various possibilities of an influence on ambulatory day-night-profiles under working conditions are discussed. PMID- 2184614 TI - [Halle physicians as historical witnesses and specialty chronologists. IV. From the memoir literature of the era before the March Revolution]. AB - On the epoch before the March revolution 1848 several reports of witnesses of time written by Halle physicians are existing. By a book publication of the year 1847 the physician Julius Rosenbaum informed the publicity about details of internal facts of the faculty. The future physician Ludwig Paetsch who entered the university in the same year later on wrote his reminiscences of his years as a student in Halle. The conditions in the town on river Saale and the university are plastically described in the two papers. PMID- 2184615 TI - [Relationship between disregulations in the hemostasis system and thrombogenesis]. PMID- 2184616 TI - [Physiological influences on the enzyme elimination with urine]. AB - It is desirable to know the factors determining the large interindividual and interindividual variation of urinary enzyme excretion rates among normal individuals to allow a better understanding of pathological states. The following factors seems to play a significant role in influencing total enzyme efflux rates: urinary flow, age, sex, biorhythms, genetic factors, hormonal situation (including pregnancy), nutrition, and physical activity. PMID- 2184617 TI - [The determination of cortisol in plasma with a direct luminescence enzyme immunoassay]. AB - The assay is based on the luminescent measurement of horseradish peroxidase. The IgG fraction of a cortisol antiserum is coated on suitable polystyrene tubes (in use for the measurement of luminescence). The enzyme activity of bound label was determined using a p-iodophenol enhanced chemiluminescent reaction. The assay was sensitive and precise for a wide cortisol concentration range and showed a good agreement with conventional ELISA-technique. There was no extraction necessary for cortisol from plasma. The diluted sample was heated to 60 degrees C or 8 aniline-1-naphthalene sulfonic acid was added in order to release cortisol from protein binding in plasma. PMID- 2184618 TI - [The role of the liver in body stress reactions]. PMID- 2184619 TI - [Epidermal growth factor (EGF)]. PMID- 2184620 TI - [The humoral regulation of intestinal enzyme activity]. PMID- 2184621 TI - [The neurophysiological mechanisms of the oculomotor behavior of mammals]. PMID- 2184622 TI - [Emotional tension, the postural regulation of blood circulation and some contradictions in the concepts of the pathogenesis of arterial hypertension]. PMID- 2184623 TI - [Human EEG reactions to discontinuous light exposures of different frequencies]. PMID- 2184624 TI - [The Central Museum of History of Medicine]. PMID- 2184625 TI - [4-way immunosuppression in pre-sensitized recipients of allogenic cadaver kidney transplants]. AB - As a result of introduction of quadruple immunosuppression using cyclosporine, antithymocyte globulin, azathioprine and prednisone in immunological high-risk patients with a presensitization greater than or equal to 80% and/or multiple grafts the rate of immediate graft function could significantly increased, the frequency of rejection and graft rupture was reduced and the patient survival rate could improved to 100%. The problem of vascular rejection should resolved by a more aggressive biopsy approach. PMID- 2184626 TI - [The significance of experimental kidney transplantation for clinical practice]. AB - After presentation of the history of kidney transplantation and experimental transplantation research with own contributions like microsurgery and photochemotherapy the importance of experimental kidney transplantation as the basis of progress in clinical transplantation is represented. PMID- 2184627 TI - [Agenesis of the inferior vena cava]. AB - It is reported on an asymptomatic rare vascular anomaly, the agenesis of the inferior vena cava. The knowledge of such malformations is important in operative procedures. PMID- 2184628 TI - [Analysis of risk in the perioperative period]. AB - Operative risks should be assessed before surgical intervention not only by heuristic means, but in addition also by quantitative methods. ASA-classification and Recovery Index (McPeek) are offered for a critical routine assessment of global perioperative risk. PMID- 2184629 TI - [Diagnostic and therapeutic procedures in liver injuries in children]. AB - Despite of severity of posttraumatic liver lesions after blunt abdominal trauma the availability of modern imaging diagnostic methods has changed the therapeutic concept. Nonoperative treatment attained an alternative place to operative procedures. For this kind of treatment personal and technical premises are mandatory. With ultrasound and computed tomography are non-invasive methods for diagnosis available. Paracentesis has lost of importance. This report of 7 children with liver laceration within 6 years discuss diagnostic and therapeutic practice. Decision for operative or nonoperative treatment depends on critical evaluation. PMID- 2184630 TI - [Animal experiment study of performance ultrasound in the welding of liver wounds]. AB - Liver cuts were performed on 21 Mini-Leewe-pigs and than closed with suture and by ultrasonic welding with Ligament-FIMOMED and Gelaspon. The sound pressure leads to the forced penetration of the monomere into performed gaps. The application of the ultrasound is sensible in order to force the polymerisation. The experiments resulted in the succesful closure of the liver wounds in all cases where ultrasonic welding of Fimomed-Gelaspon compound was used. Application to human medicine is, however, not yet justified. PMID- 2184631 TI - [Our surgical heritage. On surgical education at the former Dresden Collegium medico-chirurgicum]. PMID- 2184632 TI - [Modifications to the surface of T-lymphocytes in chronic candidiasis of the skin and mucous membranes]. AB - 27 patients with chronic candidiasis of the skin and mucous membranes have been examined with a view to study the expression of E-receptors and its changes after the incubation of T-lymphocytes with theophylline, levamisole, thymaline and Candida albicans antigen. This study has revealed that, in comparison with healthy persons, most patients show decreased expression of E-receptors, and the character of their changes after incubation with the above-mentioned preparations is essentially different. The deviations revealed in this study have been regarded as the modification of T-cell membranes, which is seemingly one of the reasons of the weak competence of T-cells. In its turn, the expression of E receptors may be considered as an indicator of the influence of different factors on T-lymphocytes. Substances altering the level of cyclic nucleotides in the cell, the antigenic fractions of the fungal causative agent, the suppression or blocking the action of thymic hormone-like substances may serve as such factors. PMID- 2184633 TI - [A comprehensive system for the nonspecific prevention of influenza and acute respiratory diseases: the potentials and outlook]. PMID- 2184634 TI - Incidence of lesions of the saphenous nerve after partial or complete stripping of the long saphenous vein. AB - To find out whether the usual total stripping of the long saphenous vein in operations for varicose veins could be replaced by a less traumatic removal of only the femoral part of the vein, a randomised prospective study was carried out in 163 consecutive patients, of whom 157 were evaluable. Group A (n = 80) had total stripping and group B (n = 77) had partial stripping (extraction of the long saphenous vein from the groin to immediately below the knee). The two groups, which were comparable, were assessed three months after operation when 75 in group A (94%) and 75 in group B (97%) had excellent or good relief of symptoms and comparable absence of residual varicosities. Lesions of the saphenous nerve were found in 31 in group A (39%) and 5 in group B (7%) (p less than 0.001). There were few other complications. We conclude that preservation of the distal long saphenous vein not only reduces nerve damage, but also retains enough vein for use should coronary artery bypass or peripheral vascular grafting be necessary in future. PMID- 2184635 TI - Advantages and disadvantages of mechanical vs. manual anastomosis in colorectal surgery. A prospective study. AB - The merits of mechanical versus manual anastomosis were evaluated in a prospective study of 48 patients undergoing resection of colonic or rectal cancer. The analyzed factors included the time required for construction of the anastomosis, the length of hospital stay, the cost/benefit ratio and complications. The anastomosis was manually performed with monolayer polyglactin 910 sutures in 24 cases and mechanically with an E.E.A. stapler in 24. The anastomosis time averaged 14 min in the suture group and 14.3 min in the stapling group, and the respective hospitalization times were 16 and 17 days. The mean cost was 48,000 lire in the manual, and 200,000 lire in the mechanical group. Four complications occurred in each group. Apart from the cost, no intergroup difference was statistically significant. PMID- 2184636 TI - Sphincter of Oddi motility. AB - After a short introduction (chapter 1), anatomy is described in chapter 2. The sphincter of Oddi (SO) can be divided into the choledochal, pancreatic and ampullar sphincter in addition to the intermediate fibres. In anatomic studies the pancreatic and ampullar sphincters are described in only one third and sixth respectively. This is in disaccordance with manometric studies where SO activity always is registered in the pancreatic sphincter after total biliary sphincterotomy. Chapter 3 discusses whether or not the SO is a true sphincter. Activity simultaneous with the duodenum occurs in the interdigestive phase III, but more often duodenal and SO activity is dissociated. It is concluded that the vast evidence supports the SO as a true sphincter. Chapter 4 concerns methods for investigation of the SO activity. The manometric methods are divided into direct and indirect studies, and advantages and disadvantages are discussed. The direct manometric method employing a perfusion system is highlighted, and interpretation of tracings and artifacts described. In chapter 5 physiological aspects are considered. Slow waves are present in the SO, and the activity related to the migrating motor complexes of the duodenum. Apart from interdigestive variation the food stimulated pattern is mentioned. Nervous and hormonal control as well as the relation to other parts within and outside the pancreatico-biliary system is outlined. The SO receives nervous fibres from both the sympathetic and the parasympathetic system. The alfa- and cholinergic neurons stimulate whereas the beta-neuron inhibits the SO. Furthermore inhibitory non-adrenergic, non cholinergic neurons are present. Cholecystokinines inhibitory action on the SO are brought about via a stimulation of inhibitory neurones since the peptide has a direct stimulatory action on the SO muscle. The most important reflex regulation of the SO is elicited by gallbladder pressure increase with inhibition of the SO. Probably a similar reflex relationship exists between the common bile duct and the SO. The SO is considered important in the regulation of biliary flow, and probably also pancreatic flow, although the latter is only poorly studied. Furthermore the SO is believed to play a role in the prevention of reflux from the duodenum. In chapter 6 studies in normals, controls and patients with diseases in the biliary and pancreatic system are surveyed. In patients with gallbladder stones no changes in SO activity has been disclosed. In patients with common bile duct stones some have found increased antiperistalsis, others not.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2184638 TI - The neuroleptic malignant syndrome and its differentiation from lethal catatonia. AB - Neuroleptic malignant syndrome and lethal catatonia are potentially life threatening diseases with similar clinical features, including fever, akinesia and rigidity. Differential diagnosis is difficult but possible by exact clinical observation and a detailed history of the 2 weeks prior to the onset of illness. PMID- 2184637 TI - Clinical usefulness of vinca alkaloid slow infusion in the treatment of chronic refractory idiopathic thrombocytopenic purpura: a multicenter cooperative study. AB - Thirty-eight patients with chronic refractory idiopathic thrombocytopenic purpura (ITP) were treated with weekly slow infusions of vincristine (0.02 to 0.04 mg/kg) or vinblastine (0.1 to 0.2 mg/kg). Twenty-two patients showed good to excellent responses after one to eight infusions. These responses were generally short, and lasted only in six patients after discontinuance of the therapy. The efficacy was comparable between vincristine and vinblastine. Neither the age, sex, duration of the disease, prior splenectomy nor combined use of adrenocortical steroids was likely to have influenced the therapeutic effect. Side effects such as peripheral neuropathy, alopecia, gastrointestinal symptoms and leukopenia occurred in 34 patients, and necessitated discontinuance of the therapy in eight patients. Slow infusions of vinca alkaloids can be an effective means of inducing platelet response in patients with chronic refractory ITP, but frequent side effects limit its clinical usefulness. PMID- 2184639 TI - Selection of medium for serum-free primary culture of adult rat hepatocytes. AB - To select a suitable medium for serum-free primary culture of adult rat hepatocytes, ten commercially-available synthetic media were compared for their ability to maintain the cells under serum-free and serum-supplemented conditions with special reference to attachment, survival and albumin secretion. It was found that Williams' medium E and DM-160 medium were the best among the ten media for maintaining hepatocytes under serum-free conditions in primary culture. PMID- 2184641 TI - [Medicine as a science of actions: consequences for psychiatry]. AB - The need for a theory is grounded on the heterogeneity of medicine: of basic situation, of medical subsystems and of praxis. The relationship between theory and practice in medicine should be considered as a task of theoretical reflection, beyond contexts, application and orientation. As a theory of theories -metatheory--its model lies closer to that of "action sciences" than of "object sciences", considered as paradigmatic forms of medicine. The relevance of these concepts to psychiatry is illustrated on the basis of the influence of behavioral sciences upon biomedicine, whose advancement rests with psychiatry. PMID- 2184640 TI - [Thematic Apperception Test: psychodiagnosis in heroin-dependent patients]. AB - The aim of our work is the search of some differential psychopathologic features or categories in the personality of the heroin addict, through the application of Murray TAT. Which, we try to contrast with another contributions carried out until the present time. On the other hand, other parameters of sociolaboral and demographic character have been valued. We do not detect a structure of uniform personality, through we observe clear differences with respect to people who are not dependent on drugs. According to the results we have found, there are a larger number of psychopathologic elements in the whole of the heroin addict personality, as a greater low self-esteem, a suicidal inclination, a problematic with authority models, an evasion of aggressiveness, feelings of anxiety and quiltiness, without being a universal pattern. PMID- 2184642 TI - [Psychologic reactions and psychiatric manifestations in HIV-positive patients]. AB - 88 patients presenting HIV seropositivity are studied at the Psychiatric Intersurgery of the Gregorio Maranon General Hospital in Madrid. All of them but 4 are drug addicts having acquired the illness through homo or heterosexual relations. After a wide bibliographical survey of the psychologic ann psychiatric aspects related to HIV seropositivity, clinical results are compared with those of the different authors who have dealt with the issue in the last years. Conclusions derived from the study are expressed at the end. PMID- 2184643 TI - [The EEG, CAT and alcoholism]. AB - The authors made a retrospective study of 355 patients with the diagnosis of "Dependence" (n = 324) and "Abuse" (n = 31) of alcohol. 205 of them were outpatients and 150 inpatients from the Medical Psychological and Psychiatric Department of the Clinical University Hospital in Valladolid, since 1980 to 1984. It's studied demand of psychiatric services in the alcoholic population, the sex (87.88% of men and 12.11% of women) the mean age (about 42 years in men and 37 years in women), the diagnosis of alcoholism ("Dependence" or "Abuse") and the characteristics of them ("Outpatients" or "Inpatients"). Later, they reviewed two usual instrumental tests in Psychiatry: The E.E.G., which was made in 261 patients (normal in 85%) and the C.A.T., made in 13 cases, with cerebral atrophy in the 61%. At last, a historical review was made about these instrumental tests in the alcoholic disease, and the authors propose, too, two decision trees for the differential diagnosis and the treatment of alcoholic convulsions. The study presented, also, 9 Tables, 2 Figures and 54 references. PMID- 2184644 TI - The principles of the up-to-date breast reduction. AB - In all cases of moderate- to high-grade hypertrophy of the breast, with or without ptosis, the author emphasizes that the reduction mammaplasty with L shaped suture lines proves to be an effective method that avoids unacceptable scars extending to the midline of the thorax, especially in the young patient. PMID- 2184645 TI - Robert Emmett "Pete" Moran: Washington's myth and master. PMID- 2184647 TI - PTCA of chronically occluded coronary arteries. AB - The occlusion of a coronary artery does not necessarily imply the existence of nonviable myocardium of that flow-dependent region, because the presence of a well developed collateral circulation may be a sufficient nutrient source. During an episode of increased demand for myocardial oxygen, this collateral blood supply may become insufficient, and symptoms of myocardial ischemia may arise. PTCA of the occluded vessel appears to be an attractive approach to relieve ischemia in this situation. The primary success of dilatation of totally occluded segments depends largely on the duration of the occlusion but also on anatomic factors such as total or functional occlusion, the length of the occluded segment, and good angiographic visualization of the coronary artery distal to the occlusion by collaterals. The primary success rate (+/- 60%) of PTCA of occluded vessels is lower than the success rate (greater than 90%) of PTCA of nonocclusive stenoses. Also the restenosis rate (+/- 40%) and subsequent recurrence rate of angina pectoris is higher, compared to the 30% restenosis rate after dilatation of conventional lesions. Newer percutaneous techniques such as lasers, newly designed guide wires, and intravascular imaging devices are necessary to increase the primary success rate. Whether these techniques will also improve the long term results remains uncertain. PMID- 2184646 TI - Mastopexy: modification of periwinkle shell operation. Ten years of experience. AB - Degrees I and II ptosis and atrophy of the female breast can definitively be corrected by the modified periwinkle shell operation. More problematic are the long-term results after correction of a degree III condition, especially when silastic prostheses for augmentation have been used. The long-term results can be optimized by a combination of dermal and glandular mastopexy and mammary implants. PMID- 2184648 TI - Percutaneous valvuloplasty as a treatment for aortic and mitral valve disease. PMID- 2184649 TI - Effects of nifedipine on myocardial perfusion during exercise in chronic stable angina pectoris. AB - Nifedipine may be effective in the treatment of stable angina by both decreasing myocardial oxygen demand and increasing myocardial oxygen supply. To determine the mechanism of action of nifedipine and its dose-response relation, 14 patients with stable angina were treated with nifedipine 10, 20 and 30 mg 4 times daily as single-agent therapy in a double-blind, randomized, placebo-controlled crossover trial. Treatment was continued for 1 week on each dose regimen and efficacy was determined using an exercise test at the end of each phase. Compared to placebo, a significant decrease of systolic blood pressure at peak exercise occurred with the nifedipine 20- and 30-mg regimens (p less than 0.05), accompanied by an increase in heart rate on the 10- and 20-mg regimens (p less than 0.005). There was no significant effect on the rate-pressure product compared to placebo at any exercise time on any of the nifedipine regimens. The times to onset of ST-segment depression and to angina were delayed significantly by all 3 dose regimens compared to placebo (p less than 0.02). There was a significant decrease in the magnitude of ST-segment depression at all exercise times by all dosage schedules of nifedipine compared with placebo (p less than 0.05), although there were no significant differences among the 3 dosage schedules. Data indicate that since nifedipine was effective in improving manifestations of myocardial ischemia during exercise without altering the double product at submaximal or maximal exercise, its beneficial mechanism of action may have been due to enhancing blood flow to ischemic zones or to favorably altering determinants of myocardial oxygen demand, which were not measured. PMID- 2184650 TI - Cardiovascular protective properties of indapamide. AB - Although indapamide has been used for many years as a first-line treatment of hypertension, it is only recently that some of its activities on the changes of the cardiovascular system, brought on by age and high blood pressure, have been studied. Indapamide appears to reduce blood pressure by a combined diuretic and direct vascular activity reducing vascular reactivity and total peripheral resistance. In addition, it has discrete effects on a number of interrelated systems that may protect the cardiovascular system. Indapamide reduces intracellular calcium levels, maintains magnesium ions, but reduces phosphate ions that may be involved in arterial rigidity. Circulating catecholamines remain unchanged but there is a reduction in normetanephrine, suggesting a reduction in sympathetic tone. It stimulates prostacyclin synthesis, increases levels of circulating prostacyclin, reduces platelet aggregation and stimulates the vasodilation elicited by endothelium-derived relaxing factor in the presence of bradykinin. In addition, it inhibits the formation of the vasoconstrictor prostanoid, thromboxane A2. The free radical scavenging activity of indapamide could also protect the vascular smooth muscle from the reperfusion injury of cerebral and myocardial ischemia. Indapamide induces a reduction in cerebral ischemia after carotid ligation. Unlike some other antihypertensives, it does not upset the high-density/low-density lipoprotein-cholesterol balance, reducing the possible risk of atherosclerosis. Moreover, the combination of binding to elastin and reduction in uptake of calcium and phosphate into the smooth muscle could be a mechanism for reducing arterial rigidity seen in the elderly and hypertensive patient. In hypertensive patients, these properties induce an improvement in arterial compliance, and in the long term a reduction in left ventricular hypertrophy. These pharmacologic and clinical results, together with a good antihypertensive efficacy and acceptability, suggest that indapamide may be a preferential agent in the long-term cardiovascular protection of the hypertensive patient. PMID- 2184651 TI - Cardiovascular effects of antihypertensive drugs--involvement in the therapeutic choice. AB - Hypertensive patients are at an increased risk of developing cerebrovascular and cardiovascular disease. Treatment has resulted in a substantial reduction in cerebrovascular deaths but not in cardiovascular mortality. As the number of deaths from myocardial infarction exceeds the sum of all other hypertension related mortalities, these results are disappointing. The hypothesis that metabolic side effects of many antihypertensive drugs offset the potential benefit of decreasing blood pressure is of particular interest. In established hypertension there is an increase in total peripheral resistance. Long-term therapy with diuretics decreases vascular resistance. This is also evident with dihydropyridine calcium antagonists, vasodilators, angiotensin-converting enzyme inhibitors and alpha blockers. In patients with hypertension, an increased wall to lumen ratio occurs in resistance vessels where mechanisms such as smooth muscle hypertrophy and increased amounts of elastin and collagen are present. In small resistance vessels, long-term antihypertensive therapy has a positive effect, but the effect in large arteries is variable. PMID- 2184653 TI - Long-term diuretic therapy and renal function in essential arterial hypertension. AB - One of the main objectives of antihypertensive therapy is to preserve renal function from the deleterious effects of elevated blood pressure. Diuretics alone or in combination are effective for the treatment of arterial hypertension. Nevertheless, their use is accompanied by unwanted biochemical side effects, which have been attributed to their renal effects. During the last 10 years a group of 211 patients, diagnosed as having essential hypertension, were followed up. During the follow-up, they received a stepped-care therapeutic regimen consisting of nonpharmacologic measures (group 1), hydrochlorothiazide and amiloride (group 2), propranolol (group 3) and, if necessary, hydralazine (group 4). During the study, blood pressure remained within comparable, well-controlled levels in the 4 groups of patients. A progressive elevation of the levels of total serum cholesterol and glucose was observed in every group. The elevation attained statistical significance (p less than 0.01) after 4 years of therapy in those groups receiving the diuretic alone or in combination. Nevertheless, after 8 years of follow-up, the increment observed in these 2 parameters did not differ when patients in group 1 were compared with those in the remaining groups, indicating that thiazide diuretics could contribute to the earlier appearance of forthcoming events. Serum potassium levels were significantly lower (p less than 0.01) in groups 2 and 3 than in group 1. At the same time, we have observed the progressive appearance of clinically relevant proteinuria in 15.2% of patients, and the range of protein excretion ranged from 350 to 3,700 mg/24 hours. The appearance of proteinuria did not depend on the lack of control of blood pressure, nor on the different therapeutic requirements but was accompanied by a progressive decrease in creatinine clearance. The consequences of the renal effects of diuretics are of great importance during long-term therapy. The present results indicate that diuretics preempt the appearance of a forthcoming increase in serum glucose and cholesterol, and lessen the clinical relevance of these events.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2184652 TI - Role of metabolic risk factors in cardiovascular prognosis of systemic hypertension. AB - There is an increasing awareness of the need to manage multiple risk factors in hypertensive patients, and of possible adverse metabolic effects of antihypertensive drugs which may counteract their ability to reduce the risk of cardiovascular disease. Data collected from the Austin Hospital Hypertension Clinic support previous observations that the incidence of cardiovascular risk factors such as plasma lipid abnormalities are high in hypertensive patients, and although it is becoming easier to control blood pressure in these patients, modification of other risk factors is difficult. The use of diuretics in doses lower than those conventionally prescribed has been advocated as a means of reducing the adverse metabolic effects. However, data from this study suggest that although low-dose hydrochlorothiazide therapy (25 to 50 mg/day) may be as effective as conventional doses of captopril in reducing blood pressure, adverse metabolic effects on plasma potassium, glucose and uric acid levels remain a problem. Indapamide, a relatively new diuretic when used at a fixed dose (2.5 mg/day), appears to be devoid of significant adverse metabolic effects and is a useful alternative to thiazide diuretics. An integrated approach to the management of multiple cardiovascular risk factors is important in hypertensive patients and should include non-pharmacologic methods and the selection of antihypertensive drugs that do not have adverse metabolic effects. PMID- 2184654 TI - Clinical efficacy and quality of life with indapamide alone or in combination with beta blockers or angiotensin-converting enzyme inhibitors. AB - A multicenter study was performed to assess the efficacy and the acceptability of indapamide in hypertensive patients previously untreated, or treated and unsatisfactorily controlled with either angiotensin-converting enzyme (ACE) inhibitor or beta-blocking therapy. Four centers participated in the study, which included patients whose supine diastolic blood pressure was between 95 and 115 mmHg with no treatment (group I, n = 40), those taking captopril (group II, n = 40) or those taking propranolol (group III, n = 40). After a 2-week single-blind placebo run-in period, patients received indapamide either alone (group I) or in combination with the previous therapy (groups II and III) for 4 months. Blood pressure, heart rate, weight, and clinical and biochemical acceptability were measured before and after 2 and 4 months of treatment. At the same time points, quality of life was determined using standardized questionnaires completed by the patient (20 items) and the physician (10 items) and a visual analog scale completed by the patient. In all groups, administration of indapamide induced a clinically and statistically significant reduction in both systolic and diastolic blood pressures in the supine position after 2 months. Indapamide alone controlled blood pressure in 82% of the patients previously untreated, and indapamide in combined therapy controlled blood pressure, respectively, in 67 and 85% of patients previously uncontrolled with ACE inhibitors or beta blockers. In all groups, questionnaires on quality of life showed a progressive and significant improvement in general well-being. After 4 months of treatment, the percentage of improvement in the physician questionnaire was 77.1% in group I, 60.6% in group II and 71.4% in group III.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2184655 TI - Long-term effects of indapamide: final results of a two-year Italian multicenter study in systemic hypertension. AB - To evaluate the antihypertensive efficacy and tolerability of a low-dose diuretic, indapamide, 2.5 mg once daily, was given to 248 patients with uncomplicated, mild to moderate hypertension for a period of 24 months. Blood pressure during sitting was 165 +/- 1/105 +/- 1 mmHg (mean +/- standard error of the mean) at the end of the placebo run-in period and 143 +/- 1/88 +/- 1 and 140 +/- 1/85 +/- 1 mmHg after 2 and 24 months, respectively; heart rate was clinically unmodified (from 77 +/- 1 to 75 +/- 1 beats/min). Total cholesterol, high-density cholesterol and serum triglycerides were unchanged, and uric acid increased significantly (from 292.0 +/- 6.5 to 377.7 +/- 56.5 mumols/liter). A mild reduction in serum potassium (-0.36 +/- 0.03 mmol/liter) was observed after 2 and 6 months of therapy; however, the degree of reduction appeared to be lower than that from reported studies with other thiazide diuretics. The incidence of hypokalemia (serum potassium less than 3.5 mmol/liter) was highest in northern Italy (17%), intermediate in the central region (14%) and lowest in southern Italy (2%), although the absolute reduction in serum potassium was similar in all the geographic areas. Blood glucose tolerance was unchanged despite the changes in serum potassium. The tolerability was good on the whole, with a tendency toward an improvement in the well-being of patients, most of whom were already asymptomatic before starting the study. PMID- 2184656 TI - Diuretics and the treatment of systemic hypertension. AB - Diuretics are still among the most frequently used antihypertensive drugs in the treatment of hypertension. Their pharmacologic and hemodynamic properties are based on the water and salt metabolism in the pathophysiology of high blood pressure. Initially, there is a reduction of plasma and extracellular fluid volume; cardiac output also decreases. After this early phase, cardiac output returns to normal with an accompanying decrease in peripheral resistance so as to correct the underlying hemodynamic fault of the hypertensive state. Diuretics have a high therapeutic efficacy either as monotherapy or in combination with beta blockers, angiotensin-converting enzyme inhibitors or calcium antagonists. The main problem with the use of diuretics is related to their metabolic side effects, which are dose-related. Currently, there is a tendency to administer low dose diuretics, which result in fewer clinical and metabolic side effects, but with a continued antihypertensive efficacy. Therefore, low doses of diuretics can be recommended as initial therapy in the stepped-care approach of hypertension. PMID- 2184657 TI - Beneficial effects of indapamide on lipoproteins and apoproteins in ambulatory hypertensive patients. AB - Among the numerous risk factors for atherosclerosis, 2 are particularly important: hypertension and primary or secondary abnormalities of plasma lipids and lipoproteins. Antihypertensive treatments significantly decrease the risk of cerebrovascular accidents, renal failure or hypertensive cardiomyopathy, but they have little influence on coronary artery disease. It has been suggested that some antihypertensive agents may have deleterious effects by altering serum lipoproteins and this may override the benefit of blood pressure reduction. Diuretics increase the blood concentration of total cholesterol, low-density lipoproteins and triglycerides. Indapamide, a methylindoline agent with vasodilator activity, has no adverse lipid effects. Twenty-six studies have clearly demonstrated that indapamide appears to be unique among diuretics because of an absence of adverse lipid effects. In some studies indapamide significantly increased high-density lipoprotein cholesterol, apoproteins A1, A2 and apoprotein E. When a thiazide diuretic had been given previously, indapamide treatment normalized the lipid and lipoprotein profiles. The reason for the lack of adverse lipid effects of indapamide is discussed. Thus indapamide, 2.5 mg once daily, is effective and safe for the control of mild to moderate hypertension, both in young and older patients. It may be an optimal diuretic for use in normolipidemic or hyperlipidemic patients, as it increases high-density lipoprotein but not low density lipoprotein cholesterol. PMID- 2184658 TI - Nontypeable Haemophilus influenzae meningitis in an adolescent. PMID- 2184660 TI - The effect of 100% oxygen on the propagation of tracheobronchial injury during high-frequency and conventional mechanical ventilation. AB - We compared the histologic alterations in the tracheae and bronchi of 30 premature baboons that were ventilated with either 100% or prn (as needed) oxygen (the fraction of inspired oxygen necessary to maintain the PaO2 between 50 and 80 mm Hg). The baboons were treated with either conventional positive-pressure ventilation (7 were treated with 100%; 7, prn) or high-frequency oscillatory ventilation (8 were treated with 100%; 8, prn). We used a semiquantitative scoring system to grade tissue changes in the trachea, carina, and main-stem bronchi. The fraction of inspired oxygen for all prn animals fell to a plateau of approximately 0.28 after 36 hours, where it remained for the duration of the study. The 15 100% baboons were ventilated for a mean of 139 hours, while the 15 prn baboons were ventilated for a mean of 151 hours. The findings in all conventional and oscillator-ventilated animals were similar and characterized by squamous metaplasia, cilia loss, and goblet cell loss. For both methods of ventilation, there were no differences in the injury scores between 100% and prn oxygen-treated animals. We concluded that there were no additional tracheobronchial histologic changes with 100% oxygen compared with prn oxygen. PMID- 2184659 TI - Valine, isoleucine, and leucine. A new treatment for phenylketonuria. AB - Early treatment of phenylketonuria by dietary phenylalanine restriction prevents brain damage. Behavioral and cognitive deficits occur when serum phenylalanine levels increase. Administration of valine, isoleucine, and leucine to patients with phenylketonuria may inhibit entry of phenylalanine into the brain and reduce its toxic effects on the central nervous system. Sixteen adolescents and young adults with phenylketonuria participated in double-blind trials in which a valine, isoleucine, and leucine mixture or a control mixture was given for four 3 month periods. Biochemical and neuropsychologic tests were carried out before and at the end of each period. Time to completion of a test that required substantial attention with mental processing (Attention Diagnostic Method) was faster during the valine, isoleucine, and leucine periods than during the control mixture periods. Improvement with valine, isoleucine, and leucine on a less demanding task (Continuous Performance Test) approached significance. These data lent support to the hypothesis that a regimen of valine, isoleucine, and leucine may help individuals unable to maintain low serum phenylalanine levels. PMID- 2184661 TI - Penicillin tolerance and erythromycin resistance of group A beta-hemolytic streptococci in Hawaii and the Philippines. AB - Penicillin remains the drug of choice for the treatment of streptococcal pharyngitis, with erythromycin as an alternative drug for individuals who cannot take penicillin. Two areas of concern in the management of streptococcal pharyngitis are (1) the prevalence of penicillin-tolerant group A beta-hemolytic streptococci reported in recent studies and (2) the high prevalence of erythromycin resistance in some geographic areas. We tested 305 isolates of group A beta-hemolytic streptococci from Hawaii and the Philippines for penicillin minimum inhibitory concentrations and minimum bactericidal concentrations and erythromycin minimum inhibitory concentrations. There was no evidence of penicillin resistance or tolerance. The prevalence of erythromycin-resistant and moderately susceptible isolates was 3.6% and 2.3%, respectively. There was a trend toward greater erythromycin resistance levels among Hawaiian isolates, but this was not statistically significant. PMID- 2184662 TI - Methodological issues in the epidemiological study of alcohol-drug problems: sources of confusion and misunderstanding. AB - Epidemiological research on psychoactive substance use disorders can and sometimes does lead to conclusions that are mutually conflicting. A current example is the apparent drop in substance use among adolescents in schools, with continuing high levels of substance-associated adolescent suicide, hospitalization, and crime. In an effort to clarify such differences, the author underscores the importance of understanding the three most common epidemiological methods. Each has different histories, advantages, liabilities, inherent value sets, and disparate-but-overlapping purposes. PMID- 2184663 TI - Immunohistochemical analysis of iris biopsy specimens from patients with Fuchs' heterochromic cyclitis. AB - Using immunohistochemical techniques, we analyzed iris biopsy specimens from eight patients with Fuchs' heterochromic cyclitis, seven patients with various other types of uveitis, and eight glaucoma patients without uveitis. No specific abnormalities related to Fuchs' heterochromic cyclitis could be detected. Four of the patients with Fuchs' heterochromic cyclitis and four of the patients with uveitis showed evidence of an inflammatory cell infiltrate, which was a mixture of interleukin-2 receptor-negative T helper and suppressor cells, B lymphocytes, and plasma cells. Only an occasional T lymphocyte could be seen in two of the patients without uveitis. The class II antigen HLA-DR was expressed on iris stromal cells in every patient in the Fuchs' heterochromic cyclitis group and uveitis group and in six of the patients in the nonuveitis group. In six of the Fuchs' heterochromic cyclitis patients, including two without immunohistochemical evidence of inflammatory cell infiltrate, histologic abnormalities were present on hematoxylin and eosin sections. PMID- 2184664 TI - Serologic tests in the diagnosis of presumed toxoplasmic retinochoroiditis. AB - We treated three patients who had documented Toxoplasma retinochoroiditis and negative immunofluorescent antibody toxoplasmosis titers (titer less than 1:16), positive Sabin-Feldman dye titers of 1:64, 1:16, and 1:64 in the three patients, respectively, and a positive enzyme-linked immunoassay titer of 1:256 in the one patient tested. In patients with negative immunofluorescent antibody toxoplasmosis titers, we recommend obtaining Sabin-Feldman or enzyme-linked immunoassay titers, or both, before excluding the diagnosis of ocular toxoplasmosis. PMID- 2184666 TI - American Occupational Therapy Foundation: milestones of a quarter century. PMID- 2184665 TI - Estrogen and progesterone receptors and human conjunctiva. AB - Freshly frozen conjunctival tissue from premenopausal and postmenopausal women and male subjects were processed for estrogen and progesterone receptors by using monoclonal antibodies and a peroxidase-antiperoxidase technique. No immunocytochemical staining was localized in the nuclei of the cells treated with the monoclonal antibodies to human estrogen receptor or human progesterone receptor in any of the conjunctival specimens, in contrast to the strongly positive staining in breast adenocarcinoma controls. Immunocytochemical staining disclosed no evidence for estrogen or progesterone receptors on cells of the ocular surface. PMID- 2184667 TI - A critical analysis of occupational therapy approaches for perceptual deficits in adults with brain injury. AB - Research about occupational therapy interventions for adult perceptual deficits is needed to examine the relative efficacy of different treatments and to scrutinize the theoretical assumptions underlying those treatments. The former purpose relates to providing optimal services to consumers; the latter, to advancing the knowledge base of the profession. Both of these purposes can be achieved if research questions are derived from the assumptions underlying treatments. This paper delineates those assumptions and suggests some research questions and strategies with which to test them. PMID- 2184668 TI - A stress management program: inpatient-to-outpatient continuity. AB - Stress is a factor in many modern illnesses. The development of coping skills to deal with stress is an occupational therapy goal for many patients. The program presented here uses stress management techniques to improve the situational coping skills of adult psychiatric patients. When discharged to the outpatient clinic, the patients in this program continue to learn and practice stress management techniques to increase relaxation and lessen anxiety. A case example is presented. PMID- 2184669 TI - The Curriculum Directors: influencing occupational therapy education, 1948-1964. AB - This paper depicts an important story in the history of occupational therapy. The story concerns a small group of women, known as the Curriculum Directors, whose influence prevailed in the growth and development of occupational therapy throughout the 1950s. The account is synthesized from both written history sources and oral history interviews with group members and their contemporaries. It characterizes the Curriculum Directors and describes their influence on the profession as well as others' perceptions of their accomplishments. This paper also chronicles the forces that emerged in reaction to the Curriculum Directors' authority and briefly details the dissolution of their power. PMID- 2184670 TI - A multidisciplinary approach to the development of competency standards and appropriate allocation for patients with dysphagia. PMID- 2184671 TI - Regulation of renin release and renal hemodynamics during acute and chronic verapamil administration. AB - The effects of short- and long-term administration of the calcium-entry blocker verapamil on regulation of renal hemodynamics and renin release were analyzed in anesthetized dogs at controlled levels of renal perfusion pressure between 110 and 60 mmHg. The following three groups of dogs were studied: a control group, an acutely treated verapamil group (initial dose of 150 micrograms/kg followed by 4 micrograms.kg-1.min-1), and a chronically treated verapamil group (240 mg per os twice each day). At 110 mmHg the renal blood flow (RBF) in the acutely and chronically treated groups was 53% greater than (P less than 0.03) and 79% greater than (P less than 0.01) that of the control group. Glomerular filtration rate (GFR) in the acutely and chronically treated groups was 64 and 92%, respectively, greater than (P less than 0.01 for both) that of the control group. Autoregulation of RBF and GFR was extremely effective in the control group, whereas it was severely impaired by acute and long-term treatment with verapamil. Renin release at 110 mmHg in the control and the acutely treated groups were similar, 3.36 +/- 0.96 and 4.46 +/- 0.64 U.min-1.g-1, respectively, although in the chronically treated group the rate of release was 8.89 +/- 2.60 U.min-1.g-1 (P less than 0.03). As perfusion pressure was reduced, the rate of release from the acutely treated group rose to higher levels than that of the control group; at 70 mmHg release from the acutely treated group was 88% greater than that of the control group (P less than 0.01). Verapamil profoundly alters regulation of renal hemodynamics and renin release and the effect is prominent during both short- and long-term administration. PMID- 2184672 TI - Regulation of renal transport processes and hemodynamics by macrophages and lymphocytes. AB - Inflammatory diseases of the renal glomerulus and interstitium are characterized by numerous alterations in renal glomerular hemodynamics and tubule transport processes. The cellular mechanisms underlying these changes have been theoretically attributed to nephron toxicity and destruction. However, recent studies suggest that many of the alterations in renal physiology may be mediated by specific immune cell-derived factors. Macrophages release a variety of cytokines on activation. One of these monokines, interleukin 1, induces a natriuresis by direct inhibition of collecting duct sodium reabsorption. Glomerular macrophages release highly vasoconstrictive compounds, including leukotriene D4 and thromboxane A2. Macrophages have now been demonstrated to migrate into the renal interstitium in diseases not previously considered to have an immunological component. Acute ureteral obstruction is characterized by a rapid infiltration of macrophages and lymphocytes into the kidney. Removal of the immune cell infiltrate in ureteral obstruction by irradiation markedly improves glomerular filtration rate and renal blood flow and partially corrects sodium and water excretion. Such immune modulation of renal function is likely to occur in a wide variety of diseases of the kidney, many of which do not involve a primary immunological insult. We propose that the abnormalities in renal hemodynamics and in the transport of fluid and electrolytes observed in states characterized by coexistence of immune cells among renal parenchymal cells may reflect a complex immune modulation of renal cell physiology. PMID- 2184673 TI - Effects of endothelin on renal function in dogs and rats. AB - Endothelin was infused for 20 min into the left renal artery of pentobarbital anesthetized dogs at 1 (n = 6) and 10 (n = 5) ng.min-1.kg-1. Renal blood flow (flow probe) increased 6 +/- 2 (SE) and 29 +/- 2% during the first 5 min of endothelin infusion and then slowly decreased to 86 +/- 3 and 29 +/- 2% of control at 20 min, respectively; the low renal blood flow persisted for at least 30 min after endothelin infusion, and there were no systemic effects of the peptide at either dose. These effects of endothelin on renal function were not altered by the angiotensin (ANG) II receptor antagonist, [Sar1,Thr8]ANG II. In the rat, endothelin was infused intravenously into three groups of pentobarbital anesthetized females for 30 min at 0.1 microgram.min-1.kg-1; five had endothelin only, six had either endothelin + [Sar1,Thr8]ANG II (n = 4, 1.0 micrograms.min 1.kg-1) or endothelin + saralasin (n = 2, 1 and 2 micrograms.kg-1.min-1), and five had endothelin + captopril (5 mg.h-1.kg-1). The inhibitors were infused throughout the entire experiment. During infusion of endothelin alone mean arterial blood pressure increased from 106 +/- 2 to 136 +/- 4 mmHg and the glomerular filtration rate decreased from 2.7 +/- 0.2 to 0.7 +/- 0.3 ml/min. Captopril attenuated the endothelin-induced changes in renal function but not the increase in mean arterial blood pressure, whereas the competitive ANG II receptor antagonists had no effect on either the systemic or renal actions of the peptide. These data demonstrate that endothelin is a potent renal vasoconstrictor with transient vasodilator effects and that the inhibition of kinin degradation may attenuate the renal actions of the peptide. PMID- 2184674 TI - Sodium homeostasis in conscious dogs after chronic cardiac denervation. AB - The ability to regulate renal sodium excretion after an acute reduction of total body sodium by peritoneal dialysis (PD) and subsequent dietary sodium repletion was investigated in 12 [6 intact, 6 chronically cardiac denervated (CD)] conscious, chronically instrumented dogs. For 10 days, balance experiments were performed with daily measurements of mean arterial blood pressure (MABP), right atrial pressure (RAP), and heart rate (HR). The prepared diet contained 0.5 (days 1-3 after PD) or 2.5 mmol Na.kg body wt-1.day-1 (control day and days 4-9 after PD). Control values were all similar in both groups except higher fasting plasma renin activities (PRA) were observed in the CD dogs [2.6 +/- 0.4 vs. 1.0 +/- 0.2 ng angiotensin I (ANG I).ml-1.h-1; P less than 0.05]. Days 1-4 after PD, RAP fell in both groups by 2-3 cmH2O, and renal sodium excretion decreased abruptly. PRA increased to 22.8 +/- 4.1 (intact) and 29.9 +/- 4.9 ng ANG I.ml-1.h-1 (CD dogs) (day 3 after PD). Both groups continued to retain sodium, and when it was available again, PRA decreased. After the amount of sodium lost by PD was regained, the intact dogs remained in a balanced equilibrium. In the CD dogs, PRA was still above control, and they retained sodium in excess (+ 1.9 +/- 0.1 mmol/kg body wt). We conclude that the cardiac nerves are not essential for stimulating PRA and sodium retention after an acute sodium deficit. However, the inhibition of PRA and the rapid adjustment of sodium balance during sodium repletion is impaired after cardiac denervation. PMID- 2184675 TI - In situ localization of renin and its mRNA in neonatal ureteral obstruction. AB - Angiotensin II is an important mediator of renal vasoconstriction resulting from chronic unilateral ureteral obstruction (UUO). Distribution of renin mRNA and immunoreactive renin (IR) was examined in kidneys of 1-mo-old Sprague-Dawley rats subjected to either sham operation (n = 21), left complete UUO (n = 21), or right uninephrectomy (UNX, n = 16) at 2 days of age. There were no differences among the three groups in mean arterial pressure or plasma renin activity. Unlike sham kidneys, in which IR was detected in less than 55% of juxtaglomerular apparatuses (JGA) and was confined to a juxtaglomerular location, IR in both kidneys of animals with UUO appeared in greater than 75% of JGA and extended along most of the length of the afferent arteriole (P less than 0.01). In contrast, IR in kidneys of UNX rats was localized to the JGA as in sham-operated animals. Compared with sham-operated kidneys, renal renin content was increased in the obstructed kidneys (P less than 0.01) but decreased in the intact opposite kidneys of UUO rats and in the remaining kidneys of UNX rats (P less than 0.05). Renin mRNA, detected by in situ hybridization histochemistry, was localized to the JGA in kidneys of all groups. However, the fraction of JGA containing detectable renin mRNA was higher in obstructed kidneys than in intact opposite, UNX, or sham kidneys (P less than 0.05). In conclusion, UUO alters intrarenal renin independent of the systemic renin-angiotensin system. The greater distribution of IR, increased renin content, and renin gene expression of kidneys with ipsilateral UUO are consistent with a role for renin-angiotensin in mediating the vasoconstriction resulting from UUO. PMID- 2184676 TI - Effects of chronic volume expansion and enalapril on chronic cyclosporine nephropathy. AB - Prolonged treatment with cyclosporine (CS) results in an irreversible renal lesion consisting of interstitial fibrosis and tubular atrophy, as well as prominent hyperplasia of the juxtaglomerular apparatus (JGA). Ischemia to the tubulointerstitial compartment caused by intense CS-mediated renal vasoconstriction may contribute significantly to the development of this lesion. To explore the potential role of volume contraction and activation of the renin angiotensin system (RAS) in the genesis of this lesion, we have employed a recently described rodent model of chronic cyclosporine nephropathy (CCN). Over 28 days of CS therapy, animals received plain drinking water, 1% saline, or enalapril (ENAL), 50 mg/l in drinking water. At the end of 28 days, Na+ balance in saline-treated animals was markedly positive, and plasma volume was increased; however, glomerular filtration rate (GFR) did not change, and the tubulointerstitial lesion and JGA hyperplasia as evaluated by morphometric techniques were unaffected. Enalapril-treated animals were relatively hypotensive with lower GFR than CS controls. Enalapril conferred no protection against the development of tubulointerstitial disease and exacerbated the development of JGA hyperplasia and hyperkalemia. We conclude that volume contraction is not an important contributor to the reduced GFR, tubulointerstitial lesion, or JGA hyperplasia associated with long-term CS treatment. Blockade of the RAS also conferred no protection against the development of tubulointerstitial disease but resulted in worsening of JGA hyperplasia and hyperkalemia. PMID- 2184677 TI - Effect of water intake on the progression of chronic renal failure in the 5/6 nephrectomized rat. AB - This study tests the possible influence of the urinary concentrating process and/or of vasopressin (AVP) on the progression of early chronic renal failure (CRF). Male Sprague-Dawley rats were submitted to 5/6 nephrectomy and were offered water ad libitum throughout the study. In addition, half of the rats (high water intake, HWI) received their food mixed with a water-rich agar gel. The other rats (normal water intake, NWI) ate the same amount of food plus agar in the usual dry powder form. This resulted in doubling the daily water ingestion in HWI. Renal function was studied for 10 wk and kidney morphology assessed thereafter. Increased water intake in HWI reduced solute-free water reabsorption and urine osmolality about threefold to 12 +/- 1 ml/day and 390 +/- 9 mosmol/kgH2O, respectively (week 5 as example). Hematocrit, plasma sodium, and plasma creatinine concentration were unchanged. The progressive increases in urinary protein excretion and in systolic blood pressure observed in this model of CRF were significantly slowed in HWI compared with NWI (at week 5, 8.6 +/- 1.8 vs. 23.1 +/- 6.2 mg protein/day and 142 +/- 8 vs. 167 +/- 10 mmHg, respectively). Remnant kidney weight per unit body weight was 21% lower in HWI than in NWI (P less than 0.02). Incidence of glomerulosclerosis was also reduced and was correlated with kidney weight (P less than 0.01). AVP plasma level (PAVP) and plasma renin activity (PRA) were measured in additional rats. PAVP was about twofold higher (P less than 0.05) and PRA twofold lower (P less than 0.001) in rats with 5/6 nephrectomy than in control rats with two kidneys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2184678 TI - Flow-dependent vasodilation of brachial artery in essential hypertension. AB - Brachial artery hemodynamics including brachial artery diameter (D) and local blood flow velocity (V) was studied in 15 normotensive subjects (NT) and 19 age matched hypertensive patients (HT) at rest using a bidimensional pulsed Doppler system during a 2-min period of distal circulatory occlusion and during reactive hyperemia. Kinetics of changes in V and D were determined during successive and reproducible maneuvers. V and D decreased significantly during distal circulatory occlusion in both groups. During reactive hyperemia, V reached similar maximum values in both groups, and D increased significantly in NT and HT. Changes in D during reactive hyperemia were positively and significantly correlated with changes in V recorded at the same level. No significant difference was found between the two groups. These results demonstrate noninvasively that there are velocity-dependent variations in the diameter of a large artery in humans and suggest that velocity-dependent vasodilation of the brachial artery is not impaired in essential hypertension. PMID- 2184679 TI - Effect of blood filling in intramyocardial vessels on coronary arterial inflow. AB - The influence of the filling condition of the unstressed volume (UV) of intramyocardial vessels on the diastolic coronary arterial pressure-flow relationship was analyzed. UV is defined as the blood volume at zero transmural pressure. In seven anesthetized, paced dogs with induced heart block, coronary artery inflow was occluded so that blood in the UV was displaced into the coronary vein by myocardial contraction. After pacing was turned off, coronary perfusion pressure was increased stepwise to seven target pressures (20-90 mmHg). After reperfusion, left anterior descending coronary arterial (LAD) flow reached an initial quasi-steady level, but great cardiac venous (GCV) flow was absent (UV unfilled phase). With reappearance of the GCV flow (UV-filled phase), LAD flow decreased to a final steady level. Pressure-flow relationships during both phases were linear (r = 0.97-0.99). The inverse of the slope of the pressure-flow relationship during the UV-filled phase, 0.69 +/- 0.08 mmHg.min.ml-1, was significantly higher than that during the UV-unfilled phase, 0.55 +/- 0.06 mmHg.min.ml-1 (P less than 0.01), although the zero-flow pressure intercepts were similar (18.9 +/- 1.8 mmHg for UV filled vs. 19.9 +/- 2.2 for UV unfilled). These results indicate that diastolic coronary arterial inflow is impeded by a blood volume within intramyocardial vessels that exceeds the UV. PMID- 2184680 TI - Myocardial adaptation to creatine deficiency in rats fed with beta guanidinopropionic acid, a creatine analogue. AB - A creatine analogue, beta-guanidinopropionic acid (GPA), was fed to 12 young rats for several weeks. Another 12 animals were kept in the same conditions and age matched. Six pairs of animals were used to measure some energetic and mechanical parameters of the isovolumic perfused heart and to measure the accumulation of the phosphorylated form of GPA (GPAP) by 31P-nuclear magnetic resonance (NMR) spectroscopy. As a result of GPAP accumulation, phosphocreatine and ATP content decreased by 90 and 40%, respectively, and mechanical performance was impaired. Six other pairs of animals were used to assess the mechanical performances of Triton X-100-skinned fibers and the myosin isoenzyme distribution. It was found that the maximal force, Ca and ATP sensitivities, and myofibrillar creatine kinase efficacy of creatine-depleted hearts were similar to control values. There was, however, a decrease in the rate of cross-bridge cycling, and the isoenzymic expression of myosin was changed from the fast myosin V1 to the slower forms V2 and V3. In all animals, hypertrophy was observed in both right and left ventricles. We conclude that rat hearts subjected to a slow and persistent decrease in creatine and phosphocreatine respond with both quantitative and qualitative changes. These alterations, which most probably lead to an improvement in the economy of cardiac contraction, are nonetheless not sufficient to maintain maximal force. PMID- 2184681 TI - Endotoxin inhibits contraction of vascular smooth muscle in vitro. AB - Decreased responsiveness of the vasculature to vasoconstrictors has been implicated in the pathogenesis of endotoxic shock, yet the mechanism of diminished responsiveness has not been determined. In these studies, exposure of rat aortic rings to purified Escherichia coli lipopolysaccharide (endotoxin) in vitro inhibited subsequent contractions caused by vasoconstrictors. Contractions caused by the alpha-adrenoceptor agonist phenylephrine, as well as those induced by potassium depolarization, were depressed by endotoxin. The effect of endotoxin on vascular contractions was delayed. Phenylephrine-induced contractions were not decreased during a 1-h exposure to endotoxin (10 micrograms/ml), but they were markedly decreased when tested several hours after the exposure period. A large part of the inhibition caused by a 1-h exposure to endotoxin was endothelium dependent. In contrast, endotoxin inhibited contractions equally in rings with or without endothelium exposed to endotoxin for a longer period (3 h). The inhibitory effect of endotoxin was not affected by indomethacin, but it was eliminated in aortic rings treated with the protein synthesis inhibitor cycloheximide. These studies indicate that endotoxin potently inhibits vascular contraction in vitro. The effect of endotoxin is apparently independent of prostanoids but may involve protein synthesis and effects on both vascular smooth muscle and endothelial cells. PMID- 2184682 TI - In vivo endotoxin and IL-1 potentiate insulin secretion in pancreatic islets. AB - This study evaluated the in vivo effects of endotoxin and interleukin 1 (IL-1) on in vitro insulin secretion from perfused rat pancreases and isolated pancreatic islets. Glucose-induced insulin secretion was potentiated in pancreases obtained from rats 3 h after endotoxin or 30 min after IL-1. Studies using isolated pancreatic islets indicated that islet sensitivity to glucose was increased by either endotoxin or IL-1 to a similar extent, but there was no effect of endotoxin or IL-1 on the maximal insulin secretory response of islets to glucose. Insulin secretion was not potentiated in perfused pancreases obtained from rats only 30 min after treatment with endotoxin. These results suggest that in vivo treatment with either endotoxin or IL-1 potentiates insulin secretion by increasing islet sensitivity to glucose. In addition, because endotoxin is known to potently stimulate the production and secretion of IL-1 in vivo, the results lend support to the hypothesis that the effects of endotoxin on insulin secretion may be mediated partially by IL-1. PMID- 2184683 TI - Altered sensitivity of osmotically stimulated vasopressin release in quadriplegic subjects. AB - Osmoregulation of vasopressin release was studied in 15 quadriplegic subjects (Quad) and 7 healthy control subjects (Con). Hypertonic NaCl (0.85 M) was infused intravenously (0.05 ml.kg-1.min-1) over 90 min in studies on supine subjects and in comparable studies on the same subjects erect (sitting). Erect posture in Quad, but not in Con, was accompanied by orthostatic reductions in arterial blood pressure and by significantly increased plasma aldosterone (P less than 0.001) and cortisol (P less than 0.001) concentrations and increased plasma renin activity (P less than 0.025). Changes in plasma arginine vasopressin concentration (PAVP) during hypertonic NaCl infusions were also greater in erect than in supine Quad (P less than 0.005), despite identical changes in plasma osmolality (Posm). Linear regression analysis of the PAVP/Posm relationship during hypertonic NaCl infusions showed highly significant correlations (P less than 0.0002) in both Quad and Con. Mean slope values for regression lines, however, were significantly higher in erect than in supine Quad (P less than 0.005) but did not differ in relation to posture in Con. Differences in posture were not associated with differences in abscissal intercepts in either Quad or Con. These studies show significant alterations in the sensitivity of osmotically stimulated vasopressin release related to differences in posture in Quad, characterized by enhanced sensitivity in erect posture due to nonosmotic stimuli not evident in Con. PMID- 2184684 TI - Regional hemodynamic effects of endothelin-2 and sarafotoxin-S6b in conscious rats. AB - Regional hemodynamic responses to bolus doses (4 and 40 pmol) and 60-min infusions (12 and 120 pmol/h) of endothelin-2 (ET-2) and sarafotoxin-S6b (S6b) were measured in conscious Long-Evans and Brattleboro rats chronically instrumented with pulsed Doppler flow probes. In both strains of rat the two bolus doses of ET-2 and S6b peptides caused an initial fall in mean blood pressure (MBP). At the higher dose S6b caused a greater fall in MBP than ET-2. In Long-Evans rats the fall in MBP after S6b was associated with renal, mesenteric, and hindquarters vasodilatations; in Brattleboro rats there was no renal or mesenteric vasodilatation with S6b. The high dose of ET-2 caused early mesenteric vasoconstriction in both strains. After the initial fall in MBP there were dose dependent increases in MBP together with renal and mesenteric vasoconstrictions. These effects were generally greater after S6b than after ET-2 and no less marked in Brattleboro than in Long-Evans rats, indicating that release of endogenous vasopressin was not an indispensable component of the response. Infusions of the higher dose of ET-2 or S6b caused increases in MBP only, associated with renal, mesenteric, and hindquarters vasoconstrictions. The results indicate that S6b is a more potent stimulus than ET-2 of vasodilator mechanisms in vivo; despite this, S6b also exerts more marked vasoconstrictor effects than ET-2. PMID- 2184685 TI - Acetylcholinesterase inhibitor, pyridostigmine bromide, reduces skin blood flow in humans. AB - Five subjects exercised on a cycle ergometer for 30 min at 55% peak oxygen consumption on two occasions in an environmental test chamber (ambient temperature = 29 degrees C; dew point temperature = 10 degrees C). Pyridostigmine bromide (PYR), an acetylcholinesterase (AChE) inhibitor, was ingested (30 mg) approximately 150 min before one experiment, and no drug was administered during the other experiment (control). Red blood cell AChE inhibition averaged 40 (+/- 7)% during PYR treatment. Esophageal temperature (Tes), an eight site-derived mean skin temperature, forearm blood flow (FBF; venous occlusion plethysmography), skin blood flow (SkBF; laser-Doppler velocimetry), and metabolic rate (indirect calorimetry) were measured. SkBF decreased 37% after PYR treatment compared with control (P less than or equal to 0.05). The Tes threshold for initiation of cutaneous vasodilation was 36.8 (+/- 0.3) degrees C for the control treatment and 37.0 (+/- 0.3) degrees C for the PYR treatment (P less than or equal to 0.01). FBF was not significantly different between treatments, whereas heart rate was reduced by 7 and 9 beats/min during rest and exercise, respectively (P less than or equal to 0.01). The increased threshold for initiation of cutaneous vasodilation with AChE inhibition by PYR is compatible with nonthermal modulation of the control of thermoregulation through increased acetylcholine (ACh) accumulation. This could potentiate preganglionic transmission to enhance adrenergic vasoconstrictor tone. One suggested mechanism possible at the neuroeffector junction of the sweat gland may be that accumulated ACh diffusion across the adventitia of adjacent arterioles to muscarinic receptors initiates contraction of the smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2184686 TI - Ethanol attenuates endotoxin-enhanced glucose utilization. AB - Ethanol (EtOH) is known to alter various aspects of cellular metabolism. Among these, the blunting of the increased rate of glucose production and utilization by the host after the administration of endotoxin may be an important factor in the increased susceptibility to infections. Therefore the present study was conducted to determine which tissues are responsible for the attenuation of the endotoxin-induced increase in whole body glucose utilization after acute EtOH administration. In vivo glucose metabolic rate (Rg) of different organs was investigated in conscious rats by the tracer 2-deoxy-D-glucose technique. Rats received a slow intravenous bolus injection of EtOH (275 mg/100 g body wt of a 20% wt/vol solution) followed by a continuous infusion (25 mg/100 g body wt) that was maintained throughout the experimental period. Thirty minutes after initiation of the EtOH treatment, Escherichia coli endotoxin (100 micrograms/100 g body wt) was administered intravenously. Time-matched control animals received an equal volume of saline. EtOH alone affected Rg only in gastrocnemius muscle (30% decrease) and adipose tissue (twofold increase). Endotoxin alone increased Rg in all tissues examined except in heart and brain. Prior administration of EtOH inhibited the endotoxin-induced increased Rg in skeletal muscle (regardless of fiber type), ileum, liver, adipose tissue, and kidney, blunted the increase in spleen and lung, and did not alter the increased Rg in skin. Brain showed a 20% decrease in Rg in response to EtOH and endotoxin administration. The EtOH attenuated increase in glucose utilization in the macrophage-rich tissues of endotoxin-treated rats may be a reflection of an impaired capacity of these tissues to respond to infection. PMID- 2184687 TI - In search of a national agenda for international health problems. PMID- 2184688 TI - Characteristics of malaria transmission in Kataragama, Sri Lanka: a focus for immuno-epidemiological studies. AB - Parasitological and entomological parameters of malaria transmission were monitored for 17 months in 3,625 residents in a Plasmodium vivax malaria endemic region in southern Sri Lanka; the study area consisted of 7 contiguous villages where routine national malaria control operations were being conducted. Malaria was monitored in every resident; fever patients were screened and 4 periodical mass blood surveys were conducted. An annual malaria incidence rate of 23.1% was reported during the period: 9.3% was due to P. vivax and 13.8% was due to P. falciparum; there had been a recent epidemic of the latter in this region, whereas the P. falciparum incidence rate in the previous 10 years had been negligible. There was a wide seasonal fluctuation in the malaria incidence, with the peak incidence closely following the monsoon rains. The prevalence of malaria due to both species detected at the 4 mass blood surveys ranged from 0.98% (at low transmission) to 2.35% (at peak transmission periods). Adults and children developed acute clinical manifestations of malaria. Entomological measurements confirmed a low degree of endemicity with estimated inoculation rates of 0.0029 and 0.0109 (infectious bites/man/night) for P. vivax and P. falciparum, respectively. Several anopheline species contributed to the transmission, and the overall man biting rates (MBR) showed a marked seasonal variation. Malaria at Kataragama, typical of endemic areas of Sri Lanka, thus presents characteristics of "unstable" transmission. Malaria was clustered in the population. There was a low clinical tolerance to P. falciparum malaria, to which most had only been at risk, compared to P. vivax, to which most had had a life-long exposure. PMID- 2184689 TI - Differences in susceptibility among mouse strains to infection with Plasmodium berghei (ANKA clone) sporozoites and its relationship to protection by gamma irradiated sporozoites. AB - Three inbred mouse strains, C57BL/6 (H-2b), A/J (H-2a), and BALB/c (H-2d), and 1 outbred strain, CD-1, demonstrated differences in susceptibility to iv challenge with the ANKA clone of Plasmodium berghei. Mice were challenged with 100, 1,000, or 10,000 sporozoites, then evaluated daily beginning on day 4 for patency. CD-1 mice were further evaluated at challenge doses of 12,500, 25,000, and 50,000 sporozoites. C57BL/6 mice were the easiest to infect, with 90% becoming infected with 100 sporozoites. The outbred strain CD-1 was the most difficult to infect, requiring a challenge dose of 25,000 sporozoites/mouse in order to achieve a 100% infection rate. Mouse strains also demonstrated differences in their ability to be protected by intravenous immunization with gamma-irradiated sporozoites. A/J mice needed a minimum of 3 doses of irradiated sporozoites for protection against a challenge with 10,000 sporozoites. In contrast, BALB/c mice immunized with a single dose of 1,000 irradiated sporozoites are protected against a 10,000 sporozoite challenge. These data suggest that both infectivity and protection are genetically restricted and that susceptibility to infection may be inversely related to protection. PMID- 2184690 TI - A rapid sporozoite ELISA using 3,3',5,5'-tetramethylbenzidine as the substrate chromogen. AB - A modified version of the standard 2-site sporozoite enzyme-linked immunosorbent assay (ELISA) using 3,3',5,5'-tetramethylbenzidine (TMB) as the substrate chromogen solution was adapted for rapid detection and identification of Plasmodium falciparum and P. vivax circumsporozoite (CS) proteins. The TMB-ELISA was evaluated using sporozoites from experimentally infected mosquitoes and laboratory colonized uninfected mosquitoes. Our data indicate comparable sensitivity levels between the TMB-ELISA and the standard ELISA, i.e., 50 P. falciparum or P. vivax sporozoites/50 microliters of test solution. Reactions inherent to the method were specific and background reactivity was minimal. The TMB-ELISA is rapid (1 hr), simple, uses a minimal amount of monoclonal antibodies, and is suitable for use in a wide range of laboratories. PMID- 2184691 TI - Cell adhesion molecules. AB - Recently it has become recognized that cell adhesion is critical in many different cellular functions. The proteins involved in the cell-cell or cell matrix interactions are known as cell adhesion molecules (CAMs). This article reviews some of the most important CAMs and emphasizes their importance in dermatology and in skin diseases. PMID- 2184692 TI - Naming acquired melanocytic nevi. Unna's, Miescher's, Spitz's Clark's. AB - In order to have an integrated system to classify acquired melanocytic nevi, specifically those that evolve through junctional, compound, and dermal phases, we propose to name them for those who first recognized or popularized them: Unna, Miescher, Spitz, and Clark. Historical, philosophical, and semantic justifications for an eponymic classification of acquired melanocytic nevi are presented. PMID- 2184693 TI - [Perioperative infusion therapy in children]. AB - An incorrect fluid therapy can lead to serious complications considerably more rapidly in children, especially in newborns and infants, than in adults. The pediatric patient has a limited range of compensation for maintenance of fluid and electrolyte balance. Precise knowledge of the physiological age-dependent fluid balance, i.e. the large extracellular space, the developing renal function, the increased metabolism, the acid-base state, the electrolyte balance with the relatively higher sodium and chloride requirements must be the basis of an adequate fluid therapy. The basic fluid requirement (normal fluid and electrolyte requirement) varies with age and is influenced considerably by environmental conditions, body temperature and metabolism. For substitution of this basic fluid requirement one-third to one-half strength electrolyte solution in 5% dextrose is used, the amount depending on age. The perioperative fluid requirement, however, has to be calculated with due consideration for the characteristic changes in fluid and electrolyte balance during anaesthesia and surgery, the preoperative fasting period, drug effects of anesthetics, hormonal changes and ventilation; it is higher than the basic fluid requirement (infants 6-8 ml.kg-1.h-1, toddlers 4-6 ml.kg.h-1, schoolchildren 2-4 ml.kg-1.h-1). For intraoperative fluid therapy infusions with an increased sodium concentration (70-100 mmol/l) or Ringer's lactate (Na+ = 130 mmol/l) must be used. On no account must electrolyte-free solutions, e.g., 5-10% glucose, be used intraoperatively, as they can lead to water intoxication. The third-space requirements compensate for the additional losses by drainage, third-space deficits by evaporation and gastric and enteral secretions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2184694 TI - [Critical aspects of an outside evaluation of postoperative pain in infants. A placebo-controlled double-blind study of the question of the reliability and validity of the measurement system]. AB - Postoperative analgesia in infants and young children is a topic of growing interest in pediatric anesthesia. Two systems measuring postoperative pain in this group of patients have been offered recently: CHEOPS (Childrens Hospital of Eastern Ontario Pain Scale) by McGrath et al. and OPS (Objective Pain Scale) by Hannallah et al. and Broadman et al. [3, 7, 8]. Both systems are economical and not reactive, but their validity is not satisfying. The validity of CHEOPS is based on the statements of experienced nurses, using the method of convergent validation by an expert's assertion. Hannallah and Broadman et al. judged the validity of their objective pain scale for infants and young children by statements of juveniles between 13 and 18 years of age. McGrath et al. accepted the item of spontaneous verbal communication as useful in the CHEOPS, although no such verbal comment occurred in their study on interrater and inter-item correlations. The aim of the present study was to evaluate the statistical qualification of items for measurements of the intensity of postoperative pain in young children and to investigate some aspects of their validity. MATERIAL AND METHODS. The study was performed in 54 children of ASA groups I and II aged 29.2 +/- 10.7 months. They were included in the study if they were pain-free before the operation and had no signs and symptoms of neurologic disease. The following operations were accepted: herniorrhapy, orchidopexy, circumcision, and umbilical herniorrhaphy. Premedication and general anesthesia were standardized. The patients were premedicated with midazolam 0.5 mg/kg rectally and subsequent intramuscular injections of ketamine 2.0 mg/kg with atropine 0.01 mg/kg. Anesthesia was induced and maintained by inhalation of oxygen/nitrous oxide and halothane (FiO2 0.3). All children were intubated and ventilation was controlled during the operation. After the operation and under steady-state anesthesia with 0.5 vol.% halothane and spontaneous respiration, the children received either nalbuphine 0.1 mg/kg, piritramide 0.1 mg/kg, or placebo in a randomized and double-blind manner. Respiratory and circulatory parameters were recorded for 15 min before anesthesia was discontinued. Five minutes after halothane had been discontinued the first measurement of the childrens' behavior was started with four subsequent measurements at fixed time intervals of 15 min. The measuring system was based on the six items of CHEOPS complemented by five items related to the waking state because it was assumed that the waking state generally modulates the child's ability to demonstrate pain. The design of the study was accepted by the ethic committee with the provision that neither a sedative nor an analgesic drug should be withheld from any child if indicated. Therefore, all children who seemed to feel discomfort according to the subjective impression of the anesthetist received midazolam intraveneously to a maximal dose of 2 mg. All the behavioral data were included in a factor analysis (principal components)... PMID- 2184695 TI - Skeletal structural adaptations to mechanical usage (SATMU): 1. Redefining Wolff's law: the bone modeling problem. AB - From the nature of a bone's endload and its local surface strains, the theory computes a modeling operator, Gamma (gamma), that predicts whether mechanical factors will cause lamellar bone modeling drifts, and where and of what kind. A given mechanical bone strain history then provides a separate modeling rate function, M, to specify the rate of such modeling drifts as fractions of the largest possible ones. Multiplying the two functions, e.g., gamma.M, then predicts mechanically controlled bone modeling responses for cortical and trabecular bone, both quantitatively and qualitatively. The theory correctly predicts each of the 6 known "principal adaptations" of lamellar bone, which provide a critical test of any such theory for this organ. The theory accounts for biologic, biomechanical, and clinical-pathologic knowledge not available in Wolff's time nor accounted for by most biomechanicians since. Existing proven methods can provide all numerical data needed to satisfy the theory's mathematical equations and already suggest provisional values for most of them. Its originator views the theory as the kernel of more and better theories to come rather than a finished work, a kernel that suggests a new and in some respects novel logical framework for analysing the problems, and a kernel that invites critique, refinement, and/or exploitation by others. PMID- 2184696 TI - Skeletal structural adaptations to mechanical usage (SATMU): 2. Redefining Wolff's law: the remodeling problem. AB - Basic multicellular unit (BMU)-based remodeling of lamellar bone causes bone turnover, net gains and losses of bone on some bone surfaces or "envelopes," and a remodeling space comprising bone temporarily absent due to evolving resorption spaces and incomplete refilling of them by new bone. Those features depend a) on how many new BMU arise annually, b) on how much bone each BMU has resorbed and c) formed upon its completion, and d) on how long the typical BMU takes to become completed. Because a, b, and c have limiting or maximal values in life that direct and/or indirect effects of mechanical usage of the skeleton can change, the theory presented here derives mechanical usage functions that express what fractions of those maxima a given mechanical usage history allows to happen. The theory predicts some changes in bone formation, resorption, balance, turnover, and remodeling space that depend on how remodeling responds to the vigor of a subject's mechanical usage. The theory can predict specific effects of specific mechanical challenges that experiments can test, and it fits abundant published evidence. As the kernel of a new approach to the problem it awaits critique and refinement by others. It plus the 3-way rule can redefine Wolff's law conceptually and also in mathematical and quantifiable form. PMID- 2184697 TI - Skeletal structural adaptations to mechanical usage (SATMU): 4. Mechanical influences on intact fibrous tissues. AB - This paper proposes that the growth in length of living fibrous tissue structures (tendon, ligament, fascia) responds primarily to circulating systemic rather than mechanical factors. However, growth of the thickness of those structures responds primarily to their mechanical tension loads in the special sense that, when the tissue's typical peak mechanical strains exceed a threshold value, its cells begin to add new collagen to increase its thickness, strength, and tension stiffness. When subsequent peak strains reduce to the threshold value, then further additions of collagen stop. That process defines mechanically controlled modeling of fibrous tissues. The collagen in these tissues can also develop mechanical microdamage (MDx) under repeated tension load-deload cycles. Special maintenance mechanisms normally repair that MDx to prevent accumulations that would threaten structural integrity. As a result, spontaneous complete ruptures of these structures can happen when MDx production exceeds its repair. These maintenance mechanisms also prevent gradual stretching under continuous tension loads, a process the author suggests calling creep compensation. When the creep compensation mechanism becomes incompetent, structures can stretch under continuous loads; when it becomes overactive, contractures can occur. The above meld of fact and inference provides the kernel of a general theory for the responses of the architecture and mechanical competence of intact fibrous tissues to mechanical usage. PMID- 2184698 TI - Vascular network in papillae of dog oral mucosa using corrosive resin casts with scanning electron microscopy. AB - The purpose of this study was to undertake a three-dimensional analysis of the vascular network of the lamina propria in the gingiva, alveolar mucosa, buccal mucosa, palate, and lingual mucosa of the dog. Using the corrosive resin casting technique, casts of the vascular network were prepared and examined by scanning electron microscopy. In the oral mucosa, larger arteries in the submucosa divide into smaller branches that enter the lamina propria. These branches form one or more layers of vessels at the base of the papillae of the lamina propria, the so called subpapillary vascular network. Here the vessels divide again and enter the papillae to form a subepithelial capillary network. The configuration of the capillary loops within each papilla of the lamina propria is determined by the shape of the papilla. The characteristic shape of the loops resembles a hairpin. The capillary loops in the lingual papillae are larger and more complex than capillary loops found elsewhere in the oral mucosa. The mucosa of the posterior portion of the hard palate, the soft palate, and the tongue contain many venous valves. PMID- 2184699 TI - Combined time-lapse cinematography and immuno-electron microscopy. AB - A method was developed to record interactions between mobile non-adherent immunocytes by time-lapse cinematography and then to study the same cells by immuno-electron microscopy, using monoclonal antibodies against surface components. For this purpose a modified stage was designed to fit an inverted microscope. The attachment included a device to cool the culture chamber with N2 gas, a micro-injector for monoclonal antibody and immuno-gold treatment, and two pairs of washing needles to change the medium without disturbance. The technique was first employed to study the formation of aggregates around the antigen presenting cells in cultures containing cells from hyper-immunized animals. Recently peripheral blood cells from normal subjects and patients with immune deficiency syndromes were stimulated with pokeweed mitogen, cluster formation was recorded, and the cells were processed for immuno-electron microscopy. PMID- 2184700 TI - Perioperative management of the multiorgan donor. AB - Organ transplantation is a multidisciplinary specialty that has seen remarkable advances in the past two decades, in the tireless pursuit of providing life saving therapy for patients suffering from end-stage organ failure. As the scientific basis and clinical practice of organ transplantation continues to evolve, it becomes increasingly apparent that "what was inconceivable yesterday, and barely achievable today, becomes routine tomorrow" (73). PMID- 2184701 TI - Alfentanil and delayed respiratory depression: case studies and review. PMID- 2184702 TI - Ontogeny and expression of chicken A blood group antigens. AB - Expression of chicken red blood cell (RBC) surface antigens was studied by using a monoclonal antibody (ISU-cA) specific for chicken A blood group antigens. Erythrocytes were examined from embryos of 3-18 days of incubation and from chicks at hatch up to 21 weeks of age. Specific antigens were detected on embryonic RBC surfaces by immunofluorescence as early as 3 days of incubation. Antigenic expression was examined by both haemagglutination and immunofluorescence and found to increase with age from embryos to mature birds. The antigen concentration on the cell surface was found to be affected by genotype; heterozygotes had an intermediate level of antigen between that of the two parental genotypes. These data confirm the co-dominance that is observed with most blood group antigens. Flow cytometric analysis allowed confirmation that the entire erythrocyte population gradually increased in antigenic expression over time, rather than having an antigen-negative subpopulation being replaced by a positive subpopulation. PMID- 2184703 TI - [Analgesic and respiratory effects of nalbuphine during the immediate postoperative period in thoracotomy]. AB - As most patients undergoing pulmonary surgery by postero-lateral thoracotomy have decreased preoperative pulmonary function, efficient postoperative analgesia is mandatory. Nalbuphine, a new agonist-antagonist opioid analgesic, and nefopam were compared in a double blind trial involving 60 patients. Intravenous injections of 0.3 mg.kg-1 of either drug were started when the patient evaluated his pain as being above 60 mm on a visual scale graduated from 0 to 100 mm. Repeated injections were carried out at the same dose, at the patient's request, after a minimal interval of 3 h for nalbuphine, and 6 h for nefopam. Analgesia was assessed by the visual scale, and by the patient's verbal appraisal. The respiratory and cardiovascular repercussions were evaluated clinically, and by monitoring breathing rate, blood gases, systolic and diastolic blood pressures, heart rate, and consciousness. Nalbuphine provided a convenient analgesia to all patients whereas analgesia with nefopam was insufficient in 15 out of 30 patients. No significant respiratory depression with either drug occurred. Nefopam led to a 30% increase in heart rate for one hour (p less than 0.01). Whereas patients given nalbuphine were more drowsy, although easily aroused, (p less than 0.001), nefopam was responsible for adverse effects (sweating, nausea, tachycardia with pallor, vertigo, malaise) requiring the exclusion of 7 patients from the study. Nalbuphine, although not ideal, would therefore seem to be a better analgesic than nefopam in thoracotomy patients. PMID- 2184704 TI - [Clonidine: from the treatment of hypertension to its use in anesthesia. I. Main effects and mechanism of action of clonidine]. PMID- 2184705 TI - [Anesthesia and factor VII deficiency]. AB - A case is reported of a 17 year-old patient undergoing emergency internal fixation of a mandibular fracture after a road traffic accident. Routine preoperative blood analysis revealed an isolated deficiency in factor VII (33%), with a normal activated partial thromboplastin time and a reduced prothrombin level (50%). Because there was no previous history of an haemorrhagic diathesis, the surgical procedure was carried out without any factor VII replacement. The course of surgery was normal, with no abnormal blood loss. The possible causes of this deficiency, and its treatment are discussed. PMID- 2184706 TI - Local anesthesia in pediatric patients: topical TAC versus lidocaine. AB - Lacerations requiring sutures are a common surgical emergency in children. Traditional anesthesia prior to suturing has been intradermal lidocaine. TAC (0.5% tetracaine, 1:2,000 adrenalin, 11.8% cocaine) is a topically applied anesthetic. A randomized, placebo-controlled, double-blind clinical study was conducted to test the hypothesis that topical TAC and intradermal lidocaine are equally efficacious with respect to patient compliance with the suturing process, ie, anesthetic application and placement of sutures, and development of wound complications. Patients less than 18 years old, with lacerations 5 cm or less in length, located in well vascularized, nonmucous membrane areas were included. Patients were entered into the intradermal or topical groups; the intradermal group received lidocaine and the topical group was randomized to receive either TAC or placebo. One hundred fifty-one patients were enrolled in the study. There was no significant difference in the rates of successful initial anesthesia with TAC (89%) and lidocaine (79%). TAC was significantly better (P less than .002) with regard to patient compliance with the suturing process than lidocaine or placebo. Seventeen percent of patients who received placebo had initial anesthesia. These results suggest that TAC, when applied correctly, may be the preferred anesthetic for laceration repair in children. PMID- 2184707 TI - TAC topical anesthesia produces positive urine tests for cocaine. AB - The combination of tetracaine, adrenalin, and cocaine (TAC) has become increasingly popular as a topical anesthetic for the suturing of simple skin lacerations. The purpose of this study was to determine the effects of TAC on a urine drug test for cocaine. On the morning after the use of TAC, 14 of 18 patients (78%) studied had positive screening tests for benzoylecgonine (cocaine metabolite) by the enzyme multiplied immunoassay test (EMIT) method. All specimens also were analyzed by gas chromatography and mass spectrometry, the reference standard for analysis of drugs of abuse in urine, and 15 of the specimens (83%) were positive. Four of 18 positive specimens (22%) still had positive EMIT drug screens on the morning of the next day, an average of 36 hours after use of TAC. We recommend that physicians who use TAC solution as a local anesthetic caution their patients that they may fail a urine drug screen for cocaine if they are tested within 36 to 48 hours of the administration of the use of TAC. PMID- 2184708 TI - A microcomputer application curriculum for emergency medicine residents using computer-assisted instruction. AB - A microcomputer application curriculum using computer-assisted instruction was developed for emergency medicine residents. Other than introductory comments, the course was composed entirely of disk-based tutorials. No faculty time was necessary. Subjects covered included introduction to microcomputers, the disk operating system; word processing, data bases, and spread sheets. The entire course, including the tutorial floppy disks, was contained in one loose-leaf notebook. Residents who took the course were surveyed. The course took an average of three to six hours to complete. All found the course to be helpful, with word processing being the most useful module. The majority of residents thought that the course was so valuable that it should be given earlier in the residency. Thus, we have moved the course to the first postgraduate year, and the data base and spread-sheet modules have been made optional. The course is easily assembled, requires minimal faculty time, and can be modified to accommodate different hardware and software. PMID- 2184709 TI - Treatment of hypercholesterolemia in the elderly. PMID- 2184710 TI - Recipients' estates: a source of revenue for Medicaid? PMID- 2184711 TI - How best to teach women breast self-examination. A randomized controlled trial. AB - OBJECTIVE: To compare three methods for teaching breast self-examination. DESIGN: Randomized controlled trial with factorial design. SETTING: A general medicine group practice in a university hospital. PATIENTS: Continuing-care patients from 40 to 68 years of age. Of 456 eligible women, 156 refused participation, 300 were randomly assigned, 269 completed assigned interventions, and 260 completed the post-test 1 year later. INTERVENTIONS: One third of patients received nurse instruction stressing tactile skills (Mammacare group) (Mammatech Corporation, Gainesville, Florida); one third, traditional nurse instruction emphasizing technique (traditional group); and one third, no nurse instruction (control group). Half of each group received physician encouragement. MEASUREMENTS AND MAIN RESULTS: One year later, women in the Mammacare group found more lumps (mean, 57%; 95% CI, 54% to 60%) in manufactured breast models than did those in the traditional (mean, 47%; CI, 44% to 51%) and control (mean, 45%; CI, 42% to 48%) groups. Lump detection specificity was unaffected. Self-reported examination frequency rose in all groups, to 5.1 times per 6 months in the traditional group, 4.2 in the Mammacare group, and 3.9 in the control group. Physician encouragement did not improve sensitivity, specificity, or overall frequency. Women in the Mammacare group used more of seven examination techniques (4.9) than did those in the traditional (3.9) or control (3.2) groups (P less than 0.001). No group increased health care use or reported more overall worry about breast cancer. CONCLUSIONS: Mammacare instruction resulted in more long-term improved lump detection and examination technique use than did traditional instruction or physician encouragement. Breast self-examination instruction should emphasize lump detection skills. PMID- 2184712 TI - Hypercholesterolemia in elderly persons: resolving the treatment dilemma. AB - Of all age groups, men and women over 60 years of age have the highest prevalence of elevated serum cholesterol levels. Now that detection and treatment of high serum cholesterol levels are increasing, we need a rational approach to managing elevated cholesterol levels in elderly patients. Recent data indicate that high total cholesterol and low-density lipoprotein levels predict risk for coronary heart disease in patients over 60 years of age. However, selecting appropriate candidates for cholesterol-lowering therapy requires clinical judgment of the relative risks and benefits of each therapy and consideration of each patient's overall health status as well as of competing risks. Active medical management of high cholesterol levels, therefore, should be restricted to a limited fraction of elderly patients who are most likely to benefit from long-term therapy. The first line of treatment is diet modification; however, drug therapy for appropriate patients is not contraindicated because of age alone. PMID- 2184713 TI - Squamous cell carcinoma of the conjunctiva associated with benign mucous membrane pemphigoid. AB - A 67-year-old white man with benign mucous membrane pemphigoid OU developed, over a period of two months, a slightly pedunculated fleshy mass in the bulbar conjunctiva OS. The mass was excised and found histopathologically to be squamous cell carcinoma of the conjunctiva. The association of benign mucous membrane pemphigoid and squamous cell carcinoma of the conjunctiva has not been previously reported in the English literature to our knowledge. The significance of the simultaneous occurrence of these two conditions is discussed. PMID- 2184714 TI - Bilateral orbital infiltration as the initial sign of a peripheral T-cell lymphoma presenting in a leukemic phase. AB - We describe the clinical course of a young woman with a peripheral T-cell lymphoma who presented in a leukemic phase of the disease with an initial complaint of bilateral conjunctival swelling. PMID- 2184715 TI - [Quality of life of patients with hypertension treated with converting enzyme inhibitors]. AB - Converting enzyme inhibitors (CEIs) are widely used in treatment of essential hypertension. Large-scale clinical studies have shown that CEIs are well tolerated and cause fewer side effects than most other antihypertensive agents. The latter observation is fundamental for compliance with long-term treatment. There do exist, however, some side effects which although rare are not negligible. It is necessary though to distinguish between side effects linked to the class of therapeutic agents and those associated with particular structural features. Three types of side effects have been seen: 1) manifestations linked to inhibition of angiotensin II with systemic vasodilation (hypotension, vertigo) and decreased glomerular pressure (functional renal impairment) with preferred onset in renovascular hypertension; 2) potentiation of the bradykinin prostaglandin system which causes cutaneous eruptions and for reasons still poorly understood a cough which may justify discontinuance of treatment: 3) side effects for which the sulfydryl group is essentially responsible (rash, dysgeusia, neutropenia, proteinuria) and which basically appear to be linked to the use of high doses of captopril. In general terms, and bearing in mind the frequently dose-dependent character of the side effects, it is advisable to prescribe low doses of CEIs, and this therapeutic approach is strengthened by the possibility of concomitant use of a thiazide diuretic allowing improved antihypertensive effects, coupled to better reciprocal tolerance of the drugs. The end result is a better quality of life for the hypertensive subject, and hence improved compliance with long-term treatment. PMID- 2184716 TI - Guillain-Barre syndrome. AB - Guillain-Barre syndrome is an acute inflammatory demyelinative neuropathy usually presenting as a symmetric areflexic paralysis. An immunologic pathogenesis is likely. Early diagnosis is important since good supportive care and plasmapheresis can decrease morbidity and hasten recovery. PMID- 2184717 TI - Mammography screening for breast cancer. AB - There is now unequivocal evidence that screening with mammography reduces the mortality of breast cancer. This benefit will best be realized by a national screening program. Such programs require a meticulous organization with dedicated staff who are experienced in the management of screen-detected lesions. PMID- 2184718 TI - Digestion and absorption of dietary protein. AB - Dietary protein is normally assimilated in an efficient manner following the action of gastrointestinal proteases. A number of pathological conditions can alter this process, with deleterious nutritional consequences. PMID- 2184719 TI - Modulation of endothelial hemostatic properties: an active role in the host response. AB - As the cells forming the luminal vascular surface, endothelium regulates both barrier function, and pro- and anticoagulant reactions. Endothelial cells can do this by controlling the expression of cell surface molecules, such as receptors that regulate the hemostatic balance and those that affect permeability across the endothelial monolayer. This regulation occurs in response to environmental stimuli, such as cytokines, which have a central role in inflammation, or glucose modified proteins, which accumulate in the vasculature in aging and diabetes and are associated with vascular complications. The endothelial cell emerges as a dynamic regulator maintaining homeostasis in the quiescent state and contributing to the pathogenesis of vascular lesions in the stimulated state. PMID- 2184720 TI - Central nervous system effects of human immunodeficiency virus type 1. AB - Following its early entry into the central nervous system (CNS), HIV-1 alters cerebral cell architecture and may subsequently affect higher cognitive functions, leading eventually in some patients to HIV-1 encephalopathy. The CNS may also be the target of opportunistic infections and malignancy secondary to HIV-1 immunosuppression. Studies at the cellular, anatomical, and behavioral levels present evidence for significant involvement of the CNS in HIV-1 disease, while initial reports of treatment strategies hold promise for providing some amelioration in affected individuals. PMID- 2184721 TI - Current issues in central venous catheter infection. AB - The majority of central venous line-associated infections are caused by organisms on the skin near the exit site gaining access to the intravascular segment of the catheter. A variety of strategies have been used in an effort to reduce catheter contamination, but one innovation--the semipermeable transparent dressing--may actually increase infection risk. On the other hand, new catheter materials and designs probably reduce the risk. There are only a limited number of well designed studies of the increasingly popular totally implantable catheter system and the multilumen line, but it appears that the former is associated with a low rate of infection, while the latter may be more hazardous than the single-lumen line. PMID- 2184722 TI - Screening for hypercholesterolemia. AB - The detection of individuals with hypercholesterolemia has received world-wide support as a means of determining who would benefit from dietary and pharmacologic interventions. However, the clinician or public health practitioner should be aware of several issues that must be resolved before cholesterol screening can attain maximal impact. This review examines whether hypercholesterolemia is a condition worthy of screening programs and discusses the promises and pitfalls of individual and mass screening approaches. PMID- 2184723 TI - Actinic injury. AB - Sun exposure has multiple well-documented acute and chronic effects of substantial medical importance. The most extensively studied of these are the effects on the skin. Acute effects include sunburn, phototoxic and photoallergic reactions, altered immunoreactivity, and a variety of photosensitivity disorders. Chronic effects include photoaging and photocarcinogenesis. Photoprotection is central to both prevention and treatment. PMID- 2184724 TI - Critical appraisal of therapeutic endoscopy in biliary tract diseases. AB - Endoscopic treatment (by sphincterotomy) is now the preferred method for patients with retained or recurrent bile duct stones after surgery. It is also applicable to many acutely ill or high-risk patients who have not undergone cholecystectomy. Endoscopic stenting is preferable to the percutaneous transhepatic method for palliation of malignant biliary obstruction in patients unfit or unsuitable for surgery. Balloon dilatation and stenting can be used for management of postoperative bile duct trauma and biliary fistulae, and in patients with dominant strictures in sclerosing cholangitis. Papillary stenosis and sphincter of Oddi dysfunction can be treated by sphincterotomy after careful patient selection. Endoscopy is a new and simpler form of surgery. A team approach including endoscopists, surgeons, and radiologists is essential for appropriate patient care and for objective evaluation of new methods. PMID- 2184725 TI - Continuous oxygen therapy for the chronically hypoxemic patient. AB - The effects of long-term continuous O2 therapy on chronically hypoxemic patients are well established. Such therapy remains the most important means of improving survival and quality of life of these patients. The mechanism by which O2 induces these beneficial effects is not well understood, and several factors probably are involved. Patients who show stable hypoxemia are candidates for long-term continuous O2 therapy. O2 should be administered at least 19 hours per day, including sleep hours, and in a dose sufficient to raise arterial PO2 to 65-80 mm Hg. Continuous O2 therapy virtually eliminates hypoxemic episodes during sleep or exercise. Nasal prongs are the usual method for delivering O2 on long-term basis, and portable O2 supply systems permit patients to use O2 continuously without significant restriction of their activities. PMID- 2184726 TI - Cellular mechanism for ischemic ventricular arrhythmias. AB - Two of the major ionic abnormalities found early in ischemia are (a) loss of potassium with an increase in the extracellular potassium ion concentration and (b) an increase in free cytosolic calcium. Both of these ionic abnormalities can powerfully predispose to the development of arrhythmias. PMID- 2184727 TI - Nonpharmacologic treatment of the Wolff-Parkinson-White syndrome and other supraventricular tachycardias. AB - Nonpharmacologic treatment using surgery or intracardiac catheter ablation can be used for several forms of supraventricular tachycardia. Surgery is highly successful in preventing recurrent tachyarrhythmias in patients with the Wolff Parkinson-White syndrome and can be recommended as first-line treatment in several situations. Catheter ablation of the atrioventricular conduction system combined with an implanted ventricular pacemaker can offer substantial relief to selected patients with drug-refractory atrial fibrillation. Technical advances in catheter ablation will undoubtedly lead to more widespread use of this form of therapy in supraventricular tachycardia. PMID- 2184728 TI - Artificial heart valves. AB - This overview of heart valve prostheses is based on a current review of clinical reports and focuses on the major complications that characterize long-term valve performance: thromboembolism, thrombosis, anti-coagulant-related bleeding, and structural failure. PMID- 2184729 TI - Molecular mechanisms of diuretic agents. AB - Recent identification of the renal epithelial cell ion transporters inhibited by diuretics allows physicians to select appropriate types and doses of diuretics. The desirable and undesirable clinical consequences of these molecular mechanisms of action can also be predicted. PMID- 2184730 TI - Clinical pharmacology of caffeine. AB - Caffeine is the most widely consumed stimulant drug in the world. This chapter reviews the human pharmacology of caffeine; the evidence for its role in causing human disease, including addiction; and its potential usefulness as a therapeutic agent. PMID- 2184731 TI - Effects of calcium channel blockers on renal function. AB - Calcium channel or entry blockers (CEBs) exert important vascular and tubular effects on the kidney. These renal effects include an enhancement of glomerular filtration rate (GFR), renal blood flow (RBF), and electrolyte excretion. Experimental studies in animals and humans indicate the potential therapeutic use of CEBs in several important clinical situations, for example attenuating the course of acute renal failure and slowing the progression of chronic renal failure. The latter effect appears to involve both the agent's antihypertensive effect and an additional cytoprotective effect. That CEBs help preserve renal function in renal transplantation has been shown in both animals and humans. In this setting, the effects of cyclosporine (CsA) and CEB on the immune system and on CsA hepatic metabolism are areas of importance for future research. PMID- 2184732 TI - Diabetic neuropathy. AB - Diabetic neuropathy, the most common peripheral neuropathy in the Western world, is responsible for most limb amputations and considerable morbidity in diabetic patients. Although it is a sequela to insulin deficiency and/or hyperglycemia, its exact pathogenetic mechanism remains unclear. Therapy is directed at early diagnosis, exclusion of other neuropathic disorders, prudent glucose control, and avoidance of secondary complications of neuropathy such as foot ulceration by aggressive foot care, hygiene, and patient education. PMID- 2184733 TI - The resurgence of acute rheumatic fever in the United States. AB - The incidence of acute rheumatic fever (ARF) had been declining in the United States for decades, and by the late 1970s ARF had become a rare disease in most areas of the country. The mid-1980s saw a resurgence of ARF, with reported outbreaks in Utah, Ohio, Pennsylvania, and military recruit camps in Missouri and California, as well as sporadic cases in many other communities. This review summarizes salient epidemiologic data related to the resurgence, explores some possible explanations for its occurrence, and discusses strategies for prevention of rheumatic fever now and in the future. PMID- 2184734 TI - Intestinal malabsorption syndromes. AB - This chapter is a review of selected causes of intestinal malabsorption. The pathogenesis and clinical features of malabsorption due to acquired immunodeficiency syndrome (AIDS), celiac sprue, and small bowel bacterial overgrowth are discussed, with emphasis on recent developments. The etiology and diagnostic challenges of malabsorptive disorders in the elderly are also reviewed. PMID- 2184735 TI - Treatment of the anemia of chronic renal failure with recombinant human erythropoietin. AB - The anemia of chronic renal failure can now be effectively treated with recombinant human erythropoietin when given in adequate doses. This hormone replacement therapy is associated with significant clinical benefits but it requires adequate iron stores for maximal effectiveness, it may result in elevation in diastolic blood pressure, and the response may be blunted by the presence of infection or inflammation. PMID- 2184736 TI - Peptide mediators of hypercalcemia in malignancy. AB - A parathyroid hormone-like peptide that probably causes hypercalcemia associated with solid tumors was recently characterized. It is a potent hypercalcemic and hypophosphatemic factor whose production is strongly associated with hypercalcemia and whose properties account for most aspects of the clinical syndrome. Diagnostic tests for this peptide have been developed. The parathyroid hormone-like peptide as well as other cytokines, such as tumor necrosis factor alpha, likely play a role in causing hypercalcemia in multiple myeloma and lymphomas. PMID- 2184737 TI - Cellular and molecular mechanisms of allograft rejection. PMID- 2184738 TI - Infections in child day care centers as they relate to internal medicine. AB - Internists should be aware of the increased frequency of most communicable diseases among parents and child care providers exposed to children attending child day care centers. Episodes of shigellosis and hepatitis A among adults in contact with children in day care centers should be promptly reported to public health authorities, since they may indicate the presence of a day care center outbreak for which effective control measures are available. Although effective treatment or intervention is limited or not available for many other infections acquired by adults from children in day care centers, significant illness may result in a minority of individuals at increased risk for infection with agents such as cytomegalovirus and varicella. Acute infectious diseases of children caused by organisms transmitted from day care center staff are less common and largely preventable by ensuring that staff are appropriately immunized and screened for tuberculosis. PMID- 2184739 TI - Intestinal barriers to bacteria and their toxins. AB - Immunologic and nonimmunologic processes work together to protect the host from the multitude of microorganisms residing within the intestinal lumen. Mechanical integrity of the intestinal epithelium, mucus in combination with secretory antibody, antimicrobial metabolites of indigenous microorganisms, and peristalsis each limit proliferation and systemic dissemination of enteric pathogens. Uptake of microorganisms by Peyer's patches and other intestinal lymphoid structures and translocation circumvent the mucosal barrier, especially in immunosuppressed individuals. Improved understanding of the composition and limitation of the intestinal barrier, coupled with advances in genetic engineering of immunogenic bacteria, development of oral delivery systems, and immunomodulators, now make enhancement of mucosal barriers feasible. PMID- 2184740 TI - Nonsurgical treatment of gallstone disease. AB - Gallstones can now be treated nonsurgically as well as surgically. The current view is that only symptomatic gallstones should be treated; of these, only cholesterol gallstones can be treated nonsurgically. Cholesterol gallstones in a functioning gallbladder will dissolve slowly when the secretion of unsaturated bile is induced by the ingestion of ursodiol or chenodiol, which are naturally occurring bile acids. Stone dissolution can be accelerated by increasing the surface area via extracorporeal shock wave lithotripsy, which fragments stones rapidly and safely, enhancing their dissolution rate. A technique is being developed in which a catheter is inserted into the gallbladder via either a percutaneous transhepatic or endoscopic route and an organic solvent such as methyl tert-butyl ether is instilled, dissolving the stones rapidly without major side effects. Gallstones will eventually recur in about half of the patients treated by these nonsurgical approaches, because the gallbladder is left in place and the fundamental pathogenic abnormalities associated with this common disease are not corrected. However, the rate of recurrence of symptomatic gallstone disease is lower. PMID- 2184741 TI - Neurologic consequences of cocaine use. AB - Neurologic consequences of cocaine use frequently present as medical emergencies in the form of stroke, repeated seizures, encephalopathy, acute headache, and unusual transient neurological deficits. The often fatal or disabling neurologic syndromes have only recently been recognized but are now well documented. Cocaine use is a significant cause of stroke in young adults, and the full, long-term ramifications of maternal cocaine use on the fetus will not be known for years to come. Unfortunately, there is not effective treatment other than abstinence, and our understanding of the pathophysiology of cocaine-associated neurologic illness remains limited. PMID- 2184742 TI - The gut as an endocrine organ. AB - Gut hormones serve as chemical messengers for communication between different cells of the gastrointestinal tract. Several technologic advances have contributed to the rapid evolution of peptide hormone biochemistry and physiology. Peptide hormones are potentially useful as diagnostic and therapeutic modalities in the practice of gastroenterology. PMID- 2184743 TI - How lymphocytes kill. AB - Cytotoxic T lymphocytes and natural killer cells are potent killers of target cells. These lymphocytes have large cytoplasmic granules containing cytotoxic peptides and other factors. Several of these molecules have been isolated and their functions elucidated. These molecules may be directly involved in the killing of virus-infected and transformed cells as well as in the development of cell-mediated autoimmune disorders. PMID- 2184744 TI - Porphyria and porphyrin metabolism. AB - Porphyrins, their reduced congeners (porphyrinogens), and their precursors are accumulated and excreted in excessive amounts in the porphyrias because of defects in the enzymes of heme biosynthesis. The nature of these defects is being defined using biochemical and molecular biological techniques. The principal clinical manifestations in the porphyrias, photocutaneous lesions and neurological dysfunction, are linked to the biochemical abnormalities, and appropriate therapeutic interventions have accordingly been developed. The exogenous administration of metalloporphyrins and porphyrin derivatives, unlike the harmful effects of porphyrins in the porphyrias, may be of use in some clinical conditions, such as the treatment of hyperbilirubinemic states and the detection and therapy of certain cancers. PMID- 2184745 TI - Treatment of hyperlipidemia. AB - The rationale of treatment to prevent or delay the onset of atherosclerotic disease is based upon recognition that a key process in atherogenesis is the uptake of certain lipoproteins by scavenger cells in the artery wall. These lipoproteins enter the artery wall from blood. Thus the risk of atherogenesis is linked to the concentrations of these lipoproteins in plasma. Although a number of processes involved in atherogenesis may ultimately yield to additional means of intervention, the current central strategy is to reduce levels of atherogenic lipoproteins in blood. This strategy draws support from several recent intervention trials, which have shown reduction of progression of coronary disease and, in one instance, reduced total mortality. Recent advances in therapy, including the advent of HMG CoA reductase inhibitors and the development of combined drug regimes of unprecedented effectiveness, now permit the reduction of plasma lipoprotein levels to the optimum in a majority of individuals. Rational selection of single-drug regimens and drug combinations is based on phenotypic characterization of lipoprotein disorders. The physician also needs to be aware of disease that can lead to secondary hyperlipoproteinemia so that the underlying disorders can be treated if possible. The treatment by diet of all individuals with hyperlipidemia or atherosclerotic disease is recommended. The decision to treat with drugs should involve consideration of risk factors such as the patient's sex, blood pressure, smoking habits, levels of HDL, and family history of atherosclerosis. PMID- 2184746 TI - Biology and clinical aspects of the hematopoietic growth factors. AB - Molecular cloning of the genes for several members of a family of glycoproteins, the hematopoietic growth factors (HGFs), has transformed experimental hematology. Molecular probes have been used to investigate the cellular source of the HGFs and the mechanism by which their genes are regulated. Recombinant purified HGFs have been used to investigate their functions in vitro, the binding characteristics of their receptors, and the isolation of certain receptor cDNAs. This increase in knowledge of the cellular biology of the HGFs has led to clinical trials of their efficacy. Specific HGFs or HGF combinations are likely to find a place in the management of several different bone marrow failure states. PMID- 2184747 TI - Immunopathogenesis and immunotherapy of type 1 diabetes. AB - Research in recent years has elucidated more clearly the genetic and immunopathogenic basis as well as the natural history of Type 1 diabetes mellitus. The development of Type 1 diabetes can be conceptually divided into stages, beginning in part with a human leukocyte antigen (HLA)-restricted genetic susceptibility. In some genetically susceptible subjects, a triggering event activates both cellular and humoral autoimmunity. Glucose-stimulated insulin secretion and beta cell mass diminish as anti-islet autoimmunity progresses. This process culminates in overt diabetes when only residual beta cell mass (estimated to be less than 10%) remains. Complete beta cell destruction follows within months to years of diagnosis. Most attempts at interrupting beta cell destruction have taken the form of broad immunosuppressive therapy begun at diagnosis when beta cell destruction is nearly complete. Greater understanding of early immune mediators and refinement of techniques to identify subjects at risk for Type 1 diabetes have set the stage for more specific immunomodulation targeted earlier in the course of the disease. We will review these recent advances in understanding the immunopathogenesis of Type 1 diabetes as they pertain to current and future trials of immunotherapy. PMID- 2184748 TI - Desmopressin: a nontransfusional hemostatic agent. AB - Desmopressin (1-deamino-8-D-arginine vasopressin, DDAVP) is a synthetic analogue of the antidiuretic hormone L-arginine vasopressin. Because it can raise circulating levels of Factor VIII and of von Willebrand's factor, DDAVP is used for nontransfusional treatment of mild and moderate hemophilia and von Willebrand's disease. DDAVP also shortens the prolonged skin bleeding time in patients with uremia, liver cirrhosis, and platelet dysfunctions and is given to prevent or stop excessive bleeding in such conditions. Finally, there is evidence that DDAVP can reduce blood loss and transfusion requirements during and after surgical operations in which blood losses are unusually large. Hence DDAVP is useful as a nontransfusional hemostatic agent in many of the bleeding disorders frequently encountered in clinical practice. PMID- 2184749 TI - Pathophysiologic strategies in the management of congestive heart failure. AB - The management of patients with congestive heart failure is based upon an understanding of the pathogenetic mechanisms. Therapy aimed at optimizing preload, decreasing afterload, and improving contractility can improve symptoms, and in some instances, improve survival. PMID- 2184750 TI - The pathophysiology of pleural effusions. AB - Two features of human parietal pleura explain its role in the formation and removal of pleural liquid and protein in the normal state: the proximity of the microvessels to the pleural surface and the presence of stomata situated between mesothelial cells. For pleural fluid to accumulate in disease, there must be increased production from increased hydrostatic pressure, decreased oncotic or pleural pressure, increased microvascular permeability, or peritoneal-pleural movement. The rate of formation must overwhelm lymphatic clearance, which may be decreased by hydrostatic forces or blocked by malignant infiltration. PMID- 2184751 TI - Management of hypertrophic cardiomyopathy. AB - Therapy of hypertrophic cardiomyopathy aspires to reduce symptoms, increase exercise tolerance, retard or prevent disease progression, and improve prognosis. Medical treatment with calcium antagonists and suppression of rhythm disturbances with amiodarone seem to be most effective. In patients who show no improvement, surgical treatment must be considered. PMID- 2184752 TI - Insulin receptor structure and function in normal and pathological conditions. AB - The insulin receptor is a large cell surface glycoprotein that concentrates insulin at the site of action and also initiates responses to insulin. The receptor is a disulfide-linked oligomer comprised of two alpha and two beta subunits. Signal transduction through the insulin receptor appears to require the activation of an intrinsic tyrosine-specific protein kinase activity. A variety of disorders, both acquired and genetic, are associated with the development of insulin resistance and are frequently the result of cellular defects in insulin receptor structure, function, and action. The recent cloning of several mutant receptors from patients with genetic forms of extreme insulin resistance has increased our understanding of insulin resistance on the molecular level. PMID- 2184753 TI - Mechanisms regulating the reactions of human hemoglobin with oxygen and carbon monoxide. PMID- 2184754 TI - The physiology of cilia and mucociliary interactions. PMID- 2184755 TI - Goblet cells secretion and mucogenesis. PMID- 2184756 TI - Immunoglobulin secretion in the airways. PMID- 2184757 TI - Ca2(+)-activated cell volume recovery mechanisms. PMID- 2184758 TI - Electrophysiology of the parietal cell. PMID- 2184759 TI - Permeable cell models in stimulus-secretion coupling. AB - A number of mechanical and chemical methods have been developed to achieve selective permeabilization of the plasma membrane. These methods have been applied to many cell types and have proven to be highly useful for studying stimulus-secretion coupling mechanisms. Thus far, this approach has contributed significantly to our understanding of phosphoinositide metabolism and the regulation of intracellular calcium. The permeabilization techniques also have contributed important information regarding cAMP-dependent pathways. In addition to studies of stimulus-secretion coupling, permeabilized cell preparations can be employed for investigations of enzyme activity in situ and the properties of intracellular organelles in general. Since cell permeabilization, particularly with chemical agents, is surprisingly easy, these techniques should find wide application for future studies. PMID- 2184760 TI - Role of ion movements in neutrophil activation. PMID- 2184761 TI - Functional analysis of the modes of anion transport in neutrophils and HL-60 cells. PMID- 2184762 TI - Ionic mechanisms of cell volume regulation in leukocytes. PMID- 2184763 TI - Ca2+ as a second messenger within mitochondria of the heart and other tissues. PMID- 2184764 TI - Cytoplasmic [Ca2+] in mammalian ventricle: dynamic control by cellular processes. AB - A quantitative reconstruction of [Ca2+]i transients is the desired goal, but that goal has yet to be reached. It will be reached by solving Equation 2., once an adequate mathematical description of all its terms is obtained. If computed [Ca2+]i transients match closely those recorded under many experimental conditions, then we can be confident that our understanding of the cellular processes that control [Ca2+]i is correct. The SL Ca2+ ATPase and the SL Ca2+ leak do not make an important contribution on a given beat. All the available data, physiologic and biochemical, indicate clearly that the Ca2+ fluxes via the SL Ca2(+)-ATPase and SL Ca2(+)-leak pathways are small in comparison to others. Over many beats, however, the fluxes through these pathways will contribute to loading of the SR with Ca2+. In the abnormal case of resting cardiac muscle, [Ca2+]i will be determined by the balance between Ca2+ influx via leak and Ca2+ efflux via Na/Ca exchange and SL Ca2+ ATPase. There is an emerging consensus that the amount of Ca2+ entering via Na/Ca exchange during normal activity is small. This consensus derives from direct observation of changes in [Ca2+]i attributable to Na/Ca exchange, from computations that utilize new quantitative data on the current-voltage relation of the exchanger and on the quantitative relationship of exchanger current to [Ca2+]i. Clearly, the efflux of Ca2+ via Na/Ca exchange on each beat is significant. From theory and the fact that SL Ca2+ pumping is small, the efflux of Ca2+ via the exchanger must equal the Ca2+ influx through SL Ca2+ channels, but experimental studies have not yet verified this quantitatively. All the studies, recent and older, indicate that the [Ca2+]i transient in all mammalian species is dominated by Ca2+ released from SR. Even in the rat, widely believed to be the species most dependent on SR, the Ca2+ current contributes measurable Ca2+ (24). Provided that the SR is not depleted by rest, it is the major cellular entity that determines the [Ca2+]i transient in mammalian ventricular tissue on a given beat. Quantitative knowledge of the flux of Ca2+ from it, required for evaluating theories of excitation-contraction coupling, still awaits determination. PMID- 2184765 TI - Free radicals and their involvement during long-term myocardial ischemia and reperfusion. PMID- 2184766 TI - Load and length regulation of cardiac energetics. AB - Crossbridge cycling and consequent energy utilization during contraction are subject to physiologic regulation by load and length; the length effect on the sensitivity of troponin C to a given [Ca2+]i is an important, newly defined mechanism for this length regulation in cardiac muscle. Further, energy utilization persists throughout the cardiac contraction, demonstrably for isometric contractions initiated at optimal length, and is continuously modulated by length changes during variably loaded twitch contractions. The extent, rate, and time of load-induced length changes during myocardial contraction appear to be the primary variables affecting crossbridge activity and energetics. Load and length regulation of the properties of the heart represents a remarkably simple and direct biological response to the physiologic input and role in this organ. This mechanism is utilized by the heart in response to its dynamic loading environment both for long-term adaptation of cardiac mass to chronic load alterations, as discussed here recently (23), and for short-term adaptation of cardiac mechanics and energetics to instantaneous load alterations, as discussed above. It is probably no coincidence, given their central physiologic importance, that both of these most basic adaptive responses of the heart are simultaneously coming to be understood at the molecular level. PMID- 2184767 TI - Modulation of leukocyte-mediated myocardial reperfusion injury. PMID- 2184768 TI - Calcium-dependent regulation of protein synthesis in intact mammalian cells. AB - Extensive bodies of literature describe protein synthesis and processing; the endocrinology and metabolic bases whereby a variety of hormonal, mechanical, and nutritional influences affect cell function and adaptive responses; and various regulatory mechanisms mediating concerted intracellular control. Nonetheless, our current understanding of the mechanisms responsible for the regulation and subordination of protein synthesis to the overall metabolic and stimulus-response status of the cell is inadequate. The endoplasmic reticulum is central to these concerns. Potential roles of the endoplasmic reticulum in the regulation of protein synthesis are largely unexplored. We have attempted in this rather speculative review, based largely on our own data, to project a view of the endoplasmic reticulum as moderating the rate of translation through a mechanism sensitive to sequestered Ca2+. Compensatory routes whereby cells accommodate to Ca2+ deprivation so as to resume reasonable rates of protein synthesis are seen also to focus on the endoplasmic reticulum. With additional research, the underlying relationships that exist among reticular Ca2+ storage, protein processing, and mechanisms of translational control should become more broadly evident. The prevailing view of Ca2+ as a regulator of cytosolic processes may require some extension if sequestered Ca2+ participates in biological control mechanisms emanating from the endoplasmic reticulum. In effect, a reciprocal relationship would presumably exist among processes supported by cytosolic free Ca2+ vs those promoted by sequestered stores of the cation. Speculatively, such reciprocity would allow the rapid diversion of energy from one set of processes to the other. Conceivably, chronic Ca2+ loading at sequestered sites may be related to certain cellular adaptive Ca2+ loading involving tissue hypertrophy. Potential examples of stretch-induced responses that could be cited include thickening of arteriolar smooth muscle walls in hypertension (8) and cardiac hypertrophy in aortic stenosis (46). PMID- 2184769 TI - Exocytosis. PMID- 2184770 TI - Respiratory and ionic regulation in invertebrates exposed to both water and air. PMID- 2184771 TI - Pathways to regulated exocytosis in neurons. PMID- 2184772 TI - Viral and cellular membrane fusion proteins. PMID- 2184773 TI - Transepithelial osmolality differences, hydraulic conductivities, and volume absorption in the proximal tubule. AB - The weight of current evidence indicates that the proximal tubule has a high transepithelial osmotic water permeability in the range of 3500-6000 microns/sec, which is attributable in large part to the high water permeabilities of the cell membranes. Water movement through these membranes may occur through specialized, proteinaceous channels that can be blocked by sulfhydryl reagents. The water channels probably exclude even the smallest solutes and allow only single file movement of the water molecules as do the water channels previously described in the red blood cell and vasopressin-responsive epithelia. If a significant fraction of the water flow also occurs through the junctional complexes, it seems likely that these junctions could be a site for solute solvent coupling which would contribute to solute absorption by solvent drag and which would be responsible for non-unity reflection coefficients for some solutes such as Na+ and Cl-. This possibility is still a matter of vigorous debate. Since the transepithelial water permeability is high, only a very small osmolality difference (1-10 mOsM) is required to drive normally observed rates of volume absorption both in vivo and in vitro. The osmolality difference is produced at least in part by dilution of the luminal fluid and is possibly augmented by the development of interstitial hyperosmolality because of the rapid transport of preferentially absorbed solutes. In the future it is likely that the most important work in this field will relate to the factors that alter transepithelial water permeability and the solute and water permeabilities of the junctional complexes. Investigation in this area is essential in understanding how changes in capillary and interstitial hydrostatic and colloid osmotic pressure may affect volume absorption. PMID- 2184774 TI - Regulation of the predominant renal medullary organic solutes in vivo. AB - The predominant organic solutes of the renal medulla have been hypothesized to osmotically balance extracellular NaCl and protect macromolecular function from the adverse effects of urea. The evidence for their long- and short-term physiologic significance in vivo has been reviewed. The organic solutes decrease acutely in response to diuresis with a time course similar to that observed for inorganic ion fluxes and therefore probably play an important role in short-term volume regulation. However, because organic solutes are slow to accumulate (even in the presence of high urea and sodium concentrations), their significance to the short-term physiologic function of renal medullary epithelia is in doubt and needs further investigation. The organic solutes may be more important to the long-term function and survival of renal medullary cells. PMID- 2184775 TI - Unusual aspects of calcium metabolism in aquatic animals. PMID- 2184776 TI - A family of POU-domain and Pit-1 tissue-specific transcription factors in pituitary and neuroendocrine development. AB - The anterior pituitary gland provides a model for investigating the molecular basis for the appearance of phenotypically distinct cell types, within an organ, a central question in development. The rat prolactin and growth hormone genes are selectively expressed in distinct cell types (lactotrophs and somatotrophs) of the anterior pituitary gland, which reflect differential mechanisms of gene activation or restriction because of interactions of multiple factors binding to these genes. We find that the pituitary-specific 33,000 dalton transcription factor, Pit-1, normally expressed in somatotrophs, lactotrophs, and thyrotrophs, can bind to and activate both growth hormone and prolactin promoters in vitro at levels even tenfold lower than those normally present in pituitary cells. In the case of the prolactin gene, high levels of expression in transgenic animals required two cis-active regions; a distal enhancer (-1.8 to -1.5 kb) and a proximal region (-422 to +33 bp). Each of these regions alone can direct low levels of fusion gene expression to prolactin-producing cell types in transgenic mice, but a synergistic interaction between these regions is necessary for high levels of expression. The initial appearance of the prolactin transgene expression closely follows the appearance of high levels of Pit-1, but later increases in expression coincident with appearance of mature lactotrophs suggest the operation of additional, critical positive factor(s). Unexpectedly, transgenes containing the distal enhancer removed from its normal context are expressed in both the prolactin-producing lactotrophs and the TSH-producing thyrotrophs, thereby suggesting that sequences flanking this enhancer are necessary to restrict expression to the correct cell type within the pituitary. These data indicate that distinct processes of gene activation and restriction are necessary for the fidelity of cell-type specific expression within an organ. Consistent with this model, we find that lactotroph cell lines that cannot express the growth hormone gene contain high levels of functional Pit-1. We suggest a large, highly related POU-domain gene family, potentially exceeding 100 members, has been conserved and expanded in evolution to meet the increasing requirements for more intricate patterns of cell phenotypes. The POU-domain subgroup of the homeodomain gene family, in concert with other homeodomain proteins and with other classes of transcription factors, is likely to contribute to the establishment of the mammalian neuroendocrine system. PMID- 2184777 TI - Regulation of inhibin synthesis in the rat ovary. AB - The lifespan of the female rodent is characterized by dynamic changes in the hormonal regulation of the reproductive axis. From the time ovarian follicular growth is initiated in peripubertal animals, through recruitment, ovulation and luteinization during the estrous cycle, to the quiescent follicular development of pregnancy, and ultimately to follicular exhaustion, tremendous changes in follicular architecture, hormonal responsiveness, steroid secretion, and inhibin and activin synthesis occur. Similar changes in both the biosynthetic functions and hormonal responsiveness of the pituitary are likely to occur. Some of the information on inhibin expression during the reproductive life-span of the rat reviewed here is summarized in a schematic fashion in Figure 3, which presents changes in serum FSH, ovarian inhibin production, and follicular development during different reproductive states. From recent observations regarding ovarian inhibin expression as a function of reproductive status, a partial picture of the complex interactions between steroid and peptide hormones necessary to maintain reproductive cyclicity in mammals is beginning to emerge. Study of the inhibin gene family and of other FSH-regulatory hormones is likely to further enhance our understanding of both normal reproductive processes and of reproductive disorders. PMID- 2184778 TI - Reverse genetics using transgenic mice. PMID- 2184779 TI - Flash photolysis studies of excitation-contraction coupling, regulation, and contraction in smooth muscle. AB - 1. Flash photolysis of caged compounds of phenylephrine, inositol 1, 4, 5 trisphosphate (InsP3), GTP gamma S, ATP, and CTP has been successfully used to study excitation-contraction coupling, contractile regulation, and contraction in smooth muscle. Major processes explored with this method were (a) the delay between agonist-receptor interaction and contraction and between the rise in InsP3, Ca2+ release and contraction; (b) the effect of myosin light chain phosphorylation on the rate of force development and the respective contributions of phosphorylation and crossbridge kinetics to differences between phasic and tonic smooth muscles; (c) the kinetics of the crossbridge cycle. We have also reviewed recent results obtained by other methods and bearing on the mechanisms of pharmacomechanical Ca2+ release and modulation of the Ca2+ sensitivity of the regulatory/contractile apparatus. 2. The long delay (1.5 at 22 degrees C) following activation of alpha 1-adrenergic receptors through photolysis of caged phenylephrine and the high Q10 of this process are consistent with the hypothesis that activation of phospholipase C is the major mechanism of alpha-adrenergic pharmacomechanical Ca2+ release. 3. The delay between photolysis of caged InsP3 and Ca2+ release is short: 30 ms or less, while the latency of contraction is significant (0.3-0.5 s at 22 degrees C) and similar to the lag between the rise in [Ca2+]i and force development in intact smooth muscles. The latency of contraction following photolysis of caged ATP in permeabilized muscles in rigor, in the presence of Ca2+ and calmodulin, is similar, about 0.2-0.5 s at 22 degrees C. 4. In muscles in which the myosin light chains are maintained in a phosphorylated state during rigor, photolysis of caged ATP initiates contractions with a short delay (10 ms or less). This result and those summarized above (2 and 3) suggest that the major portion of the delay between agonist-receptor interaction and contraction is due to activation of phospholipase C and InsP3 production, and about 0.2-0.5 s of the delay (22 degrees C) can be ascribed to prephosphorylation reactions between Ca2+, calmodulin, and myosin light chain kinase, and/or to mechanical processes, or to the chemical kinetics of two-step reactions. 5. Force development from rigor, initiated by photolysis of caged ATP in the presence of Ca2(+)-calmodulin, is rate-limited by myosin light chain phosphorylation; it is significantly accelerated if the myosin light chains are already phosphorylated prior to photolysis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2184780 TI - [Technics of bladder endosuturing]. AB - Urological surgery is rapidly developing towards less invasive and more conservative approaches without detriment to its proven efficacy. The authors, who perform endourologic surgery in 60% of the cases, have sought to enhance endoscopic suture techniques in the bladder using the triangulation procedure. Investigation was undertaken in experimental animals (large breed of female dogs) to assess various endosuture techniques and to develop the most appropriate instrument for this purpose. Following completion of the project's first phase, the authors claim that reconstructive endoscopic surgery of the bladder is already a reality and mechanical endoscopic suture of the bladder is forthcoming. PMID- 2184781 TI - [Perirenal hematoma caused by spontaneous upper calix rupture]. AB - We report a case of perirenal hematoma from spontaneous rupture of the upper urinary tract associated with parenchymal rupture due to a calculus lodged in the pelvic ureter. The clinical features were pain confined to the renal fossa, leukocytosis and Hct of 36%. Diagnosis was made by percutaneous punction pyelography. PMID- 2184782 TI - [Pyonephrosis as a cause of acute peritonitis. Review of the literature and report of a case]. AB - We report on a 52-year-old patient with spontaneous intraperitoneal rupture of pyonephrosis. The diagnostic features, preoperative findings and treatment are discussed and the literature reviewed. PMID- 2184783 TI - Vasoactive intestinal polypeptide (VIP)-like immunoreactivity in intraprostatic neurons and major pelvic ganglia in the rat. AB - VIP-like immunoreactive neurons have been found within the prostate and major pelvic ganglia of the male rats; they are of two different sizes. Moreover many VIP-like nerve fibers were found around the perikarya. On the basis of present data it is suggested that VIP-like prostatic nerves arise from both pelvic ganglia and intraprostatic neurons. PMID- 2184784 TI - Failure of chloroquine prophylaxis for falciparum malaria in pregnant women in Madang, Papua New Guinea. AB - Six hundred and twenty pregnant women, living under conditions of year-round transmission of malaria in a rural coastal area of Madang, Papua New Guinea (PNG), were followed while attending mobile antenatal clinics and receiving chloroquine prophylaxis (300 mg base weekly). Whole blood chloroquine concentrations measured by ELISA from samples collected at delivery indicated a high level of drug compliance in regular attenders. Susceptibility is increased in primigravidae to Plasmodium falciparum but not to other malaria species, with the peak prevalence occurring at nine to 16 weeks gestation. The incidence of P. falciparum infection per person-month was 20% for primigravidae, 25% for those gravida 2, 17% for those gravida 3 or greater, and 14% for non-pregnant nulliparae. Some 8.7% of primigravidae and 9.5% of those gravida 2 had persistent infections. Prophylactic chloroquine is required in this pregnant population because of altered host immunity during pregnancy, but is reduced in efficacy because of chloroquine resistance. Despite this, a missed clinic attendance resulted in a two-fold increase in incidence for all pregnant women, indicating that chloroquine was having some effect. PMID- 2184785 TI - Professor Thomas Wilson. PMID- 2184786 TI - Consequences of maternal anaemia on outcome of pregnancy in a malaria endemic area in Papua New Guinea. AB - The prevalence of anaemia during pregnancy was investigated in relation to parasite and spleen rates of pregnant women living in a defined study area in rural Madang, Papua New Guinea. The effects in pregnancy of anaemia, iron deficiency and malaria on the foetus were investigated. There is a high prevalence of anaemia in this population, with 44% of primigravidae and 29% of multigravidae having severe anaemia [haemoglobin (Hb) less than 8 g dl-1] after 28 weeks gestation. The odds ratio for severe anaemia at 0-16 weeks gestation in pregnant compared to non-pregnant women was 4.7 (P less than 0.0001). Forty-seven per cent of primigravidae and 32% of multigravidae had evidence of iron deficiency with high free erythrocyte protoporphyrin values (greater than 35 micrograms dl-1 whole blood) at antenatal booking. The risk of severe anaemia was significantly associated with splenomegaly and iron deficiency for all gravidae (splenomegaly P less than 0.05; iron deficiency, P less than 0.0002). Hb values at delivery were higher than at first attendance, with the greatest difference between groups malaria-positive at booking and malaria-negative at delivery (primigravidae 1.5 g dl-1, P less than 0.01; multigravidae, 0.7 g dl-1, P less than 0.01), indicating that malaria prophylaxis was an important factor in controlling anaemia. Two Hb groups were defined on the basis of the cut-off at 8 g dl-1, which corresponded to the lower quartile value at booking and delivery. A significantly increased risk of low birthweight was shown for primigravidae with values below 8 g dl-1 (65% v. 27%, P less than 0.025), but the prematurity rate was not significantly increased, indicating that the majority of babies were growth-retarded. Early pregnancy anaemia and iron deficiency were related to the risk of low birthweight in primigravidae. Current parasitaemia at delivery appeared a less important factor, although primigravidae with severe anaemia and parasitaemia at delivery had the lowest birthweights. The extent to which malaria control, using drug treatment and chemoprophylaxis, can reduce the risk of low birthweight will vary in relation to the prevalence and causes of anaemia in women. PMID- 2184787 TI - Eradication of bancroftian filariasis by diethylcarbamazine-medicated common salt on Little Kinmen (Liehyu district), Kinmen (Quemoy) Islands, Republic of China. AB - Since bancroftian filariasis constituted a major public health problem on Little Kinmen (Liehyu District), Kinmen (Quemoy) Islands, a control programme was conducted on this island from 1970 to 1982. A pre-control survey recorded a microfilarial rate (mfr) of 9.6%, a night blood microfilarial density (mfd) of 14.4/20 microliters blood, and a clinical rate of 26.2%. Culex quinquefasciatus was found to be the only vector of the parasitosis on the island, with an infection rate (Ir) with all filarial larval stages of 9.1% and a larval density (Ld) of 6.2. Diethylcarbamazine (DEC)-medicated salt (0.33% w/w) was administered to the whole population on Little Kinmen. Each person was estimated to take 12.7 g salt with 42 mg DEC daily for six months (July-December 1974). All accepted the programme, and no adverse side-effect was noted. During the control, the mfr and mfd were reduced to 0.3% and 1.9/20 microliters blood. The Ir and Ld were reduced to 0.8% and 1.3. Eight post-control surveys (1975-1982) revealed only two of 459 pre-control carriers positive and the remaining population of 7125 inhabitants negative. The two carriers were cured with a course of 5 g DEC. All family members of these carriers and their neighbours' families were given DEC-medicated salt for four months to clear the only remaining source of filarial transmission. In addition to a reduction in the prevalence of filariasis in humans and in mosquitoes to zero, the clinical manifestations disappeared in 52.4% of the pre control carriers and improved in 19.0%. There was no change in 19.8 and 8.7% had new manifestations. PMID- 2184788 TI - Infectivity of gametocytes of Plasmodium falciparum and Plasmodium vivax after storage in vitro. PMID- 2184789 TI - The Toledo Exercise and Diet Study. Results at 26 weeks. AB - This study was designed to test whether an exercise program is additive to diet counseling in lowering elevated blood cholesterol levels. From a screened population of 1024 subjects, we randomized 66 predominantly female subjects to two intervention groups: diet counseling and diet counseling with exercise. Subjects were selected who had elevated levels of serum low-density lipoprotein cholesterol, an average or low fitness level, and a diet high in saturated fat and cholesterol. After 26 weeks of intervention, 51 subjects exhibited significant decreases in serum levels of cholesterol, high-density lipoprotein cholesterol, triglycerides, and low-density lipoprotein cholesterol. The addition of exercise to diet counseling resulted in improved aerobic capacity, losses of body fat and weight, and further nonsignificant decreases in serum cholesterol and low-density lipoprotein cholesterol levels. Since these results differ from data acquired in individuals with normal to borderline serum cholesterol levels, further studies appear indicated in hypercholesterolemic subjects, especially in women. PMID- 2184790 TI - Depression in medical outpatients. Underrecognition and misdiagnosis. AB - Depression is a common problem in medical outpatients, yet primary care physicians recognize the disorder in only about half of their depressed patients. We compared physician recognition of depression (defined by chart notation or prescription of antidepressants) with diagnoses generated by the Diagnostic Interview Schedule (DIS) in 265 medical outpatients. Using DIS criteria, diagnoses of major depression in the past year or dysthymia (chronic minor depression) were made in 70 patients. Physicians recognized as depressed only 25 (35.7%) of the 70 DIS-depressed patients. However, 36 patients who were not depressed according to DIS were "recognized" as depressed by physicians. Patients misdiagnosed as depressed by physicians were older, less educated, had more outpatient visits, and were prescribed more medications. Receiver operating characteristic curves of two self-report depression scales suggest that these scales may assist physicians in recognizing depressed outpatients. We conclude that physicians underrecognize and misdiagnose depression in medical outpatients. PMID- 2184791 TI - Campylobacter (Helicobacter) pylori. Is peptic disease a bacterial infection? PMID- 2184792 TI - Calciphylaxis and systemic calcinosis. Collective review. AB - The phenomenon of calciphylaxis as defined by Selye is a condition of hypersensitivity that results in acute local calcification of various organs, with a whole host of morbid processes. Nephrocalcinosis and cutaneous calcifications have long been recognized in patients with chronic renal failure, but they have not often been reported in acute hyperparathyroidism or other causes of calcium-phosphate metabolism aberrations. The pathogenesis is not clear, and both the sensitizer and challenging agent in the hypersensitivity theory are often elusive, though hypercalcemia is the most consistent factor. The clinical features vary according to the organs affected and often mimic a gamut of more common conditions. Treatment is primarily supportive, with specific measures only possible when a sensitizer or challenger is identified. Correction of the hypercalcemia is, however, imperative. It is important to recognize this rare condition to avoid the more serious end results often reported. PMID- 2184793 TI - Nonsurgical management of cholelithiasis. AB - Cholecystectomy is accepted and effective therapy for symptomatic cholelithiasis; until recently, it was the only therapeutic option for patients with gallstones. Recently available alternative therapy for cholelithiasis includes oral dissolution therapy with the bile salts ursodeoxycholic acid and chenodeoxycholic acid, extracorporeal shock wave lithotripsy, and instillation of methyl tert butyl ether directly into the gallbladder. The role of each of these methods in the treatment of patients with gallstones will be reviewed, as well as the epidemiology, pathogenesis, natural history, and roentgenographic characteristics of gallstones, all of which are relevant when choosing appropriate therapy for the individual patient. PMID- 2184794 TI - Treatment of isolated systolic hypertension with labetalol in the elderly. AB - Antihypertensive therapy with labetalol was evaluated in a prospective, randomized, multicenter, double-blind study of 133 elderly patients with isolated systolic hypertension (standing systolic blood pressure [BP] greater than or equal to 160 mm Hg; diastolic BP less than 95 mm Hg). Following a placebo-washout period, patients received either labetalol (n = 70) or placebo (n = 63), which was titrated as necessary from 100 to 400 mg twice a day over a 6-week period. Once the BP was controlled (standing systolic BP less than 160 mm Hg, and greater than or equal to 10-mm Hg decrease from baseline) or the maximum dosage had been given, patients continued receiving the same regimen until the end of the titration period and throughout a 4-week maintenance period. Blood pressure was controlled in 57 (81%) of 70 of the labetalol-treated patients (86% receiving less than or equal to 200 mg twice a day) compared with 34 (54%) of 63 of the placebo-treated patients. Throughout the active treatment periods, BP was significantly lower in patients treated with labetalol compared with those taking placebo; mean standing systolic BP decreased 26 mm Hg in the labetalol group vs 9 mm Hg in the placebo group. Side effects were generally mild, and the dropout rates due to adverse experiences were similar between treatment groups (14% in the labetalol group vs 10% in the placebo group). In summary, labetalol can effectively lower systolic BP in the elderly without causing adverse orthostatic changes. PMID- 2184795 TI - Serotonin function and the mechanism of antidepressant action. Reversal of antidepressant-induced remission by rapid depletion of plasma tryptophan. AB - Brain serotonin content is dependent on plasma levels of the essential amino acid tryptophan. We investigated the behavioral effects of rapid tryptophan depletion in patients in antidepressant-induced remission. Twenty-one patients who were depressed by DSM-III-R criteria received a 24-hour, 160-mg/d, low-tryptophan diet followed the next morning by a 16-amino acid drink, in a double-blind, placebo controlled (acute tryptophan depletion and control testing), crossover fashion. Total and free tryptophan levels decreased 87% and 91%, respectively, during acute tryptophan depletion. Fourteen of the 21 remitted depressed patients receiving antidepressants experienced a depressive relapse after the tryptophan free amino acid drink, with gradual (24 to 48 hours) return to the remitted state on return to regular food intake. Control testing produced no significant behavioral effects. Free plasma tryptophan level was negatively correlated with depression score during acute tryptophan depletion. The therapeutic effects of some antidepressant drugs may be dependent on serotonin availability. PMID- 2184796 TI - Rapid cycling bipolar affective disorder. II. Treatment of refractory rapid cycling with high-dose levothyroxine: a preliminary study. AB - Eleven patients with rapid cycling bipolar affective disorder whose symptoms were refractory to their current medication regimen were entered into an open trial of high-dose levothyroxine sodium added to a stable regimen of those medications. At baseline, all patients exhibited a rapid cycling pattern and were evaluated prospectively through at least one affective episode. Levothyroxine was added to the baseline medication regimen, and the dosage was increased until clinical response occurred or until side effects precluded further increase. While patients were taking levothyroxine, scores on both depressive and manic symptom rating scales decreased significantly compared with baseline. This improvement was due to the clear-cut response of depressive symptoms in 10 of 11 patients, with manic symptoms responding in five of the seven patients who exhibited them during baseline evaluation. Four patients then underwent single- or double-blind placebo substitution; three patients relapsed into either depression or cycling. Treatment response did not depend on previous thyroid status. In 9 of 10 responsive patients, supranormal circulating levels of free thyroxine were necessary to induce clinical response. Side effects were minimal, and there were no signs or symptoms of levothyroxine-induced hypermetabolism. PMID- 2184797 TI - Adult outcomes of childhood and adolescent depression. I. Psychiatric status. AB - The present study was based on the clinical data summaries ("item sheets") of children who attended the Maudsley Hospital, London, England, during the late 1960s and early 1970s. These summaries were used to identify a group of 80 child and adolescent psychiatric patients with an operationally defined depressive syndrome. The depressed children were individually matched with 80 nondepressed psychiatric controls on demographic variables and nondepressive childhood symptoms by a computer algorithm. At follow-up, on average 18 years after the initial contact, information was obtained on the adult psychiatric status of 82% of the total sample. Adult assessments were made "blind" to case/control status. The depressed group was at an increased risk for affective disorder in adult life and had elevated risks of psychiatric hospitalization and psychiatric treatment. They were no more likely than the control group to have nondepressive adult psychiatric disorders. These findings suggested that there is substantial specificity in the continuity of affective disturbances between childhood and adult life. PMID- 2184798 TI - The mechanism of venous valve closure. Its relationship to the velocity of reverse flow. AB - Venous valves will close when the reversal of the normal pressure gradient generates a sufficient reverse flow velocity. By testing 20 healthy subjects with ultrasonic duplex scanning and controlled limb compression. It was found that the velocity of reflux is related to the external compression pressure. Valve closure is an abrupt cessation of reverse flow. In this study, with subjects in a supine position, valve closure was achieved only after reverse velocities exceeded 30 cm/s. This velocity was not generated by manual compression of the limb. With a Valsalva maneuver, this velocity is achieved only in the common femoral vein in 90% of the tested individuals. The reflux velocities in response to a Valsalva maneuver are progressively lower in more distal veins--the profunda femoris, the superficial femoral vein, and the popliteal vein. With reverse velocities lower than 30 cm/s, the valves will not close and reflux can persist. Valsalva's maneuver only allows a diagnosis of valvular competence at the most proximal level in the venous tree. PMID- 2184799 TI - The differential effect of corticosteroids on wound disruption strength in mice. AB - The detrimental role of corticosteroids on wound healing is well recognized. This study examined the effect of equipotent anti-inflammatory doses of dexamethasone sodium phosphate, methylprednisolone sodium succinate, or hydrocortisone sodium succinate on wound healing in mice. Mice were injected daily for 12 days; the mice were wounded on day 3 of steroid injection, with wound analysis done on day 10 after wounding. Dexamethasone and hydrocortisone significantly impaired wound healing, as assessed by wound disruption strength when compared with controls or methylprednisolone. Dexamethasone and hydrocortisone both displayed dose dependent relationships for impairment of healing, while over comparative doses, methylprednisolone failed to affect healing significantly. Regression analysis revealed nearly identical curves for hydrocortisone and dexamethasone that differed significantly from that of methylprednisolone. Our observations suggested that these preparations possessed a differential effect on the healing wound that should be considered to minimize postsurgical or traumatic wound healing problems. PMID- 2184800 TI - Lymphocytes. Window to the future. AB - The surgical sciences have made significant advances in our understanding of the immunological alterations associated with transplantation, trauma, oncology, and wound healing. Immune surveillance, regulation, and effector cell functions have been demonstrated to play integral roles in these disease states. Immune manipulation may be an effective therapeutic modality with even greater potential for the future. This study highlights recent progress in our understanding of immunomodulatory interventions that exploit manipulations in lymphocyte function in transplantation. PMID- 2184801 TI - The maintenance of weight loss after behavioral treatment. A review. AB - This article reviews the recent empirical literature on the behavioral treatment of obesity in an attempt to delineate those variables that are most closely related to the posttreatment maintenance of weight loss. Such variables were found to fall into three general categories: adherence to treatment and use of behavioral skills, posttreatment vigilance regarding both weight fluctuation and the skills learned in therapy, and intraindividual physical and emotional factors. An attempt is made to develop a rational understanding of these findings, which appear to be consistent with Kanfer's self-regulation model of self-control. Implications for treatment and future research are discussed. PMID- 2184802 TI - [Karl Heinrich Ulrichs. His life and work]. PMID- 2184803 TI - [The possible pathogenic factors of Actinomyces pyogenes. A review]. AB - Actinomyces pyogenes, an important pathogen of the bovine udder, was mainly characterized by production of the enzymes protease and neuraminidase. Both enzymes could be isolated and further analyzed. In addition A. pyogenes demonstrated lectin-like surface structures which caused hemagglutination reactions of neuraminidase treated erythrocytes. Further surface antigens of A. pyogenes which characteristically cross reacted with antisera against group polysaccharide antigens of streptococci of serological group G allowed an additional serological identification of this species. A. pyogenes further demonstrated binding properties for the plasma proteins alpha 2-macroglobulin, haptoglobin and fibrinogen and bacteriocin-like activities which caused growth inhibition of micrococci and staphylococci. PMID- 2184805 TI - The cholesterol facts. PMID- 2184804 TI - [Veterinary examinations of horses during purchase transactions]. AB - Veterinary examinations of horses on the occasion of sale or purchase take place on the basis of contracts for work and services. Three types may be distinguished: Examinations for sale (by order of the seller before the sales contract is concluded) Guarantee examination (by order of the buyer after conclusion of the sales contract) (Real) purchase examination (under a conditional contract of purchase). In the latter case the veterinarian acts as trustee for both seller and buyer and is equally obliged to both parties morally and at law. The deficiencies of the law of warranties for contracts of purchase of horses have led to the situation that more and more purchasers try to shift the risk to the veterinarian by ordering a comprehensive examination of the horse. In the light of several new court decisions the veterinarian bears a substantial risk of liability in those cases. The veterinarian is not only obliged to discover every irregularity in the health of the horse and to inform his customer accordingly; furthermore he has to inform his customer about the risks resulting from any irregularity he might have found. On the other hand the veterinarian is not obliged to make a binding prognosis of the future capabilities of the horse. The limitation period for claims of damages in case of inaccurate statements and opinions on the horse's health, which result from the veterinarian's negligence, is 30 years. The veterinarian can restrict his liability as to the limitation period and as to the maximum amount of liability. This can be done by employing standard form contracts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2184806 TI - In the shadow of the Baron: sudden death due to Munchausen syndrome. AB - The authors describe a woman who died suddenly in an emergency department restroom after self-injection of corn starch in an attempt to gain admission to the hospital. At autopsy, multiple pulmonary vascular corn starch granulomata were identified, as well as pulmonary arteries filled with brewer's yeast. Retrospective evaluation of the patient's medical history showed multiple signs of Munchausen Syndrome. The authors suggest that the case illustrates the importance of scene investigation and review of the medical history by emergency department personnel and the forensic pathologist. PMID- 2184807 TI - Trismus: modern pathophysiological correlates. PMID- 2184808 TI - Contact lens complications. AB - Contact lens wearers who develop complications related to their lens use are likely to present to emergency departments for care. The pathophysiology of contact lens complications is outlined, and clinical presentations of various conditions related to both soft and hard lens wear are summarized. Guidelines for emergency department management are suggested. PMID- 2184809 TI - The aging electrocardiogram. AB - With advancing age, widespread histologic changes in the conduction system occur. These changes may alter several features of the aging electrocardiogram, including duration of the PR and QT intervals, orientation of the electrical axis, duration and morphology of the atrial and ventricular complexes, and characteristics of the ventricular repolarization. And although ST segment and T wave abnormalities may be the only clue to acute ischemia, they are nonspecific and associated with a multitude of noncardiac causes. With an awareness of atypical presentations and difficulties in ECG interpretation, emergency physicians may be able to improve the assessment and triage of elderly patients with acute coronary ischemia. PMID- 2184810 TI - Environmental medicine: an annotated bibliography of the literature, 1987-1989. PMID- 2184811 TI - Effect of fluids on life span of peripheral arterial lines. AB - This study examines the effect of two different fluids to maintain peripheral arterial line patency at 1 to 2 ml/hr in a randomized controlled trial. Sixty sick newborn infants requiring ventilatory support and frequent blood gas monitoring were randomly assigned to receive either heparinized normal saline (HNS) or heparinized 5% dextrose water (HD5W) to maintain peripheral arterial line patency. One unit of heparin was added to each mililiter of both solutions. The duration of functional arterial lines, sodium balance, and number of peripheral punctures for blood glucose monitoring were compared using Student's t test for independent samples. HNS peripheral arterial catheters functioned significantly longer than HD5W without increased risk of hypernatremia. We conclude that HNS in arterial catheters is safe, lasts longer, and saves the infant (1500 gm or more) from the unnecessary stress of multiple peripheral punctures for blood glucose measurements, which can be obtained from the arterial catheter if glucose is not part of the infusate. PMID- 2184812 TI - Tuberous sclerosis in pregnancy. AB - Tuberous sclerosis is an autosomal dominant disorder of hamartoma formation in which manifestations may occur in skin, brain, and viscera. In the past, it was believed that the typical presentation included seizures, mental retardation, and facial angiofibromas ("adenoma sebaceum"). This disorder is now recognized to show wide variability of expression. There are only four cases of tuberous sclerosis in pregnancy in the literature. Two of these had favorable maternal and fetal outcomes and the remaining two presented with serious maternal and fetal complications. These included acute intra-abdominal bleeding due to a ruptured renal tumor, which led to renal failure requiring hemodialysis, and severe preeclampsia with pathologically enlarged kidneys noted at the time of cesarean section. This study presents two more cases of tuberous sclerosis in pregnancy. The first case had renal involvement with bleeding into a renal cyst, renal failure, preeclampsia, and severe intrauterine growth retardation. The second case was complicated by preterm premature rupture of the membranes and preterm labor. Renal involvement appears to be the single most important prognostic factor in pregnancies with tuberous sclerosis. Renal evaluation should be performed in any patient who presents for preconceptional counseling. PMID- 2184813 TI - Hyperlipidemic pancreatitis in pregnancy: a case report and review of the literature. AB - A case of pancreatitis associated with type I primary hyperlipoproteinemia in pregnancy is reported, with a review of the literature. There have been 11 cases of hyperlipidemic pancreatitis during pregnancy reported in the English literature since 1956. This case is the first report of adult respiratory distress syndrome complicating hyperlipidemic pancreatitis in pregnancy. Guidelines for prevention and management of this rare disorder are presented. PMID- 2184814 TI - Ultrasound determination of fetal abdominal circumference: a comparison of measurement methods. AB - The measurement of fetal abdominal circumference by the direct perimeter method using a digitizer was compared with calculation of this measurement using the fetal mean abdominal diameter in 235 cases. The directly measured abdominal circumference was found to be greater than the calculated value (p = 0.00014). The magnitude of the difference, however was only 1.3 +/- 2.2%, which is smaller than the average interobserver measurement error. Although statistically significant, the difference between these two measurement methods is not clinically significant, and these data and discussion show that either method is acceptable to determine fetal abdominal circumference. PMID- 2184815 TI - Imaging case of the month. Cerebral ventricular dilation and diaphragmatic elevation in congenital myotonic dystrophy. PMID- 2184816 TI - Stilbene and chalcone synthases: related enzymes with key functions in plant specific pathways. AB - Several years of extensive research using the new powerful techniques of molecular biology have enabled the direct comparison of functionally or evolutionarily related genes and their products at the nucleotide and amino acid sequence levels. Two types of synthase with similar functions are discussed as an interesting example. Stilbene synthases, e.g. resveratrol synthase, produce the stilbene backbone as a key reaction in the biosynthesis of stilbene-type phytoalexins. Chalcone synthase is a key enzyme in the biosynthesis of flavonoids, including certain phytoalexins derived from a 6'-deoxychalcone which is synthesized by cooperation of chalcone synthase with a reductase. Resveratrol and chalcone synthases utilize the same substrates (4-coumaroyl-CoA and 3 molecules of malonyl-CoA) and catalyze the same condensing type of enzyme reaction (resulting in sequential addition of acetate units via malonyl-CoA), but the products differ in the newly formed ring systems (resveratrol and naringenin chalcone). A comparative analysis of cloned DNA sequences and of the reaction mechanisms indicates that the two enzymes are closely related. It seems likely that the proteins possess a common scaffold for substrate recognition and for the condensing reaction, and that the different folding of an enzyme-bound intermediate prior to closure of the new aromatic ring is responsible for the formation of the different products. The same type of condensing reaction is utilized by the 2-ketoacyl-ACP synthases of fatty-acid biosynthesis. However, the available data indicate that these enzymes share little overall homology with either resveratrol or chalcone synthase. One exception may be a short amino acid sequence which corresponds to the active center of the condensing reaction in 2 ketoacyl-ACP synthases. PMID- 2184817 TI - Streptococcal toxic shock syndrome. PMID- 2184818 TI - Relationship between free amoeba and Legionella: studies in vitro and in vivo. AB - In 1980, Robowtham demonstrated that Legionella multiplies in free amoeba cytoplasm and hypothesized that the amoeba could act as a reservoir of virulent bacteria. In this paper we report various aspects of the relationship between amoeba and Legionella. A liquid medium co-culture method was applied to Acanthamoeba sp. and Legionella pneumophila serogroup 1. Within 4 days, Legionella growth increased by 2 log s CFU/ml. Using a direct immunofluorescence assay and electron microscopy, Legionella was shown to grow abundantly inside phagosomes, and bacteria and/or antigen were present on the cytoplasmic membrane of the amoeba. These aspects are very similar to those observed with Legionella infected alveolar macrophages. The morphology and structure of Legionella cells were modified after 20 days of co-culture: - viable bacteria showed large fatty cytoplasmic inclusions, - gas liquid chromatography analysis demonstrated a decrease in the i16:0 fatty acid ratio. Cystic forms of amoeba were abundant but none contained viable Legionella. In an in-vivo study using a guinea-pig aerosol infection model, we compared the virulence of Legionella in co-culture with Legionella grown on charcoal dialysed yeast extract (CDYE) agar medium. The Legionella obtained by co-culture had an LD 50 (50% lethal dose) similar to that obtained for those grown on CDYE, showing that bacterial virulence is preserved in the cellular model. PMID- 2184819 TI - Cross-reactive polysaccharide antigens (types a, d, and h) of the mutans group of streptococci: different molecular forms of the type as distinguishable by monoclonal antibodies. AB - As compared to the previous precipitin inhibition tests differences were found in the reactivities of monoclonal antibodies (MAbs), a-4 and a-84 with Streptococcus cricetus (serotype a) in an enzyme immunoassay using whole cells, purified cell wall antigen and haptenic sugars coated onto microtitre wells. Investigation into the differences led to the finding that the purified antigen from S. cricetus cells consisted mainly of three forms with different molecular weights and sugar contents. MAb a-4 reacted with a high molecular weight form (AgI, molecular weight of 46,000) and low molecular weight forms (AgII and AgIII, molecular weights of 9,800 and 20,000, respectively) whereas MAb a-84 reacted only with the high-molecular form. Gas chromatographic analysis revealed that all antigens contained rhamnose, galactose and glucose but in different ratios of the sugars. Although the binding site of AgII/AgIII with MAb a-4 seemed to be slightly different from that of AgI with MAb a-84, the predominant immunodeterminant of the antigens was considered to be the same. On the basis of these results, the chemical structures of the antigenic determinants are suggested. The nature of the antigen-antibody reactions is discussed. PMID- 2184820 TI - Evidence that coating of Mycobacterium leprae surface antigens reduces its ability to hinder host microbicidal functions. AB - Mycobacterium leprae extracted and purified from experimentally infected armadillo was coated with rabbit sera raised against the total antigens of the following species of mycobacteria: M. leprae, M. avium, M. bovis BCG, and M. fallax. In addition, the bacteria were also coated either with serum from a lepromatous (LL), or a tuberculoid (TT) leprosy patient. The effectiveness of surface coating was verified by electron microscopy, with the aid of gold immunolabelling. The coated bacilli were phagocytized by mice bone marrow-derived macrophages, and the phagosome-lysosome fusions (PLF) were assessed during phagocytosis using acid-phosphatase (AcPase) cytochemistry. As compared to control preparations (like-wise treated with non-immune serum), significant but partial reversion of PLF inhibition was observed in all cases except when bacteria had been incubated with M. fallax antiserum (rapidly growing, non pathogenic species). The results obtained suggest that some of the antimycobacterial antibodies may offer partial protection to the host during early events of infection by reverting the usual pattern of inhibition of PLF in infected macrophages. PMID- 2184821 TI - A single recessive non-MHC diabetogenic gene determines the development of insulitis in the presence of an MHC-linked diabetogenic gene in NOD mice. AB - To study the genetic control of insulitis in non-obese diabetic (NOD) mice, we performed breeding studies in crosses of NOD with non-diabetic strains, ICR-L line Ishibe (ILI), non-obese non-diabetic (NON) and C3H/He mice. The ILI mouse serologically shared the same MHC Class I and Class II as the NOD mouse. Insulitis was defined as islets invaded by lymphoid cells. Periductular, perivascular and peri-insular lymphoid cell infiltrations were often observed in NOD mice and appear to be the initial lesion leading to insulitis. Such lesions, however, were found in 1-year-old ICR, ILI, NON and Cataract Shionogi (CTS) mice of the NOD's sister strain. The lymphoid cells did not invade the islets in ICR, ILI, NON and CTS mice. The incidence of insulitis was 0% in F1 generations and 40% in female backcrosses (BC) [(ILI x NOD)F1 x NOD] at 9 weeks of age, 48 and 50% in BC[(NON x NOD)F1 x NOD] and BC[(C3H/He x NOD)F1 x NOD] at 1 year of age, respectively. Backcross animals were typed for the MHC to investigate correlation between the development of insulitis and MHC haplotypes. Among the backcross females with insulitis, approximately half the animals were heterozygous for MHC(non/nod) in BC[(NON x NOD)F1 x NOD] and MHC(k/nod) in BC[(C3H x NOD)F1 x NOD]. Among the backcross females with no insulitis, approximately half the animals were homozygous for MHC(nod/nod) in BC[(NON x NOD)F1 x NOD] and in BC[(C3H x NOD)F1 x NOD]. The results suggest that a single recessive non-MHC diabetogenic gene determines the development of insulitis regardless of NOD MHC homozygosity or heterozygosity. PMID- 2184822 TI - Energy metabolism reactions in ruminant muscle: responses to age, nutrition and hormonal status. AB - Energy expenditure in muscle comprises reactions related to intermediary metabolism and those of posture and activity. The metabolic reactions respond to a wide range of nutritional and hormonal stimuli and are often apparently co ordinated; in magnitude, however, their contribution to energy requirements can be minor compared with locomotion and posture. Metabolic reactions include protein turnover, ion transport and substrate cycles. In young ruminants muscle protein synthesis responds to intake but effects on energy expenditure are less pronounced; the situation with the adult is unclear. The involvement of insulin in ruminants may differ from that in monogastrics but effects are observed with thyroid hormones. Ruminant muscle may have a higher energy requirement for Na+, K+ transport which responds in proportion to total oxygen uptake to alterations in intake. Thyroid hormone treatment and, probably, the catecholamines enhance both Na+, K+ and Ca2+ transport. Muscle has fewer substrate cycles than liver and each may contribute only 1-3% toward oxygen consumption. Several are sensitive to insulin, but larger responses are observed with thyroxine and epinephrine and under stress conditions, therefore, may account for significant proportions of heat increment. Energy costs of standing may be considerable and posture movements may change with diet quality and quantity. Locomotory activity may mask changes in the contribution of metabolic reactions in response to different stimuli. Approximately 80% of energy costs for muscle in vivo are accounted for by protein turnover (20-25%), ion transport (25-30%), substrate cycling (5-8%) and standing (30%). Better integration of experiments in vivo and in vitro is required to improve the quantification and resolve data anomalies. PMID- 2184823 TI - Energy metabolism in the digestive tract and liver of cattle: influence of physiological state and nutrition. AB - Major functions of portal-drained viscera (PDV) and liver of cattle include absorption of digestion products and modification of the body's supply of intermediary metabolites. The disproportionately high metabolic rate of PDV and liver (7-13% of body tissues) is exemplified by their oxygen uptake (40-50% of whole body). Extensive metabolism of glucose, volatile fatty acids and amino acids by PDV modulates nutrient supply from the diet such that most responses to diet or physiological state are a function of level of diet intake. Similarly, blood flow through PDV is highly correlated with energy intake across a range of body weight, physiological state or diet composition. Most common dietary responses in metabolite uptake by PDV are changes in uptake of ammonia and volatile fatty acids, which emphasize the strong energy: nitrogen interrelationship in the rumen and subsequently the rest of the body. The liver (tissue in series with PDV) removes glucose precursors and ammonia from its blood supply as part of its functions in gluconeogenesis, ammonia detoxification and urea synthesis. The liver also alters amounts and proportions of amino acids supplied by PDV. Accountable percentages of metabolizable energy from net PDV supply include: organic acids, 41-59%; amino acids, 5-13%; and heat energy (from oxygen uptake), 11-22%. PMID- 2184824 TI - [Pancreatic enzyme substitution in patients with mucoviscidosis]. AB - In CF-patients physical development is an important prognostic factor. Therefore, maldigestion in consequence of an exocrine pancreatic insufficiency must be payed special attention to. Only the acid-protected microsphere pancreatin preparations should be used for enzyme substitution. In estimating of effectiveness both subjective (pains, tolerance) and particularly objective parameters (balance investigations, stool-weight and -frequency, physical development) should be considered. Referring to this the determination of fecal chymotrypsin concentration is unsuitable. There are further possibilities for increasing the enzyme efficiency, which could soon become applicable. PMID- 2184825 TI - [Ultrasound-controlled cutting biopsy for collecting histologic specimens]. AB - The fine-needle puncture under ultrasound guidance has the disadvantage that the material obtained can only be evaluated by cytology. The cutting biopsy cannula represents a compromise between the fine and the Menghini needle. In this way, small tissue cylinders can be attained. The aim of the present study was to investigate to what extent the sampled specimen could be assessed by cytology or histology. Fine-needle puncture resulted in 22 (69%) out of 32 cases in material suitable for cytology. Cutting biopsy led in 34 out of 36 cases (94%) to specimen valid for histology. Thus, cutting biopsy clearly extends our diagnostic tools. It is not yet clear at present whether procedures with a higher risk - such as the Menghini puncture - can be in part replaced by alternative ones. PMID- 2184826 TI - [Patient management and research at the Central Scientific Research Institute for Gastroenterology in Moscow]. AB - This is an overview about the work of the Central Scientific Research Institute of Gastroenterology, Moscow, with special attention of hepatology. The speak goes about Delta hepatitis in Soviet Union, results of hepatoprotective treatment in experimental animals and in patients, and others. PMID- 2184827 TI - Chlorophylls in foods. PMID- 2184828 TI - Delayed light emission as a means of quality evaluation of fruits and vegetables. AB - DLE is probably produced by all fruits, vegetables, and plant materials undergoing photosynthesis. However, the intensity and duration of the emitted light vary widely depending upon many factors. Because of the strong dependence of DLE on the chlorophyll content, variation in the DLE can be expected among different varieties of the same product. Therefore, quality evaluation based on DLE measurements require careful selection of measuring criteria such as duration and intensity of illumination, dark period, and temperature. It is necessary to obtain precise values of DLE for a particular product under a set condition; and the measurement conditions should be carefully validated to establish a standard measuring criteria. In general, the quality evaluation of fruits and vegetables is based on three major aspects: maturity and/or ripeness evaluation, composition analysis, and internal and external defect detection. DLE measurements so far have focused mainly on maturity evaluation because of the definite relationship between the emitted light and chlorophyll concentration, which changes with maturity. It should be noted that chlorophyll alone is not sufficient; it is the complex of in situ chlorophyll and related compounds in plant materials that jointly contribute to the DLE. Composition of fruits such as sugar content has been related to DLE. Recently, DLE measurements have been applied to detect certain physiological stress responses and defects such as chilling injuries. However, these areas of research have not yet been fully explored. Further investigation relating to compositional quality and internal and external defects of fruits and vegetables with DLE measurement may offer solutions to certain complex quality evaluation problems. The duration of DLE after excitation involves a matter of at least several seconds. From a mechanical standpoint, this extended period of light emission offers a convenient time in which to separate excitation and measurement. However, the exponential decay necessitates very precise control of time between illumination and measurement. The broad activation spectrum permits wide choice and simple design of excitation sources. However, size, shape, and varietal variations of plant materials make uniform DLE measurements difficult. It is suggested that DLE measuring instruments be designed to make several measurements over the entire surface of the specimen. An average of such measurements would reduce the effect of surface nature and shape of the product. Reporting the DLE intensity per unit surface area of the product will eliminate the dependence of area of excitation on DLE.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2184829 TI - Chemical and nutritional changes in foods during extrusion. PMID- 2184830 TI - Effects of magnesium on skeletal metabolism. AB - Magnesium (Mg) makes up 0.5-1% of bone ash and is therefore not a trace element in the skeleton. Mg influences both mineral and matrix metabolism in bone by a combination of effects on hormones and other factors that regulate skeletal and mineral metabolism, and by direct effects on bone itself. The skeletal content of Mg is very variable both between and within species, and reported values range between 150 and 440 mmol/kg ash weight (AW). Dietary Mg has a direct influence and age an inverse influence on skeletal Mg content. It is unclear whether skeletal Mg content varies from region to region. In humans, reported values cluster around the 200 mmol/kg AW level, 30-40% lower than most rat data. Human iliac crest cortical bone has 10-20% less Mg per unit weight than iliac crest trabecular bone. Mg depletion adversely affects all phases of skeletal metabolism. In the rat, cessation of bone growth is noted with a decrease in both osteoblast and osteoblast activity, decreased bone formation, osteopenia, increased fragility and development of a form of 'aplastic bone disease'. The epiphyseal growth plate is thinned and the percent ash weight of the growth plate is increased, possibly due to enhanced crystallization of bone salt under conditions of Mg depletion. In contrast, in chicks and in rats with severe Mg deficiency, these 'antianabolic' effects are not observed but instead, predominant inhibition of bone resorption occurs with increased cortical thickness rather than osteopenia, and the occasional development of subperiosteal hyperplasia or of fibrous tumors of the periosteum. It is probable that this unusual response under conditions of severe Mg deficiency is in part an indirect effect secondary to a defect in secretion and/or skeletal responsiveness to parathyroid hormone (PTH) and vitamin D metabolites. Mg excess also has adverse biologic effects on bone. Crystallization of bone salt is severely impaired and an osteomalacia-like picture may be produced with decreased osteoblastic activity, widened growth plates, excessive osteoid seams and short, thickened bones. In some studies, especially in mice, Mg excess stimulates bone resorption, independently of PTH. The role of Mg deficiency and excess in human skeletal conditions requires more extensive investigation. Bone Mg is uniformly increased in renal insufficiency and may play a role in renal osteodystrophy since improvement has been noted in the osteomalacic component by normalizing the serum Mg. Decreased bone Mg has been reported in alcoholic patients, diabetes and in osteoporosis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2184832 TI - Serotonin, dopamine and GABA involvement in alcohol drinking of selectively bred rats. AB - Neurochemical and neuropharmacological studies were undertaken to assess the involvement of CNS serotonin (5-HT), dopamine (DA) and GABA systems in regulating the alcohol-drinking behavior of two lines of rats selectively bred for their high alcohol-seeking behavior, namely the alcohol-preferring P line and the high alcohol-drinking HAD line of rats. Neurochemical data indicate that high alcohol seeking behavior (when compared with data from rats with low alcohol-seeking characteristics) is associated with: a) lower (10-20%; p less than 0.05) contents of 5-HT in certain limbic regions (e.g., nucleus accumbens, frontal cortex, hypothalamus and hippocampus); b) a lower (10-15%; p less than 0.05) content of DA in the nucleus accumbens; c) higher (20-35%; p less than 0.05) densities of 5 HT1A binding sites in some limbic regions (e.g., medial nucleus accumbens, medial prefrontal cortex and ventral hippocampus); and d) a greater (20-50%) density of GABA axon terminals in the nucleus accumbens. Furthermore, the acute administration of high doses of ethanol appears to increase the activity of the 5 HT and DA projections to the nucleus accumbens of the P line of rats (as indicated by the 20-30% elevated tissue levels of 5-HT and DA metabolites following IP ethanol administration); neuronal tolerance to alcohol appears to develop in both these monoamine pathways, as suggested by an attenuated effect on metabolite levels by a challenge dose of ethanol given to P rats that had been chronically drinking alcohol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2184831 TI - Oral ethanol self-administration: a behavioral pharmacological approach to CNS control mechanisms. AB - Using rats which are self-administering ethanol in an operant situation, we have tested a variety of agonists and antagonists in an attempt to determine the role various CNS neurotransmitters may play in ethanol drinking. The major emphasis of the work has been on the dopaminergic and the benzodiazepinergic systems. This paper reviews prior work and provides new data on additional agonists and antagonists. The data suggest a possible reciprocal interaction between dopamine and benzodiazepine brain systems. This hypothesis is based on the change in pattern of lever responding which results when various agonists, antagonists and inverse agonists related to these neurotransmitters are compared. That is, similar changes in response pattern are found for dopamine agonists and benzodiazepine inverse agonists. On the other hand, dopamine antagonists and benzodiazepine agonists are similar to each other and produce a different set of changes. A neural circuit for a reciprocal interaction between the ventral tegmentum and the nucleus accumbens is proposed as one possible pathway which may be involved in these observations. PMID- 2184833 TI - Genetic approaches to studying drug abuse: correlates of drug self administration. AB - Some important issues in substance abuse are the relationship between propensity to self-administer a drug and neurosensitivity to that drug; similarities and differences between various models of drug-seeking behavior; and the commonality of drug-seeking behavior across drugs and genotypes. Findings related to these issues are now emerging from the areas of pharmacogenetics and operant drug self administration. Ethanol has been readily established as a positive reinforcer in AA (Alcohol Accepting), P (Preferring) and LEWIS rats, as well as C57BL/6J and LS/Ibg mice. In low ethanol preferring F344 and NP (Non-Preferring) rats, ethanol maintains significant but low levels of responding. Ethanol does not maintain lever-pressing behavior in BALB/cJ or SS/Ibg mice, and is avoided in DBA/2J mice. This pattern of reinforcement from ethanol is only moderately correlated with ethanol preference, and is not correlated with neurosensitivity to ethanol, at least as measured by duration of loss of the righting reflex (LORR). However, these genotypic patterns of reinforcement from ethanol do appear to correlate highly with patterns of reinforcement from cocaine and opiates. From these findings it is concluded that: 1) there exist important genetic determinants of drug reinforced behavior; 2) ethanol preference is not a highly accurate measure of reinforcement from ethanol; 3) sensitivity to ethanol as measured by LORR and self-administration of this drug are not highly genetically correlated; and 4) drug-seeking behaviors maintained by ethanol, cocaine and opiates may have at least some common biological determinants. PMID- 2184834 TI - Neurobehavioral studies of ethanol reward and activation. AB - Although generally considered to be a depressant drug, ethanol has both stimulant and depressant effects on behavior. This biphasic action of ethanol may be related to its reinforcing effects and to the neurobehavioral events that occur with changes in blood alcohol concentration (BAC). Ethanol was found to reduce the threshold and increase response rates for brain stimulation reward (BSR) at lateral hypothalamic, but not ventral noradrenergic bundle brain sites. These effects were also found to only occur when testing occurred on the ascending limb of the BAC. Studies of the effects of ethanol on open-field activity showed that the stimulant effects of low doses of ethanol were also seen only during the ascending limb of the BAC; depression was usually found during the descending limb. Neurochemical data from other investigators suggest that the facilitation of BSR and stimulation of activity may be mediated by mesolimbic dopamine systems. PMID- 2184835 TI - Oral self-administration of ethanol and not experimenter-administered ethanol facilitates rewarding electrical brain stimulation. AB - The effects of ethanol on brain-stimulation reward (BSR) were investigated in rats orally self-administering ethanol. Electrodes were stereotaxically implanted in the medial forebrain bundle (MFB) of male F-344 rats. A rate free threshold procedure was used. Animals demonstrated significant threshold-lowering effects after considerable ethanol self-administration experience. To elucidate the significance of the contingent nature of the route of administration in the threshold-lowering effects of ethanol on BSR, a comparison of animals self administering ethanol to yoked animals receiving it passively through a gastric cannula was made. Significant threshold-lowering effects were only found in the animals self-administering ethanol and not those receiving it noncontingently. Thus, to the extent that brain-stimulation reward is a model of drug-induced euphoria, these results suggest that the reinforcing effects of ethanol are dependent to a greater degree on an interaction between experimental, environmental and pharmacological factors, than other abused drugs. PMID- 2184836 TI - Genetic components of ethanol responses. AB - A powerful technique for determining the role of a particular neurotransmitter in mediating a response to ethanol (EtOH) is the analysis of selectively bred lines of animals. Lines selected for sensitivity and resistance to an EtOH effect differ principally in gene frequencies for genes affecting the selected response. Hence, other differences between the lines are likely due to pleiotropic actions of those genes. We discuss behavioral pharmacological experiments in two sets of selected lines. Withdrawal Seizure-Prone (WSP) and -Resistant (WSR) mouse lines were selected for severe and minimal handling-induced convulsions (HIC), respectively, after withdrawal from chronic EtOH inhalation. The HIC is also elevated after acute administration of low doses of convulsant drugs. WSP mice were found to be more sensitive than WSR mice to many such drugs. There was no apparent specificity of such effects to any particular neurotransmitter system. Thus, genetic determination of a behavioral response to EtOH in this case cannot be traced to the influence of a single neurotransmitter system. COLD and HOT mice were selectively bred to show severe and mild hypothermia, respectively, after acute EtOH administration. COLD mice are also more sensitive to a number of other alcohols, barbiturates, and other general central nervous system depressants. When tested for sensitivity to a number of drugs with specific effects on neurotransmitter systems, COLD and HOT mice did not differ in sensitivity to drugs affecting dopaminergic, alpha-adrenergic, or nicotinic acetylcholinergic systems. COLD mice were more sensitive, however, to opioid and serotonergic drugs. Thus, analysis of these selected lines was successful in identifying particular neurotransmitters which may be important in EtOH-induced hypothermia. PMID- 2184837 TI - Specific removal of endotoxin from protein solutions by immobilized histidine. AB - A method for reducing endotoxin contamination in various solutions by immobilized histidine is described. Immobilized histidine is a porous adsorbent suitable for the adsorption of endotoxin with a high affinity over a wide range of pH and temperature and at low ionic strength (gamma/2 less than or equal to 0.1). When a purified endotoxin originating from Escherichia coli UKT-B was studied, the apparent dissociation constant between endotoxin and the adsorbent was 7.3 X 10( 13) M. The adsorbent was able to remove various kinds of endotoxin originating from gram-negative bacteria; the concentration of endotoxin was reduced from 1000 to less than 0.01 ng/ml in water. It is shown that the adsorbent specifically adsorbs endotoxin provided that the adsorption conditions are properly selected. Some examples of the specific removal of endotoxin from high-molecular-weight physiologically active substances such as tumor necrosis factor and lysozyme are shown. PMID- 2184838 TI - Substrate specificity and inhibitor structure-activity relationships of recombinant human renin: implications in the in vivo evaluation of renin inhibitors. AB - Homogeneous, active recombinant human renin obtained from Chinese hamster ovary (CHO) cells was characterized in vitro by (i) determination of its relative rates of hydrolysis of plasma angiotensinogens (ANGs) from human, monkey, baboon, rat, pig, rabbit, hamster, and dog and (ii) analysis of several synthetic ANG-based, inhibitors ranging in IC50 from 10(-10) to 10(-6) M. Comparison of the recombinant human renin with human kidney renin showed that these enzymes were indistinguishable from each other in terms of their plasma ANG specificities and inhibition by synthetic renin inhibitors. Porcine kidney renin was also characterized and shown to display plasma ANG hydrolysis profiles and inhibitor potencies that were markedly different from those of human renins. Finally, the results using the above plasma ANGs extend previous studies showing that the substrate specificity of human renin may be influenced by the amino acid residues at P2 (i.e., Ile, Val, or Tyr) and P3 (i.e., His or Tyr) sites. The relevance of these data to in vivo evaluation of renin inhibitors in animal models is discussed. PMID- 2184839 TI - Towards large-scale purification of natural CSF-1 from human placenta tissue extracts. AB - The monocyte-macrophage colony-stimulating factor (colony-stimulating factor 1) is characterized and partially purified from industrially processed human tissues for the first time. A five-step purification procedure using placenta tissue extracts furnished a 13,620-fold enrichment of biological activity. This procedure includes a "pilot" scale anion-exchange chromatography at pH 4.5, gel permeation, and lectin affinity separation followed by HPLC steps (hydrophobic interaction and C18 reverse-phase chromatographies). The purified bioactive material, which stimulates only monocyte-macrophage progenitors and mature cells, showed an Mr of 58,000-62,000 (gel filtration) and an isoelectric point of 3.8 4.0. The hydrophobicity of the molecule was low, and the biological activity was eluted at 50% acetonitrile on a C18 reverse-phase HPLC column. It was totally inactivated by 2-beta-mercaptoethanol reduction and heat treatment. Immunoprecipitation and neutralization of biological activity with specific anti CSF-1 antibodies (not shown) demonstrated that this material was CSF-1. Step 5 of this protocol yielded two silver-stained bands on 12.5% SDS-PAGE: a major 55-kDa band (96%) and a minor 33-kDa band (4%). CSF-1 was detected exclusively in a band of 52-62 kDa by both Western immunoblotting and bioassays. Immunoaffinity techniques using antibodies directed against selective epitopes on the placental CSF-1 are now considered to purify this material to homogeneity. This approach to the mass production of natural CSF-1 from human tissue has advantages with respect to both the difficulty of post-translational processing of bioactive material in procaryotes and the cost of eucaryotic cell cultures. PMID- 2184840 TI - Preparation of active hybrid enzymes composed of the native and chemically inactivated aspartase subunits from Escherichia coli. AB - The hybridization of the native and chemically inactivated aspartase from Escherichia coli was studied. Preparations of the tetrameric enzyme obtained by mixing the native and N-ethylmaleimide (NEM)-inactivated aspartase in 4 M guanidine-HCl followed by 51-fold dilution at room temperature retained catalytic activity. Affinity chromatography on AF-Red TOYO-PEARL separated several active components in the hybridized preparations, and the presence of [14C]NEM inactivated subunits in the active hybrids was demonstrated. The addition of the native aspartase to Sepharose-bound NEM-inactivated enzyme in 4 M guanidine-HCl resulted in the formation of an immobilized enzyme with enzyme activity. The specific activity of the various hybrids, composed of unmodified and [14C]NEM inactivated subunits, was roughly proportional to the number of unmodified subunits in each tetramer. Furthermore, when reversible denaturation was conducted on mixtures of the native and NEM-inactivated enzyme at various proportions, the enzyme activity recovered was proportional to the amount of the native enzyme added. These results strongly suggest that each subunit makes an independent contribution to the overall enzyme activity regardless of the presence of other subunits in the same molecule. The theoretical and practical implications of this work are discussed. PMID- 2184841 TI - Hexavalent chrome: threshold concept for carcinogenicity. AB - Certain hexavalent chromium (Cr6+) compounds when administered via inhalation at high doses have the potential to induce lung tumors in humans and experimental animals. Trivalent chromium (Cr3+) is an essential human and animal nutrient at levels of 50 to 200 micrograms/day. Recent data have shown that the human body is able to reduce Cr6+ to Cr3+. This reduction occurs in bodily fluids such as gastric juice, epithelial lining fluid of the respiratory tract, blood, and other fluids. Secondary reduction occurs at the cellular level by the cytosol, mitochondria, and microsomes. Thus, at low levels of exposure hexavalent chromium ions are reduced before the 6+ ions can interact with DNA unless the dose is sufficient to overwhelm the body's reduction capacity. This paper summarizes the available data concerning the reducing ability of the body and formulates the steps in the mechanism of cancer induction. These steps include: (1) only certain Cr6+ compounds have the capacity to interact with cellular components; (2) Cr6+ is reduced by body fluids and excess Cr6+ enters the cell (Cr3+ is poorly absorbed across membranes); (3) cellular organelles and the cytoplasm reduce Cr6+ to Cr3+; (4) excess Cr6+ can enter the nucleus; (5) Cr6+ reduction through 5+ and 4+ to 3+ has a potential to interact with the DNA molecule; and (6) if unrepaired, this DNA damage can lead to cancer induction. On the basis of current evidence Cr6+ has a threshold for carcinogenic potential in humans that is greater than the current TLV. PMID- 2184842 TI - Robin Hood is dead: the plight of hospital financing 1990. PMID- 2184843 TI - Enhancement of sexual function and fertility in spinal cord-injured males. AB - Trauma to the spinal cord in males may result in both erectile dysfunction and infertility. Reflex erections may be preserved in upper motor neuron lesions and psychogenic erections in lower motor neuron or incomplete lesions. There are numerous reports of abnormalities of testicular biopsies that may relate to increased scrotal temperature and other factors. Techniques to restore erections include intracavernous injections of vasoactive substances, vacuum tumescence constriction therapy and penile prostheses. All have potential adverse affects. When reflex function in the sacral cord is present, fertility can be improved by vibratory ejaculation. Subcutaneous physostigmine or electroejaculation may benefit individuals with intact fibers from the sympathetic outflow. This paper reviews sexual dysfunction in spinal cord-injured males with a focus on management techniques. PMID- 2184844 TI - Enzyme immunosensors based on electropolymerized polytyramine modified electrodes. AB - Highly sensitive amperometric enzyme immunosensors for human immunoglobulin G (IgG) were prepared on the basis of electrogenerated polytyramine (PTy, tyramine = p-(2-aminoethyl)-phenol) modified electrodes. Properties of PTy films changed depending on electrolysis conditions. On the basis of the found properties of the films, an effective IgG sensor was prepared: a PTy film was formed first from an acid solution on a Pt electrode, and the surface was further covered with a PTy film from an alkaline methanol solution to give a PTy doubly coated electrode on which anti-IgG was then immobilized. This electrode provided a large surface area with little non-specific adsorption of proteins. By means of the competitive enzyme immunoassay technique using glucose oxidase (GOD) labeled IgG conjugates, IgG was determined in the concentration range of c. 10 pg/ml-1 mg/ml from the oxidation current of H2O2 generated by the enzyme (GOD) reaction using the above IgG sensor. Also, an anti-IgG immobilized electrode, prepared by using a Pt electrode singly covered with a PTy film from an alkaline methanol solution, acted as an effective IgG sensor with a detection limit for IgG of c. 100 pg/ml. PMID- 2184845 TI - Intestinal cholesterol metabolism. AB - The handling of cholesterol by the intestine involves a balance between absorption, excretion and metabolism by gut microflora. Between 34-57% of dietary cholesterol is absorbed from the human intestine. Variables effecting the efficiency of cholesterol absorption include the absolute amount of cholesterol consumed, the presence of plant sterols, the fiber content of the diet, transit time and possibly the relative proportions of fatty acids in the diet. On average, 150 mg/day of cholesterol is excreted in the feces. Fecal cholesterol derives from biliary secretions into the intestine, sloughing of epithelial cells and unabsorbed dietary cholesterol. The major metabolic products of cholesterol in the gut are coprostanol, coprostanone, cholestanol, cholestanone and epicoprostanol. Bacterial metabolism of cholesterol can be influenced by diet as evidenced by significant variations among different population groups with different dietary habits. Altered patterns of intestinal bacterial metabolism of cholesterol may place persons at a higher risk of developing colonic disorders. Dairy products have been reported to influence the bacterial metabolism of cholesterol and possibly plasma cholesterol levels although the significance of these findings to overall cholesterol balance needs to be further defined. PMID- 2184846 TI - Lipid metabolism in bile acid malabsorption. AB - Malabsorption of bile acid increases cholesterol synthesis and activates hepatic LDL receptors which leads to enhanced elimination of cholesterol from the body. Interruption of enterohepatic circulation of bile acids may lead to a smaller bile acid pool, which, in turn, impairs cholesterol and fat absorption by reduced micellar solubilization. Together with reduced cholesterol absorption, the increased cholesterol loss as bile acids also reduces plasma cholesterol concentrations and the biliary cholesterol excretion, too. Diminished biliary cholesterol in bile acid malabsorption may contribute to the increased incidence of gallstones associated with ileal dysfunction. Malabsorption of bile acid leads to a fall in LDL-cholesterol concentration, and an increase of HDL-cholesterol concentration has been reported. VLDL-triglyceride concentrations are almost invariably raised. Enhanced cholesterol and bile acid synthesis in ileal dysfunction is reflected by raised concentrations of plasma cholesterol precursors, especially lathosterols, which can be used as an indicator of increased bile acid loss to faeces. Cholesterol absorption, in turn, correlates positively with plasma plant sterol concentrations levels and the ratio of lathosterols to campesterols can be used as a screening measurement for ileal dysfunction. Plasma fatty acid composition is also altered as a response to fat malabsorption associated with ileal dysfunction. The proportion of essential fatty acids is inversely correlated with faecal fat excretion and endogenous fatty acid synthesis is activated. PMID- 2184847 TI - Prevention of travellers' diarrhoea by Lactobacillus GG. AB - A placebo-controlled double-blind study was conducted on the efficacy of Lactobacillus GG in preventing travellers' diarrhoea. Altogether 820 persons travelling on holiday to southern Turkey to two destinations were randomized into two groups receiving either Lactobacillus GG or placebo in identical sachets. On the return flight each participant completed a questionnaire indicating the incidence of diarrhoea and related symptoms during the trip. Of the original group 756 (92%) subjects completed the study acceptably. The overall incidence of diarrhoea was 43.8% (331 cases). The total incidence of diarrhoea in the placebo group was 46.5% and in the Lactobacillus GG 41.0% indicating an overall protection of 11.8%. Protection rates varied between two different destinations with the maximum protection rate reported as 39.5%. Among older age groups there was significantly less diarrhoea when compared to younger travellers. Lactobacillus GG appeared to be effective in reducing the occurrence of travellers' diarrhoea in one of the two destinations with no side effects. PMID- 2184848 TI - Effect of Lactobacillus GG yoghurt in prevention of antibiotic associated diarrhoea. AB - The efficacy of Lactobacillus GG yoghurt in preventing erythromycin associated diarrhoea was studied. Sixteen healthy volunteers were given erythromycin acistrate 400 mg t.i.d for a week. The volunteers were randomly assigned into two groups taking twice daily 125 ml of either Lactobacillus GG fermented yoghurt or pasteurized regular yoghurt as placebo during the drug treatment. Subjects receiving Lactobacillus GG yoghurt with erythromycin had less diarrhoea than those taking pasteurized yoghurt. Other side effects of erythromycin, such as abdominal distress, stomach pain and flatulence, were less common in the GG yoghurt group than in the placebo yoghurt group. The subjects receiving Lactobacillus GG yoghurt were colonized with these bacteria even during erythromycin treatment as measured by faecal counts of total Lactobacillus GG. No Lactobacillus GG was found in the faecal samples of volunteers in the group taking pasteurized yoghurt. PMID- 2184849 TI - The influence of the normal flora on Clostridium difficile colonisation of the gut. AB - The normal stable flora of the gut of man and other adult animal species provides an effective barrier to infection by Clostridium difficile. Attempts to understand this mechanism have involved continuous flow and batch culture systems and colonisation of antibiotic pre-treated or germ free animals with gut flora from the same or unrelated species. In general attempts to re-create the barrier effect with the whole caecal or faecal flora have been successful both in vitro and in vivo, whereas attempts using components of that flora have not. The most recent developments in these types of studies have been studies aimed at understanding the mechanisms involved. Preliminary findings imply competition for various monosaccharides, especially those released from mucin, may be important. PMID- 2184850 TI - Generation of clonal DNA templates for in vitro transcription without plasmid purification. AB - WE present a rapid procedure based on the polymerase chain reaction for generation of double-stranded DNA templates suitable for in vitro transcription by T3 or T7 RNA polymerase. DNA fragments cloned into a phage promoter vector are amplified together with a flanking promoter to provide functional templates. Extension of oligonucleotide primer molecules harboring an RNA polymerase promoter sequence at their 5'-end allows positioning of the transcription start site within the insert. The procedure generates large amounts of linear transcription template without need to isolate and purify plasmid DNA from bacterial cells. PMID- 2184851 TI - A modification of the Omniblot Processing System allowing its use in western blotting. PMID- 2184852 TI - An improvement of a rapid method using Qiagen columns to purify plasmids. PMID- 2184853 TI - A reversible multi-well chamber for incubation of cultured cells with small volumes: application to screening of hybridoma fusions using immunofluorescence microscopy. AB - Immunofluorescence microscopy is a powerful technique for detecting the location of surface and intracellular antigens in individual cells. However, using standard methods, processing large numbers of samples for immunofluorescence is cumbersome and difficult. To simplify greatly this process, we have developed a chamber that reversibly creates multiple small wells in a large (150 mm) tissue culture dish. This device allows the rapid and convenient processing of hundreds of samples each of 100 microliters volume. Each sample is examined using a short working distance, high numerical aperture immersion objective for maximum sensitivity and resolution. This apparatus makes immunofluorescence a practical method for the primary screening of hybridoma clones. PMID- 2184854 TI - Antigens on rat spermatozoa with a potential role in fertilization. AB - Eight monoclonal antibodies (McAbs), directed against antigens on rat cauda epididymal spermatozoa, were tested for their capacity to interfere with fertilization in vitro as a means of identifying molecules with a potential role in sperm-egg recognition and fusion. Antigens recognized by the McAbs were visualized on live spermatozoa by indirect immunofluorescence (IIF) and characterized by immunoblotting. Five McAbs (designated 1B5, 2C4, 4B5, 5B1, and 8C4) recognized antigens specifically on the sperm acrosome and three (designated 2B1, 2D6, and 6B2) bound to the flagellum. Of the eight McAbs investigated, three (2B1, 2C4, and 6B2) were effective in blocking fertilization in vitro when added as culture supernatants to mixtures of sperm and eggs. McAb 6B2 was inhibitory due to its ability to agglutinate spermatozoa. McAbs 2B1 and 2C4 did not agglutinate capacitated spermatozoa, had no observable effect on motility, and yet blocked fertilization in a dose-dependent manner. McAb 2C4 did not give a reaction on immunoblots, but the 2B1 antigen was identified as an Mr 40 kD glycoprotein. McAb 2B1 appeared to block fertilization at the level of zona binding, whereas the effects of 2C4 were directed more against zona penetration and/or fusion with the vitellus. When sperm-egg complexes were stained with 2C4 or 2B1 McAbs and viewed by IIF, all spermatozoa that were attached to the zona showed fluorescence on the head. These results suggest that different antigens on the rat sperm head participate in different aspects of the fertilization process and that during capacitation there is either exposure of these antigens or else they migrate to their site of action from the flagellum. PMID- 2184855 TI - Magnetic resonance imaging of the heart: a cardiologist's viewpoint. AB - Many noninvasive imaging methods for evaluating cardiac structure and function are available to cardiologists. MRI, however, is a newcomer on the scene and has not yet established a substantial niche in the day-to-day clinical management of patients or in providing data for basic and clinical research. The article explores the current and potential clinical and investigative applications of MRI and attempts to define the directions in which development should proceed to realize the full potential of this new methodology. PMID- 2184856 TI - Clinical magnetic resonance imaging of the vascular system. AB - Magnetic resonance imaging is extremely well suited to the diagnostic evaluation of the cardiovascular system. Over the past few years, more effective pulse sequences for imaging the heart and blood vessels have been developed, and although clinical use of cardiac MRI remains limited the use of MR angiographic techniques to evaluate major blood vessels is one of the fastest growing clinical applications of MRI today. The article reviews the current indications for vascular MRI with emphasis on those that are increasingly accepted by referring clinicians. PMID- 2184857 TI - Functional cardiovascular evaluation by magnetic resonance imaging. AB - The pursuit of capabilities for the evaluation of functional aspects of cardiovascular disease by MRI has resulted in the development and implementation of a number of interesting techniques that can be performed on a conventional scanner. Some currently available techniques emphasize the production of anatomically accurate images representing different phases of the cardiac cycle; others demonstrate physical changes within the acquired data that reflect motion, such as blood flow. Magnitude data from spin-echo and gradient-echo sequences can be used to produce dynamic images of the cardiovascular system. Phase data can be used to generate flow-based images reflecting the movement of blood protons. These techniques can be applied in the evaluation of ventricular function, valve function, or functional abnormalities in either congenital cardiovascular disease or great artery disease. PMID- 2184858 TI - Magnetic resonance imaging of congenital heart disease. AB - MRI has assumed an important role in the noninvasive evaluation of patients with congenital cardiac lesions. In this article, the authors examine basic technical considerations, an approach to analysis of MR images in congenital heart disease patients, and review major applications of MRI as they apply to patients with congenital heart disease. PMID- 2184859 TI - Sutures, staplers, leaks and strictures. A review of anastomoses in oesophageal resection at Royal Victoria Hospital, Belfast 1977-1986. AB - Leakage from an oesophagogastric anastomosis has a high morbidity and mortality. Recent evidence suggests that mechanical tissue stapling devices can decrease the rate of anastomotic breakdown but at the expense of an increase in the occurrence of fibrotic strictures at the anastomosis site. This study examines the rate of leakage and stricture in hand sutured and stapled anastomoses. A retrospective study was made of 221 oesophagogastric anastomoses following resection for carcinoma between 1977 and 1986. There were 122 sutured and 99 stapled anastomoses. Leak occurred in 21 sutured (17.2%) and 7 stapled (7.1%), P less than 0.05. If the stapled anastomosis was completely satisfactory and required no reinforcing sutures, the breakdown rate was in fact only 3% (2/69), P less than 0.01. A stapled anastomosis which required reinforcement had a similar chance of breakdown as a sutured anastomosis (16.7%). There was little difference in the performance of registrars in training and consultants at hand-sewn anastomoses with leakage rates of 13.7% and 18%, respectively; P greater than 0.05. The registrars, however, did not improve with the use of the stapler with a leakage rate of 14.3% compared to the consultants' rate of 1.75%, P less than 0.05. Involvement of the limits of resection with tumour slightly favoured breakdown- 15.5% compared to 11.6% if the limits were free from tumour, P greater than 0.05. The incidence of malignant strictures was similar in both groups but benign stricture was more common in the stapled group--13% (13/99) compared to 1.6% (2/122), P less than 0.01. The mechanical stapler brings uniformity to the anastomosis but cannot compensate for deficiencies in surgical technique. PMID- 2184860 TI - Transvaginal sonography in the first trimester: embryology, anatomy, and hCG correlation. PMID- 2184861 TI - Transvaginal sonography (TVS) PMID- 2184862 TI - Transvaginal sonography. PMID- 2184863 TI - Transvaginal ultrasound embryography. PMID- 2184864 TI - Transvaginal sonography in the abnormal first trimester. PMID- 2184865 TI - Technical aspects of vaginal ultrasound. PMID- 2184866 TI - Transvaginal sonography in evaluating ectopic pregnancy. PMID- 2184867 TI - The role of transvaginal ultrasound in the second and third trimesters. PMID- 2184868 TI - Transvaginal sonography: applications in infertility. PMID- 2184869 TI - [Experimental complex partial seizure and its possible clinical application]. AB - Clinical applications of experimental models of complex partial seizure were studied using kainic acid-induced limbic seizures and amygdaloid kindling models. The following experiments were done aiming to study the basic approach for the treatment of the intractable complex partial seizures. 1) Degenerative focal lesions were made in bilateral substantia nigra and substantia innominata by a local microinjection of the ibotenic acid and influences upon limbic seizures were studied. Substantia innominata has a facilitatory effect upon secondary generalization of the limbic seizure while substantia nigra has an inhibitory influence. Degenerative lesions of the bilateral hippocampus inhibited development process as well as establishment of the kindling. 2) Resection of the primary epileptic focus in a limbic seizure status resulted in seizure control in cats with a single focus but not in another with multiple foci. 3) An autoradiography was done during limbic seizure status induced by kainic acid microinjection, and local cerebral glucose utilization (LCGU) and local cerebral blood flow were studied in order to study the relationship between cerebral metabolism and cerebral blood flow during limbic seizures. In the pyramidal cell of the hippocampus, an increased ratio of LCGU (x 4.1) is larger than that of LCBF (x 1.6). This uncoupling may be one reason of the neuronal cell damage during the limbic seizure status. 4) Autoradiography of the calcium suggested that one of the causes of hippocampal degeneration in intractable complex partial seizures should be a consequence of calcium influx into pyramidal cells during repeated limbic seizures. PMID- 2184870 TI - [Neuropsychological and psychiatric problems in epileptic children]. AB - In the treatment of epileptic children, it is important to give considerations to the child's psychological aspects. One of considerations should be given to the neuropsychological disorders, since it is sometimes observed that learning disabilities coincide with epilepsy. Another consideration should be given to psychiatric disorders. Mental retardation occurs about 20% of epileptic children. Among personality and behavioral problems, hyperactivity is observed in younger children, while a viscous tendency is seen after puberty. The incidence of these two problems is related to the severity of mental retardation. In the course of the treatment of epileptic children, puberty is an important period. It is necessary to assist epileptic children to cope with the disease they have. Although the incidence is small, an acute or chronic epileptic psychosis is observed after puberty. An existence of pseudoseizures should not be forgotten. Cognitive or behavioral problems may occur as a result of anti-epileptic drugs. PMID- 2184871 TI - T-cell mediated cytolysis: evidence for target-cell suicide. AB - The mechanism by which cytotoxic T-lymphocytes (Tc) induce the death of specific target cells is still controversial. We have used quantitative cytochemical methods to distinguish the metabolic activities of the target cells from those of the Tc, even when they are attached to each other. Early events following Tc P8(15) target cell interaction were first, increased glucose 6-phosphate dehydrogenase activity and second, labilization of the lysosomes within the target cell: these changes could be mimicked, in part, by polyamines and could be inhibited by inhibiting ornithine decarboxylase (ODC) activity. The crucial role of ODC in the chain of events that led to cytolysis in this particular experimental system was shown first, by measuring ODC activity directly and secondly, by the inhibition of cytolysis by the presence of a selective inhibitor of ODC activity. PMID- 2184872 TI - The effects of cyclosporin A on glucose homeostasis and the kidney in the normal rat. AB - The effects of administering cyclosporin A (CsA), for periods of up to 84 days, on glucose homeostasis and renal function were studied in adult male Sprague Dawley rats. Marked glucose intolerance was demonstrated at a variety of drug doses, accompanied in the longer term by hyperglycaemia. Early on and at high CsA dose, the abnormal islet cell function was accompanied by islet cell vacuolation; in the long-term dose groups, more chronic structural islet changes were present. Although abnormalities in renal function and structure were noted during this study, they were not directly related to the pancreatic changes observed. PMID- 2184874 TI - Sensory integration and teacher-judged learning problems: a controlled intervention trial. AB - Seventy-four children from 21 schools referred because of teacher-perceived learning difficulties and prescreened for sensory integration (SI) deficits were given tests of SI, reading, vocabulary, perceptuo-motor function and motor development, and their teachers rated their classroom behaviour. The results showed that the children suffered primarily from attention deficit disorder without hyperactivity, and from mild deficits of SI. They were then divided into two groups matched approximately for sex, school and degree of SI deficits. One group received no treatment while the other was given about 13 weekly SI sessions, each of 1 h duration. All children were then reassessed on the same set of measures. There were significant improvements with time in both treated and untreated groups on most measures except classroom behaviour. Only one measure showed a treatment effect, though this one was most reflective of SI theory. PMID- 2184873 TI - Role of immunity to mycobacterial stress proteins in rheumatoid arthritis. AB - 'Stress Proteins in Inflammation' provided a forum for the discussion of topical issues in this rapidly moving field. The mycobacterial 65 kDa stress proteins play a key role in certain animal models of inflammatory arthritis. However, the impression emerging is that the mechanism probably involves more than a simple cross-reaction between mycobacterial SP65 and either the host SP65 or a cartilage antigen, and that evidence for a primary role in human rheumatoid arthritis is lacking. A realistic role for immune responses against stress proteins might be the amplification or perpetuation of inflammation. If so, this is unlikely to be limited to arthritis. PMID- 2184875 TI - Regional cerebral blood flow velocity patterns in newborn infants. AB - Using range-gated pulsed Doppler sonography, cerebral blood flow velocity (CBFV) waveforms from the anterior cerebral artery (ACA), middle cerebral artery (MCA) and circle of Willis artery (CW) were examined in a total of 34 newborn infants. We compared the pulsatility index (PI) from the three cerebral arteries sampled in 10 term and 10 preterm (29 +/- 2 weeks) newborn infants without a history of perinatal asphyxia or intracranial pathology. The Pl in the ACA ranged from 0.60 to 1.03. There were no significant differences in Pl between the three vessels by paired comparisons. The Pl of the MCA differed from that of the ACA by 0.00 +/- 0.05. The variation coefficient (CV) was 7%. For CW with ACA, the difference was 0.00 +/- 0.04 and CV was 6%. Both intra- and interexaminer variation in Pl measurements were studied in another 14 infants. The variation coefficients were 5-8% for all three cerebral arteries. We showed that CBFV waveform patterns were similar in regional cerebral arteries, with Pl being a consistent CBFV index. In normal cerebral circulation, the intervessel Pl differences were within observer variations. Deviation from this may suggest abnormal regional cerebral haemodynamics. PMID- 2184876 TI - Lung cancer--still a long road ahead. PMID- 2184877 TI - An overview in the treatment of advanced ovarian cancer. MRC Gynaecological Cancer Working Party. PMID- 2184878 TI - Intravesical therapy in the management of superficial transitional cell carcinoma of the bladder: the experience of the EORTC GU Group. PMID- 2184879 TI - Use of MoAb D612 in combination with a panel of MoAb for the immunocytochemical identification of metastases from colon-rectum carcinoma. AB - During the course of colon-rectum tumours a number of clinical events may occur in which conventional cytopathology can provide only a partial contribution to the definition of a differential diagnosis, i.e. effusions, distant recurrences and second neoplasias. In the present study we have evaluated whether monoclonal antibody (MoAb) D612, recognising a colon-rectum associated antigen, can be used in this context. To this end, MoAb D612 was employed in combination with a panel of MoAb of well defined tumour specificity in immunocytochemical tests. The immunocytochemical findings obtained were compared with the histological and clinical diagnosis. Of 62 effusions and 40 fine needle aspirates studied, MoAb D612 reactivity correlated with the correct diagnosis in 92.8% of the instances. These results indicate that this reagent may help to improve the current cytopathological diagnosis of colon-rectum tumours by identifying the colonic origin of metastases in patients with unknown primary tumour, differentiating ovarian carcinoma from colon metastases to the ovaries and establishing the presence of a second neoplasia in patients with a previous history other than colon carcinoma. PMID- 2184880 TI - Cellular localisation of tumour antigen (TA-4) in normal, dysplastic and neoplastic squamous epithelia of the upper aerodigestive tract. AB - We report the use of tumour antigen (TA-4) polyclonal antiserum to assess the level and pattern of TA-4 antigen expression in formalin-fixed paraffin-embedded tissue sections from 110 patients with a range of normal, dysplastic and malignant squamous epithelia from various sites in the upper aerodigestive tract. There was a high degree of TA-4 antigen expression in the superficial layers of normal squamous epithelium and in well-differentiated squamous cell cancers (SCC). TA-4 expression was consistently absent in dysplastic oral squamous epithelium and in poorly differentiated SCCs. The degree of cellular heterogeneity in moderately differentiated SCCs was such that morphologically identical squamous cancer cells could be distinguished on the basis of TA-4 expression. Immuno-electron microscopy localised TA-4 antigen to tonofibrils in both normal buccal (squamous) cells and in squamous cancer cells. Results of Western blotting confirmed the presence of a 48 kDa protein consistent with TA-4 antigen in both SCCs and in normal buccal mucosa. We conclude that TA-4 protein is a normal cellular component, that cellular TA-4 expression is related to the level of cellular differentiation in squamous epithelia and that it is not likely to be useful as an independent index of cellular proliferation or malignant behaviour. PMID- 2184882 TI - Maintaining a balanced treatment approach with the borderline patient. AB - There has been an ongoing controversy in the nature of the recommended treatment for the borderline personality disorder early in therapy. Kernberg emphasizes the negative features of the transference early in therapy and recommends dealing with it primarily by interpretation, confrontation, and limit setting. Adler views the transference early in therapy as primarily reflecting subjectively perceived breakdowns in needed self-object merger, and recommends creating a symbolic holding environment through empathy and support. Gunderson devotes more equal emphasis to empathizing with and challenging the patient's point of view. The balance between empathy and confrontation is difficult to maintain because of the counter-transference pull of the borderline. In order to avoid bias toward empathic or confrontive treatment strategies, it is argued that one must pay special attention to the extent to which the therapist understands the plausibility and adaptiveness of the borderline patient's experience and behaviour as readily as the implausibility and maladaptiveness. PMID- 2184881 TI - How nephrotoxic is carboplatin? PMID- 2184883 TI - Cumulative index. Volumes 51-62 (1984-1989). PMID- 2184884 TI - Progress with Laue diffraction studies on protein and virus crystals. PMID- 2184885 TI - Mechanistic studies of peptidyl prolyl cis-trans isomerase: evidence for catalysis by distortion. AB - Cyclophilin, the cytosolic binding protein for the immunosuppressive drug cyclosporin A, has recently been shown to be identical with peptidyl prolyl cis trans isomerase [Fischer, G., Wittmann-Liebold, B., Lang, K., Kiefhaber, T., & Schmid, F.X. (1989) Nature 337, 476; Takahashi, N., Hayano, T., & Suzuki, M. (1989) Nature 337, 473]. To provide a mechanistic framework for studies of the interaction of cyclophilin with cyclosporin, we investigated the mechanism of the PPI-catalyzed cis to trans isomerization of Suc-Ala-Xaa-cis-Pro-Phe-pNA (Xaa = Ala, Gly). Our mechanistic studies of peptidyl prolyl cis-trans isomerase include the determination of steady-state kinetic parameters, pH and temperature dependencies, and solvent and secondary deuterium isotope effects. The results of these experiments support a mechanism involving catalysis by distortion in which the enzyme uses free energy released from favorable, noncovalent interactions with the substrate to stabilize a transition state that is characterized by partial rotation about the C-N amide bond. PMID- 2184886 TI - Three-dimensional structure of interleukin 8 in solution. AB - The solution structure of the interleukin 8 (IL-8) dimer has been solved by nuclear magnetic resonance (NMR) spectroscopy and hybrid distance geometry dynamical simulated annealing calculations. The structure determination is based on a total of 1880 experimental distance restraints (of which 82 are intersubunit) and 362 torsion angle restraints (comprising phi, psi, and chi 1 torsion angles). A total of 30 simulated annealing structures were calculated, and the atomic rms distribution about the mean coordinate positions (excluding residues 1-5 of each subunit) is 0.41 +/- 0.08 A for the backbone atoms and 0.90 +/- 0.08 A for all atoms. The three-dimensional solution structure of the IL-8 dimer reveals a structural motif in which two symmetry-related antiparallel alpha helices, approximately 24 A long and separated by about 14 A, lie on top of a six stranded antiparallel beta-sheet platform derived from two three-stranded Greek keys, one from each monomer unit. The general architecture is similar to that of the alpha 1/alpha 2 domains of the human class I histocompatibility antigen HLA A2. It is suggested that the two alpha-helices form the binding site for the cellular receptor and that the specificity of IL-8, as well as that of a number of related proteins involved in cell-specific chemotaxis, mediation of cell growth, and the inflammatory response, is achieved by the distinct distribution of charged and polar residues at the surface of the helices. PMID- 2184887 TI - Kinetics of binding of single-stranded DNA binding protein from Escherichia coli to single-stranded nuclei acids. AB - The time course of the reaction of Escherichia coli single-stranded DNA binding protein (E. coli SSB) with poly(dT) and M13mp8 single-stranded DNA has been measured by fluorescence stopped-flow experiments. For poly(dT), the fluorescence traces follow simple bimolecular behavior up to 80% saturation of the polymer with E. coli SSB. A mechanistic explanation of this binding behavior can be given as follows: (1) E. coli SSB is able to translocate very rapidly on the polymer, forming cooperative clusters. (2) In the rate-limiting step of the association reaction, E. coli SSB is bound to the polymer only by one or two of its four contact sites. As compared to poly(dT), association to single-stranded M13mp8 phage DNA is slower by at least 2 orders of magnitude. We attribute this finding to the presence of secondary structure elements (double-stranded structures) in the natural single-stranded DNA. These structures cannot be broken by E. coli SSB in a fast reaction. In order to fulfill its physiological function in reasonable time, E. coli SSB must bind newly formed single-stranded DNA immediately. The protein can, however, bind to such pieces of the newly formed single-stranded DNA which are too short to cover all four binding sites of the E. coli SSB tetramer. PMID- 2184888 TI - Characterization of the multiple catalytic activities of tartrate dehydrogenase. AB - Tartrate dehydrogenase (TDH) has been purified to apparent homogeneity from Pseudomonas putida and has been demonstrated to catalyze three different NAD(+) dependent reactions. TDH catalyzes the oxidation of (+)-tartrate to form oxaloglycolate and the oxidative decarboxylation of D-malate to form pyruvate and CO2. D-Glycerate and CO2 are formed from meso-tartrate in a reaction that is formally a decarboxylation with no net oxidation or reduction. The steady-state kinetics of the first two reactions have been investigated and found to follow primarily ordered mechanisms. The pH dependence of V and V/K was determined and indicates that catalysis requires that a base on the enzyme with a pK of 6.7 be unprotonated. TDH activity requires a divalent and a monovalent cation. Kinetic data suggest that the cations function in substrate binding and facilitation of the decarboxylation of beta-ketoacid intermediates. PMID- 2184889 TI - Transfer of preformed terminal C5b-9 complement complexes into the outer membrane of viable gram-negative bacteria: effect on viability and integrity. AB - An efficient fusion system between Gram-negative bacteria and liposomes incorporating detergent-extracted C5b-9 complexes has been developed that allows delivery of preformed terminal complexes to the cell envelope (Tomlinson et al., 1989b). Fusion of Salmonella minnesota Re595 and Escherichia coli 17 with C5b-9 incorporated liposomes resulted in the transfer of 1900 C5b-9 complexes to each target bacterial cell. No loss in viability of bacteria was observed following fusion, even though the deposotion of 900 complexes onto the envelope following exposure to lysozyme-free serum effected a greater than 99% loss of viability. Increased sensitivity to antibiotics normally excluded from the cell by an integral outer membrane (OM), as well as the ability of the chromogenic substrate PADAC to gain access to periplasmically located beta-lactamase, indicated that transferred C5b-9 complexes functioned as water-filled channels through the OM. A similar conclusion was drawn from measurements demonstrating the uptake by cells of the lipophilic cation tetraphenylphosphonium (bromide), a result further indicating that the membrane potential across the cytoplasmic membrane was maintained following C5b-9 transfer to the OM. Examination of S. minnesota Re595 by electron microscopy revealed no obvious difference between cells exposed to lethal concentrations of lysozyme-free serum and cells following fusion with C5b 9-incorporated liposomes. These data suggest either that there are critical sites in the OM to which liposome-delivered C5b-9 complexes are unable to gain access or that bacterial cell death is related to events occurring during polymerization of C9 on the cell surface. PMID- 2184890 TI - Expression, purification, and characterization of human factor XIII in Saccharomyces cerevisiae. AB - Factor XIII is the terminal enzyme of the clotting cascade. A cDNA sequence encoding human placental factor XIII was expressed in Saccharomyces cerevisiae with the yeast ADH2-4c promoter. Expression levels were a strong function of the noncoding flanking DNA content of the construction. When the terminal 3'-flanking noncoding DNA was removed, expression increased approximately 50-fold. The protein was produced in quantity by high-yield fermentation and purified to homogeneity. The recombinant protein was cleaved by thrombin at the same activation site as purified human placental FXIII and exhibited 100% enzymatic activity. At high thrombin concentrations rFXIIIa was cleaved into inactive 54- and 25-kDa polypeptides. The identity of these cleavage sites and the blocked N terminus to that of the human protein was revealed by amino acid microsequencing. A time course of thrombin activation was performed and the relative distribution of the thrombin-cleaved subunits to the uncleaved zymogen subunits determined; the results were consistent with the half of the sites catalytic model for transglutaminase activity proposed by Chung et al. (Chung, S. I., Lewis, M. S., & Folk, J. E. (1974) J. Biol. Chem. 249, 940-950, 1974) and Hornyak et al. (Hornyak, T. J., Bishop, P. D., & Shafer, J. A. (1989) Biochemistry 28, 7326 7332). Equilibrium and velocity sedimentation analysis indicated that rFXIII exists as a 166-kDa nondissociating dimer that behaves as a compact particle of 8.02 S. Thus, all of the properties of rFXIII thus far examined are consistent with those reported for human platelet and placental FXIII.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2184891 TI - The transformed glucocorticoid receptor has a lower steroid-binding affinity than the nontransformed receptor. AB - High-salt treatment of cytosolic glucocorticoid receptor (GR) preparations reduces the steroid-binding ability of the receptor and induces the conversion of the receptor from a nontransformed (non-DNA-binding) 9S form to a transformed (DNA-binding) 4S entity. Therefore, we decided to investigate the possible relationship between these two phenomena. Steroid-free GR was converted from a 9S to a 4S form by exposure to 0.4 M NaCl. The binding of [3H]triamcinolone acetonide [( 3H]TA) to the 9S form was almost saturated at a concentration of 20 nM, whereas [3H]TA was hardly bound to the 4S form at this concentration. The 4S form was efficiently labeled at 200 nM. Scatchard analysis of the GR exposed to 0.4 M NaCl in the presence of 10 mM molybdate showed the presence of two types of binding sites with apparent dissociation constants of 0.52 +/- 0.07 and 64.1 +/- 16.2 nM, respectively. In the absence of molybdate, the ratio of the lower affinity site was increased, but the total number of binding sites was not modified. The GR with the low [3H]TA-binding affinity bound to DNA-cellulose even in its unliganded state, whereas the form with the high affinity did not. Immunoblot analysis using anti-GR monoclonal antibody revealed no difference in molecular size (Mr 94000) between the high- and low-affinity entities. These results indicate that the transformed GR has a reduced [3H]TA-binding affinity as compared to the nontransformed GR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2184892 TI - Reversible dissociation and unfolding of aspartate aminotransferase from Escherichia coli: characterization of a monomeric intermediate. AB - The unfolding and dissociation of the dimeric enzyme aspartate aminotransferase (D) from Escherichia coli by guanidine hydrochloride have been investigated at equilibrium. The overall process was reversible, as judged from almost complete recovery of enzymic activity after dialysis of 0.7 mg of denatured protein/mL against buffer. Unfolding and dissociation were monitored by circular dichroism and fluorescence spectroscopy and occurred in three separate phases: D in equilibrium 2M in equilibrium 2M* in equilibrium 2U. The first transition at about 0.5 M guanidine hydrochloride coincided with loss of enzyme activity. It was displaced toward higher denaturant concentrations by the presence of either pyridoxal 5'-phosphate or pyridoxamine 5'-phosphate and toward lower denaturant concentrations by decreasing the protein concentration. Therefore, bound coenzyme stabilizes the dimeric state, and the monomer (M) is inactive because the shared active sites are destroyed by dissociation of the dimer. M was converted to M* and then to the fully unfolded monomer (U) in two subsequent transitions. M* was stable between 0.9 and 1.1 M guanidine hydrochloride and had the hydrodynamic radius, circular dichroism, and fluorescence of a monomeric, compact "molten globule" state. PMID- 2184893 TI - Chromophore topography and secondary structure of 124-kilodalton Avena phytochrome probed by Zn2(+)-induced chromophore modification. AB - The relative extent of chromophore exposure of the red-absorbing (Pr) and far-red absorbing (Pfr) forms of 124-kDa oat phytochrome and the secondary structure of the phytochrome apoprotein have been investigated by using zinc-induced modification of the phytochrome chromophore. The absence of bleaching of Pr in the presence of a 1:1 stoichiometric ratio of zinc ions, in contrast to extensive spectral bleaching of the Pfr form, confirms previous reports of differential exposure of the Pfr chromophore relative to the Pr chromophore [Hahn et al. (1984) Plant Physiol. 74, 755-758]. The emission of orange fluorescence by zinc chelated Pfr indicates that the Pfr chromophore has been modified from its native extended/semi-extended conformation to a cyclohelical conformation. Circular dichroism (CD) analyses of native phytochrome in 20 mM Tris buffer suggests that the Pr-to-Pfr phototransformation is accompanied by a photoreversible change in the far-UV region consistent with an increase in the alpha-helical folding of the apoprotein. The secondary structure of phytochrome in Tris buffer, as determined by CD, differs slightly from that of phytochrome in phosphate buffer, suggesting that phytochrome is a conformationally flexible molecule. Upon the addition of a 1:1 molar ratio of zinc ions to phytochrome, a dramatic change in the CD of the Pfr form is observed, while the CD spectrum of the Pf form is unaffected. Analysis of the bleached Pfr CD spectrum by the method of Chang et al. (1978) reveals that chelation with zinc ions significantly alters the secondary structure of the phytochrome molecule, specifically by increasing the beta-sheet content primarily at the expense of alpha-helical folding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2184894 TI - The LexA repressor and its isolated amino-terminal domain interact cooperatively with poly[d(A-T)], a contiguous pseudo-operator, but not with random DNA: a circular dichroism study. AB - The interaction of the entire LexA repressor and its amino-terminal DNA binding domain with poly[d(A-T)] and random DNA has been studied by circular dichroism. Binding of both protein species induces an about 2-fold increase of the positive circular dichroism band at about 270 nm of both polynucleotides, allowing a precise determination of the principal parameters as a function of mono- and divalent salt concentration and pH. Both proteins interact much more strongly (about 2000-fold) with poly[d(A-T)] than with random DNA as expected from the homology with the specific consensus binding site of LexA (CTGTATATATATACAG). For both LexA and its DNA binding domain we find that the interaction with poly[d(A T)] is cooperative with a cooperativity factor omega of about 50-70 for both proteins over a wide range of solvent conditions, suggesting that the carboxy terminal domain of LexA is not involved in this type of cooperativity. On the contrary, no cooperativity could be detected for the interaction of the LexA DNA binding domain with a random DNA fragment. The overall binding constant K omega (or simply K in the case of random DNA) depends strongly on the salt concentration as observed for most protein-DNA interactions, but the behavior of LexA is unusual in that the steepness of this salt dependence (delta log K omega/delta log [NaCl]) is much more pronounced at slightly acidic pH values as compared to that at neutral or slightly alkaline pH. The behavior is not easily understood in terms of the current theories on the electrostatic contribution to protein-DNA interactions on the basis of polyelectrolyte theory. A comparison of the overall binding constant K omega of the entire LexA repressor and its DNA binding domain reveals that LexA binds only 20-50-fold stronger under a wide variety of salt and pH conditions. This result tends to demonstrate further that the additional energy due to the dimerization of LexA via the carboxy-terminal domain should be rather weak as expected from the small dimerization constant of LexA (2 X 10(-4) M-1). PMID- 2184895 TI - Nature of the primary photochemical events in rhodopsin and bacteriorhodopsin. PMID- 2184896 TI - Anaerobic metabolism in aerobic mammalian cells: information from the ratio of calorimetric heat flux and respirometric oxygen flux. AB - Calorimetric and respirometric studies of cultured cells show that both neoplastic and non-neoplastic cell types maintain an anaerobic contribution to their total heat flux. In many mammalian cells this can be explained quantitatively by lactate production observed under fully aerobic conditions. Uncoupling and enhanced futile substrate cycling increase the ratio of heat flux to oxygen flux, the calorimetric-respirometric (CR) ratio. The interpretation of calorimetric and respirometric measurements requires an energy balance approach in which experimentally measured CR ratios are compared with thermochemically derived oxycaloric equivalents. The oxycaloric equivalent is the enthalpy change per mole of oxygen consumed, and equals -470 kJ/mol O2 in the aerobic catabolism of glucose, assuming that catabolism is 100% dissipative (the net efficiency of metabolic heat transformation is zero). CR ratios more negative than -470 kJ/mol O2 have been reported in well-oxygenated cell cultures and are discussed in terms of integrated aerobic and anaerobic metabolism. PMID- 2184897 TI - Iron-reductases in the yeast Saccharomyces cerevisiae. AB - Several NAD(P)H-dependent ferri-reductase activities were detected in sub cellular extracts of the yeast Saccharomyces cerevisiae. Some were induced in cells grown under iron-deficient conditions. At least two cytosolic iron-reducing enzymes having different substrate specificities could contribute to iron assimilation in vivo. One enzyme was purified to homogeneity: it is a flavoprotein (FAD) of 40 kDa that uses NADPH as electron donor and Fe(III)-EDTA as artificial electron acceptor. Isolated mitochondria reduced a variety of ferric chelates, probably via an 'external' NADH dehydrogenase, but not the siderophore ferrioxamine B. A plasma membrane-bound ferri-reductase system functioning with NADPH as electron donor and FMN as prosthetic group was purified 100-fold from isolated plasma membranes. This system may be involved in the reductive uptake of iron in vivo. PMID- 2184898 TI - Structure of ribosomes from Thermomyces lanuginosus by electron microscopy and image processing. AB - Multivariate statistical analysis and hierarchical ascendant classification techniques have been used to sort electron images of ribosomes from the thermophilic fungus Thermomyces lanuginosus into their characteristic views. Three predominant views were elucidated, called here overlap, non-overlap and top, showing reproducible detail approaching 1.8 nm resolution. The overlap and non-overlap forms of the fungal ribosomes appeared to be similar to those from the eubacterium Escherichia coli, despite differences in rRNA composition. The non-overlap projection predominated for the fungal complexes, suggesting different adsorption properties for ribosomes from the two species. Additionally, the top view has not been previously described for eubacteria. No major morphological differences could be detected between the fungal and eubacterial ribosomes at the resolution achieved in this study, suggesting a strong conservation of tertiary structure of this macromolecular complex despite the evolutionary gap between these two organisms. PMID- 2184899 TI - Effects of dexamethasone on the availability of L-tryptophan and on the insulin and FFA concentrations in unipolar depressed patients. AB - Several authors have shown that the availability of L-tryptophan (L-TRP) in the serum is lower in patients with major depression than in controls. It has recently been reported that the administration of a dose of dexamethasone sufficient to cause cortisol suppression also caused significant decrements in the availability of L-TRP. In order to elucidate the putative pathophysiological mechanisms underlying this decreased L-TRP disposition, the authors examined 37 depressed women categorized according to the DSM-III. L-TRP, the sum of five competing amino acids (CAA), the L-TRP/CAA ratio, and insulin and free fatty acid (FFA) levels were determined both before and after oral administration of 1 mg dexamethasone. The availability of L-TRP was significantly lower in depressed women with melancholia compared with simple major and minor depressives. The baseline disposal of L-TRP was related neither to insulin nor to FFA concentrations Dexamethasone administration significantly reduced the L-TRP and L TRP/CAA values and increased FFA and insulin levels. Postdexamethasone L-TRP and FFA levels were significantly and positively correlated. PMID- 2184900 TI - Molecular basis of vitamin K-dependent gamma-carboxylation. PMID- 2184901 TI - Treatment of poor-prognosis, newly diagnosed acute myeloid leukemia with ara-C and recombinant human granulocyte-macrophage colony-stimulating factor. AB - We administered recombinant granulocyte-macrophage colony-stimulating factor (GM CSF) (120 micrograms/m2/d by continuous intravenous [IV] infusion) to 12 patients with newly diagnosed acute myeloid leukemia (AML) at relatively high risk of early death during remission induction. GM-CSF began 3 days after completion of induction chemotherapy (ara-C 1.5 g/m2 d x 4 days by continuous IV infusion after a 3 g/m2 bolus). Rates of fatal infection (42%), pneumonia and/or sepsis (83%), and CR (50%) did not differ significantly (P less than .05) from those observed after administration of the identical chemotherapy without GM-CSF to 53 historical controls with newly diagnosed AML at similarly high risk of early death. There were no significant differences between the GM-CSF-treated and the historical groups in the time required to reach neutrophil counts of 500 or 1,000/microL after administration of chemotherapy. Four patients died of infection before they could have benefited from the earliest recovery of neutrophil count observed in patients who entered CR. Growth of leukemia after GM CSF administration was observed in only 1 of the 8 patients who survived long enough for response to induction therapy to be fully evaluated. This observation suggests that it might be safe to undertake larger, randomized studies, perhaps using earlier administration of GM-CSF, to definitively determine the role of GM CSF added to chemotherapy in patients with newly diagnosed AML. PMID- 2184902 TI - Regulation of human eosinophil precursor production by cytokines: a comparison of recombinant human interleukin-1 (rhIL-1), rhIL-3, rhIL-5, rhIL-6, and rh granulocyte-macrophage colony-stimulating factor. AB - The effect of a panel of recombinant human (rh) cytokines on the generation of human eosinophil precursors was assessed using a two-step culture technique. Normal human bone marrow was preincubated with different cytokine combinations in liquid culture before assessment of the number of eosinophil progenitors, which give rise to eosinophil colony-forming units (CFU-Eo) on secondary semi-solid culture with either interleukin-5 (IL-5), IL-3, or granulocyte-macrophage colony stimulating factor. rhIL-3 or rhGM-CSF, but not rhIL-5, increased the number of CFU-Eo. CFU-Eo production by rhIL-3 or rhGMCSF was maximal after 7 days' preincubation. Neither rhIL-1 or rhIL-6 acted on eosinophil precursors, either alone or in combination with rhIL-5, rhIL-3, or rhGM-CSF. A similar spectrum of activity of the cytokines was demonstrated whether rhIL-5, rhIL-3, or rhGM-CSF was used in the secondary cultures as the eosinophil CSF. However, rhIL-3 induced relatively more rhIL-5-responsive CFU-Eo than rhIL-3-responsive CFU-Eo, suggesting that rhIL-3 is pushing progenitors into an rhIL-5-responsive compartment. PMID- 2184903 TI - Regulation of autoimmune anti-platelet antibody-mediated adhesion of monocytes to platelet GPIIb/GPIIIa: effect of armed monocytes and the Mac-1 receptor. AB - Platelet autoantigen-autoantibody-monocyte interaction was studied by utilization of a specific monoclonal antibody (MoAb) 10E5 to trap and immobilize the GPIIb GPIIIa complex on microtiter plates. Peripheral blood mononuclear cells (PBMC) or purified monocytes formed distinct morphologic clusters after incubation with immobilized antigen for 18 hours at 37 degrees C. PBMC of 18 and 19 patients with autoimmune thrombocytopenic purpura (ATP) formed 48 +/- 6.8 (SEM) clusters/well compared with 7.4 +/- 1.0 for control subjects, P less than .001. The number of clusters per well correlated inversely and exponentially with platelet count, r = -.8, n = 21, indicating that the GPIIb-GPIIIa autoantigen is pathophysiologically relevant. Binding of ATP PBMC to immobilized GPIIb-GPIIIa could be inhibited by F(ab')2 fragments of immunoglobulin (Ig) G of ATP patients, indicating that monocyte IgG bound to autoantigen by its F(ab')2 domain. Optimal cluster formation could be obtained with normal monocytes if preincubated with ATP IgG but not with F(ab')2 fragments of ATP IgG, indicating that ATP IgG binds to monocytes by its Fc domain. Armed monocytes (ie, normal monocytes preincubated with ATP IgG) bound to immobilized autoantigen 5.8-fold greater than normal monocytes incubated with immobilized autoantigen opsonized with ATP IgG. Armed monocyte adhesion could be inhibited 81% from 18.9 +/- 1.6 to 3.6 +/- 0.5 clusters/well by prior fixation with 0.1% formalin, whereas fixation of IgG before arming of monocytes was not inhibitory. MoAb MM41, directed against the alpha m-chain of the Mac-1 adhesive protein receptor of monocytes, inhibited cluster formation by 79%. Thus, (1) armed monocyte interaction with autoantigen is considerably more effective than monocyte interaction with opsonized autoantigen; (2) armed monocyte interaction requires specific F(ab')2-antigen recognition; and (3) monocyte-autoantigen interaction requires a secondary nonimmunologic adhesive event. PMID- 2184904 TI - Reticulocytes II: Reexamination of the in vivo survival of stress reticulocytes. AB - Very young reticulocytes are released into the circulation in response to the stress of anemia. These stress reticulocytes have shortened in vivo survival when transfused into normal recipients, and are generally considered to be abnormal because they have skipped a terminal cell division. We reevaluated one aspect of their abnormality: that of in vivo survival. Using methodology that accounted for all cells transfused, in vivo survival of both normal and stress reticulocytes was investigated in both normal and anemic recipients. The experiments demonstrate that: (1) survival of reticulocytes is normal only when normal reticulocytes are injected into nonanemic animals; (2) intrinsic properties of stress reticulocytes lead to their immediate removal from the circulation by normal recipients to a significantly greater extent than by anemic recipients; and (3) both stress and normal reticulocytes are removed at an accelerated rate over time by anemic recipients. Taken together, the data indicate that in the course of becoming anemic, an adaptation occurs that allows cells produced during anemia to circulate considerably longer in anemic animals than they could in normal nonanemic animals. Other studies disclosed that increased reticulocyte survival in anemic animals could not be attributed to reticuloendothelial overload, but is induced by adaptation of the spleen, decreasing its removal of stress reticulocytes. PMID- 2184905 TI - Isotope dilution studies: determination of carbon-13, nitrogen-15 and deuterium enriched compounds using capillary gas chromatography-chemical reaction interface/mass spectrometry. AB - In addition to the ability of a capillary gas chromatographic-chemical reaction interface/mass spectrometric technique (CRIMS) to detect the presence of 13C, 15N and 2H (D) it can also quantify the level of the enriched substance. The microwave-powered chemical reaction interface converts materials from their original forms into small molecules whose mass spectra serve to identify and quantify the nuclides which make up each analyte. The presence of enrichment of each element is followed by monitoring the isotopic variants of CO2, NO or H2 which are produced in the chemical reaction interface. Chromatograms showing only enriched 13C and 15N are produced by subtracting the abundance of naturally occurring isotopes from the observed M + 1 signal. A selective chromatogram of 2H (D) is obtained by measuring HD at m/z 3.0219 with a resolution of 2000. Enrichment of 13C and 15N is quantified by measuring the ratio of excess 13CO2 to total 12CO2 or excess 15NO to total 14NO. To evaluate linearity and detection limits, we have used phenytoin as an example of an unlabeled substance and added various labeled phenytoin analogs. Atom enrichments of 0.3% were detectable for (2,4,5-13C3) phenytoin and 0.06% for (1,3-15N2)labeled phenytoin, each in the presence of 500 ng of unlabeled phenytoin, respectively. For deuterium, enrichment could not be directly determined. However, 1 ng of (ring D10) phenytoin was determined in the presence of 500 ng of unlabeled diethylated phenytoin. We have found CRIMS capable of quantifying 13C-, 15N- and D-enriched substances. PMID- 2184906 TI - Embryonic stem cells as targets for gene transfer: a new approach to molecular manipulation of the murine hematopoietic system. AB - Recent advances in the ability to introduce exogenous DNA sequences into specific chromosomal locations in mammalian cells via homologous recombination together with effective manipulation of murine embryos and embryo-derived cell lines (ES cells) make possible the generation of mouse stains with specific genes disrupted. Such gene targeting methods will allow replacement of normally functioning murine genes with genes altered with precise mutations involving many aspects of gene expression, including transcription, processing and protein protein interactions. ES cell technology will allow experimental hematologists to produce animal models for human hematopoietic diseases and explore the role of complex proteins involved in hematopoiesis in vivo. PMID- 2184907 TI - The use of recombinant cytokines for enhancing immunohematopoietic reconstitution following bone marrow transplantation. II. The influence of lymphokines on CFU-GM colonies from human untreated, ASTA-Z or Campath-1M treated bone marrow. AB - Patients undergoing bone marrow transplantation (BMT) are subjected to the risk of pancytopenia in the immediate post-BMT period. Recipients of bone marrow (BM) autografts purged in vitro by chemical agents such as mafosfamide (ASTA-Z) are even more likely to develop a delayed engraftment. In a previous study in mice, we showed earlier immunohematopoietic reconstitution after syngeneic marrow grafting with BM cells precultured with single or combined cytokines. In this work we determined optimal culture conditions for the use of single and various cytokine combinations in order to activate progenitor cells following in vitro cultures of untreated, ASTA-Z purged or T cell-depleted human BM preparations prior to BMT. The best single cytokine for enhancing CFU-GM was found to be GM CSF (0.1 mg/ml) which produced an increase of up to 8-fold over controls after 3 days' incubation. Addition of recombinant human interleukin 3 (rhIL3) (0.1 mg/ml) to rhGM-CSF had an additive effect. The same enhancing effect of in vitro CFU-GM by both cytokines was observed following ASTA-Z purging of BM cells obtained from patients undergoing autologous BMT. Similarly, depletion of lymphocytes from BM using the monoclonal rat anti-human lymphocyte antibody Campath-1M and human complement did not diminish the beneficial influence of rhIL3 and rhGM-CSF. When combined with rhGM-CSF and rhIL3, rhIL1 and rhIL2 had no appreciable enhancing effect on CFU-GM and occasionally even reduced it. We suggest that enhancement of differentiation of hematopoietic progenitor cells may be accomplished by in vitro incubation of BM cells without continuous administration of cytokines in vivo following BMT. PMID- 2184908 TI - Options and limitations of long-term oral ciprofloxacin as antibacterial prophylaxis in allogeneic bone marrow transplant recipients. AB - The efficacy and safety of ciprofloxacin as long-term antibacterial prophylaxis after allogeneic bone marrow transplantation were assessed prospectively. Eighty nine recipients of lymphocyte-depleted marrow grafts were each given ciprofloxacin orally, 500 mg twice daily. Fever developed in 71 out of 78 evaluable patients (91%) and was accompanied by positive blood cultures in 42 cases (59%). 'Viridans' streptococci, all but one with reduced in vitro susceptibility to ciprofloxacin, accounted for 35 episodes of bacteraemia. Thirty three episodes occurred in patients given anthracyclines compared with only two episodes in other patients (chi 2 = 5.58: p less than 0.05). All bacteraemic fevers occurred within 11 days post-transplant. Gram-negative sepsis did not occur in any patient. Sixteen patients died but none due to a bacterial cause. Allergy to ciprofloxacin was registered in three out of 76 assessable cases (4%). PMID- 2184909 TI - Effect of steroid therapy in experimental head trauma. AB - Since steroid therapy has been mostly utilized on an empirical basis in the management of head injury, this experimental study to assess the efficacy of steroid therapy was performed. Swiss-Webster mice (n = 85) were given 0.2 m of 50% ethanol intraperitoneally (IP) and lightly anaesthetized with ether. Ten randomly chosen mice were set aside and received no further treatment (non-head injury controls: Group A). The remaining mice (n = 75) were subjected to head injury and the survivors at 30 minutes (n = 52) were assigned randomly to two Groups, B and C. Group B was given 0.1 ml of saline IP at 30 minutes, 28 hours and 48 hours post-injury. At similar time intervals, animals in Group C received methylprednisolone 30 mg/kg IP. All animals were observed up to seven days and the number of survivors in each group recorded. All ten animals in Group A survived seven days. The daily mortality in Groups B and C were similar, and all animals were dead at seven days. Steroids were not found to be efficacious in this animals model. PMID- 2184910 TI - The effects of cromakalim on ATP-sensitive potassium channels in insulin secreting cells. AB - 1. The single-channel current recording technique has been used to investigate the effects of cromakalim, diazoxide and ATP, separately and combined, on the opening of ATP-sensitive potassium channels in the insulin-secreting cell-line RINm5F. The actions of these drugs have been studied using the permeabilized open cell variation of the patch-clamp technique. 2. In the absence of internal ATP, cromakalim (80-200 microM) was unable to open ATP-sensitive K+ channels but when ATP was present both cromakalim and diazoxide caused channel openings. 3. Interactions between ATP and cromakalim seemed competitive. Concentrations of cromakalim in the range 80-200 microM readily activated channels inhibited by 0.1 mM ATP, but had no effects when the concentration of ATP was increased to 0.5-2 mM. Only when the concentration of cromakalim was increased to 400-800 microM could opening of 0.5-2 mM ATP-inhibited channels be regularly observed. In the continued presence of cromakalim (400-800 microM), an increase in the internal concentration of ATP from either 0.25 to 0.5 mM or 1 to 2 mM, inhibited cromakalim-activated K+ channels. 4. Activation of ATP-inhibited K+ channels was abolished by replacing ATP with ATP gamma S and cromakalin had no effects on ATP gamma S-inhibited channels. This suggests that cromakalim may open KATP channels in insulin-secreting cells by a mechanism which involves protein phosphorylation. PMID- 2184911 TI - Action of calcitonin gene-related peptide upon bovine vascular endothelial and smooth muscle cells grown in isolation and co-culture. AB - 1. Bovine aortic endothelial cells (BAE) and smooth muscle cells (BASM) were grown separately and in co-culture. 2. Calcitonin gene-related peptide (CGRP) caused dose-dependent activation of adenylate cyclase in each cell type when grown in isolation. The concentration of CGRP causing half-maximal activation in BAE and BASM was 200 nM and 310 nM, respectively. 3. In cells grown in co-culture exposure to bradykinin produced dose-dependent elevations in cyclic GMP content which were maximal 1 min after application of the agonist. 4. CGRP (1 nM-1 microM) did not stimulate a rise in cyclic GMP in co-cultures. 5. Displaceable CGRP binding was identified throughout the wall of the bovine aorta. 6. We conclude that CGRP receptors coupled to adenylate cyclase are present on BAE and BASM, but there is no coupling of these receptors to the release of any agent (such as endothelium-derived relaxing factor) that activates guanylate cyclase. PMID- 2184912 TI - Mechanism of the potentiation of neurally-induced bronchoconstriction by gallamine in the guinea-pig. AB - 1. Electrical stimulation of the cervical vagi (15 Hz, 0.2 ms, 3 s, 7-15 V) produced a slight bronchoconstriction in the anaesthetized guinea-pig. This effect was fully abolished by atropine, while gallamine (0.1-10 mumol kg-1) produced a dose-dependent increase up to ten fold. 2. Gallamine-induced potentiation of neurally-mediated bronchoconstriction was not inhibited by depletion of sensory neuropeptides with capsaicin or by pretreatment with pyrilamine. In propranolol-pretreated guinea-pigs the potentiation induced by gallamine 3 and 10 mumol kg-1 was inhibited by 40 and 46%, respectively. 3. Physostigmine (0.5 mg kg-1) produced a very slight and slowly developing bronchoconstriction in the anaesthetized guinea-pig, which was also potentiated dose-dependently by gallamine (0.1-10 mumol kg-1). 4. Gallamine (10 mumol kg-1) potentiated the bronchial anaphylactic response induced by aerosol challenge with ovalbumin in actively sensitized guinea-pigs. 5. These results suggest that neither sensory neuropeptides nor histamine are involved in the gallamine-induced potentiation of neurally-mediated bronchoconstriction, while inhibition of the sympathetic nervous system may play a minor role. They are in general agreement with the hypothesis that gallamine antagonizes acetylcholine selectively at prejunctional muscarinic receptors in the guinea-pig airways, thus increasing its release from parasympathetic nerve terminals. These autoreceptors appear to be operant during anaphylactic bronchoconstriction. PMID- 2184914 TI - Recent advances in laboratory models for evaluation of helminth chemotherapy. AB - Extensive research on nematodes of veterinary importance has resulted in new tests based on incubation of parasitic nematodes in culture media, with a variety of detection systems including visual observation, inhibition of aggregation, reduced secretion of acetylcholinesterase and electronic motility measurements. There has been a proliferation of tests to detect benzimidazole resistant nematodes including egg embryonation, egg hatch, larval motility, differences in esterases, and tubulin binding by labelled benzimidazoles. A simple larval development test, which detects resistance to all types of anthelmintics, is likely to become the preferred test for evaluation of resistance in nematodes of grazing animals. By contrast the relative unimportance of trematodes and cestodes from a commercial point of view has resulted in few recent developments in models for evaluating chemotherapy. But the emergence of drug resistant strains of both schistosomes and liver fluke indicates the need for simple tests to detect resistance. PMID- 2184913 TI - The effect of diltiazem on the coronary haemodynamic and cardiac functional effects produced by intracoronary administration of endothelin-1 in the anaesthetized dog. AB - 1. We have studied the effect of the calcium channel antagonist, diltiazem, on the coronary haemodynamic and cardiac functional responses produced by intracoronary (i.c.) administration of endothelin-1 (ET-1) in anaesthetized dogs. 2. ET-1, 1, 3 and 10 ng kg-1 i.c., produced dose-related increases in coronary blood flow with no cardiac functional or systemic haemodynamic changes. ET-1, 30, 100 and 300 ng kg-1 i.c., produced dose-related reductions in coronary artery blood flow. The reduction in coronary blood flow was accompanied by dose-related falls in cardiac output, mean arterial pressure, +dP/dt and -dP/dt and increases in left ventricular end-diastolic pressure. However, there was no reflex tachycardia in response to the fall in blood pressure and at 300 ng kg-1, ET-1 produced a 22% reduction in heart rate. 3. Following a series of abnormal ECG changes, four out of five dogs died of ventricular fibrillation at 13 +/- 2 min after 300 ng kg-1 ET-1. 4. The administration of diltiazem (15 micrograms kg-1 min-1, i.v.) reduced mean arterial pressure by 10% and heart rate by 15%, and increased coronary blood flow by 39%. Diltiazem did not have any significant effect on the coronary dilator response to low doses of ET-1. Although there was a general trend for diltiazem to inhibit the coronary vasoconstrictor responses to ET-1, diltiazem significantly attenuated only the reduction in coronary blood flow produced by 100 ng kg-1 ET-1 by 60% but not the response to 30 or 300 ng kg 1 ET-1. Two out of five diltiazem-treated dogs died of ventricular fibrillation with a mean time to death of 20 min following treatment with ET-1 (300 kg- 1). 5. ET-1 is a very potent coronary vasodilator. At slightly higher doses ET-1 is also a coronary vasoconstrictor. ET-1 also appears to have direct cardiotoxicity independent of myocardial ischaemia. The vasoconstrictor activity and direct cardiotoxicity are only weakly inhibited by diltiazem. PMID- 2184915 TI - Down-regulation of angiotensin II receptors in subfornical organ of young male rats by chronic dietary sodium depletion. AB - The effect of a 4-week period of selective dietary sodium depletion on the regulation of peripheral and central angiotensin II receptors was studied in young rats, by quantitative autoradiography. Moderate sodium depletion (0.05% sodium in diet) significantly impaired growth rate and stimulated the renin angiotensin system, but did not result in significant changes in peripheral or central angiotensin II receptors. In young rats, the impairment of the growth rate and the stimulation of the peripheral renin-angiotensin system were more notable after profound sodium depletion (0.005% sodium in diet). Such sodium depletion corresponded to a down-regulation of kidney angiotensin II receptors, and to an up-regulation of adrenal zona glomerulosa angiotensin II receptors. These effects are similar to those reported in adult rats. In the brain, profound sodium depletion down-regulated angiotensin II receptors in the subfornical organ. There were no changes in angiotensin II receptors in another brain structure, the paraventricular nucleus. Our results indicate a participation of selective central angiotensin II receptors in the regulation of sodium metabolism and suggest that factors other than circulating angiotensin II levels might contribute to regulate the number of angiotensin II receptors in the subfornical organ. PMID- 2184916 TI - The role of surgery in the treatment of laryngeal cancer. PMID- 2184917 TI - Oral radiology in Canada. PMID- 2184918 TI - Retention and maintenance of fissure sealants over 10 years. AB - The long-term efficacy (retention and caries prevention) of fissure sealants is well documented. However, the effectiveness of contemporary sealants under sometimes less than ideal field conditions is not so well reported, nor are the clinical issues of the long-term extent of partial sealant loss, resealing needs and sealant replacement under such conditions. The results of a 10-year follow-up of 8,340 chemically-cured sealants placed between 1978 and 1985 in selected "high risk", first permanent molars of children of moderate to severe decay susceptibility are presented. These children were annual participants in the Prince Edward Island Children's Dental Care Program. Complete sealant retention was 89 per cent after one year and 60 per cent after 7-9 years. One year after insertion, 6 per cent of sealants required maintenance resealing; thereafter it was 2 per cent to 4 per cent per year. Sealant removals because of MO amalgam placement or occlusal decay were very low, about 2 per cent and 1 per cent, respectively, in each of the first five years. The overall annual sealant success of 96 per cent after one year and 85 per cent after 8-10 years supports the careful application of chemically-cured sealants under field conditions and the use of annual recalls to allow minimal sealant maintenance. PMID- 2184919 TI - A practical mouthstick for early intervention with quadriparetic patients. AB - There are few commercially available mouthsticks with bite plates that are easy to use by quadriparetic patients. The purpose was to design a practical, economical single-arch mouthstick for use in early rehabilitation. The mouthpiece designed was constructed out of self-curing acrylic. It adapted well to the existing dentition, hence giving a stable base. The mouthstick was easily fabricated, using limited materials and resources, and resulted in an appliance which was comfortable, required minimal training and allowed for independent use by the patient. PMID- 2184920 TI - Hypothesis: local vascular regulation is a key to flow limited muscle function. AB - The ability of canine oxidative skeletal muscle in situ to maintain developed isometric force is flow limited during twitch contractions at greater than 3 Hz. This limitation implies a mismatching of blood flow and the metabolic rate. The blood flow past a muscle cell is determined by the number of capillaries per fibre, the vascular conductance, the capillaries perfused and vascular autoregulation. Of these, capillary number is regulated on a time scale of days while the other three require seconds to minutes. Each of the regulatory systems involves hypoxia, adenosine and the eicosanoids as contributing factors which would predict that regulatory systems working on the same time scale should change in parallel. This does not appear to be the case at high metabolic rates. The resulting mismatching of flow and metabolism accelerates the fatigue process. This peripheral vascular limitation can exist without a central cardiovascular limit being reached. PMID- 2184921 TI - Clinical trials in the elderly. Pivotal points. AB - A clinical trial, that is, the scientific assessment of drug action in humans, must be undertaken only if there is reference to an expectation of benefit from the trial. Before the trial starts, a series of questions should be answered, including the need for the trial in elderly patients, particularly in view of the possible vulnerability of the elderly study subjects. Patient selection, randomization, follow-up, analysis, and interpretation must be scientifically valid. Of major importance is the external validity of the trial, that is, the generalizability. Any trial, particularly those involving the elderly, should be designed to develop or contribute to generalizable knowledge; that is, it should be possible to extend the conclusions from the trial beyond the study population to the population at large. When elderly are involved, as they should be when a drug is proposed for use mainly in the elderly population, it is especially important that the study be scientifically valid, medically important, and ethically sound. Studies involving the elderly should have sufficient numbers of females and minorities, the former because most elderly patients are females, the latter because minorities now reach the age of 65 years and beyond more so than in the past. Both risk and benefit should be addressed in terms of potential magnitude and duration. If the study drug has a narrow therapeutic window, it should be intensively studied. When the study is completed, there ought to be clear guidelines for the clinician to design initial, individualized, optimal dosage regimens or for subsequent adjustment of the regimen. The final report, which should be easily evaluable by clinicians, should fully discuss reasons for dropouts, inappropriate patient inclusion, number and types of adverse reactions, and defects in design and conduct of the study. PMID- 2184922 TI - Altered pharmacokinetics in the elderly. AB - Physiologic changes that occur in the aging process may directly affect drug pharmacokinetics. Alteration of the pharmacokinetics of these drugs in the elderly may necessitate adjustment of drug dosages to prevent toxicity or inadequate therapy. Whereas clinical tests to measure renal function may be used quantitatively to prospectively individualize a drug dosage to an elderly patient, tests for hepatic function do not correlate as well with changes in hepatic drug metabolism. Despite these limitations, recognition of the relationship between physiologic changes and drug pharmacokinetics is important to better prescribe the correct dose in the elderly population. PMID- 2184923 TI - Altered pharmacodynamics in the elderly. AB - The importance of age-related changes in drug sensitivity is increasingly appreciated. More conclusive evidence is now being presented in combined kinetic and dynamic studies. The type, intensity, and duration of drug action may be affected, ranging from therapeutic failure to major drug toxicity. Alterations in physiologic and homeostatic systems, including the autonomic system, baroreceptors, thermoregulation, and balance, have been described. These may explain the propensity to postural hypotension, falls, hypothermia, and confusion, particularly following drug-induced decrements in these systems. Studies on the sensitivity to individual drugs produce a varied picture emphasizing the danger of generalizations. An increased sensitivity to many agents affecting the central nervous system, including benzodiazepines, halothane, metoclopramide, and narcotic analgesics, is becoming apparent. For the latter this may also be accompanied by an age-associated qualitative difference in toxicity. Whereas there is conclusive evidence of a reduced responsiveness to propranolol, the data are conflicting for calcium antagonists. The increased hypotensive response to ACE inhibitors is more likely due to kinetic factors. The anticoagulant response to warfarin is enhanced. Evidence is also emerging of a wide divergence in the sensitivity of different systems to the same drug--with aging the inotropic effect of theophylline is increased, but the bronchodilator response is decreased. It is becoming clear also that there is a need to separately study certain subgroups of the elderly population. PMID- 2184924 TI - Altered pharmacodynamics of cardiovascular drugs and their relation to altered pharmacokinetics in elderly patients. AB - To properly predict drug effects in elderly patients for cardiovascular drugs requires understanding of age-related and disease-related changes in tissues and organs which mediate the observed pharmacodynamic response. Linking this understanding with the known changes in drug pharmacokinetics permits more effective cardiovascular pharmacotherapy in the geriatric patient. At the present time only a limited number of drug classes have been studied in this manner. Although it may be intuitively obvious that human pathophysiology may impact on drug response, until recently we have relied solely on description of drug concentration or pharmacokinetics to predict expected responses. We can look forward to improved geriatric therapeutics when the patient as well as the drug is considered as a variable in clinical therapeutic responses. PMID- 2184925 TI - Adverse drug effects. AB - Adverse drug effects afflict the elderly with greater frequency than the young. Several factors are responsible, among them the age-related alterations in pharmacokinetics and pharmacodynamics. Most importantly, it is the number of drugs taken on a daily basis that is cited as being the cause. When one extends the concept of adverse drug reactions to the concept of adverse drug events, then errors made by the patient, caregiver, and/or health care provider appear to be responsible to a large degree. PMID- 2184926 TI - Drug treatment and quality of life in the elderly. AB - The QL of patients on long-term pharmacologic treatment needs to be evaluated, especially in the elderly. This article discusses how this should be done and gives the results of studies on three groups of drugs commonly taken by elderly patients. Diuretic treatment does not appear to grossly impair QL, transdermal nitrates for angina do impair QL if used continuously, and tolerance limits their efficacy. Antihypertensive drugs appear to vary widely in their effects on QL. Drugs such as ACE inhibitors, verapamil, and atenolol appear preferable to the older drugs such as methyldopa and the beta-blocker propranolol, which have a central action. PMID- 2184927 TI - Geriatric nutrition. AB - The aging process alters body composition so that nutritional status changes as we get older. The aging process shows interindividual variability in its rate of development. Determinants of the rates of aging of systems and tissues are largely genetic. Premature aging of cells and tissues is due to genetic factors and to long-term exposure to physical or chemical environments that cause irreversible tissue damage. Whereas maximal lifespan is fixed for us all, individuals vary in life expectancy both because of variability in the risk of genetic disease which shortens life and because of variable capability for avoidance of those factors in our environment which cause early aging. Early aging as well as geriatric disease foreshorten life, but both can be prevented to some extent by diet or by diet and exercise. Diseases that can be nutritionally prevented, giving us a greater chance of achieving our genetically determined lifespans, include nutritional deficiency states and chronic diet-related diseases such as non-insulin-dependent diabetes, hypertension, coronary artery disease, and cancer. Disabilities resulting from these diseases and from degenerative arthritis are also subject to modulation by diet. The nutritional requirements of the elderly are mostly similar to those of younger people. Elderly usually need fewer calories and similar nutrient intakes compared with those of younger people. Elderly with higher needs for specific nutrients include homebound or institutionalized people who lack sunlight exposure and therefore require more vitamin D. Nutritional requirements to promote longer life expectancy and freedom from disabilities that result from chronic disease include restriction of food energy and fat. Nutritional assessment of the elderly is aimed at identifying not only the presence of deficiency states but also states of nutrient excess and chronic diet-related diseases. There are certain problems in carrying out nutritional assessment in the elderly, but techniques are now available which make valid assessment possible even in the oldest old. Those who live longest have less genetic risk of premature aging, but as a result of native intelligence, education, coping skills, and higher socioeconomic status, they also have a greater likelihood of eating a diet that best meets their long-term nutritional needs. Those most at risk for developing malnutrition as they get older are those who lack food access because of poverty, because of disability resulting from chronic geriatric disease, or because of a combination of these factors. Malnutrition is found in elderly in our society who live in their own homes if they are indigent, isolated, and homebound because of disability.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2184928 TI - Antihypertensive therapy in the elderly. AB - Recent studies have documented that arterial hypertension increases cardiovascular morbidity and mortality even in the geriatric population. Some elderly hypertensive patients, like younger patients, can benefit from antihypertensive therapy. Antihypertensive therapy should be carefully adjusted to suit the cardiovascular pathophysiology of elderly patients. PMID- 2184929 TI - Use of analgesics in the elderly. AB - Basic and clinical research on the pathophysiology, neurophysiology, biochemistry, and psychology of pain and its management has enhanced our understanding of this complex field. Clinical applications of new knowledge have led to the development of more effective analgesics and better modes of administration in concert with improved technology. However, applications to pain problems unique to the elderly require greater attention. Unfortunately, state-of the-art analgesic care is not widespread. Barriers exist in knowledge, skills, and attitudes among health care providers. To provide optimal analgesic care, management of each patient should be individualized. The prescribing of standard doses of analgesics should be condemned. An understanding of the various pain problems (acute and chronic) that afflict the elderly, the effects of aging on the pharmacokinetics and pharmacodynamics of analgesics, and the role of specific analgesics for specific pain states is necessary. In addition to analgesics, nonpharmacologic methods of pain control should be utilized. If needed, consultations or referrals to pain clinics or pain centers which provide expert evaluation, recommendations, and/or treatment are available. PMID- 2184930 TI - Nonsteroidal anti-inflammatory drugs. AB - Although the increased need for studies assessing the influence of age on the pharmacokinetics and pharmacodynamics of all drugs has been emphasized, relatively little is known about NSAIDs in the elderly. The pharmacokinetics of some NSAIDs have been examined in elderly subjects; unfortunately, recent data indicate that much of the earlier information may be incomplete or even misleading. Many studies report the disposition of only total NSAIDs. Since all of the NSAIDs are highly protein bound, it is the unbound, pharmacologically active, fraction that is most important. Few studies have quantified the pharmacokinetics of unbound NSAID in any age group, much less in elderly patients. Also, it is now apparent that studies of the propionic acid derivatives and other drugs with chiral centers must assess the disposition of the active S enantiomer. Finally, studies of NSAIDs that form acylglucuronides are confounded by the reversion of these metabolites to active drug. Reduced renal elimination of these metabolites may be greater in elderly persons. Studies that account for these features of NSAIDs will provide necessary data for safe and effective use of NSAIDs in the elderly. PMID- 2184931 TI - Antidepressants. AB - Depressive symptoms are common in the elderly, and depressive illness is the most common of emotional disorders in those of advanced age. This article focuses on the use of antidepressant drugs for the treatment of older depressed patients. To correctly understand the use of antidepressant drugs, it is necessary to first appreciate the medical, neurobiologic, and pharmacologic context within which antidepressant drugs are to be prescribed. Therefore, this article also includes a brief review of the etiology and diagnosis of depression in the elderly. PMID- 2184932 TI - Alternate drugs. AB - It is important to consider a number of factors when deciding on drug therapy for elderly patients. The principles of efficacy, side effect profile, ease of administration, interaction with other drugs or concomitant illness, cost, and constant reevaluation of the need for continued treatment should be remembered for any treatment. In many cases the ideal drug may be initially no drug at all. A number of alternative drugs are available for most conditions, and the drug of choice for the elderly may actually be one of these alternative agents. We have attempted to consider these basic principles as they may be applied in making a decision for ideal drug therapy and for alternative therapies for elderly patients. PMID- 2184933 TI - Cancer predisposition of ataxia-telangiectasia heterozygotes. AB - Ataxia-telangiectasia (A-T) is a progressive neurologic disorder in which there is varied immune dysfunction, an excess sensitivity to ionizing radiation, and a striking predisposition to cancer. It is the autosomal recessive syndrome for which there is the strongest evidence, derived from retrospective studies of cancer incidence and mortality in A-T families, that the heterozygote is predisposed to cancer. We present, in tabular form, the specific cancer sites or types most likely to be associated with A-T heterozygosity. These include solid tumors of the breast, pancreas, stomach, bladder, and ovary, and chronic lymphocytic leukemia. We also introduce a new method to test these associations. As soon as molecular probes for the A-T allele(s) are available, this new research design will be used to test rigorously each association, hypothesized on the basis of previous data, between a specific cancer site and A-T heterozygosity. PMID- 2184934 TI - Cancer in ataxia-telangiectasia patients. AB - A gene locus for ataxia-telangiectasia (A-T) is in chromosome region 11q22 to 11q23 and predisposes to cancer. Ataxia-telangiectasia patients appear to have two separate clinical patterns of malignancy. One pattern involves solid tumors, which have not been stressed and which include malignancies in the oral cavity, breast, stomach, pancreas, ovary, and bladder. Detection of a solid tumor in an A T patient should serve as a warning. It heralds a markedly elevated risk of another malignancy in that patient. The second pattern of neoplasia in A-T is well recognized and consists of lymphocytic leukemia and non-Hodgkin's lymphoma. These malignancies may relate to immunodeficiency in A-T and to chromosome breakage and rearrangement, which are a feature of A-T. These two patterns of malignancy may be truly separate and reflect different mechanisms of malignancy in A-T, or they may not really be separate but instead reflect a single mechanism of malignancy. The situation in A-T is reminiscent of that in the acquired immunodeficiency syndrome (AIDS), in which Kaposi's sarcoma occurs with mild immunodeficiency and pneumocystis carinii pneumonia occurs with more profound immunodeficiency owing to the human immunodeficiency virus. Next to pulmonary disease, cancer is the leading cause of death in A-T. PMID- 2184935 TI - [Directiones ad rem medicam pertinentes. On the medical manuscripts of G.W. Leibnitz from approximately 1680]. PMID- 2184936 TI - [The importance of C-peptide determination in the treatment and prognosis of type II diabetes]. AB - The concentration of C peptide which is an indicator of the secretory capacity of the beta-cells of the pancreas was assessed in 109 patients with type II diabetes, hospitalized on account of prolonged difficulties as regards compensation. The values on fasting, the maximal values after stimulation following an experimental meal and increments were greater than in age- and weight-matched controls. In diabetic patients some highly significant relationships were revealed between the C peptide concentration on fasting and indicators of the risk of ischaemic heart disease [IHD]. They included HDL cholesterol, the body mass index and uric acid. The relationship between the maximal C peptide concentration and serum sodium may be associated with a greater disposition for hypertension. Thirty-one patients with symptoms of an ischaemic myocardial lesion had a significantly elevated C peptide concentration on fasting. The increments of C peptide concentration after an alimentary stimulus correlated indirectly with indicators of the actual and long-term compensation of diabetes. In relation to the reduced increments also the need of insulin therapy was reflected. Data obtained by examination of the C peptide concentration in the blood of type II diabetics can contribute to the objectivization of needs of insulin treatment and to the detection of the link between cardiovascular risk and hyperinulinaemia. PMID- 2184937 TI - [Medical bookplates]. PMID- 2184938 TI - [Captopril in the therapy of stable angina pectoris]. AB - In 28 patients with chronic angina pectoris grade II-III (NYHA) the authors investigated the antianginous effect of captopril. All patients had a normal blood pressure and the diagnosis was confirmed by coronary angiography. The investigation was made in three sub-groups as a simple crossover experiment with a randomized onset. In 10 patients without dysfunction (group A) and eight with severe left ventricular dysfunction (group C) a short-term comparative study of captopril and placebo was made; 10 patients of group B took first for 7 days diltiazem, 3 X 60 mg, and then during subsequent weeks the action of diltiazem with placebo was compared and the action of diltiazem combined with captopril 3 X 25 mg per day. Captopril significantly reduced the blood pressure and Robinson's index at rest and during activity. It protracted significantly the time before the development of stenocardia in patients with left ventricular dysfunction and in the group treated with diltiazem where it reduced even further the incidence of stenocardias. ACE inhibitors may apparently enhance the effectiveness of diltiazem in normotensive patients with angina pectoris and it may be assumed that it will have an even more potent effect in concurrent hypertension or left ventricular dysfunction. PMID- 2184939 TI - [New findings about the youthful years of Vaclav Treitz]. PMID- 2184940 TI - The involvement of calcium in transport of secretory proteins from the endoplasmic reticulum. PMID- 2184941 TI - Purified human I kappa B can rapidly dissociate the complex of the NF-kappa B transcription factor with its cognate DNA. AB - I kappa B is an inhibitory protein that stabilizes the inducible cytoplasmic form of the NF-kappa B transcription factor. We have purified I kappa B-alpha, a major form of I kappa B with an apparent molecular size of 37 kd, from cytosol of human placenta. A second chromatographically distinct form, I kappa B-beta, was partially purified and found to be more basic and 3-8 kd larger than the alpha form. The occurrence of distinct forms of I kappa B could explain how NF-kappa B can be activated in response to various agents that signal via different intracellular messenger systems. Both I kappa B-alpha and -beta exclusively inactivated NF-kappa B containing the non-DNA binding 65 kd subunit and, within minutes, could dissociate a high affinity complex of NF-kappa B with its cognate DNA. On the assumption that free I kappa B-alpha and -beta can enter the nucleus, these proteins could rapidly release NF-kappa B from high affinity binding sites in enhancer and promoter elements, thereby terminating NF-kappa B-dependent initiation of gene expression. PMID- 2184942 TI - Cloning and characterization of CAP, the S. cerevisiae gene encoding the 70 kd adenylyl cyclase-associated protein. AB - Adenylyl cyclase from S. cerevisiae contains at least two subunits, a 200 kd catalytic subunit and a subunit with an apparent molecular size of 70 kd, which we now call CAP (cyclase-associated protein). We cloned a cDNA encoding CAP by screening a yeast cDNA expression library in E. coli with antisera raised against the purified protein. The cDNA contained an open reading frame capable of encoding a 526 amino acid protein that is not homologous to any sequences in the current data bases. Adenylyl cyclase activity in membranes from cells that lacked CAP was not stimulated by RAS2 proteins in vitro. These results suggest that CAP is required for at least some aspects of the RAS-responsive signaling system. Mutants lacking CAP had four additional phenotypes that appear to be unrelated to effects of the RAS/adenylyl cyclase pathway: the inability to grow on rich medium (YPD), temperature sensitivity on minimal medium, sensitivity to nitrogen starvation, and a swollen cell morphology. PMID- 2184943 TI - [The history of medicine in Czechoslovakia]. AB - The author analyzes the role of history of medicine in Czechoslovakia. Based on its past and present state, perspectives of its further development are outlined. The author emphasizes the role of its founders and creators (Schrutz, Spilka, Matousek, Sinkulova). He has a critical attitude to the present state which does not correspond to the possible role of history of medicine. Suggestions and tasks as well as their implementation are outlined: in particular effective organizational collaboration, a defined place among other scientific disciplines, integrated research, training at medical faculties and schools for health workers and a creative, active function in the thinking and recognition of health workers. PMID- 2184944 TI - Evolving concepts in the management of congenital junctional ectopic tachycardia. A multicenter study. AB - We reviewed the records of 26 infants with congenital junctional ectopic tachycardia (JET) from seven institutions to examine the evolution in the management of this tachycardia that is difficult to treat. JET was defined electrocardiographically as an incessant tachycardia with normal QRS morphology and atrioventricular (AV) dissociation. The ventricular rate ranged from 140 to 370 beats/min (mean, 230 beats/min); 16 of 26 patients had cardiac failure. Treatment success was defined as a stable decrease in the rate of JET, below 150 beats/min; partial success was a significant decrease of JET rate with alleviation of symptoms. All patients received digoxin with no significant effect. Propranolol was given to 16 patients, with two successes and one partial success. Combinations of other conventional agents were used in 11 patients with two successes; 14 patients were treated with amiodarone, which resulted in eight successes and three partial successes; three patients died suddenly on medical treatment (amiodarone, one patient; propranolol, one patient; or amiodarone plus propranolol, one patient); sudden AV block was a possible cause and consequently, two later patients had pacemaker implantation as well as medical treatment. His catheter ablation was successfully performed twice but contributed to death in a newborn; three surgical His ablations were performed for intractable JET with two successes and one death. The overall mortality was 35%. Among survivors, treatment has been stopped without any complications in five patients ranging in age from 10 months to 8 years (mean, 3.5 years). It seems that amiodarone alone is the best drug for treatment of congenital JET; necessity for permanent pacing remains unsettled. His ablation should be reserved only for intractable JET. PMID- 2184945 TI - Controlled trial of aerobic exercise in hypertension. AB - To determine the antihypertensive efficacy of aerobic exercise training in mild essential hypertension, a prospective randomized controlled trial was conducted comparing an aerobic exercise regimen to a placebo exercise regimen, with a crossover replication of the aerobic regimen in the placebo exercise group. The study took place in an outpatient research clinic in a university-affiliated Veterans Administration medical center. Twenty-seven men with untreated diastolic blood pressure (DBP) of 90-104 mm Hg were randomized to the two exercise regimens. Ten patients completed the aerobic regimen. Nine patients completed the control regimen, seven of whom subsequently entered and completed the aerobic regimen. The aerobic regimen consisted of walking, jogging, stationary bicycling, or any combination of these activities for 30 minutes, four times a week, at 65 80% maximal heart rate. The control regimen consisted of slow calisthenics and stretching for the same duration and frequency but maintaining less than 60% maximal heart rate. DBP decreased 9.6 +/- 4.7 mm Hg in the aerobic exercise group but increased 0.8 +/- 6.2 mm Hg in the placebo control exercise group (p = 0.02). Systolic blood pressure (SBP) decreased 6.4 +/- 9.1 mm Hg in the aerobic group and increased 0.9 +/- 9.7 mm Hg in the control group (p = 0.11). Subsequently, seven of the nine controls entered a treatment crossover and completed the aerobic regimen with significant reductions in both DBP (-6.1 +/- 3.2 mm Hg, p less than 0.01) and SBP (-8.1 +/- 5.7 mm Hg, p less than 0.01). BP changes were not associated with any significant changes in weight, body fat, urinary electrolytes, or resting heart rate. This randomized controlled trial provides evidence for the independent BP lowering effect of aerobic exercise in unmedicated mildly hypertensive men. PMID- 2184946 TI - Coronary artery imaging with intravascular high-frequency ultrasound. AB - Safe and effective clinical application of new interventional therapies may require more precise imaging of atherosclerotic coronary arteries. To determine the reliability of catheter-based intravascular ultrasound as an imaging modality, a miniaturized prototype ultrasound system (1-mm transducer; center frequency, 25 MHz) was used to acquire two-dimensional, cross-sectional images in 21 human coronary arteries from 13 patients studied at necropsy who had moderate to-severe atherosclerosis. Fifty-four atherosclerotic sites imagined by ultrasound were compared with formalin-fixed and fresh histological sections of the coronary arteries with a digital video planimetry system. Ultrasound and histological measurements correlated significantly (all p less than 0.0001) for coronary artery cross-sectional area (r = 0.94), residual lumen cross-sectional area (r = 0.85), percent cross-sectional area (r = 0.84), and linear wall thickness (plaque and media) measured at 0 degrees, 90 degrees, 180 degrees, and 270 degrees (r = 0.92). Moreover, ultrasound accurately predicted histological plaque composition in 96% of cases. Anatomic features of the coronary arteries that were easily discernible were the lumen-plaque and media-adventitia interfaces, very bright echoes casting acoustic shadows in calcified plaques, bright and homogeneous echoes in fibrous plaques, and relatively echo-lucent images in lipid-filled lesions. These data indicate that intravascular ultrasound provides accurate image characterization of the artery lumen and wall geometry as well as the presence, distribution, and histological type of atherosclerotic plaque. Thus, ultrasound imaging appears to have great potential application for enhanced diagnosis of coronary atherosclerosis and may serve to guide new catheter-based techniques in the treatment of coronary artery disease. PMID- 2184948 TI - Physical activity and children. PMID- 2184947 TI - Effects of insulin on vasoconstriction induced by thromboxane A2 in porcine coronary artery. AB - To elucidate the role of insulin in the control of coronary artery tone, its effects on porcine coronary artery contraction evoked by thromboxane A2 (TXA2) were studied in vitro. Ring preparations of porcine proximal coronary artery were suspended in a Magnus apparatus filled with Tyrode's solution at 37 degrees C and aerated with 100% O2, and the isometric tension of the contractions was measured. Insulin itself caused neither contraction nor relaxation. Insulin had no significant effect on the coronary artery contractions evoked by 20 mM K+, norepinephrine, histamine, and serotonin; however, 120 minutes of preincubation with a physiological concentration of insulin (30-300 muunits/ml) significantly accentuated coronary artery contractions evoked by STA2 (10(-11) to 10(-7) M), a stable analogue of TXA2 that is known to act on TXA2/prostaglandin H2 receptors (141.4 +/- 10.9% of the control at 10(-7) M STA2 in the presence of 300 muunits/ml insulin; p less than 0.01). The enhancing effects of insulin on the STA2-induced contractions were affected by extracellular glucose or magnesium ion concentrations. The enhancing effects of insulin were observed only at the glucose concentrations of 100-300 mg/dl and magnesium concentrations of 0.5-1.5 mM. Therefore, insulin was suspected of enhancing TXA2-induced contraction through a process that depends on extracellular glucose and Mg2+. PMID- 2184949 TI - Evolving concepts in the management of congenital junctional ectopic tachycardia. PMID- 2184950 TI - Intravascular ultrasound. Looking below the surface of vascular disease. PMID- 2184951 TI - The cholesterol facts. A summary of the evidence relating dietary fats, serum cholesterol, and coronary heart disease. A joint statement by the American Heart Association and the National Heart, Lung, and Blood Institute. The Task Force on Cholesterol Issues, American Heart Association. PMID- 2184952 TI - The measurement of circulating parathyroid hormone. AB - Until recently, the measurement of circulating parathyroid hormone (PTH) has been unsatisfactory due to poor analytical performance of immunological assays and due to interference in such assays by circulating biologically inactive fragments of PTH. The development of a two-site immunometric assay with the use of acridinium ester as label has solved these problems. This immunochemiluminometric assay (ICMA) measures the intact molecule and is capable of detecting PTH levels in normal subjects as well as suppression of PTH after oral administration of calcium. The ICMA PTH assay has been shown to be adequate in the diagnosis of primary hyperparathyroidism and it could prove useful in monitoring renal failure patients and investigating other bone diseases such as osteoporosis. PMID- 2184953 TI - The assessment of pituitary function. AB - The assessment of pituitary function can now be carried out quickly and accurately by means of outpatient testing procedures and hormone immunoassays. Improvements in assay methodology have resulted in greater specificity and sensitivity although some technical problems remain. The diagnosis of patients with functioning and nonfunctioning pituitary tumors, hypopituitarism and target gland disorders is discussed with particular reference to diagnostic difficulties and recent advances. PMID- 2184954 TI - Calcium homeostasis. AB - The regulation of plasma calcium concentration and bone homeostasis is briefly described. The components of plasma calcium and the method for deriving these components are presented. The factors which regulate plasma calcium concentration are discussed with particular reference to the role of the kidney. The mechanisms responsible for the maintenance of the skeleton are described and the failure of these mechanisms in the pathogenesis of osteoporosis is outlined. In postmenopausal women there is increased excretion of calcium and recent works suggest that this is due to an increase in the complexed fraction of calcium as a result of an increase in plasma bicarbonate and anion gap. The significance of the increase in urine calcium excretion in postmenopausal women and its impact on dietary calcium requirement are discussed. PMID- 2184955 TI - The role of receptor kinase in insulin action and the effects of insulin on human hepatoma cells. AB - Insulin has both short- and long-term effects on cellular metabolism. The short term effects are known to involve the insulin receptor, a protein kinase capable of phosphorylating itself and other proteins. The role of the receptor was elucidated by studies of a mutant insulin receptor which lacked kinase activity and inhibited several actions of insulin. The long-term effects of insulin could be demonstrated by its growth-promoting effect on hepatoma cells, and by the suppression in transfected hepatoma cells of hepatitis B virus antigen production in a dose-dependent manner. The process whereby insulin appears to regulate gene expression is not clearly understood. PMID- 2184956 TI - Assessment of renal function: selected developments. AB - Tests commonly used to assess the glomerular filtration rate (GFR) and to detect renal tubular damage are critically reviewed. Creatinine clearance which is frequently used for assessment of the GFR is prone to several errors. The plasma creatinine can be used to provide a rough guide but for reliable measurement of the GFR, 51Cr-EDTA clearance is recommended. Measurements of the urinary excretion of low molecular weight proteins, enzymes and kidney tissue proteins have been used to detect tubular damage. Of the low molecular weight proteins excreted, beta-2-microglobulin is unstable and measurement of retinol-binding protein or alpha-1-microglobulin is recommended for the detection of chronic renal tubular malfunction. Of the many enzymes that have been studied, urinary N acetyl-beta-D-glucosaminidase or alanine aminopeptidase are recommended as being the most useful for the early detection of acute renal tubular damage. Among renal tissue proteins that have been measured in urine adenosine-deaminase binding protein, a tubular brush border antigen appears to have considerable potential for providing early warning of renal allograft rejection. PMID- 2184958 TI - Lipid metabolism in renal failure. AB - Many patients with renal failure show abnormalities of lipid metabolism. Hypertriglyceridemia and low levels of high density lipoprotein (HDL) cholesterol are frequent abnormalities in uremic patients. The hypertriglyceridemia and low HDL cholesterol are thought to result from decreased lipoprotein lipase activity. The decreased levels of hepatic lipase observed in renal failure may account for the presence of intermediate density lipoproteins (IDL) and the high HDL2 subfraction. The risk factor for coronary artery disease expressed as the ratio of total cholesterol to HDL cholesterol is elevated in renal failure patients, especially in those with hypertriglyceridemia. Treatment of renal patients with gemfibrozil partially reverses many of the lipid abnormalities including the low HDL cholesterol. However, only the HDL3 subfraction increased while HDL2 remained unchanged. PMID- 2184957 TI - Effects of renal failure. AB - The multiple features of the syndrome of uremia are a result of the retention of a wide variety of metabolic end products. Although a number of metabolites have been incriminated as "the uremic toxin," none of them accounts for all aspects of uremia. It is likely that the uremic syndrome is a result of the pathological effects of many retained substances. Of major current interest is the development of toxicity in brain, bone and other tissues due to accumulation of aluminum. The recognition of aluminum toxicity may have implications not only in patients with impaired renal function but also in other disease states. PMID- 2184959 TI - Nitrosamines as potential environmental carcinogens in man. AB - Nitrosamines are ubiquitous in our environment and diet. Many nitroso compounds are carcinogenic in animals and most probably in man. Nitrosamines are formed from the reaction of nitrite with primary, secondary, or tertiary amines in an acid medium. Nitrate should be considered as a nitrosating agent because it can be converted to nitrite by microbial action. Many aliphatic and nitrogen containing heterocyclic compounds can be nitrosated to form carcinogenic substances. The occurrence in food and in some drugs of several nitrosamines or their nitrosatable precursors is described. Several tobacco-specific nitrosamines have been considered as possible causative agents for human cancer. Nitrosamines may be implicated in the induction of certain human gastric cancers. PMID- 2184960 TI - Toxic risks of inappropriate therapy. AB - Drug therapy may produce toxicity. Patient individuality or drug interactions account for many cases of poisoning, but other factors such as genetic predisposition, drug contamination or human error are also known causes. Examples of various types of drug poisoning are given, illustrating the role of the clinical chemist in minimizing or studying drug toxicity. PMID- 2184961 TI - A preliminary report on the role of somatostatin analogue (SMS 201-995) in the management of children with tall stature. AB - We have studied the effect of somatostatin analogue (SMS 201-995) given as a subcutaneous injection on the growth and growth hormone secretion in seven tall children (two male; five female). SMS 201-995 was given in doses of 37.5 or 50 micrograms on a once or twice-daily regimen. Growth velocity decreased from a pretreatment median of 8.3 cm/year (range 5.5-12.2) to 3.0 cm/year (range 0.2 4.5) after 6 months treatment (Wilcoxon, P = 0.02). In three of the children therapy was discontinued for the next 6 months with restoration of growth rate to pretreatment values in two of the three. Growth hormone secretion decreased as a result of SMS 201-995 therapy although one child needed a twice-daily regimen to achieve long-term suppression. Final height measurements were reduced in four of five patients with an overall reduction between 1.1 and 6.3 cm and no change in the other. No effects of treatment on fasting glucose and insulin, glycosylated haemoglobin or serum thyroxine concentrations were observed. These preliminary studies suggest that SMS 201-995 may have a role in the management of the growth of tall children but the optimum mode of administration remains to be established. PMID- 2184962 TI - [A manifesting carrier of Duchenne muscular dystrophy presenting mosaic distribution of dystrophin negative and positive muscle fibers]. AB - A 25-year-old female patient with an approximate 10-year-history of slowly progressive muscle weakness was diagnosed as a manifesting carrier of Duchenne muscular dystrophy (DMD) because her muscle biopsy showed scattered fibers with no dystrophin on immunohistochemical staining. She had no family history of neuromuscular disorders. She was in good health until about 14 years of age, when she developed muscle weakness and atrophy of the extremities with slow aggravation. On admission at the age of 25 years, she had asymmetrical muscle atrophy in the lower extremities; the left femur, right femur, left crus, and right crus measured 36.0, 40.5, 31.5, and 35.5 cm in circumference, respectively. However, the muscle weakness of the extremities was symmetrical with no laterality, and the proximal muscles in the lower extremities were predominantly affected to 3+/5 MMT test. She walked with a mild wadding manner and stood up with Gower' maneuver. Deep tendon reflexes of the extremities were almost normoactive with no pathologic reflexes. As to laboratory findings, serum enzymes of muscular origin were elevated; GOT was 44 IU/l, GPT 60 IU/l, LDH 829 IU/l, CK 4238 IU/l, and aldolase 31 SL units. The electromyogram showed myopathic changes mixed with some neurogenic components. Peripheral nerve conduction velocity was normal. A computed tomography of the skeletal muscles showed more marked atrophy and lower density in the left lower extremity than in the right. The biopsied left gastrocnemius muscle demonstrated a marked variation in fiber size with some necrotic and regenerating fibers. On immunohistochemical stain with anti dystrophin antibody, the dystrophin negative fibers were scattered among positive fibers in a mosaic distribution. PMID- 2184963 TI - [Oculopharyngeal muscular dystrophy in a Japanese family]. AB - The first instance of familial oculopharyngeal muscular dystrophy (OPMD) affecting a Japanese family is reported. Three patients (a 62-year-old female, her sisters 66-year-old and 53-year-old) were described with suspicious other 2 cases. A 62-year-old woman (case 1) developed bilateral blepharoptosis at the age of 52. Then she became aware of difficulty in swallowing solid foods, had developed a nasal voice and aspiration of liquids. On admission, neurological examination revealed moderate bilateral blepharoptosis, nasal voice, dysphagia and hyporeflexia of the pharynx. There was mild weakness of the muscles of the temporalis, masseter, face, neck and proximal portions of the upper limbs. The levels of serum creatine phosphokinase, lactic acid and pyruvic acid were normal. Tensilon test was negative. The needle EMG showed a myogenic pattern with no waning phenomenon. Nasopharyngeal fiberscopy, laryngoscopy, esophageal fluoroscopy and hydrodynamic examination showed dyskinesis of the soft palate, retention of saliva in recessus piriformis and streaming into the larynx. Cricopharyngeal myotomy was performed for the purpose of relieving the dysphagia. The muscles were obtained from cricopharyngeus of both sides during surgery, and right deltoid muscle in biopsy. The muscles of sternohyoideus and deltoideus showed myogenic changes, and some fibers with rimmed vacuoles especially in small angulated fibers under the light microscope. Whereas the crycopharyngeus showed dystrophic change, which was apparent in the right side. There were also nemaline rods found in a few fibers undergoing necrosis. ATPase preparations revealed type 1 predominant in cricopharyngeus and type 2 predominant in sternohyoideus. Most atrophic fibers were in type 1 fibers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2184964 TI - [A case of polymyositis associated with chronic active hepatitis]. AB - A case of polymyositis associated with chronic active hepatitis was reported. A 53-year-old man, who had no previous history of blood transfusion nor hepatitis, noticed proximal dominant muscle weakness on January 29, 1985. He was admitted to Kyoto National Hospital on February 7, and laboratory studies disclosed the elevation of serum enzyme levels; creatine kinase (CK) 9845 IU/L (normal 54-263), glutamate oxaloacetate transaminase (GOT) 834 IU/L (9-31), glutamate pyruvate transaminase (GPT) 491 IU/L (4-34), lactate dehydrogenase (LDH) 2135 IU/L (248 464). Also serum gamma globulin was high (1.8 g/dl) and LE-like cell was found. The diagnosis of polymyositis was made and prednisolone therapy (60 mg/day) was started on February 23. The elevated serum enzymes decreased gradually, but severe muscle weakness persisted for about one month. On April 3, he was admitted to our hospital. Physical examination revealed moderate proximal dominant muscle weakness without skin eruption, jaundice or hepatosplenomegaly. The serum enzymes were still high; CK 1826, GOT 173, GPT 232 (GOT less than GPT), LDH 1548. However, alkaline phosphatase (ALP) and bilirubin were normal. Hepatitis B surface antigen (HBsAg) was not detected. Antinuclear antibody was positive. The electromyogram study showed myopathic change, and the muscle biopsy demonstrated myopathic change and cell infiltration, compatible with polymyositis. These results suggested liver dysfunction associated with polymyositis. Prednisolone therapy was continued and muscle weakness decreased. From December, 1985, serum enzymes (CK, GOT, GPT, LDH) elevated again and muscle weakness also slightly increased. Anti-smooth muscle antibody was positive. It was suggested that both polymyositis and liver dysfunction deteriorated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2184965 TI - [Medial medullary infarction demonstrated by MRI]. AB - A 67-year-old woman with medial medullary infarction is reported, including clinical manifestations, MRI and angiographical findings, and results of evoked potentials. She suffered from contralateral hemiplegia and disturbance of deep sensation. Motor paresis of the tongue was absent. Magnetic resonance imaging revealed a lesion in the medial portion of the medulla oblongata. The 17 cases previously reported with medial medullary infarction are reviewed. Only 3 cases had triad of medial medullary infarction, contralateral hemiparesis, deep sensory disturbance, and ipsilateral hypoglossal paresis. Therefore, lesion detection is necessary to diagnose medial medullary infarction. Most infarctions limited to the upper third of the medulla were caused by occlusions of vertebral arteries or their branches and prognosis was good. In contrast, infarctions in the lower two thirds were caused by occlusions of anterior spinal arteries and their branches and the prognosis was poor. Thus localization of the lesion using MRI plays an important role to predict the prognosis. PMID- 2184966 TI - [Motor amusia following a right temporal lobe hemorrhage--a case report]. AB - A 65-year-old female was admitted to our hospital because of left hemiparesis with sudden onset one week before. She was congenitally right-handed. She had been a teacher of Japanese string instrument (samisen) playing and been able to sing Japanese traditional songs well. A tape on which she had recorded her songs one year before the admission also proved her to be a good singer. Neurological examination on admission revealed almost normal findings except for minimal weakness in her left hand fingers. Right temporal lobe hemorrhage was revealed by CT scan. One month after the admission, she complained that she was unable to sing her songs and to play samisen as she used to do. Her intelligence was normal (WAIS VIQ116, PIQ108) and there were no abnormal findings as follows: aprosodia, aphasia, agraphia, memory disturbance, agnosia and ideational, ideomotor, constructional or limb-kinetic apraxia. She could point out her errors while singing. However, musical receptive function was slightly disturbed with tonal memory in Seashore test. When she was asked to sing a song without any instrumental support, she hummed a melody occasionally with wrong pitch, but rhythmically. After hearing a song she knew well, she reproduced it with slight improvement. With the vocal or the instrumental accompaniment, she could sing fairly well. She had some mistakes of pitch while playing a samisen. MRI was performed one year and a half after the brain hemorrhage. It displayed a thin linear of hematoma in the white matter of the right upper temporal and transverse gyrus. It was proved in our case that motor amusia with minimal musical receptive dysfunction could appear following a cerebral lesion and musical function might be independent of intelligence or verbal function. PMID- 2184967 TI - Public Law 99-457 and the clinical pediatrician. Part 2: Implication for the pediatrician. AB - This is the second of a 2-part presentation of the requirements and the implications for the pediatrician of Federal Law PL 99-457. Part 1, printed in March 1990, defined the details of the law. PMID- 2184968 TI - Spinal dysraphism: use of magnetic resonance imaging in evaluation. AB - Three cases of children with spinal dysraphism are reported. Magnetic resonance imaging (MRI) was used as a primary diagnostic examination. The ages of the patients were 2 days, 4 years, and 16 years. In all instances the scan gave a precise diagnosis as well as well as an accurate delineation of the structural abnormalities before surgical treatment. Plain radiographs and ultrasound analysis may not be helpful, and invasive procedures can be associated with morbidity. Technical ease, safety, and anatomic precision suggest that MRI should be performed as a primary radiologic examination in the diagnostic workup of spinal dysraphism. PMID- 2184969 TI - The Schinzel-Giedion syndrome. A case report and review of the literature. AB - The authors discuss a 1-day-old boy who had Schinzel-Giedion syndrome. This is the fifth case reported in the literature, and it presents additional abnormalities that have not been reported previously. The Schinzel-Giedion syndrome includes facially dysmorphic, skeletal, cardiac, and genito-urinary anomalies, but mainly congenital hydronephrosis. The diagnosis can be made by clinical and radiological examinations. PMID- 2184970 TI - Concurrent care: a page from the Medicare carriers manual. PMID- 2184971 TI - Adenosine in the episodic treatment of paroxysmal supraventricular tachycardia. AB - The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of adenosine in the treatment of episodes of paroxysmal supraventricular trachycardia (PSVT) are reviewed. Adenosine is an endogenous adenine nucleoside that markedly decreases heart rate and prolongs atrioventricular (AV)-nodal conduction. Adenosine is rapidly cleared from plasma by the cellular elements of the blood and by vascular endothelial cells and subjected to enzymatic metabolism. The drug has a half-life of 0.6 to 10 seconds. In noncomparative clinical trials, adenosine terminated 85% to 100% of induced or spontaneous episodes of PSVT involving the AV node in the reentrant circuit. In patients with arrhythmias that do not involve the AV node in the reentrant circuit, adenosine produces AV block and does not restore sinus rhythm. Prospective, randomized trials comparing adenosine with verapamil in adults have not yet been performed. The adverse effects of adenosine include flushing, dyspnea, headache, cough, chest pain, sinus bradycardia, atrial fibrillation, ventricular arrhythmias, and various degrees of AV block. Because of the short half-life of adenosine, these effects are transient and well tolerated. The initial dose of adenosine in treating acute PSVT is 6 mg given by rapid i.v. bolus injection, followed in one to two minutes by up to two additional 12-mg boluses if necessary. Adenosine has been found to be effective in terminating PSVT and thus offers an alternative to verapamil. Prospective, randomized trials comparing adenosine with verapamil are needed to definitively establish adenosine's role in the therapy of PSVT. PMID- 2184972 TI - Adenosine: supplementary considerations about activity and use. PMID- 2184973 TI - Treatment of pelvic inflammatory disease. AB - The pathogenesis, risk factors, microbiology, sequelae, diagnosis, and treatment of pelvic inflammatory disease (PID) are reviewed, and factors associated with the selection of effective, safe, and economical drug therapy are discussed. PID is an acute clinical syndrome not related to surgery or pregnancy that is caused by the spread of microorganisms from the vagina and cervix to the endometrium, fallopian tubes, and other adnexal structures. Primary PID, the most common form of the disease, is the result of the ascent of sexually acquired or endogenous lower genital tract microorganisms to the upper genital tract. Presence of a sexually transmitted disease is the most common risk factor for PID, but a previous episode of PID, multiple sexual partners, intrauterine device use, and young age are also risk factors. PID is classified as gonococcal or nongonococcal (i.e., caused by anaerobic and aerobic pelvic organisms). The long-term consequences of PID are the most devastating aspects of the disease; infertility remains the most common sequela. Therapy of PID is aimed at preserving fertility, preventing long-term consequences, and relieving acute clinical symptoms. In areas in which penicillinase-producing Neisseria gonorrhoeae is endemic, therapy that is effective against penicillinase-producing N. gonorrhoeae is necessary. Gonococcal PID that is not penicillin resistant may be treated with a single intramuscular or oral dose of a penicillin; penicillin-resistant infection may be treated with a cephalosporin or ciprofloxacin. If chlamydia is a diagnostic consideration, a one- to two-week course of oral tetracycline or doxycycline (injectable-drug therapy is an alternative) should be added to the regimen. Single-agent therapy is a cost-effective alternative to combination regimens. Ampicillin-sulbactam is a cost-effective alternative to the more costly injectable cephalosporins or the combination regimens of an aminoglycoside plus clindamycin or metronidazole. With the increasing prevalence of PID in the United States, the selection of cost-effective antimicrobial therapy has important implications for the hospital pharmacist and the pharmacy and therapeutics committee. PMID- 2184974 TI - Tumor markers in gynecologic neoplasms. AB - The applications of tumor markers and steroid receptors in gynecologic neoplasms are described. The value of immunohistologic techniques in the histogenetic assessment of gynecologic neoplasms is examined. Approaches to the diagnosis of similar-appearing lesions are presented. PMID- 2184975 TI - Molecular genetic approaches for the diagnosis of clonality in lymphoid neoplasms. AB - Rearrangements of immunoglobulin (Ig) and T cell receptor (TCR) genes provide a highly sensitive molecular marker for the detection of clonality in lymphoid lesions and allow the pathologist to (1) distinguish polyclonal from monoclonal lymphoid proliferations, (2) provide corroborative evidence for lineage when used in conjunction with immunophenotypic techniques, (3) differentiate clonal lymphoid lesions from poorly differentiated nonlymphoid neoplasms, and (4) assess residual disease at the molecular level. The use of these probes in conjunction with morphology and immunohistochemistry or flow cytometry allows the pathologist to assign virtually all lymphoid neoplasms to the B or T cell lineage. The cloning of Ig and TCR genes also has led to the identification of new protooncogenes that reside at the breakpoints of chromosomal translocations frequently observed in lymphoid neoplasms. Molecular probes for these new genes involved in the pathogenesis of lymphoid neoplasms may be used as additional molecular markers for the determination of clonality, lineage, and even histologic subtype of lymphoid neoplasms. Finally, the development of new molecular technologies such as polymerase chain reaction and pulsed-field gel electrophoresis has provided new tools for the highly sensitive detection of genetic rearrangements in human tumors and will greatly enhance the ability of the pathologist to monitor minimal residual disease and detect early relapse. PMID- 2184976 TI - Immunohistochemical diagnosis of nervous system neoplasms. AB - Classic histopathologic study revealed a series of highly treasured criteria for diagnosing central and peripheral nervous system neoplasms. The advent of immunohistochemistry galvanized further improvements in the accuracy of diagnostic neurooncologic pathology, and moreover, enriched our understanding of tumor histogenesis. Now with the tremendous technical advances in immunodetection and the commercial availability of high-quality monoclonal and polyclonal antibodies, the potential for first-rate diagnostic assessment is available to practically every laboratory, regardless of how small or remotely located. Intensive immunohistochemical analysis of nervous system neoplasms has taught us that neuroectodermal cells have a limited repertoire of highly redundant antigenic phenotypes and that neoplastic cells usually mimic their non-neoplastic immature or fully differentiated counterparts. These observations led to the concept that a panel of antibodies ought to be used to identify the "immuno gestalt" of tumors, because it is often difficult if not impossible to subcategorize the tumors on the basis of a single immunohistochemical determination. The ensuing tour through the immunodiagnostic neurooncology summarizes approximately 10 years of original work in this field. I have attempted to provide consensus opinions, and whereever appropriate, highlight dissenting arguments. The salient immunohistochemical features of most nervous system tumors also are summarized in tabular form to facilitate diagnostic considerations at your own institutions. PMID- 2184977 TI - Application of immunohistochemistry in the differential diagnosis of skin tumors. AB - As with neoplasms in any tissue, skin tumors may be categorized as epithelial or mesenchymal, benign or malignant, and primary or metastatic. Immunoperoxidase stains are useful in elucidating the nature of the tumor cells, especially in poorly differentiated tumors. It is important to consider that tumors may exhibit staining patterns different from the typical or reported results. This may be because of intrinsic features of the neoplasm such as the aberrant expression of antigens (markers). Furthermore, the staining of the tumor may be affected by tissue preservation and fixation as well as by the selection of antibodies used for staining. For this reason, the pathologist should be vigilant in comparing the results of unknown tumors with standard controls, with results in the literature, and with his or her own experience. Unusual neoplasms may require additional tissue for analysis, study by other ancillary methods such as electron microscopy, or consultation by more experienced laboratories. These guidelines should be helpful in providing accurate diagnosis of skin tumors. PMID- 2184978 TI - Plastic section immunohistochemistry in the diagnosis of hematopoietic and lymphoid neoplasms. AB - Plastic section immunohistochemistry is an important method in the multiparameter approach to the diagnosis of hematopoietic and lymphoid neoplasms. Morphologic, histochemical, and immunophenotypic data may be correlated even on small fragments of tissue by this technique. A variety of differentiation markers is detectable in plastic sections for the delineation of lymphocytic, histiocytic, and myeloid neoplasms, as well as Hodgkin's disease. Plastic section immunohistochemistry should also be useful in the diagnosis of epithelial and stromal neoplasms caused by enhanced antigen preservation in those neoplasms. For these reasons, we anticipate that the plastic section technique will have a wide variety of research and investigative applications. PMID- 2184979 TI - The potential role of physicians in the management of hospital information systems. AB - The centralized management of manual and automated information systems in hospitals, including the medical record, is usually delegated to administrators rather than to physicians. It is also likely that the importance of automated information systems will increase rapidly as the medical record is electronified. Many significant changes have occurred in recent years relating to the manner in which information systems are managed in hospitals. To address the challenge of this new information environment, hospital Chief Executive Officers (CEOs) have begun to create a new executive hospital position called the Chief Information Officer (CIO). CIOs are included in the hospital executive cabinet and commonly direct all hospital information systems, telecommunications, and management engineering. Although the model of the physician-director of an information system is common at the departmental level with the Laboratory Information System as one example, physicians rarely serve within the central hospital administration as information specialists such as the CIO. Although many physicians would be suitably qualified to serve in this capacity, another option for them would be the position of Chief Medical Information Officer (CMIO) with responsibility for utilization review, medical records, and quality assurance. The CMIO would serve centrally on a part-time basis, continuing to practice simultaneously in a medical specialty. The medical information specialist must not be insulated from the flow of clinical information and discourse with medical colleagues because of the increasing use of information systems for improving work efficiency and the pursuit of quality goals. PMID- 2184980 TI - Immunohistochemistry in surgical pathology. The case of the undifferentiated malignant neoplasm. AB - An ideal immunohistochemical screening panel would be one in which each antibody is 100% sensitive and specific for the target cell type (e.g., markers for epithelial neoplasms, lymphomas, sarcomas, etc.). Anyone who has practiced immunochemistry is well aware that this situation does not exist. High sensitivity is hindered by the loss of key antigens through formalin fixation and routine tissue processing. Although sensitivity can be improved by dealing with fresh-frozen, lyophilized, or plastic-embedded specimens, these procedures are often perceived as inconvenient by pathologists. Specificity is a more insidious problem. With the advent of monoclonal antibody technology, many individuals equated the monospecificity (e.g., marking one antigen a determinant) with tissue specificity. This, of course, is not the case as determinants recognized by one monoclonal antibody may be expressed on cells of different lineage. High sensitivity and high specificity are important for different reasons. By definition, an undifferentiated neoplasm lacks morphologic features to unequivocally substantiate sarcoma, lymphoma, carcinoma, or melanoma. Thus, antibodies with low sensitivity that fail to mark a significant percent of cases will provide inconclusive or erroneous information. The failure of an antibody to stain a particular tissue could be a true-negative (valuable information) or a false-negative (misleading information) result. Obviously, when antibodies have a sufficiently low sensitivity, their use is a liability rather than an advantage. Specificity is obviously important. When an undifferentiated neoplasm is found to be "positive" for a particular marker, there is a tendency to immediately categorize the neoplasm. In this setting, when histologic features of cellular differentiation are totally lacking, an extreme degree of trust is being placed on the immunohistochemical technique. From our earlier discussion it is apparent that perfect sensitivity and specificity do not exist among most immunohistochemical reagents. Accordingly, the safest approach is to use a panel of antibodies that will disclose anomalous immunohistochemical reactions (e.g., a neoplasm positive for both keratin and LCA). Specimens from such cases should be carefully evaluated with additional monoclonal antibodies and scrutinized by light microscopy. Furthermore, while immunohistochemistry provides for rapid and cost-effective diagnosis, electron microscopy may still contribute valuable information. Despite our best intentions and desires, it is also clear that a small percentage of "undifferentiated" neoplasms will remain undifferentiated. Quality control and quality assurance are two final, but important, issues to address. An extraordinary large number of variables in tissue selection, fixation, and processing can skew results.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2184981 TI - The application of monoclonal antibodies in the cytologic evaluation of tumors. AB - The focus of this review has been the application of MAbs as adjuncts in the interpretation of cytology specimens. It is evident that most if not all of the MAbs studied thus far are neither completely tumor-specific nor -sensitive; however, when used to address a directed clinical question, they may be "operationally specific." More important, there continues to be no current substitute for the understanding and practice of sound diagnostic cytopathologic principles. Ultimately, the application of MAbs resides in the importance of tumor-associated antigen expression and phenotyping of tumors with therapeutic and prognostic implications. PMID- 2184982 TI - Evaluation of coagulase-negative staphylococcal isolates from serial nasopharyngeal cultures of premature infants. AB - The present study was undertaken to determine whether very low birth weight infants in a neonatal intensive care unit became colonized with virulent strains of coagulase-negative staphylococci (C-S) over time (i.e., those characterized as Staphylococcus epidermidis, slime positive, and/or multiply antibiotic resistant), and if so, whether the initial colonizing strains developed these characteristics or whether the strains themselves changed. Nasopharyngeal (NP) cultures were obtained weekly on 28 very low birth weight (less than 1750 g) infants hospitalized for a mean of 8 wk (range 4-15 wk). There were 105 isolates of C-S recovered from 96 cultures that were characterized by species, biotype, antibiotic susceptibility pattern, and slime production (screening parameters). Isolates from the same infant with highly similar screening parameters then underwent phage typing and plasmid analysis to increase the likelihood of establishing strain identity. C-S colonization rose from 12% on admission to 75% by wk 2, then gradually declined to 30% by wk 6 and remained stable through wk 10. There were no significant differences among C-S isolates from wk 1 compared with wk 10 of hospital stay with respect to distribution of species, slime positive, or multiply antibiotic resistant strains. One biotype of S. epidermidis was recovered from 46% of study infants, but only one infant was colonized with a predominant biotype of S. epidermidis throughout hospitalization. Thirteen pairs of isolates recovered from 12 of the infants on two or more wk were found to be identical by phage typing and plasmid analysis. Only seven of these 13 pairs of isolates had concordant results for all the screening parameters.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2184983 TI - Frequency of Salmonella typhimurium the year after a massive outbreak. AB - In 1985, Illinois experienced a large milkborne outbreak of Salmonella typhimurium with over 16,000 cases. During this year, 49.4% of United States and 86.4% of Illinois salmonellae were S. typhimurium. In 1986, 1133 microbiologically confirmed and serotyped cases of salmonellosis were reported in the City of Chicago, comprising 37% of the 3034 cases reported for the State of Illinois. The most frequent serotypes were S. typhimurium (21.3%), Salmonella heidelberg (18.2%), Salmonella enteritidis (10.7%), and Salmonella braenderup (7.7%), similar to the state as a whole. Nationally, excluding Illinois, the most frequent serotypes in 1986 were S. typhimurium (26.1%), S. enteritidis (14.7%), and S. heidelberg (13.0%). S. braenderup comprised 0.9% of the non-Illinois total. Regional variations in the epidemiology of salmonellae are probable and may reflect detected or undetected outbreaks. Within a year of the nation's largest Salmonella outbreak, there was no trace of any effect on the frequency of isolation of Salmonella spp. PMID- 2184985 TI - Carotenoids: recent progress, problems and prospects. AB - 1. This is a review of the current state of research on the structure and functions of carotenoids, a common group of natural pigments. 2. Discussed in this paper are recent advances in carotenoid studies and problems that still await elucidation. 3. A new natural nomenclature is proposed to rationalize investigation of biological functions of carotenoids. 4. Data included in the paper are taken from the book, "Biological Functions of Carotenoids" (Karnaukhov, 1988). PMID- 2184984 TI - Effects of terconazole and other azole antifungal agents on the sterol and carbohydrate composition of Candida albicans. AB - The effects of terconazole, a triazole antifungal, on the sterol and carbohydrate composition of Candida albicans was compared with that of three imidazoles: clotrimazole, miconazole, and butoconazole. Exposure of C. albicans to terconazole resulted in a profound depletion of ergosterol with a corresponding increase in lanosterol content versus control cells. Carbohydrate analysis revealed a significant (245%) increase in chitin and a minimal effect on glucan and mannan in terconazole-treated cells. Similar effects on sterol and carbohydrate composition were observed with clotrimazole and miconazole. Butoconazole had a similar effect on sterol composition but had no effect on carbohydrate composition. The decreased ergosterol and increased lanosterol content is consistent with 14 alpha-demethylase inhibition by terconazole and the other azoles. The increase in cell wall chitin is most likely due to deregulation of chitin synthesis secondary to ergosterol depletion in the cell membrane. Because both chitin and ergosterol are critical components of the fungal cell, perturbation of the production and localization of these components by terconazole is likely to contribute to the selective toxicity of this compound for C. albicans and other fungi. PMID- 2184986 TI - Similarities in eukaryotic genomes. AB - 1. The degree of overlap between the human genome and that of other eukaryotes is considered. Biochemical and molecular studies have shown that all eukaryotic organisms evolved from a common progenator that lived several billion years ago. 2. From a geneological point of view, all eukaryotes are related and their genes are all descended from common ancestors. 3. However, most of the DNA in eukaryotic genomes is not transcribed and has been free to drift in nucleotide sequence. Therefore, the question of overlap can only be applied meaningfully to the few per cent of the genome that is expressed. 4. During the last billion years many genes have duplicated and diverged and new genes have been formed by accretion of domains copied from other genes (exon shuffling). 5. The rate of genetic divergence has been such that only a few portions coding for pieces of highly conserved proteins are still shared by all eukaryotes including those that diverged over 600 million years ago. 6. On the other hand, a fairly large number of shared genes can be recognized among species that separated within the last few hundred million years. 7. Human genes have a high degree of identity with homologs in closely related organisms such as other mammals and a decreasing level of identity with their homologs in more distantly related species. PMID- 2184987 TI - Purification and N-terminal characterization of Chinchilla villidera alpha-1 antitrypsin. AB - 1. Chinchilla, Chinchilla villidera, alpha-1-antitrypsin has been purified to homogeneity and partially characterized according to mol. wt, amino acid and carbohydrate composition and N-terminal amino acid sequence (30 residues). 2. The mol. wt is between 52,000 and 55,000 as determined by PAGE or sedimentation equilibrium. 3. The best alignment between chinchilla, human and baboon alpha-1 antitrypsin amino acid sequences offsets the chinchilla sequence 6 positions vs the primate structures. 4. This alignment suggests potential importance of the sequence His-Glu-Gln-Glu-His at positions 11-15. 5. Additionally, the segment Leu Ala-Glu-Phe-Ala, positions 25-29, is strictly conserved. 6. Shorter N-terminal sequences available for rat and rabbit alpha-1-antitrypsin appear to follow the offset alignment vs the primate structures. PMID- 2184988 TI - Comparative structure, function and regulation of isocitrate lyase, an important assimilatory enzyme. PMID- 2184989 TI - Homologies between the amino acid sequences of some vertebrate peptide hormones and peptides isolated from invertebrate sources. AB - 1. The 4K-prothoracicotropic hormone (PTTH) or bombyxin and the melanization reddish coloration hormone of the silkworm Bombyx mori resemble insulin and insulin-like growth factors. 2. The family of adipokinetic/red pigment concentrating hormones has some similarity with glucagon. 3. Members of the FMRFamide family are found in vertebrates as well as in invertebrates. 4. In Locusta, a molecule immunologically and biologically related to amphibian melanophore stimulating hormone has been partially characterized. 5. Enkephalins and enkephalin-related peptides occur in insects and other invertebrates. 6. Peptides belonging to the tachykinin family have been isolated from molluscan (Octopus) salivary glands and from insect nervous tissue (Locusta migratoria). 7. Invertebrate arginine-vasotocin homologs have been isolated from an insect (Locusta migratoria) and from a mollusc (Conus). 8. In Leucophaea, Locusta and Drosophila, peptides resembling those of the vertebrate gastrin/cholecystokinin family have been identified. 9. As the number of different neuro-/gut peptides with possible function(s) as hormone, neurotransmitter or neuromodulator is now estimated to be of the order of a few hundred, more similarities will probably show up in the near future. PMID- 2184990 TI - Isolation, primary structure, and biological and immunological properties of pink and chum salmon insulins. AB - 1. Insulins have been isolated from islet tissue of pink (Oncorhynchus gorbuscha) and chum (Oncorhynchus keta) salmon. The primary structure of chum and pink salmon insulins was found to be identical. Compared to the amino acid sequence of human insulin, the salmon insulins under study differed at 14 positions. 2. Biological activity of pink salmon insulin was 83% of that of standard porcine insulin. 3. The immunological properties of fish insulins were investigated in specific radioimmunoassay (RIA) systems, based on porcine and pink salmon insulins. 4. A significant difference in the antigenic determinants of these fish and mammalian hormones was revealed. PMID- 2184991 TI - Isolation and structure of cecropins, inducible antibacterial peptides, from the silkworm, Bombyx mori. AB - 1. Cecropins, inducible antibacterial peptides, were purified by simple two step chromatography from immunized larval hemolymph of the silkworm, Bombyx mori. 2. The cecropins were further separated into four major and two minor forms by reverse-phase HPLC. 3. The four major cecropins were sequenced and divided into two types, A and B, whose structures were quite similar to cecropins A and B of Hyalophora cecropia. 4. Three of them contained an unusual amino acid, delta hydroxylysine. 5. No remarkable difference in antibacterial activity against E. coli was detected among these cecropins. PMID- 2184992 TI - Extrathoracic staging of bronchogenic carcinoma. AB - In assessing the value of systematic evaluation of extrathoracic extension for potentially resectable, non-small-cell bronchogenic carcinoma, a prospective study was conducted in 146 patients. The study protocol included computed tomographic (CT) scan of the brain and upper abdomen, abdominal ultrasonography, and whole-body bone scanning. The findings were matched with the clinical presentation, histologic features, and TN staging, having found out that non small cell bronchogenic carcinoma does not follow a set pattern to metastasize. The rate of metastasis for adenocarcinoma is not only significantly larger (p less than 0.05) but it does not correlate with the TN staging, in contrast to what happens with the squamous cell carcinoma (p less than 0.01). None of the squamous cell carcinomas in intrathoracic stage I was found to metastasize. Twenty-one percent (4/19) of brain metastases were asymptomatic (three adenocarcinomas and one squamous cell carcinoma with multiorgan metastasis). Bone scanning detected metastasis in 3.4 percent (4/116) of the asymptomatic patients, and three of the four patients with asymptomatic metastasis had nonskeletal foci. In 61 percent (11/18) of patients with hepatic metastasis, we did not find organ specific indicators to suspect it. The series showed a 7.5 percent incidence of adrenal metastasis. Our findings suggest the convenience of performing an upper abdominal CT scan and/or ultrasonography in all patients, except for those with asymptomatic stage I squamous cell carcinoma; we also suggest brain CT scanning for all patients with adenocarcinomas and large-cell carcinomas as well as for those with squamous cell carcinoma with neurologic symptoms, and whole-body bone scanning only in those patients with clinical and laboratory indication of possible bone involvement by metastatic disease. PMID- 2184993 TI - Upper-limb and lower-limb exercise training in patients with chronic airflow obstruction. AB - We designed a randomized controlled study to evaluate the benefit of upper-limb exercise training, alone and in combination with walking training, in patients with severe CAO. In an outpatient department supervised by a physiotherapist, we evaluated 28 patients with severe stable CAO (FEV1, 32 percent of predicted). Patients were randomly allocated to either a control (eight), upper-limb (six), lower-limb (seven), or combined (seven) exercise group. The upper-limb group trained with a circuit of upper-limb exercises, the lower-limb group by walking, and the combined group with both. Exercise was for one hour three times per week for eight weeks. Assessment before and after training included pulmonary function, mouth pressures, respiratory muscle endurance, maximal bicycle exercise test, maximal and submaximal arm ergometer, six-minute walking distance, and a scale of well-being (Bandura scale). Twenty-six patients completed the program. There was a significant improvement (Wilcoxon rank sum test) in the following: six-minute walking distance in the lower-limb (p less than 0.005) and combined (p less than 0.003) groups; arm ergometer in the upper-limb (p less than 0.005) and combined (p less than 0.04) groups; and the scale of well-being in the combined (p less than 0.005) group. There was no significant change in any other parameter measured. We conclude that exercise training improves exercise performance in severe CAO, that the training is specific for the muscle group trained, and that upper-limb exercises should be included in training programs for these patients. PMID- 2184994 TI - The effect of caffeine on exercise-induced bronchoconstriction. AB - The effect of caffeine on exercise-induced bronchoconstriction was examined in ten patients with bronchial asthma. Placebo and caffeine 3.5 mg/kg and 7 mg/kg were given two hours before exercise. Spirometry was taken at one and two hours following caffeine and at 5, 15, and 30 minutes following exercise. Caffeine significantly improved baseline FEV1 and prevented exercise-induced bronchoconstriction only at a dose of 7 mg/kg. Caffeine was well tolerated by the patients. These data suggest that only high doses of caffeine significantly prevent a postexercise drop in FEV1. PMID- 2184995 TI - Hemodynamics during PEEP ventilation in patients with severe left ventricular failure studied by transesophageal echocardiography. AB - The effects of mechanical ventilation with PEEP were investigated in five patients with normal cardiopulmonary function (group A) and in 11 patients with severe left ventricular failure (group B). Cross-sectional area of the right and left atrium (RA/LA), left ventricle (LV), and right ventricle (RV) was determined at EDA/ESA using transesophageal echocardiography. Hemodynamic parameters and transesophageal pressure were measured simultaneously at PEEP levels 0, 4, 8, 12, and 16 cm H2O. End-diastolic area of the right atrium decreased significantly in both groups. The RA pressure increased, while transmural pressure remained unaltered. The CI decreased in both groups. The decrease in cardiac output by PEEP ventilation was related to the decrease in RV filling volume by external compression. In patients with congestive heart failure, PEEP ventilation with 8 to 10 cm H2O did not worsen LV function. PMID- 2184996 TI - Pulmonary edema in severe falciparum malaria. Hemodynamic study and clinicophysiologic correlation. AB - This study was performed to extend the knowledge of the pathogenesis of PE in severe falciparum malaria. Sequential hemodynamic studies were conducted in 13 patients with severe falciparum malaria. Seven patients developed PE, while the other six patients had NPE. Two patients died, one in each group. Hemodynamic changes were found in both groups, including an initial reduction in SVR and PVR, along with an increased CI and variable values (normal and increased) of PCWP. All abnormalities persisted for at least two days; changes in PVR lasted especially longer (throughout five days). The initial hemodynamic changes cannot predict the development of PE; however, heavy parasitemia of more than 60 percent and severe hypoalbuminemia were found to be more common in PE than NPE. Of three patients with PE who had normal PCWP, one died, with postmortem findings of increased pulmonary capillary permeability. The increased PCWP which was found in the other four cases of PE was proven to be volume overload without evidence of CHF. It was concluded that the pathophysiologic changes in severe falciparum malaria were systemic and pulmonary vasodilation. The abnormal pulmonary vascular change was found to be the cause of PE. Volume overload and hypoalbuminemia could aggravate further pulmonary capillary leakage in these cases. PMID- 2184997 TI - Current concepts in prevention of prosthetic valve endocarditis. PMID- 2184998 TI - Ventilator-associated pneumonia in patients with respiratory failure. A diagnostic approach. PMID- 2184999 TI - Cardiovascular effects of sleep disorders. AB - Normal sleep provides a period of physiologically reduced workload for the cardiovascular system for almost one third of the human life span. Snoring, the most common disorder of sleep, heralds the presence of an unstable upper airway and alerts perceptive clinicians to the possibility of OSA. Epidemiologic evidence has implicated snoring as an independent risk factor for the development of hypertension, ischemic heart disease, and cerebral infarction. However, many investigators would attribute these adverse cardiovascular effects to the substantial prevalence of OSA in habitual snorers. The detrimental effects of OSA on hemodynamics and cardiac rhythm have been well documented, and recent data have linked OSA with increased cardiovascular mortality. Worsening hypoxemia during sleep likely contributes to the nocturnal mortality observed in patients with severe COPD. Effective treatment to prevent nocturnal hypoxemia is available for OSA and COPD, with current evidence supporting beneficial effects on survival. PMID- 2185000 TI - Nasal mechanical ventilation (NMV) as an alternative to continuous positive airway pressure (CPAP) in sleep apnea. PMID- 2185001 TI - Utility of CPAP in gastroesophageal reflux. PMID- 2185002 TI - Appendiceal infection by Entamoeba histolytica and Strongyloides stercoralis presenting like acute appendicitis. AB - A 58-year-old male from Puerto Rico who was taking orally administered cortisone analogs for chronic obstructive pulmonary disease presented with fever, absolute eosinophilia, right lower quadrant pain, and rebound tenderness associated with Strongyloides stercoralis infection of the appendix. A 37-year-old alcoholic male developed fever, right lower quadrant abdominal pain, and rebound tenderness because of infection of the appendix with Entamoeba histolytica. These are the seventh reported case of isolated amebic appendicitis and the ninth reported case of appendiceal involvement with Strongyloides. In all these cases the diagnosis was made only after surgery. Patients with unexplained right lower quadrant pain, particularly if immunosuppressed or with an appropriate travel history, should have stool examinations for ova and parasites. Early diagnosis and treatment may prevent life-threatening complications such as perforation and peritonitis. PMID- 2185003 TI - In vitro antibacterial effect of yogurt on Escherichia coli. AB - We investigated the bactericidal and bacteriostatic effects of yogurt on three strains of Escherichia coli: human toxigenic (078:H11), rabbit pathogenic (RDEC 1) and rabbit nonpathogenic [015:K14(L):H4]. Approximately 10(6) organisms were incubated in yogurt, milk, broth, and modifications of these materials. Aliquots were removed at various intervals and plated on MacConkey's agar for enumeration of E. coli. Yogurt was bactericidal (at least 5 log10 reduction in bacterial counts) to all three strains of E. coli with less than 10 CFU/ml remaining by 9 hr. In contrast, all three strains replicated rapidly in milk and broth, reaching maximum concentrations by 9 hr. The E. coli strains survived and multiplied in milk acidified to the same pH as the yogurt. Yogurt (native pH 4.1-4.4) in which the pH was brought up to and maintained at pH 5.5 or pH 7 for 8 hr was not bactericidal to E. coli. Heat-treated yogurt and the filtered supernatant of centrifuged yogurt (both containing no yogurt bacteria) were only bacteriostatic. We conclude that both live yogurt bacteria and a pH near 4.5 are necessary for the bactericidal activity of yogurt. The possibility that yogurt ingestion could protect against infection via other foods contaminated with pathogenic E. coli merits further in vivo investigation. PMID- 2185004 TI - Double cardia. An unusual sequela of reflux esophagitis with ulcer. AB - We report a patient with acquired "double cardia" (esophagogastric fistula). She was a 76-year-old farmer's widow with severe kyphosis. She presented with postprandial heartburn one month after the initiation of nifedipine and isosorbide dinitrate. Radiologic and endoscopic examinations revealed an esophagogastric fistula, short esophagus with hiatal hernia, Barrett's esophagus with reflux esophagitis, and ulcer. This case shows that repeated reflux esophagitis and esophageal ulcer, complicated with short esophagus and hiatal hernia, can predispose to the formation of esophagogastric fistula. PMID- 2185005 TI - Management of a patient with insulin-dependent diabetes mellitus learning biofeedback-assisted relaxation. AB - Psychological stress can have profound disruptive effects upon glycemic control in individuals with diabetes. Presented here is a case study in which biofeedback assisted relaxation techniques were used to help a young woman with a 10-year history of insulin-dependent diabetes mellitus to more effectively manage stress, thereby improving glycemic control. Hypoglycemia is a frequently encountered problem with this technique, so the patient was taught to identify causes of hypoglycemic episodes and to take action to prevent their occurrence. The team approach of a diabetes nurse educator working in conjunction with a biofeedback therapist was vital to the success of this program. PMID- 2185006 TI - Computer-assisted self-control of diabetes by adolescents. AB - This paper reports an experimental investigation of the microcomputer-based system, Diabetes in Self-Control (DISC), used to facilitate adolescents' self management of insulin-dependent diabetes mellitus. Twenty 12- to 19-year-old subjects were matched into 10 pairs and randomly assigned to DISC or conventional education (CE). Following a no-treatment phase, information about diabetes and self-monitoring was presented during 7 weeks of phase 2 by means of computer assisted instruction for the DISC group and printed materials for the CE group. During the 8 weeks of phase 3, DISC subjects received training on monitoring the relationships among variables, diabetes problem solving, and goal setting. Improvement that was both statistically and clinically significant was noted in the DISC group's prelunch and dinner glucose levels. The DISC group showed clinical improvement in frequency of blood glucose testing. Finally, DISC subjects reported more behavioral change as a function of what was learned. PMID- 2185007 TI - Exercise options for persons with diabetic complications. AB - Exercise is a cornerstone in the management of diabetes, yet many persons with diabetes fail to participate in basic physical activity due to secondary diabetic complications. This inactivity can lead to disuse syndrome--a deterioration of functional capacity. Disuse syndrome, coupled with diabetes, can produce significant physiological problems and further disability. This review provides the health educator with information about the pathology and role of exercise for persons with diabetic complications. Examples of exercise to minimize disuse syndrome are given for individuals with peripheral vascular disease, retinopathy, neuropathies, and nephropathy. PMID- 2185008 TI - [Effectiveness and mechanism of action of isoprenaline sulfate and clemastine hydrogen fumarate on histamine wheal-induced pruritus. A placebo-controlled proband study]. AB - In order to investigate the effect of a gel containing isoprenaline and a gel containing clemastine hydrogen fumarate on histamine-induced skin reactions compared with placebo, a histamine solution was injected intradermally in four given fields on the backs of 12 healthy volunteers 15 min and 60 min after application of the gel preparations. The study was controlled by a non-treated field on the volunteers' backs. The main points of interest in this study included the size of the erythema reaction, the capillary blood flow and onset and intensity of itching. With respect to the size of the erythema reaction, both clemastine hydrogen fumarate and isoprenaline proved more effective than placebo in most cases. This superiority was, in some cases, statistically significant. There were no statistically significant differences between the gel preparations for the other parameters investigated. Clemastine hydrogen fumarate is regarded as a classical antihistamine, whereas a possible effect on the superficial circulation of the skin is being discussed for isoprenaline. PMID- 2185009 TI - [Toxicity studies of the incubated chicken egg. With special reference to the extra-embryonal vascular systems]. AB - The use of the incubated chicken egg as a test system to evaluate the effects of hazardous substances is reported. Several different methods to carry out toxicological as well as teratological studies are mentioned. Experimental toxicity testing and basic pathology studies on the extra-embryonal blood vessel systems of the chick embryo (yolk sac system and chorio-allantoic membrane) are described in detail. In this field, the application of the yolk sac system has some advantages compared with the chorio-allantoic membrane. Finally, the use of so-called "alternative methods" and the replacement of the Draize-test and LD50- studies are discussed. PMID- 2185010 TI - Rabbit hemorrhagic disease (RHD)--a new disease and its viral etiology. PMID- 2185011 TI - [Karl Dammann--remembrance of an important veterinarian]. AB - Carl Dammann' 150th anniversary of birth and 75th anniversary of death was in 1989. Therefore Dammann's activities as the last "Direktor" of the School of Veterinary Medicine in Hannover is worth to be documented briefly. Dammann studied Veterinary Medicine and Human Medicine. After that he taught at the School of Agriculture in Proskau and in Eldena (Poland) and later at the School of Veterinary Medicine in Hannover. In the position as the "Direktor" of the School he initiated some important reforms. The present location of the School in Hannover bases on Dammann's activities. In 1899, the Veterinary School of Hannover changed from the "Clever Tor" to the present place at the "Bischofsholer Damm". PMID- 2185012 TI - Antimutagens and anticarcinogens: a survey of putative interceptor molecules. AB - In this review recent publications are cited for a number of antimutagens. The molecules surveyed are potential or proven "desmutagens" or "interceptors." These are biologically prevalent or synthetic molecules that are most often small metabolites proficient in binding to, or reacting with, mutagenic chemicals and free radicals. Many of this class of "blocking agents" are "soft" and "hard" nucleophiles with consequently varying abilities to react with particular classes of electrophiles, the major classes of direct-acting mutagens. Although they serve as a first line of defense against mutagens and carcinogens, many interceptor molecules are under-investigated with regard to their spectra of activity and their possible relevance to prophylaxis or treatment of human disease states. PMID- 2185013 TI - Effects of ageing on transcriptional and post-transcriptional regulation of malic enzyme and glucose-6-phosphate dehydrogenase in rat liver. AB - We previously found an age-dependent impairment of induction of lipogenic enzymes in rat liver [Iritani et al. (1981) Biochim. Biophys. Acta 665, 636-639]. Further, we have found that after refeeding a fat-free diet to fasted rats, increases in transcriptional rate, mRNA concentration and enzyme induction of hepatic malic enzyme and glucose-6-phosphate dehydrogenase were always lower in 18-month-old rats than in 1.5-month-old rats. In the young rats, the transcriptional rates reached the maximum level in 4 h and the mRNA reached maximum levels in 16 h. The peaks tended to delay in the older rats. The half lives of the mRNAs were not significantly longer in the old than in the young animals. The incorporation of [3H]leucine into the enzyme proteins was also decreased roughly in proportion to the enzyme induction. The mRNA concentrations in the liver polysomes were roughly proportional to the total mRNA. Thus, no effects of ageing on mRNA stability or on the translational activity of the enzymes could be found. It is suggested that the age-dependent decreases of malic enzyme and glucose-6-phosphate dehydrogenase induction can be mainly ascribed to the transcriptional steps. Moreover, the transcriptional rate, mRNA concentration and induction of malic enzyme were increased by triiodothyronine treatment at a similar rate in both the young and old rats, but the absolute increments were lower in the old animals. The triiodothyronine response to malic enzyme induction also appeared to be primarily decreased at the transcription level. PMID- 2185014 TI - Cloning and sequencing of mammalian glutathione reductase cDNA. AB - The molecular cloning of a partial cDNA to mouse glutathione reductase mRNA and of a full-length cDNA to the mRNA of the human enzyme is described. An initial cDNA clone designated lambda GRM-B11 was isolated by plaque-screening of an induced mouse cDNA expression library in the lambda gt11 vector with a rabbit antibody probe to human glutathione reductase. 125Iodine-labelled whole anti rabbit immunoglobulin was used as second antibody. EcoRI digestion of the lambda GRM-B11 clone released a 720-bp fragment which was identified as a partial mouse glutathione reductase cDNA by the following techniques. (a) Escherichia coli Y1089 lysogenized with lambda GRM-B11 could be induced to synthesize a recombinant polypeptide whose antigenicity to anti-(glutathione reductase) serum was established by SDS/polyacrylamide gel electrophoresis and subsequent immunoblotting. (b) The GRM-B11 sequence, recloned in the Bluescript vector to give the plasmid pGRM-B11, was found to code for a polypeptide consisting of 242 amino acid residues exhibiting 82% identities with the known amino acid sequence of the human glutathione reductase from position 77 to 318. The insert of the pGRM-B11 plasmid was used as a bona fide nucleic acid probe to screen mouse and human cDNA libraries prepared in the lambda gt11 or in the lambda gt10 vector. The first full-length cDNA clone (lambda GRH-Mev10) was identified in a human cDNA library based on RNA of human placental cells. Its insert was composed of three EcoRI fragments of 720, 613 and 336 bp. The three fragments were recloned in the Bluescript vector and sequenced. The largest fragment (pGRH-B) is colinear with the mouse sequence cloned in the pGRM-B11 plasmid. The fragment of intermediate size (pGRH-CT) comprises the 3' end of the mRNA and the poly(A) tail while the short fragment (pGRH-NT) corresponds to the 5' region of the mRNA. The amino acid sequence deduced from the nucleotide sequences of the three subclones is identical with the known sequence of the mature glutathione reductase from human erythrocytes in all 478 positions. PMID- 2185015 TI - Molecular analysis of the structural gene for yeast transaldolase. AB - We have cloned the structural gene for yeast transaldolase. Transformants carrying the TAL1 gene on a multicopy plasmid over-produced transaldolase. A deletion mutant which was constructed using the cloned gene did not show any detectable transaldolase activity in vitro. Furthermore, both transaldolase isoenzymes which were detected in wild-type crude extracts by immunoblotting were missing in the deletion mutants. Thus, TAL1 is the only transaldolase structural gene in yeast. TAL1 is not an essential gene. Deletion of the transaldolase gene did not affect growth on complete media with different carbon sources or on synthetic media. However, the transaldolase-deficient strains accumulated sedoheptulose 7-phosphate, an intermediate of the pentose-phosphate pathway. Mutants lacking both transaldolase and phosphoglucose isomerase grew more slowly than the single mutants. They accumulated more sedoheptulose 7-phosphate on medium containing fructose than on glucose medium. This shows that fructose 6 phosphate and glyceraldehyde 3-phosphate, metabolites of glycolysis, can enter the nonoxidative part of the pentose-phosphate pathway. PMID- 2185016 TI - Autoregulation may control the expression of yeast pyruvate decarboxylase structural genes PDC1 and PDC5. AB - Recently we deleted the pyruvate decarboxylase structural gene PDC1 from the genome of the yeast Saccharomyces cerevisiae. The pdc1 deletion mutants had pyruvate decarboxylase activity due to the presence of a second structural gene [Schaaff, I., Green, J. B. A., Gozalbo, D. & Hohmann, S. (1989) Curr. Genet. 15, 75-81]. We cloned and sequenced this gene which we call PDC5. The predicted amino acid sequences of PDC1 and PDC5 are 88% identical. Deletion of PDC5 did not cause any decrease in the specific pyruvate decarboxylase activity while pdc1 deletion mutants had 80% of the wild-type activity. Deletion mutants lacking both PDC1 and PDC5 did not show any detectable pyruvate decarboxylase activity in vitro and were unable to ferment glucose. This indicates that PDC1 and PDC5 are the only structural genes for pyruvate decarboxylase in yeast. The PDC5 isoenzyme showed a slightly higher Km value for its substrate pyruvate than the PDC1 product (PDC5: Km = 8 mM; PDC1: Km = 5 mM), as measured in crude extract of pdc1 and pdc5 deletion mutants, respectively. PDC5 is only expressed in pdc1 deletion mutants. No mRNA transcribed from PDC5 could be detected in wild-type cells. Thus, in addition to the control by glucose induction, pyruvate decarboxylase activity seems to be subject to autoregulation. Similar phenomena have been described previously for tubulin, histones and a ribosomal protein but not for metabolic enzymes. PMID- 2185017 TI - The structure of Proteus mirabilis O3 O-specific polysaccharide containing N-(2 hydroxyethyl)-D-alanine. AB - O-Specific polysaccharide was obtained by mild acid degradation of Proteus mirabilis O3 lipopolysaccharide. The polysaccharide was dephosphorylated with 48% HF to give a linear polysaccharide and an amino acid, N-(2-hydroxyethyl)-D alanine. The structure of the polysaccharide was determined by methylation, Smith degradation and computer-assisted analysis of the 13C-NMR spectra of original and dephosphorylated polymers and oligomers. The structure of the amino acid was investigated by using 1H and 13C-NMR spectroscopy and mass spectrometry (applied to the acetylated methyl ester derivative). Its absolute configuration was established by comparison of the optical rotation value and CD spectrum of the natural and synthetic product. On the basis of the data obtained, it was concluded that the repeating unit of P. mirabilis O3 O-specific polysaccharide has the following structure: (formula; see text) Removal of the amino acid phosphate substituent significantly decreased serological activity of the O specific polysaccharide, thus showing the immunodominant role of this group. Serological cross-reactions between P. mirabilis O3 and O27 were demonstrated and tentatively substantiated. PMID- 2185018 TI - Current approaches to macromolecular crystallization. PMID- 2185019 TI - Functional and structural analysis of photosystem II core complexes from spinach with high oxygen evolution capacity. AB - Oxygen-evolving photosystem II core complexes were prepared from spinach by solubilizing photosystem II membrane fragments with dodecyl-beta-D-maltoside. The core complexes consist of the intrinsic 47-kDa, 43-kDa, D1 and D2 polypeptides, the two subunits of cytochrome b559 and the extrinsic 33-kDa protein. In the presence of 50 mM CaCl2 they exhibit a high oxygen evolution rate of 1.3 +/- 0.2 mmol O2.mg chlorophyll-1.h-1 with either 2,6-dichloro-benzoquinone or K3[Fe(CN)6] as acceptor. Electron micrographs of these complexes reveal an obtuse triangular structure in when viewed from the top measuring 15.3 nm on one side and 10.6 nm on the other two sides. An average height of 7.3 nm was determined from the side view position. These data are in good agreement with previously reported dimensions for photosystem II core complexes [Irrgang, K.-D., Boekema, E. J., Vater, J. and Renger, G. (1988) Eur. J. Biochem. 178, 209-217]. In contrast to previous reports the extrinsic 33-kDa subunit could be resolved for the first time. It appears as a small protrusion when the complex is viewed from the side and seems to cover the lumenal side of the core complex appearing as a disk with a thickness of 1.5-3.3 nm. PMID- 2185020 TI - The complete amino acid sequence of the Clostridium botulinum type A neurotoxin, deduced by nucleotide sequence analysis of the encoding gene. AB - A 26-mer oligonucleotide probe was synthesized (based on the determined amino acid sequence of the N-terminus of the Clostridium botulinum type A neurotoxin, BoNT/A) and used in Southern blot analysis to construct a restriction map of the region of the clostridial genome encompassing BoNT/A. The detailed information obtained enabled the cloning of the structural gene as three distinct fragments, none of which were capable of directing the expression of a toxic molecule. The central portion was cloned as a 2-kb PvuII-TaqI fragment and the remaining regions of the light chain and heavy chain as a 2.4-kb ScaI-TaqI fragment and a 3.4-kb HpaI-PvuII fragment, respectively. The nucleotide sequence of all three fragments was determined and an open reading frame identified, composed of 1296 codons corresponding to a polypeptide of 149 502 Da. The deduced amino acid sequence exhibited 33% similarity to tetanus toxin, with the most highly conserved regions occurring between the N-termini of the respective heavy chains. Conservation of Cys residues flanking the position at which the toxins are cleaved to yield the heavy chain and light chain allowed the tentative identification of those residues which probably form the disulphide bridges linking the two toxin subfragments. PMID- 2185021 TI - Different patterns of left ventricular filling in arterial hypertension. AB - To determine whether left ventricular (LV) filling dynamics may be influenced by the type of LV morphological adaptation to arterial hypertension, pulsed Doppler mitral flow velocity recordings were performed in 30 hypertensive patients and in 18 normotensive subjects matched for age, body surface and heart rate. Peak early (E) and late (A) mitral flow velocity, A/E ratio (A/E), time to peak E (TP), acceleration (AHT) and deceleration half-time (DHT) of early mitral flow and isovolumic relaxation time (IRT) were measured. Compared with the control group, hypertensive patients showed prolonged IRT and DHT, increased A and A/E, whereas TP, AHT and E were unchanged. Hypertensive patients were classified into two subgroups on the basis of h/r ratio (h/r). Subgroup 1: 16 patients with normal h/r, less than 0.42, (five patients with increased LV mass index, greater than 129.2 g m-2, and 11 patients with normal LV mass index, less than 129.2 g m-2). Subgroup 2: 14 patients with increased h/r, greater than 0.42, (nine patients with increased LV mass index, greater than 129.2 g m-2 and five patients with normal LV mass index, less than 129.2 g m-2). In Subgroup 1 the cardiac output (CO) was increased and the total peripheral resistance (TPR) was unchanged in comparison with the control group. In Subgroup 2 the opposite haemodynamic profile was detected: normal CO and increased TPR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185022 TI - Outcome of 290 patients with aortic dissection. A 12-year multicentre experience. AB - Retrospective data regarding 290 patients suffering from spontaneous aortic dissection between January 1976 and June 1987 are reported. Dissection was always documented by retrograde aortography and data were collected from 11 catheterization laboratories operating in North-East Italy. The results show that over a 12-year period there was an increase in cases, an increase in the number of operations and a decline in operative mortality. Multivariate discriminant analysis demonstrated that acute myocardial infarction, persistent shock and persistent central neurologic deficit were significant independent predictors of operative mortality in type A patients. Only persistent shock was significantly related to higher operative mortality in type B patients. Late deaths occurred in 14/118 operated patients, and were mostly secondary (directly or indirectly) to aortic dissection. Discharged patients underwent frequent medical checks and chronically received drugs to control hypertension and reduce inotropism. Most of them (73.7%) were asymptomatic: careful post-operative medical assistance is necessary to guarantee the long-term success of surgical treatment. PMID- 2185023 TI - Intravenous carbochromen: a potent and effective drug for estimation of coronary dilatory capacity. AB - Systemic and coronary haemodynamic effects of carbochromen (0.125 mg kg-1 min-1 for 40 min i.v.) and dipyridamole (0.05 mg kg-1 min-1 for 10 min i.v.) were investigated in 18 patients without detectable heart disease. Both drugs induced a comparable increase in coronary blood flow (carbochromen: from 82 +/- 23 to 337 +/- 68 ml.100 g-1.min-1; dipyridamole: from 78 +/- 9 to 301 +/- 61 ml.100 g-1.min 1). This resulted in a minimal coronary resistance of 0.23 +/- 0.04 mmHg.ml-1.100 g.min for dipyridamole and of 0.24 +/- 0.04 mmHg.ml-1.100 g.min for carbochromen. In response to dipyridamole (n = 12) heart rate increased from 73 to 94 beats min 1 (P less than 0.005) and mean aortic pressure fell from 89 to 78 mmHg (P less than 0.001). After administration of carbochromen (n = 6) no significant systemic effects occurred. Dipyridamole induced a significant increase in myocardial oxygen consumption by 46% (P less than 0.001); after application of carbochromen myocardial oxygen consumption remained unchanged. From these data it can be concluded that for the evaluation of coronary dilatory capacity carbochromen may be more suitable than dipyridamole because (1) maximal coronary vasodilation is induced without changes in myocardial oxygen consumption and (2) no systemic effects occur. PMID- 2185024 TI - In vitro analysis of jets by Doppler colour flow imaging: the importance of time to maximum jet area. AB - Regurgitant jets were simulated in vitro and analysed using Doppler colour flow imaging. The regurgitant volumes were estimated using total jet area (JA), variance area (VA), and the maximum area of variance x time to maximum area of variance (MAVT). Both flow rate and injected volume were significantly correlated to area of variance (r = 0.89 and r = 0.98, respectively) for a given orifice size. When MAVT was analysed, it correlated better to injected volume (r = 0.97) at a fixed flow rate, than varying flow rate (r = 0.69) at a fixed injected volume. The relationship between MAVT and injected volume was also examined with varying flow rate. There was a highly significant correlation between MAVT and injected volume under these circumstances (r = 0.99). A similar relationship between MAVT and injected volume was found when the orifice size was altered. Using multivariate regression analysis the injected volume was best defined by MAVT (R2 = 0.88). The addition of orifice size only improved the fit to the model marginally (R2 = 0.90). These data document the importance of analysing the time to maximum area of variance when applying Doppler colour flow imaging to regurgitant jets. MAVT is a better predictor of regurgitant volumes in vitro compared with jet sizes alone and may have potential use in man to quantify the severity of regurgitant valve lesions. PMID- 2185025 TI - Limited joint mobility in insulin dependent childhood diabetes. AB - Limited joint mobility (LJM), beginning typically in the fifth finger and moving radially, affecting interphalangeal, metacarpal-phalangeal, and large joints, is the earliest clinically apparent complication of diabetes in childhood and adolescence. It is painless and not disabling. Approximately 50% of post adolescent patients with more than 5 years duration of diabetes are affected, with age being more important than duration of diabetes, as is the case with other complications. Growth failure is more frequent in the presence of LJM, although correlations with diabetic control have not been found. Variations in frequency in various reports, including high prevalence in controls or relatives, appear to be related to the quality of the examination; simple inspection with hands pressed flat on the table top or together in the prayer position is inadequate; passive extension must be performed. Although differential diagnosis from other conditions causing limitation of the fingers in diabetes would appear simple, LJM has been confused with other conditions which can be distinguished by the presence of pain or paresthesias, neurologic findings, disability, finger locking, swelling, muscle atrophy, palmar skin or fascial thickening, absence of typical distribution, calcification of the vessels and, particularly, the age group affected. That the periarticular thickening found on examination and demonstrated on roentgenograms reflects generalized abnormalities is suggested by association with thick tight waxy skin, decreased pulmonary function, and association with retinopathy, nephropathy, and neuropathy, independently of duration of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185027 TI - Special education and the regular education initiative: basic assumptions. AB - The regular education initiative (REI) is a thoughtful response to identified problems in our system for educating low-performing children, but it is a not a detailed blueprint for changing the system. Educators must achieve consensus on what the REI actually proposes. The authors infer from the REI literature five assumptions regarding the roles and responsibilities of elementary regular classroom teachers, concluding that these teachers and specialists form a partnership, but the classroom teachers are ultimately in charge of the instruction of all children in their classrooms, including those who are not succeeding in the mainstream. A discussion of the target population and of several partnership models further delineates REI issues and concerns. PMID- 2185026 TI - A European multicenter randomized controlled trial of single dose surfactant therapy for idiopathic respiratory distress syndrome. AB - We performed a multicenter prospective randomized controlled trial to determine the efficacy and safety of the surfactant preparation, Survanta (Abbott Laboratories, Chicago, USA), for 750-1750 g infants with idiopathic respiratory distress syndrome, (IRDS) receiving assisted ventilation with 40% or more oxygen. One hundred and six eligible infants from the eight participating centers were randomly assigned between March 1986 and June 1987 to receive either surfactant (100 mg phospholipid/kg, 4 ml/kg) or air (4 ml/kg) administered into the trachea within 8 h of birth (median time of treatment 6.2 h, range 3.2-9.1 h). The study was stopped before enrollment was completed at the request of the United States Food and Drug Administration when significant differences were observed in incidence of periventricular-intraventricular hemorrhage (PIH), between the surfactant treated and control infants. Surfactant treated infants had larger average increases in the arterial-alveolar oxygen ratio, (a/A ratio) (P less than 0.0001), and larger average decreases in FiO2 (P less than 0.0001) and mean airway pressure, (MAP) (P less than 0.017) than controls over the 48 h following treatment. The magnitude of the differences between the surfactant and control groups were 0.19 (SE = 0.03) for a/A ratio, -0.28 (SE = 0.04) for FiO2 and -1.7 cm H2O (SE = 0.70) for MAP. The clinical status on days 7 and 28 after treatment was classified using four predefined ordered categories: (1) no respiratory support; (2) supplemental O2 with or without continuous positive airway pressure (CPAP); (3) intermittent mandatory ventilation; and (4) death. There were no statistically significant differences in the status categories on days 7 or 28 between surfactant and control infants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185028 TI - Potent thromboxane-mediated in vitro bronchoconstrictor effect of endothelin in the guinea-pig. PMID- 2185029 TI - Instability of the myofibroblast phenotype in culture. AB - Myofibroblasts are cells that have features of both smooth muscle cells and fibroblasts. Myofibroblasts from rat granulation tissue were studied using a coordinated biochemical and morphological approach. These myofibroblasts were maintained in culture for more than 17 passages. After establishing that these cells were indeed myofibroblasts by immunohistochemical and ultrastructural criteria, their biochemical parameters and phenotypic stability were studied. Rat dermal fibroblasts grown under similar conditions served as controls. Biochemically, it was found that both cells produced similar types of procollagens, namely collagens I and III, in similar proportions at or near a 1:1 ratio. However, myofibroblasts at early passage produced threefold more procollagens than did fibroblasts at the same stage of passage, while similar quantities were produced in each at late passage. These observations for procollagens were confirmed by separate studies for collagens, as measured by hydroxyproline determinations. Such differences were also reflected ultrastructurally. Secretory vesicles were identified in myofibroblasts at early stage, but not at late stage of passaging. No such vesicles were seen in fibroblasts at any stage of passage. In conclusion, myofibroblasts are active secretory variants of fibroblasts which have an unstable phenotype in culture and become indistinguishable from fibroblasts at late passage. PMID- 2185030 TI - A common mechanism of transcriptional activation by the three positive regulators, VirG, PhoB, and OmpR. AB - VirG, PhoB, and OmpR are positive regulators of the virulence, phosphate, and osmolarity regulons, respectively. Their target genes are attended with one or more significant blocks of similar 6-bp sequences in their regulatory regions. The distance between the block(s) and transcriptional start site varies with the target genes, but the blocks are located in a similar manner phase-specific to the promoter sequences. On the basis of these facts, we offer a novel model of transcriptional activation common to these regulators. PMID- 2185031 TI - Receptor-active glycolipids of epithelial cells of the small intestine of young and adult pigs in relation to susceptibility to infection with Escherichia coli K99. AB - Glycolipids from mucosa scrapings of small intestine of neonatal and adult pigs were tested by the thin-layer chromatogram overlay assay for the binding of Escherichia coli K99. There was practically no binding to acid or non-acid glycolipids of adult pig, known to be resistant to infection with this bacterium. However, piglets, which are susceptible to infection, showed a clear binding to a doublet band in the acid glycolipid fraction. The receptor-active glycolipid was isolated and shown by mass spectrometry, NMR spectroscopy and degradation methods to be NeuGc alpha-3Gal beta 4Glc beta Cer (NeuGc-GM3), the two bands being due to heterogeneity of the ceramide. When tested against various reference glycolipids, NeuAc-GM3 was shown to be inactive. This ganglioside was dominating in adult pig. The apparent developmental disappearance of N-glycolyl groups in glycolipids of intestinal mucosa may have a correspondence in protein-linked sequences as well as thus explain the resistance of adult pigs to infection with E. coli K99. PMID- 2185032 TI - DNA methylation in Trypanosoma cruzi. AB - DNA isolated from the protozoan Trypanosoma cruzi has been found to contain 5 methylcytosine. Analysis of T. cruzi DNA by both HpaII and MspI restriction endonucleases suggests that the sequence -CCGG- is not methylated. Probably T. cruzi DNA also contains N6-methyladenine. This report constitutes the first clear demonstration of the presence of methylated bases in the nuclear DNA from trypanosomes. PMID- 2185034 TI - Factor Xa cleavage of fusion proteins. Elimination of non-specific cleavage by reversible acylation. AB - A method is described for the elimination of non-specific cleavage of fusion proteins by factor Xa. Putative non-specific cleavage sites C-terminal to lysyl residues are blocked by reversible acylation by 3,4,5,6-tetrahydrophthalic anhydride prior to cleavage. After cleavage, the acyl groups are removed quantitatively by exposure to slightly acidic conditions. This method employs no harsh reagents or conditions, and may be generally applicable to factor Xa cleavage of fusion proteins. PMID- 2185033 TI - The interaction of actin with dystrophin. AB - Proton NMR spectroscopy of synthetic peptides corresponding to defined regions of human dystrophin has been employed to study the interaction with F-actin. No evidence of interaction with a C-terminal region corresponding to amino acid residues 3429-3440 was obtained. F-actin restricted the mobility of residues 19 27 in a synthetic peptide corresponding to residues 10-32. This suggests that this is a site of F-actin interaction in the intact dystrophin molecule. Identical sequences to that of residues 19-22 in dystrophin, namely Lys-Thr-Phe Thr are also present in the N-terminal regions of the alpha-actinins implying this is also a site of F-actin interaction with alpha-actinin. PMID- 2185035 TI - Peptidyl-prolyl cis-trans isomerase does not affect the Pro-43 cis-trans isomerization rate in folded calbindin D9k. AB - The calcium-binding protein calbindin D9k has previously been shown to exist in two folded forms only differing in the proline cis-trans isomerism of the Gly-42 Pro-43 amide bond. This bond is located in a flexible loop connecting the two EF hand Ca2+ sites. Calbindin D9k therefore constitutes a unique test case for investigating if the recently discovered enzyme peptidyl-prolyl cis-trans isomerase (PPIase) can affect the cis-trans exchange rate in a folded protein. The 1H NMR saturation transfer technique has been used to measure the rate of interconversion between the cis and trans forms of calbindin in the presence of PPIase (PPIase:calbindin concentration ratio 1:10) at 35 degrees C. No rate enhancement could be detected. PMID- 2185036 TI - 'Quantal' Ca2+ release and the control of Ca2+ entry by inositol phosphates--a possible mechanism. AB - The release of Ca2+ from intracellular stores by sub-optimal doses of inositol trisphosphate has been shown to be dose-related ('quantal'), and a simple model is proposed here to account for this phenomenon. It is suggested that there is a regulatory Ca2(+)-binding site on, or associated with, the luminal domain of the InsP3 receptor, which allosterically controls Ca2+ efflux, and the affinity for Ca2+ of that site is modulated by InsP3 binding to the cytoplasmic domain of the receptor; a similar mechanism applied to the ryanodine receptor might also explain some aspects of Ca2(+)-induced Ca2+ release. The stimulated entry of Ca2+ into a cell which occurs upon activation of inositide-linked receptors has been variously and confusingly proposed to be regulated by InsP3, InsP4, and/or a 'capacitative' Ca2+ pool; the mechanism of InsP3 receptor action suggested here is shown to lead to a potential reconciliation of all these conflicting proposals. PMID- 2185037 TI - Structural kinetics of the allosteric transition of aspartate transcarbamylase produced by physiological substrates. AB - We have studied the kinetics of the quaternary structure change associated with the allosteric transition of aspartate transcarbamylase (ATCase) (E. coli), inducing this change by exposure to the natural substrates (carbamyl phosphate and L-aspartate). The presence of 30% ethylene glycol slowed the quaternary structure change sufficiently for it to be followed by stopped-flow X-ray scattering at -5 degrees C. After adding substrates to the enzyme, the change occurred, with a half-life of a few seconds, yielding a mixture of the two standard quaternary structures (or, conceivably, a state intermediate between them). This mixture persisted until the enzyme reduced the substrate concentration below a threshold value. PMID- 2185038 TI - Purification and study of a bacterial glutathione S-transferase. AB - A glutathione S-transferase from Escherichia coli has been purified approximately 800-fold with an 11% activity yield by passage through DEAE Sephacel and glutathione-agarose affinity columns. Its functional form is a homodimer of two 24,000 Da polypeptides that catalyzes the binding of glutathione and 1-chloro-2,4 dinitrobenzene with Km values of 0.25 and 1.5 mM, respectively. Optima of pH and temperature were 7.5 and 35 degrees C. The activity was stimulated (30%) by ethylenediaminetetraacetic acid. The N-terminal amino acid sequence was: Met-Leu Leu-Phe-Ile-Leu-Pro-Gly-Ala. PMID- 2185039 TI - Potential utility of gonadotropin-releasing hormone agonists in the management of ovarian hyperandrogenism. AB - Gonadotropin-releasing hormone agonists are potent suppressors of ovarian androgen biosynthesis even in the face of severe hyperandrogenism (e.g., hyperinsulinemia, hyperthecosis). Gonadotropin-releasing hormone agonists are clinically useful in the context of hirsutism. The use of Gn-RH-a in the context of hirsutism is not duration-limited in that the induced hypoestrogenism and its consequent complications are likely to be effectively managed by the concurrent provision of estrogen replacement therapy. PMID- 2185040 TI - Dysregulation of cytochrome P450c 17 alpha as the cause of polycystic ovarian syndrome. AB - Polycystic ovarian syndrome (PCOS) appears to be due to a previously unrecognized type of steroidogenic abnormality, one in which hyperandrogenism arises from a regulatory abnormality (dysregulation) rather than from enzyme deficiency. It appears that PCOS typically arises from masculinized regulation of the androgen forming enzyme (cytochrome P450c17 alpha) within ovarian thecal cells. This may arise by either excessive stimulation by luteinizing hormone (LH) or by escape from desensitization to LH. We review evidence which is compatible with the concept that the latter situation may result from an intrinsic intraovarian flaw in the paracrine feedback mechanism by which thecal androgen biosynthesis is inhibited and that coexistent adrenal 17-ketosteroid hyper-responsiveness to corticotropin (ACTH) may be due to a similar type of dysregulation of adrenocortical P450c17 alpha. PMID- 2185041 TI - Evaluation of a simple and fast self-test for urine luteinizing hormone. AB - Ovulation can be predicted by measuring the midcycle urine luteinizing hormone surge with a simple 5-minute enzyme-immunoassay. This assay has proved to be suitable for self-tests with a sensitivity of about 90% and a specificity of 100% in unstimulated and clomiphene citrate stimulated cycles. Whereas a reference method (hemagglutination test) yielded better sensitivity, its specificity was markedly worse. Self-tests carried out by patients and control laboratory tests showed an excellent correlation. Patient compliance with self-tests should not be taken for granted. PMID- 2185042 TI - Intrauterine insemination does and clomiphene citrate does not improve fecundity in couples with infertility due to male or idiopathic factors: a prospective, randomized, controlled study. AB - In the present prospective study we compared, in terms of pregnancy rates, the differences between intrauterine insemination (IUI) of in vitro capacitated husband's semen and timed natural intercourse in spontaneous or clomiphene citrate (CC) stimulated cycles. A rapid urinary luteinizing hormone peak detection test was used for timing of ovulation. Forty patients suffering from longstanding infertility of male (n = 17), cervical (n = 2), and idiopathic (n = 21) origin were randomly assigned into four distinct treatment modalities during 4 consecutive cycles. A total of 132 cycles were analyzed. In 35 cycles treated with CC plus IUI, five conceptions were achieved, whereas three pregnancies occurred in 32 inseminated spontaneous cycles. Only 1 patient conceived after timed intercourse in 31 CC stimulated cycles, and no pregnancy resulted from 34 spontaneous cycles combined with timed intercourse. There was a statistically significant higher conception rate in cycles in which IUI was performed, whereas the use of CC does not seem to improve the pregnancy rate. Analysis of results for other modifying factors did not substantially affect the relative risk (odds ratio) of pregnancy. PMID- 2185043 TI - Follicle cysts after menstrual versus midluteal administration of gonadotropin releasing hormone analog in in vitro fertilization. AB - The incidence and behavior of follicle cysts after different timing of gonadotropin-releasing hormone analog (GnRH-a) administration was studied in 321 in vitro fertilization (IVF) cycles. Group M included 198 cycles in which GnRH-a was injected at menstruation. Of these, 171 (88.6%) were without cysts (group M1) and 27 (13.6%) with cysts (group M2). Group L comprised of 123 cycles in which GnRH-a was administered in the midluteal phase. Of them, 70 (56.9%) were without cystic finding (group L1), 19 (15.4%) with follicle cysts (group L2), and 34 cases (27.6%) with visible corpus luteum at the time of GnRH-a initiation (group L3). Both groups with follicle cysts demonstrated a higher luteinizing hormone peak and continuous elevated estradiol (E2) levels. In group M2, the E2 rise and the cysts persisted longer compared with group L2. Gonadotropin treatment was accordingly postponed until the cysts regressed spontaneously. Only two cases of group M2 required aspiration of the cysts. Follicle cyst formation is not related to the timing of GnRH-a administration and their occurrence did not have adverse effects on IVF outcome. PMID- 2185044 TI - Effect of sperm morphology and motile sperm count on outcome of intrauterine insemination in oligozoospermia and/or asthenozoospermia. AB - Eighty-six couples with long-standing infertility and poor postcoital test, due to oligozoospermia and/or asthenozoospermia (68 cases) or mucus hostility (18 cases), were treated by 411 intrauterine inseminations (IUI) with motile sperm suspensions from the husband's semen. The pregnancy rate per couple in the group with abnormal semen was lower than in the group with mucus hostility (22% versus 38.9%). Influence of seminal and other parameters on outcome of IUI was assessed by discriminant analysis, and a significant correlation with pregnancy rate was found for motile sperm count and sperm morphology. Teratozoospermia (normal morphology less than 50%) affected the outcome of IUI both when associated with moderate oligozoospermia and/or asthenozoospermia (motile sperm count greater than or equal to 5 X 10(6)/mL) (success rate per couple: 11.1%), and, even more, when associated with severe oligozoospermia and/or asthenozoospermia (motile sperm count less than 5 X 10(6)/mL), where no pregnancy was achieved. In the absence of teratozoospermia, the success rate per couple both in severe and in moderate oligozoospermia and/or asthenozoospermia had similar results (33.3% versus 35.7%). In conclusion, the absence of teratozoospermia appears to be an effective criterion for selecting couples with infertility due to oligozoospermia and/or asthenozoospermia who may benefit from IUI. PMID- 2185045 TI - Ultrasonically guided vaginal aspiration of ascites in the treatment of severe ovarian hyperstimulation syndrome. AB - This study included 11 cases of severe OHSS that were treated by transvaginal aspiration of the ascitic fluid guided by ultrasound. Immediate improvement of the symptoms and general condition as well as a significantly shorter hospital stay was noticed when compared with the control group. It is a safe and simple procedure that does not require anesthesia. PMID- 2185047 TI - 3 ways to manage stress. PMID- 2185048 TI - Waxman introduces Medicaid AIDS bill. PMID- 2185046 TI - Nonsurgical treatment of a viable cervical pregnancy with intra-amniotic methotrexate. AB - Although a rare complication of gestation, the possibility of fertility loss is no more serious than with a cervical pregnancy. A case of a viable cervical pregnancy treated with ultrasound guided transabdominal aspiration and intra amniotic methotrexate administration is presented. When the diagnosis is made early in gestation this method should be considered for the treatment of a cervical pregnancy when future fertility potential is desirable. PMID- 2185049 TI - [In vivo insulin sensitivity in adrenodemedullated rats]. AB - Insulin sensitivity and responsiveness were determined in adrenal demedullated rats (ADMX) with euglycemic insulin clamp technique. Adrenal medulla was extirpated bilaterally a week before the study. Catheters were placed at right atrium via right jugular vein for sampling blood and at inferior vena cava via femoral vein for the infusion of insulin and glucose solution. Insulin was infused at rates of 4.4, 8.8, 14.7, 29.3, 88.0, 293.0 mU/kg/min. Blood was collected every five min. during the clamp and glucose infusion rate was modulated to control the blood glucose concentrations at fasting levels. Glucose metabolism was calculated from the amount of glucose infused from 60th to 120th min. during the euglycemic clamp. The results obtained were as follows: 1. Glucose metabolisms of ADMX in each infusion rate of insulin, 4.4, 8.8, 14.7, 29.3, 88.0, 293.0 mU/kg/min were 5.2 +/- 0.5, 12.5 +/- 0.5, 17.6 +/- 1.2, 19.8 +/ 2.3, 29.0 +/- 1.5, and 25.2 +/- 1.9 mg/kg/min, respectively. 2. Glucose metabolisms of control group in each dose were 6.6 +/- 0.4, 9.0 +/- 0.9, 18.5 +/- 1.2, 23.4 +/- 2.4, 24.6 +/- 1.1, and 27.0 +/- 1.3 mg/kg/min, respectively. 3. Significant difference (p less than 0.01) in glucose metabolism between ADMX and control was observed at the insulin infusion rate of 8.8 mU/kg/min which might be equivalent to physiological hyperinsulinemia. 4. There were not any differences in insulin responsiveness between both groups. These results suggest that epinephrine regulates insulin sensitivity under physiological hyperinsulinemic condition via defects of insulin receptors. PMID- 2185050 TI - SPECT. An update and review of clinical indications. PMID- 2185051 TI - Age-specific death rates with tobacco smoking and occupational activity: sensitivity to sample length, functional form, and unobserved frailty. AB - In this article, we estimate accelerated time-to-failure and proportional-hazard functions with about 100,000 members of the Dorn sample, finding greater hazards associated with smoking and some dependence on occupational variables that measure risk and physical activity. We answer three questions: (1) How sensitive are the estimates to sample length, using monthly data for the periods 1954-1969 and 1954-1980? The results differ somewhat between these sample periods. (2) How sensitive are the estimates to alternative functions for the hazard? Within a given time period, the estimates are fairly robust to specification changes in the distribution of the hazard in the accelerated time-to-failure models. (3) How sensitive are the estimates to alternative controls for unobserved frailty? Within a given sample period, the estimates are fairly robust to the allowance for parametric or nonparametric heterogeneity in the proportional-hazard models. PMID- 2185052 TI - [Diabetes and hemorheology]. AB - Diabetes is associated with several types of rheological abnormalities: 1. macrorheological ones, consisting of increased whole blood viscosity and plasma viscosity; 2. microrheological ones, consisting of a change in erythrocyte deformability, an increase in erythrocyte aggregation and in their adhesiveness to endothelial cells. Microrheological abnormalities in the leukocytes and platelets are associated with these changes and may precede them. Certain of these abnormalities are particularly observed in diabetics with macro and/or microangiopathy and may contribute to a reduction in tissular oxygenation and to the vascular complications of diabetes. The precise mechanisms remain to be clarified as well as the part played by the hypertension often found in diabetes. PMID- 2185053 TI - Salivary immunoreactive insulin concentrations are related to plasma free-insulin levels in insulin-treated diabetic patients. AB - Salivary immunoreactive insulin was measured in 45 insulin-treated diabetic patients directly from saliva samples by a radioimmunoassay procedure. Mean and median fasting salivary immunoreactive insulin was respectively 88.5 and 54.0 pmol/L (range 12.2-633.6 pmol/L); fasting salivary insulin values were positively correlated with steady-state plasma free-insulin levels measured in immediately extracted plasma samples (r = 0.62, p less than 0.001) and with daily insulin dose (r = 0.32, p less than 0.05). After subcutaneous injection of 15 U regular insulin in 6 type 1 diabetic patients, salivary insulin concentrations increase reflected that of plasma free-insulin during a 6 h period although with a 60 min time lag. Mean salivary insulin values and plasma free-insulin concentrations were significantly correlated to each other both at each time point (p less than 0.001) and when the mean salivary insulin levels were plotted against the mean plasma free-insulin values 60 min earlier (p less than 0.001). These results suggest that the measurement of salivary immunoreactive insulin (that is easier, faster and cheaper than plasma free-insulin assay) may be usefully employed as an approximation of plasma free-insulin concentrations for clinical and research purposes in patients with circulating anti-insulin antibodies. PMID- 2185054 TI - Interactions between endogenous and exogenous insulin and human pancreatic polypeptide secretion. AB - The relationships between exogenous and endogenous insulin and plasma human pancreatic polypeptide (hPP) were investigated. Three tests were performed in 8 healthy subjects: 1 degree--1 g tolbutamide was injected i.v. in 1 min., 2 degrees--50 ml 50% glucose solution and 7 U of Insulin were contemporaneously infused at constant rate for 60 min., 3 degrees--50 ml saline solution were infused as control. After the tolbutamide injection plasma glucose levels were unchanged between 0-10 min. At 5, 10, 15 min. an increase in C-Peptide (CPR) value and a significant decrease of hPP were observed. At 15, 30 and 45 min. plasma glucose was significantly lower than baseline and hPP levels strongly rose until the end of the test. The glucose-insulin infusion testing resulted in a rise in plasma glucose and CPR levels at 15 min. and a fall in plasma hPP at 30 min. The present findings suggest that in the first part of tolbutamide test, the endogenous insulin secretion, valued as CPR, seems to inhibit hPP release probably through a paracrine pathway. PMID- 2185055 TI - Long term reduction of microalbuminuria after 1 year of angiotensin converting enzyme inhibition by perindopril in hypertensive insulin-treated diabetic patients. AB - We studied the effects of perindopril, an angiotensin converting enzyme (ACE) inhibitor administered during 12 months, on creatinine clearance, albuminuria and glycaemic control in diabetic subjects with mild to moderate hypertension. After 1 month placebo, 40 insulin-treated patients were divided into 3 groups based upon their urinary albumin excretion rate (AER). Group I had a normoalbuminuria (AER less than 15 mg/24 h), group II had a microalbuminuria (AER : 15-150 mg/24 h) and group III had a macroproteinuria (AER greater than 150 mg/24 h and Albustix (+)). They were given perindopril, 4 to 8 mg orally once daily, and received a stable diet. Diastolic blood pressure was normalized within the first 3 months in 80% of the patients. From these, 28 (14.7 and 7 from groups I, II and III respectively) were followed during a total active treatment period of 12 months. They were matched for age, duration of diabetes and hypertension, systolic and diastolic blood pressures, daily insulin dose, postprandial plasma C peptide and quality of glycaemic control. Mean supine diastolic blood pressure was decreased by 15 and 18% at 1 and 12 months respectively. Heart rate was not significantly modified. At 3 months, plasma ACE activity was nearly totally inhibited while plasma renin activity was markedly increased. In patients of group II, microalbuminuria was reduced from 66 +/- 13 (mean +/- SEM after placebo) to 39 +/- 6 mg/24 h after 1 month perindopril and this effect was maintained at 12 months. In group I, albuminuria remained within the normal range. In group III, macroproteinuria was not consistently modified by perindopril.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185056 TI - Nonspecific delivery of substances into pancreatic islet cells by pH-sensitive liposomes in vitro. AB - The aim of this study was to evaluate the suitability of different liposome preparations for translocation of substances into the pancreatic islet cell in vitro. For this purpose, isolated islets, either fresh or cultured or dispersed islet cells from the rat were incubated with different liposome preparations containing 6-carboxyfluorescein. The composition of the liposomes was either phosphatidylcholine/ganglioside (pH-insensitive) or phosphatidylethanolamine/oleic acid (pH-sensitive). Non-specific immunoglobulin was attached to the liposome membrane by means of covalent conjugation or by dialysis. Following incubation with the different liposomes, the islets were dispersed and examined in a fluorescence microscope for assessment of intracellular fluorescence emitted by the liposome-delivered fluorescein. It was found that the delivery of liposomal contents into islet cells was the least when using the pH-insensitive liposomes. The delivery could be slightly increased if immunoglobulin was conjugated to these liposomes. Intracellular fluorescence arising from pH-sensitive liposomes was clearly stronger than that from pH insensitive liposomes. The use of pH-sensitive liposomes with conjugated IgG, however, failed to improve the delivery. When the proportions of fluorescent cells in the different islet preparations were compared, there was a higher percentage of such cells in the freshly isolated islets and in the dispersed islet cells than in the cultured islet cells. To quantitate the liposome mediated delivery of substances, cells in suspension, from a insulin producing tumor cell line (RINm5F) of from dispersed rat islets, were incubated with carboxyfluorescein containing liposomes and the intracellular release of the fluorescein was followed spectrofluorometrically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185057 TI - [Should the assay of fructosamine be part of the elements of diabetic monitoring?]. PMID- 2185058 TI - Vascular and insulinotropic effects of YC 170, a calcium agonist, on isolated perfused rat pancreas. AB - To explore simultaneously the effects on insulin secretion and on vascular tone of YC 170, a new dihydropyridine derivative calcium agonist, isolated perfused rat pancreases were studied for insulin output and for duodenopancreatic resistances before, during and after exposure to YC 170 10(-4) M (n = 15) or its solvent (n = 10). Although insulin was stimulated transiently during the five first minutes following addition of YC 170 (p less than 0.01) the integrated insulin output measured during the whole experiments was not different with YC 170 from that observed with solvent. Conversely, the initial duodenopancreatic resistances (22 +/- 4 mmHg.ml-1.min-1) rose progressively with YC 170 up to maximal values at the end of experiments (104 +/- 28 mmHg.ml-1.min-1; p less than 0.01); no significant variation occurred with solvent. Vascular and insulinotropic effects of YC 170 can be dissociated, suggesting variable abilities to promote calcium transport across membranes of smooth muscle cells and of pancreatic B-cells. PMID- 2185060 TI - Antithrombin III. PMID- 2185059 TI - Biochemical consequences of phosphorylcholines low pK with special relevance to human semen: passive pH regulation. AB - 1. The significant difference in pK between phosphorylcholine (PCh) and inorganic phosphate (Pi) of over 1 pH unit results in PCh being a source of acid buffering potential and an actual sink for protons when it is hydrolyzed. Phosphorylethanolamine (PEth) can fill the same role. 2. Both semen and tissues having substantial anaerobic metabolism among which are those of fetal origin can face circumstances of non-pathological acidosis. 3. We demonstrate from the literature that all of those tissues with the two understandable exceptions of erythrocytes and striated muscle, have high levels of PEth and/or PCh. 4. Since these phosphomonoesters can serve as lipid metabolites as well as low-pK fixed phosphate buffer it appears they can serve a dual function in these tissues. 5. Their concentration would vary depending on the physiological and biochemical conditions present and we would call this a "Swiss army knife" theory of metabolic function. PMID- 2185061 TI - Retrospectives and perspectives on the biological activity of histidine containing dipeptides. AB - 1. An evaluation of the biological function of histidine-containing dipeptides, is presented. 2. These have been found to be potent pH-buffering compounds, strong antioxidants and membrane stabilizers. 3. Analysis of the biological and biomedical properties of carnosine and other related dipeptides suggests their use as universal membrane repairing compounds. PMID- 2185062 TI - Effect of diabetes and time after in vivo insulin administration on ketogenesis and gluconeogenesis in isolated rat hepatocytes. AB - 1. Diabetic rats had elevated rates of gluconeogenesis and ketone body production. 2. Four hours after insulin administration the rate of gluconeogenesis returned to normal and the rate of ketogenesis decreased with certain substrates, but did not return to normal. 3. Eight hours after insulin treatment ketogenesis from all substrates was significantly reduced, but still significantly higher than normal. PMID- 2185064 TI - Kinetics of ligand binding to haemoproteins. AB - A mass of experimental data has been accumulated in the 65 years since Hartridge and Roughton made the first measurement of the rapid reaction of haemoglobin with O2 in solution on a millisecond time scale, at first by flow-mixing methods, and, for 30 years or so, by flash photolysis. Technical advances, particularly in lasers, have allowed increasingly rapid reactions to be followed and the fastest reactions now observed have half-times conveniently measured in pico-seconds. The measurements were used at first to discuss the physiology of gas transport and to describe co-operativity in haemoglobin. More recently, the process of ligand binding has been dissected into intramolecular and intermolecular components. Relating the various rates to the abundance of structural information on crystals is so difficult that the work has barely begun, but the combination of kinetic measurements with genetic engineering and crystallography has promise, as well as problems, for the future. PMID- 2185063 TI - Regulation of mitochondrial ATP synthesis in mammalian cells by transcriptional control. AB - 1. Mitochondrial ATP synthesis (oxidative phosphorylation) is mainly regulated by the membrane potential (respiratory control) and protein synthesis (transcriptional control). 2. According to the current view, genes for enzymes of oxidative phosphorylation are classified as housekeeping genes that are transcribed constitutively. These genes have been sequenced. 3. Four complexes of oxidative phosphorylation (complexes I, III and IV, and ATP synthase) are exceptional oligomers that contain subunits encoded by mitochondrial DNA. The remaining subunits of these complexes, as well as thousands of other mammalian enzymes are encoded by nuclear DNA. 4. It is proposed that ATP synthase (F0F1) and these oligomers supplying energy to F0F1, though they are housekeeping, are under some coordinated transcriptional control. Not transcription, but translation of mitochondrial DNA is mainly regulated. 5. Recently, studies on cloned human genes for the FoF1 beta subunit and 7 enzymes related to ATP synthesis revealed coordinated transcription. Moreover, a novel common cis element (enhancer) was discovered in the 5'-upstream region of genes for the F1 beta subunit, cytochrome c1 and pyruvate dehydrogenase E1 alpha subunit. 6. In contrast to heme control and catabolite repression of yeast via trans-acting elements such as HAP and GP, signal transduction and coordinated transcription of human oxidative phosphorylation is not directed by CP1 (a HAP homolog), but may be closely related to cell differentiation. PMID- 2185065 TI - From 14 alpha-demethylase inhibitors in fungal cells to androgen and oestrogen biosynthesis inhibitors in mammalian cells. PMID- 2185066 TI - The role of the entero-insular axis in insulin secretion. PMID- 2185067 TI - Intra-islet cellular interrelationships. PMID- 2185068 TI - Hexose recognition mechanisms in pancreatic B-cells. PMID- 2185069 TI - The fuel concept for insulin release: regulation of glucose phosphorylation in pancreatic islets. PMID- 2185070 TI - ATP-sensitive K+ channels: a link between B-cell metabolism and insulin secretion. PMID- 2185071 TI - Cytoplasmic calcium ions and other signalling events in insulin secretion. PMID- 2185072 TI - Protein kinase C and the regulation of insulin secretion. PMID- 2185073 TI - Protein phosphorylation in the regulation of insulin secretion and biosynthesis. PMID- 2185074 TI - Mechanisms of action of entero-insular hormones and neural input on the insulin secretory process. PMID- 2185075 TI - Biosynthesis and storage of insulin. PMID- 2185076 TI - The cytochrome P450 IV family: constitutive and inducible haemoproteins. PMID- 2185077 TI - Cytochrome P-450 and oxidative metabolism in invertebrates. PMID- 2185078 TI - Structure, function and regulation of cytochrome P-450 forms in fish. PMID- 2185079 TI - Molecular genetics of the human cytochrome P-450 system. PMID- 2185080 TI - Role of hormones in the control of mixed-function oxidases. PMID- 2185081 TI - Molecular mechanisms of cytochrome P-450 gene regulation. PMID- 2185082 TI - Induction of cytochrome P 450 I and its influences in chemical carcinogenesis. PMID- 2185083 TI - Future developments with the cytochromes P-450: promises for the applied chemical and medical sciences. PMID- 2185084 TI - Inhibition of squalene epoxidase and sterol side-chain methylation by allylamines. PMID- 2185085 TI - Inhibitors of 2,3-oxidosqualene lanosterol-cyclase as potential antifungal agents. PMID- 2185086 TI - Inhibition of sterol biosynthesis enzymes in vitro by analogues of high-energy carbocationic intermediates. PMID- 2185087 TI - Plant sterol biosynthesis inhibitors: the 14-demethylation steps, their enzymology and inhibition. PMID- 2185088 TI - Mutation in cytochrome P-450-dependent 14 alpha-demethylase results in decreased affinity for azole antifungals. PMID- 2185089 TI - Inhibition of the sterol delta 14-reductase and delta 8----delta 7-isomerase in fungi. PMID- 2185090 TI - Inhibitors of ergosterol biosynthesis as crop protection agents. PMID- 2185091 TI - Application of sterol synthesis inhibitors to investigate the sterol requirements of protozoa and plants. PMID- 2185092 TI - Signal transduction mechanisms in cancer. PMID- 2185093 TI - Evolution of the P450 gene superfamily and regulation of the murine Cyp1a1 gene. PMID- 2185094 TI - Metabolic control of oncogene expression. PMID- 2185095 TI - Metabolic strategies in cancer chemotherapy. PMID- 2185096 TI - Application of metabolic-control logic to the requirements for cell division. PMID- 2185097 TI - Tumour-host metabolic interrelationships. PMID- 2185098 TI - Protein targeting to peroxisomes. PMID- 2185099 TI - The peroxisome: functional properties in health and disease. PMID- 2185100 TI - Liver growth and early cellular changes in response to peroxisome proliferation. PMID- 2185101 TI - Carcinogenicity of peroxisome proliferators: evaluation and mechanisms. PMID- 2185102 TI - Hepatic peroxisome proliferation and oxidative stress. PMID- 2185103 TI - Induction of cytochrome P-450 IVA 1-mediated fatty acid hydroxylation: relevance to peroxisome proliferation. PMID- 2185104 TI - Glucokinase gene structure. Functional implications of molecular genetic studies. AB - Glucokinase is expressed in both the liver and the pancreatic beta-cell and plays a key role in the metabolism of glucose by both tissues. Expression of this enzyme is differentially regulated; hepatic glucokinase is stimulated by insulin and repressed by cAMP, whereas beta-cell glucokinase activity is increased by glucose. Recently, the glucokinase gene has been characterized and was found to contain two different transcription control regions. One region regulates transcription of the gene in the liver, whereas the other region, which lies at least 12 kilobases further upstream, controls transcription in the pancreatic beta-cell. The finding of two different transcription control regions in a single glucokinase gene provides a genetic basis for the tissue-specific differential regulation of glucokinase and will serve as the basis for further studies to identify and characterize the different regulatory elements and factors in the liver and beta-cell, which are presumably involved. Comparison of different glucokinase cDNAs isolated from hepatic, insulinoma, and islet cDNA libraries indicates that at least three glucokinase isoforms are generated by differential RNA processing of the glucokinase gene transcripts. Whether any of these glucokinase isoforms are functionally unique remains to be determined. PMID- 2185106 TI - Nonprogression of subclinical beta-cell dysfunction among first-degree relatives of IDDM patients. 5-yr follow-up of the Seattle Family Study. AB - It is unknown among first-degree relatives of individuals with insulin-dependent diabetes mellitus (IDDM) whether the disease process occurs in relatively few but always progresses to clinical IDDM or whether subclinical disease is more common but remains nonprogressive in many cases. Islet cell antibodies (ICAs) were found in 21 of 724 (2.9%) first-degree relatives during screening in the greater Seattle area between 1983 and 1988. Measures of beta-cell function (glucose disappearance rate [Kg], fasting insulin, acute insulin response to intravenous arginine [AIRarg], acute insulin response to intravenous glucose [AIRgluc], slope of glucose potentiation of AIRarg) and insulin sensitivity were obtained. Twenty individuals, 9 ICA+ relatives and 11 ICA- relatives, were evaluated prospectively. When expressed in relation to the expected AIRgluc based on each subject's sensitivity index, AIRgluc in 18 of 20 relatives fell below 100%, indicating inappropriately low insulin secretion (subclinical beta-cell dysfunction). After a median follow-up of 42 mo, 10 of 11 ICA- relatives remained ICA-. None showed deteriorating beta-cell dysfunction, and none developed diabetes. Five ICA+ relatives showed persistent immunologic positivity. beta-Cell function remained remarkably stable in all except 2 relatives. One was a 15-yr old boy who developed IDDM shortly after screening and before evaluation of beta cell function could be carried out. The other was an 18-yr-old monozygotic twin who developed IDDM after 27 mo. Both of these individuals had ICAs of 80 Juvenile Diabetes Foundation U and had been discordant for less than 5 yr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185105 TI - Systemic venous drainage of pancreas allografts as independent cause of hyperinsulinemia in type I diabetic recipients. AB - To evaluate the metabolic consequences of pancreas transplantation with systemic venous drainage on beta-cell function, we examined insulin and C-peptide responses to glucose and arginine in type I (insulin-dependent) diabetic pancreas recipients (n = 30), nondiabetic kidney recipients (n = 8), and nondiabetic control subjects (n = 28). Basal insulin levels were 66 +/- 5 pM in control subjects, 204 +/- 18 pM in pancreas recipients (P less than 0.0001 vs. control), and 77 +/- 17 pM in kidney recipients. Acute insulin responses to glucose were 416 +/- 44 pM in control subjects, 763 +/- 91 pM in pancreas recipients (P less than 0.01 vs. control), and 589 +/- 113 pM in kidney recipients (NS vs. control). Basal and stimulated insulin levels in two pancreas recipients with portal venous drainage were normal. Integrated acute C-peptide responses were not statistically different (25.3 +/- 4.3 nM/min in pancreas recipients, 34.2 +/- 5.5 nM/min in kidney recipients, and 23.7 +/- 2.1 nM/min in control subjects). Similar insulin and C-peptide results were obtained with arginine stimulation, and both basal and glucose-stimulated insulin-C-peptide ratios in pancreas recipients were significantly greater than in control subjects. We conclude that recipients of pancreas allografts with systemic venous drainage have elevated basal and stimulated insulin levels and that these alterations are primarily due to alterations of first-pass hepatic insulin clearance, although insulin resistance secondary to immunosuppressive therapy (including prednisone) probably plays a contributing role. To avoid hyperinsulinemia and its possible long-term adverse consequences, transplantation of pancreas allografts into sites with portal rather than systemic venous drainage should be considered. PMID- 2185107 TI - Application of HPLC in disposition study of A14-125I-labeled insulin in mice. AB - To describe quantitatively the in vivo distribution and elimination of insulin, high-performance liquid chromatography (HPLC) separation was applied to the pharmacokinetic study of human insulin labeled with 125I at tyrosine A14 (A14 125I-insulin) as a tracer. Intact A14-125I-insulin levels were determined by HPLC and trichloroacetic acid (TCA) precipitation in plasma and various tissues after its intravenous bolus injection into mice. TCA precipitation consistently overestimated the intactness of A14-125I-insulin compared with HPLC, possibly due to the presence of both a TCA-precipitable intermediate degradation product of labeled insulin found in HPLC elution profiles and reported high-molecular-weight forms of labeled insulin in plasma. Thus, TCA precipitation gave a considerably lower total plasma clearance (Cltot) value than HPLC. The half-life of A14-125I insulin was prolonged by a simultaneous injection of 8 U/kg unlabeled insulin, and labeled insulin behaved similarly to [14C]inulin (an extracellular fluid marker). The concentration time profiles of HPLC-separated labeled insulin in plasma were analyzed by a noncompartmental moment method, and both Cltot and steady-state apparent volume distribution (VDss) of A14-125I-insulin were considerably decreased by unlabeled insulin coadministration. In particular, VDss of labeled insulin decreased by 79%, similar to that of inulin (181 ml/kg), suggesting that the nonspecific binding of labeled insulin to tissues was so small that VDss of labeled insulin was reduced to the extracellular fluid volume (approximately 20% of the body weight) when its receptor binding was blocked effectively by unlabeled insulin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185109 TI - Increased basal glucose production and utilization in nondiabetic first-degree relatives of patients with NIDDM. AB - To characterize the abnormalities in basal glucose homeostasis in people who are at increased risk for non-insulin-dependent diabetes mellitus (NIDDM), we measured the rates of basal hepatic glucose output (HGO), glucose disappearance, and metabolic clearance of glucose (MCR) in 27 nondiabetic first-degree relatives of NIDDM patients and 16 age-, sex-, and weight-matched healthy control subjects with no family history of NIDDM. Mean fasting plasma glucose was significantly lower (P less than 0.05) in control subjects (mean +/- SE 77 +/- 2 mg/dl) than in relatives (84 +/- 2 mg/dl). Mean basal insulin levels were not significantly different between relatives and control subjects (10.0 +/- 1.5 vs. 7.7 +/- 1.0 microU/ml). Mean basal HGO was significantly lower in control subjects compared with relatives (1.83 +/- 0.07 vs. 2.20 +/- 0.10 mg.kg-1.min-1, P less than 0.05). Mean MCR was similar in relatives (2.58 +/- 0.12 mg.kg-1.min-1) and control subjects (2.35 +/- 0.09 mg.kg-1.min-1). In summary, this study demonstrates that basal hepatic glucose production and glucose utilization are increased in glucose tolerant first-degree relatives compared with healthy control subjects. We conclude that impaired basal hepatic glucose regulation rather than glucose disposal is present as an early defect in glucose-tolerant first-degree relatives of NIDDM patients. PMID- 2185108 TI - Free-fatty acid inhibition of insulin binding, degradation, and action in isolated rat hepatocytes. AB - The effect of free fatty acids (FFAs) on insulin binding and action was investigated in isolated rat hepatocytes. Oleic acid (0.4 mM) added to the cells rapidly (within 45 min) reduced insulin binding and degradation (each by 45%; P less than 0.001, n = 7) without changing the apparent receptor affinity. The effect was concentration dependent; a half-maximal inhibitory effect occurred at 0.150 +/- 0.050 mM (mean +/- SE). Oleic acid exerted no effect on insulin binding in energy-depleted (KCN-treated) cells. Oleic, palmitic, stearic, palmitoleic, and eicosapentaenoic acids were equally effective in reducing insulin binding. FFA did not change insulin binding to partially purified insulin receptors, thus excluding a direct effect on the insulin receptor. Furthermore, binding to partially purified receptors from solubilized cells pretreated with 0.2 mM oleic acid was not changed, indicating the effect of FFA in intact cells is on the rate of receptor internalization and/or recycling. Concomitant with the effect on insulin binding, oleic acid elicited a concentration-dependent reduction in nonstimulated cellular [14C]aminoisobutyric acid uptake (AIB; 29 +/- 8%, P less than 0.05) and decreased the maximal effect of insulin (39 +/- 7%, P less than 0.05). Thus, in a concentration-dependent manner, different fatty acids can reduce the number of binding sites for insulin and the degradation of insulin by isolated liver cells. Basal and insulin-stimulated AIB transport was reduced, suggesting the presence of postbinding perturbations. These data suggest that FFA exerts an important modulating effect on insulin action in the liver. PMID- 2185110 TI - Diabetic glycemic control and retinal blood flow. AB - The effect of strict glycemic control on retinal volumetric blood flow rate (Q) was investigated in 13 insulin-dependent diabetic patients with laser Doppler velocimetry and monochromatic fundus photography. Strict glycemic control was achieved by glucose monitoring and four daily insulin injections. Q was determined in a major retinal vein at baseline and then 5 days, 2 mo, and 6 mo after the institution of strict control. Level of retinopathy was assessed from stereocolor fundus photographs taken at baseline and 6 mo. After 6 mo of strict diabetic control, five eyes demonstrated progression (P) by one or more retinopathy levels, and eight eyes showed no progression (NP). At 5 days, there was a significant decrease in Q of 1.4 +/- 0.9 microliters/min (P less than 0.005) in NP eyes and a nonsignificant increase in Q of 1.2 +/- 1.7 microliters/min in P eyes. Changes in Q from baseline observed at 5 days were strongly correlated with changes in retinopathy level at 6 mo (r = 0.79, P less than 0.005). No significant changes in Q from baseline were observed at 2 and 6 mo. A lack of decrease in Q at 5 days was associated with the progression of retinopathy that occurs in some patients after the institution of strict glycemic control and may serve as a predictor for progression of retinopathy. PMID- 2185111 TI - Decreased VIP content in peripheral nerve from streptozocin-induced diabetic rats. AB - After induction of diabetes with streptozocin (STZ-D) in rats, we measured vasoactive intestinal polypeptide (VIP) content in sciatic nerve and spinal cord obtained from nondiabetic, untreated STZ-D, and insulin-treated STZ-D rats. Eight weeks after the onset of diabetes, caudal nerve conduction velocity (NCV) in the untreated STZ-D rats (n = 13) was slower than in the controls (n = 11; mean +/- SE 30.9 +/- 0.6 vs. 41.4 +/- 1.8 m/s, P less than 0.001). The decrease in NCV was less marked in the insulin-treated STZ-D rats (n = 11; 36.3 +/- 0.9 m/s, P less than 0.05 vs. control). VIP content in sciatic nerve decreased in the untreated STZ-D rats (1.33 +/- 0.23 ng/g wet wt) compared with the other groups (control, 3.10 +/- 0.44, P less than 0.01; insulin-treated STZ-D, 2.44 +/- 0.55, P less than 0.05). However, in spinal cord, VIP content was not significantly different among the three groups. The VIP levels in sciatic nerve showed a positive correlation with NCV (r = 0.430, P less than 0.01). In addition, an inverse correlation between VIP levels and blood glucose levels was observed (r = 0.5624, P less than 0.001). NCV was also inversely correlated with blood glucose levels (r = -0.7662, P less than 0.001). Together with a previous morphological study, these findings suggest a possible causal relationship between reduced VIP content and diabetic neuropathy. PMID- 2185112 TI - Evidence of cosecretion of islet amyloid polypeptide and insulin by beta-cells. AB - Islet amyloid polypeptide (IAPP) has been identified as the major constituent of the pancreatic amyloid of non-insulin-dependent diabetes mellitus (NIDDM) and is also present in normal beta-cell secretory granules. To determine whether IAPP is a pancreatic secretory product, we measured the quantity of IAPP-like immunoreactivity (IAPP-LI), insulin, and glucagon released into 5 ml of incubation medium during a 2-h incubation of monolayer cultures (n = 5) of neonatal (3- to 5-day-old) Sprague-Dawley rat pancreases under three conditions: 1.67 mM glucose, 16.7 mM glucose, and 16.7 mM glucose plus 10 mM arginine and 0.1 mM isobutylmethylxanthine (IBMX). The quantity of IAPP-LI, insulin, and glucagon in the cell extract was also determined. Mean +/- SE IAPP-LI in the incubation medium increased from 0.041 +/- 0.003 pmol in 1.67 mM glucose to 0.168 +/- 0.029 pmol in 16.7 mM glucose (P less than 0.05) and 1.02 +/- 0.06 pmol in 16.7 mM glucose plus arginine and IBMX (P less than 0.05 vs. 1.67 or 16.7 mM glucose). Insulin secretion increased similarly from 4.34 +/- 0.27 to 20.2 +/- 0.6 pmol (P less than 0.05) and then to 135 +/- 5 pmol (P less than 0.05 vs. 1.67 or 16.7 mM glucose). Glucagon release tended to decrease with the increase in glucose concentration (0.39 +/- 0.01 vs. 0.33 +/- 0.02 pmol, P less than 0.1), whereas with the addition of arginine and IBMX to high glucose, glucagon release increased to 1.32 +/- 0.03 pmol (P less than 0.05 vs. 1.67 or 16.7 mM glucose).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185113 TI - Dandy-Walker syndrome and agenesis of the cerebellar vermis: diagnostic problems and genetic counselling. PMID- 2185114 TI - Ultrasound measurement of urine volume of children with neurogenic bladder. AB - This study assessed the accuracy and precision of a portable ultrasound unit which computes bladder volume after scans are made in the sagittal and transverse planes. 39 ultrasound measures were made on 20 children between the ages of one month and 16 years, and these measures were then compared with catheterized volumes. The mean difference of ultrasound minus true volume was 6.9 ml (SD 32ml). The ultrasound scanner was found to be accurate, inexpensive and easy to use for measuring post-voiding residual urine volumes in children with neurogenic bladder. PMID- 2185115 TI - Periventricular leukomalacia: ultrasonic and neuropathological correlations. AB - Ultrasound scans of a preterm neonate (27 weeks gestation) at seven weeks of age showed periventricular echo-free cavities, but these were no longer visible at 15 weeks, three weeks before the infant died. At autopsy, a linear glial scar, extending from the periventricular white-matter into the white axis of the parasagittal gyrus, was found in the area occupied by the periventricular cysts. The larger cavity was reduced to a slit-like excavation in the midst of glial tissue. Unsuspected focal infarcts in the cerebral cortex were also found. This observation demonstrates that transient echo-free cavities represent foci of cystic necrosis, which are subject to secondary collapse. In the authors' experience, the linear extension of periventricular leukomalacia (PVL) into the core of parasagittal gyri is a frequent feature of PVL, and one which cannot easily be accounted for by the usual explanations of border-zone ischaemic softening. PMID- 2185116 TI - [Hematopoietic stem cells: stochastic differentiation and humoral control of their proliferation]. PMID- 2185117 TI - Anticonvulsant actions of phencyclidine receptor ligands: correlation with N methylaspartate antagonism in vivo. AB - 1. Drugs with phencyclidine (PCP)-like activity in behavioural discrimination and [3H]PCP binding studies share anticonvulsant properties. 2. We have compared the rank order potency of a series of PCP-like compounds as N-methylaspartate (NMA) antagonists, determined from previously published studies from our laboratory, with their rank order anticonvulsant potencies as determined by two independent research groups in three different in vivo models of experimentally-induced epilepsy. 3. Rank order potency for NMA antagonism correlated well with rank order anticonvulsant potency. Furthermore, the systemic doses required for an effective blockade of NMA-evoked excitations were, in most cases, similar to those which produced anticonvulsant activity. 4. The results suggest that functional NMA antagonism may underlie the shared anticonvulsant properties of structurally dissimilar compounds with PCP-like activity. PMID- 2185118 TI - Interactions between analgesics and calcium channel blockers. AB - 1. The findings, derived from different experimental models, examined in this review, provide evidence that the calcium channel blockers and related drugs possess analgesic effects. 2. The antinociceptive action that some analgesic drugs exhibit may be related to calcium channel blockade. 3. Evidence from a variety of biochemical and pharmacological experimental approaches, support the existence of an interelation between the calcium modulators and the opioid drugs. 4. This idea agrees with the novel neuropharmacological hypothesis that a common very high affinity binding site for multiple neurotransmitters could exist, as has been proposed by Pasternak and Wood (1986). 5. This hypothesis could be extended to the neuromodulators or other neuromediators. PMID- 2185119 TI - Contractile responses of the human urinary bladder, renal pelvis and renal artery to endothelins and sarafotoxin S6b. AB - 1. Endothelin-1 (ET-1), endothelin-3 (ET-3) and sarafotoxin S6b (SRFTX) produced a concentration-dependent tonic contraction of the human isolated urinary bladder, renal pelvis and renal artery with threshold at nM concentration. 2. In the bladder, the following order of potency was found: ET-1 greater than SRFTX greater than ET-3. In the renal pelvis, all peptides displayed similar affinity but, at high concentrations the maximal response was highest for SRFTX followed by ET-1 and ET-3. In the renal artery ET-1 and SRFTX were about equipotent and equieffective while ET-3 produced only a slight and inconsistent (2 out of 5 cases) vasoconstrictor response. 3. As shown previously for the human bladder muscle, the response to ET-1 in the renal pelvis was nifedipine (1 microM) resistant while a consistent fraction of the response was blocked by nifedipine in the human renal artery. 4. These findings indicate that peptides of the endothelin family exert a potent contractile effect on various human smooth muscles. Participation of dihydropyridine- and voltage-sensitive calcium channels in the contractile response produced by these peptides may vary from one organ to another. PMID- 2185120 TI - A rapid and sensitive ELISA for rainbow trout maturational gonadotropin (tGtH II): validation on biological samples; in vivo and in vitro responses to GnRH. AB - A rapid and sensitive heterologous enzyme-linked immunosorbent assay (ELISA) was developed to measure rainbow trout maturational gonadotropin. Purified salmon maturational gonadotropin (sGtH II) was used as reference hormone. Optimization of the procedure was performed by using an anti-beta sGtH serum. Two procedures were developed: an equilibrium assay (which did not involve a preincubation step) which lasted for 8 hr and a nonequilibrium assay (which involved a preincubation step) which lasted for 26 hr. The nonequilibrium assay gave the best sensitivity (70 pg/ml sample). GtH II measurements on in vivo and in vitro samples from GnRH analogs or sGnRH experiments showed that the ELISA procedure could be used over a wide range of concentrations. The method was validated by comparing GtH II concentrations measured by both RIA and ELISA. PMID- 2185121 TI - Localization of insulin to gastroenteropancreatic cells in the turtle gastrointestinal tract. AB - Insulin has been localized immunocytochemically to open-type gastroenteropancreatic endocrine cells in sections of Bouin's-fixed upper, middle, and lower intestine from Chrysemys picta, Pseudemys scripta scripta, P. scripta elegans, P. floridana, Sternotherus odoratus, and Trionyx spinifer asper. Radioimmunoassay of extracts of mucosal scrapings from Chrysemys intestine indicates differential amounts of insulin-like immunoreactivity within the intestine (higher amounts in the lower intestine) and in concentrations approximately one-tenth to one-fifth that found in extracts of Chrysemys pancreas. The presence of insulin in the gastrointestinal tract of chelonians represents a major departure from the typical vertebrate condition which is characterized by an absence of insulin from the spectrum of regulatory peptides in the gut. PMID- 2185122 TI - Maturation of the endocrine pancreas in the sea bass, Dicentrarchus labrax L. (Teleostei): an immunocytochemical and ultrastructural study. I. Glucagon producing cells. AB - The structure of the endocrine pancreas in the sea bass (Dicentrarchus labrax L.) was studied with special reference to glucagon-immunoreactive cells. As described in most of the teleosts, the sea bass was found to have a diffuse pancreas. In the adult, endocrine cells were clustered in a principal islet and numerous accessory islets where the glucagon A cells were localized peripherally. Under electron microscopy, the A cells displayed a clear hyaloplasm with granules having typical spherical or polyhedral cores, as in other vertebrates. The maturation of the endocrine pancreas was monitored under rearing conditions. The endocrine pancreas appeared during the prelarval stage, 3 days after hatching, and consisted of a single cluster of morphologically similar cells, containing very small cytoplasmic granules. During the larval stage, cytodifferentiation resulted in modifications of cell shape and increased granule size. Typical granules appeared in 8-mm-long larvae. Cells immunoreactive with mammalian glucagon antibodies appeared only at the beginning of the juvenile stage (3 months/20 mm). Electron microscope observations revealed that the storage of hormone in numerous cytoplasmic granules began at this stage. PMID- 2185123 TI - Increased vascular permeability, erythema, and leukocyte emigration induced in rabbit skin by streptococcal erythrogenic toxin type A. AB - A highly purified streptococcal erythrogenic toxin type-A (SET-A) caused increased vascular permeability, erythema, and leukocyte emigration when injected into the skin of rabbits. A blueing reaction indicating increased vascular permeability appeared at 1 h, reaching the highest intensity between 4 and 5 h, decreasing thereafter and completely disappearing at 12 h after toxin injection. The intensity of the increase in permeability was found to be dose dependent. The erythematous reaction began later and persisted longer than the blueing. The time course of leukocyte emigration was found roughly to parallel that of the blueing reaction. The skin reaction to SET-A in rabbits can be characterized as having an acute non-specific exudative inflammatory nature. PMID- 2185124 TI - Regulation of breakdown of canavanyl proteins in Escherichia coli by growth conditions in lon+ and lon- cells. AB - In vivo rates of proteolysis of canavanyl proteins were compared in lon+ and lon- Escherichia coli strains following growth in a variety of media. Both lon+ and lon- cells grown rapidly in complex media possessed higher levels of constitutive degradative activity than when cultured in minimal media. Pre-growth of lon+ cells in the presence of canavanine induced proteolytic activity following growth in minimal media as did stress agents such as heat, alcohol and puromycin: the lon mutant did not show the increased activity following canavanine treatment. The results suggest the presence of a proteolytic activity which selectively degrades aberrant proteins which does not involve protease La, the product of the lon gene, and which furthermore is regulated in part by growth conditions independently of the stress response. PMID- 2185125 TI - Elimination of ColE1 group (pBR322 and pBR329) plasmids in Escherichia coli by alpha-santonin. AB - alpha-Santonin, a compound extracted from the flower heads of Arthemisia maritima plant, was effective in elimination of small, multicopy, relaxed plasmids (pBR322 and pBR329 with CoLE1 origin of replication in Escherichia coli, whereas plasmids of IncF1, H1 and X group were totally refractory under similar conditions, suggesting that this agent was specific in curing the CoLE1 group of plasmids. PMID- 2185126 TI - NMR studies of a bacterial cell culture medium (LB broth): cyclic nucleotides in yeast extracts. AB - The composition of LB broth (tryptone, yeast extract and NaCl) was investigated by 1H,31P-NMR spectroscopy, FPLC and gel electrophoresis. An unexpected finding was the high level of 2'3'-cyclic nucleotides, detected by characteristic 31P-NMR resonances in the region 20-21 ppm, originating from the yeast component. 31P-NMR resonances for cyclic nucleotides were observed during the autolysis of Saccharomyces cerevisiae cells, and in model reactions of RNase with RNA. PMID- 2185127 TI - High level expression in Escherichia coli of a fungal gene under the control of strong promoters. AB - A recent report (Patino et al., (1989) FEMS Microbiol. Lett. 58, 139-144) described the low level expression, in Escherichia coli, of the Isopenicillin N Synthase (IPNS) gene from Cephalosporium acremonium under the control of strong promoters. We report here our work on the expression of the IPNS gene. Plasmids containing the IPNS gene under the control of the trp or trc promoters directed synthesis of high levels of active IPNS in E. coli. Constitutive and inductive high level IPNS expression systems have been developed. Importantly, the expression vectors do not encode beta-lactamase so IPNS activity can be determined directly by biological assays. Analysis by nmr verified that the IPNS produced from these expression systems catalysed the conversion of delta-(L-alpha aminoadipoyl)-L-cysteinyl-D-valine (LLD-ACV) to isopenicillin N in high yield. PMID- 2185128 TI - Macrophage hyperreactivity to endotoxin induced by streptococcal pyrogenic exotoxin in rabbits. AB - Pretreatment of rabbits with streptococcal pyrogenic exotoxin (SPE) resulted in an enhancement of their febrile response to subsequent endotoxin challenge. This suggested that SPE may enhance the macrophage capacity to respond to endotoxin in vivo to produce an endogenous pyrogen. It was also demonstrated that peritoneal macrophages derived from SPE-treated rabbits exhibited hyperreactivity to endotoxin in vitro as assessed by endotoxin-induced increase in glucose consumption. These data indicate that SPE has the ability to enhance macrophage reactivity to endotoxin. PMID- 2185129 TI - A bifunctional Streptomyces-E. coli promoter-probe vector. AB - A bifunctional Streptomyces-E. coli promoter probe vector, pULJA30, has been developed to isolate and characterize nucleotide sequences involved in transcription initiation and regulation. The vector is derived from plasmid pIJ486, carries the pIJ101 replicon and utilizes the promoterless aminoglycoside phosphotransferase (neo) as indicator gene. Important features of the new vector include: wide Streptomyces host range and as high a plasmid copy number as the parental pIJ486, an upstream transcriptional terminator (toop) and a polylinker sequence with unique sites for BamHI and BglII for flexible cloning, fragment re isolation and direct sequencing of promoter-active inserts. pULJA30 also has an E. coli replicon (from pBR322) and the possibility of selection in Streptomyces and E. coli by using the tsr, neo and bla genes, which makes it very convenient to test the comparative functionality of Streptomyces promoters in E. coli. PMID- 2185130 TI - Conjugational cotransfer of IncFI and IncI conjugative plasmids forming aggregate in a pathogenic Citrobacter freundii strain. AB - Two plasmids, pEM4 (IncFI) determining virulence and pEM6 (IncI) determining colicine I production and resistance to tetracycline, have been found in a pathogenic strain of Citrobacter freundii. Even though pEM4 and pEM6 plasmids are conjugative and transfer themselves very efficiently during conjugation, a high cotransfer of both plasmids is observed--an unusually high fraction of transconjugants acquiring pEM6 acquires pEM4 and vice versa. The observed cotransfer of these plasmids is connected with their ability to complement their conjugational functions. An insertion mutant of pEM4 with decreased frequency of conjugational transfer has been isolated. This mutant (pEM44) lost its ability to mobilize nonconjugative plasmids. Its transfer is stimulated by pEM6 and it is transferred from (pEM44, pEM6) donors almost exclusively with pEM6 plasmid. The role of cotransfer and stimulation phenomena in spreading of plasmid aggregates in bacterial population is discussed. PMID- 2185131 TI - Cloning of the ethidium efflux gene from Escherichia coli. AB - The gene specifying the ethidium efflux system of Escherichia coli has been cloned on a 3.2 kbp HindIII fragment and located on a 1.2 kbp fragment within this. Cross-resistance studies indicate that the system has a broad specificity for monovalent cations and the gene shows no hybridisation with similar genes found in Staphylococci. PMID- 2185132 TI - Variable conservation of nucleolus organizer regions during karyotypic evolution in Microtidae. AB - The location of the nucleolus organizer regions (NORs) was studied in four species of Microtidae (Microtus nivalis, M. cabrerae, M. arvalis, and Arvicola sapidus). The comparative study of these locations shows that some NORs have been conserved despite the chromosome rearrangements that have occurred through karyotypic evolution, while others have been lost. In addition, there are many chromosomes in which NORs seem to have appeared or been lost without apparent relation to the chromosome rearrangements. Some hypotheses regarding these facts are discussed in the text. PMID- 2185133 TI - Specificity of Escherichia coli mutD and mutL mutator strains. AB - The products of the mutD and mutL genes of Escherichia coli are involved in proofreading by DNA polymerase III and DNA adenine MTase (Dam)-dependent mismatch repair, respectively. We have used the plasmid-borne bacteriophage P22 mnt gene as a target to determine the types of mutations produced in mutL25 and mutD5 strains. Of 60 mutations identified from mutL25 cells, 52 were transition mutations and of these the AT----GC subset predominated (40 out of 52). The majority of AT----GC mutations were found at the same three sites (hotspots). In contrast, transversion mutations (47 out of 76) were found about twice as frequently as transitions (28 out of 76) from mutD5 bacteria. Two hotspots were identified but at different sites than those in the mutL25 cells. These results suggest that the proofreading function of DNA polymerase III primarily repairs potential transversion mutations while Dam-dependent mismatch repair rectifies potential transition mutations. PMID- 2185134 TI - Characterization of the genetic determinants of SsoII-restriction endonuclease and modification methyltransferase. AB - The genes encoding SsoI and SsoII restriction endonuclease (ENase) and methyltransferase (MTase) are located on the small plasmids P6 and P4, respectively, of Shigella sonnei strain 47. Functions provided by plasmids P5, P7 and P9, which include colicinogenicity and immunity to colicin E1, resistance to streptomycin (Sm), and conjugative DNA transfer, respectively, have also been identified. The genes of the SsoII restriction-modification (R-M) system have been cloned into Escherichia coli expressing the 35-kDa (ENase) and 43-kDa (MTase) products. A restriction map of the P4 plasmid DNA was determined, and the approximate location of the genes encoding SsoII ENase and MTase (ssoIIR and ssoIIM) on that have been established. SsoI is an isoschisomer of EcoRI and SsoII cleaves the 5'-/CCNGG/recognition sequence producing 5'-protruding 5-nt long cohesive ends. PMID- 2185135 TI - Promoter elements and regulation of expression of the cysD gene of Escherichia coli K-12. AB - The cysD gene, involved in cysteine biosynthesis in Escherichia coli and Salmonella typhimurium, is positively regulated by the CysB regulatory protein. The cysD promoter of E. coli K-12 in a 492-bp PstI-Eco RI fragment was sequenced. The in vivo transcription start point (tsp) for the cysD gene was determined by the methods of T4 DNA polymerase mapping and mung-bean nuclease mapping. The -10 region of the cysD promoter (TATAGT) is closely homologous to the -10 consensus sequence (TATAAT) for E. coli promoters. The -35 region of this promoter (TTCATT) is less closely related to the -35 consensus sequence (TTGACA). Several mutants were obtained by using a chain-termination method for generating unidirectional deletions. Evidence is presented for a possible CysB protein binding site around 89, thought to be involved in regulation of expression of the cysD gene. PMID- 2185136 TI - Expression of Agrobacterium rhizogenes rolB gene fusions in Escherichia coli: production of antibodies against the RolB protein. AB - Expression of the rolB gene of Agrobacterium rhizogenes TL-DNA is sufficient to trigger root differentiation in transformed plant cells. To investigate the role of RolB in differentiation, a large portion of rolB, comprising about 90% of its C-terminal coding sequence, was cloned into vectors pEX34 and pEA305 in frame with the truncated N termini of the pL-MS2 phage DNA polymerase and, respectively, the ptac-c Its phage lambda repressor gene. Hybrid proteins were expressed from both fusions and the one from pMTBEX1 was utilized to raise antibodies. These antibodies specifically recognize the RolB moiety in both pL MS2-rolB and ptac-cI-rolB fusions. Unfused, complete RolB protein was obtained by in vitro translation in a rabbit reticulocyte system of a transcript obtained by in vitro transcription of rolB. RolB protein is specifically immunoprecipitated by the antibodies raised against the hybrid protein MS2-RolB. PMID- 2185137 TI - Nucleotide sequence of the metH gene of Escherichia coli K-12 and comparison with that of Salmonella typhimurium LT2. AB - The Escherichia coli K-12 metH gene, encoding the vitamin B12-dependent homocysteine transmethylase, is located between iclR and lysC in the 91-min region of the chromosome. The metH gene has been sequenced and reveals an open reading frame of 3600 bp encoding a polypeptide of 1200 amino acids (aa) with a calculated Mr of 132 628. The first 414 aa of the deduced polypeptide sequence are 92% identical to the 414 aa deduced from the partially sequenced Salmonella typhimurium LT2 metH gene. In-frame fusions of metH to lacZ were used to confirm the reading frame of the metH gene and to study its regulation. metH was repressed tenfold, presumably indirectly, by L-methionine and the metJ gene product, while vitamin B12 did not induce de novo synthesis of MetH. PMID- 2185138 TI - The nifH promoter region of Rhizobium leguminosarum: nucleotide sequence and promoter elements controlling activation by NifA protein. AB - The nucleotide (nt) sequence of the Rhizobium leguminosarum nifH promoter region contains a consensus promoter, a consensus upstream activator sequence (UAS), a pseudo (psi) promoter and a psi UAS. We mapped the transcription start point for the consensus promoter sequence by primer extension. This promoter differs from the consensus in one of the four supposedly invariant nt and can be activated by the Klebsiella pneumoniae nifA product in Escherichia coli. Under these conditions the psi promoter and psi UAS do not function. A low-copy-number plasmid construct containing the psi UAS as well as the consensus UAS delayed the onset of symbiotic nitrogen fixation in nodules induced on Pisum sativum. Studies of high-copy-number nifH promoter constructs showed that partial deletion of the consensus UAS does not alter the ability to inhibit nitrogen fixation by titration of NifA suggesting that NifA can also complex with RNA polymerase containing the alternative sigma-factor RpoN. PMID- 2185139 TI - Analysis and nucleotide sequence of an origin of DNA replication in Acinetobacter calcoaceticus and its use for Escherichia coli shuttle plasmids. AB - A shuttle plasmid for Acinetobacter calcoaceticus and Escherichia coli has been constructed from a cryptic A. calcoaceticus lwoffi plasmid and pBR322. It is transformed to A. calcoaceticus BD413 by natural competency, yielding about 10(6) transformants per microgram of plasmid DNA. The ApR and TcR genes of pBR322 are functional in A. calcoaceticus. A gene bank was constructed from chromosomal A. calcoaceticus DNA and the shuttle plasmid. Direct transformation to A. calcoaceticus yielded about 95% recombinants, indicating a sixfold enrichment of recombinant plasmids compared to E. coli. One clone complementing a trpE mutation carried a 20-kb insertion and transformed with a 30-fold higher efficiency when compared to the vector. A deletion analysis of the shuttle plasmid indicates that 2.2 kb is necessary for autonomous replication and stable maintenance in A. calcoaceticus. No rearrangements of the DNA or loss of plasmids are found in that organism, even in the absence of selective pressure, when this sequence is present. A further insertional inactivation analysis creating lacZ transcriptional fusions suggests that the origin of replication (ori) is contained within about 1350 bp. Analysis of beta-galactosidase production in A. calcoaceticus indicates that only a weak promoter activity is directed out of one end of this ori. Its sequence contains A + T-rich regions, an 18-bp element with nearly perfect palindromic symmetry and eleven repeats of the consensus sequence, AAAAAATAT, eight of which are clustered within 360 bp. However, no open reading frames or significant homologies to other ori were found. PMID- 2185140 TI - Lanosterol 14 alpha-demethylase-encoding gene: systematic analysis of homologous overexpression in Saccharomyces cerevisiae using strong yeast promoters. AB - The Saccharomyces cerevisiae 14DM gene, encoding cytochrome P450 lanosterol 14 alpha-demethylase (14DM), was overexpressed in various S. cerevisiae strains under the control of three strong heterologous yeast transcription promoters (pADC1, pGPD, pPHO5) and under the control of its own promoter. Striking, strain specific differences in 14DM transcription and in 14DM contents have been observed. The relative abundances of 14DM-specific mRNA and protein derived from a series of different expression plasmids were compared. It was found that the inducible PHO5 promoter in combination with the JL745 host led to the highest expression levels. 14DM-specific RNA reached up to 2% of the total cellular mRNA in this strain and approx. 3% of the total soluble yeast-cell protein was determined to be 14DM by quantitative Western blotting. By comparing the abundances of the different fusion transcripts with the transcript originating from the corresponding endogenous gene from which the promoter was derived, it could be concluded that the expression levels of the different 14DM fusion genes were far below the theoretically attainable values. PMID- 2185141 TI - Cloning and characterization of the 2,3-oxidosqualene cyclase-coding gene of Candida albicans. AB - 2,3-Oxidosqualene (OS) cyclase (OSC) catalyzes the conversion of OS to lanosterol, an essential step in the biosynthesis of sterols. The Candida albicans gene (ERG7) encoding OSC was cloned by complementation of a Saccharomyces cerevisiae OSC mutant (erg7). Two different Erg+ clones were isolated that contain a common overlapping region. The minimum region required for complementation was determined to be approx. 3.2 kb and a single 2.7-kb ERG7 transcript was detected. The cloned Candida ERG7 DNA complemented an additional nonconditional erg7 allele and a temperature-sensitive erg7 mutation. OSC activity was restored in the mutants as determined by [14C]acetate incorporation in vivo as well as incorporation in vitro in cell-free extracts using either [14C]isopentenyl pyrophosphate or [3H]OS as substrate. The level of OSC produced from expression of a single copy of the Candida ERG7 sequence was sufficient to allow growth of the S. cerevisiae erg7 mutants in the absence of exogenous ergosterol. These data support the contention that the Candida ERG7 sequence is the structural gene for OSC. PMID- 2185142 TI - Nucleotide sequence of the zucchini yellow mosaic virus capsid-encoding gene and its expression in Escherichia coli. AB - Zucchini yellow mosaic virus (ZYMV) RNA was purified and used as a template for the synthesis of cDNA. A partial restriction map covering 9.4 kb of the ZYMV genome was constructed from three clones designated ZYKS-22, ZYKS-16 and ZYKS-3. Sequencing the 3'-end region of the ZYMV genome indicates the presence of (A)48 chain. This is followed by an untranslated region of 210 nucleotides (nt) and a coding region of 837 nt corresponding to the putative virus coat protein (Cp) gene (cp). The predicted amino acid (aa) sequence of Cp derived from the cDNA showed about 50% to 62% homology with the known aa sequence for Cp of six other potyviruses. A construct of the putative cp was subcloned in frame with the lacZp gene promoter in a Bluescript plasmid and expressed in Escherichia coli cells. The fusion polypeptides (34 and 41 kDa), positively reacted in Western blots with an antiserum prepared against the native virus Cp. PMID- 2185143 TI - Rapid bedside assessment of postoperative confusion in older patients. AB - As the number of elderly patients undergoing surgery increases, postoperative confusion becomes an increasingly encountered problem. Postoperative confusion has long been recognized as a specific entity, but the etiology and risk factors have not been well defined. To make the diagnosis promptly, the physician must maintain a high index of suspicion. This review provides a series of brief mental status tests that can be administered quickly at the bedside and outlines a specific approach to treatment. PMID- 2185144 TI - Free radicals and the etiology of colon cancer. AB - This hypothesis paper reviews diverse evidence suggesting that intracolonic production of oxygen radicals may play a role in carcinogenesis. The hypothesis began to evolve when the author made the chance discovery that 1/10,000 dilutions of feces generated detectable quantities of highly reactive hydroxyl radicals (HO.). The rate of HO. formation, detected using DMSO as a molecular probe, was quite remarkable, corresponding to that which would be produced by over 10,000 rads of gamma irradiation per day, absorbed in the periphery of the fecal mass adjacent to the mucosa. The relatively high concentrations of iron in feces, together with the ability of bile pigments to act as iron chelators that support Fenton chemistry, may very well permit efficient HO. generation from superoxide and hydrogen peroxide produced by bacterial metabolism. Such free radical generation in feces could provide a missing link in our understanding of the etiology of colon cancer: the oxidation of procarcinogens either by fecal HO., or by secondary peroxyl radicals (ROO.) to form active carcinogens or mitogenic tumor promotors. Intracolonic free radical formation may explain the high incidence of cancer in the colon and rectum, compared to other regions of the GI tract, as well as the observed correlations of a higher incidence of colon cancer with red meat in the diet, which increases stool iron, and with excessive fat in the diet, which may increase the fecal content of procarcinogens and bile pigments. PMID- 2185145 TI - Superoxide dismutase and catalase as therapeutic agents for human diseases. A critical review. AB - The list of human and animal diseases for which oxygen radical scavenging therapy is being recommended continues to grow, based primarily on inferential evidence suggesting a potential role for oxygen-derived free radicals in various types of pathophysiology. Some distinct advances in pharmacologic manipulation of protein scavengers have been made which could ultimately greatly enhance the use of these reagents as drugs, as well as some innovative techniques for drug delivery (direct injection via endoscopy, iontophoresis). Unfortunately, most of the therapeutic reports in the literature, almost all of which are based on usage of standard (native) SOD and/or catalase, are still anecdotal and/or uncontrolled. A review of the human disease/treatment literature suggests that further tightening of the scientific design of such trials is still badly needed; hopefully better experimental design will be applied when products such as PEG conjugates or genetically engineered polymers are ready for testing. PMID- 2185146 TI - Psychiatric ethics: entering the 1990s. PMID- 2185147 TI - An overview of chronic pain. AB - Pain is the most common symptom for which patients seek medical advice and treatment, and chronic pain takes a heavy toll in patient suffering and disability, reduced quality of life, and economic costs. Despite the interest in pain management in the last half century, the pathways of pain transmission and the optimal methods of pain management are not fully understood. The authors review selected areas of knowledge about chronic pain and its management, including historical views, the assessment of pain, economic factors and costs, and treatment approaches. PMID- 2185148 TI - Lipids and the kidney. PMID- 2185149 TI - Angiotensin II: a powerful controller of sodium transport in the early proximal tubule. AB - Angiotensin II has recently been shown to exert potent control over sodium and water absorption in the proximal convoluted tubule. This transport stimulation is effected by receptors on both the luminal and basolateral membranes of cells located predominantly in the early, S1 proximal tubule. Angiotensin II increases transport primarily by a Gi protein-mediated reduction in intracellular cyclic adenosine monophosphate, which enhances the affinity of the Na(+)-H+ antiporter. Change in early proximal acidification ultimately causes alteration in the amount of sodium chloride leaving the proximal tubule and entering the urine. These direct tubular transport actions by angiotensin II may participate importantly in various physiological actions of the kidney, including the renal response to change in dietary sodium intake and in extracellular volume, as well as in pathophysiological processes such as hypertension. PMID- 2185150 TI - Hypotensive action of DuP 753, an angiotensin II antagonist, in spontaneously hypertensive rats. Nonpeptide angiotensin II receptor antagonists: X. AB - In conscious 18-21-week-old spontaneously hypertensive rats, DuP 753, a nonpeptide angiotensin II receptor antagonist, given orally at 3 and 10 mg/kg or intravenously at 3, 10, and 30 mg/kg, reduced blood pressure dose dependently. It did not alter heart rate at these doses. At 10 mg/kg i.v., DuP 753 decreased blood pressure significantly for at least 24 hours, suggesting a long duration of the antihypertensive effect. Unlike saralasin, DuP 753 did not cause a transient increase in blood pressure. The acute antihypertensive efficacy of DuP 753 was greater than that of captopril. Our data indicate that, for captopril to reduce blood pressure to a similar extent as that of DuP 753, it would need to be supplemented by a diuretic. DuP 753 did not have an acute diuretic effect. Bilateral nephrectomy, but not inhibition of prostaglandin synthesis, abolished the antihypertensive effect of DuP 753, suggesting that the antihypertensive effect of DuP 753 is dependent on an active renin-angiotensin system. Furthermore, DuP 753 inhibited the pressor response to angiotensin II but not the responses to norepinephrine, vasopressin, and Bay K 8644 (a calcium agonist). As neither DuP 753 nor captopril decreased blood pressure acutely in Wistar-Kyoto normotensive rats, our results suggest that the renin-angiotensin system plays a significant role in the control of blood pressure in spontaneously hypertensive rats. PMID- 2185151 TI - Plasma endothelin levels in hypertension and chronic renal failure. AB - Endothelin-1 is a novel endothelium-derived vasoconstrictive peptide. Using a highly specific and sensitive radioimmunoassay for endothelin-1, plasma levels of immunoreactive endothelin-1 were measured in 32 research subjects with normal renal function (21 normal subjects and 11 patients with essential hypertension), 24 patients with nondialyzed chronic renal failure, and 51 patients undergoing maintenance hemodialysis. Although there was no significant difference in plasma immunoreactive endothelin-1 levels among the three groups, patients with essential hypertension had significantly higher plasma endothelin-1 levels than normal subjects (2.29 +/- 1.09 vs. 1.41 +/- 0.50 pg/ml, p less than 0.025). When nondialyzed and hemodialyzed patients were divided into hypertensive and normotensive groups, the nondialyzed hypertensive group (n = 17) had higher plasma endothelin-1 levels than the comparable normotensive group (n = 7) (3.08 +/- 3.43 vs. 0.73 +/- 0.34 pg/ml, p less than 0.05), and the hemodialyzed hypertensive group (n = 18) had higher plasma endothelin-1 levels than the comparable normotensive group (n = 33) (2.66 +/- 1.92 vs. 1.35 +/- 0.73 pg/ml, p less than 0.005). Plasma atrial natriuretic factor, arginine vasopressin, renin activity, and aldosterone concentration did not show significant differences between hypertensive and normotensive individuals or a correlation with plasma endothelin-1 levels. These data suggest that circulating endothelin-1 may be partly involved in the development or maintenance of hypertension in humans. PMID- 2185152 TI - Effect of insulin on renal sodium handling in hypertensive rats. AB - Spontaneously hypertensive rats have reduced peripheral insulin sensitivity. To determine whether hypertensive rats demonstrate reduced response to the antinatriuretic effect of insulin, urinary sodium excretion was determined in hypertensive and normotensive rats (n = 7 per group) before and during euglycemic insulin administration at two infusion rates (21 milliunits/kg load and 4 milliunits/kg/min or 85 milliunits/kg load and 8 milliunits/kg/min). Hypertensive and normotensive time controls received the vehicle for insulin administration. Mean arterial pressure was greater (p less than 0.05) and inulin clearance was less (p less than 0.05) in hypertensive than normotensive rats before insulin infusion. Baseline fractional sodium excretion was not different between groups. Low dose insulin infusion reduced (p less than 0.05) fractional sodium excretion from 0.81 +/- 0.43% to 0.31 +/- 0.07% in hypertensive rats and from 1.05 +/- 0.37% to 0.47 +/- 0.18% in normotensive rats. High dose insulin infusion reduced (p less than 0.05) fractional sodium excretion from 0.67 +/- 0.22% to 0.21 +/- 0.08% in hypertensive rats and from 0.81 +/- 0.15% to 0.30 +/- 0.09% in normotensive rats. Sodium excretion was unchanged in time controls. The reduction in sodium excretion was similar in both rat groups during low dose and high dose insulin infusions. Mean arterial pressure and inulin clearance were unchanged from baseline values during insulin infusion in all rat groups. Glucose requirement to maintain euglycemia was greater (p less than 0.05) in normotensive than hypertensive rats at both insulin infusion rates. Thus, while hypertensive rats have reduced sensitivity to the hypoglycemic effects of insulin, the antinatriuretic response to insulin is not different from that of normotensive rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185153 TI - Chronic hyperinsulinemia and blood pressure. Interaction with catecholamines? AB - Although hyperinsulinemia and increased adrenergic activity have been postulated to be important factors in obesity-associated hypertension, a cause and effect relation between insulin, catecholamines, and hypertension has not been established. The aim of this study was to determine whether chronic hyperinsulinemia, comparable with that found in obese hypertensive patients, causes hypertension in normal dogs, increases plasma catecholamines, or potentiates the blood pressure effects of norepinephrine. In six normal dogs, insulin infusion (1.0 milliunits/kg/min) for 7 days, with euglycemia maintained, increased fasting insulin fourfold to sixfold. However, mean arterial pressure did not increase, averaging 99 +/- 2 mm Hg during the control period and 91 +/- 3 mm Hg during the 7 days of insulin infusion. Insulin did not alter plasma norepinephrine or epinephrine, which averaged 171 +/- 27 and 71 +/- 14 pg/ml, respectively, during the control period and 188 +/- 29 and 45 +/- 12 pg/ml during the 7 days of insulin infusion. In six dogs, norepinephrine was infused (0.2 microgram/kg/min) for 7 days to raise plasma norepinephrine to 2,940 +/- 103 pg/ml. Insulin infusion (1.0 milliunits/kg/min) for 7 days during simultaneous infusion of norepinephrine did not further increase mean arterial pressure, which averaged 101 +/- 3 during norepinephrine and 98 +/- 2 mm Hg during insulin plus norepinephrine infusion. Thus, chronic hyperinsulinemia did not increase mean arterial pressure or plasma catecholamines and did not potentiate the blood pressure actions of norepinephrine. These observations provide no evidence that chronic hyperinsulinemia or interactions between insulin and plasma catecholamines cause hypertension in normal dogs. PMID- 2185154 TI - A comparative study of cefamandole and ceftriaxone as prophylaxis in cardiac surgery. AB - We compared the prophylactic use of cefamandole and ceftriaxone in 40 patients undergoing elective cardiac surgery. Postoperative wound infection occurred in one and two patients, respectively, in each group (n.s.), and bronchial superinfection in one patient in each group. In 12 additional patients drug concentrations in plasma and pericardial fluid were measured at different times following the administration of ceftriaxone. Plasma and pericardial fluid concentrations of ceftriaxone were above the minimal inhibitory concentration of susceptible microorganisms for up to 24 h after intravenous administration. We conclude, firstly, that the incidence of infection after cardiac surgery is low with both cefamandole and ceftriaxone prophylaxis. Secondly, efficient plasma and pericardial fluid levels of ceftriaxone last for up to 24 h after intravenous administration. PMID- 2185155 TI - Single dose and conventional treatment for acute bacterial and non-bacterial dysuria and frequency in general practice. AB - A five day course of clavulanate-potentiated amoxicillin (Augmentin) has been compared with a single oral dose of fosfomycin trometamol in the treatment of patients complaining of symptoms suggesting urinary tract infection. The study took place in a single urban general practice of 15,000 patients in Cheshire. The microbiology was performed at a London Teaching Hospital. 141 patients entered the trial. 65 had a significant bacteriuria, 62 of which were assessable for the ability of the trial drugs to eradicate bacteriuria: 29 patients received clavulanate-potentiated amoxicillin and 33 fosfomycin trometamol. The cure rates, assessed at five to ten days and at four to six weeks post treatment, were 72% and 65%, respectively for clavulanate-potentiated amoxicillin and 85% and 81%, respectively for fosfomycin trometamol. Side effects, assessed in all 141 patients, occurred in 11.6% receiving clavulanate-potentiated amoxicillin and in 8.3% receiving fosfomycin. Statistically there is no difference between any of these findings and the effect of sample size is discussed. 69 patients were symptomatic but did not have a significant bacteriuria ("urethral syndrome"). These patients were assessed for the effect of treatment in relieving symptoms: 33 received fosfomycin trometamol and 36 clavulanate-potentiated amoxicillin. The success and speed of relieving the symptoms were very similar in the two groups. The finding that both groups responded equally well appears to refute an aetiological role for lactobacilli and diphtheroids in the "urethral syndrome", since these organisms are resistant to fosfomycin but sensitive to clavulanate potentiated amoxicillin. PMID- 2185156 TI - Short course single daily ceftriaxone monotherapy for acute bacterial meningitis in children: results of a Swiss multicenter study. Part I: Clinical results. AB - In a prospective Swiss multicenter study, 119 children (aged three weeks to 15.5 years) with acute bacterial meningitis were treated with single daily doses of ceftriaxone (100 mg/kg on days one and two and 60 mg/kg thereafter). All patients were randomly assigned to either short course (four, six, seven days) or full course (eight, 12, 14 days) therapy depending on whether they had contracted meningococcal, Haemophilus influenzae type b or pneumococcal meningitis. Bacteriological cure was obtained in 92 children who fully completed the study and in all the 20 culture-positive of the 27 children secondarily excluded from the study for failure to meet all bacteriological and initial safety criteria for continuation in protocol (secondary exclusions). Complete clinical recovery was noted in 105 of 119 patients (88%) and was as frequent in the short course (91%) as in the full course (89%), and as in the secondary exclusion (81%) group. All patients survived. At follow-up examination three to six months after hospital discharge only seven infants and seven children (11.8%), mostly those with poor presentation on admission (p = 0.0012), showed residual neurological sequelae. Side effects of antibiotic therapy were minor but more frequent, albeit not statistically significant (p = 0.065), in children receiving the full course therapy. The results of this study suggest that short course treatment of acute bacterial meningitis in children with single daily ceftriaxone monotherapy is as efficacious as full course therapy and at least as well tolerated. PMID- 2185157 TI - Short course single daily ceftriaxone monotherapy for acute bacterial meningitis in children: results of a Swiss multicenter study. Part II: Bacteriological results. AB - The in vitro activity of ceftriaxone, ampicillin and chloramphenicol was studied at a reference laboratory against the isolates of the first 33 patients enrolled in a pediatric Swiss Multicenter Meningitis Study. The predictive value of the MIC data of 31 of the strains was further corroborated by two sets of bacterial killing curves in broth supplemented with 2 g/l of albumin. Ceftriaxone had the lowest geometric mean MIC values against all groups of isolates except for ampicillin against Streptococcus agalactiae. The bactericidal activity of ceftriaxone and that of ampicillin, alone and in combination with chloramphenicol, was compared at six times the respective MICs and at pharmacologically readily achievable concentrations in cerebrospinal fluid. The bactericidal power of ceftriaxone at six times the MIC was as good or better than that of ampicillin alone or in combination against Neisseria meningitidis and Streptococcus pneumoniae despite the very low drug concentrations of ceftriaxone compared to that of the competitors; and it was barely lower at six times the MIC and at 1 mg/l (a level that is readily surpassed in CSF at the 24 h trough level after a single daily dose of ceftriaxone of 100 mg/kg (neonates 50 mg/kg) than that of ampicillin and chloramphenicol at much higher concentrations against Haemophilus influenzae type b. PMID- 2185159 TI - Changes over time in the clientele and restoration pattern in a dental school prosthodontic department. AB - The clientele and the production of single artificial crowns and fixed partial dentures in the Department of Prosthodontics were compared from 1964/68-1982/87. In the first period 65 per cent of the single crowns were made for women versus 55 per cent in the second. In the first period 69 per cent of the crowns were placed in the upper jaw as against 60 per cent in the second period. On average 1.6 crowns were made per female patient in the first period versus 1.4 per male patient. In the second period both sexes averaged 1.8 units. In both jaws the percentage of root-filled crowned teeth had increased in the second period to 60 per cent from 48 per cent in the upper jaw and 46 per cent in the lower jaw. In both sexes maxillary and mandibular teeth were crowned on average 13 years later in the second period than in the first. Sixty per cent of the fixed partial dentures were made for women in the first period versus 55 per cent in the second. In the first period 74 per cent of the bridges were made for the upper jaw as against 70 per cent in the second period. The mean pontic to abutment ratio was 0.7 in both periods. The maximum number of bridges in the first period were made for patients 40-59 years of age versus 50-69 years in the second period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185158 TI - A randomized trial of ceftriaxone versus oral penicillin for the treatment of early European Lyme borreliosis. AB - In a prospective randomized multicenter trial for the therapy of erythema migrans, 40 patients received ceftriaxone 1 g daily for 5 days and 33 patients obtained phenoxymethylpenicillin, 1 million units 3 times daily, for 12 days. Follow-up was for a mean of 10 +/- 5 months. Eight oral penicillin recipients (24%) and six ceftriaxone recipients (15%) developed minor consecutive manifestations. Two ceftriaxone and one penicillin recipient(s) still had elevated IgG antibody titers 10 to 20 months after therapy. Borrelia burgdorferi could be isolated from the erythema migrans in 29 out of 56 patients (52%) before therapy and in one oral penicillin recipient but none of 24 other patients after therapy. Ceftriaxone was superior to oral penicillin in a subgroup of patients with more than one symptom prior to therapy (p less than 0.01), but not in the overall evaluation of clinical, serological and bacteriological outcome data. Ceftriaxone ought to be preferred to oral penicillin in patients with more severe early Lyme borreliosis. PMID- 2185160 TI - Dentine bonding. Federation Dentaire Internationale Technical Report No. 35. PMID- 2185161 TI - Terminal dentition in elderly patients and implant therapy alternatives. AB - The advent, in recent years, of a tried, tested and reliable implant technique such as the Branemark system, has revolutionized the treatment options open to the prosthodontist. For the edentulous elderly patient the prospects for enhanced quality of life due to the restoration of oral function, comfort and appearance have never been better. For the prosthodontist the new implant systems provide the opportunity to utilize both fixed and removable appliances in combinations and with the use of overdenture designs, with predictable success. PMID- 2185163 TI - Analysis of individual variability among older adults on the Stroop Color Word Interference Test. AB - The present study examines systematic variation in the pattern of response to the Stroop test among a sample of older adults (N = 41), as well as the extent to which various configural patterns of response are related to other individual difference factors. Pattern analysis identified four reasonably prototypic patterns of performance. Three significant discriminant functions, capable of differentiating the four response patterns, were significantly and uniquely related to age, level of cautiousness, and verbal intelligence, respectively. The analyses suggest that performance on the Stroop test is multidimensional with significant variation among older adults, and that different components of performance are differentially related to unique individual difference variables. The findings reinforce the importance of recognizing and understanding the nature of individual variation among elderly individuals in aging research. PMID- 2185162 TI - Reminiscence, life review, and ego integrity in nursing home residents. AB - The purpose of this study was to explore the relationship between dimensions of reminiscence and ego integrity in elderly nursing-home residents. Although frequency of reminiscence was not significantly correlated with ego integrity, using reminiscence for the purpose of life review was positively correlated with high ego-integrity scores in this sample of elderly individuals. This significant, positive relationship supports Butler's life-review theory and provides a link between the life review type of reminiscence and the resolution of Erikson's eighth and final developmental stage--a yardstick of successful aging. PMID- 2185164 TI - Corporatization of medicine: the use of medical management information systems to increase the clinical productivity of physicians. AB - Large corporate health care firms are seeking to reorganize the production of health services under growing cost-containment pressures from government and business payors. Medical management information systems (MMIS) applications are producing an increasing number of financially motivated utilization management interventions designed to constrain wide variations in the practice of medicine. In this article we examine how innovations in MMIS will be used to monitor practitioners' clinical decisions in order to improve the productivity of physicians and other health care personnel. As MMIS technology shifts power from previously autonomous physicians to corporate health care managers, the medical profession is likely to be subjected to far more administrative and bureaucratic controls than conceivable even a few years ago. PMID- 2185165 TI - Increased density of histiocytes in uterine leiomyomas. AB - The histiocyte content of leiomyomata and adjacent, histologically normal myometrium has been quantified morphometrically with the help of recently developed immunostaining for tissue macrophages. Histiocytes identified by immunoreaction for Factor XII subunit A and by double immunofluorescent labelings were found to be identical with tissue macrophages present in normal uteri. Histiocyte counts were significantly higher in leiomyomatous areas than in adjacent normal myometrium, and the distribution of these cells was also changed. In the normal uterine wall, histiocytes could be detected only in the connective tissue septa separating smooth muscle bundles, while in the myomatous nodules they were diffusely scattered throughout the whole area. In addition to providing new information on the cellular composition of leiomyomas, the present observations also raise several questions concerning the possible pathogenetic role of FXIII-positive histiocytes in neoplastic proliferation of uterine smooth muscle. PMID- 2185166 TI - Non-invasive ovarian carcinoma. AB - The subset of ovarian epithelial tumors that is morphologically carcinoma, but has not yet shown any stromal invasion, is discussed. It is emphasized that metastasis is a function of invasive tumors, and that the spread of a noninvasive lesion cannot be explained by the usual concepts of metastasis. The multicentricity of peritoneal origin of ovarian epithelial tumors is a far more likely reason for morbidity and mortality, and is inescapable when the ovaries contain no lesion, when they contain a lesion that is noninvasive, or when the ovaries have been surgically removed. PMID- 2185167 TI - Neoplasms arising in ectopic ovaries: a case of Brenner tumor in an accessory ovary. AB - Accessory and supernumerary ovaries are uncommon congenital anomalies of the female reproductive tract. Tumors arising in ectopic ovaries are extremely rare. We present a case of a Brenner tumor that arose in an accessory ovary and discuss this case in relation to the literature concerning neoplasms in ectopic ovaries. PMID- 2185169 TI - In vitro responses of human peripheral blood mononuclear cells to Plasmodium falciparum antigen. AB - Immunity to malaria involves cell-mediated and humoral responses. The cell mediated reaction is thought to focus particularly on the activity of cells of the macrophage lineage. The ability of antigen-stimulated human peripheral blood lymphocytes to undergo proliferation and produce factors capable of causing macrophage inhibition of parasite growth has been examined. While lymphocyte proliferation, gamma-interferon production, and anti-malarial antibody levels of malaria-exposed Papua New Guinea donors were correlated, and significantly different from Australian subjects, macrophage parasite inhibition was no different in these two groups. Further, there was no evidence for acquired, persistent, cell-mediated immunity, as judged by the monocyte procoagulant test. The results are discussed within the context of human acquired resistance to malaria. PMID- 2185168 TI - Sheep plasma protease inhibitors influencing protease activity and growth of Lucilia cuprina larvae in vitro. AB - The enzyme inhibitors alpha 2-macroglobulin (alpha 2M), anti-thrombin III (AT III) and alpha 1-proteinase inhibitor (alpha 1PI) were isolated from sheep plasma and tested for their ability to affect L. cuprina larval proteases and larval growth in vitro. Casein radial diffusion gels indicated that both alpha 2M and alpha 1PI completely inhibited the protease activity of a larval excretory secretory preparation, while AT III had a partial effect. Casein zymograms revealed that alpha 2M inhibited all of the larval proteases, while AT III was able to modify the normal plaque pattern; alpha 1PI inhibited all plaques except a doublet present at pI 8.5. Larval growth in vitro was significantly inhibited by alpha 2M and AT III (P less than 0.05) when compared to albumin controls but was not affected by alpha 1PI. The levels of alpha 2M in sheep serum were monitored over the course of a larval fly infection. A significant increase in alpha 2M (P less than 0.05) was recorded in the serum of flystruck sheep. It is suggested that, under certain circumstances, these inhibitors may be involved in influencing flystrike through reducing the activity of larval proteases necessary for wound formation and larval nutrition. PMID- 2185170 TI - Studies on the presence and release of proteolytic enzymes (proteinases) in gastro-intestinal nematodes of ruminants. AB - The proteolytic activity of worm homogenates prepared from the third stage larval (L3) and adult stages of the ovine gastro-intestinal nematodes, Nematodirus battus, Ostertagia circumcincta, Trichostrongylus colubriformis, Trichostrongylus vitrinus and Haemonchus contortus, and the rodent intestinal nematode, Nippostrongylus brasiliensis, has been examined using the protein substrates azocasein, azocoll and elastin-orcein. Activity detected in third stage larvae was usually higher than that observed in the adult. Species and stage differences were demonstrated. The in vitro release of proteolytic activity, detected using protein substrates and specific low molecular weight peptide substrates, was, similarly, shown to exhibit a degree of species and stage specificity. Acetylcholinesterase and lactate dehydrogenase activities were determined as reference 'secretory' and 'non-secretory' enzymes, respectively. Three separate peaks of 'tryptic' activity were detected following anion-exchange chromatography of culture fluids derived from adult Ostertagia circumcincta. These peaks could be ascribed to different proteinase classes on the basis of inhibitor sensitivity. PMID- 2185171 TI - Is the laser Doppler flow signal a measure of microcirculatory cell flux? AB - To assess oxygen transport as a function of hematocrit, microcirculatory red blood cell flux (microflux) was measured by laser Doppler flowmetry (LDF) in the isolated rat mesentery as well as in cat sartorius muscle. The hematocrit value was varied from 0.5 to 50% while the perfusion pressure ranged from about 2.7 to 13 kPa. Simultaneously macroflux which is the volume flow times the systemic hematocrit value was determined. The curves LDF versus pressure showed saturation at several hematocrit values conveying the impression of autoregulation of microflux. The macroflux curves, on the other hand, curved upward. To clarify whether this discrepancy had a physiological cause, pressure-microflux as well as pressure-macroflux curves were collected in a flow chamber model where regulatory effects are absent. In the model the same discrepancies between micro- and macroflux as in vivo were observed. These discrepancies are explained by maximum values in velocity of about 3 mm/s and in hematocrit value of less than or equal to 20% which the LDF can discern. The limit in velocity is explained by the low pass filter of 12 kHz of the LDF instrument, the limit in hematocrit measurement is probably caused by the light scattering properties of red blood cell suspensions. A complicated combination of effects appears to be responsible for the linearity of the LDF signal versus macroflux at normal hematocrit value. PMID- 2185172 TI - Medical management of acute postoperative intraocular pressure rises associated with anterior segment ophthalmic laser surgery. PMID- 2185173 TI - Laser cyclophotocoagulation. PMID- 2185174 TI - Optical aids and their application. PMID- 2185175 TI - Considerations and methods for laser surgery in the anterior and posterior segments. PMID- 2185176 TI - Semiconductor diode lasers: a new laser light source in ophthalmology. PMID- 2185177 TI - Principles of photocoagulation using binocular indirect ophthalmoscope laser delivery systems. PMID- 2185178 TI - Ultrasound assessment of renal cortical brightness in infants: is naked eye evaluation reliable? AB - Twenty observers estimated renal cortical brightness compared with the liver in 28 ultrasound images. Their judgment was compared with objective densitometer readings. High inter- and intra-observer variation was found. Estimates of brightness of ultrasound images by eye alone should be interpreted with care. PMID- 2185179 TI - Hepatic ablation using radiofrequency electrocautery. PMID- 2185181 TI - The founding and the early years of Investigative Radiology. PMID- 2185180 TI - Direction of MR imaging. PMID- 2185182 TI - Academic radiology in the United States. 1955-1990. PMID- 2185183 TI - A3CR2. The third sponsor of Investigative Radiology. PMID- 2185184 TI - Federal regulation and reimbursement initiatives affecting academic radiology departments. PMID- 2185185 TI - Twenty-five years of the best of Investigative Radiology. PMID- 2185187 TI - Renal hemodynamic effects of contrast media 1968. PMID- 2185186 TI - In vivo magnification angiography: 1967. PMID- 2185188 TI - Radiologic and histologic investigation of pulmonary oxygen toxicity in newborn guinea pigs 1969. PMID- 2185189 TI - Adverse reactions to contrast agents. Scope of problem 1970. PMID- 2185190 TI - Peripheral bronchographic morphology in the normal human lung 1971. PMID- 2185191 TI - Transthoracic needle biopsy of small peripheral malignant lung lesions 1973. PMID- 2185192 TI - Lymphographic accuracy in Hodgkin's disease and malignant lymphoma with a note on the "reactive" lymph node as a cause of most false-positive lymphograms 1974. PMID- 2185193 TI - Effect of ionic and non-ionic contrast medium on aortic and pulmonary arterial pressure. An angiocardiographic study in rabbits 1975. PMID- 2185194 TI - The mechanism of ischemia in anteroposterior compression of the spinal cord 1975. PMID- 2185195 TI - 1977 Memorial Award Paper. Renal renin and hemodynamic responses to selective renal artery catheterization and angiography. PMID- 2185196 TI - The effect of verification on the assessment of imaging techniques 1983. PMID- 2185197 TI - Difference in the expression pattern of dystrophin on the surface membrane between the skeletal and cardiac muscles of mdx carrier mice. AB - We examined the expression of dystrophin by immunohistochemical and immunoblot analyses in the skeletal and cardiac muscles of Xmdx/X+ heterozygous mice, which were obtained by mating male mdx mice (Xmdx/Y) with female wild type mice (X+/X+). Dystrophin was expressed on the surface membrane in both muscles, but the mode of expression was different between the two muscles. In cardiac muscle, dystrophin positive and negative cells were present in roughly equal numbers intermingled in a mosaic pattern; this was considered to reflect the random inactivation of X-chromosomes in early development. In skeletal muscle, most of the surface membrane was dystrophin positive. There were little signs of fiber necrosis or regeneration, and serum creatine kinase levels were normal. We are at present of opinion that the predominance of dystrophin-positive area in skeletal muscle is due to intracellular diffusion of dystrophin. PMID- 2185198 TI - Use of an alpha-D-glucosidase for the specific cytochemical identification of lateral alpha-D-xylosyl end groups in plant xyloglucans. AB - alpha-Linked D-xylosyl side chains represent the typical feature common to all xyloglucans not shared by other cell wall polysaccharides. Since no easily available alpha-D-xyloxidase is known, advantage was taken of the conformational and configurational homologies between alpha-D-xylopyranose and alpha-D glucopyranose to make an alpha-D-glucosidase-gold complex which was able to recognize alpha-D-xylosyl terminal residues of xyloglucans. This marker was used together with alpha-L-fucosidase gold complex for the double labeling on two different structural features of the same macromolecule in plant primary cell wall. PMID- 2185199 TI - Boar sperm membranes antigens. I. Topography of a mobile glycoprotein of the sperm cell membrane. AB - A monoclonal antibody, designated mAb P86/5, was generated by immunization of female Balb/c mice with a membrane vesicle fraction composed of the outer acrosomal membrane and plasma membrane (PM-OAM). As determined by fluorescence microscopy and electron microscopy P86/5 recognizes a sperm plasma membrane antigen that is restricted to the sperm head. In intact spermatozoa the P86/5 antigen is distributed over the surface of the sperm head with the exception of the rostral region. By comparing the antibody binding pattern generated at 4 degrees C and 25 degrees C, it could be shown that the P86/5-antigen is capable to diffuse freely within the cell membrane overlying the acrosome whereas its lateral mobility is restricted to the post-acrosomal region. The P86/5-antigen had a molecular weight of about 78 kDa as revealed by SDS-PAGE and western blotting. The glycoprotein nature of the P86/5-antigen was established by lectin affinity chromatography. PMID- 2185200 TI - Differential localization of von Willebrand factor, fibronectin and 13-HODE in human endothelial cell cultures. AB - Von Willebrand factor (vWF), fibronectin (FN) and 13-hydroxy-octadecadienoic acid (13-HODE) are known to influence the regulation of the adhesive properties of vascular surfaces. In the present study vWF, FN and 13-HODE were comparatively localized in endothelial cells (EC) and in the extracellular matrix (ECM) produced by EC. An indirect immunofluorescent technique was applied to coverslips containing human EC cultures previously fixed and permeabilized following different procedures: A. Alcohol/acetone; B. Paraformaldehyde alone and C. Paraformaldehyde followed by Triton X-100. vWF was observed inside EC (A), on the ECM produced by EC (B) or in EC and ECM (C) depending on the fixation procedures used. FN was mainly localized in the ECM despite the fixation procedures employed. FN was only seen in relation to cell bodies after strong permeabilization (A). Under our experimental conditions 13-HODE was never found in ECM. This latter antigen was observed randomly dispersed in those preparations fixed with alcohol/acetone, indicating that it is probably extracted by this fixative. 13-HODE was detected in granular shaped structures in EC after permeabilization with detergent (C). These results suggest that the cellular localization of vWF and FN is compatible with an adhesive role related to the abluminal side of ECs. 13-HODE was readily observed after mild permeabilization. This finding would be morphologically consistent with its contribution to the regulation of the vessel wall thromboresistance. PMID- 2185202 TI - Is schizophrenia genetically transmitted? AB - Clinicians and researchers alike have questioned and studied the origin of schizophrenia for decades. Since the early 1900s, a genetic hypothesis has been suggested. This article reviews studies on a possible genetic cause of schizophrenia by use of various methods of comparison: twins, adoption, family history, family studies, and studies of biologic markers. Most researchers conclude that schizophrenia is likely caused by a genetic predisposition coupled with environmental influences. PMID- 2185201 TI - Neuronal pathways in the guinea-pig lumbar sympathetic ganglia as revealed by immunohistochemistry. AB - Tyrosine hydroxylase (TH)- and peptide-immunoreactivity of postganglionic neurons and of nerve fibres in guinea pig lumbar paravertebral sympathetic ganglia 2-4 after transection of the communicating rami and the visceral branches, respectively, were investigated by single- and double-labelling techniques. Six subpopulations of postganglionic neurons were discriminated immunohistochemically: two cell types, which were immunoreactive to only one of the applied antisera - TH, and vasoactive intestinal polypeptide (VIP); and four cell types in which immunoreactivity was colocalized - TH/neuropeptide Y (NPY), NPY/VIP, dynorphin/alpha-neoendorphin and dynorphin (alpha-neoendorphin)/NPY. Small intensely fluorescent (SIF) cells dependent on their location exhibited differential immunobehaviour to NPY-/dynorphin-(alpha-neoendorphin-) and TH antisera. Immunoreactivity to substance P (SP), calcitonin gene-related peptide (CGRP), met-enkephalin-arg-phe (MEAP) and leu-enkephalin was present in nerve fibres but not in postganglionic neurons with frequent colocalization of SP/CGRP- and MEAP/leu-enkephalin- and, sometimes leu-enkephalin/SP- and dynorphin/SP immunoreactivity. TH-immunoreactive intraganglionic nerve fibres were numerically more increased after cutting the visceral branches, than after transection of the communicating rami. Vice versa, NPY-, VIP-, dynorphin- and alpha-neoendorphin immunoreactive nerve fibres were particularly increased in number after cutting the communicating rami. Many but not all of the nerve fibres exhibited colocalization of two of these peptides. SP-, CGRP-, and enkephalin immunoreactive nerve fibres were not visibly affected by cutting the visceral branches but virtually disappeared after lesioning the communicating rami. PMID- 2185203 TI - Salmonella control program introduced. PMID- 2185204 TI - Polycystic kidney disease in a family of Persian cats. AB - A 6-year-old Persian cat was determined to have polycystic kidney disease (PKD). Because of 3 previous clinical reports of PKD in Persian cats, the offspring were examined by use of ultrasonography, which provided evidence of PKD in 3 of the 4 offspring. Because of the genetic transmission of this disease, breeders should be advised not to breed PKD-positive Persian cats. PMID- 2185205 TI - Drug therapy in cats: mechanisms and avoidance of adverse drug reactions. AB - This is the first of a 4-part series concerning drug therapy in cats. In this article, factors that may increase the incidence of type-A adverse drug reactions in cats are discussed. Factors related to species and age differences, drug interactions, and the effects of disease are emphasized. Those that tend to be unique to cats, such as species-induced differences in drug disposition, are described in detail when sufficient information was available from the literature. General recommendations regarding drug administration are made, which will facilitate the implementation of rational drug therapy in cats, thus reducing the incidence of adverse reactions. PMID- 2185206 TI - Estradiol feedback inhibition of luteinizing hormone concentrations in the anestrous sow. AB - The suppressive effects of exogenous 17 beta-estradiol (E2) on LH concentrations in sows that remained anestrus following weaning and in those that returned to estrus were evaluated. Four anestrous and four cyclic sows were treated subcutaneously with silastic implants containing E2 at 13 d after ovariectomy (d 0). Three anestrous and six cyclic sows received silastic implants without E2. Blood was collected at 6-h intervals from d -1 to d 12 and at 15-min intervals for 8 h on d -1, 2, 7 and 12. Sows were treated with 1 microgram GnRH/kg BW at the completion of each 8-h frequent sampling period. Blood was collected at intervals of 10 to 30 min for 3 h after GnRH treatment. Concentrations of E2 remained less than 5 pg/ml in sham-treated sows and were between 20 and 25 pg/ml in E2-treated females. Pulsatile LH concentrations was similar between anestrous and cyclic sows prior to implant treatment. Sham-treated anestrous sows had greater (P less than .05) pulse frequency and mean LH concentrations than E2 treated anestrous sows on d 2, 7 and 12. Differences in pulsatile LH concentrations between E2-treated and sham-treated cyclic sows were not detected. Pulse frequency was less (P less than .05) in E2-treated anestrous sows than in E2-treated cyclic sows on d 7 and 12. Peak LH concentrations were greater (P less than .05) in E2-treated cyclic sows than in E2-treated anestrous sows at each GnRH challenge. These results suggest that the hypothalamo-hypophyseal axis is more sensitive to the negative feedback effects of E2 in anestrous sows than in cyclic sows. In addition, chronic E2 treatment reduces pituitary responsiveness to GnRH to a greater extent in anestrous than in cyclic sows. Failure to return to estrus in swine may be due, at least in part, to an increased sensitivity of the hypothalamo-hypophyseal axis to the negative feedback effect of estradiol. PMID- 2185207 TI - Influence of dietary energy intake on prepubertal development of Brahman bulls. AB - Twelve Brahman bulls (paired by sire, weight and age) were assigned randomly and limit fed to gain either .10 to .25 (moderate gain; MG) or .75 to 1.0 (high gain: HG) kg.hd-1.d-1 to examine the effect of dietary energy on onset of puberty. Hip height (HH), scrotal circumference (SC) and serum samples (20 min for 6 h) were obtained at four times (AGE): 0, 56 and 112 d on feed and after appearance of first motile spermatozoa (FS) in the ejaculate of HG bull of the pair. At FS both bulls of a pair were slaughtered, reproductive tissues were collected and in vitro GnRH release from the median eminence (ME) was measured. Increases in BW, HH and SC were greater (P less than .05) in HG bulls. Basal ME GnRH secretion was greater (P less than .05) in HG bulls. Serum LH concentrations were unchanged by energy level (P greater than .10) but increased (P less than .01) with increasing AGE. AGE and energy level increased (P less than .01) basal, mean and total serum testosterone (T) and these two factors acted synergistically (P less than .01). Height and amplitude of T pulses were increased by energy level (P less than .003) and AGE (P less than .002). Testicular T (P less than .08) and development (P less than .05) were increased in HG bulls. Growth hormone peak height and amplitude concentrations following feeding increased with AGE (P less than .06) but were not altered (P greater than .10) by energy level. Serum triglycerides (P less than .03) and BUN (P less than .003) increased with increasing AGE (P greater than .01). These data indicate that dietary energy level influences onset of puberty most directly at the testicular level. PMID- 2185208 TI - Luteinizing hormone in nutrient-restricted ovariectomized ewes. AB - This study was designed to evaluate profiles of serum concentrations of LH, pituitary content of LH and GnRH receptors, and hypothalamic content of GnRH in undernourished, ovariectomized ewes. In earlier studies, pulsatile secretion of LH diminished as duration of undernutrition progressed in prepubertal or adult ovariectomized ewes. Ewes having similar body condition scores (CS) of 5 to 9 (1 = extremely thin, 5 = moderate, 9 = obese) were fed maintenance or low-energy diets (100% and 60% of NRC requirements, respectively). Blood samples for analysis of LH were collected at 15-min intervals for 4 h at initiation of the project and immediately prior to slaughter. Serum concentrations of LH did not differ (P greater than .05) among groups at the initial sampling period. At slaughter, ewes with CS less than or equal to 2 (n = 7) had lost 26.8 kg (42% of initial weight). Ewes with CS greater than or equal to 3 (n = 12) had lost an average of 13.7 kg (18% of initial weight). Concentrations of LH in ewes with final CS greater than or equal to 3 was similar (P greater than .05) to that observed during the initial sampling period. However, release of LH was reduced (P less than .01) in ewes with CS less than or equal to 2 compared with ewes with CS greater than or equal to 3 (2.6 vs 9.5 and 3.2 vs 10.5 ng/ml for basal and mean concentrations, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185209 TI - Adipose tissue development in the fetal pig examined using monoclonal antibodies. AB - Two anti-adipocyte monoclonal antibodies (MAbs: AD-1 and AD-2) have been used to study the development of dorsal s.c. adipose tissue in fetuses from 50 to 110 d of gestation. Immunofluorescent staining of cryostat sections with each antibody revealed antigen-positive cells in fetal s.c. mesenchyme prior to lipid deposition. Lipid droplets as well as AD-1 and AD-2 positive cells were detected within the underlying muscle at 50 d. From 70 to 110 d of development, the AD-1 and AD-2 MAbs each detected all adipocytes examined, as well as capillaries associated with fat cell clusters in s.c. tissues. Reactivity toward both antibodies, as well as lipid deposition, also was detectable in the muscle underlying the s.c. mesenchyme from 70 d onward. Each MAb possessed a distinct pattern of reactivity. The AD-2 MAb stained arrector pili muscles and vessels in the s.c. mesenchyme and vessels in the underlying muscles, whereas the AD-1 did not. No reactivity using either MAb was detectable toward any other cell types within s.c. tissues. These results established the presence of cells expressing surface determinants found on mature adipocytes and associated capillaries prior to adipogenesis. A lineage relationship between adipocytes and capillary endothelial cells is suggested. PMID- 2185210 TI - John Marcus Evvard, 1884-1948: a brief biography. PMID- 2185211 TI - Interdomain hybrid Tet proteins confer tetracycline resistance only when they are derived from closely related members of the tet gene family. AB - Inner membrane Tet proteins encoded by tet genes in gram-negative bacteria mediate resistance to tetracycline (Tcr) by directing its export. Total sequences for class A, B, and C tet genes demonstrate that their products have a common ancestor, with Tet(A) and Tet(C) being more closely related (78% identical) than either is to Tet(B) (45% identical). The N- and C-terminal halves of Tet(B) and Tet(C) appear to comprise separate domains, and trans-complementation observed between tetracycline sensitive mutants in either domain of Tet(B) suggests separate but interactive functions for these domains. In this present study, interdomain hybrid genes were constructed to express hybrid tet products whose N- and C-terminal halves were derived from different family members [Tet(A/C), Tet(B/C), and Tet(C/B)]. Tet(A/C) specified a level of Tcr comparable to wild type Tet(C) and 60% that of Tet(A), indicating that domains from these closely related tet products can function in cis. Although neither Tet(B/C) nor Tet(C/B) hybrids conferred significant Tcr, cells producing both of these types of hybrid proteins expressed substantial Tcr, indicating that productive interactions can occur in trans between Tet(B/C) and Tet(C/B). Taken together, these results suggest that highly specific interactions between the N- and C-terminal domains are necessary for Tcr and do not occur in individual hybrids derived from the more distant relatives, Tet(B) and Tet(C). This requirement for specific interactions suggests that N- and C-terminal domains have coevolved in each member of the Tet family. PMID- 2185212 TI - Analysis of regulation of the ilvGMEDA operon by using leader-attenuator-galK gene fusions. AB - Five of the genes for the biosynthesis of isoleucine and valine form the ilvGMEDA operon of Escherichia coli K-12. Expression of the operon responds to changes in the availability of isoleucine, leucine, and valine (ILV). Addition of an excess of all three amino acids results in reduced expression of the operon, whereas limitation for one of the three amino acids causes an increase in expression. The operon is preceded by a leader-attenuator which clearly regulates the increased expression that occurs due to reduced aminoacylation of tRNA. To assess the factors that result in the reduced expression of this operon upon the addition of ILV, a series of plasmids were constructed in which the ilv regulatory region was fused to galK. In response to addition of the amino acids, expression of the galK gene fused to the leader-attenuator decreased five- to sevenfold, instead of the twofold observed for the chromosomal operon. A deletion analysis with these plasmids indicated that the ILV-specific decrease in expression required an intact leader-attenuator but not ilvGp2 or the DNA that precedes this promoter. This conclusion was supported by both S1 nuclease analysis of transcription initiation and determination of galK mRNA levels by RNA-RNA hybridization. PMID- 2185213 TI - Secretion and expression of the Pasteurella haemolytica Leukotoxin. AB - The Pasteurella haemolytica leukotoxin gene cluster (lktCABD) is homologous to the Escherichia coli hemolysin locus (hlyCABD). Since the cloned leukotoxin (LktA) is not secreted from E. coli cells, a heteroplasmid complementation system was developed that permits secretion of the leukotoxin from cells expressing the hemolysin transport proteins HlyB and HlyD. We observed that the secreted leukotoxin protein had weak hemolytic activity when activated by either the HlyC or LktC proteins and that LktC expressed in E. coli could confer weak hemolytic activity upon hemolysin. Thus, it appears that the accessory proteins of the leukotoxin and hemolysin gene clusters are functionally similar, although their expression in E. coli is not equivalent. Northern (RNA) blot analysis of the P. haemolytica leukotoxin gene cluster revealed a major 3.5-kilobase transcript that includes the lktC and lktA genes. The start site for this transcript mapped to a cytosine residue 30 nucleotides upstream from the putative start of lktC; a similar initiation site was observed in E. coli, although adjacent cytosine and adenine residues were also utilized. The 3.5-kilobase transcript terminated near the rho-independent terminator structure between lktA and lktB, but transcription may continue, via antitermination or de novo transcription initiation, into the downstream lktB and lktD genes. We propose that the lack of LktB and LktD function in E. coli is a result, at least in part, of poor lktBD transcription and suggest that a P. haemolytica-specific regulator is required for optimal expression of the leukotoxin genes. PMID- 2185214 TI - Organization and sequence analysis of the 2,4-dichlorophenol hydroxylase and dichlorocatechol oxidative operons of plasmid pJP4. AB - Growth of Alcaligenes eutrophus JMP134 on 2,4-dichlorophenoxyacetate requires a 2,4-dichlorphenol hydroxylase encoded by gene tfdB. Catabolism of either 2,4 dichlorophenoxyacetate or 3-chlorobenzoate involves enzymes encoded by the chlorocatechol oxidative operon consisting of tfdCDEF, which converts 3-chloro- and 3,5-dichlorocatechol to maleylacetate and chloromaleylacetate, respectively. Transposon mutagenesis has localized tfdB and tfdCDEF to EcoRI fragment B of plasmid pJP4 (R. H. Don, A. J. Wieghtman, H.-J. Knackmuss, and K. N. Timmis, J. Bacteriol. 161:85-90, 1985). We present the complete nucleotide sequence of tfdB and tfdCDEF contained within a 7,954-base-pair HindIII-SstI fragment from EcoRI fragment B. Sequence and expression analysis of tfdB in Escherichia coli suggested that 2,4-dichlorophenol hydroxylase consists of a single subunit of 65 kilodaltons. The amino acid sequences of proteins encoded by tfdD and tfdE were found to be 63 and 53% identical to those of functionally similar enzymes encoded by clcB and clcD, respectively, from plasmid pAC27 of Pseudomonas putida. P. putida(pAC27) can utilize 3-chlorocatechol but not dichlorinated catechols. A region of DNA adjacent to clcD in pAC27 was found to be 47% identical in amino acid sequence to tfdF, a gene important in catabolizing dichlorocatechols. The region in pAC27 does not appear to encode a protein, suggesting that the absence of a functional trans-chlorodienelactone isomerase may prevent P. putida(pAC27) from utilizing 3,5-dichlorocatechol. PMID- 2185215 TI - Differential mRNA stability controls relative gene expression within the plasmid encoded arsenical resistance operon. AB - The arsenical resistance (ars) operon of the conjugative plasmid R773 encodes an ATP-driven anion extrusion pump, conferring bacterial resistance to arsenicals. The operon contains a regulatory gene, arsR, and three structural genes, arsA, arsB, and arsC. The hydrophilic ArsA and ArsC proteins are produced in large amounts, but the hydrophobic ArsB protein, an integral membrane polypeptide, is synthesized in limited quantities. Northern (RNA-DNA) hybridizations provide evidence that the inducible operon is regulated at the level of transcription. The genes were transcribed in the presence of an inducer (arsenite) as a single polycistronic mRNA with an approximate size of 4.4 kilobases (kb). This transcript was processed to generate relatively stable mRNA species: one of 2.7 kb, encoding the ArsR and ArsA proteins, and a second of 0.5 kb, encoding the ArsC protein. Segmental differences in stability within the polycistronic transcript are proposed to account for the differential expression of the ars genes. In addition, analysis of the mRNA structure at the 5' end of arsB suggests a potential translational block to the synthesis of this membrane protein. PMID- 2185216 TI - Organization of a cluster of erythromycin genes in Saccharopolyspora erythraea. AB - We used a series of gene disruptions and gene replacements to mutagenically characterize 30 kilobases of DNA in the erythromycin resistance gene (ermE) region of the Saccharopolyspora erythraea chromosome. Five previously undiscovered loci involved in the biosynthesis of erythromycin were found, eryBI, eryBII, eryCI, eryCII, and eryH; and three known loci, eryAI, eryG, and ermE, were further characterized. The new Ery phenotype, EryH, was marked by (i) the accumulation of the intermediate 6-deoxyerythronolide B (DEB), suggesting a defect in the operation of the C-6 hydroxylase system, and (ii) a block in the synthesis or addition reactions for the first sugar group. Analyses of ermE mutants indicated that ermE is the only gene required for resistance to erythromycin, and that it is not required for production of the intermediate erythronolide B (EB) or for conversion of the intermediate 3-alpha-mycarosyl erythronolide B (MEB) to erythromycin. Mutations in the eryB and eryC loci were similar to previously reported chemically induced eryB and eryC mutations blocking synthesis or attachment of the two erythromycin sugar groups. Insertion mutations in eryAI, the macrolactone synthetase, defined the largest (at least 9 kilobase) transcription unit of the cluster. These mutants help to define the physical organization of the erythromycin gene cluster, and the eryH mutants provide a source for the production of the intermediate DEB. PMID- 2185217 TI - Isolation and characterization of Candida albicans morphological mutants derepressed for the formation of filamentous hypha-type structures. AB - Several Candida albicans morphological mutants were obtained by a procedure based on a combined treatment with nitrous acid plus UV irradiation and a double enrichment step to increase the proportion of mutants growing as long filamentous structures. Altered cell morphogenesis in these mutants correlated with an altered colonial phenotype. Two of these mutants, C. albicans NEL102 and NEL103, were selected and characterized. Mutant blastoconidia initiated budding but eventually gave rise to filamentous hypha-type formations. These filaments were long and septate, and they branched very regularly at positions near septa. Calcofluor white (which is known to bind chitin-rich areas) stained septa, branching zones, and filament tips very intensely, as observed under the fluorescence microscope. Wild-type hybrids were obtained by fusing protoplasts of strain NEL102 with B14, another morphological mutant previously described as being permanently pseudomycelial, indicating that genetic determinants responsible for the two altered phenotypes are different. The mutants characterized in this work seemed to sequentially express the morphogenic characteristics of C. albicans, from blastoconidia to hyphae, in the absence of any inducer. Further characterization of these strains could be relevant to gain understanding of the genetic control of dimorphism in this species. PMID- 2185218 TI - Rhizobium meliloti glutamate synthase: cloning and initial characterization of the glt locus. AB - The genetic locus glt, encoding glutamate synthase from Rhizobium meliloti 1021, was selected from a pLAFR1 clone bank by complementation of the R. meliloti 41 Glt- mutant AK330. A fragment of cloned DNA complementing this mutant also served to complement the Escherichia coli glt null mutant PA340. Complementation studies using these mutants suggested that glutamate synthase expression requires two complementation groups present at this locus. Genomic Southern analysis using a probe of the R. meliloti 1021 glt region showed a close resemblance between R. meliloti 1021, 41, and 102f34 at glt, whereas R. meliloti 104A14 showed many differences in restriction fragment length polymorphism patterns at this locus. R. meliloti 102f34, but not the other strains, showed an additional region with sequence similarity to glt. Insertion alleles containing transposable kanamycin resistance elements were constructed and used to derive Glt- mutants of R. meliloti 1021 and 102f34. These mutants were unable to assimilate ammonia and were Nod+ Fix+ on alfalfa seedlings. The mutants also showed poor or no growth on nitrogen sources such as glutamate, aspartate, arginine, and histidine, which are utilized by the wild-type parental strains. Strains that remained auxotrophic but grew nearly as well as the wild type on these nitrogen sources were readily isolated from populations of glt insertion mutants, indicating that degradation of these amino acids is negatively regulated in R. meliloti as a result of disruptions of glt. PMID- 2185219 TI - A new model for the penetration of prey cells by bdellovibrios. AB - Bdellovibrio bacteriovorus 109J and most other bdellovibrios cause prey cells to round following penetration. Bdellovibrio sp. strain W does not cause rounding of the prey. Analysis of enzyme activities during the early stages of bdellovibrio attack indicated that strain W differs from most other bdellovibrios in that there is no glycanase activity produced during penetration. Likewise, heat-killed prey were penetrated normally by strain 109J, but the resulting bdelloplast did not become round and no glycanase was detected, indicating that glycanase is not essential for penetration. Peptidoglycan from prey cells penetrated by strain W was sensitive to lysozyme, but these cells were not susceptible to attack and penetration by strain 109J, indicating that peptidoglycan deacetylation is not the primary exclusion mechanism. We propose a model in which it is the peptidase activity of the bdellovibrios which allows them to breach the peptidoglycan of their prey and in which the glycanase activity exhibited by strain 109J and other bdellovibrios is responsible for the rounding of the bdelloplast. PMID- 2185220 TI - Transcriptional induction of an Agrobacterium regulatory gene at tandem promoters by plant-released phenolic compounds, phosphate starvation, and acidic growth media. AB - Transcription of the virG gene of Agrobacterium tumefaciens was previously shown to be expressed from two tandem promoters and to be responsive to three stimuli: plant-released phenolic compounds, phosphate starvation, and acidic media. In this report, I describe a set of deletions and other alterations of the 5' end of virG that show that the upstream promoter (P1) is necessary for induction by phenolic compounds and by phosphate starvation, whereas the downstream promoter (P2) is induced by acidic media. Upstream of promoter P1 there are three copies of a family of sequences (vir boxes) found near all VirA, VirG-inducible promoters. Site-directed mutagenesis of these sequences showed that vir box I and vir box III but not vir box II are needed for induction of P1 by acetosyringone. Induction of P1 by phosphate starvation requires vir box III (or an overlapping site), whereas vir box I and vir box II are not needed. The relative importance of promoters P1 and P2 in vir gene induction was tested by measuring the expression of a virB::lacZ fusion in strains containing mutations at either promoter P1 or P2. Mutations in either promoter significantly attenuated the expression of virB, indicating that both promoters play important roles in vir gene induction. PMID- 2185221 TI - The Cpx proteins of Escherichia coli K-12: evidence that cpxA, ecfB, ssd, and eup mutations all identify the same gene. AB - An existing cpxA(Ts) mutant was resistant to amikacin at levels that inhibited completely the growth of a cpxA+ and a cpxA deletion strain and failed to grow as efficiently on exogenous proline. These properties are similar to those of mutants altered in a gene mapped to the cpxA locus and variously designated as ecfB, ssd, and eup. The amikacin resistance phenotype of the cpxA mutant was inseparable by recombination from the cpxA mutant phenotype (inability to grow at 41 degrees C without exogenous isoleucine and valine) and was recessive to the cpxA+ allele of a recombinant plasmid. Using methods that ensured independent mutations in the cpxA region of the chromosome, we isolated six new amikacin resistant mutants following nitrosoguanidine mutagenesis. Three-factor crosses mapped the mutations to the cpxA locus. When transferred by P1 transduction to a cpxB11 Hfr strain, each of the mutations conferred the Tra- and Ilv- phenotypes characteristic of earlier cpxA mutants. Two of the new mutations led to a significantly impaired ability to utilize exogenous proline, and four led to partial resistance to colicin A. Two of the new cpxA alleles were recessive to the cpxA+ allele, and four were dominant, albeit to different degrees. On the basis of these data, we argue that cpxA, ecfB, eup, and ssd are all the same gene. We discuss the cellular function of the cpxA gene product in that light. PMID- 2185222 TI - Constitutive expression of the phoP regulon attenuates Salmonella virulence and survival within macrophages. AB - The phoP genetic locus is a two-component regulatory system (phoP-phoQ) that controls the expression of genes essential for Salmonella typhimurium virulence and survival within macrophages. Strains with a phoP constitutive mutation (phenotype PhoPC) showed up to 10-fold greater expression of phoP-activated genes (pag loci) than did strains with a wild-type phoP locus (phenotype PhoP+). While the phoP constitutive mutation resulted in increased expression of pag loci, it also dramatically reduced the expression of other protein species. Comparison of the protein content of PhoP+ and PhoPC strains by two-dimensional protein gel electrophoresis demonstrated that at least 40 separate protein species were changed in expression as a result of this mutation. The PhoPC S. typhimurium were found to be attenuated for virulence and survival within macrophages. This finding suggests that a balanced PhoP-PhoQ regulatory response, which allows expression of phoP-repressed as well as -activated genes, is required for full virulence of S. typhimurium. We have further shown that small numbers of PhoPC bacteria can be used as a live attenuated vaccine to protect against mouse typhoid. As few as 15 PhoPC bacteria protected mice against challenge with 10(5) 50% lethal doses of wild-type organisms, suggesting that important protective antigens are regulated by the PhoP-PhoQ virulence regulon. PMID- 2185223 TI - Cloning of the Zymomonas mobilis structural gene encoding alcohol dehydrogenase I (adhA): sequence comparison and expression in Escherichia coli. AB - Zymomonas mobilis ferments sugars to produce ethanol with two biochemically distinct isoenzymes of alcohol dehydrogenase. The adhA gene encoding alcohol dehydrogenase I has now been sequenced and compared with the adhB gene, which encodes the second isoenzyme. The deduced amino acid sequences for these gene products exhibited no apparent homology. Alcohol dehydrogenase I contained 337 amino acids, with a subunit molecular weight of 36,096. Based on comparisons of primary amino acid sequences, this enzyme belongs to the family of zinc alcohol dehydrogenases which have been described primarily in eucaryotes. Nearly all of the 22 strictly conserved amino acids in this group were also conserved in Z. mobilis alcohol dehydrogenase I. Alcohol dehydrogenase I is an abundant protein, although adhA lacked many of the features previously reported in four other highly expressed genes from Z. mobilis. Codon usage in adhA is not highly biased and includes many codons which were unused by pdc, adhB, gap, and pgk. The ribosomal binding region of adhA lacked the canonical Shine-Dalgarno sequence found in the other highly expressed genes from Z. mobilis. Although these features may facilitate the expression of high enzyme levels, they do not appear to be essential for the expression of Z. mobilis adhA. PMID- 2185224 TI - Purification and characterization of a protease from Clostridium botulinum type A that nicks single-chain type A botulinum neurotoxin into the di-chain form. AB - A protease that nicks the approximately 150-kilodalton (kDa) single-chain type A botulinum neurotoxin into the approximately 150-kDa di-chain form in vitro was isolated from Clostridium botulinum type A (Hall strain) cultures. The di-chain neurotoxin generated in vitro is composed of an approximately 50-kDa light chain and an approximately 100-kDa heavy chain which are disulfide linked and is indistinguishable from the di-chain neurotoxin that forms in vivo and is routinely isolated (M.L. Dekleva and B.R. DasGupta, Biochem. Biophys. Res. Commun. 162:767-772, 1989). This enzyme was purified greater than 1,000-fold by ammonium sulfate precipitation, QAE-Sephadex Q-50, Sephadex G-100, and CM Sephadex C-50 chromatography steps with the synthetic substrate N-benzoyl-DL arginine-p-nitroanilide. The approximately 62-kDa amidase (protease) is a complex of 15.5- and 48-kDa polypeptides (determined by polyacrylamide gel electrophoresis) that could not be separated without sodium dodecyl sulfate. The enzyme has an isoelectric point of pH 5.73, a pH optimum of 6.2 to 6.4, an absolute requirement for a thiol-reducing agent as well as a divalent metallic cation (probably Ca2+) for activity, and a temperature optimum of 70 degrees C. Tests with several synthetic substrates indicated the high specificity of the enzyme for arginyl amide bonds. PMID- 2185225 TI - Site-directed mutations in the repA C-terminal region of plasmid Rts1: pleiotropic effects on the replication and autorepressor functions. AB - We induced site-directed mutations near the 3' terminus of the gene repA, which encodes the protein of 288 amino acid residues essential for plasmid Rts1 replication, and obtained seven repA mutants. Three of them contained small deletions at the 3' terminus. Mutant repAz delta C4, which encodes a RepA protein that lacks the C-terminal four amino acids, expressed a high-copy-number phenotype and had lost both autorepressor and incompatibility functions. Deletion of one additional amino acid residue to form the RepAz delta C5 protein caused restoration of the wild-type copy number and strong incompatibility. Studies of the remaining four repA mutants, each of which contained a single amino acid substitution near the RepA C terminus, suggested that Lys-268 is involved in both ori(Rts1) activation and autorepressor-incompatibility activities and that Arg 279 contributes to ori(Rts1) activation but not to incompatibility. Lys-268 is part of a dual-lysine sequence with Lys-267 and is located 21 amino acids upstream of the RepA C terminus. A dual-lysine sequence is also found at a similar position in both mini-F RepE and mini-P1 RepA proteins. PMID- 2185226 TI - Mutation and cloning of eryG, the structural gene for erythromycin O methyltransferase from Saccharopolyspora erythraea, and expression of eryG in Escherichia coli. AB - A mutant strain derived by chemical mutagenesis of Saccharopolyspora erythraea (formerly known as Streptomyces erythreus) was isolated that accumulated erythromycin C and, to a lesser extent, its precursor, erythromycin D, with little or no production of erythromycin A or erythromycin B (the 3"-O-methylation products of erythromycin C and D, respectively). This mutant lacked detectable erythromycin O-methyltransferase activity with erythromycin C, erythromycin D, or the analogs 2-norerythromycin C and 2-norerythromycin D as substrates. A 4.5 kilobase DNA fragment from S. erythraea originating approximately 5 kilobases from the erythromycin resistance gene ermE was identified that regenerated the parental phenotype and restored erythromycin O-methyltransferase activity when transformed into the erythromycin O-methyltransferase-negative mutant. Erythromycin O-methyltransferase activity was detected when the 4.5-kilobase fragment was fused to the lacZ promoter and introduced into Escherichia coli. The activity was dependent on the orientation of the DNA relative to lacZ. We have designated this genotype eryG in agreement with Weber et al. (J.M. Weber, B. Schoner, and R. Losick, Gene 75:235-241, 1989). It thus appears that a single enzyme catalyzes all of the 3"-O-methylation reactions of the erythromycin biosynthetic pathway in S. erythraea and that eryG codes for the structural gene of this enzyme. PMID- 2185227 TI - Regulation of the glyoxylate bypass operon: cloning and characterization of iclR. AB - In Escherichia coli, expression of the glyoxylate bypass operon appears to be controlled, in part, by the product of iclR+. Mutations in iclR have been found to yield constitutive expression of this operon, suggesting that iclR+ encodes a repressor protein. We have cloned iclR+ by taking advantage of its tight genetic linkage with the glyoxylate bypass operon. The clone complemented a mutant allele of iclR in trans, restoring an inducible phenotype for this operon. Deletion analysis identified a region of ca. 900 base pairs that was necessary and sufficient for complementation. The nucleotide sequence of the insert was then determined. Translation of this sequence revealed an open reading frame capable of encoding a protein with Mr 29,741 preceded by a potential Shine-Dalgarno ribosome-binding site. The deduced amino acid sequence includes a region at the amino terminus that may form a helix-turn-helix motif, a structure found in many DNA-binding domains. PMID- 2185228 TI - Kinetics of iron acquisition from ferric siderophores by Paracoccus denitrificans. AB - The kinetics of iron accumulation by iron-starved Paracoccus denitrificans during the first 2 min of exposure to 55Fe-labeled ferric siderophore chelates is described. Iron is acquired from the ferric chelate of the natural siderophore L parabactin in a process exhibiting biphastic kinetics by Lineweaver-Burk analysis. The kinetic data for 1 microM less than [Fe L-parabactin] less than 10 microM fit a regression line which suggests a low-affinity system (Km = 3.9 +/- 1.2 microM, Vmax = 494 pg-atoms of 55Fe min-1 mg of protein-1), whereas the data for 0.1 microM less than or equal to [Fe L-parabactin] less than or equal to 1 microM fit another line consistent with a high-affinity system (Km = 0.24 +/- 0.06 microM, Vmax = 108 pg-atoms of 55Fe min-1 mg of protein-1). The Km of the high-affinity uptake is comparable to the binding affinity we had previously reported for the purified ferric L-parabactin receptor protein in the outer membrane. In marked contrast, ferric D-parabactin data fit a single regression line corresponding to a simple Michaelis-Menten process with comparatively low affinity (Km = 3.1 +/- 0.9 microM, Vmax = 125 pg-atoms of 55Fe min-1 mg of protein-1). Other catecholamide siderophores with an intact oxazoline ring derived from L-threonine (L-homoparabactin, L-agrobactin, and L-vibriobactin) also exhibit biphasic kinetics with a high-affinity component similar to ferric L parabactin. Circular dichroism confirmed that these ferric chelates, like ferric L-parabactin, exist as the lambda enantiomers. The A forms ferric parabactin (ferrin D- and L-parabactin A), in which the oxazoline ring is hydrolyzed to the open-chain threonyl structure, exhibit linear kinetics with a comparatively high Km (1.4 +/- 0.3 microM) and high Vmax (324 pg-atoms of 55Fe min-1 of protein-1). Furthermore, the marked stereospecificity seen between ferric D- and L parabactins is absent; i.e., iron acquisition from ferric parabactin A is non stereospecific. The mechanistic implications of these findings in relation to a stereospecific high-affinity binding followed by a nonstereospecific postreceptor processing is discussed. PMID- 2185229 TI - Constitutive synthesis of a transport function encoded by the Thiobacillus ferrooxidans merC gene cloned in Escherichia coli. AB - Mercuric reductase activity determined by the Thiobacillus ferrooxidans merA gene (cloned and expressed constitutively in Escherichia coli) was measured by volatilization of 203Hg2+. (The absence of a merR regulatory gene in the cloned Thiobacillus mer determinant provides a basis for the constitutive synthesis of this system.) In the absence of the Thiobacillus merC transport gene, the mercury volatilization activity was cryptic and was not seen with whole cells but only with sonication-disrupted cells. The Thiobacillus merC transport function was compared with transport via the merT-merP system of plasmid pDU1358. Both systems, cloned and expressed in E. coli, governed enhanced uptake of 203Hg2+ in a temperature- and concentration-dependent fashion. Uptake via MerT-MerP was greater and conferred greater hypersensitivity to Hg2+ than did uptake with MerC. Mercury uptake was inhibited by N-ethylmaleimide but not by EDTA. Ag+ salts inhibited mercury uptake by the MerT-MerP system but did not inhibit uptake via MerC. Radioactive mercury accumulated by the MerT-MerP and by the MerC systems was exchangeable with nonradioactive Hg2+. PMID- 2185230 TI - Molecular cloning of the protocatechuate 4,5-dioxygenase genes of Pseudomonas paucimobilis. AB - We determined the nucleotide sequence of a 1.9-kilobase fragment of Pseudomonas paucimobilis SYK6 chromosomal DNA that included genes encoding protocatechuate 4,5-dioxygenase, the enzyme responsible for the aromatic ring fission of protocatechuate. Two open reading frames of 417 and 906 base pairs were found that had no homology with previously reported sequences, including those encoding protocatechuate 3,4-dioxygenase. Since both open reading frames were indispensable for the enzyme activity, they should encode the subunits of protocatechuate 4,5-dioxygenase. We named these genes ligA and ligB. Protocatechuate 4,5-dioxygenase was efficiently expressed in Escherichia coli with the aid of the lac promoter, and the polypeptides of the ligA and ligB gene products were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and amino acid sequencing. PMID- 2185231 TI - Inhibition of transcription of cytosine-containing DNA in vitro by the alc gene product of bacteriophage T4. AB - The alc gene product (gpalc) of bacteriophage T4 inhibits the transcription of cytosine-containing DNA in vivo. We examined its effect on transcription in vitro by comparing RNA polymerase isolated from Escherichia coli infected with either wild-type T4D+ or alc mutants. A 50 to 60% decline in RNA polymerase activity, measured on phage T7 DNA, was observed by 1 min after infection with either T4D+ or alc mutants; this did not occur when the infecting phage lacked gpalt. In the case of the T4D+ strain but not alc mutants, this was followed by a further decrease. By 5 min after infection the activity of alc mutants was 1.5 to 2.5 times greater than that of the wild type on various cytosine-containing DNA templates, whereas there was little or no difference in activity on T4 HMdC-DNA, in agreement with the in vivo specificity. Effects on transcript initiation and elongation were distinguished by using a T7 phage DNA template. Rifampin challenge, end-labeling with [gamma-32P]ATP, and selective initiation with a dinucleotide all indicate that the decreased in vitro activity of the wild-type polymerase relative to that of the alc mutants was due to inhibition of elongation, not to any difference in initiation rates. Wild-type (but not mutated) gpalc copurified with RNA polymerase on heparin agarose but not in subsequent steps. Immunoprecipitation of modified RNA polymerase also indicated that gpalc was not tightly bound to RNA polymerase intracellularly. It thus appears likely that gpalc inhibits transcript elongation on cytosine-containing DNA by interacting with actively transcribing core polymerase as a complex with the enzyme and cytosine-rich stretches of the template. PMID- 2185232 TI - Second-site revertants of the P1 copN22 copy mutant. AB - Miniplasmids with the P1 copN22 mutation have a copy number about seven times that of the wild type. Selection for reduced copy number from this plasmid led to the isolation of second-site pseudorevertants, called poc mutants. DNA sequence analysis showed that all six independent poc mutants have a single base change in the same codon of the repA gene. This implicates the amino acid at this location, either directly or indirectly, in interactions important for copy number control. PMID- 2185233 TI - Starvation-induced cross protection against osmotic challenge in Escherichia coli. AB - Stationary-phase Escherichia coli cultures showed enhanced osmotic resistance as compared with cultures in mid-logarithmic growth or preadapted to osmotic stress. The osmotolerance that developed during starvation or osmotic adaptation required de novo protein synthesis. Of the 22 polypeptides induced during osmotic shock, five were also starvation proteins. PMID- 2185234 TI - Characterization of the defect in the Escherichia coli mutT1 mutator gene. AB - With a probe constructed from the wild-type gene, a DNA fragment containing the entire mutT1 mutator gene was isolated and cloned into pUC18. Nucleotide sequence analysis revealed that the mutator defect was most likely due to an IS1 insertion into the wild-type gene. PMID- 2185235 TI - The DNA adenine methyltransferase (dam+) gene of bacteriophage T4 reverses the mutator phenotype of an Escherichia coli dam mutant. AB - The mutator phenotype of Escherichia coli dam mutants was found to be reversed by introduction of the bacteriophage T4 gene for DNA adenine methyltransferase. This precludes a direct role for the E. coli DNA adenine methyltransferase in mismatch repair, in addition to its role in strand discrimination, as suggested by earlier studies (S. L. Schlagman, S. Hattman, and M. G. Marinus, J. Bacteriol. 165:896 900, 1986). PMID- 2185236 TI - Nucleotide sequence and characteristics of the gene for L-lactate dehydrogenase of Thermus aquaticus YT-1 and the deduced amino acid sequence of the enzyme. AB - The gene for L-lactate dehydrogenase (LDH) from Thermus aquaticus YT-1 was cloned in Escherichia coli, using the Thermus caldophilus LDH gene as a hybridization probe, and its complete nucleotide sequence was determined. The LDH gene comprised 930 base pairs, starting with a GTG initiation codon. Its sequence had high homology (85.8% identity) with the LDH gene of T. caldophilus. The G + C content of the T. aquaticus gene was 70.9%, higher than that of the chromosomal DNA (67.4%). In particular, that in the third position of the codons used was 91.0%, similar to the T. caldophilus gene. The primary structure of T. aquaticus LDH was deduced from the nucleotide sequence of the LDH gene. It comprises 310 amino acid residues, as does T. caldophilus LDH, and its molecular mass was calculated to be 33,210 daltons. The amino acid sequence of the T. aquaticus LDH had 87.1% identity with that of the T. caldophilus LDH. At 23 positions, the respective residues differed in charge and polarity. These differences must be related to the differences in kinetic properties between the two enzymes. The constructed plasmid overproduced the T. aquaticus LDH in E. coli. PMID- 2185237 TI - Site-directed mutagenesis of human prorenin. Substitution of three arginine residues in the propeptide with glutamine residues yields active prorenin. AB - Human prorenin is an inactive zymogen comprising 43 amino acid residues at the amino terminus of human renin. The aim of this work was to determine why prorenin is inactive at neutral pH. Eighteen different mutant prorenins, in which positively charged residues in the propeptide were substituted with either glutamine (Gln) or lysine (Lys) residues by site-directed mutagenesis, were expressed in COS-7 cells and characterized. By replacing each of the three arginine (Arg) residues (Arg10P, Arg15P, and Arg20P) with Gln residues, partially active prorenins were produced, which exhibited significant but not full renin activity without trypsin activation. The effect of double or triple amino acid substitutions on the appearance of active prorenin was cumulative, the activity reaching about 80% in a mutant in which all the three Arg residues were replaced by Gln residues. In contrast, mutant prorenins with Lys residues substituted for the Arg residues were inactive. These results clearly indicate that the positive charges of the three Arg residues are essential for maintenance of the human prorenin in an inactive form. PMID- 2185238 TI - Complete primary structure of the human estrogen-responsive gene (pS2) product. AB - pS2 is a human gene whose transcription is directly triggered by estrogen in human breast cancer cells (MCF-7). We described here the complete primary structure of the pS2 gene product. The pS2 protein purified from conditioned medium of MCF-7 cells was S-pyridylethylated and digested with TPCK-trypsin. Five major fragments were obtained by reverse-phase HPLC. Amino acid sequence analysis of these tryptic peptides established that the pS2 protein comprises a 60-amino acid polypeptide. The sequence of the pS2 protein was completely identical to that deduced from the nucleotide sequence of the pS2 gene, if the signal polypeptide is excluded. Furthermore, two cDNA clones encoding an 84-amino acid precursor pS2 protein were isolated from a cDNA library which was constructed with RNA from MCF-7 cells cultured in the presence of estrogen. The nucleotide sequence of one clone (pS2B1) was identical to that of pS2 cDNA previously reported except for one nucleotide in the 3' untranslated region. The other clone (pS2B2) was longer by 73 nucleotides, at the 5' end, than pS2B1. The additional 73 nucleotides are located just upstream of the sequence of pS2B1 in the structure of the pS2 gene, indicating that the pS2 gene has two start sites for transcription. However, a mRNA molecule corresponding to pS2B1 but not to pS2B2 was detected in the cells on RNA blot hybridization analysis, indicating that one transcriptional start site is mainly used. PMID- 2185239 TI - Monoclonal antibody studies on the properties and regulation of murine ornithine decarboxylase antizymes. AB - Seven monoclonal antibodies were prepared against rat liver ornithine decarboxylase antizyme, a unique regulatory protein of the enzyme induced by its products. The monoclonal antibodies reacted with antizymes from all the rat and mouse tissues examined, indicating that these antizymes share similar structural features, though some size heterogeneity has been reported for rat antizymes. A sandwich enzyme immunoassay which could detect 0.1 ng of antizyme was developed using these antibodies. The amount of antizyme protein in rat liver, analyzed by the immunoassay, increased on putrescine treatment in parallel with antizyme activity, indicating that the changes in antizyme activity were attributable to the changes in the amount of its protein. The putrescine-induced increase of antizyme protein, as well as that of its activity, was completely inhibited by cycloheximide but not by actinomycin D, confirming the importance of post transcriptional regulation in antizyme induction. PMID- 2185240 TI - Intrinsically bent DNA. PMID- 2185242 TI - The ferrochelatase from Saccharomyces cerevisiae. Sequence, disruption, and expression of its structural gene HEM15. AB - The HEM15 gene in Saccharomyces cerevisiae encodes ferrochelatase (EC 4.99.1.1, protoheme ferrolyase), a mitochondrial inner membrane-bound enzyme which catalyzes the insertion of ferrous ion into protoporphyrin IX, the last step in protoheme biosynthesis. The gene was isolated by functional complementation of a hem15 mutant. Sequence analysis of a 2.9-kilobase genomic DNA fragment revealed an open reading frame of 1179 nucleotides, plus a gene coding for a tRNA(Val)(GUU) and delta elements downstream from the 3'-end of HEM15. The open reading frame encodes a precursor form of the protein containing a 31-amino acid presequence. The mature enzyme contains 362 amino acid residues; its calculated molecular weight (40,900) and predicted amino-terminal sequence agree with those determined from the purified protein. It is relatively abundant in lysine (9%) and contains no apparent transmembrane segment. Disruption of the HEM15 gene led to non-viable cells in certain genetic background. Northern (RNA) analysis showed a slight (1.5-2-fold) repression of HEM15 expression by glucose. PMID- 2185241 TI - Streptococcal-host interactions. Structural and functional analysis of a Streptococcus sanguis receptor for a human salivary glycoprotein. AB - Colonization of oral tissues by Streptococcus sanguis may be influenced by a mucin-like salivary glycoprotein (SAG) through a calcium-dependent interaction with a specific bacterial receptor. We report the nucleotide and deduced amino acid sequence of the S. sanguis receptor (SSP-5) and show that this protein may bind sialic acid residues of SAG. The SSP-5 protein contains three unique structural domains, two of which consist of repetitive amino acid sequences. The N-terminal domain is comprised of four tandem copies of an 82-residue repeat which exhibits homology to M protein of Streptococcus pyogenes. This region is highly charged and predicted to be alpha-helical. A second hydrophilic repetitive domain consists of three copies of a 39-amino acid sequence containing 30% proline flanked by nonrepetitive proline-rich sequence. The third domain consists of 48% proline and resides near the C terminus of the protein. Secondary structure analysis of the SSP-5 sequence also identified four potential helix turn-helix motifs that resembled E-F hand calcium binding domains. The SSP-5 protein is highly homologous to a surface antigen expressed by the mutans streptococci and the domain structure of SSP-5 is conserved within this family of proteins. The interactions of SSP-5 and of intact S. sanguis with SAG were inhibited by neuraminidase digestion of the salivary glycoprotein and by simple sugars containing sialic acid, suggesting that sialic acid is the primary ligand involved in the binding reaction. PMID- 2185243 TI - Expression, purification, and characterization of protein kinase C-epsilon. AB - Of the recently described members of the protein kinase C (PKC) family (-delta, epsilon, -zeta), no detailed properties of the purified enzymes have been presented. Here we describe the expression of PKC-epsilon in insect cells using a baculovirus vector. The recombinant enzyme has been purified to homogeneity by sequential chromatography on DEAE-cellulose, serine-Sepharose, Mono Q, and Superose 12; the protein shows a molecular mass of 90 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. PKC-epsilon is dependent upon phospholipid and diacylglycerol (or phorbol esters) for activity and displays a pattern of specificity for these effectors similar to other PKC isotypes. Similarly, inhibition of PKC-epsilon by staurosporine and H-7 parallels inhibition of other PKC isotypes. However, unlike PKC-alpha, -beta, and -gamma, PKC-epsilon shows no dependence upon Ca2+. Furthermore, the substrate specificity of PKC-epsilon is quite different from other characterized PKCs. The importance of functional diversity within the PKC family is discussed. PMID- 2185244 TI - Expression and characterization of a recombinant human parathyroid hormone secreted by Escherichia coli employing the staphylococcal protein A promoter and signal sequence. AB - Human parathyroid hormone (hPTH) is a peptide hormone consisting of 84 amino acids (hPTH(1-84)). Employing the promoter and signal sequence of Staphylococcus aureus-protein A we have expressed hPTH in Escherichia coli. The expressed proteins are excreted to the growth medium, allowing for rapid and easy purification of the desired products. By amino acid sequence analysis and mass spectrometry, we have shown that the major excreted product is correctly processed human identical hPTH(1-84). The purified recombinant hPTH(1-84) stimulates adenylate cyclase activity in rat osteosarcoma cell membranes to exactly the same extent as synthetic parathyroid hormone standards, indicating that the recombinant product has full biological activity. PMID- 2185245 TI - ATP stimulates the hydrolysis of phosphatidylethanolamine in NIH 3T3 cells. Potentiating effects of guanosine triphosphates and sphingosine. AB - Recently, phospholipase D-mediated hydrolysis of phosphatidylethanolamine (PtdEtn) was shown to be stimulated by activators of protein kinase C (Kiss, Z., and Anderson, W. B. (1989) J. Biol. Chem. 264, 1483-1487), suggesting that PtdEtn metabolism may play a role in signal transduction. Here we have studied the possible regulation of PtdEtn hydrolysis by adenine and guanine nucleotides, as well as by sphingosine, both in membranes isolated from [14C]ethanolamine- or [32P]PtdEtn-prelabeled NIH 3T3 cells and in intact cells. In isolated membranes both ATP and ADP stimulated the hydrolysis of PtdEtn. Both nucleotides had maximal (approximately 2-fold) effects at about 0.5 mM concentration. The main water-soluble product of [14C]PtdEtn hydrolysis was [14C]ethanolamine, while in [32P] PtdEtn-prelabeled membranes the nucleotides stimulated the formation of [32P]phosphatidic acid, suggesting the involvement of a phospholipase D-type enzyme. The hydrolysis-resistant analogs of GTP, such as guanosine 5'-3-O (thio)triphosphate and guanyl-5'-yl imidodiphosphate, greatly potentiated the stimulatory effects of ATP and ADP on PtdEtn hydrolysis. On the other hand, the nonphosphorylating analogs of ATP, adenyl-5'-yl beta,gamma-imidodiphosphate and beta,gamma-methyl-eneadenosine 5'-triphosphate, failed to stimulate PtdEtn hydrolysis both in the absence and presence of guanosine triphosphates. Sphingosine, while exhibiting no effect alone, had a relatively modest (1.2-1.3 fold) potentiating effect on ATP-stimulated PtdEtn hydrolysis in isolated membranes. The effect of sphingosine was mimicked by threo- and erythrosphinganines, while N-acetylsphingosine was without effect. In studies with [14C]ethanolamine-prelabeled intact NIH 3T3 cells, externally added ATP did not stimulate PtdEtn hydrolysis. In contrast, sphingosine and sphinganines had much greater stimulatory effects on PtdEtn hydrolysis in intact cells than with isolated membranes. These data indicate that PtdEtn hydrolysis may be regulated by adenine and guanine nucleotides in addition to, or in cooperation with, the activators of protein kinase C, and that sphingosine may be an additional regulator of PtdEtn hydrolysis. PMID- 2185246 TI - Kinetic analysis of the pre-equilibrium steps in the self-assembly of RecA protein from Escherichia coli. AB - Total intensity light scattering is employed to investigate the self-assembly kinetics of RecA protein. Reaction conditions are employed where the kinetics of self-assembly are slow enough to yield reliable scattered intensity measurements over the range of scattering angles from 40 to 130 degrees as a function of time. From these measurements the time-dependent behavior of the weight average molecular weight, Mr, and radius of gyration, RG, of the associating protein species as a function of [MgCl2], [NaCl], [RecA], and pH was determined. The temperature dependence of RecA self-assembly was also investigated and allowed an evaluation of the activation thermodynamic parameters of association. Results reveal RecA self-assembly is bi-phasic under all conditions examined. The first phase, referred to as "filamentation" is second-order in [RecA] and occurs via a quasi linear condensation scheme with an Arrhenius activation energy of 88.6 kcal/mol. Filamentation assembly involves the uptake of one proton, one MgCl2, the release of five to six NaCls, and is driven by the release of approximately 70 water molecules. The evaluated activation parameters of the first kinetic phase are consistent with the proposition that linear self-assembly of RecA protein into ordered filaments is entropically driven. The second kinetic phase, referred to as "bundling" is greater than second-order in both [RecA] and [MgCl2], is considerably slower that filamentation assembly, and is apparently initiated by 2nd order collisions of linear filaments. PMID- 2185247 TI - Discoordinate expression of the yeast mitochondrial ribosomal protein MRP1. AB - We have examined expression of the protein coded within the MRP 1 locus of Saccharomyces cerevisiae. Direct evidence is provided for the assignment of the MRP1 gene product as a protein component of the small subunit of mitochondrial ribosomes. Further studies examined the extent to which the expression of the MRP1 protein is coordinated with the expression of other mitochondrial ribosomal components coded in the nuclear and mitochondrial genomes. Extra copies of the MRP1 gene were introduced into yeast cells to perturb expression from MRP1 relative to other mitochondrial ribosomal components to determine whether forms of regulation function to limit the accumulation of either MRP1 mRNA or protein under these conditions. Increases in MRP1 gene dosage were accompanied by substantial increases in both MRP1 mRNA and protein, indicating that their accumulation was not linked to the level of expression of other mitochondrial ribosomal components. This conclusion was confirmed by additional studies that showed that the accumulation of the MRP1 protein was unaffected in cells that did not express mitochondrially-encoded rRNAs. These results contrast with previous studies on the expression of two other mitochondrial ribosomal proteins indicating that regulatory properties of mitochondrial ribosomal proteins are quite diverse. PMID- 2185248 TI - Cloning and functional analysis of the arginyl-tRNA-protein transferase gene ATE1 of Saccharomyces cerevisiae. AB - Aminoacyl-tRNA-protein transferases (Arg-transferases) catalyze post translational conjugation of specific amino acids to the amino termini of acceptor proteins. A function of these enzymes in eukaryotes has been shown to involve the conjugation of destabilizing amino acids to the amino termini of short-lived proteins, these reactions being a part of the N-end rule pathway of protein degradation (Gonda, D. K., Bachmair, A., Wunning, I., Tobias, J. W., Lane, W. S., and Varshavsky, A. (1989) J. Biol. Chem. 264, 16700-16712). We have cloned the ATE1 gene of the yeast Saccharomyces cerevisiae which encodes arginyl tRNA-protein transferase. ATE1 gives rise to a approximately 1.6-kilobase mRNA and codes for a 503-residue protein. Expression of the yeast ATE1 gene in Escherichia coli, which lacks Arg-transferases, was used to show that the ATE1 protein possesses the Arg-transferase activity. Null ate1 mutants are viable but lack the Arg-transferase activity and are unable to degrade those substrates of the N-end rule pathway that start with residues recognized by the Arg transferase. PMID- 2185249 TI - Purification and properties of the bacteriophage P2 ogr gene product. A prokaryotic zinc-binding transcriptional activator. AB - The bacteriophage P2 ogr gene product, a 72-residue basic protein rich in cysteine and histidine, is a positive regulatory factor for phage late gene transcription in both P2 and satellite phage P4. We have developed a simple purification procedure for Ogr protein synthesized from an overproducing plasmid. Inclusion bodies formed upon overproduction were denatured using 8 M urea, and the overproduced protein was purified by gel filtration. The purified Ogr was allowed to refold under optimized conditions and was subsequently shown to be able to transactivate the phage P4 late promoter Psid in an in vitro coupled transcription-translation system. Using a 65Zn blotting method and absorption spectroscopy, we show that Ogr is a zinc-binding protein and that the conserved cysteine residues are involved in forming a complex with Zn(II). The purification procedure described allows Ogr to be obtained in both high purity and yield. PMID- 2185250 TI - Truncations of a secretory protein define minimum lengths required for binding to signal recognition particle and translocation across the endoplasmic reticulum membrane. AB - Nascent preproinsulin interacts with endoplasmic reticulum membranes after approximately 70-80 residues of the 116-amino acid precursor are polymerized (Eskridge, E. M., and Shields, D. (1983) J. Biol. Chem. 258, 11487-11491). To understand the relationship between the size of a nascent presecretory polypeptide and the efficiency of its translocation across the endoplasmic reticulum membrane, recombinant DNA molecules were generated that encoded a series of preproinsulin derivatives with the same NH2 terminus as preproinsulin and progressively shorter COOH termini. The DNA was transcribed, the in vitro transcription products were translated in the wheat germ cell-free translation system, and the interaction of the resulting truncated polypeptides with signal recognition particle (SRP) and with microsomal membranes was analyzed. Truncations composed of 78 and 64 amino acids were translocated across the endoplasmic reticulum membrane, and translocation was found to be strictly co translational and SRP-dependent. Translocation efficiency at low membrane concentrations was reduced for these truncated molecules relative to full-length preproinsulin. Most significantly, translation of the 64-residue polypeptide was arrested by SRP after only 50 amino acids were polymerized. This suggests that the initial interaction of nascent secretory proteins with SRP occurs when only 10 residues of the signal peptide protrude from the large ribosomal subunit. PMID- 2185251 TI - Isolation, characterization, and expression in Escherichia coli of a cDNA encoding rat heme oxygenase-2. AB - In a recent study (Cruse, I., and Maines, M.D. (1988) J. Biol. Chem. 263, 3348 3353), we reported the isolation of a small cDNA fragment encoding a portion of heme oxygenase-2 through immunological screening of a rat testis cDNA library in lambda gt11. We have now used this 274-base pair (bp) cDNA fragment as a hybridization probe for rescreening of the same library, and have thereby recovered a number of additional positive isolates. Of these, three candidates of approximately 900, 1100, and 1300 bp, respectively, were subsequently subcloned and sequenced. Although differing in length, the sequences of these clones were found to be otherwise identical. Moreover, the length of isolate 18B, 1284 bp, corresponded well with that of the single mRNA species (approximately 1300-1350 nucleotides) detected through Northern blot hybridization analysis of rat testis total and poly(A)+RNA. This full- or near full-length cDNA encodes a 315-amino acid protein with a molecular weight of 35,757, in good agreement with the 36,000 estimated molecular weight of heme oxygenase-2. When expressed in Escherichia coli, cDNA encodes a protein that cross-reacts with heme oxygenase-2 antiserum (as assayed by Western immunoblotting) and yields high levels of heme oxygenase activity in bacterial soluble cell extracts. Finally, computer analysis of the heme oxygenase-2 cDNA sequence indicates that the predicted amino acid sequence and hydropathy profile of the heme oxygenase-2 protein exhibit similarity with heme oxygenase-1. PMID- 2185252 TI - Increased ferritin gene expression is associated with increased ribonucleotide reductase gene expression and the establishment of hydroxyurea resistance in mammalian cells. AB - In the present study, we show that hydroxyurea-inactivated ribonucleotide reductase protein M2 has a destabilized iron center, which readily releases iron. In addition, evidence is presented which indicates that single or multistep selection for hydroxyurea resistance, in a variety of mammalian cell lines, leads to alterations in the expression of the gene for the iron storage protein, ferritin. In all hydroxyurea-resistant cell lines examined, including human, hamster, rat, and mouse, there was an elevation in ferritin heavy (H)- and/or light (L)-mRNA levels, but no change in the corresponding gene copy number. A detailed analysis of ferritin expression in a hydroxyurea-resistant mouse L cell line showed that when compared to its wild type counterpart, there was an increase in H subunit concentration but no significant change in L subunit levels. The increased H/L subunit ratio was not brought about by specific changes in the rates of ferritin subunit biosynthesis, but rather resulted from changes in the post-translational stability of H subunits relative to L subunits in the resistant cell line compared to its parental wild type. Also, we show that treatment of cells with hydroxyurea results in an increased rate of ferritin biosynthesis in the absence of changes in H- or L-mRNA levels. These results indicate that the development of even low level hydroxyurea resistance in mammalian cells may require alterations in ferritin gene expression, and they show an interesting relationship between the expressions of two highly regulated activities, ribonucleotide reductase and ferritin. PMID- 2185253 TI - Specific transcription of Saccharomyces cerevisiae 35 S rDNA by RNA polymerase I in vitro. AB - Specific transcription of yeast 35 S rDNA by RNA polymerase I has been demonstrated using fractionated extracts prepared from whole cells of Saccharomyces cerevisiae. Determination of the 5'-nucleotides of the in vitro transcripts indicated that two apparent start sites, corresponding to the first (initiating) and fifth nucleotide of the in vivo transcript, were utilized. Production of the 35 S rDNA transcript in this system was not inhibited by alpha amanitin. Specific transcription of both the 35 S and 5 S rDNA sequences contained on the same template occurred simultaneously in these extracts. Sequential template competition experiments demonstrated that 35 S and 5 S rDNA transcription required different transcription factors. Specific antisera raised against the largest subunit of RNA polymerase I significantly inhibited synthesis of the 35 S rDNA transcript, but had a negligible effect on 5 S rRNA synthesis by RNA polymerase III. Additionally, this 35 S rDNA transcriptional activity was present in extracts prepared from a strain deficient in the mitochondrial RNA polymerase. Experiments using truncated rDNA templates showed that in vitro no more than 206 base pairs of the sequence upstream of the initiation site are required for maximal activity in this system; the enhancer element did not stimulate 35 S rDNA transcription. PMID- 2185254 TI - Relationship of c-myc gene copy number and gene expression: cellular effects of elevated c-myc protein. AB - The relationship between gene copy number and expression and cellular consequences of elevated levels of c-myc protein has been investigated using recombinant Chinese hamster ovary cell lines transfected with DNA coding for the murine c-myc gene. HC-8 and LC-5 recombinant cells carry approximately 800 and 50 copies of c-myc sequences, respectively, under control of an inducible heat shock promoter. Multivariate flow cytometric analysis and clonogenic assays were used to measure the relationship among c-myc expression, rate of DNA synthesis, and cell survival. Following heat exposure, maximally induced HC-8 cells produced approximately tenfold more c-myc protein than heated LC-5 cells, suggesting a close relationship between gene copy number and level of expression. However, considerable heterogeneity in the level and time of c-myc expression was observed following heat induction, even though the amounts of genomic c-myc were relatively constant. Heterogeneity in gene expression was not attributable to variation in heat induction methodologies and/or cell cycle phase distributions. The presence of high levels of recombinant c-myc protein was associated with a decreased rate of bromodeoxyuridine incorporation into DNA. High levels of c-myc protein in HC-8 cells were inversely correlated with cell survival postheating, suggesting that high levels of c-myc protein are incompatible with cell survival. PMID- 2185255 TI - Chromatographic analysis of chemical warfare agents. AB - The usefulness and applications of the particular types of chromatography in the analysis of chemical warfare agents have been reviewed. A major problem in the chromatographic analysis of chemical warfare agents is the collection and preparation of the samples. The importance of this problem differs for the various types of chromatography. Significant differences occur in the way in which samples are collected from air, water, soil, vegetables or animal organisms. The analyses are characterized by the main groups of chemical warfare agents, e.g., organophosphorus, vesicants, irritants, etc. Account has been taken of the relationships between their properties and the possibilities of their chromatographic analysis. The advantages and disadvantages of particular types of chromatography in the analysis of the particular groups and individual agents have been considered. The detectability of particular chemical warfare agents has been assessed, together with the separating efficiency for their mixtures. Examples of applications of chromatographic systems and conditions of chromatographing are summarized in tables. It is concluded that chromatography is a very useful tool in the analysis of chemical warfare agents; GC and TLC have the most advantageous properties, HPLC being slightly inferior. PMID- 2185256 TI - Isotope dilution gas chromatography-mass spectrometry in the determination of benzene, toluene, styrene and acrylonitrile in mainstream cigarette smoke. AB - A cryogenic trapping method with isotope dilution gas chromatography-mass spectrometry analysis has been developed for the determination of benzene, toluene, styrene and acrylonitrile in mainstream vapor phase cigarette smoke. The method is simple, direct, and quantitative. Vapor phase samples are collected cryogenically in a series of four traps following removal of the particulate phase with a Cambridge filter pad. For all four analytes, 75-85% of the total amounts recovered were found in the initial trap and less than 1% in the final trap. Assessment of instrumental precision by multiple injections of a sample gave relative standard deviations of less than 2%. Linear calibration for all analytes over the analysis range gave an r2 value greater than 0.99 with average relative standard deviations at the mean ranging from 1.4 to 8.2%. The cigarettes analyzed include a reference cigarette (Kentucky 1R4F), a commercial ultra-low "tar" mentholated cigarette, and two cigarettes that heat but do not burn tobacco. The values determined for the four analytes in the 1R4F samples are comparable to reported values of similar cigarettes. The cigarettes which heat rather than burn tobacco yield less of all four analytes compared to the other cigarettes in the study. PMID- 2185257 TI - Characterization of antibody reactivity to human T-cell lymphotropic virus types I and II using immunoblot and radioimmunoprecipitation assays. AB - We have characterized the immunoreactivity to human T-cell lymphotropic virus type I (HTLV-I) among 26,983 persons of various seroprevalence groups by using enzyme immunoassay, immunoblot (IB), and radioimmunoprecipitation assays (RIPA) in accordance with Public Health Service recommended guidelines for the interpretation of serologic test results for HTLV-I infection. IB-indeterminate serum specimens (n = 178) were reactive to HTLV-I gag proteins, and no serum contained only env reactivity. Overall, RIPA resolved 40% of IB-indeterminate serum samples; however, the probability that RIPA would confirm IB-indeterminate samples depended on the seroprevalence of the population tested. HTLV-I gag p19 only reactivity on IB was not a reliable marker of HTLV-I infection, while gag p24 reactivity on IB was clearly associated with positive seroreactive specimens. IB and RIPA tests did not clearly distinguish between HTLV-I and HTLV-II seroreactivities. These data emphasize that patterns of immunoreactivity to HTLV I antigens are dependent upon the seroprevalence of the risk groups tested. In addition, RIPA detected antibodies to env proteins present in low titer in a substantial number of IB gag-only reactive sera and resolved the HTLV-I antibody status of these sera. PMID- 2185258 TI - Rapid detection of bacteria in cerebrospinal fluid by immunofluorescence staining on membrane filters. AB - A filter-fluorescent-antibody (FFA) staining procedure was developed for detection of bacteria in cerebrospinal fluid (CSF). The sensitivity of this procedure was determined and compared with that of the slide Gram stain of centrifuged samples, latex agglutination, and a previously developed filter Gram stain. Serial 10-fold dilutions of filter-sterilized CSF seeded with logarithmic phase organisms were examined by each method and cultured to determine colony forming bacteria. The bacteria included Haemophilus influenzae type b; Neisseria meningitidis group B, C, and W135; Streptococcus pneumoniae types 6A and 23F; and group B Streptococcus species. FFA was found to be equal in sensitivity to the filter Gram stain (P greater than 0.30). Both filter-staining procedures had greater sensitivity than the slide Gram stain of centrifuged sediment (P less than 0.02) and latex agglutination (P less than 0.0001). Addition of human leukocytes at a concentration of 5 to 10 cells per oil immersion field did not decrease sensitivity of the FFA procedure, although background fluorescence increased. FFA is a rapid and dependable procedure for detection of low numbers of bacteria in CSF. Evaluation of FFA with clinical specimens is needed. PMID- 2185259 TI - Evidence for two types of cytotoxic necrotizing factor in human and animal clinical isolates of Escherichia coli. AB - We have characterized the in vitro and in vivo toxic properties of cell sonic extracts from 22 animal and human clinical isolates of Escherichia coli that caused both necrosis in the rabbit skin and multinucleation in tissue cultures, two toxic properties previously reported as being specific for E. coli cytotoxic necrotizing factor (CNF). Two distinct toxic phenotypes were observed. Type 1, which was displayed by originally described CNF strains, was characterized by extensive multinucleation and rounding of cells in HeLa cell culture assays, moderate necrosis in the rabbit skin test, and absence of necrosis in the mouse footpad test. Type 2, which has recently been shown to be associated with E. coli Vir plasmid, was characterized by moderate multinucleation, by polymorphism and elongation of HeLa cells, and by an intense necrotic response in both the rabbit skin test and the mouse footpad test. The distinction between the two cytotoxins accounting for these effects (CNF 1 and CNF 2), together with their partial relatedness, was confirmed by seroneutralization studies of both cytopathic effects and necrosis in the rabbit skin test. In addition, type 2 extracts were more lethal in the mouse intraperitoneal test and induced a moderate, although not totally repetitive, fluid accumulation in the ileal loop test. The original toxic properties of these recently recognized categories of E. coli strains, together with their association with enteritis and septicemia, suggest that these strains may play a significant role in pathology. PMID- 2185260 TI - Development of a highly specific and sensitive rubella immunoglobulin M antibody capture enzyme immunoassay that uses enzyme-labeled antigen. AB - An enzyme immunoassay (EIA) for serum immunoglobulin M (IgM) antibodies to rubella virus based on enzyme labeling of viral antigen was developed. The sensitivity of the EIA for the detection of recent rubella virus infection was evaluated by using 115 rubella-IgM-antibody-positive serum specimens, which were confirmed as positive by Rubazyme M (Abbott Diagnostics). In addition, 12 individuals, 2 of whom were exposed to rubella through vaccination and 10 of whom were exposed through natural infection, were studied, and the results were compared with those obtained by indirect EIA (Rubelisa M; Electro-Nucleonics, Inc.) and immunoblotting. The sensitivity of the newly developed EIA with sera from these individuals was 100%. Serum specimens from two patients indicated that the IgM antibodies were detected by the newly developed EIA at the same time as IgM antibodies were detected by immunoblotting and before positive reactions were detected by an indirect EIA. The reference population consisted of 564 healthy blood donors and hospitalized patients (150 serum specimens). In addition, 145 serum specimens commonly giving false-positive reactions in conventional rubella IgM EIAs were studied. With these specimens, no false-positive reactions were observed. Positive IgM responses, which could not be confirmed by immunoblotting, were observed in two samples from the reference population. However, these two samples were rubella IgG positive. The overall specificity of the EIA was 99.8%. PMID- 2185261 TI - Rapid detection of respiratory syncytial virus in nasopharyngeal specimens obtained with the rhinoprobe scraper. AB - We compared the Rhinoprobe scraping technique for collection of superficial nasal mucosa epithelial cells and rapid detection of respiratory syncytial virus by immunofluorescence with paired, swab-collected specimens for virus culture from 1,257 infants and children with acute respiratory infections. Compared with viral culture as the reference test, the sensitivity, specificity, and accuracy of the immunofluorescence test were 83.6, 93.6, and 91.3%, respectively. We found the Rhinoprobe method safe, easy to use, and helpful in obtaining large quantities of epithelial cells for detection of respiratory syncytial virus and other respiratory viruses. PMID- 2185262 TI - Virulence-related genes in ColV plasmids of Escherichia coli isolated from human blood and intestines. AB - DNA probes for the colicin V, traT, iss, and iu genes were used in this study of four representative ColV plasmids together with 200 Escherichia coli strains isolated from the stools of patients with diarrhea and 146 E. coli strains isolated from the blood of patients with bacteremia. The study indicated that the ColV plasmids are heterogeneous. Southern and colony hybridization analyses showed that in most of the colicin V-producing intestinal E. coli strains, the colicin V genes are located in the chromosome (14 of 16); in most of the colicin V-producing E. coli strains isolated from the blood, they are located in plasmids (18 of 22). In both intestinal and blood E. coli isolates, the traT, iss, and aerobactin receptor genes were present at similar frequencies, but the frequency of the aerobactin synthesis genes was significantly different. The aerobactin receptor gene was present in 25% of the intestinal E. coli strains that lack the aerobactin synthesis gene. In the blood isolates, the aerobactin synthesis and receptor genes were present at almost equal frequencies. Among the colicin V producing isolates, the iss, traT, and iu genes were present in 95.5, 86.4, and 90.9% of the blood isolates and in only 68.8, 43.8, and 81.3% of the intestinal isolates, respectively. The ColV plasmids from blood isolates that were tested for the presence of traT, iss, and iu genes were homogeneous and had DNA sequences that hybridized with each of the probes. On the other hand, the two intestinal strains containing ColV genes in a plasmid were heterogeneous in regard to the carriage of these genes. The presence of ColV is not restricted to specific O types. PMID- 2185263 TI - Cluster of antibiotic-resistant Salmonella enteritidis infections in the Central African Republic. AB - Salmonella enteritidis strains which are multiply resistant to antimicrobial agents were isolated from the blood of 12 patients hospitalized at the Institut Pasteur of Bangui, Central African Republic, during a 4.5-month period. The lack of gas production in Kligler-Hajna medium initially suggested Salmonella typhi, but isolates were confirmed as unusual S. enteritidis strains. The occurrence of these unique strains in an unusual site of infection may indicate an epidemic due to an unusually invasive and resistant strain of S. enteritidis. Some variation in plasmid profile and susceptibility to antimicrobial agents was noted, possibly reflecting antibiotic pressures existing in the Central African Republic. All isolates were of the same bacteriophage lysis pattern, unlike patterns documented for recent U.S. and European isolates of S. enteritidis. PMID- 2185264 TI - Effect of patient characteristics on performance of an enzyme immunoassay for detecting cervical Chlamydia trachomatis infection. AB - We compared the performance of a commercial enzyme immunoassay (EIA) (Chlamydiazyme; Abbott Diagnostics, North Chicago, Ill.) with that of cell culture for the detection of Chlamydia trachomatis cervical infection in 1,417 women attending public health clinics. Confirmatory chlamydial testing by a direct fluorescent-antibody test (MicroTrak; Syva Co., Palo Alto, Calif.) was performed on specimens from women who had positive EIAs. Overall, only 57% of women who had a positive chlamydial test by cell culture were also positive by EIA. We noted a strong association between the number of chlamydial inclusions in cell culture and a positive EIA outcome. The proportion of culture-positive women who also had a positive EIA declined with age and a history of previous sexually transmitted disease and increased among oral contraceptive users. The results of direct fluorescent-antibody confirmatory testing suggested that cell culture was also insensitive for the detection of C. trachomatis infection. Our observations demonstrate that the performance of the chlamydial EIA may vary greatly with individual patient characteristics and that the utility of EIA as a screening test may be limited, especially in older women. PMID- 2185265 TI - Comparison of three assay systems for detection of enterotoxigenic Escherichia coli heat-stable enterotoxin. AB - In this study, a commercial DNA-DNA hybridization kit for the detection of Escherichia coli heat-stable enterotoxin is compared with a competitive enzyme linked immunosorbent assay (ELISA) and the suckling mouse bioassay. Taking the suckling mouse assay as the "gold standard," the gene probe was the more specific and the ELISA was the more sensitive of the assays. The ELISA and the suckling mouse test are semiquantitative. The ELISA was the most rapid method, most amenable to automation, and most suitable for the examination of large numbers of specimens. The gene probe is particularly applicable in relatively primitive laboratory conditions. The suckling mouse assay was the least suitable system for the examination of large numbers of specimens. PMID- 2185266 TI - Effect of altered headspace atmosphere on yield and speed of detection of the Oxoid Signal blood culture system versus the BACTEC radiometric system. AB - The one-bottle Oxoid Signal blood culture system altered to provide a more aerobic bottle headspace was reassessed in a comparative study versus the two bottle BACTEC radiometric system in 5,426 blood cultures. The BACTEC system detected more microorganisms (P less than 0.02), particularly anaerobes (P less than 0.05) and fungi (P less than 0.05). PMID- 2185267 TI - Urease-negative Nocardia asteroides causing cutaneous nocardiosis. AB - We report a case of cutaneous nocardiosis, caused by a urease-negative strain of Nocardia asteroides, in a patient who had undergone long-term corticosteroid therapy. The microbiological characteristics of the isolate were typical of N. asteroides except for the failure of the isolate to hydrolyze urea. During the course of routine identification, laboratory specialists should be aware of the occasional occurrence of atypical strains of N. asteroides. PMID- 2185268 TI - Temperature range for growth of Escherichia coli serotype O157:H7 and selected coliforms in E. coli medium. AB - Escherichia coli serotype O157H:7 and five other fecal and nonfecal coliforms were tested for minimum and maximum temperatures for growth in E. coli medium by using a temperature gradient incubator with a mean temperature increment of 1.67 degrees C (+/- 0.392). The temperature range for growth of E. coli O157:H7 is inconsistent with that of other fecal coliforms, suggesting that this pathogen is excluded with standard enumeration procedures used for foods and water. PMID- 2185270 TI - Evaluation of different techniques for detection of virulence in Yersinia enterocolitica. PMID- 2185269 TI - Isolation of a previously undescribed rickettsia from an aborted bovine fetus. AB - A previously undescribed obligate intracellular bacterium was isolated from an aborted bovine fetus. The organism was resistant to penicillin, replicated within cytoplasmic vacuoles, exhibited structural characteristics compatible with the rickettsias, and shared antigenic determinants with Cowdria ruminantium. PMID- 2185271 TI - L-fucosidase treatment blocks myelin phagocytosis by macrophages in vitro. AB - Myelin phagocytosis in nerves undergoing Wallerian degeneration has been shown to depend on their invasion by non-resident, hematogenous macrophages. This process can be studied in vitro using organ cultures of peripheral nerves exposed to cultured peritoneal macrophages. The present report concerns the role of cell surface carbohydrates in the invasion of degenerating nerves and in the recognition and ingestion of myelin by the phagocytic cells. Additional experiments explored the effect of pH, calcium and cytochalasin D on myelin phagocytosis. Organ cultures with peritoneal macrophages were treated with 14 simple or complex sugars or with eight sugar-splitting enzymes. Macrophage invasion was diminished by many simple or complex sugars, but exposure to sugars had no effect on the recognition or ingestion of myelin by the invading macrophages. Macrophage invasion was abolished upon treatment with beta mannosidase. Exposure to L-fucosidase abolished the myelin phagocytic capacity of invading macrophages completely without affecting their capacity to ingest carbon or latex particles. The results indicate that the phagocytosis of myelin by macrophages is an L-fucosidase-sensitive process, probably by interaction with their complement receptor type C3. PMID- 2185272 TI - Alpha 1-antitrypsin deficiency, emphysema, and liver disease. Genetic basis and strategies for therapy. PMID- 2185273 TI - Altered expression of gangliosides in erythrocytes of paroxysmal nocturnal hemoglobinuria. AB - In paroxysmal nocturnal hemoglobinuria (PNH), impaired glycosyl phosphatidylinositol (PI)-anchoring of membrane proteins such as decay accelerating factor has been known to lead to increased susceptibility to complement. Moreover, abnormal expression of non-PI-anchoring glycoproteins such as C3b/C4b receptor (CR1) or glycophorin-alpha also has been shown in PNH. Therefore, we biochemically analyzed glycosphingolipids (GSL) as one of the membrane glycoconjugates of PNH erythrocytes. Erythrocytes of all seven PNH patients showed altered expression of sialosyl GSL (gangliosides) as compared with the control erythrocytes of healthy donors. Both a sialosylparagloboside (IV6NeuAc-nLc4Cer) among four major gangliosides and some minor gangliosides in normal erythrocytes variably disappeared in erythrocytes from the peripheral blood of PNH patients. As one of the possible mechanisms of altered expression of gangliosides in PNH erythrocytes, structural analysis suggested impaired sialylation of GSL. These results suggest not only the altered metabolism of gangliosides in PNH erythrocytes, but also a metabolic disorder of membrane glycoconjugates as a new feature of PNH. PMID- 2185274 TI - Human seminal clusterin (SP-40,40). Isolation and characterization. AB - Molecular cloning of the human complement inhibitor SP-40,40, has revealed strong homology to a major rat and ram Sertoli cell product, sulfated glycoprotein-2, known also as clusterin. This study reports the purification and characterization of human seminal clusterin. Two-dimensional gel electrophoresis revealed charge differences between clusterin purified from semen and the serum-derived material. Both preparations demonstrate comparable hemagglutination (clustering) activity and inhibition of C5b-6 initiated hemolysis. The average clusterin concentration in normal seminal plasma is considerably higher than that found in serum. Mean seminal plasma clusterin concentrations were significantly lower in azoospermia caused by obstruction or seminiferous tubule failure than with oligospermia or normospermia. Only men with vasal agenesis had undetectable seminal clusterin, suggesting that some of the seminal clusterin is produced by the seminal vesicles. Immunofluorescence of human spermatozoa revealed that clusterin was detected on 10% of spermatozoa, predominantly those that were immature or had abnormal morphology. A pilot study of 25 patients suggests that seminal clusterin concentration, together with sperm motility and morphology, is correlated with the fertilization rate in vitro. The function of seminal clusterin is unknown. Its extensive distribution in the male genital tract and its high concentration in seminal plasma suggests an important role in male fertility. PMID- 2185275 TI - Pathogenesis of an experimental model of Goodpasture's hemorrhagic pneumonitis. AB - The mechanisms that allow circulating basement membrane antibodies (Ab) to interact with the alveolar basement membrane (ABM) inducing Goodpasture's hemorrhagic pneumonitis are unknown. In laboratory animals the ABM is inaccessible to phlogogenic amounts of ABM Ab unless the permeability of the unfenestrated alveolar endothelium is increased. This study was designed to test the hypothesis that in the mouse polypeptide mediators, generated by activated lymphoid cells or cells infected by viruses, contribute to the pathogenesis of passive Goodpasture's hemorrhagic pneumonitis. In naive mice that received rabbit ABM Ab, these bound to the glomerular basement membrane but not to the ABM and their lungs were normal. In the lungs of mice injected with human recombinant IL 2 and IFN-alpha specific binding of ABM IgG, C3, and fibrinogen to the ABM, diffuse and severe erythrocyte extravasation, and accumulation of mononuclear and polymorphonuclear leukocytes were constantly observed. ABM Ab and IL-2 or ABM Ab and IFN-alpha did not produce comparable effects. Mice injected only with IL-2 and IFN-alpha had enlarged, edematous lungs without pulmonary hemorrhages. The results show that the synergism of IL-2 and IFN-alpha convert the lung into a preferential target for AMB Ab, suggesting that cytokines may have a role in the pathogenesis of human Goodpasture's pneumonitis. PMID- 2185276 TI - Effect of adenosine1-receptor blockade on renin release from rabbit isolated perfused juxtaglomerular apparatus. AB - Adenosine has been proposed to act within the juxtaglomerular apparatus (JGA) as a mediator of the inhibition of renin secretion produced by a high NaCl concentration at the macula densa. To test this hypothesis, we studied the effects of the adenosine1 (A1)-receptor blocker 8-cyclopentyl-1,3 dipropylxanthine (CPX) on renin release from single isolated rabbit JGAs with macula densa perfused. The A1-receptor agonist, N6-cyclohexyladenosine (CHA), applied in the bathing solution at 10(-7) M, was found to inhibit renin secretion, an effect that was completely blocked by adding CPX (10(-5) M) to the bath. Applied to the lumen, 10(-5) M CPX produced a modest stimulation of renin secretion rates suppressed by a high NaCl concentration at the macula densa (P less than 0.05). The effect of changing luminal NaCl concentration on renin secretion rate was examined in the presence of CPX (10(-7) and 10(-5) M) in the bathing solution and in vehicle control experiments. The control response to increasing luminal NaCl concentration was a marked suppression of renin secretion, that was maintained as long as luminal NaCl concentration was high and was promptly reversible when concentration was lowered. CPX did not alter renin release when luminal NaCl was low, but diminished the reduction caused by high NaCl (P less than 0.01). It is concluded that A1-receptors are located within the JGA, and that A1-receptor activation inhibits renin release. A high NaCl concentration at the macula densa appears to influence A1-receptor activation, but a low NaCl concentration does not. The findings support participation of adenosine in macula densa control of renin secretion. PMID- 2185277 TI - Effects of acute hyperglycemia on myocardial glycolytic activity in humans. AB - The effects of hyperglycemia on myocardial glucose metabolism were investigated in seven healthy male subjects (age 24 +/- 4 yr). [6-14C]Glucose and [U 13C]lactate were infused as tracers. Circulating glucose was elevated to two hyperglycemic levels using a clamp technique for 1 h at each level. The mean arterial glucose concentration was 4.95 +/- 0.29 (control), 8.33 +/- 0.31 and 10.84 +/- 0.60 mumols/ml, respectively. Glucose extraction increased significantly from control (0.15 +/- 0.13 mumols/ml) during each level of the glucose clamp (0.28 +/- 0.12, P less than 0.02, and 0.54 +/- 0.14 mumols/ml, P less than 0.005, respectively). Myocardial production of 14CO2 showed that during control 9 +/- 10% of exogenous glucose was oxidized immediately upon extraction. Despite a significant increase in the amount of exogenous glucose oxidized with level II hyperglycemia, it represented only 32 +/- 10% of the glucose extracted. [13C]Lactate analysis showed that the myocardium was releasing lactate; during control 40 +/- 30% of this lactate was derived from exogenous glucose and during hyperglycemia this value increased to 97 +/- 37% (P less than 0.005). Thus, these data show that during short-term hyperglycemia, myocardial glucose extraction is enhanced. However, despite increases in exogenous glucose oxidation and the contribution of exogenous glucose to lactate release, the majority of the extracted glucose (i.e., 57%) is probably stored as glycogen. PMID- 2185278 TI - A defect in sodium-dependent amino acid uptake in diabetic rabbit peripheral nerve. Correction by an aldose reductase inhibitor or myo-inositol administration. AB - A myo-inositol-related defect in nerve sodium-potassium ATPase activity in experimental diabetes has been suggested as a possible pathogenetic factor in diabetic neuropathy. Because the sodium-potassium ATPase is essential for other sodium-cotransport systems, and because myo-inositol-derived phosphoinositide metabolites regulate multiple membrane transport processes, sodium gradient dependent amino acid uptake was examined in vitro in endoneurial preparations derived from nondiabetic and 14-d alloxan diabetic rabbits. Untreated alloxan diabetes reduced endoneurial sodium-gradient dependent uptake of the nonmetabolized amino acid 2-aminoisobutyric acid by greater than 50%. Administration of an aldose reductase inhibitor prevented reductions in both nerve myo-inositol content and endoneurial sodium-dependent 2-aminoisobutyric acid uptake. Myo-inositol supplementation that produced a transient pharmacological elevation in plasma myo-inositol concentration, but did not raise nerve myo-inositol content, reproduced the effect of the aldose reductase inhibitor on endoneurial sodium-dependent 2-aminoisobutyric acid uptake. Phorbol myristate acetate, which acutely normalizes sodium-potassium ATPase activity in diabetic nerve, did not acutely correct 2-aminoisobutyric uptake when added in vitro. These data suggest that depletion of a small myo-inositol pool may be implicated in the pathogenesis of defects in amino acid uptake in diabetic nerve and that rapid correction of sodium-potassium ATPase activity with protein kinase C agonists in vitro does not acutely normalize sodium-dependent 2-aminoisobutyric acid uptake. PMID- 2185279 TI - An insulin-induced DNA-binding protein for the human growth hormone gene. AB - The control of gene transcription is usually mediated by transacting transcriptional factors that bind to upstream regulatory elements. As insulin regulates transcription of the growth hormone (GH) gene, we tested nuclear extracts from unstimulated and insulin-stimulated Chinese hamster ovarian (CHO) cells for binding to four human GH (hGH) gene promoter oligonucleotide fragments identified as target-binding sequences by DNAse I footprinting. Using a mobility shift assay, an insulin-induced DNA-binding protein was identified. This protein binds to two upstream overlapping oligonucleotide sequences. Binding activity is present at low levels in unstimulated CHO cells and is stimulated by insulin treatment with a time course suggesting that protein synthesis is required. Incubation of the cells with cycloheximide and puromycin confirmed that de novo protein synthesis is necessary for the increased binding activity. Competition with excess unlabeled specific competitor oligonucleotides prevented binding, while unrelated similar-sized oligonucleotides failed to compete for binding, indicating that the observed DNA-protein complex formation is specific. A protein of approximately 70-80 kD was detected by gradient gel electrophoresis. In conclusion, insulin-mediated DNA-protein binding has been identified on the upstream hGH promoter, suggesting a trans-active role for insulin in mediating polypeptide hormone gene expression. PMID- 2185280 TI - Development of a sensitive enzyme immunoassay for OPC-7251, a novel antimicrobial agent for percutaneous application. AB - A sensitive enzyme immunoassay for OPC-7251, a novel pyridone carboxylic acid antimicrobial agent, was developed and applied for the determination of human plasma levels. OPC-7251 was coupled to bovine serum albumin through a formation of N-hydroxysuccinimide ester. By immunization of rabbits, highly specific antiserum was raised. Using the antiserum and beta-D-galactosidase-labeled hapten, the homologous assay system allowed the detection of 2 pg of this compound. Plasma samples were precisely analyzed down to the minimum value of 200 pg/ml after heat treatment. The system was further validated by the recovery test and correlation with the HPLC analyses. Percutaneous application of 10 g of 1% OPC-7251 cream to healthy volunteers resulted in the peak plasma value of 1.6 ng/ml about 8 hours after dosing, indicating extremely low absorption efficiency through a transdermal system. PMID- 2185281 TI - Guidelines on oral anticoagulation: second edition. British Society for Haematology. British Committee for Standards in Haematology. Haemostasis and Thrombosis Task Force. PMID- 2185283 TI - Immunohistochemical and electron microscopic findings in benign fibroepithelial vaginal polyps. AB - Eleven classic benign "fibroepithelial polyps" of the vagina were examined using a panel of immunocytochemical agents. Two were also examined electron microscopically. In all cases the stellate and multinucleate stromal cells characteristic of these lesions stained strongly for desmin, indicating muscle intermediate filament production. In common with uterine fibroleiomyomata, numerous mast cells were also often seen. Myoglobin staining was negative. Electron microscopical examination confirmed that the stromal cells contained abundant thin filaments with focal densities and also showed the ultrastructural features usually associated with myofibroblasts. It is concluded that these tumours would be better designated polypoid myofibroblastomas in view of the above findings. PMID- 2185284 TI - Coagulase testing compared with commercial kits for routinely identifying Staphylococcus aureus. AB - Five commercial Staphylococcus aureus identification kits--Staphaurex (Wellcome), Staphylase (Oxoid), Staphyslide (bioMerieux), Biostaph (Medlabs) and Bacto Latex (Difco)--were evaluated for the routine identification of S aureus from primary plates in the routine microbiology laboratory. Comparison was made with two methods of tube coagulase testing and five slide methods for detecting clumping factor (slide coagulase testing). Performances were assessed for two groups of organisms, staphylococcal species alone and a combined staphylococcal and non staphylococcal species group. The effects of growth on selective media and storage of isolates at room temperature and 4 degrees C were investigated. Selective media cannot be recommended, nor can storage of isolates before testing. Ranked according to efficiency value with the combined staphylococcal and non-staphylococcal species group, the kits and coagulase methods performed as follows (the figures in parentheses are the efficiency values for the staphylococcal group alone): tube coagulase reference method 100% (100%), tube coagulase SJH method 99% (99%), Staphaurex 94% (97%), Staphylase 93% (96%), slide coagulase method No 4 93% (94%), slide coagulase method No 5 93% (93%), Bacto Latex 92% (95%), Staphyslide 92% (95%), and Biostaph 87% (91%). It is concluded that a commercial S aureus identification kit should not replace tube coagulase testing for the routine identification of the organism from primary plates and that, even the kits with the best performances, have little advantage over a good slide coagulase test method. PMID- 2185282 TI - Review: assessment of cell proliferation in histological material. PMID- 2185285 TI - Technical improvements in the immunoperoxidase study of renal biopsy specimens. AB - Sixty five renal biopsy specimens were used to compare a direct immunofluorescence technique on frozen sections with immunoperoxidase techniques on paraffin wax sections. For the immunoperoxidase techniques, dewaxed sections were treated with protease at 37 degrees C. Sections were examined at intervals on a microscope and digestion was stopped when plasma was removed from glomerular capillary loops. This permitted intense staining of immunoproteins on immunoperoxidase. There was agreement between immunoperoxidase and immunofluorescence in the staining for IgG, IgA, and IgM in 50 biopsy specimens and discordant findings did not affect the diagnosis. Immunoperoxidase did not detect C3 in 16 biopsy specimens. Findings with antiserum to another complement component, C9, detected by immunoperoxidase correlated with C3 findings detected by immunofluorescence in 17 biopsy specimens. It is concluded that microscopical observation of the progress of digestion permits optimal staining by immunoperoxidase methods, thus overcoming the problem of variability in proteolytic digestion of sections. Inconsistency in the demonstration of complement deposition can be avoided by staining for C9 rather than C3. PMID- 2185286 TI - Leukaemic phase of mantle zone (intermediate) lymphoma: its characterisation in 11 cases. PMID- 2185287 TI - Predictors of death following ICU discharge. AB - In order to study possible predictors of early after-discharge mortality (EADM), 700 consecutive patients discharged alive from three intensive care units (ICUs) were followed up 2 months after their admission. The observed mortality was 7.3%. Univariate analysis indicated a strong statistically significant association of the following variables with mortality: initial simplified acute physiological score (SAPS) greater than 10, therapeutic intervention score in the first 24 h of admission greater than 20, age greater than or equal to 65, length of stay in the ICU greater than 10 days, and low educational level. The multiple logistic regression analysis included as predictive independent variables the SAPS, organs or systems failure, age, and length of stay. The model built upon these four variables was able to identify a group of patients at high risk (21-46%) of EADM. We conclude that some simple variables can be used as useful markers of patients groups at high risk of EADM. PMID- 2185288 TI - Delivering CPAP with a siemens Servo 900B ventilator. PMID- 2185289 TI - Paying the piper--the linkage of alveolar ventilation to alveolar pressure. PMID- 2185290 TI - Auto-PEEP and dynamic hyperinflation in COPD patients during controlled mechanical ventilation and high frequency jet ventilation. AB - We investigated the levels of auto-PEEP and dynamic hyperinflation during high frequency jet ventilation (HFJV) and controlled mechanical ventilation (CMV) in six patients with chronic obstructive pulmonary disease within the first 36 h of acute exacerbation. The comparative evaluation was performed at similar conditions of gas exchange in HFJV and CMV: PaO2 77.6 +/- 11 mmHg vs 80.8 +/- 12 mmHg; PaCO2 46.8 +/- 2.5 mmHg vs 47 +/- 2.8 mmHg; pH 7.38 vs 7.38. In this situation, the values of auto-PEEP and dynamic hyperinflation, expressed as delta over the apneic functional residual capacity (FRC) did not differ: (auto-PEEPHFJV 8.9 +/- 3.8 cmH2O; auto-PEEPCMV 8.8 +/- 4.7 cmH2O; delta FRCHFJV 0.56 +/- 0.19 l; delta FRCCMV 0.54 +/- 0.2 l). This result suggests that, with a suitable machine setting and similar gas exchanges, HFJV produces the same level of auto-PEEP and dynamic hyperinflation as CMV in patients with chronic obstructive pulmonary disease. PMID- 2185291 TI - The effects of graded administration of positive end expiratory pressure on the fluid filtration rate in isolated rabbit lungs, using normal lungs, hydrostatic oedema lungs and oleic acid induced oedema. AB - The influence of positive end expiratory pressure (PEEP) on the fluid filtration rate (FFR) in the pulmonary circulation has been the subject of considerable investigation but data are conflicting. We studied twenty-nine isolated rabbit lung preparations, FFR was sensed by a force transducer. Autologous blood was used to prime the perfusion circuit. Hydrostatic oedema was achieved by increasing the left atrial pressure to 16 mmHg. In order to bring about increased membrane permeability oleic acid was injected through the pulmonary artery. Increasing and decreasing levels of PEEP at 0, 5, 10 and 15 cm H2O were each used for ten minutes in each of three experimental models. The FFR, pH, mean pulmonary arterial pressure (MPAP), mean left atrial pressure (MLAP), PaO2, PaCO2 and oncotic pressure were measured in each experiment. There was a significant correlation between PEEP and FFR (+0.94) in non-oedema lungs. With no PEEP the FFR was 0 g/min and with 15 cm of PEEP it increased to 0.07 g/min, on removing the PEEP the FFR returned to 0 g/min. In the hydrostatic lung oedema model the correlation was also significant but negative (r = -0.94). With no PEEP the FFR was 0.33 g/min, with PEEP of 15 cm H2O it decreased to 0.08 g/min. No correlation between PEEP and FFR was found in the oleic acid preparation. In the normal lung PEEP increases capillary hydrostatic pressure and total lung vascular area and decreases interstitial pressure. It is by these mechanisms that PEEP causes an increase in FFR. In the hydrostatic oedema model PEEP decreases FFR by increasing the interstitial pressure and by decreasing the total lung vascular area. In the oleic acid preparation the coefficient of filtration is so large that small changes in pressure or vascular area do not modify the FFR. We suggest that PEEP may be beneficial by decreasing FFR in hydrostatic lung oedema, but it may increase the FFR in the normal lung, while having no effect in oleic acid lung injury. PMID- 2185292 TI - Studies of the mechanism of angiotensin-converting enzyme (ACE) inhibitor associated angioedema: the effect of an ACE inhibitor on cutaneous responses to bradykinin, codeine, and histamine. AB - To understand better the mechanism of angiotensin-converting enzyme (ACE) inhibitor-associated angioedema, we studied the effects of ACE-inhibitor treatment on wheal-and-flare responses to histamine, codeine, and bradykinin in 10 normal subjects. No change in the size of wheal-and-flare reactions to histamine occurred, but the size of wheal reactions to codeine and bradykinin increased in all study subjects after ingesting the ACE inhibitor, captopril. Five of 10 study subjects developed flushing reactions after ACE-inhibitor treatment. We conclude that inhibition of bradykinin metabolism by ACE inhibitors is the probable cause of ACE inhibitor-related angioedema and that substance P is not the predominant mediator in this process. PMID- 2185293 TI - Allergen-induced increase of eosinophil cationic protein in nasal lavage fluid: effect of the glucocorticoid budesonide. AB - It was our aim to study the effect of nasal allergen provocation on the concentration of eosinophil cationic protein (ECP) in nasal lavage fluid, with and without glucocorticoid pretreatment. Twenty grass-pollen sensitive volunteers were provoked outside the pollen season on 2 consecutive days after pretreatment for 2 weeks with the glucocorticoid, budesonide, as a nasal spray (400 micrograms/day) and with placebo with a double-blind, crossover design. Nasal lavage fluid was repeatedly collected during a 10-hour period to study both early and late-phase responses. 99mTechnetium-albumin was added to the lavage fluid, making it possible to calculate the amount of secretion and the degree of dilution. The results were as follows: (1) There was no correlation between ECP concentration and dilution factor in the individual samples. (2) The mean concentration of ECP in lavage fluid from untreated, prechallenge noses was 400 micrograms/L. (3) The ECP level did not increase during the early phase response. (4) There was a late occurring increase in the ECP concentration (6 to 24 hours). (5) This increase was completely inhibited by budesonide pretreatment. (6) The glucocorticoid therapy also reduced the prechallenge ECP concentration. In conclusion, allergen provocation in the nose results in a late occurring increase of ECP in nasal lavage fluid, and one of the therapeutic effects of topical glucocorticoid therapy may be an inhibition of the allergen-induced increase of this cytotoxic molecule. PMID- 2185294 TI - Thymopentin therapy reduces the clinical severity of atopic dermatitis. AB - One hundred patients with moderate to severe atopic dermatitis were entered into a two-center, double-blind trial. Patients were randomized to receive either thymopentin (Timunox, n = 48) or placebo (n = 52), administered as daily subcutaneous injections for 6 weeks. Clinical extent of disease and severity parameters were measured at baseline and at regular time intervals during the study. Both the placebo- and thymopentin-treated groups demonstrated a progressive and statistically significant (p less than 0.001) decline in the overall severity of their disease, but reduction in the clinical severity score was higher in the thymopentin-treated group and statistically significant (p = 0.04) in comparison with the placebo-treated group after 6 weeks of treatment. Of the individual symptoms comprising the total severity score, pruritus (p = 0.02) and erythema (p = 0.04) were reduced significantly when thymopentin therapy was compared to placebo therapy. In addition, both the extent of body involvement and severity index (a combined severity/extent index) were significantly reduced after 6 weeks in the thymopentin-treated group in comparison to the placebo treated group (p = 0.04). There were no serious adverse experiences in either treatment group. We conclude that treatment with thymopentin is safe and offers significant therapeutic promise for atopic dermatitis. PMID- 2185295 TI - Improving medication prescribing and utilization in the nursing home. AB - There is ample and compelling evidence to suggest that medications are frequently used inappropriately in the nursing home. The occurrence of avoidable adverse drug reactions is the most serious consequence of inappropriate prescribing; economic implications are also of interest. With increasing concern over the quality of care in nursing homes, and with the revision of regulations governing such care by the Health Care Financing Administration, it is important to consider the experience thus far in monitoring and improving drug use in nursing homes. A number of studies have investigated approaches designed to reduce inappropriate prescribing and drug utilization in this setting. In contrast to the wide range of approaches that have been evaluated and implemented in the hospital setting, interventions in the nursing home have centered primarily around consultant-pharmacist activities. Although these activities are now federally mandated in all nursing homes, there is little evidence from adequately controlled studies to document their impact or cost-effectiveness. By contrast, face-to-face educational interventions directed at physicians ("academic detailing") have been shown to be effective in improving prescribing for some medications. The prominent role played by the nursing staff in the utilization of many medications in the nursing home implies that an educational intervention excluding nursing staff would be insufficient to influence drug utilization positively in many situations (eg, psychoactive medications and laxatives). Future research efforts must pay greater attention to adequate study design considerations as well as to the clinical outcomes of such interventions and their cost-effectiveness. PMID- 2185296 TI - Genetic factors in Alzheimer's disease. PMID- 2185297 TI - Assessment of hepatic function. Comparison of caffeine clearance in serum and saliva during the day and at night. AB - Hepatic microsomal function was assessed by a caffeine clearance test at night and during the day using saliva and serum samples obtained simultaneously. In 26 patients with cirrhosis, 21 patients with noncirrhotic liver disease and 15 control subjects caffeine elimination correlated well during the day and at night (r = 0.915 for serum and 0.917 for saliva). The correlation coefficients for caffeine clearance in saliva and serum were 0.940 during the day and 0.963 overnight. In the cirrhotic patients, clearance differed significantly from noncirrhotic liver disease and controls in saliva samples overnight: 0.51 +/- 0.45 ml/min per kg versus 0.91 +/- 0.44 and 1.41 +/- 0.56, respectively. Comparable results were obtained for serum clearance overnight and clearances during the day. Serum and saliva clearances at night correlated well with the aminopyrine breath test (rs = 0.884 and 0.907, respectively). Overnight caffeine clearance in saliva might be a simple useful method for assessing progression and prognosis of liver disease. PMID- 2185298 TI - A randomised prospective trial comparing daily paracentesis and intravenous albumin with recirculation in diuretic refractory ascites. AB - We report a randomised trial in 40 consecutive patients with diuretic refractory ascites comparing our standard therapy of ascites recirculation (Rhodiascit apparatus) with the newly proposed method of daily paracentesis (3-4 litre) and intravenous albumin infusion. A mean of five (range 2-13) paracenteses removed 13.3 (2.0-36.0) l of ascites. 12 (5-32) h of recirculation produced 6.0 (2.0 12.0) l of waste. A significant diuresis occurred in 14 recirculation patients compared to four treated by paracentesis. No significant changes in electrolyte levels or renal function occurred. Complications were commoner with paracentesis (12) than with recirculation (5). Following recirculation, 18 patients were discharged after 7 (2-21) days; significantly (p less than 0.04) shorter than after paracentesis (11 (4-34) days, 16 discharges). Ascites reaccumulation and survival were identical in both groups. Fewer complications, shorter hospital stay and lower consumables costs (recirculation 240 pounds, paracentesis 400 pounds) make ascites recirculation an attractive therapeutic option to daily paracentesis and intravenous albumin in diuretic refractory ascites. PMID- 2185299 TI - Haemodynamic effect of triglycyl-lysine-vasopressin (glypressin) on intravascular oesophageal variceal pressure in patients with cirrhosis. A randomized placebo controlled trial. AB - A double-blind random administration of 2 mg glypressin intravenously (i.v.) or placebo was given to 20 volunteer patients suffering from liver cirrhosis with portal hypertension and oesophageal varices. Experimental protocol required two basal intravascular oesophageal variceal pressure (IOVP) measurements, before and after bolus i.v. drug injection. The second measurement was taken as reference to determine whether the treatment was effective. Other measurements were taken 1, 3, 5 and 10 min after drug administration. The fall in IOVP at 3, 5 and 10 min in the patients who had been administered glypressin proved statistically significant (p less than 0.01) with mean percentage variations of -22.3%, -24.4% and -27.9%, respectively. In conclusion, the administration of glypressin in portal hypertensive patients brought about a marked reduction in transmural oesophageal variceal pressure in over 70% of the cases. This decrease may prove to be of clinical importance both as a first line therapy and as a possible aid to emergency sclerotherapy in the presence of active variceal bleeding. PMID- 2185300 TI - The lung in patients with cirrhosis. AB - To summarize, nowadays it seems clear that in patients with cirrhosis: (a) the pulmonary circulation is usually markedly dilated. (b) This vasodilation is due to a loss of vascular tone and it is characterized by a poor (or even absent) vascular reactivity in front of the hypoxic stimulus. (c) This abnormal behaviour of the pulmonary circulation results in VA/Q mismatching (basically perfusion of low VA/Q units) independently of airway disease, and may lower arterial PO2. (d) In the most severe cases, shunt (and perhaps O2 diffusion limitation) is becoming progressively more important. (e) The high cardiac output and minute ventilation of these patients minimize or prevent the appearance of arterial hypoxemia at rest. (f) The fall in arterial PO2 during exercise is not due to a deterioration of the degree of VA/Q mismatching seen at rest nor to any limitation in the diffusion of oxygen. It is caused by the relative 'normalization' (with respect to the metabolic demands) of the haemodynamic and ventilatory status of the patient. This may not apply to patients with severe resting arterial hypoxemia in whom the mechanisms modulating pulmonary gas exchange during exercise have not yet been addressed. What remains to be elucidated at the present time? (a) Which is (are) the precise biochemical mediator(s) of this low pulmonary vascular tone and, presumably, failure of hypoxic pulmonary vasoconstriction? It might be either a substance(s) that the failing liver fails to produce or detoxify. Thus, the ultimate biochemical basis of these physiological abnormalities must still necessarily remain speculative while awaiting future studies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185301 TI - Surveillance for quality assessment: III. The critical assessment of quality indicators. AB - Increased attention to healthcare quality issues by insurers, the public and providers has created the desire for quantitative indicators of high quality care. Attributes of quality indicators, including primary and secondary definitions, predictive accuracy and potential to define avoidable problems in care, have been discussed in an effort to allow the reader to critique suggested quality indicators as they appear through legislation and the literature. A continuous feedback process between reviewers and reviewees in the quality assessment process is mandatory to optimize the performance of quality indicators. PMID- 2185302 TI - Oxazepam: update 1989. AB - Oxazepam is an anxiolytic with established clinical efficacy. Compared to other benzodiazepines it may offer advantages in some patient populations, such as the elderly. Oxazepam has not been associated with more or different risks than other benzodiazepines, and there is no evidence that physiological dependence occurs more frequently with oxazepam than other benzodiazepines. Available evidence suggests that oxazepam may be associated with a lower risk of seizure-induction than lorazepam and alprazolam, and that compared to diazepam, oxazepam may have lower abuse potential. PMID- 2185303 TI - Pooling two controlled comparisons of milnacipran (F2207) and amitriptyline in endogenous inpatients. A new approach in dose ranging studies. AB - Milnacipran is a new potential antidepressant selected for its equipotent inhibition of noradrenaline and serotonin uptake and its lack of effect at any postsynaptic receptor. We recently compared milnacipran 100 and 50 mg/d and amitriptyline 150 mg/d in three parallel randomized groups of major depressive inpatients and found a statistically significant superiority of milnacipran 100 mg/d and amitriptyline over milnacipran 50 mg/d after 4 weeks of treatment. Later on we found similar improvement with milnacipran 200 mg and amitriptyline 150 mg but better tolerance with milnacipran. In order to compare the therapeutic activity of the three doses of milnacipran (50 mg/d, 100 mg/d, and 200 mg/d) we used the responses to amitriptyline as a reference against which to compare the 3 doses of the new drug using analysis of variance on the adjusted data. This approach reveals milnacipran 200 mg is more effective than milnacipran 50 and 100 mg and is the only dose which shows efficacy at least equivalent to that of amitriptyline 150 mg. The dose/efficacy relationship was linear. PMID- 2185304 TI - A genetic sexing system to improve the sterile insect technique against the Mediterranean fruit fly. AB - The autosomal recessive allele v wing (v) in the Mediterranean fruit fly, Ceratitis capitata (Wiedemann), produces flies that when reared at 30 degrees C have stubby wings. The mutant was used to construct a translocation-based genetic sexing system in an attempt to improve the efficiency and effectiveness of the sterile insect release method for field control. PMID- 2185305 TI - Genetic mapping of the Adh locus in the repleta group of Drosophila by in situ hybridization. AB - A biotinylated probe of the Adh (alcohol dehydrogenase) gene of Drosophila melanogaster was used for in situ hybridization on polytene chromosomes of D. mojavensis and D. buzzatii, two species of the repleta group of the genus Drosophila. Hybridization showed that the Adh gene maps at the G1a band of the third chromosome. This is in accordance with a previous result obtained through the use of interspecific hybrid asynapsis as a cytological marker and establishes the limits of the precision of this method. PMID- 2185306 TI - PHYLO: a cluster analysis program. PMID- 2185307 TI - From the museum. PMID- 2185308 TI - Use of pressure support ventilation. PMID- 2185309 TI - Clinical experience with ciprofloxacin: analysis of a multicenter study. AB - In a multicenter study of 132 patients treated with ciprofloxacin for a variety of infections, 35 were microbiologically proven. Of these, bacteriologic cure equaled 85.7%, while improvement equaled 11.4%; failure was 2.9%. Clinical cure equaled 65.8%, while improvement was 26.3%. Failure was reported for 7.9% of cases. A total of 46 (35.9%) infections were classified as chronic. Overall, six of the 132 patients had adverse reactions. Two were related definitely to ciprofloxacin therapy. Therapy with ciprofloxacin was discontinued in two (1.5%) patients because of adverse effects. PMID- 2185310 TI - Immunoelectron microscopy of tissues processed by rapid freezing and freeze substitution fixation without chemical fixatives: application to catalase in rat liver hepatocytes. AB - We report on the immunohistochemical demonstration of an enzyme at the electron microscopic level using specimens processed by rapid freezing and the freeze substitution technique without the use of any chemical fixatives. Fresh rat liver tissue blocks were rapidly frozen by the metal contact method using liquid nitrogen, and were freeze-substituted with acetone without any chemical fixatives at -80 degrees C. Some of the freeze-substituted tissues were embedded in Lowicryl K4M at -20 degrees C; the others were returned to room temperature and embedded in Epok 812 at 60 degrees C. Ultra-thin sections were stained using anti peroxisomal catalase antibody by the protein A-gold technique. The ultrastructure of the hepatocytes was very well preserved compared with that of conventionally processed tissues. The labeling for catalase was confined to peroxisomes. When the labeling density was compared among freeze-substituted tissues and conventionally processed tissues, that of freeze-substituted and Lowicryl K4M embedded tissues was the most intense. These results show the usefulness of freeze-substituted tissues for immunohistochemical analysis of cell organelles. PMID- 2185311 TI - DNA synthesis in excised tobacco leaves after bromodeoxyuridine incorporation: immunohistochemical detection in semi-thin spurr sections. AB - We describe a method for localizing replicating cells in detached tobacco leaves allowed to root. The proposed protocol has shown that formalin fixation and Spurr embedding of petiole bases can be used for demonstrating DNA synthesis after bromodeoxyuridine (BrdU) incorporation. The incorporated BrdU was immunologically visualized. After resin removal, different procedures of DNA denaturation and protease digestion were tested. Combined hydrolysis with 4 N HCl for 10 min at room temperature and digestion with 0.4% pepsin for 15 min at 37 degrees C led to the best reproducible results, with either the peroxidase or the gold detection system. The method is rapid and sensitive, with precise resolution. It can be used at the light and electron microscopic levels. Its potential application is to elucidate in the same organ the role of cytokinins, a class of plant growth regulators, in dividing cells and to define the chronology of their biosynthesis in roots in relation to DNA synthesis. PMID- 2185312 TI - Alcohol abuse-related mesangial glomerulonephritis: immunoelectron microscopy. AB - Immunoelectron microscopy, using post-embedding immunohistochemistry with colloidal gold, was performed on renal samples from forensic autopsies. We confirmed that electron-dense deposits seen in alcohol abuse-related mesangial nephritis correspond to immunoglobulins, as has been shown previously by others in idiopathic cases. We investigated seven control samples and 13 specimens from individuals with evidence of alcohol abuse, six of whom had mesangial nephritis with IgA deposition. We found concentration of the gold particles over large electron-dense deposits in four of six cases of mesangial nephritis, confirming that they correspond to the IgA shown by immunofluorescence. Furthermore, a similar concentration of gold particles was not observed in control cases or in alcoholics without mesangial glomerulonephritis (4/6 vs 0/14; p = 0.005). IgM, seen as small aggregates, was confirmed in only two of six of the same cases. This is the first time that immunoelectron microscopy is performed on tissues obtained post mortem. PMID- 2185313 TI - Neuronal tracing with DiI: decalcification, cryosectioning, and photoconversion for light and electron microscopic analysis. AB - The molecule 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) is a fluorescent dye which diffuses within cell membranes. The properties of DiI diffusion and fluorescence are maintained in aldehyde-fixed tissue, thereby allowing selective neuronal tracing post mortem. We describe three modifications of this tracing method. First, while DiL diffuses along neuronal membranes the tissue can be decalcified in EDTA at 37 degrees C. Tracing in decalcified tissue extends the possible application of the DiI technique to the investigation of neuronal tissue enclosed in bony structures. Second, we describe a protocol that allows sectioning of DiI-injected tissue on a cryostat with minimal subsequent spread of DiI in dried sections. Third, we demonstrate that DiI label of fluorescent neurons in cryosections as well as Vibratome sections can be photo-oxidated and converted to a stable diaminobenzidine reaction product. The photo-converted DiI label is electron dense and allows analysis of labeled cell bodies and processes at the electron microscopic level. DiI does not stay confined to the surface cell membrane in fixed tissue but reaches internal organelles, presumably via membranes of the endoplasmic reticulum, and concentrates in microsomal structures adjacent to mitochondria. Photoconversion of DiI label is compatible with gold immunocytochemistry. Long-term incubation and subsequent photoconversion of post-mortem DiI-labeled neurons provides remarkable tissue preservation at the ultrastructural level. PMID- 2185314 TI - Granulocyte-macrophage colony-stimulating factor stimulates human monocyte accessory cell function. AB - We investigated the effect of recombinant human granulocyte-macrophage CSF (rhGM CSF) on the accessory cell function of purified human monocytes. Compared with untreated monocytes, rhGM-CSF-treated monocytes promoted enhanced mitogen- and Ag stimulated lymphocyte proliferation. This enhancement was significantly inhibited by mAb to rhGM-CSF. In experiments designed to define the mechanism of rhGM-CSF augmentation of accessory cell function, rhGM-CSF was shown to cause a dose dependent increase in monocyte expression of surface HLA-DR molecules and stimulated secretion of IL-1, both important in monocyte T cell interactions. Further studies demonstrated that levels of HLA-DR and IL-1 mRNA were increased by rhGM-CSF, indicating transcriptional regulation of gene expression for HLA-DR and IL-1. Thus, rhGM-CSF augments accessory cell function by human monocytes, and this augmentation correlates with rhGM-CSF-induced increases in transcription of the HLA-DR and IL-1 genes leading to increased expression of surface HLA-DR and secretion of IL-1. PMID- 2185315 TI - Isolation and characterization of circulating immune complexes from rats with experimental membranous nephropathy. AB - Circulating immune complexes (CIC) were isolated from serum from controls and rats with active Heymann nephritis (n = 31) by two methods. CIC detected by the fluid phase Clq binding assay were precipitated from serum using Clq and polyethylene glycol. CIC were also isolated by sequential chromatography with anion exchange and lectin affinity supports. The isolated material was analyzed by PAGE and immunoblotting. The immune complex material isolated by both methods from rats with Heymann nephritis contained the same 60/65-kDa tubular Ag. By immunoblotting, the 60/65-kDa tubular Ag-bound antibodies from rats with active Heymann nephritis, but not antibodies to gp330. Antibody bound to the 60/65-kDa tubular protein in the CIC was isolated. This antibody bound to a similar Ag in glomerular eluates from rats with active Heymann nephritis when tested by immunoblotting. These observations suggest that glomerular immune deposits and CIC in rats with Heymann nephritis contain the same tubular Ag. The 60/65-kDa Ag was isolated from CIC by HPLC using anion exchange and hydrophobic interaction columns. Rats immunized with this Ag developed Heymann nephritis. These studies suggest that CIC contribute to the development of glomerular subepithelial immune deposits in this model of membranous nephropathy. These studies do not exclude the participation of other Ag-antibody systems in Heymann nephritis, including gp330. This report describes methods for isolation and characterization of Ag antibody components of CIC that might be useful to studies of other immune complex-mediated diseases. PMID- 2185316 TI - C3-cleaving membrane proteinase. A new complement regulatory protein of human melanoma cells. AB - Human melanoma cells resistant to killing by the R24 mAb and human complement rapidly degrade surface-deposited C3b (M. Panneerselvam, S. Welt, L. J. Old, C. W. Vogel. 1986. J. Immunol. 136:2534). We report that C-resistant melanoma cells express a membrane proteinase that can cleave C3b, generating a cleavage product with a molecular mass of approximately 30 kDa. The C3-cleaving proteinase was identified on the melanoma cells by its cross-reaction with antiserum to p57, a C3-cleaving proteinase previously isolated from human E membranes (C. Charriaut Marlangue, M. Barel, R. Frade. 1986. Biochem. Biophys. Res. Commun. 140:1113). Preincubation of the C-resistant melanoma cells with anti-p57 IgG or their F(ab')2 fragments increased their susceptibility to complement killing from 25% to approximately 50% and reduced the rate of C3b cleavage and the amount of the 30-kDa fragment generated on the cells. Anti-p57 IgG stained C-resistant melanoma cells by indirect immunofluorescence and precipitated a protein with an apparent molecular mass of 65 kDa. This membrane protein, termed p65, was not detectable on C-susceptible melanoma cells. Membrane extracts from C-resistant melanoma cells also showed C3-cleaving activity when incubated with purified C3 or C3b, similarly generating a C3 fragment of approximately 35 kDa. This fluid-phase C3 cleaving activity could be partially inhibited by anti-p57 IgG. These data suggest that p65 is a C3-cleaving proteinase, antigenically related to p57, that is expressed on C-resistant melanoma cells and responsible for the C resistance of these cells. We propose that the membrane-bound C3-cleaving proteinase represents another C regulatory protein protecting host cells against killing by C. PMID- 2185317 TI - Trypanosomal immunosuppressive factor: a secretion product(s) of Trypanosoma cruzi that inhibits proliferation and IL-2 receptor expression by activated human peripheral blood mononuclear cells. AB - Coculture of blood forms of Trypanosoma cruzi with human PMBC suppresses the expression of several molecules involved in lymphocyte activation, including receptors for IL-2. Our work was initially undertaken to establish whether this effect required physical parasite-PBMC contact or was mediated by a T. cruzi secretion product. Using culture inserts with cell-impermeable membranes, we were able to demonstrate significant suppression of PHA-induced lymphoproliferation whether the trypanosomes were placed in the same compartment as, or separated from, the PBMC. Similar effects were observed by using supernatants from T. cruzi suspensions. These supernatants, which we refer to as trypanosomal immunosuppressive factor, also inhibited IL-2R expression in response to PHA stimulation. The suppressive effect of the secretion product(s) of T. cruzi was reversible, as evidenced by significant recovery of the proliferative capacity of PBMC after removal of the parasite-containing inserts. Moreover, the extent of the suppression produced by trypanosomal immunosuppressive factor subsided as culture time increased. Treatment of trypanosomal immunosuppressive factor with proteases abrogated its suppressive activity, suggesting that the relevant principle(s) was of protein nature. From ultrafiltration experiments, the molecular mass of the suppressive molecule(s) was estimated to be between 30,000 and 100,000 Da. These results demonstrate for the first time the capacity of T. cruzi to spontaneously secrete a factor that suppresses human lymphocyte responses in vitro. This factor, which may play a role in the down-regulation of host immune function observed in acute chagasic patients, might be a useful tool in exploring the mechanisms that regulate the expression of IL-2R and other surface molecules playing key roles in lymphocyte activation. PMID- 2185318 TI - Antibody-dependent killing of Schistosoma mansoni schistosomula in vitro by starch-elicited murine macrophages. Critical role of the cell surface integrin Mac-1 in killing mediated by the anti-Mr 16,000 mAb B3A. AB - Starch-elicited murine peritoneal macrophages were able to kill schistosomula in vitro in the presence of a variety of immune sera. Dose response experiments revealed the superior "quality" of serum from mice vaccinated four times with highly irradiated cercariae (4xVMS) in mediating killing at titers comparable to the other sera tested. B3A, a partially protective mAb (IgG3) that recognizes a Mr 16,000 schistosomular surface Ag, mediated higher levels of killing than any of the sera at comparable titers. In contrast, H12, a partially protective mAb (IgG2a; anti-Mr 32,000), and C1C9, a nonprotective McAb (IgG3; anti-Mr 38,000) failed to mediate killing. Two anti-Mac-1 alpha-chain mAb (5C6 and M1/70) mediated substantial dose-dependent blocking of 4xVMS and B3A-mediated macrophage killing. In contrast, a mAb to the Mac-1-associated beta-chain was less effective, whereas the mAb F4/80 did not significantly block killing despite being present on this macrophage population. Although whole 5C6 Ig was the most efficient at inhibiting B3A-mediated killing, 5C6 Fab fragments were still effective at concentrations as low as 0.5 microgram/ml (10 nM). On a molar basis 5C6 appeared to be more effective at blocking 4xVMS-mediated killing than M1/70, while only M1/70 was capable of inhibiting macrophage adherence to schistosomula. These findings, together with the observation that anti-alpha chain mAb were far more effective at blocking killing than the anti-beta-chain mAb, rules out the possibility that 5C6 is nonspecifically inhibiting B3A-FcR interaction. The data also imply a functional relationship between Mac-1 and FcRIII, the receptor for B3A, in macrophage killing. PMID- 2185319 TI - Immunodiagnosis of bancroftian filariasis. AB - The indirect fluorescent antibody test, the enzyme-linked immuno sorbent assay and the indirect haemagglutination test were evaluated in immunodiagnosis of bancroftian filariasis using W. bancrofti microfilarial antigens. The tests gave a higher positive reactions with microfilaraemic, clinical filarial and endemic normal sera respectively. Non-specific cross-reactions were common in the three tests, so immunodiagnosis should be preceded by stool examination. IFAT gave the highest sensitivity and specificity, while IHAT was the least one. ELISA is simple, sensitive and can be used in seroepidemiological studies. PMID- 2185320 TI - A survey for enteroparasites in Menoufia governorate, Egypt with special reference to Strongyloides stercoralis. AB - The prevalence of Strongyloides stercoralis and other enteroparasites was studied in Menoufia Governorate. 565 stool & 500 serum samples were examined by direct smear, zinc sulphate, stool culture & IFAT using ultrasonicated non digested non fixed filariform larva as antigen. IFAT proved superior than the direct methods since it detected 11.1% of cases while the latter detected only up to 3.4%. The prevalence of enteroparasites was found to be 62.3%. E. histolytica and A. lumbricoides showed the highest incidence while Taenia showed the lowest incidence. PMID- 2185321 TI - [Clinical effects of pulsatile LH-RH administration on ovulation induction for women with various type of amenorrhea]. AB - Using pulsatile LH-RH administration, ovulation induction was performed in women with pituitary dwarfism (PD, n = 1), isolated gonadotropin deficiency (IGD, n = 5), secondary hypothalamic amenorrhea (gestagen negative (AM2, n = 10), positive (AM1, n = 5)), polycystic ovarian disease (PCO, n = 6) and anovulatory cycle (ANOV, n = 1). Five to 20 micrograms of LH-RH was administered subcutaneously with a pulse frequency of 90 min to 2 h, in 76 treatment cycles. The ovulation rate of IGD, AM2, AM1 and PCO was 54.5, 83.3, 12.5 and 50.0%, respectively, all being significantly different from each other. In some cases, ovulation induction was repeated for several cycles without any interruption, and chronic effects of this therapy on the subsequent cycle were examined. In IGD and AM2, subsequent cycles were well stimulated, while those of PCO became refractory. These results indicate that pulsatile LH-RH administration should be the first choice of ovulation induction in IGD and AM2, and less effective in AM1 and PD. When this treatment is applied for PCO, the luteal phase should be supported by alternative methods to avoid pituitary desensitization. PMID- 2185322 TI - [Chlamydia trachomatis infection in a newborn infant delivered by cesarean section]. PMID- 2185323 TI - [Uterine leiomyoblastoma: report of 2 cases]. PMID- 2185324 TI - [Prevention and drug therapy of penicillin resistant gram-negative rod bacterial infections]. PMID- 2185325 TI - [Treatment of diabetes mellitus]. PMID- 2185326 TI - Journey to Jefferson ... continued. PMID- 2185327 TI - Prevention of sudden cardiac death: lessons from the cardiac arrhythmia suppression trial (CAST). PMID- 2185328 TI - Starvation decreases insulin secretion, prostaglandin E2 production and phospholipase A2 activity in rat pancreatic islets. AB - Pancreatic islets, isolated from rats starved for 48 h, secreted significantly less insulin in the presence of 2 mmol glucose/l than islets of fed controls. In contrast, the insulin secretory response of islets from fed and starved rats to a challenge of 20 mmol glucose/l was similar. Concentrations of prostaglandin E2 (PGE2) in islets from starved rats incubated with 2 mmol glucose/l were significantly lower compared with those in control islets obtained from fed animals. Although glucose (20 mmol/l) stimulated PGE2 production in islets from starved and fed rats by 2.7- and 1.6-fold respectively, the concentrations achieved were the same as a consequence of the different prestimulated concentrations. Incubation with [14C]arachidonic acid of sonicated islet preparations from fed rats and separation of metabolites generated by high pressure liquid chromatography, indicated the biosynthesis of a number of cyclo oxygenase- and lipoxygenase-derived compounds, including 6-keto-PGF1 alpha, PGF2 alpha, PGE2 and 12-hydroxyeicosatetraenoic acid. Metabolism of arachidonic acid to cyclo-oxygenase-derived compounds occurred with the same efficiency, but production of lipoxygenase-derived compounds was reduced by 50% in sonicated islets from starved compared with fed rats. Activity of phospholipase A2 of islets from starved rats was significantly less than that measured in islets from fed rats, although the degree of stimulation by 20 mmol glucose/l was the same in both types of islet. These alterations in the phospholipase A2/arachidonic acid cascade may contribute to the diminished insulin secretory response of islets from starved rats to relatively low concentrations of glucose. PMID- 2185329 TI - Gamma/delta T cell clones and natural killer cell clones mediate distinct patterns of non-major histocompatibility complex-restricted cytolysis. AB - Non-MHC-restricted killer cells are cytotoxic lymphocytes that can mediate cytolysis of most tumor targets without apparent selectivity and restriction by the MHC, particularly when activated with IL-2. These effector cells include predominantly NK cells and T cells expressing the TCR-gamma/delta. We found that TCR-gamma/delta-1+, delta TSC1-, BB3+, Ti gamma A+ T cell clones mediate a characteristic cytolytic pattern of non-MHC-restricted cytolysis that is markedly different from NK clones and alpha/beta T cell clones derived from the peripheral blood of the same normal individuals. The characteristic finding is that all BB3/Ti gamma A+ gamma/delta clones mediate strong cytolysis of Daudi cells but they do not lyse Raji cells. In contrast, NK clones from the same donors mediate strong cytolysis of both Daudi and Raji targets. Cytotoxicity by the gamma/delta clones on certain target cells such as Daudi and Molt 4 can be specifically inhibited by mAbs reactive against the TCR-gamma/delta. Therefore, the TCR gamma/delta on these clones either directly recognizes target epitopes on some tumor targets or it is involved in the regulation of their cytotoxic function. The expression of TCR-gamma/delta products reacting with the BB3 and Ti gamma A mAbs reflects the usage of identical TCR-gamma/delta V region genes that appear to be associated with the characteristic pattern of non-MHC-restricted cytotoxicity displayed by this major subset of human peripheral blood gamma/delta cells. PMID- 2185330 TI - Evidence for extrathymic changes in the T cell receptor gamma/delta repertoire. AB - The germline repertoire of variable genes for the TCR-gamma/delta is limited. This, together with the availability of several V delta-specific and a C delta specific mAbs, has made it possible to assess differences in the TCR-gamma/delta repertoire in man. TCR-gamma/delta cells expressing particular V gene segments have been previously shown to be localized in different anatomical sites. In this study, analysis of TCR-gamma/delta V gene segment usage performed on subjects from the time of birth through adulthood revealed striking age-related changes in the TCR-gamma/delta repertoire in peripheral blood. V delta 1+ gamma/delta T cells predominated in thymus as well as in peripheral blood at birth and then persisted as a relatively constant proportion of CD3+ PBL. However, V delta 2+ gamma/delta T cells that constitute a small proportion of the CD3+ cells in thymus and in peripheral blood at birth, then expand and account for the major population of gamma/delta T cells in PBL in adults. No parallel postnatal expansion of V delta 2+ cells in the thymus was observed, even when paired thymus peripheral blood specimens were obtained on subjects between the ages of 3 d and 8 yr. The subset of V delta 2+ lymphocytes that was expanded in peripheral blood expressed high levels of CD45RO suggesting prior activation of these cells, consistent with the possibility that their expansion might have resulted from exposure to foreign antigens or superantigens. In contrast, V delta 1+ T cells in PBL showed no comparable increase in relative numbers and were either negative or expressed only low levels of CD45RO. Consistent with evidence for extrathymic peripheral expansion of selective TCR-gamma/delta subsets, no link between MHC haplotype and differences in the TCR-gamma/delta V gene usage between individuals was apparent, and identical twins displayed TCR-gamma/delta variable gene segment phenotypes that were strikingly different from one another. The elements that determine the TCR-gamma/delta repertoire in individuals are not known. It is possible that both thymic selection and extrathymic factors may influence the peripheral repertoire. Recently, TCR-gamma/delta+ lymphocytes have been shown to expand markedly in peripheral lymphoid tissues and infectious lesions in response to mycobacterial antigens, and a correlation between mycobacterial responses and TCR-gamma/delta V gene usage has been shown in mice. The data presented here demonstrated peripheral age-related changes in the gamma/delta repertoire and point to the importance of extrathymic expansion of specific gamma/delta subsets in generating the human TCR-gamma/delta repertoire. PMID- 2185331 TI - Antibody activity in ankylosing spondylitis sera to two sites on HLA B27.1 at the MHC groove region (within sequence 65-85), and to a Klebsiella pneumoniae nitrogenase reductase peptide (within sequence 181-199). AB - 74 overlapping peptides of varying lengths from Klebsiella pneumoniae nitrogenase reductase (residues 181-199) and from the HLA B27.1 molecule (residues 65-85) were synthesized and tested by ELISA against sera from HLA B27+ ankylosing spondylitis (AS) patients, and sera from HLA B27+ and HLA B27- healthy first degree relatives. Antibody activity in AS sera to Klebsiella peptides of four to eight amino acids was maximal with the peptide NSRQTDR. Activity to HLA B27 peptides was maximal with the peptide KAKAQTDR (named epitope I). These peptides overlap with, but are proximal to the NH2 terminus from QTDRED, which is homologous in HLA B27.1 and K. pneumoniae nitrogenase reductase. A second weaker reactive site was noted in the HLA B27.1 peptides, proximal to the COOH terminus from the homologous sequence, namely peptide REDLRTLL (named epitope II). Little activity was seen against peptides that included the entire homologous sequence. Sera from 50 AS patients showed higher total Ig activity against peptides KAKAQTDR (p less than 0.001) and NSRQTDR (p less than 0.02) than did sera from 22 B27+ and 22 B27- healthy controls. These data indicate that AS patient sera contain antibodies that bind to K. pneumoniae nitrogenase peptides and HLA B27.1 peptides, and that there are at least two epitopes on HLA B27.1 in the alpha 1 domain, at the MHC groove region, that are autoantigenic in AS patients. Epitope I may be a site for crossreactivity between HLA B27 and Klebsiella. PMID- 2185332 TI - The distinct leukocyte integrins of mouse spleen dendritic cells as identified with new hamster monoclonal antibodies. AB - Hybridoma fusions with hamster hosts were undertaken to generate mAbs to mouse spleen dendritic cells. Two mAb were obtained and used to uncover the distinct integrins of these APC. One, 2E6, bound a determinant common to all members of the CD11/CD18 family, most likely the shared 90 kD CD18 beta chain. 2E6 immunoprecipitated the characteristic beta 2 integrin heterodimers from lymphocytes (p180, 90; CD11a) and macrophages (p170,90; CD11b), but from dendritic cells, a p150,90 (presumably CD11c) integrin was the predominant species. 2E6 inhibited the binding function of the CD11a and CD11b integrins on B cells and macrophages in appropriate assays, but 2E6 exerted little or no inhibition on the clustering of dendritic cells to T cells early in primary MLR, suggesting a CD11/CD18-independent mechanism for this binding. The second mAb, N418, precipitated a 150, 90 kD heterodimer that shared the 2E6 CD18 epitope. This N418 epitope may be the murine homologue of the previously characterized human CD11c molecule, but the epitope was only detected on dendritic cells. N418 did not react with peritoneal macrophages, anti-Ig-induced spleen B blasts, or bulk lymph node cells. When used to stain sections of spleen, N418 stained dendritic cells in the T-dependent areas, much like anti-class II mAbs that were also generated in these fusions. In addition, N418 revealed nests of dendritic cells that punctuated the rim of marginal zone macrophages between red and white pulp. This localization positioned most dendritic cells at regions where arterial vessels and T cells enter the white pulp. We conclude that the p150, 90 heterodimer is the major beta 2 integrin of spleen dendritic cells, and we speculate that it may function to localize these APC at sites that permit access to the recirculating pool of resting T cells. PMID- 2185334 TI - Interleukin 3 perfusion prevents death due to acute anemia induced by monoclonal antierythrocyte autoantibody. AB - We have evaluated the therapeutic activity of rIL-3, in comparison with recombinant granulocyte-macrophage CSF (rGM-CSF) and recombinant erythropoietin (rEpo), on a lethal form of acute anemia induced by a single injection of a monoclonal IgG1 anti-mouse RBC (MRBC) autoantibody. Continuous perfusion of rIL-3 before the administration of anti-MRBC mAb prevented animals from the death due to anemia with a rapid recovery in greater than 90% of the cases, while only partial protection (one third of the cases) was obtained by rEpo perfusion, and no protection by rGM-CSF. Since the anti-MRBC mAb induced a marked agglutination of RBC in spleens and livers, and subsequent hemodynamic failure may be an additional contributing factor to the animals' death, the activation of Fc gamma receptor-dependent phagocytosis by rIL-3, as well as the increased number of monocytes/macrophages resulting from rIL-3 perfusion, may also facilitate rapid elimination of these agglutinated RBC, resulting in the further amelioration of the animals' survival. Our results suggest that the therapeutic effect of rIL-3 on anti-MRBC autoantibody-induced anemia is achieved by: (a) its activity to promote the growth and differentiation of erythroid progenitors responsive to Epo and of monocyte/macrophage lineage; and (b) its activity to enhance the phagocytic activity of macrophages to efficiently eliminate agglutinated RBC in spleens and livers. PMID- 2185333 TI - Neutrophil-activating properties of the melanoma growth-stimulatory activity. AB - Melanoma growth-stimulatory activity (MGSA), a peptide reported to be mitogenic for Hs294T human melanoma cells, has extensive sequence similarity to the neutrophil-activating peptide NAP-1/IL-8, suggesting functional similarities. To test this hypothesis, MGSA was chemically synthesized and tested for its effects on human neutrophils. It was found to induce chemotaxis, exocytosis of elastase, and changes in cytosolic-free calcium to an extent and at concentrations similar to NAP-1/IL-8. However, MGSA was considerably less potent than NAP-1/IL-8 in inducing the respiratory burst. Intradermal injections in rats of MGSA resulted in a massive accumulation of neutrophils. Our data demonstrate that, apart from its growth-stimulatory activity, MGSA is a potent inflammatory agonist with neutrophil-stimulating properties. PMID- 2185335 TI - A randomized study of cancer screening in a family practice setting using a recall model. AB - A randomized controlled study that evaluated a recall system and patient education material by mail in 178 asymptomatic female family practice patients aged 50 to 69 years showed no effect on the proportion of patients who had cancer screening tests (P = .20) and a significant adverse effect on the mean number of tests performed (P = .05) after 4 months. In a subgroup of previous compliers (those who had one or more tests 12 months before the study), however, there was a lower proportion of patients receiving one or more tests (P = .019) with a lower mean number of tests (P = .007) than previous compliers in the control group. Recall strategies for cancer screening tests need to be more extensively studied in the United States before they are routinely adopted in family practice. PMID- 2185336 TI - Pseudocyesis. PMID- 2185337 TI - Recombinant human granulocyte-macrophage colony-stimulating factor reduces hematologic toxicity and widens clinical applicability of high-dose cyclophosphamide treatment in breast cancer and non-Hodgkin's lymphoma. AB - High-dose administration of anticancer agents is attractive both on theoretic and clinical grounds. Yet, high-dose regimens are usually used as salvage treatments, mainly as a consequence of their considerable hematologic toxicity. One pertinent example is represented by cyclophosphamide, an alkylating agent with a wide spectrum of marked antitumor activity. When used at doses up to 7 g/m2 (190 to 200 mg/kg) this drug does not cause myeloablation, but induces a severe, albeit transient, myelosuppression, which requires platelet transfusions in approximately 50% of treated patients, and is frequently complicated by infectious episodes, occasionally lethal. To accelerate hematopoietic recovery, we continuously infused for 14 consecutive days 5.5 micrograms/kg/d of the glycosylated human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) into 15 patients with breast cancer and non-Hodgkin's lymphoma treated with 7 g/m2 cyclophosphamide. This schedule was chosen having obtained the fastest hematopoietic recovery among four different options during an initial schedule-finding phase on 12 overall patients. Twenty-one comparable subjects with solid tumors served as controls. We report here that this relatively low, well-tolerated dose of rhGM-CSF reduces from 20 to 14 (median) and from 24 to 14, the number of days required to recover circulating granulocyte counts over 1,000 and 2,500/microL, respectively. The stimulatory effect was associated with a remarkable clinical benefit. In fact, treated patients experienced less infectious complications (7% v 24%) were eligible to receive chemotherapy earlier (median, by day +14 v day +20 for controls), and fewer required prophylactic platelet transfusions (13% v 43%). Our results show that even very high doses of cyclophosphamide can be administered with improved hematologic toxicity, tolerable morbidity, and reduced supportive care requirements. The increase in the therapeutic index made possible by rhGM-CSF infusion prompts the use of high dose cyclophosphamide, and possibly of other agents with similar myelotoxic activity, early in the clinical course of chemotherapy-sensitive tumors. PMID- 2185338 TI - Allogeneic bone marrow transplantation in adults with Burkitt's lymphoma or acute lymphoblastic leukemia in first complete remission. AB - The prognosis of adults with Burkitt's lymphoma is very poor and depends on initial CNS and/or bone marrow involvement. We report results in nine adult patients with CNS (n = 9) and/or bone marrow involvement (n = 7) treated in first complete remission (CR) with allogeneic bone marrow transplantation (BMT). CNS treatment before the conditioning regimen consisted of cranial irradiation at 15 Gy (n = 8) and intrathecal chemotherapy (n = 9). The conditioning regimen included cyclophosphamide and total body irradiation (TBI) in a single dose. No postgraft CNS prophylaxis was administered. At the present time, seven patients are alive and disease-free at 18, 23, 44, 47, 54, 54, and 59 months. Two patients died at 14 and 7 months from transfusion-related acquired immune deficiency syndrome and bacterial septicemia and were disease-free at the time of their death. These preliminary results should encourage the use of BMT. A prospective randomized trial is warranted to further specify and investigate the advantages of allogeneic BMT versus conventional chemotherapy. PMID- 2185339 TI - Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia. AB - The National Cancer Institute (NCI) sponsored a workshop to develop a set of standardized diagnostic and response criteria for acute myeloid leukemia (AML) clinical trials. The French-American-British (FAB) classification was retained for diagnosing AML, with the addition of patients with bone marrow morphologic features of a myelodysplastic syndrome and less than 30% bone marrow blasts, but with greater than or equal to 30% blasts in the peripheral blood. In this report, there are four important subgroups of AML not defined in the FAB classification that are discussed: undifferentiated acute leukemia, MO (AML lacking definitive myeloid differentiation by morphology or conventional cytochemistry but with ultrastructural or immunophenotypic evidence for AML), mixed lineage leukemia, and hypocellular AML. Definitions of response for clinical trials are presented to facilitate comparisons among different studies. Complete remission is considered the only response worth reporting in phase III trials, since lesser responses do not improve survival. Partial remissions may be of interest to identify active new agents in phase I and II studies. Monoclonal antibodies and cytogenetic studies are not part of the routine assessment of remission or reassessment at relapse, and their role in the evaluation of patients with AML is currently being evaluated in clinical trials. Although we recognize that some of the definitions in this report are arbitrary, generalized use of these guidelines will make results of clinical trials more comparable and interpretable. PMID- 2185340 TI - Efficacy of adjuvant chemotherapy for patients with resectable head and neck cancer: a subset analysis of the Head and Neck Contracts Program. AB - To evaluate the efficacy of adjuvant chemotherapy for patients with advanced head and neck squamous cancer, the Head and Neck Contracts Program conducted a three arm study comparing standard surgery and radiation, induction chemotherapy (cisplatin and bleomycin) plus standard therapy, and induction chemotherapy plus standard therapy followed by maintenance cisplatin for 6 months. As previously reported, this trial of 462 patients demonstrated no significant difference in disease-free survival or survival, but a significantly lower metastatic rate in the maintenance arm. To determine whether particular subgroups may have benefited from adjuvant therapy, we evaluated results based on primary site, and tumor (T) and node (N) stage. Of the 192 patients with oral cavity cancer, those on the maintenance arm had a significantly improved 3-year disease-free survival (67%) compared with the standard arm (49%) or induction arm (44%) (overall P = .05). For hypopharyngeal and laryngeal cancers there was no marked overall benefit. For the 106 patients with T1 plus T2 disease, there was marginal improvement in disease-free survival for the maintenance group (72%) compared with the standard group (47%) or induction group (43%) (overall P = .09). There was no advantage for patients with T3 and T4 disease. There was superior disease-free survival for patients with N1 disease on the maintenance arm (70%) compared with the standard arm (42%) (P = .024). The same was true for disease-free survival in 109 patients with N2 disease: standard (52%), induction (30%), maintenance (84%) (overall P less than .001). There was no benefit for N3 disease. A significant survival advantage with maintenance chemotherapy was only seen for N2 disease (overall P = .04). Since head and neck cancer patients are a heterogeneous group, there may be particular sites and stages for which adjuvant chemotherapy would be advantageous, and subset analysis can help indicate directions for new trials. PMID- 2185341 TI - Aromatase inhibition with 4-hydroxyandrostenedione in the treatment of postmenopausal patients with advanced breast cancer: a phase II study. AB - Estrogen deprivation by aromatase inhibition is an effective treatment in breast cancer. Between October 1986 and March 1988, 91 postmenopausal patients with advanced breast cancer entered a phase II study performed jointly in three center to investigate the new aromatase inhibitor 4-hydroxyandrostenedione. Patients received 500 mg 4-hydroxyandrostenedione intramuscularly (IM) every 2 weeks for 6 weeks, and 250 mg every 2 weeks thereafter. There were two complete (CRs) and 19 partial remissions (PRs) (response rate, 23%). Disease stabilization (no change; NC) was seen in 26 patients, and in 44 patients (48%), disease progression occurred. Duration of the CRs is 20+ months, median durations of PR and NC are 13+ and 8 months, respectively. Receptor status, relapse-free interval, and sites of metastatic lesions did not appear to influence treatment results. However, efficacy of previous tamoxifen treatment favorably predicted response to 4 hydroxyandrostenedione. Serum estradiol levels decreased significantly in patients after 2 weeks of treatment. Side effects were mostly nonspecific and of low degree, requiring discontinuation of treatment in only 3% of the patients. We conclude that aromatase inhibition with 4-hydroxyandrostenedione is efficacious in the treatment of postmenopausal breast cancer. PMID- 2185342 TI - Concomitant chemoradiotherapy: rationale and clinical experience in patients with solid tumors. AB - Concomitant chemoradiotherapy can be used in order to increase both the local and systemic control of solid tumors. The rationale for its use and experimental data for selected chemotherapy drugs are reviewed. Clinical trials have focused on increasing complete response (CR) and survival rates; in addition, improved quality of life by decreasing the use of conventional surgical procedures is being pursued. Both of these goals may have been achieved for some tumors, most notably for anal cell carcinoma. Improved survival with concomitant chemoradiotherapy has also been shown for patients treated on randomized studies for pancreatic, colorectal, small-cell lung, head and neck, and cervical cancer. These results call for the continued investigation of this approach in the laboratory and in the clinic. PMID- 2185343 TI - The new International Neuroblastoma Staging System: some critical notes. PMID- 2185344 TI - Comparison of the efficiency of three methods for the determination of staphylococcal beta-lactamase. AB - Three methods for demonstrating the production of beta-lactamase in resistant strains of Staphylococcus aureus were compared. The "satellite phenomenon" method proved to be more sensitive than the nitrocefin test and the iodometric test. PMID- 2185345 TI - Current strategies to reduce cisplatin toxicity. PMID- 2185346 TI - Screening for asymptomatic gonorrhea in males: a comparison of four techniques. AB - A total of 729 asymptomatic men were screened for gonococcal urethritis with four techniques: culture of urethral specimens, culture of first-catch urine sediment (FCUS), an enzyme immunoassay method (Gonozyme, Abbot Laboratories) for detection of gonococcal antigen in urethral specimens (EIA-Sb) and first-catch urine sediment (EIA-FCUS). The positivity rates of the aforementioned techniques were 0.13%, 0%, 2.33%, and 0.82%. In view of reduction of time and patients' discomfort as well as the closely comparable positivity rate (p less than 0.05) associated with the use of the EIA-FCUS technique, the latter method appears to be the simplest, most practical and reliable diagnostic tool for screening asymptomatic gonococcal urethritis. PMID- 2185347 TI - The effect of antimycotics on secretory acid proteinase of Candida albicans. AB - The effect of antimycotics on secretory aspartate (acid) proteinase, a virulence enzyme of Candida albicans, was investigated. The conditions of the study were such as to induce proteinase production in the stationary phase of growth (25-40 hours), when no antifungal tested, except the polyene derivative methyl partricin, significantly reduced the viability of the culture. Among azole derivatives, fenticonazole (FZ) but not miconazole, fluconazole or ketoconazole, exerted strong inhibition on proteinase, in typical dose-diphasic pattern, (0.01 microgram/ml; 1-10 micrograms/ml). 5-fluorocytosine (5-FC) was also inhibitory at a dose interval 1-10 micrograms/ml. In all cases, the inhibition concerned the synthesis of the enzyme rather that its activity as suggested by the results of comparative ELISA, SDS-PAGE and spectrophotometric methods of proteinase detection. Finally, the inhibition of proteinase production by FZ and 5-FC mainly reflected the effect of these antimycotics on general protein synthesis. PMID- 2185348 TI - Immunological characterization and localization of the Na+/Ca2(+)-exchanger in bovine retina. AB - The sodium/calcium exchanger was purified from bovine retinal rod outer segment membranes and used for the immunization of New Zealand White rabbits. A polyclonal antibody was produced which was found to bind specifically to the 230 kDa Na+/Ca2(+)-exchanger protein as assessed by Western blotting. The antibody did not bind to the high-molecular-weight "rim protein," thereby demonstrating that this protein is distinct from the rod outer segment of Na+/Ca2(+)-exchanger. We used the polyclonal antibody for immunohistochemically localizing the exchange protein in bovine retina. Fluorescent light microscopy revealed intensive immunolabeling of the photoreceptor outer segments, whereas other retinal cell layers exhibited minimal binding. Using the electron microscopic immunogold method, we found specific antibody binding to the extracellular side of rod outer segment plasma membrane. Rod disk membranes, rod inner segments, and cone photoreceptors displayed no significant labeling. We therefore conclude that the Na+/Ca2(+)-exchanger is localized primarily in the rod outer segment plasma membrane, the most appropriate localization considering its proposed role in the process of vertebrate phototransduction. PMID- 2185349 TI - Predicted reductions in the risk of coronary heart disease by antihypertensive therapy: the confounding effect of lipids. AB - The treatment of arterial hypertension confers several important benefits, e.g. reducing hypertension-induced cardiovascular morbidity and mortality. However, the preventive effect for coronary heart disease is considerably smaller than the effect of treatment on the incidence of strokes. Several factors may explain this discrepancy, but it appears likely that drug-induced increases in serum lipoproteins may, to some extent, offset the risk reduction obtained through the lowering of blood pressure. It appears that more emphasis should be put on therapeutic intervention in other risk factors in addition to the treatment of hypertension. An appropriate therapeutic aim of the treatment of hypertension should be to lower blood pressure to 'normotensive' levels, by using drugs which do not themselves increase cardiovascular risks, e.g. do not increase serum lipoproteins, and to actively intervene against other co-existing risk factors, such as hyperlipidaemia. By using this approach, it seems likely that the risk of coronary heart disease can be reduced. PMID- 2185350 TI - Clinical trials for the reduction of coronary artery disease: a critical review. AB - Our present knowledge about risk factors and cardiovascular events has a solid foundation in epidemiological studies. However, if it is clear that the link between risk factors and events is represented by the pathogenetic role that hypertension, hypercholesterolaemia and cigarette-smoking have in arterial atherosclerotic disease, we still do not know whether these risk factors contribute to the progression from silent atherosclerosis to atherosclerotic events. This may explain some of the difficulties we have in interpreting the results of primary prevention trials. The anatomical regression of atherosclerotic plaques obtained by treating risk factors could be the clue to a better understanding of the clinical phenomena. PMID- 2185351 TI - Lipoprotein receptors: therapeutic implications. AB - Knowledge of the transport pathways for cholesterol in blood helps us to understand the mechanisms underlying genetic and acquired forms of hypercholesterolaemia, and sets the stage for rational treatment with diet and drugs. A key element is a cell-surface receptor that binds cholesterol-rich lipoproteins of intermediate and low density. Genetic defects in this low-density lipoprotein receptor cause familial hypercholesterolaemia, an autosomal-dominant disease that affects 1 in 500 persons. An acquired deficiency in this receptor can be produced by diets that are rich in cholesterol and saturated fatty acids. This suppression may play a role in diet-induced hypercholesterolaemia. PMID- 2185352 TI - Natural history of hypertension and kidney disease in diabetes. AB - Diabetic nephropathy is the most severe complication of insulin-dependent diabetes mellitus. Epidemiological studies have shown that 30-40% of the patients develop this complication, which is associated with an increase in mortality. Haemodynamic factors, in particular, hyperfiltration, increased flow, and capillary hypertension have been suggested to be of pathogenetic importance, but this is still controversial. Of clinical importance is the close association between clinical diabetic nephropathy and increased blood pressure. Several studies have demonstrated a beneficial effect of early antihypertensive therapy. Most encouraging, however, is the recent finding of a reduced mortality in patients with diabetic nephropathy in whom early antihypertensive therapy has been carried out. PMID- 2185353 TI - The roles of angiotensin II and prostaglandins in the regulation of the glomerular filtration of albumin. AB - Angiotensin (Ang) II and prostaglandins, especially prostaglandins E2 and I2, regulate the glomerular filtration of albumin. Albuminuria can be induced by angiotensin II and possibly by prostaglandins. Angiotensin converting enzyme inhibition with captopril, enalapril or lisinopril reduces albuminuria and glomerular injury in experimental and clinical renal diseases, especially diabetes mellitus. Inhibition of prostaglandin synthesis with non-steroidal anti inflammatory drugs reduces albuminuria in nephrotic patients regardless of the aetiology of the nephrosis. Judicious clinical use of either class of therapy can result in sustained reductions (50-75%) in proteinuria and possible attenuation of the rate of decline of glomerular function. PMID- 2185354 TI - Diabetic nephropathy in normotensive patients. AB - Arterial pressure is within 'normal' limits in most diabetic patients with or without microalbuminuria and elevated in 70% of patients with overt diabetic nephropathy. An abnormal increase in the level of urinary excretion is a strong predictor of the subsequent development of overt diabetic nephropathy and ultimately renal insufficiency. Correction of hypertension is associated with a reduction in the rate of decline of the glomerular filtration rate in overt diabetic nephropathy. In patients with microalbuminuria, short-term studies have shown that angiotensin converting enzyme (ACE) inhibitors, in contrast with calcium antagonists, decrease urinary albumin excretion. Additional studies assessing the long-term effect of antihypertensive agents on the evolution of early diabetic nephropathy are needed. The superiority of ACE inhibitors over other antihypertensive agents in the treatment of overt or early diabetic nephropathy remains to be demonstrated. In addition to arterial pressure control, it is possible that optimal glycaemic control in addition to the modification of protein intake, dietary sodium and serum lipid profile may alter the course of diabetic nephropathy. PMID- 2185355 TI - Potentiometric determination of captopril. AB - A rapid, accurate and reproducible method for the potentiometric determination of captopril in aqueous solution, is described. The method is based on the reaction of the thiol and the carboxylic group of captopril with silver ions whereby an equivalent amount of the acid is liberated; thereafter, the amount of captopril is determined by the potentiometric titration with sodium hydroxide. This method can be applied also for direct determination of captopril content in tablets. PMID- 2185356 TI - [Artificial blood: the future of blood transfusion? I. Hemoglobin solutions]. AB - To palliate certain drawbacks in blood transfusion, some preparations are studied as oxygen-transporting erythrocytic substitutes; these are preparations of a biological origin such as hemoglobin solutions, or synthetic preparations such as fluorocarbon emulsions. Part 1 studies solutions of purified, pyridoxylated and/or polymerized hemoglobin of human or animal origin. PMID- 2185357 TI - [New antimalarial sustained-release formulations based on bioresorbable polymers: therapeutic evaluation using the Plasmodium berghei model]. AB - Chemotherapy keeps an important place in malaria control programme. The development of schizonticidal formulations, which may maintain their efficacy for at least one month after single administration, becomes needful. These formulations should allow to assure a suitable patient compliance and to avoid the disadvantages of high plasmatic peaks. The aim of this study is to evaluate the therapeutic efficacy of implantable bioresorbable reservoir-forms. The use of these polymers allow to avoid the surgical extraction of implanted preparations. Two drug delivery systems were prepared: microspheres and rods. Pyrimethamine, as a drug model was incorporated. Therapeutic activity of these preparations was evaluated on a TB mice-Plasmodium berghei model. Polycaprolactone and polylactide 100 microspheres are not suitable for long-term treatment. In contrast, implantable subdermic rods allowed to fulfil the long-term coverage requirements. Their activity depend on the administered dose and the drug content in implants. Polycaprolactone, polylactide 100 and polylactide 50 implants containing respectively 21.5%, 19-40% of pyrimethamine have protected animals for at least three months. PMID- 2185358 TI - Kaposi's sarcoma of the lower extremity as the first sign of AIDS. AB - The authors review four cases of Kaposi's sarcoma that were presented to the Foot Clinics of New York and affiliated North General Hospital during a 1-year period from the fall of 1987 to the fall of 1988. The authors conclude that it is sometimes difficult to diagnose Kaposi's sarcoma and to differentiate between the acquired immunodeficiency (AIDS) form and the classic form. Guidelines for diagnosis and a profile of the AIDS-related and non-AIDS-related Kaposi's sarcoma patient are discussed. PMID- 2185359 TI - Pin tract infections. Incidence and management in foot surgery. AB - The development of pin tract reactions and their sequelae is based on a complex series of events. Analysis of pin tract infections directly related to static external wire fixation at Kern Hospital for Special Surgery from 1981 through 1988 showed an incidence of 0.46%; however, the overall incidence is probably higher. A discussion of the pathogenesis and guidelines for prevention, diagnosis, and treatment are presented. The authors suggest that pin tract infections occur because of postoperative skin contamination, rather than intraoperative implantation. PMID- 2185360 TI - Osteonecrosis in patients receiving dialysis: report of two cases and review of the literature. AB - Two patients receiving maintenance dialysis therapy developed osteonecrosis, the first in the humeral head and the second in the talus. Both patients lacked known risk factors for developing osteonecrosis. A possible pathogenic role of secondary hyperparathyroidism in this disorder is suggested. Rheumatologists evaluating patients receiving maintenance dialysis with rheumatic manifestations should be aware of this potential complication. PMID- 2185361 TI - Localized peripheral calcium oxalate crystal deposition caused by Aspergillus niger infection. AB - A 70-year-old white man, who was malnourished and demented, presented with a painful black, gangrenous-appearing right foot with a fungating mass and required amputation. Pathological sections of the tissue specimens showed numerous birefringent crystals, which were identified as calcium oxalate. Branching septate hyphae and darkly pigmented fungal fruiting heads with double sterigmata characteristic of Aspergillus niger were also identified in the tissue sections. No systemic or other metabolic causes of oxalosis were found. The calcium oxalate crystal deposition was felt to be secondary to Aspergillus niger infection. PMID- 2185362 TI - A review of current concepts on the pathogenesis of juvenile rheumatoid arthritis. PMID- 2185363 TI - Malaria sporozoite detection by dissection and ELISA to assess infectivity of afrotropical Anopheles (Diptera: Culicidae). AB - Malaria infection rates determined by dissection and Plasmodium falciparum enzyme linked immunosorbent assay (ELISA) were compared for 26,935 Anopheles gambiae Giles sensu lato and 17,739 Anopheles funestus Giles collected during 20 mo in western Kenya. ELISA infection rates were about 43% higher than dissection sporozoite rates. In dissection-negative Anopheles, circumsporozoite (CS) protein was detected by ELISA in 5.2% of 10,017 salivary gland samples and in 12.2% of 237 thorax samples. The accuracy of dissection and ELISA techniques was compared by the following tests on a group of 352 field-collected Anopheles (held 10 d to ensure sporogonic development): salivary gland dissection, examination of Giemsa stained dissection slides, ELISA tests on salivary gland and thorax body parts, and microscopic techniques for determining sporozoite loads. Respective infection rates were 9.9%, 10.8%, and 15.6% for dissection, stained slides, and ELISA. Sporozoite loads were associated significantly with ELISA absorbance values (r = 0.76). Compared with Giemsa-stained dissection slide results, the sensitivity of sporozoite detection was 92.1% for dissection compared with 78.9% for ELISA; specificity was 100.0% for dissection versus 92.0% for ELISA. Immunological detection of CS protein in head-thorax samples of Afrotropical vectors overestimated the proportion of infective Anopheles because the comparison of techniques indicated that 45.4% of the ELISA positive Anopheles did not contain salivary gland sporozoites. PMID- 2185364 TI - Fluorescence histochemical techniques for catecholamines as tools in neurobiology. AB - Formaldehyde-induced and glyoxylic-acid-induced fluorescence histochemistry permits the tissue localization of catecholamines in the central nervous system (CNS) and peripheral nervous system (PNS), and in culture. Counterstains such as ethidium bromide provide excellent background identification of specific innervated regions in both the CNS and the periphery. Use of fluorescence histochemistry with immunocytochemistry can elucidate catecholamine-peptide relationships. Gelatin-ink perfusion used with fluorescence histochemistry permits the investigation of neuro-vascular relationships and documentation of vascular and parenchymal compartmentation of innervation. Combined use of fluorescence histochemistry and retrograde tracing methods demonstrates the specific cellular sources of innervation of target regions. Micropunch neurochemical analysis provides quantitative data for correlation with fluorescence histochemistry within a target region of innervation, and microspectrofluorometric analysis provides a semi-quantitative evaluation of the amount of fluorophore within a target region or within specific subcellular compartments such as the cell body or terminals. PMID- 2185365 TI - Positron emission tomography--a new technique for studies of the central nervous system. AB - Positron emission tomography (PET) has become an important tool to study the central nervous system. Examples of such studies are cerebral blood flow and metabolism and determination of receptor characteristics of the brain. In the following the basic principles and the physics behind PET are given. Different aspects are discussed such as detector design, image reconstructions and data analyses. Since quantification is essential in PET, data have to be corrected for absorption, scatter and random coincidences. These corrections and their influence on image data are discussed. A review of state-of-the-art PET research of the brain is given. PMID- 2185366 TI - The bcl-2 gene, follicular lymphoma, and Hodgkin's disease. PMID- 2185367 TI - Involvement of the bcl-2 gene in Hodgkin's disease. AB - A major obstacle to investigations of Hodgkin's disease is the paucity of malignant cells, i.e., Reed-Sternberg cells and their variants, in tissues of patients with this disease. Consequently, the pathogenesis, cell of origin, and clonality of this relatively frequent lymphoma have remained unresolved. Results of recent studies suggest that in some instances Reed-Sternberg cells carry rearranged immunoglobulin heavy-chain joining region (JH) loci as well as chromosomal translocations involving band 14q32. Prompted by these findings, we sought to determine if the t(14;18) (q32;q21) translocation of follicular, non Hodgkin's B-cell lymphoma was associated with Hodgkin's disease. To detect the possible t(14;18) (q32;q21) translocation within the rare malignant cells of Hodgkin's disease, we amplified sequences created by the t(14;18) translocation using the polymerase chain reaction (PCR). With this approach, DNA sequences carrying the direct fusion of the major breakpoint region of the candidate oncogene, bcl-2, derived from chromosome 18q21, with JH on chromosome 14q32 can be detected in as few as one in 10(5)-10(6) cells. In the present study, joined bcl-2/JH sequences were detected in tissues involved by Hodgkin's disease in 17 of 53 (32%) patients. The frequent association of bcl-2 translocation with Hodgkin's disease suggests that this oncogene has a role in the pathogenesis of Hodgkin's disease. That bcl-2 is involved in a major class of lymphoma in addition to follicular lymphoma implies a role for additional factors responsible for generating the two distinctive clinical and pathologic disease states. PMID- 2185368 TI - Creatine kinase: race-gender differences in patients hospitalized for suspected myocardial infarction. AB - Race-gender differences in creatine kinase values were studied in 647 consecutive patients admitted for suspected myocardial infarction. The lowest value in a serial set for each patient was used for group comparisons. Significant differences were found between Hispanic females and black males, using standard values. Using log creatine kinase values, significant differences were found among blacks, Caucasians, and Hispanics. Males had higher log creatine kinase values than females, but no differences were found between sexes within racial groups. Body surface area differences (significant between males and females) did not explain all of the racial-gender differences found. Reexamination of ranges of normality, taking into account race-gender differences, is strongly supported by these data. PMID- 2185369 TI - Health reforms and the black community. PMID- 2185370 TI - Long struggle continues to find new weapons against an old foe--the malaria parasite. PMID- 2185371 TI - A trial of clonidine to stop smoking. PMID- 2185372 TI - Ventilation/perfusion scan in pulmonary embolism. 'The Emperor is incompletely attired'. PMID- 2185373 TI - The doctor in the house diagnoses flux and frustration. PMID- 2185374 TI - [Current aspects of drug therapy of juvenile chronic arthritis]. AB - From the sight of avoiding crippling and dying owing to juvenile chronic arthritis the importance of pharmacologic therapy is discussed. New opinions on the application of medicines already used are elaborated, new medicaments (piroxicam, sulfasalazin) are represented. PMID- 2185375 TI - [Obstructive bronchitis and bronchial asthma: attempt at a status determination]. AB - Despite some similarities and fluent changes of the clinical feature it is proposed to distinguish on principle between bronchiolitis, obstructive bronchitis and asthma. Main reasons for such a practice are: age-related peculiarities of the respiratory system, different aetiology and pathogenesis, variable therapeutic measures and a different prognosis. PMID- 2185376 TI - Mechanism of oncogenesis in retinoblastoma. PMID- 2185377 TI - Effects of antihypertensive agents on blood pressure and the progress of renal failure in partially nephrectomized spontaneously hypertensive rats. AB - The purpose of this study was to investigate the effects of antihypertensive agents on blood pressure and the development of glomerular changes in salt loaded, 5/6 nephrectomized spontaneously hypertensive rats (SHR). Thirty-two spontaneously hypertensive rats with 5/6 nephrectomy were divided into 4 groups: a control group (N = 8), and group treated with 10 mg/kg/day trichlormethiazide. (N = 8), 30 mg/kg/day captopril (N = 8), and 200 mg/kg/day nicardipine (N = 8). Each of these antihypertensive drugs was added to the drinking water for 10 weeks and the rats were given the drugs and a high-salt diet (5% NaCl). During the experiment, body weight and systolic blood pressure were measured every 2 weeks. At the end of the study, blood was collected for determination of serum creatinine, blood urea nitrogen, serum protein, serum sodium and potassium, and plasma renin activity and aldosterone concentration. Also renal tissues were obtained for light and electron microscopic examination at the end of the study. Systolic blood pressure in 5/6 nephrectomized SHR loaded with a high salt was significantly reduced by administration of trichlormethiazide (155 +/- 12 versus 204 +/- 12 mm Hg), but not by administration of either captopril or nicardipine. However, levels of serum creatinine were not significantly elevated in rats treated with captopril and nicardipine (control: 0.93 +/- 0.11 mg/dl, captopril: 0.62 +/- 0.01 mg/dl, nicardipine: 0.55 +/- 0.05 mg/dl). In contrast to changes in blood pressure, marked glomerular sclerosis with hyalinosis, which was found in the control group was not ameliorated by treatment with trichlormethiazide. However, these changes were not observed in rats treated with either captopril or nicardipine in spite of the absence of a prominent fall in blood pressure. These data suggest that captopril and nicardipine ameliorated glomerular injury regardless of the level of systolic blood pressure through the direct and/or indirect actions on the glomerulus. PMID- 2185378 TI - Substrate dependency of neurite outgrowth from adult human chromaffin cells. Inhibitory effects of human brain tissue. AB - Attempts to treat Parkinson's disease with grafts of chromaffin cells to the caudate nucleus have recently generated considerable interest. However, it is not known whether chromaffin cells can innervate the human central nervous system. We have directly addressed this question by measuring neurite outgrowth in cultures of normal adult human chromaffin cells on frozen sections of caudate nucleus and other substrates, a technique previously employed in animal studies. Chromaffin cells from radical nephrectomies were plated on frozen sections of caudate nucleus and heart, and on polylysine-coated slides, and were maintained for up to 3 weeks in medium with nerve growth factor to induce neurite outgrowth and cytosine arabinoside to prevent proliferation of other cell types. Additional cultures maintained for up to 3 weeks in nerve growth factor without tissue sections were trypsinized to remove processes and replated on frozen sections or polylysine to evaluate process regeneration. Processes were quantitated after visualization by glyoxylic acid-induced fluorescence. No more than 14% of cell clusters formed processes longer than 100 microns on caudate nucleus, versus 24% on heart and up to 84% on polylysine (all p less than .01). Comparable patterns were obtained for neurite regeneration. Our findings suggest that human brain tissue is for the most part inhospitable to neurites produced by sympathoadrenal cells, and that even tissues normally innervated by such cells are less hospitable than synthetic substrates. These findings might have important implications for future studies related to chromaffin cell transplantation. PMID- 2185379 TI - LeGrand Guerry, M.D., 1873-1947, President, SCMA, 1908. PMID- 2185380 TI - Ph-chromosome positive acute leukemias and acute phase CML: one or two diseases? Two. PMID- 2185381 TI - Changing response of clonogenic myeloid leukemia blasts to granulocyte-macrophage colony-stimulating factor (GM-CSF) during anti-leukemic therapy--a case report on the basis of a clinical phase II trial. AB - In a clinical phase II trial GM-CSF was applied to 23 patients with acute leukemias carrying a high risk of early death because of old age or advanced disease. Concomitant laboratory investigations included the analysis of colony assays for normal granulopoietic progenitors (CFU-GM) and leukemic CFU-L with and without the addition of GM-CSF, as well as DNA measurements by flow cytometry (FCM) for the detection of DNA-aneuploidies. The present analysis is focused on one particular patient with acute myeloid leukemia (AML) in whom the detection of a DNA aneuploidy provided the readily accessible means to monitor the response of leukemic blasts to induction chemotherapy and subsequent GM-CSF treatment in vivo complementing the colony assay analyses performed in vitro. Prior to therapy 60% of cells revealed a DNA aneuploidy with a DNA index of 1.26 and in-vitro exposure of leukemic bone marrow blasts to GM-CSF (100 U/ml) enhanced the growth of CFU-L and CFU-GM with a significantly higher stimulatory index for CFU-L (1:19 versus 1:5.5). Three days after the completion of two cycles of induction therapy with thioguanine, cytosine arabinoside and daunorubicin (TAD 9) a morphologic bone marrow evaluation revealed aplasia without leukemic blasts. By FCM DNA analysis, however, 8% residual aneuploid cells were found. No growth of CFU-L was observed at this time point neither spontaneously nor after the addition of GM-CSF which induced the growth of CFU-GM, only. In-vivo application of GM-CSF (250 micrograms/mg2/day by continuous 24-h infusion) led to the recovery of normal granulopoiesis without evidence of a concomitant stimulation of aneuploid leukemic cells. These data indicate a change in the susceptibility of leukemic blasts to GM-CSF before and after chemotherapy. A reduction of the leukemic cell burden below a critical level or a selection of GM-CSF non-responsive early leukemic precursor cells may account for these observations. PMID- 2185382 TI - The Mayo brothers and politics. PMID- 2185383 TI - Gastrointestinal laser endoscopy--future horizons. AB - The laser, especially the neodymium:yttrium-aluminum-garnet device, has been a dominant influence on the development of gastrointestinal therapeutic endoscopy. More than 2,000 such procedures were performed in the first 5 years of experience with laser endoscopy at the Mayo Clinic. The major areas for future development are (1) the control of acute and chronic gastrointestinal bleeding, (2) the palliation of malignant gastrointestinal neoplasms, and (3) the management of benign and malignant obstructive lesions of the biliary tract. Refinements in laser devices, delivery systems, and techniques such as photodynamic therapy will be needed to achieve more selective tissue destruction. Improvements in the new adjunctive endoscopic methods of electronic (video) endoscopy and ultrasonography may enhance evolving laser applications by more accurately identifying diseased tissues and guiding their destruction. PMID- 2185384 TI - Professor Julius Tandler, anatomist and public health advocate. PMID- 2185385 TI - Acute myocardial infarction: initial manifestations, management, and prognosis. AB - In patients with suspected acute myocardial infarction (AMI), obtaining a thorough history is important for identifying both the cause of chest pain and any concurrent conditions that may complicate the management. Physical examination--including cardiac auscultation and determining the status of the peripheral vasculature--is important as a guide to immediate management and as a baseline for future comparison. The differential diagnosis of AMI is extensive, and various laboratory tests, such as electrocardiography, cardiac enzymes, radionuclide techniques, echocardiography, and cardiac catheterization, can aid in the diagnosis. The routine management of patients with AMI can include medical therapy with antithrombotic agents, nitrates, beta-adrenergic blockers, or calcium channel blocking agents. The major differences between Q-wave and non-Q wave infarction are discussed. Some factors that affect early and late prognosis in patients with AMI are age of the patient, residual left ventricular function, residual myocardial ischemia, and substrates for sustained ventricular arrhythmias. Although much of the current enthusiasm in management of AMI is related to revascularization strategies, other important aspects of diagnosis and treatment should not be overlooked. PMID- 2185386 TI - Advances in interventional cardiology. AB - The field of interventional cardiology is growing widely. This growth is the result of improvements in existing technology, development of new technology, and expansion of criteria for the selection of patients. Percutaneous transluminal coronary angioplasty (PTCA) remains the mainstay and is used to treat an increasing number of patients with coronary artery disease that manifests as stable or unstable angina or acute myocardial infarction. Atherectomy is being used to "debulk" lesions and remove atheromatous plaque as well as to remove intimal flaps after PTCA. The insertion of an intracoronary stent is a strategy designed to treat intimal dissections and acute closure as well as to attempt to decrease the incidence of restenosis. Finally, intracoronary laser therapy- independently or in combination with PTCA--is being evaluated as a treatment approach for more diffuse disease, acute occlusion, and prevention of restenosis. PMID- 2185387 TI - Management of postoperative pain: review of current techniques and methods. AB - Pain is a common problem in the early postoperative period. Techniques that provide perioperative analgesia to alleviate pain may have a significant effect on postoperative events, such as earlier ambulation and earlier dismissal from the hospital with use of epidural analgesia than with systemic analgesia. Spinal opioids, which can be administered epidurally or intrathecally, provide analgesia that is superior to that achieved with systemically administered narcotics. For procedures on the upper extremities, selective analgesia can be achieved with use of various types of neural blockade--for example, brachial plexus blockade, interscalene blockade, and axillary plexus blockade. Intercostal nerve block, a valuable but underutilized procedure appropriate for unilateral upper abdominal or flank operations or for thoracotomy, has been shown to reduce postoperative narcotic requirements and pulmonary complications. A patient-controlled analgesia device, consisting of an electronically controlled infusion pump with a timing device that can be triggered by the patient for intravenous administration of a narcotic when pain is experienced, avoids the vast fluctuations in analgesia that accompany parenteral administration of drugs. In most patients, postoperative pain can be prevented or diminished, and clinicians should be aware of the available techniques for achieving this goal. PMID- 2185388 TI - [Disorders of esophageal function as a cause of thoracic pain]. AB - Oesophageal disorders can be identified in about one third of the patients with non cardiac chest pain. Motility disturbances and gastro-oesophageal reflux are the leading causes of chest pain of oesophageal origin. Heart diseases and organic lesions of the oesophagus have to be ruled out by cardiological examination and endoscopy, respectively. Oesophageal motility testing and long term-pH-metry are useful to further characterize the underlying functional disorder. Because of the spontaneous fluctuations of symptoms and the effects of placebo treatment therapy should be conservative and based on the results of these investigational procedures. PMID- 2185389 TI - Immunoreactive endothelin concentrations in maternal and fetal blood. AB - Immunoreactive-endothelin (ir-ET) concentrations were determined in peripheral maternal blood and in umbilical cord blood just after delivery. The concentrations in both the umbilical artery (2.83 +/- 1.36 pmol/l plasma, Mean +/ SD) and vein (3.37 +/- 1.53 pmol/l) were significantly higher than those found in maternal venous blood (1.43 +/- 1.02 pmol/l). On the other hand, ir-ET levels in maternal blood were not significantly different when compared with those found in non-pregnant women (1.50 +/- 0.83 pmol/l). No significant difference of ir-ET levels between the umbilical artery and vein was observed. A highly significant correlation (r = 0.60, p less than 0.01) of ir-ET levels between the umbilical artery and vein was observed. Also, a significant correlation (r = 0.48, p less than 0.01) between umbilical vein and maternal vein ir-ET levels with a weaker correlation (r = 0.36, p less than 0.05) between umbilical artery and maternal vein ir-ET levels was demonstrated. The present study indicates that ir-ET may be actively secreted in fetal circulation and the plasma levels in maternal and fetal circulation may have a possible relation. PMID- 2185390 TI - Prenatal diagnosis: historical and futuristic perspectives. AB - Prenatal diagnosis is a rapidly expanding field, as the latest advances in human genetics continue to embrace the newer technologies in gynecology and obstetrics. PMID- 2185391 TI - Pneumocystis carinii pneumonia: diagnosis and management. AB - As management of HIV infection becomes more proactive, early identification of persons at risk for PCP and initiation of preventive therapy will become more routine, and the clinical impact of P. carinii may be ameliorated. PMID- 2185392 TI - Reynaldo L. Lee-Llacer MD 1990-1991, Med Chi President. PMID- 2185393 TI - Estimates of public costs for teenage childbearing in Baltimore City in FY 1987. AB - In 1987 Baltimore City spent about $179,500,000 on AFDC, Medicaid, and food stamps for families that were begun when the mother was a teenager. Had all these births been delayed until the mother was at least 20 years old, Baltimore would have saved almost $72,000,000 in public outlays. PMID- 2185394 TI - Case report and review of literature: hypernatremia in breast-fed infants. PMID- 2185395 TI - Adjuvant therapy in melanoma. Part I: Background, chemotherapy, radiation, and nonspecific immunotherapy. PMID- 2185396 TI - Virulence plasmids of Salmonella typhimurium and other salmonellae. AB - Related high molecular weight plasmids of several serotypes and species of Salmonella have been associated with virulence in a variety of animal models of infection. The primary virulence plasmid phenotype is in the ability of salmonellae to spread beyond the initial site of infection, the intestines. The mechanism of this plasmid-mediated invasive infection has not been identified, but may be a complex interaction in the host-pathogen relationship. A common region of the salmonella plasmids has been associated with virulence, and specific virulence genes and their products are now being identified; however, much is yet to be accomplished in this field. The combined analysis of pathogenesis and genetics associated with the salmonella virulence plasmids may identify new systems of bacterial virulence and the genetic basis for this virulence. PMID- 2185397 TI - Cloning and nucleotide sequencing of Vero toxin 2 variant genes from Escherichia coli O91:H21 isolated from a patient with the hemolytic uremic syndrome. AB - Cellular DNA extracted from Escherichia coli strain B2F1 (O91:H21) was found to contain two separate DNA sequences that hybridized with a Vero toxin 2 (VT2) specific gene probe under stringent conditions. These two sequences were cloned and both were shown to encode a variant of Vero toxin 2 (VT2vh). The nucleotide sequences of the operons encoding VT2vh, designated as vtx2ha and vtx2hb, were determined. The two operons were nearly identical (99% overall DNA homology) and both encoded A subunits of 319 amino acid residues and B subunits of 89 amino acid residues, the A and B subunit genes being separated by a stretch of 14 bp. The A and B subunit genes of the vtx2ha operon exhibited 98.6% and 95.5% DNA homology, respectively, with those of the slt-II operon encoding Shiga-like toxin II (or VT2) cloned from a strain from a patient with hemorrhagic colitis, while the A and B subunit genes of the vtx2ha operon showed 94.5% and 82.8% DNA homology, respectively, with those of the slt-IIv operon encoding a SLT-II variant cloned from a strain isolated from a pig with edema disease. The nucleotide sequences of the presumed promoters and presumptive ribosome binding sites in the vtx2ha, vtx2hb, and slt-II, and slt-IIv operons were identical. These results indicate that nucleotide sequences encoding a family of VT2-related toxins are present in various strains of E. coli and that the sequences of the genes for A subunits are better conserved than those of the B subunit genes. PMID- 2185398 TI - Treatment of established osteoporosis and rehabilitation: current practice and possibilities. PMID- 2185399 TI - The choice of antimicrobial drugs. PMID- 2185401 TI - [Endothelium-dependent modulation of circulation and thrombocyte function by endothelium-derived relaxing factor, an "endogenous nitro-vasodilator"]. PMID- 2185400 TI - Fluconazole. PMID- 2185402 TI - [Atherosclerosis and endothelium-derived relaxing factor]. PMID- 2185403 TI - [Inhibition of platelet aggregation by endothelium-derived relaxing factor-like agents]. AB - In the last years, an inhibition of aggregation by organic nitrates or by similar drugs has been demonstrated by some authors, but has also been ruled out by other authors. The present work was thus performed to study a possible inhibition of platelet aggregation by the respective drugs in comparison with the molecular mechanism of action of these drugs, that is activation of soluble guanylate cyclase. We found that in vitro, organic nitrates activate soluble guanylate cyclase and inhibit platelet aggregation only in millimolar concentrations, while sodium nitroprusside and SIN-1, the active metabolite of molsidomine, influence these parameters in micromolar concentrations. This difference between the actions of the O-NO2-containing nitrates and the NO-containing compounds nitroprusside and SIN-1 is, however, not apparent ex vivo. Ex vivo, not only molsidomine, that is converted in the liver to SIN-1, but also isosorbide-5 mononitrate inhibited platelet aggregation. Thus, it appears that organic nitrates can in vivo release nitric oxide in a tissue other than platelets in amounts that are high enough to inhibit platelet aggregation. These studies suggest, that an antiaggregatory effect may participate in the clinical actions not only of drugs that directly resemble EDRF, such as SIN-1, but also by the organic nitrates. However, since nitrates cannot be activated directly by the platelets, it appears that also the antiaggregatory effects of nitrates, but not of molsidomine, underlie the mechanisms of tolerance development. PMID- 2185404 TI - [Acute and chronic effects of molsidomine in therapeutic coronary angioplasty]. AB - The effects of the molsidomine metabolite SIN-I (0.5 mg) on tolerance to ischemia were studied in twelve patients during coronary angioplasty of the LAD. SIN-I resulted in a significant prolongation of time to ST-segment alteration one, five and ten minutes after intracoronary injection. Beside hemodynamic reasons the effects of SIN-I on circulating blood cells and collateral perfusion are discussed as mechanisms of action. The effects of molsidomine (2 X 8 mg/d) on restenosis rate after initially successful coronary angioplasty were studied in 393 patients in a prospective, randomized and controlled trial. 29% of patients treated with molsidomine experienced restenosis at control coronary angiography at six months. The control group receiving nifedipine (3 X 20 mg/d) and acetylsalicylic acid (1 X 500 mg/d) showed a restenosis in 33% of patients. Therefore, molsidomine seems as effective as nifedipine and acetylsalicylic acid in treating patients after coronary angioplasty. PMID- 2185405 TI - [Significance of endothelium-derived relaxing factor for the pathophysiologic understanding of coronary heart disease]. PMID- 2185406 TI - [Nutrition problems in adolescents]. PMID- 2185407 TI - [Adolescents, violence and the law]. PMID- 2185408 TI - [Adolescents, aggression, mass media violence]. PMID- 2185409 TI - [Violence in adolescence. Sudden and provoked violence]. PMID- 2185410 TI - [Violence and sexual violence in adolescents]. PMID- 2185411 TI - [The adolescent and the newborn. Sensitization to parenthood]. PMID- 2185412 TI - [Physiologic aspects of adolescents]. PMID- 2185413 TI - [Sociologic aspects of adolescents]. PMID- 2185414 TI - [Non-sexual functions of adolescent sex]. PMID- 2185415 TI - [Menstrual disorders in adolescence]. PMID- 2185416 TI - Dose-effects functions for carboxyhemoglobin and behavior. AB - Literature on dose-effects functions of carboxyhemoglobin (COHb) and human behavior is internally inconsistent. A recent study was performed to describe such a function for tracking behavior in humans (7). No significant effects were found, however, even for COHb levels up to ca. 17%. The present review and analysis of published data was undertaken to attempt to reduce uncertainty about COHb dose-effects functions. Dose-effects data from six laboratory animal operant behavior studies were reviewed. Maximum COHb levels ranged from 33 to 59%. Data were converted to a common metric and dose-effects functions were fitted. The preferred function was nonlinear, with a shallow slope, indicating small effects (if any) for COHb levels less than ca. 20%. As COHb increased further, the slope of the function became progressively steeper. Review of the human dose-effects function publications for COHb and behavior revealed that no significant findings had survived the test of direct or partial replication. Other studies found no significant effects. A dose-effects curve was fitted to the human data from one study (7) and compared to the laboratory animal curves. Extrapolation of the human curve was used to suggest that the dose-effects curves for humans and laboratory animals were of similar form and that effects of COHb on behavior in man are small or absent below ca. 20%. It is also possible that some uncontrolled variables are affecting the results so that COHb produces effects only some of the time. No conclusion can be drawn from the body of literature due to the divergence of results. PMID- 2185417 TI - [Natural transformation in bacteria]. AB - Transformants may be formed by some bacterial species when the growing cultures are mixed. This phenomenon caused by the DNA release from bacterial cells is called natural transformation. DNA release is most likely to be mediated by cell autolysis. Both chromosomal markers and plasmids are transferred by natural transformation. The phenomenon is reproduced while growing bacteria together in sterile soil. The DNA adsorbed on sand and other soil solid particles was more resistant to DNAse action, than the free transforming DNA. Natural transformation seems to be one of the forms of the genetic exchange in bacteria in their habitats. An indirect argument for this suggestion is perfect coordination between the different steps of transformation process, at least, in some bacterial species. PMID- 2185418 TI - [The effect of Ha-ras oncogene on cells immortalized by the gene for polyomavirus large T-antigen]. AB - Activated human Ha-ras oncogene cloned on the plasmid pEJras6,6 was transfected into REF (LT) cells immortalized by the gene for large T-antigen of the polyoma virus. The cells were shown to become completely transformed (in the terms of morphology and tumorogeneity) only after three cycles of transfection with the plasmid pEJras6,6. The integrated sequences of the plasmid pEJras6,6 and the ras oncogene product p21Ha-ras were detected in cells only after their selection in the nude mice (in the cell culture REF (LT) ras X 3tu obtained from the tumor and directly in the tumor cells). Thus, after sequential transfections with a c-Ha ras oncogene we developed cell cultures on the different stages of transformation process. PMID- 2185419 TI - [Construction and analysis of the tularemia pathogen gene library in Escherichia coli]. AB - The library of tularemia causative agent genes cloned on the pHC79 plasmid and the partial clonotek of these agents genes in Escherichia coli cells have been constructed. The immunochemical analysis has revealed seven clones of Escherichia coli harbouring the recombinant plasmids and expressing francisella antigens. The cloned sequences of francisella DNA as well as the recombinant plasmids containing them and coding for francisella antigens are capable of specific hybridization with the DNA from Francisella tularensis strains and Francisella novicida strain U112. The cloned DNA sequences have the properties of the genetic radiospecific molecular DNA probe. PMID- 2185420 TI - [Expression of Photobacterium leiognathi bioluminescence system genes in Escherichia coli]. AB - Expression of Photobacterium leiognathi bioluminescence genes under the control of lac, tac, tet promoters in Escherichia coli cells has been studied. The position of the genes for aliphatic aldehyde biosynthesis and for the synthesis of luciferase subunits was identified. The plasmid pBRPL1 has been constructed containing the system of bioluminescence genes devoid of promoter following the polylinker DNA fragment. The plasmid can be used for selection of promoter containing DNA sequences as well as for studying the promoters regulation in process of Escherichia coli cells growth. PMID- 2185421 TI - [The effect of proteolytic cleavage of potato virus X coat protein on its ability to self-assemble with RNA and viral infectivity]. AB - The process of proteolytic cleavage of potato virus X coat protein molecules inside the virions and in the dissociated state in the course of their purification and storage has been studied. In agreement with the previous reports, the intact form (Ps) of the coat protein in the viral particles was found to be gradually cleaved to three discrete lower molecular forms (Pi, Pf, Pu). During the storage of the dissociated coat protein preparations further cleavage was observed with formation of at least three additional lower molecular weight forms (Ppa, Ppb, Ppc). The location of proteolytic cleavage sites leading to formation of Ppa form was determined. The shortened forms Pi, Pf, Pu and Ppa (and possibly Ppc) were found to be incorporated into the viral particles in the course of reconstitution in vitro with the viral RNA. Infectivity of the virus containing only intact (Ps) form of the protein was found to be two to three folds higher than that of the virus containing only Pf form of the coat protein. PMID- 2185422 TI - Genotoxicity of benzo[a]pyrene, 2-nitrofluorene and airborne particulates in the DNA-repair host-mediated assay. AB - The genotoxic activity of benzo[a]pyrene (BAP), 2-nitrofluorene (NF) and airborne particulate matter was evaluated in the DNA-repair host-mediated assay after intraperitoneal or intratracheal administration. Dimethylnitrosamine (DMNA), used as a positive control, showed a genotoxic effect after both intraperitoneal and intratracheal administration, the strongest effect being found in liver, followed by lungs and kidneys, whereas a weak effect was observed in the spleen. In general no difference in genotoxicity was found between the 2 administration routes used. For BAP, although clearly positive in vitro, a moderate dose dependent effect was found only in the liver after intraperitoneal administration. NF, which was positive in vitro both with and without a metabolizing system, produced no genotoxic effect in any of the organs tested after intraperitoneal administration. Extracts of airborne particulate matter which were genotoxic in vitro failed to cause a genotoxic effect in vivo by either route of administration. Possible explanations for the differences between the data obtained in vitro and in vivo are discussed. PMID- 2185423 TI - Malaria: the path of drug resistance. PMID- 2185424 TI - Several alleles of the multidrug-resistance gene are closely linked to chloroquine resistance in Plasmodium falciparum. AB - The lethal form of human malaria caused by Plasmodium falciparum is virtually uncontrollable in many areas because of the development of drug resistance, in particular chloroquine resistance (CQR). CQR is biologically similar to the multiple drug resistance phenotype (MDR) of mammalian tumour cells, as both involve expulsion of drug from the cell and both can be reversed by calcium channel antagonists. A homologue (pfmdr1) of the mammalian multidrug resistance gene has been implicated in CQR because it is amplified in some CQR isolates of P. falciparum as is an mdr gene in MDR tumour cells. We show here that the complete sequences of pfmdr1 genes from 2 CQ sensitive (CQS) P. falciparum isolates are identical. In 5 CQR isolates, 1-4 key nucleotide differences resulted in amino acid substitutions. On the basis of these substitutions, we have correctly predicted the CQS/CQR status of a further 34 out of 36 isolates. This is a paradox as CQR arises much less frequently than would be predicted if single point mutations were sufficient. We conclude that a mutated pfmdr1 gene is one of at least two mutated genes required for CQR. PMID- 2185425 TI - Human U2 snRNA can function in pre-mRNA splicing in yeast. AB - The removal of introns from messenger RNA precursors requires five small nuclear RNAs (snRNAs), contained within ribonucleoprotein particles (snRNPs), which complex with the pre-mRNA and other associated factors to form the spliceosome. In both yeast and mammals, the U2 snRNA base pairs with sequences surrounding the site of lariat formation. Binding of U2 snRNP to the highly degenerate branchpoint sequence in mammalian introns is absolutely dependent on an auxiliary protein, U2AF, which recognizes a polypyrimidine stretch adjacent to the 3' splice site. The absence of this sequence motif in yeast introns has strengthened arguments that the two systems are fundamentally different. Deletion analyses of the yeast U2 gene have confirmed that the highly conserved 5' domain is essential, although the adjacent approximately 950 nucleotides can be deleted without any phenotypic consequence. A 3'-terminal domain of approximately 100 nucleotides is also required for wild-type growth rates; the highly conserved terminal loop within this domain (loop IV) may provide specific binding contacts for two U2-specific snRNP proteins. We have replaced the single copy yeast U2 (yU2) gene with human U2 (hU2), expecting that weak or no complementation would provide an assay for cloning additional splicing factors, such as U2AF. We report here that hU2 can complement the yeast deletion with surprising efficiency. The interactions governing spliceosome assembly and intron recognition are thus more conserved than previously suspected. Paradoxically, the conserved loop IV sequence is dispensable in yeast. PMID- 2185426 TI - Stress and silent myocardial ischemia. A new research study at Duke University Medical Center. PMID- 2185427 TI - A classmate's tribute to Dean Wilburt C. Davison. A recently discovered and previously unpublished memorial note by Wilder G. Penfield, M.D. PMID- 2185428 TI - Albert Heyman, M.D. Boundless role model for generations of physicians. PMID- 2185429 TI - The journal interviews state legislative leaders. Interview by Edward C. Halperin. PMID- 2185430 TI - Molecular biology of diazepam binding inhibitor peptide. AB - Complementary DNA (cDNA) clones containing the entire coding sequence for Diazepam Binding Inhibitor (DBI) peptide, a 10-kDa precursor of putative natural ligands of benzodiazepine recognition sites, were isolated from rat, human and cow libraries. The sequence of all these clones is highly conserved; however, the N-terminal sequence predicted by the human DBI clone differed from that of the other two clones. DBI cDNA, utilized as hybridization probe in Southern blot analysis, revealed that DBI of both human and rat might be encoded by a multiple family of 4-6 genes. Furthermore, we have used in situ chromosomes hybridization to map human DBI genes. The results indicate that a human DBI gene is localized on chromosome 2 and that three of the four hybridization signals detected by the human DBI probe are located on three other chromosomes. These findings raise a question as whether multiple DBI genes encode for different molecular forms of DBI. In the attempt to test this hypothesis, cow cDNA and human genomic libraries were screened with DBI cDNA. In this paper I report the isolation of clones from these libraries which, although hybridizing well to DBI cDNA, possess a low percentage of homology (46.7%), randomly distributed within the coding region of DBI cDNA. Whether or not these clones encode for peptides sharing the same physiological role as DBI is under investigation. PMID- 2185432 TI - Jean A. Sicard (1872-1929). His pioneer work in nervous diseases. PMID- 2185433 TI - Intracranial calcified deposits in neurofibromatosis type 2. A CT study of 11 cases. AB - CT examinations of 11 consecutive patients with neurofibromatosis type 2 (NF-2) revealed non-tumoral intracranial calcified deposits in seven cases. Abnormal calcification of the choroid plexus was found in six cases. Calcification in the cerebellar hemispheres was observed in four cases. In two cases nodular calcifications on the surface of the cerebral hemispheres were detected. Our findings and the data in the literature show that non-tumoral calcifications of different locations can be regarded as part of the NF-2 syndrome. PMID- 2185431 TI - GABAergic mechanisms in the electrophysiological actions of ethanol on cerebellar neurons. AB - We have found that the partial inverse benzodiazepine agonists Ro 15-4513 and FG 7142 antagonize the depressant electrophysiological effects of locally applied ethanol in the cerebellum. Although absolute tissue concentrations are not known, dose-response curves constructed using pressure-ejection doses as previously described we found that FG 7142 was more efficacious, but less potent than Ro 15 4513. Our observation that ethanol and inverse benzodiazepine agonists have interactions which are not competitive might suggest that these two drugs act through separate, but interactive mechanisms in order to produce the observed ethanol antagonism. If such independent interactions were mediated at different sites on a given macromolecular complex, such as the GABAa/Cl- channel, then one might expect to find allosteric interactions between those sites as well as with the functional response of the complex to GABA activation. Indeed, this hypothesis is consistent with the recent finding of Harris and collaborators that ethanol potentiates the inverse agonist actions of Ro 15-4513 and FG 7142. On the other hand, we were unable to find large ethanol-induced potentiations of GABA effects on all neurons which showed depressant responses to ethanol administration in rat cerebellum. However we did find that the GABAa antagonist, bicuculline, blocks the depressant effects of ethanol on the same neurons. We conclude that the interaction between ethanol and GABA probably does not occur directly at the GABAa receptor site, but that the GABAa mechanism does play a permissive role in the ethanol-induced depressions of cerebellar Purkinje neurons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185434 TI - Serial imaging of Menkes disease. AB - The patient developed myoclonic seizures at 3 months of age and his hair demonstrated the pili torti pattern. The low serum copper content and ceruloplasmin confirmed the diagnosis of Menkes disease. The characteristic signs on the images were: high echo level regions in the cerebrum as detected by brain ultrasonography, low density areas of white matter detected by CT scan, and low signal intensities of white matter by both T1 and balanced MR images. PMID- 2185435 TI - Colour Doppler imaging of arteriovenous malformation of the vein of Galen in a newborn. AB - We report a neonate with congestive heart failure due to a huge arteriovenous malformation of the vein of Galen. Two dimensional ultrasound showed a large cystic structure behind the 3rd ventricle and the quadrigeminal plate. The cyst compressed the posterior part of the 3rd ventricle and the aqueduct and caused an obstructive hydrocephalus. The diagnosis was established by colour Doppler imaging (CDI). With the help of CDI, flow within the aneurysm could be shown as well as feeding arteries originating from the posterior and middle cerebral arteries. The straight sinus and the torcular Herophili were markedly dilated. PMID- 2185436 TI - The biochemical basis and pathophysiology of status epilepticus. AB - Status epilepticus (SE), both convulsive and nonconvulsive, can arise from diverse etiologies in either a normal brain or a previously epileptic brain. SE has a distinct natural history and unattended can lead to profound, life threatening, systemic metabolic and physiologic disturbances. These factors may account for the poor prognosis associated with this disorder. However, there is mounting experimental evidence that SE itself, independent of metabolic and physiologic disturbances, leads to lasting brain dysfunction. PMID- 2185437 TI - Intellectual impairment as an outcome of status epilepticus. AB - Mental ability changes following status epilepticus (SE) are explored. With respect to the studies reviewed, it is noted that (1) most dealt with children, (2) few utilized any formal psychologic assessment, (3) most were retrospective, (4) earlier studies tended to disclose greater losses in mental ability than later studies, and (5) most investigators described at least a few adverse changes attributable to SE rather than to underlying neurologic disease. An original prospective study is also reported. PMID- 2185438 TI - The pharmacokinetics of agents used to treat status epilepticus. AB - A thorough understanding of the pharmacologic properties of lipid-soluble drugs is essential when using these agents to treat status epilepticus. In addition to physiologic factors, such as blood pressure and cerebral blood flow, pharmacokinetic principles, including half-life, distribution, elimination, and volume of distribution (with special regard to an agent's lipid-solubility rating), should be applied. These factors, in toto, will influence the choice of drug, its loading dose, and its therapeutic dose. PMID- 2185439 TI - Status epilepticus: the next decade. AB - Advances in the treatment of status epilepticus (SE) in the past decade have significantly improved the prognosis for this condition. Although currently available intervention techniques can eliminate mortality attributable to seizures, death associated with SE is usually caused by the disorder that precipitated the SE. Therefore, since currently available drugs for the treatment of SE possess significant shortcomings, new treatment modalities must be developed. PMID- 2185440 TI - Treatment of status epilepticus in children. AB - In children, seizures associated with status epilepticus (SE) include a number of types that are age-related. These types of seizures are not associated with SE in older patients. Likewise, etiologies of SE in children are also unique to this patient population, in particular those responsible for SE in the neonate. Consequently, therapy must address specific treatment of any possible underlying condition in addition to appropriate interventional and supportive measures. PMID- 2185441 TI - Status epilepticus: epidemiologic considerations. AB - Status epilepticus (SE) will occur in 50,000 to 60,000 individuals in the United States annually: one third as the presenting symptom in patients with a 1st unprovoked seizure or with epilepsy, one third in patients with established epilepsy, and one third in individuals with no history of epilepsy. The greatest number of cases will occur in children, although the risk is equally high in the over-60 population. In patients with epilepsy, SE is more likely to occur in those with partial seizures and in those with remote symptomatic epilepsy. The presence of a preexisting neurologic abnormality is associated with an increased risk of SE in those with acute systemic insults. There is a high mortality reported, but this is related predominantly to the underlying condition. The 1 to 2% mortality attributed to SE probably reflects an overestimation of the risk. There is an increased risk of seizures and of intellectual dysfunction following the occurrence of an episode of SE, although the causal association is not clear. Individuals with epilepsy who experience an episode of SE probably have a lower likelihood of remission of epilepsy. PMID- 2185442 TI - Changing concepts of the pathogenesis of diabetic nephropathy. PMID- 2185443 TI - Henry Keller, MD, of New York and the Alyn Hospital in Jerusalem. PMID- 2185444 TI - Root surface caries--an overview of aetiology, prevalence, prevention, and management. AB - Root surface caries is a specific clinical entity which has been receiving increasing attention in recent years. It has a complex, multi-factorial aetiology, but all the causal factors, and their relative contributions, are not yet clear. There appears to be a role for one or more microbiological agents, particularly in association with a diet involving frequent ingestion of fermentable sugars. Gingival recession is almost certainly a pre-requisite for the development of root surface caries, but intra-oral, site-specific differences in prevalence confuse the picture. Figures of between 20 and over 70 percent for gross prevalence have been reported, with demonstrated attack rates of between 15 and 28 percent of susceptible surfaces being affected. Difficulties in diagnosis may limit the reliability of these figures. The prevention of root surface caries is a two-phase process; the initial emphasis is on the prevention of gingival recession, and the later approach involves measures aimed at reducing the frequency of intake of known cariogenic foodstuffs, and increasing the resistance of susceptible root surfaces with topical fluoride. Medicines which can cause dry mouth must also be examined. The treatment of root surface caries involves a range of procedures, from topical fluoride to multi-surface, glass ionomer cement restorations. PMID- 2185445 TI - Human nutrition--paradoxes of drugs and diet. AB - Complex historical and other reasons account for public confusion concerning optimal nutritional practice. The mass media are not alone in presenting results of scientific work in non-scientific form. Health professionals, scientists, and people from industry have all contributed to the confusion concerning diet and the public good. Extrapolation from one situation to another, simplification of issues, and biased presentation of data, have intensified the problems. The limited perspective of many experts is frequently coupled with over-enthusiastic promotion of what are really hypotheses rather than established truths. The public good is not being served by the present confusing pattern of paradoxes. There is an urgent need for health professionals to review their presentations to the public such that emerging scientific knowledge is presented effectively in terms of a broad perspective. PMID- 2185446 TI - Naso-orbital-ethmoid injury: report of a case and review of the literature. AB - Trauma to the midface severe enough to cause nasal fractures will often result in fractures of the bony naso-orbital-ethmoid (NOE) complex. Extensive damage may be encountered in the interorbital area because of the fragility of the bony framework. The medial orbital walls, ethmoid sinuses, and cribriform area of the anterior cranial fossa can resist a maximum compressive force of only 30 g. NOE injuries are usually the result of either a direct blow sustained during an altercation or of a high-velocity motor vehicle accident. Quite often multiple systemic injuries serve to complicate treatment. NOE fractures present the surgeon with numerous challenges during repair. The delicate bony architecture, anatomic framework, and cosmetic expectations indicate comprehensive, thorough treatment. Damage to the eye, which is basically an extension of the brain, is of major concern. Pupillary discrepancies, retrobulbar hematoma, and damage to the optic nerve must be ruled out. Early surgical management is indicated because delayed repair or inadequate treatment prediposes the patient to defects that may be extremely difficult if not impossible to correct with secondary procedures. Numerous articles have been published describing the NOE injury. The multifaceted array of fractures seen in NOE injuries has been formulated into a comprehensive classification by Gruss. PMID- 2185447 TI - Hemophilic pseudotumor of the mandible. Report of a case. AB - Hemophilic pseudotumor of bone is a rarely encountered lesion associated with hemophilia. To date, only eight cases in the mandible have been reported in the literature. A rare case occurring in the mandible of a 2 1/2-year-old child required the fabrication of a customized wound obturator for postoperative wound care after surgical curettage. The literature is reviewed and the obturator described. PMID- 2185448 TI - Patent nasopalatine ducts: four case presentations and review of the literature. AB - Patent nasopalatine ducts are a rare entity, only 12 cases being reported in the English literature. Four new cases are presented, the world literature is reviewed, and possible mechanisms of formation are discussed. PMID- 2185449 TI - Periodontitis and angular alveolar lesions: a critical distinction. AB - Modern anthropologic and epidemiologic studies reveal that the incidence of periodontitis is low in both ancient and modern populations. The distribution of plaque and gingivitis has little or no correlation with the distribution of pathologic alveolar bone loss or with periodontitis. The assumption that a distance from cementoenamel junction to alveolar crest (CEJ-AC distance) greater than 2 mm equates with disease overlooks the interrelationship between the CEJ-AC distance and continuous eruption in compensation for tooth wear and growth of the lower face height. Anatomic, physiologic, and pathologic factors increasing CEJ AC distances are reviewed. Where horizontal periodontitis does result from gingivitis, it is usually of minimal significance and probably occurs when the host defenses have been diminished by environmental factors commonly associated with other chronic diseases. A pulpal-alveolar explanation for localized angular alveolar lesions better fits the clinical features of this form of periodontal bone loss than does the conventional hypothesis of primary periodontal infection by specific oral bacteria. PMID- 2185450 TI - Oral candidiasis and hairy leukoplakia correlate with HIV infection in Tanzania. AB - We report a detailed study on oral lesions and their association with the WHO revised provisional case definition of AIDS as well as serologic signs of HIV infection among 186 patients in Dar Es Salaam, Tanzania. The patient material consisted of 39 hospitalized suspected AIDS patients, 44 medical nonsuspected patients, 53 dental outpatients, and 50 patients with sexually transmitted diseases. The male:female ratio was 2.1:1 on average. Oral examination was done without knowledge of the HIV status of the patients. Among 39 suspected AIDS patients 97% had WHO AIDS criteria and 90% were seropositive for HIV. Among the 147 patients not suspected of having AIDS 18 (12%) had AIDS criteria and 15% had serologic evidence of HIV infection. The presence of WHO AIDS criteria correlated significantly with the presence of HIV antibodies, but not with HIV antigen. Oral lesions were found in 54% of those with AIDS criteria and 52% of HIV-infected patients, as compared to 3% and 6% of the patients without AIDS criteria and HIV infection, respectively (p less than 0.01). Among patients with AIDS atrophic candidiasis occurred in 21%, pseudomembranous candidiasis in 23%, hairy leukoplakia in 36%, herpetic stomatitis in 2%, Kaposi's sarcoma in 4%, and nonspecific ulcer in 4%. The presence of oral lesions had a high predictive value for presence of AIDS criteria as well as for presence of HIV infection in this hospital setting. All patients should have a thorough oral examination and the presence of the aforementioned oral lesions should lead to testing for HIV infection. PMID- 2185451 TI - Oral pemphigus vulgaris in a 6-year-old girl. AB - An extremely rare case of pemphigus vulgaris in a 6-year-old girl with prominent oral manifestations is presented. The disease was first noted at the age of 2 years, yet no diagnosis was made. Clinical, histopathologic, and immunologic criteria served to confirm the diagnosis. A review of the literature has revealed 22 well-documented cases of pemphigus vulgaris in children under the age of 17 years. It is concluded that although oral pemphigus vulgaris is rare in young persons, it must be included in the differential diagnosis in those cases that have a prolonged history of erosive or bullous lesions. PMID- 2185452 TI - A comparison of erythromycin and cefadroxil in the prevention of flare-ups from asymptomatic teeth with pulpal necrosis and associated periapical pathosis. AB - In a previous study by our group with patients having asymptomatic teeth with pulpal necrosis and an associated periapical radiolucent lesion (PN/PL), it was shown that prophylactic administration of penicillin V or erythromycin (high dose, 1-day regimen) resulted in a low incidence of flare-up (mean = 2.2%) and a low incidence of swelling and pain not associated with flare-up. No hypersensitivity responses occurred, and gastrointestinal side effects were found primarily with the erythromycins. To ascertain whether a single-dose administration of a long-acting 1-gm tablet of the cephalosporin antibiotic cefadroxil would result in a similar outcome, the present study was undertaken with 200 patients having quiescent PN/PL. The patients were randomly given either cefadroxil or erythromycin (base or stearate). Evaluations of flare-up were done 1 day, 1 week, and 2 months after endodontic treatment. A 2.0% flare-up incidence was found, with no statistically significant differences for cefadroxil (1.0%), stearate (2.0%), or base (4.0%). No hypersensitivity responses occurred. Gastrointestinal side effects were found primarily with the erythromycins (19.0%). The results showed that a 1-gm, single-dose regimen of cefadroxil was as effective as erythromycin and penicillin in preventing flare-ups and serious sequelae. A comparative analysis of the data from our first study (no peritreatment antibiotics) and the pooled data from our last three investigations (including the current trial) showed that peritreatment antibiotic coverage significantly reduced flare-ups and serious sequelae after endodontic treatment of asymptomatic PN/PL (p less than 0.001). PMID- 2185453 TI - Vertical root fractures. AB - In this study, I review, clinically and radiographically, 303 patients with 460 single or multirooted endodontically treated teeth. In all teeth, the therapy was performed by me with the use of final restoration of the crown with or without post and full cast crown coverage after treatment. The teeth were functioning for at least 3 years, without having received any other type of dental work since then. I evaluated the existence of vertical root fracture, the function of the teeth, the type of root canal therapy, the type and length of the post, and the type of retention of the post used in all 460 teeth. After statistical evaluation of the results, I found that 3.69% of the teeth had had vertical root fracture. Computer analysis, simple correlation hypothesis, and distribution method with 1 degree of freedom revealed significant correlation between vertical root fracture and the technique of instrumentation and obturation of the canal (p = 0.025), the length of the post (p = 0.05), and the existence of the post (p = 0.05). On the contrary, I found no correlation between root fracture and type of retention of the prefabricated post used with respect to the method of obturation. PMID- 2185454 TI - Gas gangrene. A review. AB - Gas gangrene continues to cause significant morbidity and mortality. This monograph reviews the entire spectrum of clostridial infection, including its etiology, pathophysiology, diagnosis, current recommended treatment, and prophylaxis. The early diagnosis of gas gangrene is paramount, as delay in aggressive combined treatment may result in death. PMID- 2185455 TI - Pediatric update #12. A simplified method for percutaneous epiphysiodesis. AB - Nine patients have undergone percutaneous epiphysiodesis using a 4.5-mm drill and image intensification fluoroscopy. The minimal surgical exposure resulted in minimal postoperative discomfort, excellent cosmesis, and complete closure of the physis in all patients in three to five months. No complications were encountered. The procedure is easy to perform and reliable. PMID- 2185456 TI - Arthroscopy update #6. Arthroscopy in the osteoarthritic knee. Long-term follow up. AB - A retrospective review was performed of 109 patients who underwent arthroscopic debridement of the knee for degenerative osteoarthritis. The results were evaluated using a modification of the Hospital for Special Surgery (HSS) scoring system as well as a subjective scale that measured the patients' degree of satisfaction with the procedure. Follow-up was obtained in 111 knees for an overall follow-up of 92% of knees. The mean age of the patients was 58.1 years, and the mean follow-up was 50.6 months. The overall results were 50 good, 20 fair, and 41 poor. Arthroscopic debridement offered measurable relief for 63% of the patients for a significant period of time. Although the results are equivocal by orthopaedic standards, 74% of the patients felt the procedure had been beneficial. PMID- 2185457 TI - Compilation of DNA sequences of Escherichia coli (update 1990). AB - We have compiled the DNA sequence data for E.coli available from the GENBANK and EMBL data libraries and over a period of several years independently from the literature. This is the second listing replacing and increasing the former listing roughly by one third. After deletion of all detected overlaps a total of 1 248 696 individual bp is found to be determined till the beginning of 1990. This corresponds to a total of 26.46% of the entire E. coli chromosome consisting of about 4,720 kbp. This number may actually be higher by some extra 2% derived from the sequence of lysogenic bacteriophage lambda and various insertion sequences. This compilation is now available in machine readable form from the EMBL data library. PMID- 2185458 TI - The placebo effect. Drug trial considerations. PMID- 2185459 TI - Mechanisms of bone degradation in infection: a review of current hypotheses. AB - Bone infection in clinical practice results in loss of structural integrity, leading to complications such as fracture and implant loosening. The biology of this process has received relatively little attention. In experimental models it seems clear that both polymorphonuclear leukocytes, whose effect predominates in the early stages, and mononuclear phagocytes are capable of bone degradation. An indirect effect by stimulation of physiologic mechanisms of resorption has not been ruled out, but the evidence points to direct degradation by inflammatory cell enzymes. PMID- 2185460 TI - Pulsed high frequency (27MHz) electromagnetic therapy for persistent neck pain. A double blind, placebo-controlled study of 20 patients. AB - In the majority of patients with neck pain, symptoms will resolve spontaneously or quite quickly in response to therapy. However, some patients' symptoms persist for a long period, irrespective of therapy. In this study, 20 patients with persistent (greater than 8 weeks) neck pain were enrolled in a double blind, placebo-controlled trial of low energy, pulsed electromagnetic therapy (PEMT)--a treatment previously shown to be effective in soft tissue injuries. For the first 3-week period, group A (10 patients) received active PEMT units while group B (10 patients) received facsimile placebo units. After 3 weeks, both pain (visual analogue scale (P less than .023) and range of movement (P less than .002) had improved in the group on active treatment compared to the controls. After the second 3 weeks, during which both groups used active units, there were significant improvements in observed scores for pain and range of movement in both groups. PEMT, in the form described, can be used at home easily in the treatment of patients with neck pain. It is frequently successful and without side effects. PMID- 2185461 TI - Clinical evaluation of the rocker bottom crutch. AB - One hundred fifty hospitalized patients referred to a physical therapy department for crutch walking instruction were evaluated in a randomized, controlled crossover study with "rocker bottom" and conventional axillary crutches. A large training effect was observed with each crutch, but no significant differences (all P greater than .05) of gait speed, stride length, heart rate, stability, or feeling of security were noted between the groups. Thus, rocker bottom crutches, despite potential stability and energy conservation benefits, were found to be no more effective than conventional axillary crutches in this hospital setting. PMID- 2185462 TI - Rheumatic fever revisited. PMID- 2185463 TI - Alloxan and ninhydrin inhibition of hexokinase from pancreatic islets and tumoural insulin-secreting cells. AB - Alloxan inhibited hexokinase activity in cytoplasmic fractions of transplantable radiation-induced rat islet cell tumours, ob/ob mouse pancreatic islets, rat liver and rat kidney. Half maximal inhibitory concentrations of alloxan were greater than those previously found for half maximal inhibition of pancreatic islet or liver glucokinase. D-glucose, preferentially the alpha-anomer, and D mannose protected hexokinase activity against alloxan inhibition. 1,4 Dithiothreitol completely protected against and partially reversed the alloxan inhibition of hexokinase. The ability of various dithiols to reverse the inhibition of hexokinase by alloxan was dependent on the spacing between the SH (thiol) groups. Only dithiols with intermediate spacing between the SH groups were effective. Dithiols with two vicinal SH groups such as 1,2-dimercaptoethane and 2,3-dimercaptopropanol (BAL) and dithiols with more widely spaced SH groups such as 1,5-dimercaptopentane were ineffective. Thus a reaction of alloxan with two SH groups in the sugar binding site of the hexokinase with the formation of a disulfide bond may be involved in the reversible inhibition of the enzyme. Ninhydrin also inhibited hexokinase from all four tissues studied. The half maximal inhibitory concentrations of ninhydrin were lower than those of alloxan. Inhibition of hexokinase may be an important factor in the general cytotoxic action of ninhydrin. However, inhibition of pancreatic islet hexokinase is unlikely to be the initial event in the pancreatic B-cell toxic action of alloxan, even if inhibition of hexokinase by high concentrations of alloxan may contribute to the B-cell toxic action.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185465 TI - The anaerobic ribonucleoside triphosphate reductase from Escherichia coli requires S-adenosylmethionine as a cofactor. AB - Extracts from anaerobically grown Escherichia coli contain an oxygen-sensitive activity that reduces CTP to dCTP in the presence of NADPH, dithiothreitol, Mg2+ ions, and ATP, different from the aerobic ribonucleoside diphosphate reductase (2'-deoxyribonucleoside-diphosphate: oxidized-thioredoxin 2'-oxidoreductase, EC 1.17.4.1) present in aerobically grown E. coli. After fractionation, the activity required at least five components, two heat-labile protein fractions and several low molecular weight fractions. One protein fraction, suggested to represent the actual ribonucleoside triphosphate reductase was purified extensively and on denaturing gel electrophoresis gave rise to several defined protein bands, all of which were stained by a polyclonal antibody against one of the two subunits (protein B1) of the aerobic reductase but not by monoclonal anti-B1 antibodies. Peptide mapping and sequence analyses revealed partly common structures between two types of protein bands but also suggested the presence of an additional component. Obviously, the preparations are heterogeneous and the structure of the reductase is not yet established. The second, crude protein fraction is believed to contain several ancillary enzymes required for the reaction. One of the low molecular weight components is S-adenosylmethionine; a second component is a loosely bound metal. We propose that S-adenosylmethionine together with a metal participates in the generation of the radical required for the reduction of carbon 2' of the ribosyl moiety of CTP. PMID- 2185464 TI - Merosin, a tissue-specific basement membrane protein, is a laminin-like protein. AB - Merosin is a basement membrane-associated protein found in placenta, striated muscle, and peripheral nerve. A 3.6-kilobase merosin cDNA clone was isolated from a placental cDNA expression library. The clone contained a 3.4-kilobase open reading frame, the 3' portion of which includes protein sequences of proteolytic fragments of merosin. The deduced amino acid sequence of the merosin polypeptide was similar to that of the COOH-terminal region of the 400-kDa A chain of laminin. This part of laminin forms the large globule at the end of the long arm of the laminin cross and is thought to contain the neurite-promoting site and the major cell binding site(s) in laminin. The sequence identity between merosin and the laminin A chain in this region is nearly 40%. An antiserum against a synthetic peptide from the middle of the merosin cDNA sequence identified a 300 kDa polypeptide in placental extracts, indicating that the merosin polypeptide is similar in size to the laminin A chain. Intact merosin was isolated from placental extracts and shown to be covalently associated with the laminin B chains and to have a cross-like structure similar to that of laminin. The similarities between merosin and laminin show that both proteins are members of the same family of basement membrane proteins. PMID- 2185467 TI - Inhibition of IgE synthesis by anti-IgE: role in long-term inhibition of IgE synthesis by neonatally administered soluble IgE. AB - Inoculation of syngeneic IgE into 2- to 12-day-old mice results in prolonged synthesis of anti-IgE antibodies without further challenge. These anti-IgE antibodies may be largely responsible for the long-term inhibition of synthesis of IgE that is known to result from a perinatal challenge with IgE. This conclusion is supported by the effect of passive inoculation of syngeneic polyclonal anti-IgE antibodies into young mice, which similarly results in selective inhibition of IgE synthesis. Further evidence is the close relationship between the age dependency of IgE-induced inhibition of subsequent IgE synthesis and the ability of IgE to induce anti-IgE antibodies. IgE synthesis was monitored at the level of secretion by B cells as well as serum IgE levels and IgE antibody responses. PMID- 2185466 TI - Transcriptional stimulation of the delta 1-crystallin gene by insulin-like growth factor I and insulin requires DNA cis elements in chicken. AB - Insulin-like growth factor I (IGF-I) and insulin regulate expression of the endogenous delta 1-crystallin gene in embryonic lens cells that express receptors for both peptides. To further analyze the transcriptional component of this hormonal effect, transient transfections of lens cells were prepared with DNA constructs containing deletions of the delta 1-crystallin promoter and the chloramphenicol acetyltransferase reporter gene. A 77-nucleotide DNA segment of the delta 1-crystallin promoter from nucleotide positions-120 to -43 confers sensitivity to insulin and IGF-I. The hormonal effect is dose-dependent, and maximal stimulation of promoter activity (2- to 2.5-fold induction) is obtained with 10(-8) M IGF-I and 10(-7) M insulin. Mobility-shift DNA-binding analysis shows specific binding of nuclear protein(s) to the delta 1-crystallin promoter DNA between positions -120 and +23, which appears to be regulated by IGF-I. An SP1-binding motif is involved in this DNA-protein interaction. The bivalent IgG fraction of an anti-insulin receptor antiserum (B-10), known to mimic insulin action in other systems, stimulates promoter activity to the same extent as insulin. PMID- 2185468 TI - Revision of the oligosaccharide structures of yeast carboxypeptidase Y. AB - The N-linked oligosaccharides from baker's yeast carboxypeptidase Y were analyzed by 1H NMR and specific mannosidase digestion and found to be identical to those from the Saccharomyces cerevisiae mnn9 mutant bulk mannoprotein. The results support the view that the mnn mutants make oligosaccharides that are a true reflection of the normal biosynthetic pathway and confirm that a recently revised yeast oligosaccharide structure is applicable to wild-type mannoproteins. PMID- 2185469 TI - Identification of a mammalian nuclear factor and human cDNA-encoded proteins that recognize DNA containing apurinic sites. AB - Damage to DNA can have lethal or mutagenic consequences for cells unless it is detected and repaired by cellular proteins. Repair depends on the ability of cellular factors to distinguish the damaged sites. Electrophoretic binding assays were used to identify a factor from the nuclei of mammalian cells that bound to DNA containing apurinic sites. A binding assay based on the use of beta galactosidase fusion proteins was subsequently used to isolate recombinant clones of human cDNAs that encoded apurinic DNA-binding proteins. Two distinct human cDNAs were identified that encoded proteins that bound apurinic DNA preferentially over undamaged, methylated, or UV-irradiated DNA. These approaches may offer a general method for the detection of proteins that recognize various types of DNA damage and for the cloning of genes encoding such proteins. PMID- 2185470 TI - Transcriptional effects of polyamines on ribosomal proteins and on polyamine synthesizing enzymes in Escherichia coli. AB - We find that the transcription of various ribosomal proteins can be differentially affected by polyamines and by changes in growth rates. Using strain MG1655 of Escherichia coli K-12 (F-, lambda-), we have determined the effects of polyamines and changes in growth rate on the transcription of several ribosomal genes and the polyamine-synthesizing enzymes ornithine decarboxylase (L ornithine carboxy-lyase; EC 4.1.1.17) and arginine decarboxylase (L-arginine carboxylyase; EC 4.1.1.19). Ribosomal proteins S20 and L34 can be differentiated from the other ribosomal proteins studied; the transcription of S20 and L34 is especially sensitive to polyamines and less sensitive to changes in growth rates. In contrast, the transcription of S10, S15, S19, L2, L4, L20, L22, and L23 is insensitive to polyamines although it is particularly sensitive to changes in growth rates. Like S20 and L34, the transcription of ornithine decarboxylase and arginine decarboxylase is especially sensitive to polyamines. Polyamines specifically enhance the transcription of ribosomal proteins S20 and L34, and decrease that of ornithine decarboxylase and arginine decarboxylase. It is evident that polyamines can exert both positive and negative regulation of gene expression in E. coli that can be differentiated from the effects caused by changes in growth rates. PMID- 2185471 TI - Plasma membrane fatty acid-binding protein and mitochondrial glutamic-oxaloacetic transaminase of rat liver are related. AB - The hepatic plasma membrane fatty acid-binding protein (h-FABPPM) and the mitochondrial isoenzyme of glutamic-oxaloacetic transaminase (mGOT) of rat liver have similar amino acid compositions and identical amino acid sequences for residues 3-24. Both proteins migrate with an apparent molecular mass of 43 kDa on SDS/polyacrylamide gel electrophoresis, have a similar pattern of basic charge isomers on isoelectric focusing, are eluted similarly from four different high performance liquid chromatographic columns, have absorption maxima at 435 nm under acid conditions and 354 nm at pH 8.3, and bind oleate with a Ka approximately 1.2-1.4 x 10(7) M-1. Sinusoidally enriched liver plasma membranes and purified h-FABPPM have GOT enzymatic activity; the relative specific activities (units/mg) of the membranes and purified protein suggest that h-FABPPM constitutes 1-2% of plasma membrane protein in the rat hepatocyte. Monospecific rabbit antiserum against h-FABPPM reacts on Western blotting with mGOT, and vice versa. Antisera against both proteins produce plasma membrane immunofluorescence in rat hepatocytes and selectively inhibit the hepatocellular uptake of [3H]oleate but not that of [35S]sulfobromophthalein or [14C]taurocholate. The inhibition of oleate uptake produced by anti-h-FABPPM can be eliminated by preincubation of the antiserum with mGOT; similarly, the plasma membrane immunofluorescence produced by either antiserum can be eliminated by preincubation with the other antigen. These data suggest that h-FABPPM and mGOT are closely related. PMID- 2185473 TI - Conservation of the regulatory subunit for the Clp ATP-dependent protease in prokaryotes and eukaryotes. AB - Bacteria, tomatoes, and trypanosomes all contain genes for a large protein with extensive homology to the regulatory subunit, ClpA, of the ATP-dependent protease of Escherichia coli, Clp. All members of the family have between 756 and 926 amino acids and contain two large regions, of 233 and 192 amino acids, each containing consensus sequences for nucleotide binding. Within these regions there is at least 85% similarity between the most distant members of the family. The high degree of similarity among the ClpA-like proteins suggests that Clp-like proteases are likely to be important participants in energy-dependent proteolysis in prokaryotic and eukaryotic cells. PMID- 2185472 TI - Cloning and expression of a mammalian peptide chain release factor with sequence similarity to tryptophanyl-tRNA synthetases. AB - The termination of protein synthesis is encoded by in-frame nonsense (stop) codons. Most organisms use three nonsense codons: UGA, UAG, and UAA. In contrast to sense codons, which are decoded by specific tRNAs, nonsense codons are decoded by proteins called release factors (RFs). Here we report the cloning of a mammalian RF cDNA by the use of monoclonal antibodies specific for rabbit RF. Functional studies showed that, when expressed in Escherichia coli, the protein encoded by this cDNA has in vitro biochemical characteristics similar to those of previously characterized mammalian RFs. DNA sequencing of this eukaryotic RF cDNA revealed a remarkable sequence similarity to bacterial and mitochondrial tryptophanyl-tRNA synthetases, with the greatest similarity confined to the synthetase active site, and no obvious similarity to bacterial RFs. PMID- 2185474 TI - Molecular mechanisms of DNA repair inhibition by caffeine. AB - Caffeine potentiates the mutagenic and lethal effects of genotoxic agents. It is thought that this is due, at least in some organisms, to inhibition of DNA repair. However, direct evidence for inhibition of repair enzymes has been lacking. Using purified Escherichia coli DNA photolyase and (A)BC excinuclease, we show that the drug inhibits photoreactivation and nucleotide excision repair by two different mechanisms. Caffeine inhibits photoreactivation by interfering with the specific binding of photolyase to damaged DNA, and it inhibits nucleotide excision repair by promoting nonspecific binding of the damage recognition subunit, UvrA, of (A)BC excinuclease. A number of other intercalators, including acriflavin and ethidium bromide, appear to inhibit the excinuclease by a similar mechanism--that is, by trapping the UvrA subunit in nonproductive complexes on undamaged DNA. PMID- 2185475 TI - Hydrolysis of GTP by p21NRAS, the NRAS protooncogene product, is accompanied by a conformational change in the wild-type protein: use of a single fluorescent probe at the catalytic site. AB - 2'(3')-O-(N-Methyl)anthraniloylguanosine 5'-triphosphate (mantGTP) is a fluorescent analogue of GTP that has similar properties to the physiological substrate in terms of its binding constant and the kinetics of its interactions with p21NRAS, the NRAS protooncogene product. There is a 3-fold increase in fluorescence intensity when mantGTP binds to p21NRAS. The rate constant for the cleavage of mantGTP complexed with the protein is similar to that of GTP, and cleavage is accompanied by a fluorescence intensity change in the wild-type protein complex. A two-phase fluorescence change also occurs when the nonhydrolyzable analogue 2'(3')-O-(N-methyl)anthraniloylguanosine 5'-[beta, gamma imido]triphosphate (mantp[NH]ppG) binds to wild-type p21NRAS. The second phase occurs at the same rate as the second phase observed after mantGTP binding. Thus this second phase is probably a conformation change of the p21NRAS nucleotiside triphosphate complex and that the change controls the rate of GTP hydrolysis on the protein. With a transforming mutant, [Asp12]-p21NRAS, there is no second phase of the fluorescence change after mantGTP or mantp[NH]ppG binding, even though mantGTP is hydrolyzed. This shows that an equivalent conformational change does not occur and thus the mutant may stay in a "GTP-like" conformation throughout the GTPase cycle. These results are discussed in terms of the proposed role of p21NRAS in signal transduction and the transforming properties of the mutant. PMID- 2185476 TI - Sexual reproduction as an adaptation to resist parasites (a review). AB - Darwinian theory has yet to explain adequately the fact of sex. If males provide little or no aid to offspring, a high (up to 2-fold) extra average fitness has to emerge as a property of a sexual parentage if sex is to be stable. The advantage must presumably come from recombination but has been hard to identify. It may well lie in the necessity to recombine defenses to defeat numerous parasites. A model demonstrating this works best for contesting hosts whose defense polymorphisms are constrained to low mutation rates. A review of the literature shows that the predictions of parasite coevolution fit well with the known ecology of sex. Moreover, parasite coevolution is superior to previous models of the evolution of sex by supporting the stability of sex under the following challenging conditions: very low fecundity, realistic patterns of genotype fitness and changing environment, and frequent mutation to parthenogenesis, even while sex pays the full 2-fold cost. PMID- 2185479 TI - [Hemoglobin niosomes. II. In vitro interactions of plasma proteins and phagocytes]. AB - We have studied the in vitro interactions versus some blood components of the hemoglobin niosomes whose preparation and physicochemical and oxyphoric properties have been published in a precedent paper (this journal, 1989, No. 7, p. 192). This work was devoted to the research of 1) Agglutination phenomena with ABO blood group substances, plasma, some of its components and three plasma expanders, finally main erythrocytic phenotypes. 2) Adsorption of plasma proteins by immunoelectrophoresis. 3) Effects of niosomes on blood coagulation by thromboelastography. 4) Interactions between niosomes and phagocytes by electron microscopy, chemotactic migration, oxygen consumption, superoxide generation and oxydases function. These assays allow to observe and conclude that: 1) The agglutination phenomena are almost constant except with red blood cells. The agglutinates are dissociable by shaking. The agglutination appears to be nonspecific of a niosome component but is not observed with "classical" DPPC-chol DCP liposomes. 2) Albumin and eventually transferrin are adsorbed at the surface of niosomes but without destabilizing them. 3) The vesicules show no important effects on coagulation factors, the enhancement of clotting time appearing essentially the consequence of blood dilution. 4) Niosomes phagocytosis is important but all the measurements fail to show any cellular metabolism activation: cell oxygen consumption, oxygenated metabolites generation and oxydases activity are not enhanced whatever the "electric" charge or the niosomes/phagocytes ratio used. PMID- 2185477 TI - Differential effects of the cytoplasmic domains of cell adhesion molecules on cell aggregation and sorting-out. AB - Cell adhesion molecules (CAMs) are cell surface glycoproteins that play important roles in morphogenesis and histogenesis, particularly in defining discrete borders between cell populations. Previous studies have suggested that the cytoplasmic domains of CAMs play a significant role in their adhesion properties. These domains may also be involved in regulating other cellular interactions, such as those involved in the sorting-out of cells to form tissues. In the present studies, we have compared the effects of replacing the cytoplasmic domain of one CAM with that of another CAM of different homophilic binding specificity on cell adhesion and cell sorting-out. The molecules studied were liver CAM (L CAM) and the neural CAM (N-CAM) sd polypeptide. One cDNA was constructed that encodes a chimeric molecule composed of the extracellular domain of L-CAM and the cytoplasmic plus transmembrane domains of the sd polypeptide of chicken N-CAM (called L/N-CAM). Another was constructed encoding a truncated L-CAM missing the last 50 residues of the cytoplasmic domain. Permanently transfected lines of mouse L cells were obtained expressing the truncated L-CAM ("L-L-50 cells") or the chimeric L/N-CAM ("L-L/N cells") and were compared with cells expressing intact L-CAM ("L-L cells"). Immunoblotting and ELISA analyses demonstrated that these various cell lines expressed similar amounts of CAMs at the cell surface. Aggregation of L-L and L-L/N cells occurred at similar rates in short-term aggregation assays and was inhibited by antibodies to the extracellular L-CAM binding domain. In contrast, L-L-50 cells did not aggregate. Incubation of transfected cells with cytochalasin D, which disrupts microfilaments, markedly inhibited aggregation of L-L cells but had no effect on L-L/N cell aggregation. Mixed L-L and L-L/N cells co-aggregated in short-term assays; in the longer-term sorting-out assays, however, they behaved differently: L-L cells sorted out from both L-L/N and untransfected cells, whereas L-L/N cells did not sort out from untransfected cells. These studies not only suggest that interactions of cytoplasmic domains of different CAMs with the cytoskeleton can modulate cell adhesion but also suggest that specific interactions with certain cytoskeletal components are required for events such as cell sorting and cell patterning. PMID- 2185478 TI - Autoantibodies from a patient with scleroderma CREST recognized kinetochores of the higher plant Haemanthus. AB - Human autoantibodies from a patient with scleroderma CREST (calcinosis, Raynaud phenomenon, esophageal dismotility, sclerodactyly, telangiectasia) were used to immunostain kinetochores on chromosomes in endosperm of the seed of the monocot Haemanthus katherinae Bak. Kinetochores of mitotic chromosomes and prekinetochores of interphase cells were specifically stained using conventional indirect immunofluorescence procedures as well as a nonfading immunogold-silver enhanced technique and analyzed by fluorescence and video microscopy. In interphase, prekinetochores were either single or double structures depending on the stage of the cell cycle but became quadruple (two distinct stained dots on each chromatid) in mid-to-late prophase. In favorable preparations of prometaphase chromosomes, multiple subunits could be resolved within each sister kinetochore suggesting a compound organization. Western blot analysis demonstrated common epitopes in centromeric peptides of HeLa and Haemanthus cell extracts. Although the molecular mass of individual polypeptides differed in the two species, the presence of shared epitopes indicates striking conservation of centromere/kinetochore components throughout evolution. PMID- 2185480 TI - [Collection and verification--pharmacy history museums in East and West Germany]. PMID- 2185481 TI - [Narcolepsy--syndrome, therapy, risks and secondary effects]. PMID- 2185482 TI - [Cellulose, an interesting excipient for pharmaceutic use]. PMID- 2185483 TI - [Chemistry and pharmacology of hydrazinoacetic acid]. PMID- 2185484 TI - [The effect of cimetidine on pharmacokinetics of other drugs]. PMID- 2185485 TI - [The thiocyanate ion as a physiologically significant active substance in living nature]. PMID- 2185486 TI - Antimicrobial activity of essential oils from greek Sideritis species. PMID- 2185487 TI - Pharmacology of cyclosporine (sandimmune). I. Introduction. PMID- 2185488 TI - Pharmacology of cyclosporin (sandimmune). II. Chemistry. PMID- 2185489 TI - Pharmacology of cyclosporine (sandimmune). III. Immunochemistry and monitoring. PMID- 2185490 TI - Pharmacology of cyclosporine (sandimmune). IV. Pharmacological properties in vivo. PMID- 2185491 TI - Pharmacology of cyclosporine (sandimmune). V. Pharmacological effects on immune function: in vitro studies. PMID- 2185492 TI - Pharmacology of cyclosporine. VI. Cellular activation: regulation of intracellular events by cyclosporine. PMID- 2185493 TI - Pharmacology of cyclosporine (sandimmune). VII. Pathophysiology and toxicology of cyclosporine in humans and animals. PMID- 2185494 TI - Evaluation of the teratogenic potential of chemicals in the rat. AB - On the basis of the results of a variety of teratogenicity studies in Sprague Dawley-derived albino rats, carried out over several years in our laboratory, an appraisal of the principal experimental procedures is set forth. Various categories of chemicals were used for the evaluation of dosage-related teratogenic potency. Salicylate, prednisolone, cyclophosphamide, 5 hydroxytryptamine (serotonin), glycinonitrile, and dimethylformamide have proven to be teratogenic under certain of the experimental conditions used. Particular differences in the embryotropic effects of acetylsalicylic acid were caused by qualitative and quantitative changes of the vehicle. Fetal morphological abnormalities, classified either as 'malformations' or as 'anomalies', may occur independently of overt maternal toxicity and/or embryotoxicity. Further, they may be closely correlated with general inhibitory effects on growth. Drugs may affect developing tissues and organs selectively due to their pharmacological activity and/or specific organ toxicity. The limitation of maternal treatment to a very short period of gestation may disclose a specific susceptibility of developmental stages of the embryo or fetus. Finally, the importance of data collected from a historical control population to the interpretation of teratogenicity data is emphasised. PMID- 2185495 TI - Reduction of chronic posttraumatic hand edema: a comparison of high voltage pulsed current, intermittent pneumatic compression, and placebo treatments. AB - The purpose of this study was to compare the efficacy of intermittent pneumatic compression (IPC) and high voltage pulsed current (HVPC) in reducing chronic posttraumatic hand edema. Thirty patients with posttraumatic hand edema were randomly assigned to IPC, HVPC, or placebo-HVPC groups (10 patients in each group). Patients received a single application of the respective treatment for 30 minutes. Measurements were made before and after a 10-minute rest period and after the 30-minute treatment. A volumetric method was used to quantify edema reduction. Reduction in hand edema was significant between the IPC and placebo HVPC groups (p = .01). Differences in edema reduction between the HVPC and placebo-HVPC groups did not reach statistical significance (p = .04), but were considered clinically significant. There was no significant difference between the IPC and HVPC groups. A single 30-minute administration of IPC produced a significant reduction in hand edema. Additional clinical studies are needed to delineate maximally effective treatment protocols for reduction of chronic posttraumatic hand edema. [Griffin JW, Newsome LS, Stralka SW, et al: Reduction of chronic posttraumatic hand edema: A comparison of high voltage pulsed current, intermittent pneumatic compression, and placebo treatments. PMID- 2185496 TI - In situ hybridization histochemistry and the study of gene expression in the human brain. PMID- 2185497 TI - Neural basis of sound pattern recognition in anurans. PMID- 2185498 TI - Drug-induced neurological disorders. PMID- 2185499 TI - [Oncogenes and neuronal differentiation]. PMID- 2185500 TI - Differentiating anxiety and depression. PMID- 2185501 TI - Epidemiology of panic disorder and agoraphobia. PMID- 2185502 TI - The comorbidity and mortality of panic disorder. PMID- 2185503 TI - Panic disorder in cardiology patients. AB - This paper reviews current evidence from several cardiology populations that suggests panic disorder is prevalent and underdiagnosed. Cardiology patients with atypical angina and no heart disease have a high likelihood of having panic disorder as suggested by studies of two separate cardiology populations. That they resemble psychiatric populations with panic is suggested by their positive response to alprazolam. Although evidence is less clear concerning the relationship between MVP and panic, it appears that patients referred to ECHO and found to have MVP are also likely to have panic. Three other populations deserving further study are patients with 1) pacemaker syndrome, 2) coronary artery disease with atypical angina and 3) certain arrhythmias. PMID- 2185504 TI - Anxiety and bereavement. AB - The results reported here support the observations that anxiety symptoms are prevalent, often severe, and may last through at least the first seven months of bereavement. In addition, many widows and widowers are prescribed, or take on their own, medications geared to attenuate the discomfort of these symptoms. A preliminary profile of persons most likely to suffer substantial and relatively prolonged anxiety after the stress of widowhood includes: someone who is young, female and experiences a loss of income related to the death; someone who lacks social support; and someone who experiences acute grief, a depressive syndrome and anxiety symptoms at the end of two months. We hope to build on this profile over time, so that vulnerable individuals might be identified and offered early intervention. PMID- 2185505 TI - The measurement of inhibin. PMID- 2185506 TI - Water quality criteria for 2,4,6-trinitrotoluene. AB - The occurrence of the munitions compound 2,4,6-trinitrotoluene (TNT) in groundwater and surface water surrounding U.S. Army ammunition plants may result in contamination of local drinking water supplies. TNT exerts its primary toxic effect in humans on the hematologic system and liver, but it is also known to cause gastrointestinal effects and cataracts. Health effects data were analyzed for TNT and although no controlled human studies exist concerning the acute or chronic toxic effects of exposure to TNT, sufficient animal toxicity data are available to derive an ambient water quality criterion for the protection of human health. This paper summarizes the available literature on metabolism and toxicity of TNT in humans and animals. Based on noncarcinogenic mammalian toxicity data, and following the methodologies of the U.S. Environmental Protection Agency, an ambient water quality criterion for the protection of human health of 135 micrograms/liter is proposed when consumption of both contaminated water and fish is anticipated. For drinking water alone, the proposed criterion is 140 micrograms/liter. PMID- 2185507 TI - Comparison of water quality criterion and lifetime health advisory for hexahydro 1,3,5-trinitro-1,3,5-triazine (RDX). AB - The U.S. Environmental Protection Agency (USEPA) has recently recommended a lifetime health advisory (HA) for hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). The purpose of this brief article is to present the basis for the calculation of the HA so that the reader can compare it with a water quality criterion (WQC) that has been proposed (E. L. Etnier, 1989, Regul. Toxicol. Pharmacol. 9, 147 157). In the earlier article, a water quality criterion of 105 micrograms/liter for RDX in drinking water was proposed, and in the present article the methodology by which USEPA calculated a lifetime HA of 2 micrograms/liter is presented. The differences in the derivation of the WQC and the HA are discussed. PMID- 2185508 TI - The myth of the final hazard assessment. AB - Hazard assessment is a basic tool used in the evaluation and regulation of chemicals, but in spite of this there are many different interpretations of the scope and function of a hazard assessment. Starting from a discussion of the essential elements and conceptual frames involved, an attempt is made to identify the sources of uncertainty that are inherent in a hazard assessment. Problems identified include unambiguous identification of the chemical source, the routes of exposure, and the possible targets to be considered. Inadequacies in effects data are frequent, but unlike many of the other sources of uncertainty, these are often compensated for by the use of safety factors when setting quantitative limits for human or environmental exposure. The inherent uncertainties in the process make periodic revisions of any hazard assessment process inevitable, as new knowledge on routes of exposure and targets becomes available. PMID- 2185509 TI - Hazard evaluation for complex mixtures: relative comparisons to improve regulatory consistency. AB - The traditional "absolute decision-making" process used by federal regulatory agencies to derive permissible exposure concentrations for hazardous substances is initiated by an evaluation of the "weight-of-evidence" that a substance is a potential human carcinogen. Subsequent conservative procedures applied variably to noncarcinogens and carcinogens yield exposure limits for individual substances based on "data-sparse, model-intensive" techniques which may lack consistency and have difficulty directly addressing the hazards from complex mixtures. This paper describes how a "relative decision-making" technique applicable to complex mixtures can supplement the "absolute" approach currently used. Estimates obtained through this "data-intensive, model-sparse" technique may be evaluated by comparisons to estimates representing a range of hazards "generally regarded as safe" derived through analyses of chlorinated drinking water, cigarette smoke condensate, and other common human exposures. Comparisons are also used to evaluate the relative degree of consistency in risk estimates between 58 suspect human carcinogens analyzed by the U.S. Environmental Protection Agency Carcinogen Assessment Group and by the authors. PMID- 2185510 TI - Regulation of food-related carcinogens in Japan. AB - Use of hazardous environmental substances in Japan is regulated, based on their risk assessment, by laws of various ministries, depending upon the chemicals concerned. Food additives and food contaminants are controlled by the Food Sanitation Law of the Ministry of Health and Welfare. When manufacture or import of new food additives is intended, their physicochemical and biological data are evaluated by the Food Sanitation Investigation Council. When new data become available on the carcinogenicity of food additives that have been approved and are in use, these compounds are reevaluated. Between 1974 and 1986, twelve chemicals were proved to be carcinogenic in Japan by task groups for evaluation of the carcinogenicity of food additives, medical drugs and pesticides, which were organized by the Ministry of Health and Welfare. Of these compounds, 2-(2 furyl)-3-(5-nitro-2-furyl)acrylamide was banned from use, but use of hydrogen peroxide and potassium bromate was permitted, provided that these compounds were decomposed or removed from the final products. The use of butylated hydroxyanisole within fixed limits in some foodstuffs was also permitted. Decisions on the use of these compounds were based on the prevailing opinion on carcinogens at the time. This paper reports these facts with a consideration of future problems on the regulation of food carcinogens. PMID- 2185511 TI - Assessing the contribution from lead in mining wastes to blood lead. AB - Lead has been recognized for years as an environmental pollutant of concern for young children. Nonetheless, many children in the United States still experience high body burdens of lead. Reducing exposure to lead must include an assessment of all potential sources of lead and a definition of routes of exposure. In this paper, the relationships between soil lead and blood lead concentrations in residents in communities with high soil lead concentrations resulting from past mining and ore processing (milling) activities are compared to those derived from studies in urban communities or communities with operating smelters. The impact of mine waste-derived lead in soil (usually in the form of lead sulfide) on blood lead is less than that for lead in soil derived from smelter, vehicle, or paint sources. Possible reasons for a reduced impact of lead sulfide on blood lead in children in mining communities include the following: lead from mining sources contributes less to lead in the immediate environment of children than lead from other sources; mine wastes typically are of larger particle size, which decreases the bioavailability of lead in the gastrointestinal tract; and lead sulfide is absorbed less in the gastrointestinal tract compared to other lead species. A reduced impact of mine waste-derived lead on blood lead may be important from a regulatory point of view. Expensive cleanup actions for lead-contaminated soils in mining communities based on acceptable soil lead concentrations derived from smelter or urban communities may be questionable in terms of reducing blood lead in children. PMID- 2185512 TI - Uncertainty in health risk assessments. AB - Considerable scientific evidence has accumulated in the area of risk assessment. Using physiologically based pharmacokinetic models and biologically based dose response models, more precise estimates of risk are becoming available. Uncertainty analysis performed at three steps of the process will enhance a clearer understanding of the assumptions being made regarding a public health decision. Recommendations are made on how uncertainty in risk assessments can be addressed and the types of future research that are required to this end. PMID- 2185513 TI - Some regulatory definitions of risk: interaction of scientific and legal principles. AB - This paper discusses definitions of risk evolved to accommodate legal principles and scientific development in a time of rapid advances in science. The legal principles that underlie the interrelated definitions of "safe," "significant risk," and "acceptable risk" are examined in light of the major court decisions on benzene and vinyl chloride. The separate origins and development of concepts of de minimis risk and "negligible risk" are examined. The legal definitions are consistent with a judgmental weight-of-the-evidence evaluation of the statutory criteria, the available scientific information, and the risks acceptable in the world in which we live. The legal principles are dynamic, encourage scientific risk assessment based on case-by-case evaluation of the magnitude and character of human risks, and encourage incorporation of new scientific developments in the evaluation to improve the science base for regulatory decisions. PMID- 2185514 TI - A review of correlates of alcohol use and alcohol problems in adolescence. AB - The literature on correlates of adolescent alcohol use has generally identified similar correlates, despite differences in types of populations studied, definitions of both alcohol use and potential correlates, and time periods over which use is assessed. Still at issue, however, is the relative importance of each correlate. This chapter summarizes the principal findings from recent literature about demographic, social, and psychiatric correlates of adolescent alcohol use. Given that part of an effective national antidrug policy will be curbing society's appetite for drugs, which begins in adolescence and in which alcohol plays a large role, it is a propitious time to call for more intensive inquiry into the mechanisms underlying the above-identified correlates of adolescent alcohol use. PMID- 2185515 TI - Drug use and its social covariates from the period of adolescence to young adulthood. Some implications from longitudinal studies. AB - This chapter presents a review and discussion of the dynamic relationship between drug use, especially the use of illicit drugs, and its social covariates from the period of adolescence to young adulthood. The discussion is based primarily on longitudinal studies. In particular, I include a review and discussion of my collaborative studies with Kandel, in which we employ life-course perspectives for the analysis of natural drug and life histories of individuals based on event history models. Specifically, I discuss five covariates: (1) age, (2) onset age of drug use, (3) historical period, (4) family and work roles, and (5) influence of significant others, with the dynamic interdependence between drug use and family and work roles as the major topic of discussion. The discussion also includes some insights into the issue of causation vs. selection effects regarding the influence of drug use on life-course pattern, and presents a novel aspect of indirect effects in the analysis of the determinants of drug use progression. PMID- 2185516 TI - Longitudinal patterns of alcohol use by narcotics addicts. AB - Longitudinal patterns of alcohol use by narcotics addicts sampled from a drug free treatment program and from several methadone maintenance treatment programs were examined. Overall, a high prevalence of alcohol use was found in both samples across several stages of the addicts' careers. Many addicts were also using nonnarcotic drugs and marijuana concurrently. Generally, levels of alcohol, as well as of other substances use, decreased as the narcotics addiction career began. Unlike other drug use, however, only alcohol consumption increased whenever a decrease occurred in narcotics use. Effects of ethnicity, gender, parental alcohol problems, and opiate and alcohol use onset sequence on the alcohol- and narcotics-related behavior are examined in detail. A pattern of early onset of heavy alcohol consumption before initial narcotics addiction was more common among Chicanos and was associated with a positive parental alcohol history. Women addicts typically had a much lower alcohol consumption level than their male counterparts. Among the 160 deaths of the original 581 addicts followed during the 20 years of the study, alcohol-related deaths accounted for 17.5% of the total. Treatment implications for addicts with an alcohol problem are discussed. PMID- 2185517 TI - Problem drinking and alcohol problems. Widening the circle of covariation. AB - This chapter reviews research pertaining to two basic premises regarding problem drinking: that a conceptual clarification is necessary, one which makes an explicit distinction between drinking behavior and alcohol-related problems or adverse consequences, and that an adequate theory of problem drinking must extend beyond the alcohol-specific theories to a broad matrix of biological, behavioral, psychological, and social variables. Both cross-sectional and longitudinal studies of drinking in nonclinical populations show that levels of alcohol consumption are only moderately related to alcohol-related adverse consequences, and that a broad array of variables mediate the extent to which normal-population drinkers will be vulnerable to alcohol problems. Factors contributing to differential vulnerability to alcohol problems include the concurrent use of other drugs, engaging in other problem behaviors, personality characteristics such as impulsivity, prior depression, and a lack of social conformity or conventionality, the lack of a protective family environment, stress, and being female. A model of problem drinking consisting of overlapping, but distinct sets of predictors for drinking behavior and alcohol-related adverse consequences is proposed. PMID- 2185518 TI - Behavioral aspects of alcohol-tobacco interactions. AB - Alcohol and tobacco consumption are correlated-smokers consume more alcohol than do nonsmokers and alcohol consumers smoke more than do teetotalers. In addition, heavy drinking tends to be associated with heavy smoking. A large majority of alcoholics, who by definition are heavy drinkers, smoke. A number of studies examining the effects of ethanol pretreatment or availability on tobacco consumption have demonstrated that ethanol potentiates tobacco consumption. Whether smoking potentiates alcohol consumption is not known. Possible mechanisms underlying the alcohol/tobacco association, including cross-tolerance between the two drugs, are discussed. Tobacco appears to counteract the deleterious effects of alcohol on some measures of performance. The association between alcohol and tobacco consumption may have some relevance regarding the issue of relapse to either one of the drugs. Finally, combined use of alcohol and tobacco presents greater risk of certain diseases than the sum of the excess risks of alcohol and tobacco considered individually. PMID- 2185519 TI - Interactions of ethanol and nicotine at the receptor level. AB - Several studies have demonstrated that alcohol use is generally accompanied by an increase in smoking in humans. In rats, nicotine administration increases alcohol consumption. Genetic evidence from animal studies also suggests ethanol-nicotine interactions in that mouse lines that were selectively bred for differential sensitivity to ethanol also differ in sensitivity to nicotine. In addition, animals that have been chronically treated with alcohol are cross-tolerant to some of the actions of nicotine and chronic nicotine-treated animals are cross tolerant to alcohol. This review summarizes the data which indicate that lipids and lipid membranes modify the binding of nicotinic agonists and antagonists to non-neuronal nicotinic receptors as well as modifying the function of these well characterized receptors. These results suggest that studies of ethanol disruption of membrane lipid regulation of brain nicotinic receptor binding, structure, and function may provide insights into why humans frequently use and abuse alcohol and tobacco together. PMID- 2185520 TI - Cultural factors in the choice of drugs. AB - The human animal has discovered a wide range of drugs, some of which are readily available products of nature, and has invented others by means of manufacture or processing. The meanings, uses, and associations that are attached to such drugs vary from one population to another and are often different for subgroups within a given population. Even the effects of drugs vary, demonstrating that they are not inherent in the substances or in the biochemical impact they have on the human organism. Meanings, uses, and associations often change over time as well. These facts, briefly illustrated with selected examples, demonstrate that culture is an important aspect of the environment--interacting with biological and psychological factors--in relation to choices individuals make about drugs, their uses, and the outcomes of use. The concept of culture has heuristic value in describing and analyzing beliefs and behavior, but it should not be construed as an etiologically powerful entity. Culture can be viewed as a metaphor, reflecting and incorporating social consensus and controls. Any serious attempt to change patterns of drug use must involve changes in the culture, and education promises to be the most likely way of altering both individual choices and cultural patterns. Whereas "the control model" of prevention unrealistically relies on formal legislative and regulatory controls, "the sociocultural model" emphasizes more powerful informal social controls. PMID- 2185521 TI - Self-regulation and self-medication factors in alcoholism and the addictions. Similarities and differences. AB - Addicts and alcoholics suffer vulnerabilities and deficits in self-regulation. A principal manifestation of their self-regulation disturbances is evident in the way they attempt to self-medicate painful affect states and related psychiatric problems. Individuals select a particular drug based on its ability to relieve or augment emotions unique to an individual which they cannot achieve or maintain on their own. Addicts and alcoholics usually experiment with all classes of drugs, but discover that a particular drug suits them best. Usually, painful affect states interact with other problems in self-regulation involving self-esteem, relationships, self-care, and related characterological defenses, making it more likely that addicts will experiment with and find the action of a particular drug appealing or compelling. Stimulants have their appeal because their energizing properties relieve distress associated with depression, hypomania, and hyperactivity; opiates are compelling because they mute and contain disorganizing affects of rage and aggression; and sedative hypnotics, including alcohol, permit the experience of affection, aggression, and closeness in individuals who are otherwise cut off from their feelings and relationships. PMID- 2185522 TI - Treating combined alcohol and drug abuse in community-based programs. AB - The key issues in effective treatment of combined alcohol and drug abuse are identified as comprehensive diagnosis, effective services, and long-term recovery. Empirical data from community-based alcohol and drug treatment studies are presented, illustrating the extent of combined abuse, the lack of treatment for combined abuse, and the negative effects of combined abuse on treatment outcomes. Reconsideration is given to issues such as the concentration of diagnosis on a primary pattern of abuse, the orientation toward concurrent treatment of combined abuse, the requirement of immediate abstinence vs. gradual reduction of combined abuse patterns, and the role of relapse in recovery from combined abuse. PMID- 2185523 TI - Behavioral treatment of alcohol and drug abuse. What do we know and where shall we go? AB - Over the last 20 years there has been a substantial increase in the use of alcohol and drugs in industrialized nations and a concomitant shift in the emphasis of treatment for alcohol and drugs. Rather than seeking treatment for alcohol alone or a single class of drug, many individuals are seeking treatment for alcohol and/or a number of drugs. While theoreticians have been exploring the similarities in the addictive behaviors, clinical researchers are only just beginning to do so. Unfortunately, most treatment research has focused almost exclusively on alcohol abusers or drug abusers, with little research conducted to date with alcohol and drug abusers. Behavioral interventions developed for alcohol abuse are now being tested with drug abusers, and vice versa. The purpose of this chapter is fourfold: (1) to briefly discuss the similarities in the assessment of alcohol and drug abuse; (2) to describe behavioral interventions that have been supported by research and briefly review this treatment outcome research; (3) to discuss the theoretical similarities in behavioral interventions for alcohol and drug abuse; and (4) to make recommendations for future advancements in treatment and research. PMID- 2185524 TI - The dependence syndrome concept as applied to alcohol and other substances of abuse. AB - The dependence syndrome concept has been defined by both behavioral and biological changes that occur with excessive substance use. Originally developed for alcohol, this concept was adopted for diagnosing dependence on other substances of abuse, although little research had been done to test its validity for other drugs. This chapter addresses the validity of the dependence concept across drug classes in the following ways. First, we compare the dependence items for three different drugs, alcohol, opiates, and cocaine, in measures of internal consistency. Second, biological items are correlated with behavioral items to assess the usefulness of defining dependence by both biological and behavioral criteria. Finally, we draw upon ideas developed in motivational theory and apply these to the dependence syndrome concept. These analyses, while supporting the validity of the concept, lead to suggestions for refining the concept of dependence. PMID- 2185525 TI - The behavioral pharmacology of alcohol and other drugs. Emerging issues. AB - Alcohol and other drugs are compared with respect to their abuse liability and dependence potential. Drug-reinforced behavior is defined, and factors related to the establishment of this behavior that have received increasing experimental attention in recent years are reviewed. Acquisition techniques, schedule of access, route of self-administration, and organism factors, such as species, gender, and genetic background, are discussed. Other areas of emerging interest are the effect of feeding regimens, alternative reinforcers, and social conditions on drug-reinforced behavior. Also, biochemical factors such as neurochemical alterations, hormonal changes, and alcohol and other drug combinations, are considered. Finally, dependence potential is considered in terms of observational changes and performance alterations that seem to be sensitive indicators of the protracted aspects of drug withdrawal. The relationship between drug-seeking behavior and withdrawal is examined. PMID- 2185526 TI - [Right ventricular function and effort tolerance in patients with chronic congestive heart insufficiency. A cross-over double-blind study]. AB - We tried to assess the value of both ventricular function changes and its correlation with maximal exercise capacity in patients with chronic heart failure. For this purpose, a double blind crossover study was designed, and the change in the exercise tolerance and both ventricular ejection fraction were evaluated. When compared with digoxin treatment (p less than 0.01) and with a control-period (p less than 0.001), the captopril increases total exercise time significantly. The response of right ventricular ejection fraction was similar. The changes in right ventricular ejection fraction, but not those of left ventricular ejection fraction, correlated with the variations of exercise time (r = 0.67). These facts suggest that right ventricular function is an important determinant of exercise capacity in patients with chronic heart failure and that its behaviour explain, in part, the response to captopril treatment. PMID- 2185527 TI - Endotoxin concentrations in the blood following intravenous injection and effect on prostaglandin F2 alpha release, calcium and bile acids in goats. AB - Injection of endotoxin from Salmonella typhimurium in male goats resulted in a biphasic release pattern of PGF2 alpha, as determined by 15-ketodihydro-PGF2 alpha concentrations in plasma. A small initial peak at 30 minutes was followed by a second peak one hour after injection. The rectal temperature increased three to five hours after endotoxin injection and calcium concentrations started to decrease soon after injection; a significant decrease was seen from 105 minutes. Endotoxin concentrations varied among the animals but had a tendency to increase three hours after injection, simultaneously with a decrease in bile acid concentrations three hours after injection. The decrease in bile acids indicated alimentary stasis. Therefore, the raised endotoxin levels could be of endogenous origin. This study also shows that the prostaglandin metabolite is a very reliable parameter for estimating the effect of endotoxin. PMID- 2185528 TI - [What is your diagnosis? Alveolar upper lobe pneumonia]. PMID- 2185529 TI - [Hormone therapy in the 40-year-old woman]. AB - Hormone replacement therapy is frequently prescribed in 40-year old women because of the hormonal changes which start to occur at this age. A progestogen-only treatment is often prescribed to restore the oestrogen/progestogen balance. This treatment alone can be sufficient on the therapeutic level as well as on the contraceptive level. However, in order to minimize the risks of such a treatment, a non-androgenic derivative must be chosen. There are no contra-indications for oral contraceptives in women who are over 40 years old on condition that the risk factors are not cumulated. Here also, it is advisable to use the lowest possible dose of steroids which has an adequate contraceptive action and enables a good cycle control. As for oestrogens, the minimum ethinyloestradiol dose must be sought. For the progesterone dose, a non-androgenic derivative should be chosen. The GnRH agonists may have some indications, but their exact place is yet to be defined. PMID- 2185530 TI - [Lobular carcinoma in situ of the breast]. AB - The diagnosis of the lobular carcinoma in situ (LCIS), whose frequency is estimated to range from 0.8 to 3.8 p. cent of breast cancers on the whole, is exclusively anatomopathological since it does not have any specific clinical and/or radiological characteristics. After describing the two main differential diagnoses, the various possible treatments are studied, bearing in mind that the therapeutic strategy must take into account the three characteristics which are typical of LCIS: multicentricity, bilaterality and the possible occurrence of an invasive cancer. PMID- 2185531 TI - [Neonatal death following injuries in utero, in the absence of maternal lesions]. AB - The authors report a case of neonatal death at 24 hours following maternal trauma during a traffic accident. The abdominal trauma did not result in any maternal injury. Caesarean delivery was justified by fetal rhythm disorders. A wide variety of fetal injuries, in the absence of maternal injuries, are reported in the literature. Some benefit from an early diagnosis, improving therefore the fetal prognosis. PMID- 2185532 TI - The Nobel lectures in immunology. The Nobel Prize for Physiology or Medicine, 1913, awarded to Charles Richet. 'In recognition of his work on anaphylaxis'. PMID- 2185533 TI - In vivo and in vitro antibacterial activity of conglutinin, a mammalian plasma lectin. AB - Conglutinin is a mammalian C-type lectin which agglutinates iC3b-coated erythrocytes. Ingram [13] found that euglobulin from bovine serum may confer partial protection against experimental infections in mice. We now present evidence that the protective activity in euglobulin against infections of BALB/c mice with Salmonella typhimurium is mediated by conglutinin. Conglutinin also demonstrated antibacterial activity against E. coli and S. typhimurium in vitro. The expression of this activity required the presence of heat-labile serum factors and peritoneal exudate or spleen cells, but not antibodies to the bacteria. Antibacterial activity was also demonstrated when the bacteria were pretreated with serum at 37 degrees C before incubation with conglutinin and cells. The activity of conglutinin was not observed when factor I-deficient or EDTA-treated serum was used instead of normal serum. The active peritoneal exudate or spleen cells showed adherence to plastic. PMID- 2185534 TI - Quantitation of antibody-secreting cells in the blood after vaccination with Haemophilus influenzae type b conjugate vaccine. AB - The human B-lymphocyte response to protein-conjugated polysaccharide antigens has not previously been studied at the cellular level. In order to do so, we developed and evaluated haemolytic plaque-forming cell assays detecting Haemophilus influenzae type b (Hib) capsular polysaccharide-specific antibody secreting cells (AbSC) of the isotypes IgM, IgG, and IgA. The appearance of AbSC in the blood after vaccination of adults with diphtheria toxoid-conjugated Hib polysaccharide was investigated. AbSC were detected from post-vaccination day 5 to day 14. IgA was the predominant isotype among these cells. IgM AbSC peaked slightly earlier (median day 7) than IgG and IgA AbSC (both day 8). On post vaccination day 8 the numbers of AbSC were: IgA, 1217/10(6) mononuclear cells (median); IgG, 211; and IgM, 30 (n = 11). Similar isotype distribution has earlier been found after vaccination with pure capsular polysaccharides from Hib and pneumococci. The predominance of IgA AbSC in response to both conjugate and pure polysaccharide vaccines is probably due to reactivation of the same clones of IgA-committed memory B cells originally primed at the mucosa by natural exposure to the polysaccharide or cross-reacting antigens. PMID- 2185535 TI - Barriers to the care of persons with dual diagnoses: organizational and financing issues. AB - Among the frustrations of managing the dual disorders of chronic mental illness and alcohol and drug abuse is the fact that knowing what to do (by way of special programming) is insufficient to address the problem. The system problems are at least as intractable as the chronic illnesses themselves. Organizing and financing care of patients with comorbities is complicated. At issue are the ways in which we administer mental health and alcohol and drug treatment as well as finance that care. Separate administrative divisions and funding pools, while appropriate for political expediency, visibility, and administrative efficiency, have compounded the problems inherent in serving persons with multiple disabilities. Arbitrary service divisions and categorical boundaries at the State level prevent local governments and programs from organizing joint projects or creatively managing patients across service boundaries. When patients cannot adapt to the way services are organized, we risk reinforcing their overutilization of inpatient and emergency services, which are ineffective mechanisms for delivering the care these patients need. This article reviews the barriers in organization and financing of care (categoric and third party financing, including the special problem of diagnosis-related groups limitations) and proposes strategies to enhance the delivery of appropriate treatment. PMID- 2185536 TI - Acute effects of drug abuse in schizophrenic patients: clinical observations and patients' self-reports. AB - Substance abuse among schizophrenic patients is an increasingly recognized clinical phenomenon. The authors review experimental and observed clinical effects of drug abuse and patients' subjective experiences of acute intoxication. Though drug abuse may exacerbate psychotic symptoms, abused drugs may also lead to transient symptom reduction in subgroups of schizophrenic patients. Some patients report feeling less dysphoric, less anxious, and more energetic while intoxicated. Models of the relationship of drug abuse and schizophrenia, particularly the self-medication hypothesis, are discussed in reference to these data. PMID- 2185537 TI - Impact of substance abuse on the course and outcome of schizophrenia. AB - Numerous pharmacological agents have been shown to have powerful effects on cognitive behavior. Schizophrenia-like reactions have been reported in some instances. There have also been persistent reports of drug abuse among psychiatric patients before and during hospitalization. These phenomena have led to speculation that psychoactive substances are affecting the course and outcome of psychiatric illnesses, and in particular, schizophrenia. This report first reviews the evidence for psychotomimetic effects of various drugs, and then focuses on reports of the effect that substance abuse has on the course of schizophrenia and long-term outcome. The evidence to date indicates that there is a need for a large epidemiological analysis of the interplay between drug abuse and schizophrenia as well as more intensive case studies of afflicted individuals. This discussion concludes with suggestions for improved research methods and two designs for future investigations. PMID- 2185538 TI - Dopaminergic mechanisms in idiopathic and drug-induced psychoses. AB - Stimulant drugs such as cocaine and amphetamine are among the most commonly abused substances by schizophrenic patients. This may be due in part to aspects of the illness and treatment side effects that impel patients to use dopamine agonist drugs. Dopaminergic neural systems have been shown to mediate both stimulant drug effects and schizophrenia. Because of the hypothesized overlap in the pathophysiology of schizophrenia and the neurobiological effects of chronic stimulant use, the potential for serious complication of the primary disease by substance abuse exists. This article reviews the neurobiological mechanisms of behavioral sensitization and neurotoxicity associated with chronic stimulant administration in the context of pathophysiological theories of schizophrenia. Discussion focuses on the potential impact of stimulant use on the disease process as well as the manifest phenomenology and course of schizophrenia. PMID- 2185539 TI - Report of the International Committee on Nickel Carcinogenesis in Man. PMID- 2185540 TI - Second opinion. The heat is on Gallo--again. PMID- 2185541 TI - An RNA polymerase-binding protein that is required for communication between an enhancer and a promoter. AB - Although bacteriophage T4 late promoters are selectively recognized by Escherichia coli RNA polymerase bearing a single protein encoded by T4 gene 55 (gp55), efficient transcription at these promoters requires enhancement by the three T4 DNA polymerase accessory proteins, bound to distal "mobile enhancer" sites. Two principles are shown to govern this transcriptional enhancement: (i) Promoter recognition and communication between the enhancer and the promoter require separate phage-coded proteins. Only RNA polymerase that has the T4 gene 33 protein (gp33) bound to it is subject to enhancement by the three DNA replication proteins. (ii) Transcriptional enhancement in this prokaryotic system is promoter-specific. Promoter specificity is generated by a direct competition of phage T4 gp33 and gp55 with the E. coli promoter recognition protein, sigma 70, for binding to the E. coli RNA polymerase core. Thus, polymerase that contains sigma 70 is competent to transcribe T4 early and middle genes, but lacks the ability to be enhanced by the DNA replication proteins, while polymerase that contains gp55 and gp33 is capable of enhancement via gp33, but its activity is restricted to T4 late promoters by gp55. PMID- 2185542 TI - A Mn2(+)-dependent ribozyme. AB - An RNA hairpin identical in sequence with the one formed during autocyclization of the 414-nucleotide Tetrahymena intervening sequence undergoes strand scission at a specific site in the presence of Mn2+. In addition to representing one of the smallest and simplest ribozymes possible, strand scission occurs readily under physiological conditions, is unaffected by the presence of Mg2+, and displays salt, pH, and temperature optima of potential use in exploiting Mn2+ as a regulatory switch in intact cells. The chemistry of strand scission of the RNA hairpin is described, as is the Mn2(+)-dependent solvolysis of a 231-nucleotide RNA transcript containing this structural motif. PMID- 2185543 TI - L-cysteine, a bicarbonate-sensitive endogenous excitotoxin. AB - After systemic administration to immature rodents, L-cysteine destroys neurons in the cerebral cortex, hippocampus, thalamus, and striatum, but the underlying mechanism has never been clarified. This neurotoxicity of L-cysteine, in vitro or in vivo, has now been shown to be mediated primarily through the N-methyl-D aspartate subtype of glutamate receptor (with quisqualate receptor participation at higher concentrations). In addition, the excitotoxic potency of L-cysteine was substantially increased in the presence of physiological concentrations of bicarbonate ion. L-Cysteine is naturally present in the human brain and in the environment, and is much more powerful than beta-N-methylamino-L-alanine, a bicarbonate-dependent excitotoxin, which has been implicated in an adult neurodegenerative disorder endemic to Guam. Thus, the potential involvement of this common sulfur-containing amino acid in neurodegenerative processes affecting the central nervous system warrants consideration. PMID- 2185545 TI - Ifosfamide in the management of gynecologic cancers. AB - Ifosfamide, an alkylating agent chemically similar to cyclophosphamide, has been tested both as a single agent and in combination therapy for a variety of gynecologic cancers. In celomic epithelial carcinoma of the ovary, single agent ifosfamide yields response rates ranging from 19% to 79% and, most significantly, responses in patients who are refractory to cisplatin. Use in combination with both cisplatin and carboplatin has been reported, but the relative merits of these two combinations are indeterminate at present. In carcinoma of the cervix, response rates for ifosfamide alone range from 20% to 40% in patients who have not received prior chemotherapy. Very high response rates from 67% to 86% have been reported with ifosfamide in combination with platinum compounds with or without other agents such as doxorubicin and bleomycin. No studies have yet demonstrated superiority of combination therapy. Data from the Gynecologic Oncology Group demonstrate activity for ifosfamide alone in mixed mesodermal sarcomas of the uterus. Finally, anecdotal data note responses in endometrial carcinoma and germ cell carcinomas of the ovary. Thus, it appears that ifosfamide has significant activity in a variety of gynecologic cancers and deserves further testing as a part of combination chemotherapy in at least celomic epithelial carcinomas of the ovary, cervix carcinomas, and mixed mesodermal sarcomas of the uterus. PMID- 2185544 TI - The staphylococcal enterotoxins and their relatives. AB - Staphylococcal enterotoxins and a group of related proteins made by Streptococci cause food poisoning and shock in man and animals. These proteins share an ability to bind to human and mouse major histocompatibility complex proteins. The complex ligand so formed has specificity for a particular part of T cell receptors, V beta, and by engaging V beta can stimulate many T cells. It is likely that some or all of the pathological effects of these toxins are caused by their ability to activate quickly so many T cells. It is also possible that encounters with such toxins have caused mice, at least, to evolve mechanisms for varying their T cell V beta repertoires, such that they are less susceptible to attack by the toxins. PMID- 2185546 TI - Ifosfamide studies for primary or recurrent pediatric malignant solid tumors and leukemia. AB - Ongoing studies using ifosfamide with mesna for primary or recurrent pediatric malignancies are reviewed. These studies include evaluations of ifosfamide given before conventional agents, in combination with other agents, with other effective agents and radiation therapy, and in alternative schedules. PMID- 2185548 TI - Pathophysiology of cancer-associated hypercalcemia. AB - During the past decade, specific mediators of bone destruction in hypercalcemia of malignancy have been identified and characterized. These humoral factors include parathyroid hormone-related protein, transforming growth factor alpha, and cytokines such as interleukin-1 and tumor necrosis factor. In metastatic hypercalcemia associated with breast cancer, prostaglandin secretion by tumor cells may be one of the important factors. Among the osteoclast activating factors associated with hypercalcemia in patients with myeloma, lymphotoxin plays a central but probably not exclusive role. Alterations of renal function in hematologic hypercalcemia may potentiate bone destruction that usually occurs in the presence of impaired rates of glomerular filtration. Further research is required to determine the relative contributions of bone and kidney to the pathogenesis of hypercalcemia of malignancy. PMID- 2185547 TI - The role of ifosfamide in the treatment of adult soft tissue sarcomas, Ewing's sarcoma, and osteosarcoma: a review. AB - Ifosfamide is an analogue of cyclophosphamide that has been extensively investigated in sarcomas. Like doxorubicin and dacarbazine, it belongs to the class of drugs active against advanced soft tissue sarcomas; its optimal use in combination regimens has not been identified. In the treatment of osteosarcoma and Ewing's sarcoma, ifosfamide has been identified as an effective drug. Nonetheless, in these diseases, too, its optimal place in combination therapy has not yet been determined. PMID- 2185549 TI - Clinical manifestations of cancer-related hypercalcemia. AB - Hypercalcemia is a potentially lethal endocrine disorder occurring in 10% to 20% of cancer patients at some time during the course of their disease. Clinical manifestations vary in severity, depending on the degree and duration of hypercalcemia, rapidity of onset, patient's age, performance status, sites of metastases, previous antineoplastic therapy, and the presence of hepatic or renal dysfunction. The clinical features of hypercalcemia are protean and affect multiple organ systems, resulting most prominently in neurologic, gastrointestinal, renal, cardiovascular, and musculoskeletal morbidity. Recognition of the disorder requires a high index of suspicion because many of its symptoms, such as nausea, anorexia, weakness, fatigue, lethargy, and confusion, are non-specific and, in the patient with a malignancy, can result from other complications of the primary disorder. If identified appropriately as being related to hypercalcemia, such symptomatology is potentially reversible with treatment. Whereas in the ambulatory general medical population the most common cause of hypercalcemia is primary hyperparathyroidism, in cancer patients and hospitalized patients in general, the most common cause is malignancy. Hypercalcemia in cancer patients is, in most cases, due to advanced metastasized disease. Diagnostic tests are useful in the differential diagnosis of hypercalcemia, and such tests, together with an accurate history and careful clinical observation, permit the best therapeutic approach to an individual patient. PMID- 2185550 TI - Treatment of cancer-related hypercalcemia. AB - Hypercalcemia, a complication that develops in 10% to 20% of patients with cancer, results from disruption of the normal physiologic mechanisms that closely regulate calcium homeostasis. Most patients with hypercalcemia are seriously dehydrated, and this volume depletion further compromises the kidney's ability to excrete calcium. Replenishment of extracellular fluid, restoration of intravascular volume, and maintenance of saline diuresis are the cornerstones of initial therapy. In most patients, pharmacologic inhibition of abnormally increased osteoclastic resorption is necessary to normalize serum calcium and achieve long-term control. The severity of the hypercalcemia and the patient's renal function, bone marrow reserve, and anticipated response to specific antineoplastic agents can all influence the selection of an antihypercalcemic agent. Available drugs for initial therapy include calcitonin, plicamycin, and etidronate; several additional investigational agents have shown promising efficacy in controlling hypercalcemia of malignancy. The bisphosphonates have an excellent safety profile and appear to be the agents of choice for initial and long-term management of cancer-related hypercalcemia. PMID- 2185551 TI - Overview of cancer-related hypercalcemia: epidemiology and etiology. AB - Hypercalcemia is one of the most serious metabolic disorders associated with cancer. The incidence and clinical circumstances associated with hypercalcemia vary in different types of cancer. Hypercalcemia is the most frequent metabolic complication of breast cancer and is usually related to widespread osteolytic metastases; however, local and systemic humoral factors mediating bone resorption have been described. In some patients with breast cancer, hypercalcemia results from treatment with estrogens, antiestrogens, androgens, or progestins. Coexisting primary hyperparathyroidism rarely confounds the diagnosis. In patients with lung cancer, the incidence of hypercalcemia varies with histology and is often unrelated to bone metastases. Hypercalcemia may occur either late or early in the disease but is seldom a presenting symptom. In patients with cancers of the head and neck region, hypercalcemia is most often associated with advanced recurrent and terminal disease, presumably humorally mediated. In renal cell carcinoma, hypercalcemia is also an adverse prognostic indicator, commonly mediated by humoral factors. On the other hand, almost all patients with multiple myeloma have extensive osteolytic bone destruction and hypercalcemia is frequently a presenting symptom. Hypercalcemia is uncommon in most lymphomas; however, it is usually a prominent feature of adult T-cell lymphomas and also occurs in some large cell, diffuse B-cell lymphomas. Awareness of the setting in which hypercalcemia of malignancy occurs will lead to its prompt diagnosis and institution of appropriate therapy. PMID- 2185552 TI - The mega shot. PMID- 2185553 TI - Traumatic posterior dislocation of the hip--a local experience and review of the literature. AB - The results of 30 patients who sustained traumatic posterior dislocation of the hip treated in both Departments of Orthopaedic Surgery in the Singapore General Hospital from January 1980 to May 1987 were analysed. The most common cause was motorcycle accidents. Young adult males formed the majority of affected cases. 90% of the dislocations were of the Types I and II. Associated injuries were common. The primary treatment was closed reduction under anaesthesia. The subsequent period of traction and non-weight bearing was variable, but it did not seem to affect the final results. Avascular necrosis of the femoral head and secondary osteoarthritis were the major complications. The overall functional results were good. PMID- 2185554 TI - Neonatology in Singapore. AB - A short account of the history of Neonatology in Singapore is given. Current practice and results of management of neonates are highlighted and future directions for neonatology in Singapore outlined. Brief mention is made of 2 common controversies in neonatal practice. PMID- 2185555 TI - Splenic lymphoma with hypersplenism--a case report. AB - A 47-year old man had hypersplenism from massive splenomegaly, the cause of which was undetermined for 2 years. He was initially asymptomatic though there was mild pancytopenia. However, 18 months after presentation he manifested both clinical and haematological deterioration, almost succumbing to sepsis. Splenectomy finally provided a definite diagnosis of follicular lymphoma and also restored his blood counts to within normal range. PMID- 2185557 TI - [Use of computers for improving the activities of health facilities at industrial plants]. AB - The organizational and methodological aspects of computer application at treatment facilities serving the industrial enterprises are described. Some conceptions of operating the automated centre of mass medical examinations at Novomoskovsk tube plant are outlined. A methodological approach is suggested: the use of computer systems according to the number of industrial workers. Considerable reserves of improving the performance of treatment facilities serving the workers and employees of industrial enterprises are pointed out. PMID- 2185556 TI - Scintigraphic evaluation of tumor regression during preoperative chemotherapy of osteosarcoma. Correlation of 99mTc-methylene diphosphonate parametric imaging with surgical histopathology. AB - The effect of preoperative chemotherapy (PCT) on the uptake of 99mTc-labeled diphosphonates into tumor bone was quantitatively assessed from serial scan studies of 30 osteosarcomas and correlated with the histomorphological changes determined from the surgical specimens. The parametric images of the tumor blood pool and labeled methylene diphosphonate (99mTc-MDP) plasma clearance by the tumor bone enabled a sensitive distinction to be made preoperatively between a good (greater than 90% tumor cell destruction) and a poor (less than 90% tumor cell destruction) tumor response. Overall accuracy in presurgical prediction of tumor regression was found to be 88% and 96% for the blood pool and 99mTc-MDP clearance measurements, respectively (P less than or equal to 0.0004). In addition, it proved possible to localize resisting areas of viable tumor up to 1.0 cm in diameter. Even at the half-way stage of PCT, a poor response could be reliably predicted (overall accuracy 91% and 100%, respectively; P less than or equal to 0.011). Therefore, 99mTc-MDP parametric imaging is a highly sensitive and specific modality for an objective and accurate assessment of tumor regression during PCT of osteosarcoma. PMID- 2185558 TI - [Use of computers in the training of medical students in medical statistics]. PMID- 2185559 TI - [The first provisional military hospital in Russia (1608-1612)]. PMID- 2185560 TI - [Development of obstetrics in Russia in the first half of the 19th century]. PMID- 2185561 TI - [Views of physicians in Zemskie on the role of education of the population in the health education of peasants]. PMID- 2185562 TI - [The English physician August Botsy Granville on the state of medicine in St. Petersburg]. PMID- 2185563 TI - [Acute promyelocytic leukemias: clinico-biological aspects, prognostic factors, therapeutic response, and possibilities of cure in 34 cases (1970-1988)]. AB - Thirty-four new cases of acute promyelocytic leukaemia (M3) were diagnosed at the authors' Centre between 1970 and 1988 (19 males and 15 females) with ages between 5 and 73 years (median age, 32 years). Three cases were of the hypogranular variant or M3-v (8.8%). The clinical picture included: haemorrhagic diathesis (85%), pallor/malaise (82%), fever/infection (41%), hepatomegaly (26%), splenomegaly (12%). Leucopenia of less than 5 x 10(9)/L was present in 23/34 cases, laboratory signs of DIC in 26/31, increased LDH, over 400 U/mL, in 6/31, and abnormal karyotype in 7/15. One of the patients rejected any treatment; two others died of brain haemorrhage before therapy was started, and seven died in the first two weeks of treatment. Of the 31 patients treated, complete remission (CR) was achieved in 21 cases (67.7%). Allogeneic BMT was carried out in two of them, with further relapse and death. Post-remission treatment was given to the remaining 19 patients, and there were 13 relapses. Six patients have been in CR, 5 of them after cessation of therapy, for the last 1.5-11.5 years. Age under 50 years and leucocyte count below 5 x 10(9)/L at diagnosis were favourable prognostic factors according to the univariate statistical analysis performed. The survival plateau of the actuarial curve was reached beyond 2.75 years by 15% of all the patients treated (33 cases), 23% of the patients who achieved CR (21 cases), 31% of the patients under 50 years of age and 5 x 10(9)/L leucocyte count at diagnosis (15 cases) and 36% of these last achieving CR (13 cases). PMID- 2185564 TI - [Primary lymphoproliferative processes of the gastrointestinal tract. A spectrum of clinico-biological phenotypes]. PMID- 2185565 TI - [The Antonio Raichs memorial lecture. Future trends in marrow transplantation]. PMID- 2185566 TI - New concepts of pathophysiology and treatment of portal hypertension. PMID- 2185567 TI - Coverage of full-thickness burns with bilayered skin equivalents: a preliminary clinical trial. AB - A total of six patients have received bilayered skin-equivalent coverage of full thickness burns, with takes of 50% to 70% in the later patients. These skin equivalent grafts are constructed by combining allogeneic fibroblasts with collagen to form a sheet and adding a suspension of autologous epidermal cells to the surface of the collagen matrix. These bilayered skin-equivalent grafts have provided an expansion of at least fifteenfold to twentyfold for the area covered by the donor epidermis. By 8 months after grafting, the skin-equivalent grafts appeared smooth and approximated the color of normal skin. Long-term problems associated with hypertrophic scarring or graft fragility have not developed during the 18-month period of follow-up. PMID- 2185568 TI - The hepatotropic influence of cyclosporine. AB - The effect of cyclosporine on liver regeneration has been investigated in 25 dogs that underwent an end-to-side portacaval shunt (Eck fistula) followed by 4 days continuous infusion of the drug into the left branch of the portal vein. Three different cyclosporine infusion rates were used: 0.06, 0.6, and 4.0 mg/kg/day. Control animals received the intravenous vehicle of cyclosporine at the same rate as the treated animals; a second control group received insulin, 0.42 units/kg/day. Hepatocyte 3H-thymidine-labeled mitoses (index of hyperplasia) and hepatocyte volume (index of hypertrophy) were studied in the left (infused) and right (control) lobes in each animal. Cyclosporine vehicle had no measurable effect on hepatocytes that suffered typical atrophy and moderate increase in mitotic index after the Eck fistula. Cyclosporine infusion stimulated cell renewal significantly and restored hepatocyte size in the infused lobes with a dose-response relation. Similar positive effects were observed in the right (nonperfused) lobes, although they were less than those in the left (infused) lobes. This was because of an unmistakable spillover of cyclosporine from the infused lobes, especially in the large-dose group. No sign of hepatotoxicity was detected at any cyclosporine infusion rate. Cyclosporine has a remarkable hepatotropic effect that may be helpful in the context of liver transplantation. PMID- 2185569 TI - Vitamin E and benign breast disease. AB - Vitamin E has been used in the treatment of benign breast disease for 25 years. To evaluate the efficacy of treatment by means of mammography as the objective and sensitive parameter, 105 women were randomly selected and entered into a double-blind, placebo-controlled crossover trial. All patients had mammographic evidence of benign breast disease. They received 600 mg of placebo and alpha tocopherol acetate in 3-month treatment phases. Breast examinations and mammography were done, after each treatment, at approximately the same phase of the patients menstrual cycle. No significant subjective or objective effects after treatment were observed. We conclude that alpha-tocopherol is not beneficial in the treatment of benign breast disease. We would warn against the use of alpha-tocopherol for misdirected treatment of undiagnosed overt disease because such treatment may delay the diagnosis of breast cancer. PMID- 2185570 TI - Fatal gastric artery dissection and rupture occurring as a paraesophageal mass: a case report and literature review. AB - Gastric artery aneurysms are rare, and the majority occur as life-threatening hemorrhage with few premonitory signs or symptoms. We report an unusual hemorrhagic manifestation of a ruptured gastric artery aneurysm, occurring as a pleural effusion and an apparent paraesophageal mass. Acute intraperitoneal and mediastinal bleeding from the extravisceral portion of the left gastric artery resulted in hemorrhagic shock, prompting an emergency laparotomy. Extensive medial degeneration in the gastric artery probably contributed to dissection and rupture. PMID- 2185571 TI - [Bullous pulmonary emphysema]. PMID- 2185572 TI - [Diabetes mellitus and the transport function of glycosylated and nonglycosylated albumin]. PMID- 2185573 TI - [The side effects of amiodarone on thyroid function]. PMID- 2185574 TI - [The comparative effectiveness of different psychological methods for treating patients with a labile course of hypertension (based on international research data)]. AB - Examination of 110 patients with essential hypertension (EH) carried out in the USSR and GDR revealed, by the end of the observation period (one year), a significant lowering and normalization of arterial pressure at rest and a certain reduction of the intensity of the hypertensive response to psychoemotional stress influences in the presence of psychological relaxation therapy (PRT). The survey made it possible to try the designed methods for PRT in both countries and demonstrated that the intensity of the hypotensive action of the methods appeared comparable in different populations of patients suffering from essential hypertension. The intensity of the hypotensive action of PRT correlated with the level of arterial pressure before treatment, with the age of EH patients, and with their psychological characteristics. PMID- 2185575 TI - [The use of metoprolol with calcium antagonists of different mechanisms of action (diltiazem and nifedipine) in patients with stenocardia of effort]. AB - The use of metoprolol combined with nifedipine and diltiazem was studied and compared in 32 patients suffering from coronary disease associated with angina pectoris of effort. The drug combinations indicated appeared equally effective in patients with angina pectoris, functional class III. In patients with angina pectoris of effort, functional classes III-IV, the combined use of metoprolol and diltiazem turned out superior as compared with nifedipine which is related to different hemodynamic effects of the drugs. PMID- 2185576 TI - [The initial experience of using pulse therapy with cyclophosphane and 6 methylprednisolone in patients with acute and subacute stages of nonspecific aortoarteritis]. AB - The authors summarize the first experience gained with the use of pulse therapy with cyclophosphamide and 6-methylprednisolone in 18 patients with acute and subacute nonspecific aortoarteritis. Remission attained in 16 patients was attended by a decrease in objective criteria of the process acuity. It has been noted that duration of the remission was inversely proportional to the time of the inflammatory anamnesis. Provided the patients manifested exacerbation of the process, repeated courses of pulse therapy were conducted. PMID- 2185577 TI - Nephrotic syndrome associated with ant bite. AB - A 3-year-old child experienced edema of the face and extremities approximately 2 weeks after being stung on the legs, scrotum, and penis by "fire ants" (Solenopsis invicta). After diagnosis of idiopathic minimal-change nephrotic syndrome and treatment with steroids, the edema rapidly disappeared. Follow-up 3 years after his hospitalization showed no recurrence of nephrotic syndrome. We have correlated this case with previously published reports of the causal relationship of allergy to nephrotic syndrome, but we are unaware of any previously published correlation between ant bite and nephrotic syndrome. PMID- 2185578 TI - Prenatal laboratory screening. AB - Expectations of the clinician are evolving in obstetric practice in regard to standards of performance, cost effectiveness, and outcomes for mother and child. Prenatal laboratory screening is shown to be an area where new developments are evident. The purpose of this article is to update information found in standard obstetrics textbooks. PMID- 2185579 TI - Waivers of insurance deductibles--charity or crime? AB - Many physicians occasionally waive insurance deductibles and copayments for their patients. Some do it routinely and advertise the fact. Aetna Life Insurance Company in 1988 called this practice fraud, a position The National Health Care Anti-Fraud Association subsequently took (1). However, it is all too easy to apply that label without analyzing the facts. This article examines the practice of waiving copayments and deductibles, describes recent developments in the area, and offers some guidelines for physicians. PMID- 2185580 TI - [Endoscopic retrograde cholangio-pancreatography in suspected acute gallstone pancreatitis]. AB - During the 5-year-period from July 1983 to July 1988, ERCP was performed within 48 hours after onset of clinical symptoms in 63 patients with suspected gallstone pancreatitis. In 53 patients this etiology was confirmed, and acute endoscopic papillotomy was done in 30 of these patients. ERCP seems to be a safe diagnostic procedure in acute gallstone pancreatitis, and papillotomy gives effective drainage and relief of the acute symptoms. PMID- 2185581 TI - [Disulfiram and calcium carbimide. Mode of action, adverse effects and clinical use]. AB - The alcohol-sensitizing drugs disulfiram and calcium carbimide are often used in the treatment of alcohol problems with the hope of reducing alcohol consumption. These drugs inhibit the liver enzyme acetaldehyde dehydrogenase and, when taken prior to ethanol, produce an acetaldehyde-mediated aversive reaction. However, the drugs are unspecific, and several side effects may be related to their influence on other biochemical processes. These drugs are primarily pharmacological adjuncts and should be used in conjunction with behavioural and psychosocial therapies. PMID- 2185582 TI - [Disulfiram implants. Lack of pharmacological and clinical effects]. AB - The therapeutic rationale for using implanted disulfiram is possible inhibition of the liver enzyme acetaldehyde dehydrogenase, producing an acetaldehyde mediated aversive reaction after intake of ethanol. Several studies using volunteers and patients in a double blind controlled study produced no evidence that a disulfiram implant (1 g) has any significant pharmacological or clinical action, except for a higher frequency of local surgical complications. PMID- 2185583 TI - [Clinical investigation of suspected streptococcal disease. Gambling or rational methods?]. PMID- 2185584 TI - Metabolites of testosterone: significance in the vital economy. AB - Testosterone is metabolized by practically every tissue in the body to a large variety of related steroids. The metabolites vary with each tissue and appear to be formed to meet the specific needs of the particular tissue and animal. The many biologic actions of testosterone do not change in parallel in the various metabolites. Many of the metabolites show interesting differences in their relative biologic effects. A large number and variety of steroid-metabolizing enzymes (oxidoreductases, reductases, hydroxylases, aromatases) are involved. Some have been partially purified. The 17 beta-oxidoreductases of the cytosol of the guinea pig liver and kidney have been purified and characterized. PMID- 2185585 TI - Differential expression of carcinoembryonic antigens and non cross-reacting antigens in the human thymus. Analysis on frozen sections and cultured epithelial cells using monoclonal antibodies. AB - The organization of epithelial cells in distinct areas of the thymus appears important for understanding the pathways of T-cell differentiation. The presence of carcinoembryonic antigen (CEA) was investigated on sections of human thymus and in cultures of thymic epithelial cells through use of monoclonal antibodies (Mab) discriminating CEA and 2 non cross-reacting antigens (NCA 55 and NCA 95). All together, 5 monoclonal antibodies were used. The Mab 35 and 73 recognized exclusively a specific CEA antigenic determinant, whereas Mab 47, 192 and 202 were also reactive with CEA cross-reacting antigens. By immunofluorescence or the immunoperoxidase technique, staining of CEA was restricted essentially to Hassall's corpuscles and a few adjacent epithelial cells on thymic sections; this pattern was similar to distribution of Ca 19-9 antigen. Additionally, the 47, 192 and 202 antibodies were reactive with a keratin-negative subset mainly located in the cortex. Furthermore, a subset of keratin-positive cells bearing CEA molecules was observed in thymic epithelial cell cultures. Positive cells comprised less than 3% with Mab 35 and 73, and reached up to 12% with Mab 47, 192 and 202. By flow cytometry analysis, staining intensity varied with the epitope; it was much weaker with Mab 35, 47 and 73 than with Mab 192 and 202. The CEA content in culture supernatants was inversely correlated to the number of CEA positive cells. Thus, CEA could be considered as a marker of a late maturation stage of medullary epithelial cells culminating in Hassall's corpuscles and could contribute to delineating the heterogeneity of thymic epithelial cells. PMID- 2185586 TI - Developing selective inhibitors of calpain. PMID- 2185587 TI - Free radicals and ischemic tissue injury. AB - There is growing evidence that reperfusion of ischemic organs is associated with the formation of free radicals that exacerbate the ischemic injury. Free radicals may damage viable tissue via the peroxidation of lipids and oxidation of protein sulfhydryl groups, leading to perturbations of membrane permeability and enzyme function. Steven Werns and Benedict Lucchesi discuss evidence that activated neutrophils are an important source of free radicals after cardiac and intestinal ischemia, and assess the strategies that have been investigated as ways of alleviating damage caused by free radicals during ischemia-reperfusion. PMID- 2185588 TI - Xanthogranulomatous pyelonephritis in children: analysis by diagnostic modalities. AB - Xanthogranulomatous pyelonephritis (XGP), an uncommon chronic inflammatory renal disorder of middle-aged women, is rarely seen in childhood. We report the sonographic findings in a 2-year-old girl with the diffuse form of XGP and discuss the role of newer imaging modalities in the diagnosis and management of this disorder. PMID- 2185589 TI - Condylomata acuminata of the bladder: a rare cause of intraluminal-filling defects. AB - Condylomata acuminata is a sexually transmitted disease commonly affecting the mucocutaneous surfaces of the anogenital region. Extension to the bladder is exceedingly rare. We present a case of condylomata acuminata causing intraluminal filling defects of the bladder in a patient being evaluated for chronic urinary tract infections. PMID- 2185590 TI - Mullerian duct cyst: ultrasonographic and computed tomographic spectrum. AB - A Mullerian duct cyst (MDC) is the persistent remnant of the Mullerian duct. Reports of symptomatic cases are rare, signs and symptoms include perineal pain, dysuria, infertility, hematuria and genital inflammation. The prevalence of MDC has been previously reported as 4% of newborns and 1% in adult males. Herein we report six cases encountered in the past year. Our detection percentage was 1% and is compatible with the reported values. The imaging evaluation of symptomatic and asymptomatic patients with MDC is discussed as well as the apparent discrepancy between the number of previously reported cases and the reported prevalence. PMID- 2185591 TI - Intraoperative real-time ultrasonic scanning for microwave coagulation of the prostate. AB - Nine patients with severe dysuria caused by prostatic cancer received prostatic microwave coagulation under intraoperative real-time ultrasonic scanning. During the procedure, the microwave applicator was clearly observed, and the coagulation region appeared as an hyperechoic area compared to the noncoagulated region. Intraoperative real-time ultrasonic scanning allowed safer and more efficacious application of prostatic microwave coagulation. PMID- 2185592 TI - Tuberculous abscess of the testicle in AIDS: sonographic demonstration. AB - A patient with acquired immune deficiency syndrome (AIDS) who presented with right testicular swelling is described. Sonography demonstrated diffuse enlargement and inhomogeneity of the testicle with central hypoechoic areas. Testicular abscesses were seen at surgery and Mycobacterium tuberculosis was cultured from the surgical specimen. Tuberculosis should be considered in the differential diagnosis of testicular enlargement or abscess formation in AIDS. PMID- 2185593 TI - [Use of sorbents of cesium and strontium for internal decontamination of animals]. PMID- 2185594 TI - Mechanical properties of four suture patterns for transected equine tendon repair. AB - Thirty-six superficial digital flexor tendons from nine fresh equine cadavers were transected and sutured with size 2 monofilament nylon. Nine tendons were repaired with each of four suture patterns: single-locking loop, double-locking loop, triple-locking loop, or three-loop pulley. The times required for application, tensile strengths, resistance to distraction (gap), and modes of failure were analyzed. The mean times required were: single-locking loop, 3 mins, 15 secs; double-locking loop, 4 mins, 15 secs; triple-locking loop, 10 mins, 50 secs; and three-loop pulley, 4 mins. The double-locking loop, triple-locking loop, and three-loop pulley suture patterns were stronger than the single-locking loop. The triple-locking loop and three-loop pulley patterns were close in strength and only the triple-locking loop was stronger than the double-locking loop. The three-loop pulley had the greatest resistance to gap formation and its mode of failure was different from the others. The three-locking loop suture patterns failed by suture breakage but the three-loop pulley failed first by suture pull-out and then by suture breakage. PMID- 2185595 TI - The efficacy of cervical cerclage. AB - A retrospective study of the outcome of pregnancy in 187 women with cervical cerclage revealed a three-fold increase in the crude perinatal survival rate. The McDonald and Shirodkar techniques produced comparable results. Mersilene was as effective as black silk. A significant number of pregnancies with cerclage insertion prior to 14 weeks ended in spontaneous abortions. Postcerclage morbidity was minimal, and abdominal delivery was indicated in only four patients for cervical dystocia. The continued use of this procedure, for selected cases, is justified. PMID- 2185596 TI - Dengue fever in the Caribbean. PMID- 2185597 TI - Syndrome of plasma cell dyscrasia, polyneuropathy, and diabetes mellitus. AB - Multiple myeloma associated with sclerotic bone lesions and polyneuropathy represents a distinct subset of the plasma cell dyscrasias. We describe a case of biclonal gammopathy (the second case reported), insulin-resistant diabetes mellitus, and no evidence for anti-insulin receptor antibodies. After treatment with chemotherapy and irradiation, the diabetes resolved, the polyneuropathy lessened greatly, and the patient is alive without evidence of progression five years later. The reports of 95 other cases are reviewed. This syndrome occurs in younger patients (mean age, 48 years) and is frequently associated with organomegaly, endocrinopathies, and skin changes. Irradiation to the sclerotic bone lesions frequently lessens the neuropathy and endocrinopathies and may result in long-term remission. The mechanism of action leading to the systemic effects seen in this syndrome is unknown but is likely related to proteins secreted by the abnormal plasma cells. PMID- 2185598 TI - Physician payment reform--an idea whose time has come. AB - These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from transcriptions, they are prepared by Homer A. Boushey, MD, Professor of Medicine, and Nathan M. Bass, MD, PhD, Associate Professor of Medicine, under the direction of Lloyd H. Smith, Jr, MD, Professor of Medicine and Associate Dean in the School of Medicine. Requests for reprints should be sent to the Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA 94143. PMID- 2185599 TI - [Behavior analysis of eating disorders]. AB - Modification of behavior is based on an analysis of behavior. An investigation of behavioral disturbances with respect to conditions, trigger mechanisms, causes, as well as functions and effects on the patient is necessary. PMID- 2185600 TI - [The toxicological estimation of the heavy metal content (Cd, Hg, Pb) in food for infants and small children]. AB - There are differences between young and adult organisms regarding toxokinetic aspects and clinical manifestations of heavy metal intoxications. Chronically, toxic Cd intake causes a microcytotic hypochromic anemia in young rats at lower exposure levels and after shorter exposure periods than in adult animals. Cd absorption is increased by co-administration of milk and in conjunction with iron deficiency. After long exposure periods toxic Cd concentrations accumulate in the kidney cortex; this process starts very early in life. In 3-year-old children Cd concentrations in the kidney can reach up to one-third of those found in adults. Hg++ and methyl-Hg can cause Hg encephalopathia, and frequently cause mental retardation in adults. Correspondingly, Hg++ accumulation in the brains of suckling rats is approx. 10 times higher than in grown animals. Milk increases the bioavailability of Hg++. In suckling rats Hg is bound to a greater extent to ligands in the erythrocytes. Methyl-Hg concentrations in breast milk reach 5% of those in maternal plasma and that is a severe hazard for breastfed children of exposed mothers. Toxic Pb concentrations can lead to Pb encephalopathia. A high percentage of surviving children have seizures and show signs of mental retardation. Anemia and reduced intelligence scores were recently observed in children after exposure to very low levels of Pb. Pb absorption is increased in children and after co-administration of milk. There are no definite proofs for carcinogenesis or mutagenesis after oral exposure to Cd, Hg, and Pb in man. Heavy metal concentrations were found in the same order of magnitude in commercial infant formulas and in breast milk. When infant formulas are reconstituted with contaminated tap water, however, Pb and Cd concentrations can be much higher. The average heavy metal uptake from such diets exceeds the provisional tolerable weekly intake levels set by the WHO for adults, calculated on the basis of an average food intake and a downscaled body weight. These considerations do not even provide for differences in absorption and distribution or for the increased sensitivity of children to heavy metal exposure. However, dilution effects for essential heavy metals were observed in fast-growing young children; this effect might be extrapolated to toxic metals. These theoretical considerations are compared with epidemiological evidence. A health statistic from Baltimore shows a decline of Pb intoxications in infants. This observation correlates with a simultaneous decline in exposure to Pb which was due, for example, to decreased use of lead dyes in house paints and the abolition of tin cans for infant food.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2185601 TI - [Guillaume Dupuytren--1777-1835]. PMID- 2185602 TI - Neurohypophysial secretion to insulin-induced hypoglycemia and its regulation by endogenous opioids in women. AB - In animals, there is sexual dimorphism of both neurohypophysial peptide secretion in response to stressful stimuli and to the inhibitory effects of opioids. In men, endogenous opioids inhibit the release of oxytocin when AVP secretion is stimulated by insulin-induced hypoglycemia. We have now investigated the role of endogenous opioids in the AVP and oxytocin response to insulin-induced hypoglycemia in women. Twelve subjects, 6 in the follicular and 6 in the luteal phase of the menstrual cycle, were infused on 2 occasions with naloxone (4 mg bolus and 6 mg/h) or saline. Soluble insulin (Human Actrapid, 0.15 mu/kg, iv) was given and serial blood samples taken. Blood sugar fell significantly (p less than 0.05) and similarly in all groups. In the follicular phase hypoglycemia led to a rise in plasma AVP from 1.3 +/- 0.2 to 1.8 +/- 0.2 pmol/l in the saline-infused subjects (NS), and from 1.0 +/- 0.1 to 2.0 +/- 0.2 pmol/l in the naloxone-infused (p less than 0.05). AVP rose similarly from 0.6 +/- 0.1 to 1.6 +/- 0.5 pmol/l (p less than 0.05) in the luteal phase controls and from 0.8 +/- 0.1 to 1.5 +/- 0.3 pmol/l (p less than 0.05) in naloxone-infused subjects in the luteal phase. There were no significant differences between any of these groups. There were no significant changes in plasma oxytocin in any group. We therefore conclude that in women, unlike men, endogenous opioids do not modulate oxytocin or vasopressin release during insulin-induced hypoglycemia. PMID- 2185603 TI - Renal calcium and magnesium handling in experimental diabetes mellitus in the rat. AB - Metabolic and renal clearance techniques were used to examine kidney function in conscious and anesthetised streptozotocin diabetic rats. All diabetics showed an enhanced calcium and magnesium excretion compared to controls. However, the renal handling of these ions in relation to other electrolytes varied with different experiments. In non-infused conscious rats, the excretion of all ions was higher in diabetics, but the increased output of Ca2+ and Mg2+ was far greater than that of other electrolytes. In infused anesthetised diabetics only the outputs of Ca2+ and Mg2+ were significantly raised. This resulted from a significant reduction in the tubular reabsorption of both ions (% Ca2+ reabsorption: Controls 97.0 +/- 0.5; Diabetics 86.1 +/- 2.1; p less than 0.001). Insulin treatment reversed these changes. Major differences therefore exist in the renal handling of Ca2+ and Mg2+ in control and diabetic kidneys. Such differences do not simply parallel changes in the handling of other ions, and thus represent specific Ca2+ and Mg2+ lesions. Anesthetised infused diabetic rats also showed a reduced glomerular filtration rate and urine output compared to controls. Such differences may relate to an altered fluid balance in the two groups, different responses to surgery and anesthesia, or the degree of hyperglycemia in diabetic animals. PMID- 2185604 TI - Glucagon and insulin secretion in low birthweight preterm infants. The effect of glucose infusion. AB - The effect of the intravenous glucose on plasma levels of glucagon and insulin were evaluated in thirty-five LBW preterm infants who were appropriate for gestational age. Their mean birthweight and gestational age were 1220 +/- 55 g (range 750-1730 g) and 29 +/- 1 weeks (range 25-35 weeks), respectively. A 30 min glucose infusion in 16 infants (1 g/kg b.w. in 30 min) caused a prompt and sustained suppression of plasma glucagon and a delayed but significant insulin release. The mean of the sum of maximal plasma glucagon decrements below the baseline was 173 +/- 42 pg/ml. In another 12 infants a significant fall in plasma glucagon and a variable but significant plasma insulin release also occurred throughout the 24 h study on continuous intravenous glucose (rate 2.4-2.7 mg/kg/min). The mean of the sum of maximal plasma glucagon decrements below the baseline up to 12 h was 282 +/- 36 and was similar to that seen in the previous group. PMID- 2185605 TI - Insulin cord levels in large for gestational age infants born to non-obese, non diabetic mothers. PMID- 2185606 TI - Movement disorders and new azapirone anxiolytic drugs. AB - Dopamine is a neurotransmitter affecting motor function, and the dopamine system is the focus of abnormality in dyskinetic diseases. An important side effect of many psychotropic drugs possessing dopamine activity is the production of movement disorders; this potential problem needs to be examined carefully with any new central nervous system drug, such as the azapirone anxiolytic drugs. The pharmacology of the azapirones, represented by the prototype, buspirone, involves several different neuroreceptor systems. Current evidence indicates that buspirone's anxiolytic activity is mediated through serotonergic mechanisms. It also displays some binding affinity for dopamine receptors, which necessitates comparisons between buspirone and neuroleptic agents in preclinical tests, clinical studies, and case reports. Although similarities occurred in some biochemical studies, neuroleptics, and not buspirone, caused an increase in dopamine receptors with chronic use. Neuroleptics typically produce this change after long-term use, which is thought to be a key factor leading to tardive dyskinesia. In standard animal behavior studies, buspirone's profile failed to match neuroleptic agents. Most notably, neuroleptics produce catalepsy; however, buspirone failed to induce catalepsy and instead reversed this effect. Isolated case reports have described buspirone as causing movement disorders, but these patients were previously exposed to neuroleptic agents. Furthermore, buspirone has been used successfully to treat anxiety in parkinsonism without exacerbating existing movement problems. In psychotropic drug use, careful patient monitoring, complete drug histories, and a full appreciation for a drug's pharmacology are necessary to decipher any likelihood of a drug relation with an adverse effect. PMID- 2185607 TI - Heterotopic pregnancy: a reevaluation. AB - Heterotopic pregnancies, or combined intrauterine and extrauterine pregnancies, were first reported in 1708. Traditionally, the rate of occurrence has been thought to be 1:30,000 pregnancies. It has even been said in the recent literature that an intrauterine pregnancy would rule out an ectopic pregnancy. There is good evidence that this is no longer true. The reported incidence in Western Europe and the United States is most probably 1:2600 pregnancies and much higher in certain high-risk groups. Because heterotopic pregnancy is no longer a medical curiosity, it needs to be considered in the differential diagnosis of abdominal pain in pregnancy, in the management of ectopic pregnancy, and in ovulation induction. This report presents a case encountered in a typical family practice. The literature is reviewed, and probable factors responsible for the markedly increased rate (ovulation induction and increase in ectopics in general) are addressed. PMID- 2185608 TI - Grateful Med. PMID- 2185609 TI - Esophagogastroduodenoscopy by family physicians: a national multisite study of 717 procedures. AB - This is the first multisite report of esophagogastroduodenoscopies (EGDs) performed by family physicians. The first 717 EGDs performed by family physicians from 8 separate office practices provide a practical and safe rationale for selected cognitive and psychomotor aspects of continuing medical education after residency training. Although primarily in private practice, these physicians were affiliated with 6 academic institutions. This group of family physicians received training in short courses. The average amount of hands-on training before independent EGD was 8 supervised cases. Cumulatively, these data represent 227 months (18.9 years) of office practice. All cases were collected sequentially from the beginning of each physician's experience, and 454 cases were collected prospectively. Physicians reported excellent patient tolerance. Diagnostic yields were high, and biopsies were performed where appropriate. Pathologists reviewed biopsy specimens from 213 sites. The family physician endoscopic diagnosis agreed with the tissue diagnosis in 188 cases (88 percent). Physicians believed that EGD enhanced management or changed the diagnosis in more than 89 percent of cases. One bleeding complication requiring overnight hospitalization was noted. This complication rate 0.0014 (1/717) compares favorably with published subspecialty complication rates 0.0013 (1.3/1000). These data confirm the ability of some family physicians to perform EGD and suggest that continuation is safe. Biopsy analysis indicates diagnostic accuracy is high. Further study on the cognitive aspects and the defragmentation of care is needed. PMID- 2185610 TI - Chlamydia trachomatis urethritis in university men: risk factors and rates. AB - This study reports the rates of Chlamydia trachomatis genital infection in two groups of university men. One hundred twenty-seven came to the student health center with genitourinary complaints, and 29 were identified as the sexual partners of women with chlamydia infections. Evidence of chlamydial infection was found in 29 (22.8 percent) of those presenting with complaints and in 6 (20.7 percent) who were contacts of chlamydia-infected women. Comparison of all symptomatic patients with sexually active controls without genitourinary complaints showed that the symptomatic patients had significantly more frequent exposures to different sexual partners and that they, or their partners, were more likely to have had a sexually transmitted disease. Chlamydial urethritis was significantly more frequent than "nonspecific" urethritis in symptomatic patients who claimed membership in a campus fraternity (P = 0.004). Complaints more likely to be noted with chlamydia included itching (P = 0.004), burning on urination (P = 0.0325), and purulent discharge (P = 0.036). PMID- 2185611 TI - Computerized administration of alcoholism screening tests in a primary care setting. AB - This study compared the use of computerized versus paper-and-pencil administration of three commonly employed alcohol screening tests--the Short Michigan Alcoholism Screening Test (SMAST-13), CAGE (an acronym for four questions to discern problem drinking), and a quantity-frequency scale. These instruments were administered to 280 adults receiving health care in three primary care clinics in south-central Wisconsin. One hundred forty patients were randomly assigned to complete these instruments on a Macintosh SE, and 140 were assigned to the paper-and-pencil versions. Patients were classified as alcoholic based on responses to the Diagnostic Interview Schedule and DSM-III criteria. Results indicated the sensitivity and specificity of these instruments were similar for the two methods of administration. The sensitivity of the SMAST-13 was 0.56 for computer administration and 0.58 for the pencil-and-paper form. The findings suggest that computer administration of these instruments is at least as effective as use of the standard pencil-and-paper method. The data show that computers can be used for direct entry of information by patients, avoiding separate coding of paper-and-pencil information into a computerized format for clinical systems that use system-wide computerization of medical information. PMID- 2185612 TI - [Pulmonary embolism: a diagnostic approach]. AB - The diagnosis of pulmonary embolism (PE) has always been a major challenge to hospital practice. As a consequence of the significant failure in diagnosis using clinical criteria alone, more advanced methods like lung scintigraphy and angiography--although unavailable at many clinical centres--have definitely improved the diagnosis efficiency in PE. The author briefly reviews the utility of clinical, analytical, electrocardiographic, radiologic, echocardiographic and phlebographic approaches to PE diagnosis. Emphasizing the risks of empiric anticoagulation, the necessity of precise diagnosis using lung scan and arteriography is discussed. The use of two alternative algorithmic approaches is suggested as a guide for diagnosis of PE, depending on the availability of sophisticated diagnostic methods in medical units. In a final overview, the author reviews some of the new methods used in the diagnosis of PE, already established as clinically useful or in ways of becoming so. PMID- 2185613 TI - Osteoporosis and osteopenia. PMID- 2185614 TI - Parathyroid hormone stimulates formation of inositol phosphates in a membrane preparation of canine renal cortical tubular cells. AB - Recent studies have shown that, in addition to its well-known action to stimulate adenylate cyclase activity, parathyroid hormone (PTH) may stimulate the inositol phosphate second messenger system in its target tissues, bone and kidney. We have developed a membrane preparation of canine renal cortex to test this hypothesis. We also have examined the potential role of guanine nucleotides on the formation of inositol phosphates (IPs) in this tissue. Collagenase-dispersed tubules were labeled with [3H]inositol, and membranes containing labeled phospholipase C (PLC) substrates ([3H]phosphatidyl inositol, [3H]phosphatidylinositol monophosphate, and [3H]phosphatidylinositol bisphosphate) were prepared. bPTH-(1-34) (100 nM) rapidly increased levels of all measured [3H]IPs (IP1, IP2, and IP3) 1.6-1.7-fold within the first 30 s of stimulation. The half-maximal concentration for the response to bPTH-(1-34) was approximately 8 nM. GTP gamma S (100 microM), a nonhydrolyzable analog of GTP, also increased levels of the three [3H]IPs (1.8 to 2.8-fold). The half-maximal concentration for the response to GTP gamma S was approximately 30 microM. In the presence of GTP gamma S, bPTH-(1-34) increased levels of IPs by up to 2.7 times more than GTP gamma S alone. The results indicate that bPTH-(1-34) can stimulate the formation of inositol phosphates in the kidney and suggest that PTH may activate a receptor coupled to this effect through a guanine nucleotide regulatory protein. PMID- 2185615 TI - Adolescent separation-individuation and family transitions. AB - This paper discusses the relationship between family structure and the achievement of the adolescent developmental task of separation-individuation. Adolescent separation-individuation is viewed as a continuum. At the right end of the continuum, adolescents reach successful therapeutic separation-individuation- a sense of self--while remaining connected to the family as a functional member. At the other end of the continuum is nontherapeutic dysfunctional separation individuation. These adolescents are characterized by disruptive behaviors, rejection of societal and family norms, and potential suicide. Successful accomplishment of separation-individuation appears to be affected by a number of factors (e.g., conflict, parental relationship, accomplishment of previous developmental tasks). Adolescents from nontraditional families may have more barriers to overcome in order to therapeutically complete this task. Interventions to promote therapeutic separation-individuation need to incorporate all members of the family and support from the community. Through anticipatory guidance, dissemination of information, affiliating behaviors, and support groups, practitioners can help equip families with the skills needed for successful accomplishment of this task. PMID- 2185616 TI - Notes on the history of adolescent inpatient and residential treatment. AB - This study surveys some of the major theoretical contributions to the evolvement of concepts about adolescence. Historical perspectives regarding the development of inpatient and residential institutions are outlined, followed by brief discussions of follow-up studies evaluating both forms of treatment. Finally, a general overview of outcome research is provided, focusing on the underlying, changing attitudes toward the adolescent phase of development. PMID- 2185617 TI - Breast reduction and mastopexy, an old love story: B technique update. AB - In summary, the recent findings of my personal experience with the B technique have been quite helpful and rewarding. I found that drawing a lateral angle when planning the procedure obtains a more circular areola contour and avoids last moment modifications. Also, upper pole undermining allows for an upper pole horizontal plication in the cases of a simple mastopexy. Figures 4 and 5 show results of the B technique. These modifications have been used over the last four years with no special complications and very satisfactory results. PMID- 2185618 TI - Early history of lipoplasty in the United States. PMID- 2185619 TI - A new periareolar mammaplasty: the "round block" technique. AB - The "round block" acts as a keystone supporting the mammary cone. The keystone lies in the dermodermic, glandulo-glandular, and glandulo-musculoperiosteal unions fixed definitively with nonresorbable suture, by a crisscross mastopexy, and by a circular nonresorbable suture of woven nylon included in the periareolar circular dermo-dermic scar block. This technique can be used in numerous types of breast surgery: In cases of ptosis or hypertrophy, it allows the scar to go up to the periareolar circle which is in itself generally inconspicuous. In cases of hypotrophy, the use of the round block technique permits easy access for insertion of the prosthesis as it simultaneously corrects ptosis. In cases of tumoral excision, the round block produces a discreet scar and a more regular breast contour. In all types of mammoplasty, the main goal is to limit the scar. The scar in the submammary fold is visible, particularly when one is lying down. The ideal result is confining the scar to the periarolar area. PMID- 2185620 TI - Food energy requirements in humans. AB - The general principles behind the estimation of energy requirements in humans are discussed and a framework is proposed for estimation of energy allowances appropriate to the population of the United States. Although median weights are used for those less than 18 y, lowest mortality values, which approximate the 25th percentile weights for height in the US population, are used as the desirable weights for adults in assessing daily energy needs. For adults the procedure for estimating daily energy allowances involves calculation of resting energy expenditure by use of the Harris-Benedict equation, which is then multiplied by appropriate factors for activity. A factorial approach is followed for the additional needs of pregnancy and lactation. For young children allowances are based on intake data. Tabular data are presented for energy allowances at all ages together with worked examples for a more individualized approach when body size and activity patterns differ significantly from the mean. PMID- 2185621 TI - Protein requirements in humans. AB - The general principles underlying protein requirements are outlined and daily allowances for protein are derived appropriate to the various age and sex population subgroups of the United States. Median body weights are however used for all age groups of the population rather than the desirable body weights used previously for adults. Following the recommendations of the FAO/WHO/UNU international working group, the protein requirement for male and female adults was taken as 0.6 g.kg-1.d-1 of high-quality highly digestible protein. By use of an age-specific scoring system and the mean amino acid composition and digestibility of the US diet, this allowance became 0.83 g.kg-1.d-1 of mixed US dietary protein--a value similar to the previous RDA but derived in a different manner. Tabulated daily protein allowance data are presented for reference age and sex groups for the US population (child-adult) together with the additional needs of pregnancy and lactation. PMID- 2185622 TI - Trend changes in use and current intakes of tropical oils in the United States. AB - To evaluate the need for and potential public health impact of selective labeling of foods containing tropical oils (TOs), we examined trend changes in use of TOs in the United States from 1963 to 1985 and estimated current intakes of total fat (FI) and saturated fatty acids (SFAI) attributable to TOs. Although world production of TO has increased rapidly since 1970, use in the United States has not followed the world trend. A large portion of TOs in the United States was used in nonfood products. Estimates of current intake of TOs by selected US population groups revealed only minor contribution of TOs to the daily FI and SFAI in the United States. In 1985 the most reasonable estimate of the average FI from all three TOs represented less than 4% of total daily FI or less than 2% of daily energy intake. Three TOs combined contributed less than or equal to 8% to the daily SFAI of the three sex and/or age groups examined. PMID- 2185623 TI - Acute ingestion of glucose decreases plasma pyridoxal 5'-phosphate and total vitamin B-6 concentration. AB - The effect of the acute ingestion of glucose on the concentration of pyridoxal 5' phosphate (PLP) and total vitamin B-6 (TB6) in plasma was studied. Five males and four females were given 1 g D-glucose/kg body wt. A blood sample was collected at 0-10 min and 0, 0.5, 1, 2, 3, 4, and 5 h and the plasma was analyzed for PLP and TB6. There was a significant decrease in both plasma PLP and TB6 (p less than 0.05) at 2 h. All nine subjects exhibited a decrease, and by 5 h the mean change from fasting was 8-10 nmol/L for PLP and 8-12 nmol/L for TB6 (an 18-21% decrease from that when fasting). Ingestion of 300 mL water in four subjects resulted in a mean decrease of 3.4 nmol PLP/L plasma and indicated that some but not all of the decrease may have been due to fluid ingestion per se. Ingestion of glucose is associated with a decrease in both circulating plasma PLP and TB6; therefore, carbohydrate ingestion should be considered when plasma PLP and TB6 concentrations are used to evaluate vitamin B-6 status. In addition, fasting blood samples should be used when evaluating vitamin B-6 status. PMID- 2185624 TI - Increased plasma lipid peroxidation in riboflavin-deficient, malaria-infected children. AB - Plasma lipid peroxides were measured as malonyldialdehyde (MDA) by the thiobarbituric acid (TBA) method in 75 children suffering from Plasmodium falciparum malaria. Their riboflavin status was assessed by measuring erythrocyte glutathione reductase activation coefficients (EGRACs), and values greater than 1.40 were regarded as indicating biochemical deficiency. Plasma MDA was higher (p less than 0.001) in patients than in control subjects; the concentrations were 3.65 +/- 0.70 and 1.77 +/- 0.45 mumol/L (means +/- SD), respectively. The riboflavin-deficient group had higher plasma MDA values (3.98 +/- 0.70 mumol/L) than did the nondeficient group (3.30 +/- 0.68 mumol/L, p less than 0.001). Plasma MDA concentrations correlated with EGRACs (r = 0.46, p less than 0.01) in the patients. It is proposed that riboflavin deficiency restricts regeneration of reduced glutathione making the parasitized erythrocytes more vulnerable to destructive lipid peroxidation and increasing plasma lipid hydroperoxides. PMID- 2185625 TI - Urinary chromium excretion and insulinogenic properties of carbohydrates. AB - Eleven male and nine female adult subjects were given one of the following five carbohydrate-drink combinations (per kg body wt) on five mornings separated by greater than or equal to 2 wk: 1) 1.0 g glucose, 2) 0.9 g uncooked cornstarch, 3) 1.0 g glucose followed 20 min later by 1.75 g fructose, 4) 0.9 g uncooked cornstarch followed 20 min later by 1.75 g fructose, and 5) water followed 20 min later by 1.75 g fructose. Glucose plus fructose was the most insulinogenic followed by glucose alone, starch plus fructose, starch alone, and water plus fructose. The urinary losses of chromium followed a similar pattern. Subjects with the highest concentrations of circulating insulin displayed decreased ability to mobilize chromium on the basis of urinary chromium excretion. Therefore, urinary chromium losses are related to the insulinogenic properties of carbohydrates. PMID- 2185626 TI - Experimental sodium depletion and salt taste in normal human volunteers. AB - To examine the sensory effects of extreme sodium depletion in humans, 10 normal volunteers were fed a very-low-sodium diet and were treated with diuretics for 10 d. Urine samples were collected and blood was drawn for hormone analyses. Taste tests included threshold and intensity judgments of salt (NaCl) and sucrose and preferences for salt and sucrose in foods. Subjects also rated the pleasantness of 29 foods listed on a questionnaire. Substantial sodium depletion was induced in all subjects. Salt thresholds decreased in a majority of the subjects whereas preference judgments for salt in foods tended to be greater during the depletion period. The changes in pleasantness of the 29 foods revealed that saltier foods were substantially more attractive during the depletion period than during the pre- and postdepletion periods. These data indicate that experimental sodium depletion in humans is followed by moderate sensory changes and an increased preference for salty foods. PMID- 2185627 TI - Mortality rates among dialysis patients in Medicare's End-Stage Renal Disease Program. AB - Medicare's End-Stage Renal Disease (ESRD) Program provides funding for life saving renal replacement therapy for patients with irreversible chronic renal failure. Although more than 100,000 patients are currently alive due to dialysis and transplantation, mortality among ESRD patients is still much higher than in the general population. Gross mortality, calculated from aggregate statistics such as those available from the annual ESRD facility survey, is an extremely imprecise measure of mortality and can lead to misleading conclusions. Standard methods of survival calculation such as actuarial life-table analyses provide more accurate descriptions of variations and trends in mortality. The most important characteristic influencing mortality among ESRD patients on dialysis is the changing age and diagnostic distribution. The average age of dialysis patients has increased by over 5 years during the past decade. Patients whose renal failure is attributed to diabetic nephropathy currently account for 30% of all patients initiating renal replacement therapy each year and constitute the fastest growing group of ESRD patients. From 1982 to 1987, 1-year survival on dialysis was 72.7% for patients whose renal failure was attributed to diabetic nephropathy and 79.8% for all other patients. Survival decreases rapidly with advancing age at time of renal failure, from 95.1% among patients 15 to 24 years to 52.5% for patients over the age of 85 (for non-diabetics). Survival rates for whites are 5% to 6% lower than for other racial categories. There are no obvious trends in mortality among dialysis patients over the past decade. For patients whose renal failure is attributed to diabetic nephropathy, survival rates have remained constant despite overall aging in this group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185628 TI - Study of the Medicare End-Stage Renal Disease program. PMID- 2185629 TI - Hereditary cranium bifidum and symmetric parietal foramina are the same entity. AB - Cranium bifidum is literally "cleft skull." Numerous reports describe the anatomy of this defect, and crude estimates of the population prevalence suggest it is a relatively infrequent occurrence. McKusick's catalog contains only one family with cranium bifidum but several familial reports of symmetrical parietal foramina. Available information indicates that cranium bifidum and symmetrical parietal foramina are inherited in an autosomal dominant fashion and occur in orientals, blacks, whites, and native Americans. Here we report on a family with serial radiographs that document ontogenic development of parietal foramina in late childhood and adulthood from apparent cranium bifidum and parietal foramina during infancy and early childhood. We conclude that these are the same entity, differentiated only by the time during life in which the defect is demonstrated. PMID- 2185630 TI - Arthur Robinson--an appreciation. PMID- 2185631 TI - Living history: an autobiography of Arthur Robinson. PMID- 2185632 TI - Johanson-Blizzard syndrome: clinical spectrum and further delineation of the syndrome. AB - We report on 2 patients with Johanson Blizzard syndrome and review the literature, in an attempt to further characterize the clinical spectrum of this disorder. PMID- 2185633 TI - Dubowitz syndrome: possible evidence for a clinical subtype. AB - Clinico-genetic analysis of 21 personal observations and review of the literature confirmed the existence of a wide phenotypic spectrum of Dubowitz syndrome. It is shown that in spite of marked microcephaly, severe mental deficiency is rare in Dubowitz syndrome and about half of the patients are mentally normal. A "new" clinical subtype is defined, which also includes anorectal anomalies and premature craniosynostosis. All three families with this form are natives of a small area of Byelorussia, suggesting an autosomal or X-linked recessive mode of inheritance of this subtype. The data obtained confirm autosomal recessive inheritance of Dubowitz syndrome. PMID- 2185634 TI - Double chromosome anomaly: interstitial deletion 5q and reciprocal translocation (1;11)(p22;q21). AB - We describe a girl with multiple congenital abnormalities and developmental delay; her karyotype showed an apparently balanced translocation between the short arm of chromosome 1 and the long arm of chromosome 11, and an interstitial deletion of the long arm of chromosome 5 (q15q31). The clinical findings are compared with those described in other cases of 5q deletion, and the origin of the chromosome rearrangements is briefly discussed. PMID- 2185635 TI - Detection of heterozygotes for recessive alleles. Homocyst(e)inemia: paradigm of pitfalls in phenotypes. AB - Excess homocysteine in body fluids has been implicated as a factor in the pathogenesis of occlusive vascular disease (peripheral and cerebrovascular arterial disease, and perhaps coronary artery disease). Heterozygotes for inborn errors of homocysteine metabolism (transsulfuration or remethylation pathways) are much more frequent than are homozygotes/compounds. If heterozygotes are at increased risk (a question not addressed here), it is of interest to know whether they can be identified consistently by a "screening" measurement of blood homocyst(e)ine. We used hyperhomocyst(e)inemia (cystathioninemia beta-synthase deficiency) as a test case. From reviews of metabolite values in blood samples either fasting (11 articles) or after a methionine load (8 articles), and of measures of enzyme activity (12 articles), it is apparent that (1) The heterozygous phenotype cannot be identified consistently by any single measure (there is overlap with normal values); and (2) the exaggerated gene dosage effect (negative allelic complementation) present in most heterozygotes does not assist their classification. The failure of enzyme assay to distinguish heterozygotes consistently (relative to normal values) may reflect allelic heterogeneity. The failure of metabolic values to identify heterozygotes consistently reflects the local and global properties of the homeostatic system controlling the homocysteine pool size. The problem described here is a particular example of a general one in physiological and medical genetics, namely detection of heterozygotes for recessive alleles, affecting metabolic homeostasis, for purposes of medical intervention and for genetic counselling. PMID- 2185636 TI - Apparently nonmosaic trisomy 22: clinical report and review. AB - We report on apparently nonmosaic trisomy 22 in a liveborn girl with multiple congenital anomalies. The abnormalities were growth retardation; microcephaly; hypertelorism; epicanthic folds; anti-mongoloid slant; apparently low-set, malformed ears; highly arched, cleft palate; short webbed neck; and hypoplastic nails. The extra 22 was found to be of maternal origin by chromosome polymorphism. PMID- 2185637 TI - Persistent hyperplastic primary vitreous associated with protein C deficiency. PMID- 2185638 TI - Acute infantile leukocoria. PMID- 2185639 TI - Effects of elevated temperature on protein breakdown in muscles from septic rats. AB - Elevated temperature has been proposed to contribute to accelerated muscle protein degradation during fever and sepsis. The present study examined the effect of increased temperature in vitro on protein turnover in skeletal muscles from septic and control rats. Sepsis was induced by cecal ligation and puncture (CLP); control rats were sham operated. After 16 h, the extensor digitorum longus (EDL) and soleus (SOL) muscles were incubated at 37 or 40 degrees C. Protein synthesis was determined by measuring incorporation of [14C]phenylalanine into protein. Total and myofibrillar protein breakdown was assessed from release of tyrosine and 3-methylhistidine (3-MH), respectively. Total protein breakdown was increased at 40 degrees C by 15% in EDL and by 29% in SOL from control rats, whereas 3-MH release was not affected. In muscles from septic rats, total and myofibrillar protein breakdown was increased by 22 and 30%, respectively, at 40 degrees C in EDL but was not altered in SOL. Protein synthesis was unaffected by high temperature both in septic and nonseptic muscles. The present results suggest that high temperature is not the primary mechanism of increased muscle protein breakdown in sepsis because the typical response to sepsis, i.e., a predominant increase in myofibrillar protein breakdown, was not induced by elevated temperature in normal muscle. It is possible, however, that increased temperature may potentiate protein breakdown that is already stimulated by sepsis because elevated temperature increased both total and myofibrillar protein breakdown in EDL from septic rats. PMID- 2185640 TI - Effects of phenylarsine oxide on stimulation of glucose transport in rat skeletal muscle. AB - The trivalent arsenical phenylarsine oxide (PAO) inhibits insulin-stimulated glucose transport in adipocytes and skeletal muscle through direct interactions with vicinal sulfhydryls. In muscle, glucose transport is also activated by contractile activity and hypoxia. It was therefore the purpose of the present study to investigate whether vicinal sulfhydryls are involved in the stimulation of glucose transport activity in the isolated rat epitrochlearis muscle by hypoxia or contractions. PAO (greater than 5 microM) caused a twofold increase in rate of transport of the nonmetabolizable glucose analogue 3-O-methylglucose (3 MG) that was completely prevented by cytochalasin B, the vicinal dithiol dimercaptopropanol, dantrolene, or 9-aminoacridine, both inhibitors of sarcoplasmic reticulum Ca2+ release, or omission of extracellular Ca2+. Although PAO treatment (greater than or equal to 20 microM) prevented approximately 80% of the increase in 3-MG transport caused by insulin, it resulted in only a approximately 50% inhibition of the stimulation of 3-MG transport by either hypoxia or contractile activity. PAO treatment (40 microM) of muscles already maximally stimulated by insulin, contractile activity, or hypoxia did not reverse the enhanced rate of 3-MG transport. These data suggest that vicinal sulfhydryls play a greater role in the activation of glucose transport by insulin than by muscle contractions or hypoxia. The finding that PAO inhibits the stimulation of glucose transport, but does not affect glucose transport after it has been stimulated, provides evidence that vicinal sulfhydryls are involved in the pathways for glucose transport activation in muscle, but not in the glucose transport mechanism itself. PMID- 2185641 TI - Lipoprotein lipase: cellular origin and functional distribution. AB - Lipoprotein lipase (LPL, E.C. 3.3.1.34) is the enzyme responsible for hydrolysis of triacylglycerols in plasma lipoproteins, making the fatty acids available for use by subjacent tissues. LPL is functional at the surface of endothelial cells, but it is not clear which cells synthesize the enzyme and what its distribution is within tissues and vessels. We have searched for specific cell expression of the LPL gene by in situ hybridization using a RNA probe and for the corresponding protein distribution by immunocytochemistry on cryosections of some LPL-producing tissues of guinea pigs. In white and brown adipose tissues, heart and skeletal muscle, and lactating mammary gland, there was positive hybridization for LPL mRNA over all members of the major cell types, indicating that mature and immature adipocytes, muscle cells, and mammary epithelial cells are main sources of LPL. In large vessels, LPL expression was detected in some smooth muscle cells in the media layer. There was no positive hybridization for LPL mRNA over endothelial cells in any of the tissues studied, but there was immunoreaction for LPL protein at endothelial surfaces of all blood vessels. In the kidney, there was strong immunofluorescence at the vascular endothelium, particularly in the glomeruli, but little or no LPL mRNA was detected in the surrounding cells. These observations suggest that in some tissues LPL is synthesized by parenchymal cells and spreads along the vascular mesh. Transfer to the vascular endothelium is, however, not the only route taken by LPL. In the mammary gland most of the enzyme protein appeared to be secreted, partly in association with milk fat droplets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185642 TI - Exercising mammals synthesize stress proteins. AB - Spleen cells, peripheral lymphocytes, and soleus muscles were removed from male Sprague-Dawley rats that had been run on a treadmill (24 m/min) for either 20, 40, or 60 min or to exhaustion (86 +/- 41 min) and were labeled in vitro with [35S]methionine at 37 degrees C. Similar tissues from nonrunning control rats were labeled in vitro at either 37 or 43 degrees C (heat shock). Fluorographic analyses of one- and two-dimensional polyacrylamide gel electrophoretic separations of the proteins from cells and tissues of exercised rats demonstrate the new or enhanced synthesis of proteins of approximately 65, 72, 90, and 100 kDa. Although synthesis of these proteins is low or not detectable in tissues from control rats labeled at 37 degrees C, they are prominent products of similar tissues labeled under heat-shock conditions (43 degrees C) and, in fact, correspond in Mr and pI with the so-called heat-shock proteins. These results suggest that exercise is a sufficient stimulus to induce or enhance the synthesis of heat shock and/or stress proteins in mammalian cells and tissues. PMID- 2185643 TI - Glucagon-cortisol interactions on glucose turnover and lactate gluconeogenesis in normal humans. AB - To determine the mechanism for cortisol enhancement of glucagon-stimulated overall hepatic glucose output (OHGO), we employed the glucose-insulin clamp technique with infusions of [6-3H]glucose and [U-14C]lactate and measured OHGO, glucose utilization, and the turnover and incorporation of lactate in plasma glucose in normal volunteers under four experimental conditions: 1) normoglucagonemia (approximately 150 pg/ml)- normocortisolemia (approximately 14 micrograms/dl); 2) isolated hyperglucagonemia (approximately 550 pg/ml); 3) isolated hypercortisolemia (approximately 32 micrograms/dl); and 4) combined hyperglucagonemia-hypercortisolemia. Isolated hyperglucagonemia caused initial increases in OHGO and lactate gluconeogenesis, which were maximal at 1 h (23.9 +/ 1 and 2.7 +/- 0.4 mumol.kg-1.min-1, respectively) but remained significantly above values in control experiments through 5 h (10.3 +/- 0.7 vs. 8.2 +/- 1.1, P less than 0.03; 2.2 +/- 0.4 vs. 1.2 +/- 0.3, mumol.kg-1.min-1, P less than 0.04, respectively). Hypercortisolemia has no effect on OHGO but increased lactate gluconeogenesis after 3 h. Superimposition of hypercortisolemia on hyperglucagonemia did not further increase OHGO (11.1 +/- 0.7 vs. 10.3 +/- 0.7 mumol.kg-1.min-1, P = NS) but augmented lactate gluconeogenesis additively (isolated hyperglucagonemia = 0.96, isolated hypercortisolemia = 0.98; combined = 2.02 mumol.kg-1.min-1). Neither glucagon nor cortisol affected lactate turnover or glucose utilization. We conclude that glucagon has a persistent effect on OHGO largely accounted for by increased gluconeogenesis. Cortisol augments glucagon stimulated gluconeogenesis in an additive manner best explained by changes in gluconeogenic enzymes rather than in substrate availability. Finally, the fact that cortisol increased gluconeogenesis without affecting glucose utilization suggests that the liver is more sensitive to the diabetogenic effects of cortisol than are peripheral tissues. PMID- 2185644 TI - Somatotropin in lactating cows: effect on response to epinephrine and insulin. AB - The dose dependence of plasma nonesterified fatty acids (NEFA) and glycerol responses to epinephrine was determined in lactating cows treated with bovine somatotropin (bST). Also, the effects of insulin on lipolysis and glucose clearance were examined. Lactating cows (190 +/- 24 days postpartum) received daily subcutaneous injections of methionyl bST (40 mg) or excipient during two 12 day treatment periods. Epinephrine challenges (0.1, 0.2, 0.4, 0.8, 1.2, and 1.6 micrograms/kg body wt) were administered intravenously on days 6-11 and an insulin challenge (1 microgram/kg) on day 12. Milk energy secretion increased 55% without any change in voluntary feed intake during bST treatment. Circulating concentrations of NEFA were chronically elevated and reciprocally paralleled changes in net energy balance. Maximal response of plasma NEFA and glycerol to epinephrine was markedly increased during bST treatment, whereas the dose of signal-producing half-maximal response (ED50) was unchanged. Antilipolytic effects of insulin were also enhanced, whereas the effect of insulin on the fractional rate of glucose change was reduced. Thus bST alters tissue response to homeostatic signals to allow more nutrients to be partitioned for milk synthesis. Furthermore, the alterations in response to epinephrine and insulin appear to predominantly occur at a postreceptor level. PMID- 2185645 TI - In vivo studies on paracrine actions of pituitary angiotensin II in stimulating prolactin release in rats. AB - The present experiments were performed to test the hypothesis that, in vivo, intrapituitary angiotensin II (ANG II) mediates the effect of luteinizing hormone releasing hormone (LHRH) on prolactin release. After intravenous administration of LHRH (100 ng/100 microliters saline), plasma levels of both luteinizing hormone (LH) and prolactin were increased in ovariectomized rats pretreated with estradiol and progesterone. Intravenous administration of saralasin or sarthran (ANG II receptor blockers) reduced or abolished, respectively, the LHRH-induced increase in prolactin without affecting the rise in LH. In other ovariectomized steroid-treated rats, saralasin did not affect the increase in LH or prolactin induced by 10 min of restraint stress. Finally, in intact female rats on the day of proestrus, neither saralasin nor sarthran affected the mid-cycle prolactin surge. Taken together, these results show that in vivo exogenous LHRH stimulates prolactin release via a paracrine action of pituitary ANG II. However, under other conditions in which both LH and prolactin (and presumably endogenous LHRH) are elevated, pituitary ANG II does not appear to be involved in the prolactin rise. PMID- 2185646 TI - Influence of cell heterogeneity on skeletal muscle lactate kinetics. AB - Lactate and [14C]lactate kinetics were studied in three rabbit skeletal muscle preparations with distinct fiber type profiles, glycolytic (99.1 +/- 0.2% type IIb fibers), oxidative (97.5 +/- 0.6% type I fibers), and mixed (type I, IIa, and IIb fibers). Single-pass perfusions were carried out for 2 h in the presence of lactate (1 mM), glucose (5 mM), [6-3H]glucose, and [U-14C]lactate. All preparations displayed net lactate release, [14C]lactate removal, and 14CO2 release. Net lactate release was greatest in the glycolytic preparation, 9.7 +/- 0.5 mumol.100 g-1.min-1, and least in the oxidative preparation, 3.7 +/- 0.2 mumol.100 g-1.min-1. [14C]lactate arteriovenous difference was greatest in the mixed preparation, 1,688 +/- 58 (disintegrations/min)/ml (dpm/ml), and least in the glycolytic preparation, 505 +/- 10.3 dpm/ml. Steady-state incorporation of [14C]lactate was observed in CO2, amino acids, and pyruvate. Tissue lactate specific activity (LSA) in all preparations was significantly lower than arterial LSA, but not significantly different from venous LSA. Estimates of lactate removal based on venous LSA were not significantly different from net glycolytic flux. In conclusion, 1) under basal, resting conditions net lactate release and [14C]lactate removal are properties of all fiber types, and 2) tracer estimates of lactate turnover in skeletal muscle reflect net glycolytic flux through pyruvate. PMID- 2185647 TI - Effect of 1,25 dihydroxyvitamin D3 on isolated islets from vitamin D3-deprived rats. AB - Insulin release is impaired by vitamin D3 deficiency but can be restored by in vivo administration of 1,25 dihydroxyvitamin D3 [1,25(OH)2D3]. A direct influence of 1,25(OH)2D3 on the B-cell was studied in vitro with islets from 5-wk vitamin D3-deprived rats. This hormone (10(-12) to 10(-6) mol/l) added to the incubation medium had a stimulatory dose-dependent effect on insulin response to 8.3 mmol/l glucose 6 h later. Moreover, perifusion experiments performed after different times of incubation demonstrated that after 6 h 1,25(OH)2D3 increased in particular the first phase of insulin response to 16.7 mmol/l glucose. The 45Ca fluxes, followed in parallel, were never modified by 1,25(OH)2D3 in the absence of glucose but were enhanced during the glucose stimulus, whereas 86Rb fluxes were never affected by 1,25(OH)2D3. These results demonstrated that 1,25(OH)2D3 acts in vitro on B-cells, but with a 6-h delay to potentiate the glucose-induced insulin release, concomitant with intracellular calcium redistribution. PMID- 2185648 TI - Protein and leucine metabolism in maple syrup urine disease. AB - Constant infusions of [13C]leucine and [2H5]phenylalanine were used to trace leucine and protein kinetics, respectively, in seven children with maple syrup urine disease (MSUD) and eleven controls matched for age and dietary protein intake. Despite significant elevations of plasma leucine (mean 351 mumol/l, range 224-477) in MSUD subjects, mean whole body protein synthesis [3.78 +/- 0.42 (SD) g.kg-1. 24 h-1] and catabolism (4.07 +/- 0.46) were similar to control values (3.69 +/- 0.50 and 4.09 +/- 0.50, respectively). The relationship between phenylalanine and leucine fluxes was also similar in MSUD subjects (mean phenylalanine-leucine flux ratio 0.35 +/- 0.07) and previously reported adult controls (0.33 +/- 0.02). Leucine oxidation was undetectable in four of the MSUD subjects and very low in the other three (less than 4 mumol.kg-1.h-1; controls 13 20). These results show that persistent elevation in leucine concentration has no effect on protein synthesis. The marked disturbance in leucine metabolism in MSUD did not alter the relationship between rates of catabolism of protein to phenylalanine and leucine, which provides further support for the validity of the use of a single amino acid to trace whole body protein metabolism. The minimal leucine oxidation in MSUD differs from findings in other inborn metabolic errors and indicates that in patients with classical MSUD there is no significant route of leucine disposal other than through protein synthesis. PMID- 2185649 TI - Triglyceride kinetics, tissue lipoprotein lipase, and liver lipogenesis in septic rats. AB - The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studied by examining liver production and clearance of very-low density lipoprotein (VLDL) triglyceride (TG). To assess liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant iv infusion of [2-3H]glycerol-labeled VLDL. Clearance of VLDL-TG was also evaluated by measuring activities of lipoprotein lipase (LPL) in heart, soleus muscle, and adipose tissue from fasted control, fasted E. coli-treated, fed control, and fed E. coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 x 10(7) live E. coli colonies per 100 g body wt. Twenty-four hours after E. coli injection, serum TG, free fatty acids (FFA), and cholesterol of fasted E. coli treated rats were elevated by 170, 76, and 16%, respectively. The elevation of serum TG may be attributed to the 67% decrease in clearance rate of VLDL-TG in fasted E. coli-treated rats compared with their fasted controls. The suppressed activities of LPL in adipose tissue, skeletal muscle, and heart were consistent with reduced clearance of TG. Secretion of VLDL-TG declined by 31% in livers of fasted E. coli-treated rats, which was accompanied by a twofold increase in the composition of liver TG. Rates of in vivo TG synthesis in livers of the fasted E. coli-treated rats were twofold higher than in those of fasted control rats. Decreased rate of TG appearance along with the increase in liver synthesis of TG contributed to the elevation of liver lipids in the fasted E. coli-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185650 TI - Glycogenesis and glyconeogenesis in skeletal muscle: effects of pH and hormones. AB - We examined the effects of selected hormones and pH on the rates of glyconeogenesis (L-[U-14C]-lactate----glycogen) and glycogenesis (D-[U 14C]glucose----glycogen) in mouse fast-twitch (FT) and slow-twitch muscles incubated in vitro (37 degrees C). Glyconeogenesis and glycogenesis increased linearly with increasing concentrations of lactate (5-20 mM) and glucose (2.5-10 mM), respectively, in both muscles. Glyconeogenesis was approximately three- to fourfold greater in the extensor digitorum longus (EDL) than in the soleus, whereas basal glycogenesis was twofold greater in the soleus muscle than in the EDL. Lactate accounted for up to 5% of the glycogen formed in the soleus and up to 32% in the EDL relative to the rates of glycogenesis (i.e., 5 mM glucose + 10 nM insulin) in each muscle. Corticosterone (10(-12)-10(-6) M) failed to alter glyconeogenesis, whereas this hormone reduced glycogenesis. Insulin (10 nM) markedly stimulated glycogenesis but failed to stimulate glyconeogenesis. The rates of both glycogenesis and glyconeogenesis were pH sensitive, with optimal rates at pH 6.5-7.0 in both muscles. Glyconeogenesis increased by 49% in the soleus and by 39% EDL at pH 6.5 compared with pH 7.4. Glycogenesis increased in the soleus (SOL) and EDL in the absence (SOL: +22%; EDL: +52%) and presence of insulin (SOL: +22%; EDL: +51%) at pH 6.5 when compared with pH 7.4. In additional experiments with the perfused rat hindquarter, rates of glyconeogenesis were shown to be highly correlated with proportion of FT muscle fibers in a muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185651 TI - Pentobarbital reduces basal liver glucose output and its insulin suppression in rats. AB - Recent reports conflict on the effect that pentobarbital anesthesia has on basal glucose turnover in the rat. It is also unclear whether pentobarbital alters insulin suppressibility of hepatic glucose production (Ra). We examined these issues by performing basal and hyperinsulinemic euglycemic clamp studies in anesthetized and conscious animals. Ra and glucose utilization (Rd) were estimated using a steady-state infusion of 3-[3H]glucose. Pentobarbital anesthesia in normothermic rats transiently elevated plasma glucose but resulted in a sustained suppression of basal Ra (10.4 +/- 0.3 vs. conscious 13.2 +/- 0.9 mg.kg-1.min-1, P less than 0.05). In the insulin-stimulated state (110 mU/l), despite similar plasma glucose and insulin levels, clamp glucose infusion rate was significantly reduced in anesthetized animals (11.1 +/- 0.9 vs. conscious 23.6 +/- 1.3 mg.kg-1.min-1, P less than 0.001). This can be attributed to both a significantly lower insulin-stimulated Rd (15.4 +/- 1.3 vs. conscious 22.8 +/- 1.4 mg.kg-1.min-1, P less than 0.005) and reduced insulin suppression of Ra (4.3 +/- 0.8 vs. conscious -0.8 +/- 0.5 mg.kg-1.min-1, P less than 0.001; i.e., anesthetized 59% vs. conscious 100% reduction of basal Ra). Thus pentobarbital anesthesia significantly reduces basal Ra and induces hepatic insulin resistance (reduces Ra suppressibility). Pentobarbital effects are not dependent on induced hypothermia, but this exacerbates the metabolic perturbation. Caution should be used in extrapolating from the anesthetized to the conscious state. PMID- 2185652 TI - Isolation and culture of alveolar type II cells. AB - The alveolar type II cell performs many important functions within the lung, including regulation of surfactant metabolism, ion transport, and alveolar repair. Because type II cells comprise only 15% of all lung cells, it is difficult to attribute specific functions to type II cells from studies of whole lungs or mixed cell cultures. At the present time, there is no passaged line that exhibits the full range of known type II cell functions. For these reasons, investigators have used isolated type II cells to study alveolar cell biology, biochemistry, and molecular biology. This review addresses many of the issues involved in isolating and culturing type II cells, including the choice of a method of isolating cells, the importance of using specific markers of the differentiated type II cell phenotype, and the problems of maintaining these differentiated phenotypic characteristics in tissue culture. PMID- 2185653 TI - Recent stereological methods for cell biology: a brief survey. AB - With the advent of many new tools over the last five years, stereology has become simpler, assumption-free, and more efficient but, at the same time, new terms and concepts have proliferated, which risk overwhelming potential users. The present review is intended to meet the urgent need for a structured classification and evaluation of the newest stereological methods. Being fairly comprehensive, the exposition is necessarily succinct: the reader is referred to selected references for the necessary details and examples. PMID- 2185654 TI - A genetic approach to the study of lung physiology: understanding biological variability in airway responsiveness. AB - Genetic techniques are generally applicable to almost any trait or physiological process for which biological variability can be demonstrated. These methods have not commonly been applied to studies on lung pathophysiology, however. The aim of this commentary will be to introduce and discuss the potential application of genetic methods to research on the pathophysiology of asthma. Recent efforts to identify genes that determine airway hyperresponsiveness in the genetically standardized inbred laboratory mouse will be reviewed. These experiments demonstrate how genetic background influences the expression of airway responsiveness to certain environmental stimuli and illustrate the application of selected genetic resources. A discussion follows on how these genetic models may potentially provide insight into asthma and our understanding of the molecular physiology and genetic regulation of airway hyperreactivity to various stimuli. PMID- 2185655 TI - Lung epinephrine synthesis. AB - We studied in vitro and in vivo epinephrine (E) synthesis by rat lung. Nine days after removal of the adrenal medullas, circulating E was reduced to 7% of levels found in sham-operated rats but 30% of lung E remained. Treatment of demedullated rats with 6 hydroxydopamine plus reserpine did not further reduce lung E. In the presence of S-[3H]adenosylmethionine lung homogenates readily N-methylated norepinephrine (NE) to form [3H]E. The rate of E synthesis by lung homogenates was progressively more rapid with increasing NE up to a concentration of 3 mM, above which it declined. The rate of E formation was optimal at an incubation pH of 8 and at temperatures of approximately 55 degrees C. We compared the E-forming enzyme(s) of lung homogenates with those of adrenal and cardiac ventricle. The adrenal contains mainly phenylethanolamine N-methyltransferase (PNMT), which is readily inhibited by SKF 29661 and methylates dopamine (DA) very poorly. Cardiac ventricles contain mainly nonspecific N-methyltransferase (NMT), which is poorly inhibited by SKF 29661 and readily methylates both DA and NE. Lung homogenates were inhibited by SKF 29661 about half as well as adrenal but more than ventricle. We used the rate of E formation from NE as an index of PNMT-like activity and deoxyepinephrine synthesis from DA as an index of NMT-like activity. PNMT and NMT activity in rat lung homogenates were not correlated with each other, displayed different responses to change in temperature, and were affected differently by glucocorticoids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185656 TI - Sixty years of surfactant research. PMID- 2185657 TI - Mechanisms by which mitochondria transport calcium. AB - It has been firmly established that the rapid uptake of Ca2+ by mitochondria from a wide range of sources is mediated by a uniporter which permits transport of the ion down its electrochemical gradient. Several mechanisms of Ca2+ efflux from mitochondria have also been extensively discussed in the literature. Energized mitochondria must expend a significant amount of energy to transport Ca2+ against its electrochemical gradient from the matrix space to the external space. Two separate mechanisms have been found to mediate this outward transport: a Ca2+/nNa+ exchanger and a Na(+)-independent efflux mechanism. These efflux mechanisms are considered from the perspective of available energy. In addition, a reversible Ca2(+)-induced increase in inner membrane permeability can also occur. The induction of this permeability transition is characterized by swelling of the mitochondria, leakiness to small ions such as K+, Mg2+, and Ca2+, and loss of the mitochondrial membrane potential. It has been suggested that the permeability transition and its reversal may also function as a mitochondrial Ca2+ efflux mechanism under some conditions. The characteristics of each of these mechanisms are discussed, as well as their possible physiological functions. PMID- 2185658 TI - Specific properties of smooth muscle cells from different layers of rabbit myometrium. AB - Myometrial cells were isolated from rabbit uterine horns previously stripped of endometrium and oriented to submit the inner circular (CIRC) or the outer longitudinal (LONG) layer to enzyme dispersal. Cells from both layers attached to the culture dishes within 72 h, reached confluency around day 7, and exhibited different morphological patterns. Indirect immunofluorescence with antidesmin antibody revealed that both preparations were at least 80% smooth muscle. Similarly, electron microscopy confirmed the presence of microfilaments in both cell types and revealed characteristic ultrastructural features of smooth muscle cells. Cultured cells from CIRC appeared larger on the phase-contrast microscope, with a mean apparent surface area of 0.105 mm2 for circular and 0.067 mm2 for longitudinal cells. Adenylate cyclase activity in general was higher in circular than in longitudinal cells (P less than or equal to 0.05), but a significant beta adrenergic response to isoproterenol was observed only for longitudinal cells. This cell culture model is thus useful in defining the specific properties and functions of the different myometrial layers in the regulation of uterine contractility. PMID- 2185659 TI - Increased de novo purine synthesis by insulin through selective enzyme induction in primary cultured rat hepatocytes. AB - The proliferative effect of insulin on de novo purine synthesis and on the expression of various enzymes of purine metabolism were studied in primary cultured rat hepatocytes. Insulin greater than 1.5 x 10(-8) M increased DNA and de novo purine synthesis to 260-390 and 270-420%, respectively, 24 and 8 h after the administration. Insulin at 1.5 x 10(-7) M increased the specific activity of amidophosphoribosyltransferase (ATase) to 154-180%, hypoxanthine-guanine phosphoribosyltransferase to 129%, and adenine phosphoribosyltransferase (APRT) to 205%, in contrast to unchanged xanthine dehydrogenase at 80%. Enzyme induction was supported by the results of kinetic analysis and the inhibition of the insulin-induced increase in enzyme activities by protein synthesis inhibitors. Insulin increased ATP to 127% and decreased AMP, ADP, 5'-guanylic acid (GMP), and guanosine 5'-diphosphate (GDP), respectively, to 73, 69, 73, and 69%. Insulin increased adenylate energy charge from 0.83 to 0.90 without changing total feedback inhibitory potential on ATase. No obvious increase of 5-phosphoribosyl-1 pyrophosphate supply was suggested, although its apparent availability for purine ribonucleotide synthesis was increased to 208-245%, reflecting mainly induced APRT activity to 205%. It is concluded that hepatocyte proliferation by insulin, as evidenced by purine metabolism, is mediated by the selective gene activation of anabolic enzymes and increased ATP as the basis to activate multiple metabolic pathways without remarkable changes of substrate availability or feedback inhibition. PMID- 2185660 TI - Evolution of dexamethasone-induced insulin resistance in rats. AB - Glucocorticoids are known to cause insulin resistance and glucose intolerance. Although there have been many studies investigating the mechanism of this effect, several aspects remain to be clarified. The aim of this study was to investigate the evolution and sites of insulin resistance in dexamethasone-treated rats. To achieve this, chronically catheterized nonstressed rats had glucose kinetics measured during an oral glucose tolerance test by means of a double isotope technique. Studies were performed after 6, 48, or 96 h of dexamethasone administration (10 micrograms.rat-1.day-1) and were compared with control rats not treated with the steroid. Total hepatic glucose production (HGP) was increased in the 6-h (166 +/- 8.3, P less than 0.05) and 48-h (198 +/- 21, P less than 0.03) treated groups but not in the 96-h treated rats (140 +/- 8, P = 0.99) compared with the controls (141 +/- 8 mg/55 min). This increased HGP was despite the presence of higher insulin levels in the steroid-treated rats (1,220 +/- 115, P less than 0.09; 1,732 +/- 197, P less than 0.005; 1,567 +/- 107, P less than 0.001 in 6-, 48-, and 96-h treated rats, respectively, compared with 937 +/- 99 mU.l-1 x 55 min-1 in control rats). The metabolic clearance rate of glucose was higher in the dexamethasone-treated rats (200 +/- 14, P less than 0.07; 227 +/- 18, P less than 0.01; 227 +/- 17, P less than 0.01 in 6-, 48-, and 96-h groups, respectively, compared with 165 +/- 10 ml/55 min in control rats).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185661 TI - Role of 25-hydroxyvitamin D3 dose in determining rat 1,25-dihydroxyvitamin D3 production. AB - To understand the relationships among 1) the dose of 25-hydroxyvitamin D [25(OH)D] in vivo, 2) the activity of 1-hydroxylase in renal mitochondria, and 3) the production of 1,25-dihydroxyvitamin D [1,25(OH)2D] in vivo, we gave rats different chronic or acute doses of 25-hydroxyvitamin D3 [25(OH)D3]. We followed the metabolism of intracardially administered [25-hydroxy-26,27-methyl 3H]cholecalciferol [25(OH)[3H]D3] for 24 h before killing by measuring extracts of serum by chromatography. Specific activity of 1-hydroxylase in kidney was measured at death. In rats given 0-2,000 pmol 25(OH)D3 chronically by mouth, there was a dose-dependent decline in the percent of serum radioactivity made up of 1,25-dihydroxy-[26,27-methyl-3H]cholecalciferol [1,25(OH)2[3H]D3] as well as a decline in mitochondrial 1-hydroxylase, and these correlated significantly (r = 0.83, P less than 0.001). Serum %1,25(OH)2[3H]D3 in this experiment ranged from 0.8 to 42%. A small part of this range could be accounted for by a faster metabolic clearance rate (MCR) of 1,25(OH)2D3 from rats supplemented with 25(OH)D3 (MCR, 2.12 +/- 0.10 ml/min) compared with rats restricted in vitamin D (MCR, 0.94 +/- 0.06 ml/min, P less than 0.001). The activity of 1-hydroxylase was by far the major factor determining serum %1,25(OH)2[3H]D3. When different acute doses of 25(OH)D3 were given to rats with identical specific activities of 1 hydroxylase, the resulting 1,25(OH)2D3 concentrations in serum correlated with the 25(OH)D3 dose (r = 0.99, P less than 0.001). We conclude that the behavior of 1-hydroxylase in vivo is analogous to the classic behavior in vitro of an enzyme functioning below its Michaelis constant (Km). The amount of 1-hydroxylase present in renal mitochondria determines the fraction (not simply the quantity) of 25(OH)D metabolized to 1,25(OH)2D3 in vivo. PMID- 2185662 TI - [1-13C; methyl-2H3]methionine kinetics in humans: methionine conservation and cystine sparing. AB - Methionine (Met) conservation in healthy young adult men (4/diet group) was explored by supplying one of the following three L-amino acid based diets: 1) adequate Met but no cystine; 2) neither Met nor cystine; or 3) no Met but cystine supplementation. After 5 days, subjects received a continuous intravenous infusion of L-[1-13C; methyl-2H3]Met for 5 h while the diet was given as small isocaloric isonitrogenous meals. Estimates were made of rates of Met incorporation into protein synthesis (S) and release from body proteins (B), transmethylation (TM), remethylation of homocysteine (RM), and transsulfuration (TS). For the adequate Met diet, the rates were S = 24 +/- 2, B = 18 +/- 1, TM = 12.4 +/- 1.7, RM = 4.7 +/- 1.1, and TS = 7.6 +/- 0.6 (SE) mumol.kg-1.h-1. The sulfur amino acid-devoid diet significantly (P less than 0.05) reduced S, TM, RM, and TS. Supplementation of this diet with cystine reduced Met oxidation (P = 0.05). Therefore, two loci are quantitatively important regulatory points in Met conservation in vivo: 1) the distribution of Met between the pathways of protein anabolism and TM (Met locus) and 2) the distribution of homocysteine between RM and TS (homocysteine locus). PMID- 2185663 TI - D-[U-11C]glucose uptake and metabolism in the brain of insulin-dependent diabetic subjects. AB - We used D-[U-11C]glucose to evaluate transport and metabolism of glucose in the brain in eight nondiabetic and six insulin-dependent diabetes mellitus (IDDM) subjects. IDDM subjects were treated by continuous subcutaneous insulin infusion. Blood glucose was regulated by a Biostator-controlled glucose infusion during a constant insulin infusion. D-[U-11C]-glucose was injected for positron emission tomography studies during normoglycemia as well as during moderate hypoglycemia [arterial plasma glucose 2.74 +/- 0.14 in nondiabetic and 2.80 +/- 0.26 mmol/l (means +/- SE) in IDDM subjects]. Levels of free insulin were constant and similar in both groups. The tracer data were analyzed using a three-compartment model with a fixed correction for 11CO2 egression. During normoglycemia the influx rate constant (k1) and blood-brain glucose flux did not differ between the two groups. During hypoglycemia k1 increased significantly and similarly in both groups (from 0.061 +/- 0.007 to 0.090 +/- 0.006 in nondiabetic and from 0.061 +/- 0.006 to 0.093 +/- 0.013 ml.g-1.min-1 in IDDM subjects). During normoglycemia the tracer-calculated metabolism of glucose was higher in the whole brain in the nondiabetic than in the diabetic subjects (22.0 +/- 1.9 vs. 15.6 +/- 1.1 mumol.100 g-1.min-1, P less than 0.01). During hypoglycemia tracer-calculated metabolism was decreased by 40% in nondiabetic subjects and by 28% in diabetic subjects. The results indicate that uptake of glucose is normal, but some aspect of glucose metabolism is abnormal in a group of well-controlled IDDM subjects. PMID- 2185664 TI - Protein metabolic effects of a prolonged fast and hypocaloric refeeding. AB - In a study of the mechanism of adaptation to protein deficiency, 10 moderately obese women underwent a 3-wk fast followed by random allocation to a 1-wk refeeding regimen providing 80 g carbohydrate or protein. Protein metabolism was studied by means of nitrogen (N) balance, urinary 3-methylhistidine excretion, and postabsorptive plasma leucine flux using L-[1-13C]leucine infusions. After the 3-wk fast, plasma leucine flux and 3-methylhistidine excretion both decreased by 31% from control diet values (P less than 0.01), and N balance was -5.9 g/day. After protein refeeding, N balance was positive (+1.7 g/day, P less than 0.05) whereas leucine flux was unchanged from prolonged fasting values. After carbohydrate refeeding, N balance improved to -3.1 g N/day, whereas leucine flux decreased by a further 18% (P less than 0.05). Protein and carbohydrate refeeding were associated with further 23 and 31% reductions of 3-methylhistidine excretion compared with prolonged fasting (P less than 0.05). The results support the hypothesis that improved efficiency of protein retention in starvation is intimately associated with a decreased rate of protein turnover. PMID- 2185665 TI - Effect of hyperglucagonemia on hepatic glycogenolysis and gluconeogenesis after a prolonged fast. AB - The aim of this study was to determine if glucagon can stimulate hepatic glucose production in prolonged fasted (7 days) animals. Two protocols were used; in one ("hormone replacement"; n = 4), intraportal basal replacement amounts of insulin and glucagon were given during a somatostatin infusion, whereas, in the other ("glucagon excess"; n = 5) basal insulin was given along with somatostatin and excess glucagon. Plasma insulin levels were similar and constant throughout both protocols (6 +/- 1 microU/ml). The plasma glucagon was basal in the hormone replacement protocol (49 +/- 9 pg/ml) but rose from 46 +/- 7 to 448 +/- 35 pg/ml (P less than 0.05) in the other protocol. Plasma glucose levels and the rates of glucose production were unchanged during hormone replacement but rose from 100 +/ 5 to 199 +/- 28 mg/dl and from 1.5 +/- 0.1 to a peak of 5.6 +/- 0.2 mg.kg-1.min 1 at 15 min (P less than 0.05) and an eventual plateau of 2.7 +/- 0.2 mg.kg-1.min 1 (P less than 0.05) in response to glucagon excess. Because of the sluggish increase in gluconeogenic parameters, the early marked rise in glucose production was attributable to increased glycogenolysis. Eventually, however, the gluconeogenic rate rose, with net hepatic uptake of alanine increasing 50% and fractional alanine extraction doubling. Gluconeogenic efficiency and conversion increased in response to glucagon excess by 0.30 +/- 0.05 and 159 +/- 48%, respectively, although it should be noted that these parameters rose 0.15 +/- 0.06 and 150 +/- 49% in the hormone-replacement protocol. In conclusion, even after a prolonged fast physiological glucagon can cause hyperglycemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185666 TI - Validation of two-pool model for in vivo ketone body kinetics. AB - Previous studies have indicated that simultaneous infusions of two ketone body tracers ([13C]acetoacetate and [14C]beta-hydroxybutyrate) provide accurate estimates of exogenous ketone body inflow when an open two-pool model is employed. In the present studies, net hepatic ketone body production was determined from surgically placed arterial, portal venous, and hepatic venous catheters in conscious diabetic (n = 6) and 4-day fasted (n = 7) dogs. [13C]acetoacetate and [14C]beta-hydroxybutyrate were infused simultaneously, and ketone body production was calculated from either acetoacetate (AcAc) single isotope data, beta-hydroxybutyrate (beta-OHB) single-isotope data, the sum of individual fluxes, or the two-pool model. In fasted animals, both the AcAc single isotope calculation and the sum of individual fluxes overestimated net hepatic production by approximately 50% (P less than 0.05), whereas the beta-OHB single isotope calculation and the two-pool model gave accurate estimates. In the diabetic animals, the beta-OHB single-isotope calculation underestimated net hepatic production by approximately 30% (P less than 0.05). The sum of individual fluxes overestimated net hepatic production by approximately 46% (P less than 0.05), whereas both the AcAc single-isotope calculation and the two-pool model gave accurate estimates. In conclusion, single-isotope methods give erroneous estimates of net hepatic production of ketone bodies. In contrast, a two-pool model provided an accurate estimate of net hepatic production and thus appears to be suitable for determination of ketone body kinetics in humans. PMID- 2185667 TI - Structural and functional characteristics of muscle from diabetic rodent small intestine. AB - After 30 days of streptozotocin-induced diabetes, the small intestine from untreated diabetic, insulin-treated diabetic, and nondiabetic rodents was excised in toto and measured. Despite a net loss in body weight, the diabetic animals showed a near twofold increase in small intestinal weight. This was characterized by a 148% increase in mucosal mass as well as a 39% increase in intestinal smooth muscle mass (P less than 0.05, respectively). The diabetic intestine was significantly longer and had a greater diameter and surface area. Diabetes significantly increased mucosal mass per unit surface area but produced an insignificant decrease in smooth muscle mass per unit surface area. Insulin treatment of the diabetic animals prevented the increase in total mucosal mass and mucosal mass per unit surface area. Insulin treatment also prevented the increase in smooth muscle mass, but reduced smooth muscle mass per unit surface area to a level significantly less than that found in nondiabetic intestine. In vitro dose-response studies of circular and longitudinal small intestinal muscle from the diabetic animals showed normal tension development and sensitivity to both bethanechol chloride and physostigmine. These observations show that the diabetic state produces alterations in not only mucosal but also smooth muscle mass in the small intestine. However, despite these morphological changes, diabetic intestinal smooth muscle retains its sensitivity to cholinergic stimulation and its capacity for tension generation. PMID- 2185668 TI - Isolation and characterization of the canalicular membrane bile acid transport protein of rat liver. AB - The aim of this study was to isolate the Na(+)-independent bile acid transporter from rat canalicular plasma membranes by affinity chromatography. The affinity matrix used consisted of lysylcholic acid covalently linked to CH-Sepharose 4B, resulting in an anionic ligand essentially identical to glycocholic acid. The protein fraction, adsorbed and eluted from the affinity column, was markedly enriched in a 100-kDa band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) compared with the total membrane and membrane extract. The 100-kDa band, further purified by preparative SDS-PAGE, was electroeluted from excised gel fragments and used as an immunogen for antibody production in rabbits. The immune serum, but not preimmune serum, specifically recognized a single, 100-kDa polypeptide on one- and two-dimensional immunoblots of canalicular membranes. In contrast, no reactivity was observed with proteins in liver basolateral or ileal brush-border membranes. The 125I-labeled protein was immunoprecipitated from membrane extracts solubilized in NP-40 and was found to migrate with a pI of 5.3 on two-dimensional electrophoresis. The apparent molecular weight of the protein was reduced by 50% after deglycosylation with N glycanase. The 100-kDa protein was localized specifically and exclusively by immunocytochemical methods to the bile canalicular domain of the hepatocyte plasma membrane. Moreover, the immunoglobin G fraction prepared from the antiserum significantly inhibited taurocholate transport by canalicular membrane vesicles and decreased the covalent labeling of the 100-kDa protein by the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. Thus the isolation of a single 100-kDa protein by bile acid-affinity chromatography, as well as the inhibitory effects of antibodies directed against this polypeptide, provide further support for its role in the canalicular transport of bile acids. PMID- 2185669 TI - Cholecystectomy provides long-term symptom relief in patients with acalculous gallbladders. AB - Elective cholecystectomy was performed in 60 patients with biliary colic and acalculous gallbladders during a 5-year period. Gallbladder wall disease was significantly more common (p less than 0.01) in patients with acalculous gallbladders than in a similar symptomatic group with calculous gallbladders. Thirty-four of 43 patients (77%) available for long-term follow-up reported complete symptom relief after cholecystectomy. Preoperative ultrasonography, biliary scintigraphy, oral cholecystography, upper gastrointestinal series, and pathologic features of the gallbladder were equivocal in predicting long-term symptom relief. In patients with acalculous biliary colic, the best predictor of complete symptom relief is an adequate history of true biliary colic. PMID- 2185670 TI - Endoscopic retrograde cholangiopancreatography in the preoperative diagnosis of pancreatic neoplasms associated with cysts. AB - Neither computed tomography (CT) nor ultrasonography reliably distinguishes neoplastic from non-neoplastic pancreatic cysts. More invasive tests such as angiography or biopsy fail to differentiate these lesions in up to a third of patients. Because appropriate treatment differs greatly for these two classes of lesions, the clinician requires a more accurate means of confirming or excluding neoplasia. In an effort to refine the preoperative diagnosis of pancreatic cysts and evaluate the utility of endoscopic retrograde pancreatography (ERCP), we evaluated 11 patients with proven pancreatic neoplasia associated with cysts who underwent preoperative ERCP and CT scanning. Four patients had microcystic cystadenomas, two had a mucinous cystadenoma, one had a mucinous cystadenocarcinoma, and four had adenocarcinomas associated with cysts. CT identified a pancreatic cystic lesion in each patient. In all patients, ERCP showed either focal irregular narrowing, occlusion, or displacement of the main pancreatic duct at the corresponding location without the ductal changes of chronic pancreatitis. This helped to preoperatively differentiate these lesions from pseudocysts, hastening appropriate operation, obviating further testing and consultation, and aiding the intraoperative surgical strategy. PMID- 2185671 TI - [Treatment of malignant otitis externa]. AB - Though rare the malignant otitis externa must be borne in mind because in its precocious diagnosis is based the success of the management. Elderly people, diabetics and immunodepressed are especially exposed. The CAT is basic in order to detect the spreading of the process. The patient being admitted at a Medical center, the antibiotherapy started at once with Ceftazidine, 2 g every 12 hours via i.v. The exeresis of the e.e.ca proves sometimes necessary after control of the infection. This procedure assures the healing and prevent the recurrences some times seen. But when infection disappears owing to the success of the antibiotherapy in 2-3 weeks; the culture for Pseudomonas is negative 3 weeks later; and the previous CAT showed no spreading to the tympanal bone, the surgery must be discarded. The process is considered over when the culture for Pseudomonas aeruginosa is negative, but review of the patients is compulsory at least during half a year. PMID- 2185672 TI - [Open wound of the larynx caused by the horn of a bull]. AB - Open laryngeal traumas are seldom seen in E.N.T., specially those ones secondary to horn bull goring. We do a synthetized study with regard to report this original case treated in our Service. We justify the paper because of the intensity, the seriousness and the originality of the picture. PMID- 2185673 TI - Pressor responses to tracheal intubation after sublingual captopril. A pilot study. AB - The effect of sublingual captopril on the pressor response to intubation was studied in 40 patients. Captopril was used in one of two doses (12.5 mg and 25 mg) 25 minutes before tracheal intubation. Both doses were associated with a significant reduction in the pressor response to intubation (p less than 0.05) compared to placebo, but no significant difference existed between the two doses. Neither dose controlled changes in heart rate at intubation. Untoward hypotension occurred in the treatment groups. Caution is advised in the peri-operative use of angiotensin-converting enzyme inhibitors. PMID- 2185674 TI - Historical aspects of the International Federation of Associations of Anatomists. AB - The need for closer and personal scientific exchange among anatomists, histologists, embryologists, morphologists, anthropologists, veterinarians, dentists, biologists, and zoologists, and professionals of allied health sciences, and their interest in the uniformity of the technological language they all used in teaching and research, led a group of leaders in the field of Anatomy to found the International Federation of Associations of Anatomists (IFAA). PMID- 2185675 TI - Epidermoid cyst of the spleen presenting as a generalized peritonitis. AB - In this report we reviewed 159 cases of epidermoid cyst of the spleen reported since 1929 and we added one case of our own with a unique clinical presentation. In these cases, the patients' age at presentation ranged from newborn to 51 years, with a mean age of 17.7 years. Female-to-male ratio was 2.0 to 1.0. Patients with this lesion usually present with asymptomatic abdominal mass and/or abdominal pain. Only in rare reports has there been infection (4 cases) or rupture (4 cases) of the cyst. In our case, the patient presented with an acute surgical abdomen and diffuse peritonitis. As in three of the previously reported cases associated with infection, Salmonella group organisms were cultured from the cyst abscess. Splenectomy is the surgical treatment of choice and the initial antibiotic regime should include Salmonella coverage. PMID- 2185676 TI - Access to health care. American College of Physicians. PMID- 2185677 TI - Treatment of acute stroke. PMID- 2185678 TI - Granulocyte-macrophage colony-stimulating factor (GM-CSF), hypocalcemia, and hypomagnesemia. PMID- 2185679 TI - Surgery offers no more than medical treatment in the management of transient ischaemic attack. AB - This paper debates the motion that 'Surgery offers no more than medical treatment in the management of transient ischaemic attack' (TIA). The arguments in support of this motion are that surgical treatment has a high morbidity and mortality, and that even the investigation of patients by angiography prior to surgery entails a risk of stroke; that TIA is a marker of generalised vascular disease, and that medical treatment can reduce the incidence of stroke after TIA. The counter arguments are that TIA is associated with an increased risk of stroke and this risk can be reduced by surgery; that recent surgical results show an acceptable complication rate, and that modern methods of investigation permit accurate non-invasive assessment of patients at risk of stroke. PMID- 2185680 TI - Varicose vein surgery using a pneumatic tourniquet: reduced blood loss and improved cosmesis. AB - A prospective controlled randomised study has been performed of 100 consecutive patients undergoing varicose vein surgery. One group underwent saphenofemoral flush ligation and multiple lower leg avulsions with the leg exsanguinated with a Rhys-Davies cuff, and ischaemia maintained with a pneumatic tourniquet. The other group underwent identical surgery but with a 30 degree head down tilt only. Blood loss was significantly less (13.5 +/- 12 ml vs 133 +/- 78 ml; P less than 0.01) and postoperative cosmesis was significantly improved in patients in the tourniquet group. Operating time was similar (27 +/- 11 min vs 30 +/- 13 min) in the two groups. PMID- 2185681 TI - Meatal strictures after transurethral prostatectomy using latex or polyvinyl chloride three-way catheters. AB - Because latex rubber catheters have been implicated in urethral stricture formation, the incidence of urethral strictures following transurethral prostatectomy (TUP) and subsequent catheterisation with latex rubber or polyvinyl chloride catheters was compared. A total of 84 patients with benign prostatic hyperplasia (n = 71) or prostatic carcinoma (n = 13) underwent assessment of urethral diameter and subsequent internal urethrotomy prior to TUP. Following resection, 42 patients received three-way self-retaining latex rubber catheters and 42 received similar catheters made of PVC. Catheters were removed when the urine was clear (mean time = 3 days), and no patient required recatheterisation. Urinary flow was assessed in all patients at 6, 12 and 24 weeks after surgery, and diminution of flow with submeatal stricture formation was noted in one patient who had received a latex rubber catheter, and in one who had received a PVC catheter. In this study, the composition of the catheter had no bearing on subsequent stricture formation following TUP. PMID- 2185682 TI - Twelve years' experience of computer-aided diagnosis in a district general hospital. AB - This paper describes experience in a modern district general hospital with a small desktop system for computer-aided diagnosis of acute abdominal pain, over a 12-year period involving 5512 cases. When compared with a baseline year (1973) in which unaided performance was monitored, during an initial study period (1974-76) the diagnostic accuracy of junior staff rose by between 10 and 15%. This higher performance level was then maintained for a decade (1976-86) despite changes in staff. The perforation rate among appendicitis cases fell from 27% to 12.5%, accompanied by a smaller fall in negative laparotomy rates. The saving in surgical bednights devoted to acute abdominal pain was approximately 15%, and the notional cost of resources saved during the first 6 years of operation was 120,000 pounds. Other hospitals have shown--in the short term--benefits similar to those obtained at Airedale District General Hospital. The long-term benefits of the system at Airedale reinforce the conclusions of the earlier short-term trials that a comparable system should probably be offered to all DGHs in the UK, not as an exercise in 'artificial intelligence' but as an effective continuing stimulus to good clinical practice. PMID- 2185683 TI - The incidence of congenitally absent foot pulses. AB - The pedal pulses of 547 young healthy subjects were examined using digital palpation and a Doppler probe to determine the incidence of congenitally absent foot pulses. The posterior tibial (PT) pulse was absent in only one subject (0.18%), while the dorsalis pedis (DP) pulse was bilaterally absent in nine subjects (1.8%) and unilaterally absent in a further six subjects. The low incidence of congenital absence makes the clinical finding of an absent pedal pulse in later life a more significant marker of peripheral vascular disease than current surgical texts would have us believe. PMID- 2185684 TI - The role of ras and myc oncogenes in human solid tumours and their relevance in diagnosis and prognosis (review). AB - Advances in the field of oncogenes have produced a tool to investigate the different stages in multistep carcinogenesis. The role of the ras and myc gene families have been extensively investigated in the progression of carcinogenesis in a range of human solid tumours. This review critically analyses the data available on the role of these oncogenes in the six most common cancers worldwide, (i.e. cancer of the stomach, lung, breast, colon, cervix, and mouth and pharynx). In certain cases the incidence of aberrant gene expression and genetic alterations of the ras and myc gene families have been shown to be important in the progression of these cancers and may be of use as prognostic indicators. PMID- 2185685 TI - Effects of iron, copper and zinc on the activity of ribonucleotide reductase in normal and leukemic human lymphocytes. AB - The activity of ribonucleotide reductase (RR) extracted from normal and leukemic human lymphocytes was assessed. The activity of the enzyme was five times higher in leukemic cells than in normal lymphocytes. Fe and Cu stimulated and Zn inhibited RR activity in both types of cells. Zn also partially reduced the stimulatory effects of Fe and Cu. Deferoxamine (DFX) alone inhibited the activity of the enzyme and enhanced a similar inhibitory action of hydroxyurea (HU). In both cases the inhibitory effects were reversed by Fe and Cu, but not Zn. These findings suggest that: 1) Fe, Cu and Zn may modulate RR activity in vitro and their action is related and interdependent. 2) DFX alone may inhibit RR activity. 3) DFX enhances HU effect on leukemic cells. 4) The effects of both inhibitors may be modified by trace metals. PMID- 2185686 TI - C-myc, N-myc, N-ras, and c-erb-B: lack of amplification or rearrangement in human medullary thyroid carcinoma and a derivative cell line. AB - We investigated the copy number and possible rearrangement of the four protooncogenes, c-myc, N-myc, N-ras, and c-erb-B, in DNA from seven untreated primary cancers or metastases of medullary thyroid carcinoma and an established human medullary thyroid carcinoma cell line, TT, using the Southern blotting technique. The purpose of this study was two-fold: 1) to examine whether protooncogene perturbations in medullary thyroid carcinoma could be considered as a prognostic marker; and 2) to determine whether the protooncogenes could have a possible role in medullary thyroid tumorigenesis. Neither amplification nor rearrangement of the protooncogenes was detectable in the DNA from any tumor samples or in the cell line. Our results suggest that DNA-evident amplification and rearrangement of the c-myc, N-myc, N-ras, and c-erb-B oncogenes may not be mechanisms through which these oncogenes become activated in this malignancy. PMID- 2185687 TI - Circulating tumor markers in breast cancer (review). AB - The clinical application of circulating tumor markers remains a controversial subject in terms of useful methods and correct interpretation of findings. In particular and despite numerous investigations in the field, we do not have as yet specific or highly sensitive biological markers in breast cancer. Nevertheless, many oncologists often utilize circulating tumor markers in various phases of this malignancy to obtain additional information about disease extent and clinical course. For this reason, we have reviewed the present status of the most widely used serum tumor markers in this neoplasm. Both CEA and TPA are well known, but their organ specificity is not related to breast. Among novel biological markers identified by monoclonal antibodies, special attention has been devoted to circulating agents that are recognized by immunoreagents and that were obtained by immunization with breast-derived products. Both CA 15.3 and MCA are now being validated at the clinical level. From the present review it is clear that today we are still far from being able to make the diagnosis of breast cancer on the sole basis of laboratory findings. On the contrary, some of the available markers can be utilized as prognostic indicators of disease extent and treatment response. Their value greatly increases when combined with conventional diagnostic methods that can be prescribed on the basis of abnormal laboratory findings to confirm or rule out disease recurrence. PMID- 2185688 TI - Schedule-dependent effectiveness of ADM and multiple cycles of DDP on a murine reticulum sarcoma. AB - The therapeutic index of adriamycin (ADM) and cisplatin (DDP) combination versus repeated sequences of the more active drug (DDP) was investigated on a murine reticulum cell sarcoma of ovarian origin (M5) implanted i.m. in C57BL/6 mice. The antitumor efficacy of multiple cycles of DDP according to different regimens at a prefixed time (every 7 days) or at tumor regrowth was also evaluated. Our data demonstrate that the ADM-DDP combination did not improve the antitumoral efficacy of DDP as single agent, while repeated cycles of DDP led to a significant increase in the host life span. Differences in therapeutic effect were elicited by the two schedules: the regimen at a prefixed time showed a major effect on local tumor control, although the regimen at tumor regrowth was better tolerated. PMID- 2185689 TI - Amphotericin B: delivery systems. PMID- 2185690 TI - Penetration of ciprofloxacin into heart valves, myocardium, mediastinal fat, and sternal bone marrow in humans. AB - The penetration of ciprofloxacin into heart tissue (valve and myocardium), mediastinal fat, and sternal bone marrow was the object of a prospective nonrandomized study involving 36 patients undergoing mitral and/or aortic valve replacement. Patients were divided into two groups of 18. Group 1 patients were administered a single 400-mg intravenous dose of ciprofloxacin over a 1-h period. Group 2 patients received a 750-mg dose of ciprofloxacin orally every 12 h over the 48-h period preceding surgery. In this group, the last dose of ciprofloxacin consisted of an intravenous infusion of 400 mg. Concentrations of ciprofloxacin in plasma and tissue were assayed by high-performance liquid chromatography. Peak and trough levels in plasma were, respectively, 6.19 +/- 1.73 and 0.54 +/- 0.25 micrograms/ml in group 1 patients and 11.59 +/- 3.95 and 0.89 +/- 0.57 micrograms/ml in group 2 patients. Levels of ciprofloxacin in plasma remained significantly higher in group 2 than in group 1 until 12 h postinfusion (P less than 0.05). Concentrations of ciprofloxacin in heart valves and myocardia rose rapidly by 1 h postinfusion and remained greater than the MICs for usually susceptible pathogens for at least 5 h. Peak concentrations in myocardia were achieved by hour 1 and were 31.6 +/- 25.0 micrograms/g for group 1 and 21.8 +/- 13.0 micrograms/g for group 2. Peak concentrations in heart valves, achieved between hours 1 and 3, were 5.8 +/- 3.2 and 8.3 +/- 3.1 micrograms/g for groups 1 and 2, respectively. In both groups, peak concentrations in mediastinal fat were lower and achieved later. These were 3.1 +/- 3.8 micrograms/g in group 1 and 2.0 +/- 1.8 micrograms/gram in group 2 and were achieved between hours 3 and 5 and hours 1 and 3, respectively. In conclusion, the good diffusion of ciprofloxacin into heart tissue warrants its use for the treatment of bacterial endocarditis. On the other hand, low and delayed concentrations in mediastinal fat could limit its value as an antibiotic prophylactic agent in a cardiovascular surgical setting when administered immediately (less than 3 h) before surgery. PMID- 2185691 TI - Multiple-dose pharmacokinetics of concurrent oral ciprofloxacin and rifampin therapy in elderly patients. AB - The purpose of this clinical study was to investigate the influence of concomitant drug therapy with ciprofloxacin and rifampin on the individual pharmacokinetic profile of each agent in elderly patients. Twelve nursing home patients (age, 74 +/- 7 years), colonized with methicillin-resistant Staphylococcus aureus, were randomized to receive 14-day therapy with oral ciprofloxacin (750 mg every 12 h) (group A; n = 6) or ciprofloxacin (750 mg every 12 h) and oral rifampin (300 mg every 12 h) (group B; n = 6). Serial blood samples were obtained from 0 to 12 h following ciprofloxacin doses 1 and 13 and from 0 to 36 h after the last ciprofloxacin dose. No significant differences (P greater than 0.05) were found between or within groups in any pharmacokinetic parameter. The mean ciprofloxacin oral clearance values were 0.35 +/- 0.06, 0.41 +/- 0.15, and 0.38 +/- 0.11 liter/h per kg for doses 1, 13, and 28, respectively, in group A patients. The mean oral clearance values in group B patients for the respective doses were 0.53 +/- 0.36, 0.32 +/- 0.13, and 0.36 +/- 0.17 liter/h per kg. Likewise, no significant differences (P greater than 0.05) in rifampin pharmacokinetic parameters were found when compared with historical controls. These data suggest that ciprofloxacin and rifampin may be given concomitantly in standard clinical dosing regimens. The combination results in therapeutic levels of both drugs and appears to be safe for administration to elderly nursing home patients. PMID- 2185692 TI - Cross resistance to ciprofloxacin and other antimicrobial agents among clinical isolates of Acinetobacter calcoaceticus biovar anitratus. AB - Using an agar dilution assay, for 66 of 104 (63.5%) clinical isolates of Acinetobacter calcoaceticus biovar anitratus, the MIC of ciprofloxacin was greater than or equal to 1.0 micrograms/ml. Cross resistance was demonstrable to ciprofloxacin and gentamicin (P less than 0.001), amikacin (P less than 0.01), cefotaxime (P less than 0.001), azlocillin (P less than 0.001), ceftazidime (P less than 0.001), trimethoprim-sulfamethoxazole (P less than 0.001), and minocycline (P less than 0.05). The mean MIC of ciprofloxacin for drug susceptible isolates was consistently lower than that for resistant isolates; however, these differences were significant only for amikacin (P = 0.036). PMID- 2185693 TI - [A co-operative study on prophylactic effect of oral administration of high-dose amphotericin B syrup for systemic fungal infection in patients with hematological neoplasms. Chugoku-Shikoku Study Group of Mycosis with Hematologic Disease]. AB - The prophylactic effect of the oral administration of high-dose amphotericin B syrup for the systemic fungal infection was studied in 36 patients with hematological neoplasms. Twenty nine patients received 2,400 mg/day of Amphotericin B syrup for during the remission induction therapy. One patient received 1,200 mg/day, 3 received 800 mg/day and 3 received 400 mg/day of Amphotericin B syrup. The prophylactic effect was recognized in 24 of 36 patients, 66.7%. As adverse effects gastrointestinal symptoms such as nausea and vomiting, hypochloremia and hypopotassemia associated with hypochloremia was observed in one patient, respectively, however, they were all controllable. The blood levels of Amphotericin B in patients received 2,400 mg/day was 0.092 +/- 0.055 micrograms/ml (n = 40) on 7th day and 0.110 +/- 0.046 micrograms/ml (n = 21) on 28th day, respectively. The administration of high-dose of Amphotericin B syrup is expected not only for the prophylaxis but also for the treatment of the systemic fungal infection. PMID- 2185694 TI - [Clinical trial of KRN 8601 in patients with neutropenia induced by chemotherapy for lung cancer]. AB - The clinical trial of KRN 8601 was conducted in patients with neutropenia induced by chemotherapy for lung cancer. Thirty-six patients were treated with KRN 8601 subcutaneously for 14 days once daily at the dose of 50 or 100 micrograms/m2, and the effects were compared with the control phase without KRN 8601 treatment. Both the elevation of neutrophil count and shortened period of neutropenia were observed by the administration of KRN 8601. The efficacy rate was 75% (18/24) at 50 micrograms/m2 and 100% (10/10) at 100 micrograms/m2. A side effect observed was fever in one patients, and in 2 patients, abnormal GOT, GPT and LDH elevation were observed in each. We concluded that KRN 8601 was clinically effective and safe at the dose of 50 micrograms/m2 or 100 micrograms/m2 for neutropenia induced by chemotherapy for lung cancer. PMID- 2185695 TI - Metastatic Crohn's disease. Case report and review of the literature. AB - Metastatic Crohn's disease is an unusual granulomatous inflammation of the skin that is noncontiguous to the gastrointestinal tract. Our review of the English language literature shows that 23 cases of metastatic Crohn's disease have been published since its description in 1964. The skin lesions can be in the form of erythematous nodules, plaques, or ulcers, and the lower extremities are involved in half of the cases. We describe a 24-year-old woman with metastatic Crohn's disease. Ultrastructural examination revealed changes that were compatible with episodic endothelial cell injuries. Results of both direct and indirect immunofluorescence studies were negative. The possible role of T lymphocytes and macrophages in mediating this vascular damage is considered. PMID- 2185696 TI - Figurate and bullous eruption in association with breast carcinoma. AB - We describe a patient with two coexistent cutaneous eruptions: (1) trauma-induced bullae of the distal extremities and elbows and (2) multiple concentric gyrate lesions on the trunk and extremities, some of which became bullous. The gyrate lesions were stationary and nonpruritic. Biopsy of both types of lesions showed a subepidermal blister and a minimal inflammatory infiltrate. Direct immunofluorescence revealed linear deposition of IgG and C3 at the dermoepidermal junction and indirect immunofluorescence was negative. By immunoelectron microscopy, these immune deposits were localized to the lower lamina lucida. The eruption was not controlled despite high-dose (80 mg/d) oral administration of prednisone and required the addition of an oral administration of methotrexate (20 mg weekly). On further evaluation, an intraductal mammary carcinoma was detected. Following radiation therapy, the methotrexate and prednisone therapy were tapered without recurrence of the eruption during a follow-up period of 18 months. PMID- 2185697 TI - Fibrotic skin diseases. Clinical presentations, etiologic considerations, and treatment options. PMID- 2185698 TI - Sore throats. PMID- 2185699 TI - Haemophilus infection in cystic fibrosis. AB - Twenty seven patients with cystic fibrosis under the age of 12 years and 27 matched patients with asthma were followed up in a prospective study for one year. The isolation rate of non-capsulated strains of Haemophilus influenzae from cough swabs and sputum specimens taken at routine clinic visits every two months was significantly greater in cystic fibrosis than in asthma. Haemophilus para influenzae was equally common in both groups. During exacerbations the isolation rate of H influenzae in cystic fibrosis was significantly greater than at other times, whereas in asthma there was no significant difference. The distribution of biotypes of H influenzae and H parainfluenzae was similar in the two groups. In cystic fibrosis, biotype I was associated with exacerbations. Biotype V was more common than in previous studies, but was not associated with exacerbations. PMID- 2185700 TI - Rapid anticonvulsant monitoring in an epilepsy clinic. AB - The relevance of providing a rapid anticonvulsant monitoring service was assessed over a five year period at a paediatric epilepsy outpatient clinic. Altogether 481 drug assays were performed on 144 patients when considered clinically indicated. Drugs most frequently assayed were carbamazepine and sodium valproate, singly or in combination; sodium valproate, single or in combination; 90% of assays performed for phenytoin were from patients who were also taking another anticonvulsant. There were only six assays for ethosuximide and 10 for phenobarbitone. Physician's choice of drug dosage was recorded on a questionnaire before and after each assay result was known. Comprehensive patient details were analysed by a paediatric clinical pharmacologist, whose decision as to total daily anticonvulsant dosage was affected by knowledge of the drug concentration significantly less often than that of the clinicians for all the more commonly assayed drugs. There were a large number of drug assays that had no discernable clinical application. A more discriminating use of assays may both improve patient management and reduce considerably the number of anticonvulsant assays required. PMID- 2185701 TI - Influence of inspiratory flow rate upon the effect of a Turbuhaler. AB - The effect of a new breath actuated dry powder inhaler, the Turbuhaler, was found to be reduced at inhalations slower than 28 1/minute. This flow rate could be generated by virtually all children aged greater than or equal to 6 years, by 42 of 57 children less than 6 years (74%), and by six of 15 preschool children with acute wheeze (40%). PMID- 2185702 TI - Antimicrobial treatment for urinary tract infections. PMID- 2185703 TI - Neonatology--then and now. Plasma volume changes in the newborn (1958/59). PMID- 2185704 TI - In vivo tibial XFR measurement of bone lead. PMID- 2185705 TI - Passive smoking and the law. PMID- 2185706 TI - The pathobiology of ozone-induced damage. AB - Ozone remains one of the three most important air pollutants worldwide, yet little direct documented evidence of its genotoxicity exists. The interest in the pathology of ozone exposure and the molecular events that underlie its course stems from DNA damage caused by oxygen stress including hydroxyl radicals, superoxide, singlet oxygen, and hydrogen peroxide. Although the tissue damage associated with ozone inhalation occurs at both the conducting airway and the alveolus, the cellular and mechanistic processes underlying these events are less well understood. Ozone leads to the oxidative decomposition of polyunsaturated fatty acids. Ozone also depresses DNA replication in V79 Chinese hamster lung fibroblasts in a dose-dependent fashion (concentration, 1-10 ppm), which indicates that ozone or its reaction products may interact directly with DNA and inhibit replication. Ozone also linearizes circular DNA and induces ozone sensitive mutant and pneumocytes to repair its DNA. DNA adducts have been implicated in aging, cellular transformation, mutagenesis, carcinogenesis, and cell death; DNA adducts are products of free radical damage. These events are all common in ozone exposure. Finally, DNA-binding proteins are potent positive and negative regulators, enhancers, or silencers of gene expression. Part of their action may be related to their ability to initiate the binding sequence of DNA transcription proteins and thus form complexes. Alteration of DNA-binding sites by ozone adducts may effect mRNA transcription due to altered binding by DNA binding proteins. This altered transcription has been shown to effect growth factors involved in collagen and matrix regulation. The present review will address some of the complexities involved in ozone exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185707 TI - [Study of the inactivation of antibiotics by bacterial colonies]. AB - A procedure of bacteria application to disks from the colonies was used for determining antibiotic inactivation in the disks by the bacteria colonies after the disk direct contact with the colonies. Changes in the antibiotic activity in the disks were registered after incubation at 37 degrees C for 2 hours. It was shown that ampicillin resistant strains of E. coli K12 carrying R plasmids and strains of S. typhimurium and S. aureus inactivated the antibiotics in the disks and their population were homogenous in this respect. It is advisable to use the procedure in assaying drug resistance of bacterial populations. PMID- 2185708 TI - [Immobilization of antibiotics on a titanium surface]. AB - Immobilization of antibiotics on the surface of electrolytically oxidated titanium was tried. Transfer of the immobilized ampicillin into hardly soluble calcium ampicillate resulted in providing the coating with antimicrobial activity for 5 days. The quantity of the immobilized antibiotic determined polarographically amounted to 6.4.10(-3) mol per 1 m2 of the surface. PMID- 2185709 TI - [Effect of interferon on the course of experimental E coli-induced pyelonephritis]. AB - The effect of the type I interferon on the development and process of experimental pyelonephritis caused by E. coli was studied on mice weighing 12 to 14 g. Interferon was administered intraperitoneally in a dose of 1000 units on days 3 and 7 of the disease. It was shown that the administration of the type I interferon to the mice with experimental pyelonephritis promoted rapid elimination of bacteria from the kidneys, prevented their penetration to the contralateral (intact) kidney, prevented marked macro- and microscopic damages in the kidneys, lowered the intensity of the inflammatory reaction, and increased the phagocytic activity of neutrophils and the number of the E-rosette-forming lymphocytes in the thymus. The data provided experimental grounding for clinical trials of interferon preparations in treatment of bacterial pyelonephritis. PMID- 2185710 TI - [Cephalosporins of the 1980s. New aminothiazolyloxyimino-cephalosporins and their sulfoxides]. PMID- 2185711 TI - [Cephalosporins of the 1980s. Aminothiazolylcephalosporins, non-glycine and phenylglycine cephalosporins, aminocephalosporins, cefamines, carbacephems and oxacephems]. PMID- 2185712 TI - Recovery of exponentially growing cultures of Klebsiella pneumoniae NCIB 418 after heat shocks. AB - Exponentially growing cultures of Klebsiella pneumoniae were subjected to heat shocks in the superoptimal and supermaximal temperature ranges for growth on glucose in a defined mineral salts medium. Transitory changes in the specific growth rate constant during recovery were evident. The response was heat shock temperature and exposure time dependent. Cell viability determinations, based on colony counts, indicated complete recovery from heat treatments at superoptimal temperatures. In contrast, at supermaximal temperatures, discrepancies in colony counts on different agars were observed. The kinetic response of the specific growth rate constant after a heat shock at supermaximal temperatures is explained by segregation within the bacterial population. PMID- 2185713 TI - Clinical diagnosis by nuclear magnetic resonance spectroscopy. If not now, when? AB - Nuclear magnetic resonance spectroscopy is the epitome of the high-technology, expensive diagnostic method. Extrapolation from a limited number of patient examinations and from experiments in animal models predicts a bright future for the method. However, several barriers block widespread clinical application in the near future; technical difficulties still exist but they seem to be resolvable in due course. A more serious problem is the absence of an adequate database from which to interpret the vast array of information produced by nuclear magnetic resonance. The necessary understanding of the pathologic biochemistry of disease will be frustratingly slow to appear as will the routine clinical use of magnetic resonance spectroscopy. The critical need for improved diagnostic methods will stimulate experimentation to resolve these problems. PMID- 2185714 TI - Respiratory cryptosporidiosis in a patient with malignant lymphoma. Report of a case and review of the literature. AB - Respiratory cryptosporidiosis is a rare complication of intestinal infection by cryptosporidia, with only six cases reported (to our knowledge) since its first description in 1983. We report the first case of respiratory cryptosporidiosis recognized at the National Institutes of Health, Bethesda, Md. An antemortem diagnosis was made based on recognition of acid-fast cryptosporidia in an induced sputum specimen obtained from a 64-year-old woman with malignant lymphoma and an associated profound immunodeficiency. Autopsy confirmed the presence of cryptosporidia along the apical aspect of the respiratory epithelium lining the trachea, bronchi, and bronchioles. Cryptosporidia were also identified in the duodenum and gallbladder. Immunohistochemical staining of the paraffin-embedded autopsy lung sections using a monoclonal antibody verified the diagnosis of cryptosporidiosis. Review of our case and the literature suggests that respiratory cryptosporidiosis is characterized by a chronic tracheitis, bronchitis, and bronchiolitis but generally does not cause severe pulmonary dysfunction. PMID- 2185715 TI - Adult variant of congenital mesoblastic nephroma. AB - Congenital mesoblastic nephroma is a relatively rare tumor predominantly of childhood. Occurrence in adults is exceedingly rare and, to my knowledge, only two cases have been reported to date. This article pertains to a mesoblastic nephroma in a 41-year-old woman. The tumor was composed mainly of compact fibrocollagenous elements interspersed with areas containing immature tubules and occasionally glomeruloid structures. There was no evidence of capsular or renal invasion or cytological malignant features. It has been postulated that this neoplasm may represent a form of mature Wilms' tumor with a benign clinical course. PMID- 2185716 TI - Chondroma of the tongue. Report of a case and a consideration of the histogenesis of such lesions. AB - Chondroma of the tongue is a very rare condition. We describe a case that demonstrates unusual features in terms of its location in the tongue and the presence of noncartilaginous elements. Of the various hypotheses concerning the pathogenesis of lingual chondromas, it seems most likely that they are truly neoplasms (or hamartomas) of mesenchymal tissue that manifest metaplastic features. PMID- 2185717 TI - Transgenic animals. PMID- 2185718 TI - Isolated complete denervation of the flexor pollicis longus. AB - Isolated complete denervation of the flexor pollicis documented by electromyography has not been reported. We report a healthy 26-year-old man who sustained a gunshot wound at the base of his left index finger. He reported ipsilateral flexor pollicis longus (FPL) paralysis one week later, after undergoing surgical exploration of the radial digital artery and nerve supplying the left index finger under axillary block anesthesia. Forearm pronation and distal interphalangeal flexion of the second through fifth digits were normal. Electromyographic findings revealed complete isolated denervation of the FPL. This represents a lesion involving the branch or branches of the anterior interosseous nerve to the FPL. The etiology was postulated to be either a direct injury secondary to intravenous catheter placement or an unusual presentation of neuralgic amyotrophy. PMID- 2185719 TI - Congenital carpal tunnel syndrome: case report of autosomal dominant inheritance and review of the literature. AB - Carpal tunnel syndrome (CTS) is unusual in childhood, and familial occurrence has been reported infrequently. A case of CTS in a seven-year-old boy, associated with abnormal thickening of the transverse carpal ligament and aplasia of the median nerve distal to this ligament, is described. Clinical, electrodiagnostic, and surgical findings are presented: all were consistent with absence of the median nerve distal to the transverse carpal ligament. Family history of CTS was positive in a pattern consistent with autosomal dominant transmission in three generations. Thickening of the transverse carpal ligament has been described, although infrequently, in childhood and familial CTS. Aplasia of the median nerve distally has not been reported in association with this anatomic abnormality. Case reports of familial CTS are reviewed, and other congenital anomalies which should be considered in the differential diagnosis of CTS in children and adults are discussed. PMID- 2185720 TI - Cerebrogenic cardiac arrhythmias. Cerebral electrocardiographic influences and their role in sudden death. AB - Electrocardiographic repolarization changes, comprising QT prolongation, T-wave flattening or inversion, and ST-segment alterations, are most commonly seen after subarachnoid and intracerebral hemorrhage, but may occur in other neurologic conditions. They may presage arrhythmias. The effects likely are mediated by the sympathetic nervous system. Cerebral arrhythmogenesis may underlie sudden death in both normal and epileptic populations. Experimental evidence suggests that the insula has a cardiac chronotropic organization, and may be involved in the genesis of arrhythmias seen in epilepsy or after cerebral hemorrhage or stroke. PMID- 2185721 TI - Vaccine-associated paralytic poliomyelitis. Regional case series and review. AB - We present 10 cases of vaccine-associated paralytic poliomyelitis from Washington State to better acquaint physicians with the signs and symptoms of this condition. Diagnosis may be delayed, and milder cases may be overlooked, owing to the unfamiliarity of physicians with the condition. Based on these 10 cases, a rate of 6.4 cases (recipient plus contact) per million live births is estimated for the period 1966 through 1988 in Washington. This rate is higher than calculated for the nation as a whole. The explantation for this difference is unknown, although several possibilities exist, including case clustering. PMID- 2185722 TI - Scheie Eye Institute namesake dies at age 80 years. PMID- 2185723 TI - A randomized placebo-controlled trial of cysteamine eye drops in nephropathic cystinosis. AB - Eighteen patients with nephropathic cystinosis who were younger than 42 months and 11 patients 4 to 31 years of age were entered into a double-masked, randomized, placebo-controlled trial of topical cysteamine eye drops between November 1985 and September 1989. Eight of the younger patients and 2 of the older patients showed marked clearing of corneal crystals in one eye compared with the fellow eye. When the code was broken, all 10 patients were found to have received cysteamine eye drops in the improved eye. Of the remaining 19 patients 4 were unavailable for follow-up. In 15 patients no marked difference was noted between the two eyes. Eight have presumably been in the protocol for too short a time and several have been poor compliers with the therapy. These results not only demonstrate the potential for primary prevention of corneal crystal deposition but also, for the first time, offer the possibility of reversing the corneal complications of cystinosis in older patients. PMID- 2185724 TI - Immunocytochemical localization of gentamicin in the rabbit retina following intravitreal injection. AB - The localization of gentamicin in the retina after a single intravitreal injection in the rabbit eye was examined by indirect immunofluorescent staining with goat antigentamicin antiserum. Eight hours after the injection of 400 micrograms of gentamicin, staining was observed in the ganglion cell layer, the inner plexiform layer, the inner nuclear layer, and the photoreceptors. By 12 hours, the staining was also observed in the retinal pigment epithelium. Howeever, by 24 hours the staining was predominantly found in the retinal pigment epithelium and choriocapillaris, and only occasional staining was seen scattered in the neurosensory retina. At 36 to 48 hours, the labeling was confined to the retinal pigment epithelium and choriocapillaris. Electron microscopy confirmed the cytoplasmic localization of gentamicin in the retina. PMID- 2185725 TI - A new self-sealing needle for iris suture fixation. AB - We adapted a 27-gauge, 0.75-in needle for the placement of iris fixation sutures. The needle requires neither the formation of a paracentesis nor a sclerotomy site. Additionally, the self-sealing nature of the needle tract eliminates the need for closure of the entry site. We have found this instrument to be helpful in the rapid, atraumatic placement of iris fixation sutures. PMID- 2185726 TI - Nutrition advice for athletes. AB - The authors discuss athletes' nutritional needs across a broad range of sports, and explain how the sports dietitian assists athletes with the practical aspects of sports nutrition. A general discussion of the various food components, their interactions and requirements, provides useful dietary information. The 'Guidelines for sensible weight loss programme' would be useful for most weight conscious patients. PMID- 2185727 TI - The role of nutritional medicine in general practice. AB - Over the past decade there has been a virtual explosion in information in the medical and scientific literature relating nutrition to disease. Nutritional factors have been documented in the aetiology of most of our degenerative diseases including diabetes, arthritis, coronary artery disease, stroke and cancer. A change in diet and the appropriate use of nutrients reduce the risk of disease. PMID- 2185728 TI - The doctors in Shakespeare's plays. Part two. AB - In the second part of his article about Shakespeare's references to the medical profession, the author selects quotes that show some positive and negative images of the doctors of the day. PMID- 2185729 TI - Assessing the benefits and risks of drugs. The example of NSAIDs. AB - Although NSAIDs are among the most familiar drugs to general practitioners, an assessment of their likely benefits and risks should be made for every prescription. The most important risk factors for 'predictable' reactions are old age and a history of peptic ulcer, cardiovascular and renal disease, and asthma. The presence of uncomplicated peptic ulcer is not an absolute contraindication to an NSAID so long as the use of the drug is necessary. These drugs reduce symptoms rather than modify diseases and patients should be involved in the prescribing decision and be empowered to stop treatment. PMID- 2185730 TI - Rotation flap. PMID- 2185731 TI - Manipulative medicine. PMID- 2185732 TI - Breast cancer cytogenetics and beyond. AB - It is hypothesized that cancers arise as a result of genetic or chromosomal alteration. Evidence for this is provided by the leukaemias and lymphomas in which cytogenetic studies are of established value in diagnosis, classification and follow-up. In contrast, the cytogenetic study of all solid tumours, including breast carcinoma, is in its infancy. However, cytogenetic studies indicate that clonal structural alterations do occur, affecting several loci on a number of chromosomes. Molecular studies provide further evidence of recurring chromosomal breakpoints in breast cancer. This paper reviews the chromosomal rearrangements observed to date and discusses their relevance to the biology of breast cancer. PMID- 2185733 TI - A view of the development of intestinal suture. Part II. Principles and techniques. AB - During the 19th century, the principles of suturing and operating upon the bowel were developed. Lembert published his technique, emphasizing the importance of the serosa in 1826. This brought about sudden transition from the ancient methods of intestinal surgery. Considerable controversy followed. Dieffenbach reported the first clinical success with this suture in 1836. Lister introduced aseptic sutures and the principles of antisepsis to the intestine which allowed the subsequent developments. The importance of the submucosa in anchoring a stitch, so that divided surfaces could stay opposed, was drawn to surgeons' attention by Gross and by Halsted. Mall described the histologic changes and pointed out that necrosis would occur if sutures were too close or too tight. More than 200 modifications were described by the beginning of the 20th century. During the 1950s, everting suture was compared with inverting anastomoses, and the safety of this method was realized. PMID- 2185734 TI - Origins of the Urological Society of Australasia. AB - The origins of urology as a specialty and the organization of urologists is outlined. This coincides with the 50th anniversary of the Urological Society of Australasia (USA). Biographies of the first five presidents of the USA illustrate some characteristics of the foundation members. PMID- 2185735 TI - Hepatocolonic vagrancy: wandering liver with colonic abnormalities. AB - Abnormalities of hepatic fixation resulting in excessive mobility in a transverse plane are uncommonly encountered. The unusual incidental finding of a freely mobile liver and spleen in a patient presenting with sigmoid volvulus is reported. At laparotomy, the inferior aspect of the right hemidiaphragm was smoothly peritonealized, without evidence of coronary or triangular ligaments. It is postulated that this abnormal hepatic mobility reflects persistence of the primitive ventral mesogastrium. To the authors' knowledge, this unusual condition has not previously been recognized. The literature relating to wandering liver is reviewed and four other cases are presented. An invariable association of persisting ventral mesogastrium with abnormalities in colonic anatomy (hepatocolonic vagrancy) is described. PMID- 2185736 TI - The first Australian case description of anorexia nervosa. AB - To the best of our knowledge, H.E. Astles was the first Australian physician who, in a lecture in 1882, paid explicit attention to the illness of anorexia nervosa. We reproduce his paper because of its historical value, which we underline in our comments. PMID- 2185737 TI - Psychiatry and the frontal lobes. AB - The frontal lobes of the brain have long been regarded as enigmatic in their function and perhaps should be considered even more so in states of dysfunction. Observed associations between structural lesions and psychiatric symptoms and the demonstration of disturbed function and morphology in the frontal lobes of individuals suffering from major psychiatric disorders have led to increased interest in this brain area. Psychiatrists have been particularly concerned with seeking the aetiogenesis of common diagnostic entities and this article attempts to synthesize the available facts. A brief overview of relevant biological data precedes a description of methods of neuropsychological testing and the clinical features arising from frontal lobe damage. A discussion of the role of the frontal lobes in some aspects of personality function follows. Neuropsychiatric features associated with known frontal lobe pathology are described, prefacing a discussion of those psychiatric conditions where an aetiological role for frontal lobe dysfunction has been proposed. PMID- 2185738 TI - The first 200 years of Australian psychiatry. PMID- 2185739 TI - A phenomenology of jealousy. AB - Phenomenology is the study of conscious mental events. That it is conscious events requires emphasis, particularly at this moment in the historical development of psychiatry when we are still emerging from the thrall of psychodynamic causalities, said to lie in unconscious and unknowable realms, and are in danger of descending into another mythology of extra conscious mechanisms compounded from neurobiological speculations. PMID- 2185741 TI - Anti-insulin antiserum increases inositol phosphate accumulation in rat pancreatic islets. AB - The role of insulin in modulating phosphoinositide breakdown and accumulation of inositol phosphates was investigated in isolated rat pancreatic islets by using GPAIS (guinea-pig anti-insulin antiserum) that neutralizes effects of insulin in the medium. At either 3.0 mM- or 16.7 mM-glucose or 3.0 mM-glucose plus 10 microM arecaidine propargyl ester (muscarinic receptor agonist), GPAIS (but not control serum) was able to increase InsP2 and InsP3, but not InsP, in myo-[3H] inositol prelabelled islets. The effect of GPAIS on 3H incorporation into InsP3 was dose dependent, with a half-maximal effect at a concentration able to bind 4004 +/- 163 microunits of insulin. A specific mass assay of the biologically relevant isomer Ins (1,4,5)P3 revealed a huge increase (greater than 3-folf). Formation of PtdIns, PtdInsP and PtdInsP2 was not affected by GPAIS. This is indirect evidence for an effect of insulin on inositide metabolism, and therefore endogenously released insulin may have led to an underestimation in earlier studies of effects of insulinotropic substances on inositol phosphate accumulation. PMID- 2185740 TI - Nitrogen metabolism in liver: structural and functional organization and physiological relevance. PMID- 2185742 TI - Glucose-induced activation of pyruvate dehydrogenase in isolated rat pancreatic islets. AB - 1. Rat pancreatic islets were isolated and then maintained in culture for 2-4 days before being incubated in groups of 100 in the presence of different glucose (0-20 mM) or CaCl2 (1.2-4.2 mM) concentrations, or with uncoupler. 2. Increases in extracellular glucose concentration resulted in increases in the amount of active, non-phosphorylated, pyruvate dehydrogenase in the islets, with half maximal effects around 5-6 mM-glucose. Increasing extracellular glucose from 3 to 20 mM resulted in a 4-6-fold activation of pyruvate dehydrogenase within 2 min. 3. The total enzyme activity was unchanged, and averaged 0.4 m-unit/100 islets at 37 degrees C. 4. These changes in active pyruvate dehydrogenase were broadly similar to changes in insulin secretion by the islets. 5. Increasing extracellular Ca2+ or adding uncoupler also activated pyruvate dehydrogenase to a similar degree, but only the former was associated with increased insulin secretion. PMID- 2185743 TI - Thiol-dependent metallo-endopeptidase characteristics of Pz-peptidase in rat and rabbit. AB - Pz-peptidase was purified from rat testis and rabbit muscle. Zinc was detectable in the rat enzyme. The activity of the enzyme from both species was slowly but completely abolished by EDTA and restored by Zn2+. Free thiol groups were also important for the catalytic activity of rat Pz-peptidase, as previously reported for the rabbit enzyme. We conclude that in both species Pz-peptidase has the characteristics of a thiol-dependent metallo-endopeptidase. PMID- 2185744 TI - Insulin-induced phospho-oligosaccharide stimulates amino acid transport in isolated rat hepatocytes. AB - The ability of the insulin-induced phospho-oligosaccharide to stimulate amino acid transport was studied in isolated rat hepatocytes. At low alpha aminoisobutyric acid concentrations (0.1 mM), both 100 nM-insulin and 10 microM phospho-oligosaccharide doubled amino acid uptake after 2 h of incubation. This stimulation was prevented by 0.1 mM-cycloheximide or 5 micrograms of actinomycin D/ml, indicating that the phospho-oligosaccharide, like insulin, was acting via the synthesis of a high-affinity transport component. The effects of the phospho oligosaccharide and of insulin were blocked by Ins2P (2.5 mM), but not by myo inositol, inositol hexaphosphoric acid or several monosaccharides such as mannose, glucosamine and galactose. Both the temporal effect on amino acid entry and the extent of stimulation of this process by the phospho-oligosaccharide indicate that this molecule mimics, and may mediate, some of the long-term actions of insulin. However, the effects of phospho-oligosaccharide and insulin were not exactly the same, since the effect of insulin, but not of the phospho oligosaccharide, was additive with that of glucagon. PMID- 2185745 TI - Metabolism of hexacosatetraenoic acid (C26:4,n-6) in immature rat brain. AB - Rat brain was recently found to contain polyenoic very-long-chain fatty acids (VLCFA) belonging to the n-3 and n-6 series with four, five and six double bonds and even-carbon chain lengths from 24 to 38 [Robinson, Johnson & Poulos (1990) Biochem. J. 265, 763-767]. In the present paper, the metabolism in vivo of hexacosatetraenoic acid (C26:4,n-6) was studied in neonatal rat brain. Rats were injected intracerebrally with [1-14C]C26:4,n-6 and the labelled metabolites were examined after 4 h. Radioactivity was detected mainly in non-esterified fatty acids, with smaller amounts in other neutral lipids and phospholipids. Radiolabelled fatty acid products included C28-36 tetraenoic and C26-28 pentaenoic VLCFA formed by elongation and desaturation of the substrate, and C14 24 saturated, C16-24 monoenoic, C18-24 dienoic, C18-22 trienoic and C20-24 tetraenoic fatty acids formed from released [1-14C]acetate either by synthesis de novo or by elongation of endogenous fatty acids. The data suggest that polyenoic VLCFA are synthesized in brain from shorter-chain precursor fatty acids and undergo beta-oxidation. PMID- 2185746 TI - Processing of recombination intermediates in vitro. AB - Genetic recombination involves the exchange of genetic material between chromosomes to produce new assortments of alleles. As such, it affects one of the most fundamental and important components of heredity--the genome itself. To understand the molecular basis of recombination, efforts have been directed to try to determine how simple organisms recombine their DNA. One approach involves the development of in vitro systems in which recombination reactions can be studied using purified enzymes. Detailed studies of these systems, using enzymes isolated from bacteria and bacterial viruses, indicate the formation of unique protein-DNA complexes. The structure of the DNA within these complexes has important consequences for the subsequent formation of recombinant products. PMID- 2185747 TI - Unbalanced transmethylation and the perturbation of the differentiated state leading to cancer. AB - It is proposed that the perturbation of the differentiated state in cancer is related to alterations in DNA methylation as well as to alterations in methylation of other cellular molecules, leading to an imbalance in global cellular methylation. It is hypothesized that the global imbalance in methylation is reflected in the enhanced levels of transmethylation seen in many cancer cell types as well as in a number of undermethylated molecules. PMID- 2185748 TI - Formation of a gradient of the Drosophila dorsal morphogen by differential nuclear localisation. PMID- 2185749 TI - YAC power. PMID- 2185750 TI - The fission yeast, Schizosaccharomyces pombe. PMID- 2185751 TI - The discovery (or rediscovery?) of the phenomenon of premature chromosome condensation. PMID- 2185753 TI - Augmented excretion of procathepsin L of a fos-transferred highly metastatic rat cell line. AB - We previously reported that v-fos transfer to a src-transformed rat 3Y1 cell line (SR-3Y1-2) enhanced lung metastasis accompanied with an increase in invasiveness. When analyzing factors relating to the high invasiveness, with special reference to typical lysosomal proteases (cathepsins), involving degradation of stroma, we found that the excretion of procathepsin L was significantly larger in the fos transferred highly metastatic cell line (fos-SR-3Y1-202) than that in the recipient cell lines. The cathepsin D-induced enzyme activity of the excreted procathepsin L in fos-SR-3Y1-202 was about 4 and 13 fold that of SR-3Y1-2 and 3Y1, respectively. The increase in the excretion of procathepsin L from fos-SR 3Y1-202 may play a role in the high invasiveness induced by transfer with the v fos oncogene. PMID- 2185752 TI - Endothelin-1 stimulates arachidonate 15-lipoxygenase activity and oxygen radical formation in the rat distal lung. AB - We investigated the effects of intravenous bolus of endothelin-1 on the metabolism of eicosanoids and oxygen radicals in the distal lung unit of the rat. Intravenous bolus of endothelin-1 caused a significant increase in 15 hydroxyeicosatetraenoic acid of bronchoalveolar lavage fluid and oxygen radicals produced by the bronchoalveolar cells. Endothelin-1 exhibited a stimulatory effect on the 15-lipoxygenase activity in the lung homogenate. Thus, endothelin-1 may contribute to the inflammatory and hyperreactive process of lungs, by enhancing the release of 15-hydroxyeicosatetraenoic acid and oxygen radicals in the distal lung unit. PMID- 2185754 TI - Use of an immobilized enzyme and specific antibodies to analyse the accessibility and role of histone tails in chromatin structure. AB - Using limited proteolysis with subtilisin bound to collagen membranes, the degradation of the histone proteins revealed by specific antibodies was correlated to changes in chromatin conformation and condensation monitored by circular dichroism and electric birefringence. This new approach allows us to detect for the first time a hierarchy of histone tails cleavages. The terminal domains of H1, the NH2-terminal tail of H3 and the carboxy-terminal ends of histones H2A and H2B were found to be cleaved already at the early stages of proteolysis and this led to a decondensation of polynucleosomal chains. Thereafter the C-terminal part of H3 and both NH2-terminal regions of H2A and H2B became rapidly cleaved, resulting in relative reorientation of swinging nucleosomes or partially unfolded segments. Unexpectedly, this removal of tails of H1, H2B, H2A and H3 is not accompanied by significant changes in DNA-protein interactions resulting in free-oriented DNA. This might suggest that histone histone interactions play a central role in stabilizing the solenoid. PMID- 2185756 TI - Chemical nuclease activity of 5-phenyl-1,10-phenanthroline-copper ion detects intermediates in transcription initiation by E. Coli RNA polymerase. AB - The nuclease activity of the copper complex of 5-phenyl-1,10-phenanthroline (5 phi-OP-Cu) detects conformational changes in the lac UV-5 promoter caused by E. Coli RNA polymerase. The template strand in melted regions of initiation complexes upstream of the site of nucleotide triphosphate incorporation is very reactive. In open and elongation complexes, downstream scission sites (e.g. +4 and +5 for the open complex) on both strands are observed. The patterns of both downstream cutting sites suggest an atypical double helix at the leading edge of the transcription bubble. PMID- 2185755 TI - High valent iron oxo intermediates might be involved during activation of ribonucleotide reductase: single oxygen atom donors generate the tyrosyl radical. AB - The active form of protein B2, the small subunit of ribonucleotide reductase from E. Coli, contains a binuclear non heme iron center and a tyrosyl radical. MetB2 is an inactive form that lacks the radical but retains the Fe(III) center. We earlier proposed that the function of the iron center was to catalyze the one electron oxidation of the tyrosine residue from metB2 by dioxygen. We now report that incubation of metB2 with single oxygen atom donors, hydrogen peroxide, 3 chloroperoxybenzoic acid, monoperoxophtalate and 2-iodosobenzoate, also results in the formation of the tyrosyl radical, as monitored by UV-visible and EPR spectroscopy. A mechanism of reductive activation of dioxygen by the binuclear non heme iron center involving iron-oxo intermediates is proposed. PMID- 2185757 TI - Identification of mitotic (CDC2) and interphase histone H1 kinases by nondenaturing gel electrophoresis and peptide assays. AB - A new method of nondenaturing gel electrophoresis and a specific peptide based assay were used to study the histone kinases in mitotic and interphase mouse fibroblasts. The gels resolved four activities, one of which was shown to be the mitotic (CDC2) H1 kinase by virtue of its antigenicity. A new peptide substrate for the CDC2 kinase was phosphorylated by both S-phase and mitotic cell extracts and reacted with two protein kinases in the gels. Since the interphase enzyme did not react with the antibody, the results suggest that it is either a "masked" form of CDC2 or a second enzyme, functionally related to CDC2, which is responsible for the interphase phosphorylation of H1. PMID- 2185758 TI - Cloning and expression of pectin lyase gene from Erwinia carotovora in Escherichia coli. AB - A pectin lyase (PNL; EC 4.2.2.10) gene of Erwinia carotovora Er was cloned and expressed in Escherichia coli. The analysis of the nucleotide sequence of the 0.6 kb StuI-EcoRI fragment, which was hybridized with the mixed oligonucleotide probe for PNL gene, revealed the presence of an open reading frame (0RF) and correlated exactly with the known N-terminal 18 amino acid sequence of PNL. When a plasmid pTN2159, which has a BamHI-EcoRI fragment containing this ORF, was introduced into E. coli JM109, PNL was not expressed. When a tac-promoter was inserted in front of the ORF, PNL was efficiently expressed in E. coli. Synthesis of PNL by E. coli was also confirmed by immunoblot analysis. PMID- 2185759 TI - New approach for the in vitro evaluation of antacids. AB - Evidence is given that the in vitro evaluation of antacids has been incomplete, not regarding physiopathological conditions. As a consequence arbitrary antacid potency classifications were introduced and in clinical practice high dosages of antacid drugs were prescribed. The main reason is that the in vitro evaluation procedures used did not take into account the actual conditions of gastric acid secretion. The proposed methods allow to assess antacid activity under conditions similar to those during gastric secretion. "Pharmacologically", the capacity of binding H+ ions in acid milieu can be quantified and the antacid mechanism can be characterized. "Therapeutical efficacy" might be analysed under acid conditions taking into account gastric intraluminal flux variations by using the "artificial stomach" model. This procedure also allows to evaluate the influence of gastric protein content on antacid activity and to simulate the actual gastric conditions by using human gastric juice as gastric content and as simulated "secretion". The antacid-induced resistance to acidification largely corresponds to the therapeutical antacid activity. Data obtained with aluminum containing antacids are presented. PMID- 2185760 TI - Ofloxacin treatment of nongonococcal urethritis. A multi-center study in Asia. AB - Ofloxacin, a new quinolone antibacterial agent, is active in vitro against gonococcal and nongonococcal urogenital pathogens. Chlamydia trachomatis infection is the most common cause of nongonococcal urethritis. In a multicenter study in seven Asian countries, 105 mal patients with chlamydial urethritis and 46 male patients with nongonococcal and nonchlamydial urethritis were treated with oral ofloxacin at a dosage of 200 mg twice daily for 5 to 10 days. The evaluation performed at day 5 and/or day 10 after treatment revealed good results in 58.2% and 96.8% of the chlamydial urethritis group, and 73.1% and 79.4% of the nongonococcal, nonchlamydial urethritis group, respectively. No severe side effects were observed. Ten-day treatment with ofloxacin showed good clinical efficacy on nongonococcal urethritis. PMID- 2185761 TI - Recent developments in atherogenesis. AB - This review attempts to highlight some new developments in the study of atherosclerosis with respect to lipoprotein and cellular elements of the aortic wall. The studies reviewed have shown that in addition to LDL (low density lipoprotein), atherogenic lipoproteins comprise also beta-VLDL (very low density lipoprotein), Lp (a) (lipoprotein (a)), peroxidatively modified LDL and remnant lipoproteins. The latter two were shown to interact preferentially with macrophages, the main cellular elements of fatty streaks. New information has also accrued with regard to improved identification of macrophage and smooth muscle derived foam cells and the presence of T-lymphocytes in the atheroma has been firmly established. The interaction of the various lipoproteins with the cellular elements and the role of lymphokines and growth factors in the formation of the atheroma are reviewed. PMID- 2185762 TI - [Interaction of cholesterol in plasma and cholesterol in the vessel wall]. AB - It has been known for a long time that cholesterol is an important constituent of degenerative lesions of the arterial wall. During the last 20 years epidemiological studies have shown that the risk for coronary heart disease is strongly correlated with the plasma levels of cholesterol and in particular with LDL (low density lipoprotein) cholesterol. The interactions between LDL and cells of the arterial wall have been investigated and recent findings suggest a model which explains the formation of early atherosclerotic lesions starting from increased LDL cholesterol concentrations. Further progression of lesions is characterised by continuous lipid accumulation with a relative increase of free cholesterol at the expense of cholesteryl esters. Regression even of advanced lesions can be achieved by vigorous lipid lowering therapy. The mechanisms of "reverse cholesterol transport" involved in this process are now understood to some extent. PMID- 2185763 TI - Determinants of the atherogenic flux of low-density lipoprotein into arteries. AB - Evidence is provided that in anaesthetized rabbits the atherogenic uptake of low density lipoprotein (LDL) by arterial walls is accelerated by norepinephrine at its physiological concentrations in rabbit and human blood. The principle of the experiments was to compare the uptake of intravenously injected, radioactively labelled LDL, methylated to prevent removal by high-affinity receptors, in the two carotid arteries of anaesthetized rabbits after infusing low concentrations of norepinephrine noradrenaline into one carotid and saline as control into the other, the volume rates of infusion being about 1% of the carotid blood flows. The results thus obtained may contribute towards an explanation for the accelerated atherosclerosis and the increased incidence of its clinical manifestation in conditions associated with elevated blood norepinephrine concentrations, including the episodic increases associated with stress and cigarette smoking as well as the more persistent increases caused by phaeochromocytoma. PMID- 2185765 TI - [Migration and proliferation of smooth muscle cells in the vessel wall]. AB - 1. Intimal migration and proliferation causing artery stenoses in the course of atherogenesis can be inhibited by various drugs. 2. Secondary stenoses after ballooning of arteries are caused mainly by proliferation of smooth muscle cells. 3. Ballooning of arteries or repeated transmural electrical stimulations of artery walls with weak electrical current is followed by an increased mitotic activity of smooth muscle cells in the ballooned resp. stimulated area which reaches a maximal value about one week following the onset of the experiment. The mitotic activity returns then slowly to initial levels. 4. Adaptations to proliferation-inducing stimuli are possible. The experiments demonstrate that the proliferative phases in atherogenesis can be explained as a sequence of adaptations and deadaptations (= change of disposition) to the proliferation inducing stimuli. 5. To select qualified drugs for an inhibition of the development of intimal proliferates in the course of atherogenesis makes it necessary to combine in vivo tests in animal experiments with tests on cell cultures of human cells from artery walls. PMID- 2185764 TI - [The significance of rheologic mechanisms in atherogenesis]. AB - Beside the well-known risk factors for atherogenesis fibrinogen is an independent risk factor. High plasma fibrinogen levels predispose to hypercoagulability and thrombotic processes. Furthermore, rheological mechanisms, interfering with cell to-cell contacts, and fluid-dynamic factors, facilitate local endothelial lesions resulting in atherosclerosis. Plasma fibrinogen, as the major contributing factor to plasma viscosity and red-blood-cell aggregation can limit oxygen supply and blood flow in microcirculation even in the absence of apparent coronary artery disease. Pharmacological interventions, in order to decrease elevated fibrinogen levels, do improve myocardial ischemia in patients with severe coronary artery disease. PMID- 2185766 TI - [The effect of Ca++ antagonists on cellular lipid metabolism]. AB - The antiatherogenic effects of Ca2(+)-antagonists have been proved in animal studies and in man. It is suggested that drugs of this class--unlike lipid lowering drugs--do not exert their effects by decreasing lipoprotein plasma levels but by a modulation of signal transducers. Ca2(+)-antagonists inhibit the extracellular matrix synthesis and thereby decrease cell adhesion and the modification of matrix-bound low density lipoproteins (LDL). Thus less modified LDL are produced, which are catabolized by scavenging or by phagocytosis of macrophages, leading to a reduction of foam cell production. Ca2(+)-antagonists also enhance the synthesis of membrane phospholipids, e.g. sphingomyelin (SPM), thereby increasing the membrane turnover and fluidity. In addition they positively influence the formation and catabolism of radicals. The resulting membrane protective effects possibly delay the general ageing process and improve the integrity of the cytoskeleton as well as of the adjacent membranes. In various studies it has been established that the use of Ca2(+)-antagonists leads to a reversal of atherosclerotic processes at the stage of early lesions. The effects of this class of drugs on a molecular level will be a focal point of future research. Of special importance will be the study of the cell specific signal transducing processes in those types of cells involved in atherosclerosis and the understanding of their role in the process as a whole. PMID- 2185767 TI - [What is the position of atherogenesis in current clinical cardiology?]. AB - The Gottingen risk incidence and prevalence studies (GRIPS) are a good example of the fruitful cooperation between experts in lipidology and clinical cardiology. Integrated research by experts in epidemiology, lipidology, genetics, blood pressure regulation and clinical cardiologists is deemed necessary to cope with the multifactorial etiology of atherosclerosis. PMID- 2185768 TI - [What therapeutic measures ensure long-term effect in coronary heart disease?]. AB - This paper describes the long-term effect of conservative, interventional and surgical treatment in coronary heart disease on the prognosis and on the quality of life. It is difficult to decide if prognosis or quality of life is more influenced by the different therapeutic measures. PMID- 2185769 TI - [Which therapeutic measures ensure good long-term results in arterial occlusive disease?]. AB - The lumen-opening methods reconstructive operation, angioplasty and thrombolysis achieve their best long-term results in the region of the large iliofemoral arteries. After elimination of occlusions in arteries situated more peripherally, reobliterations are more frequent and not uncommonly associated with a deterioration in the course of the disease. Of the conservative measures, long term benefit is to be expected primarily from continuous training. Pharmacotherapy with anticoagulants or inhibitors of thrombocyte function (acetylsalicylic acid) is likely to be successful in certain patients. PMID- 2185770 TI - [In whom, when and how should increased cholesterol values be treated?]. AB - High cholesterol values enhance the development of coronary heart disease. Therefore they must be normalized within the framework of a primary and secondary prevention. Apart from the risk factor cholesterol, other influencable and non influencencable risk factors play a decisive role for the patient concerned. The simultaneous presence of these factors also finally determines the intensity of the lipid-lowering therapy. For a successful therapy, besides dietary measures, modern therapeutic drugs are available, and their use--as a rule--helps to normalize moderate and strongly increased cholesterol values. Despite all help in decision-making it always will remain the decision of a responsible doctor, which measures he will take to reduce the individual coronary risk of a particular patient entrusted to him. PMID- 2185771 TI - [Maximal treatment of hypercholesteremia: what is possible?]. AB - A therapeutic strategy is presented which combines the use of HMG-CoA (3-hydroxy 3-methylglutaryl-CoA) reductase inhibitors with extracorporeal HELP-apheresis for the simultaneous elimination of LDL and plasma fibrinogen to ideal plasma concentrations. With HELP-treatment alone LDL (low density lipoprotein) cholesterol and fibrinogen could be reduced to approx. 50-60% of original plasma levels; medication with HMG-CoA reductase inhibitors alone caused a LDL cholesterol decrease by a mean of 40% from the untreated values. A combination of both methods led to a reduction in the LDL-cholesterol values of 70-80%. The high efficacy and safety of this combined treatment in patients with coronary artery disease (CAD) offers the possibility to normalize even markedly severe heterozygous hypercholesterolemia with plasma-LDL concentrations of about 450 mg/dl to ideal LDL-levels of below 120 mg/dl. This therapeutic strategy may be useful in the secondary prevention of CAD in patients with and without familial hypercholesterolemia if plasma cholesterol cannot be reduced by diet and drug treatment to a sufficient extent. Presumably one to two years of treatment will be required to retard the CAD and could initiate a regression of coronary sclerosis. PMID- 2185772 TI - [Prevention of classical risk factors. A public health and health policy task]. AB - Epidemiologic cohort studies such as Framingham, Tecumseh, Evans County and the Multiple Risk Factor Intervention Trial Cohort Study have shown, that hypercholesterolemia, hypertension and cigarette smoking are the strongest predictors for cardiovascular diseases and especially for coronary heart disease. From the intervention studies of the last two decades it has been learn that reductions of the risk factors hypercholesterolemia and hypertension have led to the predicted reductions in cardiovascular and all cause mortality. Two strategies are available for the prevention of hypercholesterolemia and hypertension: The population strategy and the high risk strategy. With regard to cholesterol and blood pressure the population approach strives for the shifting of the respective population distributions to the left i.e. to lower values. The high risk strategy on the other hand restricts itself to the 10-20% of the population with very high values. A comparison of the population and high risk strategy shows, that only the population strategy is radical in that only this strategy is capable to eliminate the causes of the incidence of hypercholesterolemia and hypertension. The high risk strategy on the other hand is unable to influence the total distribution curve. Population strategy and high risk strategy should be seen as complementary. To further reduce mortality and morbidity from cardiovascular diseases in the Federal Republic of Germany the following public health programs and health policy strategies must be applied: a) Reinforcement of the National High Blood Pressure Education Program. b) Establishment of a National High Cholesterol Education Program. c) Nationwide Anti-smoking Campaigns and Programs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185773 TI - [The National Cholesterol Education Program]. AB - Following a recommendation by the US Consensus Conference of December 1984, a National Cholesterol Education Program was initiated by about 30 different organizations. This program mainly addresses health professionals, such as physicians, nurses, dietitians etc. One of its objectives is to give physicians clear guidelines as to type and timing of interventions (diet, drugs). The program further comprises an extensive advertising campaign with the aim of reducing risk factors mainly by popularizing health-oriented nutrition. PMID- 2185774 TI - Speechreading training: believe it or not! PMID- 2185775 TI - Demographic information from the membership update survey. PMID- 2185776 TI - PL 99-457: are speech-language pathologists prepared for the challenge? PMID- 2185777 TI - Increasing computer literacy in speech-language pathology students. PMID- 2185778 TI - Major issues affecting the delivery of services in hospital settings. Recommendations and strategies. AB - The critical issues addressed in this report will escalate and continue to have an impact on service delivery. Rapid response to these issues as they arise and evolve is more urgent now than ever. Decisions on health care services--the type, the amount, the provider, and the recipient--are increasingly being made by non practitioners seeking cost savings in a system moving out of control. Speech language pathologists and audiologists in hospital settings need timely information and support to deal with these critical areas and thereby ensure continued services to communicatively impaired persons well into the 21st century. PMID- 2185779 TI - Status report on the NBME's computer-based testing. PMID- 2185780 TI - The costimulatory function of antigen-presenting cells. AB - In addition to the expression of MHC-antigen complexes and molecules which non specifically promote cell adhesion, antigen-presenting cells (APCs) provide costimulatory activity for T-lymphocyte stimulation. Costimulatory molecules are essential for activation and multiplication: the presentation of antigen by cells lacking such molecules may lead to T-cell tolerance. In this review, Casey Weaver and Emil Unanue update information on interleukin 1 (IL-1), the original and best studied costimulator, and investigate the nature of novel, as yet uncharacterized, costimulatory molecules. PMID- 2185781 TI - Antiphospholipid antibodies: more than just a disease marker? AB - Considerable interest has arisen over the past few years in a clinical syndrome characterized by a tendency to arterial or venous thrombosis, and the presence in the serum of antibodies to anionic phospholipids. In this article, Charles Mackworth-Young reviews the clinical features of this so-called 'anti phospholipid syndrome', the characteristics of the anti-phospholipid response and the evidence for a possible role for these antibodies in pathogenesis. PMID- 2185782 TI - Vaccination against Brucella. AB - Vaccination has played an enormous role in reducing brucellosis in many countries. It is certain to continue to be the preeminent factor in control of the disease in others. The search for an ideal vaccine continues. Live vaccines have proved to be superior to inactivated products. They are effective, inexpensive, and immunity is more persistent. The disadvantages of postvaccinal antibodies can be minimized by reduction of previously recommended doses and through use of supplemental diagnostic tests. These procedures now make entire population vaccination of great practical significance with many advantages over limited use of the strains 19 and Rev. 1. Adult animal vaccination should be much more extensive in many countries. A live B. suis strain 2 vaccine developed in China deserves much additional evaluation, including use in swine, for which no satisfactory vaccine exists. It is generally agreed that cell-mediated responses are the dominant aspect of immunogenesis. However, the correlates that have frequently been used--dermal hypersensitivity and lymphocyte stimulation in vitro -appear to be poor indices of cell-mediated immunity in brucellosis. Many studies have shown that postvaccinal antibodies do not predict subsequent immunity. There is a great need for simple in vivo or in vitro methods to measure CMI. While vaccination of humans may be useful in control of brucellosis in some high-risk occupations, the ultimate success is dependent upon reduction of this very important zoonosis in natural hosts. This is most effectively accomplished by widespread use of vaccination. PMID- 2185783 TI - Pertussis vaccines: present status. AB - The eradication of pertussis as a worldwide disease is unforeseeable for the present and immediate future. Mortality and morbidity from clinical pertussis are still commonly reported, especially in underdeveloped countries where mass immunization programs are virtually nonexistent. To achieve control of the disease, a high level of immunization coverage is necessary, and pertussis WCPV still remains one of the most effective bacterial vaccines. But, primarily because of its reactogenicity for infants, much effort has been directed toward the characterization of bacterial components important in pathogenesis and for the development of acellular vaccines. Progress in the last decade has resulted in the production and use of such vaccines for routine vaccination, and their use in Japan, as well as the recent clinical trials in Sweden and several phase I/II studies in other countries, has shown that these preparations are safer than conventional WCPV, and equally effective, in preventing disease. The development of future acellular pertussis vaccines by gene manipulation may finally inspire public confidence for vaccine prophylaxis, eventually leading to eradication of the disease. However, the production and use of such sophisticated vaccines is dependent on many factors, and consequently conventional WCPV may still be used in many countries for several years to come. PMID- 2185784 TI - Vaccines against leprosy. PMID- 2185785 TI - Liposomes as carrier and immunoadjuvant of vaccine antigens. PMID- 2185786 TI - Surface chemistry and classification of vaccine adjuvants and vehicles. PMID- 2185787 TI - Tetanus vaccine: present status. PMID- 2185788 TI - Klebsiella polysaccharide vaccines. PMID- 2185789 TI - Paraganglioma of the cauda equina: a case report and review of the literature. AB - A rare slowly growing paraganglioma of the cauda equina is described, with characteristic immunocytochemical and electron microscopic appearances. Twenty one cases of similar tumours have been reported at this site. The literature is reviewed and the main features discussed. PMID- 2185790 TI - Schwannoma of the oculomotor nerve. AB - A case is described of oculomotor nerve sheath tumour presenting with signs and symptoms of a posterior fossa space occupying lesion with minimal involvement of the IIIrd nerve. PMID- 2185791 TI - A double blind placebo controlled trial of the calcium entry blocking drug, nicardipine, in the treatment of vasospasm following severe head injury. AB - A double blind, placebo controlled trial of nicardipine in the treatment of high Doppler Flow Velocity (DFV) following severe head injury (Glasgow Coma Score (GSC) less than or equal to 8) was performed. Thirty patients with high DFV (greater than or equal to 100 cm/s for 6 h duration) on transcranial Doppler ultrasound, were treated with nicardipine or placebo for 24 h (2.5 mg/h, increasing in steps of 2.5 mg/h at 2 h intervals (maximum rate 7.5 mg/h) depending on response of DFV). DFV was measured hourly for 24 h and then every 12 h for 2 days. Nicardipine significantly reduced DFV below the threshold of 100 cm/s (16/19 cf placebo 3/11, chi-square p less than 0.001). In the nicardipine treated group maximum DFV was significantly reduced (p less than 0.001) and time with DFV below 100 was significantly longer. Rises in DFV were significantly reduced by the drug if the DFV was normal at the time of entry. High DFV returned on cessation of the infusion. No unexpected or adverse side effects were seen. No clinical benefit was demonstrable. PMID- 2185792 TI - Lymphokine-activated killer cell expansion for clinical trials of adoptive immunotherapy with interleukin-2: optimization of the culture technique. AB - On leukopheresis products obtained from patients included in a protocol interleukin-2/lymphokine-activated killer (IL-2/LAK) cell therapy, we analyzed, in parallel with the standard culture and on large volumes of these products, different parameters which could either improve LAK cell enhancement or simplify the procedure. We demonstrated first that purification of the mononuclear cells from the leukopheresis product before its culture is not required. An excess of red blood cells and granulocytes (up to 50%) in nonpurified samples improved both the mononuclear cell recovery in short-term culture (4 days) and the activation of LAK cells when the total nuclear cell concentration did not exceed 3 X 10(6)/ml. Different factors can contribute to this enhancing effect: the presence of red blood cells, the liberation of cytokines by granulocytes, or the loss of a population of activated lymphocytes, with liberation of cytokines by granulocytes, or the loss of a population of activated lymphocytes, with larger size and density than resting lymphocytes, during the separation. Supplementation of the medium with 2% heat-inactivated autologous plasma obtained before any treatment rather than with 2% pooled human AB serum does not modify the mononuclear cell recovery in 4-day culture, but it does enhance LAK activity. The inhibitory effect of heat-inactivated autologous plasma on proliferation and activation of LAK cells was never observed, suggesting the absence of suppressive factors in the plasma of the 23 analyzed patients. Similarly, autologous plasma did not modify natural killer and LAK cell functions when added during the cytotoxic assay.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185793 TI - Characteristics of PHA-L4, the mitogenic isolectin of phytohemagglutinin, as an ideal biologic response modifier. AB - Phytohemagglutinin retains the properties of a theoretically ideal biologic response modifier in that it is available in a purely mitogenic L4 isolectin form that is stable; previously studied extensively; applicable as a simple skin test to assess immune competence and guide therapy; broadly immunostimulating with respect to both activation and proliferation of effector cell pathways; amenable to targeting maneuvers; stimulative of endogenous cytokine production; conveniently administrable by multiple routes; applicable to both active and adoptive immunotherapies; rapidly interacting irreversibly with lymphocytes; readily applied as a vaccine adjuvant; apparently nonsensitizing; relatively nontoxic, with maximum effective levels well below those for major toxicity; free from stress induction; nononcogenic; noninfectious; related to other mitogenic lectins that have augmenting therapeutic potential; compatible with other therapeutic modalities and conductive to collaborative use of other BRMs; well suited to application as a surgical adjuvant and for prophylaxis against malignancies or infections in susceptible individuals; applicative to debilitated, immunosuppressed, and myelosuppressed patients; probably compatible with pregnancy; and potentially cost-effective. PMID- 2185794 TI - Immunologic and toxicologic study of disaccharide tripeptide glycerol dipalmitoyl: a new lipophilic immunomodulator. AB - A new lipophilic immunomodulator, disaccharide tripeptide glycerol dipalmitoyl (DTP-GDP), has been synthesized and evaluated for its immunologic activity and toxicology. DTP-GDP alone or in liposomes is more effective as an adjuvant and in activating macrophages compared with muramyldipeptide (MDP). Preclinical studies demonstrate no evidence of toxicity, including vasculitis. DTP-GDP in liposomes has shown antitumor activity in phase I clinical trials. PMID- 2185795 TI - Metastatic cardiac liposarcoma: diagnosis by transesophageal echocardiography and magnetic resonance imaging. AB - The most superior portion of the right atrium is not well visualized by transthoracic echocardiography. This limits the ability of the technique to detect intracardiac disease in this area. We describe a 41-year-old man with a history of liposarcoma in whom transthoracic echocardiography was unable to elucidate a right atrial metastasis. Transesophageal echocardiography demonstrated the morphology and extent of the large right atrial mass. These findings were well correlated with both magnetic resonance imaging and surgery. PMID- 2185796 TI - Reimbursement update: looking toward the 1990s. AB - Some Medicare carriers have independently decided to treat all billings for echocardiographic services as radiologic, whereas others have decided to treat billings from multispecialty practices that include a radiologist as radiologic services. The result is that the radiology fee schedules are being applied, even though the services were not supplied by radiologists. PMID- 2185797 TI - Lower extremity venous imaging for the echocardiologist. AB - Cardiologists who are familiar with the techniques and the performance of echocardiography can easily learn how to study the lower extremity veins in their patients by using ultrasound imaging combined with pulsed-wave Doppler echocardiography (duplex scanning). In particular, duplex scanning is useful for diagnosing deep or superficial venous thrombosis, for assessing venous incompetence, and for mapping the superficial veins before surgical harvesting for bypass operations. Because questions about the veins arise frequently in the treatment of cardiovascular patients, the cardiologist who is knowledgeable about veins and venous disease can play a central role in the diagnostic workup and treatment of these patients. PMID- 2185798 TI - Myocardial perfusion studies by contrast echocardiography. AB - Determination of regional myocardial blood flow may provide clinically valuable information about ischemia, risk area, and the effect of angioplastic, surgical, and pharmacologic interventions. Contrast echocardiography, with use of prepared microbubbles of 4 to 8 microns size, graphically demonstrates perfusion characteristics in the catheterization laboratory. Analysis and interpretation of this data and the creation of contrast materials that will demonstrate myocardial perfusion after intravenous injection are some of the next challenges in these techniques. PMID- 2185799 TI - Intraoperative assessment of nodal staging at thoracotomy for carcinoma of the bronchus. AB - In the staging of operable carcinoma of the bronchus, accurate assessment of mediastinal nodal status is essential in order to determine the feasibility and desirability of resection. In the UK, frozen section analysis is often logistically difficult, and many surgeons rely upon naked-eye assessment. To evaluate the accuracy of this approach, we have reviewed 100 thoracotomies performed for cancer in this unit and compared the naked-eye assessment of nodal staging with the ultimate histological findings. A total of 287 lymph nodes were examined. There were 14 false positives and 10 false negatives. The overall accuracy of naked-eye assessment was 96.1%. On no occasion did an error in naked eye assessment result in a patient receiving inappropriate treatment. All patients were thought to be pTNM N0 or N1 prior to surgery, yet N2 disease was established in 24 patients. The value of routine mediastinal node dissection at the time of thoracotomy has been established and an important subgroup of patients with microscopic N2 disease has been identified. PMID- 2185800 TI - Improved mitral valve replacement. AB - We describe a simple, reproducible technique of achieving more normal left ventricular function after mitral valve replacement. Polytetrafluoroethylene (PTFE) sutures are used as chordae tendineae to restore the integrity between the mechanical valve and papillary muscles and thus the left ventricular wall. PMID- 2185801 TI - Transesophageal sonography in central bronchial carcinoma. AB - A new application of transesophageal sonography was tested in eight patients suffering from central bronchial carcinoma. Due to ultrasound technology, a real time investigation is feasible which enhances the diagnostic method of computed tomography (CT) by discriminating between tumour and mediastinal organs which cannot be delineated by CT only. Different sonographic densities and the movement between organ and tumour contribute to the diagnostic accuracy of sonography if operability is questionable due to possible organ infiltration by tumour. The method is limited by the air filled organs (trachea, bronchi), as ultrasound does not penetrate adequately. PMID- 2185802 TI - Pulmonary toxicity of cytotoxic and immunosuppressive agents. A review. AB - Cytotoxic agents may cause interstitial or eosinophilic pneumonitis, alveolar proteinosis, pulmonary venous occlusive disease, pulmonary fibrosis, pneumothorax, or pulmonary oedema. These agents may also potentiate lung injury caused by radiotherapy or high oxygen fractions in inspired air. Clinical and roentgenological features of lung damage induced by cytotoxic drugs are usually non-specific, and differential diagnoses include progression of the malignant disease and a plethora of opportunistic infections. Monitoring of blood gases and carbon monoxide transfer factor may facilitate early detection of drug induced lung injury. Fiberoptic bronchoscopy, bronchoalveolar lavage, transbronchial biopsy, or open lung biopsy may be necessary for reliable diagnosis. Early detection of lung damage and immediate withdrawal of the responsible agent(s) are essential. Steroids may be of therapeutic value in some patients. PMID- 2185803 TI - Recombinant leukocyte interferon alpha-2a and medroxyprogesterone in advanced renal cell carcinoma. A randomized trial. AB - In a randomized study of advanced renal cell carcinoma 60 patients were allocated to treatment with either recombinant interferon alpha-2a or medroxyprogesterone acetate. Correlation between the dose of interferon alpha-2a and plasma concentration indicated linear kinetics. Survival was similar in the two treatment groups. Only one complete and one partial response were seen in the interferon group and only one complete response in the medroxyprogesterone group, indicating a low therapeutic potential of both interferon and medroxyprogesterone. Interferon influenced the serum liver enzyme levels; increased transaminases were seen in 17 patients treated with interferon but in only four patients in the medroxyprogesterone group. Two patients had very high serum liver-enzyme levels concomitant with intolerable tiredness, in both patients the symptoms disappeared and the enzymes normalized after discontinuation of the interferon treatment. Antibodies to interferon developed frequently in patients receiving high dose oligomeric interferon therapy but rarely in patients receiving low dose monomeric interferon treatment. PMID- 2185804 TI - Results of treatment in locally advanced carcinoma of the endometrium. AB - The impact of treatment on survival was analyzed in 106 patients with carcinoma of the endometrium stage II (n = 61) and stage III (n = 45). There was no significant difference in survival in patients with stage II who were treated with radiation therapy alone or with combination of surgery and radiation therapy. Their five-year actuarial survival was 74.5% and 71.3% respectively (p = greater than 0.05). However, combined treatment was associated with significantly superior survival in patients with stage III disease where the survival was 57.3% versus 17.5% in patients who received irradiation alone (p = 0.01). Diagnosis of stage III disease based upon clinical (CS III) or pathological (PS III) findings was responsible for this difference in survival. Patients with CS III whose tumor could not be resected because of its extent carried poorer prognosis. Patients with stage II had excellent tumor control in pelvis as compared to patients with stage III. Treatment-related complications were minimal. Overall survival of patients with stage III was poor (33.8%) due to a high rate of pelvic and/or extrapelvic recurrences. PMID- 2185805 TI - Choroid plexus carcinoma--report of a case with metastases within the central nervous system. PMID- 2185806 TI - [Spontaneous biliodigestive fistula]. AB - A retrospective study was made of 23 cases of spontaneous biliodigestive fistulae collected from bile tract surgery performed in our center from 1979 to 1987, representing 1.05% of the total number of cases. The etiology was cholelithiasis in almost all cases and the most frequent connection was to the duodenum. Forty eight percent of the cases presented as biliary ileus. In each case surgery depended on the etiology, clinical manifestations and status of the patient. The mortality was 8.7% and the morbidity 52%. Results are analyzed and a bibliographic review of the topic is offered. PMID- 2185807 TI - [Pro-oxidation and anti-oxidation in gastroenterology. Importance of free radicals]. PMID- 2185808 TI - [Intravesical hematoma as a manifestation of hemobilia. Ultrasonic study]. PMID- 2185809 TI - Delusional halitosis. Review of the literature and analysis of 32 cases. AB - Halitosis, or bad breath, is a feature of some oral and systemic diseases. However, there are apparently healthy individuals who complain of having bad breath which no one else can smell and for which no local or systemic condition can be found. This condition, referred to in this article as delusional halitosis, has identical features with a psychiatric disorder, monosymptomatic hypochondriacal psychosis. This paper reviews the literature on halitosis and oral psychogenic disorders and presents an analysis of 32 cases of delusional halitosis that presented at the University of Benin Dental Hospital, Nigeria, in the period 1984-1986. PMID- 2185810 TI - The capitation study. 3. The views of participating dentists and the profession. AB - During the course of a 3-year parallel, controlled clinical trial comparing a capitation system of remuneration with fee-for-service for the dental care of children, the views of the dentists were gained through meetings, informal communication, and a structured questionnaire sent to every dentist in the study. The questionnaires completed by the dentists who had been in the study from the beginning were used in the analysis. The views of practice principals on practice administration were also gained. Dentists in capitation claimed to have greater clinical freedom than those in fee-for-service, but the system under test involved more practice administration. The trial allowed the two systems to be compared under limited, controlled conditions, thus benefiting any substantive scheme that might be developed from it. PMID- 2185811 TI - Alteration of humoral responses to Candida in HIV infection. AB - The objectives of this preliminary study were to determine the prevalence of oral candidal carriage and infection in a group of HIV-positive individuals and compare the humoral immune responses in serum and saliva in this group with a control group of HIV-negative subjects. Patients were examined clinically with particular reference to the presence of candidal lesions and oral swabs taken to identify carriers. Venous blood and whole saliva were obtained for estimation of total and anti-Candida antibody levels. Pseudomembranous candidiasis was the commonest clinical variant in HIV-positive individuals. Candida albicans was the commonest species isolated in both groups. Increased levels of anti-Candida IgG were found in both serum and saliva of HIV-negative individuals who were either carriers of Candida species or had clinical candidiasis. This was associated with a reciprocal fall in anti-Candida IgA. Similar trends were seen in HIV-positive individuals in association with candidal carriage and infection, although the changes were more marked. PMID- 2185812 TI - Contributions of William Hunter (1718-1783) to dental science. AB - This article briefly describes some of the many and varied contributions which William Hunter made to medical and dental science in the eighteenth century. His work provided the foundations from which anatomy became one of the cornerstones of modern medicine. Hunter's teaching methods are still influential today and his specimen collection is one of the most comprehensive in existence. PMID- 2185813 TI - Why are children starved? PMID- 2185814 TI - Paediatric glucose homeostasis during anaesthesia. AB - The perioperative blood glucose regulatory response was compared in 20 healthy children (aged 1-5 yr) presenting for minor surgery and allocated randomly to either a fasted or a glucose group. All children received a milk feed at midnight. The fasted group received no oral intake thereafter, whereas the glucose group received 5% dextrose water 10 ml kg-1 orally about 4 h before operation. The mean plasma glucose concentrations in the two groups were similar before operation and were within normal limits. The pattern of change in the concentrations of plasma glucose, insulin, cortisol, growth hormone and glucagon were also similar between the two groups. Ten percent of patients in the fasted group and 33% in the glucose group had gastric aspirates in excess of 0.4 ml kg 1. The pH of all gastric samples was less than 2.5. The results suggest that healthy preschool children were able to maintain glucose homeostasis after 8 h of fasting. Feeding within 4-6 h before surgery may increase the risk of pulmonary aspiration. PMID- 2185815 TI - Predictive value of FRC and respiratory compliance on pulmonary gas exchange induced by high frequency jet ventilation in humans. AB - To determine if functional residual capacity (FRC), compliance of the respiratory system (C), or underlying pulmonary disease are predictive for the efficacy of high frequency jet ventilation (HFJV) on pulmonary gas exchange, we investigated six adult patients within 4 h of abdominal surgery and six patients with severe adult respiratory distress syndrome. Gas exchange during intermittent positive pressure ventilation (IPPV) was compared with that during HFJV at frequencies of 100 b.p.m. (HFJV100) and 200 b.p.m. (HFJV200), resulting in a minute ventilation of about 400 ml kg-1 with both ventilatory frequencies, and in both groups of patients. Baseline FRC and C were measured during IPPV with the multiple-breath nitrogen washout method and from expiratory pressure-volume curves, respectively. Changes in the alveolar-arterial oxygen difference (PAO2 - PaO2): FIO2 ratio induced by HFJV correlated negatively with C (HFJV100: r = -0.78, P less than 0.005; HFJV200: r = -0.84, P less than 0.005); that is, greater oxygenation was obtained in patients with a better compliance. Similarly, changes in arterial partial pressure of carbon dioxide (PaCO2) induced by HFJV correlated negatively with C (HFJV100: r = -0.77, P less than 0.001; HFJV200: r = -0.61, P less than 0.05). In contrast, there was no significant correlation between FRC measured during IPPV and changes in (PAO2 - PaO2): FIO2 ratio or PaCO2 induced by HFJV, as these changes were influenced more by the patient's pulmonary disease than by baseline FRC. These results should be interpreted in the context of different underlying pathophysiological mechanisms reducing FRC in both groups of patients. PMID- 2185816 TI - Gas exchange during anaesthesia. PMID- 2185817 TI - In vitro priming of human bone marrow with recombinant GM-CSF. PMID- 2185818 TI - Hysteroscopic alternatives to hysterectomy. PMID- 2185819 TI - Cytological terminology. PMID- 2185820 TI - Early pregnancy tests. PMID- 2185821 TI - Pregnancy and exercise--exercise and pregnancy. A short review. PMID- 2185822 TI - The use of mifepristone (RU 486) for cervical preparation in first trimester pregnancy termination by vacuum aspiration. World Health Organization. Task Force on Post-ovulatory Methods for Fertility Regulation. AB - Animal and clinical evidence suggests that the antiprogestin mifepristone may be of potential use for cervical preparation before surgical termination of pregnancy. A double-blind, multicentre study was undertaken of 230 primigravid women with 10-12 weeks amenorrhoea who were randomly assigned to groups given 0 (placebo), 25, 50 or 100 mg mifepristone twice at 24 and 12 h before vacuum aspiration. In mifepristone-treated women the cervix was on average between 0.9 and 1.2 mm more dilated at operation, but the effect was not dose related. High resistance during further mechanical stretching tended to be encountered more often and at a smaller cervical diameter in the placebo group than in the women given mifepristone, but these differences were not statistically significant. In contrast, the ease of dilatation assessed subjectively by the operating surgeons was not only improved by the antiprogestin, but was also dose related. Mifepristone therapy was not associated with any side-effects and only two of the women from the highest dose group experienced preoperative vaginal bleeding. Peroperative blood loss, post-operative complications, the duration of post operative bleeding and the interval to the first period were similar in the four treatment groups. PMID- 2185823 TI - Pregnancy screening by Doppler uteroplacental and umbilical artery waveforms. PMID- 2185824 TI - The effect of patterns of rumen fermentation on the response by dairy cows to dietary protein concentration. AB - Four groups of seven dairy cows were given hay plus high-fibre concentrates based on sugar-beet feed (hay-concentrate, 40:60 w/w) or high-starch concentrates based on flaked maize (hay-concentrate, 20:80 w/w), with a crude protein (nitrogen x 6.25) content of either 160 or 220 g/kg dry matter, over weeks 4-18 of lactation. Performance during week 3 of lactation, when all cows were fed on a standard ration, was used as a covariate. For diets with a high-fibre content, higher protein concentrations led to increases in yields of milk and milk fat, with no effect on live-weight loss. For diets with a high-starch content, higher protein concentrations did not affect milk yield or composition but resulted in an increase in live weight rather than a decrease. Diets with a high-starch content led to increased proportions of propionic acid in the rumen and increased concentrations of insulin in the blood. It is concluded that the source of carbohydrate needs to be taken into account when predicting the response to protein supply by dairy cows. PMID- 2185825 TI - Alpha-amylase (EC 3.2.1.1) susceptibility rather than viscosity or gastric emptying rate controls plasma responses to starch in healthy humans. AB - The relationship between starch alpha-amylase (EC 3.2.1.1) susceptibility, plasma responses and gastric emptying rates has been investigated in humans. Nine randomly chosen healthy subjects were given three carbohydrate test meals (25 g starch or equivalent glucose units): two maize starch pastes with (a) 240 (S24) or (b) 500 (S50) g amylose/kg, and a glucose solution (GS). At 30 min, in vitro starch alpha-amylolysis was 48 (SD 4)% for S24 and 35 (SD 4)% for S50. Test meals differed in viscosity (mPa x s: S24, 54,000; S50, 190; GS, 4). Carbohydrates were labelled with 99mTechnetium and isotope gastric emptying was measured by external gamma counting. Carbohydrate isotopic gastric emptying patterns were exponential. Half gastric emptying time (min) was significantly (P less than 0.05) shorter for S50 (19(SD 2] than for GS (26(SD 2] or S24 (29(SD 2]. No correlation was found between half gastric emptying time and plasma response values. Values for peak insulin (pmol/l) above fasting were significantly (P less than 0.05) different: GS, 306 (SD 11); S24, 227 (SD 11); S50, 187 (SD 11). It is concluded that alpha amylase susceptibility of the test carbohydrates is a determining factor in the insulin response of healthy subjects, while viscosity of the test meals and gastric emptying rate have no effect. PMID- 2185826 TI - Paradoxical effects of essential fatty acid supplementation on lipid profiles and sweat electrolytes in cystic fibrosis. AB - Supplements of evening primrose oil (Oenothera biennis), which contains at least 72% linoleic (18:2n-6) and 7% gamma-linolenic (18:3 n-6) acids (expressed as % fatty acid methyl esters) were given to sixteen cystic fibrosis patients for a period of 12 months. Clinical observations showed no significant changes in patients' weights or respiratory function throughout. Linoleic acid levels in plasma and erythrocyte membranes increased significantly during the first 6 months but this increase was not sustained at its initial level. After supplementation was discontinued reversion to baseline (low) levels occurred within 4 months. Levels of plasma prostaglandins (PG) and urinary PG metabolites varied among individuals over a wide range, and urinary PGF2 alpha metabolites fell during the supplementation. There was a significant fall in sweat sodium concentrations after 6 weeks of supplementation, but sweat chloride was unchanged. It is not known whether the effect of essential fatty acids on sweat Na+ reflects changes in cell membrane conformation or if there is a direct effect on Na+ pump activity. PMID- 2185827 TI - Localization of alpha 1----3-linked mannoses in the N-linked oligosaccharides of Saccharomyces cerevisiae mnn mutants. AB - Neutral and phosphorylated N-linked oligosaccharides were isolated from Saccharomyces cerevisiae mnn9 and mnn9 gls1 mutant mannoproteins and separated into homologues that differed in the number of terminal alpha 1----3-linked mannoses. In each type of oligosaccharide, the addition of such mannose was shown to occur in an ordered rather than a random fashion. The results confirm and extend an earlier report that dealt with the N-linked oligosaccharides from yeast invertase [Trimble, R.B., & Atkinson, P.H. (1986) J. Biol. Chem. 261, 9815-9824], and they suggest that the postulated processing pathway can be generalized to include phosphorylated and glucose-containing N-linked oligomannosides. We conclude that this processing pathway is identical for the analogous oligosaccharides from the mnn9 and wild-type strains of S. cerevisiae. Analysis of the mnn2 mnn10 mannoprotein revealed that a similar modification occurred at the branched terminus of the outer chain as well as in the core in this mutant. PMID- 2185828 TI - Effect of oligosaccharides and chloride on the oligomeric structures of external, internal, and deglycosylated invertase. AB - External invertase exists in an oligomeric equilibrium of dimer, tetramer, hexamer, and octamer, the concentrations of which vary with pH, time, and concentration of enzyme [Chu, F.K., Watorek, W., & Maley, F. (1983) Arch. Biochem. Biophys. 223, 543-555; Tammi, M., Ballou, L., Taylor, A., & Ballou, C.E. (1987) J. Biol. Chem. 262, 4395-4401]. To assess the influence of carbohydrate on this equilibrium, we investigated the self-association of external invertase (10 oligosaccharides per subunit), deglycosylated external invertase (2 oligosaccharides per subunit), and internal invertase (no carbohydrate) under various conditions. In addition, the effect of carbohydrate on the interaction of the subunits of these various invertases to form heterooligomers was studied. Chloride ion was found to promote subunit association in the various invertases irrespective of their glycosylation status. However, external invertase was less responsive to chloride ion relative to the internal and deglycosylated invertases. The higher oligomers of deglycosylated invertase were stable at 47 degrees C whereas those of external invertase dissociated rapidly into dimers, suggesting that the additional oligosaccharides in external invertase destabilize subunit interaction. Hybridization experiments with the various invertases showed that the dimers of internal invertase formed heterooligomers with either external or deglycosylated invertase. By contrast, the monomers of external and internal invertases formed their respective homodimers, but not heterodimers. These results suggest that the oligosaccharide content of invertase not only influences the extent of self-association but also affects heterooligomer formation. PMID- 2185829 TI - A sensitive genetic assay for the detection of cytosine deamination: determination of rate constants and the activation energy. AB - Previously it has not been possible to determine the rate of deamination of cytosine in DNA at 37 degrees C because this reaction occurs so slowly. We describe here a sensitive genetic assay to measure the rate of cytosine deamination in DNA at a single cytosine residue. The assay is based on reversion of a mutant in the lacZ alpha gene coding sequence of bacteriophage M13mp2 and employs ung- bacterial strains lacking the enzyme uracil glycosylase. The assay is sufficiently sensitive to allow us to detect, at a given site, a single deamination event occurring with a background frequency as low as 1 in 200,000. With this assay, we determined cytosine deamination rate constants in single stranded DNA at temperatures ranging from 30 to 90 degrees C and then calculated that the activation energy for cytosine deamination in single-stranded DNA is 28 +/- 1 kcal/mol. At 80 degrees C, deamination rate constants at six sites varied by less than a factor of 3. At 37 degrees C, the cytosine deamination rate constants for single- and double-stranded DNA at pH 7.4 are 1 x 10(-10) and about 7 x 10(-13) per second, respectively. (In other words, the measured half-life for cytosine in single-stranded DNA at 37 degrees C is ca. 200 years, while in double stranded DNA it is on the order of 30,000 years.) Thus, cytosine is deaminated approximately 140-fold more slowly when present in the double helix. These and other data indicate that the rate of deamination is strongly dependent upon DNA structure and the degree of protonation of the cytosine. The data suggest that agents which perturb DNA structure or facilitate direct protonation of cytosine may induce deamination at biologically significant rates. The assay provides a means to directly test the hypothesis. PMID- 2185830 TI - Differential scanning calorimetry of the unfolding of myosin subfragment 1, subfragment 2, and heavy meromyosin. AB - The thermal unfolding of rabbit skeletal heavy meromyosin (HMM), myosin subfragment 1, and subfragment 2 has been studied by differential scanning calorimetry (DSC). Two distinct endotherms are observed in the DSC scan of heavy meromyosin. The first endotherm, with a Tm of 41 degrees C at pH 7.9 in 0.1 M KCl, is assigned to the unfolding of the subfragment 2 domain of HMM based on scans of isolated subfragment 2. The unfolding of the subfragment 2 domain is reversible both in the isolated form and in HMM. The unfolding of subfragment 2 in HMM can be fit as a single two-state transition with a delta Hvh and delta Hcal of 161 kcal/mol, indicating that subfragment 2 exists as a single domain in HMM. The unfolding of subfragment 2 is characterized by an extraordinarily large delta Cp of approximately 30,000 cal/(deg.mol). In the presence of nucleotides, the high-temperature HMM endotherm with a Tm of 48 degrees C shifts to higher temperature, indicating that this peak corresponds to the unfolding of the subfragment 1 domain. This assignment has been confirmed by comparison with isolated subfragment 1. The stabilizing effect of AMPPNP was significantly greater than that of ADP. The vanadate-trapped ADP species was slightly more stable than M.AMPPNP with a Tm at 58 degrees C. The unfolding of subfragment 1, both in the isolated form and in HMM, was irreversible. Only a single endotherm was noted in the DSC scans of the subfragment 1 domain of HMM and in freshly prepared subfragment 1 complexes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185831 TI - Isolation and functional reconstitution of soluble melibiose permease from Escherichia coli. AB - By use of techniques described recently for lac permease [Roepe, P.D., & Kaback, H.R. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 6087], the melibiose permease from Escherichia coli, another polytopic integral plasma membrane protein, has been purified in a metastable soluble form after overexpression of the melB gene via the T7 RNA polymerase system. As demonstrated with lac permease, soluble melibiose permease is dissociated from the membrane with 5.0 M urea and appears to remain soluble in phosphate buffer at neutral pH after removal of urea by dialysis, although the protein aggregates in a time- and concentration-dependent fashion. Moreover, soluble melibiose permease behaves as a monomer during purification by size exclusion chromatography in the presence of urea. Circular dichroism of purified soluble melibiose permease reveals that the protein is highly helical in potassium phosphate buffer and that secondary structure is disrupted in 5.0 M urea. Finally, purified melibiose permease can be reconstituted into proteoliposomes, and the preparations catalyze membrane potential driven H+/melibiose or Na+/methyl 1-thio-beta,D-galactopyranoside symport. The results provide further support for the notion that hydrophobic transmembrane proteins may be able to assume a nondenatured conformation in aqueous solution and extend the implication that the approach described may represent a general method for rapid isolation and reconstitution of this class of membrane proteins. PMID- 2185832 TI - Stabilization of a reaction intermediate as a catalytic device: definition of the functional role of the flexible loop in triosephosphate isomerase. AB - The function of the mobile loop of triosephosphate isomerase has been investigated by deleting four contiguous residues from the part of this loop that interacts directly with the bound substrate. From the crystal structure of the wild-type enzyme, it appears that this excision will not significantly alter the conformation of the rest of the main chain of the protein. The specific catalytic activity of the purified mutant enzyme is nearly 10(5)-fold lower than that of the wild type. Kinetic measurements and isotopic partitioning studies show that the decrease in activity is due to much higher activation barriers for the enolization of enzyme-bound substrate. Although the substrates bind somewhat more weakly to the mutant enzyme than to the wild type, the intermediate analogue phosphoglycolohydroxamate binds much less well (by 200-fold) to the mutant. It seems that the deleted residues of the loop contribute critically to the stabilization of the enediol phosphate intermediate. Consistent with this view, the mutant enzyme can no longer prevent the loss of the enediol phosphate from the active site and its rapid decomposition to methylglyoxal and inorganic phosphate. Indeed, when glyceraldehyde 3-phosphate is the substrate, the enediol phosphate intermediate is lost (and decomposes) 5.5 times faster than it reprotonates to form the product dihydroxyacetone phosphate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185833 TI - Characterization by electron microscopy of isolated particles and two-dimensional crystals of the CP47-D1-D2-cytochrome b-559 complex of photosystem II. AB - A photosystem II complex containing the reaction center proteins D1 and D2, a 47 kDa chlorophyll-binding protein (CP47), and cytochrome b-559 was isolated with high yield, purity, and homogeneity; small but well-ordered two-dimensional crystals were prepared from the particles. The crystals and the isolated particles were analyzed by electron microscopy using negatively stained specimens. The information of 20 different digitized crystals was combined by alignment programs based on correlation methods to obtain a final average. The calculated diffraction pattern, with spots up to a resolution of 2.5 nm, and the optical diffraction pattern of a single crystal indicate that the plane group is p22121 (also called p2gg) and that the unit cell is rectangular with parameters of 23.5 x 16.0 nm, containing four stain-excluding monomers (two face-up and two face-down). In projection, the monomers have an asymmetrical shape with a length of 10 nm, a maximal width of 7.5 nm, and a height of 6 nm; their molecular mass is 175 +/- 40 kDa. PMID- 2185834 TI - Site-specific incorporation of 5-fluorotryptophan as a probe of the structure and function of the membrane-bound D-lactate dehydrogenase of Escherichia coli: a 19F nuclear magnetic resonance study. AB - The structure and function of the membrane-bound D-lactate dehydrogenase of Escherichia coli have been investigated by fluorine-19 nuclear magnetic resonance spectroscopy of 5-fluorotryptophan-labeled enzyme in conjunction with oligonucleotide-directed, site-specific mutagenesis. 5-Fluorotryptophan has been substituted for nine phenylalanine, tyrosine, and leucine residues in the enzyme molecule without loss of activity. The 19F signals from these additional tryptophan residues have been used as markers for sensitivity to substrate, exposure to aqueous solvent, and proximity to a lipid-bound spin-label. The nuclear magnetic resonance data show that two mutational sites, at amino acid residues 340 and 361, are near the lipid environment used to stabilize the enzyme. There are a number of amino acid residues on the carboxyl side of this region that are strongly sensitive to the aqueous solvent. The environment of the wild-type tryptophan residue at position 469 changes as a result of two of the substitution mutations, suggesting some amino acid residue-residue interactions. Secondary structure prediction methods indicate a possible binding site for the flavin adenine dinucleotide cofactor in the carboxyl end of the enzyme molecule. These results suggest that the membrane-bound D-lactate dehydrogenase may have the two-domain structure of many cytoplasmic dehydrogenases but with the addition of a membrane-binding domain between the catalytic and cofactor-binding domains. This type of three-domain structure may be of general significance for understanding the structure of membrane-bound proteins which do not traverse the lipid bilayer of membranes. PMID- 2185835 TI - Crystal structures of Escherichia coli dihydrofolate reductase: the NADP+ holoenzyme and the folate.NADP+ ternary complex. Substrate binding and a model for the transition state. AB - The crystal structure of dihydrofolate reductase (EC 1.5.1.3) from Escherichia coli has been solved as the binary complex with NADP+ (the holoenzyme) and as the ternary complex with NADP+ and folate. The Bragg law resolutions of the structures are 2.4 and 2.5 A, respectively. The new crystal forms are nonisomorphous with each other and with the methotrexate binary complex reported earlier [Bolin, J. T., Filman, D. J., Matthews, D. A., Hamlin, R. C., & Kraut, J. (1982) J. Biol. Chem. 257, 13650-13662]. In general, NADP+ and folate binding conform to predictions, but the nicotinamide moiety of NADP+ is disordered in the holoenzyme and ordered in the ternary complex. A mobile loop (residues 16-20) involved in binding the nicotinamide is also disordered in the holoenzyme. We report a detailed analysis of the binding interactions for both ligands, paying special attention to several apparently strained interactions that may favor the transition state for hydride transfer. Hypothetical models are presented for the binding of 7,8-dihydrofolate in the Michaelis complex and for the transition state complex. PMID- 2185836 TI - 31P NMR measurements of the ADP concentration in yeast cells genetically modified to express creatine kinase. AB - Rabbit muscle creatine kinase has been introduced into the yeast Saccharomyces cerevisiae by transforming cells with a multicopy plasmid containing the coding sequence for the enzyme under the control of the yeast phosphoglycerate kinase promoter. The transformed cells showed creatine kinase activities similar to those found in mammalian heart muscle. 31P NMR measurements of the near equilibrium concentrations of phosphocreatine and cellular pH together with measurements of the total extractable concentrations of phosphocreatine and creatine allowed calculation of the free ADP/ATP ratio in the cell. The calculated ratio of approximately 2 was considerably higher than the ratio of between 0.06 and 0.1 measured directly in cell extracts. PMID- 2185837 TI - Interaction of the Escherichia coli Gal repressor protein with its DNA operators in vitro. AB - The binding of Escherichia coli Gal repressor to linear DNA fragments containing two binding sites (OE and OI) within the gal operon was analyzed in vitro with quantitative footprint and mobility-shift techniques. In vivo analysis of the regulation of the gal operon [Haber, R., & Adhya, S. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 9683-9687] has suggested the role of a regulatory "looped complex" mediated by the association of Gal repressor dimers bound at OE and OI. The binding of Gal repressor to a single site can be described by a model in which monomer and dimer are in equilibrium and only the dimer binds to DNA. At pH 7.0, 25 mM KCl, and 20 degrees C, the binding and dimerization free energies are comparable, suggesting that the equilibrium governing the formation of dimers may be important to regulation. The two intrinsic binding constants, delta GI and delta GE, and a constant describing cooperativity, delta GIE, were determined by footprint titration analysis as a function of pH, [KCl], and temperature. Only at 4 and 0 degrees C was delta GIE negative, signifying cooperative binding. These results are thought to be due to a weak dimer to tetramer association interface. delta GE and delta GI had maximal values between pH 6 and pH 7. The dependence of these constants on [KCl] corresponded to the displacement of approximately 2 ion equiv. The temperature dependence could be described by a change in the heat capacity, delta Cp, of -2.3 kcal mol-1 deg-1. Mobility-shift titration experiments conducted at 20 and 0 degrees C yielded values for delta GIE that were consistent with those resolved from the footprint analysis. Unique values of delta GIE were determined by analysis of mobility-shift titrations of Gal repressor with wild-type operator subject to the constraint that delta GE = delta GI: a procedure that eliminates the need to simultaneously analyze wild-type titrations with titrations of OE- and OI- operators. PMID- 2185838 TI - The anti-Shine-Dalgarno region in Escherichia coli 16S ribosomal RNA is not essential for the correct selection of translational starts. AB - Plasmid pPM114, which contains the Escherichia coli 16S rRNA gene under control of a T7 promoter, was linearized upstream of the 3' end of the gene and used in an in vitro transcription assay to yield a 16S rRNA lacking about 30 nucleotides at its 3' end. This truncated 16S rRNA was assembled into 30S subunits which contain the full complement of 30S proteins, including S21, but were impaired in their capacity to associate to the 50S subunits. This impairment was paralleled by a decrease in their protein synthesis activity under the direction of natural or artificial messengers. However, although the anti-Shine-Dalgarno sequence was missing, the initiation step was not specifically affected, and the mutated ribosomes could initiate translation at the correct start sites. This supports previous suggestions that the translational efficiency and the selection of translational starts are not solely controlled by the Shine-Dalgarno interaction. A novel interpretation of the role of protein S21 is also proposed which is independent of the activation by this protein of the base-pairing potential of the anti-Shine-Dalgarno sequence of 16S rRNA. PMID- 2185839 TI - Subcloning, characterization, and affinity labeling of Escherichia coli glycinamide ribonucleotide transformylase. AB - Glycinamide ribonucleotide transformylase (GAR TFase; EC 2.1.2.2) has been purified 70-fold to apparent homogeneity from Escherichia coli harboring an expression vector encoding the purN gene product, GAR TFase. The protein is a monomer of Mr 23,241 and catalyzes a single reaction. Steady-state kinetic parameters for the enzyme have been obtained. The structural requirements for cofactor utilization have been investigated and found to parallel those of the multifunctional avian enzyme. The enzyme was inactivated with the affinity label N10-(bromoacetyl)-5,8-dideazafolate in a stoichiometric and active-site-specific manner. The ionization state of the cofactor analogue in the enzyme-cofactor complex appears to require the dissociation of the proton at N3 of the pyrimidine within the complex. PMID- 2185840 TI - Importance of domain closure for homotropic cooperativity in Escherichia coli aspartate transcarbamylase. AB - The importance of the interdomain bridging interactions observed only in the R state structure of Escherichia coli aspartate transcarbamylase between Glu-50 of the carbamoyl phosphate domain with both Arg-167 and Arg-234 of the aspartate domain has been investigated by using site-specific mutagenesis. Two mutant versions of aspartate transcarbamylase were constructed, one with alanine at position 50 (Glu-50----Ala) and the other with aspartic acid at position 50 (Glu 50----Asp). The alanine substitution totally prevents the interdomain bridging interactions, while the aspartic acid substitution was expected to weaken these interactions. The Glu-50----Ala holoenzyme exhibits a 15-fold loss of activity, no substrate cooperativity, and a more than 6-fold increase in the aspartate concentration at half the maximal observed specific activity. The Glu-50----Asp holoenzyme exhibits a less than 3-fold loss of activity, reduced cooperativity for substrates, and a 2-fold increase in the aspartate concentration at half the maximal observed specific activity. Although the Glu-50----Ala enzyme exhibits no homotropic cooperativity, it is activated by N-(phosphonoacetyl)-L-aspartate (PALA). As opposed to the wild-type enzyme, the Glu-50----Ala enzyme is activated by PALA at saturating concentrations of aspartate. At subsaturating concentrations of aspartate, both mutant enzymes are activated by ATP, but are inhibited less by CTP than is the wild-type enzyme. At saturating concentrations of aspartate, the Glu-50----Ala enzyme is activated by ATP and inhibited by CTP to an even greater extent than at subsaturating concentrations of aspartate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185841 TI - Multiple replacements at position 211 in the alpha subunit of tryptophan synthase as a probe of the folding unit association reaction. AB - Equilibrium and kinetic studies on the folding of a series of amino acid replacements at position 211 in the alpha subunit of tryptophan synthase from Escherichia coli were performed in order to determine the role of this position in the rate-limiting step in folding. Previous studies [Beasty, A. M., Hurle, M. R., Manz, J. T., Stackhouse, T., Onuffer, J. J., & Matthews, C. R. (1986) Biochemistry 25, 2965-2974] have shown that the rate-limiting step corresponds to the association/dissociation of the amino (residues 1-188) and carboxy (residues 189-268) folding units. In terms of the secondary structure, the amino folding unit consists of the first six strands and five alpha helices of this alpha/beta barrel protein. The carboxy folding unit comprises the remaining two strands and three alpha helices; position 211 is in strand 7. Replacement of the wild-type glycine at position 211 with serine, valine, and tryptophan at most alters the rate of dissociation of the folding units; association is not changed significantly. In contrast, glutamic acid and arginine dramatically decelerate and accelerate, respectively, both association and dissociation. The difference in effects is attributed to long-range electrostatic interactions for these charged side chains; steric effects and/or hydrogen bonding play lesser roles. When considered with previous data on replacements at other positions in the alpha subunit [Hurle, M. R., Tweedy, N. B., & Matthews, C. R. (1986) Biochemistry 25, 6356-6360], it is clear that beta strands 6 (in the amino folding unit) and 7 (in the carboxy folding unit and containing position 211) dock late in the folding process. PMID- 2185842 TI - cis-syn thymine dimers are not absolute blocks to replication by DNA polymerase I of Escherichia coli in vitro. AB - Both Escherichia coli DNA polymerase I (pol I) and the large fragment of pol I (Klenow) were found to bypass a site-specific cis-syn thymine dimer, in vitro, under standard conditions. A template was constructed by ligating d(pCGTAT[c,s]TATGC), synthesized via a cis-syn thymine dimer phosphoramidite building block, to a 12-mer and 19-mer. The site and integrity of the dimer were verified by use of T4 denV endonuclease V. Extension of a 15-mer on the dimer containing template by either pol I or Klenow led to dNTP and polymerase concentration dependent formation of termination and bypass products. At approximately 0.15 unit/microL and 1-10 microM in each dNTP, termination one prior to the 3'-T of the dimer predominated. At 100 microM in each dNTP termination opposite the 3'-T of the dimer predominated and bypass occurred. Bypass at 100 microM in each dNTP depended on polymerase concentration, reaching a maximum of 20% in 1 h at approximately 0.2 unit/microL, underscoring the importance of polymerase binding affinity for damaged primer-templates on bypass. Seven percent bypass in 1 h occurred under conditions of 100:10 microM dATP:dNTP bias, 1% under dTTP bias, and an undetectable amount under either dGTP or dCTP bias. At 100 microM in each dNTP, the ratio of pdA:pdG:pdC:pdT terminating opposite the 3'-T of the dimer was estimated to be 37:25:10:28. Sequencing of the bypass product produced under these conditions demonstrated that greater than 95% pdA was incorporated opposite both Ts of the dimer and that little or no frame shifting took place.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2185843 TI - Giant liposomes as model membranes for immunological studies: spontaneous insertion of purified K1-antigen (poly-alpha-2,8-NeuAc) of Escherichia coli. AB - A flow chamber has been constructed to use giant liposomes (diameter 5-50 microns) as model membranes for immunological studies and other experiments involving the interaction with water-soluble compounds. As an example of immunological importance, the insertion of purified K-antigen from Escherichia coli K1 has been studied. Despite its large hydrophilic part (poly-alpha-2,8 NeuAc), which is capped at its potential reducing end with phosphatidic acid acting as a lipid anchor group, this water-soluble material is readily incorporated into liposomal membranes of dimyristoylphosphatidylcholine (DMPC). The incorporation has been proven by immunofluorescence using a FITC-labeled monoclonal anti-K1-IgG. Without the lipid residue, however, no binding of poly alpha-2,8-NeuAc to the liposomes has been observed. This could be shown by using colominic acid, an oligomeric form of alpha-2,8-NeuAc with free reducing ends instead of purified K1-antigen. The possibility for further manipulation of this model system has been shown by using a poly-alpha-2,8-NeuAc cleaving enzyme (endoneuraminidase). The function of the endoneuraminidase has been proven by showing no binding of the antibody after enzyme treatment of K1-bearing liposomes as well as by rapid loss of fluorescence of a previously bound FITC-antibody. PMID- 2185844 TI - Partition of parinaroylphosphatidylethanolamines and parinaroylphosphatidylglycerols in immiscible phospholipid mixtures. AB - Partitioning of two parinaroyl phosphatidylethanolamines and two parinaroyl phosphatidylglycerols between solid and fluid phase phospholipids was examined. Fluorescence quantum yields and fluorescence polarization measurements were used to calculate Ks/fp, the solid to fluid partition coefficient of each probe (Sklar, L.A., Miljanich, G.P. and Dratz, E.A. (1979) Biochemistry 18, 1707-1716). In the immiscible mixture dipalmitoylphosphatidylcholine and dilinoleylphosphatidylcholine, both 1-palmitoyl-2-trans parinaroylphosphatidylethanolamine and 1-palmitoyl-2 transparinaroylphosphatidylglycerol partitioned preferentially into solid phase lipid with mean Ks/fp values (calculated from quantum yields) of 3.4 +/- 1.5 and 2.1 +/- 0.7, respectively. In contrast, 1-oleoyl-2-cis parinaroylphosphatidylethanolamine and 1-oleoyl-2-cis parinaroylphosphatidylglycerol partitioned preferentially into fluid phase lipid in the same model system with mean Ks/fp values (calculated from quantum yields) of 0.44 +/- 0.26 and 0.16 +/- 0.07, respectively. Fluorescence polarization data on the same four parinaroyl phospholipids in mixtures of solid-phase dimyristoylphosphatidyl ethanolamine and fluid-phase dilinoleoylphosphatidylglycerol were similar to those obtained in the immiscible phosphatidylcholine system, demonstrating that the partitioning of these probes is not strongly dependent on head group. Knowledge of the partition properties of these fluorescent probes is relevant to use of these probes in investigation of the phase behavior of Escherichia coli inner membrane lipids, since phosphatidylethanolamine and phosphatidylglycerol species account for approximately 95% of these lipids. PMID- 2185845 TI - Modification of glycophorin A during oxidation of erythrocyte membrane. AB - Human erythrocyte ghosts were oxidized with tert-butyl hydroperoxide and subsequently treated with tritiated borohydride to label the membrane proteins modified during the membrane oxidation. From the ghosts, oxidized-and-tritiated glycophorin A was isolated and characterized. No intermolecular cross-links were observed as analyzed by sodium dodecylsulfate gel electrophoresis. But, the number of lysine residues was significantly reduced and susceptibility to proteinases such as trypsin, chymotrypsin and pronase was lower than that of control glycophorin A. Trypsinization of the oxidized-and-tritiated glycophorin A gave insoluble and soluble trypsin fragments. After dansylation, N-terminal amino acids of the trypsin-fragments were determined. Dansyl amino acids from the insoluble trypsin fragments were not identical with those from control insoluble counterparts in the membrane-spanning region of glycophorin A molecule. Fractionation by gel filtration of dansyl-soluble trypsin fragments, and the N terminal amino acid analysis of the fractionated peptides indicated that the peptides derived from the glycosylated region located in the outside of the membrane matrix were identical with those from control soluble counterparts. The results suggest that the glycosylated outside region of glycophorin A was modified only slightly but the hydrophobic membrane-spanning region was extensively modified during membrane oxidation, most likely by oxidized lipids. PMID- 2185846 TI - Injury-induced vesiculation and membrane redistribution in squid giant axon. AB - Injury of isolated squid giant axons in sea water by cutting or stretching initiates the following unreported processes: (i) vesiculation in the subaxolemmal region extending along the axon several mm from the site of injury, followed by (ii) vesicular fusions that result in the formation of large vesicles (20-50 micron diameter), 'axosomes', and finally (iii) axosomal migration to and accumulation at the injury site. Some axosomes emerge from a cut end, attaining sizes up to 250 microns in diameter. Axosomes did not form after axonal injury unless divalent cations (Ca2+ or Mg2+) were present (10mM) in the external solution. The requirement for Ca2+ and the action of other ions are similar to that for cut-end cytoskeletal constriction in transected squid axons (Gallant, P.E. (1988) J. Neurosci. 8, 1479-1484) and for electrical sealing in transected axons of the cockroach (Yawo, H. and Kuno, M. (1985) J. Neurosci. 5, 1626-1632). Axosomes probably consist of membrane from different sources (e.g., axolemma, organelles and Schwann cells); however, localization of axosomal formation to the inner region of the axolemma and the formation dependence on divalent cations suggest principal involvement of cisternae of endoplasmic reticulum. Patch clamp of excised patches from axosomes liberated spontaneously from cut ends of transected axons showed a 12-pS K+ channel and gave indications of other channel types. Injury-induced vesiculation and membrane redistribution seem to be fundamental processes in the short-term (minutes to hours) that precede axonal degeneration or repair and regeneration. Axosomal formation provides a membrane preparation for the study of ion channels and other membrane processes from inaccessible organelles. PMID- 2185847 TI - Glucose- and concentration-dependence of noradrenalin effects on electrical activity in mouse pancreatic beta cells. AB - The effects of a wide range of noradrenalin (NA) concentrations (10(-11)-10(-4) M) on the membrane potential and on the glucose-induced electrical activity were investigated with microelectrodes in microdissected mouse islets. In the presence of 11.1 mM glucose, the beta cells exhibited a repetitive activity. NA at more than 10(-7) M induced a rapid hyperpolarization followed by a silent depolarization, then by the appearance of a slowed pace of repetitive activity (dose-dependent effects). NA at less than 10(-7) M did not markedly affect the electrical activity; it only induced a dose-dependent increase in the degree of activity with no change of the potential levels. The glucose-dependence of these effects were then investigated. In the absence of glucose, 10(-8) and 10(-6) M NA did not affect the resting membrane potential. Non-stimulatory glucose concentrations (2.8-7.3 mM) progressively decreased the membrane potential. 10( 8) M NA did not affect it, while 10(-6) M NA induced a dose-dependent and long lasting hyperpolarization. In the presence of stimulatory glucose concentrations (7.3-30 mM) the degree of activity increased, 10(-8) M NA induced a slight leftward shift and 10(-6) M NA a slight rightward shift of the dose-response curve. PMID- 2185848 TI - Kinetics of insulin binding and kinase activity of the partially purified insulin receptor from human skeletal muscle. AB - The kinetics of insulin binding and kinase activity of soluble, partially purified insulin receptors from human skeletal muscle are considered. An equilibrium for insulin binding was obtained within 2 h at 37 degrees C. At lower temperatures the equilibrium for insulin binding was less clearly defined. Dissociation of 125I-labelled insulin was incomplete unless an excess amount of unlabelled insulin was added. Insulin-stimulatable autophosphorylation of the 95 kDa subunit was verified by gel electrophoresis. The kinase activity was measured with the synthetic polypeptide poly(Glu-Tyr(4:1] as a phosphoacceptor. The insulin receptor kinase activity correlated significantly (r = 0.92, P less than 0.0001) to the concentration of high-affinity insulin binding sites in the eluate. Autophosphorylation of the insulin receptor was necessary for the activation of the receptor kinase. When activated the receptor kinase activity was stable for at least 60 min at 21 degrees C with a pH optimum of approx. 7.8, similar to the pH optimum for insulin binding. The non-ionic detergent Triton X 100 inhibited the sensitivity of the receptor kinase to insulin. Insulin stimulated the Vmax of the kinase reaction about 3-fold, decreased the Km for ATP from 35 +/- 5 microM (mean +/- S.E.) to 8 +/- 1 microM (P less than 0.02) and induced a positive cooperativity to ATP with an increase in the Hill coefficient from 1.00 +/- 0.02 to 1.37 +/- 0.07 (P less than 0.05). According to the Hill plots, insulin itself showed no cooperativity with respect to receptor binding or kinase activation. PMID- 2185849 TI - Hypercortisolism and its possible neural bases. AB - As is clear from the pages of this journal, biological psychiatrists remain fascinated by the phenomenon of dexamethasone (DEX) resistance and the hypercortisolism of various neuropsychiatric disorders. The mere existence of the endocrine abnormalities attests to the biological reality of these disorders. Furthermore, progress continues in using the occurrence of these endocrine defects as both diagnostic and prognostic markers of disease subtypes. Progress has also been made in understanding the mechanisms underlying the endocrine defects. The adrenocortical axis is vastly complex, involving multiple hypothalamic-releasing factors under CNS control, shifting pituitary and adrenal sensitivies to hormonal signals, and feedback regulation at all three levels. What defects within this system produce DEX resistance and hypercortisolism? In this paper, we review data suggesting that the endocrine problems is, at least in part, neural in nature. Drawing upon a rodent literature, we will also suggest some models by which this can occur. The hypercortisolism found in cases of affective disorders, anorexia nervosa, Alzheimer's disease, among the very aged or the chronically stressed, is not a uniform phenomenon. Basal cortisol concentrations can be elevated in all or part of the circadian cycle. Resistance to glucocorticoid (GC) feedback inhibition (as typically demonstrated by DEX resistance) can occur; the resistance can be complete, or occur as early escape from DEX suppression. Finally, elevated basal cortisol concentrations and DEX resistance can occur independently of each other. Until the end of this review, we will conveniently refer to these variants of adrenocortical hyperactivity as "hypercortisolism." In addition, rather than using the term "hypercortisolism" for the rat, we will use "hyperadrenocorticism" (as they secrete corticosterone, rather than cortisol). PMID- 2185850 TI - Captopril as an antidepressant? Effects on the learned helplessness paradigm in rats. AB - Several clinical investigations have suggested that captopril, an angiotensin converting enzyme inhibitor (ACEI), currently used as an antihypertensive agent, exhibited anti-depressant properties in humans. The present experiment was evaluated for potential antidepressive activity of captopril on the learned helplessness paradigm in rats. Captopril (8, 16, 32 mg/kg/day, IP) induced a reversal of escape deficits but did not affect significantly the motor activity, suggesting that this effect was not due to motor stimulation. This antidepressant like activity was comparable to that of imipramine (16, 32 mg/kg/day, IP). Naloxone (0.5; 1 mg/kg, IP) blocked the effect of captopril (16 mg/kg, IP) in this test. These results suggest that an opioid mediation could be responsible at least in part for its behavioral effect. PMID- 2185851 TI - A microcomputer-based system for measurement of ultrasound imaging. AB - A microcomputer-based imaging system for acquisition and analysis of ultrasound has become available. In order to fulfill the clinical demands, the more complete and detailed examinations required, the more sophisticated ultrasound instrumentation costs. This paper demonstrates the simplicity of a personal computer to provide an inexpensive method for measurement on video images from a real-time ultrasound scanner. The process data obtained on ATL 600 and found acoustic intensity histograms to be of value in differential diagnostic purposes. It includes spatial filtering, gray scale expansion, contrast enhancement, color index shifting and histogram analysis, etc. It allows the computer graphics to be superimposed on the ultrasound video images and permits subsequent analysis. To perform the manipulations and programming one of commercially available software and hardware are outlined and encouraged. PMID- 2185852 TI - [Effects of crush syndrome on insulin receptor interactions in cells]. AB - Comparative study of binding insulin receptor mononuclears, erythrocytes and hepatocytes of crush-syndrome revealed great difference in these parameters. In the early period of crush-syndrome (stress period insulin insufficiency hyperglycemia, insulin resistance, decrease in the activity of insulin binding in the mononuclears and increase in the activity of erythrocytes. By the 6 hour crush-syndrome (toxemic period) hyperinsulinemia, hyperglycemia, are observed as well as prolongation of the decrease in the activity of insulin binding of mononuclears. PMID- 2185853 TI - [Ultrastructure of the epithelial cells of the duodenum at the early stages of experimental Escherichia infection]. AB - Ultrastructural changes of duodenal epitheliocytes were studied at the period from 15 minutes to 24 hours after inoculation using the model of experimental esherichiosis. The results obtained allow to determine the succession of ultrastructural changes and dynamics of adenylate cyclase activity of epithelial cells, involvement of endocrine cells in the pathological process. Combination of the certain morphological and cytochemical reactions and their dynamics allowed to make conclusions about typical ultrastructural changes in epitheliocytes at the early stages of experimental esherichiosis. PMID- 2185854 TI - Chitosan--as a biomaterial. AB - Chitosan [a (1----4) 2-amino-2-deoxy-beta-D-Glucan] is a unique polysaccharide derived from chitin. Several attempts have been made to use this biopolymer in biomedical field. The use of this material in the development of hemodialysis membranes, artificial skin, drug targetting and other applications are discussed. It appears, this novel biomolecule, biodegradable, and biocompatible, find applications in substituting or regenerating the blood/tissue interfaces. This polysaccharide having structural characteristics similar to glycosaminoglycans, seems to mimic their functional behaviour. PMID- 2185855 TI - Natural history of peritonitis post-peritoneal dialysis (PPPD). PMID- 2185856 TI - A mathematical analysis of the U-shaped hybrid artificial pancreas--a novel insulin release rate equation. AB - While most artificial pancreases rely mainly on diffusive transport of solutes, Reach et al. (1) proposed a U-shaped device which combines diffusive and convective transports to shorten the lag time between insulin release and a rise in blood glucose concentration. This paper presents a mathematical model which predicts well the performance of the U-shaped hybrid artificial pancreas for both square-wave and ramp glucose stimulations. The model uses a novel insulin secretion equation, and a possible inhibition mechanism regulating insulin secretion is also discussed. PMID- 2185858 TI - The chemical basis of morphogenesis. 1953. PMID- 2185857 TI - Subtyping male alcoholics by family history of alcohol abuse and co-occurring psychiatric disorder: a bi-dimensional model. AB - Six studies of 568 alcoholics in treatment are summarized to illustrate the interactive effects of familial alcoholism, other forms of family psychopathology and the lifetime prevalence of additional psychiatric disorder on the onset and course of male alcoholism. A family history of alcoholism as well as additional co-occurring psychiatric syndromes were associated with (1) earlier onsets of problem drinking, (2) a more virulent course and (3) greater heterogeneity of psychopathology among first degree relatives. A bi-dimensional method of classifying male alcoholics is proposed which combines a family history of abusive drinking and the presence or absence of co-morbid psychiatric disorders. Implications for the clinical researcher and practitioner are briefly discussed. PMID- 2185859 TI - A mathematical theory of natural and artificial selection--I. 1924. PMID- 2185860 TI - Evolution in Mendelian populations. 1931. PMID- 2185861 TI - A quantitative description of membrane current and its application to conduction and excitation in nerve. 1952. PMID- 2185862 TI - On the dominance ratio. 1922. PMID- 2185863 TI - A logical calculus of the ideas immanent in nervous activity. 1943. PMID- 2185864 TI - The development and use of digital subtraction angiography. PMID- 2185865 TI - Final report of the general clinical results of the British Institute of Radiology fractionation study of 3F/wk versus 5F/wk in radiotherapy of carcinoma of the laryngo-pharynx. AB - The 10 year follow-up of a clinical trial involving the comparison of 3F/wk versus 5F/wk in radiotherapy of squamous cell carcinoma of the larynx and hypopharynx has now been completed. The trial involved an intake of 734 patients between 1966 and 1975. The classification of all patients has been revised to conform with the latest TNM publication. A reduction in total dose was made for 3F/wk compared with 5F/wk. This varied between 13% and 11% in centres treating over 3 weeks and 6 weeks, respectively. No statistically significant differences have been found between the two arms (3F/wk versus 5F/wk) of the trial in any of the main group analyses. A number of sub-group analyses relating to survival, tumour-free and laryngectomy-free rates and to the comparison of acute or late normal-tissue radiation damage have also been performed. No differences have been found that could be considered to be statistically significant in relation to the particular sub-group. Previous interim reports suggested minor differences in sub group analyses between the 3F/wk and 5F/wk regimes in this trial; these have diminished now that the full follow-up data are available. This trial has provided evidence on which clinicians may base their choice between either a 3F/wk fractionation regime or a conventional 5F/wk treatment protocol in the treatment of carcinoma of the laryngo-pharynx. PMID- 2185866 TI - Anatomical variations of the carotid bifurcation: implications for digital subtraction angiography and ultrasonography. AB - Intravenous digital subtraction angiography was used to determine prospectively the positional variations of the common carotid bifurcation in 100 consecutive patients with clinically suspected arteriosclerotic disease. The most common position (97/200, 48.5%) of the external carotid artery was anteromedial to the internal carotid artery. Position of the external carotid artery anterolateral to the internal carotid artery was noted in 26/200 (13%) bifurcations, but this anatomical variant was more common on the right (21/100) than on the left (5/100) (p less than 0.01). Practical implications may be drawn from this study. For digital subtraction angiography, the left anterior oblique view has to be considered the projection of choice and the right common carotid bifurcation is less likely to be adequately displayed than the left one; for duplex ultrasonography, optimal visualization is obtained from a posterolateral orientation of the transducer. PMID- 2185867 TI - [The first period in the history of the Institute for General Biology]. AB - Of the history of the Institute for General Biology, School of Medicine, Comenius University, the study deals with the first period, namely the years 1923-1945. The institute greatly benefited from the activities of Prof. MUDr. Zdenek Frankenberger who established it and was its Head in the first year of its existence. From 1925 till 1943 the institute was directed by Prof. MUDr. Jozef Florian Babor. Professor Babor's main interest was focused on malacology and he achieved international reputation in this field of zoology. He investigated the flora and fauna of Slovakia, was engaged in limnology, and cooperated with Professor Frankenberg in the field of anthropology and primatology. Over these years, prof. Vojtech Nabelek and MUDr. Bohumil Krajnik greatly contributed to the activities and development of the institute along with Prof. Babor. The Institute for General Biology was already in the first period of its existence reknown not only for its teaching activities but was also internationally appreciated in the medical, biological and historiographic community. PMID- 2185869 TI - Isolation and immunochemical characterization of fractions from membranes of Aspergillus fumigatus with protease activity. AB - Two fractions exhibiting acid protease activity (AFPI and AFPII) were isolated by extraction of membrane vesicles of Aspergillus fumigatus with Triton X-100. These two fractions produced single bands in both polyacrylamide and sodium dodecyl sulfate polyacrylamide gel electrophoresis and showed apparent molecular weights of 73,000 and 43,000, respectively. Molecular weights determined by gel filtration in the absence and presence of Triton X-100 and sedimentation velocities in analytical ultracentrifugation indicated hydrophobic characteristics, since both fractions readily aggregated and complexed with Triton X-100; both exhibited elevated enzyme activities in the presence of Triton X-100. Carbohydrate content was 93% for AFPI and 85% for AFPII. The enzymatic fractions demonstrated different pH optima in the acid range as well as different temperature stabilities. Both protease fractions cross reacted in double immunodiffusion, while in crossed immunoelectrophoresis both demonstrated five precipitin peaks, each with similar patterns. AFPI demonstrated two additional precipitin peaks in crossed immunoelectrophoresis. As determined by crossed immunoaffinoelectrophoresis, the protease fractions demonstrated galactose and mannose residues. In biotin-avidin enzyme-linked immunosorbent assay both fractions reacted with allergic bronchopulmonary aspergillosis and aspergilloma sera. It can be concluded that two fractions with protease activity of A. fumigatus reported here may be of significance in Aspergillus-induced diseases. PMID- 2185868 TI - Inducible cellular responses to ultraviolet light irradiation and other mediators of DNA damage in mammalian cells. AB - Both naturally occurring and carcinogen-induced tumors display not only point mutations in cellular oncogenes but also more complex changes in cellular oncogenes and other cellular genes. For this and other reasons, it seems likely that DNA damage in mammalian cells can induce alterations in gene expression that may have both short and long term consequences in the target cell. The purpose of this review is to summarize current available information on inducible responses to UV-irradiation and other mediators of DNA damage in mammalian cells, and to provide some working hypotheses. We have divided these responses into three time frames, immediate (0-12 hours), early (12-48) and late (beyond 48 hours). Immediate responses include the action of DNA repair enzymes, some of which are induced as a consequence of DNA damage, and transient inhibition of DNA synthesis. Within the past few years considerable evidence has accumulated that during this immediate period there is increased expression of certain cellular oncogenes, proteases and proteins whose functions remain to be identified. It is of interest that the expression of some of these genes is also induced by certain growth factors, tumor promoters and heat shock. Alterations in gene expression during the subsequent "early" period (12-48 hrs.) have not been studied in detail, but it is during this period that one can detect increased replication of several types of viruses in cells that harbor these viruses. We have examined in detail the induction of asynchronous polyoma DNA replication (APR) in a rat fibroblast cell line carrying integrated copies of this DNA. We have obtained evidence that UV-irradiation of these cells leads to the synthesis of a 40 kd protein, within the first 1-24 hrs after irradiation, that binds to a specific sequence TGACAACA in the regulatory region of polyoma DNA. We suggest that this protein acts together with other proteins to induce APR and that this serves as a useful model for understanding the mechanisms responsible for amplification of cellular genes, a phenomenon often seen in malignant tumors. Finally, we discuss how the events occurring during the immediate and early periods following DNA damage might lead to late effects in the target cell that are stable and contribute to the genotype and phenotype of some of the progeny of these cells that are destined to become tumor cells. PMID- 2185870 TI - Determination of peptidyl dipeptidase activity in 24 bacterial species. AB - Of 24 bacterial species examined for lisinopril refractive peptidyl dipeptidase activity, only 8 contained activity. Activity in Pseudomonas maltophilia was more than fourfold higher than that of any other species. Pseudomonas maltophilia may be unique among bacteria in possessing high peptidyl dipeptidase activity that is both EDTA inhibitable and lisinopril resistant. PMID- 2185871 TI - An improved method for the rapid isolation of chromosomal DNA from Mycoplasma spp. AB - A method is described for the rapid isolation of chromosomal deoxyribonucleic acid from species of the genus Mycoplasma. The method involves incubation of washed cells at elevated temperature in the presence of an ionic detergent, chelating agents, and proteinase K prior to the removal of residual protein and ribonucleic acid with ribonuclease and chloroform. It results in a good yield of high molecular weight material that is shown to be free of endogenous nuclease and substantially free of protein or ribonucleic acid contamination without the use of phenol. The isolated DNA is shown to be an excellent substrate for restriction endonuclease digestion and ligation with T4 DNA ligase. PMID- 2185872 TI - A biometric study of higher alcohol production in Saccharomyces cerevisiae. AB - A hundred strains of Saccharomyces cerevisiae were examined for the ability to produce higher alcohols. In the strains tested the production of higher alcohols was found to be an individual strain characteristic and, as such, was statistically significant. The characteristics of the strains used (flocculation ability, foaming ability, killer character, and non-H2S production) were found to be uncorrelated to isobutanol and isoamyl alcohol production, whereas the production of high levels of n-propanol was found to be related to inability to produce H2S. This, in turn, suggests a link to methionine biosynthesis. PMID- 2185873 TI - Overview. Current status of clinical trials. AB - The five areas outlined in this discussion represent a large proportion of the current environment for clinical trials. They identify significant obstacles to the advancement of knowledge in clinical oncology. There is no single or overriding solution to the health care system and its problems with funding and access or to the antiintellectual mood of our times. Continuous efforts to improve science are needed now more than ever. Adequate accession to trials is an ongoing issue. These problems are compounded by the ethical issues created by today's opportunities. The etiquette of territoriality is no less daunting. Each of these affects the environment in which trials are conducted, and each deserves the serious attention of all of us. Some suggestions for action have been made. The need for resolution is obvious. PMID- 2185874 TI - Clinical trials. Concerns of the patient and the public. AB - This paper reviews what is known about attitudes toward clinical trials among patients and the public, the use of surrogates (physicians and patients) to determine whether a clinical trial is acceptable, and other empiric data available on this issue. Other concerns related to the conduct of clinical trials are explored including strategies for assuring the best quality of care for patients involved in these studies. The author suggests several actions to improve public understanding and participation in clinical trials including the development of new educational strategies for presenting information to the public, development of mechanisms for documenting and communicating the quality of care received by patients in clinical trials, and the implementation of quality-of-life assessments in clinical trials to provide an additional outcome measure for clinical situations in which the survival differences between treatments are insignificant. The limited information that is available suggests that the concerns of patients and the public must be addressed if clinical trials are to be successful in recruitment of adequate numbers of subjects to answer important clinical research questions. PMID- 2185875 TI - Ethical considerations in randomized controlled clinical trials. PMID- 2185876 TI - Breakout I. Ethical considerations. PMID- 2185877 TI - Nontraumatic focal lesions of the spleen: assessment of imaging and clinical evaluation. AB - Fifty-nine cases of nontraumatic splenic disease were reviewed to evaluate the roles of clinical findings, computed tomography, ultrasound, and radionuclide scanning in diagnosis and management. Patient groups included lymphoma (30 patients), infarct (11 patients), abscess (9 patients), cyst (5 patients), hemangioma (3 patients), and hamartoma (1 patient). In no case were clinical findings alone sufficient to diagnose a splenic lesion. Clinical and laboratory manifestations were nonspecific in all groups. Moreover, no radiologic study reliably diagnosed splenic lymphoma or leukemia. All other focal splenic lesions were consistently diagnosed noninvasively. Cross-sectional imaging was more useful than radioisotope scanning, and often provided adjunctive diagnosis of extrasplenic pathology. The superior detail, spatial resolution, and sensitivity of computed tomography made it the single most valuable diagnostic modality. PMID- 2185878 TI - Differential expression of ros oncogene in primary human astrocytomas and astrocytoma cell lines. AB - Overexpression of oncogenes has been associated with the pathogenesis of some human cancers. The ros oncogene, which encodes a putative receptor with tyrosine kinase activity, has been recently shown to be specifically expressed in high levels in human astrocytoma and glioblastoma cell lines. Using transcription mapping analysis, we surveyed 25 primary astrocytomas of all histological grades, including glioblastomas, and failed to demonstrate elevated expression of ros in these tumors. This difference between the cell lines and the primary tumors may be due to dilution of the ros-positive clones by larger populations of ros negative cells in the primary tumors or to induction of ros oncogene when the tumors are adapted to tissue culture. PMID- 2185879 TI - Inverse correlation between expression of multidrug resistance gene and N-myc oncogene in human neuroblastomas. AB - Genomic amplification of N-myc is an important prognostic indicator in neuroblastoma. The tumors with amplified N-myc are initially sensitive to chemotherapy but often acquire resistance to therapy, recur, and ultimately kill the patients. We measured amplification and expression of N-myc and expression of mdr-1 in 35 surgically resected neuroblastomas, before acquisition of drug resistance and in 4 recurrent tumors resistant to chemotherapy. The mdr-1 mRNA expression was found to be inversely correlated with the N-myc expression. The mdr-1 gene expression was at a low level in advanced stage and histologically undifferentiated neuroblastomas, the same group of tumors in which N-myc expression is elevated. A significantly better prognosis was noted in those patients whose tumors had a high level of mdr-1 expression and a low level of N myc expression. The role, if any, of increased expression of mdr-1 in the acquisition of multidrug resistance in neuroblastoma remains unclear. However, the aggressive clinical behavior associated with N-myc amplification and/or expression appears to be linked to down-regulation of mdr-1 expression. PMID- 2185880 TI - Amplification of the c-myc oncogene during progression of radiation-induced rat skin tumors. AB - Evaluation of a large panel of radiation-induced rat skin tumors of diverse size and histological type revealed a correlation between c-myc copy number and tumor size. Both the frequency and degree of c-myc gene amplification were increased in large compared to small carcinomas, but none of the sarcomas examined showed c myc amplification. Serial biopsies of individual tumors exhibited similar trends of increasing c-myc copy number in later biopsies. In one regressing tumor, the c myc gene copy number paralleled the growth rate of the tumor during growth and regression. The average time required from tumor appearance to significant gene amplification was close to the average period between tumor appearance and the onset of rapid growth. The data suggest that, rather than being a target gene for the direct early effects of ionizing radiation, c-myc functions as a late-stage progression-related oncogene in this model system. PMID- 2185881 TI - Malignant lymphoma antigen expressed in nude mouse tumor cells derived from carcinogen-transformed Bloom's syndrome B-lymphoblastoid cell lines. AB - From nude mouse tumors, in which malignantly transformed Bloom's syndrome (BS) B lymphoblastoid cell lines were successfully transplanted into s.c. tissues, we have detected strong expression of malignant lymphoma (ML)-associated antigen on the cell surface, by using diluted sera of ML patients and indirect immunofluorescence. Even though carcinogen-treated BS B-lymphoblastoid cell lines expressed various types of cancer antigens (ML, ovarian cancer, stomach cancer, lung cancer, liver cancer, etc.) on the cell membrane as a mixed population (Y. Shiraishi and H. Soma, Proc. Natl. Acad. Sci. USA, 85:8211-8215, 1988), the finding that BS malignant cells originating from nude mouse tumors expressed specific ML-associated antigen seemed significant for ML diagnosis. BS nude mouse tumors were successively transplantable from nude mice to nude mice (100%). Histopathological studies using an electron microscope demonstrated that most tumor cells in s.c. tissues of nude mice were lymphoid malignant cells. Gel electrophoresis and Western blotting analyses demonstrated that the antigen which characterized ML was a single band (Mr 97,000) and did not cross-react with the sera of other cancer patients or with normal sera. Chromosome analysis showed that the cell clones with ML-associated antigen had marker chromosomes involving t(6;?)(p25;?),t(9;?)(q34;?), del(10)(p13),t(12;14)(q24;q11). The expression of ML associated antigen was also discussed in relation to the marker chromosomes. PMID- 2185882 TI - Immune response to progressor variants derived from transfection of an ultraviolet radiation-induced C3H mouse regressor tumor cell line with activated Harvey-ras oncogene. AB - Skin cancers induced in mice by UV radiation often exhibit a regressor phenotype. In order to determine how tumors escape the immune defenses of the normal immunocompetent host, we sought to isolate progressor variants from a UV radiation-induced C3H mouse regressor fibrosarcoma cell line, UV-2240, by transfection with an activated Ha-ras oncogene. A cotransfection protocol using pSV2-neo DNA, which confers resistance to the antibiotic G418, was used to select transfected cells. Injection of Ha-ras-transfected UV-2240 cells s.c. into immunocompetent C3H mice produced tumors in four of 36 animals. In contrast, UV 2240 cells transfected with pSV2-neo DNA alone or mock transfected with CaPO4 did not produce tumors in normal C3H mice. DNAs from cell lines established from Ha ras-induced tumors contained unique Ha-ras sequences in addition to those sequences endogenous to UV-2240 cells. However, the Ha-ras-induced progressor variants did not overexpress the Mr 21,000 protein. The Ha-ra-induced progressor variants produced experimental lung metastasis in both normal C3H and nude mice, although they induced more lung nodules in nude mice than in normal C3H mice. In addition, all four Ha-ras-induced progressor variants produced significantly more experimental lung metastases in nude mice than did the parent UV-2240 cell line. However, both the parental UV-2240 cell line and the Ha-ras-induced progressor variants expressed similar levels of H-2Kk and H-2Dk antigens and were immunologically cross-reactive, as determined by in vitro cytotoxic T-lymphocyte and in vivo immunization-challenge assays. These results indicate that the progressor phenotype of the Ha-ras-induced tumor variants is not due to loss of tumor-specific transplantation or Class I major histocompatibility complex antigens. This implies that some tumor cells can escape the immune defenses of the normal immunocompetent host by mechanisms other than loss of tumor-specific transplantation and Class I major histocompatibility antigens. PMID- 2185884 TI - Production of endothelin in human cancer cell lines. AB - Endothelin (ET)-1 is a vasoconstrictor peptide derived from endothelial cells and now known to be a local regulator of vascular tonus. Recent studies, however, have revealed that ET-1 functions also as growth factor in various cells. By using a specific ET-1 radioimmunoassay, immunoreactive (IR) ET-1, ranging from 4.2 to 150 pM (minimum detectable amount, 4.0 pM), was detected in 13 of 42 human cancer cell lines. The frequencies of IR-ET-1 production and its concentrations were high in mammary, pancreatic, and colon carcinoma cell lines. IR-ET-1 produced by cancer cells possessed the same molecular size as synthetic ET-1 and also had ET-1-like biological activity. Moreover, Northern blot analysis revealed bands corresponding to ET-1 mRNA in cancer cell lines, indicating that IR-ET-1 produced by cancer cells is a product of the ET-1 gene. Since ET-1 in the spent media is present in a sufficient amount to stimulate cellular growth, we sought ET-1 receptors in four pancreatic carcinoma cell lines and human skin fibroblasts. No ET-1 receptors were detected in the pancreatic carcinoma cell lines. However, human skin fibroblasts possessed a large number of ET-1 receptors. This finding raises the possibility that ET-1 produced by cancer cells plays a modulatory role in the growth of stromal cells surrounding cancer cells. PMID- 2185883 TI - Identification of a nuclear matrix-associated region of the c-myc protooncogene and its recognition by a nuclear protein in the human leukemia HL-60 cell line. AB - A nuclear matrix (NM)-associated region (MAR) of the protooncogene c-myc is identified in a human leukemia cell line (HL-60). A binding assay between isolated NM and 32P-end-labeled c-myc fragments in the presence of unlabeled competitors was used, and a 3'-end DraI/DraI fragment of 172 base pairs containing the first of the two polyadenylation [poly(A)] signals was identified as an in vitro MAR. Direct detection of endogenous c-myc fragments remaining NM bound after restriction digestion was used, and an in vivo MAR has been identified as the ClaI/EcoRI 1.4-kilobase pair fragment containing the 172-base pair in vitro MAR fragment. In addition, a nuclear protein (Mr = 25,000, p25) demonstrating preferential binding to the 172-base pair c-myc MAR has been identified and partially purified. This protein is diminished in the nuclei of the cells induced by phorbol ester to undergo macrophage differentiation. Footprint analysis shows that p25 binds to two regions of the 172-base pair fragment. One contains the first of two poly(A) addition signals and a topo II box-like sequence, and the other (AATTTCAATCCTAGTA) is 17 base pairs downstream of the first poly(A) signal. PMID- 2185885 TI - Factors regulating the activity of striatal neurons: new perspectives from in situ hybridization histochemistry. AB - 1. The basal ganglia contain a variety of putative peptide neurotransmitters. In situ hybridization allows changes in the levels of the mRNAs encoding these neuropeptides to be assessed at the cellular level of resolution. 2. Alterations in the activity of pathways within the basal ganglia of the rat produce distinct effects on the different neuropeptide mRNAs. 3. The evidence, where available, suggests that mRNA levels provide an index of peptide turnover. 4. This approach has consequently revealed much new information on the regulation of neuronal activity in the basal ganglia. PMID- 2185886 TI - [The end of Dr. Emil Holuba's life based on his last letters]. PMID- 2185887 TI - Hepatitis delta virus: cis and trans functions required for replication. PMID- 2185888 TI - Dual regulation of meiosis in yeast. AB - The two regulatory pathways appear to come together at the IME1 gene. It is clearly regulated by mating type and induced by starvation as well. Overexpression of IME1 completely overcomes MAT defects but may not circumvent all nutritional control. Kassir et al. (1988) found that overexpression of IME1 allowed sporulation in the presence of glucose and nitrogen. They also have found a meiotic level of message in temperature-sensitive cdc25 diploids shifted to high temperature in rich medium (Simchen and Kassir, 1989). Smith and Mitchell (1989) found that overexpression of IME1 induced an early meiotic event (recombination) in rich medium, but later meiotic events did not occur (i.e., they detected no spore formation). Mitchell (personal communication) has suggested that the difference may be due to differences in the amount of nitrogen present in the two experiments. Thus, while it is clear that IME1 is a necessary positive regulator of meiosis, responding both to mating type and nutritional conditions, it is not clear if it is sufficient. It is possible that other genes are involved in the response to starvation. One interpretation is that a separate nutritional control is exerted for events starting with meiosis I. Much of the regulatory pathway that allows yeast cells to enter meiosis has been determined. As in the case in many sensory transduction pathways, the initial signal for starvation is not yet known, nor is the nature of the proposed downstream phosphorylated effector. Given the power of yeast molecular genetics, answers to both these questions seem attainable. Another area that remains unclear is the difference between responses to nitrogen starvation versus carbon source. Many of the experiments discussed above do not address this question. The strategies used by yeast may be utilized in the developmental decisions used by other, more complex eukaryotes. Certainly several of the gene products involved in nutritional control in yeast have homologies in mammalian systems. For example, the human H-ras gene can substitute for yeast RAS; the relationship is sufficiently close that dominant Ha-ras mutations that inhibit CDC25 have been found (Powers et al., 1989). Furthermore, these dominant Ha-ras mutations have the appropriate phenotype in mammalian cells, suggesting the presence of a CDC25 like protein. Although the major components of mating type control appear to have been defined, the mechanism of the RME1-IME transcriptional control remains to be determined.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2185889 TI - The expression of influenza virus hemagglutinin in the pancreatic beta cells of transgenic mice results in autoimmune diabetes. AB - Insulin-dependent diabetes mellitus results from the autoimmune destruction of the insulin-producing beta cells of the pancreatic islets. The target antigen(s) involved in this immunopathological process has not been identified. Our strategy was to determine whether expression of a novel surface antigen by murine pancreatic beta cells would result in insulin-dependent diabetes mellitus. We have generated lines of transgenic mice (RIP-HA) that express the hemagglutinin of the A/Japan/305/57 strain of influenza virus on their insulin-producing beta cells. Hyperglycemia developed in mice derived from all three founders at a frequency varying from 13% to 27%, and was associated with lymphocytic infiltration of the islets and a humoral response against beta cell antigens, including hemagglutinin. These results suggest that the RIP-HA mice should provide a useful system in which to study the cellular interactions involved in the induction of self-tolerance and autoimmunity. PMID- 2185890 TI - Genetic changes in skin tumor progression: correlation between presence of a mutant ras gene and loss of heterozygosity on mouse chromosome 7. AB - Initiation of tumorigenesis in mouse skin can be accomplished by mutagenesis of the H-ras gene by treatment with chemical carcinogens. A mouse model system has been developed to study the additional genetic events that take place during tumor progression. Skin carcinomas were induced in F1 hybrid mice exhibiting restriction fragment length polymorphisms at multiple chromosomal loci. Analysis of loss of heterozygosity in such tumors showed that imbalance of alleles on mouse chromosome 7, on which the H-ras gene is located, occurs very frequently in skin carcinomas. The chromosomal alterations detected, which included both nondisjunction and mitotic recombination events, were only seen in tumors that have activated ras genes. We conclude that gross chromosomal alterations that elevate the copy number of mutant H-ras and/or lead to loss of normal H-ras are a consistent feature of mouse skin tumor development. PMID- 2185891 TI - Analysis of wild-type and rad50 mutants of yeast suggests an intimate relationship between meiotic chromosome synapsis and recombination. AB - The RAD50 gene of S. cerevisiae is required during meiosis for both recombination and chromosome synapsis and is also required for repair of double strand breaks during vegetative growth. We present below the isolation and analysis of several types of rad50 mutants. We show that null mutations block both meiotic recombination and formation of synaptonemal complex (SC) at early stages, while nonnull mutations block both processes at intermediate stages. These observations suggest that recombination and SC formation involve a series of intimately related events. Furthermore, all rad50 mutants block formation of tripartite SC structure but permit other aspects of SC development, i.e., formation of axial cores. In light of this and other observations, the meiotic and mitotic defects of rad50 mutants can be accounted for economically by the proposal that meiotic recombination, meiotic chromosome pairing, and vegetative DNA repair all use a common chromosomal homology search that involves RAD50 function. PMID- 2185892 TI - Yeast centromere binding protein CBF1, of the helix-loop-helix protein family, is required for chromosome stability and methionine prototrophy. AB - The centromere and its binding proteins constitute the kinetochore structure of metaphase chromosomes, which is crucial for the high accuracy of the chromosome segregation process. Isolation and analysis of the gene encoding a centromere binding protein from the yeast S. cerevisiae, CBF1, are described in this paper. DNA sequence analysis of the CBF1 gene reveals homology with the transforming protein myc and a family of regulatory proteins known as the helix-loop-helix (HLH) proteins. Disruption of the CBF1 gene caused a decrease in the growth rate, an increase in the rate of chromosome loss/nondisjunction, and hypersensitivity to the antimitotic drug thiabendazole. Unexpectedly, the cbf1 null mutation concomitantly resulted in a methionine auxotrophic phenotype, which suggests that CBF1, like other HLH proteins in higher eukaryotic cells, participates in the regulation of gene expression. PMID- 2185893 TI - Molecular interactions between the protein products of the neurogenic loci Notch and Delta, two EGF-homologous genes in Drosophila. AB - Genetic analyses have raised the possibility of interactions between the gene products of the neurogenic loci Notch and Delta, each of which encodes a transmembrane protein with EGF homology. To examine the possibility of intermolecular association between the products of these two genes, we studied the effects of their expression on aggregation in Drosophila S2 cells. We find that Notch-expressing cells form mixed aggregates specifically with cells that express Delta and that this process is calcium dependent. In addition, we show that Notch and Delta can associate within the membrane of a single cell, and further, that they form detergent-soluble intermolecular complexes. Our analyses suggest that Notch and Delta proteins interact at the cell surface via their extracellular domains. PMID- 2185894 TI - Destabilization of ionized Ca2+ homeostasis in excitatory amino acid neurotoxicity: antagonism by glycosphingolipids. PMID- 2185895 TI - [Combined use of ultrasound and radiodiagnostic methods in the diagnosis of posterior dislocation of the lens]. AB - In a case record the authors present an account on a patient with an opaque media of the left eye on account of seclusion and occlusion of the pupil. The cause of the unilateral chronic uveitis was elucidated by ultrasonic examination with visualization type A. The cause was a calcified lens dislocated into the vitreous body and fixed to the posterior wall of the eye. The finding was confirmed by a negative X-ray picture and positive finding of a small foreign body with high density on CT. Dislocation of the lens occurred after a blow on the left eye during boxing 15 years before the patient sought medical assistance on account of a painful practically blind eyeball. PMID- 2185896 TI - [Aging of the brain, Alzheimer's disease and the most frequent vascular dementias]. PMID- 2185897 TI - [Beta 2-microglobulin and tumors of the central nervous system]. AB - In 60 patients with tumours of the central nervous system (50 intracranial, 10 intraspinal) the beta 2-microglobulin in serum and cerebrospinal fluid was examined. The frequency of pathological finding was in both examined fluids considerable and differed with regard to the type and site of the tumours; it was particularly high in intracranial gliomas (in serum 87.1%, in cerebrospinal fluid 74.2%). For comparison a group of 55 patients with multiple sclerosis was examined where the incidence of elevated beta 2-microglobulin was markedly lower (in serum 29.1%, in cerebrospinal fluid 20%). Normal values in serum and cerebrospinal fluid were obtained in 50 subjects without organic lesions of the nervous system. PMID- 2185898 TI - [70 years of the First Neurologic Clinic of Comenius University Medical School in Bratislava. The past, present and future]. PMID- 2185899 TI - [25 years of the Rehabilitation Institute for Cerebrovascular Diseases in Chotebor]. PMID- 2185900 TI - Carcinogen metabolism in cultured human tissues and cells. AB - A large number of chemical carcinogens require metabolic activation before they are biologically active. The metabolism of a few of these compounds has been investigated in cultured human tissues and cells and the metabolism has been compared with the metabolism in organs from experimental animals in which the compounds induce cancer. Generally, only quantitative differences could be observed between animal and human tissues. The development of new methods to detect carcinogen-DNA adducts makes it feasible to study and compare the metabolism in human and animal tissues of an increasing number of potential human carcinogens. Furthermore, construction of cell lines, expressing the human forms of the carcinogen metabolizing enzymes, by biotechnology provides a new model to study the metabolism and to monitor for genetic markers in the same cells. PMID- 2185901 TI - Increased drug resistance following retroviral gene transfer of a chimeric P enolpyruvate carboxykinase (GTP)-bacterial O6-alkylguanine-DNA alkyltransferase gene into NRK cells. AB - Transfection of the Escherichia coli ada gene coding for O6-alkylguanine-DNA alkyltransferase results in expression of ada in mammalian cells and transmission of nitrosourea resistance to cells lacking alkyltransferase activity. We have used a replication-incompetent retrovirus to transfer into mammalian cells a chimeric gene consisting of 548 bp of the promoter-regulatory region of the gene for P-enolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) linked to ada. The PEPCK promoter was used because it is inducible and highly expressed in liver and kidney cells both in vitro and in vivo. After retrovirus infection of the rat kidney cell line, NRK, intact proviral DNA was integrated into the genome of cloned cells. Individual NRK clones produced up to 200 units/mg protein of bacterial alkyltransferase activity compared to 65 units/mg protein of mammalian alkyltransferase in the parent cell line. Transcription of ada mRNA originating from the PEPCK promoter was induced with Bt2cAMP or dexamethasone and the combination caused a 4-fold increase in ada mRNA while total alkyltransferase activity was induced up to 2-fold. NRK clones expressing ada had up to 2.0-fold increased resistance to 1,3-bis(2- chloroethyl)-1- nitrosourea. Thus, retroviral gene transfer of the PEPCKada chimeric gene allows efficient and inducible expression of ada with a resulting increase in alkyltransferase activity and nitrosourea drug resistance. This retrovirus may be used to study the role of alkyltransferase in repair of mutagenic DNA lesions in mammalian cells in vivo. PMID- 2185902 TI - A reassessment of methylcholanthrene transformation in the C3H10T1/2 cell culture system. AB - We previously demonstrated that four tumorigenic methylcholanthrene (MCA) transformed cell lines derived from C3H10T1/2 cells each contain a common G34--- T nucleotide alteration in the c-Ki-ras gene. In contrast, a non-tumorigenic MCA transformant does not contain this mutation. We have now examined 75 newly isolated MCA transformants of C3H10T1/2 cells for their degree of morphological transformation, the presence of the c-Ki-ras G34----T mutation, colony formation in soft agar, and tumorigenicity in nude mice. Although many of these new MCA transformants exhibit morphological characteristics indistinguishable from previously isolated tumorigenic MCA transformants, none contain the G34----T mutation in the c-Ki-ras gene. Only one newly isolated MCA transformant can grow in soft agar. Of 14 tested, none of the new MCA C3H10T1/2 transformants are tumorigenic in nude mice. PMID- 2185903 TI - The effects of methylnitrosourea (MNU) on natural killer (NK) cell cytotoxicity and cytokine production in rats. AB - Eight-week-old male Sprague-Dawley rats were exposed to the carcinogen methylnitrosourea (MNU) via gastric intubation at doses of either 10 or 20 mg/kg body wt. Rats were treated once a week for 4 weeks, then once every 2 weeks for 1 month, for a total of 6 treatments. MNU was found to exert no consistent significant immunosuppressive effects in vivo as measured by spleen natural killer (NK) cell cytotoxicity, interleukin-2 (IL-2) production by splenic lymphocytes and prostaglandin E2 (PGE2) production by adherent peritoneal macrophages. In contrast, splenic NK cell cytotoxicity and IL-2 production of MNU treated rats were actually elevated at several of the later sampling periods. PGE2 production was also elevated in MNU-treated rats in the later sampling periods. Body weights of MNU-treated rats were markedly decreased as early as 4 weeks following the initial MNU treatment. This suppression persisted throughout the study. The most dramatic change in organ weights was seen in the thymus. Thymus weights of all MNU-treated rats were significantly decreased 1 day after treatment and persisted for 4 weeks. By the 60 day sampling period, thymus weights were not significantly different from controls. However, by 120 and 180 days, thymus weights again were significantly lowered in those rats receiving MNU. These changes in thymus weights were accompanied histologically by initial cortical thinning and progressive loss of cortical thymocytes followed by the appearance of hyperplastic and neoplastic cells. It thus appears that the carcinogenic effect of MNU is not related to a depression of the immune surveillance system, at least as measured by NK cell activity. PMID- 2185904 TI - In vivo viscoelastic behavior in the human aorta. AB - To characterize the viscoelastic properties of the human aorta in vivo, the pressure-diameter relation was determined in the abdominal aorta in 15 subjects. Diameter was measured noninvasively with a highly sensitive ultrasonic displacement meter, while intra-aortic pressure was measured with a catheter tip micromanometer inserted from the femoral artery. The frequency-dependent changes in the pressure-strain modulus (Ep) of the aorta and the phase lag of diameter to pressure were calculated by frequency analysis of these wave forms at the mean blood pressure of 109 mm Hg. The Ep and the phase lag at the fundamental frequency component (1.2 +/- 0.3 Hz, mean +/- SD) were (1.52 +/- 0.57) x 10(6) dyne/cm2 and -6.7 degrees +/- 2.1 degrees, respectively. Although the phase lag at the fundamental frequency was in good agreement with the published in vitro data, the calculated phase lags above the second harmonic were inconsistent, which was probably due to the nonlinearity in the pressure-diameter relation. To separate the effect of this nonlinearity, analysis was conducted with a model consisting of a static nonlinear component representing the elasticity and a dynamic linear component representing the viscosity. This method of analysis revealed that the phase lag due to the viscous component provided relatively flat frequency response to the 10th harmonic. It was confirmed that the aortic wall viscosity showed no apparent difference between the in vivo and the in vitro experimental conditions. PMID- 2185905 TI - Chirality. Clinical pharmacokinetic and pharmacodynamic considerations. PMID- 2185908 TI - Furosemide (frusemide). A pharmacokinetic/pharmacodynamic review (Part I). AB - Furosemide (frusemide) is a potent loop diuretic used in the treatment of oedematous states associated with cardiac, renal and hepatic failure, and for the treatment of hypertension. Therapy is frequently complicated by apparently erratic systemic availability from the oral route and from unpredictable responses to a given dosage. The exact mechanism of action is not fully understood, but furosemide is believed to act at the luminal surface of the ascending limb of the loop of Henle by inhibiting the active reabsorption of chloride. The response to a given dosage is modulated by the fluid and electrolyte balance of the individual. Acute and delayed tolerance has been demonstrated both in animals and in man, and is postulated to be due to the intervention of homeostatic mechanisms influencing fluid and electrolyte balances. Furosemide is delivered to its site of action by active secretion via the nonspecific organic acid pump. Comparisons between the observed diuresis/saluresis and plasma furosemide concentrations, urinary excretion rates and renal clearance found either negative or no correlations with plasma drug concentration but significant correlations with urine measurements. Response is related to the concentration of the drug in urine rather than in plasma. The most common adverse reactions attributable to furosemide therapy are essentially extensions of the therapeutic effects (i.e. fluid and electrolyte disturbances). The pharmacokinetic behaviour of furosemide is marked by a large degree of variability, derived from differences within and between both subjects and study protocols. Part of this variability can be attributed to differences in organ function, which is important in view of the types of patients treated with furosemide. On the other hand, a large proportion remains as inter- and intrasubject variation. The bioavailability of furosemide from oral dosage forms is highly variable. The poor bioavailability has been hypothesized to be due to the poor solubility of the compound, site-specific absorption, presystemic metabolism and/or other unknown mechanisms. Furosemide is highly bound to plasma proteins, almost exclusively to albumin. Although the drug is insoluble in water and favours partitioning into fatty tissue, the high degree of plasma protein binding restricts the apparent volume of distribution at steady-state to values within a multiple of 2 to 5 times the plasma volume. Furosemide has two documented metabolites--furosemide glucuronide and saluamine (CSA). The first is an accepted metabolic product, whereas the status of CSA as a metabolite is highly controversial.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2185907 TI - Pharmacokinetics and metabolism of mitoxantrone. A review. AB - Mitoxantrone, a cytotoxic anthracenedione derivative, has given clinical evidence of beneficial activity in breast cancer, lymphoma and leukaemia. Several different mechanisms of action have been suggested to account for this. In addition to intercalation, biological effects such as electrostatic interactions with DNA, DNA-protein cross-links, immunosuppressive activities, inhibition of topoisomerase II, prostaglandin biosynthesis and calcium release have been described. Various methods of drug monitoring in biological fluids and tissues are available: the highest sensitivity has been achieved with high performance liquid chromatography with electrochemical detection, radioimmunoassay and enzyme linked immunosorbent assay. Early pharmacokinetic studies of mitoxantrone in experimental animals using radioactive material showed an extensive tissue distribution and a long terminal plasma half-life. The best fit for the plasma concentration-time curve in humans is achieved in a 3-compartment model. All studies reported a short absorption half-life of between 4.1 and 10.7 minutes, with the distribution phase being between 0.3 and 3.1 hours. In contrast, the values of the terminal half-life are quite variable, ranging from 8.9 hours to 9 days. Differences might be attributed to assay sensitivity, number and weighting of data points beyond 24 hours and coadministration drugs. Many studies showed a very large volume of distribution with sequestration of mitoxantrone in a deep tissue compartment. In autopsy studies, relatively high tissue concentrations have been measured in liver, bone marrow, heart, lung, spleen and kidney. Bile is the major route for the elimination of mitoxantrone, with lesser amounts excreted in the urine. Several metabolites have been separated, 2 of which were identified as the monocarboxylic and dicarboxylic acid derivatives. Mitoxantrone is usually administered by rapid intravenous infusion at 3-weekly intervals; other regimens include continuous infusion, daily repeated doses or weekly administration. In peritoneal carcinosis, the pharmacological advantage of intraperitoneal administration is clear. The optimal regimen for different disease categories with respect to efficacy and side-effects remains to be determined in future clinical trials. PMID- 2185909 TI - The role of erythropoietin in the anaemia of chronic disease in rheumatoid arthritis. AB - We reviewed studies on the role of erythropoietin (Epo) in the anaemia of chronic disease (ACD) in rheumatoid arthritis (RA). A relatively impaired Epo response to the anaemia was found in a number of studies although in others serum Epo level was the same as in other types of anaemia. Some arguments are found in favor of a reduced bone marrow-Epo sensitivity although these reflect results mainly from in vitro experiments. It is not yet established whether bone marrow macrophage Epo production is impaired in ACD. In two cases Epo administration to RA patients resulted in increased erythropoiesis. It was concluded that impaired Epo production or reduced bone marrow Epo sensitivity might be associated with ACD but it is not certain whether these factors are causally linked with ACD or side phenomena of RA disease activity. Future Epo treatment in RA and ACD will possibly solve this question. PMID- 2185906 TI - Clinical pharmacokinetics of imipramine and desipramine. AB - The pharmacokinetics of imipramine and desipramine have been extensively investigated with recent studies designed to understand sources of intersubject variability and to study discrete clinical populations rather than healthy volunteers. Sources of intersubject variability in pharmacokinetics are both genetic (oxidative phenotype) and environmental. Oxidative phenotype has an important impact on first-pass metabolism. In individuals with poor metabolism, systemic availability for imipramine is increased. Intrinsic clearance of desipramine is reduced 4-fold in individuals with poor metabolism. Recent pharmacokinetic studies in diverse patient populations such as the depressed elderly, children and alcoholics have revealed decreased clearance of imipramine in the elderly and increased clearance of both imipramine and desipramine in chronic alcoholics. In at least a third of the population, nonlinear pharmacokinetics of desipramine may be observed at steady-state plasma concentrations above 150 micrograms/L. These nonlinear changes in desipramine pharmacokinetics are not associated with age or sex, but are associated with higher desipramine 2-hydroxydesipramine concentration ratios. Hydroxylated metabolites of imipramine and desipramine may possess both antidepressants and cardiotoxic activity but their formation is rate limited and plasma concentrations tend to follow the parent compound with little accumulation. The potent cardiovascular effects of the hydroxymetabolites may be particularly relevant for the elderly and in acute overdose. PMID- 2185910 TI - HLA antigens in Yugoslav population with rheumatoid arthritis. AB - The antigens of HLA-DR locus were determined in 127 patients with rheumatoid arthritis and in 175 healthy persons. The frequency of HLA-DR1 antigen was discovered in 45% of the patients and in 22.3% of the examinees from the control group (p less than 0.001). The relative risk is 2.84. 69% of the patients were seropositive. The HLA-DR4 antigen was found in 34% of the patients and in 21% of the healthy examinees (p less than 0.05). The relative risk is 1.91. The rheumatoid factor was determined in 70% of the patients with this antigen. PMID- 2185911 TI - Pulmonary hypertension in connective tissue disease. Clinical analysis of sixty patients in multi-institutional study. AB - Clinical features and prognosis of sixty patients with connective tissue disease accompanied by pulmonary hypertension (PH) (26 MCTD, 20 SLE, and 14 PSS) reported retrospectively by multi-institutions were compared. Though the obtained data were incomplete and lacking in uniformity, no significant difference in the clinical features among the three diseases were observed except high incidence of pulmonary fibrosis and low % VC in PSS and PH patients. Statistically significant difference, however, was observed between live and dead patients of three diseases gathered in post sternal pain, pulmonary diastolic murmur, right ventricular hypertrophy on ECG and mean pressure of pulmonary artery. Higher incidence of anti-nRNP antibody was observed in SLE with PH and PSS with PH patients than with the general population. A quicker occurrence of PH and shorter survival time were observed in MCTD patients with PH than in SLE and PSS patients with PH. PMID- 2185912 TI - The use of tricyclic antidepressants for the treatment of intractable pain. PMID- 2185913 TI - Diagnosis and treatment of polymyositis and dermatomyositis. PMID- 2185914 TI - Diagnostic and surgical arthroscopy. AB - Arthroscopy has developed dramatically over the last 10 years. Surgeons now have the ability to perform many procedures arthroscopically in almost any joint that previously required arthrotomy. This has resulted in notable benefits in decreased morbidity, earlier return to full activity, and decreased cost. Considerable experimental work is being done to apply arthroscopic procedures to joints other than the knee and shoulder in order to develop new procedures to successfully treat disorders in these areas. PMID- 2185915 TI - Osteoporosis: prevention and treatment. PMID- 2185916 TI - Diagnosis and monitoring of spondylarthropathy. PMID- 2185917 TI - The biologic actions of extracellular adenosine triphosphate. AB - The study of the biologic effects of extracellular ATP is rapidly progressing from cataloging the integrated biologic responses of isolated tissues to characterizing the biochemical basis of signal transduction in isolated cells. Clearly, many fundamental issues remain; these include the classification of receptor subtypes, identification of defined or new signal-transduction pathways, generation of specific high-affinity ligands for the various ATP receptor subtypes, and ultimately, the development of protocols for the identification, isolation, cloning, and physicochemical characterization of the receptor moities per se. Such work will be essential for developing selective ATP-receptor antagonists. Such antagonists, in turn, will facilitate evaluation of the role of these receptors in physiological and/or pathological processes. A possible therapeutic role for drugs selective for these receptors is suggested by the critical pathophysiological roles of the human cell types (phagocytic leukocytes, vascular endothelial cells) known to express such receptors. The earlier, seminal work on the biologic actions of extracellular ATP was largely performed by smooth muscle physiologists and pharmacologists. With the expanding range of, and interest in, this topic, recent studies have been carried out largely by diverse groups of pharmacologists, neurobiologists, physiologists, and biochemists. Not surprisingly, these various scientists often investigate certain aspects of extracellular ATP action from different perspectives, using the specialized tools and methods of their respective disciplines. Hopefully, by integrating these interdisciplinary perspectives on the biologic actions of extracellular ATP, there will be rapid progress in this field during the next few years. PMID- 2185918 TI - Dental treatment demands among patients in Tanzania. AB - The dental treatment demands of 824 patients attending regional dental clinics were recorded. Overall 86% of the patients sought treatment for pain, ranging from 77% to 97% in the different clinics. Caries was the main cause of pain. The proportion of patients with demands for aesthetics was 5%, prosthetics 2%, and check up 3%. The data indicated a need for emergency care. The type of curative treatment needed, mainly extractions, could well be performed by dental auxiliaries. Since the data was collected from patients among whom many visited the clinics in the late stages of painful oral diseases, it is assumed that it reflects only the tip of an iceberg that represents a much larger dormant demand (want) for emergency care among the population. Any strategy aiming to be effective in improving oral health should at least meet the emergency dental needs of the population. Consequently there is a definite need of data on dental treatment demands and wants for adequate planning of dental health care systems in their infancy in countries with limited financial resources. PMID- 2185919 TI - Nucleic acid probes as potential tools in oral microbial epidemiology. AB - The present review deals with genetic tools in the microbial diagnostic laboratory, types of nucleic acid probes, their construction and cloning, hybridization reactions, their sensitivity and specificity, and their advantages and limitations. The nucleic acid probes seem to possess a number of advantages over traditional diagnostic methods. DNA, RNA, and oligonucleotide probes are expected to have increased impact on our understanding of the pathogenesis and the treatment of infectious inflammatory periodontal diseases. In addition, these probes have potential application in epidemiological studies of oral microorganisms. However, the limitations of the probes must be kept in mind, and newly developed probes must be controlled with respect to the critical issues of sensitivity and specificity. PMID- 2185920 TI - Novel instrumentation for multifield time-lapse cinemicrography. AB - The most significant feature of the system that is described is its ability to image essentially simultaneously the growth of up to 99 single cells into macroscopic colonies, each in its own microscope field. Operationally, fields are first defined and programmed by a trained observer. All subsequent steps are automatic and under computer control. Salient features of the hardware are stepper motor-controlled movement of the stage and fine adjustment of an inverted microscope, a high-quality 16-mm cine camera with light meter and controls, and a miniature incubator in which cells may be grown under defined conditions directly on the microscope stage. This system, termed MUTLAS, necessitates reordering of the primary images by rephotographing them on fresh film. Software developed for the analysis of cell and colony growth requires frame-by-frame examination of the secondary film and the use of a mouse-driven cursor to trace microscopically visible (4X objective magnification) events. PMID- 2185921 TI - Interpreting chromosomal abnormalities using Prolog. AB - This paper describes an expert system for interpreting the standard notation used to represent human chromosomal abnormalities, namely, the International System for Human Cytogenetic Nomenclature. Written in Prolog, this program is very powerful, easy to maintain, and portable. The system can be used as a front end to any database that employs cytogenetic notation, such as a patient registry. PMID- 2185922 TI - Automated access to a large medical dictionary: online assistance for research and application in natural language processing. AB - Online dictionaries can be important tools for research and application in natural language processing. This paper describes work with a machine-readable version of "Dorland's Illustrated Medical Dictionary". First the characteristics of the dictionary are briefly described, and then the complex process of converting the tape to an online interactive dictionary is discussed. The results of several experiments in automatically deriving information from the online dictionary are presented, and the paper ends with a discussion of the use of the online dictionary as a tool in the development of a natural language processing system designed for the biomedical domain. PMID- 2185924 TI - [Body mass as a factor determining the social status of male red voles]. PMID- 2185923 TI - Echocardiography in coronary artery disease. AB - Echocardiography has a major role in the evaluation of patients with CAD. To obtain the maximal amount of information using this technique, certain basic principles relating to regional myocardial mechanics during ischemia and flow function relations are required. In addition, a detailed knowledge of cardiac anatomy and the three-dimensional orientation of the heart within the chest cavity is required to access meaningful information from two-dimensional planes. Furthermore, skill is also required in acquiring data in proper imaging planes and in separating true (actual pathology) from the false (artifacts, etc.). Echocardiography is not a "mature" technology. It is still developing and it is sometimes difficult to keep up with the advances. However, keeping abreast of these developments is essential to fully exploit the advantages of this technique. In addition, knowledge of the ever-changing aspects of CAD is required in order to correctly interpret visual information in context of a particular patient. Finally, more clinical studies are needed to further define the role of echocardiographic techniques in patients with CAD. PMID- 2185925 TI - [Epidemiologic studies of the recognition of the preclinical phase of type I diabetes in school children]. AB - Sera of 4208 schoolchildren in Ulm and surrounding areas (1916 boys, 2292 girls; mean age 13.9 [7-21] years) were analysed for the presence of cytoplasmatic islet cell antibodies (ICA). ICA were demonstrated in 44 children (1.05%). Complement fixing ICA (CF-ICA) were found in six of them, insulin autoantibodies (IAA) in seven. The early phase of insulin response in the intravenous glucose tolerance test was below the 1st percentile of normal controls in two of the ICA-positive children. In the course of the subsequent 6-9 months the ICA disappeared in half of the previously positive children. In the two with abnormal glucose tolerance tests ICA, CF-ICA and abnormal insulin secretion persisted during the observation period of 9 months. In another CF-ICA-positive schoolchild insulin response to the glucose tolerance test fell below the 1st percentile after 6 months. These results indicate that, even in an unselected group of children, persisting ICA and CF-ICA are high-risk markers for abnormal insulin secretion, which precedes the onset of type I diabetes. PMID- 2185926 TI - [Malignant lymphoma--diagnosis and staging]. PMID- 2185927 TI - Comparison of the mechanisms of action of insulin and triiodothyronine on the synthesis of cerebroside sulfotransferase in cultures of cells dissociated from brains of embryonic mice. AB - The effect of low (physiological) concentrations of insulin (2 and 20 ng/ml) and L-triiodothyronine (T3) were studied on two myelin-related enzymes: (1) the 3' phosphoadenosine-5'-phosphosulfate:cerebroside sulfotransferase (CST, EC 2.8.2.11) catalyzing the production of sulfatide, and (2) the myelin enzyme, 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP, EC 3.1.4.3.7) in myelinogenic cultures of cells dissociated from embryonic mouse brain. Insulin treatment (20 ng/ml) of the cells in the presence of serum increased CST activity at 18 and 25 days in vitro (DIV) by 86 and 211%, respectively. At 18 DIV and under the same conditions, CNP was significantly stimulated (95%) by high doses of insulin (2,000 ng/ml) only, while arylsulfatase A (EC 3.1.6.1) or cerebroside sulfatase activities, both of which are involved in sulfatide degradation, were unchanged. Thus, it can be assumed that the observed increase of the incorporation of [35S]O4 into sulfatide after insulin treatment of mixed cell cultures is the result of CST induction rather than a decreased catabolism. The level of CST activity in insulin-treated cells (20 ng/ml) in serum-free medium was also increased at 18 and 25 DIV by about 50 and 70%, respectively. Conversely, none of the insulin concentrations used in the absence of serum (even at high doses) had any effect, either at 18 or 25 DIV on CNP and ASA activities. The involvement of insulin in the regulation of sulfatide synthesis was further confirmed by dose response curves relating the activity of CST to hormone concentration in the medium. The increase in the activity of CST in insulin-treated cells was due only to the increase in the Vmax of this enzyme, suggesting that it may be attributed to enzyme induction. A study of kinetic parameters of CST indicated that there were no differences in pH optimum and Km values between control and induced enzyme. Further experiments using cycloheximide point to a direct effect of insulin on oligodendrocyte CST induction. Data similar to those described above for insulin were also obtained with T3. As for insulin, T3 stimulated the induction of CST but in serum-free medium only. This effect was prevented by cycloheximide. In addition, the induction of CST by T3 was blocked by actinomycin D. This was not the case for insulin. These results suggest that T3 and insulin act on CST by different mechanisms, i.e. at transcriptional and post translational levels, respectively. Apart from this, the insulin effect on CST activity was additive to that of T3.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2185928 TI - Chronological development of the fetal stomach assessed using real-time ultrasound. AB - To elucidate processes involved in the developing fetal stomach in utero, we examined chronological changes in maximum longitudinal and anteroposterior gastric dimensions in 618 fetuses from 16 to 41 weeks of gestation, using real time ultrasound. Three statistically critical points were evident at 26-27, 32 33, and 36-37 weeks of gestation. Both dimensions increased from 16-17 to 26-27 weeks, remained fairly constant between 26-27 and 32-33 weeks, increased again from 32-33 to 36-37 weeks, and then decreased from 36-37 weeks onwards. These findings suggest that there are four different phases underlying the development of gastric function in the human fetus, corresponding to the time-periods divided by the three critical points of gestational age. PMID- 2185929 TI - Increased renal echogenicity in the neonate. AB - We report data on newborn infants with increased renal echogenicity observed at the Division of Neonatal Intensive Care of Pavia during a five-year period. Review of 1600 abdominal ultrasonic evaluations revealed 103 newborn infants (56 females and 47 males, with birth weight from 560 to 3700 g and gestational age from 25 to 42 weeks) whose kidneys showed increased echogenicity. Three patients with infantile polycystic kidney disease, two with renal candidiasis, three with dysplastic kidney and two with renal vein thrombosis showed diffuse hyperechogenicity. Three patients with hemolytic-uremic syndrome showed cortical hyperechogenicity. Increased medullary echogenicity was observed in 90 infants with renal disease secondary to perinatal asphyxia. In 76 of these patients the evaluation of renal echogenicity and the renal function improved, while in the remaining 14 newborns the renal alteration persisted until death. PMID- 2185930 TI - Prediction of rebleeding in peptic ulcers by visual stigmata and endoscopic Doppler ultrasound criteria. AB - Following peptic ulcer hemorrhage, the ability to accurately determine those patients at highest risk of rebleeding relies on clinical and endoscopic criteria which are accurate in only a variable proportion of cases. In this study we have assessed prediction of rebleeding in peptic ulcers using a transendoscopic vascular detector (TVD) to compare the presence of a positive Doppler signal in relation to an ulcer base with visual stigmata of recent hemorrhage (SRH). Of 711 patients endoscoped for upper GI hemorrhage over an 18-month period 180 (25%) were found to have a peptic ulcer. One hundred and twenty-four had either minor or no SRH at the time of endoscopy, and none of these patients rebled. Fifty-six patients had a single peptic ulcer with either active hemorrhage, a visible vessel or adherent clot, and 22 were entered into the trial. Overall, 9 patients (41%) in this group rebled. Considering prediction of rebleeding, visible vessels had a sensitivity of 89% and specificity of 92% compared with a positive Doppler signal sensitivity of 87% and specificity of 86%. These results suggest that the TVD can predict rebleeding in peptic ulcers with an accuracy similar to that of endoscopic identification of a visible vessel. PMID- 2185931 TI - Transpapillary miniscopy and mini-biopsy of the pancreatic duct. AB - This paper reports on the new combined examination of peroral transpapillary fine caliber endoscopy (miniscope 0.5 mm in diameter) with mini-biopsy of the pancreatic duct in 10 patients and 19 surgical pancreas resection preparations. With this technique, endoscopic-retrograde inspection of the whole length of the pancreatic duct is possible without the need for papillotomy. In the case of pancreatic duct changes due to carcinoma of the pancreas, and chronic pancreatitis, the ductal lesions can be inspected. Furthermore, with the aid of a new mini-biopsy forceps (1.5 mm in diameter), material for histological evaluation can be much more efficiently obtained than was normally possible with conventional biopsy forceps (2.2 mm). This new endoscopic-bioptic technique promises to improve the diagnostic reliability in pancreatic duct lesions requiring clarification. PMID- 2185932 TI - Negative Haemoccult test in malignant and premalignant lesions of the colon, validation of the Haemoccult test with total colonoscopy. PMID- 2185934 TI - Circulating levels of placental protein 12 (PP 12) in diabetic pregnancy complicated by retinopathy. AB - Placental protein 12 (PP 12) is a soluble tissue antigen. Immunohistochemical studies have localized PP 12 in the placental syncytiotrophoblast, chorion and amnion, and also in the decidua. During normal pregnancy serum-PP 12 is already raised in the first trimester, there is then a peak at 18 weeks, a gradual fall until 32 weeks, and a moderate increase thereafter. The mean of the healthy control group at 18 weeks of pregnancy was 122.9 +/- 47.5 micrograms/l. The mean of the diabetic group with retinopathy at the same time was 192.2 +/- 78.8 micrograms/l. There was no significant difference between background retinopathy and the proliferative form of diabetic retinopathy. At all times during pregnancy the median values of PP 12 in diabetic pregnancies were significantly (p less than 0.01) above the control values. Increased PP 12 levels in diabetic pregnancy complicated by retinopathy are probably caused by decidual, placental and amniotic leakages. PMID- 2185933 TI - A nonlinear pharmacologic model of the acute effects of ozone on the human lungs. AB - A pharmacologic model describing the quantitative relationship between short-term exposure to ozone and pulmonary airway resistance is described. The model simulates the following processes: (1) removal of a fraction of inhaled ozone in the airways of the head; (2) ozone oxidation of membrane-bound fatty acids in the target tissue in the lower airways; (3) rupture of cell membranes, releasing inflammatory mediators into the intercellular space; (4) migration of inflammatory cells into the injured tissue, releasing additional mediators and thus amplifying the inflammatory effect of ozone in a positive feedback loop; (5) stimulation of irritant receptors by ozone directly and by inflammatory mediators leading to vagally mediated bronchoconstriction. Mathematically the model consists of a logistic equation determining losses in the head, and a set of four differential equations simulating the uptake of ozone in the target tissue and the ensuing inflammation and bronchoconstriction. The observed human response to ozone in chamber studies is nonlinear, and it was necessary to introduce a nonlinear feedback loop for inflammation in the model to replicate this. Despite limited data upon which to base the model, it successfully predicts the human response to ozone reported in a series of published short-term chamber studies and is superior to "effective dose" (the product of ozone concentration, minute ventilation, and exposure duration) used by other investigations to describe dose response relationships. Nonlinear multicompartment pharmacologic models such as this one can exhibit very complex behavior making the estimation of model parameters difficult, but they hold promise because the physiologic processes under study are themselves complex nonlinear phenomena. PMID- 2185935 TI - Insulin therapy on the peritoneal route: effects on glucose control in experimental insulin dependent diabetes. AB - To quantitate the degree of glycemic control in relation to insulin doses required on the peritoneal route of administration, insulin dependent diabetic dogs instrumented with chronic peritoneal and venous catheters and with access devices for serial peritoneal injections, were treated with regular insulin at random order as follows: (1) subcutaneous injections, (2) peritoneal injections, (3) continuous intravenous infusion, (4) continuous peritoneal infusion. Metabolic profiles were taken over 24 h after an average duration of treatment of 2 weeks and were compared to data obtained in nondiabetic animals. Insulin doses and postprandial increase in peripheral insulinemia were higher and glycemic control was worse on peritoneal vs. subcutaneous injection therapy. Glycemic control and insulin doses were identical between peritoneal and intravenous infusion regimes. Hyperinsulinemia was only seen during nighttime in intravenously infused animals. It is concluded that in accordance with the fast pharmacokinetics of peritoneally administered insulin, sufficient glycemic and insulinemic control can only be obtained on the peritoneal route, when the insulin is applied by means of pumps. PMID- 2185936 TI - Influence of polyethylene glycol (PEG) extraction on the C-peptide determination in sera from insulin-dependent diabetic patients with circulating insulin antibodies. AB - To investigate whether the unexpectedly high C-peptide levels in some insulin dependent diabetic (IDDM) patients are due to co-determination of proinsulin bound to circulating insulin antibodies, 36 randomly selected sera from IDDM patients were assayed for C-peptide immunoreactivity (CPR) after polyethylene glycol (PEG) extraction, preceding incubation with proinsulin binding antibodies (LAB + PEG) or without pretreatment of the sera. Recovery of proinsulin was checked by addition of 1 nmol/l proinsulin to all sera. Recovery was found to be 101.5 +/- 4.0%. The mean values of concentrations were significantly lower (p less than 0.001) after treatment with PEG and IAB + PEG compared to the untreated sera. There was also a significant difference (p less than 0.05) between sera extracted with PEG alone or after IAB + PEG-treatment. However, no correlation (p greater than 0.1) was found to bound insulin (total minus free insulin) or to insulin binding capacity (IBC) of the sera. If an antiserum is not available with very low cross-reactivity with proinsulin to determine human C-peptide then sera should not be extracted with PEG alone but after additional incubation with a proinsulin binding antiserum. In spite of the extraction in some cases unexplicably high C-peptide levels may still be expected. PMID- 2185937 TI - Autoantibodies against insulin (IAA), C-peptide (CAA), and glucagon (GAA) in new onset type 1 diabetic patients. AB - Autoantibodies against insulin, C-peptide, and glucagon were determined by radio binding assay in 63 new-onset Type 1 (insulin-dependent) diabetic patients as well as in 70 controls. Plasma peptide binding was determined by means of 125I labeled peptides and charcoal-dextran separation technique. Binding values exceeding the mean plus three standard deviations of the controls were considered as antibody-positive. Sixteen patients (25%) were positive for IAA, as 6 (10%) were positive for CAA and 2 (3%) for GAA. Of all control subjects, none were positive for either IAA or CAA, whereas 2 (2%) had GAA. The mean 125I-glucagon binding in the patients' group was, however, slightly enhanced and could be suppressed to normal values by excess unlabeled glucagon. The presence of IAA and/or CAA was significantly associated with more severe symptoms at diabetes manifestation. These results indicate that in new-onset Type 1 diabetics autoimmunity arises against all the insular peptides tested but is predominantly directed against those antigens secreted from the beta cells. Nevertheless, extremely low-binding GAA seem to be common in these patients. The determination of IAA/CAA might be useful in detecting a possible heterogeneity of Type 1 diabetes with regard to its clinical mode of manifestation. PMID- 2185938 TI - Humoral-mediated anti-islet cytotoxicity in diabetes-prone BB/OK rats--effect on beta-cell function and autologous islets. AB - The present study investigates whether sera from diabetic BB/OK rats impair beta cell-specific functions of rat pancreatic islets and whether humoral-mediated cytotoxicity in BB rat sera also affects the autologous islets of normoglycaemic serum donors. Exposure of neonatal rat islets of Langerhans for 20 h to sera from diabetic BB rats and rabbit complement resulted in a decrease in insulin content and in insulin release upon glucose stimulation. However, the extent of islet alterations caused by sera from various BB rats was different as revealed by comparison of the ability of beta-cells to restore their functions during a 48 h recovery period. While the effect of some of the sera was completely reversible, in other cases the insulin content and/or the secretory capacity of the islets could not be fully restored indicating partially irreversible islet alterations due to pretreatment with cytotoxic BB rat serum. The potential effect of anti islet cytotoxicity in BB rat sera against autologous islets of the serum donor indicated by enhanced 51Cr-release in the presence of rabbit complement was proven in 50% (6/12) of the investigated normoglycaemic BB/OK rats. These results suggest that humoral-mediated cytotoxicity may contribute to beta-cell alteration in this model of diabetes. PMID- 2185939 TI - Radioiodination of peptide hormones and immunoglobulin preparations: comparison of the chloramine T and iodogen method. AB - Following optimization of the reaction conditions, e.g. concentration of oxidizing agents, reaction time, volume of reaction mixture, and pH, chloramine T and the new iodination reagent, Iodogen, were compared for their effectiveness in radioiodination of insulin, glucagon, human growth hormone (hGH), and rabbit anti mouse IgG. The radioactive peptide hormones prepared were analyzed for the presence of aggregate and breakdown products by polyacrylamide gel electrophoresis (PAGE) at pH 8.9, the rabbit anti-mouse IgG was tested for the presence of low molecular weight damage products by gel filtration on Sephadex G 50. The results demonstrate that with respect to iodine incorporation, specific activity, and immunological reactivity either method can be used to prepare under carefully controlled conditions a wide range of tracers with high specific activity at minimal oxidation damage. These tracers are shown to be highly suitable in radioimmunoassays after previous purification by PAGE and gel filtration, respectively. PMID- 2185940 TI - Different lymphocyte subset distribution within "insulitis" islets of normoglycaemic and prediabetic BB/OK rats of similar age. AB - The fact that insulitis occurs also in normoglycaemic BB rats led us to investigate the phenotypes of lymphocytes invading the pancreatic islets of prediabetic BB/OK rats in comparison to age- and sex-matched normoglycaemic animals in a retrospective analysis. By using a panel of monoclonal antibodies we investigated the number of pan T-cells, T-helper cells, cytotoxic T-cells and NK cells and determined the number of activated cells by measurement of class I, class II and IL-2 receptor positive cells. The bound primary antibodies were visualized using the APAAP-technique. The prediabetic rats showed a significantly decreased pancreatic insulin content which was drastically reduced at diagnosis of diabetes. This was accompanied by reduction of the B-cell volume density. The prediabetic as well as the long-term normoglycaemic BB rats showed an accumulation of mononuclear cells (all phenotypes investigated) within the pancreatic islets. Concerning the phenotypes of infiltrating cells there was no qualitative difference between long-term normoglycaemic and prediabetic rats but quantitatively an enhanced amount of W3/25+, OX-8+, OX-6+ and ART-18+ cells could be observed in the prediabetic animals. From our results we conclude that an immunological B-cell destructive process occurs also in long-term normoglycaemic BB rats by participation of mononuclear cells qualitatively not different from those observed in prediabetic animals. Activated T-cells (OX-19+, OX-8+, W3/25+) expressing class II antigens (OX-6+) and the IL-2 receptor (ART-18+) seem to play a significant role in the amplified immunological pancreatic B-cell destruction. PMID- 2185941 TI - Immortalization of macrophages from mouse bone marrow and fetal liver. AB - Fresh bone marrow (BM)-derived cells infected with the J2 recombinant retrovirus (carrying v-myc and v-raf/mil oncogenes) grow as immortal cell lines belonging to the monocytic lineage. BM cells cultured for 24 h in conventional medium are no longer able to grow following infection with the J2 virus. We investigated whether specific growth factors affected the proliferative response of BM cells to the J2 virus. If the BM cells were cultured for 24 h in the presence of concanavalin A or CSF-1 and then infected with the J2 virus, immortalization of BM cells was observed. Under these conditions, the cell lines that we obtained were shown to belong to the monocytic lineage. We investigated whether target cells for the J2 virus existed in other hematopoietic organs. We observed J2 induced proliferation in fetal liver (FL) but not in spleen or thymus. The cells proliferating in the FL had macrophage characteristics during the early passages. However, some macrophage markers were lost upon extensive in vitro culture. We conclude that we have identified conditions in which J2 virus consistently and selectively stimulates the growth of macrophages from murine bone marrow and a wider range of hematopoietic cells from fetal liver. PMID- 2185942 TI - Staurosporine induces dissolution of microfilament bundles by a protein kinase C independent pathway. AB - The protein kinase C (PKC) inhibitor staurosporine was found to dramatically alter the actin microfilament cytoskeleton of a variety of cultured cells, including PTK2 epithelial cells, Swiss 3T3 fibroblasts, and human foreskin fibroblasts. For example, PTK2 cells exposed to 20 nM staurosporine exhibited a progressive thinning and loss of cytoplasmic actin microfilament bundles over a 60-min period. During this time microtubule and intermediate filament systems remained intact (as shown by immunofluorescence and at higher resolution by photoelectron microscopy), and the cells remained spread even though microfilament bundles were absent. Higher doses of staurosporine or longer exposure times at lower doses resulted in morphological alterations, but even severely arborized cells recovered normal morphology and actin patterns after a wash and an incubation for several hours in fresh medium. The actin filament disruption induced by staurosporine was distinguishable from the actin reorganization induced by exposure to the tumor promoter (and activator of PKC) phorbol myristate acetate (PMA). Swiss 3T3 cells made deficient in PKC by prolonged exposure to PMA (PKC down-regulation) exhibited actin alterations in response to staurosporine which were comparable to those in cells which had not been exposed to the phorbol ester. In a parallel control experiment, the actin cytoskeleton of PKC-deficient 3T3 cells was unaffected in response to PMA, consistent with down-regulation of this kinase. While the exact mechanism of staurosporine-induced actin reorganization remains to be determined, the observed effects of staurosporine on PKC-deficient cells make a role for PKC unlikely. These results indicate the need for care when staurosporine is employed as an inhibitor of protein kinase C in studies involving intact cells. PMID- 2185943 TI - The dynamic distribution and quantification of DNA cruciforms in eukaryotic nuclei. AB - Cruciforms have been suggested as potential recognition structures at or near origins of DNA replication in eukaryotic cells. Monoclonal antibodies specific for cruciforms have been produced. The antibody binds to structural determinants at the base of the cruciform stem, the "elbow." Labeling of nuclei with anti cruciform antibodies produces a nonuniform pattern of fluorescence in cells arrested at the G1/S boundary. This pattern of fluorescence changes when these cells are released from synchrony. Using fluorescence flow cytometry to quantify the number of DNA cruciform structures in cells throughout the cell cycle, we observed two major populations of nuclei with different numbers of cruciforms; the modal number of cruciforms in these populations was 0.6 x 10(5) and 3 x 10(5) cruciforms per nucleus. Synchronized cells (doubly arrested by serum starvation and aphidicolin) displayed a biphasic distribution of the number of cruciforms over the first 6 h after release from synchrony with maxima at 0 and 4 h after release. PMID- 2185944 TI - Characterization of a serum-free culture system comparing growth factor requirements of transformed and untransformed cells. AB - We describe the first completely serum-free model culture system for comparing growth control in transformed and untransformed cells. Continuous maintenance of untransformed AKR-2B fibroblasts and chemically transformed AKR-MCA cells in the presence of serum-free medium containing epidermal growth factor (E), insulin (I), and transferrin (T) resulted in cell lines which proliferated with similar doubling times (14 h), comparable to parental lines maintained in 10% serum (16 h). The transformed MCA-SF cells and untransformed AKR-SF cells did not differ in their saturation densities in medium containing E + I + T. However, the monolayer proliferation of MCA-SF cells was significantly greater than that of the AKR-SF cells in the presence of E + T, I + T, or T alone. Both cell lines required T to proliferate in monolayer culture. [3H]-Thymidine incorporation experiments and autoradiographic analysis indicated that quiescent MCA-SF cells could reenter the cell cycle by addition of nutrients alone. The combination of E + I + T produced no additional stimulation of DNA synthesis. In contrast, individual polypeptide growth factors (E, I, IGF-I, PDGF, FGF a or b, or TGF-beta 1) were required to elicit a mitogenic response in the untransformed AKR-SF cells. Peak mitogenesis occurred from 18-20 h for all growth factors except TGF-beta 1 (32 h). Neither AKR-SF nor MCA-SF cells could grow with anchorage independence in serum-free medium, unless both TGF-beta 1 and FGF a or b were simultaneously present. The results indicate that this well-defined, serum-free model system can be utilized to detect growth factor-related alterations associated with the transformed state. PMID- 2185945 TI - Sensitivity of the retinal circular dichroism of bacteriorhodopsin to the mutagenetic single substitution of amino acids: tyrosine. AB - Bacteriorhodopsin (bR) in the native purple membrane, in wild type expressed in E. coli and reconstituted in lipid vesicles, and its constituted mutants with substitutions of Tyr-185 by Phe all are found to have different visible retinal CD spectra. The results strongly suggest that the environment of the retinal in bR determines the sign and heterogeneity of its visible retinal CD spectrum. This supports the recent proposal that the observed biphasic CD spectrum of bR is due to the superposition of the CD spectra having opposite signs of more than one type of bR rather than due to exciton coupling. PMID- 2185946 TI - Identification of a group of proteins that are strongly up-regulated in total epidermal keratinocytes from psoriatic skin. AB - Analysis using two-dimensional (2D) gel electrophoresis of the [35S]-methionine labelled proteins synthesized by non-cultured total epidermal keratinocytes obtained from normal and psoriatic skin revealed 6 proteins that are strongly up regulated (5 times or more) in psoriatic skin. These proteins are synthesized at albeit lower levels by keratinocytes from normal and normal-appearing (uninvolved) skin of psoriatic patients, and correspond to isoelectric focusing sample spot numbers 4311 (40.3 kDa), 4003 (12.4 kDa), 5008 (11.9 kDa), 3012 (11.6 kDa), 6016 (11.6 kDa) and 1015 (10.1 kDa) in the normal keratinocyte 2D gel protein database [Celis et al, (1990) Electrophoresis, in press]. These proteins are also detected in the labelling medium indicating that they are at least in part secreted. Given their striking regulatory behavior, these proteins may play a role in the pathogenesis of psoriasis. PMID- 2185947 TI - Stereoselective carbonyl reductases from rat skin and leukocyte microsomes converting 12-ketoeicosatetraenoic acid to 12(S)-HETE. AB - Cell-free preparations from rat polymorphonuclear leukocytes and skin were found to catalyze the reduction of 12-keto-5,8,10,14-eicosatetraenoic acid (12-KETE) to 12-hydroxyeicosatetraenoic acid (12-HETE). The reductase activity was associated with the microsomal fraction and showed a marked preference for NADH over NADPH as reducing cofactor. Characterization of the reaction product by chiral phase HPLC of the methyl ester derivative indicated that 12-KETE reduction generated almost exclusively 12(S)-HETE. The results demonstrate that rat skin and leukocyte microsomes possess an NADH-dependent 12-KETE reductase activity that forms 12(S)-HETE as a major product. The identification of stereoselective 12 KETE reductases provides a basis for further defining the role these enzymes may play in the regulation of 12-KETE levels and in the protection against degradation of 12-KETE to the pro-inflammatory 12(R)-HETE by selectively generating 12-HETE of the S configuration. PMID- 2185948 TI - Interactions of lipoyl domains with the E1p subunits of the pyruvate dehydrogenase multienzyme complex from Escherichia coli. AB - Equilibrium binding experiments were carried out with lipoyl domains and the pyruvate decarboxylase [pyruvate dehydrogenase (lipoamide), E1p, EC 1.2.4.1)] component of the pyruvate dehydrogenase multienzyme complex of Escherichia coli. The dissociation constant (Ks) was estimated to be not less than 0.3 mM, exceeding the Km value (33 microM) for reductive acetylation of the domains by an order of magnitude. Thus, the lipoyl domain, which is required to promote reductive acetylation of the lipoyl group, does not appear to do this simply by enhancing the binding to E1p. The difference between Ks and Km suggests that the formation and release of reductively acetylated lipoyl domains from the enzyme may be a relatively rapid step in the mechanism. PMID- 2185949 TI - Lack of inhibition by colicin M suggests bactoprenol independence of MDO biosynthesis. AB - Biosynthesis of membrane-derived oligosaccharides (MDO), located in the periplasmic space of Escherichia coli, was not inhibited by colicin M, an inhibitor of bactoprenyl phosphate regeneration. This result suggests that bactoprenol does not serve as a lipid carrier of MDO oligosaccharides across the cytoplasmic membrane. PMID- 2185950 TI - Cosecretion of amylin and insulin from isolated rat pancreas. AB - Amylin, a 37 amino acid C-terminal amidated peptide is an integral part of secretory granules of pancreatic beta-cells. Utilizing a specific radioimmunoassay system we demonstrate in the present study a cosecretion of amylin and insulin from the isolated rat pancreas. The secretion pattern of both peptides during glucose or glucose plus arginine stimulation is identical. The molar ratio of amylin amounts to 10% of that of insulin. The biological significance of amylin is still unknown, but a paracrine/endocrine role in glucose homeostasis is speculated. PMID- 2185951 TI - Beta-turns as structural motifs for the proteolytic processing of seed proteins. AB - Fifteen NH2- and COOH-terminal ends from both small and large chains of the most abundant 2 S albumins from Brassica napus seeds have been sequenced. This allows the determination of the exact proteolytic maturation sites of these proteins. Each one of these proteins arises from a polypeptide precursor which is cleaved during the post-translational processing at four sites, giving two different chains linked by disulphide bridges on the mature 2 S albumin. The hydrolyzed bonds involved in the processing are located in proline and glycine-rich regions, forming tetra-peptides with a very high beta-turn probability. Similar results have been found through the analysis of the 2 S albumin precursors from other seeds. These facts are interpreted in terms of the existence of a beta-turn specific endoprotease activity involved in the maturation process of 2 S albumins. PMID- 2185952 TI - Chromosomal reallocation of the chicken c-myb locus and organization of 3' proximal coding exons. AB - In the course of our studies concerning the tissue-specific expression of the c myb proto-oncogene, we have established the nucleotide sequence of the chicken c myb 3'-proximal coding exons. In situ hybridization performed with different genomic DNA probes corresponding to nearly all the c-myb gene allowed us to localize the corresponding locus on the large acrocentric chromosome 3 in chicken. Our sequencing data also indicate that the 3'-proximal noncoding sequences represented in c-myb mRNA species are derived from non-contiguous exons. PMID- 2185953 TI - Polypeptide composition of higher plant photosystem I complex. Identification of psaI, psaJ and psaK gene products. AB - High resolution gel electrophoresis of the native photosystem I complex retaining light-harvesting chlorophyll complex revealed the presence of three low-molecular mass proteins of 7, 4.1 and 3.9 kDa in spinach, and 6.8, 4.4 and 4.1 kDa in pea, in addition to the other well-characterized higher-molecular-mass components. Upon further detergent treatment to deplete light-harvesting chlorophyll complex, the 7 kDa and 4.1 kDa proteins were removed from the photosystem I core complex of spinach, while the 3.9 kDa protein was retained. N-terminal sequencing demonstrated that the 4.1 kDa proteins from both spinach and pea correspond to the gene product of ORF42/44 in chloroplast genome of liverwort and higher plants, which was previously hypothesized as a photosystem I gene (psaJ) based on sequence homology with the cyanobacterial photosystem I component of 4.1 kDa [(1989) FEBS Lett. 253, 257-263]. N-terminal sequence of the spinach 3.9 kDa and pea 4.4 kDa proteins fitted with chloroplast ORF36/40 (psaI) although no homologue has been found in cyanobacteria. The spinach 7 kDa and pea 6.8 kDa proteins correspond to the nuclear-encoded psaK product and significantly matched with the N-terminal sequence of the cyanobacterial 6.5 kDa subunit. The evolutional conservation of the psaJ and psaK seems to suggest their intrinsic role(s) in photosystem I. PMID- 2185954 TI - Osmium tetroxide, N,N,N',N'-tetramethylethylendiamine. A new probe of DNA structure in the cell. AB - It was shown that the complex of osmium tetroxide with N,N,N',N' tetramethylethylendiamine can be applied as a probe of DNA structure in the cell. This probe site-specifically recognized structural distortions at the B-Z junctions in plasmids pRW751 and pPK1 (containing (dC-dG)n segments) in E. coli cells. PMID- 2185955 TI - A novel NADPH/NADH-dependent aldehyde reduction enzyme isolated from the tapeworm Moniezia expansa. AB - An aldehyde reduction enzyme has been purified from the cytosol of the tapeworm, Moniezia expansa, by chromatofocusing and Reactive-Red chromatography. The enzyme is monomeric (subunit 34 kDa) and can utilise NADH and NADPH as co-factors. Substrates of the enzyme include alkanals, alka-2,4-dienals and alk-2-enals, established secondary products of lipid peroxidation. The enzyme reduced methylglyoxal, another possible natural substrate (M. expansa lacks glyoxalase I activity). The parasite enzyme may help form a final line of defence against cytotoxic aldehydes arising from host immune initiated lipid peroxidation. PMID- 2185956 TI - Secretion of apolipoprotein B in serum-free cultures of human hepatoma cell line, HepG2. AB - We have developed a defined medium which can maintain efficient growth of HepG2 cells sustaining the synthesis of a variety of plasma proteins including apolipoprotein B. This defined system was used to investigate long-term effects of insulin, estrogen, triiodothyronine, cholesterol, and oleate on the growth pattern of HepG2 cells and secretion rate of apolipoprotein B. Oleate and triiodothyronine caused significant increases in secretion of apolipoprotein B. The stimulatory effect of triiodothyronine was only observed after long (6 days) exposure of cells to the hormone. In contrast, insulin caused up to a 4-fold decrease in the secretion rate of apolipoprotein B during the early growth periods. This inhibitory effect appeared to be partially abolished after 6 days. Our data suggest that some important questions on regulation of apolipoprotein B expression can be addressed by the long-term culture of HepG2 cells in defined medium. PMID- 2185958 TI - Crown-rump length measurements revisited. AB - Clinical and ultrasound data of 403 first-trimester pregnancies were collected prospectively. For our CRL study, two groups of patients were selected: Group A with an optimal (menstrual) history (111 patients, 156 CRL measurements) and Group B with available BBT charts (17 patients, 27 CRL measurements). Compared to the Robinson CRL curve (SD +/- 4.7 days) the curve of group A (SD +/- 4.4 days) showed a small underestimation of gestational age of 2.5 days in the 8th week, gradually declining (p less than 0.001). The CRL curve of group B (SD 4.3 days) is parallel to the group A curve, displaced 2.9 days to the left, and did not differ significantly from the Robinson curve. IN CONCLUSION: in contrast to suggestions in literature there is no need to revise the original CRL curve of Robinson. For individual variations in CRL measurements not only measure errors but also variations in the time of implantation and/or start of growth are responsible. PMID- 2185957 TI - Eclosion hormone of the silkworm Bombyx mori. Expression in Escherichia coli and location of disulfide bonds. AB - A gene encoding eclosion hormone (EH) from the silkworm, Bombyx mori was chemically synthesized, inserted into a secretion vector and expressed in Escherichia coli, leading to the production of biologically active EH. Sequence analysis of cystine-containing peptides in a thermolysin digest of this EH established the locations of 3 disulfide bonds in the molecule. Evidence was also obtained that the 6 residues at the NH2-terminal are dispensable but 4 residues at the COOH-terminal play an important role in EH activity. PMID- 2185959 TI - The lethal multiple pterygium syndrome: prenatal ultrasonographic and postmortem findings; a case report. AB - In this report we present the prenatal ultrasonic and postmortem data of a male fetus of 25 weeks' gestational age with a lethal multiple pterygium syndrome. The importance of precise etiologic diagnosis in a midtrimester fetus with generalized edema and nuchal hygroma is emphasized. PMID- 2185960 TI - In utero diagnosis of oropharyngeal teratoma; a case report. PMID- 2185961 TI - Clinically relevant anti-epileptic drug interactions. AB - Anti-epileptic drugs frequently interact due to pharmacokinetic features (induction or inhibition of metabolism, production of active metabolites, low therapeutic indices) and the need for prolonged treatment with possible addition of other drugs to treat concomitant diseases. The most important pharmacokinetic interactions are those that inhibit phenytoin, carbamazepine and phenobarbitone metabolism and thus increase their toxicity. Drugs inhibiting metabolism include antibiotic macrolides, chloramphenicol, isoniazide, some sulphonamides, propoxyphene, cimetidine, valproic acid and sulthiame. Anti-epileptic drugs can induce hepatic microsomal enzymes and, therefore, may increase metabolism of corticosteroids, oral contraceptives, oral anticoagulants, cardiovascular agents, antibiotics, chemotherapeutic agents, psychotropic drugs and non-opiate analgesics, thereby reducing their efficacy. Advantageous pharmacodynamic interactions include synergism of ethosuximide plus valproic acid and of carbamazepine plus valproic acid. A pharmacodynamic mechanism may be responsible for the reduced sensitivity of chronically treated epileptics to some neuromuscular blockers. PMID- 2185962 TI - Pirenzepine in non-ulcer dyspepsia: a double-blind multicentre trial. AB - In a double-blind multicentre study to compare pirenzepine with placebo in non ulcer dyspepsia, 71 patients were randomized to receive 50 mg pirenzepine or placebo given orally twice daily for 4 weeks. The trial was not completed by five patients in the pirenzepine group and six in the placebo group. There were no significant differences between the groups in respect to changes in total symptoms (upper abdominal pain, nausea and vomiting, early satiety and postprandial bloating, eructation and pyrosis) scores and outcome, although 27/35 (77%) patients receiving pirenzepine were cured or improved compared with 22/36 (61%) receiving the placebo. Adverse effects were reported by 13 (37%) patients treated with pirenzepine and by six (17%) treated with placebo, seven withdrawing due to adverse effects. PMID- 2185963 TI - Non-steroidal anti-inflammatory drugs as the first step in cancer pain therapy: double-blind, within-patient study comparing nine drugs. AB - The efficacy and tolerability of acetylsalicylic acid, paracetamol, diclofenac, ibuprofen, indomethacin, pirprofen, sulindac, naproxen and suprofen were compared in the treatment of cancer pain. In a double-blind, within-patient randomized study, each drug was given for 1 week to eight patients and for another week to a further eight patients. A total of 65 patients were effectively treated; only 48 completed week 1 and 41 completed week 2. Naproxen, diclofenac and indomethacin were highly effective in pain relief (tested by means of a 100 mm visual analogue scale) and were relatively well tolerated. It is concluded that these non steroidal anti-inflammatory drugs can be considered as first choice in the treatment of cancer pain. PMID- 2185964 TI - Recurrent respiratory infections in childhood: experience with a bacterial extract plus bacterial ribosomes (Immucytal). AB - A total of 60 children (mean age +/- SD 7.6 +/- 3.5 years, range 2 - 14.2 years) with recurrent respiratory infections were treated with bacterial wall extract plus bacterial ribosomes (Immucytal) or placebo sprayed into the nostrils and oropharynx three times a day for 1 or 2-week periods over 3.5 months. The treatment was completed by 58 subjects; two patients in the placebo-treated group were withdrawn, one for poor compliance and the other because of headaches. Respiratory symptoms improved from the first month in the Immucytal treated children, but not in the placebo group, with a reduction in the incidence of infections in the upper and lower airways. No changes were noted in respiratory function parameters. Treatment with Immucytal significantly increased serum immunoglobulin A (P less than 0.02) and immunoglobulin M (P less than 0.01) and enhanced skin response to the in vivo lymphocyte blastization test, but there was no significant change in the circulating lymphocyte subpopulations. Both physicians and the patients' parents judged the bacterial extract to be clinically better than the placebo. Immucytal, therefore, may provide a useful alternative therapy for recurrent respiratory infections in infancy. PMID- 2185965 TI - Effect of fenticonazole spray in cutaneous mycosis: a double-blind clinical trial versus cyclopyroxolamine spray. AB - A double-blind clinical trial was performed to evaluate efficacy and tolerance of once-daily 2% fenticonazole compared with 1% cyclopyroxolamine spray applied for 2-4 weeks in 100 patients with cutaneous mycotic lesions. After treatment lasting 21.9 +/- 6.7 or 22.5 +/- 6.2 days, respectively, patients receiving fenticonazole or cyclopyroxolamine had negative microscopic findings and cultures were sterile. Comparable clinical improvement was observed in both treatment groups, with 91.8% and 89.8% of patients, respectively, receiving fenticonazole or cyclopyroxolamine being evaluated as cured or greatly improved. Following a drug-free period, the clinical evaluation of nine (20.9%) patients treated with fenticonazole and 14 (30.4%) treated with cyclopyroxolamine worsened. The incidence of side-effects was low; only one patient withdrew from treatment because of a slight itch. It is suggested that fenticonazole and cyclopyroxolamine are equally effective in eradicating cutaneous mycoses and that their efficacy and tolerance are comparable. PMID- 2185966 TI - Long-term treatment with the somatostatin analogue SMS 201-995: alternative to pancreatectomy in persistent hyperinsulinaemic hypoglycaemia of infancy. AB - Nine patients with persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI), aged 3 days to 11 months, received octreotide therapy at a dose of 5-10 micrograms s.c. every 4-8 h according to glucose response. The response to octreotide was variable and unpredictable. Two patients could not be weaned off intravenous glucose and 2 others could be weaned off but required continuous nasogastric feedings. In the remaining 5 patients relatively normal feeding schedules were instituted. Long-term ambulatory treatment is an attractive alternative to surgery in such patients if the family can cope with the injections and dietary regimens. Although octreotide suppresses growth hormone secretion, all patients continue to grow during octreotide treatment. PMID- 2185967 TI - A study of octreotide in oesophageal varices. AB - A comparison of octreotide infusion (25 micrograms/h) and placebo in 16 stable cirrhotic patients revealed a 30% reduction in transhepatic venous gradient between 0 and 60 min in the octreotide group without an effect on systemic haemodynamics. In a separate trial, 40 patients with active variceal bleeding were randomized to octreotide infusion (25 micrograms/h for 48 h) or oesophageal tamponade. The 2 treatments gave comparable control of variceal bleeding. Tolerance of treatment was significantly better in the octreotide group. In summary, octreotide infusion is simple to administer, has few side effects, and may be of use in the immediate control of oesophageal bleeding. PMID- 2185968 TI - Octreotide and gastrointestinal fistulae. AB - The place of somatostatin and its analogues in the management of gastrointestinal fistulae is reviewed, drawing attention to the difficulty of assessing treatments that influence spontaneous closure. Sixteen patients with gastric, small bowel, and pancreatic fistulae were randomized to receive octreotide injections (100 micrograms t.i.d.) or placebo for 12 days. Spontaneous fistula closure occurred in 7 at a mean of 37 days after entering the trial. A second study is underway with greater patient numbers recruited from peripheral hospitals and with an increased period of octreotide medication (21 days). PMID- 2185969 TI - Pancreatic exocrine and gallbladder function during long-term treatment with octreotide (SMS 201-995). AB - Since octreotide (SMS 201-995, Sandostatin; Sandoz Pharmaceuticals) is a potent inhibitor of pancreatic exocrine secretion and gallbladder contraction, long-term treatment with this drug may theoretically result in impaired pancreatic function and gallstones. However, we observed excellent pancreatic exocrine function--as assessed by the PABA/PAS test--in acromegalics who received octreotide treatment for more than 6 months. Plasma cholecystokinin showed a significant, although blunted, postprandial response, which exceeded the threshold for gallbladder contraction in healthy controls. Remarkably, postprandial gallbladder contraction was completely abolished for at least 2 h during octreotide treatment. In contrast to other studies, none of 16 acromegalic patients on long-term octreotide treatment developed gallstones. Although the incidence of gallstones in patients on long-term octreotide treatment may be increased, the risk seems to be variable. PMID- 2185970 TI - Dihydrofolate reductase as a therapeutic target. AB - The folate antagonists are an important class of therapeutic compounds, as evidenced by their use as antiinfective, antineoplastic, and antiinflammatory drugs. Thus far, all of the clinically useful drugs of this class have been inhibitors of dihydrofolate reductase (DHFR), a key enzyme in the synthesis of thymidylate, and therefore, of DNA. The basis of the antiinfective selectivity of these compounds is clear; the antifolates trimethoprim and pyrimethamine are potent inhibitors of bacterial and protozoal DHFRs, respectively, but are only weak inhibitors of mammalian DHFRs. These species-selective agents apparently exploit the differences in the active site regions of the parasite and host enzymes. Methotrexate is the DHFR inhibitor used most often in a clinical setting as an anticancer drug and as an antiinflammatory and immunosuppressive agent. Considerable progress has been made recently in understanding the biochemical basis for the selectivity of this drug and the biochemical mechanism (or mechanisms) responsible for the development of resistance to treatment with the drug. This understanding has led to a new generation of DHFR inhibitors that are now in clinical trials. PMID- 2185972 TI - Biochemistry of fish antifreeze proteins. AB - Four distinct macromolecular antifreezes have been isolated and characterized from different marine fish. These include the glycoprotein antifreezes (Mr 2.5-33 K), which are made up of a repeating tripeptide (Ala-Ala-Thr)n with a disaccharide attached to the threonyl residues, and three antifreeze protein (AFP) types. Type I is an alanine-rich, amphiphilic, alpha-helix (Mr 3-5 K); type II is a larger protein (Mr 14 K) with a high content of reverse turns and five disulfide bridges; and type III is intermediate in size (Mr 6-7 K) with no distinguishing features of secondary structure or amino acid composition. Despite their marked structural differences, all four antifreeze types appear to function in the same way by binding to the prism faces of ice crystals and inhibiting growth along the a-axes. It is suggested that type I AFP binds preferentially to the prism faces as a result of interactions between the helix macrodipole and the dipoles on the water molecules in the ice lattice. Binding is stabilized by hydrogen bonding, and the amphiphilic character of the helix results in the hydrophobic phase of the helix being exposed to the solvent. When the solution temperature is lowered further, ice crystal growth occurs primarily on the uncoated, unordered basal plane resulting in bipyramidal-shaped crystals. The structural features of type I AFP that could contribute to this mechanism of action are reviewed. Current challenges lie in solving the other antifreeze structures and interpreting them in light of what appears to be a common mechanism of action. PMID- 2185971 TI - Mechanisms of cytochrome P-450 catalysis. AB - Cytochrome P-450 (P-450) enzymes catalyze the oxidation of a wide variety of substrates. Although a large number of P-450s have been characterized in different species and tissues, the mechanisms of catalysis of oxygenation may be understood in terms of a few basic principles. The chemistry is dominated by the ability of a high-valent formal (FeO)3+ species to carry out one-electron oxidations through the abstraction of hydrogen atoms, abstraction of electrons in n or pi orbitals, or the addition to pi bonds. A series of radical recombination reactions then completes the oxidation process. The protein structures are postulated to provide the axial thiolate ligand to the heme, to control the juxtaposition of the substrate (and therefore the regio- and stereoselectivity of oxidation), to alter the effective oxidation potential of the (FeO)3+ complex, and possibly to participate in specific acid/base catalysis in the oxidation of some substrates. PMID- 2185973 TI - Mechanisms responsible for the cardiotoxic effects of cocaine. AB - Cocaine can induce lethal cardiovascular events, including myocardial infarction and ventricular fibrillation. The mechanisms responsible for these cardiotoxic effects of cocaine remain largely to be determined. Cocaine has both sympathomimetic (inhibition of neuronal uptake of norepinephrine) and local anesthetic (Na+ channel blockade) properties. Neurotransmitters released from cardiac sympathetic nerves bind to both alpha- and beta-adrenergic receptors eliciting a cascade of intracellular responses. Stimulation of beta-adrenergic receptors activates adenylate cyclase, increasing cyclic AMP levels, whereas alpha-adrenergic receptor stimulation activates phospholipase C, increasing inositol trisphosphate. These second messengers, in turn, elicit increases in cystolic calcium. Elevations in cystolic calcium can provoke oscillatory depolarizations of the cardiac membrane, triggering sustained action potential generation and extrasystoles. Cocaine also acts as a local anesthetic by inhibiting sodium influx into cardiac cells, which impairs impulse conduction and creates an ideal substrate for reentrant circuits. Thus, the adrenergic and anesthetic properties of cocaine could act synergistically to elicit and maintain ventricular fibrillation. Adrenergic receptor activation would trigger the event whereas sodium channel blockade would create the reentrant substrate to perpetuate the malignant arrhythmias. PMID- 2185974 TI - Molecular genetics of neuronal development in the Drosophila embryo. AB - Making a functional nervous system involves the production of specific types of neurons in characteristic locations and their ability to find and synapse with appropriate target cells. By capitalizing on the advanced genetics and molecular biology of Drosophila, a rapidly growing number of genes have been identified that control these events. Studies of the expression and function of these genes in single, uniquely identified cells is possible because of the relative simplicity of the Drosophila embryonic nervous system. A class of neurogenic genes, including N, Dl, and E(spl), controls the emergence of the entire neuronal precursor population, whereas some of the segmentation genes, such as ftz and eve, control the fates of individual neurons. Later in development, genes encoding cell-surface molecules, called fasciclins, may be involved in the ability of growing neurons to recognize and elongate axons along specific pathways to reach their synaptic targets. PMID- 2185975 TI - Recent developments in the field of iron-sulfur proteins. AB - This review considers recent information, in the following order, on complex proteins containing Fe-S clusters together with other prosthetic groups, on hydrogenases, unexpected functions of Fe-S clusters, novel cluster types, protein structures furnishing the cluster ligands, evolutionary aspects, and spectroscopic methods and theoretical approaches used or developed in the study of Fe-S proteins. PMID- 2185976 TI - Quantification of gastric ulcer healing by endoscopic ultrasonography. AB - We studied and quantified the healing process of gastric ulcers in humans by means of endoscopic ultrasonography. Initially, using the water bath method, we scanned specimens of resected human stomachs with gastric ulcers including 9 open ulcers and 14 ulcer scars. Comparison of histological findings and measurement of the cross-section suggested that the ulcers observed in the ultrasonographic photographs were essentially equivalent to those in histological photographs. By using endoscopic ultrasonography, we then examined 16 patients with active, mainly recurrent, gastric ulcers before and after 2, 4, and 8 weeks of H2 blocker treatment, measuring the length and cross-sectional area of the ulcer in endoscopic ultrasonographic photographs. From measurements of the contraction rate of cross-sectional ulcer area during healing, we observed that the healed ulcers showed a relatively rapid rate of contraction in the first 4 weeks of therapy and the non-healed cases showed a poor contraction rate. Endoscopic ultrasonography is useful for the quantitative estimation of histological changes associated with gastric ulcer healing. PMID- 2185977 TI - A comparative evaluation of sclerosants for esophageal varices: a prospective randomized controlled study. AB - The aim of this prospective randomized controlled study was to find a safe and effective sclerosing solution for endoscopic injection sclerotherapy in the treatment of esophageal variceal bleeding. Ninety consecutive patients with portal hypertension and variceal bleeding were randomized to receive sclerotherapy with 5% ethanolamine oleate, 3% sodium tetradecyl sulfate, or absolute alcohol at an interval of 3 weeks. Sixty-four patients who received more than three sessions were analyzed. All three agents were found to have similar success and complication rates (p greater than 0.05). However, absolute alcohol required fewer sessions (p less than 0.01) and lesser amounts (p less than 0.01) to produce successful variceal sclerosis and had the added advantage of low cost and easy availability. PMID- 2185979 TI - Tube migration in PEG. PMID- 2185978 TI - The evolution of diagnostic ERCP. PMID- 2185980 TI - In vitro fertilization in Kock's ileostomy patients. Prior evaluation by pelvic ultrasonography. AB - The study describes Kock's continent ileostomy in 2 females, both of whom were suffering from tubal infertility. Appropriate placement of the abdominal pouch, permitting in vitro fertilization embryo transfer treatment, was present in 1 patient. In the other patient, an ultrasonographic examination demonstrated the pouch covering the entire surface area of both ovaries. Oocyte aspiration was thus precluded for fear of penetrating the pouch. Ovum pickup in the presence of a Kock continent ileostomy can be conducted safely and without risk, if the pouch is correctly positioned above the small pelvis. Ultrasonography facilitated the ability to locate the patients' ovaries and precise position of the pouch. PMID- 2185981 TI - Turner's syndrome--review of the literature with reference to a successful pregnancy outcome. AB - A 30-year-old Japanese female with Turner's syndrome had become pregnant and delivered a normal male infant by cesarean section. Her menarche was at age 14, and secondary sex characteristics developed normally. She had some features of Turner's syndrome, and cytogenetic studies from peripheral blood lymphocytes and several tissues revealed only 45,XO karyotype without evidence of mosaicism. To our knowledge, she is only the thirteenth case of monosomy X to achieve pregnancy. A review of the literature indicates a high incidence of fetal wastage and increased chromosomal errors in the offspring of women with a 45,XO cell line with or without mosaicism. PMID- 2185982 TI - Medicare payment appeals process is slow. PMID- 2185983 TI - The ongoing capital pass-through battle: is a solution in sight? AB - The debate over whether and how to incorporate Medicare Part A capital payments into the prospective pricing system is beginning to seem like a political rerun, as the Health Care Financing Administration prepares its third proposed capital regulations. And once again hospitals are sprucing up opposing arguments to convince Congress that they are right and HCFA is wrong. PMID- 2185984 TI - Characterization of a bovine leucocyte differentiation antigen of 145,000 MW restricted to B lymphocytes. AB - A new bovine B-cell differentiation antigen is described that is detected by three monoclonal antibodies (mAb). The antigen is not an immunoglobulin and is precipitated from peripheral B cells as a molecule with an approximate molecular weight (MW) of 120,000 or 145,000 before and after reduction, respectively. Data obtained from two-colour cytofluorimetry and immunohistochemistry confirmed that the antigen was found only on mature B cells and on cells with dendritic morphology in the follicles of the organized lymphoid tissues. Its level of expression is directly correlated with that of IgM on peripheral blood B cells and Theileria parva-transformed B cells. The marker was also expressed on the peripheral cells which expressed surface IgG. Based on the antigen's cellular distribution, biochemistry and histochemistry, it is considered to be analogous to the human CD21 antigen. PMID- 2185985 TI - IL-1 transcriptionally activates the neutrophil chemotactic factor/IL-8 gene in endothelial cells. AB - Leucocytes and vascular cells interact closely in inflammation and immunity and cytokines are important mediators of this interaction. The present study was designed to define the capacity of human endothelial cells (HEC) to produce a monocyte-derived neutrophil chemotactic factor (provisionally termed IL-8). IL-8 is a polypeptide chemotactic for neutrophils originally identified in the culture supernatant of lipopolysaccharide (LPS)-stimulated monocytes. IL-1 induced high levels of production of neutrophil chemotactic activity in culture supernatants of HEC. Optimal stimulation of activity was observed when HEC were cultured with 10-100 ng/ml IL-1 beta for 16 hr. Anti-IL-8 antibody blocked the chemotactic activity for neutrophils of IL-1-activated HEC supernatants. IL-1-treated HEC expressed high levels of IL-8 mRNA transcripts, as assessed by Northern blot analysis. Tumour necrosis factor (TNF) and LPS, unlike the inflammatory monokine IL-6, also induced IL-8 expression. Nuclear run-off experiments revealed that IL 1 activated transcription of the IL-8 gene. The production of IL-8 may represent a mechanism whereby endothelial cells, exposed to inflammatory signals, participate in the regulation of neutrophil extravasation. PMID- 2185987 TI - Functional anatomy of the larynx. PMID- 2185986 TI - Activation of monocytic cells by monoclonal antibodies to the CD11a/18 (LFA-1) complex: mediation by Fc receptor. AB - IgG1 antibodies reacting with several monocytic antigens form a bridge between the specific antigen and the Fc receptors also expressed on these cells. This results in calcium mobilization and generation of superoxide. Single IgG1 antibodies reacting with the CD11a/CD18 cellular adhesion molecular complex do not, however, induce monocytic activation. This is not because they induce a negative signal, as the response to formyl-methionyl-leucyl2-phenylalanine (FMLP) or direct cross-linking of FcRII is not inhibited. Furthermore, a combination of an intact CD11a and CD18 antibody does induce a rise in intracellular calcium and production of superoxide. This activation is dependent on the binding of the Fc portion of both antibodies to Fc receptors, as F(ab')2 fragments do not cause activation. This suggests that simultaneous binding of opsonized bacteria to cellular adhesion molecules and to Fc receptors on monocytes would facilitate activation of these cells. Furthermore, it illustrates the importance of using F(ab')2 fragments in the analysis of signal transduction molecules on Fc receptor bearing cells. PMID- 2185988 TI - Anesthesia and the "problem upper airway". PMID- 2185989 TI - Invasive methods for securing an airway. PMID- 2185990 TI - Anesthesia for laser surgery. PMID- 2185991 TI - Ocular drugs and anesthesia. PMID- 2185992 TI - Considerations for pediatric eye surgery. PMID- 2185993 TI - Muscle relaxants and the open globe. PMID- 2185994 TI - Anesthetic considerations in otolaryngological and ophthalmological outpatient surgery. PMID- 2185995 TI - Detection of antibodies to human T-lymphotropic virus type I by using synthetic peptides. AB - We describe an enzyme-linked immunosorbent assay (ELISA) for antibodies to HTLV-I using synthetic peptides corresponding to antigenic regions of HTLV-I structural protein. We observed that the peptides amino acid 100-119, 100-130, 131-160 and 295-314 of the gag protein, and 89-115, 175-199, 350-386 and 458-488 on the env protein correspond to the antigenic regions of HTLV-I structural protein. In particular, the peptide corresponding to amino acid 100-130 of the gag protein reacted with antibodies in all sera from HTLV-I carriers diagnosed by particle agglutination assay (PA) and indirect immunofluorescence assay (IF), but did not react with sera from healthy volunteers judged to be negative by PA and IF. Our results indicate that the ELISA using the peptide 100-130 of the gag protein can be used for donor screening of HTLV-I antibodies. PMID- 2185997 TI - The investigation and diagnosis of tricuspid atresia. PMID- 2185996 TI - Transmission of HTLV-I to rabbits via semen and breast milk from seropositive healthy persons. AB - Four rabbits inoculated intravenously with milk cells from 4 post-partum women seropositive for human T-cell leukemia virus type I (HTLV-I) and one rabbit inoculated with semen cells from a seropositive healthy man seroconverted for HTLV-I after 3-5 weeks but no seroconversion occurred in 2 rabbits inoculated with milk cells from a seronegative mother or with heated (56 degrees C, 30 min) milk cells from a seropositive mother. Attempts were made to isolate HTLV-I from peripheral blood lymphocytes harvested 5-15 weeks after cell inoculation and cultured in the presence of interleukin-2. An HTLV-I-carrying lymphoid cell line of rabbit origin was established from a rabbit inoculated with milk cells. Another long-term culture, derived from a rabbit inoculated with semen cells, also expressed HTLV-I antigens and harbored virus particles. Furthermore, transfusion of 20 ml of blood from all 5 seroconverted rabbits, but not from the 2 seronegative ones, caused seroconversion in normal recipient rabbits after 4-6 weeks. PMID- 2185998 TI - Doppler evaluation of superior caval venous pathways after Mustard and Senning operations. AB - Doppler waveforms from the superior caval vein were analysed to evaluate the patency of superior caval venous pathways following venous redirection (Mustard and Senning) operations for complete transposition. The group consisted of 26 unselected survivors of Mustard (9 patients) and Senning operations (17 patients). Patients were examined a mean of 5.9 (range 0.1-15.3) years following operation and their age at study ranged from 0.4-25.3 years, mean 7.3 years. Doppler waveforms were correlated with digital subtraction angiograms, which were performed in every patient within 24 hours of the Doppler study. Totally occluded superior caval venous pathways were identified in 3 patients with digital subtraction angiography. The remaining patients had angiographically patent pathways. In the 23 patients with patent pathways, Doppler waveforms demonstrated an initial systolic peak smaller than a second diastolic peak. In the 3 patients with totally occluded pathways, the pattern of the waveform was reversed, with the systolic larger than the diastolic peak. Doppler examination of the superior caval vein is a quick and simple bedside method of accurately determining patency of superior caval venous pathways after atrial redirection procedures for complete transposition. PMID- 2185999 TI - HTLV-I. PMID- 2186000 TI - Ocular changes in leprosy. PMID- 2186001 TI - Topical tretinoin in the treatment of photodamaged skin. Current status and future prospects. PMID- 2186002 TI - The elongated dermal papillae of psoriasis. Dermatome shaving, cautery, laser, pressure, tape, cryotherapy. PMID- 2186003 TI - Penicillamine-induced pemphigus erythematosus. AB - Pemphigus erythematosus occurred in a patient with rheumatoid arthritis who was treated with D-penicillamine. The skin lesions appeared 4 months after the onset of D-penicillamine treatment and persisted 14 years after cessation of this drug. Topical betamethasone dipropionate applications resulted in complete regression of the cutaneous lesions. PMID- 2186004 TI - Bullous hemorrhagic primary systemic amyloidosis. PMID- 2186005 TI - Lichen pigmentosus with scarring alopecia and circulating antinuclear antibodies. PMID- 2186006 TI - The history of nursing research in Finland. PMID- 2186007 TI - Is there a common definition for invasiveness? Report from an informal workshop on Interdisciplinary Aspects of Invasiveness, March 9-11, 1989, Neggio/Lugano, Switzerland. PMID- 2186008 TI - The discrimination of similarly colored objects in computer images of the ocular fundus. AB - The STARE (STructured Analysis of the REtina) project uses object-identification and artificial intelligence techniques to provide automated diagnoses from color pictures and fluorescein angiograms of the ocular fundus, or automated change detection from sequential images. As part of the object-identification process, we apply expert judgment and experimentation to define features--such as size, shape, color, and texture--of objects (disk, blood vessels, lesions) in digitized images. In our initial investigations, we explored color alone, because it yields a great deal of information in the classification process. We verified that even similarly colored lesions (exudates, cotton-wool spots, and drusen) could be classified by color with moderate success by a quadratic discriminant function. When color alone is not sufficient, refinement in the classification of objects may be achieved by using more features in statistical pattern recognition. Ultimately, we build a description of the fundus image which can be used either to identify one or more diagnoses that can cause the pattern of lesions in the ocular fundus or to recognize change in sequential images. PMID- 2186009 TI - Apraclonidine effects on ocular responses to YAG laser irradiation to the rabbit iris. AB - Apraclonidine (p-aminoclonidine) ophthalmic solution effectively reduces the rise in intraocular pressure (IOP) following anterior segment laser surgery. We tested the effect of topical 0.5% apraclonidine on intraocular pressure and on protein and prostaglandin (PG) E2 concentrations in aqueous humor following Q-switched Nd:YAG laser irradiation to the iris of albino rabbits, at an energy level of 2 to 200 mJ. IOP was measured prior to and for 24 hr after irradiation. Aqueous humor was withdrawn before and 1 hr after laser irradiation for determining protein (Lowry method) and PGE2 (radioimmunoassay). Four to seven rabbits were used for each experiment. The increase in IOP and protein concentration following laser irradiation was demonstrated to be dependent on the amount of laser energy. Apraclonidine completely abolished the IOP rise, and significantly reduced the elevation of protein content. Apraclonidine failed to affect the increase in PGE2. PMID- 2186010 TI - Effects of age and rapid high-pressure fixation on the morphology of Schlemm's canal. AB - An analysis of size, shape, vacuole and cell counts of Schlemm's canal was undertaken in 20 human eyes that had undergone conventional immersion fixation. A reduction in vacuole count with age was shown to be associated with a decreased canal cell count. The decrease in cell count with age was closely linked to an age-related reduction in the size of Schlemm's canal, notably a reduction in meridional width of the canal. An additional 18 human eyes underwent rapid perfusion fixation at 29.5 mm Hg to investigate the age-related response in the number of giant vacuoles present to this change in environment. A 4-fold increase in vacuole count compared to controls was demonstrable, but the numbers declined with age and the decline was closely correlated with a parallel reduction in cell numbers with age. It was possible to show that the reduction in cell and vacuole counts with age in the perfused eyes could be fully explained by the reduction in canal size: the numbers of vacuoles produced per cell and the vacuoles and cells per unit width of canal did not vary with age. It was also of interest that the pressure-related increase in vacuole numbers probably occurred within 15 min, which implies that in vivo the canal endothelium can respond quickly to changes in intraocular pressure. PMID- 2186011 TI - Growth factor responsiveness of human retinal pigment epithelial cells. AB - Growth factor effects on DNA synthesis in density-arrested human retinal pigment epithelial cells were assessed by [3H]-thymidine incorporation. Acidic and basic fibroblast growth factor and epidermal growth factor were potent stimulators, whereas platelet-derived growth factor, insulinlike growth factor-1, and insulin were weak or modest stimulators when used alone. When used in combination, each of the above growth factors caused a significant enhancement of [3H]-thymidine incorporation regardless of its effect when used alone. The combination of all four growth factors was significantly more effective than all other combinations, demonstrating synergism in their action. Similar results were found in cell proliferation assays. In contrast to this, transforming growth factor-beta inhibited the ability of each of the other growth factors and serum-containing media to stimulate [3H]-thymidine incorporation. These data suggest that DNA synthesis in human retinal pigment epithelial cells can be modulated by several growth factors, some in a stimulatory or synergistic manner and at least one in an inhibitory manner. A better understanding of these complex interactions may provide insights relevant to normal and abnormal ocular wound healing. PMID- 2186012 TI - Identification of an adhesion-associated protein of the retinal pigment epithelium. AB - The normal function of the retinal pigment epithelium (RPE) is dependent on the maintenance of tight adhesions between cells. In order to identify cell surface molecules which may be important for maintaining the integrity of the RPE, we have undertaken a combined functional, biochemical, and immunohistochemical analysis of cell surface proteins of the RPE. These studies have led to the identification of a 100-kD cell surface protein whose presence correlates with the maintenance of calcium-dependent adhesions between RPE cells. In intact RPE tissue the protein is concentrated at the junctions between RPE cells. The properties of the protein suggest that it may be a member of the cadherin family of calcium-dependent cell adhesion proteins. PMID- 2186014 TI - Lumbar puncture headache: a review. AB - August Bier, the father of spinal anesthesia, suffered and reported the first lumbar puncture (LP) headache. On August 24, 1898 his assistant, a Dr. Hildebrandt, attempted to administer a spinal anesthetic to Dr. Bier; it was never completed because the syringe did not fit the already implanted spinal needle. Bier himself suggested that continued leakage of cerebrospinal fluid (CSF) through the dural puncture site was the cause of headache, a theory that has been embraced by the medical community; however, the mechanism is probably more complex. Nearly 50 years ago, J. Lawrence Pool, using an endoscopic technique to visualize the surface of the spinal cord and the cauda equina, frequently observed large collections of epidural fluid two to four days following lumbar puncture in patients without headache. Evidence that will be presented below suggests that CSF volume alterations may be the signal closest to the headache mechanism. PMID- 2186013 TI - Cytoskeletal redifferentiation of feline, monkey, and human RPE cells in culture. AB - Retinal pigment epithelial (RPE) cells in vivo have a polarized structure with specialized apical and basal faces. Isolated RPE cells lose but eventually regain their epithelial morphology under appropriate culture conditions. We evaluated the ability of isolated feline, primate, and human RPE cells to regain this morphology in culture with scanning electron, transmission electron, phase contrast, and immunofluorescence microscopy. In culture, isolated RPE cells lose their cuboidal shape, their apical microvilli, and their in vivo cytoskeletal organization. Stress fibers from in these cells; microtubules radiate from the cells' center to their periphery; and vimentin filaments radiate from the cells' nucleus to their periphery. As cultures become confluent, RPE cells aggregate into small groups, gradually regaining a cuboidal shape and acquiring microvilli on their apical surface. Filamentous actin redistributes to the apical face where it presumably forms the cytoskeletal core normally present in RPE microvilli. Stress fibers disappear and are replaced by a circumferential microfilament bundle (CMB). Confluent cells surrounding the colonies of differentiated RPE attain a cuboidal shape but do not show complete cytoskeletal redifferentiation. Such cells, while appearing to be differentiated by phase contrast microscopy, fail to develop a compacted CMB. In these cells, f-actin is organized as a loose peripheral band within the cell cytoplasm. Our observations indicate that confluency cannot be equated with the end stage of morphologic differentiation, and that cytoskeletal organization provides a more accurate gauge of RPE maturation in culture. PMID- 2186015 TI - Transcranial Doppler evaluation of common and classic migraine. Part I. Ultrasonic features during the headache-free period. AB - To study vascular abnormalities in migraine, transcranial Doppler (TCD) was used for evaluation of 100 consecutive patients with either common or classic migraine during the headache-free period. We insonated the basal cerebral arteries and the internal carotid artery (ICA) in the neck. Particular ultrasonic features in migraineurs included intracranial elevations of mean flow velocity (MFV) above 3 standard deviations of normal values in 16%, probably reflecting increased vasotonus. Marked asymmetry of MFV in corresponding intracranial arteries was found in 12%, and could represent "asymmetrical" vascular tone. Characteristic vascular bruits of low frequency and sometimes harmonic quality were detected in 56%. When compared to TCD findings in 40 young controls, MFV were significantly higher in all intracranial arteries in migraineurs, but not in the cervical ICA. Marked differences were also found for incidence of MFV elevations and vascular bruits (p less than 0.0001). Vascular reactivity in response to eye closing as measured by flow changes in the posterior cerebral artery (visually evoked flow) was significantly greater in migraineurs than in controls (%MFV change, 14.1 +/- 5.4 vs 11.4 +/- 4.8; p = 0.004). TCD features did not discriminate common from classic migraine. Taken together, our results support the view of intracranial vascular abnormality in migraineurs reflecting, in particular, a narrower and more reactive arterial tree. The value of TCD in the differential diagnosis of "vascular headache" and in the study of migraine pathophysiology will have to be determined in the future. PMID- 2186016 TI - Transcranial Doppler evaluation of common and classic migraine. Part II. Ultrasonic features during attacks. AB - Transcranial Doppler (TCD) examinations were performed in 13 patients with common and 5 patients with classic migraine during attacks and compared to TCD findings during the headache-free period. Two distinct patterns of flow changes were detected to distinguish common from classic migraine on the basis of TCD findings. During attacks, patients with common migraine exhibited reduction of flow velocities associated with an increase of pulse wave amplitudes. Vascular bruits that were heard during the headache-free interval often disappeared. Opposite changes were found in attacks of classic migraine during the headache phase with increase of flow velocities, decrease of pulsatility and more prominent or newly appearing bruits. These findings were often diffuse and did not appear to correlate with side of headache or side of neurological aura. Uniform changes occurred in the cervical internal carotid artery and the basal cerebral arteries in either form of migraine. We propose that these changes represent caliber fluctuations of the large arteries, suggesting vasodilatation during attacks of common migraine and vasoconstriction during attacks of classic migraine. We do not intend to imply a casual role of these preliminary findings in migraine pathogenesis, but we suggest that TCD be used in combination with other methods to study vascular changes in migrainous disorders. PMID- 2186018 TI - Check your references or rediscovering the wheel. PMID- 2186017 TI - Balancing the right to habilitation with the right to personal liberties: the rights of people with developmental disabilities to eat too many doughnuts and take a nap. AB - In the pursuit of efficient habilitation, many service providers exercise a great deal of control over the lives of clients with developmental disabilities. For example, service providers often choose the client's habilitative goals, determine the daily schedule, and regulate access to preferred activities. This paper examines the advantages and disadvantages of allowing clients to exercise personal liberties, such as the right to choose and refuse daily activities. On one hand, poor choices on the part of the client could hinder habilitation. On the other hand, moral and legal issues arise when the client's right to choice is abridged. Recommendations are offered to protect both the right to habilitation and the freedom to choose. PMID- 2186019 TI - Geriatric psychiatry: an update. AB - During the past decade geriatric psychiatry has progressed from syndrome identification at a general level to the more sophisticated typological studies of the etiology, diagnosis, course, and pharmacologic treatment of illnesses such as Alzheimer's disease, depression, depression in dementia, and geriatric mania. The authors review recent findings of studies of these disease states. PMID- 2186021 TI - High anxiety in children. AB - Although reliable biological markers of dysfunctional childhood anxiety disorders are lacking, such disorders can be recognized by their symptoms. In separation anxiety and avoidance disorders, anxiety is limited to certain settings; in overanxious disorder, anxiety is generalized. Treatment for childhood anxiety disorders has included behavioral and pharmacologic intervention alone or in combination, but evidence of the efficacy of medical treatment is sparse. Some antidepressants and benzodiazepines have undergone limited studies. Clonazepam has been chosen for further study because in adults it reduced panic attacks and produced few serious side effects. In extensive studies of clonazepam for childhood seizure disorders, side effects were reported, but later reports indicate that many side effects were due to rapid induction and large doses. Transient drowsiness, lethargy, irritability, or excitability have been reported in various epilepsy studies. Clonazepam's minimal potential for drug interactions is another feature recommending it for extended trials in childhood anxiety disorders, and such a double-blind crossover study is underway. PMID- 2186020 TI - Clonazepam and imipramine in the treatment of panic attacks: a double-blind comparison of efficacy and side effects. AB - Data from 12 patients (in two control study groups) provide preliminary results of an ongoing double-blind comparison of clonazepam and imipramine in the treatment of panic disorder. In both treatment groups, the patients' global improvement was substantial over the first few weeks and persisted over the 6 month treatment period based on assessments by the therapist and the patient; side effects were mild. Faintness was slightly more prevalent among patients on clonazepam treatment but disappeared after the first few weeks. Mild, persistent tachycardia was reported among patients receiving imipramine. No tolerance emerged, and discontinuation was successful in 2 patients from each group after 6 months of treatment. Eight patients needed continued medication (25-50 mg/day of imipramine, 0.5-2.0 mg/day of clonazepam) to maintain substantial improvement. Findings confirm earlier reports from open studies that low doses of both drugs eliminate panic attacks (about 50 mg/day for imipramine and 1.5 mg/day for clonazepam). PMID- 2186022 TI - Chest pain, cardiac disease, and panic disorder. AB - Chest pain is one of the most frequent symptoms prompting presentation to a medical clinic. In primary care, more than 80% of patients are found to have no organic etiology for chest pain. Even among selected patients referred for coronary arteriography, 10% to 30% have little or no evidence of coronary artery disease. Recent studies suggest that panic disorder is a common cause of chest pain in patients with negative cardiac test results. Panic disorder can also occur along with a chronic medical illness, such as coronary artery disease, and may lead to physiologic worsening of that illness with more frequent episodes of chest pain. PMID- 2186023 TI - Clonazepam in the treatment of social phobia: a pilot study. AB - Twenty-three patients who met DSM-III-R criteria for social phobia were randomly assigned either to a clonazepam treatment group or to a nontreatment control group in an 8-week pilot study. Clonazepam was found to have a significant effect on the treated patients, as demonstrated by scores on a variety of instruments measuring overall anxiety and phobic avoidance, and social phobic symptoms. Initial sedation, which was experienced by 70% of the treated subjects, was the most common side effect of clonazepam treatment and usually resolved spontaneously or with dose reduction. The preliminary findings of this pilot study are sufficiently promising to warrant further study of the efficacy of clonazepam in this condition. PMID- 2186024 TI - Epidermal growth factor. PMID- 2186025 TI - Solubilization and reconstitution of the Na(+)-dependent citrate carrier of Klebsiella pneumoniae. AB - The citrate carrier of Klebsiella pneumoniae fermenting this substrate has been solubilized from the bacterial membranes with Triton X-100. The transport function was reconstituted by incorporation of the carrier into proteoliposomes using a freeze-thaw sonication procedure. Citrate uptake into these proteoliposomes required the presence of Na+ ions on the outside; the amount of citrate accumulated increased as the external Na+ concentration increased from 0 to 100 mM. Proteoliposomes preloaded with citrate catalyzed citrate counterflow when added to external [14C] citrate. Sodium ions were required for counterflow activity. The kinetics of citrate uptake, counterflow, or efflux were not influenced by an inside negative membrane potential, and the presence of the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone was without effect on citrate uptake. The data therefore suggest an electroneutral Na(+)-citrate symport mechanism for the transport of this tricarboxylic acid into K. pneumoniae. PMID- 2186026 TI - Thrombin binds to murine bone marrow-derived macrophages and enhances colony stimulating factor-1-driven mitogenesis. AB - The binding and mitogenic properties of thrombin have been established in various transformed cell lines. In such systems, thrombin induces cell division in the absence of exogenous growth factors, and the enzyme is considered to act directly as a mitogen. This study explores thrombin's interaction with nontransformed, growth factor-dependent cells. Binding of 125I-alpha-thrombin to colony stimulating factor (CSF)-1-dependent bone marrow-derived macrophages is saturable, time-dependent, and displaceable by both unlabeled alpha-thrombin, and esterolytically inactive thrombin. Both dissociation studies of pre-bound radio labeled thrombin and Scatchard analysis assisted by the program "Ligand" suggest adherence of thrombin-binding data to a multi-site model. There are an estimated 2 x 10(4) high affinity sites (Kd = 7 x 10(-9)M) and 2 x 10(6) low affinity sites (Kd = 9 x 10(-7)M) per cell. Quiescent bone marrow-derived macrophages were cultured with either 10(-8)M thrombin, 1000 units of CSF-1/ml, or both and [3H]thymidine incorporation was determined. Thrombin alone did not induce mitogenesis. CSF-1 induced mitogenesis with peak [3H] thymidine incorporation occurring 24 h after addition of the mitogen. This CSF-1-dependent mitogenic influence was enhanced greater than 2-fold by treatment with thrombin. PMID- 2186027 TI - Sensitive, soluble chromogenic substrates for HIV-1 proteinase. AB - By replacement of the P1' residue in a capsid/nucleocapsid cleavage site mimic with 4-NO2-phenylalanine (Nph), an excellent chromogenic substrate, Lys-Ala-Arg Val-Leu*Nph-Glu-Ala-Met, for HIV-1 proteinase (kappa cat = 20 s-1, Km = 22 microM) has been prepared. Substitution of the Leu residue in P1 with norleucine, Met, Phe, or Tyr had minimal effects on the kinetic parameters (kappa cat and kappa cat/Km) determined at different pH values, whereas peptides containing Ile or Val in P1 were hydrolyzed extremely slowly. The spectrophotometric assay has been used to characterize the proteinase further with respect to pH dependence, ionic strength dependence, and the effect of competitive inhibitors of various types. PMID- 2186028 TI - Dissection of the functional domains of Escherichia coli carbamoyl phosphate synthetase by site-directed mutagenesis. AB - The catalytic functions of the amino-terminal and carboxyl-terminal halves of the large subunit of carbamoyl phosphate synthetase from Escherichia coli have been identified using site-directed mutagenesis. Glycine residues at positions 176, 180, and 722 within the putative mononucleotide-binding site were replaced with isoleucine residues. Each of these mutations resulted in at least a 1 order of magnitude reduction in the Vmax for carbamoyl phosphate synthesis. The mutations on the amino-terminal half, G176I and G180I, caused slight reduction in the rate of synthesis of ATP from ADP and carbamoyl phosphate (the partial ATP synthesis reaction) but the bicarbonate-dependent ATPase reaction velocity was reduced to less than 10% of the wild-type rate. The mutant G722I, which is on the carboxy terminal half, caused the partial ATP synthesis reaction to be reduced by 1 order of magnitude but the bicarbonate-dependent ATPase reaction was reduced only slightly. All three mutations are within regions which show homology to the putative glycine-rich loops of many ATP-binding proteins. These results have been interpreted to suggest that the two homologous halves of the large subunit of carbamoyl phosphate synthetase each contain a binding site for ATP. The NH2 terminal domain contains the portion of the large subunit that is primarily involved with the phosphorylation of bicarbonate to carboxy phosphate while the COOH-terminal domain contains the region of the enzyme that catalyzes the phosphorylation of carbamate to carbamoyl phosphate. PMID- 2186029 TI - Isolation and characterization of the Drosophila nuclear envelope otefin cDNA. AB - We have recently identified and characterized a 53-kDa inner nuclear membrane associated protein in Drosophila and termed it otefin. Here we report the isolation and characterization of cDNA and genomic clones of the otefin gene. Based on sequence analysis, we deduced that the primary translation product has a calculated mass of 45 kDa, contains many serine and threonine residues, and is mostly hydrophilic. However, in the carboxyl terminus, there is a hydrophobic region which may serve as a membrane anchoring domain. RNA blot analysis indicated that the otefin gene codes for a single poly(A+) transcript of 1.6 kilobases and that relatively large amounts of this transcript are present during developmental stages in which many nuclear divisions occur. Polyclonal antibodies raised against the cDNA translation product react with a 58-kDa mammalian nuclear envelope protein, demonstrating evolutionary conservation. PMID- 2186030 TI - The ATP-dependent Clp protease of Escherichia coli. Sequence of clpA and identification of a Clp-specific substrate. AB - The clpA gene, which codes for the ATP-binding subunit of the ATP-dependent Clp protease of Escherichia coli, has been sequenced. The coding region contains a single open reading frame for a protein of 758 amino acids; within the amino acid sequence are two consensus sequences for ATP-binding sites. The sequence of ClpA does not resemble that of other previously described ATPases or Lon, the other sequenced ATP-dependent protease of E. coli, except in the ATP-binding site consensus region. The clpA gene is expressed as a monocistronic message. Primer extension experiments define a major start point of transcription at -183 relative to the start of translation. A rho-independent terminator is located 23 bases beyond the end of the coding region. The ClpA protein is degraded in vivo in a Clp-dependent fashion (t1/2 approximately 60 min). A fusion protein containing the first 40 amino acids of ClpA fused in frame to beta-galactosidase is degraded very rapidly in a clpA+ host (t1/2 approximately 3 min) but not in a clpA- host. This fusion protein is the first Clp-specific substrate described. PMID- 2186031 TI - Rat C1-tetrahydrofolate synthase. cDNA isolation, tissue-specific levels of the mRNA, and expression of the protein in yeast. AB - We have isolated and characterized cDNA clones encoding rat cytoplasmic C1 tetrahydrofolate (H4folate) synthase. In eukaryotes, this enzyme is trifunctional and contains the activities of 10-formyl-H4folate synthetase, 5,10-methenyl H4folate cyclohydrolase, and 5,10-methylene-H4folate dehydrogenase. The deduced sequence of the 935-amino acid open reading frame contained exact matches to NH2 terminal (15 residues) and internal (residues 436-450) peptide sequences obtained from the purified enzyme. The amino acid sequence derived from the rat cDNA shows extensive homology to analogous proteins from bacterial, yeast, and mammalian sources. We have used the cDNA to determine the steady-state levels of the mRNA in various rat tissues and have found that gene expression is regulated in a tissue-specific manner. Transcript levels are highest in kidney and liver with liver transcripts reduced about 30% relative to those found in kidney. Brain, heart, testis, lung and skeletal muscle display even lower transcript levels; reductions range from 70 to 80% of transcript levels found in kidney. Comparison to the levels of enzyme in these tissues allows us to conclude that pretranslational events predominate in the tissue-specific expression. The rat enzyme has been functionally expressed in Saccharomyces cerevisiae as evidenced by its capacity to complement a chromosomal deletion of ADE3, the yeast gene encoding cytoplasmic C1-H4folate synthase. PMID- 2186032 TI - 1,2-Diacylglycerol and ceramide levels in rat skeletal muscle and liver in vivo. Studies with insulin, exercise, muscle denervation, and vasopressin. AB - Studies on BC3H-1 myocytes suggest that the insulin-induced increase in cellular diacylglycerol level mediates the insulin-stimulated glucose transport in these cells (Standaert, M. L., Farese, R. V., Cooper, D. R., and Pollet, R. J. (1988) J. Biol. Chem. 263, 8696-8705). The present study tested whether diacylglycerol could mediate the insulin-induced and exercise-induced increases in glucose uptake by rat skeletal muscle in vivo. Glucose uptake by calf muscles of the rat was assessed by measuring cellular 2-deoxyglucose uptake in vivo. Diacylglycerol and ceramides in muscles frozen in situ were assayed with diacylglycerol kinase. Intravenous injection of 0.1 unit of insulin/rat resulted in a 6-fold increase in muscle 2-deoxyglucose uptake during the subsequent 25-min period. In contrast, no statistically significant changes in muscle diacylglycerol or ceramide levels were observed at 2, 5, 10, and 25 min after insulin injection. When calf muscles of the hindlimb were exercised in vivo for 25 min by electrical stimulation inducing one contraction/s, 2-deoxyglucose uptake by muscles was increased 15 fold. However, no statistically significant changes in muscle diacylglycerol or ceramide content were observed at 5, 10, 15, and 25 min of exercise. Although the findings do not exclude the possibility of a compartmentalized increase in diacylglycerol level, the present data suggest that diacylglycerol is not a mediator of the insulin-induced or exercise-induced augmentation of glucose uptake by skeletal muscle in vivo. Since interruption of nerve supply to the muscles makes the muscles insulin resistant (Turinsky, J., (1987) Am. J. Physiol. 252, R531-R537), the effect of denervation on diacylglycerol and ceramide levels in calf muscles of the rat was also examined. The denervation resulted in 21, 51, and 117% increases in muscle diacylglycerol levels at 3, 16, and 32 days after denervation, respectively. No statistically significant changes in muscle ceramide levels were observed at any postdenervation interval. Finally, the measured lipids were studied in muscles and livers of rats infused with supraphysiological doses of vasopressin (86 pmol/min). In controls, diacylglycerol concentrations of the muscles and liver did not significantly differ, but the liver exhibited a 5-fold higher level of ceramides than the muscles. Infusion of vasopressin for 5 min did not have a statistically significant effect on diacylglycerol concentration of the liver but continuation of the same infusion for 10 min resulted in a 63% increase in liver diacylglycerol. The 10-min infusion had no effect on muscle diacylglycerol concentration or ceramide levels in any of the tissues studied.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2186033 TI - Long term regulation of glucose transporters by insulin in mature 3T3-F442A adipose cells. Differential effects on two glucose transporter subtypes. AB - The question of a long term regulatory role of insulin on adipocyte glucose transporter content was addressed using the differentiating or fully mature 3T3 F442A adipocytes. Glucose transport was measured in intact cells. Glucose transporter content in plasma membranes and low density microsomes (LDM) was assessed by cytochalasin B binding and Western analysis. In insulin- versus spontaneously differentiated adipocytes, glucose transport and glucose transporters content of plasma membranes and LDM were increased 5-, 4-, and 2 fold, respectively. Insulin deprivation for 24 h induced a redistribution of glucose transporters in those cells which then displayed 2-fold higher glucose transport and glucose transporter content in plasma membranes than spontaneously differentiated cells and 3-fold more glucose transporters in LDM. When fully insulin-differentiated adipocytes were insulin-deprived for 4 days, there was a marked decrease in glucose transporters in both membrane fractions that was fully reversible by reexposing the cells to insulin for 4 days. Glucose uptake changes were closely proportionate to changes in glucose transporter content of plasma membranes as assessed by an antiserum to the C-terminal peptide of the erythrocyte/HepG2/brain-type glucose transporter. When Western blots were immunoblotted with 1F8 monoclonal antibody, specific for glucose transporter in insulin responsive tissues, an abundant immunoreactive protein was detected in both plasma membranes and LDM but the amount of this glucose transporter did not change with insulin exposure in any membrane fractions. In conclusion, insulin plays a long term regulatory role on cultured adipocyte glucose transporter content through a selective effect on the erythrocyte/HepG2/brain-type glucose transporter. PMID- 2186034 TI - The importance of loop region residues 40-46 in human dihydrofolate reductase as revealed by site-directed mutagenesis. AB - Site-directed mutagenesis has been used to delete 2 residues (Gly45-Lys46) from a flexible "loop" region between residues 40 and 46 of human dihydrolate reductase. Steady-state kinetic studies show that the Km values for the deletion mutant enzyme for both dihydrofolate and nicotinamide adenine dinucleotide phosphate (reduced) (NADPH) as well as the pH rate profile are virtually identical to that of the wild type. In contrast, the Vmax value of the mutant enzyme is decreased 2.5-fold. The results suggest that the loop region may play a role in the catalytic efficiency but not necessarily in the binding of substrates. Agents such as KCl, urea, and organomercurials at concentrations which show activating effects on the wild-type human dihydrofolate reductase have little or no effect on the deletion mutant. Competitive enzyme-linked immunosorbent assay experiments using peptide-specific antibodies against cyanogen bromide fragments generated from human dihydrofolate reductase show that the binding of folate, NADPH, and methotrexate, either in binary or in ternary complexes with the wild-type enzyme, causes a striking reduction in the binding of the antibodies. Compared with wild type, the binding of these ligands with the deletion mutant enzyme causes much less inhibition (2-16-fold less) in the binding of all three antibodies. The altered properties of the mutant enzyme can be explained on the basis of a need for the flexible loop 40-46 for reversible protein unfolding during activation and also for conformational changes induced by ligand binding, thus "communicating" the effects of ligand binding. PMID- 2186035 TI - Effects of anti-alpha monoclonal antibodies on initiation and elongation by the Escherichia coli RNA polymerase. AB - Anti-alpha monoclonal antibodies have been used to investigate the role of the alpha subunit of RNA polymerase in initiation and elongation. The four inhibitory monoclonal antibodies studied strongly inhibit cAMP receptor protein-dependent initiation with lac P+ and partially inhibit initiation directed by the lac UV5 promoter. The data suggest that the epitopes to which each of the monoclonal antibodies bind may be proximal to the contact domain between cAMP receptor protein and RNA polymerase. Recycling of RNA polymerase through the initiation process is slower in the presence of an inhibitory monoclonal antibody. Once a 9 nucleotide-long transcript has formed, incubation with the anti-alpha monoclonal antibody does not affect subsequent elongation. The monoclonal antibodies still bind to the elongation complex as indicated by sedimentation of the complex formed after incubation with Staphylococcus aureus cells (immunoprecipitin). These results suggest that the resistance of the elongation complex to these antibodies is not a consequence of their inability to bind to RNA polymerase. Only one of the alpha subunits may be involved in the initial process of transcription, and the antigenic domain of this subunit appears to be occluded by the nascent transcript present in the elongation complex. PMID- 2186036 TI - Isolation and characterization of extremely minor gangliosides, GM1b and GD1 alpha, in adult bovine brains as developmentally regulated antigens. AB - In addition to ganglioside GM1b, an unusual and extremely minor ganglioside, GD1 alpha, was efficiently isolated from bovine brain by combination of Q-Sepharose and Iatrobeads column chromatographies. In the course of purification steps, the presence of the sialidase-labile ganglioside was proved by a highly sensitive TLC/enzyme-immunostaining method. The structure was characterized by gas-liquid chromatography, permethylation study, sialidase degradation, immunostaining with specific antibodies, fast atom bombardment-mass spectrometry, and proton magnetic resonance spectrometry. The content of the ganglioside was very small (0.016%) in the total gangliosides. This finding suggests that a synthetic pathway of asialo GM1----GM1b----GD1 alpha may exist in mammalian brains. A monoclonal antibody NA 6 that was obtained by immunizing mice with purified GM1b reacted specifically with GM1b but showed no cross-reactivity with other structurally related gangliosides such as GM1a, GD1a, and so on. Using the method of TLC/immunostaining with NA-6, GM1b was found to be strongly expressed during embryonic days 14-17 in chick brains. Thus, it is assumed that extremely minor gangliosides like GM1b and GD1 alpha found in adult brains are characterized as embryonic molecules. PMID- 2186037 TI - Developmental expression of heme oxygenase isozymes in rat brain. Two HO-2 mRNAs are detected. AB - Blot hybridization of RNA isolated from rat brain revealed the presence of two HO 2 homologous transcripts (1.3 and 1.9 kilobases (kb] at all stages of development ranging from 1 day before birth to adulthood. The level of both HO-2 messages appeared to be developmentally regulated and a gradual increase was observed from prenatal day 1 to adulthood. The two transcripts were highly homologous as assayed through hybridization studies using probes derived from the 5' end, middle, and 3' end of a cloned rat testis HO-2 cDNA. The 1.3-kb mRNA was essentially identical in size to the testis HO-2 cDNA. The message was efficiently translated in the brain, and is believed to encode the HO-2 protein. It seems unlikely that the 1.9-kb species represents a precursor of the 1.3-kb mRNA, as it was also translated in vivo, although less efficiently than the smaller mRNA species. Neither of the two HO-2 mRNA species were induced by bacterial endotoxin. Unlike HO-2, only one HO-1 transcript of approximately 1.8 kb could be detected. This transcript was of very low abundance and was not developmentally regulated, but could be increased by bacterial endotoxin. The product of this induced message, however, was not detectable by Western immunoblot analysis using antibody raised against liver HO-1. An immunoprecipitate could be detected in brain microsomes by radioimmunoassay using the same antibody. This protein, however, exhibited antigenic properties different from that of the purified liver HO-1 or that of spleen microsomal HO-1. Brain heme oxygenase activity correlated well with the amount of immunoreactive HO-2 protein and both reflect the abundance of the 1.3-kb mRNA message over the course of development. PMID- 2186038 TI - Interaction of host cell proteins with the human T-cell leukemia virus type I transcriptional control region. II. A comprehensive map of protein-binding sites facilitates construction of a simple chimeric promoter responsive to the viral tax2 gene product. AB - We present a map describing the binding of cellular proteins to a 300-base pair (bp) region of the human T-cell leukemia virus type I (HTLV-I) long terminal repeat. The map accounts for nearly all of the DNase I protection reported in a previous study using crude nuclear extracts. Notable features include a complex arrangement of overlapping binding sites encompassing the 21-bp repeat elements (see accompanying paper) as well as binding sites for the transcription factors Sp1 and NF-I that significantly deviate from the previously defined consensus recognition sequences. Based on the binding results, we constructed simple chimeric promoters containing 21-bp repeat elements, Sp1-, and nuclear factor I binding sites upstream of a TATA box. Transient transfection experiments show that these promoters are expressed in T-cells and are regulated by the viral tax2 gene product. Deletion of the Sp1 and nuclear factor I sites abolishes tax induction, suggesting that one or both of these proteins play a role in mediating the tax-responsiveness conferred by the 21-bp repeat element. PMID- 2186039 TI - 500-Kilodalton calcium sensor regulating cytoplasmic Ca2+ in cytotrophoblast cells of human placenta. AB - Two monoclonal IgG antibodies E11 and G11, which react with parathyroid and kidney tubule cells, are in the present communication demonstrated to immunostain the surface of cytotrophoblast cells in human placenta. The G11 but not the E11 antibody has earlier been found to interfere with the sensing and gating of extracellular calcium in parathyroid cells. Microfluorometric measurement of the cytoplasmic calcium (Ca2+i) concentration was performed on suspended placental cells loaded with fura-2. The E11-positive placental cells displayed biphasic and parathyroid-like increases in Ca2+i in response to extracellular Ca2+. This increase was blocked by the G11 antibody and absent in the E11-negative placental cells. A sandwich enzyme-linked immunosorbent assay was constructed in which the G11 and E11 antibodies were shown to react with the same molecule. This calcium sensor was isolated and found to consist of a single, glycosylated polypeptide of approximately 500 kDa. PMID- 2186040 TI - Positive and negative regulation of the human insulin gene by multiple trans acting factors. AB - Tissue-specific expression of the human insulin gene is regulated by cis-acting DNA elements 5' to the transcription start site. Deletion of the 5' region of the human insulin gene between nucleotides -279 and -258 caused a 25-fold rise in transcriptional activity whereas further deletion to nucleotide -229 reduced transcription activity 25-fold. In vitro analysis of protein binding in the 5' regulatory region revealed: (i) the major positive regulatory region (-258 to 229) contains a protein-binding site (GC-II) with 75% sequence identity to a motif in the rat insulin I gene, shown to be a powerful transcriptional activator. GC-II motif-binding factors are not restricted to insulin-producing cell lines. (ii) An islet cell-specific factor binds between nucleotides -217 to 210 (CT-II motif). (iii) A region between nucleotides -153 and -127, containing two identical motifs, GG-I and GG-II was also revealed. GG-I-binding factors are ubiquitous, whereas binding to the GG-II motif is beta cell-specific. (iv) A ubiquitous factor binds to a motif between nucleotides -179 and -183, identical to a half-site for the cyclic nucleotide regulatory element. (v) The negative regulatory element between -279 and -258 contains overlapping binding sites for at least 3 protein factors, with differing cell-specific distributions and can independently down-regulate thymidine kinase promoter activity in a beta cell line. PMID- 2186041 TI - Characterization of a receptor for human monocyte-derived neutrophil chemotactic factor/interleukin-8. AB - Monocyte-derived neutrophil chemotactic factor/interleukin-8 (MDNCF/IL-8) is an 8,000-dalton protein produced by monocytes which exhibits activity as a chemoattractant for neutrophils with maximal activity achieved at a concentration of 50 ng/ml. This polypeptide has been iodinated by chloramine-T methodology (350 Ci/mM), and specific receptors for MDNCF/IL-8 have been detected on human neutrophils, U937 cells, THP-1 cells, and dimethyl sulfoxide-differentiated HL-60 cells. The binding of MDNCF/IL-8 to human neutrophils is not inhibited by interleukin-1 alpha, tumor necrosis factor-alpha, insulin, or epidermal growth factor. In addition, chemoattractants such as C5a, fMet-Leu-Phe, leukotriene B4, and platelet-activating factor fail to inhibit binding, suggesting that MDNCF/IL 8 utilizes a unique receptor. The receptor for MDNCF/IL-8 is apparently glycosylated since ligand binding is inhibited by the presence of wheat germ agglutinin, a lectin with a binding specificity for N-acetylglucosamine and neuraminic acid. Steady state binding experiments indicate Kd values of 4 and 0.5 nM and receptor numbers of 75,000 and 7,400 for human neutrophils and differentiated HL-60 cells, respectively. 125I-MDNCF/IL-8 bound to human neutrophils is rapidly internalized and subsequently released from cells as trichloroacetic acid-soluble radioactivity. Affinity labeling experiments suggest that the human neutrophil MDNCF/IL-8 receptor exhibits a mass of approximately 58,000 daltons. PMID- 2186042 TI - Protein kinase C-independent activation of nuclear factor kappa B by tumor necrosis factor. AB - Tumor necrosis factor (TNF) is one of the few physiological inducers of the pleiotropic transcription factor NF kappa B. NF kappa B may play a central role in mediating TNF's gene regulatory action; however, the molecular mechanisms of TNF-induced NF kappa B activation are poorly understood. In this study, we demonstrate with two human leukemic cell lines, K562 and Jurkat, that TNF induces rapid and transient activation and translocation of protein kinase C (PK-C) from the cytosol to the membranes, which is followed by the emergence of kappa B binding activity. In order to investigate whether TNF-mediated PK-C activation can be linked to induction of NF kappa B, we tried to block TNF action by use of various protein kinase C inhibitors as well as down-regulation of PK-C. Preincubation of Jurkat cells with protein kinase inhibitor H7 or staurosporine blocked PK-C activation by either TNF or phorbol 12-myristate 12-acetate (PMA). This pretreatment regimen completely inhibited NF kappa B activation by PMA. In contrast, TNF's ability to induce NF kappa B remained unaffected. In addition, NF kappa B was TNF-inducible in Jurkat cells depleted for PK-C by long-term exposure to high dose phorbol ester. The data indicate that PK-C is not required for NF kappa B activation by TNF and imply a novel, PK-C-independent mechanism of physiological NF kappa B activation. PMID- 2186043 TI - Dietary noncompliance in pediatric patients in the burn unit. PMID- 2186044 TI - Identification of a Golgi-associated protein that undergoes mitosis dependent phosphorylation and relocation. AB - By means of a monoclonal antibody (BH3), we have identified a 57-kD protein (p57) that in interphase is restricted largely to the perinuclear region of the cell. Double label immunofluorescence microscopy suggests localization of p57 to the Golgi complex and associated membranous structures. Protease protection experiments and chemical extractability indicate that p57 is a peripheral membrane protein exposed to the cytoplasm. p57 displays unique behavior during mitosis. At the end of G2 or in early prophase, p57 leaves the perinuclear region and accumulates very rapidly within the nucleus, at a time when the nuclear envelope is still intact and before nuclear lamina disassembly. This relocation of p57 coincides with its hyperphosphorylation on serine and threonine residues. After nuclear envelope breakdown p57 becomes uniformly distributed throughout the mitotic cytoplasm until in late telophase when it returns to its perinuclear location and is once again excluded from the nucleus. The behavior of p57 during mitosis suggests that it may play a role in the cellular reorganization evident during mitotic prophase. PMID- 2186045 TI - Identification of an activator required for elevation of maturation-promoting factor (MPF) activity by gamma-S-ATP. AB - Maturation-promoting factor (MPF) is a cell cycle control element able to cause cells to enter M-phase upon microinjection and will induce metaphase in nuclei incubated in cell extracts. Previous work has shown that MPF is composed of a complex between p34cdc 2 protein kinase and a B-type cyclin. In the present work gamma-S-ATP was found to cause activation of MPF activity in partially purified preparations, but this activation was lost upon chromatography on Matrex Green gel A. Readdition of other Matrex Green fractions to purified MPF restored the ability of gamma-S-ATP to activate MPF for nuclear breakdown as well as phosphorylation of histone H1. Use of the system described here will facilitate study of p34cdc 2 kinase activation and identification of elements involved in MPF regulation. PMID- 2186046 TI - Modulation of microtubule stability by kinetochores in vitro. AB - The interface between kinetochores and microtubules in the mitotic spindle is known to be dynamic. Kinetochore microtubules can both polymerize and depolymerize, and their dynamic behavior is intimately related to chromosome movement. In this paper we investigate the influence of kinetochores on the inherent dynamic behavior of microtubules using an in vitro assay. The dynamics of microtubule plus ends attached to kinetochores are compared to those of free plus ends in the same solution. We show that microtubules attached to kinetochores exhibit the full range of dynamic instability behavior, but at altered transition rates. Surprisingly, we find that kinetochores increase the rate at which microtubule ends transit from growing to shrinking. This result contradicts our previous findings (Mitchison, T. J., and M. W. Kirschner, 1985b) for technical reasons which are discussed. We suggest that catalysis of the growing to shrinking transition by kinetochores may account for selective depolymerization of kinetochore microtubules during anaphase in vivo. We also investigate the effects of a nonhydrolyzable ATP analogue on kinetochore microtubule dynamics. We find that 5' adenylylimido diphosphate induces a rigor state at the kinetochore-microtubule interface, which prevents depolymerization of the microtubule. PMID- 2186047 TI - Intramitotic controls in the fission yeast Schizosaccharomyces pombe: the effect of cell size on spindle length and the timing of mitotic events. AB - We have used a new cinemicroscopy technique in combination with antitubulin immunofluorescence microscopy to investigate the timing of mitotic events in cells of the fission yeast Schizosaccharomyces pombe having lengths at division between 7 and 60 microns. Wild-type fission yeast cells divide at a length of 14 microns. Separation of daughter nuclei (anaphase B) proceeds at a rate of 1.6 +/- 0.2 microns min-1, until the spindle extends the length of the cell. Coincident with spindle depolymerization, the nuclei reverse direction and take up positions that will become the center of the two daughter cells. This post-mitotic nuclear migration occurs at a rate of 1.4 +/- 0.5 microns-1. In cells in which the weel+ gene is overexpressed fivefold and that have an average length at mitosis of 28 microns, the rate of nuclear separation was only slightly reduced but, as spindles in these cells measure 20-22 microns, the duration of anaphase B was extended by approximately 40%. By contrast, in the mutant weel.50, which divides at 7 microns, both the rate and duration of anaphase B were indistinguishable from wild type. Nuclei reach the ends of these cells earlier but remain there until a point corresponding to the time of postmitotic nuclear migration in wild type. Thus, the events of mitosis can be extended but not abbreviated. These results are discussed in terms of a mitotic termination control that monitors many different events, one of which is spindle elongation. PMID- 2186048 TI - Olfactory neurons express a unique glycosylated form of the neural cell adhesion molecule (N-CAM). AB - mAb-based approaches were used to identify cell surface components involved in the development and function of the frog olfactory system. We describe here a 205 kD cell surface glycoprotein on olfactory receptor neurons that was detected with three mAbs: 9-OE, 5-OE, and 13-OE. mAb 9-OE immunoreactivity, unlike mAbs 5-OE and 13-OE, was restricted to only the axons and terminations of the primary sensory olfactory neurons in the frog nervous system. The 9-OE polypeptide(s) were immunoprecipitated and tested for cross-reactivity with known neural cell surface components including HNK-1, the cell adhesion molecule L1, and the neural cell adhesion molecule (N-CAM). These experiments revealed that 9-OE-reactive molecules were not L1 related but were a subset of the 200-kD isoforms of N-CAM. mAb 9-OE recognized epitopes associated with N-linked carbohydrate residues that were distinct from the polysialic acid chains present on the embryonic form of N CAM. Moreover, 9-OE N-CAM was a heterogeneous population consisting of subsets both with and without the HNK-1 epitope. Thus, combined immunohistochemical and immunoprecipitation experiments have revealed a new glycosylated form of N-CAM unique to the olfactory system. The restricted spatial expression pattern of this N-CAM glycoform suggests a possible role in the unusual regenerative properties of this sensory system. PMID- 2186049 TI - Mapping enteroendocrine cell populations in transgenic mice reveals an unexpected degree of complexity in cellular differentiation within the gastrointestinal tract. AB - The gastrointestinal tract is lined with a monolayer of cells that undergo perpetual and rapid renewal. Four principal, terminally differentiated cell types populate the monolayer, enterocytes, goblet cells, Paneth cells, and enteroendocrine cells. This epithelium exhibits complex patterns of regional differentiation, both from crypt-to-villus and from duodenum-to-colon. The "liver" fatty acid binding protein (L-FABP) gene represents a useful model for analyzing the molecular basis for intestinal epithelial differentiation since it exhibits cell-specific, region-specific, as well as developmental stage specific expression. We have previously linked portions of the 5' nontranscribed domain of the rat L-FABP gene to the human growth hormone (hGH) gene and analyzed expression of the fusion gene in adult transgenic mice. High levels of hGH expression were noted in enterocytes as well as cells that histologically resembled enteroendocrine cells. In the present study, we have used immunocytochemical techniques to map the distribution of enteroendocrine cells in the normal adult mouse gut and to characterize those that synthesize L-FABP. In addition, L-FABP/hGH fusion genes were used to identify subsets of enteroendocrine cells based on their ability to support hGH synthesis in several different pedigrees of transgenic mice. The results reveal remarkable differences in transgene expression between, and within, enteroendocrine cell populations previously classified only on the basis of their neuroendocrine products. In some cases, these differences are related to the position occupied by cells along the duodenal-to-colonic and crypt-to-villus axes of the gut. Thus, transgenes appear to be sensitive tools for examining the cellular and regional differentiation of this class of intestinal epithelial cells. PMID- 2186050 TI - In vivo analyses of integrin beta 1 subunit function in fibronectin matrix assembly. AB - Early development of the urodele amphibian Pleurodeles waltl is accompanied by a process of progressive fibronectin (FN) fibrillogenesis. FN begins to assemble into fibrils on the inner surface of the blastocoele roof at the early blastula stage and progressively forms a complex extracellular matrix. We have analyzed the mechanisms of FN-fibril formation under normal and experimental conditions in vivo with the following probes: iodinated FN, fluorescein-labeled FN, synthetic peptides containing the Arg-Gly-Asp (RGD) cell surface recognition sequence of FN, and polyclonal antibodies against both beta 1 subunit of the amphibian FN receptor and the cytoplasmic domain of beta 1 subunit. We report that in living embryos, exogenous labeled mammalian FN injected into the amphibian blastocoele undergoes FN-fibril formation in spatiotemporal patterns similar to those of endogenous FN. This indicates regulation of fibrillogenesis by the cell surface rather than by changes in the type of FN. Fibrillogenesis is inhibited in a dose dependent manner both by the GRGDS peptide and monospecific antibodies to amphibian integrin beta 1 subunit. Furthermore, when injected intracellularly into uncleaved embryos or into selected blastomeres, antibodies to the cytoplasmic domain of integrin beta 1 subunit produce a reversible inhibition of FN-fibril formation that follows early cell lineages and cause delays in development. Together, these data indicate that in vivo, the integrin beta 1 subunit and the RGD recognition signal are essential for the proper assembly of FN fibrils in early amphibian development. PMID- 2186052 TI - Clinical review 8: Clinical heterogeneity of involutional osteoporosis: implications for preventive therapy. PMID- 2186051 TI - Yeast KRE genes provide evidence for a pathway of cell wall beta-glucan assembly. AB - The Saccharomyces cerevisiae KRE1 gene encodes a Ser/Thr-rich protein, that is directed into the yeast secretory pathway, where it is highly modified, probably through addition of O-linked mannose residues. Gene disruption of the KRE1 locus leads to a 40% reduced level of cell wall (1----6)-beta-glucan. Structural analysis of the (1----6)-beta-glucan fraction, isolated from a strain with a krel disruption mutation, showed that it had an altered structure with a smaller average polymer size. Mutations in two other loci, KRE5 and KRE6 also lead to a defect in cell wall (1----6)-beta-glucan production and appear to be epistatic to KRE1. These findings outline a possible pathway of assembly of yeast cell wall (1 ---6)-beta-glucan. PMID- 2186053 TI - Analysis of gonadotropin-releasing hormone gene structure in families with familial central precocious puberty and idiopathic hypogonadotropic hypogonadism. AB - We examined the GnRH gene structure in a family with familial central precocious puberty (eight members, four affected) and a family with idiopathic hypogonadotropic hypogonadism (eight members, three affected) using Southern blot analysis and sequencing of cloned polymerase chain reaction products. Genomic DNA samples were digested with restriction enzymes and hybridized to the human placental GnRH cDNA probe. BamHI digests revealed 6.5- and 2.7-kilobase (kb) bands; BglII, 6.0- and 4.0-kb bands; Ncol, 8.0- and 3.5-kb bands; Pstl, 4.2-kb, 2.8-kb, 1.3-kb and 950-basepair bands; XbaI, 6.5- and 5.0-kb bands. These sizes were the same as those found by this analysis in normal individuals. All family members with familial central precocious puberty or idiopathic hypogonadotropic hypogonadism showed the same size bands, except for one unaffected member of the family with idiopathic hypogonadotropic hypogonadism who had an additional band at 5.5 kb after digestion with NcoI, which is thought to be a rare polymorphism. Sequencing of exon 2 of the GnRH gene from these families, including the exon intron borders, revealed a polymorphism in the signal sequence of GnRH that predicts an amino acid change from tryptophan (nucleotide sequence: TGG) to serine (TCG) at the -8 position of the GnRH preprohormone. Although this polymorphism did not cosegregate with the clinical disorder in either family, this novel polymorphism may prove useful in the evaluation of linkage to the GnRH gene in other families with pubertal disorders. No other nucleotide sequence abnormality was found in 1.2 kb of the 5' flanking region or the four exons and their splice sites. PMID- 2186054 TI - Disproportionately elevated proinsulin in Pima Indians with noninsulin-dependent diabetes mellitus. AB - Fasting serum total immunoreactive insulin (IRI), true insulin, and true proinsulin (PI) were measured in 169 Pima Indians. The relationship of these variables to glucose tolerance, obesity, and parental diabetes was studied. Seventy-seven subjects had normal glucose tolerance, 46 had impaired glucose tolerance (IGT), and 46 had noninsulin-dependent diabetes mellitus (NIDDM) by WHO criteria. In subjects with normal glucose tolerance, the geometric mean ratio of PI to IRI (PI/IRI) was 10.8% (arithmetic mean, 12.5%), similar to that reported in other ethnic groups with lower prevalence rates of NIDDM. Parental diabetes had no effect on PI/IRI. Obese persons (body mass index, greater than or equal to 27 kg/m2) with normal glucose tolerance had PI/IRI of 9.3% compared with 16.3% for the nonobese (P less than 0.001), and PI/IRI was negatively correlated with body mass index (r = -0.34; P = 0.002). Proinsulin was disproportionately elevated in NIDDM (geometric mean PI/IRI, 19.9%; arithmetic mean, 23.6%), and the degree of elevation was related to the severity of hyperglycemia, but not the duration of diabetes. Subjects with IGT were more obese and had higher fasting plasma glucose (5.7 vs. 5.2 mmol/L; P = 0.025), true insulin (250 vs. 125 pmol/L; P less than 0.001), and PI concentrations (26 vs. 15 pmol/L; P less than 0.001) than those with normal glucose tolerance but similar mean PI/IRI (9.4 vs. 10.8%; P = 0.4). These findings indicate that Pima Indians with NIDDM have a disproportionate elevation of PI consistent with the hypothesis that beta-cell dysfunction associated with hyperglycemia leads to the release of proinsulin-rich immature granules. PMID- 2186055 TI - A randomized study of SMS 201-995 versus bromocriptine treatment in acromegaly: clinical and biochemical effects. AB - Twenty-six acromegalic patients were randomized to treatment with either SMS 201 995 or bromocriptine in increasing doses and were investigated before treatment, after 2, 4, and 8 weeks of treatment, and 2 weeks after discontinuation of treatment. There were two dropouts from the bromocriptine group and one from the SMS 201-995 group. Amelioration of clinical signs and symptoms was seen in both groups during treatment. After 8 weeks mean 12-h GH concentrations had declined from 13.8 +/- 5.2 to 2.9 +/- 4.4 (mean +/- SEM) in SMS 201-995-treated and from 18.8 +/- 7.5 to 5.4 +/- 1.2 micrograms/L in bromocriptine-treated patients. Somatomedin-C concentrations fell from 3.04 +/- 0.36 to 1.43 +/- 0.36 in SMS 201 995-treated and from 2.93 +/- 0.40 to 2.13 +/- 0.27 U/mL in bromocriptine-treated patients. Size reduction of the pituitary tumor was seen in one patient receiving bromocriptine. Gastrointestinal glucose absorption was delayed, and insulin secretion suppressed during treatment with SMS 201-995. Hemoglobin-A1 concentrations remained unchanged in SMS 201-995-treated patients, but declined in the bromocriptine group. Side-effects were common, but usually tolerable, with both treatments. It is concluded that both drugs are of benefit in the treatment of acromegaly. PMID- 2186056 TI - Female pseudohermaphroditism due to a maternal adrenocortical tumor. AB - A 15-yr-old, apparently male, patient presented with a 2-yr history of gynecomastia and poor genital development. A normally formed, but small, penis with a phallic urethra was present, and testes were impalpable. The karyotype was 46,XX, and at laparotomy a uterus, Fallopian tubes, and ovaries were found, but there was no testicular tissue. The mother had had regular periods ever since menarche at 14 yr. She had complained of hirsutism since the birth of the child, and on examination 15 yr later had marked clitoromegaly. Serum androgens were elevated: testosterone, 4.5 nmol/L (normal, 0.5-3); dehydroepiandrosterone sulfate, 18 mumol/L (normal, 3-12); and androstenedione, 35 nmol/L (normal, 3-8). All failed to suppress with dexamethasone. Abdominal computed tomographic scan revealed a 9 X 6-cm mass in the position of the left adrenal gland. This was removed at laparotomy and found to be an adrenocortical tumor. Postoperatively, the androgens returned to normal. Virilization of a female fetus due to androgens secreted by a maternal adrenal tumor has only been described three times previously, and the presentation has never been delayed so long. PMID- 2186057 TI - Partial characterization of a novel growth factor from the blood of women with preeclampsia. AB - Sera obtained before delivery from women with preeclampsia contain greater mitogenic activity than sera drawn from the same women 24-48 h after parturition or sera from normal parturients. These studies describe the initial characterization of the blood-borne mitogenic factor(s) from preeclamptic women which we have named ELMER (Endogenous Ligand conferring MitogEnic Response). ELMER appears to be a unique mitogen with characteristics that are not identical to those of other known growth factors. ELMER is present in serum as an acid- and heat-labile protein, approximately 160,000 daltons in size, which is a potent mitogen for human fibroblasts but not for human endothelial cells. Its presence in plasma suggests that it is a circulating factor rather than a product of blood coagulation ex vivo. We believe that ELMER represents a potential serum marker of preeclampsia and that it may play roles in the vasospasm and proliferative vascular lesion, termed atherosis, frequently associated with the preeclamptic syndrome. PMID- 2186058 TI - Regulation of pancreatic endocrine function by cholecystokinin: studies with MK 329, a nonpeptide cholecystokinin receptor antagonist. AB - A cholecystokinin (CCK) receptor antagonist, MK-329, was used to explore the physiological role of CCK in regulating pancreatic endocrine function in humans. The ability of CCK to increase plasma pancreatic polypeptide (PP) concentrations and blockade of this effect with MK-329 were evaluated in a double blind, balanced, four-period cross-over study. Eight subjects received single oral doses of 0.5, 2, or 10 mg MK-329 or placebo, followed by an iv infusion of CCK-8 (34 ng/kg.h). In placebo-treated subjects, PP increased from basal levels of 70 +/- 15 (+/- SE) to peak values of 291 +/- 58 pg/mL after CCK infusion (P less than 0.05 compared to basal). This increase in plasma PP concentration was inhibited in a dose-dependent fashion by MK-329, with 10 mg antagonizing the stimulatory effect of CCK infusion by nearly 80%. Second, the effect of MK-329 on meal stimulated pancreatic endocrine responses was evaluated by giving placebo or 10 mg MK-329 2 h before ingestion of a mixed meal. Eight subjects were treated in a randomized two-period cross-over fashion. With placebo treatment, peak postprandial plasma insulin, glucagon, and glucose concentrations were 101 +/- 8 microU/mL, 195 +/- 15 pg/mL, and 150 +/- 10 mg/dL, respectively (all P less than 0.05). The integrated PP response following the meal was 56.3 +/- 11.1 ng/mL.minute. With MK-329 treatment, the integrated PP concentration was reduced to 33.9 +/- 2.2 ng/mL.min (P less than 0.05 compared to placebo treatment). Mean postprandial insulin, glucagon, and glucose concentrations did not differ between placebo and MK-329 treatments. We conclude that CCK receptor blockade with 10 mg MK-329 does not alter plasma insulin, glucagon, or glucose responses to a mixed meal. However, the observation that physiological concentrations of CCK increase plasma levels of PP, and the finding that CCK receptor blockade selectively attenuates the postprandial increase in plasma PP concentrations support a physiological role for CCK in regulating PP secretion. PMID- 2186060 TI - Intraepidermal neutrophilic IgA dermatosis. AB - We report a patient with a vesiculopustular eruption with features distinct from typical subcorneal pustular dermatosis. Clinically, well-formed pustular lesions, which were flowerlike in appearance, were present. Histopathologically, early vesicular lesions showed intraepidermal bullae containing numerous neutrophils, a few eosinophils, and acantholytic cells. Direct immunofluorescence study revealed IgA deposits in the intercellular space of the epidermis. The patient's serum, however, did not contain circulating antibodies reactive with the epidermis. We consider this eruption an immunologically mediated, intraepidermal blistering disease, similar to intraepidermal neutrophilic IgA dermatosis. PMID- 2186059 TI - Serum growth hormone levels measured by radioimmunoassay and radioreceptor assay: a useful diagnostic tool in children with growth disorders? AB - Serum GH levels were measured by RIA and RRA in 133 subjects (19 healthy controls and 114 patients with various growth disturbances, aged 2.3-24.8 yr). Serum samples obtained from 147 stimulation tests representing a total of 1065 samples were analyzed by both methods, and the results compared. The data are expressed in absolute values and in RRA/RIA ratios. The area under the curve after a stimulation test (area GH) was calculated by planimetry. RIA was performed by the classical double antibody method using a polyclonal anti-serum. For the RRA, human cultured lymphocytes (IM-9 cells) were used, and 125I-labeled human GH was purified by high performance liquid chromatography. The same human GH standard was used in both assay systems. In control subjects a significant (P less than 0.0001) positive correlation was found at all ages between GH levels measured by RIA and RRA (r = 0.69 after insulin and r = 0.77 after glucagon). The RRA/RIA ratio (mean +/- SEM) for the peak GH level was 0.88 +/- 0.05, and the area under the GH curve was 0.85 +/- 0.05. The peak mean RRA/RIA ratios were significantly lower (P less than 0.05 and P = 0.03, respectively). No relationship was found with the absolute value of either peak or area GH. In patients with growth delay and Turner's syndrome, lower GH levels were found than in control subjects in both assay systems. The RRA/RIA ratios were also lower. In the other patients with some growth disorder, normal GH levels and ratios were found. In patients with renal failure, high levels of RIA-GH and RRA-GH were found, with a normal RRA/RIA ratio. In patients with documented pituitary GH deficiency, GH-releasing factor administration resulted in an increase in GH levels that was identical in both assays. The RRA/RIA ratio remained constant throughout the test. No correlation was found between the ratio and the absolute value of either RIA-GH or RRA-GH regardless of the stimulation test used. It is concluded that the presence of an abnormal GH molecule is extremely rare in patients with short stature. Thus, the presence of a bioinactive hormone is not a common cause of growth failure. During provocative testing some changes in the ratio may occur that do not appear after GH-releasing factor, further illustrating the different mechanisms involved in GH secretion. PMID- 2186061 TI - Hermansky-Pudlak syndrome: case report and clinicopathologic review. AB - The Hermansky-Pudlak syndrome is an autosomal recessive disorder consisting of the triad of albinism, a bleeding diathesis, and ceroid deposition within the reticuloendothelial system. In this study of a patient with Hermansky-Pudlak syndrome, we demonstrate the presence of ceroid within dermal macrophages. Electron microscopic studies suggest that melanosomes may be a substrate for the formation of ceroid in the skin. A review of the clinical and pathophysiologic features of this disorder is presented. PMID- 2186062 TI - Hodgkin's disease presenting in the skin: case report and review of the literature. AB - Cutaneous manifestations of Hodgkin's disease are relatively uncommon. We present a case of Hodgkin's disease with widespread skin involvement and review the literature on the subject. PMID- 2186063 TI - Large infiltrating renal transitional cell carcinomas: CT and ultrasound features. AB - A series of nine patients with large infiltrating renal transitional cell carcinomas is presented. These large tumors are rare but important in the differential diagnosis of renal masses. The average tumor size was 8.5 cm. In six patients the tumor involved almost the entire kidney. Seven masses were centrally located but two were peripheral. With CT the masses exhibited low attenuation relative to the normal or opposite renal parenchyma. Four masses exhibited necrosis. Lymphadenopathy, venous invasion, calcification, and spontaneous hemorrhage were all seen in this series. The major differential diagnostic possibility was renal cell carcinoma but lymphoma and metastatic disease were included. The diagnosis was confirmed in six patients by fine needle aspiration biopsy because of the presence of metastatic disease or the possibility of lymphoma. In the remaining three patients the diagnosis was made at surgery. The recognition that a large infiltrating renal mass may represent a transitional cell neoplasm is important in the eventual surgical management, and accurate preoperative diagnosis is stressed. PMID- 2186064 TI - Performance characteristics of an eight-ring whole body PET scanner. AB - The technical characteristics of the multislice whole-body positron emission tomographic scanner (model PC4096-15WB Scanditronix) and its performance parameters are described. Spatial resolution at the center of the field of view was found to be 4.9 mm in-plane and 4.6 mm (cross slices) and 6.0 mm (direct slices) in the axial direction. The sensitivity for true and scattered coincidences is approximately 5,000 cps for direct slices and 7,100 cps for cross slices. At an activity concentration of 37 kBq/ml the system deadtime was approximately 5%. By measuring a uniform phantom with a cold cylindrical insert (5.0 cm diameter), the scatter fraction was found to be approximately 5%. The mean global uniformity over all 15 slices was 6.5%, whereas the local uniformity was found to be 4.3%. No systematic nonuniformities were observed. Finally, various methods for attenuation correction (transmission scan, contour finding, ellipse) were utilized to test their effects on the resulting reconstructed images. PMID- 2186065 TI - CT and ultrasound of gallbladder adenomyomatosis mimicking carcinoma. PMID- 2186066 TI - Placebo-controlled evaluation of abbreviated progressive muscle relaxation and of relaxation combined with cognitive therapy in the treatment of tension headache. AB - Sixty-six tension headache patients were randomly assigned to one of four conditions for 8 weeks: (a) progressive muscle relaxation (PMR) alone; (b) PMR plus cognitive therapy (PMR + Cog); (c) pseudomeditation, a credible attention placebo control; or (d) continued headache monitoring. A comparison of overall headache activity (headache index), derived from a daily headache diary, for 4 weeks before treatment to 4 weeks after treatment, revealed that active treatment (PMR and PMR + Cog) was superior to either control condition. Moreover, level of headache medication consumption decreased significantly for the active treatment groups. Although headache-index comparisons of the two active treatments showed no advantage for adding cognitive therapy to PMR, a measure of clinically significant change showed a trend for PMR + Cog to be superior to PMR alone. PMID- 2186067 TI - A controlled evaluation of thermal biofeedback and thermal biofeedback combined with cognitive therapy in the treatment of vascular headache. AB - One-hundred-sixteen patients suffering from vascular headache (migraine or combined migraine and tension) were, after 4 weeks of pretreatment baseline headache monitoring, randomly assigned to one of four conditions: (a) thermal biofeedback with adjunctive relaxation training (TBF); (b) TBF plus cognitive therapy; (c) pseudomediation as an ostensible attention-placebo control; or (d) headache monitoring. The first three groups received 16 individual sessions over 8 weeks, while the fourth group continued to monitor headaches. All groups then monitored headaches for a 4-week posttreatment baseline. Analyses revealed that all treated groups improved significantly more than the headache monitoring group with no significant differences among the three treated groups. On a measure of clinically significant improvement, the two TBF groups had slightly higher (51%) degree of improvement than the meditation group (37.5%). It is argued that the attention-placebo control became an active relaxation condition. PMID- 2186068 TI - A histological comparison in the dog of porous-coated vs. threaded dental implants. AB - The histological findings of an 18-month trial, in the dog of a partially porous coated endosseous dental implant made of Ti-6Al-4V, with a truncated conical shape, are described and compared with those for a cylindrical, threaded, endosseous implant made of commercially pure Ti. Six beagle dogs each received two porous-coated implants on one side of the mandible and two threaded implants on the contralateral side. Each set of two implants supported a two-unit fixed bridge for an 18-month functional period. Methylmethacrylate sections of both the buccolingual and mesiodistal aspects of each implant were examined qualitatively and by computer-assisted morphometry. The morphometric measurements were used for determination of the length of implant surface in direct contact with bone on each aspect of each implant. The data were expressed both as an absolute length and as a fraction of the maximum length available for contact (contact length fraction or CLF). On the buccal and lingual aspects of the implants, both the absolute lengths and CLF were significantly smaller for the porous-coated design. For the mesial and distal aspects, the absolute lengths and CLF were less for the porous-coated design, but the differences were not significant. However, when the absolute contact length was related to the corresponding vertical bone height, significant differences were observed, the absolute contact length being greater for any given bone height for the porous-coated design. Taken together, the data suggest that shorter implants may be used with the porous-coated design. PMID- 2186069 TI - Microbiology of root surface caries in humans. AB - Studies on the microbiology of root surface caries between 1970 and 1975 placed emphasis on Gram-positive pleomorphic filamentous rods, particularly Actinomyces viscosus and Actinomyces naeslundii. Both of these species had been shown to produce root surface caries in experimental animals. Since this time, studies have placed more emphasis on Streptococcus mutans, and S. mutans and Lactobacillus are significant in prediction of root surface caries risk in patients. Subsequent studies confirmed an association between S. mutans and 'soft' or 'initial' root lesions. Thus, it is important when determining the microflora of root surface lesions to make careful characterization of the state of the lesion. A second important aspect of the analysis of bacterial communities associated with root surface caries is better definition of the organisms. Most studies have concentrated on 'target organisms' S. mutans, S. sanguis, A. viscosus, A. naeslundii, Lactobacillus, and Veillonella. However, it has been known for 17 years that the Actinomyces associated with the lesions may be variants of A. viscosus and A. naeslundii. Such strains (intermediate strains) have been described in taxonomic studies of Actinomyces, yet little is known of the differences in physiology of these strains or their relationship to root surface caries. A similar situation exists with oral Streptococcus where new taxonomic divisions are being proposed. Recognition of the potential diversity within the 'target' genera of root surface caries could yield valuable data. Recent studies suggest that this is so, since samples from root surface lesions which contain S. mutans and Lactobacillus show a high isolation of S. mitis 1 and no isolations of A. naeslundii. Careful definition of the lesions of root surface caries and the flora will allow analysis to relate a specific bacterial community to the state fo the lesion and assist in monitoring the control of the lesion through fluoride and antibacterials. PMID- 2186070 TI - The epidemiology of root surface caries. AB - Although a secular decline is being seen in coronal caries in children in industrialized countries, there appears to be a relatively high prevalence of root caries, with chronologically older adults exhibiting the highest prevalences. This paper reviews the descriptive and analytical epidemiology of root caries as found in recent national, regional, and local studies. A review of the variety of study designs, populations surveyed, and epidemiologic criteria for root caries comprising recent studies is presented as a background for comparison of prevalence rates which range from 7.3% to 69.7% of the population with root decay. In the few incidence studies reported, attack rates range from 1.6 surfaces per 100 surfaces at risk to 6.3 per 1000 surface-months at risk. Risk indicators for root caries are also reviewed with studies applying multivariate techniques implicating age, fluoride, educational level, use of dental services, coronal caries, loss of attachment, and number of teeth as possible risk factors. Although incidence studies have isolated risk factors, the small number of studies result in little agreement. Risk factor models from the Iowa 65+ Oral Health Study and a Risk Indicator model from the Piedmont 65+ Dental Study are presented to illustrate the variety of factors that may be involved in the expression of root surface caries in human populations. PMID- 2186071 TI - Indices of root surface caries. AB - Despite the increasing international interest in recent years in the epidemiology of root surface caries, there is no agreement on the diagnostic criteria to be used when the condition is recorded. In this paper the different methods used by dental epidemiologists are reviewed. It is shown that the wide variation in the levels of root surface caries recorded among different populations could be due to differences in the diagnostic methods as well as to inherent differences in the prevalence of the condition. It is recommended that an attempt be made to reach a global consensus on the methods of diagnosing root surface caries. Also, it is suggested that in reports of epidemiological studies of root surface caries, a basic set of tables including details of tooth loss be included. PMID- 2186072 TI - CAD-CAM ceramic inlays and onlays: a case report after 3 years in place. AB - At least three different techniques are available for preparing computer-aided designed (CAD) and computer-aided manufactured (CAM) inlays and veneers. This paper details a clinical case in which 13 Cerec CAD-CAM inlays have been functioning for 3 years. Advantages and limitations of this system are discussed. PMID- 2186073 TI - Optimal etching time of glass ionomer cement for maximum bond of composite resin. AB - This study compares the bond strengths of a composite resin to a glass ionomer cement with two types of surfaces and four etching times and attempted to correlate the bond strengths with a scanning electron microscope (SEM). The bond strengths were significantly greater to the instrumented surface at all etching times and the composite resin would not bond to glass smooth, unetched glass ionomer. PMID- 2186074 TI - Composite resin short-post technique for primary anterior teeth. AB - A technique using a "mushroom shaped" composite resin short post constructed inside the pulp-treated root canal provides sufficient retention to build a composite resin crown on the reinforced superstructure of the remaining crown dentin. This technique was tested for 1 year in 92 teeth; they showed no failures of retention of the short post. Recurrent caries and severe bruxism--factors beyond operator control--posed some problems that were readily resolved. PMID- 2186075 TI - Guidelines for the restoration of endodontically treated teeth. AB - Much confusion exists in the dental community regarding the restoration of endodontically treated teeth; few review articles present succinct guidelines for the restoration of these teeth. This article reviews the literature and presents guidelines for restoration of endodontically treated teeth. PMID- 2186076 TI - Dentistry on stamps. Santiago Ramon y Cajal. PMID- 2186077 TI - Vinyl polysiloxane impression materials: a status report. Council on Dental Materials, Instruments, and Equipment. AB - Results of investigations of vinyl polysiloxanes indicate that they produce highly accurate impressions, have excellent elastic recovery, minimal permanent deformation, and adequate tear strength. A number of vinyl polysiloxanes are certified by the American Dental Association. All of these materials provide clinically acceptable results. Advantages of using the vinyl polysiloxanes include the ability of the impression to be poured up after 1 hour or 1 day, or for some products, after 1 week without significant loss of accuracy; the possibility of repouring the impression a second time and producing an accurate cast; the impression materials are available in several viscosities allowing flexibility in choosing an impression technique; and they can be immersed in recommended disinfectants without affecting the accuracy of the impression. The disadvantages of using the vinyl polysiloxanes include a difficulty in lengthening the working time of products without retarders and a high surface tension making it difficult to wet the impression when pouring up a stone cast. Hydrophilic materials appear to facilitate the casting of the impressions with stone. The automixing devices seem to provide convenience without sacrificing the quality of the impression and are currently available for several products. As with all elastomeric impression materials, proper handling is necessary to ensure the best results. The vinyl polysiloxanes seem to be an excellent choice of impression materials for many clinical situations. PMID- 2186078 TI - Position of the American Dietetic Association: very-low-calorie weight loss diets. AB - It has been well documented that a VLCD can produce large and rapid weight loss. A number of studies using appropriate levels of high biologic value protein, vitamin and mineral supplementation, and careful monitoring have shown that the VLCD can be safe. Careful monitoring by a physician experienced in such programs and by a registered dietitian is essential. The maintenance of weight loss must be of key importance throughout the program, necessitating the skills of a multidisciplinary team with medical, nutritional, and behavioral training. It must be recognized that the VLCD is only one part of a total weight management program. The complete program is needed for long-term success. Insurance reimbursement for the services of all members of the health care team, including dietitians, facilitates and supports the multidisciplinary team approach. Potential candidates for this program and health professionals must realize that VLCDs are not for everyone and can be harmful for persons who do not meet the following selection criteria: (a) at least 30% overweight, with a minimum body mass index of 32. (b) free from contraindicated medical conditions: pregnancy or lactation, active cancer, hepatic disease, renal failure, active cardiac dysfunction, or severe psychological disturbances. (c) committed to establishing new eating and life-style behaviors that will assist the maintenance of weight loss. (d) committed to taking the time to complete both the treatment and the maintenance components of a program. Dieters must receive careful medical and nutritional monitoring throughout the program and should continue with nutrition, exercise, and behavioral counseling after cessation of the VLCD until sound eating and life-style habits can be established. The length of time an individual is on the VLCD must be carefully monitored and the VLCD discontinued immediately if medical tests and/or weight loss indicate increased health risks to the client. Finally, potential clients must be adequately warned that there are limitations and risks involved with the VLCD. A VLCD is no magic cure. It requires considerable effort and commitment on the part of both practitioners and participants to ensure the program's success. PMID- 2186079 TI - Calcitonin therapy in osteoporotic syndromes. PMID- 2186080 TI - Calcium intake and bone health throughout life. AB - Calcium requirement varies with stage of growth, with physiological drains (eg, pregnancy and lactation), and with factors that influence absorption and excretory loss (eg, gonadal hormone status and sodium and protein intakes). While for certain life-stages the cited requirement values are higher than currently recommended, they are below the intakes of both contemporary hunter-gatherers and our closest primate relatives, after adjusting for body size. Hence, they can be considered high only in comparison with current US practices. However, it also needs to be emphasized that bone health is a multifactorial affair and that meeting calcium requirements alone will neither guarantee optimal bone growth nor protect against bone loss if other critical factors are missing. For example, calcium affords only minimal protection against either immobilization or estrogen withdrawal bone loss. Thus, while assuring an adequate calcium intake remains a sound strategy, it cannot be considered a panacea. PMID- 2186081 TI - Physical exercise and bone health. PMID- 2186082 TI - An analysis of contact lens enzyme cleaners. AB - Currently, in the United States, the Food and Drug Administration has approved a number of enzyme cleaners for use with soft contact lenses. These cleaners contain three active enzymes--papain, pancreatin, and subtilisin. Although several studies have compared the cleaning efficacy of papain and pancreatin, little information exists concerning subtilisin. It was the aim of this investigation to compare the performances of four marketed enzyme cleaners, including Allergan Enzymatic (papain), Optizyme (pancreatin), ReNu Effervescent (subtilisin), and Ultrazyme (subtilisin A). Lenses were examined using the scanning electron microscope, and the amount of deposits on the lens surfaces quantified by digital analysis. All of the enzyme cleaners were effective in removing deposits from the contact lenses surfaces, but there was no significant difference in the cleaning efficacy of the four cleaners tested. PMID- 2186083 TI - Legal consequences of the FDA's 7-day extended wear letter. AB - The U.S. Food and Drug Administration (FDA) recently sent contact lens practitioners a letter advising them that the FDA had asked manufacturers to indicate a maximum recommended wearing time of 7 days for cosmetic extended wear soft contact lenses. This paper discusses the authority of the FDA and the legal consequences of the FDA's "7-day Letter." Congress has authorized the FDA to enact rules, guidelines and recommendations. The 7-day letter does not appear to be any of the above. However, it does have a significant effect on contact lens practitioners' professional responsibilities and legal obligations because the letter has led to changes in product labeling and the standard of care for extended wear patients. Practitioners would be wise to give careful consideration to any deviation from the FDA's recommendation and the provisions of the product labeling. As any deviation will likely impose greater legal responsibility on the practitioner, the special circumstances that justify the deviation should be thoroughly documented in an informed consent agreement. PMID- 2186084 TI - An experimental system for the molecular analysis of the aging process: the budding yeast Saccharomyces cerevisiae. PMID- 2186085 TI - The implications of the acquired immunodeficiency syndrome for gerontology research and geriatric medicine. PMID- 2186086 TI - Tissue and cellular distribution of alpha-L-iduronidase in the pig. AB - We investigated the alpha-L-iduronidase activity of various pig tissues. Furthermore, we examined the tissues using antibody, enzyme immunoassay (EIA), and immunohistochemical methods. The amounts of enzyme measured by the EIA method in the various tissues were proportional to their enzyme activities and also to their immunohistochemical characteristics. The tissues could thus be classified into three groups: a high enzyme activity group composed of the liver, kidney, and spleen; a moderate activity group comprising the lung, lymph nodes, stomach, ileum, colon, and pancreas; and a low activity group consisting of the heart, diaphragm, iliopsoas muscle, cerebrum, cerebellum, and skin. The molecular weight of the enzyme in each tissue did not reveal any heterogeneity, having two components of 70 KD and 62 KD by Western blot analysis. Immunohistochemically, alpha-L-iduronidase was strongly detected in the lysosomal membranes of cells of the mononuclear phagocyte system, epithelial cells of the proximal tubules in the kidney, and some blastic cells, whereas hepatocytes revealed weak positive reactions. The tissue and cellular distribution of the enzyme appeared to have a close relation to tissues that manifest or are affected by alpha-L-iduronidase deficiency. PMID- 2186088 TI - Cytochemical localization of mercury in Saccharomyces cerevisiae treated with mercuric chloride. AB - We describe a cytochemical method for localizing mercury at the electron microscopic level in the yeast Saccharomyces cerevisiae. After addition of a lethal concentration of mercuric chloride to growing yeast cells, mercury was associated with the cell wall and cytoplasmic membrane. Little or no mercury was present in the cytoplasm. Electron probe X-ray microanalysis (EPMA) confirmed that the cytochemical reaction, visualized as mercury-silver complexes, was localized in dense bodies consisting of a core of mercury sulfide polymers surrounded by a shell of silver atoms. PMID- 2186087 TI - Light and electron microscopic immunocytochemical analysis of antibodies directed against GnRH and its precursor in hypothalamic neurons. AB - A battery of antibodies directed against different portions of the precursor to gonadotropin-releasing hormone (GnRH), as well as to the mature decapeptide, were characterized immunocytochemically in two ways. Absorption experiments were used to determine the epitope recognized by each antiserum. Electron microscopic immunocytochemistry was then used to define the subcellular organelles that contained reaction product when tissue was incubated with these reagents. These latter observations helped to determine if the antibody recognized the epitope as part of the intact precursor or only after it had been cleaved from parent protein. Our results demonstrate that the GnRH precursor is routed from the rough endoplasmic reticulum through the Golgi apparatus to the secretory vesicles. Furthermore, we show that initial cleavage and processing of the GnRH precursor begin in the cell soma. These antibodies should be useful in the future in determining changes in processing of precursor in animals that differ in endocrine function. PMID- 2186089 TI - Insulin and insulin mRNA are detected in neuronal cell cultures maintained in an insulin-free/serum-free medium. AB - We investigated the effect of a serum-containing medium, exogenous insulin, and insulin-free/serum-free media in the regulation of the rabbit brain insulin-like peptide (ILP) in neuronal cell cultures. The presence of serum or insulin in the medium resulted in approximately 3-5% of neurons that were positive for the peptide by immunohistochemistry and for insulin mRNA by in situ hybridization. The absence of insulin in the medium resulted in a three- to fourfold increase (p less than 0.001) in the insulin-immunoreactive and insulin mRNA-containing neurons. Additionally, in the presence of exogenous insulin or serum, the amount of insulin present in the medium, as measured by ELISA, decreased with time (approximately 80%), the former slower than the latter when compared with their respective zero time point values. However, an increase (approximately 80% from zero time) was noted in the absence of insulin or serum, and this lasted for 24 48 hours alone. The presence of an increased insulin/ILP content in the medium and the increase in the numbers of insulin-immunoreactive neurons suggests an important role of the peptide in the brain. The observation of increased synthesis and secretion of neuronal ILP in the absence of insulin is indicative of an autocrine effect of exogenous insulin on neuronal production of ILP, which in turn may be important in the growth and maintenance of neuronal and possibly glial cells. PMID- 2186091 TI - Trimalleolar ankle fractures and open ankle fractures. PMID- 2186090 TI - Immunolocalization of transferrin and transferrin receptor in mouse small intestinal absorptive cells. AB - The mechanisms by which the duodenal mucosa absorbs iron are unknown. Insorption into absorptive cells of luminal iron bound to transferrin via receptor-mediated endocytosis has been hypothesized, but transferrin and transferrin receptor are absent in apical microvillous brush borders of small bowel biopsies taken from fasted patients and normal volunteers. We hypothesized that a normal iron containing diet might induce the transient appearance of transferrin and transferrin receptor in apical brush borders of small intestinal absorptive cells in a normal mouse that was provided iron-containing chow until the moment of sacrifice. Light and electron microscopic immunolocalization of transferrin and transferrin receptor in proximal small intestinal absorptive cells was limited to basolateral membranes and coated pits of cells predominantly in the crypts and basal regions of the villi. Transferrin and transferrin receptor were not detected in apical microvillous brush border membranes of these enterocytes. In parallel immunolocalization protocols designed to show the ability to immunodetect other antigens at these locations, maltase and proteoglycan were demonstrated in apical microvillous brush border membranes and in basolateral membranes, respectively, in absorptive cells of small intestinal villous tip, base, and crypt regions. Furthermore, transferrin and transferrin receptor were immunolocalized in hepatocyte sinusoidal microvillus membranes. We conclude that food does not induce the appearance of immunodetectable transferrin and transferrin receptor in the apical microvilli of small intestinal absorptive cells and, therefore, that these iron transport proteins are not involved in the apical microvillous membrane transport of luminal dietary iron. PMID- 2186092 TI - Open fractures of the ankle joint. PMID- 2186093 TI - Fractures of the forefoot. AB - In conclusion, the principles of fracture management recommended for treatment of musculoskeletal injuries elsewhere should be applied to the forefoot. Anatomic reduction, adequate fixation, and meticulous soft-tissue management will provide optimum functional recovery. PMID- 2186094 TI - The treatment of tarsometatarsal fracture-dislocation. PMID- 2186095 TI - Fractures of the talus. PMID- 2186096 TI - Hallux rigidus. PMID- 2186097 TI - Subtalar dislocations. PMID- 2186098 TI - Surgical management of calcaneus fractures: indications and techniques. PMID- 2186099 TI - Tibial pilon fractures. AB - The character of soft-tissue and bony injury in tibial pilon fractures varies widely, and no one treatment method is right for all. Surgery is undertaken to reduce the fibula, to restore length, to align the articular surface, to stabilize the fracture, and to obtain coverage without tension. If bone grafting is required, it should be done as early as possible. Complications, which occur frequently, must be aggressively managed. PMID- 2186100 TI - Factors influencing the choice of external fixation for distraction osteogenesis. PMID- 2186101 TI - Treatment of tibial nonunion and bone loss with the Ilizarov technique. PMID- 2186102 TI - External fixation of the femur. AB - External fixation of the femur remains a viable option in the acute treatment of fractures or in reconstructive procedures. As in any method of fixation, the surgeon must be familiar with the device used, the mechanical properties of the device, the application technique of such devices, and, most importantly, the postoperative management of the patient. PMID- 2186103 TI - External fixation in children: lower extremity. PMID- 2186104 TI - External fixation in the upper extremity. PMID- 2186105 TI - Complications of pin and wire external fixation. PMID- 2186106 TI - External fixation in the multiply injured patient. PMID- 2186107 TI - Sesamoid pain: causes and surgical treatment. PMID- 2186108 TI - Choosing upper-limb fracture fixation. PMID- 2186109 TI - Open fractures and wound management. PMID- 2186110 TI - Hand fractures. PMID- 2186111 TI - Comminuted fractures of the distal radius. PMID- 2186112 TI - Complex upper-extremity fractures. AB - Complex proximal humeral fractures are a challenge to the orthopaedic surgeon. Achieving fracture healing while avoiding loss of function is best accomplished by early rigid fixation or prosthetic replacement, depending on the fracture type and characteristics. PMID- 2186113 TI - Complex fractures about the elbow. PMID- 2186114 TI - Wrist and forearm reconstructive procedures after complex upper-extremity trauma. PMID- 2186115 TI - The management of nonunions of the humerus. PMID- 2186116 TI - An overview of normal walking. PMID- 2186117 TI - Decision-making in bunion surgery. PMID- 2186118 TI - Gait analysis in sports medicine. PMID- 2186119 TI - Pathologic gait. AB - The diagnosis of gait deviations and their causes requires three levels of knowledge. First is an awareness of the functional limitations caused by each type of abnormality (contracture, muscle weakness, pain, and spasticity). Second is familiarity with normal function. Third is having a trained eye or gait analysis system that is capable of identifying the gait deviations. Once diagnosis is complete, a fourth requirement is the ability to use the findings to set up an appropriate treatment regimen. PMID- 2186120 TI - Gait analysis in neuromuscular disease. PMID- 2186122 TI - The orthopaedist as prosthetic team leader: getting the best for your patient from the team. AB - In summary, care of the amputee is an ongoing process, from evaluation and treatment of the initial disease or traumatic event, through fabrication and fitting of the prosthesis, to the amputee's return to as normal a lifestyle as possible. It is a process that has evolved over the years into a distinct approach designed to get the best for the patient from the team. PMID- 2186121 TI - Evaluation of surgical procedures and/or joint implants with gait analysis. PMID- 2186123 TI - Surgical techniques for conserving tissue and function in lower-limb amputation for trauma, infection, and vascular disease. AB - Certain factors regarding amputation level, such as the level of traumatic amputation, the position of a malignant tumor in a limb, or the level to which gangrene has progressed, cannot be changed. More important, in this regard, is the attitude of the surgeon toward amputation. This attitude determines the care with which the final level is selected, the manner in which the amputation is performed, and the way in which postoperative management, including prosthetic care, is handled. To achieve the desired long-term result for the amputee, the surgeon should view amputation as a reconstructive procedure rather than a destructive one, should be willing to do staged procedures to preserve potentially functional tissue, should be ready to consider and plan innovative surgical approaches, and should keep abreast of prosthetic advances as they affect surgical technique and postoperative management. PMID- 2186124 TI - New concepts in lower-limb amputation and prosthetic management. PMID- 2186125 TI - Overview of prosthetic feet. PMID- 2186126 TI - Etiology and treatment of the bunionette deformity. PMID- 2186127 TI - Current concepts in above-knee socket design. AB - To review the fundamental tenets of above-knee socket design proposed by Radcliffe nearly 40 years ago, sockets must be designed to achieve vertical support of body weight, stabilization of the residual skeleton in both the coronal and sagittal planes, accommodation of functioning muscles, voluntary control of the prosthetic knee, individualized design, and an optimum balance of comfort, function, and appearance, both statically and dynamically. Contemporary approaches represent enhancements and refinements toward these ends, but each of these fundamental goals must be satisfied no matter what socket design is selected. PMID- 2186128 TI - Orthopaedic aspects of skeletal dysplasias. PMID- 2186129 TI - Lower-extremity abnormalities in dwarfing conditions. PMID- 2186130 TI - Spinal deformity in short-stature syndromes. AB - Although almost any spinal deformity can occur in any skeletal dysplasia, there are specific spinal problems in each disorder that require periodic assessment and a particular awareness. Atlantoaxial instability frequently accompanies spondyloepiphyseal dysplasia congenita and Morquio's syndrome. Severe progressive kyphoscoliosis is found in diastrophic dysplasia. Although scoliosis can be found in many of these syndromes to some degree, it is very rare in achondroplasia. The most common deformity found in skeletal dysplasias as a whole seems to be kyphosis: cervical kyphosis in diastrophic dysplasia and thoracolumbar kyphosis in achondroplasia, pseudoachondroplasia, and many of the short-stature syndromes of metabolic etiology. Spinal stenosis is extremely common in achondroplasia, both at the lumbar and cervical areas. It is important to establish the correct diagnosis early so that the orthopaedist is able to focus on the areas at highest risk of developing spinal problems, and proceed with efficacious and timely treatment. PMID- 2186131 TI - Thromboembolic disease after total knee surgery: a critical review. AB - Thromboembolic disease represents a major threat to our patients after total knee surgery. At present, the significance of calf and thigh thrombi is undetermined, the incidence of pulmonary embolism is poorly defined, and the best regimens for prophylaxis and therapy are not yet finalized. Continued open-minded investigation will be needed to resolve these problems. PMID- 2186132 TI - Advances in prevention of venous thromboembolic disease after elective hip surgery. PMID- 2186133 TI - Blood conservation techniques in orthopaedic surgery. AB - In summary, reduction of blood loss and coincidental decrease in the number of blood transfusions is now of paramount importance in orthopaedic surgery. Methods to reduce blood loss include preoperative planning, hypotensive anesthesia, and meticulous surgical technique. If transfusion is necessary, autologous replacement is always preferable. Overall, the goals in blood conservation in surgery are first to decrease the amount of blood lost, and second to be sensible in replacement of this loss. PMID- 2186134 TI - Blood products: optimal use, conservation, and safety. AB - A review of our experience in total joint arthroplasty revealed that the cell saver was not cost-effective in the case of routine primary hip or knee replacement. Its use should be restricted to cases of revision hip and knee surgery in which infection has been ruled out. Preoperative aspiration remains the most reliable method for accomplishing this. However, if the aspiration is negative and the intra-articular fluid obtained at the time of surgery is suspicious for infection, either in appearance or on Gram stain or cell count, it is best to abandon use of the cell saver. Predonation should be routine for all hip replacement cases unless there are specific contraindications. In general, there is good acceptance of this program by patients, although a few have specifically indicated they would prefer to run the risk of homologous transfusion. Two units available for primary replacement are more than ample. In cases of revisions, a first revision justifies a minimum of 3 units. For complex revision cases involving patients with three or more previous procedures on the hip, or those requiring significant bone resection or large segment grafting, the maximum possible number of units should be obtained. Autologous blood reinfusion should be done for essentially the same indications as homologous transfusion even though risks are sharply reduced. The local source for autologous collection will then follow its own specific protocol for the disposition of remaining units. In every case, the surgical technique should be careful and directed toward limiting intraoperative blood loss. PMID- 2186135 TI - The technique of total shoulder arthroplasty. PMID- 2186136 TI - Total shoulder arthroplasty: complications and revision surgery. AB - Fortunately, revision surgery after prosthetic shoulder arthroplasty is rarely required. However, various complications or combinations of complications can lead to the need for revision surgery. For many of these, several treatment options are possible. Recognizing all the problems that contributed to failure in an individual patient may be difficult before revision surgery. Understanding the abnormality present at the time of surgery requires considerable experience. For example, glenoid loosening, in addition to being accompanied by scapular bone loss, may be associated with rotator-cuff tearing, instability, or joint contracture. In addition to the component loosening, all of these must also be treated if the revision procedure is to be successful. When addressing glenoid loosening, it seems to be best to revise the component, if possible. If there is extreme bone loss, one may have to bone graft the deficiencies and not replace the glenoid component. Fortunately, clinically significant humeral loosening is rare. When it occurs, revision of the component is justified and almost always possible. In hemiarthroplasties with pain, conversion to a total shoulder arthroplasty by placing a glenoid component is highly effective. In instability after shoulder arthroplasty, soft-tissue repair does not always create stability. Unfortunately, for most patients, component revision is a necessary part of the revision surgery. When rotator-cuff tearing is acute, repair is indicated; for chronic rotator-cuff tearing, repair depends on the severity of the symptoms. When infection develops after shoulder arthroplasty, implant removal is almost always necessary, but occasionally, in low-grade infections, a primary or secondary exchange procedure may be possible. PMID- 2186137 TI - Molecular mechanisms in musculoskeletal sepsis: the race for the surface. PMID- 2186138 TI - Management of soft-tissue wounds associated with open fractures. PMID- 2186139 TI - Antibiotic management of open fractures. PMID- 2186140 TI - Surgical arthrodesis techniques for foot and ankle pathology. PMID- 2186141 TI - Clostridial myonecrosis. AB - The best treatment for gas gangrene is prevention by following the principles of thorough debridement, immediate effective parenteral antibiotic therapy, and delayed closure of open fractures. PMID- 2186142 TI - Chronic osteomyelitis: results of treatment. AB - As stated previously, approximately 8% of the patients evaluated do not require curative treatment and palliative treatment with suppressive therapy may be successful (Fig 2). For the most part, these are C-hosts for whom the morbidity of treatment is greater than the morbidity of disease or exceeds the expected gain. The overall spectrum of treatment in 411 of my patients (1983-1988) is seen in Table 5. Of the 411 patients, 228 (55%) required a bone graft; of these, 42% were primary grafts. Soft-tissue reconstructions were required in 37% of the entire patient population and in 59% of the type IV lesions. The overall amputation rate was 9%. There were no statistical differences in success rates between stable and unstable lesions, nor when cases were stratified for the type or number of bacteria present. However, compromised patients had a statistically inferior prognosis compared with patients who had normal physiologic profiles (Outline 1). PMID- 2186143 TI - The use of septopal (polymethylmethacrylate beads with gentamicin) in the treatment of chronic osteomyelitis. PMID- 2186144 TI - Spinal infections. PMID- 2186145 TI - Infections of the hand. Introduction and overview. PMID- 2186146 TI - Treating infections of the hand: identifying the organism and choosing the antibiotic. PMID- 2186147 TI - Selected acute infections. PMID- 2186148 TI - Chronic infections. AB - The surgeon is rarely the first physician to examine the hand with a chronic infection. In most cases, simple treatment has been tried and has failed. The surgeon must think of atypical mycobacteria and fungi and then systematically make a diagnosis by biopsy and culture and by excluding other diseases and conditions. Because these infections can be very damaging to the hand or wrist, treatment should be rendered promptly and adequately. These general principles are no different from those followed in treating acute hand infections or actually for any disease. PMID- 2186149 TI - Initial management of the patient with multiple injuries. PMID- 2186150 TI - Management of fractures of the femur, tibia, and upper extremity in the multiply injured patient. PMID- 2186151 TI - Evaluation and treatment of trauma to the vertebral column. PMID- 2186152 TI - Fractures of the pelvic ring and acetabulum in patients with severe polytrauma. PMID- 2186153 TI - Hindfoot arthrodeses. AB - In summary then, pain is the primary indication for a hindfoot arthrodesis procedure. Arthrodesis is performed only on those joints that show degeneration or significant deformity. Finally, the technique described uses a moldable bone graft. This technique is applicable both for an isolated talocalcaneal joint arthrodesis and for triple arthrodeses. PMID- 2186154 TI - The pathogenesis and treatment of ankle fractures: historical studies. PMID- 2186155 TI - The pathogenesis and treatment of ankle fractures: classification. PMID- 2186156 TI - The pathogenesis and treatment of bimalleolar ankle fractures. PMID- 2186157 TI - Ankle fractures with diastasis. PMID- 2186158 TI - [Studies on Chlamydia pneumoniae, strain TWAR, infection. I. Experimental infection of C. pneumoniae in mice and serum antibodies against TWAR by MFA]. AB - Six to seven-week-old ICR mice were inoculated intranasally with C. pneumoniae TW 183 strain and observed for sickness and death. The inoculated mice showed weakness within the 1st day and decrease in weight were observed, however, mice were cured within 7 days after inoculation. No death was observed. Histopathological studies of the mice lungs clearly revealed interstitial pneumonitis on the 3rd day and parenchymal pneumoniae on the 5th day after inoculation. Pathological changes were, however, improved in 10 to 14 days after inoculation. Inclusions were detected from the 1st to 10th day in broncho epithelial cells and alveolar epithelial cells by DFA stain and TWAR specific monoclonal antibody. Serum antibodies, IgG and IgM, were assayed by microplate immunofluorescence antibody technique (MFA). From 7 to 14 days after inoculation, the titer of IgG rapidly increased and reached 1:4096 and then this titer level was maintained for 3 weeks and more. On the other hand, IgM was detected on 7th day and increased up to 1:16 on 14th day. However, the IgM titer declined within 1 month. To examine the specificity of the antibody titration, IgG in sera prepared against C. pneumoniae TW-183, C. psittaci Cal 10 and C. trachomatis L2 strains were assayed by MFA using in situ inclusions of each strain and compared. The results indicated that IgG titer in homologous combination between antigen and antiserum was always 2 times higher than that of heterologous combination, suggesting strongly that the chlamydial species responsible for the infection could be differentiated by the comparison of IgG titers obtained in the MFA titration. PMID- 2186159 TI - [Therapeutic evaluation of combination therapy using C-425, human native immunoglobulin liquid preparation for i.v. administration, with antibiotics in severe infections in the field of internal medicine]. AB - A novel human native immunoglobulin liquid preparation for intravenous injection, C-425, was used in combination with antibiotics to study its efficacy, safety, and usefulness in 262 patients with severe infections which had not responded to antibiotic therapy of 3-day or more duration. As a result of the Committee judgement, 12 of the 262 patients were excluded from this study; 87 were included only in safety analysis; 163 (62.2%) were included in efficacy, safety, and usefulness analyses (complete inclusion). The complete analysis of 163 patients consisted of 93 patients (57.1%) with suspected septicemia, 33 (20.2%) with pneumonia, and 18 (11.0%) with septicemia. Eighty percent or more of the patients had severe underlying diseases such as leukemia and malignant lymphoma. Clinical efficacy of C-425 was judged by the doctors in charge to be "excellent" or "good" in 49.1% of the total cases. The rate of effectiveness was calculated at 74.8% when "excellent", "good" and "fair" cases were all included. Similarly, the rate of effectiveness calculated from the results of Committee judgment was 53.4% when "excellent" and "good" cases were included, and 68.7% when "excellent", "good" and "fair" cases were included. Microbiological assessment was conducted in 19 patients. Causative organisms were eliminated in 11 patients, decreased in number in 1, persisted in 5, and replaced in 2. The rate of elimination was 57.9%. Side effects appeared in 6 of 250 patients (2.4%). It was judged that 3 patients (1.2%) of the 6 were affected by the drug or suspected to be affected, but they were not considered clinically important. Hepatic disfunction was found in 4 patients (1.6%) of the 250; but it was not clarified whether this was related to the drug. From these results, C-425 was considered to be an effective and very safe drug for treating severe internal infections. PMID- 2186160 TI - [Therapeutic evaluation of combination therapy using C-425, human native immunoglobulin liquid preparation for i.v. administration, and antibiotics in severe and/or refractory infections in pediatrics]. AB - A newly developed human immunoglobulin liquid preparation for intravenous injection was studied for efficacy, safety, and usefulness in treating severe and/or refractory infections in children receiving antibiotic treatment. It is suggested that C-425 is a useful intravenous preparation of human immunoglobulin for the treatment of severe and/or refractory infections in pediatrics. C-425 was administered to 87 inpatients with severe and/or refractory infections at 23 institutions nationwide. The Committee selected 61 cases for the present analysis. Physicians in charge judged clinical efficacy of C-425 to be "excellent" in 23 cases (40.4%), "good" in 24 (42.1%), "fair" in 7 (12.3%), "poor" in 3 (5.3%), and "unknown" in 4. The efficacy rate was calculated at 82.5% when the "excellent" and "good" cases were combined, and 94.7% when the "fair" cases were also included. According to the Committee's judgement, the efficacy of C-425 was "excellent" in 27 cases (44.3%), "good" in 18 (29.5%), "fair" in 7 (11.5%), and "poor" in 9 (14.8%). The efficacy rate was 73.8% when the "excellent" and "good" cases were combined. The rate increased to 85.2% when the "fair" cases were added. Organisms were identified in 31 cases, and the time course was followed in 19 instances. Organisms were eliminated in 12 cases (63.2%), decreased in number in 2 (10.5%), and persisted in 5 (26.3%). Eradication rate was 63.2%. One of the 87 patients died of fulminant hepatitis 2 days after the end of the treatment. The remaining 86 cases were analyzed for the safety of C-425. A skin rash was observed in one case. Laboratory examination revealed increase in transaminase levels in a total of 8 cases; both in GOT and GPT in 5, in GOT alone in 2, and in GPT alone in 1. These findings were not clinically important. PMID- 2186161 TI - [Therapeutic evaluation of combination therapy using C-425, human native immunoglobulin liquid preparation for i.v. administration, with antibiotics in severe infections in the field of surgery]. AB - In a nationwide study conducted in 11 surgical institutions of C-425, a newly developed human native immunoglobulin liquid preparation for intravenous injection, was combined with conventional antibiotic treatment to investigate the efficacy and safety. A total of 47 patients with severe infections which had not symptomatically responded to 3-day or longer treatment with any antibiotics was included. Doctors in charge judged the efficacy of C-425 to be "excellent" in 3 patients, "good" in 13, "fair" in 15, and "poor" in 4. Thus, a total of 16 patients (45.7%) was judged to have responded to C-425 when the "excellent" and "good" responses were combined. The number responding was 31 (88.6%) when the "fair" cases were also included. Excluding 31 patients who did not meet the Committee's criteria, the Committee judged the efficacy of C-425 in a total of 16 patients; the efficacy was "excellent" in 2 patients, "good" in 4, "fair" in 9, and "poor" in 1. The number of responding patients was 6 (37.5%) of the 16 when the "excellent" and "good" cases were combined, and 15 (93.8%) when the "fair" cases were added. Bacteriological assessment was conducted in a total of 9 patients. Causative bacteria were eradicated in 3 patients, decreased in number in 1, replaced in 2, and persisted in 3. Thus, bacteriological efficacy was observed in 6 of the 9 patients (66.7%). Neither adverse reactions nor drug related laboratory abnormalities were observed in the 47 patients. PMID- 2186162 TI - Secretion of mucoid material by lymphokine-activated killer cells: study by light and electron microscopy. AB - When lymph node cells from nude mice were grown on embryonic fibroblast monolayers together with rat interleukin-2, only one type of colonies developed. These colonies were composed of cytotoxic cells termed "granular/lymphokine activated killer/mucus-secreting cells" (LAK-GM). An extensive differentiation course, in which all the cellular components were involved, ended with a population of short-lived, mature, nondividing large cells that apparently synthesized and deposited a flowing mucoid material (FMM) that stained distinctly blue with periodic acid-Schiff/alcian blue (PAS-Ab) at pH 1 and distinctly red by the naphthol AS-D-chloracetate method for specific esterase. So far, the best monolayers to trigger the FMM synthesis were those prepared from 16- to 18-day old whole embryos. These cells were compared with LAK cells that developed on monolayers (such as embryonic skin or adult kidney) that did not trigger FMM synthesis. They were also compared with other cell types that differentiated in colonies on the fibroblast monolayers: histiocytes (fixed macrophages), mixed granulocytes/monocytes, mucosal mast cells; and with populations of mature rat T killer cells developed on same mouse monolayers. Features distinctive to the secreting LAK-GM cells were presence of masses of membrane-limited vesicles that were strictly confined to the surface of the cells in FMM-containing colonies. All transitional forms of budding activity could be seen on the cell surface facing the masses. Within the same cells, many granules displayed varying degrees of degradation, the granular material being transformed into flocculent material that formed small pools facing each degraded surface. Other characteristics of the LAK-GM lineage were the accumulation of glycogen prior to the appearance of the FMM, the presence of several structures of a ribosome-lamella complex in the LAK-GM in colonies that did not accumulate FMM, and filopodia commonly emerging from the pole proximal to the nucleus. Of various fixation methods tried, only after treatment with absolute alcohol and subsequent drying was the FMM stained with PAS-Ab. By subsequent wetting, the capacity to be stained was irreversibly lost. After incubation of the living cultures with the enzymes hyaluronidase or chondroitinases AC or ABC, the FMM disappeared. These observations suggest a triggering mechanism by the embryonic mesenchymal fibroblastoid cells for synthesis and secretion of mucous material that is a proteoglycan of the chondroitin sulfate group. PMID- 2186163 TI - Fibrocartilaginous emboli to the spinal cord: a review of the literature. AB - Fibrocartilaginous emboli to spinal cord vessels is an apparently rare cause of spinal cord injury. A review of the medical literature reveals only 24 reported cases, none of which were noted prior to 1961. The authors have reviewed an additional, but as yet unpublished, case. The majority of patients presented with the acute onset of pain located around the vertebral column which was followed by progressive paresis/paralysis and respiratory insufficiency. Minor trauma to the vertebrae prior to onset was noted in most cases. The time to maximum neurologic deficit (typically paraplegia or quadriplegia) ranged from minutes to 24 to 48 hours. In all but one case the spinal cord injury resulted in death within 11 months of onset with a median of 2.5 to 4 months. One patient lived six years and seven months with respiratory support. In yet another case, a fibrocartilaginous embolus to a sacral nerve root was found as an incidental finding at autopsy. The incidence of both asymptomatic and clinically significant emboli may be more common and depends on the awareness of the medical community to consider this in the differential diagnosis of spinal cord injury. PMID- 2186164 TI - Beyond positive thinking. AB - Fast-paced change and turmoil can make us lose sight of the power of positive thinking. Eric Olsen's two briefs illustrate characteristics of executives who became healthier in chaotic times and how the mind can be trained for success. PMID- 2186165 TI - Hypnotics and occupational medicine. AB - The appropriate use of hypnotics requires an understanding of the nature of the patient's insomnia and lifestyle. In the context of occupational medicine, the potential effects of these drugs on job skills and the persistence of such effects are also important considerations. This report reviews the factors that must be considered in the investigation of impaired performance due to hypnotics and the pharmacokinetic properties that determine the persistence of action of these drugs. Sleep disturbance associated with transmeridian flights (jet lag) is used to illustrate the place of hypnotics in the management of a transient form of insomnia. PMID- 2186166 TI - Medication-induced performance decrements: cardiovascular medications. AB - Clinicians may not give complete consideration to the occupational and recreational impact that prescribed medications can have on patients. Because cardiovascular disease is a major health problem that affects a large segment of the adult population in the United States, a significant portion of the adult work force may be expected to be under treatment with cardiovascular medications. Many may experience decrements in job performance as a result of such therapy. This article discusses the incidence and impact of occupationally relevant side effects of several categories of cardiovascular drugs, including beta blockers, calcium channel blockers, antiarrhythmics, vasodilators, nitrates, lipid-lowering agents, and diuretics. PMID- 2186167 TI - Psychotropic medications and work performance. AB - The drug classes used to treat the major psychiatric disorders--antidepressants, antimanic agents, antipanic drugs, and neuroleptics--all produce side effects that may affect work performance. An understanding of the pharmacology of psychotropic drugs will enable the clinician to recognize the most common adverse effects of these drugs on performance. For example, tertiary amine tricyclic antidepressants and benzodiazepines may decrease alertness. The slowed visual accommodation produced by amine tricyclics or low-potency neuroleptics may adversely affect fine-motor control. Likewise, various psychotropic drugs, including neuroleptics and lithium (at toxic levels), may cause motor incoordination. However, the clinician should bear in mind that failure to provide treatment for psychiatric disorders is far more disruptive than are any side effects of such treatment. PMID- 2186168 TI - Oral contraception for women in their 40s. PMID- 2186169 TI - Electrogenic properties of the Na:Ca exchange. PMID- 2186170 TI - A rapid microassay for hemolytic antibody--its application to immunotoxicological study. AB - A rapid microassay for hemolytic antibody using an automatic spectrophotometer was developed. This microassay was parallel to hemolytic plaque forming cell (PFC) assay most commonly used to detect antibody formation. The former had more advantages than the latter did. The data obtained using arsenic and some metallic compounds as immunomodifiers suggested that this microassay was suitable for the screening of immunomodifiers in immunotoxicological and immunopharmacological studies which deal with a large number of samples within limited time. PMID- 2186171 TI - The extra-auditory effects of noise and annoyance: an overview of research. AB - This paper is an overview of research on the extra-auditory effects of exposure to noise. The aim is to demonstrate the pervasiveness of the effects in support of noise reduction at the source for reasons that go well beyond hearing conservation. The areas discussed are performance effects, including vigilance, selective attention, sensory-motor behavior and memory; physical effects, including cardiovascular disease and sleep-related disorders, and annoyance, with special reference to psychological outcomes. The results show that high levels of noise are particularly disruptive for dual-task paradigms, requiring attention sharing, and sequential responding, involving speed and accuracy. Both the level and the type of noise background affect memory, severely limiting the number of stimulus dimensions that may be simultaneously encoded and retained. Community noise with a preponderance of heavy traffic and aircraft flyovers affects sleep, resulting in changes in the normal pattern of EEG fluctuations, and increases in movement and heart rate. Lastly, noise causes annoyance, with its own set of by products: job dissatisfaction, irritability and anxiety over potential risk. PMID- 2186172 TI - A novel human immunodeficiency virus type 1 protein, tev, shares sequences with tat, env, and rev proteins. AB - We have characterized a novel 28-kilodalton protein, p28tev, detected in human immunodeficiency virus type 1-infected cells. tev is recognized by both tat and rev monospecific antibodies. tev is initiated at the tat AUG and contains the first exon of tat at its amino terminus, a small portion of env in the middle, and the second exon of rev at its carboxy terminus. A cDNA clone producing tev was cloned and expressed in human cells. Sequence analysis revealed that the tev mRNA is generated by splicing to a novel exon located in the env region. This identifies a fourth class of multiply spliced human immunodeficiency virus mRNAs, produced in infected and transfected cells. tev is regulated during the virus life cycle similarly to the other regulatory proteins, tat, rev, and nef, and displays both tat and rev activities in functional assays. Since tev contains important functional domains of tat and rev and is produced very early after transfection, it may be an important regulator in the initial phase of virus expression. Another rev-related protein, p18(6)Drev, containing env and rev sequences, was characterized and was found not to have detectable rev activity. PMID- 2186173 TI - The cauliflower mosaic virus open reading frame VII product can be expressed in Saccharomyces cerevisiae but is not detected in infected plants. AB - Antiserum was prepared against a synthetic peptide corresponding to the N terminal 20 amino acids of the protein encoded by cauliflower mosaic virus (CaMV) open reading frame VII (ORF VII). This antiserum was used to detect the expression of CaMV ORF VII either in Saccharomyces cerevisiae transformed by an expression vector containing CaMV ORF VII or in CaMV-infected plants. Only in S. cerevisiae has a 14-kilodalton protein been detected. PMID- 2186174 TI - Spleen necrosis virus gag polyprotein is necessary for particle assembly and release but not for proteolytic processing. AB - The nature of spleen necrosis virus pol gene expression and the role of gag and gag-pol polyproteins in virion assembly was investigated. The DNA sequence of the gag-pol junction revealed that the two genes occupy the same open reading frame but are separated by an in-frame amber stop codon. Biochemical analysis of gag pol translational readthrough in vitro and in Escherichia coli suggests that, in a manner similar to that in other mammalian type C retroviruses, amber stop codon suppression is required for pol gene expression. Removal of the gag stop codon had little or no effect on synthesis or cleavage of the polyprotein but interrupted particle assembly. This block could be overcome by complementation with wild-type gag protein. PMID- 2186175 TI - Human immunodeficiency virus-like, nonreplicating, gag-env particles assemble in a recombinant vaccinia virus expression system. AB - We report the assembly of human immunodeficiency virus (HIV)-like particles in African green monkey kidney cells coinfected with two recombinant vaccinia viruses, one carrying the HIV-1 gag and protease genes and the other the env gene. Biochemical analysis of particles sedimented from culture supernatants of doubly infected cells revealed that they were composed of gag proteins, primarily p24, as well as the env proteins gp120 and gp41. Thin-section immunoelectron microscopy showed that these particles were 100 to 120 nm in diameter, were characterized by the presence of cylindrical core structures, and displayed the mature gp120-gp41 complexes on their surfaces. Furthermore, thin-section immunoelectron microscopy analysis of infected cells showed that particle assembly and budding occurred at the plasma membrane. Nucleic acid hybridization suggested that the particles packaged only the gag mRNA but not the env mRNA. Therefore, the system we present is well suited for studies of HIV virion maturation. In addition, the HIV-like particles provide a novel and attractive approach for vaccine development. PMID- 2186176 TI - Sequence-specific binding of DNA by the Moloney murine leukemia virus integrase protein. AB - Genetic studies have indicated that integration of retroviral DNA into the host genome depends on the presence of the inverted repeats at the free termini of the long terminal repeats on the unintegrated DNA and on the product of the 3' end of the pol gene (the integrase [IN] protein). While the precise function of the Moloney murine leukemia virus IN protein is uncertain, others have shown that it is a DNA-binding protein and functions in the processing of the inverted repeats prior to integration. By using site-directed mutagenesis, we cloned and expressed the IN protein in Escherichia coli. Crude extracts of total cellular protein were fractionated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transferred to nitrocellulose filters, denatured in guanidine, renatured, and incubated with oligonucleotide probes. Single- and double-stranded oligonucleotides corresponding to the termini of unintegrated linear viral DNA were specifically bound by the IN protein in this assay. These data suggest that the role of the Moloney IN protein in the early steps of integration involves sequence-specific recognition of the DNA sequences found at the ends of the long terminal repeats. PMID- 2186177 TI - Constitutive expression of human immunodeficiency virus (HIV) nef protein in human astrocytes does not influence basal or induced HIV long terminal repeat activity. AB - Since human immunodeficiency virus (HIV) nef has been suggested to exert regulatory effects on HIV long terminal repeat (LTR) activity, we transiently transfected HIV LTR chloramphenicol acetyltransferase or luciferase expression vectors into a human astrocytoma clone (U-373nef) that constitutively expresses the HIV nef gene. In these cells, basal HIV LTR activity, as well as tumor necrosis factor-induced or tat-driven activity, was similar to that in control cells. Lack of any detectable effect of HIV nef on LTR activity was not the result of mutations in integrated nef DNA, as was shown by polymerase chain reaction. These data suggest that the role of nef in HIV genome transcription does not necessarily involve a direct influence on HIV LTR activity. PMID- 2186178 TI - Chemical synthesis of biologically active tat trans-activating protein of human immunodeficiency virus type 1. AB - Full-length (86-residue) polypeptide corresponding to the human immunodeficiency virus type 1 tat trans-activating protein was chemically synthesized on a semiautomated apparatus, using an Fmoc amino acid continuous-flow strategy. The bulk material was relatively homogeneous, as judged by sodium dodecyl sulfate polyacrylamide gel electrophoresis and isoelectric focusing, and it showed trans activating activity when scrape loaded into cells containing a human immunodeficiency virus long terminal repeat-chloramphenicol acetyl-transferase reporter plasmid. Reverse-phase high-pressure liquid chromatography yielded a rather broad elution profile, and assays across the column for biological activity indicated a sharper peak. Thus, high-pressure liquid chromatography provided for enrichment of biological activity. Fast atom bombardment-mass spectrometry of tryptic digests of synthetic tat identified several of the predicted tryptic peptides, consistent with accurate chemical synthesis. PMID- 2186179 TI - Mechanism of antibody-mediated viral clearance in immunotherapy of respiratory syncytial virus infection of cotton rats. AB - Antibody-mediated clearance of respiratory syncytial virus from cotton rat pulmonary tissues occurs in the absence of complement and in the absence of the Fc portion of the immunoglobulin G molecule, suggesting that complement independent, cell-independent neutralization is the major mechanism of clearance. PMID- 2186181 TI - Vascular surgery--the third generation. PMID- 2186180 TI - The carboxy terminus of human immunodeficiency virus type 1 gp160 limits its proteolytic processing and transport in transfected cell lines. AB - Mutagenesis of the transmembrane domain and cytoplasmic tail of human immunodeficiency virus type 1 envelope glycoprotein gp160 revealed that its intracellular transport and processing in transfected cell lines were modulated by a functional domain included in the carboxy-terminal sequence consisting of residues 751 to 856. PMID- 2186182 TI - Should patient age be a consideration in carotid endarterectomy? AB - Age as a factor in the selection of patients for carotid endarterectomy was studied with a retrospective evaluation of the perioperative and late results of procedures performed on 115 elderly patients. The results were taken from an experience of 685 operations performed on 607 patients. Perioperative results in 420 patients under 75 years of age (560 operations) were compared with results in 115 patients over 75 years of age (125 operations). Statistical comparison revealed a greater proportion of men in group I (66%, 55%, p = 0.0186) and a greater proportion of patients in group II with contralateral carotid stenosis (24%, 33%, p = 0.0382) and stroke as a preoperative indication for operation (14%, 22%, p = 0.0393). No statistical difference was found between group I and group II as regards other operative indications, contralateral carotid occlusion, bilaterality of operation, emergency operation, operation for recurrent carotid disease, frequency of shunt use, perioperative wound bleeding, and perioperative transient ischemic attack. Ipsilateral perioperative stroke occurred in 12 patients (2%), with all strokes occurring in the younger group of patients (2.4%) (NS). Perioperative death occurred in six (1%) patients, with five deaths (1%) occurring in the younger group (cardiac, 2; stroke, 2; protamine reaction, 1) and one (0.9%) death occurring in the elderly group of patients (ruptured abdominal aortic aneurysm) (NS). Life-table analysis of the late results of the 115 elderly patients revealed cumulative survival rates of 85.4% and 63.8% at 2 and 5 years, respectively. The principal causes of late death were cardiac (48%), cancer (15%), and stroke (9%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186183 TI - Myocardial ischemia caused by postoperative malfunction of a patent internal mammary coronary arterial graft. AB - The internal mammary artery is used with increasing frequency for myocardial revascularization. However, preoperative coronary angiography does not always provide adequate visualization of subclavian arteries. If a proximal subclavian artery stenosis exists or develops in a patient who has myocardial revascularization with the internal mammary artery, graft malfunction can occur resulting in myocardial ischemia. We have identified four cases of internal mammary artery graft malfunction at our own institution and identified an additional 12 cases from the literature. These 16 cases are analyzed for age, sex, time of onset of symptoms, clinical findings, method of revascularization, and long-term follow-up. Sixty-three percent of the patients were men, and the mean age was 52.9 +/- 9.0 years. Onset of symptoms occurred after a mean interval of 25.1 months from the time of myocardial revascularization. Three patients had asymptomatic reversal of flow in the internal mammary artery as diagnosed by coronary arteriography during routine follow-up examination before 1980. One death after internal mammary artery-coronary bypass grafting was related to immediate malfunction. In the remaining 12 patients with symptomatic malfunction, all but one were treated by placement of a carotid-subclavian bypass graft with no mortality. Relief of myocardial ischemia was complete in 93% of the patients with a mean follow-up of 29.3 months. Carotid-subclavian bypass grafting appears to be the treatment of choice for the usual management of internal mammary artery graft dysfunction. Careful preoperative evaluation and postoperative follow-up of the subclavian arteries, even by simple comparison of bilateral arm blood pressure should help reduce the incidence of this syndrome. PMID- 2186184 TI - Pitfalls in lower extremity venous duplex scanning. AB - Results of scans performed on 1074 patients over an 18-month period were evaluated to define the limitations of lower extremity venous duplex scanning. Eighty-four patients had confirmatory phlebography performed within 24 hours of their venous duplex scanning. In 71 patients scans were considered diagnostic (sensitivity 91%, specificity 95%). Eighteen studies (13 equivocal, 5 misinterpretations) were scrutinized to determine the limitations of venous duplex scanning compared to phlebography and are the focus of this analysis. Seven patients had phlebograms documenting only infrapopliteal thrombus, seven had normal phlebographic findings, and four had findings consistent with chronic thrombosis. In the seven patients with infrapopliteal thrombus, four had normal imaging outcomes but abnormal Doppler flow patterns, whereas three had both normal imaging results and flow patterns. All four patients with chronic thrombosis had identifiable thrombus and abnormal flow patterns by venous duplex scanning, but in each case thrombus age was indeterminate. Of the seven patients with normal phlebographic results, five had incompressible segments of the superficial femoral vein on imaging, one had abnormal Doppler flow without visualized thrombus and without apparent reason, one had venous duplex scanning visualized thrombus with a normal outcome on phlebography. These data suggest that the diagnostic yield of lower extremity venous duplex scanning may be improved by (1) meticulous infrapopliteal vein examination, (2) better estimation of the age of the thrombotic process, and (3) recognizing segmental incompressibility of the superficial femoral vein within the adductor canal as a normal finding especially in the absence of abnormal Doppler flow or imaged thrombus. PMID- 2186185 TI - Mesenteric flow velocity variations as a function of angle of insonation. AB - This study was designed to quantitate variations in duplex ultrasound arterial flow velocities (cm/sec) in the common carotid artery and the superior mesenteric artery that were produced by changes in the angle of pulsed Doppler insonation. Duplex scanning was used to measure peak systolic flow velocity and mean velocity at angles from 30 degrees to 80 degrees; individual measurements were made at 10 degree increments in both the common carotid artery and the superior mesenteric artery in normal subjects. Peak systolic velocity in the common carotid artery varied from 86 cm/sec at 30 degrees to 168 m/sec at 80 degrees. Over the same transducer angle variation mean velocity ranged from 28 to 53 cm/sec. Similar changes in the superior mesenteric artery flow velocities were observed by varying the angle of insonation, where peak systolic velocity varied from 108 cm/sec (30 degrees) to 280 cm/sec (80 degrees), and mean velocity ranged from 29 cm/sec (30 degrees) to 71 cm/sec (80 degrees). Measurements taken from 70 to 80 degrees produced the most dramatic deviation from those taken at 60 degrees. In the common carotid artery the 70- and 80-degree angles produced 14% and 59% increases, respectively, in peak systolic velocity and 16% and 63% increases, respectively, in mean velocity. In the superior mesenteric artery 70-degree and 80-degree angles produced 16% and 120% increases, respectively, in peak systolic velocity and 17% and 111% increases, respectively, in mean velocity. At 80 degrees the percent increases in measured flow velocities for the superior mesenteric artery were significantly greater than those for the common carotid artery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186186 TI - Total occlusion of the common carotid artery with a patent internal carotid artery; identification by duplex ultrasonography: report of a case. PMID- 2186187 TI - [Penetration of the anti-arrhythmia preparation ethmozin through the hemato encephalic barrier of the guinea pig brain perfused in situ]. AB - In experiment with an artificially perfused guinea-pig brain, labelled ethmosine possessing gamma-activity was used to study the penetration of the drug through the blood-brain barrier. The ethmosine transport constant was found to be in a range of 0.45-0.62 x 10(-3) ml x min-1 x g-1 for various segments of the anterior brain, suggesting that the agent penetrated into the central nervous system very slowly. The slight penetration of ethmosine through the blood-brain barrier may be one of the reasons for this phenothiazine derivative having no marked neurotropic activity. PMID- 2186188 TI - [Graded physical exercise and urinary excretion of albumin and beta 2 microglobulin in patients with hypertension]. PMID- 2186189 TI - [Arrhythmogenic effect of anti-arrhythmia drugs: incidence, possible mechanisms and therapeutic tactics]. PMID- 2186190 TI - [Formation of a smooth-muscle cuff around perineal colostomy after extirpation of the rectum]. PMID- 2186191 TI - [A method of gastropancreatoduodenal resection]. PMID- 2186192 TI - [A method of creation of esophagoduodenoanastomosis]. PMID- 2186193 TI - [Surgical treatment of myasthenia gravis (review of the literature)]. PMID- 2186194 TI - [Use of the greater omentum in operations on the thoracic wall, mediastinal organs and lungs (review of the literature)]. PMID- 2186195 TI - [Ultrasonic semeiotics and diagnosis of acute cholecystitis]. AB - From analysis of the results of ultrasonic examination in 1,428 patients with acute cholecystitis the authors determined the semeiotics of various forms and complications of the disease. The most common ultrasonic sign of acute cholecystitis is a triad of symptoms: enlarged gallbladder, thickened walls, and fixed hyperchostructures with an acoustic shadow in the projection of the neck of the gallbladder. Ultrasonic examination allows the presence of destructive cholecystitis to be detected with high precision on basis of the sign of a double gallbladder contour. Complications like pericystic infiltration, pericystic abscess with or without perforation, empyema of the gallbladder, acute pancreatitis, and choledocholithiasis can also be recognized in patients with acute cholecystitis by ultrasonic examination. Comparison of the data of ultrasonic examination with those obtained in laparoscopy or operation showed that the diagnosis coincided in 98.9% of cases. PMID- 2186196 TI - [Ultrasonic evaluation of the course of the wound process after cholecystectomy]. AB - The authors conducted 101 ultrasonic studies in patients in the early period after cholecystectomy. They studied the ultrasonic semeiotics of the course of the wound process in the zone of the operation. Three types of an uncomplicated course of the wound process in the zone of the operation were determined. An image of the sutured site of the gallbladder with no additional structures in the subhepatic space was encountered in most cases (variant I). In other cases (variants II and III) areas indicative of the accumulation of fluid in the subhepatic space and in the projection of the gallbladder site were visualized. This calls for a case follow-up and, in some cases, for preventive treatment. PMID- 2186197 TI - [Reoperations in ulcer recurrence after surgical treatment of peptic ulcer]. AB - Operations were carried out on 60 patients with recurrent ulcers after closure of perforated gastroduodenal ulcers (49), resection of the stomach (9), and gastroenterostomy (2). Various complications of the ulcer were encountered in 46 of them. A relationship was found between the recurrence and the inadequacy of antiulcerative therapy after closure of the perforated ulcers. The reoperations consisted in resection (48) and reresection (6) of the stomach and other operations (6). Two (3.3%) patients died after the operation. Resection and reresection of the stomach are the operations of choice in recurrent ulcers. PMID- 2186198 TI - [Evaluating diagnostic measures]. PMID- 2186199 TI - [Ultrasonic examination of the liver in patients with pulmonary tuberculosis]. PMID- 2186200 TI - [Georgii Pavlovich Rudnev (1899-1970)]. PMID- 2186201 TI - [K.V. Volkov, a prominent Russian surgeon (on the 50th anniversary of his death)]. PMID- 2186202 TI - [History of F.I. Tiutchev's illness]. PMID- 2186203 TI - [Status of the hepatobiliary system in patients with rheumatoid arthritis]. PMID- 2186204 TI - [Laboratory diagnosis of visceral disorders in alcoholism]. PMID- 2186205 TI - [Use of mindronate in cardiac insufficiency in patients with ischemic heart disease]. AB - A clinical trial of Soviet drug mildronate has proved its antiarrhythmic action, the ability to prevent ventricular extrasystoles, to reduce asthenia, to enhance physical performance and adaptive reactions. The heart rate decrease appeared insignificant. Intravenous administration of the drug improves myocardial contractility. Mildronate is well tolerated. No side effects were registered. PMID- 2186206 TI - [Richard Bright and the nephrological theory of E.M. Tareev]. PMID- 2186207 TI - [Various problems of differential diagnosis of arterial hypertension]. PMID- 2186208 TI - [Effectiveness of adrenergic beta 1 receptor agonists in the correction of hemodynamics in patients with chronic cor pulmonale]. PMID- 2186209 TI - [Experience with using plasmapheresis in the treatment of hormone-resistant bronchial asthma]. PMID- 2186210 TI - [Genetic aspects of diabetes mellitus]. PMID- 2186211 TI - [Acute abscesses and gangrene of the lungs in patients with diabetes mellitus]. AB - Decompensation of diabetes mellitus is known to promote acute pulmonary suppuration taking a complicated course in 46% of the cases. New effective methods of the prevention and treatment of purulent diseases in diabetics are awaited. PMID- 2186212 TI - [Myocardial infarction in young persons]. PMID- 2186213 TI - [The Clinical Research Institute of Montreal and the Memorial University of Newfoundland]. PMID- 2186214 TI - [Heroine of 3 wars]. PMID- 2186215 TI - [Rare forms of pulmonary lymphogranulomatosis]. PMID- 2186216 TI - [Vitamin C and diabetes mellitus]. PMID- 2186217 TI - [Clinical significance of the urinary syndrome. Proteinuria]. PMID- 2186219 TI - [The main results and prospects of the development of radiation medicine]. PMID- 2186218 TI - [Circadian changes in arterial blood pressure and hemodynamics and the morphofunctional state of the myocardium in patients with hypertension during long-term treatment with estulic]. AB - The schedule of estulic administration for stage I-II essential hypertension in more effective at lower doses and better tolerance when adjusted to circadian variations in arterial pressure. Six-month continuous estulic treatment results in regression of left ventricular myocardial hypertrophy. PMID- 2186220 TI - [Use of phthivazide in the treatment of patients with acute pneumonia and chronic bronchitis]. AB - The treatment scheme of 540 patients with acute pneumonia and chronic bronchitis involved a 0.5 g ftivazid three times a day for 15-20 days. Compared with control groups of patients on the standard therapy, the drug presents a more advantageous treatment. Adequate efficacy and tolerance of the drug ftivazid make it appropriate for use in acute pneumonia and chronic bronchitis. PMID- 2186221 TI - [Clinical use of echotomography with target aspiration biopsy and urgent cytological examination]. AB - Upon analysis of the results obtained at cytological examinations of the biopsies performed by target aspiration puncture under the control of ultrasound tomography in 240 patients with various diseases, it was established that combination of aspiration puncture, ultrasound tomography and rapid cytological evaluation improve diagnosis of various diseases, reduce the duration of the examination, increase the quality of treatment. PMID- 2186222 TI - Plants used in traditional medicine in eastern Tanzania. III. Angiosperms (Euphorbiaceae to Menispermaceae). AB - Seventy-seven Angiosperms (Euphorbiaceae to Menispermaceae) are listed, which are used by traditional healers in five regions of Eastern Tanzania; namely, Coast, Dar es Salaam, Kilimanjaro, Morogoro and Tanga. For each species listed, the botanical name, vernacular name, collection number, locality, habit, distribution and medicinal uses are given. Additionally, information from the literature on medicinal uses, chemical constituents and pharmacological effects is also provided. PMID- 2186223 TI - Effects of shosaikoto, an oriental herbal medicinal mixture, on restraint stressed mice. AB - Restraint-induced stress produced an inhibition of humoral immune responses accompanied by a decrease of rectal temperature and motor activity. Diazepam and levamisole restored the decrease of humoral immune responses. Furthermore, diazepam restored the decrease of rectal temperature. Shosaikoto, an oriental herbal medicinal mixture, restored the stress-induced inhibition of humoral immune responses and rectal temperature. PMID- 2186224 TI - Labelling neurons with fluorescent dyes administered via intravenous, subcutaneous or intraperitoneal route. AB - Fast blue, true blue and fluorogold injected into neonatal and subadult rats via subcutaneous or intraperitoneal route labelled certain forebrain nuclei and the central and peripheral neurons whose axons form the spinal and most cranial nerves. The A1 and A5 noradrenergic neurons, nucleus of the tractus solitarius and some neurons in the nucleus raphe medianus, nucleus reticularis gigantocellularis were also labelled. In addition, occasional fluorescent neurons were seen in the vestibular nucleus, locus coeruleus, fastigial nucleus and Purkinje cell layer of the cerebellum. Some nuclei labelled in neonatal rats hardly showed any labelled neurons in subadult rats. After injection the subarachnoid space, blood vessels in the spinal cord, brain and peripheral ganglia, the circumventricular organs and the choroid plexuses were labelled much faster than the neurons. A similar pattern of labelling was seen in subadult rats receiving intravenous injection of fluorogold. Evans blue and rhodamine injected intravenously failed to label any neurons in the brain or spinal cord. PMID- 2186225 TI - [Antibiotic sensitivity of strains of group A beta-hemolytic streptococci isolated recently]. AB - The present study investigated the sensitivity of 35 group A beta-hemolytic streptococci strains, isolated from clinical samples in 1988 and 1989, to 12 antibiotics. The minimal inhibitory concentrations of each antibiotic were measured by the agar dilution method. All strains were sensitive to penicillin G, ampicillin, oxacillin, cefazolin, cefotaxime, erythromycin, clindamycin, vancomycin and ciprofloxacin. It was concluded that, in our area, Streptococcus pyogenes still has an excellent sensitivity to penicillin G and to other antibiotics which may be a therapeutic alternative in allergic patients or an empiric treatment in infections likely to be produced, among other organisms, by S. pyogenes. PMID- 2186226 TI - [The molecular bases of the cachexia associated with cancer]. PMID- 2186227 TI - [Evaluation of the variability of rapid diagnosis of infection by Chlamydia trachomatis using direct immunofluorescence]. AB - The interobserver and intraobserver agreement between two microscopists was independently assessed in a blind fashion to evaluate the reproducibility of the results of the quick diagnosis of Chlamydia trachomatis infection with direct immunofluorescence. The study was carried out in two phases, and 604 samples of cervical and urethral exudate from patients seen at a center for the prevention and therapy of sexually transmitted diseases were evaluated. The two observers had a kappa index of agreement between them of 0.41, with 95% confidence intervals (95% Cl) of 0.31-0.51, while their agreement within themselves was 0.78 (95% Cl: 0.65-0.91) for the first observer and 0.61 (95% Cl: 0.47-0.75) for the second one. After discussion of the data and analysis of the reasons of disagreement, the evaluation was repeated. In this second phase, both interobserver and intraobserver agreement were substantially improved. The kappa index was 0.71 (95% Cl: 0.61-0.80) for the former, whereas regarding the latter the first observer had a kappa index of 1 (95% Cl: 0.86-1.13) and the second observer an index of 0.82 (95% Cl: 0.61-0.80). It was concluded that the test may have problems in its practical performance if the microscopists are not previously trained with systematic programs for the evaluation of results. PMID- 2186228 TI - [Rheumatoid arthritis and food]. PMID- 2186229 TI - [Pleural tuberculosis]. PMID- 2186230 TI - [Cardiopathy and pregnancy]. PMID- 2186231 TI - [Changes in the renin plasma and aldosterone activity induced by a progressive administration schedule of zinc sulfate in normotensive individuals]. PMID- 2186232 TI - Airways obstructive diseases: pathogenetic mechanisms and natural histories of the disorders. AB - There has been a long-standing controversy concerning the risk factors and pathogenetic mechanisms involved in the development of chronic airflow obstruction (CAO). This asthmatic constitution consisted of a predisposition to allergy, airways hyperresponsiveness, and possibly eosinophilia. Other investigators, however, regarded CAO as simply the late stage of chronic bronchitis. The term chronic obstructive lung disease (COLD) was developed to resolve what was largely a semantic difference. In subsequent years, the term chronic obstructive pulmonary disease (COPD) has come to be used more often than COLD to describe these patients. This article discusses the differences between these terms and defines the causes and risk factors associated with each. PMID- 2186233 TI - Relationship between airways responsiveness and the development of chronic obstructive pulmonary disease. AB - The idea that increases in airways responsiveness--either as a result of exposure to cigarette smoke and/or pre-existing increases in bronchial responsiveness, possibly genetically mediated--might be causal in the pathogenesis of the development of COPD in cigarette smokers presents an attractive hypothesis. The fact that a relatively small proportion of cigarette smokers develop COPD begs for specific susceptibilities as an explanation of selective pathogenesis. In our view, the evidence for modest increases in airways responsiveness in cigarette smokers who do not have asthma or allergies is convincing. Such increases in bronchial responsiveness are modest when compared to patients with asthma and may have a different mechanism. However, the demonstration by Verma et al that two types of patients with cigarette smoke-induced COPD, "bronchitis" patients and "emphysematous" patients, have virtually identical alterations in bronchial responsiveness, and that these alterations appear to be a function of airways caliber, has led us to believe that the changes in airways tone in patients with COPD may be reflective more of changes in airways geometry imposed by the development of disease rather than a measurement of a risk factor in the development of COPD. Of the epidemiologic studies that have emerged throughout the 1980s, problems of possible inclusion of asthmatic subjects in the study groups and of baseline airflow rates as a function of bronchial responsiveness have limited the ability of data to implicate increases in airways responsiveness as a risk factor in the development of COPD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186234 TI - Cardiovascular-pulmonary interaction in chronic obstructive pulmonary disease with special reference to the pathogenesis and management of cor pulmonale. AB - Chronic obstructive pulmonary disease (COPD), which here refers to a group of diseases that have in common the physiologic defect of airway obstruction, is often associated with severe hemodynamic consequences. This article provides an overview of cardiovascular function in COPD with emphasis on recent advances in detecting, quantifying, and treating pulmonary hypertension and its major cardiac complication, cor pulmonale. PMID- 2186235 TI - Exercise and chronic obstructive pulmonary disease. AB - Patients with chronic obstructive pulmonary disease have abnormal respiratory mechanics, respiratory muscle function, gas exchange, and cardiovascular function during exercise. Their impaired exercise tolerance is at least partly due to altered respiratory mechanics, but factors that increase ventilation during exercise indirectly contribute to exercise limitation. Clinical exercise testing is a very important tool in the assessment of exercise capacity, assessment of factors that contribute to exercise limitation, and differential diagnosis of cardiopulmonary disease. PMID- 2186236 TI - Assessment of respiratory muscle dysfunction in chronic obstructive lung disease. AB - In COLD, the inspiratory muscles are severely disadvantaged by virtue of the hyperinflation that accompanies this disorder. Such mechanical disadvantage will lead clinically, in the stable patient, to the active recruitment of the accessory muscles of inspiration and to a pattern of rapid, shallow breathing that may be due to either peripheral (muscle) or central (neurogenic) influences thought to be linked to a critical tension-time index of the inspiratory muscles. This pattern appears to be all the more pronounced in the patient with acute respiratory failure and is frequently accompanied by disordered rib cage abdominal movements. While these movements may reflect the muscles' attempts to stave off fatigue, they may also imply that if the imposed mechanical stress is unrelieved, muscle failure will ensue. In the laboratory, mechanical disadvantage is marked by diminished inspiratory mouth pressures. Because of wide scatter, a low mouth pressure beyond that which can be explained by hyperinflation alone should be confirmed by an assessment of Pesosniff or by the measurement of transdiaphragmatic pressure. Muscle endurance, also compromised in this condition, can be assessed indirectly by the measurement of MVV or MSVC, or more directly by an invasive assessment of the tension-time index and endurance time of the diaphragm or noninvasively by the Endurance Index of McKenzie and Gandevia. And finally, once muscle failure is pending or has been established, a program of muscle rest, either complete or partial, pharmacotherapy, and goal specific training should be instituted. PMID- 2186237 TI - Rationale and use of corticosteroids in chronic obstructive pulmonary disease. AB - Several studies of corticosteroid efficacy in patients with COPD performed in the last decade have had stronger study designs and larger patient populations than most of the previously reported investigations. These studies have provided evidence of the objective benefit of corticosteroid therapy on pulmonary function in clinically stable COPD patients. These positive results are due to a relatively marked beneficial effect of corticosteroids in a minority of the subjects studied rather than a modest effect in the majority of subjects. A controlled randomized trial of intravenous corticosteroid administration in patients with COPD and acute respiratory failure admitted to the hospital showed improvement in pulmonary function from 12 hours following initial administration through the remainder of the 3 days of the study in the treatment group as compared to the control group. A greater percentage of patients showed a beneficial response to corticosteroids in this study of patients with acute exacerbations as compared to most of the studies of clinically stable COPD patients with beneficial effects. This suggests the possibility that some patients may show a beneficial response to corticosteroids during an acute exacerbation although they have not shown a response when clinically stable. The response to inhaled corticosteroids in patients with COPD has not been studied as extensively as the response to oral corticosteroids. However, some studies have shown a beneficial response to inhaled corticosteroids, primarily but not exclusively, in individuals who have also shown a positive response to oral agents. Generally, the response in terms of improved pulmonary function has been less striking with the inhaled agent as compared to the oral drug, although higher relative doses of the oral drugs usually were studied. Several limitations of the currently available studies are evident. Most of the studies deal with the effects in clinically stable outpatients with COPD and no studies have dealt with maintenance therapy in patients who have responded to a 1 to 2 week course of 30 mg of prednisone or greater. Data on the efficacy of inhaled corticosteroids in COPD patients are limited. No studies have investigated the role of corticosteroids in acute exacerbations in outpatients with COPD. Recommendations are given regarding use of corticosteroids in patients with COPD. A trial of corticosteroids is recommended at some point during a patient's course, while clinically stable. If a beneficial response is obtained in terms of improvement in airflow obstruction, then clinical judgment must be used regarding whether maintenance therapy is continued and, if so, at what dose and by what route.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2186238 TI - The sleep-related worsening of lower airways obstruction: understanding and intervention. AB - The area of circadian rhythms and sleep altering lung function is relatively new to medicine. It is important to understand these changes to prevent complications from disease processes and to deliver the appropriate therapy over the entire day. This article focuses on the alterations during sleep in patients with lower airways obstruction. Asthma and chronic obstructive pulmonary disease are used as examples. Clinical and physiologic changes are discussed as well as treatment modalities. PMID- 2186239 TI - Mucosal permeability and smooth muscle function in asthma. AB - The changes in airway structure that occur in asthma are characteristic of a chronic inflammatory process that involves tissue covered by a mucosal surface. This article reviews the inflammatory process and presentation of evidence that structural changes seen in asthmatic airways are a result of this response. The contribution of the airway muscle and epithelium to the abnormal function of asthmatic airways is also reviewed. PMID- 2186240 TI - Differences in airway responsiveness in asthma and chronic airflow obstruction. AB - In patients with chronic obstructive lung disease, it is difficult to distinguish clinically between asthma, chronic bronchitis, and emphysema. This is due in part to the fact that the original definitions were not mutually exclusive. Diagnosis has not been helped by the measurement of airway responsiveness to methacholine or histamine, since responsiveness seems to be increased as often in those with chronic airflow obstruction as in asthmatic patients. PMID- 2186241 TI - Assessment of bronchial responsiveness as a guide to prognosis and therapy in asthma. AB - The severity of airway inflammation in patients with asthma is best assessed by combining several tests of bronchial responsiveness. The prognostic significance of bronchial responsiveness is unknown, but indirect evidence suggests that those with moderate and severe asthma rarely remit spontaneously and permanently. Assessment of severity is crucial to the rational management of all patients with asthma. Severity can be used as a guide to both short- and long-term management. PMID- 2186242 TI - The clinical value of pharmacologic bronchoprovocation challenge. AB - Pharmacologic bronchoprovocation challenge (PBC) can be of considerable clinical value in patients in the pediatric age group and adults because bronchial hyperresponsiveness is present in virtually all symptomatic asthmatics and it can be accurately, reliably, and safely demonstrated by PBC. The principal, proven indication for performing PBC is to rule out or help rule in the diagnostic possibility of asthma as the cause of any unexplained chest complaints in patients with normal or near normal spirometric values. PMID- 2186243 TI - Management of the critically ill asthmatic patient. AB - Status asthmaticus is a life-threatening condition characterized by rapid or inexorable progression of airflow obstruction that may lead to respiratory failure. It must be distinguished from other causes of dyspnea with signs of airflow limitation, and therapy must then be directed at relief of bronchospasm and airway inflammation, with use of multiple pharmacologic agents. Patients require moment-to-moment assessment until airway disease reverses. During this early portion of their course, intubation and mechanical ventilation may be required. Successful management on the ventilator requires an understanding of underlying abnormalities of lung mechanics and the interaction of the lungs and circulation. PMID- 2186244 TI - Outpatient management of bronchial asthma. AB - The current approach to asthma treatment centers around the recognition that asthma is primarily an inflammatory condition; airway hyperresponsiveness and bronchospasm are secondary phenomena. Anti-inflammatory treatments that produce sustained improvement in airway hyperresponsiveness (environmental control, cromolyn, inhaled and ingested corticosteroids) are the mainstay of treatment to keep symptoms and bronchodilator use to a minimum. Adequate control of chronic asthma with clearly defined treatment goals, accompanied by early recognition and patient-initiated treatment of worsened asthma, generally with inhaled/ingested corticosteroid, can successfully reduce the high morbidity and the low, but significant, mortality from this common condition. PMID- 2186245 TI - A clinician's approach to determine the diagnosis, prognosis, and therapy of occupational asthma. AB - A large number of agents in the workplace cause occupational asthma. With the rapid introduction of new compounds into industries, it is likely that the prevalence of occupational asthma will continue to increase. This article defines occupational asthma as well as reviews the current tests used in diagnosing occupational asthma and therapies for treatment of patients. PMID- 2186246 TI - Occupational obstructive disorders: nonspecific airways obstruction and occupational asthma. AB - Airways obstruction as a result of occupational exposure may be divided into two categories on the basis of whether or not occupational asthma is present. The first category, nonspecific airways obstruction, takes place in the absence of occupational asthma, and demonstrates only modest changes in airways responsiveness. The second category, occupational asthma, usually has a causal relationship to exposure, and demonstrates marked changes in airways responsiveness. These distinctions are of use in diagnosis, treatment, and disability assessment. PMID- 2186248 TI - [Rapid and dynamic development of HIV tests]. PMID- 2186247 TI - Antibacterial therapy in cystic fibrosis. AB - Bacterial lung infections determine the prognosis for most cystic fibrosis patients. The antibacterial therapy is difficult because of the host-bacterium interaction and altered pharmacokinetics. The new insights in the working mechanisms of antibiotics that may lead to better treatment results have been discussed, and guidelines for treatment of lung infections in cystic fibrosis patients were given. PMID- 2186249 TI - [Development of the method of ultrasound topometry of the thyroid gland and computer programs in the planning of radioactive iodine therapy]. AB - The paper is concerned with the problem of stereological volumenometry applied to the problems of ultrasound topometry of the thyroid. The organ surfaces are tightened on the basis of information obtained from echotomographic films using a method of cubic spline-interpolation, parametric function setting and methods of computer graphics. Images of sections can be obtained with an arbitrary step and an angle of inclination to the organ longitudinal axis. The main sources of errors of the method were estimated, and their numeric values were given. PMID- 2186250 TI - [Significance of echography in the diagnosis of diseases of the thyroid and parathyroid glands]. PMID- 2186251 TI - Automated translation between medical terminologies using semantic definitions. AB - Automatic translation of medical terms from one controlled vocabulary into another is essential to the integration of diverse medical informatics systems. We have developed a strategy in which medical terms are represented in a standard format that provides semantic description of the terms. We demonstrate the representational power of our method by showing that a subset of medical terms (procedures) from diverse vocabularies can be described in this manner. We assess the potential usefulness of our approach for facilitating automatic translation by finding the closest match for MeSH cardiovascular procedures with ICD-9 procedures. PMID- 2186252 TI - Learning theory and knowledge structures in computer-aided instruction. AB - The development of computer-aided instructional (CAI) systems suffers from a lack of a cohesive theory of learning--how do students acquire and store knowledge? From studies of computer systems that learn and tutor, we can infer generic activities that appear to be integral parts of the learning process, such as aggregation, clustering, characterization, and storage for later retrieval. Learning is faster and more efficient if the goal of a task is made explicit. Hints should be given with the correct timing in relation to an objective so that students can advance in their own problem-solving strategies with the prerequisites in mind. The general form of a rule should usually be taught first, followed by exceptions and special instances. We review theories of learning associated with CAI that illustrate the classification of different types of knowledge. Rule-based (if-then) knowledge forms are represented in these theories, as are declarative and causal knowledge structures. Extracting the common themes from different classifications of knowledge may help us create better CAI. PMID- 2186253 TI - [Laughter and smiling. The gesture between social philosophy and psychobiology]. AB - The human individual experiences his gestuality unaware, making it even more revelatory of his current state of mind. Certain actions represent innate behaviour, while others are discovered or assimilated during learning. The actions that signify the sending of any kind of message to another person, become "gestures". Laughter is an example of expressive behaviour and, as such, plays an important part in social interaction, insofar as it supplies signals that influence the response of other individuals. After a review of the philosophical and sociological interpretations inherent in laughing and smiling, the correlations between weeping, smiling and laughing are examined specifically from as ethological standpoint. The neurophysiological aspects whereby the crying, smiling and laughing mechanisms depend on a multifactorial control system, that implies the activation of limbic and frontal circuits, a motor cortex response and an activation of the autonomic response of the vegetative nervous system, correlated to the cortico-hypothalamic ways, are then examined. The pathological observations carried out in Man are identified with the study of psychomotor epilepsy in the context of "gelastic crises", cataleptic-gelolegic crises "and the pseudo-bulbar syndrome" with crying and spastic laughing. Finally, the possible therapeutic implications correlated with the laughing mechanism are discussed. In fact, the facial contractions, associated with the emotional experience connected with them, would appear to function as a standard brain signal. Interesting are the findings of changes in neuromediator and endorphin modifications implied in the neurophysiological smiling and laughing mechanism. A further basic element is the involvement of the autonomous system which can be correlated with the concept of the trophotropic response according to Hesse, with an increase in parasympathetic tone and reduction in sympathetic tone. PMID- 2186254 TI - [Pseudodementia. A critical review of the literature]. AB - A review is made of the concept of "pseudodementia" through the main studies of the literature on clinical series. These can be divided in homogeneous and heterogeneous diagnostic series. Some of the main methodological flows of the research on the subject are pointed out and the difficult problem of differential diagnosis between depressive pseudodementia and recent onset organic dementia is discussed. PMID- 2186255 TI - Obesity and insulin resistance in humans: a dose-response study. AB - Insulin-mediated glucose metabolism (euglycemic insulin clamp at plasma insulin concentration of 100 microU/mL) and glucose-stimulated insulin secretion (hyperglycemic clamp) were examined in 42 obese subjects (ideal body weight [IBW], 158 +/- 4%) with normal glucose tolerance and in 36 normal weight (IBW, 102% +/- 1%) age-matched controls. In 10 obese and eight control subjects, insulin was infused at six rates to increase plasma insulin concentration by approximately 10, 20, 40, 80, 2,000, and 20,000 microU/mL. Throughout the physiologic range of plasma insulin concentrations, both the increase in total body glucose uptake and the suppression of hepatic glucose production (HGP) were significantly impaired in the obese group (P less than .001 to .01). At the two highest plasma insulin concentrations, inhibition of HGP and the stimulation of glucose disposal were similar in both the obese and control groups. Insulin secretion during the hyperglycemic (+/- 125 mg/dL) clamp was twofold greater in obese subjects than in controls (P less than .01) and was inversely related to the rate of glucose uptake during the insulin clamp (r = -.438, P less than .05), but was still unable to normalize glucose disposal (P less than .05). In conclusion, our results indicate that insulin resistance is a common accompaniment of obesity and can be overcome at supraphysiological insulin concentrations. Both in the basal state and following a hyperglycemic stimulus obese people display hyperinsulinemia, which correlates with the degree of insulin resistance. However, endogenous hyperinsulinemia fails to fully compensate for the insulin resistance. PMID- 2186256 TI - The effect of starvation on insulin-induced glucose disposal and thermogenesis in humans. AB - The effect of 48-hour starvation on glucose metabolism was studied in six non diabetic, normal weight men using a hyperinsulinemic (100 mU/min/m2) glucose clamp (3.5 mmol/L). The rate of glucose oxidation was calculated from measurements of respiratory gas exchange, after allowing for the oxidation of ketones and of protein. During the glucose clamp, the whole body glucose disposal rate decreased from 39.8 (SEM 4.6) mumol/kg/min in the fed state to 24.1 (2.1) mumol/kg/min in the starved state (P less than .01), consistent with insulin "resistance." The glucose oxidation rate decreased from 21.8 (1.3) to 3.9 (1.4) mumol/kg/min with starvation (P less than .001), but the nonoxidative glucose disposal rate was unchanged (18.0 [3.9] mumol/kg/min normally fed, and 20.2 [1.2] mumol/kg/min starved). With starvation, the rate of glucose uptake in the forearm during the glucose clamp was reduced from 59.4 to 15.4 mumol/min/L forearm (SE 5.6, P less than .01, ANOVA). There was a significant net increase in thermogenesis during the glucose clamp in the normally fed state (0.27 [0.08] kJ/min, P less than .01, ANOVA), but not following starvation (0.11 [0.09] kJ/min, NS, ANOVA). Therefore, starvation caused decreases in oxidative glucose disposal and in forearm glucose uptake; despite the whole body nonoxidative disposal rate of glucose being unchanged, the associated net thermogenic response was diminished. PMID- 2186257 TI - Copper deficiency in pregnancy: effect on maternal and fetal polyol metabolites. AB - The present study was undertaken to determine whether the mortality of the fetus and the neonate of copper-deficient rats consuming fructose during pregnancy is associated with an aberration in carbohydrate metabolism. A total of 84 Sprague Dawley rats were fed a copper-deficient or a copper-adequate diet containing fructose or starch for 19 or 21 days after conception. The consumption of a fructose-based diet during pregnancy resulted in higher concentrations of maternal blood fructose, sorbitol, triglyceride, and uric acid when compared with a starch diet. The placenta contained more than 10-fold the concentration of glucose and more than double the concentrations of fructose, triglycerides, and sorbitol when fructose was the dietary carbohydrate compared with starch. The livers of fetuses belonging to the fructose dietary group exhibited high concentrations of glucose and sorbitol. In addition, fetal blood contained higher concentrations of glucose, fructose, sorbitol, and triglycerides than the corresponding values from the starch dietary group. The consumption of a copper deficient diet containing fructose during pregnancy resulted in massive subcutaneous hemorrhages of the fetus. In contrast, this pathology was rare in other dietary groups. The combination of copper deficiency with fructose feeding resulted in more than double the concentration of sorbitol in fetal liver, and higher concentrations of insulin and dopamine of fetal blood compared with the consumption of a copper-deficient diet containing starch.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186258 TI - Deloisteen Brown, MD. And the neighborhood health clinic--a model for low-cost care. PMID- 2186259 TI - [Bioequivalence of non-retard verapamil. Realization of a draft monograph exemplified by Veramex 80]. AB - The commercial preparation Veramex 80, containing 80 mg non-retarded Verapamil, was compared to the appropriate product being first on the market and containing the same amount of active substance according to the AMG 1976. This study was a randomized single-dose trial with a double cross-over-design and a one-week wash out phase between the individual test periods. Equivalence of the most relevant pharmacokinetic parameters was checked in 18 volunteers according to the latest recommendations and regulations of the Zentrallaboratorium Deutscher Apotheker (ZL) and the APV-guidelines. The mean AUC (0-24) after application of Veramex 80, calculated with 217.2 micrograms X h/l +/- 65.6, was approximately 10% less than the mean AUC (0-24) after application of the reference substance, which reached 240.4 micrograms X h/l +/- 87.0. The difference was statistically not significant and the 90%-confidence interval could be estimated with 0.82 to 1.01 which is in accordance with the postulated limits (0.8 to 1.2). After application of the reference drug the mean maximal concentration (cmax) of Verapamil was 58.1 micrograms/l and thus approximately 10% higher than the appropriate value detected after application of Veramex 80, which was 51.8 micrograms/l. Again, this difference was statistically not significant and the 90%-confidence interval, calculated with 0.76 to 1.05, was located within the postulated limits (0.7 to 1.3). Mean value, median and the range for tmax after application of Veramex 80 resp. reference substance were comparable and differences were less than 30 minutes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186260 TI - [Treatment of myocardial ischemia with molsidomine]. PMID- 2186261 TI - [Treatment of hypogonadism and infertility in the male. II]. PMID- 2186262 TI - [Prevention of pediatric respiratory distress syndrome with special reference to glucocorticoids]. PMID- 2186264 TI - Radiologists as swimmers and surfers. PMID- 2186263 TI - [Usefulness of an amoxicillin/clavulanic-acid combination in respiratory tract infection: bacterial resistance and antibiotic therapy]. AB - The continual use of antibiotics and the defence works of microorganisms have induced less activity of many antibiotics once particularly effective for their excellent therapeutic index. The association of clavulanic acid with amoxicillin, the latter a long time used for its excellent therapeutic index particularly in respiratory tract infections, has restored and some ways potentiated the once activity of the latter. PMID- 2186265 TI - Treatment of acute herpetic neuralgia. A case report and review of the literature. AB - Herpes zoster (shingles) is a viral infection that results from a reactivation of a dormant varicella zoster virus. It has been estimated that more than 300,000 new cases are seen in the United States each year. Several factors influence the incidence of infection, with increasing age being the most consistent. Postherpetic neuralgia is the No. 1 cause of intractable, debilitating pain in the elderly and is the leading cause of suicide in chronic pain patients over the age of 70. PMID- 2186266 TI - The rise and fall of medical specialists? PMID- 2186267 TI - Positive and negative symptoms: historical and conceptual aspects. AB - The re-emergence of interest in negative symptoms during the past decade has generated a creative period for the study of psychopathology in schizophrenia. Increasingly, a relative balance has been restored to descriptive psychopathology, giving more equal emphasis on florid colorful symptoms such as delusions and hallucinations as well as the more debilitating negative symptoms. An emphasis on considering the neural mechanisms that may underlie both positive and negative symptoms has led to a more focused approach to asking questions about psychopathology, particularly emphasizing the importance of longitudinal perspectives and the possible interaction between treatment effects and psychopathology. These developments cannot help but improve the quality of both basic and clinical research in schizophrenia during the next decade. PMID- 2186268 TI - Evidence for the validity of negative symptoms. PMID- 2186269 TI - Relationship between brain imaging findings in schizophrenia and psychopathology. A review of the literature relating to positive and negative symptoms. PMID- 2186270 TI - Mutagenic activity of pyrolysates of cyanocobalamin and some other water-soluble vitamins in the model system with the Salmonella/mammalian microsomes. AB - Pyrolysates of cyanocobalamin, thiamine hydrochloride, riboflavin, pyridoxine hydrochloride, and ascorbic acid were tested for mutagenicity in the histidine requiring mutants Salmonella typhimurium TA98 and TA100. Each vitamin was sealed in a glass tube and heated at 100-600 degrees C in a muffle furnace. Methanol chloroform extracts of the pyrolysate of each vitamin tested did not show any mutagenicity in either TA98 or TA100 without rat liver 9000 x g supernatant fraction (S9) added. In the presence of S9, the B-group vitamins (cyanocobalamin, thiamine hydrochloride, riboflavin, and pyridoxine hydrochloride) were all mutagenic in TA98 and TA100, with the highest activity among the vitamins tested found in the pyrolysate of cyanocobalamin. The pyrolysate of 0.25 mumole cyanocobalamin produced 3200 revertants, while the pyrolysates of 0.25 mumole thiamine hydrochloride and riboflavin produced only 910 revertants, and the pyrolysate of pyridoxine hydrochloride did not show any mutagenicity at that amount. The mutagenicity was generally more active to TA98 than to TA100, indicating that frameshift-type mutagens were contained in the pyrolysates. The pyrolysate of ascorbic acid did not show any mutagenic activity in either TA98 or TA100 under the present experimental conditions. PMID- 2186271 TI - An association between mutagenicity and carcinogenic potency. AB - A comparison between mutagenic and non-mutagenic rodent carcinogens studied by the U.S. National Toxicology Program revealed that as a group, rat carcinogens mutagenic in Salmonella typhimurium are more potent than their non-mutagenic counterparts. PMID- 2186272 TI - Salmonella/mammalian microsome assay with tetranitromethane and 3-nitro-L tyrosine. AB - The nitrosating agent tetranitromethane (TNM) and the nitrosation product 3-nitro L-tyrosine (NT) were tested for mutagenic activity in the Salmonella/mammalian microsome assay. TNM showed strong genotoxic activity: it was mutagenic in all tester strains used (TA97, TA98, TA100, and TA102). The maximum mutagenic activity was reached between 16 and 32 micrograms/plate using the standard plate test; higher amounts led to distinct bactericidal effects. The mutagenicity was independent of an in vitro activation system. In the preincubation assay an increased bactericidal effect was observed. In contrast to TNM, NT, the nitrosation product, was non-mutagenic and non-toxic in the standard plate test and with the preincubation method up to 5000 micrograms/plate with and without S9 mix and with all tester strains used. Although TNM is a strong direct-acting mutagen, its nitrosating effect on proteins does lead to nongenotoxic nitro products of tyrosine in proteins. PMID- 2186273 TI - Recombinant human erythropoietin for patients with AIDS treated with zidovudine. AB - Bone marrow suppression and anemia are frequent side effects of treatment of the acquired immunodeficiency syndrome (AIDS) with zidovudine (formerly azidothymidine [AZT]). We conducted a randomized, double-blind, placebo controlled clinical trial of recombinant human erythropoietin (100 U per kilogram of body weight thrice weekly by intravenous bolus) in 63 patients with AIDS treated with zidovudine (29 in the erythropoietin group and 34 in the placebo group). Reductions in the number of units of red cells transfused and the number of patients given transfusions per month became apparent in the second and third months of the trial. The reductions were observed in patients with endogenous erythropoietin levels less than or equal to 500 IU per liter at base line, but not in patients whose levels were greater than 500 IU per liter at the beginning of the study. Although the hematocrit and hemoglobin level were not used as the primary criteria of efficacy because the patients received transfusions when their physicians decided that they needed them, a significantly higher rate of increase in the hematocrit was observed in the patients treated with recombinant human erythropoietin whose levels of endogenous erythropoietin were less than or equal to 500 IU per liter (0.00353 points per week) than in the patients given placebo (0.00116 points per week). This effect was not seen in patients with higher levels of endogenous erythropoietin. Serious side effects did not occur more often in the group treated with erythropoietin than in the placebo group. We conclude that recombinant human erythropoietin may be useful in patients with AIDS treated with zidovudine, although the indicators for its use remain to be clarified. PMID- 2186274 TI - The effect on test ordering of informing physicians of the charges for outpatient diagnostic tests. AB - We studied the effect of informing physicians of the charges for outpatient diagnostic tests on their ordering of such tests in an academic primary care medical practice. All tests were ordered at microcomputer workstations by 121 physicians. For half (the intervention group), the charge for the test being ordered and the total charge for tests for that patient on that day were displayed on the computer screen. The remaining physicians (control group) also used the computers but received no message about charges. The primary outcomes measured were the number of tests ordered and the charges for tests per patient visit. In the 14 weeks before the study, the number of tests ordered and the average charge for tests per patient visit were similar for the intervention and control groups. During the 26-week intervention period, the physicians in the intervention group ordered 14 percent fewer tests per patient visit than did those in the control group (P less than 0.005), and the charges for tests were 13 percent ($6.68 per visit) lower (P less than 0.05). The differences were greater for scheduled visits (17 percent fewer tests and 15 percent lower charges for the intervention group; P less than 0.01) than for unscheduled (urgent) visits (11 percent fewer tests and 10 percent lower charges; P greater than 0.3). During the 19 weeks after the intervention ended, the number of tests ordered by the physicians in the intervention group was only 7.7 percent lower than the number ordered by the physicians in the control group, and the charges for tests were only 3.5 percent lower (P greater than 0.3). Three measures of possible adverse outcomes--number of hospitalizations, emergency room visits, and outpatient visits during the study period and the following six months--were similar for the patients seen by the physicians in both groups. We conclude that displaying the charges for diagnostic tests significantly reduced the number and cost of tests ordered, especially for patients with scheduled visits. The effects of this intervention did not persist after it was discontinued. PMID- 2186275 TI - Shattuck lecture--healing and heroism. PMID- 2186276 TI - A randomized, controlled trial of a geriatric assessment unit in a community rehabilitation hospital. AB - We conducted a randomized trial in a community rehabilitation hospital to determine the effect of treatment in a geriatric assessment unit on the physical function, institutionalization rate, and mortality of elderly patients. Functionally impaired elderly patients (mean age, 78.8 years) who were recovering from acute medical or surgical illnesses and were considered at risk for nursing home placement were randomly assigned either to the geriatric assessment unit (n = 78) or to a control group that received usual care (n = 77). The two groups were similar at entry and were stratified according to the perceived risk of an immediate nursing home placement. After six months, the patients treated in the geriatric assessment unit had significantly more functional improvement in three of eight basic self-care activities (P less than 0.05). Those in the lower-risk stratum had significantly more improvement in seven of eight self-care activities. Both six weeks and six months after randomization, significantly more patients treated in the geriatric assessment unit than controls (79 vs. 61 percent after six months) were residing in the community. During the year of follow-up, the control patients had more nursing home stays of six months or longer (10 vs. 3; P less than 0.05). However, there was no difference between the groups in the mean number of days spent in health care facilities (acute care hospital, nursing home, or rehabilitation hospital). Survival analysis showed a trend toward fewer deaths among the patients treated in the geriatric assessment unit, and mortality was significantly reduced in the patients considered to be at lower risk of immediate nursing home placement (P less than 0.05). We conclude that the treatment of selected elderly patients in a specialized geriatric rehabilitation unit improves function, decreases the risk of nursing home placement, and may reduce mortality. The beneficial effects on mortality and function appear greatest for patients at a moderate rather than high risk of nursing home placement. PMID- 2186277 TI - Intraosseous infusion. PMID- 2186278 TI - AIDS dispute. Time not right for Gallo. PMID- 2186279 TI - Cytoskeletal similarities. PMID- 2186280 TI - Protein instruction. PMID- 2186281 TI - Probing the calcium-induced conformational transition of troponin C with site directed mutants. AB - The contraction of skeletal muscle is regulated by calcium binding to troponin C (TnC). TnC consists of two spatially independent domains, each of which contains two metal ion binding sites. Calcium binding to the regulatory sites of the N terminal domain triggers muscle contraction by a series of conformational changes. Site-directed mutagenesis offers a means of elucidating the links in this signal path between TnC and actin-myosin crossbridges. Such mapping is possible if the mutants shift the equilibrium between 'on' and 'off' states of the regulatory complex while maintaining the coupling between calcium binding and tension development. Candidate amino-acid residues for yielding this information would be in positions remote from the calcium-binding sites and from the site of development of tension. Analysis of the crystal structure of TnC and of the model of the calcium-activated molecule has enabled us to identify two such residues: Glu 57 and Glu 88. In separate experiments we have replaced each of these residues by lysines. The resulting reduction in calcium affinity indicates that these residues have a long-range effect on calcium binding. This result may reflect the formation of a salt bridge between positions 57 and 88 that is not present in the native molecule. Moreover, the level of tension recovery when the mutants are incorporated into muscle suggests that the interaction between TnC and other muscle components has also been altered. Thus, these residues may participate in the contraction signal transmission. PMID- 2186282 TI - Conflict of interest case shakes NIH. PMID- 2186283 TI - [Quality of life in therapy evaluation in oncology]. PMID- 2186284 TI - [Premenstrual syndromes]. PMID- 2186285 TI - [Experiences with computer simulation of (ENT) patients]. PMID- 2186286 TI - [Echographic study of the shoulder]. PMID- 2186287 TI - [Symptoms, frequency and severity of hypoglycemia: differences between human and animal insulin?]. PMID- 2186288 TI - [Compression therapy using elastic stockings]. PMID- 2186289 TI - [First aid in reactions to contrast media]. PMID- 2186290 TI - Determining the cause of dementia. AB - In conclusion, dementia remains a major health problem among the elderly. Although Alzheimer's disease is now recognized as the major cause of dementia, there exist many other conditions which can be easily confused with Alzheimer's disease and for which specific treatment is available. Despite inherent problems in clinically diagnosing Alzheimer's disease, a careful and organized approach to the evaluation of the dementia patient will usually allow the clinician to determine the specific cause of the dementia and with a fairly high degree of accuracy. PMID- 2186291 TI - [Histological diagnosis of brain tumors: (9) Dermoid, epidermoid]. PMID- 2186292 TI - [A case of lymphocytic adenohypophysitis associated with sarcoidosis of the lung and eye]. AB - Lymphocytic adenohypophysitis is considered to be an inflammatory disease of the adenohypophysis that is commonly present with visual disturbance and hypopituitarism. Its etiology remains unclear but it is often related to an autoimmune disorder involving other organs, such as the thyroid, parathyroid, or adrenal glands. We encountered a rare case of lymphocytic adenohypophysitis associated with sarcoidosis of the lung and eye during the follow-up period. A 23 year-old woman was hospitalized in July 1986, with a one-month history of headache and visual disturbances which began three days after her second normal delivery. On admission, she showed slight visual impairment and had a left temporal superior quadrantanopia. Endocrinological evaluation revealed thyroid and adrenal hypofunction, and low response of human growth hormone to the loading test. A skull X-ray showed normal shaped sella with some erosion of the dorsum. CT scan showed a rounded contrast-enhanced intrasellar mass extending into the suprasellar cistern. MRI (SR: 500/30) showed a homogeneous low intensity mass which contained a small high intensity area on the relative T2-weighted image (2000/50). A biopsy was performed via right frontotemporal craniotomy. The consistency of the resected tissue was firmer than that of pituitary adenoma. Histologically, the tissue showed diffuse lymphocytic infiltration with some normal adenohypophysis. Her postoperative course was uneventful and the visual impairment improved two months later after the operation. Six months after the operation, she was readmitted with complaints of general fatigue and breathlessness. Chest X-ray showed diffuse infiltration throughout both lung fields, but there was no bilateral hilar lymphadenopathy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186293 TI - [Skullbase-penetrating injuries caused by umbrella tips: case reports]. AB - Two cases of skullbase-penetrating injuries caused by umbrella tips are reported. Case 1: 24-year-old male. Admitted with disturbance of consciousness, left hemiparesis, nasal bleeding, and laceration of left lower eyelid because of having been stabbed by an umbrella tip. Pupils and fundi revealed no definite findings. Plain skull X-ray showed turbid ethmoid sinus and fracture of planum sphenoidale. Cranial CT showed right putaminal hematoma with intraventricular hemorrhage and pneumocephalus. Increased ICP necessitated surgery two days after the injury. Dural laceration of planum sphnoidale, laceration of left optic nerve, right rectal gyrus contusion and rebleeding from the right lenticulostriate branch were observed. Dural plasty and removal of hematoma with external decompression were carried out. He had a good postoperative course, but left visual loss and left hemiparesis remained. Case 2: 29-year-old male. Admitted with excoriation of his right nostril because of having been stabbed by an umbrella tip, severe headache, and nasal discharge. Oculomotor palsy was observed as well as CSF rhinorrhea and meningeal irritability. Plain skull X-ray showed niveau in sphenoidal sinus, pneumocephalus, and fracture of sella turcica. His complaint disappeared after conservative therapy. We reviewed the literature and found only 4 similar cases. The skullbase, because of its anatomical character, is likely to be penetrated in orbital and periorbital injury caused by umbrella tips. Cases which include disturbance of consciousness have a poor prognosis. We hope the fact that umbrella tips can easily become life-threatening objects will come to the attention of the general public so that similar cases may be avoided. PMID- 2186294 TI - [An autopsy case of primary intracranial squamous cell carcinoma]. AB - An autopsied case of primary intracranial squamous cell carcinoma (PISCC) is reported, and 25 previously reported cases of PISCC, followed by the Garcia's criteria, are reviewed. A 72-year-old female was admitted to our service with chief complaints of headache and nausea on March 30, 1988. She had no neurological deficits on admission. However, CT examination revealed a round mass lesion in the left hypothalamus with dislocation of the brain stem. The cerebrospinal fluid (CSF) examination showed squamous cell carcinoma cytologically, and slightly higher levels of beta-HCG (13.0 ng/ml) and CEA (14.2 ng/ml). Because of progressive worsening in the level of her consciousness, total removal of a suprasellar tumor was performed on April 19, 1988. Gross appearance of the tumor was yellowish, soft and encapsulated. Histologically, it was squamous cell carcinoma. She did well for several days after the operation, then deteriorated. Finally she expired because of dissemination of the carcinoma on May 14, 1988. Postmortem examination revealed a large mass of squamous cell carcinoma in her right cerebellopontine angle. Except for that in the brain, no cancer was found in her body. Immunohistological study of the tumor specimen demonstrated positive for HCG in some of the large-sized neoplastic cells. Twenty six cases of PISCC have been reported previously, so far. However, 21 cases out of the 26 PISCC were thought to have originated from intracranial epidermoid, one from the dermoid and the other one from craniopharyngioma. In the other three cases of PISCC, including the present case, the origin of the tumor was not able to be identified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186295 TI - [Hemorrhoids: current therapeutic directions]. PMID- 2186296 TI - [Infectious endocarditis. Role of surgical therapy]. AB - The problem of infectious endocarditis (IE) is approached through a review of personal experience. The series examined consists of patients, 17 with active and 21 dormant infection. Furthermore 12 in the first group, 18 in the second had natural heart valves, while 5 in group I, 3 in group II had been given artificial ones. After an analysis of the aetiopathogenic, clinical and diagnostic aspects of the condition with emphasis on the fact that Staphylococcus aureus is currently more responsible for infections in natural valves and the epidermidis for acute prosthesis infections which have a higher early and late mortality rate (40% in hospital, 33.3% long-term), the paper discusses the criteria for surgical intervention. In line with opinions expressed in the literature, it is pointed out that, while the patient's haemodynamic status is certainly the main criterion for any decision, other factors such as embolism, impaired conduction, kidney failure and expansion of the infection to contiguous tissues, should not be under estimated. PMID- 2186297 TI - [La Peyronie's disease. Our experience]. AB - Following an aetiopathogenetic review of I.P.P., diagnostic and therapeutic possibilities are assessed. Medically, stress is laid on the value of orgotein, an SOD which, used in time, reduces pain and penis curving and permits satisfactory sexual activity. In the case of inveterate forms or of large plaques, the use of a silastic prosthesis is proposed. This support enables a normal sex life to be continued, so resolving psychological and family stress. PMID- 2186298 TI - [Frequency and clinical significance of ectopic pancreas]. AB - Ten cases of ectopic pancreas are presented. The literature on the subject is reviewed and the more controversial aspects of the disorder are discussed, in particular the clinical and anatomic-pathological significance, its diagnostic recognition, and the necessary treatment. PMID- 2186299 TI - [Parietal damage in intestinal infarction. Clinical and anatomo-pathological considerations]. AB - The physiopathology of parietal damage due to acute ischaemia is reviewed on the basis of a personal series of more than 70 cases. The reported data (not particularly abundant) is examined and an attempt made to draw conclusions that, free from mere theoretical and abstract value, may materially help the surgeon in his by no means easy decision to revascularize or resect an intestinal segment. PMID- 2186300 TI - [Foreign bodies in the alimentary tract. Surgical treatment]. AB - Gastro-intestinal foreign bodies are a by no means rare event in surgery and in the USA mortality is about 1500 people per annum. The surgical treatment of foreign bodies in the alimentary tract is reported here. Certain cases of voluntary ingestion in mental patients are reported, comparing personal experience with the data reported in the literature. PMID- 2186301 TI - [Primary carcinoma of the gallbladder]. AB - Primary carcinoma of the gallbladder, while infrequent, is the most representative among the malignant neoplasms of the biliary tract. The diagnosis of carcinoma of the gallbladder was made in 22 out of 1252 operations performed for gallbladder disease (1.8%) since January 1980 through June 1988: only in 9% of the subjects a malignant tumor of the gallbladder was suspected preoperatively. In 21 cases the carcinoma was associated with chronic lithiasic cholecystitis. The 22 cases were assessed according to the classification proposed by Nevin. The operations performed were: 4 routine cholecystectomies (stages I and II) 4 cholecystectomies with lymphadenectomy (stages I and II); 4 cholecystectomies with lymphadenectomy and liver wedge resection of the bed of the gallbladder (stages II, III, IV, V); 7 explorative laparotomies and 3 gastrojejunal anastomoses (stage V). A complete follow-up was available for each of the 22 subjects: cumulative survival rates were calculated according to Kaplan Meyer. The overall 5-year cumulative survival rate after operation was 19% for the whole group, whereas it reached 76% for the subgroup of 9 patients classified in stages I and II. This analysis reinforces the statement that surgical therapy can achieve excellent results if brought about before cancer overwhelms the muscular layer of the gallbladder wall. Thus, as the preoperative diagnosis of gallbladder carcinoma is extremely difficult and uncertain, any delay in performing cholecystectomy seems to be unwise in all those cases of chronic benign disease of the gallbladder (whether lithiasic in nature or not) that are suspected to be a major risk factor for cancer degeneration because of their frequent association with the carcinoma of the gallbladder. PMID- 2186302 TI - [Acute cholecystitis: surgical treatment]. AB - Personal experience in the observation of 177 patients suffering from acute cholecystitis and treated in the five-year period 1981-1985 is reported. In particular, problems related to surgical treatment are pointed out. PMID- 2186303 TI - [Rare primary hepatic neoplasms. Our experience in 2 cases: a primary lymphoma and a leiomyosarcoma of the liver]. AB - In a review of personal experience of major liver surgery, 2 very rare cases of primary liver tumours, one lymphoma and one leiomyosarcoma are presented. The world literature on the subject is also reviewed and follow-up results are reported after indicating the surgical techniques adopted. PMID- 2186304 TI - [De-nol in NSAID-induced gastroduodenal lesions]. AB - It is well known that prolonged use of Non Steroidal Anti-inflammatory Drugs (NSAIDs) can trigger gastroduodenal lesions and/or their complications, even in the absence of any dramatic painful and dyspeptic symptomatology. The paper reports the results of a double-blind study carried out with Colloidal Bismuth Subcitrate (CBS, DE-NOL), an antiulcer drug with cytoprotective activity, versus ranitidine (RN) with the aim of assessing its therapeutic efficacy in promoting healing of either gastric or duodenal ulcers induced by NSAIDs. It is concluded that the efficacy of DE-NOL is comparable to that of RN, although some minor differences in healing rates were observed: these being in favour of DE-NOL in the gastric ulcer patients and in favour of RN in the duodenal ulcer patients, respectively. In addition, it is stated that in patients undergoing chronic treatment with NSAIDs the use of cytoprotective drugs as a preventive treatment as well as periodic endoscopic surveillance are more useful and rational in order to combat the onset of NSAIDs-induced side-effects, given the frequent paucity of symptomatology following the occurrence of gastroduodenal lesions. PMID- 2186305 TI - [Infectious complications of LeVeen peritoneovenous shunt. Description of a case]. AB - A lethal case of E. coli induced meningitis and sepsis in patient with Le Veen peritoneo-venous shunt (PVS) for refractory ascites during alcohol induced cirrhosis of the liver is reported in confirmation of the high number of infectious complications that affects the cirrhotic, especially if he has been subjected to PVS. This report owes its interest to the unusual site of the infection which is however fairly frequent in these particular patients. PMID- 2186306 TI - [Echographic findings in a case of gastric leiomyoblastoma]. AB - Gastric leiomyoblastoma is a rare stomach tumour arising in the muscular tunica. Its prevalently oesophytic development makes diagnostic techniques that mainly concentrate on the intestinal lumen (digestive X-ray and endoscopy) of little use. A case is reported in which echography pointed diagnosis in the right direction by analysing a number of typical symptomatological signs. PMID- 2186307 TI - [Echographic evaluation of the endometrium after multifollicular ovarian stimulation with gonadotropin]. AB - The Authors report 15 pregnancies obtained by multifollicular ovarian stimulation with gonadotropins. They have used only the utero-ovarian echographic monitoring for ovarian response surveillance, for the timing of hCG administration and for a prognostic judgement of the pregnancy outcome. PMID- 2186308 TI - [Extrauterine pregnancy. Critical review of the clinical diagnosis and early echography]. AB - A case of extrauterine pregnancy is reported. After a short review of the literature on the subject, personal experience of early diagnosis is reported and importance is attributed in IUD carriers to menstrual dysrhythmia and pelvic pain. For correct early diagnosis, such symptomatology must be integrated with laboratory tests and pelvic echography. PMID- 2186310 TI - The influence of dietary fat on carcinogenesis: lessons from experimental models. AB - Recent studies of the effects of dietary fat on experimental carcinogenesis have probed the influence of the dietary fat source, the time during carcinogenesis when a high-fat diet is fed, the interactions between fat and calories, and the potential mechanisms for the observed effects of fat on cancer. The essential fatty acids in the fat, the degree of their unsaturation, and the location of the unsaturation are all important in determining the influence of a dietary fat source on carcinogenesis. In addition, alterations in dietary fat can modify various sites and forms of cancer differently. Dietary fat has been clearly shown to be important in the promotion of cancer, and recent studies indicate that dietary fat can also be a factor in the initiation of cancer. Although the calories contributed by a high-fat diet also factor into cancer enhancement, dietary fat appears to contribute more than its high-caloric density. One potential mechanism for the influence of dietary fat on carcinogenesis is through modulating the activation of protein kinase C. PMID- 2186309 TI - Two types of motor rhythm induced by NMDA and amines in an in vitro spinal cord preparation of neonatal rat. AB - Rhythmic motor activities were studied in two rat spinal cord preparations; in the first one, the spinal cord was completely isolated and the ventral roots activity was recorded; in the other, spinal cord and hindlimbs were kept in order to record muscle activities. Motor patterns were therefore recorded in ventral roots and/or hindlimb muscles. Two kinds of specific patterns were elicited by neurochemicals. The first which was induced by N-methyl-D,L-aspartate (NMDA) and serotonin (5-HT) was a slow rhythm (0.5-0.2 Hz) of left and right alternating bursts of spikes. The second one which was induced by NMDA, 5-HT and norepinephrine (NE), was a high frequency rhythm (5-10 Hz). One particularity observed was that these two rhythms could occur simultaneously. The relationship between the two in vitro rhythms is discussed and they are compared with those reported in other rhythmic systems. PMID- 2186311 TI - Evidence for an association between periconceptional use of multivitamins and neural tube defects. PMID- 2186312 TI - Evidence against an association between periconceptional use of multivitamins and neural tube defects. PMID- 2186313 TI - Zinc and copper wastage during acute diarrhea. PMID- 2186314 TI - Phosphatidylcholine, lysophosphatidylcholine, and lipoprotein secretion by choline-deficient hepatocytes. PMID- 2186315 TI - Dietary fat and tumor metastasis. AB - Evidence from several types of studies indicates a relationship between fat intake and occurrence of malignant tumors at specific sites. When rodents are fed high-fat diets, the incidence of mammary tumors sharply increases and latency of tumor appearance is greatly diminished, as compared with the same parameters in animals fed low levels of fat. Despite advances in surgical technique and the development of aggressive therapies for the treatment of primary cancers, most deaths in humans with cancer are caused by metastasis. Accordingly, we have reviewed the process of metastasis and have focused on the question of whether dietary fat can play a role. Metastasis is a complex, multistep, progressive process, and dietary fats may affect specific events such as implantation, survival, and proliferation of tumors. Finally, we discuss possible mechanisms by which dietary fat can modulate metastasis. Available data lead us to stress the importance of assessment of metastasis in studies of the effects of dietary fat on tumorigenesis. PMID- 2186316 TI - Congenital depression of the fetal skull. AB - One hundred forty-seven cases of congenital skull depression are analyzed, including two presented by the authors, and a review of the literature follows. A management plan emphasizing a conservative approach is outlined. PMID- 2186317 TI - Pregnant patients, painful legs: the obstetrician's dilemma. PMID- 2186318 TI - [Diabetes mellitus and breast cancer. A retrospective follow-up study]. AB - The influence of diabetes mellitus on the course of breast cancer was investigated retrospectively in 752 patients. Possible unfavourable prognostic factors like overweight, lipid disorders, age and menopausal status were considered as confounders in a Cochran-Mantel-Haensel analysis. There was no difference in primary tumor status and lymph node involvement between patients with diabetes mellitus and nondiabetic patients. Diabetic patients had more often overweight, lipid disorders and were older than nondiabetic patients. Metastatic disease was highly significant correlated with primary tumor status (p less than 10(-6)) lymph node involvement (p less than 10(-10)) and diabetes mellitus (p less than 10(-5)). Overweight, lipid disorders, age and menopausal status were not correlated with metastatic disease. A possible explanation of the correlation between diabetes mellitus and metastatic disease could be hyperinsulinism in type IIB diabetes. A type IIB diabetes in most of the patients included in this study is very plausible because of the correlation between overweight, lipid disorders, old age and diabetes mellitus. This type of diabetes is characterised by a relative resistence to insulin in the target tissues and a prolonged and exceeding insulin secretion. Experimental data demonstrate that insulin stimulates the growth of breast cancer cell in vivo and in vitro. PMID- 2186319 TI - [Steroid hormone receptor status of colorectal cancers]. AB - Tumor samples of 26 consecutive colorectal carcinomas were studied for the presence of steroid hormone receptors for estrogen and progesterone. In all cases, the estradiol receptor binding capacity was below 2 fmol/mg cytosol protein. In 4 of 26 samples, progesterone receptor levels from 13 to 23 fmol/mg cytosol protein were observed. Because of the identification of steroid receptors in some cases and single reports in literature about tumor regression under hormone therapy of colorectal carcinoma, further investigations seem indicated to study the hormone sensitivity of colorectal carcinoma. PMID- 2186320 TI - Randomized clinical trial comparing mitoxantrone with epirubicin and with doxorubicin, each combined with cyclophosphamide in the first-line treatment of patients with metastatic breast cancer. AB - Two hundred and twenty-four patients with advanced breast cancer were enrolled in a multicenter prospective randomized clinical study and received either doxorubicin (40 mg/m2), or epirubicin (40 mg/m2) or mitoxantrone (12 mg/m2) each combined with cyclophosphamide (600 mg/m2) i.v. In the patient collective the following response rates were observed: complete response 12.1%; partial response 30.6%; stable disease 40.5%; progressive disease 16.8%. A complete response was observed significantly less often in patients where more than one organ site was involved as compared to those patients with only one metastatic site. The mean time period required to reach a best response was 3.7 months. There was no significant difference between the response rates in the three arms. In comparing the observed toxicities in 1,434 treatment cycles, there was a significant difference with regard to leukocytopenia (mitoxantrone arm exhibiting more than either epirubicin and doxorubicin) although infections did not occur more frequently in the mitoxantrone arm; with regard to alopecia, mitoxantrone and epirubicin arms both exhibited less than doxorubicin. It is noteworthy that no patient who had previously received adjuvant chemotherapy achieved a complete response (p = 0.006). The overall significance of these findings can only be clearly evaluated when survival times can be measured. PMID- 2186321 TI - Sequential versus alternating chemotherapy for high-grade non-Hodgkin's lymphomas: preliminary results of a phase III multicentre trial. AB - In a multicentre phase III trial 105 previously untreated patients with high grade non-Hodgkin's lymphomas stage II-IV were randomized to receive either 4 cycles of CHOEP (cyclophosphamide 750 mg/m2 i.v. day 1, doxorubicin 50 mg/m2 i.v. day 1, vincristine 2 mg i.v. day 1, etoposide 100 mg/m2 i.v. days 3-5, prednisolone 100 mg p.o. days 1-5) (treatment arm A), or 4 cycles of chemotherapy with hCHOP (cyclophosphamide 1,200 mg/m2 i.v. day 1, doxorubicin 40 mg/m2 i.v. days 1 + 2, vincristine 2 mg i.v. day 1, prednisolone 100 mg p.o. days 1-5) alternating with IVEP (ifosfamide 1,500 mg/m2 i.v. days 1-5, vindesine 3 mg/m2 i.v. day 1, etoposide 120 mg/m2 i.v. days 3-5, prednisolone 100 mg p.o. days 1-5) in treatment arm B. After 4 cycles of chemotherapy an involved field irradiation with a total dose of 35 Gy was given to all patients demonstrated to be in complete or partial remission without persisting extranodal disease. A complete response (CR) was seen in 86/105 patients (82%) with 88% CR in arm A vs. 76% CR in arm B. During a median follow-up of 11 months (range 2-31 months) 13 patients relapsed (6 patients arm A, 7 patients arm B). The overall survival at 30 months is projected to be 72% vs. 83% for arm A and B respectively. Disease-free survival is projected to be 78% in arm A and 45% in arm B at 28 months. So far, the differences in CR, survival and disease-free survival are not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186322 TI - Recombinant human granulocyte-macrophage colony-stimulating factor and low-dose cytosine-arabinoside in the treatment of patients with myelodysplastic syndromes. A phase II study. AB - As part of a multicenter trial 12 patients with myelodysplastic syndromes (MDS) were treated with 14-day-cycles of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 250 micrograms/m2 day s.c.). In addition, all patients received 20 mg/m2/day s.c. cytosine-arabinoside (Ara-C) 12 h after GM-CSF except for patients suffering from refractory anemia (RA) according to FAB classification. Courses were repeated after 4 weeks. In 11 evaluable patients, results according to FAB-classified MDS were as follows: RA, 1/2 response (R), 1/2 stable disease (SD); RAEB, 2/3 R, 1/3 SD; RAEB-T, 1/6 CR, 1/6 PR, 2/6 R, 2/6 progression; CMML, 1/2 SD. In 2 patients with RAEB-T, overt acute myeloid leukemia was observed 2 and 10 weeks after initiation of treatment. With few exceptions, treatment resulted in a prompt increase in granulocytes and eosinophiles. This was associated with improvement of infectious complications. Increases in red cells and platelets occurred variably and was apparently associated with responses of the underlying disease. Dose limiting side effects consisted of fever, severe fatigue and dolent local reactions at the site of GM CSF injection. In addition, nausea and diarrhoea occurred frequently. Less often, respiratory and cardiovascular side effects were encountered. In summary, GM-CSF +/- Ara-C in MDS results in objective remission with manageable toxicity. Conceivably, this regimen will serve as a base for future treatment strategies against MDS. PMID- 2186323 TI - Interventional antimicrobial strategy in febrile neutropenic patients. Results of a multicenter study in 1,260 patients with hematological malignancies. The Interventional Antimicrobial Strategy Study Group, Paul Ehrlich Society for Chemotherapy. AB - In a prospective, randomized multicenter trial of the Paul Ehrlich society different concepts for sequential empirical antimicrobial strategy for the treatment of patients with neutropenia less than 1.0/nl and fever greater than 38.5 degrees C and/or documented infection were studied. In phase I, patients with unexplained fever (FUO) were randomized for the combination of acylaminopenicillin plus aminoglycoside or third-generation cephalosporin plus aminoglycoside or double beta lactam therapy. Non-responders received additional vancomycin or all three substances of phase I in phase II. In phase III, all patients with persistent fever were then treated with amphotericin B plus 5 flucytosine and rifampin and randomized for the continuation of the double beta lactam regimen or additional imipenem/cilastatin. 667 (52.9%) of 1260 evaluable patients had FUO during the whole study period, of which 62.5% could be cured in phase I, 43.2% of non-responders in phase II and 55% of persistently febrile patients in phase III. The overall rate of complete response was 79.5%. 2.8% were non-responders, 11.7% were not evaluable for response and 40 patients (6%) died during the study, 24 (60%) of whom due to the underlying disease or the toxicity of antileukemic therapy. A significant difference between the treatment groups could not be detected in either of the three study phases. PMID- 2186324 TI - Melphalan and prednisone (MP) versus vincristine, BCNU, adriamycin, melphalan and dexamethasone (VBAMDex) therapy for multiple myeloma. Early results of a multicenter trial. The German Myeloma Treatment Group. AB - 136 untreated multiple myeloma patients of stage II and III were collected in the study. 37/51 stage II patients had progressive disease and were treated with melphalan and prednisone (MP). 85 patients were of stage III and randomized into MP and vincristine, BCNU, adriamycin, melphalan and dexamethasone (VBAMDex) treatment groups. 55% of MP treated patients responded versus 75% of the VBAMDex group. Since the study has been activated only 16 months ago, no difference in survival could be observed. PMID- 2186325 TI - [Erythropoietin treatment of tumor-associated anemia in patients with multiple myeloma]. AB - Anemia of malignancy is a complication of neoplastic disease which causes impairing symptoms and often requires blood transfusions. In this clinical trial, we have treated 13 patients suffering from chronic anemia of malignancy and multiple myeloma with recombinant human erythropoietin (rHuEPO) three times a week. Eleven patients responded to the treatment by appropriate increases of their hemoglobin levels and the eventual correction of the anemic state, one non responding patient had to terminate the treatment early because of transfusion requirements. Under rHuEPO therapy, the evaluated parameters of iron metabolism indicated the enhanced synthesis of hemoglobin. The symptoms of anemia subsided in the responding patients and most of them reported a hightened subjective sense of well-being. No adverse side effects, particularly no episodes of hypertension, were observed in any patient. PMID- 2186326 TI - [Fotemustine, a new nitrosourea derivative. Current status of development]. AB - Fotemustine is a new chloronitrosourea recently developed by the French company Servier. It is chemically characterized by the graft of an aminophosphonic acid on the chloronitrosourea radical, which makes it highly lipophil. The preclinical studies revealed a lower mutagenicity and hepatotoxicity when compared to BCNU. The pharmacokinetic studies showed a high body clearance and a short half-life. The phase I study enabled us to determine the definitive treatment schedule: 100 mg/m2/week during 3-4 consecutive weeks followed by 5 weeks' rest and a maintenance therapy of 100 mg/m2 every 3 weeks for stabilized or responding patients. Fotemustine should be given as a 1-h intravenous infusion, protected from daylight. There was no life-threatening toxicity and positive activity was observed in different tumors and especially melanomas. This indication was thus chosen for the phase II study. Among the 153 evaluable patients, the response rate reached 24.2%. It depended on the location of the metastatic sites, with 25% brain metastases, 19.2% visceral metastases, 8.8% liver metastases and 31.8% skin and lymph node metastases. The median duration of response was 22 weeks. The median overall survival of responding patients reached 85 weeks, while it dropped to 52 weeks in case of minor response or stabilization and 17 weeks in case of progression. The hematological toxicity was moderate (WHO grade III and IV: 46.3% leukopenia and 40.3% thrombopenia) and delayed as for other nitrosoureas (nadir: white blood cells: day 44 and thrombocytes: day 35).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186327 TI - Plastic injection method for preparing microvascular corrosion casts for SEM and its practical application. AB - This paper examines the application of the acryl plastic injection to the preparation of vascular corrosion microcasts for scanning electron microscopy (SEM). The original injection method using acryl plastic was described by Taniguchi, Ohta et al. in 1952 and 1955, under the title of "New improved method for injection of acrylic resin". Three dimensional observations were undertaken in our laboratory on the angiology at the macro- and microscopic levels of various organs from various mammals employing the original method. Based on this extensive experience, an injection method for preparing corrosion microcasts for use in SEM was devised in our laboratory. Microcasts prepared by the present method were able to demonstrate the fine vascular architecture of each organ. In general, although applications for preparing vascular microcasts of isolated and parenchymal organs are not so difficult, the method can be used to be applicable for demonstrating the fine vascular architecture related to or within hard tissues, as well as for investigating the morphological relations between changes of vascular patterns and restorative changes in the surrounding tissues affected by experimental operations. SEM microphotographs are also presented to illustrate actual practical applications. PMID- 2186328 TI - An autopsy case of azygos lobe and the extra-pulmonary course of the bronchial veins in man. AB - The present case represents the second report of an aberrant azygos lobe, following Adachi's (1940) first case. The authors describe the characteristic features of an azygos lobe observed in the right lung of a 65-year-old man as well as the extra-pulmonary course of the bronchial arteries and veins. The literature on the azygos lobe reported in Japan and the extremely rare cases in which an azygos lobe has been found on the left side, are summarized. Upon dissecting the pulmonary parenchyma, it became clear that the azygos lobe was supplied by definitive segmental branches (B1a and B2a, A1a and A2a, and V1a and V2a) of the tracheobronchial tree and pulmonary vessels. The authors review and summarize the patterns of the segmental bronchi and vessels in the azygos lobe and also discuss the development of this anomaly. PMID- 2186329 TI - The facial artery of the lion (Panthera leo). AB - An investigation was made of the facial artery in 3 heads of the lion (Panthera s. Felis leo) in the possession of the authors' department. The heads were injected with acryl plastic via the common carotid artery and were examined from the standpoint of the comparative anatomy. Five sides of these 3 heads were prepared to vascular corrosion casts and the remaining side to a dessection specimen preserved in formalin solution. The facial artery of the lion arose independently from the anteroinferior wall of the external carotid artery between the styloglossus and digastricus muscles and between the origins of the lingual and the posterior auricular arteries at a position where the external carotid curved laterally anterior to the tympanic bulla. The facial artery gave rise to the mandibular glandular branch posterosuperiorly immediately after its origin and passed forwards medial to the insertion of the masseter along the superior margin of the digastricus and bent anteroinferiorly giving off the sublingual glandular branch after the divergence of a thick, masseteric branch. The facial artery reached the posterior margin of the mylohyoideus muscle, where it gave rise to the submental artery anteroinferiorly from its inferior wall. The submental artery passed forwards along the inferior margin of the mandible, giving off the digastric and the mylohyoid branches, up to the intermandibular synchondrosis, where it anastomosed with the opposite fellow after giving off the genioglossal branch. The main stream of the facial artery, after giving off the submental artery, reached the face through the facial vascular notch of the mandible. The facial artery passed anterosuperiorly along the anterior margin of the masseter muscle, giving off the buccal, the cutaneous and the mandibular marginal branches, up to a position posterior to the oral angle, where it terminated to the inferior labial and the posterior superior labial arteries. Similarities between the lion and the cat were found in terms of both the origin and ramifications. However, the inferior labial artery was more developed than that of the cat, whereas the peripheral ramifications of the submental artery were underdeveloped and supplemented by the lingual artery. PMID- 2186330 TI - How the golden egg of Medicare is cooking ophthalmology's goose. PMID- 2186331 TI - The ocular effects of intracarotid bromodeoxyuridine and radiation therapy in the treatment of malignant glioma. AB - Since July 1985, 23 patients have been entered into a phase I/II clinical trial using intraarterial 5-bromodeoxyuridine (BUdR) (400-600 mg/m2 daily for 8.5 weeks) and focal external beam radiotherapy (59.4 Gy at 1.8 Gy daily in 6.5 weeks) in the treatment of malignant gliomas (Kernohan grades 3 and 4). The side effects in all patients have included varying degrees of anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, and conjunctivitis. Mucopurulent conjunctivitis and exposure keratitis developed in several patients and spontaneous corneal perforation developed in one. Eyes from two individuals examined at autopsy showed significant changes. Animal studies that predated clinical trials using rhesus monkeys did not predict the ophthalmologic complications seen in human subjects. PMID- 2186332 TI - Pathology of the thyroid and parathyroid glands. AB - Open communication between surgeon and pathologist is key in the area of thyroid and parathyroid pathology. Gross and microscopic examination provides valuable data, including important prognostic information, to guide further clinical management. A number of new techniques are being developed. These will not only enable us to learn more about the pathogenesis of lesions in these organs but may provide additional prognostic data. PMID- 2186333 TI - Needle aspiration biopsy of the thyroid and parathyroid. AB - Aspiration biopsy is the most definitive diagnostic step in the investigation of thyroid masses. The clear fluid from the rare parathyroid cyst should be sent for parathyroid hormone assay. Guided fine-needle aspiration identifies parathyroid tumors in cases in which reexploration is necessary. PMID- 2186334 TI - Thyroid physiology and immunology. AB - The thyroid gland, like the paintings of Chagall, has forced us to look at our traditional understanding of things in a new way and to gain fresh insight into ancient concepts of human physiology. PMID- 2186335 TI - Recent advances in thyroid imaging. AB - Thyroid imaging has evolved from early radionuclide rectilinear thyroid scanning to the recently developed technique of single photon emission computed tomography. At the same time, x-ray fluorescent scanning, ultrasound, computed tomography, magnetic resonance imaging, and positron emission tomography have improved identification of the thyroid gland. The appropriate use and relative roles of these imaging modalities in the investigation of patients with thyroid disease are discussed. PMID- 2186336 TI - The measurement of DNA content and ploidy analysis in thyroid neoplasms. AB - It is clear that the DNA content of endocrine cells is influenced by factors other than neoplastic change and transformation. Although it can be concluded that, in general, the DNA content of neoplasms is increased, it is less clear whether this increase in DNA content is the cause or the effect of neoplastic transformation. The actual consequences of an increased DNA content are still largely unknown. However, based on a substantial body of data on the measure of nuclear DNA content in thyroid neoplasms, several conclusions appear to be reasonable. First, the measurement of nuclear DNA content and ploidy analysis are not sufficiently reliable parameters upon which to distinguish a benign from a malignant thyroid neoplasm. Therefore, this parameter has failed to live up to the expectation that it would be a powerful diagnostic tool. Second, the measurement of nuclear DNA content is useful after a histomorphologic diagnosis has been made since it correlates very well with the prognosis and clinical outcome of the patient. It is clear that aneuploid thyroid carcinomas are responsible for earlier recurrence, an increased likelihood of distant and diffuse metastases, and an increased incidence of death compared with diploid thyroid carcinomas. Except for the rare occasion, diploidy implies a uniformly long-term survival whereas aneuploidy is associated with a variable clinical course. Irrespective of histomorphology, lethal lesions of the thyroid are invariably aneuploid, whereas lesions associated with prolonged survival or a favorable outcome can be either diploid or aneuploid. Aneuploidy in well differentiated thyroid carcinoma is more likely in older patients, in less well differentiated neoplasms, and in neoplasms infiltrating beyond the thyroid capsule. Age, type of neoplasm, extrathyroidal extension, and recurrent disease all appear to be more important prognostic variables than is nuclear DNA content. However, nuclear DNA content can increase the prognostic power of these variables and consequently may come to be increasingly useful in the management of some patients with thyroid neoplasms. After a histomorphologic diagnosis has been made, the measurement of nuclear DNA content and a determination of the DNA ploidy may have significant prognostic value. PMID- 2186337 TI - The relationship between Hashimoto's thyroiditis, thyroid neoplasia, and primary hyperparathyroidism. AB - The relationship between Hashimoto's thyroiditis and follicular cell carcinoma of the thyroid remains controversial. Hashimoto's thyroiditis is regarded by some as a premalignant lesion for which thyroidectomy is definitely indicated. In contrast, other investigators have found no increased evidence of thyroid carcinoma in patients with this disease. As a result, the management of thyroid nodules in patients with Hashimoto's thyroiditis remains highly individualized. A program for the management of patients with chronic Hashimoto's thyroiditis with co-existing neoplasia or primary hyperparathyroidism is outlined. PMID- 2186338 TI - [Use of New World Saimiri and Aotus monkeys in the development of an anti-malaria vaccine]. AB - Saimiri and Aotus, two neotropical primates, are currently used in different domains of human malaria research. Here we present a simplified and non exhaustive enumeration of different aspects in concern of using these monkeys as experimental hosts, their availability, laboratory-bred animals versus wild caught animals, their potential as experimental model in evaluating anti-malaria vaccine candidates, and some related activities at the Pasteur Institute. PMID- 2186339 TI - [Value of primates for the evaluation of pulmonary pathology]. AB - A delicate but contrived network of tissues adapted to hematosis, handling of mediators and defense toward inhaled xenobiotics makes up the lung. Response to aggression is strongly species dependent. The primate is mostly to be used when disease modeling in animals is needed for direct extrapolation to the human. Most current field of interest includes infectious pathology, respiratory distress and toxico-kinetics modelling of aerosol hazards. PMID- 2186340 TI - [Value of the monkey Papio papio for the study of epilepsy]. AB - The baboon Papio papio is the only animal model showing a natural photosensitive epilepsy very similar to that observed in some human epileptic patients. In the baboon, intermittent light stimulation (ILS) induces bilateral and synchronous myoclonic twitches which are associated with paroxysmal discharges (PDs) predominating in the frontal cortex, and can be followed by generalized tonic clonic seizures. We were able to demonstrate the motor cortical origin of all these manifestations since neuronal generators responsible for paroxysmal discharges are localized there and are activated by visual afferents from the occipital lobe. The corpus callosum is the structure determining the interhemispheric synchronization of PDs. An unbalance of neurotransmitter systems such as GABA or excitatory amino acids should be responsible for the hereditary predisposition of baboons to photosensitive epilepsy. Some Papio papio, either photosensitive or not, may show spontaneous truncular myoclonic twitches, different from those induced by intermittent light stimulation, and resembling the intention myoclonus as observed in some human neurological disorders (post anoxic syndrome, degenerative encephalopathies such as Ramsay-Hunt syndrome...). Because of the absence of any abnormal electrographic discharge, this myoclonus is considered non epileptic. Until now, we were unable to determine the structure generating this myoclonus. The most probable origin is in the lower brain stem. Experimental data suggest that a local unbalance of the cholinergic neurotransmission could be responsible for the predisposition of baboons to show this type of myoclonus. PMID- 2186341 TI - [Primates in studies on the safety of drugs]. AB - Primates are more and more frequently used in the evaluation of the safety aspects of drugs. Because of their similar phylogenic profile, these animals appear to be more predictive than other species (rat, mouse, rabbit or dog) used in toxicological studies. This relationship is confirmed by anatomical, metabolic and physiological observations. Primates are rarely used in teratogenesis studies, because the methods and materials involved are too complex. However, even in these studies, primates appear to be the most predictive species. PMID- 2186342 TI - Major pitfalls in Doppler investigations with particular reference to the cerebral vascular system. Part I. Sources of error, resulting pitfalls and measures to prevent errors. AB - Major pitfalls in Doppler investigations are presented based on 340 evaluated cerebral Doppler examinations in infants. Substantial pitfalls may result from: A. Physics of sound waves and Doppler instruments (errors due to high pass filter cut off, aliasing, rapid image update). B. Quality and adjustment of the Doppler instrument (errors due to low sensitivity, inappropriate adjustment of Doppler controls, inadequate wall filter). C. Examination technique (errors due to an unfavourable angle of incidence or due to transducer-induced pressure: decrease predominantly in diastolic flow velocity-increase in maximum flow velocity in the straight sinus). D. Hemodynamics (errors due to spatial or temporal variations of the flow profile, pulsatility, non-uniform distribution of cerebral blood flow/CBF). E. Cerebral vascular anatomy (errors due to an unfavourable probe position as related to the three-dimensional arrangement of vessels, inadequate separation of closely adjacent vessels). F. Interpretation (flow velocity or Resistance Index/RI is taken to equal CBF, RI is taken to equal peripheral vascular resistance, one artery is taken to represent the cerebral circulation). Pitfalls may be avoided by using adequate means (low wall filter adjustment, high Doppler frequency, critical assessment of velocity spectra) to reduce the likelihood of errors occurring. PMID- 2186343 TI - Pericerebral fluid collections and ultrasound. AB - The authors have studied 142 cases of pericerebral fluid collection, by ultrasound. Three echographic patterns are individualized: anechogenic single compartment (109); thin linear echogenic membrane dividing the pericerebral fluid collection (25); the third group (8) presented with a peripheric echogenic collection. The use of high frequency probes permits the detection of pericerebral effusions, and provides new information about the high incidence. Ultrasound can define the anatomical position and show the complications which are mainly acute subdural hematoma. PMID- 2186344 TI - Laryngeal ultrasonography in infants and children: anatomical correlation with fetal preparations. AB - Normal sonographic anatomy of the larynx in children was established by studying 40 healthy children and 3 fetuses. The normal anatomy is described on transverse sonograms passing at level of the ventricular bands, the true vocal cords and the subglottis and the interpretation of the sonographic aspect of the larynx is given. Ultrasound of the larynx seems to provide a good analysis of cartilaginous and endolaryngeal structures and can also show the dynamic aspect of the larynx. A pathological case is described as an illustration of the potentialities of this new way of imaging the larynx. PMID- 2186345 TI - Variability of clinical presentation of hepatic artery thrombosis in pediatric liver transplantation: role of imaging modalities. AB - Among a series of 90 pediatric liver transplantations, 9 cases of hepatic artery thrombosis (HAT) in 8 patients are reported. All cases were diagnosed in the first two weeks and confirmed angiographically and surgically. Clinical presentation was often unreliable with only 2 cases showing the typical pattern of massive hepatic necrosis. Five cases presented with biliary complications and in 2 cases, HAT was discovered fortuitously on duplex sonography. The role of imaging modalities is emphasized. Duplex sonography is the best non-invasive screening method and we recommend a routine daily examination in the first 2 weeks. CT is the most useful method to assess the extension of liver infarction. PTC remains necessary to evaluate biliary complications and to plan the best therapeutic approach in this devastating event. Two patients died, 2 had to be retransplanted (one patient twice) and are doing well, 2 are on a waiting list for retransplantation and one underwent an emergency surgical arterial desobstruction and is completely asymptomatic. PMID- 2186346 TI - Ultrasound study of acute appendicitis in children with emphasis upon the diagnosis of retrocecal appendicitis. AB - Acute appendicitis in children frequently presents equivocal clinical manifestations. Delay of the proper diagnosis and unnecessary laparotomies are common. Abdominal ultrasound has proved to be useful in the diagnosis of acute appendicitis in adults. We have performed a preoperative ultrasound study in 368 children with acute appendicitis. Among the, 92 had a retrocecal appendicitis. Ultrasound established the correct diagnosis in 92.6% of patients, and in 94.5% of those with a retrocecal appendicitis. At our institution an abdominal sonography is performed on any child with a doubtful clinical diagnosis of acute appendicitis, helping the surgeon to take the decision to perform a laparotomy. PMID- 2186347 TI - Acoustic power measurements of Doppler ultrasound devices used for perinatal and infant examinations. AB - Acoustic power output levels were measured in four different pulsed Doppler systems (transcranial, Duplex mode, colour mode, miniature for continuous monitoring) currently used for examination of fetal and infant blood flow velocities. The frequencies of the transducers ranged from 2 to 8 MHz. The devices were studied at three to five different intensity settings. The measurements were performed using the radiation force balance of the Fraunhofer Institut, which was especially adapted for this study. Each of the four devices was tested while running in its commonly used mode, and comparison showed that their acoustic power values varied widely: 96.8 mW (2 MHz, EME TC2-64B), 8.7 mW (5 MHz, ATL Mk 500), 61.9 mW (3.5 MHz, Acuson 128) and 13.5 mW (5 MHz, HP 77020). All transducers had total power output levels below the limits recommended by the American Institute for Ultrasound in Medicine and Biology in the conclusions on a thermal bioeffects mechanism, which were approved in October 1987. PMID- 2186348 TI - Prenatal ultrasound diagnosis of multiple cardiac rhabdomyomas. AB - We report on a neonate with multiple cardiac rhabdomyomas, including a huge rhabdomyoma of the left ventricular posterior wall. Prenatal ultrasonography performed because of supraventricular tachycardia led to the diagnosis in the 28th week of gestation. Postnatal echocardiography confirmed the prenatal diagnosis. The tumor could not be removed surgically and the child died as a result of intractable arrhythmia at the age of 5 days. The diagnosis of multiple cardiac rhabdomyomas was confirmed by autopsy. PMID- 2186349 TI - Hereditary pancreatitis: early ultrasound appearances. AB - The radiological findings in a family with hereditary pancreatitis (HP) are presented. The value of ultrasound in the diagnosis and in the screening of family members is illustrated, in addition to its use in following the clinical course and complications in a severely affected child. We demonstrate that pancreatic duct abnormalities, not previously described, are present prior to the appearance of the typical pancreatic calcifications of HP. PMID- 2186350 TI - Evaluation and management of febrile infants younger than 60 days of age. PMID- 2186351 TI - Evaluation of aztreonam and ampicillin vs. amikacin and ampicillin for treatment of neonatal bacterial infections. AB - In a prospective randomized, open study we evaluated aztreonam (AZ) for treatment of neonatal bacterial infections. There were 147 patients enrolled in the study; 75 received AZ and ampicillin (AMP) and 72 amikacin (AM) and AMP (conventional therapy). Twenty-eight AZ/AMP-treated patients and 32 conventionally treated patients had bacteriologically documented infections caused by gram-negative enteric bacilli or Pseudomonas species. Treatment groups were comparable in age, clinical status, and type and severity of underlying disease at the time of enrollment. Bronchopneumonia and infections caused by Pseudomonas species occurred significantly more often in AM/AMP-treated patients compared with patients given AZ/AMP. Sepsis was documented in 83% of patients in each treatment group and Gram-negative enteric bacilli and Pseudomonas species were the principal pathogens. Median peak serum bactericidal titers against the etiologic agent were 1:64 for the AZ/AMP and 1:16 for AM/AMP-treated patients. Case fatality rates resulting from the primary infection were 7 and 22% (P = 0.011), superinfection occurred in 39% and 34% and treatment failure occurred in 7 and 28% (P = 0.036) of the AZ/AMP and AM/AMP-treated patients, respectively. No clinical adverse reactions were observed in either group. Based on these results aztreonam appears to be at least as effective as and possibly more effective than amikacin when used initially with ampicillin for empiric treatment of neonatal bacterial infections. PMID- 2186353 TI - Rat tapeworm (Hymenolepis diminuta) infection in a child. PMID- 2186352 TI - Psoas abscess in children. PMID- 2186354 TI - Group A streptococcal proctitis and balanitis. PMID- 2186355 TI - Group B streptococcal colonization in Medellin, Colombia. PMID- 2186356 TI - Acute transverse myelitis in a 6-year-old girl with schistosomiasis. PMID- 2186357 TI - Rapid antigen testing for streptococcal pyoderma in private practice. PMID- 2186358 TI - Our forgotten genius: W G Horner. PMID- 2186359 TI - Influence of pulsatile perfusion upon renin release from the isolated perfused rat kidney. AB - It is well established that renin release from the juxtaglomerular epithelioid cells in the media of the afferent arteriole strongly depends on the mean renal perfusion pressure, whereas a possible influence of the pulsation of blood pressure on renin release has only occasionally been investigated, and the results are contradictory. Such an influence on renin release cannot be excluded because pulsation is known to modulate arterial baroreceptors and vascular tone in some resistance vessels. In the isolated perfused rat kidney, we found a pulsation amplitude-dependent inhibition of renin release that could be blocked either by vasodilatation or by calcium channel blockade. The inhibition occurred at perfusion pressures between 85 and 125 mm Hg. The underlying pulsation pressure-sensitive mechanism has to be ascribed integrating properties, because a constant-flow pressure rise to the "systolic" value of pulsatile perfusion resulted in virtually the same inhibition of renin release. Moreover, a reduced urine flow during pulsatile perfusion provides evidence for preglomerular constriction under these conditions. It is concluded that, besides pathological changes of renal perfusion pressure, variations of the pulse amplitudes, e.g. resulting from renal artery stenosis or atherosclerosis, may also influence renin release and contribute to renovascular hypertension. PMID- 2186360 TI - Stimulation of renin synthesis in the hydronephrotic kidney during sodium depletion. PMID- 2186361 TI - DNA recombination during PCR. AB - PCR co-amplification of two distinct HIV1 tat gene sequences lead to the formation of recombinant DNA molecules. The frequency of such recombinants, up to 5.4% of all amplified molecules, could be decreased 2.7 fold by a 6 fold increase in Taq DNA polymerase elongation time. Crossover sites mapped essentially to three discrete regions suggesting specific Taq DNA polymerase pause or termination sites. PCR mediated recombination may be a problem when studying heterogeneous genetic material such as RNA viruses, multigene families, or repetitive sequences. This phenomenon can be exploited to create chimeric molecules from related sequences. PMID- 2186362 TI - Activation of the Klebsiella pneumoniae nifU promoter: identification of multiple and overlapping upstream NifA binding sites. AB - The Klebsiella pneumoniae nifU promoter is positively controlled by the NifA protein and requires a form of RNA polymerase holoenzyme containing the rpoN encoded sigma factor, sigma 54. Occupancy of the K. pneumoniae nifU promoter by NifA was examined using in vivo dimethyl sulphate footprinting. Three binding sites for NifA (Upstream Activator Sequences, UASs 1, 2 and 3) located at -125, 116 and -72 were identified which conform to the UAS consensus sequence TGT-N10 ACA. An additional NifA binding site was identified at position -90. The UASs located at -125 (UAS1) and -116 (UAS2) overlap and do not appear to bind NifA as independent sites. They may represent a NifA binding site interacting with two NifA dimers. UAS3 is located at -72, and abuts a binding site for integration host factor (IHF) and is not normally highly occupied by NifA. In the absence of IHF UAS3 showed increased occupancy by NifA. Mutational and footprinting analysis of the three UASs indicates (1) IHF and NifA can compete for binding and that this competition influences the level of expression from the nifU promoter (2) that UAS2 is a principle sequence of the UAS 1,2 region required for activation and (3) that none of the NifA binding sites interacts with NifA independently. In vivo KMnO4 footprinting demonstrated that NifA catalyses open complex formation at the nifU promoter. IHF was required for maximal expression from the nifU and nifH promoters in Escherichia coli, and for the establishment of a Nif+ phenotype in E. coli from the nif plasmid pRD1. PMID- 2186363 TI - The initiation of translation in E. coli: apparent base pairing between the 16srRNA and downstream sequences of the mRNA. AB - Bacteriophage T7's gene 0.3, coding for an antirestriction protein, possesses one of the strongest translation initiation regions (TIR) in E. coli. It was isolated on DNA fragments of differing length and cloned upstream of the mouse dihydrofolate reductase gene in an expression vector to control the translation of this gene's sequence. The TIR's efficiency was highly dependent on nucleotides +15 to +26 downstream of the gene's AUG. This sequence is complementary to nucleotides 1471-1482 of the 16srRNA. Similar sequences complementary to this rRNA region are present in other efficient TIRs of the E. coli genome and those of its bacteriophages. There seems to be a correlation between this sequence homology and the efficiency of the initiation signals. We propose that this region specifies a stimulatory interaction between the mRNA and 16srRNA besides the Shine-Dalgarno interaction during the translation initiation step. PMID- 2186364 TI - Programmed ribosomal frameshifting generates the Escherichia coli DNA polymerase III gamma subunit from within the tau subunit reading frame. AB - The Escherichia coli dnaX gene encodes both the tau and gamma subunits of DNA polymerase III holoenzyme in one reading frame. The 71.1 kDa tau and the shorter gamma share N-terminal sequences. Mutagenesis of a potential ribosomal frameshift signal located at codons 428-430 without changing the amino acid sequence of the tau product, eliminated detectable synthesis of the gamma subunit, suggesting that the reading frame is shifted at that sequence and gamma is terminated by a nonsense codon located in the -1 frame 3 nucleotides downstream of the signal. This seems to be the first known case of a frameshift which is used, along with the termination codon in the -1 frame, to terminate a peptide within a reading frame. [Mutagenesis of a dibasic peptide (lys-lys) at codons 498-499, the site at which a tau'-'LacZ fusion protein was cleaved in vitro (1) had no effect on gamma formation in vivo, suggesting that cleavage observed in vitro is not the mechanism of gamma formation in vivo. PMID- 2186365 TI - A relational database of transcription factors. AB - Recent advances in the understanding of eukaryotic gene regulation have produced an extensive body of transcriptionally-related sequence information in the biological literature, and have created a need for computing structures that organize and manage this information. The 'relational model' represents an approach that is finding increasing application in the design of biological databases. This report describes the compilation of information regarding eukaryotic transcription factors, the organization of this information into five tables, the computational applications of the resultant relational database that are of theoretical as well as experimental interest, and possible avenues of further development. PMID- 2186366 TI - 2-(p-Nitrophenyl)-2'-deoxyadenosine, a new type of mutagenic nucleoside. AB - A crude preparation of 2-phenyladenosine was found to be mutagenic in the Ames Salmonella assay. In the purification of this preparation, it was revealed that 2 phenyladenosine itself was nonmutagenic but that 2-(m- and p-nitrophenyl) adenosines (5m,p) contaminating the sample were the mutagenic principles. A structure-activity relationship study was carried out, and it was found that 5p, 2-(p-nitrophenyl)-adenine (7p), and 2-(p-nitrophenyl)-2'-deoxyadenosine (15p) were strongly mutagenic toward S. typhimurium TA98 and TA100 without metabolic activation, the potency being in the order 15p greater than 7p greater than 5p. The potency of 15p in TA98 was one order of magnitude greater than that of 4 nitroquinoline N-oxide. 15p also showed mutagenicity in the mouse cell line FM3A in culture. PMID- 2186367 TI - Efficient trans-activation by the HIV-2 Tat protein requires a duplicated TAR RNA structure. AB - Human immunodeficiency viruses HIV-1 and HIV-2 encode a Tat protein that activates transcription from the long terminal repeats. The target for transactivation is termed the trans-acting responsive (TAR) element. TAR has an extensively folded RNA secondary structure and is present at the 5' end of all viral mRNAs. Considerable similarities exist between both Tat and TAR of the two viruses. The TAR element of HIV-2 (TAR-2) resembles a tandem duplication of the TAR-1 hairpin structure. Tat-2 conserves many of the protein domains in Tat-1, although it is slightly larger than its counterpart. Given the similarity between the two Tat proteins, it is somewhat unexpected that HIV-2 Tat (Tat-2) only poorly activates the heterologous TAR-1 element. Here, we tested whether the duplicated structure of TAR-2 is required for full Tat-2 activity. We show that the addition of a second TAR hairpin to TAR-1 increased its Tat-2 responsiveness by 3-fold. PMID- 2186368 TI - Application of a new method of pattern recognition in DNA sequence analysis: a study of E. coli promoters. AB - An algorithm from the pattern recognition theory 'generalized portrait' was used to find a distinguishing vector (scoring matrix) for E. coli promoters. We have attempted to solve three closely linked problems: (i) the selection of significant features of the signal; (ii) subsequent multiple alignment and (iii) calculation of the vector coordinates. Promoters with known strength have been successfully ranked in the correct order using this vector. We demonstrate the use of this method in predicting the location of promoters. A revised consensus promoter sequence is also presented. PMID- 2186369 TI - The nucleotide sequence of ptsH gene from Klebsiella pneumoniae. PMID- 2186370 TI - Bacteriophage T4 gene 26. PMID- 2186371 TI - PCR-induced (ligase-free) subcloning: a rapid reliable method to subclone polymerase chain reaction (PCR) products. PMID- 2186372 TI - A 3.5 genome equivalent multi access YAC library: construction, characterisation, screening and storage. AB - The construction of a yeast artificial chromosome (YAC) primary gridded library of 35,000 clones from human lymphoblastoid (48,XXXX) cell line DNA is described. The average YAC size is approximately 350kb representing a greater than 3.5 times coverage of the genome. The library is stored at -70 degrees C as gridded clones on nylon filters impregnated with 20% glycerol and as glycerol suspensions of individual clones in microtitre plates providing a prolonged multi-user potential. To date we have used 14 single copy probes to screen this library by colony hybridisation as well as PCR and have isolated between 1 and 5 YAC clones for every probe. PMID- 2186373 TI - Identification of trans-dominant HIV-1 rev protein mutants by direct transfer of bacterially produced proteins into human cells. AB - A synthetic rev gene containing substitutions which introduced unique restriction sites but did not alter the deduced amino acid sequence was used as a vehicle to construct mutations in rev. Insertion or substitution mutations within a domain of Rev resulted in proteins able to inhibit the function of Rev protein in trans. Rev function was monitored in a cell line, HLfB, which contained a rev- mutant provirus. HLfB cells require the presence of rev for virus production, which was conveniently monitored by immunoblot detection of p24gag. Trans-dominant mutants were identified after expression in bacteria and delivery into HLfB cells by protoplast fusion. In addition, the trans-dominant phenotype was verified by expression of the mutant proteins in HLfB cells after cotransfection. These studies define a region between amino acid residues 81 and 88 of rev, in which different mutations result in proteins capable of inhibiting Rev function. PMID- 2186374 TI - DNA repair in a small yeast plasmid folded into chromatin. AB - The question of whether excision repair of yeast plasmids accurately reflects the repair of yeast genomic chromatin has yielded conflicting answers. These conflicts could have arisen from differences in the conformation of plasmid molecules used during these studies. We have examined excision repair of UV photoproducts in a small (2619 bp) autonomously replicating plasmid (YRp-TRURAP), known to be folded into chromatin with positioned nucleosomes in vivo, in the yeast Saccharomyces cerevisiae. A quantitative assay was used to measure the yield of cyclobutane pyrimidine dimers (PD) in plasmid DNA by measuring the fraction of Form I molecules resistant to T4 endonuclease V. After a UV dose of 100 J/m2, which yields 1.2 PD/plasmid in irradiated cells, radiation insensitive (wt) cells repair approximately 70% of the PD in TRURAP chromatin in 2 hr (a rate comparable to that of genomic chromatin). On the other hand, no measurable repair occurs in TRURAP chromatin in radiation sensitive cells (rad1) during the same time period. Thus, this small plasmid contains sufficient chromatin structure in vivo to reflect the incompetent repair of genomic chromatin seen in a rad mutant, while maintaining the competent repair level in wt cells. PMID- 2186376 TI - A family of positive regulators related to the Pseudomonas putida TOL plasmid XylS and the Escherichia coli AraC activators. AB - The XylS family consists of a least 8 different transcriptional regulators. Six of these proteins are positive regulators for the catabolism of carbon sources (benzoate and sugars) in Escherichia coli, Pseudomonas putida and Erwinia carotovora, and two of them are involved in pathogenesis in Escherichia coli and Yersinia enterocolitica. Based on protein alignments, the members of this family exhibit a long stretch of homology at the C-terminal end. The regulators involved in the catabolism of carbon sources stimulate transcription from their respectively regulated promoters only in the presence of effectors. In two of the regulators, mutations at the non-homologous N-terminus alter affinity and specificity for effectors while mutations at the conserved C-terminus part decrease activation of transcription from their corresponding regulated promoters. It is thus probable that the variable N-terminus end in this family of regulators contains the motif involved in effector recognition, while the C terminal end is involved in DNA-binding. These proteins seem to be related by common ancestry and may act through similar mechanisms of positive regulation effected through similar folding patterns. PMID- 2186375 TI - The signal for the termination of protein synthesis in procaryotes. AB - The sequences around the stop codons of 862 Escherichia coli genes have been analysed to identify any additional features which contribute to the signal for the termination of protein synthesis. Highly significant deviations from the expected nucleotide distribution were observed, both before and after the stop codon. Immediately prior to UAA stop codons in E. coli there is a preference for codons of the form NAR (any base, adenine, purine), and in particular those that code for glutamine or the basic amino acids. In contrast, codons for threonine or branched nonpolar amino acids were under-represented. Uridine was over represented in the nucleotide position immediately following all three stop codons, whereas adenine and cytosine were under-represented. This pattern is accentuated in highly expressed genes, but is not as marked in either lowly expressed genes or those that terminate in UAG, the codon specifically recognised by polypeptide chain release factor-1. These observations suggest that for the efficient termination of protein synthesis in E. coli, the 'stop signal' may be a tetranucleotide, rather than simply a tri-nucleotide codon, and that polypeptide chain release factor-2 recognises this extended signal. The sequence following stop codons was analysed in genes from several other procaryotes and bacteriophages. Salmonella typhimurium, Bacillus subtilis, bacteriophages and the methanogenic archaebacteria showed a similar bias to E. coli. PMID- 2186377 TI - Mutation frequency and spectrum resulting from a single abasic site in a single stranded vector. AB - We have investigated the mutagenic properties of an abasic site in DNA by transfecting SOS-induced and uninduced cells of E. coli with a single-stranded M13mp7-based vector that carries a single example of this lesion at one or other of two unique and adjacent sites. Random samples of progeny phage were sequenced to determine the nature of the replication events that occurred at and around these locations. 5% to 7% of the vectors could be replicated in SOS-induced cells, but only 0.1% to 0.7% of them gave plaques in the absence of SOS induction. In SOS-induced cells, 93% and 96% of the phage replicated resulted from the insertion of a nucleotide opposite the abasic site, while the remainder resulted from a targeted omission of a single nucleotide. At one of the sites, nucleotide insertions were 54% dAMP, 25% dTMP, 20% dGMP and 1% dCMP. At the other site they were 80% dAMP, 4% dTMP, 15% dGMP and 1% dCMP. The sequence variation in all but two of the 204 sequences analyzed was restricted to the abasic site itself. In the remaining two, a change at the abasic site was accompanied by a mutation at an immediately flanking nucleotide. PMID- 2186378 TI - Nucleotide sequence of the PHO81 gene involved in the regulation of the repressible acid phosphatase gene in Saccharomyces cerevisiae. PMID- 2186379 TI - ERS1 a seven transmembrane domain protein from Saccharomyces cerevisiae. PMID- 2186380 TI - Electrotransfer: direct transfer of bacterial plasmid DNA by electroporation. PMID- 2186381 TI - Yeast artificial chromosomes: rapid extraction for high resolution analysis. PMID- 2186382 TI - Tumor markers and screening tools in cancer detection. AB - The ideal cancer screening tool would be one that is sufficiently sensitive to detect early malignancy, specific to only cancer and not a host of other conditions, specific for the type of cancer, specific for the location of the cancer, commensurate to the tumor bulk, cost-effective, easy to use, safe, acceptable to the general population, and acceptable to the medical community. No one laboratory test or radiograph meets all of the preceding criteria. Great strides have been made, however, in the early diagnosis of cancer. For example, breast cancer is being diagnosed at much earlier stages because of mammography. Just a few years ago, safety was a major issue because of the high level of radiation exposure connected with mammography. Today, radiation exposure is minimal, and the benefits far outweigh the potential harm. Research must continue to perfect the existing screening tools and develop new tools that will enable the early detection of malignant disease. PMID- 2186383 TI - Biotherapy: recent advances and nursing implications. AB - Nurses have and will continue to play a crucial role in the development and application of new BRM agents and products. Joint ventures between the National Cancer Institute, traditional academic centers, and private industry have produced new partnerships expanding the number and types of biologic research studies being conducted in various patient care settings. Nursing's contributions in these new ventures are significant and ongoing. If not directly involved in studying and administering BRM agents, the nurse will be involved in the education and counseling of persons who may participate in this new cancer treatment modality. Nurses will need to be familiar with BRM because many people will query them about this new field. Dr. Ehrlich concluded his address in 1900 by stating: "We no longer find ourselves lost on a boundless sea, but that we have already caught a distinct glimpse of the land which we hope, nay, which we expect, will yield rich treasures for biology and therapeutics." Are we there yet? PMID- 2186384 TI - Radiation therapy. Recent advances and nursing implications. AB - Radiation therapy is one of the oldest treatments available for cancer management. Since the discovery of x-rays and radioactivity in the 1890s, patients have been treated with radiation. Advances in equipment and in the understanding of radiobiology permit delivery of effective doses of radiation to tumors while minimizing normal tissue damage. Recent advances in radiation have expanded the scope of treatment. Large-field, large-dose radiation, such as half body treatment, permits treatment of metastatic disease in an effective and well tolerated manner in patients too ill to travel for therapy. Total skin electron therapy has been successful in managing extensive skin disease. Hyperfractionated treatment is an experimental approach that attempts to achieve better tumor control by treating with two fractions per day. Intraoperative radiation is a conceptually sound but logistically cumbersome plan in which treatment is given in a single fraction at the time of surgery. Its full potential may be realized when the technical difficulties of administration can be overcome. Brachytherapy is the use of radioactive sources implanted directly into the tumor or in a cavity in proximity to the tumor. Techniques have improved in both surgery and radiation, which allow previously inaccessible sites such as the brain to be implanted. Early-stage breast cancer has been effectively managed with lumpectomy followed by radiation. Hyperthermia is the use of heat in conjunction with radiation. Heat has been found to enhance the effect of radiation and limit the repair of radiation damage. The properties of heat cause it to be more damaging to tumor cells than to normal ones. The ability to sensitize cancer cells to radiation and protect normal cells from radiation has been an ongoing research objective. Clinical trials are in progress to isolate effective, easily administered, and nontoxic compounds. The nurse caring for the patient receiving radiation must have an understanding of how radiation works and what the treatment goals are for the patient. Radiation is a difficult modality for patients to understand. Many fears and concerns are based on this lack of comprehension. The nurse must be prepared to describe the experience of receiving radiation and assist patients to anticipate and manage side effects. Patients need to know what to expect from therapy in terms they can understand. Recent advances and experimental treatments should be explained in terms of what is known including the rationale for the procedures.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2186385 TI - Cancer pain management. State-of-the-art nursing care. AB - Cancer pain management is a dynamic field. Advances in basic science research have tremendous implications for the clinical management of cancer pain. New drugs and innovative methods of delivering old drugs have been developed. The challenge facing clinicians is to use the newer techniques systematically and appropriately once they have been adequately tested. Nurses play a particularly important role in helping patients with cancer pain to manage their pain experience in ways that are effective for the patients to meet their personal goals. PMID- 2186386 TI - Advances in breast cancer. Implications for nursing care. AB - The role of the nurse in the care of patients with breast cancer is changing because of the many options available for medical management of the disease. Breast cancer is a treatable disease. Patients survive many years. Throughout the treatment process, patients and families may be faced with numerous decisions involving initial treatment and adjuvant therapy as well as the treatment of metastatic disease. Involvement of the patient and caregiver are crucial in this process, and they must be assisted and supported by nurses who are knowledgeable about the options and the rationale behind each of the treatment options. If this disease continues to occur in 1 out of 10 women, most nurses will be involved with some aspect of the disease either personally or professionally. PMID- 2186387 TI - Recent advances in chemotherapy. Administration and nursing implications. AB - This article provides an overview of the recent advances in the use of chemotherapy as a treatment modality with selected types of cancers. During the next decade, additional gains should be made in the development of effective therapeutic regimens with the development of new drugs and different combinations as well as changes in dosages and scheduling. It is hoped that these advances will result in prolonging disease-free as well as overall survival. Nurses caring for patients receiving these innovative and complex regimens in various care settings will be challenged to be knowledgeable, skilled, sensitive, and creative in the development of interventions to meet the unique needs of patients and their families. PMID- 2186388 TI - Advances in nursing management of patients with lung cancer. AB - Cancer of the lung is a medical and nursing challenge. Conventional treatment of lung cancer has resulted in such limited success that other treatment modalities are being investigated. Newer strategies and experimental studies have impacted on the nursing care required of these patients. Advances in oncology nursing are evident in the successful outpatient care of lung cancer patients receiving treatment, the preparation of patients for and the management of problems related to new treatment regimens, and the expansion of acute oncology nursing care for the home-bound patient. PMID- 2186389 TI - Bone marrow transplant. Recent advances and nursing implications. AB - The myriad therapies used during bone marrow transplantation are in constant flux. Major problems still need to be solved including relapse after transplant and graft rejection. More effective and less toxic conditioning regimens, acceleration of hematopoietic and immune reconstruction, and improved control of GVHD and infections are currently being studied. Nurses are vital in orchestrating the complicated care these therapies mandate as well as providing emotional support to patients and their families. Nursing research is being conducted in many areas of marrow transplantation. Quality-of-life and survivor issues have been identified as priorities by many nurses working in this field. Nurses will continue to play a pivotal role in caring for patients as marrow transplantation continues to evolve as a major form of cancer treatment. PMID- 2186390 TI - Late effects of chemotherapy. Implications for patient management and rehabilitation. AB - This article provides an overview of the late effects of chemotherapy on cardiac, gonadal, neurologic, pulmonary, and renal functions. In addition, it discusses the development of second malignancy following treatment for Hodgkin's disease, breast cancer, and childhood malignancies. As nurses caring for the cancer survivor, we must be knowledgeable about cancer chemotherapeutic agents and the potential or actual impact on cancer patients' lives. We must be creative in our approach to address the needs of the survivor and to study the long-term effects on the survivor. PMID- 2186391 TI - Recent advances in childhood cancer. AB - Major advances during the past 25 years in the treatment of childhood cancer have resulted in a dramatic improvement in disease-free survival for more than 60% of diagnosed patients. Advances in both laboratory and clinical research have demanded a concomitant expansion of nursing skill and practice to keep pace in this area. This article strives to provide an overview of recent advances in pediatric oncology in both the scientific and clinical arenas and to highlight some of the contributions made by pediatric oncology nurses. PMID- 2186393 TI - Advances in the management of nausea and vomiting. AB - The successful management of cancer-related nausea and vomiting is dependent upon many factors. An understanding of the various pharmacologic and nonpharmacologic interventions serve as the foundation for symptom control. The most important variable, however, is the nurse's commitment to alleviate these symptoms. Such commitment requires flexibility, tenacity, and a willingness to serve as a patient advocate. Regardless of the care setting, the nurse remains in a pivotal position to facilitate the optimal management of symptoms. Tremendous opportunities exist for nurses to collaborate across a variety of settings in order to ensure continuity. Such continuity enhances patient care but most important assures individuals (and their significant others) that their history is known and that they do not have to fear poor emetic control because of caregiver ignorance. The ability to initiate or support behavioral interventions demonstrates the nurse's commitment to holistic care. Such holism is the foundation and reward of cancer nursing practice. PMID- 2186392 TI - The future of oncology nursing. A historical perspective. AB - This article provides a perspective on the history of oncology nursing and the technologic and societal factors that have impacted on the development of this specialty. This article attempts to raise issues that will confront the profession of nursing as it moves into the twenty-first century. I hope that the comments and questions about the future made in this article will challenge nurses to participate in charting a preferred future for the profession of nursing in the twenty-first century. PMID- 2186394 TI - The new fat replacements. A strategy for reducing fat consumption. AB - Recent public health reports have implicated dietary fat as a major cause of chronic disease. Physicians are being called on to help their patients reduce fat consumption by guiding them toward a low-fat diet. However, high-fat foods are an important component of the American diet, and preferences for them are remarkably resistant to change. The standard strategy of suggesting to patients that they eat fewer high-fat foods and more grains, vegetables, and fruits has not, in my experience, been very effective. Fat-replacement products offer a useful new strategy for reducing fat consumption by the American public. PMID- 2186395 TI - Lyme disease. Recognizing its many manifestations. AB - Lyme borreliosis is a relatively new disease, so much remains to be learned about it. In this article, typical manifestations at each stage are reviewed. However, as the authors emphasize, diagnosis is still a challenge because a given patient may have from a few to all of the features discussed, stages often overlap, and characteristics come and go and may mimic other illnesses. PMID- 2186396 TI - Serologic testing for Lyme disease. AB - Serologic testing for antibodies is, at present, the only practical means of diagnosing Borrelia burgdorferi infection. However, specific IgM spirochetal antibodies may not be at detectable concentrations in the early stage of Lyme disease (within 6 weeks of onset). Western blot analysis may be used to confirm indirect fluorescent antibody staining or enzyme-linked immunosorbent assay results, but it is laborious and expensive. False-positive reactions caused by cross-reactivity do occur. In patients who have had subclinical Lyme disease and contract another illness that causes similar symptoms, interpretation of serologic test results may be confused by residual antibodies. Therefore, assay results should always be interpreted in conjunction with clinical and epidemiologic findings. PMID- 2186397 TI - Treatment of Lyme disease. Best use of antibiotics. AB - Lyme disease is a tick-borne illness caused by the spirochetal bacterium Borrelia burgdorferi. Recognition of the clinical manifestations and geographic range of this illness has expanded rapidly in recent years. Although much remains to be explained about this infection, most patients can be treated effectively on the basis of the clinical experience gathered to date. Antibiotics are the mainstay of therapy for all stages of illness. Development of a vaccine and improvement in laboratory diagnostic techniques glimmer on the horizon but will not replace careful clinical observation and follow-up as the foundations of management. PMID- 2186399 TI - Liposuction. What it will and won't do. AB - Liposuction is used most often to contour the body. Usually, it is done on an outpatient basis under general or regional anesthesia. Results are better in patients who have good skin turgor and are at or near their ideal weight. The recovery period is short and relatively pain-free. While there have been serious complications in a few cases, the procedure is safe when done by experienced physicians who are careful in selecting patients and cautious about the magnitude of the procedure they perform. Patient satisfaction is high, particularly when patients are selected carefully and are well-informed concerning the expected outcome. PMID- 2186398 TI - Screening for lung cancer. Is it worthwhile? AB - Prevention of lung cancer remains the best method of decreasing lung cancer mortality. Patients who smoke should be urged to quit, and children, teenagers, and young adults must not begin smoking. At high risk are smokers, especially those under 40 years of age who may have smoked two to four packs of cigarettes per day for 20 years; persons who have had a previous lung cancer; patients with bullous emphysema; patients with asbestosis; and patients with evidence of chronic airflow obstruction. Although radiographic screening may detect lung cancer earlier and lead to increased 5-year survival rates, it does not reduce lung cancer mortality rates. PMID- 2186400 TI - Is electroconvulsive therapy safe? AB - Electroconvulsive therapy is controversial and readily arouses the passions of both its supporters and detractors. In this article, Dr Schoen, an internist, discusses various aspects of this 50-year-old technique, including risks, contraindications, and physiologic effects. PMID- 2186401 TI - The Heimlich maneuver. Best technique for saving any choking victim's life. AB - The American Red Cross (ARC) and the American Heart Association (AHA) advocated backslaps, chest thrusts, and abdominal thrusts for 10 years after the Heimlich maneuver was introduced in 1974. Even after the Surgeon General in 1985 declared these methods to be "hazardous, even lethal," the ARC and the AHA continue to recommend backslaps and chest thrusts for infants under 1 year of age. ARC and AHA instructional materials that advocate use of these methods have not been recalled, and the public has not been warned of the dangers. One cause of the confusion about backslaps is the flawed belief that gas pressure alone removes a foreign body. In addition, there is lack of understanding that, compared with the Heimlich maneuver, the backslap produces an insignificant amount of the energy required to expel an object from the airway. In fact, the energy produced by the backslap drives the foreign object in the wrong direction, toward the lungs, while the energy produced by the Heimlich maneuver drives the object away from the lungs, toward the mouth. Backslaps and chest thrusts should be publicly recalled as a treatment for choking infants before further deaths and injuries occur. The Heimlich maneuver is the best rescue technique for treating choking victims of all ages. PMID- 2186402 TI - Should I trust office pregnancy tests? AB - Pregnancy tests have become quite reliable since the introduction of monoclonal antibody procedures. Even home kits use this technology and are greatly improved over earlier versions. However, as Dr Bluestein explains, use of these tests must be accompanied by an understanding of factors that can cause false results. He describes these factors and points out the need for further testing and obstetric consultation in some situations. PMID- 2186403 TI - [Phthisiology as a medical and scientific specialty]. PMID- 2186404 TI - [Problems of respiratory diseases in adolescents]. PMID- 2186405 TI - Chitin metabolism: a target for drugs against parasites. AB - Chitin is an important component of the exoskeleton of arthropods and of the egg shell in nematodes, but it does not occur in vertebrates. Therefore, it represents a useful target for drugs against ectoparasitic crustaceans, insects and endoparasitic nematodes. In this review we describe the basic characteristics of chitin, chitin synthesis and degradation and the hormonal regulation of chitin metabolism. Substances interfering with chitin metabolism like benzoylphenyl-urea derivatives but also some recently detected compounds are described. The necessity for a more detailed understanding of chitin metabolism and the establishment of better model systems, like e.g. chitin producing insect cell lines, is stressed and some examples are given in this review. PMID- 2186406 TI - Biochemical evidence of the antigenic cell surface heterogeneity of Leishmania mexicana. AB - In the present study, an enzymatical and structural analysis of Leishmania mexicana cell-surface components was carried out, demonstrating that protease and acid phosphatase activities were present at the L. mexicana cell surface. These findings correlate with the expression of the main components detected on the surface of L. mexicana promastigotes: the 50-kDa component is responsible for the acid phosphatase activity, whereas glycoprotein 65 (gp65) was characterized as the structural polypeptide of the surface protease. Furthermore, the 50- and 65 kDa antigens were found to be structurally different, inasmuch as no homology was observed in their peptide digestion profiles. The results presented in this communication confirm heterogeneity in the expression of the surface components of L. mexicana promastigotes at both the structural and the biochemical level. PMID- 2186407 TI - Development and interactions of Trypanosoma rangeli in and with the reduviid bug Rhodnius prolixus. AB - Two strains of Trypanosoma rangeli and three strains of Rhodnius prolixus were used in various combinations to transmit the trypanosomes via the reduviid bug. A persisting infection in the midgut lumen posterior to the stomach resulted in all 2,500 bugs being third and fourth instars. Infectious, metacyclic forms developed exclusively in the salivary glands; forms excreted with bug feces were noninfectious to mice. The midgut epithelium was the main barrier to transmission of the parasite. In only 2%-5% of the infected bugs was it penetrated, and no correlation with any parameter tested could be found. The trypanosomes passed through the gut epithelium by an intracellular route; they were contained in a parasitophorous vacuole. The salivary glands of R. prolixus were found to be infected whenever the hemolymph was infected, after a successful penetration of the gut epithelium, or after injection of T. rangeli. On the other hand, hemolymph infections in Triatoma infestans were eliminated within a few days, and the salivary glands of this bug were never invaded. Pathogenic effects of T. rangeli on R. prolixus could be seen in midgut epithelial cells by a loss of cytoplasm and in muscle and salivary gland cells by very high parasite densities. However, as the penetration rate of the gut is low, T. rangeli is not likely to prove to be efficient in natural control of R. prolixus. PMID- 2186408 TI - Growth of a Japanese isolate of Taenia crassiceps in intermediate and definitive hosts. AB - Higher infection rates were observed in gerbils and voles than in ICR mice after oral inoculation with eggs of a Japanese isolate of Taenia crassiceps. Asexual reproduction of T. crassiceps cysticerci was observed in all gerbils and voles infected i.p. with the cysticerci. However, ICR mice and Wistar rats were not suitable for the asexual proliferation of T. crassiceps. The hooks of cysticerci from mice were smaller than those from gerbils. In experimentally infected puppies, parasite development was noted as follows: strobilation and initial differentiation of the genital primordia on day 7 postinoculation (p.i.), appearance of the testes on day 9, observation of the ovaries on day 10, and development of the lateral branches of the uterus on day 15. The prepatent period was 27-31 days. After day 15 p.i., most of the worms were recovered from the middle third of the small intestine. The number of proglottids shed per day by each strobila was about 1. The number of eggs contained in a gravid segment was about 13,000. PMID- 2186409 TI - Reduced levels of PGE2 uptake by intact reno-medullary collecting tubule cells isolated from the spontaneously hypertensive rat and the identification of an intracellular PGE2 receptor/binding protein. AB - Prostaglandin E2 (PGE2) is thought to be involved in the control of NaCl loading in the kidney. Since the ability to balance salt concentrations across the nephron appears to be impaired in the Spontaneously Hypertensive Rat (SHR), the uptakes of PGE by isolated medullary collecting tubule cells (MCT) from both SH and normotensive (NT) rats were compared. A rabbit antiserum directed against PGE2 revealed by flow cytometry the active internalisation of exogenous ligand by a high density fraction of intact MCT cells from NT tissue. Conversely, PGE2 uptake by the same fraction was markedly reduced. The monoclonal antibodies (MoAbs) W2.44 and SH6.6 raised against a 45,000 X g fraction of medullary tissue and which blocked binding of the anti-PGE2 serum, identified by Western blotting, an intracellular PGE2 receptor or binding protein (PGER) of 16 k daltons. No alteration in the structure or level of expression of this antigen could be detected in the MCT fractions isolated from the SHR. It is suggested that an impairment of PGE2 membrane transport in the renal medulla may be a contributory factor to the SH condition. PMID- 2186410 TI - Problems in the search for cognition enhancers. AB - Drugs which enhance cognition may benefit the two largest groups of psychiatric patients who have been bypassed during the psychopharmacological revolution of the past 35 years: those with development mental disabilities and those with brains ravaged by senile dementias. But who among us would not benefit from such a drug, if indeed it could enhance normal performance? Establishing suitable animal models for developing such drugs has been a major problem. Lesioning experiments dictate the answers as well as the questions, delimiting the type of drug to remedy the defect. Other lesions which are less specific, such as anoxia or deficiency of some vitamin or metabolite, may not have particular relevance to the clinical situation. The best animal models would employ learning paradigms that mimic the problems encountered by the disabled patient. Testing new compounds in the clinic also has problems. Subjects should not be so deteriorated to require a miracle drug to show any effect. The characteristic variability in function of such patients must be taken into account, to assure that any changes are not simply within the normal range of variability. Thus, we may need a new kind of statistical approach to analyzing data, based more on individual responses than on group means. Finally, the end-points should be based on an improved quality of life both for patients and their caretakers. We need a different set of measurement criteria. Despite these difficulties the search for drugs which enhance cognition should not be delayed. The payoffs of success will be high for everyone. PMID- 2186411 TI - Early human trials in the assessment of cognition activators. AB - The assessment of cognition enhancers in the clinic is a broad topic that can be addressed from both academic/theoretical and therapeutic/drug development perspectives. The most important first step is to decide which perspective one is employing and to clearly specify, a priori, the goal of any intended study. Since the therapeutic benefit of cognition enhancers is not apparent until after many weeks of exposure, it is virtually impossible to demonstrate efficacy in early, short-duration Phase 2 trials. It is possible, however, to gain some knowledge of the doses that effect CNS, rCBF, PET etc. in either normal volunteers or the population of interest. However, these results should not be interpreted as evidence for, or lack of, efficacy. Recently, there has been growing interest in the reversal of scopolamine- or benzodiazepine-induced memory deficits in humans. A major problem is the potential for overinterpretation of the results of such studies. From a drug development approach, it is necessary to utilize larger numbers of subjects and longer-term studies. Specification of the indication should be as precise as possible and the outcome measures should accurately reflect both the current state of the patient and the course of the disease. The absence of normative and longitudinal data on such measures is a hurdle that is only now being overcome. Such data provide a scientific basis for the determination of the types of design and sample sizes that give adequate power to thoroughly assess new cognition enhancers. PMID- 2186412 TI - Therapeutic target for cognition enhancers: diagnosis and clinical phenomenology. AB - Uncertainty concerning therapeutic targets has probably retarded the development of cognition-enhancing drugs. While enhancement of normal cognitive function may be a legitimate goal it is unlikely that drugs developed without a clear clinical indication will ever be approved by regulatory authorities. Normal aging as a target would also appear to be excluded. The main debate is whether drugs should be developed for specific disease states (e.g., Alzheimer's), particular syndromes (e.g., AAMI) or for treating symptoms (e.g., memory deficits). Although targeting disease states appears the least problematic, it would be difficult to include many potentially treatable patients in such studies. In this respect, the status of AAMI is still the subject of much debate. In any case, it is important that trial populations be as homogeneous as possible, with clear diagnostic criteria (e.g., defined memory impairment, Hachinski score, CT scans) and that patients be moderately to severely affected. PMID- 2186413 TI - Neurochemical substrates of human aging and dementia. AB - Further development of clinical models of dementia to augment present unsatisfactory animal models, is of central importance to the understanding of the neurochemistry of dementia. Furthermore, present definitions of the neurotoxic processes underlying dementing disorders will need to be improved. Routine clinical markers will be necessary for the development of any therapy beyond present attempts for symptomatic treatment with neurotransmitter replacement. PMID- 2186414 TI - Early clinical testing of cognition enhancers: prediction of efficacy. AB - The major problem in predicting clinical efficacy from animal experimental results and phase I data is the lack of resemblance between the models used and the clinical condition. This problem is complicated by the diversity of the potential mechanisms of action of new compounds. A further question is whether Phase I studies should be used as predictors of clinical efficacy at all. Should they be used simply for determining pharmacologically active dose ranges and tolerance? If used as predictors should drug development stop if negative results are obtained? These questions were not resolved. It was nonetheless suggested that some human models (e.g. scopolamine-induced amnesia, hypoxia-induced performance deficits) were indeed potential predictors of clinical response and, in addition, were analogous to similar models in animals. On the other hand characterisation of quantified EEG (QEEG) profiles remained controversial. PMID- 2186415 TI - Late clinical testing of cognition enhancers: demonstration of efficacy. AB - The major difference between clinical trials for efficacy and Phase I trials is their duration; clinical trials of cognition enhancers, for example in senile dementia, require at least 6 months. Because no widely accepted treatment is available, the methodology for these trials is still in a the process of refinement. Double blind placebo-controlled trials are considered to be mandatory particularly by the FDA. Parallel group designs seem preferable and the so-called "enriched design" seems to possess advantages over more classical procedures. Outcome measures should include ratings by clinicians and family members. Self reports are considered to be unreliable in Alzheimer patients but may be less problematic in AAMI. Psychometric tests of cognition and motor skill should also be included. An essential and pragmatic outcome criterion is, however, the quality of daily life. PMID- 2186416 TI - The development of behavioral tests to assess the effects of cognitive enhancers. AB - The search for drugs that enhance cognition requires the development of behavioral tests for animals. These tests must be able to identify potentially therapeutic drugs and reject ineffective drugs. A reference compound for cognitive enhancement does not exist, and may not be a reasonable goal. Therefore, a coherent conceptual and experimental framework is needed to organize the various research endeavors in this area. This paper proposes a framework to assist in the development and evaluation of specific behavioral tests. It requires explicit identification of the goals of the research, the cognitive process, the neural systems involved in the process, the selectivity and sensitivity of tasks that measure the process, the validity of the behavioral tasks as a model to predict the effects of the drug in humans. PMID- 2186417 TI - Psychopharmacological strategies in the search for cognition enhancers. AB - In order to discover and develop drugs to treat cognitive decline, animal tests are needed which will predict clinical activity. The process of developing such animal models does not differ, in principle, from the approaches used in other areas of psychotropic drug research. One research approach involves attempts to create models homologous with the disorder to be treated. This requires a thorough analysis of the clinical problem and an attempt to reproduce the biological and behavioral aspects of the disorder in animals. Recent studies of the effects of certain brain lesions on learning in monkeys or rats as models of Alzheimer's disease may go some way towards developing an animal model for this disorder. However, it is arguable whether this approach to "modelling" has ever had much success in psychopharmacology. A more pragmatic strategy involves the development of what are sometimes called emperical models, according to which any biological and behavioral test can be used if it provides a reasonable prediction of activity in the clinic. For example, the much used passive avoidance test in rodents does not need to model human cognition if it accurately predicts clinical activity. The extent to which this approach can be used successfully for evaluating cognition-enhancing drugs is discussed in view of the many drugs already marketed as cognition enhancers. PMID- 2186418 TI - Biochemical strategies in the search for cognition enhancers. AB - Memory is a complex multi-event procedure which is profoundly influenced by the overall psychological state. It is thus evident that there cannot be a "memory transmitter" and that many neurotransmitter systems are implicated in different parts of the cognitive process. In general, memory effects resulting from manipulation of the catecholamine systems are a reflection of altered arousal. Modification of cholinergic transmission or that of certain neuropeptides such as vasopressin would appear, however, to involve more directly the memory process itself. This article presents a brief overview of the part played by various neurotransmitter systems in cognitive function and suggests a number of research strategies by which new cognition enhancers may be sought. PMID- 2186419 TI - Behavioral models of memory and amnesia. AB - In modelling memory and amnesia, the different forms of cognition must be distinguished. For memory, distinctions between acquisition, storage, and retrieval must be made and the different kinds of memory (e.g., immediate, working, reference) identified. Other notions, such as attention, orientation, and vigilance also belong under the heading "cognition". Thus the term "cognition enhancer" is imprecise because it does not indicate which kind of cognition is to be enhanced. Animal models should be developed for each type of cognition, be based on information from the clinic, and attempt to be specific. Examples of models more specific than the passive avoidance test were discussed and included the radial maze, in which different kinds of memory could be analyzed and correlated with, for example, changes in central cholinergic activity. From the point of view of drug development an important distinction was made between "empirical" and "simulation" models. In other areas of psychopharmacology "empirical" models have been widely used because they show predictable responses to known reference compounds. In the field of cognition there are no generally recognized reference compounds and therefore no "empirical" models. There is therefore a need for "simulation" models which imitate the various aspects of cognition and its pathology. The major criterion for validating this kind of model is that it should show changes similar to those observed in humans either resulting from a particular pathology or from a particular drug treatment. PMID- 2186421 TI - Electrophysiological models for the study of cognition enhancers. AB - Electrophysiological approaches range from global EEG studies to single unit recordings. Quantified EEG studies indicate that cognition enhancers increase the power of fast-frequency (beta) EEG activity in humans and the duration of hippocampal theta in animals. A problem here is the distinction between improved cognition and increases in general arousal, although the two might have the same end effect. A second global approach is the use of the evoked potential or even the conditioned evoked potential, for example the P 300 wave. This approach, using defined brain circuits, would appear to be more specific than global EEG models. Both approaches can be used in parallel studies in animals and man. Studies at more cellular levels can only be used in animals and suffer from severe constraints. The most precise approach, single cell recording, cannot be conducted in freely behaving animals, whereas multi-unit approaches in awake animals tend to produce many artefacts. However, techniques using microintophoretically applied drugs in freely moving rodents and monkeys can contribute to the understanding of mechanisms of action. In vitro studies, for example long-term potentiation in hippocampal slices, may represent a neuronal model of learning but its role in normal brain function has still not been elucidated. PMID- 2186420 TI - Biochemical models for cognition enhancers. AB - Although the etiology of Alzheimer's disease includes a wide range of dysfunction, the most essential dysfunction is probably in the mesolimbic acetylcholine (ACh) system. Three novel approaches to modulating ACh function were considered, somatostatin, serotonin (5-HT) and modulation of cortical ACh tone through angiotension II. Concerning somatostatin there is no correlation between the decrease in somatostatin binding sites in brain and choline-acetyl transferase activity suggesting that modulating somatostatin is not a promising therapeutic approach to Alzheimer's disease. With 5-HT, evidence suggests that 5 HT receptors (in particular 5HT1A) are located on cholinergic projections and behavioral evidence suggests 5-HT modulation of memory function. This area could therefore develop rapidly, particularly in view of the recent discovery of numerous subtypes of 5-HT receptor. Concerning the third approach, recent evidence has shown that angiotensin converting enzyme (ACE) inhibitors can facilitate ACh release and also possess cognition enhancing activity. The possibility was also evoked that drugs such as piracetam might prevent age related decreases in ACh receptor density. Concerning trophic factors (e.g. glutamate-induced neuronal sprouting) most approaches have induced amnesia but the search for partial glutamate agonists may have potential. Finally, a neuronal transplant approach was considered but was thought to be very difficult in view of the global brain shrinkage associated with aging and Alzheimer's disease. PMID- 2186422 TI - Models of hypoxia and cerebral ischemia. AB - Most models of hypoxia and ischemia are used for evaluating the metabolic consequences of cerebral insult. They have also been used for inducing cognitive disturbance. The pathological cascade after severe hypoxia or ischemia includes decreased ATP, influx of Ca2+ and Na+ with decrease in intracellular K+ leading to depolarization, release of glutamate, noradrenaline and acetylcholine, changes in neuronal plasticity, cell death, and cognitive impairment. Possible pharmacological mechanisms for protecting brain function include blockade of Ca2+ influx, inhibition of cell swelling, regulation of membrane potential, inhibition of neurotransmitter release and inhibition of excitatory amino-acid receptors. Among the existing models, many suffer from poor reproducibility and standardization. Two models which are more satisfactory in this respect are global transient ischemia in gerbils induced by bilateral carotid occlusion and focal ischemia in rats induced by occlusion of the middle cerebral artery. Although clear protective effects have been observed in both kinds of model (e.g., with NMDA antagonists, Ca2+ antagonists, PAF antagonists) it is frequently difficult to extrapolate these effects to disorders associated with memory impairment. PMID- 2186423 TI - A cognitive model of drug urges and drug-use behavior: role of automatic and nonautomatic processes. AB - Contemporary urge models assume that urges are necessary but not sufficient for the production of drug use in ongoing addicts, are responsible for the initiation of relapse in abstinent addicts, and can be indexed across 3 classes of behavior: verbal report, overt behavior, and somatovisceral response. A review of available data does not provide strong support for these assumptions. An alternative cognitive model of drug use and drug urges is proposed that hypothesizes that drug use in the addict is controlled by automatized action schemata. Urges are conceptualized as responses supported by nonautomatic cognitive processes activated in parallel with drug-use action schemata either in support of the schema or in support of attempts to block the execution of the schema. The implications of this model for the assessment of urge responding and drug-use behavior are presented. PMID- 2186424 TI - Models of integration given multiple sources of information. AB - Several models of information integration are developed and analyzed within the context of a proto-typical pattern-recognition task. The central concerns are whether the models prescribe maximally efficient (optimal) integration and to what extent the models are psychologically valid. Evaluation, integration, and decision processes are specified for each model. Important features are whether evaluation is noisy, whether integration follows Bayes's theorem, and whether decision consists of a criterion rule or a relative goodness rule. Simulations of the models and predictions of the results by the same models are carried out to provide a measure of identifiability or the extent to which the models can be distinguished from one another. The models are also contrasted against empirical results from tasks with 2 and 4 response alternatives and with graded responses. PMID- 2186425 TI - Dimensional overlap: cognitive basis for stimulus-response compatibility--a model and taxonomy. AB - The classic problem of stimulus-response (S-R) compatibility (SRC) is addressed. A cognitive model is proposed that views the stimulus and response sets in S-R ensembles as categories with dimensions that may or may not overlap. If they do overlap, the task may be compatible or incompatible, depending on the assigned S R mapping. If they do not overlap, the task is noncompatible regardless of the assigned mapping. The overlapping dimensions may be relevant or not. The model provides a systematic account of SRC effects, a taxonomy of simple performance tasks that were hitherto thought to be unrelated, and suggestive parallels between these tasks and the experimental paradigms that have traditionally been used to study attentional, controlled, and automatic processes. PMID- 2186426 TI - Connectionist models of recognition memory: constraints imposed by learning and forgetting functions. AB - Multilayer connectionist models of memory based on the encoder model using the backpropagation learning rule are evaluated. The models are applied to standard recognition memory procedures in which items are studied sequentially and then tested for retention. Sequential learning in these models leads to 2 major problems. First, well-learned information is forgotten rapidly as new information is learned. Second, discrimination between studied items and new items either decreases or is nonmonotonic as a function of learning. To address these problems, manipulations of the network within the multilayer model and several variants of the multilayer model were examined, including a model with prelearned memory and a context model, but none solved the problems. The problems discussed provide limitations on connectionist models applied to human memory and in tasks where information to be learned is not all available during learning. PMID- 2186427 TI - [Psychotherapy in comparison: have all really earned a prize?]. AB - The aim of the project is a comprehensive analysis of psychotherapeutic outcome research from a differential perspective. All controlled psychotherapy outcome studies which have been published until 1983 (n = 897) were carefully analyzed with an especially developed assessment-manual. Special importance was laid on those features of the results that throw some light on the comparative effects and prescriptive criteria of the therapies under investigation and their preconditions in the experimental design, measurement and statistical analysis of the respective study. The procedure is described in detail. It results in a comprehensive report on the research which has been done and the results that have been found for each psychotherapy method. An example of such a report is given. PMID- 2186428 TI - The evolution of seasonal delayed implantation. AB - Seasonal delayed implantation has been described in 47 mammalian species in ten families, and has evolved independently at least 17 times. After reviewing earlier explanations for the phenomenon I present a hypothesis to explain the evolution of seasonal delay. I have assumed that females can increase their fitness by choosing their mates. Consequently, mating should take place during that time of year when the possibilities for female choice or male competition are greatest. Time of birth is determined by ecological factors promoting survival of the young, thereby setting certain constraints on the scheduling of the mating season. In certain situations, however, the possibilities for female choice or male competition can be increased by mating earlier; delay will increase female fitness, and will thereby evolve. The hypothesis has been applied to all cases of seasonal delayed implantation. PMID- 2186429 TI - Evolution in bacterial plasmids and levels of selection. AB - Gene flow between different reproductive units such as bacterial plasmids and chromosomes presents unusual problems for evolutionary analysis. Far more than in eukaryotes, reproductive advantages at several levels of selection--genes, transposons, plasmids, cells, and clones--must be considered simultaneously to understand plasmid evolution. No level consistently prevails in conflict situations, and some reproductive units carry genes that restrain their own reproduction or survival, apparently to enhance the reproduction or survival of the higher-level reproductive units that carry them. Despite gene flow between plasmids and chromosomes, genes for certain functions show strong tendencies to occur on plasmids while others consistently occur on chromosomes. Functions generally associated with plasmids are diverse, but all are useful only in locally restricted contexts; it is argued that the selective consequences of the greater horizontal (within generation) transmission of plasmids are responsible for this pattern. The tendency for prokaryote transposons, which are also horizontally mobile, to carry genes similar to those commonly on plasmids supports this argument. The apparent trends in eukaryote plasmids and transposons to lack these same characters also accords with predictions of the local adaptation hypothesis, because genes on these genetic units are generally no more horizontally mobile than chromosomal genes. There are theoretical reasons to expect that plasmid genes tend to evolve more rapidly than chromosomal genes. "The selfish interests of genes have manifestly produced 'vehicles' in the forms of organelles, cells, individuals and yet higher units. If evolution is to predict as well as describe, then selfish interests must be understood in the framework of the constraints and opportunities generated by these 'vehicles'" (Buss, 1987, p. 182). PMID- 2186430 TI - Inhibition of hematopoietic recovery from radiation-induced myelosuppression by natural killer cells. AB - We have examined the role of natural killer (NK) cells in situ in the recovery of marrow hematopoiesis in B6D2F1 mice receiving various doses of total-body irradiation (TBI) as a well-characterized model for treatment-induced myelosuppression. Applying an in situ cytotoxic approach for ablating NK 1.1 cells, we have demonstrated that NK 1.1 cells differentially inhibit the recovery of hematopoietic stem cells (CFU-S) and their progenitor cells committed to granulocyte-macrophage differentiation from a sublethal dose of TBI (9 Gy) while not affecting the recovery of progenitor cells committed to either erythroid or megakaryocyte differentiation from TBI. However, recoveries of CFU-S and progenitor cells were unaffected by the ablation of NK cells prior to a moderate dose of TBI (2 Gy). These findings provide in situ evidence that NK cells are potential inhibitors of hematopoietic recovery from treatment-induced myelosuppression. PMID- 2186431 TI - Quinolone therapy of Klebsiella pneumoniae sepsis following irradiation: comparison of pefloxacin, ciprofloxacin, and ofloxacin. AB - Exposure to whole-body irradiation is associated with fatal gram-negative sepsis. The effect of oral therapy with three quinolones, pefloxacin, ciprofloxacin, and ofloxacin, for orally acquired Klebsiella pneumoniae infection was tested in B6D2F1 mice exposed to 8.0 Gy whole-body irradiation from bilaterally positioned 60Co sources. A dose of 10(8) organisms was given orally 2 days after irradiation, and therapy was started 1 day later. Quinolones reduced colonization of the ileum with K. pneumoniae: 16 of 28 (57%) untreated mice harbored the organisms, compared to only 12 of 90 (13%) mice treated with quinolones (P less than 0.005). K. pneumoniae was isolated from the livers of 6 of 28 untreated mice, compared to only 1 of 90 treated mice (P less than 0.001). Only 5 of 20 (25%) untreated mice survived for at least 30 days compared with 17 of 20 (85%) mice treated with ofloxacin, 15 of 20 (75%) mice treated with pefloxacin, and 14 of 20 (70%) treated with ciprofloxacin (P less than 0.05). These data illustrate the efficacy of quinolones for oral therapy of orally acquired K. pneumoniae infection in irradiated hosts. PMID- 2186432 TI - Techniques in cardiac transplantation. PMID- 2186433 TI - Immunologic aspects of rejection. PMID- 2186434 TI - The role of magnesium in cardiac arrhythmias. PMID- 2186435 TI - [Biology of bone marrow transplantation--from radiation protection to life sciences]. PMID- 2186436 TI - [Measurement of radiation energy and its application (7). III. Energy measurement of alpha-rays and its applications]. PMID- 2186437 TI - [Neuroradiology in the pages of La Radiologia Medica. A survey of the work published in the 75 years of the existence of the journal]. PMID- 2186438 TI - [The role of echotomography in sports traumatology of the lower extremity]. AB - Sonography, which is commonly used in the evaluation of muscular traumas following exercise, quite often provides the radiologist with normal findings. One hundred and fifty-nine athletes were considered (170 US examinations), and the clinical diagnoses the patients had been referred for were compared with US findings: the pathologic condition was confirmed in 59% of the cases, while the extant 41% had normal findings. The highest percentage of positive findings was observed in the Achilles tendon region (75%), while the figure dropped to 38% in the thigh. In the latter location, muscular ruptures were confirmed in 69% of the cases, versus 17% in case of muscular distraction. As for the Achilles tendon, pathologic conditions both along the axis and in the insertion of the tendon were confirmed in 20% of the cases, but clinical accuracy was improved by US in 47% and 20% of the patients, respectively, and the diagnosis was changed in 10% and 20% of the cases, respectively. Therefore, clinical accuracy was demonstrated to depend on the pathologic condition as well as on the anatomical region involved. PMID- 2186439 TI - [The role of color Doppler echography in the diagnosis of breast tumors]. AB - The authors discuss the results from a series of 45 patients with breast lumps. All patients were studied by means of mammography, sonography, color Doppler US, and biopsy. Abnormal Doppler signal was observed in 94% of the patients with breast cancer. However, this finding is not specific because it can be occasionally found in benign lesions too. The use of color Doppler US is suggested in those cases where neither US nor mammography is conclusive. PMID- 2186440 TI - [The clinical utility of stereotaxic x-ray guided cytological biopsy in nonpalpable neoplastic pathology of the breast]. AB - The authors report the initial results of the combined use of stereotaxic X-rays and fine-needle aspiration biopsy in 83 patients with nonpalpable breast lesions. The stereotaxic system employed is a simple accessory of conventional mammographic equipment. Cytologic diagnosis (94 biopsies) had 90% sensitivity and 97% specificity; the percentage of acellular/insufficient cytologic samples was 10.8%. To assess the clinical value of this technique, the obtained results were compared with both mammographic findings and US-guided aspiration biopsy data. PMID- 2186441 TI - [A comparative evaluation of the centering precision performed with 2 different stereotaxic instruments in nonpalpable breast lesions]. AB - Two different instruments for nonpalpable breast lesion localization, with different patient position (prone and sitting), were evaluated in precision performances by measuring the mean needle deviation on X and Y axes in 150 and 100 examinations, respectively. Both instruments yielded precise information: some drawbacks were observed with the stereotaxic instrument fitted to the plain mammographic unit, due to imperfect fixation in the sitting position of the patient. The development of special seats could obviate the problem, thus allowing a further improvement in the performance of this kind of instruments. PMID- 2186442 TI - [Echography in the study of adenopathies of the upper abdomen]. AB - Four-hundred eighty-five patients underwent US examination; 183 of them had gastric cancer, 239 colorectal cancer, 38 pancreatic cancer, 11 esophageal cancer, and 14 had gastric lymphoma. All patients underwent surgery. In 95 cases fine-needle biopsy under US guidance was performed. Lymphadenopathies were classified by the criteria proposed by Yoshinaka et al., type I: poorly-defined borders, diffuse internal echoes; type II: well-defined borders, diffuse internal echoes; type III: well-defined borders, notchings, strong internal echoes. Twenty/twenty-nine type I, 66/98 type II, and 39/43 type III adenopathies were found to be neoplasm-positive. Of 73 patients with adenopathy from gastric cancer, 9 were type I, 42 were type II, and 22 were type III (183 patients examined); of 9 patients with adenopathy from esophageal cancer, 7 were type II and 2 were type III (11 patients examined); of 48 patients with adenopathy from colorectal cancer, 5 were type I, 28 were type II, and 15 were type III (239 patients examined); of 29 patients with adenopathy from pancreatic cancer, 7 were type I, 18 were type II, and 4 were type III (38 patients examined); finally, of 11 patients with adenopathy from gastric lymphoma, 8 were type I, and 3 were type II (14 patients examined). The relationship between US and pathology was possible from a statistical point of view only. Type I lymphadenopathies seem to suggest lymphomatous involvement, whereas type III ones suggest metastatic involvement. US is a valid approach method, which must be supported by other investigation techniques--e.g., CT and lymphography--in order to avoid high false-negative percentages. PMID- 2186443 TI - [The echographic diagnosis of acute appendicitis and its complications]. AB - The authors report their experience with emergency US in patients hospitalized for clinical suspicion of acute appendicitis or presenting with pain in the right lower abdominal quadrant. One hundred fifty-two patients were examined with US: 93/152 had pathologies of the right iliac region; 81 of them underwent surgery (50/81 appendectomies). In 27 of these patients the inflamed appendix presented with a typical US pattern. All of them had surgical confirmation. In 13/50 cases, US findings followed an atypical pattern (6 patients had a periappendiceal mass in the right iliac region, 3 had small amounts of fluid in the Douglas pouch, and 4 had gas-filled bowel loops of the ileum). The false negatives were 10/50. US sensitivity was 80%, and its specificity was 54%. The most common pathologic conditions are described whose symptoms mimic those of acute appendicitis. US role in inflamed acute appendicitis is still to be defined. Nonetheless, the authors suggest that US be performed on all patients with atypical pain in the lower abdominal quadrants, because of its high diagnostic accuracy in many common pathologies mimicking appendicitis, especially urinary and uterine adnexal pathologies. PMID- 2186444 TI - [Echography in the study of sialolithiasis]. AB - The US results are reported of 38 patients affected with sialolithiasis of the major salivary glands (37 cases of submandibular and 1 of parotid location). Sonography allowed all intraparenchymal calculi to be detected, as well as 59% of intraductal calculi. Associated US pathological features were: gland swelling in 36 cases (94%); ductal ectasia in 14 cases (61%); irregular echo structural arrangement of glandular parenchyma in 3 patients with multiple stones. US can be considered an useful diagnostic tool in sialolithiasis, for it allows the alterations in glandular structure in the late stages to be evaluated. Moreover, it may be repeated as often as necessary in the cases with multiple and/or recurrent stones. PMID- 2186445 TI - [Impedance plethysmography, Doppler echography and phlebography in deep venous thromboses of the lower limbs]. AB - Computerized impedance plethysmography (CIP) and phlebography were performed on 165 consecutive outpatients with clinical suspicion of deep venous thrombosis (DVT) and on 220 consecutive asymptomatic patients hospitalized for hip fracture. Ninety-two asymptomatic patients were examined also with real-time B-mode US. In orthopedic patients CIP sensitivity, specificity, accuracy, positive and negative predictive values were 19.4%, 90.5%, 64.4%, 53.8% and 66.3%, respectively, for proximal and distal DVT, versus 19.7%, 88%, 77.5%, 77% and 86% for proximal DVT. In symptomatic patients CIP sensitivity, specificity, accuracy, positive and negative predictive values were 83%, 87%, 85%, 87% and 82%, respectively, for proximal and distal DVT, versus 91%, 88%, 89%, 82% and 94% for proximal DVT. CIP had great diagnostic utility in symptomatic DVT, whereas its diagnostic efficacy was low in asymptomatic patients. In orthopedic patients US sensitivity, specificity positive and negative predictive values were 44%, 99.2%, 95.7% and 81.6%, respectively. US diagnostic value was relatively high, but further investigation is needed. To date, phlebography seems to be the only effective method in the diagnosis of DVT in asymptomatic high risk patients. PMID- 2186446 TI - [Transrectal echography and cystography in the assessment of female stress urinary incontinence]. AB - The authors report their experience in the study of urinary stress incontinence, by evaluating both affinities and differences between conventional techniques (cystography) and transrectal US. The parameters are evaluated concerning the relationship of the vesical cervix to the inferior margin of the pubis, together with the posterior urethrovesical angle (PUV), and the urethral inclination axis (AV). Twenty-five women with urinary stress incontinence were studied, and 20 subjects with different pathologic conditions. No single parameter considered appeared to be conclusive: as a matter of fact, both methods offer advantages and disadvantages, which are described. PMID- 2186447 TI - [An echographic study of a case of extramedullary plasmacytoma of the testicle]. PMID- 2186448 TI - [A calcified thrombus of the vena cava inferior in lupus nephropathy]. PMID- 2186449 TI - [Isolated voluminous varix at the splenic hilum. Its diagnosis by Doppler echography]. PMID- 2186450 TI - [Significance and implications of the anomalies in transmembrane transport of sodium in essential arterial hypertension]. AB - There is now some sort of agreement between different investigators regarding red blood cell Na+ transport in essential hypertension. This concerns at least two points: a) Na+ transport function is abnormal in erythrocytes from an important number of essential hypertensive patients, and b) the population of hypertensive patients is heterogeneous with respect to the different abnormalities in Na+ transport function. In contrast with the very large number of fundamental studies of Na+ transport in erythrocytes from essential hypertensive patients, very little is known concerning the clinical relevance of these findings. This review focuses on the etiopathogenic and pathophysiologic meaning of Na+ transport abnormalities which may be useful to the diagnosis and/or treatment of hypertensive patients. PMID- 2186451 TI - [Situation and new aspects in arterial hypertension in Spain]. AB - This paper briefly presents the situation of high blood pressure in Spain, both its prevalence in different parts of the country and its relevance as a cardiovascular risk factor and its relationship with demographic characteristics and other not removable risk factors. The association high blood pressure/hypercholesterolemia is discussed in greater detail, offering a multifactorial and quantitative approach of risk factors in the prevention of cardiovascular diseases. PMID- 2186452 TI - [Hemodynamics of arterial hypertension]. AB - Arterial blood pressure depends on the flow rate and peripheral resistances. Arterial blood pressure is regulated in arterial hypertension (AHT) in a very similar fashion as in normotensive subjects, but the peripheral vessels do not respond properly to increases in the cardiac output. The adrenergic nervous system plays a basic part in the mechanisms which provoke and regulate the AHT. The AHT usually begins with an increase in adrenergic tone and cardiac output: hyperkinetic hypertension. It later develops into an intermediate, normokinetic situation with latent left ventricular malfunction and finally augmented peripheral resistances which will become of organic character in time due to autoregulatory mechanisms. PMID- 2186453 TI - [Methodology problems in the study of arterial hypertension]. AB - This text deals with the methodological problems researchers have to face when trying to determine and study blood pressure (BP). It describes the measuring methods, the apparatus and the equipment used as well as the recording procedures and their technical shortcomings, together with their most common errors. It also deals with the various special problems involved. Ambulatory BP recording has greatly contributed to the significantly increased knowledge gained about the changeability of BP and the physiological, pathological and therapeutical factors which induce it. Even though, this technique may also have its limitations and may be subject to errors, its application is becoming more widespread, and its future enhancement will no doubt change the light under which we see BP today. I high BP recording is not only a sign on which the common AHT syndrome is normally diagnosed, but its prognosis value has also been known for years. Finally, because of the frequent epidemiological studies on BP, the prevalence of AHT in the various populations, likely therapeutical influences (therapeutical trials), etc., a close look at the methodological aspects of BP recording should be worth while considering. PMID- 2186454 TI - [Arterial hypertension in special situations: mild, systolic and in pregnancy]. AB - Mild hypertension is very common, 50% of hypertensives being with their diastolic BP between 90 and 104 mmHg. Many large studies, especially HDFP, had shown not only the deleterious cardiovascular effects of mild hypertension but also the benefits obtained with the therapy. The non-pharmacological approach should be the first step in the treatment of mild hypertension. Isolated systolic hypertension have a high prevalence in the elderly, increasing the cardiovascular morbidity and mortality. Sodium restriction and, if necessary, vasodilators increasing the arterial compliance seem to be the logical approach to treat isolated systolic hypertension. Finally, eclampsia is the most serious complication of pregnancy - induced hypertension. The treatment with bed rest and either betablockers or methyldopa is beneficial. If eclampsia occurs hydralazine, magnesium sulphate or nifedipine should be used. PMID- 2186455 TI - [Differential diagnosis of secondary arterial hypertension]. AB - The adequate performance of the differential diagnosis will permit us to classify any increase in blood pressure as due to primary or secondary causes. The data obtained in the clinical history and physical examination as well as those obtained through the minimal laboratory tests to be performed are the clues to identify secondary causes of arterial hypertension. PMID- 2186457 TI - [Echo-endoscopy: a new technic in the study of the digestive tract]. PMID- 2186456 TI - [Effect of antihypertensive therapy on the prevalence of ischemic cardiopathy in arterial hypertension. New contributions]. AB - Because hypertension is a major risk factor for cardiovascular disease it would be expected that therapeutic reduction of blood pressure would protect patients from coronary heart disease (CHD). Twelve long-term trials involving over 40,000 patients have been performed to study the effectiveness of diuretics and beta blockers in controlling blood pressure and reducing cardiovascular morbidity and mortality. However, no other drugs have been tested. The Hypertension Detection and Follow-up Program, European Working Party in the Elderly and the Metoprolol Atherosclerosis Prevention in Hypertension trial were the only studies where a significant reduction in total, cardiac and cardiovascular mortality were observed. Moreover three large trials have demonstrated some reduction in CHD among male nonsmokers. This review examines all these trials as well as some of the reasons for this disappointing outcome. New trials using modern antihypertensive drugs should be performed to analyze whether they contribute directly to protection from coronary events and other cardiovascular complications. PMID- 2186458 TI - [Hepatobiliary manifestations in AIDS]. PMID- 2186459 TI - [History of medicine. Souvenirs and the tales of 2 anesthetists from their beginnings in Liege]. PMID- 2186460 TI - [What is your roentgen diagnosis? intra- and retroperitoneal lymphadenopathy in advanced AIDS]. PMID- 2186461 TI - [ERCP in bile duct dilatation with jaundice due to spontaneous hydatid cyst rupture. Diagnosis, differential diagnosis, therapy and result]. AB - We report the case of a 17 years old Turkish patient hospitalized for colics and jaundice. Ultrasound, computer tomography and ERC showed enlarged intra- and extrahepatic bile ducts. The further investigations documented the rupture of a hepatic hydatid cyst into the biliary tract with obstructive jaundice. Other causes of jaundice as cystic duct malformation, calculi, tumours could be ruled out by surgery and histology. Etiology, diagnosis and treatment of hydatid jaundice are discussed. PMID- 2186462 TI - [Current possibilities in radiology for the diagnosis and therapy of gastrointestinal hemorrhage (roentgen diagnosis, nuclear medicine and interventional radiology)]. AB - Especially in acute gastrointestinal bleeding, conventional x-ray examinations with barium sulfate contrast are obsolete. On the other hand, blood pool scintigraphy and selective angiography are efficient methods to localize bleeding sources that have not been identified by prior endoscopy. In the interval between acute bleeding episodes, only vascular or highly vascularised lesions--as aneurysms, angiomas and leiomyomas--can be demonstrated. In all other lesions, active bleeding during the examination is a prerequisite. Angiography has not only a diagnostic, but also a therapeutic potential. By preoperative hemostasis, the circulatory conditions of the patient can be stabilized and surgery can be performed with a lower mortality risk. In "poor risk" patients, transarterial therapy can replace surgical interventions. PMID- 2186463 TI - [Cancer treatment using Dr. Moerman's diet and therapy. Documentation No. 24]. AB - For prophylaxis of cancer and treatment of manifest cancer Morerman recommends as the basis of his therapy a lactovegetable diet and, in addition, the '8 essential substances': vitamins A, B, C and E, iodine, sulfur, iron and citric acid. At a later stage he also recommends supplementary vitamin D and selenium. The most important aspect is the change in dietary habits required by the diet prescribed by Moerman and the ingestion of the '8 essential substances' in the form of conventional preparations. The daily cost of treatment of a prostatic cancer, for instance, ranges from about Fr. 3.- to Fr. 6.-. Side effects are not mentioned. The diet and therapy were developed by the Dutch physician Dr Moerman (1893-1988) as long ago as the 1930s. The promoters are the iridiologist J. Landman, the nutritional consultant E. Wannee and the writer R. Jochems. All three have written a book on Moerman. In Switzerland, the Lifecare Association endeavours to disseminate this form of therapy. A chronic deficiency of the '8 essential substances' is said to lead to metabolic disturbances, structural and behavioural anomalies of the regeneration tissue and alkalosis, which is claimed to be a fertile soil for the 'symbionts' that can transform healthy cells into cancer cells. Moerman came to this conclusion on the basis of his observations of pigeons. By means of a lactovegetable diet and substitution of the '8 essential substances', this metabolic disorder is said to be reversible, thus robbing the 'symbionts' of their growth medium. The results of the experiments with pigeons have, as far as we know, never been published.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186464 TI - [Rhinitis: current aspects in physiopathology and therapy]. PMID- 2186465 TI - [Rhinosinusitis: optimal medical treatment]. PMID- 2186466 TI - [Study of immunological deficiency]. PMID- 2186467 TI - [Usefulness of echography in the diagnosis of hip dysplasia in infants: prospective study in a regional hospital and literature review]. PMID- 2186468 TI - [The inauguration of the Institute of the History of Medicine and Public Health]. PMID- 2186469 TI - The clinical use of cocaine in rhinosurgery: a case-report and a review. AB - Three patients with adverse reactions of the nasal mucosa after topical anaesthesia with crystalline cocaine in combination with adrenaline are described. The current knowledge of the pharmacology of cocaine is summarized. The systemic and local reactions and side-effects of cocaine as topical anaesthetic in rhinosurgery are reviewed. PMID- 2186470 TI - [Meckel's diverticulum---clinical picture, diagnosis and treatment]. AB - Meckel's diverticulum is the most common anomaly of the gastrointestinal tract. It is usually asymptomatic, but it can cause rectal bleeding and bowel obstruction in both children and adults. Different investigative methods are used to diagnose Meckel's diverticulum. When a Meckel's diverticulum is suspected to cause rectal bleeding in children, the first choice of examination is the Meckel scan. Angiography is an alternative method in adults. Demonstration of a Meckel's diverticulum using barium meal examination is rare, but enteroclysis has been stated to be the most accurate method in detecting Meckel's diverticulum and other focal abnormalities of the small bowel. PMID- 2186471 TI - [Duplex sonography: a highly echogenic splenic cyst or splenomegaly?]. AB - A 27-year old woman presented sonographically with a highly echogenic mass in the left upper quadrant of the abdomen measuring 22 cm in diameter, initially interpreted as splenomegaly. Movement of internal echoes by application of pulsed doppler and by postural change of the patient revealed this mass as a cystic lesion with highly echogenic fluid. At surgery, a pseudocyst of the spleen containing detritus and cholesterol crystals was found. PMID- 2186473 TI - Abnormal intestinal permeability in Crohn's disease. A possible pathogenic factor. PMID- 2186472 TI - [A mucocele of the appendix--a case report]. AB - Mucoceles are rare lesions in the region of the appendix and occur in only 0.4% of all tumours of the appendix. Although their radiological-morphological pattern varies, a correct preoperative diagnosis is nevertheless possible in most cases via imaging methods and taking the pattern of clinical findings into consideration. PMID- 2186474 TI - Influence of the degree of liver failure on portal blood flow in patients with liver cirrhosis. AB - Portal vein haemodynamics as demonstrated by the pulsed Doppler system were studied in 37 patients with cirrhosis who had been classified in three groups (A, B, and C) in accordance with the degree of liver failure. Maximal inner diameter of the portal vein was significantly lower in patients who were considered to be in good condition (group A) than in patients with moderate and severe liver failure (group B and group C) (p less than 0.001). A significant difference was also found between group A and group B and between group A and group C with regard to the portal blood velocity and portal blood flow (p less than 0.001). In accordance with the presence and size of the oesophageal varices, in patients with large varices the portal blood velocity and portal blood flow were significantly lower than in patients without varices (p less than 0.001), whereas maximal inner portal vein diameter was significantly higher (p less than 0.001). This study demonstrated that in patients with cirrhosis circulatory alterations in the portal vascular bed may be, at least in part, an indicator of the stage of liver disease. PMID- 2186475 TI - Effect of bile on peritoneal morphology in Escherichia coli peritonitis. AB - To investigate whether bile within the abdominal cavity changes the morphologic expression of peritonitis, rats received intraperitoneal injections of saline, bile, Escherichia coli (3 x 10(8) colony-forming units), or E. coli and bile (n = 10 in each group). Specimens were taken from the parietal and visceral peritoneum for light microscopy and scanning electron microscopy, 10 h after induction of peritonitis. Bile alone increased the number of inflammatory cells, especially of the monocytic type. After E. coli alone the monocytic cell response was less pronounced, whereas the polymorphonuclear leukocyte response was comparatively large in the visceral peritoneum. Addition of bile in E. coli peritonitis caused a substantial increase in polymorphonuclear leukocytes, especially in the visceral peritoneum, and in the depth of the inflammatory cell reaction. At scanning electron microscopy mesothelial cells appeared normal after bile alone, had reduced numbers of microvilli after E. coli alone, and were denuded or separated, without microvilli, after E. coli and bile. It is concluded that the inflammatory effects of E. coli are greatly enhanced in the presence of bile. PMID- 2186476 TI - Effect of MaxEPA in patients with SLE. A double-blind, crossover study. AB - Seventeen patients with moderately active SLE participated in a double-blind, crossover study on the effect of MaxEPA, using olive oil as the control substance. During the first 3 months, 8/17 on Max EPA but only 2/17 on the control substance clinically and serologically improved (p = 0.05), but at 6 months there was no difference. The beneficial effect (if any) of MaxEPA on the disease was short-lived. PMID- 2186477 TI - Thoracic spinal hyperostosis in an early mediaeval skeleton. PMID- 2186478 TI - Generalized urticarial eruption during azathioprine treatment for rheumatoid arthritis. A case report and review of the literature. PMID- 2186479 TI - [Colonic fermentation: physiological review and role in digestive pathology]. AB - Diarrhea "with" bacterial fermentation is characterized by acidic liquid stools containing high amounts of organic acids. Disaccharide malabsorption is the main cause. The mechanism of diarrhea is osmotic, and colonic fermentations reduce diarrhea. It is unlikely that starch malabsorption induces significant diarrhea, whereas a high-fiber diet is responsible for "physiologic" diarrhea. Colonic fermentations increase diarrhea due to organic colitis and the "motor diarrheas". They may be responsible for some intestinal symptoms in patients with irritable bowel syndrome. This does not imply a "hyperfermentative" process due to a hypothetical disturbance of colonic microbial ecology. PMID- 2186480 TI - [Surgical therapy of severe idiopathic constipation]. AB - Because surgery for severe idiopathic constipation is seldom indicated, careful preoperative evaluation is mandatory (colonoscopy with biopsy, whole gut transit study, evacuation proctography, electromyography, anorectal manometry) in order to classify chronic idiopathic constipation into two broad functional groups: "outlet obstruction" and "colonic inertia". Subtotal colectomy with ileorectal anastomosis yields a good outcome in 70-100% of cases with slow transit constipation. In contrast, there is a broad spectrum of surgical techniques in the treatment of outlet obstruction, among which anorectal myectomy seems to be appropriate for selected patients with good results in 54-92%. Our own small surgical experience with chronically constipated patients (n = 4, 1987-1989) is discussed and compared with the results in the literature. PMID- 2186481 TI - [Abdominal actinomycosis--ileo-vaginal fistula as clinical manifestation. Case report and literature review]. AB - In 1985 sigmoid resection was performed in an 81-year-old patient with recurrent sigmoid diverticulitis. Due to adenomyosis uteri, hysterectomy was performed at the same time. Approximately one year after an uneventful recovery fetid leukorrhea occurred. Radiograms revealed a fistula between the terminal ileum and vagina. Adhesions between the terminal ileum and vaginal stump were surgically resolved and an ileum segment resection was performed. Postoperative recovery was uncomplicated and the patient has been symptom-free since. The histological findings of Actinomyces microorganisms, thread-like foreign material and detritus drew our attention to a rare instance of abdominal actinomycosis. Publications of purely historical interest dealing with therapeutic measures before the antibiotic era are not taken into consideration. The clinical picture, incidence and therapy of abdominal actinomycosis are described in the light of the literature. PMID- 2186482 TI - [Postoperative course following stomach resection: a comparison of Billroth I, Billroth II and Roux-en-Y resection-reconstruction]. AB - 53 patients who underwent gastric resection and reconstruction either by Roux-en Y gastro-jejunostomy, Billroth I or Billroth II operation, were followed for an average of three years and compared for clinical status using the Visick grading system, dumping grading by the method of Sigstad, and careful clinical questioning regarding post-gastrectomy symptoms. Response to a standardized questionnaire and objective grading showed that our results for individual operations compared well with others reports. However, the Roux-en-Y reconstruction showed significantly better results when compared to Billroth I, and especially Billroth II, reconstruction. It is concluded that partial gastrectomy with Roux-en-Y reconstruction is the preferred approach, provided that, in the light of the pathology encountered at operation, the procedure is technically feasible and adequate. PMID- 2186483 TI - [Is a pharmacological treatment of liver cirrhosis possible?]. AB - Loss of hepatic function is the limiting factor in survival of patients with cirrhosis. Fibrogenesis, cytolysis/necrosis and sinusoidal capillarization, altered composition of biomembranes, and hyporegeneration are identified as major factors in loss of hepatic function. Fibrogenesis has been successfully treated with colchicine. Cytolysis/necrosis in autoimmune hepatitis has for years been treated successfully with steroids: in postviral chronic hepatitis the interferons are showing high promise. Treatment of the other factors is the subject of intensive basic and clinical research. PMID- 2186484 TI - Connective tissue metabolism and hepatic fibrosis: an overview. PMID- 2186485 TI - Structure of the extracellular matrix in normal and fibrotic liver: collagens and glycoproteins. AB - The sketches in Figures 11 and 12, necessarily simplified, summarize some of the points discussed in the previous paragraphs. It can be concluded that the hepatic ECM and the ECM in general is a complicated supramolecular assembly of numerous defined macromolecules, each of which is endowed with a specific potential for interactions with one another and with various cell types. This matrix not only adapts rapidly to slight metabolic changes of the cells producing it, but also itself modulates the biochemical and morphologic phenotype of the cells anchored to it. Since mesenchymal cells appear to be the major source of hepatic ECM proteins in health and disease, it follows that the mesenchyme determines to a significant degree the phenotype of liver epithelial cells. Based on the growing knowledge of the hepatic ECM, immunoassays for ECM proteins or peptides in serum may provide information about the dynamics of fibrogenesis or fibrolysis in individual patients on a day to day basis, or permit detection of derangements of the hepatic ECM before they become clinically apparent. The clinical value of such assays is already being studied. Finally, knowing the molecules and the cells involved in ECM pathologic states offers us the tools to develop a specific targeted antifibrogenic therapy. PMID- 2186486 TI - Cellular sources of collagen and regulation of collagen production in liver. PMID- 2186487 TI - Cellular sources of noncollagenous matrix proteins: role of fat-storing cells in fibrogenesis. AB - The main types of noncollagenous ECM proteins in liver are FN, laminin, PGs and elastin. Also present is a pure carbohydrate polymer, hyaluronic acid. Their concentrations increase during fibrogenesis in a specific sequence and spatial distribution. FN is among the first to appear. The accumulation of matrix proteins in the space of Disse (perisinusoidal fibrosis) is most important for some clinical consequences of fibrosis. Perisinusoidal FSC are the cell type responsible for exaggerated ECM formation at sites of tissue injury, since these cells synthesize at a high rate in vitro all the noncollagenous matrix components occurring in fibrotic liver matrix (FN, laminin, dermatan sulfate, chondroitin sulfate, hyaluronic acid) and since FSC proliferate and transform into myofibroblast-like cells with an enhanced matrix protein synthesis rate. Recent experimental data suggest strong cellular cooperation of these cells with activated liver macrophages or Kupffer cells, platelets, and regenerating hepatocytes, which leads via a paracrine mechanism involving TGF beta, TGF alpha/EGF, PDGF, and probably other cytokines to stimulated proteoglycan synthesis, proliferation, and transformation into myofibroblast-like cells. The latter cell type has the potential of auto-stimulation (by an autocrine process) involving secretion of TGF beta and TGF alpha/EGF. Based on these findings, a model of FSC activation is proposed (Fig. 10). PMID- 2186488 TI - Matrix degradation in the liver. PMID- 2186489 TI - Hepatic fibrosis caused by alcohol. AB - The past decade of research has brought us closer to an understanding of the mechanisms whereby alcohol promotes fibrosis in liver. The perivenular and perisinusoidal fibrosis that characterizes alcoholic cirrhosis suggests that it is a unique entity, distinct from other types of fibrotic liver disease. On a cellular level, though, the target population and the regulatory events that control fibrogenesis may be typical of all types of fibrotic liver disease. The putative pathways to alcoholic fibrosis are exemplified in Figure 1. Fibrosis can be either the direct result of a stimulus from ethanol or one of its metabolites to a target cell population, presumably the lipocytes, or it can begin indirectly in response to hepatic inflammation. The indirect pathway to hepatic fibrosis is likely to be initiated by cytokines, elaborated by inflammatory cells. In addition, invasion of the liver by inflammatory cells may disrupt the normal hepatic extracellular matrix, which may in itself act as a stimulus for fibrogenesis by altering critical cell-matrix interactions. If alteration of the normal hepatic matrix is sufficient to promote fibrogenesis, it may act as a fixed stimulus that perpetuates fibrogenesis in the absence of ongoing inflammation. This may explain the progression of alcoholic fibrosis in some patients in the apparent absence of alcoholic hepatitis. It has been gratifying to observe a consensus emerge among experimental observations regarding the process of alcoholic fibrosis. In particular, the discovery of transitional cells in fibrotic liver tissue, and their relationship to lipocytes, correlates well with studies documenting activation of lipocytes in culture to a fibrogenic phenotype.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186490 TI - Therapy for hepatic fibrosis. AB - Although there is no established therapy for the fibrogenesis of hepatic cirrhosis, many potential therapies are now emerging. The requirements for the "perfect therapy" for hepatic fibrosis can be listed: (1) the pharmacologic agent should be active only in the liver; (2) its effect should be specific for collagen (or another critical extracellular matrix component); and (3) it should not be toxic. To date no agents fulfill these criteria. Of the agents we reviewed, only colchicine appears sufficiently safe for use outside of controlled clinical trials for cirrhotic patients whose underlying disease is not otherwise treatable. However, confirmation of the efficacy of colchicine in additional well controlled clinical trials is still required. Agents such as collagen propeptides require extensive in vitro development, while trials in animal models are required for prolyl 4-hydroxylase inhibitors, proline analogues, and prostaglandins. For more developed agents, such as malotilate and gamma interferon, there is now a need for well-designed long-term clinical trials. PMID- 2186491 TI - Work and mental health. Personal, social, and economic contexts. AB - This paper offers a critique of the prevailing view of the relationship between work and mental health. The critique is based on an examination of the personal, social, and economic contexts of work, especially in regard to people with serious mental illnesses. The paper concludes with a discussion of the implications of these contexts for necessary changes in social structures, attitudes, and vocational rehabilitation efforts. PMID- 2186493 TI - [The fluorescent antibody method in the diagnosis of hepatitis B virus infection in glomerulonephritis patients]. AB - In 107 patients with glomerulonephritis (GN) (28 were with acute and 79 with chronic GN) and 54 patients afflicted with other diseases of the kidneys, peripheral blood leukocytes were examined for HBsAg by indirect immunofluorescence. In 60 patients with GN and 32 patients with other diseases, blood sera were examined for HBsAg and anti-HBs by enzyme immunoassay along with examination of blood leukocytes for HBsAg. In blood leukocytes of GN patients, HBsAg was detected in 23.4% of cases, whereas in patients afflicted with other diseases of the kidneys, in 5.6% of cases. In the blood serum, HBsAg was also demonstrated more frequently in GN patients (in 15% of cases) as compared to patients with other diseases of the kidneys (in 3.1% of cases). The rate of anti HBs demonstration did not significantly differ in patients with GN and in those suffering from other diseases of the kidneys. None of the examined patients both with GN and other diseases of the kidneys showed at a time HBsAg and anti-HBs in the serum or HBsAg in leukocytes and anti-HBs in the blood serum. HBsAg in leukocytes and in the blood serum was identified at a time only in one patient afflicted with chronic GN. PMID- 2186492 TI - [The hypereosinophilic syndrome in a child with endomyocardial fibrosis treated surgically]. AB - The authors describe the case-history of a 12-year-old patient with hypereosinophil syndrome, endomyocardial fibrosis of the left ventricle and dominating mitral valve insufficiency. By correction of the insufficiency, using a Carpentier ring, the authors achieved substantial improvement of the haemodynamics. One year after operation the patient is cardially compensated. PMID- 2186494 TI - [An assessment of the therapeutic efficacy of gene-engineered human alpha 2 interferon in patients with acute viral hepatitis B]. AB - The clinical trials of alpha 2-interferon (alpha 2-IF) (reaferon) in 412 patients with acute viral hepatitis B (AVHB) permitted the establishment of the optimal therapeutic dose and the schedule for the drug use. The drug tolerance appeared satisfactory on the whole. alpha 2-IF was found to have a beneficial effect on the clinical course of VHB. The relationship was established between the therapeutic effectiveness of the drug and the clinical variants of the disease as well as the time of drug administration. The highest clinical effect (in 86.3%) was attained as a result of early (before the 7th day of jaundice) use of alpha 2 IF in patients with the acute-cyclic pattern of VHB. That effect consisted in the reduction of the treatment period (by 6-8 days), in a 2-fold reduction of the incidence of HBs-antigenemia, in rapid stimulation of the IF system, and in the initially low activity of natural killers. If the drug was administered later, the positive clinical effect was detectable only in 61% of the patients. In cholestatic VHB, alpha 2-IF did not produce any therapeutic effect. PMID- 2186495 TI - [The characteristics of the clinical picture and treatment of nonspecific ulcerative colitis and Crohn's disease]. PMID- 2186496 TI - [Sucralfate: the agent of choice in the treatment of peptic ulcer?]. AB - As many as 72 patients with erosive and ulcerous injuries to the stomach and duodenum were examined for the clinical efficacy of antepsin (sucralfate). Of these patients, 42 were with duodenal ulcer, 10 with gastric ulcer and 20 with erosive gastroduodenitis). Antepsin exerted a beneficial effect on the painful syndrome and on ulcer and erosion healing. The coefficient of the therapeutic efficacy of antepsin in duodenal ulcer patients turned out to be equal to 2.67 that of gastric ulcer to 2.1 and that in patients with gastroduodenitis was 2.6. The drug did not produce any well-defined side effects. In some cases (8.3%), it caused the appearance or enhancement of constipation. Antepsin is indicated not only in ulcer disease but also in duodenogastric reflux, reflux gastritis and reflux esophagitis. PMID- 2186497 TI - [The ultrasonic diagnosis of chronic cholecystitis using the choleretic test]. AB - To raise the accuracy of ultrasonic diagnosis of chronic cholecystitis, it is suggested that the choleretic test designed by the author may be used, making it possible to study gallbladder extensibility. As many as 124 patients with chronic cholecystitis and 50 healthy persons were examined. In 63 patients, the diagnosis was verified morphologically after cholecystectomies. Chronic cholecystitis patients demonstrated the lowering of gallbladder extensibility, especially after atropine administration preceded by the use of dehydrocholic acid. Echography with the use of the choleretic test considerably raises the accuracy, efficacy, specificity and sensitivity of ultrasonic diagnosis of chronic cholecystitis. PMID- 2186498 TI - [Diffuse thickening of the gallbladder wall detectable during echography]. AB - Echographic examination of 3900 patients showed enlargement of the gallbladder wall in 3.5%. It was seen not only in cholecystitis but also in diffuse liver injury, portal hypertension, chronic heart failure and in other pathological conditions. Examples are given of 3 different sonographic versions of enlargement of the gallbladder wall. In some patients' groups (with diffuse liver injury, chronic heart failure, portal hypertension), a correlation was established between the thickness of the gallbladder wall and the diameter of the portal vein. It is assumed that echographic demonstration of the enlarged gallbladder wall in patients with diffuse liver injury may serve an early sign of portal hypertension. PMID- 2186499 TI - [The possible pathways for the formation of a pool of an acid-soluble blood plasma fraction in patients with diffuse suppurative peritonitis]. AB - In patients with diffuse purulent peritonitis, the total pool of an acid-soluble blood plasma fraction (ABPF) considerably increases as compared to that in normals (donors). The present paper is concerned with the role of proteolytic activity and lysis of bacterial cells and cells of different human tissues in the formation of the ABPF in patients with peritonitis. For this purpose the normals' blood and its separate components were treated with various enzymes (trypsin, pronase, chemotrypsin, papain, elastase, alpha-amylase) to measure the ABPF. The pattern of changes detectable on such a treatment was compared with the tendency of changes seen in patients with peritonitis. Measurements were also made of acid soluble fractions in suspensions of bacterial cells and cells of the pancreas, liver and heart muscle tissue of man. It has been found that on proteolysis of plasma proteins and membrane proteins of blood cells there form products contained by the ABPF. Such products formed in the greatest amount as a result of treatment with pronase. Products of the lysis of bacterial cells may be also contained by the ABPF of peritonitis patients. The possibility of detecting proteolytic degradation and cellular disintegration according to the spectral characteristics of separate fractions of the ABPF is discussed. PMID- 2186500 TI - Hematologic response to acute inflammation: the band neutrophil revisited. AB - The value of the routine visual (manual) 100-cell differential leukocyte count (DLC) as a screening test in asymptomatic individuals or in patients on admission without suspected distributional or morphologic abnormalities has been challenged in the medical literature. More recently, the usefulness of an increase in the band neutrophils or a "left-shift" in the manual DLC has also been in question. This article discusses the largest sources of error in the routine DLC, namely, cell-identification errors, distributional errors, and statistical sampling errors. The latest flow cytometric, cytochemical, automated leukocyte differential counters offer a viable, reliable alternative to the highly imprecise 100-cell DLC. Studies have shown that these newer instruments are sensitive in detecting the hematologic response to acute inflammation or infection and have the advantage of vastly increased precision and therefore of improved reliability of the differential leukocyte count. PMID- 2186501 TI - Dietary treatment of hypercholesterolemia. AB - Diet is the first line of treatment for hypercholesterolemia. Patients should be encouraged to make simple and stepwise changes in their diets to lower elevated cholesterol levels. General dietary guidelines from the American Heart Association (AHA) Step-One Diet include limiting the amount of total fat to less than 30% of total calories, decreasing cholesterol intake to less than 300 mg/day, and adjusting caloric intake to levels required to attain or maintain ideal body weight. Diets must be individualized to meet therapeutic needs within the limits of the patient's abilities, knowledge, and motivation. PMID- 2186502 TI - Early cancer detection: update for primary-care physicians. AB - This article highlights information about the importance of early detection of cancer in the primary care physician's office. It represents information derived from a cancer prevention reference manual, ReCap: Recommendations for Cancer Prevention, developed by the Department of Cancer Prevention and Control at The University of Texas M.D. Anderson Cancer Center. Production, evaluation, and distribution to all primary care physicians in Texas were funded by the Physician Oncology Education Program, a program of the Texas Medical Association funded by the Texas Cancer Council. PMID- 2186503 TI - [Aujeszky's disease in dogs and cats]. AB - Pigs are either directly or indirectly the source of infection with Herpes virus suis in dogs and cats. On oral or oronasal infection, the virus is spread by way of the cranial nerves to the central nervous system. The incubation period is short: from one to six days. The disease is mainly characterised by nervous disorders. Pruritus is a characteristic clinical sign but is not present in every case. Mortality in dogs and cats is a hundred per cent. In rural areas, infection is caused by consumption of uncooked pork or offal from pigs. Prevention is possible by avoiding exposure to pigs or fresh pig products. It is possible to vaccinate dogs and cats with an inactivated vaccine. Results of vaccination studies show some variation, however. PMID- 2186504 TI - [Preparation of vaccines]. AB - A historical review on the preparation and use of vaccines is presented. The example of smallpox vaccination in man is interesting, as it affords an insight into the development of the principle of vaccination, the improvement of the vaccine and the eradication of the disease. Moreover, the various stages of vaccinology were described. Initially, vaccines were prepared on the basis of the attenuated or inactivated pathogens. After the introduction of animal cell culture techniques among others it became possible to realise an amplification of the preparation of virus vaccines. Since the introduction of recent biotechnological methods, including monoclonal antibodies and recombinant DNA technology, the development and preparation of well characterised and purified vaccines became possible. Immunology, including the development of adjuvants and the immunogenetic aspects, is essential in the further development of vaccines. Furthermore, it should be stressed that in using vaccines, the control aspects of the new generation of vaccines including the application of so-called Good Manufacturing Practice (GMP), directives for their preparation should be strictly adhered to. PMID- 2186505 TI - [The work and influence of Hanns Langendorff]. PMID- 2186506 TI - [Special aspects of the quality control of gamma cameras]. PMID- 2186507 TI - [Radiation exposure during SPECT and possibilities of reducing the radiation exposure of patients and personnel]. PMID- 2186508 TI - [Biokinetics of radioactive substances and models for the calculation of radiation exposure]. PMID- 2186509 TI - [Radiation exposure during positron emission tomography (PET) and possibilities of reducing the radiation exposure of patients and personnel]. PMID- 2186510 TI - [Radiation protective measures for personnel involved in nuclear medical diagnosis]. PMID- 2186511 TI - [Lessening radiation exposure by the choice of a suitable radionuclide]. PMID- 2186512 TI - [Lessening radiation exposure by improving the organ specificity of radiopharmaceuticals]. PMID- 2186513 TI - [In memoriam Hans Detlev Roedler, 1943-1989]. PMID- 2186514 TI - [The determination of ABO system antigens in human hair]. PMID- 2186515 TI - Escherichia coli aspartate transcarbamoylase: the molecular basis for a concerted allosteric transition. AB - Aspartate transcarbamoylase from Escherichia coli has become a model system for the study of both homotropic and heterotropic interactions in proteins. Analysis of the X-ray structures of the enzyme in the absence and presence of substrates and substrate analogs has revealed sets of interactions that appear to stabilize either the 'T' or the 'R' states of the enzyme. Site-specific mutagenesis has been used to test which of these interactions are functionally important. By combining the structural data from X-ray crystallography, and the functional data from site-specific mutagenesis a model is proposed for homotropic cooperativity in aspartate transcarbamoylase that suggests that the allosteric transition occurs in a concerted fashion. PMID- 2186516 TI - How calmodulin binds its targets: sequence independent recognition of amphiphilic alpha-helices. AB - Calmodulin (CaM) is a protein capable of recognizing positively charged, amphiphilic alpha-helical peptides independent of their precise amino acid sequences; this structural feature has also been found in many CaM-binding proteins. Recent work involving crystallography and site-directed mutagenesis of CaM along with studies of photoreactive and fluorescent CaM-binding peptides have helped define how calmodulin interacts with amphiphilic helices. PMID- 2186517 TI - Antibody: the flexible adaptor molecule. AB - Antibodies are flexible adaptor molecules linking target and potential killer i.e. antigen and effector. With the discovery of effector binding sites on antibodies we can begin to visualize at the molecular level how this adaptor role is fulfilled. PMID- 2186518 TI - Turning on the respiratory burst. AB - The respiratory burst is a distinguishing property of phagocytes. It is induced by chemotactic stimulation or phagocytosis and reflects the activation of a membrane-bound enzyme system that transfers electrons from cytosolic NADPH to extracellular oxygen, producing superoxide. The products of the burst are essential for the killing of microorganisms, but are also a cause of tissue damage and inflammation. Studies aimed at a better understanding of the regulation of the respiratory burst should help in the search for new ways to treat infections and inflammation. PMID- 2186519 TI - Protein transport into and within chloroplasts. AB - The chloroplast is a complex organelle which carries out a wide range of metabolic processes such as light capture and the biosynthesis of carbohydrates, fatty acid and amino acids. This organelle consists of three separate membrane systems which enclose three distinct soluble phases. Most of the chloroplast proteins are imported from the cytosol and directed into the six different compartments. This import and intraorganellar sorting process makes the chloroplast an interesting and promising system for the analysis of how proteins interact with and are translocated across biological membranes. PMID- 2186520 TI - Marked differences between orthotopic and heterotopic auxiliary liver allografts in the induction of class II MHC antigens on hepatocytes. PMID- 2186521 TI - Evidence that anti-LFA-1 in vivo improves engraftment and survival after allogeneic bone marrow transplantation. AB - The LFA-1 molecule is a member of the leukocyte adhesion complex (CD11/CD18) that is critical to adhesion and effector function of T cells and NK cells. Both T cells and NK cells play important roles in bone marrow graft rejection, and anti LFA-1 MAbs inhibit in vitro T cell and NK cell cytotoxicity. We here describe the in vivo use of a monoclonal antibody to the alpha chain of LFA-1 (CD11a) to prevent rejection of T cell-depleted allogeneic bone marrow. Animals receiving anti-LFA-1 and 1100 cGy total-body irradiation showed improved hemopoietic and immunologic reconstitution one month after BMT when compared with animals receiving TBI alone. Animals in the anti-LFA-1 group showed significantly improved long-term survival, and had no deficits in long-term lymphohemopoietic reconstitution. PMID- 2186522 TI - Immunocytochemical changes suggestive of damage to endothelial cells during rejection of human cardiac allografts. AB - Interest in the endothelium as a possible initiator or target of the antiallograft response prompted the following study. Immunocytochemical techniques have been used to investigate the expression of the endothelial markers EN4, Pal-E, and FVIII-RA in normal human heart, cardiac biopsies from patients with various cardiac diseases (dilated cardiomyopathy [DCM] and myocarditis [MCO]), and cardiac biopsies from heart-transplant recipients undergoing acute rejection or free of rejection. Quantitative data demonstrated greater preponderance of EN4 cells in normal heart than the other markers. In biopsies showing histologic signs of rejection, there was no difference in the number of EN4 positive cells compared to normal. In contrast, there was found a striking increase in the proportion of cells that are Pal-E positive and a significant increase in the proportion of FVIII-RA positive cells in these biopsies. The patient details provided suggest these results do not reflect vascular damage due to cyclosporine but may well reflect damage caused by the rejection process. PMID- 2186524 TI - Adsorption of cytotoxic anti-HLA antibodies with HLA class I immunosorbant beads. AB - In an effort to generate HLA immunosorbants to specifically remove anti-HLA antibodies from sera of highly sensitized patients, we purified HLA proteins, covalently coupled them onto Sepharose, and adsorbed antisera from five patients with narrowly reactive cytotoxic anti-HLA antibodies and from one patient with broadly reactive antibodies. We found that an HLA-A2 immunosorbant depleted anti HLA-A2 cytotoxic antibodies, but did not deplete anti-HLA-B7 or anti-HLA-B44 cytotoxic antibodies from the narrowly reactive patient sera. Patient S.C. developed high PRA (81%) with strong cytotoxicity against HLA-A1 and -A2 following rejection of an HLA-A1, -B57 mismatched kidney. We adsorbed his sera with five HLA immunosorbants including HLA-A2 and HLA-A1,28. We found that the HLA-A2 immunosorbant depleted antibodies to HLA-A2+ and HLA-B57+ cells but not to HLA-A1+ cells, while the HLA-A1,A28 immunosorbant depleted antibodies to both HLA A1+ cells and to the HLA-A28 cross-reactive HLA-A2+ cells. Adsorption was specific for HLA-A alleles to which the patient was sensitized, since neither HLA B-C immunosorbants (containing HLA-B7, -B8, -B13, -B27, or -B37 plus HLA-C gene products) nor the control immunosorbants (bovine serum albumin or diphtheria toxoid) depleted serum S.C. of cytotoxic anti-HLA antibodies. Our results indicate that HLA immunosorbants are stable to sequential cycles of adsorption and elution, and thus may be of future therapeutic value in treatment of sensitized patients. PMID- 2186523 TI - Long-term, low-dose cyclosporine treatment of renal allograft recipients. A randomized trial. AB - Ninety-two adult renal allograft recipients, receiving baseline immunosuppression with CsA and prednisone, were assigned randomly to one of the following regimens. CsA was discontinued (D/C group) in 47 recipients who were then maintained on Aza and prednisone; or Aza was added to continued low-dose CsA and prednisone (triple drug [TD] group) in 45 patients. Entry into the study required an absence of rejection and a stable creatinine for at least four months prior to randomization. The mean month of randomization was 8.34 +/- 2.9 for the D/C group, and 7.2 +/- 3.2 for the TD group. Following randomization, a significantly greater rate of rejection (P less than .01) was observed in the D/C group (40%) than in the TD group (13%). With a mean follow-up of 30 months, 41/47 of D/C allografts (87.2%) and 39/45 TD allografts (86.6%) were functioning. Nevertheless, rejection had a persistent adverse effect on allograft function, in both the D/C and TD groups, up to 36 months following randomization. Parameters such as donor-type and rejection prior to randomization did not identify recipients at risk for rejection following randomization. Therefore, although the CsA withdrawal regimen might be ideal, the opportunity to select appropriate candidates remained elusive. In contrast, the safety of the TD regimen became apparent. Neither significant nephrotoxicity nor hypertension was observed, and the opportunity for less daily prednisone was evident. Despite its additional cost, the TD regimen utilizing indefinite low-dose CsA, is preferred. PMID- 2186525 TI - Analyses of development of insulitogenic T lymphocytes in NOD mice by transplantation of bone marrow, thymus, and pancreas. AB - To estimate the functional participation of the insulitogenic genes in the development of insulitogenic lymphocytes, we attempted to induce insulitis in normal allogeneic BALB/c hosts by bone marrow transplantation from NOD mice. The development of the insulitogenic lymphocytes was histologically examined using the host's pancreas and pancreatic tissue from NOD mice which had been grafted under the renal capsules 2 weeks before sacrifice. Adult-thymectomized NOD mice that had been reconstituted with the thymus and bone marrow from NOD mice showed insulitis in both the host's pancreas and grafted pancreatic tissue from newborn NOD mice. When BALB/c mice were lethally irradiated and then reconstituted with NOD bone marrow cells, no insulitis developed in the pancreatic grafts from NOD and BALB/c mice or in the host's pancreas. Since the specificities and functions of T lymphocytes are controlled by the thymic microenvironment during the differentiation within the thymus, the thymus of BALB/c genotype may be responsible for the failure to induce the insulitogenic lymphocytes. Therefore, athymic BALB/c mice were reconstructed with bone marrow cells and thymus of NOD genotype. No insulitis developed, however, in either the host's pancreas or grafted pancreatic tissue. These results suggest that the bone marrow cells and thymus of NOD genotype are not sufficient to induce insulitogenic lymphocytes in the allogeneic BALB/c environment. PMID- 2186526 TI - Immunocytochemical and ultrastructural changes of islet cells in rats treated long-term with cyclosporine at immunotherapeutic doses. AB - Daily cyclosporine doses of 10 mg/kg body weight for 21 days in Wistar rats cause impairment in glucose homeostasis and changes in the amount of immunostainable hormones and in the ultrastructure of the cells of the pancreatic islets. CsA induces hyperglycemia and reduced glucose tolerance, and causes a decrease in immunoreactive insulin and an increase of somatostatin and pancreatic polypeptide (PP) immunoreactivities, leaving glucagon immunoreactivity unaffected. Ultrastructurally, different degrees of dilation of rough endoplasmic reticulum cisternae and enlargement of Golgi apparatus can be observed in B cells, together with a pronounced reduction in the number of secretory granules. Nevertheless, there were no apparent morphological changes of the other cytoplasmic organelles, suggesting that the drug, besides a depression of protein synthesis, as previously stated, also induces a substantial defect in granulogenesis, probably due to impairment in the intracellular transport of the hormone from the sites of synthesis to the secretory granules. The B cell alterations are not accompanied by any sign of B cell degeneration or death. Non-B cells did not show any of the ultrastructural changes found in B cells and were similar to those of the control rats. The above findings indicate that CsA at immunotherapeutic doses causes impairment in the secretory processes of B cells specifically. An hypothesis on the mode of action of CsA on B cells is drawn. PMID- 2186528 TI - Dimers, leucine zippers and DNA-binding domains. AB - Transcription factors can be divided into classes on the basis of their mode of interaction with the target promoter sequence. Different protein domains responsible for DNA recognition have been identified. In this review we discuss the leucine zipper structure, which has been found in several nuclear factors, including the oncoproteins Fos and Jun. Structural considerations are summarized to help understand how dimerization is mediated by the leucine zipper and how this is the prerequisite for optimal target DNA recognition by the adjacent basic domains. PMID- 2186527 TI - HLA-class II antigen expression in human heart-lung allografts. AB - Long-term survival in heart-lung transplantation has ben hindered by the development of bronchiolitis obliterans (OB), which is believed to be a manifestation of chronic rejection of the lung. Since HLA-class II antigens are involved in the rejection response, the distribution of the class II products HLA DR, HLA-DQ, and HLA-DP were studied in normal lung, and in transplanted lung with and without OB, utilizing frozen-section immunohistochemical techniques. All three allelic products are usually expressed on the epithelial, endothelial, and mesenchymal components of the lung. Sequential transbronchial biopsies from 4 recipients before and concurrent with the diagnosis of OB were stained with serial dilutions of monoclonal antibodies to assess the level of expression of the above class II products. Increased levels of HLA-DR and HLA-DP antigens may be seen on the bronchial and bronchiolar epithelium during OB, but the changes are subtle and complicated by many other variables. Additional studies are needed to confirm these preliminary results. PMID- 2186529 TI - The structure and assembly of active chromatin. AB - Much effort has been expended towards understanding the details of how nucleosomes are established on newly replicated DNA. More recently it has begun to be possible to study the binding of both trans-acting factors and histones to DNA. This review is concerned with an assessment of the current status of this work. In addition, we discuss some of the questions that still need to be addressed in order to understand how trans-acting factors can establish extensive interactions with the DNA of active genes while they are excluded from inactive genes. PMID- 2186530 TI - Axial patterning and the establishment of polarity in the frog embryo. AB - We review the early development of the frog Xenopus laevis, concentrating on events that lead to the establishment of the body plan. Recent molecular and embryological experiments suggest that peptide growth factors and homeobox genes interact to specify cell fates and pattern during early development of this vertebrate. PMID- 2186531 TI - [The effect of insulin and thyroxine on the age-related dynamics of synthesis and degradation of proteins in skeletal muscles of cattle]. AB - The intensity of sarcoplasmic and myofibrillar protein synthesis in skeletal muscle homogenates of the cattle aged from 45 to 360 days is 3.5 and 3.8 times reduced, respectively, and remains at the same level in the old beef cattle aged 540 days. Exogenous insulin and thyroxin increases the sarcoplasmic and myofibrillar protein synthesis in skeletal muscle homogenates of animal at certain stages of postnatal ontogenesis. The catepsin and neutral protease activities are 2.0 and 1.7 times as low in the skeletal muscle of the cattle aged from 45 to 360 days while in the subsequent period they change slightly. Exogenous insulin decreases the catepsin protease activities but does not change the neutral protease activities in the skeletal muscle of animal at the most stages of postnatal ontogenesis. Exogenous thyroxin increases the catepsin and neutral protease activities in skeletal muscle of animals at the some stages of postnatal ontogenesis. PMID- 2186532 TI - [Methods of measuring the transmembrane electrical potential in cells]. AB - The methods of intracellular microelectrodes, penetrating ions and potential sensitive fluorescent probes are considered for their possibility to be used for quantitative estimation of transmembrane electrical potentials (TMP) of small cells (mainly through the example of lymphocytes). The following fluorescent methods are described in detail: separate measurement of two TMP components- potentials on the plasma and mitochondrial membranes of a cell; recording of individual differences of cells according to the TMP value. It is supposed that heterogeneity of cells by the TMP value (in particular, the presence of depolarized cells) may be responsible for errors and divergences of the TMP mean values measured by different methods. PMID- 2186533 TI - [Self-treatment at home for hemophiliacs]. AB - This study reviews the international literature on the efficacy of home self treatment for severe hemophiliacs. It is also based on a survey of the capacity of hemophilia network centers to reach their target clientele. Home self treatment is largely established in industrialized countries. It has been appreciated by hemophiliacs, particularly for the increased autonomy and quality of life generated. Hemophilia centers give them access to professionals who have developed a great expertise in this pathology. In Quebec, the vast majority of severely affected type A hemophiliacs are registered with a comprehensive care center for hemophilia. Very few hemophiliacs are still being treated exclusively in hospitals. PMID- 2186534 TI - Current concepts in the perinatal diagnosis and management of hydronephrosis. AB - Perinatal urology has become a significant facet of pediatric urologic practice. This article reviews the approaches to the diagnosis of prenatal hydronephrosis and its typical sonographic appearances in relation to the underlying pathology. A review of the outcomes of prenatal uropathology serves as a basis on which to interpret reports of prenatal intervention for hydronephrosis. A critical review of the experience of prenatal intervention is conditionally supportive of its benefits, but this view must be tempered by a recognition of the inherent risk to the mother and fetus. Included within this view is a recognition that not all hydronephrosis is caused by obstruction. More specific prognostic indicators of renal and pulmonary functional reserve are critically needed to permit appropriate patient selection. This must be coupled with more rigorous assessment of outcomes and complete reporting of the results. Continued basic and clinical research is important in developing these data. A management strategy for hydronephrosis in the prenatal and postnatal periods is presented, based on the goal of permitting maximal renal as well as pulmonary development in utero and in the newborn period. PMID- 2186535 TI - Contemporary techniques for the radioisotopic evaluation of the dilated urinary tract. AB - Regardless of one's approach to the evaluation of hydronephrosis, nuclear imaging should be part of every child's evaluation, as it is the only imaging modality capable of providing significant renal function information. The studies can easily be performed on an outpatient basis without sedation. Diuretic renal scintigraphy is deceptively simple to perform, and commitment to detail is exceedingly important if the results are to be valid. Radioisotope transit time may also be helpful, although its calculation is technically difficult. Determination of the function of the kidneys individually is possible by several methods. PMID- 2186536 TI - Management of the dilated obstructed ureter. AB - Megaureters have been classified as refluxing, obstructed, nonrefluxing nonobstructed, and refluxing-obstructed. The recommendations for the management of each type are fairly well agreed on. Where controversy has arisen is in the differentiation of the types, especially the primary obstructed from the nonrefluxing-nonobstructed. Distinguishing dilatations that represent significant obstruction from those that apparently are anatomic variants having no detrimental implications for renal function is no simple task, especially in the neonatal infant. PMID- 2186537 TI - Renal functional changes associated with vesicoureteral reflux. AB - The data cited have been intended to show that renal functional abnormalities are commonly associated with reflux. Tubular abnormalities, particularly concentrating defects, probably occur early, and glomerular dysfunction is a late manifestation. Problems with acid-base balance are uncommonly examined but may be more relevant clinically, because such abnormalities could affect bone growth. Fractional excretion studies are less sensitive than concentrating ability in indicating dysfunction. Associated pyelonephritis hastens renal damage and exacerbates any functional abnormality. Renal functional abnormalities are more common in patients with renal scarring and indeed may be predictive of a process that is not yet apparent pathologically. PMID- 2186538 TI - Physiology of lower urinary tract obstruction. AB - One of the major dilemmas facing pediatric urologists today is discerning obstruction in the dilated urinary tract. Apparently similar anatomic obstructions can result in very dissimilar consequences. The authors focus on the physiologic response of the bladder and upper tracts to infravesical obstruction. They caution against treatment focused merely on the obstruction, noting that the entire urinary tract must be addressed. PMID- 2186539 TI - Alternatives in the management of posterior urethral valves. AB - The child with posterior urethral valves poses a continuing treatment dilemma because congenital infravesical obstruction may result in long-standing dysfunction of all segments of the urinary tract. Relief of the obstruction may not return bladder pressure to normal or completely resolve abnormalities of ureteral drainage. Dysplastic renal parenchyma cannot recover. Four issues affect the identification of those children who will benefit from therapy beyond transurethral valve destruction: the concept of transitional nephrology, the possibility of coexisting ureterovesical obstruction, the valve bladder syndrome, and prenatal urology. PMID- 2186540 TI - Emergency treatment and long-term follow-up of posterior urethral valves. AB - Posterior urethral valves have a broad spectrum of clinical severity determined by the degree and reversibility of the long stepwise sequence of secondary pathology. Neonatal azotemia and severe bilateral reflux are particularly important negative prognostic factors. In the mild cases, valve ablation with or without delayed reconstruction is good therapy. In the very severe cases, our interpretation of all the clinical and experimental information now available suggests that the time interval and the level of decompression are extremely important. Achievement of consistent low caliceal pressure without stasis and infections should be achieved as soon as possible. We do not agree with the philosophy of "valve ablation and wait and see" for secondary reconstruction as applied to the severe cases. An analogous philosophy would be treating all respiratory infections as upper respiratory infections and applying aggressive appropriate therapy for pneumonia only if the patient does not respond clinically. However, all controversy aside, the management of neonatal infants with posterior urethral valves remains a difficult and challenging problem for us all. The real challenge will be to improve published management results to the point that the family faced with decisions regarding an in utero diagnosis of posterior urethral valves will have enough hope to continue the pregnancy. PMID- 2186541 TI - Early ureteral surgery for posterior urethral valves. AB - The obstruction caused by posterior urethral valves may be responsible for profound dysfunction of the entire proximal urinary tract. The pathophysiologic relations between the valves and function of the ureterovesical junction and upper urinary tract are key in determining the need for upper tract surgery. In most cases, function of the ureters and ureterovesical junction is directly related to high intravesical pressure and will normalize when pressures drop after valve destruction. However, upper tract function remains abnormal in some cases and leads to complications that necessitate early ureteral and upper tract surgical intervention. The second crucial relation in the management of patients with posterior urethral valves is that between renal dysfunction and urinary tract obstruction. The surgeon is compelled to maximize the potential for renal function. The relation between renal dysplasia, obstructive uropathy, and urinary tract obstruction complicates the management of patients with posterior urethral valves and challenges us to develop new methods to measure potential renal function. Patients born with posterior urethral valves are treated initially with bladder drainage, which is undertaken by placement of a urethral catheter at the time diagnosis is made with the voiding cystogram. During this initial period of evaluation and stabilization, the patient's medical status is optimized, giving the surgeon information concerning renal function and prognosis to allow the most efficient surgical management. In almost all cases, posterior urethral valves are destroyed primarily, most often by transurethral fulguration. This usually leads to rapid improvement of bladder, upper tract, and renal function. When primary fulguration is not advisable, drainage through a vesicostomy is a useful alternative. Utilizing either method, low-pressure bladder drainage is a primary goal in the initial management of patients in most centers. As with many problems in surgery, our ability to accurately identify patients who would benefit from surgery is more limited than our surgical effectiveness. Voiding cystograms allow us to diagnose reflux and to follow bladder emptying and function. Serial ultrasound scans, nuclear medicine scans, and pressure-perfusion studies give us insight into upper urinary tract function. Too often, however, limitations of the patient's condition and size and the severe degree of urinary tract abnormalities make the results difficult to interpret. Although diagnostic tests are invaluable in making decisions about upper tract surgery in patients with posterior urethral valves, these decisions are most often based on the classic clinical urologic problems of urinary extravasation, obstruction, infection, reflux, and azotemia.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2186542 TI - Management of the obstructed urinary tract associated with neurogenic bladder dysfunction. AB - The child with neurogenic bladder dysfunction may suffer from lower urinary tract obstruction, which, if untreated, can result in upper urinary tract deterioration. It is prudent to identify those newborns and infants who are at risk for upper urinary tract deterioration and advise an appropriate treatment protocol. In order to identify those children at risk, a thorough examination is required, along with appropriate upper urinary tract imaging studies and urodynamic assessment of the bladder. Infants and children at risk for upper tract deterioration are those who have intermittent or continuous detrusor pressure elevation above 40 cm H2O. We have identified the safe period, which is the time during which the bladder remains at a pressure lower than 40 cm H2O. Our management protocol for each child is individualized and based on increasing the safe period. The safe period can be increased with a combination of intermittent catheterization, administration of medications, and, in some cases, surgical reconstruction. With compulsive evaluation and intensive management, many of the previous upper urinary tract changes associated with the obstructed neurogenic bladder can be averted. With the above factors in mind, we have defined the period of bladder filling and storage where the pressure is below 40 cm H2O as the safe period. The ideal bladder for maintenance of normal upper tracts would have a long safe period and low voiding pressure. Our treatment protocol for the neurogenic bladder is therefore dependent on identifying those children who have very short or nonexistent safe periods. These are the children who are at risk for upper tract deterioration. PMID- 2186543 TI - Current management of the dilated urinary tract in prune belly syndrome. AB - Upper urinary tract stasis, poor bladder emptying, vesicoureteral reflux, and bacteriuria in various combinations are the factors that have led to a poor long term prognosis in patients with prune belly syndrome. Whether these factors are best controlled by medical treatment or by surgical correction has been the source of some controversy. Although medical treatment may have improved over the years, so have the results of reconstructive surgery. Because the syndrome is a spectrum disorder, there will certainly be many patients who require little or no surgical intervention. The majority, however, will benefit from carefully planned and well-executed reconstructive surgery. Even in these cases, there should be a period of medical treatment and surveillance with interval re-evaluation. In a few patients, early stabilization will not be possible, and a drainage procedure such as vesicostomy will be necessary in the first days of life. Regardless of how an individual patient might be treated, he will require long-term follow-up surveillance. As more long-term results are reported, the optimal treatment plan should become more obvious. PMID- 2186544 TI - Role of in-office ultrasonography in screening infants and children for urinary obstruction. AB - With the availability of machines suitable for the office, we studied whether in office ultrasonography could assist in the management of children with known or suspected hydronephrosis. Of 509 children examined, 81 (16 per cent) had hydronephrosis. In 56 (70 per cent) of these children, ultrasonography was helpful in expediting the diagnosis (9 cases), clarifying the etiology (16 cases), evaluating the condition postoperatively (26 cases), and screening (5 cases). Three incorrect ultrasound diagnoses were encountered. The authors believe that ultrasound is the best initial imaging method for the urinary tract and have shown that it is practical and effective in an office setting. PMID- 2186545 TI - Experimental congenital obstructive uropathy. AB - Continued experimental work in congenital obstructive uropathy is essential to support the rapidly advancing field of fetal medicine. It is possible to reproduce the clinically relevant obstructive lesions in an experimental model. On the basis of data from these models, the tentative conclusion is that in utero intervention is beneficial in severe congenital obstructive uropathy associated with oligohydramnios. The limited human experience provides insufficient data to confirm this hypothesis but has demonstrated the technical feasibility of prenatal interventions. There is a critical need for further refinement in understanding the complex pathophysiology of congenital obstructive uropathy, not only the renal consequences, but also the pulmonary and systemic effects. There remains the particular need to resolve the determinants and indicators of functional salvageability of the kidneys and lungs in congenital obstructive uropathy. PMID- 2186547 TI - [Ultrasonic examination in the diagnosis of closed trauma to the kidney]. AB - Ultrasonic investigations (USI) were used in the diagnosis of closed renal injuries in 59 patients (51 males and 8 females) aged from 17 to 65 years. The lesion of the right kidney was diagnosed in 35 (59.3 per cent) patients, the left kidney was affected in 24 (40.7 per cent) of examinees. In 2 persons the injury of the kidney was combined with the lesion of the urinary bladder. According to USI results, the patients with suspected closed trauma were enrolled in 4 groups: persons with an intact renal parenchyma, fibrous capsula and pelvicaliceal renal system (the contusion of the kidney); persons with normal ultrasonic picture of the kidney and the presence of intermuscular hematoma; those with subcapsular hepatoma; and those with pararenal hematoma. USI technique turned to be high informative in the diagnosis of the occult renal injuries and permitted evaluating the structure of the kidney, the character and degree of the lesion and following up the status of the compromised organ during the conservative treatment. PMID- 2186546 TI - [The effect of renal arterio- and phlebography on the function of the renin angiotensin and hypophyseal-adrenal systems]. AB - Based on the analysis of a RX-ray study and a selective blood test for the activity of the plasma renin, aldesterone, hydrocortisone and adrenocorticotropic hormone (ACTH) in 57 patients with arterial hypertension--14 persons without renal failure, 14 ones regularly treated by hemodialysis, 29 patients with left orthostatic varicocele--the authors demonstrated the impact of the renal arterio- and phlebography on the hormone levels studied. Arteriography resulted in an increase in the absolute value of the renal vein renin mean 2.1-fold, aldosterone, 3.3-fold and hydrocortisone, 1.7-fold. A 2.2-fold increase in the renin activity and a 2.6-fold increase in the levels of aldosterone and hydrocortisone noted in all the patients were the result of retrograde renal phlebography. No correlations were established between the changes in hormone levels and the central mechanism of the secretion regulation (ACTH). Radiopaque investigations of the patients with arterial hypertension gave 22 per cent of false positive results with regard to the site of renin secretion and 18 per cent of those with regard to the participation of the studied kidney in renin secretion. The authors supposed a possible regulation of adrenal mineralocorticoid performance by a retrograde blood flow appeared through the adrenal central veins that was induced by phlebography--related elevation of blood pressure in the renal vein. PMID- 2186548 TI - [Ivan Ivanovich Makletsov]. PMID- 2186549 TI - [The surgical problem of coralliform nephrolithiasis]. PMID- 2186550 TI - [Trace element disorders as the etiology of kidney diseases]. PMID- 2186551 TI - Treatment of metastatic renal cell carcinoma with autolymphocyte therapy. Low toxicity outpatient approach to adoptive immunotherapy without use of in vivo interleukin-2. AB - Thirty-six patients with Stage IV renal cell carcinoma were treated with autolymphocyte therapy (ALT). This new form of adoptive immunotherapy is based on the infusion of relatively small numbers of autologous lymphocytes that are depleted of suppressor cells and immunized in vitro by a method designed for antigen-specific activation using a 3M KCl extract of autologous tumor and an autologous lymphokine mixture. Patients received six monthly infusions of immunized lymphocytes, all on an outpatient basis. The majority of patients experienced no toxicity. The few reactions that occurred were minor and self limiting; none required any medical intervention or subsequent delay in therapy. Patients also received oral cimetidine to reduce in vivo suppressor cell function. Survival at twenty-four months is 36 percent. Median survival is fifteen months, a significant improvement over the natural history of this disease. A multi-site, randomized, controlled trial of ALT in renal cell carcinoma has been initiated to confirm that this treatment causes a significant prolongation of survival with virtually no toxicity in these patients. PMID- 2186552 TI - Electron microscopic study of acute retrograde pyelonephritis in mice. AB - A strain of Escherichia coli O6:H-, which was isolated from a patient with acute pyelonephritis, was used to produce ascending pyelonephritis in mice. The histologic features at the early stage of acute pyelonephritis and the pathways of bacterial invasion and distribution in the infected kidneys were studied by using transmission electron microscope. The histologic changes were characterized by degeneration and destruction of renal pelvic and tubular epithelial cells, and a massive infiltration of polymorphonuclear leukocytes. Bacteria invaded the pelvic surface and spread over the renal medulla and cortex by contiguity twelve hours after infection. It was also shown that bacteria ascended the tubules, multiplied in the tubular lumina, destroyed the tubular epithelial cells, and spread over the renal cortex by twelve hours. In addition, bacteria and leukocytes phagocytizing bacteria were present in the capillaries in the renal interstitium twelve hours after infection. PMID- 2186553 TI - Natural history of fetal and neonatal hydronephrosis. AB - Since pyelocalicectasis alone is common in fetuses, we reviewed reports of fetal hydronephrosis that resolved spontaneously or at birth. Severe fetal hydronephrosis with calicectasis or parenchymal thinning rarely resolves spontaneously before or after birth. We also reviewed the clinical and experimental literature on renal hypertrophy. After unilateral nephrectomy in neonatal animals or after birth with congenital absence of one kidney in humans, the remaining kidney hypertrophies very quickly. In infants and young animals, the eventual size of the remaining kidney is inversely proportional to the age at which one kidney is lost. This improvement in residual renal function seen after renal loss in infancy, compared with older children, itself constitutes a strong argument for early relief of obstruction. If contralateral renal hypertrophy has occurred, the treated damaged kidney may resume growth in parallel with its hypertrophied mate but does not become as large or recover normal potential for growth. In other words, if correction of a unilateral obstruction is deferred until contralateral hypertrophy occurs, the obstructed kidney then has less potential for recovery of function. PMID- 2186554 TI - Fournier's gangrene in children. AB - Necrotizing fasciitis of the genitalia is a rare urologic emergency that is especially uncommon in children. We report a case of Fournier's gangrene in a four-year-old boy and analyze the data from 55 previously reported cases. Pediatric cases have been successfully managed with a more conservative surgical approach and have had a significantly lower mortality rate than adult cases. PMID- 2186555 TI - Genitourinary involvement of systemic sarcoidosis confined to testicle. AB - We report on a patient with systemic sarcoidosis who presented with a lesion of the genitourinary tract confined to the testicle. Clinically evident sarcoidosis of the testicle has been identified in few instances. Several recommendations in evaluating such lesions have been offered. A consensus on treatment is not yet defined. The therapeutic options are presented and the literature is reviewed. PMID- 2186556 TI - Simulator for transrectal ultrasound of prostate. PMID- 2186557 TI - The life and times of Alexander von Lichtenberg. PMID- 2186558 TI - [Extrinsic-allergic asthma--principles, diagnosis, therapy, danger of disability]. AB - In Germany approximately 5 per cent of the population suffer from asthma. The disease is characterized by nonspecific airway hyperresponsiveness to various stimuli, leading to airways obstruction. In the majority of cases sensitizations to inhaled or food allergens are revealed by skin tests and/or in-vitro tests (RAST) ("extrinsic" asthma). Due to an allergen-induced increase of non-specific airway hyperresponsiveness allergencontacts favor asthmatic symptoms after non specific stimuli, such as cold air or exercise. Therefore diagnostic measures in asthma should include allergic history and standard allergen skin tests in each case. Nonspecific stimuli often play a predominant role among the causes of acute airways obstruction, depending on the degree of nonspecific hyperresponsiveness. Other cases of asthma are characterized by the absence of senzitizations ("intrinsic" asthma). Usually, the symptomatology of these cases is more severe than in extrinsic asthma. In most cases of allergic asthma prognosis is favourable, in contrast to chronic obstructive bronchitis and/or emphysema. The therapeutic approach consists of allergen avoidance and hyposensitization, if feasible, and of a combination of bronchodilating and antiinflammatory drugs. A number of work places has to be avoided. Drug treatment should aim at reducing airways hyperresponsiveness and absence of asthmatic symptoms, requiring (inhaled) steroids in most cases. Other therapeutic principles have to be considered, such as allergen avoidance, cessation of cigarette smoking, change of work place, choice of favourable climates during holidays, and hyposensitisation. PMID- 2186559 TI - [Life expectancy and disability following pleural empyema]. AB - The pleural empyema, e.g. postpneumonial or postoperative, has, in an acute state of being, to be treated before all by an aimed intensive puncture, irrigation, and drainage therapy. Removing the cause of the empyema you can expect a cure as a rule, but in certain cases an operative intervention is still necessary. The chronic empyema often needs a decortication for an operative correction. The trials of medical treatment being often conservative and the chronic intoxication most often cause a strong impairment of the general condition. A lot of other organic affections or damages reduce the chances of cure and increase lethality. The chronic empyema not available for an operative correction has, as a whole, a bad long-term prognosis with a high morbidality and lethality. The qualities of living of these patients are often reduced a lot. PMID- 2186560 TI - [Clinical aspects, prognosis and therapy of liver cirrhosis]. AB - Hepatic cirrhosis is regarded as the terminal stage of the most diverse chronic liver diseases. It is characterized by nodular restructuring of the hepatic parenchyma which is accompanied by scar formation and transformation of the vascular system. The originally diseased liver becomes increasingly less prominent in pathophysiological terms, whereas the consecutive portocaval collateral circulation becomes increasingly effective. This leads to the serious complications of cirrhosis and finally also to death. The diverse influences of the disturbed individual functions of the liver on the body characterize the clinical picture with its multifarious symptoms and great variations in the alterations of clinical test values. An exact diagnosis (in the form of an early diagnosis) and clarification of the respective etiopathogenesis are of crucial significance for prognosis and therapy. Meticulous instruction and monitoring of the cirrhosis patient is absolutely necessary in practice. In this way, and also by means of a program of prophylactic measures, complications can be largely avoided. Today, treatment of the liver cirrhosis constitutes specific polypragmasy. However, it has produced an appreciable improvement in the quality of life and the life expectancy. PMID- 2186561 TI - [Prognosis following liver transplantation]. AB - Many aspects of liver transplantation need further developments, but in general liver transplantation has come out of the experimental state. Improved immunosuppressive drugs and better defined treatment protocols have had an important impact on the widespread growth of liver transplantation. However, survival after liver transplantation still depends on two distinct factors, the underlying disease leading to transplantation and the stage of the disease. Patients should be referred to transplantation earlier, in order to improve their survival probability. PMID- 2186562 TI - [Problems of the elderly, insulin injecting diabetic patients in ambulatory care]. AB - Not announced visits with interviews and practical demonstrations in the homes of 106 insulin-treated diabetics above 60 years of age produced rather sad results. Less than half of these patients were able to inject themselves. With increasing age insulin dosage was less and less correct; two thirds of the patients older than 75 years injected wrong doses. If the injections were performed by medical staff of the "Sozialstation", every second patient received his morning dosage only after breakfast or without any perceivable time-schedule. Only 7.5% of the patients seen followed their prescribed diet strictly, but 51+?% of them applied one or more "alternative" cures. It is true that in these older diabetic patients metabolic control does not play the same decisive role quoad vitam and concerning late complications as in younger ones, but the results we obtained should motivate us to improve, simplify and intensify patient education in the hospital and perform more controls of the lessons taught (and learned?) in the doctor's office. PMID- 2186563 TI - Parenteral amoxycillin/clavulanate in the treatment of diarrhoea in young pigs. PMID- 2186564 TI - Further studies on rabies virus isolated from healthy dogs in Nigeria. AB - Rabies viruses isolated from healthy dogs, were passaged in mice and adapted to cell culture. After 5-7 passages, isolated viruses were subjected to monoclonal antibody (Mab) characterization with a panel of 36 anti-nucleocapsid (NC) and 40 anti-glycoprotein (G) MAbs. The four viruses showed positive fluorescence with all NC hybridomas except MAb 422-5, confirming them as true rabies virus isolates. The anti-G MAb reactivity pattern was the same in the four isolates indicating that they belong to the same antigenic group, but were antigenically distinct from the Flury LEP rabies vaccine virus which is widely used throughout Nigeria for canine vaccination, and from other previously characterized street lyssaviruses from Nigeria. PMID- 2186565 TI - Monoclonal antibodies to Chlamydia psittaci guinea pig inclusion conjunctivitis (GPIC) strain. AB - Monoclonal antibodies to a strain of Chlamydia psittaci isolated from guinea pig inclusion conjunctivitis (GPIC) were developed. Only five of the 15 hybridomas isolated produced antibodies specific for the GPIC strain, while seven others produced antibodies which cross reacted with other strains and another species. Strain-specific and species-specific monoclonal antibodies were isotyped as IgG2a and IgG3, respectively. It appears that the GPIC strain has at least two epitopes, one of which is specific for the strain and the other common to the species. These monoclonal reagents may be used to immunotype GPIC agents, better than available methods and may be of potential use in the development of vaccines against chlamydial infections. PMID- 2186566 TI - Possession of identical nonconjugative plasmids by different isolates of Pasteurella multocida does not imply clonality. AB - Experiments were performed to test the hypothesis that possession of the same nonconjugative R plasmid by different isolates of Pasteurella multocida implied that they were of the same clone. Seven isolates of P. multocida were studied, two possessed an identical nonconjugative R plasmid (pVM109), four possessed another (pVM110), and one isolate possessed a nonconjugative R plasmid related to pVM110. Phenotypic and genotypic characteristics of the isolates were determined and compared. Isolates possessing the same nonconjugative R plasmid were shown to be different, and isolates possessing a different nonconjugative R plasmid were shown to be the same. We conclude that possession of an identical nonconjugative R plasmid by two isolates of P. multocida does not imply clonality. PMID- 2186567 TI - Bovine natural cell mediated cytotoxicity (NCMC): activation by cytokines. AB - Incubation of bovine peripheral blood mononuclear leukocytes (PBML) with the cytokines (CK) IL-2, alpha-IFN, gamma-IFN or IL-4 resulted in significant increases in natural cell mediated cytotoxicity (NCMC) over endogenous levels, as determined in an 18 h 51Cr-release assay using the human K562 or mouse Yac-1 target cell lines. Endogenous cytotoxic activity of bovine natural effector cells (NEC) using K562 or Yac-1 target cells was minimal (killing less than 8%). After 18 h of incubation with the CK hurIL-2, alpha-bovrIFN, gamma-bovrIFN or hurIL-4, NEC had significant increases in cytotoxic activity for both K562 and Yac-1 target cells. Significant increases in cytotoxic activity were not found after incubation of NEC with IL-1 or beta-IFN. Specific killing varied with CK concentration in a dose dependent manner and was proportional to effector:target cell ratio. Activation of the bovine NEC by CK was rapid, occurring within 6-12 h of incubation with alpha-IFN or gamma-IFN and within 12-18 h of incubation with IL-2. Incubation of bovine PBML with IL-2 and alpha- or gamma-IFN or with alpha IFN and gamma-IFN showed that these CK do not act in a synergistic manner to increase NCMC in the bovine NEC. PMID- 2186568 TI - The use of monoclonal antibodies in an enzyme immunospot assay to detect isotype specific antibody-secreting cells in pigs and chickens. AB - Monoclonal antibodies directed against porcine immunoglobulin isotypes G, G1, G2, M, and A and against chicken immunoglobulin isotopes G, M, and A were tested in an antigen-specific spot-forming cell (SFC) assay based on the principle of the enzyme immunoassay. The SFC assay was used to quantitate ovalbumin (OA)-specific antibody-secreting cells (ASC) in pigs that had been primed and boosted with OA. The SFC assay was also used to quantitate trinitrophenyl (TNP)-specific ASC in chickens that had been primed with TNP-conjugated keyhole lympet haemocyanin (TNP KLH). Although, the classical plaque-forming cell (PFC) assay cannot reliably detect isotope-specific ASC in pigs and chickens, it can detect these cells in mice. Therefore, we compared the OA- and TNP-specific SFC assays with PFC assays that were specific for these antigens in mice. The study demonstrated that the SFC assay is superior to the PFC assay in detecting both OA-specific ASC and TNP specific ASC. The frequencies of OA-specific and TNP-specific SFC detected in mice were of the same order of magnitude as those detected in pigs and chickens. We concluded that the SFC assay is the better method for quantitating ASC in pigs, chickens, and probably all domestic animals for which isotype-specific monoclonal antibodies are available. PMID- 2186569 TI - [Comparison of the effects of depot isosorbide dinitrate (Isoket Retard 120) and diltiazem in patients with exertional angina pectoris]. AB - In a simple blind crossover 7-week study with a randomized beginning the authors compared in 13 patients with stable angina pectoris after exercise the action of diltiazem (Blocalcin 60, Lachema) and isosorbidedi nitrate (Isoket retard 120, Schwarz). Both drugs improved significantly, as compared with placebo, the tolerance of the load, reduced the frequency of stenocardias per 24 hours, diltiazem also the nitroglycerin consumption per 24 hours. Diltiazem reduced significantly, as compared with isosorbidedi nitrate, the pulse rate at rest, it reduced significantly Robinson's index and the diastolic pressure at rest. In none of the other investigated parameters there was a significant difference between the two drugs and both are valuable in the treatment of angina after exercise. Diltiazem was well tolerated by the patients, while headache was a frequent side-effect of isosorbide dinitrate. PMID- 2186570 TI - [Manifestations of dysfunction of the proximal tubules after intravenous urography]. AB - The aim of the work was to investigate functional changes of tubular cells after i.v. urography. As evidence the authors used assessment of urinary levels of membrane-bound enzymes--alkaline phosphatase (AP), gamma-glutamyl-transpeptidase, lysosomally bound enzymes N-acetyl-beta-D-glucosaminidase and its isoenzyme B and the low molecular protein, beta-2-microglobulin. The above substance were assessed in 15 patients with different nephropathies where i.v. urography was indicated. The examinations were made in 24-hour urine samples before i.v. urography and in two 24-hour samples after administration of the contrast substance. In all patients a significant rise of tubular enzyme excretion was observated as well as of beta-2-microglobulin. The greatest rise was recorded in alkaline phosphatase in the second sample after administration of the contrast substance (432% of the initial value). Beta-2-microglobulin and N-acetyl-D glucoseaminidase rose already during the first collection period (B2M to 357% and NAG to 181% of the initial values). The authors conclude that i.v. urography made by hyperosmolar iodinated preparations (Verografin, Iodamide) significantly affects the function and integrity of the proximal tubule. The applied spectrum of examinations is suitable also for further investigations of the effect of contrast substances on cells of the proximal renal tubule. PMID- 2186571 TI - [Variations in indicators of humoral immunity in type I diabetes]. AB - The authors examined 21 patients with type I diabetes within 30 days after establishment of the diagnosis and during the first year of the disease. In 17 they detected autoantibodies against insulin at the time of assessment of the diagnosis before administration of the therapeutic insulin preparation. Fourteen patients had antibodies against the surface of islet cells (ICSA), the titre of which declined during the first year of the disease. The serum immunoglobulin level (IgG, IgM and IgA) was on average within the normal range; however, in two patients at the time of establishment of the diagnosis and in three patients after one month IgG was above normal, in eight patients the IgM level was at the time of establishment of the diagnosis above normal, one month later this was the case only in two patients and in four patients the IgA level was permanently low. During the investigation period the level of C-3 and C-4 components of the complement declined steadily and the level of circulating immune complexes increased. The mentioned deviations were not associated with the concurrent infectious disease at the time of establishment of the diagnosis or with metabolic indicators. The patients were treated the whole time by an intensified insulin regime--principle basal bolus or continuous subcutaneous infusion of single component insulin. PMID- 2186572 TI - [Endocrine diseases in pregnancy]. PMID- 2186573 TI - [Treatment of hypertension in pregnancy--verified, questionable and controversial treatment]. PMID- 2186574 TI - [Acute abdomen--interdisciplinary aspects]. PMID- 2186575 TI - [Traumatology and pregnancy]. PMID- 2186576 TI - [The history of toxicology of the "Haber's Constant"]. AB - The "Haber's Constant", the product of concentration (in ppm) and time (in minutes) to cause death, was mainly used in connection with the development of chemical warfare agents during World War I. But up to now the Haber's Constant is important to compare toxic gases tested on many different species of animals in research and development as well as in hygiene practice. The very first experiments in this field were done long before Haber's work in 1900 by Ernest Warren (London). PMID- 2186577 TI - [Current status of the knowledge about benzene effect--metabolism]. AB - This is a review about the results of the last years concerning the explanation of the benzene metabolism. Benzene induces some enzymes necessary for its own biotransformation. The different enzymes in liver and bone marrow elucidate the preference of the toxic activity on the hemopoietic system. PMID- 2186578 TI - [Current status of knowledge of the effect of benzene. Impairment of blood and hemopoiesis]. AB - The alteration of the hemopoiesis is the result of a lot of particular cases. The inhibition of the microtubuli assembly suppresses the cell division because of the missing of the spindle formation. This is associated with an inhibition of the supporting stroma of the bone marrow and of the different lymphocytes complicated with a depression of colony stimulating factors. There is also an alkylation of the nuclear and mitochondrial RNA, DNA and proteins together with an inactivation of the DNA polymerase. Immunosuppressive effects are associated with autoimmune events. Benzene is classified as a weak carcinogenic initiator. PMID- 2186579 TI - [Effect of vasodilator agents on the character and incidence of cardiac arrhythmia in chronic heart failure]. AB - In 50 patients with chronic congestive heart failure (CCHF, III or IV class), aged 62.8 +/- 9.1 years, who were treated with digoxin (Dx) and furosemide (F) (investigation A), continuous 24-hour ecg registration was performed according to Holter. Next, this treatment was extended by two-week administration of nifedipine (N) or isosorbide dinitrate (S) (investigation B), followed by one month addition of captopril (Cp) (investigation C). During the last two weeks Dx, F, N or Dx, F, S were administered with Cp being withdrawn (investigation D). At the end of each stage of the treatment ecg registration was repeated according to Holter. At the same time, during the investigation A there were performed determinations of blood serum sodium, potassium and digoxin concentrations, two dimensional echocardiography and evaluation of submaximal exercise tolerance. In 96 per cent of patients with CCHF, treated with Dx and F, cardiac rhythm disturbances were found. In 53.3 per cent life-threatening ventricular arrhythmias occurred, including unstable ventricular tachycardia in 11.1 per cent of patients. Addition of N or S to the classical treatment did not decrease either patient number or amounts of cardiac rhythm disturbances in individual classes according to Lown. Also Cp did not affect numbers of patients with cardiac rhythm disturbances, but it decreased numbers of patients with life threatening ventricular arrhythmias from 53.3 per cent to 28.9 per cent (from 24/45 to 13/45). At the same time, Cp significantly decreased numbers of ventricular arrhythmias in class 3 and 4a (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186580 TI - [Halle physicians as witnesses of the times and specialty chronologists. V. From the memoir literature of 7 decades (1848-1918)]. AB - The development of medicine at the German universities in the years between 1848 and 1918 is reflected by a series of autobiographical representations. Despite all their pride in the top position obtained for the time being critical authors not in the least lock up their insight concerning certain faulty developments. Already in the first decenniums of the 20th century most German universities and colleges are deprived of the bloom of preceding decades. At the instance of Halle particularly gross effects are shown. PMID- 2186581 TI - Analysis of variables of plasmid transformation of a bacterial vaccine: studies on recombinant BCG. AB - Stepwise regression analysis was applied to evaluate the strength order of the effect of five explanatory variables on the transformation of BCG substrains by electroporation with hybrid shuttle plasmid [pAL5000:pIJ666] and derived as YUB plasmids containing a kanamycin resistance selection marker. From 66 successful transformations, data of 42 transformations of the Pasteur 1172P2 BCG substrain are analysed. The estimated parameters in the multiple linear regression model show that the association of the explanatory variables with the explained variable, i.e. the efficiency of the transformation of BCG expressed in c.f.u./microgram DNA, in decreasing strength order is: concentration of the plasmid DNA; viability of the non-electroporated concentrated BCG suspensions; viability of the BCG cultures; age of the BCG cultures; and time constant of the electroporation. More extended analysis of other factors of the transformation will improve objective statistical inference regarding the biophysical and molecular biological interpretation of the transformation mechanism by electroporation of the different bacterial species. More precise understanding of optimal conditions of genetic transformation will be particularly important for developing recombinant BCG vaccines. PMID- 2186582 TI - Protection of adult rabbits and monkeys from lethal shigellosis by oral immunization with a thymine-requiring and temperature-sensitive mutant of Shigella flexneri Y. AB - As an approach to the development of attenuated strains, thymine-requiring (Thy-) and temperature-sensitive (Ts-) single and double mutants of Shigella flexneri Y have been isolated by u.v. mutagenesis and selection. The mutants retained the 140 MDa plasmid, were Sereny-negative and avirulent in 'conditioned' rabbits and in monkeys. Rabbits and monkeys immunized orally with two doses of the mutants were solidly protected against disease and lethality when challenged with the homologous virulent strain. The immunized animals had higher levels of antibodies reactive to the lipopolysaccharide of the wild type strain and also a shorter duration of shedding of the challenge bacteria. It was concluded that Thy- and Ts mutants of Shigella spp. are highly attenuated and immunogenic to be considered for further studies towards the development of vaccine candidates. PMID- 2186583 TI - [Genetic aspects of early spontaneous abortion]. AB - Spontaneous abortions are the most frequent complications in pregnancy. Especially in early pregnancy abortions are often genetically caused. The most important role between chromosomal disorders play the Trisomy, Triploidy and X0 Monosomy. Against the background of more recent findings the frequency, origins of several genetic disorders and the morphological expression in placental tissue are discussed in this review. The chromosomal situation of hydatidiform and partial mole as well as the question for the causes of malignancy-tendence of complete moles from genetic view are also considered. The importance of the knowledge of genetic disorders to correlate the microscopic placental findings and the karyotype and to support medical consultation is referred, too. PMID- 2186584 TI - [Detection of Actinomyces on an IUD--consequences?]. AB - Smears from 210 removed IUD's were taken in order to investigate them on actinomycetes. In 20 cases (9.5%) agglomeration of filaments and spores of actinomyces were found. All patients were free of complaints. During the control curettage carried out later on only in one of the cases actinomyces were found in the endometrium. Signs of serious inflammation couldn't be proved. In cases without any complaints no clinical consequences are to be followed after having found actinomyces on the removed IUD. PMID- 2186585 TI - [Labor induction, how?]. PMID- 2186586 TI - Current state of treatment of carcinoma of the oesophagus and gastro-oesophageal junction. Clinical review. PMID- 2186587 TI - Prophylactic single-dose fosfomycin and metronidazole compared with neomycin, bacitracin, metronidazole and ampicillin in elective colorectal operations. AB - Two antibiotic regimens for the prophylaxis of infection after colorectal operations were compared in a prospective, double blind, randomised controlled trial in 244 patients. Ninety-five patients (39%) were either excluded before randomisation or withdrawn, leaving 149 for analysis. Group 1 (n = 72) received a single infusion of 8 g fosfomycin and 1 g metronidazole at the induction of anaesthesia. Group 2 (n = 77) received bacitracin 250 mg plus neomycin 250 mg (as four tablets on three occasions over two days), metronidazole 500 mg tablets three times a day for one day, and ampicillin 1 g intravenously at induction of anaesthesia. Nine patients in group 1 (13%), 95% confidence interval (CI) 6.9 to 22.4, developed infective complications, compared with 8 in group 2 (10%), 95% CI 4.6 to 19.4. The overall infection rate was 17 of 149 evaluable patients (11%), 95% CI 6.8 to 17.7. Seven patients died (five in group 1 and 2 in group 2), two of whom (one in each group) died as a direct result of infective complications. Long operations and obesity were the most important risk factors, and may indicate a need for longer prophylaxis. Fosfomycin, which is mainly active against aerobic bacteria, was both safe and useful when combined with metronidazole. PMID- 2186588 TI - Effect of acute administration of metoclopramide on insulin secretion in man. AB - The effect of acute i.v. administration of 2.5 mg metoclopramide (MCP), an antidopaminergic agent with low serotoninergic activity, on blood insulin and glucose concentrations was studied in 9 healthy men. MCP was able to significantly decrease basal serum insulin levels (from 6.8 +/- 1.1 to 4.3 +/- 0.7 microU/ml in 120 min; p less than 0.025) with a parallel elevation in blood glucose (from 72.5 +/- 1.1 to 82.6 +/- 2.5 mg/dl in 120 min; p less than 0.01). These findings, which were not observed after placebo, and appeared not to be explained by the spontaneous occurrence of physiological oscillations of insulin and glucose plasma levels, are consistent with similar effects observed after administration of other antidopaminergic agents and with the stimulatory activity on insulin and glucagon release described during dopamine infusion in man. PMID- 2186590 TI - Acta Orthopaedica Scandinavica. Sixtieth anniversary. PMID- 2186589 TI - Obesity and diabetes. AB - The factors which are involved in the development of diabetes and obesity have been reviewed. These include the age of the individual, the duration and magnitude of the obesity, whether there is a family history of diabetes mellitus, the regional distribution of body fat, and the function of the pancreatic islet. These factors help in understanding the reasons why obesity poses such a high risk for developing diabetes mellitus. PMID- 2186591 TI - Lower thrombosis risk with epidural blockade in knee arthroplasty. AB - Thirty-six patients scheduled for knee arthroplasty were randomized to general or epidural anesthesia that was prolonged into the postoperative period. All the patients wore graded compression stockings until full ambulation. No other thrombo-prophylactic treatment was given. In diagnosing deep venous thrombosis, bilateral ascending venography was performed 9-11 days after surgery. The incidence of thrombosis was 2/13 in the epidural group versus 10/16 in the general anesthesia group (P less than 0.05). PMID- 2186592 TI - Secondary repair of ulnar nerve injury. 44 cases followed for 2 years. AB - A series of 44 patients with complete section of the ulnar nerve was reviewed on average 2 years after secondary repair. The procedures applied were fascicular grafting in 33 cases, epineural suture in 7, and suture in 4. Useful ulnar motor function was restored in 22 cases of fascicular grafting, in all 4 of fascicular suture and in 3 of epineural suture. Sensibility recovered in 23 patients operated on by fascicular grafts and in 10 of 11 treated by epineural or fascicular suture. Cases with unsatisfactory results had other associated severe lesions, i.e., median nerve section, vascular damage or tendon injuries. Early repair of clean-cut nerve sections by fascicular or epineural suture gives a good chance for recovery. Grafting should be performed within 3 months and no later than 1 year after the injury. PMID- 2186593 TI - Vibration arthrometry. A preview. AB - Throughout the ages, physicians have listened to sounds and felt vibrations from human joints in their attempts to diagnose pathology. They have used a wide vocabulary to describe these phenomena, but technology has been slow to provide recording and analytic equipment. Lately, accelerometers have been used with considerable success in a new noninvasive method now known as vibration arthrometry (formerly "arthrography"). The technique has been used in early detection of congenital dislocation of the hip and also in diagnosis of meniscal pathology. More recently, patellar vibration has been used to assess the mechanical properties of articular cartilage. Vibration arthrometry has also yielded new information on a possible damage mechanism associated with shock vibration that arises during cavitation of synovial fluid. Joint vibrations are therefore useful aids to diagnosis and may even be etiologic in orthopedic disease. PMID- 2186594 TI - A case of occipitocervical fusion in myeloma. AB - Posterior fusion (from occiput to C4) with an iliac graft on the right side and methyl methacrylate on the left side was performed in a 49-year-old woman with an osteolytic destruction of the second vertebral body caused by multiple myeloma. Thirty months after the fusion, the patient remains free from pain, although there is progression of the osteolytic lesion, now extending to the third vertebral body. PMID- 2186596 TI - Polycystic ovarian disease: a challenge and controversy. PMID- 2186595 TI - High levels of circulating met-enkephalin in pregnant and menstruating type 1 diabetic women. AB - Plasma met-enkephalin (MET-ENK) levels are increased in type 1 diabetic women and in pregnant diabetic women in comparison with normal women. Plasma MET-ENK levels further increase in the peripartum period both in diabetic and non-diabetic females, probably due to the analgesic and behavioural properties of the opioid system. PMID- 2186597 TI - Bioluminescence and chemiluminescence literature--Lux, Luc and Phot genes. AB - This is the first of a series of special compilations of references devoted to a particular topic in luminescence. References are numbered sequentially, except when a reference has appeared in a previous Bioluminescence and Chemiluminescence Literature section in which case it retains the original number. PMID- 2186598 TI - Novel monomeric luciferase enzymes as tools to study plant gene regulation in vivo. AB - Taking advantage of a specially constructed vector, luciferase LuxA and LuxB subunits were connected in frame to different amino acid linkers to reproduce a series of monomeric luciferase enzymes. A comparison of their activities in E. coli cells demonstrated that the length of the linkers positively affected activity. One luciferase fusion gene was expressed in plant cells, and we showed that this gene activity could be monitored directly without destructive sampling. PMID- 2186599 TI - Control of the lux regulon of Vibrio fischeri. AB - Regulation of expression of bioluminescence from the Vibrio fischeri lux regulon in Escherichia coli is a consequence of a unique form of positive feedback superimposed on a poorly defined cis-acting repression mechanism. The lux regulon consists of two divergently transcribed operons. The leftward operon contains only a single gene, luxR, which encodes a transcriptional activator protein. The rightward operon contains luxI, which together with luxR and the 218 base pairs separating the two operons comprises the primary regulatory circuit, and the five structural genes, luxC, luxD, luxA, luxB and luxE, which are required for the bioluminescence activity. Transcription of luxR from PL is stimulated by binding of the E. coli crp gene product to the sequence TGTGACAAAAATCCAA upstream of the presumed promoter. Binding of pure E. coli CAP protein in a cAMP-dependent reaction to the V. fischeri lux regulatory region has been demonstrated by in vitro footprinting. The luxI gene product is an enzyme which catalyses a condensation reaction of cytoplasmic substrates to yield the autoinducer, N-(3 oxo-hexanoyl) homoserine lactone. Accumulation of autoinducer, which is freely diffusible, results in formation of a complex with LuxR. The complex binds to the sequence ACCTGTAGGATCGTACAGGT upstream of PR to stimulate transcription of the rightward operon. Increased transcription from PR should yield increased levels of LuxI and higher levels of autoinducer which would further activate LuxR. The LuxR binding site is also a LexA binding site, as demonstrated by in vitro footprinting. Basal transcription from both PL and PR is repressed by sequences within the luxR coding region.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186600 TI - Stereotactic craniotomy and intraoperative lesion localisation using the Brown Robert-Wells frame. Technical note. AB - A simple technique of stereotactic craniotomy and intraoperative lesion localisation that uses the Brown-Robert-Wells (BRW) stereotactic frame is presented. The method optimises craniotomy placement and facilitates localisation of small intracerebral lesions. Using the system, 16 patients have had resection of intracranial neoplasms from deep and/or eloquent areas of the brain with no neurological morbidity. PMID- 2186602 TI - Neurological complications in HIV infection. Personal experience. AB - The personal experience on neurological disturbances associated with early HIV infection and AIDS is reported. Central nervous system (CNS) involvement occurred during the early stages in 3 cases: 2 patients with HIV-seroconversion (CDC category III) and one patient with persistent generalized lymphadenopathy (PGL, III group CDC, 1986). The patients had HIV acute meningitis. The neurological manifestations in AIDS had high incidence (49 of 83 cases), often with multiple aetiology in single patients. We remark the necessity of an early aetiological diagnosis to address the treatment. PMID- 2186601 TI - Continuous recording of middle cerebral artery blood velocity in clinical neurosurgery. AB - Intracranial pressure, arterial blood pressure, and middle cerebral artery blood velocity were monitored for periods from 1 to 10 days in 30 neurosurgical intensive care patients. The recordings revealed rapid changes in the cerebral perfusion and gave insight into individual cerebral haemodynamic states. Twenty patients consistently showed CO2 reactivity within normal limits, between 2.5 and 5% per mm Hg (19-38% per kPa). Severely impaired CO2 reactivity, considerably below 1% per mm Hg (7.5% per kPa) was observed in four patients. Three of these patients died, while the fourth patient survived in a persistent vegetative state. Seven patients demonstrated pressure-passive blood velocity changes throughout the observed CPP range. The four patients with severely impaired CO2 reactivity all belonged to this group. The recordings from three of the remaining 23 patients showed signs of MCA blood velocity autoregulation with a lower regulatory limit of about 40-45 mm Hg. This observation is in keeping with findings from electromagnetic flowmetry on brain arteries in the neurosurgical operating field, and supports blood velocity measurements as a relevant index of brain perfusion in clinical neurosurgery and neuro-intensive care settings. PMID- 2186603 TI - Study of beta-2 microglobulin and neopterin in serum and cerebrospinal fluid of HIV-infected patients. PMID- 2186604 TI - Macrophage-derived cytokines in the cerebrospinal fluid of HIV-1-infected patients. PMID- 2186605 TI - Acute reduction of atrial overload during vasodilator and diuretic therapy in advanced congestive heart failure. AB - Although acute afterload reduction is known to improve cardiac output in patients with congestive heart failure (CHF), the effect of therapy on the atrial overload directly causing congestive symptoms has not been systematically studied. Atrial volumes and mitral and tricuspid regurgitation, in addition to left ventricular ejection fraction and indexes of left ventricular contractility (mean acceleration, ejection time and peak systolic pressure/end-systolic volume index), were measured using 2-dimensional and Doppler echocardiography and color flow imaging in 30 patients with advanced CHF, before and after acute vasodilator and diuretic therapy tailored to hemodynamic goals. Therapy increased stroke volume by 64% (36 +/- 10 to 55 +/- 14 cc), decreased right atrial pressure by 45% (15 +/- 5 to 8 +/- 4 mm Hg), systemic vascular resistance by 36% (1,700 +/- 400 to 1,030 +/- 300 dynes s cm-5) and pulmonary capillary wedge pressure by 37% (31 +/- 6 to 19 +/- 6 mm Hg) (all p less than 0.001). Echocardiography showed simultaneous reductions in left and right atrial volumes: 24 +/- 19 and 18 +/- 12%, respectively (p less than 0.001). Mitral and tricuspid regurgitation measured by color flow fraction both decreased by a mean of 44% (p less than 0.001). While ejection fraction increased from 15 +/- 5 to 19 +/- 7% (p less than 0.001), there were no changes in relatively load-independent indexes of contractility. Therefore, acute therapy with vasodilators and diuretics in advanced CHF causes reductions in atrial volumes and atrioventricular valve regurgitation that are evident from serial noninvasive studies and may play a major role in the improvement of congestive symptoms. PMID- 2186606 TI - Comparison of effects of nitrendipine versus hydrochlorothiazide on left ventricular structure and function and neurohumoral status in systemic hypertension. PMID- 2186607 TI - Intravascular high frequency two-dimensional ultrasound detection of arterial dissection and intimal flaps. PMID- 2186608 TI - Detection of intraarterial thrombus by intravascular high frequency two dimensional ultrasound imaging in vitro and in vivo studies. PMID- 2186609 TI - Issues surrounding a local cardiac renin system and the beneficial actions of angiotensin-converting enzyme inhibitors in ischemic myocardium. AB - Several experimental in vitro and in vivo studies have shown that structurally diverse converting enzyme inhibitors improve contractile dysfunction, as well as reduce arrhythmia production and acute mortality after occlusion of the coronary artery. Biochemical data have demonstrated that some inhibitors of converting enzyme bind better to cardiac angiotensin-converting enzyme (ACE) than others; however, there has not been any demonstrated correlation between inhibition of the enzyme and improvement in cardiac physiology in the acutely dysfunctioning stunned myocardium. It is assumed that ACE inhibitors reduce tissue generation of angiotensin II; however, this relationship as well as peptide levels in coronary venous effluent need to be specifically measured. The multiple substrates of ACE necessitate further work to explore the role of bradykinin and prostacyclin, which have been implicated by some workers as contributing to the beneficial action of ACE inhibitors. A new question is whether sulfhydryl-containing ACE inhibitors are scavengers of toxic free radicals. Captopril, e.g., has been shown to be a free radical scavenger in superoxide-generating systems. Further work is required; however, as one report has recently shown, captopril does not directly scavenge superoxide but acts indirectly as an antioxidant or by altering the concentration of cytochrome c. PMID- 2186610 TI - Protection of the myocardium during myocardial infarction: pharmacologic protection during thrombolytic therapy. AB - The most effective way to protect injured myocardium during the early phases of evolving myocardial infarction is with reperfusion. However, reperfusion may induce further myocardial injury. Alterations in the major determinants of myocardial oxygen demand, including increases in heart rate, contractile state and myocardial wall tension may also increase infarct size. An understanding of the basic mechanisms involved in the evolution of myocardial injury during myocardial infarction is important to the development of protective strategies that may reduce infarct size or attenuate reperfusion-induced myocardial injury, or both. Selective calcium antagonists, beta blockers, and phospholipase antagonists or inhibitors may reduce infarct size in association with early reperfusion. Reperfusion injury may be attenuated by free radical scavengers and calcium antagonists. Reinfarction, after the initial event, may ultimately be reduced in frequency by pharmacologic strategies that interfere with platelet adhesion, aggregation, and mediator release from activated platelets and white cells that promote further platelet aggregation or induce coronary artery vasoconstriction. Included among protective strategies are thromboxane receptor antagonists and synthesis inhibitors, serotonin receptor antagonists, possibly leukotriene synthesis inhibitors or receptor antagonists, and aspirin. Future clinical trials should test the combined efficacy of reperfusion and selected pharmacologic strategies that alter calcium accumulation in the injured myocardium, diminish the injurious effects of beta- and alpha-adrenergic mechanisms and oxygen-derived free radicals on injured myocytes, and prevent reocclusion mediated by platelets and platelet mediators. PMID- 2186611 TI - Renal protective effects of angiotensin-converting enzyme inhibition. AB - Nephron loss is a common progression of a diverse range of kidney diseases. Recent experimental models of chronic renal disease have suggested that hemodynamic and nonhemodynamic mechanisms play key roles in progressive renal injury. Extensive renal ablation in the rat was followed by development of altered glomerular hemodynamics. Albuminuria and histologic damage leading to focal glomerulosclerosis were preceded by the development of increased glomerular pressures and were prevented by interventions such as severe dietary protein restriction and angiotensin-converting enzyme (ACE) inhibitor therapy. Both experimental interventions ameliorated glomerular hypertension. It was therefore concluded that these interventions ameliorated injury by glomerular hemodynamic effect. Similar findings were obtained in a rat model of type I diabetes mellitus induced by streptozotocin in which glomerular hemodynamic factors appeared important to the development of progressive renal disease. Recent studies have suggested that nonhemodynamic factors have important roles in the progression of glomerular injury. For example, although the predominant effects of ACE inhibitor therapy appear to be hemodynamically mediated, data are emerging which suggest that these agents may also influence growth/proliferation of glomerular cells. Because hyperplasia/hypertrophy may influence glomerular susceptibility to injury, this may also be a potential mechanism whereby ACE inhibitor therapy influences glomerular damage. In addition, a variety of studies have suggested that hyperlipidemia, which is frequent accompaniment of glomerular disease, is an important modulator of glomerular injury independent of glomerular hemodynamic effects. Coagulation factors, calcium phosphorus balance, as well as the genetic susceptibility of the glomerulus to injury, all appear to contribute to progressive nephron destruction. PMID- 2186612 TI - Hypnotherapy for traumatic grief: janetian and modern approaches integrated. AB - Traumatic grief occurs when psychological trauma obstructs mourning. Nosologically, it is related to pathological grief and posttraumatic stress disorder (PTSD). Therapeutic advances from both fields make it clear that the trauma per se must be accessed before mourning can proceed. The gamut of psychotherapies has been employed, but hypnosis appears to be the most specific. Pierre Janet provided a remarkably modern conceptual basis for diagnosis and treatment based on a dissociation model. His approach is combined with contemporary innovations to present a systematic and integrated account of hypnotherapy for traumatic grief. PMID- 2186613 TI - Hepatologic considerations in patients with parenchymal liver disease undergoing surgery. AB - Patients with liver disease requiring surgical procedures are at increased perioperative risk. In addition, the deleterious effect of anesthesia on hepatocellular function, altered drug pharmacokinetics, aberrant hemostasis, postoperative encephalopathy and infection, with multiorgan failure, all contribute to perioperative morbidity and mortality. Although limited by the lack of widely accepted quantitative liver function tests, preoperative evaluation and risk assessment is imperative. Acute viral hepatitis, alcoholic hepatitis, refractory coagulopathy, Child's class C cirrhosis, and emergent surgery are major risk factors predictive of a poor outcome. In addition, elective abdominal surgical procedures should be avoided in potential candidates for orthotopic liver transplantation. Identification and correction of reversible risk factors via meticulous preoperative definition of the etiology, chronicity, and severity of the patient's liver disease within the confines of surgical urgency is the goal of the preoperative hepatology consultation. PMID- 2186614 TI - Biliary lithotripsy: more questions than answers. The ACG Committee on FDA Related Matters. PMID- 2186615 TI - Nutritional fads. PMID- 2186616 TI - An investigation into the effects of oral iron supplementation on in vivo Hemoccult stool testing. AB - This prospective, randomized, double-blind, crossover study examined the effects of oral iron ingestion on fecal occult blood testing. One hundred healthy and asymptomatic volunteers collected stool samples after 2-wk courses of both oral iron (either ferrous sulfate or ferrous gluconate) and placebo, while following strict medicinal, dietary, and collection instructions. Each sample was tested by both the Hemoccult II and Hemoccult Sensa methods. Of the participants who completed this study (n = 78), there were no positive results for occult blood after iron ingestion when tested by either method. Only one participant displayed a positive result while taking the placebo, with this specimen considered contaminated by unexpected menses. From these findings, it can be concluded that oral iron supplementation does not cause false-positive results when the Hemoccult II or Hemoccult Sensa method is used for fecal occult blood testing. PMID- 2186617 TI - Congestive gastropathy and other upper endoscopic findings in 81 consecutive patients undergoing orthotopic liver transplantation. AB - Pretransplant endoscopic findings in 81 consecutive patients with nonalcoholic liver disease were examined to determine the spectrum of abnormalities encountered, with particular attention to mucosal changes consistent with congestive gastropathy. Abnormalities were observed in 75 patients (93%). Twenty three patients (28%) had findings suggestive of congestive gastropathy: petechiae, focal and diffuse intense erythema, with or without erosions, edematous mucosa with a fine white reticulated or mosaic pattern, and cherry red spots resembling vascular malformations. Congestive gastropathy was the second most common abnormality identified after esophageal varices (66 patients, 81%). Other abnormalities included gastric varices in 13 patients (16%), esophagitis in seven (9%), gastric ulcers in six (7%), duodenal ulcer in 11 (14%), postsclerotherapy esophageal ulceration in 10 (12%), and a postsclerotherapy symptomatic esophageal stricture in one. The prevalence of congestive gastropathy has provided a stimulus for our prospective evaluation of gastric mucosal disease before and after liver transplantation or portosystemic shunt. PMID- 2186618 TI - Chronic lymphocytic leukemia presenting with massive chylous ascites. AB - A newly diagnosed patient with chronic lymphocytic leukemia who presented with ascites is described. Paracentesis revealed the presence of massive chylous ascites. Further work-up disclosed leukemic infiltration of the liver and bone marrow. Complications leading to his death included renal failure, gastrointestinal hemorrhage, bacterial peritonitis, and Staphylococcus aureus bacteremia. Chylous ascites is a rarely reported manifestation of chronic lymphocytic leukemia. The case is presented, and a review of the literature is discussed. PMID- 2186619 TI - Prevention of recurrent variceal hemorrhage: to block or not to block? PMID- 2186620 TI - Meningococcus septicemia: a complication of endoscopic injection sclerotherapy. PMID- 2186621 TI - ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs. PMID- 2186622 TI - Update on safe handling of hazardous drugs: the advice of experts. AB - Questions related to the handling of hazardous drug products were discussed by a panel of pharmacy practitioners. The panel addressed the following issues: pharmacists' responsibilities for instructing patients, nurses, and physicians on safe handling of hazardous drug products; safe transport of hazardous drug products outside the hospital; disposal of hazardous drug products, items contaminated by these products, and body wastes of patients receiving these drugs; appropriate operation, venting, cleaning, decontamination, and recertification of biological safety cabinets (BSCs); the protective clothing and technique that should be used by workers in BSCs; monitoring the health of workers who handle hazardous drug products; pharmacy's potential liability for nonconformance to published guidelines; whether and how pharmacies that prepare few doses of hazardous drug products should comply with stringent guidelines geared to institutions that handle many doses of these products; and precautions for handling hazardous drug products for oral administration, caustic products, and vesicants. Safe limits for time and amount of exposure to hazardous drugs are unknown, but ASHP's revised Technical Assistance Bulletin on Handling Cytotoxic and Hazardous Drugs and current guidelines from the federal Occupational Health and Safety Administration provide guidance on precautions that should be observed. PMID- 2186623 TI - Double-blind randomized clinical trial of self-administered podofilox solution versus vehicle in the treatment of genital warts. AB - PURPOSE: Genital warts are a highly prevalent and chronic sexually transmitted disease for which there is no completely satisfactory therapy. Conventional ablative therapy requires repeated treatment, often for months or years. This study was undertaken to evaluate the safety and efficacy of 0.5% podofilox in patient-administered treatment of penile warts. PATIENTS AND METHODS: Thirty eight men with penile warts were randomly assigned to double-blind, self administration of 0.5% podofilox solution or placebo, twice daily for 3 days per week for 4 weeks. Eleven podofilox and 15 placebo recipients with residual warts then received an additional 4 weeks of open-label treatment. RESULTS: By the end of treatment, podofilox recipients had their mean wart number and area reduced to 15.9% and 5.1% of baseline values, compared to 97.4% and 92.9% in the placebo group (p = 0.0001). Local adverse reactions were more common in the podofilox group, but were transient. Complete disappearance of warts was observed in 25 (53.3%) of 45 treatment courses, including open-label treatment. Recurrences of warts after therapy were frequent. Only 21% of patients remained free of warts 2 weeks after completing treatment, and subsequent recurrences were noted in all patients available for long-term follow-up, which is a common limitation of ablative therapy for genital warts. CONCLUSION: Podofilox 0.5% solution is effective in treating penile warts and is well tolerated in a self-administered regimen. Podofilox 0.5% offers potential advantages in safety and cost over podophyllin resin therapy of genital warts. PMID- 2186624 TI - Anticarbohydrate autoantibodies to sialidase-treated erythrocytes and thymocytes in serum from patients with pulmonary sarcoidosis. AB - PURPOSE: The presence of immunoglobulins and complement in sarcoid granulomata and bronchoalveolar lavage from patients with sarcoidosis suggests that humoral mechanisms may be of importance in granuloma formation. To test this hypothesis, we examined the possibility that antibodies to specific tissue carbohydrates causing alterations and/or dysfunction of immunocompetent cells might be present during sarcoidosis. Because we had previously shown the presence of sialidase activity in bronchoalveolar lavage from these patients, we have looked for the presence of antibodies that recognize sialidase-treated erythrocytes (mostly antigalactose) in the serum of patients with sarcoidosis. Since thymocytes are spontaneously recognized by peanut agglutinin, a lectin that binds galactose, the reactivity of serum from sarcoidosis patients with normal or neuraminidase treated thymocytes has also been studied. PATIENTS AND METHODS: Serum samples were obtained from the venous blood of patients with biopsy-proven sarcoidosis, most of whom had no extrathoracic symptoms. The mean patient age was 31 years, with a range from 21 to 57 years. There were 12 women and 19 men, and 10% of the patients were smokers. Sarcoidosis was classified as recent if symptoms had been present for less than 1 year and chronic if symptoms had been present for longer than this. Control serum samples were obtained from patients with idiopathic pulmonary fibrosis (n = 9) and from healthy volunteers (n = 15). Furthermore, serum from patients who had previously had sarcoidosis but in whom cures had been achieved was also studied (n = 6). RESULTS: Sialidase-treated erythrocytes were lysed in autologous serum upon incubation at 37 degrees C providing that the serum came from a patient with active disease. Serum from either normal volunteers or patients with resolved sarcoidosis had no significant cytotoxic activity. Lysis proceeded through activation of the classical complement pathway following fixation of autoantibodies. These antibodies were predominantly of the IgM class. They were able to agglutinate neuraminidase-treated thymocytes, whereas untreated thymocytes did not fix the antibodies. Carbohydrate inhibition experiments demonstrated that these antibodies are mostly galactose specific. As this sugar is located immediately below the sialic acid residues in the carbohydrate moiety of membrane glycoconjugates, it is unmasked following sialidase treatment. CONCLUSION: Since galactose has been shown to be present on the membrane of certain subsets of immunocompetent cells (e.g., lymphocytes and macrophages either spontaneously or after stimulation), it is possible that antigalactose antibodies may affect the metabolism of these cells, leading to some of the immune dysfunctions that are observed during sarcoidosis. PMID- 2186625 TI - Pyarthrosis in patients with rheumatoid arthritis: a report of 13 cases and a review of the literature from the past 40 years. AB - PURPOSE: The purpose of this study is to report 13 cases and review the literature for pyarthrosis occurring in the setting of rheumatoid arthritis (RA). Special emphasis is placed on evaluating both the changing, as well as the constant, features of this complication and on assessing diagnostic and therapeutic aspects that have a bearing upon outcome. PATIENTS AND METHODS: A retrospective review of records from our institution revealed 13 cases of pyarthrosis in patients with RA over the past 14 years. Information obtained included patient demographics, RA history, concomitant illnesses and medications, length of symptoms prior to the diagnosis of pyarthrosis, peri-articular manifestations, probable source of infection, joint(s) involved, relevant laboratory data, and information on treatment and outcome based on initial surgical therapy versus closed needle drainage. In addition, 213 cases from 45 citations were reviewed for similar information. RESULTS: Our series was notable for a high percentage of associated serious medical illnesses and peri-articular manifestations of the pyarthrosis (i.e., sinus tract formation, concomitant septic bursitis, or infected synovial cyst). The erythrocyte sedimentation rate was a useful monitor of adequate therapy and was often a signal of recurrent infection. In all patients, the skin was the major source of infection. The mortality from pyarthrosis has declined over the past 40 years but is still unacceptably high, especially in patients with polyarticular involvement. Preliminary observations suggest that an initial surgical approach to joint drainage may be preferable to closed needle drainage in order to improve joint outcome in patients with RA and pyarthrosis. CONCLUSION: Pyarthrosis occurring in patients with RA continues to produce unacceptable morbidity and mortality despite 40 years' experience. Earlier recognition (which may include peri articular features) and perhaps an aggressive surgical approach to drainage may improve the prognosis. PMID- 2186626 TI - Pill-induced esophageal strictures: clinical features and risk factors for development. AB - Clinical data from five subjects with pill-induced esophageal strictures and from the English-language literature on pill-induced esophageal damage were reviewed to determine risk factors for stricture development and to characterize this complication. Including our five cases, 195 patients with pill-induced damage and 39 patients with pill-induced strictures have been reported to date. Seventy eight percent of the strictures were located in the proximal or mid-esophagus. Potassium chloride or quinidine preparations were incriminated in 60% of cases and were more likely to produce stricture than other medications commonly associated with esophageal damage (e.g., tetracycline). Older age, male gender, left atrial enlargement, ingestion of sustained-release formulations, and prior esophageal structural abnormality were all more commonly present in the subset with strictures (p less than 0.05 for each), even after appropriately controlling for medication. A logistic regression analysis revealed that older age and ingestion of sustained-release formulations were the most significant independent factors associated with stricture development (p less than 0.0001 for each). These findings indicate that stricture formation from pill-induced esophageal damage is dependent upon host-related factors as well as the caustic nature of the pill. PMID- 2186627 TI - Hypokalemia in the "beautiful people". PMID- 2186629 TI - Susceptibility to nucleoside analogues of zidovudine-resistant isolates of human immunodeficiency virus. AB - The emergence of human immunodeficiency virus resistant to 3'-azido-3' deoxythymidine (zidovudine, AZT) in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex has been documented. Isolates from non AZT-treated persons or those who had received AZT for less than six months showed a narrow range of susceptibility to the drug; on the other hand, isolates from those who had received AZT for six months or more consistently showed reduced susceptibility. Five highly AZT-resistant isolates were also insensitive to other compounds containing a 3'-azido group. No cross-resistance was found to other nucleoside analogues, including 2',3'-dideoxycytidine and 2',3'-dideoxyinosine. That cross-resistance occurred only in compounds containing a 3'-azido group suggests that mutations in the reverse transcriptase gene prohibit the enzyme from using nucleoside triphosphate containing a 3'-azido group. Progressive, stepwise increases in resistance have been associated with the sequential accumulation of specific amino acid changes in the reverse transcriptase gene. It is not yet known whether the resistant phenotype as determined in vitro results in clinical resistance to AZT. The gradual appearance of resistant isolates, the variable course of human immunodeficiency virus infections, and the absence of a consistent pattern of resurgent p24 antigen will make the emergence of AZT resistance difficult to correlate with clinical status or other markers. The combination of AZT with other drugs that do not share cross-resistance is a promising area for investigation to identify regimens that are more active and less likely to induce resistance. PMID- 2186628 TI - Recurrent nocturnal hypoglycemia in an insulin-dependent diabetic patient receiving a small daily dose of insulin. PMID- 2186631 TI - Hypothyroidism in the elderly. AB - This review describes the changes in thyroid physiology with aging and notes that normal thyroid status is maintained with advanced age. The increased frequency of hypothyroidism in the elderly is stressed with consideration given to the multiple possible etiologies. The natural history of hypothyroidism is considered as evidenced by the various hormonal abnormalities in subjects with autoimmune thyroiditis and patients previously treated with radioiodine. The potential significance of subclinical hypothyroidism is discussed in regard to nonspecific symptoms and subtle cardiovascular manifestations. The problems in the clinical and laboratory diagnosis of hypothyroidism are reviewed with emphasis on the high index of suspicion and cautious interpretation of plasma thyroxine and thyroid stimulating hormone (TSH) levels required. Finally the potential problems in treating hypothyroidism in the elderly are discussed in regard to dosage requirements and the need to avoid subclinical hypothyroidism by using the ultrasensitive TSH assay. PMID- 2186630 TI - Ancrod causes rapid thrombolysis in patients with acute stroke. AB - Clot lysis is desirable in patients with thrombi in arteries and arterioles by a safe rapidly-acting thrombolytic agent. Ancrod cleaves fibrinogen; the resulting circulating ancrod-fibrin stimulates fibrinolysis. Ancrod action and effect were studied in 20 patients with acute developing stroke in a double-blind, placebo controlled study. Patients were randomly assigned to one of two treatment groups, and received either normal saline or ancrod 0.5 mu/kg in normal saline administered as a constant-rate intravenous infusion over 6 hours. Subsequent doses of ancrod (or saline placebo) were determined daily thereafter for a total treatment period of 7 days. Neither bleeding nor re-thrombosis occurred within the 90 day follow-up period. That ancrod acted rapidly was shown by a significant decrease in functional plasminogen activator inhibitor (PA-I) within 60 minutes, and by significant elevations of fibrin(ogen) degradation products (FDP) and D dimer within 3 and 4 hours. The biological effect of fibrinolysis in ancrod infused patients was demonstrated by a greater improvement in stroke score when compared to those infused with saline. PMID- 2186632 TI - Control of renal function during intrarenal infusion of endothelin. AB - It has been demonstrated that bolus injections of a vasoconstrictor derived from endothelial cells, endothelin 1 (ET-1), constricts isolated arteries and increases blood pressure in animals when infused intravenously. The purpose of this study was to examine the direct effects of intrarenal infusions of ET-1 on renal function at doses that do not alter systemic arterial pressure. The effects of ET-1 on renal hemodynamics and electrolyte excretion were examined during 40 min of intrarenal infusions of ET-1 at rates of 1.15 and 5 ng.kg-1.min-1. Infusion of ET-1 (1.15 ng.kg-1.min-1) resulted in a transient increase in renal blood flow (RBF) followed by a progressive vasoconstriction, which reduced RBF by 23%. ET-1 decreased glomerular filtration rate (GFR) and had no significant effect on filtration fraction. Intrarenal infusion of ET-1 (1.15 ng.kg-1.min-1) had no effect on fractional excretion of sodium (FENa) or potassium. Infusion of ET-1 at a higher dose (5 ng.kg-1.min-1) produced further reductions in RBF, GFR, and FENa. These data indicate that ET-1 is a potent renal vasoconstrictor that could play a role in controlling renal hemodynamics. PMID- 2186633 TI - Kinetics and Na independence of amino acid uptake by blood side of perfused sheep choroid plexus. AB - The kinetic constants and sodium independence of amino acid uptake by the basolateral face (blood side) of the isolated perfused choroid plexus of the sheep were investigated. Uptake of 3H-labeled L-alanine, glycine, L-glutamine, L leucine, L-glutamate, and L-lysine was not significantly inhibited when the sodium level of the perfusate was lowered to less than 6 mM. The cerebrospinal fluid (CSF) secretion rate was, however, reduced by 65.6%. The Michaelis constants for L-serine, glycine, L-phenylalanine, L-glutamate, and L-arginine were measured and varied between 25.4 microM for L-arginine and 2.6 microM for L glutamate. The Vmax for the amino acids varied by about the same range as Km, with L-serine having the highest Vmax of 28.8 nmol.min-1.g-1, and L-phenylalanine having the lowest at 4.6 nmol.min-1.g-1. At normal plasma concentrations of 30 155 microM for individual amino acids, the carriers for glycine, L-phenylalanine, and L-glutamate would be almost fully saturated (greater than 90%), while those for L-serine and L-arginine would be greater than 60% saturated. This restricted uptake of amino acids by the basolateral face of the choroid plexus, coupled to clearance of these substances out of the CSF (5), could account for the low levels in the CSF compared with that in the plasma. PMID- 2186634 TI - Kinetics of system A amino acid uptake by muscle: effects of insulin and acute uremia. AB - We found that acute renal failure (ARF) depresses maximal responsiveness to insulin of system A amino acid transport in muscle [Maroni, Karapanos, and Mitch. Am. J. Physiol. 251 (Renal Fluid Electrolyte Physiol. 20): F74-F80, 1986]. To examine mechanisms for this change, we measured the kinetics of system A in response to insulin and ARF in epitrochlearis muscle. Insulin stimulation increased the diffusion constant (KD) approximately twofold in muscles from both ARF and control rats, suggesting that insulin can modulate nonsaturable alpha (methylamino)isobutyrate uptake. Compared with basal values, insulin did not significantly change maximal transport velocity (Vmax) in ARF or control rats; however, insulin decreased Michaelis constant (Km) by 79 and 63%, respectively. Inhibition of protein synthesis with cycloheximide did not prevent stimulation of system A by insulin. Acute uremia had no effect on nonsaturable uptake or basal system A kinetics. However, ARF produced opposing effects on insulin-stimulated system A kinetics. There was a approximately 47% decrease in Vmax, which was partially offset by a 66% reduction in Km. In summary, both insulin and ARF modulate system A kinetics by mechanisms that are independent of protein synthesis. PMID- 2186635 TI - Effect of Na and Cl infusion on loop function and plasma renin activity in rats. AB - Inhibition of plasma renin activity (PRA) by saline has been shown to be related to a specific effect of chloride. The purpose of this study was to test the hypothesis that inhibition of renin release by selective chloride infusion in the rat is related to increased chloride transport in the thick ascending limb of the loop of Henle (TALH). Measurements of loop of Henle function were obtained by micropuncture before and after a 5% body wt infusion of solutions containing either 0.15 mol/l NaCl, 0.15 mol/l lysine monohydrochloride (LysCl), or 0.15 mol/l Na-assorted anions (NaAA). Both NaCl and LysCl infusion lowered PRA (60.8 +/- 11.9 to 22.6 +/- 3.7 ng angiotensin I (ANG I).ml-1.h-1 and 53.3 +/- 6.8 to 34.5 +/- 4.6 ng ANG I.ml-1.h-1; P less than 0.05), whereas NaAA infusion had no effect on PRA (66.7 +/- 15.1 to 59.1 +/- 12.4 ng ANG I.ml-1.h-1). Analysis of late proximal and early distal fluid showed that chloride transport in the TALH was significantly elevated by infusion in all three groups, and there were no differences among the groups after infusion. Distal chloride concentration increased in the NaCl and LysCl groups (26 +/- 2 to 37 +/- 1 meq/l and 26 +/- 2 to 36 +/- 2 meq/l; P less than 0.05), but distal chloride concentration decreased in the NaAA group (28 +/- 2 to 22 +/- 1 meq/l; P less than 0.05). There was no correlation between PRA and fluid flow rate or chloride delivery to the distal tubule.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186636 TI - Possible endothelial modulation of prostaglandin-stimulated renin release. AB - Studies were run to determine whether the renal microvascular endothelium influences renin release. Blood-free rat renal cortical slices were incubated in a bicarbonate buffer for 60 min and sampled at 30 and 60 min to determine renin concentration and at 60 min for prostaglandin (PG) E2 and I2 (6-keto-PGF1 alpha) synthesis. Stimulation by 10(-6) M melittin of endogenous PGs simultaneously increased renin release, PGE2, and PGI2 synthesis, and all were inhibited by 1.6 x 10(-6) M meclofenamate. Renin release was stimulated with isoproterenol [26.2 +/- 2.4 ng angiotensin I (ANG I) .h-1.mg-1.30 min-1; P less than 0.001], PGI2 (32.3 +/- 7.4 ng ANG I.h-1.mg-1.mg-1.30 min-1; P less than 0.005), and PGE2 (25.7 +/- 2.8 ng ANG I.h-1.mg-1.30 min-1, P less than 0.001). Acetylcholine did not affect basal renin but potentiated the response to PGE2 by 80% (46.0 +/- 5.8 ng ANG I.h-1.mg-1.30 min-1; P less than 0.001). Atropine (10(-7) M) reversed this potentiation. Deendothelialization of renal microvessels with H2O2 eliminated PGI2, but neither PGE2 nor renin release, and reversed acetylcholine-potentiation of PGE2-stimulated renin release as did meclofenamate. Hemoglobin increased PGE2 stimulated renin similarly to acetylcholine. These studies suggest that stimulating the endothelium with acetylcholine results in selective potentiation of PGE2-stimulated renin release, which may be mediated through some cyclooxygenase product and is independent of endothelium-derived relaxing factor. Thus the renal endothelium may influence or modulate renin release. PMID- 2186637 TI - Measurement of renin secretion in single perfused rabbit glomeruli. AB - A new technique is presented that allows the measurement of the renin secretion rate of single rabbit glomeruli during in vitro perfusion at controlled afferent arteriolar perfusion pressure. Rabbit glomeruli with intact afferent arteriole and Bowman's capsule are obtained by microdissection and cannulated with a pipette system that allows continuous afferent arteriolar pressure measurement. The renin secretion rate of 10 glomeruli, perfused at 40 mmHg, was measured in 15 min intervals with an antibody-trapping microassay. Renin secretion rate was low relative to total renin content (1.2-2.0% of content/perfusion h) and increased three- to fivefold in response to isoproterenol (10(-5) M). The afferent arteriole contracted to norepinephrine (10(-5) M) in each instance. This novel, although difficult, technique allows the study of renin release in vitro at controlled perfusion pressure, without the interfering effects of the macula densa, arterial angiotensin II, and the adrenergic nervous system. It should allow a new perspective on issues such as the pressure-flow dependence of renin release and the interaction of the afferent arteriolar endothelium with the renin secreting juxtaglomerular cells. PMID- 2186638 TI - Systemic and local effects of endotoxin on canine gracilis muscle vascular conductance. AB - To define the site and mechanism of action that endotoxin has on the peripheral vasculature, an in situ constant-flow double-canine gracilis muscle (GM) preparation was utilized. During systemic endotoxemia, one GM was innervated and the other was denervated during a 30-min intravenous infusion of 2 mg/kg endotoxin. Significantly increased vascular conductance (URP) in the denervated GM (106 +/- 26%) occurred compared with the innervated GM (50 +/- 7%), which suggests that decompensation is not totally dependent on neural depression. During local endotoxemia, with both GMs either intact or denervated, one GM was infused intra-arterially for 30 min with a dose of endotoxin calculated to provide a blood concentration similar to that achieved during systemic endotoxemia, whereas the other GM was infused with the vehicle. The URPs did not change significantly in either the saline or endotoxin GMs. Therefore, endotoxin does not act directly on peripheral vasculature or totally through depression of the autonomic nervous system. It apparently interacts with a systemically dependent mechanism to release a vasodepressor substance that is transported to the peripheral vasculature causing relaxation of vascular tone. PMID- 2186639 TI - Comparative responses to endothelin 2 and sarafotoxin 6b in systemic vascular bed of cats. AB - Cardiovascular responses to endothelin 2 (ET-2) and sarafotoxin 6b (S6b) were investigated in the cat. ET-2 (0.1-1 nmol/kg iv) decreased or elicited biphasic changes in arterial pressure (AP), whereas S6b (0.1-1 nmol/kg iv) only decreased AP. Central venous pressure (CVP), cardiac output (CO), and pulmonary arterial pressure (PAP) were increased. ET-2 produced biphasic changes in systemic vascular resistance (SVR), whereas S6b decreased SVR at the two lower doses and caused a biphasic change at the 1 nmol/kg dose. The effects of ET-1 and ET-2 were similar, whereas the effects of S6b were similar to ET-3. ET-2 and S6b had small effects on right ventricular contractile force and caused transient increases in heart rate. Distal aortic blood flow was increased in response to all doses of both peptides, whereas increases in carotid blood flow were observed only in response to the higher doses of ET-2 and S6b. ET-2 produced dose-dependent decreases in superior mesenteric artery (SMA) blood flow, whereas decreases in SMA flow in response to S6b were observed only at the 1 nmol/kg dose. Renal blood flow was decreased significantly only at the higher doses of ET-2 and S6b. The present data show that ET-2 and S6b can produce both vasodilation and vasoconstriction in the systemic and regional vascular beds of the cat and demonstrate previously unrecognized vasodilator activity in response to S6b. It is concluded that ET-2 and S6b produce complex cardiovascular responses in the anesthetized cat. PMID- 2186640 TI - Cerebrovascular transport of [125I]quinuclidinyl benzilate, [3H]cyclofoxy, and [14C]iodoantipyrine. AB - The transport rate constants across rat brain capillaries of a muscarinic acetylcholine receptor antagonist, [125I]quinuclidinyl benzilate (IQNB), an opiate receptor antagonist, [3H]cyclofoxy (CF), and a highly diffusible blood flow indicator, [14C]iodoantipyrine (IAP), were determined by the indicator diffusion technique and a model that includes a distribution of capillary transit times and a homogeneous distribution of the test compound in the tissue parenchyma. The mean influx extraction ratio (E1) of IAP was greater than 0.91, and E1 for CF and IQNB was 0.56-0.79 and 0.34-0.46, respectively. The order of lipid solubility was IQNB greater than IAP greater than CF; the apparent discrepancy (high lipid solubility and low permeability) of IQNB was partly due to intravascular binding to plasma protein and red blood cells. The observed initial tissue distribution volumes (lambda 1, ml/g brain) for IQNB (0.09-0.17), CF (0.51), and IAP (0.71) were compared with those estimated for the unbound free ligand in blood (lambda a, ml/g brain; IQNB = 1.3-2.3, CF = 0.88, and IAP = 1.4). These findings suggest that the binding of lipid-soluble radioligands and drugs to plasma proteins and red blood cells can be a major determinant of transport across the blood-brain barrier and the apparent distribution volume of the ligand in brain tissue. PMID- 2186641 TI - Effects of dietary protein intake on vasoactive hormones. AB - Vasoactive hormonal response to two levels of dietary protein intake was studied in seven healthy adult volunteers. The subjects were randomly placed on a 2-g.kg 1.day-1 (high) or 0.55-g.kg-1.day-1 (low) diet using a crossover design and were studied on the morning of the 5th day and again after 24 h of indomethacin treatment. Plasma renin activity (PRA), aldosterone, vasopressin, and urinary excretion of 6-ketoprostaglandin F1 alpha (PGF1 alpha) were significantly higher on the high-protein diet despite constancy of body weight, blood pressure, pulse, urinary sodium and potassium excretion, and plasma amino acid levels. After treatment with cyclooxygenase inhibitor indomethacin, 6-keto-PGF1 alpha excretion was equalized, but the elevated PRA and aldosterone levels persisted on the high protein diet, suggesting that PRA and aldosterone elevations do not depend entirely on prostanoid release. We conclude that chronic augmentation of dietary protein intake is accompanied by alterations of vasoactive hormones, which persist for up to 10 h postprandially and are independent of elevated plasma amino acid levels. Such hormonal alterations may mediate some of the dietary protein-mediated changes in renal hemodynamics. PMID- 2186642 TI - Model study of placental water transfer and causes of fetal water disease in sheep. AB - The purpose of the computer simulation was to use experimentally measured parameters of placental water transfer to compute conceptual water acquisition during the last third of ovine pregnancy and to evaluate the possible role of each of these parameters in the pathophysiology of polyhydramnios. Total conceptual water at birth was almost insensitive to the value of the placental filtration coefficient. It was more sensitive to fetal and maternal placental blood flows, the concentrations of actively transported or metabolically produced solutes in fetal plasma (bicarbonate, fructose, alpha-amino acids, urea, lactate), and the hydrostatic pressure difference across the placental barrier. It was quite sensitive to the NaCl reflection coefficient and permeability. We conclude that the actively transported or produced solutes in fetal plasma constitute a primary driving force. The opposing diffusion gradient of NaCl, and to a much lesser extent that of glucose, are essential to restrain the process. The causes of polyhydramnios in this species are, in order of probability, an increase in the placental diffusion permeability of NaCl, a decrease in the placental reflection coefficient for NaCl, or an increase in the concentration of an osmotically effective solute in fetal plasma, by active transport or metabolic production. PMID- 2186643 TI - Kikuchi-Fujimoto disease mimicking malignant lymphoma. AB - Histiocytic necrotizing lymphadenitis is a rare, benign entity described independently both by Kikuchi and Fujimoto et al. This disease, which has a broad morphologic spectrum, can readily be mistaken for malignant lymphoma. Our report on the morphologic features in 10 selected cases of this disease highlights those features that mimicked lymphoma and those that helped us to make an accurate diagnosis. The distinctive features were (a) pathologic areas, which are pale and do not occupy the entire lymph node; (b) preserved sinuses in the uninvolved areas; (c) prominent mottling by histiocytes or transformed lymphoid cells in the nonpathologic areas; (d) frequent absence of overt necrosis; (e) presence of benign histiocytes with moderate to marked nuclear irregularities and scanty to moderate cytoplasm that resembled cleaved cells; (f) variable amounts of nuclear debris, usually extracellular; (g) presence of so-called plasmacytoid T cells at the periphery of or immediately outside the pathologic areas; (h) moderate numbers of mitotic figures and transformed lymphoid cells of medium and large size (immunoblasts); and (i) absence of inflammatory and granulomatous reaction. Because overt necrosis is often absent and histiocytes resemble cleaved cells, we support the suggestion that this entity should be called "Kikuchi-Fujimoto disease" rather than "histiocytic necrotizing lymphadenitis." PMID- 2186644 TI - Mixed hyperplastic adenomatous polyps/serrated adenomas. A distinct form of colorectal neoplasia. AB - We present the clinicopathologic characteristics of 110 colorectal mixed hyperplastic adenomatous polyps (MHAP) that exhibited the architectural but not the cytologic features of a hyperplastic polyp. They are compared with 60 traditional adenomas, 40 hyperplastic polyps, and five colonic polyps that contained admixed but well-defined hyperplastic and adenomatous glands (HP/AD). The patients with MHAP ranged in age from 15 to 88 years (mean, 63 years). Five patients had two or more (up to seven) lesions. MHAP measured 0.2-7.5 cm in diameter. They were distributed throughout the colorectum, but a slight preponderance of large lesions (more than 1.0 cm) occurred in the cecum and appendix. All MHAP were characterized by a serrated glandular pattern simulating that seen in hyperplasia (27% of MHAP were initially diagnosed as hyperplastic polyps). However, MHAP were distinguished by the presence of goblet cell immaturity, upper zone mitoses, prominence of nucleoli, and the absence of a thickened collagen table. Although surface mitotic activity, nuclear pseudostratification, and nuclear cytoplasmic ratio were greater in MHAP than in hyperplastic polyps, they were slightly less than in traditional adenomas. Thirty seven percent of MHAP contained foci of significant dysplasia; 11% contained areas of intramucosal carcinoma. We conclude that these lesions reflect a morphologically unique variant of adenoma and suggest that they be termed "serrated adenoma" in order to emphasize their neoplastic nature. We further offer the hypothesis that MHAP may arise from the neoplastic transformation of a more differentiated cell in the crypt than the traditional adenoma. PMID- 2186645 TI - Histiocytoid (epithelioid) hemangioma of the testis. The so-called vascular variant of "adenomatoid tumor". AB - Adenomatoid tumors are well-recognized neoplasms generally considered to be of mesothelial derivation. We describe an unusual vascular neoplasm that arose in the testis of a 29-year-old and resembled an adenomatoid tumor by light microscopy. An orchiectomy was performed, and the patient is alive and disease free 3 years later. The 2-cm tumor was composed of small tubules lined by mesothelial-like cells with uniform, vesicular nuclei. However, some lumina contained erythrocytes, and immunohistochemically, the luminal cells reacted with antibodies to vimentin, Factor VIII-related antigen, and Ulex europaeus I lectin but not cytokeratin or epithelial membrane antigen. A cuff of muscle-specific actin-positive cells surrounded the luminal cell layer. This adenomatoid-like vascular neoplasm is more properly interpreted as a histiocytoid (epithelioid) hemangioma. Although some authors have considered microscopically similar lesions to represent a vascular variant of adenomatoid tumor, we prefer to reserve the term "adenomatoid tumor" for microscopically appropriate proliferations that have mesothelial features. PMID- 2186646 TI - Exocrine pancreatic tissue in human liver: a metaplastic process? AB - Numerous microscopic foci of exocrine pancreatic tissue consisting of acini and small ductules were distributed throughout the liver of a 41-year-old patient with severe posthepatitic cirrhosis. The acinar cells were characterized by abundant zymogen granules on electron microscopic examination and a strong reaction with antibodies to alpha-amylase on immunoperoxidase staining. The pancreatic tissue was associated with proliferations of bile ductules within areas of fibrosis. No relationship with hepatocytes was observed. A metaplastic origin of the pancreatic tissue from the intrahepatic biliary epithelium is suggested. PMID- 2186647 TI - Postoperative sore throat. A comparison after premedication with papaveretum/hyoscine or temazepam. AB - A randomised double-blind trial was conducted to study the use of two commonly used premedication regimens and the subsequent incidence of sore throat. Fifty adult patients who underwent routine surgery were anaesthetised in a standard fashion after premedication with papaveretum and scopolamine or temazepam, and interviewed after operation to assess the presence of sore throat. A significantly higher incidence of sore throat was associated with the use of papaveretum and scopolamine. PMID- 2186648 TI - Neuroleptic malignant syndrome in the intensive therapy unit. AB - A case of the neuroleptic malignant syndrome occurred in a 40-year-old male after administration of chlorpromazine while on an Intensive Therapy Unit. Treatment with dantrolene sodium was successful, and a muscle biopsy was examined in the recovery phase of the illness. The importance of this condition and the difficulties in establishing a diagnosis at an early stage in patients on an Intensive Therapy Unit are discussed, along with implications for treatment. PMID- 2186649 TI - A low flow open circle system for anaesthesia. Part 2: Clinical evaluation. AB - A prototype valveless ventilator was attached by open deadspace tubing to a circle system and used to ventilate the lungs of 12 patients with low flows of anaesthetic gases for periods between 60 and 120 minutes during intra-abdominal surgery. Anaesthesia was induced with thiopentone and maintained with nitrous oxide 50% in oxygen and enflurane. This was reduced to 2 litres/minute after a 10 minute period of nitrogen wash out and stabilisation of anaesthetic gas concentration, with an initial anaesthetic gas flow of 6 litres/minute. The concentration of oxygen, carbon dioxide, nitrous oxide and enflurane were measured in the outflow from both the anaesthetic machine and the inspiratory limb of the circle system. The measured mean inspired oxygen and nitrous oxide concentrations showed no significant variation throughout the low flow period of the study. This new low flow open circle ventilation system appears to offer some advantages in terms of safety and versatility over other systems which are discussed. PMID- 2186650 TI - Propofol sedation after open heart surgery. A clinical and pharmacokinetic study. AB - One hundred adult patients who required mechanical ventilation after open heart surgery for coronary revascularisation were studied. All received a standard premedication and a high dose opioid anaesthetic. On arrival in the intensive care unit they were allocated randomly to receive either propofol or midazolam to maintain sedation within a predetermined range. Patients who received propofol underwent extubation of the trachea, using standard criteria, after a mean time (log-transformed) of 7.6 minutes after sedation for approximately 17 hours. The corresponding time was 125 minutes in those given midazolam. There were significantly higher morphine requirements during sedation, and higher arterial carbon dioxide tensions 30 minutes after extubation of the trachea, in patients who received midazolam. Pharmacokinetic analysis in 20 patients showed that the elimination half-life of propofol was prolonged (470 minutes) and clearance was reduced (1.14 litres/minute) compared with subjects who had not undergone cardiopulmonary bypass. The rapid clinical recovery was reflected in a rapid redistribution half-life (13.4 minutes), but this was also longer than the redistribution time of 2-4 minutes in other patients. PMID- 2186652 TI - A Patent application. PMID- 2186651 TI - The effect of diclofenac and nefopam on postoperative dental pain. AB - Eighty-two outpatients who received general anaesthesia for surgical removal of maxillary or mandibular third molars were given either diclofenac 75 mg or nefopam 20 mg intramuscularly for postoperative pain control. They and the control group were also allowed oral paracetamol as required. The results showed that there was no significant pain relief from these single intramuscular injections. PMID- 2186653 TI - Anaesthetic agents and the ozone layer. AB - There is an important relationship between the stratospheric ozone layer and the absorption of potentially harmful ultraviolet-B radiation from the sun. Chlorofluorocarbons and halogenated hydrocarbons are commonly used chemicals which are implicated in the depletion of the ozone layer. Of the anaesthetic agents, halothane has the greatest potential for depleting ozone although, when compared with the global use of other chlorofluorocarbons and halogenated hydrocarbons, its current contribution to the problem is relatively small. PMID- 2186654 TI - The effect, on injection pain, of adding lignocaine to propofol. PMID- 2186655 TI - Oral ketamine premedication for paediatric cardiac surgery--a comparison with intramuscular morphine (both after oral trimeprazine). AB - In a single-blind controlled study, forty children with congenital heart disease were premedicated with oral trimeprazine 3 mg/kg and either intramuscular morphine 0.1 mg/kg or oral ketamine 10 mg/kg. Cardiovascular and respiratory effects of premedication and degree of sedation induced were similar in the two groups of patients. Oral ketamine is a safe and effective premedicant in this group of patients. PMID- 2186656 TI - The Mayfair Gas Company. PMID- 2186657 TI - An Australian's reflections on Macintosh and Oxford. PMID- 2186658 TI - A double-blind comparison of epidural bupivacaine and bupivacaine-fentanyl for caesarean section. AB - The effect of adding fentanyl 100 mcg to bupivacaine 0.5% plain to establish epidural anaesthesia for elective caesarean section was investigated in a randomised, double-blind study of sixty healthy women. The quality of intraoperative analgesia as assessed by both patients and anaesthetists was significantly improved with fentanyl. The onset and duration of sensory anaesthesia, degree and duration of motor block, and other characteristics of epidural anaesthesia were unaltered. No adverse maternal side-effects (except mild pruritus) were noted and neonatal outcome was unaffected. The pharmacokinetics of epidural fentanyl administration were investigated by plasma fentanyl assays from maternal and cord blood taken at delivery. Epidural bupivacaine-fentanyl combination is a valuable therapeutic approach to the conduct of epidural anaesthesia for caesarean section in healthy women and foetuses. Further neonatal evaluation of the premature or compromised foetus is suggested before the universal application of this technique. PMID- 2186659 TI - The Lidwill machine. PMID- 2186660 TI - The perioperative effects of oral premedication in children. AB - The pre- and postoperative effects of oral diazepam (0.5 mg/kg), trimeprazine (4 mg/kg), pentobarbitone (3 mg/kg) and a placebo were compared in a randomized double-blind clinical trial in 149 children, aged one to ten years, undergoing adenotonsillectomy. The anaesthetic was standardised and each patient received intraoperative intramuscular papaveretum (0.3 mg/kg). Preoperative sedation was assessed in the ward before transfer onto the theatre trolley, on leaving the ward, on arrival on the theatre floor, on arrival in the induction room and on induction of anaesthesia. There was no significant difference in sedation between the four drug groups except for the placebo group which had a significantly greater unsatisfactory rating at the stage of induction of anaesthesia (P = 0.001). There were no differences in waking times between the diazepam, pentobarbitone and placebo groups, but the trimeprazine group's waking times were significantly prolonged (P less than 0.001). However, the trimeprazine group exhibited significantly less distress in the recovery unit (P = 0.02) and had half the incidence of vomiting (P less than 0.001) than did the other premedication groups. PMID- 2186661 TI - Gastric aspiration at the end of anaesthesia does not decrease postoperative nausea and vomiting. AB - Two hundred and one women undergoing elective abdominal hysterectomy were anaesthetised with isoflurane in nitrous oxide and oxygen. At the end of anaesthesia the stomach was aspirated in half of the patients, selected in random order. In the other half no aspiration was performed. Incidence and severity of emesis (none, nausea, retching or vomiting) was assessed during the first 24 hours after operation. Emesis was similar after the operation regardless of aspiration of the stomach (overall emesis, 79% and 70% for those whose stomach had and had not been aspirated, respectively). The incidence at all times during the 24 hours was similar in both groups. The results suggest that gastric aspiration at the end of anaesthesia has no major effect on the incidence or severity of postoperative emesis in patients undergoing abdominal hysterectomy. PMID- 2186662 TI - Continuous renal replacement in the critically ill. PMID- 2186663 TI - Suxamethonium and hyperkalaemia. AB - Severe life-threatening hyperkalaemia may occur following administration of suxamethonium during certain periods after burns, neurological injuries, and in certain other conditions. Although this response is well-known, there is disagreement about when it may occur. This review describes the normal hyperkalaemic response to suxamethonium, the factors affecting it, the conditions in which it may be exaggerated, and the periods of high risk. PMID- 2186664 TI - Developmental cell death: morphological diversity and multiple mechanisms. AB - Physiological cell death is a widespread phenomenon in the development of both vertebrates and invertebrates. This review concentrates on an aspect of developmental cell death that has tended to be neglected, the manner in which the cells are dismantled. It is emphasized that the dying cells may adopt one of at least three different morphological types: "apoptotic", "autophagic", and "non lysosomal vesiculate". These probably reflect a corresponding multiplicity of intracellular events. In particular, the destruction of the cytoplasm in these three types appears to be achieved primarily by heterophagy, by autophagy and by non-lysosomal degradation, respectively. The various mechanisms underlying both nuclear and cytoplasmic destruction are reviewed in detail. The multiplicity of destructive mechanisms needs to be born in mind in studies of other aspects of cell death such as the signals which trigger it, since different signals probably trigger different types of cell death. PMID- 2186665 TI - Non-adaptive cellular immune responses as studied in euthymic and athymic nude rats. Spontaneous rejection of allogeneic lymphoid cell grafts by natural killer (NK) cells. AB - The athymic nude (rnu) rat lacks a functional thymus and normal alloreactive T cells. These animals, therefore, have been widely used as tools for studying thymus-independent immune responses. The absence of functional T cells would, to most investigators, indicate that these rats have a defective cellular immune defence. However, although rnu rats accept organ allografts infinitely, they are nevertheless capable of rejecting allografts consisting of lymphocytes or bone marrow cells with increased vigour, and this via antibody-independent mechanisms. These rejection phenomena have operationally been termed allogeneic lymphocyte cytotoxicity (ALC) and allogeneic bone marrow cell cytotoxicity (ABC). Unlike organ allograft immunity this kind of rejection requires no presensitization of the recipient and is surprisingly rapid: it commences within a few hours of i.v. injection of the allogeneic cells and is usually complete by 24 h. Moreover, products coded for by genes within, or closely linked to the major histocompatibility complex (MHC), are clearly involved in the interaction between effector and target cells, as grafted cells from MHC-congenic rat strains are vigorously rejected. In contrast to the defective T cell immune responses in athymic nude rats, the natural killer (NK) cell function is not impaired, and it has been suggested that the spontaneous rejection of MHC-incompatible lymphohematopoietic cells is in fact mediated by NK cells. If the MHC antigens themselves serve as targets in this kind of allorejection, this hypothesis is in apparent contrast with the prevailing view that recognition by NK cells is not guided by, or directed against, MHC-antigens on the target cell surface. Aging athymic nude mice and rats generate cells that rearrange and express T cell receptor (TCR) genes, and this has raised the possibility that T cells or T-like cells in athymic nude animals are responsible for ALC and ABC. This possibility urged the device of an in vitro test system for identification and further characterization of the effector cells in these rejection phenomena. Under appropriate conditions, cells from the rnu rat spleen or liver with natural killer function, i.e. the ability to lyse certain kinds of tumor cells in vitro, are also spontaneously cytotoxic for allogeneic small lymphocytes and bone marrow cells in vitro. Furthermore, these cells can be grown in vitro in the presence of interleukin 2 (IL-2) to generate populations of lymphokine-activated killer (LAK) cells, and these cells have the same spectrum of alloreactivity in ALC and ABC as the native NK cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186666 TI - The distribution of mesenchyme proteoglycan (PG-M) during wing bud outgrowth. AB - This study utilizes immunofluorescence to describe the distribution of several extracellular matrix molecules in the chick embryo during the process of limb outgrowth and the formation of precartilage condensations. A large chondroitin sulfate proteoglycan (PG-M) is detected at the wing level at Hamburger and Hamilton stage 14 in and under the dorsal ectoderm, and is associated with the basement membranes around the neural tube, notochord and pronephros, but not with other basement membranes. The galactose-specific lectin, peanut agglutinin (PNA), has a similar distribution except that it also binds to the dorsal side of the neural tube. PG-M is not detected in the limb mesenchyme until after stage 17, when it is present in the distal region, as is PNA-binding material. With further development of the wing bud, PG-M is present in the subectodermal mesenchyme, the mesenchyme at the distal tip and in the prechondrogenic core. After stage 22 PNA binding material becomes localized in the prechondrogenic core, the basement membranes under the apical ectodermal ridge, and the ventral sulcus. The distribution of these components (PG-M and PNA binding material) overlaps, but differs from that of type I collagen and fibronectin and basement membrane components, such as laminin, basement membrane heparan sulfate proteoglycan, and type IV collagen. Tenascin, on the other hand, is not detected in the limb bud until stage 25, after the appearance of cartilage matrix components such as type II collagen and cartilage proteoglycan (PG-H). These results are considered in relation to the formation of precartilage aggregates, and indicate that PNA binds to components in precartilage aggregates other than PG-M or tenascin. PMID- 2186667 TI - On the differentiation and origin of myoid cells in the avian thymus. AB - The avian thymus and its myoid cells were investigated paying special attention to the developmental and morphological differences between chick and quail. By means of light- and electron microscopy, and immunofluorescence technique using an anti-myosin antibody, the myoid cells were found to express characteristics corresponding to those of skeletal muscle cells. They change their appearance during embryonic development. In the chick the myoid cells become located singly and rounded, and their cross-striation disappears. In the quail they remain small, elongated, cross-striated, and become arranged in long cords. The origin of myoid cells was studied using the quail-chick marking technique: Cranial somites and the prechordal mesoderm were grafted from quail into chick embryos. After somite transplantation the host thymus does not contain graft-derived cells. The myoid cells are exclusively derived from the chick. After implantation of prechordal mesoderm, graft-derived quail cells are found in the central cores of all visceral arches and also within the early epithelial anlage of chimeric thymus. These findings indicate that the thymus myoid cells are derived from the axially located prechordal head mesoderm. PMID- 2186668 TI - Antigen-antibody complexes in experimental infection with Trichinella spiralis and their role in the development of kidney lesions. AB - The kidneys of rats, experimentally infected with Trichinella spiralis were studied by means of light and fluorescent microscopy. The results obtained suggest that this is a case of a proliferative intra- and extracapillary nephritis. Highest intensity of the pathological process was noted between the 30th and 50th day of the infection. The immunofluorescent reaction of kidney glomeruli demonstrated that the immune complexes were located predominantly in the basal membrane and the mesangium. The serological investigation showed that the maximum level of circulating immune complexes existed between 14th and 21st day after the infection. PMID- 2186670 TI - Childhood asthma: a rational approach to treatment. AB - Asthma is a common, but frequently underdiagnosed and undertreated, condition in childhood. In most children, the diagnosis of asthma can be made on the basis of history, physical examination, and simple investigations. Successful management of asthma is contingent upon both patient and parents having a clear understanding of the condition, the goals, and specific details of treatment. The majority of children with asthma can be managed by avoidance of provoking factors, and suppression of symptoms with drug therapy. Drug therapy should follow a logical scheme such that a child with mild, infrequent asthma attacks would receive intermittent bronchodilator therapy, whereas a child with severe chronic asthma would ultimately be treated with maintenance steroids. Response to therapy should be assessed by serial measurement of pulmonary function. Certain features peculiar to infantile asthma demand a modified approach to the management of asthma in this age group. PMID- 2186669 TI - High Staphylococcus aureus nasal carriage rate in patients with acquired immunodeficiency syndrome or AIDS-related complex. AB - Staphylococcus aureus has been reported to cause a high number of infections and septicemias, often related to intravenous catheters, in patients with acquired immunodeficiency syndrome (AIDS). Our objective was to assess the frequency of S. aureus nasal carriage among patients with AIDS or AIDS-related complex (ARC). The nasal carriage rate of S. aureus was determined within 24 hours of admission in 64 consecutively hospitalized patients with AIDS or ARC. Intravenous drug abusers were excluded. A control group of 64 patients with other diseases was also tested. Of 64 patients with AIDS or ARC, 35 (55%) were nasal carriers of S. aureus, compared with 18 (28%) of 64 control patients. Recent hospitalization did not influence carriage rate, nor did the recent use of antibiotics or zidovudine. The significant S. aureus carriage rate in patients with AIDS or ARC may contribute to the high incidence of intravenous catheter-related S. aureus infections in this population. PMID- 2186671 TI - Immunotoxicology: review of current status. AB - Our need to understand the potential adverse human health effects of environmental chemical exposure has coincided with an increased understanding of the immune system and an appreciation of its complex regulatory network. This has spawned a broad interest in the area of immunotoxicology within the scientific community as well as certain concerns in the public sector regarding chemical induced hypersensitivity and immunosuppression. The incidence of alleged human sensitization to chemicals has increased, in part, due to the fact that chemical companies are moving to larger and/or different markets. It has been estimated that 35 million Americans suffer from allergic disease of which 2% to 5% are from occupational exposure. Although there is not yet a clear understanding of dose response relationships or disease predisposition, there are many well-defined examples (isocyanates, anhydrides) of chemical sensitizers in humans and experimental animals. Evidence that chemicals suppress immune responses in humans is considerably less well established, although there is a public perception that chemicals generally cause immunosuppression. This perception has been fueled by highly publicized legal cases (ie, W.R. Grace and Agent Orange) and scientific controversies within the academic and industrial communities (Aldicarb). As a consequence of public pressure, the regulatory agencies are considering immunotoxicity testing guidelines. At the present, however, there are limitations on adequate human methodology and data that allow the extrapolation of animal data to assess accurately human risk.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186672 TI - Immunology of multiple sclerosis. PMID- 2186673 TI - Efficacy and safety of intranasal budesonide in the treatment of perennial rhinitis in adults and children. AB - The efficacy and safety of intranasal budesonide were evaluated in a placebo controlled double-blind study of 51 children (6 to 18 years) and 48 adults with perennial (allergic or nonallergic) rhinitis. The trial commenced with a 2-week baseline period without treatment for perennial rhinitis. This was followed by a treatment period of 4 weeks. Treatment was either intranasal budesonide 200 micrograms bid or matching placebo bid. Nasal symptoms were rated daily on a scale from 0 (absent) to 3 (severe). Safety was monitored by laboratory assessments (hematology, blood chemistry, urinalysis) as well as by rhinoscopy and recording of adverse events. Budesonide reduced the nasal symptoms as compared with baseline. The reduction was greater than in the placebo group and symptoms were improved significantly on budesonide treatment compared with placebo. Laboratory assessments demonstrated no differences between budesonide and placebo. Adverse responses to intranasal budesonide were few and minor, and compliance was high. Intranasal budesonide, 200 micrograms bid, thus appears to be efficacious, highly acceptable, and safe for the treatment of perennial rhinitis. PMID- 2186674 TI - Anaphylactoid reaction to ethanol. AB - We studied a 14-year-old boy who developed a pruritic rash and facial swelling after ingestion of beer or wine. A blinded challenge with purified ethanol was positive demonstrating ethanol itself to be the offending agent. An IgE-mediated reaction to ethanol or one of its metabolites as a hapten is possible, or the reaction may involve unusual metabolism of ethanol with accumulation of acetaldehyde and/or direct mast cell degranulation. PMID- 2186675 TI - Insulin allergy: re-evaluation after two decades. AB - We reevaluated IgE-mediated insulin allergy using sera obtained 16 to 21 years ago and, 1 and 5 years ago. All antibodies had specificity for human and bovine insulin. We reevaluated Prausnitz-Kustner reactivity after 15 years and the IgE antibody and cutaneous reactivity appeared unchanged. IgE-mediated insulin allergy appears to be declining. PMID- 2186676 TI - Isolation of Mycobacterium paratuberculosis from washed bovine ova after in vitro exposure. AB - To establish whether Mycobacterium paratuberculosis could be cultured from Dulbecco phosphate-buffered saline solution (DPBSS) and to test 3 sampling methods, DPBSS supplemented with 2% fetal bovine serum was inoculated with M paratuberculosis at concentrations of 10(4), 10(3), 10(2), 10(1), and 10(0) colony-forming units/ml. The inoculated media was sampled after mixing, after centrifugation, and after centrifugation and decontamination with 0.75% hexadecylpyridinium chloride. The samples were inoculated onto 3 slants of Herrolds egg yolk medium supplemented with sodium pyruvate and mycobactin J and 1 slant without mycobactin J. Mycobacterium paratuberculosis was isolated following all 3 sampling methods for all concentrations. Treatment with hexadecylpyridinium chloride decreased the number of colonies isolated. To test the efficacy of a 10 step wash procedure for removing M paratuberculosis from bovine ova, washed zona pellucida intact bovine ova were incubated in DPBSS supplemented with 2% fetal bovine serum containing concentrations of 10(4), 10(3), 10(2), 10(1), and 10(0) colony-forming units of M paratuberculosis/ml for 12 hours at 22 C. Ten zona pellucida intact ova were removed from each concentration and washed by passing through 10 changes of DPBSS supplemented with 15% fetal bovine serum. The media from each wash step was inoculated onto slants of Herrolds egg yolk medium. The ova were included with the tenth wash step. Mycobacterium paratuberculosis was isolated from 1 of 10 tenth-wash steps at the 10(4) concentration and 5 of 10 tenth-wash steps at 10(3). PMID- 2186677 TI - Cardiopulmonary effects of positive end-expiratory pressure in anesthetized, mechanically ventilated ponies. AB - To investigate the cardiopulmonary effects of positive end-expiratory pressure (PEEP), values of 10, 20, and 30 cm of H2O, were applied to anesthetized, dorsally recumbent, ventilated ponies. After IV induction of general anesthesia, PEEP was superimposed on controlled ventilation with 100% oxygen, and changes in gas exchange and cardiac function were measured. Increasing values of PEEP in these ponies caused a linear increase in the mean (+/- SEM) functional residual capacity, from a control value (zero end-expiratory pressure) of 1.7 +/- 0.24 L to 2.2 +/- 0.31, 2.9 +/- 0.32 and 3.4 +/- 0.3 L at PEEP of 10, 20, and 30 cm of H2O, respectively (P less than 0.05). Paralleling these changes, intrapulmonary shunt fraction decreased significantly (P less than 0.05) from a control value of 12.9 +/- 0.5%, to 7.5 +/- 1.1 and 2.1 +/- 0.6%, at PEEP of 20 and 30 cm of H2O, respectively. Cardiac output was decreased by increasing values of PEEP, from control value of 11.7 +/- 1.56 L/min to 9.9 +/- 1.51, 8.8 +/- 1.33 and 5.62 +/- 0.56 L/min at PEEP of 10, 20, and 30 cm of H2O, respectively. Related to decreasing cardiac output, tissue oxygen delivery also decreased as PEEP was increased, from control value of 2.0 +/- 0.09 L/min to 1.8 +/- 0.07, 1.6 +/- 0.06, and 1.03 +/- 0.04 L/min at PEEP of 10, 20, and 30 cm of H2O, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186678 TI - On the formation and regulation of anger and aggression. A cognitive neoassociationistic analysis. AB - Noting that a wide variety of unpleasant feelings, including sadness and depression, apparently can give rise to anger and aggression, I propose a cognitive-neoassociationistic model to account for the effects of negative affect on the development of angry feelings and the display of emotional aggression. Negative affect tends to activate ideas, memories, and expressive-motor reactions associated with anger and aggression as well as rudimentary angry feelings. Subsequent thought involving attributions, appraisals, and schematic conceptions can then intensify, suppress, enrich, or differentiate the initial reactions. Bodily reactions as well as emotion-relevant thoughts can activate the other components of the particular emotion network to which they are linked. Research findings consistent with the model are summarized. Experimental findings are also reported indicating that attention to one's negative feelings can lead to a regulation of the overt effects of the negative affect, I argue that the model can integrate the core aspect of the James-Lange theory with the newer cognitive theories of emotion. PMID- 2186679 TI - Gender and relationships. A developmental account. AB - This article argues that behavioral differentiation of the sexes is minimal when children are observed or tested individually. Sex differences emerge primarily in social situations, and their nature varies with the gender composition of dyads and groups. Children find same-sex play partners more compatible, and they segregate themselves into same-sex groups, in which distinctive interaction styles emerge. These styles are described. As children move into adolescence, the patterns they developed in their childhood same-sex groups are carried over into cross-sex encounters in which girls' styles put them at a disadvantage. Patterns of mutual influence can become more symmetrical in intimate male-female dyads, but the distinctive styles of the two sexes can still be seen in such dyads and are subsequently manifested in the roles and relationships of parenthood. The implications of these continuities are considered. PMID- 2186680 TI - Psychology and death. Meaningful rediscovery. AB - The place of death in psychology is reviewed historically. Leading causes for its being slighted as an area of investigation during psychology's early years are presented. Reasons for its rediscovery in the mid-1950s as a legitimate sector for scientific inquiry are then discussed, along with some vicissitudes encountered in carrying out research in the field. This is followed by a description of principal empirical findings, clinical perceptions, and perspectives emerging from work in the thanatological realm. The probability that such urgent social issues as abortion, acquired immunodeficiency syndrome (AIDS), and euthanasia, and such destructive behaviors as drug abuse, alcoholism, and certain acts of violence are associated with attitudes toward death offers a challenge to psychology to enhance the vitality of human response to maladaptive conduct and loss. Recognition of personal mortality is a major entryway to self knowledge. Although death is manifestly too complex to be the special sphere of any one discipline, psychology's position as an arena in which humanist and physicist-engineer cultures intersect provides us with a meaningful opportunity to advance our comprehension of how death can serve life. PMID- 2186681 TI - Bronchoalveolar lavage constituents in healthy individuals, idiopathic pulmonary fibrosis, and selected comparison groups. The BAL Cooperative Group Steering Committee. PMID- 2186682 TI - A decade of changing perceptions about neuropeptides. AB - The last decade has seen rapid growth in research with neuropeptides. During this time, we have been actively developing several concepts including the highly controversial one that peptides can cross the blood-brain barrier in intact form. One of the endogenous brain peptides used as a prototype for that concept, Tyr MIF-1, also was used for the concept of the existence of endogenous antiopiate neuropeptides. As has been true for most novel developments in science, these concepts, as well as some older ones, were met with a great deal of skepticism when first suggested. Eventually, however, amnesia concerning the difficulties initially encountered with the introduction of new concepts occurs, with their subsequent "rediscovery" made easier. PMID- 2186683 TI - Mechanism of autonomic dysreflexia. Contributions of catecholamine and peptide neurotransmitters. PMID- 2186684 TI - Bidirectional communication between the neuroendocrine and immune systems. Common hormones and hormone receptors. AB - The results reviewed here support a molecular basis for bidirectional communication between the immune and neuroendocrine systems. The main findings can be summarized as follows: First, cells of the immune system can synthesize biologically active neuroendocrine peptide hormones. Second immune cells also possess receptors for many of these peptides. Third, these same neuroendocrine hormones can influence immune function; and fourth, lymphokines can influence neuroendocrine tissues. The interesting conceptual advance is the idea that the immune system may serve as a sensory organ. Thus, the immune system may sense stimuli that are not recognized by the central or peripheral nervous system. These stimuli are termed noncognitive and include bacteria, viruses, tumors and antigens. The recognition of such stimuli is converted into information in the form of lymphokines, monokines, and hormones and a message received by neuroendocrine tissues. On the other hand, nervous system recognition of stimuli can also be converted into chemical signals that can be relayed to immune cells resulting in physiological changes. On this basis, we predict that the pathophysiology associated with infectious agents may be related to the types and amounts of hormones produced by the immune system. PMID- 2186685 TI - Is corticotropin-releasing factor a mediator of stress responses? PMID- 2186686 TI - Differential cloning approaches to the nervous system. PMID- 2186687 TI - The structure and macromolecular organization of type IX collagen in cartilage. PMID- 2186688 TI - Tissue-specific expression of type IX collagen. PMID- 2186689 TI - Type I and type III collagen interactions during fibrillogenesis. AB - There is some evidence that type I and type III collagens may be present in the same fibril. In order to demonstrate this, double labeling immunofluorescence microscopy and immunoelectron microscopy were performed with antibodies directed against the collagen molecule and the aminopropeptide domains of type I and type III procollagens using embryonic (postabortion) and adult human skin. Double indirect and protein A immunoelectron microscopy were carried out with 5- and 15 nm gold particles. Skin extracts were also studied by immunoblotting. Double immunofluorescence microscopy with antibodies against type I and type III collagen molecules revealed patterns of fluorescence that were identical in both fetal and adult skins. Immunofluorescence microscopy using an antibody directed against the aminopropeptide of type III procollagen labeled the entire dermis in both embryonic and adult skins. In contrast, although the aminopropeptide of type I procollagen was present throughout embryonic dermis, it was markedly reduced in adult dermis, except for the epidermo-dermal junction. Double immunoelectron microscopy of fetal skin revealed labeling of the aminopropeptide of type I and type III procollagens on the same thin (20-30 nm) fibrils. Large type I fibrils (90-100 nm) were coated with type III collagen molecules and their corresponding aminopropeptide but not with the aminopropeptide of type I procollagen. The aminopropeptide of type I procollagen was present on thin fibrils only at the epidermo-dermal junction in adult skin. Immunoblotting of skin extracts revealed the presence of both pN-type III procollagen (collagen plus the aminopropeptide) and pN-type I procollagen in fetal skin, but only pN-type III in adult skin. This study demonstrates that type I and type III collagens coexist within the same fibril and that the aminopropeptide of type III procollagen is present at the surface of type I collagen fibrils that apparently have reached full growth. PMID- 2186690 TI - Assembly of basement membranes. PMID- 2186691 TI - Transforming growth factor-beta. Major role in regulation of extracellular matrix. PMID- 2186692 TI - Merosin and laminin. Molecular relationship and role in nerve-muscle development. PMID- 2186693 TI - Laminin in neuronal development. PMID- 2186694 TI - The structure and function of type VII collagen. PMID- 2186695 TI - Mapping collagen gene mutations. PMID- 2186696 TI - Hypertrophic cartilage matrix. Type X collagen, supramolecular assembly, and calcification. PMID- 2186697 TI - Fibrillar collagen genes. Structure and expression in normal and diseased states. PMID- 2186698 TI - The structure of type XII collagen. PMID- 2186699 TI - Structure of the human type IV collagen genes. PMID- 2186700 TI - From dietary restraint to binge eating: some theoretical considerations. AB - A correlation between dietary restraint and the occurrence of binge eating has been convincingly shown in several investigations. However, the mediating mechanisms have not yet been elaborated in detail nor linked to empirical evidence. This theoretical gap is addressed in the following. After a short review of behavioral and metabolic correlates of dietary restraint, potential effects of restrained eating on the psychophysiological regulation of food intake are described. These effects may lead to the disruption of intake regulation and therefore can be regarded as direct causes of binge eating. PMID- 2186701 TI - Vanadate-stimulated oxidation of NAD(P)H in the presence of biological membranes and other sources of O2-. PMID- 2186702 TI - Insulin release in pancreatic islets by a glycolytic and a Krebs cycle intermediate: contrasting patterns of glyceraldehyde phosphate and succinate. AB - Glyceraldehyde phosphate, a glycolytic intermediate, and succinic acid (as its methyl ester to make it permeable to the cell), a citric acid cycle intermediate, were the only glucose metabolites of many recently tested that stimulated insulin release. The effects of these two "new" insulin secretagogues on several pancreatic islet parameters were compared. Glyceraldehyde phosphate stimulated all of the insulin it released during the first 5 min after islets were exposed to it, and its maximum effect on calcium uptake was observed at 5 min. Monomethyl succinate stimulated insulin release mostly during the last 30 min of a 1-h incubation and its maximum effect on calcium uptake was at 60 min after it was applied to islets. Monomethyl succinate-induced insulin release, but not glyceraldehyde phosphate-induced insulin release, was inhibited by metabolic inhibitors (antimycin A, rotenone, cyanide, FCCP, fluoride, and iodoacetamide). This is consistent with the idea that monomethyl succinate is hydrolyzed to succinate which is metabolized intramitochondrially. The effects of glyceraldehyde suggest that glucose signals the first phase of insulin release by an agonist-like mechanism that originates in the cytosol and requires minimal energy. The effects of monomethyl succinate suggest that the signal for the second phase of glucose-induced insulin release originates in the mitochondrion and requires a large amount of energy. PMID- 2186703 TI - Expression in Escherichia coli of rat liver cytosolic glutathione S-transferase Yc cDNA. AB - An expression plasmid, pKK-GTB2, containing the complete coding sequence of a rat liver glutathione S-transferase Yc subunit was constructed and expressed in Escherichia coli. The entire Yc cDNA sequence from plasmid pGTB42 (Telakowski Hopskins et al., 1985, J. Biol. Chem. 260, 5820-5825) was amplified by the polymerase chain reaction, subcloned into modified expression vector A6316 (Schoner et al., 1986, Proc. Natl. Acad. Sci. USA 83, 8506-8510 and Linemeyer et al., 1987, Bio/Technology 5, 960-965) and transformed into E. coli strain AB1899. The colonies were screened by hybridization to pGTB42 and the production of Yc subunit was detected by immunoblot analysis. The purified recombinant Yc subunit was active in the conjugation and peroxidation reactions, and appeared homogeneous as judged by sodium dodecyl sulfate gel electrophoresis. Amino acid sequencing of the expressed Yc subunit revealed that about 40% of the expressed protein was blocked at the N-terminus. Approximately 25% of the sequenceable protein (15% of total protein) contained the initiation methionine residue at the amino terminus whereas the rest of the sequenceable protein had proline as the N terminus. In contrast, only one molecular species with Pro as the first amino acid was identified when the inducer isopropyl-beta-D-thiogalactopyranoside was omitted in the growth medium. Our observation indicated that under certain growth conditions, the enzymes responsible for protein maturation were not able to complete the processing of the overproduced recombinant Yc in E. coli. PMID- 2186704 TI - Evidence that chemical modification of a positively charged residue at position 189 causes the loss of catalytic activity of iron-containing and manganese containing superoxide dismutases. AB - The Escherichia coli, Bacillus stearothermophilus, and human manganese-containing superoxide dismutases (MnSODs) and the E. coli iron-containing superoxide dismutase (FeSOD) are extensively inactivated by treatment with phenylglyoxal, an arginine-specific reagent. Arg-189, the only conserved arginine in the primary sequences of these four enzymes, is also conserved in the three additional FeSODs and five of the six additional MnSODs sequenced to date. The only exception is Saccharomyces cerevisiae MnSOD, in which it is conservatively replaced by lysine. Treatment of S. cerevisiae MnSOD with phenylglyoxal under the same conditions used for the other SODs gives very little inactivation. However, treatment with low levels of 2,4,6-trinitrobenzenesulfonate (TNBS) or acetic anhydride, two lysine-selective reagents that cause a maximum of 60-80% inactivation of the other four SODs, gives complete inactivation of the yeast enzyme. Total inactivation of yeast MnSOD with TNBS correlates with the modification of approximately five lysines per subunit, whereas six to seven acetyl groups per subunit are incorporated on complete inactivation with [14C]-acetic anhydride. It appears that the positive charge contributed by residue 189, lysine in yeast MnSOD and arginine in all other SODs, is critical for the catalytic function of MnSODs and FeSODs. PMID- 2186705 TI - Proteolytic degradation of ferredoxin-NADP reductase during purification from spinach. AB - Ferredoxin-NADP reductase (FNR) was rapidly isolated from spinach leaves with special care to suppress proteolytic degradation. The molecular mass of this FNR preparation was estimated to be 35 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Limited proteolysis of 35-kDa FNR to 33-kDa FNR was effectively suppressed by high pH (at pH 9.3), concentrated salts, and low temperature. On the basis of these observations, a new isolation procedure was designed to obtain 35-kDa FNR in a preparative scale. The resulting final preparation still contained two FNR components. One appeared to correspond to the longest polypeptide so far reported for spinach FNR (Karplus et al., 1984, Biochemistry 23, 6576-6583) while the other lacked a gamma-pyroglutamyl residue from its amino terminus. Conventional preparation procedure without suppression of proteolytic action yielded an FNR preparation with a molecular mass of 33 kDa. This FNR preparation consisted of three components. They lacked 11 to 17 amino terminal residues, while their carboxyl-terminal structure was retained intact. These results showed that proteolytic degradation of the spinach FNR molecule during purification took place exclusively at its amino-terminal moiety and further suggested that 35-kDa FNR with Karplus' structure should be the mature FNR molecule functional in the chloroplast thylakoids. PMID- 2186706 TI - Treatment of sepsis with IgG in very low birthweight infants. PMID- 2186707 TI - Ultrasound measurement of renal size in newborn infants. AB - Renal measurements were made by ultrasonography in 560 healthy newborn infants. Three dependent variables (kidney length, kidney depth, and kidney area) were measured, together with three independent variables (birth weight, head circumference, and gestational age). The SD of the measurement inconsistency was 0.13 cm for length, 0.078 cm for depth, and 0.32 cm2 for area; the percentages of total variance caused by measurement inconsistency were 7.9, 9.5, and 7.5, respectively. There was a significant difference between right and left kidneys in length and depth for each independent variable. The left kidney increased more in length and less in depth than the right so that the areas remained similar as the scale of variable increased. Kidney depth and area in boys were significantly larger than in girls, both dimensions increasing at equal rates. Centile charts for each dependent variable by each independent variable were constructed by a non-parametric method. PMID- 2186708 TI - Tuberous sclerosis presenting with fetal and neonatal cardiac tumours. AB - Cardiac tumours were identified on ultrasonography in fetal or early postnatal life in five infants. Tuberous sclerosis was subsequently diagnosed in all five. Only one infant required operation. Regression of the tumour occurred in three. No infant had hypomelanotic macules at birth, and they took up to two years to appear. PMID- 2186709 TI - Diagnosis and management of fetal growth retardation. PMID- 2186710 TI - Charles White (1728-1813) and natural birth. PMID- 2186711 TI - [Microflora in patients with complicated forms of acute cholecystitis treated by low-frequency ultrasonics and sulfacrylate glue]. AB - Investigation of microflora in patients with complicated acute cholecystitis treated with low frequency ultrasound in combination with sulfacrylate glue showed that Staphylococcus and Escherichia played the leading role in the complication etiology. Among the nonsporulating organisms bacteroides predominated. The combined use of low frequency ultrasound and sulfacrylate glue in treatment of complicated acute cholecystitis proved to be an efficient procedure providing more rapid sanation of the purulent inflammation foci. PMID- 2186712 TI - Soluble and membrane-bound ferrisiderophore reductases of Escherichia coli K-12. AB - After uptake of microbial ferrisiderophores, iron is assumed to be released by reduction. Two ferrisiderophore-reductase activities were identified in Escherichia coli K-12. They differed in cellular location, susceptibility to amytal, and competition between oxygen and ferrichrome-iron(III) reduction. The ferrisiderophore reductase associated with the 40,000 X g sediment (membrane bound enzyme) was inhibited by 10 mM amytal in contrast to the ferrisiderophore reductase present in the 100,000 X g supernatant (soluble enzyme). Reduction by the membrane-bound enzyme followed sigmoid kinetics, but was biphasic in the case of the soluble enzyme. The soluble reductase could be assigned to a protein consisting of a single polypeptide of Mr 26,000. Reduction of iron(III) by the purified enzyme depended on the addition of NADH or NADPH which were equally active reductants. The cofactor FMN and to a lesser degree FAD stimulated the reaction. Substrate specificity of the soluble reductase was low. In addition to the hydroxamate siderophores arthrobactin, schizokinen, fusigen, aerobactin, ferrichrome, ferrioxamine B, coprogen, and ferrichrome A, the iron(III) complexes of synthetic catecholates, dihydroxy benzoic acid, and dicitrate, as well as carrier-free iron(III) were accepted as substrates. Both ferrisiderophore reductases were not controlled by the fur regulatory system and were not suppressed by anaerobic growth. PMID- 2186713 TI - Effects of ethanol on Saccharomyces cerevisiae as monitored by in vivo 31P and 13C nuclear magnetic resonance. AB - Cell suspensions of a respiratory deficient mutant of Saccharomyces cerevisiae were monitored by in vivo 31P and 13C Nuclear Magnetic Resonance in order to evaluate the effect of ethanol in intracellular pH and metabolism. In the absence of an added energy source, ethanol caused acidification of the cytoplasm, as indicated by the shift to higher field of the resonance assigned to the cytoplasmic orthophosphate. Under the experimental conditions used this acidification was not a consequence of an increase in the passive influx of H+. With cells energized with glucose, a lower value for the cytoplasmic pH was also observed, when ethanol was added. Furthermore, lower levels of phosphomonoesters were detected in the presence of ethanol, indicating that an early event in glycolysis is an important target of the ethanol action. Acetic acid was identified as responsible for the acidification of the cytoplasm, in experiments where [13C]ethanol was added and formation of labeled acetic acid was detected. The intracellular and the extracellular concentrations of acetic acid were respectively, 30 mM and 2 mM when 0.5% (120 mM) [13C]ethanol was added. PMID- 2186714 TI - Oral contraceptive administration, interfemale relationships, and sexual behavior in Macaca fascicularis. AB - The effects of oral contraceptive administration on the social relationships of adult female cynomolgus monkeys (Macaca fascicularis) were examined. Ten females were administered ethinyl estradiol/ethynodiol diacetate (Demulen), 10 were administered ethinyl estradiol/norgestrel (Ovral), and 10 served as a control group. The monkeys lived in social groups of 5 females each, and patterns of social interaction and social status were recorded. Interfemale relationships were also observed when a vasectomized male was placed in each social group for 50 min, once/week. During the latter observations, preliminary data on the effects of oral contraceptive treatment on sexual interaction were also collected. In the absence of the male, interfemale agonistic interactions and time spent alone were influenced by social status but not by oral contraceptive treatment. Time spent in passive body contact, an affiliative state, was reduced by Ovral treatment. In the presence of the male, dominant females aggressively interfered with the sexual interactions of subordinates. This aggression resulted in the termination of a greater proportion of the sexual interactions of subordinates than dominants in the control group only, indicating suppression of this type of interaction by oral contraceptive treatment. Other effects included a decreased frequency of ejaculation with Ovral-treated females. These results suggest that oral contraceptives may suppress certain types of female agonistic behavior (e.g., in the context of mate competition) and some oral contraceptives may interfere with sexual activity. More broadly, these findings indicate that intrasexual competition for access to mates may occur in females as well as males. PMID- 2186715 TI - Hormonal replacement therapy for postmenopausal women: a review of sexual outcomes and related gynecologic effects. AB - The impact of hormonal replacement therapy on sexual behavior and functioning in postmenopausal women was examined. A methodological overview discusses issues of subject characteristics, research design, and the assessment of sexual functioning and related outcomes. Current therapy regimens include estrogen, progestogen, androgen, and combination therapy (e.g., cyclic estrogen and progestogen). With estrogen, significant gynecologic improvement (i.e., reduction in atrophic vaginitis) occurs, and this may in turn provide the context for sexual activity/functioning to proceed unimpaired. Although there are medical indications for the addition of progestogen to an estrogen regimen, there appear to be no improvements in sexual functioning beyond those that occur with estrogen alone. Finally, androgen may affect sexual functioning for specific subgroups of postmenopausal women (i.e., surgically postmenopausal rather than naturally postmenopausal women). PMID- 2186716 TI - Influence of acarbose (a glucosidase inhibitor) on experimental atherosclerosis in the rabbit. AB - Acarbose, a complex oligosaccharide of microbial origin, was added at levels of 100, 200 or 400 mg/kg to an atherogenic diet fed to New Zealand White rabbits. The rabbits consumed 75 g/day of each diet, thus the daily intake of Acarbose was 7.5, 15 and 30 mg. Rabbits fed 30 mg/day of Acarbose showed reduced levels of plasma cholesterol, intermediate density lipoprotein (IDL) and low density lipoprotein (LDL). Aortic sudanophilia was inhibited by 23% in rabbits fed 7.5 mg/day of Acarbose and by 43% in rabbits fed 15 or 30 mg/day. Acarbose had been shown previously to lower serum cholesterol and triglyceride levels in rats and mice. Our studies demonstrate that it also inhibits atherogenesis in rabbits fed 0.2% cholesterol. PMID- 2186718 TI - [The centenary of the German Zentralblatt fur allgemeine Pathologie und pathologische Anatomie]. PMID- 2186717 TI - [An immunohistochemical study of the localization of embryonic prealbumin in the gastric mucosa in chronic gastritis and hyperplastic polyps]. AB - The location of embryonic prealbumin (EPA) was investigated by indirect immune peroxidase test in gastric mucosa: 16 cases of chronic gastritis without malignant tumour and in 48 cases of gastric carcinoma. EPA in the mucosa was found in 35% cases of carcinoma outside the tumour and 31.3% cases of mucosa without tumour. The highest expression of EPA was found in stromal component of hyperplastic polyp without malignancy. Comparison of EPA and carcinoembryonic antigen in tissue did not reveal the presence of correlation between these oncofetal markers. Most likely this antigen is of a reactive nature and it can not be used for the evaluation of the probability of gastric mucosa malignant transformation. PMID- 2186719 TI - [Astrocytic glia in the pathogenesis of Creutzfeldt-Jakob disease]. AB - The role of astrocytes in pathogenesis of Creutzfeld-Jakob disease (CJD), one of the slow virus infections of human central nervous system caused by an unconventional virus (prion) has been studied. Histological and ultrastructural examinations of the brain of both dead people and experimentally infected guinea pigs, combined with the data on morphofunctional state of infected monolayer glial culture analysis have shown astrocytes, as well as neurons, to be target cells for the causative agent of the disease. The astrocyte changes observed were evaluated as proliferative-degenerative ones with the activation prevailing over the cell destruction. It was determined that both fibrous and protoplasmic astrocytes are sensitive to the cell-destructive effect of the CJD agent. Only few astrocytes possess phagocytic activity against the background of CNS degenerative changes in CJD. It is supposed that activated astrocytes are involved in new intercellular reactions, this involvement aggravating the pathological process. PMID- 2186720 TI - [The molecular level of general pathological processes]. AB - The knowledge of the molecular level of the general pathologic processes is a prerequisite for new concepts realized in the practice. The molecular destructive processes, programmed cell death and inflammation are considered as examples. The hypothesis of the catastrophe of errors is reviewed, the results of studies on the limited proteolysis reaction as well as intracellular destructive processes compatible with the life of cell are summarized. The concept of nonphagocytic tissue resistance and resorptive cellular resistance as a peculiar type of nonspecific protective reactions in the infectious inflammation is substantiated. PMID- 2186721 TI - [A case of seronegative systemic lupus erythematosus (an immunopathological study)]. AB - A case of systemic lupus erythematosus (SLE) in a 37-year-old female is described which was primarily diagnosed as epilepsy. Immunopathologically, an immunoglobulin in the nuclei of the majority of cells in the skin biopsy and blood cells was found against the background of the lack of SLE manifestations (antinuclear factor in the circulating blood, skin lesions, etc.). Antibodies against the antigen of vascular intima are revealed in the blood by means of the indirect immunofluorescence. The epilepsy diagnosis was established due to the prevalence of the brain vessels affection (frequent loss of consciousness). The progression of the disease with the involvement of joints, heart, lungs and other organs, high indexes of the rheumatoid factor made it necessary to differentiate between rheumatoid arthritis and SLE. The immunopathological examination confirmed the SLE diagnosis. Hemosorption combined with a standard therapy was followed by the decrease of the immunopathological manifestations. PMID- 2186722 TI - [Protein S-100 in the histological diagnosis of tumors]. AB - Review deals with the use of the antibodies against protein S-100 in the diagnosis of tumours in man and experimental animals. Protein S-100 was first isolated from the bovine brain and then identified in glial and Schwann cells of the nervous system, epidermal Langerhans cells, myoepithelial cells of the salivary and mammary glands and in many other cells of various organs. In spite of the lack of specificity to any tissue antibodies against protein S-100 are widely used in the diagnosis of human tumours, mainly for the differentiation between neurogenic and soft tissue tumours (positive response to S-100 protein is regularly observed in benign schwannomas, neurofibromas and granular cell tumours while fibroblastic tumours are S100-negative), for the differentiation between nonpigmented melanomas (positive) and anaplastic carcinomas (negative). The knowledge of S-100 protein distribution in normal organ facilitates the establishment of the tumour origin. Antibodies against S-100 protein allowed one to establish the neurogenic origin of some rat soft tissue tumours which were considered otherwise to be of mesenchymal origin and gave additional proof of the neurogenic origin of the rat endocardial tumours. PMID- 2186723 TI - Cancer from exposure to 50/60 Hz electric and magnetic fields--a major scientific debate. AB - Millions of dollars are presently being spent on both laboratory and epidemiological studies to determine if an association exists between the exposure of humans to 50/60 Hz electromagnetic fields and cancer incidence. This review discusses findings from both of these areas of study and focuses attention on their relevance to the electromagnetic field-cancer debate. So far, the conflicting results from epidemiology have succeeded only in raising the concerns of both occupationally exposed groups and the general public. A few hypotheses have suggested possible mechanisms by which fields could exert biological effects. However the studies on which these hypotheses are based require substantiation and further, there is insufficient evidence to indicate if the biological effects observed in these studies have any relevance to human health. It will be at least another three to five years before there are results from large scale human studies presently being designed or undertaken. From an objective review of existing scientific data it can only be concluded that exposure to 50/60 Hz electric and magnetic fields at levels occurring in our environment have not been established to lead to cancer in humans. Sufficient gaps in our knowledge exist however to recommend that research continue, especially in areas identified in the text. To assist the casual reader of this subject the complex issues of cancer initiation and promotion are considered. PMID- 2186724 TI - Details of the female and male pathway of the Keimbahn determined by enzyme histochemical and autoradiographic studies. AB - Autoradiographic studies and the use of enzyme histochemistry have revealed that early germ line cells (female and male PGC, oogonia, prediplotene oocytes and prospermatogonia) as well as the more advanced germ cells (diplotene oocytes, spermatogonia, spermatocytes and spermatids) show specific patterns of their DNA and RNA synthesis and their enzymatic equipment. The female and male germ lines show similar kinetics up to the arise of oocytes and T prospermatogonia (T for transitional), the final products of a first limited multiplication process of primitive gonia. In former studies we supposed that oocytes and T prospermatogonia are the first exponents of the female and male pathway of the germ line (Hilscher and Hilscher, 1989a). Recently, it could be shown--using the reverse PLM method in slides of plastic embedded material--that the first differences between female and male GC can already be stated at the end of the first proliferation wave of oogonia and multiplying prospermatogonia; that means even before the existence of oocytes and T prospermatogonia (Hilscher and Hilscher, 1989b). Oogonia and M prospermatogonia (M for multiplying) are equipped both with only one active X chromosome. While oocytes traverse the prediplotene stages of meiotic prophase T prospermatogonia prepare for a second extensive proliferation process: spermatogenesis. Oocytes in meiosis are provided with two active X chromosomes, T prospermatogonia possess only one, and the presence of the Y chromosome is not vital for them. However, the Y chromosome is required for the normal course of spermatogenesis characterized by a stock of stem cells, that are responsible for the continuous production of male gamets. The mammalian oocyte--similar as that of insects and amphibia but to a lower degree--acts as pre-embryo. PMID- 2186725 TI - Antimalarial activity of substituted anthraquinones. PMID- 2186726 TI - Executive board. Team spirit reigns. PMID- 2186727 TI - "Personal perspective" too personal? PMID- 2186728 TI - Financial support requested. PMID- 2186729 TI - So many worlds. PMID- 2186730 TI - A brief history of IALP. International Association of Logopedics and Phoniatrics. PMID- 2186731 TI - A view of the profession in South Korea. PMID- 2186732 TI - Development of speech-language-hearing services in Guam and Micronesia. AB - Even after more than two decades of service delivery by members of this profession, the availability of limited federal funds, and the applicability of federal mandates, services within the region continue to be clearly inadequate. To assure that these inadequacies do not continue indefinitely into the future requires that members of this profession respond to the challenges and overcome the existing barriers and obstacles. PMID- 2186733 TI - Soviet symposium on speech pathology. PMID- 2186734 TI - Opportunities for service in Third World countries. PMID- 2186735 TI - International service delivery. A strategic management plan. PMID- 2186736 TI - Our international responsibility. PMID- 2186737 TI - 1989 salaries of ASHA members. PMID- 2186738 TI - Medical informatics for the other ninety percent: the Dartmouth experience. PMID- 2186739 TI - A field test of the TIME patient simulation model. AB - The Technological Innovations in Medical Education (TIME) Project has created an interactive videodisc patient-simulation model that provides faculty with a new method for patient-centered teaching in the medical school classroom. The TIME model is designed to be controlled by a professor in the classroom setting, and incorporates voice recognition technology and video dramatization to create a believable patient encounter. Under the auspices of the Lister Hill National Center for Biomedical Communications, National Library of Medicine, where the Project originated in 1983, three medical schools participated in a field test of this "high-tech" model. Six faculty members made ten classroom presentations of two TIME simulations to 306 second-year medical students. The principal finding was that, in a group setting, a large majority of the students at all three schools became individually committed to the care and management of the simulated patient. They acted as if the patient's problems were real and left the session feeling as though they had interacted with an actual person. Therefore, in terms of simulating a real patient, the TIME patient-simulation model was validated, providing the basis for the development of new patient-centered methods to teach and test medical students in the classroom setting. The Project has been at the Georgetown University School of Medicine, where the model is being introduced into the existing curriculum, since 1988. It is currently being used as a part of the final examination for second-year students and in discussion-group settings for fourth-year students in the internal medicine clerkship. A field test is also under way using the TIME model to assess the clinical performance of third-year students. PMID- 2186740 TI - The availability of fellowship training for foreign family physicians. AB - The authors surveyed the 49 U.S. fellowship programs in family medicine listed in the 1988 Fellowship Directory published by the Society of Teachers of Family Medicine. The past experience and future intentions of the 47 responding programs toward non-immigrant foreign family physicians coming to the United States to undergo fellowship training in academic family practice were studied. Only a minority of the programs (22%) had ever trained a foreign fellow, and of these only five of 11 were definitely able to do so in the future. Over half (52%) of the programs that had never trained a foreign fellow stated that they were not prepared to train a foreign physician. Although foreign family physicians are encouraged by the American Academy of Family Practice to come to the United States for fellowships, this study shows that it is extremely difficult for these physicians to find programs willing to act as host. PMID- 2186741 TI - Synthesis and pharmacological screening of new angiotensin converting enzyme inhibitors. AB - We report the preparation of a series of eight L-alanyl-L-proline derivatives and four L-proline derivatives. Their pharmacological activity as antihypertensive agents was examined with reference to changes in the contractile response to angiotensin I (AI), bradykinine (BK) and angiotensin II (AII). Compounds 1g, 1h and 2c were the most powerful when compared with known angiotensin-converting inhibitors such as captopril and enalapril, and were selected for further pharmacological study. PMID- 2186742 TI - Cytokine update. PMID- 2186743 TI - Evolutionary implications of a new bypass activation pathway of the complement system. AB - The classical pathway of complement activation is a highly specific and amplifiable effector system responding to recognition of foreign antigens by antibody. It comprises a group of well characterized proteins in mammalian plasma. There are many similarities with the alternative pathway of complement activation, which suggests that they have a common evolutionary origin. Both pathways have homologous components, use related activation and regulatory mechanisms, result in the release of the anaphylatoxins C3a and C5a, and deposit C3b onto activating surfaces. This fixed C3b then becomes the focus of further immune reactions, involving either the lytic complement components or C3b receptors on effector cells. Phylogenetic data indicate that the alternative pathway is the older, and that the classical pathway evolved from it. Here Timothy Farries and colleagues review this evolutionary process and present a possible sequence of events that is suggested by recent functional data from their laboratory. PMID- 2186744 TI - Pathogenesis of the natural killer cell deficiency in AIDS. AB - Deficiency in natural killer (NK) cell activity is a common feature of acquired immune deficiency syndrome (AIDS). This is part of a general immune dysfunction in AIDS and may lead to progression of the disease, since NK cells are known to be involved in protection against tumors and against viral infections. The lack of immunological surveillance by NK cells of the growth of pathogens that activate the HIV-1 tat infectivity gene may also favor progression to AIDS. The pathogenesis of NK cell deficiency in AIDS is not known. Previous studies have shown that NK cells from AIDS patients are able to bind but not to lyse the target cell line K562. This results from an inability to rearrange the cytoskeleton microtubular (MT) system and to release the natural killer cytotoxic factor (NKCF). This report by Maria Caterina Sirianni and colleagues evaluates the possible mechanisms leading to this NK cell deficiency. PMID- 2186745 TI - The molecular basis of alloreactivity. AB - The strength of the immune response to foreign histocompatibility molecules has long puzzled immunologists. In this article Robert Lechler and colleagues propose that (1) allorecognition is structurally heterogeneous and varies according to the responder and stimulator MHC types, (2) in closely related combinations the focus of the alloreactive T cell may be on epitopes of endogenous peptides that are displayed by stimulator but not by responder MHC molecules, seen in a 'self restricted' manner, and (3) in more disparate combinations the alloresponse may be directed primarily against residues on the allogeneic MHC molecule itself. PMID- 2186746 TI - Immunological adjuvants: a role for liposomes. AB - Recent technological advances have resulted in the production of safe subunit and synthetic small peptide vaccines. These vaccines are weakly or non-immunogenic and cannot, therefore, be used effectively in the absence of immunological adjuvants (agents that can induce strong immunity to antigens). Owing to the toxicity of adjuvants, only one (aluminium salts) has hitherto been licensed for use in humans, and it is far from ideal. In this article, Gregory Gregoriadis discusses the use of liposomes as an alternative safe, versatile, universal adjuvant that can induce humoral- and cell-mediated immunity to antigens when administered parenterally or enterally. PMID- 2186747 TI - Human monocyte chemoattractant protein-1 (MCP-1). AB - During the past three years great advances have been made in the chemistry and biology of chemoattractants for human leukocytes. Two chemoattractant cytokines have been isolated, sequenced and cloned, each with distinctive leukocyte attractant specificity. Monocyte chemoattractant protein 1 (MCP-1), the subject of this review by Edward Leonard and Teizo Yoshimura, is secreted by PHA stimulated mononuclear cells and can be identified by northern blotting in response to LPS or PHA. It attracts monocytes but not neutrophils. In contrast, neutrophil attractant/activation protein (NAP-1) (also known as interleukin 8 (IL 8)) attracts and activates human neutrophils but it is not a chemoattractant for human monocytes. Based on amino acid sequence analysis, each of these attractants has been assigned to one of two distinct families of cytokines that are thought to participate in host defense and inflammatory responses. PMID- 2186748 TI - Direct intrafollicular differentiation of memory B cells into plasma cells. AB - Antibody-forming (plasma) cells and memory B cells are both generated during a humoral immune response in the spleen. Antibody-forming cells develop in the outer parts of the periarteriolar lymphocyte sheaths (PALS) while memory B cells develop in the lymphoid follicles. As soon as the first antibodies appear in the circulation, immune complexes are formed, the bulk of which are ingested by cells of the mononuclear phagocyte system. A small proportion, however, is immobilized on the processes of follicular dendritic cells (FDCs). These immune complexes are thought to play a key role in the generation of memory B cells in the follicles. In this article Nico van Rooijen postulates that, in the continuing presence of soluble antigen, the newly generated memory B cells in the follicles may continue to differentiate into antibody-forming cells. Experimentally such conditions are fulfilled when adjuvants that slowly release antigen are used and when antigens used for immunization can replicate in the body. The postulated synergistic action of immobilized immune complexes and soluble antigen in the follicles may represent an efficient mechanism for the rapid production of large numbers of plasma cells. PMID- 2186749 TI - A strategy for founding a global lymphocyte proteinpaedia and gene catalogue. AB - In this article, Ivan Lefkovits, John Kettman and Christopher Coleclough describe a strategy for a comprehensive analysis of the genes active in lymphocytes. It allows direct access to the coding sequence of any gene, provided that the two dimensional gel spot coordinate position is known. The authors have constructed representative lymphocyte cDNA libraries and partitioned them into many sectors, each containing a unique set of cDNA clones. Data from the analysis of natural lymphocyte proteins is compiled into a 'proteinpaedia', which is matched to a gene catalogue comprising the partitioned recombinant phage collection. PMID- 2186750 TI - Autoantibodies to cytokines--friends or foes? AB - Cytokines form a network of communication signals between cells of the immune system, and between the immune system and other organs. They interact with structurally complex and often dynamically expressed target cell receptors. The recent demonstration of autoantibodies to cytokines, even in sera of normal individuals, suggests further complexities in the way that nature regulates cytokine functions. Based mainly on evidence obtained by investigating autoantibodies to interleukin 1 alpha (IL-1 alpha), Klaus Bendtzen and colleagues discuss the possibility that naturally occurring antibodies may function as specific physiological carriers and regulators of cytokines. PMID- 2186751 TI - Effects of stress on the immune system. AB - Stress, distress and a variety of psychiatric illnesses, notably the affective disorders, are increasingly reported to be associated with immunosuppression. The concept that psychic distress may predispose to medical illness is centuries old but has only recently attracted the attention of the scientific community at large. Interdisciplinary collaboration has established psychoneuroimmunology, or neuroimmunomodulation, as a new field of investigation with the goal of rigorous scientific research into the elusive mind-body connection. This has resulted in the rapid accumulation of information which falls across the boundary lines of psychiatry, immunology, neurosciences and endocrinology. Here David Khansari, Anthony Murgo and Robert Faith review the effects of stress on the endocrine and central nervous systems and the interactions between these systems and the immune response after exposure to stress signals. PMID- 2186752 TI - Immunopathogenic mechanisms of HIV infection: cytokine induction of HIV expression. AB - In this paper Zeda Rosenberg and Anthony Fauci review the prevailing hypotheses on the mechanisms by which human immunodeficiency virus (HIV) progressively and relentlessly destroys immune function in infected individuals. Although HIV can directly kill CD4+ T cells in vitro, the protracted course of HIV infection in vivo suggests that other pathogenic mechanisms are also involved. As a member of the lentivirus family, HIV can remain latent within the genome of the infected cell. Activation of HIV expression from a latent or low-level state of replication is dependent, in part, on the state of activation of the host cell. As a result, activation of HIV-infected CD4+ T cells or monocyte/macrophages during normal immune responses may ultimately result in the activation of HIV expression and spread of the infection. Thus, HIV may have developed the ability to use normal immune processes to its own reproductive advantage. PMID- 2186754 TI - [Various risk factors for infantile epilepsy relapse after the end of treatment]. AB - A study was conducted at the out-patient Pediatric Neurology clinic of the Trujillo Peru Regional Teaching Hospital on 127 children with epilepsy and who were seen for the first time at the clinic. After completing two years of continuous treatment and free of any convulsions, the patients were followed and later controlled for a minimum period of two to four years. The object of the study was to correlate the frequency of relapses and risk factors which may have influenced the convulsions. Remission was seen in 70.7% of the cases while the convulsions recurred in 29.3% of the patients. The convulsions recurred during the first 24 months after treatment was completed. Relapses of epilepsy in children are directly related to the start of the convulsions at and early age to the type and severity of the episode, to the added neurological abnormalities as well as persistent paroxysmal EEG abnormalities. PMID- 2186753 TI - [Gastrointestinal manifestations of recessive dystrophic epidermolysis bullosa]. AB - The clinical charts of eight children with gastrointestinal symptomatology secondary to recessive dystrophic epidermolysis bullosa are reviewed. The most frequently found gastrointestinal lesions were esophageal stricture (6 patients), a repeated history of ampullar lesions (8 patients), constipation (5) and anchiloglossia (2). The most frequent and feared lesion is the esophageal stricture. Esophageal stricture; epidermolysis; gastrointestinal manifestations. PMID- 2186755 TI - [Embryologic and anatomic considerations on normal and pathologic heart separation. II. Atrioventricular and interventricular septum]. AB - The atrioventricular septum is defined and its anatomical features are described. This consists of two regions, a muscular and a membranous region. Isolated atrioventricular types of defect are described. The normal and the pathological embryogenesis of the atrioventricular septum are discussed. A definition of the interventricular septum is given and its anatomical features are described. This septum is divided into two regions, a membranous and muscular region. The muscular region is divided into three regions: inflow region or inlet, trabeculated region and outflow region or outlet. Interventricular defects are classified according to the septal regions in which they are located. The anatomical features which characterize each type of interventricular septal defect are established. A brief comment on the normal and pathological morphogenesis of the interventricular septum is made. PMID- 2186756 TI - [Ambulatory aerosol therapy in children with bronchial obstruction and hyperreactivity]. AB - Some of the main objectives for the use of aerosol therapy in the treatment of bronchial obstruction are pointed out. This has all been possible due to the physical findings on the use of aerosols, their mode of action, the size and speed of the particles, the level of bronchial obstruction ventilation and the technique behind it all. The main advancements in the treatment of asthma are described according to the degree of severity. Special attention is given to the great impact caused by the management of childhood lung obstruction. Bronchial obstruction; aerosol therapy; bronchial hyperreactivity. PMID- 2186757 TI - [Oral rehydration at a third-level service]. AB - Oral rehydration therapy (ORT) has been shown to be useful in decreasing mortality, reducing treatment costs and diminishing the frequency of complications in children under the age of five with acute diarrhea. The current concept of ORT includes not only the increase in the intake of fluids and the administering of oral solution in order to prevent or treat dehydration, but also the continuance of everyday feeding, the teaching of the child's mother to detect signs of dehydration and other alarming changes, as well as the non-administering of medication, especially those considered as anti-diarrheal or anti-vomiting, and limiting the use of antimicrobials, only to be used in special cases. The theoretical know-how of these concepts has been seen to be insufficient in order to increase the use of community-wide Oral Rehydration Therapy, being this the main purpose for the establishment of the Oral Rehydration Ward in teaching hospitals of second and third level, where the majority of its' personnel must come into contact with and share the responsibility of treating children with diarrhea. Within these wards students obtain information, ability and assurance in the effective actual management of children with diarrhea, including the correction of the state of dehydration through the administering of oral solutions. Another complementary benefit from the coming about of this ward is the decrease in the need to hospitalize the majority of the patient with diarrhea therefore reducing costs and any related complications. Oral rehydration therapy; diarrhea; dehydration; oral solutions. PMID- 2186758 TI - The relationship between metabolite production and the growth efficiency of the producing organism. PMID- 2186759 TI - Dynamics of microbial growth and cell composition in batch culture. PMID- 2186760 TI - Mechanisms of iron acquisition and bacterial virulence. PMID- 2186761 TI - [Malignant nasosinusal melanoma: apropos of a case]. AB - We present a case of a nasosinusal malignant melanoma with a really fulminant evolution, as the patient died two and a half months after the diagnostic biopsy and five months after the initial symptoms. A bibliographic review of these rare tumours is realized, and those data of the world literature we could reach concerning to incidence, clinic features, histopathology, diagnosis, treatment, and prognosis, are analyzed. PMID- 2186762 TI - Human B and T lymphocyte responses to vaccination with pneumococcal polysaccharides. PMID- 2186763 TI - [Cerebral circulation and calcium antagonists]. PMID- 2186764 TI - [Ca antagonists in neurosurgical practice]. PMID- 2186765 TI - [Transient hypoglycemic hemiplegia due to insulin autoimmune syndrome--a case report]. AB - Hypoglycemia causes a variety of neurologic symptoms, and yet it is rarely responsible for such a sudden, focal neurologic deficit as hemiplegia. Herein we described a rare case of what was believed to be transient hypoglycemic hemiplegia. An 80-year-old woman was admitted to the hospital on June 10, 1988, following frequent episodes of abnormal behavior and transient weakness of the right extremities. These symptoms, similar to those of cerebrovascular diseases, characteristically occurred early in the morning and disappeared after breakfast. On admission no definite abnormalities were disclosed on neurologic examination. Neuroradiological evaluations by CT, cerebral angiography and single photon emission CT failed to demonstrate abnormalities. The patient remained stable until the following morning, when she suddenly became restless and confused and developed total aphasia and the right hemiplegia. The blood sugar was estimated to be 34 mg/dl and electroencephalogram (EEG) showed continuous slow wave activities involving the bilateral fronto-parietal region. Intravenous injection of glucose solution instantaneously resulted in disappearance of both neurologic symptoms and EEG abnormality. Serum insulin level was found extremely increased ranging from 7000 to 8000 microU, eventually leading to a diagnosis of insulin autoimmune syndrome. Hemiplegia due to hypoglycemic attack was reviewed in the literature, and the pathogenesis and EEG findings were also discussed. PMID- 2186766 TI - Balloon dilatation of the aortic valve in adults: a surgeon's view. PMID- 2186767 TI - Balloon dilatation of the aortic valve in adults: a physician's view. PMID- 2186768 TI - Haemodynamic changes caused by alteration of autonomic activity in patients with heart failure. AB - In 14 patients with heart failure (New York Heart Association class 2-3) and sinus rhythm the carotid sinus baroreceptors were stimulated to induce a reflex mediated decrease of sympathetic efferent activity and a simultaneous increase in vagal tone. Five patients were in severe heart failure (New York Heart Association class 3) with raised plasma concentrations of noradrenaline at rest (2.99 (0.86) nmol/l (mean (SD)) and nine patients had less severe heart failure (class 2.2 (0.2)) and normal plasma concentrations of noradrenaline at rest. The haemodynamic responses during arterial baroreceptor stimulation were different in both groups. In all five patients with severe heart failure cardiac output increased whereas in the nine patients with less severe heart failure it was unchanged or decreased. The increase of cardiac output in the group with severe heart failure was solely the result of a significant increase of stroke volume index (by 9 (2) ml/m2). In the nine patients with less severe heart failure stroke volume remained unchanged but heart rate decreased significantly by 7 (2) beats/min during baroreceptor stimulation. These data show that an integrated change of autonomic activity consisting of a decrease in sympathetic tone and an increase in vagal activity leads to an increase of stroke volume in patients with severe heart failure and hence to haemodynamic improvement. PMID- 2186769 TI - Reduction of factor VII coagulant activity (VIIC), a risk factor for ischaemic heart disease, by fixed dose warfarin: a double blind crossover study. AB - An increase in factor VII coagulant activity is known to be an important risk factor for ischaemic heart disease. Four hundred and eight healthy male Post Office workers were screened in an occupational survey. Sixty eight (16.5%) of these had values of factor VII coagulant activity greater than 1.0 SD above the age related mean. A randomised double-blind crossover study was undertaken to investigate the effect of a fixed daily minidose of warfarin (1 mg) on the high activities of factor VII in these men. Forty two agreed to enter the study and 40 completed it. Their mean factor VII coagulant activity before warfarin treatment was 135.9%. Treatment with a fixed minidose of warfarin significantly reduced factor VII coagulant activity to 124.6%; there was no change on placebo. The prothrombin time was also significantly prolonged on active treatment although all the results remained within the normal range. These findings suggested a fixed minidose warfarin regime might be useful in the primary prevention of ischaemic heart disease by reducing high activities of factor VII. PMID- 2186770 TI - Hypercalcaemia--new mechanisms for old observations. PMID- 2186771 TI - Has chemotherapy proved itself in head and neck cancer? PMID- 2186772 TI - Adjuvant chemotherapy for early breast cancer. PMID- 2186773 TI - Insulin-tumour interrelationship in EL4 lymphoma or thymoma-bearing mice. I. Alloxan-diabetic or non-diabetic mice. AB - A study has been carried out in which a comparison was made between EL4 lymphoma (assumed to be an insulin-producing secreting tumour) and thymoma (an insulin dependent tumour). Tumour development and incidence, 3H-thymidine incorporation and insulin content in tumours, the host's food intake, blood insulin, glucose and cholesterol were determined in non-diabetic and alloxan-diabetic mice. Whereas no significant differences were observed between the diabetic and non diabetic EL4 tumour-bearing mice, the diabetic, thymoma tumour-bearing mice showed reduced tumour growth and lower tumour incidence as compared with their non-diabetic counterparts. Insulin administration to diabetic tumour bearing mice, enhanced 3H-thymidine incorporation in the thymoma tumour cells only, and the insulin content of the EL4 tumours was found to be higher than that of the thymoma tumours. Rapid diabetes remission was observed in the diabetic, EL4 tumour-bearing mice as compared with the thymoma tumour-bearing mice. PMID- 2186774 TI - Western blot analysis of the antigen in pemphigoid gestationis. AB - Using an immunoblotting technique, sera from 25 patients with pemphigoid gestationis were examined and tested against epidermal and dermal extracts of normal skin. The major antigen recognized by seven patients' sera was a molecule of 180 kDa, pemphigoid gestationis antigen, extractable only from the epidermis. Sera from 18 patients with bullous pemphigoid were studied as positive controls and the major antigen recognized was a larger molecule of 220 kDa. There was some degree of shared recognition of antigens with three patients with pemphigoid gestationis recognizing the 220 kDa bullous pemphigoid antigen. In addition one bullous pemphigoid serum recognized the 180 kDa pemphigoid gestationis antigen. The dominant pemphigoid gestationis antigen, however, differs from bullous pemphigoid antigen. PMID- 2186775 TI - Dose-response relationships for topically applied antigens. AB - Patch-test responses to serially diluted nickel sulphate and potassium dichromate solutions in patients with nickel and chrome sensitivity were assessed by pulsed A-scan ultrasound to determine skin thickness and laser-Doppler flowmeter techniques to evaluate blood flow, as well as clinical scoring. There was a relationship between the dose of antigen and the test responses as measured by ultrasound and laser-Doppler flowmeter techniques in both nickel and chrome sensitive patients. Our data suggest that both techniques may be useful in the detection of allergic contact dermatitis in which there is a doubtful patch-test reaction as well as in experimental sensitization studies. PMID- 2186776 TI - Failure of papaverine to reduce pruritus in atopic dermatitis: a double-blind, placebo-controlled cross-over study. AB - Papaverine has been reported, largely on the basis of clinical experience, to reduce the severity of pruritus associated with atopic dermatitis. A double blind, placebo-controlled, cross-over study was performed to assess the degree of improvement. Fifty subjects with atopic dermatitis each received papaverine 100 mg q.d.s. orally for 4 weeks and another 4 weeks of matching placebo in randomized order. The parameters used to measure response were pruritus as assessed on visual analogue scales by the subjects, clinical scoring of extent and severity of the dermatitis and rate of usage of topical steroid preparations. Forty-five subjects completed the protocol and no improvement in any parameter was demonstrated. PMID- 2186777 TI - Clinical features of ageing skin. AB - Ageing of the skin involves the intrinsic process of senescence and extrinsic damage induced by chronic exposure to UV radiation. A recent consensus forum of the American Academy of Dermatology concluded that the majority of undesirable clinical features associated with 'skin ageing' are the result of damage to skin due to UV radiation (photoageing). Clinically photoageing is characterized by coarseness, wrinkling, mottled pigmentation, laxity, telangiectasia, and premalignant and malignant neoplasms. The role of genetics, hormones and diet needs to be clarified. Appropriate lifelong use of sunscreens may minimize many of the changes associated with photoageing. PMID- 2186778 TI - Senescence and sunscreens. AB - The most reliable way to reduce the chronic effects of solar UV radiation is to limit exposure. Animal data using hairless albino mice suggest that the routine use of sunscreens, which usually act as UVB (280-315 nm) filters, may prevent or inhibit skin photocarcinogenesis and photoageing in man. Conditions of chronic use of sunscreens in human skin, however, are not established but it is possible that, under some circumstances, sunscreen use could enhance skin cancer risk. The use of sunscreens may prevent or inhibit both sun-induced cancers and photoageing, but as yet there is no established method of designating the efficacies of sunscreens for the prevention of the chronic effects of solar UV radiation. This is an important research objective. PMID- 2186779 TI - Sunlight-induced cancer: some new aspects and implications of the xeroderma pigmentosum model. AB - Symptoms of xeroderma pigmentosum, a hereditary disease characterized by accelerated light-induced ageing of the skin, are due to deficiencies in the repair of damaged DNA. Following UV irradiation a high incidence of thioguanine resistant mutations have been observed, which may be a model for the abnormally high incidence of freckling and benign and malignant transformation observed in these patients. Cells from patients with Cockayne's syndrome and trichothiodystrophy have also been shown to be hypermutable by UV radiation with a similar DNA repair defect, but unlike xeroderma pigmentosum patients they do not experience a higher incidence of skin cancer or freckling. An immunological defect may be a further crucial factor determining the dermatological symptoms of xeroderma pigmentosum patients. Much can be learned about the way normal individuals function from a study of aberrant functioning of individuals with defined genetic deficiencies. In the field of senescence of the skin, the disease xeroderma pigmentosum (XP) has been of particular value, as the exposed skin of these sun-sensitive individuals shows at an early age many of the features of aged sun-exposed skin of normal individuals. These features of XP skin include hyperkeratosis, freckling, benign lesions and malignant tumours, including melanomas. A full discussion of this syndrome has been given by Kraemer et al. PMID- 2186780 TI - Physiological changes in ageing skin. AB - The principal functions of the skin include protection, excretion, secretion, absorption, thermoregulation, pigmentogenesis, accumulation, sensory perception and regulation of immunological processes. These functions are all affected by the structural changes in the skin with ageing and, after middle age, most functions are reduced, some by as much as 50-60%. The physiological changes associated with these reductions include impairment of the barrier function, decreased turnover of epidermal cells, reduced numbers of keratinocytes and fibroblasts, and a reduced vascular network particularly around hair bulbs and glands. These changes result in fibrosis and atrophy, and decreases in hair and nail growth, vitamin D synthesis and the density of Langerhans cells. Production of epidermal thymocyte-activating factor, which enhances the T-cell response, is reduced leading to a decrease in the immune response; there is also a decreased functioning of Meissner's and Pacinian corpuscles. An increased generation of free radicals is observed. Certain environmental factors, particularly exposure to sun, accelerate the ageing of skin and are important in cutaneous carcinogenesis. PMID- 2186781 TI - Pigmentary changes of the ageing skin. AB - In subjects older than 25-30 years the number of enzymatically active melanocytes detectable by the dopa reaction decreases by about 10-20% per decade, with exposed skin having approximately twice as many pigment cells as unexposed skin. Chronic exposure to sunlight may stimulate the epidermal melanocyte system rather than accelerating chronological ageing. The number of melanocytic naevi declines with age. Despite the decreased melanocyte density, photoaged skin has irregular pigmentation and, frequently, there is hyperpigmentation. This may be due to greater positivity of dopa of chronically irradiated melanocytes. Heterogeneity in skin colour in exposed areas of skin is due to uneven distribution of pigment cells, a local loss of melanocytes, and a modification in the interactions between melanocytes and keratinocytes. The most common pigmented lesions in sun exposed skin include ephelides, actinic lentigo, pigmented solar keratoses and seborrhoeic keratoses, and lentigo maligna. The white spots in aged skin are usually stellate pseudoscars or idiopathic guttate hypomelanosis. Greying of the hair is due to progressive loss of melanocytes from the hair follicles. In vivo and in vitro studies are necessary to increase overall understanding of the processes involved and to improve treatment of the pigmentary changes in ageing skin. PMID- 2186782 TI - Photosensitivity in the elderly. AB - Photosensitivity to drugs and chemicals in the elderly is more prevalent due to more frequent use of medications. Phototoxic reactions to common, orally administered drugs such as diuretics, cardiac agents and antidiabetics may occur and the reactions may be remedied by discontinuing drug therapy. Photocontact dermatitis due to the ingredients in sunscreens or other agents, such as perfumes, may also arise. Diagnosis is often confirmed by photopatch testing and subsequent avoidance of these agents leads to gradual resolution. Idiopathic photodermatoses, such as sunlight-induced polymorphic light eruption or solar urticaria, may occur and persist from an early age and, in elderly subjects, they can cause mild to marked disability. The most disturbing disorder of this type is the severe, widespread eczematous chronic actinic dermatitis, which can be difficult to diagnose. Porphyrias, such as variegate porphyria or erythropoietic protoporphyria, may persist from an early age, whereas porphyria cutanea tarda generally begins in later life. Porphyrias all have specific clinical and biochemical features and, apart from variegate porphyria, usually respond well to treatment following diagnosis. Exposure of elderly skin to sunlight may also cause deterioration of many ordinary dermatoses, particularly seborrhoeic eczema, which generally respond to protection from UV exposure and to treatment of the underlying abnormality. Progress in identifying the underlying causes, the availability of increasingly sophisticated diagnostic techniques, and improvements in sunscreen preparations and therapeutic medications will probably significantly reduce abnormal photosensitivity in the elderly in the near future. PMID- 2186783 TI - The skin surface and stratum corneum. AB - In senescence, marked changes occur on the surface of the skin and in the stratum corneum. One of the most important features is the reduced quantity of hydrolipid emulsion on the skin surface. This has to be taken into account when developing skin care for the elderly. In photoaged skin especially, tretinoin ameliorates the morphological, biochemical and functional state of the skin surface and of the stratum corneum. PMID- 2186784 TI - Senescence in the skin. AB - No difference was found between groups of senescent subjects and younger adults in the control of skin temperature, heat radiation and transcutaneous oxygen pressure. Although capillary numbers decline in elderly skin, transcutaneous oxygen pressure at 43 degrees C in elderly skin is no lower than in young subjects. Topical tretinoin (0.05%) increases heat radiation from the skin, but there is no correlation with an improvement in superficial wrinkles. No conclusion is possible regarding the effects of topical tretinoin on transcutaneous oxygen diffusion due to a wide variability in results; sometimes it is increased and sometimes it is decreased. In different regions of the skin, such as the face and thigh, increased skin radiation and skin contact temperature are not associated with increased transcutaneous oxygen diffusion. PMID- 2186785 TI - Solar keratoses. AB - Solar keratoses are premalignant epidermal lesions that rarely transform to squamous cell carcinoma and occur even in temperate European climates much more frequently than has been previously supposed. Some lesions of solar keratosis may spontaneously regress due to immune rejection, but immunological influences do not appear to be responsible for keeping them from progressing to frank malignancy. Their frequency, accessibility and various morphological forms provide the basis of excellent models for carcinogenesis. PMID- 2186786 TI - The ageing dermis: the main cause for the appearance of 'old' skin. AB - Ageing of the skin is associated with progressive atrophy of the dermis, as well as changes in the architectural organization, leading to folds and wrinkles. As the dermis comprises living tissue, dermal changes are not simply the sum of age related changes occurring in the mesenchymal cells and the supporting macromolecular structures. Chronological ageing reduces the life of fibroblasts in vitro and, to some extent, in vivo; their potential for division being lower in the elderly. Fibroblasts replicate in vitro but only divide very slowly in vivo. Both endogenous factors, e.g. nutritional and endocrine status, and environmental factors, e.g. UV radiation, toxic compounds or free radicals, affect the functions of fibroblasts and the physical and chemical nature of the supporting macromolecules. Mechanical forces also play an important role in the architectural deterioration of the dermis. In vitro models have been developed using dermal cells and supporting tissue to investigate the factors involved in the ageing process. PMID- 2186787 TI - The senile epidermis: environmental influences on skin ageing and cutaneous carcinogenesis. AB - There is a wealth of new knowledge regarding mechanisms of carcinogenesis and their interaction with senescence and environmental insults, particularly on the effects of UV irradiation on the skin. Innovations and advances in tissue culture techniques now permit in vitro studies of keratinocytes and other benign and malignant skin-derived cells. The ageing processes and cutaneous neoplasia, therefore, can now be studied at the cellular level. New insights regarding the interrelationship of ageing, environment and cutaneous neoplasia are close at hand. Depletion in the number of Langerhans cells and suppression of their function in ageing and UV-exposed skin may allow tumour cells to overcome the host's defence system. The potential increase in UV irradiation due to depletion of the ozone layer may increase the incidence of skin tumours. Carcinogenesis involves three distinct steps: initiation, promotion, and malignant conversion. The mechanism has been studied in mice, where it is suggested the c-ras oncogene may play an important role. PMID- 2186788 TI - Structural changes in ageing skin. AB - As average life expectancy is increasing, the ageing of skin presents a growing problem for dermatologists. When considering ageing it is important to distinguish between the effects of true biological ageing and environmental factors, such as exposure to sun. Epidermal changes associated with ageing involve the flattening of its underside, a reduction in the number of Langerhans cells and of melanocytes, and a decline in the number of melanosomes synthesized, leading to reduced pigmentation. Dermal changes involve a reduction in the collagenous and elastic fibres, fibroblasts, mast cells and macrophages, and dilation of the lymphatic channels. The number of hair follicles declines with age, but their structure remains unchanged. Ageing does not affect the sebaceous glands, but some changes occur in the exocrine sweat glands. PMID- 2186789 TI - Some special skin tumours in the elderly. AB - A review of uncommon skin tumours, all of which characteristically arise in elderly patients, is presented. Angiosarcoma of the face and scalp is a highly progressive tumour with a poor prognosis, but initially it may be misdiagnosed as a simple bruise or cellulitis. In well-differentiated tumours a characteristic feature is interlacing endothelial cell-lined channels showing considerable nuclear atypia. Merkel cell tumours, which develop as deep-seated nodules in the skin, occur most frequently in photodamaged areas, especially on the head and neck. The prognosis of Merkel cell tumours is generally poor; histological evidence suggests that some of these tumours may be a special type of poorly differentiated squamous cell carcinoma. Atypical fibroxanthoma, which is normally benign, occurs most frequently in elderly, fair-skinned males, especially around the face. It is typically a polypoid lesion with a vascular appearance. Acantholytic squamous cell carcinomas, also known as adenoid squamous cell carcinomas, are most common in fair-skinned men with a history of keratoses. They also occur in the female genital region and the oral mucosa. Histologically, these tumours differ from squamous cell carcinomas because of their tendency to form duct-like areas in tumour lobules. PMID- 2186790 TI - Tretinoin therapy in photoageing: historical perspective. AB - Tretinoin was shown in the late 1960s to be useful for the treatment of disorders associated with abnormal epithelial differentiation; however, because of irritation, retinoids were only slowly accepted. In the 1970s, evidence accumulated to show that topical tretinoin could modulate many of the abnormalities in the epidermis and dermis associated with photoageing. It has been shown in hairless mice that tretinoin can reverse dermal elastosis with the formation of new collagen and this has led to clinical trials being carried out in man. Randomized, controlled trials have shown that topical tretinoin is effective in the treatment of photoaged skin. PMID- 2186791 TI - Topical tretinoin: its use in daily practice to reverse photoageing. AB - The effect of 0.1% tretinoin cream for the treatment of photoageing was studied in a double-blind, placebo-controlled trial. All patients applied tretinoin cream to one forearm and the vehicle cream to the other, and half of the patients also applied tretinoin cream to the face and the other half used the vehicle cream. Tretinoin treatment produced an improvement in the signs of extrinsic ageing compared with the vehicle-treated areas. Fine wrinkling was improved most, although coarse wrinkling, brown spots, tactile roughness and overall skin colour also showed clear improvement. The majority of lentigines and sun-induced freckles showed some reduction in coloration with extended treatment. It is important when using tretinoin that the treatment procedure is carefully explained to the patients and that they are warned about a retinoid reaction. It should be stressed that improvement is gradual and that regular application of the cream must continue even after improvement has been achieved. Patients should be assured that there is no evidence of carcinogenicity in humans. Although no teratogenic effects of tretinoin have been reported when applied topically, it is not advisable to use the cream when trying to conceive or when pregnant. PMID- 2186792 TI - Studies on the effects of topical retinoic acid on photoageing. AB - Tretinoin has been previously shown in animal and clinical studies to stimulate epidermal cell production and to be effective in the treatment of solar keratoses. A double-blind, placebo-controlled study confirmed that topical tretinoin produced an overall improvement in photoaged skin and decreased solar keratoses. There is no evidence that tretinoin has an irritative effect, nor is there any evidence that the improvement in appearance is due to oedema. PMID- 2186793 TI - The treatment of visible signs of senescence: the Italian experience. AB - An open clinical study was undertaken to evaluate the anti-photoageing efficacy of topical tretinoin. A length of cream of approximately 1 cm was applied to the face daily in the evening for 6 months: during month 1 of therapy 0.01% tretinoin cream was administered; 0.025% was given during month 2; and 0.05% was given in months 3-6. The clinical symptoms of photoageing (coarse wrinkling, fine wrinkling, skin thinning, mottled hyperpigmentation, laxity and xerosis) were evaluated before and after therapy. A total of 19.1% of patients withdrew from the study; only 5.6% were for treatment-related reasons. At the end of the treatment period all the clinical parameters, except xerosis, were improved. The amount of improvement varied, but only 4.2% of patients failed to show any improvement. Tolerability was excellent in 51.4% of patients, good in 44.4% and fair in 4.2%, and compliance was excellent in 47.0% of patients, good in 48.5% and fair in 4.5%. Tolerability and compliance were improved by applying the same amount of cream each day but increasing the concentration of tretinoin over the 6 month period. Silicone skin replicas of the same area of skin taken before and after treatment, analysed by scanning electron microscopy, profilometry and computer image analysis, showed a decrease in the width of wrinkles, and an improvement in skin texture and follicle density. PMID- 2186794 TI - A computerised diagnostic index for medical and neuro-ophthalmology. AB - We have developed a classification that meets the requirements of the Medical Eye Unit and computerised it. The classification uses three categories: anatomical site of lesion, pathological process, and clinical diagnosis. Each patient is identified by standard data and up to three entries in each of anatomical localisation, pathological diagnosis, and clinical diagnosis. This system allows the formation of groups of patients which can be either very specific or very broad by appropriate combination of selection criteria in the different categories. No codes are used but computer validation ensures consistent nomenclature. Computerisation allows rapid searching of records even with multiple selection criteria. The program is simple to use and validates data entries. An additional benefit is that it facilitates medical audit of the department's work. PMID- 2186796 TI - New light on visual pigment genes. PMID- 2186795 TI - Brightness discrimination and contrast sensitivity in chronic glaucoma--a clinical study. AB - The visual acuity, the difference in sensitivity of the two eyes to light (brightness ratio), and contrast sensitivity were assessed in 28 patients with chronic open angle glaucoma and compared with those of 41 normal controls of similar ages and visual acuity. The results obtained were related to the results of Tubingen visual field analysis in patients with glaucoma. Twenty-four of the 28 glaucoma patients (86%) had a significant disparity in brightness ratio between the two eyes. This was found to match the frequency of visual field loss. Moreover, there was a significant relationship between the interocular differences in brightness sense and the difference in the degree of visual field loss between the two eyes. Of the glaucoma patients 39% had sum contrast sensitivities outside the normal range for age-matched normal controls. No significant correlation was found between the interocular difference in brightness sense and the visual acuity or the interocular difference in sum contrast sensitivity. It is concluded that, in the presence of a normal visual acuity, the brightness ratio test warrants evaluation as a potential screening test for chronic open angle glaucoma. PMID- 2186797 TI - Optimal surface for impression cytology. PMID- 2186798 TI - Rhabdomyosarcoma, presenting as a facial swelling in a child. A case report and review of the literature. AB - A case of the very rare rhabdomyosarcoma as the more common second primary in a young child who had been treated for bilateral, genetic retinoblastoma is described and the importance early diagnosis emphasised. A review of the literature is presented with special reference to the prognosis of head and neck rhabdomyosarcoma and the various treatment alternatives, related to both new primary and secondary tumours in children with retinoblastoma. PMID- 2186799 TI - Spontaneous regeneration of the mandibular bone following hemimandibulectomy. AB - Spontaneous regeneration of the mandible following hemimandibulectomy is rarely reported. The main source of osteogenesis seems to be the periosteum. The critical elements being a pre-existing chronic infection and the age of the patient with immobilisation playing an insignificant role. This paper reports such a regeneration following hemimandibular resection for osteomyelitis and reviews the relevant literature. PMID- 2186800 TI - Resin-bonded arch bars. AB - A technique for constructing acid etched arch bars is described, this technique provides appropriate location of osteotomy segments in the absence of orthodontic brackets. The arch bars can be applied preoperatively with a subsequent economy of operating theatre time. PMID- 2186801 TI - Juxtacortical osteosarcoma of the jaws. AB - Osteosarcoma is a highly malignant tumour which despite modern surgery and chemotherapy still retains a relatively poor prognosis. This prognosis is, however, much better in the rare variant known as juxtacortical osteosarcoma. Both types of osteosarcoma mainly affect the long bones but the juxtacortical variant may be treated less aggressively and has a much better survival rate. The authors report four cases of juxtacortical osteosarcoma affecting the jaws and discuss these unusual tumours and their management. PMID- 2186802 TI - Does bupivacaine irrigation of third molar sockets reduce postoperative pain? A double blind controlled trial. AB - A double blind controlled randomised trial suggested that irrigation of third molar sockets with bupivacaine 0.75% produces significant reduction in pain scored on the first post-operative morning (p less than 0.01). However, this technique produces no significant reduction in opiate or oral analgesic consumption. PMID- 2186803 TI - The DNA binding domain of GAL4 forms a binuclear metal ion complex. AB - The transcription factor GAL4 from Saccharomyces cerevisiae requires Zn(II) or Cd(II) for specific recognition of the UASG sequence (Pan & Coleman, 1989). An N terminal fragment consisting of the first 63 amino acid residues of GAL4 [GAL4(63)] has been obtained by partial tryptic proteolysis of a cloned and overproduced N-terminal domain of 149 residues, GAL(149). We show that GAL4(63) contains the minimal GAL4 DNA binding domain. GAL4(63) binds tightly 1-2 mol of Zn(II) or 2 mol of Cd(II). 113Cd NMR of 113Cd(II)-substituted GAL4(63) reveals structural identity between the metal binding domains of GAL4(63) and that of the larger precursor GAL4(149). 113Cd(II) can be substituted for the Zn(II) in GAL4(63), and two 113Cd NMR signals are observed at 706 and 669 ppm, both suggesting coordination of 113Cd(II) to three or four -S- ligands. With the exception of the N-terminal methionine, the only sulfur-containing residues are the six highly conserved cysteines. High-resolution 1H NMR of Zn(II)-GAL4(63) and Cd(II)-GAL4(63) show the two proteins to have almost identical conformations and to be present as monomers in solutions up to millimolar concentration. This leads us to postulate that GAL4 does not possess a TFIIIA-like "Zn-finger" but forms a binuclear metal cluster involving all six cysteines in a "cloverleaf"-like array. GAL4(63) contains about 60% alpha-helix, estimated from circular dichroism. Removal of the native Zn(II) causes substantial unfolding of the secondary structure. Unlike GAL4(149), the resultant apoprotein is not induced to refold by readdition of Zn(II) at low concentrations. PMID- 2186804 TI - Complete sequence-specific 1H NMR assignments for human insulin. AB - Solvent conditions where human insulin could be studied by high-resolution NMR were determined. Both low pH and addition of acetonitrile were required to overcome the protein's self-association and to obtain useful spectra. Two hundred eighty-six 1H resonances were located and assigned to specific sites on the protein by using two-dimensional NMR methods. The presence and position of numerous dNN sequential NOE's indicate that the insulin conformation seen in crystallographic studies is largely retained under these solution conditions. Slowly exchanging protons were observed for seven backbone amide protons and were assigned to positions A15 and A16 and to positions B15-B19. These amides all occur within helical regions of the protein [Chawdhury, S.A., Dodson, E.J., Dodson, G.G., Reynolds, C.D., Tolley, S.P., Blundell, T.L., Cleasby, A., Pitts, J.E., Tickle, I.J., & Wood, S.P. (1983) Diabetologia 25, 460-464]. PMID- 2186805 TI - P+QA- and P+QB- charge recombinations in Rhodopseudomonas viridis chromatophores and in reaction centers reconstituted in phosphatidylcholine liposomes. Existence of two conformational states of the reaction centers and effects of pH and o phenanthroline. AB - The P+QA- and P+QB- charge recombination decay kinetics were studied in reaction centers from Rhodopseudomonas viridis reconstituted in phosphatidylcholine bilayer vesicles (proteoliposomes) and in chromatophores. P represents the primary electron donor, a dimer of bacteriochlorophyll; QA and QB are the primary and secondary stable quinone electron acceptors, respectively. In agreement with recent findings for reaction centers isolated in detergent [Sebban, P., & Wraight, C.A. (1989) Biochim. Biophys. Acta 974, 54-65] the P+QA- decay kinetics were biphasic (kfast and kslow). Arrhenius plots of the kinetics were linear, in agreement with the hypothesis of a thermally activated process (probably via P+I ; I is the first electron acceptor, a bacteriopheophytin) for the P+QA- charge recombination. Similar activation free energies (delta G) for this process were found in chromatophores and in proteoliposomes. Significant pH dependences of kfast and kslow were observed in chromtophores and in proteoliposomes. In the pH range 5.5-11, the pH titration curves of kfast and kslow were interpreted in terms of the existence of three protonable groups, situated between I- and QA-, which modulate the free energy difference between P+I- and P+QA-. In proteoliposomes, a marked effect of o-phenanthroline was observed on two of the three pKs, shifting one of them by more than 2 pH units. On the basis of recent structural data, we suggest a possible interpretation for this effect, which is much smaller in Rhodobacter sphaeroides. The decay kinetics of P+QB- were also biphasic. Marked pH dependences of the rate constants and of the relative proportions of both phases were also detected for these decays. The major conclusion of this work comes from the biphasicity of the P+QB- decay kinetics. We had suggested previously that biphasicity of the P+QA- charge recombination in Rps. viridis comes from nonequilibrium between protonation states of the reaction centers due to comparable rates of the protonation events and charge recombination. This hypothesis does not hold since the P+QB- decays occur on a time scale (tau approximately 300 ms at pH 8) much longer than protonation events. This leads to the conclusion that kfast and kslow (for both P+QA- and P+QB-) are related to conformational states of the reaction centers, existing before the flash. In addition, the fast and slow decays of P+QB- are related to those measured for P+QA-, via the calculations of the QA-QB in equilibrium QAQB- apparent equilibrium constants, K2.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2186806 TI - Folding kinetics of phage T4 thioredoxin. AB - The folding mechanism for bacteriophage T4 thioredoxin is best described by a four-state box mechanism, N----Uc----Ut----It----N, where N indicates native, Uc the unfolded form with the cis proline isomer, Ut unfolded with the trans proline isomer, and It a compact form with a trans proline isomer. Both manual mixing fluorescence and size-exclusion chromatography indicate that there is a cis-trans proline isomerization that is important to the folding pathway. Furthermore, the data suggest that the cis-trans isomerization can also occur in a compact nativelike state which is referred to as It. The slow phase seen in fluorescence seems to be monitoring the cis-trans isomerization in the compact form, not the isomerization which occurs in the denatured state. PMID- 2186807 TI - Substrate specificity of recombinant human renal renin: effect of histidine in the P2 subsite on pH dependence. AB - Steady-state kinetic analysis of human renin demonstrates the histidine proximal to the substrate scissile peptide bond contributes to the unique specificity and pH dependence of this aspartyl protease. Recombinant human renal renin purified from mammalian cell culture appears to be indistinguishable from renin isolated from human kidney with respect to specific activity (1000 Goldblatt units/mg). Recombinant renin contains carbohydrate covalently attached to asparagines at positions 5 and 75 (renin numbering) and disulfide linkages at Cys-51/Cys-58, Cys 217/Cys-221, and Cys-259/Cys-296. Renin pH dependence was evaluated between pH 4.0 and 8.0 by using a synthetic substrate identical with the amino terminus of porcine angiotensinogen (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu*Leu-Val-Tyr-Ser, where the asterisk indicates the scissile peptide bond and the proximal histidine is in italics) and an analogous tetradecapeptide where the proximal histidine was substituted with glutamine. Comparison of the pH profiles shows the catalytic efficiency (V/Km) and maximal velocity (V) of renin are greater above pH 6.5 with the substrate containing histidine proximal to the scissile peptide bond, but below pH 5.0 these parameters are greater with the glutamine substrate analogue. Solvent isotope effects show that proton transfer contributes to the rate limiting step in catalysis with both substrates and that the proximal histidine does not serve as a base in the catalytic mechanism. Molecular modeling indicates the substrate histidine could hydrogen bond to Asp-226 of the enzyme (renin numbering), thus perturbing the ionization of the catalytic aspartyl groups (Asp 38 and Asp-226).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186808 TI - Stabilization of recA protein-ssDNA complexes by the single-stranded DNA binding protein of Escherichia coli. AB - In vitro recombination reactions promoted by the recA protein of Escherichia coli are enhanced by the single-stranded DNA binding protein (SSB). SSB affects the assembly of the filamentous complexes between recA protein and ssDNA that are the active form of the recA protein. Here, we present evidence that SSB plays a complex role in maintaining the stability and activity of recA-ssDNA filaments. Results of ATPase, nuclease protection, and DNA strand exchange assays suggest that the continuous presence of SSB is required to maintain the stability of recA ssDNA complexes under reaction conditions that support their recombination activity. We also report data that indicate that there is a functional distinction between the species of SSB present at 10 mM magnesium chloride, which enhances recA-ssDNA binding, and a species present at 1 mM magnesium chloride, which displaces recA protein from ssDNA. These results are discussed in the context of current models of SSB conformation and of SSB action in recombination activities of the recA protein. PMID- 2186809 TI - The mechanism of protein folding. Implications of in vitro refolding models for de novo protein folding and translocation in the cell. PMID- 2186810 TI - Identification of the tRNA anticodon recognition site of Escherichia coli methionyl-tRNA synthetase. AB - We have previously shown that the anticodon of methionine tRNAs contains most, if not all, of the nucleotides required for specific recognition of tRNA substrates by Escherichia coli methionyl-tRNA synthetase [Schulman, L. H., & Pelka, H. (1988) Science 242, 765-768]. Previous cross-linking experiments have also identified a site in the synthetase that lies within 14 A of the anticodon binding domain [Leon, O., & Schulman, L. H. (1987) Biochemistry 26, 5416-5422]. In the present work, we have carried out site-directed mutagenesis of this domain, creating conservative amino acid changes at residues that contain side chains having potential hydrogen-bond donors or acceptors. Only one of these changes, converting Trp461----Phe, had a significant effect on aminoacylation. The mutant enzyme showed an approximately 60-100-fold increase in Km for methionine tRNAs, with little or no change in the Km for methionine or ATP or in the maximal velocity of the aminoacylation reaction. Conversion of the adjacent Pro460 to Leu resulted in a smaller increase in Km for tRNA(Mets), with no change in the other kinetic parameters. Examination of the interaction of the mutant enzymes with a series of tRNA(Met) derivatives containing base substitutions in the anticodon revealed sequence-specific interactions between the Phe461 mutant and different anticodons. Km values were highest for tRNA(mMet) derivatives containing the normal anticodon wobble base C. Base substitutions at this site decreased the Km for aminoacylation by the Phe461 mutant, while increasing the Km for the wild-type enzyme and for the Leu460 mutant to values greater than 100 microM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186811 TI - Purification and characterization of the D-alanyl-D-alanine-adding enzyme from Escherichia coli. AB - The Escherichia coli D-alanyl-D-alanine-adding enzyme, which catalyzes the final cytoplasmic step in the biosynthesis of the bacterial peptidoglycan precursor UDP N-acetylmuramyl-L-Ala-gamma-D-Glu-meso-diaminopimelyl-D-Ala-D- Ala, has been purified to homogeneity from an E. coli strain that harbors a recombinant plasmid bearing the structural gene for this enzyme, murF. The enzyme is a monomer of molecular weight 49,000, and it has a turnover number of 784 min-1 for ATP-driven amide bond formation. Experiments monitoring the fate of radiolabeled UDP-N acetylmuramyl-L-Ala-gamma-D-Glu-meso-2,6-diaminopimelate and D-trifluoroalanine proved that the preceding enzyme in the D-alanine branch pathway, D-alanine:D alanine ligase (ADP), is capable of synthesizing fluorinated dipeptides, which the D-Ala-D-Ala-adding enzyme can then incorporate to form UDP-N-acetylmuramyl-L Ala-gamma-D-Glu-meso-2,6-diaminopimelyl-D-++ +trifluoroAla-D- trifluoroAla. PMID- 2186812 TI - Allosteric effects acting over a distance of 20-25 A in the Escherichia coli tryptophan synthase bienzyme complex increase ligand affinity and cause redistribution of covalent intermediates. AB - The reactions of L-histidine (L-His) and L-tryptophan (L-Trp) with the alpha 2 beta 2 complex of Escherichia coli tryptophan synthase are introduced as probes both of beta-subunit catalysis and of ligand-mediated alpha-beta allosteric interactions. Binding of DL-alpha-glycerol 3-phosphate (GP), an analogue of 3 indole-D-glycerol 3'-phosphate (IGP), to the alpha-catalytic site increases the affinity of alpha 2 beta 2 for L-His 4.5-fold and the affinity for L-Trp 17-fold and brings about a redistribution of beta-bound intermediates that favors the quinonoids derived from each amino acid. Inorganic phosphate (Pi) (presumably via binding to the alpha-catalytic site) influences the distribution of L-His intermediates as does GP. Previous binding studies [Heyn, M. P., & Weischet, W. O. (1975) Biochemistry 14, 2962-2968] indicate that when the phosphoryl group subsite of the alpha-catalytic site is occupied by GP or Pi, a high-affinity indole subsite is induced at the alpha-catalytic site. Interaction of benzimidazole (BZ), an analogue of indole, with this site also shifts the distribution of beta-bound L-His intermediates in favor of the L-His quinonoid. In the absence of Pi or GP, BZ interacts primarily at the beta-catalytic site and competes with L-His for the beta-subunit indole subsite. Since L-His and GP (or Pi) are substrate analogues and L-Trp is the physiological product, these allosteric effects likely take place with the natural substrates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186813 TI - Reaction of uridine diphosphate galactose 4-epimerase with a suicide inactivator. AB - UDPgalactose 4-epimerase from Escherichia coli is rapidly inactivated by the compounds uridine 5'-diphosphate chloroacetol (UDC) and uridine 5'-diphosphate bromoacetol (UDB). Both UDC and UDB inactivate the enzyme in neutral solution concomitant with the appearance of chromophores absorbing maximally at 325 and 328 nm, respectively. The reaction of UDC with the enzyme follows saturation kinetics characterized by a KD of 0.110 mM and kinact of 0.84 min-1 at pH 8.5 and ionic strength 0.2 M. The inactivation by UDC is competitively inhibited by competitive inhibitors of UDPgalactose 4-epimerase, and it is accompanied by the tight but noncovalent binding of UDC to the enzyme in a stoichiometry of 1 mol of UDC/mol of enzyme dimer, corresponding to 1 mol of UDC/mol of enzyme-bound NAD+. The inactivation of epimerase by uridine 5'-diphosphate [2H2]chloroacetol proceeds with a primary kinetic isotope effect (kH/kD) of 1.4. The inactivation mechanism is proposed to involve a minimum of three steps: (a) reversible binding of UDC to the active site of UDPgalactose 4-epimerase; (b) enolization of the chloroacetol moiety of enzyme-bound UDC, catalyzed by an enzymic general base at the active site; (c) alkylation of the nicotinamide ring of NAD+ at the active site by the chloroacetol enolate. The resulting adduct between UDC and NAD+ is proposed to be the chromophore with lambda max at 325 nm. The enzymic general base required to facilitate proton transfer in redox catalysis by this enzyme may be the general base that facilitates enolization of the chloroacetol moiety of UDC in the inactivation reaction. PMID- 2186814 TI - Norepinephrine-stimulated in vitro release of luteinizing hormone-releasing hormone (LHRH) from median eminence tissue is facilitated by inhibition of LHRH degrading activity in hens. AB - We and others have previously reported the existence of hypothalamic and anterior pituitary (AP) enzymes that degrade luteinizing hormone (LH)-releasing hormone (LHRH). We have further characterized these LHRH-degrading activities (LHRH-DA) and in addition assessed the role of LHRH-DA in LHRH release from median eminence (ME) tissue in vitro. Major LHRH-DA components were separated and their molecular weights were estimated by gel filtration chromatography. The role of LHRH-DA in LHRH release was determined by release studies from isolated ME, in the presence and absence of N-tosyl L-phenylalanine chloromethyl ketone (TPCK) and/or norepinephrine (NEpi). Degradation and in vitro release studies were performed by using LHRH analogs with amino acid substitutions at their 5-6 bond. Biological activity of these analogs was assessed by measuring in vitro LH release from dispersed anterior pituitary cells. LHRH-DA was determined by high-performance liquid chromatography; LH and LHRH were measured by radioimmunoassay. Separation of LHRH-DA by gel filtration chromatography yielded two major enzymatic activities: a Tyr5-Gly6 cleaving endopeptidase and a post-proline cleaving enzyme. Although LHRH-DA from AP and ME produced identical degradation fragments, the former had 3-fold greater specific activity than the latter. LHRH moieties with a Tyr5-Gly6 bond substitution were more resistant to enzymatic degradation and had greater biological activity than LHRH moieties with a Tyr5-Gly6 bond. TPCK decreased LHRH-DA and increased NEpi-stimulated in vitro release of LHRH from isolated ME.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186815 TI - Characterization of rat testicular peritubular myoid cells in culture: alpha smooth muscle isoactin is a specific differentiation marker. AB - In frozen sections of testes from 20-day-old rats, alpha-smooth muscle (SM) isoactin was prominently immunostained in the peritubular tissue and in vascular walls, but not in areas populated by germinal cells, interstitial cells, or Sertoli cells. Peritubular myoid cell (PMC)-enriched preparations were isolated by two different procedures involving our previously published sequential enzymatic treatment ("conventional peritubular cell [PC]-enriched preparation") and by density-gradient purification of PMC from these preparations. The properties of different populations of PMC in culture were compared with respect to plating efficiency, rates of proliferation, and presence of cytoskeletal proteins. PMC, maintained in culture under defined conditions, contained proteins immunoreactive with monoclonal antibodies against alpha-SM isoactin. This was detected by immunostaining and by Western blots of cell extracts subjected to gel electrophoresis. Neither Sertoli cells, skin fibroblasts, bovine endothelial cells, nor glial cells contained alpha-SM isoactin detectable by the above techniques. We report the ontogeny of alpha-SM isoactin in the peritubular tissue of testes at different stages of gonadal development, and show that it is detectable within 8 days after birth. In addition, we describe immunocytochemical changes that occur during culture in various media of PMC prepared from testes of 20-day-old rats. We compare the use of alpha-SM isoactin as a differentiation marker for PMC with the use of desmin in facilitating the identification of PMC, and in following alterations in phenotype during culture in various culture media. Data presented demonstrate that about 81% of cells in the "conventional PC enriched preparation," and about 94% of cells in the more purified populations of PMC were positive for alpha-SM isoactin in cells maintained in culture for 18 h after plating. These same PMC also were shown to express vimentin and plasminogen activator inhibitor, type 1. We conclude that alpha-SM isoactin is an excellent specific marker for PMC in seminiferous tubules and in culture. PMID- 2186816 TI - [Group A streptococcal polysaccharide--stimulator of nonspecific cytotoxic reaction in autologous system of spleen cells]. AB - p4 was shown the ability of group A streptococcal polysaccharide (A-PS) to stimulate nonspecific cytotoxic effect of spleen cells on autologous adherent cells (macrophages). The stimulating effect can be observed in vivo under the treatment of spleen cells with A-PS and any antigen (BSA, PPD, M-protein of group A streptococci). In the presence of antigen A-PS can induce nonspecific cytotoxic effect of normal spleen cells (mice CBA, BaLB/c) and of the mice with DHT and therefore these two immunologic phenomena do not depend on each other. Because A PS has cross-reactive (CR) determinant with thymus epithelial antigen (factor), it can be assumed that via the CR determinant A-PS links with T-cells receptor for this thymus factor and thus realized the stimulating effect as it's functional analogue. PMID- 2186817 TI - [Significance of raised production of eicosanoids during the increase of immunosuppressive activity of the serum after hemosorption]. PMID- 2186818 TI - Manipulations of cellular iron metabolism for modulating normal and malignant cell proliferation: achievements and prospects. PMID- 2186819 TI - Identification of two risk groups in childhood acute myelogenous leukemia after therapy intensification in study AML-BFM-83 as compared with study AML-BFM-78. AML-BFM Study Group. AB - The main difference between the two cooperative studies on therapy of childhood acute myelogenous leukemia AML-BFM-78 and AML-BFM-83 was the addition of an 8-day ADE (cytosine arabinoside, daunorubicin, etoposide) induction treatment in the second study. Due to this intensification, the relapse rate, but not the rate of induction failures, was reduced. The probability of a 6-year event-free survival increased from 38%, SD 4%, in study AML-BFM-78 to 49%, SD 4%, in study AML-BFM 83, P = .08. The improvement of the 6-year event-free interval (EFI) was significant in the second study (61%, SD 4%, versus 47%, SD 5%, P less than .05); it was restricted to the FAB types M1 through M4 (EFI: 67%, SD 5%, versus 45%, SD 5%, P less than .01). The difference in EFI seen in FAB M5 was not statistically significant (EFI: 40%, SD 10%, versus 63%, SD 11%, NS). According to the results of the second study, two different risk groups (low and high) could be identified by combinations of predominantly pretherapeutic parameters. The low risk group, comprising 37% of the patients who achieved complete remission, included the FAB types with granulocytic differentiation and specific additional features: FAB M1 with Auer rods, FAB M2 with white blood cell count of less than 20,000/microL, FAB M3 all patients, and FAB M4 with eosinophilia. The 6-year Kaplan-Meier estimation of EFI is 91%, SD 4%, compared with 42%, SD 6% in the high risk group. In future studies based on the AML-BFM-83 treatment, bone marrow transplantation in first remission should be mandatory only for children of the high risk group. PMID- 2186820 TI - Effects of parenteral recombinant human macrophage colony-stimulating factor on monocyte number, phenotype, and antitumor cytotoxicity in nonhuman primates. AB - Recombinant human macrophage colony-stimulating factor (rhM-CSF) was given to cynomolgus monkeys by continuous intravenous infusion or subcutaneous injection, at a dose of 50 to 100 micrograms/kg/d in repetitive 14-day cycles. Starting within 24 to 48 hours of initiation of rhM-CSF, there was a progressive increase in the number of circulating monocytes, from a baseline of 811 +/- 253 cells/microL to a peak of 3,495 +/- 712 cells/microL on day 5 to 7. Many of these cells were large, granular, and extensively vacuolated. The expanded cell population expressed HLA-DR, LFA3, CD11b (904), and CD14 (MY4), and was 77% CD16 (FcRIII) positive by two-color cytofluorometry. In functional assays, fresh monocytes showed little cytotoxicity against cultured human melanoma cells (SKMel 1), with or without prior rhM-CSF treatment. However, after 3 days of in vitro culture in rhM-CSF, monocytes from treated animals mediated efficient antibody dependent cytotoxicity (ADCC) against SKMel-1 using the murine monoclonal antibody 3F8 (IgG3, anti-ganglioside GD2). Under the same conditions, monocytes from control animals showed little ADCC (17% versus 82%, P less than .05). Antitumor cytotoxicity in the absence of antibody was less efficient and was not significantly different between the two groups. There was a mild decrease in platelet count during rhM-CSF treatment, without clinical symptoms. No abnormalities of serum biochemical parameters were seen. We conclude that parenteral rhM-CSF increases the number of circulating monocytes in nonhuman primates, and that these monocytes mediate increased antitumor ADCC after a brief period of in vitro differentiation. This study has implications for the design of possible future clinical trials combining antitumor monoclonal antibodies and rhM CSF. PMID- 2186821 TI - Transferrin-reticulocyte cycle time in rat reticulocytes. AB - The uptake and release of 131I-labelled diferric transferrin by rat reticulocytes was examined both in vitro and in vivo. Cycle time in vitro was estimated to be 2.5 min in iron-deficient reticulocytes and 2.3 min in phenylhydrazine-produced reticulocytes. In vivo reticulocyte uptake and release of labelled diferric transferrin injected in the iron-deficient rat averaged 1.7 min. PMID- 2186822 TI - Echo Doppler analysis of lymphomatous lymph nodes. PMID- 2186823 TI - Lead poisoning: an age old problem. PMID- 2186824 TI - Mann overboard. PMID- 2186825 TI - Early diet of preterm infants and development of allergic or atopic disease: randomised prospective study. AB - OBJECTIVE: To study the effect of early diet on the development of allergic reactions in infants born preterm. DESIGN: Two randomised prospective trails. In trail A infants were randomly allocated banked donor milk or preterm formula as their sole diet or (separately randomised) as a supplement to their mother's expressed breast milk. In trial B infants were allocated term or preterm formula. A blind follow up examination was done 18 months after the expected date of birth. SETTING: Neonatal units of hospitals in Cambridge, Ipswich, King's Lynn, Norwich, and Sheffield. Outpatient follow up. PARTICIPANTS: 777 Infants with a birth weight less than 1850 g born during 1982 to 1984. MAIN OUTCOME MEASURES: Development of eczema, allergic reactions to food or drugs, and asthma or wheezing by nine and 18 months after term. Whenever possible the observations were confirmed by rechallenge or clinical examination. RESULTS: At 18 months after term there was no difference in the incidence of allergic reactions between dietary groups in either trial. In the subgroup of infants with a family history of atopy, however, those in trial A who received preterm formula rather than human milk had a significantly greater risk of developing one or more allergic reactions (notably eczema) by 18 months (odds ratio 3.6; 95% confidence interval 1.4 to 9.1). CONCLUSIONS: Feeding neonates on formulas based on cows' milk, including those with a high protein content, did not increase the overall risk of allergy. Nevertheless, in the subgroup with a family history of atopy early exposure to cows' milk increased the risk of a wide range of allergic reactions, especially eczema. PMID- 2186826 TI - Mortality in elderly patients admitted for respite care. AB - OBJECTIVE: To determine whether admitting elderly patients to hospital to give temporary relief to their carers is associated with increased mortality. DESIGN: Prospective multicentre study comparing the mortality of patients admitted on a one off or rotational basis with that experienced while they were awaiting admission. SETTING: A wide range of urban and rural district general, geriatric or long stay, and general practitioner hospitals. PATIENTS: 474 Patients aged 70 or over who had 601 admissions. MAIN OUTCOME MEASURE: Death. RESULTS: 16 (3.4%) Of the 474 patients (2.7% of all 601 admissions) died while in hospital during an average stay of 15.7 days whereas 23 (4.9%) patients died while awaiting admission (average waiting time was 34.2 days). The 16 deaths in hospital and the 23 deaths during the longer waiting period correspond to death rates of 19.9 and 12.5 per 10,000 person days respectively. The difference between these of 7.4 is not statistically significant (95% confidence interval -3.6 to 18.3). The estimated relative risk of dying in hospital is 1.59 but the 95% confidence interval is wide (0.84 to 3.01). CONCLUSION: Although the death rates are slightly higher in those admitted to hospital for relief care than in those awaiting admission, the difference was not significant, and the death rate in both groups was reassuringly small. PMID- 2186827 TI - ABC of transfusion. Fetal and neonatal transfusion. PMID- 2186828 TI - Thrombolysis and the general practitioner. 1. Practicable only under certain circumstances. PMID- 2186829 TI - Thrombolysis and the general practitioner. 2. Useful after careful evaluation of patients. PMID- 2186830 TI - Massive haemoptysis. PMID- 2186831 TI - Idiopathic dilated cardiomyopathy. PMID- 2186832 TI - Long term propranolol treatment and changes in body weight after myocardial infarction. AB - OBJECTIVE: To determine the effect of long term propranolol treatment on body weight. DESIGN: Retrospective analysis of data from a placebo controlled randomised double blind clinical trial (the beta blocker heart attack trial). PATIENTS: 3837 Men and women randomised 5-21 days after an acute myocardial infarction to treatment with placebo or propranolol for up to 40 months. Patients were followed up at annual visits. MAIN OUTCOME MEASURE: Changes in body weight. RESULTS: At the first annual visit patients treated with propranolol had gained more weight than those given placebo (mean weight gain 2.3 kg v 1.2 kg respectively, mean difference 1.2 kg (95% confidence interval 0.9 to 1.5]. These group differences remained at the second and third annual visits. The difference in weight gain could not be explained by discrepancies in the use of diuretics or in physical activity and was similar in patients of both sexes and of all ages. CONCLUSION: Long term beta blockade results in a sustained weight gain. PMID- 2186833 TI - Theophylline in the management of airflow obstruction. 1. Much evidence suggests that theophylline is valuable. PMID- 2186835 TI - Reconstruction of the haemopoietic and immune systems after marrow transplantation. PMID- 2186834 TI - Theophylline in the management of airflow obstruction. 2. Difficult drugs to use, few clinical indications. AB - The narrow therapeutic index, potential toxicity, and need to monitor plasma concentrations make theophyllines difficult to use. Other drugs provide comparable or better bronchodilator and prophylactic efficacy. In asthma theophyllines should be considered for chronic stable asthma when treatment with optimal doses of inhaled steroids and bronchodilators fails to provide adequate control; for nocturnal asthma; and for prophylaxis and relief of symptoms in children and adults when inhaled treatment cannot be given. In general, theophyllines cannot be recommended for chronic airflow obstruction. A trial of theophylline is reasonable in individual patients whose symptoms remain troublesome despite a trial of steroids and optimal doses of inhaled bronchodilators. PMID- 2186836 TI - Mixed chimerism after allogeneic marrow transplantation for leukaemia: correlation with dose of total body irradiation and graft-versus-host disease. AB - Fifty-four patients allografted for leukaemia were evaluated at various intervals after bone marrow transplantation for the presence of host haemopoiesis using red blood cell and cytogenetic markers. Out of 40 patients in remission, 10 showed functional host and donor haemopoiesis (mixed chimerism), whereas in the other 30 (complete chimerism) host haemopoiesis was never detected. Seven of the 14 evaluable patients who relapsed showed the reappearance of host haemopoiesis at the time of relapse. Analysis of the dose of total body irradiation (TBI) indicated that patients who achieved mixed chimerism, whether or not they relapsed, had received significantly lower doses than those with complete chimerism. However, some patients with complete chimerism had received a TBI dose equivalent to the dose received by those with mixed chimerism, suggesting that the TBI dose is not the only factor determining the reappearance of host haemopoiesis. The data on chimerism and relapse suggest that there is heterogeneity in radiosensitivity between normal marrow cells and leukaemic cells, and also within the different types of leukaemia. The incidence/severity of acute and chronic graft-versus-host-disease (GVHD) was significantly higher in patients with complete chimerism than in mixed chimeras, suggesting that mixed chimerism may play a role in the development of tolerance. Alternatively the absence of GVHD (i.e. tolerance) may be responsible for the persistence of host haemopoietic cells. PMID- 2186837 TI - A Nordic registry for volunteer marrow donors? AB - A meeting took place in Helsinki in November 1989 to consider the scientific, clinical and financial implications of establishing a registry of volunteer bone marrow transplant donors in the Nordic countries. The possible contributions of new techniques for defining HLA genes and gene products, notably the study of restriction fragment length polymorphisms and allele specific oligonucleotides, and for selecting optimal donors, notably the assay of cytotoxic T lymphocyte precursors in the graft-versus-host direction, were discussed. The differing approaches actually used to establish new donor registries in the United Kingdom, United States and France were contrasted. The clinical results of using unrelated donors for transplanting patients with chronic myeloid leukaemia, severe aplastic anaemia and other haematological diseases were presented. Finally, participants heard details of the International Marrow Unrelated Search and Transplant Study which collects and analyses data internationally on patients for whom searches are initiated and on patients who actually receive transplants from volunteer donors. PMID- 2186838 TI - Fertility after torsion of the spermatic cord. PMID- 2186839 TI - Ultrasound cystography in the diagnosis of vesicoureteric reflux. AB - Vesicoureteric reflux is common in children with urinary tract infection and may cause end-stage renal failure. The diagnosis is usually based on micturating cystourethrography (MCU). We describe an alternative technique using ultrasound during bladder infusion with agitated saline. Comparison of the 2 methods shows ultrasound to be 100% sensitive in the detection of grades 3 and 4 reflux. Conclusive evidence of reflux was seen in 2 cases where MCU was subsequently normal, questioning the role of MCU as the gold standard. PMID- 2186840 TI - Malignant lymphoma of the lower urinary tract. A clinicopathological study with review of the literature. AB - The clinical and histopathological findings are reported in 3 primary malignant lymphomas of the lower urinary tract. Two arose in the bladders of a 70-year-old man and a 67-year-old woman. The first was histologically low grade and the patient remains free of disease after more than 7 years. The second was an intermediate grade neoplasm and the patient died after 39 months. The third tumour was found in the urethra of a 76-year-old woman and it appears to represent only the third primary malignant lymphoma described at this site. The bladder is an uncommon primary site of extranodal lymphoma. Most patients present with haematuria and cystoscopy shows 1 or more solid, round, tumour-like masses. Histological grade, particularly follicle formation, appears to have predictive value. PMID- 2186841 TI - Megestrol acetate in relapsed carcinoma of prostate. AB - A series of 22 patients with advanced carcinoma of the prostate who had failed first-line hormonal therapy (orchiectomy, stilboestrol, luteinising hormone releasing hormone agonist) were treated with 160 mg megestrol acetate daily. Treatment was well tolerated, side effects were minimal and 21 patients were evaluable. There were no complete or partial responses, although 8 patients had a good subjective response. In 6 patients the disease was stabilised for 6 to 12 months and there was a 40 to 50% reduction in their prostatic acid phosphatase (PAP) levels. It was concluded that megestrol acetate has a role as second-line hormonal therapy in the management of prostatic carcinoma. PMID- 2186842 TI - Urethral calculi. AB - We present 56 patients with urethral calculi. In males the commonest location was the posterior urethra; 46 patients complained of dysuria but urinary retention was present in only 7. In 9 patients with penile urethral calculi, 6 had associated urethral disease (urethral stricture in 5 and urethral diverticula in 1). Transurethral litholapaxy or lithotripsy after retrograde manipulation was performed in 33 patients. Endoscopic manipulation was found to be the safest procedure. PMID- 2186843 TI - Urachal cyst: an unusual cause of hydronephrosis. PMID- 2186844 TI - Ethanol inhibits NMDA-activated current but does not alter GABA-activated current in an isolated adult mammalian neuron. AB - The effects of ethanol (EtOH) on membrane ion currents activated by N-methyl-D aspartate (NMDA) and gamma-aminobutyric acid (GABA) were studied under voltage clamp conditions in isolated sensory neurons within hours of being dissociated from adult rats. The amplitude of the ion current activated by NMDA was decreased in the presence of 2.5-100 mM EtOH (IC50, 10 mM or 0.05% EtOH), a concentration range that produces intoxication. The amplitude of the GABA-activated Cl- current, on the other hand, was not significantly affected by this concentration range of EtOH. The observations suggest that some of the neural and cognitive impairments associated with EtOH intoxication may result from inhibition of the NMDA-activated ion current. PMID- 2186845 TI - Cerebral amyloid in mice with Creutzfeldt-Jakob disease is influenced by the strain of the infectious agent. AB - We examined Fukuoka-1 and Fukuoka-2 mouse-adapted Creutzfeldt-Jakob disease strains. Mice infected with the Fukuoka-2 strain have a higher incidence of kuru plaques, a higher concentration of proteinase-resistant prion protein, and a higher infectivity titer than do mice with the Fukuoka-1 strain. Thus, it must be kept in mind that there is a difference in the strain of the infectious agent in murine Creutzfeldt-Jakob disease. PMID- 2186846 TI - Alterations in gonadotropin-releasing hormone immunoactivities in discrete brain areas of male goldfish during spawning behavior. AB - In male goldfish, spawning behavior and gonadotropin (GtH) secretion are stimulated during exposure to females which were induced to perform spawning behavior by treatment with prostaglandin F2 alpha (PG). In this study, exposure to PG-treated females for 1 or 2 h significantly increased serum GtH levels, and GtH-releasing hormone (GnRH) concentrations in the olfactory bulbs, telencephalon and hypothalamus, indicating that spawning behavior can influence cellular events of the brain GnRH neuronal system and pituitary GtH secretion in male goldfish. To study the role of the olfactory system in the hormonal responses to PG-treated females, bilateral sectioning of olfactory tracts (OTX), medial (mOTX) or lateral (lOTX) olfactory tract were carried out in male goldfish. Both OTX and mOTX, but not lOTX, blocked the behavioral response of male goldfish to PG-treated females and abolished the increases in serum GtH and brain GnRH levels, suggesting that alterations in pituitary GtH secretion and brain GnRH levels are associated with a pheromonal activation of spawning behavior through the medial olfactory tracts in male goldfish. This behavioral activation of the GnRH neuronal system provides a useful physiological model for studying the regulation of GnRH system in male goldfish. PMID- 2186847 TI - Medioventral medulla-induced locomotion. AB - Previous anatomical studies demonstrated the presence of descending projections from the physiologically identified mesencephalic locomotor region (MLR) to the medioventral medulla (MED) in the cat. The present experiments were designed to determine if a similar low threshold locomotion-inducing area is present in the rat medulla. In addition, the nature of the neurochemical control of this area of the brain was explored using localized injections of neurochemical agents in the decerebrate rat during locomotion on a treadmill. A region virtually identical to that reported in the cat was found to lead to controlled locomotion on a treadmill following stimulation at low amplitude currents (less than or equal to 60 microA). Injections of cholinergic agonists into the MED of the rat induced locomotion which could be blocked by injections of cholinergic antagonists. In addition, injections of GABA antagonists were found to induce stepping which could be blocked by injections of GABA or GABA agonists. Substance P (SP) also was found to induce walking following injection into the MED of the rat. Injections of an excitatory amino acid agonist (NMDA) also were found to induce locomotion in the rat. These effects were blocked by injections of an excitatory amino acid antagonist (APV). Since these results had not been reported for the cat MED, a short series of experiments revealed that the MED in the cat also responded to NMDA. PMID- 2186848 TI - Purification of 7 alpha-hydroxysteroid dehydrogenase from Escherichia coli strain 080. AB - Purification studies of 7 alpha-hydroxysteroid dehydrogenase (7 alpha-HSDH) (EC 1.1.1.159) from Escherichia coli 080 showed that 1.59-fold purification could be achieved by heating (60 degrees C for 10 min) the ultracentrifuged enzyme preparation, and 6.46-fold purification was achieved by subsequent precipitation with ammonium sulfate. Further purification on Sephadex G-100 gel gave 10.1-fold purification. After pooling and concentrating the active fractions obtained from the Sephadex G-100 filtration, an 11.1-fold purification was achieved using DEAE cellulose chromatography. The purified enzyme produced a single band on polyacrylamide gel electrophoresis and its molecular weight was determined to be 54,000. The enzyme was immunogenic and showed immunoprecipitation with homologus antisera. PMID- 2186849 TI - The role of anion-exchange resins in the treatment of antibiotic-associated pseudomembranous colitis. PMID- 2186851 TI - CMAJ's first issue. PMID- 2186850 TI - AIDS trials, civil liberties and the social control of therapy: should we embrace new drugs with open arms? PMID- 2186852 TI - The role of surgery in the multimodal treatment of primary gastric non-Hodgkin's lymphomas. A report of 76 cases and review of the literature. AB - Seventy-six patients with primary gastric non-Hodgkin's lymphomas (PGL) were diagnosed, and 75 were treated between 1975 and 1985. According to the Working Formulation 22 patients had low-grade malignant histologic subtypes, 27 intermediate-grade, and 27 high-grade. Twenty-four cases were diagnosed by endoscopic biopsies, 52 through laparotomy biopsies. Forty-five underwent subtotal or total gastric resection; seven were considered unresectable at laparotomy; 23 did not undergo surgery because of the high operative risk, mainly due to advanced age and coexisting diseases; and one died of myocardial infarction a few days after admission, before starting therapy. All patients who did not undergo laparotomy were staged with bipedal lymphangiography or abdominal ultrasonography and/or computed tomography. Stage, evaluated according to the criteria of Musshoff, was I or II1 in 16 cases, II2 in five, and IV in the remaining 55. Treatment modalities included surgery (S), chemotherapy (CT), radiotherapy (RT), and combinations thereof in the following proportions: only S in ten cases, S + CT in 32 cases, S + RT in one case, S + CT + RT in two cases, CT only in 25 cases, CT + RT in five cases. No substantial differences in response to therapy and in survival were found in relation to the different treatments. Ten-year survival was 43% in Stage I or II and 20% in Stage IV. Of the 45 resected patients, five postoperative deaths were recorded (11%). No bleeding or perforations were observed in the 30 unresected patients, and survival of such cases compared with that of the resected ones. These findings, together with data from the literature, suggest that some of the advantages claimed for surgery in PGL (debulking and abatement of the risk of perforation or hemorrhage during CT or RT) have been overestimated in relation to the intrinsic surgical risk and to the possibility of anticancer therapy. Gastric resection may still be unavoidable as a diagnostic procedure in a minority of cases and may represent the primary therapeutic procedure in clinically assessed early-stage and low-risk patients, but it cannot be considered mandatory whenever possible merely for debulking purposes or to obviate possible perforation or hemorrhage. The CT and/or RT can be effective in unresected and even bulky cases, providing minimal risk of severe hemorrhage or perforation. PMID- 2186855 TI - Reversibility of atherosclerosis. PMID- 2186853 TI - Suppression of well-established tumour xenografts by a hybrid-hybrid monoclonal antibody and vinblastine. AB - The hybrid-hybrid monoclonal antibody 28-19-8 has specificity for the tumour associated antigen carcinoembryonic antigen and the vinca alkaloids. This bifunctional antibody has been used to target unmodified vinblastine sulphate to well-established MAWI human tumour xenografts implanted in nude mice. The highly significant suppression of tumour growth achieved throughout treatment has also been sustained for over 2 months after the withdrawal of treatment. Histological examination of excised tumours from treated animals has shown profound changes in their morphology when compared with tumours from control animals. Cells in tumours that had started to grow again after withdrawal of therapy were shown still to express carcinoembryonic antigen, the target antigen recognised by the bispecific antibody. PMID- 2186854 TI - A controlled trial of bestatin in hydatidiform mole. AB - A prospective randomized controlled trial was conducted to study whether Bestatin, an immunomodifier, can reduce the incidence of persistent gestational trophoblastic disease in patients with hydatidiform mole. A group of 21 patients (Bestatin group) received 30 mg Bestatin daily after evacuation of the hydatidiform mole. A second group of 23 patients (control group) did not receive any drug. Blood was taken for white cell counts, differential counts, lymphocyte subset counts (CD2+, CD4+, CD8+ and B cells) and natural killer cell activity before evacuation of the hydatidiform moles. The tests were repeated every 4 weeks after evacuation until the serum beta subunit of human chorionic gonadotropin (beta hCG) had returned to normal or until the patient had to receive chemotherapy because of persistent gestational trophoblastic disease. There was no significant difference in the age of the patients, the pre evacuation serum beta hCG, or the gestational age between the two groups. Chemotherapy was needed by 6 patients in the Bestatin group (28.6%) and 3 patients in the control group (13%) because of persistent gestational trophoblastic disease. There was no significant difference in any of the immunological parameters between the two groups before or after evacuation. We conclude that Bestatin at this dosage does not improve the immunological functions or clinical outcome in patients with hydatidiform mole. PMID- 2186856 TI - Modification of thrombogenic factors in cardiac disease. AB - Thrombosis plays an important role in the development and course of most disorders affecting the heart. No effective methods are available to eliminate the thrombogenic stimulus for those conditions requiring the use of antithrombotic agents for prophylaxis or to arrest a thrombotic event. Available platelet and coagulation inhibitors are effective when properly selected and administered. PMID- 2186857 TI - Psychosocial factors in coronary heart disease. PMID- 2186858 TI - Nutritional treatment of hyperlipidemia and obesity. PMID- 2186859 TI - Treatment of lipoprotein disorders. PMID- 2186860 TI - The role of exercise in the primary and secondary prevention of coronary atherosclerotic heart disease. PMID- 2186861 TI - Supervised and unsupervised exercise for the general population and patients with known cardiac disease. PMID- 2186862 TI - Effects of smoking on the cardiovascular system. PMID- 2186863 TI - Prevention of adult heart disease beginning in the pediatric age. AB - Many advances have now been made in understanding the early natural history of coronary artery disease and essential hypertension, an understanding that these diseases begin in childhood and that CVD relates to clinical cardiovascular risk factors. Methods have now been established to determine risk factors in the pediatric age and, with a family history, to begin to identify children at potential risk for premature heart disease. Advances have also been made in developing models for intervention and beginning prevention through both high risk and population strategies directed at schoolchildren. Obviously, both approaches are needed and complement each other. An impressive future is ahead for effective preventive cardiology beginning with children by incorporation of cardiovascular health education and health promotion in elementary schools. Applying behavioral concepts to intervention programs can strengthen their chances of success. The overall good of having children adopt healthy life-styles with an understanding of their necessity is now attainable. It will be the responsibility of physicians to guide the direction of programs being promoted for children. PMID- 2186864 TI - Modification of the smoking habit. PMID- 2186865 TI - Cardiovascular risk factors. AB - Atherosclerosis and its various clinical manifestations are now highly predictable and preventable diseases. Dyslipidemia appears to be a necessary cause, and hypertension and cigarette smoking are both powerful and modifiable contributing causes. Health professionals should incorporate cardiovascular risk assessment and risk factor modification within the context of their delivery of personal health services. Such services probably already have contributed to the decline of cardiovascular mortality, and the current levels of risk factors in the United States population indicate that substantial further reduction should be possibly by creating a smoke-free environment by the year 2000 and by implementing the recommendations of the National Cholesterol and High Blood Pressure Education Programs. PMID- 2186866 TI - Hypertension as a risk factor. AB - Hypertension has been demonstrated to be a clear risk factor for CHD. The finding that hypertension is a risk factor has been demonstrated in observation studies, actuarial data and clinical trials. The relationship between blood pressure and CHD is strong. As blood pressure rises, risk for cardiovascular events increases. This is true for both sexes, for blacks and whites, and for all age categories. Clinical trials, both large and small, have demonstrated that lowering blood pressure can reverse the risk and reduce morbidity and mortality. This cause-and effect relationship has been replicated consistently, and there is not one well controlled trial of adequate size that has failed to show this finding. It is important to know which concept of risk to use in developing hypertensive programs. The concept of relative risk is useful to determine whether a public health program is needed within a population, but it has less value in identifying which subset of the population in which to intervene. In essence, relative risk is used to mandate a program but cannot determine where the program should be directed. Hypertension attributable risk describes which individuals are at greatest risk and serves to guide planners as to which groups have the greatest mortality once blood pressure becomes elevated. Population attributable risk becomes the most useful tool in identifying or locating those communities of highest-risk individuals. PMID- 2186867 TI - Systolic hypertension in the elderly: controlled or uncontrolled. AB - ISH is a distinct pathogenetic entity defined by SBP readings of greater than or equal to 160 and DBP less than 90 mmHg. The etiology, although not well understood, is in some manner related to a reduction in connective tissue elasticity of large blood vessels and an increase in aortic impedance or a decrease in aortic wall compliance. The pathophysiologic consequences include an increased resistance to systolic ejection of blood and a disproportionate increase in SBP. Although not directly related, there is an important increase in peripheral vascular resistance. The prevalence of ISH in several studies is about 7 percent in those over age 60 and increases with age to nearly 20 percent in those over age 80. There is higher prevalence in females and nonwhites. The guidelines for detection of ISH are similar to those for blood pressure evaluation in general. Precautions for detection and evaluation in the elderly include multiple blood pressure measurements in the fasting state and sitting and supine blood pressure measurements before and during therapy. Pseudohypertension, although rare, should be kept in mind. There is a clear risk associated with ISH for stroke, CVD, and premature death, which increases with age and rising levels of SBP. ISH can be controlled effectively with pharmacologic therapies. A reasonable goal is a 20 mmHg reduction in systolic pressure. Proof of reduced risk for stroke, CHD, and death in those with controlled ISH remains to be demonstrated. The SHEP pilot study has demonstrated feasibility of addressing this issue. The full-scale SHEP study addresses this issue and has completed recruitment of the desired sample size and is in follow-up phase. Scheduled completion is in 1991. While we wait for the SHEP full-scale trial results, the prudent approach is for nonpharmacologic therapy and use of pharmacologic agents in that group of patients who demonstrate a large cardiovascular risk burden or increasing symptoms specifically associated with hypertension. The decision to treat must be on an individual patient basis. Pharmacologic therapy is possible in most patients with few or no adverse effects. The "low and slow" approach to therapy is helpful in minimizing these adverse effects. Low-dose diuretics have been documented to be effective in blood pressure control. Chlorthalidone, 12.5 or 25 mg per day, is suggested. Other agents, such as beta-blockers, reserpine, ACE inhibitors, and calcium channel blockers, are best used as Step 2 agents. PMID- 2186868 TI - Prevention of sudden cardiac death. PMID- 2186869 TI - Immunocytochemical localization and immunochemical characterization of an insulin related peptide in the insect Leucophaea maderae. AB - Immunocytochemical tests with eight monoclonal antibodies against either bovine or human insulin and seven polyclonal antibodies against bovine insulin were carried out to determine the presence of insulin-like neuropeptides in the brain and affiliated neuroendocrine structures of the insect Leucophaea maderae. Reaction products identified in the brain, subesophageal ganglion, and corpus cardiacum-corpus allatum complex indicate the presence of materials resembling mammalian insulins in its antigenic properties. The immunostaining observed with monoclonal antibodies appears to indicate the occurrence of an insulin-related peptide that shows sequential similarities with parts of both the A- and B-chains of mammalian insulin molecules. These suppositions are supported by the results of dot-blot and two-site time-resolved immunofluorometric assay (TRI-IFMA) screenings of fractions of Leucophaea tissue extracts obtained by chromatography. The polyclonal antibodies yielded reaction products in some of the same areas and in additional parts of the neuroendocrine system not visualized by the monoclonal antibodies. Immunoreaction was observed in the following areas: the pars intercerebralis of the protocerebrum, the nervi corporis cardiaci I transporting insulin-like material to the corpus cardiacum, the dorsolateral protocerebral area and the optic lobes, the deutocerebrum, the tritocerebrum, and the subesophageal ganglion. In addition, smaller cell bodies with immunoreactive deposits occur at the border between proto- and deuto-cerebrum, and in the central area of the protocerebrum. The distribution of reactive material in the corpus cardiacum-corpus allatum complex after use of both groups of antibodies was the same.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186870 TI - Present status of genetic engineering and biotechnology in South Korea. PMID- 2186871 TI - Aerosols for delivery of therapeutic and diagnostic agents to the respiratory tract. AB - Inhaled therapeutic and diagnostic aerosols are examples of targeted delivery systems: they achieve high concentration in the respiratory tract (the usual target organ with these systems) while appearing in low concentrations in other parts of the human body. Development and use of inhalation aerosols requires an appreciation of the properties of these dynamic systems and the ways in which they interact with the anatomically and pathophysiologically complex human respiratory tract. The amounts of aerosol particles, or droplets, initially deposited at various sites in the respiratory tract will determine the intensity of local effects as well as the rate of clearance of these materials from the respiratory lumen. This activity can be modulated by suitable formulation intervention, such as presentation of the active agent in a slow releasing form carrier. Extension of duration of action of inhaled drugs by such means could be possible. As more discriminating methods for location of receptors and for the following of the fate of inhaled drugs and their carriers are becoming available, the ultimate potential for improvement of selective toxicity of agents used in pulmonary therapy by direct delivery into the respiratory tract can be critically evaluated. PMID- 2186872 TI - Immunotherapy with monomethoxypolyethylene glycol modified allergens. AB - On the basis of the results of experiments in naive mice, i.e., in mice which had not been presensitized, it was anticipated that mPEG-modified allergens would suppress the specific IgE response in allergic humans. However, only minor or no suppression of IgE antibodies was induced on administration of mPEG conjugates in allergic patients with a longstanding IgE response. This observation was later confirmed in pre-sensitized animals. The mPEG-modified allergens can be synthesized in a reproducible manner. This makes mPEG-modified allergens suitable for production and quality control. There is indirect evidence, i.e., identification of IgE and IgG antibody stimulation against all identified allergens, that the relevant determinants are available for processing by the immune system. By contrast, the polymerization of allergens by formaldehyde or glutaraldehyde leads to ill-defined, cross-linked high molecular weight materials. As in the case of other modified allergens, mPEG-modified allergens have been developed primarily because of their lower allergenicity than the original allergen preparations. However, they also retain clinical efficacy of the same magnitude as that induced by unmodified allergen preparations, which is a prerequisite for clinical use. IT with mPEG-modified pollen allergen preparations has been proven to be as effective as IT with unmodified allergens, when these preparations are given in similar doses. Furthermore, a more pronounced beneficial effect can be obtained with higher doses of mPEG-modified allergen, without the risk of side effects which are often precipitated by unmodified allergens. Therefore, it seems reasonable to suggest that children and young adults with developing sensitivity to perennial allergens, and without chronic changes of the bronchial mucosa, are the most suitable candidates for IT with mPEG-modified allergen preparations. Mite asthma, which always includes bronchial inflammation and nonspecific hyperresponsiveness, represents a more complicated model. In mite asthmatics mPEG-modified mite allergen preparations were safer than the corresponding unmodified preparation. Although bronchial sensitivity to allergen and histamine did not change significantly in mite asthmatics during the observation time, it appears that IT with mPEG-modified mite allergen led to a decrease in the releasability of histamine from skin mast cells, as measured by SPT, to a similar degree as observed in pollinosis patients. Therefore, it may be inferred that the allergic component of asthma might be influenced by IT with mPEG allergens. As a consequence, before the start of IT, the degree of reversibility of pathophysiological changes in the bronchial wall should be considered.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2186873 TI - An enzymatic method for the kinetic measurement of L-asparaginase activity and L asparagine with an ammonia gas-sensing electrode. AB - A simple kinetic method to assay L-asparaginase and L-asparagine with an ammonia gas-sensing electrode is described. The method is based upon the de-amination of L-asparagine by L-asparaginase from Escherichia coli, resulting in the production of ammonia. The initial rate (mV/min) of ammonia release is proportional to the activity of L-asparaginase and also to the concentration of L-asparagine in the presence of a large amount of the enzyme. Optimal temperature, buffer composition and pH for the assays are specified. L-Asparaginase was determined in the range of 0.4-1.6 U in a 0.1 ml sample; the recovery was 98.1-103.8% for 16 determinations and sigma n was 1.59. L-Asparagine was determined in the concentration range of 1 x 10(-4)--1 x 10(-3) M with sigma n-1 1.92. The method was applied to the determination of 1-5 x 10(-4) M asparagine added to human serum with sigma n-1 1.96 for 5 determinations. PMID- 2186874 TI - Kinetics of befunolol reductase from rabbit liver. AB - The kinetic mechanism for the reduction of befunolol catalyzed by befunolol reductase from rabbit liver was investigated. From the initial velocity analysis, product inhibition and coenzyme binding studies, the reduction of befunolol was found to proceed through an ordered Bi Bi mechanism, in which beta-nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) binds to the enzyme firstly and NADP+ leaves lastly. NADPH bound to the free enzyme at a molar ratio of 1:1. Furthermore, the result of dead-end inhibition by Cibacron blue F3GA, a nucleotide analogue which binds to many enzymes, was consistent with the ordered Bi Bi mechanism for the enzyme. PMID- 2186875 TI - Presence of a dipeptidyl aminopeptidase III in Saccharomyces cerevisiae. AB - The soluble fraction of a cell extract of Saccharomyces cerevisiae was found to contain hydrolytic activity toward arginyl-arginyl-beta-naphthylamide (Arg-Arg beta NA). Most of the contaminating Arg-beta NA hydrolysis activity was removed by diethylaminoethyl (DEAE)-cellulose column chromatography and the enzyme was partially purified. It is very similar in various properties to mammalian dipeptidyl aminopeptidase III (DAP III), although it differs slightly in some respects. PMID- 2186876 TI - Lignified natural products as potential medicinal resources. I. Potentiation of hemolytic plaque-forming cell production in mice. AB - We have found that water-soluble extracts of lignified natural products are strong potentiaters of hemolytic plaque-forming cell production in mice. Apparently, the active components involved belong to a lignin family. Consequently, study of medicinal potential, especially immunopotentiating capacity, of lignified materials is important. PMID- 2186877 TI - Preparation of fluorescence-labeled and cross-linked subtilisin. AB - Streptomyces subtilisin inhibitor (SSI) is a protein characterized by both its potent inhibitory activity toward subtilisin and its structure, composed of two homologous subunits. It binds two molecules of subtilisin to form a tetrameric complex. Intermolecularly cross-linked subtilisin is expected to form a polymeric complex with SSI. This could provide a useful model of protein-protein association. Therefore, preparation of fluorescence-labeled and cross-linked subtilisin was carried out. PMID- 2186878 TI - Fluorescence labeled and cross-linked subtilisin: kinetic characteristics and binding to Streptomyces subtilisin inhibitor. AB - In the preceding paper, the preparation of fluorescent cross-linked subtilisin was described. In this paper we present the catalytic and binding properties of the modified enzyme. Kinetic analysis showed that the cross-linked dimeric subtilisin retained both catalytic activity and binding affinity toward synthetic substrates. These kinetic characteristics of the modified enzyme were nearly identical to those of the native enzyme. The modified enzyme also exhibited a specific interaction with Streptomyces subtilisin inhibitor (SSI) with 1 to 1 stoichiometry. The formation of a polymeric complex, which is the expected product with cross-linked subtilisin, was demonstrated. PMID- 2186879 TI - Inhibitory effects of galloylglucose on nicotinamide adenine dinucleotide dehydrogenases of the aerobic respiratory chain of Escherichia coli. AB - The effects of pentagalloylglucose (1,2,3,4,6-penta-O-galloyl-beta-D-glucose) on the aerobic electron transport system of Escherichia coli were studied. The activity of nicotineamide adenine dinucleotide (NADH) reductase was inhibited by pentagalloylglucose, but the activities of succinate dehydrogenase, D-lactate dehydrogenase, and ubiquinol-1 (Q1H2) oxidase were not susceptible to the inhibitor. Because the presence of two kinds of NADH dehydrogenase in respiratory chain of Escherichia coli has been reported, we examined the effect of galloylglucose independently on both NADH dehydrogenases. Pentagalloylglucose is potent and specific inhibitor of both NADH dehydrogenases. One of the NADH dehydrogenases (NADH dh II) is more sensitive to the inhibitor than the other (NADH dh I). PMID- 2186880 TI - Computer-aided diagnosis and decision-making in acute abdominal pain. PMID- 2186881 TI - Fulminant hepatic failure. PMID- 2186882 TI - Intestinal absorption of macromolecules and small particles. PMID- 2186883 TI - Diagnosis and treatment of fecal incontinence. PMID- 2186884 TI - Baker's cysts, pseudothrombophlebitis, pseudo-pseudothrombophlebitis: where do we stand? AB - The diagnostic approach and therapeutic attitudes to be assumed when facing the dilemma of deep vein thrombosis versus a complicated Baker's cyst remain unclear. We examined our own approach with 16 Baker's cysts [11 presenting with a "thrombophlebitis picture" (TP)] recently diagnosed in our services, and reviewed the literature. All of our patients had an underlying joint disorder and previous knee effusions. The diagnostic approach (i.e., the request or not for venography) was related to the specialty of the physician who saw the patient first. The results of the venography led to anticoagulation treatment in 5 of the 6 patients on whom it was performed, although these patients did not otherwise differ from those with a similar clinical picture in whom no venogram was obtained. Arthrograms performed early after onset of the TP were more likely to reveal cyst rupture. The recent literature does not mention serious venous complications (in particular, pulmonary embolism) in patients in whom only the cyst was treated, without knowledge of possible coexisting venous occlusions. The need to perform venography, the importance of the localisation of the occlusions and the therapeutic consequences are discussed and a proposal is made to study these patients in a systematic way in order to better understand the inter-relationship between complicated popliteal cysts and venous alterations, and to decide the best approach to assume in the future. PMID- 2186885 TI - Immune abnormalities in the pathogenesis of juvenile rheumatoid arthritis. AB - This article reviews the immune abnormalities involved in the pathogenesis of juvenile rheumatoid arthritis (JRA). We review both the humoral and cellular immune systems of children with JRA with emphasis on the possible role of these immune abnormalities in the pathogenesis of JRA. PMID- 2186886 TI - Studies using a canine model to investigate the cardiovascular abnormality of and potential therapies for septic shock. PMID- 2186888 TI - Bioactive factors in bone development and repair. A conference held in honor of Dr. Marshall R. Urist. Proceedings. PMID- 2186887 TI - Entamoeba histolytica: pathogenic mechanisms, human immune response, and vaccine development. PMID- 2186889 TI - The role of cells versus matrix in bone induction. AB - Earlier observations indicated that epithelial cells of urinary bladder, and transformed epithelial cells from human amnion (FL), epidermal carcinoma (HeLa), etc. can induce ectopic endochondral bone formation when implanted into the skeletal muscle of immunosuppressed or autologous animals. Such epithelial cells are associated with little matrix. Bone-inducing activity was also demonstrated in cultured osteosarcoma cells of murine and human origin or extracts thereof, and it is notable that these bone-inducing osteosarcoma cells grow in vitro with little matrix production. Finally, electron microscopy of in vitro cartilage induction showed that decalcified rodent bone that had been extensively extracted to remove cells still contained devitalized cells and cell fragments some of which made contact with inducible, cartilage-forming mesenchymal cells that had migrated in from cocultured muscle. Suggestions: These observations suggest that: 1) the bone-inducing agent(s) of both epithelial and mesenchymal cells may reside mostly in cells rather than matrix. Thus it may be premature to assume that bone "matrix" is the major source of bone-inducing agent in decalcified bone until the osteoinductive activity of residual bone cells has been assessed; and 2) that the osteoinductive agent, whether residing in epithelial cells or bone cells, may be the same or a similar factor operating through the same mechanism. PMID- 2186890 TI - Cartilage, bone and tooth induction during early embryonic mouse mandibular morphogenesis using serumless, chemically-defined medium. AB - Studies were designed to test the hypothesis that plasma- and serum-deprived embryonic cells and tissues in vitro are capable of producing growth regulating factors which augment cartilage, bone and tooth induction during mouse mandibular process development. Embryonic mouse first branchial arch-derived mandibular processes (E11-E12, Theiler stages 18-19) or cap stage molar tooth (M1) organs (E15-E16, Theiler stage 23) expressed morphogenesis, histogenesis and cytodifferentiation (e.g., Meckel's cartilage and mandibular bone) when cultured as explants in permissive serumless and chemically-defined BGJB medium for periods up to 31 days in vitro. Organ cultures of early mandibular process explants in serumless conditions showed DNA synthesis comparable to the time- and position-restricted patterns characteristic for control in vivo development. As a paradigm for embryonic cell expression of putative growth factors, sense and antisense oligodeoxynucleotide probes corresponding to amino acids 1070-1081 for preproEGF, and antibodies directed against amino acids 348-691 of preproEGF, were used to identify and localize mRNA transcripts and translation products. Our preliminary evidence suggests that odontogenic epithelial and ectomesenchyme cells produce EGF-like products during instructive phases of tooth development. We suggest that plasma- and serum-deprived cells and tissues in vitro produce autocrine and/or paracrine growth factors which mediate embryonic mandibular morphogenesis, histogenesis and cytodifferentiation. PMID- 2186891 TI - Neonatal cholestasis: an approach for the practicing pediatrician. PMID- 2186892 TI - Nuclear morphology and grading in tumours. PMID- 2186893 TI - Quantitation of the nucleus. PMID- 2186894 TI - Ultrastructural pathology of the nucleus. PMID- 2186895 TI - Flow cytometry in the quantitation of DNA aneuploidy and cell proliferation in human disease. PMID- 2186896 TI - Karyotypic analysis of solid tumors. PMID- 2186897 TI - Techniques and applications of in situ hybridisation. PMID- 2186898 TI - Nucleolar organiser regions. PMID- 2186899 TI - Multiple-dose kinetics in healthy volunteers and in vitro antimalarial activity of proguanil plus dapsone. AB - The multiple-dose kinetics of a daily dose of proguanil (200 mg) coadministered with dapsone (10 mg) was investigated in 6 healthy adult male volunteers. The kinetics of dapsone (DDS), monoacetyldapsone (MADDS), proguanil (PROG) and its active metabolite cycloguanil (CYCLO) were derived from plasma drug concentrations after the last maintenance dose. The following kinetic parameters (mean values) were estimated for DDS and PROG, respectively: maximum concentration (Cmax) = 285 and 151 ng/ml, minimum concentration (Cmin) = 125 and 31 ng/ml, elimination half-life (t1/2) = 23.3 and 18.3 h, plasma clearance (Cl) = 0.032 and 1.27 l/h/kg and apparent volume of distribution (Vss) = 1.05 and 33.32 l/kg. The Cmax, Cmin and t1/2 of CYCLO were 56 ng/ml, 17 ng/ml and 15.0 h, respectively. The antimalarial activity of the proguanil/dapsone combination was assessed in vitro by measuring the inhibition of re-invasion of two Plasmodium falciparum isolates grown in the presence of volunteers' sera. Both FC-27 [chloroquine (CQ)- and pyrimethamine (PYR)-sensitive] and K1 (CQ- and PYR resistant) isolates were completely inhibited by the drug combination at steady state concentrations. These findings suggest that the drug regimen may be effective against drug-resistant falciparum malaria. PMID- 2186900 TI - Immunocytochemical analysis of receptors for estrogen and progesterone in fine needle aspirates from human breast carcinomas. AB - Monoclonal antibodies were used for a preoperative analysis of estrogen receptors (ERs) and progesterone receptors (PgRs) in fine-needle aspirates from 44 primary human breast carcinomas. The semiquantitative receptor values obtained in cytologic specimens correlated well with those from enzyme immunoassay analysis on surgically removed tumor tissue (r = 0.74 for PgR; r = 0.75 for ER). Cytologic smears showed a heterogenous tumor cell distribution of ER and PgR in 29 and 23 cases, respectively. The results suggest that measurement of the ER and PgR in cytologic smears is an accurate and reliable technique that can be performed on a minimum amount of tissue. PMID- 2186901 TI - [Therapy of malignant lymphoma]. PMID- 2186902 TI - [Real time imaging with nuclear spin tomography. Snapshot-FLASH NMR imaging]. PMID- 2186903 TI - Quantitative structure-activity relationships for biodegradation. AB - Quantitative structure-activity relationships (QSARs) between biodegradation rates of organic compounds and chemical structure parameters are reviewed. Although a number of such relationships have been developed, they in general only apply to restricted ranges of compounds, limiting their value as predictors of biodegradation rates. For many of these classes of chemicals relationships have been reported with different structural descriptors, varying from macroscopic physical properties to molecular structure parameters. More information on the mechanism and rate-determining steps of biodegradation, which can lead to a better-founded choice of descriptors, and more biodegradation rate data are required to further develop QSARs for biodegradation. PMID- 2186904 TI - Application of bacterial growth kinetics to in vitro toxicity assessment of substituted phenols and anilines. AB - Bacterial growth kinetics were applied to determine toxicity of substituted phenols and anilines serving as model toxicants. The effects observed on Escherichia coli can be quantified reliably. Additional information is obtained about the onset, the duration, and the time course of the toxic action. For most compounds under study a uniform mode of toxicity was observed, but multihalogen and/or nitrosubstituted phenols differ in toxicity pattern. Possible reasons for the change in mechanism were examined. A comparison with published quantitative data for fish toxicity of halogenated phenols indicates good agreement with toxic effects observed in E. coli cultures. This may lead to the possibility of replacing the more costly, less stable fish test system by this simple and reliable in vitro test system. PMID- 2186905 TI - Protein kinase C and T cell activation. AB - Understanding the intracellular mechanisms by which binding of ligands, such as hormones and growth factors, to their specific receptors elicits the appropriate cellular response has long been a topic of great interest. Considerable excitement was generated when it was recognised that several receptor-ligand interactions operate via the hydrolysis of inositol phospholipids. This yields, at least, two 'second messengers', namely, inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], which causes the release of Ca2+ from intracellular stores, and 1,2-diacylglycerol (ac2Gro), which activates the serine/threonine-specific enzyme, protein kinase C(PKC), reviewed in [1] and [2]. The pertinent question that follows is, how do PKC activation and elevation of the intracellular Ca2+ concentration evoke cell responses? In this review, attention has been focused on PKC, and the consequences of its activation in resting human T cells. Evidence that PKC activity is, at least partially, responsible for activation of resting human T cells will be examined, and some of the more recent research investigating how PKC activation elicits this cell response will be described. PMID- 2186906 TI - Bacteriophage-associated glycan hydrolases specific for Escherichia coli capsular serotype K12. AB - Four bacteriophages were identified, which carry glycan hydrolases specific for the Escherichia coli K12 capsular polysaccharide. All these glycanases catalyze the hydrolysis of the alpha-L-rhamnosyl-1,5-beta-3-deoxy-D-manno-2-octulosonic acid linkage as demonstrated with a special thiobarbituric acid assay procedure, which discriminates between the C5 substituted and unsubstituted 3-deoxy-D-manno 2-octulosonic acid (dOclA). This assay, together with gel filtration, 1H-NMR and 13C-NMR spectroscopy showed that depolymerization led to the dimer of the K12 repeating unit, (,5-beta-dOcl1Ap-2,3-alpha-LRhap-1,2-alpha LRhap-1,)2, as the primary degradation product. The phages (phi 12-W, phi 12-S, phi 82-W1, phi 82 W2) were tested for their ability to infect Escherichia coli strains Su65-42 (O4:K12:H-) and CDC63-57 [O139:K82(12):H1]. phi 12-W and phi 12-S, respectively, infected strain Su65-42 only, phi 82-W2 CDC63-57 only, and phi 82-W1 both bacterial strains. These distinct host specificities cannot be explained by differences in the action of the glycanases, which depolymerize the capsules of both strains. PMID- 2186907 TI - Tissue distribution of avidin and streptavidin injected to mice. Effect of avidin carbohydrate, streptavidin truncation and exogenous biotin. AB - Radioionated avidin and streptavidin were characterized for their biodistribution and tissue association in Balb/c mice, in comparison to their interaction with cells in vitro. Binding of avidin to spleen and bone-marrow cells in vitro was up to 20-fold higher than that of streptavidin, but when tested in vivo avidin clearance from blood and tissues was considerably faster than that of streptavidin. Levels of avidin at 24 h after an intravenous injection were below 1% (of the injected dose/mass tissue) in most organs. Non-glycosylated avidin was similar in its biodistribution to native avidin. Native streptavidin exhibited higher and prolonged tissue association with 5-10% levels in lung, liver, spleen, kidney and blood, whereas its truncated form showed low tissue levels (1-3%) but a remarkably high affinity to the kidney (80%). Exogenous biotin did not affect streptavidin distribution in vivo but caused a 2-7-fold increase in the retention of avidin (but not non-glycodylated avidin) in some of the organs. PMID- 2186908 TI - DNA sequence of a citrate carrier of Klebsiella pneumoniae. AB - The citrate transport determinant of plasmid pES1 from Klebsiella pneumoniae [Schwarz E. and D. Oesterhelt (1985) EM BO J. 4, 1599-1603] has been subcloned in Escherichia coli DH1. The DNA sequence of a 1723-base fragment that codes for the citrate carrier has been determined and the gene product has been characterized with the T7 promoter system. The DNA fragment contains an open reading frame of 1332 base pairs and codes for a protein of 444 amino acids. The hydropathy profile suggests that the protein is very hydrophobic and contains 12 membrane spanning segments centered around a hydrophilic core. The gene for the citrate carrier has 66% similarity with a citrate carrier determinant from a naturally occurring plasmid responsible for secondary transport of citrate across the cytoplasmic membrane of E. coli. PMID- 2186909 TI - Prospective randomized study of once-daily versus thrice-daily netilmicin regimens in patients with intraabdominal infections. AB - One hundred and ninety-seven patients with intraabdominal infections were enrolled in a prospective randomized multicenter study of netilmicin administered once daily (n = 98) versus thrice daily (n = 99) in combination with tinidazole administered once daily. Randomization was achieved for the infection site, clinical severity score, daily and total netilmicin dose, and duration of treatment. The mean maximum peak and trough levels of netilmicin in serum were 21.1 and 1.3 mg/l respectively for once daily treated patients, and 10.0 and 2.3 mg/l for thrice daily treated patients (p less than 0.05 for both parameters). The clinical response did not differ between patients treated once daily and those treated thrice daily. Overall rates for clinical cure, improvement and failure of therapy were 77%, 17% and 6% respectively. No significant differences were found between once daily and thrice daily regimens in the occurrence of auditory, vestibular and renal toxicity, overall rates being 5%, 1% and 10% respectively. Impairment of renal function was significantly related to higher maximum netilmicin serum trough levels during therapy, a higher clinical severity score and advanced age. It is concluded that netilmicin given once daily is as effective and safe as the multiple dose regimen. However, monitoring of aminoglycoside serum through levels is still advisable, especially in the old and severely ill patient. PMID- 2186910 TI - Comparison of flagellum and sonicate antigens for serological diagnosis of Lyme borreliosis. AB - A sonicate antigen and two concentrations of a purified flagellum antigen of Borrelia burgdorferi were compared for serological diagnosis of Lyme borreliosis by an enzyme immunoassay (EIA). Generally, the higher concentration of flagellum antigen was found to be superior to the lower concentration, which was diluted eight times compared to the higher concentration. The diagnostic sensitivity for IgG antibody detection increased from 13% in the sonicate EIA to 31% in the best flagellum EIA assay (p = 0.01) in sera from patients with erythema migrans (n = 70), and from 34% to 55% (p = 0.01) in sera from patients with neuroborreliosis (n = 77). However, the sensitivity for IgG in sera from patients with acrodermatitis chronica atrophicans (n = 20) was high in both assays: 90% in the sonicate EIA compared to 95% in the flagellum EIA. Regarding IgM, there was no significant difference between the sensitivity of the assays in sera from any of the patient groups. The sensitivity values for IgM and IgG in cerebrospinal fluid (CSF) from patients with neuroborreliosis were also without significant differences. Sera and CSF from patients with meningitis/encephalitis of non Borrelia etiology (n = 35), multiple sclerosis (n = 9) or syphilis (n = 24), served as controls. The flagellum EIA showed a significantly improved specificity for IgG in CSF from controls with syphilis (p less than 0.01). It is concluded that purified Borrelia burgdorferi flagellum antigen is superior to a sonicate antigen, especially for serodiagnosis of the early stages of Lyme borreliosis. PMID- 2186911 TI - Value of detection of antibodies to Candida albicans germ tube in the diagnosis of systemic candidosis. AB - To test the value of detection of anti-Candida albicans germ tube antibodies by indirect immunofluorescence assay in the diagnosis of systemic candidosis, a retrospective study was done using 126 sera from 27 patients with presumptive systemic candidosis (13 immunocompromised), 165 sera from 45 patients with aspergillosis (29 immunocompromised), 35 sera from eight patients with cryptococcosis (6 immunocompromised), and 101 sera from 101 blood donors. While 21 of 27 patients with systemic candidosis (77.8%) had anti-germ tube antibodies, these antibodies were absent in all patients with cryptococcosis and in all blood donors. They were however detected in 5 of 45 patients with aspergillosis (11.1%). Ten of 13 (76.9%) immunocompromised patients with candidosis had anti germ tube antibodies; similar results were obtained in immunocompetent patients with candidosis (78.6%). The specificity was 96.8%, indicating a high degree of discrimination was possible between systemic candidosis and other invasive mycoses in the patients studied. Anti-germ tube responses did not appear to be significantly reduced in immunocompromised patients. PMID- 2186913 TI - Evaluation of the microplate hybridization method for rapid identification of Legionella species. AB - Rapid genetic identification of 23 Legionella species was performed using microdilution plate hybridization. When an isolate appeared to be a strain of the Legionella species, its DNA was quickly extracted, labelled with photobiotin and distributed to microdilution wells where 23 different DNAs had previously been immobilized. After hybridization for 90 min at 45 degrees C, the microdilution well which emitted the maximum fluorescence was determined. The criterion for interpreting results of this genetic identification method is given. PMID- 2186912 TI - Results of screening for verocytotoxin-producing Escherichia coli in faeces in Belgium. AB - During an 18-month period all stools submitted to a microbiology laboratory in Belgium for culture were screened for Verocytotoxin-producing Escherichia coli (VTEC) serotype O157. In the stool samples from 3940 patients, eight (0.2%) VTEC O157 strains were isolated, seven of which were O157:H7. Additional screening for other serotypes of VTEC in 332 selected stool samples yielded four more strains (serotypes O2:K1:H6, O111:H-, O117:K1:H7 and O"C70/86":H-). The 0.3% isolation rate for all VTEC was comparable to that for Shigella spp. Eight children under 30 months and two adults suffered from uncomplicated gastroenteritis. A 5-month old child and a 41-year-old woman presented with hemolytic uremic syndrome a few days after onset of a diarrheal episode. PMID- 2186914 TI - Comparison of the synthetic oligonucleotide gene probe and infant mouse bioassay for detection of enterotoxigenic Escherichia coli. AB - A commercial DNA/DNA hybridisation kit for the detection of Escherichia coli heat stable enterotoxin gene sequences was compared to the suckling mouse bioassay using 183 isolates of Escherichia coli from clinical specimens. The gene probe assay had a specificity of 99% and a sensitivity of 90.4% compared to the infant mouse method. Using the colony blot method of preparing the bacterial DNA and a hybridisation temperature of 50 degrees C optimal results were obtained. The gene probe method is not affected by the incubation conditions of the test organisms. It is technically straightforward and can be applied to large numbers of specimens with fewer logistic difficulties than with the bioassay. PMID- 2186915 TI - Proteus mirabilis as a cause of recurrent lung infection in a cystic fibrosis patient. PMID- 2186916 TI - Comparison of transport media for Bacteroides ureolyticus. PMID- 2186918 TI - Carotid artery stenosis--reassessment of the Doppler criteria. AB - Few previous studies of the accuracy of duplex Doppler in the assessment of carotid artery stenosis have looked at the accuracy in excluding disease in populations with a significant number of normal arteries. In addition, few studies have compared different criteria for stenosis. Duplex Doppler was used to evaluate the carotid arteries in 80 patients. Two well-described methods for analysing Doppler traces were used and the results were compared with those obtained from non-selective digital subtraction angiography. On the basis of these findings, the Doppler criteria used for carotid stenosis were redefined in terms of changes in peak velocity rather than Doppler frequency shift. Using these criteria, the sensitivity of Doppler in identifying carotid stenosis was 97% (98% sensitivity for greater than 50% stenosis) and specificity was increased from 84% to 93%. PMID- 2186917 TI - The effect of laxatives and enemas on the sonographic visibility of the pancreas. AB - Thirty-six patients were evaluated concerning the visibility of the pancreas under different conditions. One group (12 patients) was prepared with fasting for 4 hours, the second group (12 patients) was additionally given laxatives for one day prior to the examination together with a small enema (preparation for IVP). The third group (12 patients) received laxative treatment for 2 days (preparation for barium enema) but was otherwise treated in the same fashion as group 2. The study did not reveal any difference in visibility between the three groups thus indicating that routine preparation with 4 hours fasting alone can still be recommended when examining the upper part of the abdomen (except the gallbladder) with ultrasound. PMID- 2186919 TI - Radiographic features of hand and wrist surgery excluding arthroplasties. AB - The normal and abnormal radiographic appearances of various hand and wrist surgical procedures have been presented. It is hoped that increased familiarity with these procedures and their radiographic features will lead to more meaningful radiographic interpretations by consulting radiologists. PMID- 2186920 TI - Glial fibrillary acidic protein (GFAP) immunoreactivity in rabbit retina: effect of fixation. AB - The binding of monoclonal and polyclonal antibodies to glial fibrillary acidic protein (GFAP) antigenic sites in the rabbit retina was shown to be sensitive to aldehyde fixation. In chemically unfixed retina, the polyclonal anti-GFAP labeled Muller cells, astrocytes, and unidentified profiles in the outer plexiform layer; the monoclonal anti-GFAP labeled Muller cell endfeet and astrocytes only. The outer plexiform layer label with the polyclonal antibody was lost after fixation for 1 hr in 1% paraformaldehyde; elsewhere, the label was reduced. Fixation also reduced labeling by the monoclonal antibody. Such fixation sensitivity may underlie the different patterns reported for retinal GFAP immunoreactivity in the literature. PMID- 2186921 TI - Comparison of the hemopoietic growth factors produced during in vitro culture of murine and human fetal liver cells. AB - Under the conditions of in vitro liquid culture of murine fetal liver cells, some of the inoculated cells adhere to the flask surface. At optimum culture conditions, those adherent cells can survive and replicate for greater than 6 months in serial passages at intervals of 1 week. A similar adherent layer of cells on the flask surface occurred in a case with human fetal liver cells. These adherent cultured murine and human fetal liver cells can continuously release hemopoietic growth factors into the culture supernatant; among them spleen colony forming unit (CFU-S) proliferation stimulator, erythrocyte-granulocyte-macrophage colony-stimulating factor (EGM-CSF), burst-promoting factor (BPF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been identified. These factors are not only active in triggering resting CFU-S into cell cycling, but also in the proliferation and differentiation of hemopoietic progenitors of different lines. PMID- 2186922 TI - Progenitor cells in murine bone marrow stimulated by growth factors produced by the AF1-19T rat cell line. AB - The AF1-19T rat cell line has been found to produce an activity that acts synergistically with colony-stimulating factor 1 (CSF-1) to stimulate primitive high proliferative potential colony-forming cells (HPP-CFC) in mouse bone marrow (BM) that appear to be the same as those stimulated by the combination of 5637 cell-conditioned medium (CM) plus CSF-1 or recombinant human (rh) interleukin 1 (IL-1) plus recombinant murine (rm) interleukin 3 (IL-3) plus CSF-1. AF1-19T also produced granulocyte-macrophage colony-stimulating factor (GM-CSF), which could be separated from this synergistic activity by gel filtration followed by hydroxylapatite chromatography. Results obtained from the mouse thymocyte costimulation assay for IL-1, the hybridoma growth factor assay for interleukin 6 (IL-6), the ability to stimulate HPP-CFC, and the ability to block this stimulation with an antibody to murine IL-1 alpha suggest that the synergistic activity in AF1-19T-CM is probably a mixture of IL-1 activity and IL-6 or an IL-6 like activity. Other workers have described a progenitor cell population in mouse BM (CFU-A) that forms large colonies in response to AF1-19T-CM plus CSF-1 or GM CSF plus CSF-1. Experiments involving the kinetics of recovery after 5 fluorouracil treatment and generation of progenitors suggest that the GM-CSF-plus CSF-1-responsive progenitors, and hence CFU-A, are a more mature cell type than the more primitive HPP-CFC, responsive to 5637-cell-CM plus CSF-1 or rhIL-1 plus rmIL-3 plus CSF-1. PMID- 2186923 TI - Hematopoietic stem cell- and marrow stromal cell-specific requirements for gamma irradiation leukemogenesis in vitro. AB - The hematopoietic and stromal cell-specific properties of the cells involved in gamma irradiation leukemogenesis in vitro were defined. Cocultivation of clonal factor-dependent (FD), interleukin 3 (IL-3)-dependent cell lines 32D cl 3 or B6SUtA, or dual IL-3-/granulocyte-macrophage colony-stimulating factor (GM-CSF) dependent cell lines FDC-P1 or bg/bg d64 was carried out with clonal stromal cell lines D2XRII, GB1/6, +/+ 2.4, or Sld3. FD cell lines were added to control or 5000-cGy-irradiated plateau phase monolayer cultures of each stromal cell line, and parameters of stem cell engraftment and malignant transformation in vitro were quantitated. Cobblestone island formation by FD cells, cumulative production of nonadherent hematopoietic cells, and evolution of tumorigenic factor independent (FI) subclonal lines were quantitated over 5-8 weeks. There was no detectable evolution of FI sublines with 32D cl 3, B6SUtA, or bg/bg d64 cells cocultivated with control or irradiated Sld3 stromal cells. IL-3-dependent cell lines 32D cl 3 or B6SUtA formed small 10- to 49-cell cobblestone "clusters" at low frequency on control or irradiated D2XRII, showed limited proliferation for less than 1 week, and showed no detectable evolution of FI cell lines. Subclones of 32D cl 3 derived by transfection and expression of recombinant oncogenes v sis, or c-myc, or the epidermal growth factor receptor remained factor dependent and did not transform to factor independence after cocultivation with irradiated stromal cell lines. In contrast, cell line bg/bg d64, and each of seven subclonal lines of FDC-P1, including subclones selected for growth in GM-CSF, formed abundant cobblestone island colonies of greater than or equal to 50 cells on irradiated D2XRII stromal cells, produced non-adherent cells over 5-8 weeks, and showed evolution of tumorigenic FI subclonal lines. The data provide evidence for stable biological differences in both the hematopoietic and stromal cell components of the in vitro model of gamma irradiation leukemogenesis. PMID- 2186925 TI - Photosystem I reaction-centre proteins contain leucine zipper motifs. A proposed role in dimer formation. AB - The photosystem I (PS I) reaction-centre polypeptides, encoded by the psaA and psaB genes, are shown to contain several highly conserved leucine repeats, consisting of a leucine residue every seventh amino acid, similar to the leucine zipper motifs known to mediate DNA-binding polypeptide dimerisation. In each of the PSI reaction-centre subunits the leucine zipper motif precedes highly conserved cysteine residues which have been proposed to ligate the interpolypeptide [4Fe-4S] centre, Fx. We propose that PS I reaction-centre dimerisation and [4Fe-4S] centre formation are mediated through the leucine zipper. PMID- 2186924 TI - A RAS oncogene imparts growth factor independence to myeloid cells that abnormally regulate protein kinase C: a nonautocrine transformation pathway. AB - The factor-dependent cell line FDC-P1 has been utilized as a model of interleukin 3 (IL-3)-dependent myeloid cell proliferation. However, it has been recently observed that active phorbol esters (e.g., phorbol 12-myristate 13-acetate) may entirely replace IL-3 to promote its proliferation. These observations reveal abnormal regulation of protein kinase C (pkC) (absence of downregulation or overexpression). This property allowed a test of the hypothesis that the T24 RAS (codon 12) oncogene acts by constitutive and persistent pkC activation, driving proliferation. FDC-P1 cells were transfected by electroporation with the T24 RAS containing vector pAL 8, or with a control vector pSVX Zip Neo, and neomycin resistant clones were selected. Multiple RAS-transfectant clones were categorized for their growth factor requirement and incorporation of the 6.6-kb human mutant H-RAS genome. IL-3-independent clones had incorporated multiple (more than two) copies of the entire 6.6-kb RAS genome. The incorporation of multiple 6.6-kb RAS genomes was correlated with high-level p21 RAS expression. No evidence for autostimulatory growth factor production by clones containing the RAS oncogene was observed. Thus, acquisition of growth factor independence in myeloid cells by abundant expression of a RAS oncogene is linked, in part, to abnormal regulation of pkC, which acts as a collaborating oncogene. PMID- 2186926 TI - A nucleotide sequence in the translation start signal region is involved in heat shock-induced translation arrest in Escherichia coli. AB - In Escherichia coli synthesis of several proteins is transiently depressed upon heat shock treatment. A comparison of nucleotide sequences of the genes encoding these proteins revealed the occurrence of a consensus sequence, GAGGAA(N)3-6ATG, in their translation start signal region. To examine whether this sequence is involved in heat shock-induced depression of protein synthesis, DNA segments corresponding to this region of four of these genes, fusA, rpoB, glnS, and pheT, were synthesized, and each of them was fused in frame with the lacZ gene on the open reading frame vector pORF1. The effect of heat shock on the synthesis of beta-galactosidase encoded by these fused genes was then studied in E. coli. It was thus found that beta-galactosidase synthesis starting from the inserted translation start signal was arrested transiently upon temperature shift-up from 30 to 42 degrees C. I conclude that the heat shock-induced depression of gene expression is an event taking place at the initiation of translation. PMID- 2186927 TI - Effects of propeptide deletion on human renin secretion from mouse pituitary AtT 20 cells. AB - To study the role of the N-terminal propeptide in the secretory process of renin, mouse pituitary AtT-20 cells were transfected with expression plasmids of human preprorenin and a mutant deleted of its propeptide. The transfectant of the native construct secreted inactive prorenin and active renin, and renin secretion was stimulated by a secretagogue, 8-Br-cAMP. On the contrary, the transfectant of the deleted construct secreted only active renin, whose release was also stimulated by the secretagogue. The amount of renin molecule secreted from the latter transfectant was lower than that from the former one, although a significant amount of fully active renin could be produced. These results suggest that the propeptide plays an important role in the secretory process of renin, probably folding and/or stabilizing the renin molecule, but it does not contain the signal for intracellular sorting to target renin to secretory granules. PMID- 2186928 TI - Nerve growth factor stimulates protein kinase C translocation in PC12 cells. AB - The effect of nerve growth factor (NGF) on the activity and intracellular localization of protein kinase C (PKC) in pheochromocytoma PC12 cells was studied. By using immunoblotting, immunofluorescence method and phorbol ester binding, NGF was found to induce PKC translocation from the cytoplasm into the cell membrane. This process was accompanied by an increase in the protein kinase activity in the membrane fraction. Translocation was completely blocked by H-7, a protein kinase inhibitor potentiating the neurite-stimulating activity of NGF. PMID- 2186929 TI - A novel and sensitive assay for phospholipase D in intact cells. AB - A novel and sensitive assay for phospholipase D (PLD) that measures the incorporation of high specific activity [3H]butan-1-ol into [3H]phosphatidylbutanol has been developed. The assay has been used to measure PLD activation in human neutrophils and platelets. Both the chemotactic peptide fMet-Leu-Phe and opsonised-zymosan stimulated PLD in the human neutrophil. In the platelet, PLD was stimulated by thrombin and collagen but responses were small and only occurred at high agonist concentrations. This assay has a number of advantages over existing techniques and should be valuable for investigating PLD activation in a variety of isolated cells and possibly intact tissues. PMID- 2186930 TI - Surgical management of oral cancer. AB - Oral cancer remains a challenge and a frustration to the clinician. If treated when the tumor is small and localized, at least 70% of patients can be cured. Results of treatment of early and moderate-sized oral cancers are satisfactory and gratifying with minimal cosmetic and functional disability in contrast to the results following treatment of massive oral cancers. Clearly, the importance of early detection and appropriate treatment while the lesion is still low stage cannot be overemphasized. Alternative treatments, including laser vaporization/resection and photodynamic therapy, are being increasingly investigated and their indications and contraindications defined. Increased knowledge of the intricacies of chemotherapy and immunotherapy and their use as definitive treatment combined with advances in radiation therapy, including hyperfractionated irradiation and use of high-energy particles, may improve the overall outlook. Meanwhile, surgical treatment remains a mainstay in the management of many of these patients. We must emphasize the importance of early diagnosis and in those unfortunate patients with advanced disease further investigated the most efficient and effective combined modality treatment together with expeditious and effective reconstruction. Prevention is the ultimate goal, but as yet our societal motivation and energies are not directed on these lines. PMID- 2186931 TI - Maxillofacial prosthodontics. PMID- 2186932 TI - Radiation therapy for oral cavity cancer. AB - Radiation therapy, using both external beam and brachytherapy, is one of the mainstays of treatment for oral cavity cancers. For early lip, tongue, and floor of mouth lesions, radiation alone is highly effective and produces an excellent functional result. More advanced lesions are frequently treated with combined therapy or radiation alone with surgical salvage. Buccal mucosa and gingiva lesions are generally treated with surgery but can be managed by radiation therapy if they are early. More advanced lesions are treated by surgery plus postoperative radiation. Retromolar trigone lesions can be managed by radiation alone if they are small, but larger lesions are generally treated by combined therapy. Clearly, the goal of treatment of squamous cell cancer of the oral cavity is cure of the disease with optimal function results. These goals can be achieved only by cooperative interdisciplinary evaluation and management by the surgeons, radiation oncologists, and dentists involved in the care of these patients. PMID- 2186933 TI - Current concepts in the management of pain in the head and neck cancer patient. AB - The question arises as to the role of the dentist in the management of patients whose pain is of malignant disease origin. Dentists called on to provide treatment to these patients will often be asked their opinions on pain management. The purpose of this article is to familiarize the dentist with current trends in the treatment of pain of malignant origins. PMID- 2186934 TI - Prosthesis serviceability for acquired jaw defects. AB - Patients with acquired jaw defects treated with prostheses present variable prosthesis longevity due to variable factors that influence the tissue foundation anatomically and physiologically supporting the prosthesis. Prosthesis serviceability is unpredictable or limited in longevity. Multiple prostheses and sequential prostheses interrelated are often indicated to effectively rehabilitate patients with acquired jaw defects. PMID- 2186935 TI - Psychosocial considerations of the post-treatment of head and neck cancer patients. AB - The quality of life factor in the rehabilitation of head and neck cancer patients following surgery or other forms of treatment can be summarized as follows: 1. Because of serious functional disabilities, such as speech impairment and chewing swallowing difficulties, along with facial disfigurement, these individuals suffer the most problems of any type of cancer patient. 2. Without skilled rehabilitation intervention, their emotional, social, economic, and physical well being will be greatly impacted, perhaps for life. 3. With skilled intervention, building on patients' often amazing recuperative powers, successful rehabilitation to normal, or near-normal, levels comparative with their predisease condition may be achieved in a period between 6 months and a year. 4. Given continuing research and more generally available rehabilitation treatment, the prognosis is favorable. However, it would be less than honest to ignore one highly disquieting fact. Despite better treatment methods today, despite higher survival rates, we have not sufficiently changed our attitudes toward cancer rehabilitation. The same social stigma has stubbornly lingered, together with the fears of morbidity, uncertainty, and unpredictability. To help the patient recover old skills and pleasures, we must overcome these obstacles. To feel like a useful human being without any stigma attached, without undue fears and pressures but with a sense of being needed and wanted, that is what life is all about. All our rehabilitation efforts should be directed toward that goal, with the professional as well as the layman feeling optimism without feeling reservation and contagiously exuding it. To some extent, a real effort must be made to educate the professional as well as the layman to face the diagnosis of cancer without evasion and go forward from there. It is heartening that with support from both the government and private sectors there have been increasing numbers of major centers for rehabilitation established throughout the United States in recent years. The American Cancer Society, the National Cancer Institute, and the volunteers and philanthropists of America have been in the vanguard of this movement. With only some exceptions as noted above, the profession, including nurses as well as physicians, has responded to the call for more intensive rehabilitation efforts, as have social workers, family counselors, physical therapists, occupational therapists, speech pathologists, and other specialists. The challenge is enormous. Each patient has his or her own highly individual mind set and emotional characteristics and cultural, religious, economic, and class backgrounds, all of which will affect the response to the rehabilitation program.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2186936 TI - State-of-the-art materials used for maxillofacial prosthetic reconstruction. AB - The present state-of-the-art rests primarily on three general types of polymeric materials based on chemical configurations, that of polyacrylates, polydimethylsiloxane, and segmented block polyetherurethanes. Each of these types is currently prominent in a wide range of dental prosthodontics and surgical prosthetics with continued chemical variants emerging to attain enhanced biocompatibility for safety and effectiveness. However, owing to the disproportionally lower demand, the state-of-the-art for maxillofacial restorative prosthetics has not focused adequately on the specific array of the properties needed for the ideal prosthesis. To approach the ideality will require synthesizing new molecular configurations adjusted with component structures either as block copolymers or as intermediate oligomers. The synthetic effects must have a comprehensive plan of immediate assessments on terms of biocompatibility for safety to orofacial tissues and effective durability against all conceivable deterioration of the chemical structure. Above all, inasmuch as the skilled art and techniques of maxillofacial prosthetics is a custom-made specialty allied to the prosthodontics, the improved material for ideality should be readily amenable to molding by the well-established dental stone mold technology, for reasons of cost and simplicity. PMID- 2186937 TI - Osseointegration in maxillofacial prosthetics. AB - Intra-oral and extra-oral prosthetic restorations of acquired and developmental defects (oral, para-oral, and facial) have had a fundamental problem of inadequate stability and retention of the prostheses. Application of osseointegration in maxillofacial prosthetic reconstruction followed the positive results obtained by using osseointegrated implants for retaining and supporting maxillary and mandibular dental prostheses. The two case presentations are illustrative examples of the clinical application of osseointegrated implants for maxillofacial reconstructive prosthetic procedures. PMID- 2186938 TI - Orthodontic management of the congenital cleft palate patient. AB - Patients with cleft anomalies require extensive and prolonged treatment from birth to adulthood. These patients are subject to the scrutiny of many health disciplines during this comprehensive rehabilitation process. The orthodontist, who is intimately involved from the beginning, must achieve tooth alignment, arch symmetry, and establish a suitable functional occlusion that will provide allied disciplines with the appropriate foundation to optimize their treatment objectives. Each completed treatment phase should be sequential in manner, so as to facilitate and expedite the treatment goals of the other team member. To ensure the continuity of treatment and to satisfy the aesthetic, functional, and socio/psychologic requirements of each case, treatment must be coordinated and closely monitored by periodic team evaluations. PMID- 2186939 TI - Diagnosis and treatment planning for the surgical-orthodontic patient. AB - Contemporary orthognathic surgery has made it possible to reposition either or both jaws in one piece or as segmental osteotomies. This has provided the patient, who has a severe dentofacial problem, with the option of having all components of their malocclusion and facial aesthetic concerns addressed. The close collaboration between the orthodontist and the surgeon provides a comprehensive diagnosis and treatment plan to be generated. The goal of the presurgical phase of orthodontics is to remove the dental compensations and allow optimum surgical correction of the jaw discrepancy. A short phase of orthodontic treatment postoperatively is usually necessary to detail the final occlusion. A systematic approach to diagnosis and treatment planning is discussed in the context of the problem-oriented approach. The application of this approach is illustrated in a case report of the combined orthodontic-surgical treatment of a patient who benefited from a two-jaw surgical procedure with pre- and postoperative orthodontic treatment. The principles of presurgical orthodontic treatment are discussed and should avoid any counterproductive tooth movements that can be part of the surgical correction. Tooth movements done as part of the postoperative treatment should avoid compromising the surgical outcome. Illustrations of the cephalometric prediction tracing and its application to the diagnosis and treatment plan of the patient discussed in the case report is an important aspect in providing the dentofacial patient with a representation of the expected treatment outcome. PMID- 2186940 TI - Surgical-orthodontic correction of transverse maxillary deficiency. AB - A conservative osteotomy of the zygomaticomaxillary buttress in combination with a rapid palatal expansion appliance is a dependable technique for the treatment of horizontal maxillary deficiency in adults. This procedure has been used successfully in 56 patients in our series, but 17 patients (30 per cent) required a midpalatal osteotomy. In two patients, overexpansion was not achieved because of necrosis of the mucosa. In three other patients, expansion had to proceed at a slower pace because of mucosal ulceration. There have been no other complications. The procedure is indicated mainly in those patients with a horizontal deficiency who do not require subsequent surgery, but for some patients it may be the preliminary procedure. Twelve patients (21 per cent) had subsequent orthognathic surgery. Follow-up has been from 1 to 12 years and there has been no relapse. In our opinion, the zygomaticomaxillary buttress is the primary area of resistance to lateral movement of the maxilla by rapid maxillary expansion appliances. PMID- 2186941 TI - Cellular requirements for lymphokine secretion by rainbow trout Salmo gairdneri leucocytes. AB - The ability of different populations of rainbow trout blood leucocytes to produce MAF following stimulation with Con A/PMA was assessed by the amount of NBT reduction in target macrophages. The effect of varying lymphocyte or macrophage number on MAF production in the presence of a constant number of macrophages or lymphocytes respectively, showed that in both cases MAF activity initially increased with increasing cell number and then plateaued. Macrophages alone did not produce MAF whereas some MAF activity was produced by macrophage-depleted lymphocytes, although significantly lower than in the presence of macrophages. Separation of leucocytes into sIg- and sIg+ cells by panning showed that only sIg lymphocytes could produce MAF and that macrophages were necessary as accessory cells. These results support the contention that fish lymphocytes can be divided into sIg- T cells and sIg+ B cells. PMID- 2186942 TI - Ontogeny of the rat immune system: an immunohistochemical approach. PMID- 2186943 TI - Reexpression of alpha-smooth muscle actin isoform in cultured adult rat cardiomyocytes. AB - Expression of alpha-smooth muscle (sm) actin in regenerating adult cardiomyocytes in culture was investigated. No alpha-sm-actin could be detected in adult ventricular tissue or in newly dissociated rod-shaped cells, whereas a fraction of the polymorphic flattened out adult cardiac cells in culture did express the protein. Immunofluorescence studies revealed a characteristic staining pattern, suggesting the preferential presence of alpha-sm-actin in stress fiber-like structures, while newly formed myofibrils contained only little alpha-sm-actin isoprotein. Cell-cell contacts were resumed, but formation of new gap junctions, as revealed by microinjecting Lucifer yellow, was not dependent on alpha-sm-actin expression. The behavior corresponds to fetal cardiomyocytes either in tissue or as single cells in culture where expression of alpha-sm-actin can be observed. Such immunofluorescence staining patterns with corresponding immunoblot data can be expected when a return to a less differentiated, more fetal state of the adult cardiomyocyte in culture is assumed. The possible role of the alpha-sm-actin and alpha-sarcomeric actin isoforms during reformation of myofibrillar sarcomeres is discussed. PMID- 2186944 TI - Membrane skeleton protein 4.1 in developing Xenopus: expression in postmitotic cells of the retina. AB - Membrane skeleton protein 4.1 plays a key role in modulating the interactions of spectrin, actin, and integral membrane proteins in erythroid and nonerythroid cells. We have investigated its structure and expression during embryonic development of Xenopus laevis. An analysis of the complete 2758-nucleotide sequence and predicted translation of 801 amino acids (85.5 kDa) of X. laevis oocyte protein 4.1 reveals that, within overlapping regions, oocyte protein 4.1 is 74% identical to a composite amino acid sequence of human erythroid and lymphoid protein 4.1 and has an identity similar to that of amino acid motifs variably expressed in either human erythroid or lymphoid protein 4.1 S1 nuclease protection analysis demonstrates the presence of a single species of protein 4.1 transcript in embryos. Antibodies produced against X. laevis protein 4.1 fusion protein recognize two bands of 180 and 115 kDa on Western blots of X. laevis embryos and retina and, using immunocytochemical techniques, label the developing retina most intensely. In vitro transcription of a cDNA construct fully encoding X. laevis protein 4.1 yields a synthetic mRNA which, when translated in vitro, produces a polypeptide that comigrates on SDS-polyacrylamide gels with the 115 kDa form of embryos and retina. Protein 4.1 is found exclusively in photoreceptors following the terminal mitosis of retinal neurons. When retinal synaptogenesis is complete, protein 4.1 is also expressed in the inner retina. In adult amphibian retinas, protein 4.1 is detected in photoreceptors, bipolar cells, and ganglion cell axons. As these cell types have previously been shown to express spectrin, actin, and ankyrin, it is likely that the membrane skeleton of erythrocytes and retinal cells share functional similarities. PMID- 2186945 TI - Cleavage of A-CAM by endogenous proteinases in cultured lens cells and in developing chick embryos. AB - We describe two truncated forms of A-CAM (N-cadherin) and present evidence suggesting that both forms are proteolytically derived from the intact A-CAM molecule. The first is a membrane-bound fragment of A-CAM displaying an apparent molecular weight of 78 kDa. This polypeptide, containing the C-terminal portion of the protein, may be generated in cultured chicken lens cells, either by a short treatment with trypsin-EGTA, or by endogenous proteinase(s) during incubation in low Ca2+ medium. Immunofluorescent labeling of normal and EGTA treated cells indicated that the 78-kDa fragment is uniformly distributed over the cell surface. Moreover, staining of developing chick embryos with pairs of antibodies which distinguish the 78-kDa fragment from intact A-CAM indicated that, at early stages of sclerotome dissociation in developing somites, a truncated derivative of the molecule is generated. The second truncated form of A CAM is a 97-kDa polypeptide which is constitutively released by cultured lens cells into the culture medium in the presence of normal medium. We present evidence that the 97-kDa molecule is proteolytically derived from A-CAM by the action of an endogenous proteinase. We discuss possible mechanisms leading to the formation of these two truncated derivatives and their possible involvement in the physiological modulation of A-CAM-mediated interactions. PMID- 2186946 TI - Induction of the endogenous whey acidic protein (Wap) gene and a Wap-myc hybrid gene in primary murine mammary organoids. AB - In rodents, the whey acidic protein (Wap) is the major whey protein expressed in mammary glands in response to lactogenic hormones. The regulation of the Wap gene differs from that of other milk protein genes, with one consequence being that little or no Wap expression is detectable in cell culture. Here we describe the efficient in vitro induction of the Wap gene in mammary organoids isolated from midpregnant mice. Mammary organoids were isolated as intact epithelial subcomponents which retained the glandular microarchitecture. If organoids were cultured in contact with a monolayer of 3T3-L1 adipocytes, significant levels of Wap mRNA were induced upon hormonal stimulation, with the highest level of Wap mRNA being induced by a combination of hydrocortisone, prolactin, and insulin. Dissociation of the three-dimensional organization abrogated Wap inducibility. Organoids cultured on plastic or hydrated type I collagen did not transcribe Wap mRNA even after hormonal stimulation. Addition of hormones was required to maintain low levels of Wap mRNA in organoids cultured on reconstituted basement membrane, however, Wap mRNA was not induced. Organoid-adipocyte interactions as well as cell-cell interactions inherent in the structure of organoids promote hormone-dependent Wap mRNA expression. In order to study the Wap promoter region in vitro, we cocultured organoids from transgenic mice harboring a chimeric Wap myc gene with 3T3-L1 adipocytes. Lactogenic hormones induced the Wap-myc transgene in vitro. The kinetics of induction were similar for both the transgene and the endogenous Wap gene indicating that the 2.5-kb regulatory Wap region present in the hybrid gene contains the sequence elements required for hormone induced gene expression in vitro. PMID- 2186947 TI - Comparison between ectoderm-conditioned medium and fibronectin in their effects on chondrogenesis by limb bud mesenchymal cells. AB - Limb bud ectoderm inhibits chondrogenesis by limb bud mesenchymal cells cultured at high density or on collagen gels. This ectodermal antichondrogenic influence has been postulated to function in vivo in regulating the spatial patterning of cartilage and soft connective tissue in the limb. We have developed a method for preparing ectoderm-conditioned medium containing antichondrogenic activity. Using a simple bioassay, we have investigated some characteristics of the ectodermal products and their effects on limb bud mesenchymal cells. Inhibition of chondrogenesis by ectoderm-conditioned medium was tested on limb bud mesenchymal cells cultured on collagen gels. The antichondrogenic influence involves enhanced cell spreading and is alleviated by agents, such as cytochalasin D, that induce cell rounding. Fibronectin resembles ectoderm-conditioned medium in its ability to inhibit chondrogenesis and promote cell spreading in collagen gel cultures of limb bud mesenchymal cells. However, Western blot analysis shows that the antichondrogenic activity of ectoderm-conditioned medium is not due to fibronectin in the medium. Peptides related to the fibronectin cell-binding domain block the antichondrogenic effect of fibronectin, but not that of ectoderm conditioned medium. On the other hand, an antibody to an integrin, as well as heparan sulfate, alleviates the antichondrogenic effects of both fibronectin and ectoderm-conditioned medium. The antichondrogenic effect of ectoderm-conditioned medium may be mediated by an integrin and by a cell surface heparan sulfate proteoglycan, but it does not depend directly upon fibronectin-mediated cell spreading. PMID- 2186948 TI - Open spina bifida: outcome for a complete cohort treated unselectively and followed into adulthood. AB - Between 1963 and 1970, 117 consecutive cases of open spina bifida were treated unselectively from birth, following a full neurological examination. The author reviews the outcome 16 to 20 years later. 48 died before their sixteenth birthday. Of the 69 survivors, 60 had had a shunt inserted and two were blind following shunt dysfunction; 22 were mentally retarded (IQ less than 80); 35 were wheelchair-dependent; 52 were incontinent, and 32 of these continued to need help with its management; nine weighed greater than 75 kg; one-third of both sexes had a precocious puberty; three had insulin-dependent diabetes; 12 continued to need anticonvulsant drugs; 32 had suffered from pressure sores; 33 were unable to live without help or supervision and only 17 were capable of open employment. These findings demonstrate the wide range of disabilities implied by the diagnosis of open spina bifida. The neurological findings recorded at birth were reflected in the mortality and disability of the survivors. The sensory level represented a yardstick for predicting the likely range of handicap into adult life, provided no additional impairment resulted from serious complications: such damage occurred in seven of the survivors. PMID- 2186949 TI - Effect of acute Yersinia enterocolitica infection on small intestinal ultrastructure. AB - The purpose of this study was to assess the jejunal and ileal brush border injury caused by Yersinia enterocolitica and to correlate these alterations with functional abnormalities. Weanling rabbits infected with 10(10) organisms of a human pathogenic Y. enterocolitica strain were compared with control and pair fed, sham-treated animals. On day 6, infection resulted in a diffuse decrease in brush border enzyme activities in the small intestine and villus atrophy and crypt hyperplasia in the ileum. By day 14, ileal architecture and jejunal disaccharidases had returned to normal, but enzyme abnormalities persisted in the ileum. Ultrastructural studies showed decreased brush border surface area in the jejunum and ileum on day 6 and in the ileum on day 14 of infection. Abnormalities of brush border function caused by infection correlated with the changes in microvillus surface area. In pair-fed animals on day 6, brush border surface area was slightly decreased in the ileum but increased in the jejunum, suggesting that the brush border injury resulted from infection rather than from malnutrition alone. The findings indicate that Y. enterocolitica inflicts a diffuse brush border injury that is in keeping with the generalized defect in brush border enzyme activity and transport function. PMID- 2186950 TI - Sequential protooncogene expression during regeneration in rat stomach. AB - Cellular protooncogenes such as c-myc and c-Ha-ras may play important roles in the control of regeneration of the stomach. In this study, in situ hybridization histochemistry and immunohistochemistry were used to determine how these protooncogenes and the corresponding oncoproteins are expressed at the cellular level during gastric regeneration after mucosal injuries caused by indomethacin. In addition, cells in the S-phase were immunohistochemically detected by means of 5-bromo-2'-deoxyuridine incorporation. Expression of the c-myc gene was localized to nuclei and reached a maximum at 3 h, and that of the c-Ha-ras gene was localized to cytoplasm with a peak at 6-12 h after treatment on the mucous neck, parietal, chief, and enterochromaffinlike cells around the lesions. The distribution of cells in the S-phase roughly coincided with that of cells in which expression of the protooncogenes was detected. In conclusion, various types of gastric mucosal cells participated in the sequential regulated expression of cellular protooncogenes during regeneration of the rat stomach. PMID- 2186951 TI - A report of three multiclinic trials evaluating arbaprostil in arthritic patients with ASA/NSAID gastric mucosal damage. The Upjohn Company Arbaprostil ASA/NSAID Gastric Mucosal Damage Treatment Study Groups. AB - Three randomized, placebo-controlled multiclinic trials involving arbaprostil dosages of (a) 10 micrograms; (b) 25 micrograms; and (c) 10, 25, or 50 micrograms orally for 4 wk in patients older than 18 yr with rheumatoid arthritis or osteoarthritis who had endoscopically documented nonsteroidal antiinflammatory drug-associated gastric mucosal damage were conducted in the United States. All patients continued taking the nonsteroidal antiinflammatory drugs and were reendoscoped after 4 wk of therapy. Success at that time was defined as complete resolution of all gastric mucosal damage. Six hundred fifty-eight patients were enrolled in the three trials. Significantly more patients experienced healing in the arbaprostil treatment groups in all trials compared with those who received placebo. The healing rates in the various trials were 68% and 32% (10 micrograms vs. placebo; p = 0.007); 77% and 23% (25 micrograms vs. placebo; p less than 0.001); and 52%, 46%, 35%, and 16% (50, 25, and 10 micrograms vs. placebo; p less than 0.001, less than 0.001, and 0.002, respectively). Diarrhea, mostly of a mild nature, was the only arbaprostil-associated side effect and was found with the 25 and 50-microgram dosages (33% and 59%, respectively). No exacerbation of arthritis signs or symptoms was found. Arbaprostil at doses with varying effects on gastric acid secretion (25 and 50 micrograms) was documented in these trials to be an effective and safe agent for healing gastric mucosal damage associated with aspirin or other nonsteroidal antiinflammatory drugs in patients with either rheumatoid arthritis or osteoarthritis without adversely affecting joint symptomatology. PMID- 2186952 TI - Intestinal anaphylaxis in the rat. Effect of chronic antigen exposure. AB - The effect of chronic dietary antigen challenge on the intestine was examined in sensitized rats. Three groups of Hooded-Lister rats were studied: animals sensitized to egg albumin; sham-sensitized animals; and unmanipulated controls. In sensitized rats, serum immunoglobulin E titers to egg albumin were greater than or equal to 1:64, whereas control and pair-fed rats showed no response. Sensitized rats received egg albumin 1 mg/ml in drinking water and rat chow ad libitum. Pair-fed animals also received egg albumin but were pair-fed with sensitized animals. Controls received water and rat chow ad libitum. Chronic antigen challenge resulted in reduced food intake and weight gain in sensitized animals. When the rats were killed after 9 days of antigen exposure, proximal intestine from experimental animals showed decreased disaccharidase activity, brush-border microvillus surface, area, and villus height. Crypt depth and enterocyte migration rate were increased. Mucosal mast cell involvement was suggested by mast cell proliferation, evidence of mast cell degranulation, and increased serum rat mast cell protease II levels. At the time of death, only sensitized jejunum demonstrated an increase in short-circuit current in Ussing chambers in response to antigen challenge. The findings indicate that chronic antigen exposure leads to intestinal injury, reduced food intake, and diminished weight gain. PMID- 2186953 TI - Observer variability in echo-Doppler measurements of portal flow in cirrhotic patients and normal volunteers. AB - The intraobserver and interobserver variability in measuring the portal vein flow by the echo-Doppler technique was evaluated in a blind controlled study. A total of 22 cirrhotic patients and 14 normal volunteers were examined by two skilled operators using duplex Doppler within a period of 1-3 mo (6 cirrhotics and 7 normal volunteers by both observers). Area, mean velocity, and flow were measured (4 measurements: A, B on day 1; C, D on day 2). The intraclass correlation coefficient was used to assess both the statistical and clinical significance of intraobserver and interobserver agreement for the measurements of these three parameters. The level of intraobserver agreement for each parameter on normal subjects and cirrhotics was obtained from the two measurements on the same day and from the two measurements at the same time on consecutive days. Overall agreement between the four measurements was also calculated. Levels of interobserver agreement were obtained by calculating separately the intraclass correlation coefficient from each of the four pairs by measurements made on the same subject by the two observers over the same period of 2 days. The coefficient of variation was also used to compare the variability in these measurements. Overall, intraobserver agreement on normal subjects varied from good to excellent for observer 1, and from fair to good for observer 2. On cirrhotic patients, observer 1 was excellent at all times for all parameters. Observer 2 had lower intraclass correlation coefficient values, especially for velocity on consecutive days. For the best of the two observers on the portal flow, the coefficient of variation in cirrhotic patients ranged from 2%-30% with a mean +/- SEM of 12% +/- 4%. No acceptable interobserver agreement was found between the two observers in either of the two samples of subjects. These results support the use of this technique mainly for the determination of rapid and large changes in portal hemodynamics within a short period of time. The technique seems to have low precision in monitoring chronic changes in portal hemodynamics. PMID- 2186954 TI - Gallbladder stone fragments in feces after biliary extracorporeal shock-wave lithotripsy. AB - All stools passed on the first 3 days after extracorporeal shock-wave lithotripsy of gallbladder stones in 21 patients were collected and examined for the presence of stone fragments. A total of 555 fragments varying in number per patient (4-69) and in size (maximum diameters from 0.5-8.0 mm) were recovered by sieving aqueous suspensions of the feces. All 482 fragments less than or equal to 3.0 mm left the biliary tract without any clinical symptoms, as did the three largest fragments with maximum diameters of 7.0-8.0 mm and almost all of the 70 fragments measuring 3.5-5.0 mm. During the observation period, four episodes of biliary complaints were recorded in three patients in whom fragments with maximum diameters of 3.5 5.0 mm were found. The only chemical abnormality was a temporary elevation of lipase activity to twice the normal range in 1 case. All fragments were identified as gallbladder stones by infrared spectroscopy on the basis of their (varyingly high) cholesterol content. By macroscopic criteria, most of the fragments were from mixed stones; therefore, provided there is a functioning gallbladder and sufficiently fine fragmentation, successful extracorporeal shock wave lithotripsy does not seem to be limited to pure cholesterol stones. PMID- 2186955 TI - Isolation and characterization of peptides from the protein core of bovine gallbladder mucin. AB - Gallbladder mucin may promote cholesterol gallstone formation by accelerating cholesterol monohydrate crystal nucleation in supersaturated bile. In this study, peptides were isolated from the mucin protein core by protease digestion and molecular-sieve high-performance liquid chromatography. Tryptic peptides were purified by anion exchange or reverse-phase high-performance liquid chromatography, and amino acid compositions were determined. Tryptic peptides were (a) nonglycosylated, (b) selectively enriched in serine, glutamic acid plus glutamine, and glycine, and (c) depleted in threonine and proline compared with native gallbladder mucin. Bilirubin derivatized with Woodward's reagent K covalently bound to purified mucin. Tryptic digestion of the mucin-bilirubin complex yielded low-molecular-weight nonglycosylated peptides with covalently bound bilirubin. These data indicate that the mucin protein core contains at least two distinct domains. One domain is rich in threonine and proline and contains the majority of covalently bound carbohydrate. A second domain, possibly internally located, is nonglycosylated, enriched in serine, glutamic acid plus glutamine, and glycine, and binds hydrophobic ligands such as bilirubin and 1 anilino-8-naphthalene sulfonate. Hydrophobic domains on the mucin protein core may contribute to the pathogenesis of cholesterol cholelithiasis. PMID- 2186956 TI - Effect of pancreatic proteases on plasma cholecystokinin, secretin, and pancreatic exocrine secretion in response to sodium oleate. AB - The effect of pancreatic proteases or juice on the sodium oleate-stimulated pancreatic secretion and plasma concentrations of secretin and cholecystokinin in anesthetized rats was investigated. Each rat received sodium oleate in a dose of 0.12 mmol.h-1 via a duodenal tube. Sodium oleate infusion significantly increased pancreatic secretion (volume and protein output) compared with the saline given the control group. The increase in pancreatic secretion paralleled significant elevations of plasma concentrations of secretin and cholecystokinin. To determine a possible role of pancreatic proteases on the responses induced by sodium oleate, saline, chymotrypsin, and trypsin, a combination of chymotrypsin and trypsin or pancreatic juice was infused into the duodenum. The pancreatic secretion was significantly reduced by pancreatic proteases or pancreatic juice, and the reduction paralleled the decreases in plasma concentrations of the two hormones. These agents suppressed both pancreatic secretion and plasma hormone levels in the following order of magnitude: (pancreatic juice or chymotrypsin + trypsin) greater than (trypsin) greater than (chymotrypsin). The reduction of pancreatic secretion by pancreatic proteases was reversed by intravenous administration of secretin and cholecystokinin in physiological doses. It is concluded that negative-feedback regulation of pancreatic secretion is operative in the intestinal phase in rats and that both secretin and cholecystokinin are involved in the regulation. PMID- 2186958 TI - Salmonid pituitary gonadotrophs. I. Distinct cellular distributions of two gonadotropins, GTH I and GTH II. AB - Using antisera specific for the beta subunits of two distinct coho salmon gonadotropins, GTH I and GTH II, an immunocytochemical study of rainbow trout and Atlantic salmon pituitaries was done. Cells which immunostained with anti-GTH I beta were distributed in the periphery of the glandular cords of the proximal pars distalis (PPD), in close association with somatotrophs. On the other hand, cells immunostained with anti-GTH II beta were located in the central parts of the glandular cords of the PPD. Neither the GTH I-producing nor the GTH II producing cells stained with antisera against chum salmon growth hormone or the beta subunit of human thyroid-stimulating hormone. Moreover, GTH I and GTH II were localized in distinctly different cells. In no case was colocalization of these GTHs in the same cell observed. Finally, it was concluded that classification of GTH cells as globular and vesicular forms does not reflect the type of hormone produced by the cell, but may reflect differences in the physiological conditions of the cells. PMID- 2186957 TI - Growth effects of regulatory peptides on human pancreatic cancer lines PANC-1 and MIA PaCa-2. AB - Several studies have reported effects of gastrointestinal regulatory peptides on growth of experimentally induced pancreatic neoplasms and human cancer cell lines. The growth of human pancreatic cancer lines PANC-1 and MIA PaCa-2 was characterized in vitro, and the effects of cholecystokinin, bombesin, insulin, epidermal growth factor, secretin, vasoactive intestinal peptide, and somatostatin were determined. Fetal bovine serum was required for initiation of growth in both cell lines. Growth effects of peptides were determined by incubating cells with peptides in serum-free medium after a 72-h preincubation in 10% serum-supplemented medium alone. Epidermal growth factor (3.4 x 10(-9) M) and insulin (10(-6) M) significantly (p less than 0.001) increased growth of both cell lines as determined by increases in deoxyribonucleic acid and protein. Bombesin, secretin, vasoactive intestinal peptide, and somatostatin (all 10(-8) M) did not affect growth of either cell line. Neither cholecystokinin-8 nor [Thr4, Nle7] cholecystokinin-9 altered growth in concentrations from 10(-12)-10( 6) M. Anchorage-dependent clonogenic growth of both cell lines was also not altered by cholecystokinin-8. Cholecystokinin added to cultures was degraded by separate effects of serum and cells. Addition of cholecystokinin-8 to cultures every 8 h maintained cholecystokinin levels but did not alter cell growth. These data support roles for epidermal growth factor and insulin as growth factors for human pancreatic cancer cell lines. PMID- 2186959 TI - Salmonid pituitary gonadotrophs. II. Ontogeny of GTH I and GTH II cells in the rainbow trout (Salmo gairdneri irideus). AB - Immunocytochemistry of rainbow trout pituitary gonadotrophs (GTH I- and GTH II producing cells) during gametogenesis was investigated. GTH I and GTH II were found in distinctly different cells in all stages of reproductive development that were examined. Only GTH I cells were present in trout prior to puberty. GTH II appeared in addition to GTH I coincident with the onset of vitellogenesis and spermatogenesis. Both GTH I and GTH II cells were found in trout at the time of final reproductive maturation, although the number of GTH II cells was greater than that of GTH I cells. These data indicate that GTH I and GTH II are localized in separate cells in the trout pituitary throughout gametogenesis, and that synthesis of GTH I and GTH II varies during reproductive development. PMID- 2186960 TI - Effects of GnRH-associated peptide and its component peptides on prolactin secretion from the tilapia pituitary in vitro. AB - The rostral pars distalis (RPD), containing mainly prolactin (PRL)-secreting cells, of the pituitary from immature and mature tilapia was incubated for 16 hr at 27 degrees in hypoosmotic medium (300 mOsm/kg) in the presence (10(-8) and 10( 11) M) or absence of the human GnRH-associated peptide (GAP) molecule, a potent PRL-inhibiting factor in mammals (Nikolics et al., Nature (London) 316, 511, 1985), and of a series of its component peptides. The release of the two forms of PRL in tilapia into the medium was measured by sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by densitometry. The variability inherent in this method was normalized by calculating PRL release as the percentage of the total hormone present in both tissue and medium. Newly synthesized PRL was detected by incorporation of [35S]methionine, introduced into the culture medium, by the PRL molecules. In immature tilapia, GAP inhibited the release of total PRL while stimulating the release of newly synthesized large PRL. Among the GAP fragments tested, 28-36 was the fragment that most significantly affected PRL secretion. Both concentrations of fragment 28-36 stimulated the release of newly synthesized PRL from immature rostral pars distalis (RPDs). This stimulation appears to be dependent on the osmotic pressure of the medium since this fragment did not affect PRL secretion in hyperosmotic medium (340 mOsm/kg). Fragment 38-49 inhibited total PRL release from mature RPDs. Fragment 51-66 stimulated the release of total PRL from mature RPDs. Examination of tissue and medium values in densitometric units after incubation with fragments 28-36 and 51-66 indicated that while the tissue content of PRL was decreased, the medium content of PRL was not affected. This suggests that fragments 28-36 and 51-66, in opposition to the situation found when the data are expressed as percentage release of PRL, may not stimulate PRL release but may instead decrease the tissue content of PRL. These results suggest that the entire human GAP molecule, as well as some of its fragments, may have direct effects on the PRL cells in the tilapia pituitary. PMID- 2186961 TI - Chronological appearance of the different hypophysial hormones in the pituitary of sea bass larvae (Dicentrarchus labrax) during their early development: an immunocytochemical demonstration. AB - Antisera raised against chum salmon prolactin (PRL), rainbow trout growth hormone (GH), mammalian adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), and luteinizing hormone (LH) were used to study the chronological appearance of immunoreactivity for PRL, GH, ACTH, TSH, LH, and melanocyte stimulating hormone (MSH) in the pituitary of sea bass larvae (Dicentrarchus labrax) during the first 26 days after hatching. The anti-ACTH gives positive immunostaining in the ACTH cells as well as in the MSH cells; however, the two cell types can easily be distinguished by their different localization in the pituitary: ACTH in the rostral pars distalis, MSH in the pars intermedia. The first day after hatching cells immunoreactive for TSH, GH and ACTH could already be noticed, ACTH reacted strong in the pars intermedia but very weak in the rostral pars distalis. Cells immunopositive for PRL became visible between Days 9 and 15. With anti-LH, no positive reaction could be obtained during the first 26 days after hatching. PMID- 2186962 TI - Evolution of the Pittsburgh studies of the epidemiology of insulin-dependent diabetes mellitus. Pittsburgh Diabetes Epidemiology and Etiology Research Group. AB - The Pittsburgh project evaluating the epidemiology and etiology of insulin dependent diabetes mellitus (IDDM) is currently one of the large ongoing studies of childhood diabetes. This paper traces the evolution of the project, from the initial basic epidemiologic approach in the early 1980s, to the current thrust where complex molecular genetic approaches are being incorporated into population based research. The epidemiology models employed in the Pittsburgh project are similar to those that could be used in many areas of chronic disease research. The integration of immunogenetics into epidemiology produces a powerful approach for understanding the complex interaction of host susceptibility and environmental agents that contribute to the development of IDDM. PMID- 2186963 TI - Farmer's lung: thermophilic actinomycetes as a source of "farmer's lung hay" antigen. 1963. AB - Mouldy hay was produced in the laboratory by sterilising good hay, inoculating with aqueous suspensions of microorganisms, and incubating at 40 degrees or 60 degrees C. Extracts were tested for presence of farmer's lung hay (F.L.H.) antigen by agar-gel double-diffusion and immunoelectrophoresis tests against sixteen to twenty sera from patients with farmer's lung. F.L.H. antigen developed in hay after: (1) inoculating with mixed microbial suspensions from antigenically active hay; (2) inoculation with mixed suspensions of pure cultures of thermophilic actinomycetes, after raising the pH of the hay to 70 either by prior inoculation with fungi or by infiltration with ammonia vapour; and (3) inoculation at pH 70 with pure cultures of Thermopolyspora polyspora or with Micromonospora vulgaris. F.L.H. antigen did not develop in hay after inoculation with fungi only, or with six other actinomycetes tested, or after prior heating (though some sera reacted to fungal antigens in all these extracts). T. polyspora is the richest source yet found of F.L.H. antigen, and inhalation of an extract by affected subjects produces some of the features of farmer's lung. Pure cultures can produce F.L.H. antigen on artificial media without hay. Spores and mycelium are rich in F.L.H. antigen, and inhalation of the spores may play a part in farmer's lung disease. Other antigens relevant to farmer's lung may be found in other actinomycetes, not yet cultured. PMID- 2186964 TI - Through the centuries with food and drink, for better or worse. V. PMID- 2186965 TI - Carboxy-terminal determinants of intracellular protein degradation. AB - Using the amino-terminal domain of lambda repressor as a model system, we show that residues in an unstructured region at the extreme carboxyl terminus of the protein are important for determining its proteolytic susceptibility in Escherichia coli. Nonpolar amino acids are destabilizing when placed at the 5 carboxy-terminal residue positions, whereas charged and polar residues are stabilizing. The stabilizing effect of a single charged residue is greatest when it is at the terminal position and diminishes with increasing distance from the carboxyl terminus. The position of destabilizing sequences with respect to the free carboxyl terminus is important for their effect, but their distance from the folded portion of the protein is not important. Specific degradation of proteins with nonpolar carboxyl termini has been reconstituted in vitro using a partially pure, soluble fraction. This degradation is not ATP-dependent. Moreover, amino terminal domain variants with nonpolar carboxy-terminal residues are still rapidly degraded in strains that are deficient in proteolysis of abnormal proteins. These data suggest that the degradation of amino-terminal domain variants with nonpolar carboxy-terminal residues involves proteolytic components distinct from those known to be important for the turnover of unfolded proteins in E. coli. PMID- 2186966 TI - Subunits shared by eukaryotic nuclear RNA polymerases. AB - RNA polymerases I, II, and III share three subunits that are immunologically and biochemically indistinguishable. The Saccharomyces cerevisiae genes that encode these subunits (RPB5, RPB6, and RPB8) were isolated and sequenced, and their transcriptional start sites were deduced. RPB5 encodes a 25-kD protein, RPB6, an 18-kD protein, and RPB8, a 16-kD protein. These genes are single copy, reside on different chromosomes, and are essential for viability. The fact that the genes are single copy, corroborates previous evidence suggesting that each of the common subunits is identical in RNA polymerases I, II, and III. Furthermore, immunoprecipitation of RPB6 coprecipitates proteins whose sizes are consistent with RNA polymerase I, II, and III subunits. Sequence similarity between the yeast RPB5 protein and a previously characterized human RNA polymerase subunit demonstrates that the common subunits of the nuclear RNA polymerases are well conserved among eukaryotes. The presence of these conserved and essential subunits in all three nuclear RNA polymerases and the absence of recognizable sequence motifs for DNA and nucleoside triphosphate-binding indicate that the common subunits do not have a catalytic role but are important for a function shared by the RNA polymerases such as transcriptional efficiency, nuclear localization, enzyme stability, or coordinate regulation of rRNA, mRNA, and tRNA synthesis. PMID- 2186968 TI - DNA looping in cellular repression of transcription of the galactose operon. AB - Communication between distant DNA sites is a central feature of many DNA transactions. Negative regulation of the galactose (gal) operon of Escherichia coli requires repressor binding to two operator sites located on opposite sides of the promoter. The proposed mechanism for regulation involves binding of the repressor to both operator sites, followed by a protein-protein association that loops the intervening promoter DNA (double occupancy plus association). To assess these requirements in vivo, we have previously converted gal operator sites to lac and shown that both operator sites must be occupied by the homologous repressor protein (Lac or Gal) for negative regulation of the gal operon. We have now addressed more directly the need for protein-protein association by the use of the converted operator sites and a mutant Lac repressor defective in association of the DNA-binding dimers. We have compared the biological and biochemical activity of two Lac repressors: the wild-type (tetramer) I+ form, in which the DNA-binding dimer units are tightly associated; and the mutant Iadi repressor, in which the dimer units do not associate effectively. The I+ repressor is an efficient negative regulator of the gal operon in vivo, but the Iadi mutant is an ineffective repressor. Purified I+ repressor efficiently forms DNA loops between operator sites that we have visualized by electron microscopy; the Iadi repressor fails to form DNA loops, although the protein binds effectively to both operator sites. From the clear correlation between looping in vitro and repression in vivo, we conclude that regulation of the gal operon depends on the association of repressor proteins bound to the two operator sites.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2186967 TI - Rapid and transient expression of Ets2 in mature macrophages following stimulation with cMGF, LPS, and PKC activators. AB - We reported previously that Ets2 is expressed in normal and transformed macrophages. We show here that the expression of both c-ets-2 mRNA proteins is induced rapidly and transiently in chicken nondividing bone marrow-derived macrophages but not in E26-transformed myeloblasts in response to chicken myelomonocytic growth factor (cMGF), an avian hematopoietic growth factor required for survival, proliferation, and colony formation of avian myeloid cells. c-ets-2 expression is also rapidly induced in chicken bone marrow-derived macrophages, human monocytes, and mouse peritoneal macrophages in response to LPS and/or PKC activators. The rapid induction of Ets2 after treatment of chicken bone marrow-derived macrophages by cMGF is blunted after down-regulation or inactivation of PKC, suggesting a role of PKC in the cMGF-induced signal transduction pathway. Because Ets2 is localized in the nucleus of macrophages and binds to DNA in vitro, the kinetics of its expression suggest a role for Ets2 in the transduction within the nucleus of specific signals received at the cell membrane and involved in securing the survival and/or the development of functional competence of these cells. PMID- 2186969 TI - Metastatic thyroid carcinoma masquerading as lacrimal gland tumor. AB - A 56-year-old woman presented with orbital signs and symptoms suggestive of lacrimal gland tumor. An excised biopsy specimen was obtained and showed glandular tissue, which could be confused with lacrimal gland acini. Closer microscopic examination and immunohistochemical studies revealed a metastatic tumor of thyroid gland origin. Initially, there was no identifiable nodule in the thyroid, but 3 months later a thyroid nodule was found by ultrasound and radioisotope scan. The histopathologic appearance of the thyroid nodule was similar to that found in the orbit. This case demonstrates the usefulness of immunohistochemistry in establishing a diagnosis when the microscopic appearance is inconclusive. PMID- 2186970 TI - Cone dystrophy and supernormal dark-adapted b-waves in the electroretinogram. AB - A male patient suffering from cone dystrophy was followed over 9 years. In addition to the typical clinical and electrophysiologic signs, supernormal b waves were found in the dark-adapted electroretinogram. Our case is compared with 12 similar patients described in the literature. Our patient differed from the other patients in the following aspects: he was male and had a congenital stationary disease with a small pigment epithelial scar in the left eye only and no other fundus changes up to the age of 22 years. He did not complain of night blindness. The dark-adapted electroretinogram of our patient showed a normal b wave threshold with increased b-wave amplitudes and markedly prolonged b-wave latencies and implicit times. This combination of signs has not been reported to date in any other patient and points towards a postreceptoral defect of the interneuronal connection. PMID- 2186971 TI - Oxygen and diabetic eye disease. AB - In 1956, Wise suggested that retinal hypoxia stimulated retinal neovascularization in the ischemic proliferative retinopathies. Although not directly proven, this theory is strongly supported by a wealth of circumstantial information. Two treatment modalities, vitrectomy and panretinal photocoagulation, have been shown to be effective against retinal neovascularization in diabetics. Both of these treatment modalities improve retinal oxygenation, and we propose that this is the mechanism through which they halt retinal neovascularization. The mechanism for improving retinal oxygenation is different for the two treatment modalities. In the case of panretinal photocoagulation, the new oxygen supply comes from the choroid through the laser scar in the outer retina. In the case of vitrectomy, it comes from the vitreous cavity itself, but the end result is the same. We have expanded Wise's hypothesis to include these two treatment modalities, which were not known at the time of Wise's original paper. PMID- 2186972 TI - Histochemical studies on hyaluronic acid in the developing human retina. AB - Changes in the distribution of hyaluronic acid in the developing human retina were investigated histochemically with alcian blue staining and the Streptomyces hyaluronidase digestion method using 56 human embryos and fetuses ranging from 5 to 41 weeks of gestational age. Hyaluronic acid was first detected in the inner layer of the retina at 12 weeks. The site of accumulation extended towards the outer layer by 20 weeks. At the neonatal stage, longitudinal fibers, possibly the processes of Muller cells, were proved to contain hyaluronic acid. These findings suggest that Muller cells produce hyaluronic acid transiently from 12 weeks' gestation to the neonatal stage. PMID- 2186974 TI - Immunocytochemical localisation of collagens (I-V) in the human iris. AB - In this study we investigated the distribution of collagen types I-V in the human iris at the fine-structural level using cryoultramicrotomy and London Resin White plastic embedding. Collagen type I was shown to be present in the basement membrane of iris vessels, in contrast to type III, which was absent; both types I and III were present in the iris stroma. Collagen type IV was a major component of basement membranes of vascular cells, myoepithelial cells, fibroblasts and epithelial cells. Types II and V were absent. Both cryo and plastic embedding techniques produced closely comparable results. PMID- 2186975 TI - New technique to demonstrate the network of blood capillaries of the human retina in their three-dimensional arrangement. AB - A method is presented that demonstrates the whole network of the blood capillaries of the human retina, making it possible (using a dark-field microscope at high magnification) to view the three-dimensional arrangement of this network in different planes by moving the drive of the microscope. The basic principle includes filling the vascular system with oxygen in statu nascendi by injection of H2O2 into the vitreous body of the intact eye and achieving fixation of the retinal tissue by application of a mixture of H2O2 and ethanol, and rendering the dry and flat retinal preparation transparent by soaking it in a specially prepared resin. The retinal vessels are made visible in an optically empty dark field by diffraction of light in a gas-filled specimen. This method allows preparation of the human retinal vasculature in simply enucleated eyes without cannulation of the central retinal artery and, therefore, it may be appropriate to support pathological and anatomical investigations. PMID- 2186973 TI - Thrombin stimulates the proliferation of human retinal glial cells. AB - Retinal glial cells may play a role in most of the proliferative retinopathies. Although glial cell proliferation is a frequent event in retinal pathobiology, no specific mitogens for human retinal glial cells are known. Using cultured retinal glial cells obtained from postmortem adult human eyes, we found that thrombin stimulates glial cell proliferation in a dose-dependent manner with a half maximal concentration of 100 ng/ml (0.4 U/ml). Thus, thrombin may be a plasma derived mitogen capable of stimulating retinal glial cells to proliferate when there is a breakdown of the blood-retinal barrier. We also observed that this proliferative response of retinal glia requires more than 6 h of continuous exposure to thrombin. This finding suggests that a thorough wash-out of a thrombin-containing infusate and/or the rapid inactivation of this molecule would prevent thrombin form exacerbating a proliferative disorder of the retina. PMID- 2186977 TI - Vasodilatation associated with hepatocellular disease: relation to functional organ failure. PMID- 2186976 TI - Antimalarial activity of the ethanol/alcohol oxidase system in vitro. AB - Among other macrophage secretory products, H2O2 plays an important role in the host's defense against malaria (Wozencraft et al., Infect. Immun., 43, 664, (1984]. In our in vitro studies on the human malaria parasite Plasmodium falciparum, hydrogen peroxide was produced by the alcohol oxidase-catalyzed reaction ethanol + O2----acetaldehyde + H2O2 (EC 1.1.3.13). At concentrations of 8.7 mM (= 0.5%) ethanol and 0.1 U alcohol oxidase per ml culture, more than 95% of the parasites were irreversibly damaged. Acetaldehyde was found to be parasiticidal per se--probably by releasing immature forms of P. falciparum from erythrocytes--but CH3CHO concentrations as high as 90 mM were required for complete elimination of the parasites. Ethanol (less than 20 mM) or alcohol oxidase alone had no significant effect on parasite viability. As discussed, the ethanol/alcohol oxidase system might be of interest as a potential chemotherapeutic principle, especially since metabolism and pharmacology of the substrates and products are well understood. PMID- 2186978 TI - Intraoperative abdominal ultrasound. PMID- 2186979 TI - Histamine containing endocrine cells in the human stomach. AB - Histamine and chromogranin A-immunoreactive cells were studied in the mucosa of the human stomach. Cells reacting to both histamine and chromogranin A-antibodies (histamine containing endocrine cells), were demonstrated by double immunostaining and found to be restricted to the oxyntic mucosa. Histamine containing cells that did not stain with chromogranin A-antibodies were numerous throughout the stomach. Of the histamine immunoreactive cells in the oxyntic gland area 22% reacted with antibodies against chromogranin A. Histamine containing endocrine cells constituted 44% of the total number of endocrine cells in the oxyntic mucosa. These findings suggest that the histamine containing endocrine cells in the human stomach are identical with the so called enterochromaffin like cells. PMID- 2186980 TI - Inhibition of nocturnal acidity is important but not essential for duodenal ulcer healing. AB - We have determined the relative importance of day and night time gastric acid inhibition for duodenal ulcer healing by comparing the anti-ulcer efficacy of a single morning with that of a single bedtime dose of ranitidine. One hundred and thirty patients with active duodenal ulcer were randomly assigned to a double blind therapy with ranitidine 300 mg at 8 am or the same dose at 10 pm for up to eight weeks. The antisecretory effects of these regimens were also assessed by 24 h intragastric pH monitoring in 18 of these patients. At four weeks ulcers had healed in 41/61 (67%) of patients taking the morning dose and in 47/63 (75%) of those receiving the nocturnal dose (95% CI for the difference -0.09 +0.25; p ns). At eight weeks, the corresponding healing rates were 82% and 85.5%, respectively (95% CI for the difference -0.11 +0.17; p ns). Both treatments were significantly superior to placebo in raising 24 h intragastric pH, although the effects of the morning dose were of shorter duration than those of the nocturnal dose. These findings suggest that suppression of nocturnal acidity is important but not essential to promote healing of duodenal ulcers; a prolonged period of acid inhibition during the day (as obtained with a single large morning dose of H2 blockers) may be equally effective. PMID- 2186981 TI - Kinetics of enteroendocrine cells with implications for their origin: a study of the cholecystokinin and gastrin subpopulations combining tritiated thymidine labelling with immunocytochemistry in the mouse. AB - Evidence for a common endodermal stem cell has been derived from kinetic studies in mouse small intestine which indicate that the turnover characteristics of endocrine cells are similar to those of other cell lineages (columnar and goblet cells). We have used continuous tritiated thymidine labelling and peptide immunocytochemistry on resin embedded semithin sections, a combination of techniques which have not been used before in the small intestine. Our data show that the turnover time for endocrine cells in the small intestine is 10 days, considerably longer than the four days suggested by previous studies, although for columnar and mucous cell lineages, turnover rates are similar to the published literature. In the stomach, the turnover time was very slow indeed (of the order of 45-60 days). These results show that endocrine cells do not share turnover characteristics with the other cell types and suggest that they constitute a kinetically distinct cell population independent of the other cell lineages. These data are not consistent with a common stem cell origin for gut endocrine cells. PMID- 2186982 TI - Effect of colloidal bismuth subcitrate on symptoms and gastric histology in non ulcer dyspepsia. A double blind placebo controlled study. AB - The aim of this study was to determine the effect of colloidal bismuth subcitrate (De Nol) on symptoms and gastric histology in patients with non-ulcer dyspepsia. In a single centre trial, patients with food related upper abdominal pain not caused by ulcer disease were randomised to receive one tablet of colloidal bismuth subcitrate or matching placebo four times daily for eight weeks. Seventy three patients were entered and 51 completed the trial: 28 patients in the colloidal bismuth subcitrate group and 23 in the placebo group. Overall there was no difference between the two groups in terms of symptom relief. Among patients with histological gastritis (n = 23), however, those who took colloidal bismuth subcitrate used fewer antacid tablets (for three of four fortnightly periods) and were more likely to become asymptomatic (eight of 11 v three of 12, p less than 0.05); their gastritis was more likely to resolve (five of 10 v 0 of 12, p less than 0.025) and their gastric biopsies more likely to become negative for Helicobacter like organisms (eight of nine v 0 of 12, p less than 0.001) when compared with patients taking placebo. In contrast, patients who did not have gastritis in their index biopsies (n = 28) fared similarly whether they received colloidal bismuth subcitrate or placebo. Our results indicate that the administration of colloidal bismuth subcitrate benefited non-ulcer dyspepsia patients with gastritis but had no effect on those without. PMID- 2186983 TI - Biochemical and functional characteristics of integrins: a new family of adhesive receptors present in hematopoietic cells. PMID- 2186984 TI - Autologous bone marrow transplantation in acute lymphoblastic leukemia: biological and clinical aspects. AB - The purpose of this review is to assess the current status of autologous bone marrow transplantation in acute lymphoblastic leukemia. In the first part of the review the biological aspects of minimal residual disease are discussed and in the second part the most recent clinical results analyzed. Only the studies that contained adequate response and survival data were selected for analysis, including peer-reviewed articles, book chapters and proceedings of international meetings. The most current or complete references were used for series reported more than once. PMID- 2186985 TI - [The Tsuge suture. Experimental and clinical experiences]. AB - Microangiographic studies in the flexor profundus tendon of the rabbit show the relationship between the gaps in tendon-stumps and tendon adhesions of the suture line. Reasonably low average gaps could be achieved by the Kirchmayr/Kessler-type and by the Tsuge-type of tendon suture, which have both the same principle of fixation: solid anchorage in a set distance from the suture line and axial traction of the thread. Clinical cases show the advantages of the Tsuge suture for flat and oval tendons especially for the flexor superficialis tendon and the extensor apparatus. For distal fixation of tendon sutures to bone, pulley and tendon insertion it has also proven to be a reliable and simple technique. PMID- 2186986 TI - [Compression neuropathy of the median nerve at the wrist joint caused by chondroma]. AB - The case is reported of a 75-year old patient with diabetes, who suffered from a typical carpal tunnel syndrome, which was diagnosed by a neurologist. On the X rays of hand and wrist there were no pathological findings. A small, clinically almost inapparent induration at the palmar and radial side of the wrist was found. Ultrasonography and CT-scan showed a tumor with compression of the median nerve. At operation the authors excised a tumor which on histological investigation was compatible with a soft tissue chondroma. Full recovery followed local excision with decompression of the median nerve. Soft tissue chondromas localised to the hand and wrist are extremely rare. A few cases have been described in the literature which led to a nerve compression. PMID- 2186987 TI - [Growth, maturation and environment]. AB - Using as example the secular trend, relations between growth, maturation and environment are discussed. This phenomenon is characterized by an increase of the average height and an acceleration of growth velocity and maturation. The increase is acquired mainly in the early childhood. The secular trend has been modified by local and socio-economic differences in the frequency of malnutrition and morbidity. It is now minimal in countries with high standards of health and hygiene. It can appear or can be accelerated in all developing countries with progress in child-health, especially in early childhood. A negative trend can be expected in every country, where child-health deteriorates for a long time. PMID- 2186988 TI - [Clinical significance of magnesium. 1: Distribution in the organism, evaluation of current supply]. AB - The most important compartments of Mg metabolism are described: Bone Mg stores correlate closely with serum Mg, which latter depends mainly on intestinal absorption and excretion, predominantly via the kidneys. Since intracellular Mg is mainly bound, the overall intracellular Mg concentration depends largely on the amount of available ligands such as ATP. Serum Mg reflects the Mg content of bone stores. The frequency at which hyper- or hypomagnesemia occurs depends largely on the precision with which the normal range is established. Recommendations for the sampling of serum are made. PMID- 2186989 TI - [Psychotherapy procedures in chronic pain]. AB - Psychotherapeutic possibilities of treating chronic pain are employed in two different ways: Firstly in the form of psychotherapy in patients whose strategies for coping with pain and/or pain genesis can be described in terms of psychopathological categories; secondly in the form of pain-coping training, which is generally indicated in the presence of chronic pain, in particular that which is traditionally termed organic. With respect to their effectiveness in achieving, in the first place, mood change, and in the assessment of symptoms, the individual procedures have been well tested. The question as to differential indication, which can most readily be applied to the use of biofeedback, remains largely unanswered. PMID- 2186990 TI - [Clinical aspects of functional cardiovascular disorders]. AB - Functional cardiovascular disorders are a very common clinical picture. Patients with such disorders account for a not inconsiderable percentage of the patients of a doctor's practice. In the present article, major aspects of the symptomatology and pathogenesis of importance for the differential diagnosis and treatment, are discussed from a psychosomatic point of view. PMID- 2186991 TI - [Inhalation therapy with selective beta 2-sympathomimetic drugs. Effect of pirbuterol administered via the Autohaler and salbutamol administered via the Diskhaler in obstructive respiratory tract disease]. AB - The therapeutic success of salbutamol inhalation with the powder inhalator (Diskhaler) and of pirbuterol with an inhalation-triggered metered aerosol (Autohaler) was determined by comparing the degrees of bronchodilation in 13 patients suffering from chronic obstructive airways disease. Rt and IGV were determined by whole-body plethysmography and FEV1, peak flow and MEF50 by spirometry, and pulse rates were also measured. On average, Rt values decreased by 40 per cent; the other lung function parameters responded correspondingly. Duration of action extended to 4 hours after dosage. Pulse rates and lung functions measured after administration of the products did not differ, either. In such studies as this, whole-body plethysmographic results are superior to those obtained by spirometry. PMID- 2186992 TI - [Review of recent empirical studies of the classification, pathogenesis and therapy of anxiety disorders]. AB - Beginning with the eighties, a paradigm-change concerning anxiety disorders has taken place in considerable parts of psychiatry. Anxiety disorders are no longer regarded as consequences of conflicts and ineffective defences or as concomitants of other psychiatric disorders but rather as disorders of their own. This resulted in a modified outlook on anxiety disorders focusing on the acute panic attack (Panic disorder) instead of focusing on chronic anxiety (Anxiety neurosis). This paper reviews recent empirical studies concerning classification, pathogenesis, and therapy of anxiety disorders, i.e. after introduction of the concept of Panic disorder. Epidemiological studies could demonstrate that in western countries anxiety disorders account for the most frequent psychiatric disorders with prevalence rates of 2.0% to 4.7%. Panic disorders show prevalence rates of 0.4% to 1.1%. Results of recent follow-up studies indicate a favorable course for outpatients and an unfavorable course for inpatients with anxiety disorders. Family studies reported on positive familial loading for Panic disorder but not for Agoraphobia and Generalized anxiety disorder. A twin study found higher concordance rates for panic attacks and Agoraphobias in monozygotic twins than in dizygotic twins. Pharmacological provocation studies with lactate infusion, CO2-inhalation, and administration of Caffeine, Yohimbine, Isoproterenol showed a higher vulnerability of patients with Panic Disorder as compared to healthy controls. However, all studies display methodological short comings and could be interpreted differently as to the concept of a biologically determined vulnerability. Provocation studies using inverse Benzodiazepine agonists dealt only with healthy probands. Whereas life events play a rather unimportant role fur the pathogenesis of anxiety disorders, recent studies point to the influence of cognitive processes and personality variables for the pathogenesis of anxiety disorders. Concerning treatment of anxiety disorders and especially of panic disorders, pharmacological studies as well as studies of behavioural therapy indicate very good results for acute treatment and good results for behavioural therapy with respect to one to four year follow-up studies. Recently, combined drug and psychotherapy gains growing interest. Conclusions are drawn with respect to the usefulness of the new classification, i.e. after the introduction of Panic disorder as a diagnostic category, and references are given for further research strategies. PMID- 2186993 TI - The pulmonary pathologic manifestations of the CREST syndrome. AB - This report evaluates the histopathologic alterations of a series of 17 patients with the CREST syndrome and relates these alterations to clinical and functional abnormalities. Histologic abnormalities were classified into the following four distinct patterns: pulmonary vascular changes, primarily intimal fibroelastosis, associated with and without pulmonary hypertension; a pattern of fibrosis indistinguishable from usual interstitital pneumonia (UIP); small airways disease; and mixtures of these three patterns. Five patients (29%) had clinical and morphologic pulmonary hypertension, while five others showed mild reductions in diffusing capacity, presumably due to vascular compromise. Five patients had UIP-like interstitial fibrosis, with vascular alterations and restrictive lung disease. Only one patient had small airways disease exclusively. Concentric fibrointimal proliferation and occlusion of arterioles was worse in patients with clinical pulmonary hypertension and interstitial fibrosis of the UIP type, and was not always associated with pulmonary fibrosis. Twenty-one percent of patients developed primary lung carcinomas. The CREST syndrome is unique in the spectrum of pulmonary alterations seen in progressive systemic sclerosis for its high incidence of clinical pulmonary hypertension and propensity for the development of pulmonary carcinomas. PMID- 2186994 TI - Primary adrenocortical micronodular dysplasia: enzyme histochemical and ultrastructural studies of two cases with a review of the literature. AB - The adrenal glands from two patients with primary adrenocortical micronodular dysplasia (PAMD) were studied (no. 1, a 23-year-old man with cardiac myxomas and sarcoidosis; no. 2, a 16-year-old girl). The PAMD cells showed intense activity of 3 beta-hydroxysteroid dehydrogenase (3 beta DH), succinate DH, glucose-6 phosphate DH, alkaline phosphatase (AlPase), and other DHs and lysosomal hydrolases, giving a characteristic staining pattern. The staining patterns correlated well with ultrastructural findings. The larger adrenals (no. 1: 16.6 g) were associated with larger black nodules and internodular cortex (INC) with fairly well-retained enzyme activities, and contained cell clusters and single cells with intense AlPase activity with the appearance of PAMD nodules in the buds. The smaller adrenals (no. 2: 5.4 g) were associated with smaller black/yellow nodules, and had INC with weaker enzyme activity. Analysis of descriptions of INC in 25 previously reported cases revealed that the larger adrenals (more than 10 g) had less atrophic INC than the smaller ones. The characteristic enzyme pattern in PAMD cells explains the paradox that PAMD adrenals smaller than normal can cause Cushing's syndrome, and may be useful for investigating neoplastic and non-neoplastic counterparts in other adrenal lesions. The relationship between PAMD cells and INC is not simply one of autonomy versus atrophy, and both cell types may be stimulated by a certain common trophic factor. Thus, PAMD belongs to the category of hyperplasia. PMID- 2186996 TI - Microdissection of banded human chromosomes. AB - Physical dissection of metaphase chromosomes is the most straightforward approach for the isolation of DNA sequences from specific chromosome regions. However, conventional microdissection techniques are too crude and inefficient for analysis of the human genome. Here we describe a technique for the precise dissection of single bands from GTG-banded chromosomes. Cells from normal amniotic fluid cell cultures are harvested by the pipette method. Microdissection is performed on an inverted microscope (magnification 1250X) with the help of extended siliconized glass needles and an electronically controlled micromanipulator. Enzymatic amplification of the dissected DNA allows the construction of band-specific DNA libraries from as few as 20 dissected chromosome fragments. PMID- 2186997 TI - ECG data compression techniques--a unified approach. AB - A broad spectrum of techniques for electrocardiogram (ECG) data compression have been proposed during the last three decades. Such techniques have been vital in reducing the digital ECG data volume for storage and transmission. These techniques are essential to a wide variety of applications ranging from diagnostic to ambulatory ECG's. Due to the diverse procedures that have been employed, comparison of ECG compression methods is a major problem. Present evaluation methods preclude any direct comparison among existing ECG compression techniques. The main purpose of this paper is to address this issue and to establish a unified view of ECG compression techniques. ECG data compression schemes are presented in two major groups: direct data compression and transformation methods. The direct data compression techniques are: ECG differential pulse code modulation and entropy coding, AZTEC, Turning-point, CORTES, Fan and SAPA algorithms, peak-picking, and cycle-to-cycle compression methods. The transformation methods briefly presented, include: Fourier, Walsh, and K-L transforms. The theoretical basis behind the direct ECG data compression schemes are presented and classified into three categories: tolerance-comparison compression, differential pulse code modulation (DPCM), and entropy coding methods. The paper concludes with the presentation of a framework for evaluation and comparison of ECG compression schemes. PMID- 2186995 TI - Evolution of the Simiiformes and the phylogeny of human chromosomes. AB - This paper is based on the results of Primate chromosome studies obtained using high resolution techniques in our and other laboratories. We discuss the origin and the evolution of the chromosomes in the human karyotype and the time in evolution of the Simiiformes when they acquired their present morphology. Our results indicate that the chromosomes that underwent a higher number of reorganizations during the evolution of the Simiiformes coincide with the chromosomes most often implicated in human chromosome pathology. We describe the main reorganizations that took place during Primate evolution. Centromere activation and inactivation and heterochromatin changes are discussed as mechanisms of chromosome evolution. PMID- 2186998 TI - Isolation and purification of murine monoclonal IgG1 employing specific immuno affinity chromatography. AB - Studies were performed to determine if murine monoclonal immunoglobulin G1 (IgG1) could be purified from ascites fluid employing specific immuno-affinity chromatography. Murine polyclonal IgG was first removed from the ascites fluid by passage over immobilized protein A at pH 7.0. Analysis of the ascites fluid after this procedure revealed that murine monoclonal IgG1 did not bind to the protein A under the conditions employed. Additional analyses revealed that murine polyclonal IgG bound to and could be eluted from the immobilized protein A. Subsequent passage of the ascites fluid through an immunoadsorbent containing sheep antibody to murine monoclonal IgG1 revealed that the murine monoclonal IgG1 isotype was specifically removed. Analyses of the immunoglobulin eluted from the immuno-affinity matrix revealed the presence of murine monoclonal IgG1 with purities equal to or greater than 95%. PMID- 2186999 TI - Use of anti-cholera toxin IgA-secreting hybridoma cells for the elaboration of an antigen-specific IgA-ELISPOT-assay. AB - Hybridoma anti-cholera toxin (CT) IgA-secreting cells, because of their monoclonal character, were used to establish and optimize an ELISPOT-assay for CT specific IgA-secreting cells. The use of hybridoma cells easily and quickly allowed the elaboration of a sensitive, specific and reproducible ELISPOT-assay, which was successfully applied to enumerate intestinal lamina propria lymphoid cells secreting anti-CT IgA in mice immunized twice intraintestinally with CT. Monoclonal antibody-secreting hybridoma cells, if available against a given antigen, are suggested as ideal cell suspensions to elaborate new ELISPOT-assays to study antibody responses at the cellular level. PMID- 2187000 TI - Is it possible to prevent obesity? AB - No-one is immune to obesity, but those with a family history of obesity, or those who have in the past lost weight, are particularly liable to excessive weight gain. There is no useful way of identifying that portion of the population which is at particularly high risk of obesity so that preventive measures can be focussed on that subgroup. Prevention of obesity therefore requires early detection and treatment of excessive weight gain. For various reasons the age range 5-12 years is particularly advantageous for correcting obesity in children, since normal weight-for-height can be achieved without actual weight loss. Obesity in adults is to a small extent genetically determined, but weight loss is always possible with the appropriate dietary treatment. The most difficult problem in preventing adult obesity is to ensure that excess weight which has been lost is not regained. Reasons are given for believing that a waist cord provides a necessary cognitive clue to this weight regain, and thus assists in maintaining normal weight in formerly obese people. PMID- 2187001 TI - Effect of theophylline on cortisol plasma concentrations in patients with chronic obstructive pulmonary disease. AB - To further understand the therapeutic action of theophylline, we investigated, in a randomized double-blind crossover study, the effects of a 4-day treatment with two different dosage regimens of theophylline on the circadian rhythm of cortisol plasma concentrations in seven COPD patients. Both theophylline regimens resulted in plasma concentrations in the therapeutic range (more than 7.5 mg/l). No significant differences between placebo and the active trial periods in the circadian rhythm of cortisol secretion were found. These results suggest that cortisol secretion is not influenced by therapeutic plasma concentrations of theophylline. PMID- 2187002 TI - The treatment of heroin addicts with dextromethorphan: a double-blind comparison of dextromethorphan with chlorpromazine. AB - According to the hypothesis that the development of physical dependence on and tolerance to opiates depends on the inhibition by opiates of L-asparaginase and L glutaminase activities in the brain, and the blockade by opiates of the aspartatergic/glutamatergic receptors especially NMDA, four female and fourty four male heroin addicts were included in a double-blind clinical trial. Four mg chlorpromazine (CPZ) was administered every hour and 10 mg diazepam (DIA) every 6 hours to a group consisting of two female and nineteen male inpatients. The remaining subjects received 15 mg non-opioid antitussive dextromethorphan (DM) instead of CPZ. The withdrawn addicts were controlled twice a day and yawning, lacrimation, rhinorrhoea, perspiration, goose flesh, muscle tremor, dilated pupils, anorexia, joint and muscle aches, restlessness, insomnia, emesis, diarrhea, craving and rejection of smoking as abstinence syndrome signs were observed and rated on a scale of 1, 2 and 3 points according to their intensity. All signs, except perspiration and emesis, were significantly less intense in the group given DM + DIA than CPZ + DIA. The other plus points included the immediate stop of craving and the early onset of smoking in DM + DIA group. The results are considered to be supporting evidence for the hypothesis emphasizing the blockade of NMDA receptors by opiates in opiate addiction. Furthermore, the decrease caused by non-opioid NMDA antagonists in the responsiveness of NMDA receptors appears very promising for the treatment of opiate addicts. PMID- 2187003 TI - Effect of training and detraining on in vivo insulin sensitivity. AB - Insulin sensitivity was determined in rats to clarify the effect of detraining at 1 (trained state), 2, 3, and 7 days (7 rats each) and 14 days (n = 8) after five weeks of voluntary training using euglycemic insulin clamp technique. The relationship between basal insulin and glucose shifted towards a decrease in metabolic insulin needs compared to untrained controls (n = 20). During the insulin clamp study, to maintain comparable plasma glucose and insulin levels in all groups, the glucose infusion rate had to be increased significantly (p less than 0.01) to 9.92 +/- 1.12 mg.kg-1.min-1 compared to control group (6.57 +/- 0.57). This improved sensitivity persisted for 2 days after training but was significantly lowered in the 7-days-after group (p less than 0.01). In summary, this study shows that training effect on insulin sensitivity can be determined after voluntary training in rat. This training effect lasted 2 days after training. PMID- 2187004 TI - Neuromuscular adaptations and serum hormones in females during prolonged power training. AB - Training-induced adaptations in the neuromuscular and endocrine systems were investigated in seven females during prolonged power type strength training. Great (p less than 0.05) changes occurred primarily during the earlier weeks of the 16-week training especially in the time of force production (from 161 +/- 107 to 93 +/- 65 ms to produce a 500 N force) and, correspondingly, in the average forces in the earlier positions of the (absolute) force-time curve of the leg extensor muscles. These changes were accompanied by significant (p less than 0.05) increases in the neural activation of the trained muscles in the earliest positions of the IEMG-time curve. Hypertrophic changes, as judged from muscle fibre area data of both FT and ST types, were only slight (ns.) during the entire training period. No statistically significant changes occurred during the training in mean concentrations of serum testosterone, free testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), cortisol, progesterone, estradiol (E2) or sex hormone-binding globulin (SHBG). However, the individual mean serum levels of both total and free testosterone correlated significantly (r = .81-.95, p less than 0.05-0.01) with the individual changes during the training in the time of force production and in the forces in the force-time curve of the trained muscles. The present results in female subjects indicate the important role of training-induced adaptations in the nervous system for muscular power development. In females testosterone may be of great importance for muscular power and/or strength development during prolonged training and an important indicator of the trainability of an individual. PMID- 2187007 TI - Coral and bells: the mysterious history of teethers and rattles. PMID- 2187006 TI - Effect of calcium dobesilate on the blood-retinal barrier in early diabetic retinopathy. AB - The effect of calcium dobesilate on the alteration of the blood-retinal barrier was studied in 41 adult-onset, non-insulin dependent diabetic patients with minimal or no retinopathy, randomly assigned to receive either oral calcium dobesilate (1000 mg twice daily) or a placebo for 12 months. The posterior vitreous value and the penetration ratio, determined by vitreous fluorophotometry, reflected stabilisation of blood-retinal barrier permeability in the calcium dobesilate patients and deterioration of blood retinal barrier in those given placebo. During the relatively short period of the study, one year, no significant change in microaneurysm and capillary closure gradings was observed. No side effects were associated with calcium dobesilate. PMID- 2187005 TI - Proliferative vitreoretinopathy--is it anything more than wound healing at the wrong place? AB - Proliferative vitreoretinopathy (PVR) is a reactive process of the ocular tissue after perforating trauma, retinal detachment, and surgical manipulations. Although several studies, most of them experimental, have focused on the detection of specific etiologic factors in the development of PVR, there is compelling evidence that PVR is nothing more than a physiologic tissue repair process with undesirable consequences for the retina. Important features of PVR involving the role of platelets, mononuclear phagocytes, and fibroblasts parallel the chain of events observed in tissue repair elsewhere in the body. Numerous experimental models for PVR, originally designed to find specific stimuli for the generation of intraocular traction membrane formation, have shown that the process of PVR is the common pathway of the eye's reaction to vitreoretinal trauma of any kind. Accordingly, vitreoretinal surgeons could learn a lot from the work of other disciplines, e.g. surgery and dermatology, on wound healing, and the factors known to modify wound healing elsewhere in the body should be taken into consideration. The well-established impairment of tissue repair processes caused by medical treatment with corticosteroids and cytotoxic agents suggests a combined medical approach to PVR as an adjunct to surgical treatment, using refined methods of application and dosage. Steroids and cytotoxic drugs will influence the course of PVR by suppressing macrophage recruitment and the initial inflammatory reaction as well as the proliferative phase of wound healing with traction retinal detachment, respectively. PMID- 2187008 TI - The "roots" of biomedical ethics. PMID- 2187009 TI - Event-related potentials and monoamines in autistic children on a clinical trial of fenfluramine. AB - In a double blind, crossover study of the response of autistic subjects to fenfluramine, event-related potentials (ERPs) were recorded from 7 subjects on an attention-demanding auditory choice reaction time task (ACRT). ACRT, IQ and biochemical measures were taken after 5 months placebo and 5 months fenfluramine treatment. After fenfluramine treatment blood serotonin levels fell, urinary catecholamine levels fell and the HVA/DA ratio rose. IQ and ACRT performance improved. On the ACRT subjects were asked to press a button to a rare target (500 Hz, P = 0.14) and to ignore higher pitched rare (2,000 Hz, P = 0.14) and frequent non-targets (1,000 Hz). After fenfluramine treatment N1 latencies increased. The scalp distribution of ERP maxima changes slightly with treatment. P3 maxima elicited by rare non-targets were recorded more rostrally after fenfluramine treatment. After rare non-targets N1 amplitudes at Fz decreased but P3 amplitudes at Pz increased. Early negativity after the rare non-target (particularly on the right side) was negatively correlated with the HVA/DA ratio. Subtraction of the P3 component elicited in a passive condition where no response was required from the active condition showed that P3 positivity to targets was halved with treatment. (In contrast Nd increased on fenfluramine treatment). Overall, N1 and P3 components showed greatest responsiveness to rare non-targets on fenfluramine. N1 but not P3 changes may represent slight improvement of attention-related function with treatment. Small changes in ERP latency and distribution, associated with the neuroleptic action of fenfluramine may be partly responsible for a mild improvement of IQ and ACRT performance on medication. PMID- 2187010 TI - Treatment of brain abscess. PMID- 2187011 TI - Importance of organisms producing broad-spectrum SHV-group beta-lactamases into the United Kingdom. AB - We report the isolation of three strains of Klebsiella pneumoniae sensu lato, brought into the United Kingdom by patients from Greece and Egypt, that showed plasmid-determined resistance to ceftazidime. All three produced beta-lactamases shown by DNA hybridisation studies to belong to the SHV group. One produced an enzyme that appeared to be related to, but distinguishable from, SHV-1; another SHV-2 and the third SHV-5. PMID- 2187012 TI - The effect of obstruction on the biliary excretion of cefoperazone and ceftazidime. AB - The biliary excretion of cefoperazone and ceftazidime was studied by endoscopic cannulation of the common bile duct, in patients with complete biliary obstruction and in an unobstructed control group. Patients were given each drug prophylactically for 24 h before endoscopy and as a single dose at the time of cannulation. In unobstructed patients biliary excretion of ceftazidime was passive. At the time of cannulation bile contained 10% of the peak serum concentration, rising to 20% 90 min later. Cefoperazone excretion was active. At cannulation biliary concentrations were 200% of the serum peak, 900% at 60 min and 700% at 90 min. In obstructed patients, bile sampled immediately at decompression contained neither antibiotic. Passive excretion of both drugs occurred rapidly after relief of obstruction and biliary concentrations were 20% of maximum serum levels at 60 min. Twenty-four hours later passive excretion had further improved, but the active excretion mechanism of cefoperazone had still not recovered. We conclude that obstruction impairs active as well as passive biliary excretion of antibiotics, that drainage is essential for the control of sepsis in obstructed cholangitis, and that both cefoperazone and ceftazidime achieve similar and therapeutic concentrations in bile during the 24 h after decompression. PMID- 2187013 TI - Cefodizime and cefotaxime in acute exacerbations of chronic bronchitis: a randomized double-blind prospective study in 180 patients. AB - In a double-blind prospective study, 180 patients admitted to hospital with acute purulent exacerbations of chronic bronchitis were treated for seven days with twice daily 1 g intramuscular injections of either cefodizime or cefotaxime. Sputum cultures performed before, during and immediately after treatment showed complete eradication of the infection in 89/90 given cefodizime and 86/90 receiving cefotaxime. Some symptomatic Pseudomonas aeruginosa superinfections occurred with each agent. During the follow-up week, recurrences or reinfections after apparent clearance occurred in 15 patients given cefodizime and in 21 receiving cefotaxime. Pharmacokinetic studies in blood showed mean Cmax values of 50.8 mg/l for cefodizime and 36.5 mg/l for cefotaxime, corresponding values in the sputum being 1.61 and 0.62 mg/l. Mean AUC values in both blood and sputum were 2 1/2- to 3-fold higher for cefodizime. Some features suggested better performance by cefodizime than by cefotaxime, but the clinical results were not statistically significantly different. PMID- 2187014 TI - A randomized clinical study of cefoperazone and sulbactam versus gentamicin and clindamycin in the treatment of intra-abdominal infections. AB - This report summarizes the experience of investigators in four medical centres who compared the combination of cefoperazone/sulbactam against gentamicin/clindamycin in the treatment of intra-abdominal infections. One hundred and fifty-two patients were enrolled in the study and all were evaluable for safety and tolerance, 110 were evaluable for efficacy. Of the 76 patients (49 male, 27 female) treated with cefoperazone/sulbactam 66 (86.8%) were cured, five (6.6%) improved and five (6.6%) failed to respond to treatment. Of 34 patients treated with gentamicin/clindamycin, 21 (61.8%) were cured, four (11.8%) improved and nine (26.4%) failed. Cure rates for patients receiving cefoperazone/sulbactam were significantly higher than those of patients receiving gentamicin/clindamycin (P less than 0.006). Failures in both groups were attributable in part to pseudomonal and enterococcal infection and abscess formation. The addition of sulbactam to cefoperazone rendered cefoperazone-resistant organisms susceptible to cefoperazone in 11 of the 76 cases (14.4%) and thus permitted treatment with this agent. The present study confirms the safety and clinical efficacy of cefoperazone/sulbactam and suggests that this combination is a viable alternative to an aminoglycoside plus clindamycin for intra-abdominal infections. PMID- 2187015 TI - Altered virulence of gentamicin-resistant variants of Klebsiella pneumoniae. PMID- 2187016 TI - A limiting-dilution analysis of activated circulating B cells in Crohn's disease. AB - In the present study the spontaneous in vitro production of immunoglobulins G, A, and M by peripheral mononuclear cells was evaluated, in patients with Crohn's disease, in relation to the state of B-cell activation and further characterized by limiting-dilution analysis. A total of 25 patients with Crohn's disease and 10 healthy controls was studied. The proportion of the transferrin receptor-bearing cells in the B7+ subset was higher in active Crohn's disease patients than in either those with quiescent disease or controls. There was a significant rise in the in vitro IgG, IgM, and IgA production in patients with untreated active Crohn's disease compared to either those with untreated quiescent disease or controls. When patients were followed up from the active phase to clinical remission, a significant decrease in the production of IgG and IgM was observed. IgA levels also showed a decrease, although not reaching statistical significance. When the Ig production was analyzed by limiting dilution, no difference was observed between patients and controls in terms of either precursor frequency of Ig-producing cells or patterns of frequency distribution. In both patients and controls a biphasic limiting-dilution profile was observed. This study shows that a significant B-cell activation is present in Crohn's disease patients, which is accompanied by an increase in immunoglobulin production. This study also indicates that in Crohn's disease the increased immunoglobulin production is related to an augmented B-cell clone size rather than to an increased precursor frequency. PMID- 2187018 TI - W. Grey Walter: a memoir of an extraordinary man. PMID- 2187017 TI - Intravenous immunoglobulin (IVIG) for the therapy of autoimmune disorders. AB - The weight of evidence from numerous clinical studies supports the use of IVIG, particularly at higher doses, in the treatment of a wide range of autoimmune disorders. Extensive experience has documented the safety of IVIG therapy but its present relatively high cost necessitates firmly establishing its efficacy. There is an acute need to define those disease states where IVIG is indicated and effective. Large-scale, possibly multicentered, clinical trials employing rigorous controls will resolve these questions. Concurrent fundamental immunologic studies will elucidate the mechanisms underlying the clinical effects. We are experiencing an exciting new era of effective immunotherapies and intravenous gamma-globulin preparations have already secured an important place in the therapeutic armamentarium. While one must guard against unsubstantiated applications, critical exploration of new uses for this unique product is warranted. PMID- 2187019 TI - Alpha rhythms. PMID- 2187020 TI - Beta and mu rhythms. PMID- 2187021 TI - Unusual EEG patterns. AB - Some of the unusual patterns that can be encountered on the EEG are described briefly. The patterns are grouped according to the predominant frequencies involved and/or by distinctive morphology or distribution. Those involving predominantly the alpha frequency range are alpha squeak, retained alpha, alpha delta sleep, unilateral decrease in reactivity of alpha activity, and extreme spindles. The patterns involving the beta frequency range are the fast alpha variant, posterior temporal fast activity in children, the fast spiky spindle variant, central fast activity, and diffuse paroxysmal or continuous fast activity. The patterns of predominant theta frequencies are the slow alpha variant, frontal arousal rhythm, rhythmic temporal theta activity of drowsiness, midline theta rhythms, and focal parietal theta activity. Activity in the delta range includes the transient rhythmic slowing occurring after eye closure and the more continuous posterior rhythmic slowing. Patterns with a distinct morphology or distribution include the breach rhythm, wicket spikes, zeta waves, periodic frontal sharp complexes, subclinical rhythmic electrographic discharge of adults, and the EEG pattern of holoprosencephaly. PMID- 2187022 TI - Pathogenesis and significance of abnormal nonepileptiform rhythms in the EEG. AB - In this article the present state of knowledge of physiological mechanisms underlying nonepileptiform EEG abnormalities is reviewed. Focal and widespread slow waves, background activity abnormalities, and bursts of rhythmic slow activity are discussed. Clinical and experimental data accumulated over the past four decades suggest that polymorphic slow activity is generated in cerebral cortex by layers of pyramidal cells and is probably due to partial deafferentation from subcortical areas. Unilateral background activity changes are probably due to thalamic dysfunction, and bilateral paroxysmal slow activity is due to abnormal thalamocortical circuits combined with cortical pathology. The fact that pathologic slow-wave phenomena are longer in duration than the average postsynaptic potential is also discussed. PMID- 2187023 TI - Periodic EEG patterns: classification, clinical correlation, and pathophysiology. AB - In this article, we review periodic EEG patterns, which have been classified into four different types based on their interval duration (short or long) and topographic distribution (lateralized, bilaterally independent, or diffuse and synchronous). The four patterns are: (1) periodic lateralized epileptiform discharges; (2) bilateral independent periodic lateralized epileptiform discharges; (3) periodic short-interval diffuse discharges; and (4) periodic long interval diffuse discharges. We also discuss morphology, etiologies, and clinical correlates of each pattern and possible pathophysiological mechanisms of periodicity. PMID- 2187024 TI - Altered expression of major histocompatibility complex (MHC) antigens by epidermal tumours. AB - Alteration in the major histocompatibility complex (MHC) antigen expression by cutaneous tumours may enable them to escape host defence mechanisms and to invade surrounding tissue. Immunohistochemical studies in a wide range of epidermally derived tumours demonstrated expression by keratinocytes of the class II molecule HLA-DR in squamous cell carcinoma (SCC) (2 of 8 cases) and keratoacanthoma (KA) (2 of 7 cases). Additionally, HLA-DP and DQ were expressed by single cases of SCC and KA, although, unlike the widespread distribution of DR, DP and DQ, were only present on keratinocytes adjacent to the inflammatory infiltrate. Therefore, keratinocytes in cutaneous tumours, like carcinoma cells of the colon and breast, may express class II MHC antigens during tumour growth. Beta-2-microglobulin (B2M), an invariant MHC class I marker, was absent in all cases of basal cell carcinoma. Variable loss of B2M was observed in squamous cell carcinoma, Bowen's disease and actinic keratoses, suggesting reduced B2M expression by dysplastic cells. However, the variability in B2M staining both between and within diagnostic categories restricts it's immunodiagnostic usefulness. PMID- 2187025 TI - Microcystic adnexal carcinoma: a light microscopic, immunohistochemical and ultrastructural study. AB - We report a case of microcystic adnexal carcinoma (MAC) occurring on the upper lip of an 82-year-old woman. Microscopically the tumor showed both pilar and sweat gland differentiation, involved the entire dermis and subcutaneous tissue, and invaded perineural spaces. Immunoperoxidase studies revealed carcinoembryonic antigen to be present in the ductal lining cells and in the amorphous content in the lumen, confirming sweat gland differentiation. The S-100 protein was positive in dendritic cells within the solid cell nests, but negative in cells lining cystic spaces. Ultrastructural study confirmed that the neoplasm was composed of two components, with pilar and eccrine differentiation. The former showed concentric layers of squamous epithelial cells with well-developed desmosomes and cytofilaments. The latter had ductal and alveolar structures; the ultrastructural features included: i) numerous villous folds of plasma membrane to interdigitate each other by focal desmosomes, ii) aggregates of cytofilaments, and iii) basally located myoepithelial cells which were separated from the surrounding stroma by rather thick basement membrane. In addition, distinct amyloid deposition was also observed on ultrastructural examination. To our knowledge, amyloid deposition has not been previously reported in MAC. PMID- 2187026 TI - Effect of intravenous epinephrine on serum magnesium and free intracellular red blood cell magnesium concentrations measured by nuclear magnetic resonance. AB - Hypomagnesemia is a common clinical finding in hospitalized patients and can cause hypocalcemia, cardiac arrhythmias, muscular weakness, and hypokalemia. Hypomagnesemia usually implies cellular magnesium (Mg) depletion, but stress and some clinical conditions which raise serum catecholamine concentrations may lower serum Mg (sMg) concentrations. To help investigate the mechanism and degree of the effect of catecholamines on sMg concentration, we gave intravenous epinephrine (0.1 microgram/kg/min) to 12 normal volunteers for 2 hours. The sMg concentration fell from 1.86 +/- 0.04 mg/dl to 1.63 +/- 0.05 mg/dl (mean +/- SEM, p less than 0.01). Pre-infusion intracellular free Mg (Mg++) in red blood cells (RBC) as measured by nuclear magnetic resonance spectrophotometry (NMR) was 171 +/- 7.6 microM and did not differ significantly from post-infusion RBC Mg++, 186 +/- 12.6 microM. Total blood mononuclear cell Mg content and urine Mg excretion also did not change. These data suggest that epinephrine has a small but significant effect on the lowering of sMg concentrations. Endogenous catecholamine release during stress or acute illness may therefore contribute to the hypomagnesemia seen in acutely ill patients. Our data also suggest that hypomagnesemia seen under conditions of acute stress may not always imply depleted tissue Mg stores. As no absolute change in cellular Mg or in urinary Mg excretion was demonstrated, acute intracellular shifts of Mg into blood cells and/or urinary Mg losses may not account for the hypomagnesemia. The prevalence and clinical consequences of stress hypomagnesemia require further investigation. PMID- 2187027 TI - Selenium status and cardiovascular risk factors in healthy Dutch subjects. AB - To provide further insight into the possible role of selenium in cardiovascular disease, we examined the relationship between cardiovascular risk factors, some nutritional parameters, and short- and long-term selenium status. A total of 82 healthy Dutch volunteers, 59 men and 23 women, aged 40-75 years, were studied. Means and standard deviations of selenium parameters were: plasma selenium 106.4 +/- 23.7 micrograms/L, erythrocyte selenium 0.59 +/- 0.19 microgram/g Hb, toenail selenium 0.78 +/- 0.17 ppm, and erythrocyte glutathione peroxidase activity 28.0 +/- 8.1 U/g Hb. No association was found between selenium status and gender, age, serum total-, LDL-, and HDL-cholesterol, systolic and diastolic blood pressure, alcohol intake, and body mass index. A significantly lower plasma selenium level was observed among smokers compared to nonsmokers (101.0 micrograms/L, SE = 3.9 vs 112.0 micrograms/L, SE = 3.6, p = 0.04). A significant negative association was found between erythrocyte selenium and serum levels of vitamin A and ferritin. No relevant relationship was observed between selenium status and serum fatty acid composition, vitamin E, vitamin B6, and iron. Apart from an association between smoking and short-term selenium status, we found no indications that a possible effect of selenium on cardiovascular disease may operate through the known risk factors. PMID- 2187028 TI - Malignant schwannoma of the medial plantar branch of the posterior tibial nerve. AB - Malignant schwannoma in the foot is extremely rare. The authors present a case involving the medial plantar branch of the posterior tibial nerve in a patient with neurofibromatosis, without previous history of malignant degeneration. Following full excisional biopsy, the diagnosis was made using immunohistochemical studies and electron microscopy. A review of the literature also is presented. PMID- 2187029 TI - Nonclostridial gas gangrene. AB - Although nonclostridial gas gangrene is not an unusual occurrence, relatively few cases including the distal lower extremity have been reported. Due to the serious nature of some of these infections, it is important for physicians to familiarize themselves with these nonclostridial crepitant infections, which are often confused with clostridial myonecrosis. Etiology, evaluation, and treatment is described by the authors. Also, a case study is presented. PMID- 2187030 TI - Gastroparesis: a possible complication in diabetic patients. AB - A case is presented of gastroparesis as a complication of diabetes mellitus in a 31-year-old insulin-dependent diabetic patient. The patient was admitted to the hospital for cellulitis of the right foot with ulceration of the hallux, as well as ulceration of the fifth toe of the left foot. This paper will deal with a case report and review of the literature as it pertains to gastroparesis as a complication of diabetes mellitus. PMID- 2187031 TI - A sensitive and reproducible method for the assay of human islet cell antibodies. AB - The islet cell antibody test is increasingly used to predict insulin-dependent diabetes before it is clinically apparent. Four international workshops on the test have shown wide variations in reproducibility, sensitivity and specificity. This illustrates the need for a more clearly defined method. We report a technique which offers both increased sensitivity and reproducibility. Using this method 94% of newly diagnosed diabetic children have ICA levels greater than or equal to 10 international units, whereas only 1.5% of normal children are positive at his level, and 7% of first degree relatives (aged less than 20 years) of IDDM patients. PMID- 2187032 TI - A cytofluorometric method to quantify membrane antigens on individual alveolar macrophages. AB - An immunofluorescence method for assaying membrane-bound antigens on individual alveolar macrophages (AM) collected by bronchoalveolar lavage (BAL) is described. Cells were labelled with FITC-conjugated anti-HLA-DR antibodies in a single (direct) step. Quantification of the fluorescence was performed by computer assisted cytophotometry. Alveolar macrophages, especially when obtained from cigarette smokers, exhibited an autofluorescence which interfered with the measurement of specific fluorescence. The specific fluorescence was calculated by determination of total fluorescence in the wave-length optimal for FITC and the non-specific fluorescence in a different wavelength during a second measurement. Specificity and reproducibility testing confirmed the reliability of the method. PMID- 2187033 TI - Sodium pyruvate inhibits the spontaneous release of 51Cr from RBC in chromium release assays. AB - This report describes the utility of sodium pyruvate for markedly decreasing the spontaneous release of chromium-51 from RBC in long term chromium release assays. This method can be used to increase the sensitivity and duration of cytotoxicity assays which use chromium-51-labeled RBC as targets. PMID- 2187034 TI - A simple and rapid method to determine hematopoietic growth factor activity. AB - A rapid and simple colorimetric microassay method for the determination of hematopoietic growth factor activities was established. The assay was used to detect CSF-1, GM-CSF, and IL-3 activities. The assay was based on the metabolism of the tetrazolium dye 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide to formazan by metabolically active cells. Results obtained with the colorimetric microassay are comparable with those obtained with the soft agarose assay. Advantages of the colorimetric microassay include the conservation of reagents, the shorter incubation time for the experiment, the shorter assay time, and the ability to evaluate large numbers of samples. PMID- 2187035 TI - A rapid and robust particle-enhanced turbidimetric immunoassay for serum beta 2 microglobulin. AB - A rapid particle-enhanced turbidimetric immunoassay (PETIA), for the measurement of serum beta 2-microglobulin is described. The method has a working range of 0.2 40 mg/l, with good precision and a correlation coefficient of 0.97 when compared with an established radioimmunoassay method. One of the major advantages of this assay is the stability of the calibration curve (up to at least 20 months). This, and the fact that no pretreatment of serum samples is necessary, makes the assay ideally suited for all types of routine determination. PMID- 2187036 TI - [Therapeutic evaluation of combination therapy using C-425 and antibiotics in severe bacterial infections--a double blind group comparative study. The C-425 Research Group for Infectious Comparative Study]. AB - Clinical usefulness of C-425, a native human immunoglobulin liquid preparation for intravenous injection, was studied in combination with antibiotics in severe bacterial infections in a double blind group comparison using an alkylated human immunoglobulin liquid preparation (Polyglobin, A.gamma G) as a reference drug. The following results were obtained: 1. C-425 or A.gamma G was administered to a total of 117 patients, of whom 89 patients, 45 in C-425 group and 44 in A.gamma G group, were included in the present analysis of efficacy and usefulness. Analysis of safety of the drugs included a total of 113 patients, 58 in C-425 group and 55 in A.gamma G group. 2. Efficacy and usefulness were graded according to a visual analog scale (VAS). 3. Mean efficacy values with standard deviations of VAS value were calculated at 52.0 +/- 34.9 for the C-425 group, and 47.2 +/- 34.8 for the A.gamma G group. The respective medians were 59.0 and 61.0. The Mann-Whitney U test revealed no significant differences between the two groups. When those with VAS values of 50 or above were regarded as cases of effective treatment, the efficacy rates of the two groups were also practically comparable. 4. Side effects were not observed in either drug group. 5. Mean usefulness values with standard deviations were 52.3 +/- 34.9 for the C-425 group, and 47.9 +/- 35.0 for the A.gamma G group. The respective medians were 60.0 and 61.0. The Mann-Whitney U-test revealed no significant differences between the two groups. When the cases with VAS values of 50 or above were regarded as cases of useful treatment, there were no significant differences in the utility rates between the two groups. From these results, C-425 was considered to be useful for treating severe bacterial infections when used combined with antibiotics. PMID- 2187037 TI - [A case of fatal sepsis due to Vibrio vulnificus]. AB - A 66-year-old male with chronic alcoholic liver injury was admitted on July 27, 1986 to our hospital with complaints of high fever, convulsion and skin erythema. He had consumed raw fish 3 days before, and had a scratch wound over the right arm and left leg because he had slipped in a small stream in the woods the day before admission. He was already in shock state with sepsis of V. vulnificus and DIC on admission. Although the treatment with ABPC, CP, CAZ, MINO for sepsis, and Heparin & Antithrombin III for DIC was immediately begun, he died only 10 hours after admission. On autopsy, the skin lesion revealed phlegmon with necrotizing angitis and the liver showed fatty changes with Mallory's body. The causative organism was detected from the blood and on autopsy from the skin wound, bile juice, liver, spleen, kidney and bone marrow, and its type was determined as a V. vulnificus serovar 4. It was suspected that the route of infection in this case was the raw fish rather than via the wound because the water in which he had been wounded was fresh water and the bacterium was not detected from the water, shells, nor moss existing there. PMID- 2187039 TI - The preimplantation genetic diagnosis of genetic diseases. PMID- 2187038 TI - [A case of pulmonary nocardiosis associated with middle lobe atelectasis]. AB - Pulmonary nocardiosis is a rare disease. We reported a case of pulmonary nocardiosis associated with middle lobe atelectasis. A 66-year-old female was admitted to Saga Medical School Hospital with complaints of fever, productive cough and hemosputum. Nocardia asteroides was isolated from her sputum and bronchial lavage fluid. Administration of sulfamethoxazole-trimethoprim (ST) improved her symptoms and Nocardia asteroides were rapidly eliminated from her sputum. However, she had severe side effects of ST: toxic dermatitis, granulocytopenia and liver dysfunction, whereupon administration of ST was stopped. About two weeks later, Nocardia asteroides appeared again in her sputum. Either netilmicin (NTL) or minocycline (MINO) given consecutively could not eliminate Nocardia asteroides from her sputa. Subsequently a combination therapy of OFLX administration and gentamicin inhalation was tried. This treatment improved her symptoms and eradicated Nocardia asteroides from her sputa completely. In vitro study, ST, MINO and aminoglycosides showed good susceptibility against Nocardia asteroides. In this case, it was revealed that GM inhalation therapy is also very useful for pulmonary Nocardiosis. PMID- 2187040 TI - New techniques in fertilization: intravaginal culture and microvolume straw. PMID- 2187041 TI - The sensitivity and specificity of seven lumbo-pelvic orthopedic tests and the arm-fossa test. AB - Twenty-nine lumbosacral asymptomatic and 39 symptomatic patients who attended a chiropractic clinic were examined by a practitioner who was blinded to their symptoms. Seven lumbosacral orthopedic tests, along with the arm-fossa test were scrutinized for sensitivity, specificity and diagnostic competency values. Only the arm-fossa test and heel-buttock tests had a significantly higher percentage of positive findings in symptomatic than asymptomatic cases. These same tests were the only ones which could be considered to have an acceptable diagnostic value, when both the sensitivity and specificity were taken into consideration by Youden's index. The number of positive tests was unrelated to the presence of lumbosacral symptoms. Orthopedic tests which appeared to strain several adjacent anatomical structures were most commonly positive. No particular combination of tests could predict if the patient was symptomatic or asymptomatic. Only the heel buttock test had some predictive value. It appears that these tests were of limited value in differentiating between the symptomatic and asymptomatic subjects who attended the study clinic. PMID- 2187042 TI - Neuropsychology and meaning in psychiatry. AB - The relationship between "causal" and "meaningful" (Jaspers) influences on behavior is explored. The nature of meaning essentially involves rules and the human practices in which they are imparted to a person and have a formative influence on that person's thinking. The meanings that come to be discerned in life experience are then important in influencing the shape of that person's conduct. The reasoning and motivational structures that develop on this basis are realized by the shape of the neural processing networks that constitute the mature human brain. This implies that meaning is not only realized by brain micro structure but, in part, explains its workings. This in turn entails that in psychiatry we must continue to avail ourselves both of neuropsychology/neurobiology and of dynamic/meaningful explanation. PMID- 2187043 TI - Mind-body and the future of psychiatry. AB - Philosophical perspectives are deeply relevant to psychiatric theorization, investigation, and practice. There is no better instance of this than the perennially vexing mind-body problem. This essay eschews reductionist, dualist, and identity-theory attempts to resolve this problem, and offers an ontology- "monistic dual-aspect interactionism"--for the biopsychosocial model. The profound clinical, scientific, and moral consequences of positions on the mind body relation are examined. I prescribe a radically biological cure for psychiatry's--and all medicine's--chronic dogmatism and fragmentation. PMID- 2187044 TI - The future of psychiatry. AB - Psychiatry is rapidly changing. The authors review the history of psychiatry in the United States, its gradual integration into medicine and society, and the dialectic between its "biologic" and "mentalist" outlooks. After describing the current state of the profession and its knowledge base, they discuss the likely future of the field: psychiatry's projected mode of practice and economics; its future as a science for understanding human behavior; its expected boundaries with other treatment disciplines; its anticipated relationship with academia and with the community at large; and internal issues for the profession. Unprecedented internal and external pressures on the field are likely to require important reconceptualizations of psychiatry both by its members and by the rest of the American public. PMID- 2187045 TI - The new economics of medicine: special challenges for psychiatry. AB - The ongoing economic overhaul of medicine creates two basic imperatives--boosting profits and containing costs--that pose special ethical and philosophical challenges for psychiatry. Because insurance coverage still favors inpatient care, pressures to raise revenues translate into a corresponding pressure on psychiatry as a whole to expand its diagnostic categories, and on individual psychiatrists to ascribe these diagnoses liberally and to hospitalize as many patients as possible. Reciprocally, cost containment requires all physicians to justify their care as clearly as possible and to eliminate those interventions that are not of demonstrable value. Scientific outcome studies are markedly more difficult in psychiatry than elsewhere in medicine, particularly for psychotherapeutic as opposed to pharmacologic modes of care. An emphasis on biological over psychological conceptions of mental illness and treatment might result, not because it is more likely to be correct, but because it is easier to document in conventional ways and less expensive to deliver. An economics-driven reorganization of psychiatry therefore poses serious philosophical challenges, not only for the profession and its future, but for the clinical care of patients. PMID- 2187046 TI - Peripheral metabolism of corticosteroids as a mechanism of potency modulation. PMID- 2187047 TI - Differential responses of hypothalamic LHRH-I and -II to castration and gonadal steroid or tamoxifen treatment in cockerels. AB - Changes in the hypothalamic contents of LHRH-I and LHRH-II were determined in intact and castrated cockerels injected i.m. with gonadal steroids or tamoxifen. An increase in the plasma concentration of LH after castration was accompained by a significant increase in the content of LHRH-I in the posterior hypothalamus (including the mediobasal hypothalamus and median eminence) which was reversed by oestradiol benzoate given on days 14 and 15 after castration. Under similar circumstances, testosterone propionate did not modify the hypothalamic content of LHRH-I, even though both steroids reduced the plasma concentrations of LH to levels below those of intact cockerels. Treatment of intact cockerels with oestradiol benzoate significantly increased the content of LHRH-I in the posterior hypothalamus, whilst testosterone propionate was again without effect. Tamoxifen significantly raised the plasma concentration of LH in intact cockerels and partially antagonized the suppressive effect of oestradiol benzoate and testosterone on LH secretion in castrated cockerels. However, an anti-oestrogenic effect of tamoxifen on the hypothalamic content of LHRH-I was not demonstrated. There was no evidence of any changes in the hypothalamic content of LHRH-II after castration, with or without gonadal steroid replacement. A change in the hypothalamic content of LHRH-I in response to manipulation of the steroid environment would imply an involvement of this peptide in the mechanism by which gonadal steroids regulate the release of LH. The absence of changes in the hypothalamic content of LHRH-II in the same circumstances suggest that it is not directly involved in the control of LH secretion by the gonadal steroid negative feedback loop. PMID- 2187048 TI - Gonadotrophin glycosylation and function. AB - This review emphasizes the heterogeneous structure of the gonadotrophin hormones and the influence of different oligosaccharide structures on the bioactivity of these hormones. A summary has been made of the changes in biopotency of the gonadotrophins throughout the life-cycle of the human and in different endocrine states in the rat. In general it appears that the charge of the gonadotrophin conferred by the acid radicals attached to the terminal groups on the oligosaccharide structures strongly influences biopotency. Basic structures have a greater potency in in-vitro assays, but a short half-life in the circulation, while acidic isoforms are less potent, but have a longer circulatory time and are thus more active in in-vivo estimations. More basic forms are secreted over the adult reproductive years compared with the prepubertal period and old age. The glycosyl structure of the carbohydrate groups also alters in different endocrine states and is probably also important for the bioactivity and potency of the hormone. Gonadotrophin-releasing hormone (GnRH) and gonadal steroids can influence the type of isoform synthesized and released, and therefore affect the function of gonadotrophins. GnRH enhances glycosylation, sulphation and biopotency. Oestradiol potentiates the glycosylation induced by GnRH and reduces sialylation, while testosterone increases sialylation. PMID- 2187049 TI - Effect of low temperatures on glucose-induced insulin secretion and glucose metabolism in isolated pancreatic islets of the rat. AB - The direct effect of hypothermia on the inhibition of insulin secretion may result from inhibition of the availability of energetic substrates and/or the lack of metabolic signals. In order to verify this hypothesis, the insulin secretion and the main metabolic glucose pathways were measured during the incubation of rat islets. In the presence of 16.7 mmol glucose/l and at 37 degrees C, insulin secretion was 925 +/- 119 microU/2 h per ten islets. With the same experimental conditions, glucose utilization, determined as the formation of 3H2O from [5-3H]glucose was 2225 +/- 184 pmol/2 h per ten islets, glucose oxidation measured as the formation of 14CO2 from [U-14C]glucose was 673 +/- 51 pmol/2 h per ten islets, pentose cycle determined as the formation of 14CO2 from either [1-14C]glucose or [6-14C]glucose was 37 +/- 5 pmol/2 h per ten islets; glucose oxidation by the tricarboxilic acid cycle, calculated to be the difference between glucose oxidation and pentose cycle values, was 636 pmol/2 h per ten islets. Hypothermia highly inhibited glucose-induced insulin secretion and glucose utilization. Inhibition of insulin secretion was partial at 27 degrees C since it was 2.5 times lower than that at 37 degrees C, and it was complete at 17 degrees C. Glucose oxidation in the tricarboxilic acid cycle was markedly inhibited by hypothermia since the inhibition coefficient (Q10) between 37 and 27 degrees C was 5. In contrast, glucose oxidation in the pentose phosphate shunt was enhanced at 27 degrees C, reaching 92 +/- 17 pmol/2 h per ten islets, and it was inhibited relatively little at 17 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2187050 TI - Production of anti-idiotypic antisera to rat GH antibodies capable of binding to GH receptors and increasing body weight gain in hypophysectomized rats. AB - Anti-idiotypic antibodies to rat GH antibodies were produced in both sheep and mice and shown to be capable of mimicking GH by inhibiting 125I-labelled ovine GH (oGH) binding to sheep liver membranes. The sheep anti-idiotypes were characterized further and shown to (1) inhibit 125I-labelled oGH binding to oGH antibodies, (2) inhibit 125I-labelled oGH binding to rat adipocytes and (3) be incapable of inhibiting the binding of either 125I-labelled ovine prolactin or 125I-labelled bovine insulin to sheep liver membranes. This indicated that the antibodies were not limited to certain species or tissues, but were hormone specific. Finally, these anti-idiotypic antibodies were also capable of stimulating an increase in body weight gain in hypophysectomized rats, suggesting that they may be functional as well as structural mimics of GH, although the increased body weight gain was not accompanied by any increase in circulating concentrations of insulin-like growth factor-I. PMID- 2187051 TI - Regulation by GH of insulin-like growth factor-I mRNA expression in rat epiphyseal growth plate as studied with in-situ hybridization. AB - Expression of insulin-like growth factor I (IGF-I) mRNA and its dependence on GH was studied in rat epiphyseal growth plate by in-situ hybridization. Methodological aspects of the technique were first evaluated on fixed sagittal cryosections from 28-day-old rat epiphyseal growth plates to ascertain specific hybridization. In-situ hybridization was compared on sections from 10- and 28-day old rats and the GH-dependence was studied in 35-day-old hypophysectomized rats. Expression of IGF-I mRNA was apparent in chondrocytes of the proliferative, hypertrophic and early degenerative zones of the growth plate of 28-day-old rats. The epiphyseal growth plate from 10-day-old rats showed a weak hybridization signal compared with 28-day-old rats. In contrast, the mesenchymal cells of the periosteum of 10-day-old rats showed a rather strong hybridization signal. Hypophysectomy resulted in a reduction in hybridization signal and cell number of the growth plate compared with 35-day-old age-matched normal rats. GH-Replacement therapy (200 micrograms GH s.c. every 4 h for 24 h) resulted in partially restored expression of IGF-I mRNA. The present study has shown that the IGF-I gene is expressed in the rat epiphyseal growth plate chondrocytes and that the expression is dependent on GH. The results support a paracrine/autocrine role of IGF-I for the expression of the stimulatory effect of GH on longitudinal bone growth. PMID- 2187052 TI - Hypoinsulinaemia in the lactating rat is caused by a decreased glycaemic stimulus to the pancreas. AB - An in-vitro perifusion system was devised in order to examine the secretory profiles of isolated islets of Langerhans, derived from different physiological states, when subjected to various stimuli relevant to lactation. Islets from pregnant rats secreted more insulin than did those from virgin animals; however, islets from lactating and virgin animals secreted similar amounts of insulin with all stimuli, including glucose, amino acids, cations and neurotransmitters. When virgin rats were pretreated for 5 days in vivo with GH or prolactin, insulin responses in vitro were unchanged. Cannulation of the hepatic portal vein and inferior vena cava in vivo revealed that both insulin and glucose concentrations were lower in the portal vein of the lactating rat compared with the virgin animal. It was therefore concluded that insulin concentrations are depressed during lactation as a consequence of the pancreas receiving a diminished glycaemic stimulus rather than because of any change in beta-cell sensitivity. PMID- 2187053 TI - Frontal lobe dysfunction following closed head injury. A review of the literature. AB - This review of the relationship between frontal lobe pathology and sequelae of closed head injury (CHI) emphasizes the variety of neuropsychological disturbances that may be present and factors that influence symptom presentation. First, the mechanisms of injury in CHI are briefly summarized with an emphasis on frontal involvement. This summary is followed by an overview of frontal lobe structure and function including behavioral and cognitive sequelae associated with frontal damage in other patient populations. Next, findings specifically related to frontal dysfunction in CHI patients are presented. These studies, although few in number, indicate that CHI patients frequently exhibit deficits indicative of frontal damage. The clinical implications of frontal dysfunction following CHI and potential avenues for future research are discussed. PMID- 2187054 TI - Alzheimer's beta-amyloid protein is covalently modified when dissolved in formic acid. AB - beta-Amyloid protein is a major protein component of neuritic plaques in the brain of Alzheimer's disease patients. A major advance in understanding the molecular biology of Alzheimer's disease came with the purification and sequencing of this protein. Because beta-amyloid protein is very insoluble, extreme conditions such as 88% formic acid were commonly used to dissolve its fibrils. We now report that 88% formic acid covalently modifies beta-amyloid protein fragments, probably by the formation of a formate ester to a serine in the protein. The t1/2 of the formylation is approximately 3.5 h, and the t1/2 for hydrolysis of the formylated peptide is much longer, being 9.9 h in water and 66 h in HPLC eluant. This suggests that if formic acid is used in the purification of beta-amyloid protein or peptide fragments of this protein, it is likely that some formylated peptide will be present in subsequent studies. Although unrecognized modification of a protein is inherently undesirable, it is uncertain what effects this formylation will have on ensuing studies. Certainly, investigations into the immunologic, physical, and physiologic properties of beta amyloid protein could be influenced. PMID- 2187055 TI - Astrocytes are target cells for endothelins and sarafotoxin. AB - Endothelin-1, endothelin-3, and the snake venom toxin sarafotoxin S6b stimulate the hydrolysis of phosphatidylinositol by phospholipase C with similar potencies in primary cultures of astrocytes prepared from rat brain cortex. In indo 1 loaded cells, endothelin-1, endothelin-2, endothelin-3, and sarafotoxin induce the rapid mobilization of intracellular Ca2+ stores and promote a more slowly developing influx of Ca2+. These responses were insensitive to pertussis toxin and to inhibitors of cyclooxygenase and lipoxygenase. Similar actions of endothelins and sarafotoxin were observed using astrocytes from the cerebellum and glioma cells from the C6 and NN cell lines. The endothelin receptor of astrocytes differs from the receptor previously characterized in endothelial cells from brain microvessels in that it has a high affinity for endothelin-3. Thus, brain endothelin-1 and endothelin-3 have different target cells in the brain and may have different functions. PMID- 2187057 TI - Positional and positioning vertigo and nystagmus. AB - Positional and positioning vertigo and nystagmus syndromes can be attributed to either peripheral or central vestibular dysfunction. The most common form is benign paroxysmal positioning vertigo which is caused by cupulolithiasis into the posterior semicircular canal. Other labyrinthine manifestations such as positional alcohol nystagmus, positional nystagmus with macroglobulinaemia and "heavy water" or glycerol ingestion occur because of a specific gravity differential between the cupula and the endolymph (buoyancy mechanism). Neurovascular compression of the vestibular nerve may be a causative factor for "disabling positional vertigo" which is an insufficiently described entity. Hesitation is highly justifiable since retromastoid craniectomy for microvascular decompression is the recommended management. Central positional vertigo is either induced by head movements which result in a transient ischaemia of the ponto medullary brainstem, or by a change in head position relative to the gravitational vector. The latter is comprised of at least three forms: positional downbeat nystagmus (nodulus), positional nystagmus without concurrent vertigo, and positional vertigo with nystagmus. The site of the lesion is always near the fourth ventricle and the vestibular nuclei. The most probable explanation for the positional response is a vestibular tone imbalance caused by disinhibition of the vestibular reflexes on perception, eye, head and body position. PMID- 2187056 TI - Focal-unilateral accentuation of changes observed in the early stage of Creutzfeldt-Jakob disease. AB - We report on a 67-year-old male patient with progressive right-sided hemiparesis predominating in the arm and right-sided myoclonias. The EEG showed periodic delta activity in the left hemisphere. The patient died of pulmonary embolism 10 weeks after the onset of the symptoms. The neuropathological examination was indicative of Creutzfeldt-Jakob disease: distinct spongiform changes, nerve cell loss and proliferation of astroglia in the left hemisphere were found; in the right hemisphere, however, only a few circumscribed spongiform foci were seen. There was a clear correlation between the unilateral predominance of the EEG abnormality and neuropathological changes. The hypothesized spread of infection along commissural projection pathways is supported by this pattern of lesions. PMID- 2187058 TI - Computerized tomography brain scan tumor volume determinations. Sensitivity as an objective criterion of response to therapy. AB - In an effort to define more precisely and objectively computerized tomography (CT) brain scan evidence of glioma patient response to treatment, planimetric measurements of serial CT images of enhancing tumor areas were made using a digitizing tablet interfaced to a microcomputer for computing three-dimensional tumor volumes. The ability of a single investigator to measure a "significant change" in tumor volume was determined from that investigator's coefficient of variation (COV) for triplicate volume measurements (a total of 1701) on 155 scans of 27 patients with malignant gliomas. Planimetric volume data were compared with geometric computation of volumes based upon the product of the maximum diameter of enhancing tumor and the perpendicular diameter for each image made simultaneously with each planimetric measurement. The planimetric method COV was less than that for geometric computation, and the former method was employed for analysis of response to therapy in these same patients. Overall, for a tumor volume change to be significant (COV plus 2 standard errors of the means), the percentage change was determined to be 20%. However, the smaller the tumor volume being measured, the greater was the percentage change required in order to be significant. Thus, minimal measurable changes (%) were separately defined for large (greater than 14 cc), medium (8 to 14 cc), and small (less than 8 cc) tumor volumes. Tumor volumes computed from baseline (prior to investigational therapy) and from subsequent serial CT scans were compared, with response defined as a significant change. Responses to therapy based on significant volume changes were compared in each instance to the conventional visual viewbox comparison ("Gestalt") of serial scans. In 28% of scan comparisons, planimetric technique sensitivity permitted determination of significant enlargement or reduction in tumor size, while Gestalt comparison suggested no change. The use of quantitative tumor volume analysis of planimetric determinations of changes in tumor size during investigational therapy appears to permit recognition of either progression or regression of tumor size earlier than by Gestalt comparison in one fourth of instances. PMID- 2187059 TI - Transcranial Doppler pulsatility in vasodilation and stenosis. AB - Although blood velocity in the major intracranial vessels is readily measured with transcranial Doppler ultrasound (TCD), the interpretation of velocity changes is by no means straightforward. For example, a velocity increase can arise from either a local stenosis or a decrease in downstream resistance, and these mechanisms have contradictory implications for blood flow. To determine whether TCD pulsatility might distinguish these two mechanisms, Doppler ultrasonic readings were taken from an artificial vascular model under conditions of either stenosis or distal dilation. In addition, TCD studies of nine patients with unihemispheric arteriovenous malformations (AVM's) and 16 TCD studies of seven patients with unihemispheric aneurysmal vasospasm were reviewed, and pulsatilities of the AVM's (representing decreased resistance) were compared with those of the vasospastic vessels (representing stenosis). The average percentage drop in pulsatility in the vasodilated configuration of the model/percentage increase in velocity was 0.38 +/- 0.08 (+/- standard error of the mean), while that for stenosis was 0.20 +/- 0.01. Similar comparisons of the patient population yielded 0.67 +/- 0.16 for the AVM group and 0.26 +/- 0.04 for the vasospasm group. These differences were significant (p less than 0.05). The fall in pulsatility associated with a given increase in velocity is significantly greater when the velocity increase arises from diminished downstream resistance than from stenosis. PMID- 2187060 TI - Mutism after posterior fossa surgery in children. Report of three cases. AB - Three patients aged 5 1/2 to 9 years old with mutism after posterior fossa surgery are presented. The entity is discussed with a review of 15 additional previously reported cases in children aged 2 to 11 years. In all 18 patients, a large midline tumor of the posterior fossa (medulloblastoma in nine cases, astrocytoma in five, and ependymoma in four), often attached to one or both lateral recesses of the fourth ventricle, was removed. Mutism developed 18 to 72 hours after the operation (mean 41.5 hours) in patients with no disturbance of consciousness and no deficits of the lower cranial nerves or of the organs of phonation. All of these children had spoken in the first hours after surgery. The disorder lasted from 3 to 16 weeks (mean 7.9 weeks). Speech was regained after a period of dysarthria in six of the 10 cases for whom this information was available. The various hypotheses advanced to explain the pathogenesis of this speech disorder are analyzed. PMID- 2187061 TI - Hyperthermia catheter implantation and therapy in the brain. Technical note. AB - For the treatment of malignant gliomas, a technique for implanting hyperthermia catheters was developed that utilized a stereotactic template and head stabilization frame mounted on a computerized tomography (CT) scanner. Computerized tomography scans were used to measure tumor dimensions and to determine the number, implantation depths, and active heating lengths of the catheters, which were implanted through twist-drill holes while the patient was in the CT room. Heat was subsequently delivered via implanted catheters using a computer-controlled hyperthermia system, which partially compensates for heterogeneous and time-varying tumor blood flow. PMID- 2187062 TI - Fine structure of hepatocytes during the etiology of several common pathologies. AB - Hepatocytes respond to injury by a few basic pathological reactions that are reflected in cell death, different types of degeneration, regeneration, or tumorous transformation. At the ultrastructural level, alterations of cell organelles can be observed in different combinations as a result of the injury, depending on the etiological agent(s) or pathological conditions developed. Nuclear bodies, dilation and fragmentation of rough endoplasmic reticulum (rer), swelling of mitochondria, and an increased number of lysosomes occur during acute viral hepatitis. The core and surface components of the hepatitis B virus can be localized in the liver cells in chronic hepatitis and in carriers. Close contact of hepatocytic and lymphocytic cell membranes were observed in chronic active hepatitis. Hepatocytes surrounded by an increased amount of collagen fibers are characteristic of cirrhosis. Loosely arranged, fine fibrils or condensed forms of Mallory bodies are pathognomic for alcoholic injury. A wide spectrum of alterations are noted after drug treatment: the proliferation of smooth endoplasmic reticulum (ser) as an adaptive phenomenon, focal or complete necrosis of the cell, inflammation, and the like. The fine structural analysis of hepatocytic inclusions in storage diseases has a differential diagnostic value. The storage of copper and other elements can be measured by x-ray microanalysis. The study of the hepatocytic differentiation in liver tumors is highly important in establishing the diagnosis and in proving the hepatocytic origin of the tumor. PMID- 2187063 TI - Sinusoidal endothelial cells of the liver: fine structure and function in relation to age. AB - Liver endothelial cells form a continuous lining of the liver capillaries, or sinusoids, separating parenchymal cells and fat-storing cells from sinusoidal blood. Liver sinusoidal endothelial cells differ in fine structure from endothelial cells lining larger blood vessels and from other capillary endothelia in that they lack a distinct basement membrane and also contain open pores, or fenestrae, in the thin cytoplasmic projections which constitute the sinusoidal wall. This distinctive morphology supports the protective role played by liver endothelium, the cells forming a general barrier against pathogenic agents and serving as a selective sieve for substances passing from the blood to parenchymal and fat-storing cells, and vice versa. Sinusoidal endothelial cells, furthermore, significantly participate in the metabolic and clearance functions of the liver. They have been shown to be involved in the endocytosis and metabolism of a wide range of macromolecules, including glycoproteins, lipoproteins, extracellular matrix components, and inert colloids, establishing endothelial cells as a vital link in the complex network of cellular interactions and cooperation in the liver. Fine structural studies in combination with the development of cell isolation and culture techniques from both experimental animal and human liver have greatly contributed to the elucidation of these endothelial cell functions. Morphological and biochemical investigations have both revealed little changes with age except for an accumulation of iron ferritin and a decrease in the activities of glucose-6-phosphatase, Mg-ATPase, and in glucagon-stimulated adenylcyclase. Future studies are likely to disclose more fully the role of sinusoidal endothelial cells in the regulation of liver hemodynamics, in liver metabolism and blood clearance, in the maintenance of hepatic structure, in the pathogenesis of various liver diseases, and in the aging process in the liver. PMID- 2187065 TI - Improved slides of semithin sections. PMID- 2187064 TI - Ultrastructure and function of hepatic fat-storing and pit cells. AB - The present paper reviews the literature on the ultrastructure and function of sinusoidal fat-storing cells and pit cells in the mammalian liver. Ultrastructurally, fat-storing cells are characterized by the presence of cytoplasmic fat droplets, well developed rough endoplasmic reticulum; a Golgi complex; multivesicular bodies; one or two centrioles; and few, rather small, lysosomes. These lysosomes are sometimes associated with fat droplets. Fat storing cells may bear a cilium and project characteristic cytoplasmic processes into the space of Disse. These processes contain microtubules and filaments. Fat storing cells are the main storage site of retinol esters in the mammalian body. Moreover, these cells have the potential of synthesizing several connective tissue components including the collagens type I, III, and IV; fibronectin; laminin; heparan sulfate; chondroitin sulfate; and dermatan sulfate. Pit cells are polarized cells, with most organelles localized at one site of the nucleus near the cytocentre. They are characterized electron microscopically by the presence of dense cytoplasmic granules with a specific ultrastructure, by rod cored vesicles, and by multivesicular bodies. It has recently been shown that pit cells have natural killer activity to certain tumor cells and have many features in common with large granular lymphocytes. They therefore may act in the liver as a first line of defense against neoplasia, metastasis, and viral infections. PMID- 2187066 TI - Improved sectionability of paraffin-embedded specimens that initially are fixed in EM fixatives. PMID- 2187067 TI - Cholinergic synapses in the central nervous system: studies of the immunocytochemical localization of choline acetyltransferase. AB - Cholinergic synapses can be identified in immunocytochemical preparations by the use of monoclonal antibodies and specific antisera to choline acetyltransferase (ChAT), the synthesizing enzyme for acetylcholine (ACh) and a specific marker for cholinergic neurons. Electron microscopic studies demonstrate that the fibers and varicosities observed in light microscopic preparations of many brain regions are small-diameter unmyelinated axons and vesicle-containing boutons. The labeled boutons generally contain clear vesicles and one or more mitochondrial profiles. Many of these boutons form synaptic contacts, and the synapses are frequently of the symmetric type, displaying thin postsynaptic densities and relatively short contact zones. However, ChAT-labeled synapses with asymmetric junctions are also observed, and their frequency varies among different brain regions. Unlabeled dendritic shafts are the most common postsynaptic elements in virtually all regions examined although other neuronal elements, including dendritic spines and neuronal somata, also receive some cholinergic innervation. ChAT-labeled boutons form synaptic contacts with several different types of unlabeled neurons within the same brain region. Such findings are consistent with a generally diffuse pattern of cholinergic innervation in many parts of the central nervous system. Despite many similarities in the characteristics of ChAT-labeled synapses, there appears to be some heterogeneity in the cholinergic innervation within as well as among brain regions. Differences are observed in the sizes of ChAT-immunoreactive boutons, the types of synaptic contacts, and the predominant postsynaptic elements. Thus, the cholinergic system presents interesting challenges for future studies of the morphological organization and related function of cholinergic synapses. PMID- 2187068 TI - Monoamine synaptic structure and localization in the central nervous system. AB - The monoamines dopamine, noradrenaline, adrenaline, and serotonin as well as the diamine histamine have a widespread distribution in the central nervous system within synaptic terminals and nonsynaptic varicosities. In certain regions of the central nervous system the monoamines are contained in varicosities that have no synaptic specialization associated with them, suggesting a possible neuromodulatory role for some of the monoamines. The majority of monoamine labelled structures are synaptic terminals which are characterized by the presence of small, clear vesicles (40-60 nm) and large, granular vesicles (70-120 nm) within the terminal. A third population of vesicles--small, granular vesicles -which are visible only after histochemical staining, are probably the equivalent of the small, clear vesicles present after either autoradiographic or immunohistochemical labelling. Most monoamine containing terminals contact dendrites and dendritic spines and, less frequently, neuronal somata and other axons. Both asymmetrical and symmetrical membrane specializations are associated with monoaminergic terminals; however, asymmetrical contacts are the most frequent type found. These ultrastructural results indicate that monoamine containing terminals and varicosities in general share many common morphological features, but still have diverse functions. PMID- 2187069 TI - GABAergic synapses in the brain identified with antisera to GABA and its synthesizing enzyme, glutamate decarboxylase. AB - GABA is a known inhibitory neurotransmitter in the mammalian brain. The site of GABAergic synapses can be determined with immunocytochemical methods that localize either GABA or its synthesizing enzyme, glutamate decarboxylase (GAD). In general, GABAergic axon terminals contain pleomorphic synaptic vesicles and form symmetric synapses. However, a small number of GABAergic axon terminals in selected brain regions (spinal cord, cerebellum, superior colliculus, striatum, globus pallidus, inferior olive, and substantia nigra) form asymmetric synapses. GAD- and GABA-immunoreactive processes that contain synaptic vesicles participate in every known morphological type of chemical synapse. These include axosomatic, axodendritic, axospinous, initial segment, axoaxonic, dendrodendritic, serial, reciprocal, and ribbon synapses. Although GABAergic synapses form a heterogeneous group, they most commonly form axosomatic, axodendritic, and initial segment synapses in the brain and spinal cord. These findings provide helpful guidelines for the identification of GABAergic synapses in future studies. PMID- 2187070 TI - Automation and computerization of chromogenic LAL assay method for bacterial endotoxin using 96-well microtiter plate. AB - A high degree of automation was achieved for a chromogenic substrate Limulus amebocyte lysate (LAL) assay method for bacterial endotoxin using a Cetus Pro/Group Liquid Handler and 96-well microtiter plates. A Titertek Multiskan Reader was interfaced with an IBM PC using a LOTUS MEASURE software to capture optical density values of samples in a LOTUS 1-2-3 spreadsheet. A password protected, menu-driven macro programmed in LOTUS 1-2-3 automates the calculation, evaluation of assay parameters, documentation, and generation of a formatted three-page report suitable as a primary record. All assay operations, including testing 19 samples against a four-point standard curve in replicates of four each, the calculation of results, and generation of a report, are completed in less than 40 minutes. The relative standard deviation (RSD) of the assay is approximately 7%, which compares favorably with the robot automated system. PMID- 2187071 TI - The effect of zidovudine on platelet count in HIV-infected individuals. AB - Seventy-four HIV-infected homosexual males belonging to CDC groups IIB, III, and IVC2 were treated with increasing doses of zidovudine within the Multicentre Canadian AZT Trial. Following a 3 week observation period, consenting volunteers received 600 mg/day for 18 weeks, 900 mg/day for 9 weeks, and 1,200 mg/day for 9 weeks. This was followed by a 6 week washout period after which zidovudine was restarted at 1,200 mg/day for 18 weeks. Patients were followed for a total of 63 weeks. Every 3 weeks they underwent a full clinical and laboratory assessment. For the purpose of this analysis, subjects were divided according to the mean initial platelet value (greater than or equal to 150,000 or less than 150,000/L) into normals (n = 57) and thrombocytopenics (n = 12), respectively. Analysis of variance was used to compare the mean platelet values at each zidovudine dose. All comparisons were made against baseline values. Zidovudine increased platelet counts in normal and thrombocytopenic subjects. The magnitude of this effect varied depending on the baseline platelet count. Among normals, the platelet count increased from 241,000 +/- 45,000/L at baseline to 261,000 +/- 51,000/L (p less than 0.01). while receiving 600 mg/day of zidovudine. This effect was self limited, reaching a peak by week 3. The platelet count decreased to baseline values despite increasing the dose of zidovudine to 900 or 1,200 mg/day. The platelet count further decreased to 218,000 +/- 43,000/L during the washout phase (washout vs. 1,200 mg, p less than 0.01).2+ not found to be dose related. The platelet count decreased to 101,000 +/- 34,000/L during the washout phase (washout vs. 1,200 mg/day, p less than 0.07).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2187072 TI - Analysis of the secondary structure of the human immunodeficiency virus (HIV) proteins p17, gp120, and gp41 by computer modeling based on neural network methods. AB - A neural network computer program, trained to predict secondary structure of proteins by exposing it to matching sets of primary and secondary structures from a database, was used to analyze the human immunodeficiency virus (HIV) proteins p17, gp120, and gp41 from their amino acid sequences. The results are compared to those obtained by the Chou-Fasman analysis. Two alpha-helical sequences corresponding to the putative fusigenic domain and to the transmembrane domain of gp41 could be predicted, as well as a possible binding site between p17 and gp41. On the basis of the secondary structure predictions, a three-dimensional model of p17 was constructed. This model was found to represent a stable conformation by an analysis using an energy-minimization program. The model predicts that p17 is attached to the membrane only by the acylated N-terminus, in analogy with the N terminus of the gag protein of other retroviruses and also with the src oncogene protein p60src. The intracellular C-terminal part of gp41 may act as a receptor by electrostatic interaction with p17. PMID- 2187073 TI - Amplification of pBR322 plasmid DNA in Escherichia coli relA strains during batch and fed-batch fermentation. AB - Fermenter studies under batch and fed-batch conditions were carried out to test the possibility of plasmid pBR322 production in large amounts by using E. coli relA strains. High amplification rates of pBR322 plasmid DNA were observed in E. coli CP79 (relA) and E. coli CP143 (relA) in both batch and fed-batch cultivation after exhaustion of the amino acid arginine. The concentrations of plasmid DNA per unit of biomass were nearly the same in batch and in fed-batch fermentations of E. coli CP79 and E. coli CP143. Therefore, the significantly higher biomass concentration of the two strains after fed-batch fermentation gave a dramatic increase in the yield of plasmid DNA per litre of medium in comparison to the batch process. The results support the suggestion that E. coli relA strains are suitable hosts for production of large amounts of ColE1-derived plasmids for recombinant DNA research. PMID- 2187074 TI - Electroporation and expression of plasmid pBR322 in Klebsiella aerogenes NCTC 418 and plasmid pRK2501 in Pseudomonas putida CYM 318. AB - Klebsiella aerogenes NCTC 418 and Pseudomonas putida CYM 318 were transformed via high-voltage electroporation with plasmids pBR322 and pRK2501, respectively. The number of transformants obtained was dependent on the applied voltage, capacitance, and cell recovery procedure. For example, 7.87 x 10(4) transformants/micrograms DNA were obtained at 2500 V, 25 muF when K. aerogenes cells were electroporated with pBR322 DNA. A lower voltage (1500) and capacitance (3 muF) yielded 2.4 x 10(3) transformants/micrograms DNA. P. putida CYM 318 required a 24 h outgrowth period to assist in the recovery of transformants containing pRK2501. Electroporation may be a useful protocol to transform bacterial strains that are not easily transformed by traditional methods. PMID- 2187075 TI - Development and application of a radioimmunoassay for fluphenazine based on monoclonal antibodies and its comparison with alternate assay methods. AB - The development of a monoclonal antibody towards fluphenazine allows the measurement of plasma concentrations of this highly potent neuroleptic. The method demonstrates sufficient sensitivity to measure 0.02 ng of fluphenazine per milliliter of plasma and employs a 150-microL plasma extract derived from a 2-mL plasma sample. The procedure is linear over the concentration range of 0.02 to 2.5 ng/mL, with a mean overall coefficient of variation of less than 3%. The validity of the described monoclonal-based RIA procedure was confirmed by comparison to alternate assay methods in replicate samples. Comparison to a newly developed HPLC-coulometric procedure in 159 samples showed a strong correlation, with a slope value of close to unity (1.0484) and a coefficient of correlation of 0.8136, while comparison to a previously developed polyclonal-based RIA procedure showed a correlation of 0.95 and a slope of 0.91 (n = 26). PMID- 2187076 TI - Regional changes in sympathetic nerve activity and baroreceptor reflex function and arterial plasma levels of catecholamines, renin and vasopressin during naloxone-precipitated morphine withdrawal in rats. AB - The aim of the study was to examine regional changes in sympathetic nerve activity (SNA) and baroreceptor function and arterial plasma catecholamines, arginine vasopressin (AVP) and plasma renin activity during morphine withdrawal in chloralose-anesthetized rats. Dependence was induced by s.c. morphine base pellets. Adrenal, renal and splanchnic SNA and SNA from the lumbar sympathetic chain were recorded before and after i.v. injections of naloxone. Baroreceptor function was examined with phenylephrine-induced increases in mean arterial pressure. In separate experiments, arterial plasma norepinephrine, epinephrine, dopamine, plasma renin activity and AVP were measured before and after naloxone precipitated withdrawal. Naloxone administration elicited an increase in mean arterial pressure and heart rate. Although renal SNA was inhibited by approximately 50%, adrenal SNA and lumbar SNA increased by approximately 400 and 80%, respectively. Splanchnic SNA did not change significantly. The baroreceptor mediated inhibition of adrenal SNA was facilitated while that for renal SNA was attenuated. The arterial plasma level of norepinephrine was doubled and epinephrine increased almost 20-fold. AVP increased about 15-fold, whereas plasma renin activity showed only a minor increase after naloxone. This study shows that a marked differentiation of the SNA response occurs during morphine withdrawal in rats, which suggests an interaction between opioid receptors and the control of regional sympathetic output. Furthermore, large amounts of AVP and epinephrine are released, which probably contribute to the cardiovascular changes seen in the withdrawal phase. PMID- 2187077 TI - Combination nasal support breathing flange with hollow obturator prosthesis. A clinical report. PMID- 2187078 TI - Three-dimensional photoelastic stress analysis of the ferrule effect in cast post and cores. AB - The effect of a metal collar on stress distribution with cast post and cores was studied by using three-dimensional photoelastic models of maxillary canine teeth of average dimensions. Standardized parallel post and cores were cemented into the models, with half of the samples incorporating a 1.5 mm metal collar. A 400 gm load was applied to the cingulum of the cores and stresses were frozen in the models. The posts were removed, the teeth were sectioned, and stresses were measured with a circular polariscope. In both groups the greatest stress concentration was found at the lingual apex of the post. On a point by point basis, stresses were higher in the collared specimens. Variation in stress magnitude among five preselected points was greater within the noncollared group. PMID- 2187079 TI - Correlation between air-drying duration and bond strength of composite resins to teeth. AB - Cavity preparations involve both enamel and dentinal walls, but moisture contamination of these surfaces adversely influences the effectiveness of bonding interface. This in vitro study investigated the relationship between air-drying time and the bond strength to bovine enamel and dentin for two types of composite resins and their bonding agents. Comprehensive shear bond tests were performed with a universal testing machine, and mean bond strengths were computed by an analysis of variance and by Scheffe's multiple comparison test. No statistical differences were noted between the bond strength to the unetched and etched enamel and air-drying duration for bondings. The bond strengths to the etched dentin was comparable despite the time of air drying, but the bond strengths to unetched dentin were dependent upon the length of air drying. PMID- 2187080 TI - Ferrule design and fracture resistance of endodontically treated teeth. AB - This study evaluated the fracture resistance of pulpless teeth with various ferrule designs and amounts of coronal tooth structure. One millimeter of coronal tooth structure above the crown margin substantially increased the fracture resistance of endodontically treated teeth, whereas a contrabevel at either the tooth-core junction or the crown margin was ineffective. The thickness of axial tooth structure at the crown margin did not appreciably improve resistance to fracture. PMID- 2187081 TI - A provisional and new crown to fit into a clasp of an existing removable partial denture. AB - A technique that forms an abutment crown to fit into an existing clasp of a removable partial denture by relining an acrylic resin pattern is described. The outer contour of the pattern is made within an irreversible hydrocolloid impression by use of Duralay autopolymerizing acrylic resin applied with precision dispensers. The pattern is formed before tooth preparation and is made approximately 0.4 mm thick. After tooth preparation, the shell pattern is relined with the same autopolymerizing resin and the existing removable partial denture is fitted over it. The gross pattern is trimmed and the margins refined on a die made from an elastomer impression. The refined pattern is cast and finished, avoiding reduction of the contours established. A second crown is similarly formed in tooth-colored autopolymerizing acrylic resin. It serves as a provisional restoration that allows the patient to wear the removable partial denture while the laboratory procedures are performed. PMID- 2187082 TI - The influence of psychologic factors on patient satisfaction with complete dentures. AB - This study investigated the relationship between satisfaction with complete dentures and some psychologic factors. New dentures were made for 130 patients who were investigated during their treatment. A neuroticism scale and the Health Locus of Control scale were used to investigate the patient's personality. The patient-dentist relationship was evaluated by asking patients their opinions about the treatment, and patient attitude toward dentures in general and their expectation toward the new dentures were evaluated by means of a questionnaire. No relationship was found between dissatisfaction and patient personality. A low relationship was found between dissatisfaction and the patient's opinion about the treatment, and a moderate relationship was found between dissatisfaction and the patient's attitude toward dentures. A patient's attitude toward dentures, measured by the questionnaire before new dentures were received, is a prospective tool for patient satisfaction with new dentures. PMID- 2187083 TI - Prosthodontic considerations for the transmandibular implant. AB - The transmandibular implant has been designed to provide the patient with a severely atrophic mandible an implant that will bear the masticatory load. Thirteen edentulous patients treated with maxillary complete dentures and mandibular overdentures retained by the transmandibular implant were examined biannually for 2 years. Prosthodontic complications included the development of parafunctional habits, "combination syndrome," and epulis in association with the mandibular denture. Surgery was necessary to control chronic mucosal irritation related to muscle pull in one patient. Among the soft tissue parameters, plaque index, gingival index, and sulcus depth demonstrated statistically significant correlations (Spearman). All patients reported an absence of discomfort and those with previous functional complaints reported the ability to masticate all foods. Patient response to overdenture reconstruction with the transmandibular implant seems to be similar to that observed with the combination case. Oral hygiene appears to be directly related to the soft tissue response. PMID- 2187084 TI - A clinical study of joint sounds in subjects with restored occlusions. AB - It has been implied that temporomandibular joint sounds must be treated to eliminate the sounds before restorative treatments are attempted. This study explored the possibility that joint sounds do not present a problem when other symptoms are absent. A group of 35 subjects with restored occlusions were studied for the presence of temporomandibular joint dysfunction symptoms using clinical examination, questionnaires, and the pantographic reproducibility index. Forty six percent had some degree of temporomandibular joint dysfunction. Seventeen of 18 subjects (94%) with joint sounds were free of other symptoms. Therefore, the use of joint sounds as a symptom of temporomandibular joint dysfunction is questionable when not accompanied by other clinical symptoms. Subjects who had temporomandibular joint dysfunction symptoms were treated with occlusal splint therapy and occlusal adjustments. The period of time to eliminate the symptoms was 2 to 16 weeks with an average of 7 weeks. This study concludes that the presence of only joint sounds does not seem to be a hindrance to restorative treatments. PMID- 2187085 TI - An impression tray hanger for disinfection. AB - This article describes in detail a method for making a holder for impression trays. The procedure uses a pattern that can easily be made in the office. A mold is made from the pattern and parts are processed in acrylic resin. Many parts can be made from the same mold and several holders can be made before it is necessary to remake the mold. PMID- 2187086 TI - Comparison of weight reduction in different designs of solid and hollow obturator prostheses. PMID- 2187087 TI - A provisional restorative technique for laminate veneer preparations. PMID- 2187088 TI - Autologous immune complex glomerulonephritis induces abnormal embryonic development. AB - Young female random-bred Wistar rats were immunized with homologous renal brush border membranes. The immunized animals exhibited all the clinical and immunopathological characteristics of chronic autologous immune complex glomerulonephritis (Heymann nephritis) closely resembling the idiopathic membranous glomerulonephritis in humans. The animals were subsequently mated. Congenital malformations and fetal growth retardation were observed in the offspring of the nephritic mothers; high incidence of embryonic/fetal resorptions was also observed. The types of anomalies were microphthalmia, cataractic lens, abnormal retina, micrognathia, cleft palate, lordosis, fetal edema, variable hemorrhage, omphalocele, syndactaly and cryptochidism. The most frequently observed anomaly was associated with the eye. Immunofluorescent studies indicated that no rat IgG was detected in the extraembryonic membranes, embryo or fetuses. Rat complement C3 was also absent around the conceptuses. The pathophysiologic mechanism leading to such deleterious embryonic/fetal effect is not clear. PMID- 2187089 TI - Renovascular hypertension in China--report of 200 cases. AB - Renal arteritis and fibromuscular dysplasia are two common causes of renovascular hypertension in China. The diagnostic approach now is arteriography or digital subtraction arteriography first, followed by renal vein renin assays to evaluate the functional significance. Surgical treatment is preferred if clinical status of the patients permits. PMID- 2187090 TI - The value of the captopril test and the effect of captopril on renal function. AB - We have investigated the use of captopril as a screening test for renovascular hypertension and compared the effects of captopril on renal function in patients with renovascular hypertension and those without renovascular hypertension. The captopril test and kidney gamma scintigraphy were carried out in 50 hypertensive patients, 13 with renovascular hypertension and 37 without. Blood samples were drawn for the determination of plasma renin activity and kidney gamma scintigraphy was done before and 60 minutes after 50 mg oral captopril administration. Results suggesting the diagnosis of renovascular hypertension are the following: a basal and stimulated plasma renin activity of 4 ng ml/hr or more and an absolute increase in plasma renin activity of 3 ng/ml/hr or more if basal plasma renin activity was less than 4 ng/ml/hr. Data from kidney gamma scintigraphy showed that captopril causes a decrease in clearance rate at 20 minutes in patients with renovascular hypertension but not in patients without renovascular hypertension. We conclude that the captopril test can be used to screen for renovascular hypertension, but catopril may impair the renovascular hypertensive patient's renal function. PMID- 2187091 TI - The effect of intravenous captopril on right and left ventricular load and function in moderate-severe essential hypertension. AB - The acute haemodynamic effects of intravenous captopril were measured, and left ventricular function was analysed by radionuclide angiography in eleven patients with moderate to severe hypertension. All subjects received 1 mg captopril by bolus injection initially, followed at 10 minute intervals by 2 mg or 5 mg injections according to blood pressure response. Eight patients experienced an acute reduction of blood pressure whilst three patients remained unresponsive. The onset of action was within 5 minutes with a peak effect at 5 to 10 minutes and duration of action lasting 20 to 30 minutes. The haemodynamic effects were characterised by arteriolar dilatation (reduced systemic vascular resistance P less than 0.01), and apparent venous dilatation (reduced right atrial, pulmonary wedge pressure, P less than 0.05 and 0.01 respectively). Pulmonary vascular resistance was not altered, ejection fraction remained unchanged and isovolumic relaxation period was lengthened (119 +/- 20.1 to 147.39 +/- 21.15, P less than 0.05). Coronary perfusion pressure gradients dropped (123.8 +/- 5.6 to 107.1 +/- 11.3 mmHg, P less than 0.001) following intravenously administered captopril. Intravenous captopril is effective in reducing arterial pressure rapidly with minimal adverse effects. This suggests that it may be useful as an alternative regimen for severe hypertension. The prolongation of the isovolumic relaxation period accounted for the decrease of coronary filling load. PMID- 2187092 TI - Mechanism for low renin in blacks: studies in hypophysectomised rat model. AB - Black people have a lower plasma renin activity (PRA) than is appropriate for the level of blood pressure, but the mechanism remains unknown. Studies in our laboratory, using the hypophysectomised (Hypox) rat model, have provided a partial explanation of the inappropriately low PRA with respect to BP. Kidneys were isolated and perfused and renin secretion responsiveness studied with isoproterenol (Iso) infusion, calcium (Ca) depletion, and pressure reduction; an enriched preparation of juxtaglomerular (JG) cells was prepared for determination of cellular renin content (CRC); and preparations of isolated renin granules (IRG) and plasma membrane vesicles (PMV) from the purified JG cells were used to assess the storage and compartmentalisation of renin. Renin secretion was lower in Hypox than in normal and sodium (Na) deprived rats. On the other hand, CRC, IRG, and PMV were identical (statistically) in Hypox and Na deprived rats. Despite identical content and storage, kidneys from Hypox rats secreted significantly less renin in response to Iso, Ca depletion, and low pressure. One interesting observation is that upon stimulation, PMV of Hypox rats stored a much larger percentage of renin than normal or Na deprived rats, suggesting that the PMV may play a role as a renin sink in the low PRA levels observed in the Hypox rats. Since black people have renin profiles and responsiveness similar to those in Hypox rats, this model may be useful in studying the mechanisms responsible for their lower PRA. PMID- 2187093 TI - Effectiveness and safety of captopril in Sudanese hypertensive patients. AB - This study reports on the effectiveness, safety and acceptability of captopril in 36 Sudanese patients, who were classified as resistant, moderate to severe and mild according to initial diastolic blood pressure and history of treatment. The patients were titrated against a six-step captopril treatment regime with or without hydrochlorothiazide and reserpine. The median follow up period was 11.6 month. The initial median pre-treatment blood pressure was 159/101, 182/120 and 217/130 and at the end of study 125/77, 120/74 and 165/95 for the mild, severe and resistant groups respectively. Tolerance was good and side effects were mild and similar to others reported in literature. The effective daily treatment was 25-50 mg captopril for mild hypertension, 50 to 100 mg captopril with 50 mg hydrochlorothiazide for severe hypertension while it was 225 mg captopril with 50 to 100 mg hydrochlorothiazide and a need for a third drug in 30% of patients in the resistant group. These results reveal normal responsiveness to captopril among black Sudanese patients with good tolerance and safety. PMID- 2187094 TI - The pathogenesis of hypertension: an overview. PMID- 2187095 TI - Interventional ultrasound in pregnant macaques: embryonic/fetal applications. AB - Similarities in developmental biology between human and nonhuman primates have resulted in the use of macaque species as models in perinatal research. Studies have frequently included invasive surgical procedures or may have required "blind" injections. Several techniques have been established in human subjects using ultrasound as a guide such as cordocentesis and fetal therapy. These techniques have been applied to the nonhuman primate laboratory setting, which significantly decreases the risk of pregnancy loss due to experimental intervention. PMID- 2187096 TI - Nonhuman primates and teratological research. AB - Nonhuman primates were first recognized as models for the study of developmental toxicity (teratology) following the thalidomide tragedy. Since that time they have played important roles in both testing of drugs for human safety and as models for studying specific malformations commonly seen in children. Although in vitro and alternative test systems using lower animal forms or simplified test systems have been incorporated into developmental toxicity studies, whole animal testing will be required for the foreseeable future because of the complex relationship of the maternal/embryofetal/placental unit. The nonhuman primate will be particularly valuable where equivocal results are experienced in other commonly used laboratory species, when the drug/chemical is likely to be used during pregnancy, and for human-derived biotechnical products which often are not bioactive in nonprimate species. PMID- 2187097 TI - Antitermination of characterized transcriptional terminators by the Escherichia coli rrnG leader region. AB - We have used a plasmid antitermination test system to examine the response of an Escherichia coli rRNA operon antiterminator to transcription through Rho dependent and Rho-independent terminator-containing fragments. We also monitored transcription through multiple copies of a terminator to explore the mechanism of rrn antitermination. Four principal observations were made about antitermination and transcriptional terminators. (1) The rrn antiterminator mediated efficient transcription through Rho-dependent terminators. (2) Under the influence of the rrn antiterminator, RNA polymerase transcribed through two and three copies of the Rho-dependent 16 S----terminator with nearly the same efficiency as through one. (3) The antiterminator had less effect on fragments containing Rho independent terminators; the rpoC t fragment and three fragments derived from the rrnB terminator region stopped antiterminated transcription. Four other Rho independent terminator fragments were weakly antiterminated in our test system. (4) Surprisingly, the strength of these terminator fragments was not strongly related to properties such as the -delta G or number of trailing uridine residues of their canonical Rho-independent structures, but appears to be related to additional downstream terminators. We have drawn the following conclusions from these experiments. First, that ribosomal antitermination primarily reverses Rho dependent termination by modifying the RNA polymerase elongation complex. Transcription through a 1700 nucleotide, multiple terminator sequence showed that the antiterminator caused persistent changes in the transcription process. Second, that fragments derived from the Rho-independent rrnB and rpoBC terminator regions can effectively stop antiterminated transcription. Third, that efficient in vivo termination may often involve regions with complex multiple terminators. PMID- 2187098 TI - Refined crystal structure of type III chloramphenicol acetyltransferase at 1.75 A resolution. AB - High level bacterial resistance to chloramphenicol is generally due to O acetylation of the antibiotic in a reaction catalysed by chloramphenicol acetyltransferase (CAT, EC 2.3.1.28) in which acetyl-coenzyme A is the acyl donor. The crystal structure of the type III enzyme from Escherichia coli with chloramphenicol bound has been determined and refined at 1.75 A resolution, using a restrained parameter reciprocal space least squares procedure. The refined model, which includes chloramphenicol, 204 solvent molecules and two cobalt ions has a crystallographic R-factor of 18.3% for 27,300 reflections between 6 and 1.75 A resolution. The root-mean-square deviation in bond lengths from ideal values is 0.02 A. The cobalt ions play a crucial role in stabilizing the packing of the molecule in the crystal lattice. CAT is a trimer of identical subunits (monomer Mr 25,000) and the trimeric structure is stabilized by a number of hydrogen bonds, some of which result in the extension of a beta-sheet across the subunit interface. Chloramphenicol binds in a deep pocket located at the boundary between adjacent subunits of the trimer, such that the majority of residues forming the binding pocket belong to one subunit while the catalytically essential histidine belongs to the adjacent subunit. His195 is appropriately positioned to act as a general base catalyst in the reaction, and the required tautomeric stabilization is provided by an unusual interaction with a main-chain carbonyl oxygen. PMID- 2187099 TI - Promoters and autogenous control of the Escherichia coli hupA and hupB genes. AB - Three start sites and a single start site for transcription of the hupB and hupA genes, respectively, have been identified in Escherichia coli. Preceding the RNA start sites are DNA sequences that conform to canonical promoter consensus sequences. The two most upstream promoters of the hupB gene function in vivo at comparable efficiency, while the third is not expressed significantly. Both hupB and hupA genes possess a DNA sequence with a rho-independent transcriptional terminator in their respective regions downstream from the coding regions. The hup genes are both transcribed in vivo into monocistronic mRNA molecules. Upon introduction of an HU-overproducing plasmid carrying either the hupB or the hupA gene into the wild-type and hup single deletion mutants, the intracellular levels of mRNA from the chromosomal hup genes are reduced. The HU-1 and HU-2 proteins both repress both hup genes, repression of the hupB gene being less efficient. The HU protein selectively represses mRNA synthesis starting at the hup promoters in the hupB promoter-CmR and hupA promoter-KmR fusion genes, but does not have a negative regulatory effect on mRNA synthesis from the true CmR and KmR promoters. These findings suggest that the signals for the actions of HU proteins are located in the DNA regions upstream from the sites near the 5' extremities of the coding regions of the hupB and hupA genes. PMID- 2187100 TI - Morphology of the dorsal vessel in the abdomen of the blood-feeding insect Rhodnius prolixus. AB - The dorsal vessel (DV) in the abdomen of the blood-feeding insect Rhodnius prolixus was divided functionally into two regions, the heart, into which haemolymph entered the DV through four pairs of ostia located in abdominal segment VII, and the aorta, along which the haemolymph was propelled from abdominal segment VI to the thorax. Osmium-fixed whole mounts revealed the DV to consist of spirally arranged striated muscle fibers and to possess two rows of ventrally attached longitudinal fibers extending the length of the abdomen. Seven pairs of alary muscles were found attached to the DV in the posterior abdominal segments. Contractions of the alary muscles attached to the ventral surface of abdominal segments VII and VIII served to expand the heart. Electron microscopy revealed the DV to consist of a thin layer of contractile elements surrounded by an inner (intima) and outer (adventitia) connective tissue layer. Embedded in the intima along each lateral side of the DV were two large groups of endocardial cells extending the length of the DV. A small group of pericardial cells was embedded in the adventitia along the mid-ventral side of the DV, and clusters of pericardial cells were found attached to the alary muscles. Nerve terminals were found only on the heart: they contained agranular synaptic vesicles approximately 30 nm in diameter and densely stained granules approximately 100-120 nm in diameter. These structural components are discussed in relation to the role of the DV in circulation. PMID- 2187101 TI - Detection of rabies virus antibodies in fruit bats (Eidolon helvum) from Nigeria. AB - Fruit bats (Eidolon helvum) were collected from three different localities in Western Nigeria: Oti, Ibadan and Idanre. Fifty serum samples were analyzed using a modified rapid fluorescent focus inhibition technique against rabies, Mokola, Lagos bat and Duvenhage viruses. Twenty-five brain samples were screened for rabies and related lyssavirus antigens by direct fluorescent antibody microscopy and by an indirect fluorescent antibody technique with rabies anti-nucleocapsid monoclonal antibodies. All brain samples were negative. Two serum samples had relatively high anti-rabies activity; no neutralizing activity was detected against Mokola, Lagos bat or Duvenhage viruses. PMID- 2187102 TI - Biochemical assay of Alzheimer's disease--associated protein(s) in human brain tissue. A clinical study. AB - The concentration of Alzheimer's disease-associated protein (ADAP) was measured in postmortem brain tissue samples of temporal or frontal cortex from 111 human brains using a sandwich immunoassay. Alzheimer's disease-associated protein has three major ALZ-50-reactive subunits, including A-68. This assay utilizes ALZ-50 and a rabbit antibody raised against a highly ADAP-enriched brain protein fraction. The frequently observed cross-reactivity of ALZ-50 with normal brain components in direct immunoassays is minimized by this configuration. There were 27 normal controls, 28 neurologic disease controls, and 56 Alzheimer's disease cases. The normal control and neurologic disease control cases had essentially no detectable level of ADAP, while ADAP was clearly detected in 85.7% of the Alzheimer's disease cases. Clinical dementia, neuritic plaques, and old age per se are not correlated with increased ADAP levels. This biochemical assay of ADAP may prove to be helpful as an adjunct in the clinicopathologic diagnosis of Alzheimer's disease. PMID- 2187103 TI - [Acute and chronic effects of organic solvents on the central nervous system. Use of psychobehavioral performance tests in the assessment of toxicity]. AB - Neurotoxicity of organic solvents is one of the most important emerging issues in the field of occupational health. Psychological testing has been proven useful not only in clinical diagnosis but also in experimental and epidemiological studies. Although various psychobehavioral performance test batteries have been applied in the study of neurotoxicity of organic solvents during these last two decades among European countries and America, only few studies have been made on these in Japan. It is therefore considered very important to review the major papers published to date, clarify the issues being currently discussed, and propose important studies for future. The present paper provides a review of the results obtained by the application of behavioral performance tests in the study of solvent toxicity. The studies reviewed are classified into the following five parts: 1. psychological test batteries developed to date, 2. human experimental studies and experimental field studies on the acute toxicity of organic solvents, 3. epidemiological studies on industrial workers, 4. characteristics of the central nervous system dysfunction caused by organic solvents, and 5. prognosis of workers diagnosed as chronic organic solvent intoxication. The paper also discusses the applicability of psychobehavioral techniques and addresses issues in data collection in the study of the effects of solvent exposure on the nervous system. PMID- 2187104 TI - [Prevention of microbial contamination of surgical wounds]. AB - Comparative analysis of 3707 operations on the organs of the abdominal cavity has shown the significant advantage of the suggested by the authors method for intraoperative wound protection with latex rubber in combination with placing the longitudinal removable sutures over the subcutis and skin, and dressing-free management of the wounds in prophylaxis of the postoperative purulent wound complications. After 310 operations of different contamination degree performed with the use of the given method, no suppuration of the operative wounds was noted. PMID- 2187105 TI - [Treatment of experimental suppurative wounds with proteolytic and lytic enzymes immobilized on carbonic cloth]. AB - When in the experiment on rats the jointly immobilized on a carbonic cloth proteases and lytic enzyme complex were used, the reduced period of the suppurative wound cleaning and healing was noted as compared to that in use of the immobilized on a carbonic cloth proteases and jointly immobilized on a gause proteases and lytic enzyme complex. PMID- 2187106 TI - [Experience with and the prospects of using a single polypropylene thread in surgery of suppurative wounds]. AB - A polypropylene monofilament in placing secondary sutures causes minimal damages in the tissues. The absence in a monofilament of the capillary-filtrative properties prevents the development of infiltrate, suppuration, dehiscence of the wound edges. In using a modified suture of the granulating wound, suggested by the authors, a good cosmetic and functional effect was noted. PMID- 2187107 TI - [Bacteriocholia and antibiotic prevention of postoperative suppurative-septic complications in patients with inflammatory diseases of the biliary tract]. PMID- 2187108 TI - [Various problems of the prevention of suppurative-inflammatory complications after surgery of the abdominal organs]. PMID- 2187109 TI - [Use of laser rays in ambulatory surgery]. PMID- 2187110 TI - [Use of lasers in the surgical treatment of suppurative pilonidal cysts]. PMID- 2187111 TI - [Forceps to facilitate the placement of sutures]. PMID- 2187112 TI - Enhancement of endocrine pancreatic secretions by essential fatty acids. AB - Recent studies have suggested the beneficial effects of essential fatty acids in postoperative patients receiving total parenteral nutrition. While there is abundant information on the role of glucose and amino acids on insulin release, the effect of essential fatty acids on endocrine pancreatic secretions is not clear. Since linoleic and linolenic acids are constituents of TPN solutions as well as dietary fat, our aim was to examine their effect on the endocrine pancreatic function, using isolated islets. In each experiment, six islets microdissected from three mice were preperifused at the rate of 1 ml/min with Krebs-Ringer bicarbonate (KRB) buffer pH 7.4 containing 2% bovine albumin and 5.5 mM glucose (basal) with continuous supply of 95%/5%, O2/CO2 for 1 hr, after which basal samples were collected on ice every minute. The perifusion was continued for 20 min after the addition of a mixture of 10 mM linoleic acid and 5 mM linolenic acid to the KRB. During each perifusion phase, effluent samples were also collected for insulin and glucagon assay. The mean integrated area under the curve/20 min showed an increase in both insulin and glucagon secretions with the addition of fatty acids. Hence insulin increased from a basal 3154.8 +/- 953.7 to 8393.0 +/- 2073.1 pg (P less than 0.025, n = 6) and glucagon increased from 193.7 +/- 46.9 to 1566.1 +/- 411.2 pg (P less than 0.0025, n = 5). The fatty-acid induced insulin but not glucagon secretion was blocked by the addition of 2 mM palmoxirate an inhibitor of fatty acid oxidation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2187113 TI - Kupffer cell:hepatocyte cocultures release nitric oxide in response to bacterial endotoxin. AB - Nitric oxide (NO.) is a short-lived intermediate in a biochemical pathway where L arginine is converted to L-citrulline and nitrite/nitrate (NO2-/NO3-). This highly reactive molecule is the biologically active component of this inducible pathway in macrophages. Using a rat Kupffer cell:hepatocyte (KC:HC) coculture model, we have previously shown that this combination of cells produces large quantities of both citrulline and NO2-/NO3- if exposed to lipopolysaccharides (LPS) but we did not determine whether nitric oxide was produced or released. We had also shown that this L-arginine metabolism was associated with a profound decrease in total protein synthesis. In these experiments, we show that KC:HC cocultures release nitric oxide into the culture supernatant if exposed to LPS. NO. production by these cells requires L-arginine and is inhibited by NG-mono methyl-L-arginine. In addition, the time course for NO. release by KC:HC cocultures parallels the previously reported time course for NO2-/NO3- synthesis and the decrease in protein synthesis, supporting the hypothesis that NO. is the reactive nitrogen intermediate of the pathway responsible for this inhibition of protein synthesis. Finally, we show that KC:HC cocultures release more NO. than KC alone in response to LPS, and we propose that the combination of KC and HC acts as a functional unit capable of generating large amounts of NO. from L arginine in gram-negative sepsis. PMID- 2187114 TI - The effect of plaque composition on laser recanalization. AB - Laser recanalization using metal-capped laser fibers and continuous-wave laser energy occurs by thermal ablation of atherosclerotic plaque. Different types of plaque respond differently to laser energy and plaque composition may be an important determinant of the success of laser recanalization. To investigate this hypothesis, 16 patients with symptomatic arterial occlusions in the mid and distal superficial femoral artery underwent B-mode ultrasound arterial imaging prior to attempted argon laser recanalization. The composition of the occlusions was classified as soft (echogenicity less than the adjacent arterial wall), dense (echogenicity equal to the adjacent arterial wall), or calcified (echoreflective). Recanalization was successful in 100% (8/8) of patients with soft occlusions versus 38% (3/8) with dense or calcified occlusions (P = 0.01). Thus, plaque composition as assessed by B-mode ultrasound imaging appears to be an important predictor of the success or failure of arterial recanalization using a thermal laser probe. PMID- 2187115 TI - The role of glutamine in maintaining a healthy gut and supporting the metabolic response to injury and infection. AB - In the critically ill surgical patient a variety of therapeutic maneuvers is required to maintain a "healthy gut." Provision of adequate amounts of glutamine to the gastrointestinal mucosa appears to be just one of these maneuvers. Other methods utilized to protect the gut from becoming a wound include: (a) minimizing additional systemic insults (such as hypotension, sepsis, multiple operative procedures); (b) aggressive pulmonary care; (c) the judicious use of antibiotics; and (d) aggressive enteral or parenteral feedings. The concept that the gut is an organ of quiescence following surgical stress merits reconsideration. The intestinal tract plays a central role in interorgan glutamine metabolism and is a key regulator of nitrogen handling following surgical stress. Critically ill patients are susceptible to developing gut-origin sepsis, the incidence of which will be diminished by instituting measures and providing treatments which support intestinal structure, function, and metabolism. Provision of glutamine-enriched diets to such patients may be one of these therapies. PMID- 2187116 TI - A mathematical model for insulin kinetics. II. Extension of the model to include response to oral glucose administration and application to insulin-dependent diabetes mellitus (IDDM). AB - A generalized nonlinear mathematical model which incorporates beta-cell kinetics, a glucose-insulin feedback system and a gastrointestinal absorption term for glucose, is presented. Numerical simulations using this model lead to time variations of plasma glucose and insulin levels that are consistent with clinical observations in normal groups. The results obtained after suitable reduction in some of the parameters are in agreement with the clinical profile and laboratory data in insulin-dependent diabetes mellitus (IDDM). Linear stability analysis of the equations shows that there is a change in the nature of the stability in the transition from the normal case to IDDM, and it is the decrease in the beta cell function which causes this change. PMID- 2187117 TI - Potentiating effect of granulocyte-macrophage colony-stimulating factor on interleukin-1-induced thymocyte proliferation: evidence for an interleukin-2 and tumor necrosis factor-independent pathway. AB - The effect of Colony-Stimulating Factors (CSFs) on the growth of murine thymocytes was investigated. None among the following factors tested alone, i.e., Interleukin-3 (IL-3), Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), Granulocyte Colony-Stimulating Factor (G-CSF) or Macrophage Colony-Stimulating Factor (M-CSF) has been found to stimulate thymidine uptake by thymocytes. However, GM-CSF synergistically enhances thymocyte proliferation induced by Interleukin-1 (IL-1). Synergistic responses are obtained at a very pronounced level after 3 days of culture with very low factor concentrations (1.5 to 15 pM) and in the complete absence of mitogen. Similar effects are induced by IL-3, though to a lesser degree. In contrast, neither G-CSF nor M-CSF potentiate thymocyte proliferation promoted by IL-1. Kinetic studies show that the synergy between IL-1 and GM-CSF reaches its maximum after about 72 h of thymocyte culture and that it requires the simultaneous presence of both factors during the first 24 h. In addition, our data suggest that GM-CSF acts in synergy with IL-1 by an Interleukin-2 (IL-2)-independent pathway since: (i) incubation of thymocytes with GM-CSF in the presence of IL-1 does not significantly enhance the expression of the IL-2 receptors (IL-2R) as demonstrated by flow cytometry, and, (ii) specific monoclonal antibodies against murine IL-2 or IL-2R fail to reduce thymocyte proliferation in response to the synergistic combination. Similarly, the potentiating effect of GM-CSF on IL-1 thymocyte growth does not depend on Tumor Necrosis Factor alpha (TNF) since (i) the synergy for IL-1 and GM-CSF and that previously described for IL-1 and TNF cumulate and (ii) anti-TNF antibodies do not abolish the potentiating effect of GM-CSF. PMID- 2187118 TI - Identification of TNF-LT blocking factor(s) in the serum and ultrafiltrates of human cancer patients. AB - Human serum ultrafiltrate (UFS) obtained from cancer patients contains material(s) which inhibit the cytolytic activity of tumor necrosis factor (TNF alpha) and lymphotoxin (LT-TNF-beta) in vitro. These factors are found in UFS from patients with different types of cancers and are not detected in the sera of normal donors. Results from molecular sizing studies demonstrated that their molecular weights are over 30 kD. They appear to block by interfering with the early stages of cell lysis. It is not clear whether or not these TNF-LT blocking factor(s) are the same molecules. These factors may have adverse effects on the biological activities of TNF and LT in cancer patients. PMID- 2187119 TI - Quality of ambulatory care. Epidemiology and comparison by insurance status and income. AB - In this report the data from medical history questionnaires, screening examinations, insurance claims, and a face-to-face physician interview were used to examine the quality of ambulatory care received for 17 chronic conditions by a general population of 5986 adults (less than or equal to 65) and children (less than or equal to 14) enrolled in the RAND Health Insurance Experiment. Subjects in six U.S. sites were randomly assigned to insurance plans that were free or that required cost sharing, or in one site to an HMO. Quality-of-care criteria- both process (what was done to patients) and outcome (what happened to them)- were developed. Overall, 81% of outcome criteria and 62% of process criteria were met. Physicians interviewed patients with selected conditions at the Experiment's end to evaluate care. They suggested that approximately 70% of patients should have their current therapy changed, but only 30% of patients would obtain more than minor improvement from such a change. Clinically meaningful plan differences in quality of care were observed only for the process criteria dealing with the need for a visit (free plan compliance 59%; cost sharing compliance 52%). Quality of care for the poor was slightly worse than for the nonpoor and persons randomized to an HMO had slightly better overall quality of care than those in the fee-for-service system. Substantial improvements in the quality of the process of care could be made, but impact on outcome may be small. Results of the analysis suggest the need for development of clinical models to test the relationship between specific process criteria and improvements in outcome. PMID- 2187120 TI - Etoposide and teniposide in the treatment of acute leukemia. AB - Etoposide and teniposide are semi-synthetic glucoside derivatives of podophyllotoxin with a documented anti-tumour activity in various types of malignant diseases. It was an early observation that these epiphodophyllotoxins were efficacious in hematological malignancies such as lymphomas and leukemias. In this report the clinical evidence supporting the activity of etoposide and teniposide in acute lymphoblastic (ALL) and non-lymphoblastic leukemia (ANLL) is reviewed. Unlike podophyllotoxin, etoposide and teniposide do not appear to affect microtubular function nor arrest cells in mitosis. These epiphodophyllotoxins, like other DNA intercalating agents, have topoisomerase II as their target. Most studies with etoposide have been performed in ANLL and with teniposide in ALL. This choice seems to be rather arbitrary and is better explained by traditional reasons than actual study results. The data in acute leukemias are partly flawed by the absence of certain prospective comparative trials. However, the current information on etoposide clearly shows that this agent has substantial activity in ANLL and may well be incorporated into front line regimens and the same is true for teniposide in the treatment of ALL. Nevertheless, based on available literature, there are no convincing data to the author's mind to support that one of these agents is superior to the other in the treatment of acute leukemias. PMID- 2187121 TI - Immunocytochemical evaluation of abl-gene products in leukemic cell lines. AB - We raised monoclonal antibody (MAb) against a synthetic oligopeptide corresponding to a portion of the predicted v-abl protein sequence (379-390). This MAb reacted with all of the abl-gene products (p145c-abl, p150c-abl and p210bcr-abl fused protein) and was not specific for any one of them. Immunocytochemically, we investigated the expression and localization of the abl gene products in various leukemic cell lines. Positive immunoreactions were observed in Ph1 positive leukemic cell lines (K562 and KU-812) and erythro leukemic cell lines (HEL and K3D) and were located on the cell membrane. Electron microscopically, a different distribution pattern was observed among the cell lines: linear and almost even in Ph1 positive leukemic cell lines, whereas spotted or budding-like in erythroleukemic cell lines. Ph1 translocation produces p210bcr-abl fused protein with not only altered autophosphorylation activities but also altered subcellular distribution patterns. PMID- 2187122 TI - Correlation between laminin and type IV collagen distribution in breast carcinomas, and estrogen receptors expression, lymph node and vascular involvement. AB - The laminin (Lam) and type IV collagen (Coll IV) and estrogen receptor (ER) immunodetections were assessed in a large series of 400 human breast carcinomas. In all the cases the patient's age, the tumor size, the histological type and grade, the presence or the absence of axillary lymph node metastasis and of vascular invasion in tumor borders, and ER tumor content were recorded. Monoclonal anti-Lam, anti-Coll IV were applied with the avidin-biotin-peroxidase complex and monoclonal anti ER with peroxidase anti-peroxidase complex, on frozen sections. A computerized system of image analysis referred to as SAMBA (TITN) with specific software for tissue sections analysis permitted a multiparametric quantitative analysis of immunostained surfaces. With this system, in each tumor, the cellularity, the percentage of Lam, Coll IV and receptor positive surfaces versus the total cell surface and versus the epithelial (keratin positive) surface, the integrated optical density IOD histograms were obtained and correlated to morphometrical and standard histological data. From this study, it was shown that: (1) Lam and Coll IV immunostained epithelial basement membranes in carcinomas were correlated to the presence of estrogen and progesterone receptor antigenic sites within the tumors, with a significant decrease of the positive staining in ER-ICA negative tumors in comparison to ER-ICA/PR-ICA positive tumors. (2) The combined densitometric and morphometric evaluation demonstrated a decrease of Lam and Coll IV immunostaining in malignant tumors, correlated to (i) the presence of peritumorous vascular invasion and (ii) keratin positive cells in bone marrow (iii) axillary lymph node involvement. It is concluded that the variations in Lam and Coll IV antigens distribution may be relevant indicators of tumor metastatic potential in breast carcinomas and that computerized image analysis enables the standardization of the evaluation antigens distribution. PMID- 2187123 TI - Cumulative bone marrow stromal damage caused by X-irradiation and cytosine arabinoside in leukemic mice. AB - A study of treated murine acute myeloid leukemia (AML) with an emphasis on the bone marrow stromal function is reported. Leukemia was induced in C57Bl mice through intraperitoneal (i.p.) inoculation of C-1498 myelogenous leukemic cells. The leukemic mice were administered: (1) total body lethal X-irradiation (t.b.i.); (2) two i.p. cytosine-arabinoside (Ara-C) injections followed by X irradiation. Control mice received similar regimens. Bone marrow of experimental and control mice was processed for stromal cell cultures (SCC) and in vitro engraftment of hematopoietic cells onto the cultures. The results of this study indicate that the bone marrow stromal deficiency which occurs in leukemia is aggravated by Ara-C and irradiation treatments. Moreover, SCC of treated leukemic mice sustain in vitro hematopoiesis only to a limited degree. Stromal deficiency, as possible cause for graft failure in bone marrow transplanted leukemic patients, is discussed. PMID- 2187124 TI - Risk for malignant tumors after oral contraceptive use: is it related to organ size while taking the pill? PMID- 2187125 TI - O'Connorite Bedlam: Feargus and his grand-nephew, Arthur. PMID- 2187126 TI - Yellow fever in Rio de Janeiro and the Pasteur Institute Mission (1901-1905): the transfer of science to the periphery. PMID- 2187128 TI - In spite of medical help: the puzzle of an eighteenth-century Prime Minister's illness. PMID- 2187127 TI - Reproductive performance on the Maltese Islands during the Second World War. PMID- 2187129 TI - Texts and documents. Translation and analysis of a cuneiform text forming part of a Babylonian treatise on epilepsy. PMID- 2187130 TI - Illustrations from the Wellcome Institute Library. Sir Henry Dale's laboratory notebooks, 1914-1919. PMID- 2187131 TI - [Morals, the mass media and blood pressure determination]. PMID- 2187132 TI - [Nevi are common--they should be treated accordingly]. PMID- 2187133 TI - [Physiology of the peritoneum--a review]. PMID- 2187134 TI - [The man behind the syndrome. Harold Sheehan. Study of the mechanism behind postpartum necrosis of the hypophysis]. PMID- 2187135 TI - [Cytologic endometrial diagnosis can improve the quality of health care]. PMID- 2187136 TI - [Nerve growth factor as a therapeutic agent: transplantation of brain tissue as a possible treatment of neurodegenerative disorders]. AB - An account of experiments focused on the treatment of neurodegenerative disease by means of cell grafts, in which genetically modified cells that release abundant nerve growth factor are described, and their transplantation to the rat brain reported. The cells can survive in the rat brain and exert potent effects on cholinergic neurons both in the host cortex, basal forebrain and striatum, and in tissue grafts. PMID- 2187137 TI - [Centrifugal pumps for forcing blood: technical aspects (review)]. AB - The paper is concerned with one of the trends in the design of outfits for blood forcing, namely with centrifugal pumps. Advantages and shortcomings of such pumps are assessed as compared to roller and other type pumps for blood. Unsolved problems are outlined. Based on a comparative analysis, six main designs are distinguished, the principles of the action, the scope of uses and characteristics are depicted. The conclusion is made that this type of pumps holds promise for the use in cardiosurgical clinics of the USSR. PMID- 2187138 TI - [The use of photographic materials as a dry reagent for determining the peroxidase activity of biological preparations]. AB - A new method is reviewed for measuring the peroxidase activity of biopreparations using light quantum-sensitized photographic material as a detector. The method involves the combination of the reactions of peroxidase oxidation of hydroquinone, a constituent part of the developing solutions, by hydrogen peroxide and photochemical interaction of the remaining hydroquinone with silver halogenides of the photoemulsion layer. Visually, up to 2 ng/ml of horse radish peroxidase is detectable. On photometry of the spots obtained, the limit of peroxidase demonstration amounts to 0.6 ng/ml. The data obtained during measurements of the peroxidase activity of the saliva, blood serum, plant extracts and immunoenzymic conjugates are provided. PMID- 2187139 TI - [The EOM-24 echo-ophthalmometer]. PMID- 2187140 TI - [Microprocessor controllers in portable ultrasonic diagnostic units]. AB - Application possibilities of the unified microprocessor module, which allows one to widen ultrasound diagnostic unit's parameters, have been considered herein: i.e. maintenance of the unit's functional keyboard, output of the alphabet digital information, cursor, markers on the monitor screens, monitoring of the movement of markers and cursor all around the screen, calculation of the distance between them, monitoring of the unit's modes, calculations of the table data based parameters and established formulas. The tasks fulfilled by the microprocessor module could be fulfilled when more up-to-date ultrasound units are designed. PMID- 2187141 TI - Functions of the flagellar modes of rotation in bacterial motility and chemotaxis. AB - Bacteria swim by rotating their flagella, the rotation being due to a motor located at the base of each flagellum. In this paper the correlation between motor function and mode of swimming is reviewed, with special emphasis on recent data that indicate that the motor is a three-state device. Novel findings with regard to the motor function and bioenergetics are surveyed, and mechanisms are proposed to account for these findings. PMID- 2187142 TI - Mapping of sequenced genes (700 kbp) in the restriction map of the Escherichia coli chromosome. AB - This paper describes software (written in Pascal and running on Macintosh computers) allowing localization of unknown DNA fragments from the Escherichia coli chromosome on the restriction map established by Kohara et al. (1987). The program identifies the segment's map position using a restriction pattern analysis obtained with all, or some, of the eight enzymes used by Kohara et al. (1987). Therefore, the sequenced genes available in the EMBL library may be localized on the E. coli chromosome restriction map. This allowed correction of the map (mainly by introducing missing sites in the published maps) at the corresponding positions. Analysis of the data indicates that there is only a very low level of polymorphism, at the nucleotide level, between the E. coli K12 strains used by the various laboratories involved in DNA sequencing. The program is versatile enough to be used with other genomes. PMID- 2187143 TI - Cloning and characterization of mepA, the structural gene of the penicillin insensitive murein endopeptidase from Escherichia coli. AB - The putative structural gene mepA of the penicillin-insensitive murein endopeptidase from Escherichia coli was cloned and sequenced. N-terminal sequence determination with the isolated endopeptidase protein showed that this enzyme is coded by the mepA gene and that it is synthesized initially with an N-terminal signal peptide. No significant sequence homology with the other (penicillin sensitive) murein endopeptidase (dacB) or any other protein was found. The precise chromosomal mapping position of mepA relative to two other genes, aroC and fabB, was shown to be 50.4 min. E. coli strains carrying multicopy plasmids with the mepA gene produced 5-6-fold more endopeptidase and secreted it into the periplasm, where it appeared to function normally in vivo since the release of cell wall peptides into the medium increased in parallel. The transformed cells were, however, not unusually sensitive to penicillin and their murein had a normal degree of cross-bridges. PMID- 2187144 TI - Nucleotide sequence and expression of an operon in Escherichia coli coding for formate hydrogenlyase components. AB - An 8kb segment of DNA from the 58/59 min region of the E. coli chromosome, which complements the defect of a mutant devoid of hydrogenase 3 activity, has been sequenced. Eight open reading frames were identified which are arranged in a transcriptional unit; all open reading frames were transcribed and translated in vivo in a T7 promoter/polymerase system. Analysis of the amino acid sequences derived from the nucleic acid sequences revealed that one of them, open reading frame 5 (ORF5), exhibits significant sequence similarity to conserved regions of the large subunit from Ni/Fe hydrogenases. Two of the open reading frames (orf2, orf6) code for proteins apparently carrying iron-sulphur clusters of the 4Fe/4S ferredoxin type. The product of one of the open reading frames, orf7, displays extensive sequence similarity with protein G from the chloroplast electron transport chain. ORF3 and ORF4, on the other hand, are extremely hydrophobic proteins with nine and six putative transmembrane helices, respectively. Over a limited hydrophilic sequence stretch, bordered by putative transmembrane areas, ORF3 and ORF4 exhibit homology with subunits 4 and 1 of mitochondrial and plastid NADH-ubiquinol oxidoreductases, respectively. The operon described, therefore, appears to comprise genes for redox carriers linking formate oxidation to proton reduction and for a hydrogenase of hitherto unique composition. PMID- 2187145 TI - Export and processing analysis of a fusion between the extracellular heat-stable enterotoxin and the periplasmic B subunit of the heat-labile enterotoxin in Escherichia coli. AB - As an initial approach in the study of the mechanism of secretion of the extracellular heat-stable enterotoxin of Escherichia coli (STA), and in order to use this polypeptide as an extracellular carrier we previously constructed a fusion between the complete STA toxin (pre-pro-STA) and the mature B subunit of the periplasmic heat-labile enterotoxin (LTB); the resulting STA-LTB hybrid was not secreted to the extracellular environment, and cells expressing the hybrid lysed at temperatures above 35 degrees C. In this work we have established that the hybrid is initially detected as pre-pro-STA-LTB and converted to pro-STA-LTB, which lacks the 19 amino acids that share the properties of a signal peptide; the sequenced 17 amino-terminal residues of pro-STA-LTB defined the processing site of pre-pro-STA-LTB at pro-3phe-2ala-1 decreases gln+1. This process was sensitive to an energy uncoupler (CCCP) and was correlated with translocation of pro-STA LTB across the inner membrane. Additionally, we are able to show that although pre-pro-STA-LTB is processed at 37 degrees C and 29 degrees C, it is more efficiently processed at the latter temperature. At 37 degrees C, pro-STA-LTB was poorly released into the periplasm, resulting in accumulation of this protein, pre-pro-STA-LTB, and pre-beta-lactamase in the inner membrane, and in cell lysis. In contrast, at 29 degrees C pro-STA-LTB was localized in the periplasm and in the inner membrane, and pre-pro-STA-LTB and pre-beta-lactamase did not accumulate; however, translocation of periplasmic pro-STA-LTB across the outer membrane still did not occur, and a second processing step that would eliminate the pro segment from pro-STA-LTB was never observed. Thus, the fusion of pre-pro STA and LTB resulted in a polypeptide that, while incompatible with secretion to the extracellular medium, is exported to the periplasm in a temperature conditional fashion. This latter observation is consistent with an STA secretion pathway whereby pre-pro-STA is first processed to periplasmic pro-STA by the removal of a 19-amino-acid signal peptide. PMID- 2187146 TI - Two precursors of the heat-stable enterotoxin of Escherichia coli: evidence of extracellular processing. AB - Expression of the gene of the methanol-soluble, heat-stable enterotoxin of Escherichia coli (STA) allowed the identification by SDS-PAGE of a cell associated 7500 Dalton STA-related peptide; when similar experiments were performed with a phosphate buffer SDS-PAGE system, an additional Mr 9800 band became apparent. The 9800 Dalton form, pre-pro-STA, accumulated as an intracellular species when the experiments were performed in the presence of the proton ionophore CCCP (carbonylcyanide m-chlorophenylhydrazone); by pulse-chase experiments, it was shown that pre-pro-STA became a periplasmic Mr 7500 pro-STA and this form was chased to the culture supernatant; periplasmic and extracellular pro-STA showed the same electrophoretic mobility. A short time after the pulse, pro-STA was converted extracellularly to mature STA (Mr 4500). It is proposed that STA is synthesized as pre-pro-STA, a 72-amino-acid peptide that is subsequently cleaved between amino acids 19 and 20 as it is translocated across the inner membrane. The resulting 53-amino-acid pro-STA is first detected in the periplasm and is then secreted to the culture supernatant. Pro-STA is cleaved extracellularly to yield mature STA (Mr 4500). PMID- 2187147 TI - A 59 kiloDalton outer membrane protein of Salmonella typhimurium protects against oxidative intraleukocytic killing due to human neutrophils. AB - We have isolated a Salmonella typhimurium (ST) mutant, JKS400, deficient in the production of a surface-exposed outer membrane protein (Omp) and phenotypically hypersensitive to the oxidative antimicrobial mechanism of polymorphonuclear leukocytes (PMNs). This Omp migrated at approximately 59 kiloDaltons (kD) in sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). We found with P22 transduction that the capacities to produce the protein and to exert wild-type resistance to oxidative killing were tightly linked. Transduction of JKS400 with a P22(HT)int- bacteriophage grown on a Tn10 insertion library in LT2 yielded tetracycline-resistant isolates that had been returned to wild-type protein production. Further experiments showed that restoration of protein production was accompanied by restoration of the parental resistance phenotype to killing by PMNs and by restoration to wild-type resistance to H2O2. The map position of the Tn10 was determined to be at 96 minutes in the Salmonella chromosome. This protein appears to behave as a virulence factor, promoting the capacity of Salmonella typhimurium LT2 to survive oxygen-dependent killing mechanisms in neutrophils. PMID- 2187149 TI - Computer assisted screening for alcohol-related problems in a general hospital setting. PMID- 2187148 TI - Effect of positive redox potentials (greater than +400 mV) on the expression of anaerobic respiratory enzymes in Escherichia coli. AB - The expression of fumarate reductase and other enzymes of anaerobic respiration in Escherichia coli was studied as a function of the redox potential (Eh) in the medium. Redox potentials up to +300 mV allowed full expression of fumarate reductase (frd) genes. Higher values resulted in decreased expression. The relationship between Eh and expression of frd could be approximated by the Nernst equation, assuming a redox couple with a midpoint potential Eo' = +400 mV to 440 mV. At Eh values greater than +510 mV (generated anaerobically by hexacyanoferrate(III] the degree of repression was the same as that obtained by O2. Hexacyanoferrate(III) also caused decreased activities of dimethylsulphoxide (DMSO), nitrite and nitrate reductases. Since expression of these enzymes depends on FNR, the gene activator of anaerobic respiratory genes, it is suggested that the function of FNR is controlled by a redox couple of Eo' = +400 mV to 440 mV. PMID- 2187150 TI - Should all pregnant women be offered an ultrasound examination? PMID- 2187151 TI - An autonomously replicating sequence from HeLa DNA shows a similar organization to the yeast ARS1 element. AB - A HeLa DNA fragment, which may function as an anchorage point to the nuclear matrix for human chromosomes 1 and 2, also functions as an autonomously replicating sequence (ARS) in the yeast Saccharomyces cerevisiae. In the present report we show that this DNA fragment contains both bent DNA and an A-T rich region which appear to be associated with the ARS function. More interestingly, DNA sequence analysis shows that the spatial distribution of these features is strikingly similar to that found in the yeast ARS1 element. PMID- 2187152 TI - Regulation of the phosphate regulon of Escherichia coli: properties of phoR deletion mutants and subcellular localization of PhoR protein. AB - The phoR gene is a bifunctional regulatory gene for the phosphate regulon of Escherichia coli. It acts as a negative regulator in the presence of excess phosphate and as a positive regulator with limited phosphate, through modification of PhoB protein. We constructed several phoR genes, with various deletions in the 5' regions, which were regulated by the trp-lac hybrid promoter. The PhoR1084 and PhoR1159 proteins that lack the 83 and 158 N-terminal amino acids, respectively, retained the positive function for the expression of phoA that codes for alkaline phosphatase, but lacked the negative function. The PhoR1263 protein that lacks the 262 N-terminal amino acids was deficient in both functions. An antiserum against PhoR1084 protein was prepared. Western blot analysis of the subcellular fractions obtained by differential centrifugation indicated that the intact PhoR and PhoR1084 proteins are located in the inner membrane and cytoplasmic fractions, respectively. The results suggest that PhoR protein is anchored to the cytoplasmic membrane by the amino-terminal region. PMID- 2187153 TI - A mutation affecting amdS expression in Aspergillus nidulans contains a triplication of a cis-acting regulatory sequence. AB - In Aspergillus nidulans expression of the acetamidase structural gene, amdS, is under the control of at least four regulatory genes including the trans-acting amdA regulatory gene. A cis-acting mutation (amdI66) consisting of an 18 bp duplication in the 5' region of the amdS gene results in very high levels of acetamidase activity but only in strains carrying semi-dominant mutations in the amdA gene. In selecting for increased amdS expression in an amdI66 and A+ strain, an A. nidulans strain with a mutation in the 5' region of the amdS gene was isolated. The nucleotide sequence was determined of the region containing the mutation, designated amdI666. The mutant strain carries three tandem copies of the 18 bp sequence that is duplicated in the amdI66 mutation. Thus, from a strain carrying a duplication of an apparent regulatory protein binding site with little effect on gene expression, a strain has been derived that carries a triplication of the site with consequent major effects on regulation. The multiple copies of regulatory sites present in many genes may have been generated by a similar mechanism. PMID- 2187154 TI - Measurement of in vivo expression of nrdA and nrdB genes of Escherichia coli by using lacZ gene fusions. AB - By using a promoter probe plasmid we investigated expression of the linked nrdA and nrdB genes coding for the two different subunits of the ribonucleoside diphosphate reductase enzyme of Escherichia coli. For this reason, nrdA-lacZ, nrdAB-lacZ and nrdB-lacZ fusions were constructed. Results obtained indicate that the nrdB gene has a promoter from which it may be transcribed independently of the nrdA gene. Furthermore, the nrdB gene may also be transcribed from the nrdA promoter. The expression of the nrdB gene is about 14-fold higher from the nrdA promoter than from its own promoter. The induction of both nrdA and nrdB genes by DNA-damaging agents in the wild-type strain as well as in several SOS mutants was also studied; nrdA gene expression was increased by these treatments in RecA+, RecA-, and LexAInd- strains, although in both RecA- and LexAInd- mutants the nrdA gene expression was considerably lower than that in RecA+ cells. nrdB gene expression was stimulated by DNA damage only when its transcription was from the nrdA promoter, but there was no effect when nrdB was transcribed from its own promoter. In addition, the basal level of nrdA-lacZ and nrdAB-lacZ fusions was reduced in strains containing either RecA- and LexAInd- mutations or a multicopy plasmid carrying the lexA+ gene, whereas the presence of a LexA51Def mutation increased the constitutive expression of both fusions. On the contrary, the basal level of the nrdB-lacZ fusion remained constant in all these strains. Together these results indicate that induction of the SOS response enhances expression of the nrd genes from the nrdA promoter. PMID- 2187155 TI - A multipurpose broad host range cloning vector and its use to characterise an extracellular protease gene of Xanthomonas campestris pathovar campestris. AB - A multipurpose broad host range plasmid, pIJ3200, was constructed by inserting the polylinker-containing 445 bp PvuII fragment of Bluescript M13 into the EcoRI site of the cosmid pLAFR1. Using this vector a protease gene of Xanthomonas campestris pathovar campestris, previously cloned in the recombinant plasmid pIJ3070, was located by deletion to a 2.2 kb DNA region. Sequencing of the protease gene revealed an open reading frame encoding a 580 amino acid polypeptide with molecular weight of 57,000. The deduced amino acid sequence showed strong homology with the subtilisin family of serine proteases. This, together with its sensitivity to inhibition by phenylmethylsulphonyl fluoride, suggests that the enzyme belongs to this family of proteases. PMID- 2187156 TI - Regulation of proline utilization in Salmonella typhimurium: how do cells avoid a futile cycle? AB - Salmonella typhimurium can degrade proline for use as a carbon, nitrogen, or energy source. To determine whether a futile cycle occurs which degrades the proline accumulated by proline biosynthesis, we studied the expression and enzymatic activity of the proline utilization (put) pathway under conditions which increase the concentration of the intracellular proline pools: catabolism of the dipeptide glycyl-proline, overproduction of proline due to a mutation which prevents feedback inhibition of proline biosynthesis, and accumulation of proline due to osmotic stress. The results indicate that: (i) internal proline induces the put genes, but only when accumulated to concentrations greater than the normal proline biosynthetic pool; and (ii) degradation of proline pools accumulated under high osmotic pressure is limited because proline oxidase is directly inhibited under these conditions. PMID- 2187157 TI - [Tretinoin; promise for eternal cutaneous youth?]. PMID- 2187158 TI - Brain abscess in Saudi Arabia. AB - There are significant variations among countries in the incidence of brain abscess. We report here 26 cases of brain abscess treated at the Neurosurgery Department of King Faisal University and Dammam Central Hospital Saudi Arabia over a six year period (1982-1988). This is 2.3% of total admissions to the two neurosurgery departments serving a population of approximately 1.2 million in the same period. Young males were most often affected (M/F ratio 3.3:1; 31% were less than 15 years old, 46% aged between 15-39 years, and 23% older than 40 years). Streptococcus was found to be the most common microorganism (38.4%). Mixed infection was seen in 15.3%, and sterile abscesses were found in 11.5% of the patients after aerobic and anaerobic cultures of the pus. Chronic otitis media and paranasal sinusitis predisposed the patients to abscess formation in 57.6% of the cases. The temporo-parietal area was the commonest site. Epilepsy was a complication in 30.7% of our patients, and the mortality rate was 15.3%. PMID- 2187159 TI - Involvement of the orbit in diseases of the paranasal sinuses. AB - A brief description of the anatomical relationship between the orbit and the paranasal sinus system is given. Sinus infections, celes, and tumors which can lead to orbital complications are described. PMID- 2187160 TI - Multimodality evoked potentials and early prognosis in comatose patients. AB - In 112 comatose patients somatosensory, visual and auditory evoked potentials were registered within 36 hours after the onset of coma or admission. Main causes of coma were head injury, and intracerebral and subarachnoid haemorrhage. The initial bilateral loss of any evoked potential was associated with a mortality of 98%. Normal somatosensory evoked potentials were associated with a survival rate of 74%, while normal visual and normal auditory evoked potentials had a survival rate of 60% and 66%, respectively. It is concluded that SEPs can be valuable for the prognosis of coma after primary brain lesions. PMID- 2187161 TI - Spinal metastases of intracranial ependymomas. Four case reports and review of the literature. AB - Intracranial ependymomas tend to spread along on the liquor pathways and thus to seed subarachnoid metastatic implants. According to autopsy data, spinal seeding can be expected in 25% of cases subsequent to surgery of the primary tumor. Analysis of four of our own cases (out of 125 primary intracranial ependymomas) together with those described in the literature suggests clinical evidence of seeding in 75% of patients. 47 of 75 metastases originated from malignant infratentorial ependymomas. Malignant ependymomas metastasize earlier than benign ones. They are characterized by disseminated seeding of tumor implants along the entire spinal subarachnoid space. The median survival time after diagnosis of seeding was 6 months. 80% of all patients died within the first 12 months following diagnosis. The necessity of prophylactic spinal radiation therapy in the course of the initial treatment of intracranial ependymomas has not yet been proven. PMID- 2187162 TI - Lower limb compartment syndrome following lumbar discectomy in the knee-chest position. AB - We report on two cases of compartment syndrome following lumbar discectomy in the knee-chest position. This complication has only been described once since 1953. Seven cases of compartment syndrome following other surgical procedures were found in the literature. Any increases in tissue pressure of a muscle compartment exceeding 35-40 mmHg over a longer period of time can result in this complication for example, too tight cast, space-occupying intrafascial bleeding, or postischemic swelling. The diagnosis is purely clinical and is based on the typical combination of extremely painful edema with rapid onset of sensory loss and subsequent motor deficits. The muscle necrosis leads to myoglobinaemia and myoglobinuria, recognizable by brown urine. The therapy consists of urgent fasciotomy of swollen compartments without skin suture. The prognosis is highly dependent on the time of the surgical decompression: within 6 hours serious deficits are avoidable; after 24 hours irreversible necrosis of muscle occurs. It seems that the possibility of a compartment syndrome is a specific, but a rare risk of a prolonged knee-chest position. PMID- 2187163 TI - Strategy and timing of peripheral nerve surgery. AB - The authors review the latest theories of peripheral nerve regeneration and repair. They present their research on nerve regeneration including the alterations in the mother cell body, and in the distal part of the axon, and the time required to reach the best production of amino acids for cytoskeleton reconstruction. Other research of particular interest which is presented regards the chemotactic arrangement of motor and sensory axons inside a vein. This research has shown that the axons are able to find their way to the appropriate (sensory or motor) distal endoneural tubes. Adoption phenomena are also presented. The discussion of surgery includes the type (suture, glueing, grafts, tubulization) and the time of surgical repair. Timing and repair strategies are related to the site of the lesion (which can require that a greater or smaller amount of cytoskeleton be reconstructed), the type of the injury, the state of surrounding tissues, the age of the patients, injuries to muscles, tendons, bones, vessels and skin. A scheme of strategy is proposed. PMID- 2187164 TI - [Malaria and pregnancy. Theoretical premises and practical behavior]. AB - Although knowledge of mutual relations between malaria and pregnancy remain incomplete, malaria is a very real risk for both mothers and foetuses in tropical country obstetrics. On the basis of personal experience in Somalia, some theoretical premises are reported on relations between malaria and pregnancy and a consolidated therapeutic protocol is illustrated. PMID- 2187165 TI - [Antimalarial chemoprophylaxis in pregnancy]. AB - The drugs available for malaria chemoprophylaxis in pregnancy and their posology, side-effect in pregnant women and foetus are analyzed particularly for areas of high multidrug resistance. Chloroquine and proguanil are the most used with few side-effects, while pyrimethamine is recommended only for chloroquine-resistant Plasmodium falciparum spp. PMID- 2187166 TI - [Hormonal contraception using estroprogestins]. AB - Today the estroprogestagen pill is the most valid method of contraception given that its benefits far outweigh its risks. The paper stresses the importance of a thorough anamnestic, clinical and laboratory examination so as to obtain correct and safe steroid contraception. The efficacy and excellent tolerance of the combined method currently make it the most widespread form of oral contraception. PMID- 2187167 TI - [Role of Mycoplasma hominis in acute infections of the female genital system]. AB - A study was carried out on the role of mycoplasma hominis in obstetric and gynecological infections, and the paper reports a case report of acute pelvoperitonitis in a woman fitted with an IUD. The important role of early preoperative diagnosis in underlined and the current criteria for correct antibiotic therapy are discussed. PMID- 2187168 TI - [Ogilvie syndrome after cesarean section. A clinical contribution]. AB - Following the observation of a case of acute pseudo-obstruction of the colon (Ogilvie's syndrome) after cesarean section, the Authors describe their clinical experience in relation to recently published reports. While discussing other features of the syndrome, the importance of radiological monitoring of the colonic stasis and the validity of perendoscopic decompression of the colon as an efficacious therapy are underlined. PMID- 2187169 TI - [Defibrotide in the prevention of deep venous thrombosis in gynecologic surgery. A controlled study versus calcium heparin in 120 patients]. AB - The efficacy of defibrotide and calcium heparin in the prevention of Deep Vein Thrombosis (DVT) in gynecological surgery were compared in a randomized study. Seventy patients candidate to gynecological surgery (for benign conditions) and 50 candidate to surgery for malignancies were randomly allocated either to defibrotide (400 mg b.i.d. IM from the day before operation to the 7th postoperative day, n = 60) or to calcium heparin (5000 IU t.i.d. SC from the operation to the 7th postoperative day, n = 70). The diagnosis of DVT was made with impedance plethysmography and if necessary confirmed with phlebography. No patient developed established DVT in either groups and no adverse reactions were observed. These results indicate that defibrotide may be considered as an alternative to heparin in the DVT prophylaxis in gynecological surgery. PMID- 2187171 TI - Matisse. PMID- 2187170 TI - [Multicenter study in the Campania region on the clinical effectiveness and tolerance of nimesulide in gynecologic inflammatory diseases]. AB - Two-hundred and twenty patients, aged between 18 and 71 years, participated in a multicenter study in order to assay the efficacy and tolerability of nimesulide in gynecological inflammatory diseases. Forty and two patients were affected by adnexitis, 37 by cervicitis, 12 by endometritis, 9 by myometritis and 120 patients presented more pathologies associated. All the patients were treated with nimesulide 100 mg granular (sachets) b.i.d. for a mean period of 19.5 days. The treatment with nimesulide produced good results in all pathologies, significantly reducing the intensity of symptomatology. The tolerability of the drug resulted to be good. PMID- 2187172 TI - [Preservative-free timolol eye drops--surface-anesthetic effect and local compatibility]. AB - 0.5% timolol without preservative reduces corneal sensitivity for a shorter period of time than timolol with preservative. The subjective tolerance of unpreserved timolol is much better than that of preserved timolol. The latter and 0.5% levobunolol are significantly more poorly tolerated than buffer solution. The smaller the anesthetic side effects, the better the subjective tolerance of the beta-blockers. PMID- 2187173 TI - Newborn screening for cystic fibrosis is complicated by age-related decline in immunoreactive trypsinogen levels. AB - Detection of elevated levels of immunoreactive trypsinogen (IRT) in dried neonatal blood spots has been used as a screening test for cystic fibrosis. In other cystic fibrosis newborn-screening studies, a sweat chloride test is generally performed only if an infant has a persistent IRT level above a selected cutoff value on both the initial and subsequent specimens. Neither the timing of the second specimen nor the value of the cutoff point for the second specimen has been comprehensively evaluated. In this randomized, controlled study, 145,024 infants were screened in the neonatal period for cystic fibrosis using the 99.8 percentile (180 ng/mL) as the neonatal cutoff point. A total of 129 infants had elevated neonatal IRT levels and had negative results on sweat tests (false positive by IRT screening). A total of 54 children with cystic fibrosis were identified in the screened and comparison groups. Excluding patients with meconium ileus, 4 infants with cystic fibrosis had neonatal IRT values less than 180 ng/mL, and an additional 9 infants with cystic fibrosis had values decline to less than 180 ng/mL within the first 2 1/2 months of age. The IRT values of infants with and without cystic fibrosis overlapped considerably beyond 30 days of age. These findings suggest that further refinement of cystic fibrosis screening methodology will be necessary to achieve an acceptable sensitivity and specificity. PMID- 2187174 TI - Periventricular-intraventricular hemorrhage, sonographic localization, phenobarbital, and motor abnormalities in low birth weight infants. AB - A total of 228 low birth weight (less than 1750 g), mechanically ventilated infants with and without periventricular-intraventricular hemorrhage were examined at 18 months corrected age to assess the relationship between cranial ultrasonographic findings and specific motor abnormalities. All infants were previously enrolled in a double-blind, randomized, prospective clinical trial of phenobarbital prophylaxis against periventricular-intraventricular hemorrhage. Ultrasonographic abnormalities on the scans performed between 7 and 13 days of life were categorized as germinal matrix hemorrhage, lateral ventricular hemorrhage, parenchymal hemorrhage, ventriculomegaly, and any hemorrhage. Regardless of anatomical location, periventricular-intraventricular hemorrhage was associated with an increased risk for developing motor abnormalities. Hypertonia and hyperreflexia/ankle clonus were most common. No abnormal motor findings distinguished unilateral from bilateral germinal matrix hemorrhage and lateral ventricular hemorrhage or between phenobarbital and placebo treatment. None of the 5 infants with parenchymal hemorrhage had spastic cerebral palsy. Ventriculomegaly was associated with a fivefold increase in risk for spastic cerebral palsy and delayed walking and a threefold increase for hypertonia and hyperreflexia/clonus. The results suggest that ventriculomegaly, observed even as early as the first week of life, might be a significant antecedent of later motor abnormalities among the survivors of periventricular-intraventricular hemorrhage. PMID- 2187175 TI - Dose-response relationship of inhaled metaproterenol sulfate in preschool children with mild asthma. AB - The dose-response relationship of single doses of nebulized metaproterenol sulfate 5% inhalant solution was evaluated by placebo-controlled, parallel-group study of 30 children, aged 3 to 6 years old, with stable asthma. Total respiratory resistance, the primary variable used to assess response, was measured by the forced oscillation method for a period of 6 hours from the start of inhalation. When comparisons were made between metaproterenol sulfate and saline, only 0.01 and 0.02 mL/kg showed significant bronchodilation (P less than .05) in percent change from baseline and area under the curve. However, no significant differences were seen between these doses. Moreover, the effect was sustained for 3 hours with both higher doses. Minimal side effects were observed. Metaproterenol sulfate 5% inhalant solution at a dose of 0.01 mL/kg seems to be optimal to elicit significant and sustained bronchodilatory response in preschool children with mild asthma. PMID- 2187176 TI - Multicenter trial of single-dose modified bovine surfactant extract (Survanta) for prevention of respiratory distress syndrome. Ross Collaborative Surfactant Prevention Study Group. AB - A multicenter, prospective randomized controlled trial was performed comparing the efficacy of a single intratracheal dose of modified bovine surfactant extract (Survanta, 100 mg/kg, Abbott Laboratory, North Chicago, IL) with air placebo in preventing respiratory distress syndrome. Infants were enrolled if they were estimated to be between 24 and 30 weeks' gestation, weighed between 750 and 1250 g, and were intubated and stabilized within 15 minutes after birth. A total of 160 infants were treated (79 with surfactant, 81 with air placebo) between 4 and 37 minutes after birth (median time 12 minutes). Of these, 5 infants were excluded from the final analysis. The 72-hour average values for the arterial alveolar oxygen ratio, fraction of inspired oxygen, and mean airway pressure were calculated from the area under the curve of scheduled values measured throughout 72 hours. Clinical status was classified using five ordered categories (no supplemental oxygen or assisted ventilation, supplemental oxygen only, continuous positive airway pressure or assisted ventilation with intermittent mandatory ventilation less than or equal to 6 breaths/min, assisted ventilation with intermittent mandatory ventilation greater than 6 breaths/min, death). Chest radiographs at 24 hours were graded for severity of respiratory distress syndrome. Infants receiving Survanta had less severe radiographic changes at 24 hours of age and decreased average fraction of inspired oxygen (31% vs 42%, P = .002) compared with control infants. No differences were noted in the average arterial-alveolar oxygen ratio, mean airway pressure, or clinical status on days 7 and 28. A beneficial effect was noted in the incidence of pneumothorax (P = .057) and an increase was noted in the incidence of necrotizing enterocolitis (P = .052). No differences in incidence of patent ductus arteriosus, intraventricular hemorrhage, sepsis, or bronchopulmonary dysplasia were seen. According to results of a secondary analysis, there was improvement in the fraction of inspired oxygen and a greater number of survivors without bronchopulmonary dysplasia in the subgroup of infants weighing less than 1000 g who were treated with surfactant. It was concluded that a single dose of Survanta given shortly after birth resulted in decreased severity of chest radiographic findings 24 hours after treatment and improved oxygenation during 72 hours after treatment, but did not improve other acute measures of disease severity or clinical status later in the neonatal period. The group at highest risk for respiratory distress syndrome (infants with birth weights between 750 and 999 g) may benefit the most from preventive therapy. PMID- 2187177 TI - Solution conformation of several free tRNALeu species from bean, yeast and Escherichia coli and interaction of these tRNAs with bean cytoplasmic Leucyl-tRNA synthetase. A phosphate alkylation study with ethylnitrosourea. AB - The solution conformation of eight leucine tRNAs from Phaseolus vulgaris, baker's yeast and Escherichia coli, characterized by long variable regions, and the interaction of four of them with bean cytoplasmic leucyl-tRNA synthetase were studied by phosphate mapping with ethylnitrosourea. Phosphate reactivities in the variable regions agree with the existence of RNA helices closed by miniloops. At the junction of these regions with the T-stem, phosphate 48 is strongly protected, in contrast to small variable region tRNAs where P49 is protected. The constant protection of P22 is another characteristics of leucine tRNAs. Conformational differences between leucine isoacceptors concern the anticodon region, the D-arm and the variable region. In several parts of free tRNALeu species, e.g. in the T-loop, phosphate reactivities are similar to those found in tRNAs of other specificities, indicating conformational similarities among tRNAs. Phosphate alkylation of four leucine tRNAs complexed to leucyl-tRNA synthetase indicates that the 3'-side of the anticodon stem, the D-stem and the hinge region between the anticodon and D-stems are in contact with the plant enzyme. PMID- 2187178 TI - Characterisation of the DNA binding domain of the yeast RAP1 protein. AB - The 827 amino acid yeast RAP1 protein interacts with DNA to regulate gene expression at numerous unrelated loci in the yeast genome. By a combination of amino, carboxy and internal deletions, we have defined an internal 235 amino acid fragment of the yeast RAP1 protein that can bind efficiently to the RAP1 binding site of the PGK Upstream Activation Sequence (UAS). This domain spans residues 361 to 596 of the full length protein and lacks any homology to the DNA binding 'zinc finger' or 'helix-turn-helix' structural motifs. All the RAP1 binding sites we have tested bind domain 361-596, arguing that RAP1 binds all its chromosomal sites via this domain. The domain could not be further reduced in size suggesting that it represents the minimal functional DNA binding domain. The relevance of potential regions of secondary structure within the minimal binding domain is discussed. PMID- 2187180 TI - Nucleotide sequence of the cell-envelope murG gene of Escherichia coli. PMID- 2187179 TI - Yeast general transcription factor GFI: sequence requirements for binding to DNA and evolutionary conservation. AB - GFI is an abundant DNA binding protein in the yeast S. cerevisiae. The protein binds to specific sequences in both ARS elements and the upstream regions of a large number of genes and is likely to play an important role in yeast cell growth. To get insight into the relative strength of the various GFI-DNA binding sites within the yeast genome, we have determined dissociation rates for several GFI-DNA complexes and found them to vary over a 70-fold range. Strong binding sites for GFI are present in the upstream activating sequences of the gene encoding the 40 kDa subunit II of the QH2:cytochrome c reductase, the gene encoding ribosomal protein S33 and in the intron of the actin gene. The binding site in the ARS1-TRP1 region is of intermediate strength. All strong binding sites conform to the sequence 5' RTCRYYYNNNACG-3'. Modification interference experiments and studies with mutant binding sites indicate that critical bases for GFI recognition are within the two elements of the consensus DNA recognition sequence. Proteins with the DNA binding specificities of GFI and GFII can also be detected in the yeast K. lactis, suggesting evolutionary conservation of at least the respective DNA-binding domains in both yeasts. PMID- 2187181 TI - Broad host range plasmid RK2 encodes a polypeptide related to single-stranded DNA binding protein (SSB) of Escherichia coli. PMID- 2187182 TI - Nucleotide sequence of the regulatory region of the gene pbpB of Escherichia coli. PMID- 2187183 TI - The nucleotide sequence of gene rpIJ encoding ribosomal protein L10 of Salmonella typhimurium. PMID- 2187184 TI - [Determination of the arterio-portal blood flow relations of the liver--results using 99mTc-hepatobida and a review of methods]. AB - The arterial-to-portalvenous blood flow ratio (APV) has been determined routinely within liver bile studies carried out with 99mTc-hepatobida. Out of 1300 patients studied since 1978, 80 were analysed in detail concerning the fixed time parameters to separate the arterial and the portalvenous phase. The arterial phase was assumed to end 4 s after the first aortal peak, immediately followed by a portalvenous phase of 12 s duration. The "triangular area approach" of Biersack (1977) and George (1974) developed for pertechnetate and colloid, was directly applied to hepatobida. The fixed phase limits of hepatic circulation described above were compared to circulation parameters obtained from the beginning of the right ventricular recirculation and from the first decline of the spleen curve (for the end of the arterial phase), and from the second left ventricular peak (for the end of the portal phase). Our 4 s of aortal to end-arterial time agreed excellently with a corresponding control value of 4.1 s, as did the duration of the portal phase with 12 s compared to a control value of 12.1 s. An upper normal value of 45% APV was established, based upon sensitivity, specificity and a classification of hepatic curves. The "triangular area approach" appears at first to be inconsistent from a methodological point of view. We present a critical typology of assessing the APV. Basically we distinguish between strictly intravasal and all other types of tracer. The former are studied adequately by deconvolution and subsequent "real" area approaches, reflecting the full tracer passage through the liver. All not strictly intravasal tracers (pertechnetate, colloid, hepatobida) are subjected to a model assumption of a pure uptake without relevant tracer elimination during the first pass. We conclude that the Biersack George method may be regarded as a heuristic correction of an amplitude approach within our typology, and that our fixed phase limits are justified by circulation analysis. PMID- 2187185 TI - PET and SPECT to achieve diagnostic impact. PMID- 2187186 TI - Tissue-specific expression of silkmoth chorion genes in vivo using Bombyx mori nuclear polyhedrosis virus as a transducing vector. AB - A pair of silkmoth chorion chromosomal genes, HcA.12-HcB.12, was inserted into a baculovirus transfer vector, pBmp2, derived from the nuclear polyhedrosis virus of Bombyx mori. This vector, which permits the insertion of foreign genetic material in the vicinity of a mutationally inactivated polyhedrin gene, was used to acquire the corresponding recombinant virus. Injection of mutant silkmoth pupae that lack all Hc chorion genes with the recombinant virus resulted in the infection of all internal organs including follicular tissue. Analysis of RNA from infected tissues has demonstrated that the two chorion genes present in the viral genome are correctly transcribed under the control of their own promoter in follicular cells, the tissue in which chorion genes are normally expressed. The chorion primary transcripts are also correctly processed in the infected follicular cells and yield mature mRNAs indistinguishable from authentic chorion mRNAs present in wild-type follicles. These results demonstrate that recombinant nuclear polyhedrosis viruses can be used as transducing vectors for introducing genetic material of host origin into the cells of the organism and that the transduced genes are transiently expressed in a tissue-specific manner under the control of their resident regulatory sequences. Thus we show the in vivo expression of cloned genes under cellular promoter control in an insect other than Drosophila melanogaster. The approach should be applicable to all insect systems that are subject to nuclear polyhedrosis virus infection. PMID- 2187187 TI - Existence of two forms of rat liver arginyl-tRNA synthetase suggests channeling of aminoacyl-tRNA for protein synthesis. AB - Arginyl-tRNA synthetase (arginine-tRNA ligase, EC 6.1.1.19) is found in extracts of mammalian cells both as a free protein (Mr = 60,000) and as a component (Mr approximately 72,000) of the high molecular weight aminoacyl-tRNA synthetase complex (Mr greater than 10(6). Several pieces of evidence indicate that the low molecular weight free form is not a proteolytic degradation product of the complex-bound enzyme but that it preexists in vivo: (i) the endogenous free form differs in size from the active proteolytic fragment generated in vitro, (ii) conditions expected to increase or decrease the amount of proteolysis do not alter the ratio of the two forms of the enzyme, and (iii) the free form contains an NH2-terminal methionine residue. A model is presented that provides a rationale for the existence of two forms of arginyl-tRNA synthetase in cells. In this model the complexed enzyme supplies arginyl-tRNA for protein synthesis, whereas the free enzyme provides arginyl-tRNA for the NH2-terminal arginine modification of proteins by arginyl-tRNA:protein arginyltransferase. This latter process targets certain proteins for removal by the ubiquitin-dependent protein degradation pathway. The necessity for an additional pool of arginyl-tRNA for the modification reaction leads to the conclusion that the arginyl-tRNA destined for protein synthesis (and/or protein modification) is channeled and unavailable for other processes. Other evidence supporting channeling in protein synthesis is discussed. PMID- 2187188 TI - Transfection of beta-casein chimeric gene and hormonal induction of its expression in primary murine mammary epithelial cells. AB - To study the regulatory sequence elements responsible for casein gene expression, we constructed a chimeric gene containing 5.3 kilobases (kb) of the 5'-flanking sequence and 1.6 kb of the 3'-flanking sequence of the mouse beta-casein gene fused to the bacterial chloramphenicol acetyl-transferase (CAT) gene. The chimeric gene was transfected by the calcium phosphate-precipitation procedure into primary mouse mammary epithelial cells prepared from pregnant mice. The transfection procedure had negligible effect on expression of the endogenous beta casein gene. Expression of the beta-casein-CAT chimeric gene required the synergistic actions of insulin, hydrocortisone, and prolactin. Expression of the chimeric gene also depended on the appropriate substratum because the degree of hormonal induction of the chimeric gene was much higher in cells cultured on a reconstituted basement membrane (Matrigel) than in cells cultured on either type I collagen gel or plastic. On the other hand, the expression of a simian virus 40 CAT chimeric gene in which the CAT gene was driven by the early promoter of the virus was not influenced by the hormonal milieu and occurred at the highest level in cells cultured on plastic. Additional transfection experiments with a series of beta-casein-CAT constructs suggested the existence of regulatory elements responsible for hormonal induction and negative regulatory elements. PMID- 2187189 TI - Repopulation of the atrophied thymus in diabetic rats by insulin-like growth factor I. AB - Atrophy of the thymus is one of the consequences of severe insulin deficiency. We describe here that the weight and the architecture of the thymus of diabetic rats is restored towards normal not only by insulin but also by insulin-like growth factor I (IGF-I) treatment. In contrast to insulin, this effect of IGF-I occurs despite persisting hyperglycemia and adrenal hyperplasia. We also investigated the in vivo effect of IGF-I on replication and differentiation of thymocytes from streptozotocin-induced diabetic rats. Thymocytes from diabetic rats incorporated less [3H]thymidine than did thymocytes from healthy rats. Insulin, as well as IGF I treatment of diabetic rats increased [3H]thymidine incorporation by thymocytes. Flow cytometry of thymocytes labeled with monoclonal antibodies revealed a decreased expression of the Thy-1 antigen in diabetic rats compared with control rats. In addition, a major deficiency of thymocytes expressing simultaneously the W3/25 and the Ox8 antigens (corresponding to immature human CD4+/CD8+ thymocytes) was observed. These changes were restored towards normal by insulin as well as by IGF-I treatment. The antibody response to a T cell-dependent antigen (bovine serum albumin) was comparable in normal and diabetic rats. We conclude that IGF-I has important effects on the thymocyte number and the presence of CD4+/CD8+ immature cells in the thymus of diabetic rats despite persisting hyperglycemia. However, helper T-cell function for antibody production appears to be preserved even in the severely diabetic state. PMID- 2187190 TI - The gamma subunit of DNA polymerase III holoenzyme of Escherichia coli is produced by ribosomal frameshifting. AB - The tau and gamma subunits of DNA polymerase III holoenzyme are both products of the dnaX gene. Since tau and gamma are required as stoichiometric components of the replicative complex, a mechanism must exist for the cell to coordinate their synthesis and ensure that both subunits are present in an adequate quantity and ratio for assembly. We have proposed that gamma is produced by a translational frameshift event. In this report, we describe the use of dnaX-lacZ fusions in all three reading frames to demonstrate that gamma, the shorter product of dnaX, is generated by ribosomal frameshifting to the -1 reading frame of the mRNA within an oligo(A) sequence that is followed by a sequence predicted to form a stable secondary structure. Immediately after frameshifting a stop codon is encountered, leading to translational termination. Mutagenesis of the oligo(A) sequence abolishes frameshifting, and partial disruption of the predicted distal secondary structure severely impairs the efficiency. Comparison of the expression of lacZ fused to dnaX distal to the site of frameshifting in the -1 and 0 reading frames indicates that the efficiency of frameshifting is approximately 40%. PMID- 2187191 TI - Reciprocal expression of human ETS1 and ETS2 genes during T-cell activation: regulatory role for the protooncogene ETS1. AB - The expression of the protooncogenes ETS1 and ETS2 has been studied in purified human T cells activated either by cross-linking of the T-cell receptor-CD3 complex on their cell surface or by direct stimulation with phorbol esters and ionomycin. Our results show that resting T cells express high levels of ETS1 mRNA and protein, while expression of ETS2 is undetectable. Upon T-cell activation, ETS2 mRNA and proteins are induced, while ETS1 gene expression decreases to very low levels. Late after stimulation, ETS1 mRNA is reinduced and maintained at a high level, while ETS2 gene expression decreases to undetectable levels. Therefore, it appears that in human T cells, ETS2 gene products are associated with cellular activation and proliferation, while ETS1 gene products are preferentially expressed in a quiescent state. PMID- 2187192 TI - Transforming growth factor beta 1 suppression of c-myc gene transcription: role in inhibition of keratinocyte proliferation. AB - Transforming growth factor beta 1 (TGF-beta 1) is a potent growth inhibitor for many cell types, including most epithelial cells. However, the mechanism of growth inhibition is unknown. In skin keratinocytes, TGF-beta 1 has been shown to inhibit growth and to rapidly reduce c-myc expression. It has been demonstrated that protein synthesis is required for TGF-beta 1 regulation of c-myc in keratinocytes. Here we present evidence that treatment of mouse BALB/MK keratinocyte cells with either antisense c-myc oligonucleotides or TGF-beta 1 inhibited cell entry into S phase. These results suggest that TGF-beta inhibition of c-myc expression may be essential for growth inhibition by TGF-beta 1. The block in c-myc expression by TGF-beta 1 occurred at the level of transcriptional initiation. Studies with a series of 5' deletion c-myc/chloramphenicol acetyltransferase constructs indicated that a cis regulatory element(s), which resides between positions -100 and +71 relative to P1 transcription start site, is responsible for the TGF-beta 1 responsiveness. Based on these data, it is proposed that the mechanism of TGF-beta 1 growth inhibition involves synthesis or modification of a protein that may interact with a specific element(s) in the 5' regulatory region of the c-myc gene, resulting in inhibition of transcriptional initiation. PMID- 2187193 TI - Human mast cell tryptase: multiple cDNAs and genes reveal a multigene serine protease family. AB - Three different cDNAs and a gene encoding human skin mast cell tryptase have been cloned and sequenced in their entirety. The deduced amino acid sequences reveal a 30-amino acid prepropeptide followed by a 245-amino acid catalytic domain. The C terminal undecapeptide of the human preprosequence is identical in dog tryptase and appears to be part of a prosequence unique among serine proteases. The differences among the three human tryptase catalytic domains include the loss of a consensus N-glycosylation site in one cDNA, which may explain some of the heterogeneity in size and susceptibility to deglycosylation seen in tryptase preparations. All three tryptase cDNAs are distinct from a recently reported cDNA obtained from a human lung mast cell library. A skin tryptase cDNA was used to isolate a human tryptase gene, the exons of which match one of the skin-derived cDNAs. The organization of the approximately 1.8-kilobase-pair tryptase gene is unique and is not closely related to that of any other mast cell or leukocyte serine protease. The 5' regulatory regions of the gene share features with those of other serine proteases, including mast cell chymase, but are unusual in being separated from the protein-coding sequence by an intron. High-stringency hybridization of a human genomic DNA blot with a fragment of the tryptase gene confirms the presence of multiple tryptase genes. These findings provide genetic evidence that human mast cell tryptases are the products of a multigene family. PMID- 2187194 TI - Ultrasensitivity and heavy-metal selectivity of the allosterically modulated MerR transcription complex. AB - The MerR metalloregulatory protein is a heavy-metal receptor that functions as the repressor and Hg(II)-responsive transcription activator of the prokaryotic mercury-resistance (mer) genes. We demonstrate that this allosterically modulated regulatory protein is sensitive to HgCl2 concentrations of 1.0 +/- 0.3 x 10(-8) M in the presence of 1.0 x 10(-3) M dithiothreitol for half-maximal induction of transcription of the mer promoter by Escherichia coli RNA polymerase in vitro. Transcription mediated by MerR increases from 10% to 90% of maximum in response to a 7-fold change in concentration of HgCl2, consistent with a threshold phenomenon known as ultrasensitivity. In addition, MerR exhibits a high degree of selectivity. Cd(II), Zn(II), Ag(I), Au(I), and Au(III) have been found to partially stimulate transcription in the presence of MerR, but concentrations at least two to three orders of magnitude greater than for Hg(II) are required. The molecular basis of the ultrasensitivity and selectivity phenomena are postulated to arise from the unusual topology of the transcription complex and a rare trigonal mercuric ion coordination environment, respectively. This mercuric ion induced switch is to our knowledge the only known example of ultrasensitivity in a signal-responsive transcription mechanism. PMID- 2187195 TI - Human immunodeficiency virus causes mononuclear phagocyte dysfunction. AB - There is compelling clinical evidence for dysfunction of the mononuclear phagocyte system in patients with AIDS, which is believed due in part to loss of T-cell cooperativity. The direct consequences of human immunodeficiency virus infection on macrophage function are unknown. To address this question we infected normal human macrophages in vitro with a monocytotropic strain of human immunodeficiency virus and performed assays to quantify their extra- and intracellular killing ability. Human immunodeficiency virus-infected macrophages were significantly less effective than control cells in mediating antibody dependent cell-mediated cytotoxicity against leukemic cell targets and intracellular killing of Candida pseudotropicalis. The functional defects were profound, related temporarily to active virus production by the macrophages, and could not be overcome by granulocyte-macrophage colony-stimulating factor. Treatment of macrophages with 3'-azido-3'-deoxythymidine (AZT) 6 days after infection caused a marked decrease in virus production and prevented development of the intracellular killing functional defect. The results suggest that early antiviral therapy may be useful in preventing or mitigating some virus-induced mononuclear phagocyte dysfunction. PMID- 2187196 TI - Asymmetric distribution of dystrophin in developing and adult Torpedo marmorata electrocyte: evidence for its association with the acetylcholine receptor-rich membrane. AB - Dystrophin has been shown to occur in Torpedo electrocyte [Chang, H. W., Bock, E. & Bonilla, E. (1989) J. Biol. Chem. 264, 20831-20834], a highly polarized syncytium that is embryologically derived from skeletal muscle and displays functionally distinct plasma membrane domains on its innervated and noninnervated faces. In the present study, we investigated the subcellular distribution of dystrophin in the adult electrocyte from Torpedo marmorata and the evolution of its distribution during embryogenesis. Immunofluorescence experiments performed on adult electrocytes with a polyclonal antibody directed against chicken dystrophin revealed that dystrophin immunoreactivity codistributed exclusively with the acetylcholine receptor along the innervated membrane. At the ultrastructural level, dystrophin immunoreactivity appears confined to the face of the subsynaptic membrane exposed to the cytoplasm. In developing electrocytes (45-mm embryo), dystrophin is already detectable at the acetylcholine receptor rich ventral pole of the cells before the entry of the electromotor axons. Furthermore, we show that dystrophin represents a major component of purified membrane fractions rich in acetylcholine receptor. A putative role of dystrophin in the organization and stabilization of the subsynaptic membrane domain of the electrocyte is discussed. PMID- 2187197 TI - Escherichia coli thymidylate synthase: amino acid substitutions by suppression of amber nonsense mutations. AB - By using site-directed oligonucleotide mutagenesis, amber nonsense stop codons (5'-TAG-3') have been introduced at 20 sites in the Escherichia coli thymidylate synthase gene. By transforming the thyA mutant plasmids into 13 strains, each of which harbor different amber suppressor tRNAs, we were able to generate over 245 amino acid substitutions in E. coli thymidylate synthase (EC 2.1.1.45). Growth characteristics of these mutants have been studied, yielding a body of information that includes some surprising results in light of the recently published crystal structure of the enzyme. PMID- 2187198 TI - Reactivity of primary biliary cirrhosis sera with Escherichia coli dihydrolipoamide acetyltransferase (E2p): characterization of the main immunogenic region. AB - Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in the serum. The major antigens recognized by the antibodies are the E2 components of the 2 oxo acid dehydrogenase complexes, all of which possess covalently attached lipoic acid cofactors. A bacterial etiology has been proposed for the disease, and patients' antibodies are known to recognize the E2 subunits (E2p) of both mammalian and bacterial pyruvate dehydrogenase complexes. Immunoblotting and ELISA inhibition techniques using extracts of Escherichia coli deletion strains, genetically restructured E2 polypeptides, and isolated lipoyl domains demonstrate that (i) the E2o subunit of the E. coli 2-oxoglutarate dehydrogenase complex is recognized by patients' antibodies; (ii) the main immunogenic region of E2p lies within the lipoly domains; (iii) the presence of a lipoly residue within the domain is crucial for effective recognition by the antibodies; and (iv) octanoylated E2p, octanoylated E2o, and octanoylated lipoyl domain, produced by a mutant deficient in lipoate biosynthesis, are recognized by patients' antibodies but not as effectively as their lipoylated counterparts. These findings indicate that antibodies in PBC patients' sera bind to a unique peptide-cofactor conformation within the lipoyl domains of the E2 polypeptides and that this epitope is partially mimicked by substituting the lipoyl cofactor with an octanoyl group. PMID- 2187201 TI - The role of prostaglandins in human parturition. PMID- 2187199 TI - Human immunodeficiency virus type 1 expression in the central nervous system correlates directly with extent of disease. AB - To investigate human immunodeficiency virus type 1 (HIV-1) pathogenesis in infected individuals and examine the correlation of HIV-1 expression with extent of clinical and pathologic disease, we studied spinal cords from acquired immunodeficiency syndrome patients with a wide range of spinal cord pathology. By performing in situ hybridization with HIV-1-specific riboprobes, we detected HIV 1 RNA in all 10 cords from acquired immunodeficiency syndrome patients with a common, characteristic pathologic entity called vacuolar myelopathy but not in 10 control cords from HIV-1-infected and uninfected patients. In the cords from individuals with vacuolar myelopathy, the level of HIV-1 RNA expression correlated directly with extent of spinal cord pathology and clinical findings. These data support a role for HIV-1 in the pathogenesis of tissue damage and related clinical disease in infected individuals. PMID- 2187202 TI - Prostaglandin deficiency. AB - Healthy cells from virtually all tissues synthesize a variety of prostaglandins, autacoids which can significantly alter cellular functions. An absolute or relative deficiency of prostaglandins has now been demonstrated in many diseases or clinical conditions. These include 'natural' disorders such as peptic ulcer disease and diabetes mellitus. These also include 'acquired' or iatrogenic conditions such as cyclosporine nephrotoxicity and the gastropathy induced by nonsteroidal anti-inflammatory drugs. We believe that the diversity of the disorders associated with prostaglandin deficiency may be wider and of greater pathogenetic importance than is currently recognized. We propose: 1) that prostaglandin deficiency will be demonstrated in many abnormalities which are now described as of uncertain etiology; and 2) that adverse effects from many commonly prescribed drugs may also be related to an unrecognized and unfavorable alteration in prostaglandin synthesis, disposal, or activity. PMID- 2187200 TI - Immunization of Aotus monkeys with Plasmodium falciparum blood-stage recombinant proteins. AB - The current spread of multidrug-resistant malaria demands rapid vaccine development against the major pathogen Plasmodium falciparum. The high quantities of protein required for a worldwide vaccination campaign select recombinant DNA technology as a practical approach for large-scale antigen production. We describe the vaccination of Aotus monkeys with two recombinant blood-stage antigens (recombinant p41 and 190N) that were considered as vaccine candidates because parasite-derived antigen preparations could protect susceptible monkeys from an otherwise lethal malaria infection. In contrast to the natural antigen, recombinant p41 protein (P. falciparum aldolase) could not protect monkeys, although all animals seroconverted. 190N antigen, a recombinant protein containing conserved sequences of the major merozoite surface antigen p190, protected two of five monkeys from critical levels of infection with the highly virulent FVO isolate of P. falciparum. However, the B- and T-cell responses to 190N antigen were similar in protected and unprotected animals so that other unknown factors may contribute to protection. Higher purity or lack of protective epitopes or different structure of protective epitopes in the recombinant proteins might explain the better performance of parasite-derived antigens in vaccination trials. The partial protection obtained with 190N antigen suggests that this molecule could contribute to a vaccine mixture against P. falciparum. PMID- 2187203 TI - [The participation of German pharmacists in the chemical revolution at the turn of the 18th to the 19th century]. AB - Between 1775 and about 1800 the Phlogiston theory was replaced by the Oxygen theory. Both systems are presented briefly. Pharmacists on both sides were involved in the scientific discussions of the Chemical Revolution in Germany. Their contribution is appreciated. Finally the peculiarities of this paradigm exchange are described. PMID- 2187204 TI - [Herman Hager (1816-1897)--the heights and depths of his life]. AB - The "Hager", undoubtedly a practical, indispensable encyclopedia of more than 10,000 pages is to be found in every German pharmacy. The changeable life of his author, Hans Hermann Julius Hager, who was born in Berlin, is reflected in a contradictory way in pharmaceutical history. Although he never completed a study he reached the highest degree of pharmaceutical science as a genuine autodidact but was neglected and insulted during life time. He died in very poor circumstances at Neuruppin, where he had come to live at his son's place one year before his death. PMID- 2187205 TI - [Otto Unverdorben--a successful scientist from Niederlausitz]. PMID- 2187206 TI - [The biochemical basis of pharmaceutical chemistry. 6. Intracellular acting hormones]. PMID- 2187207 TI - [Effervescent tablets--a nearly forgotten drug form]. PMID- 2187208 TI - Dangerous medicine: horror stories from fiction. PMID- 2187210 TI - Studying the person in the patient: a look back at developments. PMID- 2187209 TI - Rudolph Fisher: Harlem renaissance physician-writer. PMID- 2187211 TI - Recurrent brief depression. A new concept of depression. AB - In an epidemiological cohort study from age 20 to 28, DSM-III criteria were used for the diagnosis of Major Depressive Disorder (MDD). Many subjects met the criteria A (dysphoric mood or loss of interest or pleasure) and B (presence of at least four out of eight criteria) but the episodes were shorter than the minimum of two weeks. Within this group of Brief Depressive Episodes, a recurrent form can be characterized with at least monthly reoccurrence over one year. These subjects are defined as cases of Recurrent Brief Depression (RBD) if they also suffer from reduced capacity at work. No exclusion criteria are applied. In the present cohort, the prevalence and treatment rates of RBD are comparable to MDD. PMID- 2187212 TI - Hypothesis: involvement of the serotonergic system in the clinical expression of monosymptomatic hypochondriasis. AB - Monosymptomatic hypochondriasis, including delusional parasitosis and non neurotic dysmorphophobia, are disorders which have been observed and recorded over the past century. These disorders occur commonly, and can be associated with significant morbidity. Once ominous of an extremely poor prognosis, there now exists a significant literature to suggest efficacy for pimozide. Taking LSD as a model for 5-HT2 agonist mediated hallucinogenesis, it is possible to draw comparisons to the clinical picture associated with MHP and to identify potent 5 HT2 antagonism as a shared and perhaps requisite criterion for the successful pharmacologic treatment of this disorder. Additional studies are suggested which would add to the understanding of the pathophysiology of MHP. PMID- 2187213 TI - Lorazepam vs. alprazolam in the treatment of panic disorder. AB - Sixty-seven patients with panic disorder were treated with single-blind placebo for one week before being randomized to 6 weeks of double-blind treatment with either lorazepam or alprazolam. Both drugs showed significant and comparable antipanic efficacy throughout the course of the study. With the exception of sedative effects, both drugs were well-tolerated at a mean daily dose of 7 mg for lorazepam and 3 mg for alprazolam. Lorazepam appeared to be as effective as alprazolam in the acute treatment of panic disorder. PMID- 2187214 TI - Methodological guidelines for impedance cardiography. AB - Impedance cardiography was introduced over 20 years ago as a noninvasive and unobtrusive technique for measuring systolic time intervals and cardiac output. Although our understanding of the physiological events reflected in the impedance cardiogram has become more refined, the technique's theoretical basis remains somewhat controversial and acceptance of its validity has relied heavily upon empirical validation. Largely as a consequence of this status, there have been inadequate grounds on which to develop sound methodological standardization. Currently, the methodological approaches that have been most frequently adopted may be viewed as representing the standard. The various aspects of impedance methodology are discussed, and alternative approaches described, with the objective of providing an informed basis for choosing among these methodological alternatives. It is recommended that studies utilizing impedance cardiography should be reported with clear and detailed methodological description. This should help clarify the extent to which methodological differences may underlie any discrepant research observations, as well as facilitate the emergence of improved methodological standards. PMID- 2187215 TI - Auger electron emitters: insights gained from in vitro experiments. AB - This paper outlines the evolution of the current rationale for research into the biological effects of tissue-incorporated Auger electron emitters. The first section is a brief review of the research conducted by several groups in the last fifteen years. The second section describes the in vitro model used in our studies, dosimetric calculations, experimental techniques and recent findings. The third section focuses on the use of Auger electron emitters as in vitro microprobes for the investigation of the radiosensitivity of distinct subcellular components. Examination of the biological effects of the Auger electron emitter 125I located in different cellular compartments of a single cell line (V 79 hamster lung fibroblast) verifies that DNA is the critical cell structure for radiation damage and that the sensitive sites are of nanometer dimensions. The data from incorporation of several Auger electron emitters at the same location within DNA suggest that there are no saturation effects from the decay of these isotopes (i.e. all the emitted energy is biologically effective) and provide some insight into which of the numerous physical mechanisms accompanying the Auger decay are most important in causing cell damage. Finally the implications of Auger electron emission for radiotherapy and radiation protection in diagnostic nuclear medicine are detailed and further research possibilities are suggested. PMID- 2187216 TI - [Acute kidney failure]. PMID- 2187217 TI - [Anesthesiologic implications of human immunodeficiency virus (HIV) infection]. PMID- 2187218 TI - [Regulation of erythropoiesis: recent progress and current uncertainties]. AB - Rapid progress has occurred recently in characterizing the molecular structure of the glycoproteins controlling the growth, maturation and functional activities of hematopoietic cells. Several of these factors have been purified and cDNAs have been cloned, providing them in sufficient quantities for study and eventual clinical use. Both availability of these molecules and in vitro colony assays have revealed a large number of effects on erythroid differentiation. But, except erythropoietin (EPO), the physiological role of these hormones and their relative contributions to normal erythropoiesis remain to be specified. This paper attempts to review the most important data on this topic in 1990. PMID- 2187220 TI - [Prevention of false results in tests for occult blood in feces]. AB - The HaemoQuant test and the immunological tests are not devoid of problems so that the (pseudo)peroxidase-sensitive tests are anything but obsolete. Most of the tests are nowadays sold with reduced sensitivity, with the risk of false negative results. Nevertheless, they can yield false-positive results without a strict dairy-and-vegetable diet in which all components have undergone a heat inactivation (cooking, baking, pasteurization). Uncooked wheat bran reacts strongly, but even liberal use of cooked bran never produced a positive reaction with the sensitive 'Occultest'. Even if thoroughly cooked, all meat, except that of fish with white meat, can elicit a positive reaction. Most leaflets of commercial tests should be thoroughly revised. Also a misleading presentation of a positive reaction can be a source of errors. PMID- 2187219 TI - [Amiodarone and thyroid: the Janus effect]. AB - Iodide released from Amiodarone during a chronic treatment is 100 x higher than food iodide intake. Thyroid adaptation allows normal function but over-adaptation leads to hypothyroidism and hypo-adaptation to thyrotoxicosis. Thyrotoxicosis may also result from follicular disruption. Amiodarone inhibits 5' deiodinase type I and II and hence increases serum T4 and (transiently) TSH and decreases serum T3 concentrations. Perchlorate and corticoids may be useful in the treatment of thyrotoxicosis. PMID- 2187221 TI - [Opportunistic infections in HIV-infected patients]. AB - HIV-infected patients are prone to frequent opportunistic infections (OI). Their fundamental differences to infections in the immunocompetent host are explained. The most frequent OI is pneumonia caused by pneumocystis carinii. A brief overview on diagnostic and therapeutic aspects of encephalitis due to toxoplasma gondii, candidiasis, meningitis due to cryptococcus neoformans, tuberculosis, infection by atypical mycobacteria, infection by viruses of the herpes group--in particular cytomegalovirus--and cryptosporidiosis is given. PMID- 2187223 TI - New macrofilaricidal leads from plants? AB - The continuing need for a new safe and effective macrofilaricidal drug for the treatment of filarial infections in man is outlined, together with the possibility that structural leads for the identification and synthesis of such drugs might be derived from higher plants. Many of todays successful drugs were derived from plants and it is interesting to note that the majority were discovered through follow-up research on the folk or ethnomedical uses of plants. In this review an attempt has been made to compile a list of those plant species for which there is evidence supporting their usefulness in the treatment of filarial conditions in endemic areas. Perhaps surprisingly the use of such plant medicines appears quite widespread, and details of 90 plant species are summarised. The value of this information is discussed in the light of the fact that few of these citations are supported by clinical or scientific investigations into their efficacy, and the lack of knowledge regarding the antifilarial active constituents. It is concluded that in view of apparent failure of more rational approaches to yield macrofilaricidal leads there is justification for examining further medicinal plants, and that the data summarised might be a useful starting point for such a screening programme. PMID- 2187222 TI - [Nervous system pathology in AIDS: results of a collaborative autopsy study from Switzerland]. AB - Neuropathological lesions were studied in a consecutive autopsy series of 206 cases, comprising 61% of all patients who died of Aids in Switzerland between April 1981 and December 1988. Central nervous system involvement was found in 84% of the patients, and 17% showed multiple concomitant intracerebral lesions. Among the non-viral opportunistic infections, cerebral toxoplasmosis was most frequent (24%), whilst among the viral opportunistic infections, cytomegalovirus (CMV) encephalitis was most frequent (7%). A nodular encephalitis consisting of disseminated microglial nodules without morphological or immunocytochemical evidence of CMV occurred in 13.5% of the patients. The majority of these cases showed evidence of extracerebral CMV infection. Progressive multifocal leukoencephalopathy (PML) was observed in 6% of the patients and was associated with widespread tissue destruction and cyst formation. HIV encephalopathy occurred in 38 patients (18%) and showed two characteristic morphological patterns: progressive diffuse leukoencephalopathy (PDL) and multifocal giant cell encephalitis (MGCE). PDL was observed in 22 patients and was characterized by a diffuse demyelination and gliosis of the white matter with little inflammatory infiltrates and scattered multinucleated giant cells which were immunoreactive to HIV antigens. MGCE was found in 16 patients and was characterized by clusters of macrophages, lymphocytes, and HIV-immunoreactive multi-nucleated giant cells. In our view, PDL and MGCE represent two opposite variants of HIV-induced encephalopathies with numerous intermediate manifestations. PMID- 2187224 TI - The anthropometric status of children in Kurunegala district in Sri Lanka: its relation to water supply, sanitation and hygiene practice. AB - Anthropometric data for 1295 children were collected during cross-sectional surveys conducted in Kurunegala District, Sri Lanka between March 1987 and March 1988. The relationship between anthropometric status and a range of water, sanitation and hygiene-related exposures was examined. After taking account of socioeconomic and other potential confounding factors, some evidence was found that boiling of water was associated with improved height-for-age. It seems unlikely that boiling of water alone could be responsible for the observed increase in height-for-age. Boiling of water may be acting as a "marker" for a range of hygiene and child-care behaviours. No convincing evidence of any other association was found. In particular, water source was not associated with anthropometric status. A concurrent study conducted in the same population found evidence of a substantial reduction in diarrhoea morbidity associated with the use of improved sources. These findings, taken together, lend support to the hypothesis that interventions for the control of diarrhoea may have no detectable impact on anthropometric status. PMID- 2187225 TI - Microbiological agents associated with childhood diarrhoea in the dry zone of Sri Lanka. AB - Between March and July, 1987, faecal specimens from 371 diarrhoeal children reporting to four hospitals in the district of Kurunegala, Sri Lanka and from 121 controls with other diseases were investigated for enteric pathogens. All specimens were tested for Shigella spp, Salmonella spp and enteropathogenic Escherichia coli (EPEC). In addition, parasitic pathogens, heat labile enterotoxigenic Escherichia coli (ETEC LT), Campylobacter and rotavirus were sought among subsamples of the cases and controls. One or more pathogens were detected in the faecal specimens of 53.7% of the diarrhoeal children and 19.6% of the controls (P less than 0.001). Rotavirus was the most frequently identified pathogen. Cases (21.9%) were more likely to be positive for rotavirus than controls (6.5%) (p less than 0.05). Among children with diarrhoea the peak prevalence of rotavirus occurred in the 6-11 months age group. Shigella spp were the second most frequently isolated pathogens and the single most common cause of diarrhoea in children over two years of age. Again, cases (16.4%) were more likely to be infected than controls (1.7%) (p less than 0.001). Salmonella spp were isolated from 7.5% of diarrhoeal children and 3.3% of the controls (p greater than 0.10). Other pathogens had prevalence rates of less than 5%. Vomiting was associated with rotavirus diarrhoea (p less than 0.001), and fever with shigellosis (p = 0.02). In view of the different transmission routes and characteristics of the most important pathogens detected in this study it appears unlikely that a single environmental intervention can solve the public health problem posed by diarrhoeal diseases in Sri Lanka. PMID- 2187226 TI - Use of monoclonal antibodies for the characterization of Onchocerca volvulus antigens. AB - In order to identify Onchocerca volvulus antigens that could be considered as either diagnostic and/or immunoprophylactic, mouse monoclonal antibodies were produced against O. volvulus soluble antigens. Three were selected on the basis of their staining patterns in an indirect fluorescent antibody assay carried out on cryosections of adult O. volvulus. The first monoclonal antibody (K1-159) recognized a cuticular antigen which appeared in IFA to be restricted to the genus Onchocerca. However, neither Western blotting, nor the immunoprecipitation experiments performed on radiolabelled O. volvulus soluble antigen allowed detection of the corresponding antigen(s). The second monoclonal antibody (K1 126) bound to the muscle cells of adults. A 30,000 Mr antigen was detected by Western blot analysis of adult O. volvulus homogenate. This antigen was also recognised by sera from infected patients and corresponding antigenic determinants were detected in extracts of O. gutturosa, Acanthocheilonema viteae and Ascaris suum, but not in Brugia malayi. The third monoclonal antibody (K1 143) recognized egg shells and the surface of adult worms. The target epitope was not species specific and could be found in O. gutturosa, A. viteae, B. malayi and A. suum. The electrophoretic analysis of I-125 labelled soluble antigens and radiolabelled surface antigens of adult O. volvulus, showed numerous antigens (molecular weights ranging from 30,000 to 120,000 Mr) precipitated by K1-143. In an inhibition radioimmunoassay, K1-143 allowed the detection of corresponding antibodies in 79% of the O. volvulus patient sera tested. PMID- 2187227 TI - Detection with a monoclonal antibody of a polysaccharide antigen, excreted in the urine, in the schistosomiasis intercalatum focus of Edea (Cameroon). AB - The detection in the urine specimens of a sample of the inhabitants of Edea of a polysaccharide antigen characteristic for the genus Schistosoma, with monoclonal antibody by means of the inhibition of a passive haemagglutination test, shows that this technique is very sensitive for measuring prevalence of schistosomiasis due to S. intercalatum. In Edea, looking for eggs in stool specimens gives a low prevalence rate of the disease because of the low parasitic load. The prevalence by age, according to the voiding of eggs, is evoluting parallel to the excretion of the antigen. PMID- 2187228 TI - Evaluation of in vitro released Wuchereria bancrofti third stage larval antigens for detection of Bancroftian filariasis. AB - Three types of in vitro released excretory, secretory and metabolic antigens of Wuchereria bancrofti third larval stage (L3ESM) are evaluated in ELISA test to detect infected individuals in the endemic area. A total of 104 reference sera are used to predict the sensitivity of these antigens. None of L3 ESM antigens, although homologous in nature, did not identify correctly the categorised reference sera. This study clearly indicated a need for defined antigens to detect W. bancrofti infection early in the endemic residents. PMID- 2187229 TI - Childhood diarrhoea in Sri Lanka: a case-control study of the impact of improved water sources. AB - Between January 1987 and March 1988 a case-control study of the impact of improved water sources on childhood diarrhoea was conducted in Kurunegala District, Sri Lanka. Two thousand four hundred and fifty eight cases of diarrhoea were recruited at five of the hospitals in the district. Another 4140 children presenting at the same hospitals with complaints other than diarrhoea were recruited as controls. Data from the five hospitals suggest that children in households drawing their drinking water from handpumps suffer 46% fewer episodes of diarrhoea than children in families using unprotected traditional sources (95% c. i. 29-59%), while children in families using protected traditional wells suffer 35% fewer episodes than children in families using unprotected traditional sources (95% c. i. 27-41%). There were, however, substantial differences between the different hospitals. Among children recruited at one of the hospitals, the reduction in diarrhoea rates associated with the use of improved sources was estimated to be 93% compared with an average of 18% for the other four hospitals. In common with other case-control studies conducted in Malawi and the Philippines, little evidence of confounding of the association between diarrhoea and water supply was observed. Our results suggest that, in Sri Lanka, the use of improved water supplies, including protected traditional wells, rather than unprotected traditional sources may lead to a substantial reduction in diarrhoea morbidity among children under five years of age. PMID- 2187230 TI - [Undesirable side effects of contrast media during i.v. DSA--a comparison of 2 nonionic contrast media]. AB - For the first time a controlled double-blind study was performed to compare side effects and complications of i.v. DSA with central venous application of iopamidol and iopromide. 200 consecutive patients 15-85 years of age were studied. The randomisation brought up two homogeneously structured groups of 100 patients each. Using a given protocol, 66% of the patients were classified as high-risk patients. Side-effects and complications were registered by an extensive, standardised protocol. In 71 (35.5%) of 200 patients contrast-media related side effects and complications were noted. 37 reactions in 24 patients (9 iopamidol, 15 iopromide group) were classified as clinically relevant. In four patients (4%) of each group a drug therapy was initiated. Contrast-media related reactions occurred with delay in 5.5% of initially symptom-free patients. In no case intensive care or hospital admission became necessary. There were no significant differences between the two non-ionic contrast media in the incidence of side effects and complications. Both substances were well tolerated in i.v. DSA. In the total population patients with diseases known as auto-immune diseases and prior drug reactions demonstrated clinically relevant reactions significantly more often. PMID- 2187231 TI - [Cystic adventitional degeneration of the popliteal artery: preoperative diagnosis using imaging technics]. AB - The presented case of cystic adventitial disease of the popliteal artery as a rare cause of intermittent claudication shows the value of modern imaging in establishing the preoperative diagnosis. Besides the characteristics of real-time ultrasound and computerised tomography, the results of angiography and especially functional angiography are discussed and their value towards differential diagnosis is pointed out. PMID- 2187232 TI - [Primary hyperparathyroidism. The first reported case of fibrocystic osteitis]. PMID- 2187233 TI - [Myopathy in uremic patients]. AB - Uremic myopathy seems unfrequently studied although it can be really inconvenient in daily activities for some patients. Its is a proximal and non specific myopathy that should be discriminated from uremic neuropathy. Several disturbances from renal insufficiency have been incriminated but they only play an adjuvant role in regard with renal osteodystrophy. Indeed the presence of myopathy in cases of severe osteodystrophy and its close similarity with myopathies accompanying the different forms of osteomalacia and/or hyperparathyroidism without renal failure suggest that the most important pathogenic factors come from calcium metabolic disorders: excessive parathyroid hormone, vitamin D deficiency, and/or impaired calcium transport. The treatment is subject to the predominant bone lesions: secondary hyperparathyroidism or osteomalacia; but the best attitude remains their prevention. PMID- 2187234 TI - [Obesity and arthritis of the knee]. AB - More than 45 p. cent of patients with degenerative knee arthritis are obese. The overweight is more marked when the medial tibio-femoral and the lateral femoro patellar aspects are affected. With the same degree of weight gain, the relationship between obesity and degenerative knee arthritis is more marked in women than in men. The significance of the overweight increases the probability of developing degenerative knee arthritis, increasing its functional severity. The obesity precedes the arthritis, and is not its consequence. It is a mechanical effect by increase of the articular strains. It is unknown how long the obesity must be present in order to be pathogenic for the knee and what functional and anatomical improvement may be expected from a weight loss. PMID- 2187235 TI - [Polyarthritis disclosing primary biliary cirrhosis with normal hepatic tests. Value of antimitochondral antibodies M2]. PMID- 2187236 TI - [Rheumatoid polyarthritis and deafness. Apropos of a case of oto-arthritis]. PMID- 2187237 TI - [Self-observation of algodystrophy of the arm by the poet and painter Henri Michaux]. PMID- 2187238 TI - Effect of acute vascular fluid volume expansion on erythrocyte sodium transport in essential hypertension. AB - Evidence exists that volume expansion is associated with the appearance of a circulating sodium transport inhibitor. We have evaluated intra-arterial blood pressure (BP), central venous pressure (CVP), plasma renin activity (PRA), intraerythrocyte sodium content, erythrocyte sodium influx and rate constant of sodium efflux in 10 untreated primary hypertensive men (WHO stages I and II). The investigations were done during baseline conditions and after rapid intravenous infusion of 1 litre of saline (0.9% NaCl solution) over 15-20 min. Volume expansion caused an increase in CVP by 6.0 +/- 0.5 cmH2O (p less than 0.01), while BP only exhibited a slight increase. No significant changes in intraerythrocyte sodium content, sodium influx, sodium efflux rate constant or PRA were found after volume expansion compared to baseline. All patients with low normal PRA experienced a decrease in sodium efflux rate constant after volume expansion. We found a positive correlation between baseline PRA and change in sodium efflux rate constant after volume expansion (r = 0.62, p less than 0.05). At baseline the relationship between PRA and intraerythrocyte sodium content nearly reached statistical significance (r = 0.63, p = 0.054). These results may indicate that acute volume expansion influences the release of a circulating factor, modulating sodium transport in low-renin hypertension. PMID- 2187239 TI - Glomerular filtration rate estimated by X-ray fluorescence technique in children: comparison between the plasma disappearance of 99Tcm-DTPA and iohexol after urography. AB - The total plasma disappearance of the non-ionic contrast medium iohexol was determined by X-ray fluorescence technique following intravenous urography in 10 children aged between 2 and 13 years. For comparison the plasma disappearance of 99Tcm-DTPA was estimated both 2 days before and simultaneously with the iohexol study. High correlations between the three sets of data were found and no change in the glomerular filtration rate was detected following injection of contrast medium. It was also found that reliable estimates of the glomerular filtration rate can be obtained from two plasma samples of 1 ml each, taken 3 h and 4 h after the injection of the contrast medium. PMID- 2187240 TI - Epidermal growth factor and haptocorrin in nasal secretion. AB - We report that nasal secretion contains the growth-promoting peptide epidermal growth factor (EGF) and a cobalamin-binding protein. Based on its amino-terminal sequence the cobalamin binding protein is classified as haptocorrin (HC). We have investigated the concentration of these components, the volume secreted, and the concentration of total protein after nasal challenge with methacholine, methacholine + ephedrine, histamine and serotonin. The EGF and HC concentrations do not differ for the four challenge agents employed. Range and median for all values obtained are 0.1-2.5 (0.7) nmol/l (n = 49) for EGF and 50-405 (190) nmol/l (n = 63) for HC. After challenge with methacholine the amount of secretion (80 630 (200) mg (n = 14) and the protein concentration (1.5-7.8 (3.5) g/l (n = 14] are lower than for any other challenge. After challenge with serotonin or histamine the amount secreted is 60-1125 (480) mg (n = 39). The concentration of protein is significantly higher (p less than 0.01) after challenge with serotonin (1.4-56.0 (17.0) g/l (n = 18] than after challenge with histamine (2.0-25.0 (5.0) g/l (n = 20]. PMID- 2187241 TI - High- and low-affinity antibodies--some observations in relation to polyethylene glycol concentration in immunoturbidimetric assays. AB - In an immunoturbidimetric assay it is generally accepted that by increasing the polymer concentration the turbidimetric response is increased when all the other parameters are constant. This is true when working with low-affinity antibodies. When working with high-affinity antibodies some assay systems will produce dose response curves showing decreasing responses with increasing polymer concentrations. These observations are discussed in relation to the time-course of formation of antigen-antibody complexes. PMID- 2187243 TI - [Stabilization surgery of the spine]. AB - New diagnostic tools and alternatives such as CAT-scan, NMRI, discography, functional X-rays, infiltrations and immobilization tests have made spinal instability a more rational diagnosis than it was only a few years ago. Neurological deficit, radicular pain and pseudo-radicular pain may only be an expression of instability and are best treated by stabilizing operations. Laminectomy has few indications and is not a logical procedure, especially if used as decompression of the dural sac in tumor involvement of the spine, which usually comes from the front (vertebral body). Therefore, anterior surgery is indicated rather than so-called posterior decompression. In accordance with osteosynthesis techniques of limb disorders, high stability can be achieved through special implants, on the basis of a better understanding of the biomechanics of implants and the healthy and impaired spine. Short fusion and fixation have therefore become a principle which is the standard of reference for present and future spinal surgery. The spectrum of indications for spinal surgery has vastly increased in the last few years, though exact diagnosis is mandatory for optimal treatment. PMID- 2187242 TI - [Placebo action and alternative medicine]. AB - Experimental and clinical data concerning placebo effects on pain states and other subjective symptoms are summarized, and show that placebo treatment and psychotherapy are identical. The drugs used by anthroposophical physicians, homeopaths, phytotherapists and therapists attempting to "normalize" the intestinal bacterial flora are in fact pure or impure placebos. Since official medicine is well aware of the scientific basis and favourable results of placebo treatment in psychosomatic and self-limiting diseases, it does not appear necessary to integrate varieties of alternative medicine into graduate and postgraduate medical training. PMID- 2187244 TI - Venous thromboembolic disease in pregnancy. PMID- 2187245 TI - The pregnant asthmatic patient. PMID- 2187246 TI - Pregnancy associated with systemic lupus erythematosus. AB - Lupus pregnancies may be complicated by difficulties in the diagnosis of flare, by complications related to aPL antibody, complications related to neonatal lupus, and by a high frequency of preeclampsia. Lupus pregnancies are often difficult to manage, but most complications can be anticipated and, with care, successfully managed. PMID- 2187247 TI - Antiphospholipid antibodies and pregnancy: maternal implications. AB - Antiphospholipid antibodies are associated with a spectrum of serious medical conditions. Several of these are of special concern to the obstetrician because they have a tendency to occur during pregnancy. Untreated pregnant women with aPLA appear to be especially prone to thrombotic events, including stroke. Atypically early-onset preeclampsia occurs in a large proportion of women with aPLA and a history of pregnancy loss. Conversely, a modest proportion of women with early-onset preeclampsia have aPLA. Although rare, a syndrome of postpartum pleuropulmonary disease and thrombosis is associated with aPLA. Finally, certain neurologic conditions, such as TIAs and chorea gravidarum, appear to be related to aPLA. It is important to recognize pregnant women with aPLA so they can be appropriately managed in an effort to avoid fetal loss and thromboembolic events. PMID- 2187248 TI - Pathophysiology of preeclampsia. AB - In summary, the major pathophysiologic event that occurs in women with preeclampsia or pregnancy-induced hypertension is vasospasm. In turn, vasospasm leads to a wide range of dysfunction in many organ systems. PMID- 2187249 TI - Physiology of low-dose aspirin therapy for the prevention of preeclampsia. PMID- 2187250 TI - Sexually transmitted diseases in pregnancy. AB - STDs can be one of the most common antepartum complications in high-risk gravidas. Screening for gonorrhea, syphilis, HPV, and possibly hepatitis B and chlamydial infection, should be considered in most, if not all, pregnant women. Familiarity with the common clinical presentations and treatment of bacterial STDs will prevent untoward maternal and neonatal outcome. Recognition of viral STDs, followed by appropriate counseling and management, will avoid most neonatal viral infection. PMID- 2187251 TI - Substance abuse in pregnancy. AB - The number of women who abuse drugs during pregnancy is unknown, but as many as 375,000 infants may be affected. Although some substances appear to result in less damage than others, it is impossible to differentiate individual effects because of the common use of multiple substances. The potential for synergy among substances with similar physiologic effect is an additional factor. The immediate perinatal effects of substance abuse are often obvious; it is the long-term effects that we have only recently begun to examine. These long-term effects will involve both the individual and society. PMID- 2187252 TI - The diagnosis and management of hemoglobinopathies during pregnancy. AB - Patients with hemoglobinopathies can be at risk for significant maternal and fetal morbidity during pregnancy. This is especially true for those gravidas with SCD or certain thalassemia disorders. With intensive management, pregnancy outcome for these women has improved dramatically, and approximates that of the general population. Criteria for diagnosis for many of these conditions are well established. Appropriate therapeutic interventions are more controversial, but, regardless, emphasize the need for a heightened awareness of these disorders and their potential complications. PMID- 2187253 TI - [The clinical value of panorama zonography]. PMID- 2187255 TI - Escherichia coli O157:H7 haemorrhagic colitis. Report of the first South African case. AB - Escherichia coli O157:H7, although recognised 15 years ago, has only become a significant pathogen since 1982 when two outbreaks of haemorrhagic colitis due to this organism were described in the USA. Since then, numerous such outbreaks have been reported. Recent experience with a patient presenting with E. coli O157:H7 induced haemorrhagic colitis is described. The main features, pathological findings and investigations are described and the principles of management outlined. PMID- 2187254 TI - D. J. du Plessis lecture. A question of living. PMID- 2187256 TI - Relative erythromycin resistance in Streptococcus pyogenes. PMID- 2187257 TI - Development, morphology, and function of the yolk-sac placenta of laboratory rodents. AB - A review of current knowledge of the unusual structure and several functions of the yolk-sac membranes of common laboratory rodents, viz., rats, mice, hamsters, guinea pigs and gerbils, enables a better assessment of the significance of this maternofetal exchange system in the experimental production of congenital anomalies. The anatomy of both visceral and parietal walls of the rodent yolk-sac placenta--specifically the anatomical relationships of each wall with maternal and with other fetal tissues--depends on the mode of origin and subsequent development of the yolk sac in these several species. Accordingly, the developmental biology of the rodent yolk sac is described. Since both fine structure and anatomical relationships also determine in large measure the functioning of the membrane as a whole in the absorption of selected materials either for intracellular digestion or for cellular translocation and transport to the developing embryo, the anatomy of the yolk sac is considered in detail. Similarly, since available evidence strongly suggests that teratogenic agents induce perturbations in the cellular mechanisms that control these several functions of the yolk-sac placental system in the production of birth defects, additionally an account is given of the cell biology of the membrane, i.e., endocytosis and targeting/trafficking of materials either for digestion within the epithelium at the maternal surface of the visceral yolk sac or for translocation across the yolk-sac membrane as a whole. PMID- 2187258 TI - Cell physiology of the rat visceral yolk sac: a study of pinocytosis and lysosome function. AB - The rat visceral yolk sac is active in pinocytosis. Macromolecules accumulated by the tissue are, in general, routed to the lysosomes, where they either accumulate (if non-digestible by the lysosomal enzymes) or are degraded to their monomeric components. The yolk sac cells engage in adsorptive pinocytosis, which leads to the preferential uptake of macromolecules bearing certain surface features, such as a hydrophobic or a cationic domain. Substrates that enter the yolk sac by adsorptive pinocytosis can in some cases act as bivalent ligands, carrying in a second substance by "piggy-back" pinocytosis. Pinocytosis and intralysosomal digestion of plasma proteins by the organogenesis-stage rat embryo play an important nutritional role, supplying a high proportion of the embryo's amino acid requirement. Teratogenic effects can be induced by substances that inhibit either pinocytosis or intralysosomal proteolysis at this sensitive stage of gestation. PMID- 2187259 TI - Experimental manipulation of the rodent visceral yolk sac. AB - The visceral yolk sac (VYS) is an especially important placental organ in the rodent because it is the primary source of exchange between the embryo and mother during early organogenesis before the chorioallantoic placenta circulation is established. The VYS is involved with nutritional, endocrine, metabolic, immunologic, secretory, excretory, and hematopoietic functions. The VYS also plays a role in steroid metabolism and interacts with a variety of blood-borne factors: parathyroid hormone, glucocorticoids, insulin, and vitamin D metabolites. The importance of the VYS during development is emphasized by the embryotoxicity resulting from exposure to agents which cause VYS dysfunction when administered to the pregnant animal during organogenesis. Several experimental procedures have provided useful information concerning a variety of VYS functions from early organogenesis to term: Culture of the Embryo, Fetal Incubation, Culture of the Fetus, Giant Yolk Sac, Short- and Long-Term Culture of the Yolk Sac, Modified Ussing's Chamber, Single or Double Diffusion Chamber, and the use of Heterologous Rodent Visceral Yolk Sac Antibodies. Since human yolk sac pathology has been associated with developmental toxicity and spontaneous abortion, it is important to discover whether there are some common functional roles among different mammalian species and to determine if other experimental animal models can be used to study the possible contribution of human yolk sac dysfunction to some human reproductive problems. PMID- 2187260 TI - Experimental yolk sac dysfunction as a model for studying nutritional disturbances in the embryo during early organogenesis. AB - Our investigations concerning the importance of cell surface macromolecules during embryonic development led us to the discovery in 1961 that heterologous anti-rat kidney serum produced teratogenesis, growth retardation and embryonic death when injected into the pregnant rat during early organogenesis. It was established that IgG was the teratogenic agent, primarily directed against the visceral yolk sac (VYS) but not the embryo. Heterologous anti-rat VYS serum was prepared which was teratogenic localized in the VYS and served as a model for producing VYS dysfunction and embryonic malnutrition. The role of the yolk sac placenta in histiotrophic nutrition is now recognized to be critical for normal embryonic development during early organogenesis in the rodent. VYS antiserum affects embryonic development primarily by inhibiting endocytosis of proteins by the VYS endoderm, resulting in a reduction in the amino acids supplied to the embryo. Our laboratory has recently developed teratogenic monoclonal yolk sac antibodies (MCA) which can be utilized; to study VYS plasma membrane synthesis and recycling, to compare yolk sac function among different species, and to identify components of the plasma membrane involved in pinocytosis. MCA prepared against certain VYS antigens provide an opportunity to study embryonic nutrition with minimal interference with the nutritional state of the mother. Recent developments in the study of the human yolk sac along with our laboratory's ability to isolate a spectrum of yolk sac antigens, prepare monoclonal antibodies, and perform functional studies, should provide information that will increase our understanding of yolk sac function and dysfunction in the human and determine the relative importance of various amino acids to normal development during mammalian organogenesis. PMID- 2187261 TI - [Comments on some aspects of pediatric and adolescent psychiatry]. AB - Child and adolescent psychiatry of today is closely connected with adult psychiatry, pediatrics, developmental psychology and education. It finds itself in multipolar tension-fields and is in need of a constant bridging towards the allied professions, especially child care. Besides biological and psychological factors, historical, social and cultural influences deeply affect diagnostic and therapeutic procedures concerning disturbed children and adolescents. In the field of research there is a lack of structures and means. PMID- 2187262 TI - [Gerontopsychiatry--psychiatry for the aged]. AB - The multimorbidity is increasing with high age. The number of elderly and especially of the very old is going to increase in the next decades. This leads to a necessity to introduce more profound undergraduate and postgraduate training for those who are likely to work with and care for the elderly. The following article describes in detail the most important psychiatric disturbances in the old age, their etiology--as far as we know it--, clinical picture and treatment possibilities. PMID- 2187263 TI - [Drug-dependent patients in general practice]. AB - Contrary to the popular opinion of many physicians, addicts are primarily seeking help in the practice. The treatment of addicts in the practice requires an early diagnose. The competence of treatment needs a sensible part, concerning the knowledge about the potential of dependence and the following symptoms, the withdrawal medication and the relapse situations, and an emotional part, concerning personal attitude towards personal vulnerability to face relapses. It is desirable to develop liaison services between physicians in practice and the specialists to improve the efficiency of treatment. PMID- 2187264 TI - [Possibilities of cognitive behavior therapy in general practice]. AB - Cognitive behavior therapy has achieved an important standing among the various approaches in psychotherapy. The article gives a short overview over the history of cognitive behavior therapy and delineates its applications in psychotherapy, especially in the treatment of mild to moderate depressions. Further indications include the treatment of anxiety disorders, as well as in the skills training and self-management of schizophrenic patients. Therapeutic experience underscores the importance of a multimodal concept, embedded in a trusting therapeutic relationship. Cognitive behavior therapy must not be viewed as mere therapeutic technique but rather as a therapeutic attitude with the goal of helping the patient achieve better self-efficacy. PMID- 2187265 TI - [The general practitioner in relation to social psychiatric concepts of schizophrenia treatment]. AB - In the last 30 years the traditional concept of schizophrenia has changed basically because of epidemiological investigations and studies on expressed emotion and on life-events. The concept of vulnerability in schizophrenia distinguishes stress and protection factors. As a consequence to social psychiatry, psychiatric clinics got smaller, and new outpatient facilities were created. In the treatment of schizophrenic patients, the general practitioner has an important role. Some practical concepts of therapy are discussed. PMID- 2187266 TI - [Naltrexone--an effective aid in the psychosocial rehabilitation process of former opiate dependent patients]. AB - Naltrexon is an longterm opioid antagonist, which can be used in the psychosocial rehabilitation process of former dependents on opiates. It was established that there were less opiates used during the treatment with Naltrexon. The exclusive delivery of Naltrexon cannot protect from relapse and has to be completed with psychotherapeutic measures. PMID- 2187267 TI - [Hemodynamic modifications induced by urapidil in man]. PMID- 2187268 TI - [Metabolic and cardiovascular profile in antihypertensive treatment with urapidil]. PMID- 2187270 TI - Impedance plethysmography or real-time ultrasonography in the diagnosis of venous thrombosis in pregnant women. PMID- 2187269 TI - Animal tumor procoagulants: registry of the Subcommittee on Haemostasis and Malignancy of the Scientific and Standardization Committee, International Society of Thrombosis and Haemostasis. PMID- 2187271 TI - [Somatic and biochemical complications in bulimia]. AB - Bulimia is an eating disorder characterized by binge eating followed by purging, i.e. self-induced vomiting, abuse of cathartic or diuretic drugs, increased activity or periods of restrictive dieting. Studies show that persons with bulimia are prone to a number of medical complications as a result of binge eating, vomiting and drug abuse. Vomiting is the most harmful in terms of medical risk, and also the most common source of complications. Both vomiting and purging lead to loss of body fluids and electrolytes, often resulting in hypokalemia. Vomiting also leads to sore throats and dental problems such as destruction of enamel. Gastric dilatation is the only complication directly associated with binge-eating. Harmless symptoms, such as abdominal pain, diarrhoea, constipation and neuromuscular symptoms are common. This article discusses the pathophysiology behind the complications and their treatment. PMID- 2187272 TI - [Peroral emptying of the colon. A randomized comparison of 4 and 1.5 liter regimens]. AB - A "clean" colon is needed for adequate endoscopic examination. In order to examine patients' acceptance of two different regimens taken orally, and their efficacy, 32 patients in an outpatient clinic were randomized either to a four litre regimen of a solution of electrolytes and polyethylenglycol or a 1.5 litre regimen supplemented with bisacodyl. The patients' acceptance was better for the 1.5 litre regimen, since only one out of 17 patients failed to drink the solution, while four out of 15 patients were unable to complete drinking the four litres. Insufficient cleaning of the colon caused inadequate examination in four patients. All patients who had followed the four litre regimen were examined successfully. We conclude that the present 1.5 litre regimen is insufficient as pretreatment for colonoscopy. PMID- 2187273 TI - [Ultrasonography-guided biopsy in cancer]. PMID- 2187274 TI - [Do we need more ACE inhibitors?]. PMID- 2187275 TI - [Bacterial adhesion. An important pathogenetic factor]. AB - Bacterial adherence is usually the first step of an infection. Bacteria bind to receptors on cell surfaces by different adhesins like fimbriae, fibrillae or lipoteichoic acid. The reseptors may be glucolipids, with sugar molecules like galactose (Gal-Gal), and present on the mucosa of the urinary tractus. Other receptors are glucoproteins or fibronectin. Important non-specific receptors are foreign material or implants in the body. Symptoms of infection generally occur from bacteria that are a) only adherent, b) adherent and toxin producing, or c) adherent and then invasive. Urogenital, gastrointestinal or respiratory tract infections are often caused by adherent bacteria. Adherent bacteria may also play an important role in infections of newborns. Invasive bacteria seem to be able to switch off their adhesins, or cover them by capsulae or human proteins, when such is necessary in order to escape human defendence mechanisms. PMID- 2187276 TI - [The personal computer for administrative routines at a radiology department]. AB - The article describes a radiological information system (RIS) developed by members of the medical staff at a university hospital. Software has been developed on the basis of the two common databases; dBASE III plus and Clipper. The system is modular constructed. Each module can be operated individually, but best function is obtained by networking in a Ethernet (3Com). The article describes the different modules, user experience and future plans for development. PMID- 2187277 TI - [Incidence and mortality of uterine cervix cancer in Norway. When do we get organized nation-wide cytologic screening in Norway?]. AB - In 1975 and 1985 the Norwegian Ministry of Health appointed a committee to evaluate the value of cytological examination of the uterine cervix in Norway. Both committees recommended that all Norwegian women aged 20/25 to 69 should be examined every three years. The reduction in incidence of cervical cancer and the mortality from the disease has been very slight compared to the reduction in the other Nordic countries where, in contrast to Norway, organized screening has been carried out on a large scale. There are no objections to an immediate organization of a national screening programme in Norway, either from the medical or the economic point of view. PMID- 2187278 TI - A more stringent and longer-term standard for tropospheric ozone. Emerging new data on health effects and potential exposure. PMID- 2187279 TI - The effect of stepwise iodination on biological properties of Bothrops jararaca venom. AB - By titrating 5 mg of native venom with aliquots of a 2 x 10(-2) M iodine monochloride solution, neutralization of lethality by the incorporation of iodine was found with 200 +/- 5 microliters of solution, and above, up to 310 +/- 10 microliters, when saturation with iodine was attained. Doses up to 1500 micrograms (equivalent to 32 LD50 of native venom), where injected i.p. in mice without lethal effects. Proteolytic, phospholipase A2 and esterolytic activities were greatly reduced, but a low activity persisted even in fully iodinated samples. Direct hemolysis was markedly inhibited, and incapacity to coagulate fibrinogen and horse plasma was also observed in the iodinated samples. Hemorrhage and necrosis in rat skin, caused by 20 micrograms of iodinated venom were not elicited by doses up to 120 micrograms of iodinated anavenom. In mice, the myonecrosis that resulted from direct i.m. injection of native venom, and the massive hemorrhage caused by 5 LD50 doses injected i.p. were abolished by venom iodination. Blood congestion in liver, spleen, kidneys, and lungs, almost disappeared with iodination to the level of neutralization, and was barely seen with venom samples iodinated to saturation. The clinical signs of impaired physical activity, appearing in mice injected with 700 to 1500 micrograms of the iodinated anavenom were intensified by captopril and attenuated by epinephrine. PMID- 2187280 TI - Pathogenic factors in aminoglycoside-induced nephrotoxicity. AB - Aminoglycoside antibiotics play an integral role in antimicrobial chemotherapy. Unfortunately, these drugs are known to cause nephrotoxicity in man and experimental animals. In fact, the incidence of renal dysfunction during the course of clinical treatment with aminoglycoside antibiotics is approximately 10%. Over the past two decades the elucidation of the pathogenesis of aminoglycoside-induced nephrotoxicity has been the subject of numerous investigations. This review describes the recent theories postulated to play a role in the pathogenesis of antibiotic-induced renal damage. In particular, the importance of amino-glycoside levels in the renal cortex or at the membrane binding site is examined in detail. The relevance of antibiotic tissue levels is reflected in the ability of other drugs to modify nephrotoxicity through an alteration in renal aminoglycoside content. The role of factors including age and diet in drug-induced nephrotoxicity is described. In clinical practice, aminoglycoside antibiotics may often be with other agents. The influence of aminoglycoside interaction with other drugs including vancomycin, cephalosporins and cytotoxic drugs is examined in the light of reports that nephrotoxicity is potentiated in these situations. In addition, this review focuses on the role of infection (pyelonephritis and septicemia) and bacterial endotoxin as pathogenic factors involved in aminoglycoside nephrotoxicity. Both the direct influence of endotoxin and the indirect effects of vasoactive mediators and inflammatory processes will be discussed. A multiplicity of factors is involved in the pathogenesis of aminoglycoside-induced nephrotoxicity and these are further amplified in the presence of infection. PMID- 2187281 TI - Reappraisal of the findings on Agent Orange by the Australian Royal Commission. PMID- 2187282 TI - Stable isotope labeling in steroid research: a historical perspective. PMID- 2187283 TI - Studies on estrogen biosynthesis using radioactive and stable isotopes. AB - The conversion of androgens into estrogen involves three distinct generic reactions which are catalyzed by a single P450 enzyme (aromatase or P450(aromatase)). The first step in the process is the conversion of 19-methyl into a hydroxymethyl group which requires NADPH + O2, thus representing the well known hydroxylation process. The next stage, converting the -CH2OH into -CHO, also requires NADPH + O2 and may be rationalized either through a second hydroxylation reaction producing a gem-diol, CH(OH)2 (which dehydrates to the aldehyde), or via another route. The final stage in the process again uses NADPH + O2, culminating in the release of C-19 as formate. Our extensive studies using precursors containing 2H, 3H, and 18O have shown that the carbonyl oxygen of the 19-aldehyde group is the one that was introduced in the first step as the hydroxyl group. The aldehydic oxygen along with another, from O2, used in the third step of the process, is incorporated into the released formate. It was found that at each stage of the process, oxygen atoms were introduced or transferred as "whole numbers." In light of these data, mechanisms in which H2O is used to promote the C-10-C-19 bond cleavage or those in which the conversion of the 19-oxoandrostenedione into estrogen is considered to occur via the sequence -CHO----(-)CH(OH)2----estrogen are eliminated. In addition, our mechanistic analysis makes it unlikely that 1 beta-, 2 beta-, or 10 beta hydroxysteroids serve as intermediates in estrogen biosynthesis. We consider a free radical mechanism for the hydroxylation process. PMID- 2187284 TI - Cortisol production rates measured by liquid chromatography/mass spectrometry. AB - Cortisol production rates (FPRs) in physiologic and pathologic states in humans have been investigated over the past 30 years. However, there has been conflicting evidence concerning the validity of the currently accepted value of FPRs in humans (12 to 15 mg/m2/d) as determined by radiotracer methodology. The present study reviews previous methods proposed for the measurement of FPRs in humans and discusses the applications of the first method for the direct determination of 24-hour plasma FPRs during continuous administration of a stable isotope, using a thermospray high-pressure liquid chromatography-mass spectrometry technique. The technique is fast, sensitive, and, unlike gas chromatography-mass spectrometry methods, does not require derivatization, allowing on-line detection and quantification of plasma cortisol after a simple extraction procedure. The results of determination of plasma FPRs by stable tracer/mass spectrometry are directly in units of mass/time and, unlike radiotracer methods, are independent of any determination of volume of distribution or cortisol concentration. Our methodology offers distinct advantages over radiotracer techniques in simplicity and reliability since only single measurements of isotope ratios are required. The technique was validated in adrenalectomized patients. Circadian variations in daily FRPs were observed in normal volunteers, and, to date, results suggest a lower FRP in normal children and adults than previously believed. PMID- 2187285 TI - Stable isotope methodology in the pharmacokinetic studies of androgenic steroids in humans. AB - The use of stable isotopically labeled steroids combined with gas chromatography/mass spectrometry (GC/MS) has found a broad application in pharmacologic studies. Initially, stable isotopically labeled steroids served as the ideal analytic internal standard for GC/MS analysis; however, their in vivo use has expanded and has proven to be a powerful pharmacokinetic tool. We have successfully used stable isotope methodology to study the pharmacokinetic/bioavailability of androgens. The primary advantage of the technique is that endogenous and exogenous steroids with the same basic structure can be differentiated by using stable isotopically labeled analogs. The method was used to examine the pharmacokinetics of testosterone and testosterone propionate, and to clarify the influence of endogenous testosterone. Another advantage of the isotope methods is that steroidal drugs can be administered concomitantly in two formulations (e.g., solution and solid dosage). A single set of blood samples serves to describe the time course of the formulations being compared. This stable isotope coadministration technique was used to estimate the relative bioavailability of 17 alpha-methyltestosterone. PMID- 2187286 TI - Simultaneous quantification of several cholesterol autoxidation and monohydroxylation products by isotope-dilution mass spectrometry. AB - An assay based on isotope-dilution mass spectrometry with deuterium-labeled internal standards was developed for simultaneous quantification of cholest-5-ene 3 beta,7 alpha-diol (7 alpha-hydroxycholesterol), cholest-5 beta,6 beta-epoxy-3 beta-ol (cholesterol-5 beta,6 beta-epoxide), cholest-5 alpha,6 alpha-epoxy-3 beta ol (cholesterol-5 alpha,6 alpha-epoxide), cholest-5-en-7-one-3 beta-ol (7 oxocholesterol), cholestane-3 beta,5 alpha,6 beta-triol, cholest-5-ene-3 beta,25 diol (25-hydroxycholesterol), and cholest-5-ene-3 beta,26-diol (26 hydroxycholesterol) in one single serum sample. Recovery experiments and replicate analyses showed that the assay was sufficiently sensitive, accurate, and precise. The concentrations of the listed compounds in sera from 19 healthy subjects were determined and are presented. PMID- 2187287 TI - Stroke in infective endocarditis. AB - We reviewed 212 consecutive episodes of infective endocarditis in 203 patients at six hospitals between 1978 and 1986 and found that 21% were complicated by stroke. Of 133 episodes involving native mitral and/or aortic valves, brain ischemia occurred in 19%, brain hemorrhage in 7%, and non-central nervous system emboli in 11%; vegetations were identified in 56% of 113 adequate echocardiograms and did not correlate with risk of embolism. In native-valve endocarditis, most (74%) ischemic strokes had occurred by the time of presentation and an additional 13% occurred less than or equal to 48 hours after diagnosis; the incidence of brain ischemia was 13% on presentation, 3% during the first 48 hours of hospitalization, and 2%-5% during the remainder of the acute course. Stroke recurred at a rate of 0.5%/day, often heralding relapse/uncontrolled infection. Only 9% of ischemic infarcts were large (all in patients with Staphylococcus aureus infection), while 8% were small and subcortical. Brain hemorrhage occurred primarily at the time of presentation, particularly in intravenous drug abusers, and was associated with uncontrolled S. aureus infection with pyogenic arteritis. Ischemic and hemorrhagic stroke continue to be frequent and important in patients with infective endocarditis and are clustered during uncontrolled infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2187288 TI - Alcohol consumption and carotid atherosclerosis in the Lausanne Stroke Registry. AB - We evaluated the association between alcohol consumption and carotid atherosclerosis in 261 consecutive patients greater than 50 years old admitted to our community-based primary-care center with first ischemic stroke; their characteristics were entered into a computerized data bank (Lausanne Stroke Registry). Reported regular alcohol consumption was compared with the presence and severity of internal carotid artery disease as assessed by duplex scanning with spectral analysis of the Doppler signal and real-time B-mode imaging at the level of the carotid bifurcation. We found an inverse linear relation between light-to-moderate alcohol intake (less than or equal to 4 standard drinks/day) and severity of internal carotid artery stenosis. No conclusion could be drawn for heavier drinkers because there were too few. A logistic regression model showed that hypertension, cigarette smoking, and age in men and diabetes mellitus and cigarette smoking in women strongly counterbalanced the potential benefit of alcohol consumption. Although regular alcohol drinking cannot be advocated on the basis of our findings, light-to-moderate consumption of alcohol is the first factor to be inversely associated with extracranial carotid atherosclerosis in symptomatic patients with cerebrovascular disease. PMID- 2187289 TI - Duplex Doppler and spectral flow analysis of racial differences in cerebrovascular atherosclerosis. AB - We compared carotid artery disease in 99 black and 106 white patients using duplex ultrasonography (B-mode imaging and Doppler spectral analysis). Blacks had significantly less stenosis of the extracranial internal carotid artery than whites. Among the risk factors investigated, hypertension alone, ischemic heart disease, diabetes mellitus, and smoking failed to explain the racial difference. Although carotid stenosis of greater than or equal to 40% correlated significantly with age in both races (p = 0.001 in whites and p = 0.005 in blacks), blacks had significantly less carotid stenosis of any degree even when age was taken into account. Multivariate analysis showed that race is a significant and independent risk factor for carotid stenosis (p less than 0.0001). Hypertension interacting with race was also significant. Our results require verification in population-based studies. Carotid duplex ultrasonography offers a noninvasive method for carrying out such studies. PMID- 2187290 TI - Anticoagulation: is there still a role in atherothrombotic stroke? PMID- 2187291 TI - Intracellular membrane fusion in cell-free systems. PMID- 2187292 TI - Insights into membrane insertion based on studies of colicins. AB - The recently determined three-dimensional structure of the pore-forming domain of colicin A has led to a hypothetical model for membrane insertion and channel formation. Certain features of this model have implications for understanding the mechanism of membrane insertion by other toxins and may have a broader relevance to protein transport in general. PMID- 2187293 TI - The measurement and mechanism of lipid peroxidation in biological systems. AB - The basic chemistry of the propagation of lipid peroxidation reactions has been known for years, but the mechanism of initiation of this process in biological membrane systems is still uncertain. Currently available assays for measuring peroxidation are reviewed--the more specific the assay used, the less peroxide is found in healthy human tissues and body fluids. Lipid peroxidation can arise as a consequence of tissue injury in many disease states and may sometimes contribute significantly to worsening the tissue injury. PMID- 2187294 TI - Prenyl proteins in eukaryotic cells: a new type of membrane anchor. AB - Recent studies have indicated that eukaryotic cells contain proteins that are post-translationally modified by long-chain, thioether-linked prenyl groups. These proteins include yeast mating factors, ras proteins and nuclear lamins. The modification occurs on a cysteine residue near the C terminus and appears to initiate a set of additional protein modification reactions that promote attachment of the proteins to specific membranes. PMID- 2187295 TI - Involvement of an initiation factor and protein phosphorylation in translational control of GCN4 mRNA. AB - Regulation of the GCN4 gene of Saccharomyces cerevisiae is one of the best documented instances of gene-specific translational control in an eukaryote. Upstream open reading frames (uORFs) in GCN4 mRNA modulate the flow of scanning ribosomes to the GCN4 start codon according to the availability of amino acids. Recent results suggest that sequences at the termination codons of the uORFs, a general initiation factor, and a protein kinase all make important contributions to the proper functioning of this interesting translational-control element. PMID- 2187296 TI - Molecular genetics of polyamine synthesis in eukaryotic cells. AB - The polyamines putrescine, spermidine and spermine are important cellular constituents involved in the regulation of cell growth and differentiation. Their intracellular levels are regulated by a multitude of mechanisms affecting their synthesis, degradation, uptake and excretion. As a result of the application of molecular biology techniques, some of these mechanisms are presently being unravelled, and are providing a basis for the rational development of novel agents effective against proliferative disorders and various parasitic diseases. PMID- 2187298 TI - Morphometrically estimated variation in nuclear size. A useful tool in grading prostatic cancer. AB - At present there are several grading systems for prostatic carcinoma. Most are difficult to reproduce. An objective method of grading seems to be necessary and could make comparisons between various groups of patients easier and grading more reliable. In the present study morphometrically estimated nuclear size and variation in nuclear size are matched with the survival rates of 207 patients who underwent total perineal prostatectomy for cancer. On the basis of morphometrically estimated variation in nuclear size the patients could be divided into two groups with significantly differing survival rates. In this way it was possible to split the group of patients with grade 2 carcinoma (Mostofi's grading system) into two groups of patients with significantly different survival rates. The survival rates in these two groups did not differ significantly from those in the patients with Grade 1 and Grade 3 tumors respectively. The results are discussed in the light of the recent literature on the subject. Morphometry seems to be a valuable tool in grading prostatic cancer. PMID- 2187297 TI - Placental-like alkaline phosphatase in seminoma. AB - Tumor marker identification in testicular cancer has contributed to early detection and monitoring of non-seminomatous disease. A placental alkaline phosphatase-like (PLAP-like) enzyme derived from seminomas has recently been focused upon as a possible marker for this disease. The biochemistry of the PLAP like enzyme is reviewed, as well as its occurrence in tissue and sera from healthy persons and patients with testicular cancer. PMID- 2187299 TI - Development of monoclonal antibodies against canine glomerular antigens. AB - Monoclonal antibody producing hybridomas were developed by fusing spleen cells from BALB/c mice immunized against canine glomeruli with SP2 myeloma cells. Monoclonal antibody reactivity was tested using an indirect immunofluorescence assay on various normal canine tissues and canine kidney affected with glomerulonephritis. Two of the hybridomas developed (3H2 and 3A5) reacted with glomeruli and not with renal tubules. Antibody produced by hybridoma 3A5 also reacted with smooth muscle of all other tissues tested and 3H2 with lung tissue. Antigens recognized by monoclonal antibodies were studied by assessing their heat stability and susceptibility to proteolysis and neuraminidase digestion. Antigen and antibody molecular weights were determined by using a western blotting technique. Glomerular proteins that reacted with antibody produced by hybridoma 3H2 had molecular weights ranging from approximately 92,500 daltons to 200,000 daltons. Antigens reacting with both monoclonal antibodies were likely protein antigens. It was concluded that monoclonal antibodies would be useful in the study of glomerular antigens in normal dogs and dogs with glomerulonephritis. PMID- 2187300 TI - Fourth French Consensus Conference on intensive care and emergency medicine. Selection of a fluid for vascular expansion in the treatment of hypovolemia in adult patients. PMID- 2187301 TI - Blood group terminology 1990. The ISBT Working Party on Terminology for Red Cell Surface Antigens. PMID- 2187302 TI - Autologous transfusion practice. Controversies about current fashions and real needs. PMID- 2187303 TI - [The efficacy of the captopril treatment of elderly hypertension patients]. AB - It was established that monotherapy with captopril was effective in 72% of patients with hypertensive disease in the elderly. Reduction of the arterial pressure is accompanied by an improvement of the indices of hemodynamics and myocardial contractility as well as relaxation of the left ventricle. Captopril proved more effective in patients with a high concentration of blood angiotensin. Acute load by a single intake of 25 mg of captopril may with high probability predict the efficacy of treatment courses, namely, in patients with a good clinical efficacy reduction of the preparation. Captopril is recommended for the treatment of hypertensive disease in the elderly. PMID- 2187304 TI - [The antimicrobial properties and use of sulfochloranthine (a review of the literature)]. PMID- 2187305 TI - [Hypertensive crises (a review of the literature)]. PMID- 2187306 TI - [The use of echo- and scintigraphic study of the biliary system in chronic cholecystitis]. AB - Data are reported of a study of the functional state of the biliary in 50 patients with chronic cholecystitis by means of complex employment of dynamic echo- and cholecystography and dynamic computerized gamma hepatobilioscintigraphy. It was found that dynamic echo- and cholecystography proved highly efficient indicating that ultrasound tomography is of importance not only the diagnosis of structural but also functional disorders in cholecystitis, for the choice of optimal tactics and evaluation of the efficacy of therapeutic measures excluding radiation treatment. PMID- 2187307 TI - [Erythrocytic changes in diabetes mellitus (a review of the literature)]. PMID- 2187308 TI - [20 years of gastroenterological endoscopy. 1967-1987]. PMID- 2187309 TI - [Scleroderma]. AB - Sclerodermas may occur in two basic forms: localized sleroderma (LSc) and systemic scleroderma (SSc). Pseudoscleroderma as well as overlap syndromes have to be differentiated from these two variants. From the clinical point of view, localized scleroderma can be subdivided into type I = plaque-like LSc (= morphea), type II = linear LSc, and type III = deep LSc. According to the degree of the cutaneous involvement, systemic scleroderma can likewise be classified into type I = sclerodactylia, type II = acrosclerosis, and type III = scleroderma with primary involvement of the trunk (diffuse scleroderma). In LSc, we never find systemic involvement; SSc, in contrast, is almost always associated with Raynaud's phenomenon, changes of the esophagus, as well as an increased titer of antinuclear antibodies (Hep-2 cell test). Only 23% of our patients with LSc showed elevated ANA titers. We present and discuss data of 56 patients with LSc and 52 patients with SSc. Evidence in the literature as well as our own findings suggest that the pathogenesis of LSc is different from that of SSc. The influence of various mediators and cytokines on the collagen metabolism might be regarded as a theoretical approach in order to develop new therapeutic regimens. This is even more important since there is still no efficient mode of treatment for neither localized nor systemic scleroderma. PMID- 2187310 TI - [The effect of initial external glucocorticoid administration on cignolin treatment of psoriasis]. AB - In a randomized open study we compared the effect of conventional dithranol therapy (CSV-therapy, 7 patients) with a combination regimen, in which patients were pretreated with a 0.064% betametason dipropionate ointment (Diprosis) for 1 week before the onset of dithranol therapy (B + CSV-therapy). Clinical evaluation was performed by grading 4 representative lesions per patient for erythema, plaque thickness and scaling every week (EPS-score). After one week of therapy glucocorticoid was superior to dithranol (reduction of EPS-scores 68% vs. 35%). Thereafter the benefit of CSV-therapy surpassed that of B + CSV-therapy. 33 days after onset of therapy there was a 95% reduction of skin lesions in the CSV-group compared to a 75% reduction in the B + CSV-group. In terms of a 95% reduction the CSV-group required 32.9 +/- 5.5 days versus 45.1 +/- 19.7 days of the B + CSV group. During the 6 months follow-up relapses occurred in 3 of 7 patients of the CSV-group 15.32 and 34 days after discontinuation of therapy and in 2 of 7 patients of the B + CSV-group 64 and 82 days after discontinuation of therapy. The present findings reveal that a pretreatment of psoriasis with topical glucocorticoids reduces the response to dithranol and the duration of remission. PMID- 2187311 TI - [The epidermis as metabolically active tissue: regulation of lipid synthesis by the barrier function]. AB - Numerous investigations have shown that the lipids of the horny layer play an important role in the epidermal barrier function. These lipids consist of sphingolipids, cholesterol, and free fatty acids in nearly equimolar proportions. If the barrier function is disturbed--i.e. in case of lipid extraction or a diet deficient of essential fatty acids--we find an increased synthesis of free fatty acids, cholesterol, and non-saponifiable lipides in the epidermis. Covering the skin with a Latex wrap prevents an increased lipid synthesis. The synthesis of cholesterol depending on the barrier function is regulated by the enzyme HMG CoA reductase. The regulation process involves both the quantity and the activity (phosphorylation) of the enzyme. Acute disruption of the permeability barrier results in an increased synthesis of cholesterol in the lower epidermis, whereas in case of chronic barrier disorders, the specific increase takes place in the upper dermis. A reduction of the cholesterol synthesis by the HMG CoA reductase inhibitor Lovastatin leads to a disturbed permeability barrier and epidermal hyperplasia. PMID- 2187312 TI - How to sell a solo practice. PMID- 2187314 TI - Ankylosing hyperostosis of the spine: case report. AB - Ankylosing hyperostosis of the spine is described as osteophytic spurs or anterior osseous bridges with thickening of the corresponding vertebral cortex. The ossification includes the ligamentum longitudinale anterius and the peripheral part of the disc. Our patient had minor complaints but at the time of consultation was symptomatic. PMID- 2187313 TI - Acute rheumatic fever: is it returning to Virginia? AB - In summary, rheumatic fever seems to be on the rise in the United States. It remains to be seen whether this case is an example of a resurgence of ARF in adults in Virginia, but it probably does, since there are a number of cases being seen in the pediatric population. PMID- 2187315 TI - How we got here: case report from the class of 1904. PMID- 2187316 TI - [How to choose a partner nowadays? A crucial question for the prevention of AIDS]. AB - This article reviews the literature on choice of partner, with the aim of stimulating though about the aids prevention. The criteria involved in choosing a partner are discussed, and a model describing the process by which a couple meet, continue to see one another, and finally decide to live together is presented. This model shows that those times and situations where individuals are most likely to put themselves at risk of contracting aids cannot be identified. This implies that the whole process of partner choice is to be considered for preventive measures. PMID- 2187317 TI - Noninvasive techniques for evaluation of heart function and hemodynamics in arterial hypertension. An overview. AB - Summarizing our experience with noninvasive techniques in arterial hypertension we can establish that a fast development is going on and noninvasive techniques are useful for functional analysis. This holds for older techniques as phonocardiography with estimation of STI and apexcardiography as well as impedance cardiography and radiocardiography. This is valid especially for newer techniques as color coded 2D-Doppler-echocardiography, radionuclideventriculography, thallium scintigraphy and magnetic resonance tomography. PMID- 2187318 TI - Cardiovascular anomalies of cephalothoracopagus synotus. A case report and review of the literature of 23 Japanese autopsied cases. AB - A case of cephalothoracopagus female twins is reported, and the anatomical and pathologic features are described in detail. The central nervous systems were completely double. However, there were three eyeballs, two on the well-formed face and one in the cranial base, forming a saddle-shaped ridge of orbital plates. The latter was supplied by optic nerves of both individuals. On the other hand, there was a single esophagus, stomach and duodenum, but the intestine was shared equally at the jejunum by the two individuals. The larynges, tracheae, lungs, hearts, livers, pancreases, spleens and urogenital organs were also duplicated. Previously unreported abnormalities of the hearts are described, and a comparison with similar autopsy cases reported previously in Japan is given. PMID- 2187319 TI - Undifferentiated carcinoma of the parotid gland in a 10-month-old child. AB - Malignant salivary gland tumors in children are very rare. This report describes the autopsy of a child with parotid gland cancer. The patient, a 10-month-old girl, was admitted to the Nagoya First Red Cross Hospital with facial nerve palsy. Incisional biopsy of a post-auricular tumor was performed, and undifferentiated carcinoma was diagnosed. The patient died 6 months later of respiratory failure due to pulmonary lymphangitis carcinomatosis. Light and electron microscopic and immunohistochemical examinations of the tumor tissue were performed. The tumor cells were arranged in a medullary, sheet-like manner. Keratinization or mucus lakes were not observed. PAS-alcian blue staining demonstrated intracytoplasmic mucus as granules, and also small intercellular droplets of mucus that might otherwise have been unnoticed. Ultrastructurally, some of the tumor cells had tonofilament-like keratin filaments, and also small hollow spaces bounded by microvilli and containing secretory particles. These were stained by antisera against CEA and keratin. These findings are suggestive of differentiation to mucoepidermoid carcinoma. We also review and discuss malignant salivary tumors of epithelial origin in children. PMID- 2187320 TI - Immunohistochemical demonstration of nonspecific cross-reacting antigen in normal and neoplastic human tissues using a monoclonal antibody. Comparison with carcinoembryonic antigen localization. AB - Nonspecific cross-reacting antigen (NCA) immunoreactivity was localized in normal and neoplastic human tissues using a monoclonal antibody to 55, 90 and 95 kDa molecules of NCA. This was compared to the localization of immunoreactive carcinoembryonic antigen (CEA) as demonstrated by polyclonal and monoclonal antibodies. In frozen sections, CEA was localized in normal surface epithelium of the stomach and colon where NCA was only weakly detected. Type 1 and type 2-like pneumocytes were positive for NCA, while CEA was localized only in type 2-like pneumocytes. CEA and NCA were both demonstrated in ductal cells of frozen pancreatobiliary and mammary tissues. The antigenicity of CEA and NCA in normal tissues was significantly lost after paraffin embedding as compared to frozen sections. NCA was consistently demonstrated in eccrine sweat glands embedded in paraffin. In various tumor tissues, CEA and NCA were colocalized and expression increased sufficiently to be detected in paraffin sections. Adenocarcinomas of the stomach and colon and cystadenocarcinoma of the pancreas, as well as neuroendocrine carcinomas of the lung and thyroid, showed a CEA predominance over NCA. In ductal adenocarcinomas of the pancreas and breast and in cholangiocarcinoma, NCA reactivity was greater than CEA. Keratinizing foci of most squamous cell carcinomas of mucosal origin and some adenocarcinomas equally expressed both. Hepatocellular carcinoma, lobular mammary carcinoma and papillary thyroid carcinoma were positive only with unabsorbed polyclonal antibody which widely recognizes CEA-related substances. Renal cell carcinoma, prostatic adenocarcinoma, transitional cell carcinoma, anaplastic carcinomas, choriocarcinoma and basal cell carcinomas showed little or no immunoreactivity. Hence the relative ratio of CEA/NCA expression in tumors was dependent on the tissue of origin and histologic type. The cytoplasmic granular staining of NCA in cancer cells was a noteworthy difference from the plasma membrane-associated localization of CEA. PMID- 2187321 TI - Overlap of concanavalin-A and insulin imprinting in rat thymocytes. AB - The thymocytic insulin binding in rats treated with the hormone neonatally on a single occasion increased considerably compared to the untreated control by 3 months of age. Treatment with Concanavalin-A also accounted for an increase in adult insulin binding, whereas neonatal treatment with insulin did not alter the binding relations of Concanavalin-A in adulthood. PMID- 2187322 TI - Permanence of the cell-to-cell transmission of insulin induced hormonal imprinting. AB - When insulin-treated (imprinted) Chang liver cell cultures were mixed with cultures which did not receive insulin treatment the information of imprinting was transmitted to the cultures which were not in direct contact with insulin. The ability of the cells to transmit imprinting was long lasting and could be detected even after four weeks, when it was nearly of the same degree as at the first measurement. Difference was found between the binding capacity of the receptors of the plasma membrane and those of the nuclear membrane. PMID- 2187323 TI - A perspective on fluoride and the treatment of osteoporosis. PMID- 2187324 TI - Fluoride in the prevention of osteoporosis and fractures. AB - Age-related fractures, especially hip fractures, produce sufficient morbidity and mortality to make osteoporosis a disease worth preventing, and accurate techniques exist to identify groups at high risk of fracture by virtue of low bone mass. While the need for prevention is evident, no specific program of fluoride use for this purpose has been devised, and epidemiologic data provide little support for the notion that exposure to fluoride reduces hip fracture incidence. At present, fluoride cannot be recommended as a prophylactic agent for the fractures that are the primary adverse health outcome of osteoporosis. PMID- 2187325 TI - Fluoride effects on bone crystals. AB - Fluoride is known to have biological effects on bone cells as well as physicochemical effects on bone crystals. This review concentrates on the latter. Fluoride increases the stability of the apatite lattice and decreases the solubility of the apatite crystals. In bone mineral, this ion has been shown to affect bone crystal structure by increasing crystallinity and reducing specific surface area. These changes in turn lead to changes in the chemistry of bone mineral. Bone mineral deposition is delayed by fluoride. This ion does not diffuse into bone already formed, but is incorporated during mineralization. Subsequently fluoride tends to accumulate in the most highly mineralized bone. Bone treated with fluoride has been shown to be more resistant to acid dissolution than normal bone, which would explain the reduced rate of resorption of fluoridated bone. The distribution of fluoride in bone is not uniform, but its net effect is to increase bone mineral density probably by an increased packing of bone crystals. Finally, there is a debate as to whether fluoride produces a bone of different quality. Whether these changes in the quality of bone will prove to be helpful or harmful remain to be determined. PMID- 2187326 TI - Effects of fluoride treatment on bone strength. AB - Bone mass and architecture in appendicular and most axial sites is controlled primarily by the tissue-loading history. We introduce a conceptual framework for understanding how fluoride treatment alters this control and can cause systemic increases in bone mass. Due to possible adverse influences of fluoride on the mineralized tissue physical characteristics, however, the increase in bone mass does not necessarily result in an increase in bone strength. Using engineering analyses of bone trabeculae, we calculate the losses in trabecular strength which can be caused by the presence of hypomineralized or hypermineralized fluorotic tissue. Significant increases in bone volume fraction and bone mass may be required to overcome these strength deficits. PMID- 2187327 TI - Treatment of the vertebral crush fracture syndrome with enteric-coated sodium fluoride tablets and calcium supplements. AB - A cohort of 101 patients were treated with enteric-coated sodium fluoride tablets and calcium supplements. Vitamin D was also given in supra-physiologic doses in 70% of the cases. Lumbar bone mineral density (BMD), as measured by dual-photon absorptiometry, increased in a linear fashion up to four years, irrespective of the value of initial BMD and of the underlying condition, be it involutional osteoporosis (the vast majority), glucocorticoid osteoporosis, or even osteogenesis imperfecta. Estrogen replacement therapy (ERT) seemed to promote the fluoride-induced increase in lumbar BMD, as did the vitamin D supplements. Of these patients, 17% proved "resistant" to the therapy. There was no way of predicting who would be in this category. Compared with an age- and sex-matched control group, women showed significantly different behavior of their bone mass. In the control group, the losses were highly significant at the lumbar spine and at all three scanning sites of the forearm, as measured by single-photon absorptiometry. In contrast, the fluoride group had a significant gain of BMD at the lumbar spine and changes of BMC at the forearm were not significant. Fluoride thus preserved bone mass at the appendicular skeleton, while increasing it at the axial skeleton. When comparing the patients who received vitamin D supplements and those who did not, there was a significant difference in the appendicular skeleton. The distal forearm in the vitamin D-supplemented group tended to gain, whereas the midforearm lost significant bone mass. The trend was reversed in the group without vitamin D-supplementation, a more favorable pattern. Therefore, vitamin D supplements should not, as a rule, be provided to such patients. The biochemical hallmark of the fluoride-induced changes is a slight rise of the alkaline phosphatase within the normal range. Alkaline phosphatase levels that exceed the upper limit of normal signal a warning that too much fluoride and/or too little calcium supplements are being administered, or that a fluoride-related complication is impending or has occurred (e.g., a stress fracture). Osteosclerosis was achieved in 69% of the cases who had a radiological followup of at least four years (average period of appearance: 1.8 years). Stress fractures in the lower limbs occurred in 17 patients, almost exclusively in females, and appeared on average 2.2 years after initiation of therapy. In this group of stress fractures there was significant cortical bone loss at midforearm.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2187328 TI - Bone effects of fluoride in animal models in vivo. A review and a recent study. AB - The effects of fluoride on bone in various animal models are reviewed. In these studies, the doses of fluoride varied from those equivalent to therapeutic doses to toxic doses, and the duration of the treatment was from 15 days to 33 months. No significant modification in serum calcium, phosphorus, and alkaline phosphatase was reported. An increased serum osteocalcin level was noted in ewes. Evidence for hyperparathyroidism was found in some but not all animal models. Studies performed in the rat reported that fluoride had different effects on the periosteal and endosteal bone. An increase in the extent of eroded surfaces was observed in all experimental studies, except one in the mouse. Increases in osteoid parameters and in the number of osteoblasts were noted in mouse, cat, pig, and ewe. Only one study, carried out in dogs, mentioned a decrease in osteoid parameters. Most of the authors reported a mineralization defect due either to a modification in the composition of the bone matrix or to a low calcium intake. The formation period was augmented during fluoride treatment but, at a fluoride dose equivalent to therapeutic doses, this augmentation was mainly due to an increased active formation period. In contrast, at a fivefold greater dose, it was due to an increased inactive formation period. The augmentation of bone volume after fluoride treatment was attributed to an unbalanced coupling between resorption and formation in favor of formation. All these experimental studies support the conclusion that fluoride induces a stimulation of the birthrate of osteoblasts, but at high doses decreases their activity. PMID- 2187329 TI - [Tuberculous microbladder. Ileocystoplasty for enlargement]. AB - We have had occasion to treat 8 patients suffering from tuberculous microbladder on whom we carried out augmentation plasty with a segment of ileum according to Ring-plasty technique in 6 cases, and with U-morphology in the other two, all displayed as the main symptom increase in mictional frequency. Six patients were subjected to prior tuberculostatic treatment. Mictional frequency improved in all patients. We observed morphological improvement in seven patients and functional improvement in four, there was one death, in a patients who had only been having prior tubculostatic treatment for one month. Daytime continence was achieved in al cases and there was nocturnal incontinence in five patients. U or ring ileocystoplasties are simple fast techniques displaying good capacity with low pressures and residua of less than 80 cc. No vesicourethral reflux was observed when we carried out the reimplantation. PMID- 2187330 TI - [Primary adenocarcinoma of the bladder as single tumor. Study of 7 cases and review of the literature]. AB - Primary vesical adenocarcinoma is an extremely uncommon tumour, representing 0.5 to 2% of all the urothelial vesical neoplasias. Its behaviour is aggressive and its prognosis poor, especially in the seal ring cell variety. We present our experience in seven cases of vesical adenocarcinoma: one of urachal origin, two of the seal ring cell type, and four of the urothelial type with no other specificity. All were advanced stage tumours at diagnosis. There is no unified therapeutic strategy, and poor results were obtained with the various treatments used. Survival eight months after diagnosis was 42.8%. Longest survival is 15 months, corresponding to the adenocarcinoma of urachal origin. PMID- 2187331 TI - [Angiomyolipoma of the kidney with lymphatic involvement]. AB - We present a case of renal angiomyolipoma associated with tuberous sclerosis affecting the regional lymphatic ganglia. We analyse the possible etiopathogenesis of this affection and conclude, like most authors, that it may reflect the multifocalization of this tumour rather than malignity or metastatic lesion. PMID- 2187332 TI - [Urologic complication during total hip replacement. Apropos of a case and review of the literature]. AB - The authors present a case of vesical lesion during the recovery of a total loose hip prosthesis, without any type of endopelvic instrumentation being carried out. They show the cause of the perforation and warn against this type of complication in the above-mentioned surgery. PMID- 2187333 TI - [Leydig's cell tumor with endocrine syndrome: presentation of a case and review of the literature]. AB - We present a case of Leydig's cell tumour in a young adult, with endocrinal manifestation. The relative rarity of these neoplasias. The opposition of their clinical manifestations, virilizing in the child and feminizing in the adult. Its always benign evolution in infancy and its occasional malignity in the adult (20%) are commented on and reviewed. PMID- 2187334 TI - Subtle and atypical cobalamin deficiency states. AB - Evidence for cobalamin (vitamin B12) deficiency usually involves some combination of low serum cobalamin levels, clinical abnormalities (classically, megaloblastic anemia and neurologic defects), metabolic abnormalities, and response to therapy. However, cobalamin deficiency may often display few of the expected clinical findings. Identification of the underlying cause is also important in the diagnosis of deficiency, and its value may be particularly great when the expression of deficiency is subtle. The cause of cobalamin deficiency is usually malabsorptive, but may sometimes be limited to malabsorption of food cobalamin while free cobalamin is absorbed normally. Nongastroenterologic entities may sometimes also be found. All of these considerations allow the proposal of four patterns of cobalamin deficiency. The first type is classical deficiency; typical megaloblastic anemia with or without neurologic dysfunction occurs because of classical cobalamin malabsorption such as lack of intrinsic factor (pernicious anemia). The second type consists of classical cobalamin malabsorption in which the cobalamin deficiency is expressed subtly rather than in classical fashion. There is no megaloblastic anemia and sometimes the only evidence of deficiency may be metabolic. In the third type, cobalamin deficiency is expressed classically but is attributable to a subtle or atypical cause, such as food cobalamin malabsorption. In the fourth type, deficiency is both expressed subtly and arises from subtle or atypical causes. Such presentations require further investigation but are a challenging expansion of our understanding and recognition of cobalamin deficiency. PMID- 2187335 TI - Anti-leukemic potential of methyl-cobalamin inactivation by nitrous oxide. AB - Myelo-cytotoxicity of extended nitrous oxide (N2O) inhalation was described almost forty years ago and then incidentally applied already with temporary success for suppressing leukemia. In 1948 the accompanying megaloblastic maturation arrest was explained by inactivation of the methylcobalamin coenzyme and subsequent folate deficiency. We studied the anti-leukemic effect of N2O on a transplantable acute leukemia in B(rown) N(orway) rats. Progression of this B,N,M(yelocytic)L(eukemia) was measured as spleen and liver weights, and leukemic blood cell counts. The deoxyuridine (dU)-suppression test provided in vitro indication of the functional folate activity of leukemic cells. Breathing of N2O oxygen considerably reduced but did not eradicate, BNML-proliferation. Addition of anti-metabolites, interfering with some enzyme in the folate metabolism beyond the methylcobalamin co-enzyme dependent methionine synthase step, acted at least synergistically. The anti-leukemic effect of cycloleucine, which reduces S adenosyl-methionine synthesis by inactivation of methionine adenosyltransferase, was moderate but became much stronger with N2O inhalation. Methotrexate, a potent anti-leukemic agent by inhibiting tetrahydrofolate (THF) generation through inactivation of di-HF reductase, became highly anti-BNML, even in low dosage when combined with or preceded by N2O. 5-Fluorouracil, which inhibits methylene-THF dependent thymidilate synthase, itself was surprisingly anti-BNML, but also became much more potent with previous or concomitant N2O exposure. Preliminary dU suppression test results with human acute leukemia cells, exposed to N2O and/or folate antagonists in vitro, correlated well with the in vivo BNML-experiments. Combining the anticobalamin activity of N2O with an anti-folate therefore seems to be a promising chemotherapeutic approach. PMID- 2187336 TI - Application of the avidin-biotin-peroxidase complex technique for ultraimmunocytochemical characterization of leukemic cells. AB - For simultaneous demonstration of cellular ultrastructure, myeloperoxidase activity, and presence of a membrane-bound antigen in a given blood cell, we examined three different fixatives: periodate-lysine-paraformaldehyde (PLP) and paraformaldehyde and glutaraldehyde for their applicability to preembedding electron microscopic immunocytochemistry using monoclonal antibodies and the avidin-biotin-peroxidase complex (ABC) technique. This procedure was examined in samples from 3 normal volunteers and 29 patients with acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), lymphosarcoma cell leukemia (LSCL), blastic phase of chronic myelogenous leukemia (CML-BC), or other unclassified leukemias. PLP fixation preserved the immunoreactivity of surface glycoproteins as well as immunoglobulins to the most satisfactory extent. Leukemic cells fixed with PLP maintained their fine structural details, so that we could identify their cytoplasmic organelles, although glutaraldehyde produced the best preservation of cellular ultrastructure. In three patients with ALL, our method revealed that a significant portion of blasts possessed both lymphoid surface antigens and peroxidase-positive cytoplasmic granules. Our method was also useful in identifying the lineage of peroxidase-negative leukemic cells, including monoblastic leukemia and megakaryoblastic leukemia cells. Ultraimmunocytochemistry using PLP fixation and the ABC technique may be a promising strategy for determining the nature of blastic cells that remain unclear after a conventional work-up, for characterizing leukemic cells in patients with a relatively low blast cell count in the bone marrow or peripheral blood, and for estimating the presence and frequency of leukemia with multilineage expression. PMID- 2187338 TI - New frontiers in vitamin B12 metabolism. A symposium in honor of Robert F. Schilling. Madison, Wisconsin. October 6, 1989. Proceedings. PMID- 2187337 TI - Structure of the granulocyte macrophage colony-stimulating factor gene in patients with the myelodysplastic syndromes. AB - DNA samples from 76 patients with the myelodysplastic syndromes, including 10 cases with a partial deletion of the long arm of chromosome 5 (5q-), were examined for structural rearrangements of the granulocyte/macrophage colony stimulating factor (GM-CSF) gene. No abnormalities were detected, indicating that structural aberrations of this gene are not a feature of the myelodysplastic syndromes. PMID- 2187339 TI - Robert F. Schilling--a tribute. PMID- 2187340 TI - Cobalamin as coenzyme: a twisting trail of research. AB - Cobalamin derivatives serve as coenzymes for the body's two cobalamin-dependent enzymes--adenosylcobalamin-dependent methylmalonyl CoA mutase, and methylcobalamin-dependent methionine methyltransferase. This essay reviews, in brief form and in personal terms, the history, beginning in the mid-1950s, of how these enzymes and coenzymes were discovered and what has been learned of their reaction mechanisms. It is clear that because of the fragility of the unique carbon-cobalt bond in cobalamin coenzymes, they serve primarily as free radical formers. This accounts for their efficiency in abstracting hydrogen from substrate molecules and for a subsequent chain of events that results in the isomerization of methylmalonyl CoA, the transfer of methyl groups, and (in certain bacteria) the reduction of ribonucleotides. Some thoughts are offered on the possible evolutionary significance of these facts. PMID- 2187342 TI - Mapping dysmorphic syndromes with the aid of the human/mouse homology map. PMID- 2187341 TI - Genomic imprinting: review and relevance to human diseases. PMID- 2187343 TI - Pulmonary host defenses and oropharyngeal pathogens. AB - The lower respiratory tract is repetitively inoculated with oropharyngeal bacteria and yet pneumonia is an infrequent event. Efficient mechanisms of antibacterial defense are present in the respiratory tract that eliminate microbes before their presence or multiplication leads to disease in the majority of instances. Resident pulmonary defenses consist of aerodynamic defenses, the mucociliary apparatus, alveolar macrophages, complement, and surfactant. These resident defenses can be augmented by the development of an inflammatory response or the development of specific immunity. Significant species variability exists in the efficiency and mechanisms of clearance for oropharyngeal organisms. Streptococci are cleared promptly, Branhamella catarrhalis is cleared slowly, whereas non-typable Haemophilus influenzae multiply before being cleared. A dual phagocytic system of alveolar macrophages and recruited polymorphonuclear leukocytes is required for clearance of most oropharyngeal microbes. Systemic immunization can significantly enhance clearance of non-typable H. influenzae, suggesting immunoprophylaxis might be possible for this organism. PMID- 2187344 TI - A prospective randomized study of saline solution amnioinfusion. AB - We performed a prospective randomized study of saline solution amnioinfusion in four types of pregnancy complications: postterm pregnancy, variable decelerations in labor, preterm labor, and oligohydramnios-suspected growth retardation. A total of 100 patients were randomized, 43 to undergo amnioinfusion and 57 to be in a control group. Patients undergoing amnioinfusion had a significantly decreased incidence of postpartum endometritis (2.4% vs 19%, p = 0.01) and a lower incidence of cesarean delivery that was due to fetal distress in labor (4.7% vs 16%, p = 0.07). The use of amnioinfusion also made a significant contribution to the four-quadrant ultrasonographic estimate of amniotic fluid volume (14.7 vs 9.8 cm, p less than 0.001). All other maternal and neonatal outcome parameters were similar between the two groups. We conclude that saline solution amnioinfusion in labor may be a beneficial procedure but that further studies are needed. PMID- 2187345 TI - Increasing quantity of maternal immunoglobulin G in trophoblastic tissue before the onset of normal labor. AB - While levels of maternal immunoglobulin G (IgG) increase in the fetal circulation during the third trimester, actual trophoblastic concentrations have not been extensively studied. To investigate this process, placentas from 71 patients with gestational ages between 26 and 42 weeks were examined by means of a peroxidase antiperoxidase immunostaining technique specific for IgG. Linear regression revealed a significant increase in antibody with advancing gestational age (r = 0.36, p less than 0.01). In addition, placentas from patients in spontaneous term labor revealed a significantly higher antibody level when compared with those of patients at term delivered electively before the onset of labor (mean +/- SEM 2.6 +/- 0.2 vs 1.7 +/- 0.3, p less than 0.02). Patients in premature labor failed to demonstrate this increase in antibody staining. One possible explanation for these findings is an enhanced recognition of the fetal trophoblastic tissue by the maternal immune system at term. It also suggests immunologic factors may play an important role in the initiation of normal labor. PMID- 2187346 TI - Aneurysm of the vein of Galen: a new cause for Ballantyne syndrome. AB - Ballantyne syndrome is a condition of multiple causes and is characterized by maternal, placental, and fetal edema. We describe the first case of Ballantyne syndrome in a patient whose fetus had ultrasonographic demonstration of an aneurysm of Galen's vein. PMID- 2187347 TI - The amniotic fluid index in normal human pregnancy. AB - The four-quadrant sum of amniotic fluid pockets (amniotic fluid index) was studied prospectively in 791 normal pregnancies. Interobserver and intraobserver variation was 3.1% and 6.7%, respectively. Logarithmic transformations were used to establish the mean and 90% confidence intervals for the amniotic fluid index at each week of gestation. In term pregnancies, the boundaries of the amniotic fluid index were 115 mm (mean), 68 to 196 mm (5th to 95th percentiles). In postdates pregnancies greater than 42 weeks, the values were 108 mm (mean), 67 to 174 mm (5th to 95th percentiles), p less than 0.0001. However, the values for each week were statistically distinct, indicating the need to reference amniotic fluid index measurements to week-specific normative tables for accurate interpretation. This study provides normative data for the amniotic fluid index throughout pregnancy. PMID- 2187348 TI - Serum fructosamine and amniotic fluid insulin levels in patients with gestational diabetes and healthy control subjects. AB - Gestational diabetic pregnancies with fetal hyperinsulinism should be identified because these cases require insulin therapy. To determine the relationship between the serum fructosamine and amniotic fluid insulin concentrations, these substances were measured in 87 pregnant women with impaired glucose tolerance. Fructosamine was also measured in 678 healthy pregnant control subjects, in 113 of whom amniotic fluid insulin levels were available. Fetal hyperinsulinism was rare at serum fructosamine levels of less than 2.6 mmol/L. These results suggest that when both the oral glucose tolerance test and fructosamine level are used, only 30% of women with gestational diabetes need to undergo amniocentesis to assess fetal insulin homeostasis. PMID- 2187349 TI - Benefits of placental biopsies for rapid karyotyping in the second and third trimesters (late chorionic villus sampling) in high-risk pregnancies. AB - In a total of 301 placental biopsies in the second and third trimesters, 225 were performed because of suspicious ultrasonographic findings. In this group there was a high rate of aneuploidies (20%). As opposed to the alternative methods for rapid karyotyping, placental biopsies can easily be performed even in pregnancies with abnormal amounts of amniotic fluid. Oligohydramnios and polyhydramnios were key ultrasonographic findings in 38% of cases and were found to be associated with 22% of abnormal chromosomal findings. Suggestive ultrasonographic findings seem to justify the exclusive use of direct preparation. PMID- 2187350 TI - Flow velocity waveforms in uterine and umbilical arteries during the angiotensin II sensitivity test. AB - The angiotensin II sensitivity test has been used to predict the development of hypertension during pregnancy. We investigated the systolic/diastolic ratios of flow velocity waveforms in the uterine and umbilical arteries by means of a color Doppler system in 15 healthy women at 24 to 26 weeks' gestation. A significant increase (p less than 0.001) was observed in the systolic/diastolic ratio in the uterine artery, which was unaffected by the location of the placenta. In five women a differential effect of angiotensin II on the systemic diastolic blood pressure and on the systolic/diastolic was observed: the uterine circulation appeared to have a slower response and a faster recovery than the diastolic blood pressure. No changes in the systolic/diastolic ratio in the umbilical artery were observed. PMID- 2187351 TI - The relationship between the umbilical artery systolic/diastolic ratio and umbilical blood gas measurements in specimens obtained by cordocentesis. AB - The purpose of this investigation was to prospectively determine the relationship between the umbilical artery systolic/diastolic ratio and the umbilical blood gases in samples obtained from 165 fetuses during diagnostic cordocenteses. In each instance the sample was the umbilical vein. The systolic/diastolic ratio was measured in a midsection of the umbilical cord. Analyses used stepwise, multiple linear regression. The mean +/- SEM gestation was 29 +/- 0.4 weeks; 72% of fetuses were greater than or equal to 25 weeks and were considered potentially viable. There was no relationship between the umbilical artery systolic/diastolic ratio and pH, PCO2, or PO2 in fetuses either less than 25 weeks' gestation or greater than or equal to 25 weeks' gestation but with systolic/diastolic ratios greater than or equal to the 95th percentile for control fetuses at 25 weeks' gestation with normal blood gas values (3.5). In fetuses greater than or equal to 25 weeks' gestation with systolic/diastolic ratios that exceeded 3.5 (n = 37), there was a strong relationship between the systolic/diastolic ratio and the umbilical venous PO2 (r = -0.68, p less than 0.0001), which was independent of gestational age. Each fetus with repetitively absent-reversed umbilical artery diastolic blood flow and a heart rate greater than 90 beats/min (n = 6) had blood gas measurements consistent with hypoxia and acidosis. This investigation suggests that factors that lead to an increase in the umbilical artery systolic/diastolic ratio are associated with a progressive impairment of placental gas exchange and that by the time diastolic flow is lost, hypoxemia is present. PMID- 2187352 TI - Maternal indomethacin therapy in the treatment of polyhydramnios. AB - Fifteen patients with polyhydramnios and clinical symptoms related to excess amniotic fluid volume were treated with indomethacin therapy that was started at a mean gestational age of 27.4 +/- 2.79 weeks and discontinued at a mean gestational age of 32.9 +/- 1.83 weeks. Patients were treated with 2.0 to 2.2 mg of indomethacin per kilogram of body weight per day, either orally or by rectal suppositories. No therapy was administered after 35 weeks, and the duration of therapy was no longer than 4 weeks. The majority of fluid reduction occurred within the first week of treatment. Subsequently, a smaller but steady reduction of fluid was observed. All patients were delivered after 38 weeks with a mean birth weight of 3543 +/- 586.3 gm. Examinations of newborns at birth and follow up at 3 months, 6 months, and 1 year revealed no adverse effects of indomethacin administration. PMID- 2187353 TI - Antenatal origin of neurologic damage in newborn infants. II. Multiple gestations. AB - Necrosis of the cerebral white matter may be identified in living infants with echoencephalography. Echoencephalographic studies were performed in 89 twins and 12 triplets at less than 36 weeks of gestation to determine the incidence and complications associated with antenatal necrosis of the cerebral white matter. Antenatal necrosis of the cerebral white matter was identified when brain atrophy or cavities in the white matter were present by day 3 of life. Fourteen infants (13.8%) were considered to have antenatal necrosis of the cerebral white matter. The incidence of antenatal necrosis of the cerebral white matter was higher in monochorionic than in dichorionic infants (30% vs 3.3%; p less than 0.001). Univariate analysis showed that antenatal necrosis of the cerebral white matter was significantly associated with polyhydramnios, intrauterine fetal death of the cotwin, hydrops, multiple placental vascular connections, and placental artery-to artery, vein-to-vein, and artery-to-vein anastomosis. Logistic regression analysis showed that antenatal necrosis of the cerebral white matter was predicted by the presence of either artery-to-artery or vein-to-vein anastomosis and by intrauterine fetal death of a cotwin. Vein-to-vein anastomosis had the strongest association, because 89% of seven infants with vein-to-vein anastomosis demonstrated antenatal necrosis of the cerebral white matter (p = 0.003). Monochorionic multiple gestations frequently are complicated by antenatal necrosis of the cerebral white matter. Multiple vascular connections with vein-to vein anastomosis appear as the most important associated factor for antenatal necrosis of the cerebral white matter in this population. PMID- 2187354 TI - Fetal intervention in obstructive uropathy: prognostic indicators and efficacy of intervention. AB - Management of the fetus with bilateral hydronephrosis is controversial; ability to predict outcome and efficacy of prenatal intervention are unknown. We studied 40 fetuses referred for ultrasonography, examination of fetal urine, and possible therapy. We retrospectively assigned fetuses to a good prognosis group if fetal urine was hypotonic (sodium less than 100 mEq/L, chloride less than 90 mEq/L, osmolarity less than 210 mOsm/L) and there was no ultrasonographic evidence of dysplasia; we assigned fetuses to a poor prognosis group if even one criterion was abnormal. Survival was greater in the good prognosis group than in the poor prognosis group (81% vs 12.5%; 87% vs 30%, excluding abortions) (p less than 0.005). We then attempted to assess the efficacy of prenatal urinary decompression by comparing outcome within the good and poor prognosis groups. Survival with intervention was greater in both the good prognosis group and the poor prognosis group (89% vs 70% and 30% vs 0%). In 6 of the 8 survivors in the good prognosis group, severe oligohydramnios was reversed by decompression. We conclude the fetal urine electrolyte levels and ultrasonographic appear helpful in predicting residual fetal renal function and neonatal outcome and that prenatal decompression may prevent the development of fatal pulmonary hypoplasia. PMID- 2187355 TI - Intrafetal prostaglandin F2 alpha administration for midtrimester pregnancy termination: a case report. AB - An original route for prostaglandin F2 alpha administration for midtrimester pregnancy termination is presented. The diagnosis of nuchal cystic hygroma in a hydropic fetus with severe oligohydramnios was made by real-time ultrasonography. Forty milliliters of fluid was aspirated for laboratory studies and prostaglandin F2 alpha was injected into the nuchal cysts to induce abortion. The pregnancy was successfully terminated 8 hours later. PMID- 2187356 TI - Pneumatometra. AB - We report a patient who had a significant amount of gas distending the uterine cavity. Severe cervical stenosis was noted at the time that curettage was performed. Because of the cervical stenosis, gas was trapped within the endometrial cavity. PMID- 2187357 TI - Immunocytochemical localization and messenger ribonucleic acid concentrations for human placental lactogen in amnion, chorion, decidua, and placenta. AB - Human placental lactogen is one of the major hormones secreted by the placental syncytiotrophoblast and detected in the maternal circulation. Other sources of this hormone in intrauterine tissues at term have been sought by means of immunohistochemistry and northern analysis. Avidin-biotin immunoperoxidase staining with a specific polyclonal antibody to human placental lactogen showed this hormone to be present in groups of cells at the interface between chorionic cytotrophoblast and decidua parietalis and in some cells of the basal plate in addition to the classic source, the syncytiotrophoblast. Hybridization of polyadenylic-(+)ribonucleic acid extracted from amnion, chorion, decidua parietalis, basal plate, and placental trophoblast with a radiolabeled 48 mer oligonucleotide and a 540 base pair complementary deoxyribonucleic acid probe to human placental lactogen showed the placental trophoblast to be the major source of human placental lactogen and the extravillous chorion and basal plate to be additional minor sources. PMID- 2187358 TI - Fructosamine assay as screening test for gestational diabetes. PMID- 2187359 TI - Hydramnios in the third trimester of pregnancy: a change in the distribution of accompanying fetal anomalies as a result of early ultrasonographic prenatal diagnosis. PMID- 2187360 TI - Fetal Doppler ultrasonography and cordocentesis. PMID- 2187361 TI - Mathematic form corrected. PMID- 2187362 TI - Is obstetric progress dependent on rigorous randomized controlled trials? PMID- 2187363 TI - Cervical length may change during ultrasonographic examination. PMID- 2187364 TI - Genetic diversity of Plasmodium falciparum shows geographical variation. AB - Sixty Plasmodium falciparum isolates, 20 each from Thailand, Zimbabwe, and Brazil, were characterized for 20 variant genetic markers, including the enzymes glucose phosphate isomerase, adenosine deaminase and peptidase, 11 other proteins detected by 2-dimensional electrophoresis (2D-PAGE), 2 merozoite surface antigens (MSA-1 and MSA-2), one exported antigen (Exp-1), and sensitivity to the drugs chloroquine, pyrimethamine, and mefloquine. The study examines the extent of diversity between individual isolates and the differences in the frequency of certain variants of the markers between the 3 countries. The principal conclusions to be drawn from the study are that there is extensive polymorphism in many of the genetically determined characters of this parasite, multiple infections with greater than 1 genetically distinct parasite are common, and there are geographical variations in the frequencies with which variant forms of certain markers occur. PMID- 2187365 TI - Susceptibility of Anopheles hermsi to Plasmodium vivax. AB - Two outbreaks of Plasmodium vivax malaria have occurred recently in southern California, and Anopheles hermsi, a newly described species closely related to A freeborni, has been implicated as the vector. To assess the competence of A. hermsi as a vector, its susceptibility to P. vivax was compared with that of the efficient vector A. freeborni by allowing 150 females of each species to feed to repletion on infected squirrel monkeys. Oocyst density was greater in A. hermsi than in A. freeborni, and the frequency and density of sporozoites were similar. A. hermsi was susceptible to P. vivax and readily supported development to the sporozoite stage. PMID- 2187366 TI - Production of a specific monoclonal antibody for the identification of Leishmania (Leishmania) venezuelensis. AB - We describe a monoclonal antibody (Mab), V1, specific for Leishmania (Leishmania) venezuelensis. Previous Mabs and DNA probes were not specific for this parasite, and so it was not directly possible to distinguish L. (L.) venezuelensis from other Leishmania species. Immunofluorescent staining using Mabs may be performed on very few parasites, whereas other methods of identification usually require far greater numbers of organisms. L. (L.) venezuelensis frequently dies on subculture. Mab V1 can be used to identify this parasite by indirect immunofluorescence and radioimmunoassay. PMID- 2187368 TI - [Current aspects of the use of ultrasonic screening in gynecology]. PMID- 2187367 TI - Occurrence, characteristics, and patterns of HIV-1 and HIV-2 western blot indeterminate sera in low risk populations in West Virginia and pre-AIDS Africa. AB - To further characterize HIV-1 and HIV-2 Western blot indeterminate (IWB) sera, 402 sera from 318 healthy low-risk individuals from West Virginia and 159 African sera obtained in the pre-AIDS era (1968-1972) were studied. All IWB sera tested for antigen by HIV-1 enzyme immunoassay (EIA-Ag) were negative. HIV-1 and HIV-2 IWB reactivity occurred independent of HIV-1 and HIV-2 false-positive testing for antibody by enzyme immunoassay (EIA-Ab) and no cross-reactions between HIV-1 and HIV-2 IWB patterns were detected. The IWB patterns were reproducible, demonstrated no age or sex related pattern, and showed no evidence of vertical or horizontal transmission. The African sera exhibited a significantly higher number of IWB patterns. IWB reactivity in HIV-1 and HIV-2 seronegative individuals may not be viral in origin and the occurrence of IWB pattern may vary among populations. PMID- 2187369 TI - [Clinico-enzymologic parallels in patients of reproductive age with benign epithelial ovarian tumors]. AB - Proteolytic enzymes and their inhibitors have been assayed in sera of 120 patients with benign epithelial ovarian tumors during preoperative menstrual cycles and in 3 years following surgery. The patients showed imbalances in protease inhibitors which failed to be improved by the operative treatment in a proportion of patients. Follow-up of this patient population is recommendable. A serum elastase test was proposed to predict benign epithelial ovarian tumors. PMID- 2187370 TI - [Serologic indicators of Chlamydia infection in infertile women]. PMID- 2187371 TI - [Long-term antidepressive medication-- an increased anesthetic risk?]. AB - Antidepressants inhibit the re-uptake of norepinephrine at the monoaminergic synapse from the synaptic fissure, leading in this way to an increased sensitivity to catecholamines. In addition, antidepressants have alpha1-, H1- and H2-receptor blocking effects and also anticholinergic effects; the tricyclic antidepressants in particular are known for these properties. A few animal experiments and some case reports indicate that a long-term treatment with these substances can lead to intra-operative blood pressure fluctuations, tachycardia and arrhythmias. Therefore a number of authors recommend that antidepressants be withdrawn 3 days before a planned operation. In view of the pharmacokinetics of these substances and the long-term adapting processes at the monoaminergic synapse this period is certainly too short to achieve complete loss of effectiveness. Other authors think preoperative withdrawal is not indicated if there is careful intraoperative monitoring. We agree with the latter opinion. Inhalation anesthesia with isoflurane or enflurane should be preferred. The muscle relaxant pancuronium should not be used, and exogenous intake of catecholamines should be avoided. Opiates seem to have a positive effect on cardiac stability. Benzodiazepines show the least interactions with antidepressants and are therefore recommended for premedication. In the postoperative period the possibility of an anticholinergic syndrome has to be considered. PMID- 2187372 TI - [Nalbuphine and piritramid in the postoperative phase in young children. 1. General condition]. AB - The influence of piritramide and nalbuphine versus placebo on the postoperative comfort of 54 children of ASA-group I and II in the age between 1 and 4 years was tested in a randomized double blind trial using the comfort/discomfort scale according to Buttner et al. METHODS. Operations, premedication and anesthesia were standardized. The patients were premedicated with midazolam 0.5 mg/kg rectally and a subsequent i.m. injection of ketamine 2.0 mg/kg with atropine 0.01 mg/kg. Anesthesia was induced and maintained by inhalation of oxygen/nitrous oxide and halothane (FiO2 = 0.3). All children were intubated and ventilation was controlled during the operation. After the operation, while in steady-state anesthesia with 0.5 vol% halothane and during spontaneous respiration the children received either piritramide (n = 17) or nalbuphine (n = 20) at a dose of 0.1 mg/kg, or placebo (n = 17) i.v. Respiratory and circulatory parameters were recorded for 15 min before the end of anesthesia. At 5 min after halothane had been discontinued the first measurement of the children's behavior was started, with 4 subsequent measurements at fixed time intervals of 15 min. The measuring system included the following 6 scaled items: wake-up reaction, methodical defense against stimuli, crying, facial expression, posture of the torso, posture of the legs. In addition, the waking state was scored at the same time intervals as awake, arousable, or not arousable. During the 1-h observation period all children who seemed to feel uncomfortable received midazolam i.v. at a maximal dose of 2 mg. Up to 24 h the required supplemental analgesics were noted, as were episodes of psychomotor agitation and vomiting. Written consent was obtained from the ethical committee and the children's parents. The results were tested in a 2 factorial analysis of variance (treatment factor: drugs; within-subject factor; repeated measurements). RESULTS. The 3 groups were considered to be comparable in terms of age, body weight, kind and duration of operation and circulatory values. The use of supplementary analgesics showed a significant effect in the treatment factor and in the within-subject factor: during the 1-h observation period the placebo group received midazolam significantly more often (64.7%) than the piritramide group (5.9%) or the nalbuphine group (35%). During the following 7 h 29.4% of the children of the placebo group required supplementary analgesics (piritramide: 23.5%; nalbuphine: 20%). Subsequently up to the 24th postoperative hour there was no need for any analgesic in the placebo group, whereas 11.8% of the piritramide group and 15% of the nalbuphine group required analgesics.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2187373 TI - [Transcranial Doppler sonography during pulsatile and non-pulsatile extracorporeal circulation]. AB - Transcranial Doppler sonography (TCD) was used to determine the mean blood flow velocity of the middle cerebral artery (Vm-MCA) and pulsatility (systolic/diastolic flow velocity = S/D) in 25 patients undergoing aortocoronary bypass grafting before, during, and after extracorporeal circulation (ECC). Preoperatively, none of the patients had signs or symptoms of cerebrovascular disease. ECC was performed with 2.4 l/min per m2 under mild hypothermia (34 degrees C) using membrane oxygenators. After 20 min of nonpulsatile perfusion, ECC was switched to the pulsatile mode for 20 min. Nonpulsatile perfusion was applied for the remaining ECC period. Vm-MCA, S/D, mean arterial blood pressure (MABP), and nasopharyngeal temperature (T.np) were recorded continuously throughout the operation. Hematocrit and paCO2 were determined before, during, and after ECC. Following hemodilution after the introduction of ECC, Vm-MCA was significantly increased compared with the baseline values before ECC. With hematocrit and paCO2 varying insignificantly during ECC, the onset of pulsatile ECC decreased Vm-MCA and MABP simultaneously. After the re-establishment of nonpulsatile ECC, both Vm-MCA and MABP increased again. However, a linear relationship between the two variables could not be documented statistically. During pulsatile ECC, pulsatility (S/D) of the obtained TCD wave forms did not reach baseline values. In 4 cases, TCD showed cessation of diastolic blood flow velocity after induction of ECC or onset of pulsatile ECC. An increase in MABP or changes in ECC regimen promptly restored diastolic TCD signals in these cases. Our results support the concept of increased cerebral blood flow under mild hypothermic ECC. Compared with the nonpulsatile perfusion mode, we found Vm-MCA reduced during pulsatile ECC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2187374 TI - Specific enzymatic assay for D-glucarate in human serum. AB - A sensitive and specific spectrophotometric assay was developed to determine levels of D-glucarate in human serum. This assay makes use of the Escherichia coli glucarate catabolic enzymes D-glucarate dehydrase, alpha-keto-beta-deoxy-D glucarate aldolase, and tartronate semialdehyde (TSA) reductase, to convert D glucarate to equimolar quantities of pyruvate and TSA. In a one-tube reaction that included NADH, lactate dehydrogenase, and the three E. coli enzymes, 1 mumol of D-glucarate was quantitatively converted to 1 mumol each of D-glycerate and L lactate with concomitant utilization of 2 mumol of NADH. Using this method, D glucarate in serum was measured, along with quantitative recovery of authentic D glucarate from duplicate serum samples to which it had been added. Glucarate is a major serum organic acid, approximating blood pyruvate levels previously determined by others. PMID- 2187375 TI - Adaptation of fluorescence polarization immunoassay to the assay of macromolecules. AB - This paper describes an original methodology for determining macromolecular antigen levels by polarization of fluorescence. it involves the use of fluorescent derivatives of Fab fragments of a monoclonal antibody (Mr 50,000), whose fluorescence polarization rises significantly when it combines with a macromolecular antigen. An experimental system (Fab anti-aldosterone and aldosterone--bovine serum albumin (BSA)) is studied to test this methodology, which was then used to develop an immunoassay for human immunoglobulin M (IgM), using anti-mu chain Fabs. In the two assays, the binding stoichiometry of Fab/antigen was 10/1 and 8/1 for aldosterone--BSA and IgM, respectively. The lower limit of detection of the IgM assay was 0.8 microgram/ml and thus it was applicable to clinical detection of IgM concentrations. PMID- 2187376 TI - Noninvasive cardiac output: simultaneous comparison of two different methods with thermodilution. AB - The authors attempted to simultaneously measure cardiac output by thermodilution (COtd), thoracic bioimpedance (CObi), and suprasternal Doppler ultrasound (COdopp) in 68 patients. Subgroups separately compared included patients whose lungs were mechanically ventilated, patients undergoing cardiac surgery, aortic surgery, patients with dysrhythmias, and patients with sepsis. The authors also studied the value of the ventricular ejection time (VET) in evaluating the agreement of CObi and COdopp with COtd. Simultaneous CObi and COtd were available in a total of 56 patients (416 data sets) with an overall correlation coefficient r = 0.61, regression slope (m) of 0.52, intercept (y) of 2.46, and mean (CObi COtd) difference (bias) of -0.67 +/- 1.72 (SD) l/min. Simultaneous COdopp and COtd were available in 59 patients (446 data sets) with an overall r = 0.51, m of 0.53, y of 2.05, and bias of -0.79 +/- 1.95 l/min. CObi agreed most closely with COtd in patients whose lungs were mechanically ventilated, who had not undergone cardiac or aortic surgery, and with VET difference less than 40 ms (16 patients, 99 data sets; r = 0.74; m = 0.97; y = 0.15; bias = -0.02 +/- 1.53 l/min). COdopp agreed most closely with COtd in patients whose lungs were mechanically ventilated, who had not undergone cardiac or aortic surgery, and in sinus rhythm with VET difference less than 40 ms (10 patients, 45 data sets; r = 0.82; m = 0.98; y = -0.07; bias = -0.82 +/-1.03 l/min). VET by radial artery can help evaluate the reliability of CObi and COdopp. PMID- 2187378 TI - Effects of thiopental, pentobarbital, and ketamine on endothelin-induced constriction of porcine cerebral arteries. AB - Contractile mechanisms of endothelin, a newly isolated vasoactive substance from endothelium, were evaluated in anterior cerebral arteries (ACA). Furthermore, the effects of thiopental, pentobarbital, ketamine, and diltiazem on the endothelin induced cerebral vasoconstriction were also studied. Endothelin induced cerebral arterial contractions in concentrations above 3 X 10(-10) M. The median effective concentration (ED50: X10(-9) M) of endothelin was 2.1 +/- 0.7 (n = 6). Endothelin did not elicit contractions in preparations soaked in Ca2(+)-free solution, but addition of 2.5 mM Ca2+ to the baths induced marked contractions. Thiopental and pentobarbital attenuated endothelin-induced contractions at concentrations above 3 X 10(4) M, while ketamine was effective above 10(-3) M. In contrast, diltiazem decreased endothelin-induced vasoconstriction at 10(-6) M. The findings suggest that endothelin may cause contractions of porcine cerebral arteries by influx of Ca2+ through Ca2+ channels. The cerebral vasomotion induced by endothelin, however, does not seem to be influenced by clinical doses of barbiturates and ketamine. PMID- 2187377 TI - Postoperative apnea in former preterm infants: prospective comparison of spinal and general anesthesia. AB - Thirty-six former preterm infants undergoing inguinal hernia repair were studied. All were less than or equal to 51 weeks postconceptual age at the time of operation. Patients were randomly assigned to receive general or spinal anesthesia. Group 1 patients received general inhalational anesthesia with neuromuscular blockade. Group 2 patients received spinal anesthesia using 1% tetracaine 0.4-0.6 mg/kg in conjunction with an equal volume of 10% dextrose and 0.02 ml epinephrine 1:1000. In the first part of the study, infants randomized to receive spinal anesthesia also received sedation with im ketamine 1-2 mg/kg prior to placement of the spinal anesthetic (group 2 A). The remainder of group 2 patients did not receive sedation (group 2 B). Respiratory pattern and heart rate were monitored using an impedance pneumograph for at least 12 h postoperatively. Tracings were analyzed for evidence of apnea, periodic breathing and/or bradycardia by a pulmonologist unaware of the anesthetic technique utilized. None of the patients who received spinal anesthesia without ketamine sedation developed postoperative bradycardia, prolonged apnea, or periodic breathing. Eight of nine infants (89%) who received spinal anesthesia and adjunct intraoperative sedation with ketamine developed prolonged apnea with bradycardia. Two of the eight infants had no prior history of apnea. Five of the 16 patients (31%) who received general anesthesia developed prolonged apnea with bradycardia. Two of these five infants had no prior history of apnea. When infants with no prior history of apnea were analyzed separately, there was no statistically significant increased incidence of apnea in children receiving general versus spinal anesthesia with or without ketamine sedation. Because of the small numbers of patients studied, and the multiple factors that may influence the incidence of postoperative apnea (e.g., prior history of neonatal apnea), standard postoperative respiratory monitoring of these high-risk infants is still recommended following all anesthetic techniques. PMID- 2187379 TI - [An analog-digital system of external pressure for loco-regional treatment of deep venous thrombosis with fibrinolytics]. AB - A new method, by external pressure, analogic-digital system, is presented to be used in loco-regional treatment of "Deep Venous Thrombosis" with fibrinolytic agents; in order to allow a great concentration of drug and a better derivation of it toward the deep venous system. PMID- 2187380 TI - Differential effects of vasodilators on forearm and calf vessels. AB - Because the literature comparing the effects of vasodilators on forearm and calf vessels is very scarce, the authors compared different vasodilators used in cardiovascular medicine in a group of volunteers. The peripheral effects were measured in the sitting position by plethysmography at the calf and at the forearm. At the forearm, comparable dilator effects were seen in arteries and veins. At the calf there was a trend for arterial flow to decrease as venous capacitance increased. Vascular response seen in one limb was not representative of the whole circulation. The changes observed were dependent not only on the vascular area investigated but also on the dose used. PMID- 2187381 TI - Cardiac lymphoma associated with superior vena caval syndrome and cardiac tamponade: case history. AB - A sixty-three-year-old patient with malignant histiocytic lymphoma of the heart presented with both superior vena cava syndrome and cardiac tamponade. A two dimensional echocardiogram showed a large tumor mass in the right atrium and pericardial effusion with right ventricular compression. Superior and inferior vena cavagrams disclosed a lobulated tumor located in the right atrium that extended into and obstructed the superior vena cava. After the pericardial effusion was drained and the diagnosis was established, the patient was irradiated and given chemotherapy with resolution of the tamponade and superior vena cava obstruction. PMID- 2187382 TI - Hyperdynamic sepsis modifies a PEEP-mediated redistribution in organ blood flows. AB - Changes in organ blood flow (Q) produced by 20 cm H2O positive end-expiratory pressure (PEEP) were measured before and after the induction of hyperdynamic sepsis in nine unanesthetized sheep. During the baseline nonseptic study, PEEP was associated with a 9% fall in thermodilution-measured systemic Q, although arterial perfusing pressures were unaffected. Concurrently, microsphere-derived Q was maintained to the brain and heart, but fell to liver, spleen, pancreas, kidney, large intestine, and gastrocnemius. Twenty-four to 36 h after cecal ligation and perforation, a pre-PEEP septic study demonstrated an increase in all of the cardiac index (CI) (+43%) and systemic O2 delivery (+54%) when compared with the nonseptic study, whereas whole-body O2 extraction (-30%) was depressed. Although PEEP depressed systemic Q (-17%) during the septic study to a greater extent than during the nonseptic study (p less than 0.02), absolute organ Q fell only to pancreas, liver, and spleen. Relative to the simultaneous fall in the CI, Q to some splanchnic organs was not depressed by PEEP to the same magnitude in the septic as in the nonseptic study. When an infusion of Ringer's lactate (993 +/- 295 ml) subsequently restored systemic Q to pre-PEEP septic levels, individual flows that had been depressed by PEEP were not restored. Furthermore, Q-kidney continued to fall, such that the postfluid Q-kidney (-19%) was significantly less than was demonstrated in the pre-PEEP septic study. We postulate that differences noted in the distribution of organ Q between the nonseptic and hyperdynamic septic studies after the application of PEEP were secondary to the vasculopathy of sepsis and/or an alteration in the function of specific organ microcirculations. However, these data do not address whether the changes in organ Q distribution after a PEEP-mediated depression in systemic Q during sepsis significantly restricted tissue DO2. The inability to acutely reverse the PEEP-mediated changes in organ Q after restoring systemic Q by a fluid infusion also suggests the need to evaluate alternative methods of support to organ Q in acute respiratory failure secondary to sepsis when the addition of PEEP acutely depresses systemic DO2. PMID- 2187383 TI - Regional pulmonary blood flow in piglets during group B streptococcal bacteremia. AB - Shunt fraction (QS/QT) and perfusion to hypoxic lung regions increase when pulmonary vascular driving pressure (PVDP) is raised by increasing pulmonary blood flow or enlarging the size of the hypoxic region. We hypothesized that perfusion to collapsed areas would similarly increase when PVDP was increased by a circulating pulmonary vasoconstrictor. Group B streptococci (GBS) were infused into 10 young piglets with left lung atelectasis to produce pulmonary vasoconstriction and determine if perfusion to collapsed regions (QL/QT) and intrapulmonary QS/QT increased as pulmonary vascular resistance (PVR) increased. Left lung collapse alone increased PVR from 11 +/- 3 to 18 +/- 10 mm Hg/L/min and QS/QT from 1.9 +/- 1.4% to 8.3 +/- 6.4%; QL/QT decreased from 44 +/- 1% to 10 +/- 7% of total pulmonary blood flow (p less than 0.02). Intravenous GBS increased PVDP from 11 +/- 3 to 27 +/- 4 mm Hg and further increased PVR from 18 +/- 10 to 33 +/- 12 mm Hg/L/min (p less than 0.02) but did not change cardiac output, QS/QT, or QL/QT. Changes in QL/QT and QS/QT are not predicted by changes in PVDP alone but also depend upon the site and nature of pulmonary vasoconstriction in infants with regional lung disease. PMID- 2187384 TI - The reduction of weaning time from mechanical ventilation using tidal volume and relaxation biofeedback. AB - We sought to determine if biofeedback could reduce weaning time for the hard-to wean patient by improving important weaning factors that are not effectively dealt with by present weaning methods. These include respiratory muscle electromyograph (EMG) efficiency, respiratory drive, and the anxiety of the ventilator-dependent patient. After the patient had received mechanical ventilation for 7 days and the day weaning began (start), the patient was randomly assigned to biofeedback or to the control group. There were 20 patients assigned to each group, with mean ages of 60.2 (biofeedback) and 59.3 (control) yr. The patients assigned to the biofeedback group received daily, until extubation or being placed on no resuscitation status (termination), frontalis electromyographic (EMG) relaxation feedback for anxiety reduction and improved respiratory muscle EMG efficiency, tidal volume/diaphragm EMG (VT/DAP), and VT feedback for increasing VT and respiratory drive defined as tidal volume/inspiratory time (VT/TI). The control group was visited daily to control for attention and reassurance. The results showed a significant (p less than 0.01) reduction in mean ventilator days for the biofeedback group of 20.6 +/- 8.9 SD compared with 32.6 +/- 17.6 SD mean days for the control group. From start to termination, there was a significant (p less than 0.01) increase in baseline VT, from 295 +/- 41 to 415 +/- 45 ml, and a significant (p less than 0.02) increase in VT/DAP, from 0.33 +/- 0.09 to 0.94 +/- 0.22 L/mV for the biofeedback group but no significant change in these parameters for the control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2187385 TI - Effects of D-galactosamine-induced acute liver injury on mortality and pulmonary responses to Escherichia coli lipopolysaccharide. Modulation by arachidonic acid metabolites. AB - Multiple extrapulmonary organ system failures increase mortality, permeability edema, and alveolar inflammation during gram-negative sepsis because of abnormal regulation of host inflammatory responses. We tested the hypothesis that acute hepatocytic injury induced by the selective hepatotoxin, D-galactosamine (GalN), augments mortality and amplifies pulmonary microvascular permeability to albumin and neutrophilic influx after administering Escherichia coli lipopolysaccharide (LPS) 24 h later by impairing the metabolism of endogenously synthesized products of arachidonic acid. We determined the lung extravascular leak of 125I-human serum albumin measured at multiple time points after LPS and enumerated polymorphonuclear leukocytes (PMNs) in bronchoalveolar lavage fluid (BALF). Because the liver is important in prostaglandin (PG) and leukotriene (LT) metabolism, we measured plasma concentrations of 6-keto-PGF1 alpha and thromboxane B2 (TxB2) in addition to paired plasma BALF concentrations of LTB4 and BALF LTC4 60 min and 24 h after LPS. We further assessed the protective effects of a single 20-mg/kg injection given intraperitoneally (i.p.) of the LTA4 synthetase inhibitor, diethylcarbamazine (DEC). After 400 mg/kg GalN, LPS at 2.5 or 1.25 mg/kg i.p. increased mortality (p less than 0.001), albumin leak 60 and 90 min after LPS (p less than 0.05), plasma 6-keto-PGF1 alpha, TxB2, and LTB4 levels and BALF LTC4 within 60 min (p less than 0.05). LTB4 and LTC4 levels in BALF 24 h later were similarly increased (p less than 0.05) as were bronchoalveolar PMNs (p less than 0.001). DEC improved mortality and albumin leak (p less than 0.001), reduced lung influx of PMNs and peripheral leukocytosis (p less than 0.05), attenuated plasma LTB4 and BALF LTC4 levels 60 min after LPS (p less than 0.05), and decreased BALF LTB4 and LTC4 at 24 h (p less than 0.05), but was associated with higher plasma 6-keto-PGF1 alpha and TxB2 values at 60 min. Changes in eicosanoid levels and modulation of responses by DEC in this model suggest that impaired metabolism of endogenously synthesized leukotriences by the damaged liver underlies these phenomena. We conclude that this mechanism may enhance septic lung injury during acute liver dysfunction. PMID- 2187386 TI - Distribution of smooth muscles along the bronchial tree. A morphometric study of ordinary autopsy lungs. AB - A morphometric pilot study was performed on airway smooth muscle in 20 autopsy lungs with no history of chronic obstructive pulmonary disease (COPD) to establish a basis for the systematic analysis of the behavior of airway muscles in bronchial asthma or COPD. A total of 514 samples of cross-sectioned airways were taken from these lungs, covering as uniformly as possible the whole range from segmental bronchi to terminal bronchioles. In each airway, the perimeter length L of the epithelial basement membrane and the area S of mural smooth muscles were measured using a digital image analyzer, and the thickness D of smooth muscles and the radius R were determined in a standardized state in which the airway was stretched into a circle without changing L or S. On bilogarithmic coordinates, D was found to correlate significantly with R not only in individual cases but also in the total pooled data. D/R, the relative thickness of muscles, increased toward the periphery of the airways. In a theoretical application of Laplace's law to the physical conditions dominating the airway wall, this tendency in D/R suggests that the activity of airflow regulation is highest in terminal airways. PMID- 2187387 TI - Hyperreactive site in the airway tree of asthmatic patients revealed by thickening of bronchial muscles. A morphometric study. AB - Under the assumption that the more hyperreactive the bronchial muscles are, the greater their work hypertrophy, we analyzed the distribution of hypertrophic smooth muscles along airways to see where in the bronchial tree asthmatic constrictions mainly occur. Autopsy lungs from 16 patients with bronchial asthma, 13 with other COPDs, and 20 controls were submitted to morphometry of the bronchial muscles. In microscopic slides, cross sections of airways were taken from the segmental bronchi to the terminal bronchioles. The perimeter length L of the basement membrane and the area S of muscles were measured, and the anatomic radius R and the muscular thickness D were calculated in a standardized circular state, in which the basement membrane was stretched into a circle without changing L or S. On bilogarithmic coordinates of D and R on which data from the asthmatics were pooled, it was shown that hypertrophy of muscles was the most pronounced in larger bronchi where constriction was most likely to occur. Closer analysis of patients, however, revealed that besides this typical pattern, which we designated Type I asthma, there was a group of patients (Type II) in whom hypertrophy involved the entire range of airways, including the bronchioles, suggesting that the site of asthmatic response varies among patients. In nonasthmatic patients with COPD, only mild hypertrophy of muscles was found in the large airways, despite the presence of obstructive lesions mainly in the small airways. PMID- 2187389 TI - Large-volume paracentesis in treatment of ascites. PMID- 2187388 TI - Pulmonary infectious complications of human immunodeficiency virus infection. Part I. PMID- 2187390 TI - A tribute to Edward Huth, Editor. PMID- 2187391 TI - Glycemic control and neuropsychologic function during hypoglycemia in patients with insulin-dependent diabetes mellitus. AB - STUDY OBJECTIVE: To evaluate counterregulatory hormone secretion and neuropsychologic function during hypoglycemia in two groups of patients with insulin-dependent diabetes mellitus: those with good and those with poor glycemic control. DESIGN: Cross-sectional physiologic and neuropsychologic evaluation. SETTING: Clinical research unit of a referral-based diabetes clinic. PATIENTS: Eight patients with well controlled diabetes (glycosylated hemoglobin [HgbA1], 8.0% +/- 0.2%), nine patients with poorly controlled diabetes (HgbA1, 11.8% +/- 0.4%), and ten healthy persons. INTERVENTIONS: The insulin clamp technique was used to produce a stepwise decline in plasma glucose from 5.0 to 2.2 mmol/L over 3 hours. Tests of attention, memory, visual-spatial skills, visual-motor skills, and global cognition; a symptom survey; and counterregulatory hormone measurements were done at glucose decrements of 0.6 mmol/L. MEASUREMENTS AND MAIN RESULTS: Patients with well controlled diabetes did not differ statistically from those with poorly controlled diabetes regarding the median glucose threshold for dysfunction in visual-spatial skills, visual-motor skills, or global cognition. In contrast, glycemic thresholds for an increase in adrenergic symptoms and release of epinephrine, norepinephrine, cortisol, and growth hormone were lower in patients with well controlled diabetes than in those with poorly controlled diabetes (P less than 0.05 to 0.005). CONCLUSIONS: Despite alterations in the glucose levels at which adrenergic symptoms of hypoglycemia occur and counterregulation begins, there is no statistically detectable change in the glucose threshold at which cognitive deterioration occurs in diabetic persons with strict glycemic control. This dissociation of neuropsychologic function and counterregulatory hormone secretion suggests that diabetic patients with good glycemic control are at increased risk for developing cognitive impairment before the onset of adrenergic symptoms during hypoglycemia. PMID- 2187392 TI - The pituitary "incidentaloma". AB - PURPOSE: To review evidence related to sellar masses that might be found incidentally on various radiologic procedures, including their differential diagnosis and recommendations for their evaluation and treatment. DATA IDENTIFICATION: An English-language literature search using bibliographic reviews of textbooks and review articles. STUDY SELECTION: Articles were selected on the basis of providing data on the autopsy prevalence of sellar masses, the radiologic and endocrinologic evaluation of such masses, and the prognostic aspects of pituitary adenomas. DATA EXTRACTION: Twelve studies relating autopsy findings, 6 studies describing radiologic characteristics, and 26 articles reviewing various endocrine aspects of pituitary adenomas were evaluated. RESULTS OF DATA SYNTHESIS: Pituitary adenoma is the most common incidental sellar mass. Scanning techniques are of great importance in differentiating the pituitary adenoma from other mass lesions. Autopsy and radiologic studies suggest that microadenomas (less than 10 mm in diameter) may be present in 10% to 20% of the population but that macroadenomas (greater than 10 mm in diameter) are quite rare. Hormone oversecretion by an adenoma may be asymptomatic but, when present, is very helpful in the differential diagnosis. CONCLUSIONS: For adenomas found to be hypersecreting, therapy is as indicated for that specific tumor type. If there is no evidence of hormone oversecretion from microadenomas, we suggest a conservative approach with repeat scanning done at yearly intervals, initially, and subsequently less frequently. Macroadenomas, because they have already indicated some propensity for growth, should either be surgically removed or, if completely asymptomatic, followed closely with repeat scans at 6- to 12-month intervals. PMID- 2187393 TI - The myelodysplastic syndromes: current approaches to therapy. AB - PURPOSE: To review the current therapeutic options for patients with the myelodysplastic syndromes. DATA IDENTIFICATION: Studies reported between 1968 and September 1989 were identified through computer searches using MEDLINE and through extensive searching of bibliographies of identified articles. STUDY SELECTION: All articles, abstracts, and reviews were evaluated, and those that contained therapeutic data were analyzed for response rates, survival, and toxicity. RESULTS OF DATA SYNTHESIS: Therapies for the myelodysplastic syndromes have included hormones, chemotherapy, bone marrow transplantation, and differentiating agents, including hematopoietic growth factors. With the exception of bone marrow transplantation, none is curative or increases survival. Hematopoietic growth factors are of interest for clinical trials, because they increase the number of neutrophils and, occasionally, the number of platelets in patients with the myelodysplastic syndromes. Nonetheless, hematopoietic growth factors are not without toxicity; most notably, they are associated with a risk for acceleration to acute myeloid leukemia, and their effect on survival remains unknown. CONCLUSIONS: Standard therapy for the myelodysplastic syndromes is supportive care. When the disease progresses, patients with aggressive histologic or other poor-risk features should be considered for aggressive chemotherapy, with or without growth factors, or bone marrow transplantation. Patients with good prognostic features are candidates for therapy with growth factors or other potential differentiating agents. Carefully designed and conducted clinical trials that incorporate correlative laboratory science are essential to developing a more rational approach to therapy. PMID- 2187394 TI - Medical futility: its meaning and ethical implications. AB - The notion of medical futility has quantitative and qualitative roots that offer a practical approach to its definition and application. Applying these traditions to contemporary medical practice, we propose that when physicians conclude (either through personal experience, experiences shared with colleagues, or consideration of published empiric data) that in the last 100 cases a medical treatment has been useless, they should regard that treatment as futile. If a treatment merely preserves permanent unconsciousness or cannot end dependence on intensive medical care, the treatment should be considered futile. Unlike decision analysis, which defines the expected gain from a treatment by the joint product of probability of success and utility of outcome, our definition of futility treats probability and utility as independent thresholds. Futility should be distinguished from such concepts as theoretical impossibility, such expressions as "uncommon" or "rare," and emotional terms like "hopelessness." In judging futility, physicians must distinguish between an effect, which is limited to some part of the patient's body, and a benefit, which appreciably improves the person as a whole. Treatment that fails to provide the latter, whether or not it achieves the former, is "futile". Although exceptions and cautions should be borne in mind, we submit that physicians can judge a treatment to be futile and are entitled to withhold a procedure on this basis. In these cases, physicians should act in concert with other health care professionals, but need not obtain consent from patients or family members. PMID- 2187395 TI - A residency-based information system. AB - The medical literature has grown to an unmanageable size, and we need to develop information systems that provide better accessibility. An internal medicine residency program is an ideal setting for developing a system in which articles are screened for usefulness in clinical decision making and organized to be rapidly accessible and relatively inexpensive to use. In our residency training program, we use clinical problem-solving, journal club article review, and teaching conference preparation to generate appropriate articles from PAPERCHASE (MEDLINE) database searches. With the chief resident supervising the process, articles are then selected and organized in a computerized article file. The software program, Reference Manager (Research Information Systems, Inc., Encinitas, California), stores article citations and supports searches using standard, medical subject heading vocabulary key words. In an 18-month period, residents have collected more than 1800 references appropriate to clinical decision making and have established an article file that is now used daily as a medical information source. PMID- 2187396 TI - Candidal endocarditis and treatment with fluconazole and granulocyte-macrophage colony-stimulating factor. PMID- 2187397 TI - [Conservative transmandibular lateral pharyngectomy in cancer of the lateral oropharyngeal wall]. AB - The authors present conservative transmandibular lateral pharyngectomy (CTLP) as a substitute for BPTM operations in cancers of the tonsillar region. The mandible is sectioned along the symphyses and the oropharynx is widely exposed through an incision of the pelvilingual sulcus. The authors propose a primary operability criterion that allows to salvage the mandibular angle, which is usually sacrificed. This can be assessed peroperatively by testing the possibility to cleave and spread inwardly the pharyngomandibular region following detachment of the pterygoid muscles. The functional and cosmetic benefits of this method are obvious and should commend its more frequent utilization. PMID- 2187398 TI - [The scapular osteocutaneous flap. Technic, indications in cervicofacial surgery]. AB - The authors describe 10 cases of mandibular reconstruction following transmandibular buccopharyngectomy, using scapular osteocutaneous flaps. Repair of mandibular substance loss due to neoplastic surgery becomes a problem. Composite bone resections are associated with mucous and muscular defect formation. There is dual advantage in using this type of flap: on the one hand, reliability is great, independently of the case (revisions or other types of surgery) because of the presence of constant elements in the vascular pedicle; on the other hand, the cutaneous flap and the bone transplant are independent from each other, such plasticity affording equally successful symphyseal and lateral repair. PMID- 2187399 TI - [Results of surgery of acoustic neuroma via translabyrinth and suprapetrous approaches. Development of a classification by House and Brackmann based on facial function]. AB - Two studies were conducted consecutively on two series of post-operative acoustic neurinoma patients. The first one included 104 patients over a period spanning from January 1982 through April 1986; the second one bore on 75 cases enrolled between October 1985 and April 1988. Post-operative complications, sequelae, and findings were analyzed. As far as facial function was concerned, this was assessed on the basis of a classification worked out by J.W. House and D.E. Brackmann. For the first series (93 patients tested, 86 followed up and 7 who completed and returned a form arranged from Brackmann's questionnaire), the following results were obtained: 94% with anatomically intact nerves, including 50.0% grade I; 8.6% grade II; 10.7% grade III; 12.8% grade IV; 4.3% grade V, and 2.2% grade VI cases. 10 nerve sections pertaining to grade III and grade IV surgical repair cases including 10 hypoglossofacial anatomoses were reported. In the second series, 75 patients were followed up for at least 2 years. The facial nerve condition was recorded at the end of the operation, corresponding to the beginning of the nerve recuperation period. A very tight relationship was noted between the nerve condition and the end result as reflected by facial function; such correlation was also found to exist between facial function and tumor size. Likewise, end-point facial function was strictly dependent upon the incipient recuperation phase, whenever palsy had been complete or partial post-operatively. That is to say, if recovery started out after the third month following surgery, the affected hemiface would never retrieve its normal or subnormal function (grade I and II as per J.W. House and D.E. Brackmann). In this series, facial function was restored in 45%, 15%, 21%, 11%, 1%, and 0 cases corresponding to grade I, II, III, IV, V and VI, respectively. Five grade III and IV nerve sections were repaired via five hypoglossofacial anastomosis operations. We propose a slight modification be brought to the House-Brackmann classification. The aim of this study was to accurately assess the complications and sequelae secondary to surgical ablation of unilateral acoustic neurinoma by an otoneurosurgical team utilizing almost exclusively the broadened translabyrinthic (B.TL) and medial cerebral fossa or supra-petrous (SP) approaches Despite achievements realized since W.F. House [23] described those, the main problem encountered has been-excluding major complications which are fortunately rare, remains the preservation of normal or subnormal facial function. PMID- 2187401 TI - Low-pH-induced effects on patterns of protein synthesis and on internal pH in Escherichia coli and Salmonella typhimurium. AB - Escherichia coli and Salmonella typhimurium were grown in a supplemented minimal medium (SMM) at a pH of 7.0 or 5.0 or were shifted from pH 7.0 to 5.0. Two dimensional gel electrophoretic analysis of proteins labeled with H2(35)SO4 for 20 min during the shift showed that in E. coli, 13 polypeptides were elevated 1.5 to 4-fold, whereas in S. typhimurium, 19 polypeptides were increased 2- to 14 fold over the pH 7.0 control. Upon long-term growth at pH 5.0, almost double the number of polypeptides were elevated twofold or more in S. typhimurium compared with E. coli. In E. coli, there was no apparent induction of heat shock proteins upon growth at pH 5.0 in SMM. However, growth of E. coli in a complex broth to pH 5.0, or subsequent growth of fresh E. coli cells in the filtrate from this culture, showed that a subset of five polypeptides is uniquely induced by low pH. Two of these polypeptides, D60.5, the inducible lysyl-tRNA synthetase, and C62.5, are known heat shock proteins. Measurements of the internal pH (pHi) and growth rates of both organisms were made during growth in SMM at pH 7.0, pH 5.0, and upon the pH shift. The data show that the pHi of E. coli decreases more severely than that of S. typhimurium at an external pH of 5.0; the growth rate of E. coli is about one-half that of S. typhimurium at this pH, whereas the two organisms have the same growth rate at pH 7.0. The two-dimensional gel, growth, and pHi experiments collectively suggest that, at least in SMM, S. typhimurium is more adaptive to low-pH stress than is E. coli. PMID- 2187400 TI - Comparison of growth, acetate production, and acetate inhibition of Escherichia coli strains in batch and fed-batch fermentations. AB - The growth characteristics and acetate production of several Escherichia coli strains were compared by using shake flasks, batch fermentations, and glucose feedback-controlled fed-batch fermentations to assess the potential of each strain to grow at high cell densities. Of the E. coli strains tested, including JM105, B, W3110, W3100, HB101, DH1, CSH50, MC1060, JRG1046, and JRG1061, strains JM105 and B were found to have the greatest relative biomass accumulation, strain MC1060 accumulated the highest concentrations of acetic acid, and strain B had the highest growth rates under the conditions tested. In glucose-feedback controlled fed-batch fermentations, strains B and JM105 produced only 2 g of acetate.liter-1 while accumulating up to 30 g of biomass.liter-1. Under identical conditions, strains HB101 and MC1060 accumulated less than 10 g of biomass.liter 1 and strain MC1060 produced 8 g of acetate.liter-1. The addition of various concentrations of sodium acetate to the growth medium resulted in a logarithmic decrease, with respect to acetate concentration, in the growth rates of E. coli JM105, JM105(pOS4201), and JRG1061. These data indicated that the growth of the E. coli strains was likely to be inhibited by the acetate they produced when grown on media containing glucose. A model for the inhibition of growth of E. coli by acetate was derived from these experiments to explain the inhibition of acetate on E. coli strains at neutral pH. PMID- 2187402 TI - Shiga-like-toxin-producing Escherichia coli in retail meats and cattle in Thailand. AB - Specific DNA probes were used to identify Shiga-like toxin I (SLT I)- and SLT II producing Escherichia coli in vegetables, meats, cattle, and farm animals in Thailand. SLT-producing E. coli was isolated from 9% of market beef specimens, from 8 to 28% of fresh beef specimens at slaughterhouses, and from 11 to 84% of fecal specimens from cattle. Animals were frequently infected with several different SLT-producing E. coli types that hybridized with either the SLT I, SLT II, or both SLT probes. Of 119 SLT-producing E. coli isolates, 24% hybridized with the SLT I probe, 31% hybridized with the SLT II probe, and 44% hybridized with both SLT probes. The enterohemorrhagic E. coli plasmid probe hybridized with 64% (68 of 106) of SLT-producing E. coli isolates from food and cattle and with 8% (17 of 201) of E. coli isolates from pigs. No SLT-producing E. coli was detected in pigs. Seventy-six percent (26 of 34) of E. coli isolates that hybridized with the SLT II probe were cytotoxic to Vero but not to HeLa cells, suggesting that they produced the variant of SLT II. The high prevalence of SLT producing E. coli in beef-producing animals suggests that exposure to animals and eating beef may pose a health risk for acquiring enterohemorrhagic E. coli infections in Thailand. PMID- 2187403 TI - Simplified Henry technique for initial recognition of Listeria colonies. AB - The Henry oblique transmitted-light viewing technique was modified to provide a more precise, convenient, and familiar manner with which to read (score) and recognize colonies of listeriae by their distinct bluish cast. The simplified technique involved illuminating each colony directly with a high-intensity lamp while viewing it with a hand lens at a precise angle in place of a scanning light microscope. PMID- 2187404 TI - Purification and properties of an endo-1,4-beta-glucanase translated from a Clostridium josui gene in Escherichia coli. AB - An endoglucanase encoded by a gene of Clostridium josui was expressed in Escherichia coli and purified. The homogeneous enzyme, with a molecular weight of 39,000, revealed maximum endoglucanase activity at pH 7.2 to 7.5 and a temperature of 65 to 70 degrees C. The enzyme was stable at a temperature lower than 45 degrees C (the growth temperature of the bacterium) in the range of pH 4.5 to 9.0. The amino acid sequence of the enzyme at the N terminus was Val-Glu Glu-Asp-Ser-Ser-His-Leu-Ile-Thr-Asn-Gln-Ala-Lys-Lys----. The enzyme hydrolyzed cellotetraose to cellobiose and then transferred cellobiose to the residual cellotetraose. The resulting cellohexaose was cleaved to cellotriose. PMID- 2187405 TI - Efficient DNA transformation of Bradyrhizobium japonicum by electroporation. AB - Intact cells of Bradyrhizobium japonicum USDA 110 were transformed with a 30 kilobase plasmid to efficiencies of 10(6) to 10(7) transformants per microgram by high-voltage electroporation. The technique was reliable and simple, with single colonies arising from transformed cells within 5 days of antibiotic selection. Plasmid DNA from B. japonicum transformed the Bradyrhizobium (Arachis) sp. with high efficiency, while the same plasmid extracted from Escherichia coli transformed B. japonicum at very low efficiency. The electrical conditions that resulted in the highest efficiencies were high voltage (10.5 to 12.5 kV/cm) and short pulse length (6 to 7 ms). A linear increase in the number of transformants was observed as DNA concentration was increased over 4 orders of magnitude; saturation appeared to begin between 120 ng/ml and 1.2 micrograms/ml. This novel method of transformation should enhance B. japonicum genetic research by providing a valuable alternative to conjugal mating, which is currently the only efficient, widely used means of introducing DNA into this organism. PMID- 2187406 TI - Salmonella-TEK, a rapid screening method for Salmonella species in food. AB - A micro-enzyme-linked immunosorbent assay (micro-ELISA) using the Salmonella-TEK screen kit was tested for the detection of Salmonella spp. in pure cultures as well as in 30 artificially contaminated food samples and in 45 naturally contaminated food samples. Different raw, fleshy foods and processed foods were used as test products. The artificially contaminated minced meat samples were preenriched in buffered peptone water, and after incubation, different selective enrichment broths were tested. The micro-ELISA optical density values after enrichment and isolation of the different broths were very analogous. The quickest method to detect Salmonella spp. in different foods is to enrich them with Salmosyst broth, which reduces the total analysis time to 31 h. The Salmonella-TEK kit for Salmonella spp. provides a promising test for the detection of Salmonella antigens in food even when they are present at a low concentration (1 to 5 CFU/25 g). The cross-reaction of the anti-Salmonella antibodies, especially to other gram-negative bacteria, is nil. PMID- 2187407 TI - Microcosm for assessing survival of genetically engineered microorganisms in aquatic environments. AB - Laboratory-contained microcosms are important for studying the fate and survival of genetically engineered microorganisms. In this study, we describe a simple aquatic microcosm that utilizes survival chambers in a flowthrough or static renewal system. The model was used to study the survival of genetically engineered and wild-type strains of Escherichia coli and Pseudomonas putida in the lake water environment. Temperature-dependent studies indicated that the genetically engineered microorganisms survived better or at least as well as their wild-type counterparts at 15, 25, and 30 degrees C. The genetic determinants of the genetically engineered microorganisms also remained fairly stable within the host cell under the tested conditions. In the presence of organisms indigenous to lake water, E. coli was eliminated after 20 days, whereas P. putida showed an initial decline but was able to stabilize its population after 5 days. A herbicide, Hydrothol-191, caused a significant decline in numbers of P. putida, but no significant difference was observed between the genetically engineered microorganisms and the wild-type strain. The microcosm described is simple, can be easily adapted to study a variety of environmental variables, and has the advantage that the organisms tested are constantly exposed to test waters that are continuously renewed. PMID- 2187408 TI - Application of a ribosomal DNA integration vector in the construction of a brewer's yeast having alpha-acetolactate decarboxylase activity. AB - An integration plasmid, pIARL28, containing the ribosomal DNA gene as a homologous recombination sequence was constructed for introduction of the alpha acetolactate decarboxylase gene into brewer's yeast. The transformation efficiency of pIARL28 was 20- to 50-fold higher than those of the other YIp vectors, as yeast cells had approximately 140 copies of the ribosomal DNA gene. All transformants showed very high alpha-acetolactate decarboxylase activity due to the multiple integrated copies of the plasmid. The transformants were grown in nonselective conditions, and segregants which had maintained the alpha acetolactate decarboxylase expression cassette but no other vector sequences were isolated. Southern analysis showed that these marker-excised segregants contained more than 20 copies of the alpha-acetolactate decarboxylase gene and were stably maintained under nonselective conditions. Fermentation tests confirmed that the diacetyl concentration was considerably reduced in wort fermented by these marker excised segregants. The degree of reduction was related to the copy number of the alpha-acetolactate decarboxylase gene. PMID- 2187409 TI - Efficacy of beta-glucuronidase assay for identification of Escherichia coli by the defined-substrate technology. AB - In 1976, Kilian and Bulow described the association of beta-glucuronidase with the genus Escherichia (97% positive) and suggested that a beta-glucuronidase assay would be a useful identification test. Since that report, papers about the sensitivity and specificity of this enzyme for the identification of Escherichia coli from clinical sources, food, seawater, potable-water supplies, and various environmental sources have appeared. A study was undertaken to determine the efficacy and specificity of the defined-substrate technology beta-glucuronidase (Colilert) assay for the identification of this species from fecal samples. A total of 460 human, 105 cow, and 55 horse E. coli isolates were tested. Results showed 95.5% beta-glucuronidase-positive isolates in 24 h and 99.5% positive after 28 h of incubation. Only one E. coli isolate was negative. There were no significant differences in the percentage of beta-glucuronidase-positive isolates among the human or animal isolates. There were no non-E. coli isolates that were positive. All subjects carried beta-glucuronidase-positive E. coli. PMID- 2187410 TI - Evaluation of DNA probes for detection of Shiga-like-toxin-producing Escherichia coli in food and calf fecal samples. AB - The use of DNA probes for Shiga-like toxin I (SLT-I) and SLT-II for detection of SLT-producing Escherichia coli (SLTEC) in foods and calf fecal samples was evaluated. Enrichment cultures were prepared from food or fecal samples. Colonies formed by plating of enrichment cultures were probed for SLTEC by colony hybridization. Alternatively, enrichment cultures were analyzed for SLTEC presence by dot blot. The lowest detected concentration of SLTEC in sample homogenates inoculated with E. coli O157:H7 corresponded to 1.3 CFU/g of sample. Of the 44 food samples and 28 fecal samples from dairy calves tested by the colony hybridization method, 4 food samples, including ground beef, raw goat milk, blueberries, and surimi-based delicatessen salad, and 9 calf fecal samples were positive with the SLT probes. The dot blot technique yielded results within 48 h and can be used as a fast and sensitive method of detection for SLTEC in foods and calf fecal samples. The colony hybridization technique took 3 to 4 days but permits recovery of the positive colonies when desired. PMID- 2187411 TI - Comparison of the limulus amebocyte lysate test and gas chromatography-mass spectrometry for measuring lipopolysaccharides (endotoxins) in airborne dust from poultry-processing industries. AB - The lipopolysaccharide (endotoxin) content in airborne dust samples from three different poultry slaughterhouses was determined with both the chromogenic Limulus amebocyte lysate assay and gas chromatography-mass spectrometry analysis of lipopolysaccharide-derived 3-hydroxy fatty acids. Gram-negative cell walls were also measured by using two-dimensional gas chromatography/electron-capture analysis of diaminopimelic acid originating from the peptidoglycan. The correlation between the results of the Limulus assay and those of gas chromatography-mass spectrometry for determination of the lipopolysaccharide content in the dust samples was poor, whereas a good correlation was obtained between lipopolysaccharide and diaminopimelic acid concentrations with the gas chromatographic methods. The results suggest that it is predominantly cell-wall dissociated lipopolysaccharides that are measured with the Limulus assay, whereas the gas chromatographic methods allow determination of total concentrations of lipopolysaccharide, including Limulus-inactive lipopolysaccharide, gram-negative cells, and cellular debris. PMID- 2187412 TI - Improved expression of human interleukin-2 in high-cell-density fermentor cultures of Escherichia coli K-12 by a phosphotransacetylase mutant. AB - A fluoroacetate-resistant mutant of Escherichia coli K-12 (MM-294) accumulated less acetate in the medium during growth to high cell density in fermentor cultures and was shown to be defective in its phosphotransacetylase activity. The mutant had an improved ability to continue growing during induction of interleukin-2 (IL-2) synthesis, and in fermentor cultures it gave a higher level of specific IL-2 accumulation than its parent during expression under control of the temperature-sensitive pL promoter. In flask cultures at lower cell density, the mutant again produced less acetate than the parent, although both showed a much lower level of acetate accumulation than that seen in fermentors at high cell density. Both showed a higher specific expression level of IL-2 in flask cultures, and there was a greater difference between the mutant and its parent in the final extent of specific IL-2 accumulation in fermentor cultures compared with flask cultures. Thus, the concentration of acetate in the medium, which was much higher in fermentor cultures (greater than or equal to 300 mM after 5 h of induction) than in flask cultures (less than or equal to mM) of the parent organism, was a significant factor in limiting expression of the heterologous protein product, IL-2. The acetate kinase-phosphotransacetylase pathway was therefore a major source of acetate formation in these cultures. Blocking this pathway improved accumulation of IL-2 and did not slow growth. PMID- 2187413 TI - Production of Escherichia coli-specific hybridomas by using gnotobiotic mice. AB - Monoclonal antibodies provide a rapid and specific means of direct detection of microorganisms in water and food samples. However, monoclonal antibodies specific for some bacteria are difficult to obtain; a good example of such a bacterium is Escherichia coli. Gnotobiotic BALB/c mice immunized with whole-cell preparations of heat-treated strains of E. coli and subjected to high-frequency antigen injection showed a significant increase in the number of specific hybridomas produced. Fusions obtained by using regular BALB/c mice immunized by using standard immunization protocols produced nonspecific hybridomas. Twenty-one stable hybridomas that did not cross-react with Klebsiella pneumoniae ATCC 13883 or Citrobacter freundii 1604770 were obtained from gnotobiotic mice. The bacterial strains were selected for the specificity tests because of their high cross-reactivity, which has been detected in previous fusion experiments. The method of immunization described here offers the potential of improving the production of highly specific hybridomas for bacteria which have been difficult to obtain. PMID- 2187414 TI - Fluorescent-antibody method useful for detecting viable but nonculturable Salmonella spp. in chlorinated wastewater. AB - An indirect fluorescent-antibody (IFA) technique, which employed adsorbed Behring polyvalent I O antiserum, was used to detect Salmonella spp. in environmental water systems. The IFA method used in this study detected 95% of Salmonella serotypes encountered in human infections in France, with a sensitivity threshold of 7.5 x 10(3) bacteria per ml of wastewater. Specificity was assessed by testing IFA against Salmonella-free seawater and a variety of bacteria other than Salmonella spp. When used to examine raw and chlorinated wastewater over a 2 month period, the IFA method was successful in detecting Salmonella spp. in all 12 of the samples examined, with total numbers determined to be 4.5 x 10(5) to 3.3 x 10(7) salmonellae per 100 ml. In comparison, for the same samples, enumeration by culture, using the most-probable-number technique, was effective in detecting Salmonella spp. in only four of eight raw-water samples and one of four chlorinated water samples tested. Three samples were further tested by using the direct viable count procedure combined with IFA and results showed that 5 to 31.5% of the Salmonella spp. enumerated by this method in chlorinated water were substrate responsive. PMID- 2187415 TI - Cytokines and eicosanoids in rheumatic diseases. PMID- 2187416 TI - Pigmented villonodular synovitis. PMID- 2187417 TI - A review on the occasion of the retirement of Professor Philip Wood. PMID- 2187418 TI - Acquired chondronecrosis. AB - Zonal necrosis of chondrocytes is a characteristic feature of Kashin-Beck disease. Inferences about chondronecrosis in several spontaneous and experimental arthropathies of other species may be relevant to the cause of Kashin-Beck disease and conceivably, too, banal osteoarthritis in man. PMID- 2187419 TI - Pulse methylprednisolone therapy in rheumatoid arthritis: unproved therapy, unjustified therapy, or effective adjunctive treatment? PMID- 2187420 TI - Iron chelation in rheumatoid arthritis: clinical and laboratory evaluation. PMID- 2187421 TI - Ethical decisions in the history of organ transplantation. PMID- 2187422 TI - Cardiac missiles. A review of the literature and personal experience. AB - The management of retained missiles in the heart is still controversial. In an attempt to define the issue more clearly, the reported cases in the English literature from 1940 to 1988 (group 1) and our experience from 1968 to 1988 (group 2) were reviewed. In group 1 there were 222 missiles retained in the hearts of 201 patients. The retained missiles were 45 bullets in 45 patients, 109 shrapnel in 99 patients, 18 pellets in 7 patients, and 50 unidentified missiles in 50 patients. Thirteen of the missiles were completely embedded intramyocardial missiles, 122 were partially intramyocardial, 47 were free in a cardiac chamber, and 40 were intrapericardial. One hundred four of the missiles were removed and 118 were left in place. In group 2 there were 24 missiles, 18 bullets, 1 bullet fragment, and 5 pellets retained in the hearts of 24 patients. Ten missiles were removed, no attempt was made in 13 patients, and an unsuccessful attempt was made to remove one other. From group 1 patients, 6 died, 2 with intracavitary missiles, 3 patients with partially intramyocardial, and 1 patient with an intrapericardial missile, all of whom had either unsuccessful or no attempt to remove the missile. Twenty-seven patients had symptoms, all of whom, except two, had either unsuccessful or no attempt to remove the missile. All group 2 patients did well and had been free of symptoms related to the missiles. This review suggests that the management of missiles in the heart should be individualized according to the patient's clinical course, the site, shape, and size of the missile, and that in selected patients missiles in the heart are tolerated well. PMID- 2187424 TI - Cystic pulmonary hamartoma. AB - A case of cystic pulmonary hamartoma is reported and the literature is reviewed. According to the literature, only 6 well-documented cases have been previously reported, and all the patients including our patient fared well after operation. PMID- 2187423 TI - Research and the practicing surgeon. PMID- 2187425 TI - Surgery for ventricular arrhythmia. AB - Years of frustration of cardiac surgeons attempting to control intractable ventricular arrhythmia finally ended when the team of Harken, Josephson, and Horowitz performed electrophysiologically directed left ventricular endocardial resection and reported their early results 10 years ago. The scientific background for this breakthrough is reviewed and some subsequent modifications of their procedure are described. The current status of arrhythmia surgery since the advent of the automatic internal cardioverter-defibrillator is described: the two methodologies are complementary, not competitive. PMID- 2187426 TI - Lung and heart-lung transplantation. AB - Unilateral lung transplantation has become a successful method for the treatment of end-stage pulmonary disease, whereas double-lung transplantation has provided benefit to patients with nonfibrotic lung disease such as emphysema and cystic fibrosis. In the past 5 years, 16 single-lung and 13 double-lung transplantations have been performed by the Toronto Lung Transplant Group in patients with end stage lung disease. Seven perioperative and two late deaths have been recorded so far. Since the introduction of heart-lung transplantation at Stanford in 1981 and at Pittsburgh in 1982 for the treatment of Eisenmenger's syndrome and terminal pulmonary vascular disease, more than 350 combined heart-lung transplantations have been carried out throughout the world. Presently, the 2-year actuarial survival is about 62%. The long-term results have not yet reached the same level of success as those of cardiac transplantation alone. Although several factors have played a role in this difference, a prominent cause has been the lack of a reliable and simple method for pulmonary protection against prolonged ischemia. Most of the techniques proposed against ischemia can be classified as normothermic or static hypothermic cardiopulmonary preservation. The use of the normothermic method has not always been successful. For this reason, interest has now been directed toward the potential for hypothermic preservation of the heart lung bloc and the use of free-radical scavenger therapy in the reduction of reperfusion injury. PMID- 2187427 TI - The trachea. PMID- 2187429 TI - Molecular mechanisms of cell transformation. PMID- 2187428 TI - Quantification of multiple-substrate controlled growth--simultaneous ammonium and glucose limitation in chemostat cultures of Klebsiella pneumoniae. AB - In chemostat cultures of Klebsiella pneumoniae (K. aerogenes) NCTC 418 we measured the concentrations of glucose and ammonium and we varied the ratio of the (limiting) concentrations of glucose and ammonium in the feed medium. By doing this at different dilution rates we found a range where growth rate varies with either concentration in the culture when the other concentration in the culture is held constant. This proves that within this range, dual-substrate controlled growth occurs. Dual substrate-controlled growth was accompanied by yield coefficients for glucose and for ammonium that were intermediate between the yield coefficients obtained for single glucose or single ammonium limitation. We quantified the control by either substrate in terms of the flux control coefficient with respect to that substrate, where flux refers to growth rate. Dual-substrate controlled growth is reflected by the finding that both flux control coefficients exceed zero, simultaneously. In the transition of glucose to ammonium limitation, the control gradually shifts from glucose to ammonium. PMID- 2187430 TI - Amplification of oncogenes and disease prognosis. AB - Amplification is one mechanism for activation of oncogenes and results in an excess of DNA template, which can lead to overproduction of oncogene-specific RNA and protein. Amplification of oncogenes has been observed in different tumor tissues. In certain cases amplification and overexpression of particular oncogenes have been correlated with tumor progression and clinical behavior. The best example is neuroblastoma in which the N-myc oncogene frequently is found to be amplified. Over 1,000 patients with breast cancer have been studied for amplification of the c-erbB-2 oncogene until now. The evidence from the studies that amplification of c-erbB-2 is correlated with poor prognosis is in our opinion not convincing. More and more investigations about oncogenes and disease prognosis will take place rather at the protein level than at the DNA level. PMID- 2187431 TI - New aspects of steroid hormone dependent tumor growth. AB - Steroids are able to modulate tumor growth. These mechanisms involve probably a complex network of events which earlier were thought to be rather independent of each other. This review summarizes some new results in steroid hormone research, concerning its influence in understanding of tumor growth, above all estrogen dependent mammary tumor growth. It focuses on the following main topics situated in the centre of research at present. 1. Steroid receptors triggering the biological action of steroids are members of a superfamily of transcriptional activators with potential growth modulating properties. The DNA-binding domain of these different proteins is highly conserved. Tumor cells possibly use some of these molecules for their own growth. 2. Hormone dependent mammary tumor growth includes probably a very complex interaction of steroids with their nuclear receptors, growth factors and their membrane receptors, proteolytic enzymes and others. Tumor cells are able to secrete a lot of different proteins in response to estradiol. PMID- 2187432 TI - Historical anecdotes concerning the early re-entry countermeasures with spaceflight. PMID- 2187433 TI - Long-term treatment of isolated rat soleus muscle with phorbol ester leads to loss of contraction-induced glucose transport. AB - Muscle contraction involves mobilization of intracellular Ca2+ and is associated with several metabolic adjustments, including increased glucose transport. In the present study isolated rat soleus muscles were exposed to 12-O tetradecanoylphorbol 13-acetate, and responses to both insulin and contraction in terms of glucose transport were assessed. Muscles treated with this phorbol ester for 12 h showed an increased basal rate of 3-O-methylglucose uptake, and responded partially to insulin but did not respond to contraction. Phorbol-ester treated and non-treated (vehicle-only) muscles were indistinguishable in terms of pre-contraction content of adenine nucleotide, phosphocreatine, lactate and glycogen, as well as contractile performance and contraction-induced glycogenolysis. Phorbol ester treatment of isolated solei for 12 h resulted in the loss of 90% of protein kinase C activity as determined with histone IIIs as substrate, and 70% as determined by using phorbol ester binding. It is concluded that treatment of solei with phorbol ester gives rise to a marked loss of contraction-induced glucose transport. PMID- 2187435 TI - Purification and characterization of the invertase from Schizosaccharomyces pombe. A comparative analysis with the invertase from Saccharomyces cerevisiae. AB - Invertase (EC 3.2.1.26) was purified to homogeneity from exponentially growing cells of Schizosaccharomyces pombe fully de-repressed for synthesis of the enzyme, and was shown to be a high-molecular-mass glycoprotein that can be dissociated in the presence of 8 M-urea/1% SDS into identical subunits with an apparent molecular mass of 205 kDa. The carbohydrate moiety, accounting for 67% of the total mass, is composed of equimolar amounts of mannose and galactose. There is a small amount of glucosamine, which is probably involved in the linkage to the protein moiety, since the enzyme is sensitive to treatment with endoglycosidase H. The composition of the carbohydrate moiety resembles that found in higher-eukaryotic glycoproteins and differs from glycoproteins found in Saccharomyces cerevisiae. The protein portion of each subunit is a polypeptide of molecular mass 60 kDa, very similar to the invertase of Sacch. cerevisiae. Both proteins cross-react with antibodies raised against the protein fractions of the other, indicating that the two enzymes are similar. PMID- 2187434 TI - Protein degradation in cultured fetal hepatocytes. Absence of an inhibitory effect of insulin. AB - The role of insulin to regulate protein turnover in fetal liver was investigated using primary cultures of fetal-rat hepatocytes. The basal rate of protein degradation (in the presence of insulin and amino acids) was the same in cultured fetal and adult hepatocytes (2.48 +/- 0.16 versus 2.46 +/- 0.06% of total protein degraded/h respectively). Incubation of cells in an unsupplemented media (without insulin or amino acids) resulted in a deprivation-induced increase in degradation in cells from both groups (P less than 0.05). Rates of proteolysis could be returned to their respective basal values by the addition of amino acids at 5 times their normal plasma concentrations. In adult cells, addition of insulin alone significantly inhibited protein degradation (P less than 0.05), whereas, in contrast, insulin was without effect on protein degradation in fetal hepatocytes. Both fetal and adults cells responded to dibutyryl cyclic AMP with an increase in protein degradation above that seen in the no-additions group. Results of experiments in which the effect of inhibitors of protein degradation (chloroquine, NH4Cl, amino acids and dinitrophenol) were tested suggested that lysosomes were responsible for 20-30% of total protein degradation in fetal hepatocytes. Impaired insulin processing in fetal hepatocytes was examined as a possible cause of the insulin-resistance in these cells. As determined by h.p.l.c. analysis, the same pattern of initial degradation products of insulin was found in fetal hepatocytes as had previously been found in adult hepatocytes. Incubation of cells with various doses of chloroquine resulted in an increase in cell-associated 125I-insulin and a decrease in insulin degradation in both fetal and adult cells. At the highest dose of chloroquine tested (500 microM), a slightly greater increase in insulin binding and a decrease in insulin degradation were observed in fetal cells as compared with adult cells. Rates of insulin internalization were also compared between fetal and adult cells. A 30% slower rate of insulin internalization was observed in fetal cells, as compared with adult cells. It was concluded that the absence of an effect of insulin on protein degradation in fetal hepatocytes is not the result of a major difference in insulin internalization and processing between fetal and adult hepatocytes. PMID- 2187436 TI - Characterization of Saccharomyces cerevisiae strains displaying high-level or low level resistance to trichothecene antibiotics. AB - Biochemical and genetic analyses have been carried out on Saccharomyces cerevisiae strains characterized in vivo as sensitive, low-level-resistant or high-level-resistant to trichothecene antibiotics. Levels of drug resistance in vitro were determined for each strain and for suitable diploids derived from them. Ribosome biogenesis was also studied in selected haploids. It is suggested that resistance in all cases results from a mutation in the gene encoding ribosomal protein L3. If this is indeed the situation, then different mutations in this same gene not only can cause low-level or high-level resistance to trichothecene antibiotics but also can affect the maturation of either 40 S or 60 S ribosomal subunits. PMID- 2187438 TI - Forty years of "drug research". PMID- 2187437 TI - Desensitization of prostaglandin F2 alpha-stimulated inositol phosphate generation in NIH-3T3 fibroblasts transformed by overexpression of normal c-Ha ras-1, c-Ki-ras-2 and c-N-ras genes. AB - The stimulation of inositol phosphate generation in control and ras-gene transformed NIH-3T3 cells by prostaglandin F2 alpha (PGF2 alpha) was investigated. Compared with the control cells, a desensitization of the response was observed in cells transformed by the overexpression of N-, Ha-, or Ki-ras genes. This desensitization was without effect upon the concentration causing half-maximal effect (EC50), dissociation constant (Kd) or number of PGF2 alpha receptors. Inhibition of PG synthesis was without effect upon desensitization, demonstrating that the effect was not agonist-induced. Desensitization could be induced in NIH-3T3 cells by culturing under conditions where the cells were all in the exponential growth phase, or by a 12 h exposure to a C-kinase-activating phorbol ester. These results suggest that desensitization of certain agonist induced inositol phospholipid responses in ras-transformed cells is a consequence of increased cell proliferation and associated amplification in C-kinase activity and is an indirect consequence of transformation by ras. PMID- 2187439 TI - Strategies in therapy and immunoprophylaxis of human immunodeficiency virus infection. AB - In designing antiviral drugs and therapeutic schemes some basic considerations should be taken into account: 1. RNA viruses and especially HIV (Human Immunodeficiency Virus) respond to environmental changes with evading mutations, hence, the high degree of variability of these viruses. All drugs interfering with viral functions will presumably give rise to resistant variants. 2. Approaches using cytotoxic peptides may induce adverse immune responses. Vaccines may elicit neutralizing antibodies, cellular cytotoxic responses, or both. The limitations of subunit vaccines or oligopeptides in eliciting cell mediated cytotoxicity in all vaccinees are outlined. Recent developments and the suitability of the SIV mac/rhesus monkey model are reviewed. The importance of adjuvants is indicated. PMID- 2187441 TI - Varicella with delayed contralateral hemiparesis detected by MRI. AB - We report a 3 1/2-year-old boy who developed a hemiparesis 4 weeks after the onset of a varicella infection. In previously described cases of varicella with delayed contralateral hemiparesis, computed tomography typically revealed infarcts in the basal ganglia and internal capsule. To our knowledge, our patient is the first studied by magnetic resonance imaging. The pathogenesis of this syndrome may be a varicella zoster virus-related vasculopathy similar to that observed in herpes zoster ophthalmicus with delayed contralateral hemiparesis. PMID- 2187440 TI - In vitro and in vivo experiments with the new inhibitor of mycobacterium leprae brodimoprim alone and in combination with dapsone. AB - The antibacterial effect of brodimoprim alone and in combination with dapsone has been studied in vitro in cell-free systems and in whole mycobacterial cells as well as in vivo in mice and humans. The obtained inhibitory effects in vitro and in vivo against model mycobacterial strains and M. leprae, the pharmacokinetic properties in human and its synergistic effect with the most used drug in the chemotherapy of leprosy, dapsone, make brodimoprim a promising candidate in the therapy of leprosy. PMID- 2187442 TI - Carnitine deficiency syndromes. AB - Carnitine deficiency syndromes manifest as metabolic encephalopathy, lipid storage myopathy, or cardiomyopathy. Impairment of long-chain fatty acid metabolism and failure of energy production affect tissues reliant on oxidative metabolism. The accumulation of toxic fatty acyl derivatives impedes gluconeogenesis and urea cycle function which, in turn, causes hypoketotic hypoglycemia, transaminase elevations, and hyperammonemia. Oxidation of accumulated fatty acids through an alternative pathway, omega-oxidation, produces dicarboxylic aciduria. Carnitine must be transported into skeletal muscle. Myopathic carnitine deficiency occurs when this transport mechanism is defective. Most systemic carnitine deficiencies are secondary to other disorders that promote excretion of carnitine as acylcarnitine; however, primary systemic carnitine deficiency, likely due to impaired renal conservation of carnitine, also occurs. PMID- 2187443 TI - [Monoclonal gammopathies in Tunisia]. AB - Protein electrophoresis and immunoelectrophoresis carried out on 4805 sera and 93 urine samples from Tunisian patients over 8 years, and a monoclonal protein was detected in 198 cases. The distribution of the monoclonal compounds to the clinical diagnosis was studied. 115 (58%) were classified as multiple myeloma (MK), 34 (17%) as alpha heavy chain disease (MCL a), 34 (17%) as monoclonal gammapathy associated to various diseases (GMOD), 11 (6%) as benign essential monoclonal gammapathies (GMBE), 4 (2%) as Waldenstrom's macroglobulinemia (MW). The relationship between the monoclonal immunoglobulin and the clinical diagnosis, the distribution of the monoclonal compounds according to the heavy chain class and the identification of the light chains were studied. The results obtained are in line with the principal data in literature concerning monoclonal gammapathy. However there is a particularity about monoclonal gammapathy observed in the Tunisian's population studied: Higher percentage of alpha heavy chain diseases, monoclonal IgD and monoclonal light chain. Lower percentage of monoclonal IgM in GMBE or GMOD, as in MW. PMID- 2187444 TI - [The interleukins: non-specific mediators of the immune response]. PMID- 2187445 TI - [Perioperative short-term preventive antibiotics in head-neck surgery]. AB - A prospective perioperative trial with cefotiam and metronidazol was carried out in 114 patients undergoing head and neck surgery. The patients were stratified in one group receiving a single-dose prophylaxis and a second group receiving a 24 hour prophylaxis. The postoperative complication rates were analysed depending on various risk factors and the size and duration of surgery. For operations of similar size the long term prophylaxis had no advantage over the one-dose prophylaxis. It is concluded that a one-dose prophylaxis appears sufficient in major head and neck cases. PMID- 2187446 TI - [Forensic evaluation of physical damage in the early Middle Ages--a comparison with current occupational disability guidelines]. AB - The legal systems of the Germanic tribes in the early Middle Ages elaborated detailed catalogs of forfeits in compensation for certain physical injuries. The perpetrator had to pay the forfeit to the injured person, or in case of manslaughter, to the tribe of the dead. By doing so he could avert the feud which otherwise faced him. These catalogs of forfeits exactly reflect the relative value that was appointed to certain parts of the body and to sensory functions. The catalog of the Lex Saxonum (c. 802), in which physical injuries are listed, ranging from loss of single phalanges, differentiated between thumb, forefinger, small finger, and the other fingers, to death, is compared with modern grades of disability. There are surprising parallels and interesting contrasts. Bilateral deafness is put on a level with bilateral blindness, the loss of both hands, both feet, both testicles, and death. PMID- 2187447 TI - [Microvascular palate replacement-plasty]. PMID- 2187448 TI - The specific treatment of emphysema. AB - Cigarette smoking is the major risk factor for development of emphysema. Many people are unable to stop smoking despite skilled support. The elastase antielastase imbalance hypothesis for the pathogenesis of emphysema suggests that treatment with a supplemental elastase inhibitor might prevent development of emphysema in susceptible people. Many elastase inhibitors have been developed. Poorly soluble inhibitors do not prevent emphysema when tested in an animal model of elastase-induced emphysema. Irreversible inhibitors are effective in a dose response manner. Reversible but tight-binding large molecular weight inhibitors, which clear slowly from the lungs, are effective in vivo. Small molecular weight, reversible inhibitors prevent haemorrhage after human neutrophil elastase instillation into the lungs but may potentiate emphysema. Only 15% of long-term smokers are susceptible to the development of emphysema. Susceptible smokers can be identified by the development of airflow obstruction. An outcome study of efficacy of elastase inhibitor therapy would be prohibitively expensive. However, a study of the process of development of elastase-induced emphysema is feasible. Measurement of alterations in elastase load of the lungs, elastase derived fibrinopeptides, circulating elastin peptides and urinary desmosines could be used for this purpose. PMID- 2187449 TI - [Hemostatic disorders in anesthesiology and surgical intensive care]. AB - Apart from straightforward haemorrhage, bleeding problems in anaesthesiology and intensive care are predominantly due to multifactorial haemostatic derangements caused by a depletion of procoagulant factors, inhibitors, and platelets. In certain settings, these events are complicated by an enhanced procoagulant and decreased fibrinolytic activity of the endothelium. This functional turnabout of the vasculature promotes disseminated intravascular coagulation (DIC). A rational therapeutic approach is based on estimates of the patient's losses and his volume of blood, adequate and repeated haemostatic monitoring, and an individually tailored substitution considering the critical levels of the informative parameters, i.e. the platelets, fibrinogen, Quick and aPTT, together with the haemostatic efficacy of the available preparations. Whenever possible, subclinical trends towards abnormal bleeding should be identified and countered by appropriate measures before an actual and potentially life-threatening haemostatic breakdown develops. PMID- 2187450 TI - Autoimmunity: a T-cell receptor perspective. PMID- 2187451 TI - Novel origin of lpr and gld cells and possible implications in autoimmunity. AB - The lpr and gld mutations are prime examples of single-gene defects associated with expansion of a unique double-negative (CD4-8-), T-cell receptor alpha:beta + cell population and heightened polyclonal and autoimmune responses. The exact origin of these autoimmunity-inducing/enhancing T cells remains controversial. Here, we review the characteristics of the lpr and gld mutations, and speculate on the possible relationship of these cells to normal thymic differentiation pathways. We argue that mounting evidence now supports the existence of a CD4/CD8 loss pathway of late thymic differentiation, responsible for the origin of both normal and lpr/gld double-negative alpha:beta + cells. We further speculate that downregulation of CD4 and CD8 accessory molecules on thymocytes with moderately autoreactive T-cell receptors is involved in selecting cells, including lpr/gld precursors for this pathway. Escape of a large number of such autoreactive cells from thymic elimination might be an important contributory factor to the pathogenesis of autoimmunity. PMID- 2187452 TI - Inappropriate major histocompatibility complex expression on cardiac tissue in dilated cardiomyopathy. Relevance for autoimmunity? AB - The inappropriate expression of major histocompatibility complex (MHC) molecules on epithelial and endothelial cells is a recognized marker of autoimmune disease. An autoimmune pathogenesis has been suspected in dilated cardiomyopathy (DCM). In the normal heart, MHC products are usually not detectable on myocytes using immunochemical techniques. MHC molecule expression has not, however, been assessed on cardiac endothelial cells. The aim of this study was to investigate possible autoimmune phenomena and MHC molecule expression in fresh endomyocardial biopsies from 29 patients with DCM. These were compared with those observed in surgical specimens from 63 patients with other acquired cardiac disease and from 22 with congenital heart disease (CHD) as normal controls. Conventional immunofluorescence (IFL) with monoclonal antibodies (MoAbs) to lymphocyte and macrophage markers and to MHC molecules was employed, and double IFL with antiserum to human Factor VIII was used for the identification of endothelial cells. Myocytes did not express MHC molecules in either DCM or controls. In normal hearts, Class II molecules were detected on endothelial and endocardial cells in only a few cases (3/22 and 2/22 respectively). By contrast, endothelial and endocardial cells inappropriately expressed Class II in a high proportion of DCM patients (28/29 and 22/29) but less frequently in other acquired cardiac diseases (19/63, P less than 0.001 and 11/63, P less than 0.001 respectively). In all the DCM biopsies examined there was a hierarchy of Class II subloci product expression (DR greater than DP greater than DQ); lymphocytic infiltration was a rare finding and macrophages/dendritic cells were not prominent. The finding of inappropriate MHC Class II molecule expression on cardiac endothelial and on endocardial cells suggests a possible pathogenic role for these cells in the initiation and/or perpetuation of DCM. PMID- 2187453 TI - Phagocyte oxidative metabolism in cyclosporine- or placebo-treated patients with insulin-dependent (type I) diabetes mellitus of recent onset. AB - Several lines of evidence suggest that phagocyte-mediated oxidative processes are involved in damage to pancreatic islet cells of Type I insulin-dependent diabetes mellitus (IDDM). This hypothesis, however, has not yet been explored at the clinical onset of IDDM. Similarly, the possibility that cyclosporine A (Cy-A) might exert a selective influence on these phagocyte-mediated oxidative reactions has also not yet been investigated as compared to a placebo. The present study tested both hypotheses in 32 patients with recently diagnosed IDDM who were part of the recent French multicenter randomized therapeutic trial of Cy-A. The production of reactive oxygen intermediates (ROI) by circulating polymorphonuclear (PMN) and mononuclear (MN) phagocytes was determined by luminol dependent chemiluminescence (CL), both directly within microamounts of whole blood and in purified PMN or MN phagocyte suspensions. Lastly, CL production was measured in the absence (resting CL) and the presence of a panel of particular and soluble phagocyte membrane-stimulating agents. We found that on entry into the trial, i.e. within less than 2 months of the clinical onset of IDDM, patients had normal whole blood CL production in the absence of a stimulating agent and upon phagocytic challenge with latex or opsonised zymosan particles. By contrast, whole blood CL responses to soluble stimuli such as phorbol myristate acetate (PMA), concanavalin A (Con-A) and F Met-Leu-Phe (FMLP) were significantly higher than in the control group of 52 normal subjects (P less than 0.01). In purified PMN and MN phagocyte suspensions, both resting and stimulated CL productions were normal, regardless of the type of stimulating agent. After 3 months of treatment, whole blood CL responses to Con-A and FMLP returned to almost normal levels in patients treated with Cy-A (15 cases) but not in those receiving the placebo (17 cases); PMA-induced CL responses were also decreased, but this was found in both groups of patients. In purified phagocyte suspensions we detected no effect of Cy A on PMN, whereas MN phagocytes from Cy-A-treated patients showed reduced CL responses to FMLP but not to other stimuli. Altogether, these results demonstrate for the first time that the capacity of circulating PMN and MN phagocytes to generate ROI is normal at the clinical onset of IDDM and suggest that circulating substances increase oxidative responses to soluble, but not particulate, stimuli.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2187454 TI - The involvement of Ly2+ T cells in beta cell destruction. AB - The non-obese diabetic (NOD) mouse is considered to be a good model of human Type I diabetes mellitus. Both sexes develop insulitis starting at about 6 weeks of age, and onset of diabetes follows at about 30 weeks in females, but later and much less frequently in males. In some mice (but not all) infiltration of the islets leads to selective destruction of insulin-producing beta cells, which is marked by clinically overt diabetes and is thought to be an autoimmune response mediated by T cells. Both L3T4+ and Ly2+ cells have been implicated in the destructive process and we have used an in vivo transfer system, together with histological studies on the pancreas, to demonstrate the essential role played by Ly2+ T cells in the destruction of beta cells in diabetic mice. PMID- 2187455 TI - Cytokine-mediated beta-cell destruction--the molecular effector mechanism causing IDDM? PMID- 2187456 TI - Persistent virus infection and development of virus-induced disease. PMID- 2187457 TI - Does viral infection initiate autoimmunity in type I diabetes? PMID- 2187458 TI - Genetic susceptibility to type I diabetes: a review. AB - There is evidence that Type I diabetes is a genetically and environmentally determined disease. Among the genetic influences the HLA system appears to play a dominant role. HLA-DQ has been strongly implicated as the primary responsible locus by the recent discovery that position 57 in the polymorphic first domain of the DQB chain appears to be a critical residue in conferring susceptibility. DQB products which contain the negatively charged amino acid aspartate at this position are protective while those containing the neutral valine, serine or alanine are susceptibility molecules. This discovery has served to explain, in a reductionist manner, some of the previously described HLA associations seen with diabetes. However, there are clear exceptions to the position 57 hypothesis which appears to explain some, but not all, of the HLA risk associated with this disease. Evidence is accumulating that the HLA contribution to diabetes susceptibility is heterogeneous, resulting in the identification of patient subgroups. When heterogeneity, revealed by studying non-HLA genes such as Gm, T cell receptor and interleukin, are superimposed on HLA genetic risk, further complexity is likely to arise. The definition of patient subgroups defined by genetic profiles will be required in order to study the contribution of environmental factors effectively. PMID- 2187460 TI - Comparison of islet autoantibodies in 'pre-diabetes' and recommendations for screening. PMID- 2187459 TI - The natural history and predictive value of Mr 64,000 autoantibodies for insulin dependent diabetes mellitus. PMID- 2187461 TI - Supratypes and ancestral haplotypes in IDDM: potential importance of central non HLA MHC genes. AB - Juvenile insulin-dependent diabetes mellitus develops in susceptible children exposed to unknown environmental factors. If the genes responsible for susceptibility could be identified, it should be possible to understand the method of injury to beta cells as well as identify the infectious or other agents involved. For a decade it has been known that one or more of the susceptibility genes must be within the major histocompatibility complex (MHC). Unfortunately, there are at least 20 different genes in the complex and it has not been possible to determine which are actually responsible. Therefore, we undertook to apply a new concept and new technology to the problem. Over several years we have shown that the diabetogenic gene(s) are contained within conserved ancestral haplotypes which can then be used as markers of the DNA which must contain the gene(s), whether present in a patient or an asymptomatic carrier such as a parent. This approach avoids the confusion which has resulted from using DR3 or DR4 which are only sometimes associated with the relevant genes. The new technology involves pulsed field gel electrophoresis which allows examination of large fragments of DNA containing all of the MHC, and makes it possible to identify deletions and duplications which were otherwise undetectable. In the first instance we compared two ancestral haplotypes [1,8,3 (8.1) and 18,F1,3 (18.2)] known to contain the relevant genes, and contrasted the DNA with that of another ancestral haplotype [3,7,2(7.1)] which is known to lack these genes. We have shown that there are three major deletions common to the two carrier haplotypes but absent in the protective haplotypes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2187462 TI - Type I diabetes: polygenic inheritance, multiple autoantigens and 'dual' parameter prediction. PMID- 2187463 TI - Ectopic class II MHC antigen expression and the development of diabetes. PMID- 2187464 TI - Tolerance and diabetes in transgenic mice over-expressing class I histocompatibility molecules in pancreatic beta cells. AB - The Class I gene, H-2Kb, was linked to the rat insulin promoter and the construct inoculated into fertilized mouse eggs to produce lines of transgenic mice. Mice which expressed the Class I molecule in the beta cells of the pancreas developed diabetes and progressive loss of their pancreatic beta cells. This occurred whether the transgene product was syngeneic or allogeneic with respect to its host. No lymphocytic infiltration was ever seen in transgene expressing mice, even in those deliberately immunized with H-2Kb-bearing cells. When the transgene product was allogeneic, spleen cells from the transgenic mice stimulated in vitro with irradiated B10.A(5R) cells (KbDd), could kill H-2d targets in vitro, but not targets bearing H-2Kb. Responsiveness of spleen cells to H-2Kb targets returned with advancing age, as the severity of diabetes increased. The results indicate that diabetes in this model occurs independently of the immune system, and point to an extra-thymic mechanism of tolerance induction dependent on the continuous presence of antigen. PMID- 2187465 TI - Hilton Head revisited--cytokine explosion of the 80s takes shape for the 90s. AB - The Second International Workshop on Cytokines was held two years after its predecessor. The scope was extremely broad--cytokines. This attracted a large and extremely diverse group of participants (700 people and 526 abstracts), interested in many different cytokines (interleukins 1-8, tumor necrosis factors, interferons, colony-stimulating factors, platelet-derived growth factor, fibroblast growth factors and others) from the perspective mainly of research laboratories devoted to studies of diverse disciplines such as immunology, endocrinology, neurobiology, molecular biology, pharmacology and biochemistry. PMID- 2187467 TI - Death and transfiguration of cortical thymocytes: a reconsideration. AB - The fate of most cells in the mammalian thymus, namely CD4+CD8+ (double positive) cortical cells, is unknown. A fraction of the cells in this population serve as developmental intermediates, but the vast majority will die. In this article Ellen Rothenberg discusses how and when the cells are condemned or promoted to maturity, in the light of intriguing new data that suggests that they may be able to be rescued for longer than was previously thought. PMID- 2187466 TI - An explanation of the variable clinical response to interleukin 2 and LAK cells. AB - Adoptive immunotherapy for the treatment of cancer has met with limited but, for some, encouraging success. A minority of malignant melanoma and renal cell carcinoma patients respond to therapy with interleukin 2 (IL-2) or IL-2 plus lymphokine-activated killer (LAK) cells. The mechanism of response, and the reasons for the variation within disease groups, is not clear. In this article, Giorgio Parmiani proposes that successful adoptive therapy is dependent on the recruitment of activated host antitumor T lymphocytes and suggests that this explains the greater efficacy of tumor-infiltrating lymphocytes in combating melanoma and renal cell carcinoma. PMID- 2187468 TI - Cellular signalling in programmed cell death (apoptosis). PMID- 2187469 TI - Genetic control of autoimmunity in type 1 diabetes. AB - DNA sequence analysis of major histocompatibility complex (MHC) class II genes from humans and rodents with type 1 (insulin-dependent) diabetes indicates that a portion of MHC-linked genetic susceptibility in humans is determined by the HLA DQA1 and -DQB1 loci. In this article John Todd summarizes recent advances in these studies. The conformation of DQ molecules and their levels of expression may influence the efficiency of autoantigen presentation and the degree of pancreatic beta cells destruction during disease development. Certain DAQ1 and DQB1 alleles correlate with decreased susceptibility to disease. The penetrance of class II alleles that are correlated with positive susceptibility may be influenced by environmental factors such as bacterial and viral infections. PMID- 2187470 TI - Heat shock proteins and the immune response. AB - Heat shock proteins (HSPs) or stress proteins are produced by prokaryotic and eukaryotic cells in response to a variety of insults. After this original definition, it has become increasingly clear that HSPs can modify the function and destiny of other proteins and thus play an important role in numerous physiological processes. The heat shock response is one of the most universal reactions known and HSPs are among the most conserved molecules in phylogeny. Here Stefan H.E. Kaufmann discusses the role of HSPs in immunity with respect to both their function and their antigenicity. PMID- 2187472 TI - [The first cases of asthma due to ragweed pollen in Maine-et-Loire and Vendee]. PMID- 2187471 TI - Guilt by association: HLA-B27 and ankylosing spondylitis. AB - The remarkable association between HLA-B27 and ankylosing spondylitis (AS) remains an enigma. While previous reviews have discussed the controversies surrounding the involvement of bacteria in the etiology of this disease and the sequence variability between subtypes of HLA-B27, concepts of disease mechanism remain ill-defined. In this article Richard Benjamin and Peter Parham synthesize new data on the structure and function of HLA class I molecules into possible mechanisms that might underly the pathogenesis of AS. PMID- 2187473 TI - [Mercury--is it a respiratory tract allergen?]. AB - Mercury is a well-known allergen in dermato-allergology, often manifesting as delayed type hypersensitivity contact eczema. Immediate hypersensitivity reactions (urticaria, anaphylactic shock) have also been described for this allergen, most frequently seen in patients with the delayed type contact eczema. To our knowledge this allergen has not been implicated in production of respiratory symptoms. We describe a patient who had aggravation of asthma by mercury contained in dental amalgam. When the dental amalgam was removed there was a great improvement in his asthma. This observation suggests that mercury in the form of dental amalgam may also be an allergen of the respiratory tract, which should not be surprising, bearing in mind the work that shows the existence of mercury vapours from dental amalgam. PMID- 2187474 TI - Crystallization of alcohol oxidase from Pichia pastoris. Secondary structure predictions indicate a domain with the eightfold beta/alpha-barrel fold. AB - Alcohol oxidase from Pichia pastoris has been crystallized from polyethylene glycol 4000 solutions. The crystals are tetragonal, a = 228 A, c = 456 A space group P4(1)2(1)2. The crystals scatter only to about 6 A resolution; their poor crystallinity may have some physiological function. Secondary structure predictions suggest that the C-terminal part of the molecule, residues 311-664, has the folding of an eightfold beta/alpha-barrel (TIM barrel). This would indicate common ancestry with four other flavoenzymes: canavalin, glycolate oxidase, flavocytochrome b, and trimethylamine dehydrogenase. PMID- 2187475 TI - Yeast-derived recombinant human insulin-like growth factor I: production, purification, and structural characterization. AB - Recombinant human insulin-like growth factor I (IGF-I) is efficiently expressed and secreted from Saccharomyces cerevisiae using a yeast alpha-factor leader to direct secretion. However, approximately 10-20% of the IGF-I was in a monomeric form, the remaining materials being disulfide-linked aggregates. When the purified material was subjected to reverse-phase high-performance liquid chromatography (rp-HPLC), it gave two doublet peaks, I and II. Upon reduction, doublet peaks I and II converged to one doublet peak. This suggests that peaks I and II result from different disulfide structures, and the doublet feature of each peak results from other causes. Different disulfide structures between peaks I and II were also suggested from the near UV circular dichroism of these proteins. Only the peak II was biologically active, indicating that peak II has the correct disulfide structure. Concanavalin A affinity chromatography of the purified peak II doublet showed binding of the subpeak with an earlier rp-HPLC retention time, indicating that it was glycosylated. Sequence analysis of tryptic peptides suggested that Thr29 was the site of glycosylation. Site-directed mutagenesis was used to convert Thr29 to Asn29. This substitution reduced, but did not eliminate IGF-I glycosylation, suggesting additional glycosylation sites. The site of carbohydrate addition was consistent with the model that O glycosylations occur on hydroxyl amino acids near proline residues in beta-turns. PMID- 2187476 TI - Sequential changes in epidermal growth factor receptor/ligand function in cultured rat liver epithelial cells transformed chemically in vitro. AB - Diploid WB rat liver epithelial cells contain abundant, rapidly internalized epidermal growth factor receptors, and respond pleiotropically to ligand binding. Signal transduction pathways downstream from the EGF receptor involve activation of elements that are both dependent on and independent of protein kinase C activation. Neoplastic transformation of wild-type WB rat liver epithelial cells by exposure to N-methyl-N'-nitro-N-nitrosoguanidine is associated with progressive alterations in the responses of affected cells to binding of EGF to EGF receptors, including heightened cell proliferation and the expression of several other phenotypic properties. Tumorigenic rat liver epithelial cells acquire the ability to express transforming growth factor-alpha (TGF-alpha), and to secrete this growth factor in a regulated and then unregulated manner. TGF alpha expression, together with the presence of abundant EGF receptors, provides affected cells with an autocrine growth cycle. The ability of transformed WB rat liver epithelial cells to produce tumors cosegregates clonally with TGF-alpha expression and with heightened expression of c-myc, c-Ha-ras and c-Ki-ras proto oncogenes. PMID- 2187477 TI - Differentiation and cell proliferation patterns in rat exocrine pancreas: role of type I and type II injury. AB - Fully differentiated and functionally specialized acinar cells of the rat pancreas are versatile and adaptable. Acinar cells can be stimulated to divide following administration of a mitogen or after inducing acinar cell necrosis. The degree of compensatory hyperplasia is dependent upon the extent of acinar cell necrosis. Type I injury (subtotal acinar cell necrosis) is followed by marked proliferation of acinar cells leading to complete restitution of the pancreas, whereas subsequent to type II injury (global acinar cell necrosis) there is no restitution of the pancreas because of lack of enough viable cells that have served as precursor cells. Associated with type Ii injury there is proliferation of ductular and periductular cells followed by the development of hepatocytes. In addition, during adverse conditions acinar cells undergo dedifferentiation and form pseudoductular structures. In rats, acinar tissue is a prime target for carcinogens. Transformed acinar cells form foci which are morphologically classified as acidophilic and basophilic lesions. Acidophilic foci which show increased cell proliferation progress to form nodules and acinar cell carcinomas. PMID- 2187478 TI - Isolation, culture, and transplantation of intrahepatic biliary epithelial cells and oval cells. AB - Recent advances made in the isolation, culture, and transplantation of defined populations of intrahepatic biliary epithelial cells and oval cells have permitted direct analysis of the functions, growth properties, and differentiation potential of these respective cell types in their untransformed or transformed states. This review provides a current and comprehensive examination of the various approaches that have been taken to isolate and culture intrahepatic biliary epithelial cells from normal and cholestatic liver and oval cells from preneoplastic liver. Emphasis is placed on comparing the phenotypic features and growth properties of these various biliary cell types in vitro as well as on describing their transplantation into ectopic tissue sites. In addition, the oval cell is evaluated in terms of its potential role as a 'facultative stem cell' during hepatocarcinogenesis. PMID- 2187479 TI - Escherichia coli expression and processing of human interleukin-1 beta fused to signal peptides. AB - Escherichia coli expression, processing, and secretion of human interleukin-1 beta (IL-1 beta) fused to the signal peptide of E. coli OmpA or PhoA protein were studied. With fusion to either signal sequence, high-level expression was observed and the products accumulated to about 20% of total cell protein. In the fusion to OmpA leader sequence, more than 50% of the product has the OmpA signal peptide removed precisely. The majority of the processed material is not released by osmotic shock. On the other hand, very little of the material from the fusion to PhoA has the PhoA signal peptide removed. Use of the host with a mutation in prlA or prlF, variation of temperature for cell growth, and alteration of the amino acid residues around the cleavage site do not facilitate processing of the PhoA signal peptide. These results suggest that some component in the PhoA signal peptide, interacting with the Il-1 beta sequence, is interfering with the processing of the signal peptide. PMID- 2187480 TI - Efficient transfection and expression of heterologous genes in PC12 cells. AB - The PC12 pheochromocytoma cell line has been a favorite model system for cell and neurobiologists, but has proven relatively refractory to standard DNA transfection methods. We have found that the cationic lipid "lipofectin" provides a simple, gentle, and nontoxic procedure that vastly improves transfection efficiencies in PC12 cells. Transient expression of chloramphenicol acetyl transferase (CAT) driven by a Rous sarcoma virus long terminal repeat (LTR) is much more efficient using lipofectin when compared with calcium phosphate as a transfection procedure. Additionally, transient transfection of nerve growth factor (NGF)-differentiated PC12 cells proceeds with equal efficiency relative to naive, uninduced cells. Using the lipofectin procedure, the frequency of stable transfection is 100-fold higher than that reported with standard calcium phosphate precipitation protocols. To examine the effectiveness of different promoters for efficient expression of heterologous DNA in PC12 cells, three different promoter-bearing constructs were utilized. Each construct contains a different promoter sequence upstream from a chicken calsequestrin cDNA. A human cytomegalovirus (CMV) immediate early promoter construct produced the highest level of expression, followed by a human beta-actin promoter construct. Expression from a mouse Moloney sarcoma virus LTR construct could not be detected. These results overcome the previous transfection problems of low efficiency and low viability that have plagued many PC12 cell investigations. PMID- 2187481 TI - Sensory irritant receptor compartment properties. Equipotent vapour concentrations related to saturated vapour concentrations, octanol-water, and octanol-gas partition coefficients. AB - Receptor compartments can be hydrophilic or hydrophobic. The hydrophobic character can be revealed from the logarithmic relationship between the octanol water partition coefficient (Po/w) and the equipotent equilibrium concentration (Cw) measured in the water compartment (Franke: Theoretical Drug Design Methods. Elsevier, Amsterdam 1984). For activation of the sensory irritant receptor during exposure to airborne chemicals the Cw values at equilibrium can be obtained from the gas or vapour concentrations [( A]a) and the water-gas partition coefficients (Pw/g). However, if the octanol-gas partition coefficients (Po/g) are used, the analysis can be carried out directly from the gas or vapour concentrations. The thermodynamic activity can also be used to reveal whether the environment of the receptor is hydrophobic or not. We have adapted Franke's theory to a series of homologous airborne sensory irritants. Our results suggest that the environment of the sensory irritant receptor is likely to be a hydrophobic site within the polar part of the nerve membrane. The extended theory is general and it is therefore suggested that it applies to other airborne exposure concentrations which are in equilibrium with a hydrophobic receptor. PMID- 2187482 TI - Ernst Klenk lecture, November 1989. The complexities of intracellular Ca2+ signalling. PMID- 2187484 TI - Substance immunologically cross-reactive with insulin from murine myeloid leukemia: purification and characterization. AB - A substance immunologically cross-reactive with insulin (SICRI) appears in murine myeloid leukemia. Progression of disease is paralleled by the increase of SICRI levels in the serum; this increase of SICRI levels did not correlate with a decreased concentration of circulating glucose. SICRI was isolated and purified from spleen infiltrated with leukemic cells. Monospecific antiinsulin immunoglobulin G was used for immunoaffinity chromatography to isolate SICRI from tumor tissue. The purified substance yielded a single band with a molecular mass of about 150 kDa in polyacrylamide gel electrophoresis under denaturating and non denaturating conditions. Purified SICRI enhanced growth of myeloid leukemia cells in soft agar. Biochemical and biological data together with our previous results obtained in other experimental tumors provide evidence that SICRI and insulin are two distinct biologically active agents. SICRI plays a role in murine myeloid leukemia as an autocrine growth promoting factor. PMID- 2187483 TI - Expression of the E. coli nadB gene and characterization of the gene product L aspartate oxidase. AB - Quinolinic acid is synthesized in E. coli by the enzymes L-aspartate oxidase and quinolinate synthase A, the genes of which are named nadB and nadA. In our previous work we cloned and characterized the two genes (Flachmann, R., Kunz, N., Seifert, J., Gutlich, M., Wientjes, F.J., Laufer, A. & Gassen, H.G. (1988) Eur. J. Biochem. 175, 221-228). Here we report on the expression of the nadB gene under control of the inducible left promoter of the bacteriophage lambda. The yield of the active gene product L-aspartate oxidase was enhanced up to 20% of the soluble cell protein. The enzyme was purified to homogeneity in a three-step procedure and the reading frame of the L-aspartate oxidase gene was confirmed by Edman degradation of five cyanogen bromide peptides. L-Aspartate oxidase shows no classical Michaelis-Menten behaviour but is subject to a substrate inactivation. The apparent Km values were different for substrate concentrations below and above 1mM and were determined to 0.5 mM and 4.1mM, respectively. The active form of the enzyme is a monomer of 60,284 Da and contains one molecule of FAD and nine cysteine residues, four of which built up two disulfide bonds. The isoelectric point of the protein was determined to be at pH 5.6. Chemical modifications of the enzyme showed that at least one tyrosine and one histidine residue are essential for enzyme activity. The coenzyme-binding domain is located in the amino-terminal part of the polypeptide chain as revealed by a sequence comparison to other dinucleotide binding enzymes. Furthermore, there is evidence for a relationship to fumarate reductase and succinate dehydrogenase of E. coli. PMID- 2187485 TI - Purification, assay and kinetic features of HIV-1 proteinase. AB - 1) The aspartic proteinase of the human immunodeficiency virus type 1 (HIV-1) was purified from cultures of recombinant E. coli. The enzyme preparation is homogeneous as judged by SDS-polyacrylamide gel electrophoresis and isoelectric focusing. 2) A rapid assay procedure for the proteinase was established which makes use of the cleavage of a radiolabeled decapeptide and the separation of substrate and labeled product by ion-exchange resin. 3) Activity of the enzyme is optimal at an ionic strength of 2.5-3.5M; also, the inhibitor pepstatin is a more potent inhibitor at higher ionic strength. This can be attributed to a tighter binding of both substrate and inhibitor in high-salt buffer. 4) The Km value of the decapeptide substrate is independent of the pH in the range of 3.5-7.5, while kcat shows a bell-shaped curve with a maximum at pH 5.2. The shape of the curve can be attributed to pKa values of 4.2 and 6.2 of groups on the enzyme. Pepstatin inhibition is optimal below pH 5.5, but becomes weak above pH 6. PMID- 2187486 TI - The beneficial effect of methylprednisolone in acute vestibular vertigo. AB - To assess the efficacy of corticosteroids in acute vestibular vertigo, we randomly selected 20 patients so that half took methylprednisolone and half took placebo. Extensive neurotologic examination confirmed the diagnosis. If no significant reduction of vertigo occurred within the first 24 hours of treatment, patients were instructed to switch medications. Patients were followed up prospectively for 1 month. Of the 10 patients receiving methylprednisolone, 9 had a marked reduction of vertiginous symptoms and 1 switched to the placebo medication. Of the 10 patients receiving placebo, 3 had relief of vertiginous symptoms, while the 7 with persistent symptoms switched to methylprednisolone and had subsequent effective reduction of vertigo within 24 hours. The electronystagmogram returned to normal within 1 month in all 16 patients taking methylprednisolone, but remained abnormal in 2 of the 4 patients treated with placebo. One patient receiving methylprednisolone had a relapse of symptoms when the dosage was tapered, but symptoms again remitted when the dosage was increased to 32 mg/d. From this double-blind, prospective, placebo-controlled, crossover study, we conclude that methylprednisolone is much more effective than placebo in reducing vertiginous symptoms in patients with acute vestibular vertigo. PMID- 2187487 TI - Submental W-plasty for correction of 'turkey gobbler' deformities. AB - There are many causes and types of submental contour deformities. One such deformity called a turkey gobbler, is caused by an excess of flaccid submental skin and as an isolated defect is seen more commonly in men. We have found that skin excision and a running submental W-plasty for correction of this deformity yields a superior cosmetic result with excellent camouflage of the submental scar. Two cases are illustrated. PMID- 2187488 TI - Response prompting and fading methods: a review. AB - Teachers of individuals with severe handicaps typically use response prompts, such as verbal instructions, modeling, and physical guidance, to encourage correct responding. However, the goal of instruction is to have the individual respond to natural stimuli rather than response prompts. Therefore, these response prompts must be faded. Currently there are four methods for systematically fading response prompts: increasing assistance, decreasing assistance, graduated guidance, and time delay. An overview of each method as well as a review of comparative investigations involving these methods of fading response prompts was presented. Recommendations for practitioners and for future research were included. PMID- 2187489 TI - Tropoelastin heterogeneity: implications for protein function and disease. AB - The organization of the tropoelastin gene is similar to that of other genes coding for matrix proteins in that the exons code for distinct domains of the protein. An unusual feature of tropoelastin expression is that the primary transcript of the gene coding for tropoelastin undergoes extensive, developmentally regulated alternative splicing, resulting in numerous protein isoforms. Although the significance of this heterogeneity is unknown, the multiple sequence variations may affect the function of tropoelastin. Without an understanding of the importance of the domains of tropoelastin and the process of fibrillogenesis, characterization of defects resulting in aberrant elastin production will be hindered. In this update, we review recent findings on tropoelastin and speculate as to the structural and regulatory role of various regions of this matrix protein. PMID- 2187490 TI - Endothelial cell proteoglycans: possible mediators of vascular responses to injury. PMID- 2187491 TI - Host epithelial glycoconjugates and pathogenic bacteria. PMID- 2187492 TI - Protease inhibitors potentiate smooth muscle relaxation induced by vasoactive intestinal peptide in isolated human bronchi. AB - To examine the role of endogenous proteases in limiting the bronchodilating effects of vasoactive intestinal peptide (VIP) in human airway, we studied precontracted bronchial rings from five nonsmokers undergoing heart-lung transplantation for pulmonary hypertension, either primary or secondary to congenital heart disease. The protease inhibitors aprotinin, leupeptin, phosphoramidon, and soybean trypsin inhibitors significantly potentiated the bronchodilator response to VIP. Even in the presence of the four protease inhibitors, VIP-induced bronchodilation reversed spontaneously in some tissues. These studies show that degradation by endogenous airway proteases is an important determinant of the bronchodilating potency of VIP in isolated human airway. PMID- 2187493 TI - Immunocytochemically detectable TGF-beta associated with malignancy in thyroid epithelial neoplasia. AB - The possible role of changes in TGF-beta expression in the multistage development of thyroid cancer was assessed. The presence of TGF-beta 1 in thyroid epithelial cells was analyzed in sections of normal and tumor tissue using an immunoperoxidase technique employing an antibody directed against the amino terminal 30 amino acids of mature TGF-beta 1. Specific immunostaining was clearly detected in epithelial cells in 58% of malignant thyroid tumours (including follicular, papillary, and anaplastic variants). However, no positive cells were seen in any of 7 benign tumors nor in any normal thyroid epithelium. Within the cancer group as a whole, there was no significant correlation with pathological grade or clinical stage of tumor but in one subgroup--follicular carcinomas--a significant association was noted between TGF-beta immunostaining and the presence of a specific mutation of the H-ras oncogene (codon 61, gln----arg). We conclude that a major alteration in expression of TGF-beta occurs specifically in the malignant stage of tumor development in thyroid follicular epithelium and speculate on its possible role in this process. PMID- 2187494 TI - Cytokines and growth regulation of synoviocytes from patients with rheumatoid arthritis and rats with streptococcal cell wall arthritis. AB - Paracrine growth factors probably stimulate the pathologic proliferation of synovial fibroblast-like cells (synoviocytes) in rheumatoid arthritis (RA), but the relative importance of various factors is highly controversial. To address this problem, we compared the effects of highly purified or recombinant cytokines, in serum-free medium, on the in vitro long-term growth of synoviocytes from patients with RA and rats with streptococcal cell wall (SCW) arthritis. Of the factors tested (PDGF, aFGF, bFGF, EGF, TGF-beta, IL-1-alpha, TNF-alpha and IFN-gamma), PDGF, was clearly the most potent stimulant of long-term growth of both rat and human synoviocytes. The strong mitogenic activity of rheumatoid synovial fluids was significantly inhibited by neutralizing anti-PDGF antibody, thus confirming the importance of PDGF. EGF, TGF-beta, IL-1-alpha, TNF-alpha, and IFN-gamma had minimal effects. Similar to the effects on anchorage-independent growth, TGF-beta 1 and 2, inhibited serum- or PDGF-stimulated anchorage-dependent growth. Considered in the context of other reports, these data support the view that cytokines such as PDGF, and possibly aFGF and bFGF, play major roles in stimulating synoviocyte hyperplasia in RA and SCW arthritis, whereas TGF-beta may inhibit synoviocyte growth. PMID- 2187495 TI - Evidence for a low-affinity interleukin-3 receptor. AB - Interleukin-3 (IL-3) regulates the proliferation of myeloid, erythroid, and lymphoid cells. Previous reports showed IL-3 binding restricted to a single high affinity (Kd = 50-200 pM) site. Here, we demonstrate by equilibrium studies an additional binding site for IL-3 with lower apparent affinity (Kd = 5-20 nM). Furthermore, kinetic analysis shows that two binding sites for IL-3 exist: IL-3 dissociates slowly from the first site (T1/2 = 4 hr; k-1 = 2.7 x 10(-3) min-1), whereas it dissociates rapidly (T1/2 = 4.0 min; k-1 = 0.116 min-1) from the second site. Cross-linking showed that [125I]IL-3 binding to the 115- and 140-kD proteins was not saturable at concentrations commensurate with high-affinity binding and IL-3 dissociated rapidly from these same molecules. Thus, the low affinity IL-3 receptor is a molecule(s) of 115- to 140-kD. PMID- 2187496 TI - Significance of increased efforts to gain participation in screening for breast cancer. AB - With increasing evidence of the effectiveness of mass screening in reducing mortality from breast cancer, the Breast Cancer Screening Study of the Health Insurance Plan of Greater New York is reviewed for its impact on increased efforts to gain participation among its target population. Initial contact efforts brought a 47% response rate, and further efforts increased this to 65%. The additional contact efforts increased response rates among most demographic groups. Women requiring minimum contact efforts were appreciably more likely than the increased effort group to participate in the full set of four screenings. Among those requiring increased efforts, more than 40% had the full set of screening examinations, and about 80% had at least one screening examination in addition to the baseline. Differences in breast cancer detection rates among contact effort groups were small, and there was little difference in mortality from breast cancer. Mortality rates from other causes, however, were higher among reluctant participants and highest among women who refused screening. Efforts to increase participation in screening for breast cancer should be linked to women's concerns with other health problems and to their medical care system. PMID- 2187497 TI - The role of thorium in endomyocardial fibrosis. AB - The behaviour of thorium in animals exposed through injection, ingestion and inhalation, as well as in uranium miners, millers and the general population suggests that thorium accumulates primarily in the lung, tracheobronchial lymph nodes and skeleton; or in the liver if injected with polymeric thorium. Epidemiological studies on uranium miners, Thorotrast studies in man and animal, and studies on the toxic effects of thorium in animals suggest that there is no apparent heart diseases due to exposure to thorium in man and animal. PMID- 2187498 TI - Variable proteolytic cleavage of gag precursor expressed after infection of several cell lines with an HIV-2 gag-pol recombinant vaccinia virus. PMID- 2187499 TI - Localization of B-cell stimulatory activity of HIV-1 to the carboxyl terminus of gp41. AB - Patients with AIDS are known to have B-cell hyperactivity. We have previously demonstrated that an extract of HIV-1 could induce differentiation of peripheral blood B lymphocytes of healthy volunteers into immunoglobulin-secreting cells. In an attempt to delineate the B-cell stimulatory subregion in HIV-1, we have investigated the influences of native glycoproteins and recombinant proteins of the envelope. The complete envelope glycoprotein, gp160 and a recombinant protein in the carboxyl terminal region of gp41 termed PE-8 were effective in inducing terminal differentiation of normal peripheral blood B lymphocytes and did so in a T-lymphocyte-dependent manner. The activity was not present in the native exterior envelope glycoprotein, gp120 and several other recombinant proteins, viz PE-2 an PE-3, which are in the amino terminal region of gp120 or in env-9, a protein in the junctional region of gp120 and gp41. Polyclonal and monoclonal antibodies directed to diverse regions of the envelope abrogated the influence of gp160. The PE-8-induced B-cell differentiation was abrogated by goat anti-gp160 antibody but not by goat anti-gp120 antibody or monoclonal antibody to the amino terminal of gp41. These studies suggest that a putative polyclonal B-cell stimulatory epitope of HIV-1 is located in the carboxyl end of the envelope glycoprotein. PMID- 2187500 TI - Characterization of the secreted, native gp120 and gp160 of the human immunodeficiency virus type 1. AB - We have previously shown that the cell line 6D5(451) chronically infected with the HIV-1 isolate HTLV-III(451), secretes the HIV-1 envelope glycoproteins gp120 and gp160 in the extracellular medium. The HTLV-III(451) gp120 and gp160 were purified by sequential affinity chromatographic steps using a monoclonal antibody to HIV-1 gp41 and an anti-HIV-1-positive human serum. Amino acid sequence analysis of gp120 and gp160 showed the loss of the signal peptide. Digestion of the purified gp120 and gp160 with endoglycosidases revealed that both proteins are heavily glycosylated and contain complex carbohydrates, in contrast to the intracellular form of gp160 which has been shown to contain mannose-rich immature sugars. Competitive binding analysis showed that while both gp120 and gp160 bind CD4, the affinity of gp160 was five times lower than that of gp120. Both gp120 and gp160 inhibited syncytia formation by HIV-1-infected cells when mixed with CD4+ cells. Furthermore, both gp120 and gp160 had strong mitogenic effects on the T cells from HIV-1-infected gibbons but not on cells from uninfected gibbons. PMID- 2187501 TI - Escherichia coli expression, purification, and biological activity of a truncated soluble CD4. AB - A truncated molecule containing the N-terminal 183 amino acid residues of CD4 (sCD4-183) has been produced in Escherichia coli at high levels, using the trp promoter and an AT-rich ribosome binding site to direct expression in a pBR322 derived vector. A culture has been selected which allows large-scale fermentation and production of this material as an insoluble inclusion body protein. Procedures which solubilize, refold, and purify sCD4-183 have been developed. The purified sCD4-183 binds gp120 in solution and blocks human immunodeficiency virus (HIV) infection of human peripheral blood lymphocytes in vitro. PMID- 2187502 TI - Bacterially produced HIV-2 env polypeptides specific for distinguishing HIV-2 from HIV-1 infections. AB - Five unique recombinant polypeptides, each encoded by a DNA segment representing a different region of the HIV-2 (NIH-Z strain) env gene, were produced at relatively high levels (greater than or equal to 5%) as cII-fusion products in Escherichia coli. These recombinant polypeptides were characterized serologically by the Western blot assay against a panel of HIV-2 and HIV-1 antibody-positive sera, and with normal human sera (HIV-1 and HIV-2 antibody negative). Only those polypeptides that are encoded by a segment of the env gene from the N-terminal region of the transmembrane protein gp35 (amino acids 537 to 707) were immunoreactive. Three polypeptides (921, 996, and 997), each encoding this immunoreactive region of the HIV-2 (NIH-Z) gp35, reacted strongly and specifically with antibodies in sera from HIV-2-positive individuals, but not with antibodies in sera from HIV-1-positive or HIV-uninfected individuals. These results show that the N-terminal region of the HIV-2 gp35 contains a highly antigenic determinant which is strongly immunogenic in HIV-2-infected individuals. The gp35-encoded recombinant env polypeptides can potentially be used in diagnostic assays to specifically differentiate between HIV-2 and HIV-1 infections. PMID- 2187503 TI - Lymphoproliferative responses to mitogens and HIV-1 envelope glycoprotein among volunteers vaccinated with recombinant gp160. AB - The protective immune response to human immunodeficiency virus type 1 (HIV-1) induced by vaccination will likely include cellular immune responses. We measured lymphoproliferative responses in persons vaccinated with a baculovirus-derived recombinant gp160 candidate AIDS vaccine. Twelve volunteers received either 40 micrograms of rgp160, 80 micrograms of rgp160, hepatitis B vaccine, or alum adjuvant alone on days 0, 30, and 180. Peripheral blood lymphocytes were collected on days 0, 28, 60, 120, 210, and 270 and were cryopreserved. Lymphocyte proliferation to mitogens and rgp160 with and without interleukin-2 stimulation were determined, and lymphokine production and antibody synthesis were measured. All vaccinees responded normally to stimulation with phytohemagglutinin and concanavalin A. One of 3 vaccinees who received 40 micrograms of rgp160, 2 of 2 vaccinees who received 80 micrograms of rgp160, and no controls developed rgp160 specific lymphoproliferative responses. No differences in the production of lymphokines (interleukin-2 and interferon-gamma) after stimulation with mitogens or rgp160 were found when rgp160 vaccinees and controls were compared. We conclude that rgp160 candidate vaccine induces antigen-specific lymphoproliferative responses in humans and does not interfere with immunocompetence as measured by in vitro responses to mitogen stimulation. PMID- 2187504 TI - A simple Escherichia coli system for monitoring HIV protease activity: analysis of two temperature-sensitive protease mutants. AB - A simple Escherichia coli system has been developed for the detection of human immunodeficiency virus (HIV) protease activity. In this system, the protease sequence is placed downstream of the HIV gag polypeptide in an operon arrangement. Upon expression of the operon, gag serves as the substrate for the protease; the level of protease activity can be determined by measurement of the cleavage product of gag in cell extracts by Western immunoblotting. This system is useful in both detection of protease mutations generated by mutagenesis and in testing substrate specificity of the protease by mutagenesis of the gag sequence. Using this system, we have observed that modification of the N-terminus of HIV protease renders the enzyme temperature sensitive; the temperature sensitivity is made more pronounced by the conserved change of valine to isoleucine at residue eleven. PMID- 2187505 TI - High prevalence of HTLV-II among intravenous drug abusers: PCR confirmation and typing. AB - The polymerase chain reaction (PCR) was used to confirm the presence of human T cell lymphotropic viruses (HTLV) in intravenous drug users (IVDU) whose sera were reactive by immunofluorescence assay (IFA) for HTLV-1/-II antibody. Peripheral blood mononuclear cells from 41 IFA-positive and 19 IFA-negative individuals were analyzed. HTLV sequences were detected in 39/41 IFA-positive samples; 36 were HTLV-II positive and 3 were HTLV-I positive. Two IFA antibody-positives were negative by both PCR and by enzyme immunoassay (EIA). One IFA and EIA antibody negative sample was positive for HTLV-II by PCR. This study indicates a high prevalence of HTLV-II among IVDUs and further demonstrates the feasibility of using PCR to differentiate between HTLV-I and -II. PMID- 2187506 TI - An intraperitoneal insulin regimen for diabetics on continuous cyclic peritoneal dialysis. AB - Intraperitoneal insulin requirements were evaluated in six diabetic patients who were switched from continuous ambulatory peritoneal dialysis to continuous cyclic peritoneal dialysis. The mean total daily intraperitoneal insulin dose on continuous cyclic peritoneal dialysis was 85% of the mean dose on continuous ambulatory peritoneal dialysis (66 +/- 33 vs. 78 +/- 47 units/day, respectively, not significant), with comparable glycemic control. Twenty-five to 58% (mean value, 41%) of the total daily intraperitoneal insulin was administered in the diurnal exchange of the patients on continuous cyclic peritoneal dialysis. The ratio of the total intraperitoneal insulin dose on continuous cyclic peritoneal dialysis to the subcutaneous insulin dose predialysis was between 1.2 and 2.4 (mean value, 1.9). As guidelines for converting intraperitoneal insulin doses for patients switched from continuous ambulatory peritoneal dialysis to continuous cyclic peritoneal dialysis, we recommend starting continuous cyclic peritoneal dialysis with a total daily insulin dose 15% less than the continuous ambulatory peritoneal dialysis dose and giving approximately 40% of the total daily insulin dose in the diurnal exchange. PMID- 2187507 TI - The peritoneovenous shunt. Inception to maturity. PMID- 2187509 TI - Maintenance of normoglycemia in pancreatectomized dogs with a controlled release micropump. AB - A diffusion-based insulin micropump was capable of sustaining normoglycemia in diabetic, pancreatectomized dogs for as long as 10 months. Basal insulin delivery was provided by diffusion into the peritoneal cavity from the insulin reservoir across a silicone rubber porous outlet, while the delivery of insulin was augmented for 35 minutes at mealtimes by repeated squeezing of a polyurethane foam disk; the latter was initiated 15 minutes prior to the start of the meal. In the best implant, which functioned for more than 10 months before it was deliberately terminated, the mean glucose level was 126 +/- 24.7 mg/dl (+/- SD) and the mean Schlichtkrull M value was 2.8. In the other three implants, the mean and standard deviations were a little higher. The basal insulin supply was sufficient to restore normoglycemia each morning, while the augmented supply substantially reduced the size of the postprandial period of hyperglycemia. Over the 10 month period studied, the maximum concentration was 150 mg/dl approximately 6 hours after the beginning of the meal, based on the mean of the approximately 200 glucose profiles determined for this implant. Despite this ability to maintain reasonable normoglycemic profiles for long periods, the pump performance deteriorated over this time period, presumably from a tissue reaction to the porous outlet of the implant. This deterioration was evident in the higher levels of glycemia associated with an insulin delivery program that was maintained for too long or in the need to readjust the program to achieve similar levels of glycemia. Nevertheless, the biocompatibility and efficacy of the controlled release micropump demonstrates the feasibility of this approach. PMID- 2187508 TI - Determining ultrafiltration properties of the peritoneum. AB - Peritoneal solute reflection coefficients have previously been determined by simply comparing the time dependence of the solute concentration in the dialysis solution with that predicted by mathematical models. The present study theoretically examines the experimental conditions required to determine the solute reflection coefficient from the dependence of the dialysate concentration on time. Optimal experimental conditions are first derived using an approximate mathematical model that permits simple interpretation; these predictions are confirmed by numerical computation using a more rigorous model. It is demonstrated that the peritoneal solute reflection coefficient can be determined when solute transport is in the blood to dialysate direction only during a hypertonic exchange. When solute transport is in the dialysate to blood direction, the solute reflection coefficient can be determined using a hypotonic dialysis solution only for solutes that diffuse slowly across the peritoneum. Reliable determinations of the peritoneal solute reflection coefficient can only be obtained when using these experimental conditions. PMID- 2187510 TI - Intra-arterial DSA and duplex-Doppler ultrasonography in detection of vascularized inguinal lymph node. AB - Twenty-three patients with ischemic disease of the legs referred for routine preoperative angiography were examined with intra-arterial DSA and high resolution ultrasonography with duplex-Doppler to detect inguinal lymph nodes. None of the patients had evidence of malignant or lymphomatous disease and only 3 had skin ulceration on the foot. DSA detected nodes in 9 patients (39%). In 3 cases the nodes were highly vascularized. Ultrasonography detected lymph nodes in 16 patients (70%). In all but 2 nodes a high velocity arterial flow was recorded. It is concluded that DSA and particularly duplex-Doppler ultrasonography are sensitive methods to detect vascularized lymph nodes and that such nodes are found in many patients with no evidence of malignancy or infection. PMID- 2187511 TI - Accuracy of digital radiography using stimulable phosphor for diagnosis of pneumothorax. AB - To evaluate the efficacy of digitized radiography in diagnosing pneumothorax 78 patients were examined with both the conventional film-screen technique and digital radiography. Of these 78 examinations 40 were normal and in 38 a pneumothorax was found. Four observers with different experience reviewed the films. In an ROC analysis no significant differences were found between the two systems. Between the observers, however, there were slight differences, one of them showing significantly lower specificity. PMID- 2187512 TI - Dynamic imaging of pulmonary ventilation in children using digital subtraction radiography. AB - Digital subtraction radiography is a sensitive method for imaging changes in pulmonary aeration during the respiratory cycle. The findings of 75 consecutive dynamic pulmonary examinations performed on 49 pediatric patients using this technique were reviewed together with the findings at chest radiography and, in 18 cases, with bronchoscopy. Symmetric diaphragmatic movement and synchronous, homogeneous variation in the attenuation of lung parenchyma indicated normal conditions in 9 (18%) patients. The most common abnormal finding (36 patients) was an asynchronous variation in the attenuation of the lung parenchyma. A greatly diminished or absent variation in attenuation was diagnostic for a serious air passage obstruction in 7 children. Other abnormal findings were a lowered amplitude of diaphragmatic movement, asynchronous diaphragmatic movement and mediastinal shift. In 10 patients (20%) the dynamic study showed parenchymal abnormalities when chest radiography was normal. Bronchoscopy was performed in 4 of these 10 patients and showed abnormalities in each case. PMID- 2187513 TI - Magnetic resonance imaging of thoracic hydatid disease. Correlation with clinical findings, radiography, ultrasonography, CT and pathology. AB - Two patients with thoracic manifestations of hydatid disease (HD) are discussed; one patient had recurrent HD of the chest wall and the other, intrapulmonary HD after rupture and intrathoracic extension of an infradiaphragmatic cyst. At magnetic resonance (MR) imaging the manifestations of HD in the thorax are similar to previously reported MR findings in HD in the liver. The presence of a low signal intensity rim on T2 weighted images representing the cyst wall was confirmed. On T1 weighted images cysts with heterogeneous low and intermediate signal intensity contents and a relatively high signal intensity wall were seen. 'Folded parasitic membranes' previously not described on MR were noted. Daughter cysts may have a low or high signal intensity depending on contents. Reactive changes in the lung may be quite marked compared with the liver, due to reaction to the parasite or simply because the lung is more easily compressed leading to secondary atelectasis. PMID- 2187514 TI - Fine-needle aspiration biopsy of liver hemangioma. AB - The results of 36 consecutive fine-needle aspiration biopsies of liver hemangiomas at two University Hospitals from the years 1981-1988 are described. The sizes of the lesions were 1 to 15 cm. Six patients had malignant disease, and liver metastasis was considered possible. In 2 cases the chief complaint was related to liver enlargement, and 28 patients had other abdominal symptoms. The aspiration was performed to confirm a suggested hemangioma in 18 and because of inconclusive findings at imaging in 18 cases. The aspirations were performed with sonographic guidance using 0.7 to 0.8 mm outer diameter needles. Cellular material from a hemangioma was obtained in 21 cases; only blood was aspirated in 5 cases. Hepatocytes were seen among abundant blood cells in 10, and some fibroblasts in 5 cases. One patient had significant bleeding that was treated with a transfusion of two units of blood. Nine patients were treated surgically, and histologic samples confirmed the diagnosis of hemangioma. None of the 27 non operated patients showed progression of the liver lesion at 3 to 48 months follow up. Fine-needle aspiration biopsy is helpful in the diagnosis of liver hemangioma. Confusion with malignancy is unlikely. Further experience will show the frequency of complications. PMID- 2187515 TI - Renal effects of the non-ionic contrast medium iopentol after intravenous injection in healthy volunteers. AB - Renal effects of the new non-ionic contrast medium iopentol in increasing doses were assessed and compared with the effects of physiologic saline. Twenty-four healthy male volunteers, allocated to three dose groups, were given iopentol intravenously in doses of 0.3, 0.6, and 1.2 g I/kg body weight, respectively. The highest dose group was also given physiologic saline separately as a control. The diuresis increased in all groups, most in the highest dose group, and with a concomitant fall of urine osmolality and increase in osmolar clearance. A slight decrease of serum osmolality, creatinine and urea occurred at 3 hours due to hemodilution. The glomerular filtration rate was unaffected by iopentol. The urinary excretion of albumin and beta 2-microglobulin was unchanged. However, urinary N-acetyl-beta-glucosaminidase and alkaline phosphatase increased significantly, most in the highest dose group. All changes were reversible. PMID- 2187516 TI - Implantation of the distal aorta: a technique for preservation of pelvic blood flow in aortofemoral reconstruction. AB - We report our initial experience with a previously undescribed variation of aortofemoral bypass. This technique is an alternative to end-to-side aortic anastomosis for preservation of pelvic blood flow. It involves an end-to-end proximal aortic anastomosis with implantation of the distal aorta into the posterior wall of the bifurcation graft. This approach has been used selectively for nine patients. Seven patients operated on using this technique had bilateral external iliac artery disease preventing retrograde perfusion of the pelvis. We used this procedure in two other young patients to preserve large inferior mesenteric and distal aortic lumbar vessels proximal to common iliac artery occlusions. Mean follow-up has been 20 months. There have been no deaths and no major complications. This technique provides the hemodynamic benefit of a proximal end-to-end aortic anastomosis while maintaining patency of the distal aorta and its branches. Additional technical advantages may include better suture line protection from the duodenum and a decreased potential for graft limb kinking. These factors may ultimately result in superior long-term graft patency. PMID- 2187517 TI - Preoperative evaluation of cardiac risk using dobutamine-thallium imaging in vascular surgery. AB - Coronary artery disease is frequently present in patients undergoing evaluation for reconstructive peripheral vascular surgery. Dobutamine-thallium imaging has been shown to be a reliable and sensitive noninvasive method for the detection of significant coronary artery disease. Eighty-seven candidates for vascular reconstruction underwent dobutamine-thallium imaging. Forty-eight patients had an abnormal dobutamine-thallium scan. Twenty-two patients had infarct only, while 26 had reversible ischemia demonstrated on dobutamine-thallium imaging. Fourteen of 26 patients with reversible ischemia underwent cardiac catheterization and 11 showed significant coronary artery disease. Seven patients underwent preoperative coronary bypass grafting or angioplasty. There were no postoperative myocardial events in this group. Three patients were denied surgery on the basis of unreconstructible coronary artery disease, and one patient refused further intervention. Ten patients with reversible myocardial ischemia on dobutamine thallium imaging underwent vascular surgical reconstruction without coronary revascularization and suffered a 40% incidence of postoperative myocardial ischemic events. Five patients were denied surgery because of presumed significant coronary artery disease on the basis of the dobutamine-thallium imaging and clinical evaluation alone. Thirty-nine patients with normal dobutamine-thallium scans underwent vascular reconstructive surgery with a 5% incidence of postoperative myocardial ischemia. Dobutamine-thallium imaging is a sensitive and reliable screening method which identifies those patients with coronary artery disease who are at high risk for perioperative myocardial ischemia following peripheral vascular surgery. PMID- 2187518 TI - Early patency of in situ saphenous vein bypasses as determined by intraoperative velocity waveform analysis. AB - Intraoperative velocity waveform analysis following in situ saphenous vein bypass grafting can identify abnormal hemodynamic conditions that correlate with the presence of a technical error or likelihood of perioperative thrombosis. Pulsed Doppler spectral analysis was used at operation to measure peak systolic blood flow velocity in the distal graft segment of 83 in situ saphenous vein bypasses to the popliteal (n = 35) or tibial (n = 48) arteries. Blood flow velocities were measured in the smallest diameter graft segment below the knee. Peak systolic blood flow velocity was greater than 40 cm/sec in 77 (93%) of grafts, and no early graft failures occurred. Low blood flow velocity (peak systolic blood flow velocity less than 40 cm/sec) was measured in six bypasses (7%) and was attributed to large (greater than 5 mm) vein diameter, residual hemodynamically significant lesions (intact valve leaflet, proximal arteriovenous fistula), or sclerosed vein segments. With the correction of these abnormalities, the 30 day patency for the entire series was 100%. The measurement of low blood flow velocity in the distal segment of an in situ saphenous vein bypass is an uncommon occurrence and mandates a thorough evaluation of the arterial reconstruction for correctable lesions. PMID- 2187519 TI - Can duplex scanning replace arteriography for lower extremity arterial disease? AB - This preliminary study was undertaken to determine if surgeons would choose different intervention for lower extremity occlusive disease when given basic clinical information and data from either a duplex scan or arteriogram. Information on degree of stenosis from duplex scans and arteriograms of 29 patients was indicated on an anatomical line drawing along with the ankle blood pressures and a brief clinical description. Based on these data sheets, six vascular surgeons chose a clinical plan in a blinded fashion for each patient. Each plan was placed into one of eight possible categories for comparison using the kappa statistic. Intraobserver agreement between surgeons' decisions based on duplex scanning versus those based on arteriography was very good (mean kappa .70 with exact agreement in 76%). Interobserver agreement between different surgeons' decisions based on the same studies was significantly less (mean kappa 0.56, p less than .05). Significant disparity in clinical approach occurred in 43% of the patients with nearly identical duplex scan and arteriogram reports, suggesting that much of the discrepancy lies in the clinical decision-making process. Clinical decisions made using duplex scans are very similar to those made using arteriograms. This technique can limit the need for arteriography in assessing patients with lower extremity arterial occlusion disease. PMID- 2187520 TI - Intraluminal vascular ultrasound: preliminary report of dimensional and morphologic accuracy. AB - The role of intraluminal ultrasound for diagnosis and monitoring treatment of vascular disease has yet to be defined. This study evaluated the dimensional precision and morphologic accuracy of an intraluminal ultrasound system which consists of a 5.5 French external diameter ultrasonic catheter with a central lumen for passage of a guidewire. Ultrasound images from five in-vitro human and three porcine arterial segments and two in-vivo arteriosclerotic canine arteries were compared to dimensions obtained from arteriograms and from sections of the specimens. Each gross and histological specimen and ultrasound image was scaled, photographed and enlarged up to 20 times and measured for vessel intraluminal and adventitial or outer diameter and wall thickness. Intraluminal and outer diameters and wall thickness from normal in-vitro specimens correlated significantly with dimensions obtained from histologic specimens (r = 0.99, p less than 0.005 for internal and outer diameters and r = 0.73, p less than 0.005 for wall thickness). The mean differences of luminal diameters measured from the vessels supported within a silicone rubber mold was 0.05 +/- 0.09 mm (n = 20). Diameters of outer diameter and wall thickness were less reliably defined, the average margin of error being 0.49 +/- 0.39 mm and 0.29 +/- 0.26 mm, respectively. The mean difference between in-vivo ultrasound and arteriographic diameters was 0.61 +/- 0.38 mm (n = 12). Correlation of luminal diameters between ultrasound and arteriogram was significant (r = 0.76, p less than 0.02). The ultrasound images also differentiated a laminated appearance of normal vessel anatomy from non-uniform or dense signals seen in atherosclerotic lesions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2187521 TI - Hysteroscopy for the investigation of abnormal uterine bleeding. PMID- 2187522 TI - Uterine fibroids: a clinical review. PMID- 2187523 TI - Novel screening strategies for early ovarian cancer by transabdominal ultrasonography. AB - Data collected during a prospective study to assess the efficacy of detecting early ovarian cancer by transabdominal ultrasonography have been used to refine and extend the screening procedure. The analysis was based on results from 5479 self-referred asymptomatic women, who were scheduled to undergo three annual screens consisting of one or more ultrasound scans. A positive result (based mainly on the presence of abnormal morphology) was obtained at 338 screens (326 women). Five patients with primary ovarian cancer (four stage 1a, one stage 1b; two at screen 1, three at screen 2) were identified (prevalence 0.09%). The apparent detection rate was 100% and the false-positive rate (FPR) was 3.5% at screen 1 and 2.3% overall. The use of abnormal morphology, or the maximum ovarian volume (MOV) greater than 96th centile as alternative criteria for a positive screen result, together with a defined volume change at rescan (VC) would give a FPR of 3.1% at screen 1 and 2.0% overall. The use of abnormal morphology alone at scan 1 and VC at rescan would give an overall FPR of 1.6%. The odds that a positive screen result would indicate the presence of an ovarian mass, a benign tumour, any ovarian cancer or primary ovarian cancer would be about 4 to 1, 2 to 1, 1 to 26, and 1 to 50 respectively. The results provide a more rational basis for the application and development of screening procedures for early ovarian cancer in both pre- and post-menopausal women. PMID- 2187524 TI - Is amniotic fluid quantitation of value in the diagnosis and conservative management of prelabour membrane rupture at term? AB - This study examined the hypothesis that ultrasound quantitation of amniotic fluid depth is of value in the diagnosis and management of prelabour rupture of the membranes (PROM) at term. The deepest vertical pool was measured in 151 consecutive patients with a history of suspected PROM for at least 10 h before labour. In 100 patients the diagnosis of PROM was confirmed by the collection of amniotic fluid at the vulva. There was no difference in mean depth of amniotic fluid in 100 patients with confirmed PROM, compared with 51 in whom PROM was not confirmed (48.5 mm SD 16.4 vs. 60.1 mm SD 16.5); the frequency of oligohydramnios (fluid depth less than 30 mm) was 5% and 5.8% respectively. There was no relation between ultrasound amniotic fluid quantitation and the onset of labour, the duration of labour nor the frequency of oxytocin augmentation in labour. The results show that ultrasound quantitation of amniotic fluid is of no value in the diagnosis and conservative management of PROM at term. PMID- 2187526 TI - Is routine antinatal booking vaginal examination necessary for reasons other than cervical cytology if ultrasound examination is planned? PMID- 2187525 TI - Intravenous treosulfan versus intravenous treosulfan plus cisplatinum in advanced ovarian carcinoma. AB - In a prospective, multicentre, randomized trial, the efficacy and tolerance of treosulfan alone was compared with that of treosulfan plus cisplatinum in 135 women with advanced ovarian carcinoma. No statistically significant difference was found between the two treatments in terms of median survival. Combined treatment was associated with significantly greater side-effects and haematological toxicity. Optimal survival with minimal toxicity can be achieved by using treosulfan alone in patients (mainly stages Ic or II) with minimal postoperative residual disease. Patients (likely to be stage III or IV) with greater residual disease should receive treosulfan plus cisplatinum. PMID- 2187527 TI - Interaction of Escherichia coli DNA polymerase I with azidoDNA and fluorescent DNA probes: identification of protein-DNA contacts. AB - The synthesis of an azidoDNA duplex and its use to photolabel DNA polymerases have been previously described (Gibson & Benkovic, 1987). We now present detailed experiments utilizing this azidoDNA photoprobe as a substrate for Escherichia coli DNA polymerase I (Klenow fragment) and the photoaffinity labeling of the protein. The azidoDNA duplex is an efficient substrate for both the polymerase and 3'----5' exonuclease activities of the enzyme. However, the hydrolytic degradation of the azido-bearing base is dramatically impaired. On the basis of the ability of these duplexes to photolabel the enzyme, we have determined that the protein contacts between five and seven bases of duplex DNA. Incubation of azidoDNA with the Klenow fragment in the presence of magnesium results in the in situ formation of a template-primer with the azido-bearing base bound at the polymerase catalytic site of the enzyme. Photolysis of this complex followed by proteolytic digestion and isolation of DNA-labeled peptides results in the identification of a single residue modified by the photoreactive DNA substrate. We identify Tyr766 as the modified amino acid and thus localize the catalytic site for polymerization in the protein. A mansyl-labeled DNA duplex has been prepared as a fluorescent probe of protein structure. This has been utilized to determine the location of the primer terminus when bound to the Klenow fragment. When the duplex contains five unpaired bases in the primer strand of the duplex, the primer terminus resides predominantly at the exonuclease catalytic site of the enzyme. Removal of the mismatched bases by the exonuclease activity of the enzyme yields a binary complex with the primer terminus now bound predominantly at the polymerase active site. Data are presented which suggest that the rate limiting step in the exonuclease activity of the enzyme is translocation of the primer terminus from polymerase to exonuclease catalytic sites. PMID- 2187528 TI - Yeast allosteric chorismate mutase is locked in the activated state by a single amino acid substitution. AB - Chorismate mutase, a branch-point enzyme in the aromatic amino acid pathway of Saccharomyces cerevisiae, and also a mutant chorismate mutase with a single amino acid substitution in the C-terminal part of the protein have been purified approximately 20-fold and 64-fold from overproducing strains, respectively. The wild-type enzyme is activated by tryptophan and subject to feedback inhibition by tyrosine, whereas the mutant enzyme does not respond to activation by tryptophan nor inhibition by tyrosine. Both enzymes are dimers consisting of two identical subunits of Mr 30,000, each one capable of binding one substrate and one activator molecule. Each subunit of the wild-type enzyme also binds one inhibitor molecule, whereas the mutant enzyme lost this ability. The enzyme reaction was observed by 1H NMR and shows a direct and irreversible conversion of chorismate to prephenate without the accumulation of any enzyme-free intermediates. The kinetic data of the wild-type chorismate mutase show positive cooperativity toward the substrate with a Hill coefficient of 1.71 and a [S]0.5 value of 4.0 mM. In the presence of the activator tryptophan, the cooperativity is lost. The enzyme has an [S]0.5 value of 1.2 mM in the presence of 10 microM tryptophan and an increased [S]0.5 value of 8.6 mM in the presence of 300 microM tyrosine. In the mutant enzyme, a loss of cooperativity was observed, and [S]0.5 was reduced to 1.0 mM. This enzyme is therefore locked in the activated state by a single amino acid substitution. PMID- 2187529 TI - Characterization of Escherichia coli thioredoxins with altered active site residues. AB - Escherichia coli thioredoxin is a small disulfide-containing redox protein with the active site sequence Cys-Gly-Pro-Cys-Lys. Mutations were made in this region of the thioredoxin gene and the mutant proteins expressed in E. coli strains lacking thioredoxin. Mutant proteins with a 17-membered or 11-membered disulfide ring were inactive in vivo. However, purified thioredoxin with the active site sequence Cys-Gly-Arg-Pro-Cys-Lys is still able to serve as a substrate for thioredoxin reductase and a reducing agent in the ribonucleotide reductase reaction, although with greatly reduced catalytic efficiency. A smaller disulfide ring, with the active site sequence Cys-Ala-Cys, does not turn over at a sufficient rate to be an effective reducing agent. Strain in the small ring favors the formation of intermolecular disulfide bonds. Alteration of the invariant proline to a serine has little effect on redox activity. The function of this residue may be in maintaining the stability of the active site region rather than participation in redox activity or protein-protein interactions. Mutation of the positively charged lysine in the active site to a glutamate residue raises the Km values with interacting enzymes. Although it has been proposed that the positive residue at position 36 is conserved to maintain the thiolate anion on Cys-32 (Kallis & Holmgren, 1985), the presence of the negative charge at this position does not alter the pH dependence of activity or fluorescence behavior. The lysine is most likely conserved to facilitate thioredoxin-protein interactions. PMID- 2187530 TI - Heterotropic effectors promote a global conformational change in aspartate transcarbamoylase. AB - The sigmoidal dependence of activity on substrate concentration exhibited by the regulatory enzyme aspartate transcarbamoylase (ATCase) of Escherichia coli is generally attributed to a ligand-promoted change in the quaternary structure of the enzyme. Although a global conformational change in ATCase upon the binding of ligands to some of the six active sites is well documented, a corresponding alteration in the structure of the wild-type enzyme upon the addition of the inhibitor, CTP, or the activator, ATP, has not been detected. Such evidence is essential for testing whether heterotropic, as well as homotropic, effects can be accounted for quantitatively in terms of coupled equilibria involving a conformational change in the enzyme and preferential binding of ligands to one conformation or the other. This evidence has now been obtained with a mutant form of ATCase in which Lys 143 in the regulatory chain was replaced by Ala, thereby perturbing interactions at the interface between the regulatory and catalytic chains in the enzyme and destabilizing the low-activity, compact (T) conformation relative to the high-activity, swollen (R) state. Difference sedimentation velocity experiments involving measurements of the changes caused by the binding of the bisubstrate analogue N-(phosphonacetyl)-L-aspartate demonstrated that the sedimentation coefficient of the mutant enzyme was intermediate between that observed for the T and R states of wild-type ATCase. We interpret the results as indicating that the [T]/[R] ratio in phosphate buffer at pH 7.0 is reduced from about 2 X 10(2) for the wild-type enzyme to 2.7 for r143Ala ATCase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2187531 TI - Guanine nucleotide binding characteristics of transducin: essential role of rhodopsin for rapid exchange of guanine nucleotides. AB - Transducin (Gt) is a member of a family of receptor-coupled signal-transducing guanine nucleotide (GN) binding proteins (G-proteins). Light-activated rhodopsin is known to catalyze GN exchange on Gt, resulting in the formation of the active state of the Gt alpha-GTP complex. However, purified preparations of Gt have been shown to exchange GN in the absence of activated receptors [Wessling-Resnick, M., & Johnson, G. L. (1987) Biochemistry 26, 4316-4323]. To evaluate the role of rhodopsin in the activation of Gt, we studied GN-binding characteristics of different preparations of Gt. Gt preparations obtained rom the supernate of GTP treated bovine rod outer segment (ROS) disks, followed by removal of free GTP on a Sephadex G-25 column, bound GTP gamma S at 30 degrees C in the absence of added exogenous rhodopsin with an activity of 1 mol of GTP gamma S bound/mol of Gt (Gt I preparations). Binding of GTP gamma S to Gt-I preparations closely correlated with the activation of ROS disk cGMP phosphodiesterase. GN-binding activity of Gt I preparations was dependent on reaction temperature, and no binding was observed at 4 degrees C. In the presence of 10 microM bleached rhodopsin, Gt-I preparations bound GTP gamma S at 4 degrees C. However, hexylagarose chromatography of Gt-I preparations led to a preparation of Gt that showed less than 0.1 mol/mol binding activity following 60-min incubation at 30 degrees C in the absence of rhodopsin (Gt-II preparations).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2187532 TI - Isolation and characterization of cloned cDNAs encoding human liver chlordecone reductase. AB - Chlordecone (Kepone), a toxic organochlorine pesticide, undergoes bioreduction to chlordecone alcohol in human liver. This reaction is controlled by a cytosolic enzyme, chlordecone reductase (CDR), which may be of the aldo-keto reductase family of xenobiotic metabolizing enzymes [Molowa et al. (1986) J. Biol. Chem. 261, 12624-12627]. To further investigate the primary structure and expression of CDR, we screened a library of human liver cDNAs cloned in the expression vector lambda gt11 and isolated an 800 bp cDNA that directed synthesis of a fusion protein recognized by polyclonal anti-CDR antibodies. Using this cDNA as a probe, we screened two human liver cDNA libraries and found several 1.2-kb cDNAs which would code for a polypeptide with 308 residues (35.8 kDa). However, a similar full-length cDNA, possibly the transcript of a pseudogene, contained an in-frame nonsense codon. The deduced protein sequence of CDR showed 65% similarity to the primary structure of human liver aldehyde reductase and 66% similarity to the inferred protein sequence of rat lens aldose reductase. A search of GenBank revealed significant nucleotide similarity to a cDNA coding for bovine lung prostaglandin f synthase and to a partial cDNA coding for frog lens rho crystallin. Southern blot analysis of human genomic DNA displayed between 45 and 65 kilobases of DNA hybridizable to CDR cDNA and demonstrated several restriction fragment length polymorphisms among 26 individuals. Northern blot analysis of RNA from human, gerbil, rabbit, hamster, mouse, and rat livers disclosed hybridization with CDR cDNA only for the first three species.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2187533 TI - Stark effect in wild-type and heterodimer-containing reaction centers from Rhodobacter capsulatus. AB - The effect of an external electric field on the optical absorption spectra of wild-type Rhodobacter capsulatus and two Rb. capsulatus reaction centers that have been genetically modified through site-directed mutagenesis (HisM200--- LeuM200 and HisM200----PheM200) was measured at 77 K. The two genetically modified reaction centers replace histidine M200, the axial ligand to the M-side bacteriochlorophyll of the special pair, with either leucine or phenylalanine. These substitutions result in the replacement of the M-side bacteriochlorophyll with bacteriopheophytin, forming a bacteriochlorophyll-bacteriopheophytin heterodimer. The magnitude of the change in dipole moment from the ground to excited state (delta mu app) and the angle delta between the Qy transition moment and the direction of delta mu app were measured for the special pair absorption band for all three reaction centers. The values for delta mu app and delta obtained for wild-type Rb. capsulatus (delta mu app = 6.7 +/- 1.0 D, delta = 38 +/- 3 degrees) were the same within experimental error as those of Rhodobacter sphaeroides and Rhodopseudomonas viridis. The values for delta mu app and delta obtained for the red-most Stark band of both heterodimers were the same, but delta mu was substantially different from that of wild-type reaction centers (HisM200----LeuM200, delta mu app greater than or equal to 14.1 D and delta = 33 +/- 3 degrees; HisM200----PheM200, delta mu app greater than or equal to 15.7 D and delta = 31 +/- 4 degrees).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2187534 TI - 5-[[(carboxymethyl)amino]methyl]uridine is found in the anticodon of yeast mitochondrial tRNAs recognizing two-codon families ending in a purine. AB - The modified nucleoside (U*) present in the wobble position of Saccharomyces cerevisiae mitochondrial tRNA(Leu) and tRNA(Trp) was isolated by thin-layer chromatography and HPLC. Its chromatographic, UV spectral, and mass spectrometric properties were shown to be identical with those of 5- [[(carboxymethyl)amino]methyl]uridine (cmnm5U). This nucleoside found in yeast mitochondrial tRNAs reading two-codon families ending in a purine permits the selective recognition of A and G in the third codon position. PMID- 2187535 TI - Spectropolarimetric analysis of the core histone octamer and its subunits. AB - The secondary structure of the calf thymus core histone octamer, (H2A-H2B-H3 H4)2, and its two physiological subunits, the H2A-H2B dimer and (H3-H4)2 tetramer, was analyzed by ORD spectropolarimetry as a function of temperature and solvent ionic strength within the ranges of these experimental parameters where assembly of the core histone octamer exhibits pronounced sensitivity. While the secondary structure of the dimer is relatively stable from 0.1 to 2.0 M NaCl, the secondary structure of the tetramer exhibits complex changes over this range of NaCl concentrations. Both complexes exhibit only modest responses to temperature changes. ORD spectra of very high and very low concentrations of stoichiometric mixtures of the core histones revealed no evidence of changes in the ordered structure of the histones as a result of the octamer assembly process at NaCl concentrations above 0.67 M, nor were time-dependent changes detected in the secondary structure of tetramer dissolved in low ionic strength solvent. The secondary structure of the chicken erythrocyte octamer dissolved in high concentrations of ammonium sulfate, including those of our crystallization conditions, was found to be essentially unchanged from that in 2 M NaCl when examined by both ORD and CD spectropolarimetry. The two well-defined cleaved products of the H2A-H2B dimer, cH2A-H2B and cH2A-cH2B, exhibited reduced amounts of ordered structure; in the case of the doubly cleaved moiety cH2A-cH2B, the reductions were so pronounced as to suggest marked structural rearrangements. PMID- 2187536 TI - The actions of melittin on membranes. AB - The molecular mechanisms underlying the various effects of melittin on membranes have not been completely defined and much of the evidence described indicates that different molecular mechanisms may underlie different actions of the peptide. Ideas about the formation of transbilayer aggregates of melittin under the influence of a transbilayer potential, and for bilayer structural perturbation arising from the location of the peptide helix within the head group region of the membrane have been made based on the crystal structure of the peptide, the kinetics and concentration dependence of melittins membrane actions, together with simple ideas about the conformational properties of amphipathic helical peptides and their interactions with membranes. Physical studies of the interaction of melittin with model membranes have been useful in determining the potential of the peptide to adopt different locations, orientations and association states within membranes under different conditions, but the relationship of the results obtained to the actions of melittin in cell membranes or under the influence of a membrane potential are unclear. Experimental definition of the interaction of melittin with more complex membranes, including the erythrocyte membrane or in bilayers under the influence of a transmembrane potential, will require direct study in these membranes. Experiments employing labeled melittins for ESR, NMR or fluorescence experiments are promising both for their sensitivity (ESR and fluorescence) and the ability to focus on the peptide within the background of endogenous proteins within cell membranes. The study of melittin in model membranes has been useful for the development of methodology for determination of membrane protein structures. Despite the structural complexity of integral membrane proteins, it is interesting that in some respects their study be more straightforward, lacking as they do the elusive properties of melittin (and other structurally labile membrane peptides) which limit the possibility of defining their interaction with membranes in terms of a single conformation, location, orientation and association state within the membrane. PMID- 2187537 TI - An update of the enzymology and regulation of sphingomyelin metabolism. AB - Sphingomyelin is found in plasma membranes and related organelles (such as endocytic vesicles and lysosomes) of all tissues, as well as in lipoproteins. Abnormalities in sphingomyelin metabolism have been associated with atherosclerosis, cancer and genetically transmitted diseases; however, except for Niemann-Pick disease, little is known about the mechanism for these disorders. Sphingomyelin biosynthesis de novo involves ceramide formation from serine and two mol of fatty acyl-CoA followed by addition of the phosphocholine headgroup. The headgroup appears to come from phosphatidylcholine, but other sources have not been ruled out. Factors that influence the rate of sphingomyelin synthesis include the availability of serine and palmitic acid, plus the relative activities of key enzymes of this pathway. Sphingomyelin turnover involves removal of the headgroup and amide-linked fatty acid by sphingomyelinases and ceramidases, respectively, which have been found in both lysosomes (with acidic pH optima) and plasma membranes (with neutral to alkaline pH optima). The enzymes of sphingomyelin turnover release ceramide and free sphingosine from endogenous substrates, which may have implications for the participation of a sphingomyelin/sphingosine cycle as another 'lipid second messenger' system. PMID- 2187538 TI - [Monoclonal antibodies to ceruloplasmin and their use for immunoenzyme assay of this protein]. AB - The hybridoma technology was used to produce monoclonal antibodies to human ceruloplasmin. The antibodies were found to be related to Ig G1. Using these monoclonal antibodies for PAP-ELISA of ceruloplasmin, it was possible to determine 10(-11) M of the protein. Monoclonal antibodies coupled to CNBr Sepharose were used for the rapid one-stage purification of ceruloplasmin from human placental serum. Ceruloplasmin obtained by this method contained no type 2 copper normally detected in protein preparations by conventional methods. PMID- 2187539 TI - Psychotropic drug development: challenge and promise. PMID- 2187540 TI - Short-term effects of the calcium channel blocker nimodipine (Bay-e-9736) in the management of primary degenerative dementia. AB - The etiology of Alzheimer's dementia (AD) is unknown, but several neurotransmitters, e.g., acetylcholine, have been implicated. Recently, the group of calcium channel antagonists have been reviewed for their potential neuropsychiatric applications. These agents are capable of enhancing cholinergic tone, neurofilament/microtubular stabilization, and regional perfusion rates. The following is a report of a randomized, double-blind, placebo-controlled, multicenter study of 227 AD patients treated with nimodipine, a 1.4 dihydropyridine derivative and calcium channel antagonist. The subgroup receiving active drug (30 mg t.i.d.) experienced a prophylactic benefit across eight measures over 12 treatment weeks when contrasted with the disease progression seen among placebo recipients. Calcium channel blockers as neurotransmitter modulators and/or via calcium's theoretical role in neurofibrillary tangles, proteolysis, or neurofilament formation may represent a therapeutic opportunity for the AD patient. PMID- 2187541 TI - Embryonic resistance to chemical and physical factors: manifestation, mechanism, role in reproduction and in adaptation to ecology. AB - Chemical and physical factors may adversely affect embryonic development. As an example of chemical factors, the effects of diabetic metabolic factors on embryonic development in mammals was reviewed. The existence of a stage-dependent reaction of embryos was found. At preimplantation stages diabetic metabolic factors are embryotoxic and lethal, and the blastocysts reacted by an "all-or none" response. Early somite embryos showed a higher resistance to the effects of diabetic metabolic factors resulting in various types of malformations. Both groups of embryos showed a very high sensitivity to the effects of combined diabetic metabolic factors. Congenital defects in term foetuses were lower than those observed during middle phases of pregnancy because some of the severely malformed embryos resorb during gestation. The effects of temperature on embryonic development were presented as an example of physical influences. In man, hyperthermia in pregnancy seems to correlate with defects in the development of the nervous and skeletal systems. In domestic animals, changes in environmental temperature correlated with depressions of reproduction rate. In laboratory animals, hyperthermia caused the development of congenital malformations. Stage-dependent as well as genetic differences in embryonic susceptibility to hyperthermia were found. Critical periods in sensitivity of embryos to hyperthermic influences were also observed. It has been shown that, in spite of similar external manifestations of the reaction of embryos to effects of diabetes and hyperthermia, the mechanism of these reactions was different. High resistance of early reptile and bird embryos to influences of temperature was considered as an example of morphofunctional adaptations in early embryogenesis of vertebrates to their development in terrestrial conditions. PMID- 2187542 TI - Endopeptidases and prohormone processing. AB - Peptide hormones and peptide transmitters are generated from polypeptide precursors by specific cleavage reactions which take place principally at sites formed by single or paired basic residues. Not all the possible cleavage sites are utilised, however, and the degree of processing of many propeptides has been found to vary according to the tissue of origin. The restricted nature of processing reactions could point to the existence of a series of enzymes with stringent specificities, recognising regions of structure in addition to the single or paired basic residues. Alternatively the action of processing enzymes may be directed by conformation of the pro-peptide which could focus the action of a protease onto or away from a particular site. In addition certain post translational modifications such as glycosylation or phosphorylation may influence the accessibility of a site to the approach of a processing enzyme. In this review we describe recent advances that have been made in the characteristization of proteolytic processing enzymes, we examine the relevance of the various factors that could account for restricted processing and discuss new approaches that may lead to better understanding of the mechanisms involved. PMID- 2187543 TI - Evidence for the involvement of vicinal sulfhydryl groups in the insulin stimulation of intracellular glucose metabolism in Zajdela hepatoma cells. AB - Phenylarsine oxide (PhAsO), a dithiol reagent that blocks insulin stimulation of glucose transport in 3T3 L1 cells, also altered insulin stimulation of intracellular glucose metabolism in Zajdela Hepatoma cultured cells. PhAsO (2 microM) similarly inhibited the insulin-induced glycogen and lipid syntheses without modifying the basal level of these processes, cell viability or the ATP content. Prior incubation of the cells with PhAsO did not prevent insulin binding to the cells, or activation of the receptor tyrosine kinase, while it minimally (16%) altered receptor internalization. These results indicate that cellular dithiols located at a post-receptor step are involved in the transduction of the insulin signal to intracellular glucose metabolism. PMID- 2187544 TI - Glycogenolytic effect of pancreastatin in the rat. AB - Pancreastatin is a novel 49-amino acid peptide with a C-terminal glycine amide. The peptide was isolated from porcine pancreatic extracts and shows a structural similarity to chromogranin A. The effect of synthetic porcine pancreastatin on blood glucose levels and hepatic glycogen content was investigated in rats in vivo. Pancreastatin (300 pmol/kg) produced a time-dependent decrease in glycogen content of liver and a slight hyperglycemia. Basal plasma insulin and glucagon levels were not modified by pancreastatin. We suggest that pancreastatin could play a biological role in the glucose metabolism through a glycogenolytic effect. PMID- 2187545 TI - [Contribution of echography to the diagnosis of cancer of the exocrine pancreas. Pitfalls and limits. Results of guided biopsy]. AB - The importance of ultrasound in the diagnosis of primary pancreatic adenocarcinoma is due to the wide use of ultrasound as a first diagnostic modality in the case of abdominal problems, immediately after the physical examination. The results of the ultrasound examination allow the physician to choose the best way to explore the pancreas further (CT, pancreatography, angiography, MRI). The technical quality of the ultrasound examination is mandatory and the radiologist must be able to recognize its insufficiencies. The pancreatic adenocarcinoma is difficult to see with ultrasound: infiltration, ill defined borders and echopattern; the lymph node or metastatic involvement is frequent and remains a good diagnostic sign. Many pitfalls can be attributed to this technique; the variations of the normal anatomy, the diversity and variable appearance of pancreatic lesions and the association with pancreatitis. The US guided puncture represents a way to limit the use of diagnostic exploratory laparotomy. PMID- 2187546 TI - [Combination radiotherapy and chemotherapy in cancer of the pancreas. Review of the literature and prospects]. AB - Overall prognosis of pancreatic adenocarcinoma is still very poor with median survival around 10 months after radical surgery in operable patients, or after full-dose radiation therapy in non-surgical candidates. In metastatic disease, multidrug chemotherapy regimens give a response rate of around 30% with median survival of 10 months. Random trials conducted by the GITSG in inoperable cases have shown improved results for chemoradiation with 5-FU for radiotherapy alone and a doubling of median survival with a 1-year survival of 40% vs 10%. Incorporation of Adriamycin in these combined modality protocols does not improve the results in terms of survival. Chemoradiation also shows improved results compared with chemotherapy alone. In patients amenable to radical surgery, adjuvant post-operative treatment with chemoradiation gave superior results over surgery alone with a doubling of median survival and a significant improvement of a two-year survival rate (42% versus 15%). Intra-operative radiation therapy leads to better local control but without a significant improvement in survival. With a better understanding of radio-chemotherapy interactions and mechanisms of radiosensitization through continuous infusion of fluorouracil and/or cisplatinum, these encouraging results should be confirmed within the next few years. PMID- 2187547 TI - [Use of monoclonal antibodies in the treatment of cancer of the pancreas: towards new progress?]. AB - Pancreatic cancers rank amongst the most deadly malignant diseases with a 5 year survival percentage less than 2% and few therapeutic approaches are hitherto available. This study presents the recent attempts to construct antibodies for therapy. The characterization of pancreatic tumor-associated antigens which might serve as target antigens for antibody therapy is the limiting factor before considering the treatment of pancreatic cancer with antibodies. Antigens such as CA 19-9, BW 494 and DU-PAN-2 have been reported to be associated with pancreatic cancers. However, monoclonal antibodies directed to these antigens was not proven to be specific enough to warrant therapeutic utilization and new tumor-associated antigens must be identified. Remarkable progress has been made recently in the construction of antibodies for therapy. Amongst these antibodies are "chimeric" antibodies, antibody heteroconjugates or hybrid antibodies. The in vivo utilization of those antibodies may well result in effective tumor-cell destruction. PMID- 2187548 TI - Continent cutaneous Ileostomy (Kock pouch) prior to renal transplantation. AB - Two patients in end-stage renal failure and with neurogenic bladders due to spina bifida complicated by myelomeningocele were considered for renal transplantation. One patient had had a right nephrectomy and urinary diversion via an ileal conduit; the other, after various external drainage procedures (cystostomy, bilateral nephrostomy), had had a tubular ileocystoplasty. Both underwent 2 surgical procedures prior to renal transplantation: in case 1 we performed a left nephrectomy and then ileal conduit removal + Kock pouch; in case 2 a bilateral nephrectomy was performed via 2 posterior incisions and then we removed the ileocystoplasty and formed the pouch. The continent ileostomy was formed according to the original technique with slight modifications. The patients have been followed up for 12 and 15 months after transplantation. PMID- 2187549 TI - Long-term results of colposuspension. AB - A series of 102 patients were treated by a technique of colposuspension similar to the Pereyra operation, in which a pair of monofilament sutures were tied over the rectus muscle; 79% of patients (78/99) reviewed 1 year after the operation were continent. During further follow-up (mean 4.5 years) there were 7 late failures, all within 4 years. Kaplan-Meier lifetable analysis showed 69% probability of continence at 5 years. The main factors associated with recurrent or persistent incontinence were detrusor instability (60% incontinent: 9/15) and previous failed colposuspension or multiple vaginal repairs (55% incontinent: 11/20). In the absence of these risk factors 90% of patients maintained continence throughout the follow-up period. This technique has given results at least equal to those reported for the Burch and Marshall-Marchetti-Krantz techniques of colposuspension. PMID- 2187550 TI - Experience with ultrasound guided transperineal prostatic needle biopsy 1985 1988. AB - A consecutive series of 143 ultrasound guided biopsies of the prostate have been analysed. In 84 patients, in whom carcinoma was suspected by both digital examination and ultrasound, 49 cancers were confirmed histologically. In 29 patients in whom digital examination suggested cancer but ultrasound was normal, 2 cancers were confirmed. In 20 patients with a normal digital examination but a suspicious ultrasound appearance, no cancers were proven. PMID- 2187551 TI - Silver alloy coated catheters reduce catheter-associated bacteriuria. AB - The tendency of indwelling catheters to cause urinary tract infection was evaluated in a randomised clinical study of 223 patients. A Foley catheter coated with silver alloy on both inner and outer surfaces was used in 60 patients; 60 others received a Teflonised latex Foley's catheter and the remaining 103 patients were excluded because of antibiotic treatment, diabetes, etc. There was a statistically significant difference in the incidence of catheter-associated bacteriuria (greater than 10(5) organisms/ml) in the 2 groups after 6 days' catheterisation: 6 patients with the silver coated catheter developed bacteriuria compared with 22 who had the Teflonised latex catheter. This suggests that the silver impregnated urethral catheters reduce the incidence of catheter-associated urinary tract infection. PMID- 2187552 TI - Comparative trial of sclerotherapy for hydroceles. AB - We present a prospective single-blind trial of sclerotherapy for hydroceles with tetradecyl sulphate and rolitetracycline as sclerosants. Twenty-seven hydroceles were treated with tetradecyl sulphate and 28 with rolitetracycline. The median follow-up was 13 months. There were no statistically significant differences between the 2 drugs in respect of cure rate and complications. The overall cure rate for both drugs was 96%. Complications were rare and common to both drugs. Tetradecyl sulphate and rolitetracycline were found to be equally effective as sclerosants. PMID- 2187553 TI - Fetal vesicoureteric reflux. AB - We present an analysis of 30 patients with fetal vesicoureteric reflux (VUR) from a series of 107 patients with prenatally diagnosed urinary tract anomalies. In 13 patients (Group 1) the fetal VUR was the only urinary tract abnormality. In 17 patients (Group 2) the fetal VUR was combined with other urinary tract problems. In 14 of 46 refluxing renal units there was no evidence of upper tract dilatation on a pre- and post-natal ultrasound examination. Any infant with postnatal urinary tract dilatation needs full urological investigations, including a micturating cystogram. A normal postnatal ultrasound examination does not exclude fetal VUR. PMID- 2187554 TI - Prenatally diagnosed reflux: a follow-up study. AB - This report analyses the characteristics and outcome of 25 infants with vesicoureteric reflux detected prenatally on the basis of dilatation of the fetal urinary tract. Sixteen infants had bilateral reflux--a total of 41 refluxing units. The high proportion of males (84%) contrasts with clinically presenting reflux, which is dominated by females. Prenatally diagnosed reflux is generally of a higher grade--usually grade IV. Eight children (32%) had coexistent congenital abnormalities. Chemoprophylaxis was completely effective in 17 children (68%), who remained infection-free; 3 children (12%) had a single urinary infection and were managed conservatively whilst 5 (20%) experienced 2 or more infections and required reimplantation or vesicostomy. Spontaneous cessation of reflux was observed in 6 (35%) of 17 refluxing ureters reassessed after a mean interval of 2.1 years. The significance of isotope findings was sometimes difficult to assess but results in 30 refluxing units support the concept that focal renal scarring is usually a consequence of infected reflux in postnatal life. PMID- 2187555 TI - Circumcision--which dressing? AB - Three methods of circumcision dressing were compared in a prospective trial. The results showed that dressings containing tincture of benzoin adversely affected wound healing in children. Dressing the wound with greasy tulle gave better results; the addition of soframycin did not produce better results than those achieved with ordinary paraffin tulle. PMID- 2187556 TI - Gallbladder cancer: the polyp-cancer sequence. PMID- 2187557 TI - Practicalities in the management of the acute abdomen. PMID- 2187558 TI - Asymptomatic gallstones. AB - The increasing detection of asymptomatic gallstones leads to difficult decisions for the surgeon and patient about whether the stones should be managed expectantly or surgically. This review examines the evidence currently available upon which such decisions must be based. Gallstones may present as biliary pain, acute cholecystitis, biliary obstruction or pancreatitis, but it is not clear who will develop symptoms and what are the commonest initial symptoms. Studies of the natural history of silent gallstones suggest that a large majority of patients with such stones will remain asymptomatic. However, diabetics are at increased risk, as are patients whose stones are detected initially at laparotomy. Incidental cholecystectomy is usually safe, and preoperative detection by ultrasonic screening is an advantage in planning the operation. Prophylactic cholecystectomy is not indicated to prevent gallbladder carcinoma (except in cases of porcelain gallbladder) and there is conflicting evidence about whether cholecystectomy predisposes to colorectal carcinoma. PMID- 2187559 TI - Graduated compression stockings in the prevention of postoperative deep vein thrombosis. AB - This review examines the role of graduated elastic compression stockings in the prevention of postoperative deep vein thrombosis. Used alone compression stockings reduce the incidence of postoperative deep vein thrombosis by approximately 60 per cent and when used in combination with other preventive methods, such as low dose heparin or intermittent calf compression, they further reduce the incidence by up to 85 per cent. PMID- 2187560 TI - Role of duplex scanning in the selection of patients for carotid endarterectomy. AB - A retrospective review of 63 patients undergoing duplex scanning and angiography for suspected carotid artery disease was performed to evaluate the need for routine angiography before carotid endarterectomy. A consultant surgeon (M.H.) made a simulated management decision on the basis of a clinical summary and a duplex scan report. Twenty-four patients were selected for surgery without angiography; duplex scanning had a sensitivity of 100 per cent and a specificity of 90 per cent in the detection of internal carotid artery stenosis. In two cases duplex scanning misdiagnosed a total occlusion as a critical stenosis. Eighteen patients failed to meet the criteria for surgery and were referred for angiography. Twenty-one patients were selected for conservative treatment on the basis of the duplex scan report. Combining the surgical and conservative groups (45 patients), duplex scanning had a sensitivity of 96 per cent and specificity of 95 per cent for the detection of stenosis greater than 50 per cent. In the identification of a total occlusion, duplex scanning had a poor sensitivity of 50 per cent. These results suggest that routine angiography before carotid endarterectomy is unnecessary in selected patients but that a suspected occlusion should be confirmed by angiography. PMID- 2187561 TI - Non-invasive estimation of peripheral resistance using Pulse Generated Runoff before femorodistal bypass. AB - The measurement of peripheral resistance (PR) is a useful technique for predicting the outcome of femorodistal bypass. In an attempt, noninvasively, to predict PR, Pulse Generated Runoff (PGR) was used to assess 35 consecutive patients undergoing femorodistal non-reversed vein bypass for critical ischaemia. The PGR subscores (anterior tibial, posterior tibial, peroneal, pedal arch status were correlated against the measured PR. Using multiple linear regression three resistance values were derived for runoff at different levels: (1) a single calf vessel (R1); (2) distal popliteal artery (R3); (3) irrespective of the level (R0). There was good agreement between the predicted resistances R0, R1 and R3 and the measured PR. In the single calf vessel group (R1) the limits of agreement (-0.41 to +0.39) and 95 per cent confidence interval (-0.16 to +0.14) with the measured PR were better than in the R0 and R3 groups. These levels of agreement are small enough to replace the measured PR with the predicted PR method. Using the appropriate resistance equation in a further prospective series of 14 cases, there was agreement between the predicted and measured PR (limits of agreement 0.67 to +0.41; 95 per cent confidence interval -0.26 to +0.15). These results confirm the value of PGR in the assessment of critically ischaemic limbs particularly with a single calf vessel. Calf vessel continuity with the pedal arch appears to be a major determinant of PR, particularly in the isolated calf vessel group. A non-invasive resistance value can be derived which will predict the intraoperative peripheral resistance and should help predict subsequent graft outcome. PMID- 2187562 TI - Intermittent hepatic dearterialization induces glucose intolerance: an experimental study in the rat. AB - Intermittent hepatic dearterialization is used in the palliative treatment of liver malignancy. However, its metabolic consequences are not established. Therefore the influences of the procedure on the plasma insulin, glucagon and glucose responses were studied in healthy rats and in rats with a tumour inoculated subcapsularly into the liver. To study the influence on stimulated islet hormone secretion we infused arginine intravenously (7 mg/min) for 30 min, because arginine is known to stimulate the secretion of both insulin and glucagon. During hepatic dearterialization, hyperglycaemia developed; mean(s.e.m.) blood glucose levels after 60 min of dearterialization were 20.2(1.3) mM versus 14.7(1.5)mM in controls (P less than 0.001). Concomitantly, compensatory hyperinsulinaemia and hypoglucagonaemia occurred. Furthermore, during both dearterialization and in the immediate reperfusion phase, the arginine-induced increase in plasma insulin levels was impaired (P less than 0.001), whereas the arginine-induced increase in plasma glucagon levels was not significantly affected. These changes were qualitatively the same in tumour-free and tumour-bearing rats. We conclude that glucose intolerance develops during selective hepatic dearterialization, which is evident both from basal hyperglycaemia and impaired insulin secretion. PMID- 2187563 TI - Whatever happened to Mary Ellen? AB - It is well recognized that the organized response to child abuse in the United States began with the rescue of a little girl named Mary Ellen from the abuse inflicted upon her by her stepmother. It is often forgotten, however, that Mary Ellen was, indeed, a real child who survived her horrendous start in life and went on to have a meaningful and productive life and raise children of her own. PMID- 2187564 TI - Moving child abuse and neglect prevention programs forward: improving program evaluations. AB - This paper focuses on evaluations of programs to prevent child abuse and neglect. It discusses the quality of the evaluations and offers suggestions for improvement to evaluators, program planners, and funders. Thirteen evaluations recommended by experts and published from 1978 through 1988 were reviewed. Using the true experiment as the standard of quality, we found evaluations frequently characterized by careful attention to methodologic detail. Evaluators describe eligibility criteria; half of the studies had control groups or followed progress. However, to learn more about prevention of abuse and neglect the caliber of evaluation research must improve. Evaluators do not define abuse or neglect; they accept reports of abuse. This has the effect of shifting the responsibility to others whose concerns and reporting standards differ. Lack of definition is reflected in a paucity of valid measurements; we could not assess the characteristics of families who benefit most from programs. Evaluators also omit important topics. Although seven evaluations studied health-related variables, no comprehensive analysis of the consequences and costs of medical neglect could be found; very little information on costs and benefits of any kind was available. PMID- 2187565 TI - Pathologic findings and pathogenesis of racetrack injuries. AB - Many lesions of the musculoskeletal system of racing horses are either acute traumatic lesions or are chronic biomechanically induced lesions that become suddenly unstable and provoke acute clinical signs. The latter lesions along with those of DJD are much more common and are of much greater overall economic importance to the racing industry than are the acute traumatic injuries. Chronic biomechanical lesions occur at predictable sites and are the result of an imbalance between repetitive microtrauma sustained in athletic performance and adaptive repair mechanisms of skeletal tissues. The distribution of these lesions in the limbs reflects the patterns of biomechanical forces placed on the skeleton during work at racing speeds and, therefore, reflects the type of racing activity for which the horse was bred. Lesions result when there is a failure of the stressed skeletal structures to adapt to the biomechanical forces placed upon them. Rest or a reduction in the level of training activity permit the healing of many asymptomatic and presumably some symptomatic lesions of the bony tissues. Articular cartilage, tendons, and ligaments have a lower capacity to resolve the damage and return to normal structure and function. PMID- 2187566 TI - Lameness diagnosis and treatment in the Standardbred racehorse. AB - Lameness of the Standardbred racehorse is a function of rigorous training programs, year-round racing schedules, hard racetrack surfaces, and the draft load. In this article, principles of lameness diagnosis and treatment are reviewed, with emphasis upon common or unique problems of the trotter and pacer. The role of physical therapy as an adjunct to medical and surgical treatment of lameness is described. Options for management of chronic pain are discussed, and a limited glossary of descriptive terms that are unique to harness racing is provided. PMID- 2187567 TI - Clinical experience with quantitative analysis of superficial digital flexor tendon injuries in Thoroughbred and Standardbred racehorses. AB - A method to quantitate as well as to document SDFT pathology has been described. This report indicates that computer-assisted evaluation of SDFT damage can improve the accuracy of prognosis in clinical practice. It would appear that a 3.8 severity rating is a limit past which prognosis for successful racing starts to worsen rapidly. PMID- 2187568 TI - Orthopedic surgery in the racehorse. AB - This article attempts to address what the authors consider to be the major orthopedic problems in the racehorse, with particular attention to their treatment and prognosis. These problems include fractures, osteochondral fragments, synovitis, degenerative joint disease, tendinitis, desmitis, osteochondritis dissecans, and subchondral cystic lesions of the joints. PMID- 2187569 TI - Respiratory problems in the racehorse. AB - Racetracks are ideal environments for the promotion of lower respiratory disease. The stabling is close and unclean, the population is nationally and internationally mobile, and the work the racehorse performs is traumatic to the respiratory tract. The running horse must complete a respiratory cycle with each stride. This relationship requires 130-150 breaths a minute in the running horse. Minute volume has been measured at 1300 L per minute and peak flow rates of 60 L/second in horses traveling at a modest 8 meters per second. As a comparison, the fastest running horse approaches 18 meters per second. The traumatic nature of racing to the respiratory tract is demonstrated by the fact that over 80% of the Thoroughbred racehorses show signs of exercise-induced pulmonary hemorrhage. Treating respiratory disease is a major part of racetrack practice. PMID- 2187570 TI - Surgery of the upper respiratory tract in the racehorse. AB - The authors discuss the surgical treatment of selected diseases of the upper airway of the racehorse. Although most of these conditions occur commonly and are easily diagnosed, their surgical management is often less straight-forward and may be surprisingly controversial. The authors' intent is to provide an overview of these problems and give some information regarding current treatment options. PMID- 2187571 TI - The use of sports medicine techniques in evaluating the problem equine athlete. AB - Discovering the cause of poor performance in racehorses can often represent a considerable challenge eluding the more common diagnostic techniques available at the racetrack. Application of sports medicine techniques to these problem cases can aid in the diagnosis of poor performance. Central to the development of this capability has been the use of highspeed treadmills, allowing the racehorse to be evaluated in the controlled laboratory setting, at exercise intensities equivalent to those of racing. Video and cinematographic gait analysis can be used in the diagnosis of subtle lameness conditions. Evaluating hoof balance at high speed has also become an important technique for both lameness diagnosis and prevention. Correcting hoof imbalance normalizes the applied stresses on joints, ligaments, and tendons. Abnormal upper airway function resulting in increased resistance to airflow is major cause of poor racing performance. Often this cause of upper airway dysfunction is difficult to evaluate at rest or after exercise. A definitive diagnosis can be made in these cases using treadmill endoscopy to visualize upper airway function during peak exercise. Lower airway function can also affect performance capability. Radiographic and scintigraphic imaging modalities can be used to evaluate both global and regional lung function in cases of suspected pneumonia, EIPH, COPD, or emphysema. Reduced metabolic fitness can be a primary cause of poor performance due to inherent differences in capability, pathologic changes in the major body systems involved in exercise, or inadequate training. Metabolic stress testing can be used to evaluate the level of fitness in these cases. Orthopedic imaging has also become a valuable diagnostic technique for evaluating musculoskeletal injuries. Scintigraphic evaluation of soft tissue and bone and CT scanning are used to localize the source of lameness and to grade the severity of various orthopedic conditions such as arthritis and stress-induced bone disease that are often difficult to categorize with conventional radiography. PMID- 2187572 TI - Radiology in racetrack practice. AB - This article focuses on the principles involved in making radiographs of equine limbs; understanding radiographic anatomy, including normal variations; and principles of radiographic interpretation. The influence of pathogenesis of disease on the radiographic image is considered. Diseases associated with racing as well as the developing racehorse are discussed. PMID- 2187573 TI - Lameness diagnosis and treatment in the Thoroughbred racehorse. AB - Thoroughbred racehorses are susceptible to any and all of the commonly described conditions that affect soundness in the horse. This discussion does not include every conceivable ailment or orthopedic condition that afflicts these animals. Rather, it confines itself to a few specific conditions of the racing Thoroughbred that are either unique to their particular endeavor or so overwhelmingly important to a successful racing career that they must, of necessity, be discussed. PMID- 2187574 TI - Lameness diagnosis and treatment in the quarter horse racehorse. AB - Lameness problems constitute a major part of racing Quarter Horse practice. This article considers the diagnosis, prognosis, and treatment of the frequently encountered lamenesses. The main conditions included are synovitis, intra articular fractures, osteochondritis dissecans, and degenerative joint disease as they relate to the coffin, fetlock, carpal, and tarsal joints. Intra-articular injection techniques and medications are discussed because of the frequency of joint disease. Bucked shins and stress fractures are also reviewed. PMID- 2187575 TI - Atypical hepatic vein leiomyoma extending into the right atrium: an unusual cause of the Budd-Chiari syndrome. AB - A 14-year-old male presented with a one week history of weakness, lightheadedness and vomiting. Bilateral pleural effusions were evident on chest radiography; electrocardiogram revealed decreased voltages. Echocardiogram, abdominal ultrasound and magnetic resonance imaging revealed a mass in an hepatic vein and the inferior vena cava extending up to and filling the right atrium. Under deep hypothermia and extracorporeal circulation the mass was removed en bloc. It originated from the hepatic vein. Pathology revealed a smooth muscle tumour intermediate between benign and malignant (atypical leiomyoma). This is the first reported pediatric primary leiomyoma of the hepatic vein. It caused the Budd Chiari syndrome, a rare pediatric entity. PMID- 2187576 TI - Usefulness of coronary artery angioplasty strategies in acute myocardial infarction. AB - The usefulness of percutaneous transluminal coronary angioplasty (PTCA) as an adjunct to thrombolytic therapy for acute myocardial infarction is the focus of intense clinical investigation. With an angiographically significant residual stenosis present in the infarct vessel in at least 70% of cases, PTCA has the potential to resolve residual ischemia of surviving myocardium; provide a route for nutrient influx to promote healing and reorganization by leukocytes and fibroblasts; and maintain ventricular wall integrity. Additionally, the residual lesion may interfere with flow to collateral vessels supplying other diseased vascular territories, or inhibit the delivery of inotropic or antiarrhythmic agents to a problematic peri-infarct region. Various angioplasty strategies have been devised to define the optimal timing of PTCA in several clinical settings. Although the impact on resting left ventricular performance has been disappointing except in cases of cardiogenic shock, an approach involving early angiography with thoughtful triage to PTCA when feasible, has been associated with improved survival at one- to three-year follow-up, compared with a 'thrombolysis only' approach. The results of clinical trials investigating the role of PTCA as a direct method of revascularization; as a 'rescue' procedure following failed thrombolysis; as an empiric, immediate or deferred strategy; or as an elective adjunct to thrombolytic therapy only in the presence of subsequent ischemia are reviewed in detail. PMID- 2187577 TI - Adaptation of small intestinal membrane transport processes during diabetes mellitus in rats. AB - Intestinal amino acid and glucose transport is increased in various disease states and physiological circumstances. This enhancement is generally due to an increase in transport capacity (Vmax) without a change in carrier affinity (KD). Furthermore, the increase in transport capacity is too large to be attributed, in most cases, to simple intestinal hypertrophy. In the streptozotocin-treated chronically diabetic rat model, specific binding indicated an enhanced total number of glucose carriers in the small intestine compared with controls. Furthermore, autoradiography reveals that specific phlorizin (i.e., glucose) binding extends into the intervillous region of the intestine, while in age matched controls binding is confined to the villous tip. These studies suggest that during experimental diabetes mellitus in rats, enhanced intestinal nutrient absorption may occur as a consequence of recruitment of carriers into previously nontransporting enterocytes. This review looks at ways in which this alteration may be influenced, and examines the expression of various isoforms of Na-K ATPase during streptozocin-induced diabetes mellitus. PMID- 2187578 TI - Intestinal microsomes: polyunsaturated fatty acid metabolism and regulation of enterocyte transport properties. AB - Recent evidence has suggested that transport of nutrients from the lumen to the interior of the gastrointestinal epithelium and exit of nutrients from the enterocyte to the circulation is governed by physicochemical properties of brush border and basolateral membranes, respectively. The main determinants of membrane properties are phospholipid, cholesterol, and fatty acyl chain composition (chain length and degree of unsaturation). Lipid synthesis occurs in enterocyte microsomes and the fine tuning of lipid composition is done at other subcellular sites by deacylation-reacylation or by changing the polar head group (e.g., by phosphatidylethanolamine methyltransferase). The present paper will focus on the mechanisms by which enterocyte membranes adapt functional properties in response to external stimuli. It is proposed that under the influence of internal or external stress, the enzymes of lipid metabolism in microsomes are modulated. These changes in lipid synthesis are reflected in other subcellular membranes, changing their physicochemical status and thus transport phenomena. One of the initial events appears to be alteration in desaturase enzyme activity. Our results suggest that desaturase activity and the fatty acyl profiles of the intestinal mucosal phospholipid rapidly respond to physiological conditions such as fasting and dietary fat treatment. PMID- 2187579 TI - Critical period programming of intestinal glucose transport via alterations in dietary fatty acid composition. AB - Intestinal adaptation occurs in response to physiological or pathological processes that include resection, aging, diabetes, radiation, lactation, chronic alcohol feeding, and feeding diets of varying lipid, protein, or carbohydrate composition. The mechanisms involved in the adaptive response include alterations in morphology, cell kinetics, digestive enzyme activity, transport, membrane lipid composition, and enzymes involved in lipid metabolism. This discussion will review the effect of aging and alterations in dietary fatty acid composition on the small intestine. In addition, it may be possible to program the intestinal response to aging by feeding diets of differing fatty acid composition during the critical period of weaning. Alterations in the ratio of polyunsaturated to saturated fatty acids in the diet modifies the age-associated changes in the intestinal uptake of glucose. The changes occur rapidly, progressively, and irreversibly, suggesting that the intestinal uptake of glucose is subject to critical period programming. The mechanism by which diet may modify the ability of the intestine to up- or down-regulate glucose transport requires further investigation. PMID- 2187580 TI - A growth-stimulating activity derived from the proximal small intestine is associated with an adaptive response. AB - Luminal nutrition is important for the maintenance of small intestinal structure and function. The equilibrium between crypt cell production and villous cell loss in the mucosal epithelium of the small intestine is altered under certain conditions such as after a small bowel resection. Immediately after resection, there is a marked increase in crypt cell proliferation giving rise to an adaptive hyperplasia in the remnant intestine and for this response luminal nutrition is a critical factor. We have previously demonstrated the presence of a growth stimulating (GS) activity in a heat-stable acidic extract of the rat proximal intestine 24, 48, and 96 h after resection, which is coincidental with an increase in crypt cell proliferation as measured by thymidine kinase activity. Eight days after resection when the GS activity is no longer detectable, the thymidine kinase activity returns to control values. The molecular weights of the peptides associated with this GS activity are 4500 and 1500, as determined by Sephadex gel filtration. Of note is that the oral intake of food is necessary for the appearance of the GS activity postoperatively. The presence of the GS activity has also been demonstrated upon refeeding after a fast, as well as at weaning in the rat, two physiological situations known to be associated with increased proliferation in the small intestine. This GS activity in the proximal intestine first detected in the resection model may represent a general mechanism by which food controls the cell renewal pattern of the small intestine. PMID- 2187581 TI - Comparison of different membranes for use in the colony-immunoblot technique. AB - We compared five different supports (Whatman paper filters Nos. 1, 5, and 40, nitrocellulose, and Nylon 66) for their suitability in the colony-immunoblot (CIB) technique. Results indicate that Whatman No. 5 filter paper recovered 94 98% of the bacterial colonies tested, were more resistant to tearing than the other Whatman papers tested, and showed reduced cross-reactions as compared with nitrocellulose membranes. Whatman No. 5 filters are 20 times less expensive than the nitrocellulose membranes usually used in the CIB technique. We thus adopted the former for our ecological studies of the murine oral cavity. PMID- 2187582 TI - Problems in the treatment of premenstrual syndrome. AB - Three categories of treatments for premenstrual syndrome (PMS) have been proposed: those designed to correct the cause of the disorder; those designed for symptom relief; and those aimed at eliminating the menstrual cycle. Many of these recommendations are based on poor research with loose definitions of the disorder and uncontrolled open trials. This paper reviews the literature on treatment methods with emphasis on recent random, placebo controlled, double-blind studies. The most effective current management of PMS is a conservative one including accurate diagnosis, stress control, sensible levels of diet and exercise and perhaps the use of alprazolam in the premenstrual period. Other approaches such as the use of mefenamic acid and evening oil of primrose remain unproven. Progesterone has been proven uneffective. Further research is required into the value of antidepressant medication. PMID- 2187583 TI - [Personality disorders in psychiatry]. AB - Psychiatric patients with personality disorders are among the most difficult because of the counter-transferential strain they put on clinicians and the paucity of specific treatment. The author develops the point that personality disorders are not diseases as implied in Axis I disorders, but social illness syndromes which depict systemic problems in which clinicians can be engulfed and entrapped. The difficult patient does not exist in isolation, a victim of his own drives and psyche, but rather is a specific socio-cultural actor living and emerging from a particular environmental context. Personality disorders are considered to be interpersonal patterns in which a person's debilitating behaviour elicits complementary behaviour that reinforces the original behaviour. Within a systems perspective, there is not a disordered personality so much as a disordering system of relationships. As with families and society, healers too become involved in the vicious cycle of personality disorders if they fail to see the manipulative interpersonal devices used by these patients. If clinicians accept too naively the lay person's simplistic belief that personality disorders are diseases to be treated by psychiatrists, they run the risk of fostering inappropriate passivity in patients in the face of life demands. Overindulgence and angry rejection are the two major pitfalls often seen in clinical practice. The approach proposed here may seem conterintuitive in laying stress on the need to actively resist the temptation to take over responsibility for a patient's life. There is a difference between a behaviour that a patient's illness (Axis I disorder) prevents him from controlling and an impulsive deliberate behaviour stemming from character pathology. It is a logical error to deal with personality disorders in the same manner and with the same conceptual terminology as for depressive and psychotic disorders. Principles of management are detailed and can be summarized as a kind firmness to bring back patients to take on their own responsibilities. PMID- 2187584 TI - Substance abuse and mental disorders: the dual diagnoses concept. AB - The concept of "dual diagnoses" is reviewed along with its clinical implications. Prevalence studies report substance abuse in psychiatric populations as ranging between 20% and 75%, depending on reporting, demographic variables and the community availability of substances. On the other hand, 20% to 65% of alcoholics entering rehabilitation suffer from another major psychiatric disorder. The clinical impact of dual diagnoses involves the development and expression of psychiatric disorders depending on the choice of drugs, the severity of psychopathology and risk of assaultive behaviour, possible misdiagnosis such as the confusion between alcoholism and affective disorders, the increased use of psychiatric resources including emergency, an earlier onset of symptomatology and poorer prognosis. The evolutionary impact of the concept, reflected in successive psychiatric diagnostic classifications, is discussed along with its bridging influence between the fields of mental health and addictionology. Appropriate assessment tools along with treatment strategies are suggested. Effective features of a group process include a nonconfrontational approach with emphasis on education, an expectation of abstinence as a goal, a discussion of diagnoses and medication and lastly particular attention to vocational rehabilitation and constructive use of leisure time. PMID- 2187585 TI - A controlled trial of cyproheptadine in cancer patients with anorexia and/or cachexia. AB - Anorexia, cachexia, and resultant weight loss are major clinical problems in a substantial proportion of patients with advanced cancer. Effective means of alleviating these problematic symptoms are lacking. Extensive clinical data demonstrate a weight enhancing effect for the serotonin antagonist, cyproheptadine, in several clinical situations. In addition, sound basic research suggests that cyproheptadine may be helpful in patients with cancer anorexia/cachexia. Because of this, the authors performed a randomized, placebo controlled, double-blinded clinical trial using cyproheptadine, 8 mg orally three times a day in 295 patients with advanced malignant disease. Patients assigned to cyproheptadine had less nausea (P = 0.02), less emesis (P = 0.11), more sedation (P = 0.07), and more dizziness (P = 0.01) than placebo patients. Patients' appetites, measured by serial patient-completed questionnaires, appeared to be mildly enhanced by cyproheptadine. Unfortunately, cyproheptadine did not significantly abate progressive weight loss in these patients with advanced malignant disease; patients assigned to cyproheptadine lost an average of 4.5 pounds per month compared to 4.9 pounds per month for patients assigned to a placebo (P = 0.72). PMID- 2187586 TI - High incidence of 17p13 chromosomal abnormalities in malignant histiocytosis. AB - Cytogenetic analyses of three patients during autopsy who had a pathologic diagnosis of malignant histiocytosis and of one patient who was strongly suspected to have malignant histiocytosis because of her clinical and hematologic findings were done. All three patients studied with bone marrow specimens showed polyploidy (3.4-20%). Two of three patients with chromosomal abnormalities showed 17p+ markers with a breakpoint at 17p13. Seven of 22 previously reported malignant histiocytosis patients (32%) with descriptions of detailed whole karyotypes have the 17p+ markers, including two of the authors' patients. Five of seven patients with 17p+ involved 17p13. Although breakpoints at the 17p+ in the remaining two were not described, their karyotypes were shown to possibly involve 17p13. The high incidence of this abnormality is not considered accidental, and this breakpoint is not usual in many other neoplastic disorders. These facts may indicate that 17p13 chromosome abnormality is a specific change of malignant histiocytosis. PMID- 2187587 TI - An immunohistochemical study of papillary tumors in the central nervous system. AB - An immunohistochemical study was performed on the paraffin sections of 25 tumors in the central nervous system (CNS) with prominent papillary configurations. These tumors included seven metastatic papillary carcinomas, six choroid plexus tumors, four papillary ependymomas, two myxopapillary ependymomas, two papillary pituitary adenomas, two astroblastomas, one papillary meningioma, and one anaplastic astrocytoma with significant papillary changes. The panel of antibodies applied included anti-glial fibrillary acidic protein (GFAP), anti carcinoembryonic antigen (CEA), anti-vimentin (VM), anti-S-100 protein (S-100 P), anti-cytokeratin, and anti-prealbumin antisera. All ependymomas and astroblastomas examined expressed both VM and GFAP, which were either absent or focally expressed in choroid plexus tumors. In contrast, all choroid plexus tumors showed anti-cytokeratin immunoreactivity that was absent in the ependymomas and astroblastomas. Five choroid plexus tumors also expressed S-100 P, thus differentiating them from metastatic carcinoma that showed negative immunostaining. Anti-CEA antisera immunoreactivity was seen in six metastatic tumors, whereas none of the primary CNS tumors expressed CEA. Prealbumin was expressed in four choroid plexus tumors and two metastatic tumors. Immunohistochemical typing using a panel of antibodies has allowed the differentiation of most of the papillary tumors in the CNS examined in this study. PMID- 2187588 TI - Analysis of prognostic factors in disseminated prostatic cancer. An update. Dutch Southeastern Urological Cooperative Group. AB - A statistical analysis of prognostic factors in 175 patients with hormonally treated disseminated prostatic cancer was done. The prognostic significance of performance status (PS), hemoglobin (Hb), alkaline phosphatase (Alk P), and testosterone was assessed with a univariate analysis. The authors did not find significant prognostic value in age, tumor size or grade, prostatic acid phosphatase, and prostate-specific antigen in these patients. In a multivariate logistic model (Cox regression), PS, Hb, and Alk P were found useful for dividing patients into prognostic groups. The prognosis for high-risk patients on standard hormonal treatment was very poor. The authors concluded that research on prognostic factors is useful and permits a division of patients into risk groups that makes choice of treatment more accurate. The use of new treatment combinations as a start treatment is appropriate for high-risk patients with disseminated prostatic cancer. PMID- 2187589 TI - Soft tissue sarcoma of the perineal region in childhood. A report from the Intergroup Rhabdomyosarcoma Studies I and II, 1972 through 1984. AB - Thirty-six previously untreated patients younger than 21 years of age with sarcoma arising in the perineal region were entered on the Intergroup Rhabdomyosarcoma Studies (IRS) I and II from 1972 through 1984. The tumor histologic subtype was alveolar rhabdomyosarcoma (RMS) in 20 patients (56%), embryonal RMS in 11 patients (30%), and other types of sarcoma in 5 patients (14%). Fifteen children had grossly complete surgical excision (Clinical Groups I and II), and 15 had localized gross residual tumor (Group III) after initial operative management. Six patients had distant metastases (Group IV) at diagnosis. Twelve patients without distant metastases underwent regional lymph node biopsy; tumor involvement was found in six. Subsequent treatment consisted of chemotherapy with vincristine (VCR) and dactinomycin (AMD) for all patients; patients in Groups III and IV also received cyclophosphamide (CYC) with or without Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH). Radiation therapy (RT) was administered to patients in Clinical Groups II, III, and IV. Overall, 28 (78%) patients achieved a complete clinical response. The 3 year disease-free survival rate for these patients was 42%, compared with 52% for all other patients in the combined IRS I and IRS II series (P = 0.44). The overall 3-year survival rate was 59%, compared with 64% for all other patients in IRS I and IRS II (P = 0.48). Aggressive treatment is needed in children with perineal sarcoma to improve their prognosis. PMID- 2187590 TI - The control of breast cancer. A World Health Organization perspective. AB - The greatest decrease in breast cancer mortality is likely to derive from applying globally existing therapies at an earlier stage. A high priority of the World Health Organization (WHO) cancer control program is the outreach approach that promotes worldwide access to cancer therapies of proven values. Therefore, the first priority in national health programs for breast cancer is to encourage patients to present for diagnosis and treatment at an earlier stage of the disease. In the development of guidelines for the early detection of breast cancer, the WHO emphasizes the importance of appropriate widespread coverage of high-risk groups as opposed to repetitive screening of low-risk groups, so that early detection will be effective. A WHO/USSR controlled trial of breast self examination and community-based adjuvant therapy is helping to develop the WHO global recommendations for the control of breast cancer. Depending on the extent of the breast cancer problem, the local resources, and the cultural situation, national health strategies should include all three main elements--public education, early detection, locally available treatment, or a combination of these to a national comprehensive program for the control of breast cancer. PMID- 2187591 TI - Transport of viral specimens. AB - The diagnosis of viral infections by culture relies on the collection of proper specimens, proper care to protect the virus in the specimens from environmental damage, and use of an adequate transport system to maintain virus activity. Collection of specimens with swabs that are toxic to either virus or cell culture should be avoided. A variety of transport media have been formulated, beginning with early bacteriological transport media. Certain swab-tube combinations have proven to be both effective and convenient. Of the liquid transport media, sucrose-based and broth-based media appear to be the most widely accepted and used. Studies on virus stability show that most viruses tested are sufficiently stable in transport media to withstand a transport time of 1 to 3 days. Some viruses may withstand longer transport times. In many cases, it is not necessary to store virus specimens in a refrigerator or send them to the laboratory on wet ice or frozen on dry ice. However, the specimen should not be exposed to environmental extremes. Modern viral transport media allow for more effective use of viral culture and culture enhancement techniques for the diagnosis of human viral infections. PMID- 2187592 TI - Immunoserology of infectious diseases. AB - The immune response to microorganisms not only participates in the elimination of unwanted organisms from the body, but also assists in diagnosis of infectious diseases. The nonspecific immune response is the first line of defense, assisting the body until the specific immune response can be mobilized to provide protective mechanisms. The specific immune response involves humoral or cell mediated immunity or both, dependent on the nature of the organism and its site of sequestration. A variety of test systems have been developed to identify the causative organisms of infectious diseases. Test systems used in immunoserology have classically included methods of detecting antigen-antibody reactions which range from complement fixation to immunoassay methods. Relevant test systems for detecting antigens and antibodies are described. With numerous test systems available to detect antigens and antibodies, there can be confusion regarding selection of the appropriate system for each application. Methods for detecting antibody to verify immunity differ from immunologic methods to diagnose disease. Techniques to detect soluble antigens present in active infectious states may appear similar to those used to detect antibody, but their differences should be appreciated. PMID- 2187593 TI - Vaccinia virus vectors: new strategies for producing recombinant vaccines. AB - The development and continued refinement of techniques for the efficient insertion and expression of heterologous DNA sequences from within the genomic context of infectious vaccinia virus recombinants are among the most promising current approaches towards effective immunoprophylaxis against a variety of protozoan, viral, and bacterial human pathogens. Because of its medical relevance, this area is the subject of intense research interest and has evolved rapidly during the past several years. This review (i) provides an updated overview of the technology that exists for assembling recombinant vaccinia virus strains, (ii) discusses the advantages and disadvantages of these approaches, (iii) outlines the areas of outgoing research directed towards overcoming the limitations of current techniques, and (iv) provides some insight (i.e., speculation) about probable future refinements in the use of vaccinia virus as a vector. PMID- 2187596 TI - Molecular cytogenetic analysis discloses complex genetic imbalance in a t(11;21) myelodysplastic syndrome. AB - Three cases of t(11;21)(q24;q11.2) myelodysplastic syndromes (MDS) showed karyotypic evolution resulting in the presence of two der(11)t(11;21) without normal chromosome 11 and with partial trisomy 21q. In one of these, we performed further molecular cytogenetic investigations which showed 1) that this rearrangement led to changes in the dosage and location of both c-ets 1 and c-ets 2 protooncogenes; and 2) that the presence of two 11q + chromosomes did not result from a nondisjunction, but that a second chromosome rearrangement had occurred. The final genetic imbalance resulting from this cytogenetic change involves at least hemizygosity for some sequences on the long arm of chromosome 11, including c-ets 1, plus trisomy for the most part of the long arm of chromosome 21, including c-ets 2. PMID- 2187595 TI - Bacterial spores and chemical sporicidal agents. AB - Bacterial spores are among the most resistant of all living cells to biocides, although the response depends on the stage of sporulation. The development of resistance to some agents such as chlorhexidine occurs much earlier in sporulation than does resistance to glutaraldehyde, which is a very late event. During germination or outgrowth or both, resistance is lost and the cells become as susceptible to biocides as nonsporulating bacteria. Mechanisms of spore resistance to, and the action of, biocides are discussed, and possible means of enhancing antispore activity are considered. The clinical and other uses of sporicidal and sporostatic chemical agents are described. PMID- 2187597 TI - Invasive and metastatic capacity of revertants of LFA-1-deficient mutant T-cell hybridomas. AB - From the highly metastatic TAM2D2 T-cell hybridoma we have previously generated three independent mutants that were deficient in the surface expression of the adhesion molecule Leukocyte Function-associated Antigen 1 (LFA-1). Both the invasive capacity and the metastatic potential of these mutants were greatly reduced compared with TAM2D2 cells (F.F. Roossien et al., J. Cell Biol., 108: 1979-1985, 1989). We now show that, during in vivo transplantation, LFA-1 is reinduced in these mutants. From such revertant cell populations obtained after two to three i.p. passages, we isolated clones with different LFA-1 levels. Of each of the three mutant cell lines, the clone with the highest and the one with the lowest LFA-1 level were selected for further study. Invasiveness in fibroblast monolayers correlated strongly with LFA-1 level; i.e., the low-LFA-1 clones (mean LFA level, approximately 10% of TAM2D2) invaded as poorly as the original mutants, whereas the high-LFA-1 clones (greater than 25% of TAM2D2) were highly invasive. Metastatic potential was determined after tail vein injection of 10(6) cells in syngeneic AKR mice. A difference was observed between high- and low-LFA-1 clones, albeit less striking than previously found between LFA-1 negative mutants and parental TAM2D2 cells. The high-LFA-1 clones developed metastases in more mice (76 versus 43%) and earlier (mean survival, 30 versus 37 days). These results provide further evidence for an important role of LFA-1 in invasion and metastasis of mouse T-cell hybridomas. PMID- 2187598 TI - Automated quantitation of immunocytochemically localized estrogen receptors in human breast cancer. AB - Frozen sections of breast tumor tissue have been stained using an immunoperoxidase [estrogen receptor (ER)-immunocytochemistry] kit incorporating a monoclonal antiserum [H222] to visualize nuclear human ERs. Quantitation of specific staining has been performed by manual procedures using optical microscopy and by a computer-assisted image analysis system (CAS 100). Initial investigations with a test panel of ER-immunocytochemistry-positive tumors revealed a good qualitative agreement between CAS and manual assessments. Reduced variance was, however, observed between quantified ER-immunocytochemistry results from four experienced investigators using the CAS analysis. An extended study confirmed the relationships between CAS and manual methods of assessment. These findings were evident when studies were scored either by assessment of the percentage of positively stained cells (n = 92; r = 0.919; P less than 0.01) or by H-score calculations (n = 92; r = 0.913; P less than 0.01). A good correlation was also found between CAS quantification and the results of an ER enzyme immunoassay of 48 primary breast cancer specimens (r = 0.715; P less than 0.05). In 49 cases it was possible to relate CAS-defined ER status and levels to the subsequent response of patients to endocrine therapy. ER was assessed on specimens obtained prior to commencement of treatments for recurrent breast cancer. Presuming the presence of ER to be a prerequisite for successful therapy, very good correlations between response and both status and levels of positivity were recorded. None of 16 patients with CAS-ER-negative tumors responded to treatment, while 16 of 33 (48.4%) CAS-ER-positive patients achieved an objective response according to International Union Against Cancer criteria. A relationship between response and the degree of CAS-ER positivity was obtained when the CAS score divisions of 0, 1-100, and greater than 100 (response rates, 0, 41, and 64%, respectively) were used. These data demonstrate that automated image analysis offers a reliable, reproducible procedure for quantifying ER in immunocytochemically stained sections. It has potential advantages over manual procedures, providing less opportunity for subjective influences in scoring sections. Future advances in software design should further reduce elements of subjectivity and increase both the speed and reliability of results. We anticipate image analysis becoming a valuable tool in investigations concerning, for example, the influence of heterogeneity of steroid receptor distribution on the rate of recurrence of breast cancer after mastectomy and in the clinical course of the disease. PMID- 2187599 TI - Activation of c-Ki-ras in human gastrointestinal dysplasias determined by direct sequencing of polymerase chain reaction products. AB - Activation of c-Ki-ras by point mutation within exon 1 was studied in 33 specimens of dysplastic gastrointestinal lesions or of cancers presumed to arise from dysplasia. Samples were obtained from patients with underlying ulcerative colitis or Barrett's esophagus, two diseases associated with dysplasia and increased rates of colonic or esophageal adenocarcinoma, respectively. Genomic DNA was amplified using primers bounding this exon in the polymerase chain reaction. Polymerase chain reaction products were analyzed by direct dideoxy sequencing. Three point mutations in codon 13 of c-Ki-ras were found, all in colonic specimens (two high-grade dysplasias and one adenocarcinoma arising in ulcerative colitis). No point mutations were observed in the second exon of c-Ki ras or in and around codons 12, 13, and 61 of c-N-ras and C-Ha-ras in a partial sampling of the specimens. These data indicate that ras family protooncogene activation is an uncommon event at this level of malignant progression in these disease states. Carcinogenesis in ulcerative colitis and Barrett's esophagus may proceed via different pathways than in sporadic colon cancer, perhaps involving loss or inactivation of suppressor genes. PMID- 2187594 TI - Pneumococcal resistance to antibiotics. AB - The geographic distribution of pneumococci resistant to one or more of the antibiotics penicillin, erythromycin, trimethoprim-sulfamethoxazole, and tetracycline appears to be expanding, and there exist foci of resistance to chloramphenicol and rifampin. Multiply resistant pneumococci are being encountered more commonly and are more often community acquired. Factors associated with infection caused by resistant pneumococci include young age, duration of hospitalization, infection with a pneumococcus of serogroup 6, 19, or 23 or serotype 14, and exposure to antibiotics to which the strain is resistant. At present, the most useful drugs for the management of resistant pneumococcal infections are cefotaxime, ceftriaxone, vancomycin, and rifampin. If the strains are susceptible, chloramphenicol may be useful as an alternative, less expensive agent. Appropriate interventions for the control of resistant pneumococcal outbreaks include investigation of the prevalence of resistant strains, isolation of patients, possible treatment of carriers, and reduction of usage of antibiotics to which the strain is resistant. The molecular mechanisms of penicillin resistance are related to the structure and function of penicillin binding proteins, and the mechanisms of resistance to other agents involved in multiple resistance are being elucidated. Recognition is increasing of the standard screening procedure for penicillin resistance, using a 1-microgram oxacillin disk. PMID- 2187600 TI - Beta 2-microglobulin expression in human embryonal neuroblastoma reflects its developmental regulation. AB - Class I major histocompatibility complex (MHC) antigen expression in neuroblastoma may play a role in the oncogenicity of this embryonal tumor of childhood. Since N-myc amplification in neuroblastoma tumors is associated with rapid tumor progression (33) and N-myc decreases Class I MHC antigen expression in rat neuroblastoma cells (21), we quantitated levels of N-myc mRNA and Class I MHC cell surface antigens in a panel of 24 human neuroblastoma cell lines. We found that N-myc expression is not invariably associated with low levels of beta 2-microglobulin (B2M) and Class I MHC antigen expression. As we considered that Class I MHC antigens may be regulated in association with the differentiation stage of the neuroblastoma tumor, we examined the expression of B2M during development of the human adrenal medulla, the tissue of origin of most neuroblastomas. We found that B2M is a marker of differentiated adrenal medullary cells, expressed late during the third trimester of development. Moreover, using morphological and immunological criteria, we found that B2M is expressed in differentiated tumor cells. These data suggest that the expression of B2M in neuroblastoma is associated with the stage of differentiation of the tumor cell and not N-myc expression. Furthermore, these findings suggest that neuroblastomas may correspond to the arrested differentiation of adrenal neuroblasts at different stages of development. PMID- 2187601 TI - Inhibition of p34cdc2 kinase activity by etoposide or irradiation as a mechanism of G2 arrest in Chinese hamster ovary cells. AB - The mammalian homologue of the yeast cdc2 gene product, p34cdc2, is a cell cycle regulated protein essential for mitosis. We have used polyclonal antisera raised against a peptide corresponding to the carboxyl terminus of the sequence of human cdc2 to study p34cdc2 in Chinese hamster ovary (CHO) cells. Major bands are immunoprecipitated at a molecular weight of 34,000, although not in the presence of competing antigenic peptide. p34cdc2 is coimmunoprecipitated with proteins of molecular weights of 52,000 and 57,000. Immunoprecipitates express histone H1 kinase activity which varies throughout the cell cycle, maximal activity being observed in G2-M. The activity of the p34cdc2 kinase varies according to its association with the Mr 52,000 and 57,000 proteins and according to their phosphorylation state. Treatment of either asynchronous CHO cells or an enriched G2 population with the antitumor agent, etoposide, results in rapid inhibition of immunoprecipitated p34cdc2 kinase activity, which is not due to a direct effect of drug upon the enzyme. p34cdc2 kinase activity recovers as cells arrest in G2 and a second etoposide treatment further inhibits p34cdc2 kinase activity and prolongs G2 arrest. Exposure of asynchronous CHO cells to gamma-irradiation also inhibits p34cdc2 kinase activity within 1 h. Again this activity recovers as cells accumulate in G2. These results suggest that DNA damage in CHO cells elicits a response which results in inhibition of p34cdc2 kinase activity and, consequently, G2 arrest. PMID- 2187602 TI - Possible role for p34cdc2 kinase in etoposide-induced cell death of Chinese hamster ovary cells. AB - In an effort to shed light upon the processes of antitumor drug-induced cell death, we have carried out a systemic study of the effects of the anti topoisomerase II agent, etoposide, on Chinese hamster ovary cells. Treatment of Chinese hamster ovary cells for 1 h with a 2-log cell-killing concentration of etoposide induces a high incidence of DNA single-strand breaks which are rapidly repaired upon drug removal. p34cdc2 kinase activity is inhibited within 1 h of addition of etoposide. Following removal of drug, cells accumulate transiently in G2. Upon recovery of p34cdc2 kinase activity (between 12 and 24 h posttreatment), approximately 50% of cells progress through mitosis which results in micronucleation. Examination of mitotic figures at various posttreatment incubation times indicates that micronucleation of daughter cells could be attributed to abnormal segregation of chromosomes during mitosis. Unexpectedly, p34cdc2 kinase activity remains elevated relative to untreated controls until 36 h post-etoposide treatment, a point where no further cell division takes place. This activity decreases by 48 h posttreatment, concomitant with a decrease in cell viability as estimated by the ability to exclude trypan blue. These results indicate that etoposide may induce cytotoxicity via gross chromosomal fragmentation, and that p34cdc2 kinase may be involved in this process. PMID- 2187603 TI - Comparison of two oral rehydration solutions in eutrophic infants with moderate acute diarrhea: results of an interim analysis. AB - A randomized, multicenter clinical trial comparing two oral rehydration solutions (ORS) with different sugar content and total osmolality was carried out in France. Solution A had 168 mmol/L of sugar and a total osmolarity of 326 mosm/kg; solution D had 90 mmol/L of sugar and a total osmolarity of 240 mosm/kg. Weight gain, stool output, and biologic variables were analyzed. This interim analysis included 49 infants (27 in group A and 22 in group D). Patients in both groups gained weight without any significant difference between the two ORS. Between admission and day 4, the overall number of stools and the number of liquid stools decreased. Laboratory values were within the normal range on admission and remained unchanged. The weight increase during the first 24 hours and the reduced frequency of stools was similar in both groups. PMID- 2187604 TI - Role of glucose polymer (cereal) in oral rehydration therapy. AB - The standard packaged glucose-based oral rehydration solution (ORS) provides optimal rehydration of acute diarrhea from any cause, but it does not reduce the volume, frequency, or duration of diarrhea. A new ORS formulation has been developed in which glucose is replaced by 50 to 60 gm of cereal flours, such as rice, wheat, maize, sorghum, or millet, or equivalent amounts of noncereal staples, such as boiled potato or plantain. In a clinical trial in children suffering from acute diarrhea, the staple-based or polymer-based ORS achieved a 40% to 60% reduction in the stool volume compared with the standard ORS. A three cell longitudinal study in rural Bangladesh involving 2,000 children aged 1 to 4 years demonstrated the superior efficacy of rice ORS compared with glucose ORS or no ORS. The cumulative recovery rate on day 3 was 66%, 24%, and 11% in the rice ORS, glucose ORS, and comparison groups, respectively. The study suggests that staple-based or food-based ORS is the optimal treatment of diarrhea. PMID- 2187605 TI - Postoperative rehydration. AB - Oral rehydration therapy (ORT) by the enteral route was compared with intravenous ORT in a group of patients undergoing cholecystectomy. Rehydration was successfully accomplished in both groups; however, enteral rehydration was more comfortable, more economical, and caused fewer complications than the intravenous infusion. When the study was expanded to patients undergoing colonic surgery, the results were encouraging; enteral ORT in patients undergoing gastric or duodenal surgery was less successful. PMID- 2187606 TI - Oral rehydration solutions in short bowel syndrome. AB - Patients with a reduced length of small intestine ending in a stoma experience loss of water and sodium, even when they take nothing by mouth. After food or drink, the loss from the stoma increases. Secretors are patients who lose more from the stoma than they take in by mouth. Absorbers are those whose output is less than their intake. In both groups, the sodium concentration of the effluent is about 90 mmol/L. The secretors are in constant negative sodium balance of up to 400 mmol/day and can only maintain balance with self-administered parenteral water and sodium. The absorbers may lose 200 mmol of sodium daily and need to take an oral sodium supplement to maintain balance. The optimal oral replacement solution has a concentration of at least 90 mmol/L of sodium. Lower sodium concentrations, or drinking water without sodium, lead to increased sodium losses and negative balance. The role of glucose, glucose polymers, or bicarbonate in promoting sodium absorption in the short bowel is unclear. Potassium losses from a small intestinal stoma are small. A modified glucose electrolyte solution, without potassium or bicarbonate and with a sodium concentration of 90 to 120 mmol/L, is appropriate for patients with an intestinal stomal output of 1 to 2 L daily. Once the output rises above 2 L daily, it is difficult to maintain sodium balance with an oral supplement. PMID- 2187607 TI - Scientific rationale for oral rehydration therapy. AB - A scientific rationale for the use of oral rehydration therapy (ORT) in treating severe diarrhea is presented. Because diarrhea impairs the absorptive and secretory functions of the gastrointestinal tract, volume and solute deficits must be corrected through ORT. The composition of the ideal ORT solution--one that maximizes absorption of water, electrolytes, and nutrients--is discussed in relation to the digestive-absorptive mechanisms of the gut. PMID- 2187608 TI - History of the development of oral rehydration therapy. AB - Humans have often used oral fluids to replace perceived losses of water, either instinctively or with a therapeutic orientation in the form of folk remedies. Replacement therapy with intravenous (IV) fluids was formally introduced in the last century for the treatment of patients with cholera. The modern implementation of oral replacement therapy was begun by pediatricians in the 1940s who used electrolyte solutions as maintenance therapy in mildly purging children with diarrhea. However, the scientific development of oral rehydration therapy (ORT) has occurred only in the last 30 years. Basic physiologic research in the 1950s demonstrated the cotransport mechanism of sodium and organic solutes (sugars and amino acids) in the intestinal cells, thereby establishing the scientific basis for ORT. The use of ORT based on scientific observations was first reported in 1964 from the Philippines by Phillips and coworkers. Research laboratories in Dhaka and Calcutta subsequently demonstrated that the mechanism of sodium and glucose cotransport remains intact in cholera patients and that oral solutions can successfully rehydrate and maintain hydration in these patients. Clinical studies carried out in Dhaka and Calcutta confirmed the efficacy of oral rehydration solutions (ORS) and showed that nearly 80% of IV fluid could be saved if patients were hydrated by the oral route. Further studies demonstrated the safety and efficacy of ORT in patients of all ages suffering from acute diarrhea of any cause. The use of ORT has substantially reduced morbidity and mortality from acute diarrhea, particularly after the World Health Organization adopted and promoted ORT on a worldwide scale. Researchers continue to search for better ORS formulations in terms of safety, efficacy, availability, and cost. Food-based ORS are a promising area of research. The use of a sound scientific method, the establishment of a close link between basic and clinical science, and the use of field studies have proved to be major assets in the development of ORT. PMID- 2187609 TI - The erratic evolution of cholera therapy: from folklore to science. AB - Cholera is an exceptionally frightening epidemic disease because it kills its victims so very rapidly. The development of cholera therapy is traced from the early 19th century purges and bloodletting to the current use of oral rehydration solutions. PMID- 2187610 TI - Worldwide impact of oral rehydration therapy. AB - Oral rehydration therapy (ORT) has had a dramatic global impact. The worldwide consequences of this therapy are discussed in four categories: (1) adoption of ORT as the primary therapy for acute dehydrating diarrhea; (2) establishment of national ORT programs; (3) scientific knowledge gained from studies into intestinal absorption of oral rehydration solutions; and (4) implications of ORT for the next decade. The Diarrheal Disease Control Program has been assigned a high priority by the World Health Organization. It now includes 99% of the population of the developing world, although it is not uniformly implemented. Because knowledge of how to use ORT parallels implementation, it is hoped that expanded training of community health workers will increase implementation. In addition, specific indications for ORT need further study and refinement so that community health workers may learn to distinguish between diarrheal episodes that require such therapy and those that do not. Better scientific understanding of intestinal absorption of ORT fluids has led to the development of new formulations that enhance absorption of nutrients and repletion of electrolytes. The optimal composition of such revised solutions has yet to be established. In addition to these improvements in utilization, distribution, education, and application of ORT, other measures to reduce the morbidity and mortality from diarrhea can be expected in the areas of better infant feeding practices, improved sanitation, management of persistent diarrhea, targeted therapy for particular groups of infants at high risk, and immunization. PMID- 2187611 TI - Current controversies in oral rehydration solution formulation. AB - Although the importance of oral rehydration therapy for acute diarrhea is unquestioned, controversy remains about the preparation and formulation of the oral rehydration solutions (ORS). There is disagreement about whether the ORS should be homemade or commercially prepared, what constitutes the optimal sodium content, what base (if any) should be present in the ORS, and whether other nutrients can be substituted entirely or in part for glucose. These issues are discussed and recommendations for the ideal ORS are presented. PMID- 2187612 TI - Studies of oral rehydration solutions in animal models. AB - Ideas about the optimal composition of oral rehydration solutions (ORS) continue to evolve. A controlled clinical trial is the only way to determine whether a new ORS is superior to an established solution, but attempts have been made to prescreen new ORS in a variety of animal models, most of which involve intestinal perfusion. Most of the work has been performed in the healthy small intestine of rats, either in short segments or in its entirety, or in the diseased small intestine that has been infected with rotavirus or exposed to cholera toxin to induce a secretory state. Despite the marked pathophysiologic differences between these models, the qualitative findings using new and established ORS have been remarkably similar. Overall, these animal models have emphasized the potential benefit of using a hypotonic ORS (osmolality, 240 mosm/kg or less). The optimal sodium concentration has been found to be 50 to 60 mmol/L, and the optimal glucose concentration 90 to 111 mmol/L. These models have also been satisfactorily used to examine the value of glucose polymer and food-based ORS. The findings suggest that for a given substrate load initial osmolality is probably the chief determinant of water absorption, which is substantially greater from the more hypotonic solutions. Results from animal experiments must be interpreted with caution because of their physiologic limitations. Nevertheless, they have provided insight into the physiology of oral rehydration therapy and may be useful in identifying ORS for evaluation by clinical trial. PMID- 2187613 TI - Studies in human models. AB - Advances in the development of oral rehydration solutions (ORS) for the treatment of diarrheal disease depend on a knowledge of the disease process itself and of the factors that determine the movement of water and solutes across the gut. The formulation of ORS in current use is based on information derived from a number of different experimental approaches that attempt to take account of these factors. The fate of orally ingested solutions depends first on the processes of gastric emptying that control the rate of entry of fluid to the small intestine and second on the rates of absorption and secretion in the intestine. In the absence of a model that can reliably assess the effects of these two processes together, they are normally investigated separately. The methods of choice for measurement of gastric emptying are gamma scintigraphy and gastric aspiration. Multi-lumen perfusion techniques permit measurement of net flux in short segments of intestine. A promising new technique that takes account of both gastric emptying and intestinal transport involves measurement of accumulation in the circulation of isotopic tracers for water added to ingested solutions. The efficacy of new solutions must, however, ultimately be assessed in clinical trials on patients. PMID- 2187614 TI - Clinical experience with a hypotonic oral rehydration solution for treatment of pediatric gastroenteritis in the United Kingdom. AB - Animal and human perfusion studies suggest that water absorption can be optimized by glucose-electrolyte solutions with low total osmolality. A new oral rehydration solution (ORS), reformulated Dioralyte (RD), containing 60 mmol/L of sodium and 90 mmol/L of glucose with an osmolality of 240 mosm/kg, was tested for safety and efficacy in children in the United Kingdom with acute gastroenteritis. In a double-blind, controlled trial, RD was compared with standard Dioralyte (SD), a widely used low-sodium, high-glucose solution containing 35 mmol/L of sodium and 200 mmol/L of glucose, with an osmolality of 310 mosm/kg. Infants and children aged 2 weeks to 3 years admitted with acute gastroenteritis of less than five days' duration and mild to moderate dehydration were randomized to receive either RD or SD. Clinical and laboratory assessments were made on admission and 12, 24, and 48 hours after treatment. Thirty-two children were enrolled in the study; 14 received RD and 18 SD. No adverse effects from either ORS were reported. Efficacy was evaluated in 24 patients, of whom eight received RD and 16 SD. Total ORS intake and intake in milliliters per kilogram were similar in both treatment groups. Mean fluid balance, mean percentage weight change, and median stool frequency did not differ between the groups at 12, 24, and 48 hours after onset of treatment. Three (12.5%) patients had greater than or equal to 0.05% reducing substances in the stool during treatment, and the incidence was similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2187615 TI - Effect of an antimicrobial-containing varnish on root demineralisation in situ. AB - The effect of an antimicrobial-containing varnish on root demineralisation was investigated. The in situ demineralisation effect on the varnish, with or without the active ingredients chlorhexidine and thymol, was measured by means of microradiography in comparison with no application after a 2-week period in vivo. Furthermore, the effect of one or two applications was investigated by the 10 participants who carried sound intact roots in an appliance for four consecutive 2-week periods. In each period, different roots were mounted in the buccal flanges of a lower prosthesis, the experiment being of a randomized cross-over design. The results show that: (1) A single varnish treatment with active ingredients reduced lesion depth and mineral loss by about 77 and 82%, respectively. (2) The control varnish had no effect, and it can be concluded that antimicrobial-releasing varnishes are promising materials for root caries prevention. PMID- 2187616 TI - Influence of fluoride on in vitro remineralization of artificial subsurface lesions determined with a sandwich technique. AB - Remineralization experiments of bovine enamel with subsurface lesions were carried out with the use of a sandwich technique. The remineralizing solutions contained no or 2 ppm fluoride added to the solution. The amount of remineralization was determined after remineralization periods up to 324 by means of quantitative microradiography. After 84 h the group with fluoride showed significantly (p less than 0.05) less remineralization than the nonfluoride group. This inhibition of fluoride on the remineralization may be explained by the inhibiting effect that fluoride at certain concentrations has on the crystal growth of apatites. PMID- 2187617 TI - [Transfer of resistance to the newer beta-lactam antibiotics in Czechoslovakia]. AB - Transmitted resistance to recent cephalosporin antibiotics of the third generation was first proved in 1983 by the authors. Approximately five years later the authors revealed during systematic monitoring of bacterial strains resistant to cephtazidime, cephtriaxone and cephotaxim also transmitted resistance to these and other more recent beta-lactam antibiotics in Czechoslovakia. The authors advocate rational use of new cephalosporins and other beta-lactams (e. g. aztreonam) as reserve antibiotics. PMID- 2187618 TI - [Nursing and health care in hospitals run by religious orders]. PMID- 2187619 TI - Calcium activated neutral protease--structure-function relationship and functional implications. PMID- 2187620 TI - Immunocytochemical evidence for centrosomal phosphoproteins in mitotic sea urchin eggs. AB - The change in distribution of centrosomal phosphoproteins was examined in sea urchin eggs from fertilization to the first cleavage by immunofluorescence staining with the anti-phosphoprotein antibodies, MPM-1 and MPM-2. The antibodies reacted with female pronuclei in unfertilized eggs as well as centriolar complexes located at the base of sperm flagella. After insemination, male and female pronuclei fused together to form a zygotic nucleus which was visualized by staining of fertilized eggs with the antiphosphoprotein antibodies. No major change in staining pattern was detected in extracted whole eggs until mitosis. As the fertilized eggs approached mitosis, however, the antigens started to redistribute from nuclei to the perinuclear position where the mitotic centrosomes were located. Detailed immunofluorescence observation of isolated spindles revealed that the phosphoantigens were retained in isolated structures. A major 225 kd polypeptide was recognized by the antibodies, suggesting that the 225 kd protein is a phosphocomponent of centrosomes. The area recognized by the antibody in mitotic poles enlarged with the progress of mitosis, suggesting that the antigens were apparently localized in the centrosphere. Centrospheres prepared from isolated spindles by salt extraction strongly reacted with the antibodies. One or two bright dots, which may represent centrioles, were visible in the isolated centrosphere. At the end of mitosis, the antigens again appeared in the newly formed daughter nuclei. Centriole-containing cytasters and centriole free monasters were parthenogenetically induced in unfertilized eggs (Kuriyama and Borisy, (1983) J. Cell Sci. 61: 175-189). The antibodies stained centers of both the asters whether they contained centrioles or not, indicating that the antibodies recognizes the components of the pericentriolar material. PMID- 2187621 TI - Isolation and short-term culture of mouse splenic erythroblastic islands. AB - We isolated and cultured erythroblastic islands (EI) from the spleens of phlebotomized mice using a combination of collagenase digestion, unit gravity sedimentation, and Percoll density gradients separation. The isolated EI were composed of surrounding erythroid cells and central stromal macrophages (M phi), which were identified by Forssman antigen. While 60% of the erythroblasts incorporated bromodeoxyuridine, the M phi did not. EI could be maintained on a plastic dish for a short period in the presence of erythropoietin. Two hours later, the central M phi spread well and bound to erythroblasts via cytoplasmic processes. One day later, erythropoietic activity on the M phi surface continued, although their processes had retracted. Some EI showed synchronized expansion of erythroblasts and others showed differentiation to reticulocytes. Two days later, about 50% of the EI still showed erythropoietic activity and most erythroblasts differentiated to the orthochromatic stage. On the other hand, the M phi secreted colony-stimulating activity during the culture. It was infrequently observed that erythroid and myeloid populations simultaneously expanded on a central M phi. These results indicate that this EI culture system is useful for studying interactions between the stomal M phi and hematopoietic cells. PMID- 2187622 TI - The undercoat of adherens junctions: a key specialized structure in organogenesis and carcinogenesis. PMID- 2187623 TI - Yeast ribosomal proteins: XI. Molecular analysis of two genes encoding YL41, an extremely small and basic ribosomal protein, from Saccharomyces cerevisiae. AB - Two genes encoding ribosomal protein YL41 were cloned from Saccharomyces cerevisiae chromosomal DNA. Both genes contain an uninterrupted region of only 75 nucleotides coding for a protein of 3.3 kD. Within the coding regions the nucleotide sequences are virtually identical, whereas in both the 5'- and 3' flanking regions the two genes differ significantly from each other. The deduced protein shows an arginine and lysine content of 68 percent, i.e., 17 out of 25 residues, and the basic residues are evenly distributed over the molecule. When compared to the ribosomal protein sequences currently available no counterpart to YL41 could be found in prokaryotes and it seems likely that YL41 is a eukaryote specific ribosomal protein. PMID- 2187624 TI - Application of the beta-glucuronidase gene fusion system to Saccharomyces cerevisiae. AB - Bacterial beta-glucuronidase (GUS) has been described as a useful reporter enzyme for gene fusion studies in bacteria and plants. Here we report the expression of GUS in yeast to illustrate further applications of this enzyme as a quantitative tool for measuring gene activity, as a colour selection marker and as a versatile system for protein targeting studies. There is no intrinsic GUS activity in any yeast strain tested. GUS was expressed in transgenic yeast on a multiple-copy vector under the control of the alcohol dehydrogenase 1 (ADH1) promoter. The enzyme is stable in yeast and its activity may be monitored by very sensitive colorimetric or fluorometric methods in extracts, or by the histochemical reagent 5-bromo-4-chloro-3-indolylglucuronide (X-Gluc) on plates. To test the efficacy of GUS as a reporter for targeting proteins into different subcellular compartments in vivo, we fused the presequence of the mitochondrial tryptophanyl-tRNA synthetase gene (MSW) to the amino terminus of GUS. The activity of the fusion protein is not substantially impaired and it is imported efficiently into yeast mitochondria. PMID- 2187625 TI - The effect of DNA replication on mutation of the Saccharomyces cerevisiae CDC8 gene. AB - Incubation in YPD medium under permissive conditions when DNA replication is going on, strongly stimulates the induction of cdc+ colonies of UV-irradiated cells of yeast strains HB23 (cdc8-1/cdc8-3), HB26 (cdc8-3/cdc8-3) and HB7 (cdc8 1/cdc8-1). Inhibition of DNA replication by hydroxyurea, araCMP, cycloheximide or caffeine or else by incubation in phosphate buffer pH 7.0, abolishes this stimulation. Thus the replication of DNA is strongly correlated with the high induction of cdc+ colonies by UV irradiation. It is postulated that these UV induced cdc+ colonies arise as the result infidelity in DNA replication. PMID- 2187627 TI - Phospholipid-based reverse micelles. AB - Physicochemical investigations on the aggregation of phospholipids (mainly phosphatidylcholines) in organic solvents are reviewed and compared with the aggregation behaviour of phospholipids in aqueous medium. In particular we review the data showing that phosphatidylcholines (lecithins) form reverse micellar structures in certain apolar solvents. In these systems not only low molecular weight compounds but also catalytically active enzymes and entire cells can be solubilized. In addition, highly viscous phosphatidylcholine gels can be obtained in organic solvents upon solubilizing a critical amount of water. Generally, phospholipid-based reverse micelles can be regarded as thermodynamically stable models for inverted micellar lipid structures possibly occurring in biological membranes. PMID- 2187626 TI - The isolation of osmotic-remedial conditional lethal mutants of Candida albicans. AB - We have developed a method for the isolation of a broad range of conditional lethal mutants of the pathogenic fungus Candida albicans. The method substantially alleviates the problems posed by the diploid nature, and the biased mutant spectrum, exhibited by most strains of this organism. We have used the method to isolate 560 temperature-sensitive mutants which grew at 30 degrees C but not at 42 degrees C. We identified amongst them a number of osmotic-remedial strains which, at the restrictive temperature, show phenotypes indicating defects in cell wall biosynthesis. PMID- 2187628 TI - Pathophysiology and prevention of acute renal failure: the role of the anaesthetist. AB - Ischaemic renal tubular damage in the perioperative period can lead to acute renal failure (ARF) with a very high mortality rate (60-75 per cent). Recent research suggests that this tubular injury is caused by an imbalance of the oxygen supply and demand of medullary thick ascending limb (mTAL) tubular cells. High oxygen demand is secondary to active reabsorption of solute which is increased in states of intravascular volume depletion. The restricted supply of oxygen is secondary to the organization of blood flow to the inner medulla. Because the vasa recta loop into the inner medulla and a countercurrent exchange process for oxygen is established, the oxygen tension in this area may normally be as low as 10-20 mmHg. In hypoperfusion states, mTAL injury occurs and is exacerbated by intravascular volume depletion, hypoxaemia and endothelial cell swelling which reduces perfusion of these vulnerable and metabolically active mTAL cells. The anaesthetist must prevent or attenuate postoperative renal dysfunction by identifying high-risk patients preoperatively, optimizing intravascular volume status and cardiac output in the perioperative period, as well as responding appropriately to hypoperfusion states. Therapeutic implications relate to this pathophysiological sequence and several physiological and pharmacological considerations are discussed. PMID- 2187629 TI - Regulatory issues during early craniofacial development: a summary. AB - During neurulation, craniofacial structures derived from the first branchial arch are determined to become maxillary, mandibular, and tongue formations. At least four interdependent developmental processes become integrated: (1) allocation of cells into specific lineages (perhaps during gastrulation); (2) regulation of time-dependent differential regulatory and structural gene expressions; (3) positional information resulting in pattern formations; and (4) morphogenesis, histogenesis, and cytodifferentiation. This review highlights progress toward understanding when, where, and how the one-dimensional genetic information encoded within DNA (deoxyribonucleic acid) is sequentially expressed into the embryonic craniofacial complex. Specifically, how might intrinsic autocrine and/or paracrine regulatory factors control the developmental program for early first branchial arch morphogenesis, histogenesis, and cytodifferentiation. Rules learned from normal development should be useful toward advancing the diagnosis, treatment, prognosis, and prevention of congenital craniofacial malformations. PMID- 2187630 TI - Experimental analyses of the migration and cell lineage of avian neural crest cells. AB - Neural crest cells migrate extensively during embryonic development and give rise to numerous and varied derivatives. Two important and unresolved questions are: what controls the migration and differentiation of these cells? This review summarizes recent experiments that address these issues. Specifically, this overview describes the pathways of neural crest cell migration, the functional importance of interactions between neural crest cells and the extracellular matrix for their movement, and studies on neural crest cell lineage in vivo by labelling individual precursor cells. PMID- 2187631 TI - Analysis of human enamel genes: insights into genetic disorders of enamel. AB - A number of inherited craniofacial diseases are known to be associated with gene mutations. Inherited genetic disorders of enamel formation called amelogenesis imperfecta (AI) affect the human population with a prevalence of 1 in 14,000 in the United States. Amelogenins, the major proteins in developing enamel matrix of mammalian teeth, have been suggested to participate in normal enamel matrix biomineralization, as well as with abnormal biomineralization such as seen in AI. The complementary DNA for mouse amelogenin gene (AMEL) has been cloned, characterized, and used as a probe to establish the chromosomal locations of AMEL for mouse and man. The human AMEL gene sequences have been located to the distal short arm p22.1----p22.3 region of the X chromosome, and the pericentromeric region of the Y chromosome. An assignment of human AMEL gene to the X chromosome p22 region together with a recent assignment of the X-linked AI disease locus to the Xp22.2 region support the association of the AMEL-X gene with AI. This also leads us to propose that a mutated AMEL-X gene produces altered amelogenin polypeptide, which is defective in its ability to participate in mineralization of enamel matrix, thus giving rise to the X-linked phenotypes of AI. PMID- 2187632 TI - X chromosome genes involved in the regulation of facial clefting and spina bifida. AB - Congenital malformations such as cleft palate and spina bifida may be multifactorial in etiology. They occur as a result of both environmental agents and defective genes. Consequently it is both practically and intellectually difficult to study their effects experimentally. The advent of molecular biology technology has enabled many genes on the human chromosome to be mapped and some to be cloned. Using these techniques and families that display common congenital malformations inherited in a purely genetic manner, the genetic defects can be separated from the environmental components. This report documents our studies of several families that have cleft palate or spina bifida as X-linked disorders. Their phenotype is similar to the more common multifactorial cases but segregates as a single gene in an X-linked fashion. Localization of these genes using different X chromosome DNA probes and linkage analysis is the first step towards our understanding of the genetic contribution to the etiology of congenital malformations. PMID- 2187633 TI - The neurocristopathies: reinterpretation based upon the mechanism of abnormal morphogenesis. AB - This review sets forth a broadened interpretation of the neurocristopathies based on the current understanding of the role of neural crest cells in normal development. Two general types of cristopathies are defined predicated on the abnormal mechanism involved in production of the defect or condition. Defects and disorders which constitute the originally defined neurocristopathies including pheochromocytoma, neurofibromatosis, and the multiple endocrine adenomatoses are best explained as dysplasias of neural crest derivatives. Affected individuals rarely exhibit true malformation of structure but do carry a lifetime risk for disordered growth of crest derived tissue. On the other hand, defects and disorders which derive from migrational abnormalities primarily of cranial neural crest cells such as frontonasal dysplasia, the DiGeorge sequence, and Waardenberg syndrome represent true malformations. The spectrum of involvement is usually definable at the time of diagnosis and disordered growth of crest derived tissue does not occur. The clinical implications of this distinction are discussed. PMID- 2187634 TI - Evolutionary issues in craniofacial biology. AB - This overview discusses evolution in the context of craniofacial development and developmental processes. It begins with a discussion of the origins of the craniofacial tissues in the dentine and bone of the dermal denticles of the Ordovician jawless vertebrates, followed by a brief discussion of the mechanisms responsible for the evolution of the jaws and the origin of vertebrate dentition. Then the unique neural crest cell origin of the craniofacial skeletogenic and odontogenic tissues is discussed with emphasis on the constancy of rostrocaudal polarization of the skeletogenic cranial neural crest. Given this constancy, the variation in the craniofacial region that occurs across the vertebrates must arise because of epigenetic interactions that evoke the differentiation of craniofacial tissues. These are discussed in the context of epigenetic cascades of epithelial-mesenchymal interactions and how such epigenetic control has itself evolved. Although several mechanisms are considered, emphasis is placed on variation of the timing of development processes (heterochrony). PMID- 2187635 TI - Biochemical correction in the syndrome of hypertension and hyperkalaemia by severe dietary salt restriction suggests renin-aldosterone suppression critical in pathophysiology. AB - 1. Plasma potassium and chloride concentrations were raised and plasma renin activity, aldosterone, bicarbonate and arterial pH were reduced in two brothers with the syndrome of hypertension and hyperkalaemia with normal glomerular filtration rate (Gordon's syndrome), on unrestricted or moderately restricted sodium diets. 2. These abnormalities were corrected in both patients within 10 days of severe sodium restriction. 3. Pressor sensitivity to cold and angiotensin II decreased on low sodium diet, associated with a fall in blood pressure. 4. Increasing distal tubular sodium delivery by infusion of normal saline increased fractional excretion of potassium when aldosterone had been stimulated by severely restricted sodium diet, but not when aldosterone levels were low on unrestricted sodium diet. 5. These findings are consistent with excessive sodium reabsorption as the primary renal lesion in Gordon's syndrome, leading to volume expansion and suppression of renin and aldosterone. Severe dietary sodium restriction leading to volume contraction, by stimulating renin and aldosterone and promoting kaliuresis, corrects the abnormalities. PMID- 2187636 TI - Haemodynamic effects of long-term endothelin infusion in conscious sheep. AB - 1. Synthetic human endothelin-1 was infused intravenously at 15 micrograms/h for 24 h to examine its cardiovascular actions in five conscious sheep. 2. Endothelin produced a maximum increase in mean arterial pressure (MAP) of +8 mmHg at 8 h, with an increase in calculated total peripheral resistance (CTPR) of +2.6 mmHg/L per min, whilst cardiac output (CO) was unchanged. At 24 h MAP was not significantly elevated, however CTPR had increased by +2.8 mmHg/L per min and CO had decreased by 0.9 L/min. 3. This study shows that long-term administration of endothelin produces sustained arterial vasoconstriction in sheep. PMID- 2187637 TI - Occult invasive pituitary adenoma predisposing to fatal bacterial meningitis. AB - Pituitary adenomata are benign neoplasms which usually grow slowly and present with manifestations relating to an associated endocrinopathy or visual disturbance. Rarely these neoplasms will demonstrate a more aggressive behavior with extracranial extension and symptoms of upper airway obstruction or anosmia. Several reported cases suggest that although these neoplasms behave aggressively the overall survival and prognosis for these patients remains good. We present the clinical and postmortem findings of an occult invasive pituitary adenoma leading to the development of bacterial meningitis, coma and death. This communication stresses the necessity for the early diagnosis and treatment of the invasive adenomata to prevent the development of potentially fatal infectious sequelae. PMID- 2187638 TI - Intrasellar primitive neuroectodermal tumor (PNET) in familial retinoblastoma: a variant of "trilateral retinoblastoma". AB - An infant with bilateral familial retinoblastomas was found at age 6 months to have a large mass within the region of the sella turcica. The histology, immunoreactivity and ultrastructure of the tumor showed primitive neuroectodermal cells. A small number of cells showed positive immunostaining to retinal S antigen. This represents a rare form of so-called trilateral retinoblastoma. In most cases of trilateral retinoblastoma, the intracranial non-metastatic tumor is within the pineal gland. The occurrence of such a tumor in the region of sella turcica is very unusual and its possible significance is discussed in regard to our current understanding of the susceptibility to carcinogenesis conferred by inheritance of the mutant retinoblastoma gene, Rb-1. PMID- 2187639 TI - Arterial border zone necrosis of the spinal cord. AB - A 74-year-old man developed necrosis of the spinal cord following an episode of severe hypotension associated with dissection of the aorta. The area of necrosis was confined to the arterial border zone between the anterior and posterior spinal arteries, and involved both gray and white matter symmetrically. The periphery of the cord was spared. Only the lower thoracic cord, which represents a border zone between segmental radicular arteries, was involved. Extensive arterial border zone necrosis was also present in the cerebral cortex and cerebellum. The fact that arterial border zone necrosis is much less common in the spinal cord than in the brain suggests that its development requires a local compromise of the spinal cord circulation in addition to systemic arterial hypotension. PMID- 2187640 TI - Cerebral multiple glio-vascular dysplasias--a case report. AB - We describe the clinical and neuropathologic features of a patient complaining of increased intracranial pressure lasting over two years. Brain CT showed three cystic lesions in the supratentorial regions. Autopsy disclosed multiple small glio vascular abnormalities, in some instances connected with a cystic cavity. The lesions were scattered throughout the white matter of both cerebral hemispheres and suggested a complex dysplasia. PMID- 2187641 TI - Association of primary cerebral lymphoma with meningioma: report of two cases. AB - Two cases of association of primary malignant cerebral non-Hodgkin's lymphoma with clinically silent meningiomas are reported. In one case, the malignant lymphoma of the left frontal lobe was diagnosed radiographically and the small parasagittal meningioma was detected at autopsy. In the other case, both CNS neoplasms, a parasagittal meningioma and a multifocal periventricular and brainstem lymphoma, were only detected at autopsy. In both cases, the small meningiomas were located at the cerebral convexity. The concurrence of the slowly growing meningiomas and the highly malignant cerebral lymphomas, seen in two among about 140 confirmed cases of primary CNS lymphomas, is probably coincidental. No other neoplasms were found outside of the CNS. PMID- 2187642 TI - Atypical (anaplastic) meningioma: relationship between histologic features and recurrence--a clinicopathologic study. AB - Two-hundred-and-eighty meningiomas of the surgical pathological files of the Taipei Veterans General Hospital from the period 1976-1986 were reviewed by the authors without prior knowledge of clinical circumstances or outcome. Thirty-four cases were regarded as atypical or anaplastic based on high cellularity, pleomorphism and the presence of mitotic figures with 6 cases showing only the above features and the remaining 28 displaying in addition one or more of the following "ominous" variables: papillary formation, necrosis and invasion of the underlying brain. With a median follow-up of three years after surgery the recurrence rate was 44% (15 cases) for this group of tumors whereas the remaining 246 histologically benign meningiomas had a 6% recurrence rate during the same period. This difference was statistically significant (p less than 0.0001). Once the atypical or anaplastic character of a meningioma was established, no difference in the recurrence rate was found related to the number of mitoses and whether the additional ominous variables were present, alone or in conjunction with others. Immunostaining for vimentin, S100, fibronectin and EMA showed variable results in the 34 atypical meningiomas but without significant difference between those that recurred within 3 years and the ones that did not. PMID- 2187643 TI - Reverse radioaerosol/radioperfusion distribution in pulmonary endobronchial obstruction. AB - A characteristic image pattern of diminished radioaerosol penetration and reduced radioparticle perfusion has been observed in endobronchial obstruction. This reverse mismatch has a variety of etiologies, with the most common being mucus plugging. The regional hypoxia created by the obstruction causes the blood to shunt from the affected lung. Eleven patients from a group of 178 patients referred with a working diagnosis of pulmonary embolism showed the reversed mismatch. All presented with sudden dyspenea, chest pain and hypoxia. Bronchoscopy was recommended from the image results and nine patients demonstrated mucus plugs that were subsequently aspirated, one patient had a partially obstructing endobronchial carcinoma and one patient had a traumatic fractured bronchus that became occluded with healing granulation tissue. All improved following bronchoscopy. The incompleteness of the airway obstruction accounted for the variations of the perfusion images. Because of the radioaerosol's ability to sharply image the pulmonary airway distribution in contrast to the poor resolution of the radiogases such as xenon-133, it is recommended that radioaerosol lung imaging be substituted for radiogas ventilation imaging since it can accurately detect endobronchial obstruction as well as pulmonary embolism. PMID- 2187644 TI - Cholescintigraphy for assessing the separation potential of thoracoomphalopagus twins. AB - This case report describes the use of cholescintigraphy in the preoperative evaluation of ventrally conjoined twin girls. Sonography and magnetic resonance imaging disclosed an anatomically conjoined heart and a single apparently fused liver. Cholescintigraphy demonstrated that the hepatic system functioned as two independent livers, gallbladders, and biliary drainage systems that were susceptible to separation. PMID- 2187645 TI - Chemoprophylaxis with oral trimethoprim-sulfamethoxazole. In otitis media. Relevance of hematologic abnormalities. PMID- 2187646 TI - Epidemiologic aspects of toilet training. AB - Toilet training is becoming an increasingly important child care issue as child raising becomes an institutional enterprise. This paper reviews the literature of the last 40 years, focusing on the epidemiology of the development of day and night bladder control. The studies indicate that bladder control is usually obtained between 24 months and 48 months of age. Many variations exist between studies, especially the endpoint used to indicate completion of training. Modifying the endpoint used and the related training practices could decrease the age at which children are trained. PMID- 2187647 TI - Abdominal Doppler--current status and future potential. PMID- 2187648 TI - Digital chest radiography: current status. PMID- 2187649 TI - Pre-operative localisation in primary hyperparathyroidism. AB - One hundred and seventy-three patients operated on for primary hyperparathyroidism over a four year period by one experienced surgeon are reviewed. An overall success rate of 98.8% was achieved with information from pre operative localisation using ultrasound and parathyroid venography with sampling. Parathyroid ultrasound was heavily dependent on the experience of the operator. An experienced ultrasonologist detected 63% of solitary adenomas and correctly localised the site of 82%. Glands were not detected if they were of small size or in an inaccessible site. He identified all those enlarged glands over 0.36 grams in weight that were lying in the usual site. In contrast, inexperienced ultrasonologists had a detection rate of 20%. Parathyroid venography with sampling detected a single site of excess hormone production in the neck of 79% of patients with a single adenoma, and correctly localised the site in 75% of these. The side was correctly predicted for 63% of glands, the level was correctly predicted for 56% and both side and level localisations were correct in 44%. Multi-gland disease was correctly suggested by the experienced ultrasonologist in 56% of cases and by parathyroid venography with sampling in 31% cases. PMID- 2187650 TI - Acquired cystic disease of the kidney: ultrasound as the primary screening procedure. AB - Patients with end-stage renal disease on long term dialysis may develop de novo renal cystic disease. We used ultrasound as a primary screening procedure for renal cysts in 71 patients. In seven patients (10%) the native kidneys could not be identified. In 35 patients renal cysts were identified indicating a prevalence of acquired renal cystic disease of 49%. PMID- 2187651 TI - A double blind clinical study comparing the safety, tolerance and efficacy of ioversol 240 and iohexol 240 (Omnipaque 240) in ascending venography. AB - A randomised, double blind, parallel group study was performed comparing the efficacy, tolerance and safety of ioversol-240 and iohexol-240 (Omnipaque-240) in 50 patients undergoing venography. Adult patients of either sex, 18 years of age or older, who were referred to the Department of Radiology at Northwick Park Hospital, Harrow, England, for ascending venography were study candidates. There were 25 patients in each drug group, who were comparable in relation to age, sex, weight, height and race. The drug groups were comparable with respect to contrast volume and iodine dose administered. All film sets were rated as diagnostic and the patient groups were comparable with respect to quality of procedure. The incidence of patients reporting heat and pain as a result of the injection of contrast medium was minimal and comparable in the drug groups. Safety was assessed by monitoring vital signs (blood pressure, pulse and respiration), clinical laboratory studies and observation of adverse effects prior to and after injection of contrast medium. Vital signs remained stable in all study patients. There were no abnormal post-procedural laboratory data which were judged to have been drug related. There were no drug related adverse effects in either group. It is concluded that ioversol-240 is a safe, well-tolerated and effective contrast agent when used for venography. PMID- 2187652 TI - Ultrasonic and comparative angiographic appearances of a spontaneous aorto-caval fistula. AB - A 71-year-old man with an atherosclerotic abdominal aortic aneurysm developed a spontaneous aorto-caval fistula. The ultrasound appearances showing a direct fistulous communication between the inferior vena cava and the aorta are presented and these are correlated with the angiographic appearances. PMID- 2187653 TI - The sonographic appearance of cyclophosphamide-induced acute haemorrhagic cystitis. AB - The ultrasound findings in a case of cyclophosphamide-induced acute haemorrhagic cystitis are reported. Radiologists should be familiar with these findings as the drug is used widely and the complication is not infrequent. PMID- 2187654 TI - Knowing, valuing, acting: clues to revising the biopsychosocial model. AB - While remaining influential in education and research in psychiatry and medicine, the biopsychosocial (BPS) model has been criticized for ambiguity in conceptualizing everyday clinical problems. As a multilevel general systems approach, it leaves obscure which system level (cellular, person, family, community, and so on) is most clinically important at any point in time. As a model for psychiatry and medicine, it does not address the practical and moral dimensions of clinical work. This report reviews criticisms and concerns about the BPS model. These criticisms are used to begin a more practicable revision of the model. PMID- 2187655 TI - Insulin-dependent diabetes mellitus and eating disorders: a prevalence study. AB - There have been numerous reports in the recent literature suggesting a relationship between diabetes mellitus and the eating disorders. In the current investigation, 97 pediatric diabetes patients were administered a modified version of the Eating Habits Questionnaire, which included items specific to diabetes mellitus based on DSM-III-R criteria. None of this sample were diagnosed as anorexic and only one patient was diagnosed as currently bulimic. Possible reasons for the higher prevalence rates reported for other samples are discussed. PMID- 2187656 TI - The combination of lithium and carbamazepine in treatment and prevention of manic depressive disorder: a review and a case report. AB - The action of carbamazepine (CZP) is similar to that of lithium with regard to therapeutic effect towards mania; in addition, it has a certain effect towards endogenous depression. Furthermore, CZP has a prophylactic effect towards manic depressive mood swings, although probably not as expressed as that of lithium. In some cases, especially in rapid-cyclers, neither CZP nor lithium have this effect when applied separately, whereas the combination of the two drugs is effective in some cases. A review of the relevant literature, as well as an illustrative case history, is presented. PMID- 2187657 TI - Current status of 24-hour ambulatory blood pressure monitoring in clinical practice. AB - Twenty-four-hour monitoring of blood pressure (BP) is a new non-invasive technique of examination which, apart from becoming a useful research tool, has found widespread use in clinical practice. Monitoring detects BP fluctuations due to changes in physical and mental activities throughout the day and to physiological circadian rhythms, especially the nocturnal BP decrease. Monitored BP shows a better correlation with the degree of target organ damage than casual BP. In patients with increased BP values persisting despite therapy, BP monitoring makes it possible to differentiate hypertensives with truly resistant or inadequately treated hypertension from those showing substantially higher BP values in the doctor's office than their normal daytime levels are. BP monitoring may improve the accuracy of prediction of cardiovascular complications. This fact, however, has to be verified by other prospective studies which may expand the range of potential applications of this new method. PMID- 2187658 TI - Applications of computers in surgery. PMID- 2187659 TI - Cytolytic activity of human natural killer cell subpopulations isolated by four color immunofluorescence flow cytometric cell sorting. AB - The natural killer activity and phenotypic properties of six different subpopulations of normal human peripheral blood lymphocytes obtained by four color immunofluorescence cell sorting were examined. Phycoerythrin-conjugated CD16 and CD56 were used simultaneously to identify (CD16 + CD56+) NK cells. The cells most effective in mediating NK cytolysis against K562 target cells were CD3 (16 + 56+)57 -8+. Although most of the K562 killing was found in the CD3-(16 + 56 +) groups of cells, a substantial degree of NK activity was detected in the CD3+(16 + 56 +) subpopulations of some individuals. The level of expression of CD57 and CD8 was significantly higher on CD3+(16 + 56 +) than on CD3-(16 + 56 +) cells. PMID- 2187660 TI - New drug for AIDS and advanced ARC patients. PMID- 2187661 TI - Hypervariable region 5'-flanking [Leu A3]insulin gene of insulin Tochigi is different from those of insulin Wakayama I,II. AB - Three families with abnormal insulinemia have been reported in Japan and sequencing analysis revealed that they had the same point mutation in one allele of the insulin genes causing [Leu A3]insulin. To estimate whether or not this same mutation came from a common ancestor we determined the sequence of the hypervariable region 5'-flanking the third [Leu A3]insulin allele (insulin Tochigi). This region is composed of 42 tandem repeating oligonucleotides, is 599 base pairs long and the sequence is 5' cdi jfa faa aba baa aaa fab aaa caa aac aca cba aaf ccb 3' (abbreviated as a = ACAGGGGTGTGGGG; b = ACAGGGGTCTGGGG; c = ACAGGGGTCCTGGGG; d = ACAGGGGTCCGGGG; f = ACAGGGGTCCCGGGG; i = ACAGGGTCCTGGGG; j = ACAGGGGTGTGAGG). The length of this region is different from those of the first and second [Leu A3]insulin alleles (insulin Wakayama I,II). This difference suggests either that insulin Tochigi and insulin Wakayama I,II are not of the same origin, or that three cases of [Leu A3]insulin in Japan have the same ancestor but recombination has occurred in this region at some point in the past. PMID- 2187662 TI - The effect of ovarian function on insulin-like growth factor I plasma levels and hepatic IGF-I mRNA levels in diabetic rats treated with insulin. AB - When insulin was administered to streptozotocin-induced diabetic female rats, the percentage of glycohemoglobin, growth rate, ovulatory cycle, uterus to body weight ratio, and insulin-like growth factor (IGF-I) level returned to near normal. In untreated diabetic rats there were no normal estrous cycles, and hepatic IGF-I mRNA (7.94 +/- 1.02 O.D. units per micrograms total RNA) levels were significantly lower than the control or insulin-treated groups in proestrus (16.47 +/- 0.91 and 17.15 +/- 1.84, respectively). Insulin therapy restored the hypothalamic-pituitary-ovarian axis with the reinstitution of normal estrous cycles. Plasma IGF-I levels were highest in non-diabetic proestrous animals (277 +/- 36.9 ng/ml), significantly higher than IGF-I levels in insulin-treated diabetic rats in diestrus (174 +/- 23.1 ng/ml), non-diabetic diestrus rats (165 +/- 18.4 ng/ml) and untreated diabetic rats (135 +/- 19.7 ng/ml). Plasma IGF-I levels were elevated in insulin-treated diabetic rats in proestrus (221 +/- 78.3 ng/ml), however this was not significantly different from any other group. The increases observed in plasma IGF-I and hepatic IGF-I mRNA after insulin therapy correlate with the normalization of sex hormone secretion. Though this study does not prove a causal relationship between restoration of ovarian function and normalization of circulating IGF-I levels, a relationship has been established, as evidenced by higher levels of IGF-I in both the control and insulin-treated diabetic proestrous groups when compared to the diestrus groups. PMID- 2187663 TI - Development of carbohydrate intolerance in offspring of Asian Indian conjugal type 2 diabetic parents. AB - Sixty-four offspring of conjugal diabetic parents (OCDP) who were normoglycaemic initially were available for a retest after a period of 4-9 years. Among them 10 (15.6%) had developed diabetes, 19 (29.7%) had developed IGT and the remaining 35 (54.7%) had maintained normal GTT. The predictive value of the baseline (initial) parameters was tested. Among the non-obese OCDP (BMI less than 25 and less than 27 for women and men, respectively), the initial sum of plasma glucose (sigma PG), and the mean increment of insulin during GTT (delta IRI), and the 2-h IRI values were higher in the group that developed abnormal glucose tolerance (P less than 0.05 compared to controls and normal OCDP). They also had higher insulin:glucose ratios, indicating higher insulin output for a given glucose concentration. On the other hand, among the obese OCDP the initial parameters did not differ between those who developed abnormal glucose tolerance and those who did not. Stepwise multiple regression analysis showed that the baseline sigma plasma glucose value was significantly related to the final 2-h plasma glucose when all the OCDP were taken together (P = 0.0023) and also in the non-obese OCDP (P = 0.0002). The other parameter which showed a relation to the final 2-h plasma glucose was the baseline delta IRI, although it was not statistically significant (P = 0.08). No such relation was observed in the obese group. PMID- 2187664 TI - Transepidermal water loss and skin surface hydration in the non invasive assessment of stratum corneum function. AB - Transepidermal water loss (TEWL) and water content of the stratum corneum, when measured simultaneously, provide important information regarding skin function. On the basis of the model presented, it is possible to differentiate dry senile skin from dry pathological skin (such as psoriasis, atopic dermatitis, irritant reaction), clinically involved or uninvolved. Pathological dry skin, because of the impaired barrier function is associated with increased TEWL and low corneum water content. Senile skin, on the other hand, shows both, decreased TEWL and stratum corneum water content. It is suggested that with this model it may be possible to differentiate uninvolved pathologic from healthy skin. PMID- 2187666 TI - [Medial tarsal tunnel syndrome]. PMID- 2187665 TI - [Psychotropic effects of captopril? Effect of a short-term treatment on reaction and concentration capabilities and space perception ability]. AB - In a randomized, placebo-controlled double-blind trial 22 healthy normotensive young men (mean age 25 +/- 1.7 years) were given a single oral dose of 50 mg captopril or a placebo (11 subjects each). To test their concentration and proficiency, as well as spatial perception and reaction capacity four tests were administered: attention, concentration, hose-pattern perception and "Bonn Determination Device". Captopril had no negative effects on any test performances either one or five hours after its administration, or after a single daily dose for seven days. There was only a small, statistically not significant, difference in the effect on blood pressure between captopril and the placebo. PMID- 2187667 TI - [Pathogenesis and therapy of obesity. How do we protect ourselves from abundance?]. PMID- 2187668 TI - [The thrombolysis treatment of acute myocardial infarct at the site of the emergency. A randomized double-blind study]. AB - Two million units of urokinase were administered intravenously as a bolus, either before (group I, n = 40) or after hospital admission (group II, n = 38), to 66 men and 12 women (mean age 55 +/- 8 years) with typical symptoms of acute myocardial infarction of less than 4 hours' duration. Time elapsed between onset of symptoms and urokinase administration averaged 85 +/- 51 min for group I and 137 +/- 50 min for group II (P less than 0.005). The complication rate was low, both during the pre-hospital and the hospital phases, without any significant differences between the two groups. The rate of open infarct vessels (by angiography before discharge from hospital) was 61% for group I and 67% for group II (no significant difference). Global left ventricular function, regional wall motion in the infarct area and maximal creatinekinase values did not significantly differ between the two groups (ejection fraction 51 +/- 10% and 53 +/- 14%, respectively; creatinekinase 838 +/- 634 U/l and 924 +/- 595 U/l, respectively). The data indicate that thrombolytic pre-hospital treatment carried a low risk. The gain of 45 min, however, seems to be of secondary importance in any significant diminution of the acute infarction size. PMID- 2187669 TI - [Ultrasonically guided fine-needle puncture. The limits of the method in the abdomen and retroperitoneal space]. AB - The sensitivity and specificity of ultrasound-directed fine-needle biopsy in the differentiation of malignancy or otherwise of structures in the abdomen or retroperitoneal space which look suspicious on ultrasound was evaluated from results in 558 patients (306 men, 252 women). Data from two different centres were used to characterize further the influence of different techniques of puncture, cytopathologists and groups of patients on the validity of the examination. Sensitivity (in the two centres) was 88 and 80%, respectively, specificity 100 and 99%. The validity of the examination was the same at both centres. In both centres the sensitivity was worst for pancreatic tissue, at only 72 and 61% respectively, compared with other organs (e.g. liver, lymph nodes, kidney) (P less than 0.05). Fine-needle biopsy of abdominal and retroperitoneal organs will thus be subject to a not insignificant number of false-negative results of cytological examination. PMID- 2187670 TI - [The diagnosis and therapy of exogenous allergic alveolitis]. PMID- 2187671 TI - [Modern methods for controlling type-1 diabetes?]. PMID- 2187672 TI - How embryos work: a comparative view of diverse modes of cell fate specification. AB - Embryonic processes in the nematode C. elegans, the gastropod mollusc Ilyanassa, the dipteran Drosophila, the echinoid Strongylocentrotus purpuratus, the ascidian Ciona, the anuran Xenopus, the teleost Brachydanio and mouse are compared with respect to a series of parameters such as invariant or variable cleavage, the means by which the embryonic axes are set up, egg anisotropies and reliance on conditional or on autonomous specification processes. A molecular interpretation of these modes of specification of cell fate in the embryo is proposed, in terms of spatial modifications of gene regulatory factors. On this basis, classically defined phenomena such as regulative development and cytoplasmic localization can be interpreted at a mechanistic level, and the enormous differences between different forms of embryogenesis in the Animal Kingdom can be considered within a common mechanistic framework. Differential spatial expression of histospecific genes is considered in terms of the structure of the gene regulatory network that will be required in embryos that utilize cell-cell interaction, autonomous vs conditional specification and maternal spatial information to differing extents. It is concluded that the regulatory architectures according to which the programs of gene expression are organized are special to each form of development, and that common regulatory principles are to be found only at lower levels, such as those at which the control regions of histospecific structural genes operate. PMID- 2187673 TI - Insulin and insulin-like growth factor I (IGF I) in early mouse embryogenesis. AB - Growth factors have an important role in the regulation of cell growth, division and differentiation. They are also involved in the regulation of embryonic growth and differentiation. Insulin and insulin-like growth factor I (IGF I) play an important part in these events in the later stages of embryogenesis, when organogenesis is completed. In this study, we are presenting evidence that insulin and IGF I are also secreted by embryonic tissues during the prepancreatic stage of mouse development. We found measurable amounts of insulin and IGF I in 8 to 12-day-old mouse embryos. We also showed that embryonic cells derived from 8 , 9- and 10-day-old mouse embryos secrete insulin, IGF I and/or related molecules. Furthermore, the same growth factors, when added to the culture of 9 day-old mouse embryonic cells, stimulate their proliferation. These results lead to the conclusion that insulin can stimulate the growth of embryonic cells during the period when pancreas is not yet formed, which is indirect evidence for a paracrine (or autocrine) type of action. PMID- 2187674 TI - Maternal messenger RNA distribution in silkmoth eggs. I. Clone Ec4B is associated with the cortical cytoskeleton. AB - We have constructed a cDNA library from mature egg RNA of the silkmoth, Hyalophora cecropia. Differential screening of the library using cDNA made against mRNAs from the yolky cytoplasm (soluble fraction) and the cortical cytoplasm (cytoskeletal-associated or cortical fraction) resulted in several clones that hybridized to a higher degree to the cDNA from the cytoskeletal associated fraction. We selected and analyzed the clone giving the strongest signal (designated Ec4b) for its distribution in situ and found that it bound to mRNAs in the nurse cell cytoplasm, in the cortex and in the follicle cells of oocytes. Hybridization of the insert from Ec4b to both detergent-soluble and insoluble (cortical) RNA on dot blots further supported the observation that the mRNA corresponding to Ec4b was enriched in this cytoskeletal fraction. The mRNA for Ec4b was approximately 500 bases long and the gene seems to be a member of a large multigene family in the H. cecropia genome. Analyses of the nucleotide and amino acid sequences reveal similarity to lepidopteran chorion genes and a lesser but convincing similarity to vertebrate cytokeratins. The filter and in situ hybridization data point to the association of specific messenger RNAs with the cortical cytoskeleton of silkmoth oocytes. Aspects of the structure of the protein encoded by this mRNA suggest that it is a structural component necessary for formation of the cellular blastoderm of the embryo. The association of this maternal mRNA with the cortical cytoskeleton presents the interesting possibility that mRNA bound to the cytoskeleton may be capable of participating in the synthesis of new cytoskeleton or related structures during blastoderm formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2187675 TI - Developmental expression of the creatine kinase isozyme system of Xenopus: maternally derived CK-IV isoform persists far beyond the degradation of its maternal mRNA and into the zygotic expression period. AB - The differential expression of the multilocus CK isozyme system throughout development of the two Xenopus species X. laevis and X. borealis was investigated. A cDNA containing the nearly complete coding sequence of the CK-IV subunit of X. laevis was isolated and sequenced. Early development of X. laevis proceeds with a stock of maternally derived CK-IV/IV isozyme. While the mRNA declines rapidly after fertilization and disappears before neurulation, maternal CK-IV/IV isozyme is active far beyond the onset of zygotic expression and is still detectable when tadpoles start feeding. Zygotic expression of CK-IV begins after neurulation, at stage 22/24, and seems to start simultaneously with that of another gene, CK-III. Modulation in the expression of these two genes and the appearance of two other isoforms, the CK-I and CK-II/III isozymes, take place during development in a tissue-specific manner. During metamorphosis, the CK phenotypes of eyes and skeletal musculature undergo additional changes. The final adult pattern only appears several weeks after metamorphosis. The presumed orthologous CK isozymes of X. borealis show a developmental profile similar to that of X. laevis, except that CK-II/II is equally present in oocytes and during early development, in addition to CK-IV/IV isozyme. These results show that the expression of each of the four CK genes of Xenopus is under differential developmental control. PMID- 2187676 TI - [Strategic focus for the development of human resources]. PMID- 2187677 TI - Ethical issues in geriatric emergency medicine. AB - The emergence of ethics, geriatrics, and emergency medicine as areas of specialized interest has proceeded rapidly over the past two decades. Each of these fields continues to grow in response to patient needs, but it is clear that scientific knowledge alone cannot provide the physician with all the guidance necessary to ensure the provision of optimal care. Patient care cannot consist only of making diagnoses, prescribing medications, and performing technical procedures. Particularly in the care of the elderly, the emergency physician must be able to recognize ethical issues and to respond to them in the manner that will provide the greatest benefit to the patient. With the application of such skills, the emergency treatment of the elderly promises more benefit for elderly patients and their families and less doubt and anguish for emergency practitioners. PMID- 2187678 TI - Bacterial pneumonia in the elderly. AB - Bacterial pneumonia is among the most frequent diagnoses that bring elderly patients to the Emergency Department. The morbidity and mortality subsequent to these infections is very high among these individuals, and presenting symptoms and signs may be subtle. Gram-negative bacilli, H. influenzae, and mixed organisms more commonly cause lower respiratory tract infections in this population. The diagnosis and management of nursing home and community-acquired pneumonias are reviewed, as are important preventative strategies. PMID- 2187679 TI - Geriatric emergency clinical pharmacology. AB - Drugs associated with elderly individuals seen in the Emergency Department must be understood both as causal or etiologic agents of certain common presentations and as therapeutic tools. Special problems of the elderly include their increased frequency and altered patterns of drug use as compared with younger persons. They are predisposed to problems with certain drugs because of altered hepatic blood flow, renal clearance, body composition, sensitivities, and compliance that result from age. Most important, the practitioner is now provided with a set of resources, including lists of common presentations in the Emergency Department and specific drugs that must be considered to be potential etiologic or causative agents for that presentation. In addition, therapeutic agents for both physicians and elderly patients are presented in catechism. PMID- 2187680 TI - Laboratory values in the elderly. Are they different? AB - Diseases do not always show the usual or "classic" signs and symptoms in the elderly. Physiologic changes over the years of a long life seem to be responsible for impairment of regulation or function of many organ systems. Since function often is measured in clinical medicine by laboratory testing, physicians frequently face difficult clinical decisions as to the need for further evaluation of a patient based upon a laboratory test result received. For the most part, the laboratory values obtained in elderly persons seem to fall into our traditional or so-called normal ranges, and little evidence supports the need for separate sets of reference ranges for the elderly. A few patients do show abnormalities on specific tests, and a few test values can be expected more frequently than others to be out of line in healthy elderly individuals, specifically: serum alkaline phosphatase (elevations to about 2.5 times the normal) fasting blood glucose (up to 135 to 150 mg/dl) postprandial blood glucose or oral glucose tolerance test (increased above normal to 10 mg/dl per decade of age) normal serum creatinine with the existence of markedly decreased creatinine clearance higher erythrocyte sedimentation rates (up to 40 mm/hr) hemoglobin (lowest acceptable level is 11.0 gm/dl in women; 11.5 gm/dl in men) BUN (up to 28 to 35 mg/dl) The presence of multiple diseases in elderly patients, as well as the many medications often taken, will no doubt be more of a source of confusion and consternation in the clinical correlation of laboratory test results than the lack of adequate reference ranges specifically compiled for the elderly. The question "What test result is significant and raises suspicion of disease?" will remain a part of that all-important integration and correlation of the information available to the physician for the diagnosis and treatment of the patient. PMID- 2187681 TI - Delirium in the elderly. AB - Delirium, an acute confusional state, is an organic brain syndrome that manifests deficits in attention, irrelevant or rambling speech, and other cognitive deficits. Its symptoms often fluctuate over the course of the day, and patients may be hyperactive--for example, restless and screaming--or hypoactive--for example, quiet, inactive, and stuporous. Occurring in approximately 20% of hospitalized elderly patients, delirium is the most common psychiatric syndrome in acutely ill general medical and surgical patients. Fifteen to 30% of delirious patients expire, and others are prone to a variety of complications: falls, pressure ulcers, oversedation, dehydration, and others. Almost any acute illness can cause delirium in the elderly, but the most common offenders are acute infections and drugs. Many patients have a pre-existing dementia. The first step in arriving at a correct diagnosis is to distinguish delirium from other psychiatric syndromes that can cause confusion, such as dementia, depression, schizophrenia, and mania. Once delirium is established, a comprehensive general examination and a mental status examination is required. Routine laboratory and radiologic tests are directed at the common metabolic and infectious disorders that precipitate delirium. Treatment is directed at the underlying acute illness. In all patients, it is important (1) to treat the underlying acute illness, (2) to provide appropriate fluid and electrolytes, (3) to discontinue any unnecessary drugs, and (4) to allay the patient's fear and agitation through the use of simple, repetitive instructions, orientation cues, and by limiting the use of physical restraints. If psychotropic medications are needed to treat psychotic symptoms, to prevent patients from harming themselves or others, or to facilitate necessary diagnostic and therapeutic interventions, then haloperidol is the drug of choice in most instances. Drugs with anticholinergic properties should be avoided. PMID- 2187682 TI - Stroke intervention. AB - As current stroke therapies are refined and newer promising methodologies brought on line, the rapid, accurate diagnosis of stroke syndromes will become more important. The emergency department is in a unique and vital position for providing early diagnosis, for organizing and activating an interdisciplinary team to rapidly assess the stroke patient, and for establishing protocols for therapy. The emergency physician has an important role in increasing general awareness and in helping to educate the public about risk factors and early symptoms of various stroke syndromes. Nursing and emergency personnel must also be made increasingly aware of the desirability of early recognition of stroke and of new therapeutic measures. Stroke patients should no longer be considered of moderate to low priority, as has often been the case in the past. With an aggressive approach in dealing with risk factors, education in early recognition of symptoms, and new and promising interventional therapies, morbidity and mortality from this often catastrophic disease may be dramatically reduced. PMID- 2187683 TI - Subdural hematoma in the elderly. AB - The presentation of subdural hematoma is often more subtle in the elderly than in younger patients, due in part to cerebral atrophy and in part to the interaction with other medical conditions to which the elderly are prone. With the advent of computed tomography, the diagnosis of subdural hematoma has become easier and noninvasive. This improvement in diagnostic capability has enhanced the understanding of the epidemiology and presentation of subdural hematomas in the elderly. The role of magnetic resonance imaging is also discussed, as is the pathophysiology, management, and prognosis in the elderly patient. PMID- 2187684 TI - Dizziness and fainting in the elderly. AB - Syncope, vertigo, and related conditions are common in the elderly and must be evaluated carefully. There is major potential for treatable life-threatening conditions, falls with injury, and simply a fearful, confining, and unpleasant existence. The ability to evaluate and manage comfortably and confidently the elderly patient with dizziness and fainting is a major measure of the skill and maturity of an emergency physician. PMID- 2187685 TI - Falls in the elderly. AB - Finally, we conclude with a reminder that the causes of falls in the elderly are multifactorial and that some of these factors may be summative. Most falls result from interaction of intrinsic and extrinsic (environmental) factors. In the Emergency Department, it is very important to take a detailed history of the circumstances leading to the fall and to perform a thorough physical examination. Every attempt should be made to identify predisposing factors for the fall and for preventive measures to be initiated. These may include geriatric consultation or a home visit to evaluate home environment. There is a great need for additional research in this field. Falls are one of the syndromes common in the elderly that deserve more careful attention and are considered amenable to both primary and secondary prevention measures. PMID- 2187686 TI - Orthopedic trauma in the elderly. AB - The bones of elderly individuals fracture easily. The fractures in osteoporotic bones may not be easily identified on plain films. A high level of suspicion will result in more accurate diagnosis and appropriate referral and treatment of these patients. PMID- 2187687 TI - Acute rheumatologic disorders in the elderly. AB - A variety of rheumatologic disorders affect the elderly. Some of these problems are seen almost exclusively in the elderly, such as temporal arteritis and pseudogout. Because of underlying chronic diseases, these patients are also at increased risk for joint infection and resultant sepsis. Evaluation of synovial fluid from the inflamed joint is important. Light microscopy evaluation with a red polarizing compensator can help diagnose crystal-mediated disease, such as gout or pseudogout. Examination of Gram stains can help diagnose infectious arthritis. Thus, appropriate processing of synovial fluid is mandatory for the diagnosis of many rheumatologic disorders that occur in the elderly. A variety of metabolic disorders are associated with pseudogout and should be searched for on laboratory evaluation. Appropriate laboratory evaluation and follow-up following the acute episode are important in the care of these patients. For example, temporal arteritis with resultant blindness is a feared disorder in the elderly. Transient blindness, headaches, jaw claudication, and an elevated Westergren sedimentation rate suggest this diagnosis. Aches and pain in the neck and shoulder area, especially in the morning, are typical of polymyalgia rheumatica. Polymyalgia rheumatica may also be a symptom of temporal arteritis. PMID- 2187688 TI - Imaging considerations in the geriatric emergency department patient. AB - This article has reviewed the imaging modalities for clinical problems that are prevalent or problematic in the geriatric Emergency Department population. Geriatric patients may present with atypical symptoms that mask serious illness: diagnostic imaging begins with a high index of suspicion and the choice of the proper imaging modality. For certain problems, such as skeletal trauma and chest complaints, conventional radiography provides an excellent screening examination. For other problems--abdominal, vascular, and central nervous system disorders- computed tomography, ultrasound, and radionuclide scanning have become important primary imaging modalities. Since the emergency physician is in a position to direct the initial imaging of the patient, he or she must weight the factors of cost, invasiveness, and accuracy of the diagnostic modalities available at the institution. Emergency radiology is a growing field. References have been included in the reference list for general emergency radiology, specific modalities, and specific anatomic areas. In addition, there are resources that document pitfalls in imaging; the Keats volume is indispensable both in the Emergency Department and in the Radiology Department. PMID- 2187689 TI - Surgical emergencies of the abdomen. AB - Abdominal emergencies in the elderly requiring emergent surgery pose a significant challenge to the emergency physician. Because of concomitant illness, these patients generally have a substantial operative risk. Further, the symptoms and signs in these patients are frequently milder and less specific than in younger adults with the same conditions. Therefore, the emergency physician must develop a high index of suspicion for these conditions and must seek early surgical consultation, even if a definitive diagnosis has not been established. In other words, in many cases consultation must be sought on the basis of the emergency physician's clinical suspicion rather than on "hard" data. Emergency physicians must pay particular attention to associated extra-abdominal disease, which must be diagnosed and stabilized to minimize the risk of emergent surgery. Only aggressive assessment, expeditious resuscitation, and team work with the surgical consultants can minimize the high mortality rate associated with these acute abdominal surgical emergencies. PMID- 2187690 TI - Multiple trauma and the elderly patient. AB - The elderly patient is likely to suffer severer immediate effects and more long term complications from equivalent forces of injury. However, with an aggressive approach to evaluation, monitoring, and treatment, there is hope for successful recovery in the majority of cases. PMID- 2187691 TI - Burns in the elderly patient. AB - Whether in the prehospital setting or in the Emergency Department, the emergency physician is usually the first care-giver to the burned elderly patient. Though the predominance of care over the long-term is by burn specialists, attention to the details of resuscitation and stabilization by the emergency physician in the initial stages has a vital role in the overall scheme of care. PMID- 2187692 TI - Psychiatric emergencies in the elderly. AB - Psychiatric disorders are best managed by interdisciplinary teams of psychiatrists, psychiatric nurses, social workers, and psychologists. Some Emergency Departments have access to such psychiatric services either in the hospital or in associated clinics or community mental health centers. Unfortunately, many are not staffed with mental health professionals or such expertise is available only on a limited basis, particularly on evenings and weekends. Therefore, one or more members of the Emergency Department staff should have specialized psychiatric training and experience. We have reviewed the format for conducting a psychiatric history and mental status examination and have discussed the most common emergency psychiatric disorders of the elderly and their management in the Emergency Department. In order to assess and treat elderly psychiatric patients properly, emergency personnel must be aware of the medical disorders associated with psychiatric illness and must be prepared to initiate treatment quickly and appropriately. For most patients, emergency intervention is the first step in ensuring that a correct diagnosis is made and that ongoing psychiatric treatment is arranged through timely consultation and referral. PMID- 2187693 TI - Social emergencies in the elderly. AB - An examination of the social concerns of the elderly reinforces the importance of a thorough social assessment and the availability of skilled staff in an Emergency Department to make appropriate community referrals. The resolution of disposition problems brought about through caregiver exhaustion, patients no longer able to care for themselves in the community, and abandonment by individuals and institutions require a complex array of skills. The serious problem of drug and alcohol abuse among the elderly must be recognized by Emergency Department staff. Physical problems often disguise the existence of a problem of substance abuse. Clinicians in the Emergency Department should evaluate elderly patients using social and family history information in addition to a thorough physical assessment. Elder abuse manifests as physical abuse, psychological abuse, material abuse, and active and passive neglect. The problem is growing, and there is a need for skilled observation and detection of elderly patients presenting for emergency care. As the proportion of the elderly population in this country increases, social policies and program development must reflect these changes. Experts in fields such as gerontology, geriatric medicine, psychiatry, nursing, and social work must make recommendations for changes in the medical and social service delivery systems. The availability of coordinated, comprehensive services for the elderly will expand as the movement toward geriatric treatment centers grows. These centers will provide medical, psychiatric, social, and residential care through the concept of a continuum of care. They will employ a multidisciplinary team of geriatric specialists and include outreach as well as treatment services. Communities with a geriatric treatment center provide a valuable resource for patients identified through Emergency Department visits. The Emergency Department must play an active role in assisting hospitals, area agencies on aging, and other concerned members of the community plan programs for elderly patients with physical and social concerns. While these changes are implemented, the Emergency Department will continue to remain responsive to the social concerns of the elderly through deliberate organizational efforts designed to maintain a high quality of care for elderly patients. PMID- 2187694 TI - Experimental evaluation of rehabilitation in chronic obstructive pulmonary disease: short-term effects on exercise endurance and health status. AB - Randomly assigned 119 adults with chronic obstructive pulmonary disease to an 8 week comprehensive rehabilitation program or to an 8-week education control program. Comprehensive pulmonary rehabilitation included education, physical and respiratory therapy instruction, psychosocial support, and supervised exercise training; education control included biweekly classroom instruction and discussions on respiratory therapy, medical aspects of lung disease, clinical pharmacology, and diet, but no exercise training. Both groups received extensive physiological and psychosocial evaluation before and after the intervention. Six months after enrollment, patients randomly assigned to the rehabilitation program showed significant increases in exercise endurance, whereas patients randomly assigned to control program showed nonsignificant increases. Improvement in self efficacy was correlated with improvements in exercise endurance. PMID- 2187695 TI - Attributions for dietary failures: problems reported by participants in the Hypertension Prevention Trial. AB - Assigned participants in the Hypertension Prevention Trial to one of four diets for a period of 3 years: (a) weight loss, (b) reduced sodium, (c) weight loss plus reduced sodium, and (d) reduced sodium plus increased potassium. At 6-month intervals, they reported problems they were having adhering to their diets. Problem attributions were coded along the dimensions of internality, stability, and controllability and were categorized as intrapersonal or extrapersonal. Attributions were found to differ by type of diet and sex of participant. Participants assigned to weight-loss groups were significantly more likely than those assigned to non-weight-loss groups to blame themselves for their problems with adherence, making characterological as opposed to external or situational attributions. Men perceived problems to be more controllable than women. Attributions did not predict weight loss, change in urinary sodium, or change in potassium excretion. PMID- 2187696 TI - Free flow electrophoresis for the purification of proteins: I. Zone electrophoresis and isotachophoresis. AB - The principles and some applications of free flow zone electrophoresis and isotachophoresis are described. The influence of (i) carrier electrolyte conductivity on the migration velocity and (ii) band shape on zone electrophoresis was investigated. The technique was found convenient for studying the effect of pH on the mobility of proteins to create a mobility curve. The purification of alcohol dehydrogenase from a crude yeast extract revealed the separation power of zone electrophoresis for complex protein mixtures. Without additional steps, a purification factor of 5.4, with a recovery of 97% alcohol dehydrogenase, was achieved. Free flow isotachophoresis was applied to the purification of immunoglobulins from human serum. Disadvantages of this technique are the time-consuming development of an optimized separation system and the empirical search for suitable spacers. Also, reaching of the steady state becomes increasingly difficult as the number of sample components increases. PMID- 2187697 TI - Panencephalopathic type of Creutzfeldt-Jakob disease with primary extensive involvement of white matter. AB - The case of a 66-year-old woman with atypical Creutzfeldt-Jacob disease (CJD) presents several peculiarities. Pathologic examination confirmed a rare CJD case with primary generalized spongiform changes of the white matter and only moderate, but typical changes of the gray matter. Besides an essentially typical clinical course, the patient developed temporary diplopia and vertical eye movement paralysis. Intoxication had been excluded. Isoelectric focusing revealed oligoclonal CSF-IgG. Magnetic resonance imaging studies showed periventricular accentuated flat and striped hyperintense structures. EEG had CJD-typical periodic 1/s synchronous discharges. This case illustrates for the first time that in panencephalopathic type of CJD the cerebral white matter can be involved primarily and more extensively than the gray matter. PMID- 2187698 TI - Deep cerebral venous system thrombosis in adults. AB - Two fatal cases of deep cerebral venous system thrombosis are reported in adults. The first case looked like a diencephalic tumor or encephalitis but the diagnosis was made antemortem by means of cerebral angiography. Autopsy found bilateral infarction of basal ganglia. The second patient presented with a hemorrhagic infarction of right thalamus and basal ganglia. Deep cerebral venous occlusion was diagnosed at autopsy. In spite of a few cases of survival, the thrombosis of the galenic system remains often fatal. The pathological changes and indications for anticoagulation are discussed. PMID- 2187699 TI - Transcranial Doppler sonography as a diagnostic tool in vascular dementia. AB - Transcranial Doppler monitoring of the flow velocity at the level of the middle cerebral artery was performed in 40 demented patients, 20 with multi-infarct dementia (MID) and 20 with senile dementia of the Alzheimer type (SDAT), and in 25 age-matched controls. The following conditions were evaluated: (1) rest; (2) 60 s hyperventilation; (3) longest possible apnea, and (4) 5 min closed-circuit air rebreathing. We also measured: PaCO2 levels at rest and under stimulus conditions; mean flow velocity and pulsatility index (PI) at rest, and percentage velocity variations. The PIs were higher and the velocity decrease during hyperventilation was lower in all demented patients than in the healthy group; no side-related asymmetry in rest values or in vasomotor responses to CO2 changes was regularly detected in any group. On the contrary, rest flow velocities and vasomotor responses to hypercapnia induced by both apnea and rebreathing tests proved to be lower in MID patients than in SDAT and healthy groups. These alterations were neither exclusive to MID patients nor homogeneous, therefore some caution should be taken when evaluating single cases. PMID- 2187700 TI - Double-blind placebo controlled clinical trial of almitrine bismesylate in patients with chronic respiratory insufficiency. AB - The efficacy and safety of almitrine bismesylate, a new respiratory stimulant, in patients with the hypoxaemic form of chronic respiratory insufficiency caused by chronic bronchitis and emphysema has been assessed. The multicentre trial of 12 weeks duration was double-blind and placebo controlled, with individual and group comparisons. Twenty three patients received almitrine 50 mg b.d. p.o. and 17 took placebo. In the almitrine group a significant increase in PaO2 was achieved (control value 54.4 mm Hg, rising to 59.1 mm Hg after 6 weeks, and to 59.4 mm Hg after 12 weeks). There was also a significant decrease in PaCO2 in the almitrine group after 12 weeks. No correlation was found between the plasma almitrine concentration, PaO2 and PaCO2. Lung function (FVC, FEV1, FEV1/FVC, Raw, TLC, RV, FRC) did not change in either group, but the degree of dyspnoea and performance in the 6 min walking test were significantly improved in the almitrine group. Adverse reactions appeared in 6 out of 23 patients on almitrine bismesylate (headache, urticaria, breathlessness, diarrhoea, chest pain, nausea and vomiting), causing drop out of 4 patients. Thus, almitrine bismesylate can be considered useful in the treatment of patients with chronic respiratory insufficiency. PMID- 2187701 TI - Comparison of the renal effects of dilevalol and carteolol in patients with mild to moderate essential hypertension. AB - The effects of 6 weeks of treatment with dilevalol 100 mg once daily, or carteolol 10 mg once daily, on renal blood flow (RBF), glomerular filtration rate (GFR) and total renal vascular resistance (TRR) were studied in 10 patients with mild-to-moderate essential hypertension in a randomised cross-over experiment. Both drugs lowered the systolic and diastolic blood pressures to a similar extent without altering the heart rate. Carteolol non-significantly decreased RBF by 9.2% and GFR by 12.3% without altering. TRR, whereas dilevalol produced a significant reduction in TRR by 13.2% (p less than 0.05), a non-significant decrease in RBF by 4.6% and no change in GFR. Neither drug changed plasma osmotic pressure, serum total protein concentration, electrolytes or plasma aldosterone concentration. Plasma renin activity tended to be lower in the dilevalol phase as compared to the carteolol phase. The results suggest that dilevalol may cause a greater decrease in TRR and less reduction in GFR when compared to carteolol in patients with mild-to-moderate essential hypertension. The difference in the renal effects might be due to the difference in the potency of vasodilatory properties of both drugs at the doses applied. PMID- 2187702 TI - Endothelin and sarafotoxin S6b have similar vasoconstrictor effects and postsynaptically mediated mechanisms. AB - In the isolated perfused mesenteric vascular bed, porcine endothelin (ET) and sarafotoxin S6b produced direct vasoconstriction and potentiated nerve stimulation-induced vasoconstriction. ET also enhanced the vasoconstrictor response to exogenous norepinephrine (NE). Basal or stimulated endogenous NE release was not affected either by ET or sarafotoxin S6b. Qualitatively similar responses to ET and sarafotoxin S6b were always observed, although, in many cases, the response to ET was greater and longer lasting than to sarafotoxin S6b. These results indicate that vasoconstrictor responses to ET or sarafotoxin S6b are mediated primarily by postsynaptic mechanisms. No initial vasodilator response to ET or sarafotoxin S6b was observed in this mesenteric vascular preparation. PMID- 2187703 TI - Effect of captopril on oxyphenbutazone and ethanol-induced gastric lesions in rats. AB - We studied the effect of the angiotensin converting enzyme inhibitor, captopril, on two models of gastric ulcers; oxyphenbutazone and ethanol-induced lesions. There was a significant protective effect against oxyphenbutazone-induced ulcers, which was prevented by prior administration of indomethacin. Captopril, however, failed to protect against ethanol-induced lesions. These findings are discussed in the light of captopril being a sulfhydryl compound with prostaglandin releasing activity. PMID- 2187704 TI - Muscarinic receptor subtypes in rat pancreatic islets: binding and functional studies. AB - Cholinergic agents are potent modulators of insulin release that act via muscarinic receptors. We now investigated the muscarinic receptor subtype present in rat pancreatic islets in binding and functional studies. Binding of 5 nM [3H]N methylscopolamine ([3H]NMS) was half maximal at 30 min. At 60 min, the maximal total binding was 1.29% and the non-specific binding (presence of 100 microM atropine) was 0.18% of the total radioactivity per 10 micrograms islet protein. Unlabelled atropine inhibited [3H]NMS binding with an IC50 of ca. 30 nM. The rank order of antagonist high-affinity binding was atropine greater than sila hexocyclium methyl sulfate (SiHC; M1 greater than M3 greater than M2) greater than pirenzepine (M1 greater than M2 approximately M3) = methoctramine (M2 greater than M1 greater than M3). The high-affinity Kds were 8.5, 56, 1300 and 1300 nM, respectively. The high affinity Kd of the muscarinic receptor agonist, arecaidine propargyl ester (APE), was 8.1 nM. The EC50 for the biological effects of APE on insulin and glucagon secretion was 3.2 and 2.3 nM. The rank order for the high-affinity biological effects of antagonists (inhibition of APE-mediated insulin/glucagon release) was almost the same as for binding. The data indicate that rat pancreatic islets contain neither an M1 subtype (high-affinity for pirenzepine) nor an M2 subtype (high-affinity for methoctramine) receptor. However, the data evidence an M3 receptor subtype, since SiHC in the absence of the M1 receptor subtype shows a relatively high affinity to the receptors in rat pancreatic islets. PMID- 2187706 TI - Acute bronchoconstriction is not a stimulus for sympatho-adrenal activation in asthmatic or healthy subjects. AB - Bronchoconstriction has been found to cause little sympathoadrenal activation in asthmatic patients. It has been questioned whether this is due to blunted sympatho-adrenal reactivity in asthmatics or if bronchoconstriction is a stimulus for sympatho-adrenal activation at all. We therefore compared sympatho-adrenal responses in eight asthmatic patients and 12 healthy subjects by measurements of plasma adrenaline and noradrenaline concentrations before, during and after methacholine-induced bronchoconstriction. Significant bronchoconstriction was obtained in eight of the healthy subjects and in all of the asthmatics. Considerably higher concentrations of methacholine were required to evoke bronchoconstriction in the healthy subjects but the relative magnitudes of bronchoconstriction were similar in the two groups: peak expiratory flow (PEF) decreased by approximately 24 and approximately 28% and specific airway conductance (sGaw) decreased by approximately 68 and approximately 70% in asthmatics and controls, respectively). Methacholine-induced bronchoconstriction did not alter plasma catecholamine levels significantly in either group. In addition, plasma concentrations of catecholamines and neuropeptide Y-like immunoreactivity (NPY-LI) were measured before and during bronchoconstriction induced by histamine or allergen in 8 and 5 asthmatic subjects, respectively. Plasma noradrenaline, adrenaline and NPY-LI remained unchanged up to 30 min after bronchoconstriction induced by histamine or allergen. We, therefore, conclude that bronchoconstriction is not a stimulus for sympatho-adrenal activation and that the lack of an adrenaline response to bronchoconstriction is not likely to be related to NPY release. PMID- 2187705 TI - Phagocyte enzymes in bronchoalveolar lavage from patients with pulmonary sarcoidosis and collagen vascular disorders. AB - The balance between proteases and antiproteases in the lower respiratory tract is believed to play a role in the outcome of interstitial lung diseases. In this cross-sectional study, we measure several phagocyte derived enzymes, namely plasminogen activator, neutrophil elastase and an ill-defined protease active on the trialanine chromophore substrate succinyl-alanine3-nitroanilide (SLAPN) in bronchoalveolar lavage (BAL) fluid from 42 patients with pulmonary sarcoidosis and from 43 patients with collagen vascular disease (CVD), 22 without lung disease (group I) and 21 associated with parenchymal lung disease (group II). The results show: a) that sarcoidosis is associated with increased plasminogen activator activity and with the presence of enzymatic activity against SLAPN corresponding at least in part to a metalloprotease; b) that CVD in the absence of radiographic lung disease is associated with an increase of plasminogen activator activity and increased levels of alpha 1-antiprotease-neutrophil elastase complexes; c) that the majority of untreated CVD (group II) patients have detectable levels of neutrophil elastase activity. These data show that patients with pulmonary sarcoidosis and CVD have different enzymatic profiles in their lower respiratory tract as assessed by BAL. Thus, sarcoidosis (mostly lymphocytic) is associated with enhanced macrophage-derived proteolytic activity in BAL, while CVD patients both with and without lung disease have increased neutrophil counts and neutrophil elastase complexed to alpha 1-protease inhibitor and presumably inactive in BAL. Finally, only BAL from untreated CVD patients with interstitial lung disease contain neutrophil elastase activity. This latter activity could contribute to the lung lesions frequently observed in these disorders. PMID- 2187707 TI - Endotoxin-induced plasma exudation in guinea-pig airways in vivo and the effect of neutrophil depletion. AB - The contribution of neutrophils to the action of endotoxin on plasma exudation in the airways of anaesthetized guinea-pigs was quantified by measuring the extravasation of Evans blue dye. Endotoxin (Salmonella enteritidis) caused a dose dependent increase in microvascular leakage to Evans blue dye which was maximal after 25 min (p less than 0.05). The minimum dose tested that induced a significant rise in leakage was 1.5 mg.kg-1 for "central" intrapulmonary airways (ipa); 4.5 mg.kg-1 for trachea and main bronchi and 7.5 mg.kg-1 for nasal mucosa, larynx and "peripheral" ipa. Depletion of circulating neutrophil numbers by 97% using an antibody to guinea-pig neutrophils caused no significant diminution of the effects of endotoxin on leakage in any part of the airway. There was no significant influx of neutrophils into the airway interstitium at the time of maximum extravasation of Evans blue. We conclude that endotoxin-induced airway microvascular permeability is dependent upon mechanisms other than circulating neutrophils. PMID- 2187708 TI - The role of increased airway microvascular permeability and plasma exudation in asthma. AB - Airway oedema and inflammation are recognized as cardinal features of asthma, resulting from increase microvascular permeability of the bronchial circulation with the exudation of plasma and inflammatory cells into the airway lumen. Resistance to airflow is increased and the epithelium is disrupted either directly or by cytotoxic proteins derived from migrating inflammatory cells. Such mediators include bradykinin, platelet-activating factor (PAF), leukotrienes and histamine. Antigen-induced and neurogenic inflammation, generated by immunoglobulin E (IgE) and neuropeptides respectively, may also contribute to oedema generation. Assessment of increased bronchial vascular permeability in animals has largely involved measurement of the extravasation of radiolabelled albumin or protein-bound dyes. Non-invasive techniques are less reliable in humans, but measurement of the rate of clearance of inhaled particles labelled with isotope may prove successful. Airway oedema appears to be an important feature of asthma and future research may be aimed at developing drugs that specifically prevent airway microvascular leakage. PMID- 2187709 TI - Bronchoalveolar lavage in allergic asthma. PMID- 2187710 TI - Role of bronchoalveolar lavage in the investigation of cell-mediated defence mechanisms against lung cancer. PMID- 2187711 TI - Lung defence mechanisms against infection. PMID- 2187712 TI - Role of bronchoalveolar lavage in the assessment of pulmonary complications following bone marrow and organ transplantation. PMID- 2187713 TI - [Mikhail Ivanovich Barsukov]. PMID- 2187714 TI - Stroke rehabilitation: a case presentation and review. PMID- 2187715 TI - Viral hepatitis: current status. PMID- 2187716 TI - Margaret Irving Handy: a lady and a doctor. PMID- 2187717 TI - Heat (shock) and the skin. AB - Whereas hyperthermia has long been used in dermatology for the therapy of diseases as diverse as syphilis, gonorrhea, psoriasis or melanoma, the understanding of the biological effects of heat shock on the skin attracts new interests to an old field. The proteins induced by heat (stress, or heat shock proteins) appear to play a general role in protection from cellular injury and eventually in the natural defences from solar radiation. On the other hand, these ubiquitous proteins may also be involved in the immunopathology of diseases such as systemic lupus erythematosus or leprosy. PMID- 2187718 TI - Frequency of congenital nevi, nevi spili and cafe-au-lait spots and their relation to nevus count and skin complexion in 939 children. AB - To determine the prevalence of congenital melanoevocytic nevi (CMN), of so-called congenital nevus-like nevi (CNLN), nevi spili (NS) and cafe-au-lait spots (CLS) in childhood, a series of 939 children aged 8-16 years had total skin examination. CMN/CNLN were observed in a frequency of 5.9%, NS in 2.1% and CLS even in 32.7%. Except CLS (which occurred more frequently in boys), all of these lesions were equally represented in both sexes. According to the classification of Kopf and coworkers, 44/55 CNM/CNLN were small and 11/55 medium-sized. CMN/CNLN affected preferentially trunk and upper limbs while head and neck were spared. Such nevi occurred more frequently in dark types of skin complexion and showed a tendency to be more frequent in groups of patients with increased average number of acquired melanonevocytic nevi. Remarkably, CLS were also found in 23/55 (41.7%) children with CMN/CNLN and in 12/20 (60%) children with NS (in a higher frequency than such combinations have to be expected). Compared with the data from other studies, both CMN/CNLN and CLS in our patients were observed in highest prevalence in the literature. Since the frequency of CLS in adults is much lower, it cannot be ruled out that some of the CLS disappear in adolescence. PMID- 2187719 TI - Management of nonstaphylococcal toxic epidermal necrolysis: follow-up study of 16 case histories. AB - In this study the clinical and laboratory data of 14 patients who experienced 16 attacks of nonstaphylococcal toxic epidermal necrolysis (TEN) are presented. All patients were treated in the Department of Dermatology of the University Hospital of Utrecht. Only 1 patient died. Attention is focused on a successful management consisting of reversed barrier nursing, painstakingly executed skin care, timely use of antibiotics and a therapy consisting of high dosages of corticosteroids. Thorough management in centers experienced in the treatment of TEN is essential for good treatment results. Further investigations concerning the use of corticosteroids in treating TEN are needed. PMID- 2187720 TI - Oral psoriasis: report of a case and review of the literature. AB - Psoriasis is a chronic inflammatory skin disease which very rarely affects the oral mucosa. In the present article, an interesting case of psoriasis with exclusive oral involvement is described. The patient's history, clinical, microscopic features, and HLA typing were consistent with a diagnosis of psoriasis. A review of the 68 reported cases of oral psoriasis is presented in table form. PMID- 2187721 TI - Familial lichen planus. AB - Familial lichen planus (FLP) was observed to have developed within a period of 3 years in 2 sisters as well as in the son of one of the women. In contrast to typical FLP, the eruption was generalized in only 1 of these patients; no atypical forms were observed; the response to topical treatment with steroids was rapid, and the relapses were few and mild. Previous reports of familial cases of lichen planus as well as the long interval between onset of the disease in the affected members of the family speak in favor of a genetic predisposition. HLA typing revealed HLA DR in all 3 patients. There was no increased incidence of HLA B7, HLA A3 or HLA A28. PMID- 2187722 TI - Lymphoplasmocytoid immunocytoma. PMID- 2187723 TI - A controlled trial of recombinant interferon-alpha in Caucasian children with chronic hepatitis B. AB - Twenty-four children with chronic active hepatitis due to hepatitis B virus (HBV) infection, who were positive for HBeAg and had increased levels of transaminases, were included in a controlled study of treatment using recombinant interferon alpha (rIFN-alpha), 10 MU/m2 body surface, intramuscularly, 3 times a week over a period of 3 months. During therapy, a significant decrease in HBV-DNAp was observed in the 12 patients treated. By the end of therapy, the HBV-DNA had disappeared in 3 children, the same occurring in 1 child (33% overall) during the course of the 4th month. By this time, all the controls remained with HBV replication markers (p less than 0.05). The 4 treated patients who responded became HBeAg-negative, developing anti-HBe during the first 12 months after therapy. In the control group, the HBV-DNA disappeared in 3 children in the 7th month of follow-up. All of the children remained HBsAg-positive. The therapy with rIFN-alpha was well tolerated, secondary effects consisting of a flu-like syndrome and a slight decrease in leukocytes and platelets. At the second biopsy, 15 months after the beginning of therapy, a significant decrease in Knodell's index of histological activity was observed in the responders. In the light of these results and since treated children lost viral replication markers in a shorter period of time than the controls, who seroconverted spontaneously, we consider that rIFN-alpha may be useful in the treatment of chronic hepatitis B in childhood. PMID- 2187724 TI - Otoacoustic emissions in human ears: normative findings. AB - Otoacoustic emissions can be separated into two interrelated classes according to the type of eliciting stimulus. On the basis of this categorization, four discrete subtypes can be recognized that include spontaneous, transiently evoked, stimulus-frequency, and distortion-product otoacoustic emissions. Methods of recording and findings in the ears of normally hearing humans are reviewed for each emission type. PMID- 2187725 TI - The clinical utility of distortion-product otoacoustic emissions. AB - Otoacoustic emissions permit, for the first time, an unbiased means of examining the preneural elements of the peripheral auditory pathway that make the initial contribution to the perception of acoustic stimuli. Distortion-product otoacoustic emissions (DPOAEs) represent one type of evoked emission that has significant potential for becoming an important test in the audiometric evaluation of hearing capacity. In the present review, selected examples of several forms of sensorineural hearing loss demonstrate that DPOAEs have the ability to act as objective indicators of the frequency/level configuration of the conventional audiogram in cases in which hearing impairment results primarily from damage to the outer hair cells. In contrast, normal DPOAE functioning, in the presence of a significant hearing loss, indicates a locus of damage central to the region of the outer hair cells. Like the other emitted responses, DPOAEs can be measured noninvasively, are highly repeatable, under test-retest conditions, and are simple and rapid to detect using microcomputer-based instrumentation. Further, DPOAEs test both the "threshold" and suprathreshold levels of outer hair-cell activity in the form of response/growth functions, over a 30- to 40-dB stimulus range. In combination, these attributes indicate that DPOAEs can provide an objective and comprehensive assessment of the cochlear reserve of a given ear. PMID- 2187726 TI - Clinical significance of otoacoustic emissions: a perspective. AB - The aim of this paper is to review the properties of otoacoustic emissions from a clinical point of view and to discuss the perspective interest of this test. In adults, the clinical significance of evoked otoacoustic emissions seems to be limited either in endocochlear hearing losses or for detecting retrocochlear diseases. In infants, evoked otoacoustic emissions seem to be a reliable, simple, non-invasive, and precise method for estimating auditory sensitivity for midfrequencies (1-4 kHz). Then, EOEs could be considered as an interesting way for screening auditory dysfunction in infants. PMID- 2187727 TI - Outer hair cell electromotility and otoacoustic emissions. AB - Outer hair cell electromotility is a rapid, force generating, length change in response to electrical stimulation. DC electrical pulses either elongate or shorten the cell and sinusoidal electrical stimulation results in mechanical oscillations at acoustic frequencies. The mechanism underlying outer hair cell electromotility is thought to be the origin of spontaneous otoacoustic emissions. The ability of the cell to change its length requires that it be mechanically flexible. At the same time the structural integrity of the organ of Corti requires that the cell possess considerable compressive rigidity along its major axis. Evolution appears to have arrived at novel solutions to the mechanical requirements imposed on the outer hair cell. Segregation of cytoskeletal elements in specific intracellular domains facilitates the rapid movements. Compressive strength is provided by a unique hydraulic skeleton in which a positive hydrostatic pressure in the cytoplasm stabilizes a flexible elastic cortex with circumferential tensile strength. Cell turgor is required in order that the pressure gradients associated with the electromotile response can be communicated to the ends of the cell. A loss in turgor leads to loss of outer hair cell electromotility. Concentrations of salicylate equivalent to those that abolish spontaneous otoacoustic emissions in patients weaken the outer hair cell's hydraulic skeleton. There is a significant diminution in the electromotile response associated with the loss in cell turgor. Aspirin's effect on outer hair cell electromotility attests to the role of the outer hair cell in generating otoacoustic emissions and demonstrates how their physiology can influence the propagation of otoacoustic emissions. PMID- 2187728 TI - Developmental expression of adenosine deaminase in the upper alimentary tract of mice. AB - The distribution and localization of adenosine deaminase (ADA) was studied during postnatal development of the alimentary tract in mice. There was detectable enzyme activity in all organs examined, but a range of more than 10,000 fold in the relative levels of specific activity was observed among adult tissues. A comprehensive survey of multiple adult tissues revealed that the highest levels of ADA occur in the upper alimentary tract (tongue, esophagus, forestomach, proximal small intestine). Immunohistochemical analysis revealed that ADA was predominantly localized to the epithelial lining of the alimentary mucosa: the keratinized squamous epithelium that lines the forestomach, esophagus, and surface of the tongue; and the simple columnar epithelium of the proximal small intestine (duodenum, proximal jejunum). Biochemical analysis revealed that ADA was one of the most abundant proteins of these mucosal tissue layers, accounting for 5%-20% of the total soluble protein. Tissue-specific differences in ADA activity correlated both with levels of immunoreactive protein and RNA abundance. The level of ADA activity in the upper alimentary tissues was subject to pronounced developmental control, being low at birth and achieving very high levels within the first few weeks of postnatal life. The appearance in development of ADA-immunoreactivity coincided with maturation of the mucosal epithelium. These results suggest that ADA is subject to strong cell-specific developmental regulation during functional differentiation of certain foregut derivatives in mice. PMID- 2187729 TI - Ultrasonic features of duodenal ulcer. AB - Five cases of duodenal peptic ulcers studied by ultrasound are presented. In all 5 patients, a hyperechoic area in various shapes and sizes corresponding to ulcers in x-ray was identified adjacent to gallbladder and head of the pancreas. This hyperechoic center was surrounded by a hypoechoic halo in various thicknesses representing duodenal wall edema and infiltration. While not recommending ultrasonography in the detection of ulcer disease, the ultrasonographic pattern of an ulcer should be recognized so that when it is seen, an upper gastrointestinal series can be performed as the next diagnostic study. PMID- 2187730 TI - Comparison between ultrasonographic signs and the degree of portal hypertension in patients with cirrhosis. AB - The sensitivity of ultrasonography (US) for the diagnosis of portal hypertension was assessed in 48 patients with known cirrhosis. These results were compared to the hemodynamic values obtained on the same day by hepatic vein catheterization. The sensitivity of US in detecting portal hypertension was about 40% considering either a greater than 13 mm diameter of the portal vein, or the lack of mild caliber variation of the superior mesenteric vein. The sensitivity was more than 80% considering the presence of portosystemic venous collaterals. Presence of numerous portosystemic shunts was significantly associated with high hepatic venous pressure gradients which reflected the severity of portal hypertension. PMID- 2187731 TI - Acoustic artifacts and reverberation shadows in gallbladder sonograms: their cause and clinical implications. AB - From among more than 7000 sonographic examinations of the gallbladder performed over a period of 2 years, different types of acoustic artifacts were observed in 42 patients. Artifacts originated in the gallbladder wall in 37 cases and within the lumen in 5 cases. Eighteen patients had symptoms related to the hepatobiliary area. Twenty-four patients were fully asymptomatic although cholelithiasis was demonstrated in 8. In 21 cases (50%) some type of gallbladder pathology was associated with the presence of acoustic artifacts. Thirteen patients were cholecystectomized and the associated gallbladder pathology consisted of cholelithiasis (N = 5), cholesterolosis (N = 2), adenomyomatosis (N = 2), emphysematous cholecystitis (N = 2), and acute cholecystitis (N = 2). In 3 of these patients a sonographic/pathologic correlation was established. Only 5 of the 18 symptomatic patients presented acoustic artifacts in an otherwise normal gallbladder. Recognition of those pathological conditions favorable to the appearance of artifacts and reverberation shadows is extremely useful for differentiating merely clinically irrelevant anomalies from those that require prompt management. PMID- 2187732 TI - Ultrasonically guided percutaneous drainage of abdominal fluid collections: a long-term study of its therapeutic efficacy. AB - Fifty patients underwent ultrasonically guided percutaneous drainage (US-GPD) either with needle aspiration or catheter drainage. The procedures resulted in 70% complete recovery, 20% partial success and 10% of failures. The same patients were followed with clinical examination and sonography for a mean time of 36.3 months (minimum follow-up: 12 months). During the follow up period, 10 relapses occurred and one patient, considered for surgery after partial percutaneous treatment of a pyogenic liver abscess, recovered completely under conservative treatment. An analysis of the factors potentially related to the recurrence was made. It was found that one-step needle aspiration of abdominal abscesses and percutaneous treatment of chronic pancreatic pseudocysts are more prone to relapses. We conclude that US-GPD is an efficacious therapy for abdominal fluid collections, but an adequate drainage technique and a careful selection of the patients is crucial to avoid the possibility of relapse. PMID- 2187733 TI - [The status of prenatal lung ripening]. AB - Morbidity and mortality of low-weight infants depend mainly on the respiratory distress syndrome (RDS) and its complications, such as neonatal asphyxia and intraventricular haemorrhage. This underlines the importance of prenatal prevention of RDS. The results of the present multicentre studies demonstrate successful acceleration of fetal lung maturation by glucocorticoids and ambroxol. Both agents lower the RDS-rate two to threefold. The effectiveness in accelerating fetal lung maturation is comparable. In contrast to glucocorticoids, ambroxol seems to have no severe potential maternal or fetal side effects. We believe that prenatal prevention of RDS remains the treatment of choice even if neonatal surfactant therapy is expected to open up new aspects for the future. PMID- 2187734 TI - [Abruptio placentae]. AB - Neither the frequency nor the clinical pattern of abruptio placentae have changed significantly in the past years. In a retrospective study (1979-1988) we found a frequency of 0.55%, that means one abruptio placentae in every 182 births. Important and significant factors which could be correlated with the abruptio placentae were: premature labour, vaginal bleeding and gestosis. The case histories show a high rate of abortions and interruptions (24.3%) of pregnancy, as well as premature rupture of membranes (15.4%) and multiple pregnancies. Ultrasound furnished valuable diagnostic criteria in only 7.7% of the cases. A high rate of breech presentation (1/5 of all cases) is seen in combination with premature birth (37% less than or equal to 33 weeks of gestation). Half of the patients showed disturbances of coagulation. The high rate of perinatal mortality (12%) is related to the prematurity on the one hand and too late diagnosis of abruptio placentae. PMID- 2187735 TI - [Prenatal use of pulsed Doppler ultrasound within the scope of the differential diagnosis of bilateral kidney abnormalities]. AB - Pulsed Doppler ultrasound was used in the differential diagnosis of 22 cases suspected of bilateral malformations of the foetal kidneys. In cases of kidney malformations, the pulsatility indices (PI) of the umbilical artery and the foetal aorta were in the normal range. In cases showing pathological PI values of both vessels, we found a severe intrauterine growth (IUGR) retardation with oligohydramnion. These results underline the importance of pulsed Doppler as a non invasive means in the management of oligohydramnions to differentiate among bilateral kidney malformations and IUGR. PMID- 2187736 TI - The genetics of human alcohol metabolism. AB - 1. The custom of drinking alcoholic beverages is a human behavior with serious social and medical consequences for a surprisingly large fraction of drinkers. 2. This review describes recent advances in our understanding of the genetic loci that control enzyme systems involved in the metabolism of alcohol. 3. These advances make possible new experimental programs that may lead to simple diagnostic tests for patients at risk of developing alcohol abuse behaviour. PMID- 2187737 TI - Structure and hypotensive activity relationships of tetrandrine derivatives in stroke-prone spontaneously hypertensive rats. AB - 1. Structure and hypotensive activity relationships of tetrandrine (TD), an alkaloid isolated from the Chinese herb Radix stephaniae tetrandrae and its derivatives were investigated in conscious stroke-prone spontaneously hypertensive rats (SHRSP). 2. Derivatives substituted at the 7-O position with various types of alkyl group produced varying degrees of hypotensive effect. 3. While the demethylated derivative, fangchinoline (FC), and its acetylated compound had no effect on blood pressure, 7-O-methyl FC (TD), and 7-O-ethyl and 7 O-isopropyl FC at oral doses of 25 and 50 mg/kg produced a gradual and sustained hypotensive effect without any significant effects on heart rate and plasma renin concentration. 4. Substitution at the 7-O position with longer side chains such as n-propyl, n-butyl and n-pentyl groups reduced both the degree and duration of hypotensive activity. 5. Substitution of N-methyl groups at the 2 and 2' positions with quaternary ammonium or N-oxide attenuated the hypotensive activity. 6. The results of this study suggest a possibility that 7-O-ethyl and 7 O-isopropyl derivatives as well as TD can be considered as potential antihypertensive drugs because of the gradual onset and long duration of their hypotensive action in SHRSP. PMID- 2187738 TI - Transcriptional control of SSL1, a gene controlling alpha-specific inactivation of a-factor in Saccharomyces cerevisiae. AB - The SSL1 gene of S. cerevisiae which is involved in the cell-type specific recovery of mating type alpha cells from cell cycle arrest by the mating hormone a-factor has been cloned as a 1 kb Sau3A fragment in a complementing plasmid from a library of S. cerevisae genomic DNA. Disruption of this gene in wild-type alpha cells results in the ssl1- phenotype which is characterized by an extreme sensitivity to a-factor. Transcription analysis revealed that the SSL1 gene is transcribed only in MAT alpha cells but not in MAT alpha or diploid (MAT alpha/MAT alpha) cells defining it as a member of the set of alpha-specific genes. PMID- 2187739 TI - Use of the polymerase chain reaction to detect DNA sequences specific to pathogenic treponemes in cerebrospinal fluid. AB - The polymerase chain reaction was used to detect Treponema pallidum in specimens of cerebrospinal fluid (CSF), as a means of diagnosing syphilis. Segments of the TmpA and 4D genes were amplified to provide an estimated threshold sensitivity of approximately 65 organisms in 0.5 ml. A spectrum of pathogens known to cause meningitis, and several non-pathogenic treponemes were unreactive. Treponema pertenue, and only one of 30 control specimens of CSF were positive. In contrast, 10 of 19 CSFs from patients being evaluated for latent or tertiary syphilis were positive, as were 7 of 28 specimens from HIV-positive patients. PMID- 2187740 TI - Adherence of Candida albicans to components of the subendothelial extracellular matrix. AB - Candida albicans yeasts adhered avidly to extracellular matrix (ECM) proteins, type IV collagen, laminin, and fibronectin immobilized on plastic. Type IV collagen showed an increase of adherence of 400% above control values; laminin, 300%; and fibronectin, 150%. In addition, all three (in quantities of 0.02-200 micrograms/well of a culture tray) bound yeasts in a dose-response fashion. Adherence was inhibited when the proteins were preincubated with specific antibody, except with type IV collagen. Soluble laminin or fibronectin inhibited yeast adherence to the same proteins by 36 and 94%, respectively. Soluble fibronectin bound to the yeast surface and in so doing inhibited subsequent yeast adherence to fibronectin by 66%. By comparison, Candida albicans yeasts adhered in smaller numbers to glycosaminoglycans (GAGs). Keratan sulfate, hyaluronic acid, chondroitin sulfate, Type B, and heparin actually decreased yeast adherence compared to control from 10% to 25%. PMID- 2187741 TI - A single protein of 110 kDa is associated with the multinucleating and necrotizing activity coded by the Vir plasmid of Escherichia coli. AB - A lethal and necrotic factor which causes cell multinucleation in HeLa cell cultures has previously been shown to be coded by the Vir plasmid of Escherichia coli. Using an absorbed rabbit antiserum which neutralized the Vir toxic properties, we have compared the SDS-PAGE immunoblots from laboratory and field strains which either produce or do not produce Vir toxicity. A single band of 110 kDa was found to be specifically associated with vir toxicity in E. coli strains. This antiserum also recognized the 115 kDa protein band which was previously identified as the cytotoxic necretozing factor (CNF) of certain E. coli strains. These results suggest that the toxin coded by the Vir plasmid is a protein of 110 kDa distinct from, but immunologically related to CNF. PMID- 2187742 TI - Alan Robertson (1920-1989). PMID- 2187743 TI - GAL4 mutations that separate the transcriptional activation and GAL80-interactive functions of the yeast GAL4 protein. AB - The carboxy-terminal 28 amino acids of the Saccharomyces cerevisiae transcriptional activator protein GAL4 execute two functions--transcriptional activation and interaction with the negative regulatory protein, GAL80. Here we demonstrate that these two functions are separable by single amino acid changes within this region. We determined the sequences of four GAL4C-mutations, and characterized the abilities of the encoded GAL4C proteins to activate transcription of the galactose/melibiose regulon in the presence of GAL80 and superrepressible GAL80S alleles. One of the GAL4C mutations can be compensated by a specific GAL80S mutation, resulting in a wild-type phenotype. These results support the idea that while the GAL4 activation function tolerates at least minor alterations in the GAL4 carboxyl terminus, the GAL80-interactive function is highly sequence-specific and sensitive even to single amino acid alterations. They also argue that the GAL80S mutations affect the affinity of GAL80 for GAL4, and not the ability of GAL80 to bind inducer. PMID- 2187745 TI - Complete sequence of the ompH gene encoding the 16-kDa cationic outer membrane protein of Salmonella typhimurium. AB - The complete nucleotide sequence of the ompH gene encoding the 16-kDa basic outer membrane protein of Salmonella typhimurium was determined. The OmpH protein is synthesized in a precursor form with additional 20 amino acid residues in the N terminus of the protein. This peptide has common characteristics of signal sequences. The promoter region has strong homology to consensus sequences of Escherichia coli. The expression of ompH was detected in minicells. PMID- 2187744 TI - Construction of an efficient overproducer clone of HinfI restriction endonuclease using the polymerase chain reaction. AB - We describe the use of the polymerase chain reaction (PCR) technique to alter transcriptional and translational signals surrounding a gene so as to achieve overexpression in Escherichia coli. By changing the ribosome-binding site sequence preceding the hinfIR gene to match the consensus E. coli signal and by adding a transcription terminator sequence immediately following the gene, the yield of HinfI was increased about tenfold over that obtained from the natural Haemophilus influenzae signals. The addition of the positive retroregulator stem loop sequence derived from the crystal protein-encoding gene of Bacillus thuringiensis downstream from the hinfIR gene further increased yields by twofold to a level of 13% of the total cellular protein. PMID- 2187746 TI - TGATG vector: a new expression system for cloned foreign genes in Escherichia coli cells. AB - A TGATG vector system was developed that allows for the construction of hybrid operons with partially overlapping genes, employing the effects of translational coupling to optimize expression of cloned cistrons in Escherichia coli. In this vector system (plasmid pPR-TGATG-1), the coding region of a foreign gene is attached to the ATG codon situated on the vector, to form the hybrid operon transcribed from the phage lambda PR promoter. The cloned gene is the distal cistron of this hybrid operon ('overlappon'). The efficiently translated cro' cat'-'trpE hybrid cistron is proximal to the promoter. The coding region of this artificial fused cistron [the length of the corresponding open reading frame is about 120 amino acids (aa)] includes the following: the N-terminal portions of phage lambda Cro protein (20 aa), the CAT protein of E. coli (72 aa) and 3' C terminal codons of the E. coli trpE gene product. At the 3'-end of the cro'-cat' 'trpE fused cistron there is a region for efficient translation reinitiation: a Shine-Dalgarno sequence of the E. coli trpD gene and the overlapping stop and start codons (TGATG). In this sequence, the last G is the first nucleotide of the unique SacI-recognition site (GAGCT decreases C) and so integration of the structural part of the foreign gene into the vector plasmid may be performed using blunt-end DNA linking after the treatment of pPR-TGATG-1 with SacI and E. coli DNA polymerase I or its Klenow fragment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2187748 TI - Heat-labile phosphatase simplifies the preparation of dephosphorylated vector DNA. AB - A novel enzyme for DNA dephosphorylation, HK phosphatase, is completely and irreversibly inactivated at 65 degrees C. HK phosphatase treatment of BamHI digested pBR322 reduces nonrecombinants in cloning experiments to approx. 5% of transformant colonies. PMID- 2187747 TI - Stable expression of foreign antigens from the chromosome of Salmonella typhimurium vaccine strains. AB - A simple and versatile system has been developed using a new cloning vector which can serve as a vehicle for integrating DNA fragments, which direct the expression of heterologous antigens, into the aroC gene on the Salmonella chromosome. The system is based on Escherichia coli plasmid vectors which contain the DNA fragment, cloned from the chromosome of S. typhimurium C5, which encodes the aroC gene. The aroC gene was modified using synthetic oligodeoxyribonucleotides so that it contained several unique restriction sites into which DNA, directing the expression of heterologous antigens, could be cloned. DNA was integrated into the S. typhimurium chromosome at aroC by transferring the vectors into S. typhimurium polA mutants and allowing homologous recombination to occur between the cloned and chromosomal aroC genes. The vectors were used to integrate nucleotide sequences into the S. typhimurium chromosome which directed the expression of tetanus toxin fragment C and the Treponema pallidum lipoprotein. The expression of both antigens was detected by Western blotting. PMID- 2187749 TI - Leg ulcers: differential diagnosis in the elderly. AB - Leg ulcers are a common problem encountered in the elderly. Because their origins are often multifactorial, it is essential for the primary care physician to have a sound knowledge of differential diagnosis to institute proper treatment. This review discusses salient historical points as well as bedside physical examination techniques useful in patients presenting with leg ulcer. Also discussed are pathophysiology of most common types of ulcer, including venous disease, arterial disease, diabetes, and physical agents. Less common causes of leg ulcer are also reviewed. PMID- 2187750 TI - Identifying and managing stress incontinence in the elderly. AB - Stress incontinence is common in elderly women, as it is in childbearing and perimenopausal women, but it often presents differently and has different causes. Surgical repair remains the most effective therapy, but no one procedure will resolve all cases and sometimes other forms of therapy are preferable. The physician is urged to remain alert for signs and symptoms, to pursue the diagnosis, and to make informed referrals for care. PMID- 2187751 TI - Malignant melanoma: management guidelines. AB - The incidence of primary melanoma of the skin, once rare, has been increasing rapidly over the past few decades. Although it accounts for only 3% of all primary cutaneous malignancies, melanomas are responsible for two thirds of skin cancer-related deaths. Fortunately, early detection and surgical removal have resulted in a concomitant improvement in overall survival. Ongoing clinical trials are addressing various therapeutic alternatives, as well as whether any treatment modality will significantly increase response rates and survival in patients with advanced disease. These prospects are discussed, and current prognostic factors and available therapies reviewed. PMID- 2187752 TI - How "grass roots" physicians would modify Medicare. PMID- 2187753 TI - Perspectives in radioimmunoglobulin therapy. PMID- 2187754 TI - Dosimetry of heterogeneous uptake of radiolabeled antibody for radioimmunotherapy. PMID- 2187755 TI - Clinical experience of iodine-131 monoclonal antibodies in treating neural tumours. PMID- 2187756 TI - The earliest concept of the 'hybridoma principle' recognized in 1967-1968. PMID- 2187757 TI - Specific targeting of cancer with monoclonal antibodies. Diagnostic and therapeutic applications. PMID- 2187758 TI - High-dose radioimmunotherapy of B cell lymphomas. PMID- 2187759 TI - Treatment of gastrointestinal cancer using monoclonal antibodies. PMID- 2187760 TI - Radiolabeled monoclonal antibodies for the diagnosis and treatment of ovarian carcinoma. PMID- 2187761 TI - Organization of a monoclonal antibody clinical unit. PMID- 2187762 TI - The present and future role of monoclonal antibodies in the management of cancer. Summary. PMID- 2187763 TI - Tumor physiology and antibody delivery. PMID- 2187764 TI - Modulators of tumor responsiveness to radioimmunotherapy. PMID- 2187765 TI - Cancer imaging with radiolabeled antibodies. PMID- 2187766 TI - The physiological role of zinc as an antioxidant. AB - The purpose of this review is to consider whether an essential biochemical function of zinc (Zn) is to serve as an antioxidant. Zn has been shown to have an antioxidant role(s) in defined chemical systems. Two mechanisms have been elucidated; the protection of sulfhydryl groups against oxidation and the inhibition of the production of reactive oxygens by transition metals. Supraphysiological concentrations of Zn have antioxidant-like effects in organelle-based systems and isolated cell-based systems in vitro. Administration of pharmacological doses of Zn in vivo has a protective effect against general and liver-specific prooxidants. Dietary Zn deficiency causes increased susceptibility to oxidative damage in membrane fractions from some tissues suggesting that increased oxidative stress may be a small but significant component of the pathology observed in dietary Zn deficiency. However, the biochemical basis for Zn deficiency pathology remains unelucidated; critical antioxidant functions for Zn may still be uncovered. PMID- 2187767 TI - Oxidative muscular injury and its relevance to hyperthyroidism. AB - In experimental hyperthyroidism, acceleration of lipid peroxidation occurs in heart and slow-oxidative muscles, suggesting the contribution of reactive oxygen species to the muscular injury caused by thyroid hormones. This article reviews various models of oxidative muscular injury and considers the relevance of the accompanying metabolic derangements to thyrotoxic myopathy and cardiomyopathy, which are the major complications of hyperthyroidism. The muscular injury models in which reactive oxygen species are supposed to play a role are ischemia/reperfusion syndrome, exercise-induced myopathy, heart and skeletal muscle diseases related to the nutritional deficiency of selenium and vitamin E and related disorders, and genetic muscular dystrophies. These models provide evidence that mitochondrial function and the glutathione-dependent antioxidant system are important for the maintenance of the structural and functional integrity of muscular tissues. Thyroid hormones have a profound effect on mitochondrial oxidative activity, synthesis and degradation of proteins and vitamin E, the sensitivity of the tissues to catecholamine, the differentiation of muscle fibers, and the levels of antioxidant enzymes. The large volume of circumstantial evidence presented here indicates that hyperthyroid muscular tissues undergo several biochemical changes that predispose them to free radical mediated injury. PMID- 2187768 TI - [Sea sickness: a review of etiology, pathophysiology, evaluation and treatment]. PMID- 2187769 TI - [Habitual spontaneous abortions and the antiphospholipid autoantibody syndrome]. PMID- 2187770 TI - [Ovarian cancer--progress and stagnation]. PMID- 2187771 TI - [Cholesterol metabolism and atherosclerosis]. PMID- 2187772 TI - [Celiac disease where to? An update]. PMID- 2187773 TI - [Localized scleroderma]. PMID- 2187774 TI - [A search for an autoimmune immunoglobulin gene]. PMID- 2187775 TI - Evaluation of olestra in short-term genotoxicity assays. AB - Olestra, a mixture of hexa-, hepta- and octa-esters formed from the reaction of sucrose with long-chain fatty acids, was evaluated for its genotoxic potential in the Salmonella/mammalian microsome test, the L5178Y thymidine kinase (TK+/-) mouse lymphoma assay, an unscheduled DNA synthesis assay in primary rat hepatocytes, and an in vitro cytogenetic assay in Chinese hamster ovary cells. The results indicated that olestra was non-genotoxic in these assays. PMID- 2187776 TI - Complications of ankle arthroscopy. AB - Of over 4500 ankle arthroscopies recently surveyed by the Arthroscopy Association of North America, only one complication (an infection) was reported. Nerve injury, vascular injury, or reflex sympathetic dystrophy were not reported. The ankle's anatomy is complex and there are many structures that can be damaged by imprecise portal placement. A review of our experience with 53 consecutive ankle arthroscopies found nine complications for a rate of 17%. There were three permanent dorsal sensory nerve injuries, two synovial fistulas, three wound infections, and one reflex sympathetic dystrophy. A literature review found other reported complications to include instrument breakage, synovitis, painful scars and nodules, and fibula fracture. Complications occur with ankle arthroscopy more frequently than previously reported, and the average or beginning ankle arthroscopist should expect a higher rate of surgical complication than has been previously reported. PMID- 2187777 TI - [Lyme borreliosis. The manifestations of the disease from the internal medicine and rheumatology viewpoints]. AB - Lyme disease is an infectious syndrome transmitted by tick bites. Of the multiple manifestations, cardiac and joint involvement are of primary interest for internists and rheumatologists. Up to 10% of patients develop cardiac symptoms, most frequently a disturbance of atrioventricular conduction. The characteristic presentation of the disease, however, are of symptoms of arthritis in one or several large joints. This review summarizes Lyme disease with emphasis on presenting symptoms important to internists and rheumatologists. PMID- 2187778 TI - [Lyme borreliosis in neurology and psychiatry]. AB - Neurological manifestations of Lyme disease are as multifarious as the entire spectrum of this common infection. In stage I, fibromyalgia and, more rarely, painful muscular fasciculation, dominate the clinical picture. In the individual case, mild psychic abnormalities may already be observed. Characteristic of the 2nd stage is lymphocytic meningopolyneuritis. Involvements of the CNS are expressed not so much in focal deficits, as in diffuse psychopathological disorders. In stage 3, CNS manifestations are characterized by chronic, in part multifocal, encephalitides and encephalomyelitides, isolated transverse myelitides and cerebral vasculitic disorders. The clinical symptomatology may be dominated by severe psychiatric syndromes. Connatal and subclinical latent infections of the nervous system with Borrelia represent special forms. PMID- 2187779 TI - [The laboratory diagnosis of Borrelia burgdorferi infection]. AB - The multiplicity of the clinical appearance of Lyme disease makes it necessary to confirm the diagnosis by detecting the pathogen or specific antibodies. Isolation of the pathogen from infected tissue or body fluids is difficult, so that, to date, only serology is feasible for routine diagnosis. In view of a lack of standardisation of borrelia serology, the clinician must expect false negative, and--even more so--false-positive, results. Future laboratory diagnosis should be markedly improved by nucleic acid hybridisation for the detection of the pathogen, and the use of specific immunodominant antigens for antibody detection. PMID- 2187780 TI - [The clinical importance of magnesium. 2. The indications for supplementation and therapy]. AB - Mg deficiency is characterized by diverse secondary electrolyte alterations. Extracellularly, hypocalcemia is a particular feature, which may be explained by increased resistance of bone towards parathormone. Intracellularly, decreased concentrations of Mg and K and increased amounts of Na and Ca are found in contractile organelles. At increased Mg levels, concentration of parathormone may decrease, leading to hypocalcemia. Calcium-antagonistic effects are observed in smooth muscle, the myocardium and the end-plate of skeletal muscles. Hence, Mg may be prescribed either to correct a deficit or to utilize its pharmacologic effects. Dosaging still needs to be optimized. PMID- 2187781 TI - [Circumscribed indications for magnesium in cardiology]. PMID- 2187782 TI - [Treatment with nootropic drugs]. AB - The effectiveness of nootropic agents (cerebroactive substances) is still under controversial discussion. Confusion occurs owing to the fact that effectiveness tests are undertaken on quite different levels ranging from in vitro assays to observations of day-to-day living. Methods of testing the effectiveness of cerebroactive substances are presented, with consideration being given to the recommendations of the experts. PMID- 2187783 TI - [Multi-morbidity and pharmacotherapy in the aged. Considerations for the treatment of cerebral performance deficits]. PMID- 2187784 TI - Is it possible to predict the activity of a new antidepressant in animals with simple psychopharmacological tests? AB - Behavioural tests for predicting antidepressant activity in the animal provide a closer approximation than other tests of states of depression in man but are often long and costly to perform (except the behavioural despair test). The tests proposed here presuppose a pharmacological interaction (except the Porsolt test) but are simple enough to allow screening: included are antagonism of reserpine hypothermia, ptosis and akinesia; antagonism of effects induced by oxotremorine; antagonism of high-dose apomorphine; and potentiation of yohimbine toxicity. In combination with the study of motor activity in the mouse, these tests allow assessment of the specificity of antidepressant activity by establishing a ratio between the "antidepressant" dose and the "stimulant" or "sedative" dose. It can be predicted that a substance will be antidepressant and sedative or stimulant at the same dose if the ratio is close to 1; if the ratio is less than 1, at antidepressant doses the substance will be very sedative or stimulant according to the case. The specificity of the tests discussed can be debatable. Antagonism of reserpine-induced hypothermia indicates substances with direct or indirect beta-mimetic activity, ptosis antagonism, substances with alpha-adrenergic (not antidepressants) or serotoninergic (possibly antidepressants) activity; and akinesia antagonism, a direct or indirect dopaminergic activity (sometimes found in antidepressants) with psychostimulant activity. The oxotremorine test is related to the anticholinergic activity of substances, except in the case of hypothermia antagonism. The high-dose apomorphine test seems to be specific for substances inhibiting norepinephrine reuptake. The yohimbine test is simple to carry out, relatively inexpensive and does not fail to screen any molecule known to be effective to-date. The behavioural despair test is a good complement for screening except for drugs having a beta-agonist activity, it appears that this test is dependent on functional relationships between alpha 2 and serotonergic systems. PMID- 2187785 TI - Oxygen-derived free radicals and postischemic myocardial reperfusion: therapeutic implications. AB - Oxygen-derived free radicals have been implicated in the pathogenesis of various disease states, including myocardial ischemia and reperfusion. In this article, we review 1) the evidence linking free radical production and myocardial injury during myocardial ischemia and reperfusion and 2) results of studies of the effects of the pharmacological therapies available potentially to prevent free radical-mediated injury. Free radicals can be produced during ischemia and reperfusion by several different biochemical pathways. Of these, the xanthine oxidase reaction and the output of free radicals by neutrophils that have accumulated in damaged tissue have been studied extensively. When produced, free radicals can potentially damage myocytes or endothelial cells through peroxidation of membrane lipids or damage to proteins or nucleic acids. Using electron spin resonance spectroscopy, several studies have shown a 'burst' of oxygen free radicals immediately after reperfusion. Moreover, exogenous generation of intravascular free radicals has been shown to produce marked vascular and myocyte damage, as well as contractile dysfunction. 'Anti-free radical' interventions, such as xanthine oxidase inhibitors and free radical scavengers have been reported to prevent contractile dysfunction and reperfusion induced arrhythmias after an episode of reversible ischemic injury. However, after more severe episodes of ischemia, such interventions have had conflicting effects on myocardial infarct size. 'Anti-free radical' interventions could be of potential use in situations where reversible ischemic injury occurs. In situations where reperfusion is achieved after irreversible ischemic injury has occurred, the potential beneficial effect of these treatments on infarct size is more doubtful. PMID- 2187786 TI - Activated Kupffer cells as a factor of massive hepatic necrosis after liver resection. PMID- 2187787 TI - Classification of gastric carcinoma. AB - In this review the main classification systems of gastric carcinomas are described. Besides topographical aspects, the macroscopic features of early and advanced gastric cancers are summarized. Also scanning microscopic typings, the WHO typing, and various histogenetic classifications are reviewed. The main prognostic categorizations, like the TNM classification of the UICC and the Japanese classification of lymph nodes, are described, together with their prognostic significance. Finally, the special significance of the R classification is stressed. PMID- 2187788 TI - First randomized controlled trial with sucralfate versus H2-antagonists in the treatment of duodenal ulcer non-responders to initial treatment with sucralfate. PMID- 2187790 TI - HCFA targets group retirees for managed care. PMID- 2187789 TI - Expanded delivery system needed for post-traumatic stress. AB - For many Vietnam combat veterans, the war never ended. They fight it over and over again in their minds. Their condition is called post-traumatic stress disorder. The Department of Veterans Affairs has made significant strides in treating these vets, but the VA is able to meet only a small part of the veterans' demand for treatment. A need exists at the community level, particularly in rural areas, where many veterans do not have access to the specialized treatment they need without traveling great distances and navigating red tape. PMID- 2187791 TI - Sulphaphenazole, streptomycin and sulphaphenazole combination, trimethoprim, and erythromycin in the treatment of chancroid. AB - One hundred and thirty six patients with chancroid were treated with four different treatment regimens; (A) Sulphaphenazole 1 g 12 hourly by mouth x 10 days (B) Inj streptomycin 1 g intramuscularly daily with sulphaphenazole 1 g 12 hourly orally x 10 days; (C) trimethoprim 200 mg 12 hourly by mouth x 7-10 days, and (D) erythromycin 500 mg 6 hourly orally x 7-10 days. Cure rates of 9% with sulphaphenazole alone, 48% with streptomycin and sulphaphenazole combination, 93% with trimethoprim and 100% with erythromycin were obtained. Sulphaphenazole alone or in combination with streptomycin were thus inferior in the treatment of chancroid. There is need for modification of treatment regimens recommended for chancroid in the textbooks of dermatology and venereology. Trimethoprim can be recommended as first line of treatment for chancroid in developing countries like India where resistance to trimethoprim is uncommon and erythromycin is suggested as a second line of therapy because by that time syphilis can be easily ruled out. PMID- 2187792 TI - Syphilis in art: an entertainment in four parts. Part 2. PMID- 2187793 TI - Syphilis, gonorrhoea and genital chlamydial infection in a Somali village. AB - A total of 767 sera were collected from 187 men, 200 women and 380 children in a Somali village, Jambaluul. All sera were tested for syphilis serological markers by Venereal Diseases Research Laboratory (VDRL) and Treponema pallidum Haemagglutination Assay (TPHA). Sera positive for both or either of these tests were further analysed for the presence of specific IgM antibodies by Solid Phase Haemadsorption Assay (SPHA). A high and almost equal prevalence of TPHA positivity was found in men and women; 24% and 22.5%, respectively, and IgM antibodies were found in 3% and 4%, respectively. TPHA positivity significantly increased with age. Thus more than half of the villagers at the age of 45 years or more were TPHA positive. One percent of the children were TPHA positive. From all adults aged 15 years and above urogenital specimens were also taken for Chlamydia trachomatis antigen detection with an enzyme-amplified immunoassay (IDEIA) and Neisseria gonorrhoeae culture. Chlamydial genital infection was found in 6% of the men and 18% of the women. All gonococcal cultures were negative. PMID- 2187795 TI - The history of the genetic sequence databases. PMID- 2187794 TI - Biological false positive serological tests for syphilis in the Jamaican population. AB - A total of 19,067 sera were screened for biological false positive (BFP) reactivity by the Venereal Disease Research Laboratory (VDRL) test. Sera which were reactive in the VDRL test were confirmed by the fluorescent treponemal antibody absorption (FTA-ABS) test. BFP reactions were detected in 0.59% of the general population, 0.72% of pregnant women and 11.8% of patients with systemic lupus erythematosus (SLE). The rate of BFP reactors among pregnant women did not differ significantly from the general population. The female to male ratio of BFP in the general population was 2:1 whilst that in the group of patients with SLE was 8:1. The overall seroprevalence of syphilis was 2.2%. PMID- 2187796 TI - Immunological identification and quantification of light harvesting chlorophyll a/b protein of Chlorella protothecoides. AB - The alteration of photosynthetic membrane proteins in relation to the disappearance of pigments during the heterotrophic growth of Chlorella protothecoides was investigated. Chlorophylls and certain polypeptides associated with the LHC II disappeared after 50 hr of heterotrophic growth but the 24 kDa apoprotein constituting LHC II was not affected. Immunological analysis indicated that the chlorophylls and the light harvesting complex proteins of the thylakoid membranes are not tightly coupled and the latter is retained in its native form irrespective of the presence or absence of the former. The circumstantial evidence that the other photosynthetic membrane polypeptides are degraded along with the pigments due to increased proteolytic activity in the rapidly dividing heterotrophic cells indicate that chlorophyll synthesis is not a pre-requisite for the synthesis of the LHC II apoprotein. PMID- 2187797 TI - Maintenance of pancreatic endocrine B cells of neonatal rat: Part-XIV--Effect of maternal hyperglycemia on the secretion of insulin and glucagon. AB - Effects of gestational hyperglycemia on A and B cells were examined in pancreatic monolayer islet cell cultures of neonatal rats from mothers of normoglycemia (C) and made slightly (SH), moderately (MH) and highly hyperglycemic (HH) by streptozotocin injection. Monolayer cultures were maintained for 7 days in the medium with 5.5 mM glucose plus 1 mM 2-deoxyglucose. On day 0, B cells of the SH group were more responsive to glucose and 2-ketoisocaproate than those of other groups. On day 7, the response of B cells in the C and SH groups was remarkably enhanced, thus displaying a dose-dependent increasing pattern of insulin secretion in response to glucose, 2-ketoisocaproate and arginine, and a convex type secretion to leucine. However, there was no response by B cells in the MH and HH groups. Further, a dose-dependent inhibition of glucagon secretion due to glucose was seen in A cells of the C and SH groups on day 0 and day 7. The responses of these A cells to other nutrients were slightly decreased or were of a low convex-type. In the MH group, however, the glucagon secretion was remarkably enhanced due to leucine and 2-ketoisocaproate on day 0 and day 7, and due to arginine on day 7, although it remained suppressed by glucose. A cells of the HH group were unresponsive through the whole culture period. These results suggest that the development of A- and B-cell responses in vitro of neonates was differently affected by the degree of maternal hyperglycemia. PMID- 2187798 TI - A testable theoretical model for magnetotherapy potentially applicative to such diverse concerns as oncogenic, CNS trophic factor and viral disorders. AB - Physiologic magnetic fields of the order 10(-8) gauss have been unified with their propitiators: quantum genetic particles, the gravitational potential of which is about an erg. As these fields are applied to the equation for solenoidal models, B = micro NI/L, currents of about a microampere are derived; in perfect accord with recent clinical data indicating the therapeutic efficacy of weak currents in repair and growth of soft tissue, bone and nerve. The mechanism of reorientation of spin angular momentum of leptons and baryons influencing molecular magnetic domains to bring about 'particle jumps' is presented so that a clinical picture results. The clinical picture is that of an organism placed at right angles to flux lines in the midst of a solenoid immersed in water exposed then to exogenously applied resonant physiologic magnetic fields which convert malalligned atomic lattices of oncogenes and associated particles to homologous normal structures. PMID- 2187799 TI - Evolution of oxygen evolving reaction center-II of thylakoids. AB - A model for evolution of oxygen evolving reaction center II of higher plant initiating from a chlorophyll--quinone complex is proposed. The reaction center gradually incorporates pheophytin, Fe and Mn to finally achieve oxidation of water to oxygen. The structural and functional pattern during evolution is proposed to descend from higher order of symmetry to lower one. PMID- 2187800 TI - A model of sustained gastrointestinal colonization by Candida albicans in healthy adult mice. AB - Three-month-old male Crl:CD1(ICR)BR and C3H/HeJ mice were fed chow containing Candida albicans for 14 days, while similar control mice were fed regular food. Stool cultures were done for all mice before and after administration of the special diet. Stool cultures were repeated 48 h, 1 week, and 1 and 3 months after stopping the diet for Crl:CD1(ICR)BR mice and again 5 months afterward for C3H/HeJ mice. Some animals were sacrificed at the end of the special diet, and cultures and histopathologic examination of various organs were performed. Colonization with C. albicans occurred in the Candida-fed mice, and the fungus was maintained in the gastrointestinal tract at a concentration of 10(3) to 10(4) CFU/g of stool for up to 5 months. There was no histologic evidence of organ infection with Candida spp. The fungus was not found in stool cultures or organs of mice in the control group. The results suggest that persistent gastrointestinal colonization of adult mice by C. albicans can be achieved without immunosuppression. Thus, with additional manipulations, this model could be useful for studying the role of gastrointestinal colonization by C. albicans in the development of systemic infection. PMID- 2187801 TI - Effect of proteolytic activity on virulence of Candida albicans in burned mice. AB - Total circulating proteolytic activity (PA) was determined by measuring the acid soluble 125I-protein fragments generated per 100 microliters of serum incubated with 125I-protein at 37 degrees C for 15 min. Normal mice had low circulating PA (1.3 +/- 0.2 micrograms/100 microliters), and burned mice had a higher average PA; the actual value depended on the time of measurement postburn. We measured the effect on mortality and on circulating PA of challenging normal and burned mice with high-virulence strain Candida albicans MY 1044 and its less virulent mutant MY 1049. Burned and normal mice challenged with a high dose (10(5)) of MY 1044 had high mortality (greater than 90%) and high circulating PA (greater than 33 micrograms generated per 100 microliters). Burned mice challenged with a lower dose (10(4] of MY 1044 had moderate mortality (63%) and lower PA (27.2 +/- 4.2 micrograms/100 microliters). All other groups of mice, including burned mice challenged with 10(5) MY 1049, had low mortality (less than 10%), and PAs were less than 22 micrograms/100 microliters. Augmentation of burned mice challenged with 10(5) MY 1049 with proteinase significantly increased mortality; with treatment of burned mice challenged with 10(5) MY 1044 with proteinase inhibitor significantly decreased mortality. We conclude that mortality correlated with total circulating PA; that the contribution to this net PA was the background PA level in the normal mice, the PA associated with the burn, and the PA caused by infection with a C. albicans strain with a particular virulence; that most deaths caused by C. albicans occurred past a PA threshold of 25 micrograms/100 microliters in the host; and that the number of burned and infected mice that died of candidiasis could be modulated by the addition of proteinases or proteinase inhibitors to the host. This last finding may lead to some novel treatments for candidiasis in burned hosts. PMID- 2187803 TI - Inhibition of Trichomonas vaginalis motility by monoclonal antibodies is associated with reduced adherence to HeLa cell monolayers. AB - Adherence of trichomonads to host epithelial cells appears to be a critical step in the pathogenesis of trichomoniasis. We evaluated the effect of a panel of 10 monoclonal antibodies on attachment of [35S]methionine-radiolabeled Trichomonas vaginalis strains to HeLa cell monolayers. Of 10 monoclonal antibodies, 3 totally eliminated motility of PHS2J strain trichomonads and reduced their adherence to 48 to 60% of control values (P less than 0.001). However, none of the monoclonal antibodies affected motility or adherence of STD13 strain trichomonads. Although the antibodies all reacted with PHS2J trichomonads by immunofluorescence, there was no correlation between inhibition of adherence and findings on either immunofluorescence or radioimmunoprecipitation. Direct microscopic observations showed that incubation with the monoclonal antibodies did not cause cytolysis of T. vaginalis. In quantitative cultures there was no difference in the number of colonies produced by parasites that had been incubated with antibodies that inhibited or had no effect on adherence. We conclude that our monoclonal antibodies reduced adherence not by cytotoxic effects or by competing for specific sites mediating adherence of the protozoa, but by inhibiting motility of T. vaginalis. PMID- 2187802 TI - Isolation and characterization of cell surface mutants of Candida albicans. AB - Mutant strains of Candida albicans were obtained by selecting for cells that escaped agglutination by a polyclonal antiserum raised against standard C. albicans serotype A isolate B311. Mutants were obtained from strains B311 and B792 and from four strains isolated from patients with acquired immunodeficiency syndrome. All 15 tested mutants retained characteristic sugar assimilation patterns. All but one of the mutants retained the ability to form germ tubes and chlamydospores. Two mutants from an acquired immunodeficiency syndrome-derived isolate were deficient in binding complement ligands iC3b and C3d, whereas another mutant was deficient in binding ligand iC3b but not C3d. The hyphae of these three mutants lacked antigens when examined by Western immunoblotting with monoclonal antibody Ca-A, which detects several glycoproteins, including C3d binding proteins. One of the complement-binding-deficient mutants was tested for its ability to colonize the gastrointestinal tract of rabbits but did not differ from the wild-type parent in site or degree of colonization. The proton magnetic resonance spectra of bulk mannan carbohydrate extracted from tested mutants showed the loss of a signal characteristic of the mannosyl alpha-PO4 linkage; each mutant also had a distinct pattern of other changes. PMID- 2187804 TI - Immune T cells sorted by flow cytometry confer protection against infection with Treponema pallidum subsp. pertenue in hamsters. AB - The role of cell-mediated immunity against infection with Treponema pallidum subsp. pertenue in humans or experimental animals is unclear. Hamsters injected subcutaneously in the hind paws with 4 x 10(6) unfractionated lymph node cells or enriched lymph node T cells (immunoglobulin negative, Ia negative) from T. pallidum subsp. pertenue-immune hamsters were resistant to challenge with T. pallidum subsp. pertenue. The popliteal lymph nodes of hamsters that received immune cells weighed less and had significantly fewer treponemes than did lymph nodes from hamsters infused with cells from nonimmune donors. Furthermore, recipients of immune T cells failed to develop antitreponemal antibodies 21 days after challenge. Enriched T cells were obtained by flow cytometric separation by using monoclonal anti-Ia antibody 14-4-4s, which identified hamster B cells. Flow cytometric analysis by two-color immunofluorescent staining with anti-hamster immunoglobulin and monoclonal anti-Ia antibody 14-4-4s confirmed that monoclonal anti-Ia antibody 14-4-4s recognized B cells. In addition, lymph node cells obtained after treatment with anti-Ia monoclonal antibody 14-4-4s and complement were 97% T cells, as determined by monoclonal antibody 20, a hamster T-cell marker. These results demonstrated that highly enriched T cells (immunoglobulin negative, Ia negative) from T. pallidum subsp. pertenue-immune hamsters conferred partial protection on hamsters against infection with T. pallidum subsp. pertenue. PMID- 2187805 TI - Cloning, sequencing, and expression of two class B endoflagellar genes of Treponema pallidum subsp. pallidum encoding the 34.5- and 31.0-kilodalton proteins. AB - Two structural endoflagellar genes of Treponema pallidum that encode the 34.5- and 31.0-kilodalton (kDa) polypeptides as detected by sodium dodecyl sulfate polyacrylamide gel electrophoresis were cloned, sequenced, and expressed. We designated these genes flaB1 and flaB3. A DNA sequence analysis of flaB1 and flaB3 showed that each gene possesses a single open reading frame that encodes a polypeptide; these polypeptides have molecular masses of 31.1 and 31.0 kDa, respectively. Shine-Dalgarno ribosome-binding sequences were identified upstream from the initiation codons of each gene. In addition, a single consensus promoter sequence was identified 121 base pairs upstream from the initiation codon of flaB1, suggesting polycistronic transcription of flaB1 and flaB3. Computer induced alignment showed that the FlaB1 amino acid sequence was identical at 206 positions (72%) to the FlaB3 sequence. Both genes were subcloned into pATH vectors and were expressed under the control of the trpE promoter. The expression products of flaB1 and flaB3 revealed fusion proteins having molecular masses of 61.0 and 59.0 kDa, respectively, which were identified on immunoblots by using specific anti-T. pallidum endoflagellar serum. PMID- 2187806 TI - Localization and activity of various lysosomal proteases in Leishmania amazonensis-infected macrophages. AB - In mammalian hosts, Leishmania amastigotes are obligatory intracellular parasites of macrophages and multiply within parasitophorous vacuoles of phagolysosomal origin. To understand how they escape the harmful strategies developed by macrophages to kill ingested microorganisms, it is important to obtain information on the functional state of parasitophorous vacuole. For this purpose, we studied the intracellular distribution and activity of host lysosomal proteases in rat bone marrow-derived macrophages infected with Leishmania amazonensis amastigotes. Localization of cathepsins B, H, L, and D was investigated by using specific immunoglobulins. In uninfected macrophages, these enzymes were located in perinuclear granules (most of them were probably secondary lysosomes) which, after infection, disappeared progressively. In infected macrophages, cathepsins were detected mainly in the parasitophorous vacuoles, suggesting that the missing secondary lysosomes had fused with these organelles. Biochemical assays of various proteases (cathepsins B, H, and D and dipeptidyl peptidases I and II) showed that infection was accompanied by a progressive increase of all activities tested, except that of dipeptidyl peptidase II, which remained constant. No more than 1 to 10% of these activities could be attributed to amastigotes. These data indicate that (i) Leishmania infection is followed by an increased synthesis and/or a reduced catabolism of host lysosomal proteases, and (ii) amastigotes grow in a compartment rich in apparently fully active proteases. Unexpectedly, it was found that infected and uninfected macrophages degraded endocytosed proteins similarly. The lack of correlation in infected macrophages between increase of protease activities and catabolism of exogenous proteins could be linked to the huge increase in volume of the lysosomal compartment. PMID- 2187807 TI - Demonstration of cross-reactivity between bacterial antigens and class I human leukocyte antigens by using monoclonal antibodies to Shigella flexneri. AB - Bacterial envelope proteins which share immunodeterminants with the human leukocyte antigen (HLA) class I histocompatibility antigen HLA-B27 may invoke spondyloarthritic disease through the process of molecular mimicry in patients expressing this phenotype. Monoclonal antibodies generated by the immunization of BALB/c mice with envelope proteins of Shigella flexneri type 2a were tested for reactivity against cultured lymphoblastoid cell lines of defined HLA phenotype. As measured by flow microfluorometry, four immunoglobulin M monoclonal antibodies reacted preferentially with HLA-B27-positive lymphocytes (HOM-2, MM) as compared with a B27-loss mutant line (1065) or cells lacking major histocompatibility complex class I antigen (Daudi, K562). Monoclonal antibodies also reacted with mouse EL-4 cells transfected with and expressing the HLA-B7 gene. Western immunoblot analysis of isolated enterobacterial envelopes demonstrated that the reactive epitope was present on bacterial proteins with an apparent relative molecular mass of 36 and 19 kilodaltons. The structural basis for the cross reactivity of bacterial antigen and HLA-B27 appeared to reside in the portion of the HLA molecule that is responsible for allotypic specificity (amino acids 63 through 83), since monoclonal antibodies were positive by enzyme-linked immunosorbent assay with synthetic polypeptides corresponding to this segment. PMID- 2187809 TI - Containment as a mechanism of nonspecific enhancement of defenses against bacterial infection. AB - Observations made during the study of nonspecific enhancement of antimicrobial host defenses permitted some physiologic dissection of the anatomic basis for normal protective processes. Local growth of bacteria in the hind limb in muramyl dipeptide-treated mice was suppressed modestly, but lymphatic filtration was markedly improved, especially between the ipsilateral groin and iliac lymph nodes. Spontaneous containment, when it occurred in saline-treated controls, proceeded similarly. Certain regional lymph nodes acted to restrict the dissemination of bacteria from an anatomically isolated infection, reducing the degree of bacteremia and improving survival. Containment of local bacterial infection appears more important in a favorable host response than does dispersion and is accentuated by muramyl dipeptide. PMID- 2187808 TI - Nonimmune binding of human immunoglobulin A to type II group B streptococci. AB - The binding of 125I-labeled human myeloma immunoglobulin A (IgA) to four type II strains and one nontypable strain of group B streptococci was measured after streptococcal chains were broken by brief sonication. Some IgA binding was observed with all strains, but specific binding (binding that was inhibited by excess unlabeled IgA, was dose dependent, and was saturable) occurred only with those strains possessing the trypsin-sensitive beta component of the c protein. Similar amounts of binding were observed with myeloma IgA and IgA1 purified from normal serum. Specific binding was more rapid at 25 degrees C than at 0 or 37 degrees C and reached a plateau in 6 to 8 h. Binding was drastically reduced (85 to 90%) when streptococci had been heated (90 degrees C for 1 h). Most radioactivity bound to group B streptococci could be displaced (greater than 60% in 3 days) by the addition of excess unlabeled IgA. The binding capacity of one strain (10(8) streptococci in 1 ml of buffer) was saturated by approximately 24 micrograms of IgA. When transformed for Scatchard analysis, these data indicated that there was a specific binding capacity of 16,000 molecules of monomeric serum IgA per single streptococcal cell. The dissociation constant for IgA binding was 19.3 nM. Since enzyme-linked immunosorbent assay studies showed that the myeloma IgA used for the studies described above was IgA1, our quantitative data apply only to the binding of this subclass to group B streptococci. However, an enzyme linked immunosorbent-filtration assay showed that both IgA1 and IgA2 bound to a type II group B streptococcus bearing the c protein. PMID- 2187810 TI - Detection of antigens with affinity for host cell membrane polypeptides in culture supernatants of Trypanosoma cruzi. AB - Parasite antigens which bind to host cell molecules of approximately 32 and 34 kilodaltons (kDa) were identified in supernatant fluids obtained from axenic cultures of Trypanosoma cruzi. These parasite components were first detected in culture supernatants obtained after 2 weeks in culture. Immunoblot analysis of culture supernatants exhibiting binding activity revealed the presence of several parasite antigens ranging in molecular mass from approximately 26 to 290 kDa. Gel filtration (Sephacryl S-300) analysis of culture supernatants revealed four major peaks, but only the highest-molecular-mass peak (containing several parasite antigens ranging from 27 to 250 kDa) possessed binding activity for the host cell molecules. PMID- 2187811 TI - Characteristics of Candida albicans adherence to mouse tissues. AB - An ex vivo binding assay originally described for determining lymphocyte homing receptors was adapted for studying Candida albicans-host cell interactions in unfixed tissue sections. BALB/cByJ mice were sacrificed, and various organs were removed, rapidly frozen on dry ice, and sectioned. C. albicans yeast cells were suspended to 1.5 x 10(8) cells per ml in Dulbecco modified Eagle medium supplemented with 5% newborn calf serum, and 100 microliters of the suspension was added to tissue sections for 15 min with rotation at 4 degrees C or at 22 to 24 degrees C. The sections were then fixed in glutaraldehyde, washed, and examined. Stationary-phase yeast cells adhered better than log-phase cells, and adherence characteristics were similar at 4 degrees C and 22 to 24 degrees C. Yeast cells from nine strains of C. albicans showed similar tissue specificity. Adherence to lymph node tissue was confined to subcapsular spaces and trabecular sinuses. In the spleen, yeast cells bound to the marginal zones. In both tissues, an association of yeast cells with tissue macrophages was suggested by results with macrophage-specific monoclonal antibodies and fluorescent or immunoperoxidase staining techniques. C. albicans adhered to convoluted tubules, glomeruli, and the tunica media of arterioles in the kidney. During experimentally induced fungemia in mice, C. albicans yeast cells associated with the same tissue sites as in the ex vivo assay, except that binding to renal arterioles was not seen in the in vivo test. A strain of Saccharomyces cerevisiae showed some adherence patterns in common with C. albicans, which indicates that tissue adherence is not sufficient for virulence. Mechanisms of attachment were not determined, but strains of C. albicans varied quantitatively in their ability to attach, and binding was inhibited by chelators of divalent cations. PMID- 2187812 TI - Expression in Escherichia coli of a high-molecular-weight protective surface antigen found in nontypeable and type b Haemophilus influenzae. AB - An Escherichia coli clone producing a high-molecular-weight surface antigen of Haemophilus influenzae type b (Hib) was isolated from a library of Hib DNA fragments cloned as lysogens in a lambda replacement vector. The antigen is found in sarcosyl-insoluble outer membrane protein preparations and was produced by all 36 H. influenzae isolates tested. Absorption studies indicated that the antigen is a surface determinant on all isolates tested. Antibodies to the antigen (D15) were found in eight of nine convalescent-phase sera from children with invasive Hib infection. Affinity-purified antibodies prepared against the cloned antigen gave protection against the development of bacteremia in a rat pup model. PMID- 2187813 TI - Opsonization of Cryptococcus neoformans by a family of isotype-switch variant antibodies specific for the capsular polysaccharide. AB - A family of immunoglobulin isotype-switch variants was isolated by sib selection from a murine hybridoma which produced an immunoglobulin G subclass 1 (IgG1) antibody specific for the capsular polysaccharide of Cryptococcus neoformans. Antibodies of the IgG1, IgG2a, and IgG2b isotypes had similar serotype specificity patterns in double immunodiffusion assays which used polysaccharides of the four cryptococcal serotypes as antigens. A quantitative difference in the ability of the isotypes to form a precipitate with the polysaccharide was observed in a double immunodiffusion assay and confirmed in a quantitative precipitin assay. The relative precipitating activity of the antibodies was IgG2a greater than IgG1 much greater than IgG2b. Analysis by enzyme-linked immunosorbent assay of the reactivity of the three isotypes with cryptococcal polysaccharide showed identical titers and slopes, suggesting that the variable region of the class-switch antibodies was unaltered. This system allowed us to examine the effect of the Fc portion of the antibody on opsonization of encapsulated cryptococci. Yeast cells were precoated with antibodies of each isotype and incubated with murine macrophages or cultured human monocytes. Antibodies of all three isotypes exhibited a dose-dependent opsonization for phagocytosis by both human and murine phagocytes. The relative opsonic activity of the antibodies was IgG2a greater than IgG1 greater than IgG2b. PMID- 2187816 TI - Polymerase chain reaction and synthetic DNA probes: a means of distinguishing the causative agents of syphilis and yaws? AB - Synthetic DNA probes specific for either the tpf-1 gene of Treponema pallidum subsp. pallidum Nichols or the tyf-1 gene of Treponema pallidum subsp. pertenue CDC 2575 were used for hybridization with in vitro-amplified chromosomal DNAs of 10 different Treponema isolates. tpf-1 and tyf-1 differ only in one nucleotide at residue 123, and three of four syphilis strains were of the Nichols type, whereas five of six yaws strains were of the CDC 2575 type, indicating that the nucleotide at position 123 of the tpf-1 or tyf-1 gene is not a definitive trait for either T. pallidum subspecies. PMID- 2187814 TI - Calcium is required for binding of Escherichia coli hemolysin (HlyA) to erythrocyte membranes. AB - The calcium requirement for hemolytic activity of Escherichia coli hemolysin was investigated by using hemolytic assays and immunoblotting of toxin-treated erythrocytes. The hemolytic activity of cell culture supernatants obtained during growth of E. coli in Luria-Bertani (LB) broth or calcium-free LB broth was calcium dependent. The hemolytic activity of culture supernatants obtained during growth in LB broth supplemented with calcium was calcium independent. Osmotic protection experiments using Dextran 4 to prevent cell lysis indicated that calcium was required for the binding of hemolysin to erythrocytes at both 4 and 37 degrees C. The binding efficiency at 4 degrees C was 50% of that occurring at 37 degrees C. The calcium-dependent binding was confirmed by immunoblotting saline-washed, toxin-treated erythrocytes with a monoclonal antibody after sodium dodecyl sulfate-polyacrylamide gel electrophoresis separation of membrane proteins. Bound hemolysin increased the calcium permeability of the cell membranes as evidenced by calcium-induced membrane protein alterations. The alterations in membrane proteins did not directly cause lysis of the cells. The results were consistent with a mechanism of lysis involving the formation of cation-selective pores in the membranes of target cells. PMID- 2187815 TI - Domains of Escherichia coli hemolysin (HlyA) involved in binding of calcium and erythrocyte membranes. AB - The primary structure of Escherichia coli hemolysin (HlyA) contains a 9-amino acid sequence which is tandemly repeated 13 times near the C terminus and which is essential for hemolytic activity. Hemolysin also requires an unknown modification by an accessory protein, HlyC, for hemolytic activity. The role of calcium in the interaction of HlyA with erythrocytes was investigated by using recombinant strains which produced inactive hemolysins unmodified by HlyC or deleted of the repeat sequences. 45Ca2+ autoradiography of the recombinant hemolysins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transferred to nitrocellulose showed that full-length, active hemolysin bound calcium. The domain involved in binding calcium was identified as the tandemly repeated sequences, since the deletion derivative missing 11 of the 13 repeats did not bind calcium. Inactive hemolysin, unmodified by HlyC, contained the repeated sequences and bound calcium as efficiently as the active, full-length toxin. The binding of the inactive toxins to erythrocytes was investigated by immunoblotting saline-washed, toxin-treated cells with monoclonal antibodies after sodium dodecyl sulfate-polyacrylamide gel electrophoresis separation of membrane proteins. The binding of full-length, active hemolysin to erythrocytes was calcium dependent. Inactive hemolysin deleted of the repeat units did not bind to cells. The inactive hemolysin, unmodified by HlyC, bound calcium but did not bind to erythrocytes. These results highlight the importance of calcium in the binding of hemolysin to erythrocytes and suggest that the binding of hemolysin to cells requires an interaction between the calcium-binding repeat domain and the modification produced by the HlyC protein. PMID- 2187817 TI - Expression of Dermatophagoides pteronyssinus allergen, Der p II, in Escherichia coli and the binding studies with human IgE. AB - Lambda gt11 clones expressing the major house dust mite allergen, Der p II, have been reported to react with IgE in the serum of a high proportion of allergic patients. The clones described, however, only produced small quantities of protein which was not fused to the beta-galactosidase of the vector. A construct of the Der p II is described which produces a fusion of Der p II, minus its leader sequence, with the glutathione-S transferase in the pGEX vector. This could be readily isolated and was shown to react with IgE in 22 of 24 patient sera showing reactivity to native Der p II, the sera not reacting having low reactivity to native protein. Absorption analysis showed that the recombinant material removed most of the IgE reactivity of patients to native Der p II. The construct described, therefore, should be valuable for quantitative studies of a pure mite allergen. PMID- 2187818 TI - Immunopathological response of C57BL/6 and C3H/HeN mice to Aspergillus fumigatus antigens. AB - C3H/HeN and C57BL/6 mice were exposed to culture filtrate (CF) and mycelial extracts (ME) of Aspergillus fumigatus (Af) intranasally. Animals received 6, 8 or 10 biweekly doses and were sacrificed 2 weeks after the last dose was administered. Specific antibodies against Af were detected in their sera by biotin-avidin-linked immunosorbent assay (BALISA). Antibodies against Af belonging to all isotypes showed an increase in both strains of mice. A progressive increase in IgG and IgA antibody isotypes against both CF and ME antigens was detected in C3H/HeN mice during the entire experimental period, whereas most antibody levels peaked after the 8th dose and remained steady or decreased slightly in the C57BL/6 strain. Lung lavage studies showed a relative decrease in the number of macrophages and an increase in the number of lymphocytes after the 6th and 8th instillation of Af antigens in both strains of mice. Histology of the lung demonstrated a progressive inflammatory reaction in C57BL/6 mice during the experimental period. On the other hand, the C3H/HeN mice showed a negligible inflammatory pulmonary reaction. The antibody responses and inflammatory changes detected in the lungs of mice exposed to Af antigens are comparable to allergic bronchopulmonary aspergillosis (ABPA) in humans and hence this model will be of value in understanding the disease mechanism in ABPA and related diseases. PMID- 2187819 TI - Postero-lateral rotatory instability in osteoarthritis of the knee. AB - Rotatory instability is well recognized following trauma to the knee, but it may also be seen in degenerative disease. The presence of chronic instability may affect the results of operative treatment of the osteoarthritic knee, as has been shown with postero-lateral rotatory instability in patients with varus deformity secondary to osteoarthritis. Recognition of these often subtle clinical entities is essential in order to improve patient selection when considering the various options for operation. An understanding of the pathomechanics of rotational instability in combination with abnormality of alignment in the joint will enable better classification of the changes which occur in osteoarthritis of the knee. PMID- 2187820 TI - Lesions produced by splinters of wood in soft tissues and bone. AB - Lesions produced by splinters of wood in the soft tissues and bones of the limbs are not uncommon and may be difficult to diagnose. A detailed history and a high index of suspicion are the key to making the correct diagnosis. Investigations are usually inconclusive. Complete excision results in prompt resolution. PMID- 2187821 TI - In memoriam Professeur Robert Merle d'Aubigne (1900-1989). PMID- 2187823 TI - High resolution computed tomography of the temporal bone in infants and children: a review. AB - Pathologic conditions involving the temporal bone in infants and children are now commonly diagnosed by computed tomography (CT). The importance of utilizing high resolution computed tomography (HRCT) with magnified, thin (1.5 mm) scans in both the axial and coronal planes is stressed in order to obtain the maximal anatomic information that is critical for proper diagnosis. A retrospective analysis of 388 cases reveals a positive diagnostic yield ranging from 65% in temporal bone trauma to 20% in clinically suspected neoplasm. Selected case reports of congenital abnormalities, inflammatory processes, traumatic lesions, and tumors will be presented. We conclude that HRCT is an excellent diagnostic modality and should be used liberally to evaluate the temporal bone in children. PMID- 2187822 TI - Sensitivity of the appetite control system in obese subjects to nutritional and serotoninergic challenges. AB - The sensitivity of the appetite system of a group of obese individuals was assessed in response to two challenges known to reduce hunger and enhance satiety in lean people. The challenges were the presentation of a caloric (high protein) load and the activation of serotonin systems. Eight obese female adults (BMI = 38) received 2 X 15 mg d-fenfluramine or placebo daily for 3 days, the study conforming to a 2 X 2 factor (drug X lunch type), double blind, repeated measures design. Three hours after dosing on day 3 they ate either a high carbohydrate (63 percent of total energy) or high protein (54 percent) lunchtime meal (the caloric load). These fixed meal challenges were equal in energy (475 kcal), weight and fat content. Ratings of hunger motivation and food preferences were tracked over the course of lunch and for a further 3 hours, at which point subjects returned for a self-selection test meal. Intakes from this second open meal revealed significant main effects of both caloric load and drug on energy intake, with the high protein d-fenfluramine combination being the most potent anorectic pairing. These findings were supported by the profiles of hunger motivation. This study has confirmed that the appetite system of these subjects was responsive to these biologically relevant challenges. The results suggest that the combination of an appetite modulating drug with specific dietary intervention may represent an effective strategy for the management of hunger arising from caloric restriction. PMID- 2187824 TI - The utility of the auditory brainstem response as a screening procedure. AB - A population of very low birthweight infants consisting of 41 infants (24 female) less than 1000 g birthweight and 108 infants (63 female) 1000-1499 g birthweight received auditory brainstem response audiometry (ABR) before initial discharge from hospital and were subsequently monitored via behavioural audiometry and tympanometry as part of their pediatric medical team follow-up assessment at age 7 months. Results support the use of ABR but indicate that its diagnostic yield was enhanced by the use of multiple ABR parameters in combination with basic audiological techniques. The commonly used single-value ABR pass/fail criterion was not found to be clinically practical. PMID- 2187825 TI - [The pathogenesis of type II diabetes mellitus]. PMID- 2187826 TI - [Hypertension and diabetes mellitus]. PMID- 2187827 TI - [Hypoglycemia in diabetes mellitus. Causes--sequelae--prevention]. PMID- 2187828 TI - [Diabetes education]. PMID- 2187829 TI - [Developments in decision support for intensified insulin therapy]. PMID- 2187830 TI - [Possibilities and risks of insulin pump therapy]. PMID- 2187831 TI - [Stage-related treatment of diabetic retinopathy]. PMID- 2187832 TI - Stereochemistry and the nature of life. Mechanist, vitalist, and evolutionary perspectives. PMID- 2187833 TI - Reperfusion and reperfusion injury in acute myocardial infarction. AB - Recognition of the clinical markers of reperfusion and comprehension of the effects of reperfusion injury in acute myocardial infarction provide a unique challenge for today's critical care nurse. In this article we will explore the processes of reperfusion injury. A review of relevant literature and presentation of a clinical case study and care plan will enable the critical care nurse to construct a larger knowledge base and assist in the nursing management of patients with acute myocardial infarction. Evaluation and treatment of reperfusion and reperfusion injury remains under investigation, but through the skills of assessment, planning, and intervention the critical care nurse can coordinate prompt and appropriate care to the patient with an acute myocardial infarction. PMID- 2187834 TI - High-permeability pulmonary edema: nursing assessment, diagnosis, and interventions. AB - High-permeability pulmonary edema (HPPE) is a problem affecting 150,000 to 200,000 critically ill patients yearly. In HPPE the alveolar-capillary membrane is injured. The resulting increased permeability of the alveolar-capillary membrane allows shifts of fluid and protein into the interstitial fluid space and alveolus. As hypoxemia develops, the nurse assesses cardinal signs and symptoms derived from the physical examination and observations. Clinical data consisting of results from various laboratory and diagnostic studies confirm the diagnosis of HPPE. Finally, nursing diagnoses can be delineated as the basis on which expert nursing care is planned and implemented. PMID- 2187835 TI - Bone seeking pharmaceuticals. PMID- 2187836 TI - [An animal experiment study using the Gore-Tex soft tissue patch as a replacement for lyophilized dura mater]. AB - Fractures of the skull base are often accompanied by dural lesions. Lyophilized dura mater is very valuable for dural reconstruction at the level of the smooth convex posterior wall of the frontal sinus, but surgery in the region of the uneven ethmoidal roof and lateral to the falx cerebri is difficult. The Gore-Tex patch is very soft and comfortable: vascular prostheses manufactured from this material have been implanted successfully for years. This material was subjected to a check of histocompatibility as a replacement for lyophilized dura in animal experiments by intracranial implantation. Lyodura is replaced by collagenous tissue, whereas Gore-Tex is incorporated by fibroblastic and osteoblastic penetration. This alloplastic material is an alternative tissue to lyophilized dura but should be reserved for special situations. PMID- 2187837 TI - A novel autoregulatory cytokine is required for the regulation of autoaggressive responses. AB - Limiting dilution studies indicate that cells with the potential to lyse autologous target cells exist in the peripheral blood of all normal individuals. In contrast to allocytotoxic cells, autocytolytic cells are down-regulated by a second less frequent cell population. When recombinant interleukin 2 is substituted for crude lymphocyte conditioned medium in these limiting dilution experiments, autocytotoxicity develops normally. Under these conditions, however, the autocytotoxic response is not down-regulated. Mixing crude lymphocyte conditioned medium together with recombinant interleukin 2 restores the regulation of autocytotoxicity normally seen at high responder cell dose. These findings indicate that a second soluble factor present in the conditioned medium is necessary either for the activation, growth, or differentiation of the regulatory cell population or alternatively, to render the cytotoxic population responsive to the activity of regulatory cells. Gel filtration studies indicate that the molecular weight of this factor is between 60 and 80 kd. This factor appears to be distinct from known immunologically active cytokines. It is conceivable that deficiencies of this cytokine may be relevant to the pathogenesis of autoimmune diseases or graft-versus-host reactions. PMID- 2187838 TI - T-cell allorecognition of HLA class II. PMID- 2187839 TI - The veterinarian is a comparative zoologist. PMID- 2187840 TI - Comparison of two sample collection methods for quantitative bacteriologic culture of canine prostatic fluid. AB - Ejaculate, urine, urethral swab specimens, and ultrasonography-guided small needle prostatic cyst aspiration and/or tissue core biopsy specimens were collected for bacteriologic culture from 25 dogs in which prostatic disease was suspected on the basis of history, clinical signs of disease, or results of physical examination. The prostate gland in each dog was examined ultrasonographically, and the tissue core biopsy specimens were examined histologically and bacteriologically. Two methods were used to assess bacterial prostatitis. In 5 dogs (20%), bacteriologic culture results of paired urethral swab and ejaculate specimens differed from culture results of specimens obtained by needle aspiration of prostatic cyst fluid or tissue core biopsy. The prostate gland in 17 dogs had 1 or more cystic, fluid-filled structures (0.5 to 4.0 cm in diameter). Ultrasonographic appearance of the prostate gland did not have obvious correlation with culture results from dogs of the study. Histologic results of prostatic tissue core biopsy specimens correlated well with culture results. PMID- 2187841 TI - Macrohematuria and life-threatening anemia attributable to subepithelial vascular ectasia of the urinary bladder in a dog. AB - Hematuria leading to life-threatening anemia was evaluated in a 9-year-old male dog. At surgery, an abnormal vessel resembling an ulcerated varicose vein was found on the surface of the bladder mucosa. After removal of the lesion, hematuria ceased and had not recurred 22 months later. PMID- 2187842 TI - Drug therapy in cats: a systems approach. AB - In the second part of this 4-part series, drug therapy in cats is discussed by use of a systems approach. Specifically, drugs that can be used safely for treatment of disorders affecting the feline gastrointestinal, central nervous, respiratory, cardiovascular, and urogenital systems are described. Many drugs that are used in dogs can be safely used in cats according to the same or similar dosing regimens. Several drugs that have traditionally been considered inappropriate (eg, morphine derivatives, primidone) can probably also be used, if cautiously, in cats. In contrast, use of several drugs that are safely used in other species should be avoided in cats (eg, selected emetics and antiemetics, phosphate salt enemas, and selected urinary antiseptics). Cats are more sensitive than dogs to the adverse side effects of a variety of drugs (eg, aspirin, digoxin, selected antiarrhythmics), and extra precautions must be taken when these drugs are used in cats. Finally, several drugs are used for the treatment of illnesses that tend to be unique to cats (eg, taurine and calcium-channel blockers in selected feline cardiovascular disorders). PMID- 2187843 TI - Yeasts in dairy products. PMID- 2187844 TI - Rapid detection of salmonellas in raw meats using a fluorescent antibody microcolony technique. AB - A fluorescent antibody-microcolony technique was developed for the rapid detection of salmonellas in pure cultures. Examination of microcolonies made the detection of salmonellas by epifluorescence microscopy easier and more reliable than using fluorescent antibody and single cells. After a study of the most effective selective enrichment media for increasing the number of salmonellas, the technique was examined with various samples of raw meats. It was able to detect salmonellas in 24 h and appeared to be as sensitive as conventional cultural techniques. Of the 101 samples studied, complete agreement was obtained with conventional methods for 94 but six apparently false positive results and one false negative result occurred. PMID- 2187845 TI - Survival of dehydrated cells of Salmonella typhimurium LT2 at high temperatures. AB - Cells of Salmonella typhimurium LT2 were dehydrated on hydrophobic membranes (Millipore FGLP2500) placed in a controlled atmosphere chamber held at 57% equilibrium relative humidity (ERH) and 37 degrees C. Dehydration for 48 h under the above conditions increased the heat resistance of Salm. typhimurium LT2 when measured as the surviving fraction after a heat challenge of 135 degrees C for 30 min. Results also showed that little or no death occurred during heat challenges of 1 h at temperatures of up to 100 degrees C. The survival of Salm. typhimurium LT2 was measured as the ability to form colonies on solid media tryptone soy broth plus 1.2% agar (TSBA) after 24 h at 37 degrees C. Incorporation of sodium pyruvate, at a concentration of (TSBA) after 24 h at 37 degrees C. Incorporation of sodium pyruvate, at a concentration of 0.2% into the recovery medium, did not enhance the recovery of heated Salm. typhimurium LT2. Dehydrated cells of S. typhimurium LT2 showed a triphasic death curve. Increasing the period of dehydration from 48 h to 34 d, reduced initial numbers due to die off but did not alter the shape of the subsequent survival curve. PMID- 2187846 TI - Ethanol fermentation by nystatin-resistant strains of Saccharomyces cerevisiae. AB - Nystatin-resistant mutants of haploid and polyploid strains of Saccharomyces cerevisiae were isolated by plating on gradient plates with increasing nystatin concentrations (60-3000 U/ml). Some of the mutants were defective in ergosterol biosynthesis, and produced zymosterol and cholestatetraenol-like sterols. Those mutants which do not form ergosterol produce less ethanol than the parent strains. They also had lower viability during fermentation of glucose solutions (8-13% vs. 33-47%). This became more pronounced in fermentations of higher concentrations of glucose. A nystatin-resistant but ergosterol-forming mutant had a similar fermentation capacity to the parent strain. PMID- 2187847 TI - Lack of precision in commercial identification systems: correction using Bayesian analysis. AB - Commercial microbial identification systems rank the relative likelihood of species identity on the basis of in vitro reactions only. Failure to consider the prevalence of individual taxa results in a spurious demotion of common species; and a tendency toward over reporting of rare microbes. The incorporation of Bayesian analysis into identification matrices can provide for a realistic ranking of bacterial species which fulfil given biocode schemes. PMID- 2187848 TI - Inhibition of the growth of enteropathogenic bacilli by bacteriocins produced by micro-organisms from the sediment of wells. AB - The bacterial flora of the sediment of 20 wells of water for human consumption in the rural area of the VII Region in Chile was examined. Fourteen strains of bacteria, from different wells, produced bacteriocins which inhibited the growth of Salmonella typhi, Salm. typhimurium, Shigella sonnei and enterotoxigenic Escherichia coli. About 50% of these strains contained plasmids of different molecular weight and a large number of these codified for bacteriocins. The results suggest what is required to implement an efficient, simple and economical biological system for the purification or control of the number of enteropathogenic bacilli of well water in the rural area. PMID- 2187849 TI - Changes in upper airway resistance with lung inflation and positive airway pressure. AB - The influence of pulmonary inflation and positive airway pressure on nasal and pharyngeal resistance were studied in 10 normal subjects lying in an iron lung. Upper airway pressures were measured with two low-bias flow catheters while the subjects breathed by the nose through a Fleish no. 3 pneumotachograph into a spirometer. Resistances were calculated at isoflow rates in four different conditions: exclusive pulmonary inflation, achieved by applying a negative extra thoracic pressure (NEP); expiratory positive airway pressure (EPAP), which was created by immersion of the expiratory line; continuous positive airway pressure (CPAP), realized by loading the bell of the spirometer; and CPAP without pulmonary inflation by simultaneously applying the same positive extrathoracic pressure (CPAP + PEP). Resistance measurements were obtained at 5- and 10-cmH2O pressure levels. Pharyngeal resistance (Rph) significantly decreased during each measurement; the decreases in nasal resistance were only significant with CPAP and CPAP + PEP; the deepest fall in Rph occurred with CPAP. It reached 70.8 +/- 5.5 and 54.8 +/- 6.5% (SE) of base-line values at 5 and 10 cmH2O, respectively. The changes in lung volume recorded with CPAP + PEP ranged from -180 to 120 ml at 5 cmH2O and from -240 to 120 ml at 10 cmH2O. Resistances tended to increase with CPAP + PEP compared with CPAP values, but these changes were not significant (Rph = 75.9 +/- 6.1 and 59.9 +/- 6.6% at 5 and 10 cmH2O of CPAP + PEP). We conclude that 1) the upper airway patency increases during pulmonary inflation, 2) the main effect of CPAP is related to pneumatic splinting, and 3) pulmonary inflation contributes little to the decrease in upper airways resistance observed with CPAP. PMID- 2187850 TI - Effects of continuous positive airway pressure breathing on lung volume and distensibility. AB - In this study the effects on lung elastic behavior of 10 min of breathing at a continuous positive airway pressure (CPAP) of 10 cmH2O were examined in 10 normal subjects. To investigate whether any changes were induced by release of prostaglandins, the subjects were also pretreated with the cyclooxygenase inhibitor indomethacin. CPAP produced a significant (P less than 0.001) upward shift of the pressure-volume (PV) curve [change in total lung capacity (delta TLC) 374 +/- 67 (SE) ml, mean delta volume at a transpulmonary pressure of 15 cmH2O (delta VL15) 279 +/- 31 ml] with no change in K, an index of lung distensibility. After CPAP the PV curves returned to normal base line within 20 min. The same pattern was observed after indomethacin, but the increase in TLC was significantly less (P less than 0.01) (mean delta TLC 206 +/- 42 ml) mainly because of a slight and not statistically significant increase in base-line TLC. In five subjects further PV curves with and without CPAP were obtained greater than or equal to 7 days after indomethacin. The responses were not significantly different from those obtained before indomethacin (mean delta TLC 366 +/- 89, mean delta VL15 296 +/- 42 ml). We conclude that CPAP produces an upward shift of the PV curve without a change in lung distensibility. In addition, there may be a small degree of resting alveolar duct tone that is influenced by indomethacin. PMID- 2187851 TI - Pleural pressure changes in dogs measured from suprasternal fossa movements. AB - Movements of the suprasternal fossa during spontaneous breathing monitored with the surface inductive plethysmograph (SIP) have been shown to reflect changes of intrapleural pressure in conscious humans. Calibration of this device in anesthetized intubated dogs was accomplished by adjusting the electrical gain of its analog waveform to be equivalent to changes of airway pressure during inspiratory efforts against an occluded airway. This procedure, denoted the occlusion test, was also used to identify the site of esophageal balloon catheter placement for its recording of intrapleural pressure deflections. The validity of SIP-derived estimates of inspiratory and expiratory pulmonary resistances and lung compliance was established by finding close agreement with measurements obtained with intraesophageal pressure changes during 1) unimpeded spontaneous breathing, 2) inspiratory resistive loading, 3) bronchoprovocation with aerosolized carbachol, 4) mechanical ventilatory modalities, and 5) induced pulmonary edema. Therefore, movements of the suprasternal fossa with respiration can be reliably transformed into quantitative or semiquantitative changes of intrapleural pressure in anesthetized intubated dogs during major alterations of pulmonary mechanics. PMID- 2187852 TI - Defining hypoxia: a systems view of VO2, glycolysis, energetics, and intracellular PO2. AB - The necessity for defining hypoxia as O2-limited energy flux rather than low partial pressure is explored from a systems perspective. Oxidative phosphorylation, the Krebs cycle, glycolysis, substrate supply, and cell energetics interact as subsystems; the set point is a match between ATP demand and aerobic ATP production. To this end the transport subsystem must match the transcapillary and mitochondrial O2 fluxes. High transcapillary O2 flux requires intracellular PO2 in the range 1-10 Torr. In this range the O2 drive on electron transport must be compensated by adaptive changes in the phosphorylation and redox drives. Thus the metabolic subsystem supports diffusive O2 transport by maintaining O2 flux at intracellular partial pressures required for O2 release from blood. Since responses to stress are distributed according to the state of the entire system, several simultaneous metabolic measurements, including intracellular PO2 (or a known direction of change in intracellular PO2) and the O2 dependence of a measurable function are required to judge the adequacy of O2 supply. ATP demand and aerobic capacity must also be evaluated, because the hypoxic threshold depends on the ratio of ATP demand to aerobic capacity. The application and limitation of commonly used criteria of hypoxia are discussed, and a more precise terminology is proposed. PMID- 2187853 TI - Mechanical effects of PEEP in patients with adult respiratory distress syndrome. AB - In 10 patients with adult respiratory distress syndrome, we studied the effects on respiratory system mechanics of two levels of positive end-expiratory pressure (PEEP), best PEEP (BP) and half of this value (HBP), using a respiratory inductive plethysmograph (RIP) combined with a super syringe. We found the following. 1) Inflation compliance of pressure-volume (PV) curves did not change significantly. 2) End-expiratory volume increased with HBP and further with BP (278 +/- 186 and 464 +/- 313 ml, respectively, P less than 0.01). This increase was positively correlated with inflation compliance for HBP and BP (r = 0.794, P less than 0.01 and r = 0.876, P less than 0.01, respectively). 3) No dynamic hyper-inflation was detected on mechanical ventilation at zero end-expiratory pressure (ZEEP), and the time constant of the respiratory system was in the normal range (0.79 +/- 0.21 s). 4) Hysteresis of PVrip curves, which were corrected for gas exchange, decreased significantly with PEEP (P less than 0.05). We conclude that PEEP does not change inflation PV curve but induces an increase in intrathoracic volume whose magnitude is related to compliance and PEEP level. The reduction of hysteresis with PEEP suggests less gas trapping and thus a functional improvement. PMID- 2187854 TI - Inhaled PAF fails to induce airway hyperresponsiveness to methacholine in normal human subjects. AB - The effects of three increasing doses of platelet-activating factor (PAF) on airway caliber and methacholine bronchial responsiveness were studied. On separate occasions nine normal subjects inhaled a single cumulative provocation concentration of methacholine (control) causing a 40% fall (PC40 Vp30) in maximum expiratory flow rate at 70% of base-line vital capacity below total lung capacity during a partial forced expiratory maneuver or 100 or 200 micrograms PAF, and seven subjects inhaled a further dose of 400 micrograms PAF. Methacholine responsiveness was measured before, at 3 and 7 h, then on days 1, 2, 3, 4, 7, 10, and 14 after each challenge. The maximum falls in Vp30 appeared dose dependent, but a significant difference between the magnitude of the responses was only observed between the 400- and 100-micrograms PAF dose (P less than 0.05). During the control period repeated methacholine challenges resulted in a progressive increase in cumulative provocation concentration of an agonist causing a 20% fall in forced expiratory volume in 1 s from base line, reaching significance on days 1 and 2 (2.44- and 2.4-fold of base line, respectively, P less than 0.01) before returning to base line on day 7. No difference was seen in methacholine responsiveness after any of the three doses of PAF compared with that after the control. We conclude that PAF causes dose-dependent bronchoconstriction but does not change airways responsiveness to methacholine and that repeated high-dose methacholine challenge leads to loss of responsiveness to this agonist. PMID- 2187855 TI - Correlation of transferrin receptor expression with histologic grade and immunophenotype in chronic lymphocytic leukemia and non-Hodgkin's lymphoma. AB - The neoplastic lymphoid cells in 33 patients with chronic lymphocytic leukemia (CLL), 1 case of prolymphocytic leukemia (PLL), and 29 patients with various types of non-Hodgkin's lymphoma (NHL) were examined for the expression of transferrin receptors (TR) using a panel of three anti-TR monoclonal antibodies (MAb). Both immunofluorescence and immunoperoxidase techniques were applied in each case. All cases of B-CLL (31) were negative for TR expression, while both the cases of T-CLL, and the only case of T-PLL showed significant TR-positive cell populations. Similarly, all 13 cases of "low-grade" NHL were TR negative, while 6 of 7 cases of "high-grade" lymphomas (lymphoblastic and immunoblastic) had up to 28% TR-positive cells. A proportion (4/9) of "intermediate grade" lymphomas had 10-15% TR positivity. Interestingly, the majority of B leukemia/lymphoma (49/55) cases were TR negative, while all 8 cases of T-cell leukemia/lymphoma were TR positive. This clearcut association of TR expression with high-risk morphologic and immunophenotypic subgroups of lymphoid leukemia/lymphoma points to the potential role of TR as a prognostic marker in lymphoproliferative disorders. PMID- 2187856 TI - Recognition sites of tRNA by a thermostable tRNA(guanosine-2'-)-methyltransferase from Thermus thermophilus HB27. AB - Recognition sites of tRNA by tRNA(guanosine-2'-)-methyltransferase (Gm-methylase) [EC 2.1.1.34] from an extreme thermophile, Thermus thermophilus HB27, were studied by two independent methods--fragment reactions and footprinting analyses, using yeast tRNA(Phe) and Escherichia coli tRNA(fMet) as substrates. None of the tRNA-derived oligonucleotides which have the G-G sequence but are not long enough to form the "stem-loop" structure could be methylated by Gm-methylase. The 5' half fragments having the intact D-"stem-loop" structure served as substrates for Gm-methylase, with a similar Vmax but 6-8 times larger Km, as compared with the intact tRNAs. The results of footprinting analyses were consistent with the foregoing findings. Gm-methylase protected only the D-loop region of tRNA from RNase T1 attack, but other parts of tRNA extending from the amino acid stem to the T arm became more sensitive to RNase T1, suggesting a considerable change of tRNA tertiary structure due to complex formation with Gm-methylase. These results indicate that a D-"stem-loop" structure is a prerequisite for recognition by Gm methylase. PMID- 2187857 TI - DNA binding properties of purified replication initiator protein (Rep) encoded by plasmid pSC101. AB - We have purified the replication initiator protein (Rep) coded by plasmid pSC101. The purified protein was confirmed to be Rep by its amino-terminal sequence. Rep exists as a dimer and has a sequence-specific DNA-binding property. Protection experiments with DNA against cleavage by DNase I or exonuclease III showed that Rep bound preferentially to two nearly dyad-symmetric sequences overlapping the promoter of the rep gene, a structure gene of Rep. Transcripts in vitro from the rep promoter were identified and the precise initiation sites were determined by the primer-extension method. Rep represses the transcription from the rep promoter but not that from the bla gene promoter in the same reaction mixture, that is the rep gene is autoregulated. The replication origin (ori) of the plasmid contains directly repeated sequences similar to the symmetric sequences. However, a one order of magnitude higher concentration of the protein is required to bind to the origin repeats. PMID- 2187858 TI - Significant amount of multicatalytic proteinase identified on membrane from human erythrocyte. AB - Multicatalytic proteinase (MCP) was solubilized from human erythrocyte membrane with 0.1% Triton X-100 and purified to homogeneity using a combination of DEAE cellulose, hydroxylapatite, and Ultrogel AcA34 chromatographies. This membranous MCP had similar properties to MCP purified in parallel from the cytosol. Both MCPs had a molecular mass of 570 kDa, were composed of apparently nine subunits of 22-36 kDa and had trypsin- and chymotrypsin-like activities. These activities were latent and required heating for the induction. However, slight differences were observed in the effects of reagents (DFP, monoiodoacetic acid, Mg2+, and Ca2+) between membranous and cytosolic MCP. The amount of MCP identified on membranes was estimated to be three-quarters or one-half of that found in the cytosol based on its trypsin- or chymotrypsin-like activity, respectively. PMID- 2187859 TI - Isolation of a yeast gene, SRH1, that encodes a homologue of the 54K subunit of mammalian signal recognition particle. AB - A 1.7 kilobase HindIII fragment of Saccharomyces cerevisiae DNA was cloned by cross-hybridization with the Escherichia coli secY gene. The complete nucleotide sequence of the 2.6 kb fragment of the yeast genomic DNA containing the cross hybridizing HindIII fragment was determined. The sequence showed no apparent similarity with that of the E. coli secY gene with the exception of a completely matched sequence of 21 bp, but it contained a 1,623 nucleotide open reading frame coding for a protein of 541 amino acids with a calculated Mr of 59,600. The N terminal portion of 303 residues of the predicted sequence was homologous to the cytosolic domain of the alpha-subunit of the signal recognition particle receptor (SR alpha), including consensus sequence elements for a GTP binding site, whereas the C-terminal portion of 238 residues had an unusual methionine-rich domain containing several repetitive sequences. An mRNA of 2.0 kb was detected on Northern blotting analysis. The predicted sequence was 48% identical with the reported sequences of the 54K subunit of the mammalian signal recognition particle (SRP54) (Romisch K. et al. (1989) Nature 340, 478-483; Bernstein, H.D. et al. (1989) Nature 340, 482-486). We designated this gene as SRH1 (SRP54 homologue). Gene disruption experiments showed that the SRH1 gene product is essential for cell growth. PMID- 2187860 TI - Sliding filaments and molecular motile systems. PMID- 2187861 TI - The carboxyl-terminal repeat domain of RNA polymerase II is not required for transcription factor Sp1 to function in vitro. AB - We show that the mammalian transcription Sp1 stimulates accurate transcription in a partially fractionated RNA polymerase II-dependent system from Drosophila cultured cells. Moreover, the extent of stimulation is equal for intact RNA polymerase II (polymerase IIA) and polymerase lacking the unique carboxyl terminal domain of the largest subunit (polymerase IIB). We conclude that in this system Sp1 interacts with a component of the transcription machinery, other than the carboxyl-terminal domain, which is preserved between mammals and insects. PMID- 2187862 TI - Efficient expression and utilization of mutant 5 S rRNA in Saccharomyces cerevisiae. AB - The expression of mutant 5 S rRNA genes in vivo is examined as a basis for further studies on the control, structure, and function of the ribosomal 5 S RNA. Specific single base substitutions (e.g. positions 98 or 99) or short insertions can result in substantial structural changes that can easily be detected by gel electrophoresis and permit the assay of mutant RNA synthesis and utilization. In addition, the use of high and low copy shuttle vectors as well as alternate growth conditions permits the adjustment of mutant RNA levels in vivo. Despite the high genomic copy number for the 5 S rRNA gene, under optimized conditions as much as 80% of the cellular 5 S RNA can be mutant, and RNA structure analyses indicate that some of these RNAs can readily be assembled into the ribosome structure resulting in an in vivo ribosome population which is also approximately 80% mutant. The results indicate that plasmid integrated 5 S rRNA genes are preferentially expressed and suggest that additional features of the chromosome structure regulate 5 S rRNA gene expression in vivo. PMID- 2187863 TI - Identification of the polyamine-induced protein as a periplasmic oligopeptide binding protein. AB - The physiological function of the polyamine-induced protein (PI protein), whose synthesis is stimulated at an early stage after the addition of putrescine to growing cells of a polyamine-requiring mutant of Escherichia coli (Mitsui, K., Igarashi, K., Kakegawa, T., and Hirose, S. (1984) Biochemistry 23, 2679-2683), has been studied. The following findings clearly show that the PI protein is a binding protein of an oligopeptide transport system. (a) PI protein was found in a periplasmic fraction. (b) When the restriction map of a clone for the PI protein gene was compared with Kohara's physical map (Kohara, Y., Akiyama, K., and Isono, K. (1987) Cell 50, 495-508), the gene was found at 27 min of the E. coli chromosome, where genes for an oligopeptide transport system were located. (c) The clone contained a 1,629-nucleotide open reading frame encoding a 543 amino acid protein whose calculated Mr was 60,901, and the predicted amino acid sequence from this open reading frame was quite similar to that of an oligopeptide binding protein of Salmonella typhimurium. (d) When the transport activity of a tripeptide, Gly-Leu-125I-Tyr, was measured in a polyamine-requiring mutant of E. coli growing both in the presence and absence of putrescine, the activity was higher in the cells growing in its presence. (e) Polyamine stimulation of cell growth was greater when an oligopeptide rather than corresponding amino acids was added to the medium. These results suggest that the polyamine stimulation of PI protein synthesis at the early stage after the addition of putrescine contributes to the polyamine stimulation of cell growth through the supply of nutrients. PMID- 2187864 TI - The amino acid sequence of the human RNA polymerase II 33-kDa subunit hRPB 33 is highly conserved among eukaryotes. AB - We have cloned and sequenced a cDNA of 1766 base pairs in length encoding the 275 amino acids of hRPB 33, the third largest subunit of human RNA polymerase II. The DNA was isolated by screening of a human lambda gt11 cDNA library with oligonucleotides designed on the basis of the amino acid residue analysis of the bovine material. The hRPB 33 amino acid sequence is highly conserved between Saccharomyces cerevisiae and human. Overall, 45% of the amino acid residues are identical with the yeast homologue RPB 3, and 65% of the amino acids are identical in the two major conserved regions at residues 0-103 and 151-197. hRPB 33 is also homologous to yeast RPC 5. The amino acid sequence of hRPB 33 showed no obvious homology with bacterial RNA polymerase or with any of its sigma factors. PMID- 2187865 TI - The functional efficiency of a mammalian signal peptide is directly related to its hydrophobicity. AB - We have previously shown that the signal sequence of the Saccharomyces cerevisiae vacuolar protein carboxypeptidase Y (CPY) does not function in mammalian cells unless a glycine residue in the central core is replaced by leucine. Additional mutants were constructed to investigate the features of this hydrophobic core (h) region that are important for signal sequence function in mammalian cells. We find that the degree of hydrophobicity of the h region of any particular mutant signal is directly related to the efficiency with which it directs the translocation of CPY. A minimal h region in a functional signal appears to consist of five hydrophobic residues interrupted by 1 glycine. Analysis of potential secondary structures suggests that a functional mutant signal is more likely than the nonfunctional CPY signal to adopt either a beta strand or an alpha-helical conformation. PMID- 2187866 TI - Characterization of an insulin receptor mutant lacking the subunit processing site. AB - An insulin receptor mutant was constructed utilizing site-directed mutagenesis to delete the Arg-Lys-Arg-Arg basic amino acid cleavage site (positions 720-723) from the cDNA encoding the human insulin proreceptor. This mutant was transfected into Chinese hamster ovary cells. Immunoprecipitation of metabolically labeled cells revealed a 205-kDa proreceptor which bound to wheat germ agglutinin. Processed 130-kDa alpha and 95-kDa beta subunits were also observed and contained approximately 20% as much protein as the proreceptor on a molar basis. Trypsin digestion of intact metabolically labeled cells decreased the proreceptor band by 80%. Pulse-chase studies revealed a half-life of 28 h for the proreceptor. When cells were photolabeled with 125I-B2(2-nitro-4-azidophenylacetyl)-des-PheB1 (NAPA)-insulin, the proreceptor incorporated 10% as much label as the 130-kDa alpha subunit in spite of a 5-fold molar excess. Incubation of NAPA-labeled cells at 37 degrees C for 20 min resulted in 60% of the labeled subunits, but little labeled proreceptor, becoming resistant to trypsin degradation. Immunoprecipitation of NAPA-insulin-stimulated cells with anti-phosphotyrosine antibodies revealed that 62% of the processed labeled receptors, but very little proreceptor, contained phosphotyrosine. Thus, this mutant receptor is synthesized, glycosylated, and expressed on the cell surface as uncleaved proreceptor, although some processing to alpha and beta subunits still occurs. It exhibits a markedly decreased affinity for insulin, and when insulin is bound to, demonstrates defective internalization, down-regulation, and autophosphorylation. These data suggest that cleavage of the mutant proreceptor into subunits is required not only for the development of high affinity binding sites, but also for normal transduction of the signal which activates the beta subunit tyrosine kinase. PMID- 2187867 TI - Role of different proteolytic systems in the degradation of muscle proteins during denervation atrophy. AB - In order to clarify the cellular mechanisms of denervation atrophy of skeletal muscle, we have studied protein turnover in denervated and control rat soleus muscles in vitro under different conditions. By 24 h after cutting the sciatic nerve, overall protein breakdown was greater in the denervated soleus than in the contralateral control muscle, and by 3 days, net proteolysis had increased about 3-fold. Since protein synthesis increased slightly following denervation, the rise in proteolysis must be responsible for the muscle atrophy and the differential loss of contractile proteins. Like overall proteolysis, the breakdown of actin (as shown by 3-methyl-histidine production by the muscles) increased each day after denervation and by 3 days was 2.5 times faster than in controls. Treatments that block the lysosomal and Ca2(+)-dependent proteolytic systems did not reduce the increase in overall protein degradation and actin breakdown in the denervated muscles (maintained in complete medium at resting length). However, the content of the lysosomal protease, cathepsin B, increased about 2-fold by 3 days after denervation. Furthermore, conditions that activate intralysosomal proteolysis (incubation without insulin or amino acids) stimulated proteolysis 2-3-fold more in the denervated muscles than in controls. Also, incubation conditions that activate the Ca2(+)-dependent pathway (incubation with Ca2+ ionophores or allowing muscles to shorten) were 2-3 times more effective in enhancing overall proteolysis in the denervated muscle. None of these treatments affected 3-methylhistidine production. Thus, multiple proteolytic systems increase in parallel in the denervated muscle, but a nonlysosomal process (independent of Ca2+) appears mainly responsible for the rapid loss of cell proteins, especially of myofibrillar components. PMID- 2187868 TI - Partial purification and characterization of bovine liver aspartyl beta hydroxylase. AB - In vitro hydroxylation of aspartic acid has recently been demonstrated in a synthetic peptide based on the structure of the first epidermal growth factor domain in human factor IX (Gronke, R. S., VanDusen, W. J., Garsky, V. M., Jacobs, J. W., Sardana, M. K., Stern, A. M., and Friedman, P. A. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 3609-3613). The putative enzyme responsible for the posttranslational modification, aspartyl beta-hydroxylase, has been shown to be a member of a class of 2-ketoglutarate-dependent dioxygenases, which include prolyl 4- and lysyl-hydroxylases. In the present study, we describe the solubilization with nonionic detergent of the enzyme from bovine liver microsomes and its purification using DEAE-cellulose followed by heparin-Sepharose. No additional detergent was required during purification. The partially purified enzyme preparation was found to contain no prolyl-4- or lysyl-hydroxylase activity. Using a synthetic peptide based on the structure of the epidermal growth factor like region in human factor X as substrate, the apparent Km values for iron and alpha-ketoglutarate were 3 and 5 microM, respectively. The enzyme hydroxylated the factor X peptide with the same stereospecificity (erythro beta hydroxyaspartic acid) and occurred only at the aspartate corresponding to the position seen in vivo. Furthermore, the extent to which either peptide (factor IX or X) was hydroxylated reflected the extent of hydroxylation observed for both human plasma factors IX and X. PMID- 2187869 TI - Sphingomyelin synthesis in rat liver occurs predominantly at the cis and medial cisternae of the Golgi apparatus. AB - The intracellular site of sphingomyelin (SM) synthesis was examined in subcellular fractions from rat liver using a radioactive ceramide analog N-([1 14C]hexanoyl)-D-erythro-sphingosine. This lipid readily transferred from a complex with bovine serum albumin to liver fractions without disrupting the membranes, and was metabolized to radioactive SM. To prevent degradation of the newly synthesized SM to ceramide, all experiments were performed in the presence of EDTA to minimize neutral sphingomyelinase activity and at neutral pH to minimize acid sphingomyelinase activity. An intact Golgi apparatus fraction gave an 85-98-fold enrichment of SM synthesis and a 58-83-fold enrichment of galactosyltransferase activity. Controlled trypsin digestion demonstrated that SM synthesis was localized to the lumen of intact Golgi apparatus vesicles. Although small amounts of SM synthesis were detected in plasma membrane and rough microsome fractions, after accounting for contamination by Golgi apparatus membranes, their combined activity contributed less than 13% of the total SM synthesis in rat liver. Subfractions of the Golgi apparatus were obtained and characterized by immunoblotting and biochemical assays using cis/medial (mannosidase II) and trans (sialyltransferase and galactosyltransferase) Golgi apparatus markers. The specific activity of SM synthesis was highest in enriched cis and medial fractions but far lower in a trans fraction. We conclude that SM synthesis in rat liver occurs predominantly in the cis and medial cisternae of the Golgi apparatus and not at the plasma membrane or endoplasmic reticulum as has been previously suggested. PMID- 2187870 TI - Transfer RNA pseudouridine synthases in Saccharomyces cerevisiae. AB - A transfer RNA lacking modified nucleosides was produced by transcription in vitro of a cloned gene that encodes a Saccharomyces cerevisiae glycine tRNA. At least three different uridines (in nucleotide positions 13, 32, and 55) of this transcript tRNA are modified to pseudouridine by an extract of S. cerevisiae. Variants of the RNA substrate were also constructed that each had only one of these sites, thus allowing specific monitoring of pseudouridylation at different nucleotide positions. Using such RNAs to assay pseudouridine synthesis, enzymes producing this nucleoside were purified from an extract of S. cerevisiae. The activities corresponding to positions 13, 32, and 55 in the tRNA substrate could all be separated chromatographically, indicating that there is a separate enzyme for each of these sites. The enzyme specific for position 55 (denoted pseudouridine synthase 55) was purified approximately 4000-fold using a combination of DEAE-Sepharose, heparin-Sepharose, and hydroxylapatite. PMID- 2187871 TI - The ANB1 locus of Saccharomyces cerevisiae encodes the protein synthesis initiation factor eIF-4D. AB - The Saccharomyces cerevisiae anaerobic gene (ANB1) is negatively regulated both by oxygen and heme. We have shown recently that an upstream repressor site located in the 5'-flanking region of this gene controls its expression (Mehta, K.D., and Smith, M. (1989) J. Biol. Chem. 265, 8670-8675). In this paper, we present the complete genomic sequence of the ANB1 locus of S. cerevisiae. The ANB1 locus encodes a protein of 157 residues with an Mr of 17, 134. The deduced amino acid sequence of the ANB1 gene product shows strikingly extensive sequence and structural homology (63.5% identical residues and an additional 15% conservative substitutions) to the 154-amino-acid-long human and rabbit eukaryotic translation initiator factor (eIF)-4D. Factor eIF-4D is the only known mammalian protein that undergoes a unique post-translational modification of Lys 50 to the amino acid hypusine, and interestingly the same lysine is also present in the ANB1 gene product. Results presented provide strong evidence that the ANB1 locus that encodes a transcript, tr-2, and a second locus encoding a transcript, tr-1, together encode two forms of yeast eIF-4D. Interestingly, heme regulates both the loci in an opposite manner; as a result it can dictate the isoform available under conditions of high and low oxygen tension. The ROX1 locus of S. cerevisiae is known to regulate CYC1, COXVb, and ANB1 genes at the transcriptional level; the ROX1 locus thus regulates all known anaerobically expressed genes that are involved in different cellular functions such as respiration and protein synthesis. PMID- 2187873 TI - Insulin modulation of hepatic synthesis and secretion of apolipoprotein B by rat hepatocytes. AB - Insulin inhibition of apolipoprotein B (apoB) secretion by primary cultures of rat hepatocytes was investigated in pulse-chase experiments using [35S]methionine as label. Radioactivity incorporation into apoBH and apoBL, the higher and lower molecular weight forms, was assessed after immunoprecipitation of detergent solubilized cells and media and separation of the apoB forms using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Hepatocyte monolayers were incubated for 12-14 h in medium with and without an inhibitory concentration of insulin. Cells were then incubated for 10 min with label, and, after differing periods of chase with unlabeled methionine, cellular medium and media labeled apoB were analyzed; greater than 90% of labeled apoB was present in cells at 10 and 20 min after pulse, and labeled apoB did not appear in the medium until 40 min of chase. Insulin treatment inhibited the incorporation of label into total apoB by 48%, into apoBH by 62%, and into apoBL by 40% relative to other cellular proteins. Insulin treatment favored the more rapid disappearance of labeled cellular apoBH with an intra-cellular retention half-time of 50 min (initial half-life of decay, t1/2 = 25 min) compared with 85 min in control (t1/2 = 60 min). Intracellular retention half-times of labeled apoBL were similar in control and insulin-treated hepatocytes and ranged from 80 to 100 min. After 180 min of chase, 44% of labeled apoBL in control and 32% in insulin-treated hepatocytes remained cell associated. Recovery studies indicated that insulin stimulated the degradation of 45 and 27% of newly synthesized apoBH and apoBL, respectively. When hepatocyte monolayers were continuously labeled with [35S]methionine and then incubated in chase medium with and without insulin, labeled apoBH was secreted rapidly, reaching a plateau by 1 h of chase, whereas labeled apoBL was secreted linearly over 3-5 h of chase. Insulin inhibited the secretion of immunoassayable apoB but not labeled apoB. Results demonstrate that 1) insulin inhibits synthesis of apoB from [35S]methionine, 2) insulin stimulates degradation of freshly translated apoB favoring apoBH over apoBL, and 3) an intracellular pool of apoB, primarily apoBL, exists that is largely unaffected by insulin. Overall, insulin action in primary hepatocyte cultures reduces the secretion of freshly synthesized apoB and favors secretion of preformed apoB enriched in apoBL. PMID- 2187872 TI - Undulin, an extracellular matrix glycoprotein associated with collagen fibrils. AB - Undulin, a novel noncollagenous extracellular matrix protein, was isolated from skin and placenta. In polyacrylamide gels most of the unreduced protein migrates with Mr above 1,000,000 yielding bands A (Mr 270,000), B1 (Mr 190,000), and B2 (Mr 180,000) after reduction. Undulin is biochemically and immunochemically distinct from other previously characterized large matrix glycoproteins. Immunoblotting using monoclonal antibodies suggests that bands A and B are closely related. Electron microscopy reveals undulin as structures consisting of an approximately 80-nm-long-tail with a nodule on one end and with one or two shorter arms on the other. Ultrastructurally immunolabeled undulin is found mainly between densely packed mature collagen fibrils. Indirect immunofluorescence shows bundles of uniform wavy fibers in dense connective tissues superimposable on a subpopulation of type I collagen structures. This suggests that undulin serves a specific yet unknown function in the supramolecular organization of collagen fibrils in soft tissues. PMID- 2187874 TI - The earliest site of iodination in thyroglobulin is residue number 5. AB - In most highly structured native proteins, as well as in thyroglobulin, the reactivity in vitro of the various tyrosyl residues toward iodine is widely different. The present work demonstrates that of nearly 70 tyrosyl residues present in rat thyroglobulin, there is one, residue number 5 from the NH2 terminal end, which has in vivo the highest affinity toward iodine, being the first one to be iodinated. In fact, when 6-(n-propyl)-2-thiouracil (PTU)-treated, iodine-deficient animals were injected with 125I and killed shortly after, we isolated from thyroid glands poorly iodinated thyroglobulin (about 1 iodine atom/thyroglobulin molecule), nearly 90% of the radioactivity of which was found as monoiodotyrosine. Although CNBr cleavage of this protein gave several fragments after gel electrophoresis only one of these, with apparent mass 27,000 Da, contained 125I. This fragment was isolated and fully characterized. Twelve cycles of automated Edman degradation were performed; the sequence found, i.e. N I-F-E-X-Q-V-X-A-Q-X-L, indicated that the 27,000-Da fragment is the NH2 terminus of thyroglobulin. This portion of the polypeptide chain contains several tyrosyl residues which may well all be potentially involved in the early iodination of the protein. The observation that the removal of seven amino acids from the NH2 terminus is accompanied (at the fifth step) by the total disappearance of radioactivity in the resulting shortened peptide suggested that the fifth residue was the only one iodinated under these conditions. A second, more quantitative experiment was performed on thyroglobulin obtained from 6-(n-propyl)-2-thiouracil treated animals whose death was postponed 24 h after the injection of 125I. In this case the radioactivity was found not only in a single CNBr fragment (27,000 Da) but also in other discrete species of lower molecular mass. The mixture of these peptides was subjected to seven steps of manual Edman degradation. Fragments before and after partial degradation were run in parallel on a polyacrylamide gel and the distribution of 125I compared. Besides some change in the background, the two profiles were identical except for the absence of the 27,000-Da species. This proves that all the 125I present in the 27,000-Da species was localized at the fifth residue, the same site at which the hormone molecule is preferentially synthesized under normal conditions. This result is not unexpected and is in accord with the known properties of thyroglobulin which has a polypeptide chain designed for efficient synthesis of the hormone even at low levels of iodination. PMID- 2187875 TI - Islet cell-specific regulatory domain in the gastrin promoter contains adjacent positive and negative DNA elements. AB - The gastrin gene is expressed in fetal pancreatic islet cells, but after birth expression is selectively repressed as the islets terminally differentiate. DNA transfection studies identified a cis regulatory domain between -108 and -76 in the gastrin promoter which controls gastrin transcription in islet cells. This cis regulatory domain comprises adjacent positive and negative elements. The negative element (-108 to -82) contains the sequence ATTCCTCT, which is also found in the negative element of the beta-interferon promoter. Gel retardation assays and DNase footprinting studies demonstrated that specific islet nuclear protein(s) bind to the gastrin negative element. In vivo competition studies demonstrated that the trans-acting factors which bind to this element specifically repress gastrin promoter activity in islet cells. Immediately downstream of the negative element lies a positive element (-82 CATATGG -76), which activates gastrin transcription in islet cells. The sequence of the positive element resembles the islet-specific enhancer elements of the insulin gene (CATCTGG/C). Gel mobility shift assays and in vivo competition studies indicate that this positive element activates the gastrin promoter by binding to the same islet cell transcription factor which binds enhancer elements in the rat insulin gene. The tandem organization of the negative and positive elements suggests that this regulatory domain may act as a switch controlling the transient transcription of the gastrin gene during fetal islet development. PMID- 2187876 TI - Axial flow velocity patterns in a pulmonary artery model with varying degrees of valvular pulmonic stenosis: pulsatile in vitro studies. AB - With the advent of noninvasive clinical techniques which can measure blood flow velocities (Doppler ultrasound), it is suggested that a fundamental knowledge of the axial flow velocity patterns in the pulmonary artery, and the changes caused by stenosis, may be used to support accurate diagnosis of valvular pulmonic stenosis. The present study was designed to characterize the axial flow velocity patterns in an in vitro model of a human adult pulmonary artery with varying degrees of valvular pulmonic stenosis. A two-dimensional laser Doppler anemometer (LDA) system was used to map the flow fields in the main (MPA), left (LPA), and right (RPA) branches of the pulmonary artery model. The study was conducted in the Georgia Tech. right heart pulse duplicator system. It was observed that the axial flow velocity patterns in the MPA and the LPA change dramatically with increasing degree of valvular stenosis. This indicates that the axial flow velocity patterns in these two branches are strongly influenced by the degree of valvular stenosis. The axial flow velocity patterns in the RPA, however, do not change much with varying degrees of valvular stenosis, indicating that the axial flow fields in the RPA are mainly influenced by the geometry of the bifurcation. It may be concluded therefore, that the changes in the axial flow velocity patterns in the MPA and LPA (rather than in the RPA) could be sensitive and reliable indicators of the severity of the defect. PMID- 2187877 TI - A double-blind trial of pulsed electromagnetic fields for delayed union of tibial fractures. AB - A total of 45 tibial shaft fractures, all conservatively treated and with union delayed for more than 16 but less than 32 weeks were entered in a double-blind multi-centre trial. The fractures were selected for their liability to delayed union by the presence of moderate or severe displacement, angulation or comminution or a compound lesion with moderate or severe injury to skin and soft tissues. Treatment was by plaster immobilisation in all, with active electromagnetic stimulation units in 20 patients and dummy control units in 25 patients for 12 weeks. Radiographs were assessed blindly and independently by a radiologist and an orthopaedic surgeon. Statistical analysis showed the treatment groups to be comparable except in their age distribution, but age was not found to affect the outcome and the effect of treatment was consistent for each age group. The radiologist's assessment of the active group showed radiological union in five fractures, progress to union in five but no progress to union in 10. In the control group there was union in one fracture and progress towards union in one but no progress in 23. Using Fisher's exact test, the results were very significantly in favour of the active group (p = 0.002). The orthopaedic surgeon's assessment showed union in nine fractures and absence of union in 11 fractures in the active group. There was union in three fractures and absence of union in 22 fractures in the control group. These results were also significantly in favour of the active group (p = 0.02). It was concluded that pulsed electromagnetic fields significantly influence healing in tibial fractures with delayed union. PMID- 2187878 TI - Ultrasound and neonatal hip screening. A prospective study of 'high risk' babies. AB - We describe a simple, quick ultrasound screening test for CDH, and its use in a prospective study of babies with a 'high risk' factor, over one year from January 1987. From a birth population of 3,879, 812 hip scans were performed on 406 babies and 98 babies were abnormal. So far, there have been no late cases of CDH. Family history, breech malposition, and postural foot deformities were confirmed to be important risk factors, but babies with a simple click were equally at risk. Our early results indicate that a large proportion of the potential late cases are contained within our extended high-risk group. PMID- 2187879 TI - Morphological changes in growth-plate cartilage in osteogenesis imperfecta. AB - We obtained specimens of growth-plate cartilage from four patients with osteogenesis imperfecta. Light microscopy showed structural changes in the tissue and morphological changes in chondrocytes and matrix, particularly in the hypertrophic zone. There were changes in the process of calcification in the primary mineralisation zone of the cartilage. We also found histochemical changes in the matrix glycosaminoglycans (GAGs) in the zones where physiological mineralisation was disturbed and where the trabeculae were interrupted and poorly mineralised. In addition to the known molecular defects in collagen, changes in GAGs and non-collagenous proteins are important factors in the pathogenesis of the disease. PMID- 2187880 TI - Pressures in the carpal tunnel. A comparison between patients with carpal tunnel syndrome and normal subjects. AB - We studied pressure in the carpal tunnel in patients with carpal tunnel syndrome and in normal control subjects, using a slit catheter and recording in the neutral position, 90 degrees dorsiflexion, and 90 degrees palmarflexion of the wrist. For each position the mean pressure in the patients was very significantly higher than in the controls, the highest pressure being in 90 degrees dorsiflexion, and the lowest in the neutral position. Using an upper limit of normal pressure of 5.5 mmHg in the neutral position gave a diagnostic sensitivity of 78.7%, a specificity of 78.1%, an accuracy of 78.5%, and a positive predictive value of 87.3%. PMID- 2187881 TI - The Matas Lecture 1989. The history of cardiovascular surgery in Australia. PMID- 2187882 TI - Ultrasound screening for abdominal aortic aneurysms in patients with atherosclerotic peripheral vascular disease. AB - The rapidly rising incidence of abdominal aortic aneurysm (AAA) and the grave prognosis in cases of rupture call for early detection and operative intervention. However, there is as yet no consensus on which groups in the population should be selected for screening. Some Authors have suggested the screening of populations at risk by virtue of their age, sex and/or the presence of arterial hypertension, and report the incidence of AAA in these populations as 5.3%, 3.4% and 0.25%, respectively. In this study we screened a group of patients with atherosclerotic peripheral vascular disease. Within this group the incidence of aneurysms was found to be 5.9%, which is at least twice the estimated incidence in the general population. Three of the six patients discovered, successfully underwent surgery. We conclude that screening of this specific population group is considerably more cost-effective than universal screening. PMID- 2187883 TI - The Leriche memorial lecture 1989. A history of open heart surgery in Japan. Experience at the University of Tokyo. PMID- 2187884 TI - Accessory mitral valve tissue: an increasingly recognized cause of left ventricular outflow tract obstruction. AB - Subvalvar left ventricular outflow tract obstruction (LVOTO) may be secondary to congenital abnormalities of the mitral valve, including abnormal attachments of the anterior leaflet of the mitral valve, parachute mitral valve, and accessory valve tissue. Successful correction of LVOTO due to accessory mitral valve tissue is reported in a 44-year-old man. Twenty-five patients with LVOTO due to accessory mitral valve tissue have been previously reported; however, only a few have been recognized preoperatively. A high index of suspicion is necessary for preoperative and intra-operative recognition and correction of the abnormality. PMID- 2187885 TI - Surgery for total anomalous pulmonary venous drainage in adults. Case reports and review of eight Japanese patients over 40 years of age. AB - In the majority of cases, total anomalous pulmonary venous drainage (TAPVD) results in death in infancy or early childhood, with very few cases surviving until adulthood. We report here the surgical correction of TAPVD in two adult patients, a 43-year-old male and 51-year-old female. The postoperative course was uneventful in the two patients, both of whom showed marked improvement of clinical features. The six other surgical corrections of TAPVD in patients over 40 years of age that have been reported in Japan are also reviewed. The favorable results in these cases were associated with the following common factors: 1) unobstructed forms with large drainage veins, 2) large interatrial communication, 3) normal pulmonary vascular resistance with normal or slightly elevated pulmonary artery pressure, 4) low grade, delayed cyanosis, and 5) the supracardiac type of TAPVD. PMID- 2187886 TI - Pseudoaneurysm of the left ventricle following mitral valve replacement. Report of two cases and review of the literature. AB - Two cases of left ventricular (LV) pseudoaneurysm following mitral valve replacement (MVR) are presented. In one patient the false aneurysm developed after an initially successful correction of intraoperative left ventricular wall rupture while the other case resulted from an apparently uncomplicated MVR performed because of staphylococcal endocarditis. Both cases were detected by combined 2-dimensional and Doppler echocardiography. The operative treatment was similar in both patients. After extirpation of the old prosthesis, the orifice of the pseudoaneurysm was closed from inside the heart, either with a Dacron patch or using interrupted sutures supported by a teflon pledget. One of the patients died one month postoperatively but the other one recovered and is clinically well 6 months after repair. She has, however, a residual communication between the LV and the pseudoaneurysm. PMID- 2187887 TI - Anaphylactic reaction associated with anti-IgA antibodies. Description of one case successfully treated by means of extracorporeal circulation. PMID- 2187888 TI - Expression of low levels of peripheral lymph node-associated vascular addressin in mucosal lymphoid tissues: possible relevance to the dissemination of passaged AKR lymphomas. AB - Lymphoid tumors display a wide variety of growth patterns in vivo, from that of a solitary extralymphoid tumor, to a general involvement of all lymphoid organs. Normal lymphocytes are uniquely mobile cells continuously recirculating between blood and lymph throughout much of their life cycle. Therefore, it is reasonable to propose that disseminating malignant lymphocytes may express recirculation characteristics or homing properties consistent with that of their normal lymphoid counterparts. Trafficking of lymphocytes involves the expression and recognition of both lymphocyte homing receptors and their opposing receptors on endothelium, the vascular addressins. These cell surface elements direct the tissue-selective localization of lymphocyte subsets in vivo into organized lymphoid organs and sites of chronic inflammation where specific binding events occur between lymphocytes and the endothelium of specialized high endothelial venules (HEV). In a recent murine study of 13 lymphoma lines, we found that lymphomas that bind well to high endothelial venules, in the Stamper-Woodruff in vitro assay (an assay of lymphocyte binding to venules in frozen sections of peripheral lymph nodes or Peyer's patches), spread hematogenously to all high endothelial venule bearing lymphoid organs, whereas non-binding lymphomas did not. In some cases lymphomas that bound with a high degree of selectivity to peripheral lymph node (PLN) high endothelial venules exhibited only limited organ preference of metastasis, involving the mucosal lymphoid organs Peyer's patches (PP) in addition to the peripheral lymph nodes of adoptive recipients. Here we demonstrate that Peyer's patch high endothelial venules express a low but functional level of peripheral lymph node addressin (MECA-79) that can be recognized by lymphomas expressing the peripheral lymph node homing receptor (MEL 14 antigen).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2187889 TI - Adenylyl cyclase in yeast: antibodies and mutations identify a regulatory domain. AB - The adenylyl cyclase system of the yeast Saccharomyces cerevisiae contains the CYR1 polypeptide, responsible for catalyzing formation of cAMP from ATP, and two RAS polypeptides, responsible for stimulation of cAMP synthesis by guanine nucleotides. We have obtained rabbit antibodies that recognize the CYR1 protein. Antibodies were raised against synthetic oligopeptides and against a recombinant beta-galactosidase/CYR1 fusion protein. These antibodies have allowed the identification of the CYR1 gene product as a 205 kDa protein. Treatment with trypsin (2 micrograms/ml) reduced the size of the CYR1 protein from 205 to 155 kDa and produced an activated enzyme which no longer responded to guanine nucleotides. This result is consistent with a model in which adenylyl cyclase activity is regulated by an inhibitory domain near the amino-terminus of the CYR1 protein. This model is further supported by the finding that adenylyl cyclase activity is also markedly elevated and unresponsive to guanine nucleotides in mutant yeast strains that express only the carboxy-terminal half of the CYR1 protein. Treatment with high trypsin concentrations (greater than 10 micrograms/ml) caused release of adenylyl cyclase activity from the membrane. Comparison of immunoreactive CYR1 fragments released by trypsin and membrane bound genetically altered proteins suggests that the CYR1 protein is attached to the membrane via a separate trypsin sensitive anchoring protein rather than via a membrane anchoring domain. PMID- 2187890 TI - Analysis of gene expression during adipogenesis in 3T3-F442A preadipocytes: insulin and dexamethasone control. AB - In the present study, we have investigated dexamethasone and insulin regulation of the expression of adipose-specific mRNA, namely, glycerophosphate dehydrogenase (G3PDH) and adipsin, at different stages of differentiation. During adipose conversion, insulin promotes an accumulation of G3PDH mRNA which is linked to cell differentiation; in fully differentiated cells, insulin is not required to maintain G3PDH gene expression. Differentiating cells in serum deprived medium already exhibit, at day 1, a maximal amount of mRNA encoding for adipsin, which is tenfold decreased by 10 nM of insulin; insulin also exerts a negative effect on the abundance of adipsin mRNA in mature cells. This result indicates that adipsin appears to be a very early marker of adipose conversion, the gene expression of which is down-regulated by the presence of insulin. Dexamethasone (DEX) decreases the G3PDH message at all stages of adipose conversion, while it promotes the accumulation of adipsin mRNA mainly in differentiating cells. In DEX-treated adipocytes, the transcription efficiency of the G3PDH gene is not altered, and reduction to 50% of the message is due essentially to an approximately twofold decrease in its half-life. PMID- 2187891 TI - Attempted measurement of the activity of selected preservative combinations. AB - The rates of kill of four commonly used preservatives, either alone or in pairs, have been determined against Escherichia coli using the viable count method. The four preservatives, employed as aqueous solutions at 25 degrees C, were benzalkonium chloride, phenylmercuric nitrate, benzyl alcohol and 2 phenylethanol. An attempt was made to quantify the results in terms of antagonism or potentiation of summed pairs, and reduction times were calculated. The usefulness of preservative combinations with regard to an improved rate of kill is demonstrated, and the use of combinations can, with wise selection, broaden the spectrum of antimicrobial activity. PMID- 2187892 TI - Therapeutic progress--review XXXVII. Methotrexate--an immunomodulator with expanding indications. PMID- 2187893 TI - [Double autoplasty of the labium majus in the surgical repair of vesico-recto vaginal fistula of obstetric origin. Apropos of 17 cases]. AB - Ten-year experience in Africa with post-delivery fistula therapy, including 39 cases of combined recto-vaginal lesions and 13 cases of laceration of perineum, prompted the author to describe a technique for surgical repair of vesico rectovaginal fistulas. Inspired from Martius' graft of already proven efficacy in the treatment of complicated vesico-vaginal fistulas, the author used the same procedure on all complex cases of combined recto-vaginal fistulas, i.e., autoplasty of the labium majus. This operation carried out intravaginally consists in utilizing a flap of fatty tissue--either a split graft or one taken separately from each labium majus, placed in contact with the suture lines of the vesical and rectal walls. This dual autoplasty performed optimally in a single step, may however also be carried out separately whenever necessary. Over a period of 4 years (1985-1989), 17 female patients were operated on using this procedure. Treatment of both fistulas, vesico- and recto-vaginal, could be achieved in 11 cases during the same operation, and in 9 cases this involved using a single split graft. 14 women recovered, including 3 who had repeated surgery (2 bladder-derived Martius grafts and one dual autoplasty). The 3 failure cases all had repeated surgery and presented quite important lesions and tissue damage. Failure was considered final in two cases and partial in one case (residual orthostatic urinary incontinence). Dual autoplasty of the labium majus has provided cure to 14 out of 17 surgical patients in one or two operations, that is, 82% of cases, which is an excellent score considering the special difficulty of treatment encountered. PMID- 2187894 TI - [War injuries of the thorax. Aggressors and wound balistics]. AB - War chest wounds are very common, but wound balistic notions are not known of physicians. Different threats are being listed, and we might retain the important rate of shrapnels wounds. Concerning the bullet behavior in soft tissue, one can discern full jacketed war bullets which may tumble after a variable "neck", and non jacketed missiles which cause wound through "mushrooming" and/or fragmentation effect. Buckshot wounds obey the rule of "all or none". Body reactions, particularly the clash with a hard material like bone, may overturn everything described in soft tissues. Every kind of possible chest wounds are analyzed from a ballistic point of view. We insist on the effects of so called terrible high velocity little bullets which do not wound because of an "explosive" shock wave, but with a fragmentation effect. The treatment sums up to the advice of good common sense which has had such a good effect on our masters. PMID- 2187895 TI - [Value and limits of bypassing the distal ileum in the treatment of hypercholesterolemia]. AB - Partial ileal bypass (PIB) was performed in 8 young adults (5 males and 3 females, mean age 37 +/- 5 years) with a history of vascular surgery (aorto coronary bypass, ACB, n = 6; stroke, n = 2), presenting with hyperlipidemia (II B: n = 7; IIA: n = 1). None of the patients had diabetes, 2 had mild hypertension, and all were cigarette smokers. Hypolipidemic drugs were discontinued prior to PIB. Following bypass surgery, patients received vitamin B12 injections twice monthly. Total plasma cholesterol (TPC) and total plasma triglycerides (TPT) were assayed at 3 months and 1 year after surgery. The mean follow-up period was 84 months. Mean TPC level was significantly lower (3.96 +/- 0.57 preoperatively vs 2.19 +/- 0.79 (p less than 0.001) and 2.54 +/- 0.76 (p less than 0.01) 3 months and 1 year postsurgery, respectively. Mean TPT level was significantly lower 3 months after the intervention (4.85 +/- 2.37 vs 2.33 +/- 0.62, p. less than 0.02), but not after one year. Similar trends were observed throughout the follow-up period. One of the ACB patients died of drowing, while three others had recurring angina pectoris symptoms. Coronary angiography showed that, despite low TPC levels, coronary artery disease had extended either to other vessels not included in the former bypass, or beyond the anastomoses. Patients with a history of stroke were asymptomatic. PIB is effective in normalizing TPC. Nonetheless, this isolated procedure is insufficient to prevent the evolution of multifactorial atherosclerosis. PMID- 2187897 TI - High-performance liquid chromatography of insulin. Accessibility and flexibility. AB - Current ideas suggest that a conformational change in the insulin monomer may play an important part in its interaction with the insulin receptor. An investigation is reported in which analytical reversed-phase high-performance liquid chromatography of insulin analogues was used to investigate the solution conformation of the insulin monomer. The results are interpreted in terms of elution coefficients modified by the calculated surface accessibilities of individual residues. The results suggest a partial unfolding of the insulin monomer under the experimental conditions used, which is consistent with current ideas on the biologically active conformation of insulin. PMID- 2187896 TI - [Wadding of the axilla in the conservative treatment of cancer of the breast. Prevention of lymphocele]. AB - A randomized prospective study was carried out on 53 consecutive female breast cancer cases hospitalized at the Centre Rene Gauducheau, In Nantes (France), with the intent of investigating whether surgical wadding of the axillary fossa with the use of proximate muscular tissue can prevent lymphocele from occurring, and avoid placement of suction drains usually required in conservative management of breast cancer. Results have been significant regarding the incidence of lymphocele (p less than 0.001), as well as the mean puncture volume and the total number of punctures needed (p less than 0.001), thus reflecting the efficacy of a simple method, which yields satisfactory cosmetic results. Failures with this method were related to the technical procedure per se, and not to its principle. The lapse of time required before additional treatment was initiated as subject to a factor not related to the method, but depended upon the recovery of normal shoulder mobilization. PMID- 2187898 TI - Purification and characterization of hementin, a fibrinogenolytic protease from the leech Haementeria ghilianii. AB - The fibrinogenolytic enzyme hementin, present in extracts of the posterior salivary glands of the giant leech Haementeria ghilianii, was isolated by ultrafiltration, high-performance ion-exchange chromatography and subsequent reversed-phase liquid chromatography. Approximately 100 micrograms (1 nmol) of hementin, present at less than 0.5% in the crude leech salivary extract, was brought to about 90% purity in three steps. Hementin migrated at an Mr of about 73,000 on non-reducing sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and at 82,000 on reducing SDS-PAGE. The amino terminal sequence was determined to be TTLTE-PEPDL. The amino terminal sequences of two inactive proteins that partially coeluted with hementin in the first chromatographic step were also determined. PMID- 2187899 TI - Determination of ditekiren, a renin inhibitor peptide, in monkey serum using high performance liquid chromatography with solid-phase extraction. PMID- 2187900 TI - Serial studies of serum interleukin-2 in chronic progressive multiple sclerosis patients: occurrence of 'bursts' and effect of cyclosporine. AB - Serum levels of immunoreactive interleukin-2 (IL-2) were determined at monthly intervals from a group of placebo- and drug-treated chronic progressive multiple sclerosis patients before and during a cyclosporine A therapeutic trial. Significantly elevated levels of the lymphokine in active patients confirmed earlier studies. The magnitude of the initial levels varied inversely with the duration of disease and predicted subsequent worsening in chronic progressive patients. In addition, the occurrence of periodic bursts of serum IL-2 was noted. Although in some patients there appeared to be a sudden drop in serum IL-2 levels with the onset of cyclosporine A medication, no effect of this drug was noted on group analysis. PMID- 2187901 TI - Why have Pneumocystis carinii trophozoites been ignored? PMID- 2187902 TI - Severe granulomatous arthritis due to spinous injury by a "sea mouse" annelid worm. AB - A case of destructive arthritis and soft tissue granulomatous inflammation occurred in a 25 year old man who had injured his right index finger while snorkelling in the Mediterranean. It was initially thought that he had fallen on a sea-urchin. He removed some spines at the time of injury but the finger became stiff, swollen, and painful, and after eight months with no symptomatic improvement amputation through the proximal phalanx was performed. Examination showed an exuberant granulomatous and foreign body type inflammation in the dermis and subcutaneous tissues and affecting the bone, with erosion of the cartilaginous surfaces of the proximal interphalangeal joint. Spines present in soft tissue sections contained no calcium but did contain chitin as shown by a von Wisseling reaction for chitosan. It is concluded that the chitinous spines almost certainly came from a sea-mouse (Phylum Annelida, family Aphroditidae). Sea mice are inconspicuous creatures which live on the sea floor and which may cause some injuries thought to be attributable to sea-urchins. PMID- 2187903 TI - Brush border enzymes in coeliac disease: histochemical evaluation. AB - Two hundred and ninety four duodenal and jejunal mucosal biopsy specimens from patients with coeliac disease, treated and untreated, and other conditions were examined histologically and by histochemical staining for five peptidase and three disaccharidase enzymes to determine profiles of activity. Suppression of activity paralleled the histology with the following enzymes: lactase, trehalase, brush border endopeptidase, dipeptidyl peptidase II and isomaltase. Lactase, trehalase, and brush border endopeptidase were specifically suppressed in untreated coeliac disease and were diagnostically useful. Examination of a combination of enzymes is recommended. PMID- 2187904 TI - Serum bactericidal resistance of faecal Escherichia coli and bactericidal competence of serum from patients with ulcerative colitis. AB - A microtitre method was developed to screen Escherichia coli from 48 patients with ulcerative colitis and 25 controls for serum resistance. Bactericidal resistance was indicated by a change in colour of indicator due to acid production by viable organisms and quantitated by a change in absorbance. The method clearly differentiated between organisms confirmed as resistant or sensitive by conventional techniques. Twenty four (50%) disease and 14 (56%) control E coli specimens showed serum resistance. Bactericidal competence of sera from patients with ulcerative colitis was assessed by incubating sensitive E coli with sera from 10 patients with ulcerative colitis and pooled normal serum. All sera effectively reduced viable counts to less than 6% of original inoculum. This study shows that serum samples from patients with ulcerative colitis are bactericidally competent and that there is no increase in the number of serum resistant E coli in patients with ulcerative colitis. PMID- 2187905 TI - Observer reproducibility in grading dysplasia in colorectal adenomas: comparison between two different grading systems. AB - The two most well known and well defined grading systems for dysplasia in colorectal adenomas were compared with regard to reproducibility. The Konishi Morson system (KMS) operates with several histological and cytological variables and grades of mild, moderate, and severe dysplasia. The Kozuka system is based on the extent of nuclear pseudostratification and also has three grades of dysplasia (III-V). As the group of severe dysplasia is very large in this system, it was extended with two higher grades, similarly based on individual histological criteria, known hereafter as the extended Kozuka system (EKS). Fifty six adenomas were graded by two observers, each observer grading twice according to the KMS criteria and twice according to EKS criteria. Intraobserver reproducibility was excellent for the KMS and moderate for the EKS, but this was not significant. The overall interobserver reproducibility was similar (moderate) for the KMS and for the EKS. Kappa values for interobserver reproducibility on individual categories were excellent for severe dysplasia according to the KMS, but low for all other categories in both systems. By simplifying both systems into two groups a high reproducibility can be obtained, but this implies that all the original grades (III-V) for the EKS must be grouped together. It is therefore recommended that a simplified KMS is used for further studies on the biological importance of dysplasia and for comparison between histological changes and other markers for colorectal neoplasia. PMID- 2187906 TI - Use of immunocytochemistry and biotinylated in situ hybridisation for detecting measles virus in central nervous system tissue. AB - Optimised immunocytochemical (ICC) and in situ hybridisation (ISH) protocols for long term, formalin fixed, central nervous system tissue infected with measles virus were developed. The effectiveness of 10 proteases for the enzymatic unmasking of formalin fixed antigen and nucleic acid was investigated. Protease VIII gave maximal signal generation with optimal tissue preservation and no background staining for both techniques. The use of a microwave oven as an additional pre-hybridisation step for RNA-RNA in situ hybridisation produced a significant increase in the number of cells labelled for genomic RNA. The ability to show the presence of antigen and nucleic acid in long term, formalin fixed tissue facilitates the use of stored necropsy material available in pathology departments for ICC and ISH investigations. PMID- 2187908 TI - Tipp-ex fluid: convenient marker for surgical resection margins. PMID- 2187907 TI - Immunohistochemical detection of neuroblastoma in frozen sections of bone marrow trephine biopsy specimens. AB - Frozen sections from bone marrow trephine biopsy specimens from children with disseminated neuroblastoma were stained using the monoclonal antibody UJ13A. An immunoalkaline phosphatase technique was the preferred staining method. Acceptable histological detail was obtained from this material and deposits of tumour cells detected. Some apparently fibrous tissue was also stained by this antibody. The results show that this immunohistological approach is feasible and provide encouragement for its addition to the range of investigations currently available for assessing the marrows of children with this disease. PMID- 2187909 TI - Fecal leukocytes in Escherichia coli O157:H7 enteritis. PMID- 2187910 TI - Clinical safety of flurbiprofen. AB - Data from 58 premarketing studies of the nonsteroidal antiinflammatory drug flurbiprofen were pooled for analyses of adverse drug reactions (ADRs). These studies included 5602 patients treated with flurbiprofen (N = 4123), aspirin (N = 1033), or placebo (N = 446) for varying durations. Diagnoses included rheumatoid arthritis, osteoarthritis, and other painful musculoskeletal conditions. In these studies serious upper gastrointestinal ADRs occurred in flurbiprofen-treated patients at less than one half the rate seen in aspirin-treated patients. The incidence of serious urinary tract ADRs was lower with flurbiprofen than with aspirin. The flurbiprofen group had no serious clinical ADRs related to the hemic/lymphatic system. The most common laboratory abnormality was a decrease in hematocrit, which occurred less often than in the aspirin group. We also evaluated serious flurbiprofen-related ADRs in 4370 patients in a variety of other studies and reviewed published reports of flurbiprofen clinical trials and case reports. These reviews showed no additional, unanticipated patterns of intolerance. These clinical safety data indicate that in the doses studied, flurbiprofen is a well tolerated agent for patients requiring nonsteroidal antiinflammatory drug therapy. PMID- 2187911 TI - Effects of antidepressants on human performance: a review. AB - Despite widespread use of antidepressants, major gaps remain in our knowledge of the effects of antidepressants on human performance. While most single-dose studies with normal subjects have suggested that the more sedating tricyclic antidepressants tend to produce impairment, the effects of antidepressant treatment in clinical populations have been less thoroughly examined, with both drug-induced impairment and improvement reported. This review suggests that factors such as age, diagnosis, drug plasma concentration, and length of treatment need to be explored to establish the effects of antidepressants on performance in clinical populations. PMID- 2187913 TI - Characteristics of biological aerosols in dairy processing plants. AB - The viable aerosol in dairy processing plant environments was characterized by using an Andersen six-stage sieve sampler and a Reuter centrifugal sampler. Artificially introduced Serratia marcescens were detected in the air during drain flooding and after rinsing the floor with a pressured water hose, thus illustrating the ability of a specific microorganism to be disseminated from drains and wet surfaces via physical disruption activities often observed in food plants. Once a high concentration of wet viable aerosol was generated, it took 40 or more min to return to the background level in the absence of forced ventilation or other activity. The greatest reduction in viable particles occurred during the first 10 min. Estimated mean aerosol particle sizes were decreased from approximately 4.6 to 3.2 mu with time lapse. The estimated mean aerosol particle sizes from actual dairy processing plant environments ranged from approximately 4.3 to 5.3 mu. In addition, a more heavily contaminated dairy processing environment contained larger aerosol particles. These results indicate that the RCS sampler will often overestimate the true aerosol concentration in highly contaminated air, because mean particle sizes are over 4 mu in diameter. PMID- 2187912 TI - Cardiovascular and symptomatic reduction effects of alprazolam and imipramine in patients with panic disorder: results of a double-blind, placebo-controlled trial. AB - Seventy-nine patients with panic disorder were randomized to an 8-week double blind treatment with alprazolam, imipramine, or placebo. Patients kept daily records of panic attacks, activity, anxiety, sleep, and medication use. Weekly measures of anxiety, depression, somatic symptoms, fears, avoidance, disability, and improvement were obtained. All patients underwent a symptom-limited exercise treadmill and other cardiovascular measures. By physician and patient global assessment, patients receiving alprazolam or imipramine were significantly better than patients on placebo. The alprazolam effects were apparent by week 1; the imipramine effects by week 4. All groups showed significant reductions in anxiety, depression, somatic measures, and panic attack frequency. At 8 weeks, patients in the alprazolam group reported significantly less fear than patients in the other two groups. Subjects in the imipramine group showed a significant increase in heart rate and blood pressure. PMID- 2187914 TI - Prognostic factors in thin cutaneous malignant melanoma. AB - A small subset of patients with thin (less than 0.76 mm thick) primary cutaneous malignant melanomas develop metastases. Features that may help differentiate higher and lower risk lesions in this thickness range are reported to include the patient's age and sex, anatomic site and diameter of the primary lesion, Clark level of invasion, development of a vertical growth phase, the mitotic index, ulceration, regression, and cellular aneuploidy. In this report, we review the literature regarding the significance of these factors on the patient's prognosis. PMID- 2187915 TI - Method of minimizing hemorrhage in excising hemangioma. AB - Subtotal excision of hemangioma may be indicated to improve contour and minimize body image distortion. A method has been employed to minimize intraoperative hemorrhage. The surgical excision is easily accomplished by using hemostatic sutures. The method is described. PMID- 2187917 TI - The politics of American health care. AB - The developments leading to the present American health care organization are traced. It is clear that hospitals have dominated at the expense of primary health care programmes. Health care costs have soared dramatically. There are particular problems inherent in a system shared between federal and state governments and a private health care industry. Attempts to provide a fully (or partially) tax-funded health service in the USA have been bedevilled by a number of factors. These include opposition from labour unions, politicians, vested interest groups and, in particular, the American Medical Association. As part of its opposition, the AMA politicized itself in 1950. But, in the political literature, American nurses are not portrayed as being very politically active. Reasons for this are explored. The introduction of Medicare and Medicaid programmes is discussed and the legal, social and political implications. Recent attempts in the USA to control costs are assessed and new trends and new problems identified. PMID- 2187916 TI - Ultrasonic propagation properties of articular cartilage at 100 MHz. AB - A pilot study on articular cartilage assessed the contributions of individual matrix components to ultrasound propagation. The influence of collagen fibril orientation and collagen cross linking was also assessed. Sections of adult bovine articular cartilage cut both parallel and perpendicular to the articular surface were examined using the scanning laser acoustic microscope (SLAM) operating at an ultrasonic frequency of 100 MHz. A set of samples was evaluated that had been sequentially treated by enzymes to (1) remove 85% of the chondroitin sulfate; (2) remove remaining glycosaminoglycans, glycoproteins, and other noncollagen proteins, leaving only the collagen fibril network; and (3) disrupt the collagen intermolecular cross links. Two striking observations were made: a profound effect of the "preferred" collagen fibril orientation on ultrasonic speed and a marked increase in attenuation coefficient when intermolecular cross links were broken in the collagen. PMID- 2187919 TI - From the museum. PMID- 2187920 TI - G. Stanley Hall and the institutional character of psychology at Clark 1889-1920. AB - This paper identifies the institutional character of pre-1920 psychology at Clark University with founding President G. Stanley Hall's active "patronage" of "outsiders," argues that the origins of this institutional character can be found in Hall's own personal character and temperament, and traces the influence of this institutional character through much of the psychology done at Clark before 1920. PMID- 2187918 TI - Pesticide contamination of ground water in the United States--a review. AB - Over 70 pesticides have been detected in ground water. Aldicarb and atrazine along with the soil fumigants EDB and DCP and DBCP have been the pesticides most frequently detected in ground water. Atrazine concentrations have been correlated with high nitrate concentrations. The triazine herbicides, simazine and cyanazine, have also been detected in ground water. The annual amount of recharge, soil type, depth of aquifer from the surface, nitrate contamination and soil pH are important field parameters in determining ground-water contamination potential by pesticides. Pesticide leaching is reduced by proper choice of crop rotation, increasing pesticide application efficiency, and integrated pest management. PMID- 2187922 TI - Homosexual studies and politics in the 19th century: Karl Maria Kertbeny. PMID- 2187923 TI - Defining the crime against nature: sodomy in the United States appeals courts, 1810-1940. PMID- 2187924 TI - Categorization in concentration camps as a collective fate: a comparison of homosexuals, Jehovah's Witnesses and political prisoners. AB - Using socio-historical data some critical features of Nazi Concentration Camps are discussed: uniqueness vs. normality; extermination vs. re-education of gay prisoners. The special fate of the Pink Triangle in comparison to other non Jewish victims is demonstrated. The determinative qualities of life and death conditions in the camps are: the National Socialist interpretation of the prisoner category; the repressive content of social control; the marginalisation in general society. The relative strength of a single influence cannot be separated one from the other. PMID- 2187925 TI - Endocytosis, intracellular trafficking, and processing of membrane IgG and monovalent antigen/membrane IgG complexes in B lymphocytes. AB - Human B lymphoblastoid cell lines specific for tetanus toxin/toxoid were used in our earlier studies to demonstrate the rapid endocytosis of monovalent Ag and its processing, as a complex with mIgG. Here we show that the mIgGR for Ag is endocytosed in the presence or absence of Ag and that at any given time about 60% of this recycling pool of membrane (m) Ig is inside the cell. During the earliest detectable stages of Ag processing a high proportion of Ag fragments resolved on SDS gels were bound to intact mIg. However, at later times, as fragmented Ag accumulated, the fragments were precipitable only with antibodies against the Fab region of mIgG indicating proteolytic fragmentation of this receptor. Fractionation of cell homogenates on self-forming Percoll gradients revealed that at least two compartments are involved in Ag processing: a low density endosome compartment and a dense "late endosome"/lysosomal compartment. The spectrum of Ag fragments observed in each fraction differed: fragments produced at later times during processing were detected only in the late endosome/lysomal fraction whereas the earliest observed fragments were found both in this fraction and in the low density fractions. Monovalent Ag/mIgG complexes appear to have an increased probability, compared to unoccupied mIgG, of targeting to proteolytically active compartments leading to processing of the Ag/mIg complex and to accelerated degradation of the mIgG. PMID- 2187926 TI - Transforming growth factor-beta and cellular immune responses in synovial fluids. AB - Mononuclear cells in synovial fluids (SF) from patients with rheumatoid arthritis and other arthropathies are characterized by functional and phenotypic changes, including impaired mitogen responsiveness and inverted ratios of CD4+/CD8+ T lymphocytes. This is related to previously described activities in synovial fluids that inhibit proliferation of lymphocytes induced by mitogens and cytokines. The present study examines the relationship of these activities and transforming growth factor beta (TGF-beta), which is now known as the most potent endogenous inhibitor of lymphocyte function. It is shown that most of the activity in SF that inhibits IL-1-induced thymocyte or T cell proliferation is neutralized by a specific antibody to TGF-beta. Analysis of the SF in the CCL64 assay, a standard test for TGF-beta, showed a close correlation between the levels of immunosuppressive activity and TGF-beta. SF contain spontaneously active inhibitors of T cell function and this is caused by the presence of active TGF-beta. Higher titers are found after transient acidification, which is known to activate the latent form of TGF-beta. Characterization of the TGF-beta isoforms showed that most of the material in SF is TGF-beta 2. Analysis of TGF beta effects on T cell subsets demonstrated that it completely inhibits proliferation of CD4+ cells whereas at the same concentrations of purified or rTGF-beta CD8+ cells are only inhibited by maximally 31.1%. SF also preferentially inhibit CD4+ Th cell proliferation and this effect is neutralized by antibody to TGF-beta. Collectively these results indicate that the presence of TGF-beta accounts for most of the immunosuppressive activities in SF and that this factor may be responsible for functional and phenotypic changes of SF lymphocytes. PMID- 2187927 TI - Recognition of human T cell leukemia virus type I (HTLV-I) gag and pX gene products by MHC-restricted cytotoxic T lymphocytes induced in rats against syngeneic HTLV-I-infected cells. AB - We established rat T cell lines expressing human T cell leukemia virus type I (HTLV-I) Ag from inbred strains of rats, WKA/H, DA, and F344, to study CTL response against the HTLV-I-infected cells. HTLV-I-specific Ag expressed in these rat cells were HTLV-I gag Ag, p19, p24, and p15, and pX Ag, p40tax and p27rex, but not env Ag, as determined by immunofluorescence and immunoblot assays. By immunization of rats with syngeneic HTLV-I-infected cells, CTL against syngeneic HTLV-I-infected cells and antibodies to HTLV-I Ag were generated in WKA/H and DA rats. The bulk CTL cultures from WKA/H and DA rats lysed specifically syngeneic SV40-transformed kidney cells infected with recombinant vaccinia viruses (RVV) expressing HTLV-I gag and pX Ag, but not those infected with RVV expressing HTLV I env Ag or a control vaccinia virus. From WKA/H rat CTL cultures, four CTL clones reactive with syngeneic HTLV-I-infected cells were isolated, three of which were specific for p27rex/p21x, but the Ag recognized by the other CTL clone was not defined with any RVV used. These results indicate that HTLV-I gag and pX gene products are recognized by MHC-restricted rat CTL specific for syngeneic HTLV-I-infected cells. PMID- 2187928 TI - Ceftriaxone vs. azlocillin and netilmicin in the treatment of febrile neutropenic children. AB - Efficacy of the cephalosporin, ceftriaxone, was compared with that of the combination of the aminoglycoside, netilmicin, and the penicillin, azlocillin, in the treatment of febrile episodes in immunocompromised neutropenic children undergoing chemotherapy for neoplastic disease. During 100 separate febrile episodes, 40 strains of bacteria were isolated from the blood of 34 patients and a further 55 strains from other sites. Nine strains (four of which were staphylococci) to both netilmicin and azlocillin. There was no difference in clinical response between the two therapeutic regimens as assessed 4 and 7 days after treatment began. Ceftriaxone had the considerable practical advantages of once daily dosage without a need for blood monitoring. Ceftriaxone would appear to be effective as initial monotherapy in the treatment of bacterial infections in severely neutropenic children. PMID- 2187929 TI - Metastatic pneumococcal endophthalmitis: report of two cases and review of literature. AB - Two patients with pneumococcal bacteraemia complicated by endophthalmitis are described. While this condition appears to have been relatively common in the preantibiotic era, a review of the literature since 1950 only identified six additional case reports. Analysis of these eight cases reveals two patterns: unilateral disease in six patients and bilateral disease with simultaneous onset in two patients. The potential pathogenic mechanisms--direct bacterial invasion or immunologically mediated processes--are discussed in relation to these clinical presentations. The critical importance of seeking ophthalmological advice early in the course of the disease is emphasised, as the risk of visual loss with systemic antimicrobials alone is very high, particularly if the infective process involves the vitreous humour. PMID- 2187930 TI - [Physiopathologic aspects of priapism. Disease or symptom?]. AB - The frequency of the iatrogenic priapism complicating the intracavernous injections of drugs for impotence has greatly improved the conceptions about priapism resulting in several novelties: a. definition: priapism may be defined as a pathological erection provoked by various anomalies of the erectile hemodynamics; a. pathogeny: at first, priapism is only the penile symptom of various diseases. Secondary and inconstantly, the priapism symptom become a priapism disease featured by an acute cavernous ischemia; c. physiopathology with two different priapisms: an unusual high flow priapism due to an acquired arteriocavernous fistula. A most usual stasis priapism due to a neuromuscular or hematological blockade of the cavernous detumescence of several origin; d. treatment: the stasis priapism alone is an genuine emergency. Puncture must be always the first treatment. If unsuccessful, the choice between pharmacological detumescence (new treatment for priapism) and surgery depends from both the physiopathological mechanisms and mainly the severity of the cavernous tissular suffering. PMID- 2187931 TI - [Descriptive epidemiology of tumors of the renal parenchyma in adults, in Indre et Loire from 1980 to 1987]. AB - 296 solid renal tumors were studied retrospectively, i.e. the total number of renal tumours diagnosed in the Indre-et-Loire region between 1980 and 1987 inclusive. The crude incidence rate increased from 5.4 per 100,000 in 1980 to 8 per 100,000 in 1987. The standardised rates were 6.7 per 100,000 for men and 3.2 per 100,000 for women. These figures being quite high for France. The mean age at the time of diagnosis, 67 years for women and 65 years for men, decreased during the study, especially for women. Patients in whom the renal cancer was discovered accidentally, tended to be older than those in whom the tumour was symptomatic. The percentage of tumours discovered at stage I rose from 29 to 49% the percentage of tumours at stage IV fell from 45 to 23.5%. In parallel, the percentage of nephrectomies rose from 40 to 70%. The overall 5 year survival rate was 43.5%, rising to 71% for stage I tumours. It appeared that patients who consulted in the private sector tended to be younger and were therefore at an earlier stage in the natural history of the disease. From an epidemiological viewpoint, the introduction of ultrasonography in the Indre-et-Loire region and its more widespread use did not produce any change in the means of diagnosis of renal cancer. PMID- 2187932 TI - [Autotransplantation in the treatment of isolated dissection of the renal artery]. AB - Isolated dissection of renal artery is uncommon; 150 cases were reported in the literature, whose 2/3 diagnosed during patient's life and 1/3 post mortem, during autopsy. From 1976 to 1988 4 cases of isolated dissection of the renal artery were diagnosed and treated in our Institution. Three men and one woman with age ranging from 39 to 46 yrs (mean age 41.75) were seen at our Institution for intense abdominal pain and blood hypertension (mean blood pressure 196.25/113.75 mmHg) of recent occurrence. In 2 cases angiography showed dissection of the left renal artery, with involvement of peripheral branches; in 1 case the dissection involved the right renal artery with complete occlusion of an upper pole branch and upper pole infarction; our youngest patients presented a bilateral dissection, limited to the main trunk on the right side and involving prepelvic and retropelvic branches on the left side. Surgical treatment consisted of renal autotransplantation in the iliac fossa after extracorporeal reconstruction of the arterial pedicule; a branched hypogastric graft was used in 3 patients; in the patient with bilateral dissection an hypogastric graft was used on the right side and a sapehenous graft on the left side (3 months later). Partial nephrectomy was also performed in the patient having right upper pole infarction. Histologic examination showed that dissection always started from lesions of the lamina media. All patient were alive from 6 to 48 months after renal revascularization, with normalization of blood pressure (mean BP 125/80 mmHg); postoperative angiographic control showed thrombosis of 2 small branches in 1 case and partial stenosis of 3 anastomoses in another patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2187933 TI - Excessive cancer rates among blacks in Louisiana: an opportunity for physician intervention. AB - Excessive cancer rates among blacks in Louisiana are well-documented. Both male and female blacks have higher overall cancer incidence and mortality rates than their white counterparts. Cancers that are excessive in males include lung, esophagus, larynx, stomach, pancreas, liver, multiple myeloma, and prostate. In black females, higher rates are observed for cancers of the esophagus, stomach, pancreas, liver, multiple myeloma, cervix, and breast (mortality only). The excess of lung cancer among black men is not observed in women. These cancer sites share similar risk factors and are associated mostly with tobacco or diet. Physicians in Louisiana can play an important role in cancer intervention by informing their black patients about the magnitude of the cancer problem in blacks, increased cancer risk associated with tobacco and excessive alcohol use, importance of a balanced nutritious diet, cancer signs and symptoms, and the importance of early detection. PMID- 2187934 TI - Cancer mortality in the 30s foretells cancer of the 80s in Louisiana. AB - Examination of secular trends suggests that the high cancer mortality rates of the 1980s could have been foretold by the excessive rates in the 1930s in Louisiana. Those same sites which were excessive in the 1930s, reflecting exposure to risk factors in the early 1900s, still predominate in the 1980s. Because of the poor survival associated with lung cancer and the increase in smoking, the increase in lung cancer had the greatest impact on the mortality trend in the all sites combined category. The stability of the cancer problem and the lack of progress in reducing cancer over the last 50 years is seen as a harbinger of the cancer problem over the next 50 years. PMID- 2187935 TI - PDQ: the National Cancer Institute's computerized database for physicians. AB - Physician Data Query (PDG) is the National Cancer Institute's computerized database of current information regarding cancer treatment consisting of four major files: (1) a cancer information file providing prognostic and treatment information on all major cancers; (2) a protocol file containing investigational and standard therapy protocols; (3) a physician directory of 10,000 physicians devoting a major portion of their clinical practices to cancer treatment; and (4) a directory of approximately 2,000 organizations and institutions providing care to cancer patients. While PDQ's primary user group is practicing physicians requiring information for patient care, it can be of use to other health professionals. Searches are rapid, inexpensive, and can be performed through medical and hospital libraries, via individual direct accession, or in conjunction with other online vendors. PMID- 2187936 TI - Tinnitus. AB - Although tinnitus is usually a benign finding, it can have an extremely adverse effect on a patient's life. Tinnitis is a symptom that can have many different etiologies. This communication deals with the etiology, diagnosis, and available treatment of the condition. PMID- 2187938 TI - Barnes Hospital at Washington University Medical Center, St. Louis, Missouri. PMID- 2187937 TI - Demonstration of a thrombocytopenic factor in the blood of patients with thrombocytopenic purpura. 1951. PMID- 2187939 TI - A pessimistic outlook. PMID- 2187940 TI - Neuro-axonal recruitment: a result of selective compression. AB - Many acoustic neurinomas and CPA tumours present an audiometric picture of positive-recruitment hearing impairment although often the CMs are not significantly impaired (according to ECochG) and because, even in the case of a small acoustic neuroma, the interpeak latency between wave I and V (ERA) is increased in the majority of cases. Recruitment cannot be explained, in these cases, as an expression of an accompanying vascular inner ear lesion. Therefore, we attempt to interpret the differential audiometric picture to the various patterns of damage of the auditory nerve. The finding of tone decay is seen as an expression of myelin damage corresponding to the hearing loss in multiple sclerosis. The absence of any degree of tone decay excludes an isolated damage of the myelin sheaths; hearing loss then results from a disturbance also of the associated axons. At such a stage, where there is a functional loss to part of the neural fibres but with intact myelinated residual fibres, the result could be the phenomenon of recruitment for suprathreshold stimulation. This theory of selective compression is compared to an isolated efferent lesion theory as the cause for recruitment in AN and CPA tumours. PMID- 2187941 TI - Inferior turbinectomy: comparison of four techniques. AB - As yet, there is not totally satisfactory means for treating hypertrophied turbinates and the proper management of turbinate dysfunction remains in question. In the present series, four of the widely practiced surgical procedures for the reduction of the size of the inferior turbinates were evaluated and compared. In all cases turbinectomy was performed as an isolated procedure. Eighty patients with chronic non-allergic rhinitis and hypertrophied inferior turbinates were selected, randomly divided into four groups, and followed up post operatively for one year. Study of the results indicated that the beneficial effect of the operation is mainly mechanical by reduction of the resistance to nasal airflow. The post-operative improvement in smell acuity correlated positively with the increased patency of the nasal airway. None of the procedures had a deleterious effect on olfactory acuity. In contrast, the operation failed to enhance the mucociliary clearance rate or significantly decrease nasal drainage. Partial inferior turbinectomy and laser turbinectomy improved nasal breathing in 77 per cent of patients, and enhanced olfactory acuity in 78 per cent of patients who had pre-operative hyposmia. The results of turbinoplasty and cryoturbinectomy were less favourable. The surgical technique, advantages, and drawbacks of each of these procedures are discussed. PMID- 2187942 TI - Sinusitis and the acute orbit in children. AB - Acute orbital infection is an uncommon condition which is often secondary to acute sinusitis. Although it can present in any age group it is most prevalent in children and may cause impaired vision, blindness, intracranial complications and death. This paper documents the experience at the Royal Liverpool Childrens Hospital, Alder Hey, from 1973 to 1989. Clinical details were recorded retrospectively from the hospital case notes. Sixty-eight children had orbital sepsis of whom 30 had associated acute sinusitis. Of these 30 children, orbital sepsis was always unilateral with a preference for the left side; ten had diplopia of whom four had a sub-periosteal abscess which was subsequently drained. There were no serious complications although two children had diplopia for two to three months. PMID- 2187943 TI - Tracheal stenosis in infants and young children. AB - Eight cases of intra-thoracic tracheal stenosis presenting to the ENT department at the Hospital for Sick Children, Great Ormond Street, over the past 10 years are reported. The varied aetiology and presentation of these cases is discussed and the frequency of associated cardio-pulmonary anomalies emphasized. Difficulties in diagnosis and investigation are outlined, in addition to an overview of current management. While the overall outlook for many of these children remains poor there is reason to believe that a balance of conservative management and surgical reconstruction in selected cases will result in improved survival figures. PMID- 2187944 TI - Securing of suctions drains in head and neck surgery. PMID- 2187945 TI - Changes in blood lipids during six days of overfeeding with medium or long chain triglycerides. AB - Although medium chain triglyceride (MCT) is less calorically dense than long chain triglyceride (LCT), it produces a greater thermic effect following ingestion. We hypothesized that the previously observed high rate of thermogenesis produced by MCT overfeeding was due to hepatic de novo synthesis of long chain fatty acids (LCFA) from the excess medium chain fatty acids (MCFA). To study this, we compared the effects of overfeeding MCT- and LCT-containing diets on blood lipid profiles. Ten in-patient, nonobese males were overfed (150% of estimated energy requirements) two formula diets for 6 days each, in a randomized crossover design. Diets differed only in the composition of the fat and contained either 40% of energy as MCT or LCT (soybean oil). The major differences between diets in the resulting pattern of blood lipids were: 1) a reduction in fasting serum total cholesterol concentrations with the LCT, but not the MCT diet; and 2) a threefold increase in fasting serum triglyceride concentrations with MCT, but not LCT, diet. Moreover, 10% of the fasting triglyceride fatty acids were medium chain and 40% were 16:0 with the MCT diet. This compared to 1% and 20% for medium chain and 16:0, respectively, with the LCT diet. In addition, there were increases in 16:1, 18:0, and 18:1 in the triglycerides during MCT feeding. The changes in fatty acids in triglycerides with MCT feeding are consistent with the hypothesis that excess dietary MCT cause a significant increase in the hepatic synthesis of these fatty acids from MCFA through de novo synthesis and/or chain elongation and desaturation. These processes could account for the higher rate of postprandial thermogenesis with MCT as compared to LCT. PMID- 2187946 TI - The value of body surface potential maps in detecting abnormal ventricular wall motion. AB - In an effort to enlarge the clinical application of body surface potential maps (BSPMs), the authors studied the relationship between abnormal ventricular wall motion and BSPMs in 98 consecutive patients with angiographically proven coronary artery disease (CAD). Forty-nine of the patients (50%) had wall motion abnormalities as seen on single-plane left cine ventriculograms. During early ventricular depolarization, normal BSPMs have a potential maximum that is greater than the absolute value of the potential minimum; this reverses in late depolarization such that the absolute value of the potential minimum is the greater. The patients showed a significantly early reversal (p less than 0.001), and 55 (56.1%) had abnormal "early reversal" BSPMs. This abnormal "early reversal" is closely related to abnormal ventricular wall motion. Using it as an indicator of abnormal wall motion, the authors obtained the sensitivity, specificity, positive predictive value, and negative predictive value of the following conditions: LAD lesions, LCX, RCA, LAD and RCA lesions, LAD and LCX, and three-vessel disease, and for all patients. A relatively high sensitivity (85%) and specificity (80%) was found in patients with LAD lesions only or multivessel lesions in addition to LAD lesions. PMID- 2187947 TI - Microdialysis--a novel technique for clinical investigations. AB - Microdialysis is a novel, non-traumatic technique which, when properly performed, allows continuous direct measurements of substances in the interstitial space of a tissue or organ. It also makes it possible to obtain protein-free fluid for analyses, while contaminating bacteria or viruses are excluded. The measurements provide us with an insight into metabolic and pharmacological events at the cellular level in a target organ. Apart from its usefulness for experimental work, it is likely to become an important tool for defined areas in clinical practice. PMID- 2187948 TI - Prevention of myocardial infarction and stroke in patients with intermittent claudication; effects of ticlopidine. Results from STIMS, the Swedish Ticlopidine Multicentre Study. AB - The Swedish Ticlopidine Multicentre Study (STIMS) was a double-blind placebo controlled trial designed to determine whether ticlopidine, a platelet antiaggregatory agent, reduces the incidence of myocardial infarction, stroke and transitory ischaemic attacks in patients with intermittent claudication. A total of 687 patients was monitored for a minimum of 5 years or until an end-point was reached. The number of end points (99 vs. 89), analysed according to the intention-to-treat principle, was 11.4% lower in the ticlopidine group (P = 0.24). The mortality rate was 29.1% lower in the ticlopidine group (64 vs. 89, P = 0.015); this observation could be accounted for by a reduced mortality from ischaemic heart disease. On-treatment analysis showed there to be significantly fewer end points in the ticlopidine group (47 vs. 76, P = 0.017). Diarrhoea was the most common side-effect. Reversible leucopenia or thrombocytopenia was reported in seven patients on ticlopidine. It is concluded that the high morbidity and mortality from cardio- and cerebrovascular disease in patients with intermittent claudication can be reduced by long-term treatment with ticlopidine. PMID- 2187949 TI - Blocking-ELISA for detection of specific antibodies to the glycoproteins of the human immunodeficiency virus type 1 (HIV-1). AB - A blocking ELISA was developed to confirm the specificity of screening tests for anti-HIV-1 antibodies. A murine monoclonal antibody (McAb) raised against recombinant gp160 was used in combination with a commercial technique (ELA-VIA 1). After determining the optimal experimental conditions, the assay was applied to 92 samples presenting different reactivities by Western blot (WB) analysis. All the sera containing antibodies to gp160/gp120 (53) were positive in our assay. The six patients who sero converted showed a low positivity by ELAVIA-1 (optical density near the cutoff value) reacted by blocking-ELAVIA-1 with an McAb binding inhibition greater than 85%. By contrast, negative samples (29) and specimens that exhibited reactivity only against gag-proteins (10) were not detected (McAb binding inhibition smaller than 15%). This sensitive and specific blocking-ELAVIA-1 represents a convenient alternative to WB as a confirmatory test. The technique is time-saving and inexpensive and can easily be integrated with a screening test for diagnostic or epidemiologic studies on HIV-1 infection. PMID- 2187950 TI - Episodic paroxysmal hemicrania: a further case and review of the literature. AB - Episodic paroxysmal hemicrania was delineated as a clinical entity only two years ago, separating patients whose attacks remained grouped in bouts lasting weeks, from those who started irregularly and lapsed into chronicity or began and continued in the chronic state. A further case of the episodic variety and a review of the nine previously recorded cases is reported. The division into episodic and chronic variants of paroxysmal hemicrania conforms with the classification of cluster headache. The similarity of the two conditions is emphasised although the response to indomethacin in paroxysmal hemicrania is a special feature. PMID- 2187951 TI - Aneurysm re-rupture: Doppler evidence of first phase vasospasm? PMID- 2187952 TI - The effect of a bacterial vaccine on tumors and the immune response of ICR/Ha mice. AB - This study examined the effect of mixed bacterial vaccine (MBV), a biological response modifier prepared from Streptococcus pyogenes and Serratia marcescens, on the immune system of mice and on the regression of a transplantable mouse tumor sarcoma 37. The study examined MBV's biological properties and analyzed its chemical composition. The chemical composition varied with the growth media. A typical centrifuged, dialyzed supernate of the serum-containing preparation was found to consist mainly of protein and minimal amounts of carbohydrate and endotoxin, while MBV made with synthetic medium contained similar amounts of all three. MBV was nontoxic for mice, which gained weight following the injection of 0.5-1.0 ml of MBV. MBV caused regression of 20-100% of well-established mouse tumors without appreciable toxicity. MBV also had a striking effect on the immune response of mice to sheep red blood cells. When administered simultaneously with antigen injection, MBV increased the number of antibody-secreting splenocytes measured by the plaque-forming assay threefold. Serum antibody levels also increased two- to threefold. MBV did not enhance the immune response to pneumococcal polysaccharide type III, a B-cell-dependent response. However, the in vivo administration of MBV increased the in vitro response to MBV and the B cell mitogen lipopolysaccharide. MBV compares favorably with other biological response modifiers because of its enhancing effect on the immune response and its oncolytic properties at nontoxic levels. PMID- 2187953 TI - Dissociation of thymidine incorporation and transferrin receptor expression from cell growth and c-myc accumulation in alpha-interferon-treated cells. AB - Alpha-interferon is capable of altering the pattern of growth of both normal and neoplastic cells, but the pathways essential to sensitivity and resistance to alpha-interferon are unknown. To explore the growth inhibition induced by alpha interferon, we examined the interferon-sensitive cell line Daudi and the resistant cell line HL-60. In Daudi, alpha-interferon induced a fall in c-myc mRNA accumulation at 24 h, inhibited tritiated thymidine ([3H]Thd) uptake at 48 72 h, and inhibited proliferation at 72-96 h. The half-life of c-myc mRNA was shortened from 31 to 13 min by alpha-interferon treatment. In HL-60, no alteration in c-myc accumulation or cell growth was observed, but [3H]Thd uptake was inhibited by 49%. Exogenous thymidine partially reversed the effects of alpha interferon on [3H]Thd incorporation. The number of transferrin receptors, as measured by immunofluorescence, was unaffected by alpha-interferon in both cell lines. We conclude that the growth inhibitory effects of alpha-interferon are neither dependent upon inhibition of thymidine metabolism nor on expression of the transferrin receptor, but may be linked to control of c-myc. PMID- 2187954 TI - Society honors Marcus E. Raichle, MD, for basic science achievement. PMID- 2187955 TI - Danish pioneer in cerebral blood flow studies to receive 1990 Hevesy award. PMID- 2187956 TI - Quantitative assessment of blood flow in pediatric recipients of renal transplants. AB - We applied a renal blood flow (RBF) quantification technique to pediatric data, which depends minimally on bolus shape, uses a conventional radiopharmaceutical 99mTc-DTPA, and generates a value for RBF as a percentage of cardiac output (RBF/CO). Mean RBF was 16.9% (+/- 4.8) for normal transplants, 13.1% (+/- 2.9) for transplants undergoing mild-to-moderate chronic rejection, 7.9% (+/- 1.3) for those with mild acute rejection and 3.3% (+/- 1.4) for those with moderate-to severe acute rejection. Very low blood flow values within 24 hr following transplantation may have prognostic significance. Patients who required transplant-nephrectomy had significantly lower RBF/CO values than children who retained their allograft. PMID- 2187957 TI - Effect of glucose on the distribution of iodine-123-IHA-16 between esterification and oxidation in canine myocardium. AB - To evaluate the effect of glucose perfusion on the myocardial metabolism of [123I]-16-iodo-9-hexadecenoic acid (IHA), the latter was injected intravenously into six fasting dogs perfused with a solution lacking glucose (controls) and seven fasting dogs perfused with glucose and insulin. The distribution of myocardial 123I among iodides, free IHA, and esterified IHA was measured in myocardial biopsy specimens. The increase in esterification and decrease in oxidation of IHA due to glucose were quantified using a compartmental mathematical model of myocardial IHA metabolism. Subsequently, in six control and six glucose-perfused dogs, cardiac radioactivity was measured with a scintillation camera for 1 hr following i.v. injection of IHA. Four different methods were used to analyze the myocardial time-activity curves and to calculate the distribution of IHA between oxidation and esterification. Results comparable to those provided by analysis of biopsy specimens can be obtained by considering the curve to be the sum of an exponential and a constant, or by analyzing it with a compartmental mathematical model. PMID- 2187958 TI - Renal scintigraphy in renovascular hypertension secondary to stenosis of a supplemental renal artery. PMID- 2187959 TI - Radionuclide imaging of joint inflammation in the '90s. PMID- 2187960 TI - Cholesterol metabolism, digestion rates and postprandial changes in serum of swine fed purified diets containing either casein or soybean protein. AB - Swine fitted with re-entrant ileo-cecal cannulas were fed purified diets containing either casein or soybean protein to study possible relations between cholesterol metabolism, digestion of dietary constituents and postprandial patterns of various serum components. Compared with soybean protein, dietary casein produced an increase in serum total cholesterol in which the excess cholesterol was located in the low density lipoprotein fraction. Ileal and fecal excretion of neutral steroids was diminished in pigs fed casein, suggesting that cholesterol absorption was stimulated. The apparent ileal absorption of protein was increased in pigs fed casein. The enhanced absorption of cholesterol and protein was associated with a reduced rate of flow of chyme through the ileum. The output of bile acids in the feces of pigs fed casein was decreased, whereas the ileal output was not significantly affected. This could be attributed to increased uptake of bile acids from the cecum and/or colon, which may in part be related to the indirectly observed decreased formation of secondary bile acids. Postprandial serum concentrations of insulin and glucose were temporarily increased in pigs fed casein, whereas those of triglycerides were decreased. We suggest that the decreased excretion of cholesterol and bile acids is the major determinant of casein-induced hypercholesterolemia in swine. PMID- 2187961 TI - Does the mean corpuscular volume help physicians evaluate hospitalized patients with anemia? AB - The authors analyzed the value of using mean corpuscular volume (MCV) as a guide for selecting tests for further evaluation of anemia in hospitalized patients. Of the 2,082 patients with anemia admitted to the medical service of a teaching hospital over one year, 655 (31%) had further diagnostic tests to evaluate the cause of the anemia. Within this group of 655 patients, 399 (61%) had normal MCVs. Over half the patients with abnormal serum vitamin B12, folate, or ferritin levels, or with low serum iron (Fe) levels with elevated total iron-binding capacity (TIBC), did not have the MCVs expected according to the classification of anemia proposed by Wintrobe. Furthermore, 5% of patients with evidence of iron deficiency had high MCVs, and about 12% of patients with decreased vitamin B12 levels had low MCVs. The MCV was quite specific in identifying patients who had low ferritin levels: specificity was 83%; however, sensitivity was only 48%. The MCV was also specific (88%) for identifying patients who had low Fe with elevated TIBC; however, sensitivity was only 43%. The MCV was poor in identifying patients with abnormalities of serum vitamin B12 and folate levels. In this study the MCV did not provide sufficient diagnostic accuracy to be a useful criterion for the selection of more definitive tests in the evaluation of anemia in hospitalized patients. PMID- 2187964 TI - Odontogenic keratocysts: clinicopathologic study of 87 cases. AB - The clinical and histologic features of 87 cases of odontogenic keratocysts were reviewed. Males were affected more frequently than females. All age groups were affected, with a predilection for the fifth and sixth decades. The molar-angle ramus area of the mandible was the most common location (29.8%). In 7 cases (8.8%), the cysts were part of the basal cell nevus syndrome. Recurrences were observed in 9 cases (10.4%). The cysts were lined by a thin, regular, stratified squamous, parakeratinized epithelium without rete ridges. Orthokeratin was observed in 24.14% of the cases. Mitotic figures were observed in approximately 50% of the cases. Separation of lining epithelium from underlying connective tissue was observed in 82.7%, with subepithelial hyalinization in 75.8% of the cases. Inflammation was observed in 72.4%, cholesterol clefts were observed in 11.5%, and Rushton hyaline bodies in 4.6% of the cases. Dental lamina rests were observed in 32.2% and satellite cysts in 20.7%. Dystrophic calcifications were found in 36.8%. Ameloblastomatous proliferation was observed in 2 cases. PMID- 2187963 TI - Zidovudine prophylaxis following exposure to human immunodeficiency virus. PMID- 2187965 TI - The development of the dual-degree controversy in oral and maxillofacial surgery. PMID- 2187966 TI - An unusual case of intraparotid foreign body. AB - Foreign bodies in salivary glands are an unusual event; foreign bodies simulating parotid tumors are an exceptional finding. A posttraumatic case of intraparotid foreign body and a brief literature review are presented. PMID- 2187962 TI - Medical complications of intravenous drug use. PMID- 2187967 TI - Atypical histiocytic granuloma: report of a case. PMID- 2187968 TI - Calcifying odontogenic cyst: case report and review of literature. AB - A case of calcifying odontogenic cyst is presented. An analysis of the previously reported cases indicates the variable clinical, radiographic and histopathologic features of the lesion. PMID- 2187969 TI - Recurrent temporomandibular joint subluxation and facial ecchymosis leading to diagnosis of Ehlers-Danlos syndrome: report of surgical management and review of the literature. AB - This article reports a patient with Ehlers-Danlos syndrome for whom the syndrome was diagnosed as a result of her TMJ complaints. The surgical management of the patient's joint laxity is discussed, and a review of the syndrome's biochemical basis, clinical features, and importance to the surgeon is presented. PMID- 2187970 TI - A clinical evaluation of conventional bridgework. AB - The present study evaluated the incidence and causes of failure of conventional bridgework provided in the Prince Philip Dental Hospital, Hong Kong. Any bridge that utilized resin-bonded (Maryland) retainers was excluded from this study. All patients with bridges fitted between 1981 and 1987 were recalled for review, and 143 patients attended, a response rate of 77%. A total of 169 bridges were examined, their mean length of service being 35 months. Thirty-five bridges were deemed to have failed. The most frequent cause was endodontic, followed by loss of retention, then persistent pain and sensitivity. Failures of endodontic origin affected mostly anterior bridges, which could be attributed to the over-sized pulp of anterior teeth and the amount of tooth reduction required for the ceramometal retainer. All of the bridges that failed because of endodontic problems had had ceramometal retainers. Taking posterior bridges alone, the failure rate was 4.4% per year. From the evidence of this study, the replacement of the maxillary canine with a cantilever bridge appears to be contra-indicated. PMID- 2187971 TI - Oral comfort in shortened dental arches. AB - In this study, the oral comfort was compared between subjects with shortened dental arches (SDA, n = 74), subjects with SDA and free-end removable partial dentures (SDA + RPD, n = 25) and subjects with complete dental arches (CDA, n = 72). Oral comfort was measured by (i) absence of pain or distress; (ii) chewing ability; (iii) appreciation of the appearance of the dentition. Additionally, the history of free-end RPD over a period of nearly 7 years was taken into consideration. On the whole, the results did not reveal any significant differences between the three groups with respect to pain or distress. Only 8% of the subjects with SDA reported impairment of chewing ability, and 11% had aesthetic complaints, due to missing posterior teeth in the upper jaw. Of the subjects with SDA + RPD, 20% had complaints about the RPD. In addition, the repeated necessity for repair or replacement of free-end RPD and the fact that some subjects (20%) stopped wearing the RPD during the observation period, confirm the poor performance of this dental provision. It is concluded that the oral comfort of subjects with SDA in this study is compromised to a small extent but remains on an acceptable level. Free-end RPDs do not appear to help oral comfort in these cases. PMID- 2187972 TI - Clinical performance of resin-bonded bridges: a 5-year prospective study. Part III: Failure characteristics and survival after rebonding. AB - A total of 203 resin-bonded bridges were inserted under controlled clinical conditions and evaluated over a period of 5 years. During the evaluation period there were 47 dislodgements and 30 pontic fractures. The majority of the failures were retreated successfully. Dislodgement was in most cases due to fracture at the resin/retainer interface. The small number of fractures at the resin/tooth interface indicate that the clinical procedures, as used in this study, were satisfactory. Dislodged and rebonded resin-bonded bridges had a lower retention than original bonded bridges, indicating that patients with a dislodged bridge are a risk group for the retention of rebonded bridges. However, possible factors that may be responsible for this higher risk could not be demonstrated. The bridges which were removed for repair of the pontics and rebonded showed an acceptable retention. There was no relationship between the failure characteristic and the retainer type or the cementation material used. PMID- 2187973 TI - Pharmacological evaluation of hydroxypropylcellulose-ethylcellulose microcapsules containing piretanide. AB - Hydroxypropylcellulose (HPC)-ethylcellulose (EC) microcapsules containing piretanide prepared by a solvent evaporation technique, were evaluated on pharmacokinetic, pharmacodynamic and pharmacological parameters in spontaneously hypertensive rats (SHR). HPC-EC10 (5:3) microcapsules showed sustained plasma piretanide levels and almost the same AUC (area under the curve) as compared with piretanide solution. Effect of treatment with the microcapsules (single oral administration per day in doses of 10 and 30 mg/kg) and the solution (double oral administration per day in doses of 5 and 15 mg/kg) was examined for 4 weeks on urine volume and urinary electrolytes excretion and blood pressure. The microcapsules and solution induced dose-dependent diuresis throughout the experimental period and a reduction in blood pressure from 2 weeks of the treatment. HPC-EC10 (5:3) microcapsules containing piretanide were satisfactory as a sustained-release preparation in the light of the anti hypertensive effect even at a half frequency of daily dosing of the solution. PMID- 2187974 TI - Quantitative exfoliative cytology of normal buccal mucosa: effect of smoking. AB - The effect of cigarette smoking on the oral mucosa was assessed through the application of quantitative cytomorphometric analysis to smears obtained from clinically normal buccal mucosa. The nuclear (NA) and cytoplasmic (CA) area of cells within each smear were measured using a Vids V semi-automatic image analysis system. Mean values for NA (smokers--78.74 microns 2, non-smokers--72.28 microns 2 and for CA (smokers--3273.9 microns 2, non-smokers--3098.96 microns 2) were obtained. A two-sample t-test revealed a significant elevation in NA for smokers, but no significant variation in CA between the two groups. These results would suggest that for normal buccal mucosa smoking does appear to influence cytomorphology. PMID- 2187975 TI - The diagnostic uses of saliva. AB - It is becoming increasingly apparent to investigators and clinicians in a variety of disciplines that saliva has many diagnostic uses and is especially valuable in the young, the old and infirm and in large scale screening and epidemiologic studies. The highly sensitive test procedures that are now commonplace makes it practical to quantitate, despite very low concentrations, a large number of hormones and drugs in saliva. Indeed, all steroids of diagnostic significance in routine clinical endocrinology can now be readily measured in saliva. Drug monitoring can include abusive as well as therapeutic agents. The concordance between anti HIV antibodies in saliva and serum has stimulated application to various other antiviral antibodies as well as to viral antigens per se. Saliva has found use as a diagnostic aid in an increasing number of clinical situations and in systemic diseases that can affect salivary gland function and composition such as Sjogren's syndrome, cystic fibrosis and diseases of the adrenal cortex. The list keeps growing. PMID- 2187976 TI - Quantification of plasma cells in labial salivary glands: increased expression of IgM in Sjogren's syndrome. AB - Plasma cells expressing IgG, IgA and IgM were quantified in labial salivary glands from patients with Sjogren's syndrome (SS) and compared with glands showing non-specific inflammatory changes and normal controls. In all glands the predominant isotype was IgA but in SS there was a significant increase in both the number and proportions of IgG and IgM positive cells (P less than 0.002). In particular, all SS cases contained greater than 10% IgM positive cells (mean = 26.8 +/- 15.5). The results suggest that accumulation of IgM positive plasma cells may be a specific finding in SS and support the concept that the glandular lesions may be a site of B-cell clonal expansion. Since most B-cell hyperproliferative states in SS, including lymphoma, are associated with synthesis of IgM simple quantification of plasma cells may have important diagnostic and prognostic significance. PMID- 2187978 TI - Psychological characteristics of over- and undercontrolled violent offenders. AB - Megargee (1966, 1973) has predicted a number of concomitant social, behavioral, and psychological differences between chronically undercontrolled and chronically overcontrolled violent individuals. Attempts to validate his theory, however, have resulted in seriously inconsistent findings, possibly because of the use of a measure to classify violent subjects that is of seemingly dubious validity--the Overcontrolled Hostility (OH) Scale (Megargee, Cook, & Mendelsohn, 1967). The present study used a different strategy--the classification of subjects by expert raters on the basis of extensive case history information--to compare overcontrolled violent, undercontrolled violent, and nonviolent criminal offenders on a number of psychometric measures (16PF, Hostility and Direction of Hostility Questionnaire, Picture Situation Test, and the OH Scale). The findings were broadly consistent with predictions derived from Megargee's theory. Contrary to expectation, however, the nonviolent group did not obtain scores intermediate to the other two groups, but was statistically indistinguishable from the undercontrolled group, leaving a question as to the appropriateness of conceptualizing the typology in terms of over- and undercontrol of hostility and suggesting the necessity for some revision of the theory. PMID- 2187977 TI - Experimental oral candidosis in the mouse: microbiologic and histologic aspects. AB - A model of oral candidosis was developed in order to investigate histologic and microbiologic aspects of this host-parasite interaction under controlled experimental conditions. Normal adult CD-1 mice were inoculated by the topical application of 10(8) Candida albicans blastospores, and oral colonization was monitored by the quantitative culturing of saliva samples and of digested oral mucosa. Tissue sections of the mucosa were examined in a kinetic study ranging from 2 h to 13 days postinoculation. We report here that oral colonization by C. albicans can be induced in normal adult mice without the use of any compromising agent and that the animals recover from this mucosal infection following a reproducible pattern. Temporal analysis of the oral histopathology showed that distinct patterns of inflammation are associated with particular stages in the development of the infectious foci. This experimental model offers a means of further investigating the host-parasite interactions involved in the onset and development of oral candidosis. PMID- 2187979 TI - Transcendence and psychological health: studies with long-term participants of the transcendental meditation and TM-Sidhi program. AB - We investigated the nature of the relationship between experiences of transcendental consciousness and psychological health. In Study 1, three groups with different levels of experience in transcendental meditation (TM) and in the TM-Sidhi program (techniques that have been shown to produce experiences of transcendental consciousness) were studied, using the self-investigation method of Hermans (1976). We employed blind interviewers and raters with various attitudes toward TM to minimize the possible impact of a variety of artifacts. Cross-sectionally, experience with TM and the TM-Sidhi program was positively related to a general measure of psychological health (p = .002); longitudinally, the meditating groups improved more than the control group on the psychological health measure (p less than .03). In Study 2, two contrast groups of long-term participants were similar on several confounding variables but differed on physiological indicators of experiences of transcendental consciousness. The groups with the positive physiological indicators showed a trend toward higher scores on the psychological health factor (p = .092), indicating that psychological health may be developed through the systematic cultivation of transcendental meditation and the TM-Sidhi program. PMID- 2187980 TI - The Barnum effect in a computerized Rorschach interpretation system. AB - Twelve psychiatric outpatients were administered the Rorschach test, and results were interpreted using the Exner (1983, 1986) Report for the Comprehensive System computer-based test interpretation (CBTI) program. Four psychiatrists made accuracy ratings for both real and bogus reports for each of their patients. Data were analyzed using two-way analyses of covariance (ANCOVAs), where report type was a repeated main effect, psychiatrist was a random main effect, and the number of statements in the report was the covariate. Results indicated that this CBTI provided only 5% discriminating power for any one patient, with 60% of the interpretive statements merely describing typical characteristics of the outpatient population. No significant psychiatrist, interaction, or covariate effects were encountered. PMID- 2187981 TI - Neuropsychophysiology during relaxation in generalized, universal 'allergic' reactivity to the environment: a comparison study. AB - Comparisons were made among a group of patients presenting with universal 'allergic' intolerance to environmental chemicals (universal reactor, n = 58), a group of control subjects without psychologic symptoms (control, n = 55) and a group of outpatients from a psychology practice (psychologic, n = 89) on neuropsychophysiological measures during relaxation. The measures were electroencephalographic (EEG) spectral category for frequencies below 15 Hz, EEG beta activity, scalp electromyography (EMG), peripheral temperature (TEMP), and skin resistance level (SRL). The distributions of subjects in each group across eight EEG spectral categories were significantly different, with the distribution for universal reactors the same as that of the psychologic patients (p = 0.22), and both different from the distribution of controls (p less than 0.001). High levels of EEG beta activity were observed in more universal reactors and psychologic patients than in controls (p = 0.04). High levels of EMG scalp activity were observed in a greater number of universal reactors than in subjects in the other two groups (p less than 0.001). The three groups did not differ in TEMP and SRL. Implications of neuropsychophysiologic stress profiling for the diagnosis and treatment of psychosomatic illness are discussed. PMID- 2187982 TI - Psychic effects of physical training and relaxation therapy after myocardial infarction. AB - The psychological impact of exercise training and relaxation therapy was investigated in 156 myocardial infarction patients. They were randomly assigned to either exercise plus relaxation and breathing therapy (Treatment A: n = 76) or exercise training only (Treatment B: n = 80). Patients in Treatment A improved on three out of eight psychological measurements (anxiety, well-being, feelings of invalidity). No change was demonstrable in Treatment B. The difference between the treatments was significant for wellbeing (p less than 0.005). Physical outcome, measured by exercise testing was positive in about half of the patients (Treatment A: 55%, Treatment B: 46%). A negative outcome occurred less in Treatment A (p less than 0.05). Training success was not associated with psychic benefit. The association differed for the two treatments. It was concluded that exercise training was effective for some but not for all cardiac patients, and that a psychic effect of exercise could not be demonstrated. Relaxation therapy enhanced physical and psychic outcome of rehabilitation. PMID- 2187983 TI - The role of viruses in feline lower urinary tract disease. AB - Viruses have been implicated as causative agents in the etiopathogenesis of some forms of feline lower urinary tract disease (LUTD). This hypothesis was supported by isolation of feline calicivirus, bovine herpesvirus 4 (strain FeCAHV), and feline syncytia-forming virus from cats with naturally occurring LUTD, and by experimental studies of induced viral urinary tract infection. Results of early clinical studies yielded contradictory results concerning the role of viruses in feline LUTD. However, recent detection of bovine herpesvirus 4 antibodies in feline serum samples and discovery of calicivirus-like particles in crystalline/matrix urethral plugs obtained from cats with naturally occurring LUTD, suggests the need to reexamine the etiopathologic role of viruses using contemporary methods of virus identification and localization. PMID- 2187985 TI - Responses to illness--implications for the clinician. PMID- 2187984 TI - Milrinone. A clinical trial in 29 dogs with moderate to severe congestive heart failure. AB - Milrinone, a positive inotropic drug with vasodilating properties, was administered at doses of 0.5 to 1 mg/kg orally twice daily to 29 dogs with moderate to severe congestive heart failure (CHF). Significant echocardiographic improvement in ventricular systolic function was observed after 3 days of administration of milrinone and at the patients' last echocardiographic observation (day 21 in 25 subjects, day 7 in 2 subjects, and day 3 in 2 subjects). Echocardiographic shortening fraction at the initial measurement had a median increase of 6.14% (P less than 0.001), and for the last observation a 2.83% increase (P less than 0.005). Most patients also showed improvement in their clinical signs as assessed by the veterinarian (72%) and by owner's evaluation (81%). No consistent problem or adverse reaction to milrinone was observed, except for a small number of clinically manageable ventricular dysrhythmias. Milrinone appears in this trial to be effective for the treatment of advanced CHF in dogs. PMID- 2187987 TI - In vitro fertilization--some comparative aspects. PMID- 2187986 TI - Research on the human conceptus and its regulation in Britain today. PMID- 2187988 TI - The management of psychiatric disorders in the community. The research magnificent. PMID- 2187989 TI - Eating disorders in general practice. PMID- 2187990 TI - The influence of John Hunter's inoculation practice on Edward Jenner's discovery of vaccination against smallpox. PMID- 2187991 TI - Henry Vaughan and his MD. PMID- 2187992 TI - Proteases, dermal proliferation, keratinization and calcium. PMID- 2187993 TI - Potassium channel modulators: scientific applications and therapeutic promise. PMID- 2187994 TI - Potent, low molecular weight renin inhibitors containing a C-terminal heterocycle: hydrogen bonding at the active site. AB - A series of low-nanomolar renin inhibitors containing novel C-terminal heterocycles has been designed by formally cyclizing the C-terminus of a glycol based inhibitor to the second hydroxyl. Molecular modeling suggests that the heterocyclic oxygen hydrogen bonds as an acceptor to the flap region of renin and that the second hydroxyl in the glycol-based inhibitors behaves similarly. PMID- 2187995 TI - O'-(epoxyalkyl)tyrosines and (epoxyalkyl)phenylalanine as irreversible inactivators of serine proteases: synthesis and inhibition mechanism. AB - A series of O'-(epoxyalkyl)tyrosines and a carboxy terminal (epoxyalkyl)tyrosine and -phenylalanine were synthesized as potential serine protease inhibitors. N Acetyl derivatives showed irreversible inactivation vis-a-vis subtilisin, while the N-benzoyl ones were specific toward chymotrypsin. The most potent inactivation of chymotrypsin was achieved by a O'-(3,4-epoxybutyl)-L-tyrosine derivative. The inactivation was shown to be stereospecific since a D derivative led to no irreversible inactivation. Placement of the epoxyalkyl group at the carboxy terminus led to potent rapid inactivation. Under these conditions some of the activity was later recovered. The two classes of inactivators (O'-epoxyalkyl and carboxy-epoxyalkyl) appear to operate by different mechanisms. Most importantly, it was found that irreversible inactivation by O'-(epoxyalkyl)-L tyrosine only resulted if the carboxy terminus was a substrate (i.e. a compound with free carboxy terminus did not lead to inactivation). The ultimate activity kinetic assay (Daniels, S. B.; et al. J. Biol. Chem. 1983, 258, 15046-15053.) indicated that the epoxyalkyl group on the phenolic oxygen had an optimal length of four carbons with respect to the turnover ratio (the ratio of molecules undergoing turnover compared to those that inactivate the enzyme) for chymotrypsin. A different kinetic assay (Ashani, Y.; Wins, P.; Wilson, I. B. Biochim. Biophys. Acta 1972, 284, 427-434.) demonstrated that substratelike turnover was proceeding at considerably slower rates than for the corresponding true substrates and with rate-limiting deacylation of the acyl-enzyme. Amino acid analysis subsequent to acid hydrolysis demonstrated that Met had been selectively alkylated by the O'-(epoxyalkyl)tyrosine derivative. By contrast, alpha chymotrypsin inactivated with N-benzoyl-L-Phe-2,3-epoxypropyl ester then subjected to amino acid analysis showed no change in the content of any amino acid that would serve as a potential nucleophile to the inhibitor. Yet, the L-Phe content increased, indicating that a covalent bond had been formed between the inhibitor and the enzyme. Either the bond between the inhibitor and the enzyme did not withstand the hydrolytic conditions and/or there was less than 10% decrease in the amino acids with nucleophilic side chains upon inactivation. Finally, two tripeptides containing O'-(epoxyalkyl)-L-tryosines were synthesized [N-(tert-butoxycarbonyl)-L-alanyl-L-alanyl-O'-(2,3-epoxypropyl)-L-tyrosi ne ethyl ester and N-(trifluoroacetyl)-L-valyl-O'-(2,3-epoxypropyl)-L-tyrosyl-L-valine methyl ester] as potential elastase inhibitors and were found to reversibly and competitively inhibit porcine pancreatic elastase. PMID- 2187996 TI - The use of functional analyses to test causes of self-injurious behaviour: rationale, current status and future directions. AB - Self-injurious behaviour (SIB) is a relatively common phenomenon among severely retarded persons and involves various repetitious behaviours resulting in tissue damage. Perhaps because of the damage it does, the behaviour has generated a considerable amount of applied research and discussion, and much of this research has involved attempts to reduce SIB through the manipulation of antecedents or consequences. The purpose of this paper was to determine the extent to which those conducting this research used a functional analysis of SIB to determine why the behaviour was occurring and subsequently matched treatment to one of these reasons. Results showed that only a small proportion of the studies reported analyses that would allow the experimenter to determine reasons for the self injurious behaviour. The discussion centres on why functional analyses are not conducted in ways that would lend treatment to be based on hypotheses of why SIB occurs. PMID- 2187997 TI - Crystallization and preliminary X-ray diffraction analysis of catalase HPII from Escherichia coli. AB - Green crystals of the hexameric catalase HPII from Escherichia coli have been obtained by the hanging-drop method. The crystals belong to the monoclinic space group P2 with a = 123 A, b = 132 A, c = 93 A, beta = 112.5 degrees. There are three subunits in the asymmetric unit. The crystals diffract at least to 3.2 A resolution and are suitable for further X-ray diffraction studies. PMID- 2187998 TI - DNA sequence analysis of mutations induced by N-2-acetylamino-7-iodofluorene in plasmid pBR322 in Escherichia coli. AB - The spectrum of mutations induced by N-2-acetylamino-7-iodofluorene (AAIF) was analyzed in a forward mutation system based on mutagenesis directed to a small restriction fragment in the tetracycline resistance gene of plasmid pBR322. AAIF was found to induce frameshift mutations and base-pair substitutions at approximately equal frequencies. The frameshift mutations were mostly deletions of single base-pairs, but -2 frameshifts and +1 frameshifts were also detected. With one exception, the substitutions were transversions initiated at a G.C base pair. Both frameshift mutations and transversions occurred preferentially at sites of repetitive guanine residues. Although AAIF and the related aromatic amines N-2-acetylaminofluorene (AAF) and N-2-aminofluorene (AF) all bind to the C 8 position of guanine, they have different effects on DNA conformation, and these differences are reflected in their mutation spectra. Previous studies have provided evidence that AAF adducts can trigger a B to Z conformational change in alternating GC sequences or displacement of the guanine by the fluorene ring in other sequences; the principal result is two classes of frameshift mutations. AF, whose DNA interaction involves outside binding rather than insertion and denaturation, primarily induces base-pair substitutions. AAIF adducts are chemically similar to AAF adducts, but the iodo group apparently hinders insertion of the fluorene ring into DNA. Consistent with this model, the mutation spectrum of AAIF combines properties of the mutation spectra of both AAF and AF. PMID- 2187999 TI - Statistical designs for investigating several interventions in the same study: methods for cancer prevention trials. PMID- 2188000 TI - Samuel D. Gross: pioneer academic trauma surgeon of 19th century America. AB - It is appropriate on the 50th anniversary of the American Association for the Surgery of Trauma to recall the most influential trauma surgeon in 19th century America: Samuel D. Gross. Gross was an innovative surgeon whose 50-year career as a surgeon caring for injured patients encompassed orthopedics, thoracic surgery, abdominal surgery, and ophthalmology. The dominant influence of Gross over contemporary surgical doctrine was a consequence of his prolific scholarship which included six superbly written texts that passed through a combined total of 15 editions. Gross was a teacher, occupying for 42 years Chairs of Surgery at three medical schools. Gross wore the mantle of political leadership, founding medical societies that continue today as forums for the presentation and review of new treatments for injured patients. Modern academic trauma surgeons could do no better than to emulate the career of Samuel David Gross, the Patriarch of American trauma surgeons. PMID- 2188001 TI - Asymptomatic occult cervical spine fracture: case report and review of the literature. AB - Lack of case documentation has led to controversy over the existence of asymptomatic occult cervical spine injury. We report a case of an elderly patient involved in a motor vehicle accident who sustained an asymptomatic occult cervical spine injury, and review the literature with regard to this controversial injury. PMID- 2188002 TI - Neuro-Behcet's disease: report of three cases with a review of the literature. AB - We report three cases of neuro-Behcet's disease, including one woman and two men (age range 52-56 years), who displayed symptoms of high fever, headache and confusion. The EEG showed generalized slowing in two cases, and periodic lateralized epileptiform discharges in one. Brain CT scans from two patients revealed cortical atrophy with multiple low density areas in one case, and focal contrast enhancement in the other. The CSF study revealed pleocytosis in all cases, but only one showed lymphophagocytosis. All of the patients responded dramatically to steroid therapy, although administration of the drug was somewhat delayed in two cases, during which initial management was aimed at the CNS infection of bacterial origin. Recurrent attacks of confusion or mental dullness were found in two patients, and high cortical dysfunction persisted on follow-up for some time. The clinical manifestations, laboratory findings, and neuroradiological features of neuro-Behcet's disease in the reported cases are reviewed. PMID- 2188003 TI - Functional assessment of uteroplacental and fetal circulations by means of color Doppler ultrasonography. AB - A study was made in order to assess whether the combined use of color flow mapping and conventional pulsed Doppler could improve the accuracy of blood flow velocity waveform analysis in fetal and placental circulations. Fifty patients were studied at 18 to 20 or 26 to 28 weeks of gestation by two trained investigators by means of either conventional Doppler or conventional Doppler plus color flow mapping. Recordings were performed at the level of the uterine arteries, umbilical artery, descending aorta, and internal carotid artery. The experimental procedure was repeated the following day with the patients undergoing the alternate technique of recording. In all the vascular districts investigated, color flow mapping allowed us to obtain a higher number of reliable recordings, to shorten the observation time, and to reduce the intra- and interobserver coefficient of variations. PMID- 2188004 TI - Color Doppler artifact in anechoic regions. AB - For color Doppler imaging, several types of signal processing are employed in order to produce acceptable images of blood flow in blood vessels while suppressing color in moving solid tissue. The processing can produce an artifact in which color may arise from noise or from tissue motion and fill anechoic regions preferentially. This artifact may complicate the differentiation of areas with blood flow from anechoic regions without flow. By using four different color Doppler ultrasound units to image a tissue-equivalent phantom containing anechoic cylinders, artifactual color resulted when gain was raised sufficiently. This color was concentrated in anechoic regions of a gray-scale image that did not contain flow. In two instruments, this artifact was only observed when the transducer was vibrated, simulating tissue motion. In these instruments, the identification of low-frequency, high-amplitude Doppler signals is used to locate moving solid tissue and so suppress color in these regions. In the other two instruments, the presence of echoes within the image suppressed the assignment of color. With both types of processing, color may appear artifactually in echo-free regions without flow, such as fluid collections. Presence or absence of flow should be confirmed by Doppler spectral analysis. An understanding of the origin and appearance of artifactual color can prevent its occurrence from detracting from the usefulness of color Doppler imaging. PMID- 2188005 TI - Internal jugular venous flow measurement by means of a duplex scanner. AB - Using a special probe holder, cross-sectional area and time-averaged mean spatial velocity of the internal jugular vein were measured by means of a duplex scanner and multiplied to calculate volume flow. In a cohort of 100 subjects ages 21 to 70 years, average right plus left flow was 740 +/- 209 mL/min. Flow was 8.7% lower in females than in males. Normalization of flow to 100 g brain tissue by dividing it through the mean sex specific brain weight resulted in no significant sex difference. Within the age range investigated, there was no decrease of flow with age. PMID- 2188006 TI - Duplex ultrasound analysis of operated carotid arteries in baboons. AB - Duplex ultrasound analysis, which combines high-resolution B-mode imaging and Doppler spectral flow analysis, was used to examine 3 to 4 mm in diameter normal [n = 24] and mechanically manipulated baboon carotid arteries (endarterectomies [n = 10], construction of interposition vascular grafts [n = 10], and placement of endovascular stents within interposition grafts [n = 4]). Patency or occlusion was definitively confirmed by direct visualization and palpation during surgical exploration at defined intervals or by postmortem histologic examination. Duplex examination accurately demonstrated postoperative hemodynamic changes and with only one exception correctly identified patency and occlusion. We conclude that this technique is superior to more invasive methods for verification of the outcome of operations on small arteries in experimental animals. PMID- 2188007 TI - Improving the outcome of cervical cerclage by sonographic follow-up. AB - A total of 39 patients with the diagnosis of cervical incompetence were followed up with cervical sonography after placement of prophylactic McDonald cerclage. During the first year of study, 3 out of 12 patients treated with prophylactic cerclage demonstrated funneling of the internal cervical os when examined with cervical sonography; all 3 had premature deliveries. During the last 3 years of the study, 8 of 27 patients treated with prophylactic cerclage demonstrated funneling. With active intervention, neonatal survival improved to 100%. Sonography aids in the management of patients with cervical incompetence and improves outcome even after placement of cervical cerclage. PMID- 2188008 TI - Serial adrenal ultrasonography in normal neonates. AB - Six serial ultrasound scans were performed on each of 12 healthy term babies on days 1, 3, 5, 11, 21, and 42 of extrauterine life in order to determine normal neonatal values for various adrenal parameters. Measurements were made of transverse and anteroposterior diameters, of circumference and area in the transverse plane, and of longitudinal length of the adrenals and kidneys. There was a significant decrease in all adrenal parameters of 22%, 25%, 25%, 44%, and 34%, respectively, between days 1 and 5 (p less than .002) and of 46%, 39%, 46%, 67%, and 55%, respectively, between days 1 and 42 (p less than .00005), whereas the kidneys increased in size over the same period. PMID- 2188010 TI - The value of ultrasound for the diagnosis of malignant hyperthermia. AB - A highly feared complication of anesthesia is malignant hyperthermia (MH). In vivo identification of MH is achieved sonographically. Transducers of 7.5 and 5 MHz were used for transverse cuts of the upper and lower leg. Sonographic changes were found in 22 out of 33 subjects from 12 families affected by MH, including several positive subjects not previously known to be subject to MH. The ultrasound image reveals increased parenchymal echogenicity, with obscuring of intramuscular septum and fascia. Myosonography allows noninvasive screening of family members of subjects with known MH; potentially dangerous challenge testing or biopsy may be reserved for specific indications. PMID- 2188009 TI - Incidence of portal vein thrombosis complicating liver metastasis as detected by duplex ultrasound. AB - In a prospective study of 100 patients with liver metastasis using real-time ultrasound, 8 patients (8%) were found to have portal vein thrombosis (PVT). Sixty seven of these patients, which included all with PVT, also underwent duplex examination. Pulsed Doppler showed absent flow in 4 of 8 patients, indicating complete obstruction. The other 4 showed different degrees of flow suggesting incomplete obstruction or collateral formation. We conclude that PVT complicating liver metastasis is not a rare finding. PMID- 2188011 TI - Umbilical cord hemangioma. Prenatal identification and review of the literature. PMID- 2188012 TI - Transitional cell carcinoma of a simple ureterocele. A specific sonographic appearance. PMID- 2188013 TI - Prenatal diagnosis of schizencephaly. PMID- 2188014 TI - Urological aspects of renal transplantation. PMID- 2188015 TI - High resolution ultrasonography and pulsed wave Doppler for detection of corporovenous incompetence in erectile dysfunction. AB - Cavernosometry and cavernosography have been the primary modalities available for detection and mapping of corporovenous incompetence in patients with erectile dysfunction. These procedures are expensive, time-consuming and associated with some morbidity, prompting us to study a less invasive method, high resolution ultrasonography and pulsed wave Doppler ultrasound. We evaluated 13 patients with nonendocrinological, nonneurological erectile dysfunction by high resolution and Doppler ultrasound for flow in the dorsal and cavernosal veins after intracorporeal papaverine. All patients had a nonrigid response to papaverine and a mean maximum cavernous arterial systolic velocity of greater than 25 cm. per second. The 13 patients were subsequently studied by dynamic cavernosometry and cavernosography, which revealed evidence of venous incompetence (12 with dorsal venous leaks and 11 with cavernous venous leaks). Only 5 of the 12 patients with dorsal venous incompetence had flow detected in the dorsal vein by ultrasound and Doppler studies. High resolution and Doppler ultrasound was unable to detect leakage in the cavernous veins. Among the 2 groups of patients with dorsal venous leaks (those with and without flow detectable by Doppler ultrasound) there was no significant difference in mean cavernous artery diameter or mean cavernous arterial maximum velocity. Similarly, there was no significant difference between the 2 groups in induction, maintenance or initial decompression rates on cavernosometry. We conclude that high resolution and Doppler ultrasound cannot replace dynamic cavernosometry and cavernosography as the diagnostic modality for venous incompetence. PMID- 2188016 TI - Correlation between penile angiography and duplex scanning of cavernous arteries in impotent men. AB - During the diagnostic evaluation of patients with vasculogenic impotence duplex scanning has been proposed as a reliable noninvasive method to evaluate the cavernous arteries. However, the sensitivity and specificity of this test have never been elucidated. To provide insight into the clinical value of this test 25 men who presented with impotence and failed to respond to 60 mg. intracavernous papaverine were evaluated with duplex scanning and the results of this modality were compared to penile angiography. The cavernous arteries were considered normal by duplex scanning if the artery demonstrated either a 60% or greater increase in diameter and/or a peak flow velocity of greater than 25 cm. per second 5 minutes after papaverine injection. Penile angiography was considered normal if both cavernous arteries were visualized and appeared to be normal radiographically (after intracorporeal papaverine). In the 25 patients studied there was no significant difference in peak flow velocity between patients with normal or abnormal cavernous arteries by angiography. In addition, arterial dilatation (more than 60%) after papaverine injection did not correlate with the results of the angiogram. These data demonstrate that duplex scanning of the cavernous arteries does not correlate well with what is observed by penile angiography in a selected population of men with vasculogenic erectile dysfunction. Since penile angiography itself has limitations in the evaluation of the penile arteries, the reliability of duplex scanning to identify cavernous artery dysfunction needs additional confirmation. PMID- 2188017 TI - Upper urinary tract filling defects: flexible ureteroscopic diagnosis. AB - There were 62 patients referred to our institution for evaluation of upper urinary tract filling defects. These patients had undergone any of several diagnostic evaluations, including computerized tomography, B-mode ultrasound scanning and urinary cytology studies with or without upper tract brush biopsy. In all cases a conclusive diagnosis could not be formulated. With the use of flexible ureteropyeloscopy complete evaluations of the upper tract lesions were performed. The upper tract endoscopic procedure provided the diagnosis in all patients, as well as allowed for therapeutic intervention in 19. There was no significant morbidity associated with any procedure. We advocate the continued development of flexible ureteropyeloscopic instrumentation and procedures. We suggest the inclusion of ureteropyeloscopy with tissue sampling of neoplasms in the evaluation of all upper urinary tract lesions, except when diagnostic ultrasound correlates the characteristics and position of the lesion as calculous disease. PMID- 2188018 TI - Scrotal surgery: a reliable method for the prevention of postoperative hematoma and edema. AB - Hematoma and edema are the most frequently encountered complications of scrotal surgery. Unless properly managed, both conditions can lead to significant morbidity for the patient. A simple method is described that effectively and reliably eliminates these untoward effects for men undergoing orchiectomy, hydrocelectomy, spermatocelectomy or epididymectomy. PMID- 2188020 TI - Intraoperative ultrasonographically guided biopsy in testicular sarcoidosis: a case report. AB - We present a case of sarcoidosis with involvement of a solitary testis that was discovered incidentally on an ultrasonogram of the scrotum. This appears to be case 8 of sarcoidosis with genitourinary involvement limited to the testis. We believe it is the second report of intraoperative ultrasonography used to locate and perform a biopsy of impalpable testicular lesions. We consider this technique to be useful in instances of solitary gonads or in cases of bilateral lesions. PMID- 2188019 TI - Local tissue reaction to the subureteral injection of glutaraldehyde cross-linked bovine collagen in humans. AB - Although the technique of subureteral injection has been widely accepted as an alternative to reimplantation in the treatment of vesicoureteral reflux, the choice of the material to be used is controversial. We have used glutaraldehyde cross-linked bovine collagen to correct vesicoureteral reflux within the context of a Food and Drug Administration approved investigational study. We report the local tissue reaction to the implanted collagen in 7 patients who underwent reimplantation 3 to 19 months after failed endoscopic therapy. Glutaraldehyde cross-linked bovine collagen engendered a minimal localized inflammatory reaction without causing granuloma formation. Subsequent reimplantation was not hindered by the presence of the implant materials. PMID- 2188021 TI - Embryonal rhabdomyosarcoma arising in a mature teratoma of the testis: a case report. AB - We report a case of embryonal rhabdomyosarcoma present in the primary excision of an intratesticular purely mature teratoma. Testicular mature and immature teratomas are usually associated with other germ cell tumors. Nongerminal malignancies that tend to occur in gonadal and extragonadal teratomas are often epithelial. Sarcomas of all types are less frequent but embryonal rhabdomyosarcomas are encountered predominantly. This sarcomatous element can be present in the primary excision or it can appear after chemotherapy in the metastases. Usually, prognosis is dependent on the degree of aggressiveness of the sarcomatous component. A review of the literature reveals that it is unusual for an embryonal rhabdomyosarcoma to develop on purely mature teratoma. We report a case in the testicle. During followup metastases arise rapidly from the purely embryonal rhabdomyosarcomatous component. The accurate diagnosis of this unusual sarcomatous component is of paramount importance because of the implications for therapy. PMID- 2188022 TI - Fully implanted left ventricular assist device may enter clinical trials early in 1991. PMID- 2188023 TI - Enhancing the outcomes of low-birth-weight, premature infants. A multisite, randomized trial. The Infant Health and Development Program. AB - The Infant Health and Development Program is an eight-site clinical trial designed to evaluate the efficacy of a comprehensive early intervention in reducing the developmental and health problems of low-birth-weight (less than or equal to 2500 g) premature (less than or equal to 37 weeks) infants. Nine hundred eighty-five infants, stratified by site and weight (less than or equal to 2000 g or 2001 to 2500 g), were randomly assigned to receive an educational curriculum focused on child development, as well as family support and pediatric follow-up, or only pediatric follow-up. At corrected age 36 months, the intervention group had significantly higher mean IQ scores than the follow-up group (mean difference in the heavier group was 13.2 and in the lighter group 6.6), significantly fewer maternally reported behavior problems, and a small, but statistically significant, increase in maternally reported minor illnesses for the lighter birth-weight group only, with no difference in serious health conditions. PMID- 2188024 TI - Substance abuse and adolescent suicidal behavior. AB - Evidence suggests a significant association between use of psychoactive substances among adolescents and suicidal behavior among adolescents during the past two decades. Accumulating evidence, although not unanimous, supports the hypothesis of psychoactive substance abuse among adolescents as a risk factor for a range of suicidal behavior--ideation, attempted suicide, and completed suicide. With increasing rates of psychoactive substance abuse for the adolescent population during the past 20 years, this appears to be an increasingly important factor. It is not known if the association is causal. Psychoactive substance abuse appears to be associated with a greater frequency and repetitiveness of suicide attempts, more medically lethal attempts, a measured seriousness of intention, and greater suicidal ideation. Additional data support a specific association between alcohol intoxication and suicide by firearms among adolescents. Adolescents who abuse psychoactive substances, particularly those with any type of depressive disorder, appear to be at higher risk for suicidal behavior and may need appropriate psychiatric treatment. PMID- 2188025 TI - Salivary peptide P-C modulates both insulin and glucagon release from isolated perfused rat pancreas. AB - The effect of salivary peptide P-C, saliva-derived peptide on glucose-induced insulin release was studied using perfused rat pancreas. Salivary peptide P-C (194 nM) remarkably potentiated glucose (8.3 and 16.7 mM)-induced insulin release, whereas the same concentration suppressed arginine (10 mM)-induced glucagon release. Both effects of salivary peptide P-C occurred in a concentration-dependent manner. These findings suggest that salivary peptide P-C may modulate both the levels of insulin and glucagon in vivo. PMID- 2188026 TI - Effects of WEB 1881 FU, a novel nootropic, on cholinergic and adrenergic receptors in the rat brain: action on M1-muscarinic receptors. AB - Effects of 4-aminomethyl-1-benzylpyrrolidin-2-one-hemifumarate (WEB 1881 FU), a novel pyrrolidinone nootropic, on acetylcholine (ACh) receptors and adrenoceptors were investigated using crude membranes of the rat brain. The affinity order of WEB 1881 FU was: M1-muscarinic (m) ACh receptor greater than M2-mACh receptor greater than alpha 2-adrenoceptor greater than beta-adrenoceptor greater than alpha 1-adrenoceptor greater than nicotinic ACh receptor. The WEB 1881 FU competition curve for [3H]pirenzepine binding in hippocampal membranes was rightward-shifted by GTP gamma S; such behavior was also observed in the case of oxotremorine but not with scopolamine. The effects of long-term administration of WEB 1881 FU (30 mg/kg/day, i.p.) for 21 days resulted in a significant decrease in the Bmax of [3H]quinuclidinyl benzilate binding in the cerebral cortex, hippocampus and striatum. In addition, the Bmax of [3H]pirenzepine binding to hippocampal and striatal membranes and that of [3H]AF-DX 116 binding to cerebellar membranes were significantly decreased as well. From these results, WEB 1881 FU seems to act on M1-mACh receptors, and its long-term administration probably induces the down-regulation of mACh receptors, mainly M1-mACh receptors in the hippocampus and striatum and M2-mACh receptors in the cerebellum. PMID- 2188028 TI - Heterotopic pancreas: a rare cause of bile duct dilatation--report of a case and review of the literature. AB - A case of a 77 year old woman with a heterotopic pancreas in the distal common bile duct is reported herein. The patient had no symptoms, but an ultrasound examination showed bile duct dilatation and subsequent endoscopic retrograde cholangiography demonstrated a spherical filling defect in the distal common bile duct. Under suspicion of a benign neoplasm in the common bile duct, resection of the common bile duct and hepaticojejunostomy using a Roux-en Y jejunal limb were successfully performed. Pathological examination revealed heterotopic pancreatic tissue in the distal common bile duct. This is only the ninth reported case of heterotopic pancreas occurring in the common bile duct or ampulla of Vater, and thus, a review of the literature is also given. PMID- 2188027 TI - Production of monoclonal antibody to human esophageal cancer cell line. AB - The immunization of Balb/C mice with esophageal cell line KYSE-50 established from poorly-differentiated esophageal squamous cell carcinoma, resulted in obtaining the monoclonal antibody KYMN-28-5. This monoclonal antibody is of the IgM class and recognizes a carbohydrate antigen contained in glycoproteins with molecular weights of 53 and 56K, and in neutral glycolipids extracted from teratomas. Tissue staining revealed that this monoclonal antibody reacts strongly with malignant tumors but only weakly, or not at all, with normal tissues, apart from squamous epithelial tissue. KYMN-28-5 is thus a useful tumor marker which will improved the accuracy of serological diagnosing squamous cell carcinoma when combined with the measurement of SCC antigen. PMID- 2188029 TI - Thymolipoma: a report of three cases. AB - Three cases of thymolipoma, seen in a 6 year old boy, a 34 year old woman and a 24 year old man are presented herein. The weight of each tumor was 1380 g, 670 g and 560 g respectively. The 2 male patients had no symptoms and the woman only complained of a fever. On CT scan the thymic tissue was recognized as islands of soft tissue density within a fatty mass, and T1 weighted MRI was helpful in demonstrating the predominant fatty nature of this tumor. Thus, our experience demonstrates that CT and MRI are valuable for establishing a diagnosis of thymolipoma. In a review of the literature on the subject, some clinical features of this non-malignant tumor in the mediastinum are discussed. Although rare, thymolipoma should be considered in the differential diagnosis of mediastinal tumors. PMID- 2188031 TI - [Theoretical and technical bases of the performance of intestinal suture]. AB - A value of the effort necessary for approximation of the tissues of the sutured areas of the stomach and intestine has been defined, the physical phenomena occurring in tightening the sutures are described. PMID- 2188030 TI - Renal hemodynamics and segmental tubular reabsorption in early type 1 diabetes. AB - To investigate mechanisms underlying GFR control in diabetes mellitus, renal hemodynamics and segmental tubular handling of sodium, using lithium clearance, were assessed in 41 insulin-dependent diabetics (IDD) treated by insulin for 11 +/- 8 days, and in 19 normal controls. Average GFR and effective renal plasma flow (ERPF) were slightly but not significantly higher (136 +/- 22 vs. 123 +/- 16 ml/min.1.73 m2) in IDD than in normal subjects. GFR and ERPF were positively and strongly correlated in controls (r = 0.61, P less than 0.001) and in diabetics (r = 0.72, P less than 0.0001) indicating the marked flow dependency of GFR in both populations. After adjustment for ERPF, GFR was significantly higher in diabetics, suggesting a role of increased glomerular capillary pressure and ultrafiltration coefficient in the subset of "hyperfiltering" patients. Both fractional (FPRNa) and absolute (APRNa) proximal sodium reabsorption were significantly higher in IDD and significantly correlated with GFR. The ensuing decrease in sodium distal delivery could deactivate the tubuloglomerular feedback response and thus favor sustained vasodilation and high GFR in some diabetics. The renal effects of acute administration of drugs acting predominantly at either the pre- or the postglomerular resistance using nicardipine (N = 16) or captopril (N = 25) were further evaluated in IDD. The renal response to captopril or nicardipine was different in IDD. Whereas both drugs induced a marked decrease in renal vascular resistance, GFR was slightly decreased by captopril and was unchanged after nicardipine; these results are similar to those observed in normotensive non-diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188032 TI - [A new method of producing small-to-large intestine invagination anastomosis in experimental animals]. AB - A method for formation of the valve apparatus by means of invagination of the end of the small intestine with everted mucosa to the side of a large intestine directly to its stump is suggested. Beforehand the tela submucosa of the evaginated small intestinal end is exposed by linear incision, and is tightened into the interrupted sutures, which are placed on the large intestinal stump. When the pressure arises in the large intestinal lumen, the small intestinal end is pressed to the stump and flattened, thus preventing reflux. PMID- 2188033 TI - [Use of a manual intestinal suture in elimination of colostomy]. AB - The advantages of a suggested method for placing the intestinal suture in performance of the operations for liquidation of fistulas of the colon with restoration of its continuity are shown. PMID- 2188034 TI - [Acute hemorrhoids]. PMID- 2188035 TI - [A foreign body of the abdominal cavity which migrated to the intestinal lumen]. PMID- 2188036 TI - [Method of surgical treatment in postoperative and recurrent abdominal hernias]. PMID- 2188037 TI - [A device for placing continuous circular sutures]. PMID- 2188038 TI - [A method of surgical treatment of bleeding duodenal ulcer of large dimensions]. PMID- 2188039 TI - [Mononuclear phagocytes and their growth factors: pacemakers of proliferative vitreoretinopathy?]. AB - Recent studies on the natural course of proliferative vitreoretinopathy (PVR) have focused on the mononuclear phagocyte system (MPS). Although the precise origin of these cells is not known, current evidence indicates that peripheral blood monocytes infiltrate a lesion initially, subsequently giving way to resident phagocytic cells. In this context the authors try to clarify some aspects of the confusing nomenclature of phagocytic monocytes, macrophages, and microglia. The concept of the blood-retinal barrier (BRB) and its breakdown in PVR are presented and discussed. Platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta), both secretory products of macrophages, have recently been implicated in the development of vitreoretinal pathology. These studies, however, are difficult to evaluate because the biological effects of different growth factors are closely interrelated and vary widely, including both inhibition as well as stimulation of cell growth. The authors hypothesize that plasma of macrophage-derived TGF-beta provokes an increase in fibronectin synthesis, which in turn is responsible for the fibrotic rebuilding of the vitreoretinal interface in PVR. As an adjunct to the pharmacological treatment of PVR with Daunomycin the use of steroids is recommended to suppress the initial macrophage activation and related dysfunction of the BRB. PMID- 2188040 TI - [Biometry of the anterior chamber of the eye in Nd:YAG laser iridectomy]. AB - In a prospective clinical study covering 41 eyes (28 patients) with narrow-angle glaucoma the central and peripheral anterior chamber depths were determined biomicroscopically before and after Nd:YAG laser iridectomy. In 29 eyes the central anterior chamber depth was also measured by ultrasonography. In contrast to the increase in central anterior chamber depth, which was only slight, the increase in the peripheral anterior chamber depth was statistically significant (P less than 0.01). PMID- 2188041 TI - [The reliability of ultrasound biometry]. AB - Preoperative ultrasonic biometry is indispensible in cataract surgery in order to calculate the power of the intraocular lens to be implanted. Various authors have suggested that the accuracy of the measurements could be improved by performing biometry several times and basing the calculation of the lens on the mean value. The problem of the retest reliability of ultrasonic measurements was investigated in 99 young subjects with healthy eyes and 60 cataract patients. Biometry was performed three times consecutively in each mode using three different scanners and different coupling techniques. A comparison of the consecutive measurements showed good agreement (between r = 0.96 and r = 0.99) in regard to axial length and hence very good retest reliability. The accuracy of the repeat measurements was approximately the same with all three coupling methods used. The correlation coefficients of retest measurements of anterior chamber depth and lens thickness were much lower (r = 0.78 to r = 0.96). This may be explained by differences in handling of the probes, in the test modes, and in the physical conditions on which the measurements are based. In view of the good reproducibility of axial length measurements the authors consider one carefully performed biometry more valuable for preoperative calculation of lens power than the mean of several measurements. PMID- 2188042 TI - [Erich Zeiss (1894-1975)--the first inventor of non-contact tonometry]. AB - The first inventor of non-contact tonometry was the German ophthalmologist Erich Zeiss, grandson of Carl Zeiss. In 1951 he designed a "pneumatic" tonometer or "aerotonometer". A patent application was prepared but, regrettably, never sent to the Patent Office. This article pays tribute to Zeiss' achievements as a designer of ophthalmologic instruments. PMID- 2188043 TI - [Calcitonin and osteoporosis--a critical review of the literature 1980-1989]. AB - Due to increasing old age and a prolonged life expectancy osteoporoses mainly of the involutional type have become very common and are thus of prime socio-medical importance. Recently considerable attention has been given to calcitonin as an aetiologic, prophylactic and therapeutic agent in osteoporosis. Since the subject is very controversial, the present study aims at critically evaluating the pertinent literature from 1980-1989: 1. A decreased stimulability of the thyroid C-cells and thus a diminished calcitonin secretion capacity has been demonstrated in white postmenopausal women. However an overt calcitonin deficiency cannot be considered to be the only or a major cause of the osteoporotic bone loss. 2. An increased bone loss (occurring in phases?) may be stopped by calcitonin(s) given either parentally or by the intranasal route. This pharmacologic calcitonin effect does not differ from the well-known osteoclast inhibiting effect in Paget's disease and seems to be similar to estrogen bone effects in the menopause. 3. An increase of total body calcium (TbCa) of 1-4% and of the bone mineral content (BMC) has been reported occurring within 18-24 months of calcitonin administration in overt osteoporosis. However a reinforcement of the bone structure has not been shown, further crash fractures of vertebras occurring despite calcitonin administration for up to 2 years. Within this observation period the bone volume assessed histomorphometrically did not increase, unless calcitonin was combined with phosphates which were known to induce secondary hyperparathyroidism. 4. Repeatedly an analgesic efficacy has been ascribed to calcitonins, presumably due to a direct hormonal effect on calcitonin receptors in the brain. Since the pain in osteoporosis is extremely variable and often self limiting due to fracture healing the "calcitonin analgesia" has probably been over-estimated. PMID- 2188044 TI - [Terguride in hyperprolactinemia--experiences with 5 patients]. AB - Hyperprolactinemia can successfully be treated by dopaminagonists such as bromocriptin or lisuride. About 10% of patients complain about side effects like orthostatic hypotension, nausea or vomiting, which may lead to discontinuation of treatment. We therefore conducted a study using terguride--a new dopaminagonist- in 5 patients with hyperprolactinemia and intolerable side effects under conventional treatment. Terguride is the transdihydroderivative of lisuride (Dopergin). We treated 5 patients, 2 men with macroprolactinoma and 3 women with microprolactinoma with terguride. The mean duration of treatment was 15.6 months (7-37 months). Patients were treated with up to 5 mg terguride daily. All 5 patients had a marked initial decrease of elevated prolactin levels 8 h after administration of 0.25 mg terguride orally. Three patients became normoprolactinemic after sufficient increase of the dose of terguride, 2 female patients with a microprolactinoma got eumenorrhoeic thereafter. The treatment with terguride was tolerated without side effects by all patients. There were no significant changes of the examined parameters of clinical chemistry nor the other pituitary hormones. Results of cranial computertomography did not change in 4 patients, one patient had tumor progression. Tergurid as a dopaminagonist is an effective inhibitor of prolactin with little side effects and thus a useful drug in the treatment of hyperprolactinemia. PMID- 2188045 TI - Stromal-epithelial cell communication, growth factors, and tissue regulation. PMID- 2188046 TI - Extracellular deposition of eosinophil and neutrophil granule proteins in the IgE mediated cutaneous late phase reaction. AB - Intradermal injection of allergens in sensitive subjects produces an IgE dependent prolonged inflammatory reaction, the late phase reaction (LPR). Histologically, eosinophils are present in the LPR but are not as numerous as neutrophils or mononuclear cells. We determined whether extracellular deposition of eosinophil and neutrophil granule proteins occurs in the LPR by immunofluorescent localization of eosinophil granule major basic protein (MBP), eosinophil-derived neurotoxin (EDN), and neutrophil elastase. Before intradermal challenge, eosinophils and neutrophils were present only in blood vessels, and MBP, EDN, and elastase were localized to cells. At 15 minutes, small amounts of MBP, EDN and elastase were found outside of cells in focal areas. By 1 to 3 hours, MBP, EDN and elastase were extensively deposited throughout the dermis in a granular and diffuse manner; these deposits persisted up to 56 hours. Both actively and passively sensitized subjects showed similar MBP and elastase deposition. Skin sites passively sensitized by sera depleted of IgE showed essentially no MBP or elastase deposition. Electron microscopy showed degenerating eosinophils and free eosinophil granules in the dermis. Mast cell numbers diminished during the LPR when extracellular eosinophil and neutrophil granule protein deposition was maximal. These results demonstrate that striking dermal eosinophil and neutrophil granule protein deposits are prominent features of the cutaneous LPR, are IgE-dependent and precede the maximal clinical expression of the LPR. The possible significance of these findings in the pathophysiology of the LPR is discussed. PMID- 2188048 TI - On the construction of drinking norms in work organizations. AB - Alcohol abuse and dependence is the result of multiple risk factors. Although this article focuses primarily on workplace risk factors, it discusses them within a framework of biological, psychological, familial, social class and sociocultural risks, and argues that a comprehensive explanation of alcohol problems must encompass all of these factors. In addition, the article argues that by constructing drinking norms, especially within the context of the workplace, these risks may be contained and reduced. Consequently, the article also reviews data on the workplace strategy of constructive confrontation and calls for research on similar interventions for containing risks from outside the workplace. PMID- 2188047 TI - Environmental carcinogens--Percivall Pott revisited. PMID- 2188049 TI - [Anomalous partial pulmonary venous drainage]. PMID- 2188050 TI - The effect of hypertension and its treatment on cerebral cell volume regulation during hypernatremic dehydration. AB - Since hypertension may compromise the ability to withstand hypernatremic dehydration, we investigated the impact of two experimental models of hypertension and pharmacologic normalization of blood pressure on the tolerance to chronic hypernatremic dehydration. In DOCA-salt hypertensive animals and the spontaneously-hypertensive rat (SHR), there was increased mortality and cerebral cell shrinkage during hypernatremic dehydration, compared to control Sprague Dawley or Wistar-Kyoto rats. These findings were paralleled by significant differences in the brain intracellular water compartment size (ml/100 g dry weight), i.e. 233 +/- 6, Sprague-Dawley vs 189 +/- 8, DOCA-salt, P less than 0.01; 246 +/- 3, Wistar-Kyoto vs 194 +/- 6, SHR, P less than 0.01. Normalization of the blood pressure in the SHR with captopril restored 48% of the cerebral cell volume regulatory capacity observed in normotensive Wistar-Kyoto rats. We conclude that sustained hypertension increases the risk of hypernatremic dehydration in select circumstances. Correction of the elevated blood pressure promotes partial recovery of normal cerebral cell volume regulation. PMID- 2188051 TI - [Noninvasive radiodiagnosis of aneurysms of the thoracic aorta]. AB - The paper is concerned with analysis of the results of X-ray investigation of 45 patients with aneurysms of the distal part of the arch and descending part of the thoracic aorta. Errors were made in 16 of 35 patients (35.6%) before admittance to hospital. X-ray investigation helped to establish correct diagnosis of aneurysm of the aorta in 42 of 45 patients (93.3%) on the basis of the detection of intense additional shadow formation in left pulmonary field, inseparable from the aortic shadow. The use of a new method of ultrasound diagnosis--duplex scanning--made it possible to establish the presence of aneurysm and to determine its sizes as well as to visualize the relation of the left subclavicular artery to aneurysm in 17 of 21 patients. CT-semiotics of aneurysms of the descending part of the thoracic aorta consisted in its dilatation over 3.5 cm, wall calcification, thrombosis of the cavity and change of the adjacent structures. Basing on the analysis of these signs correct diagnosis was established in 34 of 35 examinees (97.1%). PMID- 2188052 TI - [Ultrasonic examination and lymphography in the diagnosis of metastases of rectal cancer]. AB - The diagnostic effectiveness of ultrasound and lymphographic investigations was assessed in 89 rectal cancer patients. Lymphography was shown to be a more informative method as it permitted the detection of metastases in 6 patients in whom USI results were negative, metastatic involvement in 2 patients, specifying the type of pathological changes of the enlarged lymph nodes in 14 patients. In a normal lymphographic picture metastatic involvement was detected in 37 cases using echography. More extended metastatic spreading was found on USI (as compared to lymphography) in one patient. The combined use of echography and lymphography improved the diagnosis of rectal cancer lymphogenous metastases. PMID- 2188053 TI - [The teaching of roentgenology and radiology in medical schools of higher education (historical outline)]. PMID- 2188054 TI - [Roentgenology and radiology in Soviet art]. PMID- 2188055 TI - [The significance of tumor size in radiotherapy using modifiers]. PMID- 2188056 TI - [Diagnostic research in endocrinology]. PMID- 2188057 TI - [Alumni of the I. M. Sechenov 1st Moscow Medical Institute in space]. PMID- 2188058 TI - [They fought to the death]. PMID- 2188059 TI - [The nurse on postage stamps of the Republic of Cuba]. PMID- 2188060 TI - Interleukin-6: a regulator of plasma protein gene expression in hepatic and non hepatic tissues. AB - The cytokine which is now called interleukin-6 (IL-6) has emerged as a major systemic alarm signal produced by essentially every injured tissue in response to almost every kind of damage. The hallmark of IL-6 gene regulation is its induction in many different tissues by inflammation-associated cytokines, bacterial products, virus infection and by activation of any of the three major signal transduction pathways (diacylglycerol, cAMP and Ca2(+)-activated). Many of these inducers act largely through a 23 base-pair "multi-response element" in the IL-6 promoter. Different tissues secrete multiple post-translationally modified forms of IL-6 (six protein species in the size range 23 to 30 kDa, and additional forms of size greater than or equal to 45 kDa). IL-6 plays a key role in activating a variety of host defence mechanisms that are aimed at limiting tissue injury. Thus, IL-6 elicits major changes in the biochemical, physiological and immunological status of the host (e.g. the "acute phase" plasma protein response). IL-6 enhances plasma protein gene expression not only in hepatocytes but also in monocytes, fibroblasts and lymphocytes. Elevated levels of IL-6 are observed in body fluids during acute and chronic infections, neoplasia and autoimmune diseases. The nature of the IL-6 receptor in hepatic and non-hepatic cells, the different signal transduction pathways involved in the regulation of particular liver genes by IL-6, the association between IL-6 levels in body fluids and clinical outcome and between IL-6 haplotypes and specific disease states remain to be explored in detail. PMID- 2188061 TI - Genetics of alpha 1-antitrypsin deficiency in relation to neonatal liver disease. AB - Homozygosity for alpha 1-antitrypsin deficiency, usually of the genotype PIZZ, is one of the more common single gene defects in infants of European origin, occurring in about 1 in 2000 to 1 in 7000 of the newborn population. About 17% of such infants present with neonatal hepatitis and a small number with intracranial haemorrhage thought to be caused by vitamin K deficiency associated with cholestasis. At least 3% of PIZZ infants will die of cirrhosis in later childhood unless successfully treated by liver transplant. The pathogenesis of the liver disease is not understood and this is unsatisfactory both for treatment and for genetic counselling. The locus coding for alpha 1-antitrypsin (alpha 1AT) is designated PI for proteinase inhibitor. Careful study of the genotypes at this locus in neonatal disease shows that the only certain association is with the homozygous PIZZ genotype. The mutation results in a normal rate of synthesis of a polypeptide that becomes entrapped in the endoplasmic reticulum of the hepatocyte. Some other factor (or factors), as yet unidentified, determines whether severe liver damage results. The low level of alpha 1AT in the plasma seems unlikely to be the primary cause of damage but may play a secondary role. There is some evidence that the other factor(s) may be familial since in one study, though not in all, a high correlation for severity of liver disease was found between PIZZ siblings. The heterogeneity of the clinical course does not result from heterogeneity of PIZ alleles and there is no evidence that it is determined by variation in other related genes on chromosome 14. Only two possible clues have emerged so far. There is some evidence of a protective effect of breast-feeding, and a recent study has found the HLA class II DR3 antigen to be more common than expected in children with alpha 1-antitrypsin deficiency and liver disease. Accumulation of alpha 1AT protein in the hepatocytes may predispose them to some unidentified alteration of the immune response. It is possible that lack of antiprotease activity in the plasma might exacerbate the original damage, so the possibility of useful therapy with alpha 1AT cannot be ruled out entirely. At present, there is no valid way of predicting the severity of disease in a PIZZ child; hence, it is common for parents of a severely affected child to wish to terminate any future PIZZ pregnancy. The most direct method to diagnose the PIZZ genotype of a chorion villus sample is by allele specific hybridization or sequencing of amplified DNA.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2188062 TI - Anatomy of the rat albumin promoter. AB - The sequences preceding the albumin mRNA start site are able to direct efficient transcription only upon introduction into cells expressing the endogenous albumin gene. In transient expression assays, the activity of a reporter gene (CAT) linked to this promoter is 100-fold higher in H4II differentiated hepatoma cells than in H5 dedifferentiated cells which no longer express their albumin gene. This tissue specificity depends on the very proximal promoter region, composed of a CCAAT box, the proximal element and a TATA box. Deletion of the CCAAT box leads to a two- to threefold decrease in activity, deletion of the proximal element (PE) results in loss of activity. The PE is a high-affinity binding site for HNF1/APF, a strictly liver specific trans-acting factor. When the affinity of this factor for PE is decreased by bacterial methylation (PE includes a dam methylase site), by mutation, or by its replacement with the homologous element from the alpha-fetoprotein gene (AFP), the activity of the short promoter (PE plus the TATA box) is abolished. This activity can be rescued in the presence of the more upstream elements: DEII, DEI and the CCAAT box (recognized, respectively, by the NF1/CTF, C/EBP and NFY/ACF factors) which are then absolutely required. Our results suggest that the upstream elements contribute to promoter activity by stabilizing the HNF1-PE complex and not by direct interaction with TFIID or the RNA polymerase. It is probable that these elements, essentially dispensable in already differentiated hepatoma cells, play a crucial role during development or differentiation to activate the promoter in cells that contain a low concentration of HNF1 and/or an HNF1 unable to open inactive chromatin alone. PMID- 2188063 TI - Chemically induced aneuploidy in higher plants. AB - Although there is extensive literature reporting aneuploidy in plants there has been little consideration of the mechanisms of induction of the observed changes in chromosome number and the role of environmental agents in its induction. This paper collates and analyses the literature on aneuploidy induction in plants with the aim of identifying the mechanisms involved. Many of the major events that occur during cellular segregation, such as respiration, spindle and phragmoplast functions and chromosome doubling, appear to be stressed by agricultural chemicals, drugs, natural and industrial products, leading to aneuploidy in both the mitotic and meiotic cells of approximately 60 plant species. Of the nearly 400 chemicals at present suspected to be aneugenic to plants, approximately 150 are agricultural chemicals, 60 are drugs, 60 are natural substances and 50-60 are industrial products. Nearly half of these agents were reported to affect spindle mechanisms in mitosis and meiosis. About 60 affected phragmoplast function in root meristems. Another 60 chemicals appear to modify chiasma frequencies. Nearly 40 chemicals appear to be clastogenic in such a way that could lead to aneuploidy by a secondary mechanism. About 45 plant species exhibit aneuploidy without any apparent cause or source of stress. This could arise from several metabolic and anthropogenic causes operating alone or together such as: (i) the nutritional status of the soil, (ii) irrigation by polluted water, (iii) the ageing of seeds, (iv) pathogenesis of plants, (v) cryptotoxins in plants, (vi) pesticide applications and (vii) pesticide residues. Environmental factors such as pH and temperature may further compound these stresses. Among the biota, plant systems alone seem to possess all the components to monitor every conceivable type of aneuploidy and respond to all kinds of stress in our environment. There are deficiencies in the work hitherto carried out which need to be rectified. Some aspects have to be reinvestigated with improved protocols. For a perspective understanding of the phenomenon of aneuploidy, so vital to human systems, it is imperative that we devise new approaches, some of which are outlined here. PMID- 2188064 TI - The influence of excision repair on the distribution of N-propyl-N'-nitro-N nitrosoguanidine-induced mutation in Escherichia coli. AB - To determine the influence of excision repair on the distribution of N-propyl-N' nitro-N-nitrosoguanidine (PNNG)-induced mutation, we have analysed the DNA sequence changes of mutation induced at the lacI gene of Escherichia coli in a UvrB- strain. The mutagenic specificity was similar to that found in the wild type strain. Base substitutions predominate; G:C----A:T transitions accounted for almost 75% of the mutational events, while G:C----T:A transversions constituted approximately 20% of the mutations. In both strains the distribution of G:C--- A:T transitions was nonrandom, but the site specificity of the G:C----A:T transitions appear dissimilar, with the hot and cold sites occurring at different positions. A single - 1 frameshift was recovered in each strain but deletion events were absent in the excision-repair-deficient strain. The complexity of the sequence-specificity of PNNG might reflect the differential repair of n-propyl and iso-propyl adducts. PMID- 2188065 TI - Structural basis of the mutagenicity of 1-amino-2-naphthol-based azo dyes. AB - A structure-activity study of 1-amino-2-naphthol derived azo dyes using CASE, the Computer Automated Structure Evaluation system, revealed that for optimal mutagenicity, reduction of the azo bond was required, thus suggesting that activity could be related to the liberated aromatic amines. Although it has long been known that sulfonation of azo dyes resulted in decreased carcinogenicity and mutagenicity, the present study elucidates the sites of sulfonation which will decrease mutagenicity maximally. Comparison of CASE predictions with available mutagenicity data indicates a concordance. Unexpectedly, CASE indicates that one of the aromatic amines obtained upon azo reduction of FD and C Red no. 40 is predicted to be mutagenic. PMID- 2188066 TI - In vivo genotoxic effects in mice of Metacid 50, an organophosphorus insecticide. AB - The genotoxic effect of methyl parathion, an organophosphorus insecticide commercially available as Metacid 50, was studied in Swiss albino mice using bone marrow and peripheral blood micronucleus tests. Single acute oral doses of the insecticide at concentrations of 75.0, 37.5, 18.75 and 9.375 mg/kg body weight, equivalent to 1/2 LD50, 1/4 LD50, 1/8 LD50 and 1/16 LD50, administered to female mice, elicited positive responses in bone marrow and peripheral blood micronuclei tests. Statistically significant increases in the frequency of micronuclei were observed at higher doses in both the tests performed. The data obtained for our experiments suggest that methyl parathion is a potent mutagen and so it is also likely to have a genotoxic effect in humans. PMID- 2188068 TI - The use of historical data for identifying biologically unimportant but statistically significant results in genotoxicity assays. AB - The definition of a negative result is a problem in genetic toxicology. Here we suggest that a result may be considered biologically unimportant (negative) if it falls within the limits of variation usually found in the negative controls of the particular test. To determine 'usual' variation, we have set 95% confidence limits on three indices of variation, calculated from historical values for duplicate negative control data from several genotoxicity tests. These tests showed four characteristic types of response and the appropriate index of variability was determined for each. Where there was little test-to-test variation in true mean (micronucleus test and metaphase analysis), confidence limits set on the overall distribution of negative controls were the best index of variability. In other assays (Ames, yeast and mouse lymphoma), there was considerable test-to-test variation so that differences between, or ratios of, the members of control duplicates were the preferred measure of variability. This approach can define what is biologically unimportant in terms of the test system. However, no inference can be drawn as to potential importance. Thus the main use is the removal of the positive 'label' from statistically significant results which fall within the usual range of spontaneous variation for the assay under consideration. PMID- 2188067 TI - Mutagenicity of oxidized microsomal metabolites of 1-nitropyrene in Chinese hamster ovary cells. AB - 1-Nitropyrene, a tumorigenic environmental pollutant, is mutagenic in Chinese hamster ovary (CHO) cells in the presence of a liver homogenate 9000 g supernatant fraction (S9). The metabolic pathways involved in this response were studied by comparing the mutagenicities at the hypoxanthine-guanine phosphoribosyl transferase locus of 1-nitropyrene, some oxidized microsomal metabolites of 1-nitropyrene, and related compounds. In the absence of S9, pyrene 4,5-oxide and 6-hydroxy-1-nitropyrene displayed the highest mutagenicities, followed by 1-nitropyrene 9,10-oxide and 1-nitropyrene 4,5-oxide; 3- and 8 hydroxy-1-nitropyrene were weaker mutagens, while pyrene and 1-nitropyrene were essentially without activity. With S9, the order of mutagenic potency was 1 nitropyrene 4,5-oxide greater than 6-hydroxy-1-nitropyrene approximately 1 nitropyrene 9,10-oxide greater than 1-nitropyrene approximately 3-hydroxy-1 nitropyrene approximately 8-hydroxy-1-nitropyrene greater than pyrene approximately pyrene 4,5-oxide, with the latter two compounds being essentially inactive. Inclusion of the epoxide hydrolase inhibitor 1,2-epoxy-3,3,3 trichloropropane during the S9-mediated treatment of CHO cells with 1-nitropyrene increased mutation induction 5-fold. Also, liver microsomes prepared from guinea pigs treated with Aroclor 1254 mediated a stronger mutagenic response with 1 nitropyrene than microsomes from Aroclor-treated rats. 1-Nitropyrene was essentially non-mutagenic in the presence of microsomes from untreated and phenobarbital-treated rats. Examination of the 1-nitropyrene metabolites produced during the microsomal incubations indicated that Aroclor-induced guinea-pig microsomes yielded substantial amounts of 1-nitropyrene 4,5-dihydrodiol, while Aroclor-induced rat microsomes produced 6-fold more 6- and 8-hydroxy-1 nitropyrene than phenobarbital microsomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188070 TI - O6-methylguanine-DNA methyltransferase activities from exponentially growing human T lymphocytes: similar activities in controls and Alzheimer's disease patients. AB - O6-Methylguanine-DNA methyltransferase (MT) specific activity (fmol/mg protein) was measured in human T lymphocytes which were maintained as exponentially growing cultures from 6 to 17 days. The T lymphocytes were not transformed and were grown under the same conditions used previously for determination of spontaneous human mutant frequencies. Although large inter-individual differences in activity were found, the differences were not attributable to donor age, sex or time in culture. The reported specific activity results, including the age and sex independence, were similar to other laboratories even though non-cultured peripheral blood T lymphocytes were previously used. Since cells from Alzheimer's disease (AD) patients have been shown to be overly sensitive to alkylation damage induced by N-methyl-N'-nitro-N-nitrosoguanine, and since no one has previously assayed MT activity in cells from AD patients, we compared MT activities in cultured T lymphocytes from AD patients, healthy controls and neurological controls. Similar levels of MT specific activity were found in each category analysed. PMID- 2188069 TI - Chloroacetaldehyde is a powerful inducer of mitotic aneuploidy in Aspergillus nidulans. AB - The vinyl chloride metabolite chloroacetaldehyde (CAA) was tested for the induction of mitotic chromosome malsegregation in Aspergillus nidulans. Exposure of germinating conidia to CAA (16-64 microM) produced high rates of abnormal colonies with segregation of the whole first chromosome in the diploid strain P1, and abnormal, putative hyperploids in the haploid strain 35, indicating that CAA primarily induces abnormal chromosome segregation. Comparative assays with the known spindle poison chloral hydrate (CH), active in the dose range 6-10 mM, highlighted the unusual effectiveness of CAA in aneuploidy induction (the lowest effective concentration was 16 microM). Experiments on brain tubulin polymerization revealed an inhibitory effect by CAA only at concentrations 100 fold higher than those active in the induction of chromosome misdistribution in A. nidulans, possibly suggesting the involvement of alternative targets in its mechanism of action. PMID- 2188071 TI - Induction of frameshift mutations by caffeine in Escherichia coli K12. AB - Caffeine induced reversions of five different frameshift mutations in Escherichia coli K12. Only those mutations which were very sensitive to reversion-induction by 9-amino-acridine (9AA) were also sensitive to caffeine. Caffeine mutagenesis was not due to inhibition of cellular repair functions, but to the production of replication errors, which were corrected very efficiently by mismatch repair. From the results reported here we conclude that the targets for caffeine mutagenesis are long runs of GC base pairs, and that this mutagen induces -1 frameshifts. PMID- 2188072 TI - Concurrent detection of gene mutations and chromosomal aberrations induced in vivo in somatic cells. AB - A simple direct assay for gene mutations in vivo is the missing assay in genetic toxicology. Here we report that both gene mutations and chromosomal aberrations induced in vivo can be reliably detected and quantified in a single cell type. Lung cells were isolated and cultured from Chinese hamsters that had been exposed to model mutagenic carcinogens, and then analysed in culture for genetic alterations. Chromosomal aberrations were assayed by the frequency of micronuclei found in binucleate cells after growth in the presence of cytochalasin B. Mutations were assayed by the frequency of thioguanine-resistant colonies on the 10th day of culture. X-rays and ethyl nitrosourea produced detectable increases in both mutations and chromosomal aberrations. Ethyl methanesulphonate produced large numbers of mutations but no chromosomal aberrations and methyl methanesulphonate produced the inverse: large numbers of chromosomal aberrations but no mutations. Our experience with these agents and the procedure suggests a standard protocol for the assay, and confirms the value of measuring both gene mutations and chromosomal aberrations. PMID- 2188073 TI - Genetic effects of 2-aminopurine in mammalian cells. AB - The effects of 2-aminopurine (APur) on mutations, sister-chromatid exchanges (SCEs) and proliferation were investigated in V79 cells by means of cytogenetic and flowcytometric experiments. APur did not induce SCEs after a 3-h treatment before the addition of BrdUrd but SCE frequencies were increased after treatment for two cell cycles in the presence of BrdUrd. SCEs were mainly produced during the second cell cycle of the SCE experiment when BrdUrd substituted DNA is replicated. APur also caused a high percentage of polyploid cells. Compared on the basis of DNA content, SCE induction was the same in diploid and tetraploid metaphases. APur-induced SCEs are strongly influenced by nucleosides. The presence of deoxycytidine (dCyd) caused a reduction of AP-induced SCEs to about control level while addition of deoxythymidine (dThd) enhanced SCE induction. Flow cytometric measurements revealed a small increase in S-Phase cells and a strong accumulation in G2/M after APur treatment in the presence of BrdUrd. S phase delay was strongly enhanced when BrdUrd substituted DNA is replicated. Addition of dCyd removed the APur-induced inhibition of S-phase in both protocols. Using the same treatment protocol, APur also induced mutations at the HPRT locus. In contrast to their effects on SCEs and proliferation neither BrdUrd nor dCyd had an effect on APur-induced mutations, and dThd reduced the mutation frequency. The results demonstrate that APur-induced SCEs and mutations occur independently from each other. APur-induced mutations obviously occur by a mispairing mechanism while SCEs are a consequence of pool imbalances during replication. PMID- 2188074 TI - Molecular aspects of chemical mutagenesis in L5178Y/tk +/- mouse lymphoma cells. AB - Southern blot analyses were performed on DNA from at least 10 large and 10 small colony thymidine kinase-deficient (tk -/-) mutants induced by each of 10 mutagens [2-amino-N6-hydroxyadenine (AHA), ethyl methanesulfonate (EMS), methyl methanesulfonate, 2-acetylaminofluorene, methotrexate, caffeine, methapyrilene, 4 (9-acridinylamino)-methanesulfo-m-anisidide, hycanthone methanesulfonate and procarbazine]. Two molecular mutant genotypes were recognized upon digestion with NcoI and subsequent probing with a 1.1 kb cDNA insert from plasmid pMtk 4: (i) no detectable alteration, and (ii) the absence of the functional tkb allele as indicated by the absence of the 6.3 kb fragment. In combination with the previously established chromosomal nature of most small colony tk -/- mutants, this permitted the classification of these 10 mutagens according to the relative proportions of each of four classes of genetic damage they induced. AHA and EMS gave mutational spectra consistent with their point mutational effects in other systems. The other eight mutagens induced mostly small colony mutants, most of which had lost the entire original tkb allele. Methotrexate induced high frequencies of large colony mutants at the tk locus, most of which lacked the tkb allele, although it is weakly or non-mutagenic at the hemizygous hprt locus in these same cells. At least three of these mutagens-methotrexate, caffeine, methapyrilene (and possibly procarbazine)--lack structural alerts for DNA reactivity, implying a major class of non-DNA primary targets for mutagenicity in mammalian cells that interact secondarily with the chromosome. These results are discussed in relation to the known differences in sensitivity among various short term tests for genotoxicity. PMID- 2188075 TI - 'Cryptic' mutagens and carcinogenicity. AB - CASE, the Computer Automated Structure Evaluation method, predicts that a fraction of the chemicals identified as 'non-genotoxic' carcinogens, i.e. rodent carcinogens which are not mutagenic in Salmonella, are, in fact, potential Salmonella mutagens. These chemicals are termed 'cryptic mutagens', i.e. agents that possess structural determinants which endow them with potential mutagenicity. Even though this potential is not expressed in Salmonella, it may be expressed in other systems such as in the mutagenic activation of oncogenes. PMID- 2188076 TI - An improved method for the 'in vitro' micronucleus test using human lymphocytes. PMID- 2188077 TI - DYNASCENE: an approach to computer-based intelligent cardiovascular monitoring using sequential clinical "scenes". AB - Hemodynamic abnormalities such as hypovolemia typically progress through a sequence of discrete clinical phases or "scenes" (e.g., intravascular volume depletion, vasoconstriction, hypotension). Each scene can be defined by a cluster of hemodynamic trends. A natural approach to modeling the process of hemodynamic monitoring involves identifying these scenes and the temporal relationships among them. This approach has been utilized in the development of DYNASCENE, a parallel programming implementation of a computer-based intelligent hemodynamic monitor. This paper discusses: (1) The rationale for utilizing sequential clinical scenes to represent knowledge of hemodynamic behavior, (2) the design of the DYNASCENE system, and (3) preliminary tests of the DYNASCENE system. PMID- 2188078 TI - Development of a computer-aided reference system for differential diagnostics support. AB - In a situation of uncertain diagnosis, physicians may spend valuable time consulting relevant literature, often with unsatisfactory results. Therefore, our aim was to develop a computer system which supports differential diagnostics via rapid and comprehensive searches through information in literature. Based on entered signs and symptoms our prototype is able to offer probable diagnoses. Subsequently, further examinations and tests are suggested to confirm or exclude a certain disease. Thus, the final diagnosis is made gradually by differentiation of possible diseases. Our first attempt consisted in representing knowledge in a rule-based PROLOG system. However, because nearly all information for a sign oriented differential diagnosis can be represented with very few relations only, we turned to a fact-oriented representation of signs and diseases. Access was possible via PROLOG or an imperative programming language. The index-sequential access on a fact-oriented representation of knowledge was suitable to manage a large knowledge base, which is necessary for a thorough differential diagnosis. A pointer structure was recently examined in order to handle different object-to object relations. Efficient information processing is now possible which provides short response times using even broad knowledge bases. PMID- 2188079 TI - Expert systems for the prediction of ovulation: comparison of an expert system shell (Expertech Xi Plus) with a program written in a traditional language (BASIC). AB - The use of an expert system shell (EXPERTECH Xi Plus) in the construction of an expert system for the diagnosis of infertility has been evaluated. A module was devised for predicting ovulation from the medical history alone. Two versions of this system were constructed, one using the expert system shell, and the other using QuickBASIC. The two systems have been compared with respect to: (1) ease of construction; (2) ease of knowledge base update; (3) help and explanation facilities; (4) diagnostic accuracy; (5) acceptability to patients and clinicians; (6) user-friendliness and ease of use; (7) use of memory space; and (8) run time. The responses of patients and clinicians were evaluated by questionnaires. The predictions made by the computer systems were compared to the conclusions reached by clinicians and to the "gold standard" of day 21 progesterone. The conclusions of this pilot study are: (1) the construction of this expert system was NOT facilitated by the use of this expert system shell; (2) update of the knowledge base was not facilitated either; (3) the expert system shell offered built-in help and explanation facilities, but as the system increased in complexity these became less useful; (4) after initial adjustment of decision thresholds the diagnostic accuracy of the system equalled that of the clinician; (5) the patient response to computer history-taking was very favorable but much less favorable to computer diagnosis; (6) the clinicians took a positive attitude to computer diagnosis; (7) the systems were easy to use; (8) the expert systems shell required much more memory space and had a much slower response time than the system written in BASIC. PMID- 2188080 TI - Inter-observer variation in decision-making regarding patients on chronic hemodialysis: a study using the kappa index. AB - To examine inter-observer variation in the monitoring of patients with chronic disease, four nephrologists independently assessed 62 patients on maintenance hemodialysis. Deviation from normal was determined for adequacy of dialysis, protein intake, and metabolic state. The kappa-index, which allows to adjust for chance agreement, was used to analyze each monitoring diagnosis. Low agreement was found on decisions concerning adequacy of dialysis (kappa 0.12-0.26), while agreement was higher about protein intake (kappa 0.21-0.46), and metabolic state (kappa 0.24-0.52). Two physicians classified no patient as overdialyzed, while 16 18% were thus categorized by the other two. Routines for review of recent medical history also differed significantly between the physicians. Measures are needed to increase the reliability of decisions regarding the monitoring of chronic hemodialysis. A long lasting physician-patient relationship is not a sufficient prerequisite for diminishing decision variation. Medical audit as part of the clinical routine, and use of additional sources of information, exemplified by urea kinetic modeling, are discussed. PMID- 2188081 TI - Use of information from clinical trials for an integrated cancer registry. AB - The registry of childhood malignancies in the F.R.G. is a combination of a population-based and hospital-based cancer registry. A large amount of the collected data originates from multicenter clinical trials which are integrated into the documentation system of the cancer registry. The paper describes the information flow and the system of data storage which consists of a central database on a departmental system at the registry and of several coordinated peripheral databases on microcomputers at the trial centers. Practical experience shows an increased availability and validity of the data in the registry since the implementation of the system. Aspects of data integrity and security are discussed. Although the system was designed according to specific demands of the registry, it may serve as a model for similar tasks of cooperative documentation and information exchange. PMID- 2188082 TI - [Leiomyomatosis of the gastrointestinal and urogenital tract in combination with hereditary nephritis]. PMID- 2188083 TI - [The relationship between lichen ruber planus orale, hepatopathies and hypersensitivity to the components of dental restorations]. AB - A group of patients with lichen planus, a pathology affecting the cutis and mucosa which may affect the oral cavity, were studied. All patients underwent laboratory tests to assess hepatic function. Prick tests, using a series of haptens found in materials used in dental reconstruction work, were also performed in 53 patients who possessed dental prostheses. The statistically significant correlation between lichen planus, especially in its erosive form, and hepatic damage is underlined. However, the correlation between sensitivity to the haptens contained in materials for dental reconstruction work and lichen planus was not significant. PMID- 2188084 TI - [Samples of iliac crest bone. A case report review and clinico-statistical evaluation]. AB - The paper examines 91 cases of iliac crest bone samples used in maxillofacial surgery for different purposes and evaluates the immediate and later complications which arise in the site of origin. The most frequent immediate complications are walking difficulties, hematoma, and sensitivity disturbances. Later complications usually include: esthetic deficits (depression of the crestal surface), walking difficulties, and a persistent neurological deficit. The complications observed substantially match those reported in the literature. PMID- 2188085 TI - [Instruments and technics for removing the restorations in fixed prostheses. a bibliographic analysis]. PMID- 2188086 TI - [Ameloblastic fibro-odontoma. A case report]. PMID- 2188087 TI - Isolation of the gene encoding the Saccharomyces cerevisiae centromere-binding protein CP1. AB - CP1 is a sequence-specific DNA-binding protein of the yeast Saccharomyces cerevisiae which recognizes the highly conserved DNA element I (CDEI) of yeast centromeres. We cloned and sequenced the gene encoding CP1. The gene codes for a protein of molecular weight 39,400. When expressed in Escherichia coli, the CP1 gene directed the synthesis of a CDEI-binding protein having the same gel mobility as purified yeast CP1. We have given the CP1 gene the genetic designation CEP1 (centromere protein 1). CEP1 was mapped and found to reside on chromosome X, 2.0 centimorgans from SUP4. Strains were constructed in which most of CEP1 was deleted. Such strains lacked detectable CP1 activity and were viable; however, CEP1 gene disruption resulted in a 35% increase in cell doubling time and a ninefold increase in the rate of mitotic chromosome loss. An unexpected consequence of CP1 gene disruption was methionine auxotrophy genetically linked to cep1. This result and the recent finding that CDEI sites in the MET25 promoter are required to activate transcription (D. Thomas, H. Cherest, and Y. Surdin Kerjan, J. Mol. Biol. 9:3292-3298, 1989) suggest that CP1 is both a kinetochore protein and a transcription factor. PMID- 2188088 TI - Glucagon and p21 ras enhance the phosphorylation of the same 38-kilodalton membrane protein from rat liver cells. AB - We had reported earlier the enhanced phosphorylation of a 38-kilodalton protein (p38) in rat liver plasma membrane by ras proteins. Now we show that glucagon increased the phosphorylation of the same protein. The nature and site(s) of phosphorylation were the same as those for the ras proteins. Both ATP and GTP could donate phosphate for the phosphorylation of p38. The stimulation of p38 phosphorylation by glucagon was guanine nucleotide dependent. This observation, together with our data on the stimulation of p38 phosphorylation by AIF4-, suggest the involvement of G proteins in the reaction. We also showed that glucagon stimulates the phosphorylation of p38 in vivo. PMID- 2188089 TI - Expression of the K-fgf proto-oncogene is controlled by 3' regulatory elements which are specific for embryonal carcinoma cells. AB - Expression of the K-fgf/hst proto-oncogene appears to be restricted to cells in the early stages of development, such as embryonal carcinoma (EC) cells. When EC cells are induced to differentiate, K-fgf expression is drastically repressed. To identify cis-acting DNA elements responsible for this type of regulation, we constructed a plasmid in which cat gene expression was driven by about 1 kilobase of upstream K-fgf human DNA sequences, including the putative promoter, and transfected it into undifferentiated F9 EC cells or HeLa cells as prototypes of cells which express or do not express, respectively, the K-fgf proto-oncogene. This plasmid was essentially inactive in both cell types, and the addition of more than 8 kilobases of DNA sequences upstream of the K-fgf promoter did not lead to any increase in chloramphenicol acetyltransferase (CAT) expression. On the other hand, when we inserted in this plasmid DNA sequences which are 3' of the human K-fgf coding sequences, we could detect a significant stimulation of CAT activity. Analysis of these sequences led to the identification of enhancerlike DNA elements which are part of the 3' noncoding region of K-fgf exon 3 and promote CAT expression only in undifferentiated mouse F9 or human NT2/D1 EC cells, but not in HeLa, 3T3, or differentiated F9 cells, therefore mimicking the physiological expression of the K-fgf proto-oncogene. Similar elements are also present in the 3' region of the murine K-fgf proto-oncogene, in a region showing high homology to the human K-fgf sequences. These regulatory elements can promote CAT expression from heterologous promoters in an EC-specific manner, suggesting that they interact with a specific cellular transacting protein(s) whose expression is developmentally regulated. PMID- 2188090 TI - RAD10, an excision repair gene of Saccharomyces cerevisiae, is involved in the RAD1 pathway of mitotic recombination. AB - The RAD10 gene of Saccharomyces cerevisiae is required for the incision step of excision repair of UV-damaged DNA. We show that the RAD10 gene is also required for mitotic recombination. The rad10 delta mutation lowered the rate of intrachromosomal recombination of a his3 duplication in which one his3 allele has a deletion at the 3' end and the other his3 allele has a deletion at the 5' end (his3 delta 3' his3 delta 5'). The rate of formation of HIS3+ recombinants in the rad10 delta mutant was not affected by the rad1 delta mutation but decreased synergistically in the presence of the rad10 delta mutation in combination with the rad52 delta mutation. These observations indicate that the RAD1 and RAD10 genes function together in a mitotic recombination pathway that is distinct from the RAD52 recombination pathway. The rad10 delta mutation also lowered the efficiency of integration of linear DNA molecules and circular plasmids into homologous genomic sequences. We suggest that the RAD1 and RAD10 gene products act in recombination after the formation of the recombinogenic substrate. The rad1 delta and rad10 delta mutations did not affect meiotic intrachromosomal recombination of the his3 delta 3' his3 delta 5' duplication or mitotic and meiotic recombination of ade2 heteroalleles located on homologous chromosomes. PMID- 2188091 TI - Mutational activation of c-raf-1 and definition of the minimal transforming sequence. AB - A series of wild-type and mutant raf genes was transfected into NIH 3T3 cells and analyzed for transforming activity. Full-length wild-type c-raf did not show transforming activity. Two types of mutations resulted in oncogenic activity similar to that of v-raf: truncation of the amino-terminal half of the protein and fusion of the full-length molecule to gag sequences. A lower level of activation was observed for a mutant with a tetrapeptide insertion mapping to conserved region 2 (CR2), a serine- and threonine-rich domain located 100 residues amino-terminal of the kinase domain. To determine essential structural features of the transforming region of raf, we analyzed point and deletion mutants of v-raf. Substitutions of Lys-56 modulated the transforming activity, whereas mutation of Lys-53, a putative ATP binding residue, abolished it. Deletion analysis established that the minimal transforming sequence coincided precisely with CR3, the conserved Raf kinase domain. Thus, oncogenic activation of the Raf kinase can be achieved by removal of CR1 and CR2 or by steric distortion and requires retention of an active kinase domain. These findings are consistent with a protein structure model for the nonstimulated enzyme in which the active site is buried within the protein. PMID- 2188092 TI - Myeloid expression of the human c-fps/fes proto-oncogene in transgenic mice. AB - The mammalian c-fps/fes proto-oncogene encodes a 92-kilodalton cytoplasmic protein-tyrosine kinase (p92c-fes), which is expressed in immature and differentiated hematopoietic cells of the myeloid lineage. To determine the limits of the c-fps/fes locus and to investigate the cis-acting sequences required to direct appropriate tissue-specific expression, a 13-kilobase-pair fragment of human genomic DNA containing the entire c-fps/fes coding sequence was introduced into the mouse germ line. Transcription of the human c-fps/fes transgene was highest in bone marrow and showed a tissue distribution identical to that of the endogenous mouse gene. Macrophages cultured from transgenic mouse bone marrow contained particularly high levels of human and murine c-fps/fes RNA. Furthermore, expression of human c-fps/fes RNA induced a proportionate increase in the level of the p92c-fes protein-tyrosine kinase in bone marrow, bone marrow derived macrophages, and spleen. Elevated levels of normal human p92c-fes had no obvious effect on mouse development or hematopoiesis. Remarkably, given the short 5'- and 3'-flanking sequences, expression of the human proto-oncogene in bone marrow was independent of integration site, was proportional to the transgene copy number, and was of comparable efficiency to that of the endogenous mouse c fps/fes gene. The 13-kilobase-pair fragment therefore defines a genetic locus sufficient for the appropriate tissue-specific expression of the fps/fes protein tyrosine kinase and includes a dominant cis-acting element that directs integration-independent myeloid expression in transgenic mice. PMID- 2188093 TI - SNF6 encodes a nuclear protein that is required for expression of many genes in Saccharomyces cerevisiae. AB - The SNF6 gene appears to affect transcription from a variety of promoters in Saccharomyces cerevisiae. The gene was cloned, and sequence analysis revealed two completely overlapping open reading frames of 996 and 1092 nucleotides on opposite strands. The SNF6 coding sequence was identified by selective mutagenesis. The predicted 37,604-dalton SNF6 protein is highly charged but overall neutral. A bifunctional SNF6-beta-galactosidase fusion protein was localized in the nucleus, as judged by immunofluorescence microscopy. The N terminus of SNF6 contains a sequence homologous to nuclear localization signals and was sufficient to direct beta-galactosidase to the nucleus. The 5' ends of the SNF6 RNA were heterogeneous and included ends mapping downstream from the first ATG codon. Construction of a frameshift mutation provided evidence that translational initiation at the second ATG yields a partially functional SNF6 product. Null mutations in SNF6 caused a wider range of pleiotropic defects than the previously isolated point mutation, including slow growth. Genetic and molecular evidence suggested that SNF6 is functionally related to the SNF2 and SNF5 genes. These genes may function together to affect transcription. PMID- 2188094 TI - p180, a novel recycling transmembrane glycoprotein with restricted cell type expression. AB - A 180-kilodalton (kDa) protein (p180) was identified among the antigens for a panel of monoclonal antibodies raised against human fibroblast cell surface proteins. Binding studies with 125I-Fab' fragments of an anti-p180 monoclonal antibody demonstrated that 10 to 30% of p180 was located on the plasma membrane and that the remaining 70 to 90% was on intracellular membranes. p180 was rapidly internalized from the cell surface at 37 degrees C, and kinetic analyses indicated that this was a constitutive process followed by the recycling of p180 back to the plasma membrane. Morphological studies demonstrated that on the cell surface p180 was concentrated in coated pits, whereas inside the cell it was found in endosomes as suggested by its colocalization with the transferrin receptor. Immunoblot analysis with a polyclonal antiserum raised against purified human protein showed that p180 has a restricted distribution with expression at high levels in fibroblast cultures and in tissues containing cells of mesodermal origin. A biochemical characterization of p180 showed it to be a transmembrane glycoprotein with an extracellular domain, which consists of approximately 30 kDa of complex oligosaccharides attached to at least 45 kDa of the protein core. The cytoplasmic domain of p180 was found to contain a serine residue(s) that was phosphorylated both in vivo and in vitro by activated protein kinase C. p180 was purified by subjecting solubilized membrane proteins from a human osteosarcoma cell line to immunoaffinity chromatography and gel filtration. The N-terminal sequence information obtained from the purified protein showed no homology to other known proteins. It was concluded that p180 may be a novel recycling receptor which is highly restricted in its expression to fibroblastlike cells. PMID- 2188095 TI - Coding and noncoding sequences at the 3' end of yeast histone H2B mRNA confer cell cycle regulation. AB - Yeast (Saccharomyces cerevisiae) histone mRNA synthesis is tightly regulated to the S phase of the cell division cycle as a result of both transcriptional and posttranscriptional regulation. We focused on the role of posttranscriptional control in histone H2B1 gene (HTB1) regulation and studied a portion of the HTB1 message required for cell-cycle-specific accumulation. The 3' end of the HTB1 gene containing a 17-amino-acid coding sequence and entire noncoding sequence was fused to the bacterial neomycin phosphotransferase II gene (neo) under control of the GAL1 promoter. The expression of the endogenous and chimeric HTB1 genes was analyzed during the yeast cell cycle. As yeast cells entered a synchronous cell cycle following release from alpha-factor arrest, the level of GAL1-promoter controlled neo-HTB1 message increased approximately 12-fold during S phase and dropped to basal level when the cells left S phase. This indicates that the 3' end of the HTB1 mRNA is capable of conferring cycle-specific regulation on a heterologous message. Deletion analysis of the 3' end showed that the signal for cell cycle control of HTB1 mRNA includes contiguous coding and noncoding sequences surrounding the stop codon. This differs from the situation in mammalian cells, whose posttranscriptional regulation of histone genes is mediated through a short sequence containing a stem-loop structure near the very terminus of the untranslated 3' end. PMID- 2188096 TI - Alternative splicing of RNAs transcribed from the human c-myb gene. AB - An alternative splicing event in which a portion of the intron bounded by the vE6 and vE7 exons with v-myb homology is included as an additional 363-nucleotide coding exon (termed E6A or coding exon 9A) has been described for normal and tumor murine cells that express myb. We show here that this alternative splicing event is conserved in human c-myb transcripts. In addition, another novel exon (termed E7A or coding exon 10A) is identified in human c-myb mRNAs expressed in normal and tumor cells. Although the myb protein isoform encoded by murine E6A containing mRNA is larger than the major c-myb protein, the predicted products of both forms of human alternatively spliced myb transcripts are 3'-truncated myb proteins that terminate in the alternative exons. These proteins are predicted to lack the same carboxy-terminal domains as the viral myb proteins encoded by avian myeloblastosis virus and E26 virus. The junction sequences that flank these exons closely resemble the consensus splice donor and splice acceptor sequences, yet the alternative transcripts are less abundant than is the major form of c-myb transcripts. The contribution that alternative splicing events in c-myb expression may make on c-myb function remains to be elucidated. PMID- 2188097 TI - The carboxy-terminal domains of erbB-2 and epidermal growth factor receptor exert different regulatory effects on intrinsic receptor tyrosine kinase function and transforming activity. AB - The erbB-2 gene product, gp185erbB-2, displays a potent transforming effect when overexpressed in NIH 3T3 cells. In addition, it possesses constitutively high levels of tyrosine kinase activity in the absence of exogenously added ligand. In this study, we demonstrate that its carboxy-terminal domain exerts an enhancing effect on erbB-2 kinase and transforming activities. A premature termination mutant of the erbB-2 protein, lacking the entire carboxy-terminal domain (erbB-2 delta 1050), showed a 40-fold reduction in transforming ability and a lowered in vivo kinase activity for intracellular substrates. When the carboxy-terminal domain of erbB-2 was substituted for its analogous region in the epidermal growth factor receptor (EGFR) (EGFR/erbB-2COOH chimera), it conferred erbB-2-like properties to the EGFR, including transforming ability in the absence of epidermal growth factor, elevated constitutive autokinase activity in vivo and in vitro, and constitutive ability to phosphorylate phospholipase C-gamma. Conversely, a chimeric erbB-2 molecule bearing an EGFR carboxy-terminal domain (erbB-2/EGFRCOOH chimera) showed reduced transforming and kinase activity with respect to the wild-type erbB-2 and was only slightly more efficient than the erbB-2 delta 1050 mutant. Thus, we conclude that the carboxy-terminal domains of erbB-2 and EGFR exert different regulatory effects on receptor kinase function and biological activity. The up regulation of gp185erbB-2 enzymatic activity exerted by its carboxy-terminal domain can explain, at least in part, its constitutive level of kinase activity. PMID- 2188098 TI - Mutant alcohol dehydrogenase (ADH III) presequences that affect both in vitro mitochondrial import and in vitro processing by the matrix protease. AB - Point mutations in the presequence of the mitochondrial alcohol dehydrogerase isoenzyme (ADH III) have been shown to affect either the import of the precursor protein into yeast mitochondria in vivo or its processing within the organelle. In the present work, the behavior of these mutants during in vitro import into isolated mitochondria was investigated. All point mutants tested were imported with a slower initial rate than that of the wild-type precursor. This defect was corrected when the precursors were treated with urea prior to import. Once imported, the extent of processing to the mature form of mutant precursors varied greatly and correlated well with the defects observed in vivo. This result was not affected by prior urea treatment. When matrix extracts enriched for the processing protease were used, this defect was shown to be due to failure of the protease to efficiently recognize or cleave the presequence, rather than to a lack of access to the precursor. The rate of import of two ADH III precursors bearing internal deletions in the leader sequence was similar to those of the point mutants, whereas a deletion leading to the removal of the 15 amino-terminal amino acids was poorly imported. The mature amino terminus of wild-type ADH III was determined to be Gln-25. Mutant m01 (Ser-26 to Phe), which reduced the efficiency of cleavage in vitro by 80%, was cleaved at the correct site. PMID- 2188099 TI - Complementary transcripts from two genes necessary for normal meiosis in the yeast Saccharomyces cerevisiae. AB - The SPO12 gene, which is required for meiosis I chromosome division during sporulation of the yeast Saccharomyces cerevisiae, has been isolated. DNA sequencing has identified an open reading frame of 173 codons that encodes the putative SPO12 protein and has no significant sequence similarities to known genes. The last 15 amino acids of this putative protein have a high negative charge, which appears to be required for function. A second sporulation-specific gene, designated SPO16, was found adjacent to SPO12 and shown to be necessary for efficient spore formation. The two genes are encoded on opposite DNA strands with only 103 nucleotides between the termination codons. Up to 700 nucleotides of the SPO12 and SPO16 transcripts are complementary, and the 3' untranslated region of the longest SPO16 transcript is complementary to all or nearly all of the SPO12 mRNA. A strain homozygous for an insertion which removes the complementarity between the SPO12 and SPO16 mRNAs has an efficiency of sporulation, number of spores per ascus, and spore viability identical to those of a wild-type strain. The complementarity therefore has either no function or only a subtle function in meiosis and sporulation. PMID- 2188100 TI - Identification of positive-acting domains in GCN2 protein kinase required for translational activation of GCN4 expression. AB - GCN4 is a transcriptional activator of amino acid-biosynthetic genes in the yeast Saccharomyces cerevisiae. GCN2, a translational activator of GCN4 expression, contains a domain homologous to the catalytic subunit of eucaryotic protein kinases. Substitution of a highly conserved lysine residue in the kinase domain abolished GCN2 regulatory function in vivo and its ability to autophosphorylate in vitro, indicating that GCN2 acts as a protein kinase in stimulating GCN4 expression. Elevated GCN2 gene dosage led to derepression of GCN4 under nonstarvation conditions; however, we found that GCN2 mRNA and protein levels did not increase in wild-type cells in response to amino acid starvation. Therefore, it appears that GCN2 protein kinase function is stimulated posttranslationally in amino acid-starved cells. Three dominant-constitutive GCN2 point mutations were isolated that led to derepressed GCN4 expression under nonstarvation conditions. Two of the GCN2(Con) mutations mapped in the kinase domain itself. The third mapped just downstream from a carboxyl-terminal segment homologous to histidyl tRNA synthetase (HisRS), which we suggested might function to detect uncharged tRNA in amino acid-starved cells and activate the adjacent protein kinase moiety. Deletions and substitutions in the HisRS-related sequences and in the carboxyl terminal segment in which one of the GCN2(Con) mutation mapped abolished GCN2 positive regulatory function in vivo without lowering autophosphorylation activity in vitro. These results suggest that sequences flanking the GCN2 protein kinase moiety are positive-acting domains required to increase recognition of physiological substrates or lower the requirement for uncharged tRNA to activate kinase activity under conditions of amino acid starvation. PMID- 2188101 TI - Analysis of Saccharomyces cerevisiae his3 transcription in vitro: biochemical support for multiple mechanisms of transcription. AB - The promoter region of the Saccharomyces cerevisiae his3 gene contains two TATA elements, TC and TR, that direct transcription initiation to two sites designated +1 and +13. On the basis of differences between their nucleotide sequences and their responsiveness to upstream promoter elements, it has previously been proposed that TC and TR promote transcription by different molecular mechanisms. To begin a study of his3 transcription in vitro, we used S. cerevisiae nuclear extracts together with various DNA templates and transcriptional activator proteins that have been characterized in vivo. We demonstrated accurate transcription initiation in vitro at the sites used in vivo, transcriptional activation by GCN4, and activation by a GAL4 derivative on various gal-his3 hybrid promoters. In all cases, transcription stimulation was dependent on the presence of an acidic activation region in the activator protein. In addition, analysis of promoters containing a variety of TR derivatives indicated that the level of transcription in vitro was directly related to the level achieved in vivo. The results demonstrated that the in vitro system accurately reproduced all known aspects of in vivo his3 transcription that depend on the TR element. However, in striking contrast to his3 transcription in vivo, transcription in vitro yielded approximately 20 times more of the +13 transcript than the +1 transcript. This result was not due to inability of the +1 initiation site to be efficiently utilized in vitro, but rather it reflects the lack of TC function in vitro. The results support the idea that TC and TR mediate transcription from the wild-type promoter by distinct mechanisms. PMID- 2188102 TI - U1 small nuclear RNA from Schizosaccharomyces pombe has unique and conserved features and is encoded by an essential single-copy gene. AB - We have cloned, sequenced, and disrupted the gene encoding U1 small nuclear RNA (snRNA) in the fission yeast Schizosaccharomyces pombe. This RNA is close in size and exhibits a high degree of secondary structure homology to human U1 RNA. There exist two regions of extended primary sequence identity between S. pombe and human U1 RNAs; the first comprises nucleotides involved in hydrogen bonding to 5' splice junctions, and the second is a single-stranded region which, in the human snRNA, forms part of the A protein binding site. S. pombe U1 lacks two nucleotides just following the 5' cap structure which are present in all other U1 homologs examined to date, and the region which corresponds to the binding site for the human 70K protein (molecular weight of 55,000) is more divergent than in other organisms. A putative upstream transcription signal is conserved in sequence and location among all loci encoding spliceosomal snRNAs in S. pombe with the exception of U6. Disruption of the single-copy U1 gene, designated snu1, reveals that this RNA is indispensable for viability. PMID- 2188104 TI - Mutations in Saccharomyces cerevisiae which confer resistance to several amino acid analogs. AB - Four new complementation groups of mutations which confer resistance to several amino acid analogs in Saccharomyces cerevisiae are described. These mutants were isolated on medium containing urea as the nitrogen source, in contrast to previous studies that had used medium containing proline. All four resistance to amino acid analog (raa) complementation groups appear to confer resistance by reducing amino acid analog and amino acid uptake. In some genetic backgrounds, raa leu2 and raa thr4 double mutants are inviable, even on rich medium. The raa4 mutation may affect multiple amino acid transport systems, since raa4 mutants are unable to use proline as a nitrogen source. raa4 is, however, unlinked to a previously described amino acid analog resistance and proline uptake mutant, aap1, or to the general amino acid permease mutant gap1. Both raa4 and gap1 prevent uptake of [3H]leucine in liquid cultures. The raa1, raa2, and raa3 mutants affect only a subset of the amino acid analogs and amino acids affected by raa4. The phenotypes of raa1, -2, and -3 mutants are readily observed on agar plates but are not seen in uptake and incorporation of amino acids measured in liquid media. PMID- 2188103 TI - GAL4 protein: purification, association with GAL80 protein, and conserved domain structure. AB - Expression of the yeast Saccharomyces cerevisiae GAL4 protein under its own (galactose-inducible) control gave 5 to 10 times the level of protein observed when the GAL4 gene was on a high-copy plasmid. Purification of GAL4 by a procedure including affinity chromatography on a GAL4-binding DNA column yielded not only GAL4 but also a second protein, shown to be GAL80 by its reaction with an antipeptide antibody. Sequence comparisons of GAL4 and other members of a family of proteins sharing homologous cysteine finger motifs identified an additional region of homology in the middle of these proteins shown by genetic analysis to be important for GAL4 function. GAL4 could be cleaved proteolytically at the boundary of the conserved region, defining internal and carboxy-terminal folded domains. PMID- 2188105 TI - Regulation of protein kinase C activity in neuronal differentiation induced by the N-ras oncogene in PC-12 cells. AB - Expression of the N-ras oncogene under the control of the glucocorticoid responsive promoter in the pheochromocytoma cell line UR61, a subline of PC-12 cells, has been used to investigate the differentiation process to neuronal cells triggered by ras oncogenes (I. Guerrero, A. Pellicer, and D. E. Burstein, Biochem. Biophys. Res. Commun. 150:1185-1192, 1988). Using ras-inducible cell lines, we observed that expression of the oncogenic N-ras p21 protein interferes with the ability of phorbol esters to induce downregulation of protein kinase C. This effect was associated with the appearance of immunologically detectable protein kinase C as well as the activity of the enzyme as analyzed either by binding of [3H]phorbol-12,13-dibutyrate in intact cells or by in vitro kinase activity. These results indicate a relationship between ras p21 and protein kinase C in neuronal differentiation in this model system. Comparison to the murine fibroblast system suggests that this relationship may be functional. PMID- 2188106 TI - The yeast KRE5 gene encodes a probable endoplasmic reticulum protein required for (1----6)-beta-D-glucan synthesis and normal cell growth. AB - Yeast kre mutants define a pathway of cell wall (1----6)-beta-D-glucan synthesis, and mutants in genes KRE5 and KRE6 appear to interact early in such a pathway. We have cloned KRE5, and the sequence predicts the product to be a large, hydrophilic, secretory glycoprotein which contains the COOH-terminal endoplasmic reticulum retention signal, HDEL. Deletion of the KRE5 gene resulted in cells with aberrant morphology and extremely compromised growth. Suppressors to the KRE5 deletions arose at a frequency of 1 in 10(7) to 1 in 10(8) and permitted an analysis of deletions which were found to contain no alkali-insoluble (1----6) beta-D-glucan. These results indicate a role for (1----6)-beta-D-glucan in normal cell growth and suggest a model for sequential assembly of (1----6)-beta-D-glucan in the yeast secretory pathway. PMID- 2188107 TI - Chromosomal destabilization during gene amplification. AB - Acentric extrachromosomal elements, such as submicroscopic autonomously replicating circular molecules (episomes) and double minute chromosomes, are common early, and in some cases initial, intermediates of gene amplification in many drug-resistant and tumor cell lines. In order to gain a more complete understanding of the amplification process, we investigated the molecular mechanisms by which such extrachromosomal elements are generated and we traced the fate of these amplification intermediates over time. The model system consists of a Chinese hamster cell line (L46) created by gene transfer in which the initial amplification product was shown previously to be an unstable extrachromosomal element containing an inverted duplication spanning more than 160 kilobases (J. C. Ruiz and G. M. Wahl, Mol. Cell. Biol. 8:4302-4313, 1988). In this study, we show that these molecules were formed by a process involving chromosomal deletion. Fluorescence in situ hybridization was performed at multiple time points on cells with amplified sequences. These studies reveal that the extrachromosomal molecules rapidly integrate into chromosomes, often near or at telomeres, and once integrated, the amplified sequences are themselves unstable. These data provide a molecular and cytogenetic chronology for gene amplification in this model system; an early event involves deletion to generate extrachromosomal elements, and subsequent integration of these elements precipitates a cascade of chromosome instability. PMID- 2188109 TI - Characterization of chicken c-ski oncogene products expressed by retrovirus vectors. AB - We constructed replication-competent avian retrovirus vectors that contain two of the three known types of chicken c-ski cDNAs and a third vector that contains a truncated c-ski cDNA. We developed antisera that recognize the c-ski proteins made by the three transforming c-ski viruses. All three proteins (apparent molecular masses, 50, 60, and 90 kilodaltons) are localized primarily in the nucleus. The proteins are differentially phosphorylated; immunofluorescence also suggests that there are differences in subnuclear localization of the c-ski proteins and that c-ski protein is associated with condensed chromatin in dividing cells. PMID- 2188108 TI - Transformation of chicken embryo fibroblast cells by avian retroviruses containing the human Fyn gene and its mutated genes. AB - The transforming activity of the human fyn protein, p59fyn, which is a kinase of the src family, was investigated by testing the effect of recombinant avian retrovirus (Fyn virus) expressing p59fyn on chickens or cultured chicken embryo fibroblast (CEF) cells. The Fyn virus did not induce transformed foci. After several passages of the virus stock on CEF cells, however, a few foci were detected in the presence of dimethyl sulfoxide. Chickens inoculated with Fyn virus at the stage of 12-day-old embryos developed fibrosarcomas 3 to 6 weeks after hatching. The viruses obtained from these foci and from one of the tumor tissues showed high transforming activity in the presence of dimethyl sulfoxide, suggesting that these viruses carry spontaneous mutations of the fyn gene. Four fyn genes from CEF DNAs infected with transforming viruses were molecularly cloned, and their products were confirmed to possess transforming activity. DNA sequence analysis of the fyn genes showed that two of the four mutants have Thr instead of Ile at position 338 in the kinase domain. The other two mutants carry deletions of 78 and 108 base pairs, respectively, which result in complete loss of region C of SH2. The overall level of proteins containing phosphotyrosine was significantly higher in transformed cells than in normal CEF cells. Our data indicate that when expressed at high levels in a retrovirus, normal p59fyn cannot cause cellular transformation, but that mutant p59fyn with either a single amino acid substitution in the kinase domain or a deletion including region C produces a transforming protein, perhaps due to enhanced tyrosine kinase activity. This is the first observation that deletion of region C can unmask the potential transforming activity of a src family kinase. PMID- 2188110 TI - Sequence and functional analysis of the positively acting regulatory gene amdR from Aspergillus nidulans. AB - The positively acting regulatory gene amdR of Aspergillus nidulans coordinately regulates the expression of five structural genes involved in the catabolism of certain amides (amdS), omega amino acids (gatA and gabA), and lactams (lamA and lamB) in the presence of omega amino acid inducers. Analysis of the amdR gene showed that it contains three small introns, heterogeneous 5' and 3' transcription sites, and multiple AUG codons prior to the major AUG initiator. The predicted amdR protein sequence has a cysteine-rich "zinc finger" DNA-binding motif at the amino-terminal end, four putative acidic transcription activation motifs in the carboxyl-terminal half, and two sequences homologous to the simian virus 40 large T antigen nuclear localization motif. These nuclear localization sequences overlap the cysteine-rich DNA-binding motif. A series of 5', 3', and internal deletions were examined in vivo for transcription activator function and showed that the amdR product contains at least two activation regions in the carboxyl-terminal half. Each of these activator amdR product contains at least two activation regions in the carboxyl-terminal half. Each of these activator regions may function independently, but both are required for wild-type levels of transcription activation. A number of the amdR deletion products were found to compete with the wild-type amdR product in vivo. Development of a rapid method for the localization of amdR mutations is presented, and using this technique, we localized and sequenced the mutation in the semiconstitutive amdR6c allele. The amdR6c missense mutation occurs in the middle of the gene, and it is suggested that it results in an altered protein which activates gene expression efficiently in the absence of an inducer. PMID- 2188111 TI - A and T homopolymeric stretches mediate a DNA inversion in Plasmodium falciparum which results in loss of gene expression. AB - Ring-infected erythrocyte surface antigen-negative isolates of Plasmodium falciparum demonstrate a complex DNA rearrangement with inversion of 5' coding sequences, deletion of upstream and flanking sequences, and healing of the truncated chromosome by telomere addition. An inversion intermediate that results in the telomeric gene structure for RESA has been identified in the pathway. This inversion creates a mitotically stable substrate for the sequence-specific addition of telomere repeats at the deletion breakpoint. PMID- 2188112 TI - The Saccharomyces cerevisiae DNA repair gene RAD2 is regulated in meiosis but not during the mitotic cell cycle. AB - The expression of the RAD2 gene of Saccharomyces cerevisiae is elevated upon DNA damage. Here, we show that RAD2 transcript levels also rise approximately eightfold during meiosis but remain constant during the mitotic cell cycle. The period of maximal RAD2 mRNA accumulation during meiosis is consistent with a possible role of RAD2 in a late stage of recombination, in mismatch repair of heteroduplexes, or both. PMID- 2188113 TI - Transcriptional regulation of SSA3, an HSP70 gene from Saccharomyces cerevisiae. AB - The SSA3 gene of Saccharomyces cerevisiae, a member of the HSP70 multigene family, is expressed at low levels under optimal growth conditions and is dramatically induced in response to heat shock. Sequences coinciding with two overlapping heat shock elements, located 156 base pairs upstream of the transcribed region, were necessary and sufficient for regulation of heat induction. The SSA3 promoter was also activated in an ssa1ssa2 double-mutant strain. This increase in the expression of SSA3 was mediated via the same upstream activating sequences that activated transcription in response to heat shock. PMID- 2188115 TI - The steroid receptor superfamily: more excitement predicted for the future. PMID- 2188114 TI - Lack of introns in the ribosomal protein gene S14 of trypanosomes. AB - Introns are almost always present in ribosomal protein genes, even in organisms in which introns are rare. Although trans spliced, the trypanosome ribosomal protein gene S14 apparently does not have cis introns, which supports the notion that such introns are absent in this organism. PMID- 2188116 TI - Expression of murine renin genes during fetal development. AB - Fetuses were examined to produce a developmental profile of renin expression in the kidneys and adrenal glands in single renin gene and two renin gene strains of mice. Sites of renin expression were detected by in situ hybridization using an 35S-labeled antisense RNA probe complimentary to the renin cDNA. Accumulation of renin transcripts in the adrenal gland reached a maximum at 15.5 days post coitum for all strains examined, but declined to undetectable levels by birth in one gene strains, while in two gene strains, the levels of renin transcripts lessened and by birth became limited to the developing inner cortex. Kidney renin transcripts were first detected at 14.5 days post coitum in the newly developing arteries in fetuses of both genotypes of mice. As the renal arterial tree developed, renin mRNA containing cells were progressively localized to more distal blood vessels and finally to the specialized cells of the afferent arteriole (juxtaglomerular cells). These results were confirmed by examining the localization of immunoreactive T antigen in transgenic fetuses. These mice carried a transgene which placed the SV40 T antigen structural gene under control of renin regulatory elements. Expression of T antigen occurred at the same sites in the kidneys and adrenal glands as renin mRNA. Furthermore, in strains with two renin genes, primer extension analysis indicated transcripts from both genes were present in equal proportion in combined kidney and adrenal gland extracts of total RNA. These transcripts were full length in size. The transient localization of renin mRNA in cells of the fetal intrarenal arteries is consistent with the notion that renin may be a useful marker for the developing renal vasculature. PMID- 2188117 TI - Identification of a ligand-binding region of the human insulin receptor encoded by the second exon of the gene. AB - Structure-function studies of the insulin molecule indicate that an insulin B chain domain comprising residues 22-26 is involved both in binding to the insulin receptor (INSR) and in insulin dimer formation, suggesting that this domain might also interact with a structure resembling the insulin dimer interface in the INSR. Expression of a mutant INSR cDNA with a deletion of the region corresponding to exon 2 of the INSR gene produces a protein devoid of insulin binding activity, although the mutant protein is processed appropriately to alpha and beta-subunits, suggesting that the insulin-binding domain is encoded at least in part by exon 2. Within this region of the INSR molecule, the sequence 83 103 fulfills the structural criteria for a dimer interface. Studies of mutant INSRs with substitutions for phenylalanine 88 or 89 show that the presence of phenylalanine at position 89 is essential for full binding affinity. PMID- 2188118 TI - Isolation and characterization of the human gonadotropin-releasing hormone gene in the hypothalamus and placenta. AB - The GnRH gene has been cloned in several species, but the location of the promoter and the exact start of transcription have not previously been determined. To characterize the low abundance human GnRH mRNA in the hypothalamus and placenta, we have employed the polymerase chain reaction. The hypothalamus was found to have a 61-base pair first exon, and its transcriptional start site was determined. The human hypothalamic GnRH cDNAs isolated thus far have all contained a short 5' untranslated region which would correspond to this start site. However, all human placental GnRH cDNAs reported to date have a long 5' untranslated region, which extends more than 140-base pairs 5' to this start site in the hypothalamus, suggesting the utilization of an alternative promoter in the placenta. In addition, the human GnRH gene undergoes differential splicing in these tissues. The first intron is removed from the hypothalamic, but retained in the placental, GnRH mRNA. Thus, the placenta has a very long first exon, while the hypothalamus has a comparatively short first exon, followed by a long first intron. This characterization of the human GnRH gene will now allow hormonal regulatory studies to be performed using gene transfer techniques. PMID- 2188119 TI - The role of germline gene expression and somatic mutation in the generation of autoantibodies to DNA. AB - Several distinctive features of anti-DNA autoantibodies have been identified by a detailed analysis of the available heavy and light chain sequences. They include unique VH gene segments that are not normally expressed in antibodies to external antigens, somatic mutations which may serve to change the antigenic specificity as well as to increase affinity, a less stringent choice of light chains, and a unique basic peptide in the heavy chain CDR3. It is proposed that in the majority of cases, the regulatory mechanism of self-tolerance in the healthy animal operates via VH gene expression to prevent the synthesis of potentially high affinity anti-DNA autoantibodies. PMID- 2188120 TI - A constitutive O6-methylguanine-DNA methyltransferase of Rhizobium meliloti. AB - We have identified a DNA methyltransferase activity of the nitrogen-fixing bacterium, Rhizobium meliloti, that repairs O6-methylguanine lesions. Repair of the O6-methylguanine residue results in transfer of the methyl group to a cysteine residue of a 28,000-dalton protein. The O6-methyltransferase activity is expressed constitutively and R. meliloti does not exhibit an adaptive response to alkylating agents. PMID- 2188121 TI - Endogenous mutagens derived from amino acids. AB - L-Cysteine, glutathione and the therapeutically used L-cysteine precursor, N acetyl-L-cysteine, induced strong mutagenic effects in Salmonella typhimurium (reversion of the his- strains TA97, TA92 and TA104), when tested in the presence of subcellular kidney preparations. The tyrosine metabolites, levodopa (an ortho hydroquinone) and homogentisic acid (a para-hydroquinone) reverted various his- strains as well. This mutagenicity did not require the presence of mammalian enzymes, and was relatively weak. The induction of gene mutations was also studied in mammalian cells (V79 Chinese hamster cells), using acquisition of resistance toward 6-thioguanine as the marker. L-Cysteine and N-acetyl-L-cysteine were found to be inactive, levodopa was weakly mutagenic, and homogentisic acid was strongly mutagenic (enhancing the mutation frequency 135-fold above background at an exposure concentration of 50 microM). This finding is striking as the urinary concentration of homogentisic acid is about 1000 times higher in patients with a genetic defect in homogentisic acid 1,2-dioxygenase (alkaptonuria). Genotoxic and carcinogenic effects of other amino acids and metabolites, reported in the literature, are discussed as well. PMID- 2188122 TI - Age-related DNA modifications (I-compounds): modulation by physiological and pathological processes. AB - I-compounds are covalent DNA modifications that can be detected and measured by 32P-postlabeling assay because of their DNA-adduct like properties. They accumulate in an age-dependent, highly reproducible manner in tissue DNA of untreated animals in the absence of exogenous carcinogens and, therefore, appear to arise via the interaction of DNA with endogenous reactants formed in the course of normal metabolism. Chromatographically, they exhibit a wide range of polarities, indicative of structural diversity. In addition to age-dependent increases, I-compound profiles exhibit prominent species-, sex-, tissue- and diet dependent qualitative and quantitative differences. Natural-ingredient (chow) diets produce qualitative differences as well as substantially higher I-compound levels in rat liver and kidney, when compared with purified diets. Modified purified diets containing high carbohydrate, protein, or fat concentrations further modulate I-compound profiles. During liver regeneration, I-compounds behave like DNA adducts rather than m5 C in that their levels are not quickly restored. Treatment of rats with the hepatocarcinogens 2,3,7,8-tetrachlorodibenzo p-dioxin (TCDD), CCl4, and peroxisome proliferators as well as with a choline devoid hepatocarcinogenic diet depressed the age-related increases of I-compound levels in liver, the target organ. Additional 32P-labeled derivatives were observed only with the peroxisome proliferators and presumably represent DNA adducts of exogenous origin. No I-compounds were detected in a series of Morris hepatomas with different degrees of differentiation. Thus, loss of I-compounds may be associated with altered gene expression/dedifferentiation. On the other hand, the age-dependent accumulation of I-compounds and their adduct-like character suggest potential relations to aging-associated dysdifferentiation and initiation of cancer. Structural complexity indicates different biological roles of I-compounds. PMID- 2188124 TI - Spontaneous deamination of cytosine and 5-methylcytosine residues in DNA and replacement of 5-methylcytosine residues with cytosine residues. PMID- 2188123 TI - Exposure of humans to endogenous N-nitroso compounds: implications in cancer etiology. AB - Two sensitive procedures to quantitate human exposure to endogenous N-nitroso compounds (NOC) and/or methylating agents have been developed. One, the NPRO test, is based on the excretion of N-nitrosoproline (NPRO) and other N nitrosoamino acids in the urine, that are measured as an index of endogenous nitrosation, following ingestion of precursors. The NPRO test has been applied to human subjects in clinical and epidemiological studies, and the kinetics and dietary modifiers of endogenous nitrosation have been investigated. Results obtained after application of the NPRO test to subjects at high risk for cancers of the stomach, esophagus, oral cavity and urinary bladder are summarized. In most instances, higher exposures to endogenous NOC were found in high-risk subjects, but individual exposure was greatly affected by dietary modifiers or disease state. Vitamin C efficiently lowered the body burden of intragastrically formed NOC. In experimental animals 3-methyladenine (3-MeAde) is excreted in urine following exposure to methylating NOC. Humans normally excrete 3-MeAde, the origin of which remains unknown. Recently developed analytical methodology permits large numbers of human urine samples to be analyzed and a wide variation is observed. Preliminary results suggest a weak correlation between basal NPRO excretion and background 3-MeAde excretion. Taken together, the results point to an etiological role of endogenously formed NOC in certain human cancers, and provide an interpretation of epidemiological findings that have shown protective effects of fruits and vegetables against several malignancies. PMID- 2188125 TI - Endogenous genotoxic agents and processes as a basis of spontaneous carcinogenesis. AB - A list of endogenous DNA-damaging agents and processes is given. Endogenous electrophiles are found with the cosubstrates of physiological transfer reactions (S-adenosylmethionine for methylation, ATP for phosphorylation, NAD+ for ADP ribosylation, acetyl CoA for acetylation). Aldehyde groups (glyceraldehyde-3 phosphate, formaldehyde, open forms of reducing sugars, degradation products of peroxidation) or alkylating degradation products derived from endogenous nitroso compounds represent additional possibilities. Radical-forming reactions include leakage of the superoxide anion radical from terminal cytochromes and redox cycles, hydroxyl radical formation by the Fenton reaction from endogenous hydrogen peroxide, and the formation of lipid peroxides. Genetic instability by spontaneous deaminations and depurinations as well as replicative instability by tautomer errors and in the presence of mutagenic metal ions represent a third important class of endogenous genotoxic processes. The postulated endogenous genotoxicity could form the mechanistic basis for what is called 'spontaneous' tumor incidence and explain the possibility of an increased tumor incidence after treatment of animals with non-genotoxic compounds exhibiting tumor-promoting activity only. Individual differences are expected to be seen also with endogenous DNA damage. The presence of endogenous DNA damage implies that exogenous DNA-carcinogen adducts give rise to an incremental damage which is expected to be proportional to the carcinogen dose at lowest levels. An increased tumor risk due to exposure to exogenous genotoxic carcinogens could therefore be assessed in terms of the background DNA damage, for instance in multiples of the mean level or of the interindividual variability in a population. PMID- 2188126 TI - Errors in DNA synthesis: a source of spontaneous mutations. AB - Spontaneous mutations in somatic cells may engender several pathologic processes, including cancer. The sources of these mutations remain to be established. We present a conceptual framework in which to analyze the sources of spontaneous mutations and focus here on 3 endogenous processes that have the potential to generate spontaneous sequence alterations in DNA. These are: replication errors, depurination of DNA, and damage to DNA by the generation of active-oxygen species. Each of these processes occurs more frequently than the rate of mutagenesis in somatic cells, but are repaired by different and overlapping mechanisms. Model systems are being developed to determine the spectrum of mutations produced by each of these processes in vitro. A comparison of these spectra with the overall spectrum of spontaneous mutations in somatic cells may help to determine the contribution of each of these processes to spontaneous mutation. PMID- 2188127 TI - Bile flow and colon cancer. PMID- 2188128 TI - Interest of biotyping Candida albicans in chronic vulvovaginitis. AB - Chronic vulvovaginitis due to Candida albicans is a major clinical problem for the physician. Although new antifungal drugs are now available, the therapeutic approach of this disease remains disappointing. The aims of this study were two fold. First, we wanted to evaluate the reliability of a single sampling performed by most clinicians in verifying if the yeast infects the entire genital mucosa or a preferential site and, second, to biotype the strains recovered in order to see if more than one strain are responsible for the infection. We found, in 18 patients suffering from vaginal candidosis, that the entire genital mucosa was infected by the yeast and the strain recovered from the different genital sites in a single patient was the same in 100% of the cases. Only 1.4% of the samples were negative. In addition, we biotyped the strains obtained from the gastrointestinal tract of these patients to evaluate this site as a potential source of infection. We obtained gastrointestinal tract samples for 15 of the 18 patients and we could identify C. albicans in 100% of the cases. Furthermore, 73.3% of the patients harboured the same strains of C. albicans in the gastrointestinal tract as in the vagina. PMID- 2188130 TI - Congress moves to regulate self-referral and physicians' ownership of clinical laboratories. PMID- 2188129 TI - Activation of coagulation after administration of tumor necrosis factor to normal subjects. AB - Tumor necrosis factor has been implicated in the activation of blood coagulation in septicemia, a condition commonly associated with intravascular coagulation and disturbances of hemostasis. To evaluate the early dynamics and the route of the in vivo coagulative response to tumor necrosis factor, we performed a controlled study in six healthy men, monitoring the activation of the common and intrinsic pathways of coagulation with highly sensitive and specific radioimmunoassays. Recombinant human tumor necrosis factor, administered as an intravenous bolus injection (50 micrograms per square meter of body-surface area), induced an early and short-lived rise in circulating levels of the activation peptide of factor X, reaching maximal values after 30 to 45 minutes (mean +/- SEM increase after 45 minutes, 34.2 +/- 18.2 percent; tumor necrosis factor vs. saline, P = 0.015). This was followed by a gradual and prolonged increase in the plasma concentration of the prothrombin fragment F1+2, peaking after four to five hours (mean increase after five hours, 348.0 +/- 144.8 percent; tumor necrosis factor vs. saline, P less than 0.0001). These findings signify the formation of factor Xa (activated factor X) and the activation of prothrombin. Activation of the intrinsic pathway could not be detected by a series of measurements of the plasma levels of factor XII, prekallikrein, factor XIIa-C1 inhibitor complexes, kallikrein-C1 inhibitor complexes, and the activation peptide of factor IX. The delay between the maximal activation of factor X and that of prothrombin amounted to several hours, indicating that neutralization of factor Xa activity was slow. We conclude that a single injection of tumor necrosis factor elicits a rapid and sustained activation of the common pathway of coagulation, probably induced through the extrinsic route. Our results suggest that tumor necrosis factor could play an important part in the early activation of the hemostatic mechanism in septicemia. PMID- 2188131 TI - Multifocal atrial tachycardia. PMID- 2188132 TI - Mad cows and the minister. PMID- 2188133 TI - World Health Organization--new man takes over. PMID- 2188134 TI - Crystallography. Following proteins in time. PMID- 2188135 TI - Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle. AB - Dystrophin, the protein encoded by the Duchenne muscular dystrophy (DMD) gene, exists in a large oligomeric complex. We show here that four glycoproteins are integral components of the dystrophin complex and that the concentration of one of these is greatly reduced in DMD patients. Thus, the absence of dystrophin may lead to the loss of a dystrophin-associated glycoprotein, and the reduction in this glycoprotein may be one of the first stages of the molecular pathogenesis of muscular dystrophy. PMID- 2188136 TI - Genetic organization of a chimpanzee lentivirus related to HIV-1. AB - Simian immunodeficiency viruses have been isolated from four species of monkey, the 'captive' macaque and mangabey and the 'feral' African green monkey and mandrill. While none of these viruses is a replica of HIV-1, the macaque and mangabey viruses represent correct genetic models for HIV-2, possessing exactly the same complement of genes. Recently a lentivirus has been identified in two wild chimpanzees (Pan troglodytes troglodytes) in Gabon, west equatorial Africa, and isolated from one of them. This virus is referred to as SIVCPZ. Sera from these animals cross reacted with all the HIV-1 proteins including the envelope glycoproteins. Here, we describe the molecular cloning and sequencing of an infectious proviral clone of SIVCPZ. The overall genetic organization was the same as that of HIV-1, but phylogenetic analysis revealed that the sequence was more divergent than any HIV-1 sequence reported so far. The vpu gene product, found only in the type 1 viruses, was particularly different (64% divergent to HIV-1BRU) suggesting that the SIVCPZ represents a distinct subtype. These findings indicate that there is a larger pool of simian lentiviruses than previously suspected and revives debate as to the origins of HIV-1. PMID- 2188137 TI - How different eukaryotic transcriptional activators can cooperate promiscuously. AB - A striking characteristic of many different eukaryotic transcriptional activators is their ability to activate gene expression synergistically. Thus, for example, the rat glucocorticoid receptor and the yeast activator GAL4 cooperatively activate transcription of a mammalian gene bearing binding sites for each of the proteins: activation by both activators is greater than the sum of the effects of each working alone. It would seem unlikely that these two proteins from such different organisms directly interact; rather, the idea has been suggested that these and at least some other eukaryotic activators can work synergistically by simultaneously touching some part of the transcriptional machinery. An important prediction of this idea is that synergy between two such activators would be seen under conditions where each is present at concentrations sufficiently high to saturate its site on DNA. In this paper we use transcription in vitro to confirm that prediction using a derivative of the yeast activator GAL4 and the mammalian transcription factor ATF. The accompanying paper describes a similar conclusion comparing the effects of singly and multiply bound GAL4 molecules. PMID- 2188138 TI - Intracellular transport. Vesicular consumption. PMID- 2188139 TI - Epidemiology. Radon and the risks of cancer. PMID- 2188140 TI - Papain and related proteins. PMID- 2188141 TI - The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. AB - Mice homozygous for the recessive mutation osteopetrosis (op) on chromosome 3 have a restricted capacity for bone remodelling, and are severely deficient in mature macrophages and osteoclasts. Both cell populations originate from a common haemopoietic progenitor. As op/op mice are not cured by transplants of normal bone marrow cells, the defects in op/op mice may be associated with an abnormal haematopoietic microenvironment rather than with an intrinsic defect in haematopoietic progenitors. To investigate the molecular and biochemical basis of the defects caused by the op mutation, we established primary fibroblast cell lines from op/op mice and tested the ability of these cell lines to support the proliferation of macrophage progenitors. We show that op/op fibroblasts are defective in production of functional macrophage colony-stimulating factor (M CSF), although its messenger RNA (Csfm mRNA) is present at normal levels. This defect in M-CSF production and the recent mapping of the Csfm structural gene near op on chromosome 3 suggest that op is a mutation within the Csfm gene itself. We have sequenced Csfm complementary DNA prepared from op/op fibroblasts and found a single base pair insertion in the coding region of the Csfm gene that generates a stop codon 21 base pairs downstream. Thus, the op mutation is within the Csfm coding region and we conclude that the pathological changes in this mutant result from the absence of M-CSF. PMID- 2188142 TI - [100 years of lectin research--a balance]. AB - A hundred years of lectin research has led to the development of lectinology as an independent field of study. Although lectinology is in part related to immunology, fundamental differences exist. Lectins are important tools in biochemistry, histochemistry and clinical diagnosis. The essential in vivo function of lectins is to combine glycoconjugates. The function of lectins in microorganisms and in animals is partially known, whereas the function of lectins in plants is mostly unclear. Of special interest, now as before, are the toxic lectins of the ricin type consisting of an A-chain (N-glycosidase) and a B-chain (D-galactose-specific lectin). PMID- 2188143 TI - [Electron energy loss spectroscopy (EELS) as a method for the localization of antigens and other substances in cells and tissues]. AB - The localization of antigens and other substances in cells and tissues by electron microscopy is usually performed by immunohistochemical techniques employing labelled conventional or monoclonal antibodies. For the ultrastructural localization of the antibodies, they are coupled to electron-dense labels like gold or ferritin. Here, we demonstrate a novel method to localize antigens in cells, tissues, and on other supports. By electron energy loss spectroscopy (EELS) it is possible to directly analyze the distribution of antigens, metabolites or other substances without the use of labelled antibodies: as an example we demonstrate the distribution of the immunomodulator lipopeptide in B lymphocytes and macrophages. EELS represents a novel, sensitive, and generally applicable method for the detection and localization of antigens and other substances in biology and medicine. PMID- 2188144 TI - Neurophysiological and behavioral development in birds: song learning as a model system. AB - The avian song system is a particularly good model for studying the behavioral and physiological aspects of animal development. One seemingly trivial but very important reason for this is that the sound spectrograph enables sounds to be described, measured and analyzed objectively and in detail. Secondly, birdsong is one of the few behaviors which is performed by a separate chain of brain regions and is therefore relatively easy to investigate neurophysiologically. Work on song also provides a clear illustration of the subtle way in which birds are influenced by their internal and external environments during development. PMID- 2188146 TI - Phylogeny of arthropod immunity. An inducible humoral response in the Kalahari millipede, Triaenostreptus triodus (Attems). PMID- 2188147 TI - National Institutes of Health Consensus Development Conference on Oral Complications of Cancer Therapies: Diagnosis, Prevention, and Treatment. Bethesda, Maryland, April 17-19, 1989. PMID- 2188145 TI - Evolving trends in steroid hormone receptor research. AB - Recent advances have challenged classical notions regarding the nature of steroid hormone receptors in the cell including localization, activation, configuration, and stability. Molecular biology has revealed a remarkable similarity in the primary structure of a wide variety of receptor classes that goes beyond steroid action. Post-translational modification of a primary unit, expressed in response to genetic conservatism, would appear to assure receptor dynamics specific to hormone-, organ-, and tissue-dependent processes, and may even lead to toxicity and oncogenicity. PMID- 2188148 TI - Oral complications of cancer therapies. Description and incidence of oral complications. AB - No part of the body reflects the complications of cancer chemotherapy as visibly and as vividly as the mouth. The infectious, hemorrhagic, cytotoxic, nutritional, and neurologic signs of drug toxicity are reflected in the mouth by changes in the color, character, comfort, and continuity of the mucosa. The stomatologic complications of radiotherapy for oral cancer are physical and physiological in nature, transient or lasting in duration, and reversible or irreversible in type. Some linger as permanent mementos long after the cancer has been destroyed. They stem from radiation injury to the salivary glands, oral mucosa, oral musculature, alveolar bone, and developing teeth. They are expressed clinically by xerostomia, trismus, radiation dermatitis, nutritional stomatitis, and dentofacial malformation. In both cancer chemotherapy and cancer radiotherapy, the oral complications vary in pattern, duration, intensity, and number, with not every patient developing every complication. PMID- 2188149 TI - Nursing management of acute oral complications of cancer. AB - This review evaluates the state of the science and art of nursing management of acute oral complications of cancer. Published general oral hygiene protocols are reviewed briefly, and modifications to routine nursing care for hemorrhage, infection, pain, and problems associated with radiation to the head and neck are explored. There is a scarcity of research on which to base recommendations. The literature is primarily anecdotal or based on reports of experience at a single institution. Inconsistencies among such reports are numerous and have a detrimental effect on nursing management, as various clinicians provide different patient care instruction. Known principles, e.g., the need for adequate plaque removal and infection control, form the basis for nursing guidelines. Research is needed to guide clinical decision making, especially in defining the use of toothbrush substitutes. Problems in pain management appear to arise from inadequate application of known pain management principles. Since many of the oral complications are interrelated, nursing management must also take an integrated approach, and nursing care research must be conducted in the context of multidisciplinary care. Careful transfer of current research-based knowledge to practice and future research will help to achieve high-quality nursing management of acute oral complications. PMID- 2188150 TI - Oral complications of cancer therapies. Oral complications in the pediatric population. AB - A number of acute oral complications may be associated with cancer therapy in children, but the extent and duration of these complications, and the most effective management techniques. have not been well described. The few studies differ in design, making comparisons difficult. Well-controlled, prospective clinical studies are needed to define the most effective strategies for the management of acute oral complications in children. However, it is clear that dental intervention prior to cancer therapy is an important factor in the optimal preparation of the patient. During cancer therapy, intensive supervised oral preventive protocols appear to be of benefit to the child's oral health, overall comfort, and well-being. Furthermore, the prevention of oral infection may significantly reduce the morbidity associated with cancer therapy. Long-term preventive oral care may help prevent dental disease and infection in medically compromised children and contribute to improving the quality of life. PMID- 2188151 TI - Recognition, incidence, and management of oral graft-versus-host disease. AB - Acute and chronic graft-versus-host disease (GVHD) are significant complications of allogeneic bone marrow transplantation that occur when immunologically active T-cell lymphocytes are transplanted into an immunosuppressed recipient who is genetically disparate from the marrow donor. Oral GVHD lesions closely resemble those seen with a number of autoimmune connective tissue disease, including lichen planus, systemic sclerosis, lupus erythematosus, and Sjogren's syndrome. Mucosal erythema, atrophy, and ulceration are noted clinically; lichen planus like lesions are the most distinctive oral lesions. Salivary gland changes include changes in both flow rate and sialochemistry. Oral involvement ranges between 33% and 75% for patients with acute GVHD and upwards of 80% for those with chronic GVHD. Management of oral GVHD lesions depends on successful systemic therapy, although topical steroids can be of help in some instances. PMID- 2188152 TI - Osteoradionecrosis: causes and prevention. AB - Osteoradionecrosis (ORN) is one of the most serious complications arising from head and neck radiation therapy. Current research has shown that ORN represents nonhealing, dead bone and is not a state of infection. ORN is the result of functional and structural bony changes that may not be expressed for months or years. ORN may occur spontaneously or in response to wounding. Predisposing factors include absorbed radiation dose, fractionation, delivery modality, and dental status. Timing of dental extractions and other factors have also been shown to affect incidence. ORN may be reduced through early intraoral evaluation, treatment, and adequate healing time prior to beginning RT. Hyperbaric oxygen (HBO) therapy has been beneficial in the prevention and treatment of ORN. It is of paramount importance for the medical community to recognize the factors that may reduce ORN incidence, endorse oral care protocols, and acknowledge the value of HBO therapy in the prevention and treatment of this disease. PMID- 2188154 TI - Oral complications of cancer therapies. Oral defenses and compromises: an overview. PMID- 2188153 TI - Implications of cancer therapy to the head and neck on growth and development and other delayed effects. AB - These studies of late effects related to cancer treatment to the head and neck demonstrate that these patients may develop a variety of abnormalities, the majority of which occur after irradiation. Once a child is "cured" of a primary malignant disorder, visits to oncologists usually continue but decrease in frequency. Regular visits to the dentist continue and are usually at least a biannual event. Attention to the details of the patient's previous medical history is of paramount importance if the delayed effects discussed here are to be suspected and recognized. Early diagnosis of thyroid and GH deficiencies and institution of appropriate hormone treatment may improve these children's growth and development. Recognition of cataracts and dry-eye syndrome is important to prevent visual difficulties. Careful oral examination and attention to the patient's general overall neurological presentation is an important adjunct to diagnosis of learning difficulties and early recognition of second tumors of the head and neck. PMID- 2188155 TI - Oral complications of cancer therapies. Chronic dental complications. AB - Radiation therapy (RT) and chemotherapy have increased long-term survival with certain cancers. The use of dental investigation and treatment of chronic or delayed oral complications is developing. Altered dental root development, enamel opacities, hypocalcifications, periodontal problems, and a higher caries rate are seen in children treated with chemotherapy. The psychosocial implications of long term survival on routine dental care are important. Prevention and treatment of long-term oral complications of radiation therapy are changing. Osteoradionecrosis remains complicated and devastating. Strategies that avoid post-RT extractions include caries prevention, oral hygiene measures, meticulous restorative dentistry, overdentures, and improved posts for endodontically treated teeth. Guidelines for post-RT extractions vary greatly. Pediatric patients who receive head and neck irradiation may have total arrest of tooth and jaw development within the portal. The dentist must be able to diagnose and treat the variety of alterations already identified and should engage in scholarly research to answer the questions that remain. PMID- 2188156 TI - Oral complications of cancer therapies. Infectious and noninfectious systemic consequences. AB - Oral complications of cancer therapy often have systemic consequences. Pain and discomfort are common and can lower intake of fluid and nutrients, which in severe cases can lead to dehydration and malnutrition, requiring hospitalization. Oral infections are frequent accompaniments of cancer treatment. Herpes simplex virus is the most common symptomatic oral viral infection, and, in latently infected patients the virus is frequently reactivated after cytoreductive therapy. Viral (infectious) oral mucositis is often indistinguishable from noninfectious mucositis. Bacterial infections are less commonly observed today, perhaps because of the routine use of empiric broad-spectrum antibiotics; however, many episodes of septicemia in neutropenic patients apparently originate from oral microorganisms. Fungal infections are frequent and are usually due to Candida species. Spread to the esophagus or systemic dissemination can occur. Noninfectious oral mucositis can be used as a marker of toxic effects in other organs, especially hepatic veno-occlusive disease. In bone marrow transplant patients with mucositis, hepatic veno-occlusive disease is six times more frequent than in such patients without mucositis. PMID- 2188157 TI - Consensus statement: oral complications of cancer therapies. National Institutes of Health Consensus Development Panel. PMID- 2188158 TI - Oral antimicrobial agents--chlorhexidine. AB - Chlorhexidine's structural characteristics give it potent antimicrobial activity, effectiveness at low concentrations, substantivity that prolongs its therapeutic effect in the oral environment, minimal resorption from the gastrointestinal tract, and the ability to reduce plaque. The use of this agent for oral stomatitis in neoplasia patients has recently been studied. Treatment-associated oral soft tissue inflammation and ulceration were significantly reduced by chlorhexidine in patients undergoing intensive chemotherapy. Reductions in total streptococci and yeast counts were also observed. When used in conjunction with systemic antifungal agents, such as nystatin or clotrimazole, a significantly decreased incidence of clinical oral candidiasis and Candida septicemia was observed. In contrast, in two studies in which high-dose head and neck radiation therapy was applied, there was no reduction in stomatitis. Oral gram-negative bacilli have been shown to increase in high-dose chemotherapy patients who are taking chlorhexidine during the treatment period (3 wk to 2 mo). However, no increase in systemic gram-negative infections or other adverse negative medical consequences were observed. This agent appears to be of therapeutic benefit in reduction of dental plaque, gingivitis, and stomatitis in the high-risk chemotherapy population when used in conjunction with other topical and systemic antimicrobial agents as prophylaxis. Although no toxic or serious adverse effects of chlorhexidine rinse have been observed in the short-term studies to date, the effects of longer-term chlorhexidine administration should be evaluated. PMID- 2188159 TI - Oral complications of cancer therapies. Pretherapy interventions to modify salivary dysfunction. AB - Salivary gland dysfunction is a common side effect of cancer therapies. Salivary secretions are reduced rapidly after starting head and neck radiotherapy. Salivary gland dysfunction has also been linked to bone marrow transplantation and to cytotoxic chemotherapy. Salivary gland stimulation during radiation has been suggested as a means of reducing radiation damage. Results of an ongoing study investigating the effects of pilocarpine on radiation-induced salivary gland dysfunction suggest that parotid function was preserved, but not submandibular/sublingual function. Also, patients receiving pilocarpine had less frequent oral complaints. Further research is necessary to develop means of preventing or alleviating the salivary side effects of cancer therapies. PMID- 2188160 TI - Oral complications of cancer therapies. Management of mucositis during therapy. AB - This paper reviews the purposes of an oral care protocol, the major components of an oral care regimen, and oral care protocols and studies done to date. Many questions remain in the area of optimal oral care for the patient experiencing mucositis as a sequela of cancer treatment. Research is needed on types and use of mouth rinses, effective, harmless, and pleasant lip lubricants, appropriate analgesic and anti-inflammatory combinations, and the effectiveness of a variety of devices for oral cleansing, to name a few areas. As outpatient oncology services grow, oral care protocols must be developed to meet the needs of ambulatory patient populations. Oral care regimens must be safe, easy to use, and economical as well as effective to ensure patient and staff compliance. Research on the management of mucositis must be conducted in both inpatient and outpatient settings. Finally, in order to obtain sufficient sample sizes and optimize data collection, these studies will need to be conducted by multidisciplinary teams (including dentists, oncologists, radiation therapists, and nurses) across multiple sites. Not until large-scale clinical trials are done on the treatment of mucositis will we be able to optimize the therapeutic regimen for the patient. PMID- 2188161 TI - Obstetrics--way back when! PMID- 2188162 TI - Relocating a patient care unit. AB - Nurse managers frequently are required to relocate patient care units in a hospital. Whether temporary or permanent, the move entails the same process: thorough planning, an interdisciplinary approach, and good communication among everyone involved. The stages of relocating a patient care unit are the preparation phase, the actual move, closing the old unit, and adjusting to the new unit. Of these, the preparation phase requires the most attention. The disciplines most involved with planning the relocation are nursing and hospital administration. Others that must be consulted are physicians, materials management, and housekeeping staffs. It is imperative that staff nurses be involved in the planning process early to promote staff adjustment to the relocation experience. The authors describe the phases of relocating a patient care unit and the details to be considered based on their experience at a gerontologic facility in a major medical center. PMID- 2188163 TI - The effect of second generation platinum cytostatics on mammalian cell proliferation. AB - The effect of three second generation platinum complexes on proliferation of tumor cells (HeLa, C6) and nontumor cells (LEP) was studied, and compared with that of cis-DDP. The highest activity, comparable with cis-DDP, was exhibited by oxoplatinum. CBDCA was somewhat less active in this system, but had a greater effect on both lines of tumor cells than on nontumor cells. Cell proliferation was inhibited least of all by CHIP(IV). The differences observed are discussed from the point of view of the structure and oxidation state of the platinum complexes. PMID- 2188164 TI - Humoral leukocyte adherence inhibition (H-LAI) test in screening of high risk group for lung cancer. AB - In the screening examinations of 150 ore miners the positive humoral immune response against lung tumor antigen was measured in 30 serum samples. Repeated testing of positive sera (after 1-3 years) was possible only in 15 cases. Among them, the reaction of 12 serum samples was again positive, and 2 persons died of lung cancer. The results obtained in these follow-up investigations are discussed. PMID- 2188165 TI - [Sublingually administered captopril versus nifedipine in hypertension emergencies]. AB - Aim of the study was to assess the effectiveness and tolerability of sublingual captopril (SLC) versus sublingual nifedipine (SLN) in treating hypertensive emergencies. During hypertensive crises (systolic blood pressure exceeding 200 mmHg and diastolic blood pressure exceeding 115 mmHg) forty hypertensive patients received either 25 mg of SLC or 10 mg of SLN in a randomized single blind fashion. Blood pressure and heart rate were then controlled after 5, 10, 15, 20, 30, 45, 60, 120 min. and, in 18 cases, up to the 8th hour from the administration. Our results showed: 1) a satisfactory control of the hypertensive crises in 80% of patients treated with SLC with a significant blood pressure reduction after 10 min. (13/8 mmHg, p less than 0.02), while the maximum hypotensive effect was achieved after 30 min. (52/36 mmHg, p less than 0.001); SLN was able to reduce blood pressure in 90% of all the cases, with a significant reduction after 5 min. (15/11 mmHg, p less than 0.02) and hypotensive peak after 20 min (57/38 mmHg, p greater than 0.001); 2) no significant differences for hypotensive effectiveness between the two groups, but with SLC having a mildly delayed onset of action when compared to SLN; 3) antihypertensive effect lasting for about 6 hours in patients treated with SLC and blood pressure progressively raising after 4 hours in patients who received SLN; 4) a significant correlation between blood pressure reduction and blood pressure before drug administration in both groups; a significant correlation between pretreatment PRA and antihypertensive effect in the SLC group. We conclude that both drugs are effective and useful in treating hypertensive emergencies. Anyway we think that in severe forms SLN should be preferred for the shorter time preceding onset of action. PMID- 2188166 TI - [Prostaglandins. Their biological effects and technics for their measurement]. AB - A careful survey of known biological effects of various prostaglandins and measurement techniques is made. Limitations and advantages of these techniques are also indicated. PMID- 2188167 TI - [Recent findings in the pathogenesis of bronchial asthma]. AB - The latest discoveries about the pathogenesis of asthma are reported with emphasis on new data concerning the discovery of factors capable of controlling the production of IgE antibodies. The mechanisms implicated in early and late phase reactions are then discussed. In addition, the relationships between neuropeptides and chronic inflammation are described. Finally, the role of active substances produced by the bronchial epithelium on the induction and maintenance of bronchial inflammation is reviewed. PMID- 2188168 TI - [The serum beta-2-microglobulin values in drug addicts with persistent generalized lymphadenopathy]. AB - Serum beta 2-microglobulin levels (beta-2-M) were studied in 150 drug addicts, 50 of them asymptomatic carriers of anti HIV-1 antibodies, 50 symptomatic carriers with persistent generalized lymphadenopathy (P.G.L.) and 50 serum negative patients who had been living in a closed community for at least 2 years. The results showed increased beta-2-M in 24 P.G.L. patients (48%), in 6 of the asymptomatic serum positive cases (12%) and in 3 of the serum negative subjects (6%). No such increase was found in the selected control group. Statistical analysis using the chi-square test and one-way variance analysis gave a significant result. The data suggest that increased serum beta-2-M is essentially linked to the presence of P.G.L. PMID- 2188169 TI - [The Boario project. A study of the prevalence of lithiasis in a spa population]. AB - In order to better evaluate some epidemiological findings observed during previous studies on large samples of free living populations we carried out a case-control study on a randomly selected group of subjects in a health spa, Boario Terme. Seven-hundred and thirty subjects, aged 40-69 years, participated in the study. The study protocol included an ultrasonographic examination of the upper abdomen, a physical examination, a questionnaire, and a blood sample. Prevalence of gallstone disease was two times higher in females (37.2%) than in males (19.7%) (RRMH = 1.88). Fifty out of the 80 gallstone subjects were not aware of the disease prior the study (62.5%), and 60 did not experience any specific biliary symptom (colic) in the 5 years prior the study. The so-called "nonspecific symptoms" were not found related to gallstone disease. Gallstone disease was positively related to number of pregnancies, obesity, and economical status. In conclusion the present study confirmed some results observed during previous epidemiological studies. In regards to symptoms present data suggest that biliary colic is the only specific symptom for gallstone disease. In addition, the high number of asymptomatic gallstones observed in this study suggests the need of more investigations on high-risk populations in order to make earlier diagnosis and eventually to prevent the disease. PMID- 2188170 TI - [The clinical, histological and ultrastructural findings in a case of acute steatosis of pregnancy with a severe cholestatic syndrome]. AB - A case of acute steatosis in pregnancy featuring unusually severe cholestasis is discussed with details of the successful outcome for mother and foetus. The correspondence between clinical picture, histological and ultrasound findings is reported together with a detailed review of the latest reports in the literature and what they reveal about the true incidence of the disease, the variability of the clinical picture, whether and when it is better for both mother and child to interrupt. PMID- 2188171 TI - Costing nursing care: a review. PMID- 2188172 TI - Can the study of spontaneous drawings indicate those children with chronic illness? AB - A controlled study of children's drawings as a means of detecting those with chronic disease, in the form of asthma, was carried out. The drawings produced by 48 children with chronic asthma and those of 52 controls were studied blindly and independently by three observers. One observer used a scoring method, the second used direct assessment, based on experience of children with chronic disease. The third observer based the assessment on knowledge and the use of drawings in clinical practice. The observer with a knowledge of drawings per se was clearly superior (p less than 0.001) in detecting those with asthma, while the other two observers' ability was no better than chance. PMID- 2188173 TI - Prevention of preeclampsia by low dose aspirin. PMID- 2188174 TI - Ceftriaxone prophylaxis in surgery. PMID- 2188175 TI - Reduction with tetracyclines of excessive collagen degradation in periodontal and other diseases. PMID- 2188176 TI - Development of epithelial gene therapy for treatment of oral and other diseases. PMID- 2188177 TI - New approaches for controlling dental plaque pathogenicity. PMID- 2188178 TI - Host defense and oral candidiasis. PMID- 2188179 TI - Iconodontalgia III. PMID- 2188180 TI - Malignant neoplasms arising in endometriosis. AB - Ten cases of malignant tumors arising in foci of gonadal and extragonadal endometriosis are reported and added to 195 previously reported cases from the English literature. The ovary was the primary site in 165 (78.7%) of the cases, whereas extragonadal sites represented 44 (21.3%). Endometrioid adenocarcinomas accounted for 69% of the lesions, clear-cell carcinomas 13.5%, sarcomas 11.6%, and rare cell types 6%. Extragonadal lesions were mostly endometrioid tumors (66%) and sarcomas (25%). Tumors arising in endometriosis were predominantly low grade and confined to the site of origin. Radiation therapy was often able to control completely tumors limited to the pelvis, but was not beneficial in metastatic disease. Only one patient had a response to chemotherapy. Fourteen patients received postoperative progestin therapy, with a 77% 5-year survival. Follow-up has been reported in 86 patients. The tumor was either confined to the ovary (57), confined to the extragonadal site of origin (11), or spread throughout the peritoneal cavity (18). With each of these situations, the 5-year survival was 65, 100, and 10%, respectively. Fourteen patients had malignant transformation in endometriosis associated with presumed estrogenic stimulation; most lesions (69%) were well differentiated and the 5-year survival was 82%. After surgical resection, we recommend that progestin therapy be included in the treatment of cancer arising in endometriosis. The actual frequency of malignancy arising in endometriosis may be higher than reported. PMID- 2188181 TI - Defining altered fetal growth by second-trimester sonography. AB - A method of predicting birth weight from a single ultrasound examination between 18-28 weeks' gestation was evaluated prospectively in 315 obstetric patients with singleton pregnancies. Estimated fetal weight at the time of the ultrasound examination was used to predict actual birth weight. At delivery, the percent difference between the projected and actual birth weights was then used to define whether an infant was small, appropriate, or large for gestational age. This method appeared to be accurate and showed identical relationships to the presence of abnormal fetal heart rate patterns in growth-retarded infants as did the traditional birth-weight-for-gestational-age method of defining intrauterine growth retardation. PMID- 2188182 TI - Prophylactic insulin in the management of gestational diabetes. AB - One hundred eight gestational diabetics were randomized to receive either diet alone or diet plus insulin (20 units NPH and 10 units regular) for glycemic control. Blood glucose levels were evaluated weekly in a high-risk clinic where medical and nutritional support and counseling were provided. Among 68 women successfully treated for a minimum of 6 weeks, the mean birth weight, macrosomia rate, and ponderal index were reduced significantly in the insulin-treated group. Insulin reduced birth weights significantly in women with a delivery weight of 200 lb or more (4060 +/- 342 versus 3397 +/- 640 g) and in those with a delivery weight less than 200 lb (3324 +/- 448 versus 3047 +/- 394 g). No patient with good glucose control and a maternal delivery weight under 200 lb had a newborn over 4000 g. Patients failing glycemic control were at greatest risk (30%) for fetal overgrowth whether initially receiving insulin or not. Maternal obesity or failure to achieve glycemic control should alert the clinician to a substantially increased risk of macrosomia. PMID- 2188183 TI - The transverse cerebellar diameter in estimating gestational age in the large for gestational age fetus. AB - The transverse cerebellar diameter was measured in 62 nondiabetic and 30 diabetic women with large for gestational age fetuses. Using reference curves from 675 women with normal gestations between 14-42 weeks, head circumference and abdominal circumference overestimated gestational age significantly in both study groups, whereas the transverse cerebellar diameter did not. PMID- 2188184 TI - Transvaginal sonographic detection of the pseudogestational sac associated with ectopic pregnancy. AB - Fifty-seven of 261 patients (21.8%) referred with a presumptive diagnosis of an ectopic gestation had an extrauterine pregnancy. Five of the 57 ectopic pregnancies (8.8%) had a pseudogestational sac on transvaginal sonography. In four of these five cases, a single beta-hCG level had been obtained and did not help in differentiating an ectopic gestation from an early intrauterine pregnancy. A thorough assessment of the adnexa and cul-de-sac should be performed if a patient suspected of having an ectopic pregnancy has an apparent intrauterine gestational sac without a normal yolk sac or without detectable fetal cardiac activity. PMID- 2188185 TI - Quantifiable polyhydramnios: diagnosis and management. AB - Little has been written regarding the ultrasonographic quantification of polyhydramnios or its subsequent management. Therefore, we designed this study to define polyhydramnios using the amniotic fluid index of greater than 2 SDs above the mean for late second- to third-trimester pregnancies, or 24 cm or greater. One hundred twelve nondiabetic women referred to Women's Hospital, Los Angeles County/University of Southern California Medical Center with the descriptive diagnosis of polyhydramnios made by experienced ultrasonographers were included in the study. There was poor correlation between these descriptions and fetal outcome. Twenty-six were qualitatively described as having severe, 29 as moderate, and 57 as mild polyhydramnios. Forty-nine of the 112 patients met our definition of significant polyhydramnios by having an amniotic fluid index of 24 cm or more. This particular definition allowed the inclusion of all fetuses with serious structural defects and/or death. Seven patients had an amniotic fluid index less than 24 cm, but with the traditional quantitative definition of one pocket of 8 cm or more; none of these patients had poor fetal outcome. These data appear to suggest that the use of descriptive definitions of polyhydramnios or a single fluid pocket of 8 cm or greater should be discarded in favor of using an amniotic fluid index of 24 cm or more. Once the diagnosis of polyhydramnios is made, the patient should have a detailed sonographic evaluation, be offered cytogenetic studies, and have antepartum surveillance. PMID- 2188186 TI - Medicare intermediaries shift bulk of paperwork processing to doctors. PMID- 2188187 TI - Antigenic expression of neuron-associated class III beta-tubulin isotype (h beta 4) and microtubule-associated protein 2 (MAP2) by the human retinoblastoma cell line WERI-Rb1. A comparative immunoblot and immunocytochemical study. AB - The antigenic expression of two neuron-associated microtubule proteins, class III beta-tubulin isotype (h beta 4) and microtubule-associated protein 2 (MAP2), was evaluated in a comparative immunoblot and immunocytochemical study of the human retinoblastoma cell line WERI-Rb1 maintained for up to 30 days in three different in vitro conditions. Western blots were performed on whole sodium dodecyl sulfate extracts of cells grown in floating suspensions, on Gelfoam matrices and on coverslips. Immunoperoxidase histochemistry was performed on matrix cultures. Immunoblotting demonstrated that h beta 4 and MAP2 were present under all culture conditions. By immunocytochemistry, staining of cytologically undifferentiated cells with anti-h beta 4 and anti-MAP2 monoclonal antibodies was found on Gelfoam matrix explants. In contrast, glial fibrillary acidic protein was not detected by either immunoblots or immunocytochemistry. These findings are in keeping with the solely neuroblastic nature of this line and provide no evidence for its divergent (i.e. neuronal and glial) differentiation capacity. PMID- 2188188 TI - Acidic fibroblast growth factor distribution in normal human eye and possible implications in ocular pathogenesis. AB - Using a rabbit anti-acidic fibroblast growth factor (anti-aFGF) antiserum, we tried to establish a precise mapping of aFGF localization in normal human ocular structures, from samples obtained by autopsies. Cell cultures of retinal pigment epithelium and ciliary pigment epithelium were also established and immunofluorescence studies were performed after 1 month. Corneal and conjunctival epithelia were strongly positive for anti-aFGF antibodies as well as the subcapsular epithelium of the lens. The cortical fibers were weakly reactive and the lens nucleus negative. A strong intracytoplasmic reactivity was observed in the pigmented and nonpigmented epithelial cells of ciliary processes and pars plana, both ex vivo and in vitro. Retina was brightly positive, mostly in the photoreceptor and plexiform layers. The possible involvement of aFGF in normal eye growth and in various ocular diseases was then discussed. PMID- 2188189 TI - Anisometropia and changes in anisometropia in school myopia. AB - Human anisometropia and changes in it were followed over a 3-year period in 238 schoolchildren who had uncomplicated school myopia in both eyes. Anisometropia of the spherical equivalent (ASFE) type increased in 27%, decreased in 6%, and remained unchanged in 67% of these children. When mean myopia increased from 1.43 to -3.06 D, mean ASFE increased from 0.30 to 0.51 D and the anisometropia of astigmatism (AAST) from 0.15 to 0.23 D. The faster the increase in myopia the greater was the increase in ASFE (r = 0.133, N = 238, p = 0.020). The higher the spherical equivalent at the end of the study the higher was the ASFE (r = 0.135, N = 238, p = 0.019). The initial refractive error or the amount or the axis of astigmatism did not have any prognostic value for the changes in ASFE. The higher the ASFE at the end of the study the higher also was the AAST (r = 0.136, N = 238, p = 0.018). The change in ASFE was independent of the wearing of spectacles. The distribution of the anisometropia of the spherical equivalent and its change followed a nearly normal distribution with the peak of eyes at about +/- 0 refraction. PMID- 2188190 TI - Homo quintadus, computers and ROOMS (repetitive ocular orthopedic motion stress). AB - Inherent conflict exists between computer systems and ocular physiology of Homo quintadus. Adverse ocular side effects of excessive saccades, excyclotorsion, supraduction, excessive field-of-fixation usage, capitas extension, astigmatic changes, otostatic reflex mismatching, and needless orthopedic malfunctions are imposed upon computer operators. Although the orthopedic dysfunctions are commonly grouped under the heading of Repetitive Strain Injuries (RSI), the inextricable linkage to poor ocular-neurological function argues for postulation of a broader schema entitled Repetitive Ocular Orthopedic Motion Stress (ROOMS). Concepts of good tool usage, total tactile familiarity, total proprioceptive familiarity, and visual cone-of-comfort clash with the installed-equipment base and indicate need for an integrated computer work station to facilitate near covisualization of screen/keyboard and to afford freedom-of-choice for optimal hand/eye synchronicity. The advocacy of computer operators' needs by user-welfare groups, universities, labor unions, and government agencies are portents for achieving genuine improvements. PMID- 2188191 TI - Pterygium in the tropics. PMID- 2188193 TI - Intraorbital wood. Detection by magnetic resonance imaging. AB - The authors present two cases in which intraorbital wooden foreign bodies remained undetected after initial ophthalmologic examination and radiologic investigation which included plain orbital x-rays, orbital computed tomography (CT) scans, and, in one case, orbital ultrasound. In each case, subsequent magnetic resonance imaging (MRI) showed a well-delineated low-intensity lesion suggestive of a retained foreign body. Investigation of a case of suspected wooden foreign body in the orbit should include an MRI scan if there is no contraindication, and no foreign body has been defined on CT scan, ultrasound, or plain orbital films. PMID- 2188192 TI - Contact transscleral continuous wave neodymium:YAG laser cyclophotocoagulation. AB - Advanced glaucoma in 140 eyes of 136 patients was treated with contact transscleral continuous wave neodymium:YAG (Nd:YAG) laser cyclophotocoagulation (CYC) with a sapphire-tipped probe. The anterior edge of the probe was placed 0.5 to 1.5 mm posterior to the limbus, using 7 to 9 W of power for 0.7 seconds with 32 to 40 applications, sparing the 3 and 9 o'clock meridians. Patients were studied prospectively. The mean preoperative intraocular pressure (IOP) of 36.7 +/- 0.97 mmHg decreased to 21.2 +/- 0.99 mmHg (P = 0.004) after treatment (mean follow-up, 3.2 +/- 0.35 months) for a mean decrease in IOP of 15.5 +/- 1.21 mmHg and a mean percent decrease of 39%. Forty-one eyes were followed 6 or more months (mean, 6.7 +/- 0.25 months). The CYC reduced IOP to 25 mmHg or less in 71% of eyes, to 22 mmHg or less in 62% of eyes, and to 19 mmHg or less in 49% of eyes. Maximum lowering of IOP occurred 1 week to 1 month after treatment and remained at that level through 6 months of follow-up. Retreatment was required in 11% of patients; only one patient was retreated more than once. Four patients treated with 9 W of power developed IOPs below 5 mmHg; two of these patients had an IOP of 0 mmHg. Other complications of therapy were minimal, and patients had little pain. There was no significant change in visual acuity. Early results of this newly available therapy are encouraging. PMID- 2188194 TI - Immunohistochemical evidence for IgE involvement in Graves' orbitopathy. AB - Orbital muscle and adipose tissues from seven Graves' orbitopathy patients were studied with in situ assays for IgE. The cases varied in disease severity and site biopsied. Two monoclonal and one polyclonal anti-IgE reagents produced similar results. Identically prepared monoclonal anti-IgM and anti-IgG antibodies and tissues obtained from five patients treated for unrelated orbital disorders were used as controls. Graves' tissues exhibited extravasated leukocytes and leukocyte-rich vessels. These leukocytes were mostly lymphoid. Some basophils and mast cells were identified and polymorphonuclear cells were abundant within vessels of adipose tissue. IgE-positive material was found in association with the majority of leukocytes and with muscle fibers. Parallel sections reacted with anti-IgM antibody were negative, whereas anti-IgG produced diffuse staining with no specific structures highlighted. Control, non-Graves' tissues had no evidence of immune cell activity and were either negative or displayed reactions with anti IgE reagents that were in most cases different from those of Graves' tissue. Serum IgE was measured in six of the seven patients and was elevated in the two patients with fulminating disease. PMID- 2188195 TI - Endogenous Candida endophthalmitis. Management without intravenous amphotericin B. AB - Eight consecutive cases of culture-proven endogenous Candida endophthalmitis (ECE) were managed between 1980 and 1988. All patients were treated with vitrectomy and injection of intravitreal amphotericin B. Blood cultures were negative in all patients, although Candida albicans was cultured from a foot ulcer in one patient. No systemic therapy was used in three patients, three patients received oral ketoconazole, and two patients received oral flucytosine postoperatively. Intravenous amphotericin B was not used because of lack of evidence of disseminated candidiasis and the systemic toxicity associated with its use. The ECE responded favorably to treatment in all cases. Final vision was better in patients with a shorter interval between onset of symptoms and initiation of antifungal therapy. Posttreatment visual acuities were: four eyes greater than or equal to 20/50, two eyes at 20/80 to 20/200, and two eyes less than 5/200. This series showed that ECE without evidence of disseminated disease can be treated successfully with vitrectomy and intravitreal amphotericin B. PMID- 2188196 TI - [The significance of HbA1 determination in children]. AB - The determination of glycated haemoglobin permits a good evaluation of metabolic regulation of diabetics. The development of vascular complications depends on duration and degree of hyperglycemia. It is presented the different chemical reactions of glucose with proteins in diabetes. The consequences are structural and functional changes of a variety of human proteins. This is a part of long term complications of diabetics. Collagen is used as an example for a protein with a relatively slow turnover rate that could allow for an accumulation of altered protein. PMID- 2188197 TI - Malignant tumors of the upper extremity in children. AB - Of the 422 primary malignant tumors of bone and soft tissue treated at one institution between 1968 and 1988, the 29 found in the upper extremity in children are reviewed. In the latter group, there were 13 patients with osteosarcoma; one was lost to follow-up shortly after diagnosis, one was alive and disease free four years after surgery, two are currently being followed, and nine are dead. All of the four patients with Ewing's sarcoma died. Three patients had chondrosarcoma; one was lost to follow-up after surgery, and the other two were disease free at four and 14 years' follow-up. Two of the nine patients with soft-tissue sarcomas died as a result of their tumors. PMID- 2188199 TI - Nutrition and pregnancy. PMID- 2188198 TI - Acute anterior thigh compartment syndrome complicating quadriceps hematoma. Two case reports and review of the literature. AB - Acute compartment syndrome of the thigh has been reported infrequently. To date, only eight cases from isolated blunt trauma without fracture have been reported. Two additional cases caused by intramuscular hematomas following blunt, low energy trauma, which were treated successfully with emergency fasciotomies, are presented. The morbidity from this syndrome varies from mild, with quadriceps weakness, fatigue, and myositis ossificans, to severe, with limb-threatening vascular compromise. Morbidity can be avoided if a high level of suspicion is maintained, compartment pressures are measured, fasciotomies are performed, and hematomas are drained. Postoperatively, patients can expect a dramatic decrease in pain and a quick return of quadriceps function with aggressive physical rehabilitation. PMID- 2188200 TI - Nutritional assessment for the primary care pediatrician. PMID- 2188201 TI - Organ-specific disposition of group B streptococci in piglets: evidence for a direct interaction with target cells in the pulmonary circulation. AB - Despite the serious pulmonary manifestations of early onset group B streptococcal (GBS) sepsis, it is not known whether the organism distributes into lung tissue and whether adverse pulmonary hemodynamic abnormalities relate to an interaction between the organism and target cells in the pulmonary vascular bed. Accordingly, this study evaluated the distribution and fate of GBS in the lung, liver, and spleen of anesthetized infant piglets and in isolated, salt solution-perfused piglet lung preparations. GBS were radiolabeled with 111Indium-oxine and infused at a dose of 10(8) organisms/kg/min for 15 min into anesthetized piglets ranging in age from 5-10 d. Forty-five min after termination of the infusion, animals were killed and specimens of lung, liver, spleen, and blood were excised and the relative deposition and viability of GBS were determined. Most of the recovered bacteria were detected in the lung (53.2 +/- 3.9%) followed by the liver (41.4 +/ 2.0%) and spleen (2.2 +/- 0.38%). GBS detected in the blood was estimated to be only 3.2 +/- 1.0% of the infused dose. Viability of GBS was least in the lung (21.4 +/- 2.6%) relative to the liver (45.7 +/- 11.2%) and spleen (83.4 +/- 19.5%). After a 60-min GBS infusion, transmission electron microscopy localized the organism within pulmonary intravascular macrophages in the lung; there was no evidence for bacterial interaction with either neutrophils or endothelial cells. In the liver, GBS was found exclusively in Kupffer cells. In isolated piglet lungs perfused at a constant flow rate with blood-free physiologic salt solution, GBS (10(6) to 10(8) organisms/mL) provoked concentration-dependent increases in pulmonary vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188202 TI - Metabolic and hematologic effects and immune complex formation related to pertussis immunization. AB - Selected metabolic, hematologic, and immunologic functions were evaluated in 3- to 6-mo-old Finnish infants who received whole-cell pertussis-component diphtheria and tetanus toxoids and pertussis vaccine, adsorbed (DTP) vaccine, and in 4- to 6-y-old Los Angeles children who received either a licensed DTP vaccine or an acellular pertussis component DTP vaccine. One d after immunization, there was an increase in total leukocytes and neutrophils and a decrease in lymphocytes in all vaccinees. In 4- to 6-y-old children the leukocytosis and neutrophilia were greater in recipients who received the standard DTP vaccine than in vaccinees who received an acellular pertussis component DTP vaccine. In infants there was an increase in the mean plasma insulin concentration but no change in the glucose concentration 24 h after immunization; no increase in the mean plasma insulin was noted in the 4- to 6-y-old children. Three 4- to 6-y-old vaccinees had higher circulating immune complex concentrations after immunization and two of these children had high clinical reaction scores. The etiology of adverse reactions after DTP immunization is multifactorial. In contrast with findings in animals, our findings do not demonstrate a clinically significant effect due to lymphocytosis-promoting factor on glucose metabolism in vaccinated children. Neutrophilia in vaccinees is probably due to endotoxin, and some reactions may be due to circulating immune complexes. PMID- 2188203 TI - Maternofetal transfer of IgG anti-Escherichia coli antibodies with enhanced avidity and opsonic activity in very premature neonates. AB - Total IgG concentrations, IgG antibody concentrations to pooled Escherichia coli antigens, and IgG anti-E. coli antibody avidity were measured in cord and maternal serum samples collected from 52 mother-infant pairs after premature delivery (mean gestational age 28 wk, range 23-33 wk). The mean IgG anti-E. coli antibody concentration in cord serum (1.86 relative units/mL) was markedly lower than in maternal serum (5.42 relative units/mL) at this gestation (p less than 0.0001). Cord serum IgG anti-E. coli antibody concentrations correlated closely with maternal IgG anti-E. coli concentrations when controlled for the effect of gestational age (partial correlation coefficient 0.89; p less than 0.001) but only weakly with gestational age when controlled for maternal IgG antibody concentrations (partial correlation coefficient 0.23; p = 0.06). The mean ratio of cord to maternal IgG anti-E. coli antibody concentrations was considerably lower than the mean ratio for total IgG concentrations (0.34 versus 0.72; p less than 0.001). The mean avidity of IgG antibody for the pooled E. coli antigens was significantly greater in cord serum than in maternal serum (2.45 versus 1.99M; p less than 0.0001). There was a close correlation between cord and maternal antibody avidity (r = 0.70; p less than 0.001), but cord IgG antibody avidity did not correlate with gestational age (r = -0.07; p = 0.61), nor with cord IgG anti E. coli antibody concentrations (r = 0.10; p = 0.50).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188204 TI - Blood flow velocity waveforms in the fetal cardiac outflow tract as a measure of fetal well-being in intrauterine growth retardation. AB - Maximum flow velocity waveforms were recorded in a longitudinal study from the fetal ascending aorta and fetal pulmonary artery in 46 normal pregnancies and, in addition, from the umbilical artery in 21 cases of intrauterine growth retardation between 19 and 33 wk gestation. In normal pregnancy, the mean peak systolic velocity (PSV) in the ascending aorta increased from 49.4 cm/s at 19 wk of gestation to 79.0 cm/s at 33 wk of gestation. The corresponding increase in PSV in the pulmonary artery was from 39.0 to 63.7 cm/s. The ratio for the PSV between the two arteries remained constant (1.25-1.29). Mean values of PSV in both arteries were linearly related to gestational age. Normal limits according to age were constructed by establishing the 5th and 95th percentiles. In intrauterine growth retardation, the PSV in the pulmonary artery was decreased (less than 5th percentile) in 95% of cases, PSV in the ascending aorta was reduced (less than 5th percentile) in only 57%. No relationship was established between PSV in both arteries and the presence or absence of end-diastolic flow velocities in the umbilical artery. The outcome of fetuses with intrauterine growth retardation, as expressed by Apgar score at 1 min and umbilical cord pH, bears no relationship to the PSV in ascending aorta and pulmonary artery. PMID- 2188205 TI - Source journals of articles on psychomotor performance: a list compiled from Index Medicus. AB - During 1988 in Cumulated Index Medicus under psychomotor skills, cross-referenced as psychomotor performance, 129 journals were listed. The three most frequently listed were Experimental Brain Research, Perceptual and Motor Skills, and Neuropsychologia. Questions important in evaluating journals, the information they provide on a topic, etc. are complex. PMID- 2188206 TI - The martial arts and mental health: the challenge of managing energy. AB - The effective management of energy is an important dimension in the martial arts as well as the mental health professions. The Oriental concept of Ki is described, noting its Indian, Chinese, and Japanese development. Ki and the transfer of energy is studied through the martial encounter, using concepts borrowed from Japanese swordsmanship. Ki is also discussed from a developmental context as youngsters progress in Tae Kwon Do training. In examining the disciplines of Aikido, Tae Kwon Do, and Karate, it becomes clear that more is involved than kicking, punching, and throwing bodies on the floor. These martial arts have some important statements to make in the area of mental health, particularly in terms of energy--within our bodies, psyches, interpersonal relationships, and the universe. PMID- 2188207 TI - "Faces and Feelings": a projective technique for measuring young children's self esteem. AB - A projective type "Faces and Feelings" measure was designed for use with kindergarten and first grade children. The underlying assumption was that the technique would elicit from this age group self-perceptions of worthwhileness. The unique methodology eliminated the most pervasive problems in self-esteem measurement, and results yielded important information about the effects of significant others on young children's self-esteem. Also, feelings about home and school activities addressed the multifaceted and specificity aspect of the self esteem construct. Differences between American and Australian children and boys and girls in how Mom, Dad, Teacher, Friend, Home, School, Holiday, Reading, Math made children feel about themselves could be identified using "Faces and Feelings." PMID- 2188208 TI - Death on the half-shell: the health hazards of eating shellfish. PMID- 2188209 TI - Norms of reaction: do they include molecular events? PMID- 2188210 TI - Enigmatic features of penile development and functions. PMID- 2188211 TI - Artificial ethology and computational neuroethology: a scientific discipline and its subset by sharpening and extending the definition of artificial intelligence. PMID- 2188212 TI - How to define life: a hierarchical approach. PMID- 2188213 TI - Bridging the aging-disease dichotomy. I. The amyloidosis model. PMID- 2188214 TI - Rudolf Virchow and the durability of cellular pathology. PMID- 2188215 TI - The French Revolution and the dilemma of medical training. PMID- 2188216 TI - From unpaid workers to respected scholars. PMID- 2188217 TI - Comprehensive discharge planning for hospitalized elderly: a pilot study. AB - The purpose of this randomized clinical trial was to examine the effects of a comprehensive discharge planning protocol implemented by a gerontological nurse specialist as compared to the hospital's general discharge planning procedure. There were no statistically significant differences between groups in length of initial patient hospitalization or in rates of posthospital infections. A statistically significant difference was found when groups were compared on the number of subjects rehospitalized during the study period. The findings of this pilot study reinforce the need for continued study of the impact of comprehensive discharge planning for hospitalized elderly. PMID- 2188218 TI - Who was Alice Fisher? PMID- 2188220 TI - Racism in nursing. Resource list. PMID- 2188219 TI - ITU for the mind. PMID- 2188221 TI - Nurse education. How to use ... gaming. Nurse Training Resource Group. PMID- 2188222 TI - Nurse education. Curriculum design. PMID- 2188223 TI - A cottage hospital at war. PMID- 2188224 TI - Using acupressure bands for postoperative nausea. PMID- 2188225 TI - Siblings of children with cancer. AB - The psychosocial concerns of siblings of children with cancer have been studied for more than 30 years. This article reviews the research and clinical literature on the major stressors affecting siblings of pediatric patients with cancer with particular focus on the coping process. The coping process includes adaptive and maladaptive coping strategies used by the children. Negative and positive sibling psychosocial responses to the diagnosis and treatment of a malignancy are detailed with suggested nursing interventions. PMID- 2188226 TI - Fundamentals for oncology nurse/data managers--preparing for a new role. AB - The nurse's role as a clinical trial data manager is a vital component of the success of the trial. Physicians rely on the nurse's expertise as a skilled observer to gather clinical data; act as a liaison to the many agencies involved in the study; instruct patients, families, and colleagues; and assess the information gathered. However, information about the nurse/data manager role is scarce. This article reviews information useful for the nurse assuming a clinical trial data manager position and for the nurse caring for patients on a research protocol. PMID- 2188227 TI - The epidemiology of ovarian cancer: a review. AB - Ovarian cancer is difficult to detect in an early stage when cure rates are higher. Because of this, it is important to identify women who may have a greater probability of developing the disease. The question of what factors influence a women's chances of developing ovarian cancer continues to be extremely difficult to answer. Nurses who understand the epidemiology of ovarian cancer and who are skilled in taking comprehensive health histories can play a major role in educating women to continue to obtain gynecologic screening exams, even in their postmenopausal years. PMID- 2188228 TI - An immunohistochemical localization of neuropeptide Y (NPY) in its amidated form in human frontal cortex. AB - The distribution of neuropeptide Y (NPY)-immunoreactive neurons was studied in human frontal cerebral cortex from surgical biopsy specimens by immunohistochemical techniques. NPY-containing neurons were identified in all cortical sublayers except sublayer I. The stained neurons were of the multipolar, bitufted, round or triangular form with dendritic and axonal processes. The immunoreactive neurons were considered to be cortical interneurons, due to their nonpyramidal form, and since their processes could be followed intracortically particularly in direction to superficial cortical layers. The NPY precursor molecule is processed to NPY by a dibasic cleavage, and NPY is further enzymatically amidated before release and receptor activation can be achieved. Antisera raised against Cys-NPY(32-36)amide recognize amidated NPY not cross reacting with nonamidated NPY. These antisera and immunohistochemistry revealed the presence of a population of NPYamide-immunoreactive cells morphologically indistinguishable from the NPY-immunoreactive cells in the human frontal cortex. By comparing the number of immunoreactive cells in adjacent sections, it appears that the number of NPY-immunoreactive cells was higher than those immunoreactive to NPYamide. Also, the density of NPY fibers was much higher compared with the number stained with NPYamide antiserum. The present immunohistochemical study indicates that NPY in its amidated form is contained in a subpopulation of human cortical NPY-immunoreactive neurons and may participate as an active neurotransmitter/modulator within the human cerebral cortex. PMID- 2188230 TI - Synthesis of bombyxin-IV, an insulin-like heterodimeric peptide from the silkworm, Bombyx mori. AB - Bombyxin-IV, a molecular species of bombyxin, which is a member of insulin-like heterodimeric peptides of the silkworm Bombyx mori with prothoracicotropic hormone activity, was synthesized. The A- and B-chains of bombyxin-IV containing four and two Cys residues, respectively, were first synthesized separately by solid phase chemistry using Boc protocol. Then they were coupled by stepwise removal of two different protecting groups at the cysteinyl thiols for semiselective formation of disulfide bridges to give bombyxin-IV in 8% yield. The synthetic bombyxin-IV was shown to have chromatographic and biological properties identical with those of natural bombyxin-IV. PMID- 2188229 TI - Amidated joining peptide in the human pituitary, gut, adrenal gland and bronchial carcinoids. Immunocytochemical and immunochemical evidence. AB - The distribution of the proopiomelanocortin-derivated amidated joining peptide (JP-N) was examined in the human pituitary gland, adrenal gland, gut and in three bronchial carcinoids. Double immunostaining showed coexistence of immunoreactive JP-N and other proopiomelanocortin derivatives, e.g., ACTH, beta-endorphin, Pro tau-MSH, in the pituitary gland and adrenal medulla. The JP-N immunoreactive cells in the adrenal medulla were identified as a subpopulation of adrenaline producing cells by means of an antiserum against phenylethanolamine N methyltransferase. In the gut immunoreactive JP-N was costored with somatostatin in endocrine cells. Using radioimmunoassay, JP-N was found in higher concentrations than ACTH and alpha-MSH in the gut but not in the adrenal gland. Gel chromatography of gastric antrum and adrenal gland extracts showed three and two dominating components of immunoreactive JP-N, respectively, but under reduced conditions most of the immunoreactive material appeared as of low molecular weight in both extracts. In conclusion, immunoreactive JP-N is a major product from the processing of proopiomelanocortin in human extrapituitary tissues. The molecular forms of immunoreactive JP-N correspond to previous findings in the human pituitary gland. PMID- 2188231 TI - Distribution of neuropeptide Y-like immunoreactive fibers in the cat thalamus. AB - Neuropeptide Y-like immunoreactivity was studied in the thalamus of the cat using an indirect immunoperoxidase method. The densest network of immunoreactive fibers was observed in the nucleus (n.) paraventricularis anterior. In the anterior, intralaminar and midline thalamic nuclei, as well as in the n. geniculatum medialis, n. geniculatum lateralis, n. habenularis lateralis, n. medialis dorsalis, n. lateralis posterior and n. pulvinar a low density of neuropeptide Y like immunoreactive fibers was observed. Neuropeptide Y-like fibers were totally absent in the n. ventralis lateralis, n. ventralis medialis, n. ventralis postero medialis and n. ventralis postero-lateralis. In addition, neuropeptide Y-like perikarya were found in the n. parafascicularis, n. suprageniculatus, n. geniculatum lateralis ventralis, n. medialis dorsalis and n. lateralis posterior. PMID- 2188232 TI - Metabolic clearance of insulin from the cerebrospinal fluid in the anesthetized rat. AB - Infusion of 125I-(Tyr A14)-insulin at tracer doses into the cerebrospinal fluid (CSF) resulted in a slow rate of increase in the CSF-labeled insulin during the first 2 hours with a plateau thereafter. Labeled insulin was cleared from the CSF at a higher rate than 3H-inulin, a marker of CSF bulk flow. The labeled insulin was mainly distributed in all the ventricular and periventricular brain regions. Small amounts of degraded insulin appeared in the CSF. Coinfusion with an excess of unlabeled insulin impaired the clearance and degradation of labeled insulin. It also inhibited the labeling in medial hypothalamus, olfactory bulbs and brain stem. In contrast, coinfusion of ribonuclease B (used to test the specificity of uptake) was without any effect. It was concluded that there is an active insulin intake from CSF into brain specific compartments that is presumably essential for the effects of insulin on brain function. PMID- 2188233 TI - The ostrich pituitary contains a major peptide homologous to mammalian chromogranin A(1-76). AB - A major peptide related to the NH2-terminal fragment (position 1 to 76) of mammalian chromogranin A was isolated from ostrich adenohypophyses following acid acetone extraction. The complete amino acid sequence of the homogenous peptide was deduced following automatic Edman degradation of the native peptide as well as of CNBr-, tryptic- and Lysobacter-derived peptides. The 76 amino acid sequence is strikingly homologous to bovine (80.3% sequence identity), porcine (79.0%), human (79.0%) and rat (72.4%) corresponding sequences, but much less so to human chromogranin B (22.4%). As this peptide is followed in bovine, porcine and human structure by a pair of basic residues (Lys-Lys), it could conceivably be produced during maturation in secretory granules. Finally, its structure appears to contain two potential amphipathic helices joined by the single disulfide bridge present in all chromogranin A and B molecules. PMID- 2188234 TI - Alteration and enhanced expression of the c-myc oncogene in human colorectal carcinomas. AB - We examined the alteration and expression of c-myc gene in 52 human colorectal carcinomas using Southern blot, Northern blot, Western blot and immunohistochemical techniques. Out of the 52 cases, only one case showed c-myc gene amplification of more than 4-fold. The overexpression of c-myc gene was detected in the tumor tissue of 47 cases (90.4%). In Western blot analysis, the c myc gene related proteins were detected in the tumor tissues which had the overexpression of c-myc gene. Immunohistochemically, c-myc p62 positive tumor cells were found in 24 cases (46.2%), while the stromal cells around the tumor cells showed c-myc p62 immunoreactivity in all cases (100%). The expression of c myc gene and c-myc P62 protein did not correlate with histological type, depth of tumor invasion and stage grouping. These findings indicate that the high incidence of the overexpression of c-myc mRNA in tumor tissues might account for the c-myc gene expression not only in tumor cells but also in stromal cells including lymphocytes, macrophages and fibroblasts. PMID- 2188235 TI - Bronchial carcinoids with S-100 positive sustentacular cells. A comparative study with gastrointestinal carcinoids, pheochromocytomas and paragangliomas. AB - Fourty-six bronchial carcinoids, twelve tumourlets and twenty areas of neuroendocrine cell dysplasia (NED) were immunohistochemically evaluated for various neuroendocrine markers, S-100 protein (S-100), myelin basic protein, intermediate filaments, actin, Leu-7 and several neurohormonal polypeptides. Eighteen of the bronchial carcinoids (39.1%) showed a biphasic cell pattern, with abundant stellate-shaped S-100 positive cells (SC). SC were not reactive for chromogranin A, myelin basic protein, cytokeratins, neurofilaments, glial fibrillary acidic protein or actin, and were only occasionally weakly positive for vimentin. SC were not detected in the tumourlets nor in the NED observed. For comparison a group of other neuroendocrine tumours (11 gastrointestinal carcinoids, 4 pheochromocytomas and 4 paragangliomas) were immunostained for S 100, chromogranin A and actin. SC similar to the ones detected in the bronchial carcinoids could be detected in appendiceal carcinoids, paragangliomas and in two out of four pheochromocytomas. Our present data are in keeping with a Schwannian/sustentacular nature of SC rather than that of a histiocytic or myoepithelial nature. We suggest that SC-rich bronchial carcinoids are biphasic tumours, which could be designed "paraganglioid" bronchial carcinoids. The relationship between SC-rich bronchial carcinoids and tumourlets/NED is a matter of further investigation: SC-rich bronchial carcinoids may either differentiate in a biphasic pattern during tumoural growth or may not be histogenetically related to tumourlets. PMID- 2188236 TI - What's new in the lymphocyte phenotype? AB - It is a relatively short period of time since the demonstration of surface immunoglobulin by immunofluorescence and the technique of cell surface rosetting first enabled in the identification of lymphocyte subsets. When we now examine the range of monoclonal antibodies which are available to lineage specific and lineage related epitopes the early methods used for the characterisation of normal or abnormal lymphocyte populations seem amazingly crude. The initial development by Kohler and Millstein of techniques for hybridising antibody producing cells to establish continuous lines and their development by large numbers of workers worldwide have provided a vast array of reagents available for cell phenotyping, ranging from the simplest diagnostic determinations to the sophisticated analysis of lymphocyte subsets in development. Indeed, so great is the array of monoclonal antibodies available that the nomenclature has been standardised at four international workshops. The basic aim of these workshops has been to establish a standardised system for the identification of the different monoclonal antibodies available for staining lymphocytes and also to officially allocate antibodies to these groups. A wide range of techniques are employed by the many groups who contribute to these workshops in order to achieve these results. Despite these basic aims, it is also clear that a considerable amount of functional and molecular biological information has come from these large group studies. At the Oxford Workshop, held in 1986, the number of identified "Clusters of Differentiation" (CD) reached the figure 45.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188237 TI - Reticular erythematous mucinosis syndrome: review of the world literature and report of the syndrome in a prepubertal child. AB - An 8-year-old boy with reticular erythematous mucinosis syndrome had erythematous plaques on his chest, face, and arms for three years. Sun exposure resulted in pruritus and increased lesions. Histologic examination revealed a perivascular mononuclear cell infiltrate with hematoxylin and eosin staining, positive staining material between the dermal collagen bundles with alcian blue (pH 2.5) staining, and granular basement membrane deposits of IgM with direct immunofluorescence staining. Results of all lupus erythematosus serologies and porphyrin studies were negative. Minimal erythema dose determinations to ultraviolet A and B were normal, and the lesions could not be induced with high doses of irradiation. Topical sunscreens, corticosteroid cream, and systemic beta carotene produced no therapeutic benefit. PMID- 2188238 TI - Cat-scratch disease: a review of the literature. AB - Cat-scratch disease (CSD) is a common cause of chronic lymphadenopathy (especially regional) that primarily affects children and adolescents. The clinical diagnosis of CSD is based on the presence of three of four criteria, which may include a positive CSD skin test. Usually a benign, self-limiting disease, CSD may sometimes have atypical manifestations and serious complications, particularly in immunocompromised hosts. Cat-scratch disease is now known to be caused by a small, gram-negative, pleomorphic bacterium. Antibiotics are dramatically effective against CSD in immunocompromised patients, but are not [corrected] of proven benefit in typical cases. Most patients recover with only symptomatic treatment. This article reviews the history of CSD research, clinical features of typical and atypical CSD, and current topics of interest in CSD research, especially in the areas of diagnosis and treatment. PMID- 2188240 TI - High-density lipoprotein cholesterol. Recommendations for routine testing and treatment. AB - Evidence from epidemiologic, lipid intervention, and coronary angiographic studies demonstrates the importance of high-density lipoprotein cholesterol (HDL C) in coronary artery disease (CAD) risk. Data from these studies strongly support the measurement of HDL-C in all patients screened for CAD. Patients with low levels should be treated using nonpharmacologic measures. High-risk patients deserve consideration for specific drug treatment. PMID- 2188239 TI - Comparison of crotamiton 10% cream (Eurax) and permethrin 5% cream (Elimite) for the treatment of scabies in children. AB - Permethrin 5% cream (Elimite) was approved as a treatment for scabies by the U.S. Food and Drug Administration in September 1989. In a double-blinded, randomized study, it was compared with crotamiton 10% cream (Eurax) for the treatment of scabies in children 2 months to 5 years of age. Two weeks after a single overnight treatment, 14 (30%) of 47 children were cured with permethrin 5% cream, in contrast to only 6 of 47 (13%) of subjects treated with Eurax. Four weeks after treatment the figures were 89% and 60% cured for the two agents, respectively. In 10 of the 19 patients whose treatment failed, the condition became worse after therapy. The difference in efficacy in favor of permethrin was significant (P = 0.002). That agent also demonstrated greater effectiveness in reducing pruritus and secondary bacterial infections. Elimite offers a safe, efficacious, and cosmetically elegant alternative to Eurax in the treatment of scabies in children. PMID- 2188241 TI - Women and coronary artery disease. Gender confers no immunity. AB - Although women are, in general, at less risk of coronary artery disease (CAD) than men, they have some unique risk factors, especially if they are postmenopausal or diabetic. Cigarette smoking carries increased hazards for women because it is often accompanied by oral contraceptive use, a combination that promotes thrombogenesis. Hypertension, hypercholesterolemia, hypertriglyceridemia, a high waist-hip ratio of body fat distribution, and certain psychosocial factors, while they pose risks for both men and women, have aspects that are unique to women. Clinicians need to identify the gender-related aspects of CAD and intervene aggressively to minimize the special risks to their women patients. PMID- 2188242 TI - The smokeless tobacco 'time bomb'. AB - All healthcare professionals need to become aware of the extent and seriousness of smokeless tobacco use. In this article, the authors briefly review the current status of smokeless tobacco and describe its usage patterns and practices, pharmacologic (addictive) aspects, and associated health problems. They also suggest ways that primary care physicians can discover or prevent smokeless tobacco use in their patients. PMID- 2188243 TI - Diagnosis of esophageal motility disorders. AB - Esophageal motility disorders are now known to be a heterogeneous group of conditions that commonly cause dysphagia and chest pain. Motor dysphagia is usually provoked by solids and liquids (in contrast to mechanical dysphagia, which is usually provoked by solids only). Chest pain with these disorders is nonspecific and can mimic angina pectoris. In many patients with diffuse esophageal spasm or nutcracker esophagus, pain appears to be caused by abnormal sensory function rather than contraction abnormalities. Barium esophagography and esophageal manometry are complementary studies in the evaluation of motility disorders. PMID- 2188244 TI - Robinow's syndrome: prenatal diagnosis. AB - The prenatal diagnosis of Robinow's syndrome was accomplished in our case by measuring the length of the long bones and the ulna/humerus ratio. Although the prenatal sonographic appearance did not show the typical 8-week fetal face, pathological findings confirmed this particular feature. In view of the strongly suggestive family history, the authors consider the possible mechanisms of genetic inheritance. PMID- 2188245 TI - 'Fruit' signs and neural tube defects. PMID- 2188246 TI - Sister chromatid exchanges in first-trimester chorionic villi after in vivo and in vitro exposure to diagnostic ultrasound. AB - A study was done to evaluate the effects of diagnostic ultrasound on sister chromatid exchange (SCE) in first-trimester chorionic villi under controlled technical conditions. Chromosome analysis was performed by the direct method using spontaneous mitoses from the cytotrophoblast layer, and SCE visualization was accomplished by a 72 h treatment with 5-bromodeoxyuridine (BrdU) at a concentration of 10 micrograms/ml. The slides were stained with acridine orange. Immediately before first-trimester chorionic villus sampling, a group of ten pregnant women was exposed to diagnostic ultrasound for 20 min (in vivo exposure). This group of patients was compared with a control group who were not exposed. A mean value of SCE/cell frequency of 4.2 +/- 0.2 was found in the exposed pregnancies, while a value of 3.7 +/- 0.2 was observed in the control group. After in vitro exposure of chorionic villi obtained from elective abortions, the frequency of SCE/cell did not differ significantly among samples with different exposures (1, 2, and 3 h) and controls. The positive control (mitomycin C) yielded a significant increase in SCE frequency. PMID- 2188247 TI - 'Late CVS' international registry compilation of data from 24 centres. AB - Data on 2058 late CVS cases, i.e., placental biopsies after 12 completed weeks of pregnancy, were collected from 24 centres. Two major groups of indications with or without ultrasound findings suspicious of fetal chromosomal abnormalities can be differentiated. In the first group, the rates of cytogenetic anomalies (21 per cent) and fetal losses (10 per cent) are high. The respective figures for the low risk group are 6 per cent for chromosome anomalies and 2 per cent for total fetal losses. To evaluate this rapidly spreading new method further, more data are required and will be collected by the CVS registry based in Philadelphia, U.S.A. PMID- 2188248 TI - Prenatal detection of non-cardiac rhabdomyosarcoma. AB - The most prevalent soft tissue tumour in children is rhabdomyosarcoma. These tumours may develop within or outside of muscle anywhere in the body and at any age. We report what is apparently the earliest case of non-cardiac rhabdomyosarcoma detected prenatally. PMID- 2188249 TI - Multicystic dysplastic kidney: natural history of prenatally detected cases. AB - To delineate the natural history of fetal multicystic dysplastic kidneys (MDKs), all cases that were prenatally detected in the Prenatal Diagnosis Center of the University of Virginia from September 1985 to 31 August 1988 were reviewed. All patients were followed through the Center with serial ultrasound evaluations at approximately 4-week intervals, and each liveborn infant was evaluated and followed by one of the authors (S.S.H.). Of the 14 cases detected, ten were detected in the second trimester, the earliest at 16.5 weeks' gestation. Of the nine fetuses with non-lethal disease, there were two cases in which the lesion remained unchanged during observation. Both had an initial diagnosis in the third trimester. In those cases diagnosed in the second trimester (7), all showed an initial increase in the size and number of cysts, followed by involutional changes either in utero (2) or in the neonatal period (3). Two infants had immediate surgical removal of the MDK, one because of respiratory compromise, and the other because of an uncertain diagnosis on renal scan. Abnormalities of the contralateral kidney were found in 7 of 14 fetuses. Five were lethal conditions. Associated non-renal abnormalities were common in bilateral MDK (80 per cent), but rare in unilateral MDK (11 per cent). PMID- 2188250 TI - Prenatal diagnosis of Conradi's syndrome. Case report. AB - A case is described of the diagnosis by ultrasound scanning during the second trimester of Conradi-Hunermann's syndrome (asymmetrical rhizomelic limb shortening or chondrodysplasia calcificans punctata). The prenatal diagnosis of limb shortening deformities is discussed. PMID- 2188251 TI - Prenatal diagnosis of intrapericardial teratoma. AB - A case of intrapericardial teratoma diagnosed by ultrasound before birth is described. Planning for delivery and immediate neonatal intensive management allowed successful cardiac surgery, full resection of the tumour and full recovery. PMID- 2188252 TI - A trophoblast specific antigen, recognized by monoclonal antibody MA21, locates a unique trophoblast cell population in the murine placenta. AB - Monoclonal antibody MA21 recognized a 44kDa plasma membrane protein on F9 teratocarcinoma cells, trophectoderm of mouse peri-implantation-stage blastocyst and ectoplacental cone cells of 5 day postcoitum implanted blastocyst (Vernon, Linnemeyer and Hamilton, 1989). We show here that this antigen is expressed by trophoblast cells of the maturing placenta. Immunohistochemical assays of early and mature placental tissue sections, indirect immunofluorescence labelling of placental cultures and blastocyst outgrowths in vitro, and immunoprecipitation of 35S-labelled NP-40 extracts of placental cultures indicate the presence of a plasma membrane-associated antigen with the same characteristics as MA21 antigen of peri-implantation embryos and F9 teratocarcinoma cells. In sections of placentae, antigen-positive cells are always situated in a thin layer between trophoblastic giant cells and maternal tissue. In cultures of postimplantation stage embryos, attached trophoblast cells express MA21 antigen initially, but following transformation to the giant cell state, antigen is no longer expressed. These results indicate the presence of a plasma membrane protein antigen associated with a distinct population of cells believed to be trophoblast. We believe that these cells are the foremost trophoblast cells opposing maternal decidua and that they may give rise to secondary trophoblastic giant cells. PMID- 2188253 TI - Immunoreactive trypsin(ogen) in the sera of children with recent-onset insulin dependent diabetes and matched controls. The Swedish Childhood Diabetes Group. AB - To evaluate the exocrine pancreatic function at the time of diagnosis of insulin dependent diabetes mellitus, we determined immunoreactive anodal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal trypsin(ogen) was 5 (quartile range, 3-7) micrograms/L in children with newly diagnosed diabetes, compared with a median level of 7 (quartile range, 4-8) micrograms/L in control subjects (p less than 0.0001). Similarly, the median level of cathodal trypsin(ogen) was 8 (quartile range, 4-10) micrograms/L in children with diabetes, compared with a median level of 11 (quartile range, 7-15) micrograms/L in control subjects (p less than 0.0001). The median of the individual ratios between cathodal and anodal trypsin(ogen) was 1.4 in the diabetic patients and 1.7 in the control children (p less than 0.001). In a multivariate test, however, only the decrease in cathodal trypsin(ogen) concentration was associated with diabetes. The levels of trypsin(ogen)s did not correlate with levels of islet cell antibodies, present in 81% of the diabetic children. Several mechanisms may explain our findings, for example, similar pathogenetic factors may affect both the endocrine and exocrine pancreas simultaneously, a failing local trophic stimulation by insulin on the exocrine cells may decrease the trypsinogen production, and there may be an increased elimination of trypsin(ogen) because of higher filtration through the kidneys in the hyperglycemic state. PMID- 2188254 TI - Proglumide analogues CR 1409 and CR 1392 inhibit cholecystokinin-stimulated insulin release more potently than exocrine secretion from the isolated perfused rat pancreas. AB - The effects of proglumide-related cholecystokinin (CCK) receptor antagonists CR 1409 and CR 1392 on CCK-octapeptide (CCK-8)-stimulated immunoreactive insulin (IRI) release and exocrine secretion were examined simultaneously in the isolated perfused rat pancreas. The CR 1409, at concentrations of 10-100 nM, significantly inhibited CCK-8 (100 pM) stimulation on IRI release but failed to inhibit the stimulatory effect of CCK-8 on both pancreatic juice flow and protein secretion. Increasing concentrations of CR 1409 inhibited both CCK-8-stimulated IRI release and exocrine secretion. Half-maximal inhibition was observed with approximately 2 nM for IRI release and 1 microM for protein secretion. When a higher dose (1 nM) of CCK-8 was used, the inhibitory effect of 10 nM CR 1409 on CCK-8-stimulated IRI release was abolished, whereas 10 microM CR 1409 retained significant inhibitory effect. Furthermore, 1 microM carbachol-induced IRI release was not altered by the addition of 10 microM CR 1409. The CR 1392 also had an inhibitory effect on both CCK-8-stimulated IRI release and exocrine secretion. The concentration of CR 1392 that caused half-maximal inhibition of CCK-8-stimulated IRI release was 300 times lower than that of exocrine secretion. In addition, 1 microM carbachol stimulated IRI release was not altered by 100 microM CR 1392. Thus, the inhibitory effects of CR 1409 and CR 1392 on IRI release were mediated through the interaction at the CCK receptor and were more potent than those on juice and protein secretion. This study suggests, therefore, that CCK receptors on B cells might be different from those on acinar cells in terms of their relative affinities for antagonists. PMID- 2188255 TI - Morphological findings in long-term pancreatic tissue transplants in the anterior eye chamber of rats. AB - Morphological changes in 21-day-old embryonic and 2-day-old postnatal rat pancreatic tissue fragments transplanted into the anterior eye chamber of homologous animals for 74, 77, 180, and 534 days were investigated using light and electron microscopic, acetylcholinesterase enzyme, and immunohistochemical methods. The pancreatic acinar cells degenerated and were not observed at this stage of transplantation. The ductal system proliferated and partly differentiated into endocrine cells that subsequently formed many new islets of Langerhans as well. The structures of beta-, alpha-, delta-, and pancreatic polypeptide cells were found to be intact even 1.5 years after transplantation. In addition to this, the organization of these cells inside the islets is similar to that of normal pancreatic tissue. The transplanted tissue fragments were well vascularized with blood vessels and innervated also by serotonergic cells and acetylcholinesterase-positive neurons. It is concluded that pancreatic tissue fragments, with the exception of the acinar component, can grow and survive with intact structure in the anterior eye chamber of homologous rats for up to 1.5 years. PMID- 2188256 TI - Effect of sulfhydryl reagents on pancreatic islet secretion granule-plasma membrane interaction. AB - To determine what role, if any, sulfhydryl groups may play in the fusion of islet secretion granules with the plasma membrane that takes place during exocytosis, we have studied the effect of several sulfhydryl-binding reagents, reducing agents, and oxidizing agents on the binding of 125I-labeled inside-out plasma membrane vesicles to isolated secretion granules. Three sulfhydryl-binding reagents, p-hydroxymercuribenzoate, Hg++, and N-ethyl maleimide, stimulated this binding, and the stimulation was greater in the absence of Ca++ than in its presence. In contrast, the three reducing agents used, glutathione, cysteine, and sodium bisulfite, inhibited the binding. Of the oxidizing agents, oxidized glutathione inhibited binding, whereas menadione and o-iodosobenzoate stimulated. The actions of Hg++ and glutathione were found to be on the secretion granules rather than the plasma membrane vesicles. It is concluded that the presence of a preponderance of sulfhydryl groups on the secretion granule membranes tends to limit their interaction with the plasma membrane and that these must be removed or masked for maximum fusion to occur. PMID- 2188257 TI - Seasonal changes in pancreatic insulin and glucagon in the little brown bat (Myotis lucifugus). AB - Seasonal changes in pancreatic insulin and glucagon were investigated in the little brown bat (Myotis lucifugus). Pancreatic protein content increased 21% from the nonhibernating state in June compared to the nonhibernating or early hibernating state in late October, and then decreased 50% between October and the months of deep hibernation. The content of insulin and glucagon increased from June to October, and both hormones further increased during hibernation, when a fall in pancreatic protein content occurred. The concentration of both insulin and glucagon increased from October to February. Of note, the insulin concentration progressively increased during deep hibernation from February to April, whereas the glucagon concentration remained constantly elevated throughout this time interval. The persistent elevation of pancreatic glucagon during hibernation may be related to its role in counterregulation and carbohydrate homeostasis during fasting. The elevation of pancreatic insulin, and its further increase during hibernation, is less clear but may be hypothesized to provide a rapidly releasable storage pool required for immediate secretion during arousal, possibly to prevent a hyperosmolar state. PMID- 2188259 TI - Endocrine pancreatic secretion in patients after acute pancreatitis. AB - In 14 nonobese patients after acute pancreatitis and with normal oral glucose tolerance, the response of insulin, C-peptide, and pancreatic glucagon after 100 g of oral glucose was assessed. The curves of insulin and C-peptide were significantly raised compared with those of controls, and no difference was found between the response of patients with a negative (n = 8) and a positive (n = 6) family history of type II diabetes. The curves of pancreatic glucagon did not differ from those found in controls. Our results indicate that a normal response to glucose after recovery from an attack of acute pancreatitis is maintained at the cost of increased insulin secretion. PMID- 2188258 TI - Juvenile idiopathic chronic calcifying pancreatitis: report of 10 cases from central Tunisia. AB - A series of 10 cases of chronic calcifying pancreatitis from central Tunisia are reported. The mean age at presentation was 23 years and the male to female ratio was 1.5. The main clinical manifestations of the disease were abdominal pain (eight cases), weight loss (four cases), and diarrhea (three cases). Diabetes was recorded in four cases. The etiological investigations yielded negative results in all the patients. It is concluded that central Tunisia should be added to the regions where juvenile chronic calcifying pancreatitis of the "tropical type" may be observed. PMID- 2188260 TI - De novo design of an alpha/beta barrel protein. PMID- 2188261 TI - An object-oriented database for protein structure analysis. AB - An object-oriented database system has been developed which is being used to store protein structure data. The database can be queried using the logic programming language Prolog or the query language Daplex. Queries retrieve information by navigating through a network of objects which represent the primary, secondary and tertiary structures of proteins. Routines written in both Prolog and Daplex can integrate complex calculations with the retrieval of data from the database, and can also be stored in the database for sharing among users. Thus object-oriented databases are better suited to prototyping applications and answering complex queries about protein structure than relational databases. This system has been used to find loops of varying length and anchor positions when modelling homologous protein structures. PMID- 2188263 TI - Synthesis, purification and initial structural characterization of octarellin, a de novo polypeptide modelled on the alpha/beta-barrel proteins. AB - We have attempted to construct an artificial polypeptide that folds like the eight-stranded parallel beta-barrel structures. Our approach consists of repeating eight times a unit peptide designed to adopt a 'beta-strand/alpha helix' pattern. A first 'test' sequence for this structural unit was deduced from a series of parameters defined after an analysis of three natural alpha/beta barrel proteins and including principally the lengths of the secondary structure elements, the alpha/beta packing and the fitting on average Garnier profiles. The gene encoding this structural unit was synthesized, cloned and expressed in Escherichia coli either as a monomer or as direct repeats of 2-12 units. Preliminary structural characterization of the 7-, 8- and 9-fold unit polypeptides by circular dichroism measurements indicates the presence of the predicted amount of alpha-helix in the three proteins. Further analysis by urea gradient gel electrophoresis demonstrates that, in the conditions tested, only the 8-fold unit polypeptide forms a compact structure through a cooperative and rapid two-state folding transition involving long-range molecular interactions. PMID- 2188262 TI - An 8-fold beta alpha barrel protein with redundant folding possibilities. AB - Protein sequences containing redundant segments of secondary structure at both termini have the choice a priori of folding into several possible circularly permuted variants of the wild-type tertiary structure. To test this hypothesis the gene of phosphoribosyl anthranilate isomerase from yeast, which is a single domain 8-fold beta alpha barrel protein, was modified to produce a 10-fold beta alpha homologue in Escherichia coli. It contained a duplicate of the two C terminal beta alpha units of supersecondary structure fused to its N-terminus. Most of the protein was recovered from the insoluble fraction of disrupted cells by dissolution in guanidinium chloride solutions and refolding. Pristine protein was purified from the soluble fraction. The purified (beta alpha)10 proteins were enzymically almost fully active. Absorbance, fluorescence and circular dichroism spectra as well as the reversible unfolding behaviour of both proteins were also very similar to the properties of the original (beta alpha)8 protein. Digestion with endopeptidases converted both the pristine and the refolded (beta alpha)10 variant to the same large fragment that had the N-terminal sequence and mol. wt of the wild-type (beta alpha)8 protein. The data suggest that the folding of the (beta alpha)10 variant is controlled thermodynamically both in vivo and in vitro. PMID- 2188264 TI - Construction of rat aldolase C expression plasmid and the hybrid formation between rat aldolase C and human aldolase A or B co-expressed in Escherichia coli. AB - Rat aldolase C cDNA was inserted in an Escherichia coli expression vector to construct the rat aldolase C expression plasmid, pRAC42. This plasmid produces active rat aldolase C in the transfected E. coli host cells. The characteristics of the purified enzyme, e.g. mol. wt, electrophoretic mobilities and kinetic parameters, are indistinguishable from those of authentic rat brain aldolase C. Three different tetrameric hybrid forms, C3A, C2A2 and CA3, in addition to C4 and A4, were found to be produced in the host cell when E.coli was co-transfected with expression plasmids for rat aldolase C and for human aldolase A. Similarly, the hybrid forms, C3B, C2B2 and CB3, in addition to C4 and B4, were also produced in the cells when co-transfected with the plasmids for rat aldolase C and for human aldolase B. PMID- 2188265 TI - Prostaglandins and the control of muscle protein synthesis and degradation. PMID- 2188266 TI - Ethologically-based animal models of anxiety disorders. AB - An overview of ethologically-based animal models suitable for investigating the pharmacological treatment of anxiety disorders is presented. The DSM-IIIR classification provides a framework for the discussion. The limitations of the models in current use are considered. It is suggested that there is a need for a greater emphasis on animal models of anxiety with an etiological basis. PMID- 2188267 TI - Phenytoin: pharmacogenetic polymorphism of 4'-hydroxylation. AB - The metabolism of phenytoin via 4'-hydroxylation is subject to large inter individual variability. The ratio of drug/metabolite (DPH/HPPH) in plasma and the reverse ratio for urine, metabolite/drug (HPPH/DPH), have been adopted to characterize the variability. Early recognition of the genetic/familial control of para(4'-)hydroxylation of phenytoin by Kutt and associates in the early 1960s was substantiated some 20 years later by Vasko et al. (1980) and Vermeij et al. (1988). The mode of inheritance has not been established. The frequency of 'insufficient' or slow hydroxylators is low, in the order of 1 in 500. The finding by Sloan et al. (1981) of an association between phenytoin 4' hydroxylation and the well known debrisoquine/sparteine polymorphism was not confirmed later by several other groups. Formation of the R-enantiomer of HPPH was clearly deficient in some Caucasian subjects and was linked to the mephenytoin polymorphism as shown by Fritz and associates (1987). PMID- 2188268 TI - Molecular genetics and the future of pharmacogenetics. AB - Recombinant DNA technology is a major innovation in medicine and is increasingly applied to study the mechanisms of inherited variations in drug response at the gene level. Three of these techniques are of particular importance to pharmacogenetics and for the study of the diversity of human genes. (1) Restriction analysis of genomic DNA, (2) enzymatic amplification of DNA by the polymerase chain reaction, and (3) the expression of cDNAs in cell culture. With these techniques large populations can be screened, normal and mutant DNA can be obtained from extremely small tissue samples, and functional expression of cDNAs allows the rapid search for potential new substrates of a polymorphic enzyme. PMID- 2188269 TI - The genetic polymorphism of debrisoquine/sparteine metabolism--clinical aspects. AB - It has been established that the metabolism of more than twenty drugs, including antiarrhythmics, beta-adrenoceptor antagonists, antidepressants, opiates and neuroleptics is catalyzed by cytochrome P-450dbl. The activity of this P-450 isozyme is under genetic rather than environmental control. This article discusses the therapeutic implications for each of the classes of drugs affected by this genetic polymorphism in drug metabolism. Not only are the problems associated with poor metabolizers who are unable to metabolize the compounds discussed, but it is also emphasized that it is difficult to attain therapeutic plasma concentrations for some drugs in high activity extensive metabolizers. PMID- 2188270 TI - The opioid system in neurologic and psychiatric disorders and in their experimental models. AB - Evidence from experimental and clinical studies suggests the involvement of the endogenous opioid system in several neurologic and psychiatric disorders (Alzheimer's, Huntington's and Parkinson's diseases, drug-induced movement disorders, Gilles de la Tourette syndrome, stroke, ischemia, brain and spinal cord injury, epilepsy, schizophrenia and affective disorders). However, its involvement is rather a secondary one, perhaps being a severe consequence of a primary, nonopioid disturbance. Thus, treatment of an opioidergic manifestation of a disorder of nonopioidergic origin is necessarily symptomatic and targets only the restoration of the opioid system; such treatment may be beneficial in ameliorating the clinical symptoms of the disorder. PMID- 2188271 TI - Peptides and vasomotor mechanisms. AB - The multiple and diverse roles played by neuropeptide Y, vasoactive intestinal polypeptide, substance P, calcitonin gene-related peptide and other biologically active peptides in the cardiovascular system are considered. A model of the vascular neuroeffector junction is described, which illustrates the interactions of peptidergic and nonpeptidergic transmitters that are possible at pre- and postjunctional sites. The effects of peptides on specific endothelial receptors are also described, which highlights the ability of these agents to act as dual regulators of vascular tone at both adventitial and intimal surfaces, following local release from nerves, or from endothelial cells themselves. Changes in expression of vascular neuropeptides that occur during development and aging in some disease situations and following nerve lesion are discussed. PMID- 2188273 TI - Photodynamic lipid peroxidation in biological systems. AB - Oxidative degradation of cell membrane lipids in the presence of molecular oxygen, a sensitizing agent and exciting light is termed photodynamic lipid peroxidation (photoperoxidation). Like other types of lipid peroxidation, photoperoxidation is detrimental to membrane structure and function, and could play a role in many of the toxic as well as therapeutic effects of photodynamic action. Recent advances in our understanding of photoperoxidation and its biomedical implications are reviewed in this article. Specific areas of interest include (a) reaction mechanisms; (b) methods of detection and quantitation; and (c) cellular defenses (enzymatic and non-enzymatic). PMID- 2188272 TI - Genetic and cellular basis of multistep carcinogenesis. AB - Experimental evidence indicates that cancer development is a multistep process, and that multiple genetic changes are required before a normal cell becomes fully neoplastic. These genetic changes involve oncogenes, tumor suppressor genes, and possibly senescence genes. From studies in vivo using several different animal models, the stages are broadly defined as initiation, progression, and clearly involve both genetic and epigenetic events. Studies in vitro using cell culture systems have allowed the multistep process to be dissected in greater detail at both the cellular and molecular genetic level. In the Syrian hamster embryo cell culture model, neoplastic progression requires four heritable changes, involving activation of two oncogenes and loss of two tumor suppressor genes. Like the experimental systems, a limited number of studies of human tumors suggest that the multistep paradigm is also applicable, and that similar genetic events are involved in the development of cancer in humans. PMID- 2188274 TI - [Occupational rehabilitation of psychiatric patients--a literature review for research and evaluation of occupational rehabilitation]. AB - After a short introduction to the topic of psychiatric evaluation research and the problems of vocational reintegration of psychiatric patients the article reviews the latest development in research on vocational integration. The analysis of literature scrutinizes the significance of different predictors concerning sociodemographic status, vocational aspects, status and treatment of mental illness and social relations. The various results are integrated and conclusions for the practice of vocational rehabilitation and further investigation are drawn. PMID- 2188275 TI - Cocaine produces locomotor stimulation in SS but not LS mice: relationship to dopaminergic function. AB - Cocaine produces several behavioral effects, most notably locomotor stimulation. While low doses of cocaine have been shown to decrease locomotor activity, moderate to high doses in the range of 5-50 mg/kg usually produce a marked increase in locomotor activity in rodents. This study examined the effects of a range of cocaine doses, 1-75 mg/kg, on locomotor activity in LS/Ibg (LS) and SS/Ibg (SS) mice. At the lowest doses, activity was depressed in both lines, but to a greater extent in LS mice. As the dose of cocaine was increased, activity returned to baseline, and at the highest doses, increases in locomotor activity were found, but only in SS mice. In LS mice, cocaine was ineffective in increasing locomotor activity at any of the doses tested. Since striatal dopaminergic neurons influence locomotor activity, we also assessed ligand affinity and receptor density of dopamine transporters and dopaminergic D1 and D2 receptors in striatal tissue obtained from these two selected lines. No differences in these receptor binding parameters were found. However, because of their anomalous locomotor response to cocaine, LS mice may prove to be a valuable tool in increasing our understanding of those sites which mediate specific effects of cocaine. PMID- 2188276 TI - Aniracetam tested in chronic psychosyndrome after long-term exposure to organic solvents. A randomized, double-blind, placebo-controlled cross-over study with neuropsychological tests. AB - In order to examine if the nootropic drug, aniracetam, was capable of improving cognitive performance, 44 subjects suffering from chronic psychosyndrome after long-term exposure to organic solvents were included in a randomized, double blind, placebo-controlled, cross-over study. The treatment periods were 3 months with aniracetam 1 g daily and 3 months with placebo. Neuropsychological tests as well as a physical and neurological examination were performed at entry into the study and after each treatment period, together with an evaluation of the subjects' overall condition. Neither the doctors' nor the subjects' own assessment of the overall condition indicated that the trial medication had had any effect. No significant changes in neuropsychological symptoms were observed. A statistically significant difference in favour of antiracetam was found in only 1 of the 19 neuropsychological test measures, namely a test for constructional ability. However, in another test on visuo-spatial function, a statistically significant result was found in favour of placebo. Thus, aniracetam was found to be ineffective in the treatment of subjects suffering from chronic psychosyndrome after long-term exposure to organic solvents. PMID- 2188278 TI - Biosynthetic incorporation of 15N and 13C for assignment and interpretation of nuclear magnetic resonance spectra of proteins. PMID- 2188277 TI - Behavioral effects of MK-801 in the rat. AB - Several experiments were conducted to study the effects of the noncompetitive N methyl-D-aspartate (NMDA) receptor antagonist, MK-801, on learning and memory in the rat. Rats displayed impaired performance on several sensorimotor tests and appeared grossly intoxicated when treated IP with 0.2 mg/kg MK-801, but not when treated with lower doses (0.05 or 0.1 mg/kg). Postacquisition performance on two spatial learning tasks involving working memory protocols (reinforced alternation and radial arm maze) was impaired by MK-801 at intoxicating doses (greater than or equal to 0.2 mg/kg) but not at lower doses (0.05 or 0.1 mg/kg). Using a position habit reversal task, we found that rats could learn to reverse a position habit while under the influence of a nonintoxicating dose of MK-801 (0.1 mg/kg), but when tested on the following day performed as if they did not recall what they had learned. Thus, acute administration of a nonintoxicating dose of MK 801 disrupts the retention of new information learned under the influence of the drug but does not interfere with the performance of tasks that are well learned before the drug is administered. Whether the performance deficits on the spatial learning tasks observed only following intoxicating doses of MK-801 reflect an effect on memory is not clear. PMID- 2188279 TI - Deuterium labelling in NMR structural analysis of larger proteins. PMID- 2188280 TI - Use of deuterium labelling in NMR studies of antibody combining site structure. PMID- 2188281 TI - Heteronuclear three-dimensional NMR spectroscopy of isotopically labelled biological macromolecules. PMID- 2188282 TI - [Radiogenic effects on liver tissue]. AB - In a review of literature the presented studies on radiogenic liver injuries are summarized. Whereas in the past the liver tissue was supposed to be radioresistant nearly completely, to newer knowledge this organ has to be classed with most radiosensitive tissues at all. The early picture of a liver injury in man is characterized by the veno-occlusive syndrome. Like in Budd-Chiari-Syndrome a congestion begins in the central veins and the centrolobular sinusoids, that has severest threatening consequences for the patients with extensive liver irradiation. The clinic picture is demonstrated. At present no suitable animal model exists for this disease yet. The presented pathological and electron microscopical findings do not allow any final estimation of the pathogenesis in this disease. The radiogenic late-effects are manifested in the liver in a centrolobular fibrosis, also starting from the Glisson's triangles, with cirrhotic reconstruction of liver architecture. The great compensatory power of the organ does not cause clinical pictures to be effected in radiotherapeutic practice with only partial liver irradiation in most cases. The dose-time relation of the radiogenic hepatitis shows a very little alpha-/beta-value. With this the liver renders as typical late-effect tissue and should be spared effectively by choice of small single doses. PMID- 2188283 TI - [The modifying effect of a hypoxic gas mixture on the development of radiation induced sclerosis]. AB - Female mice (CBA X C57 Bl) F1 were exposed a single total-body gamma-irradiation with a dose efficiency of 6.5 Gy/min with doses of 2.5-7.5 Gy in air or inhaling a gas mixture of 6-6.5% oxygen and 94-93% nitrogen. All naturally died animals were examined pathoanatomically. By means of the rate of cardio- and nephroscleroses a protective effect of hypoxia was found with a dose modification factor of 1.5. Dynamics and degree of intensity of a radiogenic pneumosclerosis were studied by means of a stereologic analysis 3, 6, and 12 months after a single roentgen irradiation of the right thorax half of rats with a dose efficiency of 2.2 Gy/min with doses of 10, 14.3, 20 Gy in air and 14.3 and 20 Gy inhaling a gas mixture with 10% oxygen and 90% nitrogen. Applying the criterion of accumulation of connective tissue within the irradiated lung the protecting effect of hypoxia was estimated according to the dose modification coefficient, that varied in a range of 1.0-1.64. PMID- 2188284 TI - [Significance of computed tomography in ophthalmologic diagnosis. II. CT of eyeball tumors, orbital tumors, nontumor space-occupying orbital processes and malformations]. AB - CT is valuable to complete ultrasound findings in the evaluation of tumors of the eyeball. Tumoral and nontumoral space-occupying lesions and malformations of the orbit and the exact demarcation of these conditions within the periorbital structures are well demonstrated. In several different pathological conditions the CT appearances are often similar and only sometimes characteristic. Additional clinical data are helpful in giving hints for the diagnostic differentiation of the CT findings. PMID- 2188285 TI - About the use of the Kitecko ultrasound stand-off pad. PMID- 2188286 TI - [The validity of selected nuclear medicine imaging procedures (brain, skeletal, and hepatobiliary diagnosis)]. AB - In a retrospective study we tested several scintigraphic investigations for a total of 2,014 patients. As reference we used the results of biopsy, autopsy or the epicritic final diagnosis before emission, summing all clinical signs as well as the results of additional alternative methods and other imaging methods. Criteria of validity (sensitivity, specificity, diagnostic accuracy) are used in a consistent manner. Brain perfusion scintigraphy detected acute cerebral perfusion disorder with a sensitivity of 0.87, differentiating for reversible and irreversible lesions. Carotid angiography had the same diagnostic validity. Because there is no loss of brain substance, the validity of CT and static brain scintigraphy was lower. Skeletal scintigraphy was highly sensitive for the detection of primary and secondary bone tumours as well as for the detection of inflammations and occult fracture. RHS-scintigraphy of the liver, presently used for tumour and metastasis diagnostics after sonography and CT, had a sensitivity of 0.79. It was more sensitive for detecting inflammatory RHS-liver disease (sensitivity 0.95). Biliary scintigraphy was seen under the surgical aspect only for selected questions. It was sensitive for the detection of biliary cyst disorder and the elucidation of complaints after biliary tract sanitation (sensitivities 0.92 and 0.84) and for the detection of duodenogastric reflux (0.7), but was of limited diagnostic value for the differentiation of hepatocellular and obturation icterus with a sensitivity of 0.5. PMID- 2188287 TI - [Determination of the radiation imparted to patients in x-ray diagnosis--methods and results]. AB - The amount of radiation committed to the patient is best described by appropriate organ doses. Methods for determining such dose values are described. For x-ray investigations of the chest, thoracic and lumbar spine, pelvis and kidney (excretion urography) our own organ-dose values are compared with those from the literature. PMID- 2188288 TI - [Bronchial carcinoma. Nuclear medical diagnosis]. AB - The primary indication for scintigraphy in the patient with bronchogenic carcinoma occurs during therapy planning, when scintigrams are obtained to prognosticate post-operative lung function. Ventilation and perfusion scintigrams are the procedures of choice for regional evaluation of lung function. Numerous radioisotope procedures have been introduced for recognition and evaluation of bronchogenic malignancies. In spite of the array of interesting diagnostic approaches, nuclear medicine has failed to reach a prominent position in the diagnostic evaluation of these malignancies. The limits and special indications for using scintigraphic procedures are discussed. PMID- 2188289 TI - [Differential breast diagnosis using CW-Doppler ultrasound]. AB - There is no method that allows satisfactory differentiation between benign and malignant breast lesions. We were able to differentiate 94% of palpable malignant tumours with CW-doppler ultrasound, which helps to increase the efficiency of clinical examinations, breast sonography and mammography. Two hundred patients were examined with an 8 MHz CW-doppler probe. The symmetry of arterial vessels and flow velocity in normal breasts is very high. Carcinomas appear as areas with localized flow increase. Only in two normal patients was a minimal focus of two arteries found. PMID- 2188290 TI - [Clarification of an abdominal space-occupying lesion]. PMID- 2188291 TI - Diamond Jubilee lecture. Neuroradiology: past, present, future. PMID- 2188292 TI - A surgeon looks at cervical lymph nodes. AB - Squamous cell carcinoma is the most commonly encountered malignant neoplasm of the upper aerodigestive tract. The most important factor that influences therapeutic outcome is the development of metastasis to the cervical lymph nodes. Traditionally, assessment and staging have been based on clinical evaluation. Studies of clinicopathologic correlation have demonstrated that both the sensitivity and the specificity of the clinical examination findings are unsatisfactorily low in that false-negative rates may be 15%-25% while false positive rates may be similarly high. The clinician is caught in the position of having to overtreat many patients to avoid undertreating a few. The rapid advances in imaging technology introduced in the past decade have greatly affected our ability to identify cervical metastatic disease. With improved technology and increased experience, patients can be better characterized individually according to the status of the cervical lymph nodes so that therapeutic intervention can be appropriately designed. PMID- 2188293 TI - Symptomatic lower extremity deep venous thrombosis: accuracy, limitations, and role of color duplex flow imaging in diagnosis. AB - Color duplex flow imaging (CDFI) permits pain- and risk-free direct imaging of the deep venous system of the lower extremities. To prospectively ascertain the accuracy and limitations of this technique, CDFI was performed in 75 lower limbs of 69 consecutive patients referred for venographic evaluation of clinically suspected lower extremity deep venous thrombosis (DVT). The CDFI study was obtained within 24 hours of the contrast venogram. Both studies were interpreted without knowledge of the patient's clinical findings or the results of the other test. Contrast venography was regarded as the standard for diagnosis of DVT. Accuracy was 99% for detection of DVT above the knee and 81% below the knee. Sonographic evaluation of the calf veins was technically adequate in 60% of limbs; accuracy was 98% in this group. In the 40% of limbs with technically limited CDFI studies of the calf, accuracy decreased to 57%. Although small nonocclusive thrombi occurred infrequently in this series of symptomatic patients, CDFI missed three of four such thrombi. It is concluded that CDFI, when not technically compromised, is sufficiently accurate to definitively diagnose symptomatic lower extremity DVT. PMID- 2188294 TI - Outcome analysis of patients with normal compression US examinations. AB - Prior studies have documented the accuracy of compression ultrasound (US) for use in evaluating patients with clinically suspected deep venous thrombosis (DVT) of the lower extremity. A normal compression US examination is considered indicative of no thrombotic disease, and anticoagulant therapy is withheld. There are no long-term data supporting treatment decisions based solely on normal compression US results. The authors undertook a long-term (8-33-month) review of 1,111 normal compression US examinations performed on 1,022 patients. Outcome analysis obtained through review of imaging records, inpatient charts, and death certificates failed to document sequelae of untreated DVT in all but five patients with negative examinations. Three patients again presented with clinical symptoms of DVT that were subsequently documented with compression US, and two patients reportedly died of pulmonary embolism with no documentation of DVT several months after the initial negative study. Because of the clinical acceptance of this test and the subsequent increased demand for its use, compression US has quadrupled the yearly detection rate of DVT at the authors' institution. With the results of prior controlled studies and this favorable outcome analysis study, compression US is recommended as the diagnostic modality of choice for suspected DVT. PMID- 2188295 TI - Axillary and subclavian venous thrombosis: follow-up evaluation with color Doppler flow US and venography. AB - Real-time ultrasonography (US) and color Doppler flow mapping were used to determine prospectively whether venous thrombosis in the upper extremity could be imaged as accurately as with conventional contrast venography. Thirteen patients were imaged. The diagnosis of spontaneous (or "effort") thrombosis was made clinically and confirmed initially at venography (n = 11) or at technetium-99m dynamic scintigraphy (n = 2). After therapy, follow-up imaging with color Doppler flow US and venography was performed in all 13 patients for correlation. Absence of flow signals was noted in five patients with complete occlusion of the subclavian vein, and decreased flow signal was seen in two patients with partial obstruction of the subclavian vein. In five patients, findings returned to normal at color Doppler flow US and venography, and patent collateral veins were seen in one patient. The authors conclude that color Doppler flow US is useful in evaluating venous thrombosis in the upper extremity and might be preferable to venography for follow-up because the discomfort of injection and risk of contrast material-induced phlebitis are eliminated. PMID- 2188296 TI - Extracorporeal shock wave lithotripsy of calcified gallstones. Work in progress. AB - Thirty-eight patients with calcific cholecystolithiasis underwent extracorporeal shock wave lithotripsy (ESWL) of the gallbladder on an outpatient basis. Twenty two (60%) patients had fragments smaller than 3 mm on follow-up ultrasound (US) studies after an average of 13,450 shock waves and four lithotripsy sessions. Nineteen of these 22 patients were followed up for an average of 18 weeks, and only three were found to be free of residual fragments at US. The other three patients were lost to follow-up. Sixteen patients are still undergoing biliary ESWL. Comparison of calcified and noncalcified gallbladder calculi revealed that calcified stones required 50% more shock waves for successful fragmentation, fragments cleared considerably more slowly from the gallbladder, and patients had a higher frequency of acute pancreatitis (5% vs 2%) and transient hematuria (8% vs 3%). Stones with dense homogeneous calcification required significantly fewer shock waves for successful fragmentation than stones with calcific lamination. ESWL can be applied occasionally in patients with calcific cholecystolithiasis if an alternative to surgery is required, but success has been limited. PMID- 2188297 TI - Hemostatic protein-polymer sheath: new method to enhance hemostasis at percutaneous biopsy. AB - Serious hemorrhagic complications have been reported with percutaneous biopsy, albeit infrequently. A hemostatic protein-polymer sheath (PPS) designed to limit the risk of bleeding was evaluated by performing liver biopsies on pigs given anticoagulants. After administration of anesthesia and laparotomy, biopsies were performed under direct vision with a cutting biopsy needle (a) alone, (b) fitted with the PPS, or (c) fitted with a thrombin-coated PPS. Dry sponges were applied and subsequently weighted to quantitate blood loss. At all levels of anticoagulation, use of the PPS enhanced hemostasis; the thrombin coating supplemented effectiveness. The PPS appears to be a simple and effective method of achieving hemostasis at high-risk percutaneous biopsy. PMID- 2188298 TI - Fetal choroid plexus cysts: a report of 100 cases. AB - A prospective study was undertaken to evaluate the prevalence and significance of fetal choroid plexus cysts detected on screening ultrasound (US) scans. One hundred cases of fetal choroid plexus cysts were detected from 11,700 examinations: There were 95 healthy newborns, three newborns with trisomy 18, one newborn with syndactyly of the toes, and one intrauterine death. In the three neonates with trisomy 18 the cysts were large (greater than 1 cm in diameter), and additional abnormalities were detected. Although there is a clear association between fetal choroid plexus cysts and trisomy 18, amniocentesis or chorionic villus sampling should be reserved for high-risk patients with either large cysts or US evidence of other abnormalities. PMID- 2188299 TI - Right common carotid artery ligation for extracorporeal membrane oxygenation: cerebral blood flow velocity measurement with Doppler duplex US. AB - Duplex Doppler ultrasound (US) provides a noninvasive method of monitoring cerebral blood flow velocity in newborns. The authors observed the changes in cerebral blood flow velocity in the right middle cerebral artery (RMCA) in 15 neonates during right common carotid artery (RCCA) ligation for extracorporeal membrane oxygenation. Antegrade flow in the RMCA continued uninterrupted in all patients at the moment of ligation. Peak systolic velocity decreased initially and then increased to 70% of baseline levels in the following 3-5 minutes. End diastolic velocity remained relatively unchanged at the time of ligation and rose slightly above baseline during the following 3-5 minutes. This study demonstrates that at the time of RCCA ligation, collateral flow is immediately established in the RMCA distribution and is further augmented within minutes. PMID- 2188300 TI - Response of osteosarcoma and Ewing sarcoma to preoperative chemotherapy: assessment with dynamic and static MR imaging and skeletal scintigraphy. AB - In 15 osteosarcomas and six Ewing sarcomas, response to preoperative chemotherapy was assessed with magnetic resonance (MR) imaging without and with gadolinium diethylenetriaminepentaacetic acid (DTPA) enhancement and with dynamic Gd-DTPA studies, and the results were compared with the scintigraphic findings. All studies were obtained prior to and following preoperative chemotherapy. Static MR imaging was of little value for assessment of response; reduction in signal intensity within soft-tissue masses on the T2-weighted spin-echo images indicated response with a sufficient degree of accuracy (71%) but low sensitivity, whereas an increase in signal intensity after Gd-DTPA administration indicated zones of viable tissue with low specificity. With three-phase skeletal scintigraphy, the findings in the perfusion and blood-pool phases were of no value, whereas the findings in the osseous phase allowed the prediction of response with an accuracy of 73.7%. Of all techniques employed, dynamic MR imaging had the highest degree of accuracy (85.7%) and was superior to scintigraphy, particularly in patients who were receiving intraarterial chemotherapy. PMID- 2188301 TI - Suspected testicular torsion and ischemia: evaluation with color Doppler sonography. AB - Color Doppler sonography was performed in 32 patients with a painful scrotum in whom testicular ischemia from torsion or postherniorrhaphy was clinically suspected. Surgical correlation was available in 15 patients, and scintigraphic correlation was available in 17 patients. Seven of the 32 patients were diagnosed as having testicular ischemia from torsion. Color Doppler flow imaging demonstrated a lack of intratesticular flow in six of the seven testes with torsion and relatively normal intratesticular flow in one of the patients with acute torsion. Normal or increased intratesticular flow was demonstrated by color Doppler in all 57 of the nonischemic testes. Using the single criterion of presence or absence of identifiable intratesticular flow, the authors found that color Doppler was 86% sensitive, 100% specific, and 97% accurate in the diagnosis of torsion and ischemia in the painful scrotum. Color Doppler sonography is an accurate, noninvasive means of rapidly assessing perfusion of the testis in the painful scrotum. PMID- 2188302 TI - Treatment of autonomous thyroid nodules with percutaneous ethanol injection: preliminary results. Work in progress. AB - Eight patients with autonomous thyroid nodules 2.4-4.3 cm in diameter received percutaneous ethanol injections (PEIs) under guidance by means of ultrasound (US). Sterile ethanol at 95% was injected with a 22-gauge needle and a 7.5-MHz probe with a guide device. Each patient received one or two treatments, with 1-3 mL of alcohol (depending on the nodule size) per treatment, each week for a total of three to six injections per lesion. After a total of 36 injections in all eight patients, there were no complications. Follow-up ranged from 2 to 10 months. After therapy, symptoms subsided and hormonal levels became normal or reached the range of subclinical hypothyroidism. Scintigrams showed that the previously suppressed thyroid tissue had resumed functioning. At US, all nodules had shrunk. PEI was risk free and easy to perform. If these preliminary results are confirmed in a larger study with longer follow-up, the new treatment may become an alternative to surgical or radioiodine ablation of autonomous thyroid nodules. PMID- 2188303 TI - Medicaid maternal and child health care: prepaid plans vs. private fee-for service. AB - A randomly selected sample of 98 inner-city new mothers was interviewed with regard to (a) their level of satisfaction with and perceived barriers to pediatric and maternal health care, and (b) the health status of their infants. The mothers were divided according to their Medicaid status: 39 (40%) were enrolled into a Medicaid prepaid plan (PPP) and 59 (60%) were enrolled as regular Medicaid fee-for-service (FFS) patients. Comparison of the two groups showed that infant health status was similar but that PPP mothers reported a higher incidence of untreated infant problems and perceived more barriers to pediatric care. Birth outcomes also were similar for the two groups but FFS mothers and infants were hospitalized for significantly longer periods postpartum. The implications of these findings for the delivery of maternal and child health services to low income populations through the Medicaid program are discussed. PMID- 2188304 TI - The relationship between task complexity and decision-making consistency. AB - The purpose of this study was to examine the relationship between task complexity and decision-making consistency using a normative decision model. The Decision Analytic Questionnaire (DAQ), an instrument designed to measure nurses' decision making under increasingly uncertain and complex conditions, was administered to a stratified random sample of 101 paid volunteer medical-surgical nurses drawn from three public teaching hospitals. Probit analysis was used to construct a profile of the decision maker whose decisions coincided with those of the model. Results indicated that nurses made clinical decisions that coincided with those recommended by a normative decision model but that agreement diminished as task complexity increased (p less than .005). The results also indicated that consistency was task specific, that predictive variables were a function of decision task and that more predictor variables were needed to explain consistency as task complexity increased. PMID- 2188305 TI - Color Doppler imaging of the iliofemoral region. AB - Color Doppler imaging has been used to evaluate a variety of abnormalities in the iliofemoral region. This pictorial essay demonstrates how use of color Doppler techniques aids in the diagnoses of iliofemoral pseudoaneurysms, fluid collections, aneurysms, arteriovenous fistulas and malformations, venous thrombosis, vascular grafts, and soft-tissue masses including tumors and benign lymphadenopathy. PMID- 2188306 TI - CT features of thoracic mycobacterial disease. AB - The authors review the computed tomographic (CT) features of thoracic tuberculosis and other mycobacterial infections throughout their progressive stages. The spectrum of parenchymal findings seen in mycobacterial disease as well as the chronic changes of prior tuberculosis are illustrated. Altered appearances of tuberculosis occurring in patients with preexisting chest diseases such as sarcoidosis and silicosis and those associated with acquired immunodeficiency syndrome are demonstrated. CT and conventional radiography are compared, and the advantages and complementary nature of CT are illustrated. The role of CT in evaluating complications of tuberculosis, including cavities, bronchogenic spread, bronchiectasis, and aspergilloma, is discussed. PMID- 2188307 TI - CT of malignant anal canal tumors. AB - Radiation therapy of malignant neoplasms of the anal canal has promising results in the majority of patients if the disease is limited at initial diagnosis. Computed tomography (CT), especially when performed with contrast material injected intravenously, is valuable in the pre- and posttreatment assessment of the anorectal musculature and perirectal nodes. The authors review the anatomy of the anorectal area and their experience with CT evaluation of anal canal cancer in a series of 26 patients. They also discuss their experience with treatment of this cancer in a series of 48 patients. PMID- 2188308 TI - Radiologic evaluation of continent urinary reservoirs. AB - A variety of methods are currently used for urinary diversion after cystectomy in adults. Radiologists are generally familiar with ileal and colonic conduits but are less familiar with the recently popularized continent urinary reservoirs. We describe and illustrate the surgical technique, normal anatomy, and normal radiographic appearance of a variety of urinary reservoirs, including the Kock pouch, Camey procedure, and various ileocecal reservoirs. Complications of various reservoirs are also discussed and illustrated. PMID- 2188309 TI - Evaluation of the lacrimal apparatus with digital subtraction macrodacryocystography. AB - Patients who suffer from epiphora can benefit from reconstructive surgery in many cases of obstructive and nonobstructive lesions of the lacrimal apparatus. We describe our technique of digital subtraction macrodacryocystography (DSM) and discuss its efficacy in the evaluation of various abnormalities involving the lacrimal drainage pathway. A variety of pathologic conditions of the lacrimal apparatus are portrayed. DSM is an accurate, easy to perform, but relatively unrecognized method of anatomic localization of obstructive lesions within the lacrimal drainage system. PMID- 2188310 TI - Case of the day. Ultrasound. Hepatic lipoma. PMID- 2188311 TI - Fibrous dysplasia. AB - Skeletal fibrous dysplasia is a developmental anomaly in which normal bone marrow is replaced by fibroosseous tissue. This process may be localized to a single bone, or even a small segment thereof, or affect the skeleton diffusely. The radiologic archives of the Armed Forces Institute of Pathology (AFIP) contain 501 cases of histologically proved and radiographically correlated fibrous dysplasia (of which 427 cases are monostotic and 74 cases are polyostotic). We present the spectrum of radiologic findings, including those from bone scintigraphy, computed tomography, and magnetic resonance imaging, augmented where appropriate by accompanying pathologic material. PMID- 2188312 TI - Costs and acceptability of two special overlays for the prevention of pressure sores. AB - In a randomized clinical trial, 187 adult patients with chronic neurologic conditions who were at a high risk of developing pressure sores were assigned for 3 months to either an alternating air (AA) mattress overlay or a silicore (S) mattress overlay. Costs associated with each overlay were calculated and compared by adding depreciation and yearly expenses related to maintenance, operation, and repair for 148 patients who completed the trial. Acceptability was measured by questionnaires and interviews involving 45 of the patients' primary nurses and a sample of 40 patients (20 from each overlay group). The annual cost of the AA overlay was 54% more than that of the S overlay. Although most nurses (more than 74%) believed that both overlays helped prevent pressure sores and deter their progression, many (more than 56%) would not recommend either type to other facilities or to patients at home due to specific negative features. Implications for manufacturers, investigators, clinicians, and administrators are identified. PMID- 2188313 TI - An update on multiple recurrent serosanguineous retinal pigment epithelial detachments in black women. AB - A unique clinical entity of multiple recurrent serosanguineous retinal pigment epithelial detachments in three black women was first described by the authors in 1985. Nine patients with this entity have now been observed, all of whom have developed a vitreous hemorrhage in at least one eye. Vitreous hemorrhage was the initial clinical presentation in seven eyes and developed 63.5 months after initial presentation in another patient who eventually sustained bilateral vitreous hemorrhages. Ultrasonographic examination in this entity often shows a characteristic pattern of irregular choroidal thickening and retinal elevation, which may aid in the diagnosis when the presentation is that of a vitreous hemorrhage of unknown origin. Vitrectomy has been performed in three cases, two of these retaining clear media during subsequent follow-up. Postvitrectomy vision correlated with the extent of macular involvement by the underlying disease. Eight patients had a history of, or evidence of, hypertension. Although choroidal neovascular membranes are a potential cause, the definitive etiology is not known. PMID- 2188314 TI - Miosis during vitreoretinal surgery. AB - Maintenance of wide pupillary dilation during vitreoretinal surgery can be important in successful completion of the operation. This study identified factors associated with intraoperative miosis. Also, flurbiprofen, a topically applied nonsteroidal anti-inflammatory agent, was evaluated for its efficacy in preventing intraoperative miosis in a prospective, randomized study of 99 consecutive patients. Factors associated with intraoperative miosis included duration of surgery greater than 90 minutes, preoperative afferent pupillary defect, and recent previous surgery. Preoperative treatment with flurbiprofen did not decrease the risk of intraoperative miosis. PMID- 2188315 TI - Giant preretinal membrane formation behind a silicone oil bubble in a hypotensive eye. AB - A patient who suffered a severe contusion injury with scleral rupture and subsequent peracute development of proliferative vitreoretinopathy was referred after wound closure at the local ophthalmology center. Initial treatment of the almost blind eye consisted of vitrectomy, silicone oil tamponade, and intraocular daunorubicin. A vitreous aspirate obtained during surgery was analyzed biochemically by electrophoresis and Western blotting. After a few days, the patient needed further surgical intervention because silicone oil was leaking through the primary sutured scleral wound. A giant fibrinous membrane extending over the posterior pole was removed. Double-label immunofluorescence examination of this specimen showed a positive reaction for transferrin, the cell surface transferrin receptor, fibrinogen, fibronectin, macrophages, and vimentin. No staining was obtained for proliferating cell antigen and T-lymphocyte antigen. The analysis of this case with a very well-defined clinical course offers valuable insight into the early stages of proliferative vitreoretinopathy. PMID- 2188316 TI - Reduction of vinblastine neurotoxicity in mice utilizing a collagen matrix carrier. AB - Vinblastine sulfate (VLB) suspended within a collagen matrix (CM) as a diffusion limiting drug delivery vehicle was examined in vitro, as well as in mouse subcutaneous and brain tumor models. Against RIF-1 and KHT subcutaneous tumors, there was enhancement of antitumor activity with intratumoral (i.t.) delivery of VLB when it was combined with CM and/or epinephrine (epi) provided as a vasoactive agent to limit diffusion of VLB away from the injection site. Furthermore, in pharmacokinetic studies an 3-fold enhancement of tumor exposure to drug (AUC) with the CM-formulation was observed relative to the administration of free VLB i.t. Craniotactic injection of VLB into mouse brain in doses from 0.2 to 2 mg/kg revealed that the CM association markedly reduced the acute toxicity of VLB in normal mouse brain. Furthermore, mice with stereotactically implanted KHT brain tumors treated with 0.2 mg/kg VLB in CM had less tumor present in the brain histologically compared to the free VLB and untreated control groups. PMID- 2188317 TI - Bacterial pneumonia in solid organ transplantation. AB - Approximately 4% of recipients of solid organ transplants in the United States develop bacterial pneumonia in the posttransplant period, often in the first 3 months following transplantation. The incidence of bacterial pneumonia is highest in recipients of heartlung (22%) and liver transplants (17%), intermediate in recipients of heart transplants (5%), and lowest in renal transplant patients (1 to 2%). The crude mortality of bacterial pneumonia in solid organ transplantation has exceeded 40% in most series. Beyond those risk factors identified for nosocomial pneumonia, the occurrence of primary cytomegalovirus (CMV) infection, graft rejection, maintenance antirejection therapy with prednisone, azathioprine, and antilymphocyte globulin, antirejection therapy with high-dose corticosteroids or OKT3 and splenectomy have been associated with a significantly increased risk of bacterial pneumonia in these patients. In the first 3 months posttransplant, gram-negative bacilli, Staphylococcus aureus and Legionella predominate and mortality is very high, in excess of 60%. Thereafter, bacterial pneumonias are caused primarily by Streptococcus pneumoniae and Hemophilus influenzae, with considerably lower mortality. Bacterial pneumonia must be suspected in any transplant patient presenting with fever and cough, especially associated with dyspnea or infiltrates on chest radiograph. If large numbers of bacteria and polymorphonuclear leukocytes are not visualized in respiratory secretions the work-up should proceed directly to fiberoptic bronchoscopy with bronchoalveolar lavage and/or protected brush specimen to establish the microbiologic diagnosis as accurately as possible. For presumptive gram-negative bacillary pneumonia, the initial regimen must be effective against Pseudomonas aeruginosa. Prevention of bacterial pneumonia in transplant patients must begin with immunization against S pneumoniae and Influenza A, and include precautions taken to prevent nosocomial pneumonia. It further may include measures to prevent CMV infection and the use of trimethoprim/sulfamethoxazole prophylaxis during the first year posttransplantation. Ultimately, novel technologies such as selective antimicrobial decontamination and/or protective isolation during the early postoperative period may prove effective. PMID- 2188318 TI - Legionella infection in transplant patients. AB - Since the discovery of Legionella pneumophila in the late 1970s, this organism and other Legionella sp have been an important cause of pneumonia in solid organ transplant recipients. Legionella sp are obligate aerobes that require a source of amino acids, iron, and L-cystine. Growth is enhanced in a 5% CO2 atmosphere at 37 degrees C in the presence of charcoal. Legionella sp reside in water supplies and hospital outbreaks associated with contaminated water have been described. Transplant recipients are particularly susceptible to Legionella infection. Legionella pneumonia tends to occur within several weeks after transplantation and frequently coincides with episodes of rejection. A prodrome of influenza-like symptoms is followed by a sometimes "explosive" pneumonia with patchy lobular or interstitial infiltrates on chest radiograph. High fever, abdominal pain, and mental status changes are sometimes seen. Diagnosis is made by examination of respiratory secretions by the direct fluorescent antibody technique or culture of the organism. Intravenous erythromycin is the treatment of choice. Rifampin is added if there is a lack of response. Both erythromycin and rifampin have important and opposite effects on cyclosporine metabolism, which may result, respectively, in increased cyclosporine toxicity or graft loss. Patients who must continue cyclosporine will, therefore, require frequent monitoring of cyclosporine levels. PMID- 2188319 TI - Mycobacterial infections in the transplant patient. AB - Mycobacterial infections in the transplant recipient differ considerably from those occurring in the normal host. The incidences of active disease, atypical disease, and extrapulmonary disease, especially dissemination, are all increased. These differences are reflected clinically in an increased mortality (30%) and a high rate (37%) of infection associated with rejection. The clinician must rely on sparse data to draw conclusions regarding prophylaxis and therapy. In general, cyclosporine-related drug interactions must be constantly monitored. Pyrazinamide should replace rifampin whenever cyclosporine is in use. Prompt recognition of the diverse presentations of mycobacterial disease and definitive diagnosis and treatment will improve outcome. PMID- 2188320 TI - Nocardiosis in transplant recipients. AB - Nocardia is an increasingly important opportunistic pathogen in immunosuppressed patients, especially solid organ transplant recipients. Infection is most often caused by Nocardia asteroides and presents as lung disease in 80% to 90% of infected transplant patients. Radiographic findings are nonspecific and include nodular infiltrates, cavitation, and pleural effusion. Dissemination to other organs, especially to the central nervous system (CNS) and skin, occurs in up to 40% of transplant recipients. A presumptive diagnosis is most rapidly made by the direct visualization in tissue, lower respiratory secretions, or wound drainage of filamentous, gram-positive, beaded rods that are partially acid fast. Specimens for culture should be held for at least 3 weeks when the diagnosis is suspected. The prognosis of nocardial infection is related to the site of disease, rapidity of diagnosis, and extended treatment with a sulfonamide. Mortality is highest in patients with CNS involvement. Prophylactic trimethoprim sulfamethoxazole should be considered in transplant centers with excess rates of nocardial infection. Hopefully, future refinement of immunosuppressive regimens will be accompanied by a reduction in frequency of Nocardia infections in transplant recipients. PMID- 2188321 TI - Fungal pneumonia in transplant recipients. AB - Fungal pneumonia is an infrequent but devastating complication of solid organ transplantation. The suspicion of fungal pulmonary infections caused by the dimorphic fungi is based on particular knowledge about the recipient's past or present residence in an endemic area. Some fungi, such as Cryptococcus neoformans, Candida sp and Mucor sp are associated with concomitant diabetes mellitus. The level of immunosuppressive therapy is also a major predisposing factor. For some fungi, such as Coccidioides immitis and C neoformans, serologic tests may assist in diagnosis. For aspergillus, Candida sp and Mucor sp culture evidence is not sufficient to determine pulmonary involvement since these fungi may be nonpathogenic saprophytes. Histopathologic proof is required. In patients with abnormal host defenses, treatment of fungal pneumonia is complex. In solid organ transplant recipients it is made more difficult by drug interactions with cyclosporine. Amphotericin B exhibits synergistic nephrotoxicity with cyclosporine and ketoconazole competes with cyclosporine for hepatic metabolism in an unpredictable manner that may result in increased cyclosporine toxicity. PMID- 2188322 TI - The historical basis of transfusion and oncologic practice. PMID- 2188323 TI - Physiology of blood and bone marrow. PMID- 2188324 TI - Incorporating historical control data in planning phase II clinical trials. AB - Phase II studies of new medical treatments often use historical data on the standard treatment for comparative evaluation. Incorrectly disregarding inherent variability in the historical data may lead to erroneous conclusions regarding the efficacy of the experimental treatment. We propose an approach to phase II trial design which accounts for both inter-study and intra-study variation. Our results indicate that it is sometimes best to randomize a proportion of the patients to a control arm. We choose this proportion to maximize the precision of the estimated experimental treatment effect. We evaluate operating characteristics of the design numerically, and provide illustrations based on historical data from cancer chemotherapy trials. PMID- 2188325 TI - Modelling peritonitis rates and associated risk factors for individuals on continuous ambulatory peritoneal dialysis. AB - A mixed effects Poisson regression model is proposed for analysing potential risk factors associated with peritonitis, a bacterial infection of the peritoneum which is common among individuals on continuous ambulatory peritoneal dialysis (CAPD). The model incorporates a set of fixed effects corresponding to concomitant information collected across individuals as well as a random effect due to individuals. The method of maximum likelihood is used to estimate the unknown parameters. When applied to clinical data obtained on 81 CAPD patients from four centres, the mixed effects model demonstrated a much better fit than the corresponding fixed effects Poisson regression model. PMID- 2188326 TI - Optimal choice of prognostic variables with an application to cardiac monitoring using M-mode echocardiography. AB - This paper provides a methodology for the optimal choice of a subset from a large number of interrelated diagnostic variables. We use predetermined abnormal ranges for each measurement and code subjects as abnormal or normal on this basis. We present a procedure to determine the smallest subset of measurements that identifies any subject abnormal on at least one measurement. We formulate and solve the problem using integer programming. We then apply this methodology to study the use of M-mode echocardiography to determine potentially cardiotoxic side effects of chemotherapy and compare its performance to several multivariate methods. Extensions and modifications are discussed. PMID- 2188327 TI - Survival analysis techniques in angina pectoris trials. AB - The variable 'walking time to moderate angina' on an exercise stress test is the primary means to judge the efficacy of new treatments for angina pectoris. Unfortunately, 'walking time to moderate angina' is often censored by fatigue or other reasons for premature termination of the exercise stress test. If time to fatigue is not treatment-dependent, we propose use of survival analysis techniques in such trials. We present an example from a placebo-controlled multicentre clinical trial and results of simulations that compare various methods of analysis. PMID- 2188328 TI - Exercise and diabetes mellitus in pregnancy. A brief review. PMID- 2188330 TI - Biomechanics of crosscountry skiing. AB - The mechanics of crosscountry skiing involve a complex interaction between the kinematic characteristics of the movement patterns and the kinetic relationships driving the motion. Crosscountry skiing techniques have been the subject of some biomechanical research, primarily involving the traditional diagonal stride technique. In the 1980s, skiers have developed several new approaches to moving across snow. These skating techniques rely on the generation of force from ski placements at an angle to the forward direction creating propulsive force while the ski slides forward. Biomechanical analysis of the crosscountry techniques has developed from rather simple 2-dimensional kinematic descriptions of diagonal stride to complex measurement of skating forces and 3-dimensional motion. The combined determination of forces and resultant motion has perhaps the most promise for practical application in assessments of equipment and technique. The relationship of the kinematic characteristics of skiing to the forces involved have received preliminary study but substantial gains in understanding will be necessary before approaches to optimising a skier's technique are plausible. PMID- 2188329 TI - Strength training and lipoprotein-lipid profiles. A critical analysis and recommendations for further study. PMID- 2188332 TI - The treatment of avulsion fractures of the tibial tuberosity in adolescent athletes. AB - Avulsion fractures of the tibial tuberosity occur mainly during sport activities and are closely related to the strains exerted on the anterior tibial tuberosity by the extension complex of the thigh. A knowledge of the mechanical aspects of these avulsions may improve understanding of the mechanisms of such injuries. In such avulsion fractures, tensile forces due to the contraction of the quadriceps complex overcome the cohesive forces within the apophyseal cartilage. A 1-month cast immobilisation on an extended knee gives good results in the management of nondisplaced fractures. In minor displacements, such immobilisations follow closed external reductions. Open reductions and stable screw fixations precede a 3-week immobilisation for displaced fractures. Long term results are regularly good in well-managed cases. PMID- 2188331 TI - Apnoeic heart rate responses in humans. A review. AB - Research examining the heart rate response of humans to apnoea and apnoeic immersion in water has tended to produce equivocal results. Controversy exists in relation to the existence and onset, course and ultimate extent of apnoeic bradycardia, either at rest or during exercise. The reduction in heart rate that has been observed in response to apnoea and apnoeic immersion is considered by some to be a component of an oxygen conserving mechanism termed the mammalian dive reflex. Doubt has been expressed, however, as to whether humans do possess the complex cardiovascular response evident in diving mammals. A bradycardial response to apnoea at rest is reasonably well established. Reports conflict with regard to apnoeic responses to exercise in both terrestrial and aquatic environments, and for the temporal onset of apnoeic bradycardia in general, and the time course required for the maximal development of the response. It is suggested that the existing discrepancies with regard to heart rate responses to apnoea are due in part to the large variety of research protocols employed, with, in many cases, a lack of control of those factors said to modify apnoeic heart rates, and in part to a lack of uniformity in the interpretation of the obtained results. Conflicting evidence exists for almost all of the factors said to modify the apnoeic heart rate response in humans. Factors implicated in the phenomenon of apnoeic bradycardia include the influence of temperature and the physical condition of the individual, varying lung volumes, the depth of immersion in water, the body position during the apnoeic episode, and the psychological state of the individual. The influence of the sex and age of the subjects is equally contentious. Finally, the role of breath-holding capacity as it influences the extent of bradycardia remains to be examined further. Additional research requires the adoption of an integrative, holistic approach if a comprehensive understanding of apnoeic heart rate responses is to be achieved. PMID- 2188333 TI - Injuries to dancers. Prevalence, treatment and prevention. AB - Studies from the USA and UK indicate that the back, neck and shoulder and the lower limb (particularly the hip, knee, ankle and foot) are the most frequent sites of injury among dancers. Most injuries are soft tissue injuries. Most dancers experience injuries at some time and about half have chronic injuries. Shoulder injuries appear to be caused by frequent or unaccustomed lifting, and are treated by rest and oral anti-inflammatory medication. Back injuries include sprains, prolapsed or herniated intervertebral discs, and spondylolytic stress fractures. Several risk factors, especially training error, have been identified for overuse injuries. Hip injuries include degenerative changes and osteoarthritis, stress fractures, bursitis and damage to the sciatic nerve. The most common foot injury is an anterior lateral ligament sprain, which may lead to permanent instability in the ankle. More soundly based research into the prevalence, diagnosis and treatment of injuries is needed. PMID- 2188334 TI - [Functional pathology of the spine and otology]. AB - The vertebral column, consisting of individual Junghann's movement segments (smallest functional units), can show functional impairment (malfunction) producing peripheral pain mostly without an organic cause. In the ENT area there are many syndromes caused by such malfunction, mostly in the upper cervical spine. Spondylogenous disorders can perhaps trigger additional nociceptive reactions. Knowledge of the functional pathology of the vertebral column and its exact diagnosis are the basis of a comprehensive treatment strategy. PMID- 2188336 TI - Cholera comes to Providence, 1832. PMID- 2188335 TI - [Hyposensitization in pollinosis. Results of a 3-year controlled study with 2 depot-allergoid grass pollen extracts: aluminum hydroxide-adsorbed allergoid and tyrosine-adsorbed allergoid]. AB - For controlled hyposensitization treatment over a period of three years 36 patients with confirmed grass pollen sensitization had been selected in 1986 and randomly distributed to receive preseasonal injection therapy: 23 patients were treated with an average of seven AGD (aluminium-adsorbed allergoid) injections, and 13 patients had received six TA (tyrosine-adsorbed allergoid) injections. Evaluation of the trial data collected during three years of preseasonal treatment showed the following results of tolerance and efficacy: Systemic side reactions registered during therapy were only mild and transient and occurred in the average after 3% of the AGD injections and after 10% of the TA injections. Local reactions over 5 cm diameter were registered after 7% in the AGD group and after 9% in the TA group. Before therapy there was no significant difference (p greater than 0.05) between the groups; after three years of therapy the AGD injections had resulted in a mean net rise of specific IgG of 220% (significant, p = 0.001); during the same time, TA injections had resulted in a final net increase of 10% (not significant, p greater than 0.05). Both treatment forms did not lead to any statistically relevant changes of specific IgE values. After three years of hyposensitization treatment, patients of both groups had improved; but an advantage was documented for patients treated with AGD on the basis of scores for objective assessment as well as for registered symptom and medication scores. PMID- 2188337 TI - Protein factor of fertility in malignancies. AB - Serum levels of the protein factor of fertility (PFF) were measured by immunoenzymatic assay with a sensitivity of 4 ng/ml. The normal concentration of PFF was within 8-20 ng/ml in males and 20-40 ng/ml in females. Elevated levels of PFF--from 50 to 400 ng/ml--were found in patients with ovarian tumors (19%), cancer of the uterine body (25%) and tumors of the uterine cervix (37%). PMID- 2188338 TI - Individualization of the cutoff value for serum squamous-cell carcinoma antigen using a sensitive enzyme immunoassay. AB - A sensitive enzyme immunoassay (IMx) for the squamous-cell carcinoma (SCC) antigen was used to evaluate low concentrations of this marker in the blood circulation. The assay can detect 0.05 ng/ml of serum SCC antigen, with intra- and interassay variabilities of 4.8 and 8.9%, respectively. Daily changes in serum SCC antigen were determined in healthy volunteers and in patients with cervical squamous-cell carcinoma after complete resection of the primary tumor, which revealed that, although the absolute values were variable from one case to another, the daily changes were relatively constant in each case, with a mean daily variation of 24.1 +/- 3.7% (mean +/- SE). The determination of the cutoff value for each individual patient may be effective for the early detection of an abnormal rise of circulating tumor marker, and will be useful in detecting small tumor foci during follow-up after treatment. PMID- 2188339 TI - [Rupture of the rotator cuff]. AB - Spontaneous or traumatic ruptures almost always occur in a cuff that has degenerated due to overuse. Despite the lack of absolute anatomico-clinical correlation, two clinical types can be described: a conflictual, often hyperalgesic shoulder with its painful arch corresponding to a small anterosuperior rupture, or a pseudo-paralytic shoulder betraying a major posterosuperior rupture. Standard radiography with Leclercq's manoeuvre is performed primarily to find out whether the cuff is continent or incontinent. Modern medical imaging (ultrasonography or MRI) adds precision to the lesions when surgery is contemplated. When medical treatment has failed, partial ruptures are treated by arthrolysis; ruptures of the superficial and deep layers of the cuff without calcification benefit from endoscopy; ruptures involving tendons or associated with calcifications are treated by surgery. Small and medium ruptures with a continent cuff require endoscopic or surgical anterior decompression combined, in cases where the intra-articular long head of the biceps is exposed, with repair, usually by suture. Extensive ruptures with an incontinent cuff are treated by muscle transfer alone of combined with arthroplasty, or by semi constrained total prosthesis when arthrosis of the humeral joint is present. PMID- 2188340 TI - [The total shoulder prosthesis]. AB - Prosthetic shoulder replacement is impeded by two main obstacles: the articular cavity is very shallow, and the small glenoid surface rests on a narrow neck to which prosthetic pieces are difficult to attach. The principal, currently used prostheses are non-retentive models which reproduce the anatomy of the joint. They differ from each other mainly in the glenoid piece pattern which may be sealed only to the glenoid cavity or also fixed onto the acromion. On the whole, the clinical results reported are encouraging, particularly as regards the absence of pain, but the radiological course of the glenoidal sealing is a source of concern. Obvious unsealing is rare, but cracks between bone and cement are very frequent and some of them become wider as time goes by. In addition, there is still no satisfactory solution to the problem of big rotator cuff tears. This type of prosthesis must be envisaged with caution and should be reserved to very painful shoulders, but it would be wise not to wait until the rotator cuff is destroyed. The best indications are glenohumeral osteoarthritis, rheumatoid arthritis and necrosis of the tumoral head. PMID- 2188341 TI - [The discovery of Yersinia pestis]. PMID- 2188342 TI - [Obstructive malformation of the lower urinary tract: the valves of the posterior urethra. Diagnosis, principles of treatment]. PMID- 2188343 TI - [Imaging of the shoulder in orthopedic pathology]. AB - Radiological examination of an unstable shoulder relies on straight X-ray images which are better than CT scans to detect bone lesions consecutive to anterior destabilizing accidents. The indications of CT arthrography are very limited. Radiological studies of the rotator cuff must necessarily include a standard radiological examination. Contrast arthrography is used either to find out whether or not the cuff is damaged, or when the tear is thought to be small. Arthropneumotomography is useful in the preoperative assessment of severe postero superior tears. CT arthrography is very good to explore the subscapular muscle and to detect medial dislocation of the biceps long head tendon. The first results of MRI are encouraging, and when the cost of this method is reduced it might replace arthrography. PMID- 2188344 TI - [Does fibromyalgia exist?]. AB - The term fibromyalgia, though often used, is not justified since no fibrosis has been shown on the histological level. The aim of this article is to make a critical analysis of the semiology usually attributed to fibromyalgias, to cite the main related syndromes whose nosology is often unclear (benign myalgic encephalomyelitis, epidemic neuromyasthenia, diffuse idiopathic multifocal pain syndrome, chronic fatigue, AMP desaminase deficiency, etc.), to prefer the purely descriptive term of "persistent, diffuse myalgia with no recognized organic etiology". According to the author's experience, a psychological etiology is detectable in only 25% of the cases. Morphological or functional muscular abnormalities are sometimes found, but their significance is not well known. A real multifactorial vicious circle partly explains the physiopathological complexity. PMID- 2188345 TI - [Does rheumatoid polyarthritis come from the New World?]. AB - While rheumatoid arthritis apparently did not exist in the Old World prior to the eighteenth century, a symmetrical erosive arthritis, indistinguishable from contemporary rheumatoid arthritis is clearly documented in the 1,000 year before present Fort Ancient-Anderson Village site. As lesions compatible with a diagnosis of rheumatoid arthritis have not been noted in the Old World prior to 1785, observation of 35 pre-Columbian cases of compatible lesions, suggests the likelihood that rheumatoid arthritis is a New World disease that subsequently spread to the Old World. Study of the geographical patterns and timing of distribution of rheumatoid arthritis and of New World organic items may provide an opportunity to identify the responsible pathogens or allergens. PMID- 2188347 TI - [The role of the condyle in the growth of the mandible and in facial balance]. AB - The condyle is not responsible for the growth of the body of the mandible, as the latter does not extend in length caudally at the expense of the ascending rami (through the classical relocation phenomenon), but does so deep to these, at the level of the lower insertions of the sphenomandibular ligaments (i.e., from the inlet inner border of the inferior dental canals). Philogenetically and ontogenetically, its appearance reflects the adaptation of the mandible of mammals to the morphologic and functional changes that took place in their cephalic skeleton (more erect posture, more vigorous mastication). Its chief role in man is to stabilize the mandibular body and to allow it to be properly mobilized, although contributing also to its forward and downward movements (namely in its posterior aspect). As such, it plays an active role in mandibular growth, and this role varies according to the primary "potential" of the condylar cartilage. Such primary-type potential for condylar growth may be adequately assessed by studying the shape of the mandible, as well as through an analysis of craniofacial architecture. Most of the conventional diagrams depicting mandibular growth are defective. Another figurative system has to be innovated, that will differentiate each skeletal unit--body, condyle, coronoid process, angle, alveolodental arch--, the sum of which confers the shape, the size, and the multiple variations to the mandible as a whole. PMID- 2188346 TI - [Management of children with chronic rheumatism. Similarities and differences with rheumatoid polyarthritis]. AB - In France, about 3,000 children under 16 years of age suffer from juvenile chronic arthritis (JCA), whose management presents a problem. JCA covers several nosological entities. In 20% of the cases, a systemic form affecting the articulations in an inconstant way, and starting in the very young child, is observed. In 30% of the cases, a form with a polyarticular start is observed. This group is very heterogeneous and includes in particular early seropositive rheumatoid arthritis (RA), the little girls' polyarthritis with presence of antinuclear antibodies, and the little boys' rheumatisms HLA B27. Finally, in 50% of the cases, an oligoarticular form is observed, also expressed in greatly varying ways. In all cases, the evolution is unpredictable and the management of these children is different from that of adults. It must be noted that the treatments used in adults are rarely applied to children as JCA is a pathology which is quite different from RA. Several types of treatment can be administered by general route: non-steroidal antiinflammatory drugs (NSAIDs) and mainly aspirin, since few NSAIDs have a paediatric licence in France. However, the risks of intolerance at doses reaching up to 100 mg/kg are not negligible. Some NSAIDs can be used in older children. The slow acting drugs are dangerous in the systemic form of JCA. Their indication seem to be more appropriate in the polyarticular forms. In the oligoarticular forms, slow acting drugs are rarely proposed. Corticosteroids are prescribed in aspirin-resistant systemic forms only. Besides the complications observed in adults, the growth is stopped in a constant way.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188348 TI - [Fractures of the mandible. A critical study of repair procedures]. AB - Based on their personal experience of 110 patients operated on for mandibular trauma, the authors analyse the results of the various techniques used. Screwed micro-plates may be very useful but only complete the therapeutic arsenal of the surgeon. In fact classical methods continue to provide satisfactory results. Poorer results may occur with fractures which combine involvement of the articular surfaces with a lesion of the body of the mandible. PMID- 2188349 TI - [Use of the conjunctival approach in orbital-palpebral plastic surgery]. AB - The conjunctival route has several indications in palpebral surgery and traumatology. After a brief anatomical summary, the authors review the principles of the technique and differentiate between the preseptal and retroseptal dissection planes. This technique has two indications: in subcutaneous lipectomy for isolated palpebral lipoptosis and in surgery involving the orbital bones, for example in osteotomies or relatively undisplaced fractures of the orbital floor. The conjunctival route has numerous advantages and enlarges the surgical arsenal of the specialist by providing another approach to the orbito-palpebral structures. PMID- 2188350 TI - [Rhino-genioplasty]. AB - The authors explain the great rules of the nose and chin interventions, isolated or combined. They dwell on the value of a strict analysis of the nose and the whole facial structures. These operations called "profiloplasty" are executed on a balanced face, regarding to its skeletal basis. PMID- 2188351 TI - [Cysts and fistulas of the 1st cleft. Apropos of 5 cases]. AB - The authors describe 5 cases of auriculobranchial anomalies, including 2 fistulas, 2 cysts, and 1 case of combined cyst + fistula of the primary cleft. They take this opportunity to review the underlying pathogenic mechanism, the clinical manifestations and therapeutic procedures. PMID- 2188352 TI - Sample, count, identify, and store the mutans streptococci. AB - According to a new method for sampling mutans streptococci, "Strip mutans", a plastic strip is contaminated by human saliva and incubated in a selective broth. After growth the strip with adherent colonies may be dried and stored. We wanted to know for how long a time bacteria in the colonies were viable if the strips were stored under different conditions. The survival time is important if the bacteria need to be subjected to further analyses. The results showed that the viability of the bacteria after the incubation period was at least 1 yr when the strips were stored frozen or frozen in glycerine. Stored dried in room temperature the survival was about 8 wk. A second part of the study aimed at identifying the colonies on strips obtained from different countries. Dried strips were sent air mail to our laboratory for biochemical and immunological analyses and the results showed that serotype/biotype c/e/f of S. mutans were most frequent but d/g S. sobrinus was also present in the samples, which came from Brazil, Greece, and Sweden. Three colonies of 213 on these strips did not grow, possibly indicating non-mutans bacteria. PMID- 2188353 TI - [Imaging of seronegative spondyloarthritis]. AB - The seronegative spondyloarthropathies (ankylosing spondylitis, psoriatic arthritis, Reiter's syndrome and arthritis associated with chronic inflammatory bowel diseases) are distinguished by inflammatory lesions of the sacroiliac joints, of the spine and/or a peripheral arthritis associated with the absence of rheumatoid factors. The author describes the radiological features of this group of diseases and their differential diagnosis. PMID- 2188354 TI - [MRI indications in the diagnosis of joint diseases]. AB - Magnetic resonance imaging (MRI) is the method of choice in depicting avascular bone necrosis, occult fractures, and internal lesions of the knee. MRI is a complementary examination in other pathologies of the joints such as rotator cuff tears, limbus lesions, carpal tunnel syndrome, and traumatic or inflammatory lesions of hand and foot ligaments. PMID- 2188355 TI - [A comparison of the adhesive strength of unaged and aged metal-resin bonding systems. An in vitro study]. AB - The tensile strength and shearing strength of six bonding systems for the acrylic resin to metal bond were tested, unaltered and after cyclic thermal shock. The methods were 1) sandblasting with 50 mu and 2) 250 mu aluminium oxide granules, 3) electrolytic etching, 4) the RBS system, 5) the Sebond-MKV system, and 6) silicoating with the Kulzer Silicoater system. The materials to bond were Paladur, an autopolymerizing methacrylate, and the cobalt chromium alloy Wisil M. It was found that sandblasting gave good constant results depending on the size of the Al2O3 granules. RBS did not improve the tensile strength. The other tested systems improved the average values by a factor 3.5 in comparison to sandblasting. Silicoating showed a wide scattered range. The values of Sebond were increased and constant. After thermocycling the values were up to 30% better, but only when the recommended opaquer was not used. Sandblasting could give a good reference as baseline for comparative studies. PMID- 2188356 TI - Skullduggery. Pundits ponder perforated prehistoric pates from Peru. PMID- 2188357 TI - GTP-GDP exchange proteins. PMID- 2188358 TI - The case of the altered notebooks: Part IV. PMID- 2188359 TI - Insights from broken brains. PMID- 2188360 TI - Interaction of Hsp 70 with newly synthesized proteins: implications for protein folding and assembly. AB - The 70-kilodalton family of heat shock proteins (Hsp 70) has been implicated in posttranslational protein assembly and translocation. Binding of cytosolic forms of Hsp 70 (Hsp 72,73) with nascent proteins in the normal cell was investigated and found to be transient and adenosine triphosphate (ATP)-dependent. Interaction of Hsp 72,73 with newly synthesized proteins appeared to occur cotranslationally, because nascent polypeptides released prematurely from polysomes in vivo can be isolated in a complex with Hsp 72,73. Moreover, isolation of polysomes from short term [35S]Met-labeled cells (pulsed) revealed that Hsp 72,73 associated with nascent polypeptide chains. In cells experiencing stress, newly synthesized proteins coimmunoprecipitated with Hsp 72,73; however, in contrast to normal cells, interaction with Hsp 72,73 was not transient. A model consistent with these data suggests that under normal growth conditions, cytosolic Hsp 72,73 interact transiently with nascent polypeptides to facilitate proper folding, and that metabolic stress interferes with these events. PMID- 2188361 TI - Genetic suppression of mutations in the Drosophila abl proto-oncogene homolog. AB - The Drosophila abelson (abl) gene encodes the homolog of the mammalian c-abl cytoplasmic tyrosine kinase and is an essential gene for the development of viable adult flies. Three second-site mutations that suppress the lethality caused by the absence of abl function have been isolated, and all three map to the gene enabled (ena). The mutations are recessive embryonic lethal mutations but act as dominant mutations to compensate for the neural defects of abl mutants. Thus, mutations in a specific gene can compensate for the absence of a tyrosine kinase. PMID- 2188362 TI - No specific recognition of leader peptide by SecB, a chaperone involved in protein export. AB - Most proteins destined for export from Escherichia coli are made as precursors containing amino-terminal leader sequences that are essential for export and that are removed during the process. The initial step in export of a subset of proteins, which includes maltose-binding protein, is binding of the precursor by the molecular chaperone SecB. This work shows directly that SecB binds with high affinity to unfolded maltose-binding protein but does not specifically recognize and bind the leader. Rather, the leader modulates folding to expose elements in the remainder of the polypeptide that are recognized by SecB. PMID- 2188363 TI - Enhancement of the GDP-GTP exchange of RAS proteins by the carboxyl-terminal domain of SCD25. AB - In Saccharomyces cerevisiae, the product of the CDC25 gene controls the RAS mediated production of adenosine 3',5'-monophosphate (cAMP). In vivo the carboxyl terminal third of the CDC25 gene product is sufficient for the activation of adenylate cyclase. The 3'-terminal part of SCD25, a gene of S. cerevisiae structurally related to CDC25, can suppress the requirement for CDC25. Partially purified preparations of the carboxy-terminal domain of the SCD25 gene product enhanced the exchange rate of guanosine diphosphate (GDP) to guanosine triphosphate (GTP) of pure RAS2 protein by stimulating the release of GDP. This protein fragment had a similar effect on the human c-H-ras-encoded p21 protein. Thus, the SCD25 carboxyl-terminal domain can enhance the regeneration of the active form of RAS proteins. PMID- 2188364 TI - Activation of ras oncogenes preceding the onset of neoplasia. AB - The identification of ras oncogenes in human and animal cancers including precancerous lesions indicates that these genes participate in the early stages of neoplastic development. Yet, these observations do not define the timing of ras oncogene activation in the multistep process of carcinogenesis. To ascertain the timing of ras oncogene activation, an animal model system was devised that involves the induction of mammary carcinomas in rats exposed at birth to the carcinogen nitrosomethylurea. High-resolution restriction fragment length polymorphism analysis of polymerase chain reaction-amplified ras sequences revealed the presence of both H-ras and K-ras oncogenes in normal mammary glands 2 weeks after carcinogen treatment and at least 2 months before the onset of neoplasia. These ras oncogenes can remain latent within the mammary gland until exposure to estrogens, demonstrating that activation of ras oncogenes can precede the onset of neoplasia and suggesting that normal physiological proliferative processes such as estrogen-induced mammary gland development may lead to neoplasia if the targeted cells harbor latent ras oncogenes. PMID- 2188365 TI - HSP104 required for induced thermotolerance. AB - A heat shock protein gene, HSP104, was isolated from Saccharomyces cerevisiae and a deletion mutation was introduced into yeast cells. Mutant cells grew at the same rate as wild-type cells and died at the same rate when exposed directly to high temperatures. However, when given a mild pre-heat treatment, the mutant cells did not acquire tolerance to heat, as did wild-type cells. Transformation with the wild-type gene rescued the defect of mutant cells. The results demonstrate that a particular heat shock protein plays a critical role in cell survival at extreme temperatures. PMID- 2188366 TI - Cell interactions in the sea urchin embryo studied by fluorescence photoablation. AB - In many organisms, interactions between cells play a critical role in the specification of cell fates. In the sea urchin embryo, primary mesenchyme cells (PMCs) regulate the developmental program of a subpopulation of secondary mesenchyme cells (SMCs). The timing of this cell interaction was analyzed by means of a fluorescence photoablation technique, which was used to specifically ablate PMCs at various stages of development. In addition, the PMCs were microinjected into PMC-depleted recipient embryos at different developmental stages and their effect on SMC fate was examined. The critical interaction between PMCs and SMCs was brief and took place late in gastrulation. Before that time, SMCs were insensitive to the suppressive signals transmitted by the PMCs. PMID- 2188367 TI - [Does sonographic evidence of blood in the abdomen following blunt abdominal trauma present an indication for surgery in every case?]. AB - In a comparative study based on the diagnosis of blunt abdominal trauma, the accuracy of ultrasound (US) proved inferior, with 82-91%, to that of diagnostic peritoneal lavage, with 97-100%. The sensitivity of US, i.e. the proportion of patients with blood in the abdomen who had an abnormal test result (positive sonography) was 94%. The reasons for this may be either patient-related (severe obesity, intestinal gas superposition) or examiner-related (differing previous experience). The specificity for correct elimination of abdominal lesions was 100%. When no intra-abdominal liquid was present none appeared in the US picture; however, 3-13% of cases where intra-abdominal liquid was present this was not revealed by US. If only a small amount of intra-abdominal liquid is demonstrated after blunt trauma, the adoption of a wait-and-see attitude is justified. In intensive care conditions US can be repeated several times if necessary. In this study US showed deterioration in these circumstances in 25%, and in 21% it must be expected that an operation will be necessary. PMID- 2188368 TI - Posttraumatic stress disorder in the police officer: paradigm of occupational stress. AB - The police officer is exposed to stress outside the range of usual human experience, which often leads to his demoralization and brutalization, and predisposes him to a posttraumatic stress disorder similar to that found in the Vietnam veteran. With posttraumatic stress disorder comes functional deterioration that can lead to significant psychologic and health problems, not only for the police officer, but also for his family. Posttraumatic stress disorder in the police officer has counterparts in other stressful occupations. Current treatment methods are outlined. PMID- 2188369 TI - Gamma knife radiosurgery: current status and review. AB - "Radiosurgery" is stereotactic neurosurgery in which the usual rigid needles or probes are replaced with beams of ionizing radiation directed toward an intracranial target so as to achieve local tissue destruction. No skin incision or skull opening is required. Lars Leksell originally defined the concept and over a prolonged research and development period created the "Gamma Knife." The Gamma Knife is a self-contained unit with 201 cobalt 60 sources arranged in a hemispheric array such that the emitted beams of radiation reach a common point of intersection. Interchangeable collimating devices allow variation of the diameter of the 50% isodose distribution from 5.0 to 24.2 mm. Larger radiation dose distributions can be achieved by multiple overlapping exposures. Initial radiation dose rate is between 300 and 400 cGy/min. Obliteration of arteriovenous malformations has been shown angiographically in 80% to 86% of optimally treated patients two years later. Growth arrest or actual decrease in tumor size has occurred in 86% of acoustic neuromas treated. Other lesions treated with the Gamma Knife have included pituitary adenomas, craniopharyngiomas, pineal region tumors, and ocular melanomas, as well as functional disorders. PMID- 2188371 TI - The two sides of worry. AB - Worry is commonly viewed as synonymous with anxiety. The majority of references to worry describe its adverse effects on health. Worry is useful as a way of coping, but has its limits. PMID- 2188370 TI - Did the Romans know about the use of forceps? PMID- 2188372 TI - Candidal meningitis following bacterial meningitis. AB - Patients with bacterial meningitis and posttraumatic and/or postsurgical access to the CSF are at risk for superinfection with Candida species. Patients who are not improving on appropriate antimicrobial chemotherapy for bacterial meningitis or are deteriorating after initial improvement should have a CSF reexamination for Candida superinfection. PMID- 2188373 TI - Wernicke's encephalopathy manifested as Korsakoff's syndrome in a patient with promyelocytic leukemia. AB - A case of Wernicke's encephalopathy associated with promyelocytic leukemia found at autopsy is reported. The patient was 30 years old and was undergoing chemotherapeutic treatment when she had a memory deficit for recent events (Korsakoff's syndrome) which persisted for 6 months, until death. The neuropathologic examination showed typical, old lesions that characterize Wernicke's encephalopathy, but only in the mamillary bodies. This case is compared with three other cases of Wernicke's encephalopathy associated with leukemia previously described in the literature. Comment is made on the cliniconeuropathologic picture and risk factors in leukemic patients that may favor the appearance of Wernicke's encephalopathy. PMID- 2188374 TI - Management of blunt hepatic duct transection by ligation. AB - We have reported a case of blunt trauma causing major hepatic injury and disruption of the right hepatic duct. The patient was treated with resectional debridement and ligation of the right hepatic duct; he has done well, without jaundice or signs of hepatic dysfunction. We recommend lobar hepatic duct ligation when other more conventional avenues such as primary repair or biliary enteric anastomosis are precluded by hemodynamic instability or a nonreconstructable duct. PMID- 2188375 TI - Septic sacroiliitis due to Proteus mirabilis. AB - This case demonstrates the difficulty frequently encountered in making an early diagnosis of septic sacroiliitis. The proper use of appropriate laboratory tests and radiologic examinations can narrow the differential diagnosis significantly, with confirmation resting on culture results. Appropriate antibiotic therapy will depend on the organism isolated. When confronted by the typical clinical findings and supporting ancillary data of septic sacroiliitis, the physician should consider the possibility of an unusual organism such as Proteus mirabilis and should direct antibiotic therapy accordingly. PMID- 2188376 TI - Does the presence of hepatic portal venous gas mandate an operation? A reassessment. AB - The presence of HPVG has been said to constitute a mandatory indication for exploratory laparotomy, given the high incidence of concomitant bowel necrosis and abdominal sepsis. HPVG has also been associated with increased intraluminal pressure in the absence of bowel ischemia. Most cases are iatrogenic, usually due to barium enema or colonoscopy in patients with inflammatory bowel disease, but in a few cases, HPVG is associated with simple intestinal or gastric distention. The English literature on the subject describes only eight such cases. We recently treated a patient in whom HPVG was caused by intestinal pseudo obstruction. Such an etiologic mechanism has not been previously reported. The relevance of this observation and a reassessment of the absolute obligation to operate prompted this review. PMID- 2188377 TI - Reversible leukopenia related to ciprofloxacin therapy. AB - In general, ciprofloxacin is well tolerated. The most common adverse effects are nausea, vomiting, diarrhea, dizziness, nervousness, and rash. Reversible leukopenia can be associated with the use of oral ciprofloxacin, as shown by our case. Leukopenia should be watched for as the use of this drug increases. PMID- 2188378 TI - Hypertension as an insulin-resistant state. A newly discovered concept. PMID- 2188380 TI - Pseudomonas septicaemia after endoscopic retrograde cholangiopancreatography--an unresolved problem. AB - Over a 6-month period 5 patients with obstructive jaundice developed Gram negative septicaemia, all within 48 hours of undergoing endoscopic retrograde cholangiopancreatography. The sepsis proved fatal in 3 patients, despite prompt decompression of the obstructed biliary system. In all cases the organism responsible was Pseudomonas aeruginosa and the source of infection appeared to be a contaminated water-bottle attached to the endoscopic apparatus. This report highlights the importance of disinfection techniques and reviews the present situation in respect of antibiotic prophylaxis. PMID- 2188379 TI - Bezafibrate and simvastatin (MK-733) in the treatment of primary hypercholesterolaemia. AB - Simvastatin, a new 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitor, was compared to bezafibrate, a fibric acid derivative, in an open cross-over placebo-controlled study. Bezafibrate was administered as a 200 mg dose 3 times daily, while simvastatin dosage ranged from 10 mg to 40 mg once daily at night. Bezafibrate produced a non-significant 13.1% (P = 0.113) decrease in total cholesterol (TC), a 20.7% (P less than 0.05) decrease in low-density lipoprotein cholesterol (LDL-C), an increase of 26.5% (P less than 0.01) in high-density lipoprotein cholesterol (HDL-C) and an improvement in the HDL:LDL ratio of 77.3% (P less than 0.01). Simvastatin 10 mg and 20 mg daily reduced TC by 18.6% and 22.6%, respectively, and LDL-C by 23.9% and 28.6% respectively (P less than 0.01), while no significant increase was noted in HDL-C. Simvastatin 40 mg daily reduced TC and LDL-C by 27.1% and 37.6%, respectively (P less than 0.01), increased HDL-C by 32.0% (P less than 0.05) and improved on the HDL:LDL ratio by 130.8% (P less than 0.01). This showed improvements over bezafibrate of 13.5% for TC, 18.9% for LDL-C, 6.0% for HDL-C and 55.8% for HDL:LDL ratio. It was concluded that simvastatin was well tolerated and had significant hypocholesterolaemic effects when taken once daily. PMID- 2188381 TI - [Results of the use of the Austin Moore prosthesis for the treatment of femur neck fracture at Tygerberg Hospital. A retrospective study]. AB - A retrospective study was done on 116 patients who received an Austin Moore prosthesis at Tygerberg Hospital between 1982 and 1983. The patients all had displaced intracapsular femoral neck fractures (Garden type III and IV). Although the Moore prosthesis must be fitted meticulously for good results, the operation can be performed effectively by the less experienced surgeon. This cementless monoprothesis is a good option for the elderly and/or poor-risk patient with a limited life expectancy. It has a low intraoperative mortality, a low percentage of re-operation and results in early and good mobilisation. In contrast to series on cemented prosthesis, we had a very low sepsis rate. In comparison to a total hip replacement, this is a much cheaper prosthesis and operation. PMID- 2188382 TI - [Water fluoridation as a public health measure. A sociopolitical perspective]. AB - This review provides a perspective on water fluoridation as a public health measure and the sociopolitical disputes preventing its implementation. Notwithstanding its world-wide recognition as a safe, efficient and cost effective public health measure, water fluoridation has increasingly found itself in the sociopolitical arena. Factors responsible for preventing the implementation of water fluoridation include public sensitivity, anti fluoridation campaigns, negative reporting by the media, public debates and lack of professional involvement. Successful implementation of water fluoridation can only be achieved by a purposeful national strategy, active communication and involvement by all concerned. PMID- 2188383 TI - The origin of the Public Health Act of 1919. AB - South Africa's first national public health measure was passed in 1919, just over 70 years ago. Attempts to enact such legislation in the years immediately after Union had been thwarted by vested interests and it was only the effects of World War I and, more particularly, the dire Spanish influenza epidemic of 1918, which forced Parliament to pass this pioneering measure in June 1919. It remained South Africa's basic public health measure until 1977. PMID- 2188384 TI - Effect of somatostatin analog on peptide release and tumor growth in the Zollinger-Ellison syndrome. AB - The clinical presentation of Zollinger-Ellison syndrome (ZES) is the result of gastrin hypersecretion and may be modified by secondary peptide hypersecretion. Treatment is medical (H2-blockers) or surgical (tumor excision and total gastrectomy). H2-blocker escape occurs up to 23 per cent and surgical mortality ranges to 15 per cent. Treatment of advanced disease has limited success. Sandostatin (SMS 201-995) has been shown to decrease basal gastrin and gastric acid secretion in ZES. We hypothesized that SMS would suppress basal and provoked gastrin and secondary peptide secretion in ZES. A patient with refractory, metastatic gastrinoma underwent provocative testing (test meal, calcium infusion, secretion bolus and tolbutamide bolus). Thirteen peptides were drawn at set intervals during these provocative tests. Testing was repeated during SMS therapy (100 micrograms subcutaneously three times per day). Gastrin, pancreatic polypeptide (PP) and glucagon levels were elevated at baseline. SMS suppressed all three peptides (mean 74 per cent) (p less than 0.05). Gastrin, PP and glucagon were provoked by all four tests (means above baseline, 19, 155 and 138 per cent, respectively). Gastrin-releasing peptide, gastric inhibitory peptide and insulin were provoked by calcium infusion (427, 306 and 162 per cent above baseline, respectively). SMS suppressed 14 of 15 of these peaked-provoked peptide levels (mean 72.5 per cent, p less than 0.05). Gastric analysis during calcium infusion showed SMS suppression of hourly gastric secretory volume by 77.5 per cent and of acid production (milliequivalents of acid) by 87.5 per cent. During a 20 month follow-up period, the patient was maintained on SMS, 200 micrograms subcutaneously three times per day. She has remained asymptomatic. Interval peptide profiles at two, eight and 18 months show normal gastrin, PP and glucagon levels. A computed tomographic scan at eight months shows a remarkable regression of primary and metastatic tumor. Regrowth, however, was noted at 19 months. SMS may be useful in ZES by suppressing basal and provoked gastrin and secondary peptide secretion and may occasionally give palliation by yielding temporary tumor registration. PMID- 2188385 TI - Scar endometriosis. AB - Scar endometriosis is a rare entity most commonly seen after surgical treatment of the uterus or fallopian tubes. We report three additional instances of scar endometriosis after cesarean sections as well as a patient who had synchronous scar endometriomas at separate surgical sites. PMID- 2188386 TI - Surgical separation of conjoined twins. AB - The studies and their sequence should be carefully planned based on the type of fixation, associated anomalies and need for immediate separation. The current excellent outcomes, even in difficult cases of conjoined twinning, suggest that separation should always be considered, with rare exception. Carefully planned and rehearsed operations approached by a team of surgeons, anesthesiologists and skilled nurses should yield a high success rate in separating conjoined twins who otherwise would lead a life of ridicule and deformity. PMID- 2188387 TI - Operating microscope-induced retinal phototoxicity: pathophysiology, clinical manifestations and prevention. AB - Retinal light damage is a poorly understood phenomenon, due to its multifactorial etiology and relatively infrequent recognition. It has been increasingly identified following ocular surgery involving the intense light of the operating microscope. The authors describe the clinical entity, review salient features of its pathophysiology and provide guidelines for prevention of retinal phototoxicity. PMID- 2188388 TI - Juvenile arthritis and uveitis. AB - The association between juvenile arthritis and uveitis is reviewed. Some children with the HLA-B27 related spondyloarthropathies develop anterior uveitis. About 20% of patients with juvenile rheumatoid arthritis (JRA) who are negative for IgM rheumatoid factor develop a frequently bilateral, nongranulomatous chronic anterior uveitis. Risk factors for uveitis in JRA patients are: female gender, pauciarticular onset of arthritis, presence of circulating antinuclear antibodies, and the antigens HLA-DW5 and HLA-DPw2. Uveitis is rare after seven years or more have elapsed from the onset of arthritis. The visual prognosis in patients with uveitis is good in 25% and fair in 50%. The remaining 25% develop visual impairment from complicated cataract and/or secondary inflammatory glaucoma. The potential benefit of cytotoxic agents in the treatment of intractable uveitis is outweighed by the risk of serious side effects. The management of secondary inflammatory glaucoma is unsatisfactory, but the results of treatment of complicated cataracts by lensectomy-vitrectomy are good. PMID- 2188389 TI - Corrective measures for myopia. AB - Many myopic people, expressing dissatisfaction with traditional methods of optical correction, are interested in a permanent correction of their refractive error which would alleviate dependence on corrective lenses. Although much effort has been put forth in the last century, there is still no method of correcting myopia which is broadly acceptable as safe and effective. The nonsurgical procedures of orthokeratology and the topical use of cycloplegics have not been well proven. Surgical measures are the current vectors of hope. Surgical procedures on parts of the eye other than the cornea have proven to be difficult. Surgery which alters the refractive power of the cornea (refractive keratoplasty) has been used frequently in the past decade. These procedures include keratomileusis, epikeratophakia and radial keratotomy. The latter is currently the most often performed method for the correction of myopia. This paper critiques the major methods, explains their historical development and basic procedures, lists major published studies and discusses their problems and promise for their future. PMID- 2188390 TI - William Ellergy Briggs: pioneer of west coast ophthalmology. AB - William Ellergy Briggs was California's preeminent ophthalmologist for more than fifty years. A student of Ernst Fuchs, he was a clinician, scholar, and innovator who transplanted the best of European ophthalmology to the Western United States. PMID- 2188391 TI - From Vienna to Iowa: an ophthalmologic odyssey. AB - In a warm and personal memoir, a world renowned ophthalmologist recounts experiences from his medical school days in pre-war Austria, through the tense and chaotic years of World War II, and the years of learning, practicing, and teaching in New York and Iowa after his immigration to the U.S.A. Special attention is given to the friends and colleagues who shaped and enhanced the author's career. PMID- 2188392 TI - [For a little common sense and fantasy in the Council for Ethics]. PMID- 2188393 TI - The medical liability insurance crisis: how it began. AB - Economic pressures, awareness that physicians can be sued, improved medical care, and increased patient expectations have led to the skyrocketing liability insurance costs physicians face today. In the early days when the doctor could offer hope but little medicine, patients were not inclined to sue for medical "failures." But with the Great Depression, World War II, more recent medical advances changed the patient-physician relationship. Patients had gained the expertise of specialists, but often lost the personal relationship they once shared with their primary physician. Thus, when treatments were unsuccessful, the patient often-times blamed the physician. Insurance premiums (and patient costs) increased, while patients became even more aware that physicians were covered by insurance. This article reviews key economic, medical, and social events that led to the present medical liability insurance crisis. PMID- 2188394 TI - [The future of vaccines: recombinant DNA vaccines]. AB - Classical approaches to the development of vaccines have provided mankind with a number of safe and effective vaccines (think of the world-wide eradication of smallpox). Nevertheless, some obstacles e.g. the production of a safe Hepatitis B vaccine, could not be taken by classical techniques. In several cases, recombinant-DNA technology provided an elegant solution, though in other cases, this technique also failed. The present paper presents a brief review of the role of recombinant-DNA technology in the current development of vaccines. PMID- 2188395 TI - Alloreactivity: allogeneic presentation of endogenous peptide or direct recognition of MHC polymorphism? A review. PMID- 2188396 TI - Identification of a CD4 homologue in the cat. AB - Monoclonal antibody, Fel 7, produced against cat T cells, was found to react with a single-chain glycoprotein of Mr 65,000 present on a majority of the thymocytes, 40% of lymph node cells, 15% of splenocytes and 25% of blood mononuclear cells. Using a previously reported antibody that recognizes the feline CD8 antigen, approximately 65% of cat thymocytes were shown to express both the Fel 7 and fCD8 antigens, while 14% and 6% expressed either the Fel 7 or the fCD8 determinant respectively. The Fel 7 and fCD8 antigens were expressed by mutually-exclusive subpopulations of peripheral T cells, and not by B cells, macrophages or other types of blood cells. Expression of the Fel 7 antigen was down-regulated and the molecule was phosphorylated when T cells were stimulated with phorbol ester, while the expression of the fCD8 antigen was unaffected by this treatment. The addition of soluble Fel 7 antibodies efficiently blocked Con A-induced proliferation of T cells in a dose-dependent manner. The data suggest that the mAb Fel 7 identifies a feline CD4 homologue, providing an important reagent for the study of normal and abnormal T cell development in cats. PMID- 2188397 TI - The search for chelate antagonists for chronic cadmium intoxication. AB - Cadmium is unique among the metals because of its combination of toxicity in low dosages, long biological half-life (of about 30 years in humans), its low rate of excretion from the body and the fact that it is stored predominantly in the soft tissues (liver and kidney). There has been an increase in exposure to cadmium because its presence in fertilizers and sewage sludge and also its increased industrial use in Cd-Ni batteries. Although there are a number of reports on occupational and environmental exposures to cadmium compounds, treatment of cadmium poisoning has been difficult because there is neither a safe practical means of evaluating bioavailable body burden nor is there a recommended therapeutic chelating agent for chronic cadmium intoxication. In this review, the various factors affecting the chelation of cadmium such as its binding to intracellular metallothionein, the structural requirements of compounds for effective removal of cadmium, the excretion pattern of cadmium after its mobilization from intracellular stores and the recent developments in the design and synthesis of new compounds for cadmium chelation are discussed. The importance of protecting sensitive organs such as kidney and brain during cadmium chelation is addressed. The progress made during the last decade on the synthesis of new compounds, especially derivatives of dithiocarbamates, is remarkable. Some of these compounds provide promise for development of a useful and safe therapeutic chelating agent which can be used for the assessment of cadmium body burden and for preventive removal of cadmium as well as for use in overt cadmium poisoning in humans. PMID- 2188398 TI - Characterization of the venom from Crotalus molossus nigrescens Gloyd (black tail rattlesnake): isolation of two proteases. AB - The venom from Crotalus molossus nigrescens contains many activities including: hyde powder azure proteinase; N-benzoyl-arginine-ethyl-ester hydrolase; phospholipase; phosphodiesterase; desoxyribonuclease; fibrinogen coagulase; collagenase, fibrinolytic activity, and hemorrhagic factors. The venom, assayed with amounts of venom up to 50 micrograms protein per assay, does not contain acetylcholinesterase, phosphatase, amylase, ribonuclease, tyrosyl-ester hydrolase or hyaluronidase activities. The venom is lethal to mice with an i.p. LD50 of 2.35 mg/kg mouse. Fractionation of soluble venom by Sephadex G-75 separates at least five families of components. Fractions I-III contains all the enzymes, and fraction V have six small peptides. Further separation of fractions II-III on diethyl-amino-ethyl-cellulose columns at pH 8.0 and 8.3 gave pure proteinase E with a mol. wt of 21,390 and the following N-terminal amino acid sequence; Phe Ala-Lys-Arg-Tyr-Val-Glx-Leu-Val-Ile-Val-Ala. A thrombin-like enzyme with a mol. wt of 75,000 was also purified from this venom by means of affinity and ion exchange chromatographies. PMID- 2188399 TI - m-CPP: a tool for studying behavioural responses associated with 5-HT1c receptors. PMID- 2188400 TI - Alzheimer's disease: is there a problem beyond recognition? PMID- 2188401 TI - Role of phosphorylation in desensitization of the beta-adrenoceptor. AB - Regulation of receptors allows their responses to be modified rapidly and appropriately according to the needs of the environment. Multiple mechanisms are involved in the loss of sensitivity that follows exposure to agonists. Receptor sequestration, a rapid and transient event, and receptor downregulation, which requires more prolonged agonist exposure, contribute to this effect. However, in this article Bob Lefkowitz and colleagues focus primarily on the recent developments in understanding mechanisms of rapid desensitization involving receptor phosphorylation. Various molecular biological techniques have been used to demonstrate the important roles of two particular kinases--beta ARK and protein kinase A--in this regard. PMID- 2188402 TI - Synthetic peptide vaccines against pathogens and biological mediators. AB - Recent advances in immunology and biotechnology have opened the way for new approaches to vaccine design. Gilles Riveau and Francoise Audibert discuss progress in the design of synthetic peptide antigens for vaccines against pathogens, and discuss the possibility that such vaccines could also be used to control the activity of endogenous mediators. PMID- 2188403 TI - Targets and strategies for the antiviral chemotherapy of AIDS. AB - Eradication of human immunodeficiency virus (HIV) from infected cells or organisms has remained an elusive goal. In principle, any of the steps in the replicative cycle could form the basis for rational design of chemotherapeutic agents, although in practice not all have so far proved amenable to intervention. Here, Erik De Clercq summarizes the strategies that are being employed, focusing primarily on recent promising developments in inhibition of adsorption of HIV onto CD4+ T cells, and inhibition of the viral reverse transcriptase. PMID- 2188404 TI - [Cannulation of the radial artery. Risks, effective examination methods and monitoring of the circulation in the hand during the procedure]. AB - Cannulization of the radial artery with the object of continuous measurement of the blood pressure or repeated analyses of the arterial blood gases is an easy and relatively safe procedure. Thrombosis is observed in 25-40% of the cases. The frequency depends upon the condition of the patient, the cannula and technique of cannulization and duration of this. Permanent ischaemic damage resulting from thrombosis is, however, rare. Other complications of clinical significance are infections and vascular lesions which are, similarly, rare. Allen's test for assessing the collateral circulation of the hand has a high negative predictive value while the positive predictive value is so low that a positive test result does not exclude cannulization. In these cases, better assessment of the perfusion of the hand may be obtained by combining the test with pletysmography. After cannulization, it should be possible to monitor perfusion distal to the site of cannulization employing more recent pulse oximeters with the aid of the pletysmographic curve. PMID- 2188405 TI - [Urethral stricture]. AB - The incidence of urethral stricture has increased since the introduction of gonorrhoea to Europe in the 15th century. Nowadays, transurethral instrumentations and catheterisations are responsible for the majority of the urethral strictures. The mechanism is inflammatory or traumatic lesion of the urethral epithelium causing extravasation of urine and fibrosis. The symptoms often suggest to infravesical obstruction. The diagnosis is made from the patient's history in combination with flowmetry, ante- and/or retrograde urethrography, external ultrasound examination or urethral calibration and is verified at urethroscopy. Dilatation is relatively simple but seldom curative and carries a considerable morbidity. Urethrotomy is very common but also hampered with a high rate of recurrence. A technique where urethrotomy is followed by intermittent self-catheterisation or implantation of a selfexpanding wire netting seems promising but needs further investigation. Reconstructive operations in form of a free or pedicled skin island patch, skin tube graft, endourethral free split skin graft, multistaged urethroplasty, meatoplasty and excision of prostatomebraneous stricture are followed by cure in 50-95% of the cases. PMID- 2188406 TI - [Qualitative determination of U-pregnanediol-3 alpha-glucuronide in 5 minutes. A clinical trial of a new matrix cushion test]. AB - We have tested an easy and rapid "matrix cushion test" for qualitative determination of U-pregnandiol-3 alpha-glucuronide (U-PGD). The specificity of the test is high, the sensitivity is 4.0 microM, the inter-analysis variation is low as in 96% of the double determinations, agreement was present between the first and second analyses. A positive result on the 21st of the menstrual cycle indicates that ovulation has occurred while this cannot be exluded by a negative or doubtful result. If demonstration of a functioning corpus luteum is also required, the urine should be diluted 1:2 with tap water. PMID- 2188407 TI - [Meningococcal infection and arthritis]. AB - Arthritic manifestations in patients with meningococcal disease are of varied pathogenesis. Four different pathogenic mechanisms may be involved. Direct bacterial invasion of the synovium and multiplication within the joint (septic arthritis); hypersensitivity reaction or allergic arthritis; intra- or periarticular hemorrhage (hemarthrosis) and iatrogen causes, i.e. reaction to antimicrobial agents, serum therapy etc. Four distinct clinical forms have been described: The septic, culture-positive polyarthritis is seen early in the course of the disease. The sterile "non-infectious" or allergic mono- or oligo arthritis are seen later in the course. Primary meningococcal arthritis. Arthritis may be seen in relation to chronic meningococcemia. Treatment consists primarily of specific antimeningococcal chemotherapy, viz penicillin and non-steroid-anti inflammatory drugs. The prognosis of meningococcal arthritis is excellent and joint sequelae are rare. Predisposing factors in relation to meningococcal disease are reviewed. The most important are socioeconomic conditions, acute respiratory illness, particularly in relation to age as children less than two years are most susceptible, passive smoking, IgA blocking antibodies, the concentration of complement factors C3, C6, C7, C8, and IgG2-defects. PMID- 2188408 TI - [The significance of incorrect spray technic on the consumption of terbutaline in patients with chronic obstructive lung disease]. AB - A total of 140 patients with chronic obstructive pulmonary disease was included in this multicentre parallel group investigation with the object of assessing whether poor inhalation technique results in increased consumption of beta 2 agonist. On the basis of measurements of pulmonary function, the patients were stratified into two groups with good and poor inhalation techniques, respectively, and these were subdivided at random to inhalation of terbutaline via either a freon spray (aerosol) or Turbohaler (powder). During a period of four weeks the daily terbutaline consumption, the symptoms and pulmonary function were noted. Patients with poor inhalation technique did not have significantly increased terbutaline consumption. The consumption of terbutaline was independent of the method of administration. The Turbohaler was just as effective as the spray and the patients preferred this method, (p less than 0.05). PMID- 2188409 TI - [Maternal hemodynamic monitoring in severe pre-eclampsia]. AB - Based on a review of the literature, hemodynamic signs and measurements in severe preeclampsia are described. Advantages and disadvantages of various hemodynamic methods and resulting indications for therapy are discussed. We found that in respect of hemodynamic monitoring in severe preeclampsia there are no indications for central venous pressure and conclude that at present there is no alternative to right heart catheterization (Swan-Ganz catheter). PMID- 2188410 TI - [Treatment with rectal diazepam or acetylsalicylic acid in effervescing tablets in ambulatory cervical curettage and biopsy. A double-blind randomized study]. AB - A double-blind randomised investigation with placebo control was undertaken to investigate the effect of 10 mg diazepam rectally or 1 g acetyl salicylic acid as effervescing tablets on pain and nervousness during and after outpatient cervical curettage and biopsy from the vaginal cervix or the cervical endothelium. A total of 97 women participated and were subdivided at random. Three patients were, however, excluded as they did not participate as planned. No differences were found between the three groups as regards pain and nervousness during the intervention and fatigue and drowsiness after the intervention. No statistically significant difference was found in the degree of satisfaction with the treatment in the various therapeutic groups. PMID- 2188411 TI - [Epidemiologic study of persons having group 2 insurance in Denmark. 1. Historical development, social and demographic differences between health insurance groups 1 and 2]. AB - The majority of adults in Denmark can choose between the forms of health insurance 1 and 2. Persons insured in Group 2, on payment of a premium, obtain certain perquisites as compared with Group 1, primarily they may consult general practitioners and specialists of their own choice. Since the introduction of the Health Insurance Law in 1976, the number of persons insured in Group 2 has decreased to 3.8% of those insured in 1988. More than 3/4 of these have been insured in Group 2 since 1976. The number of new group 2 insured persons has remained relatively stable at about 3,000 persons per annum. The average age in Group 2 is 58.3 years as compared with 45.0 years in Group 1. 60% live in the region of the capital. The number of economically and socially well established persons in Group 2 is markedly higher than in Group 1, particularly in the higher age groups where the mortality in Group 2 insured persons is considerably lower than in Group 1 insured persons. PMID- 2188413 TI - Growth of salmonellas in intact shell eggs: influence of storage temperature. PMID- 2188412 TI - [Salmonella typhimurium meningitis during the neonatal period]. AB - Salmonella meningitis is rare. A case of Salmonella typhimurium meningitis in an infant aged eight days is presented. The infant was probably infected during delivery. The infant survived with severe neurological sequelae. Recurrence of excretion of Salmonella typhimurium in the faeces occurred after withdrawal of antibiotic therapy and, after nine months, Salmonella typhimurium was still excreted in the faeces. PMID- 2188414 TI - Factors responsible for the introduction and spread of Campylobacter jejuni infection in commercial poultry production. AB - Campylobacter jejuni and related thermophilic campylobacters were not found in a hatchery or in chicks aged less than seven days. However, an increasing proportion of chicks aged two weeks and older shed campylobacters in their droppings. It was shown that a likely source of C jejuni for young chicks was the environment in the immediate vicinity of the rearing houses, and that infection could readily be introduced on the footwear and clothing of farm staff. Thermophilic campylobacters were found in the air, litter and drinking water containers in the rearing and finishing houses. PMID- 2188415 TI - Antibody response and duration of latent infection in sheep following experimental infection with Babesia ovis. AB - Babesia ovis isolated in Extremadura (Spain) was the subject of a serological study in experimentally inoculated sheep. The first antibody titres, determined by the indirect fluorescent antibody (IFA) test, were observed 7-8 days post infection (p.i.) in all animals except the splenectomized group, in which the only animal that survived showed antibody response 10 days p.i. A faster response following challenge was observed in sheep which were seropositive before inoculation, which suggests the existence of an antigen memory. The highest titres were reached 16-25 days p.i., and subsequently began to fall, reaching minima at the end of the experimental period (330 days p.i.). The chronic carrier state in experimental B. ovis infection had a duration of at least 2 years. Passive transmission of antibodies from experimentally infected mothers to newborn lambs was also detected. Antibody levels were observed for a period not longer than 2 months after birth. PMID- 2188416 TI - [The heroism of the medics of the military ambulance trains from an evacuation distributing center]. PMID- 2188417 TI - [The contribution of the scientists of the Red Army's Medical Research and Testing Institute to improving the material outfitting of the medical service]. PMID- 2188418 TI - [The price of careless planning (from the experience in organizing medical support for the 7th Guards' Army in the Kirovograd offensive operation)]. PMID- 2188419 TI - [Genetic engineering in modern medicine]. PMID- 2188420 TI - [The continuous loop suture]. PMID- 2188421 TI - [Morbidity on the atomic submarines of the USA]. PMID- 2188422 TI - [The immotile cilia syndrome]. PMID- 2188423 TI - [The military medical school during the National War of Liberation in Yugoslavia]. PMID- 2188424 TI - [Genetic complementation in the study of mechanisms of inborn errors of metabolism in man (review of the literature)]. AB - Application of genetic complementation procedure for evaluation of heterogeneity and development of a number of human inherited impairments, particularly, lysosomal storage diseases, are reviewed. The genetic complementation procedure is involved in cytobiochemical diagnosis of a number of enzymopathies as well as in studies of subunit containing enzymes reconstruction and their function. PMID- 2188425 TI - [The nature of angiogenic factors (review of the literature)]. AB - Literature data on angiogenic factors inducing neovascularization of both tumors and normal tissues are reviewed. Properties and structure of the factors isolated from tumors and non-tumoral tissues are considered. Multiple molecular forms of the angiogenic factors are discussed based on the data obtained as well as on analysis of these factors isolation. Acid proteinases appear to be responsible for this multiplicity. Possible fragmentation of the angiogenesis factors by means of proteinases is considered using as an example the factors isolated from brain and hepatoma tissues. PMID- 2188426 TI - [The role of kallikrein-kinin system components in the pathogenesis of bullous skin lesions in pemphigus and pemphigoid]. AB - Importance of kallikreinogenases in acantholysis and epidermo-dermal separation was shown, when the kallikreinkinin patterns were studied in blood plasma and blister fluids of 118 patients with pemphigus, of 78 patients with pemphigoid as well as of 224 guinea pigs. Under conditions of pemphigoid, as distinct from pemphigus, serine proteinases were mainly produced by active immunocytes responsible for destruction of epidermal basement membrane; activation of kinins was observed in skin impairments. PMID- 2188427 TI - [Solid phase fluorescence immunoassay of digitoxin]. PMID- 2188428 TI - [The state and possible mechanisms of impairment of oxygen-dependent processes in burns (review of the literature)]. PMID- 2188429 TI - [Membrane component of Shigella flexneri and their relationship to bacteria antigenicity and virulence]. AB - Our previous works have shown that membrane proteins of S. flexneri can elicit protection against the bacteria in vivo. In this study, we further, using human convalescent sera (HCS) from adult patients infected with S. flexneri, investigated the relationship between membrane components of S. flexneri and their antigenicities and virulences. It was shown in immunoblotting that 5 virulent strains of S. flexneri and avirulent strain T32 derived from S. flexneri 2a by Istrati in Romania and used as a live vaccine, had three common proteins bands formed by the components of MW 67 kD, 63 kD and 60 kD with either HCS from patients infected with S. flexneri 2a and 3a or HCS absorbed by an avirulent variant strain 24570 of S. flexneri 2a, while virulent strains M90T and M25-8A (pWR110)minI shown another two bands of Mw 78 kD and 35 kD respectively. In contrast, no band was found with strain 24570. HCS from patients infected with S. flexneri 1a, 2a and 3a as well as those HCS absorbed by 24570 had blocking effect on the invasiveness of virulent strain of S. flexneri to the kerato conjunctiva of guinea pigs; nevertheless, HCS absorbed by T32 lost the blocking effect accompanied by disappearance of 67 kD, 63 kD and 60 kD components when T32 was used as antigen indicating that 67 kD, 63 kD and 60 kD membrane components of S. flexneri may account for the antigen of S. flexneri eliciting protection antibodies in vivo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188430 TI - [Study on identification for the motility and flagella antigen of four international reference strains of Escherichia coli]. AB - Authors identified four strains of Escherichia coli from Collaborative Centre for reference and research on Escherichia coli-Klebsiella (WHO) in Denmark. Our results were different from original record and reference. It was shown that strain H311b and H5 were motile strains, and its H antigen respectively is H11 and H27. The strain W27 is nonmotile. H antigen of the strain H511 is H40, not H8. Antigen formula of four strains respectively is 26:60:11 (strain H311b), 81:97:27 (strain H5), 115:-:- (strain W27), 102:-:40 (strain H511). PMID- 2188431 TI - Learning disabilities and behavioural problems in children with epilepsy. AB - Children with epilepsy, as a group, are at special risk of developing learning and behavioural problems, but many individual biological and environmental factors are contributary. In general, 60% of children with epilepsy have normal intelligence. The intellectual capacities are determined by genetic factors, by frequency of fits and type of epilepsy, and, especially by the presence of brain damage. In cases with learning disabilities, difficulties with written or spoken language memory disorders or behavioural disturbances, left temporal lobe epilepsy is found to a greater extent than expected. Many behavioural traits described in the so-called epileptic personality can also be encountered in non epileptic persons, and, therefore, are non-specific. Confronted with learning and behavioural problems in children with epilepsy it can be stated that, in general, brain damage is more important than transient epileptic dysfunctions. Because many aspects of cognitive and emotional behaviour are more or less influenced by antiepileptic drug treatment, one should be very careful in prescribing drugs for chronic use in a developing individual. As important as the organic aspects are the many non-organic or psychological factors. Non-acceptance, misunderstanding and frustration of the parents have a direct impact on the self-concept of the child with epilepsy. PMID- 2188432 TI - [Hip screening in newborn infants. Clinical and ultrasound results]. AB - A routine orthopaedic examination of each newborn was performed at the Salzburger Landesfrauenklinik (Department for gynaecology and obstetrics) since 1964. The results of these examinations were stored in an electronic database since 1978 and were now evaluated in a retrospective analysis. The examinations were performed by 8 orthopaedic surgeons between I/1978 and IX/1984. 5.9 percent of all newborns had a limited abduction and 13.2 percent a lax hip. Hips with limited abduction and lax hips were not classified as pathological but were recommended for strict observation and X-ray control at an age of four months. A similar rate of instable hips such as subluxatable (= 2.11%) and luxatable (= 0.63%) hips were also observed by other authors, whereas quite lower rates of instable hips in newborns were reported from several other European parts. Mau indicated the limited value of clinical examinations particularly when evaluating data in a multicenter study was concerned. In our study each examiner had a statistically significant variation of his results which we found by establishing an examiners ratio (Formula: see text). Since October 1984 the clinical routine newborn screening was completed by an obligatory hip sonography in the first days of life. The sonographic examination and classification was done according to Graf's method. Real-time ultrasound machines with linear 5 MHZ-transducer were used. 8.221 newborns were examined between X/1984 and XII/1988. 72.51 percent were type Ia, b. 25.63% were categorized as type IIa; 1.66 percent were classified type IIc, D; 0.16 percent were type IIIa hips. Only one hip was classified as type IV, this was a teratological dislocated hip. 1.31 percent of all hips showed a pathologic sonogram (= type IIc, D, IIIa) without having shown abnormalities, when clinically examined a few days before. In our opinion these results emphasize the value of a sonographic newborn screening. The majority of hips with distinct abnormalities only (= lax hips, limited abduction) was type Ia, b, or IIa, whereas the majority of clinical instable hips had pathologic sonograms (= IIc, D, IIIa). Newborns delivered by breech presentation had a significant higher percentage of clinically abnormal hips (= 7.48 subluxatable and luxatable hips). The percentage of pathologic sonograms (8.81%) and type IIa hips (= 42.78%) was significantly higher compared to the normal delivered group. 336 premature newborns were found to have a statistically significant higher percentage of type Ia, b-hips (= 82.73%) and a statistically equal percentage of sonographically pathologic hips (= 0.89%) in comparison to the mature newborns.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2188433 TI - Desmopressin acetate in postoperative bleeding. PMID- 2188434 TI - Guar gum in hyperlipidemia. PMID- 2188435 TI - Thalidomide in erythema nodosum leprosum. PMID- 2188436 TI - Potentiation of pain relief with hydroxyzine: a therapeutic myth? AB - Opioid analgesics are among the oldest known medications. In spite of long usage, clinical success in controlling pain in many settings appears to be limited by a lack of understanding of the clinical pharmacology of these agents. Efforts to achieve better outcomes often focus on the use of adjunctive agents, such as hydroxyzine, in an attempt to control postoperative pain with a minimum of toxicity. Although such combined therapies are exceedingly common, clinical data supporting a hypothesis of an "opioid-sparing" effect of hydroxyzine are marked by serious methodologic flaws, including lack of placebo control, lack of statistical analyses, and use of subjective assessments, all of which compromise the validity of such conclusions. In doses that may contribute to pain relief, hydroxyzine demonstrates a significant potential for causing respiratory depression which is additive to that of opioids, but not reversible with naloxone. In total, the data do not confirm the purported clinical benefits of hydroxyzine-opioid combinations in comparison with appropriate regimens of opioids alone. PMID- 2188437 TI - Cefixime. AB - Cefixime is a new orally active third-generation cephalosporin with a broad spectrum of activity against a variety of both gram-positive and -negative bacteria including many beta-lactamase-producing strains of streptococci, Haemophilus influenzae, Neisseria gonorrhoeae, and the majority of the Enterobacteriaceae. Activity of cefixime against Staphylococcus aureus, enterococci, Listeria monocytogenes, and Pseudomonas spp. is poor. The relatively long elimination half-life of cefixime (approximately 3.0 h) has made possible once- to twice-daily administration with the potential added benefit of improved patient compliance. Clinical trials indicate that cefixime is at least as effective as standard agents in the treatment of genitourinary and upper respiratory tract infections. The incidence of resistant organisms reported during clinical trials with cefixime was low. Adverse reactions observed during clinical trials were relatively uncommon and generally mild and transient in nature. The most significant adverse reactions reported were diarrhea and stool changes occurring in up to 20 percent of patients. PMID- 2188438 TI - Angiotensin-converting enzyme inhibitors and renal function. AB - The effects of angiotensin-converting enzyme (ACE) inhibitors on renal hemodynamics vary widely depending on the preexisting physiologic and pathologic state of the kidneys. Although some studies of ACE inhibitors in primary essential hypertension have demonstrated increases in glomerular filtration rate (GFR) and effective renal plasma flow in patients with renal impairment, other studies have not shown these same beneficial results. The difference may involve the choice of ACE inhibitor used in the investigations, but controlled comparison trials are needed to determine whether this is the case. The use of ACE inhibitors in renovascular hypertension remains controversial. ACE inhibition can interfere with the autoregulation of GFR mediated by angiotensin II and may lead to deterioration of renal function, especially in patients with bilateral renal artery stenosis or stenosis of a solitary kidney. Additionally, ACE inhibitors have been shown to cause a decline in GFR in the kidney affected by the stenosis, whether or not clinically apparent renal insufficiency occurs. Although the functional impairment associated with ACE inhibitors in renal artery stenosis has generally been reversible following removal of the drug, the consequences of a long-term reduction in GFR are unknown. Treatment of stable congestive heart failure (CHF) with ACE inhibitors can result in enhancement of GFR and reduction of sodium and fluid retention, thus improving the clinical state. However, in patients with decompensated cardiac failure, renal perfusion pressures may already be at or near the autoregulatory breakpoint and ACE inhibition may cause deterioration of renal function. In general, ACE inhibitors can be used safely in CHF if they are initiated cautiously, with adjustment of ACE inhibitor and diuretic dosages to avoid systemic hypotension and sodium and fluid depletion. In studies comparing the agents, enalapril and lisinopril have both been shown to cause higher incidences of renal function deterioration than has captopril. These findings suggest that the more complete or sustained ACE inhibition seen with the longer-acting agents may be detrimental to renal function in patients with CHF. The use of ACE inhibitors in the treatment of proteinuria is the newest area of research with these agents. At present it appears that ACE inhibitors reduce urinary protein excretion the most effectively in diabetic patients with mild proteinuria and in hypertensive patients with renal insufficiency and proteinuria due to glomerular disorders. More study is needed to determine whether these agents can reduce the rate of renal failure progression and to define the patient populations expected to benefit most.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2188440 TI - A model of methods for influencing prescribing: Part II. A review of educational methods, theories of human inference, and delineation of the model. AB - The purpose of this literature review is to develop a model of methods used to influence prescribing. This article reviews well-controlled studies of educational efforts, describes and relates theories of human inference to these studies, and delineates a model of methods for influencing prescribing. The model can be used to help explain the success or failure of various programs and as a framework for developing and testing methods to influence prescribing. PMID- 2188439 TI - Angiotensin-converting enzyme inhibitors: a comparative review. AB - The chemistry, pharmacology, pharmacokinetics, adverse effects, and dosages of the three currently available angiotensin-converting enzyme (ACE) inhibitors are reviewed. This class of agents effectively inhibits the conversion of angiotensin I to the active vasoconstrictor angiotensin II, a hormone that also promotes, via aldosterone stimulation, increased sodium and water retention. The ACE inhibitors, therefore, are capable of lowering blood pressure primarily by promoting vasodilatation and reducing intravascular fluid volume. Captopril, the first orally active, commercially available ACE inhibitor, is a sulfhydryl containing compound. Captopril was followed by the introduction of enalapril and lisinopril, two non-sulfhydryl ACE inhibitors. The pharmacokinetic profiles of these three ACE inhibitors differ. Captopril has rapid onset with relatively short duration of action, whereas enalapril and lisinopril have slower onset and relatively long duration of action. Captopril is an active ACE inhibitor in its orally absorbable parent form. In contrast, enalapril must be deesterified in the liver to the metabolite enalaprilat in order to inhibit the converting enzyme; this accounts for its delayed onset of action. Lisinopril does not require metabolic activation to be effective; however, a slow and incomplete absorption pattern explains the delay in onset of activity. Captopril and its disulfide metabolites are primarily excreted in the urine with minor elimination in the feces. Approximately two-thirds of an administered enalapril dose is excreted in the urine as both the parent drug and the metabolite enalaprilat; the remainder of these two substances are excreted in the feces. Lisinopril does not undergo measurable metabolism and approximately one-third is excreted unchanged in the urine with the remaining parent drug being excreted in the feces. The ACE inhibitors lower systemic vascular resistance with a resultant decrease in blood pressure. Their efficacy is comparable to diuretics and beta-blockers in treating patients with mild, moderate, or severe essential and renovascular hypertension. In those patients with severe congestive heart failure (CHF) the ACE inhibitors produce a reduction in systemic vascular resistance, blood pressure, pulmonary capillary wedge pressure, and pulmonary artery pressure. These drugs may produce improvement in cardiac output and stroke volume and, with chronic administration, may promote regression of left ventricular hypertrophy. The antihypertensive effects of the ACE inhibitors are enhanced when these agents are combined with a diuretic. Captopril and enalapril have been shown to be of particular benefits as adjunctive therapy in patients with congestive heart failure, both in terms of subjective improvement of patient symptoms, and in improving overall hemodynamic status.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2188441 TI - Captopril-associated aplastic anemia. PMID- 2188442 TI - [Expert assessment of patients with cardiac arrhythmia]. PMID- 2188443 TI - [A health-promoting life style--a goal of the physician Dr. Friedrich Wolf]. PMID- 2188444 TI - [Albert Schweitzer--a life for humanity]. PMID- 2188445 TI - [Spices and the stomach]. PMID- 2188446 TI - [Paraneoplastic syndromes in neurology]. PMID- 2188447 TI - [Listeriosis in children]. PMID- 2188448 TI - [Non-traumatic fatalities in sports activity]. PMID- 2188449 TI - [Stomach tolerance of buffered and unbuffered low-dose acetylsalicylic acid: an endoscopy controlled double-blind study in volunteers]. AB - In this randomised double-blind cross-over study the gastroduodenal tolerability of buffered acetylsalicylic acid (ASS) (Aspalox = 325 mg ASS plus 300 mg magnesium aluminium hydroxide) daily has been compared with unbuffered ASS (325 mg) daily in 12 healthy volunteers using upper Gl-endoscopy. The treatment period lasted 14 days: endoscopic controls were performed at entry and repeated at day 14. At day 0 the mean endoscopic score averaged 0.8 +/- 0.1 in both groups (MW +/ SEM). One tablet Aspalox daily induced marked gastroduodenal damage at day 14 (6.5 +/- 1.5). The median lesion score rose from 1.0 (day 0) to 7.0 at day 14. Unbuffered ASS evoked almost identical gastroduodenal injuries at day 14 (7.5 +/- 1.8). The corresponding median values were 1.0 (day 0) and 7.0 at day 14. Our data suggest, that the amount of buffering in the Aspalox preparation is not sufficient enough to protect human gastroduodenal mucosa against low dose acetylsalicylic acid. PMID- 2188450 TI - [Diabetes and pregnancy]. AB - In recent years, new findings in the pathophysiology and treatment of diabetes mellitus during pregnancy and the development of improved fetal monitoring methods have considerably reduced the risk for mother and child. Given good metabolism the fertility of diabetics is comparable to that of nondiabetics. Perinatal mortality in centers is below 2%, and in 40% of the cases it is caused by congenital malformations. The incidence of malformations is 4-8%. Regulation of metabolism to near-normal values is vital for further improvement of mortality and morbidity rates, and should be aimed for prior to conception. In many cases insufficient attention is given to gestational diabetes. The risks accompanying untreated gestational diabetes are underestimated. In approx. 15% of such patients insulin therapy during pregnancy is necessary in addition to dietary measures. The goal of near normal metabolism (60-120 mg/dl, with mean daily values around 85-90 mg/dl) can usually be achieved during training, either prior to conception or at the latest during early pregnancy, by improved substitutional insulin therapy or insulin pump therapy. Short-term combined internalistic obstetric follow-up at 14-day intervals ensures early prevention and detection of complications. The pregnancy can be continued to term in over 80% of cases, and spontaneous birth aimed for as the primary goal in the majority. With careful monitoring of metabolism, diabetics with no vascular complications may take low dosage ovulation inhibitors to prevent conception. In isolated cases termination may be indicated in patients with severe vascular complications (proliferative retinopathy, severe nephropathy). PMID- 2188451 TI - [Use of a stapler instrument for hysterotomy in cesarean section]. AB - In a prospective, randomized study covering 100 patients with cesarean delivery the potential benefit of using a stapler for hysterotomy was investigated. Expectations were high, in particular in regard to loss of blood. However, no significant differences were found as regards this criterion, nor in the postoperative complication rate, duration of hospitalization or surgery, or febrile morbidity. The stapler is unwieldy and not always completely safe. If the higher cost of using the stapler is also taken into account one is bound to conclude that there is no reason to abandon the technique used hitherto. PMID- 2188452 TI - [Clinical aspects of lymphedema and contrast medium lymphography]. AB - Primary lymphedema of the lower extremities is a clinical entity often misdiagnosed, especially in its mild, distal forms. Its characteristics are: swelling, tightness of the skin, and deepening of the skin folds of one foot, mainly in young girls. Proximal forms with involvement of the lower leg and thigh are often congenital. In later years, these manifestations have to be distinguished from secondary lymphedema due to a block in the lymph nodes (e.g. in malignoma), starting with swelling of the proximal regions of the extremities and the genitalia. Indirect lymphography, especially with new contrast media, however, offer new diagnostic possibilities. The best routine method to confirm or exclude lymphedema is isotopic lymphography. PMID- 2188453 TI - [Cytologic methods in dermatology]. AB - Cytology is a simple, fast, and inexpensive procedure yielding a high degree of diagnostic accuracy-provided the examiner has a good deal of experience. It has not yet become generally accepted in the diagnosis of skin diseases, since biopsies are very easy to perform, and histopathology is still more reliable than cytology. Modern techniques such as electron microscopy, immunofluorescence, immunocytochemistry with polyclonal and monoclonal antibodies, immunoelectron microscopy, DNA flow cytometry, and in situ hybridization have considerably increased the potentials of cytology and will certainly help to win general recognition in dermatology, as well. PMID- 2188454 TI - [Covering circular skin defects using 4 rhombic transposition flaps]. AB - Based on Limberg's principles concerning the design of local flaps, S. B. Jugo developed a new technique for the closure of circular skin defects: The defect is divided into 4 quadrants; then 4 symmetrical rhombic flaps are raised from the surrounding skin, all pointing in the same direction of rotation. The sides of each flap correspond to the radius of the skin defect and form an angle of 68 degrees. Finally, the flaps are rotated into the defect and sutured to each other. This technique is especially useful with large lesions of the trunk. PMID- 2188455 TI - [Insulin treatment. When, where and how should insulin be given?]. PMID- 2188456 TI - [Practical aids in diabetes control]. PMID- 2188457 TI - [Doppler sonography measurement of jugular vein blood flow]. AB - By multiplying mean cross section determined with a linear array scanner by time averaged mean spatial velocity measured with a single gated pw Doppler device, internal jugular venous volume flow was computed in 50 healthy male and 50 female volunteers aged 21 to 70 years with even age distribution within this range. Right plus left flow was 793 +/- 276 ml/min in males and 799 +/- 288 ml/min in females. There was no correlation between flow and age. PMID- 2188458 TI - [Diagnosis of secondary popliteal and femoral venous insufficiency in truncal varicose veins]. AB - Serious truncular varicosis causes, after a long period of time, changes in the deep veins known as secondary popliteal- and femoral vein incompetence. The ascending pressphlebography is the common diagnostic method. The continuous-wave sonography showing a sensitivity of 3% while being 100% specific is therefore not a suitable diagnostic method. The duplex-sonography proves to be the optimal screening method with a sensitivity of 100% while being 87% specific. PMID- 2188459 TI - Cutaneous reactive hyperemia in short-term and long-term type I diabetes- continuous monitoring by a combined laser Doppler and transcutaneous oxygen probe. AB - Using a recently designed combined laser Doppler/transcutaneous oxygen probe postocclusive reactive hyperemia response was investigated in 10 healthy subjects and 33 patients with type I diabetes mellitus. From the foot dorsum sensing site simultaneous recordings of the red cell flux of the superficial skin microvasculature and cutaneous PO2 were obtained at identical measuring position and conditions. Whereas cutaneous PO2 response exhibited an uniform monophasic curve with a significantly reduced percentage increase of PO2 in short-term (p less than 0.05) and in long-term type I diabetic patients (p less than 0.001), four different laser Doppler hyperemic flux patterns were observed. Hyperemia types A and B were biphasic, type C had only a monophasic course. Apparently in type C the initial fast component of the myogenic response is missing; in type D no increase in flux or PO2 could be measured. Comparison of prevalence of these hyperemia types showed a significantly (p less than 0.05) higher prevalence of the monophasic or even absent hyperemic response in type I diabetes. The reduction in viscoelastic properties of the small arteries and arterioles in patients with type I diabetes may account for these changes which is most likely cofactor in the pathogenesis of diabetic microangiopathy. PMID- 2188460 TI - [The prognosis of the course of psoriasis]. AB - Analysis of the informative value of signs and prognostic coefficients for 35 clinical amnestic and laboratory parameters helped make up a prognostic table for the assessment of the severity of psoriasis course and therapy efficacy. After consecutive Wald's processing 28 signs were selected out of these 35. The prognostic threshold was calculated, that permitted distribution of the patients into groups with favorable and unfavorable course of psoriasis. PMID- 2188461 TI - [Immunomorphological changes in lichen ruber planus of the oral mucosa]. AB - Immunomorphologic examinations of 23 biopsy specimens of the buccal mucosa of patients with lichen ruber planus have revealed changes that confirm the hypothesis on the autoimmune nature of this disease. The basic cause of clinical manifestation of lichen planus is disordered microcirculatory system of the buccal mucosa, resultant from deposition of the immune complexes and fibrin in the vessel walls and lumen. PMID- 2188462 TI - [Paraneoplastic bullous dermatoses]. AB - The author analyzes the clinical data and paraclinical characteristics of patients with paraneoplastic bullous dermatoses, followed up at the Research Institute of Skin and Sexually Transmitted Diseases in the town of Gorki since 1980. Clinical features of Duhring's paraneoplastic dermatoses were detected, consisting in dissemination of the process with involvement of facial skin and with essential itching. Paraclinical characteristics are as follows: neither eosinophils, nor acantholytic cells are detectable in the vesicular contents, Jadassohn's test is negative, histomorphologic examination shows intraepidermal localization of the vesicle. In paraneoplastic pemphigus involvement of the mucosae alone was recorded, and the painful syndrome whose severity did not correlate with the depth of the pathologic foci; corticosteroid therapy has proved ineffective. The author recommends thorough examinations of patients with bullous dermatoses if they present with the aforesaid clinical and paraclinical characteristics. PMID- 2188463 TI - Antigenic parvovirus B19 coat proteins VP1 and VP2 produced in large quantities in a baculovirus expression system. AB - Two baculovirus expression vectors derived from Autographica californica nuclear polyhedrosis virus (AcNPV) were prepared containing the complete 2.5 kb coding region for parvovirus B19 coat protein VP1 (AcB19VP1L) and the 1.8 kb coding region for VP2 (AcB19VP2L), placed under the control of the polyhedrin promoter. The recombinant viruses were used to infect Spodoptera frugiperda cells and the proteins expressed were analysed using appropriate antibodies. AcB19VP1L-infected cells produced B19 VP1 as shown by its reaction with 13 human sera containing B19 specific antibodies in Western blot analysis and indirect immunofluorescence. The signal seen with VP1 in immunofluorescence makes it suitable for the development of a diagnostic assay based on this technique. VP1 also reacted with two monoclonal antibodies (mAbs) specific for the B19 protein part of a 196 kDa beta galactosidase B19 fusion protein expressed in E. coli. Cells infected with AcB19VP2L produced B19 VP2 which reacted with the same human sera in indirect immunofluorescence and with five of the 13 sera in Western blots. VP2 did not react with the fusion protein-specific mAbs. The large amounts of viral antigen produced in this system means the development of widely available diagnostic tests for B19 infection and the further characterization of the B19 structural proteins are within reach. PMID- 2188464 TI - A host range mutant of Newcastle disease virus with an altered cleavage site for proteolytic activation of the F protein. AB - The primary structure of the F protein of a host range mutant of the Ulster strain of Newcastle Disease virus (NDV) has been determined by nucleotide sequence analysis and compared to that of the wild type and other NDV strains. The cleavage site of the mutant had the sequence Gly-Lys-Gln-Arg-Arg as compared to two isolated basic amino acids [Gly-Lys(Arg)-Gln-Gly-Arg] with the apathogenic strains and two pairs of basic amino acids [Arg-Arg-Gln-Lys(Arg)-Arg] with the pathogenic strains. The data indicate that the cleavability of the F protein of NDV increases with the number of arginine and lysine residues at the cleavage site and that the susceptibility of the pathogenic strains to ubiquitous host proteases depends on both pairs of basic amino acids. PMID- 2188465 TI - [The morphology of microcolonies as a criterion for recognizing bacteria in the differentiation of Streptococcus pyogenes and Streptococcus group B]. AB - The authors studied the diagnostic importance of the morphology of microcolonies of S. pyogenes and group B streptococci in comparison with the currently used tests for the differentiation of these two species: the bacitracin test, the hydrolysis of sodium hippurate and the CAMP test. The standard tests proved to be positive in 94-97% and microcolonies had typical morphology in 86-95.7%. The statistical indices of the diagnostic effectiveness of differential tests varied within 93.8-98.9%. The diagnostic value of the study of the morphology of colonies was characterized by the following data: the sensitivity and prognostic negative value of the study were 95% for S. pyogenes and 86-89% for group B streptococci, while its specificity and prognostic positive value were 100% due to the absence of false positive results. PMID- 2188466 TI - [The conjugational transfer of plasmids to Legionella strains]. AB - In experiments on conjugation the transfer of a number of R-plasmids having a wide range of hosts, such as plasmids RP1, R68.45, RP4, N3, RK2, S-a, those having a narrow range of hosts, such as plasmid R64, to strains of different Legionella species was shown. The frequency of transfer varied from 3.1 X 10(-3) to 9.4 X 10(-7). The fact that the conjugation transfer was confirmed by the reverse transfer of plasmids from Legionella transconjugates to Escherichia coli strain K12, as well as by the detection of the DNA of the transferred plasmid by means of electrophoresis in agar gel. Plasmid RP1 showed different behavior in transconjugates of various Legionella species after several passages in a medium free of antibiotics. In the Legionella strain under study the unstable preservation of plasmid R64 was observed. PMID- 2188467 TI - [The genetic regulation of the virulence of bacteria in the genus Salmonella]. PMID- 2188468 TI - [The persistence and biodegradation of the cell walls of Streptococcus group A in light of the immunopathogenesis of nonsuppurative poststreptococcal diseases]. PMID- 2188469 TI - [The interaction of Rickettsia with eukaryotic cells]. PMID- 2188470 TI - [Debatable and unresolved questions in the epidemiology, pathogenesis, clinical picture, classification and nomenclature of leptospirosis]. PMID- 2188471 TI - Papillary cystic neoplasm of the pancreas. Report of a case diagnosed by fine needle aspiration cytology. AB - Fine needle aspiration (FNA) performed on a young woman who presented with a mass in the left hypochondrium yielded fluid. Smears and Cytospin preparations of the fluid showed good cellularity, consisting of relatively monomorphic cells forming a perivascular papillary pattern. FNA cytology thus suggested a diagnosis of papillary cystic neoplasm of the pancreas. Surgical removal of the pancreatic tumor and detailed histologic study confirmed the cytologic diagnosis. PMID- 2188472 TI - Fine catheter aspiration cytology of the peritoneal cavity in the diagnosis of a metastatic tumor. Report of a case with immunocytochemical studies. AB - The potential value of a new system of fine catheter aspiration (FCA) cytology of the peritoneal cavity in the diagnosis of peritoneal malignancy is illustrated by a case report. Gelman filter preparations of an FCA sample of an abdominal mass from a patient with a history of adenocarcinoma of the lung showed unequivocal malignant cells, obviating the need for further diagnostic procedures. Trial immunostaining of Cytospin preparations of part of the FCA sample showed appropriate results, suggesting that such samples may be suitable for immunoperoxidase studies to identify tumor types or to predict the source of the primary tumor in difficult cases. PMID- 2188473 TI - AANA Journal course: new technologies in anesthesia: update for nurse anesthetists--mass spectrometry in anesthesia. AB - Despite the development of mass spectrometry in the early 1900's, it has only in this decade been introduced into the clinical anesthesia arena. The mass spectrometer's ability to make simultaneous measurements of specific gases distinguish it from currently available monitoring apparatus. This article will review the basic principle of operation of the mass spectrometer. The cost of implementation of mass spectrometry, clinical applications and potential pitfalls associated with its use will also be discussed. PMID- 2188474 TI - Constant-flow ventilation during experimental left ventricular failure. AB - The efficacy of constant-flow ventilation (CFV) was investigated in dogs with normal heart function (control phase, n = 8) and after development of left ventricular failure (LVF phase, n = 8). Heated, humidified and oxygen-enriched air (inspired oxygen fraction (Fio2) = 0.4) was continuously delivered via two catheters positioned within each mainstem bronchus at two flow rates (1.2 and 1.6 l/kg/min). Conventional mechanical ventilation (CMV) with positive end-expiratory pressure (PEEP) of 0.5 kPa was used as reference ventilation. During control, neither CMV with PEEP nor CFV revealed severe impairment of cardiopulmonary performance. Alveolo-arterial PO2 difference (P(A-a)O2) increased significantly during CFV1.2 and CFV1.6, indicating a higher degree of ventilation-perfusion (VA/Q) inhomogeneity. Acute left ventricular failure (LVF) was induced by proximal occlusion of the left anterior descending (LAD) coronary artery. Cardiac output (CO), maximum velocity of pressure development (dP/dtmax) and mixed venous PO2 decreased (P less than or equal to 0.05), whereas left ventricular end diastolic pressure (LVEDP) and pulmonary capillary wedge pressure (PCWP) increased (P less than or equal to 0.05). Extravascular lung water (EVLW), as determined by thermal-dye technique, increased from 10.1 ml/kg to 20.9 ml/kg (P less than or equal to 0.01). Oxygenation, but not CO2 elimination, deteriorated in the LVF phase. There were no haemodynamic differences between CMV with PEEP and CFV1.2, but cardiopulmonary performance deteriorated with CFV1.6. Gas exchange was significantly more impaired during CFV1.2 and CFV1.6 due to increased VA/Q mismatching. However, there were no significant differences for P(A-a)O2 values between CFVControl and CFVLVF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188475 TI - The influence of body position and differential ventilation on lung dimensions and atelectasis formation in anaesthetized man. AB - The effects of body position and anaesthesia with mechanical ventilation on thoracic dimensions and atelectasis formation were studied by means of computerized tomography in 14 patients. Induction of anaesthesia in the supine position reduced the cross-sectional area for both lungs and caused atelectasis formation in dependent lung regions in 4/5 patients. Conventional ventilation with positive end-expiratory pressure (PEEP) increased thoracic dimensions and reduced, but did not eliminate, the atelectatic areas. The vertical diameters of both lungs were smaller in the lateral position as compared to the supine position (16.7 vs 10.4 cm in the left lung and 17.3 vs 12.8 cm in the right lung). The lateral positioning also caused a large reduction of the atelectatic area in the non-dependent lung. Differential ventilation with selective PEEP to the dependent lung eliminated (3/8 patients) or reduced (5/8 patients) dependent lung atelectasis. It can be concluded that lung geometry is altered in the lateral position: the shape of the lung makes the vertical diameter of each lung less in the lateral position, compared to the supine position. The atelectatic areas are mainly located in the dependent lung in the lateral position, and these atelectatic areas could be further reduced by selective PEEP to this lung. PMID- 2188477 TI - Infantile autism: diagnosis and treatment. AB - This article reviews recent developments in the diagnosis and treatment of infantile autism. Autism is currently conceptualized as a behavioural syndrome with multiple biological aetiologies. A diagnosis of infantile autism implies that a thorough neurobiological investigation is called for. The core psychological deficit necessary and sufficient to cause central autism symptoms is gradually being defined. The multiple aetiologies of autism will lead to multiple treatment in the future. At the present stage structured education and behaviour modification provide the cornerstones of any treatment programme. PMID- 2188476 TI - Effect of stannous fluoride and tetracycline on repair after delayed replantation of root-planed teeth in dogs. AB - Mandibular incisors were extracted and allowed to dry in air for 45 min. They were then root-planed extensively, leaving a cervical collar and the apical region uninstrumented, to prevent direct contact between root surface and alveolar bone after replantation while, at the same time, enabling precise and stable reseating of the tooth. Control teeth were replanted either without further treatment or after treatment with citric acid for 3 min. Experimental teeth were treated before replantation with 1% SnF2 for 5 min, 1% tetracycline HCl for 5 min, or 1% SnF2 followed by 1% tetracycline. Histometric analysis of healing in the root-planed areas showed minimal amounts of inflammatory resorption and ankylosis after 21 days in experimental teeth as compared with the control teeth. A persisting inflammatory reaction in the periodontal ligament without root resorption was, however, frequently seen. The observations confirm that the frequency of adverse healing reactions after delayed replantation of teeth from which nonvital soft tissue remnants have been removed can be reduced by demineralizing the root surface and preventing mechanical trauma to the root surface in the postoperative period. Root surface treatment with SnF2 followed by tetracycline resulted in complete absence of inflammatory resorption and ankylosis in this short-term experiment. PMID- 2188478 TI - Insulin sensitivity in patients with anorexia nervosa and bulimia. AB - Insulin sensitivity was studied using the euglycemic insulin clamp technique in 5 female patients with anorexia nervosa and 4 females with bulimia. The results were compared with those of 15 male patients with non-insulin-dependent diabetes mellitus. Euglycemic insulin clamp is performed for 2 h using the Biostator, during which time insulin was infused at a rate of 0.77 mU kg-1 min-1. Fasting plasma glucose and immunoreactive insulin tended to be lower in patients with anorexia nervosa than in those with bulimia (69.8 +/- 6.7 vs 75.9 +/- 7.7 mg/dl, and 5.9 +/- 2.0 vs 9.8 +/- 3.4 U/ml). The mean metabolic clearance rate (MCR) was 9.2 +/- 3.9 ml kg-1 min-1 for patients with anorexia nervosa, 5.1 +/- 2.2 ml kg-1 min-1 for patients with bulimia, and 3.8 +/- 0.3 ml kg-1 min-1 for patients with diabetes mellitus. However, one anorectic had a significantly high MCR. One anorectic and 3 bulimics had a significantly low MCR. These results suggest that insulin sensitivity varied in patients with anorexia nervosa, whereas it tended to decrease in some patients with bulimia but not to the same degree as in patients with diabetes mellitus. PMID- 2188480 TI - Information processing: a new model for understanding cognitive disturbances in psychiatric patients. AB - Information processing models are influenced by the information sciences and by computer technology, which progressed in the 1960s and 1970s. During the last decade these models have formed the theoretical basis for much of the experimental research on cognitive dysfunctions in psychiatric patients. An essential element in all of these models is that information is processed in several discrete stages. Different experimental paradigms have been developed in order to tap information about the processes taking place in each of these stages. Most of the research so far on pathological groups has been done on schizophrenic patients. Some deficits found in schizophrenics seem to be symptom related. This is the case with performance deficits on the Continuous Performance Test with low processing load. Other dysfunctions might be vulnerability indicators, such as deficit performance on the forced choice Span of Apprehension task and the Continuous Performance Test with high momentary processing load, backward masking, serial recall for items that involve active rehearsal, and eye movement dysfunctions. However, information processing deficits do not seem to be specifically related to schizophrenia. Deficits can be found in other psychiatric syndromes too, especially in manic patients. Generally speaking, the dysfunctions emerge in a milder form in nonschizophrenic patients. PMID- 2188479 TI - A double-blind comparison of mianserin and maprotiline in depressed medically ill elderly people. AB - A double-blind, randomized 4-week mianserin vs maprotiline trial was conducted in 48 depressed geriatric medical inpatients. The drug dosages were up to 90 mg of mianserin and up to 150 mg of maprotiline per day. Efficacy was measured by the Geriatric Depression Scale, the Hopkins Symptom Check List depression subscale and the Clinical Global Impression Scale. The overall dropout figure was 27% of the sample. Side effects were relatively similar in the two treatment groups and suggested a safety profile somewhat better than that of the first-generation antidepressants. Mianserin showed some advantages in efficacy over maprotiline, particularly by the 4th week of the trial, but the overall figures of treatment responders were rather small (Geriatric Depression Scale: mianserin 48%, maprotiline 30%). Clinical trials vs placebo are needed to clarify the role of antidepressant pharmacotherapy in depressed geriatric medical inpatients. PMID- 2188481 TI - Patterns of response during placebo treatment of panic disorder. AB - Data from the cross-national study of panic disorder are used for an analysis of response patterns. The main purpose of the study is a search for specific placebo patterns and a discussion of possible differences in patterns from patients treated with alprazolam, imipramine, and placebo. Four outcome measures were registered at baseline and weekly during the treatment period: the number of panic attacks, Physician's Global Evaluation of treatment effect, the Overall Phobia Score and the level on the Hamilton Rating Scale for Anxiety. Response patterns from the 3 treatment groups are described and compared, and subsequently categorized with regard to completeness and persistency. No specific placebo pattern is recognized. Some differences are found, however, as many placebo patients demonstrate an early and temporary remission. The variations in response patterns do not compromise the blindness of the study, and their predictive validity is low. PMID- 2188482 TI - The use of direct confrontation: the treatment-resistant schizophrenic patient. AB - Schizophrenics are often labeled treatment-resistant because the psychological treatment they receive is seldom appropriate for their needs. Specialized psychotherapy for schizophrenia is available but rarely used. Training in these methods is difficult to find. If we are to treat schizophrenia successfully, we must rethink the treatment and training process, modify our views and teach interventions that force the patient to respond to the demands of the therapist. Professionals must learn that change occurs because the therapist is stronger than the psychotic defenses of the patient, i.e., the patient's resistance to treatment. PMID- 2188483 TI - Mortality and causes of death in schizophrenic patients in Denmark. AB - A cohort consisting of 6178 people that were psychiatric inpatients with a clinical schizophrenia diagnosis in 1957 were followed up from 1957 through 1986, and their cause-specific mortality was determined. Mortality from cardiovascular diseases, lung diseases, gastrointestinal and urogenital disorders, accidents and suicide was increased, whereas mortality from cerebrovascular disorders was reduced. In the male patients cancer mortality was reduced whereas cancer mortality in the female patients was increased. Mortality from a number of causes that theoretically could be associated with side effects from neuroleptics was increased. Mortality from some causes of death used as a measurement of the quality of medical care was found to be slightly increased. Further studies of the quality of the medical care provided to schizophrenic patients and of the association between neuroleptic medication and mortality are needed. PMID- 2188484 TI - Treatment for psychoactive substance use disorder in special populations: issues in strategic planning. AB - During their recovery, special populations of alcoholics and addicts have need for both (1) involvement with their own special social identity groups and (2) involvement with others broadly representative of the communities in which they will live and function. Self-help groups and treatment institutions in the societal mainstream have often neglected special populations and their special needs. Family education, support and therapy is especially important to many patients from these special populations. Obstacles to treatment for these special groups are described, along with strategies for overcoming these obstacles. PMID- 2188485 TI - Patient characteristics and outcome of inpatient treatment for alcoholism. AB - This article reviews the literature on relationships between patient characteristics and outcome of inpatient treatment for alcoholism. The article is organized according to categories of patient variables which have been studied. These include psychological characteristics, demographic variables, degree of alcohol dependence, motivation for treatment, coping styles, and beliefs about abstinence from alcohol. Conclusions based on the studies reviewed are presented, along with a discussion of why definitive conclusions are rare in the field of alcoholism treatment research. Conceptual and methodological issues in this research area are highlighted in attempting to come to some coherent and integrated conclusions regarding the current state of knowledge, and directions for current and future research are discussed. PMID- 2188486 TI - Nutritional assessment of the hospitalized patient. PMID- 2188487 TI - Nutritional modulation of oxygen radical pathology. PMID- 2188488 TI - The role of nutrition in the prevention and treatment of hypertension. PMID- 2188489 TI - Energy metabolism of the newborn infant. PMID- 2188490 TI - [Adrenal hemangioma: a case report]. AB - We report a rare case of adrenal hemangioma incidentally discovered by computed tomography (CT) in a 75-year-old female, the hormonal examination showed within the normal range, and ultrasound-sonography, CT scan and angiography disclosed the mass to be a non-functioning adrenal tumor. The tumor was removed operatively and the pathological finding was adrenal hemangioma. Twenty reported cases found in the Japanese literature are reviewed. PMID- 2188491 TI - [A case report of emphysematous pyelonephritis]. AB - A 51-year-old male patient with diabetes mellitus consulted his home doctor because of high fever and right flank pain. Urinalysis showed marked pyuria. Treatment with antibiotics was not completely effective, and he was referred to our hospital for further examination and treatment. CT scan showed an abnormal gas shadow in right renal parenchyma. He was diagnosed with emphysematous pyelonephritis and right subcapsular nephrectomy was done after the control of diabetes mellitus. We reviewed 57 cases of emphysematous pyelonephritis including our case in the Japanese literature, and we discussed about its etiology, symptomatology, choice of treatment and prognosis. PMID- 2188492 TI - Propranolol-induced lipid changes and their prognostic significance after a myocardial infarction: the Beta-Blocker Heart Attack Trial experience. AB - Beta blockers represent the only documented effective long-term prophylactic treatment for patients after myocardial infarction (MI). Concern continues to be expressed about the lipid-altering effects of their long-term use, especially beta blockers without intrinsic sympathomimetic activity such as propranolol. Data collected for the Beta-Blocker Heart Attack Trial, the largest long-term clinical trial of beta-blocker use in patients after MI, have been analyzed to address the following questions. To what extent does propranolol alter lipid levels at least 6 months after MI and initiation of therapy? How predictive of subsequent coronary events and mortality are lipid levels 6 months after MI? Is there any evidence that altered lipid levels attenuate any of the beneficial effect of propranolol on coronary morbidity and mortality? By the 6-month post-MI visit, propranolol was shown to raise serum triglyceride levels by about 17% (approximately equal to 35 mg/dl) and lower serum high density lipoprotein (HDL) cholesterol by about 6% (approximately equal to 3 mg/dl). There was no effect on total cholesterol or low density lipoprotein cholesterol. In other analyses, no lipid measured 6 months after the MI was strongly predictive of subsequent coronary events or mortality. For example, every 1-mg-lower HDL value was associated with only a 0.7% relative increase in the mortality rate. Theoretically, the estimated relative increase on all-cause mortality associated with propranolol-induced HDL reduction is about 2%. In multivariate analyses adjusting for changes in HDL and serum triglyceride, propranolol-induced beneficial reductions in mortality and morbidity remained on the order of 20%, 10 times the estimated hazard. PMID- 2188493 TI - Comparison of the effects of a controlled-release formulation of isosorbide-5 mononitrate and conventional isosorbide dinitrate on exercise performance in men with stable angina pectoris. AB - Thirty-three men with stable exercise-induced angina pectoris entered a randomized, double-blind, crossover study in which controlled-release isosorbide 5-mononitrate 60 mg once daily was compared with conventional isosorbide dinitrate 20 mg 3 times daily. Each drug was given for 2 weeks. Twenty-eight patients completed the study and data on exercise variables are available in 23 patients. Treatment with either drug resulted in significant antianginal effects, when measured 6 hours after a single dose and after 2 weeks of therapy compared with baseline placebo; however, there were significantly fewer signs of myocardial ischemia during treatment with isosorbide-5-mononitrate. There was no evidence of tolerance to either drug treatment but a significant attenuation of resting blood pressure (but not of exercise blood pressure) was observed with both drugs. Headache was the only clinically significant adverse event during therapy and it occurred more frequently in the isosorbide dinitrate treatment group (p less than 0.05 vs placebo); 3 such patients had to withdraw from the study because of headache. Thus, once-daily, controlled-release isosorbide-5 mononitrate appears as effective as conventional isosorbide dinitrate 3 times daily in patients with stable angina pectoris. The once-daily administration is convenient and improves patient compliance. PMID- 2188494 TI - Clinical significance of silent ischemia in unstable angina pectoris. AB - In a prospective study the significance of silent ischemia was evaluated in 66 patients with a clinical diagnosis of unstable angina (no requirement for reversible ST-T changes during pain on 12-lead electrocardiograms before entry), and the results of continuous 2-channel electrocardiographic (ECG) recordings, begun within 24 hours of admission, were compared with other clinical and ECG predictors of adverse outcome. Ischemic changes were detected in 7 patients (11%) during a mean of 41 hours of recording. There were 37 episodes of transient ST segment change (16 ST elevation, 21 ST depression) of which 11 (30%) were symptomatic and 26 (70%) were silent. All 7 patients had at least 1 silent episode and 5 also had symptomatic episodes during the recording but only 2 patients had exclusively silent episodes. During a mean follow-up of 13.3 months, 3 patients died, 5 had a nonfatal myocardial infarction and 32 required revascularization. Although transient myocardial ischemia during the continuous ECG recording, whether silent or symptomatic, was a specific predictor of subsequent nonfatal myocardial infarction or death (specificity 92%), its sensitivity for these events was low (25%). In contrast, recurrent rest pain (greater than or equal to 1 episode) occurred in all patients with these serious adverse events (sensitivity 100%, specificity 49%). Transient ischemia occurs infrequently during continuous ECG recordings in patients with unstable angina not selected by reversible ST-T changes on a 12-lead electrocardiogram at entry. Recurrent rest pain after hospital admission is a more sensitive predictor of serious events in this group. PMID- 2188495 TI - Usefulness of a systemic hypertension in-hospital educational program. AB - The effects of an educational program on compliance and blood pressure (BP) control were assessed in 47 hypertensive patients hospitalized for nonhypertension-related diseases. Patients were randomized to receive either a questionnaire and an educational program (group I, 25) or questionnaire only (group II, 22). Baseline clinical characteristics, admission diagnoses and antihypertensive medications were similar between the groups. Antihypertensive medications used by patients before the trial were not changed. Eight weeks after the initial intervention, patients in group I showed a significant reduction in both systolic and diastolic BP (137/89 vs 154/98 mm Hg, p = 0.005 and 0.006, respectively) and improved compliance (96 vs 36%, p = 0.04), compared with patients in group II. An education program in patients with high BP is an effective method to improve compliance and BP control in the short-term. PMID- 2188496 TI - Real-time intravascular ultrasound imaging in humans. AB - The capability of obtaining cross-sectional, high resolution images of arteries with the use of ultrasound catheters has recently been demonstrated in animal studies. In this study the in vivo feasibility of intravascular ultrasound imaging in humans was evaluated. In 26 patients who had undergone diagnostic cardiac catheterization or iliofemoral arteriography, 1 of 3 different models of 20-MHz ultrasound catheters was advanced retrograde, into the iliac arteries and aorta or anterograde into the femoral arteries and real-time cross-sectional images of the arteries were obtained in all. In 10, the iliac arteries were normal and appeared circular and pulsatile with a 3-layered wall and crisply defined lumens. In 7 patients with nonobstructive plaques, the plaque was easily identified in the ultrasound image as a linear, bright, adynamic echo-dense structure. In 4 with obstructive disease in the iliac artery, the arterial lumen appeared irregular, bordered by a thickened, nonpulsatile wall. Variable grades of atheromatous abnormalities in the wall could be visualized. In all 5 patients with arteriographic evidence of obstructive disease of the femoral artery, intravascular ultrasound displayed reduced lumens and irregular borders with protruding high-intensity echoes in the wall. In all patients, the arterial lumen and the normal or abnormal wall were well visualized in the ultrasound images. There were no complications. This study thus demonstrates the feasibility of intravascular ultrasound imaging of arterial circulation in humans. With further improvements in catheter design and image quality, this imaging approach is likely to have a number of potential applications in the assessment of peripheral and coronary arterial diseases and in guiding interventional therapeutic procedures. PMID- 2188497 TI - Suppression of ventricular arrhythmias by magnesium. PMID- 2188498 TI - The case of Ohio v. Robinson. An 1870 bite mark case. AB - In 1870, Ansil L. Robinson was charged with the murder of his mistress, Mary Lunsford, in Mansfield, Ohio, U.S.A. Evidence against Robinson included an attempt to match his teeth to bite marks on the victim's arm. Robinson was acquitted after a 3-week trial despite the evidence linking his teeth to the wounds. This trial represents an early and perhaps the first attempt to admit bite-mark evidence in a court of law in the United States. The acquittal resulted in the obscurity that prevented this case from coming to the awareness of the forensic dental and legal communities sooner. PMID- 2188499 TI - An assessment of error in parental occupation from the birth certificate. AB - This study used data obtained through interview with the mother to determine whether parental occupations from the California birth certificate were representative of maternal occupations during the first trimester of pregnancy or paternal occupations 3 months before conception. For 71% of mothers and 80% of fathers, the occupation on the birth certificate was the same as the occupation elicited from the interview. The sensitivity of the birth certificate for determining whether a mother or father was employed or employed in a particular standard occupational category ranged from 50 to 100%. The bias to the odds ratio associated with a sensitivity of 75% and a specificity of 80% is presented. The results suggest that the use of birth certificate information on parental occupation to screen for associations with congenital malformations will miss all but very strong associations. PMID- 2188500 TI - Smoking and cervical cancer--current status: a review. PMID- 2188501 TI - Age at onset as an indicator of familial risk of breast cancer. AB - The familial risk of breast cancer was investigated in a large population-based, case-control study conducted by the Centers for Disease Control. The data set included 4,730 histologically confirmed breast cancer cases aged 20-54 years and 4,688 controls who were frequency matched to cases by geographic region and 5 year categories of age. Family history of breast cancer among first-degree female relatives of cases and controls was utilized. To identify factors associated with familial risk of breast cancer, a Cox proportional hazards model was used, modeling time to onset of breast cancer among mothers and sisters. Case relatives were at greater risk than control relatives. Among relatives of cases, a significant increase in the risk of breast cancer was associated with decreasing age at onset of the case and with having an additional relative affected with breast cancer. The hazard ratio for the mother of a case with breast cancer diagnosed at 50 years of age was 1.7 (95% confidence interval (Cl) 1.4-2.0), compared with 2.7 (95% Cl 2.2-3.2) and 4.3 (95% Cl 3.3-5.6) for the mother of a case whose diagnosis occurred at 40 and 30 years of age, respectively. The hazard ratio for the sister of a case with an unaffected mother and at least one affected sister in addition to the case was 3.6 (95% Cl 2.1-6.1) when the case was diagnosed at age 50, compared with 5.8 (95% Cl 3.4-10.0) and 9.4 (95% Cl 5.3 16.7) when the case was diagnosed at 40 and 30 years of age, respectively. The hazard ratio for the sister of a case with an affected mother and no additional affected sisters was 5.9 (95% Cl 3.9-8.9) when the case was diagnosed at age 50, compared with 9.4 (95% Cl 6.2-14.4) and 15.1 (95% Cl 9.4-24.3) when the case was diagnosed at 40 and 30 years of age, respectively. The hazard ratio for the sister of a case with both an affected mother and at least one affected sister aside from the case was 17.1 (95% Cl 9.4-31.3) when the case was diagnosed at age 50, compared with 27.5 (95% Cl 15.0-50.3) and 44.2 (95% Cl 23.5-83.2) when the case was diagnosed at 40 and 30 years of age, respectively. No effect of case's menopausal status and bilaterality was found, indicating that in addition to a positive family history, age at onset is the strongest indicator of a possible genetic subtype of breast cancer in these data. PMID- 2188502 TI - In memoriam. Professor Luigi Parmeggiani (1918-1989). PMID- 2188503 TI - But they are not thresholds: a critical analysis of the documentation of Threshold Limit Values. AB - Threshold Limit Values (TLVs) represent conditions under which the TLV Committee of the American Conference of Governmental Industrial Hygienists (ACGIH) believes that nearly all workers may be repeatedly exposed without adverse effect. A detailed research was made of the references in the 1976 Documentation to data on "industrial experience" and "experimental human studies." The references, sorted for those including both the incidence of adverse effects and the corresponding exposure, yielded 158 paired sets of data. Upon analysis it was found that, where the exposure was at or below the TLV, only a minority of studies showed no adverse effects (11 instances) and the remainder indicated that up to 100% of those exposed had been affected (8 instances of 100%). Although, the TLVs were poorly correlated with the incidence of adverse effects, a surprisingly strong correlation was found between the TLVs and the exposures reported in the corresponding studies cited in the Documentation. Upon repeating the search of references to human experience, at or below the TLVs, listed in the more recent, 1986 edition of the Documentation, a very similar picture has emerged from the 72 sets of clear data which were found. Again, only a minority of studies showed no adverse effects and TLVs were poorly correlated with the incidence of adverse effect and well correlated with the measured exposure. Finally, a careful analysis revealed that authors' conclusions in the references (cited in the 1976 Documentation) regarding exposure-response relationships at or below the TLVs were generally found to be at odds with the conclusions of the TLV Committee. These findings suggest that those TLVs which are justified on the basis of "industrial experience" are not based purely upon health considerations. Rather, those TLVs appear to reflect the levels of exposure which were perceived at the time to be achievable in industry. Thus, ACGIH TLVs may represent guides of levels which have been achieved, but they are certainly not thresholds. PMID- 2188504 TI - Modifications of endocrine-metabolic abnormalities of uremia by continuous ambulatory peritoneal dialysis. AB - The endocrine-metabolic disturbances of renal failure have numerous underlying mechanisms. These include abnormal secretion, transport and target cell binding and impaired synthesis or elimination by the diseased kidney. Neither hemodialysis nor CAPD removes large quantities of retained hormones. By correcting certain metabolic, fluid and electrolyte abnormalities, however, dialysis may improve some endocrine disturbances. Other factors such as malnutrition, glucose loading, protein loss, trace metal accumulation and drug ingestion may influence the endocrine-metabolic aspects of renal failure treated by dialysis. Hormonal stimulation and action can be adversely affected by hyperendorphinism due to retained opioids which may be removed by dialysis [88]. Possibly due to the more permeable membrane or because of continuous therapy, peritoneal dialysis seems to have a more salutary effect on hormonal regulation of salt and water balance, of erythrocyte mass and of female reproductive function than hemodialysis does. PMID- 2188505 TI - Solvent nephrotoxicity in humans and experimental animals. AB - Evidence from human case reports, epidemiologic studies and animal experiments have suggested that exposure to organic solvents is associated with a wide spectrum of renal disorders, including tubular necrosis, interstitial disease, glomerulonephritis and neoplasia. This review summarizes what is known about solvent-induced renal damage in humans and experimental animals, with emphasis on hypothesized mechanisms by which this broad range of disorders may occur. PMID- 2188506 TI - Role of aldosterone in the sodium retention of patients with nephrotic syndrome. AB - The role of aldosterone in the abnormal sodium retention in patients with nephrotic syndrome has been debated. In fact, studies using a converting enzyme inhibitor to lower plasma aldosterone have rejected such a role. We therefore studied 5 nephrotic patients and 6 control subjects by using the more specific aldosterone antagonist, spironolactone. After withdrawal of diuretics 5 days prior to the study, the nephrotic patients and control subjects were placed on a high-sodium diet (285 +/- 6 mEq/day) for 8 days. After 4 days, spironolactone 200 mg p.o., b.i.d., was given for the remaining 4 days. Plasma renin activity and plasma aldosterone levels were similar in both nephrotic patients and control subjects before the study, after sodium loading and after spironolactone had been given. After 4 days of high sodium intake control subjects were in sodium balance, but the nephrotic patients were in a positive sodium balance (approx. 80 mEq/day; p less than 0.01). On days 3 and 4 of spironolactone, the nephrotic patients exhibited an increase in urinary sodium excretion (205 +/- 20 vs. 312 +/ 13 mEq/day; p less than 0.005) but not the control subjects (279 +/- 16 vs. 286 +/- 13 mEq/day; NS). It is therefore concluded that aldosterone is a significant contributor to the sodium retention in patients with nephrotic syndrome. PMID- 2188507 TI - Sensitivity of erythrocytes to oxidant stress in uremia. AB - The erythrocytes from 19 chronic hemodialysis patients were examined for Heinz bodies and their sensitivity to oxidant stress. Heinz bodies were found in 63% of patients and an elevated level of oxidized hemoglobin in 36%. When exposed to acetylphenhydrazine oxidant stress, 84% had a normal response and 95% had stable reduced glutathione levels. Ascorbic-acid-induced oxidant stress was tolerated by 84%. The activities of enzymes associated with the hexose monophosphate shunt were examined and found to be intact. This study demonstrates an increased number of Heinz bodies in hemodialysis patients. However, this is not due to an increased sensitivity to oxidant stress. Other mechanisms must be sought to explain the presence of Heinz bodies in these patients. PMID- 2188509 TI - Custody after divorce: demographic and attitudinal patterns. AB - In a reanalysis of data from a large sample of divorced parents, joint residential custody--and joint legal custody to a lesser extent--was shown to be a favorable arrangement for couples who chose it and for their children. Parents with joint custody reported better cooperation with former spouses and greater financial resources than did those with sole custody. No association was found between children's adjustment and form of custody. PMID- 2188508 TI - Recurrent allograft antiglomerular basement membrane glomerulonephritis in a patient with Alport's syndrome. AB - A patient with Alport's syndrome and chronic renal failure received a cadaver kidney graft. Four months after the transplantation, he developed glomerulonephritis induced by anti-glomerular basement membrane (GBM) antibody. The graft failed, and the patient returned to haemodialysis. Twenty-two months later the patient received a second cadaver kidney graft. Ten months after the second transplant, he developed a recurrent anti-GBM glomerulonephritis. This observation suggests that anti-GBM disease can recur in a second transplanted kidney in a patient with Alport's syndrome. PMID- 2188510 TI - Motives and psychodynamics of self-reported, unincarcerated rapists. AB - Fifteen men, classified by self-report as rapists and attempted rapists, but who had never been arrested or convicted, were compared to a matched control group on standardized instruments and content-coded interviews. Differences in hostility toward women, power motivations, and hypermasculinity were similar to findings from studies of convicted rapists. However, results suggest a greater role for the father in the etiology of rape-associated dynamics than has previously been reported. PMID- 2188511 TI - Cochlear otosclerosis: does bone formation affect cochlear implant surgery? AB - This study aimed to demonstrate that new bone formation in the scala tympani of patients deaf from otosclerosis does not preclude cochlear implant surgery. In seven temporal bones from patients with otosclerosis, we measured the extent of new bone from the round window to the distal part of the new growth. We compared results to surgical data on the extent of drilling and depth and ease of placement of the electrode in 20 patients deaf from otosclerosis. We also examined clinical performance and voltage requirements for long-term implant use in patients with and patients without ossification of the scala tympani. Findings in our limited sample of patients and bones show that obstruction of the basal turn, which occurs in some otosclerotic patients, does not preclude implant surgery. The dynamic range in the studied sample was relatively stable long-term and clinical performance did not differ between groups with and without an ossified scala tympani. PMID- 2188512 TI - A review of acoustic tumors: 1983-1988. AB - This is a review of the English literature relative to acoustic tumors from 1983 through 1988. In January of 1984, a similar article was published in this journal which reviewed the literature from 1979 through 1982. We have selected what we consider the most important articles from the hundreds that were published on this subject. Many other significant papers are not discussed. The material is presented in 11 categories: diagnosis, histopathology, treatment, hearing preservation, facial nerve preservation and repair, von Recklinghausen's disease and bilateral tumors, nonacoustic cerebellopontine angle tumors, instrumentation, basic research, complications of surgery, and miscellaneous topics. In each section the articles are briefly reviewed, and sometimes our personal point of view is expressed. PMID- 2188513 TI - The relation between alcohol problems and the anxiety disorders. AB - The idea that people suffering from anxiety have a proclivity to consume alcohol to relieve their symptoms is supported by reports showing high comorbidity rates of alcohol and anxiety problems. The authors reviewed relevant epidemiologic surveys, family studies, and field studies and conclude that the relationship between alcohol problems and anxiety appears to be variable among the anxiety disorders. In agoraphobia and social phobia, alcohol problems appear more likely to follow from attempts at self-medication of anxiety symptoms, but panic disorder and generalized anxiety disorder may be more likely to follow from pathological alcohol consumption. Simple phobia does not appear to be related to alcohol problems in any meaningful way. PMID- 2188514 TI - Organic mental disorders caused by HIV: update on early diagnosis and treatment. AB - HIV directly affects the CNS, primarily causing subcortical neuropathology. Dementia as the initial presentation is rare, but organic mental changes that mimic many functional disorders can occur during the course of infection. The mental status examination is not adequately sensitive to detect noncognitive dysfunction, and subjective complaints, neurological signs, reduced T4 lymphocytes, CSF abnormalities, diffuse slowing on ECG, mild cerebral atrophy on brain CT, and nonspecific hyperdensities on brain magnetic resonance imaging do not correlate reliably with early and subtle HIV-induced neuropsychological impairment. Zidovudine (AZT) can delay or reverse mental deficits, and psychostimulants can reduce apathetic withdrawal, but high-potency neuroleptics can cause neuroleptic malignant syndrome. PMID- 2188515 TI - Reminiscences: 1938 and since. AB - The author cites significant changes in the conduct of the psychiatric profession between the fourth and ninth decades of this century. Determinants of the changes included the impact of World War II, the National Mental Health Act of 1946, the evolution of multiple modes of psychotherapy, the move from a system of involuntary incarceration and treatment in public institutions to a voluntaristic and pluralistic system, the provision of public and private insurance support for office, outpatient, and inpatient psychiatric care, the resurgence of psychopharmacology, and the pursuit of research in biological and psychosocial fields. The social goals of the profession are also discussed. PMID- 2188516 TI - Buspirone augmentation of fluoxetine in obsessive-compulsive disorder. AB - Eleven obsessive-compulsive patients underwent a prospective open-label trial of fluoxetine monotherapy followed by buspirone augmentation. The combination therapy was statistically superior to fluoxetine monotherapy. The results point to the importance of the 5-HT1a receptor in obsessive-compulsive disorder. PMID- 2188517 TI - A survey of state Medicaid policies for coverage of abortion and prenatal diagnostic procedures. AB - In the summer of 1988, we surveyed all states to evaluate access to Medicaid funding for abortion after the diagnosis of an anomalous fetus. All state Medicaid programs covered amniocentesis, and most had expanded coverage to include newer prenatal diagnostic procedures for eligible women. In 29 states, however, abortion coverage was limited to instances when continuation of abortion threatens the life of the mother. Only 13 states paid for a woman on Medicaid to obtain an abortion after diagnosis of an anomalous fetus. PMID- 2188518 TI - Percutaneous and open surgical repairs of Achilles tendon ruptures. A comparative study. AB - A comparative study between percutaneous repair and open surgical repair of acute spontaneous Achilles tendon ruptures in young athletic patients is presented. Twenty-seven patients with acute Achilles ruptures were evaluated objectively and with subjective questionnaires. Fifteen of the patients were treated by reconstruction with a gastrocsoleus fascial graft (followup, 4.6 years) and 12 treated by percutaneous repair (followup, 1.8 years). Subjectively, both groups were very satisfied with the results of their treatment. Cybex II dynamometer measuring strength, power, and endurance revealed no statistical significant differences between groups, even in light of the shorter followup of the percutaneous group. The percutaneous repairs demonstrated significantly more symmetry in injured/uninjured tendon size than did the open surgical repairs. Two reruptures occurred in the percutaneous group. No other complications were noted. After evaluation of both subjective and objective data we recommend percutaneous repair in the recreational athlete and in patients concerned with cosmesis. Open repair is recommended for all high-caliber athletes who cannot afford any chance of rerupture. PMID- 2188519 TI - Staple migration simulating lateral meniscus injury. A case report. PMID- 2188520 TI - Localization of interleukin-1 in human cholesteatoma. AB - Recent studies by other investigators have shown that interleukin-1 (IL-1) promotes bone resorption by stimulating various cells. Interleukin-1 not only stimulates collagenase production by fibroblasts and macrophages, but also acts as an osteoclast-activating factor. In this study, IL-1 was localized in human cholesteatoma tissues using both immunoperoxidase and immunofluorescent-staining methods with specific monoclonal antibodies. Highly concentrated IL-1 was found in the epithelial layer and granulation tissue. More specifically, intense staining was seen in basal and spinous cells of the epithelial layer, and in fibroblasts and macrophages of the granulation layer. We also located IL-1 in the normal external ear canal skin; however, the intensity of the staining in the cholesteatoma epithelium was found to be stronger. The presence of IL-1 in the epithelial layer and granulation tissue of the cholesteatoma suggests that IL-1 from the stimulated keratinocytes of the cholesteatoma could be one factor responsible for the markedly increased bone resorption observed in cholesteatoma patients. PMID- 2188521 TI - The proceedings of the 5th International Conference on the Rett Syndrome. Vienna, November 4-7, 1988. Dedicated to Professor Andreas Rett. PMID- 2188522 TI - The Rett syndrome bibliography III, 1989. PMID- 2188523 TI - The Rett syndrome program project at Baylor College of Medicine. AB - The Baylor Rett syndrome (RS) program project has enrolled more than 60 of the anticipated 70 children to be evaluated over 5 years. The program is composed of 6 individual projects and a Core center for coordinating the evaluations and managing the data. The projects consist of I) Clinical assessment of RS; II) Status of communication skills in RS; III) Clinical neurophysiology and sleep in RS; IV) Epidemiology of RS; V) Molecular genetics in RS; and VI) Neuropathology of RS. This program project and a similar program at the Johns Hopkins University School of Medicine are complementary. PMID- 2188524 TI - Measurement of 2-deoxyglucose and 2-deoxyglucose 6-phosphate in tissues. AB - The enzymatic methods previously described for 2-deoxyglucose (DG) and 2 deoxyglucose 6-phosphate have been refined and adapted to measurements of brain samples ranging from 50 mg wet weight to less than a microgram dry weight. Procedures for preparing such samples for assay are described. Analytical properties of the enzymes employed are given together with means for overcoming their possible short comings. Emphasis is placed on information useful for employing DG to assess rapid changes in glucose metabolism. PMID- 2188525 TI - Epidural droperidol and morphine for postoperative pain. AB - Epidural morphine is effective in the treatment of postoperative pain, but the incidence of associated side effects is high. To assess a potential reduction of opioid side effects by droperidol, 4 mg morphine with either placebo or 2.5 mg droperidol was injected epidurally in a double-blind, randomized, postoperative trial. Forty patients undergoing hip replacement surgery were studied. The overall incidence of side effects during the first 24 h in the group receiving droperidol and morphine was less than 50% of that in the group receiving placebo and morphine (P less than 0.008). Pruritus, emesis, nausea, urinary retention, and hypotension were diminished in the group with droperidol. No significant differences in duration or quality of analgesia were seen. Epidural injection of droperidol did not result in any local or systemic side effects. PMID- 2188526 TI - Comparison of halothane, isoflurane, alfentanil, and ketamine in experimental septic shock. AB - The effects of four commonly used anesthetic agents, halothane, isoflurane, alfentanil, and ketamine, on cardiovascular function and oxygen balance were studied in a dog model of septic shock. After initial pentobarbital administration, the dogs were given Escherichia coli endotoxin (3 mg/kg) and, after 30 min, fluids to restore cardiac filling pressures to baseline levels. This resulted in a low resistance shock in all animals. Dogs were then given for 2 h either halothane (n = 9, 0.5 MAC), isoflurane (n = 9, 0.5 MAC), or alfentanil (n = 9, 150 micrograms/kg IV plus 2 micrograms.kg-1.min-1) or ketamine (n = 9, 2 mg/kg IV plus 0.2 mg.kg-1.min-1) or no anesthetic (control: n = 9). Mean arterial pressure increased in the control group (+11 +/- 18 mm Hg) and with ketamine (+10 +/- 20 mm Hg), remained unchanged with isoflurane (-2 +/- 11 mm Hg), and decreased with halothane (-22 +/- 23 mm Hg) and alfentanil (-9 +/- 23 mm Hg). Heart rate tended to increase in the control group but decreased with the four anesthetic agents, especially with alfentanil and halothane. Cardiac index and left ventricular stroke work index increased in the control group and in each anesthetic group except the halothane group. Systemic vascular resistance decreased in all groups except in the ketamine group. In the control group, the increase in cardiac index was associated with significant increases in oxygen delivery and consumption, and with a significant decrease in blood lactate levels. There was a dramatic decrease in oxygen consumption in all anesthetic groups, whereas oxygen delivery failed to increase only with halothane. Blood lactate increased significantly with halothane (5.0 +/- 1.5 to 6.3 +/- 1.4 mM/L) and isoflurane (4.8 +/- 1.1 to 5.3 +/- 1.2 mM/L), remained unchanged with alfentanil (4.5 +/- 1.5 and 4.6 +/- 0.8 mM/L), and tended to decrease with ketamine (4.9 +/- 1.4 to 4.5 +/- 1.4 mM/L). In conclusion, among the four anesthetic agents tested, halothane had the least desirable effects. Ketamine best preserved cardiovascular function and appeared to have the least deleterious effects on the hypoxic tissues. Thus, ketamine could be the anesthetic agent of choice in septic shock. PMID- 2188527 TI - Venous embolism during cesarean section. PMID- 2188528 TI - PEEP valve barotrauma. PMID- 2188529 TI - Portrait of a giant. PMID- 2188530 TI - [Study of albumin conformational changes in human serum using an immunoenzymatic technic using monoclonal antibodies]. AB - The specificity of six peroxidase-labelled anti-albumin monoclonal antibodies was studied by allowing them to react with albumin-derived fragments of known structure comprising the whole albumin molecule. The epitopes corresponding to these antibodies were located on defined regions of the albumin molecule extending from the N to the C-terminal ends. These antibodies have been used for investigating by ELISA the conformational alterations of albumin molecule brought about by the N-B transition in twelve individual sera. The results do not show any significant differences between the sera. The N-B transition involves essentially the N-terminal portion of the albumin molecule. There also exists as modification of the C-terminal region which is however much less pronounced than the one in the N-terminal region. In addition, it is not observed when using isolated albumin. PMID- 2188531 TI - [Comparison of two systems for identifying coliform enterobacteria newly described or rarely found in clinical practice]. AB - The API 20 EC and ATB 32 GN identification systems were compared for their ability to identify 231 coliform bacteria strains. Agreement with the identification given by conventional methods was achieved for 96.1 p. cent of strains by the API 20 EC gallery and for 95.9 p. cent by the ATB 32 GN system. Complementary tests were needed to identify 9.5 p. cent of strains using the API 20 EC system but 30.3 per cent using the ATB 32 GN system. PMID- 2188532 TI - [Hepatic triglyceride lipase]. AB - The post-heparin plasma contains two lipolytic enzymes. This review deals with the lesser known, hepatic triglyceride lipase. Like lipoprotein lipase, H-TGL is a glycoprotein and has an optimal pH of 8-9. But it does not require an activator protein and its activity is not inhibited by NaCl or protamine sulfate. Synthesized by the hepatocytes, H-TGL is located at the hepatic vascular endothelium. It catalyses the hydrolysis of a wide variety of lipid substrates including triacylglycerol and phospholipids. The function of the enzyme is still not fully known. H-TGL may function in the clearance of triglyceride rich lipoprotein remnants and in the catabolism of HDL. PMID- 2188533 TI - [Serum amyloid A apolipoprotein (apo SAA). Implications in inflammation and in lipoprotein modifications]. AB - The measurement of serum amyloid A apolipoprotein (apo SAA) during acute phase inflammation offers a high interest because of its specificity, sensitivity and early increase of its levels, compared to other acute phase proteins. Furthermore apo SAA is transported in serum in association with lipoproteins, in particular with their denser subpopulation, HDL3 thus inducing their modification. The decrease in Lp AI:AII concentrations in inflammatory diseases is the consequence of the decrease in HDL3. In general the HDL3 composition was changed with a displacement of apo AI by SAA. Another interest to this protein is its relationship with amyloidosis. Apo SAA is the presumed precursor of amyloid A protein, which can be deposited in various tissues, leading to secondary amyloidosis. PMID- 2188534 TI - Experiences with a new assay for pancreas specific alpha-amylase. AB - The evaluation of an enzymatic colorimetric method to measure pancreas amylase activity in serum using two monoclonal antibodies that specifically inhibit salivary amylase is described. The assay is quick, easy to perform and can be automated easily. Within-run and day-to-day precision studies gave CVs of less than or equal to 1.5 p. cent and less than or equal to 2.6 p. cent respectively. The test is linear up to 2,150 U/L. Salivary amylase activities up to 20,000 U/L did not contribute more than 2 p. cent to pancreatic amylase activity present in a serum sample. A significant interference by bilirubin is found. Reference values were established for both pancreatic and total amylase activities in serum and used for interpreting the results of pancreatic amylase and total amylase in 72 randomly selected patients. Results obtained by this method agree well with a lectin inhibition method (r = 0.9886). PMID- 2188535 TI - ["Diabetic rosettes": a cellular immunity marker in subjects at risk for type I diabetes]. AB - The authors have previously described a marker of cell-mediated, called "diabetic rosettes", revealed by the increased binding of CD3 CD4 lymphocytes from type I diabetic patients to beta-cell membrane antigens, as compared to lymphocytes from control subjects. In the present study, they have detected such "diabetic rosettes" in some subjects at risk for type I diabetes. The mean value of lymphocytes adhering to beta (RINm5F)-cells (beta-CL) was statistically higher in those subjects at risk than in control blood bank donors (p = 0.003). When a positive test was arbitrarily defined as a value of beta-CL higher than the 95th percentile of controls, 20 p. cent of the subjects at risk were classified as beta-CL+. No difference was observed between two subgroups of subjects at risk: first degree relatives of type I diabetic patients, and non-diabetic subjects with transient hyperglycaemia. "Diabetic rosettes" were associated with HLA DR 3/4 heterozygosity (p less than 0.04) and with a "low" acute insulin release to IV glucose (p = 0.05). They were not associated with islet-cell antibodies, insulin autoantibodies, or "activated" (HLA DR+) T-lymphocytes. The authors suggest that "diabetic rosettes" represent a marker of cellular immunity in some subjects at risk for type I diabetes. PMID- 2188536 TI - Contribution of sorbitol combined with activated charcoal in prevention of salicylate absorption. AB - The use of cathartics and activated charcoal in treating toxic ingestions has become a standard treatment modality. Sorbitol has been shown to be the most rapidly acting cathartic, but its therapeutic significance has been debated. Using a previously described aspirin overdose model, ten healthy volunteers participated in a crossover design study that investigated the effect of activated charcoal alone versus that of activated charcoal and sorbitol in preventing salicylate absorption. In phase 1 of the study, subjects consumed 2.5 g aspirin followed by 25 g activated charcoal one hour later. Urine was collected for 48 hours and analyzed for quantitative salicylate metabolites. Phase 2 was identical except that 1.5 g/kg sorbitol was consumed with the activated charcoal. The mean amount of aspirin absorbed without the use of sorbitol was 1.26 +/- 0.15 g, whereas the mean absorption was 0.912 +/- 0.18 g with the addition of sorbitol. This is a 28% decrease in absorption of salicylates attributable to the use of sorbitol. The difference is significant at P less than .05 by the paired Student's t test. This study demonstrates that the addition of sorbitol significantly decreases drug absorption in a simulated drug overdose model. Effects on absorption in actual overdose situations and on patient outcome should be the subjects of further study. PMID- 2188537 TI - A prospective, population-based study of acute ibuprofen overdose: complications are rare and routine serum levels not warranted. AB - The availability of ibuprofen without a prescription requires assessment of its acute toxicity in the general population. We report results from a prospective study of 329 cases of ibuprofen overdose from a statewide cohort that were reported to our poison center between April 1985 and November 1986; 85 patients had ibuprofen serum concentrations measured. Gastrointestinal disturbances and central nervous system depression were the most common clinical findings (42% and 30% of patients, respectively), but the severity was mild; only one patient had severe symptoms that could be attributed to ibuprofen. Ibuprofen serum concentrations correlated poorly with gastrointestinal symptoms (r = -.177), central nervous system findings (r = .176), presence of coingestants (r = .078), and presence of potentially life-threatening symptoms (r = .087). We evaluated the usefulness of a previously published nomogram to predict ibuprofen toxicity; the positive predictive value for severe symptoms was 6% for all patients and 0% for patients ingesting ibuprofen alone. We conclude that the frequency of life threatening complications from ibuprofen overdose is low, the nomogram is not predictive of toxicity, and routine serum concentration determinations are not useful as an adjunct in the management of overdose cases. PMID- 2188539 TI - Clinical toxicology fellowships. PMID- 2188538 TI - 50% dextrose: antidote or toxin? AB - The empiric administration of 50% dextrose to all patients presenting to the ED with altered mental status is a standard of care predicated on the assumption that glucose administration is harmless to non-hypoglycemic patients. Considerable evidence now disputes this assumption. Glucose administration before complete cerebral ischemia in experimental animals worsens neurologic and histologic outcome. Administration of glucose during severe incomplete ischemia has a similar detrimental effect. The translation of these experimental findings into clinical practice has been slow, perhaps hindered by the frequent use of rodent models and large bolus doses of glucose. However, evidence is now provided by primate and human studies and by experimental designs using clinically relevant doses of glucose. These clinical and experimental findings in conjunction with the wide availability of a rapid bedside screen for hypoglycemia provide the rationale for an alteration in the standard of care. The empiric administration of glucose should be avoided in patients at risk for cerebral ischemia, such as those with acute stroke, impending cardiac arrest, or severe hypotension or receiving CPR. A bedside fingerstick blood glucose estimation should be performed immediately on all patients presenting with altered mental status. The administration of 50% dextrose should be reserved for those patients in whom hypoglycemia is demonstrated; this practice will uphold Hippocrates' most basic principle of clinical medicine, "The physician must ... do no harm." PMID- 2188540 TI - A prospective study of hand-held Doppler ultrasonography by emergency physicians in the evaluation of suspected deep-vein thrombosis. AB - A prospective study was conducted in the emergency departments of two community hospitals to assess the accuracy of Doppler ultrasonography performed by emergency physicians in the evaluation of patients with symptoms suggestive of deep-vein thrombosis. Seventy-eight extremities in 76 patients were evaluated by both Doppler ultrasonography and contrast venography. Thirty-six Doppler examinations were normal, 26 were abnormal, and 15 were equivocal. Of the unequivocal examinations, three were false-negative and nine were false-positive. These data represent a sensitivity of 85%, specificity of 79%, negative predictive value of 92%, and positive predictive value of 65%. Negative predictive value improved to 100% among a subgroup of low-risk patients, and positive predictive value improved to 80% among a subgroup of high-risk patients. Our study suggests that Doppler ultrasonography is highly predictive of a negative venogram, particularly in the low-risk patient. Further study with a larger population is needed. The availability and noninvasiveness of Doppler ultrasonography make it a useful adjunct in the evaluation of suspected deep-vein thrombosis in the ED. PMID- 2188541 TI - Value of initial ECG findings and plasma drug levels in cyclic antidepressant overdose. AB - Electrocardiographic changes and quantitative plasma drug levels associated with cyclic antidepressant (TCA) overdose have been the subject of many reports in the medical literature. Heart rate, QRS duration, QT interval, and most recently, the terminal 40 ms QRS (T40) axis have been reported to be valuable indicators in TCA overdose. The value of plasma drug levels and their ability to predict complications has been debated. To evaluate the discriminant and predictive abilities of ECG parameters and quantitative drug levels in a large series of TCA overdoses, we retrospectively reviewed the charts of all overdose patients admitted to ICU in our facility during a 30-month study period. The TCA-positive group (187) had statistically significant differences (P less than .001) from the TCA-negative group (171) in heart rate, QRS duration, QTc, and T40 axis. However, none of these parameters could correctly classify more than 66% of cases. The sensitivity and specificity of the T40 axis were found to be only 29% and 83%, respectively. Correlation coefficients for plasma quantitative TCA levels by ECG parameter yielded an R of less than .33 in all cases. QRS duration of 100 ms or more and heart rate of 100 or more, or TCA level of 1,000 ng/mL or more, were present in all of a few patients with complications. We conclude that ECG parameters cannot be relied on to include or exclude the diagnosis of TCA overdose and that TCA levels do not correlate with ECG parameters. PMID- 2188542 TI - Detection of soft-tissue foreign bodies by plain radiography, xerography, computed tomography, and ultrasonography. AB - Detection of a soft-tissue foreign body is common yet often difficult, particularly when the foreign material is not radiopaque. Various imaging modalities have been advocated for detecting foreign bodies that are not revealed by plain radiography. The abilities of plain radiography, xerography, computed tomography, and ultrasonography to detect glass, wooden, and plastic foreign bodies in an in vitro preparation are compared. While all of these imaging techniques demonstrated a glass foreign body, only ultrasonography clearly identified wooden and plastic foreign bodies. PMID- 2188543 TI - Early administration of corticosteroids in emergency room treatment of acute asthma. AB - STUDY OBJECTIVE: To determine the effect of early administration of high-dose intravenous corticosteroids on duration of emergency room treatment and hospital admission rate in patients with acute asthma. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: The emergency room of a large, urban hospital with primary and referral care responsibilities. PATIENTS: Eighty-one patients from 18 to 45 years of age with acute bronchial asthma and without pneumonitis or other serious underlying illnesses were studied on 91 occasions and were randomly assigned to control or experimental groups. INTERVENTIONS: The steroid group received 125 mg of intravenous methylprednisolone whereas the control group received intravenous normal saline 30 minutes after initial treatment. Additional treatment included aerosolized metaproterenol and oral theophylline therapy. Six hours after study entry, remaining patients were treated with 40 mg of intravenous methylprednisolone. Hospitalization was mandatory if total treatment time was greater than 12 hours. MEASUREMENTS AND MAIN RESULTS: Age, sex, peak expiratory flow at entry, and prevalence of recent corticosteroids use were similar in both groups. Duration of emergency room treatment was 6.7 +/- 4.2 (SD) hours in the steroid group and 6.3 +/- 4.1 hours in the control group (P = 0.66). Hospitalization was necessary in 18% (95% CI, 7% to 30%) of the steroid group and in 13% (CI, 3% to 22%) of the control group. Frequency of return visits for acute asthma 2 days after emergency room discharge was 11% (CI, -1% to 22%) in the steroid group and 13% (CI, 2% to 23%) in the control group. CONCLUSIONS: These results fail to show any benefit for early administration of corticosteroids in patients with acute asthma. Routine administration of corticosteroids on initial presentation in such patients may not be warranted. PMID- 2188544 TI - Syncope: current diagnostic evaluation and management. AB - OBJECTIVE: To provide a comprehensive review of the causes, current diagnostic evaluation, and treatment of syncope. DATA IDENTIFICATION: New data and knowledge in this evolving field were critically analyzed by doing a MEDLINE search on syncope supplemented by selective review of English language literature citations in the Index Medicus before 1980. STUDY SELECTION: We reviewed approximately 200 published articles on syncope and closely related topics as well as using our own clinical experience. We selected articles if they addressed the pathophysiology of syncope, classification and causes, differential diagnosis, noninvasive and invasive evaluation, and current therapy. RESULTS OF DATA SYNTHESIS: Syncope is a common clinical problem, occurring in 30% to 50% of the adult population. The prognosis for syncope depends on its cause. Cardiac syncope has the worst prognosis and therefore mandates thorough evaluation and prompt treatment. Diagnostic evaluation is made difficult by the transient nature of the episodes and the many causes. Noninvasive testing reveals the cause of syncope in approximately 50% of cases. More extensive evaluation, including invasive electrophysiologic studies, has assumed a larger role in defining the cause of syncope in selected patients with structural heart disease in whom a noninvasive evaluation has been nondiagnostic. Recently tilt-table studies have been proposed as a clinically useful noninvasive test for vagally mediated syncope. CONCLUSIONS: A rational stepwise diagnostic and therapeutic approach to patients with syncope can be developed by initially doing a careful history and physical examination followed by a noninvasive evaluation and selective use of additional, more specialized or invasive tests. Future research should focus on defining the validity and utility of current diagnostic testing in syncope and on exploring further the pathophysiology of patients with recurrent, unexplained syncope. PMID- 2188545 TI - The American College of Physicians: the first 75 years. PMID- 2188546 TI - [Congenital sensorineural deafness and associated syndromes]. AB - The etiology of perceptive deafness, especially the congenital variety, requires investigation. The presence of a variety of signs associated with deafness constitutes an "associated syndrome" and helps to define a possible genetic origin. These syndromes only represent a small percentage of overall causes of deafness in children, since at most they account for only 10% of cases. Certain syndromes are encountered more often or are well known, others are extremely rare or have only been described recently. The authors report six of these very rare syndromes discovered among their patients: a KID syndrome, a Leopard syndrome, a Norrie syndrome, a Jervell and Lange Nielsen syndrome, a recently described entity called CEE with deafness and an External Neuro-Cochleo-Pancreatic syndrome which would not appear to have been previously described. PMID- 2188547 TI - [Development of tone curves in sensorineural deafness in children]. AB - The authors reviews 239 cases of child sensorineural deafness (478 ears studied both separately and in correlation with the controlateral ear) to try and identify the evolutionary trend of the tone curves throughout the follow-up period, which spanned nearly 20 years in some cases. The difficulties encountered in this study were due to several factors, namely the problem involving very accurate assessment in very young children, the high incidence of tubotympanal disease in the very young, the hard to obtain definition and quantitative evaluation of the notion of progressiveness, as well as the need to analyze the evolutionary patterns in global terms (mean hearing loss), from one frequency to the next and from one ear to the other, since such tone loss patterns are not always symmetric. The authors state their opinion derived from a large number of cases regarding a situation, which characterizes a relatively frequent (over 25% of cases) aggravation of perceptive hearing loss in children. PMID- 2188548 TI - [Linear mastocytosis of the Telangiectasia macularis eruptiva perstanstype]. PMID- 2188549 TI - [Ross's syndrome. Apropos of a case]. PMID- 2188551 TI - [Pseudoxanthoma elasticum]. PMID- 2188550 TI - [Dermatologists facing the risk of viral transmission. Analysis of the precautionary measures of 472 practitioners]. AB - On the occasion of the "Journees Dermatologiques de Paris", in March 1988 we designed a survey to evaluate the sterile practices of French dermatologists in the "AIDS era". During the two days meeting, attended by 2,584 participants, 472 questionnaire forms were filled in (answer rate 18.5 p. 100). Among responders 43 p. 100 were exclusively office-based, 13 p. 100 only worked in hospitals, and 44 p. 100 were practicing both in office and hospital. The overall utilisation of gloves by French dermatologists remained highly variable, depending on the procedure. For example 6.7 p. 100 of responders reported never using gloves for excisions, 13 p. 100 for shave biopsies, 18 p. 100 for punch biopsies, 40 p. 100 for curettage and 47 p. 100 for electrocoagulation. Five per cent of the dermatologists surveyed did not sterilize their curettes regularly and 42 p. 100 their electrocoagulation needles. Heat sterilization was the most commonly used, in 69 p. 100 of cases for curettes and 42 p. 100 for electrocoagulation needles. On the other hand, chemical tray sterilization was used in 58 p. 100 of the cases for electrocoagulation needles, and in 31 p. 100 for curettes. For chemical sterilization, 63 p. 100 of responders used alcohol, 15 p. 100 glutaraldehyde, 15 p. 100 sodium hydrochloride, and 7 p. 100 other agents, mainly quartenary ammonium compounds. Twelve per cent of the physicians surveyed have adopted the practice of using a single electrocoagulation needle, belonging to each patient, for long term repeated procedures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188552 TI - [Melanoma in children. Realities, borderlines and diagnostic difficulties]. PMID- 2188553 TI - [Early surgical indications in the treatment of congenital giant pigmented nevi]. PMID- 2188554 TI - [Treatment of condylomata acuminata: efficacy of the carbon dioxide laser]. AB - The treatment of condyloma acuminatum may be long and tiresome owing to frequent recurrences, and the multiple physical or chemical therapies utilized bear witness to the difficulties often encountered in trying to eradicate the lesions. CO2 laser is a therapeutic alternative with some advantages, such as minimal peripheral thermal necrosis with a lower risk of scar or stricture, haemostasis and perhaps sterilizing effect. Between 1985 and 1987, 69 patients (58 men and 11 women; mean age 29 years) treated with CO2 laser and followed up for at least 6 months without recurrence entered our study. All patients had multiple lesions located in the genital region in 32 cases, in the anal region in 22 cases and in both the genital and anal regions in 15 cases. The majority of patients (85%) had been referred to us owing to failure of previous treatments. We used the CO2 laser coupled with a hand-piece, working by continuous emission, with a power of 300 to 800 watts/sq.cm. Superficial vaporization of the area around the condyloma was systematically performed. Seventy-seven percent of the patients were treated under local anaesthesia. In 16 patients with intra-anal or profuse ano-genital lesions the first vaporization was carried out under general anaesthesia. Twenty two patients (32%) were cured in one session and 19 (28%) in two sessions. Twenty eight patients had several recurrences requiring repeated treatments (3 to 5 in 17 cases, 6 to 10 in 10 cases, 31 in 1 case) over a 2 to 17 months' period. No major complications, notably scarring, were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188555 TI - [Fracture of the spine and growth in children]. PMID- 2188556 TI - [The role of colorectal resection in severe constipation after promontory rectopexy]. AB - Abdominal rectopexy to the promontory is an effective treatment for total rectal prolapse, internal procidentia and solitary ulcer. This paper is designed to stress the risk of severe constipation following rectopexy, a complication which required surgical resection in 5 cases. This raises the problems of the physiological mechanisms of this complication, the definition of a possible high risk population (young women, patients who were constipated preoperatively?), and an alternative to promontory rectopexy: sacral fixation of the rectum, associated sigmoidectomy, Delorme's operation? PMID- 2188557 TI - [Traumatic rupture of the bladder. Apropos of 11 cases]. AB - Eleven cases of rupture of bladder were observed within 7 years. Four of them were due to a direct trauma on a full bladder (group I), the other seven occurred during a complex trauma, constantly with a fracture of the pelvis (group II). In group I, the rupture was situated on the apex of the bladder. The symptoms were a suprapubic pain in four patients, a hematuria in two, and an anuria in one. In the four patients, intraperitoneal fluid was clinically evident, and confirmed ultrasonographically. An urography was performed in two patients and showed an intraperitoneal leak in our patient, and intravesical clots in the other one. The four patients were operated on within 48 hours, and were successfully treated by suture and vesical catheter. In group II, the vesical injury was revealed by hematuria (2 patients) hemorragic shock (2 patients) or both (2 patients). In the last patient, an abdominal pain after 10 days was the only symptom. Clinical signs of hemoperitoneum were present in only four patients and were confirmed ultrasonographically in two out of five patients. The urogram was normal in two of four patients. In one patient it showed a small bladder, and in another one a vesical leak. Five patients were operated on among where three in emergency and two after 9 and 10 days. Four patients with intraperitoneal rupture were successfully tread by suture of the bladder. Among three patients with extraperitoneal rupture, one had an additional tear of the mesentery and died from intravascular coagulation, the second was successfully treated by a suture, and the last one by a vesical catheter only.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188558 TI - [Isolated retroperitoneal hydatid cyst. Apropos of a case]. AB - This is a report of a rarely observed localisation of hydatid cyst: the retroperitoneal space. The hypotheses of pathogenesis advanced are reviewed and the interest of intravenous urography and ultrasonography in the diagnosis is emphasized. Surgery the only treatment, consists of partial resection of the cyst. PMID- 2188559 TI - [Value of the assay of serum myoglobin in recent myocardial infarction]. AB - The serum myoglobin (MG) was assayed by the radio-immunological method in 30 patients, all victims of a recent myocardial infarction (MI) and in 30 tests subjects suffering (21 cases) or not (9 cases) from heart diseases, but none from myocardial infarction (MI). The blood samples have been collected on hospital admission of the patient, then every four hours during the first 48 hours and finally, every 12 hours from the 48th to 72nd hour. The normal value is less than 85 micrograms/l. The creatine-kinase (CK), the aspartate aminotransferase (ASAT), the alanine aminotransferase (ALAT) and the lactate dehydrogenase (LDH) were also assayed each time. In MI, there is a significant increase in the serum MG level (731 +/- 323 micrograms/l against 174 +/- 198 micrograms/l in the test subjects; p less than 0.001). The sensitivity of this assay reaches 97%, its specificity 80%, its positive predictive value 83% and its negative predictive value 96%. Starting from the beginning of the characteristic pain of infarction, the MG level exceeds the normal values after 3.3 +/- 1.6 hours, reaches its maximum after 9.3 +/- 3.7 hours and comes back to normal after 38 +/- 8.1 hours. On the other hand, the MG level does not enable any conclusion regarding either the transmural/not transmural nature, or the site, or the acuteness of the MI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188560 TI - [Constrictive pericarditis: study by Doppler echography of blood flow in the supra-hepatic veins]. AB - The blood flow rate in the supra-hepatic veins has been measured by Doppler ultrasound in 11 subjects suffering from more or less advanced constrictive pericarditis; the results were compared to those obtained with normal subjects. In all the pathological cases, the flow rate curve shows the following modifications: a slight decrease in the X peak, which is related to the blood "demand" caused by the decrease in the ventricular volume during the ejection, and a correlative increase in the Y peak, contemporaneous of the ventricular filling up. In the patients in which the pericarditis has not reached a marked stage of constriction, the intra-thoracic ventilatory pressure variations still exert a certain influence on the supra-hepatic blood flow rate; on the other hand, this influence is suppressed when the constriction is complete. These phenomena are parallel to the pressure modifications observed by catheterism and to those of the mitral and tricuspid transvalvular flow. The advantage of measuring the blood flow rate in the supra-hepatic veins lies in the fact that the access, for ultrasound analysis, to these vessels is quicker and more constant than to the heart valves. This method seems therefore to be an interesting one to assess the stage of development of the constricting pericarditis. PMID- 2188561 TI - [Painless obstruction of the left coronary trunk. Apropos of a case]. AB - The originality of this observation of the complete occlusion of the left coronary artery lies in its painless character on the angina level. The affection was revealed by the clinical manifestations of the left ventricular failure in severe ischaemic myocardiopathy. The diagnosis of the ischaemia was made during the physical exercise test coupled with thallium scintigraphy. It therefore seems to be a form of silent ischaemia in major coronary lesions, for which the only conceivable therapeutic option is surgery, considering the particularly pessimistic spontaneous prognosis. PMID- 2188563 TI - Mechanisms of hemolysis in liver disease. AB - Liver disease, particularly alcoholic cirrhosis, is associated with a number of interesting chemical changes which result in structural and metabolic abnormalities of the erythrocyte membrane leading to microscopically observable cell shape changes and hemolytic anemia varying from very mild to potentially lethal. Increase in unesterified serum cholesterol owing to lecithin cholesterol acyl transferase (LCAT) deficiency in cirrhosis leads to expansion of the lipid bilayer and macrocytosis without megaloblastic changes in precursors. Substitutions of phosphatidyl choline (PC) moieties in the erythrocyte lipid bilayer lead to echinocytes (disaturated PC) or to stomatocytes (diunsaturated PC). In some patients, high density lipoprotein (HDL) abnormalities lead to erythrocyte surface changes causing rapid formation of echinocytes. The rapidity and reversibility of these changes suggest blockade of metabolic transport channels critical to the maintenance of erythrocyte membrane shape. Metabolic changes involving vitamin E deficiency leading to lipid peroxidation and pyruvate kinase instability leading to adenosine triphosphate (ATP) reduction have also been invoked to explain hemolysis associated with acute liver damage. The most severe hemolysis in liver disease is associated with acanthocytes (spur cells) and a marked imbalance in cholesterol-phospholipid ratio. These patients usually have hypersplenism, as well as rigid erythrocyte membrane transformations which are irreversible. Any of the other erythrocyte membrane shape changes described appear to be reversible if the liver disease abates, but they too may become irreversible if bits of projecting membrane are repeatedly removed by the macrophages of an enlarged spleen. PMID- 2188562 TI - Beta 2-microglobulin: its significance and clinical usefulness. AB - beta 2-Microglobulin (beta 2M), an interesting and underutilized metabolite, can be used in assessing renal function, particularly in kidney-transplant recipients and in patients suspected of having renal tubulointerstitial disease. It also can serve as a nonspecific but relatively sensitive marker of various neoplastic, inflammatory, and infectious conditions. Early hopes that it would be a useful serum test for malignancy have not been fulfilled, but it does have prognostic value for patients with lymphoproliferative disease, particularly multiple myeloma. More recent reports have suggested a role for beta 2M as a prognostic marker in human immunodeficiency virus (HIV) infection. PMID- 2188564 TI - Malignant lymphomas associated with immunodeficiency states. AB - An increased incidence of malignant lymphomas is common to all types of immunodeficient patients whether they be of the natural or constitutionally occurring type, acquired as in acquired immunodeficiency syndrome (AIDS) or of iatrogenic origin as in organ transplantation. Although there is some degree of heterogeneity, the most characteristic feature of these immunodeficient states is alteration of T-cell cytotoxic function. The malignant lymphomas show a variety of relatively common features, notably: rapid onset following the appearance of the immunodeficient state, a high degree of clinical aggressiveness, and a tendency to present in extranodal sites, particularly the central nervous system (CNS) and gastrointestinal tract. The tumors are almost invariably of B lymphocytic cell origin and while the histologic classifications reflect some diversity, the vast majority of tumors are described as Burkitt-like or diffuse large cell type. There appears to be a high degree of correlation with a preceding fulminant Epstein-Barr virus (EBV) infection resulting in marked B-cell lymphoproliferation in the absence of effective T-cell control. Initially, the B cell proliferation is clearly polyclonal and reactive in nature, although as time evolves, there appears to be selection of oligoclonal and even monoclonal cell populations. Such cells are latently infected with EBV and may express EBV nuclear protein two and latent membrane protein, which are characteristically seen in proliferating B-lymphocytes in response to growth transformation by EBV. While desoxyribonucleic acid (DNA) probes may continue to demonstrate multiple lymphoid clonal populations, it is hypothesized that the hyperproliferative state favors genetic alterations which select out a single malignant clone. This transformed clone is evidenced by expression of a translocated, activated c-myc oncogene and decreased evidence of EBV nuclear protein two and latent membrane protein, that is, characteristics of Burkitt's lymphoma. Other large cell malignant lymphoma phenotypes may show similar findings. While most studies have continued to suggest that EBV plays a key role in the development of non Hodgkin's lymphoma (NHL) of AIDS patients, some recent studies have suggested a less dominant role. Therefore, further exploration of the world of molecular biology will be needed to demonstrate whether other factors, namely additional viruses and/or oncogenes play a similar or significant role in the lymphomas of immunodeficient patients. PMID- 2188565 TI - Maternal platelet antibody levels in neonatal isoimmune thrombocytopenia. AB - A case of neonatal isoimmune thrombocytopenia (NIT) is described in which maternal platelet antibody levels decreased during the course of pregnancy. It is suggested that if this disorder is clinically suspected, maternal serum should be assessed for anti-platelet specificity using immunoblot analysis. PMID- 2188566 TI - Ability of short-term tests to predict carcinogenesis in rodents. PMID- 2188567 TI - Covalent and noncovalent interactions in acute lethal cell injury caused by chemicals. PMID- 2188568 TI - Role of pharmacokinetics in safety evaluation and regulatory considerations. PMID- 2188569 TI - Alcohol and cancer. PMID- 2188570 TI - Genetic and molecular aspects of 2,3,7,8-tetrachlorodibenzo-p-dioxin action. PMID- 2188571 TI - Subtypes of receptors for serotonin. PMID- 2188572 TI - Mutational spectrometry in animal toxicity testing. AB - The microbial geneticists who pioneered the study of mutational spectra have shown us how rich a source of mutagen-specific information it can be for the pharmacologist and toxicologist. Contributions by physical chemists and molecular biologists have led to a practical means to observe mutation spectra directly from the DNA of cultured human cells and this review suggests that the same methodology may be applied successfully to the study of mutations and mutational spectra in tissues of experimental animals and humans. In toxicological testing, the new field of mutational spectrometry offers a previously unattainable level of sensitivity and specificity as well as new tools for dissecting mechanisms of pharmacologic and toxic action. PMID- 2188574 TI - Mechanisms of organophosphorus ester-induced delayed neurotoxicity: type I and type II. AB - Some organophosphorus compounds produce neurologic dysfunctions, known as OPIDN, after a delay period that is accompanied by neuropathic damage in the central and peripheral nervous systems. This group of chemicals may be divided into two classes, Type I and II, based on chemical structure, species selectivity, age sensitivity, the length of latent period, clinical signs, morphology and distribution of neuropathologic lesions, protection with phenylmethyl sulfonyl fluoride, inhibition of neurotoxic esterase, and effect on catecholamine secretion from bovine adrenome-dullary chromaffin cells. The importance of this effect is underlined by the fact that incidents involving more than 40,000 cases of OPIDN in humans have been documented from 1899 to 1989. Most of these compounds are direct or indirect inhibitors of AChE, and produce acute cholinergic effects. Neurologic deficits are characterized by three phases: progressive, stationary, and improvement. Prognosis of OPIDN depends on the extent of damage of the nervous system. Improvement or even recovery of functions may follow mild cases, whereas severe toxicity results in long-lasting neurologic dysfunctions reflecting spinal cord damage. Recent studies have shown that delayed neurotoxic organophosphorus compounds interact with Ca2+/calmodulin kinase II (CaM kinase II), an enzyme responsible for the endogenous phosphorylation of cytoskeletal proteins, i.e. microtubules, neurofilaments, and MAP-2. This leads to an increased activity of CaM kinase II and enhanced phosphorylation of cytoskeletal elements, and eventually in the disassembly of cytoskeletal proteins. The dissociation of cytoskeletal proteins causes increased fast axonal transport in the treated animals resulting in the accumulation of altered cytoskeletal elements in the distal portions of the axon. Abnormal tubulin and neurofilaments are transformed into filamentous polymers and undergo condensation and dissolution. Concomitantly, proliferated endoplasmic reticulum and accumulated mitochondria degenerate and release Ca2+ ions. This leads to Ca2(+)-activated proteolysis of the cytoskeleton and interruption of ionic balance across the axonal membrane resulting in the uptake of water and axonal swelling, which subsequently degenerates. A similar mechanism may cause secondary myelin degeneration. PMID- 2188573 TI - The interaction of the beta-haloethyl benzylamines, xylamine, and DSP-4 with catecholaminergic neurons. PMID- 2188575 TI - The significance of induced forestomach tumors. PMID- 2188576 TI - Altered hepatic foci: their role in murine hepatocarcinogenesis. PMID- 2188577 TI - Excitotoxic amino acids and neuropsychiatric disorders. PMID- 2188578 TI - Biosynthesis and metabolism of endothelium-derived nitric oxide. PMID- 2188579 TI - Interactions between the brain and the immune system. AB - The observations and research described in this communication derive from a nontraditional view of the immune system. It has become abundantly clear that there are probably no organ systems or homeostatic defense mechanisms that are not, in vivo, subject to the influence of interactions between behavioral and physiological events. The complex mechanisms underlying these interactions and their relationship to health and illness, however, are imperfectly understood. The most imperfectly understood, perhaps, are the interrelationships among brain, behavior, and immune processes. Without attempting to cover all the literature, we have used stress effects and conditioning phenomena as illustrations to point out that behavior can influence immune function. We have also described data indicating that the immune system can receive and respond to neural and endocrine signals. Conversely, behavioral, neural, and endocrine responses seem to be influenced by an activated immune system. Thus, a traditional view of immune function that is confined to cellular interactions occurring within lymphoid tissues is insufficient to account for changes in immunity observed in subhuman animals and man under real world conditions. These data question seriously the notion of an autonomous immune system. Most of the research on the regulation of immune responses has been predicated on the assumption that such regulation is accomplished by the interacting components of the immune system itself, e.g. interactions among helper and suppressor T-lymphocytes, B-cells, and accessory cells that can result in the production of antibody and effector T cells. The immune system is, indeed, capable of considerable self-regulation, and immune responses can be made to take place in vitro. The functions of that component of adaptive processes known as the immune system that are of ultimate concern, however, are those that take place in vivo. There are now compelling reasons to believe that in vivo immunoregularity processes influence and are influenced by the neuroendocrine environment in which such processes actually take place--an environment that, on the one hand, can generate signals that resting and/or activated leukocytes can receive, and, on the other hand, is exquisitely sensitive to the individual's perception of and capacity to adapt to the demands of the environment. The immune system appears to be modulated, not only by feedback mechanisms mediated through neural and endocrine processes, but by feedforward mechanisms as well. The immunologic effects of learning, an essential feedforward mechanism, suggest that, like direct neural and endocrine processes, behavior can, under appropriate circumstances, serve an immunoregulatory function in vivo.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2188580 TI - Glutathione: toxicological implications. PMID- 2188581 TI - Muscarinic receptor subtypes. PMID- 2188582 TI - Chloroethylenes: a mechanistic approach to human risk evaluation. PMID- 2188583 TI - Emergence of resistant fecal Escherichia coli in travelers not taking prophylactic antimicrobial agents. AB - Fecal specimens from individuals traveling to Mexico were examined before, during, and after travel for the presence of Escherichia coli resistant to ampicillin, chloramphenicol, gentamicin, kanamycin, streptomycin, sulfonamides, trimethoprim (TMP), and TMP-sulfamethoxazole (TMP-SMX). None of these individuals took prophylactic antibiotics, although 4 of 13 took short courses of an antimicrobial agent for therapy of traveler's diarrhea. With an average of 9.3 E. coli per sample, resistance to all agents tested except gentamicin was shown to increase during the time in Mexico (P less than 0.001 to P less than 0.05). For example, no TMP-resistant (Tmpr) E. coli isolates were found by this method before travel, whereas 57% of the individuals had Tmpr and Tmpr-Smxr E. coli by the final week in Mexico. This increase in resistance occurred regardless of whether an individual took a short course of antimicrobial therapy. This study shows that travel itself, even without the use of prophylactic or therapeutic antimicrobial agents, is associated with the acquisition of resistant E. coli. Travel to developing nations may rival other sources of resistant organisms. PMID- 2188584 TI - 3-Methoxysampangine, a novel antifungal copyrine alkaloid from Cleistopholis patens. AB - Further examination of the active ethanolic extract of the root bark of Cleistopholis patens by using bioassay-directed fractionation resulted in the isolation of a new alkaloid, 3-methoxysampangine (compound I), together with three known alkaloids, eupolauridine (compound II), liriodenine (compound III), and eupolauridine N-oxide (compound IV). The proposed structure of compound I was based on its physicochemical properties and spectral data. 3-Methoxysampangine exhibited significant antifungal activity against Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans. This is the first report of the isolation of liriodenine (compound III) from the root bark of C. patens. PMID- 2188585 TI - Effects of production of abnormal proteins on the rate of killing of Escherichia coli by streptomycin. AB - The role of abnormal membrane proteins in modulating the rate of killing by streptomycin was investigated. Davis et al. (B.D. Davis, L. Chen, and P.T. Tai, Proc. Natl. Acad. Sci. USA 83:6164-6168, 1986) have proposed that misread membrane proteins created by the action of streptomycin on translating ribosomes cause the formation of nonspecific membrane channels which allow increased uptake of the antibiotic and contribute to its bactericidal action. Pretreatment of Escherichia coli with a low concentration of puromycin enhanced the rate of killing by streptomycin. The effect of the pretreatment with puromycin was transient, since approximately normal rates of killing by streptomycin were restored after 30 min of incubation in antibiotic-free medium. This time period correlates with the time required to degrade labile polypeptides in puromycin treated cells. The induction of a specific abnormal malE-lacZ fusion protein, which is capable of disrupting the normal membrane protein secretion process, also increased the rate of killing by streptomycin. Induction of malF-phoA fusion proteins, which have no significant effects on membrane integrity, did not alter susceptibility to streptomycin. These observations suggest that certain abnormal membrane proteins can contribute to the bactericidal action of streptomycin. PMID- 2188586 TI - Activity of sulbactam in combination with ceftriaxone in vitro and in experimental endocarditis caused by Escherichia coli producing SHV-2-like beta lactamase. AB - We studied the efficacy of sulbactam, a beta-lactamase inhibitor, in combination with ceftriaxone in vitro and in experimental endocarditis due to an Escherichia coli strain producing an extended-spectrum beta-lactamase most similar to SHV-2, a new mechanism of resistance to broad-spectrum cephalosporins among members of the family Enterobacteriaceae. In vitro, ceftriaxone demonstrated an important inoculum effect (MICs were 2 and 256 micrograms/ml with 5 X 10(5) and 5 X 10(7) CFU of inoculum per ml, respectively). Sulbactam inhibited the beta-lactamase degradation of ceftriaxone and enhanced the killing by ceftriaxone with both inocula tested. In vivo, sulbactam (100 mg/kg every 8 h) or ceftriaxone (15 or 30 mg/kg every 24 h) alone were ineffective after a 4-day therapy. The addition of sulbactam to ceftriaxone (15 mg/kg) or to the ceftriaxone (15 mg/kg)-netilmicin (6 mg/kg every 24 h) combination produced a reduction of 2 log10 CFU/g of vegetation greater than that produced by therapy without sulbactam. The sulbactam ceftriaxone (30 mg/kg) combination produced a reduction of almost 5 log10 CFU/g of vegetation greater than that produced by single-drug therapy (P less than 0.01), sterilized five of eight vegetations (versus none of seven for ceftriaxone [30 mg/kg] alone; P less than 0.05), and was as effective as the ceftriaxone (15 mg/kg)-sulbactam-netilmicin combination. We concluded that (i) SHV-2 production was responsible for ceftriaxone failure in vivo, probably because of the high inoculum present in vegetations; (ii) sulbactam used in a regimen which provided levels in serum constantly above 4 micrograms/ml and a vegetation/serum peak ratio of approximately 1:3 enhanced the activity of a broad-spectrum cephalosporin in a severe experimental infection; and (iii) the highest dose of ceftriaxone in combination with sulbactam was as effective as the lowest dose of ceftriaxone plus sulbactam plus an aminoglycoside. PMID- 2188587 TI - Influence of beta-lactam antibiotics on serum resistance of K1-positive blood culture isolates of Escherichia coli. AB - The K1-positive strains of Escherichia coli are a group with considerable clinical importance, serum resistance being a common virulence factor of these strains. In the present paper, the influences of cephaloridine, imipenem, and ceftazidime on the serum resistance of eight serum-resistant K1-positive E. coli blood culture isolates with smooth-type lipopolysaccharide were studied. All strains were rendered more serum sensitive by treatment with subinhibitory concentrations of antibiotics. The amount of the reduction of serum resistance was dependent on the concentration of the antibiotic. Amounts of K1 produced under the influence of the antibiotics were measured and were found to be reduced for almost all strains tested. To further test the hypothesis that antibiotic induced reduction of serum resistance is mediated by inhibition of K1 expression, isogenic mutants of one strain were produced by selection for resistance against infection with K1-specific bacteriophages. These mutants were found to be highly serum sensitive. We conclude from this study that beta-lactam antibiotics can render K1-positive serum-resistant strains of E. coli highly serum sensitive and that this effect is mediated by inhibition of K1 expression. PMID- 2188588 TI - The dhfrI trimethoprim resistance gene of Tn7 can be found at specific sites in other genetic surroundings. AB - The dhfrI gene, mediating high-level trimethoprim resistance, was earlier found only on Tn7. Evidence is given here for an alternative location of this gene at a site identical to sites observed earlier for dhfrII on plasmid R388, dhfrV on pLMO20, and aadA on Tn21. All these genes and dhfrI are precisely inserted as discrete GTTA-flanked elements at distinct loci in very conserved surrounding sequences. One of these dhfrI insertions was observed to occur in association with a similarly inserted aadA nucleotidyltransferase gene, which mediates streptomycin and spectinomycin resistance. Close to the insertion site, there is an open reading frame translating into a 337-amino-acid peptide which shows striking similarities to recombinases of the integrase family, sulI, the sulfonamide resistance gene, is very often found close to the insertion point forming a genetic surrounding, originally observed as a part of Tn21-like transposons. The alleged integration mechanism thus provides a recombination pathway for the genetic linkage of sulfonamide and other antibiotic resistance genes, including the most frequently encountered gene for trimethoprim resistance, dhfrI. Furthermore, the newly observed location of dhfrI could shed light on the evolution of the antibiotic resistance region of Tn7, which could be able to take up genes by the same mechanism as that of Tn21-like transposons. PMID- 2188589 TI - Antifungal activity in human cerebrospinal fluid and plasma after intravenous administration of Allium sativum. AB - Commercial Allium sativum (garlic) extract was given intravenously to two patients with cryptococcal meningitis and three patients with other types of meningitis. Plasma titers of anti-Cryptococcus neoformans activity rose twofold over preinfusion titers. Anti-C. neoformans activity was detected in four of five cerebrospinal fluid samples but not in pooled normal cerebrospinal fluid. PMID- 2188590 TI - Randomized, controlled trial of a 10-day course of amifloxacin versus trimethoprim-sulfamethoxazole in the treatment of acute, uncomplicated urinary tract infection. Amifloxacin Multi-Center Trial Group. AB - We conducted a randomized controlled trial of orally administered amifloxacin versus trimethoprimsulfamethoxazole (TMP-SMX) as treatments of acute uncomplicated urinary tract infection in women. Amifloxacin at a dosage of 200 mg twice a day appeared as safe and effective as TMP-SMX, but amifloxacin at 400 mg twice a day tended to cause adverse events more frequently than did TMP-SMX. PMID- 2188592 TI - [Quality of life in cancer patients]. AB - Quality of life (QOL) is defined as "representation of people's day-to-day function". It has four components: physical and occupational functions, social interaction, psychological state, and somatic sensation. QOL can be mathematical presentation of these four component factors. QOL measurement tools (questionnaires) should have core modules as well as disease-specificity, simplicity, validity and reliability. At present, several patients' self assessment questionnaires are widely used practical at the aims to assess what happens in the cancer patients and to improve the cancer treatment. A QOL study trials should be scientific. However, QOL is popular terms that there is a tendency to abuse it, and, therefore, to set up the study to get contradictory results. The author would introduce a practical overview of the tactics to perform a QOL research trial. PMID- 2188591 TI - Continuation of chloroquine-susceptible Plasmodium falciparum parasitemia in volunteers receiving chloroquine therapy. AB - Volunteers infected with a chloroquine-susceptible line of Plasmodium falciparum were administered standard oral chloroquine therapy at the first detection of parasites in the blood. Parasitemias progressed in the face of therapy for up to 5 days and to levels up to 100-fold greater than those at the initiation of treatment. Thereafter, infections cleared without a requirement for additional chemotherapy. This course of infection and response to treatment has not been previously reported and may have been detected because volunteers were exposed to an unusually large number of sporozoites. The observations are consistent with the hypothesis that prolonged parasitemia resulted from the continued release of merozoites from liver. PMID- 2188593 TI - [Advances in surgery of head and neck cancer]. PMID- 2188594 TI - [Breast preserving surgery]. AB - Psychological damage caused by radical mastectomy should be taken into consideration from the point of view of quality of life, in addition to sequelae such as disturbance in movement of the shoulder, lymph edema of the arm. Surgery preserving breast is recommended for resolution of the problem. The histopathological study of eighty seven early breast cancer which is defined by 1.0 cm or less in diameter on palpation revealed that sixty seven patients (77 percent) really had a tumor measuring 1.0 cm or less in the surgical specimen and fifty two patients (60 percent) had an invasion into surrounding tissue limited within 2.0 cm from a border of tumor and three patients (3.5 percent) had an invasion to nipple. The data suggested a possibility of surgery preserving breast for patient with early breast cancer satisfied with following condition: tumor is less than 1.0 cm in diameter; it is situated at least 3.0 cm distant from nipple: no involvement palpable in the axilla: no multiple lesion is found on x.p. mammography and ultrasonography: area with minute punctate calcifications is limited in circle measuring 2.0 cm in diameter. Ten patients underwent subcutaneous mastectomy and four patients had quadrantectomy and axillary dissection. A patient had local recurrence, at median follow-up time twenty three months range from three months to 36 months. PMID- 2188595 TI - [Evaluation and problems of segmental mastectomy of breast cancer from the viewpoint of quality of life]. PMID- 2188596 TI - [Developments in the surgical treatment of rectal cancer in view of the quality of life]. AB - The quality of life of patients who had undergone a primary radical resection of the rectum for cancer was restricted by colostomy, urinary incontinence or sexual disturbance. This paper describes the developments and surgical results of sphincter saving operation and nerve preserving operation for rectal cancer. 1) Sphincter saving operation: With the advent of modern sphincter saving techniques such as low anterior resection and stapling technique, abdomino-perineal resection of the rectum are no longer necessary for the treatment of nearly all tumors of rectosigmoid, three of four tumors of the upper rectum and one of five tumors of the lower rectum. At low anterior resection of the rectum, in general principle, the affected parts of the diseased rectum were resected with a macroscopically free margin of at least 3 cm on anal side of the cancer. Recurrence rates of anterior resection were fewer than those of abdomino-perineal resection, and five year survival rates after AR were better than those of after APR. 2) Autonomic nerve preserving operation: As it is impossible to remove the internal iliac lymph-nodes completely without disturbing the underlying pelvic plexus, an autonomic nerve preserving operation was done unless there was microscopic lymphatic gland involvement by frozen section. Urinary bladder function was impaired in 80% of patients after extended lateral dissection without nerve preservation whereas it was unaffected in 14 of 16 patients after nerve preserving operation. Six of seven male patients with nerve preserving operation retained potency, but only one was capable of ejaculation. PMID- 2188597 TI - [Rectal cancer]. PMID- 2188599 TI - [Metastatic brain tumors--recent trends]. PMID- 2188598 TI - [Cervical cancer]. AB - Although the surgical treatment for the uterine cervical carcinoma has been accepted as until recently one of the most effective therapies in terms of radicality, various complications following the operation have tormented patients for a long time, resulting in the deterioration of the quality of their lives. The complications include a loss or an impairment of fecundability, morbidities due to the castration, problems of sexual life, urinary disturbances such as dysuria, incontinence and a loss of feeling of urgency, renal dysfunction, persistent constipation and lymphedema on legs. The serious psychological handicaps are included also. During many years, however, the accumulation of the knowledge which is related to a development of the cancer, recognition of the localisation and an extent of the lesion and prognostic factors, has encouraged the developments of improved methods to keep the essential physiological functions and avoiding a loss of radicality. Those are a laser therapy, retaining of ovaries and preservation of pelvic autonomic nerves including bladder branches. Here, indications, methods and the clinical results of those improved surgical methods are presented and the problems remaining to be resolved are discussed. PMID- 2188600 TI - [Local treatment of metastatic bone tumors]. PMID- 2188601 TI - [Recent advances in rehabilitation of head and neck cancer patients]. AB - This paper describes recent advances in surgical and behavioral rehabilitation for voice, speech and swallowing disorders caused by surgeries for head and neck cancer. Voice disorders result from total laryngectomy, partial laryngectomy and vocal fold laser surgery. Voice prostheses have been recently employed as one of the choices for laryngectomized patients. Surgical reconstruction and voice therapy are the modalities for voice disorders following partial laryngectomy. Dysphonia caused by laser surgery is treated by means of voice therapy. Speech disorders occur following extensive surgery for cancers of the oral cavity and oropharynx. Reconstructive surgery and speech therapy are the modalities to be employed. Swallowing problems are caused by supraglottic horizontal laryngectomy, partial laryngopharyngectomy, extensive surgery for cancers of the oral cavity and oropharynx, surgery for parotid gland and skin cancers associated with a section of the vagus nerve and surgery for esophageal cancers. Surgical treatment and swallow therapy are employed. Surgical treatment is divided into five groups: surgery for velopharyngeal incompetence, those for glottic incompetence, laryngeal suspension surgery, narrowing surgery of the pharynx and cricopharyngeal myotomy. Some cases are described for each treatment modality. PMID- 2188602 TI - [Tongue reconstruction and its functional evaluation following surgery]. PMID- 2188604 TI - [Rehabilitation of the ostomate]. PMID- 2188603 TI - [Colostomy devices for the extracorporeal organ]. AB - Colostomy devices are classified as follows: One-piece and two-piece by structure; Closed, open-end or straight, open-top, drainable, and mini by pouch function. The one-piece device is simple and convenient (disposable) but not cheap; The two-piece one has various exchangeable pouches but some skill is necessary for fitting a pouch to the flange. A closed pouch is disposal en bloc, while an open pouch allows a hand to be inserted several times. The drainable pouch is useful for draining faeces easily with water, while a mini-pouch is unobtrusive and attractive. The skin barrier has been used frequently as a part of the device. Its contents are hydrophilic colloid, hydrophobic colloid and agglutinant. The barrier functioning is dependent on content-ratio and on structure. The latter is classified as blend, laminate, swiss-roll, polka-dot, and froth in type. The apparatus must be used for individual colostomy, utilizing the characteristics based on its specificity; an open-type one-piece unit is used with skin barrier for a postoperative colostomy in the first week, a drainable type, two-piece unit for another week following suture removal or for diarrhea, and a closed type for rehabilitation. This procedure is called a pouch total system. The irrigation method is good for a scheduled defecation and for peri stomal dermatitis and for a deformed stoma, but takes more than a half hour and needs a special toilet for irrigation. Indication of the method is for a young ostomate, a sportsman, a field worker, a neurotic or myosophobic person and so on. Today a pouch-free natural defecation method is becoming popular; a kind of stopper is used for a colostomy. This is a foam plug which expands to block feces and eliminates noise and odor. The method is good for pouch-free living, but fecal leakage is encountered in diarrhea. PMID- 2188605 TI - [Sexual dysfunction following radical operation for cancer of the rectum and colon]. AB - Sexual dysfunction frequently occurs following radical operation for cancer of intrapelvic organs. However, the number of impotent patients with colon and rectal cancer who actually visited our Reproduction Center complaining of impotence after operation accounted for only 31 (1.8%) out of the 1,686 impotent cases during past 8 years; of these 31 patients who complained of impotence after operation by Miles method, 79% were considered to suffer from organic impotence, while 62% of those having undergone anterior resection suffered organic impotence. Even in cases in whom no erection occurs due to some disorder in the nervous system, intracavernous injection treatment using vasoactive agents (papaverine or prostaglandin E1) can be effective if the vascular system is normal. In cases which do not react to this treatment, intrapenile transplantation of various silicone prostheses is tried. Moreover, administration of sympathomimetic agents (imipramine and so on) is undertaken in cases with retrograde ejaculation, among those with ejaculatory disorders, and if no effect is obtained by this administration, artificial insemination is tried using semen ejaculated into the bladder. In cases in whom no ejaculation occurs, even into the bladder, artificial ejaculation is attempted by spinal infusion of prostigmin, and when no effect is obtained, artificial insemination is tried using semen retained in an artificial spermatocele implanted in the tail of the epididymis. PMID- 2188606 TI - [Total replacement of the bladder with an intestinal pouch for normal micturition after cystectomy]. AB - Patients who have undergone cystectomy require some form of urinary diversion, an ileal conduit being the most common. A disadvantage of a conduit, however, is that it necessitates wearing an external appliance. A continent ileal urinary reservoir (Kock pouch) has recently been introduced to overcome the ileal conduit problem. Certain problems arising with a Kock pouch, however, are the presence of stoma that must be intermittently self-catheterized, the technical difficulty of the operation and the possible failure of the efferent nipple valve to function. Another method of urinary diversion is ureterosigmoidostomy which initially seemed a safe, simple operation that ensured urinary continence. Serious problems of electrolyte imbalance, urinary tract infections, formation of renal calculi and so forth, however, have caused many urologists to abandon this procedure. A third method is the construction of an internal reservoir from an intestinal segment anastomosed to the urethra, thus avoiding any stoma. Between May 1987 and August 1989, 15 male patients aged 36-69 years underwent an operation for total replacement of the bladder with an intestinal pouch for normal micturition after cystectomy. Of these 13 patients, the detubularized ileocecocolic segment was used as the internal reservoir and, in the other two, the ileum or the sigmoid colon was used because of severe adhesion of the ascending colon due to previous surgery. Three months after surgery, most patients had a vesical capacity of 300 ml or more and could excrete a maximum 200-300 ml urine at one voiding. Daytime continence was achieved in 14 patients in three months, and nighttime continence in 11 patients in six months. No abnormalities in serum electrolytes except mild hyperchloremia in one patient, acid-base balance or renal function were observed during follow-up periods of 2-27 months. The patients were enthusiastic about this procedure. The follow-up periods have been short, but this method seems promising as a new internal diversion. PMID- 2188607 TI - [Problems of cancer treatment in the elderly from the viewpoint of the chemotherapist--focusing on malignant lymphomas as a model of chemotherapy]. PMID- 2188608 TI - [Indications for endoscopic treatment of early gastric cancer in the aged]. AB - There are few data on the quality of life of patients with early gastric cancer before and after surgery or endoscopic treatment. We reported the long term effect of endoscopic laser therapy as a local curative procedure and discussed appropriate treatment of choice for early gastric cancer in the aged more than 70 years old based on the results of a comparative study of a group of 56 endoscopically treated group of patients and a group of 57 surgically treated patients. Fifty-six patients with endoscopically diagnosed early gastric cancer whose surgical risk was critical or who refused surgery were treated by either photocoagulative effect of Nd:YAG laser or photodynamic therapy with hematoporphyrin derivative and argon dye laser (PDT) or both. The efficacy (negative biopsy for cancer) of laser therapy is 73% at present. All the lesions of superficially elevated mucosal cancer less than 20mm and well demarcated flat or superficially depressed mucosal cancer less than 10 mm (10 elevated lesions, 8 flat or depressed lesions) were completely eradicated and negative for cancer on follow-up biopsy for more than 12 months. Risks of lymph-node metastasis in these lesions are reportedly negligible. Fourteen of the 56 patients (25%) treated by lasers died within 5 years after the initial therapy. Two of them died of gastric cancers too large to eradicate and were presumed to have submucosal invasion. On the other hand, 11 of 57 (19%) treated by surgery died within 5 years following surgery. One patient died from surgery and another of gastric cancer. Quality of life score did not decrease when the patients were treated by lasers but did so statistically significantly in the surgically treated group of patients. Although surgical death in the aged has decreased, death associated with surgical complications is significantly higher than with patients younger than 69 years old. Therefore, we conclude that endoscopic therapy is the treatment of choice for early gastric cancer as a local curative procedure in the aged, if they have a curable lesion as mentioned above. PMID- 2188609 TI - [Endoscopic surgery for gastric cancer in the high age group]. PMID- 2188610 TI - [Recent advances in cancer treatment from the viewpoint of the quality of life. Introduction]. PMID- 2188611 TI - ["Quality of life" of long term survivors of childhood cancer]. PMID- 2188612 TI - [Immunotherapy from the point of view of quality of life]. PMID- 2188613 TI - [Indication of BMT and/or CSF for the recovery of radiation-injured hematopoietic stem cells]. PMID- 2188614 TI - [Cardiotoxicity and pulmonary toxicity of chemotherapy]. AB - Recently, the quality of life of a cancer patient has been extensively discussed. Especially, side effects of chemotherapy are major problems of cancer patients. Cardiotoxicity of adriamycin and pulmonary toxicity of bleomycin are not common side effects of chemotherapy, but they can be devastating, particularly, when they occur in a patient who has been cured of cancer. Therefore, we tried to demonstrate the efficacy of cardiac or pulmonary monitoring in early detection of the toxicity. In conclusion, now non-invasive and invasive standard methods of monitoring have yet to be convincingly established, because most methods are either of no predictive value or too sensitive. Moreover, to date an effective prophylaxis of cardiotoxicity or pulmonary toxicity is still lacking. Exact evaluation of risk factors and thorough cardiac or pulmonary monitoring are necessary in patients under chemotherapy. PMID- 2188615 TI - [The toxicity of anticancer chemotherapeutic agents to the genitourinary organs]. PMID- 2188616 TI - [Effect of sodium thiosulfate on the anti-tumor effect and nephrotoxicity of CDDP in human gastric cancer]. PMID- 2188617 TI - [Multicentric bone chloroma disclosed by pleural cytology]. AB - We report a case of granulocytic sarcoma of the bone with pleural involvement diagnosed upon cytologic analysis of the pleural fluid (centrifugation spots stained by May-Grunwald-Giemsa) and confirmed by more complex investigations, i.e., demonstration of granulomonocytic membrane antigens by immunohistochemical monoclonal antibody techniques on frozen sections of the tumor. This case draws attention to the value of cytologic studies in granulocytic sarcomas whose histologic features are suggestive of lymphoma. PMID- 2188618 TI - [Gastric xanthelasma. Apropos of 2 of our cases]. AB - On the basis of two personal cases and a review of the literature, we have attempted to define endoscopic and histologic features in gastric xanthelasma. The various etiopathogenic hypotheses published in the literature are reviewed and others are suggested. Attention is drawn to the differential diagnosis with mucus-secreting cell carcinoma. Use of stains for mucus in such lesions is recommended to confirm the diagnosis. PMID- 2188619 TI - Salivary gland masses: the diagnostic value of fine-needle aspiration cytology. AB - A series of 165 needle aspirates (134 from the parotid gland, 26 from the submandibular glands, and nine from the palate) was studied. Seventeen aspirates (12.14%) were inadequate for evaluation; 25 were excluded because they came from branchial cysts. Of the remaining 123 samples from major and minor salivary glands, 107 (76.42%) were negative for malignancy and 16 (11.42%) were positive. Benign, non-neoplastic lesions were diagnosed in 53.27% of the aspirates and benign tumors in 46.72%. The cytodiagnoses were compared with the subsequent histological findings in ten of the 57 non-neoplastic lesions, 16 of the 50 benign neoplasms, and ten of the 16 malignant neoplasms. Despite problems of interpretation, in all cases where comparison was possible, the cytodiagnoses were confirmed by the histologic report. Fine-needle aspiration biopsy is superior to other investigations such as scialography, computed tomography (CT) and CT scialography, commonly used in salivary gland disease. As underlined by the results of this study, aspiration biopsy cytology will identify lesions that are not clinically obvious and provide the surgeon with the required preoperative information. PMID- 2188620 TI - [Angiosarcoma of the pericardium. Anatomoclinical study of a case]. AB - We report a case of angiosarcoma of the pericardium in a 62-year-old man. Although the lack of myocardial adhesions allowed complete surgical exeresis, and despite chemotherapy, the patient died three months later because of early recurrence. Large, undifferentiated areas were found within the tumor, raising diagnostic problems with other malignant tumors of the heart. Histochemical, immunohistochemical, and ultrastructural studies confirmed the diagnosis of angiosarcoma. PMID- 2188621 TI - [Melanoma of the vagina. Apropos of a case and review of the literature]. AB - We describe the unusual case of a 60-year-old woman with malignant melanoma of the vagina and positive right inguinal lymph nodes. Etiopathogenesis of this lesion, prognostic factors, and therapeutic attitude, are discussed in the light of data from the literature and the case reported herein. PMID- 2188622 TI - [Immunohistochemical characteristics of malignant melanoma. A study of 40 cases and review of the literature]. AB - An immunohistochemical study of 40 primary and secondary malignant melanomas in 27 patients, with routinely-used monoclonal antibodies, demonstrated the antigenic pattern exhibited by these tumors, as well as the frequency of aberrant positivities for epithelial cell markers. The following results were found: 95% of melanomas stained positively for S100 protein and vimentin, which is the characteristic immunohistochemical pattern in melanomas. In most cases, the primary tumor and its metastases in a given patient had the same antigenic phenotype. As for epithelial markers, 10% of melanomas stained positively for KL1 and 27.5% for EMA. Despite this relatively high frequency of KL1 and EMA positivities, in practice, simultaneous positivity for S100 protein and vimentin, confronted with the patient's history and with histologic features, firmly establishes the diagnosis of malignant melanoma in virtually all cases. PMID- 2188623 TI - Osteoporosis and arthritis. PMID- 2188625 TI - [Ethical problems in clinical research]. PMID- 2188624 TI - Drug toxicity. PMID- 2188626 TI - [The heart and diabetes mellitus]. AB - The atherosclerotic process in the diabetic patient, is more common, it is noticed at early ages, advances more rapidly and almost equally affects males and females. This data, can not be explained on the basis of the association with other coronary heart disease risk factors, there is an intrinsic atherogenic factor attributed to diabetes, and can be related, to the early hyperinsulinemia, coagulation and lipid disorders, hyperglycemia or diabetic microangiopathy. Coronary heart disease has an increased prevalence in diabetic patients, that is not related with diabetes duration or the type of treatment. Early and late morbimortality after acute myocardial infarction and/or revascularization surgery is twice as common in the diabetic patient. Diabetic cardiomyopathy related to small vessels disease is still a matter of controversy and many authors doubt about its relevance in clinical practice. The presence of autonomic neuropathy with the cardiovascular denervation syndrome carries a poor prognosis. Early cardiovascular changes in asymptomatic patients, are detected with non-invasive test, and can help to introduce measures to protect individuals at a greater risk. PMID- 2188627 TI - [Model of bacteriologic effectiveness testing of disinfectants for veterinary medicine]. AB - Proper evaluation of effectiveness of chemical disinfectants depends on availability of a standardised test methodology which can provide reproducible values. The binding rules and regulations for testing and acceptance under the heading of "Methods for Testing Chemical Disinfectants for Veterinary Medicine" (team of authors, 1987) have resulted from years of experimental research in the field of disinfectant development. They include a model for bacteriological laboratory testing which is described in this paper, with complementary reference being made to experimental planning and appraisal of disinfection success. An account is given of preparatory testing, using agar diffusion and serial dilution tests, and of main testing, using suspension and microorganism carrier tests. The RF% microorganism reduction rate is introduced for appraisal of disinfection success. With differentiated initial germ counts, the comparability of experimental results provided by RF% has proved to be superior to that obtainable from conventional calculation. PMID- 2188628 TI - [Experimental studies of the modification of the reproductive process during early pregnancy in young sows using the Gn-RH analog Gonaret "Berlin Chemistry"]. AB - Thirty-three inseminated gilts received treatment on the tenth day of gravidity, using 50 micrograms of Gonavet "Berlin-Chemie", a gonadotropin releasing hormone analogue. They were all slaughtered on the 32nd or 33rd day of gravidity. The number of pregnant sows was higher by 4.6 percent than that among 29 controls kept in parallel. Embryo survival rate of treated sows was 12.3 percent above that recorded from the controls. No findings indicative of any detrimental effect of treatment were recordable from the ovaries of all sows slaughtered. The results so far obtained are likely to encourage more investigations on controllability of embryonic development in swine. PMID- 2188629 TI - [Extrahepatic elevation of transaminases]. PMID- 2188630 TI - [Acute lymphoblastic leukemia in children. Results of a protocol including bone marrow transplantation during the first remission in high-risk forms for relapse]. AB - Ninety-two previously untreated children with ALL were admitted to the same institution between November 1984 and November 1988. According to early prognostic factors, patients were divided into 3 groups: group 1 at "low risk" for relapse (n = 18), group 2 at "intermediate risk" (n = 62) and group 3 at "high risk" (n = 12). Every patient received an 8 week-long induction chemotherapy; after CNS prophylaxis, groups 1 and 2 children received a consolidation chemotherapy and then a classical maintenance treatment. Group 3 patients were selected to receive a bone-marrow transplantation during their first remission because of the presence, at diagnosis, of at least one of the following criteria: hyperleukocytosis greater than 100,000 (7 cases), translocation t(1;19) and t(4;11) (2 cases), adolescents (2 cases), no remission at day 30 (2 cases). Ninety-one of 92 children achieved a complete remission and none died during induction therapy. Probability of leukemia-free survival at 4 years is 73 +/- 7% for the whole patient population and 95%, 71% and 60% for patients of groups 1, 2, and 3 respectively. Persistence or disappearance of leukaemic cells in bone marrow after the initial 15 days of chemotherapy appears to influence the probability of a leukemia-free survival. PMID- 2188631 TI - [Neonatal nemaline myopathy with favorable outcome]. AB - A case of neonatal nemaline myopathy without respiratory distress is reported in a neonate. Its relatively benign course allowed survival without major complications. The discovery of a "central core disease" myopathy in her asymptomatic father confirms the relation between both entities. PMID- 2188632 TI - [IgG subclass deficiencies]. PMID- 2188634 TI - Osteochondritis dissecans of the lateral tibial condyle. Report of a new case and review of the literature. AB - Osteochondritis dissecans (OD) of the lateral tibial condyle is a rare condition. A review of the literature revealed only nine cases in seven patients. We report about a new case. It is widely accepted that this form of OD originates from an accessory center of ossification. Our case supports this theory. Although comparative roentgenograms of the left knee, taken because of complaints in the right one, were interpreted to be normal, retrospective analysis clearly revealed the lateral intercondylar eminence of the left knee to have been irregular many years before the onset of symptoms. Association with a classical OD in the contralateral knee is striking in most of the reported cases. PMID- 2188635 TI - Overview of history of midwifery. PMID- 2188636 TI - "What are the origins of the regulation, training and practice of midwifery in Australia"? PMID- 2188633 TI - Bone transplantation. AB - According to one principle of surgery, the transplantation of vital tissue is the best method of reconstructing a defect. Because of absent immunologic reactions, high osteogenic potency, and preserved stability, transplantation of autogenous bone shows the best results. Necrosis of transplanted bone, leading inevitably to absorption and remodeling of the graft, can be avoided if microsurgically vascularized autogenous bone segments are transferred. Disadvantages are the low availability and the necessity of additional operations. As an alternative, deep frozen allogeneic bone is used. However, this kind of bone shows delayed incorporation based on cellular and humoral immune reactions, and it is also installed into the host bed after overcoming the immune barrier. The risk of microbiological contamination or transmission of unrecognized germs such as HIV is a cause of great expense in bone banking techniques. If one succeeds in reducing (a) the immunologic defense reaction and (b) the risk of infection by sterilization or disinfection without damaging the osteoinductive proteins of bone matrix, the rate of complications can be lowered. Demineralized bone matrix can be used if biomechanical stability is not required. Its ability to induce osteogenesis without a major immune reaction or the risk of transmitting diseases justifies its clinical application. Further intensive research in these areas is unavoidable. PMID- 2188637 TI - Immunochemistry of high molecular-weight human salivary mucin. AB - The purpose of this study was to determine the distribution of mucin glycoprotein 1 (MG1) within submandibular, parotid, labial and palatine salivary tissues. Formalin-fixed and frozen tissue sections were examined histochemically with PAS, Alcian blue and Meyer's mucicarmine, and immunocytochemically with an anti-mucin glycoprotein 1 monoclonal antibody (clone 3/E8). Clone 3/E8 was produced in Balb/c mice using mucin-enriched chromatographic fractions from submandibular sublingual saliva. The monospecificity of 3/E8 was confirmed by immuno-dot blotting and SDS-PAGE/electrophoretic transfer. Clone 3/E8 (IgG1; kappa) was of moderate affinity, and was directed to a carbohydrate-containing, TPCK-trypsin insensitive and pronase-insensitive epitope on this mucin, which was not blood group specific. The location of mucin glycoprotein 1 was determined by both indirect (peroxidase-antiperoxidase) and direct methods. Mucin glycoprotein 1 was localized within all labial acini examined, but was not found within parotid tissues. Histochemical methods stained all submandibular, palatine and labial acini, but immunocytochemistry with monoclonal antibody revealed heterogeneous staining with clone 3/E8 in submandibular and palatine tissues. These findings suggest the presence of mucin glycoprotein 1-specific acinar cell subpopulations within human submandibular and palatine salivary tissues. PMID- 2188638 TI - Continuing tooth eruption and alveolar crest height in an eighteenth-century population from Spitalfields, east London. AB - Earlier studies on dried skulls have shown that continuing eruption occurs throughout life to an extent which appears to compensate for occlusal attrition. Some investigators have interpreted the increasing distance between the tooth cervical margin and the alveolar crest as an indication of horizontal bone loss due to chronic inflammatory periodontal disease. In order to determine whether continuing eruption occurs in the absence of attrition, measurements were made on the jaws of an eighteenth-century population whose tooth wear had been minimal. Horizontal bone loss at the alveolar margin was minimal or absent. Continuing eruption had occurred, indicating that facial height probably increased throughout the life time of the individuals. PMID- 2188639 TI - Polymorphism in 5' flanking region of human insulin gene. Relationships with atherosclerosis, lipid levels, and age in three samples from Denmark. AB - Variations in the DNA sequence flanking the 5' region of the human insulin gene (U- and L-alleles) were studied in relation to atherosclerosis, lipid levels, and age in three groups of atherosclerotic individuals and in nonatherosclerotic controls. The atherosclerotic groups comprised a postmyocardial infarction group with a mean age of 48 years, a group of individuals operated on for carotid stenosis with a mean age of 62 years, and a group of 85-year-olds with clinical coronary disease, peripheral arterial disease, or both. All 331 individuals were unrelated Caucasians of Danish ancestry. There were no significant differences (p greater than 0.05) in genotype distribution or allele frequencies between atherosclerotic and nonatherosclerotic individuals, but in the 85-year-olds, there was evidence (p less than 0.10) for a lower U-allele frequency in nonatherosclerotic women compared to atherosclerotic women. In nonatherosclerotic women, there was a significant decrease in U-allele frequency with age (60 to 85 years). This decrease does not prove conclusively, but is compatible with, the hypothesis that the U-allele predisposes to, or the L-allele protects against, atherosclerosis. The possible effect of the U-allele on the development of atherosclerosis does not seem to be mediated through conventional risk factors. PMID- 2188640 TI - Roles of calcium, cyclic nucleotides, and protein kinase C in regulation of endothelial permeability. AB - We studied the effects of calcium, cyclic nucleotides, and protein kinase C on albumin transfer, electrical resistance, and cytoskeletal actin filaments in cultured human umbilical vein endothelial cells. The endothelial monolayer grown on collagen-treated filters markedly restricted the transfer of albumin relative to its transfer across the filter alone. Both Ca++ ionophore A23187 and ethyleneglycol tetraacetic acid disrupted the integrity of the endothelial monolayer, thereby increasing endothelial albumin transfer and decreasing electrical resistance in a concentration-dependent manner. Neither W-7, a calmodulin antagonist, nor TMB-8, an intracellular Ca++ antagonist, influenced endothelial permeability. In contrast, increases in intracellular cyclic adenosine 5'-monophosphate (AMP) and/or cyclic guanosine 5'-monophosphate (GMP) induced by dibutyryl cyclic AMP, forskolin, 3-isobutyl-1-methylxanthine, 8-bromo cyclic GMP, dibutyryl cyclic GMP, or sodium nitroprusside significantly elevated endothelial electrical resistance and inhibited albumin transfer; similar effects resulted from activation of protein kinase C by phorbol-12-myristate-13-acetate or 1-oleoyl-2-acetyl-glycerol. These substances ruffled the dense peripheral bands of F-actin without compromising the integrity of endothelial monolayer. These results suggest that calcium, cyclic nucleotides, and protein kinase C play important roles in the regulation of endothelial permeability and the maintenance of endothelial integrity. PMID- 2188641 TI - Association of fasting insulin with blood pressure and lipids in young adults. The CARDIA study. AB - The association of insulin with cardiovascular disease (CVD) may be mediated in part by the associations of insulin with CVD risk factors, particularly blood pressure and serum lipids. These associations were examined in 4576 black and white young adults in the CARDIA Study. Fasting insulin level was correlated in univariate analysis with systolic blood pressure (r = 0.16), diastolic blood pressure (r = 0.13), triglycerides (r = 0.27), total cholesterol (r = 0.10), high density lipoprotein (HDL) cholesterol (r = -0.25), and low density lipoprotein (LDL) cholesterol (r = 0.14), and with age, sex, race, glucose, body mass index, alcohol intake, cigarette use, physical activity, and treadmill duration (all p less than 0.0001). After adjustment for these covariates, insulin remained positively associated with blood pressure, triglycerides, total and LDL cholesterol, and apolipoprotein B and was negatively associated with HDL, HDL2 and HDL3 cholesterol, and apolipoprotein A-I in all four race-sex groups. Higher levels of fasting insulin are associated with unfavorable levels of CVD risk factors in young adults; these associations, though relatively small, can be expected to increase the risk of atherosclerosis. Demonstration of these relationships in a large, racially diverse, healthy population suggests that insulin may be an important intermediate risk factor for CVD in a broad segment of the U.S. population. PMID- 2188642 TI - Autoreactive platelet antibody in post transfusion purpura. AB - Post transfusion purpura in a DR3, DRw52 positive, PlA1 negative woman rapidly responded to high-dose intravenous gammaglobulin therapy. Using the platelet immunofluorescence test (PIFT) high titre IgG and IgM alloantibodies were detected in the patient's acute serum. These alloantibodies had PlA1 specificity and the patient's serum produced a broad, 100 kDa band on Western Blot with PlA1 positive platelets. Acute phase serum also contained an IgG antibody which reacted in the PIFT with the patient's own platelets, and PlA1 negative platelets. When tested by Western Blot with PlA1 negative and Glanzmann's Thrombasthenia platelets, the acute serum produced bands at 180 and 200 kDa. The autoreactive antibody was not detected once the platelet count returned to normal. These findings provide evidence for the hypothesis that the mechanism of autologous platelet destruction in PTP is autoimmune. PMID- 2188643 TI - Chest physiotherapy for the medical patient--are current practices effective? PMID- 2188644 TI - Serum antibody response to Mycoplasma hyopneumoniae measured by enzyme-linked immunosorbent assay after experimental and natural infection of pigs. AB - Studies were conducted under experimental and field conditions to determine the effect of infection with M. hyopneumoniae on the immune response in serum as measured by ELISA. Following intratracheal challenge or contact exposure, serologically negative pigs derived from mycoplasma-free piggeries developed an immune response within 10 days. This response continued to rise for a further 50 days. In a field study in a commercial piggery, no animals (0/44) were observed to have M. hyopneumoniae antibodies at day 86 of life. However between day 86 and day 144, 97.7% (42/43) animals sero-converted. These results are discussed in terms of infection spread, particularly in the grower/finisher shed. PMID- 2188645 TI - Isozyme polymorphism of endo-beta-1,4-glucanase in Aspergillus nidulans. AB - An electrophoretic survey of the natural populations of Aspergillus nidulans, the A. nidulans group, and various species belonging to the genus Aspergillus from diverse geographical areas of India was carried out to determine the isozyme polymorphism of endoglucanase. The data revealed the presence of three forms of endoglucanase designated EG I, EG II, and EG III. In some isolates, EG I and EG II were present separately; in others, instead of two separate bands, one thick band was detected, which was designated EG I. In natural isolates of A. nidulans and the A. nidulans group, EG III was detected in most, but not all, isolates, while EG I and EG II were always present. However, in various other species of the genus Aspergillus, EG II was totally lacking. In all the populations at the EG I and EG II region, seven electrophoretic variants each were detected, and at the EG III region four variants were seen. The data suggest that there may be two structural genes for endoglucanase, one coding for proteins in the EG I/EG II zone and another for protein in the EG III zone. PMID- 2188647 TI - Botulinum type F neurotoxin. Large-scale purification and characterization of its binding to rat cerebrocortical synaptosomes. AB - 1. A large-scale purification procedure has been developed for Clostridium botulinum type F neurotoxin. Commencing with 160 litres of bacterial culture, 101 mg of purified type F neurotoxin with a specific toxicity of 2 x 10(7) mouse LD50 (median lethal dose).mg-1 were obtained. 2. Purified type F neurotoxin was labelled to high specific radioactivity (900-1360 Ci/mmol) without loss of biological activity using a chloramine-T procedure. Of the two neurotoxin subunits, the heavy chain was preferentially radiolabelled. 3. Radiolabelled type F neurotoxin displayed specific saturable binding to rat synaptosomes. At least two pools of acceptors were evident: a low content of high-affinity acceptors sites [KD approximately 0.15 nM; Bmax (maximal binding) 20 fmol/mg] and a larger pool of lower-affinity sites (KD greater than 20 nM; Bmax greater than 700 fmol/mg). Both pools of acceptors were sensitive to trypsin and neuraminidase treatment, which suggests that protein and sialic acid residues are components of the synaptosomal acceptors. 4. Experiments investigating competition among botulinum neurotoxin types A, B, E and F for acceptors on rat brain synaptosomes showed that type F neurotoxin binds to acceptor molecules which are completely distinct from those of the other three neurotoxins. PMID- 2188648 TI - Immunological localization of ribosomes in striated rat muscle. Evidence for myofibrillar association and ontological changes in the subsarcolemmal:myofibrillar distribution. AB - Ribosome distribution in skeletal-muscle fibres was investigated immunohistochemically by using polyclonal antibodies raised against large ribosomal-subunit proteins isolated from rat liver. Immunoblot analysis showed the antibodies to recognize five major proteins of the large subunit; these were identified as L4, L6, L7, L15 and L17 by two-dimensional electrophoresis. Immunohistochemistry of frozen rat skeletal-muscle sections showed staining of both the subsarcolemmal and intermyofibrillar cytoplasm. A distinct banding pattern was observed, and when peroxidase and phase-contrast images of the same field were compared by image analysis the anti-ribosome staining was found to correspond to the A-bands. These results suggest that a proportion of muscle ribosomes are present in the myofibrillar cytoplasm in a regular fashion, possibly associated with myosin. Densitometric analysis of the peroxidase immunostaining showed that the ratio of myofibrillar to sub-sarcolemmal ribosomal material was lower in muscle from 51-day-old rats compared with those from 14-day old animals. PMID- 2188646 TI - Assembly and secretion of hepatic very-low-density lipoprotein. AB - In contrast to water-soluble fuels such as glucose or ketone bodies, the use of lipids as an energy source for tissues has required the development of complex structures for their transport through the aqueous plasma. In the case of endogenously synthesized triacylglycerol this is achieved by the assembly and secretion of hepatic VLDL which provides the necessary stability in an aqueous medium. An essential component of this assembly process is apo B. Dietary changes which require an increase in hepatic VLDL secretion appear to be accompanied by increases in the availability of functional apo B. Interesting questions relate to: (a) the intracellular site(s) of triacylglycerol association with apo B, and (b) the mechanism(s) by which the availability of functional apo B at this site responds to metabolic and hormonal signals which reflect dietary status and, thus, the need to secrete triacylglycerol. As regards the latter, although in some cases changes in apo B synthesis occur in response to VLDL secretion hepatic apo B mRNA levels appear to be quite stable in vitro. Intracellular switching of apo B between the secretory and degradative pathways may be important in controlling VLDL assembly and post-translational modifications of the apoprotein may also play a role by influencing its ability to bind to triacylglycerol. Transport is not the only problem associated with the utilization of a concentrated energy source such as triacylglycerol and the complex problems of waste product disposal and recycling have to be dealt with. In the case of triacylglycerol, potentially toxic waste products include atherogenic remnants and LDL. The overall problem, then, in the long-term, involves the development of a 'safe' means of utilizing triacylglycerol and this requirement accounts for much of the complexity of plasma lipoprotein metabolism. In this area, the rat could teach the human a few tricks. One of these appears to be the utilization of hepatic apo B48 rather than apo B100 for VLDL assembly in response to increases in the extrahepatic utilization of hepatically synthesized triacylglycerol. Under these conditions, the remnants of hepatic triacylglycerol utilization by peripheral tissues are cleared from the plasma much more readily via a process which seems to involve the cycling of more triacylglycerol back to the liver than that which occurs in humans. The means by which this is achieved, though, are obscure and may involve a chylomicron remnant receptor, the nature of which, itself, remains controversial.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2188649 TI - Inhibition of pyruvate:ferredoxin oxidoreductase from Trichomonas vaginalis by pyruvate and its analogues. Comparison with the pyruvate decarboxylase component of the pyruvate dehydrogenase complex. AB - Pyruvate:ferredoxin oxidoreductase and the pyruvate dehydrogenase multi-enzyme complex both catalyse the CoA-dependent oxidative decarboxylation of pyruvate but differ in size, subunit composition and mechanism. Comparison of the pyruvate:ferredoxin oxidoreductase from the protozoon Trichomonas vaginalis and the pyruvate dehydrogenase component of the Escherichia coli pyruvate dehydrogenase complex shows that both are inactivated by incubation with pyruvate under aerobic conditions in the absence of co-substrates. However, only the former is irreversibly inhibited by incubation with hydroxypyruvate, and only the latter by incubation with bromopyruvate. Pyruvate:ferredoxin oxidoreductase activity is potently, but reversibly, inhibited by addition of bromopyruvate in the presence of CoA, and it is suggested that the mechanism involves formation of an adduct between CoA and bromopyruvate in the active site of the enzyme. It is proposed that both enzymes are inactivated by pyruvate through a mechanism involving oxidation of an enzyme-bound thiamin pyrophosphate/substrate adduct to form a tightly bound inhibitory species, possibly thiamin thiazolone pyrophosphate as hypothesized by Sumegi & Alkonyi. PMID- 2188651 TI - Cell polarity and development of the first epithelium. AB - In the 4 1/2 to 5 days between fertilization and implantation, the mouse conceptus must gain the abilities to implant and produce an embryo. Each of these is the sole developmental responsibility of one of two cell types forming the blastocyst, trophectoderm and inner cell mass (ICM), respectively. Trophectoderm is a polarized transporting epithelium while the ICM is an aggregate of non epithelial pluripotent stem cells. These two cell types originate from the division of polar blastomeres when their cleavage furrows parallel their apical surfaces. Blastomeres polarize in response to asymmetric cell--cell contact, and understanding the mechanism of this induction is regarded as the key to understanding the origin of trophectoderm and ICM. Here we propose a model based on transcellular ion current loops for the induction of cell polarity during the development of the first epithelium, trophectoderm. PMID- 2188652 TI - The regulation of DNA repair during development. AB - DNA repair is important in such phenomena as carcinogenesis and aging. While much is known about DNA repair in single-cell systems such as bacteria, yeast, and cultured mammalian cells, it is necessary to examine DNA repair in a developmental context in order to completely understand its processes in complex metazoa such as man. We present data to support the notion that proliferating cells from organ systems, tumors, and embryos have a greater DNA repair capacity than terminally differentiated, nonproliferating cells. Differential expression of repair genes and accessibility of chromatin to repair enzymes are considered as determinants in the developmental regulation of DNA repair. PMID- 2188650 TI - Pyruvate dehydrogenase activities and rates of lipogenesis during the fed-to starved transition in liver and brown adipose tissue of the rat. AB - The percentages of pyruvate dehydrogenase complex (PDH) in the active form (PDHa) in two lipogenic tissues (liver and brown adipose tissue) in the fed state were 12.0% and 13.4% respectively. After acute (0.5 h) insulin treatment, PDHa activities had increased by 77% in liver and by 234% in brown fat. Significant decreases in PDHa activities were observed in both tissues by 5 h after the removal of food. The patterns of decline in PDHa activities in the two lipogenic tissues were similar in that the major decreases in activities were observed within the first 7 h of starvation. The significant decreases in PDHa activities observed after starvation for 6 h were accompanied by decreased rates of lipogenesis. Hepatic and brown-fat PDHa activities after acute (30 min) exposure to exogenous insulin were less in 6 h-starved than in fed rats, but the absolute increases in PDHa activities over the 30 min exposure period were similar in fed and 6 h-starved rats. Increases in PDHa activities were paralleled by increases in lipid synthesis in both tissues. Re-activation of PDH in response to insulin treatment or chow re-feeding after 48 h starvation occurred more rapidly in brown adipose tissue than in liver. The results are discussed in relation to the importance of the activity of the PDH complex as a determinant of the total rate of lipogenesis during the fed-to-starved transition and after insulin challenge or re-feeding. PMID- 2188654 TI - The organization of replication centres in higher eukaryotes. PMID- 2188653 TI - Regulation of cell-type-specific transcription and differentiation of the pituitary. AB - The transcription of rat prolactin and growth hormone genes in vitro requires a pituitary transcription factor, specific to certain cell types in the pituitary, which currently appears to be the PUF-I/Pit-1/GHF-1 protein. This factor binds to cis-regulatory elements in the 5' region of both genes and exerts a positive influence on transcription initiation presumably by interacting with general transcription factors. The PUF-I/Pit-1/GHF-1 transcriptional regulatory protein probably has an important role in not only the differentiation of the pituitary lactotroph/somatotroph cell lineage; it is also expressed in the early development of the nervous system but its function there is less well documented. It appears to be one member of a family of trans-activator proteins involved in differential gene expression in several cell types. PMID- 2188655 TI - Comprehensive computerized 2D gel protein databases offer a global approach to the study of the mammalian cell. PMID- 2188657 TI - Tryptophan promoter derivatives on multicopy plasmids: a comparative analysis of expression potentials in Escherichia coli. AB - A collection of variant plasmids expressing either Escherichia coli galactokinase or human serum albumin under the control of several E. coli trp promoter derivatives were constructed and studied for both efficiency of expression and regulation by tryptophan. Several variables, including the length of the upstream region, tandem duplications of a core promoter, and the insertion of the trp repressor trpR gene onto the expression vector, were studied. It is shown that derivatives containing sequences upstream from the -35 region or multiple copies of the trp promoter produce twofold higher levels of protein than plasmids with a minimal trp promoter truncated at -40. We show that the expression of a heterologous protein such as albumin can be significantly improved (13% vs. 7% of total proteins) if both the upstream trp promoter region, which enhances promoter strength, and an intact trpR gene, are included on the plasmids. PMID- 2188656 TI - Expression of alcohol-inducible rabbit liver cytochrome P-450 3a (P-450IIE1) in Saccharomyces cerevisiae with the copper-inducible CUP1 promoter. AB - The expression of the cDNA for alcohol-inducible rabbit liver microsomal cytochrome P-450 form 3a (P450IIE1) in Saccharomyces cerevisiae, with the use of the copper-inducible yeast metallothionein (CUP1) promoter and the ADH1 promoter, is described. Strains 50.L4 and PP1002 were compared for optimal levels of expressed protein. Immunoblot analysis showed that a much higher level of expression of cytochrome P-450 3a is obtained with strain 50.L4, and that the uninduced levels of expressed protein are similar with the two promoters. With the CUP1 promoter, transcription of the cDNA is strongly induced in the presence of cupric ions, and the amount of immunoreactive protein expressed in increased 20-fold in strain 50.L4, such that it constitutes 0.8% of the total cellular protein. The cytochrome P-450 holoenzyme content of these cells, calculated from the reduced CO difference spectrum, is about 0.02 nmole/mg of protein, or 0.1% of the total cellular protein. The holoenzyme content of microsomes prepared from these cells is up to 0.06 nmole/mg of protein, or 0.4% of the microsomal protein. Microsomal assays for ethylene formation from N-nitrosodiethylamine and for aniline p-hydroxylation, two reactions typical of purified rabbit cytochrome P 450 form 3a, showed that the cytochrome synthesized in yeast catalyzes both reactions. Furthermore, polyclonal anti-3a IgG completely inhibits the reactions with both substrates in yeast microsomes. A comparison of the product ratios from these substrates showed that the cytochrome P-450 3a expressed in yeast has catalytic activities similar to those of the authentic rabbit protein. PMID- 2188658 TI - Crystallographic studies of carbohydrates. AB - The monosaccharides which constitute the monomer units of many important industrial and biological macromolecules are well represented among the 2000 crystal structures of the carbohydrate class 45 of the Cambridge Structural Database. There are few examples of crystal structure analyses of the corresponding acids, but many of their calcium salts and calcium salt complexes. With the exception of the disaccharides and cyclodextrins, the oligosaccharides are not well represented, with less than ten trisaccharides, one tetrasaccharide and one hexasaccharide-iodide complex. Two important conformational factors are the Hassel-Ottar effect and the anomeric effect, both of which have been studied using crystallographic data. Hydrogen bonding is ubiquitous in carbohydrate crystals and generally involves all the hydroxyls as both donors and acceptors, and some of the ring and glycosidic oxygens as acceptors. These hydrogen bonds tend to form finite or infinite chains. In hydrates, these chains are linked through the water molecules to form networks. Cyclic hydrogen-bond systems are observed in the cyclodextrins. Long-chain alkylated carbohydrates provide a large class of thermotropic and lyotropic liquid crystals, and some non-ionic surfactants which have been shown to be useful for membrane-protein solubilization and crystallization. PMID- 2188659 TI - From protein synthesis to antibody formation and cellular immunity: a personal view. PMID- 2188660 TI - Regulation of hemopoiesis by bone marrow stromal cells and their products. PMID- 2188661 TI - Genetic and mutational analysis of the T-cell antigen receptor. AB - The studies reviewed here exploit the fact that the TCR is a multisubunit complex whose perturbation initiates an assortment of biochemical pathways and diverse biological responses. The creation and analysis of T cells bearing aberrant TCRs has led to a number of important conclusions and provided a framework for some educated speculation about T-cell biology. The assembly of the TCR is a highly regulated process in which the majority of the synthesized material is rapidly degraded. Partial complexes, which potentially might interfere with ligand binding by, or the function of, complete receptor molecules, are not tolerated; this "architectural editing" is performed in a compartment(s) associated with the ER or, in some cases, lysosomes. The individual chains of the TCR can be separated into subgroups that are, perhaps, functionally autonomous. The disulfide-linked variable chains bind ligand. The zeta eta heterodimer appears to be largely responsible for coupling receptor occupancy to PI hydrolysis, the zeta 2 heterodimer may couple to tyrosine kinase activation and/or other signaling pathways. The zeta 2-containing receptors are fully capable of transducing signals leading to IL-2 production and growth inhibition, while the presence of the zeta eta heterodimer is associated with the autolytic response of T-cell hybridomas to activation. Finally, an intact and functional TCR must be present for optimal expression of some, although not all, manifestations of activation that are initiated via independent cell-surface molecules such as Thy-1, Ly-6, and CD2. Future experiments in which TCR chains that incorporate site-directed mutations are transfected into T and non-T cells are certain to enhance our appreciation of how the structure of this receptor determines its many biological attributes. PMID- 2188662 TI - Role of mononuclear phagocytes in the pathogenesis of human immunodeficiency virus infection. AB - We have presented evidence in this review for the following: (a) Macrophages are likely the first cell infected by HIV. Recovery of HIV from macrophages has been documented in the early stages of infection in which virus isolation in T cells is unsuccessful and detectable levels of antibodies against HIV are absent. (b) Macrophages are major reservoirs for HIV during all stages of infection. Unlike the lytic infection of T cells, HIV-infected macrophages show little or no virus induced cytopathic effects. HIV-infected macrophages persist in tissue for extended periods of time (months) with large numbers of infectious particles contained within intracytoplasmic vacuoles. (c) Macrophages are a vector for the spread of infection to different tissues within the patient and between individuals. Several studies suggest a "Trojan horse" role for HIV-infected macrophages in the dissemination of infectious particles. The predominant cell in most bodily fluids (alveolar fluid, colostrum, semen, vaginal secretions) is the macrophage. In semen, for example, the numbers of macrophages exceed those of lymphocytes by more than 20-fold. (d) Macrophages are major regulatory cells that control the pace and intensity of disease progression in HIV infection. Macrophage secretory products are implicated in the pathogenesis of CNS disease and in control of viral latency in HIV-infected T cells. This litany of events in which macrophages participate in HIV-infection in humans parallels similar observations in such animal lentivirus infections as visna-maedi or caprine arthritis-encephalitis viruses. HIV interacts with monocytes differently than with T cells. Understanding this interaction may more clearly define both the pathogenesis of HIV disease and strategies for therapeutic intervention. PMID- 2188663 TI - Evolution of class-I MHC genes and proteins: from natural selection to thymic selection. PMID- 2188664 TI - Interleukin-6: an overview. PMID- 2188665 TI - Perforin-mediated target cell lysis by cytolytic T lymphocytes. PMID- 2188666 TI - Catalytic antibodies. PMID- 2188667 TI - VLA proteins in the integrin family: structures, functions, and their role on leukocytes. PMID- 2188668 TI - Stress proteins and immunology. PMID- 2188669 TI - Transmission of signals from the T lymphocyte antigen receptor to the genes responsible for cell proliferation and immune function: the missing link. PMID- 2188670 TI - Regulation of HIV-1 gene expression. PMID- 2188671 TI - Host genetic control of spontaneous and induced immunity to Friend murine retrovirus infection. PMID- 2188672 TI - Molecules related to class-I major histocompatibility complex antigens. PMID- 2188673 TI - Developmental biology of T cells in T cell-receptor transgenic mice. PMID- 2188674 TI - The simian immunodeficiency viruses. PMID- 2188675 TI - The T lymphocyte in experimental allergic encephalomyelitis. PMID- 2188676 TI - Type-I diabetes: a chronic autoimmune disease of human, mouse, and rat. PMID- 2188677 TI - Immunoglobulin class switching: molecular and cellular analysis. PMID- 2188678 TI - Structural basis of immune recognition of influenza virus hemagglutinin. PMID- 2188679 TI - Receptor-mediated antigen uptake and its effect on antigen presentation to class II-restricted T lymphocytes. PMID- 2188680 TI - Cellular and genetic aspects of antigenic variation in trypanosomes. PMID- 2188681 TI - Drug and metabolite-induced perturbations in nuclear structure and function: a review. AB - Clarification of large-scale organization in cell nuclei is central to a full understanding of the mechanisms which underlie replication, transcription, and interaction with the cytoplasmic compartment. Many drugs and natural biological agents affect such processes directly, through inhibitory or stimulatory action, and often reveal structural and functional aspects in nuclei not otherwise apparent. There is increasing evidence that the pore complex - lamina of the nuclear matrix is a primary structural element during interphase, which is pivotal to most nuclear processes. This communication reviews evidence based on studies with drugs, inhibitors, and natural biological processes, that the nuclear matrix concept is indeed valid. It is further shown that despite diversity in mode of action and affected target cells, many compounds induce related or complementary changes in nuclei and that such uniformity in pattern is attributable to the nuclear matrix. A general model of the functional organization of the nucleus is presented, to account for the perturbations observed after mass interference with either transcription, replication, or protein synthesis. PMID- 2188682 TI - Role of acid proteases in brown adipose tissue atrophy caused by fasting in mice. AB - The lysosomal proteolytic capacity of mouse brown adipose tissue (BAT) and its role during fasting were evaluated. The specific activities of acid phosphatase and cathepsins B, D, H, and L were measured in BAT of mice acclimated at 33, 21, and 4 degrees C and in BAT undergoing different rates of protein loss during a 24 to 48-h fast. The specific activities of lysosomal proteases in BAT did not vary with the acclimation status of the animals. Mice acclimated at 33 degrees C showed no significant atrophy of BAT after a fast. In mice kept at 21 degrees C, protein loss from BAT was observed after a fast without change in tissue DNA content. Protein loss from BAT was partially reduced by injection of the acidotropic agent chloroquine. Furthermore, tyrosine release from BAT during fasting was also reduced by injections of chloroquine or leupeptin, a thiol protease inhibitor. Tyrosine release from BAT was maximum within 24 h and returned to prefast values by 36 h, suggesting rapid activation followed by inhibition of the tissue proteolytic activity. However, there was no change in acid protease specific activities, suggesting that these enzymes were not limiting for protein degradation. When cold-acclimated mice were fasted at 21 degrees C, BAT protein loss was markedly enhanced and increases in cathepsin D and L activities were observed, but there was no change in cathepsin B and H and acid phosphatase specific activities. These results indicate that BAT contains an important lysosomal proteolytic pathway that is involved in the rapid reduction of the tissue thermogenic capacity during a fast. PMID- 2188683 TI - Glucose uptake in human and animal muscle cells in culture. AB - Human muscle cells were grown in culture from satellite cells present in muscle biopsies and fusion-competent clones were identified. Hexose uptake was studied in fused myotubes of human muscle cells in culture and compared with hexose uptake in myotubes of the rat L6 and mouse C2C12 muscle cell lines. Uptake of 2 deoxyglucose was saturable and showed an apparent Km of about 1.5 mM in myotubes of all three cell types. The Vmax of uptake was about 6000 pmol/(min.mg protein) in human cells, 4000 pmol/(min.mg protein) in mouse C2C12 muscle cells, and 500 pmol/(min.mg protein) in L6 cells. Hexose uptake was inhibited approximately 90% by cytochalasin B in human, rat, and mouse muscle cell cultures. Insulin stimulated 2-deoxyglucose uptake in all three cultures. The hormone also stimulated transport of 3-O-methylglucose. The sensitivity to insulin was higher in human and C2C12 mouse myotubes (half-maximal stimulation observed at 3.5 X 10( 9) M) than in rat L6 myotubes (half-maximal stimulation observed at 2.5 X 10(-8) M). However, insulin (10(-6) M) stimulated hexose uptake to a larger extent (2.37 fold) in L6 than in either human (1.58-fold) or mouse (1.39-fold) myotubes. It is concluded that human muscle cells grown in culture display carrier-mediated glucose uptake, with qualitatively similar characteristics to those of other muscle cells, and that insulin stimulates hexose uptake in human cells. These cultures will be instrumental in the study of human insulin resistance and in investigations on the mechanism of action of antidiabetic drugs. PMID- 2188684 TI - Expression of mature pulmonary surfactant-associated protein B (SP-B) in Escherichia coli using truncated human SP-B cDNAs. AB - The present communication documents attempts to produce the mature form of human surfactant-associated protein B (SP-B) by modification of the 5' and 3' regions of the cDNA and expression of the truncated cDNAs after insertion into the vector pKK223-3. The 5' end of a cDNA for human SP-B (1407 base pairs) was reconstructed through the ligation of synthetic oligonucleotides to an internal PstI site in the 5' region. This construction coded for the initiation of protein synthesis at a Met codon adjacent to a codon for the N-terminal Phe of the mature polypeptide. Variable amounts of the 3' end of the human SP-B cDNA were deleted with mung bean nuclease and exonuclease III. The resulting blunt-ended 3' fragments were then ligated to a synthetic oligonucleotide linker designed to create a stop codon. The modified 5' and 3' ends were ligated to a short PstI-BamHI fragment isolated from the SP-B cDNA and inserted into the expression vector pKK223-3. In vitro translation of sense mRNAs derived from the truncated SP-B cDNAs yielded oligopeptides of appropriate molecular weights, as indicated by urea - sodium dodecyl sulphate - polyacrylamide gel electrophoresis of either intact or immunoprecipitated reaction mixtures. Expression of SP-B in Escherichia coli was confirmed by Northern blot analysis for the mRNAs corresponding to the truncated cDNAs in appropriately transformed bacteria induced with the galactose analog isopropyl-beta-thiogalactoside. Western blot analysis using rabbit antisera prepared against bovine SP-B confirmed the presence of mature SP-B in lipid extracts of transformed E. coli, but the amounts were very small.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188685 TI - Which antihypertensive? PMID- 2188686 TI - Clinical allergy--state of the art. PMID- 2188687 TI - Statistical distribution of hydrophobic residues along the length of protein chains. Implications for protein folding and evolution. AB - We consider in this paper the statistical distribution of hydrophobic residues along the length of protein chains. For this purpose we used a binary hydrophobicity scale which assigns hydrophobic residues a value of one and non hydrophobes a value of zero. The resulting binary sequences are tested for randomness using the standard run test. For the majority of the 5,247 proteins examined, the distribution of hydrophobic residues along a sequence cannot be distinguished from that expected for a random distribution. This suggests that (a) functional proteins may have originated from random sequences, (b) the folding of proteins into compact structures may be much more permissive with less sequence specificity than previously thought, and (c) the clusters of hydrophobic residues along chains which are revealed by hydrophobicity plots are a natural consequence of a random distribution and can be conveniently described by binomial statistics. PMID- 2188688 TI - Rapid toxicity testing based on yeast respiratory activity. PMID- 2188689 TI - Activation of chemical promutagens by Selenastrum capricornutum in the plant cell/microbe coincubation assay. PMID- 2188690 TI - Aids to prevent pressure sores. PMID- 2188691 TI - Single domain antibodies. PMID- 2188692 TI - Minitracheotomy. PMID- 2188693 TI - The toxic shock syndrome. PMID- 2188694 TI - Kawasaki syndrome: lessons for Britain. PMID- 2188695 TI - Adolescent sexuality. PMID- 2188696 TI - Randomised controlled trial of day patient versus inpatient psychiatric treatment. AB - OBJECTIVE: To assess the proportion of acutely ill psychiatric patients who can be treated in a day hospital and compare the outcome of day patient and inpatient treatment. DESIGN: Prospective randomised controlled trial of day patient versus inpatient treatment after exclusion of patients precluded by severity of illness or other factors from being treated as day patients. All three groups assessed at three and 12 months. SETTING: Teaching hospital serving small socially deprived inner city area. Day hospital designed to take acute admissions because of few beds. PATIENTS: 175 Patients were considered, of whom 73 could not be allocated. Of the remaining 102 patients, 51 were allocated to each treatment setting but only 89 became established in treatment--namely, 41 day patients and 48 inpatients. 73 Of these 89 patients were reassessed at three months and 70 at one year. INTERVENTIONS: Standard day patient and inpatient treatment. MAIN OUTCOME MEASURES: Discharge from hospital and return to previous level of social functioning; reduction of psychiatric symptoms, abnormal behaviour, and burden on relatives. RESULTS: 33 Of 48 inpatients were discharged at three months compared with 17 of 41 day patients. But at one year 9 of 48 inpatients and three of 41 day patients were in hospital. 18 Of 35 day patients and 16 of 39 inpatients were at their previous level of social functioning at one year. The only significant difference at three months was a greater improvement in social role performance in the inpatients. At one year there was no significant difference between day patients and inpatients in present state examination summary scores and social role performance, burden, or behaviour. CONCLUSIONS: Roughly 40% of all acutely ill patients presenting for admission to a psychiatric unit may be treated satisfactorily in a well staffed day hospital. The outcome of treatment is similar to that of inpatient care but might possibly reduce readmissions. The hospital costs seem to be similar but further research is required to assess the costs in terms of extra demands on relatives, general practitioners, and other community resources. PMID- 2188697 TI - Is intrauterine growth retardation with normal umbilical artery blood flow a benign condition? AB - OBJECTIVE: To determine whether intrauterine growth retardation associated with normal umbilical artery blood flow is a benign condition. DESIGN: A prospective comparative study of growth retarded fetuses with normal and abnormal umbilical artery blood flow. SETTING: The fetal assessment clinic of a large maternity hospital in Ireland. PATIENTS: 179 Women with singleton pregnancies in which the fetal abdominal circumference, measured by ultrasonography, was below the fifth centile for gestation. MAIN OUTCOME MEASURES: Perinatal deaths, fetal distress requiring caesarean section, preterm delivery, cerebral irritation. RESULTS: Of 124 fetuses with normal flow, all physically normal fetuses survived but one baby had cerebral irritation; there were six preterm deliveries and four caesarean sections for fetal distress. Among 55 women with abnormal flow there were two midtrimester abortions, three perinatal deaths, and one case of cerebral irritation in physically normal fetuses. CONCLUSIONS: Intrauterine growth retardation associated with normal umbilical blood flow is a different entity from that associated with abnormal flow, normal flow being largely benign and abnormal flow carrying a serious risk of adverse outcome. PMID- 2188699 TI - Pelvic inflammatory disease. PMID- 2188700 TI - Maternal and fetal screening for antenatal care. PMID- 2188698 TI - Calcium supplementation of the diet: justified by present evidence. PMID- 2188701 TI - Radioactive substances decontamination exercise. PMID- 2188702 TI - Henrik Ibsen's An Enemy of the People and Eduard Meissner's expulsion from Teplitz. PMID- 2188703 TI - Federal efforts at reducing health care costs: the effect on technology. Interview by Michael J. Miller. PMID- 2188704 TI - Understanding techniques for measuring cardiac output. AB - In summary, use of thermodilution as a method to measure cardiac output has attained universal appeal in the clinical environment. Other means of detecting cardiac output (impedance-cardiogram and ballistocardiogram, to name two) have been developed and are being used clinically, but the development of the flow directed thermodilution catheter has profoundly affected the universal acceptance of the thermodilution method. Thermodilution techniques, when performed properly, are capable of obtaining accurate and reproducible results. Medical and nursing personnel who are educated in proper procedures will be able to make educated choices when faced with difficult decisions. It is likely that they will turn to the biomedical or clinical engineering department for help if those personnel are well informed regarding the techniques and procedures. PMID- 2188705 TI - Pain problems in the ICU. AB - To manage pain in an ICU setting effectively, one must first understand the unique features associated with the disease process for which patients are admitted. Although there are certain common denominators, a postoperative patient is different from a patient with an acute myocardial infarction. This article reviews the aspects of pain associated with the individual syndromes of patients admitted to an ICU. PMID- 2188706 TI - Monitoring pain control and charting. AB - This article discusses the roles of the critical care team in providing pain relief. The attitudes of the staff concerning pain relief impact on the delivery of care. Assessment tools, computer systems, and flow sheets to assist in charting are described. Nurses have a role in use of epidural administration of narcotics, and provide relief with the use of patient-controlled analgesia and general pain relief measures. Pain as a nursing diagnosis, substance abuse in the medical profession, and control of narcotics are also issues discussed. PMID- 2188707 TI - Intravenous narcotics in the ICU. AB - In summary, there are now available very potent narcotics, with small side effect liability. Critical care physicians should be experts in administration of intravenous narcotics and should understand the concepts behind different methods of administration. Much more patient satisfaction and safety can be obtained if as much attention is paid to how a drug is administered as to its pharmacologic actions. Intravenous administration allows rapid and almost complete control of desired effect. Intravenous access is universally available in the ICU population, and we should take every advantage of it. PMID- 2188708 TI - Epidural opioid analgesia. AB - Epidural opioid analgesia has become an important therapeutic technique in the management of acute pain and has been demonstrated to be superior or equal to other parenteral opioid techniques (intramuscular, intravenous, PCA) with less associated sedation and significantly smaller doses of drugs. Beneficial therapeutic effects of epidural opioids as a result of improved analgesia include improvement in pulmonary function, modification of the endocrine-metabolic stress response, improvement in time to ambulation, decreased morbidity, and shorter hospital stay. The epidural administration of opioids is associated with potential side effects and complications, the most serious potential side effect being that of respiratory depression. This, as well as most of the other potential medication-related side effects associated with epidural opioid analgesia, is for the most part also associated with opioid analgesia provided by other routes of administration. These potential problems either occur rarely, or are controllable or preventable with appropriate patient selection and management. The potential benefits to the critical care patient as a result of the superior analgesia and reduced systemic effects associated with epidural opioid analgesia represent distinct medical and economic advantages, compared to conventional analgesic techniques. PMID- 2188709 TI - Nerve blocks in the critical care environment. AB - The critical care patient population has much to gain from properly administered neural blockade. Effective analgesia alone may make the difference between a patient who is able to compensate for their acute insult and one who cannot. A good example is the patient with multiple fractured ribs, who, after intercostal nerve blocks, no longer requires intubation and mechanical ventilation. The authors believe that effective analgesia is just the beginning of the beneficial effects of neural blockade, because blockade of the afferent limb of sympathetic and sensory nerves may circumvent the neuroendocrine response to acute injury. There is evidence that the stress response is not beneficial in the hospital setting and in fact may be detrimental. Some of the effects include elevated plasma catecholamines, ADH, cortisol, and blood glucose, which contribute to tachycardia, hypertension, increased myocardial work and oxygen consumption, salt and water retention, and a catabolic state with negative nitrogen balance. Whether these changes result in reduced morbidity and mortality has been the subject of several studies, but more studies are needed. It would seem that critically ill patients with little physiologic reserve might be the best population to study because even a small improvement may improve survival. A small beneficial effect in healthy postoperative patients may not be clinically apparent. Most would agree that neural blockade used intraoperatively results in reduced blood loss and a lower incidence of postoperative thromboembolism. The continuation of these techniques into the postoperative period may reduce morbidity and mortality in high-risk patients. A word of caution is in order. The indiscriminate application of the techniques described in this article to critically ill patients would not be in the patients' best interest. Nerve blocks are only safe in the hands of those physicians specifically trained to perform them. In addition, local anesthetics have a low therapeutic ratio, and their administration requires continual observation. The use of epidural or intrathecal opioids alone or in combination with other agents also has potentially serious side effects, and requires continual patient monitoring. The proper performance and maintenance of these techniques requires a large commitment of time, manpower, equipment, and a multidisciplinary approach to include physicians, nursing, and support staff. Nerve blocks and other sophisticated techniques started in the operating room or critical care unit should not necessarily be discontinued when the patient is transferred to a ward bed because the full benefit of this therapy may not have been fully realized.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2188710 TI - Neurologic pain syndromes in patients with cancer. AB - One third of cancer patients in active therapy and two thirds of patients with far-advanced disease have significant pain. A series of specific neurologic pain syndromes occur in this population and are unique to this pain population. Early diagnosis and treatment are critical to prevent irreversible neurologic damage and chronic neuropathic pain. PMID- 2188711 TI - Psychological strategies in acute pain management. AB - Psychological strategies can facilitate management of acute pain. Methods of intervening that are reviewed include information provision, cognitive methods such as self-statements, distraction or attention control, relaxation, and hypnosis. Individual patient coping style and anxiety may moderate need for or ability to use these techniques. Increasing perceived control may be an underlying factor common to all psychological interventions for the management of pain. PMID- 2188712 TI - Pain management following trauma and burns. AB - Effective pain management in trauma patients requires an understanding of both the physiologic responses to injury, and the potential modification of these responses produced by analgesic and anesthetic agents. Complex, multisystem injuries occur frequently and therapeutic intervention for the control of pain must be carefully incorporated within the overall management plan. Pain management strategies for specific injuries are discussed. PMID- 2188713 TI - Non-narcotic modalities for the management of acute pain. AB - The possible options for the management of acute pain are quite numerous and continue to expand as our understanding of the mechanisms of pain becomes increasing sophisticated. Many of the options discussed have been available for years, and their present underutilization may be a reflection of the lack of emphasis on the importance of management of acute pain. An illustration of this would be our present ritual of prescribing narcotics postoperatively, a longstanding, but unfortunately inadequate practice. Because of poor selection and scheduling of doses, postoperative analgesia is typically a less than satisfactory experience for many patients convalescing in a hospital following surgery. The clinician should of course be guided by the clinical situation itself in order to determine what modality or combination of modalities may be appropriate for pain management. Certain techniques, such as continuous local anesthetic infusions, may warrant an escalated level of monitoring and ancillary care. Other techniques, such as the infiltration of a wound with local anesthetic or the addition of a nonsteroidal anti-inflammatory agent to a regimen of mild oral narcotics are so simple that excluding them from patient care is almost callous and inconsiderate. Attention to the mechanisms of pain that may be present in a given situation, whether it be muscle spasm, ischemia, inflammation, edema, or nerve injury, may guide the clinician toward a more rational approach in managing that pain. PMID- 2188714 TI - Stroke in women. AB - In terms of percentage of total deaths, stroke is second and fourth for women and men, respectively, but in terms of potential years of life lost, it is seventh and sixth, respectively. In both women and men, stroke rates have declined. Acetylsalicylic acid has been shown to reduce significantly stroke, death and stroke-related death in men, with no detectable benefit for women. A major hormonal effect appears unlikely to explain the lack of female responsiveness. The risk factors associated with stroke are generally not different in the two sexes. There is evidence that high dose estrogen, hypertension and smoking are important cumulative factors for premenopausal women. The risk of vascular disease is reduced by post menopausal hormone replacement. Pregnancy increases the risk of thrombotic cerebrovascular events, particularly during the second and third trimesters of pregnancy. Heavy drinkers have a fourfold increase and light drinkers a decrease to one-half of relative risk of stroke compared to nondrinkers. Cigarette smoking increases the risk of stroke. Lifestyle may also play a role. PMID- 2188716 TI - Cardiovascular disease in pregnancy. AB - Heart disease is the most important nonobstetric cause of maternal death; however, most young women with heart disease do well during pregnancy. If the physician is uncertain of the effects of pregnancy on a particular heart condition, needless restrictions may be imposed. The main hazards are: pulmonary edema when it occurs suddenly in mitral stenosis; pulmonary hypertension (because pulmonary vascular disease tends to be exacerbated by pregnancy); infective endocarditis (this is rare); and fulminating peripartum cardiomyopathy. The practical management of the pregnant patient with various concomitant heart conditions (congenital heart disease, pulmonary hypertension, rheumatic heart disease, anticoagulants and artificial valves, constrictive pericarditis, kyphoscoliosis, Marfan's syndrome, mitral prolapse, hypertrophic cardiomyopathy, dilated cardiomyopathy, infective endocarditis, and arrhythmias) is discussed. An absolute indication for therapeutic abortion is severe pulmonary vascular disease; discretionary indications include 'chronic thromboembolic pulmonary hypertension,' cardiomyopathies (depending on the hemodynamic disturbance), and Marfan's syndrome. PMID- 2188715 TI - Women, lipoproteins and cardiovascular disease risk. AB - Atherosclerosis, lipoprotein structure, lipoprotein metabolism and role in atherogenesis, epidemiology of lipoproteins and coronary artery disease, and current public health guidelines for cholesterol control are described. Low density lipoprotein cholesterol levels rise with age in both men and women. High density lipoprotein (HDL) levels decline after menopause. Special aspects of coronary risk in women include the stronger role of diabetes, hypertriglyceridemia and HDL. In addition, the effects of exogenous hormone therapy, both in the form or oral contraceptives and post menopausal hormone replacement should be considered. Careful attention to these issues may reduce cardiovascular morbidity in adult women. PMID- 2188717 TI - Effects of sex steroid hormones on lipoprotein levels in pre- and post menopausal women. AB - Women are affected by disorders of lipid metabolism in the same way as men. Sex steroids given as oral contraceptives at all doses have clearcut, formulation specific effects on lipoprotein levels in reproductive-aged women. In estrogen dominant versus androgenic progestin-dominant formulations, LDL cholesterol levels were unchanged and significantly increased, respectively, and HDL cholesterol was increased and decreased, respectively. The greatest HDL lowering is seen with the most androgenic formulations. Major increases in LDL cholesterol confer risk for cardiovascular disease on this group, so caution is recommended in formulation selection. In general, cardiovascular disease risk in post menopausal women using estrogen is reduced 30 to 70%. Concurrent administration of progestin with post menopausal estrogen appears to reduce the beneficial rise in HDL associated with estrogen administration alone. Cardiovascular disease is likely to be reduced by estrogen in post menopausal women. PMID- 2188718 TI - Dystocia and cesarean section. PMID- 2188719 TI - Ceftizoxime: a third-generation cephalosporin active against anaerobic bacteria. Committee on Antimicrobial Agents, Canadian Infectious Disease Society. PMID- 2188720 TI - Early detection of depression by primary care physicians. AB - The overall prevalence of depression is from 3.5% to 27%. The burden of suffering is high and includes death through suicide. In most cases treatment is effective, but important episodes of depression are being missed. To determine whether a brief, systematic assessment for the early detection of depression should be part of the periodic health examination we searched MEDLINE and the Science Citation Index for randomized controlled trials that evaluated the effectiveness of early detection of depression with a questionnaire. Seven instruments met our quality criteria; the Beck Depression Inventory, the Center for Epidemiologic Studies Depression Scale, the Zung Self-Assessment Depression Scale, the General Health Questionnaire, the Hopkins Symptom Checklist, the Mental Health Inventory and the Hospital Anxiety and Depression Scale. The four randomized controlled trials failed to provide adequate evidence of the benefit of routine screening. Early detection is difficult because of depression's natural history, the role of symptoms, the cultural diversity of Canada and how detection instruments have been developed. Depression deserves careful attention from primary care physicians; however, further research and development is required before the widespread routine use of any detection test can be recommended. PMID- 2188722 TI - Point mutation at codon 12 of the Ki-ras gene in a primary breast carcinoma and the MDA-MB-134 human mammary carcinoma cell line. AB - We found an activated Kirsten (Ki)-ras gene in the MDA-MB-134 breast carcinoma cell line by transfection of NIH3T3 cells. Oligonucleotide hybridization demonstrated that this cell line carries a single G to C point mutation at position 12 leading to a glycine-arginine substitution. However, only a fraction of the cell population seems to contain this Ki-ras mutation. Since mutations can occur in cell lines during in vitro culture, we searched in breast carcinoma samples for the presence of single mutations at codon 12, but also for the presence of the double mutation previously found in the H-466B breast carcinoma cell line. Using polymerase chain reaction (PCR), we detected one primary tumour carrying a single mutation at codon 12. No double mutation was found in any of the tumours. These results show that Ki-ras gene mutation could be involved in breast carcinogenesis, albeit at a low frequency. PMID- 2188721 TI - Periodic health examination, 1990 update: 2. Early detection of depression and prevention of suicide. Canadian Task Force on the Periodic Health Examination. PMID- 2188723 TI - [Sigmund Freud and modern psychoanalysis]. AB - In September 1989 50 years have elapsed since the death of one of the most distinguished personalities of science and culture in this century, Sigmund Freud. Although born in Pribor in Moravia, he spent most of his productive life in Vienna. He became the founder and pioneer of psychoanalysis--a therapeutic method of neuroses and the remarkable psychological theory which by its emphasis on unconscious, deep underlying psychic processes caused a great advance of knowledge of man of himself. Nowadays psychoanalysis is used in the world not only as a therapeutic method in neuroses, personality disorders and psychosomatic diseases but is developed further as a theoretical and scientific discipline which in many respects exceeds Freud's basic work. Modern psychoanalytic literature was not published in this country in recent decades and thus those interested in it have little opportunity to become familiar with it. Health authorities in advanced countries accept psychoanalysis and thus also in our conditions a place must be sought for psychoanalysis at least in the system of psychiatric and psychotherapeutic care. PMID- 2188724 TI - [Karl Asmund Rudlophi and Jean de Carro]. PMID- 2188725 TI - [A consulting system for insulin therapy in diabetes]. AB - The authors describe a computer system which provides consultations on insulin treatment of diabetes. The intentions and aims of computer consultation and means for their implementation are described. The basic element of the system is the model of insulin pharmacodynamics. Two concepts are used to differentiate individual characteristics of the patient: the basal need and insulin sensitivity. The basal need is the amount of insulin which maintains the blood sugar level at the desired level in the course of the day, provided the subject adheres to a standard regime. The insulin sensitivity represents the sensitivity of the glucose metabolism to deviations from the basal requirement. These purely individual parameters are currently adapted by the "learning" module. The module compares the assessed and predicted blood sugar levels and corrects the parameters to achieve a minimum difference. The accuracy of approximation depends on the number of assessed blood sugar levels. The system foresees a minimum of two assessments per day. Individualized parameters are used for the prediction of the blood sugar level. The system visualizes predicted blood sugar levels for manually administered alternative insulin doses. The module of the automatic therapeutic plan is part of the module. The system recommends treatment with an "optimal" development of the predicted blood sugar level. As a criterium of the optimal profile of the blood sugar level the M-value was selected which is used for the evaluation of the daily blood sugar profile. The predictive capacity of the system was evaluated on the basis of retrospective data.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188726 TI - Emergency use of portable cardiopulmonary bypass. PMID- 2188727 TI - Use of percutaneously inserted cardiopulmonary bypass in the cardiac catheterization laboratory. AB - A cardiopulmonary bypass system that can be percutaneously inserted is available. In addition to its use in stabilization of severely hemodynamically compromised patients, it has many uses in cardiology including use as an adjunct to high-risk interventional procedures. The purpose of this report is to communicate our experience with cardiopulmonary bypass in the Catheterization Laboratory and discuss technique, indications, and potential complications. PMID- 2188728 TI - Detection and quantification of aortic regurgitation during aortic valvuloplasty. AB - The degree of aortic regurgitation, before and after balloon aortic valvuloplasty, was assessed in 32 patients, using double indicator dilution curves: a) the forward curve was obtained by dye injection into the left ventricle and sampling in the aorta; b) the regurgitant curve was obtained by dye injection in the aorta and sampling in the left ventricle. A regurgitant index (RI) was calculated by obtaining the ratio of the areas of the triangles from regurgitant and forward curves. Eight-five percent of the patients were 70 years or older. After valvuloplasty, aortic valve area increased from 0.5 +/- 0.3 cm2 to 0.7 +/- 0.3 cm2 (P = .0002) while left ventricular to aortic gradient decreased from 77 +/- 32 to 51 +/- 24 (P = .0001). RI did not significantly change in 58% of patients, increased in 25%, and decreased in 15.2%. We conclude that in most patients undergoing aortic valvuloplasty, regurgitation does not change after the procedure. In some patients it may increase significantly, and in a few it may even decrease. Indicator dilution curves technique seems to provide a sensitive, accurate, and reproducible method to detect and quantify aortic incompetence before and after valvuloplasty. PMID- 2188729 TI - Substrates for p34cdc2: in vivo veritas? PMID- 2188730 TI - Identification of cell cycle-regulated phosphorylation sites on nuclear lamin C. AB - The mechanism by which MPF induces nuclear lamin disassembly and nuclear envelope breakdown during mitosis was studied in a frog egg extract in which the transition from interphase to mitosis can be induced by the addition of MPF. Bacterially expressed human nuclear lamin C, assembled in vitro into filaments, showed increased phosphorylation on specific sites in the extract in response to MPF. Phosphorylation was accompanied by disassembly of the lamin filaments. We determined the sequences of the sites phosphorylated both in the presence and absence of MPF. The sequence data suggest that multiple protein kinases act on the lamins, and S6 kinase II was identified as one potentially important lamin kinase. PMID- 2188731 TI - In vitro disassembly of the nuclear lamina and M phase-specific phosphorylation of lamins by cdc2 kinase. AB - The nuclear lamina is an intermediate filament-type network underlying the inner nuclear membrane. Phosphorylation of lamin proteins is believed to cause lamina disassembly during meiotic and mitotic M phase, but the M phase-specific lamin kinase has not been identified. Here we show that the cdc2 kinase, a major element implicated in controlling the eukaryotic cell cycle, phosphorylates chicken B-type lamins in vitro on sites that are specifically phosphorylated during M phase in vivo. Concomitantly, cdc2 kinase is capable of inducing lamina depolymerization upon incubation with isolated nuclei. One of the target sites of cdc2 kinase is identified as a motif (SPTR) conserved in the N-terminal domain of all lamin proteins. These results lead us to propose that mitotic disassembly of the nuclear lamina results from direct phosphorylation of lamins by cdc2 kinase. PMID- 2188732 TI - Site-specific DNA repair at the nucleosome level in a yeast minichromosome. AB - The rate of excision repair of UV-induced pyrimidine dimers (PDs) was measured at specific sites in each strand of a yeast minichromosome containing an active gene (URA3), a replication origin (ARS1), and positioned nucleosomes. All six PD sites analyzed in the transcribed URA3 strand were repaired more rapidly (greater than 5-fold on average) than any of the nine PD sites analyzed in the nontranscribed strand. Efficient repair also occurred in both strands of a disrupted TRP1 gene (ten PD sites), containing four unstable nucleosomes, and in a nucleosome gap at the 5' end of URA3 (two PD sites). Conversely, slow repair occurred in both strands immediately downstream of the URA3 gene (12 of 14 PD sites). This region contains the ARS1 consensus sequence, a nucleosome gap, and two stable nucleosomes. Thus, modulation of DNA repair occurs in a simple yeast minichromosome and correlates with gene expression, nucleosome stability, and (possibly) control of replication. PMID- 2188733 TI - Distinct sets of SEC genes govern transport vesicle formation and fusion early in the secretory pathway. AB - A vesicular intermediate in protein transport from the endoplasmic reticulum is detected in a subset of temperature-sensitive mutants blocked early in the yeast secretory pathway. By electron microscopy three of the mutants, sec18, sec17, and sec22, accumulate 50 nm vesicles at the nonpermissive temperature. Vesicle accumulation is blocked by the mutations sec12, sec13, sec16, and sec23 as shown by analysis of double-mutant strains. Thus the early SEC genes can be divided into vesicle forming and vesicle fusion functions. Synthetic lethal interactions between sec mutations define two groups of SEC genes, corresponding to the groups involved in vesicle formation or fusion. Mutations in two of the genes involved in vesicle fusion, SEC17 and SEC18, are lethal in combination, and five of six possible pairwise combinations of mutations in genes required for vesicle formation, SEC12, SEC13, SEC16, and SEC23, are lethal. These interactions suggest cooperation between different SEC gene products in vesicle budding and vesicle fusion processes. PMID- 2188734 TI - Prokaryotic secretion. PMID- 2188735 TI - A genetic model for colorectal tumorigenesis. PMID- 2188736 TI - ras p21 and GAP inhibit coupling of muscarinic receptors to atrial K+ channels. AB - The signal-transducing G protein Gk couples muscarinic receptors to K+ (K+[ACh]) channels in atrial cells. Recombinant human ras p21 GAP (GTPase activating protein) at subnanomolar concentrations inhibited GTP-dependent channel opening in isolated atrial cell membranes. This inhibition depended on interaction of GAP with ras p21 in the isolated membranes. In addition, recombinant ras p21 proteins blocked the currents; this effect could be blocked by prior incubation of membranes with specific anti-GAP antibodies. We therefore propose that ras p21 GTP complexed with GAP (ras p21-GAP) blocks K+[ACh] currents. The channel block could be overcome by GTP gamma S activation of endogenous Gk; this indicates that ras p21-GAP does not interfere with interaction of Gk with the K+[ACh] channel directly, but prevents coupling of the muscarinic receptor to endogenous Gk. PMID- 2188737 TI - Interaction of adenovirus VA RNAl with the protein kinase DAI: nonequivalence of binding and function. AB - Adenovirus VA RNAL maintains protein synthesis by preventing activation of the double-stranded RNA (dsRNA)-dependent protein kinase DAI. There appears to be a single binding site for dsRNA on DAI, and this site is blocked by VA RNAl. VA RNAl binds to purified DAI and can be cross-linked to the enzyme by UV irradiation. To determine the relationship between DAI binding and VA RNAl structure and function, we examined the binding abilities of wild-type and mutant VA RNAs. In several cases, the ability to bind DAI efficiently in vitro did not correlate with function in vivo. Secondary structure analysis suggested that efficient binding requires an apical stem-loop structure, whereas inhibition of DAI activation requires the central domain of the VA RNA molecule. We propose that the duplex stem permits VA RNA to interact with the dsRNA binding site on DAI and inhibits activation by juxtaposing the central domain of the RNA with the enzyme's active site. PMID- 2188738 TI - Phenotypic analysis of the early events during repopulation of the thymus by the bone marrow prothymocyte. AB - The phenotype of the donor thymocytes present in the thymus of irradiated mice injected intravenously with CD3-depleted total bone marrow cells has been studied by three-color flow cytometry during the time period 6-16 days postinjection. Donor cells could first be reliably detected at Day 6 after reconstitution. Donor and host cells maintain their relative proportions over the first few days, after which time the proportion of donor cells derived from the bone marrow increases. At Days 6 and 7 after reconstitution, Pgp-1+, IL-2R- cells predominate, although a minority of Pgp-1+, IL-2R+ cells is also seen. Few cells are Pgp-1-, IL-2R+. Over the next 3 days, the relative proportion of Pgp-1+, IL-2R- cells declines rapidly and the relative proportion of Pgp-1+, IL-2R+ cells and then of Pgp-1-, IL-2R+ cells peaks and declines. The absolute number of all three populations, however, increases exponentially until Day 14. Most donor cells present at Days 6 7 after reconstitution are L3T4-, Lyt-2-. Over the next 2 days, the majority of donor-derived cells express low, but significant, levels of both L3T4 and Lyt-2. L3T4+, Lyt-2+ cells expressing levels of cell surface antigen characteristic of the cognate population found in the adult first appear at Day 10 after reconstitution. These L3T4+, Lyt-2+ donor cells increase in proportion to reach 70-80% of donor-derived cells after Day 14 of reconstitution. The host thymocyte population, on the other hand, contains few Pgp-1+ or IL-2R+ cells even at 7 days after irradiation and is predominantly L3T4+, Lyt-2+ by Day 8. This observation suggests that the host cells are derived from a more mature precursor than the bone marrow prothymocyte or the earliest intrathymic progenitors. PMID- 2188739 TI - Growth inhibition of Candida albicans by interleukin-2-induced lymph node cells. AB - Previous reports have demonstrated natural killer cells (NK) to exert growth inhibitory effects against certain fungi, but not against Candida albicans. In this investigation, interleukin-2 (IL-2)-induced lymph node cells with phenotypic and functional characteristics of NK were shown to inhibit the growth of C. albicans. Growth inhibition was evaluated by both the release of 51Cr by the fungus and the inhibition of microcolony growth of the fungus on Sabouraud's dextrose agar. Lymphoid cells derived from C57Bl/6 mice and immediately assessed for hyphal growth inhibition showed little or no activity. However, significant hyphal growth inhibition was produced by lymph node cells cultured with recombinant IL-2. Growth inhibitory activity was dependent upon the concentration of IL-2 and was mediated by nonadherent lymphocytes which lysed an NK-susceptible and to a lesser extent an NK-resistant cell line. Treatment of the IL-2-induced cells with anti-asialo GM1 but not anti-Thy-1 and complement abrogated growth inhibition of C. albicans. These results suggest that IL-2-induced lymph node cells with functional and phenotypic characteristics similar to those of activated NK, mediate in vitro growth inhibition of the hyphal form of C. albicans. PMID- 2188740 TI - Vimentin in human erythroleukemia (HEL) cells is modulated with differentiation inducers. AB - The expression of vimentin intermediate filaments (IFs) was studied in a human erythroleukemia cell line (HEL), exposed to a variety of differentiation-inducing agents. These cells grow normally in suspension and show a heterogenous expression of vimentin immunoreactivity. In the presence of retinoic acid the fibrillar vimentin immunoreactivity diminished rapidly, while it was increased when the cells were exposed to hemin or butyric acid. In the presence of a tumor promoter (TPA), the HEL cells maintained their heterogenous vimentin immunoreactivity, but some cells showed large bundles of cytoplasmic vimentin fibrils. Upon exposure to TPA the cells spread on a growth substratum covered with human plasma fibronectin (Fn). Many of the spread cells totally lacked vimentin IFs. The present results show that vimentin expression in HEL cells is rapidly and differentially modulated upon exposure to the different inducing agents. PMID- 2188742 TI - Immunocytochemical demonstration of skeletal muscle type peptidylarginine deiminase in various rat tissues. AB - We have performed an immunocytochemical study of peptidylarginine deiminase (EC 3.5.3.15) in various rat tissues using an antiserum to the enzyme purified from rat skeletal muscle. Staining was observed in skeletal muscle fibers, glia cells of the central nervous system, serous cells of submandibular gland, demilunar cells (serous cells) of sublingual gland, uterine endometrium and myometrium, and certain cells in the lamina propria of intestinal villi. Possible involvement of the enzyme in multiple cellular processes were discussed. PMID- 2188741 TI - Insulin and step-up conditions cause a redistribution of polysomes among free, cytoskeletal-bound and membrane-bound fractions in Krebs II ascites cells. AB - From 30 min to 1h of step-up conditions there was a redistribution of polysomes between free, cytoskeletal-bound and membrane-bound fractions such that more polysomes were recovered bound to the cytoskeleton and less in the free fraction. After 1h incubation with insulin there was a higher proportion of polysomes in the cytoskeletal fraction with a decrease occurring in the membrane-bound fraction. At 2h little change was observed in the presence of insulin while a large increase occurred in the cytoskeletal-bound fraction and a decrease in membrane-bound polysomes was seen in cells incubated in the absence of insulin. The results indicate that the proportions of polysomes in the three different fractions can be modulated by physiological stimuli, such as media replenishment and insulin. PMID- 2188743 TI - [Prenatal ultrasonic diagnosis of congenital developmental defects. I. Introduction, pathology of the head, spine and thorax]. PMID- 2188744 TI - [Kuster or Kustner?]. PMID- 2188745 TI - [The beginnings of Czechoslovak neurology from the aspect of personal memories]. PMID- 2188746 TI - [The role of the whole-body stereotaxic apparatus in directed interventions in humans]. AB - All-body aiming apparatuses in conjunction with computed tomography are a new promise in the diagnostic and therapeutic complex. They make it possible to reach any point inside the body from any point on its surface. The space where the target is found is operated by the arms of the apparatus in three planes normal to each other and by rotating two angles round the longitudinal and transverse axis. Guiding of the apparatus on the target is controlled by the computer programme. Immobilization of the patient is achieved by a vacuum cushion. The apparatus was tested under model conditions and is ready for clinical use. PMID- 2188747 TI - [The ultrasonographic picture of the normal wall of the gastrointestinal tract and changes due to tumors or inflammatory conditions]. PMID- 2188748 TI - Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability. AB - Resistance to endotoxin in essential fatty acid-deficient (EFAD) rats is associated with reduced synthesis of certain arachidonic acid metabolites. It was hypothesized that EFAD rats would manifest decreased vascular permeability changes during endotoxemia as a consequence of reduced arachidonic acid metabolism. To test this hypothesis, changes in hematocrit (HCT) and mesenteric localization rate of technetium-labeled human serum albumin (99mTc-HSA) and red blood cells (99mTc-RBC) were assessed in EFAD and normal rats using gamma-camera imaging. Thirty minutes after Salmonella enteritidis endotoxin, EFAD rats exhibited less hemoconcentration as determined by % HCT than normal rats (47 +/- 2% vs. 54 +/- 1% respectively, P less than 0.01). Endotoxin caused a less severe change in permeability index in the splanchnic region in EFAD rats than in normal rats (1.2 +/- 0.6 x 10(-3)min-1 vs. 4.9 +/- 1.7 x 10(-3)min-1 respectively, P less than 0.05). In contrast to 99mTc-HSA, mesenteric localization of 99mTc-RBC was not changed by endotoxin in control or EFAD rats. Supplementation with ethyl arachidonic acid did not enhance susceptibility of EFAD rats to endotoxin-induced splanchnic permeability to 99mTc-HSA. Leukotrienes have been implicated as mediators of increased vascular permeability in endotoxin shock. Since LTC3 formation has been reported to be increased in EFA deficiency, we hypothesized that LTC3 may be less potent than LTC4. Thus the effect of LTC3 on mean arterial pressure and permeability was compared to LTC4 in normal rats. LTC3-induced increases in peak mean arterial pressure were less than LTC4 at 10 micrograms/kg (39 +/- 5 mm Hg vs. 58 +/- 4 mm Hg respectively, P less than 0.05) and at 20 micrograms/kg (56 +/- 4 mm Hg vs. 75 +/- 2 mm Hg respectively, P less than 0.05). LY171883 (30 mg/kg), an LTD4/E4 receptor antagonist, attenuated the pressor effect of LTC4, LTD4, and LTC3. Infusion of LTC4 (4 micrograms/kg/min) in normal rats induced a rise in HCT from 44 +/- 1% to 51 +/- 1% (P less than 0.01), which was greater (P less than 0.05) than the rise induced by LTC3 (47 +/- 1% to 49 +/- 1%). The results showing that EFAD rats are resistant to endotoxin-induced increases in HCT and vascular permeability raise the possibility that this may, in part, be a result of preferential LTC3 production that is less potent than LTC4. PMID- 2188749 TI - Baroreceptor-heart rate reflex function before and after surgical reversal of two kidney, one-clip hypertension in the rat. AB - Baroreflex function was studied in conscious early phase (less than 6 weeks) two kidney, one-clip hypertensive rats before and 24 hours after surgical reversal of hypertension by removal of the constricting renal artery clip or after pharmacological reduction of blood pressure by an infusion of hydralazine or captopril. A normotensive sham-clipped group was included. Another group of two kidney, one-clip rats was studied 3 weeks after unclipping. Baroreflex sensitivity, as assessed by the steady-state method using a graded phenylephrine infusion, mean arterial pressure, and heart rate were measured preoperatively and at 24 hours postoperatively. Two-kidney, one-clip rats were significantly hypertensive preoperatively compared with control (mean arterial pressure, 183 +/ 4 vs. 106 +/- 2 mm Hg, p less than 0.001), heart rate was similar (420 +/- 9 vs. 401 +/- 9 beats/min, p greater than 0.05), and baroreflex sensitivity was significantly reduced (0.76 +/- 0.07 vs. 1.50 +/- 0.20 msec/mm Hg; p less than 0.001). There was a minimal change in heart rate despite the fall in mean arterial pressure in all hypertensive groups, indicating resetting of the baroreflexes. At 24 hours after the operation, baroreflex sensitivity was unchanged in all groups compared with the preoperative value. By 3 weeks, baroreflex sensitivity was significantly greater than in the hypertensive two kidney, one-clip rats before the operation and 24 hours after they were unclipped, but not compared with normotensive sham-clipped rats. Thus, although resetting occurs within 24 hours, whatever the method of blood pressure reduction, baroreflex sensitivity remains impaired at this time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188750 TI - Induction of insulin-like growth factor I messenger RNA in rat aorta after balloon denudation. AB - Insulin-like growth factor I (IGF-I) is a widely distributed mitogen that mediates the growth-promoting effects of platelet-derived growth factor in mesenchymal cells. We show that rat aortic IGF-I messenger RNA (mRNA) is induced 24 hours after deendothelialization, at a time when smooth muscle cell proliferation within the intima is still not apparent. After 7 days, IGF-I mRNA induction peaks at about ninefold control levels and then falls to about threefold 14 days after denudation when smooth muscle cell proliferation is at its peak. We also show that, of the 5' untranslated IGF-I mRNA transcripts, only the class C transcript is expressed and regulated in aortic tissue. In contrast, treatment of rats with supraphysiological doses of growth hormone, the major endocrine regulator of IGF-I gene expression, elicited only twofold induction of aortic IGF-I mRNA. Our findings suggest that IGF-I may be an important autocrine or paracrine regulator of smooth muscle cell proliferation and that it may be significant in determining the cellular response to arterial wall injury. PMID- 2188751 TI - Chronic major-vessel thromboembolic pulmonary hypertension. PMID- 2188752 TI - Treatment of 150 cases of life-threatening digitalis intoxication with digoxin specific Fab antibody fragments. Final report of a multicenter study. AB - One hundred fifty patients with potentially life-threatening digitalis toxicity were treated with digoxin-specific antibody fragments (Fab) purified from immunoglobulin G produced in sheep. The dose of Fab fragments was equal to the amount of digoxin or digitoxin in the patient's body as estimated from medical histories or determinations of serum digoxin or digitoxin concentrations. The youngest patient received Fab fragments within several hours of birth, and the oldest patient was 94 years old. Seventy-five patients (50%) were receiving long term digitalis therapy, 15 (10%) had taken a large overdose of digitalis accidentally, and 59 (39%) had ingested an overdose of digitalis with suicidal intent. The clinical response to Fab was unspecified in two cases, leaving 148 patients who could be evaluated. One hundred nineteen patients (80%) had resolution of all signs and symptoms of digitalis toxicity, 14 (10%) improved, and 15 (10%) showed no response. After termination of the Fab infusion, the median time to initial response was 19 minutes, and 75% of the patients had some evidence of a response by 60 minutes. There were only 14 patients with adverse events considered to possibly or probably have been caused by Fab; the most common events were rapid development of hypokalemia and exacerbation of congestive heart failure. No allergic reactions were identified in response to Fab treatment. Of patients who experienced cardiac arrest as a manifestation of digitalis toxicity, 54% survived hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188753 TI - A controlled trial of corticosteroids to prevent restenosis after coronary angioplasty. M-HEART Group. AB - A multicenter, double-blind, placebo-controlled trial was conducted to determine if corticosteroids influence the development of restenosis after successful percutaneous transluminal coronary angioplasty (PTCA). Either placebo or 1.0 g methylprednisolone (steroid) was infused intravenously 2-24 hours before planned PTCA in 915 patients. The PTCA patient success rate was 87% (mean) in the eight centers. There were no differences in clinical or angiographic baseline variables between the two groups. End-point analysis (angiographic restenosis, death, recurrent ischemia necessitating early restudy, and coronary artery bypass graft surgery) showed that there was no significant difference comparing placebo- with steroid-treated patients. Angiographic restudy showed the lesion restenosis rate to be 39% (120 of 307 lesions) after placebo and 40% (117 of 291) after steroid treatment (p = NS). We conclude that pulse steroid pretreatment does not influence the overall restenosis rate after successful PTCA. PMID- 2188754 TI - Assessment of renin dependency of hypertension with a dipeptide renin inhibitor. AB - To evaluate the participation of the renin-angiotensin system in sustaining hypertension, we administered the specific dipeptide renin inhibitor enalkiren (A 64662) to 18 patients with essential hypertension. Ascending intravenous bolus doses (0.03, 0.1, 0.3, and 1.0 mg/kg) of the inhibitor were each given at 45 minute intervals to patients maintained on an ad libitum sodium diet who were studied while in bed in the semirecumbent posture. Enalkiren produced marked decreases in plasma renin activity (PRA) that were still evident 8 hours after completion of dosing. Systolic and diastolic blood pressures were decreased in a dose-dependent fashion without an effect on heart rate. Repetition of this procedure after patients were subjected to sodium depletion by 1 week of thiazide treatment produced amplified decreases in blood pressure. Despite the short plasma half-life of the inhibitor, these blood pressure-lowering effects were sustained for 4-8 hours when compared with parallel placebo administration in the same patients. Both the baseline PRA and the inhibitor-induced changes in PRA correlated significantly with blood pressure changes during the unstimulated and the sodium-depleted studies. However, effects of the inhibitor on diastolic blood pressure in the latter study correlated most closely with actual increases in renin produced by diuretic pretreatment. Thus, this specific renin inhibitor has demonstrated the dependency of blood pressure on the renin-angiotensin system even during basal conditions in hypertensive patients. Moreover, renin response to sodium depletion appears to be an attribute that additionally characterizes individual hypertensive patients. PMID- 2188755 TI - Involvement of endothelin in the regulation of human vascular tonus. Potent vasoconstrictor effect and existence in endothelial cells. AB - Endothelin, a recently discovered endothelium-derived peptide, has been reported to produce potent vasoconstriction in various vessels of experimental animals. To study the involvement of endothelin in the regulation of vascular tonus in humans, isolated human mesenteric arteries were investigated by both pharmacological and immunohistochemical methods. The vasoconstrictor action of endothelin-1 was examined on ring segments of human mesenteric arteries. Endothelin-1 induced a slowly developing and sustained contraction, with an EC50 value (half-maximal effective concentration) of 2.9 x 10(-9) M, two orders of magnitude smaller than that of norepinephrine (EC50 of 3.9 x 10(-7) M), indicating that the vasoconstrictor action of endothelin-1 is about 100 times more potent than that of norepinephrine. The contractile effect of endothelin-1 was affected neither by adrenergic, cholinergic, histaminergic, nor serotonergic antagonists, nor by inhibitors of arachidonic acid metabolism. The vasoconstrictor response to endothelin-1 was effectively antagonized by nicardipine, a dihydropyridine Ca2+ channel blocker. Endothelin-1 profoundly augmented contractile response to Ca2+ in partially depolarized tissues. Immunohistochemical studies revealed for the first time that endothelin-like immunoreactivity was localized in endothelial cells of human mesenteric artery. The results of the present study indicate that endothelin-1 is one of the most potent vasoconstrictors in the human mesenteric artery and that it induces vasoconstriction via an ultimately accelerating Ca2+ influx through voltage dependent Ca2+ channels. Since endothelin-1 can be located in human endothelial cells, it may play an important physiological or pathophysiological role. PMID- 2188756 TI - Physiological and immunopathological consequences of active immunization of spontaneously hypertensive and normotensive rats against murine renin. AB - Spontaneously hypertensive Okamoto-strain rats (SHR) and normotensive Wistar Kyoto (WKY) rats were actively immunized with mouse renin to investigate the effect on blood pressure of blocking the renin-angiotensinogen reaction. Ten male SHR and 10 male WKY rats were immunized with purified mouse submandibular gland renin. Control rats were immunized with bovine serum albumin. Antirenin antibodies were produced by both SHR and WKY rats, but renin-immunized SHR had higher titers of circulating renin antibodies after three injections. The increase in renin antibody in renin-immunized SHR was associated with a significant drop in blood pressure (tail-cuff method) that became similar to that of the WKY control rats after four injections. The blockade by antirenin immunoglobulins of the renin-angiotensinogen reaction also decreased the blood pressure of normotensive rats. Perfusion of renin-immunized rats with mouse submandibular renin (10 micrograms) in vivo caused no increase in blood pressure. Perfusion of renin-immunized, salt-depleted SHR with converting enzyme inhibitor caused no further decrease in blood pressure but significantly decreased blood pressure in salt-depleted control rats. The presence of circulating renin antibodies was associated with low plasma renin activity (0.31 +/- 0.23 ng angiotensin I [Ang I]/ml/hr). Plasma renin activity was unchanged in control animals (13.1 +/- 3.9 ng Ang I/ml/hr in control SHR, 13.9 +/- 3.2 ng Ang I/ml/hr in control WKY rats). Renin antibody-rich serum produced a dose-dependent inhibition of rat renin enzymatic activity in vitro. The chronic blockade of the renin-angiotensinogen reaction in renin-immunized SHR produced an almost-complete disappearance of Ang II (0.8 %/- 7 fmol/ml; control SHR, 30.6 +/- 15.7 fmol/ml) and a 50% reduction in urinary aldosterone. Renin immunization was never associated with a detectable loss of sodium after either 10 or 24 weeks. The glomerular filtration rate was not decreased 10 weeks after renin immunization, whereas blood pressure was significantly decreased, plasma renin activity was blocked, and renal plasma flow was increased. The ratio of left ventricular weight to body weight after 24 weeks was significantly below control levels in renin-immunized WKY rats and SHR. Histological examination of the kidney of renin immunized SHR showed a chronic autoimmune interstitial nephritis characterized by the presence of immunoglobulins, mononuclear cell infiltration, and fibrosis around the juxtaglomerular apparatus. These experiments demonstrate that chronic specific blockade of renin decreases blood pressure in a genetic model of hypertension in which the renin-angiotensin system is not directly involved.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2188757 TI - Coronary artery spasm and vasoconstriction. The case for a distinction. PMID- 2188758 TI - Computerized tabulation of cine coronary angiograms. Its implication for results of randomized trials. AB - The quality of cine angiography is excellent in our days, and as a consequence some of the pitfalls encountered in previous randomized trials are not currently present. An example can be found in the CASS analysis of the reproducibility of coronary arteriographic reading by the Quality Control Committee Sessions: "There is an indication that different clinics" involved in the CASS trial "can reduce the variability between their readings by concerted effort to improve both the quality and the completeness of the angiographic examination." The introduction of electronic calipers to judge the severity of the obstruction can eliminate human errors. The computerized protocol has the disadvantage that it takes longer to tabulate cine coronary angiography and it will depend on its pattern, but it certainly will not be as long as filling in the CASS protocol. However, this effort is justified because it will enrich our knowledge of coronary arteriosclerosis. As a result, patients will be divided into proximal (1, 2, 12, 13, and 19), middle (mainly, 3, 14, and 20), and distal (remainder) segments. Sometimes midsegments can be important. For example, in the report from CASS related to the left main equivalent lesions, the 5-year survival rate was 48% if the obstruction on the left anterior descending was proximal and increased to 71% if it was more distal. Several randomized studies to compare PTCA with CABG as suggested by Gruentzig et al in 1979 are underway, and it is hoped that the data will be properly analyzed. However, if cine coronary angiography and the status of the left ventricle are not carefully tabulated (classification of patients into left main trunk or one-, two-, or three-vessel disease is not sufficient), the results of the randomized trials comparing PTCA with CABG will add more confusion instead of clarifying proper therapeutic implications. PMID- 2188759 TI - Hyperhomocyst(e)inemia. A common and easily reversible risk factor for occlusive atherosclerosis. PMID- 2188760 TI - Intracardiac, intravascular, two-dimensional, high-frequency ultrasound imaging of pulmonary artery and its branches in humans and animals. AB - Intravascular ultrasound imaging is a promising new method for assessing vascular morphology. We evaluated the capability of intravascular ultrasound to quantify pulmonary artery (PA) morphology in vitro and explored the feasibility of in vivo PA imaging in animals and humans. In the in vitro study of 15 PA segments, we used a 20-MHz prototype ultrasound catheter. Intravascular ultrasound (y) provided crisp images of PA segments and demonstrated excellent correlations with anatomic measurements (x) in the estimation of luminal area (y = 0.89x + 2.95, r = 0.99, p less than 0.001), luminal diameter (n = 30, y = 0.79x + 0.96, r = 0.92, p less than 0.001), and vessel wall thickness (n = 60, y = 0.65x + 0.33, r = 0.85, p less than 0.001). We subsequently introduced the probe into the PA of 10 dogs and were able to obtain real-time, two-dimensional images of the main PA, its major branches, and farther smaller branches as far as the wedge level. To evaluate the in vivo feasibility of PA imaging in conscious humans, we used a commercially available, 20-MHz intravascular ultrasound (IVUS) catheter in 22 subjects through a femoral or jugular venous sheath at the end of standard diagnostic cardiac catheterization. In 20 subjects, we acquired dynamic, high resolution, cross-sectional images of the proximal and distal PA. Changes in shape and decreasing luminal area could be clearly recognized as the IVUS catheter reached branching points and as it passed more distally. There were no complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188761 TI - Excimer laser atherectomy. The greening of Sisyphus. PMID- 2188762 TI - The endothelin explosion. A pathophysiological reality or a biological curiosity? PMID- 2188763 TI - Aminopropylidine diphosphonate (APD) in mild primary hyperparathyroidism: effect on clinical status. AB - Mild hypercalcaemia associated with primary hyperparathyroidism has been increasingly recognized with the use of automated biochemical screening. Management is often difficult as symptoms are often absent or non-specific. Accordingly, we employed the hypocalcaemic effect of the diphosphonate APD to assess the effect of an acute fall in plasma calcium on indices of general well being, blood pressure, and vasoactive hormones in patients with mild primary hyperparathyroidism. Ten patients were studied in a randomized single blind, placebo-controlled cross-over study, using 30 mg APD intravenously or control saline infusion, over 2 h. Metabolic measurements, formal tests of muscle strength and cognitive function, and a standardized questionnaire were assessed 7 days after infusions. Albumin corrected plasma calcium was significantly lower (mean 2.49 +/- 0.04 SEM mmol/l) after APD when compared to control values (2.70 +/- 0.06 mmol/l, P less than 0.001). Twenty-four-hour urinary calcium, plasma magnesium and absolute monocyte count decreased significantly, whereas plasma parathyroid hormone increased after APD (P less than 0.05). There was no significant change in hypercalcaemic symptoms, muscle strength or cognitive function, and blood pressure, renin, aldosterone and atrial natriuretic peptide did not change. Side-effects, when they occurred, were mild. It is concluded that APD is a safe and effective means of lowering plasma calcium in mild primary hyperparathyroidism, but these acute reductions are associated with little or no improvement in clinical status in these patients. PMID- 2188764 TI - Future directions in plasminogen activator therapy. AB - Thrombotic disorders such as myocardial infarction and stroke are the leading causes of death and disability in industrialized nations. Timely institution of thrombolytic therapy can achieve a reduction of infarct size, a preservation of left ventricular function, and a reduction in mortality. The administration of streptokinase, urokinase, and acylated plasminogen-streptokinase activator complex (APSAC) can be associated with a complete breakdown of the hemostatic system. Tissue-type plasminogen activator (t-PA) and single-chain urokinase-type plasminogen activator (scu-PA, prourokinase) are more fibrin specific; however, at the large dosages of activator needed for therapeutic efficacy, bleeding complications are still a problem. New approaches to optimizing the risk/benefit ratio for the patient by improving efficacy without sacrificing specificity include the use of synergistic combinations of plasminogen activators, mutants of t-PA and scu-PA, chimeric molecules, and antibody-targeted thrombolytic agents. The last approach opens the possibility of targeting several different components of the clot with either fibrinolytic or antiplatelet effector functions in one optimized molecule. PMID- 2188765 TI - Primary pulmonary hypertension in adults. AB - Primary pulmonary hypertension is an enigmatic disease found predominantly in young women, but it also affects a significant number of middle-aged and elderly males and females. Its onset, characterized by progressively worsening dyspnea, fatigue, and chest pain, is insidious. Three distinct histopathologic subtypes have been identified, and the natural history of the disease process has been well-defined. Pharmacologic treatment options have, in general, been disappointing, and it appears that heart-lung transplantation will be applied only to a small minority of young patients with primary pulmonary hypertension in the near future. We review the histopathology, evaluation, treatment, and prognosis of primary pulmonary hypertension. PMID- 2188766 TI - Chronic vasodilator therapy with flosequinan in congestive heart failure. AB - This study was conducted to determine the long-term effect of flosequinan, a new orally administered arterial and venous dilator, on the clinical course of patients with moderate to severe congestive heart failure. Seventeen patients on chronic digitalis and diuretic therapy were randomized to receive either flosequinan (n = 9) or placebo (n = 8) in a double-blind fashion. Changes in symptomatology, exercise performance, and left ventricular function were assessed serially during the two-month treatment period. During the course of therapy, a modest improvement in the symptom scores and functional classification of the flosequinan-treated patients was observed. Flosequinan evoked a significant increase in maximal exercise capacity. While long-term flosequinan administration also effected a progressive increase in resting heart rate, it did not consistently improve indices of left ventricular systolic function. The addition of chronic vasodilator therapy with flosequinan to standard digitalis-diuretic regimens is capable of inducing clinical improvement in patients with moderate to severe chronic heart failure. Trials involving larger patient populations will be necessary to confirm the results of this preliminary study and to determine the extent of clinical improvement, subpopulations benefited, role in heart failure therapeutics, and so forth. PMID- 2188767 TI - Biophysical and anatomical considerations for safe and efficacious catheter ablation of arrhythmias. AB - The development of catheter ablation techniques for therapy of cardiac arrhythmias continues to evolve. Although many patients have benefited from catheter ablation procedures, failure to ablate the arrhythmogenic substrate and complications from the pulse used in these procedures remain too frequent occurrences. The purpose of this review is to focus on these problems of inefficacy and safety with attention directed to the role various direct current and radiofrequency pulses have had in the genesis of these difficulties. PMID- 2188768 TI - Topography of atherosclerotic coronary artery disease. AB - This article reviews several issues relevant to current interest in coronary angioplasty, acute reperfusion, and the use of new interventional devices (stents, probes, atherectomy devices, etc.): diffuse versus focal nature of plaque, the number of vessels severely diseased, quantitation of luminal stenosis and length of stenosis, and the distribution of plaque in the four major coronary arteries in various clinical ischemic subsets. PMID- 2188769 TI - Thomas Bevill Peacock. PMID- 2188770 TI - Pharmacokinetics and erythropoietic response to human recombinant erythropoietin in healthy men. AB - To assess the safety, pharmacokinetics, and erythropoietic responses to human recombinant erythropoietin (epoetin beta), single intravenous doses (10, 50, 150, and 500 IU/kg) were administered at monthly intervals to 16 healthy subjects in a two-panel, placebo-controlled, double-blind ascending-dose trial. A 1000 IU/kg dose was subsequently administered in an open manner. Epoetin concentrations were determined in serum and urine by radioimmunoassay. Reticulocyte, hemoglobin, and hematocrit values were serially measured after each dose. Mean epoetin apparent half-lives ranged from 4.42 to 11.02 hours. The apparent volume of distribution was between 40 and 90 ml/kg, consistent with plasma water, and the apparent clearance values ranged from 4 to 15 ml/kg/hr, with both parameters having the highest values at the 10 IU/kg dose level. Clearance tended to decrease as a function of dose. Maximum reticulocyte counts were dose-dependent and occurred 3 to 4 days after the epoetin dose. Epoetin was well tolerated, and no antibodies were detected. PMID- 2188771 TI - Pharmacokinetic-pharmacodynamic relationships of methadone infusions in patients with cancer pain. AB - To determine the relationship between changes in plasma methadone concentration and pharmacodynamic effects, plasma methadone profiles and pharmacodynamics (analgesia and sedation) were measured during and after the continuous infusion of methadone for 180 to 270 minutes in 15 patients with pain caused by cancer. An increase in plasma methadone concentration resulted in a rapid increase in pain relief or sedation. The estimates of values of 50% of maximum effect (Css50) for pain relief and sedation obtained with a pharmacokinetic-pharmacodynamic model varied tenfold to twentyfold among patients; the mean Css50 value for pain relief (0.359 +/- 0.158 [SD] micrograms/ml) was virtually the same as the mean Css50 value for sedation (0.336 +/- 0.205 [SD] micrograms/ml). Similarly, the mean gamma (slope function) for pain relief (4.4 +/- 3.8 [SD]) and sedation (5.8 +/- 5.4 [SD]) did not differ. Examination of hysteresis plots of data obtained during the infusion and for 4 to 5 hours after cessation of the infusion revealed a very rapid equilibration between plasma methadone values and the sites mediating pain relief. There was no indication of the development of tolerance to the pharmacodynamic effects of methadone during the study. This report describes a method for quantitating the pharmacokinetic-pharmacodynamic relationships of the desirable and undesirable effects of opioid analgesics. PMID- 2188772 TI - Diurnal blood pressure in patients with mild-to-moderate hypertension treated with once-daily benazepril hydrochloride. AB - This study evaluated the blood pressure effects of administration of once daily oral benazepril hydrochloride, a new angiotensin-converting enzyme (ACE) inhibitor, for mild-to-moderate hypertension. After a 2 to 4 week placebo baseline period, patients with diastolic blood pressure between 95 and 114 mm Hg, were randomized to receive either placebo or benazepril hydrochloride, 5, 10, 20, or 40 mg, once daily in double-blind fashion for 28 days. Blood pressure was measured predose and at 1, 2, 3, 4, 6, 8, 12, 16, 20, and 24 hours after the dose during inpatient observation days at the end of the placebo baseline period, and on the first and last day of the double-blind treatment period; and 24 hours after the dose at weekly outpatient visits. All doses of benazepril hydrochloride resulted in clinically important reductions in diastolic and systolic blood pressures that lasted between 12 and 24 hours after both the first dose, and following the last dose after 4 weeks of treatment. The findings indicate that benazepril hydrochloride may be clinically useful as once-daily monotherapy in many patients with hypertension. PMID- 2188773 TI - Novel multivalent effects of pyrazinoylguanidine in patients with azotemia. AB - In patients with azotemia, urea excretion, urea clearance, and urea/creatinine clearance ratio were increased by pyrazinoylguanidine in a dose-related manner. Urine volume and excretion of sodium greater than chloride greater than potassium tended to increase during administration of pyrazinoylguanidine. Systemic arterial pressure declined while pyrazinoylguanidine was given at 300 or 600 mg b.i.d. for 3 days. At both doses pyrazinoylguanidine reduced plasma renin activity during the first 2 hours. Between days 1 and 3 only the high dose of pyrazinoylguanidine decreased plasma renin activity and plasma aldosterone levels. These findings with pyrazinoylguanidine are consistent with those of secretion of urea in human subjects across the renal tubules and indicate that this process is susceptible to pharmacologic alteration, even in the presence of severe renal insufficiency. PMID- 2188774 TI - Morphine and oxycodone hydrochloride in the management of cancer pain. AB - In a double-blind crossover study, morphine and oxycodone hydrochloride were administered to 20 patients who were experiencing severe cancer pain. The peroral doses were determined on the basis of patient-controlled intravenous titration. The assumed oral bioavailability ratios were 44% (group 1, first 10 patients) and 33% (group 2, last 10 patients) for morphine and 66% (group 1) and 50% (group 2) for oxycodone hydrochloride, respectively. However, the patients were able to readjust their oral dosings. Equal analgesia was achieved with both drugs, but the intravenous dose of oxycodone hydrochloride needed was 30% higher than that of morphine. The median calculated oral/intravenous ratios giving comparable analgesia were 0.31 for morphine and 0.70 for oxycodone hydrochloride. Morphine caused more nausea than oxycodone hydrochloride and hallucinations occurred only during morphine treatment. Otherwise, there were no major differences in the side effects between these two opioids. PMID- 2188775 TI - The use of D-Dimer assay by enzyme immunoassay and latex agglutination techniques in the diagnosis of deep vein thrombosis. AB - The blood of 107 patients undergoing venography for suspected deep vein thrombosis (DVT) was tested for D-Dimers using enzyme immunoassay (EIA) and two latex agglutination techniques. D-Dimer levels by EIA were raised in 88% of patients with proven DVT. However, levels detected with the two agglutination tests were much less sensitive, being raised in only 43% patients with DVT. A more sensitive rapid screening test is needed to provide a useful non-invasive test for the exclusion of DVT. PMID- 2188776 TI - Community care of the seriously mentally ill: continuing problems and current issues. AB - The crisis in community care for the seriously mentally ill (SMI) stems from organizational and financial difficulties as well as from deeply embedded structural factors. The analysis shows a preference for medicalizing and individualizing the problems of SMI rather than viewing them as structural social welfare issues. The author discusses problems of deinstitutionalization, homelessness, service provisions, financing, accounting and reporting, employment, bureaucratic skimming and burden to families and points out the ambivalent ideology and the inherent contradictions within the mental health service system. Finally, the centrality of social control and the maintenance of orderly social life in public policy and program development is illuminated. PMID- 2188777 TI - Reflections prompted by the Community Mental Health Journal. AB - Recalled are some of the earlier history of the Community Mental Health Journal and the context of ideas in which it was nourished. What was accomplished and what is now needed is also addressed. PMID- 2188778 TI - Trypanosoma (Schizotrypanum) cruzi: repetitive DNA sequence evolution in three geographically distinct isolates. AB - 1. Middle-repetitive DNA sequences were analyzed by molecular hybridization to determine both the extent of complementarity and time of evolutionary divergence between isolates of Trypanosoma cruzi from Argentina, Mexico, or Venezuela. 2. Although molecular hybridizations showed no significant difference between the middle-repetitive DNAs of the Mexican and Venezuelan isolates, there was a 2.7% base pair mismatch in hybrid molecules formed by association of strands from both the Mexican and Argentine isolates. 3. Using the rates for divergence of middle repetitive DNA in sea urchins, the Mexican and Argentine isolates were estimated to have diverged approximately 20-25 million years ago. 4. Analysis of the kinetics for the DNA hybridizations indicates that only minor amplifications of specific gene sequences or changes in the complexity of the genomes could have occurred during the divergence of the three isolates studied. PMID- 2188779 TI - The pancornulins: a group of basic low molecular weight proteins in mammalian epidermis and epithelium that may function as cornified envelope precursors. AB - 1. A monoclonal antibody (HCE-2) to human epidermal and epithelial cornified envelopes identified a group of soluble basic protein precursors. 2. Using HCE-2, envelope-like staining was observed in the epidermis and stratified squamous epithelium of a number of mammalian species. 3. Basic polypeptides reactive to HCE-2 varied in size and number among the different animals. 4. In those species studied, HCE-2-reactive peptides were substrates for transglutaminase and protease treatment of cornified envelopes released HCE-2-reactive degradation products. 5. These results suggest a new family of proteins in mammalian epidermis that may function as cornified envelope precursors. PMID- 2188780 TI - Sexual dysfunction in uremia. Endocrine and neurological alterations. PMID- 2188783 TI - Renal damage in drug abusers. PMID- 2188781 TI - Cellular calcium in the pathogenesis of ischemic acute renal failure. PMID- 2188782 TI - Oxygen free radicals in mediating tissue damage: role in nephrological settings. PMID- 2188784 TI - Bone and joints alterations in uremic patients. Role of parathyroid hormone. PMID- 2188785 TI - Role of aluminum in uremic osteodystrophy. PMID- 2188786 TI - Beta-2-microglobulin amyloidosis and osteo-articular pathology of the uremic patient on regular dialysis. PMID- 2188787 TI - Histological types of renal osteodystrophy and their meaning. PMID- 2188788 TI - Potential factors responsible for the progression of renal failure. An overview. PMID- 2188789 TI - Protein catabolic factors in patients on renal replacement therapy. PMID- 2188790 TI - Efficacy of flow-by during continuous positive airway pressure ventilation. AB - We investigated clinically the differences in respiratory work of patients imposed by three modes of one ventilator: the flow-by system, the demand valve system, and the pressure support system. Inspiratory work using flow-by and pressure support systems was reduced sufficiently when compared to the demand valve system. Moreover, fluctuation of the airway pressure was minimal with the flow-by mode. These results suggest that the flow-by mode is beneficial to patients breathing spontaneously with continuous positive airway pressure. PMID- 2188791 TI - Pathophysiology of severe forms of falciparum malaria. AB - We studied 26 patients with severe falciparum malaria who were admitted to an ICU in Namibia. The pathophysiologic effects on various organ systems are documented and the mortality associated with organ failure is reported. Patients with three or more organ failures showed a high mortality, especially when pulmonary or renal failure occurred. Predicted mortality based on the Acute Physiology and Chronic Health Evaluation II scoring system was 34% compared to an actual mortality of 38%. PMID- 2188792 TI - When is an increase in the work of breathing clinically significant? PMID- 2188793 TI - Cost and survival results of critical care regionalization for Medicare patients. PMID- 2188794 TI - A placebo-controlled, double-blind study of eicosapentaenoic acid-rich fish oil in patients with stable angina pectoris. AB - A study was carried out to evaluate the clinical and haematological effects of dietary supplementation with eicosapentaenoic acid (EPA)-rich fish oil (MaxEPA', 2.8 g EPA daily) compared to placebo (olive oil) in 10 patients with stable angina pectoris. After 3 months, there was a significant increase in red cell deformability (p less than 0.001), reduced whole blood viscosity (p less than 0.02), and prolonged skin bleeding time (p less than 0.001) in the fish oil group compared to the placebo group. Haematocrit, plasma viscosity, fibrinogen concentration, platelet count, and in vitro platelet aggregation were unaltered. No significant symptomatic or objective improvement was noted in angina pectoris in either group despite the significant rheological changes produced in the patients receiving fish oil. PMID- 2188795 TI - The treatment of mixed affective disorders in general practice: a comparison of trazodone and dothiepin. AB - The efficacy and tolerance of trazodone in the treatment of mixed affective disorder was compared with that of dothiepin in a double-blind, parallel group study in 228 general practice patients at 10 centres. After satisfying entry criteria, patients were randomized to receive either 150 mg trazodone at night, or 75 mg dothiepin at night for a 6-week period. Efficacy was assessed using the Hamilton Rating Scales for Depression and Anxiety. Significant improvements were observed in the condition of patients in each of the two treatment groups during the 6-week treatment period (p = 0.0001), with no statistically significant difference between the groups. There were no marked differences between the two treatment groups in the type of side-effects reported in response to open questioning, although a higher percentage of symptoms in the trazodone group were mild compared to the dothiepin group, and a lower percentage were severe. The incidence side-effects recorded by means of a checklist of common psychotropic side-effects was similar for the two treatment groups: dry mouth and drowsiness were the most frequent. A slightly higher proportion of patients withdrew from the dothiepin group, and of those who withdrew a higher percentage was due to side-effects than in the trazodone group. PMID- 2188797 TI - A double-blind comparison of oral amitriptyline and low-dose intramuscular flupenthixol decanoate in depressive illness. AB - Fifty-seven hospital out-patients with depressive symptoms were studied in a double-blind manner for up to 4 weeks, 30 whilst being treated with intramuscular flupenthixol decanoate (5 to 10 mg/fortnight) and 27 with oral amitriptyline (75 to 150 mg/day). The results of assessment using the Hamilton Rating Scale for Depression, the Leeds Self-Rating Scale for Depression and the Clinical Global Impressions severity scale showed that both therapies were effective in resolving depression in the patients studied. The two treatments were well tolerated and side-effect profiles were similar, dry mouth, faintness/dizziness and drowsiness being the most frequently reported adverse events. Extrapyramidal signs were seen in similar numbers of patients in each treatment group. One patient from each of the two groups was withdrawn from therapy before the end of the study because of adverse events. PMID- 2188796 TI - Cefetamet pivoxil in acute pyelonephritis: an open study. AB - Fifty-five adult patients with acute uncomplicated pyelonephritis were investigated in an open, prospective, randomized comparative study in which 31 patients were allocated to receive 1000 mg cefetamet pivoxil twice daily (or 2000 mg once daily) and 24 to receive 1000 mg cefadroxil twice daily, given orally for 10 to 15 days. Both groups were comparable for age, sex and body weight. Clinical signs and symptoms, i.e. flank tenderness, dysuria, urgency and pyuria, subsided somewhat more rapidly with cefetamet pivoxil, while defervescence was obtained by Day 3 +/- 1 in both groups. Twenty-nine of the cefetamet pivoxil patients were assessed bacteriologically. The pathogens isolated prior to treatment were E. coli (22), Proteus mirabilis (5), P. vulgaris (1) and P. stuartii (1). All 29 patients had sterile urine at treatment end. In the 22 assessable patients in the cefadroxil group, the pathogens isolated before treatment were E. coli (17), P. mirabilis (3), and K. pneumoniae (2). Six patients had relapsed at treatment end (5 E. coli and 1 P. mirabilis). Patients were re-assessed at follow-up, usually 2 to 4 weeks after the end of treatment. Four of the 29 patients in the cefetamet pivoxil group showed relapse (3 E. coli and 1 P. mirabilis) as did a further 3 in the cefadroxil group (2 E. coli and 1 P. mirabilis). The overall therapeutic outcome was considered as successful, i.e. cure or improvement, in 89.7% of the cefetamet pivoxil patients and 72.7% of those who had received cefadroxil. Tolerability was satisfactory for both trial drugs and there were only a few mild to moderately severe adverse events reported.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188798 TI - Long-term treatment of hypertension in the elderly with a combination of atenolol and nifedipine. AB - The efficacy and tolerability of a once-daily, fixed combination of 50 mg atenolol and 20 mg nifedipine slow release were evaluated in a 12-month open study of 27 elderly hypertensives who were either newly presenting patients or were those who were inadequately controlled on previous monotherapy or had unacceptable side-effects with their current therapy. After 1-month's therapy with the combination, the mean sitting blood pressure 1 to 4 hours post-dose decreased from 176/103 mmHg to 146/83 mmHg and was maintained at this level for the remainder of the study. Eight patients complained of side-effects on study entry. Sixteen had complaints at some time during the 12 months of fixed combination treatment and 4 were withdrawn because of side-effects. Dizziness occurred in 6 patients on the combination but, as with side-effects overall, tended to resolve with time; its occurrence did not appear to correlate with the on-treatment blood pressure. In this group of elderly hypertension patients, therefore, the combination therapy with atenolol plus nifedipine slow release appeared to exert a greater antihypertensive effect compared with previous therapy, which included atenolol alone, with no evidence of tachyphylaxis and was reasonably well-tolerated over a 12-month period. PMID- 2188799 TI - Histaminergic regulation of prolactin secretion. AB - Histamine (HA), which acts as a neurotransmitter in the central nervous system, participates in the neuroendocrine regulation of prolactin (PRL) secretion. HA has a predominant stimulatory effect which is mediated via H2-receptors following central administration and via H1-receptors following systemic infusion of the amine. In addition, HA seems to exert a minor inhibitory effect on PRL secretion, an effect unmasked only during blockade of the receptor mediating the stimulatory effect. Following central administration the inhibitory effect is mediated via H1 receptors, while following systemic administration this effect is mediated via H2 receptors. In accordance with these findings, the H2-receptor antagonist cimetidine (CIM) has an inhibitory (following central administration) or stimulatory (following systemic administration) effect on PRL secretion. However, high doses of CIM possess an additional PRL stimulatory action not related to blockade of H2-receptors. This non-specific action is not exerted by the chemically different H2-receptor antagonist ranitidine. Since HA has no effect directly at the pituitary level, the actions of the amine may occur at different sites within the hypothalamus by an effect on hypothalamic transmitters regulating PRL secretion. Dopaminergic as well as serotoninergic neurons are involved in the mediation of the action of HA, since the dopamine (DA) concentration in the pituitary portal vessels is decreased by central or systemic infusion of HA, and since blockade of DA synthesis and of DA or serotonin (5-HT) receptors inhibit or prevent the PRL stimulatory action of HA infused centrally or systemically. However, other factors regulating PRL secretion (e.g. beta endorphin, vasoactive intestinal peptide, vasopressin or TRH) may be involved in the mediation of the PRL response to HA. In men the effects of HA on PRL secretion are similar to the effects in male rats. Systemic infusion of HA stimulates PRL secretion via H1-receptors and inhibits PRL secretion via H2 receptors. The PRL-stimulatory effect of HA is caused by an inhibition of the dopaminergic system, while the PRL-inhibitory effect of HA may involve other transmitters than DA. In contrast to its stimulatory effect in men, HA had no effect on basal PRL secretion in women, but enhanced the PRL response to TRH. In rats or in humans the PRL stimulatory effect of HA is not caused by the cardiovascular actions of the amine.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2188800 TI - Cerebral blood flow in mechanically ventilated, preterm neonates. PMID- 2188801 TI - Monitoring of genotoxic exposure of humans by the sister chromatid exchange test. Methodology and confounding factors. AB - During the last decades several in vitro assays for measurement of genotoxic exposure have been developed. Exposure of humans to genotoxic products in their workplaces and the environment may be evaluated by means of the sister chromatid exchange test (SCE), which visualize exchange of DNA material between sister chromatids of a chromosome. This thesis deals with the development of SCE methodology and screening of confounding factors to make the method useful in population monitoring of genotoxic exposure of chemicals in vivo. Human lymphocytes are cultured under standardized conditions. The cells are prepared for chromosome analysis by means of new-developed apparatuses treating 12 samples simultaneously. By this method the preparation is speeded up and breathing of glacial acetic acid is minimized. Slides are prepared and stained. The staining procedure includes irradiation of the slides with long wave UV light. The light source has been optimized with regard to simplicity and spectral distribution to fit the absorption spectrum of the dye bisbenzimid. The irradiation time and dose to produce distinct harlequin stained chromosomes has been found. Population screening demands analysis in microscope of a great number of chromosomes. The working time at microscope is long and improvement of ergonomics and automation to speed up the procedure was obtained by development of a special microscope which projects the picture of SCEs at table level. The scanning table was motorized. These changes gave excellent ergonomic proporties as fixed positions of the eyes and hands were avoided. The system is fast and flexible and may semiautomatically produce karyotypes. By pointing out SCEs the system automatically registers SCE number, cell coordinates, mitosis quality and perform statistics. The statistical model which best describe the distributions of SCE data has been analysed. This was a negative binomial distribution, which is close to the Poisson distribution. The transformation y = (S).5 + (S + 1).5 follows a normal distribution. Variances of the transformation of the sum of SCEs in 30 cells within subjects and between subjects have been calculated, and on that basis the demands to sample size have been calculated. To avoid to make false statements about a connection between an exposure and SCE a detailed knowledge of confounding factors is essential. Of endogenous factors gender, age, race, and heredity have been considered. Of these gender and age contribute to the variation in SCE. Very high SCE level has been found in healthy members of a family and such cases have to be excluded from exposure studies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2188802 TI - Kinetic models for insulin disappearance from plasma in man. AB - The general use of first order kinetics to describe the disappearance of insulin from plasma in man contrasts the available evidence of saturation kinetics for insulin. In order to bridge this gap, we have put forward three alternative models of insulin kinetics. Model 1 considers the combined existence of first order and saturation (Michaelis-Menten) kinetics. Model 2 considers saturation kinetics alone. Model 3 considers first order kinetics alone. The validity of the models was studied in normal and type I (insulin-dependent) diabetic subjects. Sequential constant intravenous infusions of insulin at different rates were used to achieve different levels of steady state plasma insulin concentrations, while the glycaemic level (usually normoglycaemia) was maintained by a glucose clamp. Appropriate validation procedures demonstrated that the model of saturation kinetics alone (model 2) was superior to the other models in normal subjects at physiological and supraphysiological plasma insulin concentrations, and in diabetic patients at supraphysiological concentrations. The minimal model at physiological insulin concentrations in type I diabetic patients was that of first order kinetics (model 3). The kinetics of insulin was independent of the species of insulin (human or porcine) in both study groups. The actual glycaemic clamp level (normoglycaemia and moderate hyperglycaemia) did not influence the insulin disappearance rate. Binding of insulin to its receptor is considered to be the initial step in insulin degradation. Saturation kinetics of insulin may therefore be influenced by the saturation of binding of insulin molecules to their receptors. We found values of Km (i.e. the concentration of plasma insulin at which the insulin disappearance rate is half maximal) in normal subjects comparable to values of Kd (i.e. the dissociation constant for insulin-receptor binding) from receptor studies in isolated cells. Changes in regional (hepatic and/or renal) blood flow at hyperinsulinaemia represent an alternative explanation to a model of saturation kinetics. Increases in Vmax (i.e. the maximal insulin disappearance rate) and Km with increasing insulin dose were observed in normal subjects. This finding suggests that insulin may disappear from plasma by more than one saturable pathway. Additional studies are needed to confirm this observation. The clearance rate of insulin at infinitesimal plasma insulin concentrations (Vmax/Km) was 28 +/- 8 ml.kg-1.min-1 in normal subjects. This value is higher than most clearance rates previously reported in studies using first order kinetics. The clearance rate of insulin in type I diabetic patients was 20 +/- 4 ml.kg-1.min-1, corresponding to a reduction in clearance of 30% compared to normal subjects.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2188803 TI - Decidual prolactin. Studies of decidual and amniotic prolactin in normal and pathological pregnancy. PMID- 2188804 TI - The antimicrobial activity of psychotherapeutic drugs and stereo-isomeric analogues. AB - The aim of the investigation was to throw light on the question whether drugs other than antibiotics and chemotherapeutic agents exert an antimicrobial effect. In order to elucidate this, the antimicrobial effect of selected psychotherapeutic drugs and their stereo-isomeric analogues was studied. The development of psychotherapeutic drugs from aniline dyes has been reviewed against the background of its history considered as a scientific idea. It is demonstrated that psychotherapeutic drugs have an antimicrobial effect. Psychotherapeutic drugs show antimicrobial activity at high concentrations. Stereo-isomeric analogues of known psychotherapeutic drugs also have an antimicrobial effect. The selectivity of the various stereo-isomeric compounds depends on which microorganism and which chemical compound is investigated. Synergism is found between psychotherapeutic drugs (CPZ) and penicillin in vitro, and between a non-neuroleptic stereo-isomeric compound trans-CPT and penicillin in vivo, using infected mice as material. The antibacterial activity of psychotherapeutic drugs is independent of the antihistaminic, antihypersecretory, neuroleptic and antidepressant effect of these drugs. The examples chosen of investigations of the antimicrobial effect of psychotherapeutic drugs in vitro and in vivo lead to the conclusion and to the perspectives in the present study. Namely, the need for a general theory of the interplay between host organism, microorganisms and drugs. This proposition is based on a concern to argue against the view that the prokaryotic effect of eukaryote-directed drugs is without major significance, either for scientific research or for clinical treatment. PMID- 2188805 TI - Developmental outcome of minority infants: a process-oriented look into our beginnings. AB - This article reviews the literature on the development of children of minority status from birth to 3 years of age (infants). 5 major sources of influence on the developmental outcome of minority infants are proposed: cultural beliefs and caregiving practices, health status and health care practices, family structure and characteristics, socioeconomic factors, and biological factors. It is suggested that differences exist between minority and Anglo families in their developmental goals and interactions during the infancy period. The health status of some minority groups places these infants in an at-risk category for neurodevelopmental problems. The family context is characterized by younger mothers, a higher percentage of single heads of households, but also large, extended families. Socioeconomic factors have a pervasive influence on both infants and parents, and the contribution of biological factors is suggested but poorly understood. It is concluded that these factors act synergistically to place these infants in alternative (not necessarily deviant) developmental pathways, or in "at-risk" categories for neurodevelopmental problems, while canalization processes are operating to insure that major developmental milestones are achieved. PMID- 2188806 TI - The impact of economic hardship on black families and children: psychological distress, parenting, and socioemotional development. AB - Family processes affecting the socioemotional functioning of children living in poor families and families experiencing economic decline are reviewed. Black children are of primary interest in the article because they experience disproportionate shares of the burden of poverty and economic loss and are at substantially higher risk than white children of experiencing attendant socioemotional problems. It is argued that (a) poverty and economic loss diminish the capacity for supportive, consistent, and involved parenting and render parents more vulnerable to the debilitating effects of negative life events, (b) a major mediator of the link between economic hardship and parenting behavior is psychological distress deriving from an excess of negative life events, undesirable chronic conditions, and the absence and disruption of marital bonds, (c) economic hardship adversely affects children's socioemotional functioning in part through its impact on the parent's behavior toward the child, and (d) father child relations under conditions of economic hardship depend on the quality of relations between the mother and father. The extent to which psychological distress is a source of race differences in parenting behavior is considered. Finally, attention is given to the mechanisms by which parents' social networks reduce emotional strain, lessen the tendency toward punitive, coercive, and inconsistent parenting behavior, and, in turn, foster positive socioemotional development in economically deprived children. PMID- 2188807 TI - Toward cultural/ecological perspectives on schooling and achievement in African- and Asian-American children. AB - The review acknowledges that research on the family and its contribution to achievement in ethnic minority children is important. Past research and theorizing suggest the need for new directions, however. For example, research in educational achievement predicts educational failure for African-American students and educational success for Asian-American students. Little differentiation is made either among African-Americans or among Asian-Americans of different cultural, language, immigration, and economic backgrounds. The theory and design of research on family and educational achievement have been influenced by prevailing societal stereotypes. Research and policy implications of this review include the need to move toward cultural/ecological theories of achievement socialization and development. PMID- 2188808 TI - [Peripheral aneurysms]. PMID- 2188809 TI - [Aorto-iliac artery aneurysm]. PMID- 2188810 TI - [The thoraco-abdominal aortic aneurysm]. PMID- 2188811 TI - [Two-stage rupture of the infrarenal vena cava following polytrauma]. PMID- 2188813 TI - [Aneurysma verum of the left renal vein as an incidental surgical finding]. PMID- 2188812 TI - [Recurrent hemobilia caused by a ruptured pseudoaneurysm of the cystic artery in the gallbladder]. PMID- 2188814 TI - [Pioneers in skin transplantation in Austria and Germany in the 19th century]. PMID- 2188815 TI - Effect of focus on cell detection and recognition by the Cell Analyzer. AB - The effect of defocusing on the quality of signals from live cells detected by an automated image cytometry device, the Cell Analyzer, was examined. The influence of these effects on the ability of this device to automatically locate cells plated into a tissue culture flask was then determined by measuring the performance of cell detection and recognition procedures as a function of focus setting. Acceptable limits for deviation from the optimal focus setting (as determined by microscope objective position) were found to be similar for both these procedures, ranging from 40 microns below to 25 microns above the optimal focus position. These limits were asymmetrical about ideal focus due to a pronounced asymmetry in the effects of positive and negative defocusing on the cell signal. PMID- 2188816 TI - Detection of S cells and evaluation of DNA denaturation protocols by image cytometry of fluorescent BrdUrd labelling. AB - This paper addresses the problem of detecting weak incorporation of BrdUrd and the related efficiency of the denaturation protocols used to unmask this thymidine analog. Evidence is presented that measuring the distribution of BrdUrd tagged fluorescence intensities by image cytometry generates a standard deviation threshold that discriminates between positive and negative MRC5 cells in vitro. A comparison of the thresholding by standard deviation (SDT) with the usual thresholding by the nuclear total fluorescence intensity (FIT) demonstrated that SDT has a significantly higher sensitivity (99.4-100%, depending on the denaturation protocols) than FIT (94.7 and 74.3%, respectively), although both tests have a high specificity (93% and 100%, respectively) for detecting S cells. Since detecting the S cells is not only dependent on the test used, but also on the denaturation protocols, a quality index (QI) was derived from the standard deviation and the mean value of the non-specific fluorescence of negative cell population versus BrdUrd fluorescence of positive cell population. The following DNA denaturation protocols have been assessed according to QI: acidic denaturation, thermal denaturation in formamide, and thermal denaturation in distilled water. Each denaturation procedure was preceded or not by incubation in either proteinase K or Triton X-100. The results showed that thermal denaturation in formamide, especially when preceded by proteinase K incubation, revealed the largest difference between negative and positive cells. This work also demonstrated that image cytometry of BrdUrd-labelled cells can be suitable for clinical application because of the high sensitivity provided and the small samples needed. PMID- 2188817 TI - An improved flow cytometric assay for somatic mutations at the glycophorin A locus in humans. AB - An improved method has been developed for the glycophorin A assay for somatic cell mutations in humans. The new assay, named the "BR6" assay, can be performed on a commercially available, single-beam flow cytometer, in contrast to the previously described 1W1 assay that required a dual-beam flow sorter. A modified cell labeling method developed for the BR6 assay results in improved separation of normal and mutant phenotype cells, as well as eliminating some cellular artifacts that affected the 1W1 assay. Parallel measurements on samples from 17 normal donors showed that the BR6 assay yields comparable variant cell frequencies and improved measurement precision compared with the 1W1 assay. A detailed analysis of three individuals who showed large differences in background variant frequency with the 1W1 assay confirmed that these differences could also be detected with the BR6 assay. A dramatically elevated variant cell frequency was seen with the BR6 assay of an individual exposed to a high level of ionizing radiation in an accident at Goiania, Brazil. PMID- 2188818 TI - Analysis of c-erbB-2 protein expression in conjunction with DNA content using multiparameter flow cytometry. AB - Breast cancer is a leading cause of cancer death among women. Factors useful for determining the prognosis of breast cancer include axillary lymph node involvement, tumor size, hormonal receptor status, nuclear grade, and relative DNA content. The c-erbB-2 protooncogene is amplified in 10-40% of primary breast tumors, as well as in breast cancer cell lines; where it is amplified there is increased expression of its product. We have investigated the DNA content and c erbB-1 protein expression in tumor cell lines and in breast cancer patient specimens by multiparameter flow cytometry. The study was enabled by the discovery that both cellular integrity and c-erbB-2 antigen reactivity were preserved in cells and tissues following fixation in 70% ethanol. We demonstrate that flow cytometric analysis of c-erbB-2 expression in populations of ethanol fixed tumor cells is a reliable and sensitive quantitative method that correlates well with previously documented semiquantitative techniques. This is a feasible method for analyzing archived clinical samples, and further allows correlations between c-erbB-2 levels and other cellular parameters. Additionally, this method detects abnormal populations not identified by DNA content analysis alone. Further studies utilizing this approach are necessary to evaluate the prognostic value of this oncoprotein in human breast cancer. PMID- 2188819 TI - Liver transplantation. Initial experience in the Veterans Administration. AB - The Veterans Administration entered the clinical liver transplant field in 1983 and continued its program through July 1988. During this time interval, from the 172 Veterans Administration Medical Centers in the United States, 146 contact calls were initiated to the single center authorized to do liver transplants for the Veterans Administration. One hundred one (69%) of these contact calls resulted in a patient evaluation. Of the 101 patients evaluated, 77 (76%) were accepted for liver transplantation (OLTx). Of these 77, 67 (87%) were transplanted. The reasons for denial of transplant evaluation were numerous and included metastatic cancer, active alcoholism, homosexuality, and a variety of concurrent medical problems. The reasons for denying liver transplantation after evaluation were similar and included concurrent medical problems that contraindicated transplantation (N = 14), metastatic cancer (N = 6), and liver disease of insufficient severity to justify transplantation (N = 3). The number of transplants performed annually by the Veterans Administration increased from one in 1983 to 21 in 1988. Seventeen second grafts and two third grafts were transplanted in 17 cases, resulting in a retransplant rate of 22%; 46% of the patients receiving a second graft survived. None of those receiving three grafts survived. The reasons for retransplantation included acute and/or chronic rejection (N = 6), hepatic artery thrombosis (N = 5), primary graft failure (N = 4), recurrent cancer (N = 2), fulminant hepatitis and portal venous emboli (one each). A total of 45 transplanted patients are still alive (67% of those transplanted).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188820 TI - Prevalence of gallstones in patients with primary immunoglobulin deficiency. Evidence for lack of association. AB - In the early 1970s an increased prevalence of gallstones was reported in adults and children with immunoglobulin deficiency. As the advent of ultrasonography has largely changed the diagnostic approach to gallstones, we have reevaluated the prevalence of cholelithiasis in a group including 37 patients with common variable immunodeficiency and seven patients with other forms of primary immunodeficiency. All patients were receiving intravenous gammaglobulin replacement since 1983 or, in more recent cases, soon after the diagnosis was made, and therefore had relatively few infections. All patients underwent a hepatobiliary ultrasonogram and blood sampling. Data were compared, after age and sex standardization, with those obtained by the GREPCO in a free-living population of 1239 men and 1081 women. Only two women with immunoglobulin deficiency had gallstones. One of these was obese and had had one pregnancy. Both were asymptomatic. None of the patients studied had a history of cholecystectomy or evidence of biliary sludge. Thus, the observed prevalence rates of gallstone disease were 8.7% in women and 0% in males, respectively, against expected values of 9.5% and 3.2%. Immunodeficient patients expressed several putative risk factors for gallstones in the low range (body mass index, total and HDL cholesterol, and blood glucose in both sexes, and triglycerides in men). We conclude that gallstone disease is not more frequent in patients with immunodeficiency syndromes undergoing immunoglobulin therapy than in the general population. PMID- 2188821 TI - Plasma pancreastatin responses after intrajejunal infusion of liquid meal in patients with chronic pancreatitis. AB - The plasma concentrations of pancreastatin and cholescystokinin (CCK), exocrine pancreatic responses, and gallbladder contraction following intrajejunal ingestion of 100 kcal/hr semidigested liquid meal (Clinimeal) were simultaneously studied in six controls and six patients with chronic pancreatitis. An intrajejunal infusion of Clinimeal resulted in significant rises of pancreastatin and CCK, which paralleled the pancreatic secretion and gallbladder contraction. On the other hand, an intrajejunal infusion of Clinimeal resulted in a delayed rise of pancreastatin and no rise of CCK in chronic pancreatitis. Pancreatic secretion did not increase, and gallbladder contraction was not induced in these patients. It is suggested that pancreastatin may play an important role in the regulation of intestinal phase of exocrine pancreas. The impaired pancreastatin and CCK release in chronic pancreatitis may be due to the inappropriate stimuli in the lumen, which is attributed to pancreatic exocrine dysfunction, or to disturbed physiological regulation between the pancreas and gastrointestinal tract. PMID- 2188822 TI - Importance of the renin-angiotensin-aldosterone system (RAS) in the physiology and pathology of hypertension. An overview. AB - Current leading theories of the mechanisms of essential hypertension include the participation of the renin-angiotensin-aldosterone system (RAS). Recent advances provide means for a critical reassessment of this system in the physiology and pathology of hypertension. The expression of the proteins of the RAS in organs other than the kidneys suggests that angiotensin II also acts as a modulator of cell function. This paper discusses the role of tissue angiotensin peptides in the regulation of blood pressure and suggests new ideas with regard to the importance of the brain RAS in the development of essential hypertension. PMID- 2188824 TI - Angiotensin-converting enzyme (ACE) inhibition. Therapeutic option for diabetic hypertensive patients. AB - When choosing antihypertensive agents for the treatment of diabetic patients with hypertension, it is necessary to consider the individual characteristics of these patients. In this respect, angiotensin-converting enzyme (ACE) inhibitors constitute an attractive option for diabetic patients. The effects of enalapril alone for 16 weeks in 23 non-insulin-dependent diabetic (NIDD) patients and in 10 non-diabetic patients with mild to moderate essential hypertension (EH) [diastolic blood pressure greater than 95 mm Hg and less than 115 mm Hg] were evaluated. Similar reductions in both systolic and diastolic blood pressure were observed in 17 NIDD patients (from 155 +/- 18/100 +/-11 mm Hg to 128 +/- 12/82 +/ 8 mm Hg, respectively) and in 6 EH patients (from 155 +/- 21/100 +/- 6 mm Hg to 125 +/- 20/84 +/- 8 mm Hg, respectively) who achieved and maintained blood pressure control (diastolic blood pressure less than 90 mm Hg) for 16 weeks. In 4 NIDD and 4 EH patients blood pressure was not controlled. Two NIDD patients discontinued the medication, one because of symptomatic postural hypotension and the other, who had a plasma creatinine level of 1.8 mg/dl, because of hyperkalaemia (K = 6.1 mEq/L). In the responders, enalapril did not alter glucose tolerance, plasma or urinary excretion of creatinine, potassium, sodium and aldosterone. Plasma renin activity increased in the NIDD group only. In 11 patients (6 NIDD and 5 EH), the elevated protein or albumin excretions decreased. It is concluded that enalapril is a good therapeutic option for NIDD patients with hypertension. PMID- 2188823 TI - Angiotensin-converting enzyme inhibitors in chronic renal failure. AB - In contrast to some other antihypertensive drugs, angiotensin-converting enzyme (ACE) inhibitors lower glomerular capillary pressure, decrease proteinuria, and may halt progressive glomerular injury and loss of renal function in experimental chronic renal failure (CRF). Although these favourable effects of ACE inhibition may result from alterations in glomerular haemodynamics, there is some evidence to show that ACE inhibitors may reduce glomerular injury through other mechanisms. CRF in man may result from a variety of insults to the kidney. However, it is not known whether, or under which conditions, glomerular capillary pressure is elevated in this heterogeneous population. Limited data suggest that renal haemodynamics (and perhaps glomerular capillary pressure) may depend in part on the level of systemic blood pressure. In addition, several studies have demonstrated a positive correlation between systemic blood pressure and the rate of progression of CRF. ACE inhibitor therapy generally lowers systemic blood pressure, does not alter renal function and decreases proteinuria in patients with CRF. The reduction in proteinuria appears to be variable and may depend on pretreatment glomerular haemodynamics and/or the activity of the renin angiotensin-aldosterone system. Preliminary evidence also suggests that ACE inhibitors may slow the progression of renal disease in humans with CRF. However, this effect, like the reduction in proteinuria, has not been observed consistently in all patients. In addition, it is not clear whether these effects on proteinuria and progression of disease are unique to ACE inhibitor therapy, since the lowering of systemic blood pressure with other drugs may have similar effects. The heterogeneity of the response to ACE inhibition suggests that there may be interpatient differences in glomerular haemodynamics in CRF, perhaps related to systemic blood pressure or the underlying disease process. Studies to date indicate that ACE inhibitors exert their beneficial effect by lowering glomerular capillary pressure and that not all patients will benefit from therapy with regard to proteinuria or amelioration of disease progression. However, further investigation of the haemodynamic and non-haemodynamic effects of ACE inhibitors, as well as the variability of response, may ultimately allow the selection of those patients who would benefit from such therapy. PMID- 2188825 TI - Antihypertensive therapy. Is it different in the elderly? AB - Pathophysiological mechanisms of pressure elevation are different in the elderly hypertensive patient than in middle-aged or young patients. The elderly patient is characterised by a decrease in cardiac output, renal blood flow, and intravascular volume and an increase in total peripheral resistance and vascular resistance. Elderly patients also, quite often, have target organ disease such as left ventricular hypertrophy and nephrosclerosis. Because of impaired baroreflexes and latent or overt cerebrovascular disease, the elderly patient is particularly susceptible to abrupt falls in arterial pressure. Clearly, these physiological findings have to be taken into account when prescribing antihypertensive therapy. Calcium channel blockers and converting enzyme inhibitors seem to be particularly useful in the geriatric population. A close match between the underlying pathophysiology of pressure elevation in a given patient and the pharmacological effects of a selected antihypertensive drug will provide more rational and convenient control of arterial pressure in our senior citizens. PMID- 2188826 TI - Comparative efficacy and safety of enalapril and sustained-release nifedipine in patients with mild to moderate hypertension. The Enalapril vs Nifedipine French Study Group. AB - The long acting angiotensin-converting enzyme inhibitor enalapril was compared with the calcium channel blocker nifedipine as sustained-release formulation in 136 patients with mild to moderate hypertension. This multicentre study was carried out in a double-blind, double-dummy fashion by 28 cardiologists in private practice. After a 2-week placebo period, patients were randomly allocated to 2 treatment groups; the first group received enalapril 20 mg daily (n = 68), and the second group received sustained-release nifedipine 20 mg twice daily (n = 68). The duration of treatment was 12 weeks. In both groups, hydrochlorothiazide 25 mg was added at week 4 if diastolic blood pressure remained greater than 90 mm Hg. At week 8, if the target diastolic pressure of less than 90 mm Hg was not achieved, the dosage of hydrochlorothiazide was increased to 50mg. The clinical characteristics of the patients in each group were comparable. After 4 weeks of treatment, the reduction in supine diastolic blood pressure was similar in both groups (12.1 mm Hg in the enalapril group vs 10.3 mm Hg in the nifedipine group). Moreover, although the difference between the groups was more noticeable after 12 weeks of treatment (16.3 vs 13.9 mm Hg, respectively), it did not reach significance. The number of patients experiencing clinical adverse effects was significantly greater in the nifedipine group than in the enalapril group [33 (48.5%) vs 18 (26.5%), respectively]. The most common complaints of patients administered nifedipine included swollen ankles, flushing and headaches, whereas complaints in the enalapril group included cough, asthenia, and epigastralgia. Three patients were withdrawn from the study because of side effects in the enalapril group and 10 were withdrawn from the nifedipine group. These results indicate that enalapril and sustained-release nifedipine are equally effective in controlling mild to moderate hypertension. However, enalapril was much better tolerated in this study. PMID- 2188827 TI - A cooperative study to evaluate the efficacy and safety of enalapril in Puerto Rican patients with mild to moderate hypertension. AB - The efficacy and safety of enalapril and its effects on the quality of life were evaluated in 1017 Puerto Rican patients with uncomplicated mild to moderate essential hypertension. Enalapril was administered for 4 weeks in an open label, noncomparative study. Initially, patients received enalapril 5 mg and the dosage was titrated upwards, according to response, to a maximum of 20 mg/day. The goal of therapy was to achieve a diastolic blood pressure (DBP) less than 90 mm Hg. The study included 468 male and 545 female patients (mean age 52.6 +/- 11.9 years). A subgroup of 294 elderly patients was also evaluated (mean age 65.9 +/- 6.1 years). Mean blood pressure decreased from 157/99 mm Hg to 138/84 mm Hg (p less than 0.0001) in 966 patients who received enalapril as monotherapy. Mean blood pressure decreased from 164/99 mm Hg to 143/85 mm Hg (p less than 0.0001) in the elderly patients. After 4 weeks of enalapril monotherapy, 67% of the patients had a DBP less than 90 mm Hg. Enalapril was very well tolerated. Headache and dizziness were the most frequently reported side effects. Among the patients who completed a quality of life questionnaire, more than 70% reported feeling the same or better and less than 2% reported feeling worse after enalapril therapy. In conclusion, enalapril seems to be an excellent alternative as initial therapy in young and elderly Puerto Rican hypertensive patients. PMID- 2188828 TI - [Effects of prostaglandins on the activity of natural killer cells during tumor growth]. AB - Prostaglandins (PG) are studied for their effect on the activity of natural killer cells (NKC) under the tumour growth. The interaction of PG with other regulators of the NKC activity (interferons, interleukins) is considered. PMID- 2188829 TI - [Surface membrane antigens and receptors of the Reed-Sternberg and Hodgkin's cells in lymphogranulomatosis]. AB - The results obtained provide evidence concerning the nature of the Hodgkin and Reed-Sternberg cells. The data based on application of new methods developed during last years such as different enzymo- and immunocytochemical techniques, monoclonal antibody and lectin application and molecular studies of gene rearrangement are presented. PMID- 2188830 TI - [Electron microscopy morphometry of cells of patients with different immunologic subvariants of acute lymphoblastic leukemia]. AB - By the electron-microscopic morphometry it is determined that the cells of acute lymphoblastic leukemia (ALL) with synonymous immunological phenotype also have the same submicroscopic structure and are characterized by definite morphometric features which distinguish them from lymphoblasts of other subvariants. These results indicate that the electron-microscopic morphometry is one of the criteria for precise identification of leukemic cells. Besides, the similarity of the morphometric features of leukemic cells of the concrete lineage with the synonymous differentiation status confirm their lineage fidelity. PMID- 2188831 TI - Progesterone and estradiol plasma levels in neonatally irradiated cycling rats. AB - Female rats which were exposed to a single low dose of gamma irradiation (6R or 15R) at the age of 8 days produce smaller litters when mature than untreated controls. The possibility that the impaired fertility resulted from altered ovarian activity as reflected by changes in plasma levels of progesterone or estardiol was investigated. Plasma levels of both steroids were determined throughout the day of proestrus. Progesterone level was also determined in 6R animals on the day of weaning. The maturity of such irradiated rats was assessed by observing the time of vaginal opening. The results indicated that the preovulatory peak of progesterone was delayed in the 6R rats whereas in the 15R group its levels were significantly lower. On the other hand no differences in estradiol plasma levels were noticed between the groups. The higher level of progesterone in the 6R animals was not evident on the day of weaning and was even in both groups, but vaginal opening in the irradiated rats was significantly delayed. The elevated level of progesterone might be responsible, among other endocrine changes, for the lower fertility of neonatally irradiated mature female rats. PMID- 2188832 TI - Application of two-dimensional gel electrophoresis in the study of cytoskeletal protein regulation during growth activation and differentiation. AB - Two-dimensional gel electrophoresis was used to study the regulation of cytoskeletal protein synthesis during growth activation and development of the differentiated phenotype. We demonstrated a correlation between the state of organization and the expression of the respective cytoskeletal protein by showing that depolymerization of microtubules leads to a rapid decrease in new tubulin synthesis. We found that the synthesis of vimentin in both fibroblasts and epithelial cells correlates with extensive cell spreading on the substrate, while cytokeratin synthesis is maximal when cell to cell contacts are abundant. The analysis of cytoskeletal elements, involved directly in the formation of cell contacts, revealed that the level of vinculin synthesis is dependent on the extent of adherent type of cell contacts formed. Moreover, we found that the transient disappearance of vinculin from adhesion plaques of quiescent fibroblasts in response to serum factors was followed by an induction of vinculin mRNA and protein synthesis. The morphological changes associated with establishment of the differentiated phenotype were also found to include changes in the expression of the cytoskeletal-extracellular matrix complex. This was demonstrated in several differentiating systems: in 3T3 preadipocytes which change their shape from a fibroblastic to a spherical shape when stimulated to differentiate with adipogenic medium, we observed a decrease in mRNA levels and in the synthesis of fibronectin, beta-integrin, and the microfilament proteins, vinculin, alpha-actinin, tropomyosin and actin. The culturing of these cells on a certain extracellular matrix prevented the morphological changes occurring in the presence of adipogenic medium and blocked the shifts in cytoskeletal- and differentiation-related gene expression. Similar changes in the organization and expression of cytoskeletal proteins were identified during maturation of primary ovarian granulosa cell cultures, stimulated with gonadotropic hormones to form highly steroidogenic cells. The cell rounding and aggregation occurring during this process were associated with a decreased synthesis of vinculin, alpha actinin, actin and the nonmuscle tropomyosins. The physiological relevance of these changes was suggested by the observation that the level of tropomyosin mRNA was lower in follicles of animals at late stages of granulosa cell maturation when compared to earlier stages. The expression of tissue-specific and cytoskeletal proteins was also determined in primary cultures of liver hepatocytes, maintained under conditions either favorable for growth or for expression of liver-specific functions. When DNA synthesis was elevated, cytoskeletal protein synthesis was high and that of liver-specific proteins was low.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2188833 TI - The analysis of glycoproteins in cells and tissues by two-dimensional polyacrylamide gel electrophoresis. AB - Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) was used to identify and analyse subsets of proteins in cells and tissues. The combination of 2-D PAGE and [125I] concanavalin A overlay revealed an extraordinary complexity and diversity in the glycoprotein profiles of different cell types. However, the glycoproteins are not expressed idiosyncratically. Rather, their expression is closely linked to the state of differentiation of a particular cell type. Such glycoproteins can therefore be used to generate antibodies specific for differentiated cells. 2-D PAGE analyses of cellular glycoproteins also revealed a major common glycoprotein of 100 kDa. This was localised to the lumen of the endoplasmic reticulum and is referred to as endoplasmin. The combination of 2-D PAGE with electroblotting and 45Ca overlay revealed that endoplasmin and several other luminal endoplasmic reticulum proteins (reticuloplasmins) are high capacity, low affinity calcium binding proteins which could function as calcium storage proteins in the endoplasmic reticulum. One of these called calreticulin is also found in the sarcoplasmic reticulum. 2-D PAGE and 45Ca overlay has been used to demonstrate the presence of a calcium-binding protein (CP22/sorcin) in the cytosol of rodent multidrug resistant cells. Analyses of murine serum by 2-D PAGE revealed the presence of a novel stress protein serum amyloid P component. These studies illustrate the value of 2-D PAGE when used in combination with detection methods which select specific subsets of proteins such as glycoproteins. PMID- 2188834 TI - Protein synthesis initiation factor modifications during viral infections: implications for translational control. AB - Infection of tissue culture cells with certain viruses results in the shutoff of host cell protein synthesis. We have examined virally infected cell lysates using two-dimensional gel electrophoresis and immunoblotting to ascertain whether initiation factor protein modifications are correlated with translational repression. Moderate increases in eukaryotic initiation factor (eIF)-2 alpha phosphorylation are detected in reovirus- and adenovirus-infected cells, as reported previously (Samuel et al., 1984; O'Malley et al., 1989). Neither vesicular stomatitis virus, vaccinia virus, frog virus III, rhinovirus, nor encephalomyocarditis virus caused significantly increased 2 alpha phosphorylation. There were no reproducible, significant changes in eIF-4A, eIF 4B, or eIF-2 beta in cells infected by any of these viruses. The cleavage of eIF 4F subunit p220, such as has been previously demonstrated to occur in poliovirus (Etchison et al., 1982) and rhinovirus (Etchison and Fout, 1985), was not detected in any of the other virus infections analyzed. PMID- 2188835 TI - A two-dimensional gel protein database of noncultured total normal human epidermal keratinocytes: identification of proteins strongly up-regulated in psoriatic epidermis. AB - A two-dimensional (2-D) gel database of proteins from noncultured total normal human epidermal keratinocytes has been established. A total of 1449 [35S]methionine labelled proteins (1112 isoelectric focusing, 337 nonequilibrium pH gradient electrophoresis) were resolved and recorded using computer assisted (PDQ-SCAN and PDQUEST software) 2-D gel electrophoresis. By matching the protein patterns of total keratinocytes and transformed human amnion cells (master database; Celis et al., Leukemia 1988, 2, 561-602) as well as by 2-D immunoblotting and microsequencing of keratinocyte proteins, it was possible to identify 72 polypeptides in the keratinocyte database. The database also includes data on polypeptides that are synthesized at a higher level by keratinocytes enriched in basal cells, and on six secreted proteins which are produced, albeit at a reduced rate, by normal keratinocytes and that are strongly up-regulated in psoriatic epidermis (Celis et al., FEBS Letters, in press). PMID- 2188836 TI - Sympathetic activation in congestive heart failure. AB - This paper reviews the evidence that congestive heart failure is characterized by an increase in sympathetic nerve activity and that this may begin in an early symptomatic phase and progress with the severity of the disease. The sympathetic activation initially plays a compensatory role but eventually is outweighted by adverse consequences at both cardiac and vascular levels which may aggravate the clinical status and negatively affect prognosis. This is likely to depend on the fact that the sympathetic activation becomes excessive due to reduction in sensitivity of baroreflexes and cardiopulmonary reflexes restraining sympathetic tone (functional reflex denervation) and positive interactions between the sympathetic and the renin-angiotensin system. Therapeutic interventions may reduce the marked sympathetic activation which occurs in heart failure, and in some instances (particularly with digitalis compounds) may also improve the impaired sensitivity of reflex cardiovascular control. PMID- 2188837 TI - Sympathetic activity and regional blood flow in heart failure. AB - The syndrome of heart failure results from inappropriate sodium and water retention by the kidneys which results, at least in part, from changes in renal haemodynamics. Renal blood flow at rest in heart failure is reduced in proportion to the reduction in cardiac output and falls dramatically during exercise as the cardiac output is redistributed to the exercising muscles. Both these phenomena are associated with a rise in plasma noradrenaline concentration. Afferent arteriolar tone is partly controlled by alpha-adrenoceptor stimulation while stimulation of beta 2-receptors will stimulate renal release of renin; through the elaboration of angiotensin II, profound effects on extra- and intra-renal vascular tone can occur. Although alpha-adrenoceptor stimulation can result in coronary vasoconstriction and a fall in coronary blood flow in patients with heart failure due to underlying atheromatous coronary heart disease, increased myocardial oxygen demand as the result of beta 1 (and cardiac beta 2) simulation may be more relevant. The control of limb blood flow is of great importance symptomatically. The systemic vasoconstriction that typifies the severe heart failure state has been a target for many vasodilatory interventions including alpha 1-receptor blockade and beta 2-receptor stimulation. Unfortunately, there is little evidence that such treatment leads to any specific increase in muscle blood flow either at rest or during exercise. In severe heart failure, sympathetic activity is increased at rest leading to vasoconstriction in several vascular beds, while in milder heart failure, excessive sympathetic stimulation is evident only during exercise. In either circumstance, however, it is evident that certain advantages may accrue from modulation of this excessive sympathetic activity. PMID- 2188838 TI - Diastolic function and heart failure: an overview. AB - Diastolic dysfunction is being recognized increasingly as a primary cause of congestive heart failure. It may result from physiological abnormalities of myocardial relaxation, or anatomical abnormalities which increase resistance to ventricular inflow. With regard to physiological abnormalities, there is substantial evidence to indicate that myocardial ischaemia and hypertrophy are two conditions characterized by impaired inactivation and relaxation of myocardial cells. These conditions often co-exist in patients with idiopathic hypertrophic subaortic stenosis or calcific valvular aortic stenosis. Recent evidence also suggests a role for calcium overload in the diastolic dysfunction seen in some patients with advanced congestive heart failure. Diastolic dysfunction may be of fundamental importance in the pathophysiology of flash pulmonary oedema in patients with advanced ischaemic heart disease, since myocardial ischaemia in such patients may lead to a decline in relaxation rate, increased resistance to early diastolic filling and further impairment in diastolic coronary blood flow due to intramyocardial compression of capillaries and venules. During the transient ischaemia of angina pectoris, patients with multivessel coronary artery disease often show a striking upward shift in the left ventricular diastolic pressure-volume relationship, signifying a marked decrease in distensibility of the left ventricular chamber. With regard to anatomical abnormalities, diastolic dysfunction in heart failure may result from structural changes within the ventricular wall. Diastolic dysfunction of the left ventricle may result from extrinsic compression by pericardial effusion (tamponade), pericardial constriction, and right ventricular overload. Thus, a variety of physiological and anatomical abnormalities may lead to increased resistance to diastolic filling of one or both ventricles, resulting in diastolic heart failure. PMID- 2188839 TI - Changes in cardiovascular function with aging. AB - Overall cardiovascular function at rest in most healthy elderly individuals is adequate to meet the body's need for pressure and flow. The resting heart rate is unchanged. Heart size is essentially not different in younger vs older adults, but heart wall thickness increases modestly, due largely to an increase in myocyte size. While the early diastolic filling rate is reduced, an enhanced atrial contribution to ventricular filling in elderly individuals maintains filling volume at a normal level. Although systolic pressure at rest increases with age, the resting end-systolic volume and election fraction are not altered, due partly to the increase in left ventricular thickness. Physical work capacity declines with advancing age, but the extent to which this can be attributed to a decrement in cardiac reserve is not certain. Part of the age-related decline in maximum oxygen consumption appears to be due to peripheral rather than central circulatory factors, e.g. to a decrease in muscle mass with age during exercise, the ability to direct blood flow to muscles, and the ability of muscle to utilize oxygen. Some elderly individuals exhibit cardiac dilatation which produces an increased stroke volume sufficient to counter the well-known age-related decrease in exercise heart rate, such that high levels of cardiac output can be maintained during exercise. Still, in these individuals, the exercise-induced reduction in end-systolic volume and increase in ejection fraction is less than in younger individuals. A similar haemodynamic profile occurs in individuals of any age who exercise in the presence of beta-adrenergic blockade.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188840 TI - Diastolic dysfunction and myocardial energetics. AB - Myocardial relaxation is an energy-dependent process. Indeed, adenosine triphosphate (ATP) is required to pump free myoplasmic calcium back into the sarcoplasmic reticulum. It is also necessary to extrude the calcium ions which enter the cell during the plateau phase of the action potential. The calcium sodium exchange mechanism does not seem to require energy in itself, but sodium exchanged for calcium eventually needs to be extruded via sodium/potassium ATPase and there is also an ATP-dependent calcium pump. Thus, when ATP production is limited, calcium may remain fixed to troponin for part or for the whole of diastole, resulting in a slower rate of isovolumic relaxation and reduced distensibility of the myocardium. Alterations in diastolic function caused by inadequate energy production occur in the high-demand type of myocardial ischaemia. There is also growing evidence that most forms of heart failure are accompanied by a state of energy depletion. Alterations in mitochondrial density and enzymatic activity are common in the failing myocardium and may partially explain the reduction in ATP production. Inadequate growth of the capillary network in hypertrophied myocardium, impaired subendocardial perfusion due to increased diastolic wall stress and/or coronary artery disease, probably also contribute to an imbalance between energy production and utilization. As relaxation is intrinsically a much slower process than activation and since changes in ATP concentration may also affect calcium efflux by allosteric effects, impaired relaxation and reduced diastolic distensibility are almost universal in chronic congestive heart failure. Optimal therapy of heart failure should, therefore, also aim at improving this phase of the cardiac cycle. PMID- 2188841 TI - Diastolic function as a target of therapeutic interventions in chronic heart failure. AB - Although conventional wisdom holds that pharmacological interventions improve the haemodynamic and clinical status of patients with chronic heart failure by enhancing systolic performance, this hypothesis fails to explain many of the responses seen following the administration of these drugs. The observation that abnormalities of diastolic function are an earlier and more sensitive marker of heart failure than abnormalities of systolic function suggests that vasodilator and inotropic drugs may act primarily by improving diastolic function. This belief is supported by the following findings: (1) exercise capacity in chronic heart failure is more closely related to left ventricular filling pressure than to cardiac output or limb blood flow; (2) only drugs that lower left ventricular filling pressure have been shown to improve exercise capacity, whereas drugs that primarily increase cardiac output or left ventricular ejection fraction do not enhance effort tolerance; (3) the primary mechanism by which vasodilator and inotropic drugs lower left ventricular filling pressure is by exerting a favourable effect on left ventricular diastolic function rather than on left ventricular volume; (4) drugs that improve diastolic function tend to affect favourably the clinical status of patients with chronic heart failure, whereas drugs that adversely alter ventricular relaxation produce deleterious haemodynamic and clinical effects. These observations suggest that the diastolic abnormalities of heart failure may be an ideal target for the development of new therapeutic interventions. PMID- 2188842 TI - Left ventricular dysfunction and progression to clinical congestive heart failure: the case for earlier intervention. AB - Progressive left ventricular dilatation and dysfunction can occur following transmural myocardial infarction and ventricular volumes are primary predictors of survival. The relationship between left ventricular dysfunction and clinical congestive heart failure is variable and left ventricular dysfunction is often advanced at the time of clinical presentation. Although modern treatment can provide definite haemodynamic and symptomatic benefit for patients with congestive heart failure and improve survival, such treatment is essentially palliative in many cases; there is therefore a need to consider earlier intervention. Experimental animal studies which have shown improved ventricular performance and survival with treatment following myocardial infarction strengthen the rationale for a preventive approach. Initial clinical studies have demonstrated that treatment can improve asymptomatic ventricular dysfunction following myocardial infarction. Immediate intervention following infarction may provide even more significant benefit and the results of ongoing large-scale studies are awaited to determine the value of this approach. PMID- 2188843 TI - Heart failure--the options for therapy. AB - Diuretics and angiotensin-converting enzyme inhibitors currently are the mainstay of both acute and chronic heart failure management. They have earned their place by bringing measurable and reliable clinical benefit to patients with all grades and types of heart failure. Other treatments--digoxin, vasodilators and inotropes -offer less secure efficacy and their clinical role is at times controversial. The need for new remedies is inescapable. Despite current therapy, heart failure causes a distressing reduction in both quality and quantity of life. As knowledge of the pathophysiology of heart failure is gained, more selective treatment options may become available offering hitherto unknown specificity but demanding remarkable levels of diagnostic accuracy. PMID- 2188844 TI - Abnormal intracellular calcium handling in acute and chronic heart failure: role in systolic and diastolic dysfunction. AB - Acute or chronic heart failure may be caused by one or more of a variety of abnormalities including changes in excitation-contraction coupling processes (i.e. decreased availability of activator Ca2+ or a change in myofilament Ca2+ responsiveness), a change in myocardial energetics, or a change in extracellular factors, such as connective tissue content. Most of the animal and human models of acute cardiac failure that we have studied in our laboratory (i.e. negative inotropic responses to drugs, hypoxia, acidosis and ischaemia) appear to involve changes in excitation-contraction coupling as the predominant cause of dysfunction. On the other hand, the models of chronic cardiac dysfunction that we have studied (i.e. chronic right ventricular pressure overload in ferrets, hypertrophic cardiomyopathy in Syrian hamsters, hypertensive cardiomyopathy in rats, hypothyroidism in ferrets, end-stage dilated and hypertrophic cardiomyopathy in man) predominantly appear to reflect a combination of changes involving abnormalities in both excitation-contraction coupling and extracellular factors involving myocyte drop-out and increases in connective tissue content. However. In most of these models of acute and chronic heart failure, abnormal intracellular Ca2+ handling appears to be a major cause of both systolic and diastolic dysfunction. PMID- 2188845 TI - A comparison of the haemodynamic and hormonal effects of low and conventional dose cyclopenthiazide in normal volunteers. AB - In this study we compared low (125 micrograms) and conventional (500 micrograms) doses of cyclopenthiazide on the renin angiotensin system, plasma and extracellular fluid volumes and the pressor responsiveness to angiotensin II since we have previously shown that the two doses have the same antihypertensive effect but different effects on plasma renin activity. Following a two week placebo run-in period, 8 healthy male volunteers received 125 micrograms or 500 micrograms of cyclopenthiazide for 2 treatment periods of 4 weeks as part of a double blind, 2-part crossover study with treatment periods separated by a 4-week placebo washout phase. Measurements were made on two study days at the beginning and end of the active treatment periods. On the first day serum potassium, plasma renin activity and plasma angiotensin II levels were measured after a 1 h period of supine rest. Plasma and extracellular fluid volumes were also measured after appropriate equilibration times. The blood pressure responses to angiotensin II were assessed on day 2. The 500 micrograms dose of cyclopenthiazide had a greater effect than the 125 micrograms dose on plasma renin activity, serum potassium, angiotensin II levels and extracellular fluid volumes. Neither drug had any effect on plasma volume or the responsiveness to infused angiotensin II. Low dose cyclopenthiazide failed to increase angiotensin II levels, contract body fluid volumes or attenuate vascular reactivity in normotensive volunteers. PMID- 2188846 TI - Effect of diuretics on captopril-induced urinary zinc excretion. AB - The urinary zinc/creatinine ratio has been measured in five groups of patients with essential hypertension and in a group of healthy controls. The first four groups of patients consisted of subjects being treated for at least three months with captopril alone, hydrochlorothiazide alone, captopril plus hydrochlorothiazide, or captopril and furosemide. The fifth group comprised hypertensive patients not on any medication. The first four patient groups exhibited significantly increased urinary zinc/creatinine ratios when compared to the control and untreated hypertensive groups, but in the two combination regimens there was little zincuria. It is suggested that both diuretics inactivate the zincuric effect of captopril by binding to its sulphydryl group within the tubular lumen. PMID- 2188848 TI - Blood flow in the atrophied pancreas. AB - Pancreatic and islet blood flow was measured by quantitative determination of microspheres within atrophied pancreases of rats rendered dietarily copper deficient. The deficient state effects selective acinar necrosis and its replacement with non-inflammatory lipomatosis. While blood flow to lipomatous glands remained intact, it was significantly less (0.41 +/- 0.02 ml/min X g pancreas) compared to normal control glands (0.50 +/- 0.01 ml/min X g pancreas). Blood flow to islets, which remain unaffected by selective acinar atrophy of the copper-deficient state, was not significantly altered (50.8 +/- 2.13 microliters/min X g pancreas) compared to controls (55.7 +/- 2.66 microliters/min X g pancreas). The percent of islet blood flow (IBF) within atrophied glands (12.2 +/- 0.31) was found to be significantly greater than control glands (10.7 +/- 0.21). It is suggested that the maintenance of IBF and IBF percentage in the atrophic pancreas may reflect the parallel arrangement of islet angioarchitecture which based on morphological data is not appreciably altered with attenuation of acinar plexuses. Microspheres, although not quantitated, were also found distributed within the adventitia of ducts as well as in vessels supplying intrapancreatic nerves and ganglia which remain intact in copper deficiency induced acinar atrophy. PMID- 2188847 TI - Insulin-induced increase in heart rate and its prevention by propranolol. AB - Acute hyperinsulinaemia in the absence of changes in blood glucose increases heart rate in man. Animal studies have suggested that beta-adrenergic blockade does not prevent the insulin-induced increase in heart rate. The aim of the present study was to investigate the acute effect of insulin on heart rate and blood pressure in non diabetic subjects and, in particular, to determine whether beta-adrenergic receptor blockade would significantly influence the effect. On separate days 9 healthy young volunteers were pretreated with either 80 mg propranolol or placebo p.o. After a 60-90 min period of heart rate and blood pressure stabilization, a placebo injection was given intravenously and heart rate and blood pressure were then monitored every 5 min. After 30 min insulin Actrapid MC 0.2 IU/kg body weight was given i.v. A 20% glucose infusion was given to maintain blood glucose at its fasting level. After insulin administration, a rapid and statistically significant increase in heart rate was observed when the patients were pretreated with placebo; pretreatment with propranolol completely prevented this effect. Serum insulin levels were significantly higher than baseline at all times and there was no significant change in blood glucose. The results are consistent with the hypothesis that the insulin-induced increase in heart rate in man may result from stimulation of cardiac sympathetic activity. PMID- 2188849 TI - Isolation in Italy of a verotoxin-producing strain of Escherichia coli O157:H7 from a child with hemolytic-uraemic syndrome. AB - Verotoxin-producing Escherichia coli O157:H7 was isolated for the first time in Italy from a child with hemolytic-uremic syndrome and his asymptomatic sister. Both parents remained asymptomatic, and neither had evidence of this infection. The source of the infection was not identified, but the children had eaten ground beef during the 15 days prior to the onset of symptoms. PMID- 2188850 TI - Intra and inter-person sources of variability in fat intake in a feeding trial of 14 men. AB - An impediment to analyzing the effect of nutritional factors on biologic processes or health status in human populations arises from the relatively small dietary differences that exist between individuals in relation to large periodic fluctuations in dietary intake and the imprecision with which diet is normally assessed. We report here on characteristics of dietary variability in a group of 14 young men who successfully completed an intervention study specifically designed to create large differences in fat intake between baseline and two dietary intervention-periods each lasting two months (during which safflower and coconut oil supplements were given). We found that in the second supplemental phase of the intervention inter-person sources of variability were greatly increased over the low-fat baseline values. For proportion of calories as fat it increased to 64.2% of total variance from 21.6% without supplementation; for saturated fatty acids, 47.3% from 17.7%; for polyunsaturated fatty acids, 62.4% from 22.8%; and for the P:S ratio, 71.5% from 21.6%. During the first intervention phase we observed only moderate changes. Reasons for the intervention phase differences in effect, implications for feeding trials designed to look at dietary fat effects, and the need for future studies aimed at clarifying these results are discussed. PMID- 2188851 TI - Demonstration of enterotoxigenic Escherichia coli in diarrheic broiler chicks. AB - An investigation was made to survey the possible presence of enterotoxigenic Escherichia coli (ETEC) in the stools of diarrheal chicks. We analyzed two outbreaks of diarrhea in broiler chicks at two independent farms in the Philippines, from which no pathogens other than Escherichia coli were found. In one outbreak at Farm #1, all 42 isolates produced heat-labile enterotoxin (LT), with 3 of these isolates also producing heat-stable enterotoxin (ST). The O serotypes of 15 strains tested randomly could not be identified as any known serotype (0-antigen; 1-170). In another outbreak at Farm #2, 7 out of 52 isolates produced only LT, their subtypes being identified as O-149 or O-8, common serotypes in pig ETEC. Strains from Farm #1 did not produce any pili usually found in human ETEC. We believe this to be the first isolation of ETEC from diarrheal chicks. PMID- 2188852 TI - Risk of AIDS in HIV seroconverters: a comparison between intravenous drug users and homosexual males. AB - A multicentre cohort study was conducted in Italy to estimate the risk of developing AIDS in 261 intravenous drug users and 89 homosexual males for whom the seroconversion period was known. Four years after HIV seroconversion, AIDS incidence, estimated by Kaplan-Meier survival technique, was 13.8% for intravenous drug users and 16.2% for homosexual males; the difference was not statistically significant. These findings suggest that four years after seroconversion the risk of developing AIDS in HIV seropositive intravenous drug users is no higher than that of subjects who acquired HIV infection through sexual contact. PMID- 2188853 TI - Antilymphocyte immunoglobulins stimulate peripheral blood lymphocytes to proliferate and release lymphokines. AB - Five different preparations of antilymphocyte immunoglobulins (ATG) and antithymocyte immunoglobulins (ALG) with good or little clinical response were compared for their hematopoietic and immunological activities. All ATG/ALG lots demonstrated complement-mediated cytotoxicity on peripheral blood mononuclear cells. They had different titers of antibody specificities against lymphocyte cell membrane antigens. Neither clinically effective nor ineffective lots demonstrated any apparent colony stimulating activity on bone marrow mononuclear cells. Purified Natural Killer cells failed to be stimulated by ATG/ALG in liquid culture. ATG/ALG demonstrated potent T-cell stimulating activity comparable to phytohemagglutinin. This stimulation was blocked by anti-IL-2 receptor monoclonal antibodies, and was inhibited dose-dependently by cyclosporin-A. Some clinically ineffective ATG/ALG lots also stimulated T cells to release lymphokines. The differences in these characteristics among ATG/ALG lots provide some clues to guide further efforts to elucidate a key mechanism of therapeutic effectiveness. PMID- 2188854 TI - Idarubicin (4-demethoxydaunorubicin) as single agent for remission induction of previously untreated acute promyelocytic leukemia: a pilot study of the Italian cooperative group GIMEMA. AB - Because of the reported high sensitivity of acute promyelocytic leukemia to daunorubicin, we treated 27 consecutive, newly diagnosed, acute promyelocytic leukemia (APL) patients with the new anthracycline idarubicin (IDA) as induction therapy. IDA dosage ranged from 0.25 to 0.30 mg/kg/day and the drug was administered as single agent during a single induction course of 6 days. A total of 22/27 patients (81%) achieved complete remission, 4 (15%) died during induction and 1 patient was resistant to IDA. Extrahematological toxicity was acceptable. A total of 13/22 patients having achieved CR are still alive and in first CR after a median follow-up of 12 months. As for the treatment of the coagulopathy present in APL: 17/27 (63%) received tranexamic acid (6 g/daily) in continuous infusion for total of 7 d. None of the patients treated with tranexamic acid experienced thromboembolic complications. In conclusion, this multicentric pilot study confirms the antileukemic potency of IDA and the high sensitivity of APL to anthracycline derivatives. PMID- 2188855 TI - Obstructive jaundice secondary to non-Hodgkin's lymphoma: usefulness of ultrasound-guided fine-needle aspiration biopsy (UG-FNAB). PMID- 2188856 TI - [Syncope of unknown origin after electrophysiologic study: is the treatment with pacemaker useful?]. AB - The usefulness of pacemaker treatment appears doubtful in patients suffering from syncope of unknown origin after a complete diagnostic evaluation, which includes electrophysiological study. To better assess the effectiveness of this therapy, 24 patients with syncope of unknown origin and negative electrophysiological study were prospectively and alternatively assigned to treatment with pacemaker (group A) vs treatment without pacemaker (group B). Group A included 12 patients (7 males, 5 females) with a mean age of 64 +/- 10 years. No heart disease was present in 7 cases (58%); 3 cases had chronic ischaemic heart disease (25%) and 2 had hypertensive heart disease (17%). The standard ECG was normal in 7 patients, while various conduction abnormalities were observed in the other 5. The mean number of syncopal episodes was 4.8 +/- 3.9 per patient, and the mean between the onset of symptoms and the beginning of this study was 32 +/- 42 months. In these 12 cases a VVI-M pacemaker was implanted, at a programmed rate of 50 or 60 bpm; in three subjects, the pacemaker was of the diagnostic type ("bradycardia event counter"). Group B included 12 patients (8 females, 4 males) with a mean age of 56 +/- 11 years. Organic heart disease was absent in 7 cases (58%); 4 patients showed hypertensive heart disease (33%) and 1 had mitral prolapse (9%). The ECG was normal in 9 subjects. The mean number of syncopes was 3.2 +/- 1.5 per patient; the mean interval since the onset of symptoms was 18 +/- 19 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188857 TI - [The problem of ventricular situs]. PMID- 2188858 TI - Segmental situs in congenital heart disease: a fundamental concept. PMID- 2188859 TI - [Renin-angiotensin system and heart function]. PMID- 2188860 TI - [The converting enzyme inhibitors in myocardial infarct in acute phase. Experimental data and prospects]. PMID- 2188861 TI - [Biological manifestations of a prethrombotic state in developmental Crohn's disease]. AB - The authors have studied 21 patients with Crohn's disease and have looked for signs of platelet and blood coagulation activation, by measuring platelet factor 4, beta thromboglobulin and fibrinopeptide A: a fibrinolytic system study with tissue plasminogen activator assessment has also been made. Beta thromboglobulin, platelet factor 4 and fibrinopeptide A were increased in 80 per cent, 100 per cent and 60 per cent of cases respectively. Beta thromboglobulin was significantly correlated with the Van Hees activity index. Plasminogen before venous stasis was significantly decreased and 9 patients had a plasminogen release defect. The relationship between Crohn's disease and thrombosis might partially be explained by a release of inflammation mediators and/or endotoxins: these mediators might induce thrombosis by interfering with the antithrombogenic properties of the endothelial cell. In conclusion these data prove that active Crohn's disease is currently associated with a prethrombotic state, present biologic tests that might predict a venous or arterial thrombosis at short term are not available. PMID- 2188862 TI - [Intra-epithelial cancer of the anal canal. Pathogenic study apropos of 5 cases]. AB - Anal carcinomas are rare and their precancerous conditions are not well known. Two populations at risk are described, elderly women and, recently, homosexual males. Early detection of dysplastic lesions or intraepithelial carcinoma in the anal mucosa could lead to preservation on the anal sphincter and consequently to improvement of quality of survival. The present study included 3 women and 2 men. The pathological examination of the surgical specimens in these 5 cases (hemorrhoidal procidence, rectal prolapsus, fibrous polyps, fissure) showed, in all cases, an intraepithelial carcinoma developed in the squamous epithelium of the anal canal. In one of the 5 cases, the anal lesion was concomitant with an intraepithelial carcinoma of the uterine cervix. Complete local resection of the lesions were performed in all cases, associated with complementary radiotherapy in one patient. On follow-up, we observed one recurrence after 8 months in one out of 5 patients. All patients are alive. Histogically, the specimens showed an intraepithelial carcinoma in all 5 cases, with a microinvasive carcinoma in one case. The transitional mucosa of the anal canal showed dysplatic modification in all cases. Immunohistochemical study of the 5 cases did not discern the papilloma virus antigene. In the one case where it was performed, molecular hybridization showed a type 33 papillomavirus. The risk factors of anal carcinomas seems to be changing, in particularly the incidence is increasing in the homosexual patients. In this particular population, as in the uterine cervix, the human papilloma virus is probably one of the main etiological factors. The management of these lesions is not well-defined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188863 TI - [Azathioprine, 6-mercaptopurine, and inflammatory diseases of the intestine]. PMID- 2188864 TI - [Clinical implications of interactions between hepatitis B virus and mononuclear leukocytes]. PMID- 2188865 TI - [Arterial thrombotic complications in Crohn's disease]. AB - In a series of 230 observations of Crohn's disease, the authors describe 4 cases of arterial thrombosis; two of them involving cerebral arteries. These complications occurred in young women without any notable risk factor for atheroma. All patients had highly active Crohn's disease when arterial thrombosis occurred: two of them had several episodes of thrombosis and three, extraintestinal manifestations. As the arterial thromboses are often severe, rarely foreseeable and the venous thromboses frequent, the point is whether to use anticoagulants. When Crohn's disease is highly active, but only if there are no hemorrhagic lesions, anticoagulants at prophylactic doses may be recommended. How to define more exactly a high risk thromboses population deserves further investigation. PMID- 2188866 TI - [Adenomyoma of the distal common bile duct. An uncommon cause of stenosis of the extrahepatic bile duct]. AB - We report the case of a 68-year-old man with adenomyoma of the distal common bile duct, fortuitously discovered on a surgical specimen of a Whipple procedure. To our knowledge, three similar cases have been reported; all patients were operated on with the diagnosis of malignancy: adenomyoma was always discovered on the surgical specimen. Adenomyomas are rare tumors and their origin is discussed. Adenomyoma of the distal common hile duct should be considered as enteropancreatic heterotopia. PMID- 2188867 TI - [Dissecting duodenal hematoma: severe complication of endoscopic hemostasis of hemorrhagic duodenal ulcer]. PMID- 2188868 TI - Escherichia coli O157:H7-associated colitis. A clinical and histological study of 11 cases. AB - Hemorrhagic colitis is characterized by abdominal cramps, bloody diarrhea, and no or low-grade fever. Most cases are caused by the Shiga-like toxin-producing bacteria, Escherichia coli O157:H7. Nineteen colonic biopsy specimens and one resection specimen were reviewed from 11 patients with E. coli O157:H7-associated colitis to determine whether histologic features could be useful in diagnosis or in suggesting pathogenesis. All specimens showed hemorrhage and edema in the lamina propria. Specimens from nine patients were focally necrotic and showed hemorrhage and acute inflammation in the superficial mucosa with preservation of the deep crypts, similar to the pattern of injury associated with acute ischemic colitis. Specimens from five patients showed neutrophils focally infiltrating the lamina propria and crypts, resembling the pattern of injury seen in infectious colitis. One or both of these histologic patterns were observed in specimens from all but one patient. Specimens from four patients had poorly formed inflammatory pseudomembranes. It is concluded that the histologic features of E. coli O157:H7 associated colitis resemble a combination of ischemic and infectious injuries similar to those described in toxin-mediated Clostridium difficile-associated colitis. This suggests that the toxin(s) produced by these E. coliplay a role in the colonic injury. Infection with E. coli O157:H7 should be considered in the differential diagnosis of ischemic and infectious colitis. PMID- 2188869 TI - Antinuclear antibodies directed to a 200-kilodalton polypeptide of the nuclear envelope in primary biliary cirrhosis. A clinical and immunological study of a series of 150 patients with primary biliary cirrhosis. AB - Antinuclear antibodies giving a perinuclear fluorescence and directed to a 200 kilodalton polypeptide of the nuclear envelope have been described in primary biliary cirrhosis. The purpose of this study, based on a series of 150 patients with primary biliary cirrhosis, was to ascertain the prevalence of these antibodies and to compare patients with and without these antibodies. Antinuclear antibodies giving a perinuclear fluorescence were demonstrated in 43 of the 150 patients (29%); antibodies directed to the 200-kilodalton polypeptide of the nuclear envelope were found in 40 of these 43 patients. Asthenia, arthralgia, associated extrahepatic diseases, Raynaud's phenomenon, and other antinuclear specificities were significantly less common, and titers of antimitochondrial antibodies were significantly lower in patients with antibodies directed to the 200-kilodalton polypeptide of the nuclear envelope than in patients without these antibodies. Clinical outcome, liver tests, and histological lesions did not significantly differ in patients with and without these antibodies. PMID- 2188870 TI - Antibodies against mitochondrial dehydrogenase complexes in primary biliary cirrhosis. AB - Antimitochondrial antibodies, serological hallmarks of primary biliary cirrhosis, recently were found to be directed against the E2 subunits of mitochondrial dehydrogenase complexes (pyruvate, branched-chain ketoacid, and alpha ketoglutarate dehydrogenases). The objectives of this study were to extend these findings and to determine whether purified immunoglobulin from the sera of patients with primary biliary cirrhosis inhibit activity of these dehydrogenase complexes in vitro. Sera were examined from 14 patients with primary biliary cirrhosis (13 mitochondrial antibody positive), 23 with rheumatic diseases and 30 with chronic active hepatitis (all 53 positive for mitochondrial antibodies by indirect immunofluorescence), 10 with alcoholic liver disease, and 5 normal controls. Antibodies against pyruvate dehydrogenase, branched-chain alpha ketoacid dehydrogenase and alpha-ketoglutarate dehydrogenase complexes were detected by immunoblot and quantified by enzyme-linked immunosorbent assay. Of the 14 serum samples obtained from patients with primary biliary cirrhosis, 13, 11, and 2 samples tested positive by immunoblot for the E2 subunits of pyruvate, branched-chain ketoacid, and alpha-ketoglutarate dehydrogenase, respectively. In contrast, samples from subjects with rheumatic diseases, chronic active hepatitis, and alcoholic liver disease and control subjects tested negative for these antibodies. Serum immunoglobulin G with high titers of mitochondrial antibodies showed concentration-dependent inhibition of activity of the dehydrogenase complexes, and close correlation (r = 0.917, n = 13) was observed between inhibitory activity against pyruvate dehydrogenase complex and the reciprocal titer of immunoglobulin against this complex. These data suggest that such autoantibodies, besides serving as diagnostic markers for primary biliary cirrhosis, may have a pathogenic role by their ability to inhibit important mitochondrial enzymes. PMID- 2188871 TI - Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo-controlled study. AB - Parenteral S-adenosylmethionine proved to be effective in reversing intrahepatic cholestasis in pregnant women. Based on these findings, a prospective multicenter, double-blind, placebo-controlled trial was planned to assess whether oral S-adenosylmethionine is effective in cholestatic patients with chronic liver disease. Accordingly, 220 inpatients (26% chronic active hepatitis, 68% cirrhosis, 6% primary biliary cirrhosis) with stable (1 month or more) at least twofold increases in serum total and conjugated bilirubin and alkaline phosphatase volunteered for the trial. Serum markers of cholestasis significantly (P less than 0.01) decreased after oral S-adenosylmethionine administration (1600 mg/day), and their values were significantly (P less than 0.01) lower than the corresponding values in the placebo group. S-adenosylmethionine significantly (P less than 0.01) improved subjective symptoms such as pruritus, fatigue, and feeling of being unwell, whereas placebo was ineffective. Two patients in the S adenosylmethionine group and 9 controls (P less than 0.05) withdrew from the trial for reduced compliance because of inefficacy of treatment. Oral S adenosylmethionine was tolerated to the same extent as placebo. In conclusion, short-term administration of oral S-adenosylmethionine is more effective than placebo in improving clinical and laboratory measures of intrahepatic cholestasis and offers a new therapeutic modality for the symptomatic management of this syndrome. PMID- 2188872 TI - Nuclear DNA distribution pattern of the parenchymal cells in adenocarcinomas of the pancreas and in chronic pancreatitis. A study of archival specimens using both image and flow cytometry. AB - The nuclear DNA distribution pattern of the neoplastic parenchymal cells of 100 conventionally formalin-fixed and paraffin-embedded specimens from pancreatic adenocarcinomas and from 8 specimens of chronic pancreatitis was assessed by means of image cytometry. All material originated from pancreatic restrictions. Evaluable DNA histograms could be obtained for 77 carcinomas, and clinical data were available for 71 of these. In these 71 specimens, the nuclear DNA ploidy pattern was also investigated by means of flow cytometry. In 76 of the 77 cases, the image-cytometric DNA ploidy pattern obtained showed a "nondiploid" distribution with modal values as high as 8.5 c. In 21 cases, the neoplastic cells showed modal values in the "triploid" region. The analogous 71 flow cytometric DNA histograms could only be evaluated in 50 cases because of excessively high amounts of background and/or excessively broad peaks. In 47 cases, the nuclear DNA histogram was nondiploid according to both techniques. The patients with carcinomas whose cell nuclei showed a triploid DNA distribution showed a significantly shorter survival time than those with tumor cell populations of nontriploid DNA distribution patterns. In the 8 specimens of chronic pancreatitis, the parenchymal cells were all equipped with nuclei showing diploid DNA distribution patterns. PMID- 2188873 TI - Posttranslational processing of ras proteins. PMID- 2188875 TI - [The effect of mutation him1 characterized by enhanced induced mutagenesis on the genetic effects of 6-N-hydroxylaminopurine in Saccharomyces cerevisiae]. AB - The him1 mutation has been shown to influence the genetic effects of the mutagenic purine base analog 6-hydroxylaminopurine, i. e. inactivation of haploid cells, mutation induction, and inhibition of DNA synthesis in vivo. The influence observed is well consistent with the idea that the him1 mutation affects mismatch correction. We present evidence that during in vivo DNA replication 6 hydroxylaminopurine incorporates into the yeast DNA. PMID- 2188874 TI - Health status in inflammatory bowel disease. Biological and behavioral considerations. AB - The existing clinical measures of disease activity for inflammatory bowel disease are insufficient to explain a patient's illness experience or health outcomes. Although many disease activity measures have been devised, they are not widely accepted by clinicians because existing ones are no better than a carefully obtained clinical assessment. Furthermore, health status is determined not only by disease activity, but also by the psychological state, cultural influences, degree of social support, and effects of complications, previous surgery, and medication. To develop more accurate appraisals of the impact and severity of IBD, we must prospectively evaluate the biological and psychosocial measures that predict clinically relevant outcomes. We should then be able to develop statistically weighted scales related to specific outcome variables. Such knowledge will help us to develop more sensitive measures of illness, particularly in patients with mild disease for whom present indices are insensitive. This type of assessment should also aid in the understanding of health care utilization, medical vs. surgical options, resource allocation, and the efficacy of therapeutic trials. PMID- 2188876 TI - [Comparative analysis of the structure and function of recA genes from Serratia marcescens Sb and Escherichia coli K-12]. AB - Nucleotide sequence of the 1276 bp fragment of Serratia marcescens DNA coding for the recASM gene has been determined. This structure was shown to contain an ORF corresponding to a protein with molecular weight of 37766 D. Comparative analysis of the regulatory part of recASM and recAEC (Escherichia coli) demonstrated identity of "-35" and "-10" boxes for these genes and similarity of the SOS box and the enhancer sequences. A comparison of the amino acids sequences of RecASM, RecAEC and RecAPA (Pseudomonas aeruginosa) proteins revealed a great conservatism in the N-terminus and in some structural patches (alpha-helices and beta-sheets) of the RecA proteins predicted by the model of Blanar et al. In contrast, a strong variability of the C-terminus (for the last 25 amino acids, in particular) was revealed. A necessity for definite amino acids composition of the carboxy terminal end is discussed. PMID- 2188877 TI - [Transmission of amber mutants in phage T4. V. Positive effect of heat shock proteins on the replication of amber mutants in gene 31]. AB - The effect of growth of Escherichia coli BE, prior to infection, on multiplication of double amber mutant amN54-amNG71 in gene 31, mutant amN131 amNG114 in gene 26 and T4D wild-type at different temperatures has been studied. In the case of gene 31 mutant the increase in phage burst size, along with increase in growth temperature, was only observed. And this dependence seems to have the same character as the known dependence of growth temperature on cellular levels of heat shock proteins. Possibly, the product of gene 31 might be substituted to some extent by some heat shock protein. An antiserum against gene 31 protein immunoprecipitates heat shock protein, the molecular weight of which is close to the molecular weight of gene 31 protein. So, it seems likely that, in addition to supposed ability of this heat shock protein for functional substitution of gene 31 protein, these proteins might have some structural homology as well. PMID- 2188878 TI - Development of an immunological staging system to prognosticate disease course in malignant cervical neoplasia. AB - A multiparameter analysis of immune function was done on patients with squamous cell carcinoma of the uterine cervix to look for any variable(s) that could be correlated with the clinical stage of the disease. Five immunological variables, viz., CD4+ lymphocytes, CD4/CD8 ratio, natural killer cells, concanavalin A induced suppressor index, and circulating immune complexes, were found to consistently vary with tumor load. When these variables were subjected to a multiple regression and multivariate analysis, an equation for a diagnostic index curve was derived. Application of this equation led to an immunological staging system which could be used as an excellent prognostic indicator. The immunological staging system showed that patients classified into a particular clinical (FIGO) stage behaved in a heterogeneous way immunologically and that patients developing recurrent disease could easily be identified from those remaining disease free, even before treatment. Subsequent follow-up of these patients further confirmed this observation, with the recurrent disease group easily identifiable. These results point out the immense potential of such a staging system and the importance of immunological evaluation in the preliminary management of patients with malignant cervical neoplasia. PMID- 2188879 TI - Tumors in the lower pelvis as imaged by vaginal sonography. AB - Ultrasound is a sensitive tool for the diagnosis of cystic tumors in the lower pelvis of women. Most knowledge about the ultrasound image of such tumors is based on abdominal scanning. The value of vaginal sonography for evaluation of such tumors has, to the best of our knowledge, so far not been studied. This study was aimed at relating the vaginal sonographic image of tumors in the lower pelvis with the results of macro- and microscopic examination of the tumor. Special interest was paid to establishing ultrasound criteria for classifying unilocular tumors as benign or malignant. One hundred and eighty women who were operated on for pelvic tumors were included in the study. All women were evaluated by vaginal sonography the day before surgery. Ninety-four women were postmenopausal and eighty-six were still menstruating. Vaginal ultrasound characterized the tumor correctly as related to macroscopic examination in 96% (172/180). The sensitivity of vaginal sonography in identifying benign and malignant tumors was 82%, and the specificity, 92%. None of the unilocular tumors was malignant. Papillary formations on the inside of the cyst wall indicated an increased chance of the tumor's being malignant. There was a clear correlation between size of tumor and malignancy except for unilocular tumors. Vaginal sonography was shown to be accurate in characterizing cystic tumors in the lower pelvis. The present results also indicate that the probability that unilocular tumors less than 10 cm in diameter and without papillary formations, are malignant is low, irrespective of the woman's age. PMID- 2188880 TI - Correlation of abdominal ultrasound and computed tomography scans with second- or third-look laparotomy in patients with ovarian carcinoma. AB - To determine the best noninvasive means of evaluating response in patients with advanced ovarian carcinoma, 50 abdominal ultrasound (US) and computed tomography (CT) scans were performed in clinically disease-free ovarian cancer patients. The scans were correlated with the results obtained at a subsequent second- or third look laparotomy. CT and US were not complementary, and only metastases larger than 2 cm were detected. The overall positive predictive value of nonconcordant scans was 57% compared with 100% for concordant CT and US (95% confidence limits: 18.4-90.1 and 29.2-100%, respectively). The corresponding negative predictive values were 45 and 47% (30.2-59.9 and 30.4-61.2%, respectively), if undetected microscopic disease was classified as a false-negative result. The negative predictive value of US and CT increased only to 60% in both cases, if undetected microscopic disease was registered as a true-negative result. Compared with the pelvic examination CT and US added positive information for 4 of 22 (18%) patients with macroscopic residual disease. In this study neither CT nor US was sensitive enough to preclude second-look laparotomy. PMID- 2188881 TI - Angiomyolipoma of the vagina. AB - An angiomyolipoma arising in the vaginal apex and presenting as a pelvic mass is reported and compared with other reported cases of extrarenal angiomyolipoma. This case appears to be the second case of angiomyolipoma arising in the vaginal wall. PMID- 2188882 TI - [Immunological abnormalities in autoimmune liver diseases]. PMID- 2188883 TI - [Cordocentesis]. PMID- 2188884 TI - [Positron emission tomography in schizophrenia]. PMID- 2188886 TI - [Psoriasis: pathogenesis and therapeutic aspects]. PMID- 2188885 TI - [Anti-idiotypes against human monoclonal antibodies which recognize breast cancer associated antigens]. PMID- 2188887 TI - [Urolithiasis: B. Pharmacological and instrumental treatment of stones]. PMID- 2188888 TI - [Electrocardiographic findings in patients with mitral valve prolapse]. PMID- 2188889 TI - [Systemic lupus erythematosus and pregnancy]. PMID- 2188890 TI - The carcinogenic potential of ethyl carbamate (urethane): risk assessment at human dietary exposure levels. AB - Ethyl carbamate is found in fermented foods: bread contains 3-15 ng/g, stone fruit brandies 200-20,000 ng/g, and about one-third of table-wine samples analysed contained more than 10 ng/g. In animals, ethyl carbamate is degraded to CO2, H2O and NH3, with intermediate formation of ethanol. This degradation has been shown to be inhibited (postponed) in the mouse by ethanol concentrations in the blood of about 0.15% and higher. A quantitatively minor pathway involves a two-step oxidation of the ethyl group to vinyl carbamate and epoxyethyl carbamate, the postulated electrophilic moiety that reacts with DNA. This reaction is probably the mode of the mutagenic action observed in many cellular and animal systems. The fact that only vinyl carbamate, but not ethyl carbamate, is mutagenic in a standard Ames test is probably because there is insufficient production of the intermediate oxidation product in the standard test. Consistent with this metabolism is the carcinogenic activity of ethyl carbamate in various animal species and in different organs; this activity can be seen even after a single high dose in early life. Quantitative analysis of the total tumour incidences after chronic exposure of rats and mice to 0.1-12.5 mg ethyl carbamate/kg body weight/day in the drinking-water showed a dose-related increase. The main target organs were the mammary gland (female rats and mice having similar susceptibilities) and the lung (mice only). On the basis of sex- and organ-specific tumour data and with a linear extrapolation to a negligible increase of the lifetime tumour incidence by 0.0001% (one additional tumour in one million individuals exposed for life), a "virtually safe dose" of 20 to 80 ng/kg body weight/day was estimated. The daily burden reached under normal dietary habits without alcoholic beverages is in the range of about 20 ng/kg body weight/day. Regular table-wine consumption would increase the risk by a factor of up to five. Regular drinking of 20 to 40 ml stone-fruit brandy per day could raise the calculated lifetime tumour risk to near 0.01%. PMID- 2188891 TI - [The implantable automatic cardioverter-defibrillator]. AB - In addition to medical treatment for ventricular tachyarrhythmias which has not proven to be sufficient, nonmedical modes of treatment are available such as electrophysiologically-guided surgical measures and catheter ablation, both of which are restricted to only a relatively small patient population and require further technical refinement. In 1980, Mirowski introduced the automatic implantable defibrillator and, to date, world-wide, this device has been implanted in 8000 patients. CHARACTERISTICS AND IMPLANTATION OF THE AUTOMATIC IMPLANTABLE CARDIOVERTER/DEFIBRILLATOR (AICD): The AICD continuously monitors the electrical activity of the heart, recognizes the onset of threatening ventricular tachycardias and terminates these according to the respectively programmed mode by delivering direct current shocks or stimuli. The currently used defibrillators consist of an impulse generator with lithium batteries and an electrode system. The batteries can charge a capacitor with about 700 volts in five to eight seconds which produces a current with an energy up to 30 Joules on discharge. The current is delivered either by two plate electrodes on the right and left ventricles or a plate electrode on the left ventricle and a spiral electrode inserted in the superior vena cava. The electrodes also serve the purpose of tachycardia detection by means of an electrical signal, the probability density function (PDF), that is, a significant decrease in the potentials to isoelectric. With this, it is only possible to terminate ventricular fibrillation. Additional electrical detection criteria are obtained and analyzed by two adjacently positioned epicardial screw electrodes or a bipolar endocardial electrode, enable identification of ventricular tachycardia as well. If the tachycardia detection criteria are fulfilled, the capacitor is discharged according to its programmed shock energy. In 1988, programmable defibrillators were introduced. Current defibrillator treatment also incorporates the possibility for antitachycardia stimulation. Attempts to use, instead of the monophase, square-wave impulse, a biphasic defibrillation impulse, to achieve a sequential impulse and to make use of the bidirectional impulse extension have rendered improved reliability for tachycardia termination and energy savings. After median sternotomy, the plate electrodes are usually sutured to the epicardium and the spiral electrode for the bipolar ECG is positioned at the anterior aspect of the right ventricle. The generator is implanted on the left side para-umbilically in subcutaneous or subfascial tissue. With the subxyphoid approach to avoid sternotomy, the plate electrode is sutured extrapericardially over the left ventricle and the spiral electrode is positioned at the epicardium. Alternatively, for those in whom prior cardiac surgery has been carried out, a lateral thoracotomy can be used. The defibrillation threshold, that is the lowest possible energy for defibrillation of ventricular fibrillation or ventricular tachycardia, should be determined intraoperatively after stimulation of the arrhythmia. The energy required for termination of a stable ventricular tachycardia is usually less than that for termination of ventricular fibrillation and can be determined postoperatively. A margin of security should be taken into consideration which, for defibrillation thresholds of up to 10 Joules, is about twice the amount of the defibrillation threshold itself.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2188892 TI - [Anti-tachycardia surgery in ventricular arrhythmia]. AB - Recurrent sustained ventricular tachycardia (VT) is associated predominantly with ischemic heart disease, mostly in the chronic phase after myocardial infarction. Potentially life-threatening and drug-refractory ventricular tachycardias are called malignant VT. In the Federal Republic of Germany, VT develops in about 3,000 to 5,000 patients per year from the 100,000 who survive a myocardial infarction. About 10% of these patients prove to be medically-refractory or additionally are considered candidates for aneurysmectomy or coronary revascularization. Overall, for the Federal Republic of Germany, there is a need for approximately 500 to 1000 antitachycardia operations each year. The morphologic substrate for malignant VT are ischemically-damaged inhomogeneously structured arrhythmogenic areas. The morphology results in electrical inhomogeneity which predisposes to electrophysiologic reentry phenomena. NATURAL HISTORY: The survival rate of patients with malignant VT who are not surgically treated is 70% at one year and 20 to 40% at four years (Figure 1). In those in whom the tachycardia can be medically controlled, the prognosis is 10.5 times more favorable than in those with medically-refractory arrhythmias. In one study of 45 patients with recurrent, sustained VT, only 20% of those with medical refractoriness were free of renewed arrhythmic events after 30 weeks as compared to 90% whose treatment had been designated effective (p less than 0.0004) (Figure 2). According to a further study, for patients with drug-refractory VT, the probability for sudden death within four years was 55% as compared with 5% for those with medically-controlled VT (p less than 0.0002). SURGICAL TREATMENT: The concept of surgical treatment of malignant VT encompasses delineation of the arrhythmogenic area by means of endocardial mapping and surgical ablation. Arrhythmogenic areas are located mostly in the transition zone between the viable muscle and an aneurysm at the left ventricular endomyocardial septum. With mapping, by means of local measurements of activity times, impulse spread throughout the heart can be recorded in a cartographic system. The left ventricular endocardial activation should be determined during sinus rhythm and tachycardia and, with normothermic extracorporeal circulation the left ventricle is incised, mostly in the aneurysmatic antero-apical area, prior to sequential interrogation of the endocardial surface (Figure 3). As an alternative to point for-point mapping, by means of multi-terminal electrodes, electrocardiograms can be obtained simultaneously from multiple positions. During tachycardia, the earliest activation can be found in the arrhythmogenic area (Figure 4); during sinus rhythm, in these areas, delayed, low-amplitude and fragmented signals are present (Figure 5). Macroscopically, endomyocardial fibrosis is a common finding. The arrhythmogenic morphologic substrate is either reduced or rendered a homogeneous scar without electrical activity. In this regard, techniques for endomyocardial resection have been described by Harken and Josephson. As an alternative procedure. Guiraudon introduced the encircling endomyocardial resection with which the pathologic reentry circuit can be blocked and the microvascular blood flow to arrhythmogenic areas eliminated. One modification, the partial encircling resection, appears to yield comparable effectiveness with less damage to left ventricular function (Figure 6).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2188893 TI - [New aspects of the electrophysiologic effect of antiarrhythmic agents]. AB - BASIC ACTIONS: According to Vaughan Williams antiarrhythmic agents are divided into four classes of action (Table 1). A given agent may display actions of several classes. In general, except for class II drugs there is no causal relationship between the class of action and the mechanism precipitating the arrhythmia. MECHANISM OF ACTION OF CLASS I DRUGS: The effect of class I antiarrhythmic drugs is primarily based on prolongation of the refractory period. It is assumed that the sodium channel can be in one of at least three functional conditions (Figure 1), resting, activated or inactivated. Conductance is achieved only in the state of activation, during the initial phase of the action potential which is caused by rapid sodium influx. The transition from inactivation to resting condition, which is prerequisite for renewed activation, takes place during repolarization and is responsible for the refractory period of the action potential (Figure 1). Class I antiarrhythmic drugs block the sodium channels such that they remain in a nonconductive state. As a function of the number of inoperative sodium channels, sodium influx is reduced and the rate of rise of the action potential is diminished. In order to enable sufficient sodium channels to make the transition from inactivated to resting condition, repolarization of the action potential has to continue and, concomitantly, the absolute refractory period is increased. Since the attenuation of the rapid sodium influx also causes a decrease in the conduction velocity in myocardium and in the intraventricular conduction system, reentry arrhythmias can be precipitated. DIFFERENCES IN THE ACTION OF CLASS I DRUGS: Due to different rate-dependency of the various class I drugs and the effect on the duration of the action potential as well as on specified ECG parameters, subclasses a, b and c were designated (Table 2). Access of the drug to the sodium channel receptor is facilitated during activation and inactivation but not in the resting condition. Accordingly, the effect increases in proportion to the frequency with which the sodium channel is opened. With the beginning of the cardiac cycle, there is an exponential increase in the number of blocked sodium channels and, with transition to the resting condition, an exponential decrease (Figure 2). The velocity of the increase or decrease is dependent on the properties of the given agent. Substance with rapid binding kinetics, that is time constants of 0.2 to 2.0 s are assigned to group Ib, those with time constants of 8 to 14 s to group Ic (Table 3). Group Ia is intermediate. A similar grouping is yielded on assignment according to the temporal course of deblocking. EXPLANATION FOR THE DIFFERENCES IN EFFECTS: With antiarrhythmic agents of class Ib, due to their rapid binding kinetics, at a rate of approximately 1 Hz (60/min) steady-state is achieved with no accumulation of block. Each incoming impulse with a normal interval can activate the unblocked membrane (Figure 2). Premature impulses occurring with shorter intervals are inhibited more the earlier their incidence. Consequently, class Ib antiarrhythmic drugs are particularly effective for premature beats and frequent tachycardias while, during normal sinus rhythm, in some instances, no effect such as PQ or QRS prolongation can be observed (Table 2).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2188894 TI - New aspects of the clinical use of anti-arrhythmia agents with special reference to acute therapy of ventricular tachycardia (lidocaine vs. ajmaline). AB - Antiarrhythmic treatment is based on the hypothesis that ventricular premature beats (VPBs), in the presence of underlying cardiac disease and impaired ventricular function, may predispose to sudden cardiac death. The effectiveness of treatment, however, has not been proven. For acute treatment of paroxysmal ventricular tachycardia, on comparison of the effectiveness of lidocaine and ajmaline, some new aspects have been rendered. VENTRICULAR PREMATURE BEATS (VPB): Isolated VPBs can be found in 40 to 75% of healthy subjects; if their number is substantial, investigation is warranted. For VPBs with subjective symptoms, beta receptor blockers or specific antiarrhythmic agents, if necessary in combination, may be given. In several studies it has been shown that the prognosis of patients with frequent and complex VPBs, that is couplets and salvos, without heart disease is not compromised. In one long-term study over an average of 6.5 years, sudden death was observed in only one of 70 subjects who had 566 VPBs/24 hours, 60% additionally couplets and 26% salvos in the Holter ECG. Accordingly, treatment for the sake of prognosis is not warranted. For patients with mitral valve prolapse or only mildly impaired ventricular function and asymptomatic arrhythmias, treatment is not necessary since it has not been shown to be beneficial. Coronary artery disease is the most frequent cause of ventricular arrhythmias and sudden death. In numerous studies in patients after myocardial infarction, a relationship has been recognized between frequent and complex VPBs and overall mortality as well as sudden death. Particularly at risk are patients with very frequent and complex VPBs with additional impairment of ejection fraction to less than 30 to 40% but this group only accounts for 10% of patients after infarction. Only in one interventional study, carried out with aprindine, there was a significant reduction in overall mortality from 12.5 to 7.8% with an adverse reaction rate, however, of 21%. In high-risk patients with a low ejection fraction and numerous, complex VPBs as well, in a further study with aprindine, after one year, there was no decrease in overall mortality as compared with the placebo group. The cause for the insufficient effectiveness of the antiarrhythmic agents in various interventional studies has been attributed to a limited number of patients, rigid dosing regimens, inadequate suppression of VPBs and a high incidence of adverse reactions. In the multicenter, randomized, placebo controlled CAST study with newer substances, a total of 2309 patients with essentially asymptomatic VPBs at a rate of more than 6/hour and an ejection fraction less than 55% or 40% admitted more than 90 days after infarction, respectively, were followed from six days to two years after myocardial infarction to determine if the significant suppression of VPBs in patients with coronary artery disease with antiarrhythmic agents leads to a reduction in arrhythmia-associated deaths. Flecainide, encainide and moricizine led to a significant suppression of VPBs in 75% of the patients. After an average of ten months, the rate of arrhythmia-induced deaths of 4.5% in those treated with encainide or flecainide was significantly higher than the 1.2% observed in the placebo group. These results appear attributable to a proarrhythmic effect of the class IC drugs during long-term treatment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2188895 TI - [Can sudden cardiac death be prevented by treatment with anti-arrhythmia drugs?]. AB - Sudden cardiac death is defined as death due to a primary cardiac cause or mechanism, occurring within one hour of the onset of acute illness in a person thought to be free of, or with symptomatically mild, heart disease, or simply prehospital death. Of persons dying suddenly, 90% have coronary artery disease, less commonly, dilated cardiomyopathy or hypertrophic cardiomyopathy, preexcitation syndrome, long QT-syndrome, conduction disturbances, congenital or valvular heart disease as well as cardiac tamponade are responsible. In the USA, the incidence of sudden cardiac death is approximately 450,000 per year, in the Federal Republic of Germany the number lies at about 70,000 to 80,000. The most important risk factors for sudden cardiac death are impaired left ventricular ejection fraction, myocardial ischemia and arrhythmias. In general, sudden cardiac death is caused by ventricular fibrillation which arises mainly by degeneration of ventricular tachycardia (VT). The terminal arrhythmia, it is assumed, is precipitated by premature ventricular beats originating in an arrhythmogenic substrate. MEDICAL ANTIARRHYTHMIC TREATMENT IN PATIENTS WITH CORONARY ARTERY DISEASE AFTER MYOCARDIAL INFARCTION: STUDIES WITH CLASS I DRUGS: The results of nine large, randomized , controlled studies are available in which the mortality of patients on antiarrhythmic treatment has been studied (Table 1). Two studies each were carried out with aprindine, phenytoin, mexiletine and tocainide as well as one study with endainide, flecainide or morizicine. With the exception of the CAST study, no study showed a significant difference between treated patients and the control group with respect to mortality or incidence of sudden cardiac death. The CAST study was terminated after ten months because the administration of flecainide and encainide led to overall mortality of 7.7% vs. 3.0% in the control group and the rate of sudden cardiac death at 4.5% was significantly higher in the treatment group than the 1.2% incidence found in controls (Table 2). For nearly all of the studies described, the patient groups were not sufficiently large and subgrouping according to patient characteristics was not carried out such that possibly, inhomogeneity of the entire collective may not have been recognized precluding identification of some individuals who may have shown benefit from antiarrhythmic treatment. The necessity for treatment in many of those receiving drugs is questionable since generally the rhythm profile of the patients was not taken into consideration for the decision to treat. Proarrhythmic effects, accordingly, were also not assessed. Individual treatment and dosage adjustment by monitoring with effectiveness criteria was carried out in one study only in which, even here, criteria for effectiveness were arbitrarily capable of eliciting antiarrhythmic actions. Calculation of mortality rates was carried out on the basis of the total number of deaths in the respective groups without taking into consideration that by the end of the study, in the treatment group the medication had been discontinued in up to 40% of the patients. STUDIES WITH CLASS II DRUGS: For treatment with beta-receptor blockers there are 15 large, controlled, randomized, long-term studies available in which total mortality and the incidence of sudden cardiac death were studied.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2188896 TI - Direct neural effect of lateral hypothalamic stimulation on insulin secretion by pancreases of normal and obese rats. AB - Perfusion of CNS intact pancreases with 200 mg/dl glucose with concomitant lateral hypothalamic area (LHA) stimulation significantly inhibited insulin secretion both in normal and obese rats. Sprague-Dawley, Zucker lean (FaFa) and Zucker obese (fafa) rats all responded in a similar manner, suggesting a general effect unrelated to metabolic state. Insulin secretion during mins 25-40 of perfusion was inhibited in Sprague Dawley, lean Zucker and obese Zucker rats by 31%, 42% and 33%, even though LHA stimulation took place from mins 20-25. Thus, the duration of inhibition was greater than the period of LHA stimulation, indicating that this pathway can induce prolonged changes in the responsiveness of the pancreas. The data presented in this study demonstrate that LHA stimulation, in the absence of humoral factors, results in a direct CNS-mediated suppression of insulin secretion which is relatively long lasting. This effect may illustrate a basic control mechanism by the CNS to regulate the endocrine pancreas. PMID- 2188897 TI - Effect of insulin pump therapy on blood pressure and the renin-angiotensin system of diabetic rats. AB - Insulin therapy, administered by continuous subcutaneous infusion with osmotic pumps over a 28 day period at doses of 2.5 and 5.0 units/day, resulted in a statistically significant increase in body weight of diabetic rats. The concentration of blood glucose was reduced by 68% to 109 mg/dl blood sugar by the higher dose of insulin and only partial control of diabetes was achieved by the lower dose (185 mg/dl blood sugar, -39%). Blood pressure was normalized by both doses of insulin. Elevated serum angiotensin converting enzyme activity and plasma renin activity, expressed as generated angiotensin I, were unaffected by the lower dose of insulin, but were reduced by 26% and 40%, respectively at the higher dose. These data suggest that elevated serum ACE and plasma renin activity, commonly found in the streptozotocin-diabetic rat, may not be primarily responsible for hypertension in this model. PMID- 2188898 TI - Biological activity of nasally administered insulin in normal subjects. AB - Nasally administered (IN) insulin has been advocated as a potentially useful alternative to subcutaneously administered regular insulin because of its more rapid onset and time to peak action and its shorter duration of action. This study further defines the pharmacodynamics of IN insulin by using a euglycemic clamp technique to determine the bioavailability of IN insulin as compared with intravenous (IV) insulin, and to ascertain whether multiple sequentially administered doses of IN insulin alter pharmacodynamics. Eight normal volunteers received 2 control doses of IV insulin (0.05 U/kg), and 3 high doses (0.7 U/kg) and 3 low doses (0.35 U/kg) of IN insulin with an absorption enhancer (tauro 24,25 dihydrofusidate) given sequentially over a 2 day period. A euglycemic clamp was performed with a Biostator (Ames) that infused dextrose to keep the subject's blood glucose at his fasting level. Analysis of dextrose infusion curves for the low and high doses of IN insulin revealed an onset of action of 9.4 +/- 0.4 and 10.5 +/- 0.3 minutes, time to peak action of 20.6 +/- 5.6 and 23.7 +/- 4.4 minutes and duration of action of 82.1 +/- 5.2 and 95 +/- 5.7 minutes respectively. Both the onset of action and time to peak action were slightly longer (P less than .05) for the high as compared with the low dose IN insulin, although this should not represent a clinically significant difference. The total dextrose requirement was 21.9 +/- 2.3 g for the low dose IN insulin and 34.1 +/- 3.3 g for the high dose IN insulin, the latter value being significantly greater (P less than .01) than the former.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188899 TI - The evaluation of cortical bone remodeling with a new ultrasonic technique. AB - Total hip arthroplasty causes biomechanical changes in the normal femur including a redistribution and concentration of stress. These mechanical alterations in the femur cause local remodeling and resorption that affect the geometry and mechanical properties of the bone. Three complementary techniques were used to study the local adaptive remodeling of bone due to prosthesis implantation. A graphics package was used to obtain section geometrical information, an ultrasonic wave propagation technique to determine elastic properties, and a new scanning acoustic microscope (SAM) to map the acoustic impedance profile of each section. The effects of the implantation of two different types of hip prostheses were investigated, an uncemented bipolar prosthesis with an Austin-Moore type stem and a cemented Charnley prosthesis. Prosthesis implantation resulted in an increase in cortical area and mediolateral diameter and a decrease in anterio posterior diameter. Both prostheses had a detrimental effect on local elastic properties as determined by acoustic velocity measurements. Finally, the SAM system provided information about local inhomogeneities in bone properties not obtainable by any other means. The acoustic impedance maps highlighted bone resorption and bone remodeling on a microstructural level. PMID- 2188900 TI - Ventricular volume measurement from a multiplanar transesophageal ultrasonic imaging system: an in vitro study. AB - We have developed a system to assess the feasibility of using multiple transesophageal ultrasonic images to measure left-ventricular volume, an important variable in patient management. The system includes a special transesophageal probe with a micromanipulator for acquiring cardiac images in multiple planes with known interplanar spatial relationship and an off-line processing system to compute the volume. In vitro studies with the probe demonstrated that the distance between two targets in space can be identified within 2 mm (SD = 0.4 mm) for points in the imaging plane 3.4 mm (SD = 0.5 mm) for points not lying in the imaging plane. This gives an average accuracy of +/- 6.5% for distances greater than 4.5 cm. Comparison of ultrasonic measurements of the volume of water-filled balloons and excised hearts to the volume required to fill them, revealed a correlation coefficient of 0.992, a regression line having a slope of 1.0 and an ordinate intercept at 0.2 mL, and a standard error of the estimate of 8 mL. PMID- 2188901 TI - Ultrasonic two-axis rotation detector. AB - A two-axis rotation monitor is described which determines the relative displacement between a pair of ultrasonic detectors using the phase difference of a continuous ultrasound wave generated by a single, distant source. The monitor has been used to measure head rotations around the vertical and horizontal axes, but can easily be adopted to other body segment rotations or translations. The device produces high sensitivity recordings of wide spatial and dynamic range. Although the device is quite linear with good isolation between channels, a computer-based linearization/calibration routine is described which further increases linearity and reduces crosstalk. The device is unobtrusive, inexpensive, and has proven reliable and easy to use. PMID- 2188902 TI - A new glucose-clamp algorithm--theoretical considerations and computer simulations. AB - The commonly used setup of an automatic glucose-clamp was analyzed as a control system, modeling the measuring device and the patient in a simple but effective way. Strict limits in response time, parasitic oscillation amplitude, and accuracy were defined in order to approach the physician's requirements. We developed a new control algorithm and defined the gain coefficients which can lead the system within these limits. Computer simulations with model parameters from literature (patient) and from experimental data (measuring device) are presented. Preliminary in vivo trials are also presented. PMID- 2188903 TI - Effect of human recombinant interleukin-6 on the proliferation of mouse hepatocytes in the primary culture. AB - Effects of various cytokines on the proliferation of mouse hepatocytes were investigated. Human recombinant IL-6 not only enhanced the proliferation of mouse hepatocytes in the presence of epidermal growth factor, but also without epidermal growth factor. However, other human or mouse cytokines such as recombinant IL-1, IL-2, IL-3, IL-4, IFN-beta and IFN-gamma, which are known to regulate immune responses and/or hematopoiesis, had no effect on the proliferation of hepatocytes. These results suggest that IL-6 plays a crucial role in regulating the regeneration of hepatocytes after hepatitis or partial hepatectomy. PMID- 2188904 TI - Immunopathological changes in kidney in Plasmodium falciparum malaria. AB - Fifteen (34.8%) of 43 patients of falciparum malaria screened for urinary abnormalities showed significant proteinuria (greater than 150 mg/24 h), haematuria (greater than 1/HPF) and casts, with or without azotaemia. Light microscopic examination of renal biopsy tissue from 12 patients revealed mesangial and endothelial proliferative change in 8, and acute tubular necrosis in one patient. Immunofluorescence showed IgM alone, or IgG and IgM along with C3, in 7 patients within the mesangium or along the capillary walls. Repeat kidney biopsy after 6 wk in 5 patients revealed no residual pathology indicating the reversible nature of the lesions. PMID- 2188905 TI - Efficacy of two different DEC regimens in the treatment of human filarial infection. AB - Two regimens of diethyl carbamazine (DEC) viz., 14 day and 5 day, were compared for microfilaricidal effect and side effects, in the treatment of bancroftian filariasis. The rate of successful treatment, cure rate and decrease in mf count were found to be significantly high with the 14 days regimen when assessed immediately after treatment. About 40 per cent of subjects on the 14 days regimen and 66 per cent of patients on 5 days regimen experienced side reactions. The severity of side reactions was more in patients on 5 days regimen. When the effect of DEC was assessed one year after treatment with the 14 days regimen and compared with the results immediately after treatment, the rate of successful treatment, cure rate and decrease in mf count were reduced significantly. The 14 days DEC regimen with initial low dose of DEC along with antipyretics may be better accepted in the control programmes of filariasis. PMID- 2188906 TI - Differential recognition of Brugia malayi antigens by bancroftian filariasis sera. AB - Individuals residing in an area endemic to Wuchereria bancrofti infection were broadly categorised as endemic normals (EN), microfilaraemics (mf + ve) and elephantoids i.e., chronic lymphatic filariasis (EL). The immune status of these three groups was examined in terms of (i) specific antibody levels; (ii) ability to induce antibody dependent cellular cytotoxicity (ADCC) to microfilariae; and (iii) ability to recognise different microfilarial antigens by immunoblotting. All three groups of endemic residents were indistinguishable in their antibody levels as measured by ELISA with B. malayi microfilarial antigen. Many endemic normal sera and most elephantoid sera exerted strong cytotoxicity against W. bancrofti microfilariae whereas none of the mf + ve sera had any such activity. Immunoblotting studies revealed that a protein with mol. wt of 79 KDa was the only one among the proteins of B. malayi microfilarial extracts that was consistently recognised by sera from all endemic residents. Endemic normal sera and elephantoid sera, which exerted maximum cytotoxicity, together specifically recognised three proteins with molecular weights 25, 58 and 68 KDa and these three proteins could be among the candidate antigens that induce resistance to filarial infection. PMID- 2188907 TI - Effects of plumbagin on antibiotic resistance in bacteria. AB - Plumbagin, a compound derived from the roots of Plumbago zeylanica (Chitramool) was studied for its effect on the development of antibiotic resistance using antibiotic sensitive strains of Escherichia coli and Staphylococcus aureus. A delayed growth was seen when these organisms were inoculated into the antibiotic (streptomycin/rifampicin) medium, due to development of resistance in some of the cells. However, the growth was completely prevented when the bacteria were grown in the medium containing antibiotic and plumbagin together, and this was attributed to prevention of development of antibiotic resistant cells. PMID- 2188908 TI - Detection of early dividing forms of Plasmodium falciparum in peripheral blood. AB - P. falciparum schizonts were found in peripheral blood of six malaria patients including two infants who were moderately ill, with parasitaemia ranging from 33920 to 410800 per cubic mm. The patients lived in villages located at an altitude of 680 m and the phenomenon was observed during the cold season when transmission was high. Appearance of these forms was independent of host age. PMID- 2188909 TI - Cultivation of a nocardioform acid-fast chemoautotrophic bacterium from armadillo tissues infected with Mycobacterium leprae. AB - A nocardioform bacterium was isolated from the spleen tissue of an armadillo infected with M. leprae and easily propagated in pure culture in mineral salt medium supplemented with only simple C and N sources (e.g., liquid paraffin, tetradecane, ammonium salts, urea, asparagine, gelatin, xanthin, hypoxanthin etc.). Complex organic substances, e.g., tyrosin, casein, peptone, meat extract, egg proteins, serum, blood, yeast extract as well as medium 199, did not support the growth of this organism. Microscopically, the organism consisted of acid fast, long, slender rods which originated from long, fragmented hyphae, or sporulating mycelial tufts; it was acid-fast (at less than 4.0% H2SO4) which was pyridine-susceptible. It produced DOPA-oxidase and Catalase and was lysozyme resistant; this grew best under reduced O2 tension, at pH 7.0 to 8.0 and 28 degrees C. Serologically, it appeared to be only weakly related to the prototype human multibacillary leprosy-derived (reference) nocardioform strain, Nocardia brasiliensis and N. caviae, but was variably related to several mycobacteria strains. PMID- 2188910 TI - Evaluation of the Hamilton-Thorn 2030 motility analyser for routine semen analysis in an infertility clinic. AB - In routine semen analysis of 242 patients the values of sperm concentration, sperm motility and progressive sperm motility were measured with the Hamilton Thorn semen analyser (HT) and compared to the data obtained by conventional semen analysis according to the guidelines of the WHO. Overall, the HT gave higher values for sperm concentration (mean difference 21.7 +/- 46.2 x 10(6) ml-1, mean +/- SD). Motility values showed a correlation of 0.67 (slope 0.94, P less than 0.001) but were estimated lower by the HT than by conventional analysis (mean difference 7.3 +/- 21.7%); this was caused by the overestimation of sperm concentration. In the range from 0 to 50% motility the HT yielded lower values and higher values from 50 to 100% motility. Progressive motility values of the HT agreed better with conventional analysis (WHO categories a + b): the mean difference of all values was 0.5 +/- 19.5% (r = 0.74, slope = 1.0). The mean lateral head displacement measured by the HT increased with increasing sperm path velocity, but other significant correlations between sperm movement parameters could not be demonstrated. In many instances round cells and debris could not be distinguished from normal sperm. In conclusion, the HT system cannot replace conventional semen analysis in routine diagnosis. PMID- 2188911 TI - Computer aided interpretation of acid-base disorders. AB - This paper describes an expert system for the interpretation of acid-base disorders. The target users are residents in training in internal medicine, anaesthesia and intensive care medicine. The program is written in PROLOG and runs on a SUN 3/160 minicomputer. Evaluation of a learning set (N = 202) and a test set (N = 194) has proved that the system's accuracy is acceptable. As a result, the program has recently been put in routine clinical practice. PMID- 2188912 TI - The recent development and evaluation of a medical expert system (ABVAB). AB - A medical expert system for the diagnosis of abnormal vaginal bleeding named as ABVAB had been reported. This paper will describe the recent development of ABVAB and its clinical evaluation. The overall testing results are quite satisfactory in spite of the limitations of time and small domain. This expert system, by using the fuzzy and certainty factor concepts, is able to handle imprecise and incomplete medical knowledge which has become informative. The paper also analyses the relative degrees of importance of the history and physical examination data in making a medical diagnosis. PMID- 2188913 TI - Conformationally restricted peptides through short-range cyclizations. AB - The various types of conformationally restricted peptides obtained by short-range cyclizations, from residue i to residue i + 1, are presented. Relevant examples of N in equilibrium C alpha, C' in equilibrium C alpha, N in equilibrium C', C alpha in equilibrium C alpha, C' in equilibrium C', and N in equilibrium N cyclizations are reported and the pertinent literature listed. In the discussion emphasis is place on the conformational consequences for peptides from the incorporation of such ring structures. PMID- 2188914 TI - Magnitude and causes of blindness in the developing world. PMID- 2188915 TI - High volume efficient cataract surgery in developing countries. AB - The use of simple, flexible, efficient eye departments which make good use of available personnel and appropriate technology can be a very effective method of offering eye care and cataract surgery to large numbers of patients in the tropics and elsewhere. Such a department in a village hospital in Pakistan is described as an example of how effective such an approach can be in the delivery of cataract surgery and other eye care. PMID- 2188916 TI - The choice of cataract surgical techniques in developing nations: operations research considerations. PMID- 2188918 TI - Appropriate eye drugs for developing countries. PMID- 2188917 TI - Ocular problems in AIDS. PMID- 2188919 TI - Onchocerciasis in Zaire. AB - The first mention in Africa of ocular lesions and of blindness due to onchocerciasis was made by Hissette in Zaire in 1931, although the disease had already been known there since 1903. On a map of Zaire were indicated all the known data of the geographical distribution of onchocerciasis: data from the literature, from field work and from the patients seen in Kinshasa. An estimation of the relative incidence of the disease was made by comparing the number of patients with the number of the latest population census for each administrative zone. The environmental and developmental factors determining the epidemiological aspects are discussed. The clinical aspects of the typical eye symptoms are reviewed. Their correlation with age, with immunology and with some specialized eye examinations are discussed. PMID- 2188920 TI - Onchocerciasis. AB - Onchocerciasis is a devastating blinding disease caused by the parasite Onchocerca volvulus that infects about 80 million people, causing blindness and visual impairment in 1-2 million people. In hyperendemic areas, more than half of the population will become blind from onchocerciasis before they die. Blindness is the most important effect of the disease and results, in part, from direct invasion of the eye by microfilariae. The recent development of ivermectin has revolutionized our ability to treat this disease. An annual oral dose of only 150 mg/kg completely suppresses the disease manifestations. Programs for the community-based mass distribution of ivermectin are now being conducted and promise to control this major blinding scourge. PMID- 2188921 TI - Xerophthalmia, keratomalacia and nutritional blindness. AB - Vitamin A deficiency remains a major cause of pediatric ocular morbidity. Over five million children develop xerophthalmia annually, a quarter million or more becoming blind. It is also a major pathway for measles-associated blindness, particularly in Africa. Treatment is practical and inexpensive, based upon the oral administration of 200,000 IU vitamin A on two successive days, at a cost of 10 cents U.S. Given the potential rapidity of corneal necrosis (keratomalacia) and the relative inaccessibility of health services to those at greatest risk, prevention is probably more important than treatment. Oral administration of high dose supplements (2000,000 IU every 3 to 6 months), vitamin A fortification of commonly consumed items, or best of all, increased dietary intake of natural sources of vitamin A will reduce the number of needlessly blind young children. Given recent evidence that vitamin A deficiency greatly increases overall mortality, even among children without evidence of xerophthalmia, the same prophylactic regimen may improve child survival by 35% or more. PMID- 2188922 TI - Trachoma. AB - Trachoma causes one-quarter of the world's blindness and, although it has disappeared from many developed areas, it remains a major problem, especially in underprivileged rural areas in developing countries. Recent advances in the understanding of the molecular biology of chlamydia offer encouragement for the eventual development for an effective trachoma vaccine. Advances in the understanding of the epidemiology of trachoma, particularly of the importance of reinfection and the intrafamily transmission of infection, have led to the identification of the key importance of simple hygiene measures such as facial cleanliness in preventing the transmission of trachoma. Community-based health education intervention programs are being developed to assess the efficacy of a public health approach to the control of trachomatous blindness. PMID- 2188923 TI - The promise of international eye banking. AB - According to the World Health Organization, world blindness has been put between 28 to 42 million. Of this number, well over 10 million are corneally blind. Tissue Banks International, TBI, through its international division known as the International Federation of Eye Banks, IFEB, is assisting in establishing regional eye banks on a global basis. The experiences of TBI in the United States have provided a model system of eye banking and, as an outgrowth of this system, an international network may be established. It is hoped that this international network of eye banks will generate eye tissue which can be shared with those parts of the world where no eye banking system currently exists. PMID- 2188924 TI - The World Health Organization's programme for the prevention of blindness. PMID- 2188925 TI - Aclacinomycin A in the treatment of multiple myeloma: a Southwest Oncology Group study. AB - Fifty-two patients with progressive resistant multiple myeloma were entered in this Southwest Oncology Group Phase II study, using weekly intravenous Aclacinomycin A. Of forty-three evaluable patients for response, there was one partial remission of 2 years duration and two sustained clinical improvements with 25% reduction in paraprotein. Major toxicity seen was severe myelosuppression and significant nausea and vomiting requiring dose reduction and delay of the scheduled treatment. Cardiac arrhythmia was seen in one patient. Chronic daily schedule or continuous IV infusion is recommended for future study. PMID- 2188926 TI - Phase II trial of 6-diazo-5-oxo-L-norleucine versus aclacinomycin-A in advanced sarcomas and mesotheliomas. AB - Ninety-eight patients with previously-treated advanced soft tissue sarcoma, bone sarcoma, or mesothelioma were randomly assigned to one of two intravenous single agent treatment regimens, either 6-diazo-5-oxo-l-norleucine (DON; brief infusions of 50 mg/m2/day for 5 consecutive days every 4 weeks) or aclacinomycin-A (ACM-A, as 30-min infusions of 100 mg/m2 or 85 mg/m2, administered every 3 weeks). Of 43 patients who were evaluable for response, survival and toxicity, there were two responses (5%) produced by ACM-A; one in a male with mesothelioma, and one in a female with malignant fibrous histiocytoma. None of the 36 evaluable patients treated with DON developed an objective tumor response. Median survival was 4.8 months in the DON treatment arm, and 6.8 months in the ACM-A treatment arm. No patients on the DON arm experienced lethal or life-threatening toxicities, and severe toxicities resulting from this treatment included nausea and emesis (10%), stomatitis (2%), gastrointestinal toxicity (2%), and anemia (2%). Moderate toxicities included vomiting (24%), hematologic toxicity (24%), neurologic toxicity (7%), diarrhea (7%), mucositis (5%), fever (5%), palpitations (2%), hepatotoxicity (2%), bleeding (2%) and edema (2%). Fifteen percent experienced at least one severe reaction, and 63% experienced at least one moderate or greater toxicity. ACM-A was associated with four cases of life-threatening myelosuppression (7%); severe toxicities included myelosuppression (11%), neurologic toxicity (4%), diarrhea (2%), respiratory toxicity (2%), pain and muscle spasms (2%), edema (2%), and ulceration following extravasation (2%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188927 TI - Discrepancy between cytotoxicity and DNA interstrand crosslinking of carboplatin and cisplatin in vivo. AB - We used the method of alkaline elution to compare quantitatively the DNA lesions produced by cisplatin and carboplatin in the AKR leukemia in vivo. These data were compared with cytotoxicity of each drug in the same animal model and in a solid tumor murine model (colon 26). DNA-protein and DNA-DNA interstrand crosslinks were formed in similar proportions by both drugs when peak values of crosslinking were compared. No clear difference in the rate of formation of both types of crosslinks could be observed between these drugs. On a molar basis a 3- to 4-fold more carboplatin had to be given to obtain equivalent frequencies of both types of crosslinks. In contrast, to obtain equitoxicity in the same animal tumor model, 13 fold higher doses of carboplatin had to be given. This difference in cytotoxicity between both drugs is comparable to the difference measured in colon 26 in vivo (16 fold). Both values are in the range of literature data (10 25 fold) dealing with the relative potency of cisplatin and carboplatin in murine tumor models. PMID- 2188928 TI - Phase II evaluation of mitoxantrone in advanced pancreatic carcinoma: a Southwest Oncology Group study. AB - Patient with advanced adenocarcinoma of the pancreas and no prior chemotherapy were treated on a Phase II trial of mitoxantrone. Doses were adjusted for hepatic dysfunction as defined by bilirubin. Twenty-four patients with a bilirubin less than or equal to 1.5 mg% received mitoxantrone 12 mg/m2 i.v. repeated every three weeks. Myelosuppression in the form of leukopenia was the major toxicity. There were no responses in twenty-four evaluable patients. PMID- 2188929 TI - Phase II evaluation of esorubicin (4'deoxydoxorubicin) in pancreatic adenocarcinoma: a Southwest Oncology Group study. AB - Esorubicin (4' deoxydoxorubicin) is a new analogue of the anthracycline, doxorubicin. This compound lacks the hydroxyl group at 4' position on the amino sugar of the anthracycline. Phase II study was designed to determine the clinical response rate and to define the qualitative and quantitative toxicities of esorubicin in patients with adenocarcinoma of the pancreas. Fifty-eight patients with inoperable adenocarcinoma of the pancreas were entered on the study, 47 were evaluable for response, and 57 were evaluable for toxicity. The dose of esorubicin was 30 mg/m2 for good risk patients and 25 mg/m2 for poor risk patients every 21 days and administered IV push through a side arm of a running IV. Diphenhydramine, 50 mg is administered IM prior to the administration of the drug to block local venous reaction. Subsequent doses of esorubicin were modified according to granulocyte and platelet nadirs and the drug was not administered until recovery of platelets (greater than 100,000/microliters) and wbc (greater than 3000/microliters). Three partial responses, 20 stable, and 31 with increased disease were observed. Forty-seven had severe granulocytopenia (less than 250), and two patients had severe thrombocytopenia (less than 25,000). One patient experienced a decrease in left ventricular ejection fraction with a total dose of 180 mg/m2. The dose of esorubicin in this study demonstrated that the drug has minimal activity in adenocarcinoma of the pancreas but the toxicity is tolerable. Search should continue for single agents with activity in this disease. PMID- 2188931 TI - The role of imaging in screening for prostate cancer. A decision analysis perspective. AB - Using Bayesian and decision analytical concepts, we can define the ideal characteristics of any screening test for cancer of the prostate: high specificity, reasonably high sensitivity, noninvasiveness, low cost, and low interobserver variability. Computed tomography (CT) fails as a test, since it cannot show the internal structure of the prostate; MRI is too expensive and has an unacceptably poor specificity. Transrectal sonography does have many desirable characteristics, including relatively high sensitivity and, if no biopsy is done, low cost and noninvasiveness. But it has an unacceptably low specificity for early, clinically significant lesions: over half of all patients tested will have a positive result, requiring a confirming biopsy, which means that transrectal sonography will in the end be too invasive and too expensive. Therefore, we cannot recommend transrectal sonography as a primary screening tool for cancer of the prostate at this time. PMID- 2188930 TI - VM-26 in colorectal carcinoma: a Southwest Oncology Group study. AB - In this multi-institutional phase II study, VM-26 or Teniposide was administered to forty-two patients with advanced colorectal cancer. Patients were initially treated at 60 mg/M2 daily for 5 days with dose adjustments depending on toxicity. One complete response and one partial response were observed lasting six and four months respectively. Leukopenia was severe in 40% of patients. No drug related deaths were seen. In this Southwest Oncology Group (SWOG) study, VM-26 appeared to have minimal benefit in advanced colorectal cancer. PMID- 2188933 TI - [Acanthokeratolytic epidermal nevus: acanthokeratolysis is hereditary, not the nevus]. AB - Epidermal naevus of the acanthokeratolytic (epidermolytic) type is a mosaic birth defect. The underlying mutation may also be present in the gonads and can then be transmitted to the next generation. The affected child, however, will always show a diffuse involvement of the entire body in the form of bullous congenital ichthyosiform erythroderma. In other words, the phenotype can be transmitted, but not the mosaic. This explains why acanthokeratolytic epidermal naevus always affects the parent and never the child when it is observed in a family together with bullous congenital ichthyosiform erythroderma. PMID- 2188932 TI - Malignancies metastatic to the pleura. AB - In patients over 50 years of age, neoplasms of the pleura are probably the second most common cause of a pleural effusion after congestive heart failure. Lung cancer, breast cancer, lymphoma, ovarian carcinoma, and stomach cancer are the leading causes of malignant pleural disease, and adenocarcinoma is the most common cell type. This review discusses in detail the etiology and incidence, pathogenesis, clinical manifestations, diagnosis, prognosis, and treatment of neoplasms that involve the pleura with special reference to malignant and paramalignant pleural effusions. PMID- 2188934 TI - [Local treatment with corticosteroids--limits on the duration of administration]. AB - In local therapy with corticosteroids, undesirable effects are closely related to the duration of the treatment. These interactions are even more evident if the tolerance of different corticosteroids varying in strength of action is examined and referred to the duration of application. For example, symptoms of epidermal atrophy may occur even after as little as 4 weeks' treatment with very potent antiproliferative corticosteroids, whereas with the only moderately active hydrocortisone, which has an exclusively anti-inflammatory effect, these symptoms are hardly observed even after 10 weeks of application. The question of the origin of these undesirable effects is considered in post-marketing studies, for example, and in particular the question of when they are attributable, solely to the vehicle and when to the corticoid itself, is discussed. In addition, an attempt is made to classify the corticosteroids into those for which the permissible duration of treatment must be specified in the package insert and those for which this does not seem necessary. In this connection, the treatment periods required with fixed combinations are discussed with reference to the basic skin disease. Finally, the duration of treatment when application is limited to certain cutaneous areas or to a certain size of skin area or when the treatment is self-prescribed is discussed. PMID- 2188935 TI - [Leprosy. Pathogenesis--classification--diagnosis--treatment]. AB - Leprosy (hanseniasis) is caused by chronic infection with Mycobacterium leprae (M. leprae). The disease involves primarily the superficial peripheral nerves and the skin, but almost any organ can be affected. The clinical features vary and are determined by the host's immune response to the infection. A distinction is made between multibacillary and paucibacillary forms of leprosy. The multibacillary forms are lepromatous, borderline-lepromatous and borderline borderline leprosy; the paucibacillary forms are tuberculoid and borderline tuberculoid leprosy. The clinical features and the histological picture depend on the patient's immune response. Because effective chemotherapy has become available, leprosy can now be cured, and frightening disabilities are therefore preventable. PMID- 2188936 TI - [Morphaea profunda]. AB - A 47-year-old woman with a solitary morphoea profunda on the flexor aspect of the left thigh is described. Clinically the lesion is characterized by a circumscribed, deeply indurated sclerotic plaque. The main histopathological features were sclerotic collagen changes and a striking accumulation of inflammatory cells in the deep dermis as well as in the subcutaneous tissue. Plasma cells and T- and B-lymphocytes were the predominant cellular components of the infiltrate. The patient had an elevated serum titre of antibodies to Borrelia burgdorferi. The patient was treated with penicillin, which brought about a remarkable improvement. These findings provide further support for the concept that in some cases morphoea profunda may be a manifestation of Borrelia infection. PMID- 2188937 TI - [Acquired acral fibrokeratoma]. AB - A 33-year-old man with an acral fibrokeratoma of the finger. Clinical, anamnestic, histopathologic and immunohistological findings suggest a traumatically induced connective tissue hyperproliferation with secondary epidermal hyperplasia in this benign fibroepithelial tumour. PMID- 2188938 TI - [Johann Lucas Schonlein (1793-1864), a researcher and clinician]. AB - From 1833 to 1840, Johann Lucas Schonlein, a native of Bamberg, Germany, was Professor of Internal Medicine at the newly created University of Zurich, Switzerland. His career and professional personality are described succintly in this paper. Schonlein was a most successful clinical teacher. He was the first German professor to teach at Wurzburg, 1819-1832) clinical percussion and auscultation. On the other hand, he obviously hated writing and publishing. His 3 important discoveries, all made during his years in Zurich, were published on a total of 3 printed pages: so-called typhoid crystals in patients' stools (1836), "peliosis rheumatica" (1837), and - most important - the causative agent of favus (1839), a fungus later named Achorion schoenleinii. This was the first instance of a human disease that could be clearly attributed to the action of a micro organism. PMID- 2188939 TI - [Exlibris of famous dermatologists]. AB - The significance of bookplates as documents for history of medicine is illustrated by reference to bookplates of famous dermatologists: Conrad Heinrich Fuchs, William Erasmus Wilson, Moriz Kaposi, Filipp Josef Pick, Ludwig Waelsch, Edvard Ehlers. PMID- 2188941 TI - Physical map location of the tdc operon of Escherichia coli. PMID- 2188940 TI - In vitro induction of the fat-storing phenotype in a liver connective tissue cell line-GRX. AB - Liver connective tissue cells have been characterized as perisinusoidal myofibroblasts and hepatic lipocytes (Ito cells, fat-storing cells). A concept of a single mesenchymal cell population that may be modulated between these two phenotypes has been postulated. We have previously established a continuous murine cell line, GRX, obtained from fibrotic granulomatous lesions induced by schistosomal infection in mouse liver. This cell line is considered to represent liver myofibroblasts. In the present study we have induced the conversion of these cells into lipocyte (fat storing) phenotype by treatment with insulin and indomethacin. We have quantified the lipid synthesis and the increase of activity of involved enzymes during the induction of the fat-storing phenotype and described modifications of cell organization along this modulation of cell functions. PMID- 2188942 TI - Escherichia coli metR mutants that produce a MetR activator protein with an altered homocysteine response. AB - Using an Escherichia coli lac deletion strain lysogenized with a lambda phage carrying a metH-lacZ gene fusion, we isolated trans-acting mutations that result in simultaneous 4- to 6-fold-elevated metH-lacZ expression, 5- to 22-fold-lowered metE-lacZ expression, and 9- to 20-fold-elevated metR-lacZ expression. The altered regulation of these genes occurs in the presence of high intracellular levels of homocysteine, a methionine pathway intermediate which normally inhibits metH and metR expression and stimulates metE expression. P1 transductions and complementation tests indicate that the mutations are in the metR gene. Our data suggest that the mutations result in an altered MetR activator protein that has lost the ability to use homocysteine as a modulator of gene expression. PMID- 2188943 TI - Isolation and characterization of a new mutant of Saccharomyces cerevisiae with altered synthesis of 5-aminolevulinic acid. AB - A new gene, RHM1, required for normal production of 5-aminolevulinic acid by Saccharomyces cerevisiae, was identified by a novel screening method. Ethyl methanesulfonate treatment of a fluorescent porphyric strain bearing the pop3-1 mutation produced nonfluorescent or weakly fluorescent mutants with defects in early stages of tetrapyrrole biosynthesis. Class I mutants defective in synthesis of 5-aminolevulinate regained fluorescence when grown on medium supplemented with 5-aminolevulinate, whereas class II mutants altered in later biosynthetic steps did not. Among six recessive class I mutants, at least three complementation groups were found. One mutant contained an allele of HEM1, the structural gene for 5-aminolevulinate synthase, and two mutants contained alleles of the regulatory gene CYC4. The remaining mutants contained genes complementary to both hem1 and cyc4. Mutant strain DA3-RS3/68 contained mutant gene rhm1, which segregated independently of hem1 and cyc4 during meiosis. 5-Aminolevulinate synthase activity of the rhm1 mutant was 35 to 40% of that of the parental pop3-1 strain, whereas intracellular 5-aminolevulinate concentration was only 3 to 4% of the parental value. Transformation of an rhm1 strain with a multicopy plasmid containing the cloned HEM1 gene restored normal levels of 5-aminolevulinate synthase activity, but intracellular 5-aminolevulinate was increased to only 9 to 10% of normal. We concluded that RHM1 could control either targeting of 5 aminolevulinate synthase to the mitochondrial matrix or the activity of the enzyme in vivo. PMID- 2188944 TI - SecY, a multispanning integral membrane protein, contains a potential leader peptidase cleavage site. AB - SecY is an Escherichia coli integral membrane protein required for efficient translocation of other proteins across the cytoplasmic membrane; it is embedded in this membrane by the 10 transmembrane segments. Among several SecY-alkaline phosphatase (PhoA) fusion proteins that we constructed previously, SecY-PhoA fusion 3-3, in which PhoA is fused to the third periplasmic region of SecY just after the fifth transmembrane segment, was found to be subject to rapid proteolytic processing in vivo. Both the SecY and PhoA products of this cleavage have been identified immunologically. In contrast, cleavage of SecY-PhoA 3-3 was barely observed in a lep mutant with a temperature-sensitive leader peptidase. The full-length fusion protein accumulated in this mutant was cleaved in vitro by the purified leader peptidase. A sequence Ala-202-Ile-Ala located near the proposed interface between transmembrane segment 5 and periplasmic domain 3 of SecY was found to be responsible for the recognition and cleavage by the leader peptidase, since a mutated fusion protein with Phe-Ile-Phe at this position was no longer cleaved even in the wild-type cells. These results indicate that SecY contains a potential leader peptidase cleavage site that undergoes cleavage if the PhoA sequence is attached carboxy terminally. Thus, transmembrane segment 5 of SecY can fulfill both of the two important functions of the signal peptide, translocation and cleavage, although the latter function is cryptic in the normal SecY protein. PMID- 2188945 TI - Cloning and nucleotide sequences of the genes for the subunits of NAD-reducing hydrogenase of Alcaligenes eutrophus H16. AB - The genes hoxF, -U, -Y, and -H which encode the four subunit polypeptides alpha, gamma, delta, and beta of the NAD-reducing hydrogenase (HoxS) of Alcaligenes eutrophus H16, were cloned, expressed in Pseudomonas facilis, and sequenced. On the basis of the nucleotide sequence, the predicted amino acid sequences, and the N-terminal amino acid sequences, it was concluded that the structural genes are tightly linked and presumably organized as an operon, denoted hoxS. Two pairs of 24 and -12 consensus sequences resembling RpoN-activatable promoters lie upstream of hoxF, the first of the four genes. Primer extension experiments indicate that the second promoter is responsible for hoxS transcription. hoxF and hoxU code for the flavin-containing dimer (alpha and gamma subunits) of HoxS which exhibits NADH:oxidoreductase activity. A putative flavin-binding region is discussed. The 26.0-kilodalton (kDa) gamma subunit contains two cysteine clusters which may participate in the coordination of two [4F3-4S]centers. The genes hoxY and hoxH code for the small 22.9-kDa delta subunit and the nickel-containing 54.8-kDa beta subunit, respectively, of the hydrogenase dimer of HoxS. The latter dimer exhibits several conserved regions found in all nickel-containing hydrogenases. The roles of these regions in coordinating iron and nickel are discussed. Although the deduced amino acid sequences of the delta and beta subunits share some conserved regions with the corresponding polypeptides of other [NiFe] hydrogenases, the overall amino acid homology is marginal. Nevertheless, significant sequence homology (35%) to the corresponding polypeptides of the soluble methylviologen-reducing hydrogenase of Methanobacterium thermoautotrophicum was found. Unlike the small subunits of the membrane-bound and soluble periplasmic hydrogenases, the HoxS protein does not appear to be synthesized with an N-terminal leader peptide. PMID- 2188946 TI - Multiple translational products from a Mycoplasma hyorhinis gene expressed in Escherichia coli. AB - We analyzed protein expression from a cloned Mycoplasma hyorhinis genomic fragment that produces in Escherichia coli a set of related polypeptides of 110, 100, 65, and 55 kilodaltons from a coding region of just over 3.0 kilobases. Expression of these multiple products resulted from a mechanism operating at the translational level but not from truncation at UGA termination codons, which are known to encode tryptophan in several mycoplasma species. The structural relatedness of the proteins was demonstrated by two-dimensional tryptic peptic mapping, but their generation by posttranslational processing was ruled out by pulse-chase labeling analysis. Examination of proteins expressed from plasmid constructs and tryptic peptide analysis of these polypeptides and the original set of proteins revealed that they share carboxy-terminal regions, an observation inconsistent with truncation at UGA codons. Expression of proteins from this cloned fragment was not dependent on vector sequences and was observed when the coding region was placed under control of a T7 promoter, suggesting that all products were translated from a single message. Expression of related products in mycoplasmas was examined by immunoblot analysis of M. hyorhinis proteins with antiserum against overexpressed recombinant proteins. A single 115-kilodalton mycoplasma protein was detected, which is larger than any of the related proteins expressed in E. coli. Our analysis indicated that translation initiation sites are used in E. coli that are not active in mycoplasmas, thereby defining differences between the translational regulatory signals of mycoplasmas and eubacteria. PMID- 2188947 TI - Complementation of an Escherichia coli proC mutation by a gene cloned from Treponema pallidum. AB - Little is known concerning the biosynthetic and metabolic capabilities of the syphilis agent, Treponema pallidum, because of the inability to cultivate continuously the organism in vitro. To circumvent the problem of cultivation, researchers have used recombinant DNA technology to express treponemal protein antigens in Escherichia coli. However, with a few notable exceptions, the specific cellular roles of these cloned treponemal proteins have not been determined. In this study, a cosmid library of T. pallidum genomic DNA was constructed and amplified by repackaging infective lambda bacteriophage particles in vivo. Recombinant clones capable of complementing a null mutation in the E. coli proC gene encoding 1-pyrroline-5-carboxylate (P5C) reductase (EC 1.5.1.2) were subsequently identified. The complementing activity was eventually localized to a 2.3-kilobase BglII-HindIII fragment that hybridized to the same-size fragment of a BglII-HindIII digest of T. pallidum DNA. Two proteins of 41 and 27 kilodaltons (kDa) were encoded by this fragment, as determined by maxicell analysis. Although only the 41-kDa protein could be specifically precipitated by experimental syphilitic rabbit antisera, it was the 27-kDa protein that was responsible for the proC-complementing activity. The recombinant P5C reductase differed from the native E. coli enzyme by a number of biochemical properties. The cloning of a T. pallidum gene encoding P5C reductase strongly suggests that this pathogen has the ability to synthesize proline and possibly other amino acids. PMID- 2188948 TI - The folding properties of the Escherichia coli maltose-binding protein influence its interaction with SecB in vitro. AB - It has been proposed that the cytoplasmic SecB protein functions as a component of the Escherichia coli protein export machinery by serving as an antifolding factor that retards folding of the precursor maltose-binding protein (preMBP) into a translocation-incompetent form. In this study, it was found that SecB directly interacts with wild-type preMBP and various mutationally altered MBP species synthesized in vitro to form a SecB-MBP complex that can be precipitated with anti-SecB serum. The association of SecB with wild-type preMBP was relatively unstable; such a complex was formed only when SecB was present cotranslationally or after denaturation of previously synthesized preMBP and was detected with only low efficiency. In marked contrast, MBP species that were defective in the ability to assume the stable conformation of wild-type preMBP or that exhibited significantly slower folding kinetics formed much more stable complexes with SecB. In one case, we demonstrated that SecB did not need to be present cotranslationally for complex formation to occur. Formation of a complex between SecB and MBP was clearly not dependent on the MBP signal peptide. However, we were unable to detect complex formation between SecB and MBP lacking virtually the entire signal peptide but having a completely intact mature moiety. This MBP species folded at a rate considerably faster than that of wild-type preMBP. The propensity of this mutant protein to assume the native conformation of mature MBP apparently precludes a stable association with SecB, whereas an MBP species lacking a signal peptide but exhibiting altered folding properties did form a complex with SecB that could be precipitated with anti-SecB serum. PMID- 2188949 TI - RecA protein of Escherichia coli has a third essential role in SOS mutator activity. AB - The DNA damage-inducible SOS response of Escherichia coli includes an error-prone translesion DNA replication activity responsible for SOS mutagenesis. In certain recA mutant strains, in which the SOS response is expressed constitutively, SOS mutagenesis is manifested as a mutator activity. Like UV mutagenesis, SOS mutator activity requires the products of the umuDC operon and depends on RecA protein for at least two essential activities: facilitating cleavage of LexA repressor to derepress SOS genes and processing UmuD protein to produce a fragment (UmuD') that is active in mutagenesis. To determine whether RecA has an additional role in SOS mutator activity, spontaneous mutability (tryptophan dependence to independence) was measured in a family of nine lexA-defective strains, each having a different recA allele, transformed or not with a plasmid that overproduces either UmuD' alone or both UmuD' and UmuC. The magnitude of SOS mutator activity in these strains, which require neither of the two known roles of RecA protein, was strongly dependent on the particular recA allele that was present. We conclude that UmuD'C does not determine the mutation rate independently of RecA and that RecA has a third essential role in SOS mutator activity. PMID- 2188950 TI - Acetohydroxy acid synthase activity from a mutation at ilvF in Escherichia coli K 12. AB - Examination of the ilvF locus at 54 min on the Escherichia coli K-12 chromosome revealed that it is a cryptic gene for expression of a valine-resistant acetohydroxy acid synthase (acetolactate synthase; EC 4.1.3.18) distinct from previously reported isozymes. A spontaneous mutation, ilvF663, yielded IlvF+ enzyme activity that was multivalently repressed by all three branched-chain amino acids, was completely insensitive to feedback inhibition, was highly stable at elevated temperatures, and expressed optimal activity at 50 degrees C. The IlvF+ enzyme activity was expressed in strains in which isozyme II was inactive because of the ilvG frameshift in the wild-type strain K-12 and isozymes I and III were inactivated by point mutations or deletions. Tn5 insertional mutagenesis yielded two IlvF- mutants, with the insertion in ilvF663 in each case. These observations suggest that the ilvF663 locus may be a coding region for a unique acetohydroxy acid synthase activity. PMID- 2188951 TI - Lactobacillus hilgardii plasmid pLAB1000 consists of two functional cassettes commonly found in other gram-positive organisms. AB - A Lactobacillus hilgardii plasmid, pLAB1000, was studied to understand the organization of autonomous replicons from lactobacilli. Two cassettes could be identified. First, the replication region consisted of a sequence coding for a replication protein (Rep) and its corresponding target site, similar to those from plasmids pUB110, pC194 (Staphylococcus aureus), pFTB14, pBAA1 (Bacillus sp.), and pLP1 (Lactobacillus sp.). Sequence analysis indicated the possible synthesis of an antisense RNA that might regulate Rep production. The results also suggested that pLAB1000 replicates via a single-stranded DNA intermediate, and a putative lagging-strand initiation site was found that had similarities to those of alpha 3, St-1, and G4 isometric bacteriophages. The second cassette of pLAB1000 consisted of a sequence coding for a putative mobilization protein (Mob) and its corresponding RSA site. This cassette was similar to those found in pT181, pUB110, pE194 (S. aureus), and pG12 (Bacillus sp.), and it was found to be conserved among different Lactobacillus plasmid replicons. The origin and evolution of these functional cassettes are also discussed. PMID- 2188952 TI - Escherichia coli rna gene encoding RNase I: cloning, overexpression, subcellular distribution of the enzyme, and use of an rna deletion to identify additional RNases. AB - The cloning and overexpression of the Escherichia coli rna gene encoding RNase I are described. Only a single copy of the rna gene is present on the E. coli chromosome. Although cells with as much as a 100-fold increase in RNase I activity were constructed, little effect on cell growth was observed. Overexpressed RNase I was found in the periplasmic space to the same degree (approximately 85%) as wild-type enzyme, suggesting no limitation in RNase I transport. The rna clone was used to identify a deletion strain totally lacking the rna gene. The normal growth of this strain showed that RNase I is not essential for cell viability. Extracts from the RNase I deletion strain still retained a low level of RNase activity in the presence of EDTA, conclusively demonstrating the existence of additional EDTA-active RNases in E. coli. The possibility of a RNase I inhibitor is also discussed. PMID- 2188953 TI - Roles of the two lysyl-tRNA synthetases of Escherichia coli: analysis of nucleotide sequences and mutant behavior. AB - The complete nucleotide sequence of lysU, the gene for the heat-inducible lysyl tRNA synthetase of Escherichia coli, was determined and compared with the published sequence of lysS (herC), the gene for the constitutive lysyl-tRNA synthetase. These unlinked genes were found to be identical over 72% of their lengths. The deduced amino acid sequences of the respective gene products, LysU and LysS, were identical over 85% and similar over 92% of their lengths. Accumulation of high levels of LysU during growth of strains carrying the wild type allele of lysU on multicopy plasmids had no observable effect on growth or on the synthesis of LysS. A lysU deletion strain was constructed and was shown to grow normally at low temperature (28 degrees C) but poorly at 44 degrees C; the slow growth (45% of normal) at elevated temperature was fully reversed by plasmids bearing wild-type lysU. The implications of these findings for the existence of two aminoacyl-tRNA synthetases for lysine are discussed. PMID- 2188954 TI - In vivo cloning and characterization of the gabCTDP gene cluster of Escherichia coli K-12. AB - The gabCTDP gene cluster, which specifies and regulates synthesis of the gamma aminobutyrate (GABA) transport carrier, of glutamate-succinic semialdehyde transaminase, and of succinic semialdehyde dehydrogenase, responsible for the uptake and metabolism of gamma-aminobutyric acid in Escherichia coli K-12, was cloned in vivo, using the mini-Mu replicon bacteriophage Mu dI5086 as the vector. A subclone containing a 7.8-kilobase (kb) EcoRI-HindIII fragment complemented all of our Gab- mutants. By restriction mapping, this DNA fragment was located at kb 2800.5 to 2808.5 on the physical map of the E. coli K-12 chromosome. A subclone containing a 1.8-kb EcoRI-SalI fragment complemented the gab-repressed strain CS101A (wild-type gabC) but did not complement any gab structural gene mutants. The gab genes are divergently transcribed from promoters located in the vicinity of the unique BamHI site. Transcription in both directions is under dual control of catabolite repression and nitrogen regulation. Using a procaryotic DNA directed translation system, we observed three insert-coded polypeptide bands of 53 to 55, 45 to 48, and 40 to 43 kilodaltons (kDa). In vivo studies with subcloned fragments of the gab DNA identified the 53- to 55- and 45- to 48-kDa bands as products of the BamHI-SalI fragment and the 40- to 43-kDa band as the product of the EcoRI-SalI fragment. An additional 26- to 28-kDa band was identified as the product of the BamHI-HindIII fragment. Furthermore, the BamHI SalI fragment was shown to specify synthesis of the two GABA enzymes, whereas synthesis of the GABA carrier was specified by the BamHI-HindIII fragment. No catalytic function in addition to its regulatory role could be attributed to the EcoRI-SalI gene product. PMID- 2188955 TI - Cytosine methylation enhances Z-DNA formation in vivo. AB - The influence of cytosine methylation on the supercoil-stabilized B-Z equilibrium in Escherichia coli was analyzed by two independent assays. Both the M.EcoRI inhibition assay and the linking-number assay have been used previously to establish that dC-dG segments of sufficient lengths can exist as left-handed helices in vivo. A series of dC-dG plasmid inserts with Z-form potential, ranging in length from 14 to 74 base pairs, was investigated. Complete methylation of cytosine at all HhaI sites, including the inserts, was obtained by coexpression of the HhaI methyltransferase (M.HhaI) in cells also carrying a dC-dG-containing plasmid. Both assays showed that for all lengths of dC-dG inserts, the relative amounts of B and Z helices were shifted to more Z-DNA in the presence of M.HhaI than in the absence of M.HhaI. These results indicate that cytosine methylation enhances the formation of Z-DNA helices at the superhelix density present in E. coli. The B-Z equilibrium, in combination with site-specific base methylation, may constitute a concerted mechanism for the modulation of DNA topology and DNA protein interactions. PMID- 2188956 TI - Molecular cloning and characterization of an Erwinia carotovora subsp. carotovora pectin lyase gene that responds to DNA-damaging agents. AB - recA-mediated production of pectin lyase (PNL) and the bacteriocin carotovoricin occurs in Erwinia carotovora subsp. carotovora 71 when this organism is subjected to agents that damage or inhibit the synthesis of DNA. The structural gene pnlA was isolated from a strain 71 cosmid gene library following mobilization of the cosmids into a moderate PNL producer, strain 193. The cosmid complemented pnl::Tn5 but not ctv::Tn5 mutations. A constitutive level of PNL activity was detected in RecA+ and RecA- Escherichia coli strains carrying the pnlA+ gene on the high-copy-number plasmid pBluescript SK-. Mappings of Mu dI1734 (Km lac'ZYA) insertions in pnlA and unidirectional deletion analyses allowed localization of the gene to approximately 1.4 kilobases of DNA. A typical pnlA-lacZ transcriptional fusion was inducible in a RecA+ but not a RecA- derivative of strain 71. In contrast, the pnlA-lacZ fusion was not inducible in a RecA+ E. coli strain. DNA sequences homologous to pnlA were detected in E. carotovora subsp. carotovora and E. carotovora subsp. atroseptica strains and in one of four Erwinia rhapontici strains but not in Erwinia chrysanthemi. PMID- 2188958 TI - Sulfate and thiosulfate transport in Escherichia coli K-12: nucleotide sequence and expression of the cysTWAM gene cluster. AB - The nucleotide sequence of the sulfate and thiosulfate transport gene cluster has been determined and located 3' to the gene (cysP) encoding the thiosulfate binding protein. Four open reading frames, designated cysT, cysW, cysA, and cysM, have been identified. Similarities in primary structure were observed between (i) the deduced amino acid sequences of CysT and CysW with membrane-bound components of other binding protein-dependent transport systems, (ii) that of the CysA sequence with the "conserved" component of such systems, and (iii) that of the CysM sequence with O-acetylserine sulfhydrylase A (cysK gene product) and the beta-subunit of tryptophan synthase (coded by trpB). Expression of the four genes was analyzed in the T7 promoter-polymerase system. PMID- 2188957 TI - Sequence and structural characteristics of the trypsin-resistant T6 surface protein of group A streptococci. AB - The gene for the trypsin-resistant surface T6 protein of Streptococcus pyogenes D471 (M type 6) was cloned and expressed in Escherichia coli. The complete nucleotide sequence of the gene (tee6) and its flanking regions was determined and found to include only one major open reading frame coding for a protein of 537 amino acids (Mr, 57,675). The N terminus of the deduced protein sequence exhibits features of a typical signal sequence, and the C-terminal segment was found to have a high degree of homology with the membrane anchor region of other gram-positive surface proteins, such as streptococcal M protein, wapA protein from Streptococcus mutans and staphylococcal protein A. A hexapeptide having the consensus sequence LPSTGE and located immediately upstream of the C-terminal hydrophobic segment showed the highest degree of conservation at both the protein and DNA levels, with nearly all reported surface proteins from gram-positive cocci. The amino acid composition of the T6 protein revealed 21% serine and threonine residues distributed nearly regularly throughout the molecule, and analysis of the secondary structure predicted a conformation composed of greater than 70% beta-sheet potential interrupted by beta-turns or random coils. Localization experiments in E. coli show very little T6 protein in the periplasmic space. When found here, however, this T6 protein had a molecular mass of 55 kilodaltons, similar to that extracted from the streptococci by nonionic detergent. Most of the T6 protein was found localized in the membrane fraction, where it was composed of a triple band of 60, 58, and 57 kilodaltons. The coexistence of streptococcal surface proteins which are either resistant (T protein) or sensitive (M protein) to proteolytic enzymes may offer a new dimension to the modulation of these antigens under specific biological conditions. PMID- 2188959 TI - Sulfate and thiosulfate transport in Escherichia coli K-12: identification of a gene encoding a novel protein involved in thiosulfate binding. AB - The sequence of 1,973 nucleotides encompassing the region at and directly adjacent to the CysB-dependent promoter controlling expression and synthesis of the sulfate-thiosulfate transport system of Escherichia coli has been determined. The transcription start site has been mapped by primer extension. One open reading frame representing the first gene of the presumed sulfate transport operon was identified and designated cysP. The deduced amino acid sequence of the CysP polypeptide indicates the presence of a signal peptide. Expression of the cysP gene in the T7 promoter-polymerase system revealed the location of the gene product in the periplasm. Construction of a cysP insertional mutant and assays of binding and uptake of sulfate and thiosulfate by this mutant allowed the identification of the cysP gene product as a thiosulfate-binding protein. The TGA termination codon of cysP was found to overlap the putative ATG initiation codon of the next open reading frame, inferred as being essential for the sulfate transport system, and it was designated cysT. Preliminary sequence data from the corresponding region of the Salmonella typhimurium chromosome showed strictly homologous counterparts of the E. coli cysP and cysT genes. PMID- 2188960 TI - Mutations that affect control of the methylesterase activity of CheB, a component of the chemotaxis adaptation system in Escherichia coli. AB - Sensory adaptation by the chemotaxis system of Escherichia coli requires adjustments of the extent of methyl esterification of the chemotaxis receptor proteins. One mechanism utilized by E. coli to make such adjustments is to control the activity of CheB, the enzyme responsible for removing receptor methyl ester groups. Previous work has established the existence of a multicomponent signal transduction pathway that enables the chemotaxis receptor proteins to control the methylesterase activity in response to chemotactic stimuli. We isolated and characterized CheB mutants that do not respond normally to this control mechanism. In intact cells these CheB variants could not be activated in response to negative chemotaxis stimuli. Further characterization indicated that these CheB variants could not be phosphorylated by the chemotaxis protein kinase CheA. Disruption of the mechanism responsible for regulating methylesterase activity was also observed in cells carrying chromosomal deletions of either cheA or cheW as well as in cells expressing mutant versions of CheA that lacked kinase activity. These results provide further support for recent proposals that activation of the methylesterase activity of CheB involves phosphorylation of CheB by CheA. Furthermore, our findings suggest that CheW plays an essential role in enabling the chemotaxis receptor proteins to control the methylesterase activity, possibly by controlling the CheA-CheB phosphotransfer reaction. PMID- 2188962 TI - Cloning and sequence analysis of tryptophan synthetase genes of an extreme thermophile, Thermus thermophilus HB27: plasmid transfer from replica-plated Escherichia coli recombinant colonies to competent T. thermophilus cells. AB - Tryptophan synthetase genes (trpBA) of the extreme thermophile Thermus thermophilus HB27 were cloned by a novel method of direct plasmid transfer from replica-plated Escherichia coli recombinant colonies to competent T. thermophilus HB27 trpB cells. The nucleotide sequences of the trpBA genes were determined. The amino acid sequences deduced from the nucleotide sequences of Thermus trpB and trpA were found to have identities of 54.8 and 28.7%, respectively, with those of E. coli trpB and trpA genes. Low cysteine content (one in trpB; zero in trpA) is a striking feature of these proteins, which may contribute to their thermostability. PMID- 2188961 TI - Further electron microscopic studies on the expression of Escherichia coli group II capsules. AB - The de novo expression of Escherichia coli K1, K5, and K12 capsules was analyzed with immunoelectron microscopy in temperature upshift experiments, with upshift from 18 degrees C (capsule restrictive) to 37 degrees C (capsule permissive). Newly produced capsular polysaccharides appeared at the cell surface atop membrane adhesion sites (Bayer's junctions). After plasmolysis of the bacteria at an early expression stage, the capsular polysaccharides were labeled at discrete sites in the periplasm by the immunogold technique. After temperature upshift in the presence of carbonyl cyanide m-chlorophenylhydrazone (CCCP) or chloramphenicol, the polysaccharides were labeled in the cytoplasm. PMID- 2188963 TI - Rule governing the division pattern in Escherichia coli minB and wild-type filaments. AB - Escherichia coli minB mutants form anucleate minicells and multinucleate filaments. We show here that the overwhelming majority of nucleate cells contain 2n (n = 0, 1, 2, ...) nucleoids, as determined by 4',6-diamidino-2-phenylindole staining, and 2n (n = 1, 2, 3, ...) copies of the replication origin, as determined by flow cytometry. This shows that division sites are not chosen randomly among the available sites in minB filaments. Similarly, wild-type cells contain 2n nucleoids, both during cell division inhibition and when furazlocillin induced filaments are allowed to divide. We conclude that the min+ function is only to prevent septation only at polar sites; the placement of internal cell division sites must obey strict rules, which are the same in minB and wild-type cells. PMID- 2188964 TI - Amino-terminal deletions define a glutamine amide transfer domain in glutamine phosphoribosylpyrophosphate amidotransferase and other PurF-type amidotransferases. AB - A series of deletions was constructed in cloned Escherichia coli purF encoding glutamine phosphoribosylpyrophosphate amidotransferase. These deletions extended into the NH2 terminus of the protein and removed amino acids that are required for glutamine-dependent enzyme activity. Enzyme function, ascribed to the NH3 dependent activity, was retained in deletions that removed up to 237 amino acids. This result supports a model in which PurF-type amidotransferases contain an NH2 terminal glutamine amide transfer domain of approximately 194 to 200 amino acids fused to an aminator domain with NH3-dependent function. PMID- 2188965 TI - Characterization of biological ice nuclei from a lichen. AB - Biological ice nuclei (active at approximately -4 degrees C) were extracted from cells of the lichen Rhizoplaca chrysoleuca by sonication. Sensitivity to proteases, guanidine hydrochloride, and urea showed these nuclei to be proteinaceous. The nuclei were relatively heat stable, active from pH 1.5 to 12, and active without lipids, thereby demonstrating significant differences from bacterial ice nuclei. PMID- 2188966 TI - A family of genes encode the multiple forms of the Saccharomyces cerevisiae ribosomal proteins equivalent to the Escherichia coli L12 protein and a single form of the L10-equivalent ribosomal protein. PMID- 2188967 TI - Structure-function relationships in dihydrolipoamide acyltransferases. PMID- 2188968 TI - Accurate initiation by RNA polymerase II in a whole cell extract from Saccharomyces cerevisiae. AB - We have developed a simple procedure for isolating a transcriptional extract from whole yeast cells which obviates the requirement for nuclear isolation. Detection of accurate mRNA initiation by RNA polymerase II in the extract requires the use of a sensitive assay, recently described by Kornberg and co-workers (Lue, N. F., Flanagan, P. M., Sugimoto, K., and Kornberg, R. D. (1989) Science 246, 661-664) that involves activation by a GAL4-VP16 fusion protein and a template lacking guanosine residues in the coding strand. The extract is prepared from fresh or frozen yeast cells by disruption with glass beads and fractionation of proteins by ammonium sulfate precipitation. The alpha-amanitin-sensitive transcripts synthesized in the assay were identical to those produced in a parallel assay using a yeast nuclear extract. The activity of the whole cell extract is lower per mg of protein than a nuclear extract but proportional to the volume of the nucleus relative to the whole cell. The optimal ranges for several reaction components including template, mono- and divalent cations, and nucleotide substrate concentration were determined. Under optimal conditions the whole cell extract produced a maximum of approximately 1 X 10(-2) transcripts/template molecule in 30 min. PMID- 2188969 TI - Kinetic evidence for the formation of D-alanyl phosphate in the mechanism of D alanyl-D-alanine ligase. AB - The steady state kinetic mechanism, molecular isotope exchange and the positional isotope exchange (PIX) reactions of D-alanyl-D-alanine ligase from Salmonella typhimurium have been studied. The kinetic mechanism has been determined to be ordered Ter-Ter from initial velocity and product inhibition experiments. The first substrate to bind is ATP followed by the addition of 2 mol of D-alanine. Pi is released, and then D-alanyl-D-alanine and ADP dissociate from the enzyme surface. In the reverse direction D-alanyl-D-alanine exhibits complete substrate inhibition (Ki = 1.15 +/- 0.05 mM) by binding to the enzyme-ATP complex. In the presence of D-alanine, D-alanyl-D-alanine ligase catalyzed the positional exchange of the beta,gamma-bridge oxygen in [gamma-18O4]ATP to a beta-nonbridge position. Two possible alternate dead-end substrate analogs, D-2-chloropropionic acid and isobutyric acid, did not induce a positional isotope exchange in [gamma 18O4]ATP. The positional isotope exchange rate is diminished relative to the net substrate turnover as the concentration of D-alanine is increased. This is consistent with the ordered Ter-Ter mechanism as determined by the steady state kinetic experiments. The ratio of the positional isotope exchange rate relative to the net chemical turnover of substrate (Vex/Vchem) approaches a value of 1.4 as the concentration of D-alanine becomes very small. This ratio is 100 times larger than the ratio of the maximal reverse and forward chemical reaction velocities (V2/V1). This situation is only possible when the reaction mechanism proceeds in two distinct steps and the first step is much faster than the second step. The enzyme was also found to catalyze the molecular isotope exchange of radiolabeled D-alanine with D-alanyl-D-alanine in the presence of phosphate. These results are consistent with the formation of D-alanyl phosphate as a kinetically competent intermediate. PMID- 2188970 TI - Regulation of alpha 1 (I)-collagen gene expression in response to cell adhesion in Swiss 3T3 fibroblasts. AB - Nonadhesive conditions cause Swiss 3T3 fibroblasts to enter a quiescent state that is reversed upon reattachment to a surface. Previously, we demonstrated that adhesion in serum-free conditions is sufficient to activate suspension-arrested cells out of Go, with the induction of the growth-associated genes, c-fos, c-myc, and actin. In this study, we have employed this system to identify programs of gene expression that respond primarily to the adhesive state of the cell, rather than the growth state. We show that cells in different adhesive states can be distinguished by their patterns of protein synthesis. Analysis of one adhesion responsive protein led to its identification as pro-alpha 1 (I)-collagen. Pro alpha 1 (I)-collagen synthesis and mRNA levels are decreased up to 6-fold in suspension-arrested fibroblasts, but are enhanced up to 5-fold as cells approach confluence. This suggests that the reduced expression in suspension-arrested cells is not simply a result of quiescence. In addition, reattachment of suspended cells in serum-free conditions caused a 7-fold induction of collagen mRNA levels and a greater than 20-fold rise in the rate of procollagen synthesis. The expression of c-myc was induced during adhesion in serum-free medium as well as by serum addition to suspension-arrested cells. However, alpha 1 (I)-collagen gene expression was unaffected by serum in the absence of adhesion. These results indicate that collagen gene expression is directly responsive to cell adhesion, independent of the growth state. PMID- 2188971 TI - Kinetic evidence of a rapid activation of phosphatidylcholine hydrolysis by Ki ras oncogene. Possible involvement in late steps of the mitogenic cascade. AB - A novel phospholipase C specific for phosphatidylcholine has been shown to be activated by several agonists. Also, recent evidence suggests that transformation mediated by the ras oncogene possibly involves the activation of this novel phospholipid degradative pathway which would account for the increased diacylglycerol levels associated with transformation. Here we use a mutant of Ki ras which is temperature-sensitive for transformation to investigate the kinetics of activation of the phosphodiesterase-mediated turnover of phosphatidylcholine. Upon shift to the permissive temperature, products of the activated phosphatidylcholine-specific phospholipase C were detected by 30 min and reached maximal levels by 1-2 h. These results suggest that the product of the ras oncogene rapidly activates the phosphodiesteratic hydrolysis of phosphatidylcholine. Furthermore, the fact that at least 4 h are required for serum to activate this phospholipase C strongly suggests that the ras oncogene product might be involved in late steps of the mitogenic signaling cascade. PMID- 2188972 TI - Assembly and disassembly of RecA protein filaments occur at opposite filament ends. Relationship to DNA strand exchange. AB - RecA protein primarily associates with and dissociates from opposite ends of nucleoprotein filaments formed on linear duplex DNA. RecA nucleoprotein filaments that are hydrolyzing ATP therefore engage in a dynamic process under some conditions that has some of the properties of treadmilling. We have also investigated whether the net polymerization of recA protein at one end of the filament and/or a net depolymerization at the other end drives unidirectional strand exchange. There is no demonstrable correlation between recA protein association/dissociation and the strand exchange reaction. RecA protein-mediated DNA strand exchange is affected minimally by changes in reaction conditions (dilution, pH shift, or addition of small amounts of adenosine-5'-O-(3 thiotriphosphate) that have large and demonstrable effects on recA protein association, dissociation, or both. Rather than driving strand exchange, these assembly and disassembly processes may simply represent the mechanism by which recA nucleoprotein filaments are recycled in the cell. PMID- 2188973 TI - Protein disulfide-isomerase is a substrate for thioredoxin reductase and has thioredoxin-like activity. AB - We have demonstrated that calf liver protein disulfide-isomerase (Mr 57,000) is a substrate for calf thymus thioredoxin reductase and catalyzes NADPH-dependent insulin disulfide reduction. This reaction can be used as a simple assay for protein disulfide-isomerase during purification in place of the classical method of reactivation of incorrectly oxidized ribonuclease A. Protein disulfide isomerase contains two redox-active disulfides/molecule which were reduced by NADPH and calf thioredoxin reductase (Km approximately 35 microM). The isomerase was a poor substrate for NADPH and Escherichia coli thioredoxin reductase, but the addition of E. coli thioredoxin resulted in rapid reduction of two disulfides/molecule. Tryptophan fluorescence spectra were shown to monitor the redox state of protein disulfide-isomerase. Fluorescence measurements demonstrated that thioredoxin--(SH)2 reduced the disulfides of the isomerase and allowed the kinetics of the reaction to be followed; the reaction was also catalyzed by calf thioredoxin reductase. Equilibrium measurements showed that the apparent redox potential of the active site disulfide/dithiols of the thioredoxin domains of protein disulfide-isomerase was about 30 mV higher than the disulfide/dithiol of E. coli thioredoxin. Consistent with this, experiments using dithiothreitol or NADPH and thioredoxin reductase-dependent reduction and precipitation of insulin demonstrated differences between protein disulfide isomerase and thioredoxin, thioredoxin being a better disulfide reductase but less efficient isomerase. Protein disulfide-isomerase is thus a high molecular weight member of the thioredoxin system, able to interact with both mammalian NADPH-thioredoxin reductase and reduced thioredoxin. This may be important for nascent protein disulfide formation and other thiol-dependent redox reactions in cells. PMID- 2188974 TI - Copper uptake in wild type and copper metallothionein-deficient Saccharomyces cerevisiae. Kinetics and mechanism. AB - The mechanism of copper uptake in Saccharomyces cerevisiae has been investigated using a combination of 64Cu2+ and atomic absorption spectrophotometry. A wild type copper-resistant CUP 1R-containing strain and a strain carrying a deletion of the CUP1 locus (yeast copper metallothionein) exhibited quantitatively similar saturable energy-dependent 64Cu2+ uptake when cultures were pregrown in copper free media (medium [Cu] approximately 15 nM). The kinetic constants for uptake by the wild type strain were Vmax = 0.21 nmol of copper/min/mg of protein and Km = 4.4 microM. This accumulation of 64Cu2+ represented net uptake as confirmed by atomic absorption spectrophotometry. This uptake was not seen in glucose-starved cells, but was supported in glycerol- and ethanol-grown ones. Uptake was inhibited by both N3- and dinitrophenol and was barely detectable in cultures at 4 degrees C. When present at 50 microM, Zn2+ and Ni2+ inhibited by 50% indicating that this uptake process was relatively selective for Cu2+. 64Cu2+ accumulation was qualitatively and quantitatively different in cultures either grown in or preincubated with cold Cu2+. Either treatment resulted in the appearance of a fast phase (t 1/2 approximately 1 min) of 64Cu2+ accumulation which represented isotopic exchange since it did not lead to an increase in the mass of cell associated copper; also, it was not energy-dependent. Exchange of 64Cu2+ into this pool was not inhibited by Zn2+. Pretreatment with Cu2+ caused a change in the rate of net accumulation as well; a 3-h incubation of cells in 5 microM medium Cu2+ caused a 1.6-fold increase in the velocity of energy-dependent uptake. Prior addition of cycloheximide abolished this Cu2(+)-dependent increase and, in fact, inhibited the 64Cu2+ uptake velocity by greater than 85%. The exchangeable pool was also absent in cycloheximide, Cu2(+)-treated cells suggesting that exchangeable Cu2+ derived from the copper taken up initially by the energy-dependent process. The thionein deletion mutant was similar to wild type in response to medium Cu2+ and cycloheximide indicating that copper metallothionein is not directly involved in Cu2+ uptake (as distinct from retention) in yeast. PMID- 2188975 TI - Purification and characterization of urease from Helicobacter pylori. AB - Urease was purified 112-fold to homogeneity from the microaerophilic human gastric bacterium, Helicobacter pylori. The urease isolation procedure included a water extraction step, size exclusion chromatography, and anion exchange chromatography. The purified enzyme exhibited a Km of 0.3 +/- 0.1 mM and a Vmax of 1,100 +/- 200 mumols of urea hydrolyzed/min/mg of protein at 22 degrees C in 31 mM Tris-HCl, pH 8.0. The isoelectric point was 5.99 +/- 0.03. Molecular mass estimated for the native enzyme was 380,000 +/- 30,000 daltons, whereas subunit values of 62,000 +/- 2,000 and 30,000 +/- 1,000 were determined. The partial amino-terminal sequence (17 residues) of the large subunit of H. pylori urease (Mr = 62,000) was 76% homologous with an internal sequence of the homohexameric jack bean urease subunit (Mr = 90,770; Takashima, K., Suga, T., and Mamiya, G. (1988) Eur. J. Biochem. 175, 151-165) and was 65% homologous with amino-terminal sequences of the large subunits of heteropolymeric ureases from Proteus mirabilis (Mr = 73,000) and from Klebsiella aerogenes (Mr = 72,000; Mobley, H. L. T., and Hausinger, R. P. (1989) Microbiol. Rev. 53, 85-108). The amino-terminal sequence (20 residues) of the small subunit of H. pylori urease (Mr = 30,000) was 65 and 60% homologous with the amino-terminal sequences of the subunit of jack bean urease and with the Mr = 11,000 subunit of P. mirabilis urease (Jones, B. D., and Mobley, H. L. T. (1989) J. Bacteriol. 171, 6414-6422), respectively. Thus, the urease of H. pylori shows similarities to ureases found in plants and other bacteria. When used as antigens in an enzyme-linked immunosorbent assay, neither purified urease nor an Mr = 54,000 protein that co-purified with urease by size exclusion chromatography was as effective as crude preparations of H. pylori proteins at distinguishing sera from persons known either to be infected with H. pylori or not. PMID- 2188976 TI - Characterization of a human apolipoprotein E gene enhancer element and its associated protein factors. AB - An enhancer element in the 5' flanking region of the human apolipoprotein E gene, known as upstream regulatory element 1 (URE1), has previously been implicated in the expression of this gene. The URE1 element, which spans nucleotides -193 to 124 of the 5'-flanking region of the human apolipoprotein E gene, contains two sequences that bind to nuclear proteins, as determined by the DNase I footprinting assay. In the present study of URE1, we have characterized these sequences further. Deletion of one of the footprint sequences, at nucleotides 161 to -141, reduced URE1 enhancer activity substantially. A 30-base pair oligonucleotide that included this protein-binding sequence was able, by itself, to act as an enhancer. This sequence, termed the positive element for transcription (PET), was demonstrated by gel retention analysis to bind at least two protein factors, one of which is the transcription factor Sp1. Sp1 appeared to be the only protein required for the enhancer activity of PET to be manifested. In vitro transcription assays showed that the PET sequence was necessary for efficient transcription directed by the apoE promoter and that the PET sequence was the dominant regulatory element in the apoE promoter. Gel filtration chromatography and PET oligonucleotide-affinity chromatography were used to isolate a second PET-binding factor, a Mr = 55,000 protein, from HeLa cell nuclear extracts. It appeared to compete with Sp1 for a common binding site in the PET sequence, but it was not required for enhancer activity. The second footprint sequence in URE1, at nucleotides -184 to -173, also bound Sp1, but it was not required for enhancer activity. A third Sp1-binding region was located at a proximal GC box element (nucleotides -54 to -45). This region had no enhancer activity, but it was required for maximum transcriptional activity of the apoE promoter. Thus, the regulation of apoE gene expression is influenced by different protein-binding sequences, with transcription factor Sp1 playing major roles in both basal promoter activity and enhancer activity. PMID- 2188977 TI - Replacement of the human insulin receptor transmembrane and cytoplasmic domains by corresponding domains of the oncogene product v-ros leads to accelerated internalization, degradation, and down-regulation. AB - Internalization, degradation, and insulin-induced down-regulation of insulin receptors were studied comparatively in transformed Chinese hamster ovary (CHO) cell lines, CHO.T and CHO.IR.ros, respectively expressing either the wild-type human insulin receptor (hIR) or a mutated hybrid receptor in which the transmembrane and cytoplasmic domains of hIR were replaced by corresponding domains of the transforming protein p68gag-ros (v-ros) of avian sarcoma virus UR2. At 37 degrees C, degradation of insulin receptors photoaffinity labeled on the cell surface (440 kDa) was most rapid for the hybrid hIR.ros (t1/2 1.0 +/- 0.1 h), intermediate for the wild-type hIR (t1/2 2.7 +/- 0.5 h), and slowest for the endogenous CHO insulin receptors (t1/2 3.7 +/- 0.7 h). Initial intracellular accumulation of the hIR.ros hybrid was also most rapid, reaching maximal amounts in 20 min following which the receptors disappeared rapidly from the intracellular compartment. In contrast, intracellular accumulation of the receptors in the CHO.T and CHO cells was slower, reaching maximal amounts in 60 min, and rapid disappearance of the receptors from the intracellular compartment did not occur. Chloroquine, a lysosomotropic agent, inhibited degradation of both the wild-type hIR and the chimeric hIR.ros and increased their intracellular accumulation. However, the chloroquine effect was much more marked for the hIR.ros receptors whose intracellular accumulation was increased by greater than 300% (in comparison with approximately 60% increase for the wild-type hIR), demonstrating marked intracellular degradation of the hybrid hIR.ros at chloroquine-sensitive sites. Insulin-induced down-regulation of the cell surface hIR.ros (52% loss in 3 h) was also more marked than the wild-type hIR (approximately 30% loss in 3 h). Thus, in the hybrid hIR.ros receptor, which was shown previously to exhibit insulin-stimulated autophosphorylation and kinase activity but not insulin-stimulated metabolic function, the capacity for internalization and down-regulation is not only preserved but is also markedly accelerated. These findings suggest that 1) the postreceptor coupling mechanisms mediating insulin-induced receptor internalization, degradation, and down regulation are different from those mediating metabolic functions; and 2) v-ros may contain the structural information directing accelerated receptor catabolism. PMID- 2188978 TI - Two subunits of the canine signal peptidase complex are homologous to yeast SEC11 protein. AB - Canine microsomal signal peptidase activity was previously isolated as a complex of five subunits (25, 22/23, 21, 18, and 12 kDa). Two of the signal peptidase complex (SPC) subunits (23/23 and 21 kDa) have been cloned and sequenced. One of these, the 21-kDa subunit, was observed to be a mammalian homolog of SEC11 protein (Sec11p) (Greenburg, G., Shelness, G. S., and Blobel, G. (1989) J. Biol. Chem. 264, 15762-15765) a gene product essential for signal peptide processing and cell growth in yeast (Bohni, P.C., Deshqies, R.J., and Schekman, R.W. (1988) J. Cell Biol. 106, 1035-1042). cDNA clones for the 18-kDa SPC subunit have now been characterized and found to encode a second SEC11p homolog. Both the 18- and 21-kDa canine SPC subunits are integral membrane proteins by virtue of their resistance to alkaline extraction. Upon detergent solubilization, both proteins are found in a complex with the 22/23 kDa SPC subunit, the only SPC subunit containing N-linked oligosaccharide. No steady-state pool of canine Sec11p-like monomers is detected in microsomal membranes. Alkaline extraction of microsomes prior to solubilization or solubilization at alkaline pH causes partial dissociation of the SPC. The Sec11p-like subunits displaced from the complex under these conditions demonstrate no signal peptide processing activity by themselves. The existence of homologous subunits is common to a number of known protein complexes and provides further evidence that the association between SPC proteins observed in vitro may be physiologically relevant to the mechanism of signal peptide processing and perhaps protein translocation. PMID- 2188979 TI - cDNA cloning and chromosomal assignment of the human O6-methylguanine-DNA methyltransferase. cDNA expression in Escherichia coli and gene expression in human cells. AB - The O6-methylguanine-DNA methyltransferases are the most common form of cellular defense against the biological effects of O6-methylguanine in DNA. By screening a cDNA library with oligonucleotide probes derived from the active site amino acid sequence of the bovine methyltransferase, we have isolated a cDNA clone for the human enzyme. The cDNA contains a single open reading frame encoding a protein of Mr 21,700 which exhibits considerable homology to three bacterial methyltransferases. When provided with an Escherichia coli lac promoter, the encoded polypeptide can be expressed in E. coli to produce an active methyltransferase which is indistinguishable in size from the protein from human cells. The enzyme expressed in this way is functional in vivo and protects an E. coli methyltransferase deletion mutant against the mutational and cytotoxic properties of the alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine. The methyltransferase gene spans at least 15 kilobases and is located on human chromosome 10. Alkylating agent-resistant Mex+ cells which express the methyltransferase protein contain a methyltransferase mRNA of about 1 kilobase. However, this mRNA is absent from three alkylation sensitive Mex- human cell lines indicating that the regulation of methyltransferase gene expression in these cell lines may be transcriptional. PMID- 2188980 TI - Purification and characterization of recombinant plasminogen activator inhibitor 1 from Escherichia coli. AB - A recombinant form of plasminogen activator inhibitor-1 (rPAI-1) has been purified from lysates of pCE1200, a bacterial expression vector containing the full length PAI-1 gene, by utilizing sequential anion exchange and cation exchange chromatography on Q-Sepharose and S-Sepharose columns. Approximately 140 mg of rPAI-1, estimated at 98% purity on the basis of analytical high performance liquid chromatography, could be obtained from 200 g wet weight of cells. The purified protein exhibited a single Coomassie Blue-stainable band at the region of Mr = 42,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and an NH2-terminal amino acid sequence consistent with the expected translation product of the pCE1200 PAI-1 insert. The rPAI-1 rapidly inhibited single- and two chain tissue plasminogen activators, as well as urokinase, with apparent second order rate constants in the range of 2-5 x 10(7) M-1 s-1. A specific activity measurement of 250,000 units/mg was calculated for the rPAI-1 based on its ability to inhibit the enzymatic activity of a single-chain tissue plasminogen activator. Stability studies showed that the activity of the rPAI-1 was very stable when stored at temperatures of 25 degrees C or lower, but decayed within hours when stored at 37 degrees C. Sodium dodecyl sulfate treatment, which partially activates the latent form of natural PAI-1, inactivated rPAI-1. These results show that the purified rPAI-1 produced from pCE1200 displays many of the properties associated with the biologically active form of natural PAI-1. PMID- 2188981 TI - Aplasia of the submandibular gland. A case report. AB - A 34-year-old Japanese male had pain radiating from his right mandibular body to the temporal region. Computerized tomography was undertaken to examine his cerebral status. It eventually revealed the absence of the right submandibular gland, although the left submandibular gland was present. The corresponding space was occupied by a lymph node. Furthermore, sialography showed the existence of Wharton's duct only. The literature on this rare occurrence is reviewed and the significance to the patient discussed. PMID- 2188982 TI - An ancient "tumour" from pre-Columbian Chile. AB - A case of an expansile facial lesion discovered in the more than 600 years old skeletal remains of a 22-25-year-old female is discussed. Gross, radiographic and histological studies were accomplished on the specimen. Although a definitive diagnosis could not be derived because of the age and condition of the specimen, differential diagnoses are discussed and a probable diagnosis rendered. PMID- 2188983 TI - Rationale of feeding systems for lactating dairy cows. AB - Manipulations of the lactation cycle are achieved through nutritional regimens and generally result in a restriction of the physiological lactation cycle. Most models of lactation used in management programmes only describe the average time course of lactation for groups of cows on a given feeding regimen. This is inadequate for the variety of feeding systems in use on British farms. In the present paper several existing models of lactation have been critically evaluated. An integral equation approach has been developed to rationalize experimental observations and currently accepted biological concepts. PMID- 2188984 TI - A review of metabolism of labeled glucoses for use in measuring glucose recycling. AB - The fate of tritium from each carbon of D-glucose and the metabolism of L-glucose and 2-deoxy-D-glucose are known. Differences in metabolism of labeled glucoses can be used to quantify physical and chemical recycling of glucose. Only physical recycling is measured by [1-3H]-L-glucose, whereas [U-14C]-D-glucose measures total recycling. The difference between [1-3H]-L-glucose and [U-14C]-D-glucose, therefore, is chemical recycling. Recycling from extracellular binding sites and hepatic glucose 6-phosphate can be measured by difference between [1,2-3H]-2 deoxy-D-glucose and [1-3H]-L-glucose, and the difference in irreversible loss of the two will measure extrahepatic uptake of D-glucose. Recycling via Cori-alanine cycle plus CO2 is the difference in irreversible loss measured by using [6-3H] glucose and [U-14C]-D-glucose. Recycling via the hexose monophosphate pathway can be determined by difference in irreversible loss between [1-3H]-D-glucose and [6 3H]-D-glucose. Recycling via CO2 and glycerol must be measured directly with [U 14C]glucose, bicarbonate, and glycerol. Recycling via hepatic glycogen can be estimated by subtracting all other measured chemical recycling from total chemical recycling. This review describes means to quantify glucose recycling in vivo, enabling studies of mechanisms for conservation and utilization of glucose. PMID- 2188985 TI - Early ambulation after 5 French diagnostic cardiac catheterization: results of a multicenter trial. AB - Because earlier ambulation and discharge after cardiac catheterization may result in the increased utilization of outpatient facilities, a prospective five center clinical pilot trial assessing the safety and outcome of early ambulation after routine left heart catheterization was performed in 287 patients. Catheterization routines at each clinical center were unchanged throughout the study. After the diagnostic catheterization using 5 French (F), preformed, large lumen catheters and arterial puncture compression (mean 15 min, range 5 to 52), 260 patients were ambulated by a physician at a mean time of 2.6 h (range 1.8 to 3.1) after catheterization. Follow-up examination or a phone call 24 to 72 h later was performed to assess late results. The mean age of the patients was 58 years (range 25 to 91); 166 (58%) were men. Left ventricular ejection fraction was 54 +/- 15%. One hundred twenty-seven patients (44%) received intravenous heparin (1,500 to 5,000 U as an intravenous bolus) and 136 (47%) received aspirin. Major complications included transient ischemic attack (one patient) and ventricular tachycardia requiring cardioversion during ventriculography (two patients). A small hematoma (less than 5.0 cm) after ambulation occurred early (from compression to standing) in 14 patients (5%; 9 received heparin, 8 were taking aspirin) and later (after standing to 72 h) in 9 patients (3%; 2 receiving heparin, 2 taking aspirin). Five patients with a hematoma had studies with a 6F sheath. No patient required surgical intervention for early or late hematoma. Only three patients (1%) needed a 7F or 8F catheter because of suboptimal 5F coronary angiography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188986 TI - Novel organ-specific circulating cardiac autoantibodies in dilated cardiomyopathy. AB - To determine whether organ-specific cardiac autoantibodies are present in dilated cardiomyopathy, indirect immunofluorescence on human heart and skeletal muscle was used to test sera from 200 normal subjects and from 65 patients with dilated cardiomyopathy, 41 with chronic heart failure due to myocardial infarction and 208 with other cardiac disease. Three immunofluorescence patterns were observed: diffuse cytoplasmic on cardiac tissue only (organ-specific), fine striational on cardiac and, to a lesser extent, skeletal muscle (cross-reactive 1) and broad striational on both cardiac and skeletal muscle (cross-reactive 2). Cardiac specificity of the cytoplasmic pattern was confirmed by absorption studies with homogenates of human atrium, skeletal muscle and rat liver. Organ-specific cardiac antibodies (IgG; titer range 1/10 to 1/80) were more frequent in patients with dilated cardiomyopathy (17 [26%] of 65) than in those with other cardiac disease (2 [1%] of 208, p less than 0.0001) or heart failure (0 [0%] of 41, p less than 0.001) or in normal subjects (7 [3.5%] of 200, p less than 0.0001). Organ-specific cardiac antibodies were more common in patients with dilated cardiomyopathy and in those with fewer symptoms (8 of 15 in New York Heart Association functional class I versus 9 of 50 in classes II to IV, p less than 0.01) and more recent (less than 2 years) onset of disease (9 of 19 versus 8 of 46, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188987 TI - Transluminal atherectomy for occlusive peripheral vascular disease. AB - The failure of balloon angioplasty to provide a durable result has led to the development of other methods of catheter-associated interventional therapy. In this study, 112 patients with superficial femoral artery stenosis or occlusion were treated with percutaneous atherectomy. Patients were considered to have a simple lesion if the occluded or stenotic arterial segment was less than 5 cm, and a complex lesion if the length of the occluded segment was greater than 5 cm. All atherectomies were performed in the superficial femoral and popliteal arteries; urokinase thrombolysis was used in conjunction with atherectomy in 16 patients. Atherectomy was considered successful if there was less than 20% residual stenosis determined by arteriography. Initial atherectomy results (30 day patency) were 100% successful in the group with a simple lesion and 93% successful in the group with a complex lesion. At a mean follow-up period of 12 months (range 5 to 24), there was a continued patency rate of 93% and 86%, respectively, in the simple and complex groups. In the patients who had restenosis, all pathologic specimens obtained during the second procedure demonstrated myointimal hyperplasia and organized thrombus. Eight major complications (7.1%) occurred, including one fatal myocardial infarction. The complication rate was 3.5% in the simple group and 8.3% in the complex group. With the exception of the myocardial infarction, all complications were associated with catheter entry site hematomas. Femoropopliteal atherectomy has a high rate of success and low morbidity and mortality for both simple and complex lesions and is a viable and competitive alternative therapy for patients with severe peripheral vascular disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188988 TI - Relative insensitivity of densitometric stenosis measurement to lumen edge determination. AB - Coronary artery stenosis measurement from coronary arteriograms is dependent on lumen edge determination. In theory, dependence may be minimized by densitometric integration of the entire lumen as compared with densitometric determination of edges alone coupled with calculation of lumen size by geometric formulas. To assess the impact of approximations of lumen border position when densitometric and geometric methods are employed, external, intermediate and internal borders were defined and used with each method to calculate lumen narrowing from images of contrast-filled, asymmetrically stenotic model vessels and from clinically generated coronary arteriograms. Actual cross-sectional area narrowing of models correlated almost perfectly with densitometric narrowing for each of the three border criteria (external: r = 0.99, n = 192; intermediate: r = 0.99, n = 192; internal: r = 0.99, n = 192). Lumen narrowing calculated by assuming a circular lumen geometry with a diameter equal to the distance between these identical borders correlated less well with true area narrowing (external: r = 0.79, n = 192; intermediate: r = 0.83, n = 192; internal: r = 0.78, n = 192); the residual variance of the densitometric regression was significantly less than that of the geometric regression for each of the three border criteria (external: 8.13 versus 372, p less than 0.001; intermediate: 7.39 versus 315, p less than 0.001; internal: 7.13 versus 531, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2188989 TI - Prospective detection by Doppler color flow imaging of additional defects in infants with a large ventricular septal defect. AB - The use of Doppler color flow imaging and axial contrast angiography in the preoperative detection of additional ventricular septal defects (in the setting of a known large defect) were compared in a prospective fashion. One hundred seventy-nine infants with two ventricles (each of at least normal size) and a large, nonrestrictive ventricular septal defect underwent reparative surgery before 2 years of age. The reference standard for the presence of additional defects was intraoperative verification or (in cases in which the surgeon did not visualize any additional defect) subsequent identification at postoperative angiography, postoperative color Doppler examination or reoperation. Only six patients (3%) had additional ventricular septal defects confirmed at the time of repair; an additional five (3%) had defects found only postoperatively. The negative predictive value of Doppler color flow imaging and angiography was 0.95 (168 of 176) and 0.97 (168 of 174), respectively. The sensitivity was 0.27 (3 of 11) and 0.45 (5 of 11), respectively. For certain malformations with a very low prevalence of additional muscular defects (such as perimembranous ventricular septal defect with normally aligned great arteries), a clinical trial of reparative surgery without prior invasive study appears reasonable. PMID- 2188990 TI - Color Doppler echocardiography, Fred Astaire and the magic of Hollywood. PMID- 2188991 TI - Syndromes of accelerated atherosclerosis: role of vascular injury and smooth muscle cell proliferation. AB - Vascular injury represents a critical initiating event in the pathogenesis of various vascular diseases, including atherosclerosis. This review discusses 1) the current understanding and a new pathologic classification of vascular injury; 2) the resultant cellular pathophysiologic responses, specifically, lipid accumulation, platelet aggregation, thrombus formation and smooth muscle cell proliferation; 3) the role of vascular injury in the pathogenesis of spontaneous and accelerated atherosclerosis; and 4) emerging therapeutic approaches in preventing these vascular diseases. The process of type I vascular injury (nondenuding functional injury) followed by lipid accumulation, monocyte and platelet adhesion, smooth muscle cell proliferation and resultant plaque formation represents the prevalent view of the early stages of spontaneous atherogenesis. The syndromes of accelerated atherosclerosis (namely, heart transplant atherosclerosis, coronary vein graft disease and restenosis after percutaneous transluminal coronary angioplasty) appear to share etiologic mechanisms with spontaneous atherosclerosis by means of the "response to injury" hypothesis. However, type II and type III vascular injury (denuding endothelial and intimal injury with or without medial damage) followed by thrombus and its organization by smooth muscle cell proliferation and subsequent fibrosis appear to be responsible for the vascular process. This accelerated and premature occlusive process accounts for significant morbidity and mortality in patients with these conditions. Better understanding of the nature of vascular injury and its pathophysiologic responses in these clinical situations may aid in developing therapeutic strategies for preventing these vascular diseases. PMID- 2188992 TI - Determination of dietary vitamin B-6 intake: is it accurate? PMID- 2188993 TI - Oligodeoxynucleoside phosphorothioate stability in subcellular extracts, culture media, sera and cerebrospinal fluid. AB - Degradation of a synthetic oligodeoxynucleoside phosphorothioate was studied in six systems used for antisense inhibition experiments. Oligodeoxynucleoside phosphorothioates were degraded very slowly at 37 degrees C in all of the systems studied. Measured half-lives of pentadecamers were 12 +/- 1 h in rabbit reticulocyte lysate, 7 +/- 1 h in HeLa cell postmitochondrial extract, 14 +/- 2 h in RPMI 1640 with 10% fetal bovine serum, 8 +/- 1 h in undiluted fetal bovine serum, 9 +/- 1 h in adult human serum, and 19 +/- 7 h in rat cerebrospinal fluid. PMID- 2188994 TI - [Epithelial cancer of the ovary. Contribution of the experiences of a treatment facility to the current data of prognosis and treatment]. AB - Results obtained by the authors and a review of the literature have made them able to point out recent developments in cases of epithelial cancer of the ovary diagnosed in an advanced stage of the disease. This is the most frequent finding when the diagnosis is made and it is most important in assessing the future prognosis to know how far on the disease has progressed. Cancer of the ovary has long been thought of as a peritoneal disease, but all the same 40% of metastases occur further away and the majority of these are in the pleura or the lung and more rarely in the brain; and all these have been observed. The degree of differentiation is another important element for prognosis. Deciding how differentiated tissue is, is relatively subjective. A scoring protocol is suggested to make the assessment more systematic. The grading can be varied according to the response to treatment. A great majority of authorities believe that reduction of the size of the tumour surgically should be the first procedure but how useful this is has never been proved because there has never been any controlled study. It is possible in most cases to reduce the size of the tumour greatly but often this may need removal of some of the intestines with acceptable morbidity. Chemotherapy with Cisplatin, Cyclophosphamide and in the hands of certain authors, Doxorubicine, has been shown to be helpful in 80% of cases and seems to be the most appropriate treatment. PMID- 2188995 TI - [Multiple-fetus pregnancies. I. Myths and reality]. AB - Pregnancies with many fetuses (triplets and more) have at all times been found interesting and unusual. Their rare and spectacular characteristics have for long been considered as divine punishment for the sin of adultery or bestiality or on the other hand as a mark of fertility and a gift from God. The authors report several legends (the Porcelets, the Trazegnies, la Dame de Montigny...) as well as the celebrated cases of fraud. Since techniques have been developed for medical handling of assisted reproduction, multiple pregnancies have become much more frequent. There is no case of survival of all fetuses when there have been more than six born at a time. PMID- 2188996 TI - [Giant uterine leiomyoma and pregnancy. Clinical, radiologic, unusual histopathologic aspects]. AB - The authors report a case of uterine leiomyomas diagnosed during the first trimester of pregnancy. The most unusual presentation of this observation did not allow any diagnosis through clinical exam, either by sonographic and X ray technics (magnetic resonance imaging, computer tomography) or by the classical histological study. The intra abdominal tumors compatible with imagery are argued: ovarian cyst, gelatinous disease of the peritoneum, desmoid tumor, lymphoma, lymphangiomyoma. The right diagnosis has been established as a last resort to immunocytochemistry. PMID- 2188997 TI - [Megabladder. Microcolon. Prenatal ultrasonic diagnosis and a review of the literature. Apropos of a case]. AB - The condition of "megacystis-microcolon" is a very rare condition which can now be diagnosed ante-natally due to ultrasound. The presence of a megacystis (large bladder) with increased levels of amniotic fluid makes it possible to eliminate other ante-natal causes of dilatation of the bladder and in particular when it is found in a female fetus (as it is in 80% of cases). At birth, one finds, apart from the massive dilatation of the bladder with very little effect on the upper urinary tract, a microcolon with complete absence of peristalsis. This last abnormality always leads to a catastrophic short term result because treatment is quite ineffective. Many histological studies have been carried out and these sometimes differ from one another but it is possible to think that the condition is due to pathology of neurogenic origin in the muscle of the bladder and the aetiology of this is unknown. Finally, because there have been a few familial cases, there may be a genetic element in this illness that has such a poor prognosis. PMID- 2188998 TI - [Late cerclage]. AB - Cervico-isthmial incompetence develops in the second trimester of pregnancy. There are problems as to the correct treatment. The authors report four cases where stitches were put in late using the technique of "parachute" cerclage. This made it possible for four live babies to be born. A search of the literature shows that after late cerclage in 60-90% of cases pregnancy continues normally. But it has to be realised that complications do occur and these are mainly chorio amnionitis which carries a bad prognosis obstetrically and also premature rupture of the membranes. The authors recommend this manoeuvre in spite of the risks because of the benefits that can be obtained. The procedure should only be carried out if there is no cervico-vaginal infection as determined by negative swabs and tocolytic treatment should also be given. PMID- 2188999 TI - Development of an AIDS vaccine. Biological and ethical challenges. AB - The biologic, ethical, and social obstacles in AIDS vaccine development are explored. Current understanding of the immunodeterminants of HIV-1 pathogenesis is reviewed and ideal biological properties for an AIDS vaccine are proposed. Options for clinical trial design, criteria for entry into clinical trials, and provision for care of volunteers who experience vaccine-associated adversity are discussed. PMID- 2189000 TI - Escherichia coli and Klebsiella vaccines and immunotherapy. AB - A polyvalent vaccine has been prepared from the capsular polysaccharide of 24 different serotypes of Klebsiella spp. Nearly 200 volunteers have received this vaccine. It is very well tolerated and elicits both binding (ELISA) and functional antibody to 21 of 24 antigens. Antibodies were also detected against 10 serotypes not included in the vaccine. An immunoglobulin for intravenous use (IVIG) was more protective in mouse lethality assays and enhanced opsonophagocytic killing of bacteria more than standard, nonhyperimmune globulin. A monovalent E. coli conjugate vaccine against O18ac antigen was safe and highly immunogenic in humans. A 12-valent conjugate vaccine elicits good levels of antibody in rabbits, and will soon undergo phase I testing in humans. These vaccines might best be used for inducing antibody in donor plasma that could be made into IVIG for passive administration. PMID- 2189001 TI - Malaria vaccines. AB - Malaria continues to be a major worldwide problem. Recent advances in our understanding of the parasite and the immune response to malarial infections has resulted in major advances in the progress toward an effective malaria vaccine. Owing to the complexity of the parasite's life cycle, an effective vaccine will most assuredly contain components selected to stimulate potent immune mechanisms directed at various points in the parasite's life cycle. Considering the increasing incidence of drug resistance, combined with the high case-fatality rate, most research efforts have focused on developing a vaccine against Plasmodium falciparum. A successful vaccine against P. falciparum would be a significant advance in medical science. One must not, however, forget the severe morbidity associated with the other three human malarial species. As information is gained in the effort against P. falciparum, it is rapidly incorporated into efforts against P. vivax, P. malariae, and P. ovale. PMID- 2189002 TI - In defense of mucosal surfaces. Development of novel vaccines for IgA responses protective at the portals of entry of microbial pathogens. AB - A common mucosal immune system occurs in mammalian species, where antigen stimulation of BALT and GALT induces an exodus of specific lymphocytes that home to the various mucosal effector sites. These responses are finely regulated and T cells and cytokines are of central importance for ultimate plasma cell differentiation and for production of S-IgA antibodies in our external secretions. The current need for vaccines, including those to respiratory, gastrointestinal, and genitourinary tract infections as well as the universal efforts to develop immunity to HIV and AIDS, compels us to continue to better understand how we can use the common mucosal immune system to advantage for eventual prevention of infectious diseases. This article summarizes the various antigen delivery strategies and progress of oral vaccines for induction of protective mucosal immune responses to various viral and bacterial diseases. PMID- 2189003 TI - Edward H. Kass, M.D., eulogy. PMID- 2189004 TI - Amplification of HIV-1 provirus from cerebrospinal fluid and its correlation with neurologic disease. AB - The polymerase chain reaction (PCR) was used to detect human immunodeficiency virus type 1 (HIV-1) proviral sequences (gag and env) in nucleated cells from the cerebrospinal fluid (CSF) of 31 HIV-1-positive patients, and the results were compared with clinical and radiologic evidence of neurologic disease. Provirus was detected in 21 patients, of whom 20 had neurologic abnormalities. Provirus was not detected in another 6, all of whom were neurologically normal. No neurologic disease has developed in 4 of these 6 patients for whom 12.8 months of follow-up is available. PCR of CSF nucleated cells from HIV-positive patients provides early, rapid, direct evidence of neurologic involvement. PMID- 2189005 TI - Septic cortical thrombophlebitis. AB - Thrombosis of cortical veins has been postulated as an important cause of seizures and focal neurologic deficits in patients with bacterial meningitis. Diagnoses from autopsies, angiograms, and medical records at Massachusetts General Hospital, 1960-1984, were reviewed to identify patients with septic cortical thrombophlebitis. Only 10 confirmed cases of septic cortical vein thrombosis without sagittal sinus thrombosis were found. Meningitis was present in nine patients; Streptococcus pneumoniae was isolated from the blood or cerebrospinal fluid of five patients. Common clinical manifestations included fever, seizures, and focal neurologic signs. Half the patients survived, but three had persistent disabilities. Cortical vein thrombosis could be documented in only approximately 1% of 790 cases of bacterial meningitis. In 97 patients with meningitis who died and had autopsies, cortical thrombophlebitis was identified in 5%. In autopsied patients, other pathologic processes including arteritis, ventriculitis, cavernous sinus thrombosis, and cerebral infarctions were usually more prominent than venous thrombosis. Cortical thrombophlebitis does not appear to be the major cause of seizures or focal neurologic signs during bacterial meningitis. PMID- 2189006 TI - Increase of trimethoprim resistance among Shigella species, 1975-1988: analysis of resistance mechanisms. AB - Trimethoprim (TMP) resistance among Shigella species isolated from Finnish travelers increased from 3.0% in 1975-1982 to 42.0%-43.8% in 1987-1988. Of the 317 TMP-resistant Shigella isolates identified during 1975-1988, 175 (55%) collected in 1985-1987 and in 1988 were tested further. Almost all (98%) were highly resistant to TMP, suggesting a plasmid-mediated origin. The type I dihydrofolate reductase (DHFR) gene was detected in 85% of the isolates studied. Twenty-three percent of the type I DHFR-positive isolates failed to hybridize with a probe detecting only Tn7-derived sequences, suggesting that the type I DHFR gene may occur independently of transposon Tn7. Four of the five Shigella species isolated from travelers to Sri Lanka hybridized with the probe for type V DHFR gene, implying a local distribution of the type V DHFR gene. The type II and type III DHFR genes were not found among the isolates studied. Only 12% of the TMP-resistant Shigella isolates failed to hybridize with any of the DHFR gene probes used. PMID- 2189007 TI - A sensitive and specific DNA probe to identify enteroaggregative Escherichia coli, a recently discovered diarrheal pathogen. AB - The epidemiologic significance of enteroaggregative Escherichia coli (EAggEC) as a diarrheal pathogen has only recently come under study. Although EAggEC has been associated with persistent diarrhea in infants in some developing countries, additional studies are clearly needed. Until now, the only means of identifying EAggEC strains has been the cumbersome HEp-2 cell adhesion assay. The isolation and cloning of a 1-kilobase fragment from the plasmid of EAggEC strain 17-2 is described. This probe is 89% sensitive and 99% specific for EAggEC identification. Thus, this probe should greatly facilitate epidemiologic studies assessing the importance of EAggEC as a diarrheal pathogen. PMID- 2189008 TI - Detection of Shigella in feces using DNA amplification. AB - A rapid diagnostic method employing a polymerase chain reaction procedure (PCR) was used to identify Shigella and enteroinvasive Escherichia coli. This procedure amplified a region of the invasive-associated locus (ial) from a crude DNA extract of feces. A synthetic 21-base oligonucleotide corresponding to the ial gene sequence was shown to specifically hybridize only with enteroinvasive E. coli (EIEC) strains and Shigella species. Upon PCR amplification, a 320-base pair fragment was generated in DNA extracted from feces reconstituted with EIEC or Shigella flexneri but not in DNA from 70 normal stools lacking these organisms and could be readily detected by the ial probe. For identifying Shigella and EIEC, the PCR assay was 10(5)- and 10(2)-fold more sensitive than standard biochemical tests and the macrocolony hybridization assay, respectively. These findings demonstrate a novel methodology for rapid, sensitive, and culture independent diagnosis of diarrhea caused by these pathogens and underscores the utility of PCR in the diagnostic laboratory. PMID- 2189009 TI - Evidence for a role for secreted aspartate proteinase of Candida albicans in vulvovaginal candidiasis. AB - The presence of the secretory aspartate (acid) proteinase in the vaginal fluid of candidal vaginitis patients and controls was studied by ELISA and immunoblot (Western blot). In addition, a proteinase-deficient mutant strain of Candida albicans (IR24) was compared with the wild-type parent strain (10261) for ability to infect the vagina of pseudoestrus rats under estradiol treatment. Among the 67 women examined, proteinase was detected only in 22 harboring C. albicans (range, 42-233 ng/ml of vaginal fluid), at concentrations significantly higher in the 14 vaginitis patients than in the 8 asymptomatic fungal carriers. Western blots confirmed the presence of only one protein band of approximately 43 kDa, corresponding to that of the purified proteinase, in the ELISA-positive vaginal fluids. Experimental vaginal infection was significantly more extensive and persistent in rats infected with the proteinase-producer strain than in those challenged with the proteinase-deficient mutant, and the enzyme was detected in the vaginas of the former but not of the latter animals. Both strains 10261 and IR24 developed hyphal forms to a roughly similar extent during infection, and both showed a comparable adherence in vitro to vaginal and buccal epithelial cells. The clinical and experimental evidence support a role for secretory proteinase as a virulence factor in the pathogenesis of candidal vaginitis. PMID- 2189010 TI - Parasitologic findings in percutaneous drainage of human hydatid liver cysts. AB - Percutaneous drainage under ultrasonographic guidance was carried out on 12 patients with liver cysts and 1 with an abdominal cyst. In 8 the cyst was proved to be of hydatid origin by means of direct detection of parasites in the aspirated fluid. In these individuals a 95% ethanol solution was subsequently introduced into the cystic cavity and slowly removed over 30 min. Direct observation, staining for viability assessment, and in vitro isolation attempts were done both before and after the injection of the alcoholic solution, thus making possible the immediate evaluation of the protoscolicidal properties of the solution used. The procedure seems to be therapeutically successful, safe, and feasible. PMID- 2189011 TI - Pertussis in an adult man infected with the human immunodeficiency virus. AB - A 25-year-old man infected with the human immunodeficiency virus (HIV) presented with paroxysmal cough and dyspnea of 4-months duration. An extensive evaluation including bronchoscopy was negative. A nasopharyngeal swab was positive by direct fluorescent antigen detection and culture for Bordetella pertussis. Respiratory isolation, treatment with erythromycin, and prophylaxis of household contacts was used to eradicate the organism and prevent transmission. Pertussis should be considered as a cause of prolonged cough and dyspnea in patients with HIV infection. The course of this patient was consistent with the concept that cell mediated immunity is necessary for elimination of B. pertussis. PMID- 2189013 TI - Colony-forming cells with high proliferative potential (HPP-CFC). AB - Colony-forming cells with a high proliferative potential (HPP-CFC) have been defined by their ability to form large colonies in vitro (diameters greater than 0.5 mm and containing approximately 50,000 cells) in bone marrow cell cultures. The HPP-CFC have been characterized by: 1) a relative resistance to treatment in vivo with the cytotoxic drug 5-fluorouracil, 2) a high correlation with cells capable of repopulating the bone marrow of lethally irradiated mice, 3) their multipotential ability to generate cells of the macrophage, granulocyte, megakaryocyte and erythroid lineages, and 4) their multifactor responsiveness. The HPP-CFC have been described in both mouse and human bone marrow. These properties suggest that the HPP-CFC represent an important cell type in hematopoiesis and provide a model system, particularly in the human, for studying the properties of primitive progenitor cells in vitro. PMID- 2189012 TI - A safe and effective consecutive-infusion regimen for rapid quinine loading in severe falciparum malaria. AB - Recommended initial treatment of severe chloroquine-resistant falciparum malaria consists of a 4-h loading infusion of 20 mg of quinine dihydrochloride (salt)/kg of body weight. To achieve and maintain therapeutic blood quinine concentrations (10 mg/l) safely and rapidly, a consecutive-infusion regimen (7 mg of salt/kg of body weight over 30 min followed by 10 mg of salt/kg of body weight over 4 h) based on pharmacokinetic parameters in cerebral malaria has been suggested. This regimen was evaluated in 16 adults (6 male, 10 female; mean age, 25.9 years) with severe falciparum malaria. Plasma quinine concentrations (mean +/- SE) were 8.7 +/- 1.2 mg/l at 30 min and 11.0 +/- 1.8 mg/l at 4.5 h. There was no electrocardiographic evidence of serious cardiotoxicity during the 4.5-h infusion period, and systolic blood pressure fell by greater than 10 mm Hg in only one patient. Parasite clearance in 13 surviving patients (median count on admission, 438 x 10(3)/microliters; range, 500-122 x 10(4) took an average of 71 h (range, 9 115). This regimen is safe, effective, and suitable for use in an intensive care unit. PMID- 2189014 TI - Tiazofurin: biological effects and clinical uses. AB - Inosine 5'-phosphate dehydrogenase (IMPDH) activity is increased in all cancer cells. It is the rate-limiting enzyme of guanosine triphosphate (GTP) biosynthesis, and therefore, a sensitive target of chemotherapy. Tiazofurin selectively blocks IMPDH activity. Tiazofurin was found to have an antiproliferative effect on tumor cells in vitro and in the murine system. Based on these findings, Phase I trials were started elsewhere in patients with solid tumors, but were discontinued because of toxicity. In leukemic patients, we were able to demonstrate a good correlation between biochemical parameters (i.e., decline in IMPDH activity and GTP concentrations in blast cells) and clinical response. The most consistent responses to therapy were seen in patients with myeloid blast crisis of chronic myeloid leukemia. Severe toxicity was seen in the earlier patients in the study. However, better patient selection, limitation of treatment duration and earlier recognition and treatment of complications have now made it possible to administer tiazofurin without undue toxicity. PMID- 2189015 TI - Wegener's granulomatosis of the head and neck. AB - Wegener's granulomatosis is an uncommon systemic vasculitis with granuloma formation that has many manifestations in the head and neck. The otolaryngologist may be the first physician called upon to examine such a patient. Although this disease was previously fatal, treatment with cyclophosphamide and steroids has produced response rates of 93%. PMID- 2189016 TI - Coronary stents: a review of recent developments. AB - Coronary stent placement is one of the newest treatments for occlusion of the coronary arteries. This technique has the potential to minimize restenosis and reduce or eliminate abrupt closure, common complications of percutaneous transluminal coronary angioplasty (PTCA). Initial studies in Europe in the mid 1980s indicated a problem with restenosis due to thrombosis and intimal hyperplasia in stented arteries. Recent investigational studies of the Palmaz balloon-expandable stent in the United States, however, show great promise in solving those problems. It is hoped that coronary stenting may be used for lesions now treated by coronary artery bypass graft surgery, as well as for improving the outcome of PTCA. PMID- 2189017 TI - Percutaneous transluminal coronary angioplasty: an expanding role in complex coronary artery disease. AB - Since its inception in 1977, percutaneous transluminal coronary angioplasty (PTCA) has played an increasing role in the treatment of complex single and multivessel coronary artery disease. Many patients, previously treatable only by coronary artery bypass grafting, are now successfully treated with PTCA in the cardiac catheterization laboratory. Two important limitations to the procedure, acute closure and restenosis of the dilated vessels, persist. However, studies with lasers, intracoronary stents, perfusion catheters, thrombolysis, and antiplatelet drugs are ongoing in an attempt to minimize these complications. In addition, studies are now ongoing comparing PTCA with bypass grafting to further define the role of each in coronary disease. PMID- 2189018 TI - Weight loss in nursing home patients: prognostic implications. AB - Weight loss is commonly used as a screening tool to assess quality of care and nutritional status in the nursing home setting. To evaluate the prognostic value of weight loss, the charts of 199 nursing home patients (414 nursing home patient years; mean age 87 years) were reviewed over a 3-year period. Weights recorded at nursing home admission and during the study period were compared with weights at the time of acute care hospitalization, transfer between levels of nursing home care, change in level of functional status, and death. There were no significant changes in weight before acute care hospitalizations, although patients who died lost an average of 10% of their body weight from the time of nursing home admission (P less than .001). In addition, weight loss was associated with decreased functional ability and transfer to a higher level of nursing home care. Despite the association of weight loss with subsequent morbidity and mortality, moderate weight loss of up to 20% was a poor predictor of mortality. Although weight loss is routinely used as a screening tool in the nursing home setting, it is not a sensitive marker for underlying disease. The efficacy of active intervention in nursing home patients who lose weight requires further study. PMID- 2189019 TI - Perinatal transmission of bacterial sexually transmitted diseases. Part II: Group B streptococcus and Chlamydia trachomatis. AB - Sexually transmitted diseases (STDs) have reached epidemic proportion in the United States and have captured the attention of both laypersons and health care professionals. Of special concern is that most STDs can be transmitted vertically to the offspring of infected mothers. Since the advent of acquired immunodeficiency syndrome, other STDs have been at risk of being relatively disregarded. This paper, the second of two parts, reviews issues of prevalence, morbidity, mortality, diagnosis, prevention, and treatment of group B streptococcal and chlamydial infections as they affect the maternal-fetal dyad. PMID- 2189020 TI - Microvasculature of the nasal salt gland of the duckling, Anas platyrhynchos: quantitative responses to osmotic adaptation and deadaptation studied with vascular corrosion casting. AB - The three-dimensional microvasculature of the nasal salt gland of the duckling was studied by vascular corrosion casting and scanning electron microscopy. Changes in the vascular volume of the gland in response to osmotic stress were also determined using cast weights and densities. The richly vascularized gland is supplied on its medial surface by large branches of the supraorbital and ethmoidal arteries. Numerous arterial branches enter the gland and distribute to lobes via the interlobar connective tissue. Lobar arterioles penetrate to the periductal areas of the lobes before dividing into capillaries supplying the ductal epithelium and secretory tubules. Capillaries envelope the secretory tubules and run radially from the ducts toward the lobe periphery, so that blood flows counter to the tubular secretion. Blood is collected via venous plexuses seen as distinct drainage units on the periphery of each lobe. Veins exhibit large numbers of bicuspid valves. Following 1 day and 4 days of osmotic loading (feeding 1% NaCl), vascular volume of the gland increased fivefold and ninefold, respectively, a response that precedes and exceeds that of the gland weight or Na,K-ATPase activity. When salt water-adapted ducklings were fed fresh water for only 24 hr (deadaptation), vascular volume fell to 2.8 times the control level. Changes in blood flow to the gland during osmotic adaptation and deadaptation are rapid and dramatic and may represent the initial steps in the control of gland secretion. PMID- 2189021 TI - Insulin cells are found in the main and accessory urinary bladders of the painted turtle, Chrysemys picta. AB - Insulin has been localized immunocytochemically to cells in the main and accessory urinary bladders of the painted turtle, Chrysemys picta, and represents an unusual addition to the specturm of regulatory peptides associated with the urinary bladder. These stellate to fibroblastoid cells often possess neural-like processes and are similar in morphology to neurotensin cells found in Chrysemys and Pseudemys urinary bladders. Radioimmunoassay of 2M acetic acid extracts of bladder tissue indicate that the insulin concentration of accessory bladder is several-fold greater than main bladder but considerably lower than the insulin content of pancreas. Pieces of accessory bladder incubated in vitro exhibit a stable insulin release into the medium over 1 hour, but release is unaltered by known insulin secretagogues. It is tempting to postulate an endocrine or paracrine regulatory function for these cells, but at present their role in Chrysemys bladder function remains unknown. PMID- 2189022 TI - Characterization of the DA26 gene in a hypervariable region of the Autographa californica nuclear polyhedrosis virus genome. AB - A region of the baculovirus Autographa californica nuclear polyhedrosis virus genome that is frequently found to be altered after serial passage of the virus in cell culture was characterized. Sequence analysis of this region of the genome in wild-type and mutant viruses revealed that some of the mutations affected a 675 bp open reading frame, designated DA26. The DA26 gene was disrupted both by deletion and by insertion of sequences that resembled transposable elements. Northern blot analysis of DA26 showed that it was expressed very early after infection. DA26-specific transcripts could be detected after the 1 h viral adsorption period upon infection of cultured Trichoplusia ni cells. These transcripts were mapped by nuclease protection assays. A recombinant virus was constructed in which DA26 was disrupted by insertion of the Escherichia coli lacZ gene. This virus was viable in both T. ni and Spodoptera frugiperda cells and analysis of the kinetics of protein synthesis revealed no differences between wild-type and recombinant viruses. The disruption of DA26 also did not interfere with the ability of the virus to infect T. ni or S. frugiperda larvae. PMID- 2189024 TI - Studies on the castability of Co-Cr alloy for cast plates. Part 2: Effect of form of sprue attachment to the wax pattern. AB - Co-Cr alloy is used more frequently than Ni-Cr alloy as a non-precious alloy for cast plates in Japan. However, since the melting point of Co-Cr alloy is very high, about 1300 degrees C, and since it oxidizes easily, a vacuum-pressure casting machine capable of melting this alloy in a reducing atmosphere has recently been developed. Using this vacuum-pressure casting machine, the authors studied the effects on the castability of Co-Cr alloy due to the form of sprue attachment to the wax pattern. The results clarified that in the vacuum-pressure casting method, the form of sprue attachment to the wax pattern has a significant effect (p less than 0.01) on the castability of Co-Cr alloy. PMID- 2189023 TI - Failure to demonstrate human T cell lymphotropic virus type I in multiple sclerosis patients. AB - The polymerase chain reaction (PCR) technique was employed in searching for human T cell lymphotropic virus type I (HTLV-I) gag, env and pol sequences in samples of DNA prepared from two HTLV-I seropositive patients with tropical spastic paraparesis (TSP), the Swedish multiple sclerosis (MS) patients who recently have been reported to be PCR-positive for HTLV-I gag and env sequences, and eight healthy individuals. Precautions were taken in order to reduce the risk of cross contamination in the PCR. In the two TSP patients strong signals were obtained with gag, env and pol amplification primers and detection probes. In MS patients and healthy individuals, no signals were obtained with gag and env. In occasional experiments, weak signals were seen for the pol segment for a single MS patient and/or healthy individuals, but these signals were not reproducible in subsequent experiments. Thus, the present data do not confirm the presence of HTLV-I sequences in MS patients. PMID- 2189025 TI - Granular cell tumor of the tongue: an electron microscopical and immunohistochemical study. AB - Granular cell tumor of the tongue in a 29-year-old woman is reported including details of studies using electron microscopy and immunohistochemistry. Immunohistochemically, the tumor cells showed moderate positivity for S-100 protein. Electron microscopically, basal lamina, angulate bodies, myelin-like figures and axon-like structures were observed in the tumor. These findings may indicate that this tumor is a lesion of Schwann cell origin. The Japanese literature on oral granular cell tumor is also reviewed and discussed. PMID- 2189026 TI - Hypertension: the cause of the J-curve. AB - Many studies have established that mortality from heart attacks is related to diastolic blood pressure in a J-curve with increased mortality at low as well as high pressures. This has been observed in untreated as well as treated patients and a similar phenomenon has been found in large population studies. Two hypotheses to account for this curve have been advanced. The direct causation hypothesis attributes the increased mortality at low pressures to low coronary perfusion. The reverse causation hypothesis attributes the curve to a subgroup of patients with low blood pressures as a result of pre-existing disease. This controversy is still unresolved and needs a prospective trial to decide the issue. PMID- 2189028 TI - Renin-secreting retroperitoneal leiomyosarcoma: an unusual cause of hypertension. AB - A 41 year old man with severe hypertension due to a renin-secreting retroperitoneal leiomyosarcoma is described. Clinical, immunohistochemical, electron microsopic and autopsy findings are presented. The origin of juxtaglomerular cells from vascular smooth muscle is briefly discussed. PMID- 2189029 TI - Hypertension due to a renal renin-secreting tumour. AB - We report a case of a 25 year old man referred to our department because of a blood pressure of 162/122 mmHg, found during a general physical examination. A renal renin-secreting tumour was found to be the cause of the hypertension. It had a diameter of 4 cm and was enucleated from the right kidney. Subsequently the blood pressure returned to normal levels. Histological examination revealed a hemangiopericytoma. PMID- 2189027 TI - Evaluation of the efficacy and safety of enalapril plus hydrochlorothiazide plus methyldopa vs standard triple therapy in the treatment of moderate to severe hypertension: results from a multicentre study. AB - We report the results of a randomized, double-blind, parallel group multicentre study in 120 patients with moderate to severe hypertension, comparing two different types of antihypertensive treatment: a) the standard 'triple therapy' with hydrochlorothiazide, propranolol and hydralazine, and b) the combination of an ACE inhibitor, enalapril with hydrochlorothiazide (HCTZ) and methyldopa. The two regimens caused similar degrees of blood pressure reductions. The only significant difference between the two groups was heart rate due to the bradycardiac effect of propranolol in the group treated with the standard 'triple therapy'. Only 3.4% of patients receiving the regimen of enalapril, HCTZ and methyldopa were withdrawn from the study for adverse reactions, against 10% of patients on HCTZ, propranolol and hydralazine. Four cases of hypokalaemia in the enalapril group and 19 in the propranolol group were reported: so enalapril seemed to ameliorate the hypokalaemic effect of HCTZ. The overall analysis of the study results shows that the treatment based on enalapril, HCTZ and methyldopa is as efficient and better tolerated than the established regimen of HCTZ, propranolol and hydralazine. PMID- 2189030 TI - [The tidal volume, arterial blood gas and functional residual capacity changes during negative extra-thoracic pressure ventilation and positive airway pressure ventilation]. AB - Eight patients, of ASA physical status I or II soon after total knee replacement under general anesthesia, were studied to compare negative extra-thoracic pressure ventilation (NETPV) with positive airway pressure ventilation (PAPV). The measured parameters during the two ventilatory modes were tidal volume, arterial blood gas and functional residual capacity change (delta FRC). Tidal volume obtained during NETPV was 60 to 80% of that during PAPV at the same absolute values of peak pressure. delta FRC obtained during NETPV was 30 to 40% of that during PAPV at the same absolute values of end-expiratory pressure. A decrease in the esophageal pressure was 4 to 11cmH2O at an end-expiratory negative extra-thoracic pressure of -10 to -20 cmH2O. When the patients were ventilated with the same values of minute ventilation on NETPV and PAPV, there was no significant difference in blood gas values. These findings suggest that efficiency of NETPV is less than that of PAPV at the same absolute working pressure but pulmonary gas exchange of NETPV is almost equal to that of PAPV at the same minute ventilation in the normal lung. PMID- 2189032 TI - [Ultrasonic observation of the renal artery]. PMID- 2189031 TI - [Ultrasonography of the extremities: nontumor lesions]. AB - Ultrasonographic imagings of non-tumor disorders in extremities were reviewed and discussed. All cases underwent surgery. In our retrospective evaluation, US was found to be effective in cases of tendon injuries, articular osteochondritis, tenosynovitis and the displacement of chondral navicula in infantile club foot, etc. PMID- 2189033 TI - Progression of chronic renal failure in man. PMID- 2189034 TI - Basement membrane alterations during development and regression of tubular cysts. AB - Tubular cysts consisting of dilatation of the collecting ducts at the level of the subcapsular zone of the kidney were induced in newborn rabbits by a single injection of methylprednisolone acetate. We describe here the structural and compositional modifications of the tubular basement membrane (BM) during the formation, growth, and regression of the tubular cysts. During development of the tubular cysts the cystic BM appeared thickened and multilayered, with numerous matrix vesicles. Alcian blue- (AB) and ruthenium red- (RR) positive material distributed differently along the BM of control and cystic tubuli. While the amount of RR-positive material appeared increased in the cystic BM, no differences in the intensity of the AB staining could be discerned between normal and cystic tubuli. Immunofluorescent staining for laminin and type IV collagen appeared to be slightly decreased in the cystic tubuli. However, the amount of fibronectin appeared clearly increased. These changes in the cystic BM appear at the beginning of the tubular dilatation and are not observed in other renal BM. We suggest that there is a causal relationship between the modifications of the BM and the development of the tubular cysts. Glucocorticoids appear to modify the synthesis and/or secretion of the BM components. An abnormal BM should modify the spatial and chemical signals encoded within the BM that, in turn, could lead to abnormal behavior of the tubular cells. This may result in a loss of the normal developmental constraints imposed upon the tubular epithelium, which then undergoes cystic dilatation. During the regression of the cysts, the abnormalities of the BM progressively disappear. The sharp increase in the number of interstitial cells, which show close relationships with the components of the BM, suggests that these cells may be involved in the removal of the cyst BM. PMID- 2189036 TI - Dietary fat, hypertension, atherosclerosis. PMID- 2189035 TI - Detection of nephritogenic antigen from the Lewis rat renal tubular basement membrane. AB - Immunopathogenicity of trypsin-solubilized or non-solubilized renal tubular basement membrane (TBM) of the Lewis (LEW) rat was investigated. Autoimmune tubulointerstitial nephritis (TIN) was induced in BALB/c mice by immunization with trypsin-solubilized LEW rat TBM, while immunization with non-solubilized TBM did not produce the disease. Based on this preliminary experiment we studied the characterization of immunogenic and nephritogenic TBM antigen of the LEW rat. TIN was characterized by severe mononuclear cell infiltrates with multi-nucleated giant cells in the interstitium, tubular destruction and intensive IgG and C3 deposits along the TBM. Anti-TBM antisera and eluate from the nephritic mouse kidneys reacted with the TBM of normal LEW rat kidney by immunofluorescence. LEW rat TBM was also detected immunofluorescently by using antisera from BALB/c mice immunized with autologous trypsin-solubilized TBM. A competitive inhibition test revealed a higher titer of anti-TBM antibody in the eluate than in the adsorption treated antisera per microgram IgG. Immunoblotting showed one reactive band with a molecular weight of 45,000 daltons, and the blotting patterns in tryptic TBM of the Brown Norway (BN) and LEW rats appeared similar. Amino acid analysis of nephritogenic LEW rat tryptic TBM showed that it contained no hydroxyproline and hydroxylysine, suggesting that this TBM preparation was not collagenous. These findings suggest that tryptic digestion contributes to the release of nephritogenic antigen from the LEW rat TBM and that this antigen system might participate in the immune system involved in the anti-TBM associated TIN that is well known to be induced by non-digested TBM of TBM antigen positive animals. PMID- 2189037 TI - Does a high P/S ratio diet lower blood pressure? AB - The answer to the question the title of this paper puts is: No a P/S ratio diet alone does not lower blood pressure! Although a number of cross-sectional and other studies do suggest that there is a relationship between P/S ratio and blood pressure it is not possible in these studies to eliminate the potentially confounding effects of other aspects of diet and lifestyle which are also either different or affected by the experiment. Most of the evidence from properly controlled randomised experimental studies do not provide support for an effect of an elevation of the dietary P/S ratio alone on blood pressure. These experiments have been conducted at various levels of total fat intake, across a range of blood pressures (but not very high blood pressures) and for both a short or longer duration. The levels of polyunsaturated fats have also varied from modest increases to quite substantial increases. It is therefore unlikely that aspects of sample selection, range of dietary change or length of observation can account for the failure of these studies to show an effect on blood pressure. From other observational and experimental studies it is apparent that dietary change can affect blood pressure. It may be that combinations of dietary factors need to occur in synchrony to affect blood pressure. It is therefore possible that a high P/S ratio diet in combination with for example potassium, calcium or magnesium or other dietary factors may influence blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189038 TI - Dietary fat and blood pressure in humans. AB - The regulation of blood pressure by dietary means represents an important approach toward the reduction of morbidity and mortality of heart disease. The results of our dietary intervention studies demonstrated that a lowered saturated fat, higher polyunsaturated fat diet had a lowering effect on both systolic and diastolic blood pressure, and a lowering effect on blood lipids. These beneficial effects were accomplished without drastic changes in the typical Western diet. The amount of meat, dairy products, fish and eggs was not altered from the usual intake, while the intake of fruits, vegetables and grains increased. As a consequence of altering the diet, we have found that the blood pressure lowering effect appears to be mediated through linoleic acid (n-6). It is evident from these results that the role of diet must be given serious consideration for the control of blood pressure. PMID- 2189039 TI - Polyunsaturated fatty acids and cardiovascular function in man. AB - Dietary supplementation with either n-6 or n-3 polyunsaturated fatty acids has been reported to lower blood pressure in man, and to confer benefits in atherosclerotic vascular disease. Such effects have been suggested to be due to altered in vivo production of vasoactive prostaglandins, but this hypothesis has not been tested previously. Epidemiologic data are often quoted as showing lower blood pressure in populations with a high consumption of fish, but such conclusions are less clear from the primary data. This review presents some of the population studies on the relationship between fish intake, hypertension and vascular disease, discusses problems in studying blood pressure in dietary intervention trials, and reviews the published literature on reducing blood pressure and vascular reactivity with dietary n-3 supplements in volunteers. Recent work addressing a number of controversial points is presented, with the conclusion that pharmacologic doses of n-3, but not n-6, fatty acids can lower blood pressure in humans, but probably do not do so through directly lowering vascular reactivity to catecholamines or increasing the synthesis of vasodilator prostaglandins. PMID- 2189040 TI - Blood pressure-lowering effect of mackerel diet. AB - Several dietary studies were designed to evaluate the blood pressure-lowering effect of long-chain n-3 polyunsaturated fatty acids (PUFA) under similar experimental conditions. In the first 3 studies, 15 normotensive volunteers, 14 patients with mild essential hypertension and 15 patients with hyperlipoproteinemias (HLP, phenotypes IIa, IIb, IV and V), respectively, were put on isocaloric diets supplemented either with 2 cans/day of commercially available mackerel fillet in tomato pulp for 2 weeks or with 2 cans/day of herring fillet in tomato pulp for 2 weeks in a crossover regimen. Besides a significant fall of serum cholesterol and triglycerides systolic as well as diastolic blood pressure (BP) from normotensive subjects and systolic blood pressure from mildly hypertensive and hyperlipemic patients was significantly decreased at the end of the mackerel diet providing the twofold higher dose of long-chain n-3 PUFA. Plasma noradrenaline and thromboxane B2 were likewise depressed, the former in normotensive volunteers, the latter in mildly hypertensive patients. In hyperlipemics with an initial systolic BP of 160 mmHg and above the hypotensive effect appeared more pronounced as compared to hyperlipemics with systolic blood pressure below 160 mmHg. In a fourth (long term) study providing as low as 3 cans/week of mackerel for 8 months systolic and diastolic BP of 12 male patients with mild essential hypertension appeared significantly reduced at the end of the dietary period. This indicates that even a low-dose regimen might effectively lower mildly elevated blood pressure over a long-term period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189041 TI - Concordant dyslipidemia, hypertension and early coronary disease in Utah families. AB - A detailed family history questionnaire collected from families of 35,000 sixteen year old high school students in Utah was used to identify population-bases sibships with two or more living adults affected with hypertension under age 60 or coronary artery disease before age 55. Detailed clinical and biochemical evaluations performed during a four-hour visit to a research clinic provided data to test for concordant abnormalities in siblings with either early hypertension or early coronary heart disease. A new syndrome, familial dyslipidemic hypertension (FDH), was found in 48% of the hypertensive sibships. In these FDH subjects, 68% had HDL-cholesterol below the 10th percentile, 49% had triglyceride level above the 90th percentile, and 27% had LDL levels above the 90th percentile. When compared to normolipidemic hypertensive subjects, persons with FDH had significantly elevated fasting plasma insulin levels, increased subscapular skinfold thickness, increased knee width and wrist circumference, and increased levels of VLDL cholesterol and apolipoprotein B. In coronary sibships, concordant abnormalities for lipids were consistent with familial combined hyperlipidemia in 30-40% of sibships, FDH in 15-45% of sibships, and low HDL-C (with normal cholesterol) in 10%. Concordant normal lipids were found in only 15% of sibships. These data suggest that inherited metabolic abnormalities likely explain some co-aggregation of hyperinsulinemia, obesity, hypertension, and early coronary heart disease. Current knowledge also suggests these metabolic abnormalities could be treated or prevented with appropriate modification in lifestyle factors such as diet and exercise as well as through the use of prescription medications. PMID- 2189042 TI - Theoretical analysis of the effect of convective flow on solute transport and insulin release in a hollow fiber bioartificial pancreas. AB - The bioartificial pancreas, in which transplanted pancreatic tissue or isolated cells are cultured on a hollow fiber membrane, is an attractive approach to restore physiologic insulin delivery in the treatment of diabetes. Insulin response in prototype devices has been unacceptable due to the large mass transport limitations associated with the membrane and the surrounding shell region. Although available theoretical analyses provide some insight into the combined effects of transport and reaction in the bioartificial pancreas, they cannot quantitatively account for the effects of convective recirculation flow, complex intrinsic insulin secretory kinetics, and non-uniform distribution of pancreatic cells. We have developed a detailed model for glucose and insulin transport and insulin secretion in the hollow fiber bioartificial pancreas based on the solution of the mass and momentum conservation equations describing flow and transport in the lumen, matrix, and shell. Model predictions are in good agreement with literature data obtained in a hollow fiber device with minimal radial convective flow. Although no quantitative data are available for a device with significant radial convection, model simulations demonstrate that convective recirculation flow can dramatically improve insulin response, allowing the device to accurately capture the bi-phasic insulin secretion characteristic of the normal physiologic response. Results provide fundamental insights into the coupling between kinetics and transport in the hollow fiber system and a rational basis for the design of clinical devices. PMID- 2189043 TI - Combretodendron Africanum bark extract as an antifertility agent. I: Estrogenic effects in vivo and LH release by cultured gonadotrope cells. AB - An aqueous extract from the stem bark of Combretodendron africanum was prepared to investigate its potency as a regulator of fertility. The intraperitoneal LD50 in mice was 95.2 +/- 4.3 mg/kg. Daily i.p. injections of 50 mg/kg promoted a significant increase in the uterine weight of 25 day-old female rats while pituitary weight remained unaffected. Similar injections for 21 days to mature females blocked the estrous cycle in the luteal phase with a mean length of efficiency of 15 days and decreased plasma LH and FSH levels. Regular cycles were restored 10 days following the last injection. C. africanum extract was shown to compete with estradiol and with progesterone on uterine receptors. Consequently, it is thought to contain substances exhibiting estrogenic (and possibly anti estrogenic) potency. The effects of the extract on LHRH-induced release were investigated on cultured pituitary cells. Although gonadotropin release was amplified, the extract itself appeared as to be a potent secretagogue not requiring LHRH receptors. It follows that the active molecules contained in C. africanum extracts may be different from classical steroid estrogens. PMID- 2189044 TI - The potential use of thalidomide in the therapy of graft-versus-host disease--a review of clinical and laboratory information. AB - This article reviews the historical development of thalidomide as an immunosuppressive agent and the current state of knowledge of thalidomide as an anti-graft-versus-host disease (GVHD) agent. The evidence suggests that metabolites of thalidomide act at an early stage in the antigen recognition activation pathway of graft T lymphocytes and down regulate normal lymphocyte responses. This effect seems to have beneficial effects in both acute and chronic GVHD, but the optimal mode of use in the clinical setting remains to be determined. PMID- 2189045 TI - p75c-myb expression in leukemia-lymphoma cells correlated with proliferation and differentiation. AB - Monoclonal antibodies (McAbs) against a part of v-myb gene product were prepared for the detection of human c-myb gene product (p75c-myb). Western blotting analyses with these McAbs were performed on human leukemia-lymphoma cells. All T cell lines were positive in p75c-myb expression. B-cell lines were variable, myeloid and erythroid cells were positive although the amount of expressed p75c myb was less than the T-cell lines. Cells isolated from patients were positive in expression except for cells from acute myeloblastic leukemia with maturation (AML M2), acute hypergranular promyelocytic leukemia (AML M3) and erythroleukemia (AML M6) developed from myelodysplastic syndromes. Differences in p75c-myb expression seemed to depend upon the differentiation stage and distinctive lineage from which each cell line had been established. The p75c-myb expression in HL60 (acute promyelocytic leukemia cell line) showed remarkably high at logarithmic growth. When examined with HL60, p75c-myb expression significantly decreased during the differentiation induced by 12-O-tetradecanoylphorbol-13-acetate or retinoic acid. These results suggest that p75c-myb expression plays a crucial role in hematopoietic cell proliferation and differentiation and that multiple mechanisms including aberrant expression of p75c-myb is involved in leukemogenesis. PMID- 2189046 TI - Immunoreactive lactoferrin in resting, activated, and neoplastic lymphocytes. AB - Lactoferrin (Lf) in lymphocytes was assessed with immunofluorescence/flow cytometric technique. Surface Lf was detected primarily among B-cell-enriched preparations. Tonsillar B-cells of different densities expressed surface Lf similarly. Very small percentages of CALLA+ ALL, HCL, or EBV-transformed B-cells expressed surface Lf, whereas B-CLL lymphocytes had the highest percentages of surface Lf positivity. Few resting, cultured, or neoplastic T-lymphocytes expressed Lf. The pattern of immunofluorescence and analyses of surface and total cellular immunoreactive Lf indicated that Lf is associated primarily with the lymphocyte surface. The percentage and/or intensity of surface Lf-specific fluorescence were not significantly altered in B- or T-cells by incubation with physiologic concentrations of differric Lf, and the percentages of Lf-positive cells detected in respective subjects remained stable over time. Surface Lf positivity was unrelated to the expression of other surface antigens (except those marking B- or T-cell lineage) or cell cycle. Expression and/or binding of Lf in B-lymphocytes may become increased during certain stages of cell maturation. PMID- 2189047 TI - Synergistic interactions allow colony formation in vitro by murine haemopoietic stem cells. AB - A clonogenic assay for cells that give rise to macroscopic colonies in agar or methyl cellulose cultures using untreated, normal murine bone marrow as a source of stem cells is described. We have characterized the clonogenic cell, which has been designated CFU-A, by comparing its properties with those of multipotential stem cells (assayed as CFU-S) and lineage-restricted progenitor cells (assayed as GM-CFC). The investigations have included assessment of proliferative status and response to CFU-S proliferation regulators, response to 5-fluorouracil, buoyant cell density, radial distribution in the femur and response to ionizing radiation. We conclude that the CFU-A has properties in common with CFU-S that differ from those of GM-CFC. The data are consistent with the CFU-A assay detecting part of the multipotential stem cell population also detected by spleen colony formation. PMID- 2189048 TI - Lymphocytes and bronchial hyperresponsiveness. AB - Non-specific bronchial hyperresponsiveness can be defined as an increased responsiveness of the respiratory airways to physical, chemical and pharmacological stimuli. It is a characteristic feature of asthma. Knowledge of the mechanisms contributing to bronchial hyperresponsiveness can provide an insight into the pathogenesis of asthma and could lead to an improved therapy. Several abnormalities have been postulated to underlie the hyperresponsiveness, such as a beta-adrenoceptor dysfunction, hyperreactivity of airway smooth muscle, epithelial dysfunction or damage, increased reflex bronchoconstriction, mucus plugging and mucosal oedema. It is possible that more than one of these abnormalities or other, as yet unknown, mechanisms are involved. In contrast to the role of lymphocytes in the regulation of IgE antibody production, the role of these cells in bronchial hyperresponsiveness has received little attention. We review evidence indicating that lymphocytes are involved in the development of non-specific bronchial hyperresponsiveness in some animal models and in patients with asthma. PMID- 2189049 TI - Immunomodulation by cocaine--a neuroendocrine mediated response. AB - Cocaine acts directly on lymphoid cells and indirectly modulates the immune response by affecting the level of neuroendocrine hormones. In vitro, very high concentrations of cocaine inhibit different immune responses, while plasma levels following cocaine use have no effect. The results of the few published in vivo studies are contradictory, showing stimulatory, suppressive or no effect on lymphoid cells. The indirect effects of cocaine on the immune system could be mediated by ACTH, beta-endorphin and corticosterone. Anorectic effect associated with nutritional deficiencies of drug users could additionally affect the immune response by cocaine. PMID- 2189050 TI - An inhibitor of T lymphocyte blastogenesis derived from the unfertilized ova of Shad (Alosa sapidissima). AB - Unfertilized ova from Shad, a North Atlantic herring, contains a cytostatic inhibitor of T lymphocyte blastogenesis. The inhibitor has an estimated molecular weight of 10,000-30,000 Da, is heat stable, non dialyzable, and resistant to protease digestion and periodate oxidation. Although the inhibitor functions at an early metabolic event in T lymphocyte mitogenesis, it does not appear to interfere with thymidine transport, antagonize lectin binding to lymphocyte surface receptors, or interfere with the function of an essential serum component in the cell culture media. PMID- 2189051 TI - The physiology and mechanisms of the stress-induced changes in prolactin secretion in the rat. AB - It is well known that stress in a number of forms induces the secretion of prolactin (PRL) in a number of species. What is not well known is that under certain conditions stress will also induce a decrease in PRL secretion. The conditions whereby stress decreases PRL are those where PRL secretion is elevated such as during the proestrous afternoon surge and during the nocturnal surge of pseudopregnancy. The physiologic significance of the stress-induced increase of PRL is suggested to be important in maintaining the competence of the immune system. The significance of the stress-induced decrease of PRL does not appear to have a major consequence on the physiology of reproduction in the rat and it is suggested that future studies be directed towards its significance in the immune system. The literature is reviewed dealing with the regulation of PRL secretion with emphasis on the factors that generate PRL surges in the rat. In addition the mechanism(s) of the stress-induced increase and decrease is (are) also examined. A hypothesis is presented suggesting an interaction between tuberoinfundibular dopamine secretion and a hypothalamic prolactin releasing factor in the generation of PRL surges and the differential effects of stress on PRL secretion. PMID- 2189052 TI - Microcirculatory considerations in NMR flow imaging. AB - Regional flow estimation can be accomplished either by measuring the concentration of a deposited tracer whose extraction during transit through the organ is 100%, or by observing the time course of concentration of a tracer whose transport passage through the organ is flow-limited. The deposition method is simpler and applies not only to microspheres or other large particles that lodge in the microcirculation, but also to molecular markers which are trapped. It has the advantage of having substantial time in which to observe the local concentrations by external detection. In contrast, flow-limited markers must traverse the tissue without barrier limitation or other diffusional influence on the exchange. When the marker is limited strictly to the intravascular space, the transit time through the organ is short and observations must be made rapidly with a high resolution technique. An indicator which distributes throughout a large volume of distribution within the tissue has a slower washout, providing more time in which to make observations; tracer water is a suitable marker, except perhaps in the brain. For flow measurement by NMR, markers which fulfill these criteria without causing side effects are needed. PMID- 2189053 TI - Measurement of tissue blood flow using intravascular relaxation agents and magnetic resonance imaging. AB - Simple concepts of indicator-dilution techniques are described, and the theoretical basis of measuring regional blood flow via transit time measurements of a blood pool marker is discussed. Using very fast imaging of the effects of an appropriate and efficient relaxation agent, the concentration-time curve of the agent can be quantified. Preliminary measurements of the transit of superparamagnetic iron oxide through a rat brain at 2.0 T have been obtained. There are problems, however, in relating the NMR signal change to the tissue concentration of an intravascular relaxation agent when there is not fast exchange of the tissue water with the water in the vasculature, or when the precise efficacy of the agent varies with the geometrical arrangement of the capillaries. Studies of the effects of superparamagnetic iron oxide particles in different media confirm that the in vivo efficacy varies among different tissues, which complicates their use as blood flow markers. PMID- 2189054 TI - Computer-assisted adult medical diagnosis: subject review and evaluation of a new microcomputer-based system. AB - Three decades after the conceptual foundation was laid for computer-aided diagnosis, some of its potential has been realized. Systems based on probabilistic reasoning have been developed and applied within limited domains (e.g., acute abdominal pain) and for the general diagnosis of systemic disorders. Less progress has been made in the development and application of diagnostic systems based on "artificial intelligence", reflecting theoretical limits to this application of computers to medicine and the enormity of the task. The presently available probabilistic systems have recently been joined by a new microcomputer based system, MEDITEL Computer-Assisted Diagnosis, Adult System. The performance of this system was evaluated with both clinical-pathologic conference cases and consecutive admissions with undiagnosed illnesses. The correct diagnosis appeared on the list generated by the system in 80 to 90% of the cases. Experience with this and other systems illustrates current issues in the evaluation of computer systems for aid in diagnosis and of computer-based medical "expert" systems in general. These issues include physician acceptance of these systems and the ethical, legal, and regulatory aspects of computer system application. We conclude that, in appropriately selected cases, the accuracy and efficiency of physician diagnosis can be enhanced with computer assistance, and the risk of overlooking the correct diagnosis can be reduced. PMID- 2189055 TI - Osteoporosis in men: diagnosis, pathophysiology, and prevention. AB - Osteoporosis in men is a significant problem in clinical medicine and in society in general. Systematic consideration of the differential diagnosis of osteopenia and osteoporosis in men is appropriate in every affected patient. Dynamic bone histomorphometry has diagnostic usefulness in some patients and has provided important pathogenetic implications by study of bone remodeling and turnover. Review of the multifactorial pathophysiology of age-related bone loss in men suggests that routine maintenance of adequate calcium and vitamin D intake, exercise, early recognition and treatment of testosterone deficiency, and modification of other osteoporotic risk factors may have prophylactic value. Future basic research on the cellular biology of bone in health and disease and clinical trials assessing the effects of long-term prophylactic and treatment regimens on bone mass and fracture occurrence will expand the understanding of osteoporosis in men. PMID- 2189056 TI - Evaluation and outcome of patients with syncope. AB - We studied 433 patients with syncope to derive insights into the diagnostic evaluation and outcome of patients with this common problem. This study shows that the etiology of syncope was not found in approximately 41% of patients. When a cause of syncope was determined, it was most frequently established on the basis of initial history, physical examination and an electrocardiogram (EKG). Furthermore, many of the other entities (e.g., aortic stenosis, subclavian steal) were suggested by findings on the history and physical examinations that required directed diagnostic testing. Initial EKG was abnormal in 50% of patients but led to a cause of syncope infrequently (less than 7%). Prolonged electrocardiographic monitoring, which has assumed a central role in the evaluation of syncope, led to a specific cause in only 22% of patients. Other tests were less often helpful in assigning a cause of syncope. At 5 years, the mortality of 50.5% in patients with a cardiac cause of syncope was significantly higher than the 30% mortality in patients with a noncardiac cause or 24.1% in patients with an unknown cause. At 5 years, a mortality of 50.5% in patients with a cardiac cause of syncope was noted. There were 54 actual deaths in this group as compared to 10.7 expected deaths based on 1980-86 mortality data from Allegheny County, PA (standardized mortality ratio = 5.02). At 5 years, a 33.1% incidence of sudden death was noted in patients with cardiac cause of syncope, as compared with 4.9% in patients with a noncardiac cause and 8.5% in patients with an unknown cause. Mortality and sudden death remained significant for the first 3 years after which the survival curves were parallel. A cardiac cause of syncope was an independent predictor of sudden death and mortality. Recurrences were common but were not associated with an increased risk of mortality or sudden death. Major vascular events were also more frequent in patients with cardiac causes of syncope. The results of this study will be helpful in designing future studies to evaluate the usefulness of newer diagnostic techniques. Furthermore, short- and long-term outcome data will be useful in planning intervention strategies in these patients. PMID- 2189057 TI - Rules: the new institutions. AB - Despite the pervasive philosophy of normalization and the more recent emphasis on "quality assurance," service provision in today's Medicaid-funded residential environment has become more regulation-oriented and less person-oriented. In this article, this argument was presented in the context of rule-governed versus contingency-shaped behavior of caregivers. The culpable process was identified as the coercive enforcement of inaccurate rules, which precludes responsive staff action and generates adverse consequences. The impenetrable system of rules was compared to the "old institutions," and solutions were advanced to bring staff members more in contact with the natural contingencies of teaching and caring. PMID- 2189058 TI - Regulating professional services in ICFs/MR: remembering the past and looking to the future. AB - Generally, our society regulates from a standpoint of failure in the system. When the field of mental retardation could not adequately monitor its own professional practices, litigation and legislation brought the onset of government intervention. Historically, consensus building has been the method by which standards emerge and then become adopted into regulation. Yet at best, this practice results in "opinions" as to how quality should be defined. The Health Care Financing Administration's experience in regulating and enforcing has resulted in an emphasis on the outcomes of services received by individuals. Though difficult, it challenges professionals to begin defining accountable measures of "quality" over time. PMID- 2189059 TI - Chemical characterization of lipopolysaccharides from Proteus strains used in Weil-Felix test. AB - The lipopolysaccharides (LPS) extracted from Proteus strains OX2, OX19, and OXK used as antigens in the Weil-Felix test, were characterized by chemical analysis and SDS-polyacrylamide gel electrophoresis (SDS-PAGE). To separate the O polysaccharide, core-oligosaccharide, and lipid A moieties, each LPS was treated with 2% acetic acid, centrifuged, and applied to Sephadex G-50 column. The core oligosaccharides contained L-glycero-D-mannoheptose, D-glycero-D-mannoheptose, glucose (Glc), galactose, 3-deoxy-D-mannooctulosonic acid, uronic acid, phosphate, glucosamine (GlcN), and galactosamine (GalN). The lipid A preparations contained GlcN, GlcN-phosphate, and three fatty acids (myristic, plamitic, and beta-hydroxymyristic acids). However, the O-polysaccharides of OX2- and OXK-LPS had different chemical compositions which consisted of Glc, GlcN, and quinovosamine, and Glc, uronic acid, and GalN, respectively, while OX19-LPS seemed to lack O-polysaccharide. PMID- 2189060 TI - Protective effect of recombinant human interleukin-2 against lethal infection caused by Klebsiella pneumoniae. AB - The effects of recombinant human interleukin-2 (rIL-2) administered prophylactically on the death of CBA/J mice challenged with Klebsiella pneumoniae 27 intraperitoneally were examined. rIL-2 administered subcutaneously at 20 micrograms per mouse for 7 days enhanced survival after a lethal challenge. The injection of anti-asialo GM1 antibody did not influence the effect of rIL-2. In mice given rIL-2, the number of peritoneal macrophages increased, and the infiltration of polymorphonuclear leukocytes (PMN) into the peritoneal cavity after the bacterial challenge was enhanced. In addition, adoptive transfer of sera and peritoneal exudate cells (PEC), consisting of an approximately equal number of macrophages and PMN, obtained from mice given rIL-2 enhanced resistance to a K. pneumoniae infection, compared with adoptive transfer of sera and PEC obtained from mice not given rIL-2. These results indicate that rIL-2 protects mice from a lethal challenge with K. pneumoniae, and suggest that the protective effect is due to an increase in the number of phagocytic cells and in the cooperative activity of the sera and the phagocytic cells. PMID- 2189061 TI - Arrest of DNA replication of macrophages in BCG granuloma and peritoneal exudates by bacteria. AB - Previously we found that bacterial surface substances induced the suppression of DNA synthesis of macrophages. We examined in the present study whether DNA synthesis of macrophages could be similarly suppressed by whole bacteria themselves. For this purpose we isolated macrophages from BCG granuloma of guinea pigs and rats. The macrophages from both of the animals gave essentially the same results. No isolated macrophages containing bacilli were found to incorporate 3H thymidine when tested by autoradiography. Further, DNA replication of peritoneal exudate macrophages was markedly and rapidly suppressed in vitro upon phagocytosis of various kinds of bacteria but not of non-bacterial preparations. A close correlation was found between granuloma formation and inhibition of 3H thymidine incorporation by MDP, its analogs, and various bacteria. These findings suggest that macrophages suppress their DNA replication when they phagocytose bacteria and that they can discriminate between bacteria and non-bacterial preparations. PMID- 2189062 TI - Abnormal protein translocation as the elusive cause of cystic fibrosis: an hypothesis. AB - Despite the recent rapid advances in isolation of the abnormal gene responsible for cystic fibrosis, there remains the need to explain the mechanism by which a single gene mutation causes the widespread clinical effects seen in this disease. Careful review of the otherwise unexplained abnormalities of cystic fibrosis from the perspective of cell biology reveals the following common features: (1) all these abnormalities involve proteins which are either (A) inserted into cell membranes in the RER and arrested after partial translocation or (B) inserted into RER membranes and fully translocated to be compartmentalized away from the cytosol in secretory vacuoles, lysosomes or peroxisomes; (2) all the involved proteins have minor abnormalities in their physicochemical properties or activity functions; (3) none of the involved proteins are missing or totally deficient in function; (4) final compartmentalization of the involved proteins is unaffected. These observations have directed our attention to the process by which most proteins are inserted into and translocated across lipid bilayer membranes, namely the signal peptide mechanism. This mechanism, not previously examined in cystic fibrosis, is reviewed in detail. Of the major proteins controlling signal peptide translocation, deficiencies in the function of signal peptidase activity appear most capable of causing the effects seen in cystic fibrosis. PMID- 2189063 TI - Suicide and the menstrual cycle. AB - A review of studies on the variation in suicidal behavior over the menstrual cycle identified only five studies with data presented in sufficient detail that they could be pooled, providing a sample of 400 menstruating women. A deficit in acts of attempted suicide in week three of the cycle was revealed, and it was suggested that this supports a hormonal explanation of the variation. PMID- 2189064 TI - Riley-Day syndrome, brain stimulation and the genetic engineering of a world without pain. AB - Riley-Day Syndrome, a genetic disorder in which there is impaired ability or inability to feel pain, hot and cold, is cited as an example of evidence that the commonplace notion that life cannot be painless is not necessarily valid. A hypothesis is presented to the effect that everything adaptive which is achievable with a mind capable of experiencing varying degrees of both pleasure and pain (the human condition as we know it) could be achieved with a mind capable of experiencing only varying degrees of pleasure. Two possible approaches whereby the human mind could be rendered painless are a schematically-outlined genetic approach, which would or will probably take thousands of years to implement, and a brain stimulation approach that could be effected by means of a noninvasive, contactless, transcranial, deep-neuroanatomic-site-focusable, electromagnetic and/or ultrasonic (and/or, conceivably, other kind of) brain pacemaker which could be developed within a few years. In order to expedite the relief of all kinds of suffering and the improvement of the human condition in general, it is advocated that prompt and concerted research effort be directed toward the development of such a brain pacemaker. PMID- 2189065 TI - Cell membrane activities and regeneration mechanisms as therapy mediators in moxibustion and acupuncture treatments: theoretical considerations. AB - Needling by acupuncture or heating by moxibustion, the major Chinese medicine modalities, include tissue destruction or increased permeability of cell membrane. Both action potential activities and the release of cellular metabolites responsible for regeneration occurs. These phenomena are eventually abolished by local and systemic inhibitory elements being metabolites or neurogenic. The inhibitory effect induced by the acupuncture and moxibustion and directed to the manipulation site of these modalities may affect other anatomical sites and reduce or prevent neoplastic growth and neuromuscular or cardiac membrane activity disturbances. PMID- 2189066 TI - Effect of Escherichia coli lipopolysaccharide on phosphatidylcholine biosynthesis by rat lung and alveolar type II cells. AB - Alterations in pulmonary surfactant are partly responsible for the respiratory insufficiency seen under septic shock process. We have used an experimental model of LPS-induced shock in rats to examine the cells responsible for the pulmonary surfactant synthesis and its relationship to lung injury. (14C)Choline incorporation into phosphatidylcholine was significantly reduced in lung homogenates or type II cells obtained from LPS-treated animals. Addition of LPS in vitro fails to increase (14C)choline incorporation in type II cells obtained from LPS-treated animals. We suggest that this depression of pulmonary phosphatidylcholine synthesis may partly explain the occurrence of respiratory failure with septic shock. PMID- 2189067 TI - Mutagenicity evaluation of HC Blue No. 1 and HC Blue No. 2. III. Effects in the Salmonella typhimurium/Escherichia coli reversion assay and the mouse lymphoma L5178Y TK+/- forward mutation assay. AB - The hair-dye ingredients, HC Blue No. 1 (HCB1) and HC Blue No. 2 (HCB2), were tested for the induction of bacterial mutation using Salmonella typhimurium strains TA1535, TA1537, TA98 and TA100; and Escherichia coli strains WP2uvrA-. In addition, both dyes were evaluated in the mouse lymphoma L5178Y TK+/- assay (MLA) for the potential to induce forward mutation. A liver homogenate (S9) prepared from Aroclor 1254-induced male Fischer 344 rats was used to provide a means for metabolic activation. HCB1 was not mutagenic in the Ames assay, but was weakly mutagenic in the MLA only in the presence of metabolic activation. In contrast, HCB2 was a strong mutagen in the Ames assay in tester strain TA98 both in the presence and absence of metabolic activation. A positive response was also noted with HCB2 in the MLA, both in the presence and absence of metabolic activation. Negative findings from the Ames assay of this study agree with other published results where an identical lot of HCB1 was used. Using the same lot, a weak positive result was observed in the MLA, however, the activation requirements and magnitude of the response were different from that of a lot evaluated by the NTP. In contrast, HCB2 appears to be both a bacterial and mammalian cell mutagen independent of lot variability. PMID- 2189068 TI - Dystrophin is localized to the plasma membrane of human skeletal muscle fibers by electron-microscopic cytochemical study. AB - Electron-microscopic immunoperoxidase technique revealed plasmalemmal localization of dystrophin in microscopically normal human skeletal muscle fibers obtained from nine routine diagnostic muscle biopsies. There was no evidence of periodicity of the immunoreactive product nor was there any evidence of immunostaining in any organelle besides the plasma membrane. Dystrophin appears to be a cytoskeletal protein associated with the plasmalemma. Its function is presumed to be the maintenance of the mechanical stability of the surface membrane so that it can withstand the normal contraction-induced stresses without disruption. PMID- 2189069 TI - Fasciitis, perimyositis, myositis, polymyositis, and eosinophilia. AB - Several groups of cases of fasciitis and myositis with eosinophilia are reported. The common features are inflammation into fascia and/or perimysium, and/or muscle fibers; eosinophilia in blood and/or in muscle biopsy. The following classification of 24 cases is suggested: at one end of the spectrum are fasciitis with eosinophilia: diffuse fasciitis (Shulman syndrome): 10 cases (3 with hematological complications); 2 cases of diffuse fasciitis with muscle atrophy; 3 cases of restricted fasciitis. Relapsing perimyositis with eosinophilia belong to the same spectrum, either diffuse (5 cases) with myalgias, or localized (2 cases). Other cases are focal myositis or multiple myositis, polymyositis with eosinophilia. The relationship among these cases is discussed. There is a continuum among the different groups. The pathophysiology remains unknown. PMID- 2189070 TI - Inadvertent transmission of a donor's acute myeloid leukemia in bone marrow transplantation for chronic myelocytic leukemia. PMID- 2189071 TI - [The insulin receptor]. PMID- 2189072 TI - [The apnea syndrome in adults]. PMID- 2189073 TI - Diabetes mellitus, the renin-angiotensin system, and angiotensin-converting enzyme inhibition. AB - Many traditional antihypertensive drugs are linked to various effects that may cause concern in the hypertensive diabetic patient. The favorable tolerability of angiotensin-converting enzyme (ACE) inhibitors in essential hypertension makes it likely that they will be well tolerated when used in diabetic patients. Data from ongoing studies support the theory that ACE inhibitors lower blood pressure to the same extent in hypertensive diabetics as in patients with essential hypertension. ACE inhibitors do not seem to affect glucose homeostasis adversely; they may even improve glucose tolerance to a small degree. The renal effects of ACE inhibitors in animal experiments suggest a renal-protective effect that can make them especially valuable. PMID- 2189074 TI - Long-term renal effects of enalapril therapy in patients with renal insufficiency. AB - Angiotensin-converting enzyme inhibitory therapy is widely used to treat hypertension. With long-term use, it is now being shown to have a beneficial effect on renal function and proteinuria in patients with renal insufficiency. When hypertensive patients with renal insufficiency are treated with enalapril, glomerular filtration rate is maintained, effective renal plasma flow is increased, and microalbuminuria and gross proteinuria are reduced. These beneficial renal changes with enalapril therapy differ from those of most other conventional antihypertensive medications. Clinical awareness of potential problems with hyperkalemia and increasing azotemia, particularly in the setting of salt/volume depletion, is important to assure optimal patient management. When these problems occur, they are nearly always reversible by correcting salt/volume status and/or interrupting enalapril therapy. PMID- 2189075 TI - Evaluation of the effect-duration of once-daily enalapril compared with once daily captopril. AB - The extent and duration of the antihypertensive effect of enalapril and captopril, both given once daily, were evaluated in 12 mild-to-moderate essential hypertensives by 24-hour noninvasive blood pressure (BP) monitoring (Pressurometer IV-mod 1990-1991, Del Mar Avionics). Patients were randomized to a cross-over regimen either with enalapril, 10-20 mg, followed by captopril, 50-100 mg (first group), or with captopril followed by enalapril (second group). The dose was doubled if, at week 3 of each treatment, the diastolic BP remained at 90 mm Hg. Doubling of the 2 drugs was not required in 4 patients; in 7 patients the dose of both drugs was doubled; and in 1 patient the dose of only captopril was doubled. Two of the 7 patients who required doubling of both drugs were considered nonresponders to enalapril and captopril. The circadian rhythm was not altered by the treatments, and the drugs reduced BP mainly during the waking hours. However, the second peak of systolic BP in the late afternoon did not graphically appear to be modified by captopril administration. A periodic asymmetric model with 3 harmonics analysis carried out on 24-hour BP data justifies only the use of enalapril for once-daily administration. PMID- 2189076 TI - Beneficial effects of angiotensin-converting enzyme inhibitor on renal function and glucose homeostasis in diabetics with hypertension. AB - The antihypertensive efficacy of enalapril and its effects on renal function and glucose homeostasis were investigated in 9 hypertensive patients with non-insulin dependent diabetes mellitus. Enalapril therapy produced a significant fall in blood pressure (BP) (p less than 0.05) and a significant increase in renal blood flow (p less than 0.05) without a change in glomerular filtration rate. Furthermore, fasting plasma glucose was significantly reduced (p less than 0.01). Similarly, M value, as an index of plasma glucose control in diabetes, was significantly reduced from 19.6 to 10.1 (p less than 0.01). These findings suggested that the angiotensin-converting enzyme inhibitor enalapril was effective in reducing BP and improving renal function, and might improve glucose homeostasis in hypertensive diabetics. PMID- 2189077 TI - Enalapril in the long-term treatment of elderly hypertensives. AB - The long-term antihypertensive effects of enalapril were assessed for a period of up to 1 year in 44 elderly patients with mild-to-moderate essential hypertension. Following a 2-week placebo period, patients who were assigned to enalapril were followed for 6 weeks in a randomized clinical trial. In patients who benefited from enalapril, treatment was continued and subjects were followed for up to 1 year. Supine and standing systolic and diastolic blood pressures were significantly reduced throughout the 1-year period compared with baseline. The dosage of enalapril was increased from 10 to 20 mg daily in 12 patients; 8 required additional antihypertensive agents. Enalapril is effective in the long term treatment of hypertension; no loss of antihypertensive agents. Enalapril is effective in the long-term treatment of hypertension; no loss of antihypertensive effect occurs. PMID- 2189078 TI - Growth of carotid plaques. PMID- 2189079 TI - EEG frequency analysis. PMID- 2189080 TI - Critical analysis of the use of computer-assisted transverse axial tomography to study human brain in aging and dementia of the Alzheimer type. PMID- 2189081 TI - Clinical neuromythology. VIII. Upper and lower motor neuron: the little old synecdoche that works. PMID- 2189082 TI - Immunocytochemical localization of desmin at human neuromuscular junctions. AB - We localized desmin at human neuromuscular junctions (NMJs) using specific anti desmin monoclonal and polyclonal antibodies. It was highly concentrated in the postsynaptic domain. It was found in all the NMJs examined. Compared with the area of acetylcholine receptors identified by bound alpha-bungarotoxin, the strong desmin immunoreactivity occupied a slightly larger area and was localized slightly deeper in the muscle fiber, suggesting that desmin might be accumulated within the postsynaptic folds and possibly below the folds. This appears to be the first identification of a protein unrelated to cholinergic transmission accumulated at human NMJs. PMID- 2189083 TI - Paraneoplastic motor neuron disease and renal cell carcinoma: improvement after nephrectomy. AB - A 74-year-old man had a paraneoplastic motor neuron disease mimicking amyotrophic lateral sclerosis. He had an elevated erythrocyte sedimentation rate, other laboratory abnormalities, and a previously undiagnosed renal cell carcinoma. Four months after nephrectomy, his strength had improved and he had no fasciculations. Seven other patients with cancer and motor neuron disease improved or stabilized after tumor treatment. Even though it is rare, paraneoplastic motor neuron disease is important to diagnose because it may be treatable. PMID- 2189084 TI - Interrater variability with the Expanded Disability Status Scale (EDSS) and Functional Systems (FS) in a multiple sclerosis clinical trial. The Canadian Cooperation MS Study Group. AB - We describe the interrater variability in the Expanded Disability Status Scale (EDSS) and Functional Systems (FS) in a multiple sclerosis clinical trial. Two physicians blinded to their previous assessments and to each other's scores consecutively examined 168 patients (545 paired examinations). Perfect agreement on the assignment of the disability scores ranged from 48% (cerebellar functional group) to 69% (EDSS and pyramidal functional group). Only 31% to 62% of this agreement occurred independently of that expected by chance (kappa). With the exception of the cerebellar and sensory functional groups, agreement within 1 step occurred in at least 92% of cases. These findings suggest that differences of a single step on these scales may not reflect an important functional change. We recommend that at least a 2-step change (1.0 point on the EDSS and 2 points on the FS) is needed to be confident of an important change in the degree of disability or response to treatment in this disease. PMID- 2189085 TI - Hemodynamic changes after ruthenium irradiation of Hippel's angiomatosis. AB - The authors report a case of Hippel's angiomatosis successfully treated with contact beta irradiation. The area of the multiplex retinal angioma and the accompanying retinal detachment was irradiated with a 106Ru/106Rh radioactive applicator. Hemodynamic changes due to irradiation were followed up in the ipsilateral ophthalmic artery with transcranial Doppler sonography. Scarring was also demonstrated by fluorescein angiography and A- and B-scan ultrasonography. Irradiation caused the narrowing and later the occlusion of the precapillaries and capillaries (i.e. the resistance vessels) and that of the shunts inside the angioma; consequently, vascular resistance increased. Transcranial Doppler sonographic recordings showed a decrease in blood flow velocity as compared to pathologically increased blood flow velocity in angiomas, and a gradual increase in vascular resistance which was lower before treatment. PMID- 2189086 TI - [Experience with 1000 cases of conization of the uterine cervix]. AB - Authors made a follow-up study of 1000 portio conisations. They analysed the early and late postoperative complications with special regard to the further obstetrical outcome. They valued the previous cytologic and colposcopic examinations on the basis of histologic diagnosis. It has been found that complications were neither frequent nor serious and had no unfavourable influence on further pregnancies. They found a higher ratio both of false positive and negative cytologic and colposcopic results then it is given by the literature. Authors come to the conclusion, that even in cases of anatomical portio alterations it's necessary the detailed histologic examinations, that for the portio conisation is a preferable method. PMID- 2189087 TI - [Examination of the diastolic function of the left ventricle by Doppler echocardiography in coronary disease]. AB - The authors examined the left ventricular diastolic function at rest and in pain free period in patients with chest pain but without previous myocardial infarction. Two patient group were formed according to the results of coronarography: 15 patients had significant coronary artery stenosis, while the coronarography was negative in case of 11 patients. Four Doppler echocardiographic parameters were taken and their sensitivity, specificity, positive and negative predictive values were determined on the base of the result of the coronarography. The small number of patients allows only preliminary evaluation but the results suggest that the altered diastolic function enhances the probability of the presence of significant coronary artery disease, while a normal diastolic function decreases its probability. PMID- 2189088 TI - [Non-invasive determination of the hemodynamic significance of vasoconstriction: study of the arteria femoris profunda using ultrasound]. AB - In case of occlusion of the superficial femoral artery (SFA), the profunda femoris artery (PFA) supplies the entire lower extremity. Not infrequently the SFA occlusion is associated with stenosis of the origin of the PFA. The angiographic study of the origin of PFA is often unsatisfactory. The purpose of the present study was to develop objective criteria for the diagnosis of the PFA origin stenosis by duplex scanning. In 60 patients, we examined 75 femoral bifurcations by duplex scanning and compared them with the independently performed angiography. Group I. (n = 20 PFA origins) consisted of 10 normal individuals. Group II. (n = 30 PFA origins) consisted of 25 patients with angiographically proven SFA occlusion and normal PFA. Group III. (n = 25 PFA origins) consisted of 25 patients with angiographically proven SFA occlusion and PFA orifice stenosis. We measured the maximal systolic and mean flow velocity in the orifice of the PFA at rest and during the maximal hyperemia following 3 min of ischemia of the lower leg. At rest, the maximal flow velocity in the groups I III. was 60 +/- 15, 142 +/- 44 and 255 +/- 60 cm/s (p less than 0.01) and the mean flow velocity was 8 +/- 6, 32 +/- 9 and 96 +/- 42 cm/s (p less than 0.01). During hyperemia, the maximal and mean flow velocity for the groups I-III. was 59 +/- 15, 155 +/- 42 and 286 +/- 82 cm/s (p less than 0.01) and 8 +/- 5, 55 +/- 19 and 144 +/- 51 cm/s (p less than 0.01), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189089 TI - [Laszlo Nemeth, a school physician]. PMID- 2189090 TI - [Cases of unusual deaths in the registry of Hont County in the years 1750-1759]. PMID- 2189091 TI - [Additional data on the history of thoracic surgery at the Institute for Pulmonary Diseases in Debrecen]. PMID- 2189092 TI - [DNA-based diagnosis]. AB - DNA diagnostics is rapidly developing and gaining ground especially in the identification of genetic, malignant and infectious diseases as well as in the identification of individuals by means of DNA finger-printing. Present review deals with these and with the technical aspects of DNA diagnostics. The rapidly expanding field of diagnostics is contrasted by gene therapy which is recently not yet adaptable for human use. PMID- 2189093 TI - [Immunohistochemical studies in contaminated small bowel syndrome]. AB - This study was undertaken to evaluate the number of the immunoglobulin producing cells in the lamina propria of the small intestine by immunocytochemical techniques, using peroxidase-antiperoxidase (PAP) complex in normacid patients with CSBS. 25 patients were studied including 13 patients with bacterial overgrowth, where the bacterial concentration was higher than 10(4) colony forming units/ml, and 12 subjects with normal bacterial concentration, served as control. The patients with CSBS were treated with antibiotics according to the antibiotic resistance. After treatment the luminal bacterial concentrations was lower than 10(4) cfu/ml in 7 of 13 patients (CSBS I. group). In 6 patients the bacterial concentration remained high (CSBS II. group). The immunoglobulin producing cells were determined in biopsy specimens taken from the lower part of duodenum. The number of the IgA and IgM producing immunocytes was significantly decreased only in the CSBS II. group. Our results show that temporary immunological alterations may play an important role in the mechanism of the recurrent CSBS. PMID- 2189094 TI - [Epidemiology of germinal cell testicular tumor in Hungary]. AB - The data of 1286 testis cancer persons were analyzed by the authors, which were identified in Hungary between 1981 and 1986. The comparison was carried out with international findings in this field. The incidence rate of testis tumor in Hungary reaches a value of 4.16/100,000 men/year, which seems to be quite near to the frequency of cases occurred in Northern-Europe. The patient's age was 32.9 year in the mean at the time of the diagnosis, and the age-specific incidence rate was the highest (11.2) between 25-34 years, according to international experiences. A significant difference was found in the frequency of testis cancer among 19 counties of Hungary. The extremely high testis cancer incidence in the county Vas (West-Hungary) requires further explanations. A seasonal pattern according to the patients birth months was shown, which did not correlate with data of other Hungarian authors concerning seasonal pattern of the undescendent testis. PMID- 2189095 TI - [Hippocrates--2450 years old]. PMID- 2189096 TI - [The Fischhof brothers]. PMID- 2189097 TI - [Experience with the surgical treatment of lung cancer in young adults]. AB - There was found 287 patients (7.3%) under 45 years among 3911 operated primary lung cancer between 1970-1980. 36.9% of the diseases was discovered by x-ray screening, 63.1% by complaints. The operability of the patients in the first 3 months (55.8%) after discovery was 81.25% versus 63% later than 3 months. There were distributed by histology 34.1% squamous cell, 31% adenocarcinoma, 31.4% small cell and 3.5% large cell lung cancer. According to the stages there were 17.4% Stage I, 3.5% Stage II, 79.1% Stage III. In the first two stages were the operability rate 100%, in Stage III. 66.1%. There were resected 210 patients (73.2%), and 127 were performed standard, 83 extended resections. The 30-day operative mortality was 5.9%. The 5-year survival time was 26.5% of all patients, 36.2% of resected patients. The rates of 5-year survival showed 39.8% with squamous cell, 22.5% with adenocarcinoma and 13.3% with small cell lung cancer. The author compares the own results to literature, expresses his opinion and standpoint of surgical possibilities for patients with lung cancer under 45. PMID- 2189098 TI - [Incidence and role of hypertension in the development and recurrence of acute myocardial infarct in a 5-year case load]. AB - Authors treated and checked 474 patients with acute myocardial infarction (AMI) during 5 years. The occurrence of hypertension was 37.15% of the total number of patients but this rate was 51.37% for women patients. Obesity, hyperlipidaemia and diabetes mellitus were the most frequent of the risk factors on the patients with hypertension. Asthma cardiale and acute arrhythmias were slightly more frequent early complications and cardial decompensation was a slightly more frequent late complication. The number of myocardial reinfarctions was the same both in the case of hypertensive and normotensive patients under the circumstances of parallel normalization and keeping the tension and serum cholesterol on the normal level. PMID- 2189099 TI - [In memory of Laszlo Detre (1874-1939), who coined the term "antigen"]. PMID- 2189100 TI - [Medical thinking in the era of imperial Rome]. PMID- 2189101 TI - Mutational analysis of v-rel, the oncogene of reticuloendotheliosis virus strain T. AB - Reticuloendotheliosis virus strain T (Rev-T) is a highly oncogenic retrovirus that induces a lethal lymphoma in young galliform birds and also transforms and immortalizes avian lymphoid cells in vitro. Rev-T presumably arose when a reticuloendotheliosis virus (Rev) incorporated a portion of the turkey c-rel gene into its genome, forming the v-rel oncogene. The predicted v-rel protein (p59v rel) has 14 amino acid substitutions and 3 amino acid deletions relative to the predicted turkey c-rel protein. The 5' Rev env-derived amino-terminus of p59v-rel also has amino acid substitutions in codons 3, 6, and 9 relative to wild-type Rev A env. To distinguish the critical alterations from the neutral ones, we made a mutation that resulted in a substitution of the 5' Rev env-derived amino-terminus by a single methionine, as well as several back-mutations, in the context of an otherwise wild-type v-rel and tested the transforming, immortalizing, and tumorigenic properties of the resulting proteins. All proteins tested retained the transforming, immortalizing, and tumorigenic functions of v-rel. Absence of the 5' Rev env-derived amino-terminus, as well as back-mutations of six of the amino acid changes present in the rel-derived amino-terminal and central regions of v-rel, reduced transformation efficiency. The mutations present in codons 3, 6, and 9 of p59v-rel showed complicated interactions in their activating effects on transformation efficiency. We also showed that loss of the immortalizing function did not abolish tumorigenesis by v-rel. We further showed that the primary transduction event involving the turkey c-rel gene could have occurred with a replication-competent Rev having v-rel-specific mutations in codons 3, 6, and 9 of the env gene. PMID- 2189102 TI - Transcriptional activation by human c-myb and v-myb genes. AB - The human c-myb proto-oncogene is the cellular progenitor of the viral v-myb oncogene and codes for a 75 kD protein involved in growth regulation and differentiation in a number of cells. Fusion proteins in which human c-myb sequences are linked to the DNA binding domain of the yeast transcriptional activator GAL4 can activate transcription from a reporter gene which carries the chloramphenicol acetyl transferase (CAT) gene linked in cis to a repeat of the GAL4 binding site. Deletions of carboxyterminal sequences allowed the identification of the domain responsible for transcriptional activation, which is located between amino acid residues 275 to 327. Deletion of this activator domain results in abrogation of the transcriptional activation. The GAL4-v-myb fusion protein can also activate transcription whereas no transactivation by GAL4-c-myb is observed, indicating that a carboxyterminal domain of c-myb which is absent from v-myb apparently negatively regulates transcriptional activation. Dimer formation which is required for transactivation by GAL4 fusion proteins can, when GAL4 is truncated, be mediated by a region of the c-myb protein upstream of the transactivator domain possibly including the transactivator domain itself but not a putative leucine zipper located downstream of this region. PMID- 2189103 TI - Identification and characterisation of the egr-1 gene product as an inducible, short-lived, nuclear phosphoprotein. AB - The egr-1 gene (also termed NGFI-A, zif/268 and Krox24) is predicted to encode a protein with three 'zinc finger' domains. Analogous DNA-binding motifs are present in several putative transcriptional regulatory proteins. The mRNA of egr 1 is rapidly and transiently induced by a variety of growth factors in diverse cell types. We have used a synthetic peptide corresponding to the C-terminus of the predicted egr-1 protein to generate mouse and rabbit polyclonal antibodies. These antibodies have been used to identify the egr-1 protein, designated p75egr 1, by immunoprecipitation, immunoblotting and immunocytochemical analyses. p75egr 1 is induced within 1-2 h of mitogenic stimulation and has a half-life of under 2 h. The protein is phosphorylated and has been localised to the nucleus by both immunocytochemical analysis and biochemical fractionation. The egr-1 protein is released from nuclei under isotonic or hypertonic salt conditions or by treatment with DNAase and binds double-stranded DNA in vitro. Consistent with the distribution described for the mRNA the egr-1 protein is abundantly expressed in normal rat brain. PMID- 2189105 TI - The leucine zipper domain of avian cMyc is required for transformation and autoregulation. AB - Small deletions of 7 to 48 amino acids have been generated in the leucine zipper domain of the avian cMyc protein and the mutant cMyc proteins expressed using an avian retroviral vector. Retrovirally encoded cMyc protein transforms primary chick embryo fibroblasts and leads to abnormal regulation of the endogenous c-myc gene. Deletion of the most C-terminal leucine of the zipper motif confers a partial phenotype affecting some but not all parameters of transformation. Complete loss of transforming activity results from deletion of further leucine residues, including one which is not part of the heptad repeat. In cMyc transformed cells endogenous c-myc mRNA is expressed at a low level and is abnormally refractory to induction by serum stimulation. In contrast, a non transforming cMyc protein which lacks the zipper does not affect normal c-myc expression. These results demonstrate that the leucine zipper domain of avian cMyc is required for both transformation and autoregulation, and suggests that essential leucine residues within the motif may be spaced differently from those in the zippers of Fos and Jun. PMID- 2189104 TI - Isoforms of the human ets-1 protein: generation by alternative splicing and differential phosphorylation. AB - The ets-1 gene belongs to the ets gene family (ets-1, ets-2, erg, and elk) and is homologous to the v-ets oncogene found in the avian leukemia virus E26. The ets-1 gene products were characterized using a specific monoclonal antibody developed against a bacterially expressed v-ets protein. The ets-1 gene product in the human T-cell line CEM was found to consist of at least six species: four major species with apparent molecular weights of 51 kDa (p51), 48 kDa (p48), 42 kDa (p42), and 39 kDa (p39); and two minor species of 52 kDa (pp52) and 49 kDa (pp49), which are demonstrated to be the phosphorylated forms of p51 and p48, respectively. All of the ets-1 proteins are related to each other and are considered products of the ets-1 gene. Subcellular localization showed that the pp52 and p51 are found mainly in the cytoplasm, while p48 and p39 are found mainly in the nucleus. Specific antibodies against various exons of ets-1 showed that both p42 and p39 lack a region corresponding to exon VII. Polymerase chain reaction analyses revealed the presence of an additional RNA product that corresponds to mRNA lacking exon VII. These results suggest that the human ets-1 gene encodes multiple proteins that are generated by at least two distinct mechanisms: alternative splicing of mRNA and protein phosphorylation. PMID- 2189106 TI - Demonstration by in situ hybridization of ret proto-oncogene mRNA in developing placenta during mid-term of rat gestation. AB - Expression of the ret proto-oncogene (proto-ret) in rat conceptus tissues during development was examined by in situ hybridization using photobiotin-labeled oligodeoxyribonucleic acid probes corresponding to regions coding for the kinase and transmembrane domains of proto-ret gene product. High levels of the proto-ret transcripts were detected in the cytotrophoblasts in the placenta in the mid gestational period (days 10 and 11), but on day 14 of gestation, when the placenta was undergoing morphological changes, transcripts could no longer be detected in the trophoblasts. These results suggest that the increased expression of proto-ret may be associated with the proliferation and/or differentiation of trophoblast cells at a specific stage. Improvements in the in situ hybridization technique by introduction of an ultrafast microwave energy fixation method, and repeated-reaction cycling of avidin-alkaline phosphatase and a biotinylated anti avidin antibody for signal amplification, are also briefly discussed. PMID- 2189107 TI - A 3' truncation of MYC caused by chromosomal translocation in a human T-cell leukemia increases mRNA stability. AB - The proto-oncogene MYC is rearranged at its 3' end in the human T-cell leukemia line Hut 78 as a result of a translocation between the long arms of chromosomes 8 and 2. The nucleotide sequence at the breakpoint shows that the rearranged allele of MYC is truncated 24 nucleotides before the first poly(A)-addition signal. The 3' truncated MYC lacks a 61 nucleotide AT-rich sequence that has been reported to mediate selective mRNA degradation. We show that the truncation results in prolonged stability of MYC mRNA: the half life of the MYC mRNA in Hut 78, as well as in Rat 1A cells transfected with the truncated allele of MYC is increased by at least 5-fold. Our results document yet another mechanism by which MYC may be rendered pathogenic and dramatize the importance of mRNA stability in the regulation of MYC activity. PMID- 2189108 TI - Lack of correlation between intercellular junctional communication, p21rasEJ expression, and spontaneous metastatic properties of rat mammary cells after transfection with c-H-rasEJ or neo genes. AB - The loss of intercellular junctional communication between rat 13762NF mammary carcinoma cells and their spontaneous metastatic potentials from the mammary fat pad show a high degree of correlation. We examined a stable, benign, completely junctionally coupled cell clone (MTC.4) of this system after calcium phosphate mediated transfection with c-H-rasEJ/pSV2neo and control pSV2neo-containing plasmids. There was a good correlation between the copy numbers of c-H-rasEJ incorporated into MTC.4 cells and their contents of p21rasEJ; however, there was not always a correspondence between spontaneous metastatic potential and copy number of c-H-rasEJ or amount of p21rasEJ. After c-H-rasEJ/pSV2neo transfection, some MTC.4 cells lost intercellular junctional communication and became spontaneously metastatic, although some nonmetastatic transfectants also had low percentages of junctionally coupled cells. One of the control pSV2neo transfectants also became metastatic and lost intercellular junctional coupling, and calcium phosphate treatment itself resulted in increased growth rates at mammary fat pad sites and a marginal increase in incidence of spontaneous metastases, both of which preceded loss of intercellular junctional coupling in some cells. Examination of 12 subclones derived from two cloned transfectants, however, revealed a poor correlation between spontaneous metastatic potential and intercellular junctional coupling. The results suggest that loss of junctional communication between cells is often but not always associated with the progression of cells from benign to metastatic states. PMID- 2189109 TI - K-ras oncogene expression in Xenopus laevis. AB - A Xenopus laevis homolog of mammalian Kirsten-ras has been isolated from an oocyte cDNA library. This ras clone has been used to examine the genomic representation and expression of ras in oocytes and embryos. The Xenopus homolog of K-ras is a low-copy gene encoding a 2.6 kb mRNA, which is present throughout oogenesis and embryonic development. DNA sequence analysis indicates that Xenopus and mammalian K-ras 2B are highly conserved at the mRNA level (82%) and encode nearly identical proteins. It should now be feasible to address the function of endogenous ras oncogene in the well-characterized Xenopus developmental system. PMID- 2189110 TI - A member of the ras gene superfamily is expressed specifically in T, B and myeloid hemopoietic cells. AB - A 1.26 kb murine cDNA having 31% homology with human ras and 55% homology with human rho proteins was isolated using an oligonucleotide probe homologous to catalytic subdomain of a tyrosine kinase subfamily. Northern blot analysis indicates that the expression of the murine gene is restricted to the cells of hemopoietic lineages and the mRNA levels increase with the terminal differentiation of hemopoietic cells into granulocytes. PMID- 2189111 TI - Bluemle era leaves mark at Jefferson. PMID- 2189112 TI - Expression of hybrid malaria antigens in insect cells and their engineering for correct folding and secretion. AB - Hybrid proteins containing selected regions of the major surface antigens of the sporozoite and merozoite stages of Plasmodium falciparum were expressed in insect cells using baculovirus vectors. A recombinant protein containing the signal peptide from the precursor to the major merozoite surface antigens (PMMSA) fused to a fragment from the carboxy (C) terminus of the same gene was recognized by monoclonal antibodies specific for reduction-sensitive conformational epitopes within the C-terminal fragment, suggesting that correct disulphide cross-linking of cysteine residues within this region had occurred. Addition of 26 copies of the tetrapeptide repeat from the circumsporozoite protein (CSP) resulted in a protein recognized by anti-CSP antiserum as well as the conformation specific monoclonal antibodies. Deletion of the C-terminal putative anchor sequence from both proteins resulted in secretion of protein in a fully soluble form antigenically indistinguishable from the anchor containing products. Correct conformation was not observed when the proteins were expressed as polyhedrin fusions without the signal peptide. These data indicate that the PMMSA signal peptide is recognized in insect cells and that correct assembly of disulphide cross-links is dependent upon targeting the protein to the endoplasmic reticulum. PMID- 2189113 TI - The effect of Plasmodium falciparum exo-antigens on the morphology of uninfected erythrocytes. AB - It was observed that uninfected red cells resuspended in supernatant from Plasmodium falciparum cultures, then examined between a glass slide and cover slip, assumed varying morphologies. A series of experiments suggested that P. falciparum releases molecules which cause red cells to become stomatocytic (cupped). These molecules, some of which are heat-stable have an apparent molecular weight greater than 12 kDa, are released at or about schizogony, and do not bind tightly to erythrocytes. PMID- 2189114 TI - Commitment of the malaria parasite Plasmodium falciparum to sexual and asexual development. AB - Blood-stage malaria parasites in the vertebrate host can develop either into the asexual, multiplying forms, called schizonts, or into gametocytes, the sexual stages of the parasite. In the present work we studied the differentiation into asexual parasites or gametocytes of the progeny of single, isolated schizonts of the clone 3D7A of Plasmodium falciparum, using monoclonal antibodies specific for the sexual or asexual stages of the parasite. We observed that schizonts obtained from a continuous culture undergoing serial cycles of growth and dilution with fresh red blood cells produced either only gametocytes or only asexual parasites, showing a high degree of commitment to one or the other developmental pathway. The relative proportion of schizonts which produced gametocytes was very low at low parasite densities in culture, while at high parasite densities a much greater proportion of schizonts produced gametocytes. Nevertheless, at both low and high parasite densities individual schizonts were almost always fully committed to producing only gametocytes or only asexual parasites. PMID- 2189115 TI - Glutathione transferase in helminths. AB - The helminth glutathione (GSH) transferases are present as isoenzymes but fail to show a clear biochemical homology to any of the three mammalian GSH transferase families. GSH transferase is one of the major detoxification systems found in helminths, particularly high levels being found in cestodes and digeneans. Helminth GSH transferases bind a range of anthelmintics but there is limited evidence that the enzymes can conjugate anthelmintics with glutathione. Other natural substrates of helminth GSH transferase may be secondary products of lipid peroxidation including lipid hydroperoxides and reactive carbonyls. Lipid peroxidation can arise via free radicals produced by host immuno-effector cells and helminth GSH transferase may help form a defence system against immune mediated damage. GSH transferase has also been identified as a protective antigen in schistosomiasis. PMID- 2189116 TI - Strabismus. AB - Patients with strabismus should be viewed as having a serious ocular disorder requiring early diagnosis and evaluation. They should also be encouraged to have proper therapy so that they may be returned to a more normal ocular status at the earliest possible age. The ultimate goal of the pediatric ophthalmologist is always good vision and proper alignment. Neither alone is acceptable. The pediatric practitioner should diagnose strabismus disorders at the earliest possible age so that full and proper treatment may be brought to bear, thus allowing the patient to enjoy binocular vision function throughout life. PMID- 2189117 TI - Amblyopia and the pediatrician. AB - Amblyopia is one of the most common and significant eye ailments in children. It is classified into organic and functional; functional is further divided into classifications of deprivation, strabismic, and refractive. Early diagnosis and treatment are of paramount importance. Diagnostic techniques are age-related. Treatment consists of eliminating associated defects, properly focusing the image on the retina (glasses or contact lens), and patching the good eye to force the child to use the amblyopic eye. Treatment may only be effective within the first 2 or 3 months of life for some conditions and later in childhood for other conditions. Amblyopia can recur up to age 9. The pediatrician has the heavy responsibility of recognizing amblyopia at an early enough age to allow for effective treatment. Nationwide there are many pediatric ophthalmologists available to institute this early, effective treatment. With this teamwork, we can help eliminate the most common cause of visual impairment in the pediatric patient. PMID- 2189118 TI - Oculoplastic update. AB - Lacrimal tearing problems can be handled using a conservative approach by massage, antibiotic eye drops, nasal saline drops, and good hygienic care of the periorbital region. Cases in which preseptal inflammatory changes or marked exudated debris occur require early surgical intervention. Benign eyelid lesions can be identified in the majority of cases by clinical appearance. Many can be easily excised and left to heal by secondary granulation. Newer laser approaches can decrease pain, swelling and postoperative healing time. PMID- 2189119 TI - Inherited and developmental corneal disorders. AB - The cornea is one of the rare transparent tissues in nature. Its clarity and curvature are essential for clear and precise vision. This clarity may be adversely affected by a number of congenital and developmental conditions. It is important to recognize these defects early in order to prevent amblyopia, and, in many cases, to rule out congenital glaucoma or associated congenital or developmental disorders. Early treatment of corneal disorders may prevent permanent visual loss and can facilitate early visual rehabilitation. PMID- 2189120 TI - Visual correlates of dyslexia and related learning disabilities. PMID- 2189121 TI - Regulation of hematopoiesis. PMID- 2189122 TI - Effects of carotenoids on aflatoxin B1-induced mutagenesis in S. typhimurium TA 100 and TA 98. AB - The effects of beta-carotene, canthaxanthin, and extracts of tomato paste (containing lycopene) and orange juice (containing cryptoxanthin) on aflatoxin B1 (AFB1)-induced mutagenesis in S. typhimurium TA 100 and TA 98 were investigated. Inhibition of mutagenesis was studied during and following completion of AFB1 metabolism (i.e., after the addition of menadione), thereby permitting separate examination of the metabolic activation and phenotypic expression phases. Each experimental carotenoid, except lycopene, inhibited AFB1-induced mutagenesis in both tester strains. Cryptoxanthin was the most potent inhibitor, being at least an order of magnitude more potent than the other carotenoids. Inhibition by beta carotene and canthaxanthin was more prominent during the activation phase, whereas cryptoxanthin was more effective during the subsequent phenotypic expression phase. These inhibitory effects were not dependent on conversion to retinol. PMID- 2189123 TI - Effects of chronic beta-carotene supplementation on vitamin K status in adults. AB - Plasma vitamin K concentrations and prothrombin coagulation activity were determined in 26 normal adults who had received daily beta-carotene supplementation (0, 15, 30, or 60 mg) for six months. Neither plasma vitamin K nor coagulation activity were significantly decreased at any supplementation level. Thus, chronic beta-carotene supplementation, even at high daily doses, is not expected to result in clinical vitamin K deficiency. The data suggest separate mechanisms for intestinal absorption of beta-carotene and vitamin K. PMID- 2189125 TI - Ciprofloxacin. Best use of this new broad-spectrum antibiotic. AB - Resistance to traditional antibiotics is an increasing problem. The introduction of ciprofloxacin (Cipro) has been welcome, because it is safe and effective against many organisms (including drug-resistant ones), can be taken orally, and is well tolerated. Dr Fass provides a complete description of the drug, including its use for infections of the urinary, respiratory, and gastrointestinal tracts; skin and skin structures; and bones and joints. PMID- 2189124 TI - Review of patients' responses to epoetin alfa therapy. AB - The efficacy of epoetin alfa (recombinant human erythropoietin) has been tested for treating the anemia associated with end-stage renal disease. This anemia is caused by severely decreased levels of erythropoietin, 90% of which is ordinarily produced by healthy kidneys. Treatment with epoetin alfa successfully corrected the anemia of 97% of 333 patients, as evidenced by hematocrit levels that increased by at least 6 percentage points or reached a study target level of 35%, 2 points above current guidelines. The 127 patients who previously required red cell transfusions to maintain an adequate hematocrit became completely transfusion independent after receiving epoetin alfa. Furthermore, treatment with this growth factor alleviated many of the symptoms of uremia, such as loss of energy and appetite. The major side effect observed with epoetin alfa treatment was increased diastolic blood pressure; however, this was well controlled by additional antihypertension medication. There have been no reports of antibody formation in response to this drug. Thus, epoetin alfa is a safe and effective means of treating the anemia caused by chronic renal insufficiency. PMID- 2189126 TI - Using lipid-lowering agents effectively. When diet is not enough. AB - Lipid-lowering agents can be used safely and effectively if the physician understands the nature of the patient's disorder and the mechanism of action of the various drugs. The benefits of altering lipid levels are manifested over years, not months. Without a long-term plan for periodic follow-up and intervention, short-term gains will accomplish very little. PMID- 2189127 TI - Open-chest cardiac massage. The possible rebirth of an old procedure. AB - Open-chest cardiac massage was widely and successfully used for many decades before its virtual abandonment 25 years ago. Both experimental evidence and basic physiologic evidence indicate that it has many advantages over closed-chest massage (especially increased cardiac output). Both resuscitation techniques have specific and unique advantages and disadvantages: They are not mutually exclusive. However, significant increases in rates of survival after cardiac arrest cannot be expected with variations of closed-chest cardiac massage and standard advanced life support services. Therefore, physicians must be willing to support controlled human studies that can definitively determine the proper role of each in resuscitation after cardiac arrest. PMID- 2189128 TI - Sympathetic dystrophies. Recognizing and managing a puzzling group of syndromes. AB - The sympathetic dystrophies are poorly understood and underdiagnosed, especially in their milder forms. Although the two major syndromes, causalgia and reflex sympathetic dystrophy, are similar in many aspects, significant differences remain in clinical presentation, pathogenesis, and management. This discussion of these syndromes focuses on clinical presentation and diagnosis for the primary care physician. PMID- 2189129 TI - Sunlight, sunburn, and sunscreens. Preventing and remedying problems from 'too much fun in the sun'. AB - Exposure to ultraviolet (UV) radiation is a dose-related risk factor for the development of several cutaneous cancers. This risk is reduced by avoiding exposure to the sun and by the use of sunscreens. The latter products are rated according to their ability to protect skin from developing erythema. Treatment of overexposure is geared to relief of symptoms. Preventive measures, however, should always be encouraged. PMID- 2189130 TI - [Diseases of mediastinal organs (a lecture)]. PMID- 2189131 TI - [Early reaction to an agent causing pulmonary infections]. PMID- 2189133 TI - Erythropoietin therapy in autologous blood donors. PMID- 2189132 TI - Biology of hematopoiesis and synergy amongst hematopoietic growth factors. PMID- 2189134 TI - Erythropoietin therapy in AIDS. PMID- 2189135 TI - The use of recombinant human granulocyte-macrophage colony-stimulating factor in autologous bone marrow transplantation. PMID- 2189136 TI - Cellular interaction regulating the production of colony-stimulating factors. PMID- 2189137 TI - Effects of recombinant human granulocyte-macrophage colony-stimulating factor as treatment for aplastic anemia and agranulocytosis. PMID- 2189138 TI - Granulocyte macrophage colony stimulating factor (GM-CSF) in AIDS. AB - Overall GM-CSF is a well tolerated intervention in patients with HIV associated disease. As in a number of other clinical settings, it is able to improve myelopoiesis and abrogate the myelotoxicity of chemotherapeutic agents. At present, clinical data is insufficient to indicate an ultimate clinical benefit from the use of GM-CSF in terms of opportunistic infection, mortality or quality of life for HIV infected patients. As phase I and phase II trials are completed however comparative clinical trials addressing these issues are anticipated. Hematopoietic growth factors may permit the use of optimal doses of therapeutics and thereby play an adjunctive role in the combination therapies anticipated for the treatment of HIV related disease. PMID- 2189139 TI - Human granulocyte-macrophage colony-stimulating factor (GM-CSF): regulation of expression. AB - GM-CSF is a potent hematopoietic growth factor which exerts its effects on hematopoietic cell growth both in vivo and in vitro. In addition, GM-CSF has profound effects enhancing the functional activity of circulating effector cells. GM-CSF can be produced by a variety of cell types in response to immune stimuli; both T-cells and macrophages produce GM-CSF upon activation. Furthermore, activated macrophages secrete IL-1 and TNF, which can stimulate GM-CSF production by certain types of endothelial and fibroblast cells. This local production of GM CSF could then act on circulating neutrophils, monocytes and eosinophils to enhance their functions in host defense. Thus, one can envision a paracrine system in which the production of GM-CSF is sensitive to immune stimulation, and as a result of GM-CSF production, effector cells are recruited and their activities enhanced (Figure 4). The role of GM-CSF and other CSFs and interleukins in the homeostatic control of hematopoiesis is the subject of intense investigation. Careful integration of molecular and biological studies should yield exciting new information about both the physiologic and therapeutic roles of GM-CSF. PMID- 2189140 TI - Macrophage growth and stimulating factor, M-CSF. PMID- 2189141 TI - Interleukin-7: a new hematopoietic growth factor. AB - IL-7 is a regulator of early lymphoid progenitors of both the T cell and B cell lineages. The high level of expression of IL-7 mRNA under steady state conditions in the thymus suggest that IL-7 is an important regulator of basal lymphoid development. Early pre-clinical data also suggests that IL-7 may have a role in platelet production. PMID- 2189142 TI - Cytokine control of human megakaryocytopoiesis. PMID- 2189143 TI - Effects of the NMDA antagonists CPP and MK-801 on radial arm maze performance in rats. AB - The dose- and time-dependent effects of N-methyl-D-aspartate receptor/channel antagonists on radial 8-arm maze performance were examined in rats. Both CPP (1.0 30 mg/kg), a competitive NMDA antagonist, and MK-801 (0.1-1.0 mg/kg), a noncompetitive NMDA antagonist, produced dose-dependent increases in the number of errors made to sample all 8 baited arms. The effective doses of both drugs produced maximal performance impairments 2 hr after IP injection, and no effects after 24 hr. In a second radial arm maze task where only 4 arms were baited, CPP (10 mg/kg) had a somewhat greater effect on the number of working memory errors than on reference memory errors. MK-801 (0.1, 0.33 mg/kg) had no effects on either this task or on a task involving a 1-hr delay between correct choices 4 and 5 on the 8 choice task. CPP (10 mg/kg), however, impaired performance on this latter task. These results indicate that doses of NMDA antagonists, sufficient to block hippocampal long-term potentiation, also disrupt radial arm maze performance. PMID- 2189144 TI - Enantiomers of phenylpropanolamine suppress food intake in hyperphagic rats. AB - Phenylpropanolamine (PPA, d,l-norephedrine), available in many over-the-counter nasal decongestants and appetite suppressants, is a racemic mixture of the enantiomers d- and l-norephedrine. The present study evaluates the effects of the individual PPA enantiomers on a variety of nondrug (food deprivation) and drug induced hyperphagias (2-deoxyglucose and insulin). Racemic PPA has been shown to significantly suppress food intake in these hyperphagic models. Both l norephedrine (5-50 mg/kg) and d-norephedrine (5-150 mg/kg), administered intraperitoneally, significantly suppressed feeding after a 4-hr fast during the dark cycle. During the light period, l-norephedrine (7.5, 10, 15 mg/kg) and d norephedrine (75, 100, 150 mg/kg) significantly reduced food intake at the 1-hr and 3-hr time intervals in the 24-hr food deprivation-, insulin- and 2 deoxyglucose-induced hyperphagic models. Only 7.5 mg/kg l-norephedrine in the insulin-induced hyperphagia at 3 hr failed to significantly suppress feeding. These results indicate that each individual PPA enantiomer possesses the ability to suppress food intake in rats made hyperphagic by various stimuli. PMID- 2189145 TI - Inhibitory influence of excitatory amino acid antagonists on penicillin-induced epileptiform bursting in rat hippocampal slices. AB - The inhibitory influence of excitatory amino acid (E.A.A.) antagonists such as kynurenic acid, 2-amino-5-phosphonopentanoic acid (AP5), cis-2,3-piperidine dicarboxylic acid (cis-2,3 PDA) and (+)-5-methyl-10,11,-dihydro-5H dibenzo(a,d)cyclo-hepten-5,10-imine maleate (MK 801), has been studied on the epileptiform activity elicited in rat hippocampal slices, bathed in penicillin (1 mM). The rank of the inhibitory potency was: MK 801 greater than kynurenic acid greater than cis 2,3 PDA greater than AP5. Moreover, only MK 801 was able to block the last population spike of the penicillin-induced epileptiform bursting in 100% of the experiments. The data indicate that the antiepileptic activity of E.A.A. antagonists on the penicillin epileptiform bursting in CA1 pyramidal cells is low and limited, indicating that the hippocampal area is not the primary site of the anticonvulsant activity of E.A.A. antagonists. PMID- 2189146 TI - Treatment of benign paroxysmal positional vertigo. AB - Peripheral vestibular disorders result in vertigo, disequilibrium, and frequently nausea and vomiting. The purpose of this article is to describe the physical therapy management of one of the more common peripheral vestibular disorders- benign paroxysmal positional vertigo (BPPV). Several different approaches have been used in the treatment of BPPV. These approaches are compared, and the criteria used in choosing the appropriate approach are presented. Case studies are used to illustrate the different treatment approaches. PMID- 2189147 TI - Immunosuppressive treatment in membranous nephropathy [see comment]. PMID- 2189148 TI - Rational management of the 'on-off' syndrome in Parkinson's disease. PMID- 2189149 TI - The Medical Research Council trial of short-term high-dose alternate day prednisolone in idiopathic membranous nephropathy with nephrotic syndrome in adults. The MRC Glomerulonephritis Working Party. AB - We have assessed the medium-term effect of a short course of high-dose, alternate day prednisolone on adult nephrotic patients with membranous nephropathy, using a randomized, prospective, double-blind, controlled trial. Patients were entered over the period 1981 to 1984 and were observed for a minimum of three years. One hundred and seven adult patients who had not previously received immunosuppressive treatment were included in the trial. One hundred and sixty further patients, excluded from the trial, but with membranous nephropathy were identified, followed and assessed retrospectively at the end of the trial. At 36 months there was no significant difference between control and treatment groups in plasma creatinine, creatinine clearance or 24-h excretion of protein. At between three and six months serum albumin concentrations were higher and protein excretions lower in the treatment group compared to controls. No significant benefit was therefore observed on renal function in the medium term. PMID- 2189150 TI - Blood vessel physiology and pathophysiology. AB - The vascular system is complex, with functions in the active modulation of metabolic and hemodynamic processes as well as in transport. Vascular smooth muscle is the primary effector component of the vessel wall and is regulated in its activity by local endothelial cell and neural activity in addition to circulating substances. The vascular endothelial cell has only recently been fully recognized to possess a vast array of metabolic capabilities that are yet to be completely understood. Endothelial cell-derived vasoactive substances, their release, and interactions with blood constituents and vascular smooth muscle are new areas of clinical research which hold significant implications for the physiology and pathophysiology of blood vessels. PMID- 2189151 TI - Epidemiology of vasculitis. AB - Knowledge of the epidemiology of vasculitic syndromes in the general population is limited. With few exceptions, most of the syndromes are sufficiently infrequent that accurate population-based data are lacking. PMID- 2189152 TI - Roentgenographic findings in major vasculitic syndromes. AB - Angiography provides valuable diagnostic information in vasculitis. The diagnosis of vasculitis is made by identifying specific arterial abnormalities and their patterns of distribution. Based upon the specific disease in question, the scope of the angiographic procedure needs to be tailored to provide the answer. Other diagnostic modalities, such as Doppler ultrasound, computed tomography, and magnetic resonance imaging, have limited but important roles that have not been fully explored. PMID- 2189153 TI - Cutaneous vasculitis. AB - Cutaneous vasculitis comprises a wide spectrum of clinical syndromes and histopathologic findings which share the common theme of vascular inflammation and changes in the adjacent tissue. This article discusses several types of cutaneous vasculitides including leukocytoclastic vasculitis, Henoch-Schonlein purpura, urticarial vasculitis, livedoid vasculitis, and granulomatous vasculitides. The clinical patterns of these types of vasculitic syndromes as well as associated diseases and histopathology are discussed. PMID- 2189154 TI - Polymyalgia rheumatica. AB - Polymyalgia rheumatica is a syndrome that occurs in the elderly and is characterized by pain and stiffness involving the neck, the shoulder girdle, and the hip girdle. The aching should be present for greater than one month. Polymyalgia rheumatica may be more common than reported. The etiology remains unknown. There is generally little found pathologically in this disease. The physical examination is often not impressive. Synovitis may be a main contributing factor to many of the symptoms seen in patients with polymyalgia rheumatica. Symptoms often do not correlate with physical findings. Polymyalgia rheumatica must be differentiated from many conditions since the diagnosis remains entirely clinical. Osteoarthritis, flu syndromes, inflammatory myopathies, fibromyalgia, and depression all have features that may mimic polymyalgia rheumatica. Malignancies and infections may also be difficult to separate from polymyalgia rheumatica. Polymyalgia rheumatica may also be extremely difficult to differentiate from seronegative rheumatoid arthritis in patients older than 50 years. Although some patients with polymyalgia rheumatica have underlying giant cell arteritis, the majority apparently do not. The distinction between polymyalgia rheumatica and giant cell arteritis cannot be made on the basis of laboratory studies and relies solely on clinical symptoms and physical findings. Although nonsteroidal antiinflammatory medications may control symptoms in patients with mild disease, most patients with polymyalgia rheumatica require low-dose corticosteroids. The tapering schedule for the corticosteroids is contingent upon the response of symptoms and laboratory parameters. Polymyalgia rheumatica usually follows a benign course with almost complete response to an adequate treatment program. Recently, there have been several studies suggesting that the course of polymyalgia rheumatica may not be as short and simple as once proposed. Nevertheless, many patients may be completely weaned from corticosteroids. Other agents have been used in this disease, but for the most part their use remains somewhat controversial. Patients must be monitored carefully. Most patients do well, and treatment is effective. PMID- 2189155 TI - Kawasaki syndrome. AB - Kawasaki syndrome is an acute, self-limited illness of young children which is characterized by prolonged fever, mucositis, skin changes, and cervical lymphadenopathy. Most investigators favor a microbial agent or agents as the trigger of KS followed by an immune-mediated vasculitis with a predilection for the coronary arteries. Serious complications include coronary artery aneurysms, aneurysmal thrombosis, and death. Aspirin has been the conventional treatment for KS, but it has not been shown to alter the basic pathology. Recently intact intravenous gamma globulin has been shown to reduce the frequency of coronary artery abnormalities. Definitive therapy of KS, however, awaits the discovery of its cause and pathogenesis. PMID- 2189156 TI - Granulomatous vasculitis. Wegener's granulomatosis and Churg-Strauss syndrome. AB - Wegener's granulomatosis and the Churg-Strauss syndrome are both syndromes that appear to begin with a phase of regionally limited symptomatology before they progress at unpredictable rate to a generalized phase characterized by symptoms of systemic vasculitis. The clinical features of atopy, peripheral blood eosinophilia, and tissue eosinophilia distinguish CSS from WG, with its typical necrotizing granulomatous respiratory tract lesions. Whereas in generalized WG with renal involvement the use of cyclophosphamide usually cannot be avoided, the generalized systemic vasculitis phase of CSS appears to respond well to glucocorticoids alone. For the more limited forms of WG, adapted therapy regimens including trimethoprim-sulfamethoxazole have been reported to be successful. Anticytoplasmic autoantibodies (c-ANCA = ACPA) are a new diagnostic serum test with high specificity for WG. Serial determinations of c-ANCA are a promising tool to monitor disease activity. PMID- 2189157 TI - Giant cell (temporal) arteritis. AB - Giant cell arteritis is becoming recognized as one of the most common forms of vasculitis. However, its variable presentations and multiple features may make recognition difficult. Early diagnosis and treatment with cortico-steroids can prevent vascular occlusions. The challenge for the clinician is to use the lowest dose that suppresses the disease but also results in the fewest drug-related adverse effects. PMID- 2189158 TI - Vasculitis in Behcet's disease. AB - Vasculitis of arteries and veins is an important feature of Behcet's disease. When it occurs in systemic or pulmonary arteries or in large veins it is life threatening. Retinal vasculitis is the hallmark of eye disease, and much of the central nervous system disease is linked to small artery occlusions. Treatment with immunosuppressive drugs has improved the prognosis for sight and life. PMID- 2189159 TI - Vasculitis and Cogan's syndrome. AB - Cogan's syndrome is a rare syndrome manifested by nonsyphilitic interstitial keratitis and audiovestibular symptoms including hearing loss, tinnitus, and vertigo. Systemic manifestations may occur. Systemic vasculitis and aortic insufficiency secondary to aortitis and valvulitis are two of the most serious manifestations. PMID- 2189160 TI - Vasculitis and relapsing polychondritis. AB - Relapsing polychondritis is a systemic disease of unknown etiology with predominate manifestations of multiorgan cartilaginous inflammation. Although relapsing polychondritis occurs predominantly as a separately defined clinical complex, a significant number of patients may suffer from another rheumatic disease. Vasculitic syndromes are the most commonly observed disorders associated with relapsing polychondritis. PMID- 2189161 TI - Vasculitis associated with rheumatoid arthritis. AB - Vasculitis may accompany rheumatoid arthritis. One must distinguish between vascular involvement associated with the pathogenesis of rheumatoid arthritis, isolated digital vasculitis, and the syndrome of clinical rheumatoid vasculitis. The cause of clinical rheumatoid vasculitis is unknown. High titers of rheumatoid factor, cryoglobulins, diminished circulating complement, an increased prevalence of HLA-DR4, and the pathologic findings suggest an immune etiology. However, similar, but perhaps less pronounced, abnormalities occur in uncomplicated rheumatoid arthritis, and these findings are not universal in complicating vasculitis. Classic cutaneous clinical manifestations include ischemic ulcers, digital gangrene, and palpable purpura. Mononeuritis multiplex is another classic presentation of rheumatoid vasculitis. Small digital infarctions may accompany other manifestations in clinical vasculitis or may occur alone as isolated digital arteritis, in which case the prognosis is relatively favorable. Weight loss, pleuritis, pericarditis, ocular inflammation, splenomegaly, hepatomegaly, and Felty's syndrome have also been reported in association with rheumatoid vasculitis. Although renal involvement has been considered unusual in rheumatoid vasculitis, several studies suggest that this may be more common than previously recognized. Ideally, a biopsy or an angiogram confirms the diagnosis of rheumatoid vasculitis, but often the diagnosis rests upon the clinical picture. In general, blind biopsies are not helpful, although one series indicated that a blind rectal biopsy may be an exception to this rule. An elevated erythrocyte sedimentation rate, increased C-reactive protein level, anemia, thrombocytosis, hypoalbuminemia, and a positive rheumatoid factor are common laboratory findings. Leukocytosis, hypergammaglobinemia, leukocytopenia, an elevated creatinine level, and minimal abnormalities of the urinary sediment also occur in patients with rheumatoid vasculitis. However, these abnormalities overlap in patients with uncomplicated rheumatoid arthritis, and their role in distinguishing rheumatoid vasculitis from uncomplicated rheumatoid arthritis is limited. Other immunologic tests have no established clinical role in diagnosing rheumatoid vasculitis. Therapy depends upon the clinical manifestation of rheumatoid vasculitis. Uncomplicated rheumatoid arthritis deserves appropriate therapy, and general attention to nutrition, cessation of tobacco, and control of blood pressure are indicated for all patients. Isolated digital vasculitis generally requires no more than the usual treatment for uncomplicated rheumatoid arthritis. Appropriate dermatologic management is indicated for ischemic ulcers. Most clinical experience in managing more symptomatic rheumatoid vasculitis has focused on glucocorticosteroids, D-penicillamine, and cytotoxic immunosuppressive drugs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2189162 TI - Buerger's disease (thromboangiitis obliterans). AB - Thromboangiitis obliterans is a progressive, often relentless and devastating, vasculitis causing significant loss of digits and limbs in a youthful population of tobacco users. Whereas the specific pathogenetic mechanism has not been defined, tobacco use is clearly a trigger for what appears to be an autoimmune mechanism in a given group of patients. Its cessation almost always prevents further tissue damage. Medical and surgical therapy palliate accrued damage, but only complete abstinence from tobacco use allows stabilization of the process. An appreciation of the characteristic clinical, angiographic, and histopathologic features allows specific diagnosis and differentiation from premature atherosclerosis and other mechanisms of distal and microcirculatory deficits. There is a pressing need for the evaluation of agents that might interrupt this process in the face of continued tobacco use; such an agent would be helpful in combating proliferative arterial change in other types of vasculitis. PMID- 2189163 TI - Vasculopathy associated with the antiphospholipid antibody syndrome. AB - Antiphospholipid antibodies including the false-positive serologic test for syphilis, the lupus circulating anticoagulant, and the anticardiolipin antibody can be associated with recurrent thrombotic events, recurrent fetal loss, and thrombocytopenia. A range of other possible clinical associations also exists, including neurologic events, skin lesions, and cardiac lesions. The pathology of these lesions and the pathophysiology are discussed. Treatment is controversial but when indicated is directed toward prevention of recurrent episodes using anticoagulants including antiplatelet agents, warfarin, and heparin as well as occasionally prednisone with or without immunosuppressive agents. PMID- 2189164 TI - Ethylenethiourea (ETU) in relation to use of ethylenebisdithiocarbamate (EBDC) fungicides. AB - Degradation of ethylenebisdithiocarbamate fungicides (EBDCs) is known to produce ethylenethiourea (ETU). This article reviews the literature available on the toxicology of EBDCs and ETU, the sources in plants and persistence of ETU, and its formation during heat treatment of plant products. Detoxification techniques developed are mentioned, and Maximum Residue Limits and the results of monitoring studies are given for several countries. Some aspects of the methods of analysis are discussed. Although EBDCs have in the past been regarded as relatively harmless, data on their subchronic and chronic toxicity indicate that these toxicological features should not be ignored. ETU has low acute toxicity but possesses carcinogenic, goiterogenic, teratogenic, and mutagenic activity in animal tests. The most prominent aspect of its toxicology is its action on the thyroid gland, which causes hyperplasia and a decrease in thyroid hormone levels. It is a potent teratogen in pregnant rats after either acute exposure or administration throughout organogenesis, inducing a wide spectrum of malformations to the progeny. The teratogenic potential is specific to rat, whereas administration to pregnant mouse, hamster, guinea pig, and cat causes limited or no teratogenicity, except at very high dose levels. The mutagenicity of ETU has not been clearly established, although some data exist that indicate that it indeed has mutagenic potential. ETU can react with nitrites to form N nitroso-ETU, which is a mutagenic and teratogenic compound. Most of the ETU present in fresh agricultural products treated with EBDCs arises from the presence of ETU in formulations. Surface deposits of EBDCs on plants may be a secondary source. ETU may also be taken up by plants from the soil following the breakdown of EBDCs, but conflicting results have been obtained on this phenomenon. ETU on plant surfaces undergoes subsequent degradation. Although small amounts may persist up to 30 d after spraying, there is no indication that it accumulates in plants. Initial findings that ETU is formed during the heat processing of EBDC-treated foods are confirmed by the more recent literature. However, the variability of the results indicates a wide range of conversion due to processing. Boiling of spinach, pears, grapes, tomatoes, and wheat, treated with different EBDCs, resulted in 3-30% conversion to ETU. Apple juice, dried pomace, and applesauce contained more ETU than the EBDC-treated apples, from which these products were produced. This was also true for tomato juice and canned whole tomatoes. ETU may be produced in the smoke of tobacco containing high EBDC residues.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2189165 TI - Effects of oral and parenteral selenium supplements on residues in meat, milk and eggs. AB - Oral and parenteral preparations of Se are used worldwide to prevent and treat nutritional muscular dystrophy and other Se deficiency syndromes. There are extensive published data on the effects of oral supplementation on Se residues in food animal products. Very little published data exist on the effects of parenteral administration on Se residues, even for cattle and swine in which parenteral preparations are used extensively. The distribution of Se into kidney and liver appears to be equivalent for both forms of supplementation. Elimination of Se in milk is greater after parenteral administration and correlates with high plasma Se levels, however the milk excretion drops quickly and after 4 d returns to control levels (Little et al. 1979). Of particular interest is the finding that up to 18% of Se in an oral diet may be excreted in milk (Maus et al. 1980). Use of Se supplements in poultry results in increased levels of Se in liver, kidney, and eggs. Distribution of Se into liver and kidney is much greater than into breast muscle indicating a greater capacity of these organs to accumulate Se. Excretion of Se into eggs results in Se levels equivalent to those in liver and kidney, indicating that eggs are an important route of Se excretion in laying hens (Ort and Latshaw 1978). When Se supplementation stops, the liver, kidney, and egg white and yolk residues decline quickly to control values within 1-2 wk. Breast muscle Se content changes little during supplementation and after withdrawal of supplementation. Oral and parenteral selenium supplementation in swine result in greater accumulation of Se in liver and kidney than in muscle. Oral selenium supplementation also increases the excretion of Se into milk. This method has been used to prevent Se deficiency disease in piglets (Mahan et al. 1975). Oral supplementation with 0.1 ppm Se, as sodium selenate, did not result in levels of Se in blood, meat, or viscera at slaughter (Jenkins and Winter 1973). Despite the large amount of data available on Se residues in food animals, additional information on the pharmacokinetics of parenterally administered Se preparations is needed, especially in sheep and goats which receive parenteral Se supplements. Information on the disappearance kinetics of Se residues in meat and milk is needed for all ruminants. The data currently available in the literature does not allow the calculation of pharmacokinetic parameters of Se in any species. Properly performed pharmacokinetic studies would contribute a great deal towards a better understanding of how food animals utilize supplemental selenium.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2189166 TI - Lead exposure in early life: health consequences. AB - Until very recently it has been considered that of the many manifestations of lead toxicity, those involving the elaboration and function of hemoproteins occur at lower levels of lead exposure than any others. The critical target seems to be the enzyme heme synthetase, which is essential for the insertion of iron into the precursor, protoporphyrin IX. The major consequences of this effect, which have been evaluated in both adults and children, are reduction of circulating levels of hemoglobin and cytochrome P-450-dependent Phase I drug metabolism. Lead clearly inhibits normal hemoprotein function in both respects. The threshold level of lead exposure for these effects seems to be at a circulating lead concentration (PbB) of approximately 30 to 40 micrograms/dL. A growing body of evidence suggests, however, that the functional integrity of the central nervous system is compromised at substantially lower levels of lead exposure, particularly in the human fetus and young child. Early postnatal neurobehavioral development is compromised at maternal or cord PbB of somewhat less than approximately 10 micrograms/dL, a level of lead exposure not uncommon in the general population. Results of more recent cross-sectional and prospective studies indicate that postnatal lead exposure resulting in PbBs as low as 25 micrograms/dL, and probably lower, also are associated with deficits in intellectual attainment, achievement, and behavior. The long-term consequences of these effects remain to be fully evaluated. Little is known concerning basic mechanisms that are responsible for these effects. They may be manifestations of a more basic common effect of lead on cell proliferation and differentiation. PMID- 2189167 TI - An anti-Cryptococcus neoformans monoclonal antibody directed against galactoxylomannan. AB - Six monoclonal antibodies (mAb) were produced by immunizing mice with a Cryptococcus neoformans serotype A spheroplast lysate (CNSL). Two mAb were of the IgG1 isotype; the others were IgM. The results obtained with one IgM mAb (CN6) are reported herein. This mAb recognized the four serotypes of C. neoformans and no cross-reactions were observed with extracts from Cryptococcus melibiosum, Candida albicans, Saccharomyces cerevisiae, Torulopsis glabrata or Trichosporon beigelii. Fractionation of the CNSL by gel filtration revealed that mAb CN6 recognized high molecular weight substances as well as a range of smaller molecules. Indirect ELISA inhibition studies showed that this mAb recognized substances in a cryptococcal culture filtrate. Inhibition studies and agglutination tests using latex beads sensitized with purified CN6 showed that CN6 strongly reacted with the C. neoformans serotype A cell envelope galactoxylomannan-mannoprotein complex (GAlXM-MP) and only weakly with the glucuronoxylomannan (GXM) component. These tests also showed that purified galactoxylomannan (GalXM) from C. neoformans serotype A was more reactive than purified mannoprotein (MP). An anti-GalXM mAb might be a useful tool for monitoring the clinical course of cryptococcal infections. PMID- 2189168 TI - AIDS: non-infectious deficiencies acquired by drug consumption and other risk factors. PMID- 2189169 TI - rRNA gene restriction patterns of Leptospira: a molecular typing system. AB - A total of 67 serovar reference strains and 7 isolates belonging to the genus Leptospira were characterized by ribosomal ribonucleic acid (rRNA) gene restriction patterns. Fifty patterns were observed. Strains belonging to different genomic species always gave different patterns. However, genomic species were subdivided into several patterns. Forty-three serovars gave a specific pattern. Some serovars could not be separated by rRNA gene restriction patterns: strains of serovars icterohaemorrhagiae, copenhageni, lai, pyrogenes and jalna gave pattern 1; serovars birkini, mankarso and wolffi gave pattern 4; serovars canicola, gem, hebdomadis, pomona and hardjo (strain hardjoprajitno) gave pattern 12; serovars valbuzzi and zanoni gave pattern 14; serovars jonsis, malaya and sumneri gave pattern 16; serovars arborea, ballum, castellonis and kenya gave pattern 35; and serovars borincana and shermani gave pattern 43. These data provide the bases for a molecular typing system for the genus Leptospira. PMID- 2189170 TI - Killing of Mycobacterium avium: insights provided by the use of recombinant cytokines. PMID- 2189171 TI - HIV-specific cytotoxic T lymphocytes directed against alveolar macrophages in HIV infected patients. AB - A CD8+ lymphocytic infiltration of the lungs is frequently observed in HIV infected patients, even prior to the onset of opportunistic infections. In such patients, we could demonstrate that most of these CD8+ alveolar T lymphocytes displayed the D44 marker and were functional cytolytic T lymphocytes directed against autologous HIV-infected alveolar macrophages. This primary cytolytic activity was HLA-restricted and, at least partially, specific for the HIV envelope protein, since HLA-A2 alveolar T lymphocytes could specifically lyse cell lines expressing both the HLA-A2 and Env antigens. In contrast to data obtained in peripheral blood, no ADCC activity was observed against the Env antigen. HIV-specific alveolar T-lymphocyte cytolytic activity decreased with progression towards AIDS as shown by studies of a series of 40 patients. Functional abnormalities of the lung epithelium could be associated with the specific lysis of alveolar macrophages, suggesting that local tissue injury could result from the in vivo immune conflict between alveolar HIV-specific CTL and HIV infected macrophages. PMID- 2189172 TI - Functional abnormalities of monocytes/macrophages in HIV1-infected patients as demonstrated by the skin window procedure. AB - Skin window (SW) tests were performed in ten HIV1-infected patients and in ten healthy volunteers. The chemotaxis of monocytes/macrophages is weakened in AIDS patients, since the number of monocytes/macrophages attracted by the SW stimulus decreases in HIV1-infected subjects during the observation time, whereas the number increases in control individuals. HLA-DR expression decreases faster in AIDS patients than in healthy volunteers. Giant cell formation occurs and disappears earlier in HIV1-infected patients than in healthy control individuals. The results suggest that, at least in part, the impairment of chemotaxis and other functional abnormalities of mononuclear phagocytes are caused by their accelerated aging in HIV1-infected patients. PMID- 2189173 TI - Endocytosis mediated by monocyte and macrophage membrane lectins--application to antiviral drug targeting. AB - Sugar receptors, or membrane lectins, have been evidenced at the surface of various normal and tumour cells using fluoresceinylated neoglycoproteins (glycosylated bovine serum albumin (BSA]. By flow cytometry we have shown that macrophages bind and internalize mannosylated and 6-phosphomannosylated ligands in acidic compartments. Freshly isolated monocytes and U937, a promonocytic cell line, lack a mannose-specific receptor, but express mannose-6-phosphate (Man-6P) membrane lectin. Neoglycoproteins are potent drug carriers: muramyl dipeptide (MDP), an immunoactivator, when bound to Man-BSA or Man-6P-BSA, is 100 times more efficient than free MDP in activating macrophages; in vivo, it enables eradication of lung metastases in mice. Recently, neutral glycosylated biodegradable and nonimmunogenic polymers, were synthesized and found to be as efficient as neoglycoproteins. Antiviral drug conjugates were more active than the free drug, inhibiting the multiplication of virus (herpes) in human macrophages in vitro. PMID- 2189174 TI - The alveolar macrophage in sarcoidosis. AB - Sarcoidosis is characterized by the accumulation of lymphocytes and cells of the mononuclear phagocyte series (MPS) at sites of inflammation. MPS cells are central to the granulomatous response being capable of antigen presentation to T cells, production of the potent monokines, IL-1 and TNF-alpha, and the secretion of growth factors, all of which are of likely relevance to the disease process. Bronchoalveolar lavage, monoclonal antibodies and molecular biology techniques have been invaluable tools in our understanding of the inflammation. These approaches will continue to be critical to resolving important questions relating to disease pathogenesis and treatment. PMID- 2189175 TI - The pathology of granulomatous diseases of the thyroid gland. AB - In the present review we comment on granulomatous diseases of the thyroid gland based mainly on combined clinico-pathological criteria. Emphasis is given to diseases restricted to the thyroid (i.e., de Quervain's, palpation and interstitial giant cell thyroiditis), and those that may manifest as primary in the thyroid though they may be part of a generalized process (i.e., sarcoidal, tuberculous, fungal and syphilitic thyroiditis). Other disorders with minor variable granulomatous or pseudogranulomatous components affecting the thyroid are briefly described, and differential diagnoses analysed for granulomatous lesions both specific and non-specific to the thyroid. PMID- 2189176 TI - That strangeness in your smile. PMID- 2189177 TI - Botulism. PMID- 2189178 TI - Tick bite paralysis. PMID- 2189179 TI - Lambert-Eaton syndrome. AB - LES is an autoimmune disorder of the neuromuscular junction in which autoantibodies directed against voltage-dependent Ca2+ channels block nerve evoked Ca2+ entry at the motor nerve terminal. The pathogenic IgG is likely to produce a similar inhibitory effect on the Ca2+ channel function in other cholinergic synapses of the autonomic nervous system. This pathophysiology is sufficient to account for the distinctive clinical, immunologic, and electrophysiologic manifestations in patients with LES. Etiology of this disease is uncertain but in view of its frequent association with small cell lung cancer, this specific type of neoplasm may be implicated in the initiation of autoimmune response. Recent studies indeed support the possibility that the antigenic stimulus in the neoplastic form of LES may arise from voltage-dependent Ca2+ channels found in the lung cancer cells. PMID- 2189180 TI - Organophosphate intoxication: pharmacologic, neurophysiologic, clinical, and therapeutic considerations. PMID- 2189181 TI - Neurotoxic snake envenoming. PMID- 2189182 TI - Diagnosis of myasthenia gravis in the 1990s. AB - We have tried to show through this analysis how an understanding of the characteristics of diagnostic tests can lead one to a rational strategy for making clinical decisions. The diagnosis of MG can be made with a high degree of confidence in most situations, but the amount of supporting test information necessary depends on the clinical situation. This analysis does show some general guiding principles. The first is that the results of the edrophonium test should be used to guide further diagnostic assessment in most situations. In the small number of cases in which an objective edrophonium test cannot be done, the pretesting estimate of certainty should be used to guide testing strategy. A second principle is that, if a second diagnostic test is required after edrophonium testing, it should be the acetylcholine receptor antibody assay. This test is less expensive and it has more overall reliability. EMG testing thus serves as a third-line test for MG, and it can be reserved for a small number of clinical situations in which certainty about the diagnostic test is too high to reject the possibility of MG, yet too low to initiate treatment confidently. The greatest attractiveness of this type of analysis is that one may take issue with one or more of the assumptions on which it is based without invalidating the conclusions. The conclusions can be tested by a process called sensitivity analysis, in which one or more of the variables can be changed to study its effect on the outcome of the analysis. For example, one could require that certainty exceed 99% (T1) prior to beginning treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189183 TI - Rational therapy of myasthenia gravis. PMID- 2189184 TI - Thymoma: diagnosis and management. PMID- 2189185 TI - How much data should we collect in a randomized clinical trial? AB - Multicentre randomized controlled clinical trials are usually designed to answer a specific question. In accomplishing this they often collect a large quantity of data during screening, baseline and follow-up visits. These data are not all necessarily related to the main study question. This collection impacts on the overall recruitment process and the participants' time. During the planning phase of the trial we need to consider the reasons for collecting data and the use of that data for the current study as well as its potential use in future investigations. We discuss briefly some of the possible reasons that data may be collected: screening or determining eligibility; conducting a run-in or dose titration phase; assessing group comparability; aiding patient management; evaluating the natural history of the disease; monitoring the study; testing the study hypotheses; evaluating adherence; estimating side effects and the use of other therapies; analysis of other study questions. PMID- 2189186 TI - An evaluation of central laboratories in three VA cooperative studies. AB - We compared central laboratory with local determinations of key clinical measurements in three VA Cooperative Studies. Electrocardiographic evidence of new myocardial infarction was assessed in the study of Aspirin Therapy and Unstable Angina, ejection fraction measurement in the Coronary Artery Bypass Surgery Trial and lesion size in the Angioplasty Compared with Medicine (ACME) Trial. The findings in the Aspirin Trial indicated that central coding of all serial electrocardiograms in 1266 patients to detect new acute myocardial infarction by computer algorithm was not cost-effective when compared with the local investigator's diagnosis on the basis of a central Electrocardiographic Committee as the reference standard. In the other two trials, the contribution of the central laboratories was important because the assessments of the local investigators generally underestimated the degree of abnormality in the Bypass Trial and overestimated it in the ACME Trial. The VA results have clearly demonstrated two cases in which the decision for central evaluation was prudent, but one case in which it was not cost-effective. These equivocal findings indicate the need to evaluate the contribution of central laboratories when used as an adjunct to local determinations. Such evaluations may provide guidelines for decision-making in the design of future trials. PMID- 2189188 TI - A clinic's perspective on screening, recruitment and data collection. AB - This paper summarizes the approach of one university cardiology section with over a decade of experience in conducting National Institutes of Health and pharmaceutical cardiovascular trials. Many of the organizational and personnel issues discussed can be directly applied to most university cardiovascular clinical research settings. Other aspects reflect a very specialized approach but key features can be modified or adapted to smaller individual research clinics. In terms of organizational features, our multi-hospital recruitment effort is co ordinated by a weekly clinical research conference which is attended by all nurse coordinators and cardiology fellows. Centralization of all clinic facilities and non-invasive laboratories, the central computer facility, and the availability of clinical research inpatient hospital beds facilitate our clinical research effort. An expanded role of the nurse co-ordinator is considered pivotal to trial performance. Suggestions are made as to the identification and recruitment of ideal nurse co-ordinators, maximizing their productivity, and retaining them. The key feature is the physicians' acceptance of the nurse co-ordinator as a colleague. The roles of the principal investigator and clinical cardiology fellows are delineated, and suggestions made for data entry and computer technical expertise to optimize nurse co-ordinator efficiency, allowing total focus on recruitment and follow-up. PMID- 2189187 TI - Polio trial: an early efficient clinical trial. AB - The Salk Vaccine Field Trial was a randomized, placebo-controlled trial designed to test the efficacy of the Salk killed virus vaccine. Although the trial was not without some problems, both in design and analysis, none was important enough to raise serious questions about the results. Thus, the design of the Field Trial was well adapted to the demanding requirements. The trial owes its success in a large part to substantial public involvement. In designing future, large-scale, simple trials, we may still be able to benefit from the lessons of the Polio Vaccine Trial. PMID- 2189190 TI - Clinical implications of pathologic subtypes in renal cell carcinoma. PMID- 2189189 TI - Efficient means of studying ancillary questions in clinical trials. AB - Ancillary questions in clinical trials can often be answered by studying subcohorts of the participants. If the question compares responses between treatment groups, a subcohort that preserves the randomization can be used. However, if the question can be answered by analysis within a treatment group or by combining treatment groups, efficient methods developed for observational studies can be used. These methods include case-control and case-cohort methods. PMID- 2189191 TI - The testicular biopsy in the evaluation of infertility. PMID- 2189192 TI - New developments in grading prostate cancer. PMID- 2189193 TI - Origin of oncologic anesthetic techniques. AB - The patient with cancer poses a challenge to the anesthesiologist for a variety of reasons including the effects of cancer (altered hemostasis, depressed immune response, and compromised airways), the effects of chemotherapy (malfunction of the myocardium, lungs, kidneys, and bone marrow; depression of pseudocholinesterase; and production of the syndrome of inappropriate secretion of antidiuretic hormone), as well as effects of radical cancer surgery (massive blood loss and the need for prolonged anesthesia). Anesthetic techniques to address these problems had their beginnings in the Department of Anesthesiology at Memorial Sloan-Kettering Cancer Center. This paper traces the development of modern oncologic anesthesia and discusses how these advances significantly reduced operative mortality. PMID- 2189194 TI - Nitrous oxide: a cause of cancer or chemotherapeutic adjuvant? AB - The administration of nitrous oxide rapidly inactivates the vitamin B12-dependent enzyme methionine synthase. This inactivation disrupts the normal interrelationships between vitamin B12 and folic acid, and results in altered levels of folic acid derivatives and certain amino acids and their metabolites. Attempts have been made to use the antifolate properties of nitrous oxide to treat patients with leukemia. Although transient improvements may be observed in patients with leukemia who are given nitrous oxide, prolonged administration of nitrous oxide is highly toxic and causes marked hematological and neurological abnormalities. Animal and in vitro studies suggest that the action of nitrous oxide may be tumor selective, and that nitrous oxide may interact with and enhance the therapeutic effect of other antitumor agents. However, there is a delicate balance between the possible beneficial and harmful effects of nitrous oxide, and the conditions for which nitrous oxide may prove useful as a chemotherapeutic adjuvant remain to be defined. Concern has also been raised that nitrous oxide may have carcinogenic potential, especially in operating room and dental personnel who are chronically exposed to trace concentrations of this gas. However, there is no convincing evidence to date that nitrous oxide causes cancer in either animals or humans. PMID- 2189195 TI - Anesthetic considerations in the pediatric cancer patient. AB - Cancer is second only to trauma as the leading cause of death in children 1-15 years of age. Pediatric cancer patients have unique physiologic, pharmacologic, and psychologic considerations that present a unique challenge to plan anesthesiologist. A thorough understanding of pediatric tumors, along with chemotherapeutics and their complications, is necessary to plan anesthetic management properly. Special attention is directed to the psychologic needs and preparation of both the patient and parents. Close cooperation and coordination among the pediatric oncologist, surgeon, and anesthesiologist are necessary for safe and expeditious operative care. PMID- 2189196 TI - Pain management of the oncologic patient. AB - After the first 5 years of life, cancer is one of the three most common causes of death. Most investigations of cancer pain have shown that 50-70% of patients suffer needlessly. Pain may be due to the tumor or a co-existant benign pain syndrome. Methods of pain management include: 1) neurolytic blockade: stellate ganglion block, celiac plexus block, lumbar sympathetic block, epidural phenol, subarachnoid neurolysis; and 2) non-pharmacologic methods: radiofrequency thermocoagulation lumbar sympathectomy, transcutaneous nerve stimulation (TENS), dorsal column stimulation (DCS). In summary, we utilize every possible combination of therapeutic modalities for cancer pain management. With so many safe procedures available, we encourage the primary physician to refer patients early in their disease process. Neurolytic procedures should be performed prior to initiation of high dose narcotic therapy, radiation, chemotherapy, and surgery when possible. PMID- 2189197 TI - Intraspinal narcotics for treatment of cancer pain. AB - Inadequate pain relief remains a problem for many patients with cancer. Narcotic administration by the epidural or subarachnoid route is a relatively recent innovation and is indicated when pain is poorly controlled with high doses of systemic narcotics, or when patients experience limiting narcotic side effects. When given by the epidural or intrathecal route, narcotics have a longer duration of action and a lower dose is effective. These techniques involve personnel trained in catheter insertion and maintenance. Epidural and intrathecal administration of narcotics is an alternative when oral narcotics are ineffective. In this report the term "intraspinal" refers to epidural and/or subarachnoid placement of catheters and drugs. PMID- 2189198 TI - Ambulatory anesthesia. AB - Ambulatory surgical procedures are a large and increasing fraction of all surgery in the United States. A specialized health care team must be assembled to care for these patients and meet their special needs. Ambulatory surgery patients should be selected according to medical and psychosocial criteria. Patient preparation includes a history and physical examination, limited laboratory tests, empty stomach, and appropriate monitoring. Premedication should be supportive, and verbal as well as medicinal; drugs include ataractics and analgesics. All forms of general or regional anesthesia may be used. Recovery goals must be well defined, aiming for "home readiness." Ambulatory anesthesia care is concluded with postdischarge follow-up, for quality assurance and risk management. PMID- 2189199 TI - Anesthetic technique for safe laser use in surgery. AB - The use of lasers has simplified, shortened, and made less traumatic many surgical procedures. It has also increased the range of conditions amenable to treatment in all of the surgical specialties. There are, however, potentially serious hazards associated with the surgical use of lasers. The most serious hazards are explosions and fire, particularly during surgery on the airway, where flammable material, i.e., the endotracheal tube, high oxygen concentrations, and the laser, which is a high energy ignition source, are in close proximity. This report deals with techniques of anesthesia delivery that minimize the risks to the patient and operating room environment consequent on laser use in the airway. Laser use elsewhere in or on the body is associated with no greater danger than the use of electrocautery and requires no special anesthetic adaptation. PMID- 2189200 TI - Anesthetic considerations for gynecologic cancer surgery. AB - Preoperative, intraoperative, and postoperative anesthetic considerations in gynecologic cancer surgery are discussed. Preoperatively, the anesthetist must document the patient's disease state, physical condition, responses to prior chemotherapeutic regimens and toxic side effects, particularly from Adriamycin and bleomycin. Laboratory studies should include electrolytes, hepatic, renal, and hematologic indices. The anesthetist should also recognize that patients may be under great emotional stress, which may require prescribing anti-anxiety medications for several days prior to surgery. Planning the anesthetic includes consultation with the surgeon relative to procedure planned, positioning requirements, anticipated blood loss, monitoring and postoperative care requirements. Intraoperative considerations again involve close communication with the surgeon. The use and benefits of a combined regional/general anesthetic technique are discussed. Postoperative considerations are directed toward hemodynamic stability and control of postoperative pain. Techniques of epidural narcotic and local anesthetic administration, as well as patient-controlled analgesia (PCA) are discussed. PMID- 2189201 TI - [The importance of i.v. DSA in the diagnosis of acute pulmonary embolism]. AB - The high mortality rate of pulmonary embolism requires rapid and rational diagnosis especially with regard to the necessary decision about the best possible treatment. Analysis of data published in the literature, and of our own data, show that angiography of the a. pulmonalis according to the i.v. DSA technique is of central importance. This involves fewer hazards than conventional pulmonalis angiography while being comparatively satisfactory in respect of reliability of the results (more than 90%). It is, therefore, a safe basis for deciding on the appropriate treatment: lysis or surgery. PMID- 2189202 TI - [Color-coded Doppler sonography of deep venous thrombosis--possibilities and limitations in the area of the veins of the pelvis and the lower leg including postthrombotic changes]. AB - A comparative angiodynographic and phlebographic examination of 150 extremities in a total of 119 patients was performed in respect of the visualisation of the veins of the pelvis and lower leg. Controls regarding the course of disease with conservative treatment of a thrombotic occlusion were carried out between the 2nd and 6th weeks after the acute incident. Despite restricted examination conditions in the pelvic region, the examination yields satisfactory proof of the presence or non-existence of an iliac vein thrombosis. Improved flow detection enables the visualisation of the veins of the lower leg and the diagnosis even of incomplete thromboses of the veins of the lower leg. Colour-coded Doppler sonography is highly sensitive in detecting postthrombotic vascular changes, and hence angiodynography is a non-invasive method that is useful in checking on the success of conservative therapy subsequent to the treatment. This method is an essential improvement compared with conventional sonography in respect of the difficult differentiation between fresh venous thromboses and late postthrombotic changes. PMID- 2189203 TI - [Multiple aneurysms of unknown etiology in childhood--complications and diagnostic possibilities]. AB - A 6.5-year old boy with already known multiple aneurysms of all major arteries presented with acute abdominal pain. As demonstrated by ultrasound a big aneurysm of the left renal artery thrombosed in the course of three days. As a result, the left kidney developed severe ischaemia. Although computed tomography and scintigraphy were applied, a plan for a definitive therapeutic procedure could be established only by arterial angiography. Both Ehlers-Danlos' syndrome and Kawasaki's syndrome were excluded. There were no facts suggesting an infective aetiology. Four other cases with multiple aneurysms of unknown aetiology in childhood have so far been described in literature. PMID- 2189204 TI - [Radiologic diagnosis of hemorrhages of the gastrointestinal tract]. AB - In the diagnosis of acute gastrointestinal bleeding, endoscopy holds the first place today. Radiological investigations are indispensable whenever endoscopy cannot precisely localise the bleeding site, whenever a tumour is present or suspected, in all cases of lower gastrointestinal bleeding, and in haemobilia. A tailored radiological approach is recommended. The radiological basis programme should be at least a complete abdominal ultrasound study and plain abdominal radiograms. CT and ERCP scans may become necessary in selected cases. As a rule, angiographical localisation of the bleeding site will be successful only in the acute stage; selective visceral arteriograms have to be obtained, which may be executed in the digital subtraction technique in patients who are cooperating and clinically stable. Angiodysplasias and aneurysms, however, may be demonstrated angiographically in the interval as well. Upper and/or lower G.I. tract studies with barium or water-soluble contrast media may be indicated in the interval in order to demonstrate tumours, metastatic lesions, diverticula and gut malformations. PMID- 2189205 TI - [Medical treatment of endometriosis]. AB - The causal treatment of endometriosis is based on the fact that the disease is hormone-dependent. As it has been well established that endometriotic lesions heal at the end of pregnancy or after menopause, the principle of medical treatment is to imitate the effects of one or the other of these two situations by means of oestrogen-progestogen combinations, high-dose progestogen therapy or, more recently, analogues of LH-RH agonists. These treatments have proved to be effective on the lesions but they do not prevent recurrences. The indications of medical treatments administered alone or combined with surgery are still much debated. PMID- 2189206 TI - General metrological requirements of clinical lipid measurements. AB - Quantities in blood, plasma, or serum having lipid components are often difficult to define, especially as regards the component which must be selected according to chemical, biological, and clinical considerations. The choice of generic quantities and their respective measurement procedures relates to clinical requirements of allowable uncertainty, effectiveness, comparability, and compatibility determining goals of analytical reliability. The measurement procedure should define preanalytical requirements and be based upon traceability from tertiary and secondary reference materials with reference procedure values to primary reference materials. Such materials and procedures should be established internationally. A comprehensive quality assurance system of internal quality control and external quality assessment is essential to ensure worldwide and continued comparability. Validation and transferability should also be demonstrated by regional or international collaboration. Transmutation of results between procedures requires extensive investigations. PMID- 2189207 TI - Reference system for cholesterol measurements. AB - A reference system for cholesterol measurement is necessary to assure accuracy of cholesterol measurements by clinical, research, and manufacturers' laboratories. Such a reference system is based on the collaboration of laboratory and clinical professionals, research groups, professional societies, government groups, and manufacturers of diagnostic products. Essential components include a definitive method, a reference method, and commutable reference materials that are accurately labeled and have long-term stability. A mechanism by which clinical, research, and manufacturers' laboratories can establish traceability to the reference system is also needed. In the United States, the NRS/CHOL was organized as part of the National Reference System for the Clinical Laboratory. The major organizational components of the NRS/CHOL include the National Institute for Standards and Technology, the CDC, the CRMN, the CAP, the AAB, regional reference programs, and manufacturers of cholesterol diagnostic products. The NIST maintains an isotope dilution-mass spectrometer definitive method and distributes certified reference materials. The CDC maintains a modified Abell-Levy-Brodie Kendall reference method and offers a CDC-NHLBI Lipid Standardization Program; the CRMN provides reference method analyses on specimens furnished by manufacturers and clinical or research laboratories; CAP, AAB, and regional reference programs provide either proficiency testing, quality assurance programs, or both; and manufacturers assure that results on diagnostic products are the same as those achieved when using fresh patient specimens and the NRS/CHOL reference method. The NRS/CHOL has contributed much to the success of clinical epidemiologic and research and development investigations in coronary heart disease. PMID- 2189208 TI - Lipid risk factors and atherosclerosis: what do we measure? AB - Coronary atherosclerotic disease remains the major cause of mortality and morbidity in western societies. Despite significant reductions in the incidence of death associated with the disorder over the last 30 years, especially in the United States, there is an urgent need to identify more clearly the underlying causative agents so that primary and secondary prevention programs can be implemented. A number of lipid parameters such as total and LDL-cholesterol have withstood long-term evaluation, and have met all the criteria necessary to designate them as playing a causative role in coronary atherosclerosis. These two parameters, especially LDL-cholesterol, is now the focus of a number of public health initiatives in various countries. The role of HDL-cholesterol is still not yet certain, while that of triglycerides is still clouded. A host of newer lipid associated (apolipoprotein) parameters are currently under investigation and it will be a number of years before any of these could be designated in the same class as LDL-cholesterol. Among the apolipoprotein measurements, Apo B appears to be the most promising in terms of meeting requirements to elevate it from risk factor to causative agent. PMID- 2189209 TI - Improving the quality of plasma cholesterol measurements in primary care. AB - During the last 2 years an external quality assessment (EQA) scheme has been developed for plasma cholesterol measurements made in primary care. The scheme, which is supported by the UK Department of Health and by the instrument manufacturers, now has over 300 participants, most of whom use the Boehringer Reflotron. Operators are mostly nurses, with little or no laboratory experience. To avoid matrix effects, fresh plasma specimens collected from normal volunteers and those attending a hospital lipid clinic are used. Three specimens, mostly with cholesterol concentrations in the range 5-9 mmol/L, are distributed every 2 months. The mean plasma cholesterol results show good agreement with those from 'reference' laboratories, and efforts are now being made to link these laboratories with the CDC-based reference system. The scheme uses a predominantly graphical presentation of results, with a greater element of interpretation by the organisers than is usually provided for laboratory-based participants. The distribution of results shows a higher proportion of outliers than in the UK national EQA scheme for laboratory cholesterol measurements. At present about 10% of participants in primary care obtain results which could be clinically misleading, and new approaches are needed in dealing with these 'poor performers'. This scheme could serve as a model for other assays in primary care. It illustrates the importance of training, quality assurance and education, and the need for laboratory staff to become more involved in this growing and important area of laboratory medicine. PMID- 2189210 TI - Influence of analytical quality and preanalytical variations on measurements of cholesterol in screening programmes. AB - In screening programmes one should distinguish between the traditional bimodal distributions of results and a unimodal distribution as the basis for interpretation. A model for evaluation of the effects of biological within subject and preanalytical variation as well as analytical variation is described. It is concluded that bias from blood sampling and analytical performance influences the outcome of screening programs significantly. At least three blood specimens are needed for estimating the homeostatic set point of cholesterol in individuals. PMID- 2189211 TI - Action limits in hyperlipidemia. AB - One international and numerous national bodies have adopted action limits and guidelines for diagnosis and treatment of hyperlipidemia. The most publicized are those adopted by the European Atherosclerosis Society and by the National Cholesterol Education Program in the USA. Although differing in details, these guidelines share fairly low action limits based on observational epidemiology demonstrating increasing risk of cardiovascular disease in persons with serum cholesterol concentrations over 4-5 mmol/L. Various national bodies within Europe have adopted similar guidelines. In other countries, higher and therefore more conservative action limits have been proposed. They are primarily based on results of intervention studies. Seemingly small, differences between action limits may encompass a large part of the population. PMID- 2189212 TI - Biological variation in serum lipid concentrations. AB - Individual variations in serum lipid concentrations resulting from laboratory error are often much less than those due to other factors. Thus the coefficient of variation for biological fluctuations in cholesterol is 5-10% and for triglyceride concentration 5-25%. Many of the causes of changing lipid levels are known. Sampling conditions (venous stasis, body position) contribute as does the handling of the blood sample before it reaches the laboratory, for example whether an anticoagulant is used and haemolysis, clearly meals have a major effect on serum triglycerides, but even when fasting there is probably also diurnal variation. Fluctuations in serum lipids occur during the menstrual cycle, cholesterol and triglycerides tending to be highest at midcycle and to decline towards menstruation. Pregnancy produces major increases in both cholesterol and triglyceride levels. There is a well established seasonal variation in cholesterol concentrations which are greatest in autumn and lowest in late spring and early summer. This may be partly due to nutritional changes, but similar findings in laboratory animals suggest that humoral factors may also be important. Age also influences serum lipids. It is frequently not appreciated that both cholesterol and triglycerides are at their lowest in adolescence. Rapid increases in cholesterol may occur in women around the menopause. Lipid concentrations may undergo considerable change during illness. The decrease in LDL and HDL cholesterol and apo B and tendency for increases in triglycerides during acute myocardial infarction are well known but similar alterations can also occur with angina or coronary artery bypass surgery. Other surgical operations and intercurrent illnesses, perhaps even common viral infections, may also influence lipids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189213 TI - Laboratory measurement of lipid and lipoprotein risk factors. AB - Accuracy in measurement of serum cholesterol and the other lipid risk factors is essential for reliable patient classification within the context of newly implemented national coronary heart disease intervention programs utilizing uniform cutpoints. This requires agreement or traceability of laboratory methods to national reference systems, which provided the accuracy base for the population studies from which the cutpoints are derived. Adhering to accepted guidelines for patient preparation, blood collection and processing will minimize preanalytical variability. Standardization of the lipid/lipoprotein assays is the next essential step. The assay technology for cholesterol measurement is reasonably mature, although still not perfected; recent activities have focused primarily on achieving traceability of field methods through improving access to the accuracy base, the National Reference System for Cholesterol and developing better (commutable) reference materials. A major hindrance to standardization has been matrix interactions; alterations in reference materials from their preparation which change the measurement characteristics, necessitating the use of fresh specimens in accuracy studies. Considering the importance of LDL cholesterol which is the primary decision parameter in the new clinical guidelines; methodology for routine laboratory quantification is substantially lacking, the usual routine approach still involving estimation. Efforts to develop a reference system for LDL are just beginning. Field methods for HDL cholesterol are reasonably reliable but with some inter-method differences. Agreement on and access to a Reference Method is needed. Accuracy in triglyceride measurement is less important compared to the other risk factors. Convenient methods allowing correction for the free glycerol blank and ready access to a Reference Method are needed. PMID- 2189214 TI - Immunological typing of acute leukaemias by rosetting with immunomagnetic beads: comparison with immunofluorescence staining. AB - Immunological phenotyping of acute leukaemias is important for a more precise diagnosis with respect to both cell lineage and maturation level. We have developed a rapid and reliable method for immunophenotyping, based on the use of magnetic monodisperse beads coated with monoclonal antibodies. After only a 10 min incubation of immunomagnetic beads (IMB) with mononuclear cells isolated from bone marrow or peripheral blood, the percentage of rosetting cells can be counted in the microscope. A panel of 16 monoclonal antibodies against haematopoietic cell-surface antigens was applied on 29 cases of acute myelogenic (AML) or lymphocytic (ALL) leukaemias, in order to compare immunological typing by immunomagnetic beads with immunofluorescence staining (IF). In all the cases tested, the two methods showed a virtually identical antigen distribution. The procedure described offers the advantages of being fast and simple to perform. Moreover, it has a high specificity and is easy to interpret in cases with low antigen expression. PMID- 2189215 TI - Quantification of non-activated (native) complement component C9 synthesized by alveolar macrophages from patients with sarcoidosis. AB - Alveolar macrophages (AM) from sarcoidosis patients synthesize the functional alternative and terminal pathways of complement, and increased complement production may be one of multiple factors in the pathogenesis of sarcoidosis. We thus examined whether AM from sarcoidosis patients produced quantitatively more C9 in vitro than AM from healthy controls. AM from 16 patients with active sarcoidosis and seven healthy controls were cultured under serum-free conditions for 6, 12, 24, 48, or 72 h. A quantitative production of C9 was found in the harvested medium in 10 of 16 sarcoidosis patients. There were no detectable levels of C9 in the seven controls. Activated C9 was found in all patients and in the majority of the controls. C9 was quantified by an enzyme immunoassay based on a monoclonal antibody (M1) to non-activated C9. Our results indicate greater production of C9 by sarcoidosis AM than by their healthy counterparts. PMID- 2189216 TI - Human behavioral toxicology. Central nervous effects of low-dose exposure to neurotoxic substances in the work environment. AB - The central nervous effects of low-dose exposure to the neurotoxic substances found in the work environment can manifest themselves both as adverse subjective reactions and as performance impairments and physiological changes. The acute manifestations of these effects can be studied under highly controlled conditions in laboratory experiments on volunteers or in quasi-experimental field studies on occupationally exposed workers. The effects of long-term occupational exposure are commonly studied with the use of epidemiologic techniques in cross-sectional investigations or cohort studies. In addition studies using data from clinical cases have been conducted to describe the chronic effects of exposure. Although these types of investigations can provide valuable information on the health hazards due to the neurotoxicity of different substances, their accomplishment encounters theoretical and practical problems, some of which are described and discussed in the present paper. PMID- 2189217 TI - Subjective, behavioral and psychophysiological effects of noise. AB - The subjective and psychophysiological responses to noise and the effects of noise on performance have been reviewed in this article. Emphasis was placed on moderate-intensity noise and on the effects relevant for occupational noise exposure. It was concluded that in many respects research presents a rather inconsistent picture of these effects. Still, it is evident that the nonauditory effects of noise may be serious enough to warrant as much general attention in the occupational setting as has for some time been accorded in residential settings. PMID- 2189218 TI - Psychological aspects of occupational vibration. AB - A short review is given of the subjective responses to vibration (primarily whole body vibration) and of its performance and psychophysiological effects. The subjective importance of the basic physical vibration parameters and the effects of whole-body vibration on performance of tasks requiring manual control and visual acuity have been well covered by research, whereas knowledge of the effects on cognitive performance is rather meager. PMID- 2189219 TI - Thermal stress and human performance. AB - There is evidence that the thermal stress encountered in many work environments may negatively affect various aspects of human performance and behavior. Evaluation of the empirical research is, however, complicated by differences in both the methodology and the definition of the basic stimulus. Effects of heat and cold stress are briefly reviewed, with particular regard to theoretical considerations. PMID- 2189220 TI - Behavioral and psychophysiological effects of the physical work environment. Research strategies and measurement methods. AB - An international course on the behavioral and psychophysiological effects of the physical work environment was held in Stockholm, Sweden, in April 1988 by the Nordic Institute of Advanced Training in Occupational Health and the Swedish National Institute of Occupational Health. It dealt primarily with the behavioral and psychophysiological responses to aspects of the physical work environment and was devoted to neural and behavioral functions. The increasing interest in these functions is mainly motivated by the involvement of the central nervous system in the adverse effects induced by unfavorable environmental conditions of the workplace and by the need for more sensitive indicators than those based solely on recognized occupational disease and pathology. By describing the main aspects of the research strategies and the measurement methods used in this field of research, this paper provides a background for the assessment and evaluation of the early behavioral and psychophysiological indices of potential occupational hazards. PMID- 2189221 TI - Physiological and psychological effects of exposure to extremely low-frequency electric and magnetic fields on humans. AB - Research into the hypothetical adverse effects on health that might result from living or working in the proximity of high-voltage power lines has been intense over the last decade. The present paper provides a brief review of the human studies concerned with the physiological and psychological effects of exposure to extremely low-frequency electric and magnetic fields. It was concluded that, on the basis of available experience, electric and magnetic fields associated with transmission lines do not cause physiological or psychological effects to be considered as health hazards. PMID- 2189222 TI - Perception of effort in manual materials handling. AB - Measurement of subjective work load has emerged as a central topic of interest in the study of physical work and effort. From the practical point of view, subjective estimates of physical effort can contribute greatly to the assessment of work loads in physical activities and to the design of manual handling tasks. The rationale of this approach is that subjective estimates reflect the individual perception of the amount of physical and motivational resources that the subjects invest to meet the demand imposed by the physical task. The present paper provides an illustration of some of the techniques used in measuring the perception of physical effort and reviews and discusses the main results obtained with these techniques in the assessment of manual materials handling. PMID- 2189223 TI - Psychological and psychophysiological effects of shift work. AB - The psychophysiology of shift work is mainly related to circadian rhythmicity and sleep-wake phenomena. Individuals on a rotating three-shift or similar system work the night shift at the low phase of circadian rhythm. On retiring to bed in the morning they fall asleep rapidly but are prematurely awakened by their circadian rhythm and exhibit severe sleepiness and reduced performance capacity. In connection with the morning shift the circadian psychophysiology makes it difficult to fall asleep as early as needed during the preceding night. Around 0400 to 0500, when the individuals should rise, they have difficulties awakening because of the sleep loss and the circadian rhythm, which at that point is at its lowest. Subsequently, day work is characterized by sleepiness and reduced performance. It should be emphasized that it does not seem possible to improve one's ability to adjust over time, even with permanent night work. Older age and "morningness" personality are related to higher than average problems in adjusting. PMID- 2189224 TI - [Hand surgery. Soft tissue defects]. AB - The presence of soft tissue defects in the hand indicates serious traumatic damage that may compromise the systems involved in movement, circulation or touch and therefore jeopardize functional rehabilitation. This overview highlights the significance and the various causes of soft tissue defects. Several types are distinguished. Selection criteria for various flap procedures are outlined with reference to the need for elevation of the hand, the necessity for early movement, adequate wound drainage, and range of motion therapy. The characteristics required of flap tissue are described, such as surface characteristics, ability to restore sense of touch, cosmetic appearance, ability to close deep volume defects, and potential for revascularization of adjacent tissue. Finally, commonly used, selected flaps are presented with notes on their advantages, disadvantages, and modifications, the techniques required and the indications for each. PMID- 2189225 TI - [Reconstructive surgical procedures in scaphoid pseudarthrosis]. AB - Operative procedures for application in scaphoid nonunion are limited by secondary changes of wrist and carpus. The choice of treatment is determined by the degree of vascularization of the fragments. Bony union can be achieved by means of an autogenous free bone graft if there is adequate vascularization of at least one fragment. In the case of extensive impairment of the blood supply, a bone graft on a vascular pedicle is recommended. The postoperative stability of the fragments is of decisive importance for consolidation of the nonunion. The localization and orientation of the nonunion and the extent to which the blood supply is impaired determine the choice of treatment. The standard methods of operation are demonstrated. Our results and experience with the techniques of Matti-Russe I (86 cases), Russe II (18 cases), the Pechlaner-Hussl vascular pedicle bone transplant (35 cases) and the Herbert screw (18 cases) are reported. PMID- 2189226 TI - [Current status of the treatment of distal radius fracture]. AB - The problems encountered in the treatment of fractures of the distal radius lie in the frequent redislocation even after correct reduction. The ASIF classification should be used for a fracture-oriented therapeutic approach. Therefore, only fractures that are not dislocated should be treated conservatively. The majority of fractures require closed or open reduction followed by internal fixation. Articular fractures, in particular, require precise reduction of the articular surface. Following the reduction the fractures should be stabilized, usually with Kirschner wires. The more severe fractures- especially those falling in C1-C3 according to the ASIF classification--can be adequately treated by open reduction with a dorsal or volar approach and subsequent stabilization with the T plate, most often combined with other methods of internal fixation. Open fractures and complex traumas of the upper extremity should be treated by means of a fixateur externe for 2-4 weeks, followed by a change of treatment; the basic decision is usually between internal fixation with plates and further conservative treatment alone. The relatively poor long-term results obtained with treatment of distal radial fractures require that therapeutic guidelines be elaborated for the treatment of these fractures. PMID- 2189227 TI - [Nerve compression syndromes of the elbow and hand]. AB - The importance of nerve compression syndrome in the upper extremity for making a diagnosis or differential diagnosis in orthopedics, surgery, especially hand surgery, and neurology is evident. We review the characteristics of this entity, demonstrate the pathophysiological findings, and stress their importance on the diagnosis, therapy, indications for operation, and operative techniques in our patients. With special regard to the topographic anatomy each of these nerve compression syndromes of the elbow and the wrist region is demonstrated systematically and consequences are discussed for surgical therapy. PMID- 2189228 TI - [Clinical aspects and surgical treatment of Dupuytren contracture]. AB - The etiology of Dupuytren's contracture is still not clear. Many theories have been proposed, but no basic data are currently available that would make it possible to treat Dupuytren's contracture by other methods than surgical intervention. The surgical technique used in our clinic is described, and a postoperative treatment is also outlined. This paper is designed to propose an acceptable technique for practicing trauma and hand surgeons. PMID- 2189229 TI - Late effects of poliomyelitis--a review of osteogenic capacity. AB - A review of 283 patients with late effects of poliomyelitis affecting the limbs revealed no evidence of heterotopic new bone formation, or of greater than normal callus/new bone formation around fractures and osteotomies. It is suggested, in contradiction to the published tradition, that poliomyelitis does not encourage the formation of new bone to any significant extent. PMID- 2189230 TI - Post-marketing drug surveillance--concepts, insights and applications. AB - At the present drug approval process consists of preclinical animal testing, followed by three phases of clinical testing. Phase I is usually conducted on non patient volunteers; phase II involves administration of the drug to a small number of selected patients; and phase III is the final premarketing test of the drug's safety and efficacy. These trials have major limitations, such as restricted patient populations, limited duration of patient exposure, and limited patient numbers. Considerable information remains unknown after the end of phase III testing, including: less common adverse effects; delayed adverse effects; efficacy and toxicity in types of patient usually excluded from premarketing testing, e.g. children, pregnant women and old people; efficacy and toxicity in patients with other illnesses and/or ingesting other drugs; efficacy and toxicity relative to other drugs used for the same purpose; efficacy and toxicity when used for indications other than those initially tested; the toxic effects of a massive overdose; physicians' prescribing habits, etc. The attempt to obtain this information after marketing is postmarketing drug surveillance. PMID- 2189231 TI - Milurit's place in therapy. AB - After a brief review of the history of allopurinol therapy the mechanism of action, interactions with other drugs, side-effects, indications and contra indications of Milurit (100 mg allopurinol per tab, EGIS Pharmaceuticals, Budapest) in adults and children, and the dosage of the drug have been discussed. It has been emphasized that allopurinol is an effective but not the sole means in the treatment of clinical processes accompanied by hyperuricaemia. The adequate choice of a drug in a given indication field not only improves the therapeutic results but prevents the development of one part of the side-effects such as among others the severe allopurinol hypersensitivity syndrome which often has a lethal outcome. PMID- 2189232 TI - Monoclonal antibodies: new diagnostic and therapeutic means in acute leukaemias. AB - The monoclonal antibodies have had a major role in the recent years' development of the diagnostic methods of acute leukaemia. It was by means of these antibodies that the exact mechanism of the differentiation of the different cell lines could be learned a new therapy- and prognosis-orientated leukaemic classifications could be worked out. With the reasonable application of the monoclonal antibodies in more than 99% of the cases the cell line-age and maturity of the dominant cell type of acute leukaemia may be identified today even in cases of aberrant antigen expression. By means of these antibodies clinical relapse may be forecasted in certain cases and minimal residual disease may be demonstrated as well. The therapeutic systemic application of the monoclonal antibodies has yielded only temporary results but in case of bone marrow transplantation their in vitro application is promising since they are capable of eliminating both the T cells and the residual leukaemic cells of the transplant and, as a result, have a role in the prevention of the development of "graft versus host" disease and leukaemic relapse. Monoclonal antibodies are used in acute leukaemia as a routine diagnostic method while their therapeutic application is still at an early stage of investigation. PMID- 2189233 TI - Adult mortality in developing countries. PMID- 2189234 TI - Fine needle aspiration cytology in the diagnosis of Bancroftian filariasis. PMID- 2189235 TI - A stable, oligosymptomatic malaria focus in Thailand. AB - Blood from most of the 250 residents of a non-migratory farming village in south eastern Thailand was visually examined for malaria parasites monthly for 2 years. Nearly 97% of the population had at least one (median = 5) patent Plasmodium falciparum infection per year; 72% had one due to P. vivax (median = 1). This contrasted with a slide positivity rate of 17% calculated from 12 months of passive case detection before the study began. Children 1-9 years old had the highest mean monthly prevalence (51%) and highest geometric mean density (10/500 white blood cells) of P. falciparum. Fewer than half the expected number of mixed infections were found but these were more common at high densities of P. falciparum. Individuals over 19 years old comprised 52% of the population but accounted for only 18% of P. vivax and 32% of P. falciparum gametocytaemias. Fever rates were marginally higher in those below 10 years old (8%) but occurred with equal frequency in those with patent infections or negative. The spleen rate (89% stage 1) was 24% in those under 15 years old and 7% in those older. No malaria mortality was seen P. falciparum cases treated for 10 d with quinine+tetracycline (QT) cleared the infection as often as those given one dose of mefloquine+sulfadoxine+pyrimethamine (MSP); both treatments reduced densities in cases not cured. Apparently unsupervised compliance was no better with MSP than with QT. The role played by hyperendemic, cryptic foci in Asian epidemics of malaria may have been underestimated. PMID- 2189236 TI - HIV, HBV, delta-agent and Treponema pallidum infections in two rural African areas. AB - In order to compare the seroepidemiology of human immunodeficiency virus (HIV), hepatitis B virus, delta agent and Treponema pallidum infections in two rural populations living in north Uganda (Kitgum district) and in central Burundi (Butezi, Ruyigi region), 448 sera were tested for HBS-Ag, HBS-Ab, and anti-HIV antibodies and screened for syphilis using the T. pallidum haemagglutination (TPHA) test. HBS-Ag positive sera were also tested for anti-delta antibodies. Overall seropositivity rates in healthy subjects, outpatients and inpatients (non AIDS) were 14.2% and 9.5% in Kitgum district and Butezi, respectively. The prevalence of HBS-Ag and HBS-Ab ranged from 10.0% to 15.6% and from 66.2% to 68.9%, respectively. In north Uganda the rates of anti-delta positivity were 3.1% in the overall population and 30.6% in the HBS-Ag positive subjects. No serum obtained in Butezi was anti-delta positive. In Ugandan people, 64.0% of anti-HIV positive and 25.8% of anti-HIV negative patients were also TPHA-positive (P less than 0.01). For Butezi the corresponding figures were 21.4% and 1.6% respectively (P less than 0.04). On the contrary, no correlation was found between either anti HIV or TPHA positives and seropositivity for B and delta hepatitis serological markers. The study demonstrated an association between seropositivities for HIV and T. pallidum (TPHA), suggesting common patterns of transmission. On the contrary, no association seemed to exist between HBV and HIV infections. PMID- 2189237 TI - Autoantibodies and tropical infections. AB - Autoantibodies against diverse autoantigens have long been known to exist in the sera of several tropical infections. The introduction of monoclonal antibody technology has allowed immortalization of autoantibody secreting B-lymphocytes and subsequent analysis of these autoantibodies. This paper discusses the current literature on the induction, origins, significance and analysis of autoantibodies. PMID- 2189238 TI - Sciapodes in tropical medicine. PMID- 2189239 TI - Espundia named by Raimondi in 1874. PMID- 2189240 TI - Highly efficient dry season transmission of malaria in Thailand. AB - Man-biting collections were made for 7 consecutive nights per month for 24 months at 2 sites in a Thai village regularly treated with DDT and fenitrothion yet hyperendemic for Plasmodium falciparum and P. vivax. Only Anopheles dirus was incriminated as a vector: 1.6% were infective and 2.4% were infected (median numbers of oocysts = 3.5). Transmission occurred within the village, which was located in groves of rubber and fruit trees, during the dry months of November to May only, when rates of parity (64%) and biting (2/man-night) were higher than during the monsoon (38% and 0.8%/man-night). Vectorial capacity and inoculation rates surged and then fell during 30 d at the end of the monsoon, quickly reinitiating transmission. Sporozoite species were identified using indirect fluorescent antibody tests or enzyme-linked immunosorbent assays: 76% were P. falciparum, compared to 78% of gametocytes; one mosquito was infected with both species. Vector survival and inoculation rates differed between similar sites 800 m apart. Dry season breeding occurred at the bottom of a deep, concrete-lined well. Much of the natural forest habitat of An. dirus in south-eastern Thailand that was once destroyed for farming is now being replaced with orchards; this ecological change may reintroduce malaria to a wide area. PMID- 2189241 TI - Seasonal fluctuation of Plasmodium falciparum gametocytaemia. AB - Two numerically minor components of Plasmodium falciparum prevalence- gametocytaemia and trophozoite densities greater than 99/500 white blood cells- displayed an annual cycle that reflected the seasonal abundance of infective Anopheles dirus at a hyperendemic focus in Thailand, even though the gross monthly prevalence for combined ages remained stable. Gametocyte prevalence rose more than 300% within 30 d after the capture of the dry season's first infective mosquito, remained at about 8% until the beginning of the monsoon 7 months later, then fell within 60 d to about 2%. The number of cases with a high density of trophozoites behaved similarly. These periodic fluctuations represented changes in incidence, at least half of which appeared to be due to superinfection. Almost 49% of all gametocyte carriers were older than 14 years, but nearly all gametocyte densities greater than 20/500 white blood cells were in children. These observations, as well as the calculated efficiency of human infectivity, imply that superinfection of adults may contribute significantly to transmission in semi-immune populations. PMID- 2189242 TI - Microepidemiology, the key to the control of parasitic infections. PMID- 2189243 TI - Malaria infection during pregnancy. PMID- 2189244 TI - The relationship between splenomegaly and antibody to the circumsporozoite protein of Plasmodium falciparum in two groups of women with high and low enlarged spleen rates in Madang, Papua New Guinea. AB - The objective of this study was to determine the prevalence of antibodies recognizing the circumsporozoite (CS) protein of Plasmodium by an enzyme-linked immunosorbent assay, in 2 subpopulations of women with significantly different enlarged spleen rates but similar exposure to malaria, on the north coast of Papua New Guinea. Antibody levels of immunoglobulin G (IgG) antibody to CS protein in the high and low spleen rate groups were similar (56.2% and 55.1%) but there was a significant difference in IgM (29.6% and 16.7%). In neither group did antibodies increase with parity (age). In both groups a high level of either IgG or IgM antibody to CS protein was associated with a high spleen rate and women with hyper-reactive malarious splenomegaly were more likely to be positive for both. Lower parasite rates were associated only with increased IgM antibody titres. High levels of antibody to blood-stage parasites were also present in the high spleen rate group, suggesting that antibodies to the CS protein were not protective. It is considered that cell-mediated immunity may be deficient in women with persistent splenomegaly. PMID- 2189245 TI - Sensitivity to chloroquine in vivo and in vitro of Plasmodium falciparum in Sokoto, Nigeria. PMID- 2189246 TI - Double-blind studies with mefloquine alone and in combination with sulfadoxine pyrimethamine in 120 adults and 120 children with falciparum malaria in Vietnam. AB - In 120 adult Vietnamese patients with uncomplicated falciparum malaria the efficacy of, and tolerance to, mefloquine (M) vs the combination of mefloquine + sulfadoxine + pyrimethamine (MSP) was studied in a double-blind, randomized comparative trial with chloroquine. Also, a double-blind dose finding study of MSP was performed in 120 Vietnamese children with uncomplicated falciparum malaria. In the adults the mean parasite clearance time with M was 3.8 d and with MSP 3.6 d. Defervescence occurred in 2.9 and 3.0 d respectively for M and MSP. There was a 36.8% resistance rate in 38 patients treated with chloroquine. 96% of the children were sensitive or showed a delayed RI response. The lowest dose of MSP (10 mg/kg M + 20 mg/kg S + 1.0 mg/kg P, 1 tablet Fansimef) was as effective as 1.5-2x this dose in children weighing 23-30 kg. Side effects were mild, except for vomiting which required alternative therapy in 4 patients. PMID- 2189247 TI - Short-term oral cinchona alkaloids regimens for treatment of falciparum malaria in Madagascar. PMID- 2189249 TI - Use of total parasite DNA probes for the direct detection of Trypanosoma cruzi and Trypanosoma rangeli in domicilliary Rhodnius prolixus. PMID- 2189248 TI - Proguanil-sulphonamide for malaria prophylaxis. AB - There are few safe, effective chemoprophylactic regimens for preventing Plasmodium falciparum infection in south-east Asia. In two randomized placebo controlled trials, combinations of proguanil and sulphonamide were tested for chemoprophylactic activity in schoolchildren, aged 6-15 years, living near the Thai-Burmese border. Proguanil at an equivalent adult dose of 200 mg/d was combined with sulphafurazole (= sulfisoxazole) at 25 mg/kg/d or sulphamethoxazole at 25 and 10 mg/kg/d. Combinations of daily proguanil/sulphafurazole and proguanil/sulphamethoxazole were equally effective (greater than 75%) against both falciparum and vivax malaria when the sulphonamide component was used at 25 mg/kg/d. Proguanil and sulphamethoxazole at 10 mg/kg/d was ineffective. Approximately 1% of the children had sulphonamide-related skin rashes which resolved when treatment stopped. Proguanil/sulphonamide is a possible alternative chemoprophylactic regimen in areas with multiple drug-resistant P. falciparum. PMID- 2189250 TI - Inflammatory fibroid polyp of the small intestine: ultrastructural and immunohistochemical observations. AB - The ultrastructural and immunohistochemical features of a primary tumor of the ileum showing the classic histologic features of an inflammatory fibroid polyp (IFP) of the gastrointestinal tract are presented. Ultrastructurally the proliferating cells showed a combination of fibroblastic and histiocytic features, with abundant rough endoplasmic reticulum and active production of collagen in many of the cells and long, dendritic cytoplasmic projections with large cytoplasmic vacuoles containing remnants of phagocytosed cellular debris in others. Immunohistochemical studies showed strong cytoplasmic positivity in the proliferating cells with vimentin antibodies and scattered positivity with muramidase. Additional findings include the ultrastructural demonstration of oligocilia and occasional primitive intercellular junctions. The findings in this case suggest that IFP may represent a proliferation of primitive submucosal stromal cells exhibiting incomplete fibrohistiocytic differentiation. PMID- 2189251 TI - Ultrastructural changes of tubular basement membranes in immunologic renal tubular lesions in humans. AB - Ultrastructural changes in the tubular basement membrane (TBM) of 65 renal biopsy specimens from patients with nephropathies or transplant rejection were examined for their potential relationship to deposits observed along the TBM by immunofluorescence (IF). The TBM showed various alterations: irregularities with thickening, lamellation, duplication, and clear spaces. Granular vesicles or inclusions were present inside the thickened TBM. The morphologic changes of the TBM occurred regardless of the severity of rejection of transplants and the type of deposits observed on IF. Electron-dense deposits inside or along the TBM were not found in cases of linear deposits, however. Although these changes were not strictly specific to tubular immune diseases, they could reflect a reaction of the TBM to immune complexes or deposits of antibodies to TBM with degeneration of tubular epithelial cells and sometimes regeneration of a new TBM. PMID- 2189252 TI - Paramesangial destructive lesions in immunoglobulin A nephritis. AB - Paramesangial lesions leading to segmental extracapillary damage were observed in the glomeruli of immunoglobulin A nephritis. Subepithelial accumulation of proteinaceous materials from the mesangium could result in the degeneration and exfoliation of podocytes, apparently with subsequent formation of segmental extracapillary lesions or adhesion to Bowman's capsule (or both). Paramesangial destructive lesions may be initiated by the overloading of the mesangial pathway in glomerular inflammation. PMID- 2189253 TI - [The horizontal patellar dislocation]. AB - The horizontal dislocation of the patella is a very rare event and little described in literature. On the occasion of a 35 years old motor car driver accident mechanism an therapeutic management are discussed. PMID- 2189254 TI - Phenotypic characterization of normal and neoplastic canine endothelial cells by lectin histochemistry. AB - Cell surface glycoconjugate expression of endothelial cells in canine cutaneous hemangiomas and hemangiosarcomas was compared to normal cutaneous endothelial cells using eight different lectins (with and without neuraminidase pretreatment) in an indirect immunoperoxidase technique. Direct comparison of lectin binding pattern of neoplastic endothelial cells with adjacent normal endothelial cells revealed minor changes in the binding intensity of several lectins (enhanced: Wheat germ agglutinin [WGA]; reduced: Griffonia simplicifolia-I [GS-I], Ricinus communis agglutinin-I [RCA-I], Soybean agglutinin after neuraminidase pretreatment [Neu-SBA], and Wheat germ agglutinin after neuraminidase treatment [Neu-WGA]). Neoplastic endothelial cells in some tumors exhibited varying binding of Ulex europaeus agglutinin-I (UEA-I; not binding to normal canine endothelial cells) and no Soybean agglutinin (SBA) binding (variably binding to normal endothelial cells in small cutaneous vessels). Lectin binding of neoplastic cells was rather heterogenous within one tumor compared to the uniform binding pattern of normal endothelial cells. These lectin binding studies demonstrate the phenotypic heterogeneity of neoplastic endothelial cells, indicating changes of cell surface glycosylation during neoplastic transformation. PMID- 2189255 TI - Enterocecocolitis associated with intraepithelial Campylobacter-like bacteria in rabbits (Oryctolagus cuniculus). AB - We examined 28 suckling, weanling, and young adult rabbits with lethargy, inappetence, and mucinous, semifluid feces. Sixteen of the rabbits had intestinal lesions. In eight of these rabbits, the primary changes were multifocal to diffuse epithelial proliferation and accumulation of lymphocytes, macrophages, or both in the lamina propria of the small intestine, cecum, and sacculated colon. In two of these rabbits, the accumulation of macrophages in the lamina propria was extensive. The other eight rabbits had erosive and suppurative cecocolitis, and four of the rabbits with proliferative lesions also had suppurative cecocolitis. In Warthin-Starry-stained sections of affected intestine, curved or spiral bacteria were visible within degenerated or hyperplastic epithelium, in luminal exudate, or in both. Such organisms were sparse or not found in the other 12 rabbits, which did not have intestinal lesions. The bacteria ultrastructurally resembled intraepithelial Campylobacter-like bacteria previously observed in proliferative enteritis in a variety of species and in acute typhlitis in young rabbits. In immunofluorescence tests, Campylobacter-like bacteria in epithelial cells, crypt lumina, and in luminal exudates in both proliferative and erosive lesions bound monoclonal antibodies and polyclonal antisera prepared against intracellular bacteria found in proliferative enteritis in pigs, hamsters, and ferrets. These observations indicate that a condition similar to proliferative enteritis of swine, hamsters, and other species also occurs in laboratory rabbits. PMID- 2189256 TI - Disorders of the lower urinary tract in old dogs. PMID- 2189257 TI - Growth-related changes in the pulmonary function of goats. AB - Growth-related changes in pulmonary function values were investigated in 20 healthy French Alpine goats, aged between 20 and 550 days, weighing 7-55 kg. Pulmonary ventilation, mechanics of breathing and arterial oxygen tension were measured using standardized techniques and methods adapted for goats of different body sizes. The Ppl values and the tI/tTOT ratio showed no significant changes with age and body size. The ventilation values (Vt, Ve, mVI and mVE) increased linearly with growth. There was a significant correlation of age and body weight with dynamic lung compliance (Cdyn), total pulmonary resistance (RL), viscous work of breathing (Wvis tot) and minute viscous work (Wvis min) throughout the age range studied. Cdyn, Wvis tot and Wvis min increased and RL decreased with age and body weight. Arterial blood gases (PaO2 and PaCO2) did not show significant changes over the age range studied. Regression equations for each pulmonary function parameter are given with body weight as the independent variable. Data for the mechanics of breathing were compared with those elsewhere for cattle, horses, man and dogs. PMID- 2189259 TI - [Medical support for the Soviet troops in the Budapest operation]. PMID- 2189258 TI - Intracellular processing and immunogenicity of the envelope proteins of human T cell leukemia virus type I that are expressed from recombinant vaccinia viruses. AB - Two types of recombinant vaccinia viruses (VVs) expressing the env gene of the human T-cell leukemia virus type I (HTLV-I) were reported previously. One recombinant VV, WR-proenv1, synthesized the authentic env protein. In the other recombinant VV, WR-env17, the env gene was inserted within the signal sequence of the VV hemagglutinin (HA) gene, so that the reading frame for the env gene was in phase with that for the HA gene. Comparative studies were performed on the mode of expression and processing of the env proteins in relation to their immunogenicity. In WR-env17-infected cells, translation was initiated exclusively from the initiation methionine of the HA to produce nascently the chimeric env protein, including the altered HA signal peptide. Both this altered HA signal peptide and the internalized env signal peptide functioned as insertion signals for the endoplasmic reticulum. Although about half of the nascent chimeric protein was cleaved at the carboxyl terminus of the internalized env signal peptide to produce the authentic env protein, the other half was cleaved at the carboxyl terminus of the altered HA signal peptide alone to synthesize the chimeric protein. These events led to a less efficient transport of the env protein produced by WR-env17 from the rough endoplasmic reticulum to the Golgi apparatus than that of the authentic env protein synthesized by WR-proenv1. The efficiency of the processing and transport of the env protein affected the immunogenicity of these two recombinant VVs. PMID- 2189260 TI - [Problems in the command activities of the evacuation distributing centers during World War II]. PMID- 2189261 TI - [Losses of troop medical personnel in World War II]. PMID- 2189263 TI - [The scientist, pedagogue and organizer of military public health (on the 90th anniversary of the birth of P. P. Goncharov)]. PMID- 2189262 TI - [The importance of middle molecules in assessing the level of endogenous intoxication (a review of the literature)]. PMID- 2189264 TI - [The contribution of the Department of Medical Service Organization and Tactics of the S. M. Kirov Military Medical Academy to the development of military medicine]. PMID- 2189265 TI - [Comparative aspects of transplacental carcinogenesis]. PMID- 2189266 TI - [Immunohistological study of pulmonary adenocarcinoma using monoclonal antibodies]. AB - Immunohistochemical methods were used to identify A2F4 monoclonal antibodies raised by immunization of animals with a human lung adenocarcinoma cell line in 17 lung adenocarcinomas and five pulmonary metastases of other origin. The antigen identified by the antibodies was registered in 53% of lung adenocarcinomas. Localization of the pulmonary antigen was compared with that of the carcinoembryonic antigen. The expression of the antigens proved different. PMID- 2189267 TI - [Procedure for assessing metastases in animal experiments]. PMID- 2189268 TI - [Milestones of the history of the development of the materials-technology basis of oncologic services of the Soviet public health]. PMID- 2189269 TI - [Nutrition and the physical work capacity of young athletes]. PMID- 2189270 TI - [Food substances and the functioning of the cells of the immune system]. PMID- 2189271 TI - [125 years of the general public hospital of the City of Linz--medical highlights]. AB - The culminating points of medicine in the 125-years history of the General Hospital in Linz were described and the significance of these on the development of medicine in upper Austria were presented. PMID- 2189272 TI - [Restenosis following coronary dilatation]. AB - Restenoses following successful coronary angioplasty occur in about 30 to 35% and are the most important limitative factor of this method. The etiology of restenosis is multifactorial. A beneficial effect in reducing restenosis could not be demonstrated for any drug in the clinical stage. First results with the administration of n-3-fatty acids revealed a favourable influence on recurrence. Further on, the value of newer interventional methods on restenosis rate is also uncertain. Thus, the problem of restenosis remains unresolved. PMID- 2189273 TI - [Double stapling technic in anterior rectum resection]. AB - A new stapling technique for anterior resection is described. The "double stapling technique" (a combination of TA 55 and CEEA) provides several advantages. In 12 patients the postoperative course was uneventful. PMID- 2189274 TI - Giant cell arteritis of the breast--a case report. AB - Recently we experienced a case manifested by a lump in both breast that mimicked carcinoma but was found to be a vasculitis of the giant cell type. Our case was characterized histologically by granulomatous arteritis involving small to medium sized arteries of the breast without involvement of the temporal artery. We described the clinical and pathologic features of a case of giant cell arteritis of the breast and reviewed the eight previously reported cases in foreign literature. PMID- 2189275 TI - Twenty-five years of medical graduates in Papua New Guinea. AB - 1989 is the 25th anniversary of the first doctors trained in Papua New Guinea at the Papuan Medical College (PMC). By the end of 1970 PMC had produced 44 doctors. The following year it became the Medical Faculty of the University of Papua New Guinea (UPNG), which had graduated 318 doctors by February 1989. National doctors now make up approximately two-thirds of the total number of doctors in the country. The largest category of national doctors includes those working with the Health Department, but not at headquarters or specialist medical officer (SMO) level. Private practitioners constitute the second largest category, with almost one-fifth of fully registered national doctors. While postgraduate training programs have been established for clinical and public health specialists, vocational training for general practitioners has been mainly ignored. Private practitioners represent a considerable, and growing, manpower resource in urban areas, and ways need to be found to utilize their services in the public sector. 20% of national private practitioners have the M. Med. degree and 24% of those with the M. Med. are currently in private practice. Medical graduates from PMC and UPNG have a good record in postgraduate education: 37 have passed the M. Med., 62 have obtained a postgraduate medical diploma from UPNG and many have obtained overseas postgraduate diplomas and degrees. It is projected that 80% of SMOs will be national doctors within five years. An increased intake of national medical students into the Medical Faculty is needed now if most doctors in the country are to be nationals by the year 2000. PMID- 2189276 TI - [Does the elastic rapid wound dressing Ankerplast Spray modify wound healing?]. AB - It had been tested if the elastic wound-dressing Ankerplast Spray reduces the risk of an infection of wounds, and if any influences could be observed on the formation of scars after spray-sealing of fresh surgical wounds. In a prospective, controlled study of 597 patients 567 could be postoperatively surveyed at all fixed terms of control up to the 56th day. The infection rate of wounds after general surgical operations amounted to a total of 7 per cent. The rate of hypertrophic scars within the control group was with 11 per cent respectively 7 per cent significantly below the rate of 34 per cent of hypertrophic scars within the Spray group. Are fresh surgical operation wounds being sealed with the elastic wound-dressing Ankerplast Spray no influence can be observed on the postoperative risk of wound infections. Hypertrophic scars must be taken in consideration in about 34 per cent. PMID- 2189277 TI - [Our surgical history. Surgical history memorial calendar 1990]. PMID- 2189278 TI - [Surgical problems in AIDS]. AB - A mortality of 41 percent has so far been recorded from 2.779 cases on the AIDS register. Surgical problems were found to arise only in the terminal stage, when gastro-intestinal, anorectal, pulmonary, neurological, and haematological manifestations have to be expected. Surgical intervention is indicated in situations of massive bleeding, perforations, and mechanical ileus. Opportunistic infections have proved to give rise to the development of gall-bladder empyema and CMV-induced ulcerations. The risk of infection run by medical personnel as well as prophylaxis against AIDS infection of people in contact with HIV infected individuals are described in great detail. PMID- 2189279 TI - Further evaluation of an indirect enzyme-linked immunosorbent assay for the diagnosis of bovine tuberculosis. AB - The sensitivity and specificity of an ELISA for the detection of bovine IgG anti Mycobacterium bovis antibodies were 73.6% and 94.1%, respectively, as determined in 53 bacteriologically confirmed tuberculous cattle and 101 healthy cattle from a tuberculosis-free area. In addition, the results of ELISA and tuberculin tests in 149 cattle were compared with those of subsequent necropsy studies. Both tests failed to detect 2 animals with tuberculous lesions and positive culture; 3/12 cattle with M. bovis isolation and no lesions, and 2/7 with atypical mycobacterial infection reacted to tuberculin, but none had antibodies; in 128 cattle with neither lesions nor mycobacterial isolation, 6 were tuberculin reactors and 7 others had antibodies. Negative results were obtained by ELISA in 21/22 paratuberculous cattle. Antibodies were not detected in 88.9% to 96.4% of 697 cattle from two tuberculin negative herds of an endemic area. In a herd with proved M. bovis infection, distribution of seropositive animals in tuberculin and non-tuberculin reactors was similar. Antibody responses to cutaneous tuberculin stimuli were observed in 4 experimentally infected cattle, but only in 2/10 healthy controls after repeated PPD stimuli. Nine controls which had either received a single tuberculin dose or none showed no increase in antibody levels. The low sensitivity of this ELISA limits its usefulness as a diagnostic tool for bovine tuberculosis eradication campaigns. However, it could be helpful in epidemiological surveillance if its efficiency to identify infected herds is demonstrated. PMID- 2189280 TI - Prevention of cardiovascular risk in women. A new concern for the obstetrician/gynecologist. AB - Cardiovascular disease is the leading cause of death in American women, accounting for nearly half a million deaths annually. While most of these women are postmenopausal, data from the Bogalusa Heart Study have shown that fatty streak formation begins early in life, perhaps even in childhood. Successful risk intervention is best initiated early in the process, before the clinical manifestations of disease become apparent. Several major risk factors for cardiovascular disease--elevated cholesterol, elevated blood pressure, and cigarette smoking--are amenable to intervention. The critical role of cholesterol in the pathogenesis of cardiovascular disease, and the impact of even small fluctuations of important subfractions on CV risk have been demonstrated in numerous epidemiologic and clinical studies. A sensitive predictor of cardiovascular risk appears to be the high-density lipoprotein (HDL) cholesterol fraction, which is considered cardioprotective if elevated and a significant independent risk factor if decreased. Reductions in HDL have been documented following the use of even low-dose oral contraceptives containing progestins of high androgenic activity. Elevated LDL cholesterol may be an independent risk factor for CV disease in women. Hence, changes in the LDL/HDL ratio may be more sensitive predictors of change in CV risk. Major risk factors for CV disease in women are outlined with specific reference to the effects of oral contraceptives on lipoproteins. PMID- 2189281 TI - The selectivity of a new progestin. AB - Norgestimate is a new progestin developed for use with ethinyl estradiol as a combination oral contraceptive. It binds to rabbit uterine progestational receptors and in the oral form stimulates a progestational endometrial effect in rabbits. Norgestimate also exerts a direct effect on target organs, stimulating the endometrium in rabbits when injected directly into the uterine horn and inhibiting luteinizing hormone release from rat pituitary cells in culture. Like other progestins, norgestimate inhibits ovulation in several species and estrogen induced vaginal cornification in ovariectomized rats, but it is not estrogenic. Unlike other progestins, including levonorgestrel and gestodene, norgestimate is relatively free of androgenic activity. Norgestimate's affinity for the androgen receptor is very poor (0.003 x dihydrotestosterone [DHT]), even poorer than that of progesterone (0.005 x DHT). In sharp contrast are the marked affinities of levonorgestrel (0.220 x DHT) and gestodene (0.154 x DHT) for that receptor. The selectivity of norgestimate at receptor level is demonstrated clearly by its highly favorable androgen-to-progestin binding ratio. Norgestimate is similar to progesterone in not significantly stimulating ventral prostate growth in immature rats, whereas levonorgestrel, gestodene, and desogestrel are significantly androgenic in this model. Further evidence of norgestimate's minimal androgenicity is its lack of affinity for human sex hormone binding globulin in vitro. In conclusion, these preclinical studies, consistent with clinical studies, demonstrate the progestational efficacy and selectivity of norgestimate. PMID- 2189282 TI - Efficacy and clinical profile of a new oral contraceptive containing norgestimate. U.S. clinical trials. AB - The search for a highly selective progestin that exerts a potent and targeted progestational response with minimal or absent androgenic effect has paralleled investigation into the possible impact of these agents on cardiovascular disease in women. Such a progestin, norgestimate (NGM), in a dose of 250 micrograms, has been combined with ethinyl estradiol (EE) 35 micrograms in a new oral contraceptive (OC), Ortho-Cyclen or Cilest. Results of two long-term, multicentric clinical trials demonstrate that this formulation is comparable in efficacy to the norgestrel-containing OC Lo/Ovral. There were no statistically significant differences in pregnancy rate, and both OCs were well-tolerated in a large and diverse study population. In several areas, however, the inherently lower androgenicity of the norgestimate OC produced clinical changes compared with the norgestrel formulation. These changes were primarily evident in the more natural menstrual patterns with the norgestimate OC, its less severe impact on the endometrium, and, most important, its positive impact on lipoprotein metabolism. NGM/EE consistently produced statistically significant increases in high density lipoprotein (HDL) and concomitant improvement in the ratio of low density lipoprotein (LDL) to HDL. By cycle 24, this highly predictive parameter of atherosclerotic risk had decreased 7.7% in the NGM/EE group. Conversely, the norgestrel-containing formulation resulted in statistically significant decreases in HDL and increases in the LDL/HDL ratio; by cycle 24, these patients showed an 18.5% increase in the LDL/HDL ratio. All between regimen comparisons of mean changes in the LDL/HDL ratio were statistically significant, from baseline through cycles 3, 6, 12 and 24. PMID- 2189283 TI - Supportive European data on a new oral contraceptive containing norgestimate. AB - Several European studies have been conducted to confirm the efficacy, tolerability, and safety of a new oral contraceptive (OC) combining 250 micrograms norgestimate with 35 micrograms ethinyl estradiol (Ortho-Cyclen or Cilest). In a 12-month multicenter German study of 147 women, treatment with this formulation resulted in no pregnancies, a low incidence of side effects, and excellent cycle control. The drug had no effect on estrogen-mediated fibrin formation nor on the activity of coagulation inhibiting or promoting factors. Similarly, the documented low androgenicity of the highly selective progestational agent norgestimate results in a more positive metabolic profile. Glucose, insulin, and hemoglobin A1c concentrations measured before and after glucose loading were not adversely affected by treatment with the norgestimate containing OC, and all changes were reversible on its discontinuation. In addition, lipid metabolism was positively influenced by the drug. Low-density lipoprotein cholesterol, a known risk factor for cardiovascular disease, was reduced while the cardioprotective lipid fraction, high-density lipoprotein cholesterol, was increased. Clinical trials to determine the OC's effects on coagulation, endocrine function, and carbohydrate and lipid metabolism are reviewed. Also discussed are several studies demonstrating the formulation's unique endometrial effects, which may possibly be related to its low androgenic activity and consequent low incidence of breakthrough bleeding and amenorrhea. PMID- 2189284 TI - The evolution of oral contraceptives. Maximizing efficacy, minimizing risks. AB - No single pharmacologic agent has been more widely studied than the oral contraceptive (OC). Scientific efforts have been directed primarily toward maximizing the benefits of OCs--which remain the most effective, reversible form of birth control--while minimizing their potential risks, specifically thromboembolic disorders and cardiovascular disease. Decreases in the dose of estrogen from the 100 micrograms--150 micrograms levels of the 1960s to the 30 micrograms--50 micrograms formulations of today have been accompanied by dramatic reductions in the risk of thromboembolic events. In healthy women not predisposed to these conditions, the risk of thromboembolism is now considered very small. Similar reductions in the doses of progestin have also resulted in decreases in the incidence of stroke and myocardial infarction. Evidence suggests that not only dose but androgenic activity of a progestin may negatively impact on risk of cardiovascular disease. Thus development of OCs containing a progestin with the least potential for androgenically mediated side effects appears to be advisable. PMID- 2189285 TI - Human placental lactogenic hormone as a parameter for placental function in renal transplanted women. AB - In 13 pregnant women with renal transplants the serum concentration of placental hormones were determined in order to show their ability to predict fetal problems especially placental insufficiency. It is shown that the hPL values were increased because of reduced elimination of hPL, presumably in the renal tubuli. In this study the weight of only one newborn was over the 50th percentile in spite of the fact that all but one had hPL values over the 50th percentile and in even 8 pregnancies the values were over the 95th percentile. In most of the growth-retarded fetus's the ratio between hPL and the weight of the newborns was more complex. It is concluded that in renal transplanted pregnant women, hPL as a parameter for the placental function must be used with reservation and is not able to predict placental insufficiency. PMID- 2189286 TI - In vivo evaluation of bronchoalveolar lavage (BAL) fluid in atopic bronchial asthma, chronic bronchitis and sarcoidosis patients. AB - The intensity of inflammatory response was evaluated in skin test on guinea pig using bronchoalveolar lavage (BAL) fluid obtained from patients with some diseases of the respiratory tract. The results of skin test were verified with activities of proteases in BAL fluid. The study was performed on 24 patients with atopic bronchial asthma, 21 with chronic bronchitis, 13 with sarcoidosis (II phase) and 18 control subjects. All patients were undergoing fiberoptic bronchoscopies and BAL fluid was obtained. The results of skin test on guinea pig using BAL fluid were correlated with the activities of acid and neutral proteases. The highest activity of proteases and intensity of skin reactions were noted in patients with atopic bronchial asthma and sarcoidosis. Authors suggest that the skin test on guinea pig with BAL fluid may be useful tool for total evaluation of inflammatory response in patients with atopic bronchial asthma, chronic bronchitis and sarcoidosis. PMID- 2189287 TI - Pioneers in the profession. William R. Bradley, CIH. PMID- 2189289 TI - Carcinoid tumor presenting as central nervous system symptoms. Case report and review of the literature. AB - Carcinoid tumors are relatively uncommon. They are known for their slow growing behavior and unique symptoms. Patients with carcinoid tumors usually present with signs and symptoms due either to local disease or to the carcinoid syndrome. During the course of these tumors, they tend to metastasize to different sites, including regional lymph nodes, lungs, liver, and bone. They rarely metastasize to the central nervous system (CNS) and very rarely present with signs and symptoms related to CNS metastasis. We report a patient who presented with CNS symptoms and was found to have a pulmonary carcinoid tumor involving the liver and the dura mater. In this article, CNS involvement in carcinoid tumors is discussed, and the literature is reviewed. PMID- 2189288 TI - Neoadjuvant chemotherapy or chemotherapy and endocrine therapy in locally advanced breast carcinoma. A prospective, randomized study. AB - Forty-nine patients with locally advanced breast carcinoma were prospectively randomized to be treated with either CMF or CMF plus T for four courses, both before and after mastectomy. The overall clinical objective remission rate for induction treatment was similar (71% with CMF and 64% with CMF + T). The time to progression or recurrence of the disease was also not significantly different between the two groups. Overall survival was shorter after CMF + T treatment (median value of 41.5 months) than after CMF treatment alone (median value of 79.7 months; p = 0.05). Even after progression or recurrence, survival was shorter for patients receiving CMF + T than those receiving CMF (median values of 7.5 and 17.3 months, respectively; p = 0.09). These results show that the addition of T to CMF in the treatment of locally advanced breast carcinoma, before and after mastectomy, offers no advantage for improving the overall response rate. Moreover, this addition may have an adverse impact on survival in this disease setting. PMID- 2189290 TI - Initial results of phase I/II interstitial thermoradiotherapy for primary advanced and local recurrent tumors. AB - Since January 1986 in a phase I/II study, 45 lesions (30 head and neck, 11 pelvic, and 4 other lesions) in 44 patients (24 men, 20 women; age 18-81 years) received a combination of interstitial Ir-192 radiotherapy (IRT) and interstitial 915 MHz MW hyperthermia (IHT) supplemented by external radiation (ERT). In June 1989, evaluation was performed for lesions with minimum follow-up (FU) of 6 months and FU periods between 6 and 39 months (mean: 16 months, SD +/- 9). The tumors comprised 21 advanced primary (AP) lesions without prior ERT, 18 local recurrent (LR) and 6 local metastatic (LM) lesions with variable prior treatment modes; 24 lesions had received prior ERT between 40 and 70 Gy, 23 chemotherapy and 30 prior surgery. The mean dimensions of 42 lesions were 4.5 X 4.0 X 3.0 (cm3) with tumor volumes ranging from 12 to 135 cm3 (mean: 54 cm3, SD +/- 35); 3 lesions had extensive tumor volumes greater than 225 cm3. IHT was applied immediately prior to and/or after low-dose Ir-192 IRT (20-30 Gy) for 60 min at temperatures between 41 and 44 degrees C. ERT (40-50 Gy) was always given for AP and LM lesions, but variably applied for previously irradiated LR lesions, thereby avoiding the cumulative radiation dose exceeding 110 Gy per site. IRT doses ranged from 17-48 Gy (mean: 26.8 Gy, SD +/- 8) at a dose rate of 25-70 cGy/h (mean: 42 cGy/h, SD +/- 12). Thirty-three lesions received additional ERT of 30-56 Gy (mean: 46.5 Gy, SD +/- 9). Total radiation dose (IRT + ERT dose) ranged from 31 to 82 Gy (mean: 61 Gy, SD +/- 18). The hyperthermia systems of Lund/Buchler 4010 and Clini-Therm Mark VI/IX with thermistor or fiber-optic thermometry devices were employed. Initial response at 3 months FU showed 31 (69%) lesions complete response (CR), 10 (22%) partial response (PR), and 4 (9%) no change (NC). Long-term response of 30 lesions at 12 months FU revealed a total of 27 (90%) with local control (LC) and 3 (10%) in-field recurrences. Six patients died prior to 12 months FU, three with LC and three with progressive disease. So far 10 (22%) patients have developed distant metastases. Acute side effects occurred in 15 lesions (33%) resulting in 12 (27%) long-term complications with 3 lesions (7%) requiring surgery.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2189291 TI - Fine-needle aspiration of non-Hodgkin's lymphoma. Southern blot analysis for antigen receptor, bcl-2, and c-myc gene rearrangements. AB - To determine the utility of Southern blot analysis for fine-needle aspiration samples, the authors prospectively analyzed immunoglobulin, T-cell receptor, c myc, and bcl-2 gene rearrangements in 27 cases of known or suspected lymphoma. Adequate DNA for analysis was obtained from 20 of 27 cases (74%), including 18 of 22 (82%) with non-Hodgkin's lymphoma (NHL). Patients whose tumors showed sclerosis, cellular degeneration, or necrosis yielded inadequate DNA. Of the 18 NHLs with successful Southern blot studies, 17 tumors had a B-cell lineage and one was an adult T-cell leukemia/lymphoma; clonal integration of the human T-cell leukemia virus I (HTLV-I) genome was present in the latter case. Four cases had bcl-2 rearrangements and two had c-myc rearrangements. One patient with follicular small cleaved cell NHL that evolved to a small noncleaved cell NHL had coexisting bcl-2 and c-myc rearrangement in the aspiration specimen of the high grade NHL, suggesting sequential bcl-2 and c-myc activation during the tumor's progression. Southern blot analysis is a useful technique for establishing tumor cell lineage, clonality, and the presence of oncogene rearrangements in fine needle aspiration specimens of NHL. PMID- 2189292 TI - Development of melanosis of uterine cervix after cryotherapy for epithelial dysplasia. A case report and brief review of the literature on pigmented lesions of the cervix. AB - A case of melanosis of the exocervix, which developed within eight months after cryotherapy for epithelial dysplasia, is reported. The literature on pigmented lesions of the cervix is briefly summarized and the importance of biopsy and histologic examination for diagnosis and classification of these lesions is emphasized. PMID- 2189293 TI - Ultrastructural, immunohistochemical, and cytogenetic study of a malignant peripheral neuroectodermal tumor in a patient seropositive for human immunodeficiency virus. AB - A case of malignant peripheral neuroectodermal tumor occurring during the course of a human immunodeficiency virus (HIV) infection is reported. The patient was a male homosexual who presented with a rapidly enlarging tumor of the posterior lower thoracic wall. By light microscopic examination the tumor was a small cell tumor showing occasional structures suggestive of Homer-Wright rosettes. The strong positivity for neuron-specific enolase and the neurosecretory granules indicated the neural differentiation of the tumor. Its precise nature was shown cytogenetically by the presence of the t(11;22) translocation, which distinguished it from the classical neuroblastoma. PMID- 2189294 TI - Gangrenous herpetic whitlow in a human immunodeficiency virus-positive patient. AB - An unusual case of a gangrenous herpetic whitlow is reported. The patient, a 37 year-old man with a ten-year history of intravenous drug abuse, was antibody positive for human immunodeficiency virus. Progressive, extremely painful paronychia of the left third and fourth fingers gradually developed, which persisted despite a variety of treatment protocols, including antibiotics and radiotherapy, ultimately necessitating amputation of the distal portions of the digits. Characteristic herpes-type intranuclear inclusions within epidermal cells were identified in histologic sections of the specimen. Immunohistochemistry using rabbit antihuman herpes virus antibody confirmed the diagnosis. This apparently represents the first documented case of herpetic gangrene in an immunocompromised patient. PMID- 2189295 TI - Congenital toxoplasmosis. The Toxoplasmosis Study Group. PMID- 2189296 TI - Childhood injuries in the United States. Division of Injury Control, Center for Environmental Health and Injury Control, Centers for Disease Control. PMID- 2189297 TI - Childhood drowning and near-drowning in the United States. AB - More than 2000 children drown each year; in some states drowning is considered the leading cause of death for children under the age of 5 years. Many survivors of near-drowning have permanent neurologic disability. There are two distinct high risk groups: children under 5 years of age and boys aged 15 to 19 years. Most drownings in the former group occur in residential pools. Among survivors, the clinical course is bimodal; intact survival and survival with severe permanent disability are the most likely outcomes. The outcome of an immersion event is determined within a few minutes of the onset of immersion, mandating an emphasis on primary prevention. A requirement for pool fencing is the most promising such strategy and could be implemented soon. Training in cardiopulmonary resuscitation and (for older children) alcohol abuse prevention programs may be valuable adjuncts. PMID- 2189298 TI - Violent death and injury in US children and adolescents. AB - Violence, including homicide, child abuse and neglect, and assault by peers and others, causes over 2000 deaths a year to US children aged 0 to 19 years. Homicide is a leading cause of death for US children and adolescents, and so a major cause of years of potential life lost. Infantile and adolescent patterns of homicide are recognized: child abuse by parents characterizes the former; gunshots and other assaults by peers characterize the latter. Nonfatal violent injury is far more prevalent than the fatalities. Reliable estimates indicate that each year close to 1 million female adolescents are sexually assaulted, and more than 1.5 million children and adolescents are abused by the adults responsible for them. Adolescents experience violent crimes at extremely high rates. Risk factors for violent injury are recognized. The most consistent include male sex (except for sexual abuse) and urban residence. Despite the toll of violence, surprisingly little is known about its origins and means to prevent it. The only prevention approach that has been both well evaluated and of apparent benefit is the home health visitor for prevention of child abuse in infants of young, impoverished, unmarried primiparous women. Many other approaches are plausible, promising, and/or being implemented, and these require thorough trial and evaluation. Research on numerous aspects of the precursors and correlates of violence against children is also needed. PMID- 2189299 TI - The treatment of hyponatremia: first, do no harm. PMID- 2189300 TI - Long-term neurologic outcome in psychogenic water drinkers with severe symptomatic hyponatremia: the effect of rapid correction. AB - PURPOSE: The purpose of our study was to ascertain the safety of rapidly correcting acute symptomatic hyponatremia in psychogenic water drinkers, particularly in regard to any delayed adverse neurologic sequelae. PATIENTS AND METHODS: We reviewed the medical records of all known psychogenic water drinkers (34) in our hospital from 1977 to 1989. Using seizure as a marker of severity, we identified 13 patients having a total of 27 episodes associated with severe hyponatremia. We evaluated the charts of those patients in detail to assess the mode of treatment, rate of correction, and long-term neurologic outcome. None of the patients experienced respiratory arrest before treatment, which was initiated within 2 hours of seizure. RESULTS: For all 27 episodes, the initial serum sodium level (mean +/- SE) was 110.9 +/- 1.2 mmol/L, and the rate of correction (mean +/ SE) was 1.65 +/- 0.2 mmol/L/hour. All but one episode were corrected "rapidly" (initial correction rate of 0.7 or more mmol/L/hour) to 120 to 130 mmol/L within 12 hours. The absolute change in the serum sodium level was 15.1 +/- 1.2 mmol/L in 12 hours, 21.6 +/- 1.4 mmol/L in 24 hours, and 25.9 +/- 1.4 mmol/L in 48 hours. In no instance did therapy induce hypernatremia. All patients recovered immediately after treatment. There was no clinical or radiologic evidence of adverse neurologic sequelae immediately after treatment or after 6 years of follow-up. CONCLUSION: In this series of male psychogenic water drinkers, early "rapid" correction of acute symptomatic hyponatremia by raising the serum sodium level 15 mmol/L in 12 hours while maintaining an absolute change in the serum sodium level of 26 mmol/L within 48 hours produced no long-term neurologic sequelae. PMID- 2189301 TI - Theophylline toxicity: clinical features of 116 consecutive cases. AB - PURPOSE: To examine the predisposing factors, clinical and laboratory characteristics, management, course, and outcome of consecutive cases of theophylline toxicity in an outpatient setting. PATIENTS AND METHODS: Toxicology records and hospital charts of consecutive patients with a serum theophylline concentration (STC) greater than 30 mg/L (167 mumol/L) identified in the emergency departments (EDS) of a University Medical Center and a Veterans Administration Medical Center were reviewed. RESULTS: Ten percent and 2.8% of 5,557 consecutive STCs measured in the EDs over 2 years were greater than 20 mg/L (111 mumol/L) and greater than 30 mg/L (167 mumol/L), respectively. One hundred sixteen cases with STC greater than 30 mg/L were identified. Fourteen (12%) and 102 (88%) were due to acute overdose and chronic overmedication, respectively. Principal predisposing factors included patient and/or physician dosing errors and conditions or medications that reduce theophylline clearance. One or more toxic manifestations were present in 109 (94%) cases. Fifty percent of patients had mild toxicity, 38% had moderate toxicity, and 7% had severe or life threatening toxicity. Seven (6%) patients died when STC was still in the toxic range and/or as a result of toxicity. Acute overdose was associated with higher peak STC (p less than 0.001), younger age (p less than 0.01), and greater mortality (p less than 0.05) than chronic overmedication. Peak STC correlated significantly with the severity of toxicity for patients with acute overdose (p less than 0.01) but not for patients with chronic overmedication. All three patients with acute overdose and fatal toxicity had peak STCs greater than 100 mg/L (555 mumol/L) and fulminant toxicity, whereas the four patients with chronic overmedication who died during toxicity had peak STCs in the 40 to 60 mg/L (222 to 333 mumol/L) range and most died of respiratory failure rather than directly from toxicity. Patients with acute overdose who had the delayed onset of severe or life-threatening toxicity and/or died from toxicity were accurately identified using previously published criteria for prophylactic charcoal hemoperfusion. In contrast, the predictive value of the criteria applied to patients with chronic overmedication was poor. Two patients with acute overdose underwent charcoal hemoperfusion, but died. No patient with chronic overmedication received charcoal hemoperfusion. CONCLUSION: Toxic-range STCs are relatively common in the ED population, occur primarily as a result of patient and physician dosing errors, and cause a broad range of toxic manifestations of varying severity. Peak STC correlates with the severity of toxicity and outcome for acute overdose but not chronic overmedication intoxication. Previously published criteria for prophylactic charcoal hemoperfusion accurately identify patients with acute overdose but not patients with chronic overmedication at risk for serious complications and death. PMID- 2189302 TI - Outcome of first-trimester exposure to low-dose methotrexate in eight patients with rheumatic disease. AB - PURPOSE: Methotrexate (MTX), when used to treat malignancy or psoriasis, has been implicated in anecdotal reports as a teratogen or abortifacient in the first trimester of pregnancy. We are unaware of any previous reports that describe the course of gestation and the effect on subsequent offspring in patients treated with low-dose oral MTX for rheumatoid arthritis, and therefore present our experience. PATIENTS AND METHODS: We report on eight women experiencing 10 pregnancies. Mean number of weeks of gestation while taking MTX was 7.5 (range 2 to 20 weeks). Outcome of pregnancies included five full-term babies (FTB), three spontaneous abortions (SAB), and two elective abortions. RESULTS: There were no significant differences in either the FTB or SAB group when considering risk factors including smoking, alcohol, concomitant medications, and age. One of three in the SAB group had recurrent abortions prior to MTX therapy. All five of the FTB group had uncomplicated pregnancies and deliveries. All offspring were of normal height and weight at birth with no physical abnormalities. All children reached growth, development, and intellectual stages normally, and their present mean age is 11.5 years. No observed learning disabilities or medical abnormalities have occurred in any of these children. CONCLUSION: In this uncontrolled study we failed to demonstrate tertogenicity of MTX. However, the possibility of abortion due to MTX use remains. PMID- 2189304 TI - Plasma immunoreactive endothelin in essential hypertension. AB - PURPOSE: Endothelin plays a role in the regulation of vascular tonus. Therefore, it has been hypothesized that increased production or release of endothelin or both may contribute to the pathogenesis of hypertension. To assess any changes in the plasma endothelin concentration in essential hypertension, plasma immunoreactive endothelin concentrations were measured in patients with essential hypertension. PATIENTS AND METHODS: We measured plasma immunoreactive endothelin concentrations in 42 subjects with essential hypertension, 12 subjects with borderline hypertension, and 25 normotensive control subjects. RESULTS: The concentrations were higher in hypertensive patients than in borderline hypertensive patients and normotensive subjects (both p less than 0.05), although values in normotensives and hypertensives overlapped. Reverse-phase high performance liquid chromatography (HPLC) and radioimmuno-assay showed two components of plasma endothelin, one corresponding to synthetic endothelin-1 (1 21) and the other corresponding to synthetic big endothelin (human, 1-38). The HPLC profile of plasma endothelin of hypertensive patients was the same as that of normotensive subjects. Hypertensives with reduced glomerular filtration rates or increased serum creatinine levels had higher plasma endothelin concentrations than hypertensive patients as a whole (p less than 0.05). Mean blood pressure and serum creatinine levels were correlated to plasma endothelin in the hypertensives. Correlation was negative between glomerular filtration rate and the endothelin level in the hypertensives. CONCLUSION: Plasma endothelin was elevated in many hypertensive patients with severe hypertension or renal involvement. Its major components were endothelin-1 and big endothelin. PMID- 2189303 TI - Chromogranin A in familial pheochromocytoma: diagnostic screening value, prediction of tumor mass, and post-resection kinetics indicating two-compartment distribution. AB - PURPOSE: Chromogranin A, co-released with catecholamines from the adrenal medullary and sympathetic neuronal vesicles, is elevated in plasma from patients with pheochromocytoma. We assessed its diagnostic screening value, its plasma level in correlation with tumor mass, and its disposition kinetics in familial pheochromocytoma and sporadic pheochromocytoma. PATIENTS AND METHODS: The sensitivity and specificity of chromogranin A's diagnostic value for pheochromocytoma were established through one kindred with familial pheochromocytoma associated with von Hippel-Lindau syndrome (13 available members) and in seven subjects with sporadic pheochromocytoma. Serial postoperative plasma samples were also obtained (5 minutes to 4 days) from eight subjects with pheochromocytoma in order to study chromogranin A post-resection kinetics. Chromogranin A was measured by radioimmunoassay based on purified pheochromocytoma chromogranin A. RESULTS: In this kindred, elevations of chromogranin A (greater than 52 ng/mL) were sensitive (83%, five of six) and specific (100%, 10 of 10) in detecting familial pheochromocytoma; these diagnostic values comparable to those achieved by conventional evaluations for pheochromocytoma, such as urinary catecholamines, urinary catecholamine metabolites or imaging methods. Elevated levels of plasma chromogranin A specifically indicated pheochromocytoma, rather than von Hippel-Lindau syndrome gene carrier status. In 13 preoperative subjects with either familial or sporadic pheochromocytoma, plasma chromogranin A concentration predicted tumor size (r = 0.81, p less than 0.01). The change in chromogranin A plasma concentration after pheochromocytoma resection best fit a two-compartment model, with an initial rapid half-life time of 16 minutes, followed by a longer half-life time of 520 minutes. The model also predicted a 23.8:1 compartmental ratio of extravascular/intravascular chromogranin A, suggesting substantial tissue sequestration or binding of chromogranin A. CONCLUSIONS: (1) Plasma chromogranin A is a valuable (sensitive and specific) diagnostic tool in detecting both familial and sporadic pheochromocytoma. (2) The concentration of plasma chromogranin A predicts the size of the pheochromocytoma. (3) Chromogranin A post resection kinetics suggest extravascular sequestration of chromogranin A. PMID- 2189305 TI - Effect of granulocyte-macrophage colony-stimulating factor on neutropenia and related morbidity induced by myelotoxic chemotherapy. AB - PURPOSE: A phase Ib/II clinical study was undertaken to assess the efficacy of recombinant human (rh) granulocyte-macrophage colony-stimulating (GM-CSF) factor in attenuating neutropenia and associated morbidity caused by high-dose anticancer chemotherapy administered in the presence or absence of autologous bone marrow support. PATIENTS AND METHODS: Twenty-two patients with various solid tumors and lymphoid neoplasias were treated with a single daily subcutaneous dose of rh GM-CSF (250 micrograms/m2) 48 hours after receiving a second cycle of highly myelotoxic chemotherapy for a period of 10 days. Within-subject comparisons on neutropenia-related clinical and laboratory variables were made with data obtained from the same patients after they received the first neutropenia-inducing cycle of identical chemotherapy in the absence of GM-CSF. RESULTS: GM-CSF was active in neutropenic patients because it significantly increased the neutrophilic nadir, reduced the time of relevant neutropenia, and reduced the duration of a patient's hospital stay and the necessity for parenteral antibiotics. No significant toxicity was encountered with subcutaneous GM-CSF treatment. CONCLUSION: Although GM-CSF was shown to significantly reduce chemotherapy-associated morbidity in patients receiving myelotoxic cancer chemotherapy, additional studies are needed to assess whether the use of GM-CSF in anticancer chemotherapy will allow an increase in the dosage level, leading to improved response rates and survival among cancer patients. PMID- 2189306 TI - Biochemical basis of thyroid hormone action in the heart. AB - Thyroid hormone-induced changes in cardiac function have been recognized for over 150 years; however, the biochemical basis of triiodothyronine (T3) action in the heart has been intensely investigated only during the last two decades. T3 induced changes in cardiac function can result from direct or indirect T3 effects. Direct T3 effects result from T3 action in the heart itself and are mediated by nuclear or extranuclear mechanisms. Extranuclear T3 effects, which occur independent of nuclear T3 receptor binding and increases in protein synthesis, influence primarily the transport of amino acids, sugars, and calcium across the cell membrane. Nuclear T3 effects are mediated by the binding of T3 to specific nuclear receptor proteins, which results in increased transcription of T3-responsive cardiac genes. The T3 receptor is a member of the ligand-activated transcription factor family and is encoded by cellular erythroblastosis A (c-erb A) genes. The c-erb A protein is the cellular homologue of the viral erythroblastosis A (v-erb A) protein, which causes red cell leukemia in chickens. Currently, three T3-binding isoforms of the c-erb protein and two non-T3-binding nuclear proteins that exert positive and negative effects on T3-responsive cardiac genes have been identified. T3 increases the heart transcription of the myosin heavy chain (MHC) alpha gene and decreases the transcription of the MHC beta gene, leading to an increase of myosin V1 and a decrease in myosin V3 isoenzymes. Myosin V1, which is composed of two MHC alpha, has a higher myosin ATPase activity than myosin V3, which contains two MHC beta. The globular head of myosin V1, with its higher ATPase activity, leads to a more rapid movement of the globular head of myosin along the thin filament, resulting in an increased velocity of contraction. T3 also leads to an increase in the speed of diastolic relaxation, which is caused by the more efficient pumping of the calcium ATPase of the sarcoplasmic reticulum (SR). This T3 effect results from T3-induced increases in the level of the mRNA coding for the SR calcium ATPase protein, leading to an increased number of calcium ATPase pump units in the SR. Overall, thyroid hormone leads to an increase in ATP consumption in the heart. In addition, less chemical energy of ATP is used for contractile purposes and more of it goes toward heat production, which causes a decreased efficiency of the contractile process in the hyperthyroid heart. PMID- 2189307 TI - Thyroid hormone and the cardiovascular system. AB - To understand the pathophysiology of thyroid heart disease, it is necessary to recognize that thyroid hormone has effects on both the peripheral circulation and the myocardium. One of the earliest responses to thyroid hormone administration is a decline in systemic vascular resistance and an increase in cardiac output and cardiac contractility. In many ways, this response is similar to the cardiovascular response to exercise and is associated with increased left ventricular work. The majority of cardiac adaptations to changes in thyroid function are physiologic; however, certain patients do demonstrate clinical evidence of cardiac disease. Atrial arrhythmias, limitations in exercise tolerance, and congestive heart failure are reported to occur as a result of hyperthyroidism and are more common in older patients. Thyroid hormone also plays an important role in the regulation of blood pressure. Diastolic hypertension is a common accompaniment of hypothyroidism. By understanding the mechanisms by which thyroid hormone affects both the peripheral circulation as well as the myocardium, it is possible to predict the clinical response to the treatment of various thyroid disease states. PMID- 2189308 TI - Recognition and management of cardiovascular disease related to thyroid dysfunction. AB - Hypothyroidism and hyperthyroidism are both associated with clinically significant cardiovascular derangements. In hypothyroidism, these include pericardial effusion, heart failure, and the complex interrelationship between hypothyroidism and ischemic heart disease. Cardiovascular disorders associated with hyperthyroidism include atrial tachyarrhythmias, mitral valve dysfunction, and heart failure. Although these usually occur in individuals with intrinsic heart disease, thyroid dysfunction alone rarely causes serious but reversible cardiovascular dysfunction. Patients with commonly encountered cardiac disorders, e.g., idiopathic cardiomyopathy and atrial fibrillation, should be screened for potentially contributing subclinical thyroid diseases. In patients with heart failure and hypothyroidism, initial management should focus on diagnosis and optimal management of any primary cardiac disease, whereas in hyperthyroidism, aggressive measures to control excess thyroid hormone action should generally have the highest priority. PMID- 2189309 TI - Catecholamine-thyroid hormone interactions and the cardiovascular manifestations of hyperthyroidism. AB - The spectrum of classic symptoms of hyperthyroidism suggests that in addition to the effects of increased thyroid hormone, affecting various organ systems, there is also a hyperadrenergic state. Despite this clinical impression, direct measures of serum levels of catecholamines and their urinary metabolites demonstrate values that are equal to or less than normal. In contrast, the hypothyroid patient who clinically manifests signs of decreased adrenergic stimulation can be expected to have increased levels of epinephrine, norepinephrine, and its metabolites. This review discusses possible mechanisms to explain this seeming paradox. Treatment of hyperthyroidism includes the rapid reversal of many of the adrenergic symptoms with use of beta-blocking drugs. Return to a clinically and chemically euthyroid state, however, requires antithyroid therapy accomplished over a longer period of time. A knowledge of the interaction of the cardiovascular and extracardiovascular manifestations of hyperthyroidism and the role of the adrenergic nervous system is important in the rational management of these patients. PMID- 2189310 TI - Disulfiram treatment of alcoholism. AB - PURPOSE: For 40 years, disulfiram has been the alcohol-aversive drug used most frequently by American physicians in the treatment of alcohol dependency disorders. We reviewed the clinical literature regarding the risks, benefits, indications, and efficacy of this controversial drug and summarized current knowledge of this therapy. CONCLUSIONS: Disulfiram will produce an aversive reaction with ethanol, usually at a dose between 250 mg/day and 500 mg/day, although some patients may not have an aversive reaction at this level. Cardiac, hepatic, and neurologic toxicity can also occur within this dosage range. If disulfiram is to be used, the patient must clearly understand the risks of drinking while taking the drug, and the physician and patient must agree about the need for continued clinical supervision and monitoring for efficacy and side effects. The physician must also recognize that disulfiram is only an adjunctive therapy and that continued support, supervision, and other therapeutic measures are required. Disulfiram is probably effective in reducing the frequency of alcohol consumption in the compliant patient over the short term (e.g., 6 months). Certain subgroups of patients, such as those who are older, those who are more socially stable, and those who are well-motivated, may experience a beneficial effect for longer periods. The drug may be most effective in reducing short-term alcohol consumption when the compliance of the patient is supervised, although consideration of this kind of therapy includes the practical problems of supervising the patient and concerns that the supervising person may be placed in a difficult position. Prescription of disulfiram without accompanying education, counseling, and concomitant alcoholism therapy is not beneficial. Disulfiram has no proven effect on the long-term outcome of alcoholism. PMID- 2189311 TI - Hereditary angioedema: its diagnostic and management perspectives. AB - Although hereditary angioedema accounts for only a small fraction of all cases of angioedema, it is the most common genetically linked clinical disorder caused by the deficiency of a protein associated with complement activation. Attacks may be complicated by incapacitating cutaneous swelling, life-threatening upper airway impediment, and severe gastrointestinal colic. Recent physicochemical and genetic studies have contributed significantly to our understanding of the structure of the inhibitor protein. Measurement of serum C4 titer is an efficacious screening test. Normal levels during symptomatic periods rule out the diagnosis, whereas decreased levels warrant determination of C1 esterase inhibitor titer by immunoassay or functional assay. The functional assay is necessary to ascertain the genetic variant form. The importance of making the correct diagnosis cannot be overemphasized. It can avert potentially fatal consequences, such as upper airway obstruction and unnecessary abdominal surgery. The application of short term preventive measures can avoid complications associated with trauma. Finally, abatement or elimination of symptoms in patients with incessant and disabling attacks can be attained by long-term therapy with currently available attenuated androgens. PMID- 2189312 TI - Abdominal pain, total intravascular hemolysis, and death in a 53-year-old woman. PMID- 2189313 TI - Nonwheezing bronchial asthma diagnosed by methacholine challenge. PMID- 2189314 TI - Partners in care. 1973. PMID- 2189315 TI - HMB-45 antibody reactivity in pigmented lesions of the conjunctiva. AB - Conjunctival pigmented lesions, including ten compound nevi, three subepithelial nevi, two acquired melanoses, and six melanomas, were examined histologically and immunohistochemically to determine the specificity of mouse monoclonal HMB-45 antibody for these lesions. Eleven of 13 nevi, two of two acquired melanoses, and six of six melanomas stained with this antibody. Conjunctival melanomas showed intense and diffuse cytoplasmic staining; compound nevi and subepithelial nevi showed less intense but diffuse reaction. There was strong staining in melanocytic cells at the junction of the epithelium and substantia propria in compound nevi and acquired melanoses. Unlike skin nevi, conjunctival nevi show HMB-45 reactivity in their stromal components. Immunoreactivity to HMB-45 does not distinguish benign from atypical or malignant melanocytic lesions of the conjunctiva. PMID- 2189316 TI - Primate trabeculectomies with 5-fluorouracil collagen implants. AB - Bilateral trabeculectomies were performed on four normal cynomolgus monkeys. Highly purified bovine skin collagen implants with either 1 mg of 5-fluorouracil or physiologic saline (one each per monkey by randomized, masked assignment) were sutured under the scleral flaps. The randomization code was not broken until all clinical and histopathologic observations had been completed. Six weeks postoperatively, the 5-fluorouracil-treated eyes had more deeply open internal trabeculectomy ostia than the control eyes; however, the intraocular pressures were indistinguishable, the filtering blebs were only minimally different, and half of each group had trace or mild anterior subcapsular lenticular changes. Histologically, a multinucleated foreign body giant cell reaction was evident in all of the collagen implants, but the 5-fluorouracil-treated eyes had less vigorous or delayed reactions compared to the control eyes. The collagen implant appears to be a poor drug delivery system in this model of glaucoma filtering surgery, because it incites a granulomatous inflammatory reaction. PMID- 2189317 TI - Potentially fatal asthma. PMID- 2189318 TI - Angiotensin converting enzyme inhibitors and the allergist. AB - Angiotensin converting enzyme inhibitors (ACEI) are used widely in the treatment of both hypertension and congestive heart failure. Although usually well tolerated, these medications may produce side effects that may be encountered by the allergist, including cough, angioedema, and rhinitis symptoms. The severity of ACEI-induced cough may vary, and is associated with increased bronchial hyperreactivity in some (but not all) patients as judged by methacholine sensitivity. Angiotensin converting enzyme inhibitor-induced cough may have its onset from one day to 12 months after initiation of therapy, and is not dose dependent. Angioedema caused by ACEI is usually mild and clears with discontinuation of the drug, however cases requiring intubation and tracheostomy have been reported. The mechanism of ACEI-induced cough remains unclear, but could be in part due to accumulation of substances whose degradation may also be impeded by ACEI, such as substance P, bradykinins, and/or prostaglandins. Knowledge of the side effects produced by this class of medication may help patients avoid unnecessary, costly, and often invasive diagnostic evaluations. PMID- 2189319 TI - Evaluation of symptom relief, nasal airflow, nasal cytology, and acceptability of two formulations of flunisolide nasal spray in patients with perennial allergic rhinitis. AB - A new formulation of intranasal flunisolide containing less propylene glycol was compared with the original formulation for efficacy and acceptability in more than 200 patients with symptoms of perennial allergic rhinitis. In this multicenter, randomized, double-blind, parallel group study, symptomatic patients were treated with either the new or the original formulation of 0.025% solution of intranasal flunisolide for 4 weeks to provide 200 micrograms flunisolide daily. Both formulations were highly effective in decreasing symptom scores as evident from patient diary reports before and after treatment (P less than .001). Similarly, nasal airflow was improved with each treatment as measured by anterior rhinomanometry (P less than .0002) and the number of patients with nasal eosinophilia decreased (P less than .01). Finally, fewer patients using the new formulation reported nasal burning or stinging and the acceptability rating of the new formulation was higher. PMID- 2189320 TI - [The value of diagnostic endoscopy in the treatment of intestinal polyps in the child]. AB - The polyps of the digestive tract, with the exception of the juvenile ones, are not often found in children. Out of 762 endoscopies paediatric patients carried out, 31 were seen to be affected by digestive polyps, of which 16 were juvenile. The rest belonged to other types, among which 5 adenomas are included. In this paper, clinical aspects are analysed, pointing out also the value of the endoscopy as choice method not only for diagnosis but also for treatment of polyps. PMID- 2189321 TI - [Prevention of bicycle accidents in children]. AB - The preventive measures of bicycle accidents in children, depends on the knowledge of the risk of use of the bicycle by children. In our study, over 50% of severe bicycle accidents had CNS trauma, pointing the need of brain protection. In view of our experience we recommend the teaching of the rules of circulation to children and the necessity of periodic bicycle revisions. PMID- 2189322 TI - [Experience with the impression cytology test for detecting vitamin A deficiency in children]. AB - Impression cytology has been suggested as a relatively simple, cheap, practical and non invasive technique for documenting physiologically significant vitamin A deficiency. The vitamin A status of 41 patients was evaluated by serum retinol concentration by high power liquid chromatography (HPLC) and conjunctival impression cytology was performed on each child. All children with normal vitamin A status had normal conjunctival impression cytology. The sensibility of this method was 100%. However, in the 8 vitamin A deficient patients by impression cytology, only 6 of them showed low serum vitamin A levels. Impression cytology appears to detect preclinical vitamin A deficiency that this technique may by of potential usefulness as a screening tool for preclinical vitamin A deficiency populations. PMID- 2189323 TI - [The current state of Niemann-Pick disease: evaluation of six cases]. AB - Six pediatric patients with Niemann-Pick disease are reported. They have been studied at Hepatology Unit HI "La Paz" (Madrid) in the period of time between 1975-1988. They are one case of type A, one case of type B and four cases of type C. This group of pediatric patients serve us to make a revision of the disease attending to clinical and biochemical classification aspects, diagnosis and treatment. We insist on two aspects: 1) greater importance of enzymatic diagnose for the "Niemann-Pick complex", in view of the overlapping of clinical symptoms, 2) bone-marrow transplantation as therapeutic alternative and its indications. PMID- 2189324 TI - [Multicystic encephalomalacia in twin pregnancies]. AB - Multicystic encephalomalacia (ME) is a rare entity in the pediatric age. In ME brain tissue in substituted by cavities of variable size. ME has different etiologies being asphyxia and circulatory alterations the most important factors. In monozygotic twins there is an increased incidence of structural anomalies than dizygotic twins. We present four twin patients with ME. Three of them had a prenatal dead sibling. The fourth pair of twins had a twin-twin transfusion. We want to stress the utility of brain echography in early diagnosis of ME. PMID- 2189325 TI - [Dietary recommendations and hypercholesteremia in children]. PMID- 2189326 TI - [The demand for emergency services at pediatric hospitals: a study of 4,858 cases treated at the emergency department of a pediatric hospital]. AB - Given the rise in hospital emergencies, a detailed study of the demand for emergency pediatric care is a must. We compiled 4,858 medical records elected at random and gathered data about global activity in the emergency department of pediatric hospital. The demand for emergency pediatric care grows faster than the corresponding population. The higher and lower patient influxes were on Sunday and Wednesday respectively. The peak rate of influx was attained at 8 pm, whereas the low happened at 6 am. Pediatric emergencies diminish with age and are less frequent in girls than in boys. Only 15.86% of the patients had been referred by a physician. Fever and accidents were the most frequent reason for consultation. Ear, nose and throat diseases are at the top and double in frequency the bronchopulmonary sickness. Analyses were done in 12% of the cases, radiographs were taken in 23% of the patients and 68.58% of the casualties were taken were care of without any of these means. The visit was finished in a mean of 1.99 hours, a swift performance. Of all the cases studied, 93.4% were discharged and 5.3% were admitted to the same hospital. Our data confirm and complete the one published fragmentarily in the Spanish literature. We emphasize that a primary pediatrician could have spared the emergency department a lot of work. We conclude that accessible continuous care must be offered in order to transcend patchwork in following growth and development through pediatric emergency rooms. PMID- 2189327 TI - [A multicenter study of ambulatory pediatric service]. PMID- 2189329 TI - [Laboratory diagnosis of respiratory syncytial virus infection]. AB - We study 18 children with acute respiratory infection diagnosed early by direct immunofluorescence (DIF) using monoclonal antibodies to synticial respiratory virus (SRV). Antibodies to adenovirus, influenza virus A and B, parainfluenza virus 1, 2 and 3, mycoplasma, Q fever, herpes and cytomegalovirus (CMV) are also studied. We consider that in most cases the diagnosis of infections caused by SRV cannot be established by complement fixation, and should be accompanied by some antigen detection technique. Direct immunofluorescence facilitates the early detection of SRV in most cases before the appearance of antibodies to this virus. Only one of the 18 patients with positive DIF presented antibodies to SRV. PMID- 2189328 TI - [Flunarizine and dihydroergotamine in the treatment of migraine in children]. AB - We administer during 6 months in randomised way dihydroergotamine or flunarizine to 50 children affects of classical or common migraine. A significative improvement was estimated in frequency, intensity and duration of their crisis in 87% with dihydroergotamine and 79% with flunarizine, without significative differences from one to other. Dihydroergotamine was specially effective in children with vegetative lability. The secondary effects, 12% with dihydroergotamine and 20% with flunarizine, were trivial and advantageous even, without the necessity of stop the treatment in not any case. PMID- 2189330 TI - [Rheumatic fever: clinical and therapeutic aspects]. AB - From 1974 to 1987 we have diagnosed thirty three patients with rheumatic fever. The age of onset ranged from three to sixteen years with a mean age of nine years and six months. Carditis was the most frequent major criteria (27/33) followed by arthritis (14/33) and Sydenham's chorea (6/33). All the patients with carditis had the mitral valve affected. The usual treatment in the acute phase was penicillin and aspirin. The prophylaxis recommended to the patients was penicillin G benzatine every 21 days if they had carditis and every 28 days if they didn't. Two patients allergic to penicillin are receiving erythromycin. We have observed that the incidence of rheumatic fever has remained unchanged that the age of onset increased and that the antiinflammatory drug of choice in most patients with carditis is aspirin. PMID- 2189331 TI - [Chronic lymphocytic thyroiditis in children and adolescents: apropos of 51 cases]. AB - Fifty one patients were diagnosed as having chronic lymphocytic thyroiditis, according the Fisher's criteria. Their ages range was between 4.2 to 17.8 years. According to their basal values of T4 and TSH, they were divided into the following groups: 1. Euthyroids (n = 14), with both thyroxine and thyrotrophin, within normal limits. 2. Hypothyroid group (n = 37), subdivided into: 2.a normal T4 and elevated TSH (n = 18); 2.b low T4 with high TSH (n = 19). The TRH test showed an exaggerated TSH response in four cases in the euthyroid group, and in all the cases of hypothyroid group. This test carried out at the time of diagnosis, can show up alterations in thyroid function, which are not detected by basal assessments of T4 and TSH. The most frequent isotope scan image, was that of a unilateral decreased uptake in one lobe. We consider it to be of graf interest, given that the fine biopsies performed in this area were all positive. PMID- 2189332 TI - [Captopril treatment of neonatal arterial hypertension]. AB - Captopril, an orally active angiotensin I-converting inhibitor, is an effective drug in the treatment of hypertension in adults and children. The use in newborn infants has been, nevertheless, short. We report five cases of hypertension in newborn infants poorly responsive to large doses of other potent antihypertensive agents: furosemide, propanolol and hydralazine. We have got a reduction in mean blood pressure in three cases, with doses of 0.1-0.2 mg/kg/day for a time lesser than a month. Another patient had a reduction with high doses (5 mg/kg), showing increase in mean serum urea, creatinin, potassium and phosphorus levels. This effect disappeared after captopril was discontinued. We suggest the use of captopril in hypertension non-responsive to other antihypertensive agents, mainly in those of renovascular cause. PMID- 2189333 TI - [Late spontaneous revascularization of an internal mammary graft onto the anterior interventricular artery]. AB - The authors report a case of internal mammary artery graft anastomosed to the left anterior descending coronary artery (LADC) which was found to be non functional in the early post-operative period (one month) but second catheterization at one year revealed the graft to be patent with thrombosis of the LADC. This case shows the flow adjustment possibilities of internal mammary artery graft. PMID- 2189334 TI - [Exploratory thoracotomy of necessity in surgery of bronchial cancer]. AB - The survey conducted by the French Language Society of Thoracic and Cardiovascular Surgery collected a total of 2,962 exploratory thoracotomies for lung cancer performed over a period of 10 years. Over the same period, 25,291 operations were performed for lung resection, so that the mean rate of exploratory thoracotomy was therefore 11.7%. The rate of exploratory thoracotomy varied from one unit to another (2.7% to 45.8%) and appeared to be virtually independent of the operative activity. It has continued to decrease over time, which is even more significant in view of the fact that the operative activity has increased in all of the units. The local and regional spread of the tumour represents the principal reason for non-resection (79% of cases); it was less common in units with a high operative activity (72%) than in other units (84%) especially when the mediastinal lymph nodes were involved. The major thoracic surgery units also appear to be distinguished by a greater audacity, as well as an increased failure rate in the case of tumour spread to the trachea. The risk of exploratory thoracotomy is considerable as it was responsible for death in 3% of cases. A better radiological and clinical assessment, rather than the use of mediastinoscopy should avoid 2% of these useless explorations. The subsequent course of these patients barely concerns the surgeon: it is rapidly unfavourable and the rare long-term survivals (2% at five years) are not sufficient to justify operation at any cost. PMID- 2189335 TI - [Giant esophageal fibrovascular polyp. Apropos of a case]. AB - Fibrovascular polyps, together with eleiomyomas, constitute the great majority of rare benign tumors of the oesophagus. Their size and their frequently high level of attachment sometimes give them a spectacular clinical presentation. The hazards involved in the interpretation of radiological and endoscopic data account for frequent mistakes in their diagnosis. The determination of the pedicle site defines the choice of the surgical approach. A diagnostic error and the choice of an incorrect approach are the two main causes of therapeutic difficulties. PMID- 2189336 TI - [Iatrogenic tracheal and left bronchial stenoses. Uncommon complication of Carlens tube. Apropos of a case surgically treated in a single stage]. AB - Independent synchronized ventilation of each lung is a new form of management of severe predominantly pulmonary lesions unaliteral. Mechanical ventilatory assistance is also used via a cuffed double lumen tube (Carlens tube). Tracheal stenosis and bronchial stenosis may result from injury caused by respiratory assistance given via this tube. The etiology of the lesion appears to be direct pressure erosion of the tracheal and bronchial walls by the cuff with subsequent repair by scarformation. These lesions were present in a young man. This report describes the surgical treatment: the double stenosis was treated by resection with end-to-end anastomosis with an excellent result. PMID- 2189337 TI - [Rupture of the diaphragm of late manifestation]. AB - Twenty one cases of delayed diagnosis of ruptured diaphragm caused by closed trauma are reported: 14 on the left side and 7 on the right side. The clinical signs and the modes of presentation are non-specific. Although the history of thoraco-abdominal trauma and the chest x-ray are sufficient to establish the diagnosis of rupture of the left hemidiaphragm, they can only suggest the diagnosis in cases of righ-sided rupture. The mechanism of rupture is more often due to sudden reflex contraction of the diaphragm against a closed glottis than to excessive abdominal pressure caused by the trauma. Diaphragmatic rupture due to closed trauma causes large tears exposing the patient to a low risk of strangulation of intestinal structures in contrast with ruptures due to a penetrating injury, which causes small tears. The diaphragmatic domes must be systematically explored during laparotomy or thoracotomy performed for thoraco abdominal trauma. PMID- 2189338 TI - [Cardiac tumor mass. Diagnostic and therapeutic approach. Apropos of 46 cases]. AB - The authors analyse a series of 46 operated intracardiac tumours (0.4% of all cases of cardiac surgery). The predominant symptoms were episodes of heart failure and pseudo-valvular disease. Peripheral emboli and pericardiac syndromes with tamponade occurred more rarely and constituted surgical emergencies. Non invasive investigations, dominated by echocardiography, allow early diagnosis. The majority of tumours were situated in the left atrium and consisted, histologically, of myxomas, the surgical treatment of which consists of wide excision of the pedicle. Malignant tumours (17.7%) were dominated by cardiac sarcomas. When possible, extensive resection of these tumours may improve the chances of medium-term and long-term survival. The operative mortality was 8.8%. The delayed mortality was due to malignant tumours (17.3%). Myxomas must be followed in the long-term by systematic echocardiography. The authors observed 11% of recurrences occurring after a interval of 12 to 144 months (3 cases). PMID- 2189339 TI - [A case of left ventricle-right atrium defect caused by nonpenetrating injury of the thorax]. AB - A rare observation of left ventricular-right atrial defect is reported in a 17 year old boy, victim of a serious car accident. The elements of diagnosis and the congenital or traumatic origin of this defect were discussed. Surgical treatment with application of a patch enssured recovery. PMID- 2189340 TI - Aetiology of nasopharyngeal carcinoma. AB - Nasopharyngeal carcinoma (NPC), a rare tumour in most parts of the world, occurs in high frequencies in China and South East Asia and is particularly high among the Southern Chinese. In certain parts of China the incidence may reach 50 per 10(5) per year while in most other ethnic groups the incidence is very low, e.g. among Caucasians the incidence is less than 1 per 10(5) per year. These marked geographic and racial differences in incidence have stimulated much research into the aetiology of this cancer. Potential aetiological factors will have to explain this 50-100 fold difference in incidence. Both genetic and various environmental factors have been postulated. This paper discusses the role of the Histocompatibility Locus Antigen (HLA), Epstein Barr Virus and chemical carcinogen including salted fish in the development of NPC. PMID- 2189341 TI - Cutaneous carcinogenesis: a review of recent advances in pathogenesis. AB - The clinical spectrum of cutaneous carcinogenesis has not changed substantially. New insights into the pathogenesis of ultraviolet induced lesions have resulted in better understanding of the basic biology of cutaneous tumours. This has evolved into the development of 4 stages in skin carcinogenesis. New problems like Human Immunodeficiency Virus (HIV), associated tumours and ozone depletion are emerging, which will require greater research efforts into preventing a further increase in incidence. PMID- 2189342 TI - Biological modifiers and their role in cancer therapy. AB - Biological modification in cancer therapy involves many different strategies and substances. Bacterial products with established usefulness include BCG, C. parvum and L-Asparaginase. Immunotherapy with such agents has not, however, found general application, although revived interest in 'Coley's mixed toxins' (used earlier this century) paralleled the development of their presumed effector molecules, tumour necrosis factor and lymphotoxin. Many other Cytokines, both natural or recombinant, are now produced on a vast scale following the recent biotechnology revolution. Of these, Alpha Interferons have already proved useful in hairy cell leukaemia, carcinoid tumours, renal cell cancer, Kaposi's sarcoma, chronic granulocytic leukaemia and certain lymphomas, whilst their use as adjuvants or in combination is currently being investigated. More recently, Interleukin-2, which stimulates the clonal expansion of activated T-cells, has shown promise both as a single agent, and when used with lymphokine activated killer (LAK) cells or tumour infiltrating lymphocytes (TILS). A different approach involves the Colony Stimulating Factors such as G-CSF and GM-CSF which reduce the degree and duration of treatment-related myelosuppression, thereby allowing more intensive cytotoxic or radiation therapy, as well as facilitating early recovery following bone marrow transplantation. Monoclonal antibodies have not proved as specific for malignant cells as was originally hoped, but certain tumours, such as lymphoma, are now realistic targets for therapy. Increasingly sophisticated effector mechanisms (e.g. conjugated pro-drugs) and genetically engineered "humanised" monoclonal antibody hybrids present the brightest hopes for the future. Biotherapy, the "fourth modality of cancer treatment" has already assumed its place alongside surgery, radiotherapy and cytotoxic chemotherapy, and will grow in importance as our understanding of the molecular biology of cancer increases in the coming decades. PMID- 2189343 TI - Tumour necrosis factors in clinical practice. AB - The tumour necrosis factors are pleiotropic proteins which have a wide range of biological activities. Tumour necrosis factor-alpha or cachectin is a product of macrophages and is the principal host mediator of septic shock and the cachexia of chronic disease. A related molecule, tumour necrosis factor-beta or lymphotoxin, is produced by T lymphocytes in response to antigen or mitogens. The role of the TNFs in disease processes and in therapy are reviewed. Both agents exert antiproliferative effects on certain tumour cell lines, while normal cells are resistant to these effects. In vivo, they cause haemorrhagic necrosis of certain implantable tumours in mice. Trials of tumour necrosis factor-alpha as an anticancer agent, either singly or in combination with interferon gamma or cytotoxic drugs, are in progress. Understanding the involvement of the tumour necrosis factors in pathological processes may lead to new therapies for endotoxic shock and cancer. PMID- 2189344 TI - Immunotoxins: the potential in cancer treatment. AB - Since its development in 1975, monoclonal antibody (mAb) technology has greatly enhanced our ability to analyse complex antigenic systems as well as improve the sensitivity and speed of many diagnostic tests. In particular, the study of tumour associated antigens using mAbs have revealed that many transformed cell phenotypes have useful markers on their plasma membrane, cytoplasm, or as secreted forms which can be used in developing diagnostic assays. Therapeutic application of these anti-tumour mAbs has however, been slow relative to the research and diagnostic applications. This article will discuss how the therapeutic effectiveness of anti-tumour mAbs can be enhanced by coupling them to drugs, toxins or radionucleids; and review the current advances and problems related to the application of these mAb conjugates. PMID- 2189345 TI - Tumour markers--a diagnostic and therapeutic perspective. AB - A number of chemically diverse substances is associated with the malignant transformation of cells. Though none of these can be said to be wholly specific they are operationally useful and this paper is a selective review of some of them. They arise from exposure of previously cryptic epitopes in membranes and secreted molecules and the amplification of normally small quantities of cellular components, such as oncogenes in chromosomes. Antibodies directed to these tumour markers are opening up new avenues of research, diagnosis and therapy of cancer patients. The use of radioisotope labelled antibodies has become sufficiently sensitive and specific to be useful for decision-making in their clinical management. PMID- 2189346 TI - The myelodysplastic syndromes. AB - The myelodysplastic syndromes are a group of diseases mainly afflicting the elderly of unknown aetiology manifesting with clinical and laboratory manifestations of ineffective haematopoiesis. This review discusses the clinical and morphological features of the syndrome followed by a critical appraisal of the French American British (FAB) group classification. The presenting symptoms are usually non-specific and relate to the peripheral cytopenia(s). The marrow is invariably hyperplastic with peripheral cytopenia(s) together with characteristic trilineage dysplastic morphological changes. Prognostic stratification and treatment are outlined. Lack of effective treatment of this syndrome remains an outstanding problem. PMID- 2189347 TI - Cervical cancer: aetiology, earlier diagnosis and treatment. AB - Cervical cancer which is one of the commonest genital malignancies in women worldwide including Singapore is reviewed. There is a decreased incidence and mortality rate from cervical cancer with well organised population-based screening programmes using cervical smears. Strong evidence exists for a sexually transmitted etiologic agent in cervical cancer. The evidence of an association between Herpes Simplex Virus Type 2 (HSV-2) and certain Human Papillomavirus (HPV) infections especially HPV 16 and HPV 18 in the etiology of cervical cancer is reviewed. Diagnosis of asymptomatic clinically occult lesions is by cervical cone biopsy following colposcopic evaluation of those with abnormal smears. The diagnosis of clinically invasive lesions is made by careful evaluation of the cervix and confirmed by biopsy. Treatment of occult and early clinically lesions is ideally by a spectrum of surgical procedures which are carefully tailored to the extent of the lesion but of advanced cancers mainly with radiation therapy with adjuvant surgery and/or chemotherapy in selected cases. Best results for cervical cancer treatment are obtained when treatment facilities are centralised and treatment performed by experienced individuals who individualise therapy or integrate the use of all therapeutic modalities of surgery, radiation and chemotherapy. PMID- 2189348 TI - Liver transplantation in cancer--a review. AB - Whilst liver transplantation is an accepted therapeutic modality for end stage cirrhosis, its application for hepatic malignancy has remained a controversial issue. This is due to the early experience in several centres of tumour recurrence within the first year. More recently, stringent patient selection criteria have been established to decrease the risk of tumour recurrence. Pre operative assessment including liver biopsy, computerised axial tomography (CT) of both the thorax and abdomen, bone scans and pre-transplant laparotomy are routinely performed to exclude extrahepatic spread. Of the primary tumours, the most common groups are the hepatocellular carcinomas (HCC) and cholangiocarcinomas. A hierarchy of tumours favourable for transplantation exists, with HCC giving the best results, followed by central bile duct carcinoma, cholangiocellular carcinoma (peripheral), and secondaries, in descending order of suitability. With better patient selection based on adequate staging, and the confinement of liver grafting to lymph node negative stages, there has been a marked improvement in survival in otherwise unresectable and mainly untreatable tumours. The improved results support the application of liver grafting for malignancy, and suggest that the often discussed danger of tumour growth enhancement because of immunosuppression may not significantly be present. Despite the risk of tumour recurrence, liver transplantation gives worthwhile survival with the chance of cure for some and in others, considerable palliation with prolonged survival. PMID- 2189349 TI - Current status of treatment for breast cancer. AB - Recent developments in the treatment of early stage breast cancer include mature data from randomised trials that indicate limited surgery with breast irradiation provide comparable survival to total or radical mastectomy. For patients undergoing radical mastectomy while post-operative radiotherapy should not be routine, when more than four axillary lymph nodes are involved at surgery or the primary tumour involves the medial quadrants, then local recurrence rates are significantly reduced by this radiotherapy. Overview statistical metanalyses of data from adjuvant therapy trials has confirmed that cyclophosphamide, methotrexate and 5-fluorouracil chemotherapy reduced the risk of death by 24 +/- 6% compared to controls for premenopausal women. Whereas, administration of tamoxifen for more than one year to postmenopausal women with positive axillary lymph nodes and positive hormone receptor levels resulted in a 18 +/- 4% reduction in mortality. Similar adjuvant treatments in women with negative axillary lymph nodes but other adverse prognostic factors improves disease-free but not as yet overall survival. In advanced disease, the success of hormone manipulation is dependant on the presence and amount of oestrogen and progesterone receptor protein in either the primary breast tumour or a biopsied metastasis. If a response is achieved, this will be complete in 5-20% of patients with a median survival in excess of 18 months for responding patients and 25% remaining alive and disease-free beyond 30 months. Combination chemotherapy for patients with negative hormone receptors or aggressive disease achieve response in 50-60% of patients. Current activity to improve the therapeutic index of chemotherapy include less toxic analogs, priming hormones and high dose chemotherapy. PMID- 2189350 TI - Surgery in Singapore: the Scottish link. AB - The History of Surgery in Singapore is over a hundred years old. The major land marks are, the starting of the Medical School, the rapid development of health and hospital services after the war and the establishment and growth of major specialities and postgraduate education in the last 15 years. This paper traces the significant Scottish influence in the various stages of developmental history of Surgery in Singapore. PMID- 2189351 TI - Eagle's syndrome. Review of the literature and a case report. AB - Eagle's syndrome has received scant attention in both medical and dental literature. The symptoms related to this condition can be confused with those attributed to a wide variety of facial neuralgias. The present case refers to a 46-year-old white woman with the symptomatology of Eagle's syndrome, especially the carotid artery type. PMID- 2189352 TI - Keratoacanthoma versus squamous cell carcinoma of the lower lip. AB - The authors' aim in this study is to discuss and review, from the presentation of a keratoacanthoma case with a clinical diagnosis of squamous cell carcinoma, the clinical and histologic criteria for a differential diagnosis between these two lesions, as well as to analyze the factors presumably involved in keratoacanthoma formation. PMID- 2189353 TI - [Conservative treatment of epidermoid cancer of the anal canal combining radiotherapy and curietherapy. Experience at the Antoine-Lacassagne Center]. AB - From 1973 to 1987, 33 patients aged from 46 to 86 years (25 female, 8 male) were treated for a tumour of the anal canal with radiotherapy and curietherapy. Tumour distribution was 7 T1, 19 T2, 7 T3, and 4 patients were N+. After treatment it was possible to assess 31 patients; 29 were in complete remission, remission was obtained in 2 others following surgery. Tolerance was comparable to other series but 4 patients developed necrosis of the anal canal; 2 patients died under general anesthesia and 1 patient had a radiation injury of the small intestine. The sphincter was conserved in 65 p. cent of cases. Relapse occurred in 8 patients within 6-92 months, and 6 patients developed metastases. Overall survival was 78 p. cent at 3 years and 74 p. cent at 5 and 10 years. Disease-free survival was 65 p. cent at 3 and 5 years and 52 p. cent at 10 years. Our results confirm those of other series using a similar treatment plan. This treatment is difficult to put into practice. Patients must be carefully selected preferably by a team including proctologist, surgeon and radiotherapist. PMID- 2189354 TI - [Portal and mesenteric thrombosis. Etiology, clinical manifestations and treatment]. PMID- 2189355 TI - [What is left of lactose intolerance?]. PMID- 2189356 TI - [Carbohydrate digestion and intestinal function disorders]. PMID- 2189357 TI - [Should a gluten-free diet in celiac disease be followed for ever?]. PMID- 2189358 TI - [Oxalates and the digestive tract]. PMID- 2189359 TI - The assessment of disease aggressivity in stage D2 prostate cancer patients (review). AB - Suppression of androgen levels in blood of stage D2 prostate cancer patients has been the prominent treatment for advanced prostate cancer. However, the duration of hormone sensitivity of prostate tumor is variable. The type of initial response to hormonal treatment, the length of response and patient's survival are in direct association with disease aggressiveness. Recently, an arithmetic formula expressing disease aggressivity was computed using pretreatment values of prostatic acid phosphatase (P.A.P.), alkaline phosphatase (A.P.), degree of tumor differentiation and number of bone metastases. This aggressiveness score was related to disease response and patients outcome receiving hormonal treatments. The use of an arithmetic formula to express disease aggressivity could result in a subdivision of the disease. The identification of the subgroup of stage D2 patients destined not to benefit from hormonal manipulation could change the strategies employed up until today for the treatment of advanced prostate cancer. PMID- 2189360 TI - Stimulatory effect of luteinizing hormone on the development and maintenance of 5 alpha-reduced steroid-producing testicular interstitial cell tumors in Fischer 344 rats. AB - The development and maintenance of testicular interstitial cell (IC) tumors under the conditions of low LH levels were examined in aged Fischer 344 rats, and the enzyme activities for androgen synthesis in the tumors were estimated. Sixty-week old rats received injections of an LH-RH agonist (LH-RHa) for 28 weeks or were subjected to a procedure by which Silastic tubes containing testosterone (T) or estradiol-17 beta (E) were subcutaneously implanted. All 88-week old control animals had bilateral IC tumors, whereas 100% of the T-, E- and LH-RHa-treated rats at week 88 were tumor free. These treated rats showed significantly reduced peripheral LH levels compared to the control animals. No hyperplasia or tumors of the IC were noted in 70-week old animals receiving T for 28 weeks, while all age matched untreated animals showed IC tumors or hyperplasia. The IC tumors in rats 69 weeks of age decreased in size in response to 4-week treatment involving the subcutaneous implantation of tubes containing T. After removal of the tubes, however, the tumors once again increased in size. Reduced and subsequently elevated serum LH levels were also observed with this treatment. These changes in tumor mass volume were mainly due to a change in the tumor cell volume which was possibly related to LH levels, i.e., large cells were predominant under relatively high peripheral LH levels and intermediate cells were predominant under low LH levels. Quantitative analyses of the in vitro products formed from [3H]progesterone and [14C]4-androstenedione in tissue-homogenates revealed a low 17 alpha-hydroxylase activity and a high 5 alpha-reductase activity in the IC tumors compared to those activities in the testicular tissues; in the tumors, low production of T and high production of 5 alpha-metabolites of progesterone were observed. From these data, it seems reasonable to conclude that sufficient levels of LH are essential for the induction of IC tumors or hyperplasia and the maintenance of tumor mass, and that the low production of T in the tumors is due, at least in part, to decreased 17 alpha-hydroxylase and increased 5 alpha reductase activities under active steroidogenesis. PMID- 2189361 TI - Trial of intralesional interferon alfa in the treatment of alopecia areata. AB - Eleven patients with alopecia areata, ranging from patchy disease to alopecia universalis, were treated with intralesional interferon alfa-2 on a selected area of alopecia. Follow-up at 3 months revealed local terminal hair growth in one patient. At 12 months, variable disease activity was seen. Regional lymphadenopathy, a new finding with interferon, was seen in four patients during the treatment. Immunohistochemical studies showed some changes in the inflammatory infiltrates and in HLA-DR expression that may be related to the interferon or to the dynamics of the inflammatory infiltrate in alopecia areata. Interferon, at the dosage and treatment schedule used in our trial, had no significant effect on alopecia areata. PMID- 2189362 TI - Accuracy in the clinical diagnosis of malignant melanoma. AB - The computerized database (1955 through 1982) of the Oncology Section of the Skin and Cancer Unit of New York (NY) University Medical Center includes data on 13,878 lesions. Of these lesions, 214 were diagnosed clinically and histologically as malignant melanoma (MM). An additional 51 lesions, diagnosed clinically as other than MMs, were found histologically to be MM. Seventy-nine lesions were clinically diagnosed as MM but were found histologically to be other entities. An analysis of the clinical diagnostic accuracy showed some improvement over the three periods studied (1955 through 1963, 1964 through 1973, and 1974 through 1982). Although the diagnostic accuracy for the best period (1974 through 1982) was only 64%, the diagnosis of MM was made in 84.5% of the histologically proved cases of MM, reflecting a high degree of sensitivity. PMID- 2189363 TI - A peculiar purple bruise. Necrotizing fasciitis due to a group-A beta-hemolytic streptococci. PMID- 2189364 TI - Changes in cutaneous Kaposi's sarcoma in a patient infected with the human immunodeficiency virus: follow-up to a controlled hyperimmunization trial. PMID- 2189365 TI - Pathogenesis and management of aspergillosis in cystic fibrosis. PMID- 2189366 TI - Management of threadworm infestation during pregnancy. PMID- 2189367 TI - Treatment of acute, episodic asthma in preschool children using intermittent high dose inhaled steroids at home. AB - In a double blind, controlled trial, the effect of high dose beclomethasone dipropionate (750 micrograms three times daily for five days) administered by metered dose inhaler and valved spacer, was compared with placebo, during 70 paired episodes of acute asthma in 24 preschool children. Treatment commenced at home at the first sign of an attack. Parents' blind preference for active treatment was significant. Data from 17 pairs of treatment, however, were affected by interventions such as hospital admission or oral corticosteroid treatment. These events occurred similarly in active and control periods. An intrasubject comparison was made of diary scores from the 18 pairs of episodes in which no intervention occurred in either the active or placebo treatment. Both daytime and night symptoms over the first week of the attack were significantly reduced by active treatment. Intermittent high dose inhaled beclomethasone dipropionate is beneficial in modifying the severity of acute episodic asthma in preschool children able to use a spacer device. PMID- 2189369 TI - The human genome: a prospect for paediatrics. PMID- 2189368 TI - Food and drug reactions, wheezing, and eczema in preterm infants. AB - Allergic reactions were investigated in 777 preterm infants who were randomly assigned to early diet and followed up to 18 months post term. Wheezing or asthma was common (incidence 23%); it was associated with neonatal ventilation, maternal smoking, and a family history of atopy and was unexpectedly reduced in babies born by caesarean section. Even in non-ventilated infants, the incidence of subsequent wheezing was 18%, rising to an estimated 44% (using logistic regression) when the foregoing risk factors (excluding ventilation) were present. Eczema occurred in 151 infants (19%) and was strongly associated with multiple pregnancy (30% incidence in twins or triplets). Reactions to cows' milk (incidence: 4.4% from detailed history; 0.8% confirmed by challenge), other foods (10%), and drugs (5%) were within the range reported in full term infants. Milk and food reactions were associated with multiple pregnancy (19%) and a family history of atopy. Reactions to drugs were least likely to occur in infants who had been ventilated and were on multiple medications in the neonatal period, suggesting that drug tolerance may have developed. We speculate that preterm infants may be a high risk group for asthma and eczema, which could imply an association between atopy and prematurity. PMID- 2189371 TI - [Robert Merle d'Aubigne. 1900-1989]. PMID- 2189370 TI - Choice of sleeping position for infants: possible association with cot death. PMID- 2189372 TI - Primary hepatic lymphoma presenting as intravascular lymphomatosis. AB - A case of primary hepatic lymphoma presenting as intravascular lymphomatosis was diagnosed in a 69-year-old woman who presented with symptoms related to the digestive tract. These symptoms were followed by neurologic disorders, including disturbance of sensation and mentality, and pathologic reflexes suggestive of a broad intracerebral lesion. Computed tomography of the brain showed an ill defined, low-density area in the bilateral parietotemporal lobes. Autopsy revealed a well-circumscribed hepatic tumor, 6 cm in diameter, and scattered hemorrhagic foci in the cerebral cortexes. Microscopically, the hepatic tumor was a diffuse lymphoma, large cell, of the B-cell type. The small vessels of the brain were found to be packed with lymphoma cells, having caused the florid neurologic manifestations. PMID- 2189373 TI - Expression of the 5.1 H11 antigen, a fetal muscle surface antigen, in normal and neoplastic tissue. AB - The monoclonal antibody 5.1 H11 recognizes an antigen on human fetal muscle and on rhabdomyosarcoma cell lines and xenografts that has been shown to be homologous to the neural cell adhesion molecule. To evaluate its range of expression, we used immunoperoxidase staining of fresh frozen-tissue sections to determine monoclonal antibody 5.1 H11 reactivity in normal and neoplastic tissue. Among normal tissue specimens, intense antibody staining was seen in brain and peripheral nerve, and weaker staining in ganglionic elements of colon. In addition to 26 of 29 rhabdomyosarcoma specimens, 5.1 H11 antibody showed reactivity to 9 of 10 Wilms' tumors, 6 of 6 neural tumors, and 4 of 4 gliomas, and with single specimens of ectomesenchymoma, clear-cell sarcoma of kidney, undifferentiated sarcoma of liver, ovarian fibroma, and neurofibroma. We conclude that the monoclonal antibody 5.1 H11 recognizes an antigen present not only on fetal muscle but on normal brain and nerve as well. In addition to rhabdomyosarcoma, a variety of other tumors, most of which have been previously shown to express neural cell adhesion molecule, also appear to express the antigen recognized by 5.1 H11. Our results thus offer additional confirmatory evidence that an epitope of neural cell adhesion molecule is the antigen for 5.1 H11. PMID- 2189374 TI - Development of intrahepatic bile ducts in humans. Possible role of laminin. AB - Laminin, a major extracellular matrix-attachment glycoprotein, may play an important role in the differentiation and migration of epithelial cells during normal development. Therefore, the morphogenesis of bile ducts in human liver of fetuses at sequential gestational ages, neonates, children, and adults was examined by single and double immunohistochemical staining for laminin and for cytokeratins. The latter served as a marker for developing and mature bile duct epithelial cells. A close association was observed between laminin deposition and the differentiating ductal plate cells at the epithelial-mesenchymal interface of portal tracts and during the subsequent migration of ductular structures into the center of portal tracts. Simultaneously, laminin disappeared from the margins of portal tracts, but scattered ductal plate-like structures with laminin remained demonstrable in neonates, children, and even adults. These observations were substantiated by semiquantitative evaluation of laminin at the periphery of portal tracts. Thus, clear evidence is provided that laminin accompanies bile duct epithelial cells during all successive stages of differentiation and migration during the development of the human hepatobiliary system. The persisting ductal plate cells may represent a common stem cell for proliferation of bile ductules and hepatocytes. PMID- 2189375 TI - Primary malignant mesenchymoma of bone. AB - Primary malignant mesenchymoma of bone is a rare neoplasm consisting of two or more unrelated tissue elements other than a fibrosarcomatous component. To our knowledge, only six cases have been reported in the literature. A case of malignant mesenchymoma composed of rhabdomyosarcoma, chondrosarcoma, and osteosarcoma arising within the right acetabulum, resulting in the patient's death 4 months after presentation, is reported, and the literature is reviewed, with a discussion of the similarities to dedifferentiated chondrosarcoma. PMID- 2189376 TI - Clinical and pathologic correlations in patients with periampullary tumors. AB - Perioperative data on 87 patients undergoing pancreatoduodenectomy for periampullary tumors were correlated with pathologic study of operative specimens to identify the accuracy of diagnosis and the factors affecting survival. Accuracy of endoscopic retrograde cholangiopancreatography and computed tomography in locating lesions was 75% and 44%, respectively. Histologic diagnosis before or at the time of resection was available in only 61% of the patients. Carcinoma was correctly diagnosed clinically by the pathologist or the surgeon in 95% (83/87) of patients with 4 patients found to have benign disease on final pathologic examination. Intraoperative diagnosis of site of origin was incorrect in 18% (16/87) of patients. In 28% (23/83) of patients, pathologists identified nodal metastatic disease missed by the surgeon. Survival correlated with nodal and margin status and tumor grade. Tumor size demonstrated no predictive capacity. Although preoperative diagnostic accuracy is less than optimal, surgeons can usually diagnose malignant lesions but more often fail to identify tumor origin and nodal disease. We continue to advocate resection for patients with periampullary lesions thought to be malignant and resectable without a positive histologic diagnosis. PMID- 2189378 TI - Cigarette smoking. A risk factor for cerebral infarction in young adults. AB - To assess the impact of cigarette smoking on stroke in young adults (15 to 45 years old), we compared smoking data from 181 patients with cerebral infarction with that of 307 control subjects matched for age, gender, geographic location, and hospital admission dates. While controlling for these matching variables and hypertension, an analysis based on a conditional logistic regression model indicated that a smoker was 1.6 times more likely to have a cerebral infarction than a non-smoker (95% confidence interval, 1.07 to 2.42). There was a cumulative dose effect with each additional pack-year causing a greater risk of having a cerebral infarction. In fact, after adjusting for all other risk factors, there was a significant quadratic component to the dose-response relationships, with the result that individuals with a larger number of pack-years were invariably the stroke patients. There was no significant difference in smoking status among the various subtypes of cerebral infarction (atherosclerotic, nonatherosclerotic vasculopathy, cardioembolic, hematologic related, undetermined). These data indicate that cigarette smoking is an important risk factor for cerebral infarction in young adults. Risk factor modification through cessation of smoking may reduce the risk of ischemic stroke in young adults. PMID- 2189377 TI - The impact of technology on the management of pancreatic pseudocyst. Fifth annual Samuel Jason Mixter Lecture. AB - The records of 299 patients with 357 admissions for pancreatic pseudocysts seen between 1960 and 1989 were studied; 233 patients underwent operation. The natural history of pancreatic pseudocysts has been clarified by newer technology, such as ultrasonography, computer tomography, amylase isoenzyme measurements, and endoscopic retrograde cholangiopancreatography. All have influenced diagnosis, nonoperative management, and surgical operation. Differences between pancreatic pseudocysts associated with acute pancreatitis in contrast with chronic pancreatitis, and the complications of obstruction, hemorrhage, rupture, pancreatic ascites, infection, and jaundice can now be more rationally treated. Pancreatic pseudocysts and pancreatic ductal changes are now revealed earlier, especially by endoscopic retrograde cholangiopancreatography. Paradoxically, this information has encouraged nonoperative conservative therapy and also larger operations, eg, resection and adjunctive pancreaticojejunostomy. Partial resection of the pancreas together with the pancreatic pseudocysts was performed in 58 (25%) of the 233 patients. Recent technology permits cautious exploration of selective pancreatic pseudocyst drainage percutaneously or transgastroduodenally avoiding laparotomy. PMID- 2189379 TI - The suspension therapy for tabes dorsalis. A case history of a therapeutic fad. AB - The suspension therapy of tabes dorsalis was introduced by Motschutkovsky in 1883, popularized by Charcot and Gilles de la Tourette in 1889, and subsequently rapidly and widely disseminated on the basis of enthusiastic case series. Dissemination was facilitated by endorsements of eminent neurologists, widespread publicity in professional journals and lay press, and the apparent simplicity and safety of the procedure. However, increasingly critical reports appeared, indicating much lower success rates, frequent postprocedure deterioration, and occasional serious complications. The disparity between early and later studies resulted from a placebo effect, from disregard of the natural history of the condition, from misdiagnosis, and from biased observation and reporting. By the end of 1890, the procedure was largely abandoned, despite proponents' attempts to modify the technique or to identify a more responsive subgroup of patients. PMID- 2189380 TI - Impression material consistency and peripheral tissues. AB - The behaviour of three alginate impression materials was tested in vivo by sectioning the peripheries of a series of impressions in a standard manner and measuring the extension in three directions: buccal, lingual and into the depth of the sulcus. The three materials used reacted in accordance with their various consistencies. There were statistically significant differences between all the materials in the inferior measurement, but very few differences in the buccal dimension. Lingually however, one extended significantly further than the other two. It is concluded that the facial tissues, probably muscles, play a restraining role in buccal impression material extension but that the inferior and lingual extensions are more susceptible to the consistency of the material rather than the tissues. This should be carefully considered before selecting a suitable material for impressions. PMID- 2189381 TI - RAS oncogene product expression in normal and malignant oral mucosa. AB - Proto-oncogenes are important in both normal cellular differentiation and in carcinogenesis. The majority of transforming genes belong to the ras family and the ras gene product has been shown to be elevated in some oral carcinomas. RAP-5 monoclonal antibody was used to determine the expression of the p21ras protein in normal and neoplastic oral mucosa in an immunohistological study. The expression of p21ras protein was generally restricted to acanthous cells with strong staining in normal oral mucosa and well-differentiated carcinomas. In contrast, the p21ras protein was not detected in significant amounts in severely dysplastic lesions and poorly differentiated carcinomas. These results suggest that expression of p21ras is a normal feature of more fully differentiated tissues, both normal and neoplastic, and is not useful as an indicator of cell proliferation or 'malignant potential'. PMID- 2189382 TI - Monitoring behavioural stress control using a craniomandibular index. AB - This study was concerned with the practical value of relaxation training in helping an individual reduce anxiety and its physical manifestations. Twenty-five subjects learned and practised transcendental meditation for a period of three months. Subjects were clinically examined before and after meditation training, and a craniomandibular index (CMI) was used to objectively assess criteria pertaining to mandibular function. Baseline and outcome CMI scores were compared for the group and shown to be significantly different. Deep relaxation achieved through transcendental meditation alleviated intramuscular tension and fatigue, promoting balanced, co-ordinated muscle function. PMID- 2189383 TI - Aptitude testing and the selection of dental students. AB - This paper discusses the problems involved in the selection of dental students and the need for some form of aptitude testing. It describes the situation in the United Kingdom both in the past and the present, and then describes in detail the situation in North America (both in the United States and Canada). The Dental Admission Test, its history and the research into its development are described with particular emphasis on the dexterity, perceptual and aptitude components of the test. More recent research into dexterity and aptitude testing of dental students is also covered. However, it is apparent that many questions remain unanswered. PMID- 2189384 TI - Glass ionomer cements. PMID- 2189385 TI - Treatment of epistaxis. AB - Episodes of epistaxes are annoying and sometimes life-threatening conditions that commonly present to general practitioners. Mostly they can be effectively managed in the surgery. PMID- 2189386 TI - Gordon Bell memorial lecture. Management of soft tissue sarcoma. PMID- 2189387 TI - Impact of fine needle aspiration cytology on the management of solitary thyroid nodules. AB - To evaluate the impact of the routine use of fine needle aspiration cytology (FNAC) on the management of solitary thyroid nodules, 102 consecutive patients were assessed in regard to the proportion of patients being subjected to surgery and the corresponding yield of malignancy. This cohort was compared with a historical control where FNAC was not routinely applied as a diagnostic selection criterion. The percentage of patients operated on had decreased from 95% to 60% (P less than 0.001) without any significant decrease in the field of malignancy: 18.6% vs 17.6% (P = 0.97). The yield of malignancy of patients operated on had increased from 18.4% to 26.2%. Of those not subjected to surgery, 14 patients or 14% of the original cohort experienced spontaneous complete resolution of their nodules after a mean follow-up period of 5.5 months (s.d. = 3.5) (non-resected group). In the retrospective evaluation of diagnostic discriminants to maximize yield of malignancy while minimizing unnecessary surgery for thyroid nodules, the use of combined parameters of clinical suspicion, positive FNAC and age greater than or equal to 50 years detected 100% of malignancies with only 50% of patients requiring surgery. This was superior to other modalities including clinical parameters and expensive investigations of radionuclide scans and ultrasonography. In conclusion, the use of FNAC in the evaluation of solitary thyroid nodules has resulted in a decreased proportion of patients requiring surgery and cost saving while maintaining the yield of malignancy. PMID- 2189388 TI - Sequential laparotomy and zipper closure in the management of gross peripancreatic sepsis. AB - Four cases of gross peripancreatic sepsis have been managed with repeated laparotomies and packing of the lesser sac. A zipper was used for abdominal closure in three patients and the abdomen was left open in one. Sequential laparotomy enabled repeated debridement of non-viable pancreatic and peripancreatic tissue and prevented intra-abdominal septic accumulations. An additional benefit of this technique was the frequent detection and correction of clinically unsuspected complications of the septic abdomen. PMID- 2189389 TI - Barbers and porters: commencement of academic anaesthesia in Australia. PMID- 2189390 TI - Unusual variant of right paraduodenal hernia. AB - An unusual case of internal hernia was encountered. Its clinical features, radiological investigation and anatomical findings at operation were discussed in relation to right paraduodenal hernia. Embryological consideration supported the view that this was, in fact, a variant of right paraduodenal hernia. No identical case has been reported in the literature. PMID- 2189391 TI - Symphysiotomy for the trapped aftercoming parts of the breech: a review of the literature and a plea for its use. AB - The most dreaded complication of vaginal breech delivery is entrapment of the aftercoming head. When this is due to disproportion, persistent attempts at vaginal extraction are likely to result in a dead or damaged baby. A largely unknown solution in this desperate predicament is to surgically enlarge the pelvis by means of a symphysiotomy. A review of the literature shows that symphysiotomy performed to free the trapped aftercoming head will save at least 80% of babies if the procedure is performed without delay. Every obstetrician should be prepared to perform a symphysiotomy if the aftercoming head is trapped. PMID- 2189392 TI - The influence of maternal height, obstetrical conjugate and fetal birth-weight in the management of patients with breech presentation. AB - The value of erect lateral X-ray pelvimetry for selecting patients for a safe trial of vaginal delivery was assessed in a retrospective study of 424 women with a breech presentation. A trial labour was more often allowed in women with larger inlet conjugate measurements and the chance of successful vaginal delivery was better with larger pelvic measurements. However, there was no absolute level of pelvic contraction below which vaginal delivery was impossible. The size of the fetus did not determine the rate of planned elective Caesarean section. A fetus weighing greater than 3,500 g, had less than 50% chance of vaginal delivery. It is suggested that antenatal assessment of fetal size should be considered in patients with breech presentation before deciding on the mode of delivery. PMID- 2189393 TI - Domiciliary fetal monitoring in a district maternity unit. AB - Domiciliary Fetal Monitoring is a new technique which allows fetal heart rate monitoring from within a patient's home. The 30 minute cardiotocograph is transmitted by telephone, to a central labour ward computer, within 45 seconds. Of 522 domiciliary cardiotocographs performed on 100 consecutive patients, 356 (68%) were performed for suspected intrauterine growth retardation or reduced fetal movements. Thirty one (5.9%) recordings were abnormal; a repeat cardiotocograph in hospital was abnormal in 9 cases (1.3%); all such patients were delivered within 7 days. The induction rate for the study group was increased by a factor of 3.2 with respect to all hospital confinements; 49% of infants were small for gestational age (less than 10th percentile). Caesarean section and forceps delivery rates were the same for both groups. No stillbirths occurred in the study group. After the introduction of domiciliary monitoring, the number and duration of hospital admissions for fetal surveillance were reduced by 29% and 52% respectively. Patients were equally as able as midwives to perform domiciliary fetal monitoring. A patient survey revealed widespread satisfaction with the DFM system. PMID- 2189394 TI - Chorion villus sampling--transcervical or transabdominal? AB - Chorion villus sampling was performed transcervically on 84 patients and transabdominally on 126 patients. Two of 4 (5%) spontaneous abortions in the transcervical group were complicated by uterine infection. Five (4%) spontaneous abortions in the transabdominal group were uncomplicated by infection. The results support the contention that the transabdominal method may be safer and that the procedure related fetal loss rate is similar to that following amniocentesis. PMID- 2189395 TI - The antiprogesterone steroid, RU 486 (mifepristone). AB - RU 486 (Mifepristone) represents a major development in the field of hormone antagonists as the first effective antiprogestogen. A number of therapeutic roles for the drug are envisaged. It is already being used extensively around the world for the procurement of first trimester abortion--particularly in combination with prostaglandins. It also has been shown to be effective as a cervical ripening agent and for the induction of labour. Initial human studies have involved nonviable pregnancies and more work is needed in animal models before the drug can be deemed safe for use in viable human pregnancies in the third trimester. PMID- 2189396 TI - Inferior vena cava ligation for intractable pelvic haemorrhage. AB - Inferior vena cava ligation was performed as the last resort in a case of iatrogenic injury to the common iliac veins during pelvic surgery. The post operative recovery was satisfactory. PMID- 2189398 TI - Sex determination and the Y chromosome: the application of molecular genetic technique to behavioral genetics. AB - In mammals, the Y chromosome mediates both gonadogenesis and spermatogenesis. It is also known to influence such traits as histocompatibility, sperm head morphology, pubertal (but not adult) testosterone level, sexual behavior, and aggressive behavior. An immediate goal in my laboratory is the isolation and characterization of the Y chromosomal gene responsible for initiating differentiation of the primitive bipotential gonads to become testes: the Y chromosomal gonadogenesis gene. Function of this gene initiates a cascade of events involving large numbers of other genes scattered throughout the genome, but it is not responsible for initiating development of all of the male phenotype; where : is XXSxr karyotype males, bearing the Sxr region of the Y chromosome which includes this gene, are sterile. It is not known if this gene influences those behaviors known to be influenced by the Y chromosome. If animals with an XXSxr karyotype, transgenic for specific Y chromosomal genes, could be produced, questions such as this could be answered. The developmental biology of the testis, molecular genetics of the Sxr region of the Y chromosome, and isolation of the testis determination gene from DNA of XXSxr males are discussed. Also discussed are the production of transgenic mice and the prospects for using such animals as coisogenic strains, differing by precisely known DNA sequences, in behavior genetic analysis. Such animals could be used both to test for behavioral phenotype and to dissect out biochemical and neurological mechanisms responsible for the behavior. PMID- 2189397 TI - The evolution of the mammalian Y chromosome. AB - There is a predominant theory for the evolution of the mammalian Y chromosome. This theory hypothesizes that genes for sex determination and male-specific traits, as well as sequences for X-Y meiotic pairing, are conserved on the mammalian Y chromosome across all lineages and that all other Y chromosomal genes or sequences have been or will be lost in each mammalian lineage. There are effects of mouse Y chromosomal genes on behaviors and other traits that are not male specific. Under the predominant theory, these Y chromosomal genes could be the same as the conserved genes for sex determination or male-specific traits, or they could be genes that have been lost from the Y chromosomes of other mammalian lineages and that will eventually be lost from the Y chromosome of the rodent lineage. Recently, the evolution of the primate and rodent Y chromosomes has been studied at the DNA level. These studies are summarized and reviewed in this article. The findings of these studies are not fully consistent with the predominant theory for the evolution of the mammalian Y chromosome. Also, they imply that there are other possibilities for the phylogenetic history of Y chromosomal genes of mice with effects on behavior. These are that Y chromosomal genes with effects on mouse behaviors or other traits could be conserved genes other than those for sex determination or male-specific traits or that they could be novel genes on the Y chromosome of the rodent or Mus lineage. PMID- 2189399 TI - Y chromosome and aggression in strains of laboratory mice. AB - Intermale attack behavior differences in laboratory strains of inbred mice have Y chromosome correlates in a small number of strain comparisons. Moreover, the Y correlates interact with autosomal or pseudoautosomal genes. Recent data on the genetics of the Y do not contradict these conclusions. The discovery of several polymorphic loci of the Y could pave the way for a direct confirmation of Y correlates of attack behavior by linkage detection. The involvement of the Y in this behavior has been put forward. Plasmatic testosterone concentration reactivity of some target organs to exogeneous testosterone appears to be correlated with two independent loci of the Y acting in an additive or interactive manner with autosomal or pseudoautosomal loci. However, the association between testosterone action and attack behavior in males needs further evidence, and in any case this association does not underline linear mechanisms. PMID- 2189400 TI - The phorbol ester TPA induces a translocation of the insulin sensitive glucose carrier (GLUT4) in fat cells. AB - Insulin activates the glucose transport in isolated fat cells through a translocation of the insulin sensitive glucose carrier subtype (GLUT4) and by activation of glucose carriers in the plasma membrane. Protein kinase C stimulating phorbol esters are able to mimick partially the insulin effect on glucose transport. In order to determine whether this phorbol ester effect occurs through a translocation of the insulin sensitive glucose carrier (GLUT4) we used a monoclonal antibody against GLUT4 to determine its distribution in subcellular fractions of rat adipocytes. We found that the phorbol ester TPA is able to increase the amount of GLUT4 in the plasma membrane fraction about two-fold. PMID- 2189401 TI - Evidence for nonintercalative complexes formed from the reversible binding of benzo[a]pyrene metabolites to closed-circular, single-stranded M13mp19 DNA. AB - The fluorescence excitation spectrum of complexes formed from the reversible binding of the proximate carcinogen, trans-7,8-dihydroxy-7,8-dihydro benzo[a]pyrene (BP78D) to closed-circular, single-stranded, viral M13mp19 DNA (SS M13 DNA) exhibits a red-shift of 5 nm compared to the spectrum of BP78D measured without DNA or with native, calf thymus DNA. In SS M13 DNA which is 0.10 mM in PO4-, the fluorescence intensity of BP78D is 2.3 times smaller than the intensity measured without DNA; however, the fluorescence lifetime (42.7 nsec) of BP78D with SS M13 DNA is 1.7-1.8 times larger than the lifetimes of BP78D measured without DNA or with calf thymus DNA. These results are consistent with the conclusion that, in addition to binding sites which cause fluorescence quenching, SS M13 DNA contains sites which permit formation of BP78D inclusion complexes that have weaker interactions with nucleotide bases than those occurring in intercalated complexes. The association constant (1.45 +/- 0.01 x 10(5) M-1) for the binding of BP78D to SS M13 DNA is more than 9.0 times larger than that for binding to calf thymus DNA. It is 7.1 times larger than that for the binding of the less genotoxic metabolite, trans-4,5-dihydroxy-4,5-dihydrobenzo[a]pyrene (BP45D) to SS M13 DNA. UV Photoelectron data and results from ab initio molecular orbital calculations suggest that a difference in polarizability contributes to the greater SS M13 DNA binding of BP78D compared to that of BP45D. PMID- 2189403 TI - Effect of erythroid differentiation factor on erythroid differentiation and proliferation of K-562 cells. AB - The effects of erythroid differentiation factor (EDF) on the levels of zeta globin and several proto-oncogene mRNAs and transferrin receptors (Tf-R) of K-562 cells were examined. EDF decreased Tf-R expression and increased the level of zeta-globin mRNA. The mRNA level of c-fos began to rise within 3 hours and continued to increase up to 72 hours, but the levels of c-myb and c-abl decreased to 23 and 19%, respectively, of their initial levels after 48 hours. In contrast, the mRNA levels of c-myc and c-fms decreased transiently, but recovered within 48 hours. The modulation of several proto-oncogene mRNA levels was observed much earlier than the differentiation induction and the growth inhibition of K-562 cells by EDF. PMID- 2189402 TI - Identification and characterization of endothelin converting activity in cultured bovine endothelial cells. AB - Using a specific and sensitive radioimmunoassay (RIA) for the carboxyl terminal tail of endothelin (ET) (His16-Trp21), we have confirmed the presence of the converting activity from synthetic human big ET-1 to ET-1 in the homogenate of cultured bovine aortic endothelial cells. The optimal pHs for the converting activities were found at pH 3.0 and pH 7.0. The activity at pH 3.0 was completely inhibited by pepstatin A, whereas the activity at pH 7.0 was not affected by known various protease inhibitors except EDTA and EGTA. When the products from big ET-1 were analyzed on an ODS and a CN columns, only ET-1 was detected at pH 7.0, but various ET-like immunoreactivities other than ET-1 were detected at pH 3.0. These findings strongly suggest that mature ET-1 is formed from big ET-1 in the endothelial cells by a metal-dependent neutral protease. PMID- 2189404 TI - Purification and complete amino acid sequence of novel beta 2-microglobulin. AB - We have previously reported that novel beta 2-microglobulin (beta 2m) is a metabolite derived from beta 2m in ultrafiltrate of patients on long-term hemodialysis (LT-HD). Chromatofocusing showed the presence of at least two major novel beta 2m's with isoelectric points of 5.38 and 5.22. In the present study we purified one of major novel beta 2m's and determined the complete amino acid sequence. We demonstrate herein that the novel beta 2m has the same sequence as native beta 2m except for the 17th residue from the N-terminus which was identified as Asp instead of Asn in native beta 2m, suggesting a possible deamidation during LT-HD. PMID- 2189405 TI - Purification and characterization of putative endothelin converting enzyme in bovine adrenal medulla: evidence for a cathepsin D-like enzyme. AB - A specific and sensitive assay has been established for measurement of endothelin converting activity in a tissue extract. This assay is based on measuring endothelin-1 generated from big endothelin-1 by endothelin converting enzyme (ECE) with radioimmunoassay using an endothelin C-terminal specific antibody. By using this assay, we purified and characterized ECE in bovine adrenomedullary chromaffin granules ECE was purified over 3,000 times by a combination of DEAE, hydrophobic and gel filtration chromatography. A molecular weight of ECE was estimated to be approximately 30,000 by gel filtration. Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed that ECE had three major components with estimated molecular weights of 45,000, 30,000 and 15,000 like bovine spleen cathepsin D. ECE had a pH optimum at 3.5 and was inhibited by pepstatin. These results strongly suggest that ECE is a cathepsin D-like aspartic protease. PMID- 2189406 TI - A macrophage LPS-inducible early gene encodes the murine homologue of IP-10. AB - Recently, we have isolated and characterized a set of cDNA clones which encode lipopolysaccharide-inducible proteins in murine peritoneal macrophages. Here, we report the sequence and identification of one of these cDNAs previously termed C7. Nucleotide sequence analysis revealed an open reading frame encoding a predicted polypeptide composed of 98 amino acids, which contained a 21 amino acid residue signal peptide, indicating approximately 9 kDa of mature protein. The deduced protein sequence showed homology (67% identity, 77% considering conservative amino acid changes) with the human INF gamma-inducible gene IP-10, a member of the recently described superfamily of chemotactic and mitogenic proteins which includes platelet factor 4, monocyte-derived neutrophil chemotactic factor (NAF, NAP-1, IL-8), and MGSA/gro/KC. Thus C7 would appear to represent the murine homologue of the human IP-10 gene or a very closely related gene. PMID- 2189407 TI - Complementation of the Aspergillus nidulans arg B1 mutation by ornithine transcarbamylase cDNA from rat liver. AB - An Aspergillus nidulans strain which is deficient in ornithine transcarbamylase due to the arg B1 mutation was transformed with a plasmid containing the ornithine transcarbamylase cDNA from rat liver under the control of the amd S promoter. Stable transformants were obtained by selection on arginine free medium indicating complementation of the arg B mutation. Proof of expression of the rat enzyme in transformants was obtained by immunoprecipitation of all ornithine transcarbamylase activity from cell extracts with antibodies specific for the rat enzyme. The presence of catalytically active rat ornithine transcarbamylase in the transformants indicated that it is capable of being imported into mitochondria in A. nidulans, proteolytically processed and assembled into its homotrimeric form. In vitro uptake experiments using isolated A. nidulans mitochondria demonstrate that processing of the precursor of rat ornithine transcarbamylase occurs in two temporally separated steps as it does in rat liver mitochondria suggesting evolutionary conservation of the processing machinery. Up to 560 ng of active rat enzyme was produced per gm wet weight mycelia. Use of beta-D-alanine, an inducer of amd S, as sole N-source resulted in increased levels of active rat ornithine transcarbamylase relative to uninduced cultures. PMID- 2189409 TI - Complete amino acid sequence of yeast thioltransferase (glutaredoxin). AB - The amino acid sequence of a thioltransferase isolated from Saccharomyces cerevisiae was determined. The protein was cleaved by trypsin, Staphylococcus aureus V8 protease, and cyanogen bromide. The peptides generated were purified by reverse phase HPLC. Sequencing of intact protein and its fragments were achieved by automated Edman degradation. The protein contains 106 amino acid residues with two cysteines. Yeast thioltransferase showed 51% structural similarity to pig liver thioltransferase and 34% to E. coli glutaredoxin. PMID- 2189408 TI - High-level expression in Escherichia coli of the catalytically active flavin domain of corn leaf NADH:nitrate reductase and its comparison to human NADH:cytochrome B5 reductase. AB - Higher plant nitrate reductase can be divided into three functional domains representing its prosthetic groups: 1) flavin; 2) cytochrome b; and 3) Mo-pterin. The flavin domain has been synthesized by heterologous expression in Escherichia coli using a fragment of a corn leaf NADH:nitrate reductase cDNA clone, Zmnr1, which we had previously isolated and sequenced. A Xho2-BamH1 fragment was cut from Zmnr1, containing the sequence for the flavin domain, and ligated in the BamH1 site of expression vector pET3c. When this construct was expressed in E. coli, a 30 kD polypeptide was found to be newly synthesized. The flavin domain was purified to homogeneity using blue Sepharose and shown to have a molecular weight of 30 kD. The recombinant flavin domain has a ferricyanide reductase specific activity of 1000 mumols NADH oxidized/min/mg protein and a visible spectrum virtually identical to that of human NADH:cytochrome b5 reductase. PMID- 2189410 TI - Phi 80 transcription antitermination complex: a 15 kDa host-coded protein interacts with the gene N transcription antitermination protein of bacteriophage phi 80. AB - We purified the transcription antitermination complex of phi 80 (phi 80-pN complex). This complex had a molecular weight of approx. 42,000, and the subunits of this complex could be separated by SDS polyacrylamide gel electrophoresis. The complex was composed of two different polypeptides, one was the phi 80 N gene product (phi 80-pN) with a molecular weight of approx. 12,000, and the other was a host-coded protein with a molecular weight of approx. 15,000. The densitometric analysis after SDS polyacrylamide gel electrophoresis showed that the molar ratio of two proteins was 2 to 1 (phi 80-pN: 15 kDa), and the complex was assumed to be a trimer. Bacteriophage phi 80 could grow in nusA, nusC, and nusE mutants of Escherichia coli, but failed to grow in a nusB mutant. The molecular weight of the nusB gene product is calculated to be 15,689 from the sequencing data. These results suggest that the partner of the N gene product is possibly a host-coded nusB gene product. PMID- 2189411 TI - Tightly controlled expression systems for the production and purification of Escherichia coli release factor 1. AB - The genes for the protein release factors in Escherichia coli have traditionally proven difficult to maintain on high copy plasmids. We have established here systems which provide for both stable maintenance of the release factor 1 gene on such plasmids, as well as high level overproduction of the release factor 1 protein. The gene is maintained under the control of the inducible trc or tac promoters in the presence of very high levels of lac repressor. A simple and rapid scheme for the purification of RF1 from extracts of cultures carrying these plasmids is also described. PMID- 2189412 TI - A procedure for cloning restriction fragments of DNA as single inserts in yeast artificial chromosomes. AB - A novel procedure is described for the cloning of partial EcoRI fragments of bovine DNA: it reduces the chance of sequence rearrangements due to multiple insertions (co-cloning) of restriction fragments in the resulting YAC. The DNA to be inserted has been dephosphorylated, whereas the matching ends of the vector, pYAC4, have not. The ligation was essentially complete, the transformation efficiency was close to 19 transformants per ng of vector and the frequency of clones carrying YAC, 60-100 kb in size, was close to 70%. The YACs show segregative and replicative stability. PMID- 2189413 TI - Acceptance speech on the occasion of receiving the d'Arsonval medal. PMID- 2189414 TI - Extremely low-frequency electric and magnetic fields and risk of human cancer. Ad Hoc Working Group. AB - The reported association between the risk of human cancer and exposure to 50- or 60-Hz electric and magnetic fields is difficult to evaluate from studies published to date. The association is now being reexamined in several large epidemiologic studies. In most of the studies, exposure will be assessed with newly designed, portable meters that allow direct and precise measurements of exposure to be performed easily for large numbers of individuals. The main features of the studies are summarized. At a meeting of principal investigators held in 1988 at the International Agency for Research on Cancer, broad guidelines were agreed for the design of this new generation of studies. These guidelines should improve the comparability of results and eventually provide a clearer assessment of human-cancer risk from exposure to extremely low-frequency electric and magnetic fields. PMID- 2189415 TI - [Conformation analysis of carbohydrate chains of glycoconjugates]. AB - A problem of conformations of carbohydrate chains of glycoconjugates glycoproteins and glycolipids--is reviewed. Experimental data (NMR, X-Ray) and theoretical conformational analysis data are discussed. Spatial structures of O linked oligosaccharides from blood-group glycoproteins, N-linked oligosaccharides of different types (oligomannosidic, complex, hybrid, bisect) and carbohydrate chains of glycosphingolipids are considered. PMID- 2189416 TI - Biochemical demonstration of calpains and calpastatin in osteoarthritic synovial fluid. AB - Calpains (calcium-dependent cysteine proteinases; optimum pH 7.0-7.5) have been regarded as intracellular proteinases. We examined the cell-free components of synovial fluid from 14 patients with osteoarthritis and demonstrated the existence of calpains, as the caseinolytic activities of chromatographic fractions, together with calpastatin, the specific endogenous inhibitor of calpains. The presence of these calpains and calpastatin was verified by immunoblotting with their respective specific antibodies. Calpain fractions showed proteoglycan-degrading activity. The results suggest that the calpain calpastatin system may contribute to the turnover of cartilage matrix components. PMID- 2189417 TI - A randomized controlled trial of ciamexon versus placebo in the immunomodulatory treatment of rheumatoid arthritis. AB - To determine the efficacy of the new immunosuppressive agent ciamexon in patients with rheumatoid arthritis (RA), we conducted a 6-month, prospective, double blind, placebo-controlled study. The study included 21 outpatients with confirmed RA, who were randomized into 3 treatment groups of 7 patients each. Group 1 received 400 mg/day of ciamexon, group 2 received 100 mg/day of ciamexon, and group 3 received placebo. We investigated the influence of ciamexon on the clinical course, the systemic inflammatory activity, and the lymphocyte subsets in the peripheral blood. Significant, dose-dependent improvement was seen in both the clinical and the biochemical activity indexes at the end of the treatment period (P = 0.02 to P = 0.05). The proportion of activated T lymphocytes was significantly decreased (P = 0.05), and the proportion of CD8-positive lymphocytes was significantly increased (P = 0.03) in patients taking ciamexon. The major adverse effects were hepatotoxicity (2 patients) and rash (2 patients). This study documents the clinical efficacy of ciamexon therapy in RA patients and identifies the agent's potential toxicity. PMID- 2189418 TI - The influence of serum dilution on findings of antiperinuclear factor prevalence in rheumatoid arthritis. PMID- 2189419 TI - Effects of pioglitazone on glucose and lipid metabolism in Wistar fatty rats. AB - Insulin resistance is one of pathogenic factors for non-insulin-dependent diabetes mellitus (NIDDM). Pioglitazone (5-[4-[2-(5-ethyl-2-pyridyl) ethoxy]benzyl]-2,4-thiazolidinedione, AD-4833, also known as U-72, 107E) is a promising candidate to lower hyperglycemia by reducing insulin resistance. The genetically obese-hyperglycemic rats. Wistar fatty, were used to test the action of pioglitazone, because they develop severe insulin resistance in the peripheral tissues (muscle and adipose tissue) and liver. Pioglitazone administered orally (0.3-3 mg/kg/d for 7 days) dose dependently reduced hyperglycemia, hyperlipidemia, and hyperinsulinemia in male fatty rats. Pioglitazone improved glucose tolerance and augmented the glycemic response to exogenous insulin and clearance of plasma triglyceride. These effects on glucose and lipid metabolism seem to be due to increased insulin sensitivity and responsiveness in the peripheral tissues, because pioglitazone increased insulin-stimulated glycogen synthesis and glycolysis in the isolated soleus muscles, and insulin-stimulated glucose oxidation and lipogenesis in adipocytes. The latter effects were not accompanied by any changes in insulin binding. The actions of insulin mimickers (vanadate and vitamin K5), which act on the post-insulin binding sites, on these metabolic events were also potentiated by pioglitazone. These findings suggest that pioglitazone can improve glucose and lipid metabolism by reducing insulin resistance on the post-binding system. Therefore, pioglitazone may be efficacious for treating human NIDDM. PMID- 2189420 TI - Effect of a new xanthine derivative on the release of insulin from rat pancreatic islets. AB - S 9795 (1-methyl-3-isobutyl-8-[2-ethyl 1-(4-diphenylmethylpiperazinyl)]- 3,7 dihydro(1H)purine-2,6-dione) is a new xanthine derivative displaying antiasthmatic properties in animals. The drug might exert its pharmacological actions either by inhibiting phosphodiesterases, or by inhibiting cellular Ca2+ movements or antagonizing purinoreceptors. Since the process of glucose-induced insulin release is markedly influenced by xanthine derivatives, the effect of S 9795 was compared to that of two other xanthine derivatives (theophylline and 3 isobutyl-1-methylxanthine (IBMX] on glucose-induced insulin release and ionic fluxes in rat pancreatic islets. Theophylline and IBMX potentiated glucose induced insulin release, as expected, while S 9795 inhibited the insulinotropic effect of glucose. The effect of S 9795 was observed at a concentration of 10(-5) mol/l, lower concentrations (10(-6) to 10(-9) mol/l) failing to affect glucose induced insulin release. At 10(-5) mol/l, the drug also inhibited the secondary rise in 45Ca efflux evoked by glucose from preloaded islets and the uptake of 45Ca by incubated islets stimulated either by glucose or potassium. The drug failed to alter 86Rb fluxes in stimulated and unstimulated islets labelled with the radioisotope. These data show that S 9795 inhibits glucose-induced insulin release, possibly by blocking glucose-stimulated Ca2+ inflow into the B-cell. PMID- 2189421 TI - [Transgenic mice as disease models]. AB - The methods used for making transgenic mice such as DNA microinjection in pronuclei, transformation of embryonic stem cells and production of chimeras, infection by retroviral vectors and sperm cells as carriers for foreign DNA are reported. Furthermore some characteristics of transgenic mice are mentioned, in particular factors influencing integration and expression of gene constructs. Different kinds of disease models using transgenic mice are available. This has been achieved by insertional mutagenesis, dominant negative mutations, changes caused by overexpression of transgenes, gene ablation, targeted mutation, and transfer of oncogenes. The importance of ongoing research in transgenic animals is emphasized. PMID- 2189422 TI - [An isolated intestinal form of infantile myofibromatosis]. AB - Infantile myofibromatosis is the most common form of fibromatosis in children. It can be solitary, mainly affecting the bone or soft tissues, or multicentric with the possibility of visceral involvement. Solitary forms of visceral localization are exceedingly rare. The authors report the observation of a newborn female infant, with solitary jejunal infantile myofibromatosis which after reviewing relevant litterature on the subject appears to be the sixth case of its kind. This form must be considered in the differential diagnosis of the neonatal intestinal obstruction. PMID- 2189423 TI - [Macroscopic study of surgical breast specimens. A modern approach]. AB - The different types of surgical breast specimens encountered by the pathologist are described. The macroscopic examination and blocking procedure are reviewed, including some recommendations based on the personal experience of the two authors. PMID- 2189424 TI - [Computer-assisted processing of screened cervico-vaginal smear reports. The A.D.I.C.A.P. Bull-Sopra system]. PMID- 2189425 TI - [Dysplastic nevus]. PMID- 2189426 TI - [The association of neuro-endocrine carcinoma of the skin and Bowen's disease. Review of the literature apropos of 4 cases]. AB - Four cases of neuroendocrine carcinoma following Bowen's disease are presented. An immunohistochemical study was performed. The four patients, 3 men and a woman, ranging from seventy to eighty-seven years of age, developed a nodular tumor on a preexisting cutaneous lesion. In one of those cases the diagnosis of Bowen's disease was confirmed histologically before the apparition of the nodular tumor. The tumors were localized on the scalp, thorax, dorsum of the hand, and the scrotum. The four tumors were immunohistologically typical of neuro-endocrine carcinoma: there was a positivity for neurofilaments, cytokeratins and neurone specific enolase. The clinico-pathological characteristics of those 4 neuro endocrine carcinomas associated with a Bowen's disease, when compared with the 15 similar described in the literature, are identical to the isolated neuroendocrine carcinoma, from a clinical, morphological and evolutional point of view. The majority are seen in patients older than 60 years old and one third of the cases described survived at least 5 years. The coexistence of Bowen's disease and neuroendocrine carcinoma, the association of neuroendocrine and epidermoid cells in other cutaneous tumors, reactivate the controversy concerning the histogenesis of the so-called Merkel cell carcinoma. In fact, the histogenesis of the tumor is still not fully understood. PMID- 2189428 TI - A randomized controlled trial of a nursery ritual: wearing cover gowns to care for healthy newborns. AB - The routine wearing of individual cover gowns by nurses and visitors for direct care of healthy newborns was usual practice on the maternity ward of a regional referral center. We conducted a randomized trial in which cover gowns were not provided for care of infants in the experimental group (n = 222), but were maintained for control infants (n = 230). The principal outcome measured was Staphylococcus aureus colonization of the newborn nares or umbilicus on day 3 or day of discharge. Twenty percent (n = 51) of the experimental group (no gown) had a positive culture compared with 21 percent (n = 47) of the controls. Of the infants with positive cultures, two in each group exhibited symptoms of overt S. aureus infection. Experimental infants were similar to controls with respect to feeding method, route of delivery, amount of time spent rooming-in, and average number of visitors per day. In the group of positively cultured infants, the mothers experienced longer labor, and more vaginal examinations in labor, and the number of males undergoing circumcision was higher. We concluded that routine use of cover gowns was unwarranted, and we have altered the ward policy accordingly. This also has had a positive economic effect. PMID- 2189427 TI - [Mycotic infection in immunosuppressed patients. An anatomopathologic study]. AB - Mycotic infections are a frequent and often severe complication in the immunosuppressed patient. A review of autopsy findings in 54 cases with gross, histologic and mycologic studies was undertaken among immunocompromised patients after chemotherapy or allogenic bone marrow transplantation: fungal infections were either localized especially in lungs and gastrointestinal tract, or disseminated. Fungi were various: principally Candida and Aspergillus, but also Fusarium, Torulopsis and Trichosporon. In acquired immunodeficiency syndrome (11 autopsy cases), mycotic infections appeared different. Oral and esophageal candidiasis could be found, but cryptococcosis and histoplasmosis were the major generalized mycosis. This study suggests that fungal infections are not the same in patients treated by chemotherapy or bone marrow transplantation, and in acquired immunodeficiency syndrome. PMID- 2189429 TI - Oral physostigmine as treatment for primary degenerative dementia: a double-blind placebo-controlled inpatient trial. AB - Twenty-three patients with primary degenerative dementia (Alzheimer's disease) were administered an optimal dose of oral physostigmine and placebo, each for a 1 week period, under double-blind conditions on a research unit of a general hospital. Each patient served as his or her own control. The optimal dose of physostigmine for each patient was determined previously by a dose-finding phase. There were no significant group differences on a number of neuropsychological tests. Along with other studies in the literature, this study casts serious doubt on the efficacy of short-term administration of oral physostigmine when used alone in an attempt to ameliorate cognitive dysfunction in Alzheimer's disease patients. The possibilities that physostigmine may slow the course of the disease or may acutely improve symptoms when combined with other agents are discussed. PMID- 2189430 TI - Hydergine treatment and psychophysiological measures in primary degenerative dementia. AB - Changes in smooth pursuit eye movements and the P300 component of the auditory evoked potential were studied in patients with primary degenerative dementia during a double-blind, placebo-controlled study of ergoloid mesylates (Hydergine). After 18 weeks of treatment, P300 latency and amplitude, recorded at three scalp electrode sites, had not changed significantly. Smooth pursuit gain was elevated for the drug group under some stimulus conditions, suggesting a normalization of pursuit eye movement functioning. However, the results of several other measures of the quality of pursuit eye movements failed to corroborate this finding. PMID- 2189431 TI - Novel phenotype of C3H 10T1/2 fibroblasts cotransfected with the c-Ha-ras and adenovirus 5 E1A oncogenes. AB - C3H 10T1/2 fibroblasts are converted to fully transformed phenotype following coexpression of an activated c-Ha-ras gene and either a constitutively expressed viral or cellular myc gene. In this report, we examined whether the early region 1A (E1A) of adenovirus 5, which synergizes with ras to convert primary embryonic cells to a transformed phenotype, can synergize with ras to transform the established mouse embryonic cell line, C3H 10T1/2. We demonstrate that coexpression of ras and E1A generated a transformed phenotype that could be scored by colony assays and by soft agarose assays but not by standard focus assays. The ras-E1A-transformed phenotype relies on sequences present in conserved regions 1 and 2 of the E1A proteins and, in part, on information encoded by the extreme carboxy terminus of E1A. The contrast between the transformed phenotypes generated following the transfection of C3H 10T1/2 cells with either ras and myc or ras and E1A suggests that myc and E1A cooperate with ras to transform C3H 10T1/2 cells by mechanisms that can be distinguished using this established cell line as a model system. PMID- 2189432 TI - Cell surface antigen expression of first trimester chorionic villus samples. AB - First trimester chorionic villi obtained by chorionic villus sampling at approximately 9 weeks of gestation were investigated by indirect immunofluorescence to demonstrate trophoblast cell surface antigen expression. Villous trophoblast expressing the trophoblast specific markers transferrin receptor, human placental lactogen, and cytokeratin was also found to express a monomorphic major histocompatibility complex class I determinant recognized by the monoclonal antibody W6/32. W6/32 positive regions included sparsely scattered regions of villous trophoblast and fanning outgrowths of trophoblast. The class I antigenic determinant expressed by first trimester trophoblast was found to be recognized exclusively by W6/32 when assayed with a panel of anti-class I determinant monoclonal antibodies. Trophoblast W6/32 determinant expression was not increased after 24 hour organ culture in the presence of 200 U of interferon gamma. Exposure to interferon gamma resulted in increased class I antigen expression by mesenchyme and low level de novo mesenchyme class II antigen expression. These data suggest that early gestational stage villous trophoblast express non-classical class I antigens which do not seem to be subject to the regulatory effects of interferon gamma. PMID- 2189434 TI - Active immunization against LHRH: I. Effects of conjugation site and dose. AB - Active immunization against LHRH is a promising method of contraception for men. In order to be acceptable, sufficient amounts of anti-LHRH antibodies must be induced rapidly after vaccination. In previously reported animal studies, we found that it took considerable time (up to 5 months) to obtain antibody titers (AT) that were sufficiently high for complete suppression of spermatogenesis. The possibility of accelerating the immune response to LHRH by increasing the dose of immunogen was investigated in the male rat. Six doses of LHRH conjugated to tetanus toxoid (TT) in the 10 position (LHRH10-TT), ranging from 2.5 to 612 micrograms, and three doses of LHRH1-TT (50 to 612 micrograms) were tested. The magnitude of the immune response did not depend on the dose of the antigen, provided a threshold dose had been surpassed. Antigenicity of LHRH conjugated to TT at either the 1-, 6-, or 10-position was compared in rats and rabbits. In both species LHRH1-TT induced sufficient antibody concentrations to suppress pituitary gonadotropins (LH and FSH) and, subsequently, serum testosterone (T) levels faster than either the 6- or 10-conjugates. Only materials permitted for use in humans were utilized in these experiments. CONCLUSION: Active immunization against LHRH conjugated to TT at the 1-position has potential as a fast, convenient method of male contraception. PMID- 2189433 TI - Characterization of autoantigens relevant to experimental autoimmune orchitis (EAO) in mice immunized with a mixture of syngeneic testis homogenate and Klebsiella O3 lipopolysaccharide. AB - Experimental autoimmune orchitis (EAO) in mice has been induced by repeated injection of a mixture of syngeneic testis homogenate and Klebsiella O3 lipopolysaccharide (KO3 LPS) as a potent adjuvant. The antisera obtained from mice with EAO lesions defined several antigens with apparent molecular weights (MW) of 38,000 (38 kd), 86 kd, 100 kd, and greater than 200 kd by the immunoblotting method. These antigens were organ-specific and exclusively present on the acrosome of spermatozoa, suggesting that these acrosomal antigens were highly relevant to EAO. It was found that the antigen with a fairly high MW (greater than 200 kd) was expressed on spermatozoa from the epididymis. Furthermore, the acrosomal 86 kd antigen was predominantly expressed in the testis, while the 100 kd antigen was dominant in the spermatozoa from the epididymis. It was therefore suggested that the 86 kd and 100 kd antigens in the acrosome were differentially expressed on the process of maturation of spermatozoa. PMID- 2189435 TI - Extended breastfeeding as a legal issue: an annotated bibliography. PMID- 2189436 TI - Time was ... the care of the child in health. 1910. PMID- 2189437 TI - [Intestinal malacoplakia in childhood. Report of 5 cases]. AB - We studied 5 children with intestinal malakoplakia who were seen during a period of 10 years. Four were male and one female. The main clinical manifestations were: chronic bloody and mucous diarrhea, abdominal pain and polypoid masses detected by rectal maneuver. Either the radiological study as well as endoscopy showed the presence of stenosis and polypoid masses (pseudopolyps). Two patients underwent laparotomy and a tumoral infiltration at the level of rectal-sigmoid and cecal appendix was found. Histological diagnosis proves to be definitive in these case. Drug treatment has been with bethanechol, trimethoprim sulfamethoxazole in three patients. We conclude that intestinal malakoplakia is more common that ulcerative colitis in our children population attending at this institute. Therefore, the presence of intestinal malakoplakia must be ruled out in every child having chronic bloody and mucous diarrhea, presenting as well pseudopolyps. PMID- 2189438 TI - [Cystic lymphangioma of epiploon simulating ascites. Presentation of a case and review of the literature]. AB - We present a case of a 6 year old male who was admitted to the Hospital Infantil de Mexico Federico Gomez with a history of previous management in a secondary care facility, during a three year period, with the diagnosis of recurrent ascites. We established the diagnosis of an omentum cystic lymphangioma and revised the international literature, emphasizing on the different of clinical presentations, study protocol, differential diagnosis and therapy. PMID- 2189439 TI - [Bronchial hyperreactivity or broncho obstructive hyper response]. AB - In this article bronchial hyperreactivity (BHR) is defined and a series of factors which may be involved are discussed: genetic, neurovegetative imbalance, increase in the bronchial epithelial permeability, inflammation and mechanical factors which cause the shortening of the bronchial smooth muscle. A less rigid bronchial cartilage and a decrease in pulmonary elasticity, as well as a thickening of the bronchial wall due to a relative hypertrophy of the glandular tissue might just explain the occurrence of bronchial hyperreactivity in breast feeding newborns, which actively wheeze and later outgrow the abnormality, and those cases of persistent BHR who repeatedly wheeze. This hyperbronchial response reappears with the aging of the lung tissue. PMID- 2189440 TI - [Sodium concentrations in solutions for oral rehydration in children with diarrhea]. AB - Using the appropriate treatment for dehydration due to diarrhea, over a million deaths a year in children under five are being prevented. After analyzing the information related to the concentration of sodium in solutions used for oral rehydration, the following conclusions can be made: 1. Solutions with high glucose content, as well as hyperosmolar foods, favor the development of hypernatremia. Not so, sodium concentrations of up to 90 mmol/L, with glucose under 2.5%. 2. There are other factors which correlate with the presence of hypernatremia: abundant watery diarrhea, a good state of nutrition, under six months of age and the administration of solute loads, orally (boiled milk) as well as intravenously. 3. The WHO oral rehydration solution which contains, in mmol/L: sodium 90, glucose 111 (2%), chloride 80, potassium 20 and citrate 10, with a total osmolarity of 311 or 331 mOsm/L, is the one which more closely resembles the ideal concentration and has shown to be effective, not only in the treatment of dehydration due to diarrhea, but has also been to be useful in the prevention and maintenance of rehydration, independently from the etiology, the patient's age or the state of nutrition. 4. The use of oral serum with a sodium concentration of 90 mmol/L, reduces the natremia more slowly, therefore protecting the patient with hypernatremic dehydration from developing convulsions during treatment. This sodium concentration is also the best for cases of hyponatremic dehydration. 5. Using the recommended norms in cases of children with diarrhea, including continuing regular feeding habits and the adding of complementary liquids, no cases of hypernatremia have been recorded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189441 TI - Effects of chronic intrahypothalamic infusion of insulin on food intake and diurnal meal patterning in the rat. AB - In Experiment 1, rats were chronically infused with insulin (2.7, 27, or 270 ng/hr) or 0.9% saline into the ventromedial (VMH), medial perifornical (PF), or lateral (LH) hypothalamus. VMH infusions of insulin caused a significant, dose dependent decrease in food intake and body weight; PF infusion of insulin was less effective, but significant; whereas LH infusions of insulin were ineffective. In Experiment 2, rats were chronically infused with insulin (0.54 ng/hr) or 0.9% saline into the VMH, paraventricular (PVN), or posterior (PN) hypothalamic nucleus. Subjects that received VMH or PN infusions of insulin failed to regain weight lost as a result of surgery even 2 weeks after infusion; subjects that received PVN infusions of insulin regained their preoperative weights faster than did controls. All of the groups that received insulin significantly increased their daytime food intake during the infusion period and decreased their night food intake slightly; 24-hr food intake remained unchanged. PMID- 2189442 TI - Infusion of recombinant human prorenin into rhesus monkeys. Effects on hemodynamics, renin-angiotensin-aldosterone axis and plasma testosterone. AB - Prorenin, the biosynthetic precursor of active renin, is present in high concentrations in the kidney and reproductive organs. We have proposed that prorenin may be the vehicle of local renin systems, separating the functions of circulating and tissue renin. In the present study, we investigated the effect of increasing plasma prorenin 3- to 4-fold by infusing recombinant prorenin, 400 ng/min for 40 min, into male rhesus monkeys. The prorenin was first warmed to 37 degrees C to reduce the endogenous renin activity to a minimum. The study included a 20 min baseline and a 40 min recovery period. Plasma prorenin increased from 72 +/- 14 ng/mL/h to a maximum of 246 +/- 18 ng/mL/h during the infusion (P less than .001) and fell to 169 +/- 23 ng/mL/h 40 min after the infusion was stopped. Active renin did not change significantly. Plasma aldosterone increased slightly during the prorenin infusion (by 13%) and returned to baseline during the recovery period (P less than .05 compared to the infusion period). Plasma testosterone fell significantly from 1.9 +/- 0.1 ng/mL to 1.6 +/- 0.1 ng/mL during the infusion and further to 1.4 +/- 0.1 ng/mL during the post infusion period (P less than .05). Blood pressure fell slightly but not significantly. Heart rate, glomerular filtration rate and renal blood flow, as well as urine flow and urine sodium and potassium excretion showed no significant change. These results demonstrate that human recombinant prorenin is not converted to active renin in the circulation of rhesus monkeys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189443 TI - Endothelin does not affect intracellular calcium ion concentration in the platelets of rats. AB - We recently demonstrated that porcine endothelin increases intracellular calcium ion concentration ([Ca2+]i) in monolayers of cultured vascular smooth muscle cells isolated from rat renal arteries. The present study was designed to examine the effect of porcine endothelin on [Ca2+]i in the platelets of rats. [Ca2+]i was serially measured with the fluorescent dye, fura 2, and the photoprotein, aequorin. Endothelin (10(-9) mol/L, 10(-8) mol/L, and 10(-7) mol/L) did not induce any change in [Ca2+]i in the platelets of rats while thrombin (2 U/mL) dramatically increased [Ca2+]i as measured by these methods. Our results indicate that [Ca2+]i in rat platelets is not influenced by porcine endothelin. PMID- 2189444 TI - Imbalance of endothelium-derived relaxing and contracting factors. A new concept in hypertension? AB - The endothelium has a strategical anatomical position between the circulating blood and vascular smooth muscle cells. It has recently been recognized that endothelial cells play an important regulatory role in the circulation. The cells metabolize or activate vasoactive hormones (ie, norepinephrine, serotonin, bradykinin, angiotensin II), produce substances involved in coagulation and can release endothelium-derived relaxing factors and contracting factors. Nitric oxide and prostacyclin are vasodilators and inhibitors of platelet function. Endothelin is the most potent vasoconstrictor substance known. Thus, the endothelium can profoundly affect platelet adhesion and aggregation, vascular smooth muscle tone and possibly also vascular smooth muscle growth. Under physiological conditions, endothelium-derived relaxing factors appear to dominate. In contrast, in hypertensive and atherosclerotic arteries the release of endothelium-derived relaxing factors and/or the responsiveness of vascular smooth muscle cells to the relaxing factors is reduced, while that of endothelium derived contracting factors is augmented. This imbalance of endothelium-derived relaxing and contracting factors may be important in the pathogenesis of hypertension and its cardiovascular complications. PMID- 2189445 TI - Angiotensin converting enzyme inhibitors. AB - This review focuses on the use of angiotensin converting enzyme (ACE) inhibitors in hypertensive diseases. Specifically discussed are: proposed mechanisms of action, the pharmacology of the commercially available ACE inhibitors (captopril, enalapril, and lisinopril), their renal effects, and their safety and efficacy. The ACE inhibitors are assuming a dominant role in our therapeutic armamentarium, in that they are well-tolerated and very effective in the treatment of mild, moderate or severe hypertension. PMID- 2189446 TI - The neuropsychology of visual image generation: data, method, and theory. AB - This paper presents a review of the empirical evidence bearing on the localization of the image-generation process in cerebral structures and examines several issues related to the study of functional hemispheric asymmetry. In spite of recent claims that the left hemisphere is specialized for the generation of mental visual images, an examination of the relevant data and experimental procedures provides little support for this view and suggests that both hemispheres simultaneously and conjointly contribute to this process. Methodological and theoretical issues related to the localization of functions in the brain, some assumptions guiding laterality research, and computational models of cerebral lateralization are briefly discussed. PMID- 2189447 TI - Transition from maternal to embryonic control in early mammalian development: a comparison of several species. PMID- 2189448 TI - Estimating anesthetic depth by electroencephalography during anesthetic induction and intubation in patients undergoing cardiac surgery. AB - Intravenous (IV) anesthesia titrated to continuous computer-processed electroencephalograms (EEGs) was studied in 32 consecutive patients undergoing cardiac surgery. Anesthesia was induced with fentanyl 50 micrograms/kg with no EEG monitoring (n = 16) or 25 to 50 micrograms depending on changes in EEG (n = 16). EEG, oxygen saturation by pulse oximeter, intra-arterial blood pressure (BP), central venous pressure (CVP), and pulmonary artery pressure (PAP) (n = 18) were monitored continuously. Cardiac output (CO), CVP, PAP, spectral-edge frequency for each hemisphere, and BP were recorded before induction, immediately before intubation, and 1 and 5 minutes after intubation. With EEG monitoring, intubation was performed when spectral-edge frequency decreased to 10 Hz or less. Recall and pain were investigated 2 to 12 weeks postoperatively. With EEG, the amount of fentanyl used before intubation was significantly lower (39.7 +/- 2 micrograms/kg; p less than 0.005) than without EEG (50 micrograms/kg). The decrease in BP (% change) was less with than without EEG; mean changes in BP between preinduction and preintubation were -7.4% +/- 3.8% and -16.5% +/- 3.1% and between preinduction and 1 minute after intubation 0.3% +/- 3.4% and -12.5% +/- 3.5%, respectively. Percent changes in mean BP between intubation and 1 minute after were 9.6% +/- 4.0% with EEG and 5.2% +/- 3.0% without EEG. No patient in either group had recall. The authors conclude that using EEG monitoring to estimate depth of anesthesia during induction and laryngoscopy may increase safety in high-risk patients undergoing cardiac surgery. PMID- 2189449 TI - Postobstructive pulmonary edema following anesthesia. AB - Pulmonary edema developing after the relief of upper airway obstruction has been reported in association with a diversity of etiologic factors, including hanging, strangulation, tumors, foreign bodies, goiter, and laryngospasm. Since 1977, 18 cases of adults with postobstructive pulmonary edema associated with anesthesia have been reported. A case is presented of a healthy 20-year-old male who developed pulmonary edema following two episodes of acute upper airway obstruction associated with general anesthesia. Postanesthetic laryngospasm has been implicated as the most frequent cause of this syndrome in adults. Risk factors for the development of upper airway obstruction have been identified in the majority of these cases. A heightened awareness among anesthesiologists of this poorly recognized and hence often perplexing syndrome may help reduce the occurrence and facilitate the treatment of this potential complication of perioperative airway management. PMID- 2189450 TI - General versus epidural anesthesia for femoral-popliteal bypass surgery. AB - This study examines whether epidural anesthesia is more effective than general anesthesia using an inhalation agent in controlling cardiovascular responses during femoral-popliteal bypass surgery. Nineteen patients were randomized into two groups: general anesthesia (n = 10) and epidural anesthesia (n = 9). The patients who underwent general anesthesia received sodium pentothal and succinylcholine for induction of anesthesia and 60% N2O, 40% O2, and 1% to 1.5% isoflurane for maintenance. Fifteen minutes before extubation, the patients received morphine sulfate 0.05 mg/kg intravenously (IV). The group that underwent epidural anesthesia received anesthesia to T-10 (through a catheter placed in the L4-5 interspace using 3% 2-chloroprocaine). Thirty minutes after the last dose, 0.05 mg/kg IV was administered. Hemodynamic variables were recorded at selected intervals during the operation and for 60 minutes in the recovery room. In the general anesthesia group, mean arterial pressure (MAP) and rate pressure product (RPP) significantly decreased (p less than 0.05) during the operation as compared with preoperative values. Following intubation and skin incision, 5 minutes after extubation, and after 60 minutes in the recovery room, MAP, heart rate (HR), and RPP were significantly greater (p less than 0.05) as compared with intraoperative periods. In the epidural anesthesia group, there were clinically important decreases in MAP and RPP after reaching T-10 and skin incision. The general anesthesia patients showed higher MAP, HR, and RPP 5 minutes after extubation and after 60 minutes in the recovery room. Epidural anesthesia patients showed stable hemodynamic patterns throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189451 TI - Anesthesia and monitoring during whole body radiation in children. AB - During whole body radiation therapy of children, treatment may be done in places not equipped with acceptable scavenging systems for anesthetic gases and where clinical observation of the patient may be impossible. In order to solve this problem, the authors have used a total intravenous (IV) anesthetic technique using midazolam, pancuronium, and fentanyl. With midazolam as the only hypnotic agent, the problem with scavenging is solved, and a computer simulation of the plasma concentration of midazolam is presented. A modified stethoscope for monitoring during radiation also has been developed. This anesthetic technique and the stethoscope have been used in seven children. The total IV anesthesia proved to be a useful method for children during whole body radiation. The modified stethoscope functioned very well and was a useful complement to the monitoring equipment. PMID- 2189452 TI - Effects of alfentanil and lidocaine on the hemodynamic responses to laryngoscopy and tracheal intubation. AB - This study was undertaken to determine whether lidocaine and/or alfentanil can effectively abolish or attenuate the increase in mean arterial pressure (MAP), heart rate (HR), and rate pressure product (RPP) associated with rapid sequence induction of anesthesia. Sixty patients were randomly divided into four groups. Group 1 received saline 10 ml, group 2 received lidocaine 2 mg/kg, group 3 received alfentanil 15 micrograms/kg, and group 4 received alfentanil 30 micrograms/kg. All patients were induced with sodium thiopental 4 mg/kg and succinylcholine 1.5 mg/kg to facilitate tracheal intubation. The study drug was given after sodium thiopental was administered, and the investigator was blinded to it. Blood pressure (BP) and HR were recorded at the following times: before induction; after induction but before laryngoscopy and intubation; and 1, 3, and 5 minutes after intubation. Alfentanil 15 and 30 micrograms/kg given in rapid sequence fashion with thiopental and succinylcholine effectively blunted the hemodynamic responses to laryngoscopy and tracheal intubation. Lidocaine 2 mg/kg and saline were found to be ineffective in blunting these same responses. PMID- 2189453 TI - Neutrophil attractant/activation protein-1 (NAP-1 [interleukin-8]). AB - Neutrophil attractant/activation protein-1 (NAP-1 [interleukin-8]) is an 8,400 D protein that is a chemoattractant and granule release stimulus for neutrophils. NAP-1 was first purified from culture fluids of lipopolysaccharide-stimulated human blood mononuclear leukocytes. It was subsequently isolated from lipopolysaccharide-stimulated lung macrophages, mitogen-stimulated lymphocytes, and virus-infected fibroblasts. Interleukin-1 or tumor necrosis factor induces NAP-1 mRNA in many cells, including monocytes, fibroblasts, and endothelial cells. NAP-1 belongs in a family of host defense small proteins, which have a degree of sequence and structural similarity. Noteworthy are the four half cystine residues in each protein, which are in register when the protein sequences are suitably aligned. Based on cloning data and N-terminal sequence analyses, NAP-1 is secreted as a 79 residue protein after cleavage of a 20 residue signal peptide. The commonly isolated 77 and 72 residue forms are probably extracellular cleavage products. NAP-1 has considerable charge heterogeneity. Charge and length variants all have chemotactic activity. In contrast to many chemoattractants, NAP-1 does not attract monocytes. Intradermal injection of NAP-1 causes neutrophil infiltration. The wide spectrum of cell sources and production stimuli suggests that NAP-1 mediates neutrophil recruitment in host defense and disease. PMID- 2189454 TI - Molecular determinants of neutrophil adhesion. PMID- 2189455 TI - Degradation of extracellular matrix proteoglycans by human neutrophils. PMID- 2189456 TI - Interaction between chemoattractants and bacterial lipopolysaccharide in the induction and enhancement of neutrophil adhesion. AB - Chemotactic peptides in the circulation stimulate neutrophils to become sequestered in the pulmonary vasculature, and low concentrations of bacterial lipopolysaccharide (LPS) enhance and prolong this effect. This interaction of neutrophils with the vascular endothelium is thought to involve, in part, the increase in adhesiveness induced in neutrophils by such stimuli. In this study, the binding of albumin-coated latex beads to neutrophils was used to determine whether the enhancement seen with LPS results from an increase in the number of adhesive cells, from the enhancement of the adhesiveness of individual neutrophils, or both. Chemotactic peptides alone and LPS alone induced an increase both in the adhesive population and in the number of beads bound per individual neutrophil. The number of beads bound per cell increased over a very wide range of stimulus concentrations, showing that the degree of adhesiveness of an individual cell in the population varies over a considerable range. Trace concentrations of LPS (10 ng/ml or less), i.e., levels close to those measurable in vivo, had little effect on the proportion of neutrophils that were stimulated by chemotactic factor to become adhesive but did significantly enhance the number of beads bound to each individual neutrophil. The enhancement may require the presence of the CD11/18 glycoprotein complex, but was not further upregulated by LPS. No evidence could be obtained to suggest that the effect of LPS involved release of tumor necrosis factor (TNF) from the numbers of monocytes in the preparation, and the observations are consistent with a direct effect of LPS on the neutrophils. It is suggested that this increase in adhesive sites on the cell could explain the persistence of the sequestration of neutrophils in the microvasculature seen in the presence of both chemoattractants and LPS by enhancing the "strength" of the adhesion to endothelial cells. The increased adhesion may also set the stage for enhanced endothelial injury. PMID- 2189457 TI - Expression of cell-specific markers for alveolar epithelium in fetal rat lung. AB - In adults, the alveolar epithelium is composed of types I and II cells which differ structurally and functionally although they appear to belong to the same cell lineage. Using cell-specific markers (type I cells, monoclonal antibody; type II cells, Maclura pomifera lectin [MPA]), we have determined when and in what pattern their binding sites occur during development of the fetal rat lung. Rather than first appearing on days 19 to 20, when morphogenesis of type I cells occurs and lamellar bodies provide positive identification of type II cells, the markers appeared on day 15 (for type I cell marker) and day 16 (for type II cell marker). The type I cell marker was widespread by day 17 and was sufficiently abundant to be detected on a Western blot. MPA binding appeared more gradually and was often found on isolated cells. On serial sections of day 20 lung, the markers appeared to be localized to the same cells. The early appearance of cell specific markers suggests an early onset of the developmental program that leads to full differentiation of types I and II cells. Co-expression of both cell specific markers suggest that fetal cell lineage may differ from the scheme proposed by others that type II cells serve as type I cell precursors during development. PMID- 2189458 TI - Bronchial epithelial cells respond to insulin and insulin-like growth factor-I as a chemoattractant. AB - Migration of epithelial cells to cover areas of injury is thought to be important in the repair process following airway insult. Insulin is reported to be a growth factor for bronchial epithelial cells, and growth factors have been known to be chemotactic for many types of cells. Thus, we hypothesized that insulin may be a chemoattractant for bronchial epithelial cells. To evaluate this, we prepared bronchial epithelial cells and measured their chemotactic activity toward insulin. Bronchial epithelial cells were isolated by overnight digestion with bacterial protease, filtered through 100-microns nitex mesh, and then cultured at 1 x 10(6) cells/ml in tissue culture dishes in medium 199 supplemented with transferrin, insulin, epidermal growth factor, hydrocortisone, antibiotics, and 10% FCS for 3 d. The cultured cells were rinsed twice to remove supplements, trypsinized and resuspended at 1 x 10(6) cells/ml in medium 199 without supplements, and used as the cell source for chemotaxis. Chemotactic activity of bronchial epithelial cells was measured by the blindwell chamber technique using 8-microns Nuclepore filter membranes coated with 0.1% gelatin. The cells were added to the top wells in a 48-multiwell chamber with insulin in the bottom wells and incubated for 6 h at 37 degrees C, 5% CO2. Bronchial epithelial cells migrated in response to insulin in a dose-dependent manner up to an optimal dose of insulin, 100 micrograms/ml, and decreased at higher concentrations. The number of migrated cells per 10 high power fields was 33.7 +/- 1.9 at the optimum and 3.7 +/- 0.7 without insulin (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189459 TI - Applications of magnetic resonance imaging to gynecology. AB - The advent of MRI has improved the ability of the diagnostic radiologist to provide useful clinical information to the practicing gynecologist. Although US remains the screening procedure of choice for evaluation of the uterus and adnexa because of its relative safety and low cost, MRI is now considered the next imaging step. In a woman with pelvic pain, MRI can accurately identify adenomyosis, enumerate and localize uterine fibroids, and provide more accurate identification of endometriosis and cystic teratomas of the ovary than US. Although MRI should not be used as a screening procedure for diagnosing endometrial or cervical carcinoma, it can aid in patient management by determining the extent of myometrial or cervical invasion by endometrial carcinoma and can be used to calculate tumor volume in patients with cervical carcinoma. Early studies suggest that MRI may be helpful in distinguishing between long-term radiation fibrosis and tumor recurrence in such patients. MRI findings may be highly indicative of the presence of ovarian malignancy, but the procedure adds little to CT or US findings. Nevertheless, MRI is superior in the localization of pelvic masses and is often indicated in clarifying the origin of a mass as uterine or ovarian. PMID- 2189460 TI - Magnetic resonance imaging of the prostate and bladder. AB - Prostate carcinoma is the most common cancer in men and the second most lethal malignancy among the American male population. Nevertheless, it is potentially curable if detected early and treated appropriately. Treatment options vary depending on the extent (stage) of the cancer. MRI has no role as a screening method for prostatic carcinoma because it is expensive, time consuming, and unable to differentiate benign from malignant disease, but it can detect early prostatic cancers in patients with known tumor and can accurately stage these tumors. MRI is becoming the imaging modality of choice for local staging of prostate cancer and is rapidly replacing CT and ultrasonography for this purpose. Treatment protocols for bladder carcinoma also depend on the stage of the tumor. Clinical staging of bladder cancer has been limited. MRI is as good as or better than CT in bladder tumor staging when extravesical tumor involvement is present. MRI also has the potential to become useful in determining the depth of wall invasion in tumors confined to the bladder. PMID- 2189461 TI - [Atherosclerosis and cardiovascular risk factors in the elderly]. AB - Atherosclerosis is an age-related process that reflects the interaction between aging and the factors that influence the rate of atherogenesis. The great difficulty in the study of the cardiovascular consequences of aging is due to the fact that it is not easy to distinguish between the effects aging per se (primary aging) and the effects of changes in behaviour and life style that usually accompany old age and may influence the rate of atherogenesis. Most risk factors known to contribute to cardiovascular disease are highly prevalent in the aged and all of them are modifiable. Ideally, preventive measures should be initiated early in the life, when such measures however instituted in the aged, also have beneficial effects. Because incidence rates of atherosclerotic disease are high in the elderly, preventive measures could have a great impact on older persons. Thus interventions aimed to decrease cardiovascular morbidity and mortality will reduce the health costs and improve the quality of the last years of life. PMID- 2189463 TI - [Silent ischemia. To treat or not to treat?]. AB - Silent myocardial ischaemia can be defined as the presence of transient ischaemic alterations in absence of angina. Those include metabolic, functional, electrocardiographic and anatomic abnormalities without typical chest pain. Its incidence, prognostic significance, possible identification in clinical practice as well as need for treatment varies according to the group of patients. In the present review, we discuss these concepts in base of the knowledge supported by the results of different studies. As a rule, the incidence, prognostic significance, and henceforth the need for its identification, increase from the low risk groups of patients to those of high risk according to classical criteria. To this respect, it is useful to differentiate three groups of patients: normal subjects, stable coronary heart disease and unstable heart disease. Medical treatment with anti-ischaemic drugs as well as myocardium revascularization procedures have shown to decrease the incidence and severity of silent myocardial ischaemia, but its influence on prognosis is unknown, and it should be emphasized that the main objective in the treatment of silent ischaemia is improve prognosis. PMID- 2189462 TI - Ischemic myocardial cell necrosis: calcium overload or oxygen free-radicals? AB - Myocardial ischemia results from imbalance between the needs of cardiac tissue and oxygenated blood supplied by the coronary circulation. This imbalance causes a deficit in tissue supplies of oxygen and of metabolizable substrates which leads, to varying degrees according to the severity of the ischemic process, to a decrease in the production of energy. This production rapidly becomes insufficient to ensure normal function. Furthermore, the accumulation of metabolic waste products causes the development of progressive cellular acidosis with inhibitory functional and metabolic effects. These metabolic and functional changes in the cell are accompanied by changes in structure and arrhythmias, as well as modifications in all-energy dependent mechanisms, particularly clearly marked in relation to membrane systems responsible for ion transport. The degree of these various disturbances is dependent upon the severity of the ischemic process as well as its duration. Reversibility can be ensured if normal perfusion is restored early. If reperfusion occurs later, it is generally incapable of ensuring the recovery of normal cell function and the ischemic cell is then destined to necrosis. Among the possible factors responsible for irreversible ischemic injury, an increase in cellular free-calcium concentration or an over production of oxygen free-radicals, have been largely suggested. A number of therapeutic measures (metabolic or pharmaceutical) have been suggested with the aim of prolonging the duration of tolerable ischemia before the development of irreversible changes which render reperfusion ineffective. This is particularly the case of anti-ischemic drugs, the prototype of which is for instance trimetazidine. PMID- 2189464 TI - Radionuclide studies in the evaluation of ischemic heart disease. AB - In recent years, radionuclide studies have gained an important place in the evaluation of ischemic heart disease, be it as diagnostic procedures, as predictors of prognosis or for evaluation of therapy. For diagnostic purposes, myocardial perfusion studies using thallium-201 or newer technetium-99m bound perfusion agents have been used as well as radionuclide angiocardiography both at rest and during exercise/stress. Used in a Bayesian approach, these methods yield the highest diagnostic accuracy in patients with a 30% to 70% pre-test likelihood of disease, i.e. in the clinically difficult patients with atypical chest pain and/or non-specific ECG changes. In addition, scintigraphic studies have proved valuable in the setting of silent ischemia and acute myocardial infarction. These methods provide not only a yes/no answer to our diagnostic questions but allow one to assess severity, extent and localization of coronary artery disease. Portable devices are now being constructed which allow continuous ambulatory monitoring of left ventricular function by scintigraphic techniques. PMID- 2189465 TI - Color duplex sonography of extremity veins. PMID- 2189466 TI - Duplex and color-flow imaging of the lower extremity arterial circulation. PMID- 2189467 TI - Color-Doppler imaging. PMID- 2189468 TI - Color duplex imaging and Doppler spectrum analysis: principle, capabilities, and limitations. PMID- 2189469 TI - Duplex examination of the carotid arteries. PMID- 2189470 TI - [Medical treatment of cholelithiasis. I. Bile acids]. AB - Gallstones constitute an important health problem for its prevalence and the cost of its definitive treatment, cholecystectomy. Thus, medical therapy is a necessary and desirable goal. In this study the different means for the non surgical treatment of gallstones are reviewed. In this first part the pharmacological basis is described as well as the selection of patients. The litholytic mechanism of bile acids, its efficacy and the causes of therapeutic failure are describe. PMID- 2189471 TI - Medical management of trigeminal neuralgia. AB - Trigeminal neuralgia is a sudden, severe, brief, recurrent stabbing pain in the distribution of the trigeminal nerve whose aetiology remains unknown. Medical management is the first line of treatment and when this fails, surgical treatment needs to be undertaken. Carbamazepine is the best anti-neuralgic drug available at present, but may cause unacceptable side-effects. Phenytoin, baclofen and clonazepam are other drugs used, either as monotherapy or together with carbamazepine, but they are not as effective. Oxcarbazepine, a new drug, similar to carbamazepine but with fewer side-effects, may prove to be the drug of the future. Once diagnosed, these patients should be managed by specialists who can offer a range of treatments. PMID- 2189472 TI - The use of extra-oral traction with removable appliances. AB - Extra-oral traction has two main applications in orthodontic treatment. It may be used to prevent forward movement of anchor teeth and also to provide a force for distalisation of molars, and/or buccal segments. If correctly applied, EOT can help to ease problems in a difficult treatment and make possible an otherwise impossible treatment plan. PMID- 2189473 TI - Treatment of Hodgkin's disease. AB - The available data support the hypothesis proposed by Smithers that Hodgkin's disease appears to be a systemic disorder of the lymphatic system. Standard treatments have been developed that cure approximately 70% of all patients who present to most institutions. Physicians should know the treatment approaches before proceeding with staging, because intelligent use of the best available treatment often obviates the need for staging laparotomy. At present, it is best that either chemotherapy or radiotherapy be used alone, except in patients who have massive mediastinal disease and for whom combinations of radiotherapy and combination chemotherapy are superior. Despite the long series of clinical trials conducted over the past two decades, no combination of four drugs has improved the results obtained with the original mechlorethamine-vincristine-procarbazine prednisone program, when it is given in sufficient doses. It has been assumed that drug resistance of a specific type was the major reason for treatment failure. Attempts by physicians to overcome drug resistance, using alternating cyclical non-cross-resistant combination chemotherapy, have thus far not proved this approach to be superior to the use of a four-drug combination in full doses, and call into question this approach to testing the Goldie-Coldman hypothesis. Dose intensity has been a poorly controlled variable in virtually all clinical trials in Hodgkin's disease, and inadequate dosing may be the prime reason for treatment failure. This point has been highlighted by recent excellent results with marrow-ablative, high-dose chemotherapy and autologous bone marrow transplantation support for patients with very advanced "drug-resistant" disease. Investigators are now attempting to improve dose intensity by using more concentrated versions of standard drug combinations with colony-stimulating factors for support. PMID- 2189475 TI - Salvage therapy for patients with non-Hodgkin's lymphoma. AB - The non-Hodgkin's lymphomas represent a diverse group of lymphoproliferative disorders for which treatment must be specified according to the patient's status as well as the disease status. Although many advances have been made in the front line treatment of non-Hodgkin's lymphomas, more than 50% of the patients will not be cured with their initial therapy. Because of these treatment failures with front-line therapy, many different salvage therapies have been tried in this patient population. In this article, we describe several conventional-dose, salvage chemotherapies and strategies for dose escalation and hematopoietic stem cell transplantation in an attempt to overcome chemotherapy resistance. PMID- 2189474 TI - Treatment of patients with aggressive lymphomas: an overview. AB - The treatment of aggressive lymphomas has progressed to the point that over 90% of the patients with localized disease, around 50% of the patients with advanced disease, and perhaps up to 25% of relapsing patients may enjoy long-term, disease free survival. Several studies have documented that primary combination chemotherapy with or without involved-field radiation therapy is capable of curing 90% or more of the patients with clinically staged, localized disease. Results with primary radiation therapy in such patients are not nearly as good, even in those who undergo laparotomy staging. The management of advanced-stage disease is more controversial. Although combination chemotherapy is the treatment of choice, there is debate about whether the impressive results with the latest regimens, such as MACOP-B, COP-BLAM III, and ProMACE-CytaBOM, which appear to be curative for around 60% or more of advanced-stage patients, are really superior to CHOP, the most widely used program, which cures about 30% or so of the patients. A major idea that is guiding the development of new treatment programs is augmenting the dose intensity of the treatment. This notion is fueled not only by the demonstrated dose-response relationships that have been documented by Hryniuk and colleagues in other tumor types, such as cancers of the breast, ovary, and colon, but also by recent experience in the salvage therapy of relapsed aggressive lymphoma. Formerly a universally fatal disease, relapsed aggressive lymphoma now appears to be responsive to high-dose chemotherapy with or without radiation therapy followed by autologous or allogeneic bone marrow or peripheral blood stem cell reconstitution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189476 TI - Acquired immunodeficiency syndrome-associated lymphomas. AB - Congenital and acquired states of immunodeficiency have long been associated with an increased incidence of malignant lymphoma. An increased incidence of non Hodgkin's lymphomas was recognized early in the epidemic immunodeficiency state associated with the human immunodeficiency virus (HIV) infection AIDS. Although the precise etiologic mechanism of these lymphomas remains speculative, the presence of Epstein-Barr viral proteins or sequences and characteristic chromosomal translocations giving rise to altered expression of the c-myc oncogene have frequently been observed. It has been suggested that HIV infection leading to disordered T-lymphocyte function (possibly in conjunction with Epstein Barr infection) leads to the emergence of polyclonal populations of stimulated B lymphocytes. These cells, which undergo physiologic immunoglobulin gene rearrangement, may provide the background for the occurrence of characteristic chromosomal translocations that lead to the emergence of malignant lymphomas. These lymphomas tend to present clinically with high-grade histopathologic subtype, advanced stage, and a propensity for the involvement of otherwise unusual extranodal sites, including the central nervous system. The experience with therapy for HIV-associated lymphomas has indicated that highly aggressive, dose-intensive chemotherapy regimens may be associated with inferior results. More recent regimens have stressed less myelosuppressive therapy combined with prophylaxis for central nervous system disease and pneumocystis infection. The dominant prognostic factors in the HIV-associated lymphomas appear to be primarily related to the underlying HIV infection and include total CD4 lymphocyte count, performance status, and prior AIDS diagnosis. PMID- 2189477 TI - Late complications of Hodgkin's disease management. AB - In the past several decades, Hodgkin's disease has been transformed from a uniformly fatal illness to one that can be treated with the expectation of long term remission or cure in the majority of patients. Because patients now survive for long periods after curative intervention, various complications have been identified. The spectrum of complications following curative therapy is quite diverse and includes immunologic, cardiovascular, pulmonary, thyroid, and gonadal dysfunction. In addition, second malignant neoplasms in the form of acute leukemia as well as secondary solid tumors have now been documented to occur with increased frequency in patients cured of Hodgkin's disease. PMID- 2189479 TI - Cytogenetics of non-Hodgkin's lymphoma. AB - In the non-Hodgkin's lymphoma (NHL), recurring cytogenetic abnormalities have been identified, and significant correlations among them and morphology, immunophenotyping, and parameters of clinical outcome have been recognized. The structural involvement of the 14q32 band is substantially more frequent than are other common abnormalities, which include del(6q), i(17q), +3, +7, +12, +18, and +21. Twenty-two recurring translocations have been identified. Almost three fourths of all breakpoints in NHL occur at sites to which lineage-determining, transformation-related genes, or fragile sites have been mapped. Besides the well known association of the t(14;18) (q32;q21) with the follicular histologies and t(8;14)(q24;q32) with small non-cleaved cell lymphoma, several other associations between recurring cytogenetic abnormalities and morphologic subtypes have been found. Similarly, several associations between cytogenetic abnormalities and the B or T immunophenotype have been delineated. Trisomy 3 or duplications of 3p predict a favorable clinical outcome; trisomy 2 or duplication 2p and abnormalities of chromosome 17 predict a poor prognosis. Common sequential changes include a (second) 14q32 break and abnormalities of chromosomes 1 and 2. Continuing work in these areas will serve to identify more clearly those regions of the genome important to transformation, differentiation, clinical aggressiveness, and progression in NHL. PMID- 2189478 TI - Prospects for interleukin-2 therapy in hematologic malignant neoplasms. AB - Interleukin-2 (IL-2) is a regulator of diverse functions of the immune system that can induce regressions in some experimental and human tumors. These early findings suggest a potential role for IL-2 in the treatment of certain malignant neoplasms including lymphomas and leukemias. Advanced, rapidly growing tumors are generally not amenable to immunotherapy. Therefore, it is more likely that protocols with IL-2 will be used to prolong remission and prevent relapse in leukemia patients with minimal tumor load. Several approaches are currently being tested in animal experiments and clinical trials. Activation of tumor-reactive lymphocytes (specific or nonspecific) by IL-2 in vivo may eradicate residual leukemia in patients with occult disease. In vitro-propagated autologous or allogeneic leukemia-reactive T cells may be infused with IL-2 to facilitate the tumor destruction. The IL-2 enhances monoclonal antibody-dependent effector systems, such as antibody-dependent cell-mediated cytotoxicity in vivo. Monoclonal antibodies recognizing epitopes on leukemia/lymphoma cells could therefore be used with IL-2 to target nonspecific effectors to destroy tumor cells. Other cytokines appear to potentiate various antitumor activities of IL-2, including cytotoxicity of antigen-specific T lymphocytes or lymphokine-activated killer cells in vitro, and these combined effects may be exploited in clinical trials in which more than one cytokine is used simultaneously or in sequence. Finally, a stepwise completion of clinical protocols testing this immunologic approach in combination with other treatment modalities is necessary.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189480 TI - Brain, behavior, and immunity: an interactive system. AB - The immune, neuroendocrine, and central nervous systems are stimulus response systems that are similar in the functions they subserve and tightly integrated in their actions. The reciprocal regulatory effects of these systems provide a basis (but not proof) for the belief that brain-immune interactions are of clinical relevance and not reducible to characteristics of component systems. In this paper, evidence for the integration and mutual regulation of central nervous and immune systems is reviewed. Additionally, behavioral and time-dependent neuroendocrine effects of interleukin-2 are presented in detail. PMID- 2189481 TI - Potential mistakes in hip-joint sonography. AB - The growing propagation of hip-joint sonography and its increasing use as a screening method make it important to point out some potential mistakes. Good image quality, three-dimensional evaluation with real-time technique, consideration of form variants, correct estimation of angle parameters, consideration of medical history, and clinical evaluation as well as the necessity of follow-up examinations are inevitable requirements for reliable diagnostic sonography of the hip joint. PMID- 2189482 TI - Current evaluation of sonography of the meniscus. Results of a comparative study of sonographic and arthroscopic findings. AB - Sonography of the knee has gained in significance in the diagnosis of the meniscus; experimental and clinical studies have demonstrated that the normal and pathological anatomy of the meniscus can be visualized on a sonogram. The aim of this comparative investigation is to evaluate sonographic lesion diagnosis in comparison with arthroscopic findings, using a standardized examination method. Two hundred and six knee joints were first scanned sonographically using a 7.5 MHz sector transducer. The examining doctor had neither anamnestic nor clinical information in advance. On the following day, the joints were examined arthroscopically, without the findings of the day before being available to the examiner. When the findings were compared, the sensitivity of sonographic diagnosis of lesions was found to be 82.2% and its specificity 87.6%. The patients were of varying ages and had varying anamneses. The results show that sonography of the meniscus is a valuable diagnostic help when the knee-joint symptoms are not clear, given that the correct technical equipment and sufficient experience with this form of examination are at hand. The advantage of sonography is that, in contrast to arthroscopy, it is noninvasive and easily available. PMID- 2189483 TI - Arthroscopic cartilage debridement by excimer laser in chondromalacia of the knee joint. A prospective randomized clinical study. AB - A new operative technique in arthroscopic treatment of chondromalacia using ultraviolet laser systems is introduced. The postoperative results are evaluated in a prospective and randomized clinical trial. One hundred and forty patients stage II or III chondromalacia according to Outerbridge were randomly assigned to arthroscopic operation using either laser or mechanical instruments. After a 6 month follow-up period the clinical results were compared, guided by a specially designed modification of the Lysholm scoring scale. In the short-term follow-up laser surgery gave superior results in regard to reducing pain (P less than 0.05) and leading to a lower incidence of reactive synovitis (P less than 0.01). No difference was found in respect of disability and functional impairment. Our results lead to the conclusion that arthroscopic laser application seems to be a successful procedure in the treatment of degenerative cartilage disorders, providing precise ablation of tissue without significant thermal damage to the remaining cartilage. PMID- 2189484 TI - Bilateral posterior pendulum dislocation of the shoulder. Case report and review of the literature. AB - A 20-year-old patient with bilateral voluntary and involuntary dislocation of both shoulders is reported on. There was no history of significant trauma, no systemic hypermobility of joints, no signs of neurological or psychological problems, and no evidence of joint disease. According to Reischauer's classification of shoulder instabilities, the patient suffered from bilateral posterior pendulum dislocations of his shoulders. The literature is reviewed and different classifications of shoulder instability and the underlying pathology of voluntary and involuntary shoulder dislocations are discussed. After ruling out the possibility of psychological problems, we performed an operative stabilization by arthroscopic means. At 1-year follow-up the patient reported no recurrence, good shoulder musculature, and no disability at work. This result confirms the unsuspicious psychological evaluation and our therapeutic management. PMID- 2189485 TI - Irreducible dorsal dislocation of the metatarsophalangeal joint of the hallux. AB - Irreducible dorsal dislocation of the metatarsophalangeal joint of the hallux is a rare injury. A case is presented and the literature is reviewed, with emphasis on pathomechanics and treatment alternatives. PMID- 2189486 TI - Drug sensitivity assays in leukaemia and lymphoma. PMID- 2189487 TI - Acute 'bilineal-biphenotypic' leukaemia. AB - We describe a unique case of hybrid leukaemia with bilineal and biphenotypic features. The coexistence of lymphoblasts and monoblasts was determined morphologically and cytochemically. Immunofluorescence and immunohistochemical analysis revealed that each blast population had both T lymphoid (CD2, cytoplasmic CD3) and myeloid (CD11, CD13, CD15) markers. Southern blot analysis of DNA extracted from the lymph node biopsy demonstrated the presence of monoclonal rearrangement of the TcR-C beta gene. Cytogenetic analysis of the bone marrow cells showed a karyotype of 48, XY, 7q+ in all of the metaphases examined. These observations are suggestive of a monoclonal origin for these two distinct blast populations. PMID- 2189488 TI - Ras activation in myelodysplastic syndromes: clinical and molecular study of the chronic phase of the disease. AB - We studied N-ras and Ki-ras point mutations respectively at codons 12-13 and 12 in 15 patients with myelodysplastic syndromes (MDS) using the polymerase chain reaction (PCR) method for DNA amplification, and slot blot hybridization to allele specific oligonucleotide (ASO) probes. We analysed peripheral blood and bone marrow samples collected at diagnosis and repeatedly during the chronic phase of the disease to define when the activation occurred and in which haemopoietic cell populations, in order to establish possible relationships between clinical and molecular features. In three cases the N-ras oncogene was mutated at codon 12 in every cell population, both at diagnosis and throughout the chronic phase. Point mutations were not seen at the 12 codon of the Ki-ras oncogene. In patients lacking activated ras oncogene at diagnosis, mutations were not discovered during the entire period of observation. Therefore in our cases disease progression and leukaemic transformation did not correlate with the presence of the activated N-ras. Our data suggest that ras activation occurs early in the pathogenesis of MDS and involves a haemopoietic progenitor with multiple differentiative capacity, without however conferring an apparent proliferative advantage on its progeny. PMID- 2189489 TI - Hypercoagulability during L-asparaginase treatment: the effect of antithrombin III supplementation in vivo. AB - To evaluate the occurrence of hypercoagulability during treatment with L asparaginase (L-ase), thrombin-antithrombin complex (TAT) and D-dimer levels in plasma were serially measured in 15 consecutive adult patients with acute lymphoblastic leukaemia or lymphoblastic lymphoma who had recently completed a chemotherapy cycle with cytosine arabinoside and methotrexate. The first eight patients (group A) received i.v. L-ase alone (20,000 U/m2 on alternate days over 10 d); the last seven patients (group B) received, in addition to L-ase, bolus injection of antithrombin concentrate (2000 U) on alternate days for a total of six administrations, beginning with the second L-ase infusion. Increased levels of TAT (P less than 0.05) and D-dimer (P less than 0.01) were observed prior to L ase, possibly related to inflammation and cytolysis secondary to previous chemotherapy. In patients treated with L-ase alone, further elevation of TAT (P less than 0.05) and persistence of increased D-dimer were observed, associated with marked reduction of the anticoagulant activities of protein C, protein S and antithrombin III. At variance, in patients receiving antithrombin III supplementation there was no increase of TAT and a normalization of D-dimer levels occurred during L-ase treatment. In these patients, mean plasma antithrombin III activity was maintained at levels higher than 70% of normal throughout the treatment. The rate of decline of fibrinogen, factor IX, protein C and protein S was unaffected by antithrombin III supplementation, indicating that hypercoagulability has little if any relevance for the reduction of coagulation factors and inhibitors induced by L-ase treatment. The usefulness of antithrombin III concentrates in preventing thromboembolic complications in patients submitted to L-ase treatment remains to be determined. PMID- 2189490 TI - A comparative evaluation of assays for markers of activated coagulation and/or fibrinolysis: thrombin-antithrombin complex, D-dimer and fibrinogen/fibrin fragment E antigen. AB - Measurements were made of levels of D-dimer in plasma and serum, thrombin antithrombin complex (TAT) in plasma and fibrinogen/fibrin fragment E antigen (FgE) in serum in a normal healthy control group and in patients with a range of disorders associated with hypercoagulability. Levels were determined in 31 normal healthy controls, 30 patients with disseminated intravascular coagulation (DIC), 21 patients with deep venous thrombosis (DVT), 27 patients with myocardial infarction (MI), 26 patients with acute leukaemia and 56 patients with liver disease. Considering all subjects, significant correlations were established between the results of all assays. Notably high correlations (r greater than 0.9) were established between plasma and serum levels of D-dimer, between plasma levels of D-dimer and serum levels of FgE, and between serum levels of D-dimer and FgE. All assays showed very high discrimination (sensitivity) between the normal control group and patients with DIC (97-100%), but there were marked differences between the assays in sensitivity for DVT and MI. In general, the FgE assay was more sensitive than the D-dimer assay, whilst both the FgE and D-dimer assays were more sensitive than the TAT assay. The same trends were apparent in the capability of the assays to discriminate between the normal control group and patients with acute leukaemia and liver disease: disorders with an unknown prevalence of activation of coagulation/fibrinolysis. Our results indicated that measurements of fibrinogen/fibrin degradation products (FDPs) in serum were almost unaffected by artefacts. The data further suggested that the broad spectrum FgE assay was better than the more specific D-dimer assay in detecting clinical hypercoagulability. Our study showed that, in the clinical conditions examined, FDPs were more effective markers of hypercoagulability than TAT. PMID- 2189491 TI - Unrestricted growth of Plasmodium falciparum in microcytic erythrocytes in iron deficiency and thalassaemia. AB - The mechanism(s) underlying the apparent resistance to malaria in certain inherited red cell disorders and iron deficiency anaemia remain poorly understood. The possibility that microcytic erythrocytes might inhibit parasite development, by physical restriction or reduced supply of nutrients, has been considered for many years, and never formally investigated. We sought to determine whether in vitro growth studies of P. falciparum could provide evidence to suggest that small red cell size contributes to malaria resistance in those red cell disorders in which microcytosis is a characteristic feature. Invasion and development of P. falciparum in iron deficient red cells (mean values for mean cell volume [MCV] 66 fl, mean cell haemoglobin [MCH] 19 pg) and in the red cells of two gene deletion forms of alpha-thalassaemia (mean MCV 71 fl, MCH 22 pg) were normal, assessed both morphologically, and by 3H-hypoxanthine incorporation. Although parasite appearances were normal in all cell types, morphological abnormalities were noted in iron deficient and thalassaemic cells parasitized by mature stages of P. falciparum, notably cellular ballooning and extreme hypochromia of the red cell cytoplasm. Using electron microscopy, the red cell cytoplasm in parasitized thalassaemic cells showed reduced electron density and abnormal reticulation. Normal invasion rates were observed following schizogony in microcytic cells of both types. Our findings indicate that whilst minor morphological abnormalities may be detected in parasitized iron deficiency and thalassaemic erythrocytes, development of P. falciparum in these conditions is not limited by small erythrocyte size. PMID- 2189492 TI - Haemoglobin alpha 2 beta 2 23Val----Ile produced in Escherichia coli facilitates Hb S polymerization. AB - The doubly substituted variant Hb S-Antilles (beta 6 Glu----Val, beta 23 Val--- Ile) produces sickling in heterozygous carriers. The Csat value for pure deoxyHb S-Antilles is nearly half that of deoxyHb S. Dilute solutions of pure Hb S Antilles have a lower oxygen affinity than those of Hb A or Hb S. The mutant Hb alpha 2 beta 2 23 Val----Ile was synthesized in E. coli. It exhibits a decreased oxygen affinity compared to Hb A and does not polymerize in 1.8 M phosphate buffer. Mixtures of equal amounts of Hb S + Hb beta 23 Val----Ile have a decreased Csat value compared to mixtures of Hb S + Hb A. The beta 23 Val in Hb S contributes to the axial contact joining molecules in each single filament. Substituting Ile for Val at this site increases the strength of this contact through hydrophobic interactions, allowing increased stability of the lateral contact between filaments in pair, which is the specific unit structure of polymers in deoxyHb S. PMID- 2189493 TI - Erythropoietin production in kidney tubular cells. AB - The erythropoietin gene has been cloned in three mammalian species including man and recombinant erythropoietin is now used to treat the anaemia of chronic renal failure. Despite the isolation of the gene the precise cellular location of erythropoietin synthesis remains controversial. We present studies which demonstrate erythropoietin production by kidney tubular cells. Erythropoietin gene expression (messenger RNA) was detected by in situ hybridization using an oligonucleotide gene probe and the translated protein product by immunohistochemistry employing antibodies raised to pure recombinant DNA derived erythropoietin. PMID- 2189494 TI - Fatty acylated proteins as components of intracellular signaling pathways. AB - From the studies presented above, it is obvious that fatty acylation is a common modification among proteins involved in cellular regulatory pathways, and in certain cases mutational analyses have demonstrated the importance of covalent fatty acids in the functioning of these proteins. Indeed, certain properties provided by fatty acylation make it an attractive modification for regulatory proteins that might interact with many different substrates, particularly those found at or near the plasma membrane/cytosol interface. In the case of intracellular fatty acylated proteins, the fatty acyl moiety allows tight binding to the plasma membrane without the need for cotranslational insertion through the bilayer. For example, consider the tight, salt-resistant interaction of myristoylated SRC with the membrane, whereas its nonmyristoylated counterpart is completely soluble. Likewise for the RAS proteins, which associate weakly with the membrane in the absence of fatty acylation, while palmitoylation increases their affinity for the plasma membrane and their biological activity. Fatty acylation also permits reversible membrane association in some cases, particularly for several myristoylated proteins, thus conferring plasticity on their interactions with various signaling pathway components. Finally, although this has not been demonstrated, it is conceivable that covalent fatty acid may allow for rapid mobility of proteins within the membrane. Several questions remain to be answered concerning requirements for fatty acylation by regulatory proteins. The identity of the putative SRC "receptor" will provide important clues as to the pathways in which normal SRC functions, as well as into the process of transformation by oncogenic tyrosine kinases. The possibility that other fatty acylated proteins associate with the plasma membrane in an analogous manner also needs to be investigated. An intriguing observation that can be made from the information presented here is that at least three different families of proteins involved in growth factor signaling pathways encode both acylated and nonacylated members, suggesting that selective fatty acylation may provide a means of determining the specificity of their interactions with other regulatory molecules. Further studies of fatty acylated proteins should yield important information concerning the regulation of intracellular signaling pathways utilized during growth and differentiation. PMID- 2189496 TI - Oxalyl hydroxamates as reaction-intermediate analogues for ketol-acid reductoisomerase. AB - N-Hydroxy-N-isopropyloxamate (IpOHA) is an exceptionally potent inhibitor of the Escherichia coli ketol-acid reductoisomerase. In the presence of Mg2+ or Mn2+, IpOHA inhibits the enzyme in a time-dependent manner, forming a nearly irreversible complex. Nucleotide, which is essential for catalysis, greatly enhances the binding of IpOHA by the reductoisomerase, with NADPH (normally present during the enzyme's rearrangement step, i.e., conversion of a beta-keto acid into an alpha-keto acid, in either the forward or reverse physiological reactions) being more effective than NADP. In the presence of Mg2+ and NADPH, IpOHA appears to bind to the enzyme in a two-step mechanism, with an initial inhibition constant of 160 nM and a maximum rate of formation of the tight, slowly reversible complex of 0.57 min-1 (values that give an association rate of IpOHA, at low concentration, of 5.9 X 10(4) M-1 s-1). The rate of exchange of [14C]IpOHA from an enzyme-[14C]IpOHA-Mg2(+)-NADPH complex with exogenous, unlabeled IpOHA has a half-time of 6 days (150 h). This dissociation rate (1.3 X 10(-6) s-1) and the association rate determined by inactivation kinetics define an overall dissociation constant of 22 pM. By contrast, in the presence of Mn2+ and NADPH, the corresponding association and dissociation rates for IpOHA are 8.2 X 10(4) M-1 s-1 and 3.2 X 10(-6) s-1 (half-time = 2.5 days), respectively, which define an overall dissociation constant of 38 pM. In the presence of NADP or in the absence of nucleotide (both in the presence of Mg2+), the enzyme-IpOHA complex is far more labile, with dissociation half-times of 28 and 2 h, respectively. In the absence of Mg2+ or Mn2+, IpOHA does not exhibit time dependent inhibition of the reductoisomerase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189495 TI - Active site of mercuric reductase resides at the subunit interface and requires Cys135 and Cys140 from one subunit and Cys558 and Cys559 from the adjacent subunit: evidence from in vivo and in vitro heterodimer formation. AB - Mercuric reductase catalyzes the two-electron reduction of Hg(II) to Hg(0) using NADPH as the reductant; this reaction constitutes the molecular basis for detoxification of Hg(II) by bacteria. The enzyme is an alpha 2 homodimer and possesses two pairs of cysteine residues, Cys135 and Cys140 (redox-active pair) and Cys558 and Cys559 (C-terminal pair), which are known to be essential for catalysis. In the present study, we have obtained evidence for an intersubunit active site, consisting of a redox-active cysteine pair from one subunit and a C terminal pair from the adjacent subunit, by reconstituting catalytic activity both in vivo and in vitro starting with two inactive, mutant enzymes, Ala135Ala140Cys558Cys559 (AACC) and Cys135Cys140Ala558Ala559 (CCAA). Genetic complementation studies were used to show that coexpression of AACC and CCAA in the same cell yielded an HgR phenotype, some 10(4)-fold more resistant than cells expressing only one mutant. Purification and catalytic characterization of a similarly coexpressed protein mixture showed the mixture to have activity levels ca. 25% those of wild type; this is the same as that statistically anticipated for a CCAA-AACC heterodimeric/homodimeric mixture with only one functional active site per heterodimer. Actual physical evidence for the formation of active mutant heterodimers was obtained by chaotrope-induced subunit interchange of inactive pure CCAA and AACC homodimers in vitro followed by electrophoretic separation of heterodimers from homodimers. Taken together, these data provide compelling evidence that the active site in mercuric reductase resides at the subunit interface and contains cysteine residues originating from separate polypeptide chains. PMID- 2189497 TI - Use of a site-directed triple mutant to trap intermediates: demonstration that the flavin C(4a)-thiol adduct and reduced flavin are kinetically competent intermediates in mercuric ion reductase. AB - A mutant form of mercuric reductase, which has three of its four catalytically essential cysteine residues replaced by alanines (ACAA: Ala135Cys140Ala558Ala559), has been constructed and used for mechanistic investigations. With disruption of the Hg(II) binding site, the mutant enzyme is devoid of Hg(II) reductase activity. However, it appears to fold properly since it binds FAD normally and exhibits very tight binding of pyridine nucleotides as is seen with the wild-type enzyme. This mutant enzyme allows quantitative accumulation of two species thought to function as intermediates in the catalytic sequence of the flavoprotein disulfide reductase family of enzymes. NADPH reduces the flavin in this mutant, and a stabilized E-FADH- form accumulates. The second intermediate is a flavin C(4a)-Cys140 thiol adduct, which is quantitatively accumulated by reaction of oxidized ACAA enzyme with NADP+. The conversion of the Cys135-Cys140 disulfide in wild-type enzyme to the monothiol Cys140 in ACAA and the elevated pKa of Cys140 (6.7 vs 5.0 in wild type) have permitted detection of these intermediates at low pH (5.0). The rates of formation of E-FADH- and the breakdown of the flavin C(4a)-thiol adduct have been measured and indicate that both intermediates are kinetically competent for both the reductive half-reaction and turnover by wild-type enzyme. These results validate the general proposal that electrons flow from NADPH to FADH- to C(4a)-thiol adduct to the FAD/dithiol form that accumulates as the EH2 form in the reductive half-reaction for this class of enzymes. PMID- 2189498 TI - Mapping the effector region in Thermus thermophilus elongation factor Tu. AB - Native elongation factor Tu from Thermus thermophilus is initially attacked by various endoproteases in a region spanning amino acid residues 40-70. By comparing the hydrolysis rates of nucleotide-free and GDP-bound EF-Tu, only a small difference was observed for the tryptic cleavage at Arg-59. Protease V-8 attacks Glu-55 only in a GDP/GTP form, whereas this enzyme exclusively hydrolyze Asn-64 in nucleotide-free EF-Tu, even when the protein had been previously cleaved at Arg-59. Binding of GDP leads to a 42-fold decreased rate of hydrolysis by the Lys-C protease at Lys-52. It also reduces the accessibility of Lys-275 to trypsin, reflecting a "long-range" effect from nucleotide binding domain I to domain II. Only slight differences were observed in the rate of hydrolysis at all positions in the GDP- versus the GTP-bound form. The intrinsic GTPase activity was slightly reduced in trypsin-treated EF-Tu, significantly impaired in EF-Tu cleaved at Lys-52, and completely abolished in EF-Tu cleaved at Asn-64. No ribosome-induced GTPase activity was observed for protease-cleaved EF-Tu's. Treatment of these proteins with periodate-oxidized GDP or GTP followed by cyanoborohydride led to covalent modification of the new N-terminus located exclusively within region 52-60. The highest reactivity was shown by the N terminus of Glu-56. Additionally, lysine residues in the native protein sensitive to affinity labeling [Peter, M.E., Wittmann-Liebold, B., & Sprinzl, M. (1988) Biochemistry 27, 9132-9139] lost their reactivity upon cleavage of EF-Tu in region 52-60, suggesting an altered structure of the cleaved protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189499 TI - [Physical basis for the application of ferromagnetics introduced into body]. AB - The review deals with some medico-biological problems of ferromagnetics applications with the use of physical fields effect (permanent and alternating magnetic fields, high frequency and laser radiation). The main aspects are the following: magnetic fluid as roentgenocontrast, substances; magnetically controlled drug delivery systems; magnetic microspheres with immobilized antibodies; thermo-magnetic cancer surgery; magnetic particles as a tool for subcellular structure investigation; magnetic particles distribution and removal from the organism. PMID- 2189500 TI - [An evaluation in the Ames test of the mutagenicity of the sewage and industrial effluents from the Baikal Paper and Pulp Combine]. AB - The use of the Ames test for the analysis of industrial effluents from cellulose production and sewage waters varying in the degree of purification with the aid of a metabolic activation system from rat and fish liver with Salmonella strains TA 98 and TA 100 revealed a strong direct mutagenic effect of strain TA 100 in samples after cellulose chlorination. The multistage procedure of sewage water purification allows to remove practically completely the mutagenic substances. A simultaneous study of cytotoxic effects of industrial effluents on mammalian cells shows that the mutagenic activity is exhibited in not toxic concentrations. The urgency of a regular biological control over the genotoxicity of industrial effluents from the sulfate production of cellulose is under discussion. PMID- 2189501 TI - [The breakdown of phthalic acid esters by microorganisms]. AB - The distribution in environment of phthalic acid esters classified according to their inherent toxicity, teratogenic, mutagenic properties and cancerogenic activity into a group of priority pollutants of biosphere is described in this review. The role of microbial community in degradation of phthalate esters has been demonstrated. The effect of such environmental factors as pH of the medium, temperature, humidity, concentration of organic matter, the introduction of promising microbial strains in natural biocenoses has been examined. The pathways of phthalate ester metabolism have been analysed in representatives of active bacterial destructors belonging to genera Nocardia, Pseudomonas and Micrococcus. The decomposition rate of phthalate esters has been shown to be correlated with structure, concentration and culture conditions. PMID- 2189502 TI - Demonstration of a nonsteroidal factor in human follicular fluid that attenuates the self-priming action of gonadotropin-releasing hormone on pituitary gonadotropes. AB - The self-priming effect of gonadotropin-releasing hormone (GnRH) on luteinizing hormone (LH) release can be demonstrated in vitro by perfusing pituitary tissue with a continuous GnRH stimulus. A characteristic biphasic response is produced. We have used this system to investigate whether or not human follicular fluid (hFF) contains a nonsteroidal substance that can attenuate the GnRH-induced LH secretion in perfused rat pituitary glands. Steroid-extracted hFF, added to the perfusing medium, attenuated the self-priming action of GnRH in a dose-dependent manner. This was not abolished by selectively depleting the inhibin content of hFF by 97% on an immunoaffinity column. Furthermore, the biological activity of the substance was resistant to heating and was removed by dialysis. It is concluded that hFF contains a nonsteroidal factor, distinct from inhibin, that can attenuate the self-priming action of GnRH on pituitary gonadotropes. PMID- 2189503 TI - Presence of amino acids and insulin in a chemically defined medium improves development of 8-cell rat embryos in vitro and subsequent implantation in vivo. AB - This study examined the effects of some components in a chemically defined medium on rat 8-cell embryo development in vitro. The basal medium was a modified culture medium for in vitro fertilization of rat oocytes, containing inorganic salts and energy substrates. After 36 h in culture, 28.8% of the 8-cell embryos developed into blastocysts in the basal medium. This percentage was increased by supplementing the basal medium with free amino acids, but not a premix of insulin/transferrin/selenium (ITS). However, ITS synergized the beneficial effect of amino acids. The beneficial effect of free amino acids could not be duplicated by bovine serum albumin. The synergistic action of ITS was primarily due to insulin. The removal of glucose and/or phosphate from the culture medium had no effect on embryo development in vitro. After transfer to unilaterally pregnant rats, 23.1% of the blastocysts formed in the basal medium developed to Day 18 fetuses, compared to 64.3% for those formed in the medium containing amino acids. These data indicate that the presence of amino acids in the culture medium is beneficial for embryo development in vitro and for implantation and fetal development following transfer to pregnant recipients. PMID- 2189504 TI - Maturity at collection and the developmental potential of rhesus monkey oocytes. AB - The purpose of this study was to evaluate the in vitro fertilizability of rhesus monkey oocytes and the developmental capacity of the resulting embryos as they relate to oocyte maturation at the time of follicular aspiration. Animals were hyperstimulated with human follicle-stimulating hormone (hFSH) and human luteinizing hormone (hLH), with follicular aspiration performed 27 h after administration of an ovulatory stimulus (1000 IU human chorionic gonadotropin [hCG] or 3 x 100 micrograms gonadotropin-releasing hormone [GnRH]). In 7 animals exhibiting a continuously rising pattern of serum estradiol through Day 10 of hyperstimulation, 45 germinal vesicle-intact (GV), 106 metaphase I (MI), and 24 metaphase II (MII) oocytes were collected and cultured in vitro. Upon reaching MII, oocytes were inseminated with 5 x 10(4) motile sperm/ml. Twenty-four percent of GV oocytes cultured in vitro matured to MII with 11 inseminated and none fertilized. Seventy-three percent of MI oocytes matured to MII in vitro with 50% inseminated and 32% fertilized. Oocytes collected at MII stage and inseminated underwent fertilization at a high rate of efficiency (93%). Pronuclear to 8-cell stage embryos were frozen and, upon thawing, 67% (10/15) survived with all blastomeres intact. Frozen-thawed embryos (2- to 6-cell) were transferred to the oviducts of 4 recipients (2 embryos/recipient) during the early luteal phase (1-3 days post LH surge) of natural menstrual cycles. Three twin pregnancies resulted. Thus, a positive correlation exists between the degree of nuclear maturation of rhesus monkey oocytes at collection and their potential for fertilization in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189505 TI - Interleukin-7 is a growth factor of precursor B and T acute lymphoblastic leukemia. AB - We investigated the proliferation-inducing effects of human recombinant interleukin-7 (IL-7) on acute lymphoblastic leukemia (ALL) cells. It is shown that IL-7 stimulates DNA synthesis in ALL cells of B-cell precursor (n = 5) as well as immature T-cell origin (n = 2). Cytogenetic analysis of the cells of four patients proliferating in IL7-supplemented cultures established the leukemic descendence of the IL-7-responsive cells. 125I-IL-7 binding experiments with the cells of one patient and with two ALL cell lines showed the presence of two types of IL-7 receptors: one with a high affinity (kd 29 to 51 pmol/L) and one with a low affinity (kd 2.3 to 76 nmol/L) for the ligand. We conclude that IL-7 is one of the cytokines involved in the complex regulation of ALL cell proliferation. PMID- 2189506 TI - Early deaths and anti-hemorrhagic treatments in acute promyelocytic leukemia. A GIMEMA retrospective study in 268 consecutive patients. AB - The records of 268 consecutive patients with acute hypergranular promyelocytic leukemia, treated at 29 Italian centers between January 1984 and December 1987, have been reviewed to assess the incidence of early hemorrhagic deaths and the effectiveness of various antihemorrhagic treatments. Three separate groups were considered: 94 patients were treated with heparin, 67 with anti-fibrinolytics (tranexamic acid, epsilon-aminocaproic acid, or aprotinin), and 107 with supportive therapy alone. The overall incidence of early hemorrhagic death (within the first 10 days of treatment) was 9.4%, with no significant differences between the various groups. Similarly, there were no differences in complete remission rates or duration of survival. The consumption of packed red blood cells and platelet concentrates was similar for two of the groups, and there was a significantly greater use of platelet concentrates for heparin-treated patients. High blast cell counts on the day of admission were significantly associated with hemorrhagic death within the first 10 days. These counts, plus high blast cell counts and low platelet counts, were associated with death within 24 hours. PMID- 2189507 TI - Western blot identification of platelet proteins that bind normal serum immunoglobulins. Characteristics of a 95-Kd reactive protein. AB - We have found that Western blots (WBs) of whole platelets exposed to normal autologous or homologous sera commonly have bands at 90 to 95 (95) Kd, and less often at 100 to 110, 80 to 85, 60 to 75, and 50 to 60 Kd when developed with antiglobulins. The percentages of normal sera producing a 95-Kd band with anti immunoglobulin G (IgG), -IgA, and -IgM are 85, 50, and 30, respectively. Antiglobulin reagents alone also produce background bands on WBs that we have shown correspond to levels of platelet-associated Igs (PAIgs) or their derivatives. Titers of 95 Kd-reactive IgG in normal sera range from 10 to 1,280 (85% less than or equal to 50), and the reaction appears to be partially F(ab')2 mediated. The 95-Kd protein is internal and differs in many respects from surface glycoproteins IIIa, IV, and V of similar apparent molecular weight. In thrombocytopenic patients there was no correlation between severity of thrombocytopenia or PAIgG of platelet eluates and corresponding serum titers of 95 Kd-reactive IgG. Some WB reactions previously reported as evidence of autoimmunity may represent normal variations in reactions of Igs with internal platelet proteins. These reactions may be immunospecific or analogous to nonspecific, partially F(ab')2-dependent binding of Igs by certain bacterial proteins. PMID- 2189508 TI - Anti-leukemia potential of interleukin-2 activated natural killer cells after bone marrow transplantation for chronic myelogenous leukemia. AB - The anti-leukemia potential of natural killer (NK) cells has been evaluated in 40 patients transplanted for chronic myelogenous leukemia (CML) to determine whether differences in NK cell function were correlated with subsequent leukemic relapse. Cells from patients and their donors were tested in 51Cr release assays against fully allogeneic CML targets and against cultured K562 targets; cells from 26 patients were tested against host-derived CML targets that were cryopreserved before transplantation. Cultured CML targets (K562) were highly susceptible to lysis by freshly isolated peripheral blood lymphocytes (PBL) and to a greater degree by PBL cultured in medium containing interleukin-2 (IL-2) in all assays performed. In contrast, noncultured CML targets were lysed only by IL-2-activated cells from a subset of patients. When present, lytic activity to CML targets was detectable as early as 3 weeks after bone marrow transplantation, and remained positive throughout the posttransplant period. Optimal lytic activity developed within the first week of culture and required greater than or equal to 250 U/mL of IL-2 in the culture medium. Lytic activity to fully allogeneic and host derived CML targets appeared to be mediated by CD16+ and CD56+ cells but not by CD3+ cells. Lysis of allogeneic CML targets was variable, but patients could be divided into two groups: those with and those without lytic activity to the majority of targets tested. The basis for the differences in lytic activity could not be ascribed to target susceptibility to lysis, the proportion of NK cells in the cultures, or to the phenotype of the NK cell subsets in the cultures. When tested in parallel, the lytic activity of donor and recipient cultures against host-derived CML targets was highly correlated, suggesting that there may be inherent differences in the ability of NK cells to recognize CML targets. The risk of relapse for patients who failed to generate lytic activity against host derived CML targets was significantly increased over that for patients with lytic activity against host leukemia. These data indicate that posttransplant immunotherapy with IL-2 designed to activate NK cells will likely augment the graft-versus-leukemia potential of the graft. PMID- 2189510 TI - Alcoholism and the dentist. PMID- 2189509 TI - Specificity of anti-neutrophil cytoplasmic autoantibodies for proteinase 3. PMID- 2189511 TI - Withdrawal symptoms and alcohol dependence: fruitful mysteries. AB - Five types of question are posed around withdrawal symptoms. (1) The reasons for the fluctuations over time in medical awareness of alcohol's capability to produce withdrawal symptoms. (2) What type of drinking schedules instigate withdrawal experience? (3) Do withdrawal phenomena get worse over time? (4) The 'addiction memory' question; and lastly (5) Is withdrawal a reinforcer for drinking behaviour? These issues point to a need for a renascence in the kind of research which is based on clinical observation and on listening to what patients have to tell, with such lines of work brought into much closer contact than before with corresponding laboratory investigation. PMID- 2189512 TI - Trends in alcohol consumption in Spain, Portugal, France and Italy from the 1950s until the 1980s. AB - This paper compares trends in alcohol consumption in Spain, Portugal, France and Italy starting from the beginning of the 1950's and extending until the 1980's and examines the modernization and internationalization of beverage preferences in these countries. The total consumption of alcohol has declined in Spain, France and Italy and the consumption of wine has shown a declining trend in all the countries studied. The traditional beverage, wine, has in Spain, Portugal and Italy been substituted by a new beverage with lower alcohol content, beer. In France the decline in wine consumption has not been substituted by the use of other alcoholic beverages. No noticeable internationalization in beverage preferences has taken place in Spain, Portugal or Italy, whereas imported beverages have gained some ground in France. PMID- 2189513 TI - Meningococcal meningitis. PMID- 2189514 TI - Congenital virus infections. PMID- 2189515 TI - Women who sexually abuse children. PMID- 2189517 TI - Experiences of a battalion medical officer in the retreat to Dunkirk: I. PMID- 2189516 TI - Falciparum malaria resistant to quinine and pyrimethamine-sulfadoxine successfully treated with mefloquine. PMID- 2189518 TI - Immunosuppressive agents in current use. AB - The use of immunosuppressants has increased as clinical applications for such therapy have become more widespread. Immunosuppressive therapy is now particularly relevant in the field of organ transplantation, a practice that has only developed over the last 20 years. Drugs used as immunosuppressants are discussed in relation to disease category, where they are of value, mode of action, and potential side effects. Future prospects concerning the development and use of immunosuppressants are considered. PMID- 2189519 TI - Current management of infantile hypertrophic pyloric stenosis. AB - Infantile hypertrophic pyloric stenosis is a relatively common paediatric condition effectively cured by Ramstedt's pyloromyotomy. Nevertheless, published results demonstrate a residual perioperative morbidity indicating a need for improved management. While technological advances in diagnosis and treatment may contribute to this, attention to the details of perioperative care coupled with a meticulous surgical approach are likely to have a much greater impact. PMID- 2189520 TI - Management of obsessive-compulsive disorder. AB - Obsessive-compulsive disorder is an anxiety disorder characterized by compulsive rituals such as excessive washing and repeated checking and phobic avoidance. The treatment of choice is behavioural psychotherapy, namely exposure and response prevention. PMID- 2189521 TI - Salmonella lung abscess causing rupture of the thoracic aorta. PMID- 2189522 TI - Pre-eclampsia: its anaesthetic implications. PMID- 2189523 TI - Surgical topic 1. Screening for surgical diseases. PMID- 2189524 TI - From categories to contexts: a decade of the 'new cross-cultural psychiatry'. AB - Over the last ten years a new approach to psychiatric knowledge has developed under the influence of social anthropology. Its origins, assumptions, methods, achievements, and limitations are reviewed. PMID- 2189525 TI - Past and revised risk estimates for cancer induced by irradiation and their influence on dose limits. PMID- 2189526 TI - Ultrasound evaluation of ectopic pregnancy including correlation with human chorionic gonadotrophin levels. AB - A total of 267 patients referred for ultrasound examination because of clinical suspicion of ectopic pregnancy were studied prospectively. The outcome was correlated with the ultrasound findings and human chorionic gonadotrophin levels using a quantitative serum assay. The value of the following in the diagnosis of ectopic pregnancy are assessed: ultrasound criteria for early diagnosis of intrauterine pregnancy before visualization of a viable fetus, the discriminatory zone of hCG and extrauterine abnormalities. PMID- 2189527 TI - Does scrotal ultrasound reduce the need for orchidectomy in the clinically malignant testis? AB - Many recent studies have confirmed the ability of ultrasound to elucidate scrotal pathology, but its place in the work-up of specific testicular problems is not yet fully defined. We investigated 15 cases where a firm clinical diagnosis of testicular malignancy was made. All cases progressed to orchidectomy. Scrotal ultrasound refuted the diagnosis of malignancy in seven cases with subsequent histological proof of benignity. However, the nature and extent of the benign disease was such that, on review, orchidectomy was considered to be the most appropriate method of treating the patient. We contend that in the case of firm clinical diagnosis of testicular malignancy, an ultrasound diagnosis of benignity will not alter management, and it is therefore not an essential part of the work up in this group of patients. PMID- 2189528 TI - A diaphragmatic nick. PMID- 2189529 TI - Final Report of the BIR fractionation study. PMID- 2189530 TI - The California Bridge--truly conservative fixed bridgework. PMID- 2189531 TI - Common acanthotic and keratotic lesions of the oral mucosa: a review. AB - White lesions of the oral mucosa are common. Dentists must be aware of the diseases that can cause these lesions, the terminology used to describe them histologically, and their significance to the patient. This paper represents a review of basic terminology and a brief description of common acanthotic and/or keratotic lesions of the oral mucous membranes. PMID- 2189532 TI - Clinical applications of osseointegrated implants. AB - In the described seven case reports, the authors have demonstrated a number of varied applications of osseointegrated implant techniques including both removable and fixed prostheses. All patients had expressed dissatisfaction with previous prosthetic efforts to restore a satisfactory level of mastication or a desire to do away with removable oral prostheses. A high level of patient satisfaction was achieved through the application of implant techniques in these patients. Proper treatment planning must now include a consideration of implant dentistry as well as the previously available conventional alternatives for our edentulous and partially edentulous patients. PMID- 2189533 TI - Localized juvenile periodontitis: a case analysis and rational approach to treatment. AB - This case involves a 14-year-old female patient affected with localized juvenile periodontitis. Treatment consisted of periodontal flap surgery in conjunction with tetracycline therapy. A successful result was obtained and maintained. The case depicts the fact that in many instances localized juvenile periodontitis can be treated with confidence and a high degree of predictability. It should also be noted that, like all treatment modalities, the treatment of this disease as discussed in this case is not the panacea and will undergo considerable changes in the future; however, in light of current knowledge, this combined treatment approach appears to be effective in LJP patients. PMID- 2189534 TI - The role of intrinsic musculature in the formation of inferior calcaneal exostoses. AB - Review of the anatomy contributing to calcaneal spur formation is provided. Freshly amputated limbs, used because they are not subject to the effects of the preservatives that effect cadaveric limbs, are the basis for the study the authors report. An alternative theory to the cause of heel spurs is presented based on that study. PMID- 2189535 TI - The heel in systemic disease. AB - Heel pain is most commonly the result of mechanical abnormality in foot structure or function. Systemic disease, however, may also affect the heel, resulting in pain, deformity, or both of the rearfoot. This article discusses and reviews notable systemic conditions, exclusive of the seronegative spondyloarthropathies, which may produce subjective or objective heel findings. Specific conditions discussed are rheumatoid arthritis, crystal deposition arthropathies, osteoporosis, diffuse idiopathic skeletal hyperostosis, diabetes mellitus, hypertrophic osteoarthropathy, Paget's disease, hyperlipidemia, sarcoidosis, sickle cell anemia, and acromegaly and their effects on the heel. PMID- 2189536 TI - History and mechanical control of heel spur pain. AB - The symptom of heel pain from heel spur syndrome has both a cause (abnormal pronation) and an effect (inflammation at the heel spur area). I believe that heel spur syndrome cause and effect can best be treated mechanically by a two stage approach. This two-stage approach uses a different orthotic for each stage. The first stage is to prescribe an orthotic to alleviate the cause through control of abnormal pronation by posting or wedging, and also to alleviate the effect by local accommodation and shock absorption of the inflamed area. The second stage of mechanical treatment is begun after the effect (local inflammation) has subsided. This second stage consists of treatment with a rigid functional orthotic to treat only the cause. This orthotic is more durable and controlling and will therefore maintain the patient and prevent abnormal pronation from occurring. Thus, the cause of pain at the heel spur area will be eliminated. Orthotics can be a great adjunct to treatment of heel spur syndrome. But, as is the case with any other method you use to treat your patients, orthotics are only as good as the theories on which you base them. There are a variety of excellent materials and computerized methods being used today for fabrication of orthotic devices, but they are only as effective as the knowledge on which you base them. If you do not understand the etiology of the mechanical problem and do not observe what treatment is successful and the reasons behind this success, the orthotic you prescribe is not going to have a high level of success, regardless of new materials or technology. You will be like the laboratory technician who can fabricate an orthotic, but cannot predict, with any level of confidence, whether it will alleviate the mechanical problem. PMID- 2189537 TI - Inferior heel spur surgery. AB - In most instances, pure mechanical heel spur surgery can and should be avoided. The proper diagnosis is extremely important because many different disorders can cause inferior heel pain like that of a mechanical cause. Described throughout the literature are many surgical approaches and techniques for this problem. Personal preference and experience dictates the choice. In some isolated cases, a specifically designed procedure may be necessary. Postoperative care is as important as the surgical procedure itself because recovery usually takes quite a long time. PMID- 2189538 TI - Neuromas of the heel. AB - Often overlooked in the differential diagnosis of heel pain is neuroma of the medial calcaneal branch of the posterior tibial nerve. Heel neuroma is an important disorder of the foot that has been misdiagnosed by physicians since the early 1900s as heel spur syndrome. The authors show how heel pain rarely has anything to do with calcaneal exostosis, but instead could be related to heel neuroma. PMID- 2189539 TI - Trauma to the heel. AB - Anatomy and soft-tissue structure are reviewed as the basis for presenting descriptions of various types of trauma. Included are discussions of puncture wounds, tendon disruptions, fractures, degloving injuries, and fascial disruptions. PMID- 2189540 TI - Tumors of the heel. AB - We have attempted to show a correlation between heel pain and tumors and tumor like conditions. The anatomy and size of the calcaneus predisposes it to increased incidence of trauma. Furthermore, the increased vascularity of the heel versus other areas of the foot may contribute to a higher incidence of both local and metastatic tumors. Most tumors and tumor-like conditions initially present with pain as the patient's primary complaint. Therefore, any complaint of heel pain must be thoroughly evaluated and treated. Accordingly, when biopsy or excision is necessary, the surgeon must plan his approach while considering the unique position and anatomic properties of the calcaneus. PMID- 2189541 TI - Diagnostic radiographic imaging of the adult calcaneus. AB - This article provides a broad overview of plain-film radiographic imaging of the adult calcaneus, with emphasis placed on the standard lateral pedal study. A general approach is offered, and the more common pathologies are reviewed. A brief review of normal CT Scan anatomy is provided. PMID- 2189542 TI - Seronegative arthritis as a cause of heel pain. AB - Seronegative disease as a cause of heel pain is not nearly as common as mechanically induced heel pain. Recognizing the clinical findings, however, will help in distinguishing this from more common forms of heel pain. PMID- 2189543 TI - Shock absorption. AB - Abnormal shock is a major cause of chronic and overuse injuries to all aspects of the lower extremity. The two major causes of abnormal shock are (1) decreased fat pad under the calcaneus and (2) dysfunction of the subtalar joint pronation mechanism during contact. Enough literature now exists to indicate that podiatrists should provide prophylactic therapy for patients that exhibit abnormal shock during contact before symptomatology in the lower extremity or spine exhibits itself. PMID- 2189544 TI - Effect of combined androgen blockade with an LHRH agonist and flutamide in one severe case of male exhibitionism. AB - A severe exhibitionist has been treated with the combination of an LHRH agonist and the antiandrogen flutamide in order to maximize androgen blocking and to control his severe deviant behaviour. The results obtained show that the androgen blockade ended his exhibitionistic behaviour and markedly decreased his sexual fantasies and activities, especially masturbation, without significant side effects. PMID- 2189545 TI - Neuroimaging and affective disorder in late life: a review. AB - Within the past two decades brain imaging techniques have given the clinician access to new anatomical and functional findings for dealing with affective disorder in the older age group. Despite the proliferation of such technology, the significance of findings on computerized axial tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) remains unclear in this patient group. The literature covering old age depression and imaging techniques is reviewed, and problems related to methodology, sample selection, and implications for the direction of future research are discussed. Current evidence particularly suggests that subcortical atrophy may be an important factor in the genesis of affective disorder in old age. The question of cognitive decline in the setting of affective disorder is examined. The use of brain imaging techniques may have particular bearing upon identification of etiology of affective disorder, prediction of treatment response, or risk of relapse. PMID- 2189546 TI - Repair processes in the treatment and induction of cancer with radiation. PMID- 2189547 TI - Cytogenetics of tumor progression. PMID- 2189548 TI - The Philadelphia chromosome translocation. A paradigm for understanding leukemia. PMID- 2189549 TI - The colony stimulating factors. Discovery, development, and clinical applications. PMID- 2189550 TI - The control of growth and differentiation in normal and leukemic blood cells. AB - The establishment of a cell culture system for the clonal development of hematopoietic cells has made it possible to discover the proteins that control growth and differentiation of different hematopoietic cell lineages and the molecular basis of normal and abnormal cell development in blood-forming tissues. A model system with myeloid cells has shown that normal hematopoietic cells require different proteins to induce cell multiplication and cell differentiation, and that a cascade of interactions between proteins determines the correct balance between immature and mature cells in normal development. Gene cloning has shown that there is a family of different genes for these proteins. Normal protein regulators of hematopoiesis can control the abnormal growth of certain types of leukemic cells and suppress malignancy by inducing differentiation to mature nondividing cells. Genetic abnormalities that give rise to malignancy in these leukemic cells can be bypassed and their effects nullified by inducing differentiation, which stops cells from multiplying. These hematopoietic regulatory proteins are active in culture and in vivo and have been used clinically to correct defects in blood cell development. The results provide new approaches to therapy. PMID- 2189551 TI - A phase III trial on the therapy of advanced pancreatic carcinoma. Evaluations of the Mallinson regimen and combined 5-fluorouracil, doxorubicin, and cisplatin. AB - One hundred eighty-seven patients with histologically proven advanced pancreatic adenocarcinoma were randomly assigned to therapy with 5-fluorouracil (5-FU) alone, to the Mallinson regimen (combined and sequential 5-FU, cyclophosphamide, methotrexate, vincristine, and mitomycin C), or to combined 5-FU, doxorubicin, and cisplatin (FAP). Patients with both measurable and nonmeasurable disease were included and the primary study end point was survival. Among 41 patients with measurable disease, objective response rates were 7% for 5-FU alone, 21% for the Mallinson regimen, and 15% for FAP. The median interval to progression for each of the three regimens was 2.5 months. Survival curves intertwined with the median survival times for 5-FU alone and the Mallinson regimen at 4.5 months and for FAP at 3.5 months. Compared with 5-FU alone, both the Mallinson regimen and FAP produced significantly more toxicity. Neither the Mallinson regimen nor FAP can be recommended as therapy for advanced pancreatic carcinoma. Any chemotherapy for this disease should remain an experimental endeavor. PMID- 2189552 TI - Synthesis and 2D-n.m.r. analysis of a pentasaccharide glycoside of the biological repeating units of Shigella flexneri variant Y polysaccharide and the preparation of a synthetic antigen. PMID- 2189553 TI - The structure of Escherichia coli K31 antigen. AB - The capsular polysaccharide of Escherichia coli K31 has been found by methylation analysis and n.m.r. spectroscopy to be based on the hexasaccharide shown. The sequence of the repeating unit was deduced from the combined results of beta elimination, lithium-ethylenediamine degradation, and hydrogen-fluoride and selective hydrolyses. The nature of the anomeric linkages, established by chromic acid oxidation, was confirmed by 1H-coupled 13C-n.m.r. spectroscopy. Two dimensional n.m.r. studies on a low molecular weight polymer obtained by bacteriophage depolymerization are also reported. (formula; see text) PMID- 2189554 TI - Structure of the K16 antigen from Escherichia coli O7:K16:H-, a Kdo-containing capsular polysaccharide. AB - The K16-antigen from E. coli Rk 21510 (O7:K16:H-) is shown to consist of the repeating unit ----2)-beta-D-Ribf-(1----3)-beta-D-Ribf-(1----5)-alpha-Kd op-(2--- of which approximately 33% is O-acetylated at position 3 of the 2-linked ribose. PMID- 2189555 TI - Principles and physics of Doppler. AB - This article reviews the available Doppler instrumentation and application to assessment of blood flow velocity. A review of the basis of quantitative measurements such as volume flow, modified Bernoulli and continuity equations, and pressure half-time are discussed. A brief technical description of Doppler color-flow mapping is presented with reference to data acquisition and display. PMID- 2189556 TI - Doppler echocardiographic quantitation of volumetric flow rate. AB - Doppler echocardiographic determination of cardiac output has been well validated in clinical and experimental settings. Doppler measurement of volumetric flow rate remains useful in clinical practice in a wide variety of settings, especially when serial or comparative determinations are required. As improved echocardiographic equipment enhances image resolution and includes more sophisticated on-line analysis packages, the feasibility of expediently quantitating flow with Doppler echocardiography will be facilitated. PMID- 2189557 TI - Doppler echocardiographic evaluation of aortic stenosis. AB - Doppler echocardiography allows accurate noninvasive measurement of transaortic velocity and pressure gradient in patients with valvular aortic stenosis. Because pressure gradients vary with transaortic volume flow, calculation of aortic valve area with the continuity equation is essential for complete echocardiographic evaluation of adult patients. The physician and sonographer should be aware of potential technical and physiologic pitfalls in applying Doppler echocardiographic techniques to the evaluation of the adult with aortic stenosis. With proper training and experience, however, the needed data can be obtained reliably and reproducibly. Doppler evaluation of patients with aortic stenosis has improved our understanding of the prevalence and natural history of this disease. In addition, Doppler measures of stenosis severity can be used in a cost effective manner for clinical decision making regarding the need for valve replacement in symptomatic adults. It now has supplanted the need for invasive measures of stenosis severity in many of these patients. PMID- 2189558 TI - Echocardiographic and Doppler studies in hypertrophic cardiomyopathy. AB - This article discusses the central role of cardiac ultrasonography-- two dimensional echocardiography, Doppler echocardiography, continuous-wave Doppler, pulsed-wave Doppler--in the clinical assessment and management of patients with hypertrophic cardiomyopathy. PMID- 2189559 TI - Doppler echocardiographic evaluation of mitral stenosis. AB - In mitral stenosis, both the pressure gradient and the valve area can be obtained noninvasively, and the effects of changes in heart rate with exercise and of medications on the pressure gradient can be readily assessed. When the appearance of the valve, the subvalvular apparatus, and chamber sizes obtained with imaging and the assessment of associated regurgitations and pulmonary hypertension by Doppler are added, this becomes a powerful tool for assessment of patients with mitral stenosis. On follow-up studies, disease progression and complications, as well as the effect of medical and surgical interventions, can be monitored. PMID- 2189560 TI - Doppler echocardiographic evaluation of aortic regurgitation. AB - Aortic regurgitation is diverse in presentation, perhaps pursuing a long indolent course or presenting as a catastrophic acute illness. Aortic regurgitation of any degree may be difficult to detect clinically, but echocardiographic Doppler studies afford a sensitive means of detecting and quantifying the lesion noninvasively. Pulsed-wave, continuous-wave, and color-flow Doppler modalities are complementary in the evaluation of aortic regurgitation, and all should be utilized in individual patients when surgery is contemplated. M-mode echocardiography and two-dimensional echocardiography have endured as excellent noninvasive means for evaluating the adequacy of ventricular hypertrophy in response to the insufficiency lesion. Recent interest in wall stress analysis may allow an index of ventricular performance that lends quantitative support for decisions to intervene surgically. Newer surgical options such as aortic valve homografts and pulmonary autografts may make surgery more attractive for patients considered for aortic valve replacement. PMID- 2189561 TI - Doppler echocardiographic evaluation of mitral regurgitation. AB - Evaluation of the severity and hemodynamic significance of mitral regurgitation remains an important and difficult problem. Cardiac ultrasound has emerged as the procedure of choice for the initial evaluation of mitral incompetence, as a result of its ability to confirm the diagnosis and provide a semiquantitative estimate of the severity of incompetence, determine its etiology, and assess the hemodynamic impact of the incompetence on ventricular function. This article reviews established as well as investigational methods of evaluating mitral incompetence by echocardiography and explores established and potential clinical applications of this evolving technology. PMID- 2189562 TI - Pulmonary artery pressure estimation by Doppler and two-dimensional echocardiography. AB - When properly executed, Doppler is a powerful and reliable means of assessing right-heart hemodynamics. Because the Doppler technique depends on ubiquitous functional regurgitant jets, it can confer the benefits of catheterization on the majority of patients having cardiac ultrasound examinations. Progress in ultrasound contrast agents may augment the accuracy of these measurements and enable determination of left-heart hemodynamics. PMID- 2189563 TI - Echo-Doppler and color-flow imaging in congenital heart disease. AB - Enormous strides in diagnosis and management have allowed many patients with congenital heart disease to reach adulthood. Proper care of these individuals requires knowledge of the anatomic and hemodynamic faults of the original defect, the dynamic changes that occur with time, and the effects of adult diseases or surgical intervention on that physiology. Echocardiographic and Doppler assessment of these patients has revolutionized their management. This article has discussed individual abnormalities such as shunts, obstructive or regurgitant lesions, and great-vessel and chamber malpositions, as well as selective aspects of more complex malformations. In the patient with congenital heart disease, whether unoperated or postoperative, a complete echo-Doppler examination includes complete anatomic delineation of intra- and extracardiac structures using combined two-dimensional and color-flow imaging, assessment of chamber sizes and myocardial function, and complementary pulsed and continuous-wave Doppler and color-flow imaging to search for and quantitate valvular, subvalvular or supravalvular stenosis or regurgitation; extra- and intracardiac conduit stenosis; pulmonary and systemic venous obstruction; transseptal or patch shunts; and intracardiac hemodynamics. PMID- 2189564 TI - Evaluation of left ventricular diastolic function. AB - Doppler echocardiography can provide insight into the diastolic properties of the left ventricle. The hemodynamic origins of the diastolic mitral flow velocity profile are reviewed and Doppler information is compared to other measures of left ventricular diastolic function. Factors affecting the mitral diastolic flow velocity in both normal populations and pathologic conditions are discussed and the reported normal indexes of diastolic transmitral velocity are criticized. PMID- 2189565 TI - Doppler echocardiography in pericardial disease. AB - In conclusion, an understanding of the physiology of cardiac tamponade and pericardial constriction allows accurate interpretation of the changes in SVC and transatrioventricular valve Doppler flow velocities that characterize each abnormality. Meticulous attention to detail in obtaining the studies is essential for accurate diagnosis, because relative changes in flow velocities during respiration may be obscured or misinterpreted if poor-quality data are obtained. In our laboratory, SVC Doppler studies have proved to be the most technically feasible in patients with cardiac tamponade, but transvalvular studies provide important complementary data and are critical in constrictive pericarditis. Hepatic vein Doppler offers an alternative approach to the analysis of systemic venous return, particularly in stable patients with dilated hepatic veins. These studies must always be interpreted with attention to possible confounding variables such as previous pericardiotomy, significant tricuspid regurgitation, severe chronic lung disease, or restrictive cardiomyopathy. As physiologic rather than anatomic indicators, they are a valuable addition to echocardiography in assessing the hemodynamic significance of pericardial abnormalities. PMID- 2189566 TI - Doppler echocardiography in dilated and restrictive cardiomyopathies. AB - Dilated cardiomyopathy is characterized by systolic dysfunction and cardiac enlargement of unknown origin. Various Doppler modalities are useful to detect and quantitate atrioventricular regurgitation, which is common and contributes to clinical symptoms. Pulsed Doppler assessment of mitral and tricuspid inflow velocities shows a spectrum of findings indicative of abnormal diastolic function and hemodynamic status. When mitral regurgitation is more than moderate and heart failure is severe, the ratio between early inflow E wave to atrial inflow A wave peak velocities is increased. Mitral deceleration time may be short. When mitral regurgitation is trivial and left atrial pressure is not increased, abnormal relaxation may be detected as a low E:A ratio. Mitral deceleration time and isovolumic relaxation time are prolonged. In restrictive cardiomyopathy, there is an abrupt limitation in early ventricular filling due to abnormal compliance of endocardial or endomyocardial origin. Mitral and tricuspid inflow velocities show normal to increased early peak velocity, rapid deceleration time, low peak atrial velocity, and an increased E:A ratio. Differentiation between restriction and constriction might be possible by the demonstration in pericardial constriction of inspiratory decreases in mitral early inflow peak velocities and in prolongation of isovolumic relaxation time, with reciprocal changes on tricuspid inflow velocity profiles. In constriction, these respiratory variations are caused by the ventricular limitation to accommodate changes in venous return due to the pericardial shell. Doppler abnormalities and two-dimensional echocardiographic assessment of ventricular and atrial size and ejection fraction provide the practicing physician with valuable diagnostic information. PMID- 2189567 TI - Echocardiographic evaluation of prosthetic cardiac valves. AB - Comprehensive echocardiographic examination of patients with prosthetic cardiac valves using M-mode, two-dimensional, conventional, and color Doppler echocardiography represents an invaluable clinical tool in the serial follow-up of these patients. A thorough knowledge of these techniques and their limitations allows accurate assessment and prevention of misdiagnoses. PMID- 2189568 TI - Role of transesophageal echocardiography in diagnosis and management of cardiovascular disease. AB - Transesophageal echocardiography is a relatively new imaging technique that is rapidly evolving into a major tool for general cardiac imaging. This article focuses on the role of transesophageal echocardiography in the diagnosis and management of cardiovascular disease. PMID- 2189569 TI - Optimised function for determining time to peak creatine kinase and creatine kinase-MB as non-invasive reperfusion indicators after thrombolytic therapy in acute myocardial infarction. AB - STUDY OBJECTIVE: The aim of the study was to investigate the use of an optimised function to approximate and interpolate the time course of serum creatine kinase and creatine kinase-MB values after thrombolytic therapy in acute myocardial infarction. DESIGN: A three parameter interpolating function was developed which approximates the time course of serum enzyme levels. In the proposed function, time to peak creatine kinase and maximum of creatine kinase determined from raw data were used as starting parameters of the non-linear interpolation routine, thus providing ideal starting conditions for the iteration. The efficacy of the function was compared with that of three other functions cited in published reports (log-normal distribution function, modified gamma density function, three compartment function). SUBJECTS: Serum enzyme data from 20 patients with acute myocardial infarction were used in the comparisons. The patients have all been treated with anisoylated plasminogen streptokinase activator complex. RESULTS: In comparison with the other models, deviations of the experimental model function from the raw data were minimal. The fit remained stable for time intervals between blood samples of up to 6 h. CONCLUSIONS - Due to its numerical stability, the function outlined in this study is suitable for large clinical reperfusion trials. In the case of uncomplicated infarctions without thrombolytic therapy, the area under the creatine kinase activity curve could be directly calculated in terms of maximum activity and time to peak. PMID- 2189570 TI - [Thyroid gland volume. Methods of its determination and their significance]. AB - For the assessment of the volume of the thyroid gland palpation, sonography or scintigraphy can be used. Palpation serves only as orientation, it underrates large goitres and a false positive diagnosis of goitre cannot be ruled out. Sonography uses a static echotomographic method or a dynamic empirical method. Echotomography is at present the most reliable method of assessment of the thyroid volume in vivo. The value of conventional scintigraphy for assessment of the thyroid volume is only historical, more accurate three-dimensional radionuclide diagnostic methods are so far not currently available in this country. PMID- 2189571 TI - [Beta-2-microglobulin and ankylosing spondylitis]. AB - Serum beta-2-microglobulin was examined by radioimmunoassay in 103 patients with ankylosing spondylitis and 111 healthy blood-donors. Statistically significant difference between the group of patients and healthy individuals was found related to increased levels of this protein in patients with ankylosing spondylitis. Furthers correlation analysis of beta-2-microglobulin in patients with ankylosing spondylitis and chosen clinical and humoral parameters of the disease activity was performed. Positive, statistically significant correlation with erythrocyte sedimentation rate, plasmatic gamma globulins, duration of morning stiffness and global activity of the disease was proved. Higher levels of beta-2-microglobulin in patients with ankylosing spondylitis could be attributed to activation of monocyte macrophages system in subpopulation of cytotoxic T lymphocytes, which might be the evidence of the involvement of cytotoxic-T cell mechanisms in the pathogenesis of this disease. PMID- 2189572 TI - [The nomination of J.K. Mikan as professor of botany at the Prague Medical School]. PMID- 2189573 TI - [A remembrance of Dr. L'udovit Markusovky , the founder of rhinology]. PMID- 2189574 TI - Outbreak of Escherichia coli O157:H7 in a nursing home--Ontario. PMID- 2189575 TI - [The concept of minimal brain dysfunction]. AB - The development of the concept of "minimal" brain dysfunctions" can be followed up in the professional literature since the forties. An important contribution was the monograph by O. Kucera et al. (1961) which emphasizes the interaction of the affected child with his social environment. In the seventies and eighties there is a trend to divide the overall concept of minimal brain dysfunctions into individual more accurately defined units comprising certain groups of symptoms (specific disorders of learning, the hyperactivity syndrome, the syndrome of impaired attention, etc.). The article emphasizes the practical usefulness of the term minimal brain dysfunctions in the communication of workers from different disciplines and the necessity to derive from it provisions for the benefit of the affected children at different levels of social practice. PMID- 2189576 TI - [The reliability of ultrasonic diagnosis in diaphragmatic rupture]. AB - The author detected a traumatic prolapse of stomach into thorax cavity. The X-ray examination was made only after ultrasonography. Two days after the operation, which confirmed the sonographic finding, symptoms of ileus became evident. The following ultrasonographic finding proved to be very similar to that made before the operation. A relapse of the prolapse was assumed to have occurred, but was not confirmed by a new operation. Since the X-ray examination of the stomach two months after the operation revealed a hiatus hernia, the author is of the opinion that a sliding hernia may have been cause of the erroneous diagnosis of the prolapse relapse. PMID- 2189577 TI - [Neurinoma of the ulnar nerve detected by ultrasonography: case report and discussion]. AB - The author describes the observation of nervus ulnaris neurinoma in a 10-year boy, who manifested the tumour clinically as a palpation -sensitive resistance. It was represented in the ultrasonographic picture as a sharply demarcated ovoid lesion of strongly hypo-echogenic character, homogenous echo-structure, while distal enhancement was mildly expressed behind the tumour. Based on the analysis of literature data the author discusses in detail ultrasonographic picture of tumours of peripheral nerves. PMID- 2189578 TI - [Development and perspectives in Czechoslovak radiology]. PMID- 2189579 TI - [Ultrasound anatomy of the liver]. AB - The authors review the modern concept of liver anatomy, related to the needs of surgeons in segmental resections. Important anatomical structures are described participating in division of the liver into four basic segments. The ultrasound anatomy of portal system, hepatic veins, hepatic fissures and liver hilus are dealt with in detail. Criteria for perfect examination of the liver by ultrasound are defined and representability of key anatomical structure under optimal conditions is analyzed in a group of 100 patients. The only non-constantly represented structure was fissura interlobaris (44%). Hepatic veins proved to be the most variable structures (17%). The results show that segmental anatomy of the liver may be very well represented by ultrasound. The authors discuss the importance of perfect knowledge of anatomy for quality examination. PMID- 2189580 TI - [The ultrasonic picture of acute appendicitis]. AB - A total of 42 patients with clinically suspect acute appendicitis or equivocal clinical finding indicating this diagnosis were examined by means of high resolution ultrasonography. The sensitivity reached in a group of 14 patients with acute appendicitis confirmed by surgery was 92.8%. The finding was considered positive if the appendix was visualized and, at the same time, its wall was wider than 3 mm or if there was an anechogenic lumen. In this way the specificity for the diagnosis reached 100%, overall accuracy reaching 95.2%. In this study there were two non-diagnostic cases and one false-negative case. In one subject without clinical signs of acute appendicitis there was a picture of normal appendix. A detailed attention was also paid to eight patients (from the total of 26 who were indeed negative), where ultrasonography contributed to the detection of another organic origin of the patients' complaints. The results have shown that ultrasonography may significantly contribute in conditions, where the surgeon is reluctant whether to operate on or not. This method appears to be a contribution also for differential diagnosis in this area. PMID- 2189581 TI - [Ultrasonography in the diagnosis of hyperparathyroidism]. AB - Ultrasonography is a direct method of representation, giving various advantages over other methods in the examination of parathyroid glands: it is rapid, non radiation and economically undemanding. Dynamic examination by means of the linear electronic transducer of 3.5 MHz and the use of water path was used in 37 patients. In 7 patients with primary hyperparathyroidism was the examination rapid and the pictures of the adenomas were persuasive. In 30 patients with secondary hyperparathyroidism were found characteristic pictures, if the glands were enlarged to 8 mm or more. For the diagnosis of smaller glands a high resolution transducer will be necessary. Histological finding was available in 21 patients undergoing operation, and easily available method and it is therefore the procedure of the first choice. PMID- 2189582 TI - Protective effect of baker's yeast mannan against Listeria monocytogenes and Pseudomonas aeruginosa infection in mice. AB - The neutral mannan (WNM) and the acidic mannan (WAM025) fractions from baker's yeast (Saccharomyces cerevisiae) were found to manifest significant protective effects against intraperitoneal and intravenous infections of Listeria monocytogenes and Pseudomonas aeruginosa in mice. A remarkable decrease in the number of microbial cells in spleen and liver was observed in mice inoculated with these microorganisms after administration of either mannan fraction. In order to clarify the mechanism of the protective effects, we investigated in vitro the bactericidal activity and lysosomal enzyme activities such as myeloperoxidase, acid phosphatase, and neutral protease, in Kupffer cells (KCs) from mice pretreated with either mannan fraction. KCs from mice administered with these mannan fractions showed an enhanced killing effect on these bacteria in vitro, and neutral protease activity was considered to be one of the important factors in the killing effect on both L. monocytogenes and P. aeruginosa. PMID- 2189583 TI - Projections of HIV infections and AIDS cases to the year 2000. AB - After the recognition of AIDS (acquired immunodeficiency syndrome) in the early 1980s, uncertainty about the present and future dimensions of HIV (human immunodeficiency virus) infection led to the development of many models to estimate current and future numbers of HIV infections and AIDS cases. The Global Programme on AIDS (GPA) of the World Health Organization (WHO) has developed an AIDS projection model which relies on available HIV seroprevalence data and on the annual rate of progression from HIV infection to AIDS for use in areas where reporting of AIDS cases is incomplete, and where scant data are available to quantify biological and human behavioural variables. Virtually all models, including the WHO model, have projected large increases in the number of AIDS cases by the early 1990s. Such short-term projections are considered relatively reliable since most of the new AIDS cases will develop in persons already infected with HIV. Longer-term prediction (10 years or longer) is less reliable because HIV prevalence and future trends are determined by many variables, most of which are still not well understood. WHO has now applied the Delphi method to project HIV prevalence from the year 1988 to mid-2000. This method attempts to improve the quality of the judgements and estimates for relatively uncertain issues by the systematic use of knowledgeable "experts". The mean value of the Delphi projections for HIV prevalence in the year 2000 is between 3 and 4 times the 1988 base estimate of 5.1 million; these projections have been used to obtain annual estimates of adult AIDS cases up to the year 2000. Coordinated HIV/AIDS prevention and control programmes are considered by the Delphi participants to be potentially capable of preventing almost half of the new HIV infections that would otherwise occur between 1988 and the year 2000. However, more than half of the approximately 5 million AIDS cases which are projected for the next decade will occur despite the most rigorous and effective HIV/AIDS prevention efforts since these AIDS cases will develop in persons whose HIV infection was acquired prior to 1989. The Delphi projections of HIV infection and AIDS cases derived from the WHO projection model need to be periodically reviewed and modified as additional data become available. These projections should be viewed as the first of many attempts to develop estimates for planning strategies to combat the HIV/AIDS pandemic in the 1990s. PMID- 2189584 TI - Diagnostic performance indices for immunofluorescent tests and enzyme immunoassays of leishmaniasis sera from northern and north-eastern Brazil. AB - A total of 341 sera were screened for anti-Leishmania IgA, IgG, and IgM antibodies by immunofluorescent (IF) tests and enzyme immunoassay (ELISA). Altogether, 292 of the sera originated from patients with clinically as well as parasitologically diagnosed (positive lesion imprint or the Montenegro skin test) cutaneous leishmaniasis; 49 of the sera were from controls from the same base population. In terms of diagnostic performance, the ELISAs for IgG and IgM yielded indices of diagnostic utility, and the positive predictive value for the IgG-ELISA was 94.6%. A remarkably high specificity (100%) was obtained with the IgA-IF test, but its sensitivity was very low. PMID- 2189585 TI - Sensitivity of Plasmodium falciparum to chloroquine and sulfadoxine/pyrimethamine in Nigerian children. AB - The in vivo sensitivity of Plasmodium falciparum to chloroquine and sulfadoxine/pyrimethamine was evaluated in children under 5 years of age in two areas of southern Nigeria in 1987. A modification of the WHO Standard Field and Extended Tests (in vivo) was used, with follow-up on days, 2, 3, 7, and 14 after treatment with 25 mg chloroquine per kg body weight given over 3 days, or with standard doses of sulfadoxine/pyrimethamine. Clinical and parasitological evaluations were performed. At Igbo Ora, in Oyo State, where by day 7 chloroquine was clinically successful in 94.4% of 36 children and sulfadoxine/pyrimethamine in 91.7% of 36 children, there were no parasitological failures in either treatment group. Fever regressed significantly more rapidly with chloroquine than with sulfadoxine/pyrimethamine. At Oban, in Cross River State, initial parasite densities decreased markedly with the chloroquine regimen but 63.6% of 44 children were parasitological failures on days 3, 7, or 14; and all of the 26 children who failed parasitologically and completed follow-up were successfully treated with sulfadoxine/pyrimethamine. By day 7, clinical success was demonstrated for 77.3% of the children treated with chloroquine. The in vitro sensitivity to chloroquine, quinine, and mefloquine at Igbo Ora indicated that isolates of P. falciparum were sensitive to chloroquine and quinine, but had reduced sensitivity to mefloquine. Because of its continued clinical efficacy, chloroquine remains the recommended treatment for children with uncomplicated malaria in Nigeria. Health providers are, however, encouraged to maintain supplies of sulfadoxine/pyrimethamine as an alternative and to refer patients promptly if necessary. PMID- 2189586 TI - Mefloquine therapy for Plasmodium falciparum malaria in children under 5 years of age in Malawi: in vivo/in vitro efficacy and correlation of drug concentration with parasitological outcome. AB - The in vivo and in vitro response of Plasmodium falciparum to a single oral dose of mefloquine (25 mg/kg body weight (M25) or 15 mg/kg (M15] was studied in children under 5 years of age in Malawi. Of the children who received mefloquine, 35% vomited at least once, and 10% did not tolerate the drug because of vomiting. The therapy failure rates for the M25 group on day 7, 14, and 28 were 15%, 18%, and 42%, respectively, and these did not differ significantly from those for the M15 group (4%, 18%, and 59%). In contrast, 34 in vitro microtests (17 per group) showed schizont inhibition at less than or equal to 32 pmol mefloquine per test well. On day 7, the concentration of mefloquine in samples of blood was significantly lower in both the M25 and M15 groups for children who were parasitaemic on day 7 than in samples from those who were aparasitaemic. A positive blood smear on day 7 was strongly associated with a mefloquine concentration of less than 500 ng/ml blood on day 2 or day 7 (P less than 0.0003). Vomiting was associated with a low mefloquine concentration on day 2 but not day 7. These results suggest that mefloquine is effective against P. falciparum in Malawi but that for young children the therapy appears to be complicated by frequent vomiting. PMID- 2189587 TI - Antibiotic susceptibility of Escherichia coli isolates from inpatients with urinary tract infections in hospitals in Addis Ababa and Stockholm. AB - A high level of antimicrobial resistance of bacteria has been detected at the Tikur Anbessa Hospital (TAH), Addis Ababa, for many years. In contrast, at the Karolinska Hospital (KH), Stockholm, the level of resistance is low. Reported are the results of an investigation of the correlation between antibiotic usage and the antimicrobial resistance rates of Escherichia coli isolates from patients with urinary tract infections in these hospitals. At TAH the strains of E. coli isolated were considerably more resistant to all seven antibiotics tested. The level of multiresistance was 63% at TAH and 7% at KH. There were no significant differences in the total amount of antibiotics used in the two hospitals, except for antituberculosis agents. The strain biotypes and antibiograms, together with the length of patients' hospitalization before a positive urine culture was obtained, suggest that the majority of the strains from TAH were of nosocomial origin. PMID- 2189588 TI - Quality control of BCG vaccine by WHO: a review of factors that may influence vaccine effectiveness and safety. AB - WHO oversees the quality control of BCG vaccine via a system that includes regular testing of products by in vitro methods and clinical trials. Three parent strains of BCG (Glaxo-1077, Tokyo-172, and Pasteur-1173P2) account for over 90% of the vaccines currently in use worldwide. Important characteristics of the vaccine preparations are summarized here, along with their physical-chemical properties. In instances where diagnostic criteria for tuberculosis are stringent, there is no evidence that when administered to newborns different preparations of BCG vaccine exhibit different efficacies; however, the incidence of BCG-associated adverse reactions does correlate with the type of preparation. Other factors, including dose, administration technique, and recipient characteristics are also important in determining vaccine-associated reactions. PMID- 2189589 TI - Hepatic tissue distribution of doxorubicin-loaded nanoparticles after i.v. administration in reticulosarcoma M 5076 metastasis-bearing mice. AB - In our previous studies, doxorubicin-loaded polyisohexylcyanoacrylate nanoparticles have been proven to increase dramatically the antitumoral activity of the cytotoxic agent in metastasis-bearing mice. The experimental model consisted of metastases induced by i.v. inoculation of reticulosarcoma M 5076 cell suspension to C57BL/6 mice. The improved efficacy of the drug was noted in terms of either metastasis count or survival. Therefore, tissue-distribution studies of this drug delivery system within the metastatic liver after i.v. administration were undertaken to gain more insight into the mechanism of action. Doxorubicin measurements in healthy hepatic or neoplastic tissue were carried out together with histological examinations using transmission electron microscopy. These results demonstrated the hepatic tissue to be an efficient reservoir of the drug when it was injected associated with nanoparticles. Accumulation of biodegradable nanoparticles with associated doxorubicin in Kupffer cells created a gradient of drug concentration for a massive and prolonged diffusion of the free drug towards the neoplastic tissue. PMID- 2189590 TI - Cephalosporins increase the renal clearance of methotrexate and 7 hydroxymethotrexate in rabbits. AB - Anaesthetized rabbits were infused with methotrexate (MTX; 30 micrograms x kg-1 x min-1) for 4 h. Constant plasma concentrations of MTX and its main metabolite 7 hydroxymethotrexate (7-OH-MTX) were achieved 40-60 min after the start of the infusion. In all, 50% of the infused MTX was eliminated by the kidney; another 15%-30% was hydroxylated and excreted as 7-OH-MTX in the urine. A concomitant infusion of penicillin G (3.96 mg x kg-1 x min-1) decreased the renal clearance of MTX and 7-OH-MTX, probably by competitive antagonism at the common tubular secretion site. In contrast, the four cephalosporins ceftriaxone, ceftazidime, ceftizoxime and cefoperazone all increased the renal clearance of MTX and 7-OH MTX. At similar plasma concentrations, ceftriaxone and ceftazidime were almost equipotent, ceftizoxime was less effective and cefoperazone seemed to have a biphasic effect, depressing the clearance of MTX and 7-OH-MTX at higher drug concentrations. The effects are best explained by an inhibition of the tubular reabsorption of the cytostatic and its metabolite. The results suggest that cephalosporins are a better choice than penicillin for antibiotic treatment during MTX therapy. PMID- 2189591 TI - Intrapleural etoposide for malignant effusion. AB - The pharmacology, toxicity, and therapeutic effectiveness of etoposide (VP-16) given by the intrapleural route were examined in a phase I trial. Ten patients with malignant pleural effusion received 100, 150, or 225 mg/m2 VP-16 infused over 2 h into the pleural space after drainage of pleural fluid. The administration of VP-16 was tolerated well, with no local pain, increase in cough, dyspnea, or infection. Myelosuppression was mild at doses of 150 mg/m2 or less but severe at 225 mg/m2. Drug levels were followed in both plasma and pleural fluid for up to 12 h. Clearance of VP-16 from the pleural cavity was low at 2 ml/min m2. Peak pleural-fluid drug levels in patients receiving 225 mg/m2 exceeded 300 micrograms/ml, whereas peak drug concentrations in corresponding plasma samples obtained at the same time amounted to less than 10 micrograms/ml. Serial chest X-rays showed no disappearance of pleural effusion in nine evaluable patients. However, follow-up investigation of pleural fluid characteristics [carcinoembryonic antigen (CEA), lactic dehydrogenase (LDH), and cytologic examination] suggested some evidence of local therapeutic benefit. PMID- 2189592 TI - High-dose carboplatin, cyclophosphamide, and BCNU with autologous bone marrow support: excessive hepatic toxicity. AB - Intensive doses of carboplatin, cyclophosphamide, and BCNU with autologous bone marrow support were given to four patients with advanced melanoma. Three developed clinically diagnosed, severe veno-occlusive liver disease, which was fatal in two cases. The dose of carboplatin (450 mg/m2) was comparable with that used in ambulatory regimens. At the doses and schedule employed, this three-drug combination produced excessive hepatic toxicity. Caution is suggested when giving carboplatin in combination with intensive doses of other chemotherapeutic agents with known hepatotoxic potential. PMID- 2189593 TI - Dose intensity of carboplatin in combination with cyclophosphamide or ifosfamide. AB - In two separate studies of patients with ovarian cancer, subjects were treated on a protocol comprising 400 mg/m2 carboplatin in combination with 1 g/m2 cyclophosphamide (group A) or 5 g/m2 ifosfamide with mesna (group B). The dose intensities achieved in group A were 87.2 mg/m2 carboplatin per week and 245.8 mg/m2 cyclophosphamide per week (34 patients). In group B, the dose intensities achieved were 124.1 mg/m2 carboplatin per week and 2,020 mg/m2 ifosfamide per week (25 patients). Two formulae for the prediction of the optimal dose of carboplatin based on renal function and degree of myelosuppression are compared with that based on surface area, and that recently proposed by Calvert is recommended. The importance of dose intensity and the total dose delivered in phase II and III studies is emphasized. PMID- 2189594 TI - Phase II study of carboplatin/ifosfamide in untreated advanced cervical cancer. AB - A total of 32 patients with advanced squamous-cell carcinoma of the cervix were treated with 300 mg/m2 i.v. carboplatin and 5 g/m2 ifosfamide as a 24-h i.v. infusion, both given on day 1 every 4 weeks. In all, 3 (9%) complete responses (CRs) and 19 (59%) objective responses (CR + PR) were achieved in 32 patients. Myelosuppression with leukopenia and/or thrombocytopenia of WHO grade 4 in 28% and 13% of patients, respectively, was the main toxicity. The results of our study suggest that carboplatin/ifosfamide is active as neoadjuvant treatment in advanced cervical cancer. PMID- 2189595 TI - Carboplatin and ifosfamide in ovarian cancer phase II and III trials. London Gynaecological Oncology Group. AB - Over the past few years controversy has continued as to whether alkylating agents such as cyclophosphamide or chlorambucil are as effective as cisplatin in advanced ovarian cancer. Arguments have also been put forward against the use of combination chemotherapy, which is clearly more toxic than single-agent treatment and is probably no more effective than a single-agent platinum compound except in terms of producing a higher response rate. Certainly survival is not improved. PMID- 2189596 TI - Do we know the cause of xeroderma pigmentosum? AB - DNA repair in mammals consists of a large family of genes that encode a variety of mutually interacting gene products. These gene products coordinately locate and prepare damaged sites in chromatin for eventual excision and replacement and interact with transcriptionally active and replicating regions. Subsets of repair genes are represented by the complementation groups of xeroderma pigmentosum (XP), Cockayne syndrome, trichothiodystrophy and the ERCC series, which overlap one another to varying degrees. Cloned DNA sequences or whole chromosomes correct the UV-sensitive phenotype of XP by only 6-50%, which may be informative for the precise mechanisms of complementation and repair and for the relative importance of various UV photoproducts. Repair deficiencies in vivo are associated with increases in the toxic effects of UV damage and chronic expression of damage inducible genes, with consequent implications for viability, development, neurological and immunological function, and carcinogenesis. PMID- 2189597 TI - The effect of menhaden oil on choline-deficiency-induced hepatic ornithine decarboxylase activity and hepatocyte insulin receptor binding. AB - The effects of menhaden oil on the choline-deficient (CD) diet tumor promotion regimen-induced alterations in hepatocyte insulin receptors and the cellular ornithine decarboxylase (ODC) activity have been investigated in this study. Male Sprague-Dawley rats exposed to the tumor-promoting regimen of a CD diet for 10 days showed increases in hepatic ODC activity from 2.68 +/- 0.42 pmol 14CO2/mg protein/h in the animals fed basal control chow (C) to 13.54 +/- 2.38 (P less than 0.02) in the rats fed CD diet. These changes in ODC occur simultaneously with the alterations in hormone receptor binding as reported previously for insulin. Replacement of the lipid present in the control diet with 15% menhaden oil (CMO) had no significant effect on ODC activity (0.91 +/- 0.21), or on the number of insulin receptors (206,000 +/- 37,000) and the Kd (7.4 +/- 1.6). Sequential treatment with 10 days of CD diet and then 10 days of the C diet, resulted in a reversal in the elevated, CD-induced hepatic ODC activity to the control levels; however, substituting 15% menhaden oil for the fat present in the CD diet (CDMO) enhanced this enzymatic activity. In contrast, both sequential and CDMO treatments prevented the insulin receptor alterations induced by the CD diet. These data demonstrate that the CD diet-induced insulin receptor alterations occur concurrently with the induction of ODC activity. But insulin receptor changes and the increased ODC activity are affected differently by CDMO treatment, suggesting that their induction by the CD diet is through distinct mechanisms and only the receptor alterations correspond with the tumor-promoting action of CD diet regimen. PMID- 2189599 TI - Quantitative relationship between mutagenic potency in the Ara test of Salmonella typhimurium and carcinogenic potency in rodents. A study of 11 direct-acting monofunctional alkylating agents. AB - This work attempted to derive a quantitative relationship between mutagenicity and carcinogenicity by examining the association between mutagenic potency in the Ara test of Salmonella typhimurium and carcinogenic potency in rodents. Mutagenesis was monitored by selecting forward mutations to L-arabinose resistance. Lethality was measured at equivalent experimental conditions to those of mutant yield by using a mixed population of a pair of isogenic strains distinguished by their differential nutritional requirements. The study was carried out with a group of 11 direct-acting monofunctional alkylating agents, which failed to show any quantitative correlation in the histidine reverse mutation test. Our data suggest that the mutagenic efficiency of the compounds is directly proportional to the magnitude of the maximum yield of L-arabinose resistance mutants and inversely proportional to the dose and the number of lethal hits at which the maximum yield occurs. A highly significant correlation (r10 = 0.86, P less than 0.01) was found between the mutagenic efficiencies of the compounds in the Ara test and their carcinogenic potencies in rodents, expressed as TD50 ('tumor dose' 50) values. The result suggests that the Ara forward-mutation test of S. typhimurium might be capable of reflecting the relative potency of animal carcinogens, at least when confined to particular chemical classes. A more generic and definitive conclusion about the predictive value of the Ara test would require this analysis to be extended to other types of genotoxic carcinogens. PMID- 2189598 TI - Effects of dietary and intraperitoneally administered beta-naphthoflavone on mutagenicity and tissue distribution of Trp-P-1 in the rat. AB - The effect of dietary beta-naphthoflavone (BNF) on tissue retention of 3-amino 1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) was studied in the rat. Female rats, 3 weeks old, were fed a BNF-containing diet for 3 days before being dosed orally or i.v. with 14C-labelled Trp-P-1. The rats were killed at 4, 24 or 48 h after dosage and subjected to tape-section autoradiography. The tissue localization of Trp-P-1-derived radioactivity was compared to that observed in untreated rats and in rats given BNF i.p. Ethoxyresorufin-O-deethylase (EROD) activity and mutagenicity of Trp-P-1 in the Ames test, using S9 prepared from forestomach, glandular stomach, small intestine, liver and lung, were used as in vitro assays to measure the degree of cytochrome P450IA1 and/or P450IA2 induction. Dietary BNF treatment caused a 30- to 40-fold increase in EROD activity in the small intestine, but only a 2-fold increase in the liver and the lung. These inter-organ differences were not observed after i.p. administration of BNF. The increase in mutagenicity of Trp-P-1 in the Ames test could be correlated to the increase in EROD activity. The autoradiographic data showed that the route of administration of BNF as well as of Trp-P-1 were important for the tissue localization of Trp-P-1. Dietary BNF treatment caused a pronounced retention of Trp-P-1-derived radioactivity in the epithelia of the small intestine, forestomach, oesophagus and the oral cavity, regardless of the administration route of Trp-P-1; a similar though less pronounced epithelial retention was observed after i.p. injection of BNF. A clear-cut boundary of accumulated radioactivity between the forestomach and the glandular stomach where the levels were almost non-detectable was observed in rats fed the BNF-containing diet. It is concluded that dietary inducers may be important determinants of metabolism and tissue distribution of toxic compounds. PMID- 2189600 TI - Therapeutic contact lenses. PMID- 2189601 TI - The effect of synthetic very low calorie diets on the GH-IGF-1 axis in obese subjects. AB - IGF-1 concentrations were measured in plasma from 20 obese patients and 20 age- and sex-matched control subjects all of whom were fasting. Plasma IGF-1 concentrations were lower (p less than 0.05) in the obese individuals than in the controls. Plasma GH and insulin responses to stimulation with oral glucose were measured in 7 healthy normal weight individuals and both before and after energy restriction in 7 obese individuals. Before treatment the obese individuals were hyperinsulinaemic (fasting and integrated stimulated concentrations p less than 0.05) and showed attenuation of the plasma GH response to stimulation (peak and integrated stimulated values p less than 0.05 and less than 0.005, respectively) following oral glucose when compared to normal weight controls. Plasma insulin levels fell (both fasting and integrated concentrations p less than 0.05 and less than 0.005, respectively) and stimulated plasma GH responses increased (both peak and integrated values p less than 0.01 and less than 0.05, respectively) in the obese individuals following 3 wk treatment with a synthetic very low energy diet. Plasma IGF-1 concentrations remained unchanged during energy restriction. These results fail to support an endocrine IGF-1 mediated feedback inhibition on the hypothalamic-pituitary axis as the cause of the attenuated release of GH in obesity. PMID- 2189603 TI - Gonadal neoplasia and abnormal sexual differentiation. PMID- 2189602 TI - Thyrotoxicosis due to pituitary resistance to thyroid hormones. Successful control with D thyroxine: a study in three patients. AB - Selective pituitary resistance to thyroid hormone (PRTH) is responsible for thyrotoxicosis due to inappropriate secretion of TSH. The TSH suppressive action of D-thyroxine (DT4) has been previously documented in euthyroid and hypothyroid subjects. This prompted us to treat with DT4 three patients with PRTH uncontrolled by anti-thyroid drugs (ATD) alone or supplemented with bromocriptine, and whose follow-up had been complicated by atrial fibrillation in two patients. Because of 100% cross-reactivity between the D and L isomers of T4 and T3 in our RIAs, thyroglobulin (Tg) was used as an index of thyroid secretion. Under ATD, TSH and Tg levels were respectively: 35 mIU/l and 670.5 pmol/l (patient 1), 87 mIU/l and 453 pmol/l (patient 2) and 110 mIU/l and 906 pmol/l (patient 3). When DT4 was added (patient 1, 3 mg daily; patients 2 and 3, 2 mg daily) to the same dose of ATD, plasma TSH and Tg levels fell but were still over the upper limit of normal and thyrotoxicosis persisted as illustrated by a recurrence of atrial fibrillation in one patient. When ATD were withdrawn and DT4 given alone (2 mg daily) all symptoms subsided within 1 month while TSH and Tg levels fell within the normal range. TSH normalization was documented within 1 week in one patient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189604 TI - Interaction of endothelin and Ca++ entry blockers on renal circulation in anesthetized rabbits. AB - We examined an interaction of endothelium-derived vasoconstrictor endothelin and Ca++ entry blockers on renal blood flow in anesthetized rabbits. A bolus intrarenal arterial injection of endothelin at doses of 10, 25 and 50 ng produced a decrease in renal blood flow with a dose-dependent fashion, while there was no change in systemic arterial pressure. A similar extent of the decrease in renal blood flow was produced at doses of endothelin 50 ng(2.0 x 10(-11)M), angiotensin II 10 ng (9.7 x 10(-12)M) and norepinephrine 250 ng (1.5 x 10(-9)M), although the decrease in renal blood flow by endothelin was sustained in contrast to angiotensin II or norepinephrine. Pretreatment with Ca++ entry blocker nifedipine (1.0 microgram/kg/min) or diltiazem (20 micrograms/kg/min) attenuated the decrease in renal blood flow and reduced the duration time. These results suggest that exogenous endothelin produces a renal vasoconstriction in vivo. However, it seems that endothelin is less potent than angiotensin II in renal circulation in anesthetized rabbits. It is also indicated that the decrease in renal blood flow by endothelin could be mediated through a common Ca++ channel pathway in renal vasculatures. PMID- 2189605 TI - An immunofluorescence study of primary anetoderma. AB - Primary anetoderma (PA) has occasionally been described in association with lupus erythematosus (LE). The present study was performed to elucidate a possible causal link between PA and LE by the use of direct and indirect immunofluorescence (IF) methods. Two patients with PA were studied. Biopsy specimens were obtained from early inflammatory and atrophic anetoderma lesions and from the exposed and unexposed uninvolved skin of each patient. The pattern of immune deposits observed in one patient was indistinguishable from that which is often seen in systemic LE, and in the other patient from that which may be observed in chronic cutaneous LE. The direct IF study also showed fibrillar immune deposits in the dermis that resembled elastic fibres morphologically. The indirect IF study, however, failed to demonstrate anti-elastic fibre antibodies in the patients' sera. The results of this study and a review of the literature suggest that some cases of PA have direct IF findings similar to those of either chronic cutaneous or systemic LE. However, these findings, along with the serological findings, are insufficient to establish a diagnosis of LE in most of these PA cases. PMID- 2189606 TI - Pemphigoid gestationis and neonatal alloimmune thrombocytopenia. AB - A patient whose second, third and fourth pregnancies were complicated by alloimmune thrombocytopenia, developed pemphigoid gestationis after the fourth pregnancy. The infant was delivered by Caesarean section at 34 weeks gestation. The pemphigoid gestationis resolved promptly after a short course of systemic corticosteroids. A possible association between these two uncommon conditions is discussed. PMID- 2189607 TI - Speckled compound naevus. AB - We report a case of a localized speckled compound naevus arising within normally pigmented skin. Speckled melanocytic naevi are reviewed and the distinctive features of the case enumerated. PMID- 2189608 TI - Mechanisms involved in the stimulation of aldosterone production by angiotensin II, vasopressin and endothelin. AB - 1. Endothelin (ET), vasopressin (VP) and angiotensin II (AII) all stimulate aldosterone production in adrenal glomerulosa cells but the response to AII is greater than that to either ET or VP. 2. Total inositol phosphate responses to AII and ET were similar but the response to VP was lower. 3. Cytosolic free Ca2+ responses to AII were higher than to either of the other peptides. 4. Metabolism of 145IP3 was different under stimulation by the three different peptides. 5. Adrenal glomerulosa cells can distinguish between three different agonists which stimulate phosphatidylinositol turnover and produce a selective response to each peptide. PMID- 2189609 TI - Mechanisms of the effects of endothelin on responses to noradrenaline and sympathetic nerve stimulation. AB - 1. The effects of endothelin (0.1-1 nmol/L) and the phorbol ester, phorbol 12 myristate 13-acetate (PMA, 0.1-100 nmol/L) have been studied on vasoconstrictor responses to sympathetic nerve stimulation and noradrenaline in the rabbit isolated ear artery. 2. Endothelin (0.1 nmol/L) significantly enhanced the biphasic response of the arteries to a prolonged period of sympathetic nerve stimulation (2 Hz for 60 s). Both the component of the response attributable to mobilization of intracellular calcium (phasic response) and the component due to the influx of extracellular calcium (tonic response) were enhanced. 3. PMA (0.1 and 0.3 nmol/L), which activates protein kinase C, enhanced vasoconstrictor responses to noradrenaline but a higher concentration of PMA (100 nmol/L) inhibited responses to noradrenaline. 4. It is concluded that the enhancement of responses to sympathetic nerve stimulation and noradrenaline produced by endothelin may be due to facilitation of the influx of extracellular calcium and to the activation of protein kinase C. PMID- 2189610 TI - Endothelin stimulates inositol phosphate accumulation in rat right and left atria: a comparison with noradrenaline. AB - 1. The effect of endothelin on phosphatidylinositol turnover in rat atria was investigated by measuring the generation of inositol phosphates following [3H] inositol labelling. 2. In the presence of 10 mmol/L LiCl, endothelin caused dose dependent increases in the accumulation of inositol mono, bis and trisphosphates which were maximal at 10(-6) mol/L endothelin. The dose-response relationship was similar in right and left atria, but right atria showed a higher maximal inositol phosphate response. 3. Endothelin produced a rapid and transient stimulation of inositol trisphosphate accumulation, which peaked at 15 s followed by a slower increase which continued linearly past 20 min. 4. The time course of inositol trisphosphate release under noradrenaline stimulation showed a similar profile but the maximum stimulation was smaller than endothelin. 5. As with endothelin, responses to noradrenaline also were higher in right atria compared with left atria. 6. These data demonstrate that endothelin receptors in rat atria are coupled to the stimulation of the phosphatidylinositol turnover pathway in an essentially similar manner to alpha 1-adrenoceptors. The phosphatidylinositol pathway may be important in mediating the reported cardiac actions of endothelin. PMID- 2189611 TI - Right ventricular infarction. AB - Right ventricular infarction commonly occurs in association with acute inferior left ventricular infarction, but is uncommon when infarction involves other areas of the left ventricle. Evidence of right ventricular infarction often can be detected by physical examination, electrocardiography, echocardiography, or radionuclide ventriculography. However, hemodynamically significant infarction (i.e., hypotension or shock) is much less frequent, occurring in approximately 10% of patients with other evidence of right ventricular infarction. Right ventricular infarction increases ventricular stiffness, thereby impeding diastolic filling. This results in hemodynamic changes similar to those found in constrictive pericarditis: elevated systemic venous pressure, a Y descent greater than the X descent, and an inspiratory increase in venous pressure. The increase in venous pressure generally equals or even exceeds left atrial pressure. When hypotension or shock occurs, expansion of vascular volume is generally employed as initial therapy. In nonresponders, dobutamine or similar inotropic agents may be helpful. The prognosis during the acute phases is guarded, but, in survivors, prognosis is favorable and generally related to the extent of left ventricular involvement. PMID- 2189612 TI - Aortic and large artery stiffness: current methodology and clinical correlations. AB - Current methodology for the in vitro determination of aortic and large artery stiffness is reviewed and involves three approaches: (1) the estimation of distensibility by pulse wave velocity measurement; (2) the estimation of distensibility from the fractional diameter change of a given arterial segment by imaging techniques (e.g., angiography, Doppler ultrasound) against pressure change; (3) the estimation of compliance by determining volume change against pressure change in the arterial system during diastolic runoff from the Windkessel model of the circulation. Clinical correlations may be summarized as follows: (1) age: a progressive stiffening on aging due to structural changes up to the seventh decade; (2) sex: a lower degree of stiffness in women until menopause, after which they show an accelerated stiffening, catching up with men by the seventh decade; (3) atherosclerosis: a dissociation between degree of stiffness and extent of atherosclerosis, with a suggestion that in advanced atherosclerosis the extensive calcification may lead to increased stiffness; (4) coronary disease: an inconsistent correlation by pulse wave velocity studies, but a strongly positive correlation by angiographic study of the aortic root; (5) diabetes mellitus: a significant correlation by pulse wave velocity study, particularly in the presence of advanced peripheral vascular disease; (6) hypertension (both essential and elderly patients with systolic): positive correlation but only referable to the stiffening effect of a higher mean arterial pressure (i.e., unrelated to structural changes), although an experimental study did show a loss of compliance unrelated to the mean arterial pressure level in baboons with chronic renovascular hypertension. PMID- 2189613 TI - Captopril improves hemodynamic response to static exercise in patients with congestive heart failure: a double-blind, placebo-controlled, randomized trial. AB - Systemic and peripheral hemodynamic response to isometric exercise by handgrip test at 30% maximal voluntary contraction (MVC) for 3 minutes was assessed in 16 patients with congestive heart failure (CHF) after short-term treatment with either captopril or placebo given according to a double-blind, randomized, cross over sequence. During placebo, isometric exercise increased blood pressure (BP) and total peripheral vascular resistance (TPVR) and decreased cardiac index (CI). Captopril reduced the pressor response to exercise (mean +/- SD) (% systolic: from 14.7 +/- 6 to 11.7 +/- 3; p less than .05/% diastolic: from 12.4 +/- 4 to 8 +/- 3; p less than .005) and increased CI (from 2.3 +/- .6 to 2.6 +/- .9 liters/min/m2; p less than .01) whereas TPVR remained virtually unchanged (from 1479 +/- 597 to 1594 +/- 692 U; NS). The changes in mean BP after exercise were inversely related to the early increase in forearm blood flow (FBF) in exercising forearm during both placebo (r = .67) and captopril (r = .71). The extent of reduction in mean BP response after captopril was inversely related to the extra increase in exercising FBF determined by the drug when compared to placebo (r = .73). We conclude that captopril is able to improve the hemodynamic response to static exercise in patients with CHF, probably by increasing the blood supply to exercising muscles during contraction, thus blunting the extent of reflex pressor response. PMID- 2189614 TI - Mexiletine: pharmacology and therapeutic use. AB - Mexiletine is a Class IB antiarrhythmic which has basic and clinical electrophysiologic properties similar to lidocaine. Like other Class I antiarrhythmic agents, mexiletine blocks the rapid inward sodium current responsible for phase 0 of the action potential. It has been noted in the clinical electrophysiology laboratory to have minimal effect on sinus node function and AV nodal and His-Purkinje system conduction. Pharmacokinetic studies have shown that oral absorption is rapid with bioavailability of 80-90%. Mexiletine is predominantly metabolized by the liver with elimination half-life of 9 to 12 hours. The antiarrhythmic effects of the primary drug's metabolites remain to be defined. Hemodynamic studies have shown mexiletine to have a lesser negative inotropic effect than procainamide or disopyramide. Although mexiletine as a single agent successfully suppresses 60 to 80% of spontaneous ventricular arrhythmias, it has lower efficacy in suppression of induced ventricular arrhythmias. Multiple studies have shown that as monotherapy mexiletine is effective in preventing the induction of ventricular tachycardia in approximately 20% of patients. When used in combination with a Class IA antiarrhythmic drug for suppression of induced ventricular arrhythmias, multiple investigators have reported greater efficacy. Neurological side effects (tremor, dizziness, memory loss) occur in approximately 10% of patients while gastrointestinal side effects (nausea, anorexia, gastric irritation) occur in up to 40% of patients. Proarrhythmia or other serious toxicity from the drug is uncommon. PMID- 2189615 TI - T. Duckett Jones and his association with Paul Dudley White. PMID- 2189616 TI - Overview of the clinical development of quinapril. AB - Quinapril hydrochloride is the newest member of a family of angiotensin converting enzyme (ACE) inhibitors. On completion of laboratory and animal studies, a clinical program was initiated to evaluate the antihypertensive and other properties of the drug in human subjects. The initial phase of clinical development was concerned with the pharmacokinetics and pharmacology of quinapril. The latter studies established a dose range for the drug and explored its effect on human hemodynamics and blood pressure. Safety and interactions with other drugs were also examined. Subsequent studies explored the safety and efficacy of quinapril in patients with mild to moderate hypertension and, later, in patients with more severe hypertension. Results of these studies supported the recommendation of a once daily dosage of quinapril, 10-40 mg, as first-line therapy in the management of hypertension, with diuretics as concomitant therapy as required in patients with severe hypertension. Quinapril has also been found to be the most potent of all available ACE inhibitors in binding to tissue ACE, which may contribute to its potent and sustained duration of action. Clinical evaluation of quinapril has also been undertaken in patients with congestive heart failure. Initial findings indicate that doses of 10-20 mg/day, given twice daily, are therapeutic when administered with diuretic or digitalis. Safety of the drug has been established in 2700 patients. PMID- 2189617 TI - The safety and efficacy of quinapril in the treatment of mild to moderate essential hypertension. AB - Major clinical trials are reviewed comparing the efficacy and safety of quinapril hydrochloride, a new nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor, with that of placebo, captopril, and enalapril in the treatment of mild to moderate essential hypertension. A randomized, double-blind 12-week study of 270 patients compared the efficacy of placebo with once or twice daily doses of quinapril (20, 40, 80 mg/day, with forced titration). Quinapril effectively lowered both diastolic blood pressure (DBP) and systolic blood pressure. Mean reductions in DBP of up to 13 mmHg from baseline were obtained. At full dosage, more than 65% of patients achieved a clinically significant reduction in DBP. Quinapril was similarly effective whether the total daily dose was given once or twice daily. In a multicenter, double-blind study involving more than 400 patients, the efficacy of quinapril (10-40 mg/day, given once or twice daily) was found to be similar to captopril (25 mg bid to 50 mg tid). Hydrochlorothiazide (HCTZ) safely provided additive effects when given to nonresponders in both treatment groups. In a 28-week double-blind study of 258 patients comparing the efficacy of quinapril or enalapril at doses of 10, 20, and 40 mg/day (with optional titration), quinapril was found to be of similar efficacy as enalapril. The large majority of patients on either regimen were controlled with monotherapy. HCTZ again safely provided additive effects. Quinapril was well tolerated in all trials, with the incidence of adverse events and withdrawals tending to be lower with quinapril than with enalapril or captopril. PMID- 2189618 TI - The efficacy and safety of quinapril in the treatment of moderate to severe and severe hypertension: comparison to captopril. AB - Major studies comparing the efficacy and safety of quinapril and captopril in the treatment of moderate to severe or severe hypertension are reviewed. Given concurrently with hydrochlorothiazide 25 mg/day to patients with moderate to severe hypertension, quinapril 20-80 mg/day twice daily was found to be more effective than captopril 50-200 mg/day twice daily, and quinapril 10-40 mg/day once daily was found to be as effective as captopril 25-100 mg/day twice daily. Given as initial monotherapy to patients with severe hypertension, quinapril 10 40 mg/day twice daily was found to be as effective as captopril 50-200 mg/day twice daily. Quinapril was found to be well tolerated, both when administered against a diuretic background and when diuretic was added to a quinapril regimen. PMID- 2189619 TI - ACE inhibitors in the treatment of heart failure. AB - The renin-angiotensin-aldosterone system (RAAS) has been implicated in the pathogenesis of congestive heart failure (CHF). Abnormal activation of the RAAS adversely affects cardiac performance and impairs functional status, increasing both afterload and preload through direct and indirect mechanisms. Conventional first-line therapy for CHF consists of diuretics and/or digitalis. Diuretics offer rapid relief of symptoms, effective volume control, and ease of administration, but are associated with a number of disadvantages, including further activation of neurohormonal systems resulting in augmented vasoconstriction. Angiotensin-converting enzyme (ACE) inhibitors, which block the RAAS by inhibiting production of angiotensin II from angiotensin I, are emerging as the vasodilators of choice in combination with diuretics with or without concomitant digitalis. Direct comparative studies have shown that ACE inhibitors provide acute and long-term symptomatic, hemodynamic, and exercise-related benefits as well as improved functional class and, possibly, slowed progression of disease with enhanced survival in specific subgroups. Captopril was the first orally effective ACE inhibitor associated with improved exercise tolerance and functional class in large multicenter trials of patients with severe heart failure and mild to moderate heart failure. Enalapril reduced the probability of death in patients with severe heart failure in the CONSENSUS trial. The new ACE inhibitor quinapril has been shown to improve hemodynamic status both acutely and chronically and to produce dose-related improvements in exercise tolerance. ACE inhibitors have a favorable safety profile, although hypotension can occur with initial doses, particularly in volume-depleted patients or at times when excessive initial doses are administered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189620 TI - The safety profile of quinapril: is there a difference among ACE inhibitors? AB - The safety of quinapril hydrochloride, a new nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor with an intermediate duration of action, has been evaluated in 3,031 patients with hypertension and congestive heart failure (CHF) and has been compared with other ACE inhibitors. A comparison of double-blind studies showed quinapril to have a lower incidence of adverse effects and withdrawals than reported for captopril or enalapril. Analysis of onset of adverse events or withdrawals did not show either a time-dependent or dose dependent relationship with quinapril. The proportion of patients who experienced orthostatic hypotension was less than that of patients on captopril or enalapril. Double-blind, long-term, and open-label studies with quinapril showed no increase in the incidence of events reported in patients with CHF compared with hypertensive patients. Quinapril produced minimal adverse effects on renal function in both patients with normal renal function and in those with pre existing renal impairment. Age analysis of data from all studies showed no increase in total reporting of adverse events in older patients who did not take concomitant diuretics. PMID- 2189621 TI - The effects of ACE inhibitors and other antihypertensive drugs on cardiovascular risk factors and atherogenesis. AB - The effects of antihypertensive therapy on the atherosclerotic process and differences among various treatment approaches have been studied in several animal models. Studies in cholesterol-fed rabbits have indicated that beta blockers and calcium antagonists can inhibit the development of aortic atherosclerosis induced by marked hypercholesterolemia. However, no such antiatherosclerotic action has been apparent with these agents in the Watanabe heritable hyperlipidemic (WHHL) rabbit. A study was conducted to determine the effects of the angiotensin-converting enzyme (ACE) inhibitor captopril administered orally for 9 months on the development of atherosclerosis in normotensive WHHL. Compared with controls, the treated animals had a significant reduction in atherosclerosis of the descending thoracic aorta. These effects were associated with significantly lower blood pressure, though within the normal range, in captopril-treated versus control animals. In the captopril group, the atherosclerotic plaques were thinner and less cellular than plaques of similar gross severity in control WHHL. The findings indicate that the ACE inhibitor captopril can inhibit atherogenesis in the WHHL, which has been resistant to such therapy with other antihypertensive drugs. PMID- 2189622 TI - The role of ACE inhibitors in the treatment of arrhythmias. AB - Several experimental models have been studied to determine the role of angiotensin-converting enzyme (ACE) inhibitors in reducing ischemic and reperfusion arrhythmias. Studies of left main coronary artery occlusion in isolated perfused rat hearts have shown that the ACE inhibitor captopril reduced reperfusion ventricular fibrillation from 100% to 0% and was associated with a reduction in purine overflow and in norepinephrine release. These effects were abolished in the presence of indomethacin. In an anesthetized rat model of acute myocardial infarction (MI), ACE inhibition reduced mean duration of ventricular fibrillation from 1,133 to 135. ACE inhibition at programmed electrical stimulation of the heart in a closed-chest pig model of acute MI reduced the inducibility of sustained, reproducible ventricular tachycardia from a mean of 42 to 8%. In this model, ventricular tachycardia could not be provoked in animals treated with captopril from the time of acute ischemia. Studies on the rate of ventricular ectopy in patients with poor left ventricular function have demonstrated a significant reduction with ACE inhibition. However, while a protective effect has been shown, the mechanism of action is still speculative. PMID- 2189623 TI - Quinapril: overview of preclinical data. AB - Quinapril hydrochloride, a new, orally active, nonpeptide, nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor, has been studied extensively in a variety of in vitro and in vivo animal models. Quinapril inhibits the contractile and pressor effects of angiotensin I in rabbit aorta and in rats, respectively, and lowers blood pressure in both high- and normal-renin rodent and diuretic treated dog models of hypertension. No tolerance to the antihypertensive effects of quinapril was noted in spontaneously hypertensive rats treated with quinapril for up to 14 consecutive days. As with other ACE inhibitors, quinapril had virtually no effect on the development of hypertension in the renin-independent one-kidney deoxycorticosterone (DOCA)-salt hypertensive rat. Antihypertensive activity best correlates with the inhibition of tissue (vascular) ACE, and thus the reduction in peripheral vascular resistance associated with plasma and tissue ACE most likely accounts for the therapeutic benefit of quinapril. Preliminary data from a trial of quinapril in cardiomyopathic hamsters show that the drug prevents the anticipated decline in left ventricular contractile function and retards the temporal progression of left ventricular failure. ACE inhibitors have been found to have a lipid-neutral profile, unlike some other classes of antihypertensives. Quinapril is rapidly absorbed and extensively distributed to all tissues except brain. It is rapidly hydrolyzed to quinaprilat, its pharmacologically active diacid form. Metabolism to other compounds is not extensive. Quinapril's preclinical toxicologic profile is similar to that of other ACE inhibitors. Long-term toxicology studies show that quinapril is not teratogenic, carcinogenic, or mutagenic. PMID- 2189624 TI - Topical alpha interferon in the treatment of oral ulcers in Behcet's syndrome: a preliminary report. AB - The effect of topical recombinant interferon alfa 2c hydrogel (IFN alpha 2C) in the aphthous lesions of the mouth in Behcet's syndrome was assessed in twenty patients in a twelve-week open trial. IFN alpha 2C applied to the mouth for four weeks significantly reduced the number of aphthae in the post-treatment phase compared to the pretreatment and treatment phases. No side effects were recorded. Topical IFN alpha 2C seems to be effective in the treatment of the aphthae in Behcet's syndrome. PMID- 2189625 TI - Serological and immunohistochemical determination of von Willebrand factor antigen in serum and biopsy specimens from patients with arteritis temporalis and polymyalgia rheumatica. AB - Von Willebrand factor antigen (vWF-Ag) levels in serum from patients with untreated polymyalgia rheumatica (PMR) and arteritis temporalis (AT) were measured using an ELISA technique. The level in patients with AT was significantly higher (median 229%, range 182-358%) than in patients with PMR (median 190%, range 131-390%) and in controls (median 179%, range 65-296%). Using an immunoperoxidase technique and biopsy specimens from 21 temporal arteries (7 patients with AT, 7 with PMR and 7 with other diseases), vWF-Ag was localized in the luminal endothelium in all cases. VWF-Ag was also present in many new vessels along the lamina elastica of the artery wall in all patients with AT, but not in patients with PMR. We relate the higher vWF-Ag level in these patients to an increased vWF-Ag production by endothelian cells in new, proliferating vessels in the artery wall. PMID- 2189626 TI - A short review of the relationship between intestinal permeability and inflammatory joint disease. AB - The potential aetiological relationship between increased intestinal permeability and inflammatory joint disease is reviewed. The known physiology of intestinal permeability is outlined and the alterations which occur in different disease states are described. A rationale is given for the hypothesis that the gut is the likely source of the antigens causing inflammatory arthritis, and the studies of this hypothesis to date are reviewed. PMID- 2189627 TI - Total arthroplasty in Paget's disease of the hip. A clinical review and review of the literature. AB - The results in 30 Paget's disease patients with 37 affected hips treated with total hip arthroplasty (THA) for symptomatic coxarthrosis were compared with the results of previously reported series. Metabolic activity of the disease subsequent to surgery seemed to have no effect on the clinical outcome during 7.8 years of follow-up study; location of the disease (acetabulum only, femur only, or both) or the presence of protrusio alone also had no effect. For the femur, failure rates were similar for prostheses implanted in Pagetic or non-Pagetic bone. Good results can be anticipated for patients with Paget's disease treated with cemented THA. PMID- 2189628 TI - Femoral vein occlusion during hip arthroplasty. AB - The mechanism of femoral vein occlusion when the hip joint is dislocated and manipulated during arthroplasty has been studied in fresh anatomic specimens. Flow studies show that moderate degrees of flexion and adduction in association with dislocation obstruct venous flow just distal to the femoral sheath at normal pressures and flow rates. Internal femoral rotation during a posterior approach to the hip causes "scissoring" of the femoral vein between femur and pubic bone. External femoral rotation during an anterior approach does not occlude flow. Injection of Batson's acrylic and neoprene latex showed that obstruction is also due to about 4 cm of shortening caused by proximal migration of the femur after dislocation in association with adduction and flexion. The femoral vein in the unsupported segment distal to the femoral sheath subsequently buckles and kinks. During operative manipulation, intermittent obstruction at this level is therefore likely to cause intermittent venous distension distally. This mechanism depletes the femoral vein of fibrinolytic activity distal to the occlusion and may explain the incidence of deep femoral thrombosis peculiar to this procedure. PMID- 2189629 TI - Late-onset tibia vara (Blount's disease). Current concepts. AB - Idiopathic tibia vara or Blount's disease can be classified into three age-onset groups: (1) infantile, less than three years; (2) juvenile, four to ten years; and (3) adolescent, 11 years or older. The latter two groups comprise late-onset tibia vara, which is much less common than the infantile-onset form. In a comparison of eight juvenile-onset patients (13 knees) and seven adolescent-onset patients (nine knees), there were essentially no significant clinical, roentgenographic, or physeal-histopathologic differences. Both groups had severe obesity, mild to moderate varus deformities, and less-pronounced roentgenographic characteristics. Histopathologic analyses of the entire physis from the proximal tibia in five cases (seven knees) were essentially identical in patients with the infantile form as well as in those with slipped-capital femoral epiphyses, suggesting a common etiology. Recurrence of deformity after surgical correction occurred frequently in the juvenile onset males but not in juvenile onset females or the adolescent onset group. Incomplete correction of the varus deformity occurred more frequently in the latter group. The etiology for tibia vara appears to involve varus stress growth suppression, and disruption of endochondral ossification. The major differences between the three groups is due to the age at clinical onset, the amount of remaining growth, and the magnitude of the medial compression forces across the medial aspect of the knee. PMID- 2189630 TI - Collagens synthesized by healing fractures. AB - Several extracellular matrices are formed by healing fractures, and the collagens within these matrices have been identified in rabbit and rat fracture models. Type III collagen is the major collagen of the fibrous matrix that forms along the periosteal surface. Type I collagen is secreted in large amounts as trabeculae of bone develop within the fibrous tissue. Type V collagen is found in both the fibrous tissue and bone; it is particularly associated with blood vessels. Type II collagen is the last of the major collagens to be synthesized; its synthesis is dependent on the mechanical conditions under which the fractures are healing. A large area of cartilage, and hence of Type II collagen, is formed only if the fracture is mechanically unstable. Of the minor collagens, only Types IX and X have been identified to date. Type IX collagen is present throughout the large areas of cartilage, and Type X is present only in calcified regions. The matrices are compared with those produced during embryonic limb development. Although cartilage in the embryo provides a rapidly growing model of the future bone, in healing fractures cartilage is produced only where the cellular environment precludes the differentiation of osteoblasts. The effects of mechanical stability on the matrices support and illustrate this conclusion. PMID- 2189631 TI - Osteochondritis dissecans in children. 1952. PMID- 2189632 TI - Calcium and bone metabolic homeostasis in active and denning black bears (Ursus americanus). AB - Decreased mechanical use of the skeleton results in osteoporosis in all species that have been studied, including humans. The unique metabolic adaptations of denning bears, however, suggest that these animals have evolved osteoregulatory mechanisms to protect against osteoporosis. The authors studied calcium and bone metabolism in black bears during three seasons: summer, winter, and spring. The serum calcium concentration did not change despite the fact that the bears remained metabolically active, recumbent, and anuric for four months. Furthermore, after four months of skeletal inactivity, bone mass and other parameters of osseous metabolism, including bone formation and mineral apposition rates were unchanged over summer values. A hypermetabolic state was observed after spring arousal in response to resumed skeletal loading. These findings suggest that bears may produce an osteoregulatory mechanism that prevents bone loss during prolonged periods of skeletal inactivity. Such a substance could have potential therapeutic applications for human beings. PMID- 2189633 TI - Patellofemoral pain in children. AB - The primary inadequacy in the treatment of patellofemoral pain in children has been the inability to translate distinct problems recognized during physical examination into a specific clinical classification. Using a classification system based on etiology rather than symptoms allows the clinician to proceed with treatment based on a specific diagnosis. The majority of patellofemoral pain in children is caused by trauma and malalignment syndromes (or a combination of both) and can usually be managed successfully with nonoperative methods. Success in a rehabilitation program depends on a precise understanding of the original or underlying cause of the child's patellofemoral pain. PMID- 2189634 TI - Ligamentous injuries of the knee in children. AB - Ligamentous injuries, although uncommon in the skeletally immature patient, can be found in isolation or associated with physeal injury or long-bone fracture. Four new cases of ligamentous injury in the child show that recognition and management of these injuries are important to achieve good recovery. In addition to history and physical examination, standard and stress roentgenographs, examination under anesthesia, and arthroscopy are important for early diagnosis. PMID- 2189635 TI - Tumors about the knee in children. AB - Tumors are rare causes of knee symptoms in children but must be considered in the differential diagnosis of pediatric knee pain in order to avoid errors in treatment that could result in loss of limb or even life. Experience with 199 bone and soft-tissue tumors about the knee in children are reviewed. The majority of lesions were benign bone tumors (n = 101), with osteocartilaginous exostoses, nonossifying fibromas, and chondroblastomas predominating. Malignant bone tumors (n = 59) were less frequent, and osteosarcoma (n = 48) was by far the most common sarcoma. Soft-tissue lesions (n = 31) were much less frequent and included rhabdomyosarcoma, synovial sarcoma, fibrosarcoma, and desmoid tumors. A careful history, physical examination, and review of roentgenograms are essential to avoid errors in diagnosis. Malignant tumors require roentgenograms and laboratory studies in sequence to stage the patient. A properly performed biopsy established the diagnosis in most instances. Popliteal cysts, stress fractures, infection, myositis ossificans, histiocytosis, and other lesions can mimic tumors and delay correct diagnosis. PMID- 2189636 TI - A hierarchy of values in the design and construction of the ear. AB - A brief outline of the structure of the ear is presented, indicating that there is a hierarchy of importance to the various components of the ear in reconstruction. Consideration of fundamental shape, size, and position of the ear and its parts would be of use in various surgical procedures. PMID- 2189637 TI - Anatomy of the auricle. AB - A fundamental knowledge of anatomy of the ear aids in the performance of periauricular surgery. Details of vascular anatomy may help in replantation and reconstruction of the auricle, and in the use of the retroauricular free flap. PMID- 2189638 TI - Anthropometry of the normal and defective ear. AB - Surface measurements of the ear are needed to assess damage in patients with disfigurement or defects of the ears and face. Population norms are useful in calculating the amount of tissue needed to rebuild the ear to adequate size and natural position. Anthropometry proved useful in defining grades of severe, moderate, and mild microtia in 73 patients with various facial syndromes. The division into grades was based on the amount of tissue lost and the degree of asymmetry in the position of the ears. Within each grade the size and position of the ears varied greatly. In almost one-third, the nonoperated microtic ears were symmetrically located, promising the best aesthetic results with the least demanding surgical procedures. In slightly over one-third, the microtic ears were associated with marked horizontal and vertical asymmetries. In cases of horizontal and vertical dislocation exceeding 20 mm, surgical correction of the defective facial framework should precede the building up of a new ear. Data on growth and age of maturation of the ears in the normal population can be useful in choosing the optimal time for ear reconstruction. PMID- 2189639 TI - Overview of experience of Tanzer's group with microtia. AB - A review of our patients since Dr. Tanzer's retirement in 1970 shows good and lasting results after reconstruction of microtia using autogenous cartilage frameworks and staged procedures. There has been no evidence of shrinkage or distortion of the cartilage in any of our own patients, and the majority of them are pleased with their ears. With a cooperative and well-motivated patient and surgeons who are skilled and experienced in the procedure, ears can be made with a relatively normal size, shape, and position to match closely the other side. We continue to feel strongly that autogenous cartilage is the safest and best material to use for the ear framework. At some time in the future the body may be taught to accept homografts as if they were its own tissue, and allografts may be available that are tolerated as well as living tissue. Until then we will rely on autogenous tissue and our present techniques, which have produced long-lasting good results. Altogether the combined experience with ear reconstruction of Tanzer's group at the Dartmouth-Hitchcock Medical Center spans more than 30 years. PMID- 2189640 TI - Long-term evaluation of modified Tanzer ear reconstruction. AB - This article presents the author's experience using the Tanzer technique with modifications. Included also are changes in technique based on results from long term follow-up studies. PMID- 2189641 TI - One-stage total reconstruction of the ear with simultaneous tympanoplasty. AB - The one-stage total ear reconstruction (auricular reconstruction and tympanoplasty) has a number of merits. 1. Satisfactory esthetic results obtained in one operation. 2. The "super thin" skin flap is elevated on a plane that excludes hair follicles from the flap, so the hair-bearing areas of the scalp can be readily incorporated as part of the ear reconstruction. 3. The reconstructed ear has adequate blood supply and protective sensation. 4. The surgeon may choose to carry out a tympanoplasty and obtain restoration of auditory function or may choose to carry out a pseudomeatus procedure and reduce the operating time. We feel that the "super thin" skin flap and the simultaneous tympanoplasty are valuable supplements to ear reconstruction. The functional results of the tympanoplasty must be considered only a partial success at this time; long-term evaluation as well as technologic improvements are needed. PMID- 2189642 TI - Technique of total ear reconstruction with open framework, composite pseudomeatus graft, and postauricular transposition flap. AB - Modifications of Tanzer's technique of total reconstruction of the auricle are described, emphasizing the construction of a deep conchal cavity and pseudomeatus, with ample projection of the auricle. To obtain a more prominent projection of the auricle, a transposition flap from retroinfra-auricular skin is used, with placement of small cartilage props beneath the framework. The depth of the conchal cavity is enhanced by excavation of soft tissues and placement of an additional cartilage graft at the posterior wall of the choncha. The external meatus is imitated by a cone-shaped composite graft taken from the cymba of the opposite ear. PMID- 2189643 TI - Staged, laminated, costal cartilage framework for ear reconstruction. AB - Two features of greatest importance in achieving a normal appearance in the reconstruction of an ear with microtia are that a conchal component with sufficient size, shape, and depth is present; and that auricular projection, sufficient in degree to show contours that appear normal from a posterior view, is present. The authors describe the construction of a staged, laminated framework that helps achieve these goals. PMID- 2189644 TI - Reconstruction of microtia. Pursuing a natural appearance. AB - We have designed a "contour-accentuated" auricular framework in which the depth and height of the relief of the contours have been exaggerated to improve the illusion of three-dimensional topography. In one technique, the "full framework," a large amount of supplemental skin coverage is needed, and this is provided by a superficial temporal artery flap surfaced with postauricular skin and groin skin. In the second type, the "low-profile framework," the supplemental skin graft requirement is less and is provided by local subcutaneous tissue flaps in the conchal-tragal area. These are surfaced with postauricular skin. These steps have improved our ability to provide a three-dimensional quality to ear reconstruction in microtia. PMID- 2189645 TI - Complications of surgery of the external ear. AB - The external ear has intrinsic anatomical vulnerabilities that invite surgical complications. Among these are the exposed position of the auricle, the thinness of the skin, and subcutaneous cover; the delicate convoluted shape; and the avascularity of the underlying auricular cartilage. Certain complications of surgery such as infection, bleeding, and hypertrophic scars are shared in common with operative procedures elsewhere on the body. Other complications are specific to otoplasty, to ear reconstruction, and to other individual ear procedures. This article outlines the means of recognition, treatment, and prevention of complications in surgery of the external ear. PMID- 2189646 TI - The role of tissue expansion in reconstruction of the ear. AB - The following guidelines are suggested for the use of tissue expansion in ear reconstruction based on both personal experience and my evaluation of the reported results of expansion in the hands of other surgeons experienced in ear reconstruction: 1) Cases should be carefully selected to avoid those with excess scarring from previous surgery or trauma as well as avoid the other common contraindications to the use of tissue expansion. 2) In most congenital cases the expander should be placed through a remote incision within the postauricular hairline, and excision of the cartilage vestige delayed until expansion is completed and the framework is ready for placement. 3) A remote valve expander of a crescent shape with a volume of 60-100cc is ideal; low profile expanders may even be safer. 4) The pocket for the expander should be dissected immediately above the fascia and against the cartilage remnant. 5) Rapid expansion should be avoided; ideally injections should be carried out one time each week and with relatively small quantities (5-10cc per injection). 6) At the time of expander removal and placement of the cartilage framework the capsule should be meticulously excised to allow tight skin-cartilage coaptation. This is further enhanced by effective suction drainage following wound closure. PMID- 2189647 TI - Tissue expansion in reconstruction of acquired auricular defects. AB - Over the past 10 years, tissue expansion has gradually become accepted as a useful adjunct to ear reconstruction with an autologous framework. The advantage of expanded tissue in these cases has been the addition of more tissue with similar color, texture, and sensation. In traumatic cases, the creation of well vascularized tissue allows an improved anterior draping of skin over the cartilaginous framework and production of a well-defined posterior sulcus. Encroachment of hair onto the reconstructed ear is minimized because of the extra tissue produced by expansion. Under favorable conditions, tissue expansion is an acceptable and reliable method for partial or total ear reconstruction. PMID- 2189648 TI - Reconstruction of microtia using tissue expander. AB - In this article, microtia was reconstructed by the use of a tissue expander to obtain a sufficient temporal skin flap that ensures an acceptable contour of the auricle. This article introduces the operative procedure and the authors' experience. PMID- 2189649 TI - Osseointegrated implants for replacement of absent or defective ears. AB - Tissue-integrated skin-penetrating implants placed in the mastoid process have been used in 94 patients for the retention of silicone rubber auricular prostheses. The surgery is performed in two stages with a 3- to 4-month interval between the first and second stage in order to establish osseointegration. During the first stage, implants made out of commercially pure titanium are placed in the bone. A gentle surgical technique is imperative in order not to damage the osteocytes, which might otherwise result in a fibrous encapsulation instead of a direct contact between implant and bone (osseointegration). The implants are handled with titanium-coated instruments only, and never by the gloved hand directly. Even minute sterile contaminants on the surface of the implant may jeopardize osseointegration. The skin penetration is performed during the second stage. This procedure includes a subcutaneous tissue reduction aimed at reducing mobility between the implant and the skin. To facilitate cleaning, the skin should be devoid of hair follicles. If necessary, a hairless skin graft from the upper arm is used. Three to four weeks after the second stage, the healing has normally reached the point at which the prosthesis can be made and attached to the implants. The frequency of adverse skin reactions around the penetration has been registered carefully. All in all, 2458 observations were made over a 10-year period. Only 3.5 per cent of these called for active treatment. PMID- 2189651 TI - Otoplasty: a combined approach. AB - The described procedures, alone or in combination, provide the flexibility to correct the vast majority of prominent ears. The techniques are easy to learn and very reliable. The deformed scapha, hidden helix, lobule prominence, asymmetry, and recurrent deformity should become historical. An esthetic degree of protrusion and natural appearance of the reconstructed ear can be achieved in almost every case. PMID- 2189650 TI - Congenital aural atresia. AB - Close cooperation between the plastic surgeon and the otologist, with each understanding and respecting the importance of the other's role, will provide the atresia/microtia patient with the best possible chance of a successful outcome. The purpose of the atresia repair is to improve hearing. Our goal is to attain, through surgery, hearing thresholds that will enable the patient to discard his hearing aid. PMID- 2189652 TI - Nonsurgical correction of congenital auricular deformities. AB - Congenital auricular deformities are found in 55.2 per cent of neonates at birth. When the deformities are not hypoplastic, nonsurgical correction is very easy and reliable. Lop ear and Stahl's ear respond well to the nonsurgical correction only during the neonatal period, while protruding ears and cryptotia respond until approximately 6 months of age. We noticed that there are variations in the time period for response to nonsurgical correction in the different types of auricular deformities. We have continually observed the natural changes in 1000 babies' auricular shapes from birth to 1 year of age. Lop ear and Stahl's ear were auricular deformities that appeared in 47 per cent of all newborn babies. Eighty four per cent of these deformities disappeared spontaneously during the first year of life. They were present in 7 per cent of the 1000 babies at 1 year of age. On the other hand, the percentage of protruding ears increases from 0.4 per cent at birth to 5.5 per cent at 1 year of age. Our observations show that most of the protruding ears are acquired deformities. If a baby is placed in a supine position, the weight of the baby's head will fold the ear forward when the baby turns its head to one side; this is the mechanism presented as the probable cause for the acquired protruding ear. PMID- 2189653 TI - Microsurgical replantation of the external ear. AB - Cosmetically, the optimal management of the amputated external ear is microsurgical replantation. Although technically demanding, replantation is possible by the experienced surgeon. Success frequently requires the use of vein grafts, heparinization, and the alleviation of venous congestion with medicinal leeches or frequent stab wounds. PMID- 2189654 TI - Reconstruction of the ear after tumor excision. AB - Tumors of the external ear are frequent. A variety of defects, created by surgical excision, can be repaired with basic techniques under outpatient local anesthesia. Most often, the redistribution of local and adjacent tissue allows satisfactory reconstruction. PMID- 2189655 TI - Surgical aspects of single lung transplantation. AB - Single lung transplantation is a viable therapeutic option for selected patients with end-stage lung disease. The techniques described, in conjunction with rigorous preoperative physiotherapy, diligent postoperative care, immunosuppression with early avoidance of steroids, and postoperative rehabilitation, have resulted in a gratifying rate of success. Transplantation of the lung involves not a mere technical transfer of the organ from one body to another. It is a complex logistic undertaking requiring a large team of professionals who attend to the many essential components including patient selection, preoperative rehabilitation, donor selection, postoperative care, immunosuppression, rehabilitation, and long-term follow-up. The operation itself represents an integral, but small, component. PMID- 2189656 TI - Preoperative assessment for lung transplantation. AB - Lung transplantation has evolved from an intellectual curiosity to a viable therapeutic option in a selected number of patients with end-stage lung disease. The indications for single lung, double lung, or heart-lung transplantation at major North American transplant centers are presented, the selection criteria are discussed, and the standard preoperative evaluation is outlined. Utilizing these guidelines, a 1-year actuarial survival following each of these procedures of greater than 60% can be expected. PMID- 2189657 TI - The pulmonary donor. AB - This article discusses the Pittsburgh experience with the pulmonary donor and provides guidelines for the maintenance and selection of appropriate donor lungs. Criteria for the selection of the pulmonary donor include absence of radiographic abnormality, minimal ventilation-perfusion mismatch, and an absence of identifiable infection. Because early thoracic infections result in a high mortality, donors are excluded if white cells, fungi, or bacteria are noted in samples obtained from tracheal aspirates or bronchoscopic examination. A number of techniques for the procurement of donor lungs are currently satisfactory and include core cooling with the use of cardiopulmonary bypass and different hypothermic pulmonary artery flush solutions. Other clinical preservation techniques are discussed, including autoperfusion and the use of blood-based pulmoplegia and University of Wisconsin storage solution. Because so much of the outcome following pulmonary allografting is based on the quality of the donor lungs, much of the future direction in pulmonary transplantation must be directed toward a continuing investigation of better methods for selection and maintenance of the donor and ex vivo preservation. PMID- 2189658 TI - Double lung transplantation. AB - In the past 3 years we and other centers have accumulated a small experience with double lung transplantation. We continue to believe that it offers potential benefit to patients with bilateral septic lung disease and possibly to those with obstructive lung disease as well. We have encountered significant airway complications that several other centers have avoided by improved preservation and the technical modification of bilateral bronchial anastomosis. Reliable resolution of the problem of airway viability will permit more widespread application of double lung transplantation in selected patients with end-stage pulmonary disease. PMID- 2189659 TI - Heart-lung transplantation. AB - The results of combined heart-lung transplantation have continued to improve following its reintroduction into clinical practice in 1981. En-bloc implantation has an apparent protective effect on subsequent tracheal anastomotic healing. Continuing developments in immunosuppression, rejection surveillance, and organ preservation will allow the procedure to fulfill its early promise in the management of end-stage lung and heart disease. PMID- 2189660 TI - Psychiatric, psychosocial, and rehabilitative aspects of lung transplantation. AB - The psychosocial assessment of applicants to the Toronto Lung Transplant Program provides the team with a variety of information including coping style; adjustment to illness; presence and management of psychiatric disorders; ability to adhere to medical recommendations; and available social support. This information facilitates the organization of resources to match each patient's strengths and vulnerabilities. The period of awaiting transplantation may be prolonged, and is often associated with high levels of anxiety. A support group, brief individual and family psychotherapies, and pharmacologic interventions have each been useful in ameliorating symptoms of stress during this time. A physical rehabilitation program is prescribed to most candidates and contributes to improved physical endurance as well as emotional well-being. Postoperative delirium has commonly occurred in lung transplant recipients, and appears to be associated with prolonged cardiopulmonary bypass when used, the administration of cyclosporine, and other nonspecific factors. Delirium has been managed with preoperative psychologic preparation and a routine postoperative protocol using intravenously administered haloperidol. Other immunosuppressant-associated organic mental disorders have also occurred in recipients. Postoperative recovery and rehabilitation are facilitated by both the preoperative exercise program and a postoperative exercise regimen. Recovery following transplant may require abrupt adjustment to new activity levels and reintegration into social and vocational roles. After 7 months, over 50% of surviving recipients have returned to employment and most report high satisfaction with physical and emotional well being. PMID- 2189661 TI - Early postoperative management following lung transplantation. AB - The early (first 2 weeks) postoperative care of the lung transplant patient involves the management of immediate hemodynamic instability generated in some cases by cardiopulmonary bypass and in others by increases in thoracic pressure as a result of poor graft function and pulmonary noncompliance. Subsequently, emphasis is placed on the differential diagnosis and management of hypoxemia that may appear after the third day. The latter involves an appreciation of fluid balance as it relates to renal function and the knowledge and appreciation of immunosuppression. PMID- 2189662 TI - Diagnosis and management of lung allograft rejection. AB - Improvements in our understanding of the mechanisms underlying the rejection coupled with the development of novel approaches to dealing with the rejection process have allowed successful lung and heart-lung transplantation. Nonetheless, successful lung transplantation is still limited by acute rejection. This article defines the rejection process and outlines current approaches to preventing and treating this major clinical problem. PMID- 2189663 TI - Therapeutic challenges following lung transplantation. AB - Therapeutic challenges in the management of lung transplant recipients abound. Every new (and often seemingly niggling) symptom should be carefully considered as it may be the prelude to a life-threatening infection or rejection episode; the minor, but unexplained, abnormality in a laboratory result may be the precursor to a major drug reaction. Constant vigilance is critical, but most emerging crises can be successfully addressed, and the ultimate rewards are immeasurable. PMID- 2189664 TI - Infectious complications in pulmonary allograft recipients. AB - This article has outlined the features of the major types of infections encountered in pulmonary allograft recipients. Virtually any pathogen can cause infection in these immunocompromised subjects, and there is a distinct propensity for these organisms to invade the transplanted lung. As is the case with other major organ recipients, there is a temporal sequence in the types of infection lung allograft recipients contract. Bacteria are the most frequent cause of pneumonia in the first postoperative month. After this period, infection with CMV, particularly CMV pneumonitis, becomes most common. Following the "window" for CMV infection, the risk for infestation with P. carinii becomes the primary concern. The latter two types of infection pose a double risk for the recipient: (1) morbidity and mortality from the infection itself and (2) chronic rejection following on the heels of these infections and producing morbidity and mortality on its own. Pulmonary allograft recipients are also susceptible to fungi, particularly C. albicans. Although these infections rarely produce an overwhelming pneumonia, they nonetheless carry a grave prognosis because they usually become widely disseminated. Better selection of donor lungs and prophylactic measures such as the use of broad-spectrum antibiotics and amphotericin B in the early postoperative period, the use of CMV-negative blood products in seronegative recipients, and the chronic administration of trimethoprim-sulfamethoxazole have reduced the rate of infection with bacteria, fungi, CMV (primary infections only), and P. carinii, respectively. Despite these relative successes, however, the risk for infection of the allograft remains high because the defense mechanisms in the lung allograft are breached by the effects of surgery, the "allogeneic environment" in the allograft and systemic immunosuppression, and the fact that chronic rejection causes structural changes that predispose to bacterial colonization of the airways and the need for increased levels of immunosuppression. Despite the formidable barrier that infection of the lung allograft poses, the procedure of pulmonary transplantation clearly holds sufficient promise that all efforts possible should be made to hurdle this barrier. Achieving such a goal would ensure a place for pulmonary transplantation in the armamentarium of treatment for irreversible pulmonary disease. PMID- 2189665 TI - Obliterative bronchiolitis. AB - The mass of evidence suggests that OB is a manifestation of allograft rejection in the time period later than that usually associated with acute postoperative rejection. Respiratory infection may serve to amplify (and possibly trigger) this process. A maintenance immunosuppression regimen utilizing cyclosporine A, prednisone, and azathioprine appears to be much more effective than an earlier regimen utilizing only the first two drugs. Aggressive surveillance utilizing prospective measurement of pulmonary function and arterial blood gases and a willingness to look for histologic evidence of OB with the earliest symptomatology has lowered significantly the mortality and the morbidity of this disorder at Stanford and elsewhere. We believe that the current ability to treat and even reverse this serious complication brightens the prospect of heart-lung and lung transplantation for assuming a role in the medical practice of the future. PMID- 2189666 TI - Pulmonary complications following bone marrow transplantation. AB - Pulmonary complications are a common cause of morbidity and mortality after bone marrow transplantation. Some of these complications are infectious and related to the degree of ongoing immunosuppression, and thus vary with the posttransplant marrow reconstitution and the need for continued immunomodulating drugs. Noninfectious complications are related to previous chemotherapy, the transplantation protocol and conditioning regimen, and, in allogeneic transplants, the presence of graft-versus-host disease. The various complications are classified based on their timing after the transplant procedure. A diagnostic and therapeutic approach is outlined and the prognosis is discussed. PMID- 2189667 TI - Radiologic assessment after lung transplantation. AB - Radiographic studies have a major role to play in patients undergoing lung transplantation. A review of the findings associated with the reimplantation response, acute rejection, bronchiolitis obliterans, ischemia-induced air-way complications, and cyclosporine-associated lymphoma, as well as the pulmonary and cardiac change following double lung transplantation, has been presented. It should also be kept in mind that this group of patients is also subject to all of the usual problems associated with thoracic surgery, such as infection, atelectasis, pleural effusion, and pneumothorax, conditions for which radiologic assessment is crucial. PMID- 2189668 TI - European multicenter study of TRUE Test, Panel 2. AB - Panel 2 of the standardized, ready-to-apply patch test, the TRUE Test, has been evaluated on 808 patients with suspected contact dermatitis. The patients were tested with 11 different allergens and the negative control, and compared with corresponding allergens in pet. (or aq.) in Finn Chambers fixed with Scanpor. The TRUE Test, Panel 2 and the control were applied symmetrically on the upper back. Left/right application of the respective test varied at random. Most tests were removed after 48 h and evaluated after 72 or 96 h, according to generally accepted recommendations. There were positive test reactions to all 11 allergens tested in the patient group. The concordance of positive reactions (1+, 2+, 3+) was 63% between TRUE Test, Panel 2 and the control method; 17% of positive reactions occurred only with TRUE Test, Panel 2 and 20% only with the compared method. Approximately 75% of all positive test reactions were explained by the patients' present or past history. Irritant/questionable reactions occurred in the same frequency for the 2 methods. Such reactions were recorded in less than 1% of all patches applied. No late reactions were recorded. PMID- 2189669 TI - Combined sensitization to palladium and nickel. PMID- 2189670 TI - Do retroverted uteri adversely affect insertions and performance of IUDs? AB - A large international multi-center IUD data set (N = 5520) coordinated by Family Health International was analysed to determine if the uterine position of a woman (anteverted, mid-positioned or retroverted) affects the ease of IUD insertion and if knowledge of uterine position would diminish insertion-related problems and improve IUD performance. Findings showed that insertion-related events were rare irrespective of uterine position. Women with retroverted uteri were not associated with higher termination rates for accidental pregnancy, expulsion or removal for bleeding and/or pain after 12 months of IUD use, as compared to the other two uterine position groups. All insertions in this data set were performed by experienced obstetricians/gynecologists, and our findings suggest that women with retroverted uteri should be equally good candidates for IUD contraception. PMID- 2189671 TI - How important are lens oxygen ratings? Performance predictors for the concerned practitioner. AB - Three indices of oxygen passage exert considerable influence in contact lens practice: (a) Dk/L, which indicates the oxygen transmissivity of a lens; (b) equivalent oxygen percentage (EOP), which assesses corneal oxygen demand during lens wear; and (c) pachometry, a measure of the swelling response of the cornea to lens-induced hypoxia. These indices correlate well with one another but reflect different "time-line" values, with Dk/L and EOP giving predictive information about lens-eye interactions and pachometry reflecting actual wearing responses. Lens oxygen data hold tangible benefits for manufacturers, clinicians, and patients. They guide manufacturers in choosing which new lens materials to develop, in making decisions about physiologically acceptable lens thicknesses, in affirming safety and efficacy data, in securing Food and Drug Administration (FDA) product approval, and in presenting performance information to doctors and patients. Used effectively, such guidance should lower the cost of product development. Clinicians use lens oxygen ratings to refine their prescribing practices, thereby boosting patient satisfaction and lens wear success. Besides favoring long-term ocular health, oxygen ratings may yield an economic benefit for patients, if the savings realized by manufacturers during product development are translated into lower lens prices. PMID- 2189672 TI - Are hard lenses superior to soft? The advantages of soft lenses. AB - Soft lenses now account for 85% of all lens sales in the United States and 74% of all sales worldwide. Several factors account for their popularity with patients, practitioners, and lens manufacturers. For patients, soft lenses offer easier adaptation, greater comfort, better appearance, less nighttime flare and spectacle blur, more flexibility in wearing schedule, and less chance of lens loss than polymethylmethacrylate (PMMA) or rigid gas-permeable lenses. Soft lenses also provide the options of disposability and of iris color change. Practitioners prefer soft lenses because they are less likely than hard lenses to cause epithelial staining, corneal molding, corneal edema, corneal desensitivity, or lens overwear syndrome. Furthermore, soft lenses present fewer fitting problems, satisfy therapeutic needs, are easier to stock for replacement purposes, and generally require no in-office modifications. Practitioners also welcome the benefits of disposable lenses: a simple lens care regimen, a decreased potential for deposit buildup, and adaptability to many different lifestyles. Manufacturers like the fact that hydrogels can be stock molded, and that their fitting is easier to teach. PMID- 2189673 TI - Is the quality of vision with contact lenses adequate? Not only adequate but often superior. AB - Two factors govern the quality of vision with contact lenses (CLs): the fit and movement of the lens and the adequacy of its optics. Studies have not demonstrated any inherent inadequacies in material or design parameters that might account for visual difficulties in lens wearers. To the contrary, thickness, water content, and fit can be varied within clinically acceptable ranges without compromising vision. A poorly fitted lens, however, can cause excessive corneal edema and consequent visual problems. Poor vision may also result from uncorrected refractive error, the development of an unstable optical surface, or the use of a lens material that is inherently inadequate for a given patient. Such causes of visual dysfunction can usually be avoided through better fitting, better lens care, more careful refraction, or better patient-lens matching. Specialized lens designs can sometimes be used to correct vision problems. Certain types of rigid front-surface aspheric lenses, for example, provide astigmats with even better visual correction than spherical rigid lenses or spectacles, but the improvement is small and highly patient dependent. Similarly, although soft toric lenses can provide good vision, it is often technically difficult to orient and stabilize the correcting cylinder. PMID- 2189674 TI - Is the quality of vision with contact lenses adequate? Not in all instances. AB - There are several circumstances in which contact lenses (CLs) provide vision inferior to that possible with spectacles. Over time, both soft and rigid gas permeable (RGP) lenses accumulate deposits that can cloud vision. RGP lenses are especially prone to scratching; some varieties may even become crazed, giving a spiderweb quality to vision. Certain uncommon corneal complications associated with lens wear--infection, neovascularization, ulcers, and severe epithelial edema--may also impair vision, sometimes permanently. CLs often provide less than optimal vision for patients with presbyopia or severe astigmatism. Difficulties with axis stabilization arise with both soft and rigid toric lenses, and these can take several attempts to resolve. Monovision fitting currently offers the best option for presbyopes, but it has an effect on stereopsis, compromising depth perception. Furthermore, patients often require considerable time before adapting to monovision lens use. Finally, even under normal circumstances, certain inherent features of CLs can diminish visual acuity. The water in soft lenses diffuses light; the loss of visual crispness is particularly notable with high-water-content lenses. On the other hand, the small diameter of RGP lenses often contributes to ghosting--a phenomenon in which the edge of the lenses is visible whenever the pupils are widely dilated. PMID- 2189675 TI - Is daily wear better than extended wear? Arguments in favor of daily wear. AB - The use of contact lenses for extended wear appears to be accompanied by an increase in several complications, the most serious of which is corneal infection. It has been proposed that infection is due to corneal epithelial layer microtrauma and lens care system contamination, but noncompliance, contamination of care systems, and microtrauma [especially among keratoconics and polymethylmethacrylate (PMMA) lens users, for example] are so common in daily wear that we believe they are insufficient to explain the approximately sixfold increase in the rate of corneal infection with extended wear. Perhaps the chronic hypoxic stress of extended wear use of contact lenses substantially reduces the resistance of the epithelium to either injury or microbial infection. Until evidence is provided that new contact lenses have sufficient oxygen transmissibility (Dk/L) to fully satisfy corneal oxygen needs under extended wear conditions, and the extended wear use of such lenses is thoroughly tested in a study population, we believe that the majority of contact lens patients should be maintained on daily wear schedules. PMID- 2189676 TI - Is daily wear better than extended wear? A rational approach to extended wear. AB - The physiologic and anatomic effects of contact lens (CL) wear include both short and long-term changes in the corneal epithelium stroma, and endothelium. Although these effects can arise in all lens wearers, they are of greatest concern in users of extended wear lenses, owing to their association with an increased incidence of sight-threatening complications. The complications attendant on extended wear may be patient related, lens related, or care related, but they are not inevitable. Patient-related complications can be minimized if clinicians pay close attention to patient selection, lens fitting, and follow-up. Complications related to lens wear and care can be minimized if patients (a) follow the proper lens wear regimen; (b) observe appropriate lens care routines; (c) follow the proper lens disposal regimen; (d) monitor the appearance, visual acuity, and well-being of their eyes; and (e) immediately report any irregularities or changes in ocular status to their doctor. To ensure that such rules are observed, practitioners must educate their patients as well as their staff in these matters. They must also instruct patients not to wear extended wear lenses longer than 7 days at a time and to allow for an overnight respite from lens wear after this period of use. PMID- 2189677 TI - Acanthamoeba keratitis and contact lens wear: the patient is at fault. AB - The avoidance of nonsterile solutions is important to curtailing Acanthamoeba keratitis, a serious infection that has been found to occur with all types of contact lens (CL) wear. Increased patient education, revised recommendations regarding the use of tap and distilled water, and improved disinfecting systems are vital to preventing infection. These precautions are particularly important since it appears that Acanthamoeba, unlike Pseudomonas, may not require an epithelial defect to establish corneal infection and, once in the cornea, may not respond to drug therapy or surgical extirpation. Unfortunately, many patients receive poor lens care instructions or cannot be relied on to follow appropriate routines. Finding a foolproof means of lens disinfection for them is critical. Recently, several disinfection systems were tested against Acanthamoeba castellanii and Acanthamoeba polyphaga cysts and trophozoites to see which might prove most effective. Effective systems included heat disinfection at 70 to 80 degrees C for 10 min, 3% hydrogen peroxide for 2-3 h, 0.001% thimerosal with edetate for 4 h, 0.005% benzalkonium chloride with edetate and reagent for 4 h, and either 0.001% chlorhexidine for 4 h or 0.004% chlorhexidine for 1 h. Thus, for patients who are careless or persist in using nonsterile rinsing solutions, it appears that at least some methods of disinfection will help prevent Acanthamoeba infection. PMID- 2189678 TI - Pseudomonas keratitis and contact lens wear: the lens/eye is at fault. AB - Microbial keratitis with Pseudomonas aeruginosa is the most common corneal infection associated with contact lenses (CLs). Pseudomonas organisms are ubiquitous in nature, and can colonize CLs without a prior breach in lens care or hygiene. Although poor lens care is often found in affected patients, lens contamination and traumatic epithelial defects are more relevant. Hydrophilic lenses, particularly extended wear lenses, have been associated with a greater frequency of Pseudomonas keratitis. The polymer matrix of these lenses is apparently suited to the avid adherence of Pseudomonas organisms. Adherence is promoted by the presence of lens coatings, which begin to accumulate upon lens insertion and whose level mounts over time. Evidence suggests that infection is more common with mucin-coated contaminated CLs than with noncoated contaminated CLs. In general, lens wear can promote bacterial adherence to the ocular surface by shielding the cornea from the wiping action of the eyelids and immune components in tears. Still, experimental models have shown that keratitis develops regularly (84%) only in corneas that have been traumatized. Trauma may arise through lens insertion or removal, deposits or debris entrapment, hypoxia, or toxic reactions to solution preservatives. Extended wear is believed to facilitate the infectious process because of the chronic accumulation of coatings, the chronic exposure of CLs to potentially adherent bacteria, the continuous presence of irritating lens deposits, the prolonged entrapment of debris beneath the lens, and the relative infrequency of lens cleaning and disinfection. PMID- 2189679 TI - How important are lens oxygen ratings? They are one of many performance factors. AB - To prevent corneal edema in most patients, contact lenses must transmit oxygen to the following minimum degree: (a) in daily wear, 24.1 x 10(-9) (cm x ml O2)/(s x ml x mm Hg), and (b) in extended wear, 34.3 x 10(-9) (cm x ml O2)/(s x ml x mm Hg). High Dk/L ratings are particularly important for patients wearing extended wear lenses and for those with exceptionally high corneal oxygen demand. Nevertheless, it is well known that other lens performance properties can be compromised by manipulating material or design parameters to increase the Dk/L rating. Increasing the Dk/L of hydrogel lenses, for example, may lead to problems such as fragility, dehydration, and corneal adherence. Similarly, high-Dk/L, rigid gas-permeable lenses may exhibit poor surface wettability and flexural resistance, base curve radius changes, and possible corneal adherence. Because such problems can compromise visual acuity, affect ease of handling, or decrease comfort, nonoxygen factors may exert a stronger influence on successful lens wear than high oxygen transmissibility alone for most patients. Among the nonoxygen factors important for contact lens wear are good movement, surface wettability, resistance to deposit buildup, and flexural resistance. Clinicians must consider these properties, along with oxygen transmission ratings, when fitting patients with contact lenses. Lenses that exhibit good overall performance, in my view, provide the greatest probability of successful wear. PMID- 2189680 TI - Is your office safe? Yes. AB - Contact lens (CL) fitting carries the risk of transmitting infectious agents, including adenovirus and Pseudomonas. Therefore, a number of precautions must be observed to ensure safety in the office. Paramount among these is hand washing, both immediately after contact with a patient's eyes and again between patients. Equally important is that all trial lenses and CLs removed from patients be disinfected before reuse. Low-water-content soft CLs can be heat disinfected; high-water-content CLs require chemical treatment. A combination of surfactant cleaning with a chlorhexidine-containing agent and hydrogen peroxide disinfection is preferred for rigid lenses to guarantee destruction of human immunodeficiency virus (HIV). The proper use of lens care solutions is also necessary to minimize the risk of their becoming contaminated with pathogenic organisms. Only commercially prepared solutions should be used, preferably in small-volume bottles that are frequently replaced. Preservative-free solutions should be discarded after 1 day's use, whereas preserved solutions may be used for up to 2 weeks. Sterile saline rather than tap water is recommended for rinsing rigid lenses. Finally, part of the clinician's responsibility in running a safe office is to educate patients about these hygienic practices. PMID- 2189681 TI - Is your office safe? No. AB - The practitioner's office can be an unsafe environment for fitting contact lens (CLs), owing to numerous reservoirs of microbial contamination. These include sinks, trial lenses, solutions, lens cases, multidose dropper bottles, and storage trays. Microbes may also be introduced to the eyes via the practitioner's fingers, the patient's lashes or lids, or cosmetic residues on the ocular adnexa. Because sterility is difficult to achieve in an office, CL fitters must accept the more realistic goal of disinfection. Periodic cultures are necessary to monitor the effectiveness of office hygiene and disinfection. Cultures are especially important, considering that the panel of organisms routinely used to test lens care solutions may not reflect those in office settings, which may become resistant to preservatives. It has been shown, for example, that 50% of chlorhexidine-preserved solutions used in offices can become contaminated with Serratia marcescens within 7 days of bottle opening. At present, it appears that contamination is best avoided by using solutions containing 15 ppm of polyaminopropylbiguanide (PAPB). Frequent replacement of solutions, trial lenses, and lens cases may also help to reduce the likelihood of microbial contamination in the office. PMID- 2189682 TI - Is the dry eye contact lens wearer at risk? Yes. AB - Numerous studies have demonstrated that patients with dry eyes have a compromised ocular surface. Furthermore, these patients suffer deficiencies of various surface defense mechanisms, such as tear volume, tear components (lysozyme, lactoferrin, and beta-lysin), the mucin network, cellular exfoliation, and subsurface immune secretions. When such individuals wear contact lenses (CLs), a special set of circumstances arises that increases the risk of ocular infection. The risk is greatest if the lenses are soft and, therefore, provide for little tear exchange beneath their surface. Under such circumstances, limited tear flow allows for a greater buildup of lens deposits and metabolic wastes, while permitting increased tear evaporation from the lens surface. The pathogenesis of infection is attributed to various mechanisms, including decreased tear flow beneath the lens, decreased tear components, stagnation of the mucin network, changes in surface cell exfoliation, and putative changes in the subsurface immune secretory system. Dry eye patients who wear soft CLs also run a greater risk of bacterial conjunctivitis, blepharitis, and sterile corneal infiltrates. PMID- 2189683 TI - Is the dry eye contact lens wearer at risk? Not usually. AB - Individuals with dry eye symptoms cannot be excluded categorically from contact lens (CL) wear. Most patients with dry eye symptoms have a chronic disorder determined by genetics, age-related changes, or anatomic problems that interfere with blinking or the tear film. Furthermore, their symptoms may be exacerbated by drug use, environmental conditions, or the work they do. Although so-called "marginally" dry eyes usually provoke bothersome symptoms, they pose no real danger to ocular health, seldom require medical care, and are not an absolute contraindication to lens wear. Nevertheless, clinicians should conduct the appropriate tests to identify dry eye patients in the prefitting evaluation, so that potential problems in lens wear can be anticipated and addressed. The value of such testing cannot be overstated, as it is often possible to treat the underlying problem and thereby greatly minimize or even eliminate symptoms. This is particularly so when there is a drug, lens, or environmental component to the condition. Helpful approaches in CL wearers include blinking exercises, the use of wetting drops, or a modification of lens parameters (e.g., increased water content, larger diameter, and better edge design). Matching would-be lens wearers to the appropriate CL system is, of course, paramount. PMID- 2189684 TI - The FDA role in contact lens development and safety. AB - The Food and Drug Administration (FDA) exercises a multifaceted role in fulfilling its mission of enforcing the Federal Food, Drug and Cosmetic Act (Act), functioning not only as industry regulator and consumer protector, but also as scientific advisor and consumer educator regarding medical devices, drugs, foods, cosmetics, and veterinary medicine. Medical devices are regulated within the Center for Devices and Radiological Health. Contact lenses are regulated under the authority of the medical device amendments. The Center is responsible for promulgating regulations, publishing guidelines, and developing written guidance in enforcing the Act, and also for guiding manufacturers of medical devices in safe and effective product development. Other components deal with the compliance of manufacturers with the marketing of medical devices within the meaning of the Act, and through labeling requirements of the Act and consumer education and informational activities. As for contact lenses, the process of updating product development regulations and guidelines is an ongoing activity. The most recent version of the Contact Lens Guideline Document, issued in April 1988, contains two major revisions involving preclinical and clinical testing. The first redefines plastics into one materials category, thus reducing testing requirements with respect to animal toxicology studies and other preclinical areas. The second revision restricts clinical testing requirements to allow confirmatory trials in applications for new daily wear lenses. The intention was to maintain the ability of studies to detect major material or design flaws in lenses, thus boosting confidence in their performance while eliminating unnecessary trials.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189685 TI - Perspectives on the future of contact lens wear: summary. AB - Although most contact lens (CL) patients prefer the convenience of extended wear lenses, 85% of consumers worldwide use their lenses on a daily wear basis. This disparity between preference and practice is due largely to the association of extended wear lenses with a high rate of both short- and long-term problems. Up to 26% of hydrogel extended wear patients cease lens wear because of chronic hypoxia or ocular inflammation. Among patients using extended wear rigid gas permeable (RGP) lenses, discomfort causes 18% of all discontinuations. These problems must be addressed and solved before extended wear can truly become a viable option for CL patients. One possible solution is the development of hydrogel materials that have high gas permeability (100 Dk), minimal water loss, and deposit resistance. In the event that such materials are not forthcoming, the use of currently available extended wear lenses on a daily wear, regular replacement basis offers the greatest chance of success for hydrophilic lenses. Finally, the discomfort associated with rigid lenses may be reduced by developing more flexible RGP materials with an optimum design. PMID- 2189686 TI - Are hard lenses superior to soft? Arguments in favor of hard lenses. AB - The overriding consideration in choosing between soft contact lenses (SCLs) and rigid gas-permeable (RGP) lenses is the severity of the changes each induces in the corneal epithelium, endothelium, and conjunctival structures. Lens-related epithelial changes are largely the consequence of relative oxygen deprivation and consequent corneal edema. Factors such as lower oxygen transmissibility, minimal tear exchange capacity, and large diameters may explain why SCL wearers show a higher rate of corneal infiltrates, sterile ulcers, and irregular staining patterns than users of RGP lenses. The greater association of hydrogels with infectious keratitis may reflect their tendency to accumulate proteinaceous deposits, harbor bacteria in the polymer matrix, and resist easy disinfection. SCL wear has been linked to endothelial polymegethism, a largely irreversible condition that may cause more rapid corneal swelling and slower deswelling after periods of hypoxic stress. Among the conjunctival problems more often seen in SCL wearers are superficial neovascularization, contact lens-related superior limbic keratoconjunctivitis, and giant papillary conjunctivitis. Mechanical irritation from large-diameter lenses, a tendency to build up mucoproteinaceous deposits, corneal draping, and hypersensitivity to preservatives in SCL care products may play a role in these problems. PMID- 2189687 TI - Reversal of the limited proteolysis of MP26 during the reversal and prevention of the galactose cataract in rat lenses. AB - The reversal and prevention of the galactose-induced cataract in rats were employed to study their effects on the acceleration of the limited proteolysis of MP26 into MP23-24 previously observed in cataractous lenses of galactose-fed animals. Lenses of rats on a cataract reversal-diet demonstrated the reversal of MP23-24 and MP26 levels to control levels in the clearing cortical areas but not in remaining cataractous nuclear areas. Acceleration of the limited proteolysis of MP26 was observed in the nucleus but not the cortex in the clear lenses of animals on a cataract prevention-diet. The results demonstrated that the limited proteolysis of MP26 may form part of a gradual aging process that although not directly (causally) related to cataractogenesis may at least be accelerated by cataractogenic agents or conditions. PMID- 2189688 TI - Auxiliary production of antibodies to ocular antigens in experimental autoimmune uveoretinitis. AB - In experimental autoimmune uveoretinitis (EAU), there are concurrent autoreactive humoral and cellular immune responses. Many studies have recently focused on T cell reactivities in EAU, while analysis of autoantibody responses to uveitogenic epitopes has been less well characterized. In this study, a defined 16-mer uveitogenic interphotoreceptor retinoid binding protein (IRBP) peptide, designated #896, was used to induce EAU. Histological analysis of eyes at day 10 demonstrated extensive leukocyte infiltration of the anterior segment, with mononuclear and plasma cells in the posterior segment. The presence of plasma cells suggests local production of antibodies within the eye. ELISA analyses of serum, aqueous, and vitreous from rats with IRBP-induced, severe EAU revealed the presence of antibodies against peptide #896. There was little difference between the serum and intraocular antibody titers, presumably due to breakdown of the blood-ocular barriers. In addition to the anti-#896-IRBP antibodies, there were detectable antibodies reactive against separate and distinct IRBP epitopes, as well as, against epitopes on retinal-S antigen. These results indicate that in #896-peptide-induced severe EAU, humoral immune responses are induced to the primary immunogen and that there is also auxiliary production of autoreactive antibodies against other epitopes present on intraocular antigens. These auxiliary responses may contribute to the immunopathogenesis of severe EAU. PMID- 2189689 TI - Adsorptive and fluid phase endocytosis by cultured rabbit corneal endothelium. AB - In addition to maintaining corneal transparency via a pump-leak mechanism, the corneal endothelium plays an active role in the transport of certain proteins to supply nutrients for the stroma and to remove metabolites. In order to investigate transcellular transport mechanisms across the endothelium, we exposed cultured rabbit corneal endothelial cells to tracers that are commonly used to describe various forms of endocytosis. The cells were incubated on their apical surfaces in solutions containing different HRP conjugated lectins (concanavalin A and lens culinaris = alpha-D-mannose, alpha-D-glucose; peanut agglutinin = alpha D-galactose), cationized ferritin (CF), native ferritin (NF), and HRP alone for 5 60 min and processed for EM cytochemistry. At early times, the lectins and CF were seen bound to the apical plasma membrane, thus indicating adsorptive endocytosis. The NF and the lectins in the presence of their competing sugar as well as HRP showed little or no surface binding, thus being markers for fluid phase endocytosis. At later times, large amounts of lectins and CF were located in round, tubular, or U-shaped vesicles of various sizes, large vacuoles, multivesicular bodies, and in other cytoplasmic compartments. Very little or no uptake was observed with NF, or when the lectins were used in presence of their competing sugars. HRP was seen in moderate amounts only in round or oval shaped vesicles. This study suggests that adsorptive endocytic pathways play a major role in transcellular transport through the corneal endothelium, whereas the transport of macro-molecules via fluid phase endocytosis is more limited. In addition, our observations suggest that adsorptive endocytic tracers undergo various intracellular fates and also appear to be transported through the cells at different rates. PMID- 2189690 TI - Expansion, selection and maintenance of memory B-cell clones. PMID- 2189691 TI - The generation of B-cell memory: a working hypothesis. PMID- 2189692 TI - The evolution of B-cell clones. AB - This chapter identifies three forms of B-cell memory: (a) B blasts which characterize the established stage of the follicular response to TD antigens, (b) recirculating memory B cells, and (c) non-recirculating memory B cells of the marginal zones of the spleen and equivalent areas of other secondary lymphoid organs. The follicular B blasts show sustained proliferation driven by small amounts of antigen bound to FDCs. The probable relationships between these cells is summarized diagrammatically in Fig. 4. It is probable that follicular B blasts generate both the recirculating and marginal zone memory cells. The chapter by Gray and Leanderson in this volume cites data which indicate that the recirculating memory pool is not sustained for more than a few weeks in the absence of antigen. Data leading to the same conclusion for marginal zone memory B cells is set out in Sect. 5.1 of this chapter. Marginal zone memory B cells do not appear to move spontaneously to follicles for periodic renewal. They will only leave the marginal zone if a fresh supply of antigen reaches them in that site. Recirculating B cells are able to respond to antigen already held on FDCs. It is not known if they are able to displace B blasts of equivalent affinity for antigen which already occupy antigen-holding sites on FDCs. This could be a mechanism by which B blasts with high antigen affinity produced in one follicle could displace blasts of lower affinity in other follicles. Little is known of the factors which regulate the numbers of marginal zone and recirculating follicular memory B cells. In responses to hapten-protein conjugates, hapten binding cells may approach 10% of marginal zone B cells but comprise well under 1% of recirculating follicular cells. The numbers of these memory cells do not increase if the recirculating pool of lymphocytes is depleted, indicating that the factors which regulate the number of memory B cells are independent of those which regulate the total size of the recirculating B-cell pool. A depleted peripheral B-cell pool can only be fully reconstituted by recruitment of newly produced virgin B cells. Data cited in Sect. 5.2 support the concept that this recruitment is at least partially independent of antigen-driven B-cell proliferation. Consequently, substantial proportions of the peripheral B-cell pools are likely to be either virgin cells or cells which have been recruited by antigen or anti-idiotype without entering cell cycle.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2189693 TI - Pgp-1 (Ly 24) as a marker of murine memory T lymphocytes. PMID- 2189694 TI - Hyperventilation syndrome--hiding behind pseudonyms? PMID- 2189695 TI - Transferrin receptor expression in adenocarcinoma of the lung as a histopathologic indicator of prognosis. AB - Immunohistochemical reactivity with OKT9 (antitransferrin receptor) monoclonal antibody was studied in 58 surgically resected adenocarcinomas of the lung. The cell surface and cytoplasm of the tumor cells were stained in 44 cases (76 percent). The expression of the transferrin receptor (TrfR) in tumor cells was compared with histopathologic prognostic factors, such as TNM factors, degree of histologic differentiation, degree of nuclear atypia, and frequency of mitotic figures. The expression of TrfR showed significant correlation with the degree of histopathologic differentiation (p less than 0.025), degree of nuclear atypia (p less than 0.025), and frequency of mitotic figures (p less than 0.001). However, there was no definite correlation with TNM factors. These results indicate that the expression of the TrfR in pulmonary adenocarcinoma corresponds to the elevated proliferative activity of the tumor cells, and that immunohistochemical reactivity with OKT9 can be used as one of the histopathologic indicators of prognosis of pulmonary adenocarcinoma. PMID- 2189696 TI - Efficacy of pressure support ventilation dependent on extravascular lung water. AB - Continuous positive-pressure ventilation and PSV were compared prospectively in patients at a surgical intensive care unit. All patients suffered from mild to moderate ARI (PaO2/FIO2 of 125 to 350 mm Hg). The patients were randomly assigned to a PSV group (n = 28) or a control group with continued CPPV (n = 27). The usual hemodynamic and oxygenation variables, ITBV, and extravascular lung water (ETV) were assessed before and six hours after switching to PSV. The changes (d) of PaO2/FIO2, RI, and P(A-a)O2 were used for evaluation of the effect of PSV. Significant correlations were found between the ETV(CPPV) and dPaO2/FIO2 (r = 0.672), ETV(CPPV) and dRI (r = 0.722), and ETV(CPPV) and dP(A-a)O2 (r = 0.601), which led to the conclusion that the level of ETV determined the efficacy of PSV. In the subgroup with ETV less than 11 ml/kg (n = 15), PSV significantly improved PaO2/FIO2 (248 to 286 mm Hg), RI (1.55 to 1.22), ITBV (801 to 888 ml/m2), cardiac index (4.21 to 4.76 L/min.m2), stroke index (42.2 to 48.1 ml/m2), and oxygen delivery (735 to 833 ml/min.m2). In the subgroup with ETV greater than 11 ml/kg (n = 13), PSV caused a significant deterioration of PaO2/FIO2, RI, and intrapulmonary shunt. It is concluded that in patients with moderate ARI in whom ETV is almost normal, PSV is superior to CPPV, and the efficacy of PSV is independent of the level of oxygenation during CPPV. PMID- 2189697 TI - Respiratory complications and management of spinal cord injuries. PMID- 2189698 TI - The Nagoya conference on system design and patient-ventilator interactions during pressure support ventilation. PMID- 2189700 TI - Help in fighting the war against drugs. PMID- 2189701 TI - [The Professional Society of German Surgeons. I. Retrospect. The beginning]. PMID- 2189699 TI - Trichotillomania in children and adolescents: review of the literature and case report. AB - Hair pulling is an uncommon behavior for which a standard treatment modality has not yet been established; additionally its prognosis is generally guarded. This article reviews the literature and comments upon the demographic, dermatologic, clinical and psychodynamic features of trichotillomania. The various diagnostic association and the treatment approaches are discussed. A case of trichotillomania is presented and the possible relationship between trichotillomania and anxiety is explored. PMID- 2189702 TI - [Esophageal variceal hemorrhage: therapy concepts and results]. PMID- 2189703 TI - [Treatment of bleeding duodenal and stomach ulcer]. PMID- 2189704 TI - [Lower intestinal hemorrhage]. PMID- 2189705 TI - [Integration of surgical research into the education and continuing education of the surgeon]. PMID- 2189706 TI - [Surgical research from experiences of the clinician]. PMID- 2189707 TI - [Perspectives of experimental surgery]. PMID- 2189708 TI - [Financial planning for surgical research. Project portfolio as an instrument for research planning]. AB - Planning of research funding should assure both volume and continuity of economic support. Funding of new research concepts usually depends largely on the internal budget of the research institution (primary economical resources). More mature projects can be funded by governmental and non-profit (secondary) or industrial sources (tertiary economical resources). In general, a balanced proportion of financial support will assure maximal research independence. The respective funding of a research project should be regarded as extrinsic to the quality of the said project. Portfolio analysis of research projects is introduced as a new means of planning and controlling academic and industrial research. In principle, research projects will be evaluated with regard to the inherent potential of development (e.g. potential impact on clinical or scientific concepts) and the current productivity (e.g. output of results and publications). The 2-dimensional portfolio-matrix will be used to analyse these factors, manifesting both the overall activity of a research unit and the development of new research and funding strategies. In addition, repetitive project-portfolio analyses will enable control of both spending and efficiency in research. The application of the current project-portfolio method is exemplified by an analysis of the research activities of the department of surgery at the university of Basel. To date, project-portfolio analysis is not a mature method: Development of more quantitative portfolio strategies and of multidimensional project-portfolios are proposed. However, project-portfolio analysis is a promising means of planning and controlling research. It should be used and developed further in institutions with a number of concurrent research activities. PMID- 2189709 TI - [Uses and risks of drainage following elective colon resection. A prospective, randomized and controlled clinical study]. AB - The results of a controlled randomized and prospective clinical study including 113 patients from March 1987 until August 1988 showed that prophylactic drainage in elective resection for cancer of the colon was not necessary. 60 patients received a drain, 53 patients were not drained. The drain turned out to be ineffective even concerning its expected function of draining intraabdominal fluid: its diagnostic and therapeutic value failed in clinical practice. The rate of surgical complications--i.e. anastomotic leakage, impaired wound healing and relaparotomy--was significantly higher in the drained group. In elective colon resection the use of a drain as a routine procedure cannot be recommended. PMID- 2189710 TI - [Treatment of femoral hernia in children]. AB - From 1975 to 1988 at the Department of Pediatric Surgery in Graz 20 femoral hernias in 16 children were diagnosed and treated by an operative technique, described by Sauer in 1964. Under this method the femoral canal is closed in level of the femoral ring by a pedicle flap, constructed from the transversalis fascia. All patients underwent follow-up examination and were symptom-free. No relapse occurred. For the development of femoral hernias the previous inguinal hernia repair could be a favored factor. PMID- 2189711 TI - [Unilateral lung transplantation]. AB - For patients with terminal pulmonary fibrosis unilateral lung transplantation offers a new therapeutic option. At the Hannover Medical School 5 patients have been successfully treated by single lung transplantation. In 3 patients a left, and in 2 patients a right lung transplant was performed. One patient required intraoperative support by cardiopulmonary bypass. Bronchial omentopexy was used in all instances. Currently all patients are alive. A marked improvement of pulmonary function parameters was seen in all cases. The patients are all able to lead a normal life. PMID- 2189712 TI - [Pancreaticojejunostomy without entero-entero-anastomosis--blind pancreaticojejunostomy]. PMID- 2189713 TI - [Endorectal sonography of rectal cancer on 2 levels. Initial experiences with the endo-multi-level probe]. PMID- 2189714 TI - [Reflections on the 100th anniversary of the death of Richard von Volkmann in November 1989]. PMID- 2189715 TI - [Epidemiologic survey of migraine in six cities of China]. AB - A door-to-door survey was carried out in six cities of China. A total of 63,195 individuals were sampled during 1983 to determine the prevalence of major neurological disorders including migraine. The survey involved a complete census, together with a pretested interview and brief screening examination with a high level of sensitivity for detecting individuals with migraine. All those with responses suggestive of severe headaches were requested to be examined by a senior neurologist using defined clinical criteria to establish the final diagnosis. Based on 396 prevalent cases of migraine, the crude and age-adjusted (to the 1960) total population of the United States point prevalence rate were 6.3 per 1000, and 5.4 per 1000 respectively. The prevalence among the females was nearly 3.5 times the figure for the males. For individuals above the age of 40, the age-specific prevalence rate declined with increasing age. The survey was followed by a case-control pairs matched by age, sex and geographic regions. A family history with "similar headache" seemed to be a significant risk factor while smoking and alcohol consumption appeared to be other relevant factors associated with the occurrence of migraine were also investigated. It seemed to the authors that the most frequently associated factors were psychological and hormonal factors. PMID- 2189716 TI - [Motoric dominance and psychoses]. PMID- 2189717 TI - [Alexia]. PMID- 2189718 TI - Myeloma. AB - Myeloma is a malignancy of plasma cells that are terminally differentiated B lymphocytes. The clinical spectrum varies from the incidental discovery of a pathologically raised monoclonal immunoglobulin on routine electrophoresis in asymptomatic patients to widespread skeletal involvement with incapacitating bone pain. Symptoms may result from a solitary tumor mass, described as an extramedullary plasmacytoma, in virtually any part of the body. Metabolic abnormalities commonly include hypercalcemia, elevated plasma urate levels, or the development of amyloidosis, all of which may disturb renal function. High paraprotein levels cause hyperviscosity, resulting in generalized debility and varying degrees of disturbed mental function. The natural history is determined by the mass of the tumor coupled with its unique biologic features. Median survival of unselected patients, without effective treatment but once symptoms are evident, is approximately 7 months; this period can be significantly prolonged with appropriate therapy. As a first step, urgent medical management is often necessary, centering on rehydration, correction of hyperviscosity, and reversal of metabolic defects, each of which may improve renal function. Over the longer term, specific antitumor drugs have extended median survival to approximately 30 months, and most regimens include a combination of melphalan and prednisone, with or without other cytotoxic drugs. Alternative forms of treatment include sequential hemibody irradiation, recombinant alpha interferon, and in suitably selected patients, high-dose chemoradiotherapy followed by bone marrow transplantation. The latter approaches offer promising management options and are currently the subject of evaluation in controlled clinical trials. PMID- 2189719 TI - Development of a citric acid aerosol as a smoking cessation aid. AB - The satisfaction derived from smoking depends not only on the pharmacological effects of nicotine but also the sensory stimulation from smoke inhalation, particularly the tracheal 'scratch'. In a previous study, we found that a citric acid aerosol produces a tracheal 'scratch' and provides some of the same satisfaction as cigarette smoke. In the present study, we evaluated a new pocket sized device for delivering a citric acid aerosol and examined some of the important variables for providing a satisfying substitute for cigarettes. In the first experiment, volunteers who smoked at least 10 cigarettes per day compared a citric acid aerosol (either alone or with flavor additives) to a cigarette and a placebo. The addition of cigarette smoke flavor was found to best enhance the satisfaction provided by the citric acid aerosol. In the second experiment, smokers were given compact citric acid inhalers to use throughout 8 h of cigarette deprivation. The degree of satisfaction was highly correlated with the intensity of throat sensation provided by the aerosol. This citric acid aerosol inhaler may provide a useful tool for smokers while trying to quit smoking. PMID- 2189720 TI - [Cocaine and cocaine poisoning. Pharmacology, symptoms and treatment]. PMID- 2189721 TI - Expression in Escherichia coli of the psbO gene encoding the 33 kd protein of the oxygen-evolving complex from spinach. AB - The cDNA for the 33 kd protein from the oxygen-evolving complex of spinach together with the coding region for the hydrophobic C-terminal part of the transit sequence was cloned into the expression plasmid pDS12/33Ex. The 33 kd protein precursor was expressed in Escherichia coli, secreted into the periplasm and correctly processed to the mature 33 kd protein. Thus the hydrophobic domain of the transit sequence, preceded by a methionine and two lysine residues, can function as a bacterial signal peptide. The periplasmic proteins were released from the cells by osmotic shock and the expressed protein was purified by anion exchange chromatography. The protein was identified by SDS-PAGE and Western blotting. N-terminal sequence analysis showed that the cleavage of the signal peptide occurred at the correct position. The expressed protein could be rebound to CaCl2-washed PSII particles and oxygen evolution was restored in equal amounts by the 33 kd protein from both E. coli and spinach. PMID- 2189722 TI - A neuropeptide precursor in cerebellum: proenkephalin exists in subpopulations of both neurons and astrocytes. AB - The adult rat cerebellum has minimal enkephalin immunoreactivity and is devoid of opiate-binding activity. Using novel monoclonal antibodies to the mammalian enkephalin precursor, we describe the immunofluorescent detection of proenkephalin, in the absence of mature enkephalin peptides, in subpopulations of rat cerebellar neurons and astrocytes. In cryostat sections, neurons that express proenkephalin include Golgi cells, macroneurons within deep cerebellar nuclei and a subpopulation of Purkinje cells. Proenkephalin messenger RNA and protein are present in subpopulations of both grey and white matter astrocytes, but not Bergmann glia. In dissociated glial culture, proenkephalin is expressed in process-bearing astrocytes, apparently in association with a subset of intermediate filaments. Proenkephalin within astrocytes is not seen until the second postnatal week and increases through to adulthood. Neuropeptide gene expression adds to the growing range of neuronal-type properties glial cells can display. PMID- 2189723 TI - Peptide binding to HLA-DR1: a peptide with most residues substituted to alanine retains MHC binding. AB - Major histocompatibility complex (MHC) glycoproteins play an important role in the development of an effective immune response. An important MHC function is the ability to bind and present 'processed antigens' (peptides) to T cells. We show here that the purified human class II MHC molecule, HLA-DR1, binds peptides that have been shown to be immunogenic in vivo. Detergent-solubilized HLA-DR1 and a papain-cleaved form of the protein lacking the transmembrane and intracellular regions have similar peptide binding properties. A total of 39 single substitutions were made throughout an HLA-DR1 restricted hemagglutinin epitope and the results determine one amino acid in this peptide which is crucial to binding. Based on this analysis, a synthetic peptide was designed containing two residues from the original hemagglutinin epitope embedded in a chain of polyalanine. This peptide binds to HLA-DR1, indicating that the majority of peptide side chains are not required for high affinity peptide binding. PMID- 2189724 TI - Two distinct and frequently mutated regions of retinoblastoma protein are required for binding to SV40 T antigen. AB - The retinoblastoma susceptibility gene (RB) encodes a phosphoprotein of 110 kd (pp110RB) that forms specific complexes with SV40 T antigen and the transforming proteins of several other DNA tumor viruses. Interaction with RB is thought to contribute to transformation by these viruses as demonstrated by genetic analyses. To help understand the function of these interactions, the regions of RB that are involved in binding to T have been mapped. An in vitro protein synthesis system capable of producing full-length RB protein has been developed to facilitate the mapping study. A 5- to 10-fold increase in translational efficiency in the reticulocyte lysate was obtained when the 5' non-coding region of RB mRNA was replaced with that of beta-globin mRNA or a plant viral RNA, alfalfa mosaic virus (AMV) RNA4. A series of mutated RB polypeptides produced from this system were assayed for T binding. Two non-contiguous regions of the RB protein, amino acid residues 394-571 and 649-773, were found to be necessary for binding to T: mutations in either region abolished T-RB complex formation. These results are consistent with the finding that, in all the cases analyzed so far, mutated RB proteins in human tumor cells also failed to bind to T antigen due to deletions including at least one of the two required regions. Thus the regions of RB defined in vitro as necessary for interaction with T might be physiologically relevant as well, and might play a fundamental role in normal RB protein function. PMID- 2189725 TI - The mechanism of group I self-splicing: an internal guide sequence can be provided in trans. AB - We have reconstituted a group I self-splicing reaction between two RNA molecules with different functional RNA parts: a substrate molecule containing the 5' splice site and a functional internal guide sequence (IGS), and a ribozyme molecule with core structure elements and splice sites but a mutated IGS. The 5' exon of the substrate molecule is ligated in trans to the 3' exon of the ribozyme molecule, suggesting that the deficient IGS in the ribozyme can be replaced by an externally added IGS present on the substrate molecule. This result is different from catalysis mediated by proteins where it is not possible to dissect the specificity of an enzyme from its catalytic activity. PMID- 2189726 TI - How Trp repressor binds to its operator. AB - We propose that the generally accepted model of a single Trp repressor dimer binding to a center of symmetry in the natural trp operator (Otwinowski et al., 1988) is wrong. We show here that the Trp repressor binds to a sequence whose center is located four base pairs either to the right or to the left of the central axis of symmetry that was previously identified. We show that: (i) the oligonucleotide used by Otwinowski et al. is not retarded by the Trp repressor in a mobility shift assay under conditions wherein a shorter oligonucleotide carrying our consensus sequence is retarded, (ii) that methylation protection experiments on the full natural operator sequence and the short oligonucleotide protect similar patterns and (iii) that by varying every base in the shorter oligonucleotide, we can demonstrate an optimal sequence for Trp repressor binding. PMID- 2189727 TI - Drosophila chaoptin, a member of the leucine-rich repeat family, is a photoreceptor cell-specific adhesion molecule. AB - Drosophila chaoptin, required for photoreceptor cell morphogenesis, is a member of the leucine-rich repeat family of proteins. On the basis of biochemical and genetic analyses we previously proposed that chaoptin might function as a cell adhesion molecule. To test this hypothesis, chaoptin cDNA driven by the hsp 70 promoter was transfected into non-self-adherent Drosophila Schneider line 2 (S2) cells. Following heat shock induction of chaoptin expression, the transfected S2 cells formed multicellular aggregates. Mixing experiments of chaoptin expressing and non-expressing cells suggest that chaoptin expressing cells adhere homotypically. Previously it was shown that chaoptin is exclusively localized to photoreceptor cells. Thus, chaoptin is a cell-type-specific adhesion molecule. Biochemical analyses presented in this paper demonstrate that chaoptin is linked to the extracellular surface of the plasma membrane by covalent attachment to glycosyl-phosphatidylinositol. We propose that chaoptin and several other members of the leucine-rich repeat family of proteins define a new class of cell adhesion molecules. PMID- 2189728 TI - Extracellular transport of cholera toxin B subunit using Neisseria IgA protease beta-domain: conformation-dependent outer membrane translocation. AB - The beta-domain of the Neisseria IgA protease precursor (Iga) provides the essential transport function for the protease across the outer membrane. To investigate the secretion function of the beta-domain (Iga beta), we engineered hybrid proteins between Iga beta and the non-toxic 12 kd cholera toxin B subunit (CtxB) and examined their targeting behaviour in Salmonella typhimurium. We show that CtxB-Iga beta hybrid proteins integrate into the outer membrane, leading to the exposition of the CtxB moiety on the cell surface. Exposed CtxB can be degraded by externally added proteases like trypsin, but can also be specifically cleaved off from membrane-associated Iga beta by purified IgA protease. We further demonstrate that folding of the CtxB moiety at the periplasmic side of the outer membrane interferes with its translocation. Prevention of disulphide induced folding in periplasmic CtxB renders the protein moiety competent for outer membrane transport. Iga beta may be of general interest as an export vehicle for even larger proteins from Gram-negative bacteria. PMID- 2189729 TI - Ovarian carcinoma: an ultrasound study. AB - Between March 1986 and March 1989, 65 epithelial ovarian carcinomas were studied by means of real time high resolution ultrasound. The sonographic findings were correlated with FIGO stage, histotype and histological grade. The echostructure was compared with that of a group of 141 benign controls. Moreover, some sonographic patterns, significantly more frequent in the malignant tumors (ascites, irregular borders, peritoneal growths), were identified. The diagnosis of malignancy was as accurate as 90.0%, sensitivity and specificity were 84.7% and 92.3% respectively. Our results, coupled with the low costs involved and the non-invasiveness of the method, thus confirm that ultrasound can still be considered a primary technique in the preoperative assessment of ovarian masses. PMID- 2189730 TI - Ring chromosome 7: report of the fifth case. AB - A 13-year-old boy with a 46,XY,r(7) karyotype presented with growth failure, microcephaly, achromic spots and multiple pigmented naevi. Psychomotor development was normal and no major malformations were present. Comparison with four previously reported patients with ring chromosome 7 shows that the most frequent findings in these subjects were short stature, microcephaly and dermatological abnormalities. PMID- 2189731 TI - Deficiency of the alpha and beta subunits of pyruvate dehydrogenase in a patient with lactic acidosis and unexpected sudden death. AB - An infant with moderate muscular hypotonia and congenital lactic acidosis died suddenly at the age of 3 months. Autopsy revealed no abnormalities responsible for this unexpected death. Measurement of mitochondrial enzymes involved in energy production indicated a severely decreased total pyruvate dehydrogenase complex (PDHC) activity in muscle tissue (0.23 nmoles x min-1 x mg protein-1, control range 2.8-8.7) and moderately decreased PDHC activity in fibroblasts (0.27 nmoles x min-1 x mg protein-1, control range 0.37-2.32). The activity of the first component E1 (pyruvate dehydrogenase) in muscle tissue was 10 times lower than that of controls (0.008 nmoles x min-1 x mg protein-1, control range 0.10-0.25). The activities of dihydrolipoyl dehydrogenase (E3) and various other mitochondrial enzymes were normal. Immunochemical analysis in skeletal muscle tissue and fibroblasts demonstrated a decrease in the amount of the alpha and beta subunits of E1. The features of this patient are compared with those of other patients reported in the literature with immunochemically confirmed combined E1 alpha and beta deficiency. PMID- 2189733 TI - Symmetrical necrosis of the basal ganglia in methylmalonic acidaemia. AB - In a patient with methylmalonic acidaemia (MMAA), persistent neurological symptoms were observed in addition to the acute episodes of metabolic dysequilibrium. CT scan and magnetic resonance imaging revealed bilateral symmetrical necrosis of the globus pallidus. Different episodes of metabolic decompensation, one with severe acidosis, had occurred. Persistent neurological symptoms in patients with MMAA who are appropriately treated suggest irreversible brain damage which appears to occur preferentially at the level of the basal ganglia. PMID- 2189732 TI - Primary hyperoxaluria type I. AB - Primary hyperoxaluria type I is a metabolic disorder caused by the deficiency of the peroxisomal alanine:glyoxylate aminotransferase. The disease is inherited as an autosomal recessive trait. The clinical course is outlined based on data from 330 published cases. Diagnostic cornerstones are clinical parameters, urinary excretion of oxalate and glycolate, and the determination of enzyme activity in liver tissue. Principles of conservative treatment, e.g. volume load and pyridoxine substitution, are described as well as experience with different modes of dialysis and transplantation. Kidney transplantation is associated with a high rate of recurrence of the original disease despite excellent management resulting in many instances in early graft loss. Liver transplantation offers the possibility to correct the metabolic defect and to prevent the progression of crystal deposition in the body. PMID- 2189734 TI - Very early prolonged premature rupture of membranes and survival. AB - Fetal survival is possible even with very premature rupture of membranes followed by persisting oligohydramnios, secondary Potter facies and limb deformities. A case history is given with continuous amniotic fluid loss starting at 11+4 weeks, without development of pulmonary hypoplasia. PMID- 2189735 TI - Regulation of interleukin 1 generation in immune-activated fibroblasts. AB - In the present study we have demonstrated that fibroblasts can generate the inflammatory cytokine interleukin 1 (IL 1) under conditions similar to those abundant in cellular immune responses. Thus, induction of IL 1 requires a sequential two-step protocol which consists of preactivation of mouse embryo fibroblasts (MEF) with crude preparations of T cell or macrophage-derived conditioned media (CM; 72 h), followed by a challenge with lipopolysaccharide (LPS; 24 h). Unstimulated fibroblasts or such cells activated by either CM or LPS produced only low levels of IL 1, while a synergism between both signals was observed for obtaining maximal IL 1-like activity in MEF. Each of a series of individual recombinant lymphokines and cytokines (IL 2, granulocyte/macrophage colony-stimulating factor, tumor necrosis factor, IL 1 beta and interferons alpha, beta and gamma) was shown to serve as an efficient priming signal for the induction of IL 1. IL 1-like activity in fibroblasts was detected in cell lysates or associated with the producing-cell membrane but not in culture fluids. Immune stimulated fibroblasts, activated under such experimental conditions, were shown to actively transcribe mRNA of both IL 1 genes (alpha and beta). For the expression of IL 1-specific mRNA in fibroblasts a single stimulus, provided by either LPS or a lymphokine/cytokine, was sufficient; however, a more intense signal was observed when both stimuli were applied. The IL 1-like biological activity of fibroblast origin was significantly reduced by anti-IL 1 alpha antibodies. Thus, fibroblasts, when activated by immune and bacterial products, generate IL 1 which in turn possibly amplifies cellular immune responses or inflammatory processes in connective tissues. PMID- 2189736 TI - Serological analysis of the dissociation process of HLA-B and C class I molecules. AB - Two forms of HLA class I molecules reacting differentially with the HC-10 monoclonal antibody were identified at the surface of HLA-A3, B7, Cw3 or Cw7 human cells. The HC-10-nonreactive form (which includes all HLA-A3 and a large fraction of HLA-B7, Cw3 and or Cw7 molecules) corresponds to heavy chains apparently tightly associated to beta 2-microglobulin. The HC-10-reactive form (which represents only a fraction of cell surface expressed HLA-B7, Cw3 and Cw7 molecules) corresponds to heavy chains loosely but still associated to beta 2 microglobulin. Further biochemical analyses and the study of mouse transfected cells expressing other HLA class I specificities led to the following conclusions: (a) dissociation of HLA-B and C molecules is a multistep phenomenon, the various stages being identifiable serologically; (b) acquisition of the HC-10 antigenic determinant appears as a hallmark of HLA class I molecules engaged in the process of dissociation; however, its expression does not imply complete separation of heavy and light chains; (c) only the initial stage of the dissociation process can be identified on cell surfaces, whereas (d) following addition of detergent, dissociation of HLA-B and C molecules spontaneously proceeds further, resulting in accumulation in cell lysate of cell surface derived isolated HLA-B and C class I heavy chains. PMID- 2189737 TI - Differential characteristics of the thoracic and abdominal mammary glands from mice. AB - The anatomical and physiological characteristics of thoracic and abdominal mammary glands were investigated in order to understand why the incidence of mammary tumors is higher in the former. Epithelium in explants from both sets of glands required DNA synthesis, insulin, cortisol, and prolactin for full differentiation as measured by alpha-lactalbumin accumulation. The temporal pattern and magnitude of response were the same with respect to both DNA synthesis and differentiation; however, the epithelium in explants from the thoracic glands required concentrations of hormones for alpha-lactalbumin accumulation only one-half to one-third those from abdominal glands. Tumor distribution did not appear to correlate with mammary gland histology, size, or epithelial content. PMID- 2189738 TI - Extracellular glycoproteins at acetylcholine receptor clusters of rat myotubes are organized into domains. AB - Cultured neonatal rat myotubes develop acetylcholine receptor (AChR) clusters where they adhere to the substrate. These clusters are often linear, with AChR rich domains alternating with AChR-poor "contact domains" closer to the tissue culture substrate. We have used sequential detergent extraction and immunofluorescence microscopy to localize extracellular matrix components within these two domains. Laminin, heparan sulfate proteoglycan, type IV collagen, and fibronectin are present at AChR-rich domains; nerve cell adhesion molecule is present at both AChR and contact domains. Extracts of contact domains are enriched in a 36-kDa concanavalin A binding protein and in a 90-kDa polypeptide recognized by antibodies against rat muscle adherons. These results suggest that extracellular components at substrate-apposed AChR clusters are organized into distinct domains that parallel the organization of the cluster bilayer. PMID- 2189739 TI - Differential inhibition of macrophage proliferation by anti-transferrin receptor antibody ER-MP21: correlation to macrophage differentiation stage. AB - Monoclonal antibodies (mAbs) directed against the transferrin receptor are known to inhibit proliferation of cells due to iron deprivation. Some cell types, however, escape from growth inhibition by a mechanism which is unclear at present. This mechanism is the subject of the present study. We investigated the differential growth inhibition caused by anti-transferrin receptor mAb ER-MP21 in connection with the differentiation of murine macrophages (M phi). Therefore, we applied two models of M phi differentiation, namely, culture of bone marrow cells in the presence of M-CSF and a panel of M phi cell lines ordered in a linear differentiation sequence. In both models we observed that proliferation of M phi precursors was strongly inhibited by ER-MP21. In contrast, proliferation of more mature stages of M phi differentiation was hardly affected. Remarkably, iron uptake by M phi precursor and mature M phi cell lines was inhibited by ER-MP21 to the same extent. However, mature M phi cell lines showed an iron uptake two- to threefold higher than that of M phi precursor cell lines. These observations strongly suggest that mature M phi escape from ER-MP21-mediated growth inhibition, because these cells take up more iron than is actually needed for proliferation. Furthermore, we found that enhanced iron uptake by mature M phi is not necessarily accompanied by a higher cell surface expression of transferrin receptors, thus suggesting an increased recycling of transferrin receptors in mature M phi. PMID- 2189740 TI - Long-term culture of rat liver cell spheroids in hormonally defined media. AB - Liver cells of new-born rats, which were found to be able to form spheroidal aggregates when cultured on a nonadherent plastic substratum, were studied under various conditions of culture, mainly by adding different nutrients and growth factors to the culture medium. Analysis of hepatocyte-specific functions was carried out by immunoprecipitation to detect specific proteins newly secreted by liver cell spheroids on different days of culture. When no supplement was added to culture medium, the secretion of albumin and transferrin by liver cell spheroids was no longer detectable after 2 weeks of culture. When dexamethasone, glucagon, insulin, and EGF were added to culture medium, the secretion of albumin and transferrin remained detectable at least until 60 days of culture. This was even more striking when trace elements were added in addition to the three hormones and EGF. The effects of addition of these various factors to culture medium were also detectable with respect to alpha-FP secretion. Even after 54 days of culture in total supplemented medium, these liver cell spheroids could be transferred on a collagen-coated plastic substratum to form a monolayer of uniform liver parenchyma-like cells. The presence of extracellular matrix-like material was observed on the surface of cell spheroids. This could be responsible for attachment and fusion between cell spheroids. Thus, liver cell spheroids cultured in total supplemented medium ensured cell attachment to a biological matrix and cell-cell contact, which is thought to help maintain cell differentiation. Liver cell spheroids offer the possibility of toxicological and pharmacological studies as well as cultures in biomatrix and coculture systems. In addition these liver cells can be used for experiments in liver cell transplantation. PMID- 2189741 TI - A field study of the survival of Legionella pneumophila in a hospital hot-water system. AB - The colonization, survival and control of Legionella pneumophila in a hospital hot-water system was examined. The organism was consistently isolated from calorifier drain-water samples at temperatures of 50 degrees C or below, despite previous chlorination of the system. When the temperature of one of two linked calorifiers was raised to 60 degrees C, by closing off the cold-water feed, the legionella count decreased from c. 10(4) c.f.u./l to an undetectable level. However, 10 min after turning on the cold-water feed which produced a fall in calorifier temperature, the count in the calorifier drain water returned to its original level. Investigations revealed that the cold-water supply was continually feeding the calorifiers with L. pneumophila. Simple modifications in the design of the system were made so that the cold-water feed no longer exceeds 20 degrees C; these measures have considerably reduced the number of L. pneumophila reaching the calorifiers. PMID- 2189742 TI - Application of a new phagetyping scheme to campylobacters isolated during outbreaks. AB - A new scheme for phagetyping campylobacters has been evaluated using strains isolated from five outbreaks. The phagetyping results have been compared with the results of Penner serotyping, Lior serotyping and Preston biotyping. Phagetyping recognized the causative strains in all of the incidents and also differentiated these strains from animal and environmental strains isolated during these investigations. In some outbreaks phagetyping proved to be more discriminatory than serotyping or biotyping, e.g. strains of Penner serotype 2, and serogroup 4, 13, 16, 50 were subdivided by this method. Phagetyping is to be recommended for typing strains from outbreaks and although the results indicate that it may be used alone we advocate that it should be used in conjunction with one of the established typing methods. PMID- 2189743 TI - Reduction in faecal excretion of Salmonella typhimurium strain F98 in chickens vaccinated with live and killed S. typhimurium organisms. AB - Chickens given orally at 4 days of age a smooth spectinomycin resistant mutant (Spcr) of Salmonella typhimurium strain F98 excreted the organism in their faeces for approximately 4 weeks. Following oral administration of a nalidixic acid resistant (Nalr) mutant of the same strain 4 weeks later when the chickens had virtually cleared themselves of the first infection, these chickens excreted far fewer salmonella organisms and for a shorter time than did a previously uninfected control group of chickens which were infected at the same time with the Nalr mutant. Chickens inoculated intramuscularly at 4 days developed a similar immunity to challenge and also excreted the immunizing strain in their faeces. In contrast intramuscular inoculation or incorporation into the food of formalin-killed S. typhimurium organisms had little lasting effect on the faecal excretion of the challenge strain. Two attenuated mutants of strain F98 Nalr were produced: one was a rough strain produced by lytic bacteriophage and the other was an aro A auxotrophic mutant which had been cured of the 85 kilobase-pair virulence-associated plasmid. These mutants were avirulent for chickens, mice, calves and man and when ingested by human volunteers did not persist in the faeces. When inoculated intramuscularly into chickens they produced an early reduction in faecal excretion of the challenge strain (Spcr) which was not maintained. Oral administration of both strains produced reductions in faecal excretion of the challenge strain. This was much more noticeable with the rough strain which was itself excreted for a much longer period than the parent strain. PMID- 2189744 TI - Comparison of SDS-PAGE protein patterns with other typing methods for investigating the epidemiology of 'Klebsiella aerogenes'. AB - Twenty-four cultures comprising 20 clinical isolates of 'Klebsiella aerogenes' from two hospitals, a reference strain of 'K. aerogenes' and the type strains of three other Klebsiella species, were characterized by one-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of whole-cell proteins. The protein patterns were highly reproducible and were used as the basis of a numerical analysis which divided the clinical isolates into 12 protein types. Comparison with established typing methods indicated that the level of discrimination of SDS-PAGE was similar to that achieved with conventional typing methods but the strains were grouped differently. Protein typing subdivided five serotype K3 isolates that could also be distinguished by phage typing. Conversely, three strains of protein type 11 were clearly distinguishable by both serotyping and phage typing. We conclude that high-resolution SDS-PAGE of proteins provides an effective adjunct to other methods for typing isolates of 'K. aerogenes'. PMID- 2189745 TI - Notice of retraction. PMID- 2189747 TI - Critical period for induction of congenital hydrocephalus and dysplasia of subcommissural organ by prenatal X-irradiation in rats. AB - A single whole-body X-irradiation of pregnant Wistar rats at a dose of 1.05 Gy at 10.30, 12.30 and 14.30 h respectively, of gestational day 10 resulted in significantly high incidences of hydrocephalic offspring. No hydrocephalic offspring resulted from X-irradiation of pregnant rats with 1.05 Gy at 16.30 h, whereas a dose of 1.22 Gy at 16.30 h resulted in a low but statistically significant incidence of hydrocephalus. Neither 1.05 Gy nor 1.22 Gy X-irradiation of pregnant rats at 18.30 h resulted in any hydrocephalic offspring. Dysplasia of the subcommissural organ was noticed in all the hydrocephalic brains histologically examined. PMID- 2189746 TI - Sialic acid binding lectins. AB - The literature contains several reviews on lectins in general, covering mainly those from plants and invertebrates. However, the sialic acid binding lectins have not been reviewed so far. Considering the importance of sialic acids in cell sociology, lectins which specifically recognize terminal sialic acid residues are potentially useful as analytical tools in studying the biological functions of sialoglycoconjugates. These lectins, along with monoclonal antibodies raised against sialoglycoconjugates, have been used in the detection, affinity purification, cytochemical localization and quantitation of such glycoconjugates. In this review the main emphasis has been placed on the occurrence, general purification procedures, macromolecular properties, sugar specificities and applications of these lectins. PMID- 2189748 TI - Serum thymic factor as a radioprotective agent promoting survival after X irradiation. AB - Serum thymic factor (FTS, zinc-free thymulin) protected mice from death after whole-body X-irradiation. It was significantly radioprotective even when administered after irradiation, but it was more effective when administered both before and after irradiation. The protective effect appears to be due to the enhancement of hematologic recovery in the animals. PMID- 2189749 TI - Effects of isoxazolyl-naphthoquinoneimines on growth and oxygen radical production in Trypanosoma cruzi and Crithidia fasciculata. AB - Several 4-(aminomethylisoxazolyl)-1,2-naphthoquinones inhibited growth and DNA synthesis in Trypanosoma cruzi and stimulated O2 uptake and O2-. generation by the parasite epimastigotes and their mitochondrial and microsomal membranes; these results support the idea that oxygen radicals play a role in quinone toxicity. Maximal effects on respiration and O2-. generation were observed with antimycin-inhibited cells. Similar results as well as stimulation of H2O2 production were obtained with Crithidia fasciculata despite the presence of catalase in this organism. PMID- 2189750 TI - Contraceptive failure of the ovulation method of periodic abstinence. AB - Previously published estimates of probabilities of method and user failure for all contraceptive methods suffer from a serious methodological error and are biased downward, with the extent of bias unknown. Data from a World Health Organization clinical trial of the ovulation method of periodic abstinence were used to provide the first correctly calculated measures of method and user efficacy and to determine the characteristics that distinguish women who consciously take risks from those who do not. Probabilities of pregnancy during the first year are 3.1 percent during perfect use (method failure) and 86.4 percent during imperfect use (user failure). Thus, if used perfectly, the ovulation method is very effective. However, it is extremely unforgiving of imperfect use. Because perfect compliance is difficult for many couples who desire intercourse when it is forbidden by ovulation method rules, and because the risk of pregnancy during imperfect use is so great, the ovulation method cannot be considered an ideal contraceptive method for the typical couple, who are likely to be less compliant than couples who volunteer for a clinical trial. The probability of an accidental pregnancy is greatest when any of the three most serious rules--no intercourse during mucus days, within three days after the day of peak fecundity or during times of stress--are broken. Those who have a poor attitude toward the rules are more likely to take risks, including serious risks. Those who get away with taking a risk (i.e., do not get pregnant) are very likely to take risks again. Because breaking the most serious rules entails a 28 percent risk of pregnancy per cycle, those likely to take risks should be counseled about the probable consequences. PMID- 2189751 TI - The future of adjuvant treatment in gastrointestinal cancer. AB - Adjuvant treatment is based on the concept that surgery is only potentially curative and that apparently localized disease has extended beyond surgical resection or is already disseminated. Although death might be related to local recurrence as well as to disease dissemination, most of the trials have tested only one adjuvant modality. Among many negative and non-contributory studies, very few positive results were obtained: in rectal cancer it seems that pre operative and perhaps postoperative radiotherapy may reduce the incidence of local recurrences, and in colon cancer patients treated with Methyl-CCNU, vincristine and 5-fluorouracil (5-FU) had a significant increase in survival. In colon cancer, the lack of active drug might at least partly explain negative studies, but in gastric cancer the most active combination in advanced disease has failed to demonstrate an improvement of survival in the adjuvant setting. Future trials should take account of this succession of negative trials. PMID- 2189752 TI - Fat necrosis of the breast: an unusual complication of lumpectomy and radiotherapy in breast cancer. Review of literature and report of four new cases. AB - Fat necrosis of the breast following excision and radiotherapy in early breast cancer is a newly recognised complication. Further to the nine cases reported so far, another four cases are described. Clinically it is difficult to differentiate between areas of local recurrence and fat necrosis. Therefore, the diagnosis must be only made on histological material. The aetiology, incidence and treatment of this condition is discussed. PMID- 2189753 TI - Ethical considerations of the new reproductive technologies. Ethics Committee of The American Fertility Society. AB - In September 1986, The American Fertility Society issued a report, Ethical Considerations of the New Reproductive Technologies, setting forth the then-held ethical position of the Society on the various new reproductive technologies. In 1987, the Congregation for the Doctrine of the Faith issued the Instruction on the Respect for Human Life and Its Origin and on the Dignity of Procreation. While both documents state that very similar moral criteria were used to derive ethical positions with respect to various reproductive procedures, the conclusions as to the ethical acceptability of the various procedures differ sharply in the two documents. The question can be raised about the procedure used by the Congregation of the Faith to derive its conclusions from the stated premises. Thus, while stating that "the individual integrally and adequately considered" is to be the basis of the moral judgment, the fact is that most conclusions are based on and referenced to past Catholic statements. While the difference in conclusion from similar premises may be troubling to society, it can be especially paralyzing to four groups: (1) those who face problems that might be solved by one or another of the new reproductive technologies; (2) those who are involved in applying them; (3) those who are responsible for institutional policies where such techniques may be applied; and (4) those who are in a position to influence public policy in a legislative or regulatory way. Because of the conflicting conclusions of the two documents, the present Ethics Committee (1986-87) of The American Fertility Society was convened and considered these guidelines in the light of the Instruction. For reasons set forth previously, the Committee reaffirmed the finding of the 1985-86 Committee that basic in vitro fertilization with homologous gametes is ethically acceptable. The Committee reaffirmed the finding that the use of heterologous gametes is also ethically acceptable, provided that various precautions and guidelines are observed, as outlined in its previous report. The Committee recognized and re evaluated the long-debated and very complex issue of the moral status of the gamete, zygote, pre-embryo, embryo, and fetus. The reasons for believing that progressive degrees of respect are due with progressive development were set forth here and in the previous document. The Committee reaffirmed the position that experimentation on the pre-embryo in conformity with the policies and guidelines, as previously expressed, can be ethically justifiable and, indeed, necessary, if the human condition is to be improved.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2189754 TI - [Studies on the pathogenesis of type I diabetes mellitus--destruction of pancreatic beta cells by cytotoxic T lymphocytes in nonobese diabetic mice]. AB - Proliferation of islet-associated leukocytes occurred when isolated islets from 20 week-old female Non-obese Diabetic (NOD) mice were cultured with 10 U/ml recombinant interleukin-2 (rIL-2) for 7 days. Co-culture of these lymphocytes with freshly-isolated islets from 6-8 week-old NOD donors in the presence of 1 U/ml rIL-2 produced islet structural deformation within 24 h and islet cytolysis within 48 h. Three lines of evidence suggest that leukocytes were cytotoxic T lymphocytes (CTL) specific for islet cells. First, these proliferating cells adhered to NOD islets at 6 h and specifically killed islets after 48 h of culture, but the cytoadherence of these cells to the other organs including thyroid, pancreatic exocrine glands and liver from NOD mice could not be observed and the shape of tissue clumps hardly deformed after culture for 48 h. The accumulated insulin release from NOD islets to the medium after 6 h of culture was significantly increased in the presence of islet-derived cells compared with the insulin release in the absence of cells. On the contrary, lactic dehydrogenase activity released from liver and amylase activity from pancreatic exocrine glands showed on difference between with and without these cells for 6h of culture. Second, a flow cytometric analysis showed that these cells consisted of 96%Thy1.2, 70%Lyt2, and 8%L3T4-positive cells. After treatment with monoclonal anti-Thy1.2 or Lyt2 antibody and complement, these cells lost their activity to destroy NOD islets. However, these cells still had a full killing activity after the depletion of L3T4-positive cells. Third, islets of NOD (H-2 genotype KdDb), B10.GD (H-2KdDb), BALB/cA (H-2d), and DBA/2N (H-2d) were susceptible to destructive activity of these cells, whereas islets of NON (H-2b), C57BL/6N (H 2b), C57BL/10J (H-2b), and C3H/He (H-2k) mice remained intact. Furthermore, anti Kd monoclonal antibody could prevent islet-specific cytolysis of these cells. These results suggest that CTL expressing Thy1.2 and Lyt2 phenotypes appear to recognize islet cell antigen with restriction of major histocompatibility complex (MHC) class H-2Kd and then destroy pancreatic beta cells in NOD mice. PMID- 2189755 TI - Thallium in biochemistry. PMID- 2189756 TI - Purification and characterization of native and proteolytic forms of rabbit liver phosphorylase kinase. AB - 1. Two forms of phosphorylase kinase having mol. wt of 1,260,000 (form I) and 205,000 (form II) have been identified by gel filtration chromatography of rabbit liver crude extracts. 2. Form I was the majority when the homogenization buffer was supplemented with a mixture of proteinase inhibitors. This form has been purified through a protocol including ultracentrifugation, gel filtration and affinity chromatography on Sepharose-heparin. 3. Form II was purified by a combination of chromatographic procedures including ion exchange, gel filtration and affinity chromatography on Sepharose-Blue Dextran and Sepharose-histone. 4. Upon electrophoresis in the presence of sodium dodecyl sulfate two subunits of 69,000 and 44,000 were identified for this low molecular weight enzyme. Thus, a tetrameric structure comprising two subunits of each kind can be proposed. 5. Treatment of form I with either trypsin or chymotrypsin gave an active fragment having a molecular weight similar to that of form II. On the contrary, other dissociating treatments with salts, thiols and detergents failed in producing forms of lower molecular weight. 6. The similarities between proteolyzed forms I and II were stressed by their behavior in front of antibodies raised against the muscle isoenzyme of phosphorylase kinase. 7. The study of the effect of magnesium and fluoride ions on the activity of both forms showed an inhibitory effect of magnesium when its concentration exceeded that of ATP. 8. The inhibition could nevertheless be reverted by including 50 mM NaF in the reaction mixture. 9. Form I and form II could be distinguished by their pH dependence in the presence of an excess of magnesium ions over ATP, whereas the affinity for both substrates was not significantly different. PMID- 2189757 TI - The regulatory effects of macrophages on colony stimulating factor-1 (CSF-1) production. AB - 1. By using the anti-sense oligodeoxynucleotide inhibition strategy, we demonstrated that the production of CSF-1 by macrophage was blocked specifically by a CSF-1 anti-sense oligodeoxynucleotide complementary to the 5' end of the coding region of mouse CSF-1 m-RNA transcripts, but not by the CSF-1 mRNA transcripts, but not by the CSF-1 sense oligomer. 2. The LPS-induced condition medium of macrophages treated with CSF-1 anti-sense oligodeoxynucleotide retained the capacity of stimulating mouse fibroblast cells and bone marrow cells producing CSF-1 in vitro. 3. In addition to the inhibition of CSF-1 production by macrophages CSF-1 anti-sense oligodeoxynucleotide also inhibited the CSF-1 production of fibroblast cells and bone marrow cells stimulated by the macrophages conditioned medium. 4. These results suggest that macrophages stimulate their own development by mediating CSF-1 production at least in three ways: (1) production CSF-1; (2) stimulating fibroblast cells; (3) bone marrow cells to produce CSF-1. There is a positive feedback mechanism for macrophage hematopoiesis and its functional expression. PMID- 2189759 TI - Glucokinase as glucose sensor and metabolic signal generator in pancreatic beta cells and hepatocytes. AB - This article reviews evidence for a pivotal role of glucokinase as glucose sensor of the pancreatic beta-cells. Glucokinase explains the capacity, hexose specificity, affinities, sigmoidicity, and anomeric preference of pancreatic islet glycolysis, and because stimulation of glucose metabolism is a prerequisite of glucose stimulation of insulin release, glucokinase also explains many characteristics of this beta-cell function. Glucokinase of the beta-cell is induced or activated by glucose in contrast to liver glucokinase, which is regulated by insulin. Tissue-specific regulation corresponds with observations that liver and pancreatic beta-cell glucokinase are structurally distinct. Glucokinase could play a glucose-sensor role in hepatocytes as well, and certain forms of diabetes mellitus might be due to glucokinase deficiencies in pancreatic beta-cells, hepatocytes, or both. PMID- 2189758 TI - Artificial reversion of acute myeloid leukemia cells into normal phenotype. AB - 1. Induction of tumor cell differentiation could reverse transformed cells into normal, mature cells. Important question is whether these malignant-to-normal reversed cells are really normal ones. 2. We have developed an experimental model based on the examination of three different levels of human acute myeloid leukemia cell properties before and after induction of differentiation: morphological (percentage of undifferentiated blast cells), functional (DNA ploidy, Fc receptors, phagocytic activity, clonogenic assay in soft agar, oxidative metabolism which accompanies phagocytosis in mature granulocytes) and genetical (expression of oncogene p53). 3. Several inducers have been employed: dimethylsulfoxide (DMSO) granulocyte-macrophage colony stimulating factor (GM CSF); tunicamycin, interferon gamma, tumor necrosis factor and lipopolysaccharide. 4. Our results indicate that the reversion of leukemic cells into mature normal ones with some inducers (DMSO, GM-CSF) could be a complete process. PMID- 2189760 TI - Persistence of serum antibodies to 64,000-Mr islet cell protein after onset of type I diabetes. AB - Antibodies to an islet protein of 64,000 Mr (64K antibodies) were measured in 15 diabetic children who were followed prospectively for up to 3 yr after onset of type I (insulin-dependent) diabetes. Of the 15 children, 12 were positive for 64K antibodies at diagnosis. Those patients who were negative for these antibodies at onset remained negative throughout the study. Modest increases in 64K antibodies were observed in 7 patients within 1 mo of diabetes onset, concomitant with an increase in C-peptide concentrations. All antibody-positive patients were still positive at the end of the study, with no significant decrease in antibody levels relative to those at diagnosis, whereas C-peptide concentrations decreased between 3 and 24 mo after onset. Islet cell antibodies, measured by immunochemical staining on sections of rat pancreas, were detected in 9 of 15 patients at onset, whereas only 3 of 11 patients were still positive after 3 yr. In an additional group of 11 patients with diabetes for 6-7 yr, when basal and stimulated C-peptide concentrations were undetectable, 4 patients were still positive for 64K antibodies. These results demonstrate that levels of 64K antibodies persist during the first 3 yr of diabetes, despite declining beta-cell function and decreased immune responses to other islet antigens, but decrease during the next 3-4 yr as the remaining functional beta-cells disappear. PMID- 2189761 TI - Dependence of antigen expression on functional state of beta-cells. AB - Antigen expression corresponding to anti-islet cell surface monoclonal antibodies IC2 and A2B5 was studied. IC2 is a rat-rat hybridoma autoantibody produced from the BB rat; among islet cells, IC2 is beta-cell specific. A2B5 is an anti ganglioside antibody described as labeling beta-cells. Islets of Langerhans from Lewis rats were isolated and cultured for 18 h in RPMI-1640 with five different glucose concentrations (2.2, 3.3, 5.5, 11.1, and 18.3 mM). In some experiments, islets were precultured for 2 or 3 days. After isolation of islet cells and antibody labeling, the percent of IC2+ beta-cells in the different groups increased from 33.3, 34.5, 40.9, and 57.2 to 58.6% (P less than 10(-6). For A2B5, the percent of labeled islet cells increased from 37.4, 41.8, 46.7, and 53.8 to 56.2% (P less than 10(-4). Thus, increasing glucose concentration leading to higher beta-cell activity implies an increase in antigen expression. Neither A2B5 nor IC2 reacts with insulin, as shown by absorption experiments and immune electron microscopy of binding sites. Electron microscopy of IC2-gold-labeled islet cells substantiated the beta-cell specificity of IC2. In conclusion, expression of the corresponding antigens to IC2 and A2B5 depends on the functional state of the beta-cells; because this has been shown to be an important factor in the development of insulin-dependent diabetes, our findings may be of potential pathogenetic interest. PMID- 2189762 TI - Biphasic insulin secretion after intravenous but not after intraportal CCK-8 infusion in rats. AB - The effects of physiological doses of sulfated cholecystokinin-8 (CCK-8) on insulin secretion were investigated in unrestrained unanesthetized rats. The routes of administration were intravenous or intraportal infusion. Intravenous infusion (0.33-5.0 micrograms CCK-8.kg-1.20 min-1) resulted in a biphasic response pattern consisting of a fast 1st-min rise in plasma insulin concentration and a slower second phase that lasted throughout the infusion. The first phase showed the same amplitude with all amounts of CCK-8 administered in this study, whereas the second phase exhibited dose dependency. Blood glucose levels were lowered during all infusions of CCK-8, although the second phase of insulin release was absent with the lowest dose. These results suggest a strong stimulatory effect of CCK-8 on the pancreatic beta-cells, probably by changing the set point for glucose. The described effects of intravenous administration of CCK-8 cannot be produced when the infusion is given into the portal vein. Only very high concentrations of CCK-8 (15 micrograms.kg-1.20 min-1) produced a small increase in plasma insulin levels, indicating a strong CCK-8-eliminating mechanism in the liver. These results indicate that 1) CCK-8 evokes biphasic insulin release and a concomitant drop in glucose levels, and 2) CCK-8 acting on the beta-cell in vivo is not of intestinal origin but is probably released by the pancreatic vagal branch. PMID- 2189763 TI - Lack of systematically found insulin autoantibodies in spontaneously diabetic BB rats. AB - Insulin autoantibodies (IAAs) occur in newly diagnosed human insulin-dependent diabetes mellitus (IDDM) patients, but their presence in BB rats is controversial, possibly due to assay differences or variability in the animals studied. To resolve this controversy, IAAs were measured in well-characterized inbred BB rats both in radioligand assays with 125I-labeled rat insulin I or II, respectively, and in an enzyme-linked immunosorbent assay (ELISA) with rat insulin as antigen. In prospective studies, a total of 57 serums from 16 diabetes prone (DP) BB rats were obtained during an interval ranging from 15 wk to the last week before onset and at onset of diabetes. At comparable ages, 21 serums were obtained from 8 DP BB rats not developing diabetes, and 70 matched serums were obtained from 19 diabetes-resistant (DR) BB rats. Levels of antibody binding increased slightly with increasing age in DP and matched DR rats. Two rats were positive at onset of IDDM in all assays but not in earlier samples. Otherwise, only few isolated serums from both types of rats regardless of diabetes had increased binding in one of the assays. In a cross-sectional study, the insulin binding levels in 150-day-old DP rats (n = 20) that had not yet developed diabetes did not correlate with insulitis present in 3 of 20 rats and did not differ from 150-day-old DR BB rats (n = 20).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189764 TI - Persistent cutaneous insulin allergy resulting from high-molecular-weight insulin aggregates. AB - Cutaneous insulin allergy remains a clinical problem despite the use of highly purified human insulins. We used in vitro lymphocyte-transformation studies to examine the reactivity of various insulin formulations in diabetic patients with (n = 4) and without (n = 8) cutaneous allergies. Nonspecific response to concanavalin A demonstrated a greater than 40-fold response in both groups. Control patients did not respond to the addition of commercial insulin preparations (stimulation index [SI] less than 4), whereas allergic patients had an 11-fold response to beef (P less than 0.01), a 10-fold response to pork (P less than 0.01), and a 6-fold response to human (P less than 0.01) insulins. This response was limited to a single insulin manufacturer's preparations and was uniform in all three species tested. Efforts to identify the offending agent revealed no lymphoblast transformation when crystalline insulin was used or when commercial preparations were purified to a single peak by high-performance liquid chromatography (HPLC). Pure crystalline insulin dimers of beef, pork, and human species were tested; control subjects responded with mean SIs of 1.9, 1.9, and 1.8, respectively, whereas allergic patients showed greater reactivity to beef (SI 7.3) and pork (SI 14.8). The lymphoblast-transformation response to crystalline human dimer was dose dependent with mean SIs of 0.9 at low concentration (2.8 ng/ml) and 19.2 at a higher concentration (20.4 ng/ml). The commercial insulin preparations were run on size-exclusion HPLC to determine high molecular-weight aggregate content. Independent of species, a single manufacturer had products demonstrating aggregate levels 3- to 6-fold higher than those found in other manufacturers' preparations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189765 TI - Inheritance of diabetes mellitus as consequence of gestational hyperglycemia in rats. AB - Our study investigated whether a deterioration of glucose homeostasis and insulin secretion in adult female rats from hyperglycemic dams could be transmitted to the next generation independent of genetic interferences. Dams (F0) were rendered hyperglycemic by continuous glucose infusion during the last week of pregnancy. Females born of these rats (F1) exhibited glucose intolerance and impaired insulin secretion in vivo at adulthood. When they were 3 mo old, they were matched with males born of control dams. During pregnancy, their glucose tolerance remained impaired compared with that of controls. Consequently, F2 newborns of F1 hyperglycemic dams showed the main features of newborns from diabetic mothers: they were hyperglycemic, hyperinsulinemic, and macrosomic. As adults, they displayed basal hyperglycemia and defective glucose tolerance and insulin secretion. This indicates that the long-range deteriorating effects on glucose homeostasis of gestational hyperglycemia in the F1 generation are transmitted to the F2 generation and suggests that a perturbed fetal metabolic environment contributes to the inheritance of diabetes mellitus. PMID- 2189766 TI - Heart transplantation in mildly diabetic patients. AB - From 1985 to 1989, 67 heart transplantations were performed in our hospital, 6 of them in non-insulin-dependent (type II) diabetic patients. Six pretransplantation type II diabetic male heart recipients (mean +/- SD age 50.0 +/- 7.3 yr) were compared with 61 nondiabetic recipients (mean age 44.5 +/- 11.0 yr; 55 men, 6 women) to define whether a different posttransplantation prognosis may be caused by pretransplantation diabetes. Before transplantation, all diabetic recipients (3 newly diagnosed and 3 with diabetes duration of 5, 6, and 12 yr, respectively) were in good glycemic control (mean fasting blood glucose 7.95 +/- 1.62 mM, mean HbA1c 7.6 +/- 0.2%). None had ocular or renal microangiopathic complications, 5 were treated only with diet, and 1 was treated with oral hypoglycemic agents. All recipients were treated with the same immunosuppressive protocol (cyclosporin, prednisone, and since 1986, azathioprine and antilymphocyte globulin), and mean dose and blood levels of cyclosporin were not significantly different between diabetic and nondiabetic recipients. After heart transplantation (mean follow-up 558 +/- 340 days in diabetic and 379 +/- 338 in nondiabetic recipients), the mortality rate and complications (i.e., rejection episodes, supplementary immunosuppressive treatments, major and minor infections, arterial hypertension, and graft atherosclerosis) showed no significant differences except for the more frequent arterial hypertension in diabetic recipients (P less than 0.05), although pretransplantation incidence of hypertension was lower in diabetic candidates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189767 TI - Gut exchange of glucose and lactate in basal state and after oral glucose ingestion in postoperative patients. AB - Glucose uptake by the intestine and its conversion into 3-carbon compounds in the human intestine in the basal state and after an oral glucose load are not understood. Consequently, we studied the arterial and portal venous concentration differences (A-PV) for glucose and glucogenic substrates in the basal state and 3 h after the ingestion of a 100-g glucose load with the catheter technique. Five patients were studied 3-11 days after surgery for gallbladder disease or cancer of the colon or liver. A-PV for glucose in the basal state was 0.12 +/- 0.02 mM (P less than 0.01), indicating net glucose uptake by extrahepatic splanchnic tissues. No net exchange of lactate or pyruvate was detected, but there was release of alanine and uptake of glutamine. After glucose ingestion, glucose was released by the gut, reflecting absorption of the load (mean A-PV for glucose 2.10 +/- 0.04 mM, P less than 0.01). The arterial glucose concentration rose gradually from 4.6 +/- 0.1 mM before glucose ingestion to a plateau at 9.5 +/- 0.7 mM from 90 to 180 min. Glucose ingestion was accompanied by net lactate and alanine release (A-PV -0.16 +/- 0.06 mM and -48 +/- 7 microM, respectively), whereas A-PV for pyruvate did not change. We conclude that, in postoperative patients, there is a significant net glucose uptake by the gastrointestinal tract in the basal state. Glucose ingestion is accompanied by a small release of lactate and alanine from the intestine. However, the estimated net gut formation of lactate and alanine can play only a minor role in the disposal of an oral glucose load. PMID- 2189768 TI - Effects of meal ingestion on plasma amylin concentration in NIDDM and nondiabetic humans. AB - Recent interest has focused on the potential role of amylin in the pathogenesis of non-insulin-dependent diabetes mellitus (NIDDM). This 37-amino acid peptide is found in extracellular amyloid deposits in approximately 50% of pancreatic islets of patients with NIDDM and has been shown to inhibit skeletal muscle glycogen synthesis in vitro. Immunocytochemical studies have colocalized amylin and insulin within beta-cell secretory granules in nondiabetic humans, provoking the following questions. Is amylin cosecreted with insulin? Are circulating amylin concentrations higher in patients with NIDDM either before or after food ingestion? To answer these questions, we developed a sensitive and specific immunoassay to measure plasma concentrations of amylin in humans. Use of this assay indicated that, in lean nondiabetic subjects, glucose ingestion resulted in an increase (P less than 0.001) in the plasma concentration of amylin (from 2.03 +/- 0.22 to 3.78 +/- 0.39 pM) and insulin (from 48.3 +/- 3.1 to 265 +/- 44 pM). There was a significant correlation between the concentrations of insulin and amylin (r = 0.74, P less than 0.001) and the increase in insulin and amylin concentration (r = 0.65, P less than 0.005). Fasting concentrations of amylin did not differ in diabetic and weight-matched nondiabetic subjects and showed a similar pattern of change after ingestion of a mixed meal. We conclude that amylin is secreted in response to ingestion of either glucose or a mixed meal and circulates at concentrations that do not differ in patients with NIDDM and nondiabetic subjects. It remains to be determined whether amylin at physiological concentrations influences carbohydrate metabolism and if so whether its effects differ in diabetic and nondiabetic humans. PMID- 2189769 TI - Morpho-cytochemical and biochemical evidence for insulin absorption by the rat ileal epithelium. AB - In order to investigate the mechanism through which insulin is absorbed by the intestinal epithelium and transferred to the circulation where it exercises its biological activity of lowering blood glucose levels, a combined biochemical morpho-cytochemical study was undertaken on rat ileal tissue, in vivo. Insulin was introduced into the lumen of the ileum in combination with sodium cholate and aprotinin and allowed to be absorbed for various periods of time. Analysis of blood samples from the inferior vena cava, at different time points has demonstrated an increase in plasma insulin followed by a decrease in blood glucose levels. The ileal tissues were studied at different time points after the introduction of the insulin, by applying the protein A-gold immunocytochemical technique. Insulin antigenic sites were detected with high resolution, at various levels of the enterocytes but were absent from goblet cells. At 2 to 5 min, the labelling was mainly associated with the microvilli and endocytotic vesicles in the apical portion of the epithelial cells. Some gold particles were in contact with the lateral membranes. At 10 min, the labelling was found at the level of the trans-side of the Golgi apparatus and mainly along the baso-lateral membranes of the epithelial cells. Labelling was also detected in the interstitial space. The control experiments have demonstrated the specificity of the labelling and confirmed the nature of the insulin molecules detected. Furthermore, the morphological study has confirmed that exposure of the tissue to the insulin cholate-aprotinin solution does not affect the integrity of the epithelium while promoting insulin absorption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189771 TI - Expression of reg protein in rat regenerating islets and its co-localization with insulin in the beta cell secretory granules. AB - Regenerating islets can be induced by the administration of poly(ADP-ribose) synthetase inhibitors to 90% depancreatized rats. In screening a regenerating islet-derived cDNA library, we previously isolated a novel gene. reg (regenerating gene), which encodes a 165-amino acid protein with a 21-amino acid signal sequence. In the present study, we have examined the expression and localization of reg protein in the regenerating islets by immunocytochemical techniques using a monoclonal antibody against a recombinant rat reg protein of 144 amino acids without the signal sequence. Light microscopy examination showed strong immunoreactivity for reg protein in the regenerating islets of the rats at two weeks and two months after 90% pancreatectomy, whereas reg protein was almost undetectable in normal rat islets or in the islets of the rats one year after the pancreatectomy. Almost all the reg protein-positive cells were stained for insulin. By applying the immunogold technique at the ultrastructural level, it was demonstrated that both reg protein and insulin occur in the central granular core of the regenerating Beta cell secretory granules. These results suggest that reg protein is synthesized in and secreted from the regenerating Beta cells and that its expression is closely associated with Beta-cell regeneration. PMID- 2189770 TI - Insulin regulation of glucose and lipid metabolism in massive obesity. AB - Eight obese patients and 12 normal individuals underwent a euglycaemic insulin clamp (20 and 40 mU m2-1.min-1) along with continuous infusion of 3-3H-glucose and 1-14C-palmitate and indirect calorimetry. Basal plasma glucose concentration (4.7 +/- 0.3 vs 4.4 +/- 0.2 mmol/l) was similar in the two groups, whereas hepatic glucose production was slightly higher in obese individuals (1.11 +/- 0.06 vs 0.84 +/- 0.05 mmol/min) in spite of higher plasma insulin levels (17 +/- 2 vs 6 +/- 1 mU/l; p less than 0.01). Insulin inhibition of hepatic glucose production was impaired in obese subjects. Glucose disposal by lean body mass was markedly reduced both at baseline (11.7 +/- 1.1 vs 15.6 +/- 0.6 mumol.kg-1.min-1; p less than 0.05) and during clamp (15.0 +/- 1.1 vs 34.4 +/- 2.8 and 26.7 +/- 3.9 vs 62.2 +/- 2.8 mumol.kg-1.min-1; p less than 0.01) Oxidative (12.2 +/- 1.1 vs 17.8 +/- 1 and 16.1 +/- 1.1 vs 51.1 +/- 1.7 mumol.kg-1.min-1; p less than 0.05 0.002) and non-oxidative glucose metabolism (3.9 +/- 1.1 vs 15.0 +/- 2.8 and 12.8 +/- 3.3 vs 38.2 +/- 2.2 mumol.kg-1.min-1; p less than 0.01-0.001) were impaired. Basal plasma concentrations of non-esterified fatty acids (635 +/- 75 vs 510 +/- 71 mumol/l) and blood glycerol (129 +/- 17 vs 56 +/- 5 mumol/l; p less than 0.01) were increased in obese patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189772 TI - Recruitment in a primary care trial on smoking cessation. AB - The purpose of this study was to describe and compare the rates of recruitment during a randomized clinical trial on smoking cessation in two primary care practices. One site was a five-physician private family practice setting with about 15,000 patients. During 34 days, 576 patients were screened, of whom 22% were smokers. Among the smokers screened, 54% consented, 33% refused consent, and 13% were called in too early to consent. The other site was a six-physician academic medical practice with about 16,000 patients. During 53 days, 1,692 subjects were screened, of whom 16.2% were smokers. Among the smokers, 19% consented, 81% refused consent, and none were called in early. The enrollment of smokers was 3.3 times greater in the private practice than the academic practice. At the first site, study personnel screened 26.6 subjects per day, whereas the practice receptionist screened only 13.4 subjects per day (P less than .01). A randomized trial of having subjects read the informed consent versus having study personnel read it to them showed no differences in recruitment. The data suggest that private practices may have greater potential for subject recruitment than academic sites, that using study personnel improves recruitment, and that having study personnel actively involved in informed consent does not improve recruitment. PMID- 2189773 TI - [Beta 2 microglobulin amyloidosis: a new complication of periodical hemodialysis treatment]. PMID- 2189774 TI - [Antacids and peptic ulcer]. PMID- 2189775 TI - Role of oxygen free radicals in carcinogenesis and brain ischemia. AB - Even though oxygen is necessary for aerobic life, it can also participate in potentially toxic reactions involving oxygen free radicals and transition metals such as Fe that damage membranes, proteins, and nucleic acids. Oxygen free radical reactions and oxidative damage are in most cases held in check by antioxidant defense mechanisms, but where an excessive amount of oxygen free radicals are produced or defense mechanisms are impaired, oxidative damage may occur and this appears to be important in contributing to several pathological conditions including aging, carcinogenesis, and stroke. Several newer methods, such as in vivo spin-trapping, have become available to monitor oxygen free radical flux and quantitate oxidative damage. Using a combination of these newer methods collectively focused on one model, recent results show that oxidative damage plays a key role in brain injury that occurs in stroke. Subtle changes, such as oxidative damage-induced loss of glutamine synthetase activity, may be a key event in stroke-induced brain injury. Oxygen free radicals may play a key role in carcinogenesis by mediating formation of base adducts, such as 8 hydroxyguanine, which can now be quantitated to very low levels. Evidence is presented that a new class of free radical blocking agents, nitrone spin-traps, may help not only to clarify if free radical events are involved, but may help prevent the development of injury in certain pathological conditions. PMID- 2189776 TI - Diet and metabolic development. AB - For many years, investigators have been concerned with mechanisms that control and alter genetically regulated development. An intriguing aspect of these mechanisms is the ability of environmental factors to induce certain metabolic processes. Animal studies have shown that dietary manipulation of cholesterol and fatty acid metabolism during development can have persistent and permanent effects. In addition, there appears to be a critical period when changes in the diet can have lasting consequences. The changes in the control exerted by nutritional factors on metabolic development coincide with three phases of development: prenatal, suckling, and weaning. The effects of diet on cholesterol and fatty acid metabolism throughout these three phases of development will be addressed in this review. PMID- 2189777 TI - Metabolic effects of dietary fructose. AB - Fructose, a naturally occurring hexose, is a component of many fruits, vegetables, and sweeteners. Because of the introduction of high fructose corn sweeteners in 1967, the amount of free fructose in the diet of Americans has increased substantially in the last 20 years. Fructose is sweeter, more soluble, and less glucogenic than glucose or sucrose, so it has been recommended as a replacement for these sugars in the diets of diabetic and obese people. Although an acute dose of fructose causes smaller increases in glucose and insulin than a comparable dose of glucose, there are a number of changes after dietary adaptation that may reduce its desirability as a sugar replacement in certain segments of the population. Fructose is absorbed primarily in the jejunum and metabolized in the liver. When consumed in excess of dietary glucose, it may be malabsorbed. Fructose is more lipogenic than glucose or starches, and usually causes greater elevations in triglycerides and sometimes in cholesterol than other carbohydrates. Dietary fructose has resulted in increases in blood pressure, uric acid, and lactic acid. People who are hypertensive, hyperinsulinemic, hypertriglyceridemic, non-insulin-dependent diabetic, or postmenopausal are more susceptible to these adverse effects of dietary fructose than healthy young subjects. Although consumption of fructose as a component of fruits and vegetables is an unavoidable consequence of eating a healthy diet, added fructose seems to provide little advantage over other caloric sweetners and compares unfavorably to complex carbohydrates in susceptible segments of the population. PMID- 2189778 TI - Transpyloric prolapse of a pedunculated polypoid gastric carcinoma. AB - A patient with transpyloric prolapse of a pedunculated polypoid gastric carcinoma is reported. Only three previous cases have been reported in the international literatures. However, in Japan, 33 cases of prolapsed gastric carcinoma have been reported during the past 30 years. Prolapsed gastric carcinoma should be included in the differential diagnosis of localized intraluminal filling defects in the duodenal bulb. Endoscopy and biopsy are essential for correct diagnosis. PMID- 2189779 TI - The renin-angiotensin system and the regulation of plasma cortisol in the flounder, Platichthys flesus. AB - The changes in arterial blood pressure and plasma cortisol concentration in response to exogenous angiotensin II (AII) and to manipulation of the endogenous renin-angiotensin system (RAS) have been examined in the flounder, Platichthys flesus. Intravenous [Asp1Val5]AII was pressor in a dose-dependent manner over the range of 0.25-250 micrograms/kg. Sequential blood sampling revealed steroidogenic stimulation, measured as change in plasma cortisol concentration, by doses of AII greater than 2.5 micrograms/kg. Enhanced circulating cortisol levels were measured some time after recovery of normal systemic blood pressure, suggesting that the change in plasma steroid concentration was not entirely dependent on the change in systemic blood pressure. Administration of the vasodilator papaverine produced immediate hypotension followed by gradual recovery in blood pressure, which was accompanied by a sustained increment in circulating cortisol. Both blood pressure recovery and the increased plasma steroid concentration were inhibited by prior treatment with the angiotensin converting enzyme inhibitor captopril. These results are consistent with a physiologically important role for the RAS in the control of plasma cortisol levels which complements its demonstrated pressor and dipsogenic actions in the flounder: the RAS may thus afford an integrating influence on the mechanisms of body fluid homeostasis in this euryhaline species. PMID- 2189780 TI - Immunoreactive luteinizing hormone-releasing hormone in the frog (Rana esculenta) brain: distribution pattern in the adult, seasonal changes, castration effects, and developmental aspects. AB - The present work describes the neuroanatomical distribution of the immunoreactive luteinizing hormone-releasing hormone (ir-LHRH) system in the brain of adult male and female, castrated male and developing Rana esculenta. No obvious sex differences in the distribution pattern of ir-LHRH were observed. Immunoreactive neuronal cell bodies are not contained within a single anatomically defined area of the brain. They are present as distinct groups in the olfactory bulbs, medial septal area, anterior preoptic area (APOA), retrochiasmatic area of the infundibulum, and interpeduncular nucleus-tegmentum area. Of the entire brain, the medial septal-APOA region exhibits the highest frequency of ir-LHRH cell bodies in both sexes. ir-LHRH fiber projections are present in the olfactory bulbs, medial septal area, APOA, floor of the diencephalon, subhabenular periventricular area in the epithalamus, lateral suprachiasmatic area, ventrolateral infundibulum, median eminence, pars nervosa, optic tectum, interpeduncular nucleus-tegmentum area, and rhombencephalon grey. Castration seems to bear no effect on the pattern of ir-LHRH system in the frog brain. The influence of castration consisted in decreased intensity of the immunostaining and frequency of occurrence of the septal-APOA neuronal cell bodies. In median eminence, castration also induced a sensible decrease in the immunoreactivity, whereas in the pars nervosa of 50-day castrates ir-LHRH fibers totally disappeared. During ontogenesis, ir-LHRH elements first become evident in stage 31 tadpoles (beginning of metamorphic climax); LHRH immunoreaction is restricted to the cell bodies and fibers in the APOA and some fibers in the ventral hypothalamus and a few in median eminence. This condition remains unaltered until stage 33 when the tail is almost totally resorbed. The possible implications of the ir-LHRH-containing brain areas in the different aspects of reproduction in the frog are briefly discussed. PMID- 2189781 TI - Phylogeny and ontogeny of gonadotropin-releasing hormone: comparison of guinea pig, rat, and a protochordate. AB - Immunoreactive gonadotropin-releasing hormone (ir-GnRH) was detected in brain extracts of newborn and 10-day-old rats and in adult guinea pigs; it was also present in extracts of the neural ganglion and gland of a protochordate. Radioimmunoassay (RIA) using different GnRH antisera after high-performance liquid chromatography (HPLC) revealed that the dominant form of GnRH is the mammalian form (pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) both during ontogenesis in the rat and in the adult guinea pig known to have variant forms of other peptide hormones. None of the other forms of GnRH identified in nonmammalian species to date appear to be present in the rat or guinea pig. A small amount of an unidentified HPLC early eluting form of GnRH is present, but detection by antiserum B-6 implies that it is also mammalian GnRH, with the possibility of changes in positions 2-4. The molecular form of GnRH in a protochordate, the sea squirt Chelyosoma productum, is distinct from salmon and mammalian GnRHs. Cross-reactivity with the sea squirt GnRH-like molecule was highest with an antiserum made against lamprey GnRH; the same antiserum was used to stain nerve fibers in the neural ganglion and some of its roots. This is the first report using RIA, HPLC, and immunocytochemistry to show that protochordates have GnRH-like material. The results suggest that GnRH may have been present at the transition between the invertebrates and vertebrates. PMID- 2189783 TI - The FUR1 gene of Saccharomyces cerevisiae: cloning, structure and expression of wild-type and mutant alleles. AB - The FUR1 gene of Saccharomyces cerevisiae encodes uracil phosphoribosyltransferase (UPRTase) which catalyses the conversion of uracil into uridine 5'-monophosphate (UMP) in the pyrimidine salvage pathway. The FUR1 gene is included in a 2.1 kb genomic segment of DNA and is transcribed into a 1 kb poly(A)+mRNA. Sequencing has determined a 753 bp open reading frame capable of encoding a protein of 251 amino acids. The FUR1 genes for three recessive fur1 alleles, having different sensibilities to 5-fluorouridine (5-FUR) but identical levels of resistance to 5-fluorouracil (5-FU), were cloned and sequenced. Single bp changes located in different regions of the gene were found in each mutant. Two in vitro-constructed deletions of the FUR1 gene have been integrated at the chromosomal locus, giving strains with 5-FURR and 5-FURR mutant phenotype. Assays of UPRTase, uridine kinase, uridine ribohydrolase and uridine 5'-monophosphate nucleotidase enzymatic activities, in extracts of strains where the FUR1 gene is overexpressed or deleted, indicate that the FUR1 encoded protein possesses only UPRTase activity. PMID- 2189782 TI - Balbiani ring 3 in Chironomus tentans encodes a 185-kDa secretory protein which is synthesized throughout the fourth larval instar. AB - We have continued to map and identify genes encoding a family of secretory proteins. These proteins are synthesized in larval salivary glands of the midge, Chironomus tentans, and assemble in vivo into insoluble silk-like threads. The genes for several secretory proteins exist in Balbiani rings (BRs) on salivary gland polytene chromosomes. A randomly primed cDNA clone, designated pCt185, hybridized in situ to BR3 and was shown on Northern blots to originate from a salivary gland-specific 6-kb poly(A) + RNA. The partial cDNA sequence contained 483 nucleotides including one open reading frame (ORF) encoding 160 amino acids (aa). A striking feature of the ORF was the periodic distribution of cysteine residues (Cys-X-Cys-X-Cys-X6-Cys) which occurred approximately every 22 aa. A cDNA-encoded 18-aa sequence was selected for chemical peptide synthesis. When affinity-purified antipeptide antibodies were incubated with a Western blot containing salivary-gland proteins they reacted specifically with a 185-kDa secretory protein (sp185). Developmental studies showed that sp185 and its mRNA were present in salivary glands throughout the fourth larval instar. Thus sp185 and a family of 1000-kDa secretory proteins are encoded by a class of genes that are expressed throughout the fourth instar. This contrasts with the developmentally regulated expression of the sp140 and sp195 genes whose expression is maximal during the prepupal stages of larval development. PMID- 2189784 TI - A microtransfection method using the luciferase-encoding reporter gene for the assay of human immunodeficiency virus LTR promoter activity. AB - A microtransfection method, using either the DEAE-dextran or the Ca.phosphate procedure has been developed. A plasmid expressing the luciferase-encoding gene under the control of the human immunodeficiency virus (HIV) LTR promoter was constructed. Transfections were performed in 96-well plates, allowing statistical evaluation of the results. This microtransfection method requires the use of 100- to 1000-fold less plasmid and cells than in a conventional chloramphenicol acetyl transferase (CAT) assay. A Luciferase index which takes into account cell viability after transfection has been defined using a semi-automated absorbance assay. A 20-h incubation period post-transfection is sufficient for optimal results. Basal long terminal repeat activity and autologous Tat transactivation were studied in various lymphoid, monocytic and adherent human cell lines. Infection of microtransfected cells by HIV activated luc expression. This assay can thus also be used for rapid detection and quantitation of HIV. Antiviral activities of drugs can be assessed in a two-day test. PMID- 2189785 TI - An improved method for yeast 2 microns plasmid curing. AB - SMR1-410, a dominant resistance marker, was cloned into the FLP gene of 2 microns DNA to produce the chimeric YEp vector pWX823B. Selection for SMR1-410 at high concentrations of sulfometuron methyl maintained pWX823 at high copy number and resulted in the rapid and efficient loss of native 2 microns DNA. Using this protocol approximately 15% of the cells monitored showed loss of 2 microns DNA. The curing methodology is more efficient and convenient than previous methods and has the added advantage of being applicable to wild-type prototrophic cells. PMID- 2189786 TI - Structure and transcriptional control of the Saccharomyces cerevisiae POX1 gene encoding acyl-coenzyme A oxidase. AB - We have cloned the Saccharomyces cerevisiae gene coding for the peroxisomal enzyme: fatty acyl-CoA oxidase (POX). The gene (named POX1) is unique in S. cerevisiae and has been identified through homology with the POX4 and POX5 genes of Candida tropicalis. The POX1 gene encodes a 84-kDa POX protein composed of 748 amino acids. The identity between the S. cerevisiae and C. tropicalis enzymes is about 40%, and there is a greater degree of similarity between the N termini than the C termini. A disruption of the POX1 coding sequence diminishes the ability of yeast cells to grow on oleic acid as a sole carbon source. The expression of the POX1 gene is regulated at the level of transcription, and is induced more than 25 fold by the addition of oleic acid to the medium. PMID- 2189787 TI - Synthesis of papain in Escherichia coli. AB - We have transferred the cloned papain genetic information into an expression vector (pT7-7) regulated by the T7-promoter and have obtained in vitro expression as well as expression in Escherichia coli. In Western blots the proteins produced are immunologically recognizable as papain. Multiple forms of specific but differing sizes are detected, suggesting either that initiation can occur at more than one of the upstream methionines, or that the enzyme is processed after synthesis. PMID- 2189788 TI - Adenovirus proteinases: comparison of amino acid sequences and expression of the cloned cDNA in Escherichia coli. AB - Adenoviruses (Ad) synthesize serine-center endoproteinases (AdEPs) responsible for maturation cleavages within the virus particle. Many questions regarding these enzymes remain unanswered because previous studies utilized crude cells or viral lysates as the enzyme source. Here, we report on the comparison of the amino acid (aa) sequences of several AdEPs and on the expression of the cDNA of the Ad2Ep in Escherichia coli. The AdEPs consist of about 200 aa and their size is around 23 kDa. Among the seven sequences known, 60% of aa were strictly conserved. The usual serine proteinase active site sequence, GDSGG, is absent. The recombinant Ad2EP, produced by an inducible vector as a protein-A fusion product is capable of autocatalytic cleavage, and of cleaving its natural viral substrates as well as foreign proteins. Therefore, other viral proteins or mammalian specific post-translational modifications are not required for enzyme activity. PMID- 2189789 TI - Construction of a neo fusion gene for expression in both prokaryotic and eukaryotic cells. AB - A high-copy-number plasmid, pLink, was constructed to allow the direct selection in Escherichia coli of a neo fusion gene capable of conferring Geneticin (G418) resistance on mouse L cells. pLink was derived from pdMmtneo by insertion of a KpnI linker within the 5'-coding region of the neo gene. This created a minus-one frameshift mutation resulting in a translational termination within the N terminal region of the protein. The Neo activity was restored by insertion into the modified neo gene of a piece of coding sequence derived from human HPRT cDNA. The resulting plasmid, pAH, was microinjected into mouse A9 cells and shown to confer resistance to G418. PMID- 2189790 TI - Secretion of N-glycosylated human recombinant interleukin-1 alpha in Saccharomyces cerevisiae. AB - We have expressed fragments of the cDNA coding for mature human interleukin-1 alpha (hIL-1 alpha) in Saccharomyces cerevisiae. Mature hIL-1 alpha contains one potential N-linked glycosylation site that is not recognized in mammalian cells. Translational fusions to either one of three yeast signal sequences resulted in secretion of bioactive, N-glycosylated hIL-1 alpha. The extent of glycosylation was significantly reduced using the alpha-factor signal sequence, which itself contains three N-linked glycosylation sites known to be core glycosylated. N glycosylation has no effect on biological specific activity. PMID- 2189791 TI - Homesharing: how social exchange helps elders live at home. AB - Social exchange theory is used to analyze the relationships in traditional and caregiving homesharing arrangements. Satisfaction with basic money and service exchanges is high among the majority in both arrangements. In traditional matches, client satisfaction is also related to life style fit, amount of social interaction desired and received, and amount of lodger access in the provider's home. In caregiving matches, satisfaction is also related to the intensive interpersonal relationship developed between sharers; stress is a particular problem for the caregiver. PMID- 2189792 TI - Impacts associated with special care units in long-term care facilities. AB - This study is a comprehensive, longitudinal assessment of the characteristics of special care patients. Demented patients in special care units (SCUs) within four nursing homes were compared with their demented counterparts in the same facilities who were not placed in SCUs. Results of this preliminary study suggest that the two groups differ in level of cognitive impairment, in behavior, and in functional and physical status. No deleterious or beneficial effects were associated with SCU residence during a 6-month period. PMID- 2189793 TI - Milestoning: evoking memories for resocialization through group reminiscence. AB - An empirically conceived group reminiscence program was developed at a psychiatric center to evoke use of communication skills by geriatric residents. The goals were to tap into memories of a period before the patients' onset of dysfunctional mental illness and to prompt positive feelings during the guided discussions, thereby allowing for more frequent, appropriate interaction. Multisensory vivid imagery was employed to stimulate remembrances and increased communication. PMID- 2189794 TI - Induction of haem oxygenase as a defence against oxidative stress. AB - Cells respond to metabolic perturbations by producing specific stress proteins. Exposure of mammalian cells to various forms of oxidative stress induces haem oxygenase, the rate-limiting enzyme in haem degradation. This response is proposed to represent an antioxidant defence operating at two different stages simultaneously. It (i) decreases the levels of the potential pro-oxidants haem and haem proteins such as cytochrome P-450 and protoporphyrinogen oxidase, and (ii) increases the tissue concentrations of antioxidatively active bile pigments. PMID- 2189795 TI - [Hydrops fetalis in tachycardia: diagnostic and therapeutic procedures]. AB - We report on a 33-year-old para II who was admitted to our hospital in her 29th gestational week with extensive fetal hydrops. Examinations showed a fetal supraventricular tachycardia with biventrical cardiac insufficiency. Digoxin was given both to the mother and to the fetus. At first, this treatment seemed to have no effect. Over a period of several weeks, however, oral therapy with digoxin and verapamil resulted in a stabilized fetal heart rate (175-180 beats/min). Signs of fetal cardiac insufficiency disappeared almost completely. In the 39th week the child was born spontaneously. Clinical examination revealed only a slight cardiac insufficiency. New possibilities of intrauterine therapy are discussed in the light of this case and other reports in the literature. PMID- 2189797 TI - [Sore throat: an analysis of medical management in a community clinic]. AB - The diagnostic approach to sore throat and its treatment by 7 doctors was studied in 692 community clinic patients. Redness of the throat, the commonest clinical feature in all age groups, was present in 88%. The prevalence of other clinical findings varied in the different age groups. 54% of the patients, most of whom were less than 13 years old, were treated initially with antibiotics. Most of the physicians prescribed penicillin V (average, 8.4 days). From 11 (13%) of the throat cultures taken from children under the age of 4, beta hemolytic streptococci (BHS) were grown. Based on throat cultures, antibiotics had been given unnecessarily in 53% of those in whom it was initially prescribed, and wrongly withheld in 10% of those who initially did not receive them. This study reveals an urgent need for a rapid and accurate method of detecting BHS in patients with sore throat. PMID- 2189796 TI - Coagulation disturbances in cancer of the breast and colon measured with specific monoclonal antibody enzyme immunoassay for fibrin-fibrinogen degradation products. AB - Disturbances of coagulation were measured in breast cancer, colon cancer and benign breast disease using an enzyme immunoassay against total plasma fibrinogen and fibrin degradation products (TDP). Results were compared with measurements of fibrinopeptide A (FPA) and of serum fibrinogen-related antigen (FRA). Plasma TDP before surgery was significantly higher in colon cancer than in breast cancer patients (p = 0.0009) or in benign breast disease (p = 0.0292). A post-operative rise in TDP at 4 months (colon cancer) or 9 months (breast cancer) was associated with early recurrent disease (p less than 0.0173 for colon cancer, p less than 0.1835 for breast cancer). No such association was noted with FPA or FRA measurements. TDP may prove to be of value in detecting activation of coagulation by malignant disease. PMID- 2189799 TI - [Urolithiasis: I. Prevention and related pharmacotherapy]. PMID- 2189798 TI - [Proliferating cell nuclear antigen-A]. PMID- 2189801 TI - [Late paraphrenia]. PMID- 2189800 TI - [Pulmonary artery catheter: essential technology or iatrogenic epidemic?]. PMID- 2189802 TI - [Postpartum thyroid dysfunction]. PMID- 2189803 TI - [Aloe vera--the real truth]. PMID- 2189804 TI - [Cryptosporidiosis]. PMID- 2189805 TI - [Sleep and scoliosis]. PMID- 2189806 TI - [School survey for idiopathic scoliosis]. PMID- 2189807 TI - [A simple qualitative method for assessing microalbuminuria in diabetics]. AB - Diabetes mellitus is one of the most important causes of kidney diseases, the first sign of which is albuminuria. It is now possible to detect microalbuminuria before the appearance of larger quantities. We compared a simple qualitative test for microalbuminuria (change in color of a tablet containing bromphenol blue on addition of urine) with a more elaborate quantitative immunoturbidometric method. Of 109 samples tested 31 were positive by the quantitative method and 29 of these were positive by the tablet method. Out of the 78 negative by the quantitative method only 4 were positive by the qualitative test. The sensitivity of the tablet test was 93.5%, specificity 94.0%, positive predictive value 87.9%, negative predictive value 97.4%, false positive rate 5.2%, and false negative rate 6.2%. We conclude that the tablet test is simple and accurate and is suitable both for screening of large populations and for the diagnosis of individual cases of microalbuminuria. PMID- 2189808 TI - [Use of scoring systems in the critical surgical patient]. PMID- 2189809 TI - [Role of plasmapheresis in the treatment of systemic lupus erythematosus]. PMID- 2189810 TI - [Surgical management of pulmonary metastases--current status]. PMID- 2189811 TI - [Relations between myopia, education and intelligence]. PMID- 2189812 TI - [Community surveys as an epidemiologic research method in psychiatry]. PMID- 2189813 TI - [Severe head injury--pathophysiology and initial treatment]. PMID- 2189814 TI - [Delayed muscle soreness]. PMID- 2189815 TI - [Bronchopulmonary dysplasia: 1. Pathogenesis and complications]. PMID- 2189816 TI - [Excitatory amino acid and their involvement in pathological processes in the brain]. PMID- 2189817 TI - [Coronary artery surgery--overview]. PMID- 2189818 TI - [Coronary artery bypass in the elderly]. PMID- 2189819 TI - Characterization of obese women with reduced sex hormone-binding globulin concentrations. AB - Factors influencing sex-hormone binding globulin (SHBG) concentrations in obesity are poorly understood. Preliminary observations suggest that dietary lipids may be involved and there are data confirming a direct inhibiting effect of insulin. Since only some obese subjects show lowered SHBG levels, we performed this study with the aim of defining obese women with low SHBG (LSO) (2 SD above normal values) in comparison with those presenting normal globulin concentrations (NSO). These groups were selected from a larger group of obese women with a history of normal menses and aged less than 40 years. An age-matched group of normal weight healthy women served as controls. Both LSO and NSO had similar body mass index and percentage body fat, but the waist to hip girth ratio (WHR), an index of body fat distribution, was significantly higher in LSO (0.88 +/- 0.04) than in NSO (0.81 +/- 0.09; P less than 0.05). Gonadotropin and androgen concentrations were similar in both groups, whereas estrone (E1) levels were higher in LSO (32.8 +/- 15.8 pg/ml) than in NSO (19.4 +/- 6.2 pg/ml; P less than 0.05; controls: 23.5 +/- 7.8 pg/ml; P less than 0.05). Moreover, compared to NSO, LSO women had significantly higher glucose-stimulated insulin and C-peptide levels. Partial regression analysis revealed significant correlation coefficients between SHBG, stimulated insulin values (r = -0.38; P less than 0.05) and WHR (r = 0.40; P less than 0.005). Therefore, compared to NSO, LSO women have distinctive clinical and endocrine characteristics, namely more pronounced hyperinsulinemia, higher E1 concentrations and a central type body fat distribution. PMID- 2189820 TI - Intranasal insulin administration in insulin dependent diabetes: reproducibility of its absorption and effects. PMID- 2189821 TI - Micronodular transformation (nodular regenerative hyperplasia) of the liver: a report of 64 cases among 2,500 autopsies and a new classification of benign hepatocellular nodules. AB - Nodular regenerative hyperplasia is defined by hepatocellular nodules distributed throughout the liver in the absence of fibrous septa between the nodules. Most reports have been single cases so that the prevalence and clinical significance of nodular regenerative hyperplasia is uncertain. In this study, the hepatic histology of 2,500 consecutive autopsies was reviewed. A spectrum of nodular transformation was found with nodular regenerative hyperplasia present in 2.6% of autopsy livers and qualitatively similar but lesser degrees of nodular transformation in a further 10.2%. Nodular transformation was also seen in 47% of livers with cirrhosis and 69% with incomplete cirrhosis. Obliteration of many small portal veins was seen in all cases with nodular regenerative hyperplasia, but only 4.7% of these had evidence of portal hypertension. The prevalence of various clinical states was compared in nodular regenerative hyperplasia and in controls. The results confirm, extend and quantify the spectrum of associated diseases. Nodular regenerative hyperplasia occurs in 5.6% of individuals over age 80 and with increased frequency in patients with systemic arteritis, polymyalgia rheumatica, massive tumor infiltration and mineral oil deposition. Nodular regenerative hyperplasia appears to be the hepatic analogue of arterial and arteriolar nephrosclerosis. A new classification of nodular transformation is proposed that encompasses the spectrum of lesions described here and the previously defined entities of focal nodular hyperplasia, partial nodular transformation and "cirrhosis telangiectasia hepatis." The major conclusion is that nodular regenerative hyperplasia is a secondary and nonspecific tissue adaptation to heterogeneous distribution of blood flow and does not represent a specific entity. PMID- 2189822 TI - Alzheimer's disease: clinical update. PMID- 2189823 TI - Electroconvulsive therapy: an update. AB - Electroconvulsive therapy (ECT) is a safe, rapidly acting, and very effective form of treatment for severe affective illness. In recent years the limitations of available psychopharmacotherapies and the pressures of cost containment appear to be encouraging the increasing use of ECT. The authors provide an overview of electroconvulsive therapy as a treatment modality, focusing on indications, contraindications, adverse effects, and contemporary ECT technique, including recent modifications in electrode placement, stimulus wave form, and dosage intensity. They urge that adequate training be provided for medical and nursing personnel who administer ECT and that facilities monitor practitioners' competence by specific privileging. PMID- 2189824 TI - Utilization review: theory, practice, and issues. AB - Utilization review is now carried out by most hospitals and many health care agencies, government-sponsored local agencies, third-party payers, and private companies, yet few practical explanations of the process are available. In this guide, the author differentiates between internal and external review and their likely outcomes, outlines the development of a utilization review system, and describes the stages and levels of review. Psychiatric utilization review is especially difficult to carry out; thus it rarely goes beyond evaluating need for hospitalization and length of stay. Utilization review in general still must deal with issues related to confidentiality, the clinical responsibility of the reviewer, and whether certification for admission can reward poor or inappropriate care. PMID- 2189825 TI - Detection of low numbers of lymphocyte surface membrane molecules using concentration immunofluorescence analysis (CIA). AB - Using viable lymphocytes in a concentration immunofluorescence assay (CIA), conditions were ascertained which allow detection of low numbers of surface membrane molecules. Utilizing 3 layer labeling [monoclonal antibody (MAb) specific for the membrane molecule, biotin-conjugated antibody specific for the MAb, and R-phycoerythrin-strepavidin], large numbers of lymphocytes in the assay wells, and the Pandex Fluorescence Concentration Analyzer, a fluorescence signal significantly above background was generated by as few as 8 x 10(7) molecules among 4 x 10(5) lymphocytes. Experiments using membrane molecules (Fc gamma R II, Ia antigens, Ly-39) which differ considerably in their level of expression indicated that comparable signals were generated by equivalent numbers of labeled molecules in a cell population irrespective of the number of molecules on an individual cell. Thus, CIA is theoretically capable of detecting membrane molecules whose expression is as low as 2 x 10(2) per cell. CIA should be useful in the assay of cytokine receptors and other lymphocyte membrane molecules expressed at low levels, and in the development of MAb specific for these molecules. PMID- 2189826 TI - Generation and characterization of a murine monoclonal antibody to cervical glandular epithelium using mice rendered tolerant to cervical squamous epithelium. AB - Murine monoclonal antibodies that distinguish glandular from squamous epithelia in human tissue were generated using a procedure that involved tolerization prior to immunization. Tolerization was achieved by injection of newborn (24 hrs old) Balb/c mice with extract of normal cervical tissue containing squamous epithelium (the tolerogen). Three weeks later, mice showing no evidence of antibodies to tolerogen in their sera were immunized with an extract of cervical tissue containing both glandular and squamous epithelia. Following immunization, the sera from mice subjected to this treatment showed strong reactivity with glandular cells but not with squamous cells in sections of frozen tissue examined by an indirect immunohistological method. Spleen cells from mice showing this pattern of serum reactivity were used as fusion partners with a mouse myeloma cell line in order to generate monoclonal antibodies. Following extensive screening, one monoclonal antibody (designated anti-GEA.49) was selected for further study on the basis of reactivity with high affinity to glandular epithelium and a complete absence of staining of squamous and connective-tissue cells. Detailed tests of specificity and patterns of reactivity indicate that the antigen detected by the antibody is expressed on the apical plasma membrane of glandular epithelia and is a glycoprotein with an apparent molecular weight of 49 kilodaltons. Both immunohistological and biochemical methods demonstrated the expression of the antigen on glandular epithelia but not on squamous epithelia from several sources, underlining the usefulness of tolerization/immunization approach for generating antibodies with particular specificity requirements. PMID- 2189827 TI - Analysis of T lymphocyte reactivity to complex antigen mixtures by the use of proteins coupled to latex beads. AB - This report describes a suitable model for analysing heterogeneous T cell responses to complex foreign antigens using coated polystyrene beads. The advantage of this technique is that it allows the simple removal of detergents from bound antigen so that biochemically separated antigens or crude antigen mixtures can be used. Furthermore, due to the enhanced uptake of latex-bound antigens by phagocytic antigen-presenting cells (APC), very small amounts of antigen will suffice for activation of T cells in vitro. The potential use of this technique to analyse relevant T cell responses to antigens which are difficult to obtain purified in bulk quantities, is discussed. PMID- 2189828 TI - Red cell phosphoglycerate kinase in insulin-dependent diabetes mellitus. AB - Red cell phosphoglycerate kinase (PGK) activity was determined in normal individuals and patients with, type I (insulin-dependent) diabetes and insulin treated diabetes. The PGK activity was significantly (P less than 0.001) elevated in diabetes, however it is restored to normalcy after insulin treatment (normal 282.54 +/- 9.46, type I diabetic 342.06 +/- 6.24, insulin treated diabetic 292.66 +/- 7.12 IU/g haemoglobin at 37 degrees C). No significant alteration was observed in the percentage of PGK bound to the membrane fraction of red cells in all the three conditions. The results indicate that the increased PGK activity is a result of a regulatory mechanism induced by the fluctuation of ATP level in response to elevated Na:K pump rate of erythrocytes in type I diabetes mellitus. PMID- 2189829 TI - Evaluation of hepatoprotective activity of picroliv (from Picrorhiza kurroa) in Mastomys natalensis infected with Plasmodium berghei. AB - Administration of picroliv, a standardized fraction of alcoholic extent of Picrorhiza kurroa (3-12 mg/kg/day for two weeks) simultaneously with P. berghei infection showed significant protection against hepatic damage in Mastomys natalensis. The increased levels of serum glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), alkaline phosphatase, lipoprotein-X (LP-X) and bilirubin in the infected animals were marked reduced by different doses of picroliv. In the liver, picroliv decreased the levels of lipid peroxides and hydroperoxides and facilitated the recovery of superoxide dismutase and glycogen. Picroliv had no effect on the degree of parasitaemia. PMID- 2189830 TI - Increased brainstem angiotensin-I levels in chronic 2 KIC hypertensive rats. AB - A study was undertaken on the role of brainstem renin-angiotensin system in maintenance of hypertension in chronic renovascular hypertensive rats. Hypertension was induced by unilateral renal artery clamping, while the contralateral kidney was left intact (2 KIC). Blood pressure (BP), plasma renin activity (PRA) and brainstem angiotensin (ang-I) levels were measured after 24 days, in hypertensive and sham-operated animals. In separate subgroups of these animals, the effect of intracerebroventricular administration of captopril on the parameters listed was studied. The results showed high ang-I levels in 2 KIC rats as compared to controls (P less than 0.05). Captopril administration (500 micrograms/50 microliters icv) caused a fall in BP and increase in brainstem ang I levels (P less than 0.01). In control animals, however, captopril produced a rise in BP without any significant change in brainstem ang-I levels. Peripheral plasma renin activity was normal, despite significant sodium retention in 2 KIC rats. The results are suggestive of activation of brainstem renin-angiotensin system (RAS) in chronic 2 KIC hypertension. PMID- 2189831 TI - Sensitivity of the different tests of enterotoxigenicity of Escherichia coli and their correlation. AB - Enterotoxigenicity of E. coli isolates was tested in 136 cases of acute gastroenteritis. Heat labile toxin (LT) produced in-vitro was tested in rabbit ileal loop (RIL); vero cell line and Biktn plate. The results of live cultures were evaluated in RIL. The overall data of these four models were not statistically different. Elaboration of LT in these four models ranged from 14 21.4%. Out of the 20 LT producing strains 14 (70%) also revealed ST. Of the 6 positive reactors on vero cell line, appeared to produce vero toxin (VT) only. Out of 29 LT positive E. coli, 1 (3.45%) and 2 (6.89%) strains respectively revealed colonising factor antigen (CFA) I and II. The high incidence of ETEC showing both LT and ST has been highlighted in the age group 0-4 years, and its impact on nutritional status is discussed. PMID- 2189832 TI - Small-airways dysfunction in never smoking asbestos exposed Danish plumbers. AB - Among 701 Copenhagen plumbers we examined the lung function of 23 never smokers, who had removed asbestos insulation and intermittently been exposed to high levels of asbestos for about 25 years without being exposed to welding fume. The plumbers had significantly lower TLC, MEF25, MEF50, closing volume and closing capacity in comparison to 23 never smoking electricians without asbestos exposure. There was no reduction in TLCO. Pulmonary clearance of aerosolized 99mTc-DTPA was normal indicating that the asbestos had not induced increases in pulmonary epithelial permeability. However, in 11 of the 23 plumbers the 99mTc DTPA ventilation scintigrams had a slightly irregular and spotty appearance, which together with the results of the lung function tests are suggestive of small airways' dysfunction. None of the subjects had symptoms or clinical signs of lung disease. PMID- 2189833 TI - Is calcitonin gene-related peptide (CGRP) a regulator of blood pressure in hemodialysis patients? PMID- 2189834 TI - Eicosanoids and blood pressure during hemodialysis. PMID- 2189835 TI - Newcastle bone disease in Hong Kong: a study of aluminum associated osteomalacia. AB - We measured serum aluminum concentrations in 104 haemodialysis patients from 3 centres in Hong Kong. We found that the 52 patients dialyzed in unit A had much higher mean aluminium levels (100 micrograms/L) than those from the other two units (61 and 39 micrograms/L respectively). In unit A, where water treatment by reverse osmosis had been introduced only recently, 30.8% of patients had fractures/looser zones, 46.2% had rugger-jersey spine and 28.8% had skeletal erosions. When these patients were divided into two groups according to whether their serum aluminium concentration was below or above 100 micrograms/l, the latter patients had significantly lower alkaline phosphatase, serum phosphate, and higher total prescribed dose of aluminium hydroxide. It was concluded that both dialysate aluminium and oral aluminium intake seemed to have contributed to the high incidence of osteomalacic fractures among Unit A patients. In eight of these patients serum aluminium increased by more than 150 micrograms/L after four weeks of receiving 1.5 g desferrioxamine twice weekly. Serial X-rays showed that the mean time after dialysis for the appearance of fractures/Looser zones was 72 months. Three patients developed fractures/Looser zones after successful renal transplantation; and it was postulated that the prompt excretion of aluminium permitted increased osteoclastic activity, resulting in fractures in these patients. PMID- 2189836 TI - Clinical and laboratory evaluation of hemocarboadsorption in autoimmune bullous dermatoses. AB - Hemocarboadsorption (HCA) with the following immunosuppressive therapy was used to treat 48 patients with pemphigus vulgaris (PV) and 31 patients with bullous pemphigoid (BP) in the acute phase. The levels of autoantibodies, eicosanoids, endoproteases and their inhibitors as well as interleukin (IL) 1 and IL 2 production and absorption of exogenous IL 2 were examined in the treatment dynamics. The therapeutic effect of HCA was displayed in prompt disease remission in 43 PV and 29 BP patients. Clinical improvement was accompanied by antibody elimination and interleukin cascade reaction normalization. HCA resulted in growth of patients' serum immunosuppressive activity. It was concluded that HCA has some immunoregulatory effect (Int J Artif Organs; 1990: 13: 181-88). PMID- 2189837 TI - The use of hypnosis in the treatment of bulimia nervosa. AB - Promising research data, relating hypnotizability and the possible presence of a dissociative mechanism in bulimic individuals, stimulated the present authors to incorporate hypnosis in their directive and multidimensional treatment of bulimic patients. Important strategies and how and when they can be applied in the different phases of treatment are described. In many cases, hypnotherapeutic techniques may enhance the effectiveness of cognitive behavioral and interactional strategies in the treatment of bulimic patients. In other instances, the incorporation of hypnosis may help both the therapist and patient to discover new pathways to facilitate the therapeutic process. PMID- 2189838 TI - Broaching and exploring the question of combined group and individual therapy. AB - Combined therapy is defined as concurrent dyadic and group therapy with the same therapist. This paper focuses on a neglected aspect of combined therapy: broaching and exploring this question with one's individual patient. The author shows how raising this question: (1) alters the therapeutic field whether or not the patient joins; (2) can sharpen the therapist's understanding of the indications and contraindications for group membership; (3) offers untapped therapeutic approaches and opportunities to classify issues in the individual treatment; and (4) stirs up countertransference issues related to issues of profitability, the transference of the patient in individual treatment, and the transference of the group-as-a-whole. Several case examples are provided. PMID- 2189839 TI - The value of self-administered peri-operative physiotherapy. AB - Sixty patients undergoing cholecystectomy were studied and allocated at random to a control group and a treated group to whom physiotherapy instruction was given. Respiratory function tests were recorded pre-operatively and on the 2nd and 5th post-operative days. These showed no statistical difference in values pre operatively, a statistically significant difference in value in both groups for all tests on the 2nd postoperative day, with maintenance of such reduced value for forced vital capacity (F.V.C) and peak flow (P.F.) in the control group on the 5th post-operative day. PMID- 2189840 TI - Granulomatous hepatitis in secondary syphilis. AB - An unusual case of a well-documented granulomatous hepatitis in secondary syphilis in a 47-year-old male is presented. This hepatic pathology in secondary syphilis is summarised, and a review of the literature regarding syphilitic granulomatous hepatitis presented. PMID- 2189841 TI - Localised Wegener's granulomatosis--a difficult and delayed diagnosis. Clinical report and literature review. AB - A case of localised Wegener's granulomatosis presenting with central nervous system symptoms and signs is described. The difficulties of early diagnosis are high-lighted and the diagnostic criteria of the disease are discussed. PMID- 2189842 TI - Psychological immunization: theory, research, and current health behavior applications. PMID- 2189843 TI - A randomized study of the efficacy of adjuvant local graft irradiation following renal transplantation. AB - A prospective randomized study investigating the effectiveness of adjuvant local graft irradiation (LGI) following renal transplantation was performed at Georgetown University Hospital from 1983 until 1988. One hundred and thirty-eight patients were enrolled in the study with 117 patients receiving cadaver kidney transplantations and 21 patients receiving living related kidney transplantations. Seventy-one patients were randomized to receive adjuvant local graft irradiation consisting of 600 cGy in four fractions with chemical immunosuppression whereas the remaining 67 patients received chemical immunosuppression only (control group). The two groups were comparable at entry with respect to potentially important prognostic variables. Median follow-up for all patients was 30 months. The 3-year actuarial allograft success rate was 75% and 68% for the local graft irradiation and control groups, respectively. A nonsignificant trend favoring the irradiated group was noted. Subgroup analysis of the 21 recipients of kidneys from living related donors suggested an improvement in allograft survival for the local graft irradiation arm. Cadaver allograft survival was not significantly different between the two treatment arms. There was no apparent benefit in kidney function or time to the first rejection episode in the group receiving local graft irradiation. PMID- 2189844 TI - A technique for delivery of total body irradiation for bone marrow transplantation in adults and adolescents. AB - With the increasing use of bone marrow transplantation for cancer, total body irradiation is becoming a more commonplace procedure in many of the larger centers across the country. The technical difficulties in delivering homogenous doses of radiation to the whole body are significant and involve many factors such as creation of a homogeneous, "flat" beam of radiation, and dealing with variations in patient thickness and tissue homogeneity, particularly in the lung. In addition, techniques must be used to safely and efficiently deal with patients who are usually very ill and require long treatment times. Although there is often an advantage in terms of dosimetry to using an AP/PA treatment technique, many institutions use parallel opposed lateral beams because of equipment and facility limitations. A technique has been devised that enables total body irradation to be given by an AP/PA technique using equipment available in many radiotherapy departments. Patients are supported in an upright position during treatment by means of a modified harness attached to the ceiling of the treatment room. Lung compensators are fixed to individually fitted "vests," allowing the patient moderate amounts of movement during treatment while maintaining the position of the compensator relative to the lungs. Thermoluminiscent dosimeter (TLD) dose measurements in a phantom indicate that this system can deliver accurate and homogeneous doses to lung tissue, while allowing a good degree of patient comfort and safety during the long treatment times that are required. PMID- 2189845 TI - Systemic radiotherapy--the new frontier. AB - The present day use of systemically administered isotopes and conjugated isotopic combinations are reviewed. Administration of 131Iodine in thyroid cancer led to a 97% local control and 50% complete remission of pulmonary metastases. Specificity directed isotopic therapy (metabolic, hormonal, and antibody) is discussed and includes factors such as tumor physiology and isotopic linkage. The clinical results and new knowledge being gained in Hodgkin's disease, non-Hodgkin's, colorectal, hepatoma, intrahepatic biliary and gliomatous cancers are reviewed. The dose response relationship to tumor remission is demonstrated in Hodgkin's treated with 131I antiferritin (40% partial remission) and more recently 90Yttrium antiferritin (50% complete response). Varied routes of administration, the problem of anti-antibody and bone marrow transplantation are discussed. Finally, the challenge to radiobiologists, physicists, chemists, immunologists, nuclear radiologists, and radiation oncologists is emphasized by definition of the new laboratory and clinical approaches being developed in systemic radiation therapy. PMID- 2189846 TI - Radiation-induced cancer as a factor in clinical decision making (the 1989 ASTRO Gold Medal address). AB - 1. Ionizing radiations are weak carcinogens. Under certain conditions they can induce cancers in experimental animals and humans. 2. This potential carcinogenicity has been a deterrent to the use of radiation therapy despite its many advantages in the management of patients with cancers. 3. In a range of clinical situations, such as the irradiation of cancers arising in the head and neck, breast, prostate and skin, an increase of second cancers can not be detected above the natural frequency of additional cancers. In the curative treatment of patients with Hodgkins disease, ionizing radiations are not associated with an increased frequency of leukemias and induced second tumors are no more frequent than following the use of alkylating agents. 4. All second tumors attributed to radiation therapy occur after a latent period of many years and except for leukemia usually are potentially curable. 5. The risks of radiation-induced second cancers are no greater than the risks of operative or anesthetic deaths and these catastrophes are immediate and non-remedial. 6. Therefore, at this time, the potential of radiation-induced cancers should not be a factor in the selection of treatment for patients with cancer. PMID- 2189847 TI - Investigators relate experience with bovine somatotropin. PMID- 2189848 TI - Isolation of Leptospira interrogans serovar bratislava from stillborn and weak pigs in Iowa. AB - Leptospira interrogans serovar bratislava was isolated from a herd of swine in Iowa with a history of stillborn and weak neonatal pigs. Placentas, kidneys, and lungs of stillborn and weak pigs from 3 litters were processed to detect leptospires by use of bacteriologic culture and fluorescent antibody testing. Sera from stillborn and weak pigs were tested to detect agglutinating antibody against leptospires. A low antibody titer against L interrogans serovar bratislava was detected in the sera of stillborn and weak pigs. Small numbers of leptospires were sometimes detected in tissues by use of the fluorescent antibody test. Serovar bratislava was isolated from placentas, stillborn pigs or weak pigs from each of the 3 litters. PMID- 2189849 TI - Differential antibody responses to Corynebacterium pseudotuberculosis in sheep with naturally acquired caseous lymphadenitis. AB - Enzyme-linked immunosorbent assays (ELISA) with Corynebacterium pseudotuberculosis cell wall and bacteria-free supernatant with exotoxin preparations as antigens, and hemolysis inhibition tests were used to detect antibodies in the sera of adult range sheep with naturally acquired caseous lymphadenitis (CL). The extent and severity of lesions were quantitated on the basis of a lesion score, derived from an examination of the carcass (peripheral lymphoid tissue) and viscera (including internal lymphoid tissue) at the time of slaughter. The overall prevalence of C pseudotuberculosis-positive CL lesions in 104 sheep was 31.7%. The cell wall ELISA detected antibodies in 96.9% (32/33) of sheep with C pseudotuberculosis-positive CL lesions. The exotoxin ELISA detected antibodies in 84.8% (28/33) of positive sheep in the same group. Both ELISA resulted in a high number of apparent false-positives, with 64.7% and 49.2%, respectively, positive optical density (OD) values in sheep with no gross CL lesions and no apparent C pseudotuberculosis infection. There was no significant relationship between the extent of lesion development (lesion score) and OD values in both cell wall (r = 0.472) and exotoxin (r = 0.464) ELISA. Similarly, there was no significant relationship between the titer of antitoxin antibodies, as measured by the hemolysis inhibition test, and the extent of disease. These investigations indicate that those ELISA that use crude C pseudotuberculosis antigens are of questionable utility in the field, where C pseudotuberculosis infection is endemic in many sheep populations. Furthermore, these studies suggest that antibodies that are reactive with components of C pseudotuberculosis and that develop in response to infection may have little impact on the recovery of the host. PMID- 2189850 TI - Drug therapy in cats: a therapeutic category approach. AB - The third article of this 4-part series discusses drug therapy in cats by therapeutic category. Specifically, the use of drugs to control infections, pain, fever, inflammation, cancer, and selected parasites is described. In addition, the use of hormonally related drugs and selected miscellaneous drugs in cats is addressed. Drugs emphasized are those for which use in cats is frequently associated with adverse reactions or drugs for which use is limited to illnesses that tend to be unique in cats. PMID- 2189851 TI - What is your diagnosis? Tendinitis of the superficial digital flexor tendon. PMID- 2189852 TI - Proceedings of an International Roundtable on Bovine Spongiform Encephalopathy. PMID- 2189853 TI - Scrapie in France. PMID- 2189854 TI - Septicaemia--the clinical diagnosis. AB - The production and consequences of the components of the state defined as 'clinically significant sepsis', as seen in patients undergoing intensive therapy -fever, shock, respiratory failure and multiple system failure--are complex. The syndrome is not necessarily accompanied by detectable bacteraemia; the effective management cannot wait upon positive blood cultures. Possibilities for more effective intervention include the use of monoclonal antibodies to endotoxin or to tumour necrosis factor, and of prostaglandins to alter the microcirculation. More refined definition of the severe sepsis syndrome will be required before these measures can be fully evaluated. PMID- 2189855 TI - Blood culture technique: current controversies. AB - Currently controversial questions include: what is the optimal volume of blood for culture and which blood culture system is most suitable for the rapid and reliable detection of important pathogens? The author has discussed these topics and recommends the following: (1) At least 10 ml blood should be cultured for each set from an adult but the maximum possible volume, up to 30 ml, should be cultured. This is especially advisable when febrile immunocompromised patients and patients with infective endocarditis are investigated. (2) The best routine system for obtaining rapid and reliable blood culture results involves the use of two aerobic diphasic media and one anaerobic broth for the culture of 20 ml blood per set. Two blind subcultures are recommended during the first 24 h incubation. This conventional system is impracticable for some laboratories that process enormous numbers of blood cultures and for these laboratories the infrared Bactec system is recommended. (3) An additional blood culture method, such as the lysis centrifugation system, should be used together with the routine system when clinical circumstances suggest the need to isolate particular 'difficult organisms' and to facilitate the culture of the maximum volume of blood. (4) It is preferable that the routine system includes one bottle without Liquoid as Liquoid-sensitive organisms may otherwise be inhibited even when gelatin is included in the medium. PMID- 2189856 TI - The causative organisms of septicaemia and their epidemiology. AB - During the 20 years, 1969-88, nearly 4000 episodes of septicaemia were studied prospectively at St. Thomas' Hospital. Forty percent were community-acquired and 60% hospital-acquired. Overall the commonest isolate was Escherichia coli (22%). In community-acquired bacteraemias, Esch. coli, Streptococcus pneumoniae and Staphylococcus aureus accounted for almost 60% of episodes, and the commonest foci of infection were the urinary tract (Esch. coli) and the respiratory tract (Str. pneumoniae). Esch. coli was particularly common in diabetic patients and Str. pneumoniae in alcoholics. In hospital-acquired septicaemia, Esch. coli and Staph. aureus accounted for 40% of episodes, but a further 30% were caused by enterobacteria other than Esch. coli, and Pseudomonas aeruginosa. The commonest foci of infection were the urinary tract, often with catheterization or instrumentation, and intravascular access sites, from which episodes of septicaemia were increasingly caused by coagulase-negative staphylococci. PMID- 2189857 TI - Therapy: the microbiologist's view. AB - Potentially, the clinical microbiologist is able to influence empirical and definitive therapy of bacteraemia. Definitive therapy of the individual can only be affected after the results of routine culture and sensitivity tests are available. Some so-called 'rapid' laboratory techniques enable early identification and sensitivity testing of isolates from blood cultures. Empirical therapy is more difficult to influence, with microbiologists relying on epidemiologically based education of the prescriber or encouragement of him to seek advice at an early stage. Newer, truly rapid methods that do not rely on culture may come to have an impact on individual empirical therapy. Microbiologists acquire information upon which to base their recommendations by a variety of local surveillance measures, from the published literature and (particularly for organisms of infection control significance) through professional contacts with their colleagues in other hospitals. Influence may be exerted on clinicians by direct contact, through manipulation of the content of laboratory reports, or by regular circulation of locally-collected summary data. The assessment of the real impact on bacteraemia of blood culture techniques and microbiological advice is in its infancy, but new data collection and handling methods make this an achievable ideal. PMID- 2189858 TI - Pathogenesis of septicaemia. AB - This review concentrates on two aspects of the pathogenesis of septicaemia. Firstly, those factors that enable bacteria to resist or avoid host defence mechanisms, including opsonization, phagocytosis, intracellular killing and terminal complement lysis of bacterial cell walls, are described. Secondly, the complication of septicaemia by septic shock with reference to the role played by lipopolysaccharide and tumour necrosis factor is reviewed, as are the possible implications for therapy. PMID- 2189859 TI - Therapy: the clinician's view. AB - The therapy of septicaemia often has to be started empirically and the clinician's choice of antibiotic depends upon awareness of data collected by the microbiologist concerning the species and sensitivity of the likely infecting bacteria. There is, however, no unequivocally correct choice and host factors, previous antibiotic use and local formulary recommendations need to be considered. The role of new antibiotics, the potential for cidal agents to be detrimental, the use of antibiotic combinations, the dose and duration of therapy are also still debatable. Even with optimal antibiotic therapy, some patients with septicaemia still die. Several forms of adjunctive therapy have been shown to be unhelpful but developments in immunotherapy hold out some promise. PMID- 2189860 TI - Neurogenesis, control, and functional significance of gasping. AB - Gasps are frequently the first and last breaths of life. Gasping, which is generated by intrinsic medullary mechanisms, differs fundamentally from other automatic ventilatory patterns. A region of the lateral tegmental field of the medulla is critical for the neurogenesis of the gasp but has no role in eupnea. Neuronal mechanisms in separate brain stem regions may be responsible for the neurogenesis of different ventilatory patterns. This hypothesis is supported by the recording of independent respiratory rhythms simultaneously from isolated brain stem segments. Data from fetal and neonatal animals also support gasping and eupnea being generated by separate mechanisms. Gasping may represent the output of a simple but rugged pattern generator that functions as a backup system until the control system for eupnea is developed. Pacemaker elements are hypothesized as underlying the onset of inspiratory activity in gasping. Similar elements, in a different brain stem region, may be responsible for the onset of the eupneic inspiration with neural circuits involving the pons, the medulla, and the spinal cord serving to shape efferent respiratory-modulated neural discharges. PMID- 2189861 TI - Inflation of antishock trousers increases bronchial response to methacholine in healthy subjects. AB - We studied changes in lung volumes and in bronchial response to methacholine chloride (MC) challenge when antishock trousers (AST) were inflated at venous occlusion pressure in healthy subjects in the standing posture, a maneuver known to shift blood toward lung vessels. On inflation of bladders isolated to lower limbs, lung volumes did not change but bronchial response to MC increased, as evidenced by a greater fall in the forced expiratory volume in 1 s (FEV1) at the highest dose of MC used compared with control without AST inflation (delta FEV1 = 0.94 +/- 0.40 vs. 0.66 +/- 0.46 liter, P less than 0.001). Full inflation of AST, i.e., lower limb and abdominal bladder inflated, significantly reduced vital capacity (P less than 0.001), functional residual capacity (P less than 0.01), and FEV1 (P less than 0.01) and enhanced the bronchial response to MC challenge compared with partial AST inflation (delta FEV1 = 1.28 +/- 0.47 liter, P less than 0.05). Because there was no significant reduction of lung volumes on partial AST inflation, the enhanced bronchial response to MC cannot be explained solely by changes in base-line lung volumes. An alternative explanation might be a congestion and/or edema of the airway wall on AST inflation. Therefore, to investigate further the mechanism of the increased bronchial response to MC, we pretreated the subjects with the inhaled alpha 1-adrenergic agonist methoxamine, which has both direct bronchoconstrictor and bronchial vasoconstrictor effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189862 TI - Tracheal smooth muscle responses to upper airway pressure in conscious dogs. AB - We studied the influence of changes in pressure applied to the isolated upper airway of four conscious dogs on tracheal smooth muscle tone and breathing pattern. The dogs were prepared with a permanent side-hole tracheal stoma and were trained to sleep with a snout mask hermetically sealed in place while breathing through a cuffed endotracheal tube inserted distally into the tracheal stoma. Changes in tracheal smooth muscle tone were continuously monitored by measuring the pressure in the water-filled cuff that distended the tracheal airway while pressure changes were introduced in the upper airway independently of breathing. Increases or decreases of upper airway pressure (+/- 10 cmH2O) had little effect on tracheal airway smooth muscle tone. In contrast, an oscillating pressure wave at 30 Hz and +/- 3 cmH2O amplitude (or -3 to -7 cmH2O amplitude) caused a marked increase in tracheal airway smooth muscle tone. An elevated tracheal airway tone could be maintained over many minutes when the oscillating pressure stimulus was pulsed so that there was a cycle of 0.5 s on, 0.5 s off. This stimulus did not change the functional residual capacity but resulted in coughing, swallowing, or sighing in 54% of the tests. In the remaining tests, the pressure stimulus produced a rapid, shallow, and erratic breathing pattern. The tracheal airway constrictor response (but not the ventilatory response) was completely abolished by intravenous atropine. We suggest that upper airway vibration is a potentially powerful mechanism of reflex airway smooth muscle constriction. PMID- 2189863 TI - Pathogenesis of pulmonary edema associated with intracisternal endotoxin in dogs. AB - To examine the role of central nervous system injury in the pathogenesis of pulmonary edema, we injected Escherichia coli endotoxin (5 mg/kg) into the cisterna magna of six dogs (group E) and compared, over 4 h, both the pulmonary edema and cerebrospinal fluid (CSF) abnormalities with those in six control dogs (group C). In group E, intracisternal endotoxin raised intracranial pressure from 21 +/- 6 to 38 +/- 8 cmH2O (P less than 0.001), CSF total protein from 18 +/- 6 to 54 +/- 19 mg/dl (P less than 0.001), and CSF malondialdehyde from 0.12 +/- 0.11 to 0.61 +/- 0.35 nmol/ml (P less than 0.05); all were unchanged in group C. When the pulmonary wedge pressure was maintained at 10 mmHg by fluid infusion, extravascular thermal volume in group E increased from 7.2 +/- 1.2 to 12.0 +/- 2.7 ml/kg (P less than 0.005) at 4 h when the excised lungs weighed 13.6 +/- 1.5 g/kg; in group C, extravascular thermal volume did not increase, and the excised lungs weighed less (10.8 +/- 1.3 g/kg, P less than 0.05) than those in group E. The dry weights of the lungs were not different between groups, and the alveolar lining fluid-to-plasma albumin ratio in both groups remained low, 0.1-0.2. Fluid infusion in group E (9.2 +/- 2.9 liters) caused colloid oncotic pressure to decrease 4.5 +/- 2.8 mmHg; colloid oncotic pressure fell less (0.8 +/- 1.9 mmHg, P less than 0.001) in group C as less fluid (2.2 +/- 1.5 liters, P less than 0.001) was required to maintain pulmonary wedge pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189864 TI - Inductance plethysmography measurement of CPAP-induced changes in end-expiratory lung volume. AB - The respiratory inductance plethysmograph (RIP) has recently gained popularity in both the research and clinical arenas for measuring tidal volume (VT) and changes in functional residual capacity (delta FRC). It is important however, to define the likelihood that individual RIP measurements of VT and delta FRC would be acceptably accurate (+/- 10%) for clinical and investigational purposes in spontaneously breathing individuals on continuous positive airway pressure (CPAP). Additionally, RIP accuracy has not been compared in these regards after calibration by two commonly employed techniques, the least squares (LSQ) and the quantitative diagnostic calibration (QDC) methods. We compared RIP with pneumotachographic (PTH) measurements of delta FRC and VT during spontaneous mouth breathing on 0-10 cmH2O CPAP. Comparisons were made after RIP calibration with both the LSQ (6 subjects) and QDC (7 subjects) methods. Measurements of delta FRC by RIPLSQ and RIPQDC were highly correlated with PTH measurements (r = 0.94 +/- 0.04 and r = 0.98 +/- 0.01 (SE), respectively). However, only an average of 30% of RIPQDC determinations per subject and 31.4% of RIPLSQ determinations per subject were accurate to +/- 10% of PTH values. An average of 55.2% (QDC) and 68.8% (LSQ) of VT determinations per subject were accurate to +/- 10% of PTH values. We conclude that in normal subjects, over a large number of determinations, RIP values for delta FRC and VT at elevated end-expiratory lung volume correlate well with PTH values. However, regardless of whether QDC or LSQ calibration is used, only about one-third of individual RIP determinations of delta FRC and one-half of two-thirds of VT measurements will be sufficiently accurate for clinical and investigational use. PMID- 2189865 TI - Late-phase pulmonary reactions. PMID- 2189866 TI - Effect of ketotifen on childhood asthma: a double-blind study. AB - Ketotifen was administered orally, for 3 months, to 40 children aged 3-14 years with chronic extrinsic asthma of moderate severity in a double-blind placebo controlled study. A significant clinical improvement with concomitant reduction of antiasthmatic drugs was found in the group receiving the active drug compared with the placebo group (p less than 0.05). The continued administration of ketotifen in an open study to a group of 21 children comprised of patients belonging to both groups (active-placebo) for a period of 15-18 months resulted in disappearance of symptoms in 10 children (47.6%) and moderate improvement in 7 (33.3%). PMID- 2189867 TI - A case report of naltrexone treatment of self-injury and social withdrawal in autism. AB - The endogenous opiate release theory of self-injurious behavior (SIB) was investigated through double-blind placebo-controlled administration of naltrexone hydrochloride (Trexan) to a 14-year-old autistic and mentally retarded male for treatment of severe SIB. Results yielded a marked decrease in SIB during two phases of active drug treatment, though SIB did not revert to originally observed placebo levels during a second placebo phase. An increase in social relatedness also was observed during phases of active drug treatment. Opiate theories of self injury and the possible interrelationship of self-injury with pituitary-adrenal arousal and with social relatedness are discussed. PMID- 2189868 TI - Borderline disorders of childhood: an overview. AB - This selected review considers children classified as "borderline" and focuses on two broad categories: Borderline personality disorder/borderline spectrum and schizotypal personality disorder/autism/schizophrenia spectrum classifications. Clinical descriptions, biological correlated, delimitation from other disorders, outcome, family studies, hypothesized etiologies, therapeutic considerations, and response to treatment are presented for each. Data support the subclassification of the heterogeneous groupings of borderline children into at least the two categories, and their differentiation from each other and from other clinical disorders in the population. Overlap across the borderline categories exists for individual children. The nature and shortcomings of relevant studies are described, the need for scientifically based research championed, and a differential approach to directive treatment of borderline children advocated. Further subclassification of borderline disorders should result in more cost effective diagnosis and treatment. PMID- 2189869 TI - Core symptoms of posttraumatic stress disorder unimproved by alprazolam treatment. AB - The authors report a random-assignment, double-blind crossover trial comparing alprazolam and placebo in posttraumatic stress disorder (PTSD). Ten patients fulfilling DSM-III criteria for PTSD completed 5 weeks of treatment on each agent. Improvement in anxiety symptoms was significantly greater during alprazolam treatment but modest in extent. Symptoms specific to PTSD were not significantly altered. The impact of nonspecific symptomatic effects on the outcome of drug trials in PTSD is considered. PMID- 2189870 TI - Alexithymia among Vietnam veterans with posttraumatic stress disorder. AB - The authors studied 227 inpatients from a large Veterans Administration Medical Center to evaluate whether alexithymia is associated with posttraumatic stress disorder (PTSD) and to assess the validity of the Minnesota Multiphasic Personality Inventory (MMPI) alexithymia scale. Three groups--a carefully diagnosed PTSD group (N = 76), an alcohol abuse group (N = 76), and a general psychiatric group (N = 75)--were given a battery of psychological tests, including the MMPI, the Millon Clinical Multiaxial Inventory, and the Beck Depression Inventory, along with several cognitive measures. PTSD veterans were also evaluated on psychophysiologic indices (including a stressor) and on their subjective ratings to these indices. Results showed that alexithymia was more characteristic of PTSD patients than of the other groups. Also, alexithymia was inversely related to heart rate. Alexithymia was not significantly correlated with the subjective experience of stressors. The authors discuss the importance of the construct of alexithymia among PTSD patients and recommend the use of the alexithymia scale for these patients. The independence of this measure from the psychophysiologic condition of hyperarousal and the subjective experience of this state were also addressed. PMID- 2189871 TI - Imipramine equivalents. PMID- 2189872 TI - Problems associated with the diagnosis of depression. AB - Depressive disorders are both common and often easily treated. However, a major stumbling block in the care of these patients remains the recognition and accurate diagnosis of these conditions. The author summarizes commonly encountered pitfalls in the diagnosis of these patients and potential remedies. Issues of subtyping depression based on cross-sectional evaluation of the symptom picture, as well as prior course of illness, anticipated treatment response, and anticipated prognosis, are discussed. PMID- 2189873 TI - Psychosocial aspects of depression and the role of psychotherapy. AB - The psychosocial aspects of depression are considered with respect to psychological factors (i.e., thinking, personality, coping style) and social factors (i.e., family, relationships, employment, life events). Etiologic/mechanistic controversies are only acknowledged, as the purpose of this review is to underscore the wide variety of psychosocial complications that can occur during a depressive episode. The potential roles of psychotherapy in the treatment of mood disorders are considered. Results regarding the efficacy of behavioral therapy, cognitive therapy, and interpersonal psychotherapy in the treatment of unipolar, nonpsychotic, adult depressed outpatients are summarized. PMID- 2189874 TI - Depression and chronic medical illness. AB - Major depression is the most common clinical problem primary care physicians are called upon to diagnose and treat. Depression is associated with high medical care utilization, amplification of somatic symptoms and disability, poor self care and adherence to medical regimens, and increased morbidity and mortality from medical illness. Despite the high prevalence and the maladaptive effects of major depression on patients' lives, this affective illness is often not accurately diagnosed or effectively treated. Double-blind, placebo-controlled studies have increasingly demonstrated efficacy of the antidepressant agents in primary care patients, patients with chronic pain, and patients with comorbidity- chronic medical illness and major depression. PMID- 2189875 TI - Relapse and recurrence in unipolar major depression: short-term and long-term approaches. AB - Relapse and recurrence following successful short-term treatment of major depression are common and vexing clinical problems. The risk of relapse and recurrence is reviewed, as is evidence pertaining to pharmacologic and psychosocial strategies for continuation and maintenance therapy. Up to 6 months' continuation treatment following short-term treatment response is recommended routinely for virtually all patients. Based on available evidence, a more prolonged course of maintenance pharmacotherapy is strongly recommended for patients with residual symptomatology and/or a past history of chronicity or multiple depressive episodes. Further research is necessary to identify the specific indications for combining psychotherapy and pharmacotherapy. PMID- 2189877 TI - The role of rating scales in the identification and management of the depressed patient in the primary care setting. AB - The author conducted a review of the literature for reported prevalence of depression in primary care settings. Studies that provided data on both standardized interview and self-ratings were included. Reported prevalences from six studies ranged from 6% to 17%. Based on the results of 904 questionnaires administered at continuing medical education meetings held in 11 cities across the United States, primary care physicians estimated that 14% of their patients have a component of depression. To evaluate the usefulness of patient self-rating depression scales in the family practice setting, studies were reviewed where the patients' physicians were either notified or not notified of the results of a screening in which the Zung Self-Rating Depression Scale was used. In six published studies, results showed that notified physicians were able to increase their ability to recognize depression by 2.5-fold to 25-fold. PMID- 2189876 TI - The cost of antidepressant drug therapy failure: a study of antidepressant use patterns in a Medicaid population. AB - Paid claims data from the California Medicaid (Medi-Cal) program were used to examine the utilization of antidepressants and to estimate the costs of antidepressant treatment failure for patients with major depressive disorders (MDD). Data for 6713 new patient episodes of antidepressant therapy were available for the analysis; over 45% of these patients never achieved a minimum daily dose of antidepressants indicative of treatment for depression and were excluded from further analysis. That left a possible depression patient population of 3664 patients of which 2344 patients had a minimum of 1 full year of post-episode data for analysis. Only 81 patients (3.5%) displayed antidepressant use patterns consistent with the successful treatment of MDD; 296 patients (12.6%) displayed use patterns suggestive of antidepressant treatment failure. The remaining 1967 (84%) patients could not be clearly classified; they were either (1) patients being treated for problems other than MDD, (2) MDD patients who were being prescribed subtherapeutic doses by their physician due to side effects or other reasons, (3) MDD patients who were noncompliant for a variety of reasons, or (4) MDD patients who had prematurely terminated antidepressant therapy. Multivariate regression analysis was used to estimate the costs associated with MDD treatment failure. These analyses indicated that MDD treatment failure resulted in increased costs of approximately $1043 in the first post-episode year (p less than .10). These increased costs were primarily due to higher hospital costs ($921, p less than .05), while drug costs were reduced by $222 (p less than .001). PMID- 2189878 TI - The comorbidity of anxiety and depression in general medical patients: a longitudinal study. AB - In a general medical clinic setting, 880 patients were screened for depression by using the Diagnostic Interview Schedule version of the DSM-III and the Zung Self Rating Depression Scale (SDS), as well as the Zung Self-Rating Anxiety Scale (SAS). Based on a morbidity cutoff index of 50 on the SDS and a positive DIS for depression, 112 patients (13%) were found to have a depressive disorder. The SDS showed a 97% sensitivity, a 63% specificity, and an 82% correct classification of depressed and nondepressed control patients. Based on the SDS results and SAS results when anxiety was considered present at a moderate severity level, the comorbidity of anxiety and depression was 67%. Depressed patients were followed for 1 year during which time they were retested with the SDS and SAS at five time points (6 weeks and quarterly). Fifty-one patients who met the criterion of a decrease of greater than or equal to 12 points in the SDS index were assigned to the improved group, 23 who met the criterion of an increase of greater than or equal to 12 points were assigned to the worse group, and 36 patients were assigned to the no-change group. Depressed patients who improved showed a significant decrease in anxiety based on SAS change scores; depressed patients who worsened showed a significant increase in their anxiety index. The decrease in the anxiety index of patients in the no-change group was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189879 TI - The influence of hydrogel functional groups on cell behavior. AB - This study provides information on the behavior of macrophages on the surface of the subcutaneously implanted hydrogel strips. Hydrogel containing -OH, -CO-NH-, and (CH3)2N- groups induced a spreading of macrophages on the implants. The materials containing -SO3H groups slightly, and materials containing -COOH groups more intensively, inhibited spreading of the macrophages. The fusion of macrophages into multinucleate cells was inhibited on the surface of materials containing acidic groups (-SO3H, -COOH) and increased on the hydrogels containing 30 mol% of alkaline (CH3)2N- groups in comparison with hydrogels containing -OH or -CO -NH- groups. The differences of the behavior of macrophages on the surface of individual types of hydrogels are probably independent on the adsorption of plasma fibronectin onto the hydrogels. The correlation between the macrophages spreading and fusion and surface charge of the hydrogel implant can be hypothetically explained by electrostatic interaction between macrophages cell membrane and implant. PMID- 2189880 TI - The histological effects of the implantation of different sizes of polyethylene particles in the rabbit tibia. AB - This study examines the histological effects of different sizes of polyethylene particles implanted into the rabbit tibia. Seventeen mature New Zealand white female rabbits were allocated into three groups. Group 1 (5 rabbits) received polyethylene particles averaging approximately 16 microns in diameter, implanted into the right proximal tibia through a drill hole. Group 2 (5 animals) received particles averaging 26 microns, and Group 3 (7 rabbits) received particles averaging 67 microns. The left tibia was drilled but not implanted. Animals were sacrificed after 16 weeks. Histological analysis disclosed decreased hematopoietic activity within the left tibial drill hole. In all groups, the right tibia demonstrated positively birefringent polyethylene particles surrounded by, and within (smaller particles), histiocytes and giant cells in a fibrous tissue stroma. Statistical analysis disclosed more fibrocytes and less marrow cells at the interface of Group 3 (largest particles) compared to Group 1 and 2. Larger polyethylene particles, being less readily phagocytosed, appear to produce more fibrous encapsulation, compared to particles of a smaller size. The histological reaction stimulated by the different sizes of polyethylene particles resembled the membrane surrounding loose joint arthroplasties in humans. PMID- 2189881 TI - Role of galaptin in ovarian carcinoma adhesion to extracellular matrix in vitro. AB - Immunohistochemical studies indicated that galaptin is a major protein of ovarian carcinoma cells present in patient effusions and it is distributed throughout the cytoplasm. Enzyme-linked immunoadsorbent assay (ELISA) and immunoprecipitation experiments demonstrated that galaptin is also a major protein of the A121 ovarian carcinoma cell line, constituting less than or equal to 1% of extractable protein bound by DEAE Sephacel. Western blot analyses revealed that the galaptin present in ovarian carcinoma consists of a 14.5 KD subunit. Ovarian carcinoma and mesothelial cells isolated from patient effusions display surface receptors for galaptin with an apparently greater density of receptors present on the carcinoma cells. A121 cells also display surface receptors for galaptin: binding sites/cell = 3 X 10(8) and Ka = 1.2 X 10(9) M-1. The presence of galaptin in bovine corneal endothelial cells (BCEC) and BCEC-derived extracellular matrix (ECM) was demonstrated by ELISA. Of the total ECM-bound galaptin, about 75% appears to be insoluble in phosphate-buffered saline (PBS) lactose. ECM was also found to contain abudnant receptors for galaptin. Treatment of ECM with lactose increased the apparent galaptin receptor density:binding sites/cm2 = 7 X 10(13) and Ka = 2.6 X 10(9) M-1. Pretreatment of A121 cells with galaptin inhibited adhesion to ECM. The addition of exogenous galaptin to ECM had variable effect on cell adhesion. The data presented here suggest that early adhesion events may be carbohydrate-specific involving interaction between ECM-bound galaptin and cell surface galaptin receptors. PMID- 2189882 TI - Clinical Review 9: Management of asymptomatic hyperparathyroidism. PMID- 2189883 TI - Reduced postprandial skeletal muscle blood flow contributes to glucose intolerance in human obesity. AB - While it is well accepted that the disposal of an oral glucose load (OGL) occurs primarily in skeletal muscle, the mechanisms by which this occurs are not completely elucidated. Glucose uptake (GU) in skeletal muscle follows the Fick principal, such that GU equals the products of the arteriovenous glucose difference (AVGd) across and the blood flow (BF) into muscle. It is widely believed that in the postprandial period both insulin and glucose increase GU by increasing the AVGd; however, a role for increments in BF in the disposal and tolerance of an OGL has not been established. To investigate this issue, whole body GU (isotope dilution), leg GU (leg balance technique), leg BF, and cardiac index (CI) were measured after an overnight fast and over 180 min after an OGL (1 g/kg) in 8 lean (ln) and 8 obese (ob) subjects [mean +/- SEM age, 36 +/- 2 vs. 37 +/- 2 yr (P = NS) and 60 +/- 1 vs. 99 +/- 5 kg (P less than 0.01), respectively]. Serum glucose levels were higher in the ob than in the ln subjects between 100 and 160 min, indicating reduced glucose tolerance. Fasting and post-OGL serum insulin levels were 2- to 3-fold higher in ob vs. ln at all times, indicating insulin resistance. Peak (40-80 min) incremental whole body GU above baseline was 32% lower in ob vs. ln, (P less than 0.05). Peak femoral AVGd was not different between ob and ln (0.55 +/- 0.16 vs. 0.66 +/- 0.14 mmol/L; P = NS). Peak leg BF increased 36% over baseline in ln (0.328 +/- 0.052 to 0.449 +/- 0.073 L/min; P less than 0.05), while ob subjects displayed no change in leg BF from baseline. Consequently, peak leg GU was 44% lower in ob vs. ln (P less than 0.05). CI increased 24% from baseline at 60 min in ln (P less than 0.05), but was unchanged in ob. In summary, after an OGL 1) femoral AVGd increases in both ln and ob subjects, but skeletal muscle BF and CI increase in ln only; 2) since peak femoral AVGd values were similar in ln and ob, differences in peak leg GU and (by inference) whole body GU are largely due to reduced BF to insulin-sensitive tissues; and 3) hemodynamics play an important role in the physiological disposal of an OGL, and therefore, hemodynamic defects can potentially contribute to reduced glucose tolerance and insulin resistance. PMID- 2189884 TI - A modified protocol for estimation of insulin sensitivity with the minimal model of glucose kinetics in patients with insulin-dependent diabetes. AB - An exogenous insulin administration-modified, frequently sampled iv glucose tolerance test (FSIGT) for application in insulin-dependent diabetic patients (IDDM) to allow for estimation of insulin sensitivity (SI) and glucose effectiveness (SG) with Bergman's minimal model of glucose kinetics was investigated. An insulin infusion protocol (either 4 or 8 mU/min.kg from 20-25 min) was compared to the standard tolbutamide-modified (300 mg at 20 min) FSIGT in normal control subjects. SI and SG were not different for the insulin infusion and tolbutamide-modified protocols [SI, 2.8 +/- 0.4, 3.6 +/- 0.6, and 2.5 +/- 0.5 X 10(4) min1/(microU/mL), respectively]. SI and SG were quantified in insulin requiring newly diagnosed IDDM and in noninsulin-requiring IDDM in clinical remission with the exogenous insulin administration protocol. Both SI and SG were reduced in newly diagnosed IDDM compared to normal controls (by 64% and 40%, respectively). SI was normalized in IDDM in clinical remission despite a continued poor insulin secretory response to both glucose and tolbutamide. Although SI was normal in patients in clinical remission, SG remained reduced (by 65%) compared to that in normal controls. In conclusion, our results demonstrate that modification of the FSIGT with the exogenous administration of insulin allows for estimation of insulin sensitivity and glucose effectiveness in IDDM patients. Comparison to the standard protocol in normal subjects suggests that this results in valid measurements of insulin sensitivity and glucose effectiveness. Results of the application of this protocol in IDDM were consistent with previous observations that insulin sensitivity is reduced in poorly controlled IDDM and normalized in well controlled patients. Glucose effectiveness was found to be reduced in all IDDM subjects regardless of the degree of control. PMID- 2189885 TI - Effects of weight loss and reduced hyperglycemia on the kinetics of insulin secretion in obese non-insulin dependent diabetes mellitus. AB - Impairment in pancreatic production of insulin, a cardinal feature of noninsulin dependent diabetes mellitus (NIDDM), was quantified and the kinetics of insulin secretion characterized in six obese individuals with NIDDM before and after weight loss (18.0 +/- 3.0 kg, mean +/- SEM) using a validated mathematical model that employs C-peptide as a marker of the in vivo rate of insulin secretion. The metabolic clearance of C-peptide, assessed by decay analysis after bolus injection of biosynthetic human C-peptide, was not changed by weight loss (0.143 +/- 0.009 L/min.m2 vs. 0.137 +/- 0.010 L/min.m2). Kinetic parameters from each individual's decay curve before and after weight loss were used to derive accurate rates of secretion during the basal (postabsorptive) state, an oral glucose tolerance test and two hyperglycemic clamps. Basal rates of insulin secretion declined 20 +/- 5 pmol/min.m2 (96 +/- 15 to 76 +/- 15 pmol/min.m2, P less than 0.05) concomitant with decreases of 6.9 +/- 0.9 mmol/L in fasting serum glucose (13.7 +/- 1.0 to 6.8 +/- 0.7 mmol/L, P less than 0.05), 60 +/- 14 pmol/L in serum insulin (134 +/- 30 to 74 +/- 15 pmol/L, P less than 0.05), and 0.15 +/- 0.03 pmol/ml in plasma C-peptide (0.67 +/- 0.11 to 0.52 +/- 0.08 pmol/ml, P less than 0.05) concentrations. As expected, weight loss resulted in improved glucose tolerance as measured by the glycemic profiles during the oral glucose tolerance test (P less than 0.05 analysis of variance). The insulin secretory response before weight loss showed a markedly reduced ability to respond appropriately to an increase in the ambient serum glucose. After weight loss, the pancreatic response was more dynamic (P less than 0.05, analysis of variance) and parralleled the moment-to-moment changes in glycemia. Insulin production above basal doubled (11.2 +/- 3.2 to 24.5 +/- 5.8 nmol/6h.m2, P less than 0.05) and peak rates of insulin secretion above basal tripled (55 +/- 16 to 157 +/- 32 pmol/min/m2, P less than 0.05). To assess the beta-cell response to glucose per se and the changes associated with weight reduction, two hyperglycemic clamps were performed at steady state glucose levels in the range characteristic of individuals with severe NIDDM. At a fixed glycemia of 20 mmol/L, average rates of insulin secretion increased almost 2-fold with treatment (161 +/- 41 to 277 +/- 60 pmol/min.m2, P less than 0.05). At an increment of 6 mmol/L glucose above prevailing fasting glucose levels, the average rate of insulin secretion increased 53% (120 +/- 21 to 183 +/- 39 pmol/min.m2, P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2189886 TI - Pulsatile versus continuous intravenous administration of growth hormone (GH) in GH-deficient patients: effects on circulating insulin-like growth factor-I and metabolic indices. AB - The episodic and pulsatile nature of GH secretion in normal man is well established. Studies in hypophysectomized rats have indicated that pulsatile administration of GH is superior to continuous infusion in promoting growth, but similar studies have not yet been conducted in human subjects. We compared three different iv GH administration schedules in six GH-deficient patients. They were hospitalized three times for 44 h on three occasions, separated by at least 4 weeks without GH treatment. On each occasion they received 2 IU GH, administered iv as either 1) two boluses (at 2000 and 0200 h), 2) eight boluses (at 3-h intervals starting at 2000 h), or 3) a continuous (2000-0200 h) infusion. Serum insulin-like growth factor-I (IGF-I) after eight boluses and that after continuous infusion were almost identical, with a steep increase reaching a peak at 2000-2400 h, followed by a steady decline. The total areas under the curve, expressed as mean levels (micrograms per L), were 147.6 +/- 11.8 (eight boluses) and 151.2 +/- 8.9 (infusion; P = NS). The change with time in IGF-I after the two bolus regimen differed significantly from that in the other studies (P less than 0.001), displaying only a modest increase, as also reflected in a smaller area under the curve of serum IGF-I (125.3 +/- 8.7 micrograms/L; P less than 0.05). No differences in blood glucose, serum insulin, or plasma glucagon were observed when comparing the three studies. Both blood glucose and serum insulin tended to be elevated during the second night of each study. Almost identical fluctuations were recorded in lipid intermediates in the three studies, with nightly elevations being more pronounced on the first night. Alanine and lactate exhibited nearly identical patterns in the three studies and were characterized by low nocturnal levels. These data indicate that small but frequent iv boluses and continuous infusion of GH are equally effective in generating an increase in IGF-I in GH-deficient patients, whereas the same amount of GH given as two large boluses results in a significantly smaller increase in IGF-I. This could mean that a prolongation of the period during which serum GH is above zero in GH treated subjects is just as essential as pulsatility for the growth-promoting effects of the hormone. PMID- 2189887 TI - The modified minimal model: application to measurement of insulin sensitivity in children. AB - The modified minimal model (MMM), a recently introduced method that assesses insulin sensitivity (SI) by a computed mathematical analysis of the relation between the change in insulin and glucose clearance after a bolus of iv glucose, followed 20 min later by a bolus of tolbutamide, has been standardized in adults, but this method has not been validated in children. We performed an abbreviated 90-min MMM test in 50 children who were siblings of patients with insulin dependent diabetes mellitus and 7 healthy adult volunteers and compared the results to the standard 180-min MMM test in 11 of these subjects. The cohort consisted of 29 prepubertal children [16 males and 13 females; 8.7 +/- 2.0 (mean +/- SEM) yr old]; 16 pubertal children defined as less than 17 yr of age and Tanner stage 2-5 (8 males and 8 females; 13.4 +/- 1.8 yr old), and 12 postpubertal subjects (7 males and 5 females; 18.2 +/- 0.9 yr old), with no significant difference in the weight for length index (WLI) among the 3 groups and with sera of all subjects negative for islet cell antibodies and insulin autoantibodies. The test procedure consisted of 3 baseline blood samples over 30 min, followed at zero time by 0.3 g/kg 25% dextrose infused iv over 1 min and an iv injection of tolbutamide (5 mg/kg) 20 min later; sequential blood samples for glucose and insulin measurements were withdrawn from zero time until completion 90 or 180 min later. In the 11 subjects who underwent both the standard and the abbreviated tests, there was no significant difference between the SI estimated by the 2 methods provided that glucose and insulin values were interpolated at 180 min during the computer calculations of the abbreviated test. Using the 90 min abbreviated test, the SI of the pubertal subjects (2.92 +/- 0.45) was markedly less than that of the prepubertal subjects (6.57 +/- 0.45; P = 0.0001). While the postpubertal group value of 4.63 +/- 0.86 was significantly higher than that of the pubertal group (P = 0.0001), the pre- and postpubertal groups remained significantly different (P = 0.0001). The 10 obese subjects with WLI greater than 120% had a lower SI (3.5 +/- 0.53) than the 47 nonobese subjects with WLI less than 120% (SI = 5.48 +/- 0.42; P less than 0.04), and there was a negative correlation between SI and WLI. None of the study subjects experienced symptomatic hypoglycemia during the test.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2189888 TI - Growth hormone requirement for a normal human adipocyte glucose carrier function. AB - One of the most prominent actions of insulin is stimulation of the glucose carrier in different cell types, especially adipose cells. However, the exact mechanism of the mode of action of insulin, between receptor binding and stimulation of glucose transport, is not understood in detail. We have shown earlier, that GH plays an important role in the control of the insulin-sensitive glucose carrier system in rat fat cells. In this study, we measured glucose transport in fat cells of normal probands, GH-deficient (GHD) and GH-treated GHD patients. From sc fat tissue biopsies of three GHD patients, fat cells were isolated after digestion with collagenase. In normal fat cells, basal glucose transport was slow (t/2 = 2.5 min) and stimulated by insulin (t/2 = 0.8 min), as expected. In fat cells of GHD patients glucose transport was maximal already in the basal state (t/2 = 0.8 min) without an additional effect of insulin. After GH administration during several months to GHD patients, glucose transport was again slow in the basal state (t/2 = 3.2 min) and could be stimulated by insulin (t/2 = 0.7 min). These results confirm our earlier findings in rat adipocytes for human adipocytes: GH in vivo is responsible for a glucose transport-limiting factor in the plasma membrane that restricts basal glucose transport and is acutely inhibited by insulin resulting in enhanced glucose transport. These results demonstrate the physiological importance of GH for a normal function of the insulin transmembrane signaling system in fat tissue and indicate a possible benefit of GH administration in adult GHD patients. PMID- 2189889 TI - Relaxin stimulates the synthesis and release of prorenin from human decidual cells: evidence for autocrine/paracrine regulation. AB - Porcine relaxin caused a time- and concentration-dependent increase in the release of renin from decidual cells cultured over a 96 h period. The increase in renin release occurred 24-48 h after exposure and was maximal at 48-72 h. Half maximal stimulation occurred at a relaxin concentration of 5 ng/ml, and maximal stimulation (250-270%) occurred at concentrations greater than or equal to 10 ng/ml. At each time, greater than 95% of the renin released into the medium was in the form of prorenin. The stimulation of renin release was paralleled by a stimulation of cellular renin content and was completely inhibited by cycloheximide, indicating that relaxin also stimulated renin synthesis. Since renin is present in both cytotrophoblast and decidual cells, these results suggest a paracrine and/or autocrine relationship between relaxin- and prorenin secreting cells. PMID- 2189890 TI - Effects of Escherichia coli hemolysin on human monocytes. Cytocidal action and stimulation of interleukin 1 release. AB - This study reports on the potent cytocidal and interleukin-1 releasing properties of Escherichia coli hemolysin (ECH) on human monocytes. Nanomolar concentrations of purified ECH (250-2,000 ng/ml) caused rapid and irreversible depletion of cellular ATP to levels below 20% of controls within 60 min. Subcytocidal doses (10-200 ng/ml) of ECH induced rapid release within 60-120 min of large amounts of interleukin 1 beta (IL-1 beta) from cultured monocytes. IL-1 beta release occurred in the presence of actinomycin D and cycloheximide, and was thus probably due to processing and export of intracellular IL-1 beta precursor. Incubation of toxin-producing E. coli at ratios of only 0.3-3 colony-forming units per monocyte evoked approximately 50% depletion of total cellular ATP within 90 min. Toxin producers also stimulated synthesis and release of large amounts of interleukin 1, but not of tumor necrosis factor within the same time span. In contrast, non-toxin producers caused neither cell death nor rapid interleukin 1 release. Stimulation of rapid interleukin 1 release coupled with potent cytocidal effects on cells of monocytic origin may represent pathogenetically significant events incurred by bacterial strains that produce ECH and related cytolysins. PMID- 2189891 TI - Relative contribution of glycogen synthesis and glycolysis to insulin-mediated glucose uptake. A dose-response euglycemic clamp study in normal and diabetic rats. AB - To examine the relationship between plasma insulin concentration and intracellular glucose metabolism in control and diabetic rats, we measured endogenous glucose production, glucose uptake, whole body glycolysis, muscle and liver glycogen synthesis, and rectus muscle glucose-6-phosphate (G-6-P) concentration basally and during the infusion of 2, 3, 4, 12, and 18 mU/kg.min of insulin. The contribution of glycolysis decreased and that of muscle glycogen synthesis increased as the insulin levels rose. Insulin-mediated glucose disposal was decreased by 20-30% throughout the insulin dose-response curve in diabetics compared with controls. While at low insulin infusions (2 and 3 mU/kg.min) reductions in both the glycolytic and glycogenic fluxes contributed to the defective tissue glucose uptake in diabetic rats, at the three higher insulin doses the impairment in muscle glycogen repletion accounted for all of the difference between diabetic and control rats. The muscle G-6-P concentration was decreased (208 +/- 11 vs. 267 +/- 18 nmol/g wet wt; P less than 0.01) compared with saline at the lower insulin infusion, but was gradually increased twofold (530 +/- 16; P less than 0.01 vs. basal) as the insulin concentration rose. The G 6-P concentration in diabetic rats was similar to control despite the reduction in glucose uptake. These data suggest that (a) glucose transport is the major determinant of glucose disposal at low insulin concentration, while the rate limiting step shifts to an intracellular site at high physiological insulin concentration; and (b) prolonged moderate hyperglycemia and hypoinsulinemia determine two distinct cellular defects in skeletal muscle at the levels of glucose transport/phosphorylation and glycogen synthesis. PMID- 2189892 TI - Three-dimensional intracellular calcium gradients in single human burst-forming units-erythroid-derived erythroblasts induced by erythropoietin. AB - We have previously shown that the intracellular free Ca2+ increase induced by erythropoietin is likely related to differentiation rather than proliferation in human BFU-E-derived erythroblasts (1989. Blood. 73:1188-1194). Since cell differentiation involves transcription of specific regions of the genome, and since nuclear endonucleases responsible for single strand DNA breaks observed in cells undergoing differentiation are Ca2+ dependent, we investigated whether the erythropoietin-induced calcium signal is transmitted from cytosol to nucleus in this study. To elucidate subcellular Ca2+ gradients, the technique of optical sectioning microscopy was used. After determining the empirical three-dimensional point spread function of the video imaging system, contaminating light signals from optical planes above and below the focal plane of interest were removed by deconvolution using the nearest neighboring approach. Processed images did not reveal any discernible subcellular Ca2+ gradients in unstimulated erythroblasts. By contrast, with erythropoietin stimulation, there was a two- to threefold higher Ca2+ concentration in the nucleus compared to the surrounding cytoplasm. We suggest that the rise in nuclear Ca2+ may activate Ca2(+)-dependent endonucleases and initiate differentiation. The approach described here offers the opportunity to follow subcellular Ca2+ changes in response to a wide range of stimuli, allowing new insights into the role of regional Ca2+ changes in regulation of cell function. PMID- 2189893 TI - Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance. AB - Obesity is characterized by decreased rates of skeletal muscle insulin-mediated glucose uptake (IMGU). Since IMGU equals the product of the arteriovenous glucose difference (AVGd) across muscle and blood flow into muscle, reduced blood flow and/or tissue activity (AVGd) can lead to decreased IMGU. To examine this issue, we studied six lean (weight 68 +/- 3 kg, mean +/- SEM) and six obese (94 +/- 3 kg) men. The insulin dose-response curves for whole body and leg IMGU were constructed using the euglycemic clamp and leg balance techniques over a large range of serum insulin concentrations. In lean and obese subjects, whole body IMGU, AVGd, blood flow, and leg IMGU increased in a dose dependent fashion and maximal rates of all parameters were reduced in obese subjects compared to lean subjects. The dose-response curves for whole body IMGU, leg IMGU, and AVGd were right-shifted in obese subjects with an ED50 two- to threefold higher than that of lean subjects for each parameter. Leg blood flow increased approximately twofold from basal 2.7 +/- 0.2 to 4.4 +/- 0.2 dl/min in lean, P less than 0.01, and from 2.5 +/- 0.3 to 4.4 +/- 0.4 dl/min in obese subjects, P less than 0.01. The ED50 for insulin's effect to increase leg blood flow was about fourfold higher for obese (957 pmol/liter) than lean subjects (266 pmol/liter), P less than 0.01. Therefore, decreased insulin sensitivity in human obesity is not only due to lower glucose extraction in insulin-sensitive tissues but also to lower blood flow to these tissues. Thus, in vivo insulin resistance can be due to a defect in insulin action at the tissue level and/or a defect in insulin's hemodynamic action to increase blood flow to insulin sensitive tissues. PMID- 2189894 TI - Double minutes arise from circular extrachromosomal DNA intermediates which integrate into chromosomal sites in human HL-60 leukemia cells. AB - Amplification of oncogenes has been found to be an important prognostic factor in behavior of patients' malignancies. In this study we have used new gel electrophoresis techniques to follow the location of amplified c-myc oncogene sequences in HL-60 promyelocytic leukemia cells. In passages 46-62 of the cells, the cells contain amplified c-myc sequences on submicroscopic circular extrachromosomal DNA (episomes). With increased passages in culture (passages 63 72) the cells lose the episome c-myc sequences with a shift of those sequences to double minutes. With additional passage in culture, the c-myc shifts from the double minutes to a chromosomal site der(5)t(5;17)(q11.2;q?11.2). Concomitant with the shift of the c-myc sequences into the chromosomal compartment is a phenotypic change of a shortened cell-doubling time. These studies provide the first molecular evidence of a progression from a submicroscopic location for amplified oncogene sequences to a chromosomal location for the amplified sequences. This molecularly documented model can now be used to test various strategies to prevent incorporation of extrachromosomally located oncogene sequences into chromosomal sites. Prevention of integration of the oncogene sequences into chromosomal sites could modulate progression of patients' tumors. PMID- 2189895 TI - Bacterial phospholipid hydrolysis enhances the destruction of Escherichia coli ingested by rabbit neutrophils. Role of cellular and extracellular phospholipases. AB - Escherichia coli ingested by PMN are promptly growth arrested but undergo limited destruction. We have studied bacterial phospholipid hydrolysis as a possible limiting factor in the disassembly of ingested E. coli, comparing the fates, during phagocytosis by rabbit peritoneal exudate PMN, of three isogenic strains, differing in their content of the pldA gene encoding the principal E. coli phospholipase A (PLA), i.e., pldA-, pldA+, pldA (the latter strain bearing the pldA gene in a multicopy plasmid resulting in a 20-fold increase in PLA content). Ingestion and growth inhibition (greater than 99% within 15 min) were the same for the three strains, but phospholipid degradation differed according to bacterial PLA content: pldA up to 60%, pldA+ up to 30%, and pldA- up to 20%. Since the pldA- strain has no activatable PLA, phospholipid degradation in this strain demonstrates the action of a PMN PLA. Added PLA2-rich ascitic fluid (AF) or purified AF PLA2 increased the rate and extent of degradation of the pldA- strain, provided the enzyme was added before ingestion was complete. 125I-AF-PLA2 binds to both E. coli and PMN and thus can enter the vacuole during phagocytosis. Although up to 50-fold more AF-PLA2 than the PLA2 content of the PMN could be loaded into the PMN in this way, degradation of pldA- E. coli did not exceed 30%. Increased phospholipid degradation had no effect on the degradation of bacterial macromolecules. In contrast, bacterial disassembly manifest as structural disorganization, release of bacterial protein derived material, and inhibition of protein synthesis were markedly enhanced when greater than 50% of prelabelled bacterial phospholipids were degraded. These findings reveal a link between envelope phospholipid degradation and overall bacterial destruction, suggesting therefore that factors limiting PLA action limit the destruction of E. coli ingested by PMN. PMID- 2189897 TI - Improved metabolic control, clinical periodontal status and subgingival microbiology in insulin-dependent diabetes mellitus. A prospective study. AB - The effect of improved metabolic control on the clinical periodontal condition and the subgingival microflora of diseased and healthy periodontal pockets in 6 ambulatory insulin-dependent diabetes mellitus (IDDM) patients was prospectively studied. Duplicate measurements with a time-interval of 3 days were made every 4 moths for assessment of the metabolic status, the clinical periodontal condition and the subgingival microflora. During the study, patients maintained personal oral hygiene measures as they usually did before the study. Neither supplementary dental prophylaxis nor oral hygiene measures were applied during the investigation. Long-term metabolic control (HbAlc) improved significantly with intensive conventional insulin treatment. Gingival redness decreased significantly whereas gingival swelling showed a not significant trend to decrease. It is suggested that microvascular changes associated with improved metabolic control in diabetes mellitus may mediate the observed change in gingival redness. No effect could be demonstrated for probing pocket depth, probing attachment level, bleeding on probing and the plaque index. Statistical analysis of the effect of improved metabolic control on the subgingival microflora revealed that only the % of streptococci increased significantly in diseased periodontal pockets. In general, no significant changes were found in either healthy or diseased pockets with regard to the bacterial flora associated with periodontal disease. The results of the present study indicate that improved metabolic control in IDDM patients may have no potential impetus for an improved clinical periodontal condition nor on the subgingival bacterial flora. It is concluded that the periodontal condition in IDDM patients may only ameliorate when local oral hygiene measures are applied. PMID- 2189896 TI - Reversal of beta-cell suppression in vitro in pancreatic islets isolated from nonobese diabetic mice during the phase preceding insulin-dependent diabetes mellitus. AB - Insulin-dependent diabetes mellitus (IDDM) is characterized by a progressive autoimmune destruction of the pancreatic beta-cells. One of the best-suited animal models for IDDM is the nonobese diabetic (NOD) mouse. In this investigation pancreatic islets were isolated from female NOD mice aged 5-7, 8 11, and 12-13 wk and examined immediately (day 0) or after 7 d of culture (day 7). The mice showed a progressive disturbance in glucose tolerance with age, and a correspondingly increased frequency of pancreatic insulitis. Islets isolated from the oldest mice often contained inflammatory cells on day 0, which resulted in an elevated islet DNA content. During culture these islets became depleted of infiltrating cells and the DNA content of the islets decreased on day 7. Islets of the eldest mice failed to respond with insulin secretion to high glucose, whereas a response was observed in the other groups. After culture all groups of islets showed a markedly improved insulin secretion. Islets from the 12-13-wk-old mice displayed a lower glucose oxidation rate at 16.7 mM glucose on day 0 compared with day 7. Islet (pro)insulin and total protein biosynthesis was essentially unaffected. In conclusion, islets obtained from 12-13-wk-old NOD mice exhibit an impaired glucose metabolism, which may explain the suppressed insulin secretion observed immediately after isolation. This inhibition of beta-cell function can be reversed in vitro. Thus, there may be a stage during development of IDDM when beta-cell destruction can be counteracted and beta-cell function restored, provided the immune aggression is arrested. PMID- 2189898 TI - Evaluation of clinical and radiographic scoring methods before and after initial periodontal therapy. AB - The purpose of the present study was to compare the determination of the attachment level by probing and by measuring bone heights prior to and after the completion of a hygienic phase of periodontal therapy. 68 patients with moderate to severely advanced periodontitis underwent initial (hygiene phase) therapy including scaling and root planing, oral hygiene instructions and the elimination of plaque retention factors. Measurements of pocket probing depths, probing attachment levels and the location of gingival margins in relation to the cemento enamel junction were performed at 4 aspects of each tooth with a thin calibrated probe at a baseline examination and 3 to 5 months following treatment. During these 3 to 5 months, the patients were kept in a maintenance care program. On the full-mouth radiographs obtained at baseline, the distance from the cement-to enamel junction to the marginal alveolar crest was measured in millimeters and as a % of the root length. Furthermore, a subgroup of 11 patients, who were scheduled for modified Widman flap procedures, received another full-mouth radiographic examination before the surgical treatment. In addition, the level of the alveolar crest was assessed with a periodontal probe during the surgical procedure. The comparison of the different clinical and radiographic parameters showed the best correlations between the various radiographic measurements of bone heights (r = 0.87; r = 0.86). Clinical measurements of probing attachment level and probing level of the alveolar crest revealed slightly weaker correlations (r = 0.72). When comparing radiographic bone heights with clinical measurements of probing attachment levels, the lowest correlations were found (r = 0.65; r = 0.61; r = 0.61). PMID- 2189899 TI - Transcranial Doppler studies of flow velocity in middle cerebral artery in weightlessness. AB - Physiological adaptation to weightlessness requires changes in cardiovascular system parameters to maintain homeostasis in the presence of cephalic fluid shifts. The cerebral circulation must respond immediately to these systemic changes or impairment of cerebral function will occur. Blood flow velocities of the middle cerebral artery were measured by transcranial Doppler (TCD) ultrasound in NASA's KC-135 aircraft from four healthy subjects in the supine position. Transcranial Doppler data with accompanying acceleration information were analyzed in three segments in each parabola. Cardiac cycles for each segment of all 20 parabolas were pooled for individual subjects. A Student's t test on the data revealed statistically significant differences in the mean and peak frequencies, systolic/diastolic ratios and Doppler power between positive 2 gz and microgravity (10(-2) gz) as well as between positive 2 gz and negative 2 gz. Velocity waveform profiles differed for the first one third of each segment, with a more resistive waveform developing during the last two thirds. Changes in systemic arterial resistance and/or raised intracranial pressure may contribute to these TCD waveform changes. PMID- 2189900 TI - Third generation cephalosporins: safety profiles after 10 years of clinical use. AB - Compared with aminoglycosides, chloramphenicol, sulfonamides, tetracyclines, and even penicillins, the cephalosporins represent a remarkably safe class of antibiotics. Among the cephalosporins, the extended spectrum, third generation agents developed generally produce few side effects and appear to be less allergenic than the penicillins. Nephrotoxicity has not been a problem at recommended doses. Some third generation agents can cause hypoprothrombinemia if not administered with vitamin K, and disulfiram-like reactions occur with some agents because of the presence of a thiomethyl tetruzole moiety affixed to the cephem nucleus. There is a greater incidence of diarrhea associated with the agents excreted through a primarily biliary route, and this may contribute to the selection of drug resistant bacteria. Some agents are less active against staphylococci and their use may result in an increased incidence of superinfection or overgrowth of enterococci. If attention is given to the potential for adverse effects, many of these problems can be avoided and the third generation cephalosporins can be used safely in hospitals, nursing homes, and home care settings. PMID- 2189901 TI - Lack of effect of the vasodilator pinacidil on insulin secretion in healthy humans. AB - Pinacidil is a new antihypertensive vasodilator drug which is supposed to act by opening of ATP-sensitive and glibenclamide-sensitive K+ channels in vascular smooth muscle cell membranes. Similar K+ channels play an important role in insulin secretion from pancreatic islets cells. Inhibition of insulin secretion has been demonstrated with high concentrations of pinacidil in vitro. In the present study the insulin response to oral glucose were studied in six healthy subjects before and on the last day of 2 weeks treatment with pinacidil. The drug was given by the oral route 12.5 mg bid in the first week and 25 mg bid in the second. There were no significant changes in fasting blood levels of insulin or glucose, glucose-stimulated insulin secretion, or oral glucose tolerance during pinacidil administration. These results may suggest that pinacidil at therapeutic concentrations does not activate insulin regulating K+ channels in pancreatic islet cells. PMID- 2189902 TI - Penbutolol and carteolol: two new beta-adrenergic blockers with partial agonism. AB - Penbutolol and carteolol are two new long acting, nonselective beta-adrenergic blockers which have been approved for the treatment of systemic hypertension. Both drugs have intrinsic sympathomimetic activity (partial agonist activity), however, less than that seen with pindolol. They appear to cause less resting bradycardia than propranolol, have no effect on lipids and lipoproteins, and have favorable side effect profiles. PMID- 2189903 TI - Evaluation of the clinical pharmacology of nilvadipine in patients with mild to moderate essential hypertension. AB - Eighty-four patients with diastolic blood pressure ranging from 100-115 mm Hg were randomized into a multicenter, parallel, double-blind, placebo-controlled, dose response study with nilvadipine (6 mg, 8 mg, 10 mg tid for 28 days). The hypotensive response pattern to nilvadipine was similar with all three doses although duration of response was dose dependent. Maximal decreases in diastolic blood pressure occurred at 1 hour when assessed on days 1 and 15 (16.0, 17.4, and 15.8 mm Hg, vs 17.2, 18.7, and 17.5 mm Hg, respectively). The hypotensive effect remained significant compared to placebo for at least 4 hours after dosing. The increase in heart rate associated with the maximal hypotensive response was minimal and not clinically significant (day 1: 7.6, 5.2, and 4.0 beats/min with 6, 8, and 10 mg; day 15: 4.0, 5.1, 2.6 beats/min with 6, 8, 9, and 10 mg, respectively). Finally, a correlation between plasma drug concentrations and nilvadipine-induced hypotensive response was observed (r = 0.48). Black and white hypertensive patients had similar hypotensive responses. Plasma nilvadipine concentrations on day 15 were similar to those on day 1 suggesting no accumulation of drug with a tid regimen. The most common drug related side effect was headache; less frequently seen were dizziness, edema, palpitations, and abdominal pain. Nilvadipine was well tolerated (only three patients were discontinued due to side effects). The efficacy, lack of tachycardia, and side effect profile observed in this study suggest that nilvadipine may be an important addition to the treatment of hypertension. PMID- 2189904 TI - Acute interstitial nephritis with glomerulopathy due to nonsteroidal anti inflammatory agents: a review of its clinical spectrum and effects of steroid therapy. AB - We reviewed case reports of patients who developed acute renal failure and/or nephrotic range proteinuria in the course of receiving treatment with nonsteroidal anti-inflammatory agents (NSAIA). Those cases that contained information sufficient to confirm the diagnosis of acute interstitial nephritis with glomerulopathy (AING), including a suggestive clinical syndrome with appropriate renal biopsy findings, were further analyzed to achieve a more complete description of this clinical entity and its responsiveness to steroid treatment. Analysis of the cases that fulfilled the inclusion criteria confirmed that the disorder is twice as common in women and occurs mainly in elderly people, usually after long-term use of NSAIAs for musculoskeletal problems. Fenoprofen was implicated in 47% of the cases. Evidence of systemic hypersensitivity was uncommon. Two thirds of the cases displayed clinical and/or histological evidence of both acute interstitial nephritis and increased glomerular permeability. These findings strongly suggest that this condition is distinct from other drug-induced "allergic" acute interstitial nephritides. In the absence of complicating factors, all patients improved following discontinuation of the offending agents. No evidence was found to suggest that steroid therapy altered the clinical course of this process. PMID- 2189905 TI - Trichothiodystrophy: review of sulfur-deficient brittle hair syndromes and association with the ectodermal dysplasias. AB - Trichothiodystrophy appears to represent a central pathologic feature of a specific hair dysplasia associated with several disorders in organs derived from ectoderm and neuroectoderm. The key finding is brittle hair with low sulfur content, but alternating dark and light bands under polarizing microscopy, trichoschisis, and absent or defective cuticle are additional important clues for the diagnosis of trichothiodystrophy. Our review of the literature revealed extensive associated findings in trichothiodystrophy. Classification of patients with trichothiodystrophy and other dysplasias is difficult because diminution of sulfur-rich protein in hair is not a sufficient marker to allow precise differentiation, although several similar ectodermal dysplasias can be excluded by demonstration of abnormal sulfur content in hair of patients with trichothiodystrophy. Patients with trichothiodystrophy should have a thorough evaluation for other associated manifestations, including investigation of photosensitivity and DNA repair defects. Detection of low-sulfur brittle hair syndrome is also important for genetic counseling because the disease appears to be inherited in an autosomal recessive pattern. PMID- 2189906 TI - A double-blind vehicle-controlled study of R 68 151 in psoriasis: a topical 5 lipoxygenase inhibitor. AB - Recently the pharmacologic role of leukotrienes (LTs), especially that of LTB4, has been intensively investigated in psoriasis. In vitro, R 68 151 is a potent 5 lipoxygenase inhibitor and consequently reduces LTB4 formation. Therefore the role of an in vitro 5-lipoxygenase inhibitor and its clinical use in psoriasis were evaluated with topical R 68 151 in a double-blind vehicle-controlled study. Eighty-eight patients with localized psoriatic lesions were treated twice daily with R 68 151 2% ointment (n = 44) or vehicle ointment (n = 44) during 4 weeks. Most patients (n = 73) had psoriasis vulgaris (n = 37, R 68 151; n = 36, vehicle). In 27% of the R 68 151-treated patients with psoriasis vulgaris, the lesions disappeared or showed marked improvement, compared with 8% in the vehicle group (X2, p = 0.06). The scores in global evaluation, however, were significantly different between both treatment groups (p less than 0.05, Mann Whitney U test). The improvement of the mean symptom score with R 68 151 was 46% for scaling and 34% for erythema at the end of the study compared with an improvement of 6% and a deterioration of 3%, respectively, in the control group (p less than 0.05, p less than 0.01; Mann-Whitney U test). The global evaluation in the total group of patients with psoriasis (all different subtypes) was consistent with the response rate in the group of patients with psoriasis vulgaris: 30% in the test group versus 11% in the control group (X2, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2189907 TI - Cutaneous nickel sensitivity in Toronto, Canada. AB - Patch tests were administered to 1074 subjects with suspected contact dermatitis by the method recommended by the International Contact Dermatitis Research Group. Of 629 subjects tested with 5% nickel sulfate in petrolatum, 10.5% had positive reactions (males, 5.1%; females, 16.7%). Of 447 subjects tested with 2.5% nickel sulfate in petrolatum, 11.9% reacted (males, 7.7%; females, 16.9%). In 447 subjects in whom the relationship between clinical findings and the patch test response was evaluated (i.e., relevance), more than 90% of the responses could be related to a past or present problem with contact dermatitis. The sites of involvement were not different between nickel-sensitive subjects and the overall population tested, except in the case of foot involvement, which was underrepresented in the nickel-sensitive group. Patients who had positive responses to nickel reacted more frequently to marginal irritants such as formaldehyde and benzoyl peroxide. This finding may suggest a reduction in the irritancy threshold in nickel-sensitive subjects. In most instances, domestic rather than occupational exposure was thought to account for the induction of nickel allergy. PMID- 2189908 TI - Localized childhood vulvar pemphigoid. AB - Bullous pemphigoid is a disease primarily of the elderly and is uncommon in children. A distinct localized variant of this condition appears to occur in children and is limited to the vulva. Two children with localized disease are discussed. PMID- 2189910 TI - Oedemerid blister beetle dermatosis: a review. AB - Blister beetle dermatosis is a distinctive vesiculobullous eruption that occurs after contact with three major groups of beetles (Order: Coleoptera). It is caused by a vesicant chemical contained in the body fluids of the beetles. The smallest and least known family is the Oedemeridae. Although there are few references in the medical literature, blister beetle dermatosis caused by oedemerids may be more common and widespread than currently recognized. The best known family is the Meloidae with numerous species worldwide causing blistering. The vesicant chemical in both Oedemeridae and Meloidae is cantharidin. The third group of blister beetles includes species of the genus Paederus (Family: Staphylinidae). The clinicopathologic picture differs because this genus contains a different vesicant agent, pederin. The clinicopathologic features of oedemerid blister beetle dermatosis are described. The world medical and relevant entomologic literature is reviewed. PMID- 2189909 TI - The use of chlorambucil in the treatment of bullous pemphigoid. AB - Twenty-six patients with bullous pemphigoid were treated with a combination of chlorambucil and a systemic corticosteroid; 23 completed treatment. The corticosteroid requirement during therapy was reduced by 50% compared with that reported for corticosteroid and azathioprine, and the mean total duration of therapy was only 5 months. The side effects of chlorambucil have not been significant, but in 30% of the patients a mild transient thrombocytopenia developed. In one patient a more significant marrow suppression developed. Despite complete recovery, chlorambucil treatment was discontinued in this patient. There was no evidence that either the disease treated in this way or the treatment itself had an adverse effect on survival during therapy or for the mean follow-up period of 36 months. Patients who responded less well to treatment tended to be younger, and their disease was more severe in that a higher dosage was required for initial control. Patients in whom thrombocytopenia developed were older and had lower pretreatment platelet levels. PMID- 2189911 TI - Linear IgA bullous dermatosis after heart transplantation. PMID- 2189912 TI - Bullous pemphigoid and multiple sclerosis. PMID- 2189913 TI - Beta-lactamases, beta-lactamase inhibitors, and skin and skin-structure infections. AB - beta-Lactamases have been known since the early 1940s when they were recognized as a major mechanism of resistance in Staphylococcus aureus. The synthesis of semisynthetic penicillins provided agents that overcame the resistance of staphylococci, but as gram-negative bacteria became increasingly important as the cause of infections, plasmid-mediated beta-lactamases were recognized in the Enterobacteriaceae, Haemophilus, and chromosomally mediated beta-lactamases in Klebsiella, and Bacteroides were found to be the mechanism of resistance of these species to ampicillin and related penicillins. Two approaches to the problem have been developed. One is to make stable compounds. This has been possible in the cephalosporin family. The other method has been to find inhibitors of beta lactamases. Clavulanate is a beta-lactamase inhibitor that, in combination with amoxicillin, allows the combination to inhibit many of the organisms that are resistant to amoxicillin. Similarly, clavulanate has been combined with ticarcillin to provide a parenteral agent to inhibit beta-lactamase-producing bacteria and retain activity against Pseudomonas. Sulbactam has been combined with ampicillin. The combination of suicide inhibitors with other beta-lactams has provided agents that inhibit many of the bacteria present in mixed cutaneous infections. Clinical studies have established the efficacy of the clavulanate amoxicillin and clavulanate-ticarcillin combinations in skin and skin-structure infections. These agents offer an alternative to other drugs when treating cutaneous infections. PMID- 2189915 TI - Use of non-sterile gloves in clinical practice. AB - This paper reviews the use of non-sterile gloves in dental practice. It is now considered to be normal practice to wear gloves for all dental procedures and although there is considerable controversy regarding patterns of glove use, there is increasing evidence to the effect that single patient use is indicated. Careful use of gloves and proper hand care are key components to effective cross infection control in clinical practice. PMID- 2189914 TI - Histological, microbiological and haematological investigations in denture induced stomatitis. AB - Biopsy specimens of palatal mucosa from 10 edentulous female subjects exhibiting the signs of chronic atrophic denture-induced stomatitis were fixed and processed to produce sections which were quantitatively analysed by light microscopy. The type and degree of surface keratinization, the epithelial thickness and basement membrane morphology were assessed. Microbiological and haematological evaluations were related to the histological findings. It was found that within this clinical entity of palatal inflammation there was considerable variation in tissue response at a cellular level, and that the numbers of organisms associated with the inflammatory reaction appeared to be fewer in patients with abnormal haematological status. PMID- 2189916 TI - Urinary incontinence. PMID- 2189917 TI - Voiding dysfunction in patients with multiple sclerosis. PMID- 2189918 TI - [The quantitative characteristics of the metabolism of antitumor compounds]. AB - Methodical approaches to quantitative study of biotransformation of antitumor drugs have been described and classified. Most widely used types of models have been described. Proposed algorithm of interpretation of obtained experimental data may be used for selection of suitable model description of a compound and characterization of its pharmacokinetic properties. PMID- 2189919 TI - [A cytomorphological analysis of the adhesion of fungi of the genus Candida to human and animal epithelial cells]. AB - Morphological pattern of adherence of Candida genus fungi to human and animal epithelial cells have been studied using histological and cytological methods. The interspecific differences of epithelial adhesive properties were observed: in one case, the mucous membrane epitheliocytes of different localization had different adhesive properties. Adhesive properties vary significantly within one type of epithelial cells. In individual epitheliocyte, the adherence of fungal blastospores was nonuniform: the greater density was observed in peripheral areas of cytoplasm. PMID- 2189920 TI - [The selective reduction of nitro compounds by E. coli cells]. AB - Nitroreduction of 2,4-dinitro-5H-11-p-R-phenyl-[b,f]-1,4-diazepines and 4-(2'-R 3',5'-dinitro)benzoyl-3,4-dihydroquinoxalinones-2 by E. coli with formation of 2 nitro-4-amino-11-p-R-phenyldibenzo-[b,f]-1,4-diazepines and 4-(2'-R-3'-nitro-5' amino)-benzoyl-3,4-dihydroquinoxalinones-2 has been demonstrated using a set of physical and chemical methods. PMID- 2189921 TI - A three-dimensional model of tongue movement based on ultrasound and x-ray microbeam data. AB - Point-tracking techniques provide timing information about structural movements of the tongue. Imaging techniques provide information about cross-sectional and pharyngeal tongue shape and movement. This study joined these techniques in a single subject. Five pellets on the tongue surface were tracked using x-ray microbeam, and the midsagittal and coronal planes of the tongue were imaged using real-time ultrasound. The speech materials were the consonants [s] and [l] and the vowels [i], [a], and [o] combined in VCVCe utterances. Analyses concentrated on the difference in tongue movements related to the two consonants. A model of tongue movement was developed, in which critical features of consonant shape and position dominated the tongue opening movement. In this model, the tongue is divided into subdivisions termed "functional segments" in both the sagittal and coronal planes. Movements of the functional segments created observable opening movement patterns. PMID- 2189922 TI - A multiple-frequency hydrophone calibration technique. AB - A method is described for comparing the sensitivity of two hydrophones over the frequency range 1-15 MHz. This technique forms the basis for the dissemination of national ultrasonic standards in the U.K. over this frequency range. A reference hydrophone is placed in an ultrasonic field and then the device being calibrated is substituted and the two output voltages are compared. This substitution method utilizes a broadband ultrasonic field produced by nonlinear propagation. Thus it is possible to cover the whole frequency range with a single measurement on each hydrophone. The overall uncertainty in the intercomparison of two hydrophones increases from +/- 4.2% at 1 MHz to +/- 8.2% at 15 MHz (95% confidence level). The method has been compared with discrete-frequency substitution, time-delay spectrometry, and absolute calibrations using the National Physical Laboratory (NPL) Primary Standard Laser Interferometer. Various designs and sizes of hydrophones were compared, and agreement was within the combined random uncertainties for all the comparisons. PMID- 2189923 TI - Differences in children's peer sociometric and attribution ratings due to context and type of aggressive behavior. AB - Sociometric and attribution (internality and responsibility) ratings of boys performing different kinds of aggression (hostile and instrumental hitting and pushing) and of neutral behavior occurring in two contexts (provoked and unprovoked) were investigated in an analogue fashion. Thirty fifth- and sixth grade boys viewed and rated 12 brief videotaped scenes of two unfamiliar male peers interacting, presented in one of six random orders. Provoked aggression resulted in less dislike, less worthiness of punishment, and greater attribution to external causes than unprovoked aggression. Instrumental and hostile aggression produced lower liking ratings and were viewed as more deserving of punishment than neutral behavior but did not differ from each other. Results support distinctions between provoked and unprovoked aggression but not between hostile and instrumental aggression, at least in terms of their functional impact on peer judgements. PMID- 2189924 TI - Ocular anomalies in fragile X syndrome. AB - Fragile X (fra[X]) syndrome is a newly discovered, but relatively common, genetic disorder with an estimated frequency of 1:1000. Several ocular dysfunctions may be associated with this syndrome, but there are few articles that fully report on these. A review of this genetic disorder is provided, as well as a discussion of a case review of a family with three siblings with fragile X syndrome. Since this disorder is the most common familial cause of mental retardation, is second only to Down's syndrome as a genetic cause for mental retardation, and may play a significant role in learning disabilities, the eye care practitioner should be aware of its importance. PMID- 2189925 TI - Unconscious fantasy: a reconsideration of the concept. AB - Despite general agreement about the clinical importance of unconscious fantasy, the concept itself has remained unclear. After reviewing Freud's work on the subject, the conceptual dilemma is specified: where in current psychoanalytic theory do we place this important, dynamically repressed, structuralized mental content? Three conceptual paths have been followed in attempting to deal with this problem. The first emphasizes the structural, tripartite model, discarding topographic concepts. The second replaces the structural model with a schema model borrowed from academic psychology. The third combines the structural and topographic models. None of these approaches is entirely satisfactory and without problems. Because of their central role in mental life, unconscious fantasies deserve careful definition. They should be distinguished from conscious fantasies and daydreams as well as from the process of fantasizing. They are differentiated from other varieties of unconscious content by their enduring quality and their organized, storylike quality reflecting the distortions typical of the primary process. As dynamically unconscious templates from the childhood past, they shape subsequent compromise formations and are relatively impervious to new experience. The development of psychoanalytic theory from a macrostructural to a microstructural emphasis is discussed in relation to the unconscious fantasy concept. PMID- 2189926 TI - Our analytic heritage: ideals and idealizations. AB - The relation between ideals and idealizations is examined with regard to the aims of the American Psychoanalytic Association in advancing psychoanalytic education, practice, and research. Ideals are essential for preserving the past and as guides for the future. However, the idealizations that often develop in response to new discoveries and innovations may lead to a defensive clinging to the past as well as to an overly enthusiastic embrace of new ideas. Both these forms of idealization may serve as powerful resistances to creative and constructive change. PMID- 2189927 TI - Access to quality medical care. PMID- 2189928 TI - Dupuytren's disease. PMID- 2189929 TI - Randomized crossover comparison of high-dose intravenous metoclopramide versus a five-drug antiemetic regimen. AB - In a randomized open crossover study, the antiemetic efficacy of a five-drug antiemetic regimen consisting of metoclopramide, dexamethasone, diazepam, diphenhydramine, and thiethylperazine was compared to that of high-dose metoclopramide. Thirteen patients treated with cisplatin combination chemotherapy regimens were evaluated. The study was terminated prior to accrual of the planned number of patients because of the statistically significant difference in efficacy between treatments found at interim analysis. The duration of nausea and number of vomiting episodes on the day of chemotherapy were significantly less (p less than 0.01) after receiving the five-drug combination. After receiving the five-drug regimen, 77% of the patients did not experience any episodes of vomiting on day 1, and 8% of patients had only one episode. In contrast, only 31% of patients treated with high-dose metoclopramide did not have any episodes of vomiting on day 1, and 61% of the patients had five or more episodes. None of the patients treated with the five-drug regimen required additional antiemetic administration. Although both regimens were, in general, well tolerated, when given the choice of continuing antiemetic therapies, 92% of the patients preferred the five-drug antiemetic combination. PMID- 2189930 TI - Review of the rectal use of opioids. AB - The rectal route for the administration of opioid analgesics is often forgotten by physicians seeking alternatives to the oral route. This article reviews the physiology of rectal drug absorption and such data as exists on the different opioids that have been administered by this route. Conventional fatty-based suppositories have a place in the management of chronic pain but the variability in dissolution and drug absorption limit their usefulness. Recently, sustained release vehicles have become available that offer the prospect of the attainment of steady analgesic drug concentrations with once or twice daily dosing. Early studies with the morphine hydrogel suppository suggest that it may be capable of fulfilling this prospect. Their inherent safety, as dose-dumping is impossible, will make them suitable for use in the home. PMID- 2189931 TI - [A surgical case of atrial septal aneurysm associated with rheumatic mitral and tricuspid disease and coronary-pulmonary artery fistula]. AB - A case of atrial septal aneurysm associated with combined valvular disease and coronary-pulmonary fistula (C-PA fistula) was presented. The patient successfully underwent mitral valve replacement, excision and closure of the aneurysm, tricuspid annuloplasty and closure of C-PA fistula. Atrial septal aneurysm is a rare anomaly and its natural course is thought to be generally good without significant clinical symptoms. However, complications such as cerebral and pulmonary embolism, or occlusion of the atrioventricular vales by the prolapsed aneurysm were reported to occur in small number of cases. In this case, diagnosis of the aneurysm was made by 2-D and Doppler echocardiography and further confirmed by cineangiography. Routine echocardiographic examinations will serve as useful noninvasive method for detection and follow up study of this anomaly. PMID- 2189932 TI - [Successful repair of a cardiac lipoma of the left ventricular free wall--a case report]. AB - We recently encountered a patient with a very rare type of cardiac lipoma, which occurred at the left ventricular free wall and grew into the left ventricular cavity. No surgical treatment of this type of cardiac lipoma has been reported in literature. The patient was a 63-year-old woman who visited our hospital with a chief complaint of palpitation. At the outpatient clinic of our hospital, a tumor of the left ventricle was disclosed by echocardiography. After hospitalization, the patient was diagnosed as cardiac lipoma by CT scans and MR images. She was operated as follows. The apex of the left ventricle was incised and the cardiac cavity was exposed. The lipoma had its root approximately in the center of the posterior free wall of the left ventricle and had grown into the left ventricular cavity with a size of 2.5 X 2.5 X 1.8 cm and a weight of 2.8 g. After removal, the postoperative course was uneventful, but the chief complaint (palpitation) still persisted. Postoperative Holter electrocardiography disclosed that the patient had suffered from sick sinus syndrome and that palpitation had not originated from the cardiac lipoma. PMID- 2189933 TI - [A successful case of mediastinal cystic lymphangioma and statistical considerations in the Japanese literature]. AB - A 38-year-old man with large mediastinal cystic lymphangioma was successfully treated. Although he was asymptomatic, mass lesion on chest X-ray, pointed out two years ago, has rapidly increased in its size. The operation was performed through right thoracotomy and the cyst was unilobular and 10 X 8 X 8 cm in size, presented in the right upper anterior mediastinum. It contained about 250 ml of yellowish clear fluid with very thin wall, which was verified as tissue lymph by biochemical examination. Only 27 cases of mediastinal cystic lymphangiomas have been reported in the Japanese literature by 1988. Complete resection of the cyst should be recommended, since almost no evidence of postoperative recurrence would be expected. PMID- 2189934 TI - Ancestral polymorphisms of MHC class II genes: divergent allele advantage. PMID- 2189935 TI - Evolution of the MHC: lessons from the nonmammalian vertebrates. PMID- 2189936 TI - The structural basis of alloreactivity. PMID- 2189937 TI - Control of transcription at the murine A alpha locus. PMID- 2189939 TI - Primary prevention trials in cardiovascular disease. PMID- 2189938 TI - Genetics of HLA class II regulation. PMID- 2189940 TI - Trypsin-like hatching protease from mouse embryos: evidence for the presence in culture medium and its enzymatic properties. AB - Enzymatic properties of a protease involved in hatching of mouse embryos were examined. A trypsin-like protease, which most efficiently hydrolyzed t butoxycarbonyl-Leu-Ser-Thr-Arg-4-methylcoumaryl-7-amide, was demonstrated in culture medium of mouse hatching embryos. The enzyme was strongly inhibited by diisopropyl fluorophosphate, phenylmethanesulfonyl fluoride, leupeptin, antipain, N alpha-tosyl-L-lysyl-chloromethane, soybean trypsin inhibitor, and Trasylol, but not or weakly inhibited by p-chloromercuribenzoic acid, EDTA, E-64, pepstatin, chymostatin, and bestatin, suggesting a trypsin-like serine proteinase. The protease activity in the medium gradually elevated during the course of hatching, whereas the embryo-associated activity showed no significant change. Furthermore, pyroglutamyl-Leu-argininal, the strongest inhibitor for the enzyme among peptidyl argininals, all of which are potent trypsin inhibitors, showed the strongest inhibition toward hatching. Thus, a trypsin-like protease secreted from hatching embryos into the culture medium may participate in mouse hatching, probably as a hatching enzyme. PMID- 2189941 TI - Study of the differentiation of secretory cells in the golden hamster oviductal epithelium by use of a monoclonal antibody. AB - The ontogeny of an oviductal zona pellucida glycoprotein, designated ZP-0, in the golden hamster oviductal epithelium was investigated by means of light and electron microscopic immunolabeling studies using a monoclonal antibody. Light microscopic immunohistochemistry showed that ZP-0 appeared in the oviductal epithelium from 9.5 to 10.5 days after birth. At first, ZP-0 appeared in the Golgi region of the epithelial cells, and then increased in amount as development progressed to fill the supranuclear cytoplasm. Electron microscopic observations showed that rough endoplasmic reticulum and Golgi apparatus were well developed in non-ciliated cells of the ampullar and isthmic segments at 10.5 days after birth. Secretory granules appeared near the Golgi apparatus and markedly increased in number until 15.5 days after birth. Ultrastructural immunocytochemistry showed that ZP-0 appeared in the well-developed Golgi apparatus and then was stored within the secretory granules of developing secretory cells. ZP-0 was never present in the ciliated cells. These results indicate a coincidence between the beginning of ZP-0 biosynthesis and the morphological cytodifferentiation of secretory cells in the golden hamster oviduct during postnatal development. This leads us to the conclusion that ZP-0 is a possible differentiation marker of the golden hamster oviductal secretory cell. PMID- 2189942 TI - Fully differentiated Xenopus eye fragments regenerate to form pattern-duplicated visuo-tectal projections. AB - In order to determine if differentiated Xenopus retina is capable of undergoing regeneration and duplicative pattern formation, we devised a new surgical technique for removal of the temporal two-thirds of the retina. In a series of progressively older larval eyes starting with late tailbud stage embryos (stage 38) and extending to limb-bud stage tadpoles (stage 48), nasal one-third-sized eye fragments successfully regenerated to form nearly normal sized eyes over 75% of the time. Histological preparations showed that early wound healing involved the formation of a neuroepithelium at the ventro-temporal region of the fragment. The pigmented retinal epithelium and associated retinal tissue appeared to be involved in this process. Animals from each stage were reared through metamorphosis and electrophysiologic techniques were employed to determine visuo tectal projections. Seventy percent of stage 38 animals showed evidence of pattern-duplicated projections. Ninety percent of their responding tectal points showed duplicate innervation from two retinal regions. Older animals (stages 44 to 48) showed less duplication. Only 52% of their responding tectal points duplicated (P less than 0.001). Thus, fully differentiated Xenopus retina can undergo regeneration and duplicative pattern formation similar to that shown by embryonic retinal tissue. PMID- 2189943 TI - Discussion of "ABH antigen typing in bone tissue". PMID- 2189944 TI - Some effects of mechanical trauma on the development of primary cancers and their metastases. AB - Posttraumatic inflammation and, much less commonly, mechanical trauma itself may affect the clinical course of cancer. There is no evidence that a single incident of trauma can cause cancer, although posttraumatic chronic inflammation may be associated with carcinogenesis. In patients with cancer at the time of trauma, inflammation and repair processes may inhibit or enhance cancer growth, and trauma and its sequelae may increase the rates of invasion and dissemination. PMID- 2189945 TI - Release of tissue paraquat into formalin solution during fixation. AB - Formalin-fixed tissues and formalin solutions are among the most frequently found materials in pathology and forensic science laboratories. However, these materials are seldom used for the identification of poisons for forensic toxicology purposes. In this study, the possibility that paraquat may be released from formalin-fixed tissues during the fixation process was investigated. However, because of the interference of formaldehyde on the reduction of paraquat with dithionite reagent, paraquat in formalin solutions was treated with ion-pair column chromatography and then determined by measuring the derivative spectrum of reduced paraquat. The results show that the interference of formalin on paraquat determination has been eliminated by the proposed method. Furthermore, a study on the formalin solutions of fixed organs in cases with suspected paraquat intoxication revealed that portions of tissue paraquat had been released into formalin during the fixation process. Moreover, the paraquat levels in formalin increased with increased storage time. Therefore, these data suggest that the combined concentrations of paraquat in the formalin-fixed tissues and formalin solutions might reflect more reliably the total paraquat in the postmortem tissues. This investigation could be of value to the forensic toxicologist, especially in cases in which no fresh tissue samples are available for analysis. PMID- 2189946 TI - Undiagnosed, untreated acute lymphoblastic leukemia presenting as suspected child abuse. AB - Natural disease being mistaken for child abuse is rare. A two-year-old child was found unresponsive at home and transported to a local hospital, where she expired in the emergency room. Several cutaneous contusions were observed. Prior to the autopsy it was learned that an anonymous report of "child abuse" had been previously filed concerning this child. At autopsy there were multiple metasynchronous cutaneous contusions, but no radiologic or gross evidence of other injuries. A pericardial effusion, massive hepatosplenomegaly and generalized lymphadenopathy were apparent. The bone marrow, liver, spleen, lymph nodes, kidneys, pancreas, heart, stomach, and dura mater showed a monotonous lymphocytic infiltrate. Immunocytochemical studies confirmed the diagnosis of acute lymphoblastic leukemia of childhood. This case reaffirms the need for an objective examination of all cases by a forensic pathologist. PMID- 2189948 TI - High agreement but low kappa: II. Resolving the paradoxes. AB - An omnibus index offers a single summary expression for a fourfold table of binary concordance among two observers. Among the available other omnibus indexes, none offers a satisfactory solution for the paradoxes that occur with p0 and kappa. The problem can be avoided only by using ppos and pneg as two separate indexes of proportionate agreement in the observers' positive and negative decisions. These two indexes, which are analogous to sensitivity and specificity for concordance in a diagnostic marker test, create the paradoxes formed when the chance correction in kappa is calculated as a product of the increment in the two indexes and the increment in marginal totals. If only a single omnibus index is used to compared different performances in observer variability, the paradoxes of kappa are desirable since they appropriately "penalize" inequalities in ppos and pneg. For better understanding of results and for planning improvements in the observers' performance, however, the omnibus value of kappa should always be accompanied by separate individual values of ppos and pneg. PMID- 2189947 TI - Natural products as a source of potential cancer chemotherapeutic and chemopreventive agents. AB - Recent advances in the chemistry of novel bioactive natural products are reported. This research is directed to the exploration of plants with confirmed activity in bioassays designed to detect potential cancer chemotherapeutic and chemopreventive agents. Structural work and chemical studies are reported for several cytotoxic agents from the plants Annona densicoma, Annona reticulata, Claopodium crispifolium, Polytrichum obioense, and Psorospermum febrifugum. Studies are also reported based on development of a mammalian cell culture benzo[a]pyrene metabolism assay for the detection of potential anticarcinogenic agents from natural products. In this study a number of isoflavonoids and flavonoids with antimutagenic activity have been discovered. PMID- 2189949 TI - Diagnostic methods for peripheral arterial disease in the San Luis Valley Diabetes Study. AB - Peripheral arterial disease (PAD) is a frequent complication of diabetes mellitus. In the first phase of the San Luis Valley Diabetes Study, diagnostic criteria for PAD were evaluated in 607 controls and 343 diabetics. Normal ranges, and the lowest 2.5 percentile of the distribution of ankle/arm systolic blood pressure ratios were derived from a non-diabetic subset of the population with a very low probability of PAD. From this subgroup, abnormal ankle/arm ratios were defined as less than: 0.94 at rest, 0.73 after exercise, and 0.78 after reactive hyperemia. Using these criteria, PAD was identified in 130 subjects from the study population of 950 (prevalence of 13.7%). In contrast, a history of intermittent claudication, or an absent pulse in the extremity were uncommon findings in the study population, and thus had a low sensitivity and positive predictive value for PAD diagnosed by vascular laboratory criteria. We conclude that vascular laboratory tests provide a useful, and objective means of determining the prevalence of PAD in a geographically-based population of diabetic and control subjects. PMID- 2189951 TI - Long-term adjuvant tamoxifen in early breast cancer: effect on bone mineral density in postmenopausal women. AB - The decrease in sex steroid hormone levels after the onset of menopause is associated with bone loss and subsequent osteoporosis. Tamoxifen has antiestrogenic properties and may thus theoretically decrease bone mineral density, particularly after long-term treatment. Bone mineral density (BMD) was assessed in 75 recurrence-free postmenopausal breast cancer patients included in a randomized trial of adjuvant tamoxifen (40 mg daily) for 2 or 5 years versus no adjuvant endocrine therapy. The measurements were done about 7 years after the initial randomization. BMD was measured with single-photon absorptiometry (SPA) at two levels of the distal forearm representing cortical and trabecular bone. The BMD was found to be similar among tamoxifen patients compared with the controls. For cortical bone, the BMD was 1.03 g/cm2 (95% confidence interval [Cl], 0.97 to 1.09) among tamoxifen patients and 1.03 g/cm2 (95% Cl, 0.96 to 1.11) in controls. For trabecular bone, the values were 0.74 g/cm2 (95% Cl, 0.70 to 0.79) and 0.73 g/cm2 (95% Cl, 0.68 to 0.79), respectively. The results thus did not indicate an accelerated postmenopausal bone loss with long-term adjuvant tamoxifen. PMID- 2189950 TI - Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16. AB - The National Surgical Adjuvant Breast and Bowel Project (NSABP) conducted a randomized clinical trial to determine whether tamoxifen (TAM) plus chemotherapy is more effective than TAM alone in improving disease-free survival (DFS), distant disease-free survival (DDFS), and survival (S) of positive-node, TAM responsive patients aged greater than or equal to 50 years. Women were randomized among three treatment groups: (1) TAM alone, (2) Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cyclophosphamide, and TAM (ACT), or (3) melphalan (L PAM), fluorouracil (5-FU), and TAM (PFT). The PFT arm was later modified so that new patients also received Adriamycin (PAFT). Findings from 1,124 eligible patients through 3 years of follow-up indicated a significantly better DFS for ACT-treated patients than for those receiving TAM alone (84% v 67%; P = .0004). An advantage in DDFS and S was also observed after ACT therapy (83% v 73% [P = .04 in the former] and 93% v 85% [P = .04 in the latter]). Both the DFS and DDFS of PAFT-treated patients were better than in those treated by TAM alone (83% v 66%, P = .0002 and 85% v 73%, P = .003). PFT patients also fared better in DFS and DDFS than TAM patients (81% v 72%, P = .07 and 85% v 74%, P = .02). Odds ratios consistently favored the three TAM-plus-chemotherapy groups. No significant S advantage is as yet evident in favor of the PAFT or PFT groups. Of importance is the failure of these studies to demonstrate an unfavorable interaction between the drug regimens used and the TAM, which was administered simultaneously. The findings related to the use of PAFT and PFT are of more biologic than clinical significance since L-PAM is rarely used in the treatment of breast cancer. The major conclusion from this study is the observance of a better outcome in positive-node breast cancer patients aged greater than or equal to 50 years from the use of postoperative prolonged TAM and short-course AC therapy (completed in 63 days) than from prolonged TAM therapy alone. PMID- 2189952 TI - Measurement of estrogen and progesterone receptors in human breast tumors: enzyme immunoassay versus binding assay. AB - To determine whether we could replace our current binding assay (BA) method for measurement of estrogen receptors (ERs) and progesterone receptors (PRs) with the recently developed enzyme immunoassay (EIA) method, we compared simultaneous measurements of ERs and PRs in frozen breast tumor samples by both methods. A value of greater than or equal to 10 fmol/mg cytosol protein was defined as positive. There was agreement between the BA and EIA on whether the sample was positive or negative in 75 of 91 (82%) samples measured for ERs and in 74 of 93 (80%) for PRs. When the threshold value for a positive assay was redefined as greater than or equal to 20 fmol/mg protein, there was agreement in 85 of 91 (93%) samples for ERs and 85 of 93 (91%) for PRs. The numerical value for ERs by EIA was not consistently greater or less than ERs by BA, but the difference between the EIA and BA measurement increased as the size of the measurement increased. We did not see an excess of premenopausal patients whose ERs by BA were negative and whose ERs by EIA were positive. Although we performed a linear regression analysis and determined the Pearson correlation coefficient to compare the BA and EIA as reported by others, we show that this analysis may be misleading when the objective is to demonstrate similarities between these methods. Our study shows that the EIA can be confidently used in place of the BA. However, a threshold value for a positive EIA should be confirmed clinically in future studies. PMID- 2189953 TI - Intraperitoneal recombinant alpha-2-interferon alternating with cisplatin as salvage therapy for minimal residual-disease ovarian cancer: a phase II study. AB - A phase II study was initiated in March 1987 at the Regina Elena National Cancer Institute of Rome to evaluate the efficacy of alternating intraperitoneal (IP) recombinant alpha-2-interferon (r-alpha 2-IFN) and cisplatin (DDP) as salvage therapy for less than or equal to 5 mm residual-disease (RD) ovarian carcinoma. Fourteen assessable patients entered the study. All had received prior chemotherapy (11 with DDP-based regimens); five patients had macroscopic RD (less than or equal to 5 mm), and nine had microscopic RD (histologically positive random biopsies and/or positive cytology and immunocytochemical tests). The response to IP immunochemotherapy was evaluated by laparotomy. Pathologic complete remissions (PCRs) were achieved in seven patients (50%) who have remained free of disease with a median follow-up of 22+ months (range, 11+ to 30+ months). Six patients achieved a stable disease and one presented disease progression. With the exception of chemical peritonitis-induced adhesions, no limiting toxicity was observed. The results obtained in this small, highly selected series demonstrate that a high PCR rate may be obtained with IP immunochemotherapy with DDP and r-alpha 2-IFN as salvage therapy in residual ovarian carcinoma less than or equal to 5 mm after first-line chemotherapy also including intravenous (IV) DDP. Larger comparative studies must be conducted to establish the potential role of IP DDP and r-alpha 2-IFN as compared with either of the single treatments. PMID- 2189954 TI - A prospective randomized trial comparing MVAC and CISCA chemotherapy for patients with metastatic urothelial tumors. AB - To evaluate the relative efficacy of cisplatin, cyclophosphamide, and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) (CISCA) versus methotrexate, vinblastine, Adriamycin, and cisplatin (MVAC), a prospective randomized trial was performed in patients with advanced metastatic urothelial tumors. Patients were stratified by histologic disease type and degree of tumor dissemination. Equal distribution of the clinical characteristics was achieved. One hundred ten patients with metastatic disease of the urinary tract (86 bladder, 16 renal pelvis, seven ureter, one prostatic urethra) met eligibility criteria and were enrolled on study. These represented 82% of the total patients seen during the study period in the Section of Genitourinary Oncology who met the eligibility criteria. The combined complete and partial response rate was significantly higher for patients treated with MVAC than for those treated with CISCA (65% v 46%; P less than .05). The survival duration of MVAC-treated patients was significantly longer than that of CISCA-treated patients (mean, 62.6 weeks; median, 48.3; range, 5.0+ to 162.3+ v mean, 40.4 weeks; median, 36.1; range, 7+ to 147.1+). We conclude that MVAC chemotherapy is superior to CISCA chemotherapy, achieving a higher response rate and a longer survival for equivalent patients with metastatic urothelial tumors. PMID- 2189955 TI - Recombinant erythropoietin therapy in cancer patients. PMID- 2189956 TI - Chemotherapy for advanced aggressive lymphoma: more is better ...isn't it? PMID- 2189957 TI - Erythropoietin for the treatment of anemia of malignancy associated with neoplastic bone marrow infiltration. AB - This clinical trial was performed to study the effects of intravenously (IV) administered recombinant human (rh) erythropoietin (EPO) at escalating doses (150, 300, and 450 U/kg, administered as an IV bolus injection, twice weekly, for 6, 4, and 4 weeks, respectively) in five patients with low-grade non-Hodgkin's lymphoma (Ig NHL) and bone marrow involvement and one patient with multiple myeloma (MM). All patients were anemic due to underlying disease. None of the patients had a history of bleeding, hemolysis, renal insufficiency, or other disorders causing anemia in addition to bone marrow infiltrating malignancy. Endogenous EPO serum levels were significantly increased in all patients (74 to 202 mU/mL). Five patients (one MM, four small-cell lymphocytic [SCLC] NHL) showed a dramatic increase of hemoglobin (Hb), hematocrit (Hk) and RBC count becoming obvious on the second EPO dose level. Initial ferritin serum values, which were high mostly due to polytransfusion, were significantly reduced in responding patients. Erythropoiesis of one patient with extensive follicular mixed (fm) NHL did not respond to EPO treatment. Platelet (PLT) count increase (greater than 75% above starting levels) during and following EPO therapy was observed in one patient with MM. Adverse events due to EPO therapy have not been recorded. These findings point out a previously unrecognized capacity of EPO given at pharmacologic doses to stimulate erythropoiesis in patients with anemia due to bone marrow infiltration by neoplastic lymphocytes in spite of enhanced endogenous EPO expression. PMID- 2189958 TI - Results of the vincristine, doxorubicin, and dexamethasone regimen in adults with standard- and high-risk acute lymphocytic leukemia. AB - One hundred five untreated adult patients with acute lymphocytic leukemia (ALL) were entered on the vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and Decadron (dexamethasone; Merck Sharp and Dohme, West Point, PA) (VAD) regimen. Induction therapy with VAD and VAD plus cyclophosphamide (CVAD) was followed by a 2-year rotating maintenance program with multiple antileukemic combinations, and included early intensifications with Adriamycin and high-dose cytarabine (ara-C) and a late intensification with cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) followed by autologous bone marrow transplantation (BMT). Duration of therapy was 24 to 30 months. Eight-eight patients (84%) achieved complete remission (CR) with VAD CVAD, and 94 (90%) ultimately had CR with continuation of the maintenance as planned. Induction mortality was 3%; only half of the patients required prolonged hospitalization of 1 week or longer, or intravenous antibiotics. Maintenance therapy was given to 79 patients, while nine with histocompatibility locus antigen (HLA)-matched related donors underwent allogeneic BMT. The median remission duration was 22 months, and the median survival was 19 months. Factors associated with significantly worse CR rates were older age, the presence of hypoalbuminemia or hyperbilirubinemia, L2 or L3 morphology, and myeloid markers on leukemic cells. Those associated with significantly worse remission durations were the presence of elevated leukocyte or absolute peripheral blast counts, Philadelphia chromosome (Ph)-positive or B-cell ALL, L2 morphology, and more than one course to achieve CR. Patients could be divided into standard-risk ALL (28% of patients) and high-risk ALL (72% of patients) with long-term remission rates of 70% versus less than 30%. The 26 patients who underwent CBV autologous BMT had similar long-term outcome compared with 21 patients who did not (older age, medical contraindications, or socioeconomic problems). The presence or absence of myeloid markers on leukemic cells did not affect long-term prognosis. We conclude that VAD therapy is a well-tolerated effective induction regimen. High-risk ALL patients require alternative maintenance investigational approaches. PMID- 2189959 TI - Human pancreas scintigraphy using iodine-123-labeled HIPDM and SPECT. AB - The pancreatic affinity of iodine-123-labeled HIPDM (N,N,N'-trimethyl-N'-(2 hydroxy-3-methyl-5-iodobenzyl)-1,3-propane diamine) ([123I]HIPDM) was studied in 18 cases (5 normal volunteers, 7 cases with pancreas cancer, and 6 with chronic pancreatitis). In the normal cases, the pancreas was visualized in the planar images as early as 3 hr, and again at 20 hr postinjection. Single-photon emission computed tomography (SPECT) performed following 3-hr planar scintigraphy, provided excellent pancreas images without an overlap of activity in the liver or spleen. The mean pancreas-to-liver (P/L) ratio was 1.26 +/- 0.22 in normal controls. With the exception of one case of massive calcification in the pancreas, the entire pancreas could be observed in the cases with chronic pancreatitis, but the P/L ratio was 0.74 +/- 0.15, significantly lower than that of normal cases. Defective areas of the distal portion of the pancreas were clearly seen in those with cancer of the pancreas. The results of our study indicate that [123I] HIPDM may have clinical potential as a human pancreas imaging agent. PMID- 2189960 TI - Pharmacologic stress with dipyridamole: how lazy can one be? PMID- 2189961 TI - F(ab')2 fragments versus intact antibody--an isodose comparison. PMID- 2189962 TI - Of monoclonal antibodies and thrombus-specific imaging. PMID- 2189963 TI - One step forward with nonspecifically-specific monoclonal antibodies. PMID- 2189964 TI - Radionuclide detection of primary pulmonary osteogenic sarcoma: a case report and review of the literature. AB - A healthy elderly white man was admitted for right inguinal herniorrhaphy. Preoperative chest x-ray revealed a large mass in the lower lobe of the left lung. CT-directed needle biopsy was nondiagnostic. Technetium-99m methylene diphosphonate (99mTc-MDP) bone scan revealed intense soft-tissue activity in the lower left hemithorax with no evidence of abnormal activity in the osseous skeleton. Because of the degree of uptake in the lesion, a presumptive diagnosis of extraosseous osteogenic sarcoma was made. The patient had a left lower lobectomy and the lesion was diagnosed as an osteosarcoma of primary pulmonary origin. PMID- 2189965 TI - SNM selects Dah-Ren Hwang, PhD, as 1990 Berson-Yalow Award winner. PMID- 2189966 TI - SNM awards Mallinckrodt Fellowship to cardiovascular physician. PMID- 2189967 TI - Measuring and interpreting organizational culture. AB - Organizational culture is an abstract, yet potent managerial concept. With roots in several disciplines, several perspectives and definitions of organizational culture have emerged. One perspective focuses on norms and expectations within the organization. In this article, the authors present a quantitative approach to measuring and interpreting organizational culture based on established norms and expected behavior. PMID- 2189968 TI - Nurse decision-making influence. A discrepancy between the nursing and hospital literatures. AB - The associations between participative management and nurse absenteeism, and between work autonomy and nurse turnover, are found to be more negative in nursing than in hospital administration publications. These differences are congruent with what may be different stances of nursing and hospital administration on the subject of nurse decision-making influence. Implications of the apparent discrepancy between the nursing and hospital literatures are discussed. PMID- 2189969 TI - Synergism in work site adoption of employee assistance programs and health promotion activities. AB - As workplaces increasingly adopt proactive programs directed toward employee health issues, the interrelation between different programs becomes an important issue. Of interest here is the "synergy" in patterns of program adoption between employee assistance programs (EAPs) and health promotion activities (HPAs). We utilize the 1985 National Survey of Worksite Health Promotion Activities (N = 1358) for analyses of the dual presence of EAPs and HPAs, and in multivariate analyses we consider factors affecting such dual presence. The data suggest that synergy occurs, with EAP adoption appearing to influence HPA adoption to a greater extent than the reverse. In multivariate analyses, synergy is confirmed by the finding that, among a variety of relevant organizational characteristics, EAP presence and HPA presence are the best predictors of each other's presence. The analyses also indicate that there is minimal commonality in program ingredients across organizations reporting the presence of HPAs. Implications of the data for the future development of these two programming strategies are discussed. PMID- 2189970 TI - Comparison of the dimensional stability of two waxes and two acrylic resin processing techniques in the production of complete dentures. AB - Two base plate waxes and two denture processing techniques were independently compared for dimensional stability. Occlusion rims were constructed from extra hard and medium soft base plate waxes and teeth were set. Acrylic resin bases were processed by a trial packing technique, and a continuous injection system. Tooth movement was measured in the horizontal and vertical planes to assess wax and denture base dimensional changes at various steps in the process, and after 1, 3, and 8 weeks of denture base immersion in water at room temperature. Posterior palatal border adaptation, incisal pin opening and loss of centric occlusion contacts, were also measured. Results showed there were no significant differences between the two waxes as determined by tooth movement in the horizontal and vertical planes. In comparison to the trial packing technique, the continuous injection system showed significantly smaller changes for incisal pin opening and loss of centric occlusion, and better adaptation of the posterior palatal border to the cast. Measurement of tooth movement in the horizontal and vertical planes showed no significant differences between the two processing techniques for times prior to immersion in water, whereas after 8 weeks immersion the continuous injection technique showed smaller dimensional changes, relative to the original dimensions at the time of investing. PMID- 2189971 TI - A laboratory examination of the behaviour of cast cobalt-chromium clasps. AB - Cast cobalt-chromium clasps, long and short, tapered and untapered, were studied. It is shown that the behaviour of apparently identical clasps is inconsistent. Permanent deformation appears to commence during the first month of wear, and after 6 months' wear the retentive quality of almost all of the clasps is impaired. PMID- 2189972 TI - Clinical evaluation of two posterior composite resins: two-year results. AB - Two composite resins were evaluated for clinical acceptability as restorative materials in Class I and II cavities over a 2-year-period. In addition, dispersed phase alloy was evaluated for comparison. All restorations were assessed for anatomical form, marginal integrity and marginal leakage using modified United States Public Health Service (USPHS) criteria. At the 2-year recall, 96% of the composites and 100% of the amalgams were rated 'alpha' or 'bravo', using the parameters of assessment defined in this study. However, a significant number of shifts from the baseline, within the level of acceptability, had occurred. The two composites showed the greatest number of shifts for anatomical form and marginal leakage, while there were no differences between the composites and the amalgam for shifts in marginal integrity. Although a very high level of acceptability was determined for all of the materials, the frequency of rating change within categories for the composites was a cause of concern with regard to their long-term clinical use. PMID- 2189973 TI - The influence of spacers on forces exerted on the abutment teeth of complete mandibular overdentures. AB - The avoidance of lateral forces on overdenture retainers is essential to prevent pathological change in the supporting tissues of the root abutment. In this study, the influence of spacer thickness on the vertical and lateral forces exerted on overdenture abutments was examined clinically. Two subjects with an edentulous maxilla, two canines and a left first premolar remaining in the mandible were selected for the experiment. The anchor type attachment was embedded in the left canine portion of the denture base. The transducer used for the previous study (Ogata et al., 1990), was embedded in this left canine portion. The transducer could detect the magnitude and direction of lateral forces exerted on an abutment tooth parallel to the Camper's plane. The other transducer was embedded in the left first mandibular premolar area, and could detect vertical forces exerted on the abutment tooth perpendicular to the Camper's plane. Furthermore, the transducer could change the space between a denture base and an abutment tooth to 1.5 mm, 0.6 mm or 0.3 mm. Therefore measurements could be made in the same way as if three experimental dentures had been used with a different thickness spacer. Recordings of forces were taken during food chewing, using each spacer on the day of denture insertion and twice at intervals of 1-2 weeks thereafter. The results demonstrated that as spacer thickness decreased, the magnitude of the lateral forces decreased, while the magnitude of the vertical forces increased. These findings suggest that a large part of the lateral component of forces exerted on an abutment tooth could be converted into a vertical component by using a thinner spacer. PMID- 2189974 TI - Blood pressure and cerebral ischemia in very low birth weight infants. PMID- 2189975 TI - Pertussis vaccine and injury to the brain. AB - A syndrome of pertussis vaccine encephalopathy was first reported 56 years ago. Analysis of the recent literature, however, does not support the existence of such a syndrome and suggests that neurologic events after immunization are chance temporal associations of neurologic conditions that occur in the target age group, even in the absence of immunization. Population-based studies do not prove a causal relationship with acute encephalopathy. There are no consistent neuropathologic findings suggesting a specific pathophysiologic process, and hypotheses concerning possible mechanisms of damage are not supported by reproducible studies in children. No acceptable animal model exists. There clearly is an increased risk of a convulsion after diphtheria-tetanus-pertussis immunization but no evidence that this produces brain injury or is a forerunner of epilepsy. Studies have also not linked immunization with either sudden infant death syndrome or infantile spasms. PMID- 2189976 TI - Hydration during the first days of life and the risk of bronchopulmonary dysplasia in low birth weight infants. AB - We conducted a case-control study of antecedents of bronchopulmonary dysplasia (BPD) in 223 infants enrolled in a prospective, randomized clinical trial of phenobarbital prophylaxis for intracranial hemorrhage. The trial took place at three Boston neonatal intensive care units between June 1981 and April 1984. The 76 babies with BPD had radiographic evidence of the condition and required oxygen therapy for 28 days or more. All 147 control babies survived until day 28 of life without meeting either of these criteria for BPD. Compared with control infants, those with BPD received greater quantities of total, crystalloid, and colloid fluids per kilogram per day in the first 4 days of life. In addition, infants with BPD generally had a net weight gain in the first 4 days of life in contrast to the normal pattern of weight loss seen in control infants. Finally, the infants with BPD were more likely to be given a clinical diagnosis of patent ductus arteriosus and to have received furosemide on days 3 and 4 of life. From these observations we infer that early postnatal phenomena such as excessive fluid therapy may be important in the pathogenesis of BPD. PMID- 2189977 TI - Cerebrospinal fluid values in the very low birth weight infant. AB - The cerebrospinal fluid values obtained in the first 12 weeks of life from 43 infants with birth weights of 1500 gm or less were analyzed to determine the ranges for leukocyte count and chemistry values. All these neonates had birth weights appropriate for gestational age, negative cerebrospinal fluid culture for bacteria, and no evidence of intracranial bleeding by head ultrasound examination. The mean birth weight was 1002 gm (range 550 to 1500 gm), and mean gestational age was 27 weeks (range 24 to 33 weeks). The mean cerebrospinal fluid leukocyte count was 5 cells/mm3 (range 0 to 44 cells/mm3); leukocyte differential was 7% polymorphonuclear leukocytes (range up to 66%) and 85% mononuclear leukocytes (range 13% to 100%). Additional values included protein concentration, 142 mg/dl (range 45 to 370 mg/dl); and glucose, 60 mg/dl (range 29 to 217 mg/dl). Knowledge of these measurements should help in the interpretation of the cerebrospinal fluid values of the very low birth weight infant undergoing examination of a central nervous system disorder. PMID- 2189978 TI - White matter necrosis in very low birth weight infants: neuropathologic and ultrasonographic findings in infants surviving six days or longer. AB - We describe the neuropathologic and ultrasonographic findings in 22 very low birth weight infants (mean weight 948 gm) who survived at least 6 days and for whom cranial ultrasonography had been performed three or more times in life. White matter necrosis was found in 15 of the 22 subjects and was judged chronic (5 days' duration or longer) in seven subjects. The most common pattern was diffuse necrosis of hemispheric white matter, found in 10 of 15 infants; restriction of necrosis to the periventricular region was found in only three infants. The classic histologic features of periventricular leukomalacia were absent from 7 of the 15 infants with necrosis. Seventeen infants had intraventricular hemorrhage, but extension of ventricular blood into white matter unaffected by infarction was not found. Two ultrasonographic features were associated with white matter necrosis: increased parenchymal echogenicity and ventricular enlargement. One or both of these findings were present in 67% of infants with white matter necrosis, in 90% of infants with diffuse necrosis, but in no infant without necrosis. Increased parenchymal echogenicity was seen in all four infants with hemorrhagic necrosis, in 60% of infants with diffuse necrosis, but in none of the five infants with localized necrosis. We conclude that the very small infants now dying in nurseries have a form of white matter damage that is more extensive than, and in some cases histologically different from, periventricular leukomalacia as originally described. Ultrasonography as used in this study identified most but not all infants with pathologically verified white matter necrosis. PMID- 2189979 TI - Medical management of chronic suppurative otitis media without cholesteatoma in children. AB - To determine whether systemic administration of antibiotics may eliminate or reduce the need for tympanomastoid surgery in chronic suppurative otitis media without cholesteatoma, we undertook a randomized, prospective study comparing three regimens: (1) daily suction and debridement, with intravenous administration of mezlocillin until 3 days after the discharge stopped, (2) daily suction and debridement, with intravenous use of ceftazidime until 3 days after the discharge stopped, and (3) daily suction and debridement without antibiotics. No topical antimicrobial agents were used during the study. Fifty-one patients were included, and 48 children completed the study. The duration of discharge from the ear before treatment was 2 to 123 months (median 20 months). In 26 patients (51%), the disease was bilateral. Aerobic cultures, obtained with the Alden-Senturia middle ear aspirator, yielded Pseudomonas aeruginosa in 98%, enteric gram-negative bacilli in 33%, staphylococci in 25%, and Haemophilus influenzae in 12%. The first 33 patients were randomly assigned to one of the three regimens. In the 21 patients treated with suction and antibiotics (either mezlocillin or ceftazidime), the discharge stopped completely, versus in only 1 (8%) of 12 patients in the suction-only regimen (p less than 0.01). Therefore the following 18 patients were randomly assigned to one of only two groups, which included the two suction-and-antibiotic regimens. In all patients treated initially with antibiotics, discharge stopped after 4 to 18 days (mean 12.0 days), but 25% needed treatment for greater than 14 days. Amoxicillin prophylaxis was administered to 27 (56%) of the patients after completion of therapy. All patients were followed for 6 months. Drainage recurred in 12 (25%) patients during the first 3 months after the study. The recurrence rate was not affected by the antibiotic regimen, the patient's age, the duration of drainage before initiation of antibiotic therapy, or prophylaxis. We conclude that intravenous wide-spectrum antibiotic therapy in conjunction with daily suction and debridement is efficacious for the treatment of chronic suppurative otitis media without cholesteatoma. PMID- 2189980 TI - Brain tumors in childhood: implications for nursing practice. AB - Pediatric brain tumors are the most common solid tumor and the second most common neoplasm in childhood. Confirmation of diagnosis includes visualization of the tumor on a computed tomographic or magnetic resonance imaging scan. Treatment includes surgical resection or biopsy for confirmation of tissue diagnosis, with observation, radiation, and/or chemotherapy, depending on the tumor's pathology. The care of the child with a brain tumor involves a large multidisciplinary health care team. Nurses and nurse practitioners/clinicians are consistent members of the team that cares for the child and family throughout the course of the illness. Their intervention as advocates and educators in a liasion role between the patient/family and various members of the medical team is critical for the patient and family throughout the course of the illness. PMID- 2189982 TI - Assessment: what role the assessor? AB - The advent of automated assessment contains the seeds of both threat and promise for professional assessors. Placing the problem in the historical and sociological contexts, this article examines computer-based test interpretation (CBTI) and the frequently misunderstood role of actuarial data in relation to it. I argue that sound clinicianship is central not only to the development of adequate CBTI systems, but also to the systems' appropriate and skillful use in practice. When properly utilized by otherwise well-qualified clinicians, CBTI can substantially enhance practice. PMID- 2189981 TI - Microwave heating of infant formula and breast milk. AB - Heating infant formula and breast milk in a microwave oven has become a common practice in many households. A review of the literature is presented to ascertain if there is evidence to support the safety of this practice, as well as to determine if microwaving affects the nutritional content of the heated milk. The results of a local community's survey are presented, which assesses parental use of microwave ovens in the heating of infant formula and parents' knowledge of the potential hazards of this practice. PMID- 2189983 TI - Earliest memories and the dynamics of delinquency: a replication study. AB - A previous study of early childhood memories (EMs) with a sample of 15 delinquents and 18 nondelinquent controls successfully identified 80% of the delinquents and 100% of the nondelinquents. Our study used 71 delinquents and 71 nondelinquent controls matched for age, whereas gender (male) and geographical area were held constant. Socioeconomic status (SES) was restricted to middle class and above. Several refinements were also made to the previous EM scoring system to make it more useful to clinicians, and four EMs were elicited rather than two in the prior study. Predictive results with a discriminant analysis were consistent with those from the previous study and were highly significant--81.7% were correctly classified as delinquents and 95.8% as nondelinquents. The study effectively validates the use of the EM scoring system for this population. The results are discussed from the standpoint of the Cognitive-Perceptual approach to EMs and current models of delinquency. PMID- 2189984 TI - Cohort differences in Hand Test performance: a time lagged analysis. AB - In order to examine the impact of cultural differences (cohort and/or time of measurement) on the intrapsychic processes of older adults, two samples (1976, n = 102; 1986, n = 88) of older persons were compared with regard to their Hand Test (HT; Bricklin, Piotrowski, & Wagner, 1962; Wagner, 1983) performance. Relative to those studies investigating cultural effects in personality at the socioadaptational level (Neugarten, 1977), no research to date has examined this issue utilizing projective methods of assessment. Time-lagged analyses of HT scores of these two samples of elderly adults suggested that there appear to be clear age-related variance in HT performance for both content and derived HT variables. Age-related within-sample variability for most HT scores supported this interpretation. These findings are in contrast to those utilizing more standardized, nomothetic measures of personality functioning that suggest stability of personality in adulthood. PMID- 2189985 TI - Hand Test characteristics of severely behavior handicapped children. AB - The Hand Test was administered to 98 severely behavior handicapped (SBH) children and a matched control group of public school children. The withdrawal score and associated variables, indicative of severe psychopathology, differentiated the two groups. In addition, a qualitative analysis of the SBH protocols tentatively suggested a preponderance of four behavioral types that could be described as the underproductive, perseverative, psychotic and impulsive child. Implications of these findings are discussed. PMID- 2189986 TI - Amyloidosis. AB - The authors present a review of amyloidosis and its classification and clinical presentations. They also discuss its diagnosis and treatment, and present a case of amyloid deposition in the plantar weightbearing aspects of the feet, which exemplifies the classic clinical findings. PMID- 2189987 TI - Diabetic neuroarthropathy of the foot and ankle. AB - A review of medical literature reveals that there is inconsistency in the reported incidence of Charcot joint disease or neuroarthropathy in the diabetic foot. There is also controversy as to which articulations are most commonly afflicted. Radiographs of 21 patients with bilateral diabetic neuroarthropathy were reviewed to determine the distribution of joint disease in the foot and ankle. Many patients had multiple sites of joint involvement. The results of this study show that the incidence of metatarsophalangeal joint involvement has been greatly underestimated. PMID- 2189988 TI - Significance of capillary basement membrane changes in diabetes mellitus. AB - Diabetes mellitus is a disease in which the capillary basement membranes are substantially altered. This diabetic microangiopathy is characterized by a thickening of the basement membrane and changes in its permeability characteristic due to a disturbance in the production and distribution of its functional components. Glucose metabolism and insulin imbalance have been implicated in these basement membrane modifications. The authors describe normal capillary basement membrane architecture and then discuss how pathologic changes caused by diabetes mellitus are related to diabetic foot pathology. PMID- 2189990 TI - Preoperative and perioperative anesthesia considerations for the diabetic patient. AB - Surgery involving diabetic patients requires special consideration of the possible effects of anesthesia. The authors discuss factors that affect the choice of anesthetic agent and recommendations for preparing the diabetic patient for surgery, along with potential complications. PMID- 2189989 TI - Naftifine cream 1% versus clotrimazole cream 1% in the treatment of tinea pedis. Naftifine Podiatric Study Group. AB - Fifty-seven subjects with tinea pedis applied naftifine cream 1% or clotrimazole cream 1% to affected areas twice daily for 4 to 6 weeks in a double-blind, randomized trial. Throughout the study, more naftifine-treated than clotrimazole treated subjects were mycologically cured and globally improved, although differences were not statistically significant. Similar trends favoring naftifine were observed in the resolution of signs and symptoms. Treatment differences noted as early as week 2 suggest that naftifine may have a more rapid onset of action than clotrimazole. PMID- 2189991 TI - Bilateral congenital absence of the fibula. AB - The syndrome caused by congenital absence of the fibula has a number of pathologic abnormalities frequently associated with it, which are illustrated by the case reported. Postsurgical therapy on the involved extremity should take into account the patient's lack of joint motion within the tarsal region. With this in mind, special shoes or accommodative insoles, alone or in combination, should be prescribed in order to facilitate an increase in weightbearing activity with minimal discomfort. PMID- 2189992 TI - Women in podiatric medicine. Experience during training. PMID- 2189993 TI - Psychological factors in the antarctic. AB - For the people who live and work in the Antarctic, isolation and extreme physical conditions cause considerable stress. This article reviews psychological research on Antarctic residents, focusing on factors related to the isolation (effective personnel selection, positive adjustment, conflict, and reintegration into the home environment) and factors related to the physical environment (the extreme cold, high altitude, increased radiation, sensory deprivation, and seasonal changes in activity level). Finally, Antarctic research has been applied to the study of future space travel and space station habitation. PMID- 2189994 TI - Flow cytometry and the rheumatic diseases. PMID- 2189995 TI - Diagnostic conundra in the spondyloarthropathies: towards a base for revised nosology. PMID- 2189996 TI - Plain radiographs can be useful in estimating lumbar bone density. AB - On standard lateral roentgenograms of the lumbar spine, a decrease in bone density is said to be detectable only after a bone loss of about 40%. To evaluate this view, we compared findings on plain films with bone mineral content of L1 determined by quantitative computed tomography in 80 healthy subjects with a mean age of 60 years. The highest correlations with bone mineral content were found for the criteria "vertebral density versus soft tissue" (r = 0.5, p less than 0.0001), the "amount of trabeculations" (r = 0.49, p less than 0.0001), and for the "overall" estimate of osteopenia in the vertebra (r = 0.55, p less than 0.0001). Surprisingly, these three radiographic criteria proved to be most helpful in subjects with bone mineral content above 110 mg/cm3 (nonosteoporotic range). We conclude that lateral radiographs of the lumbar spine can provide a rough estimate of bone density in nonosteoporotic subjects which may be helpful in determining when further analysis with more precise methods is appropriate. PMID- 2189998 TI - How to use prognostic factors in axillary node-negative breast cancer patients. PMID- 2189997 TI - Illness cognition and behavior: an experimental approach. AB - The study of illness cognition and behavior has relied primarily on nonexperimental research designs. In this paper we review the results of a program of experimental investigations of psychological reactions to health threats. Most of the studies employ a new experimental paradigm developed to study illness cognition and behavior in the laboratory. The paradigm has been used in several experiments to examine the cognitive and motivational processes underlying reactions to medical test results. A converging series of studies has shown that denial, manifested in a variety of ways, is a common initial reaction to threatening information. In addition, the studies demonstrate that the perceived prevalence of a health disorder is an important determinant of its perceived seriousness. The insights gained from these studies illustrate the complementary roles of basic experimental research and more naturalistic observational research in the formulation of comprehensive theories of health and illness behavior. PMID- 2189999 TI - Interferon alpha-2a and dacarbazine in melanoma. PMID- 2190000 TI - Studies on human CFU-Mix microvolume culture by use of limiting dilution assay. AB - By use of limiting dilution assay we investigated the bipotent and pluripotent hemopoietic progenitor cells (CFU-Mix) from 21 normal adults, cultured for 32 times. The CFU-Mix counts were 35.7 colonies/10(6) bone marrow cells. According to different cellular elements they could be divided into 5 groups, namely GEMM, GE, GL, GMeg and GM phi. It was suggested that differentiation of the stem cell is of stochastic process, influenced by different hemopoietic growth factors and cellular microenvironment. Our model seems to be suitable for studying differentiation of the stem cells. The rates of 3H-TdR and 55 + 59Fe incorporation were determined, and the 2nd day of culture was found to be the delayed stage of cell growth. PMID- 2190001 TI - The new functions of quantitatively medicine simulating and operating by computer (QMSOC). AB - The preliminary results from integration-evaluation on a set of 310 binary relations in current data base of the new research Quantitatively Medicine Simulating and Operating by Computer (QMSOC) are presented in this paper. Through the function derived from the reciprocity in analysis of conditions, subjects and objects, in the given biomedical events, the number of routes for observation of glucagon and insulin was increased by 38.1% and 136.4% over the conventional object-oriented searching, respectively. The intersection operation of condition sets indicates that it is possible through QMSOC to increase markedly the degree of definity of causality of biomedical events. 70 new binary quantitative relations have been created through operator 1, achieving an increment of 22.6% over the total of original binary relations in the data base. The characteristics and the significance of QMSOC are discussed. PMID- 2190002 TI - A comparison of the antimalarial activity of the cinchona alkaloids against Plasmodium falciparum in vitro. AB - The effects of four major cinchona alkaloids: (-) quinine, (+) quinidine, ( )cinchonidine, and (+)cinchonine against Plasmodium falciparum FCQ-27/PNG were studied. The alkaloids were tested in vitro as either single alkaloids, racemic mixtures of stereoisomers, or as an equimolar combination of all four alkaloids. Results indicate (+)quinidine to be most effective and both (+)stereoisomers were more potent than the (-)stereoisomers. Inhibitory concentrations 50% (Ki) of racemic mixtures of stereoisomers were similar to those of the (+)stereoisomers alone. The Ki of four alkaloids in equimolar combination were similar to that of the (-) cinchonidine/(+)cinchonine racemic mixture. A total alkaloidal extract of Cinchona sp. was tested and compared with the pure alkaloids. HPLC analysis indicated that (+)cinchonine, (-)cinchonidine and (-)quinine were present in a ratio of approximately 1:1:2, respectively. The total alkaloid extract, with ( )stereoisomers predominating, was less effective than the four alkaloids in combination. The nature of the interaction between stereoisomers was investigated and appears to be one of addition. PMID- 2190003 TI - Biochemical characteristics and a simple scheme for the identification of Aeromonas species and Plesiomonas shigelloides. AB - The biochemical characteristics of 55 strains of Aeromonas spp. and 16 P. shigelloides of human faecal origin were examined. Results of tests for the production of oxidase, acid from xylose, dulcitol, adonitol, mannitol, or inositol; greenish pigmentation on nutrient agar, and growth in 6.5% NaCl broth were found to be specific and reproducible. However, other tests such as haemolysis on blood agar (BA), production of DNase, amylase, ornithine or lysine decarboxylase; citrate utilization and the methyl red, Voges-Proskauer (MRVP) varied with different strains. On the basis of our results, we propose a simple scheme for the preliminary identification of Aeromonas and Plesiomonas isolates in laboratories with limited resources. We hope that other laboratories will evaluate it to determine its validity. PMID- 2190004 TI - Obstructive jaundice: an unusual presentation of amoebic liver abscess. AB - A case of amoebic liver abscess with obstructive jaundice is described. Treatment with metronidazole resulted in improved general condition while the jaundice continued to increase. The abscess was twice aspirated and a total of 500 ml fluid was obtained with no improvement in the jaundice. A percutaneous catheter was introduced and drained 300-400 ml bile a day, decreasing and stopping over a week. The jaundice progressively improved. PMID- 2190005 TI - A double-blind controlled study of the efficacy of cimetidine in the treatment of the cervical symptoms of gastroesophageal reflux. AB - Globus pharyngeus and post-nasal drip are common patient complaints encountered in general otolaryngologic practice. Although these complaints have been traditionally ascribed to stress and sinusitis respectively, recently it has been suggested that they are secondary to gastroesophageal reflux, either by a direct effect on the pharynx and posterior larynx or by referred sensation along vagal pathways from the lower esophagus. This reflux could alter the motor tone of the laryngoesophagus and contribute to the pathogenesis of dysphonias. If globus and post-nasal drip are secondary to gastroesophageal reflux, then reduction of stomach pH should reduce the frequency and severity of these complaints. To test these hypotheses in a clinical setting, a large population of patients with vocal disorders was analyzed for the incidence of these complaints. Twenty healthy patients with globus and/or postnasal drip were then entered in a double-blind random placebo-controlled study to assay the efficacy of cimetidine in treating these complaints. No significant difference was found between cimetidine and placebo. PMID- 2190006 TI - Consensus conference. Noise and hearing loss. PMID- 2190007 TI - Treating the American tragedy--MDs try to heal the sick homeless. PMID- 2190008 TI - Physician service opportunities abroad. PMID- 2190009 TI - Czechoslovak medicine, a battered child. PMID- 2190010 TI - Working with African nations to improve the health of their children. Combatting childhood communicable diseases. PMID- 2190011 TI - Therapeutic effects of cefpirome, a new cephalosporin, on various models of infections in mice and rats. AB - Cefpirome (HR 810) is a new cephalosporin with a 2,3-cyclopentenopyridine group in the 3-position side chain. It was compared with other cephem antibiotics in protective and therapeutic effects on various experimental infections, systemic and local, in mice and rats. HR 810 had more potent protective effect than ceftazidime (CAZ), cefoperazone (CPZ), and cefotaxime (CTX) on systemic infections induced by Escherichia coli Ec-31, Staphylococcus aureus SMITH, and Serratia marcescens Sm-6 in mice. Against systemic infection with Pseudomonas aeruginosa HR 810 was as effective as CAZ. Mice with leukopenia induced by cyclophosphamide were systemically infected with methicillin-resistant S. aureus (MRSA), methicillin-susceptible S. aureus (MSSA), Enterobacter cloacae, Acinetobacter calcoaceticus, and Enterococcus faecalis. HR 810 was superior to cefuzonam (CZON) and cefmetazole against MRSA and MSSA and was much more active than any other antibiotics tested against E. cloacae and A. calcoaceticus. In the activity against E. faecalis, HR 810 was inferior to ampicillin but superior to CZON. In mice with pyelonephritis caused by E. coli Ec-7, the rank order of activities was HR 810 greater than CAZ greater than CTX greater than CPZ. HR 810 was more effective than latamoxef, CAZ, CTX, and CPZ in improving lung infections induced by Streptococcus pneumoniae HL 438 and Klebsiella pneumoniae Kp-51 in mice. HR 810 was superior to CTX and CPZ and comparable to cefazolin in therapeutic effects on intrauterine infections with E. coli Ec-89 and S. aureus SMITH in rats. PMID- 2190012 TI - [Chemoprophylaxis of ophthalmia neonatorum through vertical infection. Evaluation of Crede's method using ofloxacin and gentamicin]. AB - Crede's method was evaluated using of ofloxacin (OFLX) and gentamicin (GM) to show the clinical significance of chemoprophylaxis against ophthalmia neonatorum occurring through vertical infection. The obtained results are summarized as follows. 1. OFLX and GM were separately instilled using Crede's original method to 260 cases selected from all the cases of delivery encountered in this hospital during a period of 6 months from 1987 to 1988. Both groups had similar backgrounds. 2. OFLX and GM were effective in 123 of 129 cases and in 116 of 131 cases, respectively. No side effects were found. 3. OFLX to which recent isolates of Staphylococci and Escherichia coli from obstetric clinics were sensitive was more effective for the prevention than GM to which many isolates were tolerant. These findings indirectly proved the clinical significance of Crede's method. 4. Cases showing ineffectiveness of the prophylaxis may have been due to nosocomial infections. PMID- 2190013 TI - Prophylactic and therapeutic effects of oral administration of amphotericin B in mycosis associated with hematologic diseases. Study Group of Mycosis in Hematologic Disease. AB - The prophylactic and therapeutic effects of the oral administration of amphotericin B (AMPH) to patients with deep mycosis associated with hematologic diseases were evaluated in an investigation including determination of serum concentrations of the antibiotic. Prophylactic effects were examined in 111 subjects, and the efficacy rates averaged 83.8% at daily doses from 1,200 to 4,800 mg. The efficacy was significantly higher at a dose of 2,400 mg/day than at a dose of 1,200 mg/day (P less than 0.05). The efficacy rate tended to be higher when the length of administration period was 1 month or more. The percentage of the number of days of fever by neutrophil count was significantly less at a daily dose of 2,400 mg than at 1,200 mg in patients with neutrophil count of 1,000 cells/mm3 or less (P less than 0.001). The safety was evaluated in 131 subjects, and adverse effects were found in only 2 cases of nausea for an incidence rate of 1.5%. Therapeutic effects were studied in 12 cases, and efficacy rates averaged 58.3% at daily doses from 2,400 to 7,200 mg. Adverse effects consisted of 1 case of diarrhea among 15 subjects who were evaluated for the safety for an incidence rate of 6.7%. The serum concentrations of the antibiotic were examined in 60 of the prophylactic and therapeutic subjects. Average concentrations of AMPH at 4 hours after the first daily dose of 1,200, 2,400 and 4,800 mg were 0.040, 0.053 and 0.078 micrograms/ml, respectively. Concentrations gradually increased thereafter and reached averages of 0.089, 0.090 and 0.132 micrograms/ml, respectively, for the 3 dose levels on the 7th day. These results indicated that there were no serious adverse effects and serum concentrations were above the Candida MIC values at daily prophylactic and therapeutic doses of 1,200 to 7,200 mg of AMPH. Based on these findings, this drug can be expected to show prophylactic and therapeutic effects with safety in cases of deep mycosis. PMID- 2190014 TI - [Evaluation of norfloxacin in the pediatric field. Pediatric Study Group for Norfloxacin]. AB - Norfloxacin (NFLX, AM-715), a new quinolone antibiotic agent, was evaluated clinically and bacteriologically for its efficacy and safety in pediatrics by a study group organized with pediatricians from all over the country. A summary of the results of the evaluation is as follows. 1. Incidence of NFLX-resistant strains (MIC over 12.5 micrograms/ml) isolated from children with various infections was 1.6% (8/512). One resistant strain was observed among 45 isolates of Staphylococcus aureus, and none among 30 isolates of Pseudomonas aeruginosa. 2. After single oral administration of 1.5-2.9, 3.0-4.8 and 5.1-6.1 mg/kg NFLX in tablet form at fasting, mean peak values of serum concentration of 0.37, 0.56, 0.92 micrograms/ml, T1/2 of 2.5, 2.6, 2.6 hours and urinary recovery rates in 8 hours at 25.3, 25.3, 27.1% were observed, respectively. 3. Clinical effects were studied chiefly in intestinal and urinary tract infections. Among 317 patients from whom pathogens had been isolated, responses to the treatment were excellent in 187, good in 79, fair in 9, poor in 7, and unknown in 35 cases. The overall efficacy rate was 94.3% (266/282) and the efficacy rate for excellent responses was 70.3% (187/266). Among all the 406 patients treated, including those with undetermined pathogens, responses were excellent in 233, good in 106, fair in 11, poor in 11, and unknown in 45 cases. The overall efficacy rate was 93.9% (339/361). 4. Clinical effects of NFLX classified by diseases with identified pathogens were 81.8% (9/11) for acute pneumonia, 80.8% (21/26) for other respiratory infections, 95.8% (23/24) for bacillary dysentery, 98.6% (70/71) for Campylobacter enteritis, 100% (24/24) for Salmonella enteritis, 100% (6/6) for other acute enteritis and 98.1% (104/106) for urinary tract infections. Including other infections as high as 94.3% (266/282) of efficacy rate was obtained in total. There was no significant difference in NFLX efficacies between unidentified and identified pathogens. Thus, the total clinical efficacy rate was 93.9% (339/361). 5. The total eradication rate of 325 pathogens evaluable was 84.3%, with identical eradication rates for Gram-positive cocci (GPC) (43/51) and for Gram-negative rods (GNR) (231/274). 6. The optimal daily dose of NFLX seemed to be in a range between 6.0 and 12.0 mg/kg, and the optimal duration of treatment to be 7 days for children over 5 years old. 7. The clinical efficacy in treating P. aeruginosa infections in 12 patients was 100% (11/11) and the eradication rate was 83.3% (10/12).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2190015 TI - Randomized trial of combination antibiotic therapy in patients with hematological disorders. Hanshin Study Group of Hematopoietic Disorders and Infection. AB - A 3 arm prospective randomized trial was designed to compare the effectiveness of aztreonam (AZT) + clindamycin (CLDM), amikacin (AMK) + AZT and CLDM + AMK as antibiotic therapy for fever in patients with hematological disorders. Between July 1987 and June 1988, one hundred and sixty of the 199 febrile episodes entered in this study were evaluated for response. Underlying diseases were hematological malignancies in 88.8% of the subjects, and there was no statistically significant differences in incidences of the diseases among the 3 groups. Efficacy rates were 64.2% in the AZT + CLDM group, 52.8% in the AMK + AZT group and 35.2% in the CLDM + AMK group. Efficacy rates in those with neutrophil counts was less than 500/microliters before starting the antibiotics were 53.3%, 43.8% and 25.0%, respectively, in the 3 groups. The combination of AZT + CLDM was found to be the most effective even in the treatment of infections associated with febrile neutropenic patients. PMID- 2190016 TI - [Clinical studies on cefteram pivoxil in the treatment of respiratory infections]. AB - Cefteram pivoxil (CFTM-PI), a new ester type cephem antibiotic, was administered at a daily dose of 600 mg to 81 patients with respiratory infections. They included 4 cases of laryngopharyngitis, 5 cases of tonsillitis, 26 cases of acute bronchitis, 13 cases of pneumonia, 10 cases of chronic bronchitis, 1 case of diffuse panbronchiolitis, 14 cases of infected bronchiectasis and 8 cases of infected other chronic respiratory diseases. Clinical effects were excellent in 18 cases, good in 50 cases, fair in 7 cases, and poor in 6 cases, thus, the efficacy rate was 84.0%. Nausea was observed in 2 cases, and diarrhea, vertigo, or fever was observed in 1 case each. The elevation of GOT and GPT values were found in 4 cases and a slight elevation of total bilirubin value was found in 1 case. These adverse reactions, however, were slight in their grades. CFTM-PI appears to be a useful oral cephem antibiotic in the treatment of respiratory infections. PMID- 2190017 TI - [Susceptibilities of Escherichia coli, Salmonella and Staphylococcus aureus isolated from animals to ofloxacin and commonly used antimicrobial agents]. AB - Susceptibilities of Escherichia coli, Salmonella and Staphylococcus aureus isolated from chickens, pigs and cattle to ofloxacin (OFLX) and commonly used antimicrobial agents were investigated. 1. E. coli (28 isolates) demonstrated the highest level of susceptibility of OFLX (MIC 0.10-0.39 micrograms/ml for all the isolates) among all the test drugs. Commonly used antimicrobial agents to which these isolates responded with relatively high susceptibilities (MIC50 0.78-6.25 micrograms/ml) included oxolinic acid (OXA), ampicillin (ABPC), kanamycin (KM) and chloramphenicol (CP) with their MIC50 values in the increasing order as above. Drugs to which these isolates responded with moderate to weak susceptibilities (MIC50 25 approximately greater than 800 micrograms/ml) were doxycycline (DOXY), streptomycin (SM), spectinomycin (SPCM) and sulfadimethoxine (SDMX) in the increasing order of MIC50. E. coli isolates with resistances to all the test drugs other than OFLX and OXA amounted to 7.1-57.1% of the isolates examined and 20 isolates (71.4%) in total. 2. Susceptibilities to OFLX and 4 existing pyridonecarboxylic acid derivatives of E. coli (48 samples) isolated recently from diarrheal pigs were compared. When evaluated in terms of MIC50, the values of OFLX and norfloxacin were both 0.10 micrograms/ml. The values increased by differences of 0.39-3.13 micrograms/ml in an order of OXA, pipemidic acid and nalidixic acid. 3. Salmonella (28 isolates) demonstrated the highest level of susceptibility to OFLX (MIC 0.20-0.39 micrograms/ml for all the isolates) among all the test drugs. The drugs to which these isolates responded with relatively high to moderate susceptibilities (MIC50 0.78-12.5 micrograms/ml) included ABPC, OXA, DOXY, KM, CP and SM with their MIC50 values increasing in this order. The drugs to which the isolates responded with low susceptibilities (MIC50 above 100 micrograms/ml) were SPCM and SDMX. Of all the 28 Salmonella isolates tested, 7.1 32.1% were resistant to all the test drugs other than OFLX and OXA. These resistant isolates amounted to a total of 12 isolates (42.9%). 4. S. aureus (28 isolates) were highly susceptible to OFLX (MIC50 and MIC90 were both 0.78 micrograms/ml). Commonly used antimicrobial agents to which the isolates responded with high to relatively high susceptibilities (MIC50 0.10-6.25 micrograms/ml) were, in the increasing order of MIC50: DOXY, ABPC, tylosin, tiamulin, KM, OXA and CP. Drugs with moderate to low bacterial susceptibilities (MIC50 12.5-100 microns/ml) were SD, SDMX and SPCM. Isolates resistant to all the test drugs except OFLX and SDMX amounted to 3.6-50% of the 28 isolates examined and they totalled 20 isolates (71.4%).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2190018 TI - [Ten cases of an apocrine carcinoma of the breast and a review of cases in the Japanese literature]. AB - To encounter an apocrine carcinoma of the breast is very rare. We have experienced, however, 10 cases of an apocrine carcinoma (0.65%) among 1541 primary breast carcinoma cases. The mean age of the patients was 58.1 years, and the tumor size on palpation ranged from 1.1 to 6.0 cm (mean 3.5 cm). A lymph node metastasis was seen in 5 cases. While one patient determined as being in stage III b of the disease died of the cancer approximately 5 months after surgery, all of other patients are still alive. The prognosis of this type of disease appears to be better than that of a common invasive ductal carcinoma. Thirty-four cases of an apocrine carcinoma have been found in the Japanese literature, this number including our 10 cases. Discussed are the clinicopathological features and the histogenesis of this type of cancer. PMID- 2190019 TI - [A double cancer of the gallbladder and common bile duct associated with an anomalous arrangement of the choledocho-pancreatic ductal junction--a case report and a review of the literature]. AB - Reported is the case of a 65-year-old woman who complained of general fatigue and itching. The cancer of the gallbladder and the common bile duct associated with anomalous arrangement of choledocho-pancreatic ductal junction was diagnosed after examination by ERCP, PTCS, US, and CT. The cancer of the common bile duct had metastasized to the pancreas, the portal vein, and the regional lymph nodes and was unresectable. It is well known that an anomalous arrangement of the choledocho-pancreatic ductal junction is highly associated with a cancer of the common bile duct or the gallbladder. But a case that is associated with double cancers is rare and only 6 cases have been reported in the Japanese literature. In addition to a discussion of this case, the literature is reviewed. PMID- 2190020 TI - [A case report of an acute myelogenous leukemia (FAB M1) with Klinefelter's syndrome]. AB - Reported is the second documented case in Japan of acute leukemia with Klinefelter's syndrome. The patient, a 52-year-old male, was admitted to hospital on July 9, 1983, after complaining of a fever and general malaise. The hematological examinations revealed a WBC count of 14,300/cmm with 32% being leukemic cells. Bone marrow aspiration disclosed a nucleated cell count of 687,000/cmm with 41.6% being leukemic cells consisting of myeloblasts. The endocrinic laboratory data showed a high level of urine gonadotropin and chromosomal studies revealed a 47,XXY karyotype. A diagnosis of acute myelogenous leukemia (M1) with Klinefelter's syndrome thus was derived from these findings. PMID- 2190021 TI - [Peroral endoscopical diagnosis for the early stage of cancer in bilio-pancreatic system]. AB - PCPS (peroral cholangio-pancreatoscopy), a modality of mother and baby scope systems, was very useful for the diagnoses of bile duct tumors. The endoscopical findings and pathological findings obtained on the biopsy specimen collected under the direct view were valuable. For the diagnosis of pancreatic diseases, PMPS (peroral micro-pancreatoscopy), in which ultrathin quartz fibers are used for the baby scope, was useful. By this method, we could observe the inside of the pancreatic duct through an untreated normal papilla. This is very helpful for endoscopical diagnosis of small pancreatic cancers. EUS (endoscopic ultrasonography) was also a useful method for the diagnosis of small pancreatic cancers. EUS could draw the three layers of the common bile duct and gall bladder walls, and could distinguish a cholesterol polyp from a non-cholesterolic one. Combined application of these methods will aid in the discovery of early stages of cancers in the bilio-pancreatic system. PMID- 2190022 TI - [Inflammatory reaction and laboratory tests: interleukin-1]. AB - Recent progress on the study of IL 1 is summarized and depicted, particularly emphasizing the variety of IL 1 function, and the role of other cytokine inducers. While it has been established that IL 1 has a variety of biological functions in vitro and in vivo, some of these functions are not a direct action of IL 1, but may be ascribed to some other cytokines induced by IL 1, since IL 1 can induce IL 6 (as an inducer of acute phase protein), IL 8 (as a neutrophil chemotactic factor), or IL 1 itself. Other important functions of IL 1 in vivo including resistance to bacterial infection, radioresistance and anti-tumor activity are of great interest to determine whether its action is direct or indirect through the induction of other factors, although the importance of IL 1 yet remains. Finally, the bioassay and ELISA assay of IL 1 alpha and IL 1 beta were established. The IL 1 level in serum, amniotic fluids, and synovial fluids from rheumatoid arthritis have been determined and its biological significance has been discussed. PMID- 2190023 TI - [Inflammatory reaction and laboratory tests: IAP (immunosuppressive acidic protein)]. AB - The immunosuppressive acidic protein (IAP), a type of alpha 1-acid glycoprotein has been used as to monitor cancer and inflammation in patients, though it lacks disease specificity. We studied the serum IAP values in 41 patients with renal cell carcinoma. The normal upper limit of serum IAP concentration is 500 micrograms/ml, and a higher value was determined as positive. Serum IAP values and its positive ratios as determined by Robson stage analysis were respectively, 495 + 118 micrograms/ml and 35% (6/17), 757 + 333 micrograms/ml and 90% (9/10), and 921 + 277 micrograms/ml and 100% (14/14), at low (1 + 2) stage, stage 3, and stage 4, respectively. We also studied serum IAP values of the 41 patients above according to Satomi's classification. The positive ratio as 100% (14/14) for the quick type, and 67% (18/27) for the slow type. In addition, we studied the serial serum IAP values in these patients. The serum IAP values decreased to or were within the normal range by one month after operation in 10 patients with curative nephrectomy, while in 8 patients with non-curative nephrectomy abnormally high levels of serum IAP were seen one month after operation except in one case. The serum IAP value was considered as a useful factor in determining the prognosis of patients with renal cell carcinoma. PMID- 2190024 TI - [Inflammatory reaction and laboratory tests: hematologic examination]. AB - The leukocyte count, the differential leukocyte count and the erythrocyte sedimentation rate (ESR) are the more commonly used tests for diagnosing or managing an inflammatory process. Measurements of acute-phase proteins has an advantage over that of the leukocyte count and ESR. Especially microscopic examination of peripheral blood smear can be time consuming, but the simple and inexpensive technique is still clinically useful when a high grade bacteremia is likely to be present. Although the results are examiner dependent, it should be reliable in the proper clinical setting. In the guidelines for the selection of laboratory tests for monitoring the acute phase response, published in 1988, the International Committee for Standardization in hematology (ICSH) considered the biohazzard of ESR. Therefore the ESR should not routinely be performed on blood samples from patients who show a positive test for hepatitis virus or human immunodeficiency virus. The subcommittee for laboratory tests in daily care situations in Japan Society of Clinical Pathology published the "Essential Laboratory Tests" in 1989. We conclude that the differential leukocyte counts and the ESR should be used to follow the activity and response to treatment of certain inflammatory disorders when other objective indicators are not available. PMID- 2190025 TI - [inflammatory reaction and laboratory tests: granulocyte elastase]. AB - The role in the so called inflammatory response of the polymorphonuclear granulocyte elastase (PMN elastase, EC 3.4.21.37) has been well established. Elastase, a neutral protease stored in the lysosomes of neutrophils and monocytes, is extracellularly released during the process of phagocytosis, and bound to alpha 1-proteinase inhibitor (E-alpha 1-PI complex). This complex can be quantified by an immunoassay. PMN elastase has been shown to be a sensitive and specific marker for the early diagnosis of inflammation and prediction of inflammatory complications. PMID- 2190026 TI - [The current aspect of serum creatine kinase in the laboratory medicine]. AB - Two novel immunochemical methods for CK isozyme analysis using monoclonal antibodies were evaluated. One is an immunochemiluminescence method for CK-MB. The other is an immunochemical method for CK-MM isoform. 1) CK-MB: The conventional methods for CK-MB analysis currently used in many laboratories measure enzyme activity, but the immunochemiluminescence method, currently developed, has a completely different principle. By use of a specific monoclonal antibody for CK-MB, it can measure CK-MB as protein dose, including biologically inactive CK-MB. Therefore, we can avoid several error factors in the measurement of CK-MB. This immunochemiluminescence method enables us to observe the true CK MB behavior in the blood stream. 2) CK-MM isoform: The measurement of fluorescence intensity after electrophoresis is a routine method for the analysis of CK-MM isoform (MM1, MM2, and MM3). Recently a monoclonal antibody against the M-subunit of CK-MM isoform has been developed. This antibody can recognize and inhibit the M-subunit, containing a lysine residue at the C-terminal end. Therefore, the application of the monoclonal antibody enables us to measure quantitatively CK-MM isoform without electrophoresis. 3) CK-MM isoform converting factor: CK-MM3 is converted to MM1 via MM2 in the blood stream. The nature of this converting factor is suspected to be a carboxypeptidase-N, but this has not been confirmed. PMID- 2190027 TI - [A determination of anti-insulin receptor antibody in serum--a radioreceptor assay excluded the influence of insulin and anti-insulin antibody]. AB - We studied an anti-insulin receptor antibody (IRAb) assay that excludes the influence of serum insulin and anti-insulin antibody in patients with anti insulin antibody and normal subjects. The placental membranes strongly bound with 125I-insulin at 4 degrees C. The insulin specificity of the radioreceptor assay was confirmed by adding excess non-labeled insulin and other human hormones to the assay system. The strong correlation between the receptor binding reactivity (%) and the anti-insulin antibody levels was noted in the conventional direct IRAb assay (r = -0.95), but not in the present IRAb assay (r = 0.46) in 10 clinical samples. The placental membranes were stable as the target insulin receptor for IRAb assay at -80 degrees C for at least 4 months. A significant difference in IRAb levels was found between 10 patients with positive anti insulin antibody and 20 normal controls (p less than 0.01, student t test). The coexistence of insulin and anti-insulin antibody were removed by absorbance to silicagel and by utilizing the two-step (indirect) assay, respectively. IRAb assay without the influence of serum cofactors showed excellent reproducibilities (CV 4.4% (N = 5) and 12.5% (N = 5) in within and between assay variations, respectively). PMID- 2190029 TI - [A case of Alport syndrome diagnosed by immunofluorescence using a newly defined monoclonal antibody]. AB - We report a case of Alport syndrome. The patient, a nine-year-old boy, showed macroscopic hematuria after an upper respiratory infection seven years ago. Microscopic hematuria with proteinuria was pointed out in routine urinalysis at school. He had no apparent familial history of either progressive renal diseases or deafness. Renal biopsy was performed at the age of eight, and he was diagnosed as focal segmental glomerulonephritis (mild) by light microscopy. Slight irregular thickening of the glomerular basement membrane (GBM) was observed focally by electron microscopy. Both light microscopy and electron microscopic examinations did not indicate a hereditary nephritis. The 28-kilodalton (kDa) monomers of the non-collagenous globular domain (NC-1) of type IV collagen were absent along renal glomerular capillary walls from the patient by indirect immunofluorescence while they were normally observed in glomerular capillary walls from healthy subjects and patients with a variety of non-hereditary glomerulonephritis. It was suggested that immunofluorescence using a monoclonal antibody for the NC-1 domain of type IV collagen is useful in the precise diagnosis of the patients with Alport syndrome. PMID- 2190028 TI - [Histogenesis of the clear cytoplasm in the tumor cells of smooth muscle origin]. AB - Perinuclear clear cytoplasm observed in the light microscopic specimens of the tumor cells of smooth muscle origin is in general, understood as the artefact caused by the formalin fixation. However, the precise mechanisms of the histogenesis of clear cytoplasm are still not clear. We observed the clear cytoplasm directly by mean of the electron microscopy of materials detached from light microscopic specimen. Furthermore, we observed the light microscopic specimens made by varying types of methods, examining whether the clear cytoplasm was present or not. The electron microscopy of materials detached from light microscopic specimens revealed the band-like defects of cytoplasm along the long axes of tumor cells. These defects were thought to result from the falling off of cytoplasm. The 1 mu section of the epon embedded block derived from the paraffin embedded block for light microscopic specimen presented no clear cytoplasm, suggesting that the cytoplasm falls off at the procedure of deparaffinization and staining. Although the specimen of conventional frozen section showed no clear cytoplasm, the specimen made by the frozen sectioning after formalin fixation revealed clear cytoplasm. Consequently, it is thought that the fixation of the tissue before the sectioning makes the cytoplasm fragile, thereafter, the cytoplasm falls off at the procedure of deparaffinization and staining. PMID- 2190030 TI - [A case of mixed connective tissue disease complicated with malignant hypertension]. AB - This case was a 51-year-old woman, who had been diagnosed as having rheumatoid arthritis at some clinic and had been treated with both non-steroidal anti inflammatory drugs and steroid 3 years before visiting our clinic. When she noticed a decrease in visual acuity and general fatigue in June 1985, she was referred to an ophthalmologist of our hospital, and found to have blood pressure of 240/150 mmHg and KW grade IV retinal findings. She was admitted in our department to examine and treat malignant hypertension. On admission, remarkable hypergammaglobulinemia (29.3%), arthralgia, arthral deformity and pericardial effusion were present thus, she was suspected to be suffering from malignant rheumatoid arthritis. Anti-nuclear antibody (64X), anti-nuclear ribonucleoprotein antibody (64X) and anti-RNase sensitive antibody of anti-extractable nuclear antigens (ENA) antibody (81920X) were positive, while anti-RNase resistant antibody of anti-ENA antibody was negative. Immunologically, her condition was consistent with mixed connective tissue disease (MCTD). Since urinary protein was positive and creatinine clearance was 46.0 ml/min, renal function was thought to be diminished. Her chest roentgenogram revealed cardiomegaly (CTR 67.5%) and an increase in pulmonary vascular shadow. An echocardiogram demonstrated the presence of pericardial effusion. Plasma renin activity was 3.3 ng/ml/h and it was suspected that an intrarenal ischemic change resulted in increased renin release from the juxta-glomerular apparatus, leading to the marked hypertension. Treatment was started with prednisolone 60 mg/day during 4 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190031 TI - [Removal of small molecular proteins by push/pull HDF and alleviation of shoulder joint pain]. AB - The purpose of the present study was to compare hemodialysis (HD) and push/pull HDF in terms of uremic substance removal and clinical improvement. The treatment of patients complaining of shoulder joint pain was changed from conventional HD to HD or push/pull HDF using a hemodiafilter with large membrane pores. Push/pull HDF showed significantly greater removal of beta 2-microglobulin (beta 2-m) and other small molecular proteins than HD, and serum beta 2-m was significantly lower in concentration with push/pull HDF than HD. There was a decrease in the shoulder joint pain from push/pull HDF, and the range of upper arm movement thereby increased. However, neither this decrease in pain nor the increase in upper arm movement resulted with HD treatment. Hence, it was concluded that push/pull HDF is a more effective form of therapy. PMID- 2190032 TI - [A case of acute tubulo-interstitial nephritis and uveitis syndrome]. AB - We report herein the case of a 14-year-old female who has acute tubulo interstitial nephritis (AIN) associated with bilateral diffuse uveitis. She was admitted for the evaluation of "proteinuria", following general fatigue and weight loss about 2 weeks ago. Her laboratory data showed mild anemia, hyper gamma-globulinemia, mild proteinuria, and the reduced glomerular filtration rate with the increased urinary excretion of beta 2-microglobulin. The histological examination obtained by renal biopsy showed mild edema and diffuse infiltration of mononuclear cells in interstitium without any glomerular or vascular abnormalities, which were compatible with AIN. As for the etiology of AIN, clinical investigations could not reveal any specific causes, such as bacterial and viral infections, drugs and systemic diseases. About 4 months after the onset of nephritis, she also became to suffer from bilateral diffuse uveitis. Therefore, the diagnosis of the acute tubulo-interstitial nephritis and uveitis syndrome (TINU syndrome) (Vanhaesebrouck et al., 1985) could be confirmed. In her clinical course, it was noteworthy that uveitis relapsed frequently in spite of systemic administration of prednisolone, and it took two years until uveitis cured, whereas the AIN subsided spontaneously prior to the specific treatment. In this case, characteristic findings of granulomatous uveitis was closely similar to those of sarcoidosis, which has been rarely reported in TINU syndrome. In this respect, the involvement of immune processes, especially cell-mediated, was suggested as the possible pathogenesis in this case. PMID- 2190033 TI - Stereotaxic approach to hypothalamic nuclei of the Shiba goat with radiographic monitoring. AB - Practical method was devised for precise approach to hypothalamic nuclei in the Shiba goat. A stereotaxic instrument and a brain atlas with stereotaxic coordinates were developed. For an accurate placement of probes into specific hypothalamic regions a radiographic method was employed in which radio-opaque material was injected into the lateral ventricle and the ventricular outline was depicted. A sagittal diagram showing the arrangement of hypothalamic nuclei in relation to the brain ventricular system was constructed from the transverse stereotaxic atlas. This diagram was revealed extremely useful in pinpointing the target on the radiographs of lateral view. Precision of this method was evaluated in female Shiba goats (n = 4) by comparing radiographically estimated positions of hypothalamic nuclei with those histologically determined. Despite of cranial variability among individual animals these two parameters matched well each other in all the nuclei examined. Furthermore, chronic cannulae were implanted into different hypothalamic structures of one goat and the accuracy of their placement was confirmed histologically. Thus, it was revealed that the stereotaxy by aid of radiography herein described was accurate enough to apply to various neuroendocrinological studies in the Shiba goat. PMID- 2190034 TI - The optimal condition for peroxidase-anti-peroxidase staining of lung tissues in canine dirofilariasis. PMID- 2190035 TI - [Correction of paroxysmal tachycardia using methods of electric cardiac stimulation]. PMID- 2190036 TI - [Restrictive cardiomyopathy]. PMID- 2190037 TI - [Pathology of the cardiovascular system in patients with psoriasis]. PMID- 2190038 TI - [New thrombolytic drugs]. PMID- 2190039 TI - [Relation of the anti-anginal effect and blood serum level of verapamil in patients with exercise-induced stenocardia]. AB - In 9 patients with stable angina pectoris of effort the authors studied the relation between the effect of verapamil in single and regular administration and concentration of invariable preparation and its primary metabolites in the blood serum. Antiischemic effect of verapamil was assessed with use of repeated identical and individual loads on treadmill in combination with ECG monitoring before and at the end of treatment. Linear correlation was established between the effect and concentration of verapamil in the blood serum under the conditions of single and regular administration. In long-term use of verapamil the authors noted a significant increase in the action of a single dose caused by verapamil cumulation in the blood serum. During long-term treatment by verapamil a marked effect was recorded in significantly more high concentrations of the preparation in the blood as compared to a single administration. The main primary metabolites of verapamil failed to affect on antianginal effect both in single and regular administration. PMID- 2190040 TI - [The anti-anginal effect of diltiazem in patients with stable exercise-induced stenocardia and vasospastic stenocardia compared with the effect of nifedipine]. AB - Paired bicycle ergometric tests were performed in 13 patients with stable exercise-induced angina who took a single dose of diltiazem (120 mg) and nifedipine (30 mg). Four patients with vasospastic angina underwent repeat ergometrine tests along with the both drugs given in the same doses. The two drugs significantly increased exercise tolerance: exercise time was increased by 83% with diltiazem and by 41.9% with nifedipine, its capacity was elevated by 78.9 and 30.2%, respectively, the "double product" at the peak of exercise was raised by 17.0 and 18.7%, respectively). With intravenous injection of ergometrine, diltiazem and nifedipine eliminated or delayed the spastic reaction of coronary arteries in most cases. PMID- 2190041 TI - [Comparative study of the effects of verapamil, ethmozin and ethacizine on provoked attacks of atrioventricular nodal reciprocal tachycardia]. AB - 27 patients underwent serial electrophysiological studies by using transesophageal atrial stimulation. A-V nodal reciprocal tachycardia was documented by intracardiac electrophysiological examinations. Sustained tachycardia was induced in all the patients before drug administration. On day 4 after oral verapamil, 320 mg/day, ethmosine, 800 mg/day, and ethacizine, 150 mg/day, the patients were subjected to transesophageal atrial stimulation. An antiarrhythmic effect was regarded to be reached if the authors failed to induced sustained tachycardias again. Verapamil, ethmosine, and ethacizine were found to be beneficial in 21 (78%), 13 (48%) and 21 (78%) patients, respectively. A comparative analysis demonstrated that ethacisine was not inferior to verapamil, but ethmosine produced less effects than verapamil and ethacizine. The crossover and individual efficacy shown by each drug suggests that it is necessary to use the technique of serial testing and to choose beneficial drugs from a possibly wide range of medicaments for each patient. PMID- 2190042 TI - [Biological availability of the new anti-arrhythmia drug allapinin in a tablet form]. PMID- 2190043 TI - [Computed perimetry for the follow-up of optic neuropathy in pseudotumor cerebri]. AB - Computerized static perimetry must be regarded as the method of choice for monitoring the course of optic neuropathy in cases of pseudotumor cerebri. A discrete peripheral visual field depression is the first sign of optic nerve damage. If cranial hypertension persists the visual field depression gradually spreads toward the center. Ultimately central visual acuity deteriorates continuously. If the intracranial hypertension is reduced in good time the visual field defects are largely reversible and optic atrophy can be prevented. PMID- 2190044 TI - [Measurement of the sealing impression during the cerclage operation]. AB - In hypotensive or hypertensive eyes (i.e., in the treatment of perforating injuries), choosing an ideal length for the plaque is often difficult. The goal of the procedure is to achieve a sufficient depth of the impression. However, excessive depth must be avoided, since this could lead to String syndrome and scleral necrosis. On the basis of an analysis of ocular geometry it proved possible to calculate the circumference of the globe in the region of the cerclage, and from this the ideal length of the plaque. When silicone foam plaques are used it is between 70.4 mm when attached close to the muscle insertion and a maximum of 74.1 mm when placed on the equator of the bulb. Basing surgery on this calculation method in more than 300 patients, no complications such as String syndrome, scleral necrosis or secondary glaucoma were observed. A chronic inflammatory reaction to the scleral buckle was seen in three cases. In order to avoid this complication, caused by the enormous volume of the cylindrical silicone plaque, splitting or flattening of the plaque is recommended. PMID- 2190046 TI - The elder Mayo and his Rochester colleagues. PMID- 2190045 TI - Fulminant group A streptococcal infections. Report of two cases. AB - We describe two female patients presenting with spontaneous peritonitis and fulminant Streptococcus pyogenes (Strep. pyogenes) septicemia and shock. Both patients recovered completely upon immediate antibiotic therapy, initially with broad range combination therapy effective against Strep. pyogenes, which was switched to penicillin G when culture results became available. This isolated strain in case 1 was M-type 28, which is the M-type most often isolated from vaginal swabs (as commensal) and from blood from patients with puerperal sepsis. Patient 1 had signs and symptoms of a toxic shock-like syndrome, including rapid onset of fever and shock, skin rash, desquamation of palms and soles, and multisystem involvement with vomiting, diarrhea, myalgia, renal failure, and severe disorientation without focal neurological deficits. PMID- 2190047 TI - Confirmation of lymphomatous pulmonary involvement by immunophenotypic and gene rearrangement analysis of bronchoalveolar lavage fluid. AB - Pathologic diagnosis of pulmonary involvement with lymphoma has traditionally necessitated open-lung biopsy in most cases. Specimens large enough to allow recognition of characteristic cytologic and architectural changes are usually not obtained bronchoscopically. Even when adequate biopsy specimens are available, however, unequivocal differentiation of lymphoma from benign inflammatory proliferative lesions (for example, pseudolymphoma or lymphocytic interstitial pneumonitis) is not possible on the basis of light microscopic findings alone. Pathologists have relied on immunohistologic examinations in which antibodies directed against B-cell and T-cell surface antigens are used to help distinguish benign from malignant lymphoid proliferations. Unfortunately, even immunohistologic findings may be nondiagnostic, particularly in T-cell lymphomas and in cases in which lymphoma is surrounded by a benign reactive lymphocytosis. Recent development of molecular biologic techniques (for example, Southern blotting) has provided the ability to detect a monoclonal population of cells based on detection of rearrangements of the genes that encode either B-cell immunoglobulin proteins or T-cell antigen receptor proteins. This technique is capable of detecting a clone of cells even when they constitute as little as 5% of a lymphoid infiltrate. Bronchoalveolar lavage can provide samples of sufficient size to facilitate Southern blotting. We present the first case wherein pulmonary involvement with a B-cell lymphoma was confirmed by both immunohistologic and molecular biologic studies of bronchoalveolar lavage fluid. PMID- 2190048 TI - Effectiveness research and assessment of clinical outcome: a review of Federal Government and medical community involvement. AB - Because of their concern about the increasing costs of health care, industry and government contractors for health care will attempt to control health-care costs for the foreseeable future. New proposals for cost containment include those that are focused on cost alone--for example, expenditure limits--and those that propose to control costs by limiting medical interventions to those of known efficacy. This latter attempt has come to be known as "effectiveness research." Herein, we briefly review the history of quality assurance and cost-containment efforts in the United States, giving special attention to the current initiative based on effectiveness research. Although the effectiveness research initiative has shortcomings (for example, it will not provide guidance when data are not available), it seems to be superior to the current peer review system because it encourages the development of a knowledge base and deemphasizes punitive measures as a way to ensure quality and control costs. The Omnibus Budget Reconciliation Act of 1989 (Public Law 101-239) establishes a federal agency, the Agency for Health Care Policy and Research, within the Public Health Service to focus on effectiveness research. PMID- 2190049 TI - Endogenous uveitis: current concepts of treatment. AB - The medical treatment of patients with uveitis often necessitates the use of systemically administered drugs, including corticosteroids, cytotoxic agents, and cyclosporine. Because of the potential side effects of these medications, physicians unfamiliar with inflammatory ocular disease may be asked to participate in the care of these patients. The most important criteria on which to base the decisions of when and how to treat patients with uveitis are the site and severity of the inflammation, the degree of visual acuity, and the potential for restoration of vision with treatment. Slit-lamp examination, indirect ophthalmoscopy, and fluorescein angiography are useful for evaluating the loss of vision in patients with endogenous uveitis. The main goal of treatment is to prevent permanent scarring and deterioration of vision as a result of the disease or the drug side effects. Frequent reassessment will help ensure adequate treatment and will minimize adverse drug effects. PMID- 2190050 TI - Cerebrospinal fluid physiology and the management of increased intracranial pressure. AB - Increased intracranial pressure can result in irreversible injury to the central nervous system. Among the many functions of the cerebrospinal fluid, it provides protection against acute changes in venous and arterial blood pressure or impact pressure. Nevertheless, trauma, tumors, infections, neurosurgical procedures, and other factors can cause increased intracranial pressure. Both surgical and nonsurgical therapeutic modalities can be used in the management of increased intracranial pressure attributable to traumatic and nontraumatic causes. In patients with cerebral injury and increased intracranial pressure, monitoring of the intracranial pressure can provide an objective measure of the response to therapy and the pressure dynamics. Intraventricular, intraparenchymal, subarachnoid, and epidural sites can be used for monitoring, and the advantages and disadvantages of the various devices available are discussed. With the proper understanding of the physiologic features of the cerebrospinal fluid, the physician can apply the management principles reviewed herein to minimize damage from intracranial hypertension. PMID- 2190051 TI - Lorenz Bohler: distinguished traumatologist. PMID- 2190052 TI - Mechanical and electrical complications of acute myocardial infarction. AB - Although much of the current enthusiasm in the management of acute myocardial infarction is related to revascularization strategies, mechanical and electrical complications continue to pose a major threat to recovery in some patients. Some of the major complications of acute myocardial infarction are cardiogenic shock, rupture of the free wall and pseudoaneurysm, rupture of the ventricular septum, acute mitral regurgitation, right ventricular myocardial infarction, infarct expansion or extension, pericarditis and tamponade, peri-infarction hypertension, and tachyarrhythmias and bradyarrhythmias. For each of these complications, general guidelines for diagnosis and management are offered. Early, aggressive, and judicious treatment of these complications may substantially decrease the morbidity and mortality associated with acute myocardial infarction. PMID- 2190053 TI - Cardiovascular rehabilitation: status, 1990. AB - Cardiovascular rehabilitation is defined as the process of development and maintenance of a desirable level of physical, social, and psychologic functioning after the onset of a cardiovascular illness. Patient education, counseling, nutritional guidance, and exercise training play prominent roles in the process of rehabilitation. Benefits from cardiac rehabilitation include improved exercise capacity and decreased symptoms of angina pectoris, dyspnea, claudication, and fatigue. Recent pooled data regarding exercise training after myocardial infarction demonstrated a 20 to 25% reduction in mortality and major cardiac events. Exercise training may result in an improvement in systemic oxygen transport, a reduction in the myocardial oxygen requirement for a given amount of external work, and a decrease in the extent of myocardial ischemia during physical activity. The efficacy of modification of risk factors in reducing the progression of coronary artery disease and future morbidity and mortality has been established. Herein we review the history, current practice and results, and future challenges of cardiovascular rehabilitation. PMID- 2190054 TI - Treatment of Frey's syndrome with topical 2% diphemanil methylsulfate (Prantal): a double-blind evaluation of 15 patients. AB - Fifteen patients with severe gustatory sweating after total parotidectomy and facial nerve preservation were asked to take part in a double-blind study. All patients were alternatively treated with topically applied placebo and topically applied 2% diphemanil methylsulfate (an anticholinergic agent). A 10-day period was allowed between applications for return of symptoms. Two-percent diphemanil methylsulfate provided partial relief in 33.3% of patients and total relief in 40% of patients. Involvement of the hairy temporal line region with gustatory sweating was the main reason for failure. Duration of relief varied from 2 to 4 days. The only side effect was dryness of the mouth noted in two patients. PMID- 2190055 TI - A Bayesian method for evaluating medical test operating characteristics when some patients' conditions fail to be diagnosed by the reference standard. AB - The evaluation of a diagnostic test when the reference standard fails to establish a diagnosis in some patients is a common and difficult analytical problem. Conventional operating characteristics, derived from a 2 x 2 matrix, require that tests have only positive or negative results, and that disease status be designated definitively as present or absent. Results can be displayed in a 2 x 3 matrix, with an additional column for undiagnosed patients, when it is not possible always to ascertain the disease status definitively. The authors approach this problem using a Bayesian method for evaluating the 2 x 3 matrix in which test operating characteristics are described by a joint probability density function. They show that one can derive this joint probability density function of sensitivity and specificity empirically by applying a sampling algorithm. The three-dimensional histogram resulting from this sampling procedure approximates the true joint probability density function for sensitivity and specificity. Using a clinical example, the authors illustrate the method and demonstrate that the joint probability density function for sensitivity and specificity can be influenced by assumptions used to interpret test results in undiagnosed patients. This Bayesian method represents a flexible and practical solution to the problem of evaluating test sensitivity and specificity when the study group includes patients whose disease could not be diagnosed by the reference standard. PMID- 2190056 TI - The use of efficiency linear programs for sensitivity analysis in medical decision making. AB - Sensitivity analysis in most medical problems is a complex process involving repeated calculations that can be computationally cumbersome, and its results are only approximate. The authors present a linear program-based approach that reveals the optimum strategies in a decision problem when event probabilities are not known exactly but their value ranges are available. Its application in a clinical decision-making situation is demonstrated. The approach promises to provide a flexible, precise, and computationally efficient technique for sensitivity analysis in medical decision making. PMID- 2190057 TI - A mathematical representation of the expert panel's guidelines for high blood cholesterol case-finding and treatment. AB - The National Cholesterol Education Program (NCEP) for high blood cholesterol case finding and treatment recommended discrete treatments according to the results of sequential measurements of continuous variables (total and low-density lipoprotein cholesterol [LDL-C]). These measurements are subject to intra- and interindividual variability. The authors describe a computer simulation of the NCEP that acknowledges these complexities. The simulation reduces the NCEP into steps, which are represented in a decision tree. The calculation of probabilities at chance nodes takes into account the conditional nature of sequential measurements of blood cholesterol. The simulation tracks medical resource use and estimates LDL-C reductions within 20 strata, each defining 5% of population distribution for LDL-C. This approach enables a detailed representation of the case-finding process--the sequence of blood cholesterol tests and associated cut off values that identify individuals needing more intensive evaluation and treatment. PMID- 2190058 TI - ClinQuery: searching a large clinical database. AB - We designed a user-friendly computer program that permits physicians to use clinical and demographic descriptors to search a hospital's clinical database for purposes of patient care, teaching, and research. For example, the user can identify all admissions in which diabetic ketoacidosis was diagnosed, the serum bicarbonate level was under 12 mmol/liter, and the length of stay exceeded 7 days. Once particular admissions have been identified, all data stored in the computerized record can be displayed. Authorized persons can also request the patient's complete medical record for further study. Over a 5-year period, 895 doctors, nurses, medical students, and hospital administrators used Clin-Query to search the clinical database of Boston's Beth Israel Hospital 3724 times. They displayed detailed information on 72,489 patients and requested the complete medical record 5477 times. Responses to a computer-based questionnaire indicated that 16% of the searches were performed for patient care, 38% for clinical research, 16% for teaching and education, 12% for hospital administration, and 18% for general exploration. We conclude that physicians and allied personnel will repeatedly examine and analyze aggregate clinical information when they are provided with the appropriate tools. PMID- 2190059 TI - Bibliographic retrieval: a survey of individual users of MEDLINE. AB - The National Library of Medicine (NLM) has been providing online access to the MEDLINE database for nearly 20 years. In recent years, there has been a shift in the composition of the user population. Nearly half the online access codes are now held by individuals who conduct their own searches of the database. The NLM has conducted a survey to identify the demographic features of this end-user population, their reasons for searching the database, their methods of access, and their satisfaction with MEDLINE as available on the NLM system. PMID- 2190060 TI - Computer-assisted learning in morbid anatomy. A stimulation of autopsy procedures and death certification. AB - This article describes the objectives, design and performance of a computer program which provides a textual simulation of autopsies. The benefits of using this program to teach medical students about the procedures of autopsy diagnosis is discussed. This form of computer-assisted learning is also useful in introducing medical students to correct death certification: a neglected area of medical education. PMID- 2190061 TI - The coroner--12th and 13th century development of the office. PMID- 2190062 TI - Expression of host resistance to Salmonella typhi and Salmonella typhimurium: bacterial survival within macrophages of murine and human origin. AB - Cell-association of various strains of Salmonella typhi and Salmonella typhimurium with different populations of macrophages was studied. Macrophages were infected, exposed to gentamicin, washed, and counts of viable bacteria protected from gentamicin killing were made. J774A.1 cells, a continuous macrophage-like cell line, were the most permissive, all strains tested achieving similar high recoveries. Virulent S. typhimurium 779C-Sms, but not avirulent S. typhimurium 779C-SmD, survived well in mouse peritoneal macrophages and human monocyte-derived macrophages. Virulent S. typhi Ty2 were killed by mouse peritoneal macrophages, but were able to survive within human monocyte-derived macrophages. Viable counts of clinical isolates of S. typhi within the human monocyte-derived phagocytes were lower as compared with those of S. typhi Ty2. Phagocytosis of opsonized and non-opsonized virulent S. typhi Ty2 and S. typhimurium 779C-SmS by mouse peritoneal macrophages failed to trigger their respiratory burst as assessed by the intracellular reduction of nitroblue tetrazolium dye (NBT). These experiments support the view that the intracellular survival of Salmonella is in part host dependent and specific in nature. They also suggest that virulence influences the survival and intracellular multiplication of Salmonella within macrophages, and that their ultimate fate within macrophages may not be related to oxygen-dependent mechanisms. PMID- 2190063 TI - Cancer and cell wall deficient bacteria. AB - Since the 1920's, a small number of researchers have been quite regularly isolating highly pleomorphic bacteria from the blood and tumors of humans and animals with cancer. These bacteria show characteristics of cell wall deficient bacteria, and can apparently be observed regularly in the blood of cancer patients by darkfield microscopy. Cancer appears to be induced by injecting these bacteria into experimental animals, and some forms of cancer can be prevented by prevaccination with killed bacteria, isolated from experimental animals affected with the specific cancer. The bacteria regularly produce a protein ressembling chorionic gonadotropin hormone, a substance which appears to protect trophoblastic and cancer cells from immune recognition. There is some evidence that a plasmid may be responsible for this property, and even that these bacteria may in some manner be intimately associated with retroviruses. Further studies are proposed to clarify the role these bacteria play in cancer. PMID- 2190064 TI - On the topology of normal chromatids and on their translocations in myelogenous leukemia. AB - After some comments on the topology of chromatids, restructuring of the interphase nucleus is conjectured to depend upon the nuclear vesicle apparatus. These vesicles change the intrinsic shape of chromatids to fit the different topology of the interphase nuclear spheroid. Reciprocal translocations between selected chromatids result whenever the nucleus of malignant cells organizes de novo certain exceptional or emergency differentiation paths. However, the almost unavoidable chimeric genes resulting from these translocations may be less ominous than hitherto suspected. This seems to be the case for chronic myelogenous leukemia, where the bcr-abl chimeric gene lessens the aggressiveness of the primary clone when functioning in the context of myelomonocitic differentiation. Finally, our model estimates the statistical incidences of the bcr-abl chimera. These estimates are found to agree with clinical data better than evaluations from the random mutation theory. PMID- 2190065 TI - Paraneoplastic syndromes. AB - A given cancer is a disease which combines a paraneoplastic syndrome with an invasive tumour capable of giving rise to metastases. Surgeons, radiotherapists, medical oncologists and experimental scientists are primarily interested in the tumour. Tumours of tissues and organs which do not normally produce hormones might, during the neoplastic transformation, begin to secrete hormones or substances able to mimic hormones in their effects on other tissues in the organism. The number of known hormones has increased considerably in the last 20 years. It has been found that even in the absence of clinical signs there are often secretory abnormalities and changes in the hormone balance in cancer. The tumour-paraneoplastic syndrome interaction is bidirectional. That paraneoplastic syndromes are dependent upon the tumour, is universally accepted; the reverse, that the tumour might depend on the paraneoplastic syndrome is not part of the current way of thinking. To treat cancer patients, instead of debating the cause and effect in the tumour-paraneoplastic syndrome pair with the classical idea of acting as close to the cause as possible, it seems better, in all circumstances, to treat both the tumour and the paraneoplastic syndrome, even if only subclinical. PMID- 2190066 TI - Drugs from seaweeds. AB - Extracts from seaweed are of botanical and pharmaceutical interest. They are used in traditional remedies in many parts of the world. A large number of edible seaweeds are consumed by the coastal peoples of Asia. Extracted substances from the plants have antibacterial actions and some of these substances have potential use in mosquito control. Other properties include antifungal activities and growth inhibition of other plants. Several chemical compounds have been isolated and identified. PMID- 2190067 TI - The regulation of cytosolic Ca2+ concentration in a mammalian cell. AB - The assumptions governing the regulation of free Ca2+ in a mammalian cell are presented. There is a possibility that mitochondria, microsomes and plasma membrane play a major role, by regulation of the very low concentration of free Ca2+ in cytosol, as the signal to biochemical activities. The possibility of the loss of very high-affinity Ca2(+)-binding and the number of its sites by preparation has not been taken into consideration in previous hypotheses. PMID- 2190068 TI - Are changes in expression of actin genes involved in estrogen-induced cholestasis? AB - It is postulated that cholestasis associated with high estrogen levels found in women in various conditions, is due to alterations in structure and/or function of the system of actin microfilaments by estrogen-induced changes on expression of actin genes and/or some regulatory actin-binding protein genes. Because bile secretion by hepatocytes is apparently mediated by the microfilamentous system of actin, the proposed hormonally induced dysfunction of this system could be translated to cholestasis. PMID- 2190069 TI - A novel hypothesis for the psycho-modulating effects of lithium: the role of essential fatty acids, eicosanoids and sub-cellular second messengers. AB - Evidence is presented for a novel proposal for the mechanism of action of lithium in manic depressive psychosis. Lithium has well established effects on catecholaminergic--and hormone--stimulated adenyl cyclase activity and on cyclic AMP formation. Although there is conflicting evidence in the literature concerning the effects of the ion on cyclic nucleotide phosphodiesterase, not much is known of the effects of lithium on cyclic GMP. These two second messengers have been proposed to be mutually antagonistic in their actions but that a physiological balance between the two is essential for maintaining homeostasis of the human psyche. An in vivo animal study was undertaken to determine the effects of chronic lithium treatment on the dynamics and kinetics of these two cyclic nucleotides and phosphodiesterase in rat cerebral cortex. From these results, a possible functional coupling mechanism between the two second messenger systems and the effects of lithium are proposed. Lithium by means of its specific site of action, is unique among psychoactive drugs in that it can control both phases of bipolar illness. This point of action is proposed to be the metabolism of free fatty acids where lithium, by altering the availability of precursors for eicosanoid metabolism, is able to modulate both noradrenergic- and cholinergic-dependent pathways. By doing this, the ion is able to reestablish lost control over adrenergic and cholinergic balance critical for thought process and mood stability. PMID- 2190070 TI - Are B lymphocytes involved in allograft/tumor rejection and GVH? AB - Several earlier observations by us and other investigators led us to propose a thesis that B lymphocytes, when activated by a virus, allo-antigen or bacterial protein would enter into effector arm of the immune response and cause allograft and tumor rejection or GVH-type of lesion in immunosuppressed animals. These effector cells may act directly in the process by contact with other cells or liberating cytokines. Such an hypothesis needs further support from experiments involving cancer and transplantation patients' B cells. PMID- 2190071 TI - Differential target dependence in the developing brain: implications for mental retardation. AB - During development of the brain, many neurons exhibit a dependence on other neuronal populations for their survival and differentiation (target dependence). Evidence suggests that some neural pathways are much more dependent on single target neuronal populations for their survival than are others (differential target dependence). This phenomenon has important implications both for animal models of congenital human brain damage and for ideas concerning the aetiology of behavioural abnormalities associated with human mental retardation. Predictions of the neuronal deficits likely to arise from exposure to cytotoxic agents (e.g. ionizing radiation, hyperthermia, viral infection) at a particular time must take differential target dependence into account. It is known that target dependence affects corticopetal pathways involved with the discriminative senses (e.g. vision), more than monoaminergic and cholinergic corticopetal pathways which are believed to be involved with arousal, selective sensory attention, sleep, memory and cortical vasomotor function. Following prenatal damage to superficial layers of the cerebral cortex, this effect of differential target dependence leads not only to a relative hyperinnervation of the cortex with monoaminergic and cholinergic projections, but a specific deficit in visual pathways. The implications of this combined deficit for the behaviour and rehabilitation of the mentally retarded are considered. PMID- 2190072 TI - Hypozincemia during fever may trigger febrile convulsion. AB - Febrile convulsions are generally thought to be induced by metabolic changes during the rise-phase of body temperature. The mechanism by which convulsions are induced, however, is not fully elucidated. In this article, we propose a new hypothesis about the induction mechanism of febrile convulsions that takes into account the hypozincemia during fever. This hypozincemia activates the NMDA receptor, one of the glutamate family of receptors, which may play an important role in the induction of epileptic discharge. PMID- 2190073 TI - Health education, health promotion or drugs? Cholesterol and coronary heart disease. PMID- 2190074 TI - Treatment of menorrhagia by endometrial ablation. PMID- 2190075 TI - Bronchial hyperresponsiveness in two populations of South Australian rural schoolchildren. AB - This report describes the cross-sectional analyses of the results obtained from the first year of a longitudinal study designed to investigate the natural history of bronchial hyperresponsiveness in association with reported respiratory symptoms in children attending the Burra and Kingston Community Schools. Bronchial hyperresponsiveness to methacholine was measured using a modified Yan technique. Prevalence rates of respiratory symptoms were obtained using the Tasmanian Asthma Foundation Questionnaire. Considerable overlap of reported symptoms of asthma and/or wheezy breathing and bronchitis and/or loose and productive cough was observed suggesting that a clear distinction between such symptoms in childhood may not be possible. Analyses of data showed the prevalence of reactive airways in children to be 21.3% in Burra and 22.0% in Kingston. These values were the same as results obtained from an earlier pilot study in Burra and similar to results from Wagga Wagga (19.6%) and Auckland (20.1%) but higher than from Belmont (15.5%) and Villawood (15.3%). Increased bronchial hyperresponsiveness was associated with the reporting of symptoms of asthma and/or wheezy breathing (odds ratio, 5.04; 95% confidence interval, 2.18-11.74) and bronchitis and/or loose and productive cough (odds ratio, 2.28; 95% confidence interval, 1.02-5.13), at any time in the child's life. Of children with no reported symptoms 10% also had demonstrable bronchial hyperresponsiveness. PMID- 2190077 TI - Perineal pain after childbirth. PMID- 2190076 TI - Clinical trials in breast cancer in Australia and New Zealand. Australian-New Zealand Breast Cancer Trials Group. PMID- 2190078 TI - The development of a climate for caring: a historical review of premature care in the United States from 1900 to 1979. AB - The data presented in this review of the history of premature care in the United States is limited to published material available within the local area. Additional manuscripts, records, and oral histories, would provide a more comprehensive perspective. The period from 1900 to the early 1940s represents the beginning of premature care in the United States characterized by efforts to provide an intrauterinelike environment. Energies were focused on the three identified basic needs of temperature support, nutrition, and protection against infection. The idea of caring for prematures in an especially designated area in the hospital evolved, and premature stations or wards were created. Advances in technology resulted in sophisticated systems for providing warmth for infants and some interventions for respiratory support using oxygen and an infant ventilator. The dangers of cold stress during transport were addressed with attempts to provide warmth using an especially designed transport incubator. A revolutionary growth in technology combined with the nationwide coordinated effort for organizing regional care has characterized this past 30-year period of premature care (1950-1980). The infant is now surrounded by sophisticated life-support systems and receives medical care from a much broader knowledge base than was available in the past. The environment for premature care has truly surpassed any expectations that health care professionals of the past may have held when the concept of an incubator emerged. Nursing of premature infants has expanded with the level of sophisticated equipment and the knowledge of the premature infant's physiologic needs. Nurses are no longer the gatekeepers of a sanctuary against infection. They care for the premature and the family by providing support, information, and caring during an emotionally stressful time. As the premature's physiological condition stabilizes, the nurse helps the family learn to care for the infant and thus transfers the responsibility of providing warmth, nutrition, and protection to the parents. Nurses are now gatekeepers of a very special sanctuary--the sanctuary of caring. PMID- 2190079 TI - [Structural-functional organization of the poly[(dG-dT).(dC-dA)] sequence in the genome of eukaryotic organisms]. PMID- 2190080 TI - [Insertion of (dA-dT)n sequences into the regulatory region of the pho5 gene inhibits its expression]. AB - We have studied the effect of some regular sequences namely (dA-dT)n, (dA)n and (dG-dC)n on the Saccharomyces cerevisiae PHO5 gene expression. These sequences were inserted into the ClaI site, located between two phosphate-responsible upstream activating sequences (UAS's). A modified PHO5 gene cloned in vector plasmids was used to transform the pho3, pho5 yeast strain and the level of acid phosphatase expression in various conditions was measured. We show that the insertion of (dA-dT)n blocks, but not (dA)n or (dG-dC)n, leads to the dramatic decrease of PHO5 gene expression in a derepressed state. (dA-dT)n inserts also inhibit the expression of PHO5 gene which was put under the control of heterologous UASgal. PMID- 2190081 TI - [Mechanism of integration of cellular and viral DNA. Possible role of integration in the carcinogenesis]. AB - A model describing the mechanism of linear integration of cellular and viral DNA is proposed. The possible role of cellular DNA integration in the process of human carcinogenesis is considered. PMID- 2190082 TI - [Spontaneous synthesis of colicin]. AB - We studied regularities of the spontaneous synthesis of colicin E1 and its regulatory role in the survival of each cell and the population. For the first time, colicin from spontaneously induced cells was isolated and characterized, and the kinetics of its synthesis determined in a separate cell. It was stated that the time of colicin accumulation in an induced cell and the half-time period of a similar cell exceeds the period of cell doubling by 1.5 and 2 times, respectively. Spontaneously synthesized colicin was shown not to differ from the colicin synthesized by using inductors of the SOS-system of cell reparation. A conception was formulated of a biological system containing both colicinogenic cells with plasmids with encoded proteins of colicin, immunity and lysis on them and competitive plasmid-free cells sensitive or resistant to colicin. Environment dependent colicin synthesis in the system shown is regarded as regulator functioning according to the feed-back principle. PMID- 2190083 TI - [Design of ribozymes]. AB - A review of the data on the synthesis of RNA-fragments with endonuclease activity. The Haseloff and Gerlach model for design of ribozymes and the results of the synthesis of the three new ribozymes targeted against the chloramphenicol acetyl transferase gene transcript are considered. The possibility of the use of a shortened form of Tetrahymena self-splicing ribosomal RNA intervening sequence for the ribozyme design also are discussed. PMID- 2190084 TI - [The effect of bases non-complementary to the template on the efficacy of primer interaction with the Klenow fragment of DNA polymerase I from Escherichia coli]. AB - The comparison of the Km and Vmax values for the primers was carried out. The primers were either completely complementary to the template or contained non complementary bases at different positions with respect to the 3'-end. The addition of NaF, selectively inhibiting 3'----5'-exonuclease activity of the enzyme, was shown to result in the increase of Vmax values by 10% and 30% for complementary and partially complementary primers, respectively, Km values of the latters being unchanged. Km values for d[(pT)10pC] is about 146-fold greater than that for d[(pT)11]. Km values for d[(pT)7pC(pT)2] (20 microM) and d[[(pT)2pC]3pT] (20 microM); d[(pT)4pC(pT)5] (5.0 microM); d[(pC)(pT)7] (1.3 microM) and d[(pT)2pC(pT)7] (1.2 microM) are comparable with those for d[(pT)2] (22 microM), d[(pT)5] (4.1 microM) and d[(pT)7] (1.2 microM), respectively, but not with the decathymidylate d[(pT)10] (0.2 microM). We suggest that it is not the length of the primers but the number of bases in the fragment beginning with the first nucleotide from the 3'-end and ending in the non-complementary base, that determines the efficiency of interaction of the primers containing non complementary bases with the enzyme. The addition of one link to d(pT)n (n less than or equal to 10) resulted in a 1.8-fold increase in the affinity. When 11 less than n less than 25 the affinity is decreased so that d(pT)22-23 have minimal affinity to the enzyme. The primers containing more than 50 units were found to have about the same affinity (calculated on base concentration) as d(pT)10-11. PMID- 2190085 TI - Plasmodium falciparum aldolase: gene structure and localization. AB - A genomic clone was isolated which codes for the fructose bisphosphate aldolase of Plasmodium falciparum. The aldolase gene is interrupted by one intron which divides the coding region into two exons. The first one codes for one amino acid only, the initiation methionine, while the second one encodes the residual 368 amino acids of the protein. The gene, which is represented only once in the genome, is transcribed at high rates as a 2.4-kb mRNA in the P. falciparum blood stage. The aldolase gene encodes a protein of 40,105 Da, which is 61-68% homologous to known eukaryotic aldolases. The protein was expressed in Escherichia coli cells in an unfused and enzymatically active form. Antisera raised against amino acids 9-96 recognize a 41-kDa protein band previously shown to protect monkeys against a P. falciparum infection. These antisera cross-react with aldolases of different species, which confirms the strong conservation of this enzyme during evolution. The aldolase could be localized in the cytoplasm of the parasite as an active and soluble form. An inactive form was found to be associated with the membrane fraction. Digestion data with phospholipase C suggest a membrane association of this polypeptide via a glycosylphosphatidylinositol anchor. PMID- 2190086 TI - Sequence of the 24S alpha ribosomal RNA gene and characterization of a corresponding pseudogene from Trypanosoma cruzi. AB - Two genomic clones which cover a 30-kb region containing the ribosomal RNA cistron from Trypanosoma cruzi have been isolated. The location of the 18S, 24S alpha and 24S beta RNA species within the cistron was determined. The complete sequences of the genes corresponding to the 24S alpha RNA and to a small RNA (S1), as well as two internal transcribed spacers were obtained by sequencing a cDNA and a genomic fragment. A locus containing sequences related to the 24S alpha RNA has been determined. Sequence data and structural characterization of this locus strongly suggest that this region contains a 24S alpha RNA pseudogene. PMID- 2190087 TI - Response to type III polysaccharide in women whose infants have had invasive group B streptococcal infection. PMID- 2190088 TI - The curious case of Acarus crossii. PMID- 2190089 TI - Does the eye grow into focus? PMID- 2190090 TI - The solution for teething troubles. PMID- 2190091 TI - Antibodies against AIDS proteins. PMID- 2190092 TI - Trans-kingdom promiscuity. PMID- 2190093 TI - Three-dimensional structure of the free radical protein of ribonucleotide reductase. AB - The enzyme ribonucleotide reductase furnishes precursors for the DNA synthesis of all living cells. One of its constituents, the free radical protein, has an unusual alpha-helical structure. There are two iron centres that are about 25 A apart in the dimeric molecule. Tyrosine 122, which harbours the stable free radical necessary for the activity of ribonucleotide reductase, is buried inside the protein and is located 5 A from the closest iron atom. PMID- 2190094 TI - Invariant chain association with HLA-DR molecules inhibits immunogenic peptide binding. AB - Class II major histocompatibility complex (MHC) molecules are heterodimeric cell surface glycoproteins which bind and present immunogenic peptides to T lymphocytes. Such peptides are normally derived from protein antigens internalized and proteolytically degraded by the antigen-presenting cell. Class I MHC molecules also bind immunogenic peptides, but these are derived from proteins synthesized within the target cell. Whereas class I molecules seem to bind peptides in the endoplasmic reticulum, class II molecules are thought to bind peptides late in transport. Intracellular class II molecules associate in the endoplasmic reticulum with a third glycoprotein, the invariant (I) chain, which is proteolytically removed before cell surface expression of the alpha beta class II heterodimer. It has been suggested that the I chain prevents peptides from associating with class II molecules early in transport. Preventing such binding until the class II molecules enter an endosomal compartment could maintain the functional dichotomy between class I and class II MHC molecules. We have examined the ability of I chain-associated HLA-DR5 molecules to bind a well characterized influenza haemagglutinin-derived peptide (HAp). The results show that whereas mature HLA-DR alpha beta dimers effectively bind this peptide, the I chain associated form does not. PMID- 2190095 TI - Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160. AB - The development of a vaccine to provide protective immunity to human immunodeficiency virus type 1 (HIV-1), the virus causing AIDS, would be the most practical method to control its spread. Subunit vaccines consisting of virus envelope glycoproteins, produced by recombinant DNA technology, are effective in preventing viral infections. We have now used this approach in the development of a candidate AIDS vaccine. Chimpanzees were immunized with recombinant forms of the HIV-1 glycoproteins gp120 and gp160 produced in Chinese hamster ovary cells, and then challenged with HIV-1. The control and the two animals immunized with the gp160 variant became infected within 7 weeks of challenge. The two animals immunized with the gp120 variant have shown no signs of infection after more than 6 months. These studies demonstrate that recombinant gp120, formulated in an adjuvant approved for human use, can elicit protective immunity against a homologous strain of HIV-1. PMID- 2190096 TI - Prevention of HIV-1 glycoprotein transport by soluble CD4 retained in the endoplasmic reticulum. AB - The envelope glycoprotein (gp120/41) of the human immunodeficiency virus (HIV-1) attaches the virus to the cellular CD4 receptor and mediates virus entry into the cytoplasm. In addition to being required for formation of infectious HIV, expression of gp120/41 at the plasma membrane causes the cytopathic fusion of cells carrying the CD4 antigen. The expression of gp120/41 is therefore an ideal target for therapeutic strategies designed to combat AIDS. Here we show that expression of a soluble CD4 molecule, mutated to contain a specific retention signal for the endoplasmic reticulum, blocks secretion of gp120 and surface expression of gp120/41, but does not interfere with transport of wild-type CD4. By blocking transport of the HIV glycoprotein, this retained CD4 molecule prevents the fusion of CD4 cells that is normally caused by the HIV glycoprotein. Expression of the retained CD4 molecule in human T cells might therefore be useful in the intracellular immunization procedure suggested by Baltimore. PMID- 2190097 TI - Fc receptor phosphorylation during receptor-mediated control of B-cell activation. AB - It is well known that Fc receptors for IgG (FcRII) on macrophages mediate the endocytosis of antibody-antigen complexes and signal the release of inflammatory and cytotoxic agents. FcRII are also expressed at high levels on B cells where they are less involved in endocytosis than in modulating B-cell activation by membrane immunoglobulins. Although crosslinking of membrane immunoglobulins can result in B-cell differentiation and proliferation through stimulation of phospholipase C, mobilization of intracellular Ca2+, and activation of protein kinase C, crosslinking FcR with membrane immunoglobulins confers a dominant inhibitory signal that prevents or aborts activation. This form of regulation may have a role in the induction of tolerance by IgG and in controlling the B-cell repertoire by anti-idiotypes. The different functions of FcR on B cells and macrophages may reflect the fact that these cell types express closely related but distinct FcR isoforms. We have recently found that the main lymphocyte FcR isoform, FcRII-B1, is unable to mediate endocytosis by way of coated pits and coated vesicles owing to an in-frame insertion of 47 amino acids in its cytoplasmic tail. Here we show that this insert, absent from the FcRII-B2 macrophage isoform, also contains serine phosphorylation sites that may have a role in the ability of FcR to regulate B-cell activation through membrane immunoglobulins. PMID- 2190098 TI - T-cell clones from a type-1 diabetes patient respond to insulin secretory granule proteins. AB - T LYMPHOCYTES reactive to pancreatic beta-cells are thought to have a central role in the autoimmune process leading to type 1 (insulin-dependent) diabetes, but the molecular targets of these T cells have not yet been defined. As identification of such antigens may enable measures to be developed to prevent the disease, we have characterized an antigen that is recognized by insulinoma membrane-reactive T-cell clones established from a newly diagnosed type-1 diabetes patient. Subcellular fractionation studies using rat insulinoma indicate that the antigenic determinant recognized by one of these clones is an integral membrane component of the insulin secretory granule. After a 5,000-fold purification, we have defined the antigen as a monomer of relative molecular mass 38,000. As granular membrane proteins are transiently exposed on the cell surface during exocytosis, their accessibility to components of the immune system may be a function of the secretory activity of beta-cells. PMID- 2190099 TI - Activation of transcription by HIV-1 Tat protein tethered to nascent RNA through another protein. AB - The human immunodeficiency virus type I (HIV-1) nuclear protein Tat is a potent activator of viral gene transcription. Activation by Tat requires a cis-acting element, the transactivation response (TAR) site, located immediately downstream of the transcription start site. Several observations suggest that TAR functions as the nascent RNA product of the HIV long-terminal-repeat promoter (for a review, see ref. 6). Indeed, Tat protein and several cellular proteins bind directly to nascent TAR RNA in vitro. The significance of these in vitro interactions remains to be established. Here we report that Tat can activate transcription when bound to nascent RNA through the RNA-binding domain of another HIV-1 protein, Rev. Rev is a sequence-specific RNA-binding protein, which interacts with the viral RNA element RRE (refs 11-15). A Tat-Rev fusion protein efficiently activates transcription from an HIV-1 promoter derivative, in which TAR has been replaced by the RRE. We conclude that activation of transcription by Tat can occur by direct binding to nascent RNA, and that the sole function of TAR may be to provide a Tat-binding site. Our results further suggest that cellular proteins that bind specifically to TAR RNA or TAR DNA may not be essential for Tat-responsiveness. PMID- 2190101 TI - [The surgical treatment of the Pancoast tumor]. PMID- 2190100 TI - [Ovary hyperstimulation syndrome]. PMID- 2190102 TI - [A central bone bank for bone transplantation]. PMID- 2190103 TI - [Interpretation of gonadotropin determinations; biological versus immunological activity]. PMID- 2190104 TI - [The treatment of dog and cat bites]. PMID- 2190105 TI - Failure of dark adaptation to upregulate D-1 dopamine receptors in retina of senescent rats. AB - The effect of aging on the binding parameters of 3H-SCH 23390, the most selective ligand of D-1 DA receptors, was studied in membrane preparations from the rat retina. DA-stimulated adenylate cyclase activity was also measured in order to better characterize the changes in retinal D-1 DA receptors induced by aging. The binding studies revealed that the density of 3H-SCH 23390 was increased (34 and 73%) in the retina of 14- and 26-month-old rats, when compared to young adult animals, respectively. In contrast, aging failed to alter the sensitivity of the adenylate cyclase to the action of DA. In fact, DA (10(-6) M to 10(-4) M) elicited a similar enhancement in cyclic AMP formation in retinal homogenates of both adult and senescent rats. Since dark adaptation increases the density of D-1 DA receptors in the retina of adult rats we studied the effect of light deprivation on 3H-SCH 23390 binding and DA-sensitive adenylate cyclase activity in the retina of senescent rats. As previously shown (25) light deprivation increased 3H-SCH 23390 binding and enhanced DA-sensitive adenylate cyclase activity in the retina of young adult rats. On the contrary, dark adaptation failed to increase 3H-SCH 23390 binding and to enhance DA-sensitive adenylate cyclase activity in the retina of senescent rats. Taken together these results indicate that D-1 DA receptors in the retina of aged rats have biochemical and functional properties different from those found in the retina of adult animals; these changes may result in an altered response to the physiological stimuli elicited by environmental lighting. PMID- 2190106 TI - Alpha 1-antichymotrypsin is associated solely with amyloid deposits containing the beta-protein. Amyloid and cell localization of alpha 1-antichymotrypsin. AB - Our recent studies demonstrated that alpha 1-antichymotrypsin (ACT), a serine protease inhibitor, was associated with the beta-protein in the brain amyloid deposits of Alzheimer's disease, aged human controls and aged monkeys, suggesting a role for the inhibitor in the amyloid deposition. In the present study we used immunohistochemistry to test for the presence of ACT in the amyloid deposits which contain, as their major component, a protein different from the beta protein. ACT was not found in the amyloid deposits in primary or secondary amyloidosis, familial and amyloidotic polyneuropathy or Creutzfeldt-Jakob disease (non-beta-protein amyloidoses), but was found (together with beta-protein) in Alzheimer's disease, Down's syndrome, normal aging, and hereditary cerebral hemorrhage with amyloidosis of Dutch origin. These results suggest a specific association of ACT with beta-protein amyloid. We next examined the distribution of the inhibitor in normal human brain and in various human neuropathological states in order to identify cells that express this protein during brain degeneration. In addition to its association with amyloid, ACT immunoreactivity was also located in astrocytes near areas of neuronal or tissue loss, in a few neurons and pericytes and in the epithelium of the choroid plexus. PMID- 2190107 TI - [Comparison of echo 2D and echo Doppler in the evaluation of the mitral valve area]. AB - The aim of the study was to compare the degree of accuracy achieved using 2D ultrasonography and Doppler ultrasonography in measuring the mitral valve area. The complementary role of the two methods of diagnosing mitral stenosis and of assessing the severity of valvular involvement emerges from a broad review of the literature. However, in comparison to the two-dimensional technique, Doppler ultrasonography gives a greater mathematical precision and is more reproducible. Doppler ultrasonography enables the pulsatile flow to be registered, while 2D ultrasonography gives a morphological image of the valvular anatomy. "Net" surface values which are closer to real values and usually lower than those obtained using 2D ultrasonography can be deduced from the assessment of the transvalvular pressure gradient. PMID- 2190108 TI - [On lymph node excision in malignant neoplasms of the splenocolic fold]. AB - The latest findings on lymphatic draining of the splenocolic flexure are recalled in a discussion of lymphadenectomy in the surgical treatment of cancer of the left corner of the colon. The main features of the lymphatic down flow ways of this colon segment justify extended exeresis operations as described by Madden and Welti: they also mention colon resection, removal in one block of the spleen and the caudal corporal portion of the pancreas with the lymph node stations of the pancreatico-lienal group invaded by cancer. Some observations are made regarding experience of twenty-five years at various Hospital Surgeries and twenty operated patients: stress is laid on the importance of intraoperative biopsy of the pancreatico-lineal lymph nodes for the purposes of correct staging and for programming extended surgical exeresis. PMID- 2190109 TI - [Etiopathogenetic considerations on local recurrence after excision of rectal carcinoma]. AB - A series of 77 cases of rectum carcinoma observed in a six year period, is presented. Sixty-one patients underwent radical operation and 57 of them have been regularly followed up. The incidence of local relapses has been 12.28%, with a majority of perianastomotic forms. It turned out to be proportional to the aboral distance and to primitive neoplasm staging, but not to histologic differentiation degree. Staplers were used and therefore the choice between resection or amputation was determined by the degree of loco-regional infiltration of the neoplasm. The frequency of local relapses turned out not to be related to the type of operation, but the impossibility to the exeresis of perirectal tissues involved by neoplastic process. PMID- 2190110 TI - [Male varicocele. Analysis of the incidence of varicocele in a population of 18,800 young men]. AB - The authors evaluate the incidence of varicocele after having examined 18,800 healthy white men members of the Italian Army Corps born in 1966 and visited in 1985. They found a varicocele in 775 patients (4.12%), in 5 was present bilaterally, and in 770 in the left side. In 45 patients the surgical treatment was already done at the time of the examination and there were 3 recurrences. The patients with varicocele were divided according to the classification of Dubin Amelar and were: grade I n. 175 (0.93%); grade II n. 515 (2.74%); grade III n. 35 (50.18%). In 566 (73.03%) the diagnosis was done at the moment of the examination, 152 (19.62%) discovered the varicocele at the self examination; in 57 (7.37%) the diagnosis was already done by the family doctor. Infertility is sometime associated to the varicocele and with the unrelieved local discomfort are the main indications for surgery. It should be also emphasized the need of education on the infertility problems during the high school that is a time of the life in which there is the highest incidence of varicocele. PMID- 2190111 TI - [Ileal stenosis caused by chronic granulomatous inflammation secondary to a foreign body simulating Crohn disease]. AB - A case of ileal stenosis due to foreign body induced chronic granulomatous inflammation simulating Crohn's disease with onset on an ileo-ileostomy carried out 23 years before due to iatrogenic rupture of ileal loop following clandestine abortion is reported. After noting the problem of attributing to the foreign body alone responsibility for the stenosis, the hypothesis that it might have been an acute occurrence of Crohn's disease or the expression of an association of Crohn's disease and granulomatous inflammation due to surgical material is advanced. This for the moment is the only plausible cause. It is concluded that for accurate nosological classification and, therefore, definitive clinical diagnosis, prolonged clinical control of the patient is indispensable. PMID- 2190112 TI - Does dietary hyperphagia contradict the lipostatic theory? AB - It has frequently been suggested that body weight or fat somehow exerts an inhibitory influence on food intake in a way that acts to maintain a stable body weight or fat. The principal evidence supporting this idea is that animals that have been induced to overeat and become overweight by various means, eat less than control rats when they are permitted to eat freely. If the degree of suppression of appetite by overweight is as large as several experiments suggest, then dietary hyperphagia should be self-limiting. Any overeating induced by dietary treatments should disappear after animals become moderately overweight. Animals fed some kinds of hyperhagia-promoting diets do show this pattern. However, animals fed other kinds of diets do not show this pattern, and with most diets, dietary hyperphagia continues for extended periods. This implies that either 1) overweight does not suppress appetite as much as suggested by various authorities, 2) dietary manipulations can override normal regulatory mechanisms, or 3) certain diets induce irreversible changes in body fat that are not evident from changes in body weight. PMID- 2190113 TI - The history of benzodiazepine dependence: a review of animal studies. AB - This article provides a historical review of the animal literature relating to the development of tolerance to the behavioral effects of benzodiazepines, and the incidence of biochemical and behavioral changes that result from termination of benzodiazepine treatment (spontaneous withdrawal responses). It charts the slow emergence of a pertinent animal literature and highlights conclusions that were prevalent in 1963 (at the introduction of diazepam), 1973 (at the introduction of lorazepam), 1980 and the present day. For 25 years the animal literature has lagged behind the clinical literature, but recent studies into the neurochemical mechanisms of benzodiazepine dependence and possible treatments for withdrawal responses suggest that, at last, animal experiments may be about to make a substantial contribution. PMID- 2190114 TI - Modes of estrus induction as a factor in studies of the reproductive behavior of rodents. AB - The choice of a mode of estrus for use in studies related to reproductive processes often is made arbitrarily. Females may be in hormone-induced estrus (HIE), cycling estrus (CE), male-induced estrus (MIE), or postpartum estrus (PPE). Although mode of estrus affects various aspects of copulatory behavior in different species in different ways, males mating with PPE females generally require more intromissions to reach ejaculation than with females in HIE or CE; males mating with females in CE generally attain more ejaculations than with PPE females. The duration of receptivity generally is shorter in PPE than in CE. Females in CE and PPE have different stimulus thresholds for pregnancy initiation, with the direction of the difference varying with the species. Among the other phenomena affected by mode of estrus are sperm competition, mate choice, and the Bruce effect. Because mode of estrus can be an important determinant of results, selection of a mode of estrus for any experiment should not be simply a matter of convenience. Further study of effects of mode of estrus is warranted. PMID- 2190115 TI - Neurobiological aspects of the pelvic floor muscles involved in defecation. AB - Neurobiological aspects of the organization of pelvic floor musculature are reviewed. Evolutionary considerations on the origin of these muscles indicate that they develop with specific attachments and function, i.e., do not derive from preexisting muscles such as the ones from the tail. Anatomically, pelvic floor muscles can be divided into 1) true sphincters and related muscles and 2) muscles which flank the visceral outlets. While in quadrupedal mammals the EAS behaves as a fast twitch muscle, in man this muscle has slow twitch characteristics. Like some epaxial muscles the EAS has a strong connectivity with its surrounding skin. In further analogy with some epaxial muscle the EAS, although endowed with muscle spindles, is devoid of the phasic, monosynaptic component of the stretch reflex. Onuf's nucleus which innervates pelvic floor muscles receives an important group of suprasegmental afferents including, probably, direct corticospinal fibers. Pelvic floor muscles play a fundamental role in signaling arrival of feces to the perineum. While sphincteric activity is important for continence, other mechanisms such as the anorectal angle and anal cushions are also of relevance. Although emphasis has been put on motor factors, fecal incontinence can also result from impairments in sensory mechanisms of the anorectal system. In diseases like amyotrophic lateral sclerosis, Werdnig Hoffman's and others there is selective sparing of neuropathology in Onuf's nucleus. In contrast, the nucleus is affected in some autonomic visceromotor neuronal disorders, e.g., Shy Drager syndrome, Fabry's disease. It has been suggested that Onuf's nucleus occupies an intermediate position between visceral and somatic nuclei. PMID- 2190116 TI - Mercury neurotoxicity: mechanisms of blood-brain barrier transport. AB - Mercury exists in a wide variety of physical and chemical states, each of which has unique characteristics of target organ toxicity. The classic symptoms associated with exposure to elemental mercury vapor (Hg0) and methylmercury (CH3Hg+; MeHg) involve the central nervous system (CNS), while the kidney is the target organ for the mono- and divalent salts of mercury (Hg+ and Hg++, respectively). Physical properties and redox potentials determine the qualitative and quantitative differences in toxicity among inorganic mercury compounds, while the ability of MeHg to cross the blood-brain barrier accounts for its accumulation in the CNS and a clinical picture that is dominated by neurological disturbances. This review gives an up-to-date account of mercury's physical and chemical properties and its interaction with biologically active sites pertinent to transport across the blood-brain barrier, a major regulator of the CNS millieu. PMID- 2190117 TI - Introduction--reproductive behavior: a symposium in honor of Frank A. Beach, 1911 1988. AB - A symposium honoring the memory of Frank A. Beach (1911-1988) and celebrating his scientific contributions was held on June 12, 1989 during the 21st Conference on Reproductive Behavior (CRB). The papers arising from the symposium are introduced after a very brief history of the CRB and its origins in an annual meeting of West Coast American sex researchers that was organized by Frank Beach and his colleagues. PMID- 2190118 TI - Multisensory regulation of maternal behavior and masculine sexual behavior: a revised view. AB - Frank Beach's view of the multisensory regulation in Norway rats of copulation in males (12) and of pup retrieval in females (23) is critically analyzed and revised in terms of Lashley's influence, Beach's other work, and current neurobiological knowledge. Beach's view was that no single sensory stimulus is essential to elicit these behaviors, but that all relevant stimuli available summate in the neocortex; consequently, (a) sexual "arousal" is increased in males, leading to copulation, and (b) the "efficiency," or likelihood, of retrieval is increased in postpartum mothers. The revised view is based on a component analysis in which each of these behaviors consists of a chain of motoric responses elicited by somatosensory stimulation. Distal stimuli emanating from the female or pups induce proximity by provoking orientation, attention and arousal; the meaning of these stimuli is largely learned by conditioned associations during the initial executions of the behavior, although odors may have a prepotent influence for some individuals. Stimuli are integrated in a multisensory manner by both subcortical and neocortical mechanisms. Generalizations concerning the reproductive behavior of other mammalian species are suggested. PMID- 2190119 TI - Frank Beach's research on the sexual differentiation of behavior and his struggle with the "organizational" hypothesis. AB - Highlights are described of Frank Beach's research contributions in the area of steroidal control of behavioral sexual differentiation in rats and beagle dogs. Beach's initial struggle with and his subsequent partial acceptance of the organizational hypothesis of steroidal action in the developing male nervous system as an explanation of these steroidal effects on behavior, advanced by W. C. Young and co-workers, is also chronicled. PMID- 2190120 TI - Forebrain influences on brainstem and spinal mechanisms of copulatory behavior: a current perspective on Frank Beach's contribution. AB - In a 1967 Physiological Reviews paper, Frank Beach put forth four propositions regarding forebrain and hormonal control of brainstem-spinal mechanisms of copulatory behavior. Simply stated, he proposed that: 1) the forebrain exerted an inhibitory control over species-typical copulatory reflexes through descending effects on brainstem-spinal mechanisms and 2) gonadal hormones influence these reflexes largely by actions on forebrain control processes rather than by direct effects on the brainstem or spinal cord. This theoretical scheme was of great heuristic significance during the subsequent two decades of research, which has largely supported and delineated in greater mechanistic detail the processes Beach hypothesized to exist. This subsequent research has also shown the central nervous system actions of gonadal hormones to be more widespread and complex than Beach proposed. Some of these recent research findings are presented, with emphasis on neurophysiological studies which have identified hormone-induced functional changes in forebrain and brainstem neurons. It is proposed that these functional changes may represent a mechanism for the behavior-controlling actions of hormones that were hypothesized by Beach. PMID- 2190121 TI - Sexual motivation: a neural and behavioural analysis of the mechanisms underlying appetitive and copulatory responses of male rats. AB - Experiments investigating the neural mechanisms underlying the expression of masculine sexual behaviour are discussed in the context of the hypothesis set out by Frank Beach that suggested the existence of separate sexual arousal and performance mechanisms. The results indicate that the medial preoptic area is crucially involved in consummatory aspects of sexual behaviour: lesions and chemical manipulations of the area profoundly affect mounts, intromissions and ejaculation, but tend not to alter appetitive sexual responses. By contrast, ventral striatal dopamine-dependent mechanisms primarily affect appetitive sexual responses, measured in a variety of paradigms, but tend not to alter copulatory behaviour itself. Finally, associative mechanisms, for example those by which arbitrary environmental stimuli come to control appetitive sexual responses through their predictive association with sexual reinforcement, are shown to depend at least in part on interactions between the basolateral amygdala and dopamine-dependent events in the ventral striatum. Thus, diverse neural and behavioural procedures have revealed that separable neural mechanisms appear to be involved more or less selectively with different components of the male rat's sexual response system. It may still be useful to conceptualize separate sexual arousal and intromission/ejaculatory mechanisms when studying the neuroendocrine basis of sexual behaviour. However, a major challenge is to understand the way in which elements of the telencephalic limbic system, the striatum and preoptic area, some of which are targets for the action of sex steroids, interact to produce an integrated pattern of sexual behaviour. PMID- 2190122 TI - Desire and ability: hormones and the regulation of female sexual behavior. AB - The distinction between the ability to copulate and the desire to copulate is used to understand species differences in hormonal regulation of female sexual behavior. Evidence is presented demonstrating that ovarian hormones modulate female sexual motivation in both rodent and primate females. The thesis is developed that rodent females differ from primate females primarily in their dependence upon hormones for the ability to mate. Thus, apparent differences between the two groups of females in the extent to which hormones control copulatory behavior does not stem from differences in hormonal regulation of female sexual motivation but from the physical ability of primate, but not rodent, females to mate without hormonal stimulation. This emancipation of the ability to copulate from hormonal influence makes female sexual motivation the primary regulator of mating in primates. Dependence upon female sexual motivation means that the copulatory behavior of primate females is easily influenced by their physical and social environment. Because primate females can mate without hormonal input, female sexual initiation, not copulation, is argued to be the only valid indicator of female sexual motivation. PMID- 2190123 TI - Is the snark still a boojum? The comparative approach to reproductive behavior. AB - One of Frank Beach's many achievements was his stimulating influence on the comparative study of behavior. This review honors that legacy by categorizing and describing the many kinds of comparative approaches in use today for the study of reproductive behavior. The categorization is based on the motives and goals of the researcher, the kinds of questions that can be answered, the number and phylogenetic relatedness of the species being compared, and the method used for analyzing the results. Each approach is illustrated with specific examples from recent research, using studies from the field of hormones and behavior whenever possible. PMID- 2190124 TI - Current trends in routine newborn male circumcision in New York State. AB - Despite the fact that circumcision of the new-born male has been practiced for at least 6,000 years, the procedure remains controversial. Circumcision rates in the United States remain among the highest of any nation in the industrialized world, yet there is little descriptive data on the demographic characteristics of newborns who are circumcised. New York State's hospital discharge data were used to examine demographic patterns for the procedure for the period 1980-1986. Circumcision was less common in New York City than in other areas of New York State, and was more common in private hospitals than in public hospitals. Whites had the highest rate of circumcision (70%), while Hispanics had the lowest (25%). Newborns under Medicaid coverage were more likely to be circumcised in voluntary hospitals than in public hospitals (45% vs 33%). We conclude that circumcision rates vary depending on a variety of factors, some of which may be attributable to the physician and others to family and society. PMID- 2190125 TI - Diphtheria and medical therapy in late 19th century New York City. PMID- 2190126 TI - Salmonella arthritis. PMID- 2190127 TI - The use of a Swan-Ganz catheter and streptokinase in the management of massive hemoptysis. PMID- 2190128 TI - Ovarian remnant syndrome: difficulties in diagnosis and management. AB - Ovarian remnant syndrome should be considered in the differential diagnosis of pelvic pain with a mass in a patient who has had extirpative surgery. Although rarely reported in the literature, it is probably much more prevalent than is suspected. Most commonly, the initial surgery was performed for endometriosis or pelvic inflammatory disease, with incomplete excision of the ovaries. Surgical excision of the ovarian remnant, the definitive treatment, is itself difficult, and is often attended by serious complications. Medical therapy is empiric, and hormonal manipulation may help prevent recrudescence. Three cases are reported, their pathology and the literature is reviewed. PMID- 2190129 TI - Intracranial hemorrhage during pregnancy and puerperium. AB - Intracranial hemorrhage during pregnancy is very rare. This catastrophic event has a poor prognosis and can contribute to maternal death for nonobstetrical reasons. The proper management during pregnancy remains controversial. Increasing awareness of the condition had been prompted by the fact that an acquired diagnosis is now usually available and a definitive and successful surgical procedure may be possible. PMID- 2190130 TI - A longitudinal study comparing growth in diabetic pregnancies with growth in normal gestations: I. The fetal weight. AB - Diabetes mellitus is associated with fetal growth acceleration and retardation. These aberrations in fetal growth seem to be influenced by a variety of factors including vascular disease, glycemic control, hypertension and smoking. In order to characterize fetal growth under the above conditions, longitudinal sonographic evaluations were performed in 52 pregnant, insulin-dependent diabetic women with the usual monitoring of the patients' metabolic control. Regression analyses revealed that vascular disease and glycemic conditions were the most important influences for growth, with manifestation beyond the second trimester. With stringent glucose control (mean whole blood less than or equal to 100 mg/dl) in the absence of vasculopathy (white classes A, B, C), fetal growth was similar to that in normal pregnancies. In the presence of vasculopathy (white classes D and FR), growth was reduced, especially when near-normal glycemic levels were achieved. Conversely, in poorly controlled diabetic women, enhanced fetal growth were observed in patients with and without vasculopathy. No aberrations in fetal growth were observed, however, before the third trimester. The findings of our study demonstrate that vasculopathy and glycemia are dominant and independent regulators of fetal growth. However, their influences are not manifested in growth changes before the third trimester. PMID- 2190131 TI - Transcervical division of uterine septa. PMID- 2190132 TI - A modified iris fixation suture utilizing a peripheral iridectomy. AB - To help ensure proper placement of an iris fixation suture, a peripheral iridectomy can be performed to allow visualization of the superior haptic of a posterior chamber intraocular lens (PC-IOL). In cases where support for the PC IOL is in question, an iris fixation suture using this technique provides an easy way of ensuring adequate support. PMID- 2190133 TI - Eye movement disorders in men with isolated hypogonadotropic hypogonadism. AB - The eye movement abnormalities in two men with isolated hypogonadotropic hypogonadism were studied clinically and electro-oculographically. Both demonstrated striking saccadic dysmetria. Subsequent neuroradiologic investigation confirmed atrophy of the cerebellar vermis in one of the patients. This is in concert with other midline structural abnormalities described in patients with isolated hypogonadotropic hypogonadism and suggests that this syndrome may arise from a genetically linked developmental abnormality of midline central nervous system structures. PMID- 2190135 TI - Usher's syndrome. AB - Usher's syndrome is an autosomal recessive condition of congenital sensorineural hearing loss and retinitis pigmentosa. Other abnormalities are present but inconsistently, suggesting the genetic concepts of pleiotropy and heterogeneity. Accordingly, several classifications have been suggested. Clinical findings involve the visual, auditory and vestibular systems. The identification of the carrier state would allow for more timely and accurate genetic counselling. A screening program for Usher's syndrome appears feasible. This would allow affected, deaf individuals to prepare themselves for the expected visual loss giving them a better chance for a productive, fulfilling life. PMID- 2190134 TI - Best's vitelliform dystrophy. AB - Best's vitelliform dystrophy is an autosomal dominant disease that pathologically affects the retinal pigment epithelium and symmetrically affects the macula of patients at a very young age. Visual acuity tends to remain quite good for long periods of time. In the later stages of the disease, atrophic changes of the retinal pigment epithelium or scarring secondary to subretinal neovascular membranes with hemorrhage may cause a loss of central visual acuity. An abnormal diminished light to dark ratio of the electrooculogram is the hallmark of the disease. No other significant ocular abnormalities or systemic problems have been associated with this genetic disorder. No therapy exists for halting the progression of the disease with the possible exception of laser photocoagulation treatment used to ablate subretinal neovascular membranes in an attempt to avoid complications of subretinal hemorrhages. However, an accurate diagnosis and pedigree analysis is important for allowing the physician to perform adequate family and genetic counseling to affected patients. PMID- 2190136 TI - [Methods of autodermatoplasty in injuries of the extremities]. AB - The authors have proposed a method of fixation of an autodermal graft by using a net sewn to the healthy skin areas with single knot sutures and a method of autodermatoplasty of extensive defects of the soft tissues of the extremities. These methods have been successfully used in 29 patients. There have been no complications. PMID- 2190137 TI - [A method of temporary percutaneous ligation of major blood vessels of the extremities]. PMID- 2190138 TI - Routine immunizations for American children in the 1990s. AB - It has been suggested that one of the major advances in medicine, and for society at large, has been the development of vaccines and the adoption of routine immunization by the vast majority of responsible health care practitioners in the developed nations. Thankfully, there continue to be rapid advances in our ability to diagnose and treat infectious diseases. However, with these rapid advances come necessary changes in the dogma of medical practice, including changes in the routine immunization procedures recommended by various authoritative bodies in the United States. New immunizing agents will be developed and will achieve routine use. Unexpected adverse reactions and complications of our immunization reagents must constantly be sought and described. Previously unrecognized subgroups of hosts at special susceptibility to adverse and untoward vaccine effects will be recognized; the pathogenesis of their special susceptibility needs to be understood and then will have to be appropriately addressed. Individual health care practitioners will need to keep abreast of routine immunization recommendations and the application of these recommendations in an organized and thorough fashion to infants, children, adolescents, and adults. A crucial link in the chain of optimal preventive health care will continue to involve those who prescribe, order, and administer vaccines. PMID- 2190139 TI - Pertussis vaccines. AB - Concern over adverse reactions temporally associated with whole cell pertussis vaccine and advances in the understanding of the Bordetella pertussis organism have led to a new generation of more purified acellular vaccines. The biology of the pertussis organism, epidemiology of disease, vaccine development over the decades, and vaccine efficacy and adverse reaction data from whole cell and acellular vaccine trials are presented. Questions that remain to be answered before acellular vaccine replaces conventional vaccine are defined, and future studies addressing these questions are proposed. PMID- 2190140 TI - New vaccines against Haemophilus influenzae type b. AB - Recently, great progress has been made in the development of vaccines against Hib. Four polysaccharide-protein conjugate vaccines are actively being tested. Three of these (PRP-D, HbOC, and PRP-OMP) are currently licensed for use in children at 15-18 months of age. Clinical trials of these vaccines in infants are currently being conducted in the United States. If these show the vaccines to be efficacious, licensure for infants will follow. Although much work remains to be done, it seems likely that the effective prevention of serious Hib infections in infants, as well as in older children, is a goal that may be within our reach in the next several years. PMID- 2190141 TI - Measles vaccines. AB - Measles vaccine is one of the safest and most effective vaccines currently available. Use of the vaccine has decreased the incidence of measles in both developed and developing countries. Nevertheless, preventable morbidity and mortality continue to occur. In the United States, the measles problem differs when it occurs among preschool-aged children or school-aged children. The former is a due to insufficient vaccine delivery. For measles in school-aged and college students, the problem is primarily vaccine failure, which should eventually be solved by a two-dose schedule. In developing countries, the major problem is vaccine delivery. Use of Edmonston-Zagreb measles vaccine in developing countries offers the promise of reducing disease rates in young infants; however, in both the United States and in developing countries, increasing immunization levels is essential. PMID- 2190142 TI - Rubella and mumps vaccines. AB - As a fetal infection occurring during early pregnancy, rubella's potential for teratogenicity is unparalleled. In the postnatal period it is a relatively benign disease. Mumps, on the other hand, causes moderate morbidity and occasional mortality. Both infections cause considerable morbidity and disruption in the lives of young people gathered for group activities. Widespread use of safe and effective live attenuated vaccines has dramatically reduced the incidence of rubella, congenital rubella, and mumps in the United States. Nevertheless, significant numbers of young children, especially in areas of urban and rural immigration and poverty, fail to be immunized in a timely fashion; and some adolescents and young adults remain susceptible either because they escaped immunization in childhood or are primary vaccine failures. These individuals remain the source of individual cases and small outbreaks of rubella and mumps. For total eradication of these infections, we need to intensify vaccine efforts and to maintain surveillance efforts for mumps, rubella, and congenital rubella syndrome. PMID- 2190143 TI - Influenza: status and prospects for its prevention, therapy, and control. AB - This article describes current knowledge of the molecular properties of orthomyxoviruses, their epidemiology, and approaches to the control of influenza. The host's response to infection, approaches to prevent infection through vaccination, and the use of antiviral agents to treat or prevent this important infection are covered. PMID- 2190144 TI - Surveillance. Information for action. AB - Success in immunization requires success in developing an adequate information base. While special studies are important, there is no substitute for surveillance systems. Such systems help evaluate health impact, monitor trends in reported disease and adverse events, and identify areas for more intense investigation. Surveillance data alone have played major roles in immunization strategy changes. Successful surveillance relies on cooperation by health care providers and health departments. While filling out forms and reporting cases may be viewed as a burden by some, such information in the aggregate becomes an important part of the knowledge base used to refocus implementation efforts and potentially to change strategies. Reporting by all physicians is particularly important when reported cases lead to aggressive control actions such as outbreak control. Rapid reporting even when cases are not confirmed can help health departments ensure that needed laboratory specimens are collected and allow control measures to be undertaken before disease containment becomes difficult. In conclusion, any immunization program worth instituting is worth monitoring. Surveillance represents constant vigilance to ensure effective control or elimination of disease. PMID- 2190145 TI - Vaccine-preventable disease and immunization in the developing world. AB - Vaccines have given health care providers control over a substantial portion of the morbidity and mortality in the developing world. Global efforts have immunized two-thirds of the world's children with DTP and polio vaccines; 72% have received BCG and 59% measles vaccine; but only 29% of pregnant women have received two doses of tetanus toxoid. In addition, vaccines against yellow fever, Japanese encephalitis, hepatitis B, rubella, and mumps and meningococcal polysaccharide vaccine are being used in specific regions of the world. New vaccine candidates will enhance the vaccine armamentarium over the next decade to include the causes of pneumonia, diarrhea, and meningitis: Haemophilus influenzae type b, pneumococcal and meningococcal protein conjugate vaccines, typhoid and rotavirus vaccine. Genetically engineered vaccine vehicles, genetic reassortants, and genetic deletions are being investigated as new vaccine candidates. PMID- 2190146 TI - Vaccines for foreign travel. AB - Exotic infections are a significant threat to the child traveling to or going to live in the developing world. Vaccines are available that can prevent some of these infections. It is essential that basic routine childhood vaccination be up to date and that necessary modifications be made from the usual schedule in the United States. The current requirements and local disease conditions (both endemic and epidemic) for each country to be visited must be known so that appropriate vaccines are received. Resources for this information are listed. Details for each vaccine are given, including indications, dose, booster, side effects, contraindications, and other specific information. PMID- 2190147 TI - Medical-legal aspects of immunization. Policy and practices. AB - The experience in the United States with the vaccine liability crisis demonstrates the vulnerability of public health policy and practice standards to independent developments in the legal arena. Scientific progress in the fields of immunology and molecular biology offer promise for the control of an increasing number of communicable diseases through immunization. Legal protections for pharmaceutical laboratories, manufacturers, and providers are appropriate incentives to continued development, supply, and administration of effective, affordable vaccines. At the same time, potential recourse to litigation in the courts in the event of vaccine-related injury provides society with desirable assurances of enforceable industrial and professional standards, as well as financial support for those who sustain serious adverse reactions to licensed vaccines. The National Childhood Vaccine Injury Act of 1986 is an attempt to construct an equitable solution to this dilemma. Interested physicians and lawyers will have a role to play in the search for an appropriate balance between these important but competing values. Progress in science and the law in the field of public health generally, and vaccine development specifically, should be a collaborative enterprise. Familiarity with, and respect for, the basic principles and theories of both fields will be essential to this endeavor. PMID- 2190148 TI - Lung disease in cystic fibrosis--an updated concept. PMID- 2190149 TI - The echogenic ependymal wall in intraventricular hemorrhage: sonographic pathologic correlation. AB - Fifty-one patients with ultrasound diagnosis of intraventricular hemorrhage (Grades III and IV) were studied retrospectively for the presence of ependymal echogenicity. The sonographic findings were then correlated with histologic findings in six autopsy cases. Forty-one out of fifty-one newborns with intraventricular hemorrhage developed ependymal echogenicity on serial ultrasound studies. This echogenicity appeared approximately seven days after the hemorrhagic event and usually disappeared in about six weeks. Histologic examination revealed disruptions in the ependyma with proliferation and extension of subependymal glial cells onto the ventricular surface in those cases in which ependymal echogenicity was present at the time of death. This layer of proliferating subependymal glial cells may account for the ependymal echogenicity. PMID- 2190150 TI - Major pitfalls in Doppler investigations. Part II. Low flow velocities and colour Doppler applications. AB - Many pitfalls result from the limited ability of Doppler instruments to record low flow velocities. These include a misleading resistance or pulsatility index due to diastolic cut-off and taking no signal to equal no flow assuming that no signal means no flow. Comparison of actual flow velocities as measured in an in vitro system (range: 0.8 to 3.4 cm/s) with the lowest recordable spectral or colour signals in 3 Duplexscanners showed that reduced sensitivity to low flow velocities is not only dependent on the high pass ("wall") filter setting, Doppler frequency or angle of incidence, but also on factors such as vessel diameter, impairing the signal to noise ratio. Characteristic errors of colour flow mapping (misleading vascular anatomy, imitation of pathological findings, erroneous exclusion of flow) are due to partial volume effect, limited temporal and velocity resolution, changing angle of incidence, aliasing and failure to detect low flow velocities. PMID- 2190151 TI - Unsuspected hepatic injury in the neonate--diagnosis by ultrasonography. AB - Three cases of severe neonatal hepatic injury were investigated with ultrasonography. The injury is often associated with antenatal factors (fetal hepatic enlargement, maternal trauma), perinatal factors (breech presentation, pre- or post-maturity, difficult delivery), or postnatal factors (resuscitation). PMID- 2190153 TI - Enteric duplication cysts in children: are their ultrasonographic wall characteristics diagnostic? AB - We reviewed eight cases of gastrointestinal duplication cysts to determine whether the combination of an echogenic inner mucosal layer and hypoechoic outer muscular layer could be seen consistently enough to be of diagnostic value. We compared our findings to those seen in twenty-seven other abdominal cysts and conclude that when identified together, the two layers are highly suggestive, if not completely diagnostic of enteric duplication cysts. PMID- 2190152 TI - Pancreatic echogenicity in premature and newborn infants. AB - Little information is available regarding pancreatic echogenicity in premature infants and neonates. We prospectively studied 65 patients (30 premature infants and 35 neonates) and compared pancreatic echogenicity to a control group of 25 infants and 35 older children. Pancreatic echogenicity was graded relative to hepatic echogenicity measured at a similar depth. In the premature infants and neonates the initial ultrasounds were hyperechoic in 71% compared to 5% in both control groups. Follow up ultrasounds were obtained in 73% of the premature infants and 17% of the neonates. The pancreatic echogenicity became isoechoic in 14 of 19 premature infants and 3 of 4 neonates in whom the initial ultrasound was hyperechoic. We conclude that the normal pancreatic echogenicity in premature infants and neonates is usually hyperechoic relative to liver. Pancreatic hyperechogenicity in premature infants and neonates is not necessarily indicative of disease. PMID- 2190154 TI - Testicular infarction in the newborn: ultrasound findings. AB - Three patients with neonatal testicular torsion and infarction (two bilateral, one unilateral) are presented with a distinctive sonographic appearance. All five testes appeared inhomogeneously hypoechoic and each was surrounded by a brightly echogenic rim. Whereas surgical exploration was required in the past to establish the diagnosis of testicular infarction in the neonate, sonographic demonstration of the abnormality in the appearance of the testicular parenchyma permits nonoperative diagnosis. Because surgical salvage of the testis in the setting of neonatal extravaginal torsion is thought to be quite rare, the necessity of removing the testis is less clear when the diagnosis is established preoperatively. PMID- 2190155 TI - Ultrasonography of the hip in preterm neonates. AB - Over the period of one year, the hips of 92 preterm neonates were examined by ultrasound. Using the Graf classification only 7% showed an angle alpha between 50 and 60 degrees, which is characteristic of type IIa hips. In all other cases the angle alpha was above 60 degrees (type I). Sonographically there were no pathological cases (type IIg or worse). A reason for the relatively low number of type IIa hips could be that the short osseous acetabular rim and the broad cartilagenous Y-joint in this age group result in a "false" increase of the angle alpha. PMID- 2190156 TI - Milk of calcium fluid collection in dermatomyositis: ultrasound findings. AB - Extensive subcutaneous and intermuscular calcium laden fluid collections (milk of calcium) were found in two young girls with severe dermatomyositis. Sonographic examination clearly showed the nature and extent of the collections. Knowledge of this new feature of dermatomyositis should help avoid confusing these fluid collections with soft tissue infection and deep abscess in these often steroid dependent children. PMID- 2190157 TI - Ultrasound in intussusception: a false cystic lead point. AB - Lead point lesions are very rarely suspected during ultrasound (US) investigation of intussusception. We report a case of idiopathic intussusception where US suggested a cystic lead point. At operation there was no structural abnormality but fluid was noted to be trapped within intussuscepted mesentery. The incidence of 'non-idiopathic' or 'secondary' intussusception is 5-6% with Meckles diverticulum being numerically the most important single entity. The lead point is only rarely identified on ultrasound. A large Chinese series of 377 cases of diagnosis and reduction of paediatric intussusception under US control [1] makes no mention of ultrasonic identification of a secondary cause in any of their cases. A European series of 145 cases [2] noted a causative lesion in 8 (5.6%), of which 2 (lymphoma, intestinal duplication) were identified during the ultrasound study. Adamsbaum [3] recently published a case of an enterogenous cyst as a lead point identified on ultrasound. We present a case with very similar ultrasonic features but which at operation was found to represent fluid trapped within the intussuscepted mesentery rather than a true cystic lead point. PMID- 2190158 TI - Pulmonary arteriovenous fistula: ultrasonographic approach. AB - Report of a pediatric case with pulmonary arteriovenous fistula (PAVF) in hereditary hemorrhagic teleangiectasia (HHT), primary suspected by ultrasound. There is a characteristic sonographic feature of the complex type of PAVF revealing septations in contrast of the simple type. The diagnosis was established by angiography. PMID- 2190159 TI - Parotid gland abnormality found in children seropositive for the human immunodeficiency virus (HIV). AB - Out of our series of 24 children seropositive for the Human Immunodeficiency Virus (HIV), parotid gland enlargement was noted in 4 children with AIDS-related complex (ARC) presenting also a Lymphocytic Interstitial Pneumonitis (LIP) on their chest radiographs. The ultrasound (US) aspect of the parotid gland suggests acinar enlargement (suggesting the presence of lymphocytic infiltration). The aspect displayed in the parotid mirrors the process developing in other areas (lungs, liver, spleen, lymph-nodes), i.e. a syndrome of lymphocytic (CD8) proliferation present at the stage of ARC. PMID- 2190160 TI - Documentation of spontaneous reduction of childhood intussusception by ultrasound. AB - Spontaneous reduction of a presumed ileo-colonic intussusception was demonstrated by ultrasound examination followed by a barium enema. No premedication or anesthetic had been given to the child. This case illustrates the possible natural history of intussusception rarely confirmed by imaging studies. Intussusception is the most common abdominal emergency of early childhood. Diagnosis and therapy is usually performed with a contrast enema. If unsuccessful, surgical reduction is indicated. We wish to report a case of spontaneous reduction of a presumed ileocolonic intussusception. This was initially diagnosed by ultrasound examination, but had spontaneously reduced by the time a barium enema was performed. PMID- 2190161 TI - Intrahepatic encystment of umbilical vein catheter infusate. AB - Massive hepatomegaly in a 2.1 kg female infant, with an indwelling umbilical vein catheter for total parenteral nutrition, occurred on the 10th day of life. Ultrasound and computed tomography studies revealed a large hepatic cyst filled with the catheter infusate. Percutaneous drainage brought about subsequent recovery. To our knowledge, this complication of umbilical vein catheter use has not been previously reported. PMID- 2190162 TI - Fetal hydrocele: a persistent finding? AB - A transient type of fetal hydrocele is described. This type of hydrocele resolves in utero spontaneously and may be a variant of normal testicular development. PMID- 2190163 TI - Transient acute tubular dysfunction in the newborn: CT findings. AB - We report the CT and sonographic findings of transient acute tubular disease in a newborn infant, who was dehydrated at birth. The initial CT scan demonstrated focal areas of increased attenuation within the central portions of both kidneys, and sonography showed echogenic medullary pyramids. After adequate hydration, a follow-up examination demonstrated complete spontaneous resolution. PMID- 2190164 TI - Stippled epiphyses in fetal alcohol syndrome. AB - We report on punctate epiphyseal calcifications (stippled epiphyses) in the fetal alcohol syndrome and present the differential diagnosis of chondrodysplasia punctata. A literature survey shows that epiphyseal calcifications accompanying alcoholic embryopathy are regularly located in the lower limbs and rarely found in the upper extremities. PMID- 2190165 TI - [Experience with the use of a new autonomic drug butyroxan in patients with gastroduodenal pathology and autonomic dysfunction]. PMID- 2190166 TI - [Comparative effectiveness of the use of enterodes in acute allergic syndromes in children]. PMID- 2190167 TI - [Urinary microflora and the status of local immunity in children with cystitis]. AB - Study of the enzymatic and adhesive properties of E. coli isolated from the urine of children with cystitis has demonstrated that P-fimbriae, DNAase- and phosphatase-positive strains with pronounced hemolyzing and metabolic properties mostly occurred in children with associated cystitis and chronic obstructive pyelonephritis. In children suffering from cystitis, the changes on the part of local immunity manifested by the decrease of the content of SIgG in the urine and by the lack of SIgA1 and SIgA2. In children with a disease standing up to 3 years, the synthesis of IgA turned out dominant in the mucous membrane of the neck of the urinary bladder and in the trigone of the bladder, with IgG and IgM output being less intensive. The authors have proved the efficacy of the treatment with tomicide instilled into the urinary bladder of children suffering from cystitis. PMID- 2190169 TI - [Diagnostic value of renal echography in children]. AB - Echography was employed to examine 94 children with different renal pathology. 45 children had chronic secondary pyelonephritis in the presence of the vesicoureteral reflux, 18 hydronephrosis, 14 ureterohydronephrosis, 6 chronic non obstructive pyelonephritis, 5 acute glomerulonephritis, and 6 chronic glomerulonephritis. The data obtained by ultrasonography and x-ray data were studied and compared. The results thus derived supplement and make it possible to review the former ultrasonic criteria for normal and pathological conditions with unmarked morphological alterations in the kidneys. Novel criteria for the size of the lumen of the collecting systems are presented. PMID- 2190168 TI - [Structural and functional status of the kidneys in children with nephropathies associated with metabolic disorders]. AB - A total of 365 children aged 1 to 16 years were examined. The dimensions of the kidneys are given in health and in nephropathies associated with metabolic disorders. Echography made it possible to identify the presence of salt crystals in the pelves. The tension of osmoregulating renal function in response to water loading manifested by the reduction of the degree of osmotic dilution and the rise of ion excretion was established. One of the reasons for such alterations is plasma hyperosmia that is likely to be conditioned by the rise of salt concentrations in the blood. The functional changes seen in the kidneys were found to depend on the age. PMID- 2190170 TI - [Echographic measurement of the size of the kidneys in premature newborn infants]. PMID- 2190171 TI - [Clinico-immunologic indicators in children with opisthorchiasis in relation to the use of various anthelmintics]. PMID- 2190172 TI - [Clinical effectiveness of the use of vitamin E and essential in the treatment of Salmonella infection in children]. PMID- 2190173 TI - [Venous thromboembolism. "The emperor's new clothes" or a silent menace?]. AB - The clinical picture at deep venous thrombosis and lung embolism is unspecific and the diagnosis is confirmed in only about 50 per cent of the patients by phlebography and lung angiography respectively. New contrast media have reduced the side-effects at phlebography. Of the non-invasive methods B mode ultrasound is a rapid, simple procedure with great diagnostic accuracy but lower leg thromboses cannot be demonstrated with the present equipment. High diagnostic accuracy has been attained at lung embolism by means of perfusion ventilation scintigraphy and lung angiography. ECG, acid-base status and thorax X-ray provide guidance and are of major significance for differential diagnosis. All cases of deep venous thrombosis above knee level should be treated with anticoagulants but such therapy is probably unnecessary for lower leg thromboses. Heparin is frequently given for three to six days. At the same time peroral anticoagulation therapy may be introduced and continue for one to three months after heparin treatment. Lung embolism is treated with anticoagulants if the patients are hemodynamically stable. The value of thrombolysis has not been determined but it is recommended for massive multiple and peripheral lung embolisms. Embolectomy should be considered in cases of massive central lung embolisms. PMID- 2190174 TI - Kikuchi's histiocytic necrotizing lymphadenitis. AB - Histiocytic necrotizing lymphadenitis (HNL) or Kikuchi's Disease is a peculiar condition most commonly affecting cervical lymph nodes in young women. Histology and immunohistochemistry demonstrate a florid T-cell and histiocytic reaction associated with necrotic areas which must be carefully distinguished from malignant lymphoma. Usually, the disease resolves spontaneously within a few weeks or months. The etiology is unknown and the physiopathology discussed. PMID- 2190175 TI - Detection of minimal residual disease in leukemias: a critical approach. AB - The detection of minimal residual disease (MRD) represents a major goal in leukemias with great potential applications: identification of patients at high risk of relapse, earlier detection of relapses, possible improvement of autologous bone marrow transplantation (determination of the best time for bone marrow harvest and assessment of its quality). Theoretical requirements for a model of MRD detection exist and are recalled. Numerous methods (cytology, immunology, cytogenetics, clonogenic assays, molecular biology) have been used. All share limitations which may concern sensitivity, specificity, reproducibility, conveniency. Progresses will be brought by more sophisticated methods in immunology (double staining with or without flow cytometry) and above all molecular biology (revolutioned by polymerase chain reaction applications). PMID- 2190176 TI - The physiology and biochemistry of retinoic acid. AB - The ability of the fat soluble Vitamin A to modulate cellular differentiation has been known for over 60 years. Numerous studies have shown that Vitamin A and its 2 major metabolites play a key role in vision (retinal) and cell differentiation (retinoic acid, RA). The control of cellular differentiation may be exercised on a variety of tissues including simple and stratified epithelia, the latter will be the focal point of this article, with emphasis being given to the skin. In the development of the limb bud, RA has been proposed as a morphogen controlling development via a concentration gradient established by a mechanism thought to involve specific nuclear receptors and a cytosolic binding protein (CRABP). In the hemopoietic system, RA is known to modulate several functions of polymorphonuclear leucocytes (PMN) in vitro and the differentiation of granulocyte macrophage-precursors. Moreover it has been shown to exert immunomodulatory properties. PMID- 2190177 TI - In vitro effects of retinoic acid. AB - Retinoids, synthetic and natural analogues of vitamin A, play fundamental roles both in directing the spatial organization of cells during the development of vertebrate limbs and in the maintenance of growth and differentiation of many adult tissues. They also block the phenotypic expression of cancer in vitro; inhibit growth and induce differentiation in many animal and human malignant cell types. They have proved beneficial in skin diseases, cancer prevention and in acute promyelocytic leukemia. PMID- 2190178 TI - Retinoic acids in the treatment of acute promyelocytic leukemia. AB - Retinoic acid, the active metabolite of vitamin A has been shown to differentiate in vitro human leukaemic cells from patients with acute promyeolocytic leukaemia (APL). The results obtained in vivo with the 13-cis isomer of retinoic acid in combination with or after chemotherapy in four cases of APL are described. More recently Huang et al from the Shangai Institute of Haematology have treated 24 cases of APL with all-trans retinoic acid alone. They obtained 24 complete remissions. This success prompted us to treat patients with APL and a contra indication to chemotherapy with all-trans retinoic acid. The results confirm the great efficacy of all-trans retinoic acid in APL. PMID- 2190179 TI - T cell adhesion. AB - Antigen recognition by the T cell receptor cannot ensure by its own T cell activation. Other membranes molecules are required in order to achieve transient but strong adhesion of the T cell to the antigen presenting cell. Two main molecular adhesion pathways have been characterized involving the CD2 molecule binding the LFA-3 molecule and the LFA-1 molecule binding the ICAM-1 or ICAM-2 molecule. These results have been provided by the use of the three approaches, i e inhibition of T cell activation and adhesion by monoclonal antibodies, the study of the adhesion of lymphocytes that do not express one or several adhesion molecules and finally the demonstration that the transfection of gene(s) coding for adhesion molecules into fibroblasts cotransfected with HLA molecules make the latter cells able to present antigen(s). The importance of the concept of antigen independent T cell adhesion has been further underlined by in vivo use of monoclonal antibodies specific for adhesion molecule(s): LFA-1. Such antibody can efficiently block rejection of HLA non identical bone marrow in children. This opens further prospect of immunosuppression through blocking of T cell adhesion. PMID- 2190180 TI - Autologous bone marrow transplantation in Hodgkin's disease. AB - The outcome of advanced Hodgkin's disease has improved since the use of MOPP and ABVD. However 50% of these patients will relapse. Conventional salvage therapy can yield a complete response rate of 50%. However, only 5 to 30 percent can expect to be cured. Autologous bone marrow (ABMT) in reported publications can reach 50 to 80% remission rate in refractory patients with a disease free survival of 40 to 80%. Adverse prognostic factors are: tumor burden, number of prior chemotherapies, response to latest therapy and performance status. At the present time, ABMT is discussed in relapse of poor prognosis with initially stage I to IIIA. Twenty-six patients underwent ABMT at Saint-Louis Hospital. Fifteen were sensitive relapses of poor prognosis, 11 initially refractory disease. After ABMT, 19 were in complete remission including 14 relapses. Disease free survival was 80% for relapsing patients, again 50% for refractory patients (P = 0.001). ABMT should be a tool for refractory patients and relapses of poor prognosis. PMID- 2190181 TI - Recent developments in the diagnosis of the hemoglobin disorders. PMID- 2190182 TI - The Philadelphia translocation in CML and ALL: recent investigations, new detection methods. AB - As a consequence of the Ph translocation, a bcr-abl fusion gene is formed that encodes chimeric bcr-abl proteins. The latter are probably causally involved in leukemogenesis, although the mechanism is not yet known. Meanwhile, the heterogeneous aspects of the Ph translocation have been explored in an effort to disclose their eventual clinical significance. Innovative and useful methods have been devised for the detection of the Ph translocation products e.g. the PCR technique or the production of specific antibodies that undoubtedly will prove to be of great help to patients and clinicians in future. PMID- 2190183 TI - The effect of context on synonymous codon usage in genes with low codon usage bias. AB - The effect of neighbouring bases on the usage of synonymous codons in genes with low codon usage bias in yeast and E. coli is examined. The codon adaptation index is employed to identify a group of genes in each organism with low codon usage bias, which are likely to be weakly expressed. A similar pattern is found in complementary sequences with respect to synonymous usage of A vs G or of U vs C. It is suggested that this may reflect an effect of context on mutation rates in weakly expressed genes. PMID- 2190184 TI - Ordered deletions for DNA sequencing and in vitro mutagenesis by polymerase extension and exonuclease III gapping of circular templates. AB - A simple method is described for generating nested deletions from any fixed point in a cloned inset. Starting with a single-stranded phagemid template, T4 DNA polymerase is used to extend an annealed primer. This leads to a fully double stranded circular molecule with a nick or small gap just 5' to the primer. Exonuclease III initiates progressive digestion from the resulting 3' end. Removal of timed aliquots and digestion with a single-strand specific endonuclease leads to a series of linear nested fragments having a common end corresponding to the 5' end of the primer. These molecules are circularized and used to transform cells, providing large numbers of deletion clones with targeted breakpoints. The 6-step procedure involves successive additions to tubes, beginning with a single-stranded template and ending with transformation; no extractions, precipitations or centrifugations are needed. Results are comparable to those obtained with standard Exonuclease III-generated deletion protocols, but there is no requirement for restriction endonuclease digestion or for highly purified double-stranded DNA starting material. This procedure provides a strategy for obtaining nested deletions in either direction both for DNA sequencing and for functional analysis. PMID- 2190185 TI - Oligonucleotide correlations between infector and host genomes hint at evolutionary relationships. AB - The frequencies of oligonucleotides of length 3-6 were studied in 211 sequences of human DNA (659 kilobases), 22 sequences of DNA of human viruses (120 kbs), in 181 sequences of E. coli (442 kbs), and in 42 sequences of phages of E. coli (137 kbs). The sequences were obtained from Genbank(R) 48. The observed frequencies (O) were compared to the expected frequencies (E) obtained in two ways: 1) according to nucleotide composition for each series, and 2) according to first order Markow chains for triplets, second order for quadruplets, and third order for quintuplets and sextuplets. The ratio O/E was obtained for each oligonucleotide. Then, the correlation between the ratio O/E in a pair of series was calculated. Strong correlations were observed for sequences of man and human viruses, and for E. coli and its phages. Other correlations were small. For higher order Markov chains, there is indication of some correlation also between viruses and phages. It was concluded that through analysis of parallel oligonucleotide series it may be possible to infer some of the complex evolutionary relationships existing between cells and their infectors beyond the level of codon usage. PMID- 2190186 TI - Nucleotide sequence of the yeast UGA1 gene encoding GABA transaminase. PMID- 2190187 TI - Sequence of the distal end of E. coli ribosomal RNA rrnG operon. PMID- 2190188 TI - DNA sequence of the putP gene from Salmonella typhimurium and predicted structure of proline permease. PMID- 2190189 TI - The nucleotide sequence of leuC from Salmonella typhimurium. PMID- 2190190 TI - PCR amplification of an Escherichia coli gene using mixed primers containing deoxyinosine at ambiguous positions in degenerate amino acid codons. PMID- 2190191 TI - A rapid and simple method for preparation of RNA from Saccharomyces cerevisiae. PMID- 2190192 TI - Vector-Alu PCR: a rapid step in mapping cosmids and YACs. PMID- 2190193 TI - Management of chemotherapy-induced nausea and vomiting. AB - Cancer chemotherapy is associated with numerous toxicities such as nausea and vomiting (emesis). The frequency, onset, and duration of emesis depend largely on the emetogenic potential of specific agents. An exact mechanism for chemotherapy induced emesis (CIE) is not known but is thought to occur through several noxious actions and numerous neuronal pathways. The three types of CIE are acute, delayed, and anticipatory. Nonchemotherapy causes of emesis should be considered before diagnosing CIE. Once the diagnosis is established, antiemetic regimens should be recommended based on characteristics of the patients and the agents. Phenothiazines, butyrophenones, cannabinoids, metoclopramide, corticosteroids, and benzodiazepines have been successful in preventing and treating CIE. Combinations of these drugs have also been successful and are still being investigated for improved emetic protection with fewer adverse reactions. Investigational agents such as serotonin antagonists may prove to be effective with few toxic effects. Despite the minimal information available on delayed and anticipatory nausea and vomiting, attempts should be made to treat them. Suggested guidelines for the management of CIE have been developed. PMID- 2190194 TI - Oral clindamycin and ciprofloxacin therapy for diabetic foot infections. AB - Infected foot ulcers are a common complication in persons with diabetes. In general, treatment consists of intravenous administration of antibiotics, for which the patients are customarily hospitalized. The average length of hospital stay for this therapy in our institution is 15.6 days. We evaluated a regimen of oral clindamycin plus ciprofloxacin, which patients could take at home, with respect to the clinical eradication of the infection and treatment cost savings. Our results demonstrated that with these oral agents, patients' length of hospital stay was greatly reduced, and the pharmacy realized significant cost avoidance. PMID- 2190195 TI - Etiology of congenital heart defects. PMID- 2190196 TI - Polymerase chain reaction. PMID- 2190197 TI - Acid hematin pigmentation of the cornea in stillborn fetuses. AB - During the postmortem histopathologic evaluation of eyes from stillborn fetuses we noted the presence of a prominent undescribed corneal pigment in 18 of 55 stillborn fetuses. The corneal pigment was frequently associated with documented meconium-stained amniotic fluid, and in no instance was a stained cornea coupled with recorded clear amniotic fluid. Pigmented corneas came from stillborn fetuses with a longer duration of intrauterine death than nonstained corneas. The pigment stained black with the Fontana-Masson stain, was birefringent, and treatment of tissue sections with 5% potassium permanganate and 5% oxalic acid as well as with saturated alcoholic picric acid solution removed the pigment indicating that it is acid hematin. The most likely cause of the acid hematin-stained corneas was tissue acidity created in utero with prolonged intrauterine death. PMID- 2190198 TI - Monoclonal antibody MT1: a marker for Langerhans cell histiocytosis. AB - Langerhans cells and their pathologic counterparts can be identified in paraffin sections using immunohistochemical staining for S-100 protein. This procedure is useful in confirming a diagnosis of Langerhans cell histiocytosis (LCH). However, many other cell types are also positive for S-100 protein. Positive staining for CD1 (Leu 6) supports a diagnosis of LCH, but requires frozen tissue. A panel of antibodies would be desirable in confirming a diagnosis of LCH, particularly if these antibodies could be used on paraffin-embedded material. We studied the pattern of staining for commercially available monoclonal antibodies MT1, MT2, MB2, and LN1, which were originally marketed as lymphocyte markers, using paraffin-embedded tissue sections of cases of LCH. In all 20 cases pathologic Langerhans cells stained positively with MT1 only. Various other S-100 protein positive lesions were also examined with MT1 and were consistently negative for MT1. Other cutaneous histiocytic and mast cell lesions were positive with MT1, but S-100 protein negative. Our results demonstrate that the monoclonal antibody MT1 serves as an additional marker for LCH and, together with S-100 protein, would make up a diagnostic panel of antibodies for LCH to be used on routine paraffin-embedded sections. PMID- 2190200 TI - The physicians' role in the clinical development of new medicines. PMID- 2190201 TI - Adverse effects of captopril in hospital outpatients with hypertension. AB - Hypertensive patients prescribed captopril while attending a hospital hypertension clinic were studied, to identify the benefits of the drug, its adverse effects and factors predisposing to them. One hundred and eighty two patients were followed for a mean of 18 months; 24 received captopril alone, and 158 combinations of captopril and other antihypertensive drugs, especially loop diuretics (91/158), or thiazide diuretics (57/158), or other vasodilators (57/158). The mean final dose of captopril was 67 mg/day. Blood pressure (BP) was effectively controlled in 73% of patients (mean fall in systolic BP 29 mmHg, CI 24 to 34, P less than or equal to 0.001; mean fall in diastolic BP 18 mmHg, CI 16 to 20, P less than or equal to 0.001). Blood urea and creatinine rose slightly in all patients (urea by 0.9 mmol/l [13%], CI 0.5-1.3, P less than or equal to 0.001 and creatinine by 9 mumols/l [8%], CI 4-13, P less than or equal to 0.001). Twenty six patients were withdrawn from captopril therapy: 6 because of poor control of their blood pressure, two because it was no longer necessary and 12 (7.7%) because of extrarenal adverse effects--10 for rashes, one each for gastric upset and impotence. Captopril was withdrawn in a further 6 patients, because of deteriorating renal function. Factors discriminating those at risk of renal dysfunction were high doses of captopril, concomitant high dose diuretic therapy and undiagnosed renovascular disease. PMID- 2190202 TI - Survival after ultrasonographic demonstration of portal venous gas due to mesenteric artery occlusion. AB - Portal vein gas as a result of bowel necrosis following occlusion of the superior mesenteric artery has an extremely grave prognosis. Only two previous cases have been recorded as having survived. In both those cases the diagnosis of portal vein gas was made on an abdominal radiograph. The present report is of the first such case surviving after ultrasonic demonstration of portal gas. In this case, no evidence of portal gas was seen on the abdominal radiograph. The increased sensitivity of ultrasound over plain radiography mandates urgent liver and portal ultrasound in all cases of suspected mesenteric event. PMID- 2190199 TI - Respiratory diseases. PMID- 2190203 TI - Anti-neutrophil cytoplasmic antibodies and vasculitis. PMID- 2190205 TI - [Biosensors and their applications (review of the literature)]. AB - Different biosensors (potentiometric, voltampermetric, thermometric, optoelectronic, acoustoelectronic) are reviewed, and the main principles of their operation are discussed. Data on biosensor applications are systematized. PMID- 2190206 TI - [Construction of the gene library of symbiotic nitrogen-fixing Rhizobium lupini]. AB - The gene bank of the symbiotic nitrogen-fixing bacterium Rhizobium lupini (effective strain 359a) was constructed on plasmid pAYC31 that was used to transform Escherichia coli C6000. The bank contains 6600 clones. Restriction analysis showed that the size of the mean insertion fragment in the plasmid in 6.5 kb. PMID- 2190204 TI - Oncology. PMID- 2190207 TI - [Stability of biocatalysts on the basis of carrageenan-immobilized Escherichia coli during continuous synthesis of L-malic acid]. AB - Continuous enzymatic synthesis of L-malic acid from potassium fumarate in packed bed flow reactors was investigated. Carrageenan-immobilized Escherichia coli cells were used as a biocatalyst. The operational stability of the biocatalyst fumarase activity was studied, and conditions for preserving high activity of the biocatalyst were determined. PMID- 2190209 TI - [The effect of bacteriolytic preparation lysoamidase on Staphylococcus aureus 209P cells]. AB - The effect of the bacteriolytic preparation "Lysoamidase" on Staphylococcus aureus 299 P was studied. The maximum activity of the preparation was observed at pH 8.0 ionic strength 0.01-0.02 M and 50-60 degrees of the incubation medium. The electron microscopic examination revealed that "Lysoamidase" hydrolyzed the cell wall in one or several points with the following osmotic shock and extrusion of the cytoplasm. In an isotonic solution (1 M sucrose) "Lysoamidase" caused protoplast formation. PMID- 2190208 TI - [Enzymes of thiol-disulfide metabolism of proteins]. AB - Occurrence, properties and physiological role of protein disulfide reductases (EC 1.6.4.4 and 1.8.4.2), protein disulfide isomerase (EC 5.3.4.1), and thiol oxidase (EC 1.8.3.2) catalyzing thiol-disulfide interchange reactions in proteins are reviewed with a particular emphasis on seed storage proteins. An important role of the enzymes in the formation and degradation of seed storage protein complexes is discussed. PMID- 2190210 TI - Flagellin as an object for supramolecular engineering. AB - A model of tertiary and quaternary structure of E. coli flagellin is suggested. According to this model, the molecule consists of two independent parts. One of them is formed by the N- and C-terminal regions of the polypeptide chain and is responsible for polymerization properties. The other consists of the central region of the polypeptide chain and composes that part of the molecular globule that forms the flagella surface. It is suggested that different artificial supramolecular structures can be constructed from flagellin molecules by varying the surface domain, i.e. the central part of the polypeptide chain, and by using the domain responsible for polymerization properties as a universal block for assembly. The simplest possible artificial supramolecular structures that can be constructed from flagellins of different strains are discussed. PMID- 2190211 TI - Expression of goat alpha-lactalbumin in Escherichia coli and its refolding to biologically active protein. AB - A cDNA encoding the mature region of goat alpha-lactalbumin and the 3'-non-coding region was fused to cDNA of the N-terminal half of porcine adenylate kinase which had been placed under the control of the tac promoter in an expression vector in Escherichia coli. In addition, a methionine codon was inserted between the two cDNAs. When the plasmid carried the full-length 3'-non-coding region, little accumulation of the fused protein was observed. However, the deletion of two thirds of the 3'-non-coding region produced significant expression of the fused protein in E. coli strain JM105. Since goat alpha-lactalbumin contains no methionine residue, the mature goat alpha-lactalbumin was isolated by CNBr digestion of the fused insoluble protein and refolded using thioredoxin. The homogeneous and biologically active goat alpha-lactalbumin was purified by Ca2+ ion-dependent hydrophobic chromatography. PMID- 2190212 TI - Peptidyl-prolyl cis-trans-isomerase from Escherichia coli: a periplasmic homolog of cyclophilin that is not inhibited by cyclosporin A. AB - The prokaryotic peptidyl-prolyl cis-trans-isomerase called "rotamase", a homolog of the human cyclophilin, has been identified in Escherichia coli. The E. coli rotamase, a product of the gene we suggest be called "rot," has been purified to homogeneity after cloning of the gene by the polymerase chain reaction and its overexpression in E. coli. Based on the chymotrypsin-coupled assay using the tetrapeptide substrate succinyl-Ala-Ala-Pro-Phe-p-nitroanilide, the purified protein has rotamase activity identical to human cyclophilin with a catalytic efficiency close to the upper diffusional limit (kcat/Km approximately 1.0 x 10(7) M-1 x S-1 at 10 degrees C). Unlike the human cyclophilins, however, the E. coli rotamase is not significantly inhibited by the immunosuppressant drug cyclosporin A. By spheroplast fractionation of cells harboring the expression vector for the complete rot gene, the rotamase is located in the periplasm, where it could function in refolding of secreted proteins. PMID- 2190213 TI - Mitogenic stimulation of human tumor-infiltrating lymphocytes by secreted factor(s) from human tumor cell lines. AB - Tumor-infiltrating lymphocytes (TILs) have shown in vivo antitumor efficacy in both animal and human studies. Functions thought necessary for antitumor activity include cytolysis, homing, and proliferation at tumor sites. TILs, which are T lymphocytes grown ex vivo directly from tumors, bear interleukin 2 (IL-2) receptors capable of transducing the IL-2 mitogenic signal. However, IL-2 is not normally synthesized by solid tumor cells. This study was aimed at exploring the possible presence of T-cell mitogens of tumor origin. To this end four TIL lines derived from four melanoma patients were studied for their ability to use the environments of cultured tumor cell lines as mitogenic sources. The presence of four irradiated cultured human tumor cell lines, three of which were derived from the same melanoma patients as the TILs, were found to stimulate proliferation of human TILs in the absence of IL-2. Further investigation showed that the observed proliferative stimulation by the fourth tumor line was due to secreted factor(s) as mitogenic activity was present in the serum-free tumor cell supernatant. Both immunologic analyses of this medium and proliferative assays in which TILs were stimulated with recombinant lymphokine standards suggest the presence of a yet uncharacterized T-cell mitogen. PMID- 2190215 TI - Differential protein expression by Shigella flexneri in intracellular and extracellular environments. AB - Shigellae were intrinsically radiolabeled with [35S]methionine either extracellularly or while multiplying within infected HeLa cell monolayers. A complex pattern of suppression and induction of proteins was observed. Proteins of approximately 97, 62, 58, 50, 25, and 18 kilodaltons (kDa) were induced in Shigella flexneri isolated from infected monolayers. Proteins of 100, 85, 70, 64, and 55 kDa were suppressed under the same conditions but were seen in cells labeled in the tissue culture medium alone. Protein expression during the stages of attachment, invasion, and intracellular multiplication was examined by pulse labeling. The 58-kDa protein was induced only during invasion, and the 62- and 25 kDa proteins were induced only during intracellular multiplication. Shift into a minimal medium with ion concentrations and pH mimicking intracellular conditions and endosomal pH resulted in the induction of the 97- and 58-kDa proteins, and reduction of the intracellular-like medium with 2-mercaptoethanol resulted in the induction of the 97-, 50-, and 25-kDa proteins and suppression of the 55-kDa protein. Radioimmunoprecipitations of shigellae grown in vitro and in vivo revealed differential expression of immunogenic proteins. Proteins corresponding in size to IpaB (62 kDa), IpaC (42 kDa), and IpaD (38 kDa) were lost during intracellular multiplication, whereas another protein corresponding to IpaA (80 kDa) was found to increase under the same conditions. PMID- 2190214 TI - Regulation of beta-cell glucose transporter gene expression. AB - It has been postulated that a glucose transporter of beta cells (GLUT-2) may be important in glucose-stimulated insulin secretion. To determine whether this transporter is constitutively expressed or regulated, we subjected conscious unrestrained Wistar rats to perturbations in glucose homeostasis and quantitated beta-cell GLUT-2 mRNA by in situ hybridization. After 3 hr of hypoglycemia (glucose at 29 +/- 5 mg/dl), GLUT-2 and proinsulin mRNA signal densities were reduced by 25% of the level in control rats. After 4 days (blood glucose at 57 +/ 7 mg/dl vs. 120 +/- 10 mg/dl in saline-infused control rats), GLUT-2 and proinsulin mRNA densities were reduced by 85% and 65%, respectively (P = 0.001). After 12 days (glucose at 54 +/- 8 mg/dl), GLUT-2 mRNA signal density was undetectable whereas proinsulin mRNA was reduced by 51%. After 12 days of hypoglycemia, the Km for 3-O-methyl-D-glucose transport in isolated rat islets, normally 18-20 mM, was 2.5 mM. This provides functional evidence of a profound reduction of high Km glucose transporter in beta cells. In contrast, GLUT-2 was only slightly reduced by hypoglycemia in liver. To determine the effect of prolonged hyperglycemia, we also infused animals with 50% (wt/vol) glucose for 5 days (glucose at 200 +/- 50 mg/dl). Hyperglycemic clamping increased GLUT-2 mRNA by 46% (P = 0.001) whereas proinsulin mRNA doubled (P = 0.001). We conclude that GLUT-2 expression in beta cells, but not liver, is subject to regulation by certain perturbations in blood glucose homeostasis. PMID- 2190216 TI - Protection of mice against tumor growth by immunization with an oncogene-encoded growth factor. AB - The K-fgf/hst oncogene encodes a growth factor of the fibroblast growth factor (FGF) family that is secreted and transforms cells through a mechanism of autocrine cell proliferation. K-fgf-transformed cells are highly tumorigenic in immunocompetent allogeneic and syngeneic animals. BALB/c mice were immunized with a bacterial fusion protein consisting of a portion of the MS2 polymerase and of the human K-FGF precursor lacking only the first 4 amino acids or with a recombinant protein corresponding to the mature, secreted form of K-FGF (176 amino acids). They were then challenged with syngeneic K-fgf- or H-ras transformed cells. Vaccinated animals exhibited a significant degree of protection against tumor induction, which was specific for K-fgf-transformed cells and correlated with the ability of the immunized mice to produce high titers of anti-K-FGF antibodies. Thus immunization with a single oncogene product can protect animals against tumor cells expressing this oncogene. PMID- 2190217 TI - Construction and characterization of a yeast artificial chromosome library containing seven haploid human genome equivalents. AB - Prior to constructing a library of yeast artificial chromosomes (YACs) containing very large human DNA fragments, we performed a series of preliminary experiments aimed at developing a suitable protocol. We found an inverse relationship between YAC insert size and transformation efficiency. Evidence of occasional rearrangement within YAC inserts was found resulting in clonally stable internal deletions or clonally unstable size variations. A protocol was developed for preparative electrophoretic enrichment of high molecular mass human DNA fragments from partial restriction digests and ligation with the YAC vector in agarose. A YAC library has been constructed from large fragments of DNA from an Epstein-Barr virus-transformed human lymphoblastoid cell line. The library presently contains 50,000 clones, 95% of which are greater than 250 kilobase pairs in size. The mean YAC size of the library, calculated from 132 randomly isolated clones, is 430 kilobase pairs. The library thus contains the equivalent of approximately seven haploid human genomes. PMID- 2190218 TI - Glucose transporters are abundant in cells with "occluding" junctions at the blood-eye barriers. AB - We studied the distribution of the "erythroid/brain" glucose transporter protein in the human and rat eye by immunocytochemistry with monoclonal and polyclonal antibodies to the C terminus of the human erythrocyte glucose transporter. We found intense immunocytochemical staining in the endothelium of microvessels of the retina, optic nerve, and iris but not in microvessels of the choroid, ciliary body, sclera, and other retro-orbital tissues. In addition, we found marked immunocytochemical staining of retinal pigment epithelium, ciliary body epithelium, and posterior epithelium of the iris. The common feature of all those endothelial and epithelial cells that stained intensely for the glucose transporter is the presence of "occluding" intercellular junctions, which constitute the anatomical bases of the blood-eye barriers. We propose that a high density of the glucose transporter is a biochemical concomitant of epithelial and endothelial cells with barrier characteristics, at least in tissues that have a high metabolic requirement for glucose. PMID- 2190219 TI - Localization of cellular retinol-binding protein and retinol-binding protein in cells comprising the blood-brain barrier of rat and human. AB - Brain is not generally recognized as an organ that requires vitamin A, perhaps because no obvious histologic lesions have been observed in severely vitamin A deficient animals. However, brain tissue does contain cellular vitamin A-binding proteins and a nuclear receptor protein for retinoic acid. In the present study, immunohistochemical techniques were used to determine the cell-specific location of cellular retinol-binding protein in human and rat brain tissue. Cellular retinol-binding protein was localized specifically within the endothelial cells of the brain microvasculature and within the cuboidal epithelial cells of the choroid plexus, two primary sites of the mammalian blood-brain barrier. In addition, autoradiographic procedures demonstrated binding sites for serum retinol-binding protein in the choroidal epithelium. These observations suggest that a significant movement of retinol across the blood-brain barrier may occur. PMID- 2190220 TI - In vivo expression of the lacY gene in two segments leads to functional lac permease. AB - The lacY gene of Escherichia coli was cut into two approximately equal-size fragments with Afl II and subcloned individually or together under separate lac operator/promoters in plasmid pT7-5. Under these conditions, lac permease is expressed in two portions: (i) the N-terminal portion (the N terminus, the first six putative transmembrane helices, and most of putative loop 7) and (ii) the C terminal portion (the last six putative transmembrane helices and the C terminus). Cells harboring pT7-5 encoding both fragments transport lactose at about 30% the rate of cells expressing intact permease to a comparable steady state level of accumulation. In contrast, cells expressing either half of the permease independently do not transport lactose. As judged by [35S]methionine labeling and immunoblotting, intact permease is completely absent from the membrane of cells expressing lacY fragments either individually or together. Thus, transport activity must result from an association between independently synthesized pieces of lac permease. When the gene fragments are expressed individually, the N-terminal portion of the permease is observed inconsistently, and the C-terminal portion is not observed. When the gene fragments are expressed together, polypeptides identified as the N- and C-terminal moieties of the permease are found in the membrane. It is concluded that the N- or C-terminal halves of lac permease are proteolyzed when synthesized independently and that association between the two complementing polypeptides leads to a more stable, catalytically active complex. PMID- 2190221 TI - Association of the fyn protein-tyrosine kinase with the T-cell antigen receptor. AB - Activation of the T-cell antigen receptor (TCR) results in tyrosine phosphorylation of the TCR zeta chain and other intracellular substrates. Two other T-cell integral membrane proteins, CD4 and CD8, are associated with the protein-tyrosine kinase (PTK), lck. Despite evidence that activation of this enzyme results in TCR-zeta chain phosphorylation, it has not been shown that the TCR activates lck. We have sought evidence that the TCR is associated with a PTK. In this study we use digitonin to solubilize a murine T-cell hybridoma and demonstrate that antibodies binding extracellular but not intracellular domains of the TCR specifically coprecipitate only the fyn PTK and not lck or yes, two other kinases found in these cells. The association of the fyn PTK with the TCR might enable the T cell to independently regulate two PTKs through surface receptors. PMID- 2190223 TI - Food preservatives and the microbiological consequences of their reduction or omission. PMID- 2190222 TI - Early transcription factor subunits are encoded by vaccinia virus late genes. AB - The vaccinia virus early transcription factor (VETF) was shown to be a virus encoded heterodimer. The gene for the 82-kDa subunit was identified as open reading frame (ORF) A8L, based on the N-terminal sequence of factor purified by using DNA-affinity magnetic beads. The 70-kDa subunit of VETF was refractory to N terminal analysis, and so N-terminal sequences were obtained for three internal tryptic peptides. All three peptides matched sequences within ORF D6R. ORFs A8L and D6R are located within the central region of the vaccinia virus genome and are separated by about 13,600 base pairs. Proteins corresponding to the 3' ends of ORFs A8L and D6R were overexpressed in Escherichia coli and used to prepare antisera that bound to the larger and smaller subunits, respectively, of affinity purified VETF. Immunoblot analysis of proteins from infected cells indicated that both subunits are expressed exclusively in the late phase of infection, just prior to their packaging in virus particles. The two subunits of VETF have no significant local or overall amino acid sequence homology to one another, to other entries in biological sequence data bases including bacterial sigma factors, or to recently determined sequences of some eukaryotic transcription factors. The 70-kDa subunit, however, has motifs in common with a super-family of established and putative DNA and RNA helicases. PMID- 2190224 TI - Nutritional recommendations for n-3 polyunsaturated fatty acids and the challenge to the food industry. PMID- 2190225 TI - Implications of nutritional recommendations on sugar for product development. PMID- 2190226 TI - Food fortification. PMID- 2190227 TI - Calcium as an intracellular regulator. PMID- 2190229 TI - Intracellular calcium, cell injury and relationships to free radicals and fatty acid metabolism. PMID- 2190228 TI - Intracellular calcium ions and intramitochondrial Ca2+ in the regulation of energy metabolism in mammalian tissues. PMID- 2190230 TI - Intra- and extracellular calcium and hypertension. PMID- 2190231 TI - Vitamin D and other extracellular factors in the control of growth. PMID- 2190232 TI - Effect of nephrectomy and of adrenergic receptor blockers on the cardiorenal actions of endothelin. AB - The cardiorenal actions of endothelin-1 (ET-1) were evaluated in rats following nephrectomy, in rats during alpha-adrenergic blockade with phentolamine, and in rats during beta-adrenergic blockade with propranolol. Female rats were anesthetized with pentobarbital and, following surgery, were allowed 60 min to stabilize before 3 x 20 min-control clearances were collected. ET-1 was then infused at a rate of 100 ng kg-1 min-1 for 30 min, the infusion was stopped, and three additional clearances were collected. Four groups of rats were studied: in Group 1 (n = 10), ET-1 was infused; in Group 2 (n = 5), a bilateral nephrectomy was performed 120 min before infusing ET-1; in Group 3 (n = 5), ET-1 was infused into rats treated with phentolamine (0.015 mg kg-1 min-1); and in Group 4 (n = 5), ET-1 was infused into rats treated with propranolol (0.015 mg kg-1 min-1). At 30 min during infusion of ET-1 into Group 1 rats, mean arterial blood pressure had increased (P less than 0.01) by 27 +/- 2% (SE) and the glomerular filtration rate had decreased (P less than 0.01) by 71 +/- 6% of baseline values. Nephrectomy potentiated and prolonged the ET-1-induced systemic vasoconstriction. Phentolamine had no effect on the cardiorenal actions of ET-1 whereas propranolol enhanced ET-1-induced changes in mean arterial blood pressure; mean arterial blood pressure increased 38 +/- 2% at 30 min during ET-1 + propranolol infusion (P less than 0.01 versus value with ET-1 alone). These data indicate that the kidney affects ET-1-induced systemic vasoconstriction and that beta-adrenergic (but not alpha-adrenergic) receptors are activated during infusion of ET-1 with a resultant attenuation of ET-1-induced changes in systemic blood pressure. PMID- 2190233 TI - Stereostructure activity relationships of catecholamines on human platelet function. AB - The concentration-dependent effects of clonidine, isomers of epinephrine, norepinephrine (NE), isoproterenol, cobefrin and alpha-methyldopamine, and related desoxy analogs (epinine, dopamine, N-isopropyldopamine) were examined on human platelets. The rank order of aggregatory potency (pD2 values) was R(-) epinephrine (6.3) greater than R(-)-NE (5.9) greater than (+/-)-erythro-cobefrin (5.3) greater than S(+)-epinephrine (4.7) = S(+)-NE (4.7) = clonidine (4.7) = dopamine (4.6) greater than epinine (4.4) greater than S(+)-alpha-methyldopamine (4.3) = R(-)-alpha-methyldopamine (4.3) greater than (+/-)-threo-cobefrin (3.7). The isoproterenol isomers and N-isopropyl-dopamine were inactive as agonists. In 9 of 16 platelet-rich plasma preparations, R(-)-epinephrine, R(-)-NE, and (+/ )erythro-cobefrin were agonists and the remaining analogs blocked R(-)-NE-induced aggregation with a rank order of inhibitory potencies (pKB values) of clonidine (6.2) greater than S(+)-alpha-methyldopamine (5.0) greater than dopamine (4.6) = R(-)-alpha-methyldopamine (4.4) greater than or equal to S(+)-NE (4.3) greater than N-isopropyldopamine (4.1) greater than S(+)-isoproterenol (3.7) = R(-) isoproterenol (3.5). Each compound was also able to reverse prostaglandin E1 (PGE1) (0.1 microM)-induced blockade of the maximal aggregation response to ADP. At high concentrations, R(-)-isoproterenol was more potent than either the S(+) isomer or desoxy analog, N-isopropyldopamine, in the reversal of PGE1 inhibition of ADP aggregation. Phentolamine blocked these alpha 2-adrenoceptor-mediated actions against PGE1 on ADP aggregation. The rank order of potency for the reversal of PGE1-mediated inhibition of ADP aggregation by these catecholamines was similar to that observed for platelet aggregation. Our results indicate that (i) the stereochemical requirements for the interaction of catecholamines with platelet alpha 2-adrenoceptors are in agreement with the Easson-Stedman hypothesis and other alpha-adrenoceptor tissues; (ii) catecholamines lacking a benzylic hydroxyl group in the R-configuration and/or possessing an N-isopropyl group were alpha 2-adrenoceptor antagonists; (iii) clonidine gave quantitatively different responses compared with catecholamines for interaction with alpha 2 adrenoceptors; and (iv) inhibition of platelet adenylate cyclase is correlated to the inhibition of epinephrine-induced aggregation response for this series of compounds. PMID- 2190235 TI - The myogenic lineage: evidence for multiple cellular precursors during avian limb development. PMID- 2190234 TI - Production of a novel monoclonal antibody to porcine adipocyte plasma membrane. AB - The adipocyte plasma membrane is composed of specific intrinsic, integral, and extrinsic proteins. The study of adipocyte development, morphology, and metabolism has been limited by a lack of characterization of these proteins. It seems likely that the adipocyte plasma membrane possesses adipocyte-specific proteins which may be linked to the unique identity of adipose tissues. To study the composition of the adipocyte plasma membrane, we produced a panel of monoclonal antibodies to purified adipocyte plasma membranes. Nineteen anti adipocyte hybridoma cell lines were identified using fluorescent enzyme-linked immunosorbent assay, immunoblotting, and indirect immunofluorescence. A monoclonal antibody (designated LA-1) with reactivity toward a porcine adipocyte plasma membrane component was used for further adipocyte characterization. LA-1 reacted with a species-specific 64-kDa protein expressed in adipocyte plasma membranes but not in hepatocyte, erythrocyte, skeletal muscle, heart, spleen, kidney, stomach, small intestine, or large intestine plasma membranes. The LA-1 antibody provides a specific probe for this adipocyte surface protein marker. PMID- 2190236 TI - Effects of insulin-like growth factors and transforming growth factor-beta on the growth and differentiation of muscle cells in culture. PMID- 2190237 TI - Regulation of satellite cells during skeletal muscle growth and development. AB - Satellite cells are myogenic cells attributed with the role of postnatal growth and regeneration in skeletal muscle. Following proliferation and subsequent differentiation, these cells will fuse with one another or with the adjacent muscle fiber, thereby increasing myonuclei numbers for fiber growth and repair. The potential factors which could regulate this process are many, including exercise, trauma, passive stretch, innervation, and soluble growth factors. Three classes of growth factors in particular (fibroblast growth factor, insulin-like growth factor, and transforming growth factor-beta) have been studied extensively with respect to their effects on satellite cell proliferation and differentiation in culture. Fibroblast growth factor has been shown to stimulate proliferation but depress differentiation. Insulin-like growth factor stimulates both proliferation and differentiation, although the latter to a much greater degree. Transforming growth factor-beta slightly depresses proliferation but inhibits differentiation. When administered in combination, these factors can induce satellite cell activities in culture which mimic those typical of satellite cells found in vivo in growing, regenerating, or healthy mature muscle. Alterations in the concentrations of these growth factors in the muscle environment as well as alterations in the cell's sensitivity or responsiveness to these factors represent potential mechanisms for regulating satellite cell activity in situ. PMID- 2190238 TI - Developmental and maturational aspects of inherited avian myopathies. AB - Three inherited abnormalities of muscle growth of poultry are an inherited muscular dystrophy of the chicken, deep pectoral myopathy of turkeys and broilers, and focal myopathy of turkeys. The major features of each are described and compared. Cellular and molecular bases of dystrophy of the chicken and treatments to alleviate the disorder are discussed. The pathologic progression and anatomical basis for deep pectoral myopathy are presented. Evidence is given that focal myopathy of the turkey is a growth-dependent disorder. The implications of the idea that such disorders are partly consequences of selection are discussed in the context of the future needs of a poultry industry emphasizing processing of poultry meat. PMID- 2190239 TI - The noncompetitive N-methyl-D-aspartate antagonists, MK-801, phencyclidine and ketamine, increase the potency of general anesthetics. AB - The potency of general anesthetics from different chemical classes was tested after pretreatment with subanesthetic doses of noncompetitive N-methyl-D aspartate (NMDA) antagonists in mice. Changes in general anesthetic potency were assessed by determination of alteration of duration of loss of righting reflex for ethanol and pentobarbital and changes in the minimum alveolar concentration (MAC) for the volatile anesthetics, halothane and diethyl ether. The ability of the noncompetitive NMDA antagonists, MK-801 [(+)-5-methyl-10,11-dihydro-5H dibenzo(a,d)cyclo-hepten-5,10-imine ], phencyclidine (PCP) and ketamine, to increase the potency of general anesthetics paralleled their potency as NMDA antagonists and their affinity for the PCP receptor site of the NMDA receptor ionophore complex (MK-801 greater than PCP greater than ketamine). These results indicate that block of central NMDA receptors may contribute to the production of anesthesia by a variety of agents. PMID- 2190240 TI - 1989 Douglas Lea memorial lecture. The cell dose concept; potential application in radiation protection. PMID- 2190241 TI - A patient rotator for stereotactic radiosurgery. AB - A new technique for stereotactic radiosurgery by use of a patient rotator is described. Using the rotator with a small collimated beam of 6 MV x-rays, a small well-defined region of the brain can be irradiated to a high dose with rapid fall off of the dose outside the target volume. Since the linear accelerator gantry does not move during therapy the possibility of a collision between the gantry and the patient or stereotactic equipment is eliminated. The system is also independent of the rotational stability of the linear accelerator gantry axis and turntable axis. Dose distributions measured in a Lucite head phantom with film exhibited properties well suited for radiotherapy. Tests carried out to evaluate the ability to irradiate a selected target point within the brain with the rotator system showed a maximum positional error of 1.0 and 2.0 mm for angiography and CT localisation respectively. PMID- 2190242 TI - A technique for digital image registration used prior to subtraction of lung images in nuclear medicine. PMID- 2190243 TI - Functional telomere formation in yeast using synthetic C4A2 sequences. AB - A yeast artificial chromosome (YAC) was constructed with a native autonomous replicating sequence (ARS) flanked telomere at one end and a 50-bp synthetic oligonucleotide of C4A2 repeats at the other. This was done in order to determine whether the presence of the flanking ARS sequence is required for telomere function. This construct was introduced into two different yeast strains: one mutated in the recombination function RAD52 and the other wild type for this gene. Both strains gave rise to autonomously replicating artificial chromosomes. The molecules in the RAD52 strain were rearranged dimers terminating at both ends with Tetrahymena telomeres, whereas in the rad52 strain two classes of YACs were found: rearranged dimers and elements bearing an ARS-free telomere. The presence of the latter class of molecules confirmed the finding of Wellinger and Zakian (1989, Proc. Natl. Acad. Sci. USA 86, 973-977) that the flanking ARS is not required for telomere function. Furthermore, in this class of molecules the ARS free telomeric end was shortened as a result of deletions that removed some distal pBR322 sequences and some C4A2 repeats. The size of the resulting YACs ranged from 7.7 to 9 kb, considerably below the size threshold found by Zakian et al. (1986, Mol. Cell. Biol. 6, 925-932) for CEN4 artificial plasmids. An explanation for the structural instability of the ARS-free end of the YACs is suggested. PMID- 2190244 TI - Expression of the sulfonamide resistance gene from plasmid R46. AB - The expression of the sul I gene from plasmid R46, a wide host range plasmid of the IncN incompatibility group, was studied in Escherichia coli. Using a promoter test vector, a promoter was detected upstream of the sul I gene. From a nuclease protection experiment, the transcription was determined to start 360 bp upstream of the coding sequence. Two putative promoter -35 and -10 sequences were found upstream from the predicted transcription start. The presence of this promoter sequence in other R factors was discussed in relation with previous data showing that the sul I genes were transcribed from other promoters. The translation product of the sul I gene was detected in minicells. Its size indicates that the translation starts at the first ATG codon found in the open reading frame. PMID- 2190245 TI - A phasmid shuttle vector for the cloning of complex operons in Salmonella. AB - Phasmid (phage plasmid hybrid) P4 vir1 can be propagated in Escherichia coli as a helper-dependent lytic phage, as a plasmid, or as a prophage. On the basis of an understanding of these modes of propagation, derivatives of P4 have been constructed for use as cloning vectors. In this report we demonstrate that phasmid P4 (i) will propagate as a helper-dependent lytic phage and as a plasmid in Salmonella spp. and (ii) can be used as a high efficiency phage shuttle vector for the reversible transfer of cloned genes between Salmonella spp. and E. coli. For both E. coli and Salmonella spp., P4 phage-mediated gene transfer proved to be only 10-fold lower than plaquing efficiency. For the case of Salmonella spp., this frequency is ca. 10(4)-fold more efficient than is typically found for the transformation of DNA molecules. The usefulness of this cloning vector system for analyses of pathogenic virulence factors is demonstrated by the cloning and expression of both the P pilus adhesin operon and the hemolysin operon of uropathogenic E. coli. PMID- 2190247 TI - Limb muscle regeneration in peripheral nerve autografts. AB - In a previous study we demonstrated regenerative growth of extraocular muscle within transplanted peripheral nerve autografts. The present study addresses the feasibility of inducing regeneration of limb muscle within autologous peripheral nerve implants in the gluteus medius of beagles. In six anesthetized animals, a 2 cm segment of the left infraorbital sensory nerve was removed from the nose and implanted between the cut ends of several muscle fascicles in the left gluteus medius. After 4 weeks, the nerve grafts were removed and examined by light and electron microscopy. Muscle fibers were seen surrounded by the epineurium of the implanted nerve along its entire length, growing in parallel with the long axis of the nerve. The regenerating fibers were closely associated with the basal lamina of degenerating myelinated and unmyelinated axons. This study suggests that limb muscle, like extraocular muscle, is capable of organized regenerative growth within peripheral nerve autografts. PMID- 2190246 TI - Natural-Y Meme polyurethane versus smooth silicone: analysis of the soft-tissue interaction from 3 days to 1 year in the rat animal model. AB - The polyurethane foam-covered breast prosthesis is experiencing increased clinical use. The polyurethane is felt to be responsible for altering capsule formation and reducing the contracture rate. This study characterizes the soft tissue response to the Natural-Y Meme polyurethane foam versus smooth silicone in a rat model. Implants were fashioned from an unbacked polyurethane foam specimen used to cover the Natural-Y prosthesis, a silicone shell covered with the Natural Y foam, and a smooth silicone control. Materials were placed subcutaneously into the backs of male Lew/SsN rats (n = 81) for 3, 7, 14, and 28 days and 3, 6, and 12 months. Implants were then harvested with their soft-tissue response and evaluated histologically. Analysis demonstrates that microstructuring of a surface, as opposed to a smooth material, will dramatically alter the early, intermediate, and late wound-healing events. The soft-tissue response was observed to be dependent on implant site, material chemistry, and morphology as characterized by exudate formation, macrophage invasion, multinucleated giant cell formation, collagen deposition, foam degradation, and angiogenesis. PMID- 2190248 TI - Treatment of vaginal agenesis with a new vulvovaginoplasty. AB - The correction of vaginal agenesis requires the creation of a canal that is in the correct axis and ideally of adequate size, texture, and secretion. A simple surgical technique is described which has a good anatomic and functional result with minimal morbidity. It combines the traditional dissection of the rectovesical space described by McIndoe with a significantly modified vulvovaginoplasty based on the Williams method. The technique has been performed with good results and no complications in three patients. Closely monitored vaginal dilatation is essential in the postoperative period. At this stage, only one patient has engaged in intercourse. PMID- 2190249 TI - Open rhinoplasty without skin-columella incision. AB - For the last 4 years, the author has been using the open lower cartilaginous vault rhinoplasty, making an external cutaneous incision on the columella. After observing the improved results in patients with nasal tip, lateral crura, and medial crura difficulties, the author widely recommends the use of this procedure in selected patients. In addition to multiple advantages which have been reported useful in open-tip rhinoplasty in the past, the author has contributed two additional advantages: that it avoids scarring columella skin and that it can be extended to cope with defects of the entire lower cartilaginous vault. Disadvantages are some residual edema in some patients over a 6-months period and prolongation of operating time. PMID- 2190250 TI - Bipedicled flaps for the nasal tip. PMID- 2190251 TI - Pharmacological effects of methylphenidate on plasma homovanillic acid and growth hormone. AB - The acute pharmacological actions of methylphenidate, a potent psychotogenic stimulant, were studied by measuring plasma homovanillic acid (HVA) and serum growth hormone (GH) as indices of presynaptic and postsynaptic functions, respectively. Twenty psychiatric inpatients participated in a double-blind, placebo-randomized study of methylphenidate infusion. Multiple samples of plasma HVA and GH were measured before and up to 24 hours after both methylphenidate and placebo infusions. There was a robust and significant GH response during the 2 hour postmethylphenidate period when compared to placebo. The peak response was significantly greater in male patients than in female patients. Although there were no changes in plasma HVA during the 2 hours following the infusion, there was a significant decrease in HVA 24 hours after methylphenidate as compared to preinfusion baseline values. Plasma HVA values also tended to be lower 24 hours after methylphenidate when compared to the corresponding postplacebo value. Schizophrenic patients did not differ significantly from nonschizophrenic patients in their physiological or biochemical responses. PMID- 2190252 TI - Why we still use our heads instead of formulas: toward an integrative approach. AB - This review begins with a discussion of Meehl's (1957) query regarding when to use one's head (i.e., intuition) instead of the formula (i.e., statistical or mechanical procedure) for clinical prediction. It then describes the controversy that ensued and analyzes the complexity and contemporary relevance of the question itself. Going beyond clinical inference, it identifies select cognitive biases and constraints that cause decision errors, and proposes remedial correctives. Given that the evidence shows cognition to be flawed, the article discusses the linear regression, Bayesian, signal detection, and computer approaches as possible decision aids. Their cost-benefit trade-offs, when used either alone or as complements to one another, are examined and evaluated. The critique concludes with a note of cautious optimism regarding the formula's future role as a decision aid and offers several interim solutions. PMID- 2190253 TI - Separating cognitive impairment in neurologically asymptomatic alcoholism from Wernicke-Korsakoff syndrome: is the neuropsychological distinction justified? AB - Recent studies that have combined neuropathological data and clinical histories in a retrospective fashion have shown that Wernicke-Korsakoff neuropathology is often unsuspected antemortem and that, in terms of clinical presentation, it is more heterogeneous than previously assumed. Thus, many studies of neurologically normal alcoholics may have been confounded by the inclusion of patients with neurologically asymptomatic Wernicke-Korsakoff neuropathology. Postmortem and in vivo studies have shown that alcoholics, irrespective of neurological diagnosis, have widespread pathology involving many cortical and subcortical sites. In addition, clinical studies have indicated that, like neurologically asymptomatic alcoholics, alcoholic Korsakoff patients may enjoy substantial recovery in cognitive function. Furthermore, the common research strategy of identifying a subset of neurologically diagnosed Wernicke-Korsakoff syndrome as a discrete group of "pure" Korsakoff's amnesia by using a definitional IQ-Wechsler Memory Scale quotient difference may have created a neuropsychological stereotype that is not representative of the broader clinical group. In light of these considerations, the separate treatment of cognitive impairment in groups of alcoholics distinguished by the clinical signs of Wernicke-Korsakoff syndrome may not be justified. PMID- 2190254 TI - Overcoming the loss of a love: preventing love addiction and promoting positive emotional health. AB - Counseling and clinical observations clarify views commonly made about the pain of breaking-up a love relationship. Anecdotal reports as presented in popular music, novels, movies, and television programs illustrate the public's general awareness of the emotional dilemma of ending a relationship. Love is a strong pleasurable emotional state. Behavioral and emotional problems can result from rejection and the pain due to the loss of a love. The term "love addiction" has been applied to persons who obsessively seek to regain the pleasurable love state which existed with a former love relationship. Dysfunctional emotional conditions such as distrust, feelings of rejection, loss of self-worth, deep-seated anger, feelings of failure, loss, and an array of other emotional distress and self defeating behaviors arise in the emotionally hurt person. Emotional distress must be dealt with. Rational self-counseling and psychotherapy can be effective in helping a jilted person work through periods of distress and may help to reestablish emotional well being and good mental health. Counseling can assist the person in moving into new relationships, help the hurt person abandon dysfunctional behaviors and feelings, and aid the client in resuming a normal life. PMID- 2190255 TI - Investigating the impact of deconditioning anxiety on weight loss. AB - The effectiveness of a new model for the treatment of obesity was studied. This model assumed that obesity was not an eating disorder but a "not eating" disorder. Obese individuals do not have a problem eating, they are overly good at it. Obese individuals have a problem not eating. They experience difficulty or anxiety when they do not eat. The model assumed that removal of anxiety associated with "not eating" would allow obese subjects to lose weight. Wolpe and Lazarus' progressive relaxation techniques were used to decondition anxiety assumed associated with "not eating" in subjects. Inferred anxiety was deconditioned under conditions of "not eating" when imagining hunger, emotions, and cravings. Twenty-five subjects were instructed not to follow a diet after deconditioning but to eat less and be hungry to lose weight. A control group of 10 was instructed to follow a balanced 1000-calorie diet to lose weight. The former group lost a statistically significant amount of weight (7.5% of their body weight) over 11.9 months, while the control group subjects gained 6.5% of their weight. The model appears to be effective for the treatment of some individuals who wish to lose weight, based upon this preliminary study. Replication with other and larger groups is essential. PMID- 2190256 TI - Pharmacology of nootropics and metabolically active compounds in relation to their use in dementia. AB - The development of effective drugs for the treatment of dementia is an important therapeutic target. Drugs which stop the progression of dementia have not been developed; however, nootropics and metabolically active compounds such as the vinca alkaloids and the ergot alkaloids as well as alkylxanthines are widely used to alleviate the symptoms. This review summarises animal studies investigating the mechanism of action of these compounds and highlights gaps in our knowledge of their pharmacology. Nootropics, such as piracetam, facilitate learning and retrieval of information and protect the brain from physical and chemical intoxication. Nootropics may produce these effects via an enhancement of acetylcholine or dopamine release; however, this postulate requires further evaluation. The pharmacology of vinca alkaloids is reviewed with particular reference to vinpocetine. This compound attenuates cognitive deficits, reduces ischaemia-induced hippocampal cell loss and increases cerebral blood flow and glucose utilisation. These effects may be induced by modulation of cyclic nucleotide levels and adenosine re-uptake inhibition. An extensively examined ergot alkaloid is co-dergocrine; this compound increases both the oxygen tension and the electrical activity of the ischaemic cerebral cortex. Alkylxanthines have a wide range of pharmacological activities, and in this review the pharmacology of pentoxifylline, propentofylline and denbufylline is contrasted with that of theophylline and caffeine. In particular, the pharmacology of propentofylline and the selective low Km cyclic AMP phosphodiesterase inhibitor denbufylline is summarised. Although more carefully controlled clinical trials in well defined patient collectives are required, present evidence suggests some therapeutic efficacy for nootropics and metabolically active compounds. Further studies to more closely evaluate their mechanism of action may lead to the development of more effective agents for the therapy of dementia. PMID- 2190257 TI - Effects of morphine, ethylketocyclazocine, N-allylnormetazocine and naloxone on locomotor activity in the rabbit. AB - Locomotor activity was studied in the rabbit following injections of morphine, ethylketocyclazocine and N-allylnormetazocine. All three drugs produced only depression of activity. The opioid antagonist naloxone antagonized the effects of both morphine and ethylketocyclazocine. Naloxone (0.1 mg/kg) did not antagonize the effects of N-allylnormetazocine. Naloxone alone depressed locomotor activity at doses above 0.3 mg/kg. This effect of naloxone was partially antagonized by 0.1 mg/kg ethylketocyclazocine, but not by 0.1 mg/kg morphine. The GABA agonist muscimol (0.1 and 1.0 mg/kg) also did not antagonize the effect of naloxone on locomotor activity. Finally, amphetamine did not produce a great deal of locomotor activation in the rabbit, which may indicate that increasing activity in the rabbit by drug intervention may be inherently difficult. These results indicate that the opioids have effects in the rabbit that are clearly different from those observed in rodents, where morphine and N-allylnormetazocine have been reported to produce locomotor activation, and naloxone typically has little effect. In addition, the effects of the opioids on locomotor activity were clearly distinguishable from their effects on learning in the rabbit. While morphine and ethylketocyclazocine were approximately equipotent in depressing locomotor activity, morphine is much less potent than ethylketocyclazocine in retarding acquisition of the classically conditioned nictitating membrane response in the rabbit. PMID- 2190258 TI - [Pro-oxidant-induced proteolysis in the postradiation interphase death of thymocytes]. AB - Activity of intracellular alkaline proteinases increased and that of the trypsin like proteinase inhibitors decreased in thymocytes at early times following whole body X-irradiation of rats with a dose of 4 Gy. Pro-oxidant mechanisms of intracellular proteolysis activation are discussed. PMID- 2190259 TI - [The mechanisms of the action of radioprotectors of different chemical classes in the intestinal syndrome]. AB - Some thiazole, triazole, thiadiazine, and heterylalkane derivatives increased the lifespan of gamma-irradiated (9-14 Gy) mice up to 6-22 days (as opposed to 4.1 days in the irradiated control). The efficacy of chemical agents within the dose range mentioned above was mainly associated with protecting intestinal epithelium stem cells the number of which was 4-9 times as large as that of nontreated animals. There was a moderate (40-50%) decrease in oxygen consumption under the effect of the most active radioprotectors. PMID- 2190260 TI - [The effect of glycerine on gamma-induced mutagenesis in Salmonella typhimurium cells]. AB - A study was made of the modifying effect of glycerol on the survival rate and gamma radiation-induced mutagenesis of Salmonella typhimurium cells TA98, TA100 and TA102. The DMF value, with respect to the survival rate, was 2.05-0.20. The dependence of the yield of gamma radiation-induced mutants on radiation dose was described by the curve with a maximum; the mutation frequency M(D) was well described by a gradual function M(D) = kDx. DMF values of the induced mutagenesis amounted to 2 for strains TA100 and TA102, and 1.5 for strain TA98. PMID- 2190261 TI - [The significance of the cellular factor in realizing the restorative effect of the procedure of bone marrow exfusion, incubation and reimplantation in irradiated mice]. AB - In experiments with F1 (CBA X C57Bl) mice irradiated with doses of 6.5 to 8.5 Gy the evidence was obtained for the important role of the reimplanted cells in a complete realization of the reparative effect of exfusion, incubation and reimplantation of bone marrow. The increase in radiation dose was accompanied by a tendency towards the decrease in the efficacy of the procedure, and, perhaps, by changes in the ratio of roots of haemopoietic stem cell differentiation. PMID- 2190263 TI - [The effect on an impulse electromagnetic field on the bioamine allowance of the spinal ganglion in rats under whole-body exposure]. AB - In experiments with albino male rats subjected to whole-body pulse electromagnetic irradiation of 100 mTl magnetic induction, the luminescent histochemical methods and the subsequent microspectrofluorometry were used to determine the content of biogenic amines (catecholamines, serotonin, and histamine) in spinal ganglia neurons. Significant changes were revealed not only in the content of all studied bioamines but in the histamine/serotonin ratio as well. PMID- 2190262 TI - [The mechanism of the neuromotor disorders in the period of the primary reaction to irradiation]. AB - In experiments with dogs it was shown that the impairment of the capacity of fulfilling some actions (e. g. high jumping, equilibration, racing) was maximum 4h after gamma-irradiation with doses of 10 and 40 Gy and did not coincide with vomiting. By shielding body segments it was found that irradiation of abdomen was responsible for the disturbances observed. Novocaine blockade of innervation of abdomen prevented the impairment of the physical capacity, but not vomiting, during the first hours which was indicative of a major role of the reflex mechanism in motor disturbances genesis. PMID- 2190264 TI - Contextual diagnosis of Hodgkin's disease and non-Hodgkin's lymphoma. AB - The pathologic evaluation of microscopic slides from patients with possible HD or NHL must be performed in the context of complete chronology of the patient's history. Advances in flow cytometry (S-phase analysis), immunophenotyping, and molecular genetics may be of value in diagnosis, classification, and prognostication. The Rye modification of the Lukes-Butler classification of HD has been stable since 1966 and is widely accepted because of its proven reliability. By contrast, the proliferation of classifications of NHL since 1966 speaks for imperfection, partially due to the still incomplete understanding of this diverse group of lymphoreticular malignancies. Successive classifications have incorporated immunologic relationships and concepts and added a clinically significant grading system. A goal of the working formulation was to allow translatability between classifications in the interest of comparison and communication of clinical and research results. Knowledge of the patterns of involvement and spread by HD and by the different categories of NHL helps to narrow the differential diagnosis of radiologic findings. An awareness of the benign, reactive processes and nonlymphoreticular malignant neoplasms that mimic HD and NHL is essential to avoiding misdiagnosis. PMID- 2190265 TI - The radiologic assessment of the lymphoma patient from the standpoint of the clinician. AB - The characteristic radiologic and clinical features of the various types of lymphoma and Hodgkin's disease are discussed. In addition, the importance of the baseline radiologic evaluation of the patient with lymphoma as well as the process of restaging to assess response to therapy is detailed. PMID- 2190266 TI - Central nervous system lymphoma. AB - The imaging diagnosis of CNS lymphoma is challenging because of the multiplicity of compartments that it may present in or spread to, the variety of imaging manifestations that may be produced, and the fact that the clinical picture may not focus the clinician or radiologist on the correct diagnosis. However, recent strides in diagnostic imaging made not only with CT but now with MR allow recognition of tumor spread that was not possible before. Examples to support this statement are the noninvasive recognition of cord compression on MR, the demonstration of intraspinal and intracranial leptomeningeal tumor spread, and the improved demonstration of subdural tumor deposits. PMID- 2190267 TI - Lymphoma of the head and neck. AB - Lymphoma is the second most common neoplasm of the head and neck region and should be considered in the differential diagnosis of any lesion in this region, especially if the typical factors for squamous cell carcinoma are not present. The head and neck is the second most common site for extranodal lymphoma. It can involve virtually any region, including the orbit, paranasal sinuses, Waldeyer's ring, salivary glands, or thyroid. Communication with the surgeon and pathologist is essential to prevent an incorrect or delayed diagnosis. One should consider the diagnosis of lymphoma especially when multiple, large, nonnecrotic lymph nodes are present or multiple sites of disease are identified in extranodal tissue. PMID- 2190268 TI - Thoracic lymphoma. AB - Mediastinal adenopathy is a common manifestation of HD in a usually predictable pattern involving anterior and middle mediastinal nodes with or without disease in the hili. Hilar adenopathy is uncommon without detectable mediastinal disease and the lung is virtually never involved alone. In NHL the pattern of disease is more unpredictable. Lung manifestations include direct extension from involved nodes, nodules with or without cavitation, atelectasis secondary to endobronchial or nodal obstruction and rarely an interstitial pattern. Pleural effusions are not uncommon, but solid pleural masses are less frequent. Invasion of the pericardium is not often seen, although masses are commonly seen along the pericardium. Invasion of the chest wall occurs particularly with involvement of internal mammary nodes. Occasionally, posterior nodes will invade the adjacent vertebrae and spinal canal. The chest wall may be invaded by enlarged axillary nodes. Isolated chest wall soft-tissue masses are not common and are usually a manifestation of NHL, especially large cell lymphoma. Although the chest radiograph should detect most intrathoracic disease. CT has been found a necessary adjunct in patients with HD for accurate staging and therapy, especially if radiotherapy is planned. CT has been found helpful in NHL for staging, especially for the pleura and chest wall. MR imaging has not been found to contribute additional useful information except in selected cases. PMID- 2190269 TI - The treated thorax. AB - Significant progress has been made in the treatment of Hodgkin's disease and non Hodgkin's lymphoma. Responses to treatment may vary. Complications often occur. This article reviews the radiographic and clinical aspects of how the thorax responds to treatment. PMID- 2190270 TI - Lymphoma of the hollow abdominal viscera. AB - Autopsy evidence of gross or microscopic GI involvement can be found in up to 51% of all lymphoma cases. In descending order of frequency the stomach, small intestine, colorectum, and esophagus may be involved. Radiologically, GI lymphomas tend to have similar morphologic characteristics regardless of their site of origin. Additionally, the diverse radiologic manifestations may mimic a variety of diseases. Nevertheless, growing clinical experience and improvements in imaging techniques have increased the frequency with which the proper diagnosis can be suggested. The extramucosal origin of a mass or masses is often detectable by double-contrast examination and dictates a diagnostic spectrum fundamentally different from that of tumors arising from the mucous membrane. Similarly, the ability of CT to determine the wall thickness of the involved segment and its relationships to adjacent structures has further increased radiologic specificity. These capabilities are important, not only from the diagnostic standpoint, but also with respect to staging, prognosis, and, ultimately, increased survival. PMID- 2190272 TI - Diagnostic imaging of abdominal and pelvic lymph nodes in lymphoma. AB - Many diagnostic imaging techniques are available for the evaluation of the abdominal and pelvic lymph nodes in lymphoma. The merits and pitfalls of each are briefly described. The selection of any modality depends upon the type and extent of the disease. PMID- 2190271 TI - Lymphoma of the solid abdominal viscera. AB - Lymphomas of the solid abdominal viscera include hepatic (both primary and secondary), splenic, and pancreatic lymphomas. The use of the various diagnostic imaging modalities in each of these lymphomas is discussed, and the imaging appearance of each is described. PMID- 2190273 TI - Radiologic concepts of lymphoma of bone. AB - The imaging of lymphoma of bone is illustrated by conventional radiology, computed tomography, magnetic resonance imaging, and nuclear radiology. The features of non-Hodgkin's lymphoma are demonstrated. PMID- 2190274 TI - Lymphoma of the genitourinary tract. AB - Lymphomatous involvement of the genitourinary tract is extremely rare when it presents as primary extranodal disease. It is more common in the advanced stage of disseminated disease. Computed tomography is the best diagnostic modality to detect the involvement of the genitourinary tract. Although the appearances are generally nonspecific, certain characteristics on computed tomography may suggest and allow for a proper approach to the diagnosis. PMID- 2190275 TI - Lymphoma in the immunocompromised patient. AB - The increased incidence of malignant lymphomas in patients with congenital or acquired immunodeficiency states is now well recognized. In recent years, acquired immunodeficiency syndrome (AIDS) related non-Hodgkin's lymphoma has accounted for a growing proportion of these aggressive neoplasms. This article reviews the radiographic features of lymphoma in AIDS and non-AIDS immunocompromised patients. PMID- 2190276 TI - The natural history of diabetic nephropathy. AB - Diabetic nephropathy is now the most common cause of ESRD in the US, and no other complication of diabetes is associated with more deaths. In addition to its impact on morbidity and mortality, it extracts a tremendous cost from the health care economy. Prevention and better treatment of diabetic renal disease should be a high priority for both the health-care system and society at large. Ultimately, diabetic nephropathy should be preventable, but that goal can be accomplished only by the coordinated efforts between investigators, who work to uncover pathophysiologic processes and design new treatments, and clinicians, who take those findings to the patient's bedside. PMID- 2190277 TI - Mechanisms of proteinuria in diabetic renal disease. PMID- 2190278 TI - Tubular function in diabetes mellitus. PMID- 2190279 TI - Pathogenesis of diabetic glomerulopathy: hemodynamic considerations. PMID- 2190280 TI - Hyperfiltration and diabetic nephropathy: is it the beginning? Or is it the end? AB - At present the pathogenesis of diabetic nephropathy remains unresolved. Clearly lack of insulin, with its associated disorders of carbohydrate, protein, and/or lipid metabolism, initiates the process which eventually leads to the characteristic histologic picture of diabetic nephropathy. The disturbance in cellular metabolism per se could directly injure the kidney by altering the energy needs of the cell or by leading to the accumulation of cellular toxins (ie, polyols) or by causing the deficiency of key cellular metabolites (ie, myoinositol). Elevation of the plasma glucose concentration enhances the glycosylation of proteins, which in turn can lead to glomerular basement membrane thickening, loss of charge selectivity, and direct cellular damage. The multiple disturbances in intermediary metabolism are associated with increased levels of and/or enhanced sensitivity to a variety of growth factors, including IGF-I and angiotensin, and this could lead to glomerular hypertrophy. An increase in the filtered load and subsequent reabsorption of electrolytes and metabolites also could contribute to renal hypertrophy. In all animal models of nephropathy, including diabetes, glomerular hypertrophy has been shown to be the best correlate of glomerular sclerosis, proteinuria, and progressive renal deterioration. The potential mechanisms by which glomerular hypertrophy can lead to renal histologic damage were discussed previously. By increasing the luminal diameter, glomerular hypertrophy also would be expected to augment wall tension and thereby increase intraglomerular pressure. Derangements in cellular metabolism or altered sensitivity to angiotensin also can directly elevate the intraglomerular pressure and lead to structural renal damage. In this schema, elevated intraglomerular pressure is but one of many pathogenic factors that contribute to the development of diabetic glomerulopathy and albuminuria. The precise role of increased glomerular pressure in the evolution of diabetic nephropathy remains uncertain at present. In rats, severe diabetic nephropathy can occur without an increase in Pgc, while in humans, hyperfiltration does not appear to be a predictor of proteinuria and renal dysfunction. Lastly, it is likely that a variety of other factors, including the coagulation system, plasma/cell lipid levels, prostaglandins, etc, also play a role in the pathogenesis of diabetic nephropathy. According to the outline presented in Figure 1, it is unlikely that any single factor will be sufficient to explain the development of diabetic glomerulosclerosis. Ultimately, the origin of diabetic nephropathy in IDDM must be traced to insulin lack, with its associated derangements in cellular metabolism. Therefore, the importance of tight glucose control should not be underemphasized.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2190281 TI - Renal hypertrophy, growth factors, and nephropathy in diabetes mellitus. AB - In early type 1 diabetes mellitus, hypertrophy of the kidney is a consistent finding. It is easily diagnosed using current noninvasive methods, especially ultrasonography. Renal functional changes occur in association with hypertrophy, most notably glomerular hyperfiltration. The structural counterpart of this functional change is an early increase in capillary filtration surface area. In most forms of nondiabetic renal hypertrophy, kidney size is closely linked to GFR, but in diabetes, hypertrophy persists after the clinical onset of overt kidney disease (microalbuminuria, hypertension, decreased GFR, etc). The fact that growth factors produced by the kidney can act in both an autocrine and paracrine fashion raises the possibility that the local effects of such substances may act as local mediators of kidney growth, but no such factor has been identified as the initiating or sustaining factor in diabetic hypertrophy. Failure of renal hypertrophy to reverse following strict glycemic control for a few months may turn out to be an important prognostic indicator of future progression of the renal disease, but this remains to be studied in a large group of patients. PMID- 2190282 TI - Renal histologic changes in diabetes mellitus. PMID- 2190283 TI - Prevention and treatment of renal disease in insulin-dependent diabetes mellitus. PMID- 2190284 TI - Care of the diabetic patient with end-stage renal disease. AB - Diabetic nephropathy is now the leading cause of renal failure in patients referred for uremia therapy. The diabetic patient is a complicated treatment problem from the first detection of microalbuminmuria, at which time decisions regarding choice of antihypertensive and strictness of metabolic control assume increasing importance. At present, our policy is to advocate strict control of blood pressure, aiming for a systolic blood pressure of less than 140 mm Hg and a diastolic blood pressure of less than 80 mm Hg. We attempt to maintain hemoglobin Alc levels at less than 8%, if the patient does not develop frequent episodes of hypoglycemia. We extend these recommendations to the patient with frank proteinuria, nephrotic syndrome and early uremia, understanding that strict metabolic control may be impossible as patients lose GFR. In addition, we recommend avoidance of a high protein diet in the early nephropathic diabetic, with diet of approximately 1 gm/kg/d. As renal failure progresses, we embark on an analysis of the patient's abilities, lifestyle, and social support. At a GFR of approximately 10 mL/min, we initiate preparations for uremia therapy. If a willing and appropriate living related kidney donor is available, the patient is referred for cardiovascular evaluation and kidney transplantation performed subsequently. If no donor is immediately available, we refer the patient for vascular access placement and/or insertion of a Tenckhoff peritoneal catheter, if preferred. Most of these predialysis patients also undergo screening for placement on the cadaveric kidney transplant list, including cardiac work-up as is done for the patients who receive living-related renal transplants. Because of the long waiting list in Brooklyn, and the universal shortage of organ donors, many of these patients eventually end up on dialysis for some period of time. Other extrarenal problems (urologic, ophthalmologic) are addressed at initial referral and followed up, in hopes of maintaining the patient in optimal physical shape as uremia progresses. The care of the diabetic patient with ESRD ideally involves a consortium of caregivers. We include a nurse-educator familiar with options for uremia therapy, a podiatrist, a cardiologist, and often a urologist, an endocrinologist, and a gastroenterologist. In addition, a social worker is helpful to assess psychologic difficulties in adjustment to uremia, socioeconomic considerations, and rehabilitation status. Finally, the nephrologist, as coordinator of this team works with the vascular or transplant surgeon, to facilitate the transition to ESRD and its therapy. PMID- 2190285 TI - Low protein diets and diabetic nephropathy. PMID- 2190286 TI - Are glomerular hypertension and "hypertrophy" independent risk factors for progression of renal disease? PMID- 2190288 TI - Latent class analysis of diagnostic agreement. AB - We describe methods based on latent class analysis for analysis and interpretation of agreement on dichotomous diagnostic ratings. This approach formulates agreement in terms of parameters directly related to diagnostic accuracy and leads to many practical applications, such as estimation of the accuracy of individual ratings and the extent to which accuracy may improve with multiple opinions. We describe refinements in the estimation of parameters for varying panel designs, and apply latent class methods successfully to examples of medical agreement data that include data previously found to be poorly fitted by two-class models. Latent class techniques provide a powerful and flexible set of tools to analyse diagnostic agreement and one should consider them routinely in the analysis of such data. PMID- 2190287 TI - Estimating the distribution of times from HIV seroconversion to AIDS using multiple imputation. Multicentre AIDS Cohort Study. AB - Multiple imputation is a model based technique for handling missing data problems. In this application we use the technique to estimate the distribution of times from HIV seroconversion to AIDS diagnosis with data from a cohort study of 4954 homosexual men with 4 years of follow-up. In this example the missing data are the dates of diagnosis with AIDS. The imputation procedure is performed in two stages. In the first stage, we estimate the residual AIDS-free time distribution as a function of covariates measured on the study participants with data provided by the participants who were seropositive at study entry. Specifically, we assume the residual AIDS-free times follow a log-normal regression model that depends on the covariates measured at enrolment on the seropositive participants. In the second stage we impute the date of AIDS diagnosis for the participants who seroconverted during the course of the study and are AIDS-free with use of the log-normal distribution estimated in the first stage and the covariates from each seroconverter's latest visit. The estimated proportions developing AIDS within 4 and within 7 years of seroconversion are 15 and 36 per cent respectively, with associated 95 per cent confidence intervals of (10, 21) and (26, 47) per cent. We discuss the Bayesian foundations of the multiple imputation technique and the statistical and scientific assumptions. PMID- 2190289 TI - Covariance analysis in generalized linear measurement error models. PMID- 2190290 TI - [Sleep disturbances from the internist's viewpoint]. AB - Sleep disorders are common and can be caused by somatic diseases. Chronic pain as well as heart and lung conditions are able to interfere with the normal sleep pattern. Obstructive sleep apnea is caused by a deranged central control of breathing occurring during sleep and leads to a sleep-fragmentation and consequently to daytime hypersomnolence. A problem oriented meticulous history can give valuable insights and distinct diagnostic considerations form the basis for an eventually successful therapeutic approach. Polysomnography is done in particularly puzzling cases and for evaluation of invasive therapeutic measures. PMID- 2190291 TI - [Homeopathy]. AB - Homeopathy has been disputed from the early beginning. The rational basis of homeopathy neither can be established by philosophy nor by natural sciences. On one hand homeopathy is supported by so-called 'empirical physicians', but on the other hand it is usually heavily criticized by physicians who are basing their criticism on natural sciences. 'Healing' is meant to prove the hypothesis of all paramedical people, it can however be easily explained on a rational basis. It is indisputable that paramedical manipulations not only may act by placebo effect but also can appear successful due to the remarkable power of our body for self healing. If latter plays an important role, especially when there is no time limit for healing. We never tried to convince paramedical ideologists, who are already heavily engaged in paramedical treatment, but it is our aim to reassure with solid arguments colleagues, who have so far been overwhelmed by irrational journalism. PMID- 2190292 TI - [Assessment of the course of chronic polyarthritis]. AB - In the following review the classical clinical and radiological parameters of rheumatoid arthritis are discussed. In our own study we made a prospective follow up of 29 patients with rheumatoid arthritis (104 years of disease) comparing the clinical and laboratory data with the radiological findings. Finally we investigated in another population with rheumatoid arthritis (315 patients) the question of quality of life using a structured questionnaire. PMID- 2190293 TI - [Arterial hypertension and oral contraceptives]. PMID- 2190294 TI - [Arterial hypertension and obesity]. AB - Overweight and arterial hypertension have been found to be associated in most studies in diverse populations. Several possible mechanisms for this association have been proposed: hemodynamic modifications, glucose and lipid metabolism alterations, hyperinsulinemia, neuroendocrine abnormalities. However, it seems difficult to explain the relation obesity-hypertension by a single mechanism. The search for a physiopathological explanation including the diverse abnormalities found in obese hypertensive subjects must go on. PMID- 2190295 TI - [Tuberculosis therapy 1990]. AB - The goal of modern therapy of tuberculosis is the rapid killing of all bacilli with potent and relatively atoxic antituberculous drugs. Currently available first-line drug regimens are highly effective, well tolerated and relatively easily administered. The addition of Pyrazinamide enables the minimum treatment period to be shortened to six months (two months Isoniazid, Rifampin, Pyrazinamide and four months Isoniazid, Rifampicin). This article reviews the available first-line drugs in treatment of tuberculosis, the rationale for the recommended chemotherapeutic regimens, the follow-up of treated patients and special issues related to the treatment of extrapulmonary tuberculosis and tuberculosis in HIV-infected patients. PMID- 2190296 TI - [Motility of the bronchi]. AB - Airway diameter depends on bronchial smooth muscle tone which is regulated via complex nervous influences including afferent and efferent vagal fibers, sympathetic agonists and the so called 'third nervous system' (non adrenergic non cholinergic), as recently described. Additionally, various mediators of inflammation and epithelium derived factors contribute to the regulation of bronchi motility in health and disease. PMID- 2190298 TI - [Vilem Laufenberger 1890-1986 (on the 100th anniversary of his birth)]. PMID- 2190297 TI - [The xanthines: status in the therapeutic arsenal in 1990]. AB - Methylxanthines are at present widely prescribed for obstructive airway-diseases. However, the exact therapeutic role of these drugs is not clear in 1990. In this short review, we discuss what we think to be a rational use of xanthines in asthma and in COPD patients: shortly speaking, we propose that the drugs are not first-line therapeutic tools and should be only prescribed in selected situations. PMID- 2190299 TI - [A remembrance of Academician Vilem Laufenberg]. PMID- 2190300 TI - Non-specific cleavage of collagen by proteinases in the presence of sodium dodecyl sulfate. AB - Proteolytic degradation of collagen normally requires specific collagenases of either mammalian or microbial origin. We have observed, among many detergents, a unique effect of sodium dodecyl (= lauryl) sulfate after preincubation of insoluble collagen (type I) with detergent. When treated fibrils were isolated and resuspended in detergent-free buffer, they were very sensitive to cleavage by non-specific proteases like trypsin, elastase, and subtilisin. We suggest that dodecyl sulfate causes a structural change in the collagen molecule which abrogates the resistance of collagen to most proteolytic enzymes. These observations may have implications for collagen and connective tissue research in general and especially to periodontal research. Lauryl sulfate (2-5%) is included in the majority of toothpaste formulations as a foaming agent, and our results again raise the question whether toothbrushing with lauryl sulfate may accelerate periodontal destruction by synergism with bacterial and host proteases. It may also bind to the collagen in exposed root surfaces and thus affect the stability of their hard tissues. PMID- 2190301 TI - Occurrence of malocclusion in attritive environment: a study of a skull sample from southwest Finland. AB - Occlusal variation and occurrence of malocclusion were examined in a Finnish skull sample derived from the 15th and 16th centuries. The material consisted of 207 adult individuals; 141 maxillas and 159 mandibles, including 93 pairs, were in observable condition. In the skull sample, only dental anomalies were observed; no skeletal malocclusions were found. The frequency of an Angle Class I lateral relationship was 97.7%. The mean values for overjet and overbite were 1.6 and 1.4 mm, respectively. A comparison with present-day Finns revealed that the skull sample showed less variation in all occlusal variables studied. An Angle Class II type occlusion, deep bite, crowding, spacing, and lateral crossbite occurred with significantly lower frequencies in the skull sample than in the present-day Finns. Advanced dental wear in the skull sample shows that a hard and attritive diet was eaten at that time. It is suggested that a dietary transition from hard to soft food is the most probable cause of the increased occlusal variation and high frequency of malocclusion in present-day Finns. PMID- 2190302 TI - Strength of bond with Comspan Opaque to three silicoated alloys and titanium. AB - In Sweden high-gold alloys or cobalt-chromium alloys are used for resin-bonded prostheses. The bond strength between a resin cement and different sandblasted or silicoated metals were measured before and after thermocycling; in connection with this some rapid thermocycling methods were studied. The effect of different storage times and different protection coatings on bond strength were tested. Finally, the influence of rubbing and contamination with saliva on bond strength were investigated. Silicoating increased the bond strength significantly. The highest bond strengths were these of silicoated Wirobond and titanium, unsusceptible to thermal stress; the bond strengths of the sandblasted metals were the weakest, and sensitive to thermocycling as well. The influence on bond strength for silicoated gold alloys, protected with an unpolymerized composite resin coating, stored in sealed plastic bags up to 7 days, was negligible. Rubbing and contamination with saliva did not influence bond strength. Preferably, silicoated Wirobond and titanium should be used for resin-bonded prostheses, but gold alloys may still be adequate for clinical use. The experimental method described for storing, sealing, and cleaning the silicoated metal surfaces in this article can be recommended for laboratory and clinical use. PMID- 2190303 TI - Effect of casting atmosphere on the quality of Ti-crowns. AB - Ti has a strong affinity to elements like O, N, and C. During melting a non reacting crucible and vacuum and/or Ar-gas protection therefore have to be used. If the impurity content becomes too high, the material turns hard and brittle. In the present work vacuum/Ar-pressure casting of crowns has been carried out at different air pressure levels. Recording of hardness on cross-sections of the castings and the degree of mold filling show that an air pressure level less than 1 torr in the melting chamber and less than 10 torr in the mold chamber is sufficient to obtain sound castings of a small size like a crown. PMID- 2190304 TI - The protective and therapeutic mechanisms of sucralfate. AB - Sucralfate is a nonsystemic agent that is effective in protecting the gastroduodenal mucosa against injury. In addition, sucralfate is effective in the healing of acute duodenal and gastric ulceration, the therapy of esophagitis, and the prevention of ulcer recurrence. The mechanisms responsible for sucralfate's successful protective and therapeutic actions include the adsorption of pepsin and bile acids, the stimulation of bicarbonate and mucus secretion, and stimulation of endogenous synthesis of prostaglandins. When sucralfate is given to experimental animals or humans, it stimulates endogenous synthesis and release of prostaglandin E2 and inhibits thromboxane release. Pretreatment of animals with the cyclooxygenase inhibitor indomethacin results in a marked decrease in the protective effect of sucralfate against alcohol injury. Sucralfate also increases epidermal growth factor binding to ulcerated areas and stimulates macrophage activity. In addition, sucralfate stimulates endogenous sulfhydryl compounds. At the microscopic level sucralfate protects the vascular integrity of the mucosa and the mucosal proliferative zone. It also stimulates epithelial cell restitution and stimulates cell proliferation. The administration of sucralfate before acute injury results in decreased depth and extent of injury and in acceleration of healing. Because of sucralfate's ability to stimulate the protective and reparative mechanisms of the gastric and duodenal mucosa, it is an important nonsystemic agent for the therapy and prevention of peptic ulceration. PMID- 2190305 TI - Future potential applicability of sucralfate in gastroenterology. AB - Sucralfate plays an important role in peptic ulcer disease, reflux esophagitis, stress erosions and bleeding, and as adjunctive therapy in variceal sclerosis. In accordance with its pharmacologic characteristics, however, one may readily envisage disease states worth investigating, such as irradiation-induced mucosal damage of the esophagus. Especially the combination of external and intraluminal radiotherapy via the after-load technique may cause substantial and occasionally long-standing ulceration of the esophageal lining and discomfort. Several conditions of the stomach deserve further study. Increasingly common is gastric mucosal damage induced by aspirin or non-steroidal anti-inflammatory drugs. On the basis of its various pharmacologic principles sucralfate should theoretically offer protection against such lesions, and, in fact, there are human pharmacologic and clinical studies available supporting this idea. Another disease entity in which sucralfate should be studied in more depth is that of biliary alkaline reflux gastropathy as often seen after gastric surgery. Sucralfate should also be evaluated in those difficult clinical conditions known to be resistant to any therapeutic attempt with currently available drugs, such as erosive varioliform gastritis and hypertrophic gastropathy with heavy inflammation of the mucosa and giant coarsening of the gastric rugae. The results obtained with sucralfate in variceal sclerosis are indeed intriguing, even though the mechanism is not understood. It has been shown that sucralfate has some efficacy in patients with hemorrhagic gastritis. In many patients receiving chemotherapy, mucosal damage may occur both in the mouth and throughout the gastrointestinal tract, including the small bowel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190306 TI - Why do ulcers heal with sucralfate? AB - It is unknown why ulcers in general heal. Some clues are worth considering. What is known is (i) that ulcer healing occurs spontaneously, (ii) that ulcers heal more quickly in the duodenum than in the stomach, (iii) that mucosal blood flow at ulcer edge improves with healing, and (iv) that healing can be speeded up by (a) not smoking, (b) removing acid from the stomach, and (c) using non antisecretory mucosal protective agents such as sucralfate and colloidal bismuth. The difference in healing rates between duodenal and gastric ulcers may be related to ulcer size, duodenal alkalinity due to the secretion of the Brunner's glands, and other uninvestigated factors such as epidermal growth factor and mucosal blood flow. The difference between smokers and non-smokers may be related to inhibition of prostaglandin synthesis and impairment of mucosal blood flow due to smoking and to higher acid secretion in smokers. The success with antisecretory agents indicates that acid inhibits the healing process. The success of sucralfate and bismuth indicates that cytoprotective mechanisms play a role in ulcer healing. The literature also shows that ulcer healing is less affected by smoking in patients treated with sucralfate than in those treated with antisecretory agents, suggesting that cytoprotective mechanisms play a more important part than acid inhibition in counteracting the adverse effects of smoking on healing. Furthermore, ulcer relapse occurs sooner in patients treated with antisecretory agents than in those treated with sucralfate or bismuth, suggesting that withdrawal of antisecretory agents speeds up relapse and/or that cytoprotective mechanisms are associated with longer-lasting remission. It is concluded that sucralfate healing involves cytoprotective mechanisms and that these cannot be ignored in the planning of any anti-ulcer therapy. Despite the understanding of the various site-protective and cytoprotective mechanisms, as discussed in the previous article, it is not clear why ulcers heal with sucralfate. In fact, there is no clear answer to the fundamental question as to why ulcers in general heal with the known therapeutic agents, including H2 receptor antagonists, antacids, proton pump inhibitors, anticholinergics, site protective agents, and cytoprotective agents. This review examines this question, using sucralfate as a model. PMID- 2190307 TI - [Limitations to the preservation of continence in rectal carcinoma]. AB - Several reports have documented favorable results for abdominal rectal resection with coloanal anastomosis for adenocarcinoma of the rectum, though selection and the low number of patients make it difficult to compare the new restorative procedures with abdominoperineal excision. In a personal series of 35 patients treated by abdomino-transsphincteric and abdominotransanal resection, operative mortality was 2.9% and the incidence of clinically relevant pelvic sepsis was 19%. Results with respect to local control were satisfactory: in Dukes stage C (n = 12) and D (n = 4) tumors, followed up for 6 months to 9 years (mean 2.7 years), the incidence of pelvic recurrence was 19%. 3 pelvic recurrences with Dukes stage A (n = 13) or B (n = 6) tumors were observed, possibly related to operative rectal perforation in one instance and to a narrow safety margin in another patient. From this experience, and from surgical anorectal anatomy demonstrating fusion between the visceral and the somatic tube at 5 cm from the anal verge, it is concluded that proctectomy with coloanal anastomosis is a safe procedure for mid-rectum adenocarcinoma, but that a majority of low-lying cancers (greater than or equal to 6 cm ab ano) must be treated by abdominoperineal excision. PMID- 2190308 TI - [Does Barrett's esophagus regress after effective treatment of gastro-esophageal reflux?]. AB - Regression and disappearance of Barrett's esophagus are a rare event of which there are only three well documented cases in the literature. Two cases are described in this study. PMID- 2190309 TI - [Diagnostic DNA probes]. AB - Advances in molecular biology have had a tremendous impact on our understanding of the pathogenesis of hereditary disorders, tumours and infectious diseases. It is anticipated that recombinant DNA technology will gradually assume an important role as a diagnostic tool in medicine, since at least some of the techniques are now ready for routine use in the clinical laboratory. The most lucrative application (and hence the most competitive market) for DNA probes will be the detection of bacteria, viruses and other microbiological organisms by nucleic acid hybridization techniques. The value of recombinant DNA technology for prenatal diagnosis and carrier detection in genetic disorders is now firmly established. Analysis of DNA and RNA obtained from tumours may provide diagnostic information of practical relevance in carefully selected cases. It is, however, unlikely to challenge the established value of the more "traditional" diagnostic tools such as histopathology and immunophenotyping. PMID- 2190310 TI - [DF-2, a "new" gram-negative bacterium]. AB - Dysgonic fermenter 2 (DF-2) is a long, fastidious gram negative rod that leads to life-threatening infections in immunocompromised and especially splenectomized patients. It can also severely affect the healthy individual. It is mainly acquired through contact with dogs and after dog bites. The infection has rarely been described, due to difficulties in isolating DF-2, its relatively low virulence, its susceptibility to antimicrobial agents and the frequent administration of antibiotics after animal bites. A systematic approach to the practical management of dog bite wounds is proposed. PMID- 2190311 TI - [Respiration physical therapy?]. AB - This review assesses the role of physical modalities - chest physical therapy, breathing exercises, breathing training, and physical exercises - in the treatment of patients with pulmonary diseases. Controlled studies suggest that "routine" exercises yield a disappointing effort-benefit ratio, but that individually adapted programs may improve the well-being and functional ability of selected patients. PMID- 2190312 TI - [When does snoring need assessment?]. AB - Snoring and obstructive sleep apnea (OSA) are both related to narrowing of the upper airways during sleep. However, because the sex ratios of snoring and OSA are very different, snoring cannot simply be regarded as a preapneic state. Symptoms of OSA, a potentially life-threatening disorder, include excessive daytime sleepiness, nocturnal breath cessation and snoring and gasping. Most patients are obese, hypertensive men who eventually develop cardiovascular abnormalities. Snoring patients only need sleep laboratory evaluation if OSA is suspected based on clinical information. PMID- 2190313 TI - [Cyclosporin in autoimmune diseases]. AB - The efficacy of cyclosporine (Sandimmun) is well established in the field of organ transplantation. More recently, prospective controlled trials were performed in patients with other diseases. The efficacy of cyclosporine for the following clinical entities was proven by the trials: endogenous uveitis, rheumatoid arthritis, Sjogren's syndrome, myasthenia gravis, psoriasis and Crohn's disease. Furthermore, there is evidence from a controlled trial of some benefit for patients with aplastic anemia. The proteinuria of patients with glomerulonephritis was reduced by cyclosporine, though no improvement in glomerular filtration rate was observed. Large controlled trials in patients with multiple sclerosis or amyotrophic lateral sclerosis revealed a beneficial effect on some clinical parameters. Nevertheless, cyclosporine cannot be recommended for these patients at the present time, since the ratio between the (slight) beneficial effects and the side effects was unfavourable. In patients with primary biliary cirrhosis, cholestasis slightly diminished after the administration of cyclosporine. Whether this improvement in laboratory parameters predicts an improved outcome in patients with primary biliary cirrhosis has yet to be demonstrated. Some patients with recently diagnosed insulin dependent diabetes needed no further insulin therapy as long as cyclosporine was administered. This is an observation of tremendous potential practical relevance for the future, when methodology may be available for diagnosing autoimmune destruction of beta-cells before clinically overt diabetes is present. Cyclosporine combined with prednisone was slightly more efficacious in patients with Graves' ophthalmopathy than prednisone alone. For all other autoimmune diseases, no controlled studies with cyclosporine are available at the present time. The most important side effects of cyclosporine are renal dysfunction, hypertension, gout, tremor, gingival hyperplasia and hypertrichosis. These side effects are manageable by appropriate dosage of cyclosporine and prophylactic measures. Side effects caused interruption of cyclosporine therapy in less than 5% of the patients. Thus, cyclosporine appears to be an efficacious new agent for treatment of some groups of patient with immune diseases. PMID- 2190314 TI - NSF education chief lost in the shuffle. PMID- 2190315 TI - Induction of CD4+ human cytolytic T cells specific for HIV-infected cells by a gp160 subunit vaccine. AB - Cytolytic T lymphocyte (CTL) responses were evaluated in humans immunized with recombinant human immunodeficiency virus type 1 (HIV) envelope glycoprotein gp160. Some vaccinees had gp160-specific CTLs that were shown by cloning to be CD4+. Although induced by exogenous antigen, most gp160-specific CTL clones also recognized gp160 synthesized endogenously in target cells. These clones lysed autologous CD4+ T lymphoblasts infected with HIV. Of particular interest were certain vaccine-induced clones that lysed HIV-infected cells, recognized gp160 from diverse HIV isolates, and did not participate in "innocent bystander" killing of noninfected CD4+ T cells that had bound gp120. PMID- 2190316 TI - Studies of the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one in thalassemia patients. PMID- 2190317 TI - Pyridoxal isonicotinoyl hydrazone: an effective iron-chelator after oral administration. PMID- 2190319 TI - The genetics of glucose-6-phosphate dehydrogenase deficiency. AB - In the past 35 years, G-6-PD and its genetic variants have been a valuable resource for the geneticist and cell biologist. Over 380 putative variants have been described and have served as a paradigm, showing how many ways mutations can affect an enzyme. With the cloning and sequencing of G-6-PD, a new chapter has been opened in our understanding of G-6-PD. Variants that were thought to be different have proven to be identical, and those that were thought to be the same are now seen to be heterogeneous. Importantly, the ability to deduce quickly the amino acid substitution in a G-6-PD variant makes feasible, for the first time, the unraveling of relationships between the structure and function of this enzyme. PMID- 2190318 TI - Recurring chromosome abnormalities in leukemia and lymphoma. PMID- 2190320 TI - Oral iron chelators. PMID- 2190321 TI - Current status of iron chelation therapy with deferoxamine. AB - Long-term chelation therapy with deferoxamine is an effective and generally safe method for removing excessive iron, preventing iron-induced organ damage and improving survival of patients with transfusion-dependent disorders. The current treatment of iron overload is an important standard against which new forms of therapy, such as oral chelators, should be measured to ensure that their risks and benefits compare favorably with deferoxamine. Until new treatments are available, continuing studies of deferoxamine will help to define its long-term efficacy and toxicity for patients with thalassemia major and other hematologic disorders. PMID- 2190322 TI - Principles of iron chelating therapy. PMID- 2190323 TI - Update on the hydroxypyridinone oral iron-chelating agents. PMID- 2190324 TI - Adult supratentorial tumors. AB - MR imaging has represented a significant advance in the diagnosis and management of adult supratentorial neoplasms, and indeed MR has become the modality of choice for the initial diagnosis and follow-up in these cases. It is clear that the overall sensitivity has increased significantly, due to both the use of MR itself and to the implementation of IV contrast agents. It appears that some inroads have been made with regard to specificity, but significant overlap still exists in the imaging appearance of many of these entities. A thorough knowledge of neuroanatomy, pathophysiology, and neuropathology aid markedly in the imaging diagnosis of these processes. PMID- 2190325 TI - Imaging of intrasellar, suprasellar, and parasellar tumors. AB - The complex anatomy and multiple functions of the structures involved in the sella, suprasellar, and parasellar spaces present a challenge for the imager in identifying an etiology when symptoms are present. Computed tomography, magnetic resonance imaging, and arteriography all play roles depending upon the localization of the process. In this area, as in others, care must be exercised, as nonneoplastic masses may mimic those that are neoplasms. Studies must be tailored to answering questions posed by the differential diagnosis. PMID- 2190326 TI - [Preliminary studies on the relationship between the blood pressure and renin angiotensin system in brain and blood vessels in SHRSP]. AB - This work analyzed the relationship between A I concentration in aorta tissue and systolic blood pressure (SBP) in stroke-prone spontaneously hypertensive rats (SHRSP) at different ages. The SBP of SHRSP increased progressively with the age until the age of 20 weeks, when the SBP of SHRSP no longer elevated but sustained at a relatively high and stable level. The A I concentration in aorta of SHRSP was much higher than that of Wistar Kyoto rats at all of the three different ages. Perfusion of captopril into the lateral cerebroventricle of SHRSP for four weeks evoked a considerable decrease of A I concentration in brain as well as a significant reduction of SBP accompanied by a decrement of A I concentration in aorta and concentration of norepinephrine and epinephrine in aorta tissue and plasma. The results further confirm the close relationship between the changed activity of renin-angiotensin system localized in blood vessels during hypertension and the pathogenesis of hypertension, and indicate the possible regulative control of A I generated from central nervous system over the production of A I from blood vessels by means of facilitating the activity of peripheral sympathetic nerve system. PMID- 2190327 TI - [Continuous perfusion of dispersed anterior pituitary cells: a model for LHRH regulation of LH secretion]. AB - The anterior pituitary (AP) tissues were removed from adult male Sprague-Dawley rats by decapitation. The dispersed cells with high viability (greater than or equal to 95%) were prepared using trypsin digestion and mechanical dissociation, and then mixed with Bio-Gel P2, packed into the columns, and perfused continuously with M199 medium for more than 24 hours. Different doses of LHRH were administered by 6-min pulses at one hour intervals. A steady and detectable basal LH secretion was present in all columns during the experiment. LHRH stimulation pulse could induce LH secretion rapidly, and repeated LHRH pulses of same dose produced statistically equal LH pulses. The dose-response curve of LH secretion was linear within the range of 1 X 10(-10) to 1 X 10(-7) mol/L LHRH. These results indicate that continuous perfusion system of dispersed AP cells which offers significant advantages over other methodologies provides a very useful in vitro model for studying the mechanisms on LHRH regulation of LH secretion. PMID- 2190328 TI - Case managers for the mentally ill. PMID- 2190329 TI - [Use of sermion, Cavinton and trental in patients with cerebrovascular disorders]. PMID- 2190330 TI - Initial evaluation of the patient with blunt abdominal trauma. AB - Unrecognized abdominal injury remains a distressingly frequent cause of preventable death following blunt trauma. Peritoneal signs are often subtle, overshadowed by pain from associated injury, and masked by head trauma or intoxicants. The initial management of the patient with blunt abdominal trauma should parallel the primary survey of airway, breathing, and circulation. Diagnostic peritoneal lavage remains the cornerstone of triage in patients with life-threatening blunt abdominal trauma. The only absolute contraindication to the procedure is an existing indication for laparotomy. Computed tomography is useful as a complementary diagnostic tool in selected patients, and it is the critical test for guiding nonoperative management of known intraperitoneal trauma. Routine ancillary tests for potentially occult injuries include nasogastric-tube placement for ruptures of the left diaphragm, Gastrografin contrast study for duodenum perforation, and pyelography for urologic injury. Ultrasonography may become a valuable tool in the initial assessment of the injured abdomen. Ultimately, the most important principle in the management of blunt abdominal trauma is repeat physical examination by an experienced surgeon. PMID- 2190331 TI - Management of gastric injuries. AB - The stomach, located in the intrathoracic portion of the abdomen, is well protected from injury. It has a thick wall that is easily mobilized and a rich blood supply that ensures rapid healing of wounds. Although the gastric contents may be contaminated by oral flora immediately after meals, in the resting state, the stomach has few, if any, endogenous organisms. All of these factors make morbidity and mortality associated with penetrating injuries low. In contrast, blunt injuries often cause extensive contamination of the peritoneal cavity with resultant high morbidity and mortality. PMID- 2190332 TI - Duodenal injuries. AB - The lethal potential of duodenal trauma relates to the severity of the defect, associated injuries, expedient diagnosis, and adequacy of repair. A high index of suspicion must be used in patients sustaining blunt abdominal trauma. An aggressive approach to penetrating abdominal trauma will detect the majority of duodenal injuries in a timely fashion. The unique anatomic and physiologic characteristics of the duodenum demand careful selection of the operative repair to fit the injury. A classification scheme is reviewed that should help the surgeon select the appropriate procedure from a multitude of choices. Standard postoperative care is required. Adherence to these principles should result in acceptable morbidity and mortality in patients with duodenal injuries. PMID- 2190333 TI - Small bowel injuries. AB - Small bowel injuries are becoming more commonplace. Difficult to diagnose and treacherous when missed, small bowel injuries should be searched for assiduously in all patients at risk. Use of DPL or CT scanning, coupled with a low threshold for exploration, improves the diagnosis and treatment of small bowel injuries. A delayed diagnosis results in a progressive septic insult and markedly increased mortality. Early diagnosis is the key. After addressing life-threatening problems, the operation should include a thorough and systematic exploration to identify all injuries. Sound surgical technique includes debridement of nonviable tissue, restoration of small bowel continuity, generous irrigation, and placement of enteral feeding catheters. By adhering to the preceding principles and by exercising meticulous postoperative care and maintaining a low threshold to reoperate, catastrophic complications can be avoided. PMID- 2190334 TI - Management of colon injuries. AB - The evaluation and management of colon injuries have recently undergone significant changes. The time-honored philosophy of conservative management by repair and diversion is giving way to a more aggressive approach, which includes primary repair of many injuries. The role of colostomy has been challenged by the need for additional operative procedures, patient disability, and rising hospital and medical costs. Based on the current literature, the authors have come to the following conclusions: 1. Primary repair is safe in carefully selected cases. 2. Colostomy should not be abandoned because of a fear of the morbidity associated with its closure. 3. The difference between injuries on the right and the left is questionable and probably not as significant as previously thought. 4. Exteriorized repair frequently requires conversion to colostomy and probably has little indication for use. 5. Short-term perioperative single-antibiotic coverage is sufficient. 6. Use of drains cannot be supported in most instances. 7. Wounds are best left open in patients with significant contamination. Surgical judgment remains the final arbiter in the decision process. These controversies and the debate generated have sharpened the guidelines for that judgment. PMID- 2190335 TI - Pancreatic trauma. AB - Pancreatic injuries are relatively uncommon and usually accompany injuries to major vessels or other gastrointestinal organs. Because it is these associated injuries that are responsible for the early morbidity and mortality, control of hemorrhage and bacterial contamination takes initial priority over the pancreatic injury. The management of specific pancreatic injury depends on the status of the main pancreatic duct, the degree of parenchymal damage, and the anatomic location of the injury. Complete visualization of the gland and accurate determination of the duct status are key intraoperative maneuvers. Failure to recognize significant pancreatic duct and parenchymal injury is the major cause of postoperative morbidity. The vast majority of pancreatic injuries can be managed by simple drainage with or without debridement or suture. However, the occasional major transection or pancreatic duct injury warrants rigorous efforts at determining the status of the major ducts. PMID- 2190337 TI - Management of massive hemorrhage associated with abdominal trauma. AB - Control of massive hemorrhage from intra-abdominal organs and major vascular structures may tax the ingenuity of the trauma surgeon. It is emphasized, however, that total blood loss and the amount of transfused blood are far less critical than the duration and severity of shock. PMID- 2190336 TI - Management of splenic injuries. AB - The structure and function of the spleen are reviewed in the context of providing a rational basis for splenic salvage after trauma. Guidelines for operative and nonoperative management are provided, and the results of treatment from recent large series are summarized. PMID- 2190338 TI - Retroperitoneal vascular injury. AB - Retroperitoneal vascular injuries are among the greatest challenges that confront the surgeon. Problems in resuscitation, exposure, and repair are numerous. Techniques to improve such perioperative tactics result in improved survival. PMID- 2190339 TI - Pelvic ring injuries. AB - Many problems may complicate the treatment of pelvic fractures. Thorough evaluation of the whole patient, all local structures, and the skeletal injury itself is essential. Continued bleeding due to unstable pelvic ring injuries is most effectively controlled by prompt anterior external fixation. Posterior shearing injuries are poorly stabilized by external fixation, and require additional treatment. Especially when significant deformity exists, or when the posterior injury is primarily ligamentous, open reduction and internal fixation are likely to be beneficial. PMID- 2190340 TI - Management of penetrating back trauma. AB - The best management plan for patients with stab wounds of the posterior abdomen who have no obvious indication for operation is a selective one. Repeated physical examination is the mainstay of treatment, as indicated by many authors. Other special studies, such as DPL, angiography, intravenous pyelography, and contrast CT scanning, are indicated on a case-by-case basis, but as yet lack convincing justification for routine use. PMID- 2190341 TI - Nonoperative management of abdominal trauma. AB - In an effort to reduce the rate of nontherapeutic celiotomy yet avoid the possibility of missed injuries, surgeons are evaluating protocols for nonoperative management of abdominal trauma. Discussion of this controversial issue includes specific approaches to the diagnosis and management of splenic injury, gunshot wounds, and stab wounds. PMID- 2190342 TI - Pre-, intra-, and postoperative antibiotics. AB - Endogenous contamination from perforation or rupture of the gastrointestinal tract; exogenous contamination from missiles, knives, or invasive lines and tubes; and immunodepression related to the severity of injury are responsible for the increased infectious complications noted in patients who have undergone laparotomy for abdominal trauma. Perioperative use of clindamycin and an aminoglycoside, a second- or third-generation cephalosporin, or an enhanced spectrum penicillin is clearly beneficial in lowering the incidence of intra abdominal and wound infections. A 12- to 48-hour length of administration of antibiotics after operation is as effective as regimens of longer duration, although presently used dosages may be inadequate in severely injured patients. Adjunctive surgical maneuvers such as peritoneal irrigation with saline containing antibiotic(s) remain controversial. Perioperative use of antibiotic prophylaxis, coupled with early operation and appropriate surgical technique, results in a 4.4% rate of intra-abdominal abscesses and a 5.1% rate of wound infections after laparotomy for abdominal trauma in modern trauma centers. PMID- 2190343 TI - Postoperative nutritional support of patients with abdominal trauma. AB - The response to major trauma is characterized by a significant erosion of the body cell mass. Intensive nutritional support can decrease morbidity and mortality. Preservation and restoration of the body cell mass involves amino acid synthesis into protein, and this process requires nutrient energy. Newer methods of assessing energy expenditure have revised traditional concepts about energy requirements following trauma. The use of fat to meet some of the caloric requirements may obviate problems with ventilatory distress, glucose intolerance, and hepatic steatosis that occur with glucose-based nutritional regimens. Selection of the delivery method for intensive nutritional support should consider gastrointestinal integrity, physiologic tolerance, and cost. Enteral nutrition is superior to parenteral nutrition in maintaining gastrointestinal mucosal integrity, hormonal balance, and nutrient utilization. Furthermore, it is safer, more convenient, and more economical than parenteral nutrition. PMID- 2190344 TI - Postoperative complications of abdominal trauma. AB - Postoperative complications following laparotomy for patients with abdominal trauma may be difficult to detect, particularly in those patients with multiple injuries. Such complications may lead to multiple organ system failure and death. Consequently, techniques for prevention of these postoperative complications, from resuscitation through operation, are emphasized. These techniques include means for detecting all abdominal injuries, management of the complicated wound, and evaluation and treatment of abdominal abscesses. PMID- 2190345 TI - Hemangioblastoma of the lateral ventricle. AB - A case of hemangioblastoma of the right lateral ventricle is presented. Only five other cases of intraventricular hemangioblastoma have been reported. The literature on supratentorial intraventricular hemangioblastoma is reviewed. PMID- 2190346 TI - Cure of cervical cancer using 252Cf neutron brachytherapy. AB - 252Cf neutron brachytherapy was tested in a feasibility trial for efficacy for cervix cancer therapy vs. high stage radioresistant and subsequently for all stages of disease. Actuarial survival curves were analyzed for 218 patients treated between 1976 and 1983 and followed five to 14 years to the present time. A variety of doses, schedules and methods for brachytherapy was tested during this period, and a dose-response relationship for tumor eradication studied. All treatments were combined with whole-pelvis photon radiotherapy to approximately 45 to 60 Gy. This combination was found effective, particularly if an early implant schedule was used for the Cf implant, followed by whole-pelvis photon radiotherapy. For bulky/barrel shaped low-stage disease in medically fit patients, 252Cf implants were combined with surgery, i.e., extrafascial hysterectomy and was readily usable for treatment without complications and with high cure rates (92% five-year survival). All survivals and outcomes to 13 years match the best results of conventional photon radiotherapy. For all stages better results were observed for bulky, barrel, and advanced-stage tumors, especially for local tumor control, if optimal schedules, doses and implant numbers were used. Knowledge about neutron dose, dose per implant, number of implants and combination with photon beam therapy evolved during the trials. 252Cf represents a new quick acting effective radioisotope for human cancer therapy especially for treatment of radioresistant, bulky and high stage cancers. PMID- 2190347 TI - [Bovine spongiform encephalopathy (BSE), a review]. AB - Bovine spongiform encephalopathy (BSE) is evolving rapidly as one of the major veterinary problems of the last few decades, confining itself for the time being to the United Kingdom and the Republic of Ireland. This article reviews the various disorders belonging to the progressive spongiform encephalopathies in humans and animals. It describes clinical symptoms, diagnosis, and experimental transmission of the newest member of this group, BSE. It goes on to discuss the origin of the disease, the latest events concerning BSE in the United Kingdom, and the chances for the disease to occur in the Netherlands. Whether BSE has any implications for human health is not completely clear. Risks for consumers seem remote and, if at all present, are probably confined to consumption of lymphatic and nervous tissues of clinically affected animals. PMID- 2190348 TI - Multicentric quality assurance in cardiac surgery. QUADRA study of the German Society for Thoracic and Cardiovascular Surgery (QUADRA: quality data retrospective analysis). AB - A method for initiating quality assurance in cardiac surgery was developed multicentrically by a commission of the German Society for Thoracic and Cardiovascular Surgery (QUADRA Study). To appraise the quality of cardiosurgical action, variables were compiled from the preoperative, intraoperative, and postoperative treatment course. The data collection was carried out at the same time as treatment. On the basis of unicentric data profiles, multicentric hospital profiles, and problem profiles, a quality comparison could be carried out and the variability of cardiosurgical action which may occasion interventions could be identified. A reduction of perioperative blood consumption during the study period could be observed in four out of five hospitals as the first result. The data collection also revealed epidemiological features. On average, women were older than men at the time of the heart-valve and coronary operations. To ensure data validity and the organization of quality assurance, a documentation assistant and a specially trained physician are necessary at every cardiovascular surgery center. The multicentric external comparison is indispensable and must be carried out by means of a central data collection, for which intrumental and staff capacities are also to be provided. With modern methods of data processing, an additional and new approach to the improvement of quality in cardiac surgery can thus be made. PMID- 2190349 TI - Myocardial protection and ischemia tolerance of the globally ischemic heart. AB - The pathophysiological fundamentals of the tolerance of the heart to the ischemic condition are discussed, with special reference to three contributions in Issue 1/1990 of this journal. The relationship 'duration of/damage done by' ischemia is of sigmoidal form. The time needed to recover from the damage caused is dependent on the extent of the damage and not on the duration of ischemia. This time is thus a measure of the damage caused. The two main means of reducing this damage are cardioplegia and hypothermia. The fundamental differences in the various cardioplegic methods, and the factors on which their effectiveness depends, are explained. The background to the use of hypothermia and the limits in its application are presented. The dependence on hypothermia to extend the useful duration of ischemia demands, however, a careful consideration of the physiological thermodynamics involved, when estimating the probable extent of damage reached at any time. PMID- 2190350 TI - Symptoms, diagnosis, and therapy of primary sarcomas of the pulmonary artery. AB - Primary sarcoma of the pulmonary artery is a rare tumor which must be considered in differential diagnosis of pulmonary embolism. The data of the 93 cases published up to now is evaluated synoptically after a report on a primary sarcoma of the pulmonary artery. Modern diagnostic imaging methods (pulmonary DSA, perfusion scintigraphy, echocardiography, computer tomography, nuclear magnetic resonance tomography) may corroborate the suspicion of a sarcoma of the pulmonary artery. With a median survival time of 1.5 months, the prognosis of patients with primary sarcomas of the pulmonary artery must be regarded extremely poor. After tumor excision, the median survival time of the patients could be prolonged (statistically significant; p less than 0.01) to ten months. The significance of adjuvant chemotherapy and/or radiotherapy cannot be appraised at present. PMID- 2190351 TI - [The pathogenesis of primary IgA-nephropathy]. AB - The pathogenesis of IgA nephropathy has remained elusive in the twenty years that have passed since the first description of the disease. Based on the recent literature, we present a pathogenetic model in which a primary disorder of immune regulation plays a central role. This disorder of immune regulation results in an increased synthesis of plasma IgAI antibodies by the bone marrow, in response to everyday mucosal infections. Through an unknown mechanism, these circulating IgAI antibodies deposit in the mesangium, and cause an inflammatory response. PMID- 2190352 TI - [At the death of Prof. J. Slooff]. PMID- 2190353 TI - [Functional morphology of the kidney. A review of the histophysiology of the kidney glomerulus, the nephrons and the collecting tubule system]. AB - The kidney is a composite organ, the specific activities of which are attributable to the peculiar construction of the individual components of the glomerula, nephrons and collecting tubules. This comprehensive review will address the essential physiological mechanisms of urine formation, such as filtration, secretion, reabsorption and concentration, and correlate these functions to morphological structures where possible. The complex structure of the renal glomerulus as the basis for the formation of primary urine (blood-urine barrier) will be documented on the basis of electron micrographs. In addition to this, the ultrastructure of the epithelium in the various tubular segments and collecting tubules will be discussed from a histophysiological stand-point, including its significance in the excretion of waste substances and maintenance of a constant fluid environment in the body (Homeostasis). PMID- 2190354 TI - [The significance of pregnancy-induced ketonuria in sheep and goats]. AB - The last third of pregnancy in sheep and goats is characterized by a considerable reduction in the volume of the rumen. When the animal is carrying more than one fetus there is thus a latent ketosis caused by starvation. A discrete hypoglycemia is in close correlation to this. If other special factors like increasing age of the pregnant animal, chronic liver disease, unbalanced nutrition containing too little carbohydrates are also present, the latent starvation ketosis can give rise to an acute gestation ketosis. The clinical picture is described in detail and contrasted with the gestation hypocalcemia. Furthermore, the parameters relevant to laboratory diagnosis will be discussed. PMID- 2190355 TI - [Ovarian structure and function in the mare from the clinical viewpoint with special regard to ultrasonography]. AB - Ultrasonography is a good means of monitoring follicular development in the mare and allows objective observation and measurement of follicular growth as well as identification of corpora lutea and hematoma in the ovary. The significance of ultrasonography in this field lies in the specific anatomical structure of the mare's ovary and the different phenomena preceding and accompanying ovulation, which are described in this paper. The last part deals with the handling and use of ultrasonography. PMID- 2190356 TI - Process chemicals in the oil and gas industry: potential occupational hazards. AB - Numerous chemicals are used in various processes of the oil and gas industry: drilling, cementing, completion, stimulation, and production. The number and the complexity of composition of process chemicals has increased greatly over the last three decades. The occupational hazards of exposure to these agents has received little attention. We reviewed the various processes in the industry, the type of chemicals used in each process, and some of their characteristics. We placed emphasis on those for which significant toxicity has been established or is suspected, and those for which there is incomplete information on their chemistry and health hazards. This report is intended to form a basis for a more complete survey of the process chemicals, and to draw attention to the possibilities for toxic exposure resulting from use of these agents in the oil and gas industry. The ultimate objective is to promote the safe use of these agents in the industry. PMID- 2190357 TI - Short term toxicity of nitrous oxide on the immune, hemopoietic, and endocrine systems in CD-1 mice. AB - Occupational exposures to subanesthetic levels of N2O have been documented to result in suppressed proliferative cell activities. Male CD-1 mice were exposed to 0, 50, 500, and 5000 ppm of N2O for 6 hr/day, 5 days/week for 2 or 13 weeks. Tritiated-thymidine ([3H]-TdR) uptake was measured in CD-1 splenic lymphocytes cultured with and without mitogens and in a mixed lymphocyte culture (MLC). Antibody-mediated immunocompetency was determined for sheep red blood cell (SRBC) sensitized animals by plaque forming cell (PFC) assay and serum anti-SRBC antibody (Ab) titer. Deoxyuridine suppression tests (dUrdST) were performed on bone marrow cells. There was significantly decreased splenic lymphocyte uptake of [3H]-TdR by cells cultured with mitogenic substances and in MLC following 2-week exposures to 5000 ppm. After 13-week exposures the animals' splenic lymphocytes showed increased [3H]-TdR uptake following high N2O dosing in both the mitogen induced blastogenesis and MLC assays. Compared to control animals, the 5000 ppm exposure group had significantly depressed PFC activity and circulating anti-SRBC Ab levels following the 13-week N2O exposures, and all 13-week exposure groups demonstrated decreased liver weights and leukopenia. Bone marrow activity at these dosing levels was depressed in a dose-dependent fashion following 13-week gas exposures. PMID- 2190358 TI - Mutagenicity, metabolism, and DNA interactions of urethane. AB - Urethane, a known animal carcinogen, has been the subject of intensive research efforts spanning 40 years. Recent concerns have focused on the presence of urethane in a variety of fermented foods and alcoholic beverages, although no epidemiological studies or human case reports have been published. Much information is available about the mutagenesis, metabolism, and DNA interactions of urethane in experimental systems. Urethane is generally not mutagenic in bacteria although in some instances it acts as a weak mutagen. Urethane is not mutagenic in Nuerospora but is weakly mutagenic in Saccharomyces. Drosophila appear to be the only organisms that consistently give positive mutagenic results with urethane, but its mutagenicity is weak and in many cases shows no clear dose dependence. Urethane is a good clastogen in mammalian somatic cells in vivo, but it shows variable results with cells in vitro. It efficiently induces sister chromatid exchanges in a variety of cells. Mammalian spermatogenic cells are insensitive to the induction of specific locus and dominant lethal mutations by urethane. Mutational synergism has been reported to occur between ethyl methanesulfonate and urethane when administered two generations apart, and some investigators have suggested possible synergism for cancer-causing mutations in mice exposed to X-rays and urethane one generation apart. These studies are controversial and have not been confirmed. Studies on the induction of cancer causing dominant mutations by urethane are at variance with results from extensive studies with the specific locus test in mice. Urethane studies with the unscheduled DNA synthesis assay in mouse spermatogenic cells and with the sperm abnormality test have given negative results. Urethane is rapidly and evenly distributed in the body. The rate of elimination of urethane from plasma is a saturable process and varies according to the strain and age of the animal. Recent studies have concentrations similar to those in wine, ethanol inhibits the tissue distribution of urethane in mice. These results are important because they suggest a lower carcinogenic/mutagenic risk than expected from exposure to urethane in alcoholic beverages. Although research on the metabolic activation of urethane has been extensive, no conclusive results have been obtained about its active metabolite, at one time thought to be N-hydroxyurethane. More recently, it has been postulated that urethane is activated to vinyl carbamate and that this metabolite is capable of reacting with DNA.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2190359 TI - Isolation and characterization of a hemorrhagin from the venom of Ophiophagus hannah (king cobra). AB - The major hemorrhagin (termed hannahtoxin) of the venom of Ophiophagus hannah (king cobra) was purified to electrophoretic homogeneity by DEAE-Sephacel ion exchange chromatography, Sephadex G-200 gel filtration followed by a second DEAE Sephacel chromatography. Proteolytic activity was associated with the hemorrhagic activity throughout the purification procedures. Hannahtoxin constituted approximately 2% of the crude venom. It had an isoelectric point of 5.3, a carbohydrate content of 12%, a mol. wt of 66,000 as determined by SDS polyacrylamide gel electrophoresis and 63,000 as determined by gel filtration. It contains 1 mole of Zn per mole of protein. The minimum hemorrhage doses for hannahtoxin are 0.7 microgram and 75 micrograms, respectively, in rabbits and in mice. Hannahtoxin was not lethal to mice at a dose of 2 mg/kg (i.v.) but killed rabbits at doses above 0.18 mg/kg (i.v.). It liberated protein from rabbit glomerular basement membrane but not rat glomerular basement membrane. Treatment of the hemorrhagin with EDTA and 1,10-phenanthroline eliminated both the proteolytic and hemorrhagic activities completely. PMID- 2190360 TI - Effects of toxin T-544 from the Karwinskia humboldtiana (buckthorn) plant upon mouse embryos explanted at 11 days. AB - Eleven-day mouse embryos were exposed to the K. humboldtiana toxin T-544 for 24 hr. At the end of the culture period, embryos were examined grossly for malformations and biochemically for altered protein levels. There was a significant difference in malformations in those embryos exposed to 0.05 and 0.2 microgram/ml of toxin compared with controls. Embryo protein content was significantly lower in those embryos exposed to 0.1 microgram/ml of T-544 compared with control group. PMID- 2190361 TI - Isolation and nucleotide sequence determination of a gene encoding a heat-stable enterotoxin of Escherichia coli. AB - An enterotoxin-producing strain of E. coli has been isolated from an infant patient in Shanghai Children Hospital and the gene of its heat-stable enterotoxin has been cloned and sequenced. The pre-pro-STI was composed of 72 amino acid residues corresponding to the encoding of 216 base pairs. There was only one nucleotide difference in the pro-part between this STI gene and the STIb gene reported in the literature. A guanosine base in our STI gene was substituted for a cytosine base in STIb gene resulting in a replacement of proline by alanine. Hence, the STI genes from different human sources are highly conserved though mutagenesis still occurs. PMID- 2190362 TI - Multiple intracerebral hemorrhages after smoking "crack" cocaine. AB - After smoking "crack" cocaine and consuming large quantities of ethanol, a 36 year-old man developed multiple, bilateral, deep, and superficial cerebral hematomas. He was hypertensive for several days, but angiography revealed no evidence of vascular malformation or vasculitis. The multifocality of the hematomas and lack of underlying disease suggest that the hemorrhages resulted from cocaine-induced acute hypertension or arterial spasm, possibly potentiated by heavy ethanol consumption. PMID- 2190363 TI - Influence of ranitidine on kinetics of nitrendipine and on noninvasive hemodynamic parameters. PMID- 2190364 TI - [Hemisphere differences in aging: an artifact]. AB - The observation that language processes in particular resist aging relatively well, gave rise to the hypothesis that the right hemisphere declines more rapidly than the left. In this review we discuss results from different lines of research relevant to this issue. It appears that the hypothesis is based on methodologically weak studies. Factors such as task characteristics, familiarity with stimulus materials and practice effects have been controlled insufficiently in the past and they may well explain the observed effects. Moreover, no clear neuropathological differences between the hemispheres have been reported. Therefore, it seems reasonable not to assume differential rates of aging for the two hemispheres. PMID- 2190365 TI - [Positive Romberg test and the probability of falls in the aged]. AB - Very little objective data are available on the subject of falling in the elderly. Yet there is an urgent need for simple tests to help identify those patients at risk. The predictive value of the Romberg-test was investigated with a group of 199 inhabitants of four homes for the elderly (76 had fallen three times in a period of six months and 123 never fell in a period of one year). Beside the age factor a positive Romberg-test meant an increased chance of falling. Elderly patients who fell but showed up as negative on the Romberg-test showed a marked tendency to stumble compared with the control group. The Romberg test is useful in identifying certain specific causes in falling but it is unsuitable for use within a preventative strategy. PMID- 2190366 TI - Humoral immune response following extracorporeal immunoadsorption therapy of patients with hypercholesterolemia. AB - Low-density lipoprotein apheresis (LDL-apheresis) is an extracorporeal procedure that preferentially removes LDL cholesterol from the blood. One of the primary techniques for performing this procedure uses immunoadsorption columns containing monospecific polyclonal sheep antibodies to human LDL covalently coupled to a gel filtration medium. LDL-apheresis has generally been well-tolerated, with chills, fever, or flushing occurring rarely. The possibility of an immune reaction was investigated as a basis for these reactions observed in 12 of the 1312 procedures performed. Antibodies to sheep IgG developed in 12 of the 15 patients treated with LDL-apheresis as a result of the shedding of small quantities of the sheep immunoglobulin from the columns. A column acid-washing procedure minimized the quantity of shed antibody but did not prevent immunization of the patient. The clinical reactions were probably unrelated to shedding and immunization, as the reactions occurred even in patients who were not immunized to the sheep IgG. Immunization to ethylene oxide was not the cause, as determined by a radioallergosorbent test. The reactions were more likely related to the activation of complement, as indicated by the generation of C3a des Arg by the columns and an increase in C3a des Arg levels systemically. PMID- 2190368 TI - The first recorded blood transfusions: 1656 to 1668. AB - The transfusion of blood was only one of many scientific competitions in which the citizens of France and England engaged in the 1600s. This particular competition laid the foundations for transfusion therapy that were built on 100 years later when more was known about blood. At the time of the studies discussed here, the most important goal seemed to be the establishment of the primacy of the discovery by one or the other nation. In this, most scholars give Lower and the English the first animal-to-animal transfusion and Denys and the French the first animal-to-man transfusion. However, even though this national primacy might not seem so important now, we must realize that the international competition created knowledge that still benefits us today, and those results might not have been produced so swiftly if the competition had not taken place. PMID- 2190367 TI - Fetomaternal hemorrhage: incidence, risk factors, time of occurrence, and clinical effects. AB - Most women have only very small amounts of fetal blood in their circulations following pregnancy and delivery: the volume is less than 0.5 mL of whole blood in 93 percent of women, less than 1 mL in 96 percent, and less than 2 mL in 98 percent. FMH of 30 mL or more occurs in just 3 of 1000 women. When the FMH was 150 mL or more, 15 of 41 infants did not survive Rh-negative women with FMH of more than 30 mL of Rh-positive whole blood are at increased risk of Rh immunization, and thus the outcome of their future pregnancies also may be affected. ABO-compatible fetal red cells that have entered the maternal circulation have a life span similar to that of adult cells. ABO-incompatible fetal red cells may be cleared rapidly, but in some cases they circulate for weeks. Most FMHs of 30 mL or more occur before labor, delivery, or cesarean section. The majority occur with minimal clinical signs and symptoms in apparently normal pregnancies. The identification of postpartum Rh-negative women who have 30 mL or more of Rh-positive fetal blood in their circulation is important so that sufficient RhIG for immune suppression can be administered. It appears that more than one-half of women with FMH of 30 mL or more would not be identified if protocols were adopted to test only women in pregnancies considered to be at high risk. PMID- 2190369 TI - The human body: belonging and control. PMID- 2190370 TI - The anencephalic neonate and brain death: an international review of medical, ethical, and legal issues. PMID- 2190371 TI - Immunofluorescence microscopy in experimental renal allo- and xenografts. PMID- 2190372 TI - Hyperacute rejection of renal discordant xenograft (pig-to-rabbit): model assessment and rejection mechanisms. PMID- 2190373 TI - Removal of IgM anti-endothelial antibodies results in prolonged cardiac xenograft survival. PMID- 2190374 TI - Prolongation of xenograft survival by exchange transfusions and immunosuppression. PMID- 2190375 TI - Pharmacokinetics of cyclosporine: inter- and intra-individual variations and metabolic pathways. PMID- 2190376 TI - An evaluation of cyclosporine monitoring by nonselective fluorescence polarization immunoassay. PMID- 2190377 TI - Nonselective measurement of cyclosporine for therapeutic drug monitoring by fluorescence polarization immunoassay with a rabbit polyclonal antibody: I. Evaluation of the serum methodology and comparison with a sheep polyclonal antibody in an 3H-tracer mediated radioimmunoassay. AB - Among the new techniques available for CyA monitoring, the FPIA offers the advantages of rapidity and simplicity. The present communication assesses the technical performance of this test in comparison with a 3H tracer-based PC-RIA for serum CyA levels using 971 samples obtained during the first 6 posttransplant months from 14 kidney transplant recipients. The FPIA evaluation included verification of CyA concentrations in manufacturer-supplied calibrators and controls by reference methods, determination of intraassay/interassay precision and accuracy, feasibility of specimen dilution and assessed assay sensitivity, and range of linearity. Comparison of FPIA with PC-RIA indicated that trough samples, when assessed by FPIA, averaged 1.3-fold greater than the PC-RIA, whereas non-trough FPIA measurements indicated similarity between the two methods. Although the two assays showed similar trends in most renal transplant recipients, two subjects demonstrated discrepancies, presumably reflecting the differing specificities of the polyclonal antibodies used in each assay. Thus, the FPIA appears to be a useful addition to CyA monitoring technology. PMID- 2190378 TI - Nonselective measurement of cyclosporine for therapeutic drug monitoring by fluorescence polarization immunoassay with a sheep polyclonal antibody: II. Evaluation of the whole blood methodology and comparison with an 3H tracer mediated radioimmunoassay with a sheep polyclonal antibody. PMID- 2190379 TI - A monoclonal antibody fluorescent polarization immunoassay for cyclosporine. PMID- 2190380 TI - A rapid and specific assay for the du Pont aca discrete clinical analyzer, performed directly on whole blood. PMID- 2190381 TI - Cyclosporine and the liver: how one affects the other. PMID- 2190382 TI - Pharmacokinetic interactions between cyclosporine and other drugs. PMID- 2190383 TI - French multicentre study: comparison of two specific and four nonspecific methods for Sandimmune (cyclosporine) blood and plasma (separated at 37 degrees C or at 22 degrees C) monitoring. PMID- 2190384 TI - Japanese conference on cyclosporine blood level monitoring. PMID- 2190385 TI - Quality assessment of cyclosporine measurements: comparison of current methods. PMID- 2190386 TI - Cyclophilin binding: a receptor-mediated approach to monitoring cyclosporine immunosuppressive activity following organ transplantation. PMID- 2190387 TI - Clinical correlations of cyclosporine HPLC and FPIA levels in renal transplant recipients. PMID- 2190388 TI - A prospective study of cyclosporine monitoring in renal transplantation. PMID- 2190389 TI - Comparison of the utility of 3H-based specific monoclonal antibody assay on whole blood samples with the fluorescence polarization nonspecific immunoassay on serum samples for diagnosis of adverse events in renal transplant patients. PMID- 2190390 TI - Renal side-effects of cyclosporine. PMID- 2190391 TI - Clinical evaluation and therapeutic range of cyclosporine A as monitored by FPIA in kidney transplantation. PMID- 2190392 TI - Is cyclosporine blood concentration monitoring necessary in patients treated for severe chronic plaque form psoriasis? PMID- 2190393 TI - Cyclosporine measurement by FPIA, PC-RIA, and HPLC following liver transplantation. AB - The factors affecting CyA dosing and kinetics in LT patients are complex, and have been thoroughly investigated and reviewed. Plasma or WB CyA concentration monitoring remains the best method presently available for adjusting CyA dosage in LT patients in a timely manner. The availability of an FPIA assay for CyA has produced rapid drug analysis for transplant patient monitoring, but adds additional factors that must be considered in interpreting CyA concentrations. Liver dysfunction may disproportionately elevate CyA plasma or blood levels when analyzed by FPIA in relation to PC-RIA or HPLC, and adjustment of the therapeutic range or analysis by a more specific assay method may be necessary for dosage adjustment in these patients. The availability of a more specific antibody in an FPIA assay may avert these problems, as would the development of immunologic monitoring techniques that provide a global assessment of immune suppression produced by increasingly complex immunosuppressive regimens in LT patients. PMID- 2190394 TI - Pharmacokinetic and pharmacodynamic studies of cyclosporine in bone marrow transplantation. PMID- 2190395 TI - Clinical correlations with cyclosporine blood levels after allogeneic bone marrow transplantation: an analysis of four different assays. PMID- 2190396 TI - Cyclosporine treatment of chronic graft-versus-host disease following allogeneic bone marrow transplantation. PMID- 2190397 TI - Steady-state concentrations of cyclosporine for therapeutic monitoring. PMID- 2190398 TI - Summary on therapeutic drug monitoring for renal transplantation. PMID- 2190399 TI - Consensus document: Hawk's Cay meeting on therapeutic drug monitoring of cyclosporine. PMID- 2190400 TI - Transplantation: the state of the art. PMID- 2190401 TI - [The results of and prospects for the study of the interphase nucleus of eukaryotes]. AB - Being devoted to studies in structural peculiarities of chromatin distribution of interphase nuclei from eucaryote cells, the paper embraces literature data and the authors' results in this field. Main tendencies in development of the method, based on the qualitative and quantitative estimation of hetero- and euchromatin nucleus substance are considered. Basic successes achieved while estimating experimental and clinical materials are indicated. It is determined as promising to put the method into practice. PMID- 2190402 TI - Caesarean birth. PMID- 2190403 TI - Reactive arthritis following Yersinia pseudotuberculosis infection. PMID- 2190404 TI - Use of intravesical bacillus Calmette-Guerin in the treatment of superficial transitional cell carcinoma of the bladder: an overview. AB - Since 1976 superficial bladder cancer is treated with intravesical instillations of Bacillus Calmette-Guerin (BCG). The results with BCG are superior to other intravesical chemotherapeutics, both in superficial tumors and carcinoma in situ. BCG probably acts as a nonspecific potentiator of the immune system. Comparative studies have to give information about the effectiveness and side effects of the different strains of BCG, and about the best clinical schedule. Toxicity is mild in 95% of the cases. Severe side effects and antituberculous drugs are discussed. PMID- 2190405 TI - Intravesical Bacillus Calmette-Guerin prophylactic treatment for superficial bladder tumors: results of a controlled prospective study. AB - A controlled prospective study in 100 patients evaluated the efficacy of intravesical bacillus Calmette-Guerin (BCG) administration as prophylactic treatment on tumor recurrence and tumor progression rate after endoscopic resection of superficial transitional cell carcinoma of the bladder. There were 27 recurrences in 22 of 67 evaluable patients (33%) who received BCG, compared to 27 recurrences in 19 of 33 control patients (58%) (p less than 0.05). The mean follow-up periods for the tumor-free patients in the BCG and control groups were 29 and 30 months, respectively, while the mean times to tumor recurrences for the above groups were 13.36 +/- 6 and 9.94 +/- 5 months, respectively (p less than 0.05). The recurrence rates per 100 patient months for the BCG and control patients were 1.69 and 4.41 recurrences, respectively (p less than 0.05), while 7 patients of the BCG group showed recurrent tumors of higher stage or grade, compared to 13 of the controls (p less than 0.05). This study confirms that Pasteur strain BCG is safe and efficacious in the prevention of superficial bladder tumor recurrence and tumor progression. PMID- 2190406 TI - Necrosis of the allograft ureter--evaluation of different examination methods in early diagnosis. AB - After renal transplantation, 16 of 1,109 patients (= 1.5%) developed an operatively confirmed necrosis of the allograft ureter. A review of these cases reveals that noninvasive ultrasonography, which was applied regularly with all patients, gave early indications of urologic complication. In cases of peritransplant fluid collection, renal transplant scintigraphy may be helpful in diagnosing a urinoma. In cases of renal graft failure with sonographic findings of perinephric fluid collection or hydronephrosis, antegrade pyelography--though more invasive--should always be performed given its low complication rate and improved visualization and pathological localization compared to other techniques. However, ureteral extravasation can be demonstrated only in cases of advanced necrosis; with necrosis just beginning and the wall still intact, frequently only the image of an obstruction is found. PMID- 2190407 TI - Cause of deviation of the erectile penis after urethral manipulations (Kelami syndrome)--demonstration of ultrasound findings and case reports. AB - The cause of deviation of the erectile penis after urethral manipulations is shown to be periurethral scarring which can be outlined by ultrasound investigation of the urethra and periurethral structures. Sonographic findings are demonstrated. 6 case reports are presented. PMID- 2190408 TI - Diarrhoea in adult horses: a survey of clinical cases and an assessment of some prognostic indices. AB - Samples of faeces and blood were obtained from 66 adult horses with diarrhoea. The results of routine bacteriological, parasitological, haematological and biochemical tests were correlated with the outcome of the cases. Twenty-two (33 per cent) of the horses died or were destroyed as a consequence of the diarrhoea. A diagnosis was reached in only 23 cases (35 per cent), and in nine of them only at post mortem examination. Salmonella typhimurium was isolated from five cases. Statistical analysis revealed significant differences between the horses which survived and those which died in their packed cell volumes, white blood cell counts, neutrophil counts, serum albumin concentrations and alkaline phosphatase activities. PMID- 2190409 TI - Competitive exclusion and Salmonella enteritidis. PMID- 2190410 TI - Captopril provides sustained hemodynamic benefits in dogs with experimentally induced mitral regurgitation. AB - Mitral regurgitation was created surgically in 10 dogs. After measurement of baseline hemodynamic parameters on day 2, treatment with captopril (2 mg/kg orally 3 times daily) was begun in five dogs. Five control dogs received no therapy during the study. The hemodynamic parameters were measured again at weeks 6 and 22. In the treated dogs, the forward ejection fraction (FEF) increased slightly and the total peripheral resistance index (TPRI) decreased. In the controls, the FEF decreased and the TPRI increased. Changes in FEF and TPRI were significantly different between the two groups. The change in FEF correlated significantly with the change in TPRI in both groups. Although the most dramatic changes were observed at week 6, the differences persisted throughout the study. Captopril administration resulted in sustained hemodynamic improvement and may, therefore, delay the onset of congestive heart failure in dogs with mitral regurgitation. PMID- 2190411 TI - Humoral immunity in the ewe. 1. The influence of adjuvancy and immunogenic substitution on immune reactivity following immunisation with protein antigens. AB - The nature of antigen and presence of adjuvant are major factors which influence the level of immune reactivity following immunisation. This study examines the quantity and isotype of antibody produced in ewes immunised with different proteins in combination with different adjuvants. Results using indirect ELISA assays show that animals immunised with keyhole limpet haemocyanin (KLH) in adjuvant produced lower levels (P less than 0.05) of immunoglobulin M (IgM) and had increased levels and persistence of immunoglobulin G1 (IgG1) compared with ewes immunised with antigen in saline (P less than 0.005). The anti-KLH immunoglobulin G2 (IgG2) titre was significantly higher in animals given oil emulsion adjuvant than all other groups (P less than 0.005). Ewes were also immunised with bovine serum albumin (BSA) or BSA haptenated with trinitrophenyl (TNP) for the primary injection and carrier BSA alone for the secondary inoculation. Chemical haptenation of BSA antigen reduced primary IgM (P less than 0.005), IgG1 (P less than 0.005) and IgG2 (P less than 0.005) levels compared with animals immunised with pure BSA. There was an increased secondary anti-BSA IgM response in all animals first immunised with TNP-BSA (P less than 0.05). The class of anti-hapten antibody produced to TNP determinants was influenced by the degree of TNP haptenation of the carrier BSA. Mid-range molar ratios of TNP produced the strongest IgM, IgG1 and IgG2 anti-TNP responses compared with all other groups (P less than 0.01). PMID- 2190414 TI - Perspective on hypertension in the elderly. AB - More than half of elderly men and women have hypertension, leading to a significant risk of increased morbidity and mortality. The cause of hypertension in this age group is unknown. Left ventricular hypertrophy is frequently present, often associated with diastolic dysfunction. Systolic hypertension in the elderly increases the risk of cardiovascular disease, but there are no good data to show that the treatment of isolated systolic hypertension reduces the morbidity or mortality. Good evidence indicates that antihypertensive treatment in this group decreases cardiovascular morbidity and mortality up to age 80, so most elderly hypertensive patients should be treated. An empiric trial of nonpharmacologic therapy can be initiated in those with mild hypertension and no cardiovascular disease, but most patients will require drug therapy. Most elderly hypertensive patients have accompanying illnesses for which they may or may not be taking medications. Some antihypertensive drugs exacerbate coexisting diseases while others augment treatment regimens. Similarly, drugs may interact in a beneficial or adverse way. Finally, drug metabolism is altered by age, leading to problems with toxicity or diminished efficacy. The choice of medication should be based on all such considerations, including the cost and convenience of the drugs available. PMID- 2190415 TI - Prenatal diagnosis of Noonan's syndrome in a female infant with spontaneous resolution of cystic hygroma and hydrops. PMID- 2190413 TI - Current management of the Wolff-Parkinson-White syndrome. AB - The Wolff-Parkinson-White syndrome is a multifaceted disorder that ranges from asymptomatic to life threatening. Accounting for approximately 20% of cases of paroxysmal supraventricular tachycardia and with a prevalence perhaps as high as 1 per 500, it is far from a rare disorder. Considering the potentially lethal complications following the administration of digoxin or verapamil, all physicians treating arrhythmias should know when to suspect the Wolff-Parkinson White syndrome. A careful review of electrocardiograms helps identify cases of the disorder despite a wide range of findings that may mimic other conditions. Major advances in the efficacy of surgical procedures to cure this syndrome make this a reasonable alternative to life-long medical therapy for many patients. Unfortunately, available diagnostic tests lack the positive predictive value to reliably distinguish patients at risk of sudden death. This review is an update for general internists of the major developments in the evaluation and treatment of the disorder and provides specific examples helpful in differentiating these patients. PMID- 2190412 TI - Physical diagnosis versus modern technology. A review. AB - The role of physical diagnosis in an age of modern diagnostic technology has been evaluated by investigators assessing specific techniques in a number of areas, though there has been no systematic comprehensive study of the sensitivity, specificity, cost-benefit ratio, and reliability of physical diagnosis relative to technologic diagnostic tools. In a review of published studies comparing physical with nonphysical diagnostic techniques, the startling accuracy of physical diagnosticians in some areas contrasts sharply with the extremely poor correlation of physical findings with autopsy or imaging studies in others. In a time of constricting financial resources, physicians-and those who teach or judge physicians' skills-must begin to compare physical and nonphysical diagnostic techniques rigorously so that the best, safest, and least expensive diagnostic test is chosen in each clinical situation. PMID- 2190416 TI - Dupuytren's disease. AB - Dupuytren's disease is an extremely common malady, affecting as many as 3% of the general population. Presenting features are variable and include simple asymptomatic palmar nodules or refractory contractures of the interphalangeal joints. Substantial associations with knuckle pads, plantar nodules, and Peyronie's disease are noteworthy. Although a strong familial tendency is present, the precise pathologic mechanism is unknown. Treatment is frequently unnecessary, but when indicated it includes a variety of surgical alternatives. An appropriately timed referral to a surgical specialist before irreversible contracture of the interphalangeal joints can prevent a permanent loss of function. When surgical intervention is not elected, careful and regular follow up is necessary to detect early joint contracture. PMID- 2190417 TI - The new disease model of alcoholism. AB - The new biopsychosocial disease model of alcoholism is examined from the perspective of recent biologic research. Studies of animal and human genetic predispositions suggest the presence of genetic influences over drinking behavior as well as biologic risk factors related to deficiencies in various neurochemicals. Ethanol affects the fluidity of cell membrane lipids, eventually causing membrane dysfunction. It also adversely affects the activity of two enzymes, monoamine oxidase and adenylate cyclase, that have important functions in the information processing system of the brain. Research on condensation products formed in the brain after alcohol consumption has provided clues to the development of alcoholism, but many questions remain unanswered. Alcoholism is clearly a multidimensional phenomenon in which biologic, psychological, and sociocultural factors interact to produce illness. PMID- 2190418 TI - Chemical dependency and drug testing in the workplace. AB - Urine testing for drug use in the workplace is now widespread, with the prevalence of positive drug tests in the work force being 0% to 15%. The prevalence of marijuana use is highest, and this can be reliably tested. Though it is prudent to rid the workplace of drug use, there is little scientific study on the relationship of drug use and workplace outcomes, such as productivity and safety. Probable-cause testing and preemployment testing are the most common applications. Random testing has been less accepted owing to its higher costs, unresolved legal issues, and predictably poor test reliability. Legal issues have focused on the right to policy, discrimination, and the lack of due process. The legal cornerstone of a good program is a policy that is planned and agreed on by both labor and management, which serves both as a contract and as a procedure in which expectations and consequences are known. The National Institute on Drug Abuse is certifying laboratories doing employee drug testing. Testing methods when done correctly are less prone to error than in the past, but screening tests can be defeated by adulterants. Although the incidence of false-positive results is low, such tests are less reliable when the prevalence of drug abuse is also low. PMID- 2190419 TI - The role of physicians as medical review officers in workplace drug testing programs. In pursuit of the last nanogram. AB - In discussing the role of physicians in workplace drug testing programs, I focus on the recent Department of Transportation regulations that require drug testing in such regulated industries as interstate trucking, air transportation, mass transit, and the railroads. These regulations require that applicable drug testing programs employ physicians as medical review officers to evaluate positive tests that have been screened and confirmed by different techniques to determine if there is a legal medical explanation for the result. The drug testing program tests for the presence of amphetamine, cocaine, tetrahydrocannabinol, opiates, and phencyclidine. If an employee testing positive has an acceptable medical explanation, the result is to be reported as negative. Little practical advice exists for medical review officers, and they must be aware of key elements of the regulations and potential trouble spots. PMID- 2190420 TI - Pulmonary complications of smoked substance abuse. AB - After tobacco, marijuana is the most widely smoked substance in our society. Studies conducted within the past 15 years in animals, isolated tissues, and humans indicate that marijuana smoke can injure the lungs. Habitual smoking of marijuana has been shown to be associated with chronic respiratory tract symptoms, an increased frequency of acute bronchitic episodes, extensive tracheobronchial epithelial disease, and abnormalities in the structure and function of alveolar macrophages, key cells in the lungs' immune defense system. In addition, the available evidence strongly suggests that regularly smoking marijuana may predispose to the development of cancer of the respiratory tract. "Crack" smoking has become increasingly prevalent in our society, especially among habitual smokers of marijuana. New evidence is emerging implicating smoked cocaine as a cause of acute respiratory tract symptoms, lung dysfunction, and, in some cases, serious, life-threatening acute lung injury. A strong physician message to users of marijuana, cocaine, or both concerning the harmful effects of these smoked substances on the lungs and other organs may persuade some of them, especially those with drug-related respiratory complications, to quit smoking. PMID- 2190422 TI - Primary care for AIDS and chemical dependence. AB - Primary care clinicians are acquiring an increasingly important role in preventing, diagnosing, and treating both chemical dependence and human immunodeficiency virus (HIV) illness. Towards this end they need to know the epidemiology of HIV infection in chemically dependent persons and methods of educating persons at high risk for these problems. It is critical that physicians screen for alcohol and drug addiction. Health care providers should understand the risks and benefits of HIV antibody testing and include in their practices the basic components of counseling before and after testing and informed consent. Both HIV illness and addiction are chronic diseases with long-term health implications. A knowledge of patient characteristics, intensity of treatments, and treatment modalities is important in making recommendations for individualized therapy. Combining service delivery is a future challenge necessitated by today's joint epidemics of the acquired immunodeficiency syndrome and chemical dependence. PMID- 2190421 TI - Cognitive impairments in abstinent alcoholics. AB - Impaired cognitive functioning in alcoholics is widespread during the first months of detoxification. Between half and two thirds of abstinent alcoholics exhibit cognitive impairments during this period, with residual deficits persisting for years after detoxification in some patients. The most severe deficits have been observed in visuospatial abilities, perceptual-motor integration, abstract reasoning, and new learning. The most significant predictors of cognitive dysfunction in persons recovering from alcoholism are the time elapsed since the last drink and the person's age. Surprisingly, the pattern and duration of a patient's alcohol abuse are relatively weak determinants of neuropsychological impairment during abstinence. Research investigating the hypothesis that cognitive impairments may be related to alcoholic persons resuming drinking has yielded mixed results, but a higher level of neuropsychological functioning is associated with increased rates of completing treatment programs and with greater success in the work environment after discharge from treatment. The possibility of cognitive limitations should be taken into account in planning treatment programs for alcoholism. PMID- 2190423 TI - Drug abuse, psychiatric disorders, and AIDS. Dual and triple diagnosis. AB - Substance abuse and psychiatric disorders commonly occur together. This form of dual diagnosis is notable because it complicates assessment and makes treatment more difficult for both psychiatric and drug abuse problems. Drugs can cause psychiatric disorders and can also be used as an attempt to "cure" them by self medication. The spread of the human immunodeficiency virus (HIV) among drug users has added a third potential clinical problem, that of the acquired immunodeficiency syndrome, to the difficulties already presented by drug abuse and psychiatric disorders. Patients with this triple diagnosis pose challenges to primary care physicians as well as addiction medicine specialists or psychiatrists. Assessment should include a drug abuse history, preferably corroborated by others, evaluation of the mental state, and examination focusing on signs of drug abuse and HIV infection. Treatment should include the management of HIV disease, abstinence from drug abuse, and access to psychiatric care. New systems of health care service, including interdisciplinary case management, may be needed to manage patients with a triple diagnosis. PMID- 2190424 TI - Drug-exposed neonates. AB - Drug use during pregnancy can have detrimental effects--both nonspecific and highly specific--on the perinatal outcome. Nonspecific effects include fetal growth retardation, resulting in small infants and decreased head circumference. Specific effects include facial dysmorphology and organ system anomalies such as alcohol-related birth defects. Patients abusing drugs are at an increased risk for preterm labor, thereby placing an already compromised fetus at increased risk. The number of mothers and infants being infected by the human immunodeficiency virus from sharing needles, multiple sexual contacts, and mother to-infant transmission is increasing at an alarming rate. PMID- 2190426 TI - Expert systems in treating substance abuse. AB - Computer programs can assist humans in solving complex problems that cannot be solved by traditional computational techniques using mathematic formulas. These programs, or "expert systems," are commonly used in finance, engineering, and computer design. Although not routinely used in medicine at present, medical expert systems have been developed to assist physicians in solving many kinds of medical problems that traditionally require consultation from a physician specialist. No expert systems are available specifically for drug abuse treatment, but at least one is under development. Where access to a physician specialist in substance abuse is not available for consultation, this expert system will extend specialized substance abuse treatment expertise to nonspecialists. Medical expert systems are a developing technologic tool that can assist physicians in practicing better medicine. PMID- 2190425 TI - Cigarette smoking, nicotine dependence, and treatment. AB - Since the 1988 Surgeon General's report on nicotine addiction, more attention is being given to nicotine dependence as a substantial contributing factor in cigarette smokers' inability to quit. Many new medications are being investigated for treating nicotine withdrawal and for assisting in long-term smoking abstinence. Medications alone probably will not be helpful; they should be used as adjuncts in comprehensive smoking abstinence programs that address not only the physical dependence on nicotine but also the psychological dependence on cigarette smoking. PMID- 2190428 TI - Ultrastructural investigation of the meningeal compartment of the blood cerebrospinal fluid-barrier in rats and cats. A horseradish peroxidase study. AB - The permeability of the meningeal blood vessels and cellular layers to horseradish peroxidase was studied 5, 10 and 15 minutes following intravasal or intraarachnoidal introduction of the marker. When applied intravasally, the horseradish peroxidase-containing solution easily passed through the walls of all meningeal vessels (dural, pial and the ones traversing the arachnoid space). The cells of the inner dural layer and dural neurotheliun delay the penetration of horseradish peroxidase into the cerebrospinal fluid-filled arachnoid space by 10 min--rats and 15 min--cats. The perivascular leptomeningeal cells and their processes restrict the passage of the marker into the arachnoid space in a similar way. These barrier functions of the leptomeningeal cells and the cells that comprise the interface zone between dura mater and the arachnoid are confirmed by experiments where the marker was injected into the arachnoid space. PMID- 2190427 TI - Methadone maintenance in the treatment of opioid dependence. A current perspective. AB - We describe the historical underpinnings of negative attitudes towards methadone and how these affect medical decisions. Current developments have increased the understanding of the origins of opioid addiction, such as how receptor system dysfunction may affect the ability to remain abstinent once out of treatment. Specialized topics include the pregnant addict, the role of methadone maintenance in limiting the spread of the acquired immunodeficiency syndrome, and patients with a dual diagnosis. We also describe issues that arise when methadone is used in conjunction with prescribed or abused drugs, noting pharmacologic alternatives and adjuncts to methadone treatment. Finally, we comment on treatment issues such as methadone patients in 12-step programs and the growing legitimacy of this treatment method. PMID- 2190429 TI - In praise of John Lynch, "inspiring and dedicated leader". PMID- 2190430 TI - The alcohol dehydrogenase system in the yeast, Kluyveromyces lactis. AB - We have studied the alcohol dehydrogenase (ADH) system in the yeast Kluyveromyces lactis. Southern hybridization to the Saccharomyces cerevisiae ADH2 gene indicates four probable structural ADH genes in K. lactis. Two of these genes have been isolated from a genomic bank by hybridization to ADH2. The nucleotide sequence of one of these genes shows 80% and 50% sequence identity to the ADH genes of S. cerevisiae and Schizosaccharomyces pombe respectively. One K. lactis ADH gene is preferentially expressed in glucose-grown cells and, in analogy to S. cerevisiae, was named K1ADH1. The other gene, homologous to K1ADH1 in sequence, shows an amino-terminal extension which displays all of the characteristics of a mitochondrial targeting presequence. We named this gene K1ADH3. The two genes have been localized on different chromosomes by Southern hybridization to an orthogonal-field-alternation gel electrophoresis-resolved K. lactis genome. ADH activities resolved by gel electrophoresis revealed several ADH isozymes which are differently expressed in K. lactis cells depending on the carbon source. PMID- 2190431 TI - Cell fusion of Saccharomyces cerevisiae fragile mutants. AB - Fragile mutants of Saccharomyces cerevisiae are defective in the structure of the cell wall and plasma membrane. The mutant cells lyse in hypotonic solutions but grow exponentially when osmotic stabilizer is included in the medium. These mutants display a general increase in the permeability of the plasma membrane. We show here that fragile yeast cells of the same mating type can fuse without protoplast formation. The frequency of cell x cell fusion is lower than that observed for protoplast x protoplast fusion and can be significantly increased if the cells of one partner are converted to protoplasts. Microscopic observations and genetic analysis demonstrate that the hybrids obtained are fusion products. The fusion between fragile cells is explained in terms of the existence of local defects on their surface where the cell wall is thinner (or even missing), thus allowing a direct contact of cells by means of their plasma membranes. PMID- 2190432 TI - Bacterial plasmid pBR322 sequences serve as upstream activating sequences in Saccharomyces cerevisiae. AB - The expression of acid phosphatase (APase) from PHO5 and MF alpha-PHO5 hybrid genes is regulated by inorganic phosphate and mating type locus respectively, as well as the PHO4 and MAT alpha 1 gene products respectively. When PHO5 and MF alpha-PHO5 hybrid genes were cloned in the BamHI site of the pBR322 sequence of the yeast shuttle vectors (YRp7 or YEp9T), in one orientation they were regulated normally but in the other orientation their expression was not regulated but expressed constitutively. The pBR322 sequences present upstream of the inserted genes are responsible for the constitutive expression. By replacing the PHO5 upstream activating sequences (UAS) element with pBR322 fragments, we have identified three pBR322 sequences, from nucleotides 376 to 650, 2068 to 2116 and 2136 to 2247, which were able to promote expression of APase. A comparison of these three pBR322 fragments revealed 5' ATCGCGCGAG 3' and 5' CGGTGATGNCGG 3' to be the common sequences likely to act as UASs in Saccharomyces cerevisiae. By using synthetic oligonucleotides, it was found that both sequences are required for maximum expression of APase activity. PMID- 2190433 TI - The start gene CDC28 and the genetic stability of yeast. AB - The cdc28-srm mutation in Saccharomyces cerevisiae decreases spontaneous and induced mitochondrial rho- mutability and the mitotic stability of native chromosomes and recombinant circular minichromosomes. The effects of cdc28-srm on the genetic stability of cells support the hypothesis that links cell cycle regulation in yeast to changes in chromatin organization dependent on the start gene CDC28 (Hayles and Nurse, 1986). PMID- 2190434 TI - GABA transport in Saccharomyces cerevisiae. AB - Gamma-aminobutyrate (GABA) accumulation in growing cultures of Saccharomyces cerevisiae was shown to occur by means of an active transport system that is inhibited by proton ionophores, azide, fluoride and arsenate ions. Transport occurred maximally at pH 5.0 and exhibited apparent Km values of 12 microM and 0.1 mM. Accumulated GABA did not efflux upon treatment with proton ionophores and exchanged with extracellular material only very slowly. However, release was complete upon treatment with nystatin. These observations raise the possibility that a major portion of intracellular GABA is sequestered in the vacuole. The response of GABA uptake to growth on various nitrogen sources suggested that uptake may be subject to several types of regulation. PMID- 2190435 TI - [The value of magnetic resonance tomography (MRT) in inflammatory rheumatic diseases]. AB - As compared to other imaging modalities, magnetic resonance imaging (MRI) is characterized by superior soft tissue contrast, multiplanar display, and lack of ionizing radiation and other hazards. Contrast media, including paramagnetic substances, (e.g., gadolinium-DTPA) are useful for further improvement of diagnostic capabilities of MRI. In this paper the results of MRI in rheumatoid arthritis and related disorders, as well as the potentials of its clinical use are discussed. PMID- 2190436 TI - [The treatment of ankylosing spondylitis with auranofin (Ridaura)]. AB - Auranofin has no influence on axial skeleton manifestation of ankylosing spondylitis, neither on clinical complaints, nor on function and inflammatory parameters. Peripheral arthritis is possibly influenced positively, but this cannot be stated definitely because of the low number of cases in this study. This question must be analyzed in larger collectives, as alternatives to conventional therapy are needed for the treatment of peripheral joint involvement of ankylosing spondylitis. PMID- 2190437 TI - Imaging in pancreatic pain. PMID- 2190438 TI - Enzyme therapy and pancreatic pain. PMID- 2190439 TI - Abdominal aortic aneurysms. Is there an association between surgical volume, surgical experience, hospital type and operative mortality? Members of the Norwegian Abdominal Aortic Aneurysm Trial. AB - The effects of number of operations, experience of the surgeon, and type of hospital on operative mortality have been studied in 444 patients treated for abdominal aortic aneurysms. In the elective group (n = 279) there was a significant difference in mortality between hospitals in which more than 10 such operations were done compared with those in which less than 10 were done during the study period (p = 0.05; odds ratio (OR) 2.7). In the ruptured group there was no statistically significant difference (p = 0.14; OR 1.9). In the elective group, units with vascular surgical experience had an operative mortality of 4.8% compared with 11.3% for other units (p = 0.05; OR 2.6). In the ruptured group the figures were 52.5% and 73.3% respectively (p = 0.03; OR 2.5). There was no difference in operative mortality between university, county and local hospitals. Outcome of treatment after operations for abdominal aortic aneurysm was related to number of operations carried out and experience, whereas the type of hospital seemed less important. PMID- 2190440 TI - Intraoperative ultrasound as an aid to surgical strategy in liver tumor. AB - Ultrasonography of the liver was performed on 27 patients during laparotomy for liver lesions--11 primary and 13 metastatic mainly colon/rectum malignancies, and three benign conditions. Supplementary information on the liver parenchyma was provided in 11 cases (41%) in which the surgical strategy was decided simply by inspection and palpation of the liver. Ultrasound was most valuable for visualizing the vascular anatomy of the liver, giving clarification in 18 cases (66%), especially the relationship of tumor to portal and hepatic veins. This was decisive for the surgical strategy in four cases, enabling resection in two and modifying planned procedure in two. In a case of polycystic liver, ultrasonography imaged deep-lying cysts and aided the fenestration procedure. Liver resection was performed in 16 cases without operative mortality. Hepatic ultrasonography is useful for determining tumor spread, but of even greater value for the determination of strategy by clarifying tumor/vascular anatomic relationships. PMID- 2190441 TI - Choledochotomy for biliary lithiasis: is routine T-tube drainage necessary? A prospective controlled trial. AB - Thirty patients with stones in the common bile duct were allocated alternately to have choledocholithotomy carried out with either T-tube drainage or with primary closure. Choledochoscopy was done during every operation, and the patency of the common bile duct tested by perfusion. There were no operative deaths. The length of operation was shorter with primary closure (p less than 0.01) but there were no differences between the groups in operative blood loss, days in hospital after operation, postoperative morbidity and mortality, and final outcome at follow up. There was no change in the incidence of postoperative bacteraemia, the number of adverse reactions, and the incidence of bile peritonitis after removal of the T tube. Patients who had T-tubes reported greater discomfort and inconvenience than those without, and their treatment cost more. We conclude that primary closure of the common bile duct is a reasonable alternative to T-tube drainage in selected cases. PMID- 2190442 TI - Microalbuminuria in diabetic children and adolescents. Relationship with puberty and growth hormone. AB - Urinary albumin excretion (UAE) was determined by radioimmunoassay in two 24 h urine collections from 125 diabetic children and adolescents and from 71 normal children matched for age and sex. Thirteen patients (10.4%) aged greater than 12 years had microalbuminuria, i.e. log transformed UAE levels above the upper normal range (24.5 mg/24 h). UAE values were positively correlated with age, GH secretion, but not with duration of disease, glycosylated hemoglobin, renal size or N-acetyl-beta-glucosaminidase excretion. Diabetic normoalbuminuric children aged 10 years and older had significantly higher UAE than controls and than younger diabetic patients matched for duration of disease. HLA DR3/DR4 heterozygosity frequency was significantly higher (p less than 0.01) in the microalbuminuric group than in the normoalbuminuric. All microalbuminuric subjects (n = 8) with short duration of disease (3.92 +/- 3.43 yr) developed diabetes at puberty. In conclusion, our cross-sectional study suggests: if a number of factors are combined, i.e. HLA DR3/DR4 heterozygosity, onset of disease at puberty and higher GH values, the probability of developing abnormal levels of UAE will increase. PMID- 2190443 TI - [Lymphangioma of the mediastinum as a cause of chylopericardium]. AB - Chylopericardium is a rare from of pericardial effusion. A case of a ten-year-old female patient with a chylopericardium incidentally detected during a mild respiratory infection through cardiac enlargement at the chest X ray is reported. The techniques used to achieve this diagnosis are described, a special emphasis being put on the CT-scan and lymphangiography, which have not been used in such cases so far. These techniques provided very useful data which were determinant for the success of the proposed therapy. This and other cases reported in the paper indicate that the most common cause of primary chylopericardium is a mediastinal lymphangioma. PMID- 2190444 TI - [Neurochemical and structural changes in schizophrenia--correlation with the clinical picture]. AB - This article reviews progress in elucidating the nature of the disease process in schizophrenia. It discusses the evidence for biochemical and structural changes and concludes that both are present and perhaps can be related to different components of the clinical picture. PMID- 2190445 TI - [Maillard compounds as a cause of aging]. AB - Several theories have been presented to explain the mechanism of aging. Among those theories, two are supported by strong reasons: the generation of oxygen radicals and nonenzymatic glycosylation of proteins. Oxygen and glucose are essential for the central nervous system (and practically for all tissues) and at the same time they are the main cause of aging. Through our demonstration that Maillard compounds generate oxygen free radicals, both theories may be united in one. PMID- 2190446 TI - The regulatory hierarchy controlling sex determination and dosage compensation in Caenorhabditis elegans. PMID- 2190447 TI - Combinatorial associations of regulatory proteins and the control of cell type in yeast. PMID- 2190448 TI - Internal movements in immunoglobulin molecules. PMID- 2190449 TI - Molecular basis of human leukocyte antigen class II disease associations. PMID- 2190450 TI - Immune privilege and immune regulation in the eye. PMID- 2190451 TI - T lymphocyte-derived colony-stimulating factors. PMID- 2190452 TI - Adverse effects of anticoagulants. PMID- 2190453 TI - Aspects of pesticide toxicology. AB - Pesticides are currently perceived by the public as posing a major long-term threat to the health of the population. While the acute toxic effects of accidental or intentional ingestion of large doses are accepted, very little is known about the health risks associated with chronic occupational exposure or a life-long intake in food and drinking water. As in most cases of risk assessment, it is the relative risks that must be considered. Pesticides have made a vital contribution to the quality and quantity of food and overall to health both in developed and, most significantly, developing countries, so that their sudden withdrawal would present far more serious health problems than do their potential long-term toxic effects. Genetic engineering may develop seeds that are naturally resistant to many plant diseases, and biological methods of insect control are likely to be used more frequently, but the continued use of pesticides will be necessary for many more years. There is a pressing need for research into the chronic health effects in man of low-level exposure to pesticides, the mechanisms of the toxic effects, and the development of reliable methods for monitoring exposure. The responsibility for ensuring that this work is undertaken must be accepted by governments. PMID- 2190454 TI - Dr. Lumpkin: a pilgrim's progress. PMID- 2190455 TI - Dermatologic manifestations of HIV infection. AB - Nearly all patients infected with the human immunodeficiency virus (HIV) will develop cutaneous or mucous membrane manifestations. Oral cavity lesions associated with HIV disease include candidiasis, hairy leukoplakia and Kaposi's sarcoma. Skin infections such as herpes simplex, herpes zoster, molluscum contagiosum, Staphylococcus aureus folliculitis and warts are often more severe than usual and may be refractory to therapy. Seborrheic dermatitis is the most common cutaneous eruption. The appearance of Kaposi's sarcoma in a patient younger than 60 years of age or in any individual with laboratory evidence of HIV infection is diagnostic of acquired immunodeficiency syndrome. Serious drug reactions may occur, despite the depressed cellular immunity associated with HIV infection. PMID- 2190456 TI - Black hairy tongue. AB - Black hairy tongue is a benign disorder characterized by hypertrophy of the filiform papillae of the tongue. A brownish-black discoloration of the papillae occurs. The etiology is unclear, but the disorder has been associated with numerous predisposing conditions. Although black hairy tongue is usually cured by removal of these factors, a variety of measures, particularly brushing of the tongue, may aid in resolution. PMID- 2190457 TI - Screening for lung cancer. From the U.S. Preventive Services Task Force. PMID- 2190458 TI - Retroperitoneal fibrosis. AB - Retroperitoneal fibrosis, an uncommon and ill-defined condition, has a variety of causes and presenting features. The fibrotic process often produces ureteral obstruction and compression of surrounding structures. Pain in the flank, lower abdomen or lumbosacral region is the most common presenting symptom. Certain drugs, neoplasms, retroperitoneal injury or infections may all initiate the fibrotic process. This article describes a case of retroperitoneal fibrosis in a 34-year-old man who had been receiving a beta-adrenergic blocking agent. PMID- 2190459 TI - Study of HIV vaccine begins. PMID- 2190460 TI - Efficacy of isosorbide-5-mononitrate on painful and silent myocardial ischemia after myocardial infarction. AB - The anti-ischemic efficacy of isosorbide-5-mononitrate, 20 mg 3 times daily, on silent myocardial ischemia after myocardial infarction was studied in 28 Chinese patients with use of 48 hours of ambulatory electrocardiographic monitoring in a randomized, crossover, single-blind, placebo-controlled study. Isosorbide mononitrate reduced both painful and painless episodes of ischemia compared with placebo. The number of total ischemic episodes was reduced 88%, duration of ischemia 94%, time-ischemia integral 95%, and total maximal ST-segment depression 86% (p less than 0.01). The drug did not alter the heart rate and blood pressure, and had no evident adverse effect. Thus, isosorbide mononitrate is effective and well tolerated in postinfarction patients with silent ischemia. PMID- 2190461 TI - A dose-finding study of the hemodynamic effect of isosorbide dinitrate spray in congestive heart failure. AB - A dose-finding study of the hemodynamic effect of a new formulation of isosorbide dinitrate (ISDN) spray was performed in 12 patients with chronic congestive heart failure. Doses of 1.25, 2.5, 5.0 mg and placebo, as 1 squirt, were randomly given to all patients. Hemodynamic measurements were performed by a Swan-Ganz catheter before and at 30 seconds and 1, 5, 10, 20 and 30 minutes after drug administration and every 30 minutes thereafter, until return of hemodynamic variables to baseline. Hemodynamic improvement evident as decreases in right sided pressures and an increase in cardiac output was observed within 1 minute from administration of ISDN spray, and peaked at 5 minutes. Near maximal effect was achieved by the 2.5-mg dose. Thus, 2.5 mg of ISDN spray (new formulation) dose. Thus, 2.5 mg of ISDN spray (new formulation) produces rapid, near-maximal hemodynamic improvement in patients with congestive heart failure. PMID- 2190462 TI - Randomized double-blind comparison of isosorbide dinitrate and nifedipine in variant angina pectoris. AB - The antianginal and anti-ischemic effect of isosorbide dinitrate (ISDN), 120 mg once daily, and nifedipine, 20 mg twice daily, both in slow-release formulations, were compared in 17 patients with variant angina pectoris in a randomized, double blind trial. The design included a placebo run-in period and two 6-week crossover periods of active treatment. Mean frequency of angina decreased significantly from 43 attacks per week during the placebo period to 4 per week with ISDN and 8 with nifedipine (p less than 0.001). Sublingual nitroglycerin consumption decreased significantly from 37 tablets per week with placebo to 3 tablets per week with ISDN and 7 with nifedipine (p less than 0.001). Both drugs reduced the silent and symptomatic ST-segment deviations on ambulatory electrocardiographic recording and increased maximal exercise tolerance. Episodes of coronary spasm could be provoked, by hyperventilation, in all patients during the placebo phase but in no patient during therapy with either active drug. Thus, both ISDN and nifedipine, in their slow-release formulations, are effective in the treatment of variant angina pectoris. PMID- 2190463 TI - Intravenous isosorbide-5-mononitrate in the treatment of acute myocardial infarction. AB - The action of isorsorbide-5-mononitrate (IS-5-MN) infusion (range 6.0 to 10.0 mg/hour) was studied in 24 patients with and without acute heart failure (hemodynamic subsets I to IV) during acute myocardial infarction. Hemodynamic measurements were performed by right-sided cardiac catheterization. Intravenous IS-5-MN demonstrated significant hemodynamic effects compared with baseline values. In subsets I and II, a decrease in pulmonary wedge pressure (PWP) and in cardiac index (CI), without significant changes in heart rate, mean arterial pressure or systemic vascular resistance index were demonstrated. In subsets III and IV, a major increase in CI and a decrease in systemic vascular resistance index, as well as a decrease in PWP were found. Again no changes occurred in mean arterial pressure and heart rate. The dosage was similar in subsets I to IV (8.0, 7.9, 7.8 and 7.3 mg/hour); thus, the differences in the responses could not be attributed to dosage. It appears that several different patterns of hemodynamic IS-5-MN action exist, assuming that IS-5-MN operates on preload and afterload levels. The action of IS-5-MN mechanisms seems to be dependent on an initial hemodynamic subset. No patient had any deleterious hemodynamic effects. A decrease in CI in subsets I and II was not of clinical importance with these dosages. No nitrate tolerance during 9.0 hours of continuous therapy appeared.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190464 TI - Evaluation of the efficacy and duration of action of isosorbide mononitrate in angina pectoris. AB - The magnitude and duration of the antianginal and anti-ischemic effects of isosorbide mononitrate (IS-5-MN), 20 mg, were determined in 10 patients with chronic stable angina pectoris. An exercise test (treadmill, Bruce protocol) was performed before and at 1, 6, 8 and 10 hours after oral administration of the drug. The patients were randomly assigned to receive IS-5-MN or placebo, and after 1 week of therapy were crossed over to the other formulations. The drug increased the exercise duration from 321 to 455 seconds at 1 hour (p less than 0.001). Time to moderate angina increased from 237 to 324 seconds (p less than 0.05) and time to ST depression greater than or equal to 1 mm increased from 150 to 307 seconds (p less than 0.01) at 1 hour. Placebo had no effect on any of the exercise parameters. Although partially attenuated at 6 hours, the effect of IS-5 MN remained statistically significant even at 8 hours, but not at 10 hours. It is concluded that the duration of action of a single tablet of IS-5-MN, given orally, is 8 hours. PMID- 2190465 TI - Changing dietary patterns. AB - Previously traditional dietary patterns in Japan are no longer typical. The current changing conditions provide an opportunity to examine more closely some important health conditions associated with the changed lifestyle and concentrations of dietary total fat and saturated fatty acid, and the ratio of n 3 to n-6 polyunsaturated fatty acids in the diet. PMID- 2190466 TI - Sodium excretion and hyperfiltration during glucose infusion in man. AB - The relations between renal hemodynamics (Inutest, CPAH) and sodium excretion were studied in 7 nondiabetics in whom a similar expansion was induced (1) with a 3-hour 5% glucose infusion and (2) with a 0.9% saline load. With both infusions the body weight increased, hematocrit fell, and the plasma renin activity was suppressed. During glucose infusion, blood glucose rose from 3.9 mmol/l to a plateau of around 13 mmol/l; glycosuria was absent during the 1st h, then appeared and stabilized during the following 2h. Glucose infusion caused a progressive increase in glomerular filtration rate and in renal blood flow in both absence and presence of glycosuria, without significant changes in sodium excretion despite volume expansion and increase of filtered sodium load. When saline was infused, there was a sustained increase of fractional sodium excretion, and no hemodynamic modifications were observed. We suggest that a primary glucose-induced metabolic stimulation of sodium reabsorption may play a role in the genesis of glucose-induced hyperfiltration. PMID- 2190467 TI - Diabetic hypouricemia as an indicator of clinical nephropathy. AB - We studied the possible association of the low serum uric acid level with incipient diabetic nephropathy in non-insulin-dependent diabetes mellitus (NIDDM). Of 201 NIDDM patients without a diminished glomerular filtration rate, 66 patients (32.8%) showed moderate hypouricemia of less than the mean-1 SD of 201 nondiabetic controls. Thirteen (6.5%) showed marked hypouricemia of less than the mean-2 SD. Hypouricemic patients showed normal daily urinary urate excretion with a markedly elevated urate clearance/creatinine clearance ratio. Most were under poor glycemic control, and presented either negative or intermittent clinical proteinuria. However, neither poor glycemic control, nor the presence of proteinuria or retinopathy alone significantly affected the serum uric acid level of the whole diabetic population. The glomerular filtration rate was determined in comparable groups of diabetic patients with hypouricemia and nonhypouricemic diabetic controls. The hypouricemic group showed a significantly higher endogenous creatinine clearance and lower serum beta-2-microglobulin levels than the nonhypouricemic group. These findings suggest that the hypouricemic group had a higher glomerular filtration rate. Long-term observation of up to 12 years of the above patients revealed that, in most patients, persistent hypouricemia was observed prior to the initial appearance of intermittent proteinuria. We hypothesize that glomerular hyperfiltration also occurs in NIDDM and that it lowers the serum uric acid by increasing the renal clearance of urate. Hypouricemia may also predict the future progression of incipient nephropathy in NIDDM. PMID- 2190468 TI - Impressive reduction of serum beta 2-microglobulin in a patient treated with a new polyamide hemofilter. PMID- 2190469 TI - Urine electrolytes and osmolality: when and how to use them. AB - The purpose of this review is to provide an update on the use of the urine electrolyte and osmolality measurements in patients with disorders of fluid, electrolytes, and/or acid-base metabolism. It is critical to appreciate that there are no 'normal values' for these parameters, only 'expected values' relative to clinical situations. Pitfalls in the interpretation of each electrolyte in the urine are also provided. To detect a mild to moderate degree of reduction of the 'effective' intravascular volume, both urine sodium (Na) and chloride (Cl) concentrations should be measured. Pitfalls in this assessment are abnormal renal and adrenal function and the use of diuretics. Insights into the etiology of the low 'effective' intravascular volume can be deduced by comparing the urine Na, potassium (K), and Cl concentrations. The urine net charge (Cl vs. Na + K) is the most reliable way to estimate the urine ammonium concentration short of its direct measurement, an assay that is not provided by most laboratories. This measurement is important in the differential diagnosis of hyperchloremic metabolic acidosis. To examine the renal response to hypokalemia or hyperkalemia, the two components of K excretion (K secretion and urine flow rate) should be examined separately. The former is evaluated using the transtubular K, concentration gradient. The urine osmolality is used to assess antidiuretic hormone action and the osmolality of the renal medulla and to determine the etiology of polyuria and/or hypernatremia. The urine osmolality can also be used to assess the ammonium concentration, using the urine osmolal gap, and to detect unusual urine osmoles. PMID- 2190470 TI - In vivo expression of perforin by natural killer cells during a viral infection. Studies on uveitis produced by herpes simplex virus type I. AB - A potent cytolytic pore-forming protein (PFP, perforin, or cytolysin) is associated with the cytoplasmic granules of cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. The role of PFP/perforin in cytolytic reactions carried out in vivo is still unclear. Here, the authors performed immunohistochemical analysis using antibodies monospecific for perforin and made use of a murine uveitis model produced by intracameral inoculation of herpes simplex virus I (HSV-I). The main cell infiltrate found in the anterior segment of virus-inoculated eyes consisted of Thy-1+/asialo GM1+/CD8-/CD4- cells, presumably representing NK cells. Perforin staining was detected mainly in cells bearing this phenotype. Perforin was only detected in cells displaying the large granular lymphocyte morphology. A small number of perforin-positive cells (less than 5%) colabeled as CD8+, indicating that these cells could have belonged to the CTL lineage. These observations show for the first time the presence of perforin-containing NK cells in tissues of animals undergoing acute viral infections. PMID- 2190471 TI - Heterogeneity of smooth muscle cells in atheromatous plaque of human aorta. AB - This study was undertaken to investigate the expression of cytoskeletal proteins and the ultrastructure of cells in normal intima and atheromatous plaque of human aorta. It has been established, using double-labeling immunofluorescence, that smooth muscle cells (SMC) in normal aortic intima contain myosin, vimentin, and alpha-actin but do not react with antibodies against desmin. In contrast, 7 of 28 atherosclerotic plaques contained many cells expressing desmin in addition to the other cytoskeletal proteins characteristic of normal intima SMC. These cells were localized predominantly in the plaque cap and had the ultrastructural features of modulated SMC, ie, well-developed endoplasmic reticulum and Golgi apparatus. Besides, some cells in the 13 atherosclerotic plaques proved to be myosin, alpha actin, and desmin negative but contained vimentin and actin as revealed by fluorescent phalloidin. These cells were found in the immediate proximity of atheromatous material and reacted with a monoclonal antibody specific to SMC surface protein (11G10) but not with monoclonal anti-muscle actin (HHF35) and anti-macrophage (HAM56) antibodies. Electron microscopy of this plaque zone revealed that the cytoplasm of these cells was filled with rough endoplasmic reticulum and a developed Golgi complex. At the same time, a certain proportion of cells in this region retained morphologic features of differentiated SMC such as the presence of a basal lamina and myofilament bundles. The revealed peculiarities of cytoskeletal protein expression and the ultrastructure of cells in human aortic atherosclerotic plaques may be explained by a phenotypic modulation of vascular SMC. PMID- 2190472 TI - Skeletal biological distance studies in American physical anthropology: recent trends. AB - Biological distance analysis, the dominant type of skeletal biological research during the 19th century, has become less visible in recent years. Although the proportion of American Journal of Physical Anthropology articles and published abstracts focusing on biodistance has remained fairly constant over the three decades between 1955 and 1985, the proportion of biodistance contributions relative to other skeletal biology studies has decreased. Emphasis in skeletal biology has shifted from the analysis of biological variation to investigations of health and diet, and within biodistance studies methodological issues have assumed prominence over purely analytical approaches. This paper investigates trends in biological distance analysis through a survey of articles and meetings abstracts published in the American Journal of Physical Anthropology from 1955 to 1985. The survey provides the historical context for five symposium papers on skeletal biological distance presented at the 1986 meeting of the American Association of Physical Anthropologists. PMID- 2190473 TI - Cranial metric and discrete trait variation and biological differentiation in the terminal Late Archaic of Ohio: the Duff site cemetery. AB - Cranial metric and discrete traits were collected from adult individuals of the terminal Late Archaic Duff site cemetery (33 LO 111). Comparisons of cranial metric traits among eight terminal Late Archaic samples including the Duff site sample showed that all samples shared the same generalized variance and by inference the same pattern of shape variation. Some significant size differences were found but these were interpreted as reflecting only minor differences in the underlying polygenic system or differences in environmental interactions. The overall similarity in cranial metrics among the terminal Late Archaic samples strongly suggests that they represent populations that, at least, shared a recent common ancestor. Analysis of discrete trait variation in all the terminal Late Archaic samples showed that the biological distances between samples are associated significantly with the between-sample geographical distances. This association accounts for approximately 25% of the variation in discrete trait frequencies. These results along with the results of the analysis of cranial metrics indicate that all of the terminal Late Archaic samples considered here are related, but geographically nearer samples are more closely related than distant ones. PMID- 2190474 TI - Population structure and skeletal variation in the Late Woodland of west-central Illinois. AB - This paper analyzes nonmetric trait variation in 11 late Late Woodland (ca. AD 700-1000) and one Mississippian (AD 1000-1300) skeletal samples from west-central Illinois from a population-structure perspective. Most of the sites are of the Bluff phase of Late Woodland in the lower Illinois River valley; others are from a nearby, contemporary archaeological phase. Late Woodland as a whole era (ca. AD 250-1000) was a period of marked population growth and expansion into new regional environments, trends that accompanied horticultural intensification in the area. Overall variation between sites was low, but males, females, and the total sample exhibited a significant geographic component to variation due to interregional morphological differences. The Bluff sites tended to group together relative to the non-Bluff sites. However, there was no significant geographic component to variation among the Bluff sites. The results are only partially consistent with archaeological data suggesting population growth and expansion through fissioning. Previous studies have demonstrated significant heterogeneity for nonmetric trait frequencies among Middle Woodland (ca. 100 BC to AD 250) sites, suggesting a Middle to Late Woodland change in population structure that lowered levels of morphological variation. This supports a model of increased intra- and interregional interaction from Middle to Late Woodland times developed from ceramic data by Braun and by Braun and Plog. PMID- 2190475 TI - Craniometrical variation among South American prehistoric populations: climatic, altitudinal, chronological, and geographic contributions. AB - The independent contributions of climate, altitude, chronology, and geographic location of archeological sites to craniometrical variation are analyzed in a sample of 1,119 skulls from South America. Geographic location is responsible for the highest proportion of craniometrical variation, followed by climate and altitude. It is concluded that geographic isolation has partially prevented gene flow from counterbalancing craniometrical microdifferentiation produced by founder effect. PMID- 2190476 TI - Primary Roux-Y gastrojejunostomy versus gastroduodenostomy after antrectomy and selective vagotomy. AB - One hundred twenty-one patients with prepyloric ulcer disease entered a randomized clinical trial comparing gastroduodenostomy with Roux-Y gastrojejunostomy after antrectomy and selective gastric vagotomy. The postoperative course and morbidity were quite similar in the two study groups, as was the postoperative infectious complication rate. Forty-four of the patients with a Billroth I reconstruction and 52 of those with a Roux-Y reconstruction were followed up with a clinical assessment at least 6 months after the operation. The postgastrectomy symptoms were quite frequent, but did not differ between the two study groups. Seventy-five percent of the patients with a Billroth I gastroduodenostomy had symptoms corresponding to Visick grades 1 and 2, compared with 81% of those with Roux-Y reconstruction. Although the latter procedure was very effective in preventing bile reflux to the gastric remnant, no difference was observed in the gastric emptying rate after the two operations. PMID- 2190477 TI - Estimation of genetic correlation: interpretation of experiments using selectively bred and inbred animals. AB - There is increasing interest in determining the extent to which multiple characters related to drug sensitivity are influenced by common genes. The principal method for testing for the existence of such genetic correlations has been examination of pairs of mouse or rat lines selectively bred for sensitivity or resistance to a single behavioral effect of a drug. When a pair of selected lines is found to differ significantly on some trait other than the one on which they were selected, it is commonly concluded that significant genetic correlation between the traits exists, implying the action of a common set of genes on the two responses. In addition, results from comparisons of lines of animals selected for trait X and tested for trait Y may be compared with results from lines selected for trait Y and tested for trait X. As the number of correlated responses in selected lines increases, it becomes more important to adhere to sensible, consensual guidelines for interpreting such line differences. The principles underlying phenotypic and genotypic correlational analyses with selected lines are discussed. A scheme is presented to allow standardization across laboratories of inferences about the relative strength of genetic association from experiments with selected lines. Statistical and practical experimental issues are addressed. Estimates of genetic correlations may also be derived from the correlation of mean trait values across a panel of inbred strains. Existing data have sometimes found estimates of genetic correlations made with one approach to be inconsistent with those estimated in other ways. Possible reasons for this are discussed. Finally, the relationship between phenotypic correlations and genetic correlations is discussed. Phenotypic and genetic correlations for a pair of traits may differ widely, and may even be opposite in sign. Both are characteristic of the population from which they are sampled. Phenotypic correlations estimated within selected lines may change over time, as the additive genetic variance in the selected trait is exhausted. A specific example of this phenomenon is given. PMID- 2190478 TI - Alcohol consumption and menstrual distress in women at higher and lower risk for alcoholism. AB - This study investigated whether alcohol consumption varied as a function of menstrual cycle, menstrual distress symptomatology, and global stress in nonalcoholic drinking young women at higher and lower (HR, LR) risk for alcoholism as assessed by family history. Eighty-two normally menstruating women (52 LR and 30 HR) monitored their alcohol intake, physical and affective distress symptoms, and global stress level daily for two consecutive menstrual cycles. Subjects were unaware that their menstrual cycles were being monitored. The results confirmed the presence of increased physical distress symptomatology during the premenstrual and menstrual phases but did not show variation in negative affect or global stress throughout the menstrual cycle. High risk subjects were aware that they were at higher risk for alcoholism and consumed more alcohol. However, alcohol consumption was not related to the menstrual cycle, distress symptoms, or global stress. Subjects reported that they drank most frequently with others for pleasure enhancement and rarely for pain or tension-reduction. Subjects also drank more on weekends than weekdays. These findings argue against the menstrual cycle as etiological in the development of alcoholism. It would appear that social factors influence alcohol consumption in young nonalcoholic women. PMID- 2190479 TI - Protein synthesis in bone and skin of the rat are inhibited by ethanol: implications for whole body metabolism. AB - The acute effects of ethanol (75 mmol/kg body weight, intraperitoneal) on rates of protein synthesis in bone tibia) and skin of young (approximately 100 g body weight) laboratory rats was investigated. Plasma ethanol levels were raised to approximately 40 mmol/liter. At 2.5 hr, rates of protein synthesis were measured with a flooding dose of L-[4-3H]phenylalanine. In bone the protein-bound specific radioactivities, fractional synthesis rates, and synthesis rates relative to RNA and DNA were significantly reduced by approximately 30%. In skin these variables similarly decreased in response to ethanol treatment, by approximately 25%. The reduction in absolute rates of protein synthesis in bone (delta, 0.7 g protein/day/kg body weight) and skin (delta, 3.4 g protein/day/kg body weight) were comparable to the reductions in liver and skeletal muscle in response to acute ethanol. As bone and skin contribute to a quarter of whole body protein synthesis, it was concluded that these observations may have important implications for whole body protein homeostasis. PMID- 2190480 TI - Alcoholism treatment: a ten-year follow-up study. AB - Two hundred male and female patients, selected at random from all patients admitted to an inpatient alcoholism treatment facility in 1973-1974, were surveyed 10 years following treatment. Response rate was 80%, and a validity check was done. Of the 158 unstable responses, 61% reported complete or stable remission of their alcoholism for at least 3 years prior to the survey and 84% reported stable psychosocial status. Successful outcome was possible regardless of severity of drinking history or psychosocial status. Seventy-six percent (76%) of those still alive at follow-up reported remission; at most, 23% of the deceased were reported in remission prior to death. Involvement in Alcoholics Anonymous (AA) predicted abstinence, suggesting successful outcome for patients who undergo a treatment regimen, which bridges patients into AA involvement. Of those respondents who continued to sponsor other AA members throughout the follow up period, 91% were in remission at the time of survey. PMID- 2190481 TI - Interaction of ethanol with enflurane metabolism and toxicity: role of P450IIE1. AB - Administration of enflurane (EF), a widely-used anesthetic agent, sometimes results in occult liver injury. As hepatic cytochromes P450 oxidize EF to a reactive intermediate, we assessed whether one such microsomal enzyme, ethanol inducible P450IIE1, plays an obligatory role in EF metabolic activation and hepatotoxicity. Liver microsomes from rats fed ethanol (36% of total calories for 14 days) oxidized 1 mM EF (measured by its defluorination) at rates nearly 10 fold greater than those from control rats, reflecting the markedly enhanced content of immunoreactive microsomal P450IIE1 in the former animals. P450IIE1 involvement in hepatic EF oxidation was further suggested by the pronounced inhibition of microsomal defluorination noted with P450IIE1 antibodies and with ethanol, a specific substrate for this enzyme. EF administration to rats treated chronically with ethanol caused significant elevations in plasma levels of aspartate and alanine aminotransferases and glutamate dehydrogenase, indicative of hepatic injury, whereas concurrent treatment of naive rats with EF and ethanol failed to produce the same effect. Our results imply that ethanol-inducible P450IIE1 is the primary catalyst of hepatic EF bioactivation and that the increased bioactivation occurring in vivo secondary to chronic ethanol consumption is attendant with an increased incidence of EF hepatotoxicity. PMID- 2190482 TI - Body composition in detoxified alcoholics. AB - Body composition was evaluated in healthy detoxified alcoholics (aged 20-39) and lifestyle controls, with the expectation that prolonged, excessive consumption of alcohol may bring about nutritional or toxicologic alterations in the relationship between body fat and lean body mass. Body fat was assessed by measurements of skin-fold thickness and by means of bioelectric impedance methodology. No noteworthy differences were observed between alcoholics and controls with regard to the relationship between lean body mass and body fat or in the relationship between extracellular and intracellular water. It would appear that 15-20 years of heavy alcohol consumption does not necessarily alter body composition in healthy, young alcoholics. PMID- 2190483 TI - Ad libitum alcohol ingestion does not induce renal IgA deposition in mice. AB - This study investigated the induction of alcohol abuse related IgA glomerulonephritis in mice, a disease we have previously described in humans and in rats with noncirrhotic alcoholic liver disease. A commercial liquid diet was fed ad libitum to 115 mice from three strains: C57BL/6J, BALB/cJ, and C3H/HeJ. Animals were divided into two groups: 60 received 30% of their caloric intake as ethanol--alcoholized; and 55 were fed the same calorie count in the form of glucose-controls. Mice were killed at weekly intervals after 4 to 10 weeks of liquid diet ingestion. No diagnostic renal pathology was observed. PMID- 2190484 TI - In vivo neutrophil delivery in men with alcoholic cirrhosis is normal despite depressed in vitro chemotaxis. AB - Ten patients with far-advanced Laennec's cirrhosis were studied for in vitro polymorphonuclear (PMN) chemotaxis and in vivo PMN delivery into modified skin windows. Random motility was similar for patient and control cells, but the patients' cells' mean chemotaxis to endotoxin-activated homologous serum was only 38% of control. The poor response was due to a serum inhibitor which reduced chemotactic activity of control serum by 75.6% but had no effect on chemotaxis to N-formyl-methionyl-leucyl-phenylalanine. The level of inhibitor activity in each patient did not correlate with the severity of liver dysfunction. In spite of the universal presence of the chemotactic factor inhibitor in all patients' sera, their in vivo PMN delivery into skin chambers was similar to controls. Thus, patients with alcoholic cirrhosis appear able to deliver PMNs normally in response to local tissue injury. PMID- 2190485 TI - Further characterization of LSxSS recombinant inbred strains of mice: activating and hypothermic effects of ethanol. AB - Lines of mice selected for differential initial sensitivity to the anesthetic effects of ethanol also differ in their locomotor responses to lower doses of ethanol. Sixteen recombinant inbred strains of mice derived from long-sleep (LS) and short-sleep (SS) selected lines as well as inbred LS and SS mice were used in a genetic correlational study to investigate possible associations between high dose and low-dose indices of initial sensitivity to ethanol. Measurements of high dose (4.1 g/kg) effects of ethanol were hypothermia, sleep time, and blood ethanol content at regaining of righting response, and the index of low-dose (1.875 g/kg) sensitivity was distance traveled during a 5-min period immediately following intraperitoneal injection with ethanol. The results indicated wide genetic variation in hypothermia and ethanol-induced locomotor activation in a manner consistent with polygenic influence. Furthermore, correlations between low dose locomotor activity and hypnotic dose effects tended to be low and nonsignificant, indicating independence of inherited mechanisms underlying high- and low-dose ethanol sensitivity. PMID- 2190487 TI - Immunotoxicity of alcohol in young and old mice. I. In vitro suppressive effects of ethanol on the activities of T and B immune cells of aging mice. AB - A murine aging model was employed to assess effects of ethanol exposure on the T cell proliferative response to mitogenic stimulation and on the T cell-dependent primary antibody response to sheep red blood cells (RBC) in vitro. Splenic cells from young (3-5 months) and old (28-32 months) BALB/c mice were first assessed for their ability to produce interleukin (IL) 2 and proliferate in response to mitogenic stimulation in the presence of various doses of ethanol. Then, splenic T blast cells from young and old mice, generated by Con A-activation, were assessed for their IL2-dependent proliferative capacity in the presence of various doses of ethanol. Finally, splenic cells of young and old mice were assessed for their ability to generate plaque-forming cells (PFC) in response to sheep RBC in the presence of various doses of ethanol. The results revealed that ethanol has a much greater suppressive effect on old than young splenic T cells (10-15 times), as judged by their ability to proliferate in response to mitogenic stimulation. However, the magnitude of the difference in the suppressive effect is less when the cells are cycling (2 times). Furthermore, ethanol had only a minimal suppressive effect on IL2 production by T cells of both young and old mice, even at the concentration of 100 mM. These findings would suggest that the ethanol-mediated suppression of T cell proliferation of both young and old mice is more likely due to an impairment of metabolic event(s) associated with or subsequent to the interaction of IL2 and IL2 receptor leading to cellular replication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190486 TI - Alcohol intoxication blunts sympatho-adrenal activation following brain injury. AB - In 46 patients experiencing traumatic brain injury, we studied the interactions of alcohol intoxication and severity of neurologic dysfunction on the resulting sympathetic nervous system activation. Sixty percent of the variation in norepinephrine (p less than 0.0001) and more than 50% of the variation in epinephrine (p less than 0.0001) were due to the initial ethanol concentrations and extent of brain injury assessed by the admission Glasgow Coma Score (GCS). As brain function deteriorated plasma cathecholamines rose (p less than 0.0001), but ethanol qualitatively and quantitatively modified this observation. The magnitude of the sympathetic response to worsening neurologic function was progressively diminished in association with increasing ethanol levels, i.e., the inverse relationship of GCS values with both norepinephrine and epinephrine was flattened. In comatose patients (GCS less than 8) increasing ethanol levels was associated with progressively decreasing norepinephrine and epinephrine responses (p less than 0.04), such that catecholamines were reduced by 80 to 90% at ethanol concentrations approaching 400 mg/dl (87.0 mmol/l). However, the impact of ethanol on the degree of sympathetic nervous system activation depended upon the degree of injury; the apparent ethanol suppression was greatest in patients with the most severe neurologic dysfunction (GCS 3 or 4), but it diminished as neurologic function improved. We conclude that the presence of alcohol appears to modify the rise in catecholamine levels following traumatic brain injury in a dose-dependent manner and alters the relationship between neurologic dysfunction and SNS activation. These alterations may have profound effects on patient morbidity in the immediate post-accident period. PMID- 2190488 TI - Familial transmission of alcohol use norms and expectancies and reported alcohol use. AB - Members of 183 families (biological parents and one adult offspring) completed questionnaires on their quantity and frequency of alcohol use, what they would consider a "normal" quantity-frequency of alcohol use, "problem" quantity frequency of use, flushing after alcohol use, and other expected physiological and subjective responses to alcohol. Within individuals, own quantity-frequency of alcohol use was moderately negatively correlated with flushing after one drink or less ("fast flushing"), but more highly positively correlated with judged normal alcohol use and with expected subjective effects. Spouse resemblances were low for quantity-frequency of alcohol use and flushing, but high for alcohol use norms and expected physiological and subjective responses. Parent-offspring resemblances were low to moderate for own alcohol use and flushing, but moderate to high for expected physiological and subjective effects. These results were discussed in terms of the effects of genetically transmitted flushing after alcohol use and culturally transmitted alcohol norms and expectations on alcohol use. PMID- 2190489 TI - The influence of sociodemographic characteristics on familial alcohol problems: data from a community sample. AB - The moderating influence of race (black versus white), age, sex, and socioeconomic status on the relationship between alcohol abuse/dependence in offspring and a family history of alcoholism/problem drinking was investigated in a representative general population sample (N = 1659). Significant family history by race by age and family history by race by sex interactions were observed when predicting lifetime risk of alcohol abuse/dependence in offspring. Socioeconomic status did not moderate the effect of familial alcoholism/problem drinking on offspring alcohol abuse/dependence. Relative odds ratios indicated that the risk of alcohol abuse/dependence associated with a positive family history increased with increasing age among whites; whereas, it decreased with increasing age among blacks. Among whites, the relative odds ratio for the effect of family history was higher for females than for males; however, among blacks it was higher for males than females. Although these findings need to be replicated in other populations, they suggest that it is important to take race, age, and sex into consideration when investigating familial alcohol problems. PMID- 2190490 TI - The HK/MBD questionnaire: factor structure and discriminant validity with an adolescent sample. AB - A somewhat revised four-factor structure emerged for the HK/MBD questionnaire with a sample of nonclinical adolescents. The three factors of hyperactivity/impulsivity, antisocial/oppositional behaviors, and learning problems largely retained their factor integrity, but a distinct peer dysfunction factor replaced attentional/socialization problems with the adolescent sample. Acceptable levels of internal consistency were found for three of the factors (excluding learning problems), and interrater reliability between adolescents and their primary caregivers was significant for all four factors. High factor intercorrelations were reported for hyperactivity/impulsivity and antisocial/oppositional behaviors. Differential predictive relations were found between the four factors and adolescent problem behaviors. Specifically, hyperactivity/impulsivity and antisocial/oppositional behaviors were most highly correlated with externalizing symptoms such as alcohol problems, delinquency, illicit drug use, and poor school performance. Peer dysfunction was most highly correlated with internalizing, depressive symptoms. Learning problems correlated most highly with poor school performance, and moderately with alcohol problems and depressive symptoms. There were no statistically significant differences in the strength of the interrelations between the factors of the HK/MBD questionnaire and adolescent problem behaviors for males and females. PMID- 2190491 TI - Alterations in interleukin-2 utilization by T-cells from rats treated with an ethanol-containing diet. AB - Administration of ethanol to Sprague-Dawley rats has been shown to produce a defect in lymphocyte proliferation in response to concanavalin A. Because a critical element in T-cell proliferation is the production of interleukin-2, experiments were designed to evaluate the influence of ethanol on the production and utilization of interleukin-2 by spleen cells from ethanol-treated animals. To ensure that changes in spleen cell responses to mitogenic stimulation were not simply caused by a loss of responding T cells, we tested nylon wool-nonadherent cells. The response to concanavalin A of isolated T cells from ethanol-treated rats was consistently less than that of equivalent numbers of cells from control animals. The addition of recombinant interleukin-2 to cultures of T cells did not correct the defect in proliferation to concanavalin A noted in cells from ethanol treated rats. Further study results demonstrated that interleukin-2 production by T cells from ethanol-treated animals was equal to or greater than that by cells from animals given control diet. Blast cells recovered from 48-hr concanavalin A stimulated spleen cell cultures from ethanol-treated animals, however, showed a decreased ability to proliferate in response to exogenous interleukin-2. Binding of 125I-interleukin-2 to blast cells resulting from concanavalin A stimulation, under conditions that detected high-affinity binding, was similar in cells from treated and control animals. These data indicate that the deficiency in proliferation of lymphocytes from ethanol-treated animals is not caused by a lack of interleukin-2 production by the T cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190492 TI - Plasma tumor necrosis factor alpha predicts decreased long-term survival in severe alcoholic hepatitis. AB - Plasma tumor necrosis factor alpha (TNF alpha), interleukin 1 alpha (IL-1 alpha), and interleukin 1 beta (IL-1 beta) were measured in plasma samples obtained from 23 patients with severe alcoholic hepatitis on admission and after 30 days of hospitalization. Over a 2-year follow-up period, 14 patients died at a mean time of 8 months following discharge. The presence of elevated plasma TNF alpha either at admission or discharge from the hospital was associated with death in 82% (14/17) of patients. By contrast absence of elevated plasma TNF alpha was associated with survival in 100% (6/6). The difference in survival with and without detectable plasma TNF alpha was significant at p = 0.0022. Plasma TNF alpha was not elevated in alcoholic patients without clinically apparent liver disease, with alcoholic cirrhosis, or in nonalcoholic healthy controls. Plasma IL 1 alpha was also significantly increased in alcoholic hepatitis whereas IL-1 beta was not. Neither IL-1 alpha nor beta was correlated with outcome in the alcoholic hepatitis group. It is concluded that the presence of elevated plasma TNF alpha is a significant predictor of decreased long-term survival in patients with severe alcoholic hepatitis. PMID- 2190493 TI - The female alcohol abuser: vulnerability to multiple organ damage. PMID- 2190495 TI - ISBRA/RSA Congress 1990. June 17-22, 1990, Toronto, Canada. Abstracts. PMID- 2190494 TI - Aldehyde dehydrogenases and alcoholism. PMID- 2190496 TI - Bombardment mass spectrometry. PMID- 2190497 TI - Staging equine seminiferous tubules by Nomarski optics in unstained histologic sections and in tubules mounted in toto to reveal the spermatogenic wave. AB - Nomarski optics were used to identify stages of the spermatogenic cycle of seminiferous tubules in sectioned tissue or in whole dispersed tubules and to characterize the equine spermatogenic wave. Embedded tissues were sectioned at 20 microns. Whole dispersed tubules were obtained by enzymatic digestion of thin slices of fresh testis. Dispersed tubules were fixed, dehydrated in graded levels of alcohol, infiltrated with Epon, and mounted in toto on glass slides. Stages of the spermatogenic cycle could be identified under Nomarski optics in both histologic sections and tubules mounted in toto. Stage dependent nuclear chromatic and cytoplasmic changes in spermatogonia, spermatocytes, and spermatids were evident. Spermatid development included chromatin condensation, nuclear elongation, acrosomal development from the Golgi and proacrosomic granules, migration of the annulus and mitochondrial alignment, and the transient appearance of the chromatoid body and manchette. Both nuclear and cytoplasmic details of Sertoli cells were revealed. In tubules mounted in toto, the spermatogenic wave along the length of the tubules occurred as a consecutive set of stages occupying small regions along the tubular length. The spermatogenic wave in the horse is more similar to that of humans than that of rats. The combination of enzymatic isolation of seminiferous tubules and identification of spermatogenic stages by Nomarski optics facilitates examination of the spermatogenic wave in species whose tubules are tightly bound and not easily teased apart. PMID- 2190498 TI - Anatomy of the pancreas and Langerhans islets in snakes and lizards. AB - The pancreas of snakes (18 species) was comparatively examined and classified into five major types, based on structure of the lobes and ducts, spatial relationships with the spleen and the gall bladder, and the disposition of islet cells. These types trend toward fusion of the pancreatic lobes and compaction of the pancreas--a progression that coincides with the phylogeny of the snakes. The more primitive pancreas of lizards (17 species) also was surveyed; that of Varanus is of special interest because its structure is intermediate between the extended, tri-lobate pancreas of lizards and the compact pancreas of snakes and may represent a transitional link in the evolution of this organ. Islet tissue is always confined to the dorsal lobe and is concentrated in its distal region adjacent to the spleen. In primitive snakes and in Varanus, a large islet mass is sequestered within a distinct juxtasplenic "islet body" distanced from the dorsal lobe and connected to it by a slender stalk. In some of the most advanced snake species, numerous islets of endocrine cells are found within the spleen. The occurrence and formation of these intrasplenic islets is described in detail. The anatomic "affinity" between spleen and the islet region of the pancreas is discussed. A hypothesis for the development of the pancreas from embryonal placodes on the mid-gut is presented; it proposes that the exocrine and the endocrine components derive from different progenitor cells, and that the endocrine progenitors are located in the center of the dorsal placode. The hypothesis combines embryological and evolutionary views about the origin of the pancreas, and offers a rationale for differences in its structure and in the disposition of the islets. PMID- 2190499 TI - Idiopathic hypertrophic subaortic stenosis and ischemic mitral regurgitation: the value of intraoperative transesophageal echocardiography and Doppler color flow imaging in guiding operative therapy. PMID- 2190500 TI - Abel Lawrence Peirson on animal magnetism. PMID- 2190501 TI - Reevaluation of hemodynamic consequences of positive pressure ventilation: emphasis on cyclic right ventricular afterloading by mechanical lung inflation. AB - To examine the cyclic changes in right ventricular (RV) function induced by controlled ventilation, right heart catheterization and two-dimensional echocardiography were combined in a group of 20 patients requiring respiratory support for an episode of acute respiratory failure. Simultaneous measurements of RV pressure (using a modified pulmonary artery catheter), RV stroke output (thermodilution), and RV dimensions (two-dimensional echocardiography), permitted a beat to beat evaluation of RV function throughout the mechanical respiratory cycle. When compared with expiration, lung inflation produced an increase in RV systolic pressure and volume, an increase in RV diastolic volume with an unchanged RV diastolic pressure, and a marked decrease in RV ejection fraction. It is concluded that controlled ventilation altered RV function primarily by increasing RV afterload during the lung inflation period. PMID- 2190502 TI - A randomized double-blind comparison of epidural versus intravenous fentanyl infusion for analgesia after cesarean section. AB - The authors conducted a randomized double-blind controlled study comparing groups of patients receiving iv or epidural fentanyl infusions to determine whether, at comparable levels of analgesia, 1) the severity of side effects was different; and 2) plasma fentanyl concentrations differed between the two groups. Twenty eight ASA physical status 2 women scheduled to undergo elective cesarean section were randomized into two groups to either receive fentanyl intravenously and saline epidurally or fentanyl epidurally and saline intravenously. After delivery of the infants under epidural anesthesia, each patient received a bolus of fentanyl 1.5 microgram/kg either intravenously or epidurally, and a fentanyl infusion was begun via the same route. Concurrently, a saline bolus and infusion were given via the alternate route. The rates of the fentanyl and saline infusions were adjusted until each patient was comfortable. Patients rated their pain, nausea, and pruritus on visual analogue scales. Sedation was evaluated by an observer. Respiratory depression was evaluated by end-tidal PCO2. Data were analyzed by unpaired two-tail t tests. Plasma fentanyl concentrations were measured at 12 and 24 h. Three patients in the iv group were dropped from the study because of inadequate pain relief. For the remaining 25 patients, similar infusion rates of fentanyl were required to produce similar levels of analgesia at 12 and 24 h. The severity of nausea, pruritus and sedation, and end-tidal PCO2 were similar for both groups. The plasma concentrations of fentanyl were significantly greater in those who received iv fentanyl at 12 h but not at 24 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190503 TI - [The volume of extravascular lung fluid]. PMID- 2190504 TI - [The hemodynamic changes during preoperative acute normovolemic hemodilution (prospective, randomized and comparative research)]. AB - Fifteen patients examined after preoperative acute normovolemic hemodilution (PANH) up to hematocrit value of 0.30 developed a significant increase in cardiac output (CO) and cardiac index (CI) and a decrease in total peripheral resistance (TPR), other hemodynamic parameters remained unchanged. In normal hemodynamics the patient's age is not a contraindication for PANH. Noninvasive monitoring of hemodynamic parameters, CO, CI and TPR in particular, during surgery employing PANH is obligatory for the early diagnosis and correction of impaired circulation. PMID- 2190505 TI - Why the self is empty. Toward a historically situated psychology. AB - This article presents a contextualized treatment of the current configuration of self, some of the pathologies that plague it, and the technologies that attempt to heal it. Of particular interest is the historical shift from the Victorian, sexually restricted self to the post-World War II empty self. The empty self is soothed and made cohesive by becoming "filled up" with food, consumer products, and celebrities. Its historical antecedents, economic constituents, and political consequences are the focus of this article. The two professions most responsible for healing the empty self, advertising and psychotherapy, find themselves in a bind: They must treat a psychological symptom without being able to address its historical causes. Both circumvent the bind by employing the life-style solution, a strategy that attempts to heal by covertly filling the empty self with the accoutrements, values, and mannerisms of idealized figures. This strategy solves an old problem but creates new ones, including an opportunity for abuse by exploitive therapists, cult leaders, and politicians. Psychology's role in constructing the empty self, and thus reproducing the current hierarchy of power and privilege, is examined. PMID- 2190506 TI - Methacholine airway responsiveness decreases during exercise in asthmatic subjects. AB - In many asthmatic subjects, bronchoconstriction develops 2 to 5 min after exercise, reaches a maximum at approximately 10 min, and declines over the next 60 min. However, bronchodilation is typically observed during and immediately after exercise. We measured the bronchoconstrictor responses to increasing concentrations of inhaled methacholine at rest and during two levels of exercise in seven asthmatic subjects to determine the protection against bronchoconstriction afforded by exercise. On the first day, an incremental Stage 1 exercise test was performed to determine the work capacity (Wcap) of each subject. On the second, third, and fourth days, methacholine was inhaled at rest or during steady-state exercise at one-third or two-thirds of Wcap. The bronchoconstrictor response to methacholine was significantly reduced during exercise (p less than 0.0001). The concentration of methacholine required to produce a 20% reduction in FEV1 (PC20) increased from 2.80 mg/ml (%SEM, 1.62) at rest to 7.29 mg/ml (%SEM, 1.43) during exercise at one-third Wcap, and to 31.03 mg/ml (%SEM, 1.74) during exercise at two-thirds Wcap (p less than 0.001). This study has demonstrated that there is greater than tenfold protection against bronchoconstriction by methacholine during exercise, and the magnitude of the protection depends on the intensity of exercise performed. The mechanism of this protection is not known, but may have clinical utility. PMID- 2190507 TI - Effect of 15-(s)-hydroxyeicosatetraenoic acid on allergen-induced asthmatic responses. AB - 15-(s)-hydroxyeicosatetraenoic acid (15-HETE), a major oxidative metabolite of arachidonic acid in human lungs, has complex actions on the 5-lipoxygenase pathway in different cell systems. We have examined the effect of inhaled 15-HETE on the early and late asthmatic responses (EAR and LAR) and the associated change in nonspecific bronchial responsiveness to inhaled allergen in 10 subjects with atopic asthma. On 2 separate days 3 wk apart, subjects inhaled either 70 nmol 15 HETE or the diluent (sodium phosphate buffer) in a randomized and double-blind fashion, followed by a dose of allergen that had previously been shown to produce a 25% fall in baseline FEV1. Analysis of the area under the FEV1 response time course curves (AUC) in the first hour revealed that preinhalation with 15-HETE increased the EAR by 39% from that achieved after the diluent (p less than 0.05). In the seven subjects who were classified as dual responders by developing a LAR previously (greater than 15% fall in baseline FEV1 3 to 8 h after allergen challenge), 15-HETE did not cause any significant change in the magnitude of the LAR when compared with that observed after placebo. The values of the provocation concentration of histamine causing a 20% fall in FEV1 (Pc20) at 8 h postchallenge were significantly reduced on both study days when compared with the corresponding preallergen challenge values, whether analyzed for the whole group or for the seven dual responders (p less than 0.05). 15-HETE had no effect on this allergen-acquired airway hyperresponsiveness to histamine when compared with the diluent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190508 TI - Coronary flow limits right ventricular performance during positive end-expiratory pressure. AB - The effect of positive end-expiratory pressure (PEEP) on right ventricular performance and myocardial blood flow was determined in 16 dogs before and after right coronary artery (RCA) occlusion. Right ventricular ejection fraction (RVEF), end-diastolic volume (EDV) and end-ejection volume were measured by thermodilution. Right ventricular end-ejection pressure-volume relations (RVEEPVR) were determined at baseline and at 20 cm H2O PEEP, both before and after RCA occlusion. In four of the dogs, RVEEPVR were also determined at 10 cm H2O PEEP after RCA occlusion. With intact RCA flow, RVEF declined with PEEP (37 +/- 5 to 19 +/- 6%) with no significant change in EDV (50 +/- 11 to 42 +/- 11 ml) or end-ejection volume (31 +/- 7 to 36 +/- 9 ml). RVEEPVR and right ventricular myocardial blood flow were also unchanged with PEEP. After RCA occlusion, RVEF declined with PEEP (27 +/- 4 to 15 +/- 5%) in association with a significant increase in end-ejection volume (39 +/- 8 to 49 +/- 10 ml), but no change in EDV (53 to 55 ml). In addition, RVEEPVR and myocardial blood flow declined with RCA occlusion, and declined further with 20 cm H2O, but not with 10 cm H2O PEEP, after RCA occlusion. Therefore, in this experimental model, right ventricular performance was adversely affected during PEEP when right coronary blood flow was limited. PMID- 2190509 TI - Pulmonary infectious complications of human immunodeficiency virus infection. Part II. PMID- 2190510 TI - Carcinoid tumor of the bile duct. A case report and literature review. AB - A 35-year-old woman presented with painless jaundice that on evaluation was attributed to a tumor at the confluence of the hepatic ducts. There was no evidence of tumor spread on preoperative workup. The tumor was resected and histologically was typical for carcinoid. There have been only ten previously described cases of bile duct carcinoid tumors excluding gallbladder and ampullary lesions. This study presents a discussion of the management of these tumors and a review of the literature. PMID- 2190511 TI - Surgical treatment of pleomorphic carcinoma of the pancreas. AB - Pleomorphic carcinoma of the pancreas is a rare malignancy that carries a poor prognosis. This case describes a patient with a pleomorphic carcinoma of the head of the pancreas, cured by a pylorus sparing pancreaticoduodenectomy. The literature is reviewed with emphasis on the surgical cures reported. The giant cell variety of pleomorphic carcinoma may carry a better prognosis. Pleomorphic histology of pancreatic neoplasms is not a contraindication for surgical resection. PMID- 2190512 TI - Malignant melanoma metastatic to the gallbladder. Case report and review of the literature. AB - A case of melanoma metastatic to the gallbladder is presented with review of the literature. Currently, there are 20 cases reported that have presented with acute and/or chronic cholecystitis. Ultrasonographic findings of an echogenic mass within the gallbladder without the accompanying acoustic shadowing can be diagnostic in a patient with a history of melanoma. The presence of tumor cells within the bile recovered from the common bile duct suggests the possibility of drop metastasis as a mechanism of spread to the common bile duct and the small intestine. The difficulties in distinguishing primary from secondary melanoma of the gallbladder are discussed. PMID- 2190513 TI - Choledochal cyst. A case report. AB - Choledochal cyst is an unusual entity that has increasingly been encountered by ultrasound and computed tomography (CT) scan. The symptoms are variable and the recommended treatment is surgical excision. PMID- 2190514 TI - Are corticosteroids beneficial as adjunctive therapy for Pneumocystis pneumonia in AIDS? PMID- 2190515 TI - Corticosteroids prevent early deterioration in patients with moderately severe Pneumocystis carinii pneumonia and the acquired immunodeficiency syndrome (AIDS) AB - OBJECTIVE: To determine whether oral corticosteroids can prevent early deterioration in patients with acquired immunodeficiency syndrome (AIDS)-related Pneumocystis carinii pneumonia. DESIGN: Prospective, double-blind, placebo controlled, randomized trial. METHODS: Included patients were having their first P. carinii pneumonia episode, had no other known active pulmonary pathology, had no contraindications for corticosteroids, received no anti-P. carinii pneumonia medications for more than 48 hours, and had oxygen saturation by pulse oximetry of 85% or more and less than 90% at rest or a 5-percentage-point decrease in oxygen saturation with exercise while breathing room air. Consenting subjects were randomly assigned to prednisone, 60 mg/d for 7 days, followed by a progressive tapering over 14 days or to an identical placebo. Early deterioration, the endpoint of the trial, was defined as a 10% decrease in baseline oxygen saturation on day 3 or thereafter. The cases of patients developing early deterioration were considered to be failures of treatment; the code was then broken, and the patient's treatment was left to the judgment of the treating physician. Sequential analysis was done with the primary variable being development of early deterioration. RESULTS: The trial was terminated 5 April 1989 on the basis of the sequential analysis when a total of nine episodes of early deterioration had occurred in the first 37 patients at an overall significance level of P = 0.0136. A total of 8 of 19 placebo-treated patients (42.1%) developed early deterioration compared with only 1 of 18 patients (5.6%) treated with corticosteroids. Baseline characteristics were not statistically different between the two treatment groups. The adjusted odds ratio for the treatment effect was 5.87 (95% CI, 1.27 to 27.4). The adjusted point estimates for the probability of early deterioration in the placebo and corticosteroid groups were 43% and 12%, respectively. All 8 patients in the placebo group developing early deterioration recovered rapidly with addition of corticosteroid treatment. The single patient with early deterioration in the corticosteroid group died on day 6 from overwhelming P. carinii pneumonia, as documented at autopsy. The corticosteroid group had an increased exercise tolerance on day 7 that persisted at day 30. CONCLUSION: Oral corticosteroids prevent early deterioration and increase exercise tolerance in patients with moderately severe AIDS-related P. carinii pneumonia. PMID- 2190516 TI - Erythromycin for persistent or recurrent nongonococcal urethritis. A randomized, placebo-controlled trial. AB - OBJECTIVE: To evaluate the efficacy of a 3-week regimen of erythromycin for treatment of persistent or recurrent nongonococcal urethritis in men. DESIGN: A prospective, randomized, double-blind trial with follow-up at 2, 4, and 8 weeks after enrollment. PATIENTS: Seventy-seven evaluable men with objective evidence of nongonococcal urethritis (36 in the erythromycin group and 41 in the placebo group) with a mean age of 28 years, a median duration of urethritis of 3 months, and a median number of three previous antimicrobial regimens. INTERVENTION: Erythromycin, 500 mg, or placebo four times daily for 3 weeks. RESULTS: After 2 weeks of treatment, urethral symptoms resolved in 13 of 25 erythromycin-treated patients compared with 8 of 34 placebo-treated patients (P = 0.03). Erythromycin also resulted in more frequent resolution of urethral discharge and leukocytosis at all visits compared with placebo but these differences were not statistically significant. First-voided urine leukocyte counts decreased, however, by a median of 89% (95% CI, -96% to -67%) in the erythromycin group compared with 23% (CI, 73% to 83%) in the placebo group after treatment (P = 0.02 for the difference in changes). Further, in men with prostatic inflammation, urinary leukocyte counts decreased by a median of 94% (CI, -99% to -83%) after treatment in erythromycin treated patients compared with a 46% increase (CI, -57% to 290%) in placebo treated patients (P = 0.0003 for the difference in changes). CONCLUSION: A 3-week regimen of erythromycin was more effective than placebo in improving symptoms and in reducing pyuria in men with persistent or recurrent nongonococcal urethritis, especially among men with prostatic inflammation. PMID- 2190517 TI - Use of ambulatory electrocardiographic (Holter) monitoring. AB - PURPOSE: To evaluate the clinical efficacy of ambulatory electrocardiographic (ECG) monitoring and to develop guidelines for its use in clinical practice. DATA IDENTIFICATION: Studies reported since January 1978 were identified both through computer searches using Index Medicus and extensive manual searching of bibliographies of identified articles. STUDY SELECTION: Only studies that fulfilled methodologic criteria designed to limit bias were reviewed. DATA EXTRACTION: Information describing population and study results was assessed in four major categories (variability, diagnosis, prognosis, and therapy guidance) for both arrhythmia monitoring and ST-segment analysis. RESULTS OF DATA ANALYSIS: The day-to-day variability of arrhythmia and myocardial ischemia detected by ambulatory ECG monitoring may be considerable in an individual patient. Caution must therefore be used in interpreting serial tests. Ambulatory ECG monitoring with diary correlation permits documentation of cardiac arrhythmias causing symptoms, but the diagnostic yield is low unless symptoms are frequent. Such monitoring can provide information about prognosis in patients after acute myocardial infarction. The amount of prognostic information obtained is modest and is outweighed by other measures. There is insufficient information to make conclusions about such monitoring and prognosis in other conditions. Serial ambulatory ECG monitoring may be used to assess the effect of an antiarrhythmic drug in patients with frequent and reproducible ventricular ectopy. The effect of arrhythmia suppression on survival is uncertain. Because of its low sensitivity and specificity, analysis of ST-segment changes during ambulatory ECG monitoring is inaccurate in establishing or excluding the presence of coronary disease. Although anti-ischemic interventions reduce the frequency and duration of ST segment changes on monitoring, there are no data on the utility of using reduction or elimination of the changes as the endpoint of therapy. CONCLUSIONS: Ambulatory ECG monitoring can provide diagnostic, prognostic, and therapeutic information in many situations, but similar information often may be better obtained in other ways. PMID- 2190518 TI - More informative abstracts revisited. AB - Following proposals in 1987 and 1988, several medical journals have provided more informative abstracts ("structured abstracts") for articles of clinical interest. Structured abstracts for original studies require authors to systematically disclose the objective, basic research design, clinical setting, participants, interventions (if any), main outcome measurements, results, and conclusions; and for literature reviews the objective, data sources, methods of study selection, data extraction and synthesis, and conclusions. More informative abstracts of this kind can facilitate peer review before publication, assist clinical readers to find articles that are both scientifically sound and applicable to their practices, and allow more precise computerized literature searches. We review the feasibility, acceptability, and dissemination of structured abstracts, reassess the underlying strategy, and describe modifications of the approach. This innovation can aid communication from scientists to clinicians, and other clinical journals are invited to join this effort. PMID- 2190519 TI - Diagnosis of deep-vein thrombosis using an objective Doppler method. AB - STUDY OBJECTIVE: To determine the diagnostic criteria (phase I) and to assess the accuracy (phase II) of an objective Doppler-Valsalva pressure method as compared with contrast venography for the diagnosis of acute deep-leg-vein thrombosis in symptomatic outpatients. DESIGN: A two-phase prospective study in consecutive patients. Doppler ultrasound strip-chart recordings and venograms were independently analyzed by experienced observers. SETTING: Referral-based medical clinics at university medical centers. PATIENTS: One hundred and ten (phase I) and one hundred and fifty-five (phase II) patients who had clinically suspected venous thrombosis and were referred by their general practitioners were included. METHODS AND MEASUREMENTS: A normal Doppler test result was defined as a cyclic spontaneous signal (S-signal), a continuous S-signal with a Valsalva pressure of less than 6.5 mm Hg, or an absent S-signal with flow after cessation of the Valsalva maneuver. A continuous S-signal with a Valsalva pressure of 6.5 mm Hg or more or an absent S-signal without flow after cessation of the Valsalva maneuver were defined as abnormal test results. The accuracy indices for proximal vein thrombosis in phase II (155 patients; prevalence, 31%) were sensitivity, 91% (95% CI, 79% to 98%), and specificity, 99% (CI, 97% to 100%). All 3 patients with isolated calf-vein thrombosis had normal Doppler test results. CONCLUSIONS: The objective Doppler method is an accurate, reproducible, and simple method for detection of venous thrombosis in symptomatic outpatients. PMID- 2190520 TI - [Hyperinsulinism syndromes caused by insulin resistance]. AB - Resistance to insulin consists in a decrease in insulin's biologic action and is manifested mainly by hyperinsulinism. Clinical investigation of insulin resistance states relies on specialized tests, performed both in vitro and in vivo. The hyperinsulinemic-euglycemic clamp is the reference method for quantifying insulin resistance and can differentiate decreased insulin sensitivity and decreased maximal capacity for glucose uptake. Glucose flux measurements, using glucose labelled with stable isotopes, distinguish hepatic and peripheral factors involved in insulin resistance. In vitro studies include investigations for antibodies against insulin and insulin receptors, studies of insulin receptors and their tyrosine kinase activity, and studies of postreceptor cell metabolism. These investigations are especially useful in genetic syndromes of extreme insulin resistance, whose pathophysiology is largely unelucidated, including: insulin resistance syndromes with acanthosis nigricans, obesity acanthosis nigricans-hyperandrogenism syndrome, lipoatrophic diabetes, leprechaunism, and other syndromes. But insulin resistance also plays a major role in non-insulin-dependent diabetes mellitus, insulin-dependent diabetes mellitus, and various pathological or even physiological endocrine alterations. PMID- 2190521 TI - [Joubert's syndrome]. AB - We report a new case of pathologically documented Joubert syndrome. A review of 35 published cases showed that this syndrome, first described by Joubert and Eisenring in 1969, is well individualized and exhibits consistent features, including attacks of tachypnea alternating with respiratory pauses, abnormal ocular movements, severe psychomotor retardation, and ataxia. Anatomic anomalies include vermian agenesis with cystic dilatation of the fourth ventricle. Inheritance of this condition is autosomal and recessive. Onset is in the neonatal period and prognosis is severe. Significant anatomic resemblances with the Dandy-Walker syndrome exist, although genetic and clinical features are different. The origin of this syndrome is unknown, but a study of peroxisomes is required since three cases of Joubert syndrome with pipecolic acidemia have been reported and resemblances exist between some recognized peroxisomal diseases and Joubert syndrome. PMID- 2190522 TI - [Knee arthritis caused by Eikenella corrodens. Apropos of a case]. AB - We report a case of septic arthritis of the knee following an articular wound caused by a bite in a previously healthy 8-year-old girl. The causative agent was Eikenella corrodens, an opportunistic bacteria that is normally part of the commensal flora of the oral cavity. We point out that Eikenella corrodens may cause severe complications in healthy subjects and emphasize the need for considering this organism not only in infections of the hands, face and neck, but also after bites. Penicillins are consistently effective and constitute the treatment of choice. PMID- 2190523 TI - [Epidemiology of congenital malaria in the urban milieu of Kinshasa (Zaire)]. AB - Thick blood films for detection of hematozoa were routinely performed in 953 neonates and their mothers within 12 hours of delivery. Hematozoa were found in 4% of neonates and 13% of mothers. Positive tests were found in 19 neonates born to mothers with negative tests. Mean birth weight was 3,166 g in infected neonates and 3,171 g in uninfected neonates, suggesting that congenital malaria has no effect on birth weight. PMID- 2190524 TI - [Sexual identity disorders in children]. PMID- 2190525 TI - The fate of soluble steroids within breast prostheses in humans. AB - The long-term fate of 6-alpha-methyl-methylprednisolone hemisuccinate (MPHS) placed into breast prostheses prior to implantation in humans was determined. MPHS hydrolyzes to the active form 6-alpha-methylprednisolone (MP) in water, which then diffuses out of the implant. Twenty prostheses were recovered 5.3 to 34.7 months after placement, and the solution inside was analyzed for MPHS and MP. Half-lives were calculated for the hydrolysis of MPHS to MP (3.4 +/- 0.58 months [mean +/- SEM]) and for the diffusion of MP out of the prostheses (20.63 +/- 6.10 months). The large half-lives found imply that MPHS slowly hydrolyzes to MP, and that active steroid is released for a longer time than was previously thought. This long release could be the cause of the long-term effects seen with steroids used in this manner. PMID- 2190526 TI - Oncogenesis by mutations in anti-oncogenes: a view. AB - Oncogenesis is the result of accumulation of specific gene mutations. Two classes of specific cancer mutations are distinguished: namely those affecting anti oncogenes and those in which oncogenes are involved. Anti-oncogenes are thought to regulate normal growth by encoding proteins that inhibit the expression of the oncogenes. This is in line with the observation that tumor cells are often homozygous for a defect in an anti-oncogene, as this will allow the expression of an oncogene. In this paper we attempt to calculate the number of anti-oncogenes involved in the genesis of a malignant tumour cell. These calculations were initially performed using a simplified model for oncogenesis and later applied to more complicated situations. These calculations indicate that usually four mutations in anti-oncogenes are required for oncogenesis in adults. This is in contradiction to the well-known 2-hit model of oncogenesis of Knudson which predicts about 10(9) times more de novo arising tumour cells than are observed in reality. Oncogenesis is only observed in proliferating cells. Cell proliferation and growth kinetics in various organs differ greatly. Therefore the time of oncogenesis and tumour manifestation also varies in the different organs. In organs that develop in early life (e.g. retina and neurons of the brain) mitotic activity ceases soon after birth. Consequently neural and retinal tumours emerge only early in life. In contrast, the main development of the female breast occurs after puberty, and the earliest breast tumours will become apparent in young adults. The four recessive mutations in anti-oncogenes required for oncogenesis imply that probably recessive mutations are involved in two loci. It is clear that an inherited mutation in an anti-oncogene at a particular locus causes different tumour types depending on the various organs in which the tumours arise. Comparison of (a) results of calculations about the number of malignant neuroendocrine tumour cells that arise in a pancreatic islet of a patient with inherited MEN1-syndrome with (b) the pathological anatomy of such a patient, suggests that a cell with two or three oncogenic mutations has a growth advantage over normal cells. This leads to cell proliferation in a premalignant lesion until the set of four oncogenic mutations is complete. The clinically premalignant lesions have a maximal mean diameter of about 0.4 cm when the first true malignant tumour cell develops, and the pathologist will probably note malignancy when the lesion has the size of 1-2 cm.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2190527 TI - Hereditary cancer and its clinical implications: a view. AB - In hereditary cancers the responsible inherited cancer genes are defective (mutated) anti-oncogenes (tumour suppressor genes). This inherited mutation is present in all cells of the organism, and only leads to cancer if in a somatic cell a complete set of specific cancer mutations is accumulated. Since one defective anti-oncogene has been inherited, only three additional somatic cancer mutations are required, according to our previously published view (Anticancer Res 10:1990). The number of de novo arising tumour cells in such a person is thus multiplied by a factor equal to the reverse of the mutant frequency, that is about 10(4)-10(5). This can be observed e.g. in retinoblastoma. Mutations occur in proliferating cells only. Consequently cancer mutations also depend on cell proliferation. If an inherited cancer mutation predisposes to cancer formation in certain organs, then the cancer risk in these organs is enhanced by 10(4)-10(5) times. Tumours in these organs will appear simultaneously if the number of cells and the growth kinetics are similar. This is of course observed in paired organs, like the retina and the female breast. In cancer family syndromes different organs may be affected at the same time. Examples are type I and type II cancer family syndrome and multiple endocrine neoplasia type 1 2a, and 2b. The secondly diagnosed tumours are not caused by metastatic spread. Tumours in two organs will arise at difference times if the number of end cells per organ and the growth kinetics differ. In this case the second tumour is called a second primary malignancy and is not caused by metastatic spread. A good example are the second primary malignancies in hereditary retinoblastoma. The inherited defective anti oncogene is a recessive gene. This defective inherited gene causes a 10(4)-10(5) fold increase of the normal tumour incidence. This means that nearly always one or more tumours will arise. Evidently, this pattern of inheritance has led to the erroneous conclusion that the genetic abnormality is dominant at the level of the chromosome. The 10(4)-10(5) times enhanced tumour incidence in hereditary cancer is helpful for the clinical recognition of hereditary cancer. That is, hereditary cancer can be recognized not only by family history, but also by early occurrence, the multifocal and bilateral localisation, its occurrence as cancer family syndrome or by second primary malignancies. It is thus recommended to screen patients and families with hereditary cancer for first and second primary tumours. Treatment of patients with hereditary tumours requires extra care to avoid additional cancer mutations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2190528 TI - Dominant inheritance in human cancer. AB - Familial aggregations of defined malignancies are of great importance for determining the genetic factors involved, as has been demonstrated for familial and sporadic retinoblastoma. In nearly all organs, neoplasms occur that are inherited similar to familial retinoblastoma (Rb). For example, more than 5% of all women suffering from breast cancer belong to breast cancer families in which the occurrence of the malignancy suggests an autosomal dominant pattern of inheritance. Familial colon cancer is associated with several well-known autosomal dominantly inherited polyposis syndromes, and also other susceptibilities without obvious clinical features. Site-specific cancers are often accompanied by other malignancies. In addition, there seem to be predispositions to a wider range of different, but well-defined neoplasms: e.g., adenocarcinomatosis of the colon and the endometrium, or the Li-Fraumeni/SBLA syndrome. The latter shows a spectrum of sarcoma, brain tumours, breast cancer, leukaemias, lung and adenocortical cancer. The genes leading to these types of dominantly inherited predispositions appear to be the tentatively so-called tumour suppressor genes, for which the Rb gene serves as a model. It manifests itself recessively on the level of the individual cell, which means both alleles must be deleted or inactivated before a retinoblast develops into a neoplastic cell. Clinical, epidemiological and molecular genetic studies have yet to establish whether the Rb model can be extended to all other forms of dominantly inherited human cancers. PMID- 2190529 TI - Recessively inherited deficiencies predisposing to cancer. AB - The genetic factors involved in the multistep process of carcinogenesis can be divided at least into two major categories: 1. Mutated or lost genes, which may directly represent one step in the sequential process (tumour suppressor genes); inheritance of one tumour suppressor gene causes dominant expression of the carcinogenic phenotype (the dominant inheritance is described in the accompanying paper); 2. Other genes, which lead to conditions that favour the development of cancer and generally are inherited in a recessive fashion; they are the subject of this paper. Autosomal recessively inherited diseases, such as xeroderma pigmentosum, ataxia-telangiectasia, Bloom's syndrome and Fanconi's anaemia display increased genome instability (chromosomal fragility and/or DNA-repair deficiencies) and are associated in the homozygote and probably also in the heterozygote state with defined malignancies. Neoplasms particularly of the lymphoreticular system frequently occur in patients with genetically determined immunodeficiencies (e.g. severe combined immune deficiency or Wiskott-Aldrich syndrome). People differ due to their individual genetic constitution in their responses to various classes of carcinogens such as physical and chemical agents, to dietary habits, as well as to viruses. Furthermore, tumours are often found in patients displaying premature aging (e.g. Werner's syndrome). In addition, several metabolic abnormalities such as genetic syndromes featuring chronic liver disease, but also many other inherited metabolic conditions have cancer as a regular or frequent complication. PMID- 2190530 TI - The molecular biology of acute lymphoblastic leukemia (review). AB - The emergence of molecular and cytogenetic correlates has opened exciting avenues to a better understanding of acute lymphocytic leukemia (ALL) and in turn has sharpened the clinician's ability for classification and treatment. While the pathophysiology and etiology of ALL remains vague, the clinical significance of the chromosomal abnormalities in the pathogenesis of malignant transformation is becoming clearer. This review highlights recent achievements in the genetic research of ALL and discusses the epidemiology, clinical features, and therapeutic determinants of this hematopoietic malignancy. Special attention is given to individual chromosomal abnormalities established by a number of international conferences on chromosomes of adult and childhood ALL. Specifically, model number of chromosomes and structural alterations including t(8;14), t(9;22), t(4;11), 14q+, 6q-, t(11;14) and others are considered in detail. The molecular basis of ALL and the pathogenetic role for genes located near chromosomal breakpoints are discussed in detail. PMID- 2190531 TI - [The Devine urethroplasty. Our experiences apropos of 18 cases]. AB - Our experience with a 1-stage procedure using free patch graft for correction or urethral stricture is reported. Eighteen cases of urethral stricture have been treated. Fourteen of the 18 cases (77%) had a good result. The follow up is more than 5 years. This procedure is recommended with considerable enthusiasm. PMID- 2190532 TI - [Chemotherapy in cancer of the prostate]. AB - The most classical treatment of metastatic prostatic adenocarcinoma is hormone therapy. Most often, chemotherapy is proposed only when the tumor becomes hormonally unresponsive. But evaluation of its efficacy is impaired by the diversity of inclusion criteria used and by the different criteria of response assessment. Results of randomized, comparative studies show that all cytotoxic agents currently available have a similar response rate (about 30 to 40%). Use of combined chemotherapy does not seem to significantly improve these results. Several others ways have been proposed which attempt to improve the efficacy of chemotherapy (androgen stimulation, priming chemotherapy, adjuvant or neo adjuvant chemotherapy...) but, most probably, progress will come from the discovery of more effective and selective cytotoxic agents, and not from the increase of clinical trials with the same agents. PMID- 2190533 TI - 3T3-L1 adipocyte glucose transporter (HepG2 class): sequence and regulation of protein and mRNA expression by insulin, differentiation, and glucose starvation. AB - A glucose transporter cDNA (GLUT) clone was isolated from mouse 3T3-L1 adipocytes and sequenced. The nucleotide and deduced amino acid sequences were, respectively, 95 and 99% homologous to those of the rat brain transporter. The mouse cDNA and a polyclonal antibody recognizing the corresponding in vitro translation product were used to compare changes in transporter mRNA and protein levels during differentiation, glucose starvation, and chronic insulin exposure of 3T3-L1 preadipocytes. The respective cellular content of transporter mRNA and protein were increased 6.6- and 7.8-fold during differentiation, and 3.8- and 2.5 fold from chronic insulin exposure of differentiated adipocytes. Glucose starvation increased transporter mRNA and protein levels 2.2- and 3.5-fold in undifferentiated preadipocytes and 1.8- and 3.1-fold in differentiated adipocytes. Starvation of undifferentiated cells completely converted the native transporter to an incompletely glycosylated form, while increasing basal transport rates 4.5-fold. Either full glycosylation is not required to produce a functionally active transporter, or starvation causes a unique predifferentiation induction of the normally absent "responsive" transporter. The changes in transporter protein expression elicited by differentiation were attributed primarily to increased rates of transporter synthesis, while the disproportionate changes in mRNA and protein expression from chronic insulin treatment and starvation suggested these conditions increase synthesis and decrease turnover rates in regulating transporter protein expression. Although chronic insulin exposure and glucose starvation each raised the expression of transporter protein greater than 3-fold and basal transport rates 2.5- to 4.5-fold, no significant increase in the insulin responsiveness of 3T3-L1 preadipocytes or differentiated adipocytes was observed. Thus, the changes in the transporter mRNA and protein expression observed in this study were most consistent with their being associated with the regulated expression of a basal or low level insulin responsive transporter. PMID- 2190534 TI - Multiple sites of methyl esterification of calmodulin in intact human erythrocytes. AB - Aspartyl and asparaginyl residues are susceptible to spontaneous chemical degradation reactions that result in the formation of isomerized and racemized aspartyl residues. At least a subset of these abnormal residues are recognized by a widely distributed protein D-aspartyl/L-isoaspartyl methyltransferase (EC 2.1.1.77) that can participate in their conversion to normal L-aspartyl residues. We have used this methyltransferase as a probe to identify modified aspartyl and asparaginyl residues in peptides and proteins. In purified calmodulin from bovine brain, major sites of methylation were found to originate from the Asp-2 residue near the amino terminus and the Asp-78 residue in the alpha-helix that connects the two globular calcium-binding domains. When purified calmodulin was incubated at physiological temperature and pH in the absence of calcium, additional methylation sites were found in three of the four calcium-binding sites. In this work we have analyzed the methyl esterification of human calmodulin catalyzed by this enzyme in intact erythrocytes. On the basis of results from peptide mapping studies, Asp-2, Asp-78/80, and residues in calcium-binding domains III and IV appear to be methylated. Methylation of sites in the calcium-binding regions appears to reflect the low concentration of free calcium in human erythrocytes. We also found that calmodulin isolated from erythrocytes and methylated in vitro contains major methylation sites at Asp-2 and Asp-78/80 but not in the calcium binding sites. Comparison of the number of available methylation sites of calmodulin in intact cells and in material aged in vitro supports the hypothesis that repair processes can occur in erythrocytes. PMID- 2190535 TI - C-terminal cleavage of tubulin by subtilisin enhances ring formation. AB - Following cleavage of alpha- and beta-tubulin C termini, under mild conditions we observed that microtubule-related polymers were formed, and also that ring aggregates were abundant. These ring aggregates were clearly detected by turbidity and electron microscope studies under standard assembly conditions. It was found that removal of the C-terminal fragments of tubulin (phosphocellulose tubulin or Weisenberg tubulin) markedly favored Mg2(+)-induced ring formation. Binding of GDP to the exchangeable nucleotide site of cleaved tubulin further enhanced ring formation. The cleaved tubulin-GDP ring aggregates could be classified into three types: aggregates without apparent order, bidimensionally ordered ring aggregates, and stacks of rings. Temperature had little effect on the formation of these ring aggregates; however, they were very sensitive to ionic strength. PMID- 2190536 TI - [Progress of research on xeroderma pigmentosum]. AB - Xeroderma pigmentosum (XP) is an autosomal recessive human disease, clinically characterized by high incidence of skin cancers on sun-exposed areas. XP cells are hypersensitive to killing by ultraviolet light (UV), because they have a defect in DNA excision repair of UV-induced DNA damages. Genetic complementation analysis by cell fusion has identified 9 genetic complementation groups, designated groups A through H and a variant. However, the genetic basis of the physiological defect of XP has not yet been characterized. Recently, XP genes and human DNA repair genes have been molecularly cloned by DNA transfection methods. Molecular biological analysis of these genes should be a clue to elucidating the molecular mechanism of DNA repair in human. Moreover, an in vivo microinjection system and an in vitro system for study of DNA repair synthesis promoted by human cell extract have been developed and they can be utilized as assays during the purification of protein factors that complement repair defective XP cells. A nuclear factor that binds to DNA lesion has been identified and it was defective in group E XP cells. Yeast homolog of this nuclear factor appears to be a photolyase. PMID- 2190537 TI - [Efficacy of Cepharanthin for preventing leukopenia and thrombocytopenia induced by chemotherapy in breast cancer patient--prospective randomized study]. AB - A prospective randomized study was carried out to evaluate the efficacy of Cepharanthin (CEP) on leukocytopenia and thrombocytopenia during chemotherapy in breast cancer patients. The CEP group (51 patients) was administered CEP by 60 mg/day p.o.. The control group (55 patients) was not administered CEP in all the times. The rate of leukocytopenia was significantly lower (p less than 0.05) in the CEP group than in the control. But the recovery periods from nadir to normal range in WBC were not significantly different between the two groups. The average of nadir of WBC in the leukocytopenia patients was higher in the CEP group than in the control, but it was not significant. In MMVC group and MMC + TAM group, the rate of leukocytopenia was significantly lower in the CEP group than in the controls. The obvious efficacy of CEP for thrombocytopenia was not obtained in this study. We conclude that CEP showed an efficacy on preventing leukocytopenia induced by chemotherapy in breast cancer patients. PMID- 2190538 TI - [Fatigue-induced unsafe driving by occupational drivers. Criminologic knowledge and legal consequences]. PMID- 2190539 TI - SCAN. Schedules for Clinical Assessment in Neuropsychiatry. AB - After more than 12 years of development, the ninth edition of the Present State Examination (PSE-9) was published, together with associated instruments and computer algorithm, in 1974. The system has now been expanded, in the framework of the World Health Organization/Alcohol, Drug Abuse, and Mental Health Administration Joint Project on Standardization of Diagnosis and Classification, and is being tested with the aim of developing a comprehensive procedure for clinical examination that is also capable of generating many of the categories of the International Classification of Diseases, 10th edition, and the Diagnostic and Statistical Manual of Mental Disorders, revised third edition. The new system is known as SCAN (Schedules for Clinical Assessment in Neuropsychiatry). It includes the 10th edition of the PSE as one of its core schedules, preliminary tests of which have suggested that reliability is similar to that of PSE-9. SCAN is being field tested in 20 centers in 11 countries. A final version is expected to be available in January 1990. PMID- 2190540 TI - Nuclear aberrations in hair follicle cells of patients receiving cyclophosphamide. A possible in vivo assay for human exposure to genotoxic agents. AB - The toxic effect of cyclophosphamide on the proliferative cell population of hair follicles plucked from the human scalp was examined by the in vivo nuclear aberration assay. Patients participating in an independent clinical trial received oral low dose cyclophosphamide, intravenous high dose cyclophosphamide or oral placebo treatment. The percent of cells with nuclear aberrations (indicating apoptosis, a special form of cell death) and the percent of mitotic cells, in the hair matrix, were calculated for each patient before treatment and at several time points following cyclophosphamide or placebo treatment. The mean percentages of nuclear aberrations in both the treated Low dose and High dose cyclophosphamide patients were significantly higher than those for the pre treatment and Placebo patients. The nuclear aberrations in hair follicle cells increased from pre-treatment (and Placebo) to treated Low dose and finally to treated High dose patients. The average percentage for pre-treatment samples from all patients was 0.06 +/- 0.03 SE. For 1 week and 1 month samples from Low dose patients it was 0.35 +/- 0.08 SE, and for combined 2,3 and 4 day samples from High dose patients it was 1.08 +/- 0.12 SE. Cyclophosphamide also had a significant effect on mitosis. A decrease in mitotic activity was observed at 1 month following the initial low dose cyclophosphamide treatment and at 24 +/- 2 h following each of the first two high dose cyclophosphamide treatments. The observed increase in nuclear aberrations following low dose as well as high dose cyclophosphamide suggests that it is feasible to use the nuclear aberration assay for in vivo human genotoxicity testing, using proliferating hair follicle cells. PMID- 2190541 TI - [Atopic dermatitis: current problems with diagnosis]. PMID- 2190542 TI - [Gennadii Mikhailovich Pavlov (on the centenary of his birth)]. PMID- 2190543 TI - Portable closed loop feedback system for control of the blood glucose level in the pig. AB - To establish the difference in glucose consumption of healthy compared to diabetic pigs, a transportable system for the feedback control of insulin and glucose was used in conscious pigs. The system for controlling glucose levels, as well as glucose consumption, was easy to use and adjusted smoothly to rapid changes in insulin level. Five days prior to the first day of experiment, healthy animals were prepared with intravenous jugular catheters tunnelled subcutaneously to the neck. On the first day of experiment, measurements of glucose were continuously taken before and after food ingestion. The animals were rendered diabetic after 2 days using Alloxan and streptozotocin. The measurements were then repeated. To be able to obtain constant glucose levels of approximately 3 mmol during both fasting and postprandial periods requires only small glucose adjustment infusion in the diabetic pigs, as opposed to healthy ones. Using the described system, it would be possible to evaluate subclinical diabetes and control unstable diabetics with different therapeutic regimes. PMID- 2190544 TI - Effects of Bacteroides gingivalis culture products on human polymorphonuclear leucocyte morphology. AB - This study aimed to determine whether leucocytes exposed to Bacteroides gingivalis culture supernatant exhibited consistent morphological changes and whether measurement of such changes could provide a simple screening assay for bacterial products with potential biological activity. Glass-adherent polymorphonuclear leucocytes were obtained from clotted blood preparations and from blood after purification by centrifugation through Ficoll-Hypaque. These were then incubated in Hanks' balanced salt solution, a sterile liquid medium (BM) and B. gingivalis (W83) culture supernatant. Polymorphonuclear leucocytes were classified by their shape into small non-polar (less than 18 microns diameter), large non-polar (greater than or equal to 18 microns diameter), bipolar and hyperpolar types. Treatment with B. gingivalis culture supernatant consistently increased large non-polar cells by 150% to over 300% (p less than 0.01), when compared with polymorphonuclear leucocytes incubated with the sterile liquid medium (control). This change was accompanied by smaller decreases in small non-polar, bipolar and hyperpolar cells, these being significant for bipolar cells in clot preparations (p less than 0.01) and small non-polar cells after Ficoll-Hypaque isolation (p less than 0.01). Neither the liquid medium nor the B. gingivalis culture supernatant was toxic to the cells as indicated by trypan blue exclusion tests. Lipopolysaccharide and short-chain fatty acids were not responsible for the changes in polymorphonuclear leucocyte shape. However, the activity of the culture supernatant was destroyed by heating at 80 degrees C for 30 min, indicating that proteolytic enzymes may have been involved. PMID- 2190545 TI - Free amino acid levels in oral fluids of normal subjects and patients with periodontal disease. AB - The content of free amino acids in submandibular, parotid and whole saliva and in gingival fluid was measured by automatic analyser in patients with progressive periodontitis and in controls. The concentration of individual amino acids showed considerable variation in all the fluids. Two amino acids, proline and delta aminovaleric acid, were never found in gingival fluid or in submandibular and parotid saliva, although detectable in whole saliva. Thus, these amino acids must appear in whole saliva as a result of bacterial metabolism or by degradation of salivary proteins rich in proline. The free amino acid levels in whole saliva did not reflect those of any of the single oral fluids analysed, further stressing the importance of bacterial metabolism as a cause of the wide range of amino acid concentrations. Because of the multifactorial origin of these free amino acids, their determination in oral fluids is of no practical diagnostic value except perhaps in extreme cases. PMID- 2190546 TI - Herpes zoster optic neuritis in human immunodeficiency virus infection. PMID- 2190547 TI - MK-927, a topical carbonic anhydrase inhibitor. Dose response and reproducibility. AB - We investigated the dose-response and reproducibility of the intraocular pressure lowering effect of MK-927 in ocular hypertensive patients. Patients were enrolled until at least 8 "marked responders" (peak reduction in intraocular pressure comparing the MK-927-treated eye with the placebo-treated eye greater than or equal to 6 mm Hg) and 7 "mild responders" (peak reduction in intraocular pressure comparing the MK-927-treated eye with the placebo-treated eye less than or equal to 3 mm Hg) were identified. In part A, 27 patients received one drop of 2% MK 927 in one eye (baseline mean +/- SEM intraocular pressure, 28.0 +/- 1.0 mm Hg) and placebo in the contralateral eye. Intraocular pressure was measured at baseline and 1, 2, 3, 4, and 6 hours. Maximum reduction in intraocular pressure was 4.0 +/- 0.8 mm Hg at 3 hours, with a duration of 4 hours. Ten patients were identified as marked responders and 7 as mild responders. In part B, 8 of the marked responders entered a four-period crossover study and received 2%, 0.5%, and 0.125% MK-927 and placebo in the same treated eye as in part A, and placebo in the contralateral eye. The 7 mild responders in part C received 2% MK-927 in a similar fashion as in part A. MK-927 in concentrations of 0.125% and 0.5% had little or no effect on intraocular pressure in patients with a marked response to 2% MK-927. Within-patient variability in peak response to single doses of 2% MK 927 was substantial (coefficient of variation of 0.3 and 0.5 for marked responder and mild responder groups, respectively. PMID- 2190549 TI - The effect of repeated doses of 30 mg pyridostigmine bromide on pilot performance in an A-4 flight simulator. AB - The effect of repeated doses of 30 mg pyridostigmine bromide every 8 h on flight skills in an A-4 simulator was tested in this crossover double-blind placebo controlled study on 10 pilots experienced in actual and simulated A-4 flights. The pilots flew two test simulator flights 2 h after the fourth dose of pyridostigmine or placebo. The flight profile included navigation, rapid ascent, 360 degrees turns, and instrument landing. Each flight lasted approximately 20 min. Flight parameters measured included indicated air speed, true heading, barometric altitude, vertical velocity, and bank. The mean whole blood cholinesterase inhibition level was 29%. There was no decrement in performance under treatment with pyridostigmine in the percent of deviation time from the prescribed limits or in the average duration or magnitude of the deviation in each of the flight parameters. We conclude that pyridostigmine bromide in repeated doses of 30 mg every 8 h does not appear to influence pilot performance during short A-4 missions. PMID- 2190548 TI - Atropine: effects on glucose metabolism. AB - We have employed the primed constant infusion technique to investigate the metabolic effects of the organophosphate antidote, atropine, on glucose homeostasis in rats. This method utilizes the radioisotopes 6-3H-glucose to measure production and uptake and U-14C-glucose to measure oxidation. Our data indicate that glucose production significantly (p less than 0.05) increased (24.0 +/- 2.0 vs. 30.9 +/- 2.6 mumoles.kg-1.min-1) following atropine administration. The elevated rate of glucose turnover was associated with concomitant increases in glucose oxidation (8.3 +/- 0.6 vs. 12.0 +/- 0.8, mumoles.kg-1.min-1), the percent of glucose uptake oxidized (37.2 +/- 2.0 vs. 44.6 +/- 2.6), and the percent carbon dioxide produced from glucose (8.4 +/- 0.7 vs. 12.0 +/- 1.8). Presumably, these glucokinetic changes were mediated by elevated plasma catecholamines (Epi: 166 +/- 19 vs. 271 +/- 50 pg/ml; Norepi: 262 +/- 24 vs. 525 +/- 63 pg/ml, p less than 0.05) since other glucoregulatory hormones (insulin, glucagon, and corticosterone) were not significantly affected by atropine administration. In addition, there was no change in VO2 associated with atropine administration. These data indicate that atropine enhances glucose production and utilization; such effects could be ergogenic during exercise in thermoneutral conditions. PMID- 2190550 TI - Homeostatic disruption and memory: effect of insulin administration in rats. AB - The present study examined the effect of insulin-induced hypoglycemia on 24-h retention of passive avoidance in rats. In the initial experiment, rats received either insulin (50 U/kg) or saline injections 30 min prior to training and testing. Impairments in retention were observed when animals were trained with insulin and tested with saline. This anterograde memory loss was attenuated, however, when insulin was administered prior to both training and testing. A subsequent experiment further explored the disruptive effect of hypoglycemia on memory. Data from this study indicated that lower doses of insulin at training (5 and 10 U/rat) yielded impairments in 24-h retention of passive avoidance. It is concluded that disruption of glucoregulation can produce state-dependent anterograde memory losses in rats. Possible implications for the effects of hypoglycemia on cognitive functioning in humans are discussed. PMID- 2190552 TI - Induction of haptotactic migration of melanoma cells by neutrophil activating protein/interleukin-8. AB - Natural or recombinant neutrophil activating cytokine (IL-8) induced migration across polycarbonate filters of human A 2058 melanoma cells. Anti-IL-8 antibodies blocked IL-8 induced melanoma cell migration. Checkerboard experiments revealed a gradient-dependent response of A2058 melanoma cells to IL-8. Filters exposed to IL-8 and washed supported melanoma cell migration, thus implying a haptotactic component in the response. The homologous polypeptide platelet factor 4 was inactive. The observation that IL-8 affects melanoma cells emphasizes the need for a comprehensive analysis of the spectrum of action of platelet factor 4 related peptides. The effect of the inflammatory cytokine IL-8 on melanoma cells may be relevant to augmented secondary localization of tumors at sites of inflammation. PMID- 2190553 TI - Raised plasma endothelin-I concentration following cold pressor test. AB - Plasma concentration of immunoreactive endothelin-1 was measured by radioimmunoassay in 6 healthy subjects before and following cold pressor test by immersion of one fore-arm into ice-water. Mean (SEM) plasma endothelin-1 concentration rose from 1.2 (0.7) to peak value 8.4 (2.3) pg/ml in venous plasma from the immersed hand, and, reaching peak 2 minutes later, from 1.4 (0.5) to 4.6 (2.3) pg/ml in venous plasma from the contralateral hand. In 66 healthy control subjects, venous plasma concentration of endothelin-1 was 2.9 +/- 1.2 pg/ml (mean +/- SD). Exposure to cold is associated with raised blood levels of endothelin-1, which points to a relation between endothelin-1 and vasoconstriction associated with low temperature. PMID- 2190551 TI - Physiological hypotheses--intramyocardial pressure. A new concept, suggestions for measurement. AB - Intramyocardial pressure is supposed to play a major role in systolic coronary flow impediment. Via its assumed relation with radial wall stress it is supposed to be similar to ventricular pressure at the endocardium and decreases linearly to negligible values epicardially. Many attempts to measure intramyocardial pressure have been reported in the literature with rather different results. For instance, with most of the various methods, intramyocardial pressures both higher and lower than left ventricular pressure have been obtained and intramyocardial pressures of more than 125 mm Hg have been found in low-loaded isobaric beats (negligible pressure development in systole). In this "physiological hypotheses paper" I suggest left ventricular pressure and intramyocardial pressure both to result from the varying stiffness of cardiac muscle over the heart cycle. For any intramuscular cavity a time varying pressure-volume (P-V) relation results from the changes in muscle stiffness, the so-called time varying elastance defined as E(t) = P(t)/V(t), and with maximal or systolic elastance called Emax. For a constant contractile state the time varying elastance (E(t)) is suggested to be almost independent of preload and afterload. This concept has been well established for the ventricular cavities, but is here proposed to hold for the interstitial space as well. If a cavity is subject to isovolumic conditions the pressure will be high, but when volume in systole decreases (ventricular ejection or squeezing out of interstitial fluid) pressures will be lower. Thus for constant load on the interstitial cavities, but different loads on the ventricle, left ventricular pressure will vary while intramyocardial pressure remains the same. For low-loaded isobaric beats where left ventricular pressure is minimal intramyocardial pressure will remain the same as during normal ventricular loads and isovolumic beats. Augmented contractility will increase Emax and this will increase left ventricular and intramyocardial pressure only by the same amount if loading conditions of both cavities remain the same. Both ventricular pressure and intramyocardial pressure arise from varying stiffness of cardiac muscle and intramyocardial pressure does not result from left ventricular pressure. A proportionality of left ventricular and intramyocardial pressure is therefore not to be expected. The results on intramyocardial pressure obtained by the different methods used in the literature should be re-interpreted taking this concept into account. PMID- 2190554 TI - Substitution of proline with pipecolic acid at the scissile bond converts a peptide substrate of HIV proteinase into a selective inhibitor. AB - The nonapeptide H-Val-Ser-Gln-Asn-Tyr-Pro-Ile-Val-Gln-NH2 containing the retroviral Tyr-Pro cleavage site is a good substrate for the proteinase of human immunodeficiency viruses but it is not readily hydrolyzed by other nonviral proteinases including the structurally related pepsin-like aspartic proteinases. Replacing the Pro by L-pipecolic acid (2-piperidinecarboxylic acid) converted the substrate into an effective inhibitor of HIV-1 and HIV-2 proteinases with IC50 of approximately 1 microM. This compound showed a high degree of selectivity in that it did not inhibit cathepsin D and renin. PMID- 2190556 TI - Comparative study of the phenylalanyl-tRNA synthetases from Escherichia coli and Thermus thermophlus by the tritium topography method. AB - A comparative study of thermostability and aminoacid composition of the phenylalanyl-tRNA synthetases from E. coli and Thermus thermophilus HB8 has been carried out. Compared with the mesophilic enzyme, a considerable increase of Pro, Leu, Phe, Arg and decrease of Asx, Ile, Ser, Thr and Lys content have been revealed in the thermophilic protein. Using tritium topography, Pro, (Leu + Ile) and Gly were found to be the most accessible on the surfaces of both the enzymes. In the E. coli enzyme, Thr residues were also easy to access while on the surface of the thermophilic enzyme there were more Arg residues. The quantitative assay of the surface compositions revealed the increased exposure of the (Leu + Ile) residues on the thermophilic protein as well as of the charged Asx and Arg residues. A possible correlation of the observed effects with thermostability is discussed. PMID- 2190555 TI - Influence of DNA adenine methylase on the sensitivity of Escherichia coli to near ultraviolet radiation and hydrogen peroxide. AB - Near-ultraviolet (NUV) radiation and hydrogen peroxide (H2O2) inactivation studies were performed on Escherichia coli K-12 DNA adenine methylation (dam) mutants and on cells that carry plasmids which overexpress Dam methylase. Lack of methylation resulted in increased sensitivity to NUV and H2O2 (a photoproduct of NUV). In a dam mutant carrying a dam plasmid, the levels of Dam enzyme and resistance to NUV and H2O2 were restored. However, using a multicopy dam+ plasmid strain, increasing the methylase above wildtype levels resulted in an increase in sensitivity of the cells rather than resistance. PMID- 2190557 TI - Low-dose-rate effect of tritium beta-rays on transfection activity of phage DNA related to an oxidative species different from .OH, HO2. O2-., and H2O2. AB - In order to study the low-dose-rate effect of tritium beta-irradiation, we exposed single-stranded DNA of M13 mp10 phage to purified tritiated water. The beta-irradiated DNA was then transfected to E. coli K12 JM101. The lower the radiation dose rate, the more the transfection activity decreased. After the low dose-rate effect was confirmed, the characteristics of tritiated water were also studied. The formation of an active oxidative species different from .OH, HO2., O2-., and H2O2 was found in the tritiated water by using UV spectrometry and luminescence measurement. Attributing it to nescent oxygen by reason of the production of the epoxide from mesityl oxide, we discussed the low-dose-rate effect from the viewpoint that the yield of the DNA modification could be relatively higher than that of the O2 formation in a competition reaction when the dose rate was lower. PMID- 2190558 TI - Learning from our consumers. PMID- 2190559 TI - Salary determination of speech-language pathologists. Prediction and policy. PMID- 2190560 TI - Health Care Financing Administration Common Procedure Coding System. PMID- 2190561 TI - Guidelines for speech-language pathologists serving persons with language, socio communicative, and/or cognitive-communicative impairments. PMID- 2190562 TI - Standards for accreditation of educational programs. PMID- 2190563 TI - More on AuD. PMID- 2190564 TI - Enhanced DNA synthesis of cultured vascular smooth muscle cells from spontaneously hypertensive rats. Difference of response to growth factor, intracellular free calcium concentration and DNA synthesizing cell cycle. AB - It is widely reported that cultured vascular smooth muscle cells (CVSMCs) from spontaneously hypertensive rats (SHR) show enhanced proliferation compared with cells from Wistar-Kyoto rats (WKY). The present studies were designed to find out whether this exaggerated proliferation in SHR is determined genetically and, if so, to evaluate the mechanism on the cell cycle. (1) Incorporation of [3H]thymidine into DNA was enhanced in CVSMCs from 3- and 12-week-old SHR compared with WKY but not in CVSMCs from DOCA-salt hypertensive rats compared with the cells from sham-operated rats. (2) DNA synthesis in SHR cells was enhanced further by addition of insulin (which is considered to be a progression factor) but not by arginine-vasopressin (AVP; considered to be a competence factor) or by angiotensin II (AII). On the other hand, insulin, AVP and AII significantly augmented DNA synthesis in WKY cells. (3) Intracellular free calcium concentration was slightly, but significantly, higher in SHR cells. (4) An increase in the population of DNA-synthesizing S-phase cells and decrease in (G2 + M)-phase cells in SHR were observed by flowcytometry. These data suggest (1) that enhanced DNA synthesis in CVSMCs from SHR is determined genetically, (2) that enhanced DNA synthesis in CVSMCs from SHR is largely dependent on an increased proportion of S-phase cells and (3) that this increase in S-phase cells in CVSMCs from SHR could be due to enhanced competence gene expression in SHR cells. (4) The increased intracellular free calcium concentration is compatible with an activation of the inositol-trisphosphate pathway. PMID- 2190566 TI - Medical aspects of Arctic exploration 9. Down the Coppermine River to the Arctic Sea: Samuel Hearne (1769-1772). Part II. PMID- 2190565 TI - Double-blind multicenter trial on a new medium molecular weight glycosaminoglycan. Current therapeutic effects and perspectives for clinical use. AB - The ability of glycosaminoglycans to bind to a wide number of biologically active macromolecules has already been investigated. Recent clinical trials on the possible therapeutic benefits of glycosaminoglycans must be placed in perspective, even if they appear to be particularly encouraging, especially as regards the glycosaminoglycan effects on certain coagulation factors. A multicenter, medium-term, double-blind, crossover trial was performed by several Italian Lipid Clinics to determine whether administration of a medium molecular weight glycosaminoglycan (Sulodexide) has a significant clinical effect. Patients affected by peripheral vascular disease and/or hyperlipidemia (type IIa, IIb and IV) were submitted to a 4-week wash-out period, followed by parenteral Sulodexide (S) or placebo (P) administration for 2 weeks, another 2 week wash-out period, parenteral crossover drug or P administration for 2 weeks and, finally, oral S administration for 6 months. Sulodexide lowered plasma viscosity and plasma fibrinogen in all patients. There was also a drop in triglycerides together with a rise in apo A-I and HDL-C in type IV hyperlipoproteinemics, whereas there was no significant effect on total or LDL-plasma cholesterol in type IIa and IIb patients. Moreover, there was a percent increase in peak flow and rest flow in the lower limbs of peripheral vascular disease patients. No side effects or intolerance phenomena were detected. The results indicate that Sulodexide administration may be useful in long-term treatment of patients with peripheral vascular disease and a concomitant increase in plasma triglycerides and/or fibrinogen and/or viscosity. PMID- 2190567 TI - Architectural, morphometric and photometric features and their relationship to the main subjective diagnostic clues in the grading of prostatic cancer. AB - Novel software was developed to perform quantitative measurements of architectural and nuclear features in tissue sections. A pilot study was then undertaken to determine the diagnostic relevance of these quantitative features in prostatic tissue and the relationship of these objective features to the subjective clues used by practicing pathologists in the grading of prostatic adenocarcinoma. From a group of 82 cases of adenocarcinoma of the prostate with long-term follow-up, a subset of 15 cases that included 5 each in Mostofi grades I, II and III was carefully selected for analysis. Consecutive sections from each case were stained with hematoxylin and eosin or the Feulgen stain for visual and cytometric evaluations, respectively. The most important differences in the objective architectural features observed between the Mostofi grade I and II cases were the number of nuclei per gland and their distance from the glandular center. Significant differences were also noted in gland size and the variation in gland size. The Mostofi grades were also significantly different in terms of quantitative high-resolution features measuring nuclear size and its variation, total nuclear DNA content and the proportion of very aneuploid nuclei. There was a fairly good agreement between many of the subjective diagnostic clues and their corresponding quantitative architectural and nuclear features. This work (1) significantly extended the capabilities of our PC-based microphotometer system to analyze glandular tissue specimens, (2) provided insight into the objective bases for the expert diagnosis of adenocarcinomas of the prostate and (3) gave preliminary evidence of the ability of quantitative architectural features and high-resolution cytometric features to discriminate between the major diagnostic categories of these lesions. PMID- 2190568 TI - Computer-assisted grading of adenocarcinoma in prostatic aspirates. AB - Conventional cytologic grading of fine needle aspirates of prostatic adenocarcinoma has been shown neither to be reproducible nor to correlate well with histologic grading. This study developed a tumor grade classification based on computerized cytomorphometric features and compared the results to conventional grading of companion tissue sections. The image analysis system evaluated architectural features of the aspirates (mainly cell cluster features and interrelationships) as well as nuclear features. Thirty-five prostatic adenocarcinomas (8 well, 19 moderately and 8 poorly differentiated) were evaluated. Discriminant functions based on data collected at medium and high resolution distinguished between aspirates from low-grade (well-differentiated) and high-grade (poorly differentiated) adenocarcinomas with 81% accuracy. Moderately differentiated cancers could not be classified as a distinct group. This study suggests that accurate grading of prostatic adenocarcinoma in fine needle aspirate smears requires the evaluation of medium-resolution features related to specimen cellularity and uniformity or crowding of cell clusters as well as of high-resolution features of nuclear area, perimeter and coarseness of chromatin texture. These findings are compared to those of other schemes for the cytologic grading of prostatic aspirates. PMID- 2190569 TI - [The problems of microbial indication of water quality]. AB - In three experimental series the reliability of contemporary microbial indicators has been verified. It was shown that about 30% colonies growing on the Endomedium belongs not to family Enterobacteriaceae. The share of the so-called faecal coliforms growing at 44 degrees C is 54.6%. In comparison with the initial cultivations at the second passage this part increasing at about 126%. In waters of various quality is the viability of E. coli the smallest. Also on the Mc Conkey medium at 44 degrees C disappeared the colonies in order: E. coli (3-14 days), K. pneumoniae (3-21 days) C. freundii (21-28 days). This results brings an evidence that the existing indicator system for water quality should be revised. PMID- 2190570 TI - Construction of a bivalent oral vaccine for prevention of typhoid fever and cholera diarrhea. AB - A recombinant plasmid pMM-CTB containing the gene for production of the nontoxic B subunit of Vibrio cholera was transferred into a safe, effective and attenuated oral vaccine Ty21a strain of Salmonella typhi. The resulting Ty21a (pMM-CTB) could steadily produce CT-B subunit that was secreted extracellularly and had the same antigenicity as CT-B produced by V. cholera. Furthermore, the characteristics of the antigenicity, the persistance in mice and the galactose sensitivity possessed in the strain of Ty21a were also retained in Ty21a (pMM CTB). A bivalent vaccine containing Ty21a (pMM-CTB) and the killed whole cell of V. cholera was then constructed which had good immunogenecity for typhoid fever and cholera diarrhea. PMID- 2190571 TI - Lipogenesis stimulatory and inhibitory activities of the insulin mediators. AB - Incubating plasma membranes prepared from pig liver with varying concentrations of insulin (50-1000 microU/ml) resulted in the release of at least two insulin chemical mediators. One of them was fraction 1 of insulin mediator (M. W. 3700 4000 daltons) which had a significant lipogenesis-stimulating activity. The other was fraction 2 of insulin mediator (M. W. about 1000 daltons) which exhibited a lipogenesis-inhibitory activity. The ratio of yield between the two mediators produced from the membranes was not only dependent on the concentration but also on the potency of insulin and its analogs added. The result showed that there was more production of fraction 2 than fraction 1 with the inducer at low concentration (100 microU/ml), while the production of fraction 1 from the plasma membranes incubated with high concentration of insulin (300 microU/ml) was higher than fraction 2. On the other hand, insulin and its analogs which have different biological activities and receptor binding activities have been used to induce the insulin mediators. The results obtained were similar to those mentioned above. This suggested that the generation of the mediators was dependent on the biological potences but not the binding activities. PMID- 2190573 TI - [Storage of spermatozoa in the oviducts of birds: morphologic, histologic and functional approach]. AB - This paper reviews the studies devoted to the anatomical, histological and functional aspects of sperm storage in the oviduct of domestic birds (hen, turkey). Despite the presence of substances, such as lipids and mucopolysaccharides, in the cytoplasm of the cells encompassing the utero-vaginal glands (site of residence of spermatozoa in the oviduct after intra-vaginal inseminations), the absence of organelles involved in protein synthesis questions the existence of a secretory cycle in these glands. In the absence of such a cycle, the microvilli bordering the lumen of the utero-vaginal glands could participate in the purification of this micro-environment, thus allowing prolonged survival of spermatozoa in this region. Recent observations indicate that the mechanism controlling the penetration and/or storage of spermatozoa in the utero-vaginal glands is of an immuno-dependent nature and is closely related to the functional integrity of the glycocalyx surrounding the spermatozoon. A quantitative study of the kinetics of the storage of spermatozoa with or without alteration of their glycocalyx might help to explain its role (recognition of spermatozoa by the utero-vaginal glands or agglutination of spermatozoa within these glands). This type of experiment might also contribute to understanding the mechanism underlying the prolonged storage of spermatozoa in the utero-vaginal glands of birds. PMID- 2190572 TI - [Cholesterol and bile acid dynamics: comparative aspects]. AB - While the cholesterol concentration in a given tissue is similar in the rat, pig or man, the relative importance of the processes regulating the input (absorption and synthesis) and output (faecal cholesterol and bile acid excretions) of the cholesterol system is very different from one species to another. The rat, whose cholesterolaemia does not significantly increase after cholesterol addition to the diet ("hyporesponding" animal), successfully adapts its bile acid biosynthesis to variations in cholesterol input. This process accounts for 80 to 85% of cholesterol output, faecal cholesterol excretion being a minor process. The latter results from a low liver cholesterol secretion in the bile due to the low hydrophobicity of its main bile acids. Furthermore, in this animal a high intestinal synthesis of cholesterol and apolipoproteins (particularly B48) is observed. The latter are secreted as very light lipoproteins (chylomicrons and VLDL) with a faster plasma turnover than the VLDL (apoB100, E...) secreted by the liver. The "remnants" of rat VLDL are essentially very rapidly taken up by the liver; their interplasmatic transformation pathway into IDL and LDL is not very significant (less than or equal to 10%). Man, who has a more significant hypercholesterolaemia after exogenous cholesterol ingestion ("hyperresponding" subject) seems to have a less modulable capacity for transforming cholesterol into bile acids. This process accounts for only 50% of cholesterol output, faecal cholesterol excretion being quantitatively just as significant. Cholesterol concentration and the cholesterol/bile acid ratio are much higher in human than in rat bile, the main bile acids being more hydrophobic. While both the intestine and liver contribute to cholesterogenesis, the relative importance of the latter is probably greater in man than in the rat. Moreover, a larger fraction of plasma VLDL is transformed into IDL and LDL, the latter representing the main plasma cholesterol carrier. Determining whether the differences between the biodynamics of cholesterol processes in the rat and in man can be generalised to mammals with low or high sensitivities to hypercholesterolaemia and atherosclerosis seems to be a fundamental research objective for the next few years. PMID- 2190574 TI - [Spermatozoa transport in the oviduct of the chicken and the turkey]. AB - Recent studies of the storage and release of spermatozoa from utero-vaginal glands in birds have shown that: following intra-vaginal insemination, storage is completed within 2-3 d (domestic hen) or 1-5 d (turkey) and not within a few minutes or hours as previously described; as spermatozoa can be recovered from any segment of the oviduct during the egg formation cycle, it seems unlikely that sperm release from the utero-vaginal glands is directly dependent upon the egg formation cycle. The progressive inability of spermatozoa to agglutinate may be part of this mechanism. PMID- 2190575 TI - [Protein metabolism in the newborn lamb. IV. Consequences of amino acid and lactose ingestion]. AB - A study was made on protein metabolism and hormonal changes following birth in newborn lambs fed amino acids alone or in combination with lactose. Eight newborn lambs taken from their mother immediately after birth were fed hourly for 8 h, either with a solution of peptides and free amino acids obtained by mild hydrolysis of whey proteins (4 lambs; diet AP) or with the same solution + lactose (4 lambs; diet APL). L-[4,5-3H] leucine was continuously perfused into a jugular vein for 6 h when the lambs were 2 h 30 min old. Plasma glucose and insulin levels increased after birth in APL lambs whereas they decreased in the AP; these differences were significantly different. Plasma cortisol levels remained unchanged throughout the experiment. Free essential amino acid levels did not vary when lambs were older than 4.5 h; they depended on the corresponding amino acid intakes. Plasma free threonine, valine, isoleucine, leucine, tyrosine and lysine were lower in APL than in AP lambs. The plasma leucine irreversible loss and leucine oxidation were higher in AP than in APL lambs. The plasma flux of leucine from whole body protein breakdown was lower in APL than in AP lambs inasmuch as the plasma flux of dietary leucine may be estimated by the amounts of leucine ingested in both cases. No significant difference was found for the fractional synthesis rates of tissue proteins such as liver, skin, skeletal muscle, lung, brain and whole body. These rates for skin, muscle and whole body were close to those previously measured in colostrum fed lambs. The increase in whole body protein accretion resulting from lactose feeding in combination with amino acids seemed to result from a decreased protein breakdown that could be mediated by the insulin response. PMID- 2190576 TI - The hormonal control of ovine beta-lactoglobulin gene in cultured ewe mammary explants. AB - Mammary explants from pregnant ewes were cultured in the presence of insulin, cortisol and prolactin, either alone, or in combination. After 2 d of culture, total RNA was extracted from explants and the content of beta-lactoglobulin mRNA was estimated using a specific labelled cDNA probe. The mRNA for beta lactoglobulin was only deinduced slowly in the absence of hormone during the culture. Prolactin alone induced the accumulation of the mRNA. Insulin and cortisol added together were also stimulatory, but they only moderately amplified the prolactin effect. Beta-lactoglobulin gene in ewes, is therefore, controlled by the lactogenic hormones which also induce casein gene expression. The amplitude of the stimulation was unexpectedly low. This seems due in part to the fact that the gene was only deinduced weakly. In this respect, beta-lactoglobulin gene appears to be less dependent on lactogenic hormones under these experimental conditions than casein genes. PMID- 2190577 TI - Effect of intraluminal antibiotics on translocation of Candida albicans in burned guinea-pigs. AB - Guinea-pigs were pretreated orally with various antibiotics and given 3 x 10(10) Candida albicans by gastric lavage followed by a 40 per cent TBSA full skin thickness burn. The mesenteric lymph nodes, liver and spleen were cultured for the presence of viable organisms. Caecal contents were quantitatively cultured for aerobic bacteria and C. albicans. Clindamycin and penicillin G were the greatest promoters of translocation followed by the combination streptomycin/bacitracin. The mechanism for antibiotic-induced translocation is multifactorial centering on intestinal flora, anaerobic spectrum of the antibiotic and host defense as well as microbe virulence. The systemic use of broad-spectrum antibiotics, particularly those with strong anaerobic activity, should not be taken too lightly. A severely immunocompromised patient on this type of therapy may be prone to a severe fungal infection. This study reaffirms the concept that translocation from the gastrointestinal barrier is a potential source of life-threatening nosocomial infection. PMID- 2190578 TI - Imaging the carpal tunnel. PMID- 2190579 TI - The use of ultrasound in the management of primary psoas abscess. AB - Whereas psoas abscess secondary to many local intra- and extra-peritoneal septic processes is well recognised, primary psoas abscess is much less common and the diagnosis is often delayed, leading to significant morbidity and mortality. A case of primary psoas abscess is described and the role of ultrasound in the investigation and management is discussed. PMID- 2190580 TI - 1939-1989: Fifty years progress in allergy. A tribute to Paul Kallos. PMID- 2190581 TI - In memoriam Paul Kallos (1902-1988). PMID- 2190582 TI - Antitumoral and other biomedical activities of synthetic ether lysophospholipids. PMID- 2190584 TI - Glucocorticoids. PMID- 2190583 TI - The first set of antigens confronted by the emerging immune system. PMID- 2190585 TI - Origin and function of Mhc polymorphism. PMID- 2190586 TI - The thymus and its role in immunity. PMID- 2190587 TI - The T cell receptors. PMID- 2190588 TI - Paul Kallos (1902-1988): an almost complete bibliography. PMID- 2190589 TI - Lymphokines, monokines, cytokines. PMID- 2190590 TI - From Prausnitz-Kustner to passive cutaneous anaphylaxis and beyond. PMID- 2190591 TI - High-level expression of Escherichia coli tRNA (m5U54)-methyltransferase. AB - A cloning and high-expression system for tRNA (m5U54)-methyltransferase (RUMT) is described. Polymerase chain reaction (PCR) was used to replicate the coding sequence and create flanking restriction sites for cloning. The PCR product was then inserted into expression vectors containing the tac and PL promoters. With the PL promoter, induced cells produced about 1.5% of their soluble protein as catalytically active RUMT. With the tac promoter, up to 8% of the total cell protein was active enzyme, and RUMT was purified to near homogeneity in three steps. PMID- 2190592 TI - Rapid colorimetric detection of in vitro amplified DNA sequences. AB - A colorimetric assay to detect immobilized amplified nucleic acids has been designed. This approach provides a rapid assay, suitable for clinical diagnosis, to analyze DNA sequences amplified by the polymerase chain reaction. The specific DNA sequences are captured on a solid support by the use of a recombinant fusion protein consisting of the Escherichia coli lac repressor and staphylococcal protein A. The biotin streptavidin system is used to detect the immobilized material. Positive samples can be analyzed by direct solid-phase sequencing. Here, we show that this nonradioactive concept can be used for analysis of Staphylococci and Streptococci and for specific detection of the protozoa Plasmodium falciparum in clinical samples. PMID- 2190593 TI - Immunotoxic side-effects of drug therapy. AB - Adverse reactions to drugs in which an immune mechanism is responsible for toxicity have been described as idiosyncratic. Understanding these toxic effects is important to enable the identification of patients at risk. The specific toxic side effects considered are heparin-induced thrombocytopenia, penicillin-induced haemolytic anaemia, hepatitis as a result of halothane and tienilic acid therapy, quinine- and quinidine-dependent thrombocytopenia, methyldopa-induced haemolytic anaemia and immune-complex disease following administration of hydralazine, procainamide and penicillamine. The molecular mechanisms of immunotoxicity are presented where such information is available although more than one effect may contribute to the observed pattern of toxicity. The initial events leading to antibody production in certain individuals in response to drug therapy are not understood and, in many of the examples described, antibody production occurs in some patients who do not subsequently experience clinical problems. Clinically serious adverse effects involving immune reactions are infrequent, and a range of genetic and environmental circumstances need to be present simultaneously in an individual before toxicity develops. The ability to metabolise a particular drug has been shown to be one major predisposing factor in toxicity; the immunocompetence of the patient is likely to be another. Both of these considerations are subject to genetic and environmental controls, including infection and disease. PMID- 2190594 TI - Adverse effects of spinal and epidural anaesthesia. AB - Spinal and epidural blockade are similar in many respects in the anaesthesia they produce, since they both cause major conduction blockade with local anaesthetic agents. Physiologically, the blockade involves the production of a sympathectomy with venous pooling and decreased venous return, causing decreased cardiac output and hypotension. Physiological complications include bradycardia, heart block and, rarely, cardiac arrest. Nonphysiological complications include high or total block from extensive spread of the local anaesthetic agent, and toxic reactions from inadvertent intravenous injection of local anaesthetic during epidural administration. Neurological complications include paraplegia from either haematoma or abscess, arachnoiditis or trauma. Post-dural puncture headache is a persistent problem that is more pronounced in younger patients. Cranial nerve lesions are rarely seen with spinal anaesthesia. This review covers the adverse effects of spinal and epidural blockade and what can be done to prevent and/or treat them. With attention to proper performance and patient selection, spinal and epidural anaesthesia are safe and efficacious options when choosing anaesthetic technique. PMID- 2190595 TI - Monoamine oxidase inhibitor update. Potential adverse food and drug interactions. AB - Monoamine oxidase inhibitors (MAOIs) are medicines with potential for therapeutic gains, but they may also have adverse consequences. The risk: benefit ratio is assessed and, in appropriately selected cases, efficacy should outweigh disadvantages. Hypotension is the most prominent side-effect; yet the primary concern in the MAOI-treated person is to prevent co-exposure to substances with indirectly-acting sympathomimetic properties. Such co-utilisations from certain foods or drugs can result in dangerous hypertensive and hyperpyretic crises. A responsible individual should be involved in the administration of these drugs. The patient and family must fully understand the self-discretionary diet avoidance rules, which stress abstinence from high-tyramine foods. Drug prohibitions also emphasise elimination of indirect action sympathomimetics, but all pharmaceutical applications are always strictly controlled by the well informed physician who prescribes MAOIs. Treatment of the hypertensive crisis is urgent and includes alpha-blockade. Overdoses require supportive therapies and may necessitate acidification of the urine. PMID- 2190596 TI - Intra-articular steroid injection. A risk-benefit assessment. AB - Intra-articular injections with steroids may offer additional help in the treatment of inflammatory joint diseases. The major side effects are the systemic effects of steroids, infectious arthritis and cartilage damage. These are infrequent, however, and to a great extent preventable. Steroids are of little effect in radiological progression and function, and this is the most important limitation on liberal use. On the other hand, they powerfully suppress inflammation and pain, for a varying length of time which depends on the preparation used. PMID- 2190597 TI - Pentamidine. A risk-benefit analysis. AB - With the advent of the acquired immunodeficiency syndrome (AIDS), the therapeutic importance of pentamidine isethionate has greatly increased. This review summarises its pharmacology, its toxicity and clinical experience in the treatment of Pneumocystis carinii pneumonia (PCP). Data are conflicting as to whether pentamidine is more or less effective than cotrimoxazole (trimethoprim sulfamethoxazole) for the treatment of PCP in individuals with AIDS, but due to its toxicity and expense, it is considered as second-line therapy by many authorities. Hypoglycaemia has been encountered in up to 27% of treatment courses with pentamidine, and nephrotoxicity in 25%. In an attempt to circumvent the toxicities associated with parenteral administration, aerosolised delivery has been evaluated for both therapy and prevention of PCP. Aerosolised pentamidine, on the basis of early clinical results, convenience and low toxicity, may become the drug of choice for prevention of PCP in individuals at high risk. However, its role in the treatment of PCP remains to be defined. Preliminary studies suggest that it is effective, but the data are insufficient to support its use outside of clinical trials. PMID- 2190599 TI - Bibliography of the current world literature. PMID- 2190598 TI - Acid and alkaline diuresis. When are they of value in the treatment of poisoning? AB - The utility of both acid and alkaline diuresis has been brought into question because of the ability to increase the elimination rate of many toxins by less care-intensive methods such as repeated-dose charcoal. Alkaline diuresis is a technique which uses a common drug, but acid diuresis is not a technique known to most physicians. The former is currently the best therapy for quinine poisoning. Phencyclidine elimination is increased by 10%, but most patients recover with only supportive care. Acidification has been effective in some hands; data suggest that renal elimination is not the only mechanism of action of this therapy. In deeply comatose patients with hypotension, acidification should be considered. Alkalinisation, the mainstay of therapy for salicylate and phenobarbital poisoning over many decades, is effective, although no more so than charcoal, and less than dialysis. PMID- 2190601 TI - Bibliography of the current world literature. PMID- 2190600 TI - Evaluation of a microbiological method for zidovudine blood level determination. PMID- 2190602 TI - The American, British and Dutch responses to unlinked anonymous HIV seroprevalence studies: an international comparison. PMID- 2190603 TI - Replicative capacity of HIV-2, like HIV-1, correlates with severity of immunodeficiency. AB - We have obtained 15 HIV-2 isolates from the peripheral blood mononuclear cells (PBMCs) of 24 HIV-2-infected west African people. The frequency of virus isolation correlated with the severity of HIV-2 infection; only three isolates were obtained from 11 asymptomatic individuals, whereas virus was isolated from nearly all (12 of 13) individuals with symptoms. The HIV-2 isolates showed distinct replicative and cytopathic characteristics and, similarly to HIV-1 isolates, could be divided into two major groups: rapid/high and slow/low. Rapid/high isolates, i.e. isolates with the ability to replicate in tumour cell lines, were obtained from individuals with symptomatic HIV-2 infection and CD4+ lymphocyte counts less than 360/microliters blood; these isolates induced syncytia in PBMC cultures. HIV-2 isolates unable to replicate continuously in tumour cell lines (slow/low isolates) induced small syncytia, cell death, or no cytopathic effect at all. All HIV-2 isolates obtained from asymptomatic individuals showed a slow/low replication pattern. PMID- 2190604 TI - Simple methods for monitoring HIV-1 and HIV-2 gp120 binding to soluble CD4 by enzyme-linked immunosorbent assay: HIV-2 has a 25-fold lower affinity than HIV-1 for soluble CD4. AB - Sensitive enzyme-linked immunosorbent assay-based methods are described for monitoring the binding of envelope glycoproteins from HIV-1 and HIV-2 to soluble CD4 (sCD4). Each of the assays has different properties suitable for different applications, but all can be used to characterize recombinant antigens and to screen for inhibitors of the gp120-CD4 interaction. Recombinant mammalian gp120 (Celltech) binds to sCD4 with high affinity (3 nM); this interaction is inhibited by sera from HIV-infected individuals and by specific monoclonal and polyclonal antibodies raised to a component of the CD4 binding site on gp120. The affinity for sCD4 of HIV-2 viral gp120 is shown to be approximately 25-fold lower than that of HIV-1 gp120 (viral or recombinant). PMID- 2190605 TI - Characterization of recombinant gp120 and gp160 from HIV-1: binding to monoclonal antibodies and soluble CD4. AB - We compared four preparations of recombinant HIV-1 envelope glycoprotein: mammalian (Chinese hamster ovary cells) gp120 (Celltech); baculovirus gp120 from American Biotechnologies Inc. (ABT) and from MicroGeneSys (MGS); and baculovirus gp160 (Institute of Virology, Oxford, UK). Each envelope glycoprotein binds to a neutralizing monoclonal antibody (MAb) directed against the V3 loop, confirming the integrity of this type-specific neutralization epitope. MGS gp120 binds abnormally well to a MAb which recognizes an epitope preferentially exposed on denatured gp120. Consistent with this finding, MGS gp120 binds to soluble CD4 (sCD4) with an affinity 50-100-fold lower than that of Celltech gp120. The affinity of Celltech gp120 from sCD4 is 2.3 nM, indistinguishable from that of gp120 extracted from HIV-1 virions. Baculovirus gp120 (ABT) and gp160 also have a high affinity for sCD4. A significant proportion of anti-gp120 antibodies in HIV positive human sera recognize epitopes that are dependent on the mammalian glycosylation pattern, and a human HIV-positive serum inhibits the binding of mammalian gp120 to sCD4 five- to 10-fold more potently than it inhibits baculovirus gp120 binding to sCD4. PMID- 2190606 TI - Evaluation of a rapid membrane-based assay (HIV-CHEK) for detection of antibodies to HIV in serum samples from Nairobi. AB - We evaluated a rapid membrane-based assay (HIV-CHEK) for detection of antibodies to HIV using 737 serum samples in Nairobi, Kenya. The rapid assay had a sensitivity of 96.3% and specificity of 99.8% when compared with enzyme-linked immunosorbent assay (ELISA) and Western blot assay. Results were similar using fresh or previously frozen serum samples, although the latter occasionally left debris on the assay device membrane yielding uninterpretable results. This rapid HIV assay may be of particular use in developing countries where laboratory resources are limited. PMID- 2190607 TI - Sensitivity of six commercial enzyme immunoassay kits that detect both anti-HIV-1 and anti-HIV-2. AB - The sensitivities of six commercial combined anti-HIV-1/anti-HIV-2 enzyme immunoassays (EIAs) were evaluated, one assay (ELAVIA) based on whole virion antigen, two assays (Abbott, Wellcozyme) based on antigens expressed from recombinant DNA, and three assays (Biochrom, IAF Biochem and Pharmacia) based on synthetic peptides as antigens. All the kits investigated performed well on a panel of 47 routine anti-HIV-1-positive specimens, but on series of anti-HIV-1 seroconversion specimens from seven plasmapheresis donors, two of the peptide assays, Biochrom and Pharmacia, performed less well than the other assays. On a panel of anti-HIV-2-positive specimens, all the assays except Biochrom detected all 33 positive sera, though the reactions of some of them in the Abbott assay were relatively weak. In deciding whether to introduce a combined assay in place of an anti-HIV-1 assay, cost, specificity, the availability of confirmatory tests and the prevalence of HIV-2 in the locality, as well as sensitivity, should be considered. PMID- 2190609 TI - Effect of genetic background on cosegregation of renin alleles and blood pressure in Dahl rats. AB - The cosegregation of renin alleles and blood pressure was evaluated in segregating populations derived from inbred Dahl salt hypertension sensitive (S) and inbred Dahl salt hypertension resistant (R) rats. The populations were raised on high salt diet (8% NaCl). In F2 and F1 X S populations, there was a significant positive gene-dosage relationship between the S-rat renin allele and blood pressure. In contrast, no such relationship was seen in the F1 X R population. Since in the F1 X R population the genetic background is strongly influenced by genes from the R rat (75% R, 25% S), the result is interpreted to mean that genes at other (unidentified) loci modify the blood pressure effect of the S-rat renin allele. PMID- 2190608 TI - Hypertension and peripheral insulin resistance. Possible mediating role of intracellular free magnesium. AB - To investigate the association of hypertension and insulin resistance, we utilized 31P-NMR spectroscopy to noninvasively assess intracellular free magnesium levels (Mgif) in erythrocytes of normotensive (n = 20) and essential hypertensive (n = 20) subjects given an oral 100 g glucose load. In hypertensive compared with normotensive subjects, fasting glucose and insulin levels were similar, but the integrated insulinemic responses to glucose were 45% greater (312 +/- 13.4 v 215 +/- 7.5 microU/mL, P less than .001). In hypertension, Mgif levels were significantly reduced (183 +/- 9 v 251 +/- 9 mumol/L, P less than .001), and for all subjects were closely and inversely related to systolic (r = 0.77, P less than .001) and diastolic (r = -0.81, P less than .001) blood pressures, and to the integrated insulin response (r = -0.72, P less than .001). Furthermore, while insulin responses were also related to the underlying systolic (r = 0.69, P less than .001) and diastolic (r = .73, P less than .001) pressures, these relations were no longer significant when adjusted for Mgif levels. We hypothesize that hypertension and peripheral insulin resistance may be different clinical expressions of a common abnormal intracellular ionic environment, characterized at least in part by suppressed levels of intracellular free magnesium. PMID- 2190610 TI - Correspondences between the activity of the renin-angiotensin system and the erythrocyte Na+ transport abnormalities in hypertension. AB - Plasma renin activity and the relationship of renin activity and sodium excretion were analyzed in 50 untreated essential hypertensives classified according to their erythrocyte Na+ transport abnormalities. Renin activity was inappropriately high in 7 patients with increased activity of Na+,Li+ countertransport, inappropriately low in 12 patients with decreased activity of Na+,K+,Cl- cotransport and normal in 31 patients without either Na+ transport abnormalities. These results suggest that there are correspondences between the activity of the renin-angiotensin system and the main Na+ transport abnormalities present in erythrocytes of patients with essential hypertension. PMID- 2190612 TI - The potential benefits of nonpharmacological therapy. PMID- 2190611 TI - Clinical implications of hypertension in the diabetic patient. AB - We note that diabetes mellitus and hypertension coexist at a greater rate than would be indicated by chance. The combination of these two chronic disorders increases the risk of and mortality from such conditions as peripheral vascular disease, stroke, and nephropathy. Despite the importance of high blood pressure in diabetes, the underlying physiological mechanisms in this combined condition are poorly understood. This review explores the epidemiology, cardiovascular risks, pathophysiology and evaluation of this condition as well as outlining a general approach to treatment in the hypertensive diabetic. PMID- 2190613 TI - Issue dedicated to Dr. Morris Kates in honour of his valuable contributions to biochemistry in Canada. PMID- 2190614 TI - Lipid polymorphism and hydrocarbon order. AB - The use of 2H nuclear magnetic resonance for the characterization of the polymorphic behavior of lipids is illustrated. Different lipid phase preferences may be expected to influence the orientational order and its variation along the acyl chains. Several results are presented to support that view. An increase of motional freedom and a redistribution of the order along the acyl chains are observed during the lamellar-to-hexagonal phase transition, showing that the order profile is sensitive to the lipid phase symmetry. In addition, if the preferences for nonlamellar phases are not expressed explicitly, the presence of "nonbilayer" lipids constrained in bilayer environment induces increased hydrocarbon order. This suggests that order parameters of the acyl chains and lipid polymorphic tendencies are intimately related. PMID- 2190615 TI - Cloning and characterization of the N-acetylglucosamine operon of Escherichia coli. AB - Three enzymes are required for N-acetylglucosamine (NAG) utilization in Escherichia coli: enzyme IInag (gene nagE), N-acetylglucosamine-6-phosphate deacetylase (gene nagA), and glucosamine-6-phosphate isomerase (gene nagB). The three genes are located near 16 min on the E. coli chromosome. A strain of E. coli, KPN9, incapable of utilizing N-acetylglucosamine, was used to screen a genomic library of E. coli for a complementing recombinant colicin E1 plasmid that allowed for growth on N-acetylglucosamine. Plasmid pLC5-21 was found to contain all three known nag genes on a 5.7-kilobase (5.7-kb) fragment of DNA. The products of these nag genes were identified by complementation of E. coli strains with mutations in nagA, nagB, and nagE. The gene products from the 5.7-kb fragment were identified by [35S]methionine-labelled maxicells and autoradiography of sodium dodecyl sulphate-polyacrylamide electrophoresis gels. The gene products had the following relative masses (Mrs: nagE, 62,000; nagA, 45,000; nagB, 29,000. In addition, another product of Mr 44,000 was detected. The genes have been sequenced to reveal an additional open reading frame (nagC), a putative catabolite activator protein binding site that may control nagB and nagE, putative rho-independent terminator sites for nagB and nagE, and sequence homologies for RNA polymerase binding sites preceding each of the open reading frames, except for nagA. The calculated molecular weight (MWs) of the gene products derived from the sequence are as follows: nagA, 40,954; nagB, 29,657; nagC, 44,664; nagE, 68,356. No role is known for nagC, although a number of regulatory roles appear to be plausible. No obvious transcriptional termination site distal to nagC was found and another open reading frame begins after nagC. This gene, nagD, was isolated separately from pLC5-21, and the sequence revealed a protein with a calculated MW of 27,181. The nagD gene is followed by repetitive extragenic palindromic sequences. The nag genes appear to be organized in an operon: nagD nagC nagA nagB nagE. PMID- 2190616 TI - Relationship of phospholipid hexagonal phases to biological phenomena. AB - Phospholipid bilayers can undergo morphological rearrangements to other phases. The formation of one of these nonbilayer phases, the hexagonal phase, is preceded by an increase in the hydrophobicity of the bilayer surface and a destabilization of the bilayer structure. Certain membrane additives promote, while others inhibit, the formation of the hexagonal phase. Many of the molecular features that determine this phase preference are understood. Some of the properties of membranes are modulated by agents that affect the relative stability of the bilayer and hexagonal phases. Addition of bilayer stabilizers to a membrane decreases its fusogenic behaviour. One such bilayer stabilizer is cholesterol sulfate, which may function physiologically to inhibit the fusion of sperm cells. Several antiviral agents are also found to be bilayer stabilizers and some have been shown to inhibit membrane fusion phenomena. Another biological property that is modulated in a predictable manner by agents which affect the bilayer-hexagonal phase equilibrium is insulin-promoted glucose uptake in adipocytes. Bilayer stabilizers inhibit this process showing that the effects of insulin can be modulated by the bulk biophysical properties of the membrane. The activity of a number of membrane-bound enzymes is also lowered by bilayer stabilizers. Neutral and zwitterionic bilayer stabilizers are inhibitors of protein kinase C. Thus, the alteration of the bilayer-hexagonal phase transition by drugs may provide a useful parameter for predicting their effects on biological membranes. PMID- 2190617 TI - Purification of cloned proaerolysin released by a low protease mutant of Aeromonas salmonicida. AB - The precursor to the hole-forming toxin aerolysin has been purified in high yield from culture supernatants of a mutant of Aeromonas salmonicida containing the cloned structural gene. The mutant strain was generated by Tn5 mutagenesis. It released little or no protease or other extracellular proteins, including phospholipase, suggesting that it is a regulatory mutant. The absence of protease allowed the isolation of protoxin free from contaminating aerolysin. Typically, more than 50 mg of pure proaerolysin was obtained from 2 L of culture supernatant. The purified protein was completely unable to lyse human erythrocytes without prior activation with trypsin. PMID- 2190618 TI - The influence of K(+)-induced membrane depolarization on insulin secretion in islets of lean and obese (ob/ob) mice. AB - The present study was undertaken to determine whether factors that affect K+ permeability produce differences in insulin secretion in the islets of obese versus lean mice. At basal glucose (3 mM), the obese islets secreted more insulin for a given increment in depolarizing K+ concentration and responded to a wider range of K+ concentrations (5-45 mM) than the lean islets (5-25 mM). In contrast, the membrane potential changes induced by increments in pK+ were not significantly different in the two types of islets. The islets of lean and obese mice treated with pertussis toxin showed a qualitatively similar response to glucose and to epinephrine, but only the control and pertussis toxin treated obese islets responded to K+ depolarization when deprived of calcium. Abnormal responses to quinine and apamin were identified in the islets of obese mice. These findings show that the abnormal insulin secretory response of the obese islet is due, at least in part, to a defect independent of glucose metabolism. This is best explained by an altered sensitivity of voltage-dependent events, most likely the result of differential effects of an intracellular element acting on ATP-sensitive and Ca2(+)-activated K+ channels, both of which are implicated in membrane repolarization. PMID- 2190619 TI - Structure and dynamics of detergent-solubilized M13 coat protein (an integral membrane protein) determined by 13C and 15N nuclear magnetic resonance spectroscopy. AB - The major coat protein of the filamentous bacteriophage M13 is inserted as an integral protein in the inner membrane of the Escherichia coli host upon infection. M13 coat protein is an ideal model membrane protein and has been the target of many biophysical studies. An overview is presented here of the application of nuclear magnetic resonance spectroscopy to the study of the structure and dynamics of M13 coat protein in several lipid-mimetic environments. The coat protein may be biosynthetically enriched with 13C- and 15N-labelled amino acids, allowing the resolution and assignment of individual nuclei. Structural fluctuations at selected sites have been monitored using 13C relaxation and isotope-detected amide hydrogen exchange kinetics. A model is proposed for the structure of a coat protein dimer in detergent micelles. PMID- 2190620 TI - Antibodies to liposomal phosphatidylcholine and phosphatidylsulfocholine. AB - Antibodies against dimyristoyl phosphatidylsulfocholine or dimyristoyl phosphatidylcholine were raised in rabbits after injection of liposomes containing phosphatidylsulfocholine or phosphatidylcholine, cholesterol, and lipid A. The antibody activities were assayed by complement-dependent immune damage to liposomes and by a solid-phase, enzyme-linked immunosorbent assay using purified dimyristoyl phosphatidylcholine or dimyristoyl phosphatidylsulfocholine as antigen. Each antiserum raised against phosphatidylsulfocholine reacted with liposomes containing phosphatidylcholine, and each antiserum raised against phosphatidylcholine reacted with liposomes containing phosphatidylsulfocholine. However, adsorption of dimyristoyl phosphatidylsulfocholine antiserum with liposomes containing dimyristoyl phosphatidylcholine removed all activity against dimyristoyl phosphatidylcholine, but did not eliminate antibody activity against dimyristoyl phosphatidylsulfocholine. These results indicate that the antiserum against phosphatidylsulfocholine contained mixed populations of antibodies. Polyclonal antisera that have been appropriately adsorbed can therefore be obtained with a high degree of specificity for phosphatidylsulfocholine and such antisera can distinguish between phosphatidylsulfocholine and phosphatidylcholine. PMID- 2190621 TI - Potentiometric and spectroscopic properties of the cytochrome o complex of Escherichia coli. AB - Cytochrome o purified from cell membranes of Escherichia coli shows two potentiometrically distinct species with midpoint oxidation-reduction potentials of +265 +/- 5 and +140 +/- 15 mV. The component with the higher potential reacted with carbon monoxide and so likely is the oxygen-reacting heme of the cytochrome o complex. It appears to be responsible for the absorption maximum at 564 nm in reduced minus oxidized difference spectra measured at 77 K. The midpoint potential of the other component was sensitive to oxidation by ferricyanide. This latter component had an absorption maximum at about 554 nm. The inhibitor 2 heptyl-4-hydroxyquinoline N-oxide inhibited reoxidation of reduced cytochrome o by oxygen and modified the spectroscopic behaviour of the 564 nm component. The ratio of the heights of the maxima in the alpha-band region of the absorption spectrum differed in cytochrome o prepared from cloned material from that found in cytochrome o from noncloned sources, in spite of the similar polypeptide compositions of the two preparations. PMID- 2190623 TI - Antibodies to liposomal phosphatidylserine and phosphatidic acid. AB - Polyclonal antisera to phosphatidylserine or phosphatidic acid were induced in rabbits by injecting liposomes containing phosphatidylserine or phosphatidic acid and lipid A. Adsorption of antisera with liposomes containing different phospholipids revealed that some degree of reactivity with one or more phospholipids other than the immunizing phospholipid was often observed. However, cross-reactivity with other phospholipids was not a universal phenomenon, and one antiserum to phosphatidylserine failed to cross-react (i.e., was not adsorbed) with liposomes containing other phospholipids. All of the antisera were inhibited by soluble phosphorylated haptens (e.g., phosphocholine but not choline), but one of the antisera to phosphatidylserine was inhibited both by phosphoserine and by serine alone. Liposomal membrane composition influenced the activity of antiserum to phosphatidylserine. Regardless of whether unsaturated (beef brain) or saturated (dimyristoyl) phosphatidylserine was used in the immunizing liposomes, the antisera reacted more vigorously with liposomes containing unsaturated than saturated phosphatidylserine. We conclude that liposomes containing lipid A can serve as vehicles for stimulating polyclonal antisera to phosphatidylserine and phosphatidic acid. Although cross-reactivity with certain other phospholipids can be observed, sera from selected animals apparently can exhibit a high degree of specific activity to the immunizing phospholipid antigen. PMID- 2190622 TI - Mitochondrial import: properties of precursor proteins. AB - Most mitochondrial proteins are synthesized in the cytoplasm as higher molecular weight precursors and must cross at least one membrane to reach their final destination. Amino-terminal extensions of the precursors, termed signal peptides, have been shown to contain the necessary targeting information. Although no consensus sequence has been determined for signal peptides, all peptides examined to date have been shown to have membrane surface-seeking properties. The evidence so far seems to be consistent with a model in which the precursor initially associates with the lipids of the outer membrane and uses this surface to enhance subsequent diffusion to the import apparatus, thus modulating the overall rate of import. Precursors must at least partially unfold during import, although the extent and mechanism of unfolding remain unclear. The major possible mechanisms of unfolding include spontaneous unfolding of the precursor after engaging the translocation apparatus, ATP-dependent unfolding by a cytosolic factor (possibly the 70-kilodalton heat-shock proteins), and unfolding on the lipid surface of the outer mitochondrial membrane. It is possible that different types of precursors may utilize one or all of these mechanisms, in accordance with their individual needs. PMID- 2190624 TI - Wegener's granulomatosis. Thoughts and observations of a pathologist. AB - The clinical entity now known as Wegener's granulomatosis was first reported in 1936. Since then the disease's histopathology has been clarified, although its etiology remains unknown. Treatment requires immuno-suppressant therapy and careful following of affected patients. The present report reviews the historical background for the discovering of Wegener's granulomatosis and current clinical considerations. PMID- 2190625 TI - Histological evaluation of cochlear blood flow using different fixation methods. AB - For an accurate histological evaluation of cochlear blood flow, it is essential to fix the cochlear vessels while maintaining their physiological state. In the present study, we administered 10% CO2 to guinea pigs and then used phase contrast microscopy to determine how two different methods of fixation influenced the cochlear vasculature. The first method of fixation employed perilymphatic perfusion in vivo, while the second one involved fixation after decapitation. Decapitation caused significant changes in the vessels of the stria vascularis, including constriction and sludging. In contrast, no sludging occurred in the perilymphatic perfusion method and erythrocyte morphology was preserved. However, dilatation of the strial blood vessels occurred after the inhalation of 10% CO2 even in the decapitation method. The results demonstrate that particular attention must be paid to the fixation method used, especially when evaluating the blood flow of the stria vascularis. PMID- 2190626 TI - Prenatal maturation, the timing of birth and how it may be regulated in domestic animals. PMID- 2190627 TI - Sewall Wright (1889-1988). AB - The genetic contributions of Sewall Wright is briefly reviewed with special reference to J.B.S. Haldane's work. These include his work in population genetics, statistics, and animal breeding. PMID- 2190628 TI - Trends and differentials in ovarian cancer: incidence, mortality and survival experience. AB - Ovarian cancer was reported to be increasing in the 1970s. A continuously increasing trend has been anticipated for quite some time and an observation of international trends and differentials in the mortality, morbidity and survival from ovarian cancer is provided. Recent data on mortality and morbidity were obtained from the WHO and IARC data banks. Globally, ovarian cancer had moderate or relatively low rates for both mortality (1.5-10 per 100,000) and incidence (4 15 per 100,000), using standardized (world) rates. The ranges were the narrowest among all major cancers. The observed pattern of long-term trends was classified into three types: 1) increase followed by a plateau, then a decrease, 2) steady increase, and 3) uncertain. The rate was seen to be fairly high in the first group and still low in the second while it fluctuated in the third. A decrease of the rates in younger age-groups has extended to upper age-groups in countries with the first type of trend. Germ-cell tumours appeared more frequently in younger ages and low-incidence areas, while the common "epithelial" cancers were more apparent in older age-groups and high-incidence areas. The geographical differences seem to be smaller for germ cell carcinomas than the common "epithelial" carcinomas which may be associated more with environmental risk factors. Five-year survival rates improved to a range of 25-41% in the latter half of the 1970s. PMID- 2190630 TI - Clinical and pharmacological study of a novel controlled release preparation of salbutamol. AB - This study compared the efficacy of 8 mg controlled release (CR) salbutamol tablets twice daily with standard 4 mg salbutamol tablets four times daily in patients with chronic obstructive airways disease. There was significant bronchodilation in both treatment groups as measured by standard spirometry (P less than 0.05). With the CR preparation there was significantly less wheeze (P less than 0.05) and significantly reduced requirement for rescue bronchodilator (P less than 0.05). Salbutamol levels measured hourly on the final day of each treatment period showed that the drug profile in the CR group was smoother, without the troughs and peaks seen with standard tablets. PMID- 2190629 TI - Influence of acetylator status on the haemodynamic effects and pharmacokinetics of cadralazine in healthy subjects. AB - 1. Cadralazine is a new antihypertensive agent which causes peripheral vasodilation, probably mediated by a hydrazinopyridazine metabolite. 2. The possible influence of acetylator status on the pharmacokinetics and haemodynamics of the drug was studied in six fast and six slow acetylators over a period of 24 h after administration of a single 10 mg oral dose. 3. There were no differences between the two groups in AUC and Cmax values of cadralazine and apparent metabolite, the latter defined as the sum of the free and conjugated hydrazinopyridazine. Peak plasma concentrations of these compounds were reached after 1 h. Thereafter, the concentration of the metabolite declined more slowly than that of cadralazine. 4. No effects on blood pressure were noted. Changes in heart rate and plasma renin were delayed by 3-5 h with respect to the time-course of drug and metabolite in plasma; maximum responses occurred at 4-6 h after drug administration. The extent of the increase in plasma renin activity was slightly greater in slow than in fast acetylators, but the difference was not significant statistically. PMID- 2190631 TI - Fluorescence characterization of the interaction of various transfer RNA species with elongation factor Tu.GTP: evidence for a new functional role for elongation factor Tu in protein biosynthesis. AB - The ubiquity of elongation factor Tu (EF-Tu)-dependent conformational changes in amino-acyl-tRNA (aa-tRNA) and the origin of the binding energy associated with aa tRNA.EF-Tu.GTP ternary complex formation have been examined spectroscopically. Fluorescein was attached covalently to the 4-thiouridine base at position 8 (s4U 8) in each of four elongator tRNAs (Ala, Met-m, Phe, and Val). Although the probes were chemically identical, their emission intensities in the free aa-tRNAs differed by nearly 3-fold, indicating that the dyes were in different environments and hence that the aa-tRNAs had different tertiary structures near s4U-8. Upon association with EF-Tu.GTP, the emission intensities increased by 244%, 57%, or 15% for three aa-tRNAs due to a change in tRNA conformation; the fourth aa-tRNA exhibited no fluorescence change upon binding to EF-Tu.GTP. Despite the great differences in the emission intensities of the free aa-tRNAs and in the magnitudes of their EF-Tu-dependent intensity increases, the emission intensity per aa-tRNA molecule was nearly the same (within 9% of the average) for the four aa-tRNAs when bound to EF-Tu-GTP. Thus, the binding of EF-Tu.GTP induced or selected a tRNA conformation near s4U-8 that was very similar, and possibly the same, for each aa-tRNA species. It therefore appears that EF-Tu functions, at least in part, by minimizing the conformational diversity in aa-tRNAs prior to their beginning the recognition and binding process at the single decoding site on the ribosome. Since an EF-Tu-dependent fluorescence change was also observed with fluorescein-labeled tRNA(Phe), the protein-dependent structural change is effected by direct interactions between EF-Tu and the tRNA and does not require the aminoacyl group. The Kd of the tRNA(Phe).EF-Tu.GTP ternary complex was determined, at equilibrium, to be 2.6 microM by the ability of the unacylated tRNA to compete with fluorescent Phe-tRNA for binding to the protein. Comparison of this Kd with that of the Phe-tRNA ternary complex showed that in this case the aminoacyl moiety contributed 4.3 kcal/mol toward ternary complex formation at 6 degrees C but that the bulk of the binding energy in the ternary complex was derived from direct protein-tRNA interactions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2190632 TI - Effects of an anti-alpha monoclonal antibody on interaction of Escherichia coli RNA polymerase with lac promoters. AB - The anti-alpha monoclonal antibody, mAb 126C6, has been used to investigate the role of the alpha subunit in transcription initiation. mAb 126C6 strongly inhibits cAMP-CRP-dependent abortive initiation with lac P+, partially inhibits abortive initiation with the lac L8UV5 promoter, and is without effect on the d(A T)n-directed synthesis of r(A-U)n. DNase I footprinting shows that the preformed mAb 126C6-RNA polymerase complex does not bind to cAMP-CRP-lac P+; RNA polymerase specific protection is largely lost after incubation of the preformed RPo with mAb 126C6. Kinetic analysis of open complex formation by mAb 126C6-RNA polymerase with lac L8UV5 showed that changes in both the binding and the rate of isomerization account for the observed inhibition, with the isomerization step affected to a greater extent. Binding of cAMP-CRP to lac L8UV5 is RNA polymerase dependent. DNase I footprints show that as a consequence of mAb 126C6 binding of the preformed cAMP-CRP-lac L8UV5-RNA polymerase RPo, CRP dissociates from its site on the promoter. RNA polymerase protection of the promoter upstream from -41 is also lost. DNase I footprinting of mAb 126C6-RNA polymerase complexed with cAMP-CRP-lac P+ or -lac L8UV5 suggests that interactions between CRP and RNA polymerase are affected by binding of the anti-alpha mAb 126C6 to RNA polymerase. Protection methylation studies demonstrate that the formation of the mAb 126C6 RNA polymerase-lac L8UV5 open complex occurs at a slower rate and that nonoptimal contacts are established between mAb 126C6-RNA polymerase-lac L8UV5 promoter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190633 TI - 1H NMR studies on bovine cyclophilin: preliminary structural characterization of its complex with cyclosporin A. AB - Cyclophilin (163 residues, Mr 17737), a peptidyl prolyl cis-trans isomerase, is a cytosolic protein that specifically binds the potent immunosuppressant cyclosporin A (CsA). The native form of the major bovine thymus isoform has been analyzed by 2D NMR methods, COSY, HOHAHA, and NOESY, in aqueous media. The 156 main-chain amides in CyP yield 126 observable NH/alpha CH couplings (81%, Gly pairs counted as 1). Following exhaustive D2O exchange, 44 amide resonances remain visible. Further analysis of the NH/NH, NH/alpha CH, and alpha CH/alpha CH regions of the COSY and NOESY data sets indicates that the residual amides in D2O form a coherent hydrophobic domain which yields 2D NMR features suggestive of a beta-sheet. Many (43/126) of the amide resonances have been classified according to amino acid type. In the aromatic region of the spectra, the assignment of the ring spin systems is nearly complete (12/15 Phe, 2/2 Tyr, 1/1 Trp, and 3/4 His). This has successfully lead to the complete assignment of all of their beta CH's, main-chain alpha CH resonances, and many of the backbone amide resonances (8/12 Phe, 2/2 Tyr, 1/1 Trp, and 2/3 His). In other regions of the spectrum, the side chain and main-chain resonances for 10/23 Gly, 9/9 Ala, 5/11 Thr, 5/9 Val, and 1/6 Leu have been completely assigned. The drug-free cyclophilin and CsA-bound cyclophilin form two discrete protein structures that are in slow exchange on the NMR time scale. Comparison of the fingerprint regions from the COSY spectra obtained from the two forms of the protein reveals a minimum of 16 cross-peaks which are clearly shifted upon complexation. In fact, on the basis of chemical shift changes observed in assigned side-chain and main-chain resonances, only a relatively few of the amino acid residues identified to date are perturbed by complex formation. These include 3 Phe (8, 12, and 14) and the Trp in the aromatic region and 2 Ala (7 and 8) in the Ala/Thr region. In the upfield-shifted methyl region, an assigned Leu and Val spin system and a spin system labeled X10 (an Ile or Leu) are affected by complex formation. In addition, a new aliphatic spin system, labeled X11, which shows a close spatial relationship to the perturbed Phe12, is observed in this region of the spectrum. In summary, the regions of the protein altered by complex formation can be divided into two categories: a hydrophobic and a H2O-accessible domain.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2190634 TI - Fluctuating asymmetry: an epigenetic measure of stress. AB - (1) Fluctuating asymmetry (FA) is a useful trait for monitoring stress in the laboratory and in natural environments. (2) Both genomic and environmental changes can increase FA which represents a deterioration in developmental homeostasis apparent in adult morphology. Genetic perturbations include intense directional selection and certain specific genes. Environmental perturbations include temperature extremes in particular, protein deprivation, audiogenic stress, and exposure to pollutants. (3) There is a negative association between FA and heterozygosity in a range of taxa especially fish, a result consistent with FA being a measure of fitness. (4) Scattered reports on non-experimental populations are consistent with experiments under controlled laboratory conditions. FA tends to increase as habitats become ecologically marginal; this includes exposure to environmental toxicants. (5) In our own species, FA of an increasing range of traits has been related to both environmental and genomic stress. (6) Domestication increases FA of the strength of homologous long bones of vertebrate species due to a relaxation of natural selection. (7) FA levels are paralleled by the incidence of skeletal abnormalities in stressful environments. (8) Increased FA is a reflection of poorer developmental homeostasis at the molecular, chromosomal and epigenetic levels. PMID- 2190635 TI - Sex ratios and conditions required for environmental sex determination in animals. PMID- 2190636 TI - Preclinical safety testing of plastic products intended for use in man. AB - Plastic material is used for medical devices including biomaterial for numerous applications in man. These applications range from disposable plastic syringes to hip prostheses. In order to assume safety and to comply with legal requirements, preclinical tests are necessary. The plastic material employed should in most cases be tested or evaluated at three levels: (1) toxicity tests with the various ingredients used to manufacture the basic plastic, (2) toxicity tests with the final plastic and (3) toxicity tests with the final device. However, individual testing protocols are required due to the different toxicological profiles of the plastics and the heterogenicity of their application-sites in man. This paper evaluates the studies which may be needed to fulfill these requirements. PMID- 2190637 TI - Biostatistical collaboration in medical research. AB - There has been an explosive growth in the development of statistical methodology over the past several decades. Research in both medicine and public health, in which the involvement of biostatisticians has increased dramatically during this period, has been both a beneficiary of this new methodology as well as a source of new problems. The contributions of statistical methodology in design, implementation, and analysis as they relate to the role that biostatistics and biostatisticians now play in the field of medical research are addressed. We comment on: (1) the acceptance by the medical community that biostatistical concepts are an integral part of sound medical research; (2) the sometimes unrealistic expectations placed on biostatistics and biostatisticians given limited resources and/or limited control; (3) some controversies among biostatisticians; and (4) the need for emphasizing the design and implementation phases of medical investigations. PMID- 2190638 TI - Some diagnostic methods for Cox regression models through hazard smoothing. AB - In this paper some graphical methods are proposed for evaluating the fit of Cox regression models in survival analysis. The simplest procedure proposed is to estimate the baseline hazard separately within subgroups by applying kernel-based smoothing to standard cumulative hazard estimates. The different estimates should be the same, to within sampling variability, when the model is correct. A modification of this procedure gives a direct way of calculating smooth estimates of hazard ratios over time. A further modification gives estimates of ratios as a function of a continuous covariate and time. The methods are applied to data taken from a clinical trial of adjuvant therapy for breast cancer. PMID- 2190639 TI - Recombinant human interleukin-3 expands the pool of circulating hematopoietic progenitor cells in primates--synergism with recombinant human granulocyte/macrophage colony-stimulating factor. AB - The in vivo effect of recombinant human interleukin-3 (rhIL-3) on peripheral blood (PB) levels of hematopoietic progenitor cells was studied in nonhuman primates. Subcutaneous administration of 33 micrograms/kg/d of rhIL-3 for 11 to 14 days to rhesus monkeys slightly raised leukocyte counts (twofold) and substantially expanded the pool of circulating stem cells in the second week of treatment. At the end of rhIL-3 administration, PB levels of granulocyte/macrophage colony-forming units (CFU-GM) increased by a mean of 12 fold; burst-forming units-erythroid (BFU-E) by ninefold; CFU-mix, by 12-fold; and CFU-megakaryocyte (Mk), by 13-fold as compared with their respective pretreatment values. Subsequent administration of recombinant human granulocyte/macrophage colony-stimulating factor (rhGM-CSF; 5.5 micrograms/kg/d for 5 days) to rhIL-3 pretreated animals further expanded the PB stem cell compartment leading to maximum levels of CFU-GM that were in average much more increased (63-fold) than CFU-GM levels under rhIL-3 (14-fold) or rhGM-CSF (12-fold) alone. This hitherto unknown effect of rhIL-3 on the pool of circulating progenitors, particularly in synergy with rhGM-CSF, may facilitate harvest of hematopoietic progenitor cells from PB for stem cell transplantation. PMID- 2190640 TI - Polarized fibronectin secretion and localized matrix assembly sites correlate with subendothelial matrix formation. AB - Endothelial cells in vivo form the interface between the vascular and interstitial compartments and are strategically located to mediate vascular permeability and hemostasis. One mechanism endothelial cells use to maintain a nonthrombogenic surface is to polarize basement membrane constituents to the basolateral cell surface. In the present study, we began characterization of the mechanisms used by endothelial cells in the assembly of a subcellular fibronectin matrix. Immunofluorescence microscopy was used to localize extracellular matrix fibronectin in endothelial cell cultures. In contrast to preconfluent and newly confluent cultures, post-confluent cultures assembled a fibronectin matrix that was restricted to the basolateral cell surface. To determine if endothelial cells polarize fibronectin secretion, Millicell culture inserts were used to distinguish proteins secreted from apical and basal surfaces. Preconfluent and newly confluent cultures secreted fibronectin equally into apical and basal media. In contrast, post-confluent endothelial cells secreted fibronectin preferentially into the basal chamber. The degree to which fibronectin secretion was polarized varied with time in culture and with the ability of the monolayers to act as a barrier to the movement of 125I-fibronectin from the apical to basal chamber. In addition, high affinity binding sites for exogenous 125I-fibronectin were found to be present on the basolateral, but not apical, surface of post confluent endothelial monolayers. These results indicate that subendothelial matrix assembly correlates with polarized fibronectin secretion, culture confluence, and expression of high affinity binding sites for fibronectin on the basolateral cell surface. PMID- 2190641 TI - Selection of U937 histiocytic lymphoma cells highly responsive to phorbol ester induced differentiation using monoclonal antibody to the eosinophil cytotoxicity enhancing factor. AB - Monoclonal antibodies (MoAbs) to the eosinophil cytotoxicity-enhancing factor (ECEF) were used to detect ECEF in U937 cells before and after phorbol ester (PMA)-induced differentiation into ECEF-secreting macrophages. Membrane associated ECEF (mECEF), apparently an integral membrane component, is found in U937 cells and in 70% of monocytes and, at lower levels, on blood T lymphocytes. Expression of mECEF in U937 cells is heterogeneous, as is responsiveness to PMA. In PMA-treated cultures, the strongest mECEF expression is on adherent, differentiated macrophages, rather than on activated, nonadherent cells. To study the relationship of mECEF to PMA responsiveness, we positively selected by "panning" a cell line (U937 P+) with significantly higher mECEF expression than that of U937. U937 P+ cells respond to PMA as a differentiation stimulus more effectively than do U937 cells, with a fourfold increase in the number of differentiated macrophages (P less than .001) and a faster rate of differentiation (a fourfold increase at t = 12 hours, P less than .001). U937 P+ cells also show a 7.4-fold increase in response to suboptimal doses of PMA (P less than .001). These findings suggest that mECEF expression correlates with responsiveness to a differentiation stimulus in a histiocytic lymphoma cell line that is widely used as a model of monocyte maturation. PMID- 2190642 TI - Hemolytic uremic syndrome associated with verocytotoxin-producing Escherichia coli infection in acquired immunodeficiency syndrome. PMID- 2190643 TI - Platelet activation may explain the storage lesion in platelet concentrates. AB - While the exact nature of the dysfunction of stored platelets is not known, it is generally agreed that the platelet's metabolic activity with lactate accumulation presents a significant impediment to prolonged storage. There is an increasing body of evidence that stored platelets have become activated in the preparation and handling of platelet concentrates. Changes in platelet function and structure in concentrates can be explained in terms of sequelae of activation, especially heightened metabolic activity and activation-specific changes in surface glycoproteins on stored platelets. With the use of inhibitors of platelet activation in the preparation of platelet concentrates, the loss of platelet function and integrity is less rapid and platelet metabolic rate is decreased during an extended storage period. Surface levels of glycoprotein Ib, normally decreased during prolonged storage of platelets, are well-preserved in the presence of activation inhibitors. When the use of inhibitors is combined with replacement of plasma with an artificial medium, platelets stored for up to 20 days appear to be metabolically and structurally intact and responsive to stimuli. In summary, platelet activation appears to play a major role in the generation of the storage lesion in platelet concentrates. PMID- 2190644 TI - Altered neutrophil functions in patients with large burns. AB - Neutrophil functions were examined longitudinally in 16 patients with large burns using multiparameter flow cytometry (FCM). At admission and through the first 10 days, the neutrophil expression of surface complement receptors for C3b (CR1) and C3bi (CR3) was increased, whereas neutrophil Fc receptor III (FcRIII) expression decreased. The phagocytosis of C3-opsonized Candida albicans increased during the same time period, whereas the ingestion of Ig-opsonized C. albicans decreased. The neutrophil intracellular killing of C. albicans was reduced by about 25% at admission. The microbicidal capacity was further compromised during the next 2 weeks, with a 50% reduction of intracellular killing 10 days following injury. The kinetics of neutrophil phagolysosomal acidification was altered during the first 20 days after burn injury, as the initial alkalinization of the phagolysosomes documented in control neutrophils could not be demonstrated in patients cells. In addition, patient neutrophil H2O2-production, which was only slightly reduced at admission, was gradually decreased during the first 2 weeks, with an oxidative burst about 40% lower than controls at day 10. All neutrophil functions tested were normal at discharge. The results demonstrate significant metabolic and functional alterations in neutrophils from patients with large burns. The data are consistent with a general activation of circulating neutrophils in the early phase after thermal injury, which is followed by impairment of neutrophil microbicidal mechanisms that may predispose for infectious complications. PMID- 2190645 TI - Human mononuclear phagocyte activation antigens. AB - Activation of mononuclear phagocytes causes changes in plasma membrane composition that include the expression of surface antigens and receptors. Monoclonal antibody technology has made it possible to identify and characterize newly expressed surface antigens. Among these "activation antigens" is a glycoprotein, Mo3, which (among hematopoietic cells) is selectively expressed by human mononuclear phagocytes that have been exposed to inflammatory factors in vitro and in vivo. Progress toward a functional and structural analysis of Mo3 is described. PMID- 2190646 TI - Blood cells and ischemia-reperfusion injury. AB - Ischemia-reperfusion insults are common clinical problems which involve most notably the heart (myocardial infarction) and brain (stroke). However, these and other organs are susceptible to damage following warming after cold injury, trauma, shock, and/or preparation for transplantation. Although the mechanisms responsible for reperfusion damage following ischemia and reperfusion are unknown, they are the focus of intense interest and investigation. This review briefly addresses our recent research related to the potential contributions of blood cells to the development of ischemia-reperfusion injury. PMID- 2190647 TI - Activation of neutrophils: measurement of actin conformational changes by flow cytometry. AB - Actin, which comprises approximately 10% of the weight of cytoplasmic protein of neutrophils, is the principal component of the cytoplasmic microfilament lattice. It can exist in either of two physical states, G-actin, which is monomeric, or F actin, which is polymeric or filamentous. Actin microfilaments support many forms of cell movement. Continuous remodeling of the microfilament lattice, which seems integral to sustained movement, is possible in part because of the ability of actin to change rapidly between its monomeric G-state and its filamentous F state. Changes in the G- and F-actin equilibrium may be studied by flow analysis using a fluorescent probe which is specific for F-actin, 7-nitrobenz-2-oxa-1,3 diazole-(NBD)-phallacidin. Alterations in neutrophil F-actin have been measured in response to chemotactic agents (e.g., formyl peptides and leukotriene B4), inhibitors of cell movement (e.g., N-ethylmaleimide and cytochalasin B), agents that promote the oxidative burst (e.g., formyl peptides and phorbol esters), and priming agents [e.g., tumor necrosis factor (TNF)]. Measurements may be taken at intervals of a few seconds, allowing comparison of rapid changes in the F-actin content to other rapidly occurring changes, such as altered membrane ion permeability and activation of cellular enzymes. The use of metabolic inhibitors has allowed dissection of some of the biochemical pathways involved in actin assembly in living cells. Although clinical studies are few thus far, the technique has also been used to study basal and stimulated F-actin levels in circulating neutrophils in neonates and in family members of patients with neutrophil-actin dysfunction. PMID- 2190648 TI - Proinflammatory and procoagulant effects of herpes simplex infection on human endothelium. AB - Atherosclerotic lesions have been reported to contain herpes simplex virus (HSV) genomic material. This and other evidence suggests that latent viral infection may be an atherogenic trigger. Moreover, active HSV lesions manifest histologically marked fibrin deposition in microvessels. Our laboratory tested in vitro whether HSV infection would cause human umbilical vein endothelial cells to become procoagulant and attract inflammatory cells. Early infection of human endothelial cells with HSV-1 alters the surface conformation as detected by merocyanine 540 staining. The efficiency of prothrombinase complex assembly increases, resulting in a two- to threefold accelerated rate of thrombin generation on the cell surface of virally infected endothelium. HSV infection of endothelium results in a marked increase in thrombin-induced platelet adhesion with a concomitant decrease in prostacyclin secretion in response to thrombin. Viral infection enhances coagulation by decreasing endothelial thrombomodulin expression and subsequent activation of protein C. Viral infection also induces tissue factor in human endothelial cells within 4 hours of infection. Not only does the endothelial monolayer become procoagulant when infected with HSV, it also becomes a more adherent surface for granulocytes. Resting and stimulated granulocyte adherence is enhanced twofold on virally infected endothelium. Enhanced adhesion is accompanied by excessive granulocyte-mediated lysis of 51Cr labeled HSV-infected endothelium and endothelial cell detachment from its substrate. Exaggerated endothelial detachment correlated with poor binding of infected endothelial cells to substratum matrix proteins. Resuspended virus infected cells bound significantly less well to tissue culture containers coated with fibronectin, laminin, and type IV collagen. HSV-infected endothelium alters the anticoagulant properties of the endothelium causing it to become procoagulant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190649 TI - The role of the neutrophil in inflammatory diseases of the lung. AB - Under certain circumstances, the neutrophil has been implicated in causing disease by damaging normal host tissue. This may occur in the adult respiratory distress syndrome (ARDS). The neutrophil has been implicated since a) substances that activate neutrophils are produced in association with the predisposing risks that lead to ARDS; b) activated neutrophils migrate into the alveolar spaces and their toxic products can be found in lung lavage fluid and in the breath of patients with ARDS; and c) the magnitude of the physiologic alterations correlate with the number of neutrophils in the alveolar space. Additionally, the neutrophils may be primed by substances which are released by activated platelets within the confines of the lung. Both platelet adenine nucleotides and the platelet-derived extracellular matrix protein (ECM), thrombospondin, can prime the neutrophil for subsequent O2- generation following activation of the cells with the chemotactic peptide, F-met-leu-phe (FMLP). Furthermore, neutrophils can be primed or O2- generation by the basement membrane ECM protein, laminin. Since neutrophils express receptors for both laminin and thrombospondin, these constituents may serve to modulate neutrophil behavior for subsequent oxidative metabolism and contribute to exacerbating pulmonary disease. PMID- 2190650 TI - Detection of platelet activation using activation specific monoclonal antibodies. AB - Platelets may become activated in a number of clinical disorders and participate in thrombus formation. Blood tests reflecting in vivo activation are therefore potentially useful in evaluating patients with thrombotic diseases. Three types of monoclonal antibodies have been described that react preferentially with activated platelets. Antibodies against a 53-kD lysosomal granule protein, and antibodies that recognize a 140-kD alpha-granule protein, are two types expressed on the platelet surface during secretion. A third type is not dependent on secretion and recognizes activation-dependent changes in the configuration or microenvironment of the platelet glycoprotein IIb/IIIa complex. Several procedures were used to detect platelet activation, using radiolabeled or fluorescent antibodies. In a number of disorders, changes in platelets, reflecting activation, could be detected. For the study of in vitro and in vivo platelet activation, these tests may be useful, but further studies are needed to confirm the power and efficiency of this approach compared to other routine tests. PMID- 2190651 TI - Current concepts for a drug-induced inhibition of formation and action of thromboxane A2. AB - Urinary and plasma metabolites of thromboxane A2 (TxA2) indicate an increased TxA2 synthesis in a number of diseases, whereby TxA2 is assumed to contribute to the underlying pathomechanisms by its profound effects on platelet aggregation and smooth muscle contraction. In some clinical situations the increment in TxA2 biosynthesis is accompanied by an increased formation of prostacyclin (PGI2) which is one of the most potent inhibitors of platelet activation and smooth muscle contraction. Therefore, drugs are being developed which suppress the formation or action of TxA2 without interfering with its functional antagonist PGI2. Low doses of acetylsalicyclic acid (ASA) preferentially inhibit cyclooxygenase activity in platelets and the synthesis of TxA2 in vivo. However, neither low doses (approximately 300 mg/day) nor very low doses spare the formation of PGI2 completely. Despite its limited selectivity, very low dose ASA (approximately 40 mg/day) provides an attractive perspective in TxA2 pharmacology. Although thromboxane synthase inhibitors selectively suppress TxA2 biosynthesis PGH2 can accumulate instead of TxA2 and substitute for TxA2 at their common TxA2/PGH2 receptors. Thromboxane synthase inhibitors can only exert platelet-inhibiting and vasodilating effects if PGH2 rapidly isomerizes to functional antagonists like PGI2 that can be formed from platelet-derived PGH2 by the vessel wall. TxA2/PGH2 receptor antagonists provide a specific and effective approach for inhibition of TxA2. These inhibitors do not interfere with the synthesis of PGI2 and other prostanoids but prevent TxA2 and PGH2 from activating platelets and inducing smooth muscle contractions. Most of the available TxA2/PGH2 receptor antagonists produce a competitive antagonism that can be overcome by high agonist concentrations. Since in certain disease states very high local TxA2 concentrations are to be antagonized, non-competitive receptor antagonists may be of particular interest. Some recent TxA2/PGH2 receptor antagonists produce such a non-competitive type of inhibition due to their low dissociation rate constant. As a consequence, agonists like TxA2 or PGH2 only reach a hemiequilibrium state at their receptors, previously occupied by those antagonists. A combination of a thromboxane synthase inhibitor with a TxA2/PGH2 receptor antagonist presents a very high inhibitory potential that utilizes the dual activities of the synthase inhibitor to increase PGI2 formation and of the receptor antagonist to antagonize PGH2 and TxA2. Such combinations or dual inhibitors, combining both moieties in one compound, prolong the skin bleeding time to a greater extent than thromboxane synthase inhibitors and even more than low dose ASA or TxA2/PGH2 receptor antagonists. PMID- 2190653 TI - Tuberculosis in developing countries: burden, intervention and cost. PMID- 2190654 TI - WHO/tuberculosis information systems. Computerized selective tuberculosis bibliography. PMID- 2190652 TI - Interleukin-4. A regulatory protein. AB - Since its discovery in 1982, numerous biological activities of interleukin-4 (IL 4) have been described. Like other cytokines, IL-4 is highly pleiotropic, both with respect to the number of different target cells that are responsive to it and with respect to the number of different biological responses it elicits. Interleukin-4 was initially described as a costimulant for the proliferation of B lymphocytes stimulated with anti-IgM antibody. Synonyms for this cytokine are B cell growth factor-1 (BCGF-1) and B cell stimulatory factor-1 (BSF-1). After cloning of both the murine and human IL-4, the use of recombinant IL-4 enabled detailed studies of its biological functions. Many cell types, mainly of hematological origin, express receptors for IL-4. Accordingly, effects of IL-4 have been described on B lymphocytes, T lymphocytes, NK cells, mononuclear phagocytes, mast cells, fibroblasts and hematopoietic progenitor cells. Currently, there are three major areas in which IL-4 appears to play an important role: 1) regulation of B cell growth and of antibody isotype expression. In this context, a possible role for IL-4 in allergic reactions is of special interest. 2) Stimulation of T cell growth and the generation of cytotoxic T lymphocytes. In addition to the suppressive effects on the induction of non HLA-restricted cellular cytotoxicity by natural killer- (NK) and lymphokine-activated killer (LAK) cells, this suggests a role for IL-4 in the regulation of cellular immune responses. 3) Regulation of the growth and differentiation of hematopoietic bone marrow stem cells. IL-4 itself does not induce proliferation of hematological progenitor cells but it can modulate the growth-factor dependent proliferation of these cells. In this review the biological functions of IL-4, reported until present, are discussed. PMID- 2190655 TI - Co-modulation masking release: spectro-temporal pattern analysis in hearing. AB - The peripheral auditory system is often modelled as containing an array of bandpass filters (called the auditory filters), each tuned to a different centre frequency. When a subject tries to detect a sinusoidal signal in noise, it has traditionally been assumed that performance is based on the output of the single auditory filter which gives the highest signal-to-masker ratio. However, recent experiments demonstrate the ability to compare the outputs of different auditory filters to enhance signal detection. This enhancement takes place especially when the envelope of the masker fluctuates over time, and when the fluctuations are coherent or correlated across different frequency bands. This phenomenon is called comodulation masking release (CMR) and it demonstrates the ability of the auditory system to perform a highly flexible spectro-temporal pattern analysis. CMR appears to be reduced or absent in persons with cochlear hearing loss, and this may partly account for the difficulties experienced by these persons in understanding speech in noisy backgrounds. PMID- 2190656 TI - Psychological characteristics of children with functional hearing loss. AB - The terminology used to describe functional hearing loss (FHL) and some explanations of the phenomenon are discussed briefly. Previous studies of FHL in children are reviewed. Characteristics of 30 children seen for psychological assessment following diagnosis of FHL are described. There were twice as many girls as boys in the sample. A large proportion of the children had experienced middle ear problems. The mean IQ for the sample was below average, but the range of intellectual ability was wide. Nine children showed serious educational retardation. The children were assigned to one of three psychological problem groups depending on whether they had minor, school-based, or deeper, psychological problems. Those with deeper psychological problems tended to show greater hearing losses on pure tone audiometry. FHL seemed to be related to attentional factors in those with only minor or school-based problems but not for those with deeper psychological problems. These findings are discussed with reference to the need for psychological assessment of children with FHL. PMID- 2190657 TI - Gene therapy using bone marrow transplantation: a 1990 update. AB - The use of recombinant retroviruses for gene transfer into the haematopoietic tissue in vivo is still a new area of research. The initial results of in vitro studies were very exciting. In contrast, the early in vivo studies in mice were somewhat disappointing because of the transient and low levels of expression of the transferred gene. Recently, however, better results have been obtained in the murine system in vivo. New packaging cell lines have been constructed, which are safer and still efficient. Better vectors have been designed. Thus, significant levels of expression of the transgene have been achieved in murine long-term transplant recipients. However, the results obtained so far in large animal studies are still disappointing. It should be emphasized that further progress must be based on a simple overall strategy involving better understanding of the functioning of the gene to be transferred by gene expression studies, design of vectors carrying a fully active and correctly regulated minilocus and better knowledge of the biological properties of the target cells, the haematopoietic stem cells. PMID- 2190658 TI - Bone marrow transplantation in comparison with conventional therapy in children with adult type chronic myelogenous leukemia. AB - From 1983 to 1988 14 patients under 16 years of age with adult type chronic myelogenous leukemia (CML) in chronic or blastic phase were treated by allogeneic bone marrow transplantation (BMT) in our center. These comprise 54% of all patients under 16 years of age grafted for this disease in FRG. These BMT patients were compared with 24 similar patients treated conventionally with busulfan and/or hydroxyurea in various centers. The probability of an event-free survival 5 1/2 years after BMT was 0.61 (SD 0.16); the estimated probability of survival for 3-8 years after diagnosis in the group treated by GMT was 0.78 (SD 0.14) vs 0.55 (SD 0.12) for the non-BMT group. The difference is not significant. In the BMT group only two patients died of transplant-related complications. The non-BMT patient with the longest survival period died recently 10 years after diagnosis. For children with adult type CML, BMT is a safe and effective treatment, and should be recommended if there is an HLA compatible sibling donor or even a fully compatible unrelated donor. However, for a more conclusive comparison between bone marrow transplantation and conventional treatment a longer observation period and larger patient numbers are necessary. PMID- 2190659 TI - A role of herpes virus serology for the development of acute graft-versus-host disease. Leukaemia Working Party of the European Group for Bone Marrow Transplantation. AB - Pretransplant herpes virus serology and acute graft-versus-host disease (GVHD) were studied in 379 leukaemic bone marrow transplant (BMT) recipients and their HLA-identical sibling donors. In logistic multivariate regression analysis pretransplant seropositivity to three or more different herpes viruses among the recipients was the only significant factor associated with grade II-IV acute GVHD (p = 0.03). If this factor was excluded, older donor age (p less than 0.001), absence of T cell depletion (p less than 0.001), pharmacological immunosuppression by monotherapy of methotrexate or cyclosporin versus a combination therapy of both (p = 0.002), and seropositivity to three or more herpes viruses among the donors (p = 0.03) prior to BMT, were also significantly associated with acute GVHD. The data indicate that latent herpes viruses in the host may act as minor histocompatibility antigens or by other means to trigger acute GVHD. PMID- 2190661 TI - Busulfan/cyclophosphamide plus bone marrow transplantation is not sufficient to eradicate the malignant clone in juvenile chronic myelogenous leukemia. AB - Bone marrow transplantation plays an essential role in the successful treatment of both juvenile and adult chronic myelogenous leukemia. Recently, it has been reported that conditioning with high doses of busulfan can successfully replace total body irradiation (TBI), in patients with acute myelogenous leukemia as well as adult chronic myelogenous leukemia. We report here the case of a 29-month-old boy with juvenile chronic myelogenous leukemia (JCML) transplanted with HLA identical bone marrow after conditioning with busulfan, etoposide and cyclophosphamide. Successful engraftment was followed by early relapse on day 67. A second HLA-identical transplant was performed following myeloablative treatment with TBI. Engraftment was once again successful and the patient remains free of disease more than 24 months after transplantation. We conclude that busulfan is insufficient in eradicating JCML and that TBI is required prior to transplantation. PMID- 2190660 TI - Treatment of refractory lymphoma with high dose cytarabine, cyclophosphamide and either TBI or VP-16 followed by autologous bone marrow transplantation. AB - This study was designed to test the efficacy and toxicity of combining high-dose cytarabine (3 g/m2 every 12 h x 8 doses day -7 to day -4, total dose 24 g/m2), methyl prednisolone (0.5 mg/kg every 4 h day -7 to day -1), and cyclophosphamide (CY) (60 mg/kg day -3 and day -2) with either total body irradiation (TBI) (900 cGy in a single fraction on day -1) or VP-16 (600 mg/m2/days -7, -5, and -3) in patients not eligible for TBI secondary to prior radiotherapy. We treated 14 patients (eight male, six female) with either non-Hodgkin's lymphoma (n = 5) or Hodgkin's disease (n = 9). All patients had failed prior conventional chemotherapy (median two regimens range 1-5). Five patients were treated with TBI and nine with VP-16. There were eight complete remissions, two partial remissions, four were inevaluable for response due to early death. Overall survival is 21% (3/14) and relapse-free survival is 7% (1/14) with the sole disease-free survivor now 40 months from transplant. Very significantly, among patients receiving TBI, there were no survivors (median survival 24 days, range 17-330 days) and 4/5 had pulmonary complications. Median DLCO in these four patients was 61% (range 50-67) prior to transplant and none had an infectious etiology established by bronchoalveolar lavage. Median time to an absolute granulocyte count of 500 x 10(6)/l was 16 days (range 10-37 days) and to a platelet count of 20 x 10(9)/l was 12 days (range 7-22 days). In conclusion, the addition of high-dose cytarabine (24 g/m2) to CY and single-dose TBI or VP-16, while being very active, produced excessive pulmonary toxicity in this group of patients with lymphoma. PMID- 2190663 TI - Focusable Doppler ultrasound in mapping dorsal hand flaps. AB - The dorsal arterial anatomy of 50 normal hands was mapped using high frequency pulsed wave Doppler ultrasound. The findings correlated with previous anatomical studies regarding the variability in the incidence of the arteries. Eight clinical cases were studied preoperatively, seven of whom underwent surgery involving local flaps. Intraoperatively the presence of the mapped vessels was confirmed in each case. This investigation defines the role of high frequency pulsed wave Doppler ultrasound in the mapping of dorsal hand flaps. PMID- 2190662 TI - Infection and rheumatic diseases: a review (2). PMID- 2190664 TI - Pretibial lacerations: a comparison of primary excision and grafting with "defatting" the flap. AB - Pretibial lacerations are often followed by slow healing. When a flap is raised, simple suture is doomed to failure and both a conservative approach and one involving skin grafting have been advocated. In this study, 25 patients with pretibial flap lacerations were randomly allocated to treatment either by primary excision and grafting or by "defatting" the flap and laying it on the defect. Healing times were compared in the two groups. Our results showed that healing time was significantly faster in the grafted group (mean 13.2 days) than in the defatted group (mean 40.7 days), Student's t test = 3.29 (p less than 0.01). PMID- 2190666 TI - Anterior scoring for bat ears; the story so far. PMID- 2190665 TI - A brief history of the development of plastic surgery in The Netherlands East Indies from World War I until the independence of Indonesia (1914-1950). AB - This study of surgical operations published in the Medical Journal of the Netherlands East-Indies over the period 1914-1950, supplemented with a series of interviews with retired Dutch East-Indian surgeons and their relatives, shows a vivid interest in plastic surgery from World War I until the independence of Indonesia. One can conclude that plastic surgery was performed more frequently and on a larger scale than in Holland, due to a larger number of patients, specific tropical pathology and often a longer patient delay, requiring extensive reconstructive procedures. The East-Indian publications on plastic surgical topics outnumber the Dutch ones enormously. PMID- 2190667 TI - Treatment of palatal fistula by expansion. AB - Treatment of a large anterior fistula of the hard palate remains a problem. A new approach is presented by expansion of the palatal mucosa by custom-made implants, allowing closure in two layers without tension or extensive undermining. PMID- 2190668 TI - Diagnostic ultrasound in the athlete's locomotor system. PMID- 2190669 TI - [Reflections on the human anatomy]. PMID- 2190670 TI - [Current strategies for the prevention of malaria]. AB - Two billion of persons live in regions where endemic malaria prevails or has reappeared. An estimated on hundred million infected individuals per year have been reported around the world. In front of this alarming situation, the diversity and even the incoherence of the currently proposed prophylactic regimens confuses the therapists and renders difficult the adoption of an efficacious strategy. The extension and gravity of drug resistance of P. falciparum and the withdrawal of anti-vectorial campaign constitute two reasons for the present recrudescence of malaria. The preventive strategies in 1990 are based on: rehabilitation of anti-vectorial campaign particularly against nocturnal mosquito bites, applicable to all, everywhere and at all times, by the means of individual and collective measures and mostly by impregnated nets; chemoprophylaxis for which two situations should be distinguished: the non immune traveler leaving for a short period (inferior or equal to 3 months) to an endemic area: individuals living permanently or for long periods in tropical regions. Prevention for short stays In low risk transmission zone (North Africa, Mexico, large cities of South East Asia) whatever the duration, suppression of chemoprophylaxis is acceptable. In high risk transmission zone, three strategies exist according to the intensity and frequency of drug resistance: zone 1 (P. vivax or drug sensitive P. falciparum): chloroquine at a dose of 100 mg/day for adults (1.5 mg/kg/day for children) 6 days out of 7, from the day of departure trough the whole stay and for one month after the return, is still efficacious; zone 2 (moderate frequency of drug resistance): protection is again ensured by chloroquine only, as in zone 1, or better than that by the association of chloroquine 300 mg once a week and proguanil 200 mg/day (3 mg/kg/day for children). The side effects of mefloquine and the risk of generation drug resistance argue against its general use in this zone particularly in West Africa. In one year, we have already observed three chemoprophylactic failures with mefloquine in individuals returning from this region; zone 3 (high frequency of drug resistance and multiresistance): mefloquine, if well tolerated is justified in weekly intake. In case of contraindications or intolerance to mefloquine, which are becoming more frequent, no substitution for that chemoprophylactic regimen is presently available. In view of these facts, indications, contraindications and posologies of mefloquine should be reviewed to better profit from the remarkable characteristics of this antimalarial. Mefloquine should only be prescribed (excluding curative treatment) for chemoprophylaxis of short stays in zone 3. Some contraindications of this drug should be maintained (pregnant women) or made relative (treatment with B-blockers and in the absence of pediatric studies, children weighing less than 15 kg).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2190672 TI - [Eulogy to Felix-Pierre Merklen (1901-1988)]. PMID- 2190671 TI - [Infections caused by Mycobacterium africanum]. AB - Mycobacterium africanum is a bacterial species that was singled out in 1969. Its biochemical and cultural characteristics are intermediary between those of Mycobacterium tuberculosis and Mycobacterium bovis. This bacteria is responsible for tuberculosis in both western and central Africa. We can distinguish between four different types dependent upon the geographical origins of the patients. The extent of this case, with multiple cutaneous and visceral lesions, could not be explained by a past or associated disease or by an immunological defect, be it congenital or acquired. PMID- 2190673 TI - The pyrazoloacridines: approaches to the development of a carcinoma-selective cytotoxic agent. PMID- 2190674 TI - What causes lymphocytic tumors? PMID- 2190675 TI - Confronting infertility and cancer. PMID- 2190677 TI - An overview of tumor biology. PMID- 2190678 TI - Autologous marrow transplantation for Hodgkin's disease current techniques and prospects. AB - Hodgkin's disease is a chemotherapeutically curable malignancy, but cure is rare if a complete remission is not achieved with initial therapy. Drugs that have myelosuppression as a major dose-limiting toxic effect, can be given at high doses and may be combined together at close to the maximum tolerated dose with marrow rescue. Multiple chemotherapy drugs given at high doses with marrow rescue are best utilized if they possess dissimilar extramedullary toxicity. The use of growth factors and improved storage methods may also help reduce hematopoietic toxicity. There is currently no consensus on the ideal treatment regimen, although combinations of etoposide, carmustine, and cyclophosphamide are frequently used and are associated with decent disease-free survival. The frequency of pulmonary complications is higher with regimens containing higher doses of carmustine. There are no prospective comparative randomized trials between standard chemotherapy and high dose chemotherapy with marrow support. Patients transplanted earlier in the course of their disease appear to do best, as do patients with good performance status and low tumor burden who have had less than two prior regimens. In such patients the long-term disease-free survival after autologous bone marrow transplantation may be in excess of 80%. Patients with Hodgkin's disease refractory to front line chemotherapy do poorly with high dose chemotherapy with autologous marrow rescue and often do not achieve remission. Newer regimens need to be explored and developed for patients at high risk of relapse. PMID- 2190676 TI - Vincristine infusion with CHOP-CCNU in diffuse large-cell lymphoma. AB - Phase I and II trials of vincristine infusion have demonstrated the safety and efficacy of this approach in the treatment of patients with refractory non Hodgkin's lymphoma. Subsequently, a trial was designed to evaluate this technique in untreated patients. Repeated 5-day infusions of vincristine 0.25 mg/m2 per day were incorporated into a CHOP-CCNU regimen and administered to 24 patients with advanced diffuse large-cell lymphoma. Objective responses occurred rapidly and were observed in 18 (75%) patients in whom 13 (54%) were complete. Toxicity was generally mild to moderate and neurotoxicity appeared to be no worse than typically observed with bolus vincristine. Complete responses have been durable in most patients and 10 (77%) of the complete responders have not relapsed. At this time, 9 (38%) of the total patients remain alive and without evidence of disease from 3.8 to 7.3 years from the start of treatment. One patient died of disseminated gastric cancer at 3.3 years from the start of therapy and there was no evidence of lymphoma at exploratory laparotomy. Infusion of vincristine may be safely incorporated into multiagent chemotherapy programs of the CHOP type for non-Hodgkin's lymphoma. Its potential for protracted nonmyelosuppressive cell kill would appear attractive in designing future trials for this disease. PMID- 2190679 TI - Stem cell potential of ductular and periductular cells in the adult rat pancreas. PMID- 2190680 TI - Specification of notochord cells in the ascidian embryo analysed with a specific monoclonal antibody. AB - Among 40 notochord cells of an ascidian tadpole larva, 32 notochord cells originate from the anterior-vegetal blastomeres (the A4.1 pair) of an 8-cell embryo and eight cells originate from the posterior-vegetal blastomeres (the B4.1 pair), but the animal blastomeres (the a4.2 and b4.2 pairs) are not engaged in the formation of the notochord. If four pairs of cells, separated from an 8-cell embryo, were allowed to develop into quarter embryos, expression of the notochord specific antigen was evident in the A4.1 and B4.1 quarter embryos. Embryos, in which cytokinesis had been permanently blocked at the 8-cell and later stages with cytochalasin B, were found to develop the notochord-specific antigen only in the presumptive notochord cells. These findings suggest the developmental autonomy of presumptive notochord cells in the ascidian embryo. PMID- 2190681 TI - Continuous arteriovenous hemofiltration/dialysis. PMID- 2190682 TI - Parathyroid localization. PMID- 2190683 TI - Heparin-associated thrombocytopenia and thrombosis: optimal therapy with ancrod. AB - Heparin-associated thrombocytopenia and thrombosis (HATT) is an infrequent occurrence but may have disastrous consequences. Continued therapy with heparin must be avoided and anticoagulation achieved by alternative means. Among the few alternatives to heparin in critically ill patients, the best is ancrod. Depletion of fibrinogen with ancrod results in anticoagulation comparable to therapy with heparin within 12 hours. In a small series, nine patients with HATT were treated with ancrod; one underwent angiographic assessment, angioplasty and subsequent vascular reconstruction. Ancrod therapy was not associated with bleeding complications. It appears to provide optimal therapy for patients suspected of having HATT. PMID- 2190684 TI - Evaluating dementia: what price testing? PMID- 2190685 TI - Guidelines for the detection of high-risk lipoprotein profiles and the treatment of dyslipoproteinemias. Canadian Lipoprotein Conference Ad Hoc Committee on Guidelines for Dyslipoproteinemias. AB - Elevated plasma levels of cholesterol and triglycerides, low levels of high density lipoproteins, hypertension, diabetes mellitus, smoking and abdominal obesity are risk factors for coronary heart disease (CHD) and stroke. Because of the preventable threat to life, well-being and productivity from perturbations of plasma lipoproteins (which affect about 60% of adults), we recommend a population based strategy with public education on diet, exercise and the hazards of smoking and legislation for better food labelling. This should be combined with the medical guidelines we describe to detect and treat those at highest risk for CHD (including about 15% of adults), who merit priority for the medical, dietetic and laboratory services required. Among people aged 40 years or more this includes those with plasma total cholesterol levels greater than 7 mmol/L, fasting triglyceride levels greater than 3 mmol/L or cholesterol level greater than 6 mmol/L when associated with CHD or other risk factors for CHD. For younger people the criteria for highest risk include cholesterol levels greater than 6.5 mmol/L for those aged 30 to 39 years, greater than 6 mmol/L for those aged 20 to 29 and greater than 5 mmol/L for those under age 20. PMID- 2190687 TI - Effect of antioxidants on the mitochondrial activity and toxicity of the cancer drug methylglyoxal bis (guanylhydrazone) in yeast and mammalian cells. AB - Mitochondria of yeast cells were primary targets of methylglyoxal bis (guanylhydrazone) (MGBG) from the following criteria: (1) selective inhibition of growth of cells utilizing a non-fermentable energy source, (2) inhibition of mitochondrial protein synthesis compared with cytosolic protein synthesis and (3) selective mutagenesis of the mitochondrial genome compared with nuclear mutagenesis. Evidence of primary antimitochondrial activity of MGBG in mammalian cells was provided by greater potency of the drug in guinea pig keratinocyte cultures utilizing glutamine as carbon and energy source compared with fermentable glucose. Cell death was used as a measure of drug toxicity in both yeast and mammalian systems. The antioxidants glutathione, vitamin E and vitamin C reversed toxicity and antimitochondrial activity to a large extent implying that toxic free radical metabolites of the drug are of significance in cellular activity of MGBG. PMID- 2190686 TI - Recommendations of the Canadian Consensus Conference on Non-Pharmacological Approaches to the Management of High Blood Pressure, Mar. 21-23, 1989, Halifax, Nova Scotia. PMID- 2190688 TI - High sensitivity of the LEC rat liver to the carcinogenic effect of diethylnitrosamine. AB - The initiation sensitivity of the liver of the LEC (Long-Evans with a cinnamon like coat color) rat, a new mutant strain with a high incidence of spontaneous liver tumors, was studied by treatment with low doses of diethylnitrosamine (DEN) coupled with modified Solt and Farber's selection. LEC and control LEA (Long Evans with an agouti coat color) rats received i.p. injections of 10 mg/kg of DEN, then selected by feeding with a diet containing 0.02% 2-acetylaminofluorene (AAF) for 7 days combined with partial hepatectomy (PH). The numbers of placental glutathione S-transferase (GST-P)-positive foci in the livers of LEC rats were 10 times higher than those in LEA rats. These results suggested a high sensitivity of the LEC rat liver to the carcinogenic effect of DEN. The association between initiation sensitivity and spontaneous liver-tumor development and the possible usefulness of the LEC rat for in vivo short-term tests of hepatocarcinogens are discussed. PMID- 2190689 TI - [Compensation in diabetes and serum insulin levels in type I diabetics during insulin pump therapy and after changing to treatment with a combination of short- and long-acting insulin]. AB - Twenty-one type diabetics previously treated in the conventional way with insulin with unsatisfactory results were admitted to hospital. The blood sugar level, serum insulin and non-esterified fatty acids in serum (NEFA) were assessed from 6 a.m. to 2 a.m. during treatment with an insulin pump and after changing the patients to insulins with varying length of action. Patients in the following groups were followed up separately: a) patients with antibodies against insulin treated either by two (n = 4) or three (n = 12) injections; b) patients with antibodies (n = 16) and without antibodies (n = 5), regardless of the number of insulin injections. Changes from the insulin pump regime implied an increased insulin requirement, (significant only in group b) and deteriorated compensation of diabetes which was more markedly manifested when evaluated by index M according to Schlichkrull with the exception of the group without antibodies, where M remained despite the increase in the range of satisfactory compensation. The NEFA profile behaved in a reversed manner, as compared with the serum insulin level. The results confirm the greater success of insulin pump treatment when attempting to maintain the blood sugar level as close as possible to normal values. From the analysis of the blood sugar and serum insulin profile recommendations for the tactics of treatment are derived, when the use of an insulin pump is not possible. PMID- 2190690 TI - A pathway for generation and processing of double-strand breaks during meiotic recombination in S. cerevisiae. AB - We have identified and analyzed a meiotic reciprocal recombination hot spot in S. cerevisiae. We find that double-strand breaks occur at two specific sites associated with the hot spot and that occurrence of these breaks depends upon meiotic recombination functions RAD50 and SPO11. Furthermore, these breaks occur in a processed form in wild-type cells and in a discrete, unprocessed form in certain nonnull rad50 mutants, rad50S, which block meiotic prophase at an intermediate stage. The breaks observed in wild-type cells are similar to those identified independently at another recombination hot spot, ARG4. We show here that the breaks at ARG4 also occur in discrete form in rad50S mutants. Occurrence of breaks in rad50S mutants is also dependent upon SPO11 function. These observations provide additional evidence that double-strand breaks are a prominent feature of meiotic recombination in yeast. More importantly, these observations begin to define a pathway for the physical changes in DNA that lead to recombination and to define the roles of meiotic recombination functions in that pathway. PMID- 2190692 TI - ras and GAP--who's controlling whom? PMID- 2190691 TI - Identification of a major keratinocyte cell envelope protein, loricrin. AB - During epidermal cell cornification, the deposition of a layer of covalently cross-linked protein on the cytoplasmic face of the plasma membrane forms the cell envelope. We have isolated and characterized cDNA clones encoding a major differentiation product of mouse epidermal cells, which has an amino acid composition similar to that of purified cell envelopes. Transcripts of this gene are restricted to the granular layer and are as abundant as the differentiation specific keratins, K1 and K10. An antiserum against a C-terminal peptide localizes this protein in discrete granules in the stratum granulosum and subsequently at the periphery of stratum corneum cells. Immunofluorescence and immunoelectron microscopy detect this epitope only on the inner surface of purified cell envelopes. Taken together, these results suggest that it is a major component of cell envelopes. On the basis of its presumed function, this protein is named loricrin. PMID- 2190693 TI - Mitochondrial diseases: gene mapping and gene therapy. PMID- 2190694 TI - The NUP1 gene encodes an essential component of the yeast nuclear pore complex. AB - Monoclonal antibodies generated against a family of related nuclear pore complex proteins (nucleoporins) from rat liver nuclei cross-react with several proteins in the yeast S. cerevisiae and show punctate nuclear envelope staining similar to the pattern seen in mammalian cells. We have cloned a gene encoding one of these proteins (NUP1) and have confirmed the localization of the NUP1 protein to the pore complex by immunofluorescence, using an epitope-tagged construct to differentiate it from other members of this family. The NUP1 protein is essential for cell viability, and overexpression from the yeast GAL10 promoter prevents further cell growth. The central domain of NUP1 consists of a series of degenerate repeats similar to those found in the nucleoskeletal protein NSP1, a protein that cross-reacts with monoclonal antibodies against NUP1. We propose that the repetitive domain is a feature common to the nucleoporins. PMID- 2190696 TI - [The immunologic etiology of EPH gestosis]. PMID- 2190695 TI - [Detection of Chlamydia trachomatis in clinical material 1985-1988]. AB - Investigation of 529 smears from the uterine cervix of women before delivery, during the puerperium and before induced abortion revealed positive findings in 25.2% of women before delivery and in 19.3% of women before induced abortion. Perinatal infection was confirmed by a positive finding of Ch. t. in 12.8% neonates with conjunctivitis and 15.4% from the nasopharynx. The direct immunofluorescent method was used. In another group of women examined by the serological method ELISA, from a total of 182 sera in 41.7% the presence of IgG antibodies was detected. In cervical smears from 10 seropositive women in seven Ch. t. was positive. PMID- 2190697 TI - [Prenatal ultrasonic diagnosis of congenital developmental defects. II. Pathology of the abdomen, genitourinary tract, skeleton]. PMID- 2190698 TI - [New findings on essential amino acids]. PMID- 2190699 TI - [The effect of polyunsaturated fatty acids on the effect and binding of insulin in the fat cells of rats with genetically determined hypertriglyceridemia]. PMID- 2190700 TI - [An important representative of the Prostej health service in the past, Dr. Jaroslav Mathon]. PMID- 2190701 TI - [Modern concepts of Chinese medicinal herb (henbane) therapy]. PMID- 2190702 TI - [Antibiotic resistance of strains of Shigella dysenteriae and flexneri isolated in Tananarive and on the east coast of Madagascar]. AB - From November 1988 to March 1989, stools from 804 Malagasy children were examined, thirty-seven strains of Shigella were isolated, from which 5 S. dysenteriae serotype 1 (= Shiga bacillus) strains were found to be resistant to ampicillin, carbenicillin, streptomycin, chloramphenicol, tetracycline, sulphonamide and even to trimethoprim. Resistance to trimethoprim has appeared only recently in Madagascar. PMID- 2190703 TI - [Cross resistance to mefloquine and halofantrine in a case of P. falciparum malaria contracted in Sierra Leone]. AB - Malaria caused by P. falciparum occurred during prophylaxis with mefloquine upon return from Sierra Leone (zone II). A typical and not recognized, with negative results of initial hematological examinations. Diagnosed on D.26 with parasitemia of 0.2%. Successful treatment of clinical symptoms with halofantrine but increased anemia and positive parasitemia at D.7. Successful treatment with chloroquine. Chemosensitivity tests confirmed sensitivity to chloroquine, threshold sensitivity to quinine (IC50 = 297), resistance to mefloquine (IC50 = 76) despite high levels in bloods, and to halofantrine (IC50 = 7-laboratory normal value = 1). This cross-resistance of P. falciparum originating from Sierra Leone to mefloquine-halofantrine seems to be the first observation of this danger in Africa. Prescription of chloroquine is still imperative in zone 11 countries. PMID- 2190704 TI - [Uncomplicated attack of malaria in an area with high resistance to chloroquine. I. Evaluation of a short treatment with quinine]. AB - The good results achieved in the treatment of malaria with a 7 and 5 days one of quinine (orally dose 8 mg/kg/8 h), incited the authors to try a 3 days long treatment at the same dose. They experimented this protocol on hospitalised children. All patients were free of parasites at day 7 with an average residual concentration quinine of 2.7 +/- 0.8 mg/l. Among the 7 patients with malaria at day 14, 4 didn't require another treatment and 2 presented new infestation. 50% of plasmodial isolated strains were chloroquine resistant and 40% amodiaquine resistant. The efficiency of this protocol could be in favour of its larger use. PMID- 2190705 TI - [Uncomplicated malaria attack in an area with high chloroquine resistance. 2. Evaluation of first-choice therapeutic scheme]. AB - The authors evaluate the comparative efficiency of chloroquine and amodiaquine (35 mg/kg during 3 days) for uncomplicated malaria treatment in an area with high chemoresistance level. 236 patients with malaria were examined and treated. 38% of them previously used antimalarials. The increase dosage in comparison with the WHO recommendations (25 mg/kg), lead to no advantages for chloroquine treatment (50% failure), in contrast with amodiaquine (4% failure). Therefore amodiaquine might be preferred in the health field unit for uncomplicated malaria. PMID- 2190706 TI - [Uncomplicated malaria attack in an area with high resistance to chloroquine. 3. The use of second-choice oral drug treatment]. AB - This study appreciated the efficiency of uncomplicated malaria second line treatment (P. falciparum) in an area with high level of chemoresistance. No therapeutic failure was found with sulfadoxine-pyrimethamine (Fansidar), and mefloquine-sulfadoxine-pyrimethamine (Fansimef), in contrast with a rate of 8% with quinine. The authors discuss the place of these therapeutic, in the treatment of malaria. PMID- 2190707 TI - [Candida albicans uveopapillitis. Diagnostic and therapeutic discussion apropos of a case]. AB - Due to the difficulties encountered in the etiologie diagnosis of papillo uveitis along with the increasing occurrence of fungal infections (in paralleled with the number of AIDS affected patients), we found of interest to report a case of exsudative macular chorioretinitis with poor evolution under steroid therapy. In this patient infection by Candida Albicans was suspected and confirmed only after isolation and culture of the fungal from a vitrectomy specimen. A therapeutic apponch using Fluconazole (Triflucan allowed a dramatic improvement of visual acuity within a few months. Thus, vitrectomy appears as a decisive step in the diagnosis of endogenous ocular candidiasis. This diagnosis is even more difficult to suspect in patient without immun deficiency more any extraocular focal infestation. PMID- 2190708 TI - [Symptomatologic value of dissociated vertical divergence in concomitant strabismus]. AB - D.V.D. is an opto-motor anomaly which is likely starting from the retina. D.V.D. is seldom isolated and it is most often found in congenital strabismus or in early onset strabismus (with or without alterared fusion) with an horizontal deviation most often associated with a vertical syndrome. The clinical assessment of D.V.D. is of major importance in the pre and post-operative examination. The simultaneous horizontal and vertical surgery reduces the amplitude of D.V.D by re establishing a central or peripherical fusion. PMID- 2190709 TI - 4-Hydroxynonenal interacts with tubulin by reacting with its functional -SH groups. AB - 4-Hydroxynonenal, which is one of the most important products of lipid peroxidation, alters microtubular organization and structure in 3T3 fibroblasts. Changes in cell shape and the disappearance of microtubules are observed by immunofluorescence after incubation with the aldehyde, and the colchicine binding activity of tubulin from 3T3 cells is modified. Moreover, the aldehyde determines a decrease in the ability of purified tubulin to polymerize and to bind colchicine. These effects may be related to the interaction of the aldehyde with functional -SH groups of tubulin which are necessary for protein integrity and functions. Indeed, the addition of cysteine protects against the damaging effects of the aldehyde. PMID- 2190710 TI - Current concepts on the adult respiratory distress syndrome. AB - The shock- and trauma-induced process known as ARDS remains a major cause of mortality and morbidity. The time course of the clinical disease has changed dramatically as support systems have improved. In addition, it is becoming increasingly clear that ARDS is part of an inflammation-induced systemic disease state which can evolve to multi-system organ failure. It is MSOF which is now the leading cause of death in the post-trauma patient in the ICU. ARDS from shock and trauma must now be studied not solely as a primary pulmonary process but as a critical component of a generalized inflammatory reaction to distant tissue trauma. PMID- 2190711 TI - Effect of systemic endotoxin on skeletal muscle vascular conductance during high and low adrenergic tone. AB - The objective of this study was to determine the role of adrenergic tone on the peripheral vascular decompensation reported to occur during systemic endotoxemia. An in situ constant-flow double-canine gracilis muscle (GM) preparation allowed one GM to serve as an innervated control (GMc) for the contralateral denervated muscle (GMe). Group I (n = 9): normal inherent vascular tone; Group II (n = 7): adrenergic tone elevated by bilateral common carotid artery ligation. The GMc Group II vascular conductance was significantly lower than GMe at .0485 +/- .004 ml/min/100 g/mm Hg and .0636 +/- .005 ml/min/100 g/mm Hg respectively. GM denervation had no significant effect on Group I conductance suggesting a low level of baseline intrinsic adrenergic tone; however, denervation did increase the vascular conductance by more than 30% from .0485 +/- .004 to .0638 +/- .008 ml/min/100 g/mm Hg in Group II. A 2 mg/kg dose of endotoxin was infused i.v. over 30 min and data collected over an additional 60 min. The endotoxin caused a decrease in MAP from 129 +/- 5 to 73 +/- 6 mm Hg in Group I and from 177 +/- 16 to 92 +/- 14 mm Hg in Group II. both the GMc and GMe Group I GMs showed an initial increase in conductance to 115 +/- 9 and 117 +/- 8% respectively at 5 min followed by a reduction to 82 +/- 9 and 101 +/- 10% at 60 min. Group II (GMe) showed a significantly increased conductance following denervation to 125% which increased insignificantly to 140 +/- 15% at 60 min, while conductances either remained at about 100% or decreased slightly to 88 +/- 7% in the innervated Group II GMc. The data suggest that the baseline level of vascular tone may not be an important factor when evaluating the effect of systemic endotoxemia on the skeletal muscle peripheral vasculature. PMID- 2190712 TI - Sequential changes in lipid metabolism and the fatty acid profile in liver lipids during fasting and sepsis. AB - The sequential changes in lipid metabolism and in the fatty acid profile of liver lipids during fasting and sepsis were studied. Liver and blood specimens were taken from normally fed rats and from nonseptically and septically fasted rats at 5, 24, and 48 hr. Sepsis was induced by injecting live Escherichia coli bacteria intraperitoneally. Sepsis attenuated the fasting-induced increase in beta hydroxybutyrate and reduced liver and serum triglycerides at 5 hr. There was a percentage decline in the most abundant fatty acids in neutral lipids, namely oleic (18:1w9) and linoleic (18:2w6) acids. This was seen throughout fasting and septic fasting. These results indicate that 18:1w9 and 18:2w6 are used as energy substrates and are oxidized to beta-hydroxybutyrate during fasting and mainly to carbon dioxide during septic fasting. On the contrary, the most abundant fatty acids in phospholipids, stearic (18:0), arachidonic (20:4w6), and docosahexaenoic (22:6w3) acids, accumulated in neutral lipids and in phospholipids throughout fasting. However, during sepsis this accumulation was reduced in neutral lipids and reversed to a level below that in the fed and fasted state in phospholipids. These results indicate that a disturbance in membrane integrity and function induced by septic fasting may have pathophysiological consequences for lipid metabolism and liver function during sepsis. PMID- 2190713 TI - Calcium fluxes in cardiac sarcolemma and sarcoplasmic reticulum isolated from endotoxin-shocked guinea pigs. AB - In vitro examination of cardiac tissues isolated from septic and endotoxin shocked animals has demonstrated intrinsic decreased contractile function and has suggested calcium-related dysfunction. Both the sarcolemma (SL) and sarcoplasmic reticulum (SR) membranes have important roles in regulating cardiac free Ca2+ concentration. Therefore, calcium fluxes were examined in well-characterized SL and SR fractions isolated from hearts of control and endotoxin-shocked guinea pigs. Calcium pump activity was similar in SL from control and shock animals. No intrinsic alteration in the rate of equilibrium calcium concentration of Na(+) Ca2+ exchange was observed in SL from shock guinea pigs. The electrogenic nature of the exchange was maintained. Active Ca2+ transport, Ca2(+)-ATPase activity, and Ca2+ efflux were similar in SR from hearts of control and shock animals. Although no intrinsic calcium dysfunction was noted in the sarcolemma or sarcoplasmic reticulum from the shock animals, this does not preclude the possibility that some factor (humoral agent) or condition (acidosis) may alter calcium processing in these membranes in vivo. PMID- 2190714 TI - The luteinizing hormone-releasing hormone (LH-RH) system in neonatally estradiol feminized male gray short-tailed opossums (Monodelphis domestica). AB - In this study, the luteinizing hormone-releasing hormone (LH-RH) system was examined in adult gray short-tailed opossums that had been treated with estradiol benzoate (EB) on days 1 and 3 of postnatal life, a treatment which results in complete block of testicular development. The finding that the organization of the LH-RH system in neonatally EB-treated males did not differ from that of neonatally untreated animals indicates that the LH-RH system can develop normally despite the absence of gonads throughout perinatal life. PMID- 2190715 TI - Neuritogenesis in cerebellar granule cells in vitro: a role for protein kinase C. AB - We have used short-term (8 h) cultures of week-old rat cerebellar granule cells to examine the effects on neuritogenesis of activation and down-regulation of protein kinase C by phorbol esters. We have previously demonstrated that endogenously released glutamate promoted neurite outgrowth in the same system acting via N-methyl-D-aspartate receptors. Low levels (0.1-1 nM) of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) evoked increases in the number of granule cells which extended neurites; higher levels (10-250 nM) which caused a down-regulation of total protein kinase C, inhibited outgrowth in a dose dependent manner. N-Methyl-D-aspartate by itself also stimulated process outgrowth but could not reverse the inhibition evoked by either TPA or the protein kinase C inhibitor sphingosine. Stimulation of protein kinase C with 0.1 nM TPA resulted in a general increase in the incorporation of 32P-labelled inorganic orthophosphate into granule cell polypeptides. The results indicate that the activation of protein kinase C is involved in neuritogenesis in granule cells and are consistent with the idea that N-methyl-D-aspartate receptor activation may exert its effect on neuritogenesis through protein kinase C. PMID- 2190716 TI - Ultrasound-guided percutaneous drainage of deep neck abscesses. AB - Deep neck abscesses may still result in significant morbidity and mortality. Surgical therapy carries the risk of damage to cranial nerves and arteries. Excellent results of ultrasound-guided percutaneous catheter drainage of abdominal abscesses led us to apply this technique to the management of deep neck abscesses. Five patients were treated with ultrasound-guided catheter drainage and antibiotics. All patients were cured without complications or recurrences. We consider this cheap and highly effective treatment as a valuable alternative to conventional therapy. PMID- 2190717 TI - Patterns and mechanisms of spread of squamous carcinomas of the oral cavity. PMID- 2190718 TI - Deficiency of distal 8p--report of two cases and review of the literature. AB - A terminal deletion in the short arm of chromosome 8 was found in a 2.5-year-old boy: 46,XY,del(8) (p22.0) and in a 1-year-old girl: 46,XX,del(8) (p23.1) with dysmorphic craniofacial features and developmental retardation. Erythrocyte GSR activities of the boy and of his parents were within normal limits. Vitamin K dependent coagulation factors in the girl and her parents gave normal results. Clinical findings were compared with previously reported cases and suggested a recognizable syndrome. PMID- 2190719 TI - Bes, Aesop and Morgante: reflections of achondroplasia. AB - The past perception of achondroplasia is reflected in art, beginning about 2000 B.C. Achondroplasia is thought to have provided a model for the representation of a series of figures including the Egyptian god Bes, the Greek teller of fables Aesop, and the Renaissance giant of fiction Morgante. Since these figures were basically viewed as good, the hypothesis is advanced that achondroplasia was perceived as a positive, not a negative, condition during at least part of the past four millenia. PMID- 2190720 TI - Repeat renal biopsy in children with IgA nephropathy. AB - Serial renal biopsy findings in 61 children with IgA nephropathy were correlated with their clinical course. At the time of the second biopsy, 23 patients showed clinical remission defined as complete disappearance of proteinuria and hematuria with normal renal function while 38 had persistent urinary abnormalities with normal renal function at the second biopsy. There were no differences between the two groups with regard to initial clinical findings and pathologic findings of the initial renal biopsy. The second biopsy of patients with clinical remission showed improvement of the glomerular changes on light microscopy, disappearance or diminution of IgA deposits in the mesangium and decrease of electron-dense deposits, whereas the second biopsy of patients with persistent urinary abnormalities showed progression of glomerular changes on light microscopy, persistence of mesangial IgA deposits and persistence of electron-dense deposits. Our study results show the importance of repeat renal biopsy in children with IgA nephropathy with persistent urinary abnormalities, as a progression of glomerular changes is common in these patients. These observations suggest that the deposition of IgA in the mesangium may be responsible for the glomerular damage in children with IgA nephropathy. PMID- 2190721 TI - The nutritional/metabolic and hormonal effects of 8 weeks of continuous ambulatory peritoneal dialysis with a 1% amino acid solution. AB - Circulating intermediary metabolites, hormones and plasma amino acids (AA) were measured at intervals over 24 hours in seven non-diabetic patients with chronic renal failure treated by continuous ambulatory peritoneal dialysis (CAPD), before and after an 8-week period during which a 1% amino acid dialysis solution replaced two of the four dextrose exchanges. Mean 24-hour concentrations of plasma total and essential amino acid were higher following the AA dialysate (total pre: 2893 +/- 185; total post: 3357 +/- 244; p less than 0.05; essential pre: 751 +/- 47; essential post: 1064 +/- 57 mumol/l; p less than 0.001). Mean 24 hour concentrations of the branched chain amino acids leucine, isoleucine and valine were higher following the AA dialysate (valine pre: 201 +/- 18; valine post: 321 +/- 19; p less than 0.001; leucine pre: 102 +/- 6; leucine post: 127 +/ 9; p less than 0.01; isoleucine pre: 67 +/- 5; isoleucine post: 85 +/- 7 mumol/l; p less than 0.05). Serum albumin increased with use of the AA dialysate (pre: 36 +/- 1; 2 weeks, 40 +/- 1; 4 weeks, 40 +/- 1; 6 weeks, 41 +/- 1; 8 weeks, 38 +/- 2 g/l). 24-hour profiles and mean 24-hour concentrations of blood glucose, serum insulin, serum triglyceride, plasma non-esterified fatty acids (NEFA), plasma 3-hydroxybutyrate and plasma alanine were unchanged after the AA period. Plasma bicarbonate decreased with use of the amino acid solution (pre: 21 +/- 1; 2 weeks, 18 +/- 1; 4 weeks, 18 +/- 1; 6 weeks, 16 +/- 1; 8 weeks, 16 +/- 1 mmol/l). Use of a 1% amino acid solution over an 8-week period in CAPD patients improves the plasma amino acid profile but results in a metabolic acidosis. The other endocrine and metabolic abnormalities of uremia remain unchanged. PMID- 2190722 TI - Reperfusion therapy in acute myocardial infarction: present status and controversy. AB - Coronary thrombolysis revolutionized the treatment of acute myocardial infarction. Most of the experience was obtained with intravenous use of streptokinase and tissue-type plasminogen activator, the latter being superior to streptokinase in regard to coronary recanalization. Numerous other promising thrombolytic agents are being investigated. Both streptokinase and tissue-type plasminogen activator decreased mortality in large trials; comparison studies in terms of efficacy are presently being performed (GISSI 2). Aspirin is an important adjunct to thrombolytic therapy; it decreased mortality by itself (ISIS 2). Heparin is conventionally used together with thrombolysis. Its efficacy is under study (GISSI 2). Intracranial hemorrhage is the most devastating complication of thrombolysis. With the present dosage regimens, the incidence is approximately 0.5%. Percutaneous transluminal coronary angioplasty in conjunction with thrombolysis accomplished frequent and persistent recanalization of the infarct artery with low mortality, including high risk patients. The TIMI IIB study demonstrated that the results of a "conservative strategy" with aggressive management of recurrent ischemic events were comparable to those of an "invasive strategy." Subgroup analysis should, however, be awaited. High risk patients with low ejection fraction or with shock benefit by early mechanical coronary recanalization. The role of thrombolysis in the "late" stage of transmural myocardial infarction or in the acute ischemic syndrome (unstable angina/non-Q wave myocardial infarction) is unclear and presently under investigation. PMID- 2190723 TI - Current perspectives in hypertrophic cardiomyopathy: diagnosis, clinical management, and prevention of disability and sudden cardiac death. AB - Hypertrophic cardiomyopathy is a rare primary myocardial disease known for its dramatic morphologic and clinical manifestations. Sudden cardiac death and functional cardiac symptoms are common. However, differing pathologic mechanisms may be responsible for similar clinical symptoms and make a unified approach to therapy impossible. This review will discuss the genetics, criteria for diagnosis, relationship among pathophysiologic abnormalities and clinical symptoms, and management of hypertrophic cardiomyopathy. PMID- 2190724 TI - Prognosis during one year for patients with myocardial infarction in relation to the development of Q waves: experiences from the Miami trial. AB - From a randomized multicenter trial with metoprolol in suspected acute myocardial infarction (n = 5778) we report on the outcome during a one-year follow-up in patients with confirmed infarction (n = 4106) in relation to whether or not they developed Q waves. Patients with Q waves had another pattern of risk factors, including lower age and a lower occurrence of previous infarction, angina pectoris, and congestive heart failure. After one year follow-up, 14.3% of the patients with Q waves had died versus 9.0% of those without Q waves (p less than 0.001). Reinfarction during the first year occurred in 8.2% of patients with Q waves and 12.5% of patients without Q waves (p less than 0.001). After one year, other morbidity aspects appeared relatively independent of the original presence of Q waves. In conclusion, during the first year after development of acute myocardial infarction the appearance of Q waves during the first three days is associated with a higher mortality and a lower reinfarction rate, whereas other morbidity aspects appear to be relatively independent of its presence. PMID- 2190725 TI - Prophylactic treatment after electroconversion of atrial fibrillation. AB - Atrial fibrillation is a common arrhythmia. Sinus rhythm can often be restored by electroconversion, but the relapse rate is high. Various antiarrhythmic drugs have been used to maintain sinus rhythm after electroconversion. This article reviews the experience with these drugs and suggests a treatment strategy. PMID- 2190726 TI - Allan Burns. PMID- 2190727 TI - Laboratory tests for the diagnosis of viral disease in pregnancy. PMID- 2190728 TI - The placenta and viral infections. PMID- 2190729 TI - Teratogenic viral infections. PMID- 2190730 TI - Herpes and pregnancy: new management. PMID- 2190731 TI - Antiviral therapy in pregnancy. AB - Though the reported experience with zidovudine in human pregnancies is very limited, it would seem unreasonable at this time to withhold zidovudine therapy for fetal considerations in the treatment of pregnant women with AIDS and ARC. Whether the treatment of HIV-positive women with zidovudine at any time during pregnancy reduces the risk of perinatal transmission is unknown. Therefore, the use of zidovudine for that indication should await the results of controlled trials. At present, if zidovudine therapy is required during pregnancy, the standard dosage of 200 mg every 4 hours should be used. The woman and her fetus should be monitored carefully for signs of toxicity. PMID- 2190732 TI - Prevalence and social impact of urinary incontinence in women. PMID- 2190733 TI - Anatomy and physiology of urinary continence. AB - Each of the three components of the continence mechanism, that is, proximal urethral support, internal sphincter activity, and external sphincter function, contributes to continence. Any one alone may not be able to keep a patient dry. The pressures generated during a cough may easily overcome the internal and external sphincters closing powers, and the normal supportive mechanism works in such a way as to increase closure during increases in abdominal pressure. Normal support, conversely, is not sufficient in and of itself to maintain continence, and must have sufficient resting sphincteric activity to be effective. When one element is abnormal, the other mechanisms may be able to compensate and maintain continence. It is because there are these several interdependent parts of the continence mechanism that no single urodynamic parameter is predictive of stress continence. Each different etiologic type of stress incontinence reflects the malfunction of an anatomic component of the sphincteric mechanism. Therefore, a knowledge of this mechanism's structure is fundamental to an understanding of this common clinical problem. Technologic advances in assessment of the lower urinary tract have made the separation of different types of stress incontinence possible. The further realization that each type requires different treatment has made the distinctions between these clinically important entities. PMID- 2190734 TI - Diagnosis of urinary incontinence. PMID- 2190735 TI - Cystometry, urethrocystometry, and videocystourethrography. AB - A number of techniques are available to detect detrusor overactivity. The test best suited to an individual investigator is a function of expertise, frequency of use, cost, availability, and ability to interpret the testing method. Even the simplest methods may be used effectively when the examiner understands the test and its limitations. Many investigators will find it useful to use more than one of these techniques. It is in the patient's best interest for her physician to maintain a reasonable index of suspicion and continue testing rather than submit her to inappropriate therapy based on an inadequate evaluation. PMID- 2190736 TI - Diagnostic evaluation: additional urodynamic testing. AB - There is a large array of additional urodynamic tests to be used as an adjunct to cystometry. Although each, in theory, is useful good clinical practice dictates that such testing be used only if clarification of diagnosis is needed or if a change in management due to test results is anticipated. Submitting every patient referred for urodynamic evaluation to the same battery of tests regardless of the individual's symptoms is to be discouraged. PMID- 2190737 TI - Conservative management of urethral sphincter incompetence. PMID- 2190738 TI - Surgical management of urethral sphincter incompetence. PMID- 2190739 TI - Management of recurrent genuine stress incontinence. AB - Recurrent stress incontinence is frequently a result of incomplete preoperative evaluation. Evaluation of surgical failures must include an assessment of urethral sphincter function by endoscopy, UCPP, or video-urodynamics. Patients with GSI and a mobile urethovesical junction and normal urethral closure pressure should be corrected by a Burch sling or MMK. Patients with low urethral closure pressure and normal or borderline UVJ mobility should have a suburethral sling procedure. Patients with a nonfunctioning urethral sphincter respond best to an artificial urinary sphincter. PMID- 2190740 TI - The management of detrusor instability. AB - Detrusor instability is a urodynamic diagnosis made when the detrusor is shown objectively to contract, spontaneously or on provocation, during the filling phase of a cystometrogram while the patient is attempting to inhibit micturition. It often is responsible for symptoms of urgency, frequency, nocturia, urge incontinence, and nocturnal enuresis, but is not synonymous with any of them. Furthermore, it may be responsible for urinary incontinence which appears to be simple stress incontinence, and should be excluded before an operation for genuine stress incontinence is undertaken. Patients with mixed incontinence should have their detrusor instability treated before an attempt at surgical correction of stress incontinence is made. A number of therapeutic options exist for the unstable bladder. The simplest is bladder drill. My own preference is to start patients on bladder drill in conjunction with oxybutynin chloride 5 mg orally three times daily, with the plan of weaning them off the medication if possible in 3-6 months. Propantheline bromide in dosages of 15-30 mg orally four times daily also appears to be effective. Imipramine, in dosages of 25-50 mg orally twice daily, or up to 75 or 100 mg orally at night also may be helpful, especially if the patient suffers from nocturia or nocturnal enuresis. The effects of imipramine appear to be additive to those of other drugs, and this makes it a useful adjunct in therapy. Emepronium bromide and flavoxate hydrochloride appear to be less useful pharmacologic agents. The expected addition within the next few years of terodiline hydrochloride to the drugs available in the United States is likely to improve significantly our ability to treat detrusor instability. The use of prostaglandin synthetase inhibitors in women with perimenstrual exacerbations of their symptoms may be useful on a case by-case basis. Patients who do not experience improvement with behavioral intervention and pharmacologic treatment may be candidates for electric stimulation therapy or surgery. The efficacy of electric stimulation therapy is diminished in many cases by poor patient acceptance. The most effective surgical treatment for refractory detrusor instability appears to be augmentation cystoplasty, which should be attempted only by a trained reconstructive urologist, and which should be reserved for the most refractory and difficult cases. PMID- 2190741 TI - Overflow incontinence and urinary retention. PMID- 2190742 TI - Prevention and management of urovaginal fistulas. PMID- 2190743 TI - [A case of cerebrotendinous xanthomatosis with convulsive seizures]. AB - A 35 year-old male was admitted to our hospital because of convulsive seizures. His parents are first cousins. No other members of his family have similar symptoms. He showed mental retardation since childhood. At age 14, he had generalized convulsive seizures that were intractable. Bilateral cataracts were found and extracted at age 18. He noticed bilateral swellings at Achilles tendons at around 25 years of age. Physical examination revealed bilateral swellings of Achilles tendons. Neurologically, he showed poor intellectual ability, hyperreflexia with positive Babinski's sign and cerebellar ataxia. Marked elevations of cholestanol level (53.84 micrograms/ml; normal: 2.71 +/- 0.81, n = 17) and cholestanol/cholesterol ratio (2.20%; normal: 0.16 +/- 0.05, n = 17) were detected in serum. EEG showed abnormal background activities with bursts of high voltage slow theta activities. MRI study showed high intensity lesions in globus pallidus and multiple lesions in white matter with long spin echo sequence. Oral administration of chenodeoxycholic acid improved EEG findings, serum cholestanol level and convulsive seizures. However, the MRI abnormalities remained unchanged, which suggested irreversible brain damage. We reviewed the previous reports of 144 cases of CTX. Fourteen cases had convulsive seizures. We stress that CTX is one the causes of symptomatic epilepsy. PMID- 2190744 TI - [A case of Becker muscular dystrophy presenting cardiac failure as an initial symptom]. AB - Was reported a 23-year-old man with Becker muscular dystrophy (BMD), manifesting heart failure as an initial symptom. He had admitted to a hospital because of his sudden exertional dyspnea due to dilated cardiomyopathy. Because of elevated serum CK level, he had admitted to our hospital for further clinical evaluation. His uncle and male cousin were affected by a mild progressive muscle weakness since second decades. Physically, his intelligence was slightly below the average (WAIS total IQ 71). There was a slight weakness in his pelvic and shoulder girdle muscles. Pseudohypertrophy was observed in calves and tongue. Serum CK level was markedly elevated to ten times of the upper normal limits. Both EMG and muscle biopsy examinations revealed mild myopathic changes. Electrocardiogram showed tall R waves in leads V1 and V2, abnormal Q waves in I, aVL, V5 and V6 and flattened T waves in V5 and V6. On immunostaining of the biopsied skeletal muscle, patchy appearance of dystrophin on the surface membrane of the fiber was detected, which is consistent with BMD. Myocardiac damages in BMD are not always related either to the duration or the severity of the skeletal muscle weakness, as shown in our present case. The possibility that subclinical BMD is one of causes for dilated cardiomyopathy always must be considered. PMID- 2190745 TI - Use of metoclopramide, domperidone, and cisapride in the management of diabetic gastroparesis. AB - The pathophysiology, diagnosis, and treatment of diabetic gastroparesis are reviewed, and the mechanisms of action, pharmacokinetics, clinical efficacy, adverse effects, and dosage of metoclopramide, domperidone, and cisapride are described. Diabetic gastroparesis is a state of delayed gastric emptying that reportedly affects 20-30% of diabetic patients. Symptoms include nausea, early satiety, postprandial bloating and fullness, and vomiting. Diabetic gastroparesis has been managed most successfully with drugs that stimulate gastric emptying. Of the three agents studied--metoclopramide, domperidone, and cisapride--only metoclopramide is commercially available in the United States. The clinical efficacy of metoclopramide, domperidone, and cisapride has been well documented in several placebo-controlled trials. Metoclopramide effectively decreases mean gastric emptying time, although tolerance to this stimulation of gastric emptying may develop with long-term therapy. However, symptomatic relief persists with long-term therapy because of metoclopramide's antiemetic properties. Domperidone, which has also been shown to stimulate gastric motility and to possess antiemetic properties, improves symptoms in patients suffering from diabetic gastroparesis. Cisapride appears to have continued beneficial effects on gastric motility with long-term therapy. All three agents have favorable adverse-effect profiles. Although metoclopramide is currently the first-line agent for the management of gastroparesis, domperidone and cisapride both possess properties that may make them useful alternatives in patients who are unresponsive to or cannot tolerate metoclopramide therapy. PMID- 2190746 TI - Clinical physiology: an accepted branch of physiology. AB - Clinical physiology is a branch of physiology particularly dealing with functional disturbances in disease (pathophysiology) and the integrated function of the human body in disease against the background of normal function in healthy subjects, suitable physiological methods for the study of patients--particularly for diagnostic purposes--as well as for research, and the education of medical students and laboratory assistants in these fields. Departments of clinical physiology in university hospitals form a bridge between basic physiology and many clinical specialties. Independent departments of clinical physiology developed early in Sweden due to the work of Professor Torgny Sjostrand at the Karolinska Hospital in Stockholm, and have been models of research, teaching and hospital organization which have been followed in several other countries. The International Union of Physiological Sciences (IUPS) has recognized clinical physiology as a separate branch of physiology by approving a Commission of Clinical Physiology which has contributed to the programme of this and, we hope, future congresses, as well as promote the development of clinical physiology internationally. PMID- 2190747 TI - Tracers and methods of nuclear medicine. PMID- 2190748 TI - The relationship between diet and hypertension. PMID- 2190749 TI - Dietary fish oils in the prevention and management of cardiovascular and other diseases. PMID- 2190750 TI - Assessment and management of behavioral disturbances in Alzheimer's disease. AB - In summary, AD patients and their care givers are confronted with a variety of behavioral problems that may have a devastating impact on both. It is important for physicians and other health-care providers to assess the occurrence and impact of these behaviors, and to assess and treat the broader medical and cognitive problems that are evident. Measurement tools can augment the clinical interview to give the practitioner a thorough assessment of behavioral problems. A systematic six-step approach to intervention, as well as specific recommendations for the most common and troublesome behaviors of depression and agitation, are provided. Care givers vary in their ability to cope with the problems of AD patients. Some seem to adjust naturally and to anticipate and solve problems on their own. Others need considerable guidance and may require assistance from their physician as well as referral to a psychologist or other mental health professional adept in behavioral management. Physicians must play a pivotal role in recognizing problems and providing or arranging for appropriate treatment for their AD patients and care givers. PMID- 2190751 TI - Gastroduodenal ulcers: causes, diagnosis, prevention, and treatment. AB - The precise diagnosis and duration of peptic ulcer disease can now be made endoscopically. Numerous effective medical therapies are available to treat these disorders. While the vast majority of patients respond to medical therapy with complete healing of ulcers within 4 to 6 weeks, a small percentage require longer and probably more intense treatment. A total assessment of the patient's lifestyle is important in order to achieve the best therapeutic response. Cigarette smoking is a potent negative factor for both healing and ulcer recurrence. The question of who should continue on maintenance therapy and for how long has not been answered. Certainly, the first-time ulcer patient who smokes and becomes asymptomatic on treatment requires nothing more than standard 4- to 6-week therapy and discontinuation of smoking. Patients with recurrent disease and those who have sustained complications such as bleeding or perforation probably warrant 6 to 12 months of maintenance therapy, with close follow-up thereafter. Some patients will require continuous maintenance therapy in order to remain asymptomatic. In such patients it is important to determine that the problem is, in fact, "routine" peptic ulcer disease. Ulcers associated with NSAIDs are unique in that their cause is known and, at present, their treatment is specific. Studies to date indicate that the only appropriate therapy to prevent NSAID ulcers is misoprostol, and that this drug is also effective in healing such ulcers while NSAID treatment is continued. Except for complications, few patients now need to be referred for surgical intervention. Those who are should receive the least destructive procedure possible. The efficacy of medical therapy is generally enhanced following selective and highly selective vagotomy. No patient should be referred electively to surgery without the Zollinger-Ellison syndrome being ruled out. PMID- 2190752 TI - Extracorporeal shock-wave lithotripsy. PMID- 2190753 TI - Basic therapy of rheumatoid arthritis: nonsteroidal anti-inflammatory drugs. AB - Aspirin is recommended for initial therapy of RA. If aspirin is not tolerated, an NSAID is recommended. The choice of NSAID should be based on cost, convenience, safety, and the personal experience of the physician. An adequate trial of at least 2 weeks should be completed before changing to another NSAID. Therapy should be closely monitored for adverse reactions, particularly renal and gastrointestinal effects. PMID- 2190754 TI - Oral health of workers in the modern Finnish confectionery industry. AB - The association between type of work and dental findings and the relevance of sugar dust as an occupational hazard to dental health was studied in workers producing sweets, biscuits, and bakery products, and in controls in a work environment not concerned with sugar. 298 employees, 42 +/- 11 yr of age, were investigated clinically and by means of chemical and microbiological tests of their saliva. Mean total time of work on the production line in question was 10 +/- 8.5 yr. Periodontal treatment needs increased similarly with increasing age in all subgroups. Subjects concerned with biscuit production had significantly higher DMFS values than subjects in the other groups. They also had significantly higher numbers of untreated cavities: 79.6% compared with 54.7% in those making sweets, 48.3% in bakery workers, and 62.6% in the controls not exposed to sugar. High levels of lactobacilli and Streptococcus mutans were found equally in all subgroups. Because work hygiene measurements have previously shown that sugar and flour dust concentrations were below accepted limits in the confectionery factory studied, the results do not seem to support the hypothesis that airborne sugar is an occupational dental health hazard. Some other factors need to be accounted for to explain the findings. PMID- 2190755 TI - Use of radionuclides in the diagnosis of thromboembolism of venous origin: its potential and limitations. A review. AB - The review discusses the potential and limitations of radionuclide (RN) techniques of examination in diagnosing thromboembolic disease of venous origin. The advantages and drawbacks of perfusion pulmonary scintigraphy as the most commonly used method are weighed especially with a view to the diagnosis of pulmonary embolism (PE). The need for a combined examination including inhalation scintigraphy and chest X-ray is underlined. The criteria for interpreting results of RN techniques of examination in assessing the presence of PE are defined. Of the methods used in the diagnosis of venous thrombosis, the benefits and limitations of the fibrinogen uptake test (FUT) and radionuclide venography (RNV) are pointed out. When comparing RNV with X-ray phlebography, the authors found a low sensitivity in the crural area (54%) and, on the contrary, a 100% agreement in the areas of iliac veins and the vena cava inferior. PMID- 2190756 TI - The use of radionuclide techniques for identification of severe coronary disease. PMID- 2190757 TI - Sudden infant death syndrome. PMID- 2190758 TI - Therapeutic response to a dermatologic patch and betamethasone valerate 0.1 percent cream in the management of chronic plaques in psoriasis. AB - The efficacy of a hydrocolloid dermatologic patch (Actiderm) in conjunction with topical beta-methasone valerate 0.1 percent cream was studied in outpatients with chronic plaque-type psoriasis treated for three weeks, and observed for an additional two weeks after therapy. A significant degree (p less than 0.05) of lesion resolution occurred at the site treated with the dermatologic patch plus steroid cream, whereas sites treated with either agent alone showed mild but insignificant change. It was concluded that the patch was a highly effective adjunct in the treatment of chronic plaques of psoriasis. PMID- 2190759 TI - Does 'even' function really equal health and 'periodicity' disease? Fundamental error derived from intermittent disease. PMID- 2190760 TI - Results of intensified insulin therapy in type-I diabetics receiving instruction in self-monitoring. AB - Therapeutic success in I-Type diabetes (i.e., glycaemia close to normal levels in an effort to influence favourably the onset and progression of long-term complications), two important preconditions must be met. The patient must receive instruction in safe self-monitoring so he could administer insulin under the supervision of health-care personnel, either using some of the conventional protocols or, in some cases, even unconventional intensified therapy. The aim of the latter approach is good compensation of diabetes and the well-being of a patient to whom insulin administration poses no inconvenience while sophisticated technology helps him or her to overcome stressful situations. PMID- 2190761 TI - Eikenella corrodens infection of the oral cavity as a cause of bacterial endocarditis. AB - The authors describe the case of a 24-year-old woman with valve disease. After a bout of respiratory tract infection, she was diagnosed to have bacterial endocarditis associated with mitral valve disease. The causative agents isolated included Eikenella corrodens, Streptococcus intermedius, Bacteroides oralis and Bacteroides bivius. At the same time, the patient was found to have developed IgA immunodeficiency. A complication accompanying the cardiac disease was spontaneous pneumothorax. Since antibiotic therapy had failed, the mitral valve was replaced by a prosthetic one. After the procedure, the patient had her teeth examined. The examination revealed complete destruction of tooth 36, thick layers of calculus and chronic gingivitis. E. corrodens was isolated also after microbiological examination of the patient's oral cavity. The reason for reporting on what we regard as an interesting case is that bacterial endocarditis with E. corrodens implicated as the causative agent is relatively rare; to date, polymicrobial endocarditis due to E. corrodens and other microorganisms has been described in intravenous drug addicts only. PMID- 2190762 TI - Physiologic evaluation of the anorectum. A new ultrasound technique. AB - Pelvic floor physiology is a complex area of clinical study. Continence and voiding functions are not completely understood. Incontinence is an especially underrated problem. With the use of manometry and ultrasound, anorectal physiology is evaluated and correlated with clinical dysfunction. A description of a previously undescribed ultrasound technique to evaluate anorectal angles and puborectalis function is presented. The results in 10 controls and 53 symptomatic patients with different degrees of continence dysfunction are discussed. The controls showed anal pressures and anorectal angles of 29 cm H2O and 114 degrees at rest and 67 cm H2O and 95 degrees with contraction. Six of the symptomatic patients had complete incontinence to solid stools. The results of their pressures and angles were 14 cm H2O and 151 degrees at rest and 32 cm H2O and 124 degrees with contraction. The values of this group compared with controls is significantly different (P less than 0.05). Ultrasound is helpful in assessing the pelvic floor, both subjectively and objectively. It has the advantages of avoiding radiation and allowing a longer viewing time. It is less expensive compared with radiographic proctography and the data are complementary. Ultrasound and manometry may be useful for long-term follow-up of anorectal physiology. PMID- 2190763 TI - Segmental dilatation of the colon. Report of a case and review of the literature. AB - A case of segmental dilatation of the colon involving the rectosigmoid area is presented and added to 11 cases of segmental dilatation of the colon reported previously in the literature. The clinicopathologic features, etiology, and management are discussed. PMID- 2190764 TI - Infectious enteritis. A collective review. AB - Enteric infections are a major cause of diarrhea in the United States. Pathogens can cause diarrhea by elaboration of toxins that affect the intestinal mucosa or by direct invasion of the intestinal wall. Clinical evaluation can provide important clues to aid in establishing a correct diagnosis in most patients with infectious enteritis. Appropriate cultures are necessary to confirm the diagnosis in most cases. Most types of infectious enteritis are self-limiting, but some pathogens can cause serious disease, requiring accurate diagnosis and suitable antibiotic therapy. Appropriate precautions are mandatory to prevent the spread of infectious diarrhea from occurring in the hospital environment. Dietary restrictions and appropriate hygiene should be observed during travel to foreign countries to reduce the chance of acquiring infectious enteritis. PMID- 2190765 TI - Anal ileostomy with sphincter preservation in patients requiring total colectomy for benign conditions. 1948. PMID- 2190766 TI - An early clinical account of proctalgia fugax. PMID- 2190767 TI - Differences between prebreakfast and late afternoon glycemic responses to exercise in IDDM patients. AB - Little information is available regarding the optimal timing of exercise in insulin-dependent diabetes mellitus (IDDM) patients. In this study, six IDDM patients receiving ultralente-based intensive insulin therapy were studied during 30 min of exercise (approximately 60% VO2max), before breakfast, and at 1600. On two other occasions, they were studied at rest. Plasma glucose increased from 6.7 +/- 0.4 to 9.1 +/- 0.4 mM during morning exercise (P less than 0.01). In contrast, mean plasma glucose did not change during afternoon exercise (delta = 0.3 +/- 0.5 mM, NS); however, there was a 0.3- to 1.0-mM decrease in three subjects. The observed difference in the glycemic response to exercise could not be explained on the basis of changes in plasma glucagon, growth hormone, norepinephrine, or epinephrine. Plasma cortisol was higher (P less than 0.02) in the morning than in the afternoon, and plasma free-insulin concentrations were lower (P less than 0.05). These data indicate that the risk of exercise-induced hypoglycemia is lowest before breakfast. The reason for the divergent glycemic responses to exercise is not entirely clear but may be related to the observed differences in free-insulin concentrations. Because of the lower risk of hypoglycemia, our results suggest prebreakfast exercise may be preferable for some IDDM patients receiving intensive insulin therapy. Whether these findings are relevant to patients receiving other types of insulin therapy will require further investigation. PMID- 2190768 TI - Analysis of metabolic progression to type I diabetes in ICA+ relatives of patients with type I diabetes. AB - We intensively studied 5 islet cell-antibody-positive (ICA+) first-degree relatives of type I (insulin-dependent) diabetic patients before overt diabetes. In total, 55 intravenous glucose tolerance tests (IVGTTs) and 83 fasting plasma glucose determinations were made over a maximum 4-yr period before diabetes. The 5 prediabetic relatives (not diabetic when initially studied but subsequently progressed to overt diabetes) as a group showed a progressive rise in fasting glucose (r = 0.58, P less than 0.001, slope = 23.1 mg.dl-1.yr-1) and glucose at 60 min in IVGTT (r = 0.46, P = 0.01, slope = 47.5 mg.dl-1.yr-1) beginning 1.5 yr before diabetes. During the 4.0- to 1.5-yr period before overt diabetes, no change was observed in fasting glucose or glucose at 60 min on IVGTT (fasting glucose: r = 0.21, P = 0.18, slope = 2.1 mg.dl-1.yr-1; 60-min glucose: r = 0.08, P = 0.72, slope = 2.9 mg.dl-1.yr-1). The positive predictive value for a fasting glucose greater than 108 mg/dl to be within 1.5 yr of diabetes was 100% (11 of 11 values). The negative predictive value of a stimulated insulin (1-min + 3-min insulin - 2 X basal insulin) level greater than 24 microU/ml to be greater than 1.5 yr from diabetes was 90% (9 of 10 values) and 100% (10 of 10 values) at greater than 1 yr from overt diabetes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190770 TI - Management of dyslipidemia in NIDDM. AB - Coronary heart disease is the leading cause of death among patients with non insulin-dependent diabetes mellitus (NIDDM). NIDDM patients have a high frequency of dyslipidemia, which along with obesity, hypertension, and hyperglycemia may contribute significantly to accelerated coronary atherosclerosis. Because risk factors for coronary heart disease are additive and perhaps multiplicative, even mild degrees of dyslipidemia may enhance coronary heart disease risk. Therefore, therapeutic strategies for management of NIDDM should give equal emphasis to controlling hyperglycemia and dyslipidemia. The National Cholesterol Education Program recently issued guidelines for treatment of hyperlipidemia in adults including diabetic patients. Because of the unique features of diabetic dyslipidemia, however, we suggest that certain modifications in these guidelines be made to meet specific needs of diabetic patients. For example, therapeutic goals for serum cholesterol reduction should be lower in diabetic patients than in nondiabetic subjects. Particular emphasis should be given to weight reduction in NIDDM patients. In some diabetic patients, monounsaturated fatty acids may be a better replacement for saturated fatty acids than carbohydrates. The target for cholesterol lowering should include both very-low-density lipoprotein and low density lipoprotein (LDL) (non-high-density lipoprotein) rather than LDL alone. To obtain a substantial reduction of cholesterol levels, drug therapy may be required in many patients. However, first-line drugs for nondiabetic patients (nicotinic acid and bile acid sequestrants) may be less desirable in NIDDM patients than hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors and even fibric acids. In fact, HMG CoA reductase inhibitors may be the drugs of choice for NIDDM patients with elevated LDL cholesterol and borderline hypertriglyceridemia, whereas gemfibrozil appears preferable for NIDDM patients with severe hypertriglyceridemia. PMID- 2190769 TI - Failure of nocturnal hypoglycemia to cause daytime hyperglycemia in patients with IDDM. AB - To test the hypothesis that nocturnal hypoglycemia causes postprandial hyperglycemia the next day (the Somogyi phenomenon) in patients with insulin dependent diabetes mellitus (IDDM), we studied 10 moderately well controlled patients, who were on their usual therapeutic regimens, from 2000 to 2000 on three occasions. On a control day, samples were obtained without intervention. On another day, nocturnal hypoglycemia was prevented (by intravenous infusion of glucose, if necessary, from 2200 to 0400 to keep plasma glucose levels at greater than 5.6 mM). On another day, nocturnal hypoglycemia was induced (by stepped intravenous insulin infusions between 2200 and 0200 to reduce plasma glucose levels to less than 2.8 mM). After nocturnal hypoglycemia (1.9 +/- 0.2 mM), fasting (0800), morning (0800-1100), afternoon (1200-1500), evening (1600-2000), and entire-day (0800-2000) plasma glucose concentrations were no higher than those after prevention of nocturnal hypoglycemia or sampling only. On the control day, fasting and daytime plasma glucose levels were directly related to the preceding 2200 (r = 0.723, P less than 0.02, and r = 0.762, P = 0.01, respectively) and nocturnal nadir (r = 0.714, P less than 0.02, and r = 0.728, P less than 0.02) plasma glucose concentrations. Daytime plasma glucose levels were unrelated to peak nocturnal plasma glucagon, epinephrine, norepinephrine, growth hormone, or cortisol concentrations. We conclude that nocturnal hypoglycemia does not appear to cause clinically important daytime hyperglycemia in patients representative of most patients with IDDM. PMID- 2190771 TI - Extreme hyperglycemia and hyperosmolarity. PMID- 2190772 TI - Psychological impact of islet cell-antibody screening. Preliminary results. AB - The identification of at-risk individuals before the onset of insulin-dependent diabetes mellitus with islet cell-antibody (ICA) screening programs could have significant psychological sequelae. We initiated a descriptive study of ICA+ subjects and their family members in which reactions to study participation, anxiety, and coping responses are monitored. Described here are preliminary results from 18 ICA+ youngsters, 6 ICA+ adults, and their family members. ICA+ identification resulted in clinically significant anxiety that dissipated to normal levels over time for all participants. Both ICA+ subjects and family members coped with the news in similar ways, relying primarily on problem-focused and social-support coping strategies. Few blamed themselves for their own or their loved one's ICA+ status. There was some evidence that the ICA+ participants may minimize the potential impact of their at-risk status. Compared with family members, ICA+ subjects used more avoidance coping strategies, and few believed they would ever develop diabetes. In contrast, many family members believed their loved one would ultimately develop diabetes. Although the initial findings support the resiliency of this population, the long-term effects of ICA screening remain to be seen. PMID- 2190773 TI - Hypoglycemia risk during exercise after intramuscular injection of insulin in thigh in IDDM. AB - The influence of bicycle exercise (60% of W170 [working capacity at a pulse rate of 170 beats/min]; 40 min) on the absorption of 125I-labeled fast-acting insulin (10 U; Actrapid human insulin) after intramuscular compared with subcutaneous injection in the thigh was studied on 2 consecutive days in 10 insulin-dependent diabetes mellitus (IDDM) patients. Insulin absorption was measured as disappearance of radioactivity (1st-order elimination rate constants) by continuous external monitoring and as appearance of plasma free immunoreactive insulin (IRI). Subcutaneous adipose tissue blood flow (ATBF) and skeletal muscle blood flow (MF) were measured concomitantly in the contralateral thigh with the 133Xe wash-out technique. Plasma glucose was determined intermittently. The rate constant for 125I-insulin increased during exercise from 0.46 +/- 0.08 to 1.17 +/ 0.14%/min after intramuscular injection (P less than 0.001) and from 0.31 +/- 0.05 to 0.45 +/- 0.09%/min (NS) after subcutaneous injection. The rate constant of 125I-insulin from muscle remained elevated during the 80-min recovery period. The peak plasma free-IRI value was 39 mU/L higher, the area under the IRI curve was approximately 80% greater, and the decrease in plasma glucose was approximately 2 mM greater after intramuscular injection. Whereas MF increased fivefold, ATBF did not rise significantly during exercise. The results demonstrate that intramuscular compared with subcutaneous thigh injection of insulin followed by bicycle exercise induces a marked increase in insulin absorption and a substantial fall in plasma glucose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190774 TI - Incidence and significance of islet cell antibodies in women with previous gestational diabetes. AB - Islet cell antibodies (ICAs) are markers for patients at risk for insulin dependent diabetes and are associated with progressive beta-cell destruction. This prospective study was performed to estimate the incidence of these antibodies in 187 women with previous gestational diabetes. With a specific protein A monoclonal antibody (MoAb) assay, the incidence of ICAs was only 1.6% (3 of 187). Oral and intravenous glucose tolerance tests were performed in these 3 women and compared with 6 women with previous gestational diabetes without ICAs and 5 control women. Glucose tolerance was impaired only in the 3 women with ICAs, who also had an increase (P less than 0.03) in fasting plasma glucose and a decrease (P less than 0.03) in early first-phase insulin response. We conclude that the more specific MoAb method indicates a lower incidence of ICA in women with a history of gestational diabetes than previously reported and that a decreased first-phase insulin response is associated with the presence of ICAs, suggesting progressive islet cell damage. PMID- 2190775 TI - Evidence for elevated glucose threshold in patients with impaired glucose tolerance and symptoms of hypoglycemia during OGTT. AB - We evaluated the relationship between hypoglycemic symptoms, glucose nadir levels, and hormone changes in patients with impaired glucose tolerance (IGT) after an oral glucose tolerance test (OGTT). The peak counterregulatory hormone response was determined at the glucose nadir identified by continuous glucose monitoring. Eight patients with IGT who had symptoms and signs typical of hypoglycemia at the glucose nadir were compared with completely asymptomatic subjects (5 IGT patients and 13 patients who had normal glucose tolerance [NGT]). The mean glucose nadir of symptomatic IGT patients was 3.50 +/- 0.46 mM, which was not statistically different from the mean of asymptomatic NGT patients (4.10 +/- 0.56 mM) but was significantly lower than that for asymptomatic IGT patients (5.10 +/- 0.81 mM, P less than 0.001). Seven of 8 symptomatic IGT patients had glucose levels that never fell below the range of glucose nadirs for asymptomatic NGT patients. However, the symptomatic IGT group had significantly higher levels of growth hormone, cortisol, epinephrine, and norepinephrine than the asymptomatic groups in response to the nadir. We conclude that patients with IGT are capable of experiencing signs and symptoms of hypoglycemia at physiological glucose levels during OGTT with reflex stimulation of counterregulatory hormone release. This may indicate that symptomatic IGT patients have a higher glucose threshold for eliciting characteristic hypoglycemic symptom episodes than individuals with NGT. PMID- 2190777 TI - Hypoglycemia and employment/licensure. PMID- 2190776 TI - Pancreatic C-peptide response to oral glucose in fibrocalculous pancreatic diabetes. Improvement after treatment. AB - beta-Cell function (plasma C-peptide) in 17 fibrocalculous pancreatic diabetic (FCPD) subjects (14 newly diagnosed) was not different at presentation from that in 14 matched insulin-dependent diabetic subjects. After insulin treatment and improvement in the patients' nutritional and metabolic status, fasting and postglucose plasma C-peptide concentrations showed a significant increase (fasting 0.06 +/- 0.01 to 0.17 +/- 0.03 nM, peak 0.11 +/- 0.02 to 0.29 +/- 0.06 nM, mean +/- SE; P less than 0.01 for both). Thus, severely diminished beta-cell function in FCPD is partially reversible after treatment. This could contribute to the clinical metabolic peculiarities of this group of patients. PMID- 2190778 TI - Human insulin and hypoglycemia unawareness. PMID- 2190779 TI - Insulin as risk factor for vascular disease. PMID- 2190780 TI - Trends in treatment among unselected geographically defined diabetic population. PMID- 2190781 TI - Extreme insulin resistance due to anti-insulin receptor antibodies: a direct demonstration of autoantibody secretion by peripheral lymphocytes. AB - A 59-year-old woman with systemic lupus erythematosus was found to have marked hyperglycemia, extreme insulin resistance and abnormally high plasma immunoreactive insulin. Her circulating erythrocytes displayed a dramatic decrease of 125I-labeled insulin binding. Both the whole serum and purified IgG fraction strongly inhibited the binding of radiolabeled insulin to control erythrocytes. These results suggested, although indirectly, the existence of antibodies to insulin receptors in the serum of the patient. To directly investigate this issue, we used an enzyme-linked solid-phase immunoassay which allows the detection and enumeration of lymphocytes secreting antibodies towards insulin receptors. Peroxidase-conjugated anti-human immunoglobulin is used to reveal the binding of antibodies to insulin receptor-coated dishes. We demonstrated that the patient's mononuclear cells, when briefly incubated in Petri dishes with partially purified insulin receptor, were able to secrete immunoglobulins of G class specifically directed to the antigen. Moreover, only a fraction of the whole population of anti-insulin receptor antibodies was directed towards the insulin binding region of the receptor, seemingly corresponding to the auto-antibodies detected with conventional binding-inhibition assay. PMID- 2190782 TI - Islet cell surface antibodies preferentially inhibit glucose-stimulated insulin release in vitro. AB - The effect of islet surface antibodies (ICSA) on in vitro insulin release was studied. Isolated rat islets were incubated in the presence of immunoglobulin preparations from patients with insulin-dependent and non-insulin-dependent diabetes mellitus (IDDM, NIDDM) and healthy subjects, and stimulated with D glucose, L-arginine or tolbutamide. After incubation, the amount of insulin release from the rat islets was determined. The immunoglobulin preparations from 5 newly diagnosed IDDM patients who were positive for ICSA, and from 5 age matched healthy subjects were examined. Even in the absence of complement or lymphocytes, immunoglobulin fractions positive for ICSA significantly inhibited low and high concentrations of glucose-stimulated insulin release compared with normal control (P less than 0.02), but had little influence on insulin release after stimulation with tolbutamide. Arginine-stimulated insulin release was almost the same in ICSA-positive immunoglobulin fractions and the control. Immunoglobulin fractions negative for ICSA either from four patients with recently diagnosed IDDM or from four newly diagnosed NIDDM patients had only negligible effect on insulin release after stimulation with glucose. These results suggest that ICSA in IDDM patients, even in the absence of complement or lymphocytes, may preferentially interfere with the mechanisms of glucose stimulated insulin release in the pancreatic B cells. PMID- 2190783 TI - Prior long term glycaemic control and insulin therapy in insulin-dependent diabetic adolescents with microalbuminuria. AB - Adolescence seems to be a period of increased risk for the initiation of diabetic renal disease in insulin-dependent diabetic children. Poor glycaemic control is a risk factor for diabetic nephropathy. We have therefore evaluated prior long-term glycaemic control in 23 diabetic adolescents with microalbuminuria (albumin excretion rate (AER) 20-200 micrograms/min, median 39.0 micrograms/min) and in 23 matched diabetic controls with AER less than 20 micrograms/min (median 9.3 micrograms/min). Glycaemic control was assessed by mean HbA1 and clinic blood glucose levels over a period ranging from 12 to 84 months (median 48 months). Mean HbA1 was 13.6 +/- 2.0% in the microalbuminuric subjects, compared to 11.5 +/ 2.2% in the controls (P less than 0.002); mean blood glucose levels were 13.5 +/ 3.0 and 11.4 +/- 3.0 mmol/l, respectively (P less than 0.02). There appeared to be a 'threshold effect' (mean HbA1 greater than 12.0%), above which the development of microalbuminuria was more likely. More patients with microalbuminuria than controls had been treated with a single rather than twice daily insulin injections (P less than 0.001), and glycaemic control was significantly worse in patients treated with one injection. We conclude that poor long term glycaemic control is a risk factor for microalbuminuria, and that improving control during childhood is likely to reduce the prevalence of later microalbuminuria. Two insulin injections, of combined intermediate and short acting preparations, are more likely to provide better control than a single daily insulin dose. PMID- 2190784 TI - Diurnal variation in glucose and leucine metabolism in non-insulin-dependent diabetes. AB - Glucose and leucine metabolism were investigated in 5 poorly controlled non insulin-dependent diabetics (NIDDM) following an i.v. injection of 3-[3H]glucose and 1-[14C]leucine in the morning and evening. In the morning glucose concentration (11.2 +/- 0.8 mmol/l) (mean +/- SEM) and production rate (14.2 +/- 1.3 mumol/min/kg) were significantly greater (P less than 0.001, P less than 0.05) and glucose metabolic clearance rate (MCR) (1.3 +/- 0.2 ml/min/kg) significantly lower (P less than 0.05) than in a group of control subjects. Glucose concentration was lower in the evening (P less than 0.05) as a result of a decrease in glucose production rate (P less than 0.05). Leucine concentration and production rate were not significantly different from normal but leucine oxidation rate was increased (P less than 0.05). There was no diurnal variation in leucine metabolism. Since leucine production is a measure of protein breakdown, the higher morning glucose production rate was not due to an increased supply of gluconeogenic precursors from protein catabolism. PMID- 2190785 TI - Plasma glucagon responses in tropical fibrocalculous pancreatic diabetes. AB - Plasma insulin and glucagon responses to a glucose load were measured in a group of patients with fibrocalculous pancreatic diabetes (FCPD) and compared with patients with noninsulin-dependent diabetes mellitus (NIDDM) and control subjects. Both diabetic groups had markedly diminished insulin responses but the differences between FCPD and NIDDM groups were not significant. In control subjects, in response to the glucose load, plasma glucagon levels decreased while they increased in NIDDM patients. In FCPD patients there was no significant change in glucagon levels in response to the glucose load. The study shows that FCPD patients lack pancreatic alpha-cell responses to a glucose load. This may play a role in protecting these patients against ketosis. PMID- 2190786 TI - [Review article: colostral leukocytes and their significance for the immune system of newborns]. AB - The colostrum contains a comparably high concentration of leukocytes as the peripheral blood. The majority of them are vital leukocytes, namely neutrophils, macrophages and lymphocytes. There is some evidence in mouse and man that lymphocytes from the gut-associated lymphoid tissue home selectively to the peripartal mammary gland. The phagocytic cells may be involved in the transportation of certain immunoglobulins into the neonate. In vitro colostral leukocytes exhibit a variety of immunological activities such as blastogenesis after mitogenic and antigenic stimulation, cytotoxicity and phagocytosis, but the medium milk confines these activities in comparison with those of blood leukocytes. Intact colostral leukocytes reach the gut of the gut of the newborn and may even cross the intestinal wall, gaining access to the neonates system and influencing its immunologic reactions, e.g. hypersensitivity and antibody formation. The knowledge on the significance of colostral leukocytes for the protection against infection of the neonate is still limited. PMID- 2190787 TI - Brief cytochalasin-induced disruption of microfilaments during a critical interval in 1-cell C. elegans embryos alters the partitioning of developmental instructions to the 2-cell embryo. AB - We are investigating the involvement of the microfilament cytoskeleton in the development of early Caenorhabditis elegans embryos. We previously reported that several cytoplasmic movements in the zygote require that the microfilament cytoskeleton remain intact during a narrow time interval approximately three quarters of the way through the first cell cycle. In this study, we analyze the developmental consequences of brief, cytochalasin D-induced microfilament disruption during the 1-cell stage. Our results indicate that during the first cell cycle microfilaments are important only during the critical time interval for the 2-cell embryo to undergo the correct pattern of subsequent divisions and to initiate the differentiation of at least 4 tissue types. Disruption of microfilaments during the critical interval results in aberrant division and P granule segregation patterns, generating some embryos that we classify as 'reverse polarity', 'anterior duplication', and 'posterior duplication' embryos. These altered patterns suggest that microfilament disruption during the critical interval leads to the incorrect distribution of developmental instructions responsible for early pattern formation. The strict correlation between unequal division, unequal germ-granule partitioning, and the generation of daughter cells with different cell cycle periods observed in these embryos suggests that the three processes are coupled. We hypothesize that (1) an 'asymmetry determinant', normally located at the posterior end of the zygote, governs asymmetric cell division, germ-granule segregation, and the segregation of cell cycle timing elements during the first cell cycle, and (2) the integrity or placement of this asymmetry determinant is sensitive to microfilament disruption during the critical time interval. PMID- 2190788 TI - Retinoic acid-induced spina bifida: evidence for a pathogenetic mechanism. AB - Treatment of C57Bl/6J mice with three successive doses of all-trans retinoic acid (28 mg kg-1 body weight) on 8 day, 6 h (8d,6h), 8d,12h, and 8d,18h of gestation resulted in a high incidence (79%, 31/39 fetuses) of spina bifida with myeloschisis (spina bifida aperta) in near term fetuses. Twelve hours following the last maternal dose (9d,6h), the caudal aspects of treated embryos, were abnormal, with eversion of the neural plate at the posterior neuropore, as compared to its normal concavity in comparably staged control specimens. This eversion persisted in affected embryos through the time that the posterior neuropore should normally close. The distribution of cell death in control and experimental embryos was determined using vital staining with Nile blue sulphate and with routine histological techniques. Twelve hours following the maternal dosing regimen, experimental embryos showed evidence of excessive cell death, predominantly in the mesenchyme associated with the primitive streak and in the endoderm of the tail gut, both of which are readily identifiable sites of physiological cell death at this stage of development. In addition, the presumptive trunk neural crest cells located in the dorsal midline, cranial to the posterior neuropore, exhibited a marked amount of cell death in the experimental embryos. We propose that the major factor in the generation of spina bifida in this model is excessive cell death in the tail gut and mesenchyme ventral to the neuroepithelium of the posterior neuropore.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190789 TI - Developmental patterning of the carbohydrate antigen FC10.2 during early embryogenesis in the chick. AB - An oligosaccharide antigen (FC10.2), formerly described only in mammalian cells and secreted glycoproteins, has been detected and found to display striking temporal and spatial patterning in the chick during early embryonic development. This antigen is expressed on type 1 chains, which are isomers of oligosaccharides of the poly-N-acetyllactosamine series (type 2 chains). Immunoreactivities before and after neuraminidase treatment of serial sections of chick embryos during the first 17 stages of development indicate that the FC10.2 structure occurs predominantly in the sialylated form (S-FC10.2). The FC10.2 and S-FC10.2 antigens are prominent markers of the primordial germ cells, being strongly expressed by these cells from the pre-primitive streak stage onwards. S-FC10.2 is also a clear marker of the pronephric duct from its first appearance. Initially present over the entire apical surface of the ectoderm, antigenicity diminishes in an antero posterior direction as neurulation proceeds. A unique pattern for a carbohydrate antigen is displayed by cells of the primitive streak; antigenicity is lost with de-epithelialisation and ingression, but is regained in a pericellular distribution on the mesoderm cells that emerge from the primitive streak. Thereafter, successive changes in expression and distribution of FC10.2 and S FC10.2 are features of mesodermal tissues, particularly during somitogenesis. These antigens are prominent components of the extracellular matrix around the notochord and sclerotome cells. They are also prominent posteriorly in the subectodermal region, ceasing abruptly at the lateral limits of the embryo proper. Although no absolute correlations can yet be made, several features of the distribution of these antigens suggest that they may be integral components of, or ligands for, cell adhesion molecules. PMID- 2190790 TI - The spatiotemporal distribution of N-CAM in the retinotectal pathway of adult goldfish detected by the monoclonal antibody D3. AB - The spatiotemporal distribution of neural cell adhesion molecule (N-CAM) in the retinotectal system of adult goldfish was assessed by immunofluorescence using the monoclonal antibody (Mab) D3 against chick N-CAM. In immunoblots with extracts of cell surface membranes of fish brains, Mab D3 recognized a prominent band at 170K and a weak band at 130K (K = 10(3) Mr). N-CAM immunofluorescence on cells was restricted to the marginal growth zones of the retina and the tectum and, in normal fish, to the youngest axons from the new ganglion cells of the peripheral retinal margin. In fish with previously transected optic nerves (ONS), Mab D3 staining was found transiently on all axons from the site of the cut into the retinorecipient layers of the tectum, but disappeared from these axons 450 days after ONS. Growing retinal axons in vitro exhibited N-CAM immunofluorescence throughout their entire extent, including their growth cones. Glial cells cultured from regenerating optic nerves were, however, unlabeled. These data are consistent with the idea that N-CAM is involved in adhesive interactions of growing axons. The temporally regulated expression of N-CAM on the new retinal axons may contribute to the creation of the age-related organization of the axons in the retinotectal pathway of fish. PMID- 2190791 TI - Pharmacological treatment of patients with schizophrenia. Past and present problems and potential future therapy. PMID- 2190792 TI - Antineoplastic drugs in 1990. A review (Part I). AB - The drugs used to treat cancer today are a confusing array of compounds with differing origins, mechanisms of action, antitumour spectra, and toxicities. There are 5 chemically distinct types of alkylating agents; the prototypical agent is chlormethine (mustine) and the most recent addition is ifosfamide. Generally these drugs all work in the same fashion and their activity is cell cycle proliferation-dependent but phase-nonspecific. The antimetabolites consist of methotrexate, the pyrimidine and purine analogues, and pentostatin, an adenosine deaminase inhibitor and relative newcomer to the class. The individual mechanisms of action of these agents differ but cytotoxicity is generally cell cycle phase-specific. Naturally occurring antineoplastic agents include the vinca alkaloids, the antitumour antibiotics, 1-asparaginase, the epipodophyllotoxins, and homoharringtonine; it is the most diverse collection of compounds. For these drugs as well as the antimetabolites, the therapeutic and toxic effects often depend heavily on duration of exposure to the drug, an effect known as schedule dependency. Finally, the agents that do not fit one of the above categories are cisplatin (cis-platinum II) and its analogue carboplatin (which is being actively investigated), hydroxycarbamide (hydroxyurea), procarbazine, hexamethylmelamine, amsacrine, and mitoxantrone (mitozantrone). In the future we can expect not only the emergence of new antineoplastic drugs, but also further refinements in the use of existing drugs. We are beginning to understand the various types of resistance manifested by tumour cells. Our ability to use these potent and highly toxic agents safely should continue to improve. PMID- 2190793 TI - Endometriosis 1990. Current treatment approaches. AB - Endometriosis is an extremely common gynaecological disease, affecting between 1 and 5% of women of reproductive age. Women with endometriosis typically present for medical care with one of more of the following problems: pelvic pain, infertility, or a large adnexal mass (an endometrioma). The primary treatment for an endometrioma is surgical. However, long term postoperative hormone therapy may be necessary to prevent new endometriomas from developing. There is no evidence that hormonal therapy of endometriosis will improve fecundability in women with endometriosis and infertility. Pelvic pain due to endometriosis can be successfully treated with hormonal agents in the majority of patients. Four basic hormonal regimens are currently available for the treatment of endometriosis: (a) danazol; (b) gonadotrophin-releasing hormone (GnRH) [luteinising hormone releasing hormone (LHRH); gonadorelin] agonists; (c) progesterones (progestins); and (d) combined estrogens and progesterones. Randomised, controlled, clinical trials suggest that danazol and the GnRH agonists are equally effective in the treatment of endometriosis. However, the side effects caused by danazol and the GnRH agonists are markedly different. Danazol produces androgenic side effects including weight gain, hirsutism, acne, oily skin and deepening of the voice. GnRH agonists produce side effects due to hypoestrogenism, including hot flushes, osteoporosis and dry vagina. The ideal drug regimen for the treatment of endometriosis remains to be developed. PMID- 2190794 TI - Optimum therapy for acute pelvic inflammatory disease. AB - Neisseria gonorrhoeae is responsible for about one-third to one-half of cases of acute pelvic inflammatory disease (PID), although there is considerable geographical variation. Chlamydia trachomatis is also an important aetiological agent, and is currently isolated 4 times more commonly from the cervix than the gonococcus. However, it is now clear that acute PID is polymicrobial in aetiology. Even when N. gonorrhoeae and/or C. trachomatis are isolated from the endocervix, anaerobes such as Bacteroides fragilis, Peptococcus and Peptostreptococcus and aerobes, especially the Enterobacteriaceae such as E. coli, are also frequently isolated. Bacterial synergism, coinfection with the gonococcus and C. trachomatis and the involvement of multiple other micro organisms including aerobes and anaerobes and antibiotic resistance make the selection of an optimal antibiotic regimen difficult. The Centers for Disease Control (CDC) recommendations first proposed in 1982 and revised in 1985 emphasise broad spectrum antimicrobial therapy including coverage of C. trachomatis. In September 1989, the CDC revised its recommendation for the treatment of acute PID. Current recommendations include the use of newer third generation cephalosporins such as ceftriaxone, ceftizoxime and cefotaxime which give excellent coverage of the gonococcus and the Enterobacteriaceae. It is still important to include doxycycline or a tetracycline to cover C. trachomatis. For patients with advanced disease or a tubo-ovarian abscess, clindamycin plus gentamicin has been the regimen of choice. Aztreonam, a new monobactam, has several advantages over gentamicin including less toxicity, more dependable blood levels and good coverage of N. gonorrhoeae and the Enterobacteriaceae. PMID- 2190795 TI - Bendazac lysine. A review of its pharmacological properties and therapeutic potential in the management of cataracts. AB - Bendazac is an oxyacetic acid with anti-inflammatory, antinecrotic, choleretic and antilipidaemic properties, but its principal effect is to inhibit the denaturation of proteins. The lysine salt, which is better absorbed than the parent compound after oral administration, has been evaluated as a treatment for cataract, a condition which appears to result mainly from the denaturation, aggregation and precipitation of proteins within the lens. Results from a very small number of preliminary studies using objective photographic and densitometric methods have suggested that oral bendazac lysine, usually at a dosage of 500 mg 3 times daily, can stabilise the progression of lens opacification in patients with cataract. Significant improvements in individual and mean visual acuities in treated patients have been reported by several studies, but this parameter is not universally accepted as a reliable index of lens status. Preliminary studies evaluating bendazac lysine 0.5% eyedrops have reported comparable results to those obtained with oral treatment. Overall, tolerability of the drug has been good in studies to date. A dose-related laxative effect and other gastrointestinal disturbances are the most common adverse effects associated with oral therapy, and a transient burning sensation is the most commonly reported symptom occurring with eyedrop application. Bendazac lysine is one of a number of agents which have been introduced for the management of cataract. Although the results of preliminary studies have suggested that the drug may be useful for delaying the progression of cataract, further clinical studies using proven objective methods are required to fully establish its value in the management of this condition and its long term tolerability. PMID- 2190796 TI - Integrating perceptual and instrumental procedures in the assessment of velopharyngeal insufficiency. AB - Although technology for the instrumental assessment of velopharyngeal function has advanced, management decisions still too often depend only on subjective perceptual analyses. Both perceptual and instrumental appraisal are necessary for adequate assessment. Instrumental assessment is essential prior to surgical or other long-term management. The assessment is only as valid as the instruments used. If such instruments are not readily available, clinicians should refer patients to centers where they are available and these examinations are routinely performed. PMID- 2190797 TI - Epidemiology of nasopharyngeal carcinoma. PMID- 2190798 TI - Insulin-like growth factor-I and -II messenger RNA expression in muscle, heart, and liver of streptozotocin-diabetic swine. AB - We have investigated the effects of streptozotocin-diabetes and fasting in juvenile swine by monitoring IGF-I and -II gene expression in muscle, heart, and liver tissues. In diabetic pigs, IGF-I messenger RNAs (mRNA) were decreased by 50% in muscle and liver tissues, and by 70% in heart. The imposition of fasting on diabetic animals tended to further decrease IGF-I mRNA levels, and fasting alone also decreased IGF-I mRNA abundance in the three tissues (P less than 0.05). Insulin therapy restored IGF-I mRNA levels to normal in muscle and livers but was less effective in hearts of diabetic pigs. Relative IGF-I mRNA expression in heart and muscle tissues was 2-fold and 4-fold higher, respectively, than in liver tissues under normal conditions in these animals. Serum IGF-I concentrations and tissue extractable immunoreactive IGF-I levels were also measured. Serum IGF-I was markedly decreased in the diabetic state, dropping to 70% below control levels (P less than 0.01). Extractable IGF-I in liver declined by 50% with diabetes (P less than 0.01), and by 30% in muscle with diabetes and fasting (P less than 0.05), but no significant changes in heart levels of IGF-I protein were detected. Expression levels of IGF-II mRNAs in the three tissues were unaffected by diabetes or fasting. These results are consistent with earlier observations in rat liver and further demonstrate that IGF-I expression in muscle and heart is altered by diabetes and fasting, whereas IGF-II mRNAs do not change. PMID- 2190799 TI - Developmental regulation of murine mammary progesterone receptor gene expression. AB - Previously we have shown that in normal murine mammary glands progesterone receptor (PgR) levels are modulated as a function of development and differentiation such that lactating mammary glands do not contain detectable levels of PgR as measured by steroid binding. The objective of the present study was to determine whether the lack of steroid binding in lactating mammary glands was due to the absence of receptor protein and if so whether it was accompanied by an alternation in the pattern of PgR gene expression. Accordingly, we have performed an immunological analysis of murine mammary PgR isolated from different developmental states and have also examined these tissues for PgR gene expression. In mammary tissues from all developmental states other than lactation, immunoreactive PgR corresponding to both A and B forms of the protein were detected. Analysis for PgR mRNA revealed multiple species in mammary tissues and the relative order of abundance of the various transcripts and their sizes were approximately 6.9 greater than 8.7 greater than 3.5 greater than 2.7 greater than 4.2. The 6.9 and 8.7 kilobase transcripts accounted for between 70-80% of total mRNA. All five species of mRNA were detected in tissues from nulliparous mice which decreased dramatically during pregnancy, became undetectable during lactation, and were once again detectable in tissues from mice undergoing lactational involution. Experiments designed specifically to examine the effect of estradiol on mammary PgR mRNA revealed that in contrast to tissues from other developmental states, lactating mammary glands were unable to respond to estradiol with an increase in PgR mRNA. Based on these findings and the fact that estrogenic insensitivity of lactating mammary glands coexists with the presence of ER we propose that in this tissue there is an alteration in the estrogen dependent transcriptional regulation of PgR gene expression. PMID- 2190800 TI - Characterization and purification of a secreted plasminogen activator inhibitor (PAI-1) induced by transforming growth factor-beta 1 in normal rat kidney (NRK) cells: decreased PAI-1 expression in transformed NRK cells. AB - Type 1 transforming growth factor-beta (TGF beta 1) was found to be a potent inducer of the secretion of a 49,000 mol wt protein by normal rat kidney (NRK) cells. This protein was related to type 1 plasminogen activator inhibitor (PAI-1) on the basis of molecular mass, activity in the presence of sodium dodecyl sulfate, immunoprecipitation by antibodies to PAI-1, and N-terminal sequence analysis. PAI-1 levels in the conditioned medium of NRK cells were increased 5- to 11-fold when cells were incubated with picomolar concentrations of TGF beta 1 for 24 h, reaching a concentration of approximately 0.3 microgram/ml. The secreted PAI-1 was deposited in the NRK extracellular matrix as well as released into the culture medium. A spontaneously transformed NRK cell line was found to secrete 3-4 times less PAI-1, in the absence or presence of TGF beta 1, compared to the parent cell line, while PAI-1 secretion in Kirsten sarcoma virus transformed NRK cells was almost completely abrogated. A novel purification procedure was established, which results in the isolation of highly active and detergent-free TGF beta 1-induced PAI-1. PMID- 2190801 TI - Vitamin D depletion retards the normal regeneration process after partial hepatectomy in the rat. AB - 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], the hormone of the vitamin D3 (D3) endocrine system, has been shown to influence malignant and normal cell proliferation/differentiation, while insulin (I) is known to be essential for liver growth. To investigate the influence of D3 on liver regeneration, the effect of the D status was studied in D-depleted rats (D-) pretreated with: G1, placebo (D-, hypocalcemic); G2, oral calcium only (D-, normocalcemic); G3, D3; and G4, 1,25-(OH)2D3. Two thirds hepatectomy (HX) or sham operation was performed, and regeneration was studied for 3 weeks. I response to glucose challenge and the hepatic I receptor were also studied. Cell volume, DNA, and RNA were not affected by pretreatment. After HX, the pattern of [3H]thymidine incorporation into DNA (P less than 0.003) and the cell labeling index (P less than 0.0001) were highly influenced by pretreatment and suggestive of an earlier appearance of the S phase of the cell cycle in the 1,25-(OH)2D3-treated compared to the D- hypocalcemic group. Furthermore, the mitotic index revealed a significant effect of pretreatment (P less than 0.01), with peak mitosis 24 h after HX in D3-treated and 1,25-(OH)2D3-treated rats compared to 30-36 h after HX in the D- groups. Liver weight restitution was impaired in D- rats (P less than 0.009) and is illustrated by the estimated time required to achieve 70% recovery of the resected liver mass, which was found to be 186 and 300 h in G1 and G2, and 154 and 107 h in G3 and G4. G1 rats had significantly higher glucose concentrations (fasting as well as after glucose injection) and reduced I secretion when challenged with glucose (P less than 0.001); they also had an upregulation in hepatic I receptor number (P less than 0.005) compared to calcium or D3-treated rats, while 1,25-(OH)2D3 led to a liver I receptor number similar to that found in hypocalcemic D- rats; the affinity of the I receptor was, however, only slightly changed by pretreatment (P less than 0.08). Our data indicate that in D depletion, hypocalcemia retards DNA synthesis and liver mass recovery, while normocalcemia contributes to DNA synthesis, but fails to sustain mitosis and compensatory liver growth to a level comparable to that found after D3 and/or 1,25-(OH)2D3 repletion. The observation that both D3 and 1,25-(OH)2D3 significantly promoted normal liver recovery after partial HX illustrates the role of the D endocrine system in normal cell physiology in vivo. PMID- 2190802 TI - Gonadotropin-releasing hormone-stimulated luteinizing hormone secretion by perifused pituitary cells from normal, gonadectomized, and testicular feminized rats. AB - To elucidate further the manner in which gonadal steroids influence the secretion of LH, we examined the effects of gonadectomy and the absence of functional androgen receptors on GnRH-induced LH release from dispersed rat anterior pituitary cells. Intact and gonadectomized (GNX) normal rats and androgen resistant, testicular feminized (Tfm) animals from the King x Holtzman strain (a mutant strain that possesses defective androgen receptors) were used. Dispersed pituitary cells were perifused with Medium 199 during a 4-h equilibration period and then subjected to eight 2.5-min pulses of GnRH introduced at 30-min intervals at concentrations ranging from 0.03-100 nM. Basal LH secretion by cells from intact male and female rats was indistinguishable (P = 0.79) and was substantially lower (P less than 0.0001) than that by cells from GNX male and female animals. Basal LH secretion by cells from Tfm rats was significantly higher (P less than 0.01) than that by cells from intact animals, but lower (P less than 0.005) than that by cells from GNX animals. In response to GnRH, perifused pituitary cells from animals representing all experimental groups demonstrated concentration-dependent LH release. Pituitary cells from intact female rats showed an overall greater (P less than 0.05) response to GnRH than cells from intact male rats. Pituitary cells from Tfm rats demonstrated a greater GnRH-stimulated LH mean response than cells from intact male (P less than 0.0001) or intact female (P less than 0.0001) rats. Gonadectomy of male rats resulted in an overall GnRH-stimulated LH release similar to that exhibited by cells from gonadectomized female rats (P = 0.61). Cells from Tfm animals released more LH in response to GnRH than those from gonadectomized male and female rats (P less than 0.001). These data demonstrate that the release of LH in response to GnRH by pituitary cells from intact male rats (i.e. in the presence of androgen and functional androgen receptors) is less than that seen by cells from intact females rats. Since circulating levels of testosterone and estradiol are known to be elevated in the testicular feminized rat, the heightened GnRH-stimulated LH release by cells from such animals may reflect either the long term lack of androgenic influence and/or the combined effects of androgen resistance and elevated levels of circulating estrogens. PMID- 2190803 TI - Intrinsic pituitary interleukin-1 beta is induced by bacterial lipopolysaccharide. AB - Using a specific antiserum recognizing recombinant rat interleukin-1 beta (IL-1 beta), immunoreactive material was localized to cytoplasmic granules in anterior pituitary endocrine cells and colocalized with TSH in thyrotropes. Authenticity was established by Northern blot hybridization using a specific rat IL-1 beta cRNA probe, revealing a 1.8-kilobase mRNA identical to that in the spleen. The marked increase in anterior pituitary IL-1 beta message after the administration of bacterial lipopolysaccharide, raises the possibility that IL-1 beta may be involved in paracrine or autocrine regulation of pituitary function during infectious challenge. PMID- 2190804 TI - The role of calcium ions in toxic cell injury. AB - Calcium ions have been increasingly implicated as a mediator of the mechanisms generating lethal cell injury under a variety of pathologic circumstances. An overview of the various roles suggested for such alterations in cellular calcium homeostasis is presented. The central role of plasma membrane damage in the genesis of irreversible cell injury is used to divide the postulated roles for calcium ions into two major mechanisms. On the one hand, calcium ions have been proposed as mediators of the functional consequences of plasma membrane injury. An influx of extracellular calcium ions across a damaged permeability barrier and down a steep concentration gradient may convert potentially reversible injury into irreversible injury. On the other hand, alterations in intracellular calcium homeostasis are postulated to participate in the mechanisms generating potentially lethal plasma membrane injury. The release of calcium stores sequestered within intracellular organelles raises the cytosolic concentration of free calcium, a process that may activate, in turn, a number of membrane disruptive processes. The data supporting these two distinct actions of calcium are reviewed and discussed. PMID- 2190805 TI - Extracellular calcium effects on cell viability and thiol homeostasis. AB - Studies of chemically induced cell injury and death, which have used as model systems freshly isolated rat hepatocytes and hepatocytes in culture, are discussed. An important model uses the omission of Ca2+ from the medium during rat hepatocyte incubations. Ca2+ omission induces an intense oxidative stress within hepatocytes incubated in a 95% O2 + 5% CO2 atmosphere. The relationship of calcium homeostasis to the parameters of oxidative stress is important to understanding the progression from reversible to irreversible injury. In the Ca2+ omission model, the vitamin E (Vit. E) content of hepatocytes is important for the prevention of cell injury. Recent studies with rat hepatocytes show that ruthenium red (RR) and La3+, which block Ca2+ translocation through the mitochondrial uniport, can prevent malondialdehyde (MDA) formation, reduced glutathione (GSH), and protein-SH loss, Vit. E loss, and LDH leakage induced by Ca2+ omission from the incubation medium. Ca2+ omission promoted a marked loss of mitochondrial transmembrane potential (delta phi) that was prevented by RR, EGTA, Vit. E, and desferrioxamine. The absence of extracellular Ca2+ may cause mitochondrial Ca2+ cycling that contributes to the observed oxidative stress, resultant loss of cell viability, and protein thiol homeostasis. Chemical agents including a glutathione-depleting agent, ethacrynic acid, and a redox cycling agent, adriamycin, increase the loss of cell viability caused by a Ca2(+)-free medium, but they have some additional effects on cellular processes. The demise of cell viability by the agent is also preventable by Vit. E supplementation. Ca2+ has a role in cell injury that appears to uniquely involve mitochondrial homeostasis. PMID- 2190807 TI - Regulation of renal sodium calcium exchange by PTH: alteration with age. AB - Parathyroid hormone, when incubated with renal cells acting in vivo and in vitro, increased Na+/Ca2+ exchange activity. The effect of parathyroid hormone was specific for biologically active analogs and could be mimicked by cAMP and forskolin. Parathyroid hormone-sensitive Na+/Ca2+ exchange activity was markedly blunted in cells from senescent rats. Parathyroid hormone-stimulated adenylate cyclase was also decreased in aging. In contrast, forskolin-stimulated Na(+) dependent Ca2+ efflux and adenylate cyclase did not change with senescence. Decrease of PTH binding sites was observed in cells from old rats. Further, cells from 24-month-old rats had decreased Gs and Gi proteins, as detected by ADP ribosylation. Since serum iPTH level was elevated in the old rat and could contribute to the desensitization to PTH, we tested this hypothesis by comparing sham-operated and PTX animals. The decreases in PTH-sensitive Na+/Ca2+ exchange activity and adenylate cyclase activity in cells from 24-month-old rats could be completely negated by parathyroidectomy. Decrease in PTH binding sites and contents of Gs and Gi in cells from aged-rats was partially negated by the surgery. In conclusion, our results suggested that the age related blunting in responses of renal cells to PTH was due, at least in part, to the elevated serum iPTH level in old rats. PMID- 2190809 TI - Impact of halogenated compounds on calcium homeostasis in hepatocytes. AB - Halocarbons (CCl4, 1,1-dichlorethylene) cause a wide spectrum of effects and injury in hepatocytes. One early effect of these compounds is the inhibition and destruction of the endoplasmic reticulum (ER) calcium pump. Subsequent to inhibition of this pump, the ER calcium pool is depleted and cytosolic levels of calcium are increased for a prolonged period of time. This effect of halocarbons has been characterized and is similar in vivo and in vitro. The importance of this redistribution of cell calcium in expression of halocarbon injury of hepatocytes has not been fully resolved. Several degradative enzymes (phospholipases, proteases) have been implicated as calcium-dependent mediators in toxicity. Our preliminary studies of the effect of calcium redistribution suggest that activation of a calcium-sensitive endonuclease in liver does not play a central role in initiating the lethal effect of halocarbons on hepatocytes. PMID- 2190808 TI - Inositol phosphate formation and its relationship to calcium signaling. AB - The activation of a variety of cell surface receptors results in a biphasic increase in the cytoplasmic Ca2+ concentration due to the release or mobilization of Ca2+ from intracellular stores and to the entry of Ca2+ from the extracellular space. It is well established that phosphatidylinositol 4,5-bisphosphate hydrolysis is responsible for the changes in Ca2+ homeostasis. Stimulation of Ca2(+)-mobilizing receptors also results in the phospholipase C-catalyzed hydrolysis of the minor plasma membrane phospholipid, phosphatidylinositol 4,5 bisphosphate, with the concomitant formation of inositol (1,4,5) trisphosphate [1,4,5)IP3) and diacylglycerol. Analogous to the adenylyl cyclase signaling system, receptor-mediated stimulation of phospholipase C also appears to be mediated by one or more intermediary guanine nucleotide-dependent regulatory proteins. There is strong evidence that (1,4,5)IP3 stimulates Ca2+ release from intracellular stores. The Ca2(+)-releasing actions of (1,4,5)IP3 are terminated by its metabolism through two distinct pathways. (1,4,5)IP3 is dephosphorylated by a 5-phosphatase to inositol (1,4) bisphosphate; alternatively, (1,4,5)IP3 can be phosphorylated to inositol (1,3,4,5) tetrakisphosphate by a 3-kinase. Whereas the mechanism of Ca2+ mobilization is understood, the precise mechanisms involved in Ca2+ entry are not known. A recent proposal that (1,4,5)IP3 secondarily elicits Ca2+ entry by emptying an intracellular Ca2+ pool will be considered. This review summarizes our current understanding of the mechanisms by which inositol phosphates regulate cytoplasmic Ca2+ concentrations. PMID- 2190806 TI - Signal transduction mechanisms involved in hormonal Ca2+ fluxes. AB - This article reviews literature up to mid-1988 covering recent developments pertaining to agonist-induced Ca2+ signaling in various cell types. A large amount of experimental evidence supports a mechanism involving specific guanine nucleotide-binding proteins (G-proteins) as transducing factors between occupancy of a wide variety of receptors by many different agonists and activation of polyphosphoinositide specific phospholipase C enzymes. Although many different G proteins and phospholipase C enzymes have been purified and cloned, successful reconstitution of the components has not been achieved. Hence, many questions concerning the specificity of coupling between particular receptors to a particular G-protein and phospholipase C subtype remain unresolved. Phospholipase C subtypes isolated from the membrane and soluble fractions of the cell are directly activated by Ca2+ and, preferentially, hydrolyse phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 4-phosphate (PIP). The role of the G-protein is to stimulate inositol lipid breakdown at free Ca2+ concentrations (0.1-0.2 microM) typical of unstimulated cells. Overwhelming evidence supports the concept that Ins 1,4,5-P3, the product of PIP2 hydrolysis, is responsible for the initial agonist-induced Ca2+ transient by mobilization of Ca2+ from a specialized intracellular store. An Ins 1,4,5-P3 receptor has been purified that may correspond to the postulated Ins 1,4,5-P3 gated Ca2+ channel. Despite a growing understanding of the complexities of the metabolism of Ins 1,4,5-P3 and a successful purification of many enzymes involved, including the ATP-dependent 3-kinase that converts Ins 1,4,5-P3 to Ins 1,3,4,5-P4, the role of Ins 1,3,4,5-P4 as a putative second messenger remains enigmatic. Multiple forms of protein kinase C have been described and the role is well established for a 1,2-diacylglycerol, the second product of PIP2 hydrolysis, as its physiological activator. Although protein kinase C has been shown to phosphorylate and modulate the activity of several proteins involved in the Ca2+ signaling pathway and Ca2+ transport, the physiological significance of the protein kinase C in agonist stimulated cell function requires further elucidation. The extension of measurements of hormone-induced Ca2+ changes to single cells has shown that the occurrence of Ca2+ oscillations is a common phenomena. Elucidation of the biochemical mechanisms causing this oscillatory response and its physiological significance represents an important challenge for future studies. PMID- 2190810 TI - Calcium in renal cells. Modulation of calcium-dependent activation of phospholipase A2. AB - Calcium has been implicated as a regulatory factor in many physiological and pathophysiological processes in the renal cell. Under physiological conditions, the cytosolic free calcium concentration is maintained at approximately 100 nM. Most of the releasable cell Ca2+ resides in the nonmitochondrial compartments. In addition to the plasma membrane Ca2+ transport processes, there is a high affinity, low-capacity buffering capability of nonmitochondrial organelles and a lower-affinity high-capacity mitochondrial Ca2+ buffering capability. A critical enzymatic effector of Ca2+ action in the cell is phospholipase A2. By using digitonin-permeabilized renal mesangial cells, the [Ca2+] dependency of phospholipase A2 was characterized. The [Ca2+] sensitivity was insufficient to explain the phospholipase A2 activation observed with vasopressin. In both intact cells, as well as permeabilized cells, it was found that protein kinase C activation markedly enhanced the Ca2+ calmodulin-dependent activation of phospholipase A2. In response to platelet-derived growth factor, it was found that arachidonic acid release preceded phospholipase C activation. This suggests that other effectors besides Ca2+ and protein kinase C may also be important for phospholipase A2 activation. In an experimental model designed to mimic postischemic reperfusion damage to renal mitochondria, it was demonstrated that reactive oxygen species act synergistically with Ca2+ to activate mitochondrial phospholipase A2, which mediates damage to site I of the electron transport chain, the F1F0 ATPase, and the adenine nucleotide translocase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190811 TI - Calcium ion as intracellular messenger and cellular toxin. AB - Ca2+ serves a nearly universal intracellular messenger function in cell activation, but excess Ca2+ is also a cellular toxin. The possibility of Ca2+ intoxication is minimized by an elaborate autoregulatory system in which changes in Ca2+ influx rate across the plasma membrane are rapidly compensated for by parallel changes in Ca2+ efflux rate. By this mean, cellular Ca2+ homestasis is maintained so that minimal changes in total cell calcium and cytosolic Ca2+ concentration occur during sustained Ca2(+)-mediated responses. Rather than a sustained increase in cytosolic Ca2+ concentration, it is the localized cycling of Ca2+ across the plasma membrane that is the critically important Ca2+ messenger during the sustained phase of cellular responses mediated via surface receptors linked to the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2). PIP2 hydrolysis gives rise to inositol(1,4,5)trisphosphate (IP3) and diacylglycerol (DAG). The IP3 acts to release Ca2+ from an intracellular pool, thereby causing a transient rise in cytosolic Ca2+ concentration. This transient Ca2+ signal activates calmodulin-dependent protein kinases transiently, and hence, causes the transient phosphorylation of a subset of cellular proteins that mediate the initial phase of the response. The DAG brings about the association of protein kinase C (PKC) with the plasma membrane where a receptor-mediated increase in Ca2+ cycling across the membrane regulates PKC activity. The sustained phosphorylation of a second subset of proteins by PKC mediates the sustained phase of the response. Hence, Ca2+ serves as a messenger during both phases of the cellular response, but its cellular sites of action, its mechanisms of generation, and its molecular targets differ during the initial and sustained phases of the response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190812 TI - Cotinine analytical workshop report: consideration of analytical methods for determining cotinine in human body fluids as a measure of passive exposure to tobacco smoke. AB - A two-day technical workshop was convened November 10-11, 1986, to discuss analytical approaches for determining trace amounts of cotinine in human body fluids resulting from passive exposure to environmental tobacco smoke (ETS). The workshop, jointly sponsored by the U.S. Environmental Protection Agency and Centers for Disease Control, was attended by scientists with expertise in cotinine analytical methodology and/or conduct of human monitoring studies related to ETS. The workshop format included technical presentations, separate panel discussions on chromatography and immunoassay analytical approaches, and group discussions related to the quality assurance/quality control aspects of future monitoring programs. This report presents a consensus of opinion on general issues before the workshop panel participants and also a detailed comparison of several analytical approaches being used by the various represented laboratories. The salient features of the chromatography and immunoassay analytical methods are discussed separately. PMID- 2190813 TI - The relationship between mutagenicity and chemical composition of polycyclic aromatic compounds from coal pyrolysis. AB - The polycyclic aromatic compounds (PAC) produced from the pyrolysis of a bituminous coal at temperatures of 1125 to 1425 degrees K prove to be mutagenic to S. typhimurium, both in the presence and in the absence of postmitochondrial supernatant (PMS) prepared from Aroclor 1254-induced rat liver. Mutagenicity of the PAC samples measured in the absence of PMS exhibits little dependence on pyrolysis temperature; that measured in its presence is higher at the higher pyrolysis temperatures. However, because of the decrease in PAC yield as the temperature is raised, mutagenicity per mass of coal consumed falls with an increase in temperature if measured without PMS (-PMS) and peaks at an intermediate temperature of 1378 degrees K if measured with PMS (+PMS). Using a new chromatographic technique, we have split each coal-derived PAC sample into two fractions: LC1, containing PAC with alkyl and O-containing substitutions and LC2, consisting of unsubstituted PAC. Substituted (LC1) fractions show no significant +PMS mutagenicity, indicating that, as a whole, the alkylated PAC in our coal pyrolysis products are not mutagenic. Only at the higher temperatures do the substituted fractions exhibit significant -PMS mutagenicity, attributed to PAC with carbonyl or etheric functionalities. The extremely low yields of the substituted PAC under the conditions where they show some activity, however, ensure that they contribute little to overall mutagenicity. In contrast to the substituted fractions, the unsubstituted (LC2) fractions display significant mutagenicity under all conditions and appear to be responsible for virtually all of the mutagenicity in these coal-derived PAC samples. In this fraction, -PMS activity is attributed to nitrogen-containing heterocyclic aromatics. PMID- 2190814 TI - A health-based approach for sampling shallow soils at hazardous waste sites using the AALsoil contact criterion. AB - Strategies for sampling shallow soils at hazardous waste sites are employed primarily to evaluate levels and distributions of contamination. The ensuing analyses of potential public health impacts are therefore dependent on the sampling design rather than having the sampling design based on the data needs for evaluating potential public health impacts of shallow soil contamination. We define a specific objective that guides the sampling of shallow soils. The sampling results can thereby be directly employed to evaluate potential public health impacts from direct contact exposures to shallow soil contamination. PMID- 2190815 TI - Hormonal regulation of cytosolic free calcium and its functional consequences: the GH-cell model. AB - Use of clonal strains of prolactin (PRL)- and growth hormone-producing rat pituitary cells has proven informative in elucidating a number of the early biochemical, ionic, and secretory events regulated by the hypothalamic tripeptide, thyrotropin-releasing hormone (TRH). TRH causes biphasic changes in the concentration of cytosolic free calcium [( Ca2+]i) in GH4C1 cells and biphasic changes in hormone secretion. Early changes occur on a msecond to second scale and late changes, on a time scale of minutes. Although increases in [Ca2+]i are essential for enhanced secretion, at least in the case of the rapid initial phase, the TRH-induced increase in [Ca2+]i is necessary, but not sufficient to enhance secretion. A co-mediator with calcium appears to be diacylglycerol. The majority of the calcium involved in the early phase of rise in [Ca2+]i induced by TRH is derived from intracellular sources, while essentially all of the calcium rise observed in the late phase is derived from extracellular calcium entering the cell through both voltage-dependent and voltage-independent conductances. Because TRH causes an elevation of inositol(1,4,5) trisphosphate [Ins(1,4,5)P3] within seconds, but not mseconds, further studies are required before it can be concluded unequivocally that Ins(1,4,5)P3 is the sole mediator of the rapid phase of rise in [Ca2+]i induced by TRH in GH-cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190816 TI - Effects of changes in calmodulin levels on cell proliferation. AB - Calmodulin (CaM) is one of several proteins regulated in a cell cycle-dependent manner. CaM is synthesized at the G1/S boundary and has been implicated in the regulation of cell cycle progression. To elucidate the role of calmodulin in cell cycle control, clonal mouse C127 cell lines transformed with one of four different bovine papilloma virus (BPV)-based vectors were studied. These vectors express a) a chicken CaM gene regulated by its own promoter (CM cells), b) the chicken CaM gene regulated by the inducible human metallothionein-IIa promoter (MCM cells), c) CaM antisense RNA using the Zn2+ inducible mouse metallothionein I (mMT-I) promoter (AS cells), or d) a rat parvalbumin gene using the chicken CaM promoter (PV cells). C127 cells transformed by BPV-1 alone (BPV cells) are used as a control in each case. Previous studies showed that a 4-fold increase in CaM levels in CM cells shortened the cell cycle by reducing the length of the G1 period. Expression of parvalbumin in PV cells has no effect on cell cycle length, suggesting that increased CAM, and not simply increased Ca2(+)-binding protein, accelerates proliferation. Zn2(+)-induced expression of the chicken CaM gene in MCM cells increased the rate of proliferation, while Zn2(+)-induced expression of high levels of CaM anti-sense RNA stops proliferation at Zn2+ levels that do not affect the growth of BPV cells. In CM cells increased CaM affects cell cycle dependent level of mRNAs for tubulin, vimentin, and c-myc relative to the levels in BPV cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190817 TI - Regulation of hormone-induced Ca2+ mobilization in the human platelets. AB - alpha-Thrombin, gamma-thrombin, and platelet-activating factor each stimulated the mobilization of intracellular Ca2+ stores in aspirin-treated human platelets. This was followed by desensitization of the receptors, as shown by the return of the Ca2+ level to basal values and by the fact that a subsequent addition of a second different agonist, but not the same agonist, could again elicit a response. Epinephrine, acting on alpha 2-adrenergic receptors, was by itself ineffective at mobilizing Ca2+ stores. However, when added after the thrombin induced response, epinephrine could evoke a considerable release of Ca2+ from cellular stores. This appeared to be due to epinephrine recoupling thrombin receptors to phospholipase C. In support of this, epinephrine was able to induce the formation of inositol triphosphate when added after the response to thrombin had also become desensitized. Alone, epinephrine was without effect. Pre activation of protein kinase C with the phorbol ester abolished these effects of epinephrine, suggesting that epinephrine was working by activating a protein which could be inactivated by phosphorylation. Our current work is to characterize this protein that may be a member of the Gi, GTP-binding protein family. PMID- 2190818 TI - An overview of techniques for the measurement of calcium distribution, calcium fluxes, and cytosolic free calcium in mammalian cells. AB - An array of techniques can be used to study cell calcium metabolism that comprises several calcium compartments and many types of transport systems such as ion channels, ATP-dependent pumps, and antiporters. The measurement of total cell calcium brings little information of value since 60 to 80% of total cell calcium is actually bound to the extracellular glycocalyx. Cell fractionation and differential centrifugation have been used to study intracellular Ca2+ compartmentalization, but the methods suffer from the possibility of Ca2+ loss or redistribution among cell fractions. Steady-state kinetic analyses of 45Ca uptake or desaturation curves have been used to study the distribution of Ca2+ among various kinetic pools in living cells and their rate of Ca2+ exchange, but the analyses are constrained by many limitations. Nonsteady-state tracer studies can provide information about rapid changes in calcium influx or efflux in and out of the cell. Zero-time kinetics of 45Ca uptake can detect instantaneous changes in calcium influx, while 45Ca fractional efflux ratio, can detect rapid stimulations or inhibitions of calcium efflux out of cells. Permeabilized cells have been successfully used to gauge the relative role of intracellular organelles in controlling [Ca2+]i. The measurement of the cytosolic ionized calcium ([Ca2+]i) is undoubtedly the most important and, physiologically, the most relevant method available. The choice of the appropriate calcium indicator, fluorescent, bioluminescent, metallochromic, or Ca2(+)-sensitive microelectrodes depends on the cell type and the magnitude and time constant of the event under study. Each probe has specific assets and drawbacks. The study of plasma membrane vesicles derived from baso-lateral or apical plasmalemma can also bring important information on the (Ca2(+)-Mg2+) ATPase-dependent calcium pump and on the kinetics and stoichiometry of the Na(+)-Ca2+ antiporter. The best strategy to study cell calcium metabolism is to use several different methods that focus on a specific problem from widely different angles. PMID- 2190819 TI - Calcium measurements with electron probe X-ray and electron energy loss analysis. AB - This paper presents a broad survey of the rationale for electron probe X-ray microanalysis (EPXMA) and the various methods for obtaining qualitative and quantitative information on the distribution and amount of elements, particularly calcium, in cryopreserved cells and tissues. Essential in an introductory consideration of microanalysis in biological cryosections is the physical basis for the instrumentation, fundamentals of X-ray spectrometry, and various analytical modes such as static probing and X-ray imaging. Some common artifacts are beam damage and contamination. Inherent pitfalls of energy dispersive X-ray systems include Si escape peaks, doublets, background, and detector calibration shifts. Quantitative calcium analysis of thin cryosections is carried out in real time using a multiple least squares fitting program on filtered X-ray spectra and normalizing the calcium peak to a portion of the continuum. Recent work includes the development of an X-ray imaging system where quantitative data can be retrieved off-line. The minimum detectable concentration of calcium in biological cryosections is approximately 300 mumole kg dry weight with a spatial resolution of approximately 100 A. The application of electron energy loss (EELS) techniques to the detection of calcium offers the potential for greater sensitivity and spatial resolution in measurement and imaging. Determination of mass thickness with EELS can facilitate accurate calculation of wet weight concentrations from frozen hydrated and freeze-dried specimens. Calcium has multiple effects on cell metabolism, membrane transport and permeability and, thus, on overall cell physiology or pathophysiology. Cells can be rapidly frozen for EPXMA during basal or altered functional conditions to delineate the location and amount of calcium within cells and the changes in location and concentration of cations or anions accompanying calcium redistribution. Recent experiments in our laboratory document that EPXMA in combination with other biochemical and electrophysiological techniques can be used to study, for example, sodium and calcium compartmentation in cultured cardiac cells. Such analyses can also be used to clarify the role of calcium in anoxic renal cell injury and to evaluate proposed ionic defects in cells of individuals with cystic fibrosis. PMID- 2190820 TI - The role of cell calcium in current approaches to toxicology. AB - All cells contain elaborate systems for the spatial and temporal regulation of the calcium ion, [Ca2+]i, and diverse Ca2+ receptor and biochemical response systems that are regulated by these changes in [Ca2+]i. Toxicants that perturb the mobilization or homeostasis of [Ca2+]i will place the regulation of these processes outside the normal range of physiological control. Many classes of chemical toxicants, including metals, solvents, and pesticides, may have particular aspects of cell calcium as key cellular and molecular targets of toxicant action. However, experimental proof of these targets as a specific site of toxicant action is challenging and technically difficult as a result of the complexity and diversity of these processes. To fully establish and understand the target role of the calcium messenger system in toxicant action, it is necessary to distinguish between the effects of a toxicant on (a) the calcium mobilization and homeostatic processes, (b) the calcium-mediated processes, and (c) from those processes which co-regulate or counter-regulate these calcium mediated processes. As our understanding of the calcium messenger system expands, these insights will be increasingly applied to understanding the mechanisms of action of toxic chemicals. PMID- 2190821 TI - Use of photoproteins as intracellular calcium indicators. AB - The calcium-regulated photoproteins, of which aequorin is the best known, continue to be one of the most useful groups of intracellular Ca2+ indicators. They are self-contained bioluminescent systems that emit blue light in the presence of Ca2+ ions, can readily be purified intact, and are nontoxic when introduced into foreign cells. They have been used successfully as Ca2+ indicators in almost every kind of cell, but are most widely used in muscle cells because of their relative freedom from motion artifacts. Photoproteins have also been used in conjunction with microscopic image intensification to localize Ca2+ in cells. Their large molecular size makes them difficult to introduce into cells, but once there, they have the advantage of staying in the cytoplasm. Aequorin can be microinjected satisfactorily into single cells of almost any size, but a number of alternative methods for introducing photoproteins into cells have been developed in recent years. Disadvantages of the photoproteins for some applications include the nonlinear relation between [Ca2+] and light intensity, the modest speed with which they respond to sudden changes in [Ca2+], and the fact the Mg2+ antagonizes the effect of Ca2+. Native photoproteins consist of a mixture of isospecies, and there are differences in Ca2+ sensitivity and in kinetic properties--both among photoproteins and among the isospecies of a given photoprotein. The genes for several of the isospecies of aequorin have been cloned and expressed in E. coli. It seems reasonable to hope that genetic engineering techniques may soon make it possible to consider using, as Ca2+ indicators, rare isospecies or rare photoproteins that have optimal properties for particular applications. PMID- 2190822 TI - Multiparameter digitized video microscopy of toxic and hypoxic injury in single cells. AB - There is no clear picture of the critical events that lead to the transition from reversible to irreversible injury. Many studies have suggested that a rise in cytosolic free Ca2+ initiates plasma membrane bleb formation and a sequence of events that lead ultimately to cell death. In recent studies, we have measured changes in cytosolic free Ca2+, mitochondrial membrane potential, cytosolic pH, and cell surface blebbing in relation to the onset of irreversible injury and cell death following anoxic and toxic injury to single hepatocytes by using multiparameter digitized video microscopy (MDVM). MDVM is an emerging new technology that permits single living cells to be labeled with multiple probes whose fluorescence is responsive to specific cellular parameters of interest. Fluorescence images specific for each probe are collected over time, digitized, and stored. Image analysis and processing then permits quantitation of the spatial distribution of the various parameters with the single living cells. Our results indicate the following: The formation of plasma membrane blebs accompanies all types of injury in hepatocytes. Cell death is a rapid event initiated by rupture of a plasma membrane bleb, and it is coincident with the onset of irreversible injury. An increase of cytosolic free Ca2+ is not the stimulus for bleb formation or the final common pathway leading to cell death. A decrease of mitochondrial membrane potential precedes the loss of cell viability. Cytosolic pH falls by more than 1 pH unit during chemical hypoxia. This acidosis protects against the onset of cell death. PMID- 2190823 TI - Number of deaths due to lung diseases: how large is the problem? PMID- 2190824 TI - Literature review on duckweed toxicity testing. AB - Duckweed commonly refers to a group of floating, flowering plants of the family Lemnaceae. Duckweed plants are fast growing and widely distributed. They are easy to culture and to test. Some reports suggest that duckweed plants are tolerant to environmental toxicity. Other studies, however, indicate that duckweed plants are as sensitive to toxicity as other aquatic species. Duckweed plants are especially suitable for use in complex effluent bioassays, and for testing herbicide pollution in the aquatic environment, lake and river pollution, sediment toxicity, and the like. Duckweed and algae represent different levels of complexity in the plant kingdom. They complement each other as phytotoxicity test organisms, instead of mutually excluding each other. Many duckweed species have been studied, primarily of the Lemna and Spirodela genera. Lemna minor and L. gibba have been recommended as standard test species. Differences in duckweed test methodology occur with regard to test types, test vessels, control tests, nutrient media, end points, and applications. PMID- 2190825 TI - On the domain construction of the multienzyme gramicidin S synthetase 2. Isolation of domains activating valine and leucine. AB - The multienzyme gramicidin S synthetase 2, composed of one polypeptide chain, was treated with trypsin and chymotrypsin to give fragments retaining partial enzyme activities. Previously, a tryptic fragment of this multienzyme has been identified as a structural and functional domain. In this study two more fragments, activating Leu and Val, respectively, are shown to represent domains. Careful inspection of the data on limited proteolysis, from this study as well as from previous work, suggests that domains are not simply connected like pearls on a string, and a model for the structure of gramicidin S synthetase, with implications for other peptide synthetase multienzymes, is presented. It is suggested that gramicidin S synthetase 2 is constructed from core catalytic domains and intervening framework. Such an interpretation is in accordance with all published data on limited proteolysis of peptide synthetases, but needs an interplay with gene structural studies in order to be validated and refined. PMID- 2190826 TI - Unusual proteolysis of the protoxin and toxin from Bacillus thuringiensis. Structural implications. AB - Trypsin is shown to generate an insecticidal toxin from the 130-kDa protoxin of Bacillus thuringiensis subsp. kurstaki HD-73 by an unusual proteolytic process. Seven specific cleavages are shown to occur in an ordered sequence starting at the C-terminus of the protoxin and proceeding toward the N-terminal region. At each step, C-terminal fragments of approximately 10 kDa are produced and rapidly proteolyzed to small peptides. The sequential proteolysis ends with a 67-kDa toxin which is resistant to further proteolysis. However, the toxin could be specifically split into two fragments by proteinases as it unfolded under denaturing conditions. Papain cleaved the toxin at glycine 327 to give a 34.5-kDa N-terminal fragment and a 32.3-kDa C-terminal fragment. Similar fragments could be generated by elastase and trypsin. The N-terminal fragment corresponds to the conserved N-terminal domain predicted from the gene-deduced sequence analysis of toxins from various subspecies of B. thuringiensis, and the C-terminal fragment is the predicted hypervariable sequence domain. A double-peaked transition was observed for the toxin by differential scanning calorimetry, consistent with two or more independent folding domains. It is concluded that the N- and C-terminal regions of the protoxin are two multidomain regions which give unique structural and biological properties to the molecule. PMID- 2190827 TI - Analysis of a soluble mutant des-methionine interleukin-2 receptor alpha chain (Tac protein) produced by transfected mammalian cells. AB - By using recombinant DNA technology the cytoplasmic and trans-membrane domain of the human interleukin-2 receptor alpha chain (IL-2R alpha, Tac) and of a mutant protein lacking methionine-residues 18, 25, 44, 88, 92, 126, 149, 167, 205, and 209 (des-Met IL-2R alpha) encoded by a chemically and enzymatically synthesized gene, were deleted. This leads to secretory expression of soluble wild-type and des-Met mutant Tac protein of 42-45 kDa after transfection of BHK-21 cells. Transfectants secreted up to 1.6 micrograms soluble wild-type IL-2R alpha protein/10(6) cells in 24 h into the culture medium. LTK- cell lines, expressing a large number of wild-type and des-Met mutant low-affinity IL-2R alpha of 50-55 kDa on their surface, shed a truncated form of the Tac protein of about 40 kDa into the culture medium. In contrast to wild-type IL-2R alpha, shedding of mutant Tac protein is strongly reduced. This phenomenon might be the result of higher protein stability of the mutant receptor which may also explain the about 10 times higher surface expression of des-Met IL-2R alpha in LTK- cells. There are no significant differences in the biosynthesis and post-translational modification of mutant or wild-type Tac proteins either in transfected LTK- or BHK-21 cells as analysed by pulse/chase labeling experiments. PMID- 2190828 TI - Assignment of tyrosine resonances in the 1H-NMR spectrum of tryptophan synthase alpha-subunit. Monitoring conformational changes due to substitutions at position 49. AB - In order to monitor the conformational changes of tryptophan synthase alpha subunit from Escherichia coli in solution resulting from amino acid substitutions, we have assigned the Tyr resonances in the aromatic region of the 1H-NMR spectrum to specific residues. In the spectrum of the alpha-subunit deuterated with [2,3,4,5,6-2H5]Phe and [3,5-2H2]Tyr, the C2 and C6 protons of Tyr gave completely isolated signals at acidic p2H. Some of the C3 and C5 proton resonances overlapped with each other at acidic p2H. By using a series of mutant alpha-subunits in which each Tyr was singly substituted with His or Phe, we can now assign each of seven Tyr resonances in the aromatic region to a specific residue. We have previously studied the conformational stability of a series of variant alpha-subunits at position 49 [Yutani et al. (1987) Proc. Natl Acad. Sci. USA 84, 4441-4444]. We now compare the 1H-NMR spectra in the aromatic region of the wild-type alpha-subunit and mutant alpha-subunits substituted with Phe or Gly in place of Glu-49. The results suggest that the major conformational effects of substitutions at position 49 are localized close to the position of substitution. PMID- 2190829 TI - Prospects for monoclonal antibodies in the diagnosis and treatment of bacterial infections. PMID- 2190830 TI - Incidence of early onset group B streptococcal septicemia in Sweden 1973 to 1985. AB - A retrospective investigation was made to determine the incidence of early onset group B streptococcal (GBS) septicemia in Sweden in relation to perinatal data. During the period 1973-1985 the yearly incidence of GBS septicemia increased from 0.1 to around 0.5 cases per 1,000 live births. In 416 cases verified by blood culture, the overall mortality was 15% 62/416). In babies with a birth weight of greater than 2,500 g this figure was 9.6% (29/303). In babies with a birth weight of less than 2,500 g the mortality was 29.2% (33/113). Males had a worse prognosis than females and were also more often affected. Thirty-six percent of the verified cases were premature, the gestational age being 36 weeks or less. An increased incidence among twins was also noted. PMID- 2190831 TI - Use of blocking reagent to confirm enzyme immunoassay results in chlamydial conjunctivitis. AB - A blocking reagent (Abbott) was used to test 153 conjunctival and nasopharyngeal samples from children with signs of early trachoma and from neonates and adults with conjunctivitis caused by Chlamydia trachomatis in whom positive results had been obtained on at least one occasion in an enzyme immunoassay (EIA) (Abbott). EIA and cycloheximide-treated McCoy cell cultures of the eye sample were equally often positive in the non-trachoma cases (70 versus 71), the EIA results being confirmed by the blocking reagent test in these cases. The corresponding figures for the nasopharyngeal samples were 31 versus 25. There was full agreement between the results of the EIA and blocking reagent tests, except in two eye samples and one nasopharyngeal sample where the blocking reagent test was negative. Three EIA results were within the equivocal zone around the cutoff point, two of which were positive and one negative in the blocking test. PMID- 2190832 TI - Three-dimensional electron microscopy: structure of the Golgi apparatus. PMID- 2190833 TI - Human vascular smooth muscle cells in culture: growth characteristics and protein pattern by use of serum-free media supplements. AB - This study demonstrates that cultivation of vascular smooth muscle cells from human artery wall is possible under completely serum-free conditions. The effects of attachment factors on cell spreading and cell proliferation are described in detail as well as routine cultivation methods under serum-free conditions (clone cultures, cell migration, subcultivation by use of an exogenous trypsin inhibitor, cryopreservation and readaptation of cells). After a careful adaptation period, only two (BMS and Ultroser G) of the four commercially available serum-free media supplements tested were used successfully for a routine cultivation of the smooth muscle cells over several passages. With both supplements cell proliferation rates were comparable with those obtained in medium containing 10% fetal calf serum. The addition of platelet-derived growth factor or transferrin to serum-free cultures had no growth-stimulating effect. The addition of endothelial cell growth factor isolated from bovine brain caused a significant increase in proliferative activity of cells cultivated with BMS, but not with Ultroser G. Moreover, we report that under the serum-free culture conditions described here, the gamma-actin content of the cells is largely reduced (51% +/- 13% (means +/- SD) for cells cultivated in Ultroser G, and 12% +/- 4% (means +/- SD) for cells cultivated in BMS) when compared with cells cultivated under serum-containing conditions (gamma-actin content = 100%). The alpha-actin content was observed to be unaltered. Even after a careful readaptation of serum-free cultured cells to serum conditions, the gamma-actin content remained reduced. PMID- 2190834 TI - Overexpression of tubulin in yeast: differences in subunit association. AB - Microtubules are cytoskeletal organelles composed principally of polymerized alpha beta-tubulin heterodimers. The specific roles and the detailed structures of the individual alpha- and beta-tubulin subunits have not been established, since the conditions necessary for separating the heterodimer result in loss of the subunits' ability to repolymerize. We have overcome this obstacle by constructing plasmids which allow regulated overexpression of individual tubulin subunits in the yeast Saccharomyces cerevisiae under control of the galactose promoter. Overproduction was monitored with alpha- and beta-tubulin-specific antibodies using immunoblotting of cell extracts, and the state of association of the individual subunits in vivo was determined by immunofluorescence microscopy. Cells overproducing only beta-tubulin accumulated fibrous structures associated with the cell membrane, whereas cells overproducing only alpha-tubulin displayed a diffuse signal throughout the cytoplasm. Cells simultaneously overexpressing alpha- and beta-tubulin subunits accumulated membrane-associated, filamentous arrays in which both subunits were incorporated. When cells with the fibrous tubulin-containing structures are treated with zymolyase, a yeast cell wall disrupting enzyme, the fibers appear to splay apart, suggesting that the immunofluorescent rings represent bundles of fibers. Cells overproducing beta tubulin alone or both alpha- and beta-tubulin were examined at various times after galactose induction, and significant differences were found in the tubulin association state prior to the formation of fibers. For alpha beta-tubulin, fibers form directly from a nuclear structure, whereas beta-tubulin alone first accumulates in the cytoplasm. The differences in patterns of tubulin accumulation and assembly presumably reflect a difference in the intrinsic association properties of the alpha- and beta-subunits. PMID- 2190835 TI - Secretion of a platelet-derived growth factor homologue by rat alveolar macrophages exposed to particulates in vitro. AB - Lung macrophages secrete a homologue of platelet-derived growth factor (PDGF) which induces the proliferation of fibroblasts in vitro. In previous studies, we showed that such a PDGF homologue is produced by rat alveolar macrophages and that rat lung fibroblasts have specific receptors for the macrophage-derived PDGF. In this study, we demonstrate the biological and physicochemical properties of the growth factor, as well as the time-related production of this factor following macrophage activation in vitro by organic and inorganic particles. Alveolar macrophages (AMs) collected by saline lavage from the lungs of rats were cultured in serum-free Dulbecco's modified Eagle's medium (SF-DMEM) for varying periods of time up to 72 h. The SF-DMEM "conditioned" by the AMs was used to treat early passage rat lung fibroblasts (RLFs), which were rendered quiescent by culturing in 2% platelet-poor plasma (PPP). Alveolar macrophage conditioned media (AMCM) in the presence of PPP caused increases in the number of fibroblasts, the percent of labeled fibroblast nuclei and tritiated [3H]thymidine incorporation. AMCM alone caused no detectable changes in fibroblast growth rate. These results indicate that AMs release a "competence-like" growth factor. The AMs were left untreated or were exposed to opsonized zymosan, carbonyl iron spheres or chrysotile asbestos fibers. Macrophages attached to a plastic substrate spontaneously produced the factor, and subsequent addition of the organic and inorganic particles to the macrophage cultures significantly increased the fibroblast-stimulating activity of the AMCM. The growth factor was stable after concentration (100-fold), lyophilization and reconstitution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190836 TI - Aortic regurgitation secondary to Behcet's disease. A case report and review of the literature. AB - Cardiac complications, especially aortic regurgitation, are very rare in Behcet's disease. This report describes a patient with a complicated abnormality of the aortic valve apparatus and severe aortic regurgitation secondary to Behcet's disease. In the literature, flail prolapsed valve, perforated valves and ruptured pseudoaneurysms of the sinus of Valsalva have been reported. Echocardiography may be most useful to detect these anatomically complex abnormalities and therefore to elucidate the cause of aortic regurgitation in Behcet's disease. PMID- 2190837 TI - The development of new radiopharmaceuticals. AB - The development of new radiopharmaceuticals is the basis of the continuing growth of nuclear medicine. Chemical interactions of electron clouds in their three dimensional conformations bring together, in the process of molecular recognition, the reaction of antibody and antigen, receptor and ligand, enzyme and substrate, hormone and response site. This convergence enables the computer design of molecules such as ligands to fit computer-displayed conformational models showing active centres, positive and negative charges and other interactions. Indeed, given a particular molecule, a complementary binding structure can be devised. The hybridoma approach to monoclonal antibody production is being superceded by the bacterial bioengineer. The gene for the hypervariable region from the spleen cells of immunized mouse can be coupled with the myeloma gene. The polymerase chain reaction can duplicate the DNA a million times over in 20 min and the result transfected into a bacterial plasmid to produce the antibody. These scientific problems are soluble in principle and are being solved. However, so much damage to this developing biological field is being done by regulatory authorities that one must ask who should or can regulate the regulators. These problems have to be overcome in order to provide the new radiopharmaceuticals that are the food and wine of nuclear medicine. PMID- 2190838 TI - Ultrasonically guided prostatic biopsy: technical improvements. AB - Combining the use of a longitudinal real-time transrectal ultrasound scanner (Bruel & Kjaer 8537 7 MHz Sector Scan), an attachable puncture guide (Bruel & Kjaer UA 0875) and the Biopty-Cut apparatus (Radioplast), one can now easily perform all prostatic biopsies with ultrasonic guidance. We evaluated this method in 75 patients and found it to be a most elegant and accurate method for the histological diagnosis of prostate cancer. PMID- 2190839 TI - Tamoxifen and kallikrein in therapy of oligoasthenozoospermia: results of a randomized study. AB - Because of the good results achieved with tamoxifen in the treatment of oligozoospermia and with kallikrein in the treatment of asthenozoospermia, a randomized study of the combined treatment of oligoasthenozoospermia suggested itself. 67 patients with idiopathic normogonadotropic oligoasthenozoospermia were treated with 30 mg tamoxifen/day (n = 33) or with 30 mg tamoxifen/day and additionally 600 IU kallikrein/day (n = 34). It was shown that, apart from a significant increase in sperm density in both groups, the combination therapy also resulted in an overall significant increase (p less than 0.02) in sperm motility. Sperm morphology and the swell test remained unaffected. After 3 months of therapy, 4 pregnancies occurred in each group. In ejaculates with a sperm density of less than 10 million/ml not even one sperm parameter was significantly affected in any of the groups, while with an initial value of more than 10 million/ml the increase in motility was more significant (p less than 0.008) in the group with additional kallikrein therapy (n = 18). In the monotherapy group, no significant therapeutic effect on sperm motility was seen even in patients with a sperm density of more than 10 million. The combination of tamoxifen and kallikrein therefore seems to constitute an improvement of the systemic therapy of male subfertility in patients with moderately severe oligoasthenozoospermia. PMID- 2190840 TI - Refinements in the coating of urethral catheters reduces the incidence of catheter-associated bacteriuria. An experimental and clinical study. AB - The tendency to develop bacteriuria during the use of various forms of indwelling catheters was evaluated in a randomized trial in 90 patients. A silver alloy and hydrogel-coated Foley catheter (SHC) was compared to a non-coated catheter (NC) and a catheter coated only with hydrogel (HC). Three patients (10%) with SHC catheters, 10 (33%) patients with HC catheters, and 15 (50%) patients with NC catheters developed bacteriuria (greater than 10(5) organisms/ml). The difference in the rate of bacteriuria after 5 days of catheterization was statistically significant between the SHC catheter and the NC catheter (p less than 0.002). There was no significant difference between the SHC catheter and the HC catheter, nor was there a significant difference between the HC catheter and the NC catheter. The toxic effects, as estimated by the IC50 value, of the urinary catheter material used was elucidated in an experimental fibroblast model. The IC50 value for the NC catheter was 33.9%, HC catheter 72.2% and for the SHC catheter 98.1%. PMID- 2190841 TI - Comparison of microsurgical vasovasostomy techniques in the rat. AB - We compared three different microsurgical vasovasostomy techniques on the rat vas deferens using absorbable and non-absorbable sutures and a fibrin adhesive technique. The best method was an extramucosal technique over a splint using vicryl. The worst results were seen using adhesive. PMID- 2190842 TI - Alkali citrate for preventing recurrence of calcium oxalate stones. AB - The use of alkali citrates for preventing the recurrence of calcium oxalate stones was investigated in two trials. In trial I, alkali citrates were given continuously for 18 months to 8 patients who had shown a tendency to recurrent stone formation. In trial II, 12 similar patients were given intermittent therapy for 12 months. The expected changes in urine chemistry were checked at intervals of 3 months. Recurrent stone formation (2 episodes) was observed in only 1 patient (in trial II) during alkali citrate administration; before therapy this patient had suffered an average of 10 attacks of stone formation annually. In the light of the experience gained in these trials, continuous administration of alkali citrates is recommended; the duration of treatment should be tailored to individual needs, but it should not be prolonged indefinitely. Besides having well-attested effectivity of stone prevention, this mode of therapy carries a relatively low incidence of side effects. PMID- 2190843 TI - Effects of attritive diet on craniofacial morphology: a cephalometric analysis of a Finnish skull sample. AB - The purpose of the present study was to analyse cephalometrically the effects of a high-attrition environment on craniofacial morphology. The material consisted of lateral cephalograms of 32 Finnish crania and of a control sample of 50 present-day Finns. The skull sample represented Finns who had lived in the city of Turku during the 15th and 16th centuries. Marked dental attrition was seen in the skulls; the dentition of the control individuals was virtually unworn. The gonial angle, and the angle between the mandibular base and nasal floor were significantly smaller in the skull sample than in the present-day sample. In addition, the upper incisors were more palatally inclined, and the angle between the axes of the upper and lower incisors was significantly larger in the skull sample. The configuration of the cranial base, and the relationship of the clivus to the nasal floor and ramus were similar in both samples. The results indicate that intensive mastication affects mandibular growth by advancing its anterior rotation. The large interincisal angle was caused, almost equally, by the lingual tipping of the upper incisors and the anterior rotation of the mandible. It is suggested that anterior rotation is the natural growth direction of the mandible. However, several functional disturbances, including reduced masticatory stimulation due to modern diet, may promote more posteriorly directed growth. PMID- 2190844 TI - Creutzfeldt-Jakob disease and kuru patients lack a mutation consistently found in the Gerstmann-Straussler-Scheinker syndrome. AB - We and others have recently reported that patients with the Gerstmann-Straussler Scheinker syndrome have a mutation at codon 102 of the gene coding for amyloid protein that accumulates in this disease. We report here that this mutation was not found in 5 familial and 27 sporadic cases of Creutzfeldt-Jakob disease or in 3 patients with kuru, so that although this mutation may be responsible for amyloidogenesis and transmissibility in Gerstmann-Straussler-Scheinker syndrome, it cannot be the only cause of human spongiform encephalopathy. PMID- 2190845 TI - Epidemiological aspects of abdominal aortic aneurysm. PMID- 2190846 TI - Immediate detection of postreconstructive ischaemia by intra-operative Doppler ankle pressure index monitoring during aortic reconstructions. AB - From March 1980 to February 1988, 368 aorto-iliac or aorto-femoral bilateral reconstructions were performed for aneurysmal or occlusive disease. In order to demonstrate early postreconstructive ischaemic complications, the intra-operative Doppler Ankle Pressure Index (API) was measured immediately before reconstruction (PRE), just after declamping (DEC) and 5, 15, 30 and 45 min thereafter. Each limb of the reconstruction (736) was considered individually and subdivided as follows: Group (A) 705 immediately successful (96% of limbs and 92% of patients); Group (B) 22 (3% of limbs and 5% of patients) in which, on the grounds of API data, an ischaemic complication was regarded as imminent and treated by graft revision or a peripheral thromboembolectomy (intra-operative corrections); Group (C) 9 (1% of limbs and 2% of patients) in which the diagnosis of ischaemic complications was made postoperatively when the patients underwent successful reoperation. All 736 reconstructions were patent and functional at discharge of the patient. By a retrospective analysis the intra-operative APIs were studied and the features (single or associated) suggesting an ischaemic complication examined. These were: (1) no flow at the time of declamping or its disappearance during the operation (10 cases, 1.25% of limbs) all detected and successfully corrected intra-operatively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190847 TI - A haemodynamic evaluation of the femoro-femoral cross-over bypass. AB - The femoro-femoral cross-over bypass has become a popular choice for the management of unilateral iliac artery disease, being used in preference to aorto femoral or extraperitoneal ilio-femoral bypasses. It is a relatively minor procedure and associated with a small incidence of side effects, the main one being the risk of development of a steal of blood from the donor limb by the bypass. Although this problem has been widely discussed, haemodynamic studies have been limited by the use of indirect measurements of blood flow, such as ankle systolic pressures or by the use of electromagnetic flowmetry at the time of surgery. No study employing volumetric blood flow measurements to identify and quantify blood steal in the postoperative patient has been reported to date. With aims of studying the haemodynamic effects of a femoro-femoral cross-over bypass on the circulation in both the recipient and donor limbs, and of identifying preoperatively, problems likely to lead to haemodynamic problems or to graft failure, the present study of 31 patients undergoing femoro-femoral bypass was undertaken. The patients, 18 of whom had rest pain and 13 intermittent claudication, were studied preoperatively using arteriography and a non-invasive assessment. At 3 months from the operation, all received a clinical assessment and a further non-invasive assessment, including a measurement of blood volume flow. Flow measurements were made in the bypass at rest and during a reactive hyperaemia test. In addition, flow measurements were made in the donor limb below the bypass origin at rest and during hyperaemic testing of the recipient limb in order to assess any steal effect the bypass might cause to the donor limb circulation. All 31 patients were improved by surgery, but five developed donor limb claudication which was attributed to steal in three cases. Resting blood flow in the bypasses, 161 (65-282)ml/min [median (range)], rose by 116% (5-428%) to 300 (82-1114)ml/min after hyperaemic testing. Simultaneously, bypass hyperaemia caused a fall in donor limb blood flow of 32% (0-74%). Of the preoperative non-invasive tests, only donor femoral artery pulse rise time was related to the later development of objective evidence of steal. Successful Gruntzig dilatation of four major stenoses resulted in a satisfactory outcome. PMID- 2190848 TI - The correlation between clinical and duplex ultrasound parameters and the development of complications in arterio-venous fistulae for haemodialysis. AB - In a 2 year prospective study of the fate of arterio-venous haemodialysis fistulae, the influence of several clinical and non-invasive measured variables in 90 patients on maintenance haemodialysis was evaluated. A total of 58 Brescia/Cimino fistulae, 30 graft fistulae and two elbow fistulae were investigated by means of Duplex ultrasound scanning. Sixty-two out of these 90 patients had no problems with their AV fistulae, 28 developed 29 complications, including poor flow (six), thrombosis (seven), venous hypertension (eight), false aneurysm formation (four), distal ischaemia (two) and puncture problems (two). Univariate statistical analysis was performed on a number of clinical variables including diabetes, previous access surgery, type of fistula, duration of functioning fistula, congestive heart failure, peripheral arterial disease, age and sex. Results indicated that the type of fistula, previous access surgery, congestive heart failure and sex were significantly correlated to the development of poor flow and thrombosis (flow-related complications). Measurement of the maximal systolic frequency, end-diastolic frequency and the frequency ratio in the brachial artery Doppler spectrum, was of prognostic value in discriminating between non-complicated fistulae and those which developed flow-related complications. The total number of fistula stenoses (greater than 50% diameter reduction), detected by the Duplex scan, also correlated with the rate of thrombosis and poor flow. The presence of peripheral arterial disease and the number of stenoses in the efferent veins were of predictive value for the development of venous hypertension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190849 TI - Current status and future prospects of transdermal estrogen replacement therapy. PMID- 2190850 TI - Healing of grade-II and III oesophagitis through motility stimulation with cisapride. AB - The clinical relevance of cispride's stimulating effects on lower oesophageal motility was studied in 19 patients with documented (endoscopy, biopsy) grade II or III oesophagitis. Patients were treated for 8 or 16 weeks (depending essentially on whether the result was cure or failure) with 10 mg of cisapride four times a day (n = 11) or placebo (n = 8). Cisapride was superior to placebo with regard to mucosal healing (p less than 0.001) and symptomatic improvement (p less than 0.05): at the end of treatment, healing (grade 0) was observed in 8 cisapride patients, against 1 placebo patient, and reflux symptoms had disappeared in 7 and 1 patients, respectively. In conclusion, cisapride was of significant benefit to oesophagitis patients and was well tolerated. PMID- 2190851 TI - Slow-release 5-amino-salicylic acid (Pentasa) for the treatment of active Crohn's disease. AB - A double-blind, placebo-controlled trial of a slow-release preparation of 5-amino salicylic acid (Pentasa) has been performed in 40 patients with active Crohn's disease. Over a 6-week period, Pentasa (1.5 g daily) was no different to the dummy tablet in terms of clinical activity (Harvey-Bradshaw Index) or laboratory indicators of inflammation. No serious adverse reactions occurred. PMID- 2190852 TI - The effects of enterotoxins and short-chain fatty acids on water and electrolyte fluxes in ileal and colonic loops in vivo in the rat. AB - The effect of cholera toxin (CT) and Escherichia coli heat-stable enterotoxin (ST) on the ileum and colon was examined in vivo in the rat in an attempt to clarify the effects of enterotoxins on colonic mucosa and to determine if these effects were influenced by short-chain fatty acids (SCFA). Both CT and ST induced similar changes in water and electrolyte fluxes, and the magnitude of these changes in loops of colon was similar to that observed in loops of ileum. The addition of luminal SCFA, acetate, propionate and butyrate did not influence the effect of either toxin in loops of ileum. However, in loops of colon exposed to CT, luminal butyrate (40 mM) largely reversed the effect of CT by converting net water secretion (mean +/- SE, -363 +/- 154 nl.cm-2.min-1) to net water absorption (470 +/- 194 nl.cm-2.min-1) and by significantly reducing the net secretion of sodium ions. In loops of colon exposed to ST, similar effects were observed although net water secretion (-784 +/- 114 nl.cm-2.min-1) was only partially reversed by butyrate (-318 +/- 102 nl.cm-2.min-1). In contrast to butyrate, acetate and propionate did not influence changes in colonic fluxes of water and sodium induced by enterotoxins. Oxidation of butyrate and glucose was observed to be depressed in colonocytes pre-exposed to CT but not to ST. In this model, colonic secretion induced by enterotoxins is similar to that observed in the ileum but differs from ileal secretion in its modulation by luminal butyrate. PMID- 2190853 TI - [Primary biliary cirrhosis: current modes of presentation. Clinical, biochemical, immunologic and histologic study of 206 patients seen from 1978 to 1988]. AB - The aim of this study, based on a series of 206 patients (186 women and 20 men) with primary biliary cirrhosis seen from 1978 to 1988, was to assess the current modes of presentation of the disease. In approximately 30 percent of patients, primary biliary cirrhosis was recognized at an asymptomatic stage. Two thirds of these patients remained asymptomatic: they were older (mean age 57 years) and had less severe histological lesions than the patients who became symptomatic (mean age 45 years). The modes of presentation were not markedly different in the male and female patients of our series. The prevalence of cholelithiasis seemed to be particularly high (more than 20 percent in our patients). Complications of portal hypertension (bleeding esophageal varices or ascites) were the initial manifestations of primary biliary cirrhosis in 8 percent of our symptomatic patients. Alkaline phosphatase level was normal or only slightly increased in 15 percent of our patients: a normal level or a slight increase in alkaline phosphatases is not an argument against the diagnosis of primary biliary cirrhosis. Antinuclear antibodies with perinuclear fluorescence were demonstrated in 26 percent of our patients; in most of these patients, an antibody to a 200 kD protein of the nuclear envelope was present; in patients with this antibody, asthenia, arthralgias and associated extrahepatic diseases were less common and the titers of antibodies to mitochondria were lower than in the patients without this antibody. PMID- 2190854 TI - [Nuclear envelope autoantibodies and liver diseases]. PMID- 2190855 TI - [A joint study of mutation of the Ki-ras oncogene and overexpression of the Tp53 oncogene in colorectal cancer]. AB - Twenty-five colorectal tumors (rectum 6, left colon 13, right colon 6) were studied with respect to the overexpression of p53 and the activation by point mutation of the Ki-ras oncogene. Single point mutations on codon 12 and codon 13 were analyzed after PCR amplivication, dotblotting and sequential hybridization with 12 different oligonucleotides. The intranuclear concentration of p53 protein was measured by flow cytometry after immunofluorescence staining with monoclonal antibody Pab 421. Twelve tumors were found to significantly overexpress p53 and 6 of them had an activated Ki-ras (5 on codon 12, 1 on codon 13). Of 13 tumors which failed to demonstrate over expression of p53, 8 had an activated Ki-ras (5 on codon 12, 3 on codon 13). In our series, p53 overexpression and ki-ras activation appeared to be independent. PMID- 2190856 TI - [The gastrointestinal mucus: a complex protective barrier. 1: Structure and physico-chemical properties]. PMID- 2190857 TI - [Carney's triad: a new case associated with adrenal cortex adenoma]. AB - Carney's triad is a combination of at least 2 of 3 tumor sites: multiple gastric leiomyoblastoma, pulmonary chondroma and paraganglioma, most often extra-adrenal and secreting. Thirty-three cases have been published; we report a new case in a 20 year-old woman, with multiple gastric leiomyoblastomas, liver metastasis, and bilateral pulmonary chondroma. The research of paraganglioma, in regard to Carney's disease, led to the discovery of corticoadrenal adenoma. PMID- 2190858 TI - [Comparative measurement of the pedicle common bile duct by echography and endoscopic retrograde cholangiography in chronic calcifying pancreatitis]. PMID- 2190859 TI - [Basal blood gastrin is normal during the long-term preventive treatment of recurrence of duodenal ulcer with ranitidine 150 mg daily]. PMID- 2190860 TI - [Comparative hygienic characteristics of surface-active agents as a factor of environmental pollution (review)]. PMID- 2190861 TI - [Accelerated methods for studying gonadotoxic effects of substances]. PMID- 2190862 TI - Sir Francis Avery Jones at 80. PMID- 2190863 TI - Cancer of the pancreas. PMID- 2190864 TI - Double blind comparison of omeprazole (40 mg od) versus cimetidine (400 mg qd) in the treatment of symptomatic erosive reflux oesophagitis, assessed endoscopically, histologically and by 24 h pH monitoring. AB - This double blind, double dummy study compares the rate of healing of erosive reflux oesophagitis, assessed endoscopically, with four and eight weeks treatment using omeprazole or cimetidine, and the effect of four and eight weeks treatment of reflux oesophagitis with omeprazole or cimetidine on reflux symptoms, microscopic healing, and in a subgroup of patients, oesophageal pH measurements. Omeprazole 40 mg once daily achieves (i) greater and more rapid symptom relief, (ii) more rapid and sustained endoscopic and histological healing, and (iii) greater reduction of oesophageal acid exposure than cimetidine 400 mg four times daily. PMID- 2190865 TI - Abolition by omeprazole of aspirin induced gastric mucosal injury in man. AB - This study investigates whether aspirin injury to the human gastric mucosa can be prevented by profound acid suppression with omeprazole, in a randomised, double blind, crossover design according to latin square. It was concluded that profound acid suppression can prevent aspirin induced gastric mucosal injury in normal subjects. This approach may prevent the development of peptic ulcers and their complications in patients taking aspirin and other non-steroidal anti inflammatory drugs. PMID- 2190866 TI - Antibody to selected strains of Saccharomyces cerevisiae (baker's and brewer's yeast) and Candida albicans in Crohn's disease. AB - IgG serum antibody was measured by ELISA in patients with Crohn's disease (15), ulcerative colitis (15), and in normal controls (15) to 12 strains of Saccharomyces cerevisiae (baker's and brewer's yeast) and to the two major serotypes of the commensal yeast Candida albicans. Antibody to 11 of the 12 strains of S cerevisiae was raised in patients with Crohn's disease but not in patients with ulcerative colitis when compared with controls (p less than 0.001). The pattern of antibody response to these 11 strains was variable, however, suggesting the likelihood of antigenic heterogeneity within the species. Antibody to C albicans was not significantly different in patient and control groups. The specificity of this unusual antibody response in Crohn's disease for S cerevisiae suggests that it is not simply the result of a generalised increase in intestinal permeability. Furthermore, because brewing and baking strains detected the response, the relevant antigen(s) are presumably common in the diet. Hypersensitivity to dietary antigens may be involved in the pathogenesis of Crohn's disease, and the role of S cerevisiae requires further investigation. PMID- 2190867 TI - Villous adenoma of the common hepatic duct: the role of ultrasound in management. AB - A case of villous adenoma of the common hepatic duct causing obstructive jaundice, where the diagnosis was made by ultrasound guided percutaneous biopsy is reported. At surgery ultrasonography was used to define the extent and operability of the tumour. PMID- 2190868 TI - Interactions between gall bladder bile and mucosa; relevance to gall stone formation. PMID- 2190870 TI - Does serum CA-125 level prior to second-look laparotomy for invasive ovarian adenocarcinoma predict size of residual disease? AB - The records of 125 patients with nonmucinous invasive ovarian adenocarcinoma who underwent cytoreductive surgery, cisplatin-based combination chemotherapy, and second-look laparotomy were analyzed to correlate pre-second-look serum CA-125 levels with the size of residual ovarian cancer. The majority of patients with negative second-look laparotomy had normal serum CA-125 levels (46/50 or 92%). Of the 75 patients with positive second-look, 56 (75%) had normal CA-125 levels preoperatively. Twenty-three of twenty-four (96%) patients with residual disease less than or equal to 1 cm had normal CA-125 levels as did 20 of 28 (71%) patients with disease 1.1-2.0 cm. Although elevated serum CA-125 levels were invariably associated with visible/gross disease and increasing size of residual disease tended to be associated with increasing elevations of CA-125, normal CA 125 levels often occurred in the presence of large-volume (greater than 2 cm) disease (13/23, 57%). The considerable overlap of serum CA-125 levels for all sizes of residual disease precluded precise prediction of residual disease size based on serum CA-125 level alone. PMID- 2190869 TI - Biliary motility. PMID- 2190871 TI - Localization of leukocytes and cytokines in chorionic villi of normal placentas and complete hydatidiform moles. AB - Monoclonal antibodies were used to localize and characterize leukocytes and cytokines in chorionic villi of normal placenta and complete mole. OKT4a reacted with Hofbauer cells in first-, second-, and third-trimester placentas. HLA-DR was expressed on second- and third-trimester placental Hofbauer cells but was not detected in the first trimester. The cytokines, gamma-interferon, granulocyte macrophage colony-stimulating factor, interleukin-1 alpha, and tumor necrosis factor alpha, were all detectable on Hofbauer cells in first-, second-, and third trimester placentas. None of the tested cytokine antibodies reacted with cellular constituents in complete molar chorionic villi. The absence of cytokine-positive cells in molar chorionic villi may be related to the hyperplastic and unregulated growth of molar villous trophoblast. PMID- 2190872 TI - Successful therapy of metastatic embryonal carcinoma coexisting with gonadoblastoma in a patient with 46,XY pure gonadal dysgenesis (Swyer's syndrome). AB - A case of gonadoblastoma associated with metastatic embryonal carcinoma occurring in a phenotypic female with 46,XY pure gonadal dysgenesis is presented. Two years after treatment with surgery and combination chemotherapy the patient is disease free. This is the third reported case and first reported cure in the English language literature over the past 25 years. Current management is reviewed. PMID- 2190873 TI - A patient with multiple, malignant melanomas of the lower genital tract. AB - Malignant melanomas of the female genital tract are uncommon lesions. A patient with multiple cutaneous, vulvar melanomas and a subsequent malignant melanoma of the cervix is described. PMID- 2190874 TI - Ovarian carcinoma metastatic to breast: a case report and review of the literature. AB - Breast metastasis from ovarian carcinoma is a rare event, with only 26 cases being previously reported in the English literature. The twenty-seventh such case is presented herein, and the literature on this topic is reviewed. Metastases to the breast from the ovary signal widespread metastases and generally herald a rapid deterioration and death. Although rare, it is important that metastatic cancer to the breast be differentiated from primary breast carcinoma as both the treatment and prognosis differ significantly. PMID- 2190875 TI - Rhabdomyosarcoma of the uterus in a postmenopausal patient. AB - Pure rhabdomyosarcomas of the female genital tract most commonly occur in infancy or childhood as sarcoma botryoides (embryonal rhabdomyosarcoma) and involve the vagina and cervix. Such tumors rarely occur in adults. A pure rhabdomyosarcoma of the uterus that arose in a postmenopausal patient is described. The pertinent literature is discussed. PMID- 2190876 TI - Human placental insulin binding in normal and well-controlled diabetic patients. AB - Previous studies of insulin binding to placentas of both insulin-dependent and untreated gestational diabetic patients have described placentas from diabetics to contain fewer insulin receptors than placentas from nondiabetic gravidas. However, these studies were done using membrane fractions prepared from the placentas and at a time when adequacy of antepartum glycemic control in the diabetic patients was not routinely evaluated by self blood sugar measurement or hemoglobin A1 assay. The current study compares specific 125I-insulin binding in vitro to intact placental villi from 15 normal patients with insulin binding to intact villi obtained from 15 insulin-dependent diabetic mothers whose fasting and postprandial blood sugars and hemoglobin A1 levels were maintained in a range normal for term pregnancy. We demonstrate that insulin binding to intact placental villi is the same in this group of diabetic patients as in the nondiabetic patients. PMID- 2190877 TI - Detection of intrauterine growth retardation based on measurements of size of the liver. AB - A total of 646 ultrasonic measurements of fetal liver size were made from 18 weeks of gestation through to term. After 29 weeks, size of the liver in the growth-retarded fetuses was significantly small as compared to findings in the control fetuses. The sensitivity and specificity for the detection of growth retardation were 0.86 and 0.89 at 33 weeks, 0.89 and 0.94 at 38 weeks and 0.89 at 40 weeks of gestation. Growth rate of the liver in the growth-retarded fetus was diminished as compared with findings in the control fetus. Also, a method of estimating fetal weight by ultrasonic measurement of the fetal liver size is described. PMID- 2190878 TI - Efficiency of transvaginal scanning in obstetric and gynecologic fields. AB - Transvaginal ultrasonography was done on 26 pregnant women ranging from 5 to 27 weeks of gestation and 12 patients with gynecologic diseases. In early gestation, significant correlations were found among gestational age, crown-rump length, diameter of yolk sac and fetal heart rate. The maximal length of the gestational sac did not correlate with any other parameter. Transvaginal image quality was better in 76.2% in obstetric field and in 66.7% in gynecologic field, as compared to findings with conventional abdominal ultrasonography, respectively. Fine structures and individual organs were better evidenced transvaginally. Therefore, transvaginal ultrasound affords pertinent information complementary to that obtained with the transabdominal technique. PMID- 2190879 TI - The validity of gynecological ultrasonography. AB - The present study was undertaken to examine the reliability of the sonographic diagnosis in 705 gynecological patients. The determination of the lesions was defined according to the operative diagnosis. The sensitivity, specificity and positive predictive value of the ultrasound technique were evaluated using the surgical findings as 'gold standard'. In 631 patients (89.5%) the ultrasound examination established a correct diagnosis. The sensitivity and specificity of the ultrasound examination varied between 75-95.3% and 93.3-100%, respectively. The positive predictive value was found between 89.7 and 100%, while the false sonographic results were 10.4%, which included those of ectopic pregnancies. It is thus concluded that ultrasonography as compared to the surgical findings has proved to be of great value in establishing a gynecological diagnosis. PMID- 2190880 TI - Antenatal sonographic diagnosis of exencephaly. AB - We herein present a case of exencephaly with rachischisis, situs ambiguous and club feet, diagnosed antenatally by ultrasound. This combination of anomalies is very rare. PMID- 2190881 TI - Processing and manipulation of human hemopoietic stem cells. The Italian Cooperative Study Group on Cell Manipulation in Hematology. AB - In this paper, we reviewed the basic principles and methods of collection, processing and manipulation of marrow and peripheral haemopoietic progenitor cells. The advances in cell separation are due to the progress in blood bank technology and to the introduction of more sophisticated devices. This allows to process larger amounts of blood or marrow and to obtain a final single cell suspension. For this purpose, several procedures have been employed, including the unit gravity sedimentation, the centrifugal elutriation, the isopyknic sedimentation and the positive selection on columns of CD34+ cells. As expected, the emerging problems are the extreme heterogeneity of the methods employed and the unreliability of the quality control. The proposal for standardized protocols for each step of the various procedures is urgent, and the institution of multicenter studies is recommended. PMID- 2190882 TI - Role of recombinant human granulocyte-macrophage colony stimulating factor for large scale collection of peripheral blood stem cells for autologous transplantation. AB - Twenty-seven cancer patients underwent peripheral blood stem cell apheresis during hematopoietic regeneration following induction high-dose cyclophosphamide (7 g/sqm; HD-CTX). Among these patients, eleven were also treated with granulocyte-macrophage colony stimulating factor (rhGM-CSF) for 14 days after HD CTX. We describe technique, peripheral blood cell yields and side effects of 76 leukaphereses performed using a continuous-flow blood cell separator COBE 2997. Leukaphereses, carried out through 2-5 consecutive days per patient, were started significantly earlier in rhGM-CSF treated patients. In comparison to patients receiving HD-CTX only, administration of rhGM-CSF resulted in a significantly higher yield per leukapheresis of mononuclear cells and granulocyte-macrophage colony forming units (CFU-GM) (two-fold and eight-fold, respectively). Procedures were completed and well tolerated in all cases. Minor side effects were unfrequent. Our results suggest that rhGM-CSF accelerates hematopoietic recovery after HD-CTX and facilitates large-scale collection of peripheral blood stem cells utilizable for autologous transplantation. PMID- 2190883 TI - A preliminary survey of Italian experience on bone marrow harvesting, processing and manipulation. The Italian Cooperative Study Group on Cell Manipulation in Hematology. AB - The following report describes the initial stage of the activity of the Italian Cooperative Study group on cellular manipulation in hematology consisting of a retrospective evaluation of data regarding bone marrow (BM) harvesting processing, and proceedings from 20 Italian Centers. Two thousand, three hundred and eighty-four BM have considered: 1073 were performed for autografts and 1311 for allografts. A cohort of adverse effects in marrow harvesting were reported by 7 Centers out of 20, including one death caused by tracheomalacia during the anesthesia. Twelve Centers used blood separators as a mean for marrow processing. Eight Centers used the RBC removal technique in major donor/recipient AB0 incompatibility. Ficol-Hipaque gradient was employed in 7 Centers. T-depletion were accomplished with monoclonal antibodies in 7 Centers and elutriation in two Centers. Fifteen Centers provided to purge the residual tumour cells with chemicals (11), immunological (4) and chemo-physical means (1). PMID- 2190884 TI - Heterogeneity of circulating hematopoietic progenitors in cancer patients treated with high-dose cyclophosphamide and recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF). AB - Antigen CD34+ cells represent 1-4% of adult bone marrow cells comprising virtually all hematopoietic colony-forming progenitors in-vitro and probably also stem cells capable of restoring hematopoiesis of lethally irradiated hosts. We report that sizable numbers of CD34+ cells transiently circulate in the peripheral blood (PB) of patients treated with high-dose (7 g/sqm) cyclophosphamide (HD-CTX) with or without recombinant human glycosylated granulocyte macrophage colony stimulating factor (rhGM-CSF). Evidence is presented demonstrating that CD34+ cells from PB possess qualitatively normal hematopoietic colony growth and high cloning efficiency similarly to marrow CD34+ cells. In addition, CD34+ cells from PB are shown to display heterogeneous flow cytometry characteristics and differentiation antigens analogous to those from bone marrow, i.e., CD34+/CD33-, CD34+/CD13-, CD34+/CD38-, CD34+/CD11b, CD34+/DRlow+ cells have light scatter properties of small lymphocytes while CD34+/CD33+, CD34+/CD13+, CD34+/CD38+, CD34+/CD11b+, CD34+/DRhigh+ cells have light scatter properties of blast-like cells. In HD-CTX treated patients, CD34+ cell circulation is 5-fold enhanced by rhGM-CSF 5.5 micrograms/kg/day by continuous iv infusion for 14 days. During the second-third week after HD-CTX, large-scale collection of PB leukocytes by 3-4 continuous-flow leukaphereses allows the yield of 2.19-2.73 x 10(9) or 0.45-0.56 x 10(9) CD34+ cells, depending on whether or not patients receive rhGM-CSF. The number of CD34+ cells retrieved from PB by leukaphereses exceeds the number that can be harvested by multiple bone marrow aspirations under general anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190886 TI - [Duodenal duplication cyst]. AB - Duodenal duplication cysts are rare and are usually found in neonates or young children who present with obstructive symptoms. It accounts for 4-12% of all duplications in the gastrointestinal tract. The rate of other developmental abnormalities has been reported as high as 38%. In few instances have duodenal duplication cysts been described in adults. A case of duodenal duplication cyst in a 46-year-old woman is presented. The diagnosis was established preoperatively by computerized tomography and ultrasound examination. PMID- 2190885 TI - High-dose cyclophosphamide in patients with operable breast cancer: recombinant human GM-CSF ameliorates drug-induced leukopenia and thrombocytopenia. AB - Seventeen patients with breast cancer (nine patients with 10 ipsilateral metastatic axillary nodes, eight patients with inflammatory breast carcinoma) previously untreated with cytotoxic chemotherapy received high-dose cyclophosphamide, 7 g/sqm (HD-CTX) as initial step of a high-dose sequential chemotherapy program. Eleven patients received also intravenous recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF), 5.5 micrograms/kg per day for 7-14 days after HD-CTX. This growth factor significantly ameliorated leukopenia and thrombocytopenia induced by HD-CTX therapy thus allowing earlier delivery of subsequent courses of chemotherapy. PMID- 2190887 TI - [Crush syndrome]. PMID- 2190888 TI - [Crush injuries]. PMID- 2190889 TI - [Synoviorthesis, chemical and radiation synovectomy in rheumatic disease]. PMID- 2190890 TI - [Interleukin-6: biological characteristics and clinical importance]. PMID- 2190892 TI - [Bronchopulmonary dysplasia: prevention]. PMID- 2190891 TI - [Peripheral artery catheterization--methods, indications, complications]. PMID- 2190893 TI - [Multiple primary malignant tumors occurring in the same patient]. PMID- 2190894 TI - [Cough and angiotensin converting enzyme inhibition]. PMID- 2190895 TI - [Serum amyloid A (SAA) in rheumatic diseases and in systemic amyloidosis]. PMID- 2190896 TI - [Obstructive airway diseases--emphysema. Diagnosis and therapy]. AB - Spirometric examinations are suitable for the diagnosis of airway obstruction, but not of pulmonary emphysema. Whole body plethysmography, in contrast, is the most reliable diagnostic procedure for both conditions, both qualitatively and quantitatively. The basic treatment of any form of airway obstruction consists in the inhalation of beta-2-sympathomimetic drugs; theophyllines are also good bronchodilators, but are less powerful than beta-2-sympathomimetics. Glucocorticoids must always be given when bronchitis also presents, which is only rarely treatable with antibiotics alone. Although regression of pulmonary emphysema is not possible, progression of the destructive process would appear to be inhibited by intensive treatment of the inflammatory bronchitis. Only in the case of patients with congenital alpha-1-antitrypsin deficiency is it possible to administer such causal treatment in the form of substitution therapy. Surgical treatment can be considered only in the case of bullous pulmonary emphysema. PMID- 2190897 TI - [Roxithromycin versus doxycycline in the treatment of cervicitis. Prospective randomized multicenter study under practice-related conditions]. AB - In a prospective randomized multicenter study Roxithromycin 150 mg or Doxycycline 100 mg was given b.i.d. p.o. for ten days to women with clinically diagnosed cervicitis. All women were seen as outpatients by one of eight licensed gynecologists in their private office in the Essen city area. With a cure and improvement rate of 100% in those women who completed therapy, Roxithromycin (n = 106) was as effective as Doxycycline (n = 104; 98%). At 90% Roxithromycin was as well tolerated as Doxycycline at 93%. Both drugs were clinically and microbiologically effective in eradicating Chlamydia trachomatis. PMID- 2190898 TI - [A chance for conservative treatment of reflux disease. Can it be used preventively in malignant changes?]. PMID- 2190899 TI - [Treatment of chronic-obstructive upper abdominal complaints. Outlook. Further hypothetical indications]. PMID- 2190900 TI - Pyroglutamic acid improves the age associated memory impairment. AB - Pyroglutamic acid (PCA) was compared with placebo in a randomized, double blind trial for assessing its efficacy in treating memory deficits in 40 aged subjects. Twenty subjects were treated with PCA and 20 with placebo over a period of 60 d. Memory functions were evaluated at baseline and after 60 d of treatment by means of a battery made up of 6 memory tasks. The results suggest that PCA is effective in improving some verbal memory functions in subjects affected by age-related memory decline. PMID- 2190901 TI - The programmable implantable medication system (PIMS): design features and pre clinical trials. AB - This report describes the clinically significant design features of a variable rate implantable insulin infusion pump, the Programmable Implantable Medication System (PIMS), and its function in pre-clinical trials. PIMS has a number of unique features, including a solenoid, pulsatile pump design requiring minimal power (less than 15 microwatts) and a less-than-atmospheric pressure reservoir. Two-way communication is accomplished by radiotelemetry. The implanted device stores programs, and records its own hourly history of insulin delivery. Limits are set on total insulin delivery over time. Basal rates are adjustable, and patterned prandial insulin delivery curves can be programmed. Initial trials (3.1 dog-years) identified four problems which were corrected prior to final pre clinical trials: microcracks in the diaphragm, a valve-seating leak, electronic failure of prototype microchips, and insulin aggregation. Sixteen dog-years of final pre-clinical trials with a single system design demonstrated that 5 pumps were still working continuously after up to 3.75 years (mean 3.3 years) without mechanical or electronic pump failure. The longest interval between reservoir refills was 5 months. Remaining potential causes of flow stoppage, however, include blockage of the peritoneal catheter by omentum (which occurred once), and air lock (which occurred two times). PMID- 2190902 TI - Disappearance of opioidergic tone on LH secretion in underfed prepubertal sheep. AB - A study was conducted to determine whether an opioid tonus inhibitory of LH secretion is present in underfed prepubertal sheep. Ten Suffolk ewe lambs were subjected to food restriction during 60 days. During this period they were allowed to pasture only 2 hours per day while control ewe lambs were allowed for 10 hours. Body weight and plasma blood levels of glucose, urea and total proteins were measured weekly. At the end of this period, an intravenous injection of Naloxone (NAL, 1.5 mg/kg BW) was given to control and underfed animals followed 60 min later by an intravenous injection of LHRH to test the pituitary responsiveness. Underfed animals did not show an increase in plasma LH while control animals presented a rise from 0.28 +/- 0.08 to 2.02 +/- 0.6 ng/ml after the NAL stimulus (P less than 0.05). The response to LHRH was similar in both group of animals. Basal plasma levels of insulin were lower in underfed ewe lambs than in control animals (P less than 0.05). Underfed animals were placed on plain feeding with a schedule similar to control lambs for 30 days and the same experiment was repeated. During this occasion, NAL increased plasma LH concentration in both group of lambs. Levels of plasma insulin were not different in both groups. The lack of effect of NAL on LH secretion in food restricted ewe lambs suggests that the opioid modulation of LH secretion is absent by underfeeding in female prepubertal sheep.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190903 TI - Arginine vasopressin response to insulin-induced hypoglycemia in insulin dependent diabetics with asymptomatic hypoglycemia. AB - Insulin-induced hypoglycemia causes an increase in plasma vasopressin (AVP) in healthy subjects but the response in diabetics is not established. We investigated the effect of insulin-induced hypoglycemia on ten insulin-dependent diabetics with asymptomatic hypoglycemia, and compared the results with those for seven healthy subjects. The lack of adrenergic symptoms of hypoglycemia in insulin dependent diabetics being attributed to a diminished beta-adrenergic sensitivity, the effect of isoprenaline infusion was investigated as control. Insulin-induced hypoglycemia resulted in both populations in significant increase (P less than 0.01) in AVP in addition to significant increases in heart rate, plasma epinephrine (E), norepenephrine (NE) and cortisol (COR). Effective osmolality and mean arterial blood pressure did not vary. Diabetics showed smaller increase in AVP (P less than 0.01) and heart rate (P less than 0.05) than controls. Maximal E, NE and COR values did not differ between the two populations. Isoprenaline infusion resulted in increase in heart rate and plasma renin activity, but AVP and COR did not vary in the two populations. In conclusion, insulin-induced hypoglycemia released AVP in diabetics with asymptomatic hypoglycemia, but the response was weaker than in healthy subjects. A causal hypothalamic alteration of beta-adrenergic or glycopenia sensitivity is discussed. PMID- 2190904 TI - High Medicare hospitals seek fair share from Congress. AB - Hospitals with high levels of Medicare patients convinced Congress that they deserved a different rate of payment from other hospitals. Now, prospects are dimming for urban and other hospitals seeking a special funding increase for their high Medicare patient loads. The Prospective Payment Assessment Commission has advised Congress that special treatment should not be granted until further study has been completed. This article looks at both sides of the debate and gives a statistical picture of Medicare-dependent hospitals. PMID- 2190905 TI - CEO keeps high public profile. PMID- 2190906 TI - Counselor humanizes hospital for dying patients' families. PMID- 2190907 TI - Innovation marks career of retiring RWJF (Robert Wood Johnson Foundation) president. PMID- 2190908 TI - Observation units hold promise for outpatient care. PMID- 2190909 TI - The area of cancer in transurethral resection specimens as a prognostic indicator in carcinoma of the prostate: a computer-assisted morphometric study. AB - We used a computerized interactive morphometric method to determine total area of tissue and total area of cancer in routinely stained sections from each of 79 cases of prostatic adenocarcinoma, diagnosed by transurethral resection (TURP). The ability of two morphometrically determined parameters (area of cancer and percent area of cancer) to predict survival was compared with results obtained from two estimates of tumor area commonly used in clinical practice (number of chips and percent of chips involved by cancer). Total Gleason score was also determined. All patients were diagnosed prior to 1981, allowing follow-up of at least 5 years, or until death. Using the Cox proportional hazards regression analysis, our two morphometrically determined parameters, as well as the percentage of chips involved by cancer and total Gleason score, were significant predictors of survival. In contrast, the total number of chips involved by cancer did not reach statistical significance as a predictive factor for survival. By using our morphometrically determined area measurements as a bench mark for clinical utility of area estimates of cancer in TURP specimens, we concluded that calculating the percentage of involved chips yields prognostic information that closely approaches the "ideal" of these more time-consuming computer-assisted techniques. PMID- 2190910 TI - Neuropathologic findings after bone marrow transplantation: an autopsy study. AB - Clinicopathologic records and neuropathologic tissues of 109 patients who underwent necropsy after treatment with bone marrow transplantation (BMT) were examined. Underlying disorders included leukemia (70), aplastic anemia (25), solid tumors (7), lymphoma (5), Hodgkin's disease (1) and Wiskott-Aldrich syndrome (1). There were 34 females and 75 males, ranging in age from 2 to 56 years. Survival after transplantation averaged 3.6 months. The most common findings were cerebrovascular lesions (29), including hematomas, hemorrhagic necrosis, and infarcts. Central nervous system infections comprised the next most common finding, including 10 fungal and four bacterial infections. A recurrence of underlying malignancy for which transplant had been performed occurred in five patients. Leukoencephalopathy of varying severity was found in eight patients, half of whom had received intrathecal chemotherapy and/or cranial radiation. Patients with systemic graft-versus-host disease had a variety of nonspecific neuropathologic findings in the nervous system; however, nearly half (44%) showed no detectable changes. Other nonspecific alterations included hypoxic/ischemic changes, vascular siderocalcinosis, and neuroaxonal spheroids (associated with hemorrhage or necrosis). These findings provide a guide as to likely causes of a neurologic syndrome in a patient who has undergone BMT, and can be compared with neuropathologic findings in other forms of immunosuppression. PMID- 2190911 TI - Metachronous soft-tissue masses in children and young adults with cancer: correlation of histology and aspiration cytology. AB - We describe a series of 28 fine needle aspiration biopsies (FNAB) of soft tissue from 22 patients. Four patients had two separate FNABs, and one had three aspiration procedures. The patient population was limited to children and young adults (age range, 2 months to 29 years; mean, 16 years) who were known to have diverse forms of cancer, and who subsequently developed a mass in the peripheral soft tissues (including breast). The interval between the time of diagnosis of the primary malignant neoplasm and FNAB ranged from 1 day to 17 years (mean, 39 months). All FNAB diagnoses were confirmed by subsequent surgical open biopsy or clinical follow-up greater than 1 year. No complications occurred from the procedure. The cytomorphology is presented in selected cases and correlated with the patient's original tissue histopathology. Twenty aspirates were diagnosed as cytologically malignant, one as suspicious for malignancy. Seven were considered benign. None were unsatisfactory. One false-positive and no false-negative cytologic diagnoses were obtained. The overall accuracy of FNAB diagnoses was 96%, while sensitivity was 100% and specificity 88%. Sites of aspiration included soft tissues of the head and neck (seven cases), trunk (eight cases), breast (four cases), and extremities (nine cases). Malignant cytologic diagnoses included sarcoma (thirteen), seminoma (two), lymphoma/leukemia (two), melanoma (one), undifferentiated neoplasm (one), and neuroblastoma (one). Electron microscopy of aspirated cells was used to confirm the diagnosis in two cases. Fine needle aspiration biopsy of soft tissue masses from children and young adults with cancer demonstrates a high diagnostic accuracy, and its use is justified in this population. PMID- 2190912 TI - Intravenous streptokinase in acute evolving myocardial infarction--six to thirty six months follow up. AB - 270 consecutive patients who presented within six hours of the onset of acute myocardial infarction (AMI) and had no contraindication to thrombolytic therapy received intravenous infusion of 750,000 units of streptokinase (STK) in thirty minutes followed by heparin and oral anticoagulants. Treatment was instituted within 210 +/- 64 minutes after the onset of symptoms and reperfusion was achieved in 44 +/- 21 minutes. Reperfusion was recognised by indirect criteria in 249 patients, (92.2%) in the 0-6 hours group and 100% in the 0-3 hours group in all 72 patients. 2D echo LV ejection fraction (LVEF) improved from 51.6% +/- 9.4% at 0 hours to 60.61 +/- 8.4% at first week. In 40 patients (14.8%) there was early reocclusion in mean time of 36 +/- 13 hours of treatment. The incidence of reocclusion was higher in patients with anterior wall AMI than with inferior wall AMI. Reocclusion was also more frequent in patients who were administered adjuvant Dipyridamole therapy. In 36 of these patients reperfusion was achieved with an additional dose of streptokinase. During the last thirty-six months follow up, treadmill stress test was positive in 15 out of 80 (18.8%) streptokinase group subjected to it as compared to 42.2% conventionally managed patients. No LV thrombus, aneurysm or papillary muscle dysfunction was seen. 25 patients (9.2%) underwent coronary angiography six weeks later. CABG was undertaken in only 18 patients (6.6%) along with endarterectomy in one (.37%). None of the patients required additional aneurysmectomy or valve replacement. Elderly patients (above 75 years) suffered major haemorrhagic complications (.37%) and 17% of patients had minor bleeds. In-hospital mortality was 4.8% as compared to 10.2% in the control group (P less than .05). A long-term follow-up (6-36 months) revealed 11 patients that (4.07%) had reinfarction at mean time of 18 +/- 11 months (P less than .05). The late mortality rate in 6-36 months follow up was was 1.8% (P less than .05). It was concluded that intravenous streptokinase in acute myocardial infarction along with long-term anticoagulants is safe and effective. It reduces early and late mortality and morbidity significantly. A conservative strategy of subjecting patients to CABG after effective thrombolysis was found satisfactory during six to thirty-six months follow-up. PMID- 2190913 TI - Insulin administration reverses the metabolic and electrocardiographic changes in acute myocarditis induced by Indian red scorpion (Buthus tamulus) venom in experimental dogs. AB - Acute myocarditis was produced by injection of 4 mg/kg Indian red scorpion (Buthus tamulus) venom in dogs. Several rhythm changes, conduction defects, infarction-like pattern and many other ECG abnormalities; hyperglycemia, reduced insulin secretion, rise in free fatty acids along with fall in triglycerides; depletion of glycogen content of atria, ventricles, liver and skeletal muscles was noticed within 20-30 minutes after scorpion envenomation. Ten units of crystalline insulin was given i.v. at this time. All the arrhythmias, conduction defects and other ECG abnormalities disappeared after intervention with insulin. The sinus rhythm persisted for a duration of 120 minutes till the animals were sacrificed. Reduction in free fatty acids along with a rise in triglycerides; glycogenesis in liver, cardiac and skeletal muscles was observed at the time when ECG tracing was normal. It is suggested that catecholamines released during autonomic storm in scorpion poisoning suppress insulin secretion. These in turn result in glycogenolysis; lipolysis resulting in increased free fatty acids and produce arrhythmias. Insulin administration results in glycogenesis; lipogenesis and stops arrhythmias. PMID- 2190914 TI - [Listeria--a challenge for diagnosis]. AB - The isolation of Listeria spp. from polymicrobially contaminated materials from the environment of human beings is rather difficult. Suppression of the concomitant bacterial flora requires selective growth conditions. Different recipes have been reported to achieve this goal, whereby various antibiotics, among which cephalosporins and nalidixic acid, and dyes, such as acriflavin, have been proposed as supplements to suppress gram-positive as well as gram-negative bacteria. Cycloheximide may help to stop the growth of molds. The diversity of recommendations indicates, however, that an optimal selective medium has not yet been found. A possibility for selective enrichment is the cultivation in the cold, i.e. at +4 degrees C. In the future, genetic as well as immunologic methods will ameliorate the detection of Listeria spp. in environmental specimen. Actually, the offered test assays are still too insensitive so that they need a preceding enrichment process. The isolation of Listeria spp. from specimen of patients when they are present in pure culture is rather easy since these bacteria are not fastidious, so that they grow on the commonly used culture media. Sometimes it is difficult to differentiate Listeria spp. from other gram positive rods. For the sake of the evaluation of a cultural result it is advisable to characterize further the isolate by simple biochemical tests, since the seven known Listeria spp. among the genus Listeria differ quite definitely from each other in respect to their pathogenic potency. Only bacteria belonging to Listeria monocytogenes represent a potential risk for human health. PMID- 2190915 TI - [Diagnostic significance of neutrophilic cytoplasmic antibodies in nephrology]. AB - The existence of anti-neutrophil cytoplasm antibodies is helpful for differentiation and timely therapy of rapid progressive glomerulonephritis and the pulmonary renal syndrome. Various neutrophil cytoplasm immunofluorescence patterns are caused by antibodies against different antigens. PMID- 2190916 TI - Effect of steroids on ovarian neutral proteinases during ovulation in cyclic albino rats. AB - Progesterone (0.5 mg/rat) and estradiol-17 beta (10 micrograms/rat) injections (im) on the morning of proestrous in cyclic female rats enhanced the ovulation rate (number of ova shed). These steroids also significantly (P less than 0.05) increased the activity of ovarian neutral proteinases, observed on the morning of estrus as compared to those in control and vehicle treated animals. Nonsteroidal estrogen antagonist, tamoxifen suppressed ovulation rate and ovarian neutral proteinase activity as compared to control, its vehicle and steroidal treatment. The results demonstrate a stimulatory effect of progesterone and estradiol 17 beta on ovulation and ovarian neutral proteinases. PMID- 2190917 TI - Mutagenicity of systemic organophosphate pesticides metasystox and rogor. AB - Mutagenicity of metasystox and rogor could not be detected on the basis of tests employing Ames Salmonella/microsome assay even in the presence of wheat seedling or rat liver microsomal activation systems. PMID- 2190918 TI - 1989 Corcoran lecture: adaptive and maladaptive responses of the arterial wall to hypertension. AB - This study reviews recent experimental data from our own and other laboratories on the effects of hypertension on the arterial wall and the potential mechanisms by which hypertension can induce vascular injury and accelerate atherosclerosis. The findings suggest that the responses of the arterial media to hypertension reflect appropriate adaptations to increased intramural tension with resultant medial thickening secondary to an increase in both cellular mass and extracellular matrix. The role of growth factors in this process and their effects on arterial contractility are discussed as well as the potential importance of the changes in extracellular matrix constituents. The intimal changes induced by hypertension have many similarities to those caused by aging or hypercholesterolemia and can in part reflect general arterial responses to injury. They make the arterial wall more vulnerable to the effects of hypercholesterolemia, however, and as noted in our studies with the Watanabe heritable hyperlipidemic rabbit, pronounced acceleration of atherosclerosis is induced when hypertension is combined with hypercholesterolemia. Antihypertensive drugs can affect the arterial response to hypercholesterolemia. In the present study, new data are provided indicating that captopril inhibits aortic atherosclerosis in the Watanabe heritable hyperlipidemic rabbit in association with a pronounced reduction in cellularity of lesions. PMID- 2190919 TI - Hemodynamic differences between black patients and white patients with essential hypertension. State of the art lecture. AB - Physiological studies reported from our laboratory over the past several years have been reviewed and support epidemiological reports indicating that hypertensive cardiac and vascular disease runs a more severe course in the black patient. Although comparison of systemic hemodynamics failed to demonstrate that, for any level of arterial pressure, the magnitude of total peripheral resistance (which is the hemodynamic hallmark of hypertensive disease) differed between black patients and white patients, there are more subtle differences that were ascertained. Thus, although intravascular (plasma) volume contracts as arterial pressure and total peripheral resistance increase in both racial groups, this relation may differ quantitatively. At least in some black patients (43%), intravascular volume may be more expanded; in these patients, this relation is less closely correlated with the renopressor system (i.e., plasma renin activity). Moreover, these studies indicated that, at any level of arterial pressure, cardiac (left ventricular mass and posterior wall thickness) and renal hemodynamic involvement is more severe in the black patient. These findings point to important differences that operate in black patients and white patients with essential hypertension. With further study, these findings may be translated into more specific antihypertensive therapeutic implications for patients of both racial groups with essential hypertension. PMID- 2190920 TI - Differences in blacks and whites with essential hypertension: biochemistry and endocrine. State of the art lecture. AB - Overall, there is agreement that the origins of hypertension have a genetic basis. The genetic factors interact with environmental factors that influence expression and intensity of the disorder. As summarized in Table 1, there is evidence from the literature to identify pathways for the development of hypertension in blacks. Organ pathology, characteristic of the clinical phenotypic hypertension, consists of increased peripheral vascular resistance and left ventricular hypertrophy, and, particularly in blacks, nephrosclerosis. In this scheme, an intermediate phenotype is a biochemical or endocrine marker of gene expression that participates in the regulation of blood pressure. Intermediate phenotypic characteristics of essential hypertension include sodium sensitivity, adrenergic activity, cation transport, and endocrine function including renin-angiotensin-aldosterone, kallikrein-kinin, and prostaglandin. Another intermediate phenotype to be included in this discussion is insulin resistance. These intermediate phenotypes of cell and subcellular function are regulated by candidate genes. Alternatively, an intermediate phenotype can be expressed in response to another intermediate phenotype. For example, sodium sensitivity could be mediated by the cation transport mechanism of Na,K-ATPase, or insulin resistance could be induced by an elevated level of adrenergic activity. Gene expression of the intermediate phenotype is also modulated by environmental factors such as dietary sodium, potassium, or calcium, and social stresses or patterns of physical activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190921 TI - [Ca2+], not diacylglycerol, is the primary regulator of sustained swine arterial smooth muscle contraction. AB - Sustained smooth muscle contraction has been proposed to be regulated by either 1) sustained increases in intracellular Ca2+ concentration [(Ca2+]i)-dependent myosin phosphorylation or 2) diacylglycerol-dependent protein kinase C activation. We measured diacylglycerol mass with the diacylglycerol kinase assay and myoplasmic [Ca2+] with aequorin in swine carotid medial smooth muscle. Sustained and significant increases in [Ca2+], myosin light chain phosphorylation, and isometric stress were observed with histamine or endothelin stimulation. Neither stimuli, however, induced significant increases in diacylglycerol mass. Relaxation of histamine-stimulated tissues was induced by removal of histamine or removal of extracellular CaCl2 in the continued presence of histamine. The rate of decline of both [Ca2+] and force was similar in both protocols, suggesting that removal of Ca2+ (without removing the stimulus) was equivalent to removal of the stimulus. These data suggest that [Ca2+]i is the primary regulator of sustained swine arterial smooth muscle contraction, whereas diacylglycerol has, at most, only a minor role. PMID- 2190922 TI - Release of immunoreactive endothelin from porcine aortic strips. AB - The present study was designed to determine whether endothelin and "big endothelin" are released from aortic strips with endothelium and to examine the effect of thrombin by using a specific radioimmunoassay. Porcine aortic strips with endothelium released immunoreactive endothelin (ir-endothelin) and immunoreactive big endothelin (ir-big endothelin) into the medium in a time dependent manner. These releases were markedly inhibited by 10 micrograms/ml cycloheximide. Expectedly, after removal of endothelium, aortic strips did not release a detectable amount of ir-endothelin and ir-big endothelin. In contrast, thrombin (10 units/ml) significantly stimulated the release of ir-endothelin and ir-big endothelin. Reverse-phase high-performance liquid chromatography coupled with radioimmunoassay revealed that the major component of ir-endothelin corresponds to standard endothelin-1 (1-21) and the major component of ir-big endothelin corresponds to standard big endothelin (porcine, 1-39). These results suggest that aortic strips with endothelium release endothelin and big endothelin slowly but continuously into the extracellular space and that these releases can be stimulated by thrombin. PMID- 2190923 TI - Involvement of endothelin in renal processes. AB - This study examined the effect of various doses of endothelin (from 0.2 to 2 nmol/kg body wt) on regional hemodynamics in conscious unrestrained rats. Normal rats were instrumented chronically with femoral artery and vein catheters and pulsed Doppler flow probes simultaneously on the renal and superior mesenteric arteries and the abdominal aorta. Endothelin induced a biphasic response of mean arterial pressure. First, endothelin provoked a sharp hypotension with tachycardia, vasodilation of the hindquarter, and a pronounced decrease in renal and mesenteric blood flows. After this initial response, endothelin induced a dose-dependent increase of mean arterial pressure. Changes in the hindquarter vascular resistance were less pronounced than those in renal and mesenteric vascular resistances. Endothelin (2 nmol/kg) reduced renal flow (-86%) resulting from a vasoconstriction (+1,818%) significantly more pronounced than for the mesenteric vascular bed. In another set of experiments, endothelin (2 nmol/kg) induced an increase in proteinuria, characterized by an increase in excreted albumin and by the appearance of proteins with molecular weights of 20,000 280,000. Renal vascular bed exhibited a pronounced sensitivity to the vasoconstrictive effect of endothelin associated with changes in renal function. PMID- 2190924 TI - Chronic hypertension produced by infusion of endothelin in rats. AB - Endothelin, a potent vasoconstrictor peptide synthesized by the vascular smooth muscle endothelium, was chronically infused into male Sprague-Dawley rats to determine whether a long-term increase in circulating endothelin levels would cause a sustained elevation in mean arterial pressure. Rats were catheterized, housed in metabolic cages, and maintained on a fixed 6 meq/day sodium intake throughout the experiment with daily measurements including mean arterial pressure, heart rate, water intake, urine output, urinary sodium excretion, urinary potassium excretion, cardiac output, total peripheral resistance, and stroke volume. Infusion of endothelin-1 (ET-1) at rates of 3, 5, or 7.5 pmol/kg/min for 7 days was associated with significant, sustained, and dose dependent increases in mean arterial pressure and smaller less consistent elevations in total peripheral resistance. Other parameters were unaffected. Similar results were observed in rats receiving endothelin-3 (ET-3), except that a higher dose of ET-3 was required. These results indicate that elevated blood levels of endothelin could produce a maintained hypertension without sodium or water retention and that the hemodynamic basis for the increased mean arterial pressure is similar to that seen in most other forms of experimental and clinical hypertension. PMID- 2190925 TI - Application of monoclonal antibodies for endothelin to hypertensive research. AB - We developed six kinds of monoclonal antibodies against endothelin (ET)-1 recognizing different epitopes with high affinities (5 x 10(10) M-1 to 5 x 10(11) M-1). Using these monoclonal antibodies, we developed radioimmunoassays for ET-1 with different specificities. Cross-reactivities with ET-2 ranged from 80% to 100%, and those with ET-3 ranged from 3% to 60%. Patients with essential hypertension (n = 20) showed a significant elevation in the plasma ET-1-LI level compared with age-matched control subjects (n = 12) (30.1 +/- 1.4 pg/ml versus 18.5 +/- 0.9 pg/ml, p less than 0.01). The plasma ET-1-LI level in hypertensive patients in stages II and III (World Health Organization classification) was significantly higher than that in those patients in stage I. There was no significant correlation between the plasma ET-1-LI level and systolic blood pressure (r = 0.11), diastolic blood pressure (r = -0.13), or age (r = 0.24) in all patients studied who had essential hypertension. In the neutralization experiment, monoclonal antibodies attenuated ET-1-induced contraction of rat aortic rings and the pressor action of ET-1 in pithed rats in vivo. The present study demonstrates the elevated plasma ET-1-LI level in patients with essential hypertension. Monoclonal antibodies developed in this study can become powerful tools to investigate the pathophysiological significance of ET in essential hypertension. PMID- 2190926 TI - Effects of endothelin on neuroeffector junction in mesenteric arteries of hypertensive rats. AB - The effect of endothelin, a novel vasoconstrictor peptide, on the adrenergic neuroeffector junction was investigated in isolated perfused mesenteric arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. The vasoconstrictor responses to periarterial sympathetic nerve stimulation and exogenous norepinephrine were determined. Infusion of endothelin-1 increased the baseline perfusion pressure dose dependently to similar extents in the two strains. A subpressor dose of endothelin-1 (10(-10) M) enhanced the pressor response to norepinephrine; its effect was greater in WKY rats than in SHR. Endothelin-1 (10(-12) to 10(-10) M) attenuated the pressor response to sympathetic nerve stimulation, and the degree of inhibition tended to be less in SHR than in WKY rats. Higher doses (3 x 10(-10) and 10(-9) M) of endothelin-1 enhanced the pressor response to nerve stimulation in both WKY rats and SHR. Endothelin-1 inhibited norepinephrine release from rat mesenteric arteries; the inhibition was significantly less in SHR than in WKY rats. These results suggest that endothelin enhances the responsiveness of alpha-adrenergic receptors to catecholamines, whereas it inhibits presynaptic adrenergic neurotransmission. Thus, endothelin can interact with the neuroeffector junction in addition to having a vasoconstricting effect in peripheral vessels. The difference in the mode of modulation by endothelin at the vascular neuroeffector junction in SHR from that in WKY rats might explain the maintenance of hypertension. PMID- 2190927 TI - Prolonged duration of blood pressure response to enalkiren, the novel dipeptide renin inhibitor, in essential hypertension. AB - The effects of sustained renin inhibition by repeated administration of enalkiren (A-64662), the novel dipeptide renin inhibitor, were evaluated in a randomized, double-blind, placebo-controlled, parallel-group study of 32 inpatients (eight per group) with essential hypertension who were maintained on a diet containing 60 meq/day sodium. Three different dosage regimens of enalkiren were studied: 1) 1.2 mg/kg quotid., 2) 0.3 mg/kg q.i.d., and 3) 0.1 mg/kg q.i.d. Each patient received an intravenous infusion every 6 hours for 1 week. Placebo infusions were used to mimic the 4 times/day dosing schedule. Blood pressure was measured periodically via 24-hour automated monitoring equipment. Mean plasma renin activity in the patient groups ranged from 1.58 to 2.68 ng angiotensin I/ml/hr. Plasma renin activity was promptly suppressed in all groups receiving enalkiren. Prolonged duration of plasma renin activity suppression (greater than or equal to 24 hours) was demonstrated after the administration of 1.2 mg/kg enalkiren. The 0.3 mg/kg q.i.d. and 1.2 mg/kg quotid. regimens produced statistically significant reductions (p less than or equal to 0.05) in systolic and diastolic blood pressures with clear evidence of persistent antihypertensive activity for 12 hours or more when compared with the placebo group. Despite relatively large reductions in mean systolic and diastolic blood pressure, mean pulse rates were essentially unchanged. The prolonged reduction in blood pressure with enalkiren without evidence of tachyphylaxis after 1 week of treatment suggests that renin inhibitors may emerge as useful therapeutic agents for the treatment of hypertension. PMID- 2190928 TI - Central and peripheral actions of a nonpeptidic angiotensin II receptor antagonist. AB - Nonpeptidic imidazole derivatives were recently reported to be angiotensin II receptor antagonists with acute blood pressure-lowering activity. In the present study, we characterized the angiotensin II receptor antagonist properties of one such derivative, 4'-([2-butyl-4-chloro-5-(hydroxymethyl)-1H-imidazol-1-yl]methyl) [1,1'-biphenyl]-2-carboxylic acid (IMI). In receptor binding studies, IMI displaced bound [125I]angiotensin II from rat uterine membranes with an IC50 of 0.17 microM. In isolated rabbit aortic rings, IMI shifted the angiotensin II concentration-response curve to the right in a parallel and concentration dependent manner. A Schild plot of these data indicated a pA2 of 7.13 +/- 0.16 and a slope of 0.94 +/- 0.06. In rat kidney slices, IMI shifted the concentration response curve for angiotensin II-induced inhibition of renin release to the right. Antagonism of the angiotensin II pressor response by IMI was dose dependent and reversible in ganglion-blocked, anesthetized rats. The water intake and pressor responses to intracerebroventricular angiotensin II (100 pmol) were inhibited by intracerebroventricular IMI (25 or 50 nmol) in conscious Sprague Dawley rats. Similarly, the drinking and pressor responses to intravenous angiotensin II were blocked by intravenous IMI in conscious rats. IMI alone had no effects on mean arterial pressure or drinking when administered either intravenously or intracerebroventricularly. IMI decreased mean arterial pressure throughout 5 days of infusion in spontaneously hypertensive rats. In summary, IMI was a full competitive antagonist without partial agonist activity in peripheral tissues and the central nervous system. Moreover, the chronic administration of this angiotensin II receptor antagonist was antihypertensive in spontaneously hypertensive rats. PMID- 2190929 TI - Reninlike enzymes in human vasculature. AB - The present study was designed to identify angiotensin I (Ang I)-forming angiotensinogenases in human extrarenal vasculature and to examine the theory of Jimenez Dias on their stimulation in essential hypertension. Vascular sections obtained intraoperatively from 14 normotensive and 16 hypertensive patients undergoing corrective surgery, 68 umbilical cord blood vessels from parturient women, tissue samples from nine explanted hearts, and serum from anephric and healthy individuals were investigated. Ang I-forming angiotensinogenase activities were determined enzyme-kinetically by using Ang I radioimmunoassay and purified sheep or human angiotensinogens. Three nonrenin Ang I-forming angiotensinogenases (pH optima of 4.0, 5.1, and 6.1) were identified in extrarenal vasculature, in cardiac tissues, and in plasma. Highest specific activities of nonrenin Ang I-forming angiotensinogenase (in nanograms Ang I per gram times hour; mean +/- SD) were found in cardiac tissue (2,821 +/- 497, n = 9), followed by carotid artery intima (1,448 +/- 982, n = 10), arteries (1,307 +/ 736, n = 18), and umbilical cord arteries (135 +/- 55, n = 35). Extrarenal arterial Ang I-forming angiotensinogenases were linearly correlated with those of local angiotensin converting enzyme and plasma renin activity. In essential hypertension, extrarenal arterial Ang I-forming angiotensinogenases were scattered, but not generally stimulated. The data obtained indicate the existence of nonrenin Ang I-forming angiotensinogenases in human extrarenal vasculature, in kidney, and in plasma. The postulate of stimulation of extrarenal arterial Ang I forming angiotensinogenases in essential hypertension cannot be supported. Similar to the classification of plasma renin activity, a classification of Ang I forming angiotensinogenase activity is proposed, consisting of patients with essential hypertension divided into subgroups exhibiting high, normal, or low vascular Ang I-forming angiotensinogenase activities. PMID- 2190930 TI - Hyperinsulinemia and the aldosterone and pressor responses to angiotensin II. AB - To determine whether hyperinsulinemia alters angiotensin II-mediated aldosterone secretion, the increase in plasma aldosterone after intravenous angiotensin II (5, 10, and 20 ng/kg/min for 15 minutes each) was measured before and after euglycemic hyperinsulinemia in seven chronically instrumented dogs. In a random sequence on 4 successive days, dogs received either 0, 2, 4, or 8 milliunits/kg/min insulin. Euglycemic hyperinsulinemia, at all insulin doses, resulted in a significantly greater (p less than 0.01) change in the angiotensin II-stimulated increments of plasma aldosterone than was observed when angiotensin II was administered alone. However, there was no dose-dependence of insulin's effect on angiotensin II-stimulated aldosterone. The effect of weight gain on the angiotensin II response was also evaluated in five dogs. After weight gain, euglycemic hyperinsulinemia augmented angiotensin II-stimulated aldosterone to the same magnitude that was observed before weight gain. Possible mechanisms whereby insulin could increase angiotensin II-stimulated aldosterone production include: increased intracellular potassium, reduced plasma free fatty acids, and a direct action of insulin to induce increased adrenal steroidogenesis. In addition to altering the angiotensin II-aldosterone dose-response curve, hyperinsulinemia also increased the pressor action of angiotensin II. In contrast to the angiotensin II-aldosterone response, progressive hyperinsulinemia resulted in a progressive increase in the pressor response to angiotensin II. The increased pressor response is probably due to an increased activation of the sympathetic nervous system by insulin. PMID- 2190931 TI - Disseminated intravascular coagulation: diagnosis and current therapy. PMID- 2190932 TI - Desferrioxamine: its use in iron chelation in thalassemia. PMID- 2190933 TI - Antibiotic prophylaxis in proximal femoral fracture. AB - A prospective randomized double-blind trial was carried out to assess the effectiveness of one dose of prophylactic cefuroxime versus placebo in 502 patients who underwent surgery for a proximal femoral fracture. With an overall deep infection rate of 2.2 per cent there was no significant difference in the superficial or deep wound infection rate between the two groups. However, there was a significant reduction in the incidence of postoperative bacteriuria in the cefuroxime group. A study of three doses of cefuroxime versus placebo is now proposed. PMID- 2190934 TI - Intrathoracic migration of a Kirschner wire. AB - Migration of Kirschner wires, Rush pins, etc., is well known. Such migrations usually follow a retrograde path and the wires protrude near the entry point. Occasionally migration occurs in another direction. We describe a case in which the Kirschner wire migrated from the shoulder to the thorax. Several factors caused this migration. This complication must be avoided by bending the free end of the wire, removing the osteosynthesis material as soon as possible and following up the patient for a long period. PMID- 2190935 TI - Treatment of unstable intertrochanteric fractures of the femur: a prospective trial comparing anatomical reduction and valgus osteotomy. AB - A series of 100 consecutive patients with unstable intertrochanteric fractures were treated by compression hip screw fixation; 55 patients had an anatomical reduction (Group 1) and 45 patients a Sarmiento osteotomy and valgus reduction (Group 2). Group 1 spent an average of 10 days less in hospital than Group 2 (21 days compared with 31 days) (P less than 0.02). They also had a greater chance of returning to their pre-injury accommodation and of achieving their pre-injury walking capability. Radiological failure of fracture fixation, with varus angulation of the femoral head by cutting out of the screw, was seen seven times in Group 1 but only once in Group 2. Anatomical reduction provides better clinical results than valgus osteotomy in the patient with an unstable intertrochanteric fracture stabilized by a compression hip screw. The capacity for failure of fracture fixation is greater, however, in the former. Valgus osteotomy provides a simple means of securing a stable reduction of the fracture which cannot be satisfactorily reduced by closed means. PMID- 2190936 TI - A thorny problem: the diagnosis and treatment of acacia thorn injuries. AB - Immediate diagnosis and surgical treatment of acacia thorn injury results in complete cure. Delay or late presentation results in morbidity. The features of this disorder are presented in a series of 22 patients. The principles of treatment can be applied to all other types of thorn injury. PMID- 2190937 TI - Maintenance on extracellular matrix and expression of heparanase activity by human ovarian carcinoma cells from biopsy specimens. AB - A routine procedure has been developed for the isolation and maintenance in culture of human ovarian carcinoma cells derived from biopsy specimens. Cell attachment, plating efficiency and initial outgrowth were greatly improved by seeding the cells on a basement-membrane-like extracellular matrix (ECM) deposited by cultured corneal endothelial cells. These effects were most significant in serum-free conditions which markedly reduced the rate of cell attachment and growth on regular tissue culture plastic. In 60-80% of the cases and regardless of the patient's age, cells cultured on ECM in the absence of serum divided actively and formed a tightly packed epithelial cell monolayer. Fibroblast overgrowth and cell detachment often occurred on ECM in the presence of serum. Incubation of the human ovarian carcinoma cells with sulfate-labelled ECM, resulted in the release of heparan sulfate degradation fragments, 4- to 7 fold smaller than intact heparan sulfate side chains. This degradation was brought about by endoglycosidase (heparanase) activity expressed to a higher extent by cells that were first maintained in primary cultures as compared with cell aggregates taken directly from the biopsy specimen. In most cases, cells derived from metastatic tumors expressed a higher heparanase activity than cells from the primary ovarian tumor. This result corroborates previous studies, performed with cell lines, on the possible involvement of heparanase in tumor cell invasion and metastasis. PMID- 2190938 TI - Characterization of a 90-100 kDa tumor-associated antigen in the sera of melanoma patients. AB - Using allogeneic antibody, we previously described a high-molecular-weight glycoprotein in the urine of 68% of melanoma patients. This glycoprotein has been termed urinary-tumor-associated antigen (U-TAA). A murine monoclonal antibody (MAb) specific for U-TAA (ADI-40F4) has been developed. By the use of ADI-40F4, U TAA was detected in serum samples from 63% (33/52) of stage II and stage III melanoma patients, but from only 5% (1/20) of normal controls. This report describes the physical and immunochemical properties of U-TAA in the serum. The antigen elutes from a DEAE-Sephacel column in association with IgG in the void volume and as free antigen in a second peak. The molecular mass of the free antigen is 590-620 kDa and it sediments in the region of 28-29% sucrose by density gradient ultracentrifugation. Free antigen has an isoelectric point of 6.1. This high molecular weight antigen is composed of smaller subunits linked by reducible bonds. The ADI-40F4 reactive epitope resides on a 90-100 kDa subunit. These results provide evidence that U-TAA which is produced by melanoma cells in vitro is present in the circulation of melanoma patients. PMID- 2190940 TI - The sialosyl Lewis a ganglioside is present in tumorigenic human urothelial cell lines. AB - The sialosyl Lewis a antigen was identified in a ganglioside extract from a malignant human urothelial cell line (Hu 1703He) by fast atom bombardment mass spectrometry. The presence of this antigen in urothelial cell lines with varying tumorigenic properties was further studied using the 19-9 monoclonal antibody (MAb). The sialosyl Lewis a ganglioside was expressed only in the tumorigenic cell lines. Thus, the expression of this antigen is a marker of malignancy for human urothelial cell lines. Mass spectrometry also suggests that the fucosyl GM1 ganglioside was expressed in the Hu 1703He cell line. This was confirmed using the F12 MAb, specific for fucosyl GM1. However, the expression of this antigen was not confined to cell lines with tumorigenic properties. PMID- 2190939 TI - Expression of ras oncogene leads to down-regulation of protein kinase C. AB - The effect of mutated c-Ha-ras expression on Ca2+ and phospholipid-dependent protein kinase C (PKC) activity during the process of transformation was analysed using an inducible metallothionein-ras hybrid oncogene system. A close correlation was found between the timing of ras expression and the loss of PKC enzymatic activity measured in a cell-free system. Examination of the subcellular distribution of the enzyme in inducible and constitutive ras-transformants revealed that expression of ras was associated with an apparent translocation of PKC to the plasma membrane concomitant with down-regulation of PKC enzymatic activity in particulate as well as cytosolic fractions. Quantitation of PKC protein utilizing a PKC-specific antiserum showed that ras expression was associated with a decrease in the total amount of PKC protein present in the cell. We conclude that transformation by c-Ha-ras is accompanied by down regulation of PKC activity and that the basis of this effect may, to a large extent, lie in the down-regulation of the amount of PKC protein. PMID- 2190941 TI - The Wolff-Parkinson-White syndrome in childhood. PMID- 2190942 TI - Case-control designs in the study of common diseases: updates on the demise of the rare disease assumption and the choice of sampling scheme for controls. AB - In recent years the use of case-control designs has been extended to the study of common diseases. It has been shown that the rare disease assumption is not necessary, and that by a suitable choice of sampling scheme for controls, it is possible to obtain direct estimates of relative risk and relative rate, instead of relying on the odds ratio as an indirect estimate. The majority of papers addressing these issues are theoretical, and the arguments have been couched in mathematical terms. As such they are not readily accessible to many practising epidemiologists. This paper summarizes the discussion in a simplified manner. It describes the three different measures of relative incidence, namely the relative risk, the relative rate and the odds ratio, together with their corresponding case-control designs. The discussion is extended to show that the choice of the appropriate measure of relative incidence depends on the mode of action of the risk factor, as well as on characteristics of disease. We propose a classification scheme comprising five different categories of situation, and make recommendations regarding study designs for each. PMID- 2190943 TI - Identifying the malnourished within Peru: regional variation in the performance of a nutrition indicator. AB - Malnourished children may also have siblings at increased risk of poor health. Early identification of siblings at risk could lead to timely intervention to prevent the development of malnutrition or other potentially life-threatening events. In a nationwide survey conducted in Peru in 1984, stunting in an older sibling (defined as height/age less than or equal to 3.00 SD of the NCHS/CDC reference median) was evaluated as an indicator for stunting in a target sibling (next youngest) sibling) (n = 3284). The prevalence of stunting was much higher in target siblings who had an older sibling with stunting compared to those whose older sibling was not stunted, with prevalence ratios of 8.5 in Lima, 4.7 in urban areas, and 2.5 in rural areas. Screening indices (sensitivity, specificity, and predictive value positive) also showed marked variation across regions. The variation in this indicator's performance across regions demonstrates the importance of evaluating screening tools within the populations where they will be applied. Regional variations in the performance of malnutrition indicators should be anticipated because malnutrition is the result of a complex, multifactorial process. PMID- 2190944 TI - Fertilization in teleost fishes: mechanisms of sperm-egg interactions. PMID- 2190945 TI - Protein secretion and secretory processes in male accessory sex glands. PMID- 2190946 TI - The inheritance of MS susceptibility. AB - The object of this study was to determine, if possible, the mode of inheritance of the susceptibility to multiple sclerosis (MS). It was known that no single gene model could fit the observations, so oligogenic models (models involving a small number of genes) were sought. Oligogenic hypotheses were tested against the available population data for MS until a reasonable level of agreement was found. The best-fitting simple hypothesis was this: MS occurs only in people who are homozygous for a recessive gene and carry a dominant X gene, and then only with reduced penetrance. The dangerous allele m- at the autosomal locus appears to be fairly uniformly distributed across England, Ireland and Canada, occurring in 10 30% of the gene pool. There are large variations in the frequency of the allele s at the X-locus, ranging from 10% up to 72% of the gene pool. The penetrance varies significantly with geographical location, but nowhere approaches unity, so that the environmental factors are of great importance. The hypothesis explains the broad features of the population pattern of the occurrence of MS and it gives an outstanding fit to the best available data on MS in relatives. The result may assist attempts to map the genetic data on MS, opens the way for a reassessment of the attempts to identify the environmental factors, and it makes possible the completion of nonempirical risk tables for various countries. Similar techniques may be applied to other disorders with a genetic component in their aetiology. PMID- 2190947 TI - Inhibition of chemotactic migration of human neutrophilic granulocytes by recombinant human granulocyte-macrophage colony-stimulating factor. AB - Human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) was analysed for effects on the migration of human neutrophilic granulocytes by the Boyden chamber assay. At concentrations ranging from 0.1 to 10,000 U/ml (or 10( 12) to 10-mol/l) GM-CSF had neither chemokinetic nor chemotactic activity. When added to the cells in the upper compartment of the chamber GM-CSF dose dependently inhibited the chemotactic migration towards the tripeptide f-Met-Leu Phe and the complement split product C5a. Chemotaxis towards f-Met-Leu-Phe was inhibited more efficiently by GM-CSF than C5a-induced migration. PMID- 2190948 TI - Hospital alliances: cooperative strategy in a competitive environment. AB - The resource dependence perspective is used to describe the formation of hospital alliances. Characteristics of alliances and their various strategies and structures are discussed. A life cycle model provides a framework for viewing the development and growth of alliances. Several dimensions for assessing alliance performance are proposed. PMID- 2190949 TI - A strategic planning framework for endowment management. AB - New techniques in portfolio management can be used to integrate the management of long-term investments into implementation of the strategic plan. This integration requires cash-flow planning, portfolio restructuring, and continuous monitoring. PMID- 2190951 TI - DNA-induced distamycin A fluorescence. AB - The fluorescent properties of the antibiotic distamycin A were investigated in a range of materials including Trypanosoma cruzi epimastigotes, chicken erythrocytes, calf thymus DNA and synthetic polynucleotides using both microscopic and spectroscopic techniques. A bright blue-white fluorescence was observed from kinetoplast DNA and chromatin after treatment with distamycin A under ultraviolet (365 nm) excitation. Considerable enhancement of distamycin A fluorescence (emission peak at 455 nm under 320-340 nm excitation) was found in the presence of DNA and poly(dA-dT).poly(dA-dT). We discuss a possible explanation for this unexpected fluorescent emission, as well as its implications for microscopic and fluorimetric studies. PMID- 2190950 TI - Detection of DNA sequences in Plasmodium berghei by means of in situ hybridization. AB - A non-radioactive in situ hybridization technique, used to map unique DNA sequences to plant chromosomes, has been adapted for the localization of specific DNA sequences in nuclei of Plasmodium berghei. After hybridization using probes labeled with biotin-11-dUTP, the formed DNA/DNA hybrids were detected by fluorescence microscopy using a specific double-layer antibody technique. Besides its high resolution, this procedure is characterized by a high sensitivity, allowing the detection of a unique sequence as small as 2.5 kb. PMID- 2190953 TI - Immunology of xenograft rejection. PMID- 2190952 TI - Mechanisms of immunologic antitumor therapy: lessons from the laboratory and clinical applications. AB - The use of interleukin 2-based immunotherapies for cancer has been associated with significant responses in tumor models in both mouse and humans. Further definition of the elements responsible for response is now possible. It appears that the response is associated with T-cell infiltration of the tumor, and transfer of tumor-infiltrating lymphocytes expanded in tissue culture with interleukin 2 is associated with significant antitumor effects. Further expansion of cultured human melanoma tumor-infiltrating lymphocytes with suppression of lymphokine-activated killer activity as well as the modulation of monocyte activity by interleukin 4 suggests that this cytokine may be clinically useful alone or in combination with interleukin 2. Other means of enhancing the activity of interleukin 2-based immunotherapy are suggested by the finding that tumor cell susceptibility to lysis by natural killer cells is depressed following treatment with interferon gamma and tumor necrosis factor, but susceptibility to lysis by tumor-infiltrating lymphocytes is markedly enhanced. Further development of these therapies will require innovative interpretation and application of findings related to the processing and presentation of human tumor antigens and the nature of tumor antigens and careful analysis of the T-cell receptor in antitumor effectors. PMID- 2190954 TI - The potential roles of vascular endothelium in immune reactions. AB - Cell-mediated immune reactions are initiated and regulated by antigen specific CD4+ helper T cells. However, T cells cannot function independently. In order for a CD4+ T cell to recognize antigen, it must be presented in association with a class II major histocompatibility complex molecule by another cell type and, in order to lead to functional T-cell activation, the antigen presenting cell must also provide costimulatory signals. Once activated, CD4+ T cells function in vivo by secreting cytokines that elicit an inflammatory infiltrate of other cell types that serves to eliminate the source of foreign antigen. In vivo, the development of inflammation requires vascular responses as well as contributions of blood derived leukocytes. Although several cell types in vitro can present antigen, provide costimulation, and perform actions that contribute to inflammation, vascular endothelial cells may be uniquely important immune accessory cells because they are anatomically uniquely positioned to function in vivo during cell mediated immune reactions. In this report, we shall review recent data from our laboratories which further characterize the immune accessory functions of endothelial cells. PMID- 2190955 TI - Reconsideration of the mechanism of first-set vascularized allograft rejection: some concluding remarks. PMID- 2190956 TI - T-cell receptor gene usage and expression in renal allograft-derived T-cell lines. AB - Southern blot analyses indicate that the T-cell receptors of alloreactive T-cell lines derived from needle biopsies of human kidney allografts are selected based on beta-chain usage. In order to examine this selection at the level of T-cell receptor expression, we have generated monoclonal antibodies directed toward the T-cell-receptors of three allograft-derived T-cell lines, MH3, WP3, and EH3. Monoclonal antibodies have been isolated which appear to react specifically with each of these three T-cell lines. One anti-MH3 antibody precipitates a molecule from the surface of MH3 cells that comigrates with the alpha/beta TcR on a polyacrylamide gel. Ten WP3-reactive monoclonal antibodies were identified which cause a modulation of CD3 from the surface of WP3 T cells, although none as yet precipitates a molecule from lysates of surface 125I-labeled WP3 cells. Since Northern blot analysis of EH3 RNA has revealed that a member of the V beta 6 gene family is expressed by this T-cell line, we are attempting to identify a monoclonal antibody reactive with this V beta 6 gene product. PMID- 2190957 TI - Risk factors of nosocomial bacteremia associated with pulmonary artery catheters in a critical care unit. AB - An epidemiologic investigation at a community teaching hospital identified 17 cases of endemic primary nosocomial bacteremias associated with the use of pulmonary artery catheters (PACs). A matched-case control study was undertaken to identify risk factors associated with these bacteremias. Factors significantly associated with bacteremia were length of hospitalization; length of stay in the critical care unit; length of time the PAC introducer was left in place and used as an intravenous (IV) access device after PAC withdrawal; respiratory compromise; PAC site infection; prior infections at other sites; concomitant hyperalimentation; and number of IV piggyback administrations per day prior to onset of bacteremia. Pathogens isolated included coagulase-negative Staphylococcus species (55.6%), Staphylococcus aureus (22.2%), Candida albicans (14.8%), and enterococci (7.4%). These pathogens were generally resistant to antibiotics given before the development of bacteremia. Bacteremia was associated with significant mortality, a prolonged hospital stay, and increased hospital charges. This study identifies important risk factors to consider in formulating guidelines to prevent and control PAC-associated nosocomial infections. PMID- 2190958 TI - Psychiatric aspects of chronic disease in adolescence. AB - In adolescents with chronic illnesses, the rate of behavioral disorders is 10% to 20% higher than that in their well peers. Rheumatoid arthritis, chronic renal disease, cystic fibrosis, cancer, and many other chronic illnesses constitute risk factors for behavioral disorders in adolescents. Because they are now living longer, more productive lives, adolescents with chronic illnesses are more often seen by their primary care physicians with behavioral disorders that can interfere with disease control. Risk-taking behaviors, difficulties with parents, noncompliance, depression, and isolation may all be manifestations of behavioral disorders. Parents and siblings may also be at risk for disorder. Particular constellations of family and individual characteristics may be associated with behavior disorder. So that these behaviors may be discovered as early as possible, it is important that the primary care physician conceptualize chronically ill adolescents and their families as "at risk." PMID- 2190959 TI - A lifetime serving the dairy industry. PMID- 2190960 TI - Use of ultrasonographic and nuclear imaging to diagnose scrotal hernia in a dog. AB - Ultrasonography and nuclear imaging were used in the diagnosis of scrotal hernia in a dog. Both techniques were useful as aids in the differential diagnosis of scrotal enlargement. Nuclear imaging was useful in ruling out testicular torsion; ultrasonography revealed a normal-appearing testis amid fluid and portions of omentum. PMID- 2190961 TI - Ultrasonographic findings in horses with cholelithiasis: eight cases (1985-1987). AB - Cholelithiasis and/or obstructive biliary tract disease was diagnosed ultrasonographically in 8 horses, 5 to 15 years old. Ultrasonographic findings revealed greater than normal amount of hepatic parenchyma in the right side of the abdomen in 8 horses and in the left side in 3 horses. The echogenicity of the liver was greater than normal, and thick distended bile ducts were seen in all horses. Choleliths were imaged ultrasonographically in 6 horses. Subsequently, postmortem findings in 6 horses revealed periportal and intralobular fibrosis, moderate bile duct dilatation, proliferation, and cholestasis. One or more choleliths were found in all horses. Ultrasonographic findings accurately depicted the histologic changes in the hepatic parenchyma in horses with cholelithiasis. PMID- 2190962 TI - Drug therapy in cats: recommended dosing regimens. AB - The goal of this series of articles has been to provide a comprehensive review of the literature regarding recommended dosing regimens, therapeutic indications and contraindications, and potential side effects of drugs used in cats. In this fourth and last article, the available information regarding dosage regimens in cats has been consolidated in tabular form to facilitate an effective and rational approach to the pharmacologic prevention and treatment of a variety of feline medical disorders. PMID- 2190963 TI - Risks associated with use of live vaccines. PMID- 2190964 TI - The mode of antifungal action of (S)2-amino-4-oxo-5-hydroxypentanoic acid, RI 331. AB - An antifungal amino acid antibiotic, (S)2-amino-4-oxo-5-hydroxypentanoic acid (RI 331) isolated from Streptomyces sp., inhibited the biosynthesis of protein to a greater extent than that of RNA or DNA in growing Saccharomyces cerevisiae cells. Polypeptide biosynthesis in a cell-free system from the yeast was refractory to the antibiotic, suggesting the possibility that the biosynthesis of one or more amino acids might be inhibited. Intracellular amino acid pools, particularly those of methionine, isoleucine and threonine were significantly reduced when yeast cells were incubated in the presence of RI-331. Consistent with this, the growth-inhibitory activity of RI-331 was markedly reversed by the addition of these amino acids into the growth medium, and an even greater effect was exerted by homoserine which works as a common metabolic precursor for these amino acids in yeasts. It looks likely therefore that the inhibition of biosyntheses of some or all of these amino acids by RI-331 is primarily responsible for overall inhibition of protein biosynthesis in yeasts, ultimately leading to cytostasis. This possible mechanism of RI-331 action appears to explain favorably the selective toxicity of the antibiotic against yeasts, since mammalians lack enzymatic systems for synthesizing methionine, isoleucine and threonine which are required as essential amino acids for growth. PMID- 2190965 TI - Techniques used for the determination of antimicrobial resistance and sensitivity in bacteria. Antimicrobial Agents Research Group. PMID- 2190966 TI - Survival of genetically engineered Escherichia coli in natural soil and river water. AB - Twelve derivatives of Escherichia coli strain HB101 which contained different sizes of plasmids ranging from 3.9 Kb to 48 Kb and encoding resistance to various antibiotics were used. When these organisms were introduced into natural river water, the population declined rapidly and by day 3, the majority (i.e. more than 99.9%) of them could no longer be detected on antibiotic-amended culture plates. If the river water was filter sterilized first, the added organisms maintained their population for up to 7 d without any significant decrease in numbers. Similar results were also observed in sterilized tap water or distilled water. This indicated that the disappearance of these organisms in the aquatic environment was caused mainly by biotic factor(s). The loss of the ability to grow in the presence of antibiotics by some of the E. coli was not observed unless they were allowed to grow in the antibiotic-free environment first. When the test organisms were added to natural silt loam, a large portion of the original population still remained viable after 16 d. There was no relationship between the percentage survival of E. coli in natural river water and the sizes of plasmid harboured. On the other hand, when these bacteria were added to natural soil, survival appeared to increase as plasmid size increased. PMID- 2190967 TI - Coliforms as a measure of sewage contamination of the River Zambezi. AB - The effect of releasing untreated sewage from Victoria Falls Town into the Zambezi river was determined by bacteriological examination of water samples collected upstream of Victoria Falls and for 22 km downstream. Most probable numbers of faecal coliforms and Escherichia coli were estimated. Water upstream of the falls, on the Zimbabwe side of the river, contained between seven and 130 E. coli per 100 ml. This section of the river was free from major sources of faecal pollution. Below the falls, but before the Victoria Falls Town sewage outfall, numbers of E. coli were between 1.8 X 10(2) and 1.4 X 10(4)/100 ml, indicating the existence of a sewage discharge other than that from Victoria Falls Town. The river was also highly polluted from the Victoria Falls Town sewage outfall to a point 18.6 km downstream. The highest E. coli count was 3.3 X 10(4)/100 ml and declined slowly to 1.4 X 10(3)/100 ml 18.6 km downstream of the outfall. PMID- 2190968 TI - Prophylactic antibiotics for recurrent urinary tract infections. PMID- 2190969 TI - Susceptibility of bacterial biofilms to tobramycin: role of specific growth rate and phase in the division cycle. AB - A novel method of cell culture, enabling growth rate control of sessile Gram negative populations, has been employed to assess the sensitivity of Escherichia coli towards the aminoglycoside antibiotic, tobramycin. Changes in sensitivity, dependent on the growth rate, were compared with those for suspended populations grown in a chemostat and also those for newly-formed daughter cells shed from the biofilm during its growth and development. At specific growth rates up to 0.3 h-1 the susceptibility both of the resuspended biofilm cells and of their planktonic, chemostat grown controls increased in proportion to the growth rate. As the growth rate was increased further (up to 0.7h-1), the susceptibility of the resuspended biofilm cells remained high, whilst that of the planktonic controls decreased. Newly-formed daughter cells, dislodged from the biofilm, demonstrated a uniformly high sensitivity to the antibiotic at all growth rates. This sensitivity corresponded to that of the fastest-growing cells resuspended from biofilms. Lack of growth rate dependency of killing for the newly-formed daughter cells and their high sensitivity to tobramycin suggested that tobramycin activity might vary during the cellular division cycle. Indeed, when synchronous populations were exposed to tobramycin at various times during their division cycle, sensitivity decreased markedly 20 min before the onset of septation, and increased as septation began. Regulation of the cellular division cycle might therefore account, at least partly, for the observed effects of growth rate on susceptibility. PMID- 2190970 TI - Biotinylated probes for epidemiological studies of drug resistance in Salmonella krefeld. AB - A gene probe for ampicillin resistance and one for sulphonamide resistance were prepared to study the origin and the relation of multiple drug resistances in Salmonella krefeld. The resistance genes were cloned into the pACYC184 vector of Escherichia coli from a common plasmid of S. krefeld that encoded for resistance to ampicillin, chloramphenicol, kanamycin, streptomycin, sulphonamide and tetracycline resistance. Restriction map analysis and deletion analysis of a recombinant plasmid (pACSS1) showed that the gene determining ampicillin resistance was located on a 1.34 and 1.12 kb PstI fragment, and that the gene for sulphonamide resistance was located on a 0.85 kb PstI fragment. These fragments were used as probes. Their specificity was tested by colony hybridization with various bacterial species, including sensitive and resistance S. krefeld isolates. Further study indicated that the ampicillin resistance gene probe reacted with the gene for TEM-1 beta-lactamase and that the gene probe for sulphonamide resistance reacted with the gene for type II dihydropteroate synthase. The two probes were sufficiently specific to allow study of the epidemiology of resistance in S. krefeld and other enteric bacteria. PMID- 2190971 TI - Relevance of the inoculum effect of antibiotics in the outcome of experimental infections caused by Escherichia coli. AB - The minimum dosage of antibiotics that reduced mortality in bacteraemic rats inoculated with two different Escherichia coli isolates was determined in an attempt to study the therapeutic importance of the inoculum effect. Low mortality rates (0-5%) at 48 h were obtained when antibiotics with minimal or no inoculum effect (ampicillin, cefuroxime, cefoxitin and gentamicin) were administered to yield serum levels 5 to 14 times the MIC, while antibiotics with a pronounced inoculum effect (piperacillin, cefotaxime and aztreonam) had to be administered to yield serum levels 57 to more than 1000 times the MIC determined with a standard (low) inoculum. All of the antibiotics with inoculum effect studied here are administered empirically in clinical practice at a higher dose than the microbiological and pharmacokinetic data would indicate (in order to reach peak serum concentrations exceeding the MICs of the pathogens by 4-10 times). Our experiment suggests that such high and empirical doses of antibiotics with inoculum effect may be justified. PMID- 2190972 TI - Treatment of experimental Salmonella typhimurium infection in mice with lomefloxacin. AB - To evaluate the difluorinated quinolone lomefloxacin in murine typhoid, mice were inoculated intraperitoneally with the LT-2 strain of Salmonella typhimurium and treated with graded doses of the drug given once daily by an orogastric needle. Treatment with lomefloxacin for seven days reduced mortality with a 50% effective dose of 2.5-7.8 mg/kg/day. When given once daily for three days, doses greater than or equal to 5 mg lomefloxacin/kg/day caused significant reductions in splenic counts of S. typhimurium and prevented the inflammatory response to infection in the spleen. PMID- 2190973 TI - Serum gentamicin assay: an assessment of two different Syva EMIT and Abbot TDx instruments. AB - The accuracy and reproducibility of two different Syva EMIT and Abbot TDx instruments for the determination of gentamicin were assessed. A series of spiked standard serum samples containing gentamicin in concentrations ranging from 0.88 17.82 mg/l were used for this purpose. Both TDx systems evaluated had excellent reproducibility but overestimated gentamicin levels in the clinically important concentration range in an apparent concentration-dependent way by at least 5 and 10%, respectively. In addition both these systems exhibited considerable carryover effects when high concentration gentamicin samples (17.82 mg/l) were alternated with serum blanks. Average gentamicin levels determined by the EMIT systems were much closer to the target values, especially those of EMIT-A, than those measured by the TDx-systems. The reproducibility, as measured by the coefficient of variation (CV), of the semi-automated EMIT systems over the entire concentration range investigated was about half that of the TDx-systems. No carryover effects were observed with the two EMIT-systems. This study has shown that the accuracy and reproducibility of both assay methods vary considerably over the clinically important gentamicin concentration range. In addition there may be a large variation between instruments of the same system especially in the critical trough region for gentamicin. PMID- 2190974 TI - A comparison of aztreonam/metronidazole and cefotaxime/metronidazole in elective colorectal surgery: antimicrobial prophylaxis must include gram-positive cover. AB - Aztreonam/metronidazole and cefotaxime/metronidazole were compared in a prospective trial in 154 patients undergoing elective colorectal surgery. Three antibiotic doses were given over 16 hours. A significant excess of wound sepsis in the aztreonam group was seen (23/71 vs 9/70 chi 2 6.60; P less than 0.01). Sepsis was almost invariably due to Gram-positive organisms and, in particular, Staphylococcus aureus. PMID- 2190975 TI - Incidence of gallbladder lithiasis after ceftriaxone treatment. AB - Ceftriaxone has potent activity against a broad range of Gram-positive and Gram negative bacteria. While it is eliminated mainly by the kidney, 10-20% of the drug is eliminated in the bile and ceftriaxone salt precipitates have been described in the gallbladder of animals dosed with ceftriaxone. The purpose of the present study was to investigate the incidence of biliary lithiasis 6 and 12 months after treatment with ceftriaxone and to compare it with that in patients treated with amoxycillin/clavulanate. Biliary ultrasonography was performed at the start of treatment, at 6 months and at 12 months after the beginning of the study. One hundred patients were randomized and 74 were evaluable: 34 were given amoxycillin/clavulanate, 40 ceftriaxone. Gallbladder lithiasis developed in one patient 12 months after the amoxycillin/clavulanate treatment and in none in the ceftriaxone treatment arm. Biliary precipitate during ceftriaxone treatment was not looked for because this phenomenon was not known at the beginning of the study, but gallbladder precipitation that was seen in two patients given ceftriaxone during and at the end of treatment, respectively, resolved spontaneously. In conclusion, ceftriaxone treatment does not appear to lead to gallstone formation more often than an antibiotic that is not eliminated through the bile. PMID- 2190976 TI - Zidovudine-resistance in Salmonella typhimurium and Escherichia coli. PMID- 2190977 TI - Autobacteriography for evaluating in-vivo antimicrobial activity of oral antibiotics in experimentally infected mice. PMID- 2190978 TI - Erythromycin-resistant Streptococcus pyogenes. PMID- 2190979 TI - Characterization of the integration host factor binding site in the ilvPG1 promoter region of the ilvGMEDA operon of Escherichia coli. AB - The ilvGMEDA operon of Escherichia coli, which encodes four of the five enzyme activities required for the biosynthesis of isoleucine and valine, is preceded by tandem promoters ilvPG1 and ilvPG2 which are separated by 72 base pairs. While both of these promoters are transcriptionally active in vitro, only the operon proximal promoter, ilvPG2, is transcriptionally active in vivo, and upstream DNA sequences encoding the ilvPG1 promoter region enhance the in vivo transcriptional activity of the ilvPG2 promoter 60-fold. The binding of the integration host factor protein (IHF) to this upstream region (Tsui, P., and Freundlich, M. (1989) J. Mol. Biol. 203, 817-820) has been shown to repress transcription from the ilvPG1 promoter both in vivo and in vitro (Pereira, R. F., Ortuno, M. J., and Lawther, R. P. (1988) Nucleic Acids Res. 16, 5972-5989). Furthermore, E. coli strains deficient for IHF are compromised for isoleucine and valine biosynthesis (Friden, P., Voelkel, K., Sternglantz, R., and Freundlich, M. (1984) J. Mol. Biol. 172, 573-579). Therefore, in order to further understand this repressor/activator role of IHF, we have undertaken a detailed analysis of the interaction of IHF with the DNA sequences in the ilvPG1 promoter region. The results of hydroxyl radical footprinting, dimethyl sulfate protection, and ethylation interference experiments show that IHF binds to a target site that overlaps the ilvPG1 promoter region. The results of these experiments also demonstrate that IHF interacts primarily with the minor groove of the DNA helix and that the IHF target site in the ilvPG1 promoter region shares a high degree of DNA sequence identity with other high affinity IHF target sites involved in DNA replication and site-specific recombination. PMID- 2190980 TI - Purification of three related peripheral membrane proteins needed for vesicular transport. AB - We report conditions under which Golgi membranes depleted of peripheral membrane proteins can be reconstituted for intra-cisternal vesicular transport. Analysis of the reconstitution reveals requirements for N-ethylmaleimide-sensitive fusion protein, a purified peripheral protein involved in the fusion stage of vesicular transport, as well as other peripheral protein activities which can be provided by mammalian cytosol but not yeast cytosol. The restorative activity in bovine brain cytosol is found in two broad and complementing fractions, of average native molecular masses of about 500 and 40 kDa, termed Fr1 and Fr2, respectively. This resolved transport system was used to develop a purification scheme for Fr2. Three proteins of apparent molecular masses of 35, 36, and 39 kDa (Fr2-alpha, -beta, and -gamma, respectively) were found to be responsible for Fr2 activity and were purified to homogeneity. Each Fr2 protein has activity by itself in the reconstituted in vitro Golgi transport assay, although each exhibits a different specific activity and plateau value. No synergy of the three Fr2 proteins was observed during mixing experiments. The three Fr2 proteins seem to be closely related based on size, in vitro activities, chromatographic properties, and peptide maps and may comprise a new family of proteins involved in vesicular transport. PMID- 2190981 TI - On RecA protein-mediated homologous alignment of two DNA molecules. Three strands versus four strands. AB - The recA protein from Escherichia coli can homologously align two duplex DNA molecules; however, this interaction is much less efficient than the alignment of a single strand and a duplex. Three strand paranemic joints are readily detected. In contrast, duplex-duplex pairing is detected only when the incoming (second) duplex is negatively supercoiled, and even here the pairing is inefficient. The recA protein-promoted four strand exchange reaction is initiated in a three strand region, with efficiency increasing with the length of potential three strand pairing available for initiation. This indicates that a paranemic joint involving three DNA strands may be an important intermediate in all recA protein mediated DNA strand exchange reactions and that the presence of three strands rather than four is a fundamental structural parameter of paranemic joints. PMID- 2190982 TI - Primary structure of glycolipid transfer protein from pig brain. AB - The amino acid sequence of a glycolipid transfer protein from pig brain was determined by automatic sequencing and fast atom bombardment mass spectroscopic analysis of peptides produced by chemical and enzymatic cleavage reactions. The protein consists of 208 residues, with N-acetylalanine as the N-terminal residue and valine as the C-terminal residue. It contains 3 cysteine residues. The primary structure of the glycolipid transfer protein from pig brain is as follows: acetyl-A-L-L-A-E-H-L-L-K-P-L-P-A-D-K15-Q-I-E-T- G-P-F-L-E-A-V-S-H-L-P30 P-F-F-D-C-L-G-S-P-V-F- T-P-I-K45-A-D-I-S-G-N-I-T-K-I-K-A-V-Y-D60-T-N- P-A-K-F-R-T L-Q-N-I-L-E-V75-E-K-E-M-Y-G-A-E- W-P-K-V-G-A-T90-L-A-L-M-W-L-K-R-G-L-R-F-I-Q- V105-F-L-Q-S-I-C-D-G-E-R-D-E-N-H-P120-N-L-I-R- V-N-A-T-K-A-Y-E-M-A-L135-K-K-Y-H-G W-I-V-Q- K-I-F-Q-A-A150-L-Y-A-A-P-Y-K-S-D-F-L-K-A-L- S165-K-G-Q-N-V-T-E-E-E-C-L-E K-V-R180-L-F-L-V- N-Y-T-A-T-I-D-V-I-Y-E195-M-Y-T-K-M-N-A-E-L-N- Y-K-V-OH. The sequence does not have detectable homology with other lipid transfer proteins or lipid-binding proteins. The cysteine residue at position 35 is reactive to iodoacetamide under nondenaturing conditions. PMID- 2190983 TI - Identification of valine 177 as a mutation altering specificity for transport of sugars by the Escherichia coli lactose carrier. Enhanced specificity for sucrose and maltose. AB - A mutant of the Escherichia coli lactose carrier has been selected (in an invertase-positive strain) based on its ability to grow on 6 mM sucrose in a manner dependent upon lactose carrier induction by isopropyl-1-thio-beta-D galactopyranoside. The mutant was cloned, and DNA sequencing revealed a point mutation in lacY which changed alanine 177 to valine. The valine 177 mutation increased the transport rate for both [14C]sucrose and the maltose analog 4 nitrophenyl-alpha-maltoside. The potency for inhibition of beta-ONPG transport by several sugars containing the glucopyranosyl moiety (maltose, cellobiose, or palatinose) was increased significantly relative to the parental carrier. Similar experiments showed that the mutation did not affect the affinity for such commonly studied substrates as 4-nitrophenyl-alpha-D-galactopyranoside and beta-D galactopyranosyl-1-thio-beta-D-galactopyranoside. These data indicate that gross structural alteration of the galactoside binding site cannot account for increased transport of sucrose and maltose by the valine 177 mutant. We conclude that effects of the valine 177 mutation are not limited strictly to changes in observed sugar affinity and that sugar-specific changes in turnover number may be an important determinant of the altered spectrum of sugar specificities exhibited by the Val-177 carrier. These phenomena may be related to the effect of this mutation on proton recognition (described in King, S.C., and Wilson, T.H. (1990) J. Biol. Chem. 265, 9645-9651). PMID- 2190984 TI - Developmental regulation of glucosidase I, an enzyme involved in the processing of asparagine-linked glycoproteins in rat mammary gland. AB - Glucosidase I involved in the processing of N-linked glycoproteins was purified to homogeneity from the lactating rat mammary gland. The purified enzyme exhibited a single band at 85 kDa on 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. Polyclonal antibodies raised against the enzyme recognized a similar band on Western blots and also inhibited the enzyme activity. The enzyme levels gradually increased until the midlactation stage and thereafter declined sharply during the period of postlactation. A similar profile of the levels of immunoreactive glucosidase I was observed. These findings suggest that the accumulation of glucosidase I is modulated as a function of gland ontogeny. The results on hormonal regulation of glucosidase I indicate that the synthesis of the enzyme is stimulated by a combination of insulin, hydrocortisone, and prolactin; additionally, epidermal growth factor may play a role in this regulation. The above observation was substantiated by immunoprecipitation of [35S]methionine-labeled microsomal extracts with anti glucosidase I antibodies. The immunoprecipitation of soluble extracts from [35S]methionine-labeled tissue with anti-rat alpha-lactalbumin antibodies indicates that these hormones not only stimulate the synthesis of alpha lactalbumin but also play an important role in its glycosylation. PMID- 2190985 TI - The presence and distribution of reduced folates in Escherichia coli dihydrofolate reductase mutants. AB - Escherichia coli DNA photolyase was overproduced and purified from each of two mutant E. coli strains lacking dihydrofolate reductase. The extent of over production in the mutants was comparable to that seen in the wild type strain. Examination of the isolated photolyase from these strains revealed that the folate cofactor, 5,10-methenyltetrahydrofolate, was present in these proteins at a level of 60-80% compared to that purified from the wild type strain. Further examination of the dihydrofolate reductase-deficient strains revealed the presence of other tetrahydrofolate derivatives. These findings demonstrate that dihydrofolate reductase is not essential for the production of tetrahydrofolates in E. coli. PMID- 2190986 TI - Purification and characterization of rho-crystallin from Japanese common bullfrog lens. AB - In a previous paper, we reported that the partial amino acid sequence (225 residues) from the COOH terminus of rho-crystallin from European common frog lens shows 77% similarity to that of prostaglandin (PG) F synthetase, an aldo-keto reductase, from bovine lung (Watanabe, K., Fujii, Y., Nakayama, K., Ohkubo, H., Kuramitsu, S., Kagamiyama, H., Nakanishi, S., and Hayaishi, O. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 11-15). Here rho-crystallin was purified to apparent homogeneity from the eye lens of the Japanese common bullfrog (Rana catesbeiana) by four sequential chromatographies using Sephadex G-100, Red Sepharose, and dual Mono S. Two types of rho-crystallin, RHO-I and RHO-II, named according to their elution order from a Mono S column, are essentially identical in terms of immunochemical properties, amino acid composition, and partial amino acid sequence. But the NH2-terminal Thr of RHO-I is blocked with an acyl group, while that of RHO-II is free. Both crystallins as well as PGF synthetase are monomeric proteins with a molecular weight of about 35,000 and they have the ability to bind NADPH with a stoichiometry of 0.75 mol of cofactor/mol of protein. Although rho-crystallin does not cross-react with antibody against PGF synthetase, the NH2 terminal amino acid sequence (107 residues) of rho-crystallin shows 77% similarity to that of the enzyme. However, PGD2, PGE2, 9,10-phenanthrenequinone, p-nitrobenzaldehyde, DL-glyceraldehyde, D-glucuronic acid, D-glucose, D-xylose, menadione, p-nitroacetophenone, dihydroxyacetone, succinic semialdehyde, phenylglyoxal, and testosterone were not substrates for these crystallins. PGH2 9,11-endoperoxide reductase activities of RHO-I and RHO-II were 1.3 and 1.0 milliunits/mg of protein, respectively, which are only about 2% of that of bovine lung PGF synthetase. These results indicate that the rho-crystallins RHO-I and RHO-II belong to a group of aldo-keto reductases based on primary structure, molecular properties, and NADPH-binding ability, but show only low PGH2 9,11 endoperoxide reductase activity. PMID- 2190987 TI - Primary sequence and heterologous expression of nuclear pore glycoprotein p62. AB - The major nuclear pore protein p62 is modified by O-linked N-acetylglucosamine and functions in nuclear transport. We have cloned, sequenced, and expressed the full-length rat p62 cDNA. The rat p62 mRNA is 2,941 nucleotides long and encodes a protein of 525 amino acids containing 30% serine and threonine residues. The amino acid sequence near the amino-terminus contains unique tetrapeptide repeats while the carboxy-terminus consists of a series of predicted alpha-helical regions with hydrophobic heptad repeats. Heterologous expression of rat p62 in African Green Monkey Kidney COS-1 cells and CV-1 cells was detected using a species-specific antipeptide serum. When transiently expressed in COS-1 cells, rat p62 binds wheat germ agglutinin and concentrates at the spindle poles during mitosis. In CV-1 cells cotransfected with rat p62 cDNA and SV40 viral DNA, rat p62 associates with the nuclear membrane without interfering with the nuclear transport of SV40 large T antigen. The ability to express p62 in tissue culture cells will facilitate analysis of the role of this pore protein in nuclear transport. PMID- 2190988 TI - Loss of BiP/GRP78 function blocks translocation of secretory proteins in yeast. AB - BiP/GRP78 is an essential member of the HSP70 family that resides in the lumen of the endoplasmic reticulum. In yeast, BiP/GRP78 is encoded by the KAR2 gene. A temperature sensitive mutation was isolated in KAR2 and found to cause a rapid block in protein secretion. Secretory precursors of a number of proteins (invertase, carboxypeptidase Y, alpha-factor, and BiP) accumulated that were characteristic of a block in translocation into the lumen of the ER. Protease protection experiments confirmed that the precursors accumulated on the cytoplasmic side of the ER membrane. Moreover, depletion of wild-type KAR2 protein also resulted in a block in translocation of secretory proteins. These results implicate BiP/GRP78 function in the continued translocation of proteins into the lumen of the ER. PMID- 2190989 TI - Detection of an intermediate compartment involved in transport of alpha-factor from the plasma membrane to the vacuole in yeast. AB - alpha-Factor, one of the mating pheromones of Saccharomyces cerevisiae, binds specifically to a receptor on the plasma membrane of a cells, is internalized and delivered to the vacuole, where it is degraded. At 15 degrees C the rate of pheromone uptake is only slightly affected while delivery to the vacuole is markedly slowed down. A transport intermediate carrying alpha-factor to the vacuole can be reversibly trapped by treatment with the metabolic inhibitors, NaN3 and NaF. This intermediate(s) is distinct from the vacuole and the plasma membrane as judged by differential and density gradient centrifugation analysis. We present evidence that the alpha-factor is protected from protease digestion by a detergent-sensitive structure, suggesting that the pheromone resides within a vesicular compartment. We propose that this intermediate(s) represents an endocytic or prevacuolar compartment(s) involved in vesicular traffic from the plasma membrane to the vacuole. PMID- 2190990 TI - Centrosome duplication continues in cycloheximide-treated Xenopus blastulae in the absence of a detectable cell cycle. AB - Cycloheximide (500 micrograms/ml) rapidly arrests cleavage, spindle assembly, and cycles of an M-phase-specific histone kinase in early Xenopus blastulae. 2 h after cycloheximide addition, most cells contained two microtubule asters radiating from perinuclear microtubule organizing centers (MTOCs). In contrast, blastomeres treated with cycloheximide for longer periods (3-6 h) contained numerous microtubule asters and MTOCs. Immunofluorescence with an anticentrosome serum and EM demonstrated that the MTOCs in cycloheximide-treated cells were typical centrosomes, containing centrioles and pericentriolar material. We conclude that centrosome duplication continues in cycloheximide-treated Xenopus blastulae in the absence of a detectable cell cycle. In addition, these observations suggest that Xenopus embryos contain sufficient material to assemble 1,000-2,000 centrosomes in the absence of normal protein synthesis. PMID- 2190991 TI - Neuroblast mitosis in dissociated culture: regulation and relationship to differentiation. AB - Although neuron generation is precisely regulated during ontogeny, little is known about underlying mechanisms. In addition, relationships between precursor proliferation and the apparent sequence of developmental processes, including cell migration, neurite elaboration, transmitter expression and synaptogenesis remain unknown. To address these issues, we used a fully defined neuronal cell culture system derived from embryonic rat sympathetic ganglia (DiCicco-Bloom, E., and I. B. Black. 1988. Proc. Natl. Acad. Sci. USA. 85:4066-4070) in which precursors enter the mitotic cycle. We now find that, in addition to synthesizing DNA, neuroblasts also underwent division in culture, allowing analysis of developmental relationships and mitotic regulation. Our observations indicate that mitotic neuroblasts expressed a wide array of neuron-specific characteristics including extension of neuritic processes with growth cones, elaboration of neurotransmitter enzyme, synthesis and transport of transmitter vesicles and organization of transmitter release sites. These data suggest that neuroblasts in the cell cycle may simultaneously differentiate. Consequently, the apparent sequence of ontogenetic processes is not an immutable, intrinsic neuronal program. How, then, are diverse developmental events coordinated? Our observations indicate that neuroblast mitosis is regulated by a small number of epigenetic factors, including insulin and EGF. Since these signals also influence other processes in developing neurons, epigenetic regulation normally may synchronize diverse ontogenetic events. PMID- 2190993 TI - The early expression of myofibrillar proteins in round postmitotic myoblasts of embryonic skeletal muscle. AB - Previous reports on skeletal muscle myogenesis have shown that postmitotic spindle-shaped myoblasts express muscle-specific proteins, some of which are organized into nascent myofibrils. However, we show that, in skeletal muscle cultures derived from 12-day chick embryos, by 6 h after plating the predominant mononucleated cell type that expresses muscle-specific proteins is a round cell. These round myoblasts appear to precede spindle-shaped myoblasts in development, since the latter are more abundant in later cultures and contain larger amounts of muscle proteins and more highly organized myofibrils. By double immunofluorescence microscopy using antibodies specific for the muscle proteins titin, myosin heavy chain (MHC) and zeugmatin we find that 18 h after plating approximately 20% of the round myoblasts that are titin-positive are negative for myofibrillar MHC and zeugmatin. On the other hand, all spindle-shaped myocytes that are positive for titin are also positive for myofibrillar MHC and zeugmatin. These results suggest that titin expression precedes that of myofibrillar MHC and zeugmatin in the non-synchronized round myoblasts, and is consistent with earlier suggestions that titin may function as an initial organizer of myofibrillar proteins during myogenesis. Immunofluorescence data indicate that the earliest localization of the myofibrillar proteins titin, MHC, zeugmatin and alpha-actinin in the round myoblasts is surrounding the nucleus with no immunofluorescent labeling of the cytoplasm or near the plasma membrane. Furthermore, pairwise double immunofluorescence experiments show that these four myofibrillar proteins are all co-localized, at the light-microscopic level of resolution, in irregular patterns that may appear in either a punctate or a basket-like distribution. These labeling patterns around the nucleus are resistant to extraction with Triton X-100, suggesting that the proteins are associated in a stable array. These Triton X-100-resistant assemblies in round myoblasts appear to be composed solely of structural myofibrillar proteins, since the non-structural myofibrillar protein creatine kinase (CK) does not colocalize with the other myofibrillar proteins. These results indicate that in early myoblasts myofibrillar proteins form stable pre-myofibrillar assemblies surrounding the nucleus, and raise the possibility that these initial assemblies may play an organizing role during subsequent early stages of myofibrillogenesis. PMID- 2190994 TI - Control of fluid transport in human rectal adenocarcinoma cells (HRA-19) in monolayer and collagen gel cultures. AB - HRA-19a1.1. cells, derived from a primary human rectal adenocarcinoma, form polarised monolayers when grown on tissue-culture plastic. HRA-19 monolayers have a heterogeneous morphology even after 150 passages in vitro or single cell cloning. The morphological changes observed in HRA-19 monolayers were postulated to be the result of vectorial fluid transport leading to accumulation of fluid between cells. To test this hypothesis, a variety of agents that control ion transport in colorectal epithelium were tested for their effect on HRA-19 morphology. Forskolin, cholera toxin and prostaglandin E2 all markedly changed HRA-19 monolayer morphology, with the rapid disappearance of intercellular spaces. These agents all stimulate Cl- secretion in colorectal epithelium, i.e. transport from basolateral to apical surface, and therefore would be expected to reduce fluid accumulation at the basolateral side of the cell. Conversely, vasopressin, which stimulates absorption of Na+ and water across colorectal epithelium, leads to a small increase in intercellular spaces in the monolayer. In collagen gel cultures, addition of cholera toxin, forskolin or prostaglandin E2 resulted in a large increase in colony size. In such treated cultures, the colonies were 'bubble-like', often composed of a single rim of flattened cells, which appeared to encompass a fluid-filled space. Similar morphological changes were observed when HRA-19 cells were co-cultured with 3T3 cells. This effect was probably due, at least in part, to prostaglandin production by the 3T3 cells, as the effect could be markedly reduced by the addition of indomethacin to these cultures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2190992 TI - A homing receptor-IgG chimera as a probe for adhesive ligands of lymph node high endothelial venules. AB - The binding of lymphocytes to high endothelial venules (HEV) within peripheral lymph nodes (pln) is thought to be mediated by a lectinlike adhesion molecule termed the pln homing receptor (pln HR). The cloning and sequencing of cDNAs encoding both murine and human pln HR revealed that these adhesion molecules contain protein motifs that are homologous to C-type or calcium dependent lectin domains as well as to epidermal growth factor (egf) and complement-regulatory protein domains. We have produced a novel, antibody-like form of the murine HR by joining the extracellular region of the receptor to a human IgG heavy chain. This antibody-like molecule is capable of recognizing carbohydrates, blocking the binding of lymphocytes to pln HEV, and serving as a histochemical reagent for the staining of pln HEV. This murine HR-IgG chimera should prove useful in analyzing the distribution of the HR ligand(s) in normal as well as in inflammatory states. PMID- 2190995 TI - Interphase microtubule dynamics are cell type-specific. AB - The rate and pattern of microtubule polymer loss in interphase cells have been examined using nocodazole to block microtubule assembly. Cells were incubated with high concentrations of nocodazole for various times and the pattern of microtubule disassembly was determined using tubulin immunofluorescence. Polymer loss was quantitated by measuring the decrease in percentage of cell area occupied by microtubules. The results demonstrate that microtubules in diverse cells disassemble individually and asynchronously. In addition, these quantitative measurements reveal that epithelial and fibroblast cells display strikingly different kinetics of polymer loss. In fibroblasts, polymer loss is rapid, with a half-time of 4 min at 37 degrees C. In epithelial cells, loss of 60% of the microtubules occurs with a half-time of 18 min; the remaining 40% of the microtubules disassemble much more slowly (average half-time of 72 min). To demonstrate that these differences were not due to species differences among various cells assayed in these experiments, epithelial and fibroblast cells derived from primary cultures of newt lung have been examined. Again, fibroblast and epithelial cell microtubule dynamics could be readily distinguished. To determine if modifications to epithelial cell microtubules contribute to their stability, microtubules were completely disassembled and allowed to regrow. The rate of polymer loss for recently regrown microtubules was more rapid than microtubules in control cells, indicating that stability increases with time after assembly. PMID- 2190996 TI - Timing of nuclear and kinetoplast DNA replication and early morphological events in the cell cycle of Trypanosoma brucei. AB - We have used immunofluorescent detection of 5-bromo-2-deoxyuridine-substituted DNA in order to determine the timing of initiation and the duration of nuclear and kinetoplast S-phases within the procyclic stage of the Trypanosoma brucei cell cycle. Both nuclear and kinetoplast S-phases were shown to be periodic, occupying 0.18 and 0.12 of the unit cell cycle, respectively. In addition, initiation of both of these S-phases were in approximate synchrony, differing by only 0.03 of the unit cell cycle. We have also used a monoclonal antibody that recognises the basal bodies of T. brucei in order to visualise cells possessing a new pro-basal body and hence determine the time of pro-basal body formation within the cell cycle. Pro-basal body formation occurred within a few minutes of the initiation of nuclear S-phase, at 0.41 of the unit cell cycle. This provides detection of the earliest known cell cycle event in T. brucei at the level of the light microscope. Cell cycle events including initiation of nuclear and kinetoplast DNA replication and pro-basal body formation may be strictly coordinated in T. brucei in order to maintain the precise single-mitochondrion (kinetoplast), singleflagellum status of the interphase cell. PMID- 2190997 TI - How is microtubule-based organelle translocation regulated? PMID- 2190998 TI - Phosphorylation-related accumulation of the 125K nuclear matrix protein mitotin in human mitotic cells. AB - The preparation of mammalian cells for entry into mitosis is related to a cascade of G2 phase phosphorylations of several nuclear proteins driven by mitosis specific protein kinases. Using a monoclonal antibody we have identified previously in mammalian cells a 125K/pI6.5 protein, associated with the nuclear matrix, and markedly increased in mitotic cells, which was named 'mitotin'. Here, we show by short-term [35S]methionine labeling of cell cycle synchronized cells that this protein is synthesized at comparable rates throughout interphase. However, upon cycloheximide block of protein synthesis mitotin labeled during S phase is rapidly degraded, while the degradation of mitotin labeled during late G2 phase is abolished, resulting in its net and marked increase. The accumulation of mitotin in premitotic and mitotic cells is related to its phosphorylation and the metabolic stability of its two phosphorylated forms. The metabolic stabilization and accumulation of a nuclear matrix protein upon phosphorylation suggests the operation of a novel mechanism among the complex events preparing the cell for mitosis. PMID- 2190999 TI - Smoking out the oestrogens. PMID- 2191000 TI - Plasma androgens and oestradiol during oral glucose tolerance test in patients with polycystic ovaries. AB - Hyperinsulinaemia is common patients with polycystic ovaries (PCO), and a relationship between hyperinsulinaemia and hyperandrogenaemia has been suggested. We studied the effect of increased circulating insulin in response to an oral glucose tolerance test (OGTT) on plasma levels of androgens and oestradiol in PCO patients and in healthy control subjects. A 75 g, 3 h oral glucose tolerance test (OGTT) was performed in eight non-obese and seven obese PCO patients, and in 10 non-obese control subjects. An additional group of five women were fasting during the study period. The increase in insulin concentration was higher in obese and non-obese PCO patients than in non-obese control subjects, and the peak values were observed at 30 or 60 min. In the fasting control subjects, the mean concentration of androstenedione decreased slightly due to a diurnal variation. During the OGTT, mean concentrations of androstenedione decreased in all groups at 30 min, after which a slight increase was observed in PCO patients and a plateau in control subjects. Similarly, mean testosterone increased after an initial decrease in obese PCO patients whereas no change was found in non-obese PCO patients. No statistically significant differences were found in the responses of androstenedione or testosterone levels to OGTT in obese or non-obese PCO patients compared to normals. No significant responses of plasma oestradiol levels to OGTT were found. These findings failed to demonstrate any significantly abnormal acute androgen responses to OGTT-stimulated hyperinsulinaemia in PCO patients, but did not exclude possible long-term effects of hyperinsulinaemia. PMID- 2191001 TI - Rapid microbial detection and enumeration using gel microdroplets and colorimetric or fluorescence indicator systems. AB - A new micromethod employing gel microdroplets (GMDs) and optical measurements can be used for rapid detection and enumeration of viable microorganisms (J. C. Weaver, G. B. Williams, A. M. Klibanov, and A. L. Demain, Bio/Technology 6:1084 1089, 1988) and has several potential applications in clinical microbiology. This method involves entrapping microorganisms in GMDs (10 to 100 microns in diameter) which are surrounded by a hydrophobic (low dielectric) fluid, subsequently distinguishing occupied and unoccupied GMDs with colorimetric or fluorescence indicators, counting both occupied and unoccupied GMDs, and applying Poisson statistical analysis. Acid-producing microorganisms were used to compare colorimetric and fluorescence pH indicator systems. Fluorescence systems were generally superior, particularly for detection before microbial growth occurred. Although colorimetric detection was reasonably fast for fast-growing microorganisms, significantly longer times were needed for slow-growing microorganisms. We investigated the dependence of the detection time on microbial division time, GMD size, and buffering capacity of the medium within GMDs. It was found possible to use a single preparation of GMDs, containing a range of GMD sizes, to simultaneously provide a viable enumeration of growing and nongrowing (e.g., stressed) cells. This was possible because small GMDs responded rapidly to both growing and nongrowing cells, while large GMDs, although slower, responded much more rapidly to growing cells than to nongrowing cells. Separate analysis of small and large GMDs in the same preparation yielded two enumerations, one of nongrowing cells and the other of growing cells. GMDs can also be used with conventional light microscopy to detect and enumerate fast-growing acid-producing bacteria much more quickly than conventional plating methods. PMID- 2191002 TI - Identification of Campylobacter cinaedi isolated from blood and feces of children and adult females. AB - Five Campylobacter-like organisms isolated from blood and feces were identified by numerical analysis of gel electrophoretic protein profiles and immunotyping as Campylobacter cinaedi. Two of these strains were isolated from adult females; the remaining three strains were isolated from children, two of whom were girls. C. cinaedi has hitherto been isolated only from rectal swabs and blood of homosexual and bisexual males with gastrointestinal symptoms. The results presented extend our knowledge of the features and the habitat of C. cinaedi. PMID- 2191003 TI - Evaluation of five methods for respiratory syncytial virus detection. AB - A total of 117 nasal aspirates were cultured for respiratory syncytial virus (RSV) and tested for RSV antigen by a direct fluorescent-antibody (DFA) test (Bartels Immunodiagnostic Supplies, Inc., Bellevue, Wash.), the Directigen enzyme immunoassay (EIA; Becton Dickinson Microbiology Systems, Cockeysville, Md.), the TestPack EIA (Abbott Laboratories, North Chicago, Ill.), and RSV EIA (Abbott). Agreement of two of five methods or a positive RSV culture were required to validate a result. A total of 57 of 117 (48.7%) specimens were culture positive in HEp-2 cells, A549 cells, or both. A total of 5 of 117 (4.3%) additional specimens met the criteria of a positive specimen; i.e., 62 of 117 (53.0%) specimens were positive. Results obtained from 77 of 117 (65.8%) specimens were concordant for all five methods. The sensitivities, specificities, and positive and negative predictive values for the culture and DFA methods were 91.9, 100, 100, and 91.7% and 91.9, 96.4, 96.6, and 91.4%, respectively. The sensitivities, specificities, and positive and negative predictive values for the three EIA procedures, Directigen, TestPack, and RSV EIA, were 75.8, 80.0, 81.0, and 74.6%; 93.6, 100, 100, and 93.2%; and 71.0, 100, 100, and 75.3%, respectively. New self contained EIA configurations and the DFA method offer attractive alternatives to the culture method. Technical simplicity, rapid turnaround time, performance, and cost must all be considered when selecting a system for RSV detection. PMID- 2191004 TI - Septicemia caused by cysteine-dependent Escherichia coli. AB - A case of septicemia and urinary tract infection caused by cysteine-dependent Escherichia coli in a 70-year-old woman with bilateral staghorn calculi is described. This is the second report of a cysteine-dependent E. coli bacteremia. The bacterium was falsely susceptible to ampicillin and co-trimoxazole when tested on a medium without cysteine supplement. PMID- 2191005 TI - Isolation, identification, and characterization in Israel of Brucella melitensis biovar 1 atypical strains susceptible to dyes and penicillin, indicating the evolution of a new variant. AB - During characterization by conventional biotyping tests of numerous Brucella melitensis isolates obtained in Israel in the last 2 years, we identified several strains of the biovar 1 serotype that are atypically susceptible to dyes and penicillin. Their coisolation from two brothers in a family that rears sheep and from the milk of one of their sheep and the prevalence of such strains in two distinct geographical zones in Israel provide epidemiological support for the notion that a new variant has been identified. PMID- 2191006 TI - Detection of Candida antigenuria in disseminated candidiasis by immunoblotting. AB - Immunoblotting (Western blotting) was used to detect Candida albicans antigens in urine of 10 patients with disseminated candidiasis who had two or more positive blood cultures. Twelve urine samples were examined; and antigenuria was found in five of six patients with C. albicans infections, in one patient with a mixed Candida infection (including C. albicans), and in one of two patients with C. tropicalis infection. All except one specimen was collected from 2 to 12 days after initiation of amphotericin B therapy. Positive samples showed different numbers of bands in Western blots with an antigen that had an apparent molecular weight of 47,000 in common. This antigen was not found in the urine of patients who had more than 5 days of therapy for candidiasis and who were responding to therapy. The results suggest that Western blotting for C. albicans antigens in urine may be a useful method for the diagnosis of disseminated candidiasis and for evaluating antifungal treatment. PMID- 2191007 TI - Major subtypes of invasive Haemophilus influenzae from 1983 to 1985 in Atlanta, Ga. AB - We compared outer membrane protein (OMP) patterns of Haemophilus influenzae isolated in metropolitan Atlanta, Ga., from July 1983 to June 1985. Of 74 randomly selected H. influenzae serotype b, biotype I, isolates (24% of the total number of H. influenzae, and 32% of the total number of H. influenzae serotype b, biotype I, isolates), 66 (89.2%) had the same OMP pattern. Of the remaining eight, five (6.7%) had an identical OMP pattern. The other three isolates had separate and distinct patterns. A greater diversity of OMP patterns was found with H. influenzae serotype b, biotype II, and nonserotypeable H. influenzae. Of the 18 H. influenzae serotype b, biotype II, isolates (5.8% of the total number of H. influenzae isolates), 1 had an OMP pattern similar to that of the predominate biotype I OMP type, 6 (33% of the biotype II) had the same pattern, and 11 had heterogeneous patterns. Of the 19 recoverable, nonserotypeable biotype II isolates (6.8% of the total number of H. influenzae), 18 had different OMP patterns, and no pattern was similar to those observed with serotype b. These findings indicate that most H. influenzae strains isolated during this 2-year period were indistinguishable by serotype, biotype, or OMP patterns. PMID- 2191008 TI - Rabies diagnostic reagents prepared from a rabies N gene recombinant expressed in baculovirus. AB - A gene encoding the nucleoprotein (N) of rabies virus was inserted into the genome of the baculovirus Autographa californica nuclear polyhedrosis virus. Recombinant gene expression was controlled by the strong polyhedrin gene promoter. Insect cells (Spodoptera frugiperda) infected by a baculovirus recombinant containing the rabies virus N gene produced abundant amounts of a novel 55-kilodalton protein of a size comparable to that of the rabies virus N protein, as demonstrated by polyacrylamide gel electrophoresis. This new gene product possessed the antigenic and immunogenic properties of native viral N protein, as shown by the ability of the new protein to react in immunoprecipitation and immunofluorescence assays with antirabies antibodies, to serve as a substitute for infectious rabies virus in adsorbing suspensions for diagnostic tests, and to induce high-titered antiserum. The baculovirus expression system provides a safe, convenient, and inexpensive source of rabies virus N protein for the production of both antiserum and adsorbing suspensions for use in rabies diagnoses. PMID- 2191009 TI - Vibrio cholerae serogroup O1 in northeast Thailand. AB - Strains of Vibrio cholerae serogroup O1 biotype El Tor that are susceptible to Mukerjee cholera bacteriophage group IV (S. Mukerjee, Bull. W.H.O. 28:333-336, 1963) were found. Cholera vibrios isolated from epidemics in northeast Thailand were characterized, and 57 of 60 strains isolated in 1986 were susceptible to cholera phage IV. However, all 113 strains isolated in 1988 were not susceptible to the phage. All isolates in both epidemics revealed behaviors typical of El Tor vibrios, except phage IV susceptibility in the 57 strains. Although the plaques of phage IV were generally translucent, plaques on some isolates looked transparent, just like those on classical vibrios. The organisms grown in the plaques were lysogenized. If this kind of strain is frequently isolated, the biotype of V. cholerae O1 should be reconsidered. PMID- 2191010 TI - Electrophoretic karyotyping of typical and atypical Candida albicans. AB - Electrophoretic karyotypes of atypical isolates of Candida albicans, e.g., strains that were germ tube negative, failed to express proteinase activity, demonstrated low virulence for mice, formed hyperchlamydoconidia, produced hyperhyphae, or were sucrose negative (including the type strain of Candida stellatoidea), were compared with those of typical C. albicans. Karyotypes of whole-cell DNA of classical C. albicans examined with transverse alternating field electrophoresis under specific conditions were composed of seven DNA bands with a specific migration pattern. Certain atypical strains and representatives of the three serotypes of C. stellatoidea produced discrete karyotypes with 5 to 10 bands. All isolates demonstrated a significant degree of DNA relatedness, suggesting their conspecificity. Densitometric tracings of DNA bands provided an objective and standardized method for comparing bands within the gels. PMID- 2191011 TI - Comparison of two assay methods for patterns of adherence to HEp-2 cells of Escherichia coli from patients with diarrhea. AB - To determine whether methodological differences in the HEp-2 adherence assay could explain conflicting results of field studies, 244 strains of Escherichia coli from Mexican children with diarrhea were tested for patterns of adherence by the method used at the Center for Vaccine Development, University of Maryland (CVD), and at the Center for Infectious Diseases, University of Texas Medical School and School of Public Health (UTH). The CVD assay differentiated three phenotypes of adherent E. coli, including localized, diffuse, or aggregative adherence (LA, DA, or AA, respectively). There was agreement on pattern of adherence in 241 of the 244 strains (98.8%) tested by the CVD method in both Baltimore and Houston, and AA+ was the most common phenotype (28.5% of isolates). Among these isolates, the UTH assay detected only two adherent phenotypes (LA and DA), since it did not distinguish the AA pattern. The LA+ strains detected by each assay were compared for positivity with the enteropathogenic E. coli adherence factor (EAF) gene probe. Of the 16 strains LA+ by the CVD method, 100% were EAF+; in contrast, only 11 of 22 strains LA+ by the UTH method were EAF+ (P = 0.00074). These results help explain why in pediatric field studies in Mexico where isolates were tested by the UTH method (J. J. Mathewson, R. A. Oberhelman, H. L. Dupont, F. J. de la Cabada, and E. V. Garibay, J. Clin. Microbiol. 25:1917 1919, 1987) LA+ strains often did not belong to enteropathogenic E. coli O serogroups and why the AA pattern was not observed; the opposite was found in studies of pediatric diarrhea in Chile in which the CVD assay was used (M. M. Levine, V. Prado, R. M. Robins-Browne, H. Lior, J. B. Kaper, S. Moseley, K. Gicquelais, J. P. Nataro, P. Vial, and B. Tall, J. Infect. Dis. 158:224-228, 1988). Since it appears that both assays identify E. coli strains associated with diarrheal illness, the genetic relationships among these strains should be examined in future studies. PMID- 2191013 TI - Use of HL cells for improved isolation and passage of Chlamydia pneumoniae. AB - We compared growth of the recently discovered respiratory pathogen Chlamydia pneumoniae in McCoy, HeLa 229, BHK-21, and HL cells. When cells were not pretreated with DEAE-dextran, HL cells had significantly higher mean numbers of inclusion-forming units (IFUs) on initial inoculation than the other cell lines. When cells were pretreated with DEAE-dextran, HeLa 229 and HL cells had equivalent mean numbers of IFUs on initial inoculation. HL cells had strikingly higher mean numbers of IFUs in passage than HeLa 229, BHK-21, or McCoy cells. In addition, HL cells did not require pretreatment with DEAE-dextran and could be used from 2 to 4 days after seeding. We conclude that HL cells are an excellent cell culture system for laboratory propagation of C. pneumoniae and may be a more sensitive cell line for initial isolation. PMID- 2191012 TI - Protein G-based enzyme-linked immunosorbent assay for anti-MPB70 antibodies in bovine tuberculosis. AB - MPB70 is a highly species specific protein which is secreted from Mycobacterium bovis during culture. To investigate whether antibodies against MPB70 can be used as an indicator of infection with M. bovis, an enzyme-linked immunosorbent assay was developed, based on the use of biotinylated protein G, to provide a common indicator for antibody formation in different species. During experimental infection with M. bovis in cattle, a characteristic pattern of anti-MPB70 antibody production was observed with an initial flat plateau followed by a marked rise 18 to 20 weeks after infection. Skin testing with bovine tuberculin purified protein derivative (PPD), which was shown to contain antibody-reactive MPB70, was a potent stimulator of antibody production in infected animals. In experimentally infected cattle, we observed an inverse relationship between antibody activity and delayed-type hypersensitivity skin test reactions. In natural M. bovis infections, skin testing with PPD was also a potent stimulator of anti-MPB70 formation. Comparison between the enzyme-linked immunosorbent assay for antibodies to MPB70 and that for antibodies to the widely cross-reacting M. bovis BCG antigen 85B in animals with M. bovis, Mycobacterium avium, Mycobacterium paratuberculosis, and Corynebacterium pseudotuberculosis infections showed that formation of antibody to MPB70 was highly specific for infection with M. bovis. The use of an MPB70-containing PPD preparation for skin testing followed by this anti-MPB70 assay is a highly specific indicator of M. bovis infection. Adjustment of the test conditions is expected to provide an increased sensitivity of the procedure for the diagnosis of natural M. bovis infections. PMID- 2191014 TI - Swab-wash method for quantitation of cutaneous microflora. AB - We describe a comparison of the scrub-wash method of Williamson and Kligman and a swab-wash method for the enumeration of cutaneous microflora. The swab-wash method provides a less traumatic alternative to the scrub-wash method and can be used to sample the cutaneous microflora of premature neonates. PMID- 2191016 TI - ADP-ribosylation of actin. PMID- 2191015 TI - Immunodetection of human T-cell lymphotropic virus type I core protein in biological samples by using a monoclonal antibody immunoassay. AB - A monoclonal antibody-based enzyme immunoassay (EIA) has been developed for detection of human T-cell lymphotropic virus type I (HTLV-I) core protein. The monoclonal antibody (clone 6.11) specifically recognizes the p19 gag gene-encoded protein of the virus. The EIA was over 100 times more sensitive than reverse transcriptase measurement and was capable of responding to less than 500 pg of whole-virus lysate. The assay exhibited type specificity in that HTLV-II antigens failed to produce a positive signal. In addition, a panel of other viruses demonstrated no antigenic cross-reactivity. These included herpesviruses, measles virus, human immunodeficiency viruses, and others. Viral p19 was followed during the course of density gradient ultracentrifugation in the presence of detergent, where it was noted to associate with viral membrane proteins. In comparison, reverse transcriptase activity localized in fractions of higher density containing envelope-free cores. Of clinical interest, the EIA was used to detect HTLV-I antigen in the viral cultures of patients with HTLV-I-associated myelopathies and from symptom-free individuals with proviral integration. PMID- 2191017 TI - Noninvasive monitoring of renal blood flow characteristics during acute renal failure in man. AB - Duplex Doppler ultrasound (DDU) was used to study the blood flow characteristics of the renal interlobar artery in 20 subjects with acute renal failure (ARF), 14 subjects with transient impairment of renal function and 23 control subjects with normal function. Renovascular resistance was assessed by pulsatility index (PI) and change in flow velocity by change in mean frequency shift (delta f). The 99% confidence intervals for PI in the three groups were 3.32-5.46, 1.58-2.34 and 0.99-1.33 respectively. Values for delta f were 0.2-0.38, 0.5-0.62 and 0.7-1.02 kHz respectively. Ten ARF patients recovered function, 99% confidence intervals for PI just prior to recovery were 0.9-1.48 and for delta f 0.52-1.02 kHz. There was increased renovascular resistance and reduced intrarenal blood flow velocity at the onset of ARF. These changes persisted during ARF; recovery of function occurred after they returned to normal. Similar, but less marked, changes were found in patients with a transient impairment of function. PMID- 2191018 TI - Plasma catecholamine concentration during sedation in ventilated patients requiring intensive therapy. AB - The effects of isoflurane and midazolam sedation on the catecholamine responses of ventilated patients were studied over a 24-h period. Sixty ventilated patients admitted to our intensive therapy unit were allocated randomly to receive either isoflurane or midazolam sedation. Arterial blood samples for plasma catecholamine concentrations were taken at baseline, 6 h after starting sedation and at the end of the study period. Patients sedated with isoflurane showed a progressive reduction in both adrenaline and noradrenaline concentrations during the period of sedation which reached statistical significance for adrenaline at 6 h (p less than 0.02) and at the end of the study (p less than 0.001). Patients sedated with midazolam showed no significant changes of adrenaline or noradrenaline concentrations. Overall, a more satisfactory degree of sedation was achieved with isoflurane. PMID- 2191019 TI - P 0.1/PIMax: an index for assessing respiratory capacity in acute respiratory failure. AB - We studied airway occlusion pressure (P 0.1) and maximal inspiratory pressure (PIMax) in 10 healthy volunteers (Group A), 10 early postsurgical cardiac patients on spontaneous breathing (Group B), 10 patients mechanically ventilated for ARF (Group C), 10 patients weaning from mechanical ventilation after ARF (Group D) and 10 patients extubated after post-ARF (Group E). We calculated the index P 0.1/PIMax in an attempt to link the ventilatory demands and muscle ventilatory reserve. We found that the sensitivity and specificity in diagnosing the need for either full (C), partial (D) or no ventilatory support (A, B, E) by means of the P 0.1 were C = (50%, 95%), D = (70%, 72%) and A + B + E = (83%, 90%) respectively. When the index P 0.1/PIMax was used they were C = (90%, 100%), D = (80%, 87%) and A + B + E = (86%, 90%). We conclude that the index P 0.1/PIMax increases the reliability of P 0.1 alone to correctly classify the patients that will need either full, partial or no ventilatory support in ARF. PMID- 2191020 TI - Nonsurgical control of upper gastrointestinal hemorrhage in old age patients: intragastric norepinephrine and endoscopic alcoholization of lesions. AB - Of 28 consecutive patients over 64 years old, in whom endoscopy revealed gastro duodenal ulcers with signs of recent hemorrhage (active bleeding, non-bleeding vessel or adherent clot), 14 were randomly assigned to receive endoscopic alcoholization of the lesions preceded by intragastric instillation of norepinephrine, while as controls 14 received antacids. After the applied treatment the bleeding stopped in all cases (100%) in the study group and one patient died (7.1%) after hemostasis was achieved. In the control group bleeding stopped in 12 patients (85.7%). Two patients continued to bleed and needed emergency surgery. Another patient had a major rebleed successfully treated by alcoholization. There were 4 deaths (28%): 2 patients died postoperatively and the other 2 from acute porphyria and bronchopneumonia respectively. The transfusion requirements after the entry into trial were significantly lower in the study group compared to controls (mean no. of blood units 0.79 vs. 1.71). No complications were seen with the treatment applied. These results suggest that endoscopic alcoholization of the lesions preceded by intragastric instillation of norepinephrine is an effective and safe emergency therapy for bleeding from peptic ulcers in old age patients. PMID- 2191021 TI - Measurement of effective elastance of the total respiratory system in ventilated patients by a computed method. Comparison with the static method. AB - We have studied 28 patients mechanically ventilated for acute respiratory failure at different levels of externally applied positive end-expiratory pressure (PEEPe). We describe and compare a computed method of measuring "effective" elastance of the total respiratory system (Ers,eff) with the static values of elastance of the total respiratory system (Ers,st), obtained with the end inflation occlusion technique. Ers,eff was computed by an original device (Heres, R.P.A., Belgium), also the effective resistance of the total respiratory system was calculated. At zero end-expiratory pressure set by the ventilator (ZEEP). Ers,eff averaged 29.5 +/- 13.5 cm H2O x L-1 while Ers,st non-corrected for intrinsic PEEP (PEEPi) averaged 36.4 +/- 15.1 cm H2O x L-1 and Ers,st corrected for PEEPi averaged 28.2 +/- 13.4 cm H2O x L-1. The small difference between Ers,eff and Ers,st corrected for PEEPi was statistically significant and these two values were highly correlated (r = 0.98). This significant difference disappeared rapidly with PEEPe and probably reflects a frequency-dependance due to pendelluft. We also observed that PEEPi was present in 21 of 27 patients at ZEEP. Our results also indicate that low levels of PEEP may improve Ers in hyperinflated COPD patients, without inducing further hyperinflation. In conclusion, values of Ers,eff are very similar to static values corrected for PEEPi and permit an accurate and rapid approach to the management of ventilated patients. PMID- 2191022 TI - Cerebrospinal fluid lactate in 78 cases of adult meningitis. AB - In a retrospective study of 78 cases of adult meningitis, the CSF lactate was measured on the first spinal tap (ST); 25 had a bacterial meningitis, 28 a viral meningitis; 22 other cases had been on antibiotics prior to admission; 3 cases had meningitis of rare aetiology. The median CSF lactate level among the 25 bacterial cases amounted to 13.6 mmol/l (range: 3.5-24.5) whereas it remained low in the 28 viral cases: 2.7 mmol/l (range: 1.4-4.2). These differences are highly significant. The comparison of the CSF lactate level with the other tests routinely performed showed that the CSF lactate level had the highest sensitivity, specificity and predictive values. The CSF lactate level on the first ST had no prognostic value, but a rapid decrease of the CSF lactate during the treatment is indicative of good prognosis. Among the pretreated cases, a high lactate level could be an indication that bacteria were the causal agents. In conclusion, the measurement of the CSF lactate, quickly performed and inexpensive, is worth performing when a meningitis is suspected, as it appears to be the best way of distinguishing bacterial from non-bacterial meningitis. PMID- 2191023 TI - Dental education: embarking on a new era. PMID- 2191024 TI - New programs for advanced training in dental geriatrics. AB - The unprecedented increase in the number and percentage of Americans who are older than the age of 65 is presenting the health care system with unique diagnostic, therapeutic, fiscal, and ethical challenges. Chronic disease, complex pharmacotherapeutic regimens, and psychosocial and physical dysfunction are prevalent in this age group. The dental profession is faced not only with an increase in the number and complexity of older patients, but with the fact that growing numbers of older patients are retaining a greater proportion of their natural dentitions for longer periods. To help meet the need for increased professional skill to deal with these issues, the Health Resources and Services Administration of the Department of Health and Human Services is supporting 23 medical school based geriatrics training programs, designed expressly for physicians and dentists. The programs offer a mixture of experiences in: clinical care of the elderly in a variety of settings; design and conduct of research relevant to geriatric and gerontologic issues; enhancement of pedagogical skills; and program administration. Physicians and dentists share many of the training experiences, providing both groups with unique insights into the presentation and management of their patients' problems, and an enriched awareness of each other's contributions to the care of the elderly. PMID- 2191025 TI - Diagnosis and treatment of orofacial herpes zoster: report of cases. AB - Herpes zoster is considered a disease of elderly or immunocompromised patients. These cases are unusual since clinical signs of the disease occurred in two healthy, young adults. Various diagnostic and treatment considerations for herpes zoster infections are presented. PMID- 2191026 TI - Dentistry on stamps. PMID- 2191027 TI - Blindness following minor head trauma in children: a report of two cases with a review of the literature. AB - The spectrum of closed head injury ranging from asymptomatic to lethal is well described in the literature. In a small number of cases, dramatic neurologic symptoms normally associated with cerebrovascular accident or vascular headache may arise following apparently insignificant head trauma. We report two cases of young males who developed transient blindness accompanied by significant neurologic abnormality following trivial head injuries. These phenomena are previously well documented, and it is believed that in certain individuals, minor head trauma can induce a type of migraine equivalent known as "footballer's migraine" or "posttraumatic cortical blindness." Current knowledge of these two conditions is reviewed. PMID- 2191028 TI - Arterial injury from a high pressure water jet: case report. AB - We report the case of a patient who sustained a high-pressure water jet injury to the thigh while cleaning industrial piping. The patient presented with a puncture wound to the anterior thigh and a pulseless foot. Emergency arteriography was performed that revealed complete disruption of the superficial femoral artery. The patient underwent surgical exploration and debridement, and a successful repair of the disrupted artery was performed with a prosthetic arterial graft. A discussion of high-pressure water jet injuries and their management is presented. PMID- 2191029 TI - Cardiac arrest secondary to indomethacin-induced renal failure: a case report. AB - Acute renal failure secondary to nonsteroidal anti-inflammatory agents is an uncommon occurrence, but may have serious or even lethal consequences. We present one such reaction resulting in cardiac arrest in a 59-year-old diabetic treated with indomethacin. Since presenting symptoms may be vague and unimpressive, one must consider this potential complication to make an early diagnosis and intervene appropriately. In addition when prescribing anti-inflammatory drugs such as indomethacin, one should be cautious in patients who are predisposed to the development of acute renal failure. Risk factors that should be considered are preexistent hepatorenal dysfunction, extracellular fluid volume contraction, and concomitant use of nephrotoxic drugs. PMID- 2191030 TI - Lithium toxicity and myxedema coma in an elderly woman. AB - The development of hypothyroidism as a side effect of lithium therapy is a well recognized phenomenon. However, the presentation of myxedema coma after lithium intoxication has not been previously documented. In this case lithium toxicity may have exacerbated preexisting hypothyroidism to the point of respiratory arrest. Based on this case, we recommend periodic monitoring of thyroid function in an effort to detect preexisting hypothyroidism or lithium-induced hypothyroidism. PMID- 2191031 TI - Penetrating neck trauma: mandatory versus selective exploration. PMID- 2191032 TI - Deep venous thrombosis of the upper extremity: diagnosis and treatment. AB - Deep vein thrombosis of the upper extremity was long thought to be a benign disease, rarely complicated by pulmonary embolism and associated with minimal long-term morbidity. More recent observations have demonstrated however, that a significant number of patients will continue to have disabling symptoms after treatment with conservative measures and standard anticoagulation therapy, and that pulmonary embolism can occur in the course of the disease. Because of its significant morbidity and increasing incidence, an aggressive emergency department approach to diagnosis and early consideration of fibrinolytic therapy are recommended. PMID- 2191033 TI - Immunity in sportsmen. AB - Generalization and analysis of literature data on the state of nonspecific defense and immunity in sportsmen has demonstrated that moderate physical and psycho-emotional loads promote stimulation and normalization of nonspecific defense and immunity; intensive subextreme and extreme loads of modern sport, exceeding functional possibilities of the organism, cause inhibition of a number of indices of nonspecific defense, T- and B- systems of immunity. The necessity of using immunological methods in hygienic norm-setting of training loads has been pointed out. PMID- 2191034 TI - Rheumatic fever and streptococcal infections in an isolated population group in eastern Siberia. AB - During a two-week expedition, the prevalence of rheumatic heart disease (RHD) and the prevalence of group A streptococcal infections was investigated in a group of Yakut families of about 600 persons. In the 478 examined persons no clear-cut RHD was identified, but possible participation of rheumatic etiology in heart changes was not excluded in one adult. Group A streptococci were grown from pharyngeal swabs from 13.3% of the 202 persons examined, in the absence of any overt streptococcal disease in the settlement at the time of screening. Streptococci of at least six M-types were present among the population. Titres of antistreptolysin 0 greater than or equal to 250 u. and of antideoxyribonuclease-B greater than or equal to 1200 u. were found in 21% and 18%, respectively, of the 205 examined individuals. The bacteriological and serological data combined suggested a rather high streptococcal transmission rate in the settlement in the recent past, the pattern of which was reminiscent of the pattern of streptococcus spread in heavily interconnected population groups of the moderate climate. Possible reasons for the absence of definite RHD are discussed. PMID- 2191035 TI - To the problem of Campylobacter jejuni detectability in water. AB - In a series of model experiments two isolation procedures for the detection of water-borne Campylobacter jejuni were compared: a standard culture in thioglycolate broth enriched with 7% defibrinated sheep blood and supplement C and a modified membrane filtration method in which the filter (porosity 0.45 microns) plated on campylobacter agar surface was removed after the first 24 hours of incubation and the plate further incubated for 48 hours. The recovery rates by the thioglycolate broth method were markedly less pronounced than those obtained by the modification of membrane filtration technique, especially in the case of water rich in organics. The best isolation parameters were achieved with water samples of at least 10 ml in volume. PMID- 2191036 TI - Confirmation of Morganella distinction from Proteus and Providencia among Enterobacteriaceae on the basis of cellular and lipopolysaccharide fatty acid composition. PMID- 2191037 TI - Laboratory criteria in the diagnostics of intestinal infections of staphylococcal etiology in children. AB - Faecal samples were investigated from 948 children hospitalized with the diagnose of acute intestinal infection. The authors studied the isolation and properties of a broad spectrum of microorganisms from children's faeces: Salmonella, Shigella, E. coli, S. aureus, rotaviruses, Klebsiella, Morganella, Proteus. As a result, laboratory criteria were formulated of diagnosing in children intestinal infection of staphylococcal etiology. PMID- 2191038 TI - IL-1 activity is reduced in psoriatic skin. Decreased IL-1 alpha and increased nonfunctional IL-1 beta. AB - IL-1 may influence or be influenced by a number of abnormalities present in psoriasis; including keratinocyte proliferation, eicosanoid production, fibroblast activation, endothelial cell adhesiveness, T cell infiltration and activation, cyclic nucleotide metabolism, and transmembrane signal transduction mechanisms. We assessed IL-1 regulation in normal, uninvolved, and involved skin of psoriatic patients using immunofluorescence microscopy, a sensitive ELISA method to quantitate immunoreactive IL-1 beta and IL-1 alpha protein levels, the thymocyte proliferation costimulation assay, costimulation of the LBRM.33 IL-1 sensitive cell line, and Northern blotting of cellular RNA to quantitate IL-1 alpha and beta mRNA. IL-1 beta was easily detectable by immunofluorescence microscopy and found to be localized predominantly in epidermal keratinocytes, whereas IL-1 alpha was not detectable with this method. Immunoreactive IL-1 beta was found to be elevated in cytosolic extracts derived from involved psoriatic keratomes relative to keratomes of normal skin. The elevated IL-1 beta protein was accompanied by elevated levels of IL-1 beta mRNA in psoriatic skin relative to normal skin. In contrast, immunoreactive IL-1 alpha levels were markedly reduced in lesional psoriatic skin. In functional assays using both the thymocyte proliferation assay and the LBRM.33 cell line, IL-1 activity from psoriatic involved skin keratomes was markedly reduced relative to that of uninvolved psoriatic keratomes and normal skin. All activity of both normal and psoriatic skin was attributable to IL-1 alpha. The elevated IL-1 beta immunoreactive protein present in psoriatic skin was found to be functionally inactive in these assays. The inactivity of the IL-1 beta was not due to an artifact of the cytosolic method of preparation because IL-1 beta released by psoriatic skin into the media was also nonfunctional. This was in keeping with the demonstration that the IL-1 beta was nonfunctional despite existing as a processed molecule. Taken together, these data demonstrate uncoordinated regulation of IL-1 alpha and Il-1 beta in psoriasis. The profound and complex changes in this system suggest IL-1 dysregulation may be integrally involved in the inflammatory, biochemical, and proliferative processes involved in the pathophysiology of psoriasis. PMID- 2191039 TI - Gene-expression and release of macrophage-colony stimulating factor in quiescent and proliferating fibroblasts. Effects of serum, fibroblast growth-promoting factors, and IL-1. AB - Macrophage (M)-CSF induces the proliferation and differentiation of macrophage precursor cells, and is an important factor in the survival and activation of mature mononuclear phagocytes. Several effector cell populations such as mononuclear phagocytes, endothelial cells, and fibroblasts, have been reported to produce M-CSF at high levels. We investigated the gene-expression and release of M-CSF in fibroblasts. Quiescent, growth-arrested, fibroblasts showed little expression of M-CSF as demonstrated by Northern blot analysis, and little production of M-CSF as measured in the murine bone marrow bioassay. Initiation of proliferation of fibroblasts by fetal bovine serum was followed by an increase in M-CSF transcription and release of the protein. Similarly, single factors (platelet-derived growth factor) or combinations of factors (epidermal growth factor (EGF) + insulin, platelet-derived growth factor + EGF + insulin, or fibroblast growth factor + EGF + insulin) that induced proliferation of the fibroblasts, also induced increased expression of M-CSF. As soon as 1 h after the addition of fetal bovine serum, M-CSF expression was increased, and reached a plateau at 2 to 8 h after induction. IL-1 increased M-CSF expression both in quiescent and proliferating fibroblasts, and induced the expression and release of granulocyte-, and granulocyte/macrophage-CSF. These results show that expression of M-CSF in fibroblasts is not constitutively at a high level, but undergoes regulation depending on the cellular proliferative state and on further activation by acute response proteins such as IL-1. PMID- 2191041 TI - Single incubation multilayer immune technique. AB - A new method termed the 'single incubation multilayer immune technique (SIMIT)' is described which features two striking advantages over standard immunoassay techniques: shorter assay time and superior assay sensitivity. Using standardized, optimized amounts of ligand (e.g., antibodies) and anti-ligand (e.g., anti-antibody) it is possible to co-incubate these two reactants so that during a single incubation step multiple layers of immunoreactants are formed thereby resulting in enhanced assay sensitivity. Depending upon the application, SIMIT improves detection levels by about 10-20-fold. This report describes the use of SIMIT for two completely different assay systems: (a) indirect enzyme linked immunosorbent assays, and (b) unlabeled enzyme immunoassays. However, SIMIT should be applicable to a large variety of other assay systems. PMID- 2191040 TI - The major Leishmania donovani chagasi surface glycoprotein in tunicamycin resistant promastigotes. AB - Two populations of Leishmania donovani chagasi promastigotes resistant to the lethal effects of tunicamycin (TM), an inhibitor of N-linked glycosylation, were raised. These parasites exhibited altered patterns of glycosylation when compared to wild-type controls. In particular the major surface glycoprotein gp63 was present in membranes of one population of TM-resistant promastigotes (population 1) primarily in a deglycosylated form, which migrated at a lower Mr than wild type gp63. The deglycosylated protein was proteolytically inactive on substrate containing gels, in contrast to glycosylated gp63. Assays of promastigote attachment to human macrophages revealed that, despite a proposed role for gp63 protease activity in binding to macrophage receptors, population 1 TM-resistant promastigotes appeared to attach to the CR3 but not to the mannose-fucose receptor. Control promastigotes bound to both receptors. In contrast, a second population of TM-resistant promastigotes (population 2) did not produce gp63 that could be detected on immunoblots, either in a glycosylated or deglycosylated form. The latter TM-resistant promastigotes bound to neither CR3 nor the mannose fucose receptor, suggesting that expression of gp63 might be important for promastigotes to bind to CR3. LPG was present in immunoblots of both TM-resistant and control populations suggesting this molecule might not account for the differences in attachment. Surprisingly both TM-resistant promastigote populations contained gp63 mRNA by Northern analysis in apparently equal amounts. We conclude that N-glycosylation is probably necessary for the protease function of gp63, but that neither N-glycosylation nor protease activity of gp63 is necessary for L. donovani chagasi promastigotes to bind to CR3. Furthermore the expression of gp63 protein by TM-resistant promastigotes is dependent upon postranscriptional events. PMID- 2191042 TI - Technical aspects of typing for HLA-DP alleles using allele-specific DNA in vitro amplification and sequence-specific oligonucleotide probes. Detection of single base mismatches. AB - The polymerase chain reaction (PCR) is an effective method for in vitro DNA amplification which combined with probing with synthetic oligonucleotides can be used for, e.g., HLA-typing. We have studied the technical aspects of HLA-DP typing with the technique. DNA from mononuclear nucleated cells was extracted with either a simple salting out method or phenol/chloroform. Both DNAs could be readily used for PCR. The MgC2 concentration of the PCR buffer and the annealing temperature of the thermal cycle of the PCR were the two most important variables. The MgCl2 concentration and the temperature must be carefully titrated for each primer pair in the PCR. The influence of mismatches between the primer and the DNA template were studied and we found that, by using primers differing only from each other at the 3' end, cross-amplification of closely homologous alleles could be avoided. Thus, single base mismatches may be detected in the PCR and typing for HLA-DP gene variants, which differ for only one base, may be performed. PMID- 2191043 TI - Modification, optimization and simplification of the spot ELISA technique for the enumeration of cells secreting anti-hapten antibodies. AB - We describe here a modification of the spot ELISA assay for the detection and enumeration of antibody-secreting cells. The modification increases sensitivity, convenience and simplicity while optimizing parameters of time, temperature and reagents. Laboratory reagents and 96 well microtiter plates commonly used for the standard ELISA assay are adapted for use in the spot ELISA assay. Special emphasis is placed on the detection of anti-hapten IgM or IgG production by splenocytes in response to stimulation by a range of doses of antigen. In addition, two procedures are described whereby the spot ELISA assay is altered to yield a measurable optical density: (1) the blue precipitate obtained in the spot ELISA assay is dissolved and the optical density of the resultant blue color is measured, and (2) a standard ELISA substrate is substituted for the spot ELISA substrate to yield a colored solution rather than a precipitate. Both of these are shown to correlate with spot numbers and can therefore supplement or substitute for the enumeration of spots (produced by antibody-secreting cells), thus speeding and mechanizing the assay. PMID- 2191044 TI - Cross-reactive affinity purification of immunoglobulin recognizing common gram negative bacterial core antigens. AB - A procedure isolating immunoglobulins specific for common gram-negative bacterial core antigens is described. A polyclonal reagent was purified by ammonium sulfate precipitation, dialysis, and column affinity chromatography. The initial vaccinal antigen was an Ra mutant Escherichia coli O111:B4 (strain J5). The capture antigen was lipopolysaccharide derived from an Ra mutant, Salmonella typhimurium TV119 covalently-linked to an agarose matrix. Column eluants were characterized in terms of total protein concentration, IgG concentration, and EIA titer recognizing E. coli (J5). Low protein, low IgG, high EIA reading fractions were isolated, demonstrating the utility of the described technique to purify broad spectrum cross-reactive immunoglobulin reagents. PMID- 2191045 TI - Flow sorting of hybrid hybridomas using the DNA stain Hoechst 33342. AB - A two-step sorting procedure with the fluorescence-activated cell sorter (FACS) is described for the selection of hybrid hybridomas producing bispecific monoclonal antibodies. Parental hybridoma cells were first labelled before fusion with fluorescein isothiocyanate (FITC) and tetramethyl rhodamine isothiocyanate (TRITC); heterofluorescent cells were recovered after fusion. After a period of growth in culture, the cells were then stained with the DNA-specific dye bis benzimidazole Hoechst 33342 and sorted on the basis of their DNA content. The staining conditions (10 micrograms/ml of Hoechst 33342, 90 min incubation time at 37 degrees C) were found to be optimal for obtaining a well resolved DNA histogram with minimal effect on the growth properties of cells from different mouse hybridoma lines. Employing this method we have isolated hybrid hybridomas synthesizing bispecific monoclonal antibodies reacting with human low density lipoprotein and alkaline phosphatase from calf intestine. PMID- 2191046 TI - Founders lecture. Richard Roksabro Kudo, the man and his hobby. PMID- 2191047 TI - The class II major histocompatibility complex antigen deficiency syndrome: consequences of absent class II major histocompatibility antigens for lymphocyte differentiation and function. AB - The class II major histocompatibility complex antigen deficiency syndrome is a rare immunodeficiency disease associated with defective expression of the class II antigens encoded for by the major histocompatibility complex. Clinically, this syndrome is manifest as a combined immunodeficiency presenting early in life, and affected individuals are susceptible to a variety of severe and/or opportunistic infections. Chronic, severe diarrhea and malabsorption are also characteristically found, and death is common within the first few years of life. Although the precise molecular lesions responsible for the failure of membrane antigen expression in this syndrome have not yet been identified, the pathogenetic mechanisms involve regulatory defects in the transcription of structural genes encoding for class II antigens. The absence of class II MHC antigens results in profound abnormalities in lymphocyte function and differentiation. Of central importance is the defective MHC-restricted interactions between CD4+ "helper" T lymphocytes and the various types of antigen presenting cells found in the skin and elsewhere. The absence of class II MHC antigens also appears to alter the ability of affected B cells to be activated by a variety of membrane-mediated stimuli, and it profoundly disrupts both the intrathymic development and post-thymic differentiation of immunoregulatory T cells. This "experiment of nature" thus demonstrates the critical role of class II MHC antigens in the proper development and function of the immune system. PMID- 2191048 TI - Studies of C3d,g in normal human epidermal basement membrane. AB - Recent studies in our laboratory have demonstrated that polyclonal as well as monoclonal antibodies directed against C3d,g, a specific 41,000-Da fragment of the third component of complement, bind normal human epidermal basement membrane in a continuous pattern. No such reactivity is present within dermal microvascular basement membranes. By direct immunofluorescence microscopy, anti human C3d,g antibodies bind the base of the cleavage plane in 1 M NaCl split human skin. By immunoelectron microscopy, anti-human C3d,g reactivity is found along the base of the lamina densa and in the sublamina densa region. Control antibodies directed against human C3, C3c, C5, IgG, IgA, or IgM do not bind normal human epidermal basement membrane or identify in situ deposits of immune complexes in multiple samples of normal human skin that are all positive for C3d,g. Preabsorption of monoclonal or polyclonal anti-human C3d,g antibodies with purified human C3d completely blocks these reagents' epidermal basement membrane reactivity. Studies of skin samples from a patient with congenital C3 deficiency reveal that anti-human C3d,g antibodies do not bind this subject's epidermal basement membrane. Moreover, in vitro treatment of this patient's skin with normal serum, aged serum containing C3d,g, purified human C3, or zymosan-serum reaction mixtures does not restore epidermal basement membrane anti-human C3d,g binding. Studies of other primate tissues demonstrate that C3d,g is not restricted to basement membranes of stratified squamous epithelia as it is also present within renal tubule and glomerular basement membranes. While a recent study has demonstrated that C3d binds laminin in vitro, our investigations show a difference in both the regional and ultrastructural distribution of laminin and C3d,g in normal human skin. Furthermore, C3d,g is absent from laminin-rich basement membranes of papulonodular basal cell carcinomas. These findings suggest that C3d,g is not passively incorporated within selected epithelial basement membranes but rather is a previously unrecognized normal constituent. Basement membrane-associated C3d,g may play a role in adhesive interactions between leukocytes and matrix proteins. Moreover, a C3d,g binding site(s) in selected epithelial basement membranes may account for the accumulation of C3 containing immune complexes in such tissues. PMID- 2191049 TI - Fc receptors of human Langerhans cells. AB - Receptors for the Fc fragment of immunoglobulins (Fc R) exhibit specificities for a wide variety of immunoglobulin classes and subclasses. In humans, at least three distinct classes of receptors for the Fc fragments of IgG (Fc gamma RI, II, III) and two classes of receptors for the Fc fragments of IgE (Fc epsilon RI, II) have been characterized. These classes were largely defined on the basis of their affinities for different immunoglobulin subclasses and their reactivities with monoclonal anti-receptor antibodies. Among these FcR, in healthy individuals, epidermal Langerhans cells (LC) express only the Fc gamma RII/CDw32. This FcR--a member of the immunoglobulin superfamily--is only present on about 50% of freshly isolated CD1a positive cells, as determined by rosette assays. It has a Mr of 40 kDa, is trypsin resistant, binds polymeric human IgG and murine IgG1-coated erythrocytes, and reacts with anti-CDw32 monoclonal antibodies (MoAb). LC internalize Fc gamma RII by receptor-mediated endocytosis. After 48 h of culture, human LC loose their Fc gamma RII, as revealed by flow cytometry. While the function(s) of the Fc gamma RII on human LC remain(s) unknown, this receptor may be primarily involved, like the Fc gamma RII present on mouse macrophages, in the clearance of extra-cellular immune complexes. In patients with atopic dermatitis having an elevated IgE serum level, beside an increased expression of the Fc gamma RII by LC located on lesional skin, IgE-bearing epidermal and dermal LC are present, again essentially on lesional skin. Double immunolabeling on cryosections reveals that on lesional skin only about 50% of the epidermal CD1a positive cells bear IgE. This capacity of LC to bind IgE molecules appears to be due to the presence of a specific Fc epsilon R. While the class of this Fc epsilon R still remains unclear, it appears to have some particularities: i) an associated expression with the CD1a antigen, ii) an affinity for IgG, and iii) a trypsin resistance. In vitro, human recombinant interleukin (IL)-4 and/or interferon (IFN)-gamma are able to induce the synthesis and expression of Fc epsilon RII/CD23 on a percentage of normal human epidermal LC. This Fc epsilon RII seems to be functional since it binds IgE molecules, this binding being prevented by preincubation with anti-CD23 MoAb.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2191051 TI - The EGF/TGF alpha receptor in skin. AB - In responsive cells, all known effects of epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), and related proteins are mediated through binding to a specific membrane receptor. The EGF/TGF alpha receptor is a single-chain glycoprotein (1186 amino acids) containing three functional domains: 1) an extracellular, glycosylated portion that binds EGF; 2) a small transmembrane portion; and 3) a cytoplasmic portion that has the intrinsic tyrosine kinase activity and multiple sites that can be phosphorylated. When EGF binds to the receptor its intrinsic tyrosine kinase is activated, resulting in increased phosphorylation of intracellular tyrosine residues both on the receptor (autophosphorylation sites) and on exogenous proteins involved in regulating cellular functions. Site-specific mutagenesis has established that the tyrosine kinase activity of the receptor is essential for nearly all of the effects of EGF including its ability to elevate cellular calcium levels and to induce DNA synthesis. The binding of EGF and the kinase activity of the receptor are both regulated by the phosphorylation of the receptor on specific threonine/serine sites catalyzed by other protein kinases. Specific lipids such as sphingosine also can regulate kinase activity. Tyrosine-specific phosphoprotein phosphatases and perhaps proteases must be important in terminating the cellular response to EGF. In human skin, the response to EGF/TGF alpha is determined by the location and number of receptors and is modulated by processes affecting the binding affinity, internalization, and tyrosine-kinase activity of the receptor. Specific patterns of EGF binding and of immunoreactive receptors characterize normal growth and differentiation and these are altered during the abnormal growth and differentiation associated with diseases such as psoriasis, viral infections, neoplasms, and paraneoplastic syndromes. It is not clear if the altered patterns reflect the consequence of the disease or are the cause of the disease. As a cause, the EGF receptor may have undetected point mutations that result in internalization and degradation defects, aberrant phosphorylation, and dephosphorylation or abnormal glycosylation. PMID- 2191050 TI - The role of adhesion molecules, chemotactic factors, and cytokines in inflammatory and neoplastic skin disease--1990 update. AB - In 1986 it was discovered that cultured human keratinocytes, when treated with gamma interferon, attract and bind T lymphocytes and monocytes. More is now known about trafficking of inflammatory cells in the skin, with specific molecular details involving various cytokines, chemotactic factors, and adhesion molecules. One key element is the in vivo movement of T cells that express LFA-1 into the epidermis, and their subsequent binding to keratinocytes via the surface expression of intercellular adhesion molecule-1 (ICAM-1). This interaction represents a common immunologic pathway, which has been identified in a wide variety of different skin diseases. This review provides a synopsis of advances in this field, which have grown rapidly during the past few years, and adds recent results dealing with coordinate regulation at the gene-transcriptional level of keratinocyte chemotactic factor production and adhesion molecule expression. Moreover, epidermal keratinocytes appear to play a pre-eminent role in the skin, serving as transducing elements converting exogenously applied low molecular-weight chemical stimuli such as phorbol ester and urushiol (the active ingredient in poison ivy extracts) into the production of endogenously derived immunoregulatory proteins. These keratinocyte-derived molecules may then influence immunocytes and endothelial cells to further amplify the inflammatory response. The identification of keratinocyte-derived molecules such as IL-8 and ICAM-1, which influence the chemotaxis and adherence of T cells, adds substantial evidence supporting an active participatory role for keratinocytes in cutaneous immunohomeostasis. Finally, we highlight the importance of these immunoregulatory molecules in two malignant cutaneous disorders (cutaneous T-cell lymphoma and basal-cell carcinoma) and attempt to integrate these new findings into novel pathophysiologic models for two inflammatory dermatoses (rhus dermatitis and psoriasis). PMID- 2191052 TI - Interleukin-6: molecular pathophysiology. AB - The cytokine interleukin-6 (IL-6) has emerged as a major systemic alarm signal which appears to be produced by essentially every injured tissue. Recent evidence points to the skin, particularly the injured skin, as one of the major sites of IL-6 production. The hallmark of IL-6 gene regulation is its induction by inflammation-associated cytokines, bacterial products, virus infection, and activation of any of the three major signal transduction pathways (diacylglycerol , cAMP-, and Ca(++)-activated). Many of these inducers act largely through a 23 bp "multiple-response element" in the IL-6 promoter. Different cell types, including keratinocytes, secrete multiple post-translationally modified forms of IL-6. This cytokine, in turn, plays a key role in activating a variety of local and systemic host defense mechanisms that are aimed at limiting tissue injury. Thus, IL-6 elicits major changes in the biochemical, physiologic, and immunologic status of the host (e.g., the "acute phase" plasma protein response; activation of B, T, and NK-cell function). IL-6 enhances the proliferation of human keratinocytes and of many B-cell lines but inhibits that of certain carcinoma cell lines; nevertheless, IL-6 can enhance the motility of these carcinoma cells. Elevated levels of IL-6 are observed in human body fluids during acute and chronic infections, neoplasia, autoimmune diseases, and psoriasis and following third-degree burns. It is likely that IL-6 produced by cellular elements in the skin represents an important means of communication between the external environment and the millieu interieur. PMID- 2191053 TI - Cellular mechanisms of TGF-beta action. AB - Transforming growth factor beta (TGF-beta), initially identified in platelet extracts by virtue of its ability to confer anchorage-independent growth and a neoplastic phenotype on mesenchymal cells, has subsequently been identified as a potent inhibitor of proliferation in most cells of epithelial origin. Our laboratory has investigated the role of specific second messengers in mediating the transcriptional responses of fibroblasts following addition of TGF-beta 1. Our studies indicate that TGF-beta 1, alone and in conjunction with epidermal growth factor (EGF), is capable of stimulating increases in both phosphoinositide metabolism and calcium influx, leading to significant increases in intracellular levels of Ca++ and inositol trisphosphate (IP3). Our data indicated that Ca++ influx and inositol phosphate release are coupled in Rat-1 cells, and suggested that influx of Ca++ from the extracellular medium is required for the change in IP3 accumulation observed in response to both EGF and TGF-beta 1. Using nuclear run-on analysis of the transcription of rat transin, a secreted metalloproteinase homologous to human stromelysin, we have also demonstrated a significant inhibition of transin transcription within 10 min of TGF-beta 1 treatment. The ability of TGF-beta 1 to inhibit transin gene transcription was not related to the TGF-beta 1-induced influx of Ca++ or to an increase in intracellular inositol phosphates, since inhibiting production of these second messengers failed to inhibit repression of the transin gene. PMID- 2191054 TI - Organ-specific and non-organ-specific lymphocyte receptors for vascular endothelium. AB - The recirculation of lymphocytes from blood to lymph and back to blood is necessary for the proper functioning of the immune system as it facilitates interactions between antigen-reactive clones of lymphocytes and antigen presenting cells. The first step in the emigration of a blood-borne lymphocyte into either a secondary lymphoid organ or an inflammatory lesion is its adherence to vascular endothelial cells (EC) lining unique post-capillary venules known as high endothelial venules (HEV). Several groups have recently cloned and sequenced genes which may encode organ-specific lymphocyte receptors for the EC of such HEV. The extracellular portion of the putative murine lymphocyte homing receptor for peripheral lymph node HEV is composed of an N-terminal lectin-like domain, followed by an epidermal growth factor-like domain, and then two identical repeating domains which are homologous to a number of complement-binding proteins. A hydrophobic transmembrane domain and a cytoplasmic tail complete the structure. A very similar gene structure has been reported for a cytokine inducible EC surface protein which is involved in neutrophil-EC adhesion in vitro. In marked contrast, the gene for a putative human lymphocyte homing receptor appears to belong to a gene family which encodes cell-surface molecules with receptor activity for extracellular matrix (ECM) proteins. Similarly, the cell-surface molecule which appears to be the murine lymphocyte receptor for Peyer's patch HEV is homologous, if not identical, to the human VLA-4 molecule, another receptor with binding activity for an ECM protein. It has also been demonstrated that lymphocyte function-associated antigen 1 (LFA-1) acts in a non organ-specific manner to mediate lymphocyte-EC adhesion. Finally, other non-organ specific lymphocyte adhesion molecules for EC may include CD4 and CD8 (which bind to class II and class I MHC antigens, respectively), and CD2 (which binds to LFA 3). PMID- 2191055 TI - Fc receptors for IgE and interleukin-4 induced IgE and IgG4 secretion. AB - IgE binds to two types of Fc receptors, called Fc epsilon R1 (or high-affinity Fc epsilon R) and Fc epsilon R2 (or low-affinity Fc epsilon R). The Fc epsilon R1 is composed of four polypeptide chains, one alpha, one beta, and two gamma chains. The alpha chain contains the IgE binding site and is a member of the immunoglobulin supergene family. The Fc epsilon R2, also called CD23, consists of one polypeptide chain which shows homology to animal lectin receptors. Fc epsilon R1 are expressed on mast cells and basophils. Crosslinking of the Fc epsilon R1 induces immediate release of mediators of inflammation such as histamine and leukotrienes and delayed secretion of interleukins 4, 5, and 6. Fc epsilon R2 are expressed on resting mu delta + B cells, monocytes/macrophages (M phi), eosinophils, and platelets but rarely on T cells. Interleukin-4 upregulates Fc epsilon R2 expression on B cells and M phi. The functions of Fc epsilon R2 on the different cell types are not fully established and are controversial. Fc epsilon R2 on M phi, eosinophils, and platelets mediate cytotoxicity to schistosomules, enhance phagocytosis, and induce the release of granule enzymes. However, M phi from patients with atopic dermatitis expressing significantly more Fc epsilon R2 than M phi from normals do not release more leukotriene C4, prostaglandin E2, or beta-glucuronidase after incubation with aggregated IgE than normal monocytes. Furthermore, aggregated IgG1 is much more efficient than IgE in inducing mediator release from M phi and IgG1 antibodies are not known to induce immediate-type hypersensitivity reactions. Therefore, definitive proof that Fc epsilon R2 are involved in the pathogenesis of allergic disorders is still lacking. IL-4 appears to play a central role in immediate-type hypersensitivity. It induces human B cells to secrete IgE and IgG4, Ig isotypes typical for antibodies to helminthic parasites and allergens. IL-4 stimulates mast cell growth and upregulates Fc epsilon R2 expression. Interferon-gamma and IL-2 inhibit the IL-4-induced IgG4 and IgE secretion. Whether the abnormally high IgE antibody production in atopic patients is the result of overproduction of IL-4 or deficient IFN-gamma/IL-2 production is presently unknown. PMID- 2191056 TI - Fibronectin-cell interactions. AB - Fibronectins are widespread extracellular matrix and body fluid glycoproteins, capable of multiple interactions with cell surfaces and other matrix components. Their structure at a molecular level has been resolved, yet there are still many unanswered questions regarding their biologic activity in vivo. Much data suggests that fibronectins may promote extracellular matrix assembly, and cell adhesion to those matrices. However, one outstanding enigma is that fibronectins may, under different circumstances, promote both cell migration and anchorage. An analysis of the interaction of fibroblasts with proteolytically derived and purified domains of plasma fibronectin revealed that the type of adhesion and the correlated cytoskeletal organization depended on multiple interactions of fibronectin domains with the cell surface. Human dermal fibroblasts were capable of interacting with the integrin-binding domain and both heparin-binding domains of the plasma fibronectin molecule and their interactions determined the type of adhesion. The same principle was seen in a study of the ability of plasma fibronectin to promote basement membrane assembly in an endodermal cell line, PF HR9. There also, interactions of both heparin- and integrin-binding domains combined to promote the deposition of a proteoglycan, laminin, and type IV collagen-containing basement membrane matrix. The underlying conclusion from our studies is, therefore, that fibronectins may, through their different isotypes, multiple receptors, and varying interaction of one or more domains with those receptors, result in a spectrum of responses in different cell types. The molecular details of this array of biologic activities is not resolved but is the target of much current research. PMID- 2191057 TI - Epithelial polymeric immunoglobulin receptors. AB - The secretory immune system, which leads to secretion of polymeric immunoglobulins along mucosal surfaces, has not been shown to have any definite role in cutaneous immunology, although the polymeric immunoglobulin receptor, secretory component (SC), has been found in sweat glands and possibly in the epidermis. The purpose of this study is to examine normal human skin and cultured human keratinocytes for the presence of SC. Positive staining for SC was found in sections of normal human skin along the basement membrane zone with use of a polyclonal antibody to SC and focally on the surfaces of epidermal cells with use of a monoclonal antibody to SC. Granular cell-surface fluorescence of an intensity far less than that of the positive control HT 29 cells was seen when cultured human keratinocytes were stained for SC by indirect immunofluorescence (IF). Study of lysates of both HT 29 cells and HK by immunoblotting have been negative, perhaps due to destruction of the protein or loss of antigenicity during the extraction process. If human keratinocytes are capable of expression of SC, and the receptor can interact with IgA and IgM, this might be a mechanism for protection of the skin from microbial agent or foreign antigens and might be relevant to the deposition of IgA seen in certain skin diseases. PMID- 2191058 TI - The biology of the T-cell antigen receptor and its role in the skin immune system. AB - T lymphocytes play an important role in the generation, maintenance, and specificity of the skin immune response. T cells are the predominant class of lymphocytes found in the skin and moderate many of the initial immune responses, such as allergic contact and delayed-type hypersensitivity. In addition, the primary class of cutaneous lymphomas is believed to be of T-cell lineage. All of the antigen and MHC-restriction capabilities are manifested by the T-cell antigen receptor (TCR), the study of which has been the primary focus of immunologists for many years. Proper recognition of antigen and MHC-restriction by the TCR is necessary for the activation of the T cell. The analysis of the TCR has proved to be a useful tool for the diagnosis of lymphomas and the study of the normal skin immune system. Recently, TCR subset populations were found to be expressed specifically within the epidermis and have been hypothesized to be important in the maintenance of immunity in the skin immune system. In this article, we discuss the relationship of T cells to the immune system and the importance of the TCR to its function and homeostasis. PMID- 2191059 TI - PC-based training system for clinical use of a lung ventilator. AB - The intention of this work was to create a simple instrument for training in the operation of a lung ventilator and the understanding and interpretation of the lung-mechanical relationships between the flow and pressure curves produced by a ventilator in a patient's lung. The task was solved in a phragmatical way by storing respiratory curves in an 'acquisition' phase and reproducing them in the later 'stimulation' phase. The user can choose the following parameters: type of ventilation (flow control, pressure control, SIMV), inspiratory minute volume, inspiratory pressure, respiratory rate, percentage inspiratory time and PEEP. PMID- 2191060 TI - Decision support alerts for clinical laboratory and blood gas data. AB - We have designed and implemented a computerized Intensive Care Unit (ICU) decision support alerting system which analyzes all incoming laboratory and blood gas data for critically abnormal values and trends. A computerized patient data management system (HP 78709A PDMS, Hewlett-Packard Co., Waltham, MA) serving 20 Surgical ICU beds is networked to a Clinical Laboratory Information System and a blood gas computer system. The ALERTS subsystem operates on the PDMS as an automatic program triggered by the receipt of fresh laboratory data. Three types of ALERTS are detected: (1) high and low critical values, (2) calculation adjusted critical values, and (3) critical trends. Once detected, a specific ALERT message is displayed at the bottom of the patient's bedside PDMS terminal and at the central station. Over an eight month period a total of 1,515 ALERTS were detected from amongst approximately 115,000 laboratory data results transmitted to the Surgical Intensive Care Unit (SICU). Slightly over half of all ALERTS were caused by critical blood gas values. ALERTS were found to be a sensitive indicator of severity of illness: patients with one or more ALERTS suffered an ICU mortality of 9.52%, compared to 0% mortality in patients with no ALERTS. We conclude that automated laboratory data ALERTS represent a valuable decision support tool for the management of high risk ICU patients. PMID- 2191061 TI - Summary of the 10th Annual International Symposium on Computers in Critical Care, Pulmonary Medicine, and Anesthesia. PMID- 2191062 TI - Breath detection algorithm in digital computers. AB - An algorithm for the detection and delineation of breaths is described. The proposed algorithm takes into account the different, common modes of ventilation like the pressure controlled, volume controlled and patient triggered modes of ventilation. Airway flow curve is used as the basic delineator and the airway pressure and the Co2 concentration curves are used to confirm the delineation. A flow chart is also included to explain the algorithm. The detailed explanation and modifications, for additional confirmation and for the selections of constants, to check for the rise or fall of the pressure and Co2 curves, are also included. PMID- 2191063 TI - Inhibition by AZT of HIV-1 replication in acutely infected U-937 cells. AB - We studied the effect of AZT on the replication of HIV-1 in freshly and chronically infected U-937 monocytoid cells over a period of 2 months. Expression of viral antigens was monitored by indirect immunofluorescence, and viral replication was assessed by reverse transcriptase assay on virus pelleted from culture fluids. In U-937 cells not treated by AZT, viral antigens were expressed by 7 days after infection. The inclusion of a variety of concentrations of AZT in the culture medium was shown to retard virus replication in a dose-dependent fashion, although a complete inhibitory effect was not seen with any clinically attainable concentration of drug. Exposure of HIV-1-inoculated cells to AZT did not give rise to progeny virus possessing a drug-resistant phenotype. However, the study of clonal derivatives of U-937 cells revealed cellular variants with increased susceptibility to HIV-1, and against which AZT had reduced effectiveness in comparison with the parental line. No effect of AZT was seen on cells already infected by HIV-1, suggesting that this drug had no influence on viral replication in U-937 cells into which viral DNA had previously integrated. PMID- 2191064 TI - Heterogeneity in responses of human blood monocytes to granulocyte-macrophage colony-stimulating factor. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) has stimulatory effects on various monocyte functions. We examined whether all or only some blood monocytes could respond to GM-CSF. Monocytes from peripheral blood of healthy donors were separated by size into five fractions by counter-flow centrifugal elutriation (CCE). The phagocytic activities of monocytes in these fractions depended on the size of the cells. On activation by bacteria-derived stimuli, these fractions showed similar responses of production of monokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF) and cytotoxicity against allogeneic tumor cells. On treatment of these fractions with optimal concentration of GM-CSF, fractions 3, 4, and 5 showed tumoricidal activity and produced cell-associated IL-1, fraction 3 producing the most, whereas release of IL-1 and TNF in the supernatant was not observed. The cell-associated IL-1 was identified as IL-1 alpha, not IL-1 beta, by neutralizing tests with antisera against IL-1 alpha and IL-1 beta. GM-CSF also induced the proliferative and colony-forming responses of medium and large monocytes. These observations suggest that adoptive therapy with macrophage progenitor cells in peripheral blood may be useful in combination with GM-CSF for treatment of monocytopenia after chemotherapy or radiation therapy. PMID- 2191065 TI - Metchnikoff, the modern immunologist. PMID- 2191066 TI - Hepatic and adipose tissue lipogenic enzyme mRNA levels are suppressed by high fat diets in the rat. AB - Small changes in lipogenic enzyme activity induced by dietary fats of different composition may, over the long term, have significant impact on the development of obesity. We have investigated the effect of high fat diets (45% of calories as fat) on abundance of mRNA encoding fatty acid synthetase (FAS) and glycerophosphate dehydrogenase (GPDH) in male Sprague-Dawley rats. When caloric intake was equal, the relative amount of hepatic FAS mRNA was greater in rats fed a saturated compared to a polyunsaturated fat diet. This difference could not be attributed to diet-induced changes in plasma insulin concentration. However, both fat diets suppressed hepatic FAS mRNA compared to a sucrose diet. Close correlation between FAS specific activity and the relative amount of mRNA suggested that regulation was mainly at a pre-translational level. Adipose tissue FAS mRNA was suppressed by the two fat diets equally while GPDH mRNA was unaffected by dietary composition. Retroperitoneal fat pads were significantly larger in rats fed saturated compared to those fed polyunsaturated fat for 26 weeks. We concluded that dietary saturated fats fail to suppress hepatic de novo lipogenesis as effectively as polyunsaturated fats, which may have implications for the prevention of obesity in humans. PMID- 2191067 TI - Sterol effects on phospholipid biosynthesis in the yeast strain GL7. AB - Cells of the yeast sterol auxotroph GL7 were grown on either ergosterol or cholesterol to mid-logarithmic phase and total membrane fractions prepared. Activities of phospholipid biosynthetic enzymes in the two cell types were determined. The rates of phosphatidyl-ethanolamine-phosphatidyl-choline-N-methyl transferase and acyl-CoA-alpha-glycerol-3-phosphate transcylase were significantly greater in ergosterol-grown than in cholesterol-grown cells. These reactions were also inhibited by the polyene antibiotic filipin. By contrast the activities of long-chain fatty acyl-CoA synthetase, CTP-phosphatidate-cytidyl transferase, phosphatidylserine decarboxylase and of phosphatidylinositol synthetase were identical in the two (ergosterol and cholesterol) cultures and unaffected by filipin. The ergosterol effect on phosphatidyl-ethanolamine N methyl transferase was greatest in cells harvested in early log phase, intermediate in the mid-log phase cells, and not significant in stationary phase cells. PMID- 2191068 TI - The role of the Doppler in the differential diagnosis of lower extremity claudication syndromes. AB - Certain doppler procedures can be used as screening methods, and may be helpful in detecting and locating arterial occlusive disease in the patient with vertebrogenic sciatica or claudication syndromes of the lower extremities. The doppler has become popular in the office setting because it is quick, noninvasive and inexpensive. The procedures can be performed even with the simple stethoscope doppler. A review of the basic types of equipment as well as pertinent data interpretation are covered in this article. The methods applied are multisegmental pressures and audible doppler flow signals. PMID- 2191069 TI - Diagnosis of placenta previa by ultrasonography: a review at Ramathibodi Hospital. AB - From 1,000 ultrasonographic examinations reviewed there were 80 (8%) done for the exclusion of placenta previa. Only 83.6 per cent of these had complete medical records and were the subjects of this study. The most common reason for requesting ultrasonography was antepartum hemorrhage (79.1%). False-positive and false-negative of the report were 16.7 per cent and at least 4.2 per cent respectively. Based on the theory of placental migration it can be recommended that a minor degree of placenta previa diagnosed in the early stage of pregnancy does not need follow-up scanning while the diagnosis of placenta previa totalis follow-up scanning is imperative. A judicious decision in the combined usage of ultrasonography and double-set-up technique can reduce the risk of brisk bleeding and unnecessary cesarean section. PMID- 2191070 TI - Plasma fibrinogen--an independent cardiovascular risk factor. AB - Apart from being an acute phase reactant, fibrinogen appears to play an important although not widely recognized role in athero-/thrombogenesis. Arteriosclerotic diseases are associated with elevated levels of plasma fibrinogen. Strategies that lower the cardiovascular risk also lower fibrinogen levels. Virtually all accepted risk factors are associated with hyperfibrinogenaemia, while low risk populations usually have low fibrinogen levels. Epidemiological studies show that fibrinogen is a predictor of arteriosclerotic diseases. Its predictive power seems to be as high as or higher than accepted risk factors. These findings and other circumstantial, as well as experimental, evidence suggest that fibrinogen is a powerful, independent cardiovascular risk factor. PMID- 2191071 TI - Long-term nopharmacological treatment for mild to moderate hypertension. AB - Ninety-one middle-aged men and women with untreated mild hypertension were allocated to a nopharmacological treatment group or to a control group. Members of the treatment group were instructed to reduce daily sodium intake to less than 70 mmol, to reduce the intake of saturated fat, to lose weight if necessary and to perform regular physical exercise and relaxation training. Adherence to and effects of the programme on blood pressure and serum lipids were monitored for 12 months. In the treatment group, daily sodium excretion decreased to and remained at 50% of its original level (P less than 0.001), and there was a significant reduction in saturated fat intake. The average weight reduction was modest. Adherence to physical exercise and relaxation training regimens was poor. The net decreases (difference in changes between treatment and control group) in blood pressure were greatest during the first 3 months: in men the decrease in systolic blood pressure was 11.3 mmHg (P less than 0.001) and in diastolic blood pressure 8.3 mmHg (P less than 0.001); in women the decrease in systolic blood pressure was 10.8 mmHg (P less than 0.01) and in diastolic blood pressure 6.4 mmHg (P less than 0.01). However, this decrease diminished during the last 3 months to approximately one half owing to blood pressure reduction in controls. Low density lipoprotein cholesterol levels decreased significantly in treated men and women. PMID- 2191072 TI - Characterization of the tissue macrophage and the interstitial dendritic cell as distinct leukocytes normally resident in the connective tissue of rat heart. AB - Immunohistological studies with a mouse anti-rat macrophage mAb (BMAC-5) demonstrated the presence of numerous positive cells in the interstitial connective tissues of many organs. The pattern resembled that seen with anti-MHC class II antibodies, with the striking exception that BMAC-5+ cells were rare or absent in the portal triad, the islets of Langerhans, and the kidney. Double labeling fluorescence studies were therefore performed in rat heart using the BMAC-5 mAb in combination with rabbit antisera to pure rat class II MHC antigens and pure rat leukocyte common (CD45) antigens. The tissue macrophages in heart were identified as BMAC-5+, MHC class II-negative, leukocyte common antigen positive cells. They could be distinguished from the BMAC-5-, MHC class II positive, leukocyte common antigen-positive interstitial dendritic cells. Moreover, 7 d after lethal irradiation, the class II-positive interstitial dendritic cells had completely disappeared from heart, whereas the BMAC-5+ macrophages were present in undiminished numbers. These studies strongly suggest that the interstitial dendritic cell and the tissue macrophage represent two distinct populations of leukocytes within the connective tissues of antigenically secluded organs such as the heart. They have potentially important implications for the physiology of the immune system, as well as for autoimmunity and transplantation. PMID- 2191073 TI - Hyaluronic acid accumulation and redistribution in rejecting rat kidney graft. Relationship to the transplantation edema. AB - By using biotin-labeled proteoglycan core protein and an avidin-enzyme system, hyaluronic acid (HA) was visualized in rat kidney. In the normal kidney, HA was localized in the extracellular space of the inner medulla and increased markedly towards the papillary tip. No staining for HA was seen in the interstitial tissue of the cortex or the outer medulla. During the development of rejection of allogeneic renal grafts, a progressive increase in accumulated HA was seen in the interstitial tissue of the cortex and outer medulla. The extractable amounts of HA increased, on average, 40 times in the cortex and outer medulla; no increase was measured in the inner medulla and papilla. The relative water content of the cortex and outer medulla also increased progressively and correlated with the HA accumulation. The extractable amounts of HA in syngeneic grafts increased by day 2 and then leveled off, indicating that surgical trauma may induce some transient HA accumulation after transplantation. Interstitial accumulation of HA, a glycosaminoglycan with unique water-binding qualities, would presumably influence water transport and osmotic activity and should thereby be implicated in the normal papillary function, but also in the development of the interstitial edema of the cortex and outer medulla during rejection of renal grafts. PMID- 2191074 TI - Viruses as therapeutic agents. II. Viral reassortants map prevention of insulin dependent diabetes mellitus to the small RNA of lymphocytic choriomeningitis virus. AB - Nonobese diabetic (NOD) mice are the experimental prototype of type 1 insulin dependent diabetes mellitus (IDDM). These mice develop a characteristic autoimmune lesion in the pancreatic islets of Langerhans, where infiltrating lymphocytes destroy beta cells, resulting in hypoinsulinemia, hyperglycemia, ketoacidosis, and death. This IDDM, which closely resembles that in humans, is prevented by infecting NOD mice with particular strains of lymphocytic choriomeningitis virus (LCMV), including Armstrong 53b, Traub, WE, and Pasteur. In contrast, the LCMV Armstrong 53b variant, Clone 13, fails to abort IDDM. Hence, although Clone 13 establishes a persistent infection that endures throughout the life spans of NOD mice, their hyperglycemia, hypoinsulinemia, and lymphocytic infiltration into the islets of Langerhans still occur. Genetic reassortant viruses generated between the IDDM therapeutic strain of LCMV Pasteur and the nontherapeutic variant, LCMV Clone 13, were used to treat NOD mice. By using such reassortants and both parental strains of virus to infect NOD mice, the prevention of IDDM was mapped to the S RNA segment of LCMV Pasteur. PMID- 2191075 TI - Confused and befuddled am I. PMID- 2191076 TI - The purification, characterization and role of the d-type cytochrome oxidase of Klebsiella pneumoniae during nitrogen fixation. AB - Klebsiella pneumoniae synthesized only b-type and d-type cytochromes under the wide range of growth conditions tested, and reaction with CO revealed two potential oxidases. The o-type oxidase was produced only in the presence of O2 and appeared to be repressed by glucose. The d-type oxidase was, by contrast, produced only in the absence of measurable O2 (less than 1 microM), and was the only oxidase expressed in nitrogen-fixing conditions. It was extracted from the membrane, purified and shown to be similar to that from E. coli in being a heterodimer (subunits of Mr 52,000 and 35,000), in containing two distinguishable b haems and haem d (one or two molecules per molecule of oxidase), and in being able to react with O2 to give a stable oxygenated intermediate. The purified d type cytochrome oxidase had a very high affinity for O2 (Km 20 nM; measured by the spectral properties of leghaemoglobin). It is proposed that this provides a role for this oxidase in lowering the O2 concentration to allow nitrogenase synthesis and function, and to provide a terminal oxidase to permit electron transport-coupled ATP synthesis which supports the increase in efficiency of nitrogen fixation observed under microaerobic conditions. PMID- 2191077 TI - Biosynthesis and scavenging of pyrimidines by pathogenic mycobacteria. AB - Mycobacterium microti incorporated a wide range of exogenously supplied pyrimidines into its nucleic acids. M. avium incorporated a relatively narrow range of pyrimidines but both M. avium and M. microti when recovered after growth in vivo incorporated a slightly wider range of pyrimidines than the same strains grown in vitro. M. microti and M. leprae could not take up uridine nucleotides directly but could utilize the pyrimidines by hydrolysing them to uridine and then taking up the uridine. Pyrimidine biosynthesis, judged by the ability to incorporate carbon from CO2 or aspartate into pyrimidines was readily detected in non-growing suspensions of M. microti and M. avium harvested from Dubos medium, which does not contain pyrimidines. The biosynthetic activity was diminished in mycobacteria grown in vivo when there is likely to be a source of pyrimidines which they might use. Relative activities for pyrimidine biosynthesis de novo in M. microti were 100 for cells isolated from Dubos medium, 6 for cells isolated from Dubos medium containing the pyrimidine cytidine and 11 from cells recovered after growth in mice. In contrast, relative activities for a scavenging reaction, uracil incorporation, were 100, 71 and 59, respectively. Three key enzymes in the pathway of pyrimidine biosynthesis de novo were detected in M. microti and M. avium. Two, dihydroorotate synthase and orotate phosphoribosyltransferase appeared to be constitutive in M. microti and M. avium. Aspartate transcarbamoylase activity was higher in these mycobacteria grown in vivo than in Dubos medium but it was repressed in M. microti or M. avium grown in Dubos medium in the presence of 50 microM-pyrimidine. Aspartate transcarbamoylase was strongly inhibited by the feedback inhibitors ATP, CTP and UTP. Enzymes for scavenging pyrimidines were detected at low specific activities in all mycobacteria studied. Activities of phosphoribosyltransferases, enzymes that convert bases directly to nucleotides, were not related to the ability of intact mycobacteria to take up pyrimidine bases while activities of pyrimidine nucleoside kinases were generally related to the ability of intact mycobacteria to take up nucleosides. Phosphoribosyltransferase activity for uracil, cytosine, orotic acid and--in organisms grown in Dubos medium with 50 microM-uridine-thymine, as well as kinases for uridine, deoxyuridine, cytidine and thymidine were detected in M. microti. However, M. avium only contained uracil and orotate phosphoribosyltransferase, uridine, cytidine and thymidine kinase, and additionally deoxyuridine kinase when grown axenically with 50 microM-uracil, reflecting its more limited abilities in pyrimidine scavenging. PMID- 2191078 TI - Aspartate metabolism in Mycobacterium avium grown in host tissue and axenically and in Mycobacterium leprae. AB - Aspartokinase activity was detected in extracts from Mycobacterium leprae (recovered from armadillo liver) and in Mycobacterium avium grown axenically and in vivo. Homoserine dehydrogenase activity was only detected in M. leprae and in M. avium grown axenically. Activities, when detected, were 50 to 70% lower in M. leprae or M. avium grown in vivo than in axenically grown M. avium. In these two pathogenic mycobacteria, aspartokinase and homoserine dehydrogenase are subject to feedback inhibition by methionine - an additional regulator over those observed for the enzymes from Mycobacterium smegmatis. Intact mycobacterium incorporated carbon from [U-14C]aspartate into the aspartate family of amino acids (threonine, isoleucine, methionine and lysine) though the rate of incorporation in M. avium grown in vivo was about half that in M. avium grown axenically. PMID- 2191079 TI - Enzymes for biosynthesis de novo and elongation of fatty acids in mycobacteria grown in host cells: is Mycobacterium leprae competent in fatty acid biosynthesis? AB - Fatty acid synthetase activity in extracts of Mycobacterium leprae was equivalent to 1.7 pmol malonyl-CoA incorporated into fatty acid min-1 (mg protein)-1. This activity--if representative of living M. leprae organisms--is insufficient to enable them to synthesize their lipid requirements rapidly enough to support growth. The major activity for scavenging fatty acids in extracts of Mycobacterium microti and Mycobacterium avium, as well as in extracts of M. leprae, was acetyl-CoA-dependent fatty acyl-CoA 'elongase'. This activity was about four times higher in M. avium and M. microti grown in a medium which contained lipids, or when grown in mice, than in medium without added lipids. In contrast, the de novo fatty acid synthetase activity was repressed in M. avium and M. microti when grown in medium that contained lipids, or when grown in mice. These results are consistent with the hypothesis that mycobacteria grown in vivo preferentially scavenge lipids from the host cells, and suggest that a source of lipid should be included in media for attempted axenic isolation of M. leprae. PMID- 2191080 TI - Stable albicidin resistance in Escherichia coli involves an altered outer membrane nucleoside uptake system. AB - Albicidin blocked DNA synthesis in intact cells of a PolA- EndA- Escherichia coli strain, and in permeabilized cells supplied with all necessary precursor nucleotides, indicating a direct effect on prokaryote DNA replication. Replication of phages T4 and T7 was also blocked by albicidin in albicidin sensitive (Albs) but not in albicidin-resistant (Albr) E. coli host-cells. All stable spontaneous Albr mutants of E. coli simultaneously became resistant to phage T6. The locus determining albicidin sensitivity mapped at tsx, the structural gene for an outer-membrane protein used as a receptor by phage T6 and involved in transport through the outer membrane of nucleosides present at submicromolar extracellular concentrations. Albicidin does not closely resemble a nucleoside in structure. However, Albs E. coli strains rapidly accumulated both nucleosides and albicidin from the surrounding medium whereas the Albr mutants were defective in uptake of nucleosides and albicidin at low extracellular concentrations. An insertion mutation blocking Tsx protein production also blocked albicidin uptake and conveyed albicidin resistance. Albicidin supplied at approximately 0.1 microM blocked DNA replication within seconds in intact Albs E. coli cells, but a 100-fold higher albicidin concentration was necessary for a rapid inhibition of DNA replication in permeabilized cells. We conclude that albicidin is effective at very low concentrations against E. coli because it is rapidly concentrated within cells by illicit transport through the tsx-encoded outer-membrane channel normally involved in nucleoside uptake. Albicidin resistance results from loss of the mechanism of albicidin transport through the outer membrane. PMID- 2191081 TI - RecA-independent high-frequency deletion of recombinant cosmid DNA in Escherichia coli. AB - Segments of DNA were deleted from recombinant cosmid DNAs during propagation in Escherichia coli hosts in liquid culture. DNAs of more than 1000 cosmids propagated in various E. coli hosts were analysed by agarose gel electrophoresis (AGE). The effects of vectors, insert DNAs and host genetic characters on the formation of deletions were examined. The probability of deletion and the pattern of deletion bands observed by AGE differed from clone to clone, and after extensive culture the deletion band patterns remained almost constant during further culture. Most recombinant clones eventually showed deletion during prolonged liquid culture. Mutations in the recA gene of E. coli hosts, including a deletion mutation, did not prevent deletion. Most deletions occurred in the insert portions of cosmid DNAs. Nucleotide sequence analysis of six deletion junctions in test cosmid cMB15 demonstrated that deletions occurred between two short complete direct repeats of about 4-10 bp, irrespective of whether the cosmid was propagated in a recA host or a rec+ host. Some deletions occurred at the same sites either in a recA host or a rec+ host. These results suggest that the deletion events are mainly mediated by a recA-independent recombination system(s) of E. coli host cells. PMID- 2191082 TI - A new potexvirus associated with strawberry mild yellow edge disease. AB - A physical map of cDNA clones prepared from dsRNA associated with the MY-18 source of strawberry mild yellow edge (SMYE) was constructed and 854 nucleotides adjacent to the 3' poly(A) tail were sequenced. The larger open reading frame product of Mr 25714 showed considerable amino acid homology to the coat protein cistrons of six potexviruses and two carlaviruses. A second product of Mr 11216 encoded completely within the coat protein cistron, but in a different frame, has similarities to two potexvirus polypeptides. The Mr 25714 ORF was fused to the Protein A gene in an expression vector and the fusion protein was purified by affinity chromatography and used to immunize a rabbit. The resulting polyclonal antiserum reacted strongly in immunoelectron microscopical tests with filamentous particles resembling those of potexviruses. Such particles were detected in the following SMYE sources: D-74 from Germany, two from the United Kingdom in Fragaria vesca 'Alpine' indicator plants and Oregon MY-18 in Rubus rosifolius. Among 27 potexvirus antisera tested for serological reactions none yielded strong decoration. Examination of ultrathin sections of R. rosifolius and F. vesca tissue infected with SMYE revealed aggregates of filamentous particles in phloem parenchyma cells. dsRNA from nine sources of SMYE collected from around the world reacted with the cDNA clones of this potexvirus in Northern hybridizations. It is concluded that the potexvirus is hitherto undescribed and the name strawberry mild yellow edge-associated potexvirus is proposed. PMID- 2191084 TI - The occult aftermath of boxing. AB - The repeated head trauma experienced by boxers can lead to the development of dementia pugilistica (DP)--punch drunk syndrome. The neuropathology of DP in a classic report by Corsellis et al describes the presence of numerous neurofibrillary tangles in the absence of plaques, in contrast to the profusion of tangles and plaques seen in Alzheimer's disease (AD). The DP cases used in that report were re-investigated with immunocytochemical methods and an antibody raised to the beta-protein present in AD plaques. We found that all DP cases with substantial tangle formation showed evidence of extensive beta-protein immunoreactive deposits (plaques). These diffuse "plaques" were not visible with Congo-red or standard silver stains. The degree of beta-protein deposition was comparable to that seen in AD. Our data indicate that the present neuropathological description of DP (tangles but no plaques) should be altered to acknowledge the presence of substantial beta-protein deposition (plaques). The molecular markers present in the plaques and tangles of DP are the same as those in AD. Similarities in clinical symptoms, distribution of pathology and neurochemical deficits also exist. Epidemiological studies have shown that head injury is a risk factor in AD. It is probable that DP and AD share common pathogenic mechanisms leading to tangle and plaque formation. PMID- 2191083 TI - The diagnosis of subarachnoid haemorrhage. PMID- 2191085 TI - Stereotaxic thalamotomy--experiences from the levodopa era. AB - After the introduction of levodopa drugs in the late 1960s, the number of thalamotomies fell dramatically world wide. However, as the Parkinsonian tremor proved rather resistant to levodopa treatment, the interest in this operation has been reviewed. During 1978-86, 51 stereotaxic thalamotomies were performed in 48 patient in our department. Thirty three of these patients had Parkinsonism, nine multiple sclerosis (MS) and the remaining six had various other involuntary movement disorders. The operation was most useful in the Parkinsonian group. Nearly 80% of these patients gained a substantial benefit in their daily lives. Patients with MS were all in advanced stages of the disease, and the operation was tried as a last resort. They had less benefit and more complications from operation than the other patients. PMID- 2191086 TI - Distribution of DARPP-32 in the basal ganglia: an electron microscopic study. AB - DARPP-32, a dopamine and cyclic AMP-regulated phosphoprotein, has been studied by light and electron microscopical immunocytochemistry in the rat caudatoputamen, globus pallidus and substantia nigra. In the caudatoputamen, DARPP-32 was present in neurons of the medium-sized spiny type. Immunoreactivity for DARPP-32 was present in dendritic spines, dendrites, perikaryal cytoplasm, most but not all nuclei, axons and a small number of axon terminals. Immunoreactive axon terminals in the caudatoputamen formed symmetrical synapses with immunolabeled dendritic shafts or somata. Neurons having indented nuclei were never immunoreactive. In the globus pallidus and substantia nigra pars reticulata, DARPP-32 was present in myelinated and unmyelinated axons and in axon terminals. The labelled axon terminals in these regions formed symmetrical synaptic contacts on unlabelled dendritic shafts or on unlabelled somata. These data suggest that DARPP-32 is present in striatal neurons of the medium-sized spiny type and that these DARPP 32-immunoreactive neurons form symmetrical synapses on target neurons in the globus pallidus and substantia nigra. The presence of DARPP-32 in these striatal neurons and in their axon terminals suggests that DARPP-32 mediates part of the response of medium-size spiny neurons in the striatum to dopamine D-1 receptor activation. PMID- 2191087 TI - Electrocardiographic monitoring: an overview. AB - This article presents an overview of the key principles and methods underlying modern electrocardiographic (ECG) monitoring. Multilead processing, improved noise reduction techniques, and automatic lead-fail detection substantially enhance the reliability of ECG monitoring today. Computerized ECG signal processing provides reliable automatic arrhythmia detection, based on sophisticated waveform recognition and classification schemes. State-of-the-art ECG monitors carry out automatic ST segment analysis. They also detect and process pacemaker signals. A variety of signal-processing methods are described. PMID- 2191088 TI - Commercial double-indicator-dilution densitometer using heavy water: evaluation in oleic-acid pulmonary edema. AB - We evaluated a commercially available, double-indicator-dilution densitometric system for the estimation of pulmonary extravascular water volume in oleic acid induced pulmonary edema. Indocyanine green and heavy water were used as the nondiffusible and diffusible tracers, respectively. Pulmonary extravascular water volume, measured with this system, was 67% of the gravimetric value (r = 0.91), which was consistent with values obtained from the radioisotope methods. The measured volume was not influenced by changes in cardiac index over a range of 1 to 4 L.min.m2. This system is less invasive than the thermal-dye technique and has potential for repeated clinical measurements of pulmonary extravascular lung water and cardiac output. PMID- 2191089 TI - Cerebral sparganosis. Case report. AB - The tapeworm Spirometra mansonoides infects man worldwide, particularly in Asian countries. Rarely, the central nervous system is involved; such a case is presented here. In the total of 12 reported cases, including the case described, the worm presented clinically as a mass suspicious for neoplasm or chronic abscess cavity. Surgical removal was invariably curative in each case. Although infrequent, the possibility of tapeworm infection should be entertained in the evaluation of intracranial masses in patients who have visited exotic locales. PMID- 2191090 TI - The International Cooperative Study on the Timing of Aneurysm Surgery. Part 1: Overall management results. AB - The International Cooperative Study on the Timing of Aneurysm Surgery evaluated the results of surgical and medical management in 3521 patients between December, 1980, and July, 1983. At admission, 75% of patients were in good neurological condition and surgery was performed in 83%. At the 6-month evaluation, 26% of the patients had died and 58% exhibited a complete recovery. Vasospasm and rebleeding were the leading causes of morbidity and mortality in addition to the initial bleed. Predictors for mortality included the patient's decreased level of consciousness and increased age, thickness of the subarachnoid hemorrhage clot on computerized tomography, elevated blood pressure, preexisting medical illnesses, and basilar aneurysms. The results presented here document the status of management in the 1980's. PMID- 2191091 TI - The International Cooperative Study on the Timing of Aneurysm Surgery. Part 2: Surgical results. AB - A prospective, observational clinical trial was conducted by the International Cooperative Study on the Timing of Aneurysm Surgery to determine the best time in relation to the hemorrhage for surgical treatment of ruptured intracranial aneurysms. Sixty-eight centers contributed 3521 patients in a 2 1/2-year period beginning in December, 1980. Analysis by a prespecified "planned" surgery interval demonstrated that there was no difference in early (0 to 3 days after the bleed) or late surgery (11 to 14 days). Outcome was worse if surgery was performed in the 7 to 10-day post-bleed interval. Surgical results were better for patients operated on after 10 days. Patients alert on admission fared best; however, alert patients had a mortality rate of 10% to 12% when undergoing surgery prior to Day 11 compared with 3% to 5% when surgery was performed after Day 10. Patients drowsy on admission had a 21% to 25% mortality rate when operated on up to Day 11 and 7% to 10% with surgery thereafter. Overall, early surgery was neither more hazardous nor beneficial than delayed surgery. The postoperative risk following early surgery is equivalent to the risk of rebleeding and vasospasm in patients waiting for delayed surgery. PMID- 2191092 TI - Correlation of transcranial Doppler sonography findings with timing of aneurysm surgery. AB - Thirty-six patients with a proven first subarachnoid hemorrhage (SAH) from a ruptured supratentorial aneurysm were subjected to repeated transcranial Doppler sonography assessments. Eighteen individuals (Group A) were operated on within 48 hours, while the other 18 (Group B) had surgery between 49 and 96 hours after SAH. The patients represented two clinically comparable groups. In the first 72 hours post-SAH, no increased flow velocities suggestive of arterial narrowing or vasospasm were recorded. There was no significant difference in preoperative flow velocities between the groups. Postoperative flow velocities were significantly lower in patients operated on within 48 hours (p less than 0.001). Two patients, who had surgery on Day 4 post-SAH and who showed the highest recorded postoperative flow velocities, died from cerebral vasospasm and infarction. The results favor a referral system which enables early surgical intervention not only to prevent rebleeds but also aimed at reducing delayed ischemic dysfunction. PMID- 2191093 TI - Effect of age and diet on glucose tolerance in Sprague-Dawley rats. AB - Male Sprague-Dawley rats ages 12 and 27 mo were used to evaluate intravenous glucose tolerance. Rats were fed ad libitum a purified diet containing either 33% sucrose and 33% starch or 66% starch, 17.5% casein and 7% fat (g/100 g) for 4 mo. Each animal was fitted with a cannula in the left carotid artery while anesthetized with methoxyflurane and was allowed to recover without food for 10 12 h. A resting blood sample was withdrawn, and then each rat received 1 mL of 50% glucose in saline per kilogram body weight throughout the carotid cannula. The cannula was washed with the rat's blood to remove any excess glucose, and blood samples were taken at 5, 10, 15, 30, 45 and 60 min after infusion. The 12 mo-old rats in both the high sucrose and sucrose-free diet groups had significantly greater resting plasma glucose and insulin concentrations than did their 27-mo-old counterparts. Diet had no effect on resting glucose or insulin levels. Neither age nor diet had a significant effect on plasma glucose or insulin concentrations following the glucose infusion. These data suggest that the pancreatic response to a glucose load is not altered by age or high sucrose diets. PMID- 2191094 TI - Ionophores and nutrient digestion and absorption in ruminants. AB - This paper reviews the effects of feeding ionophores on nutrient digestion and absorption. In cattle, monensin and lasalocid increase apparent digestible energy by an average of 2.0 percentage units. In sheep, responses in digestible energy to ionophore feeding have been more variable, and neither monensin nor lasalocid have, on average, affected digestible energy. The effect of ionophores on fiber digestibility appears to depend on diet composition and source of fiber because both increases and decreases in fiber digestibility have been associated with ionophore feeding. Lasalocid and monensin reduce the percentage of starch digested in the rumen and increase the quantity of starch digested in the intestine. However, total gastrointestinal tract digestion of starch has generally not been affected by ionophores. Apparent nitrogen digestibility has been increased by ionophore feeding in a number of animal species. Apparent absorption of magnesium, phosphorus, zinc and selenium has been increased by ionophore supplementation. Absorption of calcium, potassium and sodium has been inconsistently affected by ionophores. Possible mechanisms whereby ionophores may affect nutrient digestion and absorption are discussed. PMID- 2191095 TI - Manipulation of the functional activity of the gut by dietary and other means (antibiotics/probiotics) in ruminants. AB - The mucosa of the gut is some of the most metabolically active tissue in the body. This paper discusses the methodology used to assess enterocyte cell metabolism and nutrient uptake in the reticulorumen and small intestine of ruminant species. Metabolism of volatile fatty acids and glucose by this tissue may limit the availability of essential nutrients to peripheral tissues, and the extent to which this may vary between concentrate-based and forage-based diets is discussed. Factors that affect the development and expression of metabolite uptake by the enterocyte are considered in addition to the influence that manipulation of the microbial flora of the gut by the use of antibiotic growth promoters or probiotics may have upon this process. Data are presented to show that the use of antibiotic compounds in ruminant feeds can influence the rate of cell turnover in the small intestine and the rate of glucose uptake by isolated brush border vesicles. PMID- 2191096 TI - Changes in liver and gastrointestinal tract energy demands in response to physiological workload in ruminants. AB - Liver and gastrointestinal tract weights (ingesta- and adipose-free) appear to increase or decrease in direct proportion to dietary intake within and across physiological stages of maintenance, growth, fattening or lactation. Liver and gut mass increase approximately 15 and 30 g per unit of liveweight raised to the 0.75 power (Wt0.75) for each multiple of 500 kJ/Wt0.75 [approximately 1 x maintenance (M)] increase in metabolizable energy (ME) intake, with linearity indicated up to the highest recorded level (4.5 x M). Extrapolation from in vivo arteriovenous O2 measurements across splanchnic tissues and from the previously cited weight information indicates that liver and gut tissue oxidize approximately 3.5 and 1.0 kJ of ME/g of fresh tissue daily, in contrast to whole animal rates of 0.1 kJ/g. Thus, energy use by the relatively small amount of liver and gut accounts for 45 to 50% of whole-animal heat energy. On a differential basis, increases in energy use by these tissues appear to account for up to 70% of the heat increment of ME use above maintenance. PMID- 2191097 TI - Unusual causes of renal failure in diabetics: two case studies. AB - An atypical course of diabetic nephropathy may signal an associated glomerulonephritis or other complicating illness. Two cases illustrate the importance of seeking reversible causes of renal dysfunction in diabetics. PMID- 2191099 TI - Novel and sensitive noncompetitive (two-site) enzyme immunoassay for haptens with amino groups. AB - A novel and sensitive noncompetitive (two-site) enzyme immunoassay for haptens with amino groups is described. L-Thyroxine (T4) was used as a model hapten. T4 was indirectly biotinylated with glutathione as spacer between T4 and biotin molecules and trapped onto anti-(T4-bovine serum albumin) IgG-coated polystyrene balls. After washing the polystyrene balls to eliminate unreacted biotin and other biotinylated substances, biotinylated T4 was eluted from the polystyrene balls with HCl and was reacted with anti-(T4-bovine serum albumin) Fab' horseradish peroxidase conjugate. The complex formed was trapped onto streptavidin-coated polystyrene balls. Peroxidase activity bound to the polystyrene balls was assayed by fluorimetry. The detection limit of T4 was 78 fg (0.1 fmol)/tube, which was 50-fold lower than the limit by competitive enzyme immunoassay using the same antibody and T4-peroxidase conjugate. This noncompetitive enzyme immunoassay was applied to the measurement of total T4 in serum. Serum levels of total T4 in 10 healthy subjects aged 25-40 yr were 94 +/- 13 (SD) micrograms/L (range, 78-114). The principle of this noncompetitive enzyme immunoassay may allow it to measure other haptens with amino groups more sensitively than can competitive immunoassays. PMID- 2191098 TI - [Detection of immunoglobulin in the inner ear tissue by PAP method]. AB - The distribution of immunoglobulins IgG, IgA and IgM in the inner ear tissue from a patient who died of lung bleeding followed after sepsis was studied, and also the normal guinea pig inner ears and the inner ear disorders induced by Kanamycin injection were studied for the distribution of IgG. The temporal bones were fixed in formaldehyde, decalcified in EDTA and embedded in paraffin. The PAP method was used for the demonstration of the immunoglobulins. In both the human inner ear tissue and the normal control inner ear tissue of the guinea pigs deposits of IgG were found in the sensory organs and the endolymphatic sac, however, in the stria vascularis was slight. The severe damaged inner ears induced by Kanamycin the remarkable decreased deposits of IgG were found in the cochlea, but in the endolymphatic sac the remarkable increased deposits of IgG were found. No IgA and IgM were found in the human inner ear tissue. PMID- 2191100 TI - Sensitive time-resolved fluorimetric immune-complex-transfer immunoassay for antithyroglobulin IgG in serum. AB - A sensitive time-resolved fluorimetric immune-complex-transfer immunoassay for antithyroglobulin IgG in serum is described. Antithyroglobulin IgG in test serum was reacted with dinitrophenyl europium ion-labeled thyroglobulin. The complex formed of antithyroglobulin IgG and dinitrophenyl europium ion-labeled thyroglobulin was trapped onto two polystyrene balls coated with affinity purified rabbit antidinitrophenyl bovine serum albumin IgG. The polystyrene balls were washed to eliminate nonspecific IgG in the test serum, and the complex was eluted from the polystyrene balls with dinitrophenyl-L-lysine and transferred to two polystyrene balls coated with affinity-purified rabbit antihuman IgG gamma chain IgG. Europium ion bound to the polystyrene balls was measured by time resolved fluorimetry. Antithyroglobulin IgG was demonstrated in all patients with Graves' disease and all patients with chronic thyroiditis. This immunoassay was more sensitive than the conventional enzyme immunoassay and less time-consuming than the previously described immune-complex-transfer enzyme immunoassays, although there were larger assay variations. PMID- 2191101 TI - Cardiolipin liposomes: a novel flow reagent for detection of anticardiolipin antibodies. AB - The association of autoantibodies with specificity for phospholipids and an increased risk for thromboembolic phenomena has received considerable recent clinical attention. These autoantibodies have been reported in patients with defined autoimmune disorders as well as in patients with no other obvious autoimmune disease symptoms other than isolated or recurrent thromboembolic disease. A significant component of this autoimmune response appears to be related to cardiolipin-directed antibodies. Most studies reported to date have used either an enzyme immunoassay or a radioimmunoassay for detection and quantitation of antiphospholipid antibodies. We have developed a novel flow cytometric assay for detection of anticardiolipin antibodies. The assay, by analogy to polystyrene microsphere assay, utilizes cardiolipin liposomes as solid phase microspheres for antigen presentation. In comparison to enzyme-linked immunosorbent assay, the flow assay shows similar sensitivity by serum titration, has immunoglobulin class specificity, and is semiquantitative as currently designed. The flow assay is relatively easy to perform and should allow detection of other antiphospholipid specificities with tailoring of the phospholipid makeup of the liposomes. PMID- 2191102 TI - MISET: an immunological technique for the serodiagnosis of Cryptobia salmositica (Sarcomastigophora: Kinetoplastida) infection in Oncorhynchus mykiss. AB - A serodiagnostic technique, microscopic immuno-substrate-enzyme technique (MISET), is described using the Cryptobia-Oncorhynchus mykiss system. The reactions of specific antibodies, phosphatase-labeled antibody, and substrate with subsequent color development on the parasite (cell membrane, flagella, kinetoplast, and nucleus) are observed using light microscopy. Using this technique, humoral response to Cryptobia salmositica was detected in 2 of 10 O. mykiss 7 days after infection. Subsequently, antibodies were detected in all 10 infected fish. Parasites cultured in minimum essential medium or from experimentally infected pink salmon, Oncorhynchus gobuscha, worked equally well. Antibodies eluted from antisera or whole blood dried on filter paper (stored at 20 C) gave similar reactions as those from antisera stored in containers. MISET is at least as sensitive as the indirect fluorescent antibody technique. When MISET is modified and adapted for other parasitic diseases (e.g., for those of medical and or of economic importance), it may be useful especially in smaller centers or in developing countries where equipment cost, maintenance of equipment, operating costs, and well trained personnel are important considerations. Because MISET worked with dried whole blood or serum on filter paper it may also be a useful field technique for large scale seroepidemiological surveys. PMID- 2191103 TI - Effects of murine giardiasis on growth, intestinal morphology , and disaccharidase activity. AB - The aim of this study was to assess the effects of Giardia muris on host growth and food intake, small intestinal morphometrics, mucosal enzyme activities, and brush border ultrastructure. Weanling mice infected with 1,000 G. muris cysts were compared to control and pair-fed sham-treated animals. Infection with G. muris resulted in decreased food intake and retarded growth. In infected animals, villus atrophy was observed in the duodenum throughout the study period and in the jejunum on days 8 and 50. On day 30, whereas jejunal architecture returned to normal in infected animals, malnourished pair-fed animals exhibited a compensatory increase in villus height. Sucrase and maltase were depressed in infected animals on days 2-24. On day 8 jejunal disaccharidases in pair-fed animals were also decreased but to a lesser extent than in infected animals. On day 24, disaccharidase values for control and infected mice were similar, whereas values in pair-fed animals were increased. On day 8, jejunal microvilli were shorter in infected animals than in control and pair-fed animals. This brush border injury was present throughout the jejunum and was also observed in pair fed animals, but to a lesser extent. These findings suggest that G. muris retards growth in weanling mice, results in small intestinal injury, and interferes with the compensatory response to malnutrition of the infected host. Villus atrophy and brush border enzyme deficiencies associated with the disease mainly occur in the duodenum and jejunum, where trophozoites are most numerous. In infected and in pair-fed animals, the decrease in jejunal disaccharidase activities correlated with a diffuse shortening of brush border microvilli. PMID- 2191104 TI - Anatomical distribution of developing trophozoites and schizonts of Plasmodium vivax in Aotus lemurinus lemurinus and Saimiri sciureus. AB - Organ distribution of developing trophozoite- and schizont-infected erythrocytes of Plasmodium vivax and night monkeys, Aotus lemurinus lemurinus, and squirrel monkeys, Saimiri sciureus, was determined. The primary site for the infection in both species was the splenic vasculature. Secondary organ involvement differed between hosts although some overlapping did occur. PMID- 2191105 TI - The rarity of asexual reproduction among Mesocestoides tetrathyridia (Cestoda). PMID- 2191106 TI - The effects of anesthesia and surgery on metabolic homeostasis in infancy and childhood. AB - In order to test the hypothesis that the metabolic response to surgery in childhood varies with the age of the child and the severity of the surgery, 46 children, aged 1 month to 10 years and undergoing a variety of operations under a standard general anesthetic, were studied. Blood samples were drawn for analysis preoperatively, postoperatively, and at 6, 12, 24, and 48 hours after surgery. Severity of surgery was scored using the Oxford surgical stress scale (SSS). Surgery caused significant increases in the concentrations of lactate, pyruvate, and ketone bodies that were related to SSS, but not to age. Increases in blood glucose and insulin were also related to SSS. Total gluconeogenic substrate concentrations were markedly depressed 24 hours after surgery; this was well predicted by SSS but not by age. Older children tended to have a slightly more prolonged elevation of blood glucose and prolonged elevation of the insulin:glucose ratio postoperatively. The metabolic response of children to surgery, although different from both adults and neonates, is generally stable over a wide age range. The Oxford scale predicts the degree of metabolic displacement due to surgery and may thus prove a useful instrument in trials of anesthesia and analgesia in infants and children. PMID- 2191107 TI - Pathophysiology of congenital diaphragmatic hernia: I. Renal enlargement suggests feedback modulation by pulmonary derived renotropins--a unifying hypothesis to explain pulmonary hypoplasia, polyhydramnios, and renal enlargement in the fetus/newborn with congenital diaphragmatic hernia. AB - Survival of newborns with congenital diaphragmatic hernia (CDH) is largely dependent on the severity of pulmonary hypoplasia (PH) present at birth. Intrathoracic compression by the herniated abdominal viscera is thought to be the primary factor involved in the pathogenesis of the PH in CDH. Humoral and/or amniotic pulmonary growth factors (PGF) have been hypothesized to play a role in normal fetal pulmonary development and may be involved in the pathogenesis of CDH as well. The hypothesis of this paper is that growth of the fetal lung is stimulated by a PGF produced by the kidneys, which is modulated by a feedback signal from the lungs, a pulmonary derived renotropin (PDR). In the fetus with CDH, the lungs may be unable to respond to PGF due to compression by the herniated abdominal viscera. Theoretically, PH associated with CDH would maximally stimulate this feedback loop to release more PDR, resulting in continual stimulation of the kidneys and renal enlargement. If such a scheme plays a role in the in utero pathophysiology of CDH, then newborns with CDH should have enlarged kidneys. To investigate this hypothesis, we reviewed 30 autopsy cases of newborns with CDH and analyzed their kidney weights versus body weights, using historical data as control. Kidney weights in CDH cases were greater than the control population in 77% of the cases; 57% of kidney weights were more than one standard deviation above control values. Adjusted group mean kidney weights were 29.8 g (+/- 1.0 SE) in CDH cases and 25.9 g (+/- 1.5 SE) in the control population (P less than .04). These data support our hypothesis and demonstrate that in newborns with CDH and morphologically normal kidneys, there is significant renal enlargement associated with CDH. The presumed mechanism of this renal enlargement, as well as its relationship to normal and aberrant pulmonary growth and regulation are discussed. If such a selective PGF exists, its therapeutic implications for fetuses and newborns with PH are considerable. PMID- 2191108 TI - Incidence of neuroblastoma in Sapporo city. AB - The incidence of neuroblastoma in Sapporo City for the period before the enforcement of the mass screening of neuroblastoma (1974 to 1980) was compared with the period after it (1981 to 1987). No large difference was found in incidence between them. In 1981 to 1987 the occurrence cluster at 2 to 4 years of age found in the prescreening period disappeared and an accumulation of patients at 0 year of age was noted. The sensitivity of the mass screening was almost stable (76.9% to 80.0%) throughout the 7 years. By the mass screening system of Sapporo City, early detection will be expected in 60% to 70% of all the neuroblastoma patients, the deficiency of which is due to the patients who neglected the mass screening. PMID- 2191109 TI - Accessory limb associated with spina bifida. PMID- 2191110 TI - Identification of Actinobacillus actinomycetemcomitans by gold immunolabeling and scanning electron microscopy. AB - Recent evidence suggests that dental plaque is not a homogeneous bacterial mass but, on the contrary, specific bacterial morphotypes and species may be preferentially located within certain microenvironments. The aim of the present study was to develop combined gold immunolabeling and scanning electron microscopic (SEM) techniques for the identification of periodontal pathogens in subgingival dental plaque and on the root surfaces of extracted teeth. Suspensions of pure A. actinomycetemcomitans cultures or suspensions of A. actinomycetemcomitans mixed together with other oral bacteria were prepared, labeled with goat anti-rabbit IgG conjugated with 5 nm or 40 nm colloidal gold particles, and observed by SEM using both secondary and back-scattered imaging. Scanning electron microscopy demonstrated that the A. actinomycetemcomitans bacterial cell surface was specifically labelled. There was no cross-reaction with any of the other bacterial morphotypes. Only the labeled A. actinomycetemcomitans were visible in mixtures examined by back-scattered imaging scanning electron microscopy. The combined techniques of gold immunolabeling and SEM may, therefore, be useful in identifying A. actinomycetemcomitans in subgingival plaque samples and on the root surfaces of extracted teeth as well as in studies of bacterial ecology in dental plaque, in general. PMID- 2191111 TI - The effect of systemic metronidazole after non-surgical treatment in moderate and advanced periodontitis in young adults. AB - The effect of adjunctive systemic metronidazole was studied in patients with moderate and advanced periodontitis recalcitrant to comprehensive non-surgical treatment. The material originated from a randomly selected part of the population aged 31 to 40 years. After non-surgical treatment of 149 patients, 98 with persisting pathological pockets greater than or equal to 5 mm (52 men and 46 women) became the subjects for the study. Clinical parameters were registered and pocket contents subjected to laboratory analysis. The subjects were randomized into two groups according to a code list known only by the manufacturer and the statistician. The test group took three 400 mg metronidazole tablets daily for 1 week and the control group took placebo tablets. Reassessment 6 months later showed statistically significant clinical improvement, with a reduction in the number of sites greater than or equal to 5 mm in both test and control groups. Complete healing, with no pockets greater than or equal to 5 mm, was noted in 30% of the test group and 9% of the control group. The difference is statistically significant and shows the supplementary effect of adjunctive metronidazole in non surgical treatment of moderate and advanced periodontitis. PMID- 2191112 TI - Antibody to collagen type I in gingival crevicular fluid. AB - Gingival crevice fluid (GCF) was collected from inflamed sites in 20 patients before and 6 weeks after treatment. Levels of IgG to human collagen Type I were measured in the GCF and autologous serum using an enzyme-linked immunosorbent assay and compared with levels in control sera. IgG antibody to collagen was detected in GCF at significantly (P less than 0.01) higher levels than in control sera, but these levels were not significantly (P greater than 0.05) different from those in autologous sera. The levels of IgG antibody in GCF and autologous sera did not alter significantly (P greater than 0.05) after treatment. IgG antibody to collagen Type I is present in GCF in the diseased and healing state. PMID- 2191113 TI - Quality of life in a placebo-controlled trial of zidovudine in patients with AIDS and AIDS-related complex. AB - We measured quality of life using the Karnofsky Performance Status and Quality of Well-Being scale (QWB) for 31 patients with AIDS and AIDS-related complex in a placebo-controlled trial of zidovudine. Sixteen patients were randomized to zidovudine and 15 to placebo. We recorded nine scores for each patient during 1 year. During the blinded trial, 3 patients receiving placebo died; at 1 year, one had died in the zidovudine group and 10 in the placebo group. Repeated-measures analysis of variance demonstrated that mean scores declined less for the zidovudine group than for the placebo group during the blinded trial (p less than 0.03) and during 1 year (p less than 0.002). However, because the QWB incorporates death into its score, these results largely reflected differences in mortality. When data from those who died were excluded, Karnofsky scores were higher for the zidovudine group at the end of the blinded trial (p less than 0.02), but at 1 year no significant differences were observed between groups. The QWB and other quality-of-life measures may contribute to more comprehensive evaluation of AIDS treatments, and may detect treatment effects earlier. Whether existing measures can detect real differences among survivors will require testing in patients with less advanced disease. PMID- 2191114 TI - [Bicarbonate secretion in the mucosal defensive mechanism of the duodenum. Acid neutralization with HCO3- in the lumen and mucus gel]. AB - Bicarbonate secretion from the surface epithelial cells in the duodenum is an active process depending on tissue metabolism and blood flow, and regulated by humoral and neuronal factors as well as endogenous prostaglandins (PGs). The duodenal mucosa has been also able to respond luminal acid by a significant rise in alkaline secretion, mediated mainly by PGs, and the impairment of this process is involved in the pathogenic mechanism of various duodenal ulcer models. The mechanism of mucosal protection by HCO3- secretion is two ways: one is neutralization of luminal acid, and the other the establishment of pH gradient in the mucus gel with the aid of the physicochemical property of mucus. Although the majority of H+ is neutralized by secreted HCO3- in the lumen and mucus gel, the ultimate mucosal protection is ensured by removal of back-diffused H+ through intramucosal neutralization with HCO3- and translocation by blood flow. Thus, HCO3- secretion in collaboration with mucus plays an important role as the first line of defense (pre-epithelial barrier) in the duodenal mucosal protection. PMID- 2191117 TI - The theories of Thomas Sydenham (1624-1689). PMID- 2191116 TI - The origins of the Common Cold Unit. AB - In 1941 Harvard University and the American Red Cross provided an epidemiological team and an infectious diseases hospital for Britain. Since 1946 the buildings have been occupied by the Common Cold Unit where research has been carried out into many aspects of the causative viruses and their role in the disease, and also into methods of preventing it. The establishment is to be closed down this year. PMID- 2191115 TI - Mechanisms of bacterial degradation and transformation of chlorinated monoaromatic compounds. AB - Chloroaromatics are xenobiotic compounds of environmental concern. They can be removed from the environment by (bio)degradation or by (bio)transformation. Recognition of the mechanisms and requirements of their biodegradation is of cardinal importance for understanding the fate of these chemicals in the environment, and for developing methods for biological treatment of wastes containing compounds of this type. Cleavage of the carbon-halogen bond is the critical step in degradation of chloroaromatics. As exemplified with chlorophenols, chlorobenzoates and chlorobenzenes in this review, two distinct strategies are employed by bacteria for degradation of chlorinated aromatic compounds: the particular chlorine substituents are removed either directly from the aromatic ring (as an initial step in degradation) or after oxygenative ring cleavage (from chlorinated aliphatic intermediates). Direct elimination of chlorine substituents from the aromatic ring occurs by displacement with either hydroxyl groups (hydrolytically or oxygenolytically) or hydrogen atoms (reductive dechlorination). Dechlorinations of the latter type require reducing power and are significant in anaerobic environments, but have also been observed with strictly aerobic bacteria. Various biotransformation reactions, with only minor alteration of the parent compound, are an alternative to biogradation. Two environmentally significant transformation reactions discussed here are O methylation and O-demethylation. The capability to O-methylate chlorinated hydroxybenzenes seems to be widespread in bacteria. O-Methylation is an environmentally important transformation reaction, since methylation increases the lipophilicity of the compound and thus the potential for bioaccumulation. Bacterial O-demethylation of chlorinated methoxylated compounds has been observed under both aerobic and anaerobic conditions. PMID- 2191118 TI - [Current patterns of the use of heparin in angiography]. AB - All members and fellows of the Society of Cardiovascular and Interventional Radiology were surveyed to determine current patterns of heparin use in angiography. Five hundred responses (68%) were received. In general, significant differences exist across the United States in the mean heparin dose for angiography, mean dose for angioplasty, heparin concentration in flush solutions, and, especially, frequency with which heparin is mixed with nonionic contrast media. Few respondents routinely use systemic (bolus) heparinization for angiography. Heparin concentration in flush solutions varies from 0 IU/L to 12,000 IU/L. Eleven percent of respondents mix heparin with nonionic contrast agents, at a median dose of 5 IU/mL. Results of this survey reveal patterns of practice but do not represent a standard of practice. Protocols for heparin use should be based on experimental evidence, and heparin dosage must be individualized for each procedure and each patient. Large-scale, prospective studies of the merits of systemic heparinization and of mixing heparin with nonionic contrast agents are needed. PMID- 2191119 TI - [Rare tumors of the exocrine pancreas]. PMID- 2191120 TI - [Congenital luxation of the hip. Its detection: when? How? For whom?]. PMID- 2191121 TI - [Imaging of malignant lymphoma of muscular sites]. AB - Seventeen cases of muscular lymphoma are reported (5 primary non-Hodgkin lymphoma, 11 secondary NHL, 1 secondary Hodgkin's disease). The psoas or gluteus muscle was involved in 10 cases, and the lower limb was affected in the remaining 7 cases. Nine cases of muscular extension of bone NHL are also reported. On sonograms these lesions were always large and less echogenic than adjacent structures, with no signs of necrosis before treatment. US and CT patterns were comparable for both primary and secondary lesions, regardless of the type of lymphoma or whether or not there was any previous bone lesion. Associated lymphomatous lesions were observed in 14 cases. On angiograms, muscular lymphomatous involvement presented a hypovascular pattern. While ultrasonography is an excellent monitoring technique for soft tissue lymphomas (specially for the lower limbs), a major contribution of CT is the detection and the follow-up of deep or thoracic wall lesions. PMID- 2191122 TI - [Gastric duplication. Apropos of 3 cases]. AB - Duplication of the stomach is a rare congenital malformation. Most reported cases involve infants or young children. On the basis of 3 cases identified at a later age, we describe the CT appearance of this malformation. Those 3 cases were demonstrated by the histological study of the surgical specimen. PMID- 2191124 TI - [Consensus conference on the detection of localized cancer of the prostate]. PMID- 2191123 TI - [Feasibility study of the Doppler exploration of the renal artery]. AB - Using arteriography as a reference, the authors investigate the feasibility of pulsed doppler exploration of the normal or pathological renal arteries in 46 successive patients. The poor sensitivity of pulsed doppler, mainly due to the considerable anatomical variations of the renal pedicle, does not currently allow using this technique for the detection of renal arterial stenosis. When combined with angiography, pulsed doppler becomes a definite asset in therapeutic radiology to help in the choice of a treatment and in follow-up. PMID- 2191126 TI - Fetal malformations commonly detectable on obstetric ultrasound. AB - A review of 364 fetuses with a total of 570 malformations discovered on ultrasound throughout the Emanuel Hospital referral pattern from 1978 to 1987 was compared to a previous multicenter study of 50,282 children from 1959 to 1965 that found minor or major congenital malformations in 6.5% of children, for a rate of 8.8 malformations per 100 children. The comparison was made to determine which of the malformations reported in the earlier study were commonly detectable on obstetric ultrasound as performed throughout the referral area and to determine what the combined prevalence of those malformations was within the general population. For the comparison, the number of patients undergoing obstetric ultrasound throughout our referral area was estimated from the number of anencephalic fetuses found. The relative prevalences of all malformations in the two groups were then determined by extrapolation. The malformations commonly detectable on ultrasound according to that comparison were then assigned the prevalences obtained from the earlier clinical study. According to this analysis, 0.7-0.8% of fetuses have major malformations commonly detectable on ultrasound, for a rate of 1.2 malformations per 100 fetuses. That represents about 13% of all malformations and about 27% of major malformations. If cardiovascular abnormalities, cleft lip and clubfoot were usually detected, the rate of malformations considered commonly detectable would increase to 2.7 per 100 fetuses. That would represent about 31% of all malformations and about 63% of major ones. PMID- 2191125 TI - Treatment of Chlamydia trachomatis identified with Chlamydiazyme during pregnancy. Impact on perinatal complications and infants. AB - A rapid enzyme immunoassay antigen detection system (Chlamydiazyme) was used to screen 199 asymptomatic, third-trimester women. Fifty-two (26%) were Chlamydiazyme positive; they were mostly primiparous, single, young and black. Infected women were offered erythromycin therapy, counseling and posttherapy retesting. Sexual partners were treated likewise. Erythromycin compliance, determined by a questionnaire, was high (92%), and side effects (16%) were tolerable. Pregnancy outcome and infant illnesses were monitored to determine the effectiveness of therapy. There were no significant differences in pregnancy outcome in the Chlamydiazyme-negative and treated, Chlamydiazyme-positive women. Prospective evaluation of infants born to 48 negative and 50 treated, Chlamydiazyme-positive women revealed no significant differences in the incidence of respiratory tract illnesses or conjunctivitis. Chlamydiazyme can be used in a screening program to identify and treat third-trimester women infected with C trachomatis. As previously reported, erythromycin therapy for colonized women interrupted the expected transmission of C trachomatis to their infants. PMID- 2191127 TI - Correlation of absorbance at 650 nm with the presence of phosphatidylglycerol in amniotic fluid. AB - Amniotic fluid absorbance at 650 nm was correlated with the presence of phosphatidylglycerol (PG) in the isolated surfactant fraction (10,000-g pellet). Shake test results were included. Two hundred ninety-seven samples were analyzed. PG was present in 222 of 226 samples in which the absorbance was greater than or equal to 0.250 and absent from 48 of 71 with an absorbance less than 0.250. PG was present in all 166 samples with a positive shake test and absent in 52 of 131 samples with a negative one. In 65 samples in which the shake test was negative and the absorbance greater than or equal to 0.250, PG was present in all but 4. The false-positive rate for the prediction of respiratory distress syndrome was 0.8% for the Shake test and 0.6% for the absorbance measurement. The results support the usefulness of the absorbance measurement as a simple and reliable procedure for assessing fetal lung maturity. PMID- 2191128 TI - Ruptured tuboovarian abscess in early gestation. A case report. AB - A woman with a ruptured tuboovarian abscess was treated surgically at nine weeks' gestation. She subsequently had an uneventful pregnancy and delivery. PMID- 2191129 TI - Gunshot wounds to the gravid uterus. A case report. AB - A pregnant woman sustained an abdominal gunshot wound during the second trimester; the bullet injured multiple loops of bowel and passed through the uterus, placenta and fetus. Although the stillborn fetus was delivered by cesarean section, a review of the literature indicated that operative delivery is not indicated when the fetus has died already. Labor and delivery are well tolerated, and an unnecessary hysterotomy is thus avoided. If labor does not ensue spontaneously, it can be induced. Approximately 40% of fetuses will survive the initial injury. In past reviews the risk of prematurity often outweighed the benefits of delivery of those infants. Advances in neonatology now make survival routine after 28 weeks' gestation, and viable fetuses should be delivered promptly by cesarean section to decrease the risk of delayed death from fetal or placental injury. PMID- 2191130 TI - Ultrasonic study of amnioinfusion. A report of two cases. AB - Two patients had amnioinfusion with subsequent improvement in fetal heart rate (FHR) patterns. Ultrasound in case 1 showed a pocket of saline around the umbilical cord and improved FHR. Case 2 likewise had an improvement in the FHR without ultrasonic evidence of a protective pocket of fluid. Case 2 actually had a tight true knot in the cord, which explained the abnormal FHR pattern. Amnioinfusion can form a protective pocket of fluid around the umbilical cord in cases of severe oligohydramnios, although in our experience its success rate is low and unpredictable. PMID- 2191131 TI - Sonographic accuracy in the diagnosis of ovarian masses. AB - Prediction of the tissue diagnosis of ovarian masses has remained a challenge for the sonographer since many adnexal masses have nonspecific sonographic appearances. We evaluated the accuracy of the sonographic diagnosis of adnexal masses in 100 women undergoing laparotomy for ovarian masses within eight weeks of an ultrasound study. Comparison of the preoperative sonographic and final pathologic diagnoses revealed a correct sonographic diagnosis in 68% of the cases. In addition, sonography correctly identified a benign condition in 17% of the cases, though without arriving at the exact tissue diagnosis. Sonography was frankly misleading in 15% of the cases, misreading whether the lesions were benign or malignant. The identification of ovarian malignancy was correct in 24/30 patients (sensitivity, 80%), and the specificity for correctly diagnosing a benign condition was 87%. The positive predictive value of a sonographic diagnosis of an adnexal malignancy was 73%. The negative predictive value of sonography for excluding a malignancy was 91%. PMID- 2191132 TI - Plasma glucose and insulin levels during the menstrual cycles of normal women and premenstrual syndrome patients. AB - Three-hour oral glucose tolerance tests were performed on days 5 and 25 of ovulatory menstrual cycles in 26 women. The women were divided into normal (n = 9) and premenstrual syndrome (PMS) (n = 17) categories. Ovulation was confirmed by basal body temperature records and plasma progesterone levels. There were no statistically significant changes in the plasma glucose or insulin levels between the two tests in either group. Except for a higher two-hour plasma insulin concentration on the day 5 test in normal women, no statistically significant carbohydrate differences were noted between the groups. The data suggest that alterations in carbohydrate metabolism are not important in PMS. PMID- 2191133 TI - Effect of indomethacin on the fetal ductus arteriosus during treatment of symptomatic polyhydramnios. AB - Ten pregnancies with 13 fetuses complicated by symptomatic polyhydramnios were treated with indomethacin. A baseline fetal echocardiogram was obtained before therapy, repeated 24 hours after the initiation of indomethacin and then performed weekly provided that the ductus arteriosus remained patent. The mean duration of indomethacin therapy was 28.3 +/- 18.9 days. The starting dose in all patients was 25 mg orally every six hours. The ductus arteriosus was noted to constrict in four patients, with the development of tricuspid regurgitation in one. One of the constrictions occurred after 23 days of therapy. In one patient with constriction a reduction of the indomethacin dosage was not associated with constriction, while in the other three, constriction was still evident at a reduced dosage. All constrictions and the tricuspid regurgitation resolved in utero within 24 hours after discontinuation of the indomethacin. We recommend careful monitoring of the fetal ductus arteriosus when treating symptomatic polyhydramnios with indomethacin. PMID- 2191134 TI - Group A beta-hemolytic Streptococcus as a cause of toxic shock syndrome. A case report. AB - Group A beta-hemolytic Streptococcus (pyogenes) has been associated recently with toxic-shock-like syndrome similar to staphylococcal toxic shock as described originally in 1978. A group A beta-hemolytic streptococcal infection occurred in a recent postpartum patient and clinically resembled staphylococcal toxic shock. PMID- 2191135 TI - Midgut volvulus in pregnancy. A case report. AB - Midgut volvulus in pregnancy is rare. Preoperative diagnosis is difficult and may be complicated by pregnancy, labor and the post-cesarean-section state. In a case of total midgut volvulus after cesarean section, a massive resection of the small bowel was performed. PMID- 2191136 TI - Analysis of Scottish Duchenne and Becker muscular dystrophy families with dystrophin cDNA probes. AB - One hundred and thirty-two Scottish families, representing the majority of currently known cases in this country with at least one living subject affected by DMD (110) or BMD (22), were studied with a series of cDNA probes excluding the 3' region of the gene (probes 10-14). Using mainly HindIII digested DNA from affected males, 89 patients showed deletions which ranged from 1 to 32 HindIII fragments in size. Two patients were also detected with exon duplications. Abnormalities were found to be particularly concentrated in the area of probe cDNA 8, with 56 patients being deleted for at least one of the fragments detected by this probe. A second smaller concentration of deletions was found with probe 1 2a which showed 16 deletions and two duplications. The endpoints of cDNA deletions or duplications were determined with a maximum variability of one HindIII fragment in 83 patients, while the remaining eight patients had a single deletion endpoint defined. The deletions found in two of our patients appear to conflict with the previously stated exon order at the 5' end of the gene. Although no specific deletion patterns were apparent for DMD, the deletions found in 13 of the BMD patients all included the most proximal (10 kb) fragment detected by probe 8. PMID- 2191137 TI - Computer control systems and pharmacological drug administration: a survey. PMID- 2191138 TI - Estimating the total number of lymphatic valves in infant lungs with the fractionator. AB - The fractionator is illustrated by means of a biomedical example involving the estimation of the number of lymphatic valves in lungs of infants who had died from sudden infant death syndrome (SIDS) and other known causes. The method is unbiased irrespective of tissue deformations and it does not require external information such as section thickness. An upper bound of the coefficient of error of the estimate of the number of valves within one lung was 6.5%, despite the fact that the number of valves counted per lung at the last stage ranged between 11 and 37 only. The upper bound includes the biological variation of the number of valves among infant lungs. Some theoretical remarks are also made on the efficiency of the fractionator. It is suggested, for instance, that the initial sampling stages cause more impact on the precision of the final estimator than the subsequent stages, and that an optimal arrangement of fragments submitted to systematic sampling should have the smallest fragments at the ends, with fragment contents increasing smoothly toward the middle of the series. PMID- 2191139 TI - Base-pairing interactions involving the 5' and 3'-terminal nucleotides of group II self-splicing introns. AB - By combining comparative sequence analyses and nucleotide replacements, we show that formation of the active center of group II introns rests in part on two novel long-range base-pairing interactions. (1) The last nucleotide of group II introns forms a solitary Watson-Crick base-pair with one of the nucleotides in the short sequence stretch connecting domains II and III. Formation of this base pair is rate-limiting for the 3' cleavage and ligation step. (2) Nucleotides 3 and 4 form base-pairs with two consecutive nucleotides in a well-conserved internal loop of domain I. This interaction is involved in both the 5' and 3' cleavage steps. Possible relationships between group II and nuclear pre-mRNA introns are reassessed by taking into account these new pieces of information. PMID- 2191140 TI - Translated translational operator in Escherichia coli. Auto-regulation in the infC-rpmI-rplT operon. AB - The genes coding for translation initiation factor IF3 (infC) and for the ribosomal proteins L35 (rpmI) and L20 (rplT) are transcribed in that order from a promoter in front of infC. The last two cistrons of the operon (rpmI and rplT) can be transcribed from a weak secondary promoter situated within the first cistron (infC). Previous experiments have shown that the expression of infC, the first cistron of the operon, is negatively autoregulated at the translational level and that the abnormal AUU initiation codon of infC is responsible for the control. We show that the expression of the last cistron (rplT) is also autoregulated at the posttranscriptional level. The L20 concentration regulates the level of rplT expression by acting in trans at a site located within the first cistron (infC) and thus different from that at which IF3 is known to act. This regulatory site, several hundred nucleotides upstream from the target gene (rplT), was identified through deletions, insertions and a point mutation. Thus, the expression of the operon is controlled in trans by the products of two different cistrons acting at two different sites. The localization within an open reading frame (infC) of a regulatory site acting in cis on the translation of a downstream gene (rplT) is new and was unforeseen since ribosomes translating through the regulatory site might be expected to impair either the binding of L20 or the mRNA secondary structure change caused by the binding. The possible competition between translation of the regions acting in cis and the regulation of the expression of the target gene is discussed. PMID- 2191141 TI - A site in the T4 bacteriophage major head protein gene that can promote the inhibition of all translation in Escherichia coli. AB - The cryptic DNA element, e14, synthesizes a protein, Lit, which can inhibit gene expression late in T4 bacteriophage development. This inhibition is due to the interaction between the Lit protein and a short region, the gol region, within gene 23, the major head protein gene of phage T4. We have constructed plasmids in which the gol region is transcribed from the lac promoter and fused translationally and transcriptionally to lacZ and cat (chloramphenicol acetyltransferase). These fusion plasmids were used to demonstrate that, in the presence of Lit protein, the gol region inhibits the expression of genes downstream in the same transcription unit. This local inhibition does not require the gene 23 polypeptide from the gol region. In addition, inducing the transcription and translation of the gol region in the presence of Lit protein causes an immediate global inhibition of all translation in Escherichia coli. This global inhibition does require the gene 23 polypeptide. No more than 75 base pairs of DNA from the gol region are required for both the local and global inhibitions. The gol region sequence contains a short dyad symmetry. However, it is the sequence of bases in the region of dyad symmetry and not the ability to form a hairpin in the RNA that is required for gol region activity. PMID- 2191143 TI - Antibiotic prophylaxis diminishes bacterial translocation but not mortality in experimental burn wound sepsis. AB - Pseudomonas (PSA) burn wound sepsis results in prolonged bacterial translocation (BT) of enteric organisms such as E. coli to the mesenteric lymph nodes (MLN) and organs in rats. Intestinal decontamination with oral antibiotics may improve mortality after burn injury, perhaps due to decreased BT. To determine the effect of oral antibiotic prophylaxis effective against E. coli but not PSA on BT and subsequent mortality in a model of PSA burn wound sepsis, rats were given a 30% scald burn and wound inoculation with 10(8) PSA followed by randomization to either ampicillin (50 mg/kg/d) or saline gavage. Cultures of MLN, organs, blood, and cecal contents were obtained on days 1, 4, and 7 after injury, with additional animals observed for 14-day mortality. Although oral antibiotic prophylaxis resulted in increased cecal colony counts, the incidence of BT was unchanged. The number of organisms present in both the MLN and organs, however, was significantly reduced with prophylaxis, indicating cecal overgrowth by non translocating bacteria. Reduction of the number of translocating organisms did not result in improved mean survival time after injury, suggesting that mortality from PSA burn wound sepsis occurs independently of bacterial translocation. PMID- 2191142 TI - Temporary abdominal closure (TAC) for planned relaparotomy (etappenlavage) in trauma. AB - Planned relaparotomy (temporary abdominal closure) was studied prospectively in 20 trauma patients. Four died in the first 24 hours from hypothermia, coagulopathy, shock (three), and septic shock (one). The 16 survivors had a Velcro-like prosthetic placed to facilitate abdominal closure and re-entry. Prosthetic was necessary in eight because bowel edema precluded fascial closure, and useful for removal of packing (three) and for the management of peritonitis (five). The prosthetic did not open spontaneously, nor was it associated with evisceration or bowel fistula. Temporary abdominal closure (TAC) permitted reappraisal and staged repair of intra-abdominal pathology, including bowel resection and anastomosis. TAC identified 14 problems early: bleeding (five), bile leaks (two), GI complications (six), liver necrosis (one). Five patients developed superficial wound infections, and three went on to develop fascial necrosis. PMID- 2191144 TI - Interposition of the thymus as a pedicled flap in tracheal reconstructive surgery. AB - Thymus was interposed in six patients following tracheal reconstruction: three tracheo-innominate fistula repairs, two resections for stenosis, and one repair of a membranous tear during esophagectomy. The two resections for stenosis were elective; the others were emergent repairs. This gland, readily accessible in the upper mediastinum, is easily dissected from the pleura and pericardium and separated into two lobes. Pedicles based at the thoracic inlet measure between 15 and 20 cm by 4 cm. Each lobe receives independent arterial blood supply and venous drainage which remains intact even if the innominate vein must be divided to effect tracheal repair. All patients survived the perioperative period. The patient with the tracheo-innominate fistula died 1 month later. No patient had evidence of further vascular complications or tracheal anastomotic leak even though one patient developed a long segment of necrotic trachea. Reinforcement following tracheal reconstruction is important in preventing complications from anastomotic leak or vascular erosion. The pedicled thymus gland is an excellent, readily available interposition flap for emergent or elective tracheal reconstruction. PMID- 2191145 TI - Abdominal CT in the evaluation of patients with stab wounds of the back. PMID- 2191146 TI - Prospects for standardized assays in vector biology. AB - The benefits of technological advances continue to accrue at an ever accelerating rate. In 1987 I presented a brief review of recent advances and applications of biotechnology to the study of arthropods and disease-vector relationships. Since 1987 progress has been made in practically all areas included in that earlier review and I want to give brief mention of just a few significant advances that have appeared in print since that time. An obvious spin-off of modern technology has been the production of continually improved tools to aid in species identification. This is true for the arthropods as well as for pathogenic organisms transmitted by arthropods. Consequently, we can now approach the problems presented by species complexes with an array of techniques, and we find that we are limited only by our access to the necessary reagents, grasp of the technology and funding. Likewise, in studies of arthropod-pathogen relationships, many new tools have been developed for detection of pathogens in the vectors and these tools are applicable to field and laboratory investigations into the many issues of vector competence. PMID- 2191147 TI - Noninfectious human immunodeficiency virus type 1 mutants deficient in genomic RNA. AB - All retroviruses contain, in the nucleocapsid domain of the Gag protein, one or two copies of the sequence Cys-X2-Cys-X4-His-X4-Cys. We have generated a series of mutants in the two copies of this motif present in human immunodeficiency virus type 1. These mutants encoded virus particles that were apparently composed of the normal complement of viral proteins but contained only 2 to 20% of the normal level of genomic RNA. No infectivity could be detected in the mutant particles, while 10(5) infectious U were present in an equivalent amount of wild type particles. Thus, the mutants have another defect in addition to the inefficiency with which they encapsidate genomic RNA. Our results show that both copies of the motif are required for normal RNA packaging and for infectivity. Mutants of this type may have important applications, including nonhazardous materials for research, immunogens in vaccine and immunotherapy studies, and diagnostic reagents. PMID- 2191148 TI - Generation of seal influenza virus variants pathogenic for chickens, because of hemagglutinin cleavage site changes. AB - Influenza virus A/seal/Mass/1/80 (H7N7) was adapted to grow in MDCK cells and chicken embryo cells (CEC) in the absence of exogenous protease. The biological properties of the virus variants obtained coincided with intracellular activation of the hemagglutinin (HA) by posttranslational proteolytic cleavage and depended on the cell type used for adaptation. MDCK cell-adapted variants contained point mutations in regions of the HA more distant from the cleavage site. It is proposed that these mutations are probably responsible, through an unknown mechanism, for enhanced cleavability of HA in MDCK cells. Such virus variants were apathogenic in chickens. CEC-adapted variants, on the other hand, contained an insertion of basic amino acids at the HA cleavage site, in addition to scattered point mutations. The insertions converted the cleavage sites in the variant virus HAs so that they came to resemble the cleavage site found in highly pathogenic avian influenza viruses. CEC variants with such cleavage site modifications were highly pathogenic for chickens. The lethal outcome of the infection in chickens demonstrated for the first time that an influenza virus derived from a mammalian species can be modified during adaptation to a new cell type to such an extent that the resulting virus variant becomes pathogenic for an avian species. PMID- 2191149 TI - Hepatitis B virus nucleocapsid assembly: primary structure requirements in the core protein. AB - As a step toward understanding the assembly of the hepatitis B virus (HBV) nucleocapsid at a molecular level, we sought to define the primary sequence requirements for assembly of the HBV core protein. This protein can self assemble upon expression in Escherichia coli. Applying this system to a series of C terminally truncated core protein variants, we mapped the C-terminal limit for assembly to the region between amino acid residues 139 and 144. The size of this domain agrees well with the minimum length of RNA virus capsid proteins that fold into an eight-stranded beta-barrel structure. The entire Arg-rich C-terminal domain of the HBV core protein is not necessary for assembly. However, the nucleic acid content of particles formed by assembly-competent core protein variants correlates with the presence or absence of this region, as does particle stability. The nucleic acid found in the particles is RNA, between about 100 to some 3,000 nucleotides in length. In particles formed by the full-length protein, the core protein mRNA appears to be enriched over other, cellular RNAs. These data indicate that protein-protein interactions provided by the core protein domain from the N terminus to the region around amino acid 144 are the major factor in HBV capsid assembly, which proceeds without the need for substantial amounts of nucleic acid. The presence of the basic C terminus, however, greatly enhances encapsidation of nucleic acid and appears to make an important contribution to capsid stability via protein-nucleic acid interactions. The observation of low but detectable levels of nucleic acid in particles formed by core protein variants lacking the Arg-rich C terminus suggests the presence of a second nucleic acid-binding motif in the first 144 amino acids of the core protein. Based on these findings, the potential importance of the C-terminal core protein region during assembly in vivo into authentic, replication-competent nucleocapsids is discussed. PMID- 2191150 TI - Structure and expression of tat-, rev-, and nef-specific transcripts of human immunodeficiency virus type 1 in infected lymphocytes and macrophages. AB - Primary RNA transcripts from the human immunodeficiency virus type 1 (HIV-1) are processed into mature mRNA by a complex series of splicing events. Viral structural proteins and reverse transcriptase are translated from unspliced or singly spliced transcripts. Proteins which control virus replication, including tat, rev, and nef, are translated from transcripts which are the product of multiple splicing. We have analyzed the composition and relative abundance of the latter transcripts in long-term infected cell lines and in acutely infected peripheral blood cells by amplification with the polymerase chain reaction (PCR) followed by Southern blot, molecular cloning, and DNA sequence analyses. In H9 cells chronically infected with the HIV-1 strain HTLV-IIIB, the predominant of the three kinds of transcripts is those coding for nef. Transcripts with coding potential for rev constituted an intermediate fraction of those analyzed, while those for tat accounted for only a small minority. A similar pattern was observed with Southern blots of PCR-amplified transcripts from peripheral blood lymphocytes acutely infected with HTLV-IIIB. The same general pattern was also observed with PCR-amplified transcripts from peripheral blood monocyte macrophages infected with an HIV-1 strain (BA-L) able to grow to high titers in macrophages. In these cells, however, the apparent major form of nef transcript contained only the first and third exons of the multiply spliced transcripts and appeared to be generated by either a single or a triple splicing mechanism. As with lymphocytes, tat-specific mRNAs were by far the least abundant. It thus appears that different cell types infected with different strains of HIV-1 maintain a similar balance of expression in which transcripts for nef vastly predominate over those for tat and that those for rev are intermediate in abundance. PMID- 2191151 TI - Expression and biochemical characterization of human immunodeficiency virus type 1 nef gene product. AB - nef genes from human immunodeficiency virus type 1 isolates BH10 and LAV1 (lymphadenopathy-associated virus type 1) were expressed in Escherichia coli under the deo operon promoter. The two proteins found in the soluble compartment of the bacterial lysate were purified by ion-exchange column chromatography to apparent homogeneity. Determination of the amino-terminal sequence revealed glycine as the first amino acid in the Nef protein, indicating removal of the initiator methionine during expression in E. coli. Under native conditions, the recombinant Nef protein is a monomer of 23 kilodaltons. In denaturing polyacrylamide gels, however, BH10 and LAV1 Nef proteins migrate as 28 and 26 kilodaltons, respectively. GTP binding and GTPase activity were monitored during Nef protein purification. These activities did not copurify with the recombinant Nef protein from either the BH10 or the LAV1 isolate. Purified recombinant BH10 Nef protein was used as an immunogen to elicit mouse monoclonal antibodies. A series of monoclonal antibodies were obtained which reacted with sequences at either the amino or carboxy terminus of Nef. In addition, a conformational epitope reacting with native BH10, but not LAV1, Nef was isolated. PMID- 2191152 TI - Envelope cross-reactivity between human immunodeficiency virus types 1 and 2 detected by different serological methods: correlation between cross neutralization and reactivity against the main neutralizing site. AB - A total of 70 human immunodeficiency virus type 1 (HIV-1) and 42 HIV-2 antibody positive serum samples, collected from groups of individuals in which only one type of HIV prevails, were tested for cross-reactivity against HIV-2 and HIV-1 proteins by Western blot (WB) (immunoblot), radioimmunoprecipitation assay (RIPA), neutralization analysis, and enzyme-linked immunosorbent assay with as antigen synthetic peptides representing selected parts of the envelope (env) glycoproteins. Cross-reactions against the env glycoproteins were observed by WB in 10% (7 of 70) and by RIPA in 40% (28 of 70) of the HIV-1 antibody-positive serum samples and by WB in 29% (12 of 42) and by RIPA in 48% (20 of 42) of the HIV-2 antibody-positive serum samples. Testing by enzyme-linked immunosorbent assay against a 36-amino-acid peptide (Cys-301-Cys-336) of the external glycoprotein of strain HTLV-IIIB of HIV-1 (HIV-1HTLV-IIIB) (known to represent a dominating, linear neutralizing site) showed type-specific reactions in 67% (38 of 57) of HIV-1 antibody-positive serum samples. Type-specific reactions against a homologous 35-amino-acid peptide of strain SBL-6669 of HIV-2 (HIV-2SBL-6669) were found in 75% (30 of 40) of HIV-2 antibody-positive serum samples, and these reactions were correlated to neutralization against HIV-2SBL-6669. Cross reactions against these peptides were seen in 23% (13 of 57) and 33% (13 of 40) of the HIV-1 and HIV-2 antibody-positive serum samples, respectively. These cross reactions were correlated to cross-neutralization against HIV-1HTLV-IIIB and HIV 2SBL-6669. Cross-neutralization against one heterotypic virus strain was demonstrated in 16% (9 of 57) of HIV-1 antibody-positive serum samples and in 22% (5 of 22) of HIV-2 antibody-positive serum samples, but no correlation was found between cross-neutralization and env cross-reactivity in WB or RIPA. PMID- 2191153 TI - Humoral immune response to the bovine immunodeficiency-like virus in experimentally and naturally infected cattle. AB - Calves inoculated with bovine immunodeficiency-like virus (BIV) produced virus specific antibodies that could be detected from 2 weeks to 2.5 years postinoculation by using both indirect fluorescent-antibody and Western immunoblot assays. Antibodies were primarily to p26. Virus and BIV-specific antibodies were isolated from calves given BIV-infected blood. Antibodies to BIV proteins were found in sera from naturally infected cattle. PMID- 2191154 TI - Intravenous glycerol infusions: effect on free fatty acid metabolism. AB - The plasma-free fatty acid response to intravenous glycerol infused at 250 and 500 mumol/min was determined in five normal volunteers in the postabsorptive state. There was a drop in free fatty acid concentration in all five subjects (one-way ANOVA, p less than 0.01) after the glycerol infusion with no change in insulin concentration compared to the post-absorptive state. These results suggest that intravenous glycerol infusions decrease free fatty acid concentrations in the post-absorptive state by an insulin-independent mechanism. When pharmacologic nonisotopic glycerol infusions are used to determined lipolytic rate, simultaneous measurement of free fatty acid concentrations should be interpreted with caution. PMID- 2191156 TI - [The hundredth anniversary of the Japanese Journal of Dermatology]. PMID- 2191155 TI - The effect of high lipid diet on in vitro prostaglandin E2 and thromboxane B2 production by splenic macrophages. AB - Feeding animals a diet high in linoleic acid for 7 days had no effect on the in vitro production of PGE2 by unstimulated macrophages. Feeding animals the high linoleic acid diet for 30 days greatly increased the production of PGE2 by macrophages when they were unstimulated, but decreased the production of PGE2 when they were stimulated with LPS. Feeding animals a diet high in linoleic acid for 30 days increased the production of TxB2 by macrophages when they were unstimulated, but decreased the production of TxB2 when they were stimulated. Normal, unstimulated splenic macrophages produced almost 80 times more TxB2 than PGE2. However, when the macrophages were stimulated the ratio decreased to six or less because of a greater increase in PGE2 production. The high linoleic acid diet did not inhibit the antibody dependent cellular cytotoxicity of macrophages. PMID- 2191157 TI - [Expression of HLA-class II antigens in malignant melanoma]. AB - Sixteen primary and ten metastatic melanoma lesions were stained in indirect immunoperoxidase with HLA-DR, DP and DQ monoclonal antibodies. In primary lesions, HLA-DR, DQ and DP antigens were much more expressed in nodular melanoma lesions than in acral lentiginous melanoma lesions. In metastatic lesions HLA-DR, DQ and DP antigens were expressed more than in primary lesions, but there were no significant differences between ALM and NM. In primary melanoma, 82%, 75%, and 75% of lesions tested were stained by anti HLA-DR, DP and DQ monoclonal antibodies, respectively. In metastatic melanoma, 90% of the lesions tested were stained by anti HLA-DR, DP and DQ monoclonal antibodies. HLA-class II antigens on melanoma cells were much more expressed in cases of high levels of invasion, high degrees of lymphocyte infiltration, and lower melanin content. PMID- 2191158 TI - [Treatment of four cases of B-cell lymphoma]. AB - Four cases of B cell lymphoma, seen at the Department of Dermatology, Miyazaki Medical College, for the previous approximately 10 years, were reviewed. Case 1 was characterized by a localized tumours lesion on the head; the histologic picture was of the follicular, medium sized cell type. Complete remission for 8 years has been obtained after electron beam therapy and surgical removal of the tumor. Cases 2 and 3 had a histologic picture of diffuse, large cell type and were assumed to have a bad prognosis with standard chemotherapy. In addition to conventional chemotherapy, they were placed on noncross-resistant alternating combination chemotherapy with medium dosages of MTX, VP-16, VDS, PCZ MXT, PEP and ACR, so as not to develop cross resistance. Case 2 has been in complete remission for 11 months and case 3 for 7 months. Case 4 was a nodal lymphoma with skin lesions. This patient was treated mainly by local radiation therapy, but later died with leukemic changes and renal failure. Cutaneous B cell lymphoma should be treated vigorously and carefully, since it has a poorer prognosis than that of lymphoma of lymph node origin. PMID- 2191159 TI - Reactive oxygen species generation by Kupffer cells and blood monocytes of mice infected with Plasmodium berghei and the chloroquine treatment. AB - Generation of reactive oxygen species (ROS) by blood monocytes and Kupffer cells of normal and Plasmodium berghei infected mice treated at different levels of parasitaemia with chloroquine, were studied. Cells isolated at lower level of parasitaemia (less than 2%) produced ROS within the range of normal animals, whereas ROS production by the cells isolated from the animals at higher level of parasitaemia (greater than 20%), was significantly higher even without stimulation with latex particles. The ROS generation capacity of both normal and infected animals was less after the chloroquine treatment. This inhibitory effect of chloroquine may be beneficial in protecting the host from the adverse effect of reactive oxygen species by controlling their overproduction. PMID- 2191160 TI - [Relationship between atherosclerosis and the aging process]. AB - On this paper, author reviews studies on the relationship between atherogenesis and aging. An increase in serum lipid peroxide level increased the number of circulating vascular endothelial cells. This indicates that the free radical is an injury factor for endothelial cells. In addition macrophages discharged the active oxygen upon stimulation and incorporated oxidized low density lipoprotein. These results suggested that macrophages play a main role in the initiation of atheroma formation. A very small dose of H2O2 induced platelet aggregation in vitro. Thrombin has chemotactic and chemokinetic activity for the smooth muscle cell as does fibrinogen, fibronectin and oxidized LDL. Conclusion. These results suggest close association through free radicals between the aging process and atherogenesis. PMID- 2191161 TI - [Sleep disturbance in the elderly]. AB - Sleep structure is qualitatively and quantitatively changed by aging. The elderly usually go to bed in early evening and wake up in early morning, and they also take several naps in the day time. The polyphasic sleep is one of the typical sleep patterns found in the elderly. Comparing the sleep of the elderly with that of young adults by the method of polysomnography, the characteristics of the sleep of the elderly are in the prolongation of sleep latency, shortening of total sleep time, increase of Stage W and Stage 1, decrease of Stage 3 and 4, and also decrease of Stage REM and the advance of REM phase. Insomnia is a frequently observed symptom in the elderly. The so-called psychophysiological insomnia due to transient psychological or situational stress is common in the elderly. However, insomnia following the mental disturbance (depression), chronic use of drug or alcohol, dementia (vascular or Alzheimer type) are also important in the elderly. Sleep apnea syndrome is recently found as an important cause of insomnia. Concerning the treatment and prevention of insomnia, it is necessary to exclude the causes of insomnia, to improve the environmental conditions and to keep the regular rhythm of sleep-wake cycle. It is also important to carefully select and use the adequate hypnotics considering the pharmacokinetics and adverse effects of the drugs in the elderly. PMID- 2191162 TI - [An aged woman with minimal change nephrotic syndrome complicated with reversible acute renal failure]. AB - Reported was an aged woman (80-year-old) of minimal change nephrotic syndrome which was complicated with reversible oliguric acute renal failure. The patient presented massive proteinuria, anasarca, and severe azotemia. She recovered conservatively from the acute renal failure and subsequently remitted from the nephrotic syndrome after the treatment which comprised albumin infusion, diuretics, adrenocorticosteroid hormones (including the pulse therapy), antiplatelet drug, and anticoagulants. The histopathologic findings of renal biopsy were compatible with minor glomerular abnormalities and acute tubular necrosis with many tubular casts. The previously reported cases older than 80 year-old which remitted from minimal change nephrotic syndrome complicated with reversible acute renal failure, were very rare. The present case was the second case among the literatures. PMID- 2191163 TI - [Distribution of N-isopropyl-p-[I-123]iodoamphetamine among the peripheral blood components: an in vitro study]. AB - With the purpose to clarify dynamics of N-isopropyl-p-[I-123]iodoamphetamine (I 123 IMP) in the blood stream its binding to the peripheral blood components was determined by in vitro experiment. I-123 IMP was added to the peripheral venous blood obtained from healthy volunteers to be incubated for different length of time (0-30 min) at 37 degrees C. The blood was then separated into blood cells and plasma. From the latter platelet rich plasma were separated. Radioactivity in each blood component was counted in a well type scintillation counter respectively. To evaluate the affinity of I-123 IMP to red blood cell the component containing blood cells were washed repeatedly with salines. It was found that the fraction of radioactivity in the blood cell component was 68.0 +/- 6.3% (m +/- 1 S.D.), which was higher than that in the plasma (32.0% +/- 6.3%). The radioactivity in the platelet-rich plasma was only 1.7 +/- 1.1% of the total I-123 IMP activity. This percentage did not change by the incubation time. When Tc-99m DTPA was incubated with blood, radioactivity in the blood cell component was only 22.5%, which is further lowered by 32 +/- 2.1% after each washing to reach 6.8% after three times washing. In contrast the radioactivity of I-123 IMP in blood cell component remained as high as 31.1% after eight times washing. Almost constant fraction (8.20 +/- 0.57%) of radioactivity was freed into supernate by each washing. These findings suggest that a certain specific binding mechanism is involved in the binding of I-123 IMP to red blood cells. PMID- 2191165 TI - Health access America. PMID- 2191166 TI - Goals and accomplishments of the AMA. PMID- 2191164 TI - [A case of thymolipoma on the cervicomediastinal area]. AB - Thymolipoma is a very rare mediastinal tumor. We reported a case of 52-year-old female with thymolipoma which was located in the cervicomediastinal area. The chest X-ray film revealed an abnormal shadow in the superior mediastinum. Computed Tomography (CT) clearly showed the existence of a large mass in the left side of the trachea. The angiogram showed that there was a stenosis on the left brachiocephalic vein. On June 13, 1988, median sternotomy was performed. A large tumor, about 5.5 x 13 x 5.5 cm, was found arising from the left cervical area. This tumor was excised completely and thymolipoma was diagnosed histopathologically. The post-operative course was very satisfactory. PMID- 2191167 TI - [The present aspect of tuberculous pleurisy--report of the 29th series (A) of CSUCT--Cooperative Study Unit of Chemotherapy of Tuberculosis (CSUCT) of the National Sanatoria in Japan]. AB - CSUCT carried out 9-21 month's follow up of 273 patients with exudative tuberculous pleurisy who were admitted to 39 national sanatoria in 1985, and were treated for the first time. The background factors of the patients at the time of admission were as follows: the average age, 47.2; male/female ratio 3:1; idiopathic pleurisy 163 cases and secondary pleurisy 110 cases. Distribution of maximal temperature on admission; 37.0 degrees C or less 24.4%; 37.1-38.0 degrees C 37.8%; 38.1-39.0 degrees C 28.5%; higher than 39.0 degrees C 9.3%. Younger patients tended to show higher temperature than the older. The positivity of tuberculin reaction was 84.3%, and among them 34% were strongly positive (greater than or equal to 20 mm). There was no correlation between the volume of pleural effusion and the intensity of tuberculin reaction. In patients more than 60 years of ages, the positivity was low (76.0%). The erythrocyte sedimentation rate (after 1 hour) was 63.6 +/- 31.6 mm. CLINICAL SYMPTOMS: cough in 72%; sputum in 48.5%; chest pain in 57.5%; tubercle bacilli in sputum in 11.6%. We compared idiopathic pleurisy (I) and secondary pleurisy (S) and total cases of pleurisy (T) regarding several factors; average age (I: 46.7, S: 48.0, T: 47.2); peak season of incidence (I: Feb. Mar. S: Mar. April, T: Feb. Mar. April); the period of hospitalisation (I: 4.07 months, S: 5.80 months, T: 4.77 months); the positive rate of tubercle bacilli in the pleural effusion (I: 9.0%, S: 12.9%, T: 10.5%); %VC (mean value) on admission (I: 71.4%, S: 69.8%, T: 70.7 +/- 17.0%); %VC after treatment (I: 79.0%, S: 79.7%, T: 79.4 +/- 17.9%), and we found no significant difference in the above factors between I. and S. In 49 patients who were treated by chemotherapy with steroids, %VC before treatment was 68.9% (mean value), and that after treatment was 81.2% (mean value), however, there was no significant difference between the %VC of these patients and that of total patients. Recent chemotherapy (SM or EB + INH + RFP) greatly contributed to improve clinical symptoms by accelerating the absorption of pleural effusion and in minimizing the formation of pleural thickening. Previously, we experienced often deterioration of tuberculous lesions in relation to the use of steroids. By the use of recent intensified chemotherapy, the harmful side effects of steroids became almost insignificant, and at the same time, treatment with steroids is needed only in a few cases. PMID- 2191168 TI - Further studies of enhanced growth of pancreatic carcinoma in diabetes. AB - Clinical studies suggest that pancreatic cancer occurs more often in persons with diabetes mellitus [1-7]. We have previously shown that the hamster pancreatic carcinoma cell line H2T grows more rapidly when implanted in streptozotocin (STZ) diabetic hamsters [8]. To determine if enhanced growth of pancreatic carcinoma cells in diabetic hamsters is due to polyphagia associated with diabetes, H2T cells were implanted into the cheek pouch of three groups of animals: normal hamsters (group I), STZ-diabetic hamsters (group II), and STZ-diabetics pairfed to normals (group III). Tumor weights 30 days after implantation were 172 g in group I, 368 g in group II, and 369 g in group III (P less than 0.007). There was no significant difference between the two diabetic groups. Thus, STZ diabetes appears to promote the growth of pancreatic carcinoma cells by a mechanism other than increased nutrient intake by diabetic tumor hosts. PMID- 2191169 TI - Changes in insulin receptors on methylcholanthrene-induced sarcoma during growth. AB - Methylcholanthrene-induced sarcomas (MCA-S) have different growth patterns in diabetic (D) and nondiabetic (ND) rats. Diabetes delays the early phase of tumor growth and prolongs survival. This study evaluated MCA-S growth and its relation to insulin receptors (IR) and glucose uptake. Fisher 344 rats 150-200 g were assigned to two groups: Diabetic tumor bearers (DTB, n = 26) and nondiabetic tumor bearers (NDTB, n = 18). Diabetes was induced with iv streptozocin (40 mg/kg); MCA-S was inoculated (1 X 10(6) cells) subcutaneously 10 days later. Animals were sacrificed during early growth (tumor volume less than or equal to 20 cc) or logarithmic growth (tumor volume greater than 20 cc). IR assay was performed (0-10(5) ng/ml cold insulin, 25 X 10(3) cpm/tube A14 125I-insulin, 90 min, 15 degrees C, pH 7.8) on a single cell preparation. Serum glucose milligrams per deciliter and insulin nanograms per milliliter were assayed. Glucose uptake (dpm/g tissue/hr) was assayed 2 hr after an ip injection of 0.5 microCi 3 O[14C]methylglucose. Diabetic, tumor-bearing animals had a significantly increased number of insulin receptors at the small [less than or equal to 20 cc, 28.7 (D) vs 8.3 (ND)] and large [greater than 20 cc, 82.8 (D) vs 27.8 (ND)] tumor volumes. Glucose uptake was increased in the tumor at both volumes in the non diabetic animals compared to the diabetic animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2191170 TI - Hepatic protein synthesis in a modified septic rat model. AB - The aim of this study was to develop a reproducible and sustained sepsis model in rats, lasting 3-4 days and characterized by appropriate metabolic changes, including increased hepatic protein synthesis, consistent with an acute-phase response. The rat cecal ligation and puncture (CLP) model was modified by decreasing the size and number of cecal punctures and increasing fluid resuscitation, which resulted in a 60% survival rate at 96 hr compared to 20% for standard CLP. Cultures of blood and peritoneal fluid 96 hr following induction of sepsis were positive in all septic animals with a mixed aerobic and anaerobic flora but with predominant growth of Escherichia coli. Septic rats demonstrated increased serum lactate levels and leukocytosis, while serum glucose and resting energy expenditure were not different from controls. Hepatic protein synthesis, measured in vivo by flooding dose technique, was increased by 74% in septic animals. Synthesis of the acute-phase proteins alpha 1-acid glycoprotein, complement component C3, and transferrin, measured by incorporation of [14C]leucine into proteins during a 120-min isolated liver perfusion, was increased twofold in septic animals. The present modified CLP model in rats may be useful in studies on the regulation of acute-phase protein synthesis during prolonged sepsis and in experiments aimed at modulating the septic response in liver by different treatments. PMID- 2191171 TI - Experimental studies on the healing of colonic anastomoses. AB - The leakage of colonic anastomoses is a potentially devastating surgical complication. Several factors, such as bowel preparation prior to surgery, surgical technique, nutritional status, and intervening pathological conditions, have been identified as significantly influencing the healing of colonic anastomoses. Due to the multifactorial nature, it is difficult to investigate the mechanisms of occurrence and prevention of colonic dehiscence in the clinical setting. For this reason, many experimental models have been used to study colonic healing and the pathogenesis of anastomotic failure. This report reviews the use of animal models for the study of colonic anastomotic healing. Special emphasis is devoted to the rationale for selecting animal models, parameters of healing, factors influencing anastomotic healing as well as the clinical potential of dietary and pharmacologic manipulations proposed to improve colonic healing. PMID- 2191172 TI - Quantitation of human melanoma, carcinoma and sarcoma tumor cell adhesion to lymphatic endothelium. AB - We have used an in vitro adhesion assay to study the interaction of tumor cells with lymphatic endothelium, a dynamic event that leads to tumor metastasis in vivo. 3H-thymidine-labeled human tumor cells from: one primary Ewing sarcoma, two established melanoma cell lines, two colon and two breast carcinomas (one established line and one primary culture of each) were added to 24-well culture dishes containing confluent monolayers of bovine lymphatic endothelium. Radioactivity associated with either the cells in suspension or the attached cells was assessed and compared at frequent intervals up to 360 minutes. Generally, tumor cell attachment increased as a function of time reaching a plateau between 180 and 360 minutes. the modular media system described here facilitates the primary and secondary culture (or co-culture) of a variety of normal and transformed cells. Primary cultures with a rounded morphology (one breast and one colon carcinoma) showed the lowest preferential attachment for lymphatic endothelium. All established cell lines and the primary Ewing sarcoma cell line displayed a more fibroblastic morphology and achieved the highest adhesion profiles. There was a correlation between the malignancy and attachment potential for the melanoma and breast carcinoma cell lines. Collectively, these data show that established tumor cell lines with fibroblastic-like morphology exhibit more rapid adhesion than primary tumor cell cultures with more rounded morphologies. While this property may reflect in vitro selection and/or adaptation, it does correlate with the metastatic propensity for some human tumor cells. PMID- 2191173 TI - Effect of the calcium antagonist nicardipine on the pressor action of endothelin. AB - To evaluate hemodynamic actions of endothelin, anesthetized normal dogs and dogs with two doses of nicardipine received endothelin (400 pmol/kg, i.v.). Normal dogs showed an increase in blood pressure (BP) associated with an early (5 min) increase in cardiac output (CO) and a later (60 min) increase in total peripheral resistance (TPR). The lower dose of nicardipine (0.01 mg/kg/h) abolished the latter vasoconstrictive BP elevation. Dogs with the higher dose of nicardipine (0.1 mg/kg/h) did not show any changes in BP, CO or TPR. Thus, endothelin has both cardiostimulatory and vasoconstrictive actions, depending on the degree of calcium influx. PMID- 2191174 TI - Biopharmaceutic aspects of buccal absorption of insulin. AB - Absorption of insulin through buccal mucosa was investigated using rabbits as animal model. The effects of various dose sizes, pH of the insulin solutions and a series of sorption enhancers or absorption promoters on the hypoglycemic response were studied using a buccal cell. In the absence of sorption promoters, the various dose sizes and pH of the administered insulin solution did not show any significant hypoglycemic response, indicating that substantial amounts of insulin were not absorbed through the buccal mucosa. In the presence of sorption enhancers, the extent of hypoglycemia was significantly enhanced in terms of AUC and Cmax. Among the sorption enhancers investigated, Brij 35 was the most satisfactory one, followed by sodium taurocholate, sodium laurylsulfate, sodium deoxycholate, sodium methoxysalicylate, sodium dextransulfate and EDTA. An inverse correlation was found between extent of hypoglycemia and light scattering intensity of insulin solution. The extent of hypoglycemia in presence of Brij 35 was concentration-dependent although a plateau was observed at high concentration range. The maximum pharmacological availability obtained from buccal administration of insulin solution was about 12%, while that obtained with the tablet formulation was about 4.3%. PMID- 2191175 TI - Pathophysiological role of endothelin in acute renal failure. AB - In conscious rats, the i.v. injection of endothelin (ET) caused an increase in blood urea nitrogen (BUN), an index of renal dysfunction. In the model of acute renal failure which was induced by occlusion of the bilateral renal arteries of rats followed by reperfusion, ET-monoclonal antibody improved the renal function. In this model, ET-antibody also protected the kidneys from renal proximal tubular necrosis and suppressed Ca++-accumulation in necrotic tissues. Plasma ET level increased 5 min and 5 hr and renal ET content did 5 and 20 hr after reperfusion. BUN level increased 5 and 20 hr after reperfusion. These results strongly suggest that the endogenously increased ET may be one of the important deleterious mediators in the pathogenesis of ischemic acute renal failure. PMID- 2191176 TI - Intrauterine neuromuscular blockade in fetus. AB - Antenatal intrauterine fetal therapy has now become the target of numerous invasive diagnostic and therapeutic maneuvers. Fetal motion during intrauterine fetal therapy not only makes these procedures technically more difficult but also increases the likelihood of trauma to the umbilical vessels and the fetus. Combination of high doses of sedatives, tranquilizers, and narcotics rarely results in adequate suppression of fetal movement. Such medication puts the mother at risk of respiratory depression, regurgitation and aspiration. The use of pancuronium or atracurium to temporarily arrest fetal movement in ten fetus is reported. After an initial ultrasound assessment of fetal lie, placental location, and umbilical cord insertion site, the fetal weight was calculated by the ultrasound parameters of biparietal diameter and abdominal circumference. Under ultrasound guidance, we injected pancuronium 0.15 mg/kg or atracurium 1.0 mg/kg using a 23-gauge spinal needle into the fetal gluteal muscle. Short-term paralysis of the fetus was induced in all cases. Fetal movement stopped by sonographic observation within 5.8 +/- 2.3 min in the pancuronium group and 4.7 +/- 1.8 min in the atracurium group. Fetal movements returned both to maternal sensation or ultrasonic observation by 92 +/- 23 min in the first group and 36 +/ 11 min in the second group. No adverse effect of the relaxant has been observed in any of the mothers. There was no evidence of local soft tissue, nerve or muscle damage at the site of injection on initial examination of the neonates after delivery. The use of neuromuscular relaxant in fetus was a safe and useful method. PMID- 2191177 TI - [Use of intraspinal narcotics in obstetric anesthesia and analgesia]. AB - The use of intraspinal narcotics has attracted great interest worldwide, particularly in the discipline of obstetric anesthesia. As the advent of spinal and epidural local anesthetics dramatically effected the anesthetic management of labor, delivery and obstetric surgery, likewise spinally administered opioids are emerging as safe and very effective methods of relieving post-cesarean section pain, improving labor and cesarean section analgesia in combination with local anesthetics, and injected alone in the subarachnoid space for the management of labor itself. Though intraspinal narcotic analgesia is associated with a number of side effects, with proper knowledge these adverse reactions are wither preventable or can be greatly reduced. Compared to the benefits of nearly complete pain relief in the intrapartum and postpartum periods, the price paid in terms of these side effects in minimal. The review was based on a computer assisted search for articles published after 1975. PMID- 2191178 TI - Why MEM does not work in MR image reconstruction. AB - This paper discusses the theory and application of the Maximum Entropy Method (MEM) to the reconstruction of Magnetic Resonance (MR) images. It is shown that the MEM is inappropriate for MR image reconstruction and that the usual heuristic justification is invalid in this case. The application of the MEM in MR image reconstruction is characterized as merely one of many constrained regularization approaches. PMID- 2191179 TI - CNR enhancement in the presence of multiple interfering processes using linear filters. AB - Given several images of the same slice, a linear filter can produce an image in which the contrast-to-noise ratio (CNR) between pathological and normal tissues is greater than in any of the initial images. To distinguish the pathology from more than one tissue, the filter should optimize the set of CNRs between the pathology and each of the interfering tissues. We define the optimal filter as the one which provides the largest value for the minimum CNR in the set and show how it is selected from a field of only four possibilities. The filter is demonstrated with both experimental phantom studies and clinical cases. Filter performance is compared with that of other techniques for distinguishing a desired feature from more than one interfering process. PMID- 2191180 TI - Constraints in chromosomal inversions in Escherichia coli are not explained by replication pausing at inverted terminator-like sequences. AB - Regions close to the replication terminus of the Escherichia coli chromosome are strongly refractory to genomic inversions. Since these regions also harbour polar replication terminator-like sequences or pause sites, we have investigated the possibility that slowing of replication as a result of pausing at inverted pause sites is responsible for inability to isolate stable inversions affecting these regions. A mutation in the tus gene is known to abolish replication pausing at terminators. We show here that the distribution of invertible and noninvertible segments along the chromosome is not affected by tus mutations. This observation eliminates replication pausing as a cause for the reduced fitness of bacteria harbouring certain chromosomal inversions. PMID- 2191181 TI - The purine-cytosine permease gene of Saccharomyces cerevisiae: primary structure and deduced protein sequence of the FCY2 gene product. AB - A 2.1 kb DNA segment carrying the purine-cytosine permease gene (FCY2) of Saccharomyces cerevisiae was sequenced, the primary structure of the protein (533 amino acids) deduced and a folding pattern in the membrane is proposed for the permease protein. Expression of the FCY2 gene product requires a functional secretory pathway and is reduced in mnn9, a mutant strain deficient in outer chain glycosylation. The FCY2 gene was mapped on the right arm of chromosome V close to the HIS1 gene. PMID- 2191182 TI - Mechanism for induction of adaptive mutations in Escherichia coli. AB - When bacterial cells are subjected to a strong selective pressure it often induces specific mutations. Here a model is considered in which errors are introduced at random in one of the strands of the DNA molecule: a nick in one of the strands can initiate strand displacement rendering a region of the chromosome single-stranded. Upon conversion back to double-stranded DNA there is a certain probability of introducing errors creating a heteroduplex. If an error results in the production of an mRNA molecule encoding a product which provides a selective advantage, growth will be stimulated and the mutation can be immortalized by chromosomal replication. Otherwise, the error can be corrected by the DNA 'proof reading' enzymes. PMID- 2191183 TI - The cytotoxic protein YopE of Yersinia obstructs the primary host defence. AB - It has previously been shown that the plasmid-encoded YopE protein of Yersinia pseudotuberculosis is a virulence determinant. In this study, HeLa cells, macrophages and mice were used as different model systems to determine the actual role of YopE in the virulence process. The YopE protein mediates a cytotoxic response on a confluent layer of HeLa cells. A prerequisite of this activity is that the pathogen binds to the cell surface. YopE also induces a cytotoxic response on mouse macrophages where it influences the ability of the pathogen to resist phagocytosis. Bacterial mutants defective in their ability to express YopE are avirulent after oral or intraperitoneal infection but virulent following intravenous injection. On the basis of these results, we propose a role for YopE in the virulence process of Yersinia. PMID- 2191184 TI - Ureaplasma urealyticum urease genes; use of a UGA tryptophan codon. AB - Nucleotide sequence analysis of a Ureaplasma urealyticum DNA fragment, homologous to cloned urease genes of other prokaryotes, revealed three consecutive open reading frames. The molecular weights of the three deduced polypeptides are 11.2 kD, 13.6 kD and 66.6 kD. These values are consistent with the size of the three subunits previously reported for purified native urease. A significant sequence homology was found between the three polypeptides of the ureaplasmal urease and the single polypeptide of jack bean (Canavalia ensiformis) urease. Codon usage indicates that UGA is a tryptophan codon in this mollicute. Use of polymerase chain reactions has disclosed the existence of genetic polymorphism among the urease genes of different serotypes of U. urealyticum. PMID- 2191185 TI - Suppressive effect of glucose administration on the binding of prolactin by rat liver. AB - In an attempt to elucidate the physiologic role of the hepatic receptors for prolactin (PRL), we studied the effect of changes in diet on the specific binding of 125I-ovine prolactin (oPRL) by membranes from female rat liver. Specific binding of PRL (SBP) was decreased by over 50% in rats fed 15% glucose ad lib for 2 days, as compared with fasted rats (P less than .01), while serum PRL was similar in both groups. Feeding 20% glucose by tube decreased SBP significantly, but tube-feeding equicaloric amounts of fat or protein-amino acid solution did not. Glucose feeding did not decrease the specific binding of 125I-bovine growth hormone (bGH) to liver, or decrease SBP to membranes of nitrosomethylurea (NMU) induced mammary carcinomas, indicating that the effect of glucose on hepatic SBP is selective. Administration of glucose decreased SBP significantly in adrenalectomized-ovariectomized rats, in adrenalectomized-chemically sympathectomized rats, and in hypophysectomized rats receiving replacement therapy, including bovine prolactin (bPRL), bGH, hydrocortisone, estrogen, and thyroid hormones. Thus, the effect of glucose is not mediated by a factor from the adrenals, ovaries, or pituitary, and probably not by catecholamines. Administration of insulin to fasted diabetic rats did not alter SBP. Infusion of glucagon for 1 day, at a rate that did not alter serum glucose, increased hepatic SBP 29% (P less than .01). Since glucose administration decreases plasma glucagon, we hypothesize that glucagon may contribute to the maintenance of the hepatic PRL receptors, and that the suppressive effect of glucose on hepatic SBP may be mediated at least in part by suppression of plasma glucagon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2191186 TI - Correlates of plasma very-low-density lipoprotein concentration and composition in premenopausal women. AB - Potential correlates of plasma very-low-density lipoprotein (VLDL) concentration and composition were studied in a sample of 75 premenopausal women. Fasting plasma free fatty acid (FFA) levels, as well as plasma glucose and insulin levels in the fasting state and during an oral glucose tolerance test, displayed significant positive correlations with plasma triglyceride (TG) and VLDL-TG levels (P less than .005). Plasma post-heparin lipoprotein lipase (LPL) activity, measured in a subsample of 31 women from the original sample, was negatively correlated with plasma TG, VLDL-cholesterol (CHOL), VLDL-TG, and VLDL apolipoprotein (apo) B concentrations (.005 greater than P less than .05). Multivariate analyses showed that, after LPL was considered, the insulin area was the only other metabolic variable studied that was significantly correlated with VLDL-apo B concentration, whereas fasting FFA levels were significantly correlated with plasma TG and VLDL-TG levels. ANOVA revealed that plasma VLDL CHOL, VLDL-TG, and VLDL-apo B levels were not associated with the glucose area, but were significantly associated with the insulin area (P less than .005). When the effect of insulin area was controlled for, the plasma FFA levels did not contribute significantly to the variance in VLDL-CHOL and VLDL-apo B, but showed an independent effect on VLDL-TG levels (P less than .05). Finally, stepwise multiple regression analyses indicated that once the variance explained by plasma LPL activity and by the insulin area was considered, no other metabolic variable could account for the variation in VLDL-CHOL and VLDL-apo B levels, whereas fasting FFA levels explained a further 5% of the VLDL-TG variance and one third of the variance observed in the VLDL-TG/apo B ratio.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2191187 TI - The effect of ethanol infusion on the altered glucose turnover during bacterial infection. AB - The increased glucose turnover seen during the hypermetabolic, hyperdynamic phase of sepsis is part of the body's defense mechanisms. In contrast, the metabolism of ethanol (ETOH) is known to compromise hepatic gluconeogenesis under certain conditions. This study tested the hypothesis that acute infusion of ETOH inhibits the elevated glucose production that is manifested during infection and thereby alters the normal responses to sepsis. In catheterized conscious rats, ETOH or saline infusion was started 24 hours before the induction of sepsis, and continued throughout the experiment. In vivo glucose kinetics were assessed by the infusion of [6-3H, U-14C]-glucose 24 hours after the induction of sepsis. The characteristic sepsis-induced hyperthermia was prevented in ETOH-infused animals. Sepsis increased the plasma lactate concentration (100%), as well as the rates of glucose appearance ([Ra] 77%), recycling (213%), and metabolic clearance ([MCR] 82%) in saline-infused control animals. In contrast, ETOH infusion prevented the sepsis-induced increase in glucose Ra and markedly attenuated the increase in plasma lactate (49%) and glucose recycling (97%). The infusion of ETOH increased the lactate/pyruvate and beta-hydroxybutyrate (BHBA)/acetoacetate (AcAc) ratio in both septic and nonseptic rats. These results indicate that ETOH administration attenuates the increased glucose production, utilization, and elevated arterial lactate, and prevents the hyperthermic response seen during the hypermetabolic phase of sepsis. Thus, ethanol intoxication alters the normal metabolic responses to sepsis, thereby contributing to the compromised host defenses against the challenging bacteria. PMID- 2191188 TI - Hyperglycemia per se can reduce plasma free fatty acid and glycerol levels in the acutely insulin-deficient dog. AB - To evaluate the in vivo effect of hyperglycemia per se on plasma free fatty acid (FFA) and glycerol concentrations, euglycemic and hyperglycemic clamp studies were performed in six overnight fasted dogs in the state of insulin deficiency produced by somatostatin (SRIF) infusion. The mean blood glucose concentrations during the steady-state (the second hour of each study) averaged 4.65 +/- 0.10 mmol/L in euglycemic clamp and 14.11 +/- 0.10 mmol/L in hyperglycemic clamp. During the SRIF infusion, plasma FFA concentrations increased from 0.32 +/- 0.05 mumol/mL at the basal state to 0.76 +/- 0.04 mumol/mL at the steady-state in euglycemic clamp and from 0.26 +/- 0.04 mumol/mL to 0.43 +/- 0.02 mumol/mL in hyperglycemic clamp. Plasma glycerol concentrations increased from the basal value of 0.07 +/- 0.01 mumol/mL to 0.15 +/- 0.01 mumol/mL during the steady-state in euglycemic clamp and from 0.06 +/- 0.01 mumol/mL to 0.08 +/- 0.01 mumol/mL in hyperglycemic clamp. The steady-state concentrations of plasma FFA and glycerol in hyperglycemic clamp were significantly lower than those in euglycemic clamp (P less than .001; respectively). These results suggest that hyperglycemia per se might decrease plasma FFA and glycerol concentrations at least in part by decreasing lipolysis in the acutely insulin-deficient dog. PMID- 2191189 TI - Effects of intraperitoneal versus subcutaneous insulin administration on lipoprotein metabolism in type I diabetes. AB - In order to compare the effects of intraperitoneal (IP) versus subcutaneous (SC) insulin delivery on plasma lipoproteins, lipoprotein cholesterol, triglycerides, and very-low-density lipoprotein (VLDL) metabolism were compared in five type I diabetic patients while they were receiving continuous IP insulin (CIPII) or continuous subcutaneous insulin infusion (CSII). Each therapy regimen was of at least 1 month duration, and patients were treated in random order. Mean daily plasma insulin was lower on CIPII compared with CSII. CIPII was associated with lower VLDL triglycerides and VLDL apolipoprotein (apo) B, and higher high-density lipoprotein (HDL) and HDL3 cholesterol. The decreased VLDL on CIPII appeared to be the result of both decreased production and increased clearance of VLDL apo B. The results suggest that the more physiologic route of insulin therapy (CIPII) is associated with lipoprotein profiles of lower atherogenic potential. PMID- 2191190 TI - Compensatory capabilities of islets of BB/Wor rats exposed to sustained hyperglycemia. AB - To determine if discordance for autoimmune diabetes in genetically homogeneous animals might reflect differences in the compensatory capacity of their beta cells, the glycemic responses of diabetes-prone BB/Wor rats during a high rate infusion of 50% glucose were compared with normal and with 40% pancreatectomized Wistar rats similarly infused. In all three groups, the initially severe hyperglycemia declined after the first 48 hours to below the target level of 300 mg/dL despite an increasing rate of glucose infusion. The glycemic profile did not differ from controls and was lower than that of the partially depancreatized rats. Five of 20 hyperglycemic BB/Wor rats became diabetic during the 12-day infusion of 50% glucose; there was no difference between their glucose profiles and those of the 15 prediabetic BB/Wor rats that remained nondiabetic throughout the period of hyperglycemic infusion. The latter group of BB/Wor rats, many of which would ultimately have become diabetic, exhibited a 2.4-fold increase in the volume density of their beta cells, compared with a 2.1-fold increase in the Wistar controls. This clinical and morphologic evidence of beta-cell compensation in diabetes-prone rats, even in on the verge of overt diabetes, excludes the possibility that subnormal compensation by beta cells contributes to diabetes in the BB/Wor rat. PMID- 2191191 TI - Oral and intravenous glucose-induced insulin secretion in hyperthyroid patients. AB - To elucidate glucose intolerance in hyperthyroidism, insulin response to oral (75 g) and intravenous (IV) (20 g) glucose administration was investigated in 18 hyperthyroid patients and six normal control subjects. In oral glucose tolerance tests (OGTT), plasma insulin and C-peptide levels in hyperthyroid patients were not significantly different from that in controls; however, an impaired blood sugar response was observed in hyperthyroid patients. In IVGTT, blood sugar, plasma insulin, and C-peptide levels were significantly higher in hyperthyroid patients than in controls. Insulin secretion in proportion to blood sugar stimulus (the sum of increment in insulin divided by the sum of increment in blood sugar after glucose load, sigma delta IRI/sigma delta BS) in IVGTT was similar in hyperthyroid patients and controls; however, that in OGTT was significantly lower in hyperthyroid patients. After thyroid function tests had returned to normal by treatment with thiamazole, glucose tolerance and sigma delta IRI/sigma delta BS in OGTT were almost normalized. These results indicate that decreased insulin secretion after oral glucose may have an important role in abnormal oral glucose metabolism in hyperthyroidism. PMID- 2191192 TI - Influence of glucocorticoids on skeletal muscle proteolysis in normal and diabetic-adrenalectomized eviscerated rats. AB - The effect on skeletal muscle proteolysis of acute (20-hour) glucocorticoid treatment (dexamethasone 1.5 mg/kg, subcutaneously [SC]) was tested using the eviscerated rat preparation. According to this method, the peripheral tissues (primarily the skeletal muscles) are isolated by functional hepatectomy nephrectomy. Total proteolysis is estimated from the rate of rise of plasma tyrosine concentration in the presence of cycloheximide to block protein synthesis. Myofibrillar proteolysis is measured from the rate of release into the plasma of the nonreutilized, nonmetabolized amino acid 3-methylhistidine (3MH), in the absence of cycloheximide. In normal rats, dexamethasone increased total proteolysis by 20% and myofibrillar proteolysis by 75% (both P less than .025 v saline controls). In diabetic-adrenalectomized rats prepared 2 weeks earlier (65 mg/kg streptozocin [STZ] followed by adrenalectomy), dexamethasone caused much greater increments in rates of total proteolysis (94%) and myofibrillar proteolysis (240%) (both P less than .001 v saline controls). Because diabetic animals are extremely sensitive to glucocorticoid-induced proteolysis, we also examined whether the acute proteolytic effect of diabetes itself might be mediated by adrenal cortical hormones. Previously adrenalectomized rats studied 20 hours after STZ showed a 40% augmentation of total proteolysis (P less than .01), an effect similar to that produced by acute diabetes in rats with intact adrenals. We conclude that glucocortical hormones cause a catabolic effect on total and myofibrillar skeletal muscle protein which is exaggerated when the counteracting action of insulin is reduced, but that the excess proteolysis of acute insulin deficiency is independent of the endogenous glucocorticoids secretion. PMID- 2191194 TI - Ultrastructural features of host-parasite interactions in "in vitro" cultures of Plasmodium falciparum. AB - We carried out an electron-microscopy study on in vitro cultures of Plasmodium falciparum, whose general ultrastructural features are consistent with previous reports. In addition, whorled membrane-vesicles systems involving parasite and host-cells, never described to our knowledge up to now. As far as the parasite is concerned, these membraneous systems appear to be related to its growth and its connection with the external medium, with the possible involvement of Maurer's clefts. As for the erythrocyte, surface vesicles prove to be related to plasmodial infection in long-term in vitro culture. Richness in membranous structures of the complex host-parasite varies according to the metabolic demand of the plasmodium (i.e. on the life-cycle stage) and is influenced by external factors, possibly being a marker of drug action. PMID- 2191193 TI - Microbial mutagenicity screening of natural flavouring substances. AB - Sixty-five commercial samples of natural flavouring substances were screened for mutagenicity in the Salmonella typhimurium strains TA98 and TA100. The results obtained demonstrated a significant mutagenic activity in onion and garlic extracts, both in assays with and without exogenous metabolic activation. The response pattern obtained in tester strains with different genetic backgrounds suggests the involvement of mutagenic flavone(s) in the genotoxic effects observed. PMID- 2191195 TI - Human immunodeficiency virus type 1 antigen detection in endomyocardial biopsy: an immunomorphological study. AB - A virological and immunomorphological study has been performed on endomyocardial biopsy from an AIDS patient. Some data suggest the possible involvement of HIV in the pathogenesis of the cardiomyopathy. PMID- 2191196 TI - Growth of opportunistic yeasts on vitamin-free solid medium. AB - The growth of some opportunistic yeasts (Candida albicans, Cryptococcus neoformans, Torulopsis glabrata, Rhodotorula rubra, Geotrichum candidum, Trichosporon cutaneum, Saccharomyces cerevisiae) was essayed in a solid minimal synthetic medium without vitamins. From the preliminary results some species (Candida albicans, Cryptococcus neoformans, Rhodotorula rubra, Geotrichum candidum and Saccharomyces cerevisiae) seem to be autotrophic regarding the growth factor considered indispensable for their metabolism and for this reason normally added to the common synthetic media employed. PMID- 2191197 TI - Relationship between Mg2(+)-induced hexagonal assembly of R-form lipopolysaccharides and chemical structure of their R-cores. AB - The relationship between formation of the Mg2(+)-induced hexagonal lattice structure by R-form lipopolysaccharides (LPS) and chemical structure of their R cores was investigated using different kinds of R-form LPS from a series of mutants of Salmonella minnesota or S. typhimurium. The optimal experimental condition for formation of the hexagonal lattice structure was to suspend LPS preparations, from which cationic material was removed by electrodialysis, in 50 mM tris (hydroxymethyl) aminomethane buffer at pH 8.5 containing 10 mM MgCl2. Under this experimental condition, Rb1 LPS formed the hexagonal lattice structure with the lattice constant of 14.0 +/- 0.2 nm. Ra LPS, which possesses the full length of R-core, also formed the hexagonal lattice structure but its lattice constant was larger (18.1 +/- 0.2 nm) than that of Rb1 LPS (the lattice structure by Ra LPS was looser than that by Rb1 LPS). All the other R-form LPS preparations tested, RcP+, PcP-, Rd1P-, and Re LPS, whose R-cores are shorter than that of Rb1 LPS, did not form the hexagonal lattice structure, but formed membranous structures showing various shapes which consisted of multiple bilayer structures. Failure to form the hexagonal lattice structure was the common feature of these kinds of R-form LPS irrespective of temperature at which the LPS suspensions in 10 mM MgCl2-50 mM Tris buffer were incubated. From the results of the present study it was concluded that capability of R-form LPS to form the hexagonal lattice structure has a close correlation with the chemical structure of their R cores. PMID- 2191198 TI - [The antilysozyme activity of bacteria in the genus Klebsiella]. AB - The ability to inactivate lysozyme was found in representatives of three species of the genus Klebsiella bacteria: K. pneumoniae (117 strains), K. rhinoscleromatis (104 strains), K. ozaenae (90 cultures). The test cultures displayed a different antilysozyme activity, inactivating from 2 to 30 micrograms/ml of the enzyme. Taking into account the lysozyme role in the immunity and chitin synthesis processes in the organism of insects, the inactivation of the enzyme by Klebsiella may be considered as one of possible mechanisms of the entomopathogenic action of these bacteria. PMID- 2191199 TI - [An evaluation of the DNA-damaging action of the metal carcinogen beryllium using a bacterial repair test]. AB - Using four strains of E. coli with different DNA repairing capacities it was established that beryllium efficacy in the DNA repair test (extension inhibition zone and the lowest concentration inhibiting bacterial growth) depended on pH of the medium and the cation, anion concentration and the metal acted bacteriostatically. A conclusion was made that in the given case the repair test detected the nonidentified membrane function of the DNA repair system, possibly associated with the usage of exogenous orthophosphate rather than the repair synthesis in response to DNA damage by beryllium. PMID- 2191200 TI - [A comparative study of the IgG-binding components of the membrane in different strains of Staphylococcus aureus using the indirect hemagglutination reaction and an immunofluorescence method]. AB - A comparative estimation of IgG-binding activity of 85 S. aureus clinical strains was carried out by the method of indirect hemagglutination reaction. The S. aureus strain selected as a result of screening was found to exceed by more than an order the Cowan I strain obtained from the L. A. Tarasevich State Institute of Standards and Control of the Medical Biological Drugs in the IgG-binding activity. It was established that the ratio of two types of IgG-binding sites located on the S. aureus surface, varied depending on the strain, composition and quality (liquid or solid) of the culture medium. PMID- 2191201 TI - [The absence of an action of the pyrethroids deltamethrin and cypermethrin on mosquito susceptibility to the causative agent of malaria]. AB - Mosquitos Ae. aegypti and An. stephensi contact with sublethal doses of deltametrin and cypermetrin pyretroids at larval stage and in grown state, when diet includes sugar with pyretroids, had no influence on the sensitivity of survived females to malaria agents P. gallinaceum and P. berghei. Mosquitos under experiment showed no obvious inhibition of the physiological condition in comparison with the control ones. PMID- 2191203 TI - [An evaluation of different methods for making vital preparations for the detection of Borrelia in ixodid ticks]. AB - Comparative assessment of suitability of darkfield microscopy of the preparation from the ticks dissected by needles in a drop of saline for evaluation of spontaneous infection rate of unfed imago ticks--vectors of Lyme disease--has been made, by using Ix. persulcatus and Ix. ricinus collected in Leningrad Province as models. Examination of 100 individuals by parallel exploration of the glass-covered drops and the preparations from the middle intestine of the ticks demonstrated the presence of Borrelia in equal (28) cases. The material from 150 other dissected ticks has been examined concurrently in glass-covered and uncovered preparations. 44 infected vectors have been revealed in the first case and 35 in the second. The difference is due to incomplete detection of slightly infected individuals. PMID- 2191202 TI - [Malaria morbidity among the nonimmune foreigners in the city of Maputo and the problem of chemoprophylaxis]. AB - In a colony with nonimmune foreigners in Maputo city (Mozambique People's Republic) active detection and treatment of patients suffering from malaria has been carried out for 1.5 years. It was shown that even in a city with some hyper- and mesoendemic regions where less than 10% of colony members were treated with chemoprophylaxis, yearly morbidity among them did not surpass 20-30 cases per 1000 population. Such index is considered to be admissible risk for health if adequate diagnosis and treatment of infection is available. Despite predominance of drug-resistant strains of tropical malaria agents among the local population, resistance to chlorochin or phancidar was observed in 3 foreign patients out of 31. In one case the clinical pattern of infection was atypical. PMID- 2191204 TI - [Biotechnological approaches to the creation of antimalarial vaccines]. AB - The authors analyze the latest data on antigen pattern of malaria Plasmodium at various stages of development and extraction of immunogenic determinants contributing to creation of malaria vaccine. Knowledge of the spectra of Plasmodium antigens and stimulants of humoral and cellular immune response in the body will simplify the search for effective biotechnological vaccines able to provide reliable protection against malaria. PMID- 2191205 TI - [The centenary of the discovery of the causative agent of tropical malaria]. PMID- 2191206 TI - [Centenary of the birth of Petr Petrovich Popov]. PMID- 2191207 TI - [The 90th anniversary of the birth of Polina Andreevna Petrishcheva]. PMID- 2191208 TI - [Piezoelectric lithotripsy in the treatment of symptomatic gallstone patients]. AB - From January to May 1989, 50 patients with symptomatic gallstones were treated by means of extracorporeal piezoelectric lithotripsy combined with oral bile acid therapy. In 98% of all patients stone fragmentation was achieved. The mean number of treatment sessions per patients was 3.24. We observed as complications one gallbladder- and one liver hematoma each besides colicy pain and asymptomatic laboratory changes. Two patients developed mild pancreatitis and two a cholecystitis; three patients had symptomatic common bile duct stones during the follow-up. ERCP with endoscopic papillotomy was performed four times, one female patient had to undergo surgery due to an acute gallbladder. Three months after the first treatment, 18 patients (36%) were stonefree, six months later 54% (21/39). Patients with solitary stones up to 2 cm in size were in 71.5% stonefree respectively after three months. Thus, piezoelectric lithotripsy represents in our opinion a possible therapeutic modality for the treatment of symptomatic gall stones in selected patients. PMID- 2191209 TI - [Indications, technics and complications in endoscopic removal of polyps of the large intestine]. PMID- 2191210 TI - [Oral hormone therapy in pre- and postmenopause]. PMID- 2191211 TI - [Treatment of hypogonadism and infertility in the male. III]. PMID- 2191213 TI - Prescriptive rehabilitation for severely disabled psychiatric patients. AB - Several behavioral rehabilitation strategies have been empirically validated in the treatment of schizophrenia and are now the psychosocial treatments of choice for chronic mental disorders. The stress-vulnerability model and an empirically based decision tree offer clinicians' guidance in prescribing strategies that are particularly relevant for each patient. Hence, behavioral family therapy may be indicated for patients who experience disease exacerbation that results from stressful family interactions. Patients with insufficient social and coping skills may benefit from skills training. Supported employment and job-finding clubs may be indicated for patients with deficits in work skills. The form and programmatic matrix of these strategies differ, depending upon their locus in inpatient and outpatient settings. PMID- 2191212 TI - [Visceral leishmaniasis contracted in Europe (kala-azar)]. PMID- 2191214 TI - Multiple sclerosis program: a model for neuropsychiatric disorders. PMID- 2191215 TI - [Pathology of thyroid diseases in children]. AB - In the present survey the pathohistologic substrate of the major thyroid diseases (functional disturbances, goiters, inflammations, tumors) occurring in childhood is described. In this context the functional morphology (correlation of structure and function) and the immunohistology of the thyroid is reported in detail. Finally, it is discussed under which conditions histologic studies of the thyroid are meaningful for the diagnosis. PMID- 2191216 TI - [Conservative strategies in treating thyroid diseases in children]. AB - In the Federal Republic of Germany disorders of the thyroid gland are among the most common chronic diseases of childhood and adolescence. In Munich 30% of schoolchildren, in Gottingen 16% of children 6 to 16 years of age have goiters. Iodine deficiency is the most important etiological reason for the development of euthyroid goiter, which is encountered in more than 80% of children and adolescents suffering from thyroid disorders. Lymphocytic chronic thyroiditis (Hashimoto) causes goiters which may be eu-, hypo- but also hyperthyroid. Thyrotoxicosis (M. Basedow, Grave's Disease) in childhood occurs mainly in pubertal girls. The frequency of congenital hypothyroidism in West Germany is 1:3,800 neonates. The postnatally acquired hypothyroidism in childhood is as rare as hyperthyroidism caused by toxic thyroid adenoma. 27% of nodular goiters in childhood are due to Thyroid carcinoma. The diagnostic procedure of evaluation of thyroid disorders in childhood includes family and past personal history, palpatory findings, ultrasonography and the determination of TSH and thyroid hormone plasma concentrations. The aims of conservative management of thyroid diseases during childhood and adolescence are 1st normalisation of size of the thyroid gland, 2nd achievement and maintenance of euthyroid function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2191217 TI - [Natural science and humanitarian aspects of medicine]. AB - In the 19th century the natural sciences took a rapid rise, connected with a mainly biological interpretation of all vital processes. To the physician fell the role of the analytical observer who--according to the findings obtained - made a precise diagnosis which in consequence led to the adequate therapy. Patient and disease were the objects of observation and treatment. In the twentieth of our century a radical change took place. R. von Weizsacker and R. Siebeck established the "anthropologic medicine" resp. the "medicine of the person" where the doctor and the patient enter into a personal relationship. The significance of the patient's biography in the course of this disease was recognized. The "psychosomatic medicine" was developed. Our own time requires the reorientation to those values and principles and, moreover, and improved integration of the advanced medical technology. PMID- 2191218 TI - [Ultrasound changes of the pancreas in patients with mucoviscidosis]. AB - Pancreas sonography was performed on 171 patients with cystic fibrosis. The pancreas was visualized in 138 patients (81%) and could not be visualized in 33. 125 patients (90%) had abnormal echogenicity of the pancreas. Cysts were found in 5 patients. Two patients showed a dilatation of the pancreatic duct. The pancreas was abnormal in 98% of all patients aged more than 6 years. PMID- 2191219 TI - [Life-threatening perinatal hemorrhage of a sacral teratoma]. AB - Great sacral teratomas are rare congenital tumors. The frequency in liveborns is about 1:40,000. Well known complications of sacral teratomas are malignant degeneration, infection and, in case of intraabdominal expansion, compression of the urogenital tract. We report a case of unusual fulminant perinatal bleeding out of a great sacral teratoma ruptured during birth. PMID- 2191221 TI - Aspergillus fumigatus as a cause of mycotic tracheitis in a chicken. AB - An unusual case of mycotic tracheitis in a young chick caused by Aspergillus fumigatus was recorded from Anand, India, during 1987. The pathogen was demonstrated in the tracheal exudate by potassium hydroxide technique and also recovered from the trachea on Sabouraud dextrose agar at 37 degrees C. The characteristic hyphae of Aspergillus spp. were demonstrated in tracheal mucosa in histopathological sections stained by periodic acid Schiff method. Interestingly, the lesions were confined only to the trachea. Environmental investigations established the source of infection in the farm where the litter was highly contaminated with A. fumigatus. PMID- 2191220 TI - Detection of circulating galactomannan by Pastorex Aspergillus in experimental invasive aspergillosis. AB - The performance of Pastorex Aspergillus, a new latex agglutination test for the detection of circulating galactomannan in the serum of patients with invasive aspergillosis, was evaluated in a blind trial in standardized guinea-pig models of invasive aspergillosis and other invasive mycoses. In these animal models, the invasive nature of the fungal infection was confirmed by re-isolation of the etiologic agent from the organs of every animal. Ninety-two plasma samples from 42 animals with invasive aspergillosis were submitted to the test. In 41 of these animals, at least one plasma sample was positive with the latex test (sensitivity 97.6%), titers ranging from 1/1 to 1/512. In general, antigen titers increased as a function of time, reaching the highest values shortly before death. Guinea-pigs infected with Penicillium marneffei also yielded positive agglutination reactions but antigen titers were lower (maximal titer 1/8). Plasma samples from animals with invasive candidosis (23), disseminated trichophytosis (11) and cryptococcosis (23) were all negative with the latex test. In 80 guinea-pigs without fungal infection, 3 false positive results (titers 1/1) were observed, which means a specificity of 96.2% in this control group. PMID- 2191222 TI - Fungal flora of human faeces in psoriasis and atopic dermatitis. AB - Faeces samples taken from 343 patients with psoriasis and 581 patients with atopic dermatitis were subjected to mycological examination. Yeasts were detected in 68% of the psoriatics and in 70% of the patients with atopic dermatitis but in only 54% of the controls (n = 50). Qualitative analysis revealed a predominance of Candida albicans. Non-pathogenic yeasts constituted only 1% in each of these groups. Of the hyphomycetes, Geotrichum candidum occurred in 22% of the psoriatics, in 10% of the atopic dermatitis patients and in 3% of the controls. Aspergillus species were found in 1% of the patients but not in the controls. Stool samples collected on three consecutive days from 141 patients were examined for yeasts. Qualitative correlation between all three samples was shown in 95% of the patients and quantitative correlation in 38%. Deviations were mainly of exponential magnitude. Germ cell concentration of 10(4) cells per ml and above were measured in 38% of the psoriatics and in 28% of the atopic dermatitis patients but in only 22% of the test subjects with healthy skin. There was no correlation between the concentration levels of yeasts in the faeces and the extent of psoriasis or atopic dermatitis. PMID- 2191223 TI - T-2 toxin impairment of murine response to Salmonella typhimurium: a histopathologic assessment. AB - T-2 toxin and other trichothecene mycotoxins experimentally impair normal immune function and may predispose humans and animals to infectious disease. In this study, the histopathologic effects of Salmonella typhimurium challenge concurrently with sublethal T-2 toxin exposure were examined in the Salmonella resistant C3H/HeN mouse. Oral administration of T-2 toxin (1 mg/kg) every other day for 10 d had little effect on the tissues examined when compared to control animals. Mice challenged with S. typhimurium and then treated with T-2 toxin every other day for 10 d had markedly larger and more bacterial-related lesions in the spleens, kidneys, and livers than animals challenged with S. typhimurium alone. Differences in bone marrow, Peyer's patches and ileal tissues were less discernable between S. typhimurium and S. typhimurium plus T-2 toxin treated groups. These results were consistent with previous findings that T-2 toxin compromised murine resistance to S. typhimurium infection and ultimately caused death in animals challenged with a sublethal dose of the organism. PMID- 2191224 TI - Linen versus non-woven fabric drapes. PMID- 2191225 TI - [Herpes zoster and acyclovir in normal and deficient general immunity, also that due to AIDS]. PMID- 2191226 TI - [Hybrid cytochemistry; current possibilities for the detection and localization of nucleic acids in microscopic preparations]. PMID- 2191227 TI - [Dutch radiodiagnosis from an international viewpoint]. AB - A quantitative description of diagnostic radiology is given in terms of radiological density (the number of radiological examinations per 1000 inhabitants), consumption of roentgen film and contrast media. The data concerning examinations were recorded by a yearly inquiry system addressing all Dutch radiologists. The consumption of film and contrast media were derived from the data banks of the industries. In comparing these data with the data for Western Europe, Japan and the United States it is remarkable that diagnostic radiology scores lowest in regard to density, film consumption and use of contrast media. Only in the use of 35 mm cinefilm (coronary angiography) is The Netherlands number 2 on the list preceded by the United States. As a consequence radiation exposure of the population caused by diagnostic radiology is low in The Netherlands. Although the technical condition of the equipment is good due to regular and preventive service the life-span of the radiological equipment is gradually increasing beyond the limits of the normal economic depreciation. Growing arrears are found in the application of new technology: ultrasound, computer tomography and magnetic resonance imaging. The substitution of high osmolar contrast media by low osmolar media is also lagging behind. PMID- 2191228 TI - [New aspects of the pathogenesis and therapy of Guillain-Barre syndrome and chronic polyneuritis]. AB - The Guillain-Barre syndrome and chronic idiopathic polyradiculoneuropathy (CIDP) are examples of immune-mediated neuropathies. In the Guillain-Barre syndrome, antibodies directed to neutral glycolipids of peripheral nerve myelin have been detected that activate the complement system. There is evidence for the presence of circulating activated T lymphocytes. Humoral factors have been implicated in the pathogenesis of CIDP. The animal model experimental autoimmune neuritis lends itself to the elucidation of pathogenic immune mechanisms. The principal treatment is plasmapheresis. Further approaches to the therapy of the Guillain Barre syndrome and CIDP are discussed. PMID- 2191229 TI - [Extreme lateral lumbar intervertebral disk displacement. Incidence, symptoms and therapy]. AB - Upper lumbar nerve root compression or a femoralgia is often caused by extreme lateral lumbar disc herniation. This type of lumbar disc herniation compresses the nerve root inside or laterally to the intervertebral canal, while mediolateral disc herniations squeeze it in the lateral recess. Pain radiating obliquely over the thigh is the dominant clinical symptom. Bending the body to the ipsilateral side usually increases the pain. When neurologic signs are present, motor deficits tend to be more prominent than sensory and the deficits never affect more than one nerve root. Most frequently a weakness of knee extension occurs. PMID- 2191230 TI - Poststreptococcal glomerulonephritis. Current clinical and pathologic concepts. PMID- 2191231 TI - Long-term incidence of peritonitis in CAPD patients treated by the Y set technique: experience in a single center. AB - Our experience of peritonitis in 156 patients over an 8-year period represents 186 episodes of peritonitis and 4,964 patient-months of CAPD. The incidence of peritonitis was significantly greater (1 episode every 8.6 patient-months) when the Oreopoulos technique was used and dropped to 1 episode every 43.3 patient months when the Y set system was used. Of the 109 patients using the Y set system, 88 (80.7%) never had episodes of peritonitis, whereas only 7 (16.7%) of the 42 patients using the Oreopoulos technique were free of peritonitis. For 23 patients shifted from the Oreopoulos to the Y set technique, the incidence of peritonitis dropped from 1/9.8 to 1/35.2 episodes/patient-months. PMID- 2191232 TI - Hepatitis B virus-associated membraneous nephropathy: clinical features, immunological profiles and outcome. AB - To evaluate the clinical features, immunological profiles and the prognosis of hepatitis B virus-associated membraneous nephropathy (HBVMN), 34 patients (25 boys and 9 girls) were studied from April 1981 to November 1987. With Fab fragments of monoclonal antibodies, hepatitis B e antigen (HBeAg) was detected in the glomerular deposits from 30 cases (88.2%) and in the sera from 32 cases (94.1%). These results suggest that HBeAg plays an important role in the development of HBVMN. In addition, clinical trials of 32 cases demonstrate a relatively poor response to the steroid therapy with persistent heavy proteinuria (32.4%) or a high frequent relapse rate (38.2%); only 1 case (3.1%) had early response. In 4 cases follow-up renal biopsy was performed, progressive sclerosis with interstitial fibrosis being noted in each instance. The stage of membraneous nephropathy examined under the light microscope, had progressed from stage I or II to stage III. One had impaired renal function. Therefore, HBVMN does not always take a benign course. In the immunological profiles, significant hypocomplementemia with low C3, C4 and properdin factor B levels were found during the initial 6 months after the onset of disease. Hepatitis B surface antigen (HBsAg) circulating immune complexes (CIC) were also significantly higher. However, the levels of HBsAg CIC did not correlate with the degree of proteinuria or hematuria. In patients with persistent HBaAg carriage, serum HBeAg status alone did not correlate with remission rate, and remission occurred usually before the HBeAg seroconversion to anti-HBe. These results suggest that factors other than HBeAg play important roles in HBVMN. PMID- 2191233 TI - Treatment of rapidly progressive glomerulonephritis due to Behcet's syndrome with intravenous cyclophosphamide. AB - A patient with Behcet's syndrome developed hematuria, proteinuria, and rapidly progressive, severe, renal failure. Renal biopsy confirmed the presence of crescentic, necrotizing glomerulonephritis. Treatment with intravenous corticosteroids and oral cyclophosphamide (CTX) failed to arrest the decline in renal function. Intravenous pulse CTX was administered monthly for four treatment cycles with consequent improvement and stabilization of renal function, albeit at a markedly depressed glomerular filtration rate. The literature of case reports concerning crescentic glomerulonephritis in Behcet's syndrome is briefly reviewed, and fails to provide a uniformly accepted method of treating this rare complication. Intravenous CTX may prove to be another therapeutic option for rapidly progressive glomerulonephritis in the setting of Behcet's syndrome. PMID- 2191234 TI - Senior-Loken syndrome (nephronophthisis and pigmentary retinopathy) associated to liver fibrosis: a family study. AB - We present two sisters with nephronophthisis and pigmentary retinopathy (Senior Loken syndrome) and associated liver fibrosis. Clinical and histological findings are discussed, as well as the importance of family studies. A comparative analysis with previous published cases is made; we found only three other references with this triad. Our report underlines the need to investigate liver disorders in all patients with nephronophthisis and the existence of liver fibrosis as an element of the hereditary 'nephronophthisis complex.' PMID- 2191235 TI - [Cerebral aspergilloma. Review of the literature apropos of a case]. AB - The incidence of mycotic infection of C.N.S. seems to have increased in the last few years and the diagnosis is being made more and more frequently. The authors are reporting a case of a 27 year old man, admitted with severe intracranial hypertension, very poor visual acuity and right motor weakness. The C.T. Scan showed a massive space occupying lesion in the left hemisphere. Only the biopsy, then the surgical removal of the lesion revealed the true histological nature. It turned out to be aspergilloma. The patient expired 13 hours later. Up to date, 25 cases of Aspergillus granulomas have been reported. This disease is included in the entity of neuromycosis. Its specificity compared to the other types of cerebral mycotic localization as for example abscess, meningitis, mycotic aneurysm, lies in the fact that it presents as granulomatous mass in the hemisphere, mimicking a brain tumor without any specific neuroradiological findings. In the light of so far published literature, the authors draw the attention to the fact of the difficulty of diagnosis of this dreadful benign disease due to the lack of specific clinical and radiological findings. They are stressing the necessity of early and vigorous diagnosis mainly in patients with a risk factor to try to reduce the high mortality that has been universally reported in almost all cases. PMID- 2191236 TI - Radiation therapy for arteriovenous malformations: a review. AB - There have been numerous case reports and series of patients treated with partial brain irradiation, linear accelerator-based radiosurgery, gamma knife radiosurgery, and Bragg peak therapy for inoperable arteriovenous malformations (AVMs). These cases are summarized and compared. There is convincing evidence that radiation therapy does have a role in obliterating carefully chosen inoperable lesions. The changes that occur in vessel walls after radiation are reviewed. Data about x-ray and gamma radiation are mostly historical and difficult to evaluate because of the techniques of partial brain irradiation. There is a lack of data about the volume of AVM treated and the minimum dose delivered to the AVM nidus. For gamma knife, heavy particle, and linear accelerator therapy, more complete data are available. The incidence of hemorrhage during the first 2 years after treatment, when radiation-induced vascular changes are proposed to occur, is approximately 2.6% per year for gamma knife therapy, 2% per year for proton beam therapy, 2.3% per year for helium beam therapy, and 2.3% per year for linear accelerator therapy. These rates are similar to the recurrence rate for hemorrhage of 2.2 to 3% per year expected based on the natural history of untreated AVMs. If AVM obliteration after therapy is not achieved, the incidence of recurrent hemorrhage remains between 2% per year after treatment with gamma knife therapy. The incidence of hemorrhage for all patients treated was reported as 0.15% per year in one study and 20% over 8 years in a follow-up study using proton beam therapy. Mortality from hemorrhage after treatment was 0.6% after gamma knife therapy, 2.3% after helium beam therapy, and 2 to 5% after proton beam therapy. These figures for mortality are all lower than the 11% observed for the natural history of untreated AVMs. Permanent neurological deficits experienced as a complication of radiation occurred in 2 to 3% of patients treated with gamma knife therapy, 4% of patients treated with helium beam therapy, 1.7% of patients treated with proton beam therapy, and 3% of patients treated with stereotactic linear accelerator therapy. Proton beam therapy has been used for both small and large lesions. The majority of lesions in patients treated with gamma knife, helium beam, and linear accelerator therapy have been small (usually less than 3.0 cm average diameter) lesions. In these patients with small inoperable lesions treated with accurately directed fields of isocentric radiation, the greatest incidence of AVM obliteration has been observed on follow-up angiograms.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2191237 TI - Radiosurgery for acoustic neurinomas: early experience. AB - We reviewed our early experience with the first 26 patients with acoustic neurinomas (21 unilateral, 5 bilateral) treated by stereotactic radiosurgery using the first North American 201-source cobalt-60 gamma knife. Follow-up ranged from 6 to 19 months (median, 13 months). Serial postoperative imaging showed either a decrease in tumor size (11 patients) or growth arrest (15 patients). Loss of central contrast enhancement was a characteristic change (18 patients). Seven patients had good or serviceable hearing preoperatively. In all 7 the preoperative hearing status was retained immediately after radiosurgery. At follow-up, 3 had preserved hearing, 1 had reduced hearing, and 3 had lost all hearing in the treated ear. Hearing in 1 patient that was nonserviceable preoperatively later improved to a serviceable hearing level. Delayed facial paresis developed in 6 patients, and delayed trigeminal sensory loss developed in 7 patients, none of whom had significant deficits before radiosurgery. Both facial and trigeminal deficits tended to improve within 3 to 6 months of onset with excellent recovery anticipated. Lower cranial nerve dysfunction was not observed. All 26 patients remain at their preoperative employment or functional status. At present, stereotactic radiosurgery is an alternative treatment for acoustic neurinomas in patients who are elderly, have significant concomitant medical problems, have a tumor in their only hearing ear, have bilateral acoustic neurinomas, refuse microsurgical excision, or have recurrent tumor despite surgical resection. Although longer and more extensive follow-up is required, the control of tumor growth and the acceptable rate of complications in this early experience testifies to the future expanding role of this technique in the management of selected acoustic neurinomas. PMID- 2191238 TI - Utilization of unilateral and bilateral stereotactically placed adrenomedullary striatal autografts in parkinsonian humans: rationale, techniques, and observations. AB - A limited clinical pilot study involving an amalgam of specialized disciplines including neurology, neuropharmacology, neuropsychology, neurosurgery, neuroanesthesia, neuroradiology, surgical pathology, neuropathology, and urological surgery was organized to clarify issues related to patient selection, optimization of grafting materials, design of a safe, effective, standardized, and reproducible surgical technique, and possible modification of clinical patterns. After initial assessment of 82 Parkinsonian patients for periods of 6 to 20 months, 10 (age, 39-68 years) were selected for unilateral or bilateral adrenomedullary autografts to the caudate nucleus with ependymal and cerebrospinal fluid contact, employing image-directed stereotactic methods. Selection was made only after clear definition of clinical pattern and optimization of medication responses. Adrenal glands were harvested by a retroperitoneal approach (mean estimated blood loss less than 75 ml). Care was taken to maximize the graft content of medullary tissue. Stereotactic methods afforded standardized, reproducible, precise targeting and transit trajectory with unilateral or bilateral placement of materials within the striatum (tissue volume, 80 mm3) with access to the ventricular fluid of the frontal horn. Considerable variability in satisfactory donor medullary tissue was encountered. One patient did not undergo grafting because of unsatisfactory medullary tissue. No significant surgical complications were noted and all patients were ready for discharge 7 days after surgery. One patient who manifested no apparent clinical change died 6 weeks after bilateral grafting of unrelated causes during a lithotripsy procedure. Postmortem examination disclosed precise graft placement with a paucity of structurally preserved medullary cells. Postoperative observations, including parameters of clinical observation, medication schedules and records, patient and family commentaries, and imaging studies (computed tomograms and single photon emission computed tomograms), have been made for periods from 16 to 20 months. Sustained improvement in preexisting clinical patterns and reduction in drug requirements were observed in 4 of 8 patients. No increased benefit could be ascribed to bilateral graft placement. These observations would indicate a safe, and reproducible surgical method. In addition, the clinical observations indicate favorable alterations in the established pattern of the disorder, which would justify further cautious exploration of alternate donor sources or refinements of biological graft site manipulations. PMID- 2191239 TI - Cytokine gene expression by human gliomas. AB - Two glioma tumor lines and specimens from five patients with gliomas were analyzed to determine genic expression of four growth factors found in human brain. Messenger RNA encoding for interleukin-1 beta, interleukin-6, and basic fibroblast growth factor was found to be expressed in significant amounts in some of these tumors, while mRNA for interleukin-3 was found in small quantities in only the tumor lines. Multiple species of mRNA for basic fibroblast growth factor were found. Expression of growth factor genes may play a role in the growth of human gliomas. PMID- 2191240 TI - Characterization of contractile responses to endothelin in human cerebral arteries: implications for cerebral vasospasm. AB - Cerebral vascular tone is modulated, at least in part, by the vascular endothelium. This probably results from a balance between the release of the endothelium-derived relaxing factor(s) and the endothelium-derived constricting factor(s) (e.g., endothelin). The time course of the induction and the decay of these mutually antagonizing substances differ considerably. Endothelium-derived relaxing factor is probably involved in rapid changes in vascular tone whereas endothelin may be more important in long-term modulation. We have studied the vasoconstrictor properties of endothelin in human cerebral artery strips. Endothelin typically produced an intense, sustained increae in tone over a dose range similar to that seen with other vasoconstrictor substances such as serotonin and prostaglandin F2 alpha (ED50 = 10(-8) M). The response was resistant to selective antagonists of norephinephrine, serotonin, isoproterenol, histamine, acetycholine, and angiotensin II. Only sodium nitroprusside, verapamil, and a disulfide bond reducing agent (dithiothreitol) inhibited the response. The physiological properties of this response are similar to those of a vasoconstrictor protein found in cerebrospinal fluid from patients with cerebral vasospasm after subarachnoid hemorrhage. The time course of the induction of endothelin production is consistent with the temporal sequence of vasospasm, further supporting the hypothesis that endothelin may be involved in this pathological process. PMID- 2191241 TI - Dural arteriovenous fistulas supplied by ethmoidal arteries. AB - Eight patients with dural arteriovenous fistulas (DAVFs) located on the floor of the anterior cranial fossa and supplied by enlarged ethmoidal branches of the ophthalmic artery are described. Five patients showed the classical symptom of intracerebral hemorrhage (all five had ipsilateral frontal lobe hematomas and one also had an associated a subdural hematoma). Two patients exhibited atypical symptoms of proptosis, chemosis, elevated intraocular pressure, and loss of vision secondary to an ethmoidal DAVF, which drained posteriorly to the cavernous sinus. The eighth patient exhibited proptosis and chemosis secondary to a cavernous sinus DAVF and was incidentally found to have an asymptomatic ethmoidal DAVF. One additional patient had two separate dural fistulas: one located on the cribriform plate and the second located in the posterior fossa. Seven of the eight patients were cured by surgical excision of the fistula site; in the remaining patient spontaneous obliteration followed a surgical procedure for a cavernous DAVF. DAVFs involving the floor of the anterior cranial fossa usually present with hemorrhage, but can present with ocular symptoms or be entirely asymptomatic and are effectively treated by surgical excision of the fistula site. PMID- 2191242 TI - Meningioma: a historical study of the tumor and its surgical management. AB - The history of meningioma is reviewed, highlighting the personalities and events that shaped our understanding and management of this tumor. Early descriptions, nomenclature, and the history of surgical removal of meningioma are discussed and the important role of this tumor in the development of neurosurgery as a whole is stressed. PMID- 2191243 TI - Tuberculosis of the skull--a rare condition: case report and review of the literature. AB - A 25-year-old woman exhibited swelling of the scalp and a bony defect of the skull from which Mycobacterium tuberculosis was cultured. The case is reported, and the literature is reviewed. PMID- 2191244 TI - Role of certain hormones with general metabolic action in the expression of sexual differentiation of the rat liver with respect to a special estrogen binding protein. PMID- 2191245 TI - Pathways of peripheral nerve microvascularization and their plasticity (review). PMID- 2191246 TI - Occult spinal dysraphism: neuroradiological study. AB - We present a retrospective study of occult spinal dysraphism in 47 children aged 0 to 14 years, all studied with plain X-rays, 60% with CT and myelo-CT, and 40% with MR. We consider the classification and grading of these malformations, clinical, neuroradiological patterns, and indications for surgery. In the light of our findings and of the published data MR emerges as the key investigation. Only in a few cases of great anatomical complexity is it now necessary to perform CT and myelo-CT as well. A case in point is when the conus and thickened filum terminale are inextricably bound together and can no longer be considered separate structures. We propose the term "neurofibrous structure" to define the conus-thickened-filum-terminale unit when these structure are no longer distinguishable. PMID- 2191247 TI - Wyburn-Mason syndrome. A case report and review of the literature. AB - Wyburn-Mason syndrome is a neurocutaneous disorder which typically presents with unilateral vascular abnormalities involving the facial structures, orbits and brain. We would like to present the clinical and radiological features in a newborn who had bilateral manifestations of this disorder and review the literature. PMID- 2191248 TI - Ultrastructural differences between smooth and thorny gonadotropin-releasing hormone neurons. AB - It has been suggested that gonadotropin-releasing hormone neurons with irregular contours receive more synaptic input than do those with smooth contours. To test this hypothesis, a morphometric analysis of gonadotropin-releasing hormone neurons of differing shapes was made. Male Sprague-Dawley rats were perfused and 40-microns tissue sections from the preoptic area were treated for the demonstration of gonadotropin-releasing hormone immunoreactivity, using the avidin-biotin horseradish peroxidase method with 3,3'-diaminobenzidine as the chromogen. Gonadotropin-releasing hormone neurons with either a smooth or a highly irregular outline, sampled at three depths ultrastructurally, were compared for density of synaptic innervation and for relative content of various subcellular organelles. Point counting stereology comparisons of five gonadotropin-releasing hormone neurons of the two shapes in four rats revealed that smooth neurons contained less cytoplasm than "thorny" neurons, but the size of their nuclei was the same. There were more and larger nucleoli in smooth cells. Thorny neurons contained more Golgi apparatus and more mitochondria, but the amount of rough endoplasmic reticulum was the same in neurons of the two morphological types. There was no difference in the incidence of synapses or in the density of synaptic input as measured per unit of neuronal membrane in smooth and thorny gonadotropin-releasing hormone neurons. These results suggest that smooth-contoured gonadotropin-releasing hormone neurons may be more actively transcribing a message while thorny neurons are more actively engaged in peptide processing and packaging.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2191249 TI - Ode to Koop. PMID- 2191250 TI - Long odyssey of babesiosis. AB - The history of babesiosis is traced from the discovery of the parasite in 1888, to its present endemic niche. The author uncovers clinical and epidemiological features of human babesiosis in a patient hospitalized in New Jersey. PMID- 2191251 TI - Hazards smokers impose. AB - Tobacco smoke is the single most important source of exposure for the nonsmoking population to harmful air pollution. Uptake, biological reaction, and associated pathology document the potential for serious health consequences, raise ethical and legal questions, and demand comprehensive legislative action. PMID- 2191252 TI - Idiopathic chronic fatigue. A primary disorder. AB - Idiopathic chronic fatigue, an entity worthy of attention, understanding, and treatment, has disappeared from medical and psychiatric publications. Nonetheless, it is an important clinical phenomenon. PMID- 2191253 TI - Insulin-degrading activity and insulinase-inhibiting activity in acute leukemia. AB - Insulin-degrading and insulinase-inhibiting activity of whole blood and erythrocytes of 146 children affected with acute leucosis of different stages were investigated. No statistically reliable difference between the data of insulin-degrading activity in acute leucosis and healthy children was found. Insulinase-inhibiting activity of both the hemolysate of blood and erythrocytes was increased in children in the active stage of the disease. PMID- 2191254 TI - [The differential diagnosis and the problems of treating constitutional tall growth in girls]. AB - This paper gives a review of the literature about diagnostic and therapy in constitutionally tall girls (differential diagnosis, estimation of bone age, height prediction, height reduction). PMID- 2191255 TI - [The therapy of tall stature in girls--a review]. PMID- 2191256 TI - [The effect of insulin on lethality in mice with acute ethanol poisoning]. AB - Intraperitoneal injection of 25% ethanol solution in LD80 doses caused death of approximately 60% of satiated and starving animals in the first 60 minutes. The death peak was encountered 3-10 minutes after the injection of ethanol and corresponded with the peak of its concentration in the blood. The early death of the animals was connected with arrest of respiration in inhibition of cardiac activity. A tendency towards increase of ethanol LD50 60 minutes after its injection in administration of insulin was encountered. The changes of ethanol LD50 were statistically insignificant. PMID- 2191258 TI - Pathogenesis and prevention of neonatal chronic lung disease: recent developments. PMID- 2191257 TI - [The coagulability of the blood and lymph under normal and pathological conditions]. PMID- 2191259 TI - Drug therapy for bronchopulmonary dysplasia. AB - With improved survival of critically ill premature infants, BPD has become an important sequela of neonatal intensive care. A variety of medications are used in the management of BPD. In this article we have attempted to summarize clinical efficacy, pharmacokinetics, and side effects of many of these medications. Longer term studies on the efficacy of drug therapy are needed and may be facilitated by the development of accurate and reproducible computerized techniques for the measurement of pulmonary mechanics in neonates. Ultimately, new pharmacologic agents or other strategies that will prevent lung injury from hyperoxia and mechanical ventilation or accelerate tissue repair once injury occurs will play a major role in the prevention and treatment of infants with BPD. PMID- 2191260 TI - Lithium, clinical research, and cystic fibrosis. PMID- 2191261 TI - Relationship between infant lung mechanics and childhood lung function in children of very low birthweight. AB - Twenty-seven children of very low birthweight (less than or equal to 1,500 g) whose lung function had been measured on several occasions during the first year were studied at the age of about 9 years. Fifteen of the children had received neonatal intermittent positive pressure ventilation, mostly for respiratory distress syndrome. Ten of the ventilated children were still oxygen dependent at 30 days of age. Compared to the remainder of the group, mechanically ventilated children had reduced lung compliance in early infancy and increased thoracic gas volume in the middle of their first year. These changes correlated with the level of neonatal respiratory therapy as indicated by the oxygen score. Lung compliance in early infancy, but not thoracic gas volume, correlated with forced expiratory volume at 1 second recorded at 9 years. On the other hand, reduced airway conductance showed no significant correlation with the neonatal oxygen score, but there was a strong correlation between airway conductance late in infancy and lung function at 9 years. This relationship was independent of neonatal mechanical ventilation. We conclude that perinatal factors, which may be associated with disturbed lung mechanics early in infancy, are only weak and indirect predictors of childhood lung function. Airway conductance late in infancy, determined by constitutional factors, prematurity itself or other undetermined factors, is a good predictor of airway function at 9 years. PMID- 2191262 TI - Titration of continuous positive airway pressure by the pattern of breathing: analysis of flow-volume-time relationships by a noninvasive computerized system. AB - Infants can defend or even dynamically elevate their functional residual capacity with additional respiratory muscle work by retarding early expiratory airflow (V) with postinspiration inspiratory muscle activity and/or laryngeal narrowing, or by starting inspiration before expiration to the relaxation volume has been completed. In order to study the effect of continuous positive airway pressure (CPAP) on both phenomena in 23 infants (birthweight 1,746 +/- 417 g), we elevated the airway pressure stepwise in 0.2 kPa increments. A computerized bedside flow volume (V/V) analysis was used for evaluation. In 16 "responders" early expiration braking decreased and "premature inspiratory interruption" was postponed at an "appropriate CPAP level." The linear segment (relaxation line) of the V/V-loop was lengthened until expiratory time reached a maximum. Elevation of CPAP beyond this level again produced a rapid, shallow pattern, often combined with flow acceleration late in expiration (recruitment of expiratory muscles). In the remaining seven infants (non-responders) these latter signs of excessive airway pressure already occurred at the lowest CPAP levels applied during the "titration trials." Respiratory rate without CPAP was different between responders (84 +/- 17/min) and non-responders (46 +/- 17/min). This approach for determining the appropriate CPAP level might reduce the risk of respiratory muscle fatigue. PMID- 2191263 TI - Hyaline membrane disease in the newborn: diagnosis by ultrasound. AB - The authors report a new method of diagnosing hyaline membrane disease (HMD) in newborns: ultrasound. Babies with HMD display a specific pattern with retrohepatic hyperechogenicity on abdominal ultrasound. The specificity of the pattern was verified in 40 prematures with respiratory distress syndrome. The sign was present in 24, and in 22 of these the final diagnosis was moderate or marked HMD. In the last 2, mild HMD was suggested. The pattern was absent in the 16 others, none of whom had HMD. The pattern probably results from an ultrasound artifact: summation of multiple aerated airways surrounded by collapsed alveoli. Follow-up examinations were possible in 13 babies with HMD. Hyperechogenicity disappeared in 8 of these patients within 6-9 days and in 3 within 10-20 days; it persisted for 60 and 70 days in 2 with bronchopulmonary dysplasia. In conclusion, retrohepatic hyperechogenicity in newborns is pathognomonic for HMD and allows an instant diagnosis. The persistence of the pattern could be a useful criterion for evaluation of the prognosis. PMID- 2191264 TI - Calcified neonatal renal vein thrombosis demonstration by CT and US. AB - Two cases of calcified renal vein thrombosis (RVT) were diagnosed, incidentally, within the first weeks of life. The CT images present the virtually diagnostic branching pattern of calcification that has been previously noted on pathology specimen radiographs. The CT and US images show peripheral renal vein, central renal vein and inferior vena cava calcification conforming to the two theoretical origins of intravascular calcification. The patients had normal laboratory results and no symptoms related to renal vein or inferior vena cava thrombi. PMID- 2191265 TI - Sonographic findings of adrenal cortical carcinomas in children. AB - Fourteen children with adrenal cortical carcinoma were evaluated by ultrasonography. The neoplasms, 2.5 cm-19 cm in maximum diameter, were all well circumscribed. The four smaller lesions were either homogeneously hypoechoic (2 patients) or generally hyperechoic (2 patients). In the 10 patients with larger tumors, a complex predominantly echogenic pattern was demonstrated, eight of which contained radiating linear echoes, the "scar sign". This finding, although not specific, when present in a large adrenal mass, is suggestive of a cortical carcinoma. Associated findings of vascular invasion or retroperitoneal adenopathy supported the diagnosis of a malignant adrenal neoplasm in 3 patients. PMID- 2191266 TI - Adrenocortical carcinoma with extension into inferior vena cava and right atrium: report of 3 cases in children. AB - We present three cases of adrenocortical carcinoma, a rare tumor in children, with extension into the inferior vena cava and the right atrium. The diagnosis is facilitated by use of ultrasonography, computed tomography and magnetic resonance imaging. PMID- 2191267 TI - Massive florid reactive periostitis. AB - Florid reactive periostitis is a rare, benign process usually occurring in the small, tubular bones of the hands and feet. Typically the lesion occurs in an adolescent or young adult and presents as a small area of pain and erythema over the affected bone. Although the histologic features may suggest malignancy, there is usually little radiographic evidence to support such a diagnosis. In the following report an unusual example of this entity is described whose large size and relentless local progression led to initial diagnostic uncertainty and eventual aggressive management. This case suggests that a wide spectrum of radiologic and morphologic changes may be seen in this entity and that a seemingly unrelated genetic disease may alter the typical clinical course. PMID- 2191268 TI - Multiseptate gallbladder in a child: incidental diagnosis on sonography. PMID- 2191269 TI - Aortic thrombosis in a neonate with undetectable protein C. PMID- 2191270 TI - Atypical leiomyoma arising in an hepatic vein with extension into the inferior vena cava and right atrium. Report of a case in a child. AB - We report an atypical leiomyoma arising in an hepatic vein and extending into the inferior vena cava and right atrium in a fourteen year old boy. US, CT and MRI facilitated diagnosis and removal of this tumor. PMID- 2191271 TI - Global progress in the control of diarrheal diseases. PMID- 2191272 TI - Varicella myocarditis. PMID- 2191274 TI - [40 years at the Pulmonary Disease Treatment Center for Children in Karpacz]. AB - The history of the Childrens Pneumonologic Center in Karpacz is presented. Development of the center is shown, profile of therapy, and diagnostical methods. PMID- 2191273 TI - Transfection of activated ras into an excitable cell line (AtT-20) alters tetrodotoxin sensitivity of voltage-dependent sodium current. AB - The sensitivity of voltage-dependent sodium current to the sodium channel blocker tetrodotoxin (TTX) is altered by transfection of a c-Ha-ras oncogene into an excitable cell line. Control AtT-20 cells, a cell line derived from a mouse anterior pituitary tumor, were found to express both a TTX-sensitive and a TTX resistant sodium current. AtT-20 cells transfected with the c-Ha-ras gene expressed only a TTX-sensitive current. Properties of TTX-sensitive and resistant currents were also examined. No differences in voltage dependence of activation or inactivation between the TTX-sensitive and -resistant currents were observed. The rate of inactivation of the TTX-resistant current in control cells was slower, than that of the TTX-sensitive current in either control or ras transfected AtT-20 cells. PMID- 2191275 TI - [Etiological factors in secondary bacterial infections from the authors' own clinical material]. AB - An analysis of etiological factors of secondary bacterial infections was carried out in 64 patients with pneumonias. In most of the patients gram negative rods were cultured. Most often the pneumonias were caused by Klebsiella pneumoniae and Escherichia coli. A single causative agent was found in the majority of the patients (60.7%), less frequently two, least three. PMID- 2191276 TI - [Sino-bronchial syndrome]. PMID- 2191277 TI - [Sleep apnea syndrome]. PMID- 2191278 TI - The dichotomy of drugs and psychotherapy. AB - Psychiatrists increasingly combine medication with psychotherapy when treating depression and other disorders. Among the public and practitioners, however, there remains controversy about the compatibility of these treatments. The roots of the controversy can be traced to the ubiquity of dualistic beliefs about mind and body and the historical development of mental health professions. Confusion has also been generated by deriving notions of etiology from observations of phenomenology and treatment response. Understanding these issues will help the practitioner to more successfully combine treatment modalities when both are indicated. PMID- 2191279 TI - The psychotherapy of mania. AB - The manic or hypomanic patient paradoxically lives on the edge of loss and lowered self-esteem. This is due to present realities of the impact of the illness upon life and the prospect of cycling into depression and earlier developmental problems to which bipolar patients may be especially prone. Furthermore, manic behavior itself engages others in arguments and countertransference problems that may actually worsen the course of the illness. A psychotherapeutic approach taking these factors into account can have a favorable impact on the acute episode and the long-term course of the illness, provided the patient and psychiatrist are able to form a trusting relationship that survives any recurrences. Justification for these views derives from small series of patients and anecdotal impressions of experienced clinicians. Empirical research is needed on the efficacy of psychotherapy, independent of medication effects. PMID- 2191280 TI - Integrating psychopharmacotherapy, psychotherapy, and mental structure in the treatment of patients with personality disorders and depression. AB - Thus, we see that dynamically and phenomenologically, overlaps and seeming integrations exist between biologic illness and psychologic illness, between depression and personality disorders, between medication and psychotherapy, and between reparative therapy and reconstructive therapy. These relationships, for now, are best studied in the clinical laboratory of combined treatment. Full systematic descriptions and causal relationships are in the process of emerging. For this work, specific structural descriptions will be needed of depression and other Axis I illnesses apart from, and as they interact with, the structure of personality defenses. PMID- 2191281 TI - Treatment of borderline patients: a pragmatic approach. AB - Outlined in the preceding sections are what one could call the ABCDs of treating borderline patients. A = analytically informed psychotherapy; B = behavior therapy; C = cognitive therapy; and D = drug therapy. Together they add up to "E": eclectic therapy. In this pragmatic approach, the therapist will assess at the outset (1) amenability to exploratory therapy, but also (2) the need for supportive measures, including education, rehabilitation, and expansion of outside interests, (3) indications for behavioral technics (socially alienating habits, handwashing compulsions, phobias), (4) indications for cognitive measures (conflicts or fears resolvable through rational explanation or logical weighing of alternatives), and (5) indications for pharmacotherapy. All these steps involve the careful weighing of biologic/constitutional, psychodynamic, and, where present, posttraumatic factors, as well as personality assets and habitual problem-solving style. This will help assure against overreliance on a technic that does not fit with the patient's personality and against unwise persistence in a technic that is uncongenial or threatening. Patients already in stable life situations who are seeking help because of life crises may respond well to a brief course of therapy. Borderlines in late adolescence or early adult life, if self-destructive and not yet able to form lasting relationships (or to live contentedly without them), usually require sustained treatment over several years, preferably with the same therapist. Appropriate selection of medications, where indicated, should reduce impulsivity, aggressivity, and psychoticism. This, in turn, will facilitate psychotherapeutic work on maladaptive interpersonal patterns, exaggerated "all-or-none" responses to relatively innocuous stimuli, overpersonalized responses to other people's remarks, and so on. Therapists trained in identical methods will evaluate the same patient in somewhat different ways owing to their differences in personality and perception. This may lead to different sets of priorities and suggests different tactics that are still within the realm of therapeutic efficacy. Those trained primarily in one of the "ABCDs" may have equal success, yet via a different route than the one taken by therapists of a different subspecialty. Borderline patients, perhaps two out of five, often drop out of treatment no matter who the therapist. Yet two out of three patients, if followed long enough, eventually have a good result. One therapist's failure will be his colleague's success, and vice versa. Therapists, to maximize the success of their own efforts, need to be sufficiently steeped in at least one theoretical model of psychopathology/psychotherapy so as not to feel "lost" when confronted by the often bewildering dynamics and symptoms of their borderline patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2191282 TI - Nonphysician psychotherapist-physician pharmacotherapist: a new model for concurrent treatment. AB - In the last century the mental health field has vacillated between a biologic versus a psychologic model of the mind. Only in the last two decades have proponents of both views calmly discussed their virtues and limitations. As a result, clinicians have begun to promulgate the concept of an integrated, concurrent psychotherapy and pharmacotherapy. While this debate has raged in the psychiatric field there has been a parallel proliferation of nonphysician mental health professionals. Most of these mental health clinicians come from training programs steeped in the traditions of a psychodynamically based treatment that occurs within the interpersonal context. Today more and more of these clinicians compete for the increasing population of those seeking relief. The result of these two movements has been the introduction of a unique form of treatment in which a patient sees two therapists. In this triangular treatment, the pharmacotherapist prescribes medications and the psychotherapist provides the interpersonal therapy. In order for all practitioners to participate in this form of triadic treatment they must appraise themselves of not only the historical debates preceding this therapeutic concordance but of the transference and countertransference potentials. Some patients can have idealizing, magical, and nurturing transferences toward either therapist in the triangular relationship. Other patients can be narcissitically wounded, with a negative devaluing response toward either therapist. Paralleling the patient's transference distortions are the therapists' countertransference reactions. These can run from the omnipotent identification with the patient's idealization to the devalued, distancing response toward oneself or the patient. If these distortions are not checked they can intrude on the treatment, acting out the patient's internal split self-object representations and ultimately sabotaging treatment. Successful attention to transference and countertransference phenomena can lead to an enhanced treatment in which the biologic and psychologic treatments have a synergistic effect. Only then will we be capable of fully evaluating and researching the positive and negative effects of combined psychotherapy and pharmacotherapy with two different therapists. The outgrowth of this research will be improved patient care by enhancing our capacity to identify those patients and therapists who are good candidates for this triangular treatment relationship. PMID- 2191283 TI - The anterior cruciate ligament. AB - Our knowledge of the anterior cruciate ligament has expanded rapidly over the last decade. Recent advances in arthroscopic techniques, the development and release of synthetic stents and prostheses, increasing laboratory and clinical data involving allograft implantation, and biomechanical research in knee rehabilitation have led to a bewildering array of choices for treatment of anterior cruciate ligament deficiency. As new information and techniques are presented, and new synthetic and biological materials become available, orthopedic surgeons must judge their value and modify treatment recommendations accordingly. A thorough knowledge of the basic science and clinical information is necessary to appropriately evaluate these new advances. A review of our current knowledge of the anterior cruciate ligament is presented to facilitate this evaluation process. PMID- 2191284 TI - Posterior augmentation during closure following total hip arthroplasty. PMID- 2191285 TI - [Social interaction with autistic children: an approach to disorder-specific, therapy-oriented diagnosis]. AB - Assessment and intervention is a great challenge in working with autistic children. The problems of assessment can be described as a function of the autism specific developmental problem of decontextualization. The problems of psychological intervention as a related problem of generalization. To control both problems in the social interaction with autistic children one is called to create and videotape situations of social interaction. One can create units of observation on the basis of development psychology studies. Those units are derived from the three main aspects of social interaction, the interactional situation, the interactional style and the interaction behavior. The audio visuell taping and videoanalysis of many such interactions-sequences at the beginning, in the course and at the end of the intervention process make it possible to control the problems of intervention planning, finetuning and effectiveness. PMID- 2191286 TI - [Some findings in infant observation and the new developmental psychology]. AB - In psychoanalytic nosology certain disorders, especially the so-called "early pathologies" or "preoedipal disorders", are labeled in terms of traditional psychoanalytic developmental psychology. The implications of this terminology served as a starting point for the development of special psychotherapeutic approaches, which are modifications of the psychoanalytical standard technique. In the light of the results of infant observation and of recent developmental psychology some of the concepts of psychoanalytic developmental psychology need to be revised, especially those of "normal autism", the "undifferentiated selfobject matrix" and the assumptions concerning the relationship between primary process and secondary process. PMID- 2191287 TI - A cytochemical study of the serotoninergic, cholinergic and peptidergic components of the reproductive system in the monogenean parasite, Diclidophora merlangi. AB - The reproductive system of the monogenean gill parasite, Diclidophora merlangi, was examined for the presence of cholinergic, serotoninergic and peptidergic innervation using cytochemical and immunocytochemical techniques. Cholinesterase activity and 5-hydroxytryptamine immunoreactivity (5-HT-IR) were confined to neural elements of the male reproductive system, being evident in the innervation of the cirrus, whereas only 5-HT was present in nerves and somata of the elongate seminal vesicle. Peptidergic innervation was localised to both the male and female reproductive systems of the worm. Within the female reproductive apparatus pancreatic polypeptide, peptide tyrosine tyrosine, neuropeptide Y, substance P, neurokinin A, eledoisin, FMRFamide and gastrin/cholecystokinin immunoreactive fibres and somata were observed in the oviduct, vitelline reservoir and ovovitelline duct. Intense peptide immunoreactivity was identified in fibres in the wall of the ootype and in a surrounding population (greater than 100) of somata that were situated beyond Mehlis' gland cells and all of which were connected to the ootype wall by fine cytoplasmic connectives. The strategic location of this peptidergic cell population infers its involvement in the egg forming sequence in this platyhelminth parasite. PMID- 2191288 TI - IgG response of rats to the excretory-secretory products of Litomosoides carinii. AB - The nature of antibody responses to the excretory-secretory (ES) products of adult worms and microfilariae (Mf) of Litomosoides carinii in albino rats and their possible role in protection have been studied. Rats were immunized with ES products derived from in vitro incubation of adults or Mf. The sera from these rats promoted neutrophil-mediated killing of Mf in vitro. The antibody responsible for the cytocidal activity was identified as IgG isotype. Indirect fluorescent antibody test showed the presence of IgG on the surface of Mf incubated in either of the immune sera. The immune sera were effective in clearing the circulating Mf in Mastomys natalensis, indicating the protective nature of the antibody. Thus, L. carinii in culture liberate functional antigens that seem to have protective potential. PMID- 2191289 TI - Passive immunization against Plasmodium chabaudi malaria with Pch 21 merozoite monoclonal antibody. PMID- 2191290 TI - Refolding of Escherichia coli dihydrofolate reductase: sequential formation of substrate binding sites. AB - The kinetics of refolding of Escherichia coli dihydrofolate reductase (EC 1.5.1.3) have been examined upon dilution of unfolded enzyme in 4.5 M urea to 1.29 M urea in 0.02 M phosphate buffer (pH 7.2) at 10 degrees C. Changes in the intrinsic protein fluorescence on refolding are characterized by four phases. Based on changes in the amplitudes of these phases, as a consequence of quenching of the intrinsic fluorescence by ligands, it is possible to determine the step at which a ligand binds during the refolding process. The results show that either NADP or NADPH binds to the last species formed in a sequence involving three intermediates between the unfolded and native states. Dihydrofolate, on the other hand, binds during the formation of the second observed intermediate. When refolding is performed in the presence of methotrexate, an analogue of dihydrofolate, and NADPH, NADPH binds, as determined from changes in NADPH fluorescence, to the third observed intermediate rather than the last (fourth) species formed. Measurements of the recovery of enzymatic activity during refolding suggest that dihydrofolate also induces NADPH binding prior to the final observed folding phase. These results define more closely the formation of structural domains during the folding of dihydrofolate reductase. PMID- 2191291 TI - Proofreading in vivo: editing of homocysteine by methionyl-tRNA synthetase in Escherichia coli. AB - Previous in vitro studies have established a pre-transfer proofreading mechanism for editing of homocysteine by bacterial methionyl-, isoleucyl-, and valyl-tRNA synthetases. The unusual feature of the editing is the formation of a distinct compound, homocysteine thiolactone. Now, two-dimensional TLC analysis of 35S labeled amino acids extracted from cultures of the bacterium Escherichia coli reveals that the thiolactone is also synthesized in vivo. In E. coli, the thiolactone is made from homocysteine in a reaction catalyzed by methionyl-tRNA synthetase. One molecule of homocysteine is edited as thiolactone per 109 molecules of methionine incorporated into protein in vivo. These results not only directly demonstrate that the adenylate proofreading pathway for rejection of misactivated homocysteine operates in vivo in E. coli but, in general, establish the importance of error-editing mechanisms in living cells. PMID- 2191292 TI - Imaging of DNA sequences with chemiluminescence. AB - We have coupled a chemiluminescent detection method that uses an alkaline phosphatase label to the genomic DNA sequencing protocol of Church and Gilbert [Church, G. M. & Gilbert, W. (1984) Proc. Natl. Acad. Sci. USA 81, 1991-1995]. Images of sequence ladders are obtained on x-ray film with exposure times of less than 30 min, as compared to 40 h required for a similar exposure with a 32P labeled oligomer. Chemically cleaved DNA from a sequencing gel is transferred to a nylon membrane, and specific sequence ladders are selected by hybridization to DNA oligonucleotides labeled with alkaline phosphatase or with biotin, leading directly or indirectly to deposition of enzyme. If a biotinylated probe is used, an incubation with avidin-alkaline phosphatase conjugate follows. The membrane is soaked in the chemiluminescent substrate (AMPPD) and is exposed to film. Dephosphorylation of AMPPD leads in a two-step pathway to a highly localized emission of visible light. The demonstrated shorter exposure times may improve the efficiency of a serial reprobing strategy such as the multiplex sequencing approach of Church and Kieffer-Higgins [Church, G. M. & Kieffer-Higgins, S. (1988) Science 240, 185-188]. PMID- 2191293 TI - Sequence and structural similarities between the leucine-specific binding protein and leucyl-tRNA synthetase of Escherichia coli. AB - A role for the leucyl-tRNA synthetase (EC 6.1.1.4) has been established for regulating the transport of leucine across the inner membrane of Escherichia coli by the leucine, isoleucine, valine (LIV-I) transport system. This transport system is mediated by interactions of periplasmic binding proteins with a complex of membrane-associated proteins, and transcription of the high-affinity branched chain amino acid transport system genes is repressed by growth of E. coli on high levels of leucine. We now report results from sequence comparisons and structural modeling studies, which indicate that the leucine-specific binding protein, one of the periplasmic components of the LIV-I transport system, contains a 121 residue stretch, representing 36% of the mature protein, which displays both sequence and structural similarities to a region within the putative nucleotide binding domain of leucyl-tRNA synthetase. Early fusion events between ancestral genes for the leucine-specific binding protein and leucyl-tRNA synthetase could account for the similarity and suggest that processes of aminoacylation and transport for leucine in E. coli may be performed by evolutionarily interrelated proteins. PMID- 2191294 TI - Trans-activating rev protein of the human immunodeficiency virus 1 interacts directly and specifically with its target RNA. AB - The 20-kDa phosphorylated rev protein from human immunodeficiency virus 1 has been shown to transactivate posttranscriptionally the expression of viral structural proteins by selective stabilization and nuclear export of unspliced and incompletely spliced viral mRNA. We could demonstrate in gel-mobility and immunoprecipitation assays that the recombinant rev protein purified from a baculovirus expression system forms a distinct and specific complex with its target RNA (rev-responsive element), a 234-nucleotide sequence within the envelope coding region of human immunodeficiency virus 1. No complex formation could be observed using RNAs with similar secondary structure nor with other human immunodeficiency virus 1 recombinant proteins. Deletion analysis mapped this specific binding to the first 90 nucleotides of this rev-responsive element, which contains a U2 small nuclear RNA homologous region. We propose that the specific binding of rev to its target RNA sequence plays an essential part in releasing an incompletely spliced viral mRNA containing this target sequence to the cytoplasm. PMID- 2191295 TI - Enhancement of bone marrow allografts from nude mice into mismatched recipients by T cells void of graft-versus-host activity. AB - Transplantation of 8 x 10(6) C57BL/6-Nu+/Nu+ (nude) bone marrow cells into C3H/HeJ recipients after conditioning with 8 Gy of total body irradiation has resulted in a markedly higher rate of graft rejection or graft failure compared to that found in recipients of normal C57BL/6 or C57BL/6-Bg+/Bg+ (beige) T-cell depleted bone marrow. Mixing experiments using different numbers of nude bone marrow cells with or without mature thymocytes (unagglutinated by peanut agglutinin) revealed that engraftment of allogeneic T-cell-depleted bone marrow is T-cell dependent. To ensure engraftment, a large inoculum of nude bone marrow must be supplemented with a trace number of donor T cells, whereas a small bone marrow dose from nude donors requires a much larger number of T cells for engraftment. Marked enhancement of donor type chimerism was also found when F1 thymocytes were added to nude bone marrow cells, indicating that the enhancement of bone marrow engraftment by T cells is not only mediated by alloreactivity against residual host cells but may rather be generated by growth factors, the release of which may require specific interactions between T cells and stem cells or between T cells and bone marrow stroma cells. PMID- 2191296 TI - The highly conserved amino acid sequence motif Tyr-Gly-Asp-Thr-Asp-Ser in alpha like DNA polymerases is required by phage phi 29 DNA polymerase for protein primed initiation and polymerization. AB - The alpha-like DNA polymerases from bacteriophage phi 29 and other viruses, prokaryotes and eukaryotes contain an amino acid consensus sequence that has been proposed to form part of the dNTP binding site. We have used site-directed mutants to study five of the six highly conserved consecutive amino acids corresponding to the most conserved C-terminal segment (Tyr-Gly-Asp-Thr-Asp-Ser). Our results indicate that in phi 29 DNA polymerase this consensus sequence, although irrelevant for the 3'----5' exonuclease activity, is essential for initiation and elongation. Based on these results and on its homology with known or putative metal-binding amino acid sequences, we propose that in phi 29 DNA polymerase the Tyr-Gly-Asp-Thr-Asp-Ser consensus motif is part of the dNTP binding site, involved in the synthetic activities of the polymerase (i.e., initiation and polymerization), and that it is involved particularly in the metal binding associated with the dNTP site. PMID- 2191297 TI - Characterization of the fusion domain of the human immunodeficiency virus type 1 envelope glycoprotein gp41. AB - The human immunodeficiency virus transmembrane glycoprotein gp41 has at its amino terminus a strongly hydrophobic stretch of 28 amino acids flanked by a highly conserved series of polar amino acids. To investigate the role in syncytium formation of the hydrophobic amino terminus of gp41 and the polar border of this hydrophobic region, we introduced eight single-amino acid substitutions and one double-amino acid substitution in the amino-terminal 31 amino acids of gp41. The mutant envelope glycoproteins were expressed from two distinct human immunodeficiency virus type 1 envelope glycoprotein expression vectors; the effects of the mutations on syncytium formation, envelope glycoprotein transport, secretion, and CD4 receptor-binding were analyzed. Results showed that polar substitutions throughout the hydrophobic amino terminus of gp41 greatly reduced or blocked syncytium formation mediated by the human immunodeficiency virus type 1 envelope glycoproteins, as did nonconservative mutations in the polar border of the hydrophobic amino terminus. Mutations at gp41 amino acids 15, 26, and 29 also significantly increased the extent of gp120 secretion into the extracellular medium. None of the mutations detectably affected envelope glycoprotein processing or envelope glycoprotein binding to CD4. PMID- 2191298 TI - A DNA replication enhancer in Saccharomyces cerevisiae. AB - We have dissected the autonomously replicating sequence ARS121 using site directed in vitro mutagenesis. Three domains important for origin function were identified; one of these is essential and contains an 11-base-pair sequence resembling the canonical ARS core consensus; the second region, deletion of which affects the efficiency of the origin, is located 3' to the T-rich strand of the essential sequence and encompasses several elements with near matches to the ARS core consensus; the third region, containing two OBF1 DNA-binding sites and located 5' to the essential sequence, also affects the efficiency of the ARS. Here we demonstrate that a synthetic OBF1 DNA-binding site can substitute for the entire third domain in origin function. A dimer of the synthetic binding site, fused to a truncated origin containing only domains one and two, restored the origin activity to the levels of the wild-type ARS. The stimulation of origin function by the synthetic binding site was relatively orientation independent and could occur at distances as far as 1 kilobase upstream to the essential domain. Based on these results we conclude that the OBF1 DNA-binding site is an enhancer of DNA replication. We suggest that the DNA-binding site and the OBF1 protein are involved in the regulation of the activation of nuclear origins of replication in Saccharomyces cerevisiae. PMID- 2191299 TI - Endothelins are more sensitive than sarafotoxins to neutral endopeptidase: possible physiological significance. AB - Incubation of endothelins (ETs) with bovine kidney neutral endopeptidase (NEP) resulted in a selective two-step degradation with loss of biochemical activity. The Km of the enzyme indicated high-affinity binding, and hydrolysis was completely inhibited by phosphoramidon. The first step was nicking of the Ser5 Leu6 bond, followed by cleavage at the amino side of Ile19. The nicked peptide exhibited biochemical activities comparable to those of the intact peptide--i.e., binding to the ET receptor, induction of inositol phospholipid hydrolysis, and toxicity. The twice-cleaved product was inactive. The sarafotoxins (SRTXs) were more resistant than the ETs to NEP: for example, the half-time for ET-1 was approximately 1 hr, while it was approximately 4 hr for SRTX-b and even higher for SRTX-c. These in vitro findings may indicate a regulatory role of NEP (or similar enzymes) in the physiological inactivation of ETs. They might also help to explain why under certain physiological conditions ETs may be less toxic than SRTXs. PMID- 2191300 TI - Interaction of an NF-kappa B-like factor with a site upstream of the c-myc promoter. AB - The c-myc protooncogene has been implicated in control of growth and differentiation of mammalian cells. For instance, growth arrest is often preceded by reduction in c-myc mRNA and gene transcription. To elucidate the mechanisms of control of c-myc gene transcription, we have begun to characterize the interaction of nuclear factors with the 719-base-pair (bp) c-myc regulatory domain, located 1139-421 bp upstream of the P1 start site of the mouse gene. Nuclear extracts from exponentially growing WEHI 231 murine B-lymphoma cells formed multiple complexes in mobility-shift assays. Changes in complex distribution were observed in growth-arrested WEHI 231 cells, and a major site of this interaction mapped to a 21-bp sequence that is similar to the sequences recognized by the NF-kappa B family of proteins. Binding of NF-kappa B-like factors was demonstrated by oligonucleotide competition. Induction of complex formation upon 70Z/3 pre-B- to B-cell differentiation, enhancement of binding by GTP, and detergent-induced release of inhibitor protein suggested that NF-kappa B itself is one member of the family that can bind. Transfection of thymidine kinase-chloramphenicol acetyltransferase constructs containing the 21-bp c-myc sequence into Jurkat cells demonstrated increased chloramphenicol acetyltransferase activity upon phorbol ester and phytohemagglutinin treatment. These results suggest the involvement of NF-kappa B-like factors in the regulation of c-myc transcription. PMID- 2191301 TI - Cooperative interactions between transcription factors Sp1 and OTF-1. AB - We have examined whether the functional synergism between transcription factors Sp1 and OTF-1 involves cooperativity in binding. To demonstrate cooperativity, synthetic enhancers were constructed in which Sp1-binding sites were combined with various OTF-1-binding sites that differed in their binding affinities. The ability of these constructions to activate transcription from the human U2 small nuclear RNA promoter was measured. The results showed that an Sp1-binding site stimulated transcription 2-fold when combined with a high-affinity binding site for OTF-1. When combined with a low-affinity OTF-1-binding site, in contrast, a 20-fold stimulation of transcription was observed. The stimulatory effect of Sp1 was moreover influenced by the distance between the Sp1- and OTF-1-binding sites and the functional cooperation was mirrored by the cooperative formation of OTF-1 and Sp1-specific protein-DNA complexes in vitro. We conclude from these results that the functional cooperation between OTF-1 and Sp1 involves physical interactions between the two transcription factors resulting in cooperative binding. The results thus reveal a mechanism by which Sp1 can modulate transcription. PMID- 2191302 TI - Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse. AB - Osteopetrotic (op/op) mutant mice suffer from congenital osteopetrosis due to a severe deficiency of osteoclasts. Furthermore, the total number of mononuclear phagocytes is extremely low in affected mice. Serum, 11 tissues, and different cell and organ conditioned media from op/op mice were shown to be devoid of biologically active colony-stimulating factor 1 (CSF-1), whereas all of these preparations from littermate control +/+ and +/op mice contained the growth factor. The deficiency was specific for CSF-1 in that serum or conditioned media from op/op mice possessed elevated levels of at least three other macrophage growth factors. Partial correction of the op/op defect was observed following intraperitoneal implantation of diffusion chambers containing L929 cells, which in culture produce CSF-1 as their sole macrophage growth factor. No rearrangement of the CSF-1 gene in op/op mice was detected by Southern analysis. However, in contrast to control lung fibroblasts, which contained 4.6- and 2.3-kilobase CSF-1 mRNAs, only the 4.6-kilobase species was detected in op/op cells. An alteration in the CSF-1 gene is strongly implicated as the primary defect in op/op mice because they do not contain detectable CSF-1, their defect is correctable by administration of CSF-1, the op locus and the CSF-1 gene map within the same region of mouse chromosome 3, their CSF-1 mRNA biosynthesis is altered, and the op/op phenotype is consistent with the phenotype expected in a CSF-1 deficient mouse. PMID- 2191303 TI - Crystal structure of an active form of RAS protein, a complex of a GTP analog and the HRAS p21 catalytic domain. AB - Normal RAS proteins play a key role of molecular switch in the transduction of the growth signal from extracellular to intracellular space. The state of the switch is "on" when GTP is bound and "off" when GDP is bound to the protein. The crystal structure of a complex between a nonhydrolyzable GTP analog and the catalytic domain of a RAS protein has been determined by a rotation-translation search method. The orientations and positions of four independent molecules have been determined using a single molecule as a probe in the search. The crystal structure reveals that the gamma phosphate of the GTP analog induces extensive conformational changes on two loop regions of the protein. PMID- 2191304 TI - Cloning and sequence of two different cDNAs encoding 1-aminocyclopropane-1 carboxylate synthase in tomato. AB - 1-Aminocyclopropane-1-carboxylate synthase (ACC synthase; S-adenosyl-L-methionine methylthioadenosine-lyase, EC 4.4.1.14), the key enzyme in ethylene biosynthesis, was purified 5000-fold from induced tomato pericarp. ACC synthase activity was unambiguously correlated with a 45-kDa protein by two independent methods. Peptide sequences were obtained both from the N terminus after electroblotting and from tryptic peptides separated by reversed-phase chromatography. Mixed oligonucleotide probes were used to screen a lambda gt11 library prepared from RNA of induced pericarp tissue. Putative ACC synthase clones were isolated with a frequency of 0.01%. One of these contained a 1.9-kilobase insert with a single open reading frame encoding a polypeptide of 55 kDa. A second, partial cDNA clone was found that differed from the first one in 18% of its bases. Genomic Southern blotting suggests possible tandem organization of the two genes in tomato. The entire coding region was expressed in Escherichia coli and the denatured recombinant polypeptide was used to raise polyclonal antibodies. The antibody preparation both immunoinhibits and immunoprecipitates ACC synthase activity from an enriched tomato extract, confirming the identity of the clone. Northern blot analysis demonstrates that the ACC synthase messenger accumulation is coordinated with fruit ripening. PMID- 2191305 TI - Apheresis: past and present. PMID- 2191306 TI - A study of plasma exchange in TTP. The Canadian Apheresis Study Group. PMID- 2191307 TI - The role of von Willebrand factor (vWF) in thrombotic thrombocytopenic purpura (TTP) and the hemolytic-uremic syndrome (HUS). PMID- 2191308 TI - The platelet aggregating factor(s) of thrombotic thrombocytopenic purpura. AB - Thrombotic thrombocytopenic purpura is characterized by disseminated platelet aggregates throughout the microcirculation and a large body of clinical, experimental and pathological evidence implicates in vivo platelet aggregation as being pivotal in the disease. For this reason considerable energy has been spent by many investigators to identify a platelet aggregating factor. The understated reason for these studies is that the characterization of such a factor could lead to the subsequent identification of a medication or a plasma factor that could neutralize the aggregating factor. Although a platelet aggregating factor has been suspected to play a causal role in TTP for almost 50 years, only in recent years have investigators systematically attempted to identify such a factor. One group has identified a 37 kD protein in the plasma of TTP patients which can initiate platelet aggregation through a unique pathway of aggregation and this factor can be inhibited by normal IgG. The other group of workers (ourselves) have provided evidence that the platelet aggregating factor of TTP is calpain. Thus, the very nature of the aggregating factor, and by implication its inhibitors, is very different for the two groups, and it may take other investigators to resolve whether there are multiple platelet aggregating factors of TTP. Nonetheless, it is apparent that recent research has dramatically improved our understanding of this uncommon but important disorder and it is possible that such investigations will lead to more successful treatments of this condition. PMID- 2191309 TI - Advances in the treatment of TTP. PMID- 2191310 TI - Immunosorptive apheresis of LDL. PMID- 2191311 TI - Mobilisation of tissue cholesterol by apheresis. PMID- 2191312 TI - Clinical effects and new evaluation trials of plasmapheresis for FH--computed quantitative coronary angiography and MRI changes in Achilles tendon. PMID- 2191313 TI - Therapeutic trial of low density lipoprotein apheresis (LDL-A) in conjunction with double filtration plasmapheresis (DFPP) in drug-resistant nephrotic syndrome due to focal glomerular sclerosis (FGS). PMID- 2191314 TI - Plasma exchange and an immunosuppressive regimen in primary biliary cirrhosis. PMID- 2191315 TI - Rationality of plasma exchange therapy based on periodic liver CT volume calculation in patients with fulminant hepatitis. PMID- 2191316 TI - Plasma exchange in acute renal transplant rejection. PMID- 2191317 TI - Plasma exchange in transplant rejection. PMID- 2191318 TI - Plasma exchange in rapidly progressive glomerulonephritis. PMID- 2191319 TI - Treatment of rapidly progressive glomerulonephritis by plasma exchange and methylprednisolone pulses. A prospective randomized trial of cyclophosphamide. Interim analysis. The French Cooperative Group. PMID- 2191320 TI - Role of therapeutic plasmapheresis in chronic inflammatory demyelinating polyneuropathy. AB - Therapeutic plasmapheresis is an effective therapy in the management of CIDP. A varying percentage of patients, approximately 30 to 60%, may benefit from the treatment. The optimal frequency and volume of PE need to be clarified, but, taking into account the heterogeneity of the disease, a too rigid approach should be avoided. According to our experience, neither morphological findings on sural nerve biopsy, nor conduction slowing, conduction block, or the amount of spontaneous activity on needle electromyography in a weak muscle correlated clearly with the later outcome of PE. Possibly our patient number is too small to provide any statistically significant predictor of outcome. In our opinion it is essential to combine plasmapheresis with effective immunosuppression to avoid a rebound with overshooting synthesis of putative pathogenic antibodies or factors. Finally, IA with T-PVA columns has proven effective in single, case-controlled patients with CIDP. It may be a promising supplement to PE avoiding the need and risks of protein replacement. PMID- 2191321 TI - Immunosorbent treatment in myasthenia gravis. PMID- 2191322 TI - Immunoadsorption (IA) versus plasma exchange (PE) in multiple sclerosis--first results of a double blind controlled trial. PMID- 2191323 TI - Chronic ITP as a model for immunization by platelets. AB - In summary, ITP is an autoimmune disorder due to the development of autoantibodies which in the majority of cases are directed against normal platelet membrane glycoproteins. The autoantibody binds to both platelets and megakaryocytes. The binding to platelets can cause phagocytosis by the immune system via an Fc receptor mechanism and in addition can activate the complement pathway which could cause more efficient phagocytosis or in vivo cell lysis. It seems likely that antibody bound to megakaryocytes might influence platelet production as well. At the present time, the immunoregulatory defect which results in this autoimmune disorder is unknown. PMID- 2191324 TI - Induction of remission in severe SLE after plasma exchange synchronized with subsequent pulse cyclophosphamide. PMID- 2191325 TI - Plasma exchange in Graves' ophthalmopathy. PMID- 2191326 TI - Plasma exchange in management of severe acute poisoning with Amanita phalloides. PMID- 2191328 TI - Successful procedure for plasmapheresis and immuno adsorption treatment. PMID- 2191327 TI - Treatment of severe Behcet's disease by plasma exchange with or without immunosuppressive drugs. Long term follow-up. PMID- 2191329 TI - Pharmacokinetics of cisplatin (CIS) during double filtration plasmapheresis (DFPP). PMID- 2191331 TI - Plasma exchange in immunological disease. PMID- 2191330 TI - Platelet function, surface structure and antigenicity. PMID- 2191332 TI - Plasma exchange and intravenous immunoglobulin infusion: antagonistic effects on mononuclear phagocyte functions with potential implications for therapy. PMID- 2191333 TI - Immunomodulation of cancer with activated cytotoxic leukocytes. PMID- 2191334 TI - LAK cells in cancer therapy--European results. PMID- 2191336 TI - Protein A immunoadsorption: immunomodulatory effects. PMID- 2191335 TI - Extracorporeal photochemotherapy for CTCL. PMID- 2191337 TI - Alloimmunization by leukocyte-rich or leukocyte-poor random single donor platelets. PMID- 2191338 TI - Review of definitions and mechanisms of refractoriness to platelet transfusions. PMID- 2191339 TI - Mononuclear cell (MC) functions by cryofiltration (CF) in rheumatoid arthritis (RA). PMID- 2191340 TI - Clinical aspects of biocompatibility issues on apheresis. PMID- 2191341 TI - Hematopoietic growth factors: a summary of their biology in tissue culture, animals, and clinical trials. PMID- 2191343 TI - Cellular support of the marrow transplant recipient. PMID- 2191342 TI - LAK cell therapy--clinical studies and future potential. PMID- 2191344 TI - [Hyperbaric oxygenation therapy and cicatrization]. AB - HOT is a very useful therapeutic addition in chronic wounds presenting a healing problem and for which usual treatment were unsuccessful. In order to be fully effective, HOT must be included in a strategy of care, taking into account, not only the wound itself but the underlying disease. Peripheral delivery of oxygen and induction of tissue hyperoxygenation with HOT may be verified by measurement of the TcPO2 under HOT. The predictive value of these measurements is helpful in the decision for treatment and its management. PMID- 2191345 TI - [Significance of Doppler echography of the external saphenous vein. A clinical comparison]. AB - The role, and the importance of the short saphenous vein, too often relegated at the background, in varicose disorders of the lower limbs: the numerous variations of its termination and association with gastrocnemian veins disorders are source of therapeutics failure. The popliteal fossa is for the best clinician a trap, origin of therapeutic mistakes. It seems to us usefull to compare the conclusion of clinical examination and echo-Doppler investigation. PMID- 2191346 TI - [Recommendations for vocabulary standardization and evaluation criteria in venous pathology]. PMID- 2191347 TI - [Practical aspects of wound healing in venous pathology]. PMID- 2191348 TI - [Treatment of intractable venous ulcer]. AB - Before describing the various treatments of these ulcers, the author discusses their etiological process. He emphasizes that superficial venous insufficiency is the result of a deep venous insufficiency which alters and deteriorate the cellular metabolism. In fact, the chronic hypertension is transmitted to the capillary network, often with irreversible consequences. The author analyzes the healing process: inflammatory phase followed after 2 weeks by the appearance of fibroblasts, wound contraction and epithelialization. The third phase, so-called stabilization phase, lasts between 6 and 12 months. The treatment varies according to the etiology. It is mostly a matter of experience in order to avoid allergenic treatments. PMID- 2191349 TI - [Physical treatment of venous edema. Physiopathological review]. PMID- 2191350 TI - [Activities of the leg muscles in daily life]. AB - This article is the result of an electromyographic analysis of the leg and thigh muscles in a standing position, during walking, pedalling on an ergocycle and during movements when venous return is activated. In a standing position, the leg muscles show no intermittent activity; while standing on the tip of the toes, the activity of the calf muscles is almost maximum; during walking and pedalling, the muscles are contracted intermittently and alternatively but also with non negligible periods of contraction. PMID- 2191351 TI - [Effect of respiratory movements on the venous return in the legs]. PMID- 2191352 TI - [Homage to Mario Vigoni 1900-1989]. PMID- 2191353 TI - Sixty-third president of APS. PMID- 2191354 TI - [Recent advances in bisbenzylisoquinoline alkaloids]. PMID- 2191355 TI - [Feigned experiences as the border between delusion and ego disturbances]. PMID- 2191356 TI - Models of disease and the diagnosis of schizophrenia. AB - DSM-III criteria for schizophrenia represent a significant advance in diagnostic reliability and relevance to course and treatment outcome. However, the underlying, predominantly biomedical model, if exclusively applied, encourages the making of more malignant diagnoses and in particular the over-diagnosing of schizophrenia. This occurs by virtue of an associated declining interest in the content and context of symptoms, a disavowal of "psychology" and a failure of empathy. A psychodynamic viewpoint can help to redress the diagnostic imbalance that the use of the biomedical model can engender. PMID- 2191357 TI - Depersonalization and meditation. AB - From a review of the literature on meditation and depersonalization and interviews conducted with six meditators, this study concludes that: 1) meditation can cause depersonalization and derealization; 2) the meanings in the mind of the meditator regarding the experience of depersonalization will determine to a great extent whether anxiety is present as part of the experience; 3) there need not be any significant anxiety or impairment in social or occupational functioning as a result of depersonalization; 4) a depersonalized state can become an apparently permanent mode of functioning; 5) patients with Depersonalization Disorder may be treated through a process of symbolic healing- that is, changing the meanings associated with depersonalization in the mind of the patient, thereby reducing anxiety and functional impairment; 6) panic/anxiety may be caused by depersonalization if catastrophic interpretations of depersonalization are present. PMID- 2191358 TI - Radiology and the new TNM classification of tumors: the future. AB - The latest edition of the TNM classification of tumors reflects advances in radiologic imaging such as computed tomography, magnetic resonance imaging, and endosonography. These modalities have increased the significance of clinical staging by enabling staging to be performed earlier. Thus, therapeutic decisions can be made before rather than during surgery. This review highlights important changes in the new TNM classification, relates them to imaging modalities, and emphasizes the role of the radiologist in clinical staging. PMID- 2191359 TI - Diagnostic approach to hepatic hemangiomas. PMID- 2191360 TI - Sigmoid diverticulitis: diagnostic role of CT--comparison with barium enema studies. AB - The diagnostic value of computed tomography (CT) and barium enema (BE) studies was evaluated prospectively in hospitalized patients with the presumptive diagnosis of acute sigmoid diverticulitis based on the presence of left-lower quadrant pain and tenderness, fever, and leukocytosis. Of 56 patients, 11 had sigmoid diverticulitis confirmed at surgery and 16 by clinical response to medical therapy. CT, performed in all diverticulitis patients, had positive results in 93% (25 of 27). These compared favorably with BE study results, of which 80% (20 of 25) were positive. Neither examination had false-positive results. In the 29 patients who did not have diverticulitis, an alternative diagnosis was made by means of CT in 20, but in only three by means of BE studies. Many of the extracolonic abnormalities recognized at CT were clinically unexpected and necessitated emergency surgery. The excellent sensitivity and specificity of CT coupled with its versatility in the detection of extracolonic disease give it an advantage over contrast enema studies for diagnosis of sigmoid diverticulitis. CT should be the initial study in acutely ill patients, especially when the clinical features are atypical for sigmoid diverticulitis. PMID- 2191361 TI - Relationship between stone motion, targeting, and fragmentation during experimental biliary lithotripsy. AB - In vitro experiments in an anthropomorphic phantom were performed to clarify the relationship between stone motion, targeting, and fragmentation. Stone motion was minimized by pinning the stone against the dependent wall of a mock gallbladder cavity during shock wave treatment. Fragmentation was most effective (probably due to increased cavitation effects) when the shock wave traversed fluid at the point of its impact with a stone. The results suggest that treatment with the patient in the supine or oblique position may produce a better outcome than treatment in the prone position. Buoyant stones exhibited the greatest motion, which was often to-and-fro in nature. Although restricting the size of the mock gallbladder cavity reduced stone motion, maintaining a 1-cm fluid path was beneficial for achieving optimal pulverization. PMID- 2191362 TI - US-guided percutaneous laser ablation of liver tissue in a chronic pig model. AB - The authors evaluated the safety of ultrasound (US)-guided percutaneous ablation of liver tissue using a neodymium-yttrium-aluminum-garnet (Nd:YAG) laser fiber placed through a skinny needle. The US appearance of the lesion was correlated with the pathologic findings in 19 pigs killed at 1-7 weeks. A 20-gauge needle was percutaneously placed in the liver, and a fiber with a 0.5-cm cladding stripped tip was inserted. The Nd:YAG laser was fired for 6 minutes at 1-4 W. The early sonographic appearance was recorded, and the US appearance before the pigs were killed was correlated with the gross and histopathologic findings. There were no cases of abdominal bleeding or infection. Mild transient changes in liver function were seen. An initial strong echogenic focus decreased slightly in echogenicity for 10 minutes and then stabilized. Over 1-7 weeks, the 1-cm diameter lesion decreased in size and developed an echogenic rim that correlated with a peripheral zone of inflammatory repair around a small central cavity and zone of necrosis. US-guided laser ablation of liver tissue is safe in this pig model, and the US appearance corresponds to a process of repair and removal of necrotic liver tissue. PMID- 2191363 TI - The benefits of percutaneous cholecystostomy for decompression of selected cases of obstructive jaundice. AB - Eleven selected patients with obstructive jaundice underwent percutaneous cholecystostomy (PC) for decompression. Ten of these patients had the constellation of distal common duct obstruction, nondilated or minimally dilated intrahepatic ducts, and a distended gallbladder; one patient with a bleeding dyscrasia had moderately dilated intrahepatic bile ducts. All procedures were successful and effective, and 10 of 11 cholecystostomies were performed within 5 15 minutes. No specific complications occurred. The success, ease, and safety of the procedure indicate primary use of PC for biliary decompression when the intrahepatic bile ducts are minimally dilated or nondilated, because standard transhepatic biliary drainage may be difficult in these cases. Because cannulation of the cystic duct and hence internalization through the tumor may be difficult, PC may be most valuable preoperatively, or before standard percutaneous biliary drainage, or as an alternative to endoscopic drainage. This is a rapid and safe method with which to achieve biliary decompression, especially with minimally dilated or nondilated intrahepatic bile ducts. PMID- 2191364 TI - Color Doppler signals from breast tumors. Work in progress. AB - The color Doppler signals in 60 patients with breast masses were assessed subjectively, and a regional grading method was developed for quantitation of displayed blood vessel density. Among 21 patients with breast carcinoma, moderate or high flow was demonstrated in all but one, with an average of 0.5 vessels per square centimeter and color pixels occupying 12.2% of the image area. Among 33 patients with benign disorders, no flow was demonstrated in 25 and slight to moderate flow was seen in five, with an average of 0.01 vessels per square centimeter, occupying 0.8% of the image area. Cancers as small as 10 mm in diameter were positive for flow. High-velocity flow was seen only in malignancies; it was observed in four cases and may have been due to arteriovenous shunting. Flow was less readily detected in recurrent tumors; two of seven tumors were weakly positive. Color Doppler shows promise as an adjunct to ultrasound imaging in the differential diagnosis of breast lesions. PMID- 2191365 TI - Mild lateral cerebral ventricular dilatation in utero: clinical significance and prognosis. AB - The medical records of 55 fetuses with sonographically diagnosed mild ventriculomegaly (MVM) were reviewed to assess prognosis. Fetuses were divided into two groups based on the presence or absence of sonographically detected associated fetal anomalies: 13 had no other anomalies detected (isolated MVM), and 42 had concomitant neural axis and visceral anomalies (nonisolated MVM). Mortality was 83% among fetuses with nonisolated MVM and 38% among fetuses with isolated MVM (P less than .005). If terminated pregnancies are excluded, only one of nine (11%) fetuses with isolated MVM died, compared with nine of 16 (56%) fetuses with nonisolated MVM (P less than .005). There are 15 living children: Nine (60%) are developmentally normal at 6-30 months of follow-up (six had isolated MVM), three (20%) are or are likely to be abnormal, and we were unable to follow up three (20%). Fetal anomalies were missed in 11 of 30 (37%) fetuses with detailed follow-up. However, this would have changed the classification from isolated to nonisolated MVM in only one case. Thus, in 54 of 55 cases (or 29 of 30 cases with detailed follow-up), fetuses were accurately classified as having isolated or nonisolated MVM. The authors conclude that sonographically isolated MVM is associated with a significantly better prognosis than nonisolated MVM, and fetuses can be classified accurately based on prenatal sonograms. PMID- 2191366 TI - Percutaneous treatments for biliary diseases. AB - Percutaneous treatment of biliary disease was administered in 173 cases, mainly among high-risk or elderly patients. Diagnosis was acute cholecystitis in 32 cases, acute cholangitis in 16, hepatic abscess in five, gallbladder stones in 28, common bile duct stones in 11, intrahepatic stones in five, malignant obstructive jaundice in 61, and benign biliary stenosis in 15. The treatment was successful in 158 of 173 cases (91.3%). Complications were encountered in 17 (9.8%). Most of these occurred during the initial period and were mild and controllable with conservative treatments. There were two deaths (1.2% of patients); one was not related to the procedure. These data suggest that percutaneous treatments are safe and effective even among elderly or high-risk patients with biliary diseases. PMID- 2191367 TI - David and Goliath. PMID- 2191368 TI - US guidance of interventional procedures. PMID- 2191369 TI - Is it calcification of the ductus venosus or calcification of the umbilical vein? PMID- 2191370 TI - Is it calcification of the ductus venosus or calcification of the ligamentum teres? PMID- 2191371 TI - Endovaginal sonography in very early pregnancy: new observations. PMID- 2191372 TI - Endovaginal US: demonstration of cardiac activity in embryos of less than 5.0 mm in crown-rump length. AB - The authors reviewed the endovaginal ultrasonographic (US) findings for 96 patients with embryos with crown-rump lengths of less than 5.0 mm. Of the 71 patients with adequate follow-up, initial endovaginal US demonstrated cardiac activity in 46 embryos and no cardiac activity in 25. Initial endovaginal US failed to demonstrate cardiac activity in five of 40 normal embryos, three with crown-rump lengths of less than 2.0 mm and two, between 2.0 and 3.9 mm. Endovaginal US identified cardiac activity in all 12 normal embryos with crown rump lengths of 4.0-4.9 mm. The presence of cardiac activity was associated with a 24% risk of spontaneous abortion. In embryos between 2.0 and 4.9 mm in crown rump length, absent cardiac activity was associated with a 91% risk of abortion. All 17 patients with vaginal bleeding and embryos demonstrating no cardiac activity subsequently aborted. The embryonic yolk sac was absent in 35% of patients who subsequently aborted. Variation outside of the 95% confidence limits of the mean for crown-rump length compared with mean gestational sac diameter and yolk sac diameter was also helpful in predicting an abnormal outcome. Nonvisualization of cardiac activity at endovaginal US in embryos less than 4.0 mm in crown-rump length may be normal and warrants follow-up US examination. PMID- 2191373 TI - Placental hypoechoic-anechoic areas and infarction: sonographic-pathologic correlation. AB - High-resolution ultrasound (US) and pathologic analysis were used to define the relationship between placental hypoechoic-anechoic areas, frequently seen in the third trimester, and the clinically significant entity of placental infarction. Placentas were obtained from three groups of patients: those prospectively demonstrating one or more placental hypoechoic-anechoic areas greater than or equal to 1 cm in diameter on third-trimester sonograms (n = 14), those with risk factors for vascular disease (n = 12), and control patients without risk factors (n = 16). Pathologic analysis demonstrated significantly more infarcts in patients with risk factors than in control patients (17 vs three, P = .047). Of a total of 22 infarcts from all three groups, 19 (86%) were isoechoic to viable placenta and therefore not detected with US. The three infarcts identified with US contained hypoechoic or anechoic foci of fibrin or hemorrhage. Of 26 placental hypoechoic-anechoic areas 23 (88%) were decidual septal cysts or intervillous thrombosis without infarction. The authors conclude that nonhemorrhagic placental infarction cannot be identified with ex utero US and, by inference, that prenatal US is probably insensitive for detection of placental infarction. PMID- 2191374 TI - Intracorporeal calcifications after self-injection of papaverine. AB - Penile indurations were found at follow-up examination in six of 120 patients with erectile dysfunction who practice intracavernosal self-injection of papaverine-phentolamine. In four of these six, cavernosal calcifications were demonstrated by means of ultrasound (US) and radiography. Most of the calcifications were close to the site of injection, but some were more distant. Cavernosal calcifications must be considered a possible complication of self injection of papaverine-phentolamine. Baseline US and radiographic studies of the penis are advisable before starting treatment. PMID- 2191375 TI - Adrenal hemorrhage after liver transplantation. AB - During orthotopic liver transplantation, ligation and division of the right adrenal vein during recipient hepatectomy may lead to hemorrhagic infarction and/or hematoma formation in the right adrenal gland. Findings in seven liver transplant recipients included initially echogenic or anechoic suprarenal masses on ultrasound scans and inhomogeneous but predominantly hypoattenuating masses on computed tomographic scans. In patients who survived for 4 months or longer, hematomas resolved as early as 20 days and persisted as long as 11 weeks. There was autopsy proof of adrenal hemorrhage in three cases. The adrenal hematomas in this series produced no massive hemorrhages, adrenal insufficiency, or other clinical manifestations. Adrenal hemorrhage after liver transplantation should be recognized and specifically documented, but a hematoma that remains stable in size can be left alone. PMID- 2191376 TI - Sonographic evaluation of the placenta: importance of pathologic correlation. PMID- 2191377 TI - Definitive diagnosis of hepatic hemangiomas: MR imaging versus Tc-99m-labeled red blood cell SPECT. AB - Thirty-seven patients with 69 suspected hemangiomas found by means of computed tomography (CT) and/or ultrasound were studied with both 0.5-T magnetic resonance (MR) imaging and single photon emission CT (SPECT) with technetium-99m-labeled red blood cells. Using a criterion of "perfusion-blood pool mismatch," SPECT readers diagnosed 50 of 64 hemangiomas and all five "nonhemangiomas" (sensitivity, 78% [95% confidence interval, 0.664 - 0.864]; accuracy, 80% [0.69 - 0.877]). Qualitative analysis of lesion signal intensity on T2-weighted spin-echo MR images allowed readers to diagnose 58 of 64 hemangiomas and four of five nonhemangiomas (sensitivity, 91% [0.814 - 0.96]; accuracy, 90% [0.807 - 0.951]). Because of the significantly higher cost of MR imaging and its inability to categorically differentiate hemangiomas from hypervascular metastases, the authors consider SPECT to be the method of choice for diagnosing hepatic hemangiomas. MR imaging should be reserved for the diagnosis of lesions smaller than 2.0 cm and for those 2.5 cm and smaller adjacent to the heart or major hepatic vessels; in such cases MR imaging was found superior to SPECT. PMID- 2191378 TI - [Valvulopathies (VII). Indication of surgery in chronic aortic insufficiency]. PMID- 2191379 TI - The evaluation and management of corneal lacerations. AB - Corneal lacerations represent a significant portion of ocular trauma. Effective management of this type of injury involves a thorough evaluation to assess the severity of the injury and the development of a logical management plan. Minor corneal trauma may be handled on an out-patient basis with the use of contact lenses and tissue adhesives. Severe injuries generally require admission and surgical intervention. Utilizing kerato-refractive principles and new suture techniques, post-operative astigmatism can be minimized at the time of primary closure. PMID- 2191380 TI - Prediction of postoperative vision in eyes with severe trauma. AB - The single most important factor determining the potential for return of useful vision in severely injured eyes is the magnitude of damage incurred by the macula or optic nerve at the time of injury. Most gravely injured eyes have media opacities that prevent funduscopic examination. In such eyes, the flash visually evoked potential is the single best predictor of postoperative vision. The second most reliable predictor is the bright-flash electroretinogram. Ultrasonography is an important part of the preoperative assessment of injured eyes with opaque media, but is of less value than electrophysiological testing in predicting postoperative vision in eyes with major trauma. PMID- 2191381 TI - Posterior segment manifestations of ocular trauma. AB - Nonpenetrating or blunt ocular trauma, orbital trauma and systemic trauma may cause a variety of posterior segment abnormalities. Blunt ocular trauma may cause damage to the retina (commotio retinae), retinal pigment epithelium (retinal pigment epithelial edema), choroid (choroidal rupture) and optic nerve (optic nerve evulsion) alone or in combination. Traumatic macular holes and retinal detachment or dialysis may also occur after blunt ocular trauma. Trauma to the orbital tissues adjacent to the globe can cause concussive forces with damage to multiple structures within the eye (chorioretinitis sclopetaria). Systemic trauma may result in diffuse retinopathy (Purtscher's retinopathy, shaken baby syndrome) or localized retinal abnormalities (whiplash retinopathy, fat embolism syndrome). Alterations in intravascular (Valsalva retinopathy) or intracranial pressure (Terson's syndrome) due to a variety of causes may result in preretinal or vitreous hemorrhage and associated visual loss. The purpose of this report is to review each of these entities of traumatic posterior segment abnormalities. PMID- 2191382 TI - Intraretinal foreign bodies. Management and observations. AB - Foreign bodies embedded in the retina and choroid such that they cannot be extracted by a magnet and require vitreous surgical techniques for removal comprise a distinct sub-type of retained intraocular foreign body (IOFB). A retrospective evaluation of 16 such intraretinal foreign bodies (IRFBs), suggests that these injuries are frequently accompanied by extensive ocular damage, including corneal perforation, disruption of the lens, significant vitreous hemorrhage, retinal and choroidal hemorrhage and retinal detachment, all of which require immediate surgical attention. Delayed cataract and retinal detachment are often observed in these cases. More than 60% of this series developed macular pucker after IRFB removal. Visual outcomes were discouraging, with seven patients (44%) retaining only 20/200 or worse visual acuity. This review suggests that the structural and visual outcomes of such eyes are uncertain, are the products of complex processes involving numerous technical elements other than sophisticated surgery and prompt removal of the foreign body. PMID- 2191383 TI - Intraoperative control of hemorrhage in penetrating ocular injuries. AB - Control of intraoperative hemorrhage is critical during vitreoretinal surgery for penetrating ocular injuries. Methods to control bleeding include: (1) raising the intraocular pressure, (2) intraocular diathermy, (3) fluid/gas exchange, (4) choice of irrigating solution, (5) addition of thrombin to the infusion solution, (6) endophotocoagulation, (7) silicone oil injection, (8) sodium hyaluronate injection. A combination of these various methods will almost always control bleeding in each case. PMID- 2191385 TI - Hyphema: diagnosis and management. AB - The management of traumatic hyphema has been controversial for many years. Treatments designed to prevent secondary hemorrhage have been proposed in the literature, then later abandoned when prospective studies failed to support them. In the last several years, published studies have demonstrated the efficacy of antifibrinolytic agents in the prevention of secondary hemorrhages. These studies have left unanswered some questions, however, such as whether antifibrinolytics are as effective in children as adults, in white patients as black, and in patients with normal hemoglobin as well as those with sickle cell hemoglobinopathies. The successful treatment of patients with hyphemas hinges on identification of risk factors, proper medical management and prompt surgical intervention when medical therapy fails. PMID- 2191384 TI - Management of traumatic rupture of the globe in aphakic patients. AB - We report the successful treatment of three cases of traumatic ruptures of the globe complicated by massive choroidal hemorrhage, uveal prolapse and retinal detachment. All three of the eyes were aphakic prior to injury and all patients were age 64 or older. The presenting visual acuity in all patients was light perception. The blunt injury in each case caused a wound dehiscence at the site of previous cataract extraction. All injuries were associated with uveal prolapse. Secondary surgical intervention was performed when the hemorrhagic choroidal detachments had decreased as demonstrated by echography in the suprachoroidal space, occurring at an average of 14 days after injury. The management consisted of surgical drainage of the choroidal hemorrhage combined with vitrectomy and silicone oil injection. Successful reattachment of the retina was achieved in all cases. Postoperative epiretinal membranes formed in two cases but all were anatomically successful at six months. Final visual acuities varied from 20/70 to 1/200, visual acuity being a function of secondary contusive damage to the retina and choroid. We believe that in eyes sustaining severe blunt injuries resulting in rupture of the globe complicated by massive choroidal hemorrhage and retinal detachment, properly timed external drainage of the choroidal hemorrhage combined with pars plana vitrectomy and silicone oil injection is a useful approach. PMID- 2191386 TI - Evolving concepts in the management of posterior segment penetrating ocular injuries. AB - Advances in understanding the pathobiology of secondary complications after posterior segment penetrating ocular injuries along with progress in instrumentation and surgical techniques have provided a powerful means to salvage certain eyes that would otherwise be lost. Further progress will probably include the use of pharmacologic agents that interfere with fibrocellular proliferation, as well as better delineation of the methods and timing of surgery. PMID- 2191387 TI - Controversies in the management of posterior segment ocular trauma. AB - Despite steady advances in surgical instrumentation and technique, ocular trauma continues to be a leading cause of visual loss in the United States. Almost half of the patients with posterior penetrating injuries are left with severe visual impairment. Controversy persists over the optimal management of the injured eye, including the proper use of prophylactic antibiotics, prophylactic cryopexy, and prophylactic scleral buckling. The role and timing of vitrectomy surgery in severe ocular trauma also remain topics of considerable debate, as does the role of vitrectomy in the management of magnetic intraocular foreign bodies. Each of these issues is discussed, with particular emphasis on conflicting views presented in the relevant literature. PMID- 2191389 TI - Autonomic functions: the other nervous system. PMID- 2191388 TI - Early repair of complex orbital fractures. AB - Complex orbital fractures consist of fractures of the orbital rim and walls in two or more places and may be associated with more extensive facial fractures. Previously, delayed repair was the standard approach. Techniques of craniofacial surgery allow earlier reconstruction with more accuracy and stability. Enophthalmus, dystopia and facial contour deformities are avoided, and the final result improved. A new standard has been established. Three factors are important in attaining improved results. Three-dimensional CT scanning is used to obtain a comprehensive assessment of the injury, to plan reconstruction pre-operatively, and to assess the reconstruction post-operatively. Secondly, complete exposure of the facial skeleton is necessary and is achieved by the use of a coronal incision, frontal flap, infraorbital incision, and intraoral upper sulcus incision. Thirdly, cranial bone grafting is used to reconstruct orbital floors and severely comminuted or missing bones. Finally, the use of mini-plates and lag screws provides improved accuracy and stability of the reconstruction. PMID- 2191390 TI - Autonomic control of the cardiovascular system. PMID- 2191391 TI - Autonomic dysfunction of the eye. PMID- 2191392 TI - Megaesophagus in the dog and cat. PMID- 2191393 TI - The anatomy of the visceral and autonomic nervous systems. AB - The visceral nervous system has several levels of anatomical organization. Individual viscera, including the heart and the intestines, have neural tissue embedded in their walls that is capable, under some circumstances, of a truly autonomic self-regulation of that organ's activity. This self-regulation will not respond to all the varying needs of the organ control, particularly when external or internal changes affect the whole animal. The parasympathetic, sympathetic, and visceral afferent systems and their CNS connections are the next level of reflex neural organization. A greater degree of central regulation is managed at this level. The third level of visceral control is located in the brainstem and includes the hypothalamus, parts of the reticular formation, and cardiorespiratory centers in the medulla. These visceral upper neuron centers exert a high degree of control over the parasympathetic and sympathetic LMN centers of the brainstem and spinal cord. The reticulobulbar and reticulospinal pathways are the means by which the visceral upper motor neurons communicate with the LMN systems. The hypothalamus-hypophyseal system exerts control by releasing hormones to act on distant target organs. The highest level of organization of visceral function takes place in the limbic system. The limbic system is in a position to integrate sensory information originating from both within (interoceptive) and outside (exteroceptive) the animal. Associations are made at this level and with the help of cortical association areas, memory is integrated with these sensations. The limbic system is then able to influence the hypothalamic and medullary centers as well as the somatic motor centers to develop the appropriate responses for the preservation of the animal. PMID- 2191394 TI - The enteric nervous system: function, dysfunction, and pharmacological manipulation. PMID- 2191395 TI - Disorders of the urogenital system. PMID- 2191396 TI - Feline dysautonomia. PMID- 2191397 TI - Canine dysautonomia. PMID- 2191398 TI - Intracavernous drug administration: its role in diagnosis and treatment of impotence. PMID- 2191399 TI - Diagnosis and management of corporal veno-occlusive dysfunction. PMID- 2191400 TI - External penile appliances for management of impotence. PMID- 2191401 TI - The role of vascular surgery in arteriogenic and combined arteriogenic and venogenic impotence. AB - Currently, the only procedure that may be ready for clinical application in arteriogenic impotence is the retrograde revascularization operation for patients who have been shown to have localized obstruction of the internal pudendal artery. This applies almost exclusively to young healthy men with impotence due to pelvic trauma. The concept that perineal trauma causes localized obstruction of the penile artery is controversial. Because the best candidates for penile revascularization are young healthy men with localized, rather than diffuse, arterial pathology and with the absence of vascular risk factors, the overall role for treatment of arteriogenic or combined arteriogenic and venogenic impotence by penile revascularization is very limited. For patients with impotence following pelvic and possibly perineal trauma, as well as occasional patients with arteriosclerosis who wish to be considered for penile revascularization, evaluation should begin with screening intracavernous pharmacodiagnosis using papaverine with or without phentolamine, or prostaglandin E1. If a poor response occurs, identification of venous pathophysiology by cavernosometry and identification of arterial pathophysiology by dynamic infusion cavernosometry and/or duplex sonography of the corpus cavernosum should be undertaken. If there is no venous pathology, penile arteriography must be done to design an anatomically rational revascularization operation. In the future, improved results of penile vascular surgery may occur if we can develop a clearer understanding of the physiology and pathophysiology of erection, improved diagnostic techniques, and a better selection of surgical candidates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2191402 TI - The use of penile prostheses in erectile dysfunction. PMID- 2191403 TI - Pathophysiology of erectile dysfunction. PMID- 2191404 TI - The clinical evaluation of the patient presenting with erectile dysfunction: what is reasonable? PMID- 2191405 TI - [Human rights and procreation]. AB - Assisted procreation raises several problems in relation to Human Rights. The first owes to gamete donation which introduces foreign genetic material into the family. In this respect, conflicting rights of the child, the parents and the donor, are diversely perceived in different cultures. Another difficulty concerns the status of the human embryo cultured in vitro. An analysis based on a relational definition of the human person indicates that the embryo cannot reasonably become endowed with legal rights, if it does not represent the project of having a child. Assisted procreation, moreover, raises the question of the right to parenthood, not only of sterile couples but also of female homosexuals and women without partners. It also reactivates the debate on Human Rights in relation to technocratic power. PMID- 2191406 TI - [Cardiorespiratory resuscitation: what is the mechanism of cardiac massage?]. AB - The mechanism involved in the generation of cardiac output during cardiopulmonary resuscitation (CPR) are complex and still controversial. This article reviews the concepts of "cardiac pump" and "thoracic pump", which can both be implicated, before presenting the practical implications as well as the possibilities of development of new CPR techniques. PMID- 2191407 TI - [Sudden death in young athletes]. AB - Sudden death before the age of 35 is often the consequence of a congenital heart disease. The principal congenital causes are hypertrophic cardiomyopathy and congenital abnormalities of the coronary arteries. The authors propose a programme for detecting those sportsmen who are at risk, giving indications and contra-indications about taking part in competitions. Finally they suggest strategies to prevent the occurrence of sudden death in our young sportsmen. PMID- 2191410 TI - Proopiomelanocortin: alpha-amidated and related peptides. PMID- 2191409 TI - Immune deposits in articular cartilage of patients with rheumatoid arthritis have a granular pattern not seen in osteoarthritis. AB - Frozen sections of articular cartilage, obtained from patients with rheumatoid arthritis (RA) or osteoarthritis (OA) undergoing joint replacement, were stained with fluoresceinated specific antisera to IgG, IgM, IgA, C1q, C4, and C3. Specimens positive for IgG were examined for IgG subclasses using mouse monoclonal antibodies. IgG was present in 22 of 34 cartilage specimens obtained from patients with RA, and in 14 of these 22 patients, a granular pattern was present. IgM, IgA, C1q, and C3 when present showed a similar granular pattern. In articular cartilage of patients with RA, all IgG subclasses tended to be present. The remaining eight specimens positive for IgG from patients with RA had staining patterns also seen in patients with OA. IgG staining was present in 31 of 117 cartilage specimens obtained from patients with OA and none had the granular pattern seen in RA. Intermittent linear staining at the surface was the most common pattern seen in cartilage from patients with OA. The different patterns of immune deposits in articular cartilage in RA and OA suggest that antibodies with different specificities are present or that different mechanisms of immune deposit formation exist in these disorders. PMID- 2191411 TI - Isoelectric focusing of urinary metallothionein. AB - Isoelectric focusing of human urinary metallothionein at a pH range of 4.8 to 7.0 yielded a single protein band with a pI of 5.57 which co-migrated with authentic purified metallothionein I from human liver. Minimum pretreatment of the urine samples (160 ml) was needed. The preparatory steps included sample concentration with the original protein, enriched from 69 +/- 23 micrograms/ml to 2.0 +/- 1.4 mg/ml (+/- SD; n = 9), followed by heat treatment at 80 degrees C for 5 min (2.4 +/- 1.7 mg protein/ml). After focusing, the gels were stained with silver and the lanes were scanned with a laser scanner. Peak areas were used for quantitation with commercial beta 2-microglobulin as a standard. The urinary metallothionein ranged from 1.0 to 2.6 nmol/mmol creatinine, which is comparable with values reached by radio-immunoassay. PMID- 2191408 TI - beta 2-Microglobulin amyloidosis. A systemic amyloid disease affecting primarily synovium and bone in long-term dialysis patients. AB - A number of rheumatic disorders occur in patients on long-term hemodialysis treatment. In recent years a clinical syndrome comprising carpal tunnel syndrome, destructive arthropathy, and cystic bone lesions has been recognized in these patients. Congo-red staining and microscopy in polarized light reveal a high frequency of amyloid in the affected tissues. Amino acid sequence data of the isolated major amyloid fibril protein show its identity with beta 2 microglobulin. beta 2-microglobulin amyloid has a predilection for synovial tissues and bone, but visceral deposits may also occur indicating the systemic nature of the disease. The clinicopathological features, pathogenesis, and diagnosis of beta 2-microglobulin amyloidosis are reviewed, and the therapeutic and prophylactic measures discussed. The identification of beta 2-microglobulin as an amyloidogenic protein has in an important way contributed to the understanding of the mechanisms of amyloidogenesis in general and emphasized the complexity of amyloid disease and the diversity of proteins capable of forming congophilic fibrillar deposits in human tissues. PMID- 2191412 TI - Atherogenesis and the role of lipoproteins. PMID- 2191413 TI - Hypercholesterolaemia in the hypertensive patient. PMID- 2191414 TI - Functional abnormalities of the vascular endothelium in hypertension and atherosclerosis. PMID- 2191415 TI - The role of smooth muscle proliferation in atherogenesis. PMID- 2191416 TI - Atherosclerotic lesions in peripheral vessels? PMID- 2191417 TI - Antihypertensive therapy and blood lipids: calcium antagonists. PMID- 2191418 TI - Antihypertensive therapy and blood lipids: ACE inhibitors. PMID- 2191419 TI - Diet: opportunities and limitations. PMID- 2191420 TI - Drug therapy in dyslipidemia. PMID- 2191421 TI - Total mortality in cardiovascular risk factor intervention trials. PMID- 2191422 TI - Changing patterns of inflammatory bowel diseases. AB - Changes in the diagnosis, mode of presentation, localization, incidence, and prevalence of inflammatory bowel diseases have occurred since the 1930s. Some of the changes are spurious and reflect earlier and more accurate diagnosis as a result of technologic advances. Increased information and the development of medicosurgical teams have increased gastroenterologists' ability to manage Crohn's disease and ulcerative colitis. Associations for patients are making important contributions to the well-being of the patients. However, no major breakthrough in our understanding of the aetiology of the diseases has been achieved, and conservative treatment remains unchanged. PMID- 2191423 TI - Patterns of postoperative recurrence in Crohn's disease. AB - The most difficult problem in the management of Crohn's disease is that the condition is permanent and incurable. Even though most patients ultimately have resection surgery and are thereby greatly improved, in most cases the disease recurs within several years after the operation. This phenomenon of postoperative recurrence has been recognized for decades, yet there has been little agreement concerning such important issues as the frequency, rate, and risk factors of recurrent disease. The reasons for disagreement are primarily methodologic and fall into three major categories: 1) different definitions of recurrence; 2) different operative procedures; and 3) different statistical methods. Two factors in particular seem to exert the strongest influence on the rates of postoperative recurrence. One is the surgical procedure itself, with recurrences appearing faster and more frequently after anastomoses than after ileostomies. The second and perhaps more important factor is the behavior of the underlying disease. Data suggest that an aggressive fistulizing form of Crohn's disease brings patients to surgery sooner and is followed by a faster rate of postoperative recurrence and reoperation; the disease also tends to recur with fistulous complications similar to the original ones. By contrast, a more indolent obstructing form of Crohn's disease brings patients to surgery later and is followed by a slower rate of recurrence and reoperation; this form of disease tends to recur with obstructive complications. The recognition of these two different clinical forms of Crohn's disease may have important prognostic and even pathophysiologic implications. PMID- 2191424 TI - Immune events associated with inflammatory bowel disease. AB - Immunologic abnormalities have been implicated in the etiology of inflammatory bowel disease (IBD). Defects of systemic immunity and of local (intestinal) immunity have been studied. The numbers of T and B lymphocytes and their characteristics seem to vary with the disease, but no cause-and-effect relationship has been established. The presence of anticolon antibodies in patients with ulcerative colitis suggests that these antibodies could be involved in IBD, but they have also been found in other conditions. In the peripheral blood, abnormalities of cell-mediated immunity are inconsistent and suggest that they are not fundamental defects of the disease. The hypothesis that the inflammatory process is a result of immune-mediated intestinal tissue damage is being extensively studied. The high familial incidence of the disease suggests a role of histocompatibility locus antigens, but no reproducible association can be established. In vivo and in vitro studies of mucosal mononuclear cells have revealed abnormalities of immunoglobulin production, some types of cytotoxicity against gut-derived antigens, and altered lymphokine production associated with the disease. Further studies of the intestinal immune system would seem to be the most fruitful line of research. PMID- 2191425 TI - Role of rectal formulations: suppositories. AB - Mesalazine (5-aminosalicylic acid) suppositories are safe, effective, well tolerated, and well retained in patients with active distal proctitis. The best results are seen in patients with idiopathic ulcerative proctitis. Approximately 85% of these patients are healed within 4 weeks and virtually 100% by 10 weeks, with mucosal healing and complete loss of symptoms. Suppositories cover the last 20 cm of the rectum, as shown by technetium labelling. Maintenance therapy using suppositories alone--in doses varying from 500 mg every second bedtime to 1000 mg per day in divided doses--is at least as effective as oral sulphasalazine. Mesalazine suppositories are also useful in treating patients with Crohn's disease affecting the rectum, although the response rate is slower and healing is incomplete in half the patients treated. In the rare solitary rectal ulcer syndrome, mesalazine suppositories may be as efficacious as mesalazine enemas. Patient compliance and dramatic response even when conventional therapy has failed make an excellent case for mesalazine suppositories being the treatment of choice for distal ulcerative proctocolitis. PMID- 2191426 TI - Biosafety considerations in industries with production methods based on the use of recombinant deoxyribonucleic acid. AB - Since no occupational accidents or diseases have been attributed specifically to the use of constructions containing recombinant deoxyribonucleic acid (rDNA), this paper evaluates the occupational health risks in industries utilizing genetically manipulated organisms mainly on the basis of theoretical considerations. Bacteria, filamentous fungi, yeasts, and mammalian cells in culture are in use. For each of these systems the possible hazards are considered. Concerning microbial production systems, infections are regarded as the main problem, but the risk of infection is considered extremely low. As for cells in culture, only dormant viruses are regarded as problematic, but well defined production cell lines should not contain such undetected and dangerous viruses. Overall, the additional risks posed by rDNA-modified micro-organisms are minor. Only long-term observations can, however, confirm this assumption, and consequently the highest feasible containment measures should still be used in the years to come. PMID- 2191427 TI - Hypercoagulability: introduction and perspective. PMID- 2191428 TI - Current issues in laboratory diagnosis of bleeding disorders and hypercoagulable states. Dedicated to the memory of Anthony P. Fletcher, M.D. PMID- 2191429 TI - Overview of the hypercoagulable states. PMID- 2191430 TI - Laboratory diagnosis of antithrombin and heparin cofactor II deficiency. AB - Antithrombin activity should probably be determined in persons with early onset of recurrent thrombosis, especially if a family history is present. The initial screening test should be a heparin cofactor assay optimized to reduce the contribution of heparin cofactor II. If the heparin cofactor assay is low, an antigenic determination should be performed to rule out the possibility of an antithrombin variant. At the present time, there is insufficient evidence to recommend the routine determination of heparin cofactor II levels in patients with thrombosis. PMID- 2191431 TI - Laboratory diagnosis of protein C deficiency. PMID- 2191432 TI - Laboratory diagnosis of impairment of fibrinolysis in patients with thromboembolic disease. PMID- 2191433 TI - The epidemiology of human immunodeficiency virus and acquired immunodeficiency syndrome. PMID- 2191434 TI - Cancer in acquired immunodeficiency syndrome: an epidemiological assessment. PMID- 2191435 TI - Public health and community-related consequences of the human immunodeficiency virus epidemic. PMID- 2191436 TI - Biology and pathogenesis of retroviruses. PMID- 2191437 TI - Detection, prevention, and treatment of retroviral infections. PMID- 2191439 TI - Acquired immunodeficiency syndrome-associated non-Hodgkin's lymphoma. AB - The clinical picture is of aggressive high and intermediate grade lymphoma with extranodal presentation either as the first manifestation or during the course of HIV infection. The dramatic growth of tumors, leukopenia, opportunistic infections, and pre-existing AIDS-related problems of KS and chronic infections have made treatment extremely difficult. New regimens using short courses of chemotherapy, GM-CSF, and antiviral therapy have raised hopes that these measures will lead to improved survival. PMID- 2191438 TI - Epidemic Kaposi's sarcoma. AB - No significant impact of available treatments on survival among patients with epidemic KS has been demonstrated. Therefore, antitumor therapy now should be considered palliative. In the early stages of the disease, systemic treatment may not be needed, whereas advanced disease requires systemic treatment with one or more agents known to have antitumor activity. A complete therapeutic response is difficult to achieve and if such response is obtained, maintenance therapy may be necessary. The overall prognosis for survival in patients with epidemic KS appears to depend on the severity of immune suppression and HIV infection rather than on the neoplastic proliferation and tumor load. This is reflected in the new staging proposals for KS. Ultimately, the ideal treatment for the AIDS patient with KS will be a combination of antiretroviral therapy to suppress further effects of HIV, biological therapy to reverse the immunologic defects, chemotherapy to control tumor development, and hematopoietic growth factors to ameliorate treatment toxicities. PMID- 2191440 TI - Thrombocytopenia and human immunodeficiency virus-1 infection. PMID- 2191441 TI - The interrelationship between acquired immunodeficiency syndrome and cancer research. PMID- 2191442 TI - The clinical pharmacology of fluconazole. AB - The pharmacokinetic profile of fluconazole clearly distinguishes it from other antifungal agents; oral bioavailability is more than 90%, and plasma protein binding is 12%. The volume of distribution approximates that of total body water. Both peak and minimum plasma concentrations are linearly proportional to dose over a range of 50 to 400 mg. Fluconazole is metabolically stable. Renal clearance is the predominant route of elimination, with only 11% of a single dose excreted as metabolites. The mean elimination half-life is approximately 30 hours. Consequently, dosage requirements in the presence of renal insufficiency are predictable from and dependent on renal function. Fluconazole has been extensively studied regarding drug interactions that may occur during concomitant therapy with cimetidine, rifampin, warfarin, oral hypoglycemics, phenytoin, and cyclosporin A. Results indicate that fluconazole can be safely administered with these drugs, as well as a number of other commonly used drugs. PMID- 2191443 TI - Fluconazole treatment of fungal infections in the immunocompromised host. AB - Immunocompromised patients are predisposed to opportunistic fungal infections. Candidiasis is reported most frequently both as a localized infection (eg, oropharyngeal candidiasis) and as life-threatening systemic candidiasis. With relatively few antifungal agents in the clinical armamentarium, the optimal management of candidiasis remains controversial. Among the agents that are available, amphotericin B is difficult to administer, 5-fluorocytosine cannot be used alone due to the frequent emergence of resistant yeasts, and ketoconazole, which is effective for esophageal and oropharyngeal candidiasis, is not recommended for systemic candidiasis, especially in granulocytopenic patients. Recently, fluconazole, a new triazole antifungal agent, has been found to be active against Candida spp and is being studied in various clinical settings. In addition to its oral formulation, it is available for intravenous (IV) administration, which is a significant advantage in treating debilitated or noncompliant patients. In a randomized, double-blind study, we compared the efficacy of 100 mg/d oral fluconazole with that of 400 mg/d ketoconazole in cancer patients with oropharyngeal candidiasis. Although clinical and microbiological outcomes were similar for both groups, relapses occurred earlier in ketoconazole- than in fluconazole-treated patients. In another study, we administered fluconazole IV 100 to 300 mg/d to 13 patients, eight of whom had fungemia. Preliminary results are encouraging. Further studies of fluconazole as prophylaxis in granulocytopenic patients and as therapy for documented systemic candidiasis are under way. These studies are expected to define specific indications for fluconazole in immunocompromised patients. PMID- 2191444 TI - Prophylaxis of candidiasis in cancer patients. AB - Patients undergoing therapy for metastatic malignancies were randomly assigned to receive fluconazole or placebo as antifungal prophylaxis. Oropharyngeal candidiasis developed in 28% of 54 evaluable patients receiving placebo but in only 2% of 58 evaluable patients receiving fluconazole (P = .0003). Among patients receiving placebo, oropharyngeal candidiasis (thrush) occurred in 30% of those receiving antibiotic therapy and in 44% of those receiving adrenal corticosteroid therapy. Oropharyngeal candidiasis developed in 54% of the placebo patients who were colonized by Candida sp at the onset of prophylaxis. Fluconazole proved to be effective for prophylaxis of oropharyngeal candidiasis in susceptible patients and was well tolerated. PMID- 2191446 TI - [Nurses are nearly all alike]. PMID- 2191445 TI - Fungal infections in the pediatric cancer patient. AB - Chemotherapy, while undeniably effective in controlling or eradicating a variety of neoplasms, is also accompanied by a number of toxicities. Foremost among these is neutropenia, which places the pediatric cancer patient at risk for serious fungal infections. The fungal organisms most commonly responsible for infection in neutropenic children are Candida, Aspergillus, Mucor, and the Phycomycetes. Common sites of infection include the oral cavity, sinuses, lung, and bloodstream. Recently, candidal infection of the liver was recognized as a growing problem. Diagnosis of deep-seated fungal infections, such as pneumonia and hepatic candidiasis, is extremely difficult, often requiring open-lung or liver biopsy, which a patient's hematologic status may not permit. Because early treatment significantly improves prognosis, empirical antifungal therapy may be indicated in selected patients. Amphotericin B is currently the antifungal agent of choice against most fungal organisms. Antifungal efficacy studies based on animal models of disseminated candidal infection suggest that amphotericin B combined with 5-fluorocytosine (5-FC) is more effective than amphotericin B alone against most deep-seated Candida infections. The investigational drug, fluconazole, appears as effective as amphotericin B plus 5-FC in the prevention and early treatment of disseminated candidiasis, and clinical trials to assess this potentially important role for the new antifungal agent are now being initiated. PMID- 2191447 TI - [Florence in the year 1990]. PMID- 2191448 TI - Case report 612: Rhabdomyosarcoma of the right psoas muscle. PMID- 2191450 TI - [Medico-psycho-pedagogical centers. A little history]. PMID- 2191449 TI - Welfare reform: from illusion to reality. AB - Welfare reform is a concept that has a relatively narrow meaning in the United States, because it is associated with the Aid to Families with Dependent Children (AFDC) program. Since the 1960s, several attempts have been made to reform AFDC, but it was not until 1988 that the program was changed substantially. The alterations in the AFDC program reflect an ideological shift in American culture that is increasingly conservative. Social welfare policy as a whole has begun to reflect conservative values by emphasizing reciprocity, productivity, and familial responsibility. A myriad of important social welfare issues remain unresolved despite the new welfare reform bill of 1988. PMID- 2191451 TI - [Relaxation: at the risk of closeness]. PMID- 2191452 TI - Spinal cord compression in primary hyperparathyroidism. Report of a case and review of the literature. PMID- 2191453 TI - Osteochondroma of the thoracic spine. Report of a case and review of the literature. PMID- 2191454 TI - Talmudic and other ancient concepts of the number of vertebrae in the human spine. PMID- 2191455 TI - Surgical treatment of hematogenous vertebral Aspergillus osteomyelitis. AB - Three cases of Aspergillus fumigatas vertebral osteomyelitis failed courses of medical treatment. Each was subsequently treated with anterior vertebral debridement and posterior segmental spinal instrumentation. Despite poor nutritional and immune systems, resolution of the infection and subsequent anterior ankylosis occurred in each patient, with follow-up ranging from 1 to 3 years. If patients with aspergillus vertebral osteomyelitis do not respond to medical treatment, early surgical debridement and stabilization in combination with intravenous amphotericin B can lead to resolution and bony ankylosis. PMID- 2191456 TI - The role of interventional radiology for complications of cholecystectomy. AB - This report summarizes diagnostic and therapeutic radiologic procedures in 45 patients who suffered major complications from cholecystectomy. Complications were divided into (1) bile duct injury or ligation and (2) a variety of pathologic fluid collections. Specific lesions were bile duct injury (n = 6), accidental bile duct ligation (n = 12), ductal stricture (n = 12), abscess (n = 11), biloma (n = 7), hematoma (n = 5), infected pancreatic pseudocyst (n = 3), and stones (n = 2). Presenting problems were sepsis, jaundice, and intermittent cholangitis. The patients underwent 104 interventional radiologic procedures including 29 percutaneous transhepatic cholangiograms, 21 percutaneous biliary drainages, 12 balloon dilatations of strictures, drainage of 11 abscesses, 8 bilomas, 5 hematomas, and 3 pancreatic pseudocysts. Stones were removed by baskets in 2 patients; 12 pressure and perfusion studies were performed. One hundred of 104 procedures were successful; there was one failed biliary drainage, one unsuccessful stricture dilatation, one unsuccessful hematoma drainage, and one recurrent biloma. Thirty patients were spared another operation. The percutaneous procedures were beneficial although not curative in 14 of 15 patients who underwent reoperation; in those patients the procedures helped to establish a diagnosis, improve the patient's preoperative status, or serve as a landmark for the surgeon to locate and repair the ligated or injured duct. One patient died after reoperation, a 2.2% mortality rate. Sectional imaging studies combined with interventional radiologic procedures help to diagnose promptly and effectively treat major complications of cholecystectomy. These interventional procedures either cure the complication and obviate reoperation or aid the surgeon by relieving sepsis and jaundice before reoperation and providing an intraoperative guide for bile duct reconstruction. PMID- 2191457 TI - The effect of pancreatic polypeptide infusion on glucose tolerance and insulin response in longitudinally studied pancreatitis-induced diabetes. AB - Glucose intolerance is often associated with pancreatitis. Pancreatitis-induced diabetes represents a different clinical syndrome than type I and type II diabetes mellitus. Patients with pancreatitis-induced diabetes may be extremely sensitive to exogenous insulin, rarely develop ketoacidosis, and rarely exhibit classic diabetic complications, such as retinopathy, nephropathy, or accelerated vasculopathy. Pancreatic polypeptide (PP) deficiency has been implicated in the defect of glucose homeostasis found after pancreatitis. This study evaluated intravenous and oral glucose tolerance and insulin response to glucose loading, in the setting of pancreatitis, with and without short-term PP replacement. Dogs (n = 7) underwent pancreatic duct ligation (PDL) and were studied with and without PP infusion (2 micrograms/kg/hr) before PDL and at 1 week, 6 weeks, and 4 months after PDL by means of intravenous and oral glucose tolerance tests. Basal and bombesin-stimulated PP levels at 4 months after PDL were subnormal, verifying PP deficiency in these animals with pancreatitis. PP levels during PP infusion reproduced normal postcibal levels, averaging 897 +/- 40 pg/ml. Glucose tolerance, expressed as the glucose decay constant for the intravenous glucose tolerance tests and as the integrated glucose response for the oral glucose tolerance tests, deteriorated over time and was not improved by acute PP replacement. The integrated insulin response to glucose was not affected by PP. The acute infusion of PP at a dose that reproduces normal postprandial PP levels fails to improve glucose tolerance or augment insulin release in this model of pancreatitis-induced diabetes. PMID- 2191458 TI - Effect of a body burn on endotoxin-induced lipid peroxidation: comparison with physiologic and histologic changes. AB - We determined the effect of a 15% total body surface (TBS), full-thickness burn on the physiologic, histologic, and oxidant-induced lipid peroxidation changes produced by endotoxin. The endotoxin-burn response was compared with that of endotoxin alone. Twenty-two adult sheep with chronic lung and flank lymph fistulas were studied. In 11 sheep a burn was produced under anesthesia and 3 days later they were given 2 micrograms/kg of endotoxin. Data were also compared with those of control sheep and those that were given burns alone. Circulating conjugated dienes increased with endotoxin alone but remained at baseline with endotoxin and burn injury. The lung lymph flow response was increased significantly in the endotoxin-burn group (sixfold) compared with that of endotoxin alone (fourfold). Histologic quantitation of lung neutrophil count was comparable in both groups 6 hours after injury, although mononuclear cells were much more evident in lungs in the endotoxin-burn group. Lipid peroxidation measured by malondialdehyde was significantly increased in the endotoxin group compared with the endotoxin-burn group, despite the greater increase in lymph flow and lung water in the burned group. Oxygen consumption (VO2) remained constant after endotoxin alone compared with baseline. However, VO2 increased twofold immediately after endotoxin in the endotoxin-burn group. This marked increase was followed by a significant decrease in VO2 from baseline. Flank soft tissue nonburned increased lung lymph flow twofold to threefold with endotoxin and burn, indicating increased soft-tissue permeability, whereas it remained unchanged with endotoxin alone. Liver malondialdehyde increased from a control of 110 +/- 20 to 210 +/- 80 mmol/gm tissue with endotoxin alone and to 450 +/- 54 nmol/gm tissue with endotoxin and burn. We can conclude that burn injury accentuates both the pulmonary and systemic physiologic response to endotoxin, possibly as a result of mediators released from mononuclear cells already activated in the presence of the burn. The increased lung physiologic response does not appear to be caused by greater oxidant-induced lipid peroxidation, as was seen in the liver with the combined injury. PMID- 2191460 TI - Fetal laser surgery in genetic polydactyly mice. AB - The first digital ray of the hindlimb plate in Slc:ICR mouse fetus was irradiated with 2 watts argon laser beam for 0.3 sec after releasing from the abdominal cavity and envelop of uterine myometrium on day 13 of gestation, and then the fetuses were allowed to develop in the abdominal cavity contacting with the uterus via the placenta exo utero until term. ICR mouse fetuses which received fetal laser surgery lost their first digits completely, resulting in 4-digit hindfoot on day 18 of gestation. The homozygous Polydactyly Nagoya (Pdn/Pdn) mice exhibit 1-3 extra digits both in the fore- and hindlimbs preaxially. The extra digital rays in the left hindlimbs of Pdn/Pdn fetuses were irradiated with 2 watts argon laser beam for 0.3 sec on day 13 of gestation exo utero. The left hindlimbs of the Pdn/Pdn fetuses which received fetal laser surgery lost their preaxial extra digits on day 18 of gestation, resulting in 5 digits, though their 1st digit was triphalangia. The combination of a laser instrument with the fetoscope and/or ultrasound scanner may promote the fetal surgery of congenital anomalies in humans. PMID- 2191459 TI - Ruptured renal artery aneurysm in a pregnant uninephric patient: successful ex vivo repair and autotransplantation. AB - Renal artery aneurysm rupture during pregnancy is a rare event, with only 22 cases recorded in the literature. Maternal and fetal mortality rates have been high, and renal salvage with in situ repair of the renal artery has been documented in only three cases. We present here a case report of renal artery aneurysm rupture in a pregnant patient with congenital absence of the contralateral kidney, which was treated successfully with ex vivo renal artery reconstruction and autotransplantation. The literature on renal artery aneurysm rupture in pregnancy is reviewed and technical aspects of renal artery reconstruction and autotransplantation are presented. PMID- 2191461 TI - [Endocrine orbitopathy--symptoms, diagnosis, therapy]. AB - The diagnosis of graves ophthalmopathy is still essentially an ophthalmological problem, because the etiopathological links to the troubles of the thyroid gland are not yet fully understood. The typical signs and symptoms of the disease, the diagnostic and therapeutic possibilities of the ophthalmologist are described. PMID- 2191462 TI - [Drug side effects on the eye and systemic side effects of medicamentous ophthalmologic therapy]. AB - In part A a brief overview of systemic side effects of ophthalmic drugs such as antibiotics, betablockers, adrenergics, mydriatics and carboanhydrase inhibitors is given. Part B deals with ocular side effects of common drugs such as antibiotics, tuberculostatics, antirheumatics, corticosteroids and phenothiazines. PMID- 2191463 TI - [Automated perimetry]. AB - Today the automated perimetry is worldwide often applied. Beside ophthalmologists, other specialists are increasingly faced with this matter. For this reason some basic aspects are described such as: "differential light sensitivity, "decibel-scale", "strategies", "fluctuations" and so on. Different possibilities to present test results as well as some new features of automated perimetry are described here. PMID- 2191464 TI - [From cataract eyeglasses to the artificial lens--changes in cataract surgery]. AB - After a brief retrospective on the millennia-old technique of luxation of an opaque lens, the radical changes happening in the past 10 to 20 years to cataract surgery are outlined as follows: Microsurgical extracapsular cataract extraction and artificial intracular lens implantation. Some of the consequences for patient and physician are shown, particularly the criteria for undergoing surgery: cataract surgery should be performed whenever the cristalline lens opacities cause marked visual impairment to the patient. PMID- 2191465 TI - [Vitreous body surgery]. AB - A variety of pathological changes of the vitreous endanger the function of the retina and are therefore reason for removement of the vitreous body. The most important technique is the pars plana vitrectomy, which allows to perform the surgical manoeuvre on the stabilized eye. Different indications for vitreoretinal surgery are discussed, as well as materials, which are used for replacement of the vitreous. When long standing replacement of the vitreous is necessary in complicated cases, silicon oil is the most important material. PMID- 2191466 TI - [Use of botulinum toxin in ophthalmology]. AB - Botulinum toxin A injection in essential blepharospasmus and hemifacial spasmus is an important alternative to surgical therapy. The toxin is injected into the lateral parts of the lower and upper lid in single doses of one to two nanograms under electromyographic control. The effect is visible after a few days and lasts for several months. The procedure can be repeated several times. A second important application of botulinum toxin A is strabismus. In paralytic strabismus the contracture of the antagonist of the paralyzed muscle can be weakened by local injection of botulinum toxin by means of a needle electrode under electromyographic control. Thus the contracture of the homolateral antagonist can be overcome and not seldom singular binocular vision obtained again. In cases of moderate pareses which recover spontaneously the muscle weakening effect of the toxin on the antagonist helps to restore binocular single vision. In cases of chronic paralytic strabismus the toxin injection into the antagonist facilitates the surgical intervention on the paralyzed muscle. In concomitant strabismus botulinum toxin A is above all valuable in small angle cases, in sensory strabismus, in cases of over- or undercorrection after surgery, and these especially in adults. In congenital esotropia, in commitant squints with large angles and in chronic or intermittent exotropia surgery is the preferred modality of treatment. The best results are obtained with repeated small doses. Generally a 65% reduction of the strabismus angle after two to three injections can be expected. With injections into the lids and the extraocular muscles no general systemic side effects has been observed. PMID- 2191467 TI - [Non-prostanoid endothelium-derived factors. Physiologic roles and possible implications in cardiovascular pathology]. AB - Non prostanoid endothelium-derived relaxing and contracting factors (EDRF and EDCF, respectively) are released by endothelial cells and act on the underlying vascular smooth muscle. It is now established that EDRF is nitric oxide (NO), whereas EDCF has been recently identified as a 21 residue peptide, called endothelin. However, circumstantial evidence suggests that there may be more than one EDRF and/or EDCF. EDRF (NO) induces relaxation of the underlying vascular smooth muscle by enhancing intracellular level of cyclic guanosine monophosphate. The mechanisms of action of endothelin are still to be defined. It seems however that influx of extracellular calcium may partly account for its action. Although important findings have been made recently, most of the hypotheseses, at our current stage of knowledge, about the respective roles of EDRF and EDCF in disease have still to be proved. However, it is preferable from now to think in terms of balance (or imbalance) between these two factors which, probably, have both a fundamental role and very likely interact with each other in maintaining and regulating vascular tone in man. PMID- 2191468 TI - [Hemodynamic effects of quinacainol administered via an intravenous route. Study in patients with normal left ventricular function]. AB - The haemodynamic effects of a new antiarrhythmic drug quinacainol (RP 54272) were evaluated in 12 untreated patients with normal left ventricular function referred for diagnostic cardiac catheterisation. The haemodynamic data were obtained before, 5 and 25 minutes after the injection of the drug (0.21 mg/kg/min during 6 minutes). A slight decrease of cardiac contractility indexes was constantly observed: dp/dtmax decreased (-15%) in all patients (p less than 0.05), with no concomitant change of left ventricular pressure or left ventricular end diastolic volume with respect to control values. Cardiac output and left ventricular ejection fraction did not change significantly. Heart rate increased in all patients from 74.3 +/- 9.8 to 79.9 +/- 8.6 beats per minute after 5 minutes (paired t test p less than 0.05), and was 79.8 +/- 9.0 beats per minute after 25 minutes. Systemic arterial resistance increased in 7 patients due to a reflex adrenergic discharge. The interpretation of the haemodynamic data was difficult in 3 cases due to systemic vasodilatation, which was poorly tolerated in one patient. The contribution of vagolytic reaction and adrenergic reaction to the negative inotropic effects of the drug must be evaluated before giving in to patients with impaired left ventricular function. PMID- 2191469 TI - [Use of calcium inhibitors in neuropsychiatric pathology]. AB - The use of calcium channel blockers is usual in cardiology today, but seem to spread to others specialties, particularly in the field of neuropsychiatry. The authors report the major clinical studies in neurology (treatment of migraines, epilepsia, dizziness and ischemic stroke) where flunarizine and nimodipine seem to have an important role. In psychiatry, their introduction is more recent. However, some encouraging results have been noted in the treatment of panic disorder, Gilles de la Tourette disease and mania. PMID- 2191470 TI - [Methods for studying the hepatic metabolism of drugs in man]. AB - Various methods can be used to investigate human hepatic drug metabolism in vivo. a) Indirect methods based on the assessment of atoxic substances metabolism in order to investigate: --hepatic oxidative activity by antipyrine or caffeine clearance and aminopyrine breath test determination. Such an activity can be modified by drug-induced enzyme induction or inhibition and in case of hepatic disease; --genetic polymorphism of hepatic drug metabolism assessed by the determination of debrisoquine or dextrometorphane metabolic ratio and of N acetylation phenotype. Unusual therapeutic or adverse effects could be explained by such a polymorphism; --hepatic blood flow, which variations could modify hepatic clearance of drugs with a high hepatic extraction ratio, by the assessment of indocyanine green clearance. b) Direct methods based on pharmacokinetics data and their alterations under various circumstances: simultaneous administration of other drugs, liver disease. PMID- 2191471 TI - The simpliRED D dimer test: a novel assay for the detection of crosslinked fibrin degradation products in whole blood. AB - A new system for the detection of fibrin degradation products in whole blood has been developed. The test provides a clearly visible agglutination of the patient's red blood cells in the presence of elevated levels of the crosslinked fibrin derivative, D dimer. The test, which uses a bispecific reagent prepared from Fab' fragments of monoclonal antibodies, gives a positive result in 1-2 minutes. One monoclonal antibody (RAT-1C3/86) was raised against human red blood cells, and the second (DD-3B6/22) was specific to the crosslinked fibrin derivative, D dimer. Addition of the bispecific reagent to a drop of patient's whole blood resulted in red blood cell agglutination when elevated levels of D dimer were present in the sample. Clinical trials showed sensitivity equivalent to that of current commercial tests. Samples from patients with thrombotic disease states as well as normals were examined. The test was compared with commercial latex agglutination and enzyme immunoassay systems and showed good correlation with the presence of elevated levels of crosslinked fibrin degradation products. This technology represents an advance which allows rapid "on the spot" whole blood analysis, for the diagnosis of thrombotic disorders. PMID- 2191472 TI - Inhibition of platelet aggregation by a whole cell extract from strains of group B streptococcus. AB - A whole cell extract (HCl-Ext) from strains of group B streptococci (GBS) possessing fibrinogen binding activity prevented the platelet aggregation induced with adenosine 5'-diphosphate (ADP), collagen and thrombin, while aggregation by epinephrine and ristocetin was slightly inhibited and arachidonic acid-induced platelet aggregation was not affected whatsoever. When the HCl-Ext was added after commencement of the aggregation, deaggregation was observed in cases induced by ADP, collagen, and thrombin. By precoating the washed platelets with HCl-Ext, both of ADP- and collagen-induced platelet aggregation were suppressed. The active factor in the HCl-Ext seemed to be undialyzable, trypsin-susceptible, and proteinaceous substance, unlike GBS polysaccharide type antigen. PMID- 2191473 TI - Calcium channel blockers reverse the sustained elevation of blood pressure induced by chronic infusion of endothelin in conscious rats. AB - To determine whether endothelin could act as a circulating hormone in the regulation of blood pressure and sodium-water excretion, we assessed the chronic effects of synthetic endothelin on systolic blood pressure, urine volume and urinary sodium excretion in conscious rats, and also evaluated the effects of benidipine or nilvadipine, newly developed calcium channel blockers, in rats infused chronically with synthetic endothelin. Continuous infusion of endothelin at a rate of 60 micrograms/kg/day into the jugular vein via osmotic minipumps induced a significant increase in systolic blood pressure, but did not induce any significant changes in urine volume and urinary sodium excretion, compared to those in vehicle-infused rats. On the contrary, the infusion of endothelin at a rate of 6 micrograms/kg/day did not induce any significant changes in systolic blood pressure, urine volume and urinary sodium excretion, compared to those in vehicle-infused rats. When 6 mg/kg/day of benidipine or 10 mg/kg/day of nilvadipine was administered simultaneously with 60 micrograms/kg/day of endothelin, the systolic blood pressure rose on Day I to only 137.0 +/- 2.4 mmHg (p less than 0.05) and 119.7 +/- 5.9 mmHg (p less than 0.05) compared to the rise to 163.8 +/- 4.7 mmHg when endothelin alone was infused. The antihypertensive effect of benidipine or nilvadipine was sustained for the entire experimental period and was not associated with any significant changes in urine volume and urinary sodium excretion. The present results suggest that endothelin can act as a circulating hormone and might be involved in the regulation of blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2191474 TI - Co-mutagenic activity of phenoxyherbicides MCPA- and MCPB-ethylester in the Ames assay. AB - Mutagenicity and co-mutagenicity of MCPA- and MCPB-ethylester were examined in the Ames assay. It was found that they enhance the mutagenic action of 2 aminoanthracene in the Ames assay, although they were not mutagenic. PMID- 2191475 TI - Acute carbon monoxide poisoning: animal models: a review. AB - Animals have been used for well over a century in an attempt to understand the toxicology, physiology, and pathology of acute carbon monoxide poisoning. Whether the toxic effects of this gas result from primary hypoxia, as in hypoxic hypoxia to which it is frequently compared, or from direct tissue effects since it enters cells and binds to certain vital components, remains a point of controversy. Acute severe poisoning in man and animals affects primarily the cardiovascular and nervous systems, and frequently produces neurologic dysfunction. Morphologically, tissue damage is usually confined to the white matter. The root cause is at best poorly understood and major investigative efforts have been made toward its elucidation. Many studies with rats, cats and primates indicate a major role for CO-induced hypotension, which serves to compromise blood flow and exacerbate acidosis. The likely cellular mechanisms in this process are only now becoming apparent. This review critically examines the recent as well as a few older CO-animal studies. In scope, they fall into several broad categories: general cardiopulmonary effects, metabolic and tissue effects, general resistance (i.e. tolerance), effects on the central nervous system including blood flow, neurochemistry, morphology and behavior, and finally, experimental therapeutic approaches. PMID- 2191476 TI - Fundamental elements of the quality of care: a simple framework. AB - This article argues for attention to a neglected dimension of family planning services--their quality. A framework for assessing quality from the client's perspective is offered, consisting of six parts (choice of methods, information given to clients, technical competence, interpersonal relations, follow-up and continuity mechanisms, and the appropriate constellation of services). The literature is reviewed regarding evidence that improvements in these various dimensions of care result in gains at the individual level; an even scarcer body of literature is reviewed for evidence of gains at the level of program efficiency and impact. A concluding section discusses how to make practical use of the framework and distinguishes three vantage points from which to view quality: the structure of the program, the service-giving process itself, and the outcome of care, particularly with respect to individual knowledge, behavior, and satisfaction with services. PMID- 2191477 TI - [Fibronectin: biologic properties and clinical significance]. PMID- 2191478 TI - [Results of bilio-digestive anastomoses in benign diseases excluding intra hepatic lithiasis]. PMID- 2191479 TI - One hundred years of splenogonadal fusion. PMID- 2191480 TI - Sonographic characteristics of epidermoid cyst of testicle. AB - The ultrasonographic characteristics of an epidermoid cyst of the testicle are presented. Since these findings are similar to other published case reports, preoperative sonographic diagnosis of this lesion may be possible. PMID- 2191481 TI - Localized staging of prostate carcinoma: comparison of transrectal ultrasound and magnetic resonance imaging. AB - To evaluate the usefulness of two new imaging modalities in the clinical staging of prostate cancer the following study was done. Twelve patients with biopsy proved carcinoma of the prostate were evaluated preoperatively with magnetic resonance imaging (MRI) of the pelvis and transrectal ultrasound of the prostate. The main parameters evaluated were the ability of these two modalities to accurately predict capsular penetration and seminal vesicle involvement in these 12 patients: 10 went on to pelvic lymph node dissections, and 8 had radical retropubic prostatectomies. Thus the preoperative studies could be compared to the pathologic results. Based on our results we believe transrectal ultrasonography is more accurate in the assessment of seminal vesicle involvement and comparable to MRI in determining capsular penetration. Because of the lower cost of ultrasound we believe it to be both an economical and accurate way to preoperatively stage prostate carcinoma. PMID- 2191482 TI - Transplantation of horseshoe kidney into single recipient. AB - A case of successful en bloc transplantation of a horseshoe kidney into a single recipient is reported. The literature is briefly reviewed. The use of horseshoe kidneys in transplantation is recommended in selected cases. PMID- 2191484 TI - Life insurance medicine: our heritage. PMID- 2191483 TI - Excerpts from the history of ALIMDA. PMID- 2191485 TI - Thrombolytic therapy in the management of acute myocardial infarction. AB - It is now clear that intravenous thrombolytic therapy is the treatment of choice in selected patients with AMI. It is most effective in patients with their first MIs and of greatest benefit, at least in the short term, for those with large infarctions. It should be given within the first three hours to be most effective and there probably is little benefit for patients after 5-6 hours unless there is evidence of ongoing ischemia. Patients must be selected carefully to reduce the likelihood of serious complications, including intracerebral hemorrhage. There is, as yet, no convincing evidence that early intervention with PTCA or surgery can improve the outcome of patients who have received initial early intravenous thrombolytic therapy when they develop recurrent myocardial ischemia (21,22). The use of rt-PA probably is preferable to the use of streptokinase, but further experience is needed before this can be determined with certainty. The large difference in the cost of these agents will need to be evaluated by the medical community and other health care providers who finally will determine the pattern of use of these and future thrombolytic agents. PMID- 2191486 TI - Exercise and sudden cardiac death: is the run worth the risk? PMID- 2191487 TI - Strategies for risk assessment of ischemic heart disease and total mortality. PMID- 2191488 TI - ALIMDA Research Center report. PMID- 2191489 TI - Immunohistochemical localization of Pasteurella haemolytica A1-derived endotoxin, leukotoxin, and capsular polysaccharide in experimental bovine Pasteurella pneumonia. AB - Six, 5- to 10-week-old male Holstein calves were inoculated intratracheally with 5 x 10(9) logarithmic growth phase Pasteurella haemolytica biotype A serotype 1 (A1). Immunohistochemical techniques in conjunction with the use of monoclonal antibodies directed against P. haemolytica A1-derived lipopolysaccharide (LPS), capsular polysaccharide, and a polyclonal rabbit anti-leukotoxin antibody were used to localize their respective antigens in tissue sections of pneumonic lung at the light and electron microscopic levels. We found the following: 1) LPS, capsular polysaccharide, and leukotoxin were released into the inflammatory exudate; 2) LPS was found within the cytoplasm of neutrophils (located in the alveolus and alveolar wall), alveolar macrophages, endothelial cells, pulmonary intravascular macrophages, and on epithelial cell surfaces; 3) capsular polysaccharide was found in the alveolus and alveolar macrophages but not in cells of the alveolar wall; and 4) leukotoxin was associated with cell membranes of degenerating inflammatory cells located in the alveolus. This is the first study that demonstrates the presence of leukotoxin in the pulmonary inflammatory lesions caused by P. haemolytica A1 and implicates endotoxin as an important factor in the genesis of the pulmonary lesions. PMID- 2191490 TI - Spongy degeneration of white matter in the central nervous system of silver foxes (Vulpes vulpes). AB - A disorder of central nervous white matter in Norwegian-bred silver foxes is described from the case histories of 21 clinically affected foxes. The main presenting sign of this disorder was caudal limb ataxia, which appeared between 2 1/2 and 4 months of age and progressed over the next 4-8 weeks. Only four affected foxes were allowed to live beyond this period, but they showed moderate to marked improvement. Light microscopic examination of specimens from 16 affected foxes necropsied between 3 1/2 and 6 1/2 months of age revealed lesions that were restricted to the white matter of brain and spinal cord. The lesions were characterized by a symmetrical spongy change with vacuoles of varying sizes and included significant myelin deficiency. There was a relative preservation of axons and nerve cells and no significant inflammation or vascular reaction. An astrocytic hypertrophy was usually associated with the spongy change. Ultrastructural examination of central nervous tissue from two, perfusion-fixed, 6-month-old foxes showed intramyelin vacuoles resulting from splitting of the myelin lamellae at the intraperiod line and was interpreted as indicating myelin edema. Expanded extracellular spaces and watery astrocytic processes also contributed to the vacuolar appearance. Astrocytic processes in affected areas were hypertrophic and contained abundant filaments. Although the 16 silver foxes had severe clinical signs, their lesions had features in common with the juvenile form of Canavan's disease in children and a spongy degeneration reported in Labrador Retrievers; however, the clinical course in the foxes was not uniformly progressive. PMID- 2191491 TI - A review of the biochemical roles, toxicity and interactions of zinc, copper and iron: II. Copper. AB - Copper is an essential nutrient for living matter. Through its cuproenzymes, copper displays a variety of metabolic functions. Atomic absorption spectrophotometry, radioisotope studies and establishment of cell and molecular biology have provided the necessary tools to study copper absorption, metabolism, physiology and biochemistry. The vital role of metallothionein in copper homeostasis is examined. Ceruloplasmin represents the molecular link between copper and iron metabolism. The genetic predisposition of copper toxicity has been attributed to the cause of Wilson's disease in humans. The interrelationships between copper and other dietary factors is addressed. PMID- 2191492 TI - FDA poisoning surveillance notes. PMID- 2191493 TI - DNA probes for the detection of toxin genes in Escherichia coli isolated from diarrhoeal disease in cattle and pigs. AB - DNA gene probes specific for genes coding for heat labile toxin (LT), heat stable toxins (STpa, STpb) and Vero-cell toxins (VT1, VT2) were used to examine 1031 diarrhoeal disease isolates of E. coli (345 from cattle and 686 from pigs). Of the bovine strains, 60 hybridized with the STpa probe and most possessed the K99 (F5) or F41 adhesin. Five bovine strains possessed STpb genes and five either VT1 or VT2 genes. Of the porcine strains, 245 hybridized with one or more gene probes. Of 160 K88 (F4) positive strains, 133 possessed both LT and STpb genes, whilst 17 possessed LT or STpb or STpa alone or in combination. Ten K88 strains did not possess toxin genes. Isolates bearing the K99 (F5) adhesion possessed either STpa, STpb and VT2 genes alone or in combination; in one isolate only the LT gene was detected. Isolates belonging to serogroup 0138:K81 were more heterogeneous as to their toxin genes; of the 60 strains, fourteen carried only VT2 genes, thirty-two carried VT2, STpa and STpb genes, one carried LT, VT2, STpa and STpb genes, two carried STpb gene, four carried STpa and STpb genes, one carried LT and VT2 genes, two carried LT and STpa genes, whilst four carried none. Twenty-four percent of all toxigenic strains apparently did not possess adhesins. PMID- 2191494 TI - Interference patterns of human immunodeficiency viruses HIV-1 and HIV-2. AB - The ability of cells infected with a retrovirus to interfere with superinfection by another retrovirus usually involves blockage, by the primary virus, of the receptors for the superinfecting virus. Retroviruses using different receptors do not interfere with each other, and this property has been used to classify various types of retroviruses. Different isolates of human immunodeficiency virus (HIV) were subjected to this type of analysis, and it was found that all HIV-1s cross-interfere with each other in T cells as well as in U937 promonocytic cells, substantiating further that all isolates use the same receptor on these cells. An HIV-2 isolate was found to interfere with HIV-1s, but HIV-1s only partially interfered with HIV-2 superinfection, indicating that inherent differences in receptor interactions exist between HIV-1s and HIV-2. For comparison, interference patterns of D-type primate retroviruses (SRVs) and murine amphotropic and xenotropic retroviruses revealed that each virus fell within distinct interference groups demonstrating that human T cells possess at least four distinct receptors for retroviruses. The mechanism of HIV interference was found to be due to receptor blockage in productively infected cells and to receptor elimination in latently infected T cells. Our findings that all HIV-1s completely interfere with each other and that interference occurs rapidly following acute infection suggests that a cell infected with HIV-1 will not permit reinfection by progeny or by other exogenous HIVs. This, in turn, suggests that progeny reinfection may not be the source of the large amount of unintegrated viral DNA observed following HIV cytopathic infection. PMID- 2191495 TI - Nonsense mutants defining seven new genes of the lipid-containing bacteriophage PR4. AB - Thirty-eight new nonsense mutants of the lipid-containing bacteriophage PR4 were isolated. These mutants define seven new viral genes, including the gene encoding the terminal genome protein and an accessory lytic factor. The defective gene products produced in uv-irradiated cells infected with representative mutants from each of the new genetic groups were identified using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Extracts of uv-irradiated cells infected with nonsense mutants that produce a defective major capsid protein, P2, also lacked two lower molecular weight proteins. The synthesis of all three protein species was recovered in cells infected with one-step revertants of two independent major capsid protein mutants, suggesting the possibility of post translational processing or overlapping genes. The time course of protein synthesis in wild-type PR4-infected cells was examined using SDS-PAGE. These analyses revealed at least 34 proteins produced following phage PR4 infection that were not present in uninfected control cultures. PMID- 2191496 TI - A physical-genetic map of the lipid-containing bacteriophage PR4. AB - A physical map of the bacteriophage PR4 genome was constructed which includes 59 sites for 10 restriction endonucleases. The average size of the phage PR4 genome estimated from the sum of DNA fragments generated with the restriction endonucleases Hphl, Mnll, Bgll, AlwNl, and BstXl is 15,170 +/- 240 bp. A collection of recombinant plasmids containing restriction fragments of PR4 DNA generated with Bgll, Hphl, Mnll, and Xmnl inserted into either the low copy number plasmid vector pHSG575 or the high copy number plasmid vector pUC19 was constructed. This collection of recombinant plasmids represents roughly 93% of the PR4 genome. We also constructed a bank of 136 recombinant plasmids containing PR4 DNA fragments resulting from Hpall partial digestion. We have localized 13 genes on the phage PR4 genome through marker rescue with these phage DNA clones. These genes include the structural genes for the major capsid protein (P2) and a nonstructural protein (P6A) implicated in virus assembly. PMID- 2191497 TI - Inducible gene expression from vaccinia virus vectors. AB - A system for inducible gene expression by vaccinia virus (VV) vectors utilizing the Escherichia coli lac I repressor/operator system is described. A VV recombinant that expresses the lac I repressor protein from the constitutively active 7.5K promoter was constructed. Gel retardation experiments showed that a protein present in extracts of cells infected with this virus, but not wild-type virus, bound to the lac operator and that this binding was inhibited by IPTG. A series of VV recombinants were constructed that contained a 21-bp synthetic operator sequence(s) at different positions between the VV late 4b promoter and the firefly luciferase gene. Cells were co-infected with one of these viruses and the VV recombinant expressing the lac I repressor protein in the presence or absence of IPTG, and the level of luciferase activity was determined. Single operators positioned 19, 11, or 6 bp downstream of the promoter resulted in the 30, 50, or 97% inhibition of luciferase activity, respectively, while two operators increased the inhibition to greater than 99.9%. Addition of 1.25 mM IPTG at any time after infection restored 90% of enzyme activity from viruses containing a single operator, but reversal was only 50% when two operators were present. Both elements of the lac I inducible system were functional and stable in the genome of single recombinant virus. S1 nuclease protection of virus mRNA confirmed that luciferase expression was controlled at the transcriptional level and that IPTG did not affect transcription of endogenous VV genes. The utility of this inducible expression system for functional analyses of endogenous VV genes is demonstrated by the controlled expression of a gene encoding a 14-kDa protein and the correlation of 14-kDa expression with a biological property of the virus, namely plaque size phenotype. Plasmid vectors that are generally applicable to the inducible expression of genes by VV recombinants are described. PMID- 2191498 TI - The proteinase polypeptide of adenovirus serotype 2 virions. AB - The Ad2 proteinase, which is thought to be encoded by a 23-kDa open reading frame located at the end of the L3 family of late mRNAs, is expressed poorly even late after infection. To obtain sufficient proteinase for biochemical characterization, a DNA fragment containing the 23-kDa open reading frame was cloned into plasmids that permit efficient expression in Escherichia coli. Polyclonal antiserum specific for the Ad2 proteinase was produced by immunizing rabbits with a fusion protein that included the entire proteinase open reading frame, and this antiserum was used to show that the product of the 23-kDa reading frame is assembled into virions. Bacterial products corresponding to the complete 204 amino acid proteinase reading frame, to a 9 amino acid proteinase deletion, and to a proteinase fusion protein of 227 amino acids were used to determine the size of the proteinase polypeptide in Ad2 virions and in infected HeLa cell extracts. A single proteinase polypeptide that migrated during SDS-polyacrylamide gel electrophoresis with the 204 amino acid recombinant proteinase was detected in wild-type and H2ts1 virions, and in infected cell extracts. Immunoblot titrations showed that a wild-type Ad2 virus particle contains about 10 proteinase polypeptides; an H2ts1 virion has approximately fivefold less proteinase. In virions, the proteinase was associated primarily with the virus core. The 204 amino acid proteinase produced in E. coli permitted cleavage of the major core protein precursor, P-VII, to mature, authentic VII, but the proteinase deletion lacking 9 amino acids from near the amino-terminus was inactive. These results are inconsistent with autocatalytic processing of the Ad2 proteinase as was reported by Chatterjee and Flint (1987, Proc. Natl. Acad. Sci. USA 84, 714 718). PMID- 2191499 TI - Comparison of the positions and efficiency of cleavage activation of fusion protein precursors of virulent and avirulent strains of Newcastle disease virus: insights into the specificities of activating proteases. AB - The F1- and F2-polypeptide components of in ovo activated fusion proteins of one virulent (AV or Australia-Victoria) strain, one low-virulence (EG or Eaves Grimes) strain, and two avirulent (V4 or Queensland and WA2116) strains of Newcastle disease virus (NDV) were isolated and subjected to structural analysis. This included complementary application of amino acid analysis, fast atom bombardment-mass spectrometry, and N-terminal sequence analysis to fragments isolated from AspN protease digests of the F2-polypeptides using HPLC. As a result, the complete sequences of the F2-polypeptides were determined, including documentation of glycosylation of asparagine 54. The sequence of the cleavage activation site of the WA2116 F0-protein was found to be distinctly different from this site in any other NDV F0-protein. Cleavage activation at the C termini of the F2-polypeptide regions was found to have occurred to approximately equivalent extents at arginines 82 and 85 of the AV and EG strains, but was restricted largely to arginine 85 of the V4 strain and completely to arginine 85 of the WA2116 strain. In each case cleavage activation was apparently succeeded by trimming of the basic residues from the newly formed C termini. Immunochemical analysis with antipeptide antisera showed that the extent of cleavage was influenced by amino acids adjacent to these arginines. These data provide insight into the substrate specificities of the enzymes involved in cleavage activation of the fusion protein precursors. PMID- 2191500 TI - Transcriptional activation of the human immunodeficiency virus type 1 long terminal repeat by hepatitis B virus X-protein requires de novo protein synthesis. AB - Human hepatitis B virus (HBV) X-gene, previously shown to be capable of trans activating heterologous regulatory elements of the human beta-interferon gene, the human immunodeficiency virus type I (HIV-1) long terminal repeat (LTR), the simian virus 40 (SV40), and HBV, has the capacity to code for a 17-kDa polypeptide (designated pX17). We now report that pX17 synthesized in Escherichia coli can activate transcription controlled by the HIV-1 LTR using a protoplast fusion technique. Protoplasts of E. coli-containing presynthesized X-protein were fused with lymphocytic H938 cells harboring an integrated copy of a plasmid with the CAT gene under control of the HIV-1 LTR (HIV-1 LTR CAT) and a marked increase in the steady state expression of the CAT mRNA was observed. When the same fused cells were treated with the protein synthesis inhibitor cyclohexamide, the pX17 dependent activation of the HIV-1 LTR was abolished. This result indicates that the X-protein expressed in E. coli is biologically active and suggests that the HBV X-protein-mediated trans-activation of the HIV-1 LTR in this system requires de novo cellular protein synthesis. PMID- 2191501 TI - [Transcranial Doppler measurement of hemodynamics in the major cerebral arteries]. AB - Using a pulsed Doppler velocity meter, the authors assessed by a transcranial approach, in order to obtain an idea on the normal haemodynamics of the basal cerebral arteries, the maximal systolic blood flow (Vmax., m.s-1) in these arteries in a group of 25 healthy young men and in 20 healthy children. In different arteries of the two groups the following mean values of Vmax. were recorded: middle cerebral artery 0.73 +/- 0.11 parallel 0.80 +/- 0.17 m.s-1; anterior cerebral artery 0.55 +/- 0.06 parallel 0.51 +/- 0.09 m.s-1 and posterior cerebral artery 0.44 +/- 0.04 parallel 0.40 +/- 0.02 m.s-1. The assessed values of Vmax. are in agreement with data of other authors. Using the transcranial Doppler method (TD), the authors recorded in 10 children examined in the acute and subsequent stage of cerebrovascular disease recanalization of original occlusions in the anterior, middle and posterior cerebral arteries in the carotid siphon and in the basal artery and improved cerebral haemodynamics in A-V malformation in the basal ganglia. The TD method thus makes it possible to diagnose and follow up the course of these diseases. To illustrate the assessment of the function of the circle of Willis we made in three of our followed up patients with stenosis of extracranial internal carotid arteries static compression tests of both common carotid arteries. The TD method makes it possible to follow up the course of haemodynamic changes in diseases of the cerebral arteries and along with the angiographic examination it extends and supplements the evaluation of the pathological condition of the cerebral arteries and its extent. PMID- 2191503 TI - High-dose epinephrine therapy and other advances in treating cardiac arrest. AB - These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from transcriptions, they are prepared by Homer A. Boushey, MD, Professor of Medicine, and Nathan M. Bass, MD, PhD, Associate Professor of Medicine, under the direction of Lloyd H. Smith, Jr, MD, Professor of Medicine and Associate Dean in the School of Medicine. Requests for reprints should be sent to the Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA 94143. PMID- 2191504 TI - [Contribution of genetics to research in the etiology of depressive diseases]. AB - The familial aggregation of depressive disorders is a major cue for the etiology of depression. The review of family, twin, adoption and linkage studies demonstrates that genetic transmission is involved in the manifestation of bipolar affective disorders but it explains only part of the variance; the evidence of a genetic basis of unipolar depression is less clear; this is the case for endogenous depression, too. It ist recommended to examine if personality features may contribute to an improvement in the identification of the phenotype in genetic studies in unipolar and bipolar depression. PMID- 2191505 TI - [Aspects of time--its distortions in psychiatric diseases]. PMID- 2191506 TI - [Cardiac positron emission tomography--current status and future perspectives]. AB - Positron emission tomography (PET) permits the non-invasive examination of myocardial metabolism. At present, combined imaging of myocardial blood flow and glucose metabolism are used to distinguish viable myocardium from scar tissue, which is particularly important for deciding on therapeutic interventions. In the future, further indications for PET imaging are foreseeable, with refined imaging techniques and development of new tracer substances. Tracers for assessment of adrenergic and muscarinic myocardial receptor density, as well as new positive markers of myocardial ischemia are currently being explored. Labeled amino acids are being employed for assessment of protein metabolism. Finally, C-11 acetate as a tracer of tricarboxylic acid cycle activity and myocardial oxygen consumption has been suggested for clinical use in initial studies in man. PMID- 2191508 TI - [Nurses' history--from nice girl to fighting agitator]. PMID- 2191507 TI - [The effect of intravenous nifedipine administration on coronary occlusion during coronary angioplasty on ischemia tolerance and collateral function]. AB - In 29 consecutive patients (pts) coronary wedge pressure (CWP) was determined as an indicator of coronary collateral function during coronary angioplasty. Collaterals to the target vessel were angiographically detectable in 21 pts. CPW, aortic pressure (AOP), pulmonary wedge pressure (PCP), intervals to appearance of angina pectoris, surface and intracoronary ECG-changes were registered during two (n = 10) or three (n = 19) consecutive balloon dilatations. A total of 21 pts received 0.8-1.0 mg nifedipine intravenously before a second or third dilatation was performed; a control group (n = 8) received placebo. Hemodynamic parameters were reproducible for all dilatations without nifedipine. After administration of nifedipine significant changes occurred: decreases of CPW (from 34 to 29 mm Hg), AOP (from 121 to 110 mmHg), and PCP (from 12.4 to 9.4 mm Hg), and increase of ischemic tolerance time (angina pectoris) (from 35 to 56 s) (p less than 0.01). Changes in CWP and AOP showed a statistical tendency to correlate (p = 10). Thus, intravenous administration of nifedipine can improve ischemic tolerance during coronary angioplasty. Simultaneous measurement of coronary wedge pressure could not prove enhancement of collateral function as being responsible for these antiischemic effects. PMID- 2191509 TI - [Schistosoma species in Senegal with special reference to the biology, epidemiology and pathology of Schistosoma curassoni Brumpt, 1931]. AB - By combining field and experimental investigations, we were able to study several new aspects of fundamental problems concerning human and animal schistosomiasis in Senegal. Because of the controversy about the identity of Schistosoma curassoni and the possibly connected zoonosis, this parasite has been described once more. A great variety of experimental techniques were used. The eggs of S. curassoni are significantly smaller than those of the two other African species of Schistosoma we know of in ruminants (S. bovis and S. mattheei). But eggs of S. curassoni cannot be distinguished from those of the human, pathogenic S. haematobium. The study of the tegument of adult male worms shows a clear difference between S. bovis on one hand, and S. curassoni and S. haematobium on the other hand. S. bovis' tubercles are well formed, but have no stings at all. The tubercles of S. haematobium and of S. curassoni definitely possess stings. S. curassoni, S. haematobium and S. bovis are also clearly different as to their development in hamsters (Mesocricetus auratus). S. curassoni develops more rapidly and gets bigger than S. bovis and S. haematobium. Finally, different enzymatic systems allow us to distinguish S. curassoni from other schistosoma's of the haematobium group. S. curassoni has a typical pattern for phosphoglucomutase and hexokinase, differing from S. haematobium's patterns. In S. bovis, it differs by the patterns of phosphoglucomutase, glucosephosphate isomerase, hexokinase and acid phosphatase. Epidemiological studies proved that, in Senegal, Bulinus guernei is the main vector of S. bovis, Bulinus senegalensis of S. haematobium (Northern Senegal) and Bulinus umbilicatus of S. curassoni and S. haematobium (Southern Senegal). There is no indication to consider S. curassoni as a zoonosis. When ruminants are infested by S. curassoni, the symptoms are light and the most important lesions can be found in the liver, the intestines and, in a lesser degree, in the bladder. S. curassoni develops easily in laboratory animals, giving severe lesions in liver and bowels. That makes it an interesting new model for studying the pathogenesis of schistosomes of the haematobium group and the action of new anthelmintics to be used against them. PMID- 2191510 TI - [Neuropsychological observations and clinical neurology]. AB - The term "neuropsychology" covers the study of the higher functions of man with respect to the structure and the functional organisation of the nervous system, and therefore clearly belongs to the neurological sciences. The nervous system forms a whole, composed of innumerable integrating mechanisms, ordered into a hierarchy of levels ranging from the most elementary activities, which are the most genetically determined and the most permanent, to the activities that are predominantly acquired, which are the most mobile and the most reversible ones. All parts of the nervous system--ranging from the simplest to the most complex- contain reflecting cycles, which maintain themselves in relationships of mutual dependence. The impairment of one or other activity does not mean that the function resides in the damaged part of the nervous system, but merely implies that this part is essential for its completion. The perception of an agnosia patient, the locomotor system in the case of disturbed apraxia, the reactions of a patient with disturbances in the state of consciousness, the mental capacities of a demented person, all these are the result of the global activity of a nervous system which has been depleted of certain capacities and which is curbed by new limitations. In the infinite tangle of the cerebral system, the lesion cancels one or more links which fulfil a physiological role. Depending on where the broken link is situated, the remaining functional organisation coming to the surface in this way expresses itself in a pattern of behaviour which is not strictly related. According to the principle introduced by Jackson, the lesion eliminates certain activities, and releases others, which integrate themselves into underlying levels. In this way the activities of the nervous system regress according to the opposite direction of the hierarchic evolution of their structure: from the most complex to the simplest, from the most propositional to the most automatic, from the least to the most organised.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2191502 TI - Current status of renal transplantation. AB - The success rate of renal transplantation has improved considerably during the past decade, with substantial improvements in both graft and patient survival. The quality of graft function, however, and not graft survival alone is increasingly determining the standards by which transplantation outcome is being judged. As the demand for kidney transplants continues to rise and transplants are being offered to an ever-increasing number of patients, organs are being sought from new supply pools and efforts are being made to use current resources more efficiently. Improvements in clinical management have allowed short-term complications such as infection and rejection to be better prevented or better diagnosed and treated. Fundamental advances in the understanding of the immunologic processes underlying both allograft rejection and acceptance and the introduction of new immunosuppressive agents have allowed a better use of drug therapy and have moved the goal of acquired transplant tolerance closer to attainment. With improved initial transplant success rates, the long-term transplantation outcome is becoming more important. The role of tissue matching in preventing chronic rejection is becoming more appreciated, and the long-term risks of malignancy, arteriosclerosis, and chronic rejection are being better recognized and managed. PMID- 2191511 TI - [Methods of regional analgesia in closed trauma of the chest]. AB - The literature data has been analysed to evaluate the efficacy of the methods of regional analgesia (RA) in closed chest trauma. Various types of blocks are described. Epidural analgesia with local anaesthetics and narcotics is detailed. Epidural electrostimulation and introduction of drugs affecting the endogenous systems are shown to show good promises. PMID- 2191512 TI - [The clinical use of immunosorption: problems and perspectives]. AB - The data concerning clinical use of extracorporeal immunoadsorption are summarized. At present, broad use of this therapeutic approach is hampered by several technological and medical problems such as incomplete biocompatibility of carrier, pyrogenic reactions, ligand "leakage" and rebound phenomena. However, the technology of ex vivo removal is much more developed, than the fundamental knowledge of relevant target substance to be removed in specific clinical situation. The appropriate denomination of such "targets" should provide this method with a wide application field in clinical medicine. PMID- 2191513 TI - [The use of capoten in the treatment of chronic cor pulmonale in elderly patients]. AB - Forty patients of elderly and senile ages with chronic obstructive bronchitis, complicated with degrees II-III respiratory insufficiency, and chronic cor pulmonale with stage IIA circulatory failure have been examined. The examination revealed impairment of the external respiration and tissue oxygen exchange, changes in the cardio- and hemodynamics the most typical of which was a significant rise of the diastolic volume of the left ventricle, activation of the renin-angiotensin-aldosterone system, and an increase of the extracellular volume of fluid. To explore the ways to correct these changes, nine patients were given a single dose of capoten, an inhibitor of the converting enzyme angiotensin (12.5 mg orally), after which a 20-day course was administered (12.5 mg three times daily). The agent proved to be highly effective, which suggested the expediency of its use in the complex management of old-age patients with decompensated cor pulmonale. PMID- 2191515 TI - [Current views on the etiology and pathogenesis of peptic ulcer]. PMID- 2191514 TI - [The possible role of glucocorticoid hormones in the aging of the body]. PMID- 2191516 TI - [The bioenergetic mechanisms of homeothermy]. AB - A number of experiments on isolated muscles and animals allowed to conclude that the amount of energetic expenditures and heat production per 1 unit of muscular work (or power) was not a biological constant as proposed by A. Hill. This value can be changed in the organism, and this allows to increase heat production and homoiotermy in certain environment. The work/heat production ratio was shown to be regulated for all kinds of biological work in organism. The data obtained and the calculations change our notions of energetics and of principles of homoiothermy. PMID- 2191517 TI - [Psychoanalysis]. PMID- 2191519 TI - [Recent developments in group psychotherapy]. PMID- 2191518 TI - [Dynamic psychotherapy]. PMID- 2191520 TI - [Behavior therapy]. PMID- 2191521 TI - [Family therapy--recent developments and outlook]. PMID- 2191522 TI - [Hypnosis and relaxation technics]. PMID- 2191523 TI - [Music therapy, art therapy, body-centered treatment procedures]. PMID- 2191524 TI - [Inpatient psychotherapy]. PMID- 2191525 TI - [Psychotherapy in psychiatry]. PMID- 2191526 TI - [Psychotherapy in the clinical consultation and liaison service]. PMID- 2191527 TI - [Institutionalized services and counseling resources]. PMID- 2191528 TI - [Scientific evaluation of psychotherapy]. PMID- 2191530 TI - [Better chances in male subfertility?]. PMID- 2191529 TI - A cucumber mount for the preparation of histological sections of the small intestine of rodents. AB - A method for orientation of formaldehyde-fixed intestinal tissue from mink puppies (Mustela vision) is described. Sections of the intestine were glued to dehydrated slices of cucumber (Cucumis sativus L. or Cucurbita pepo L.) with egg albumin. This cucumber-intestine unit was processed in a routine way. Embedding in paraplast was facilitated thereby ensuring a correct orientation of the tissue. PMID- 2191531 TI - [Epidemiology of breast cancer]. AB - Leading position and further increase in breast cancer incidence in many countries are the most important facts of the descriptive epidemiology of breast cancer. In the GDR breast cancer incidence amounts to 60 per 100,000 per year. There are large differences in the incidence between populations, which support hypotheses about the life style, especially of diet, as a risk factor for breast cancer. Early age at menarche and late menopause, nulliparity and late age at first birth, breast cancer in first-degree relatives, benign breast disease and radiation increase breast cancer risk. Intake of oral contraceptives does not alter the overall risk for breast cancer. However, there are different results concerning the use in young age and before first full term pregnancy. Case control studies concerning diet are not yet convincing. The results are discussed with respect to beneficial activities in controlling breast cancer. PMID- 2191532 TI - [Congenital cystic adenomatoid malformation of the lung in a fetus]. AB - Occasionally the intrauterine ultrasonography routinely done in the 21st gestational week pronoinced fetal ascites and intrathoracic tumour have been visualized. Spontaneous abortion of a male fetus in the 22nd gestational week. In necropsy the solid form of congenital cystic adenomatoid malformation of the whole right lung could be diagnosed. PMID- 2191533 TI - Structural features of the LH/CG receptor. PMID- 2191534 TI - [Cytologic molecular detection of oncogene expression: possibilities and prospects in hemato-oncology]. AB - Proto-oncogenes, the normal equivalents to the transforming genes of mammalian tumorigenic retroviruses, are implicated in essential biological processes of normal human cells, like differentiation and proliferation. In vivo and in vitro studies clearly demonstrate that activation of proto-oncogenes with subsequent transformation in tumorigenic oncogenes plays an important role in induction and acceleration of the malignant disease, and also determines metastatic spread and development of resistance to chemotherapy in certain neoplasias. Investigation of these genes and analysis of their activation state should routinely be introduced in staging of hematological neoplasias, thus contributing to refinement of histopathological classification, clearer discrimination between reactive and neoplastic conditions and understanding of pathophysiological processes. Furthermore, impact on definition of high risk patients and novel therapeutic concepts based on a better definition of tumour biology may be expected from these studies. "Molecular cytology" combines detection of oncogenetic mRNA and the relevant oncoprotein on the single cell level by using "mRNA-in situ hybridization" and immuno-histochemistry. Application of this technique will allow to determine the mechanisms regulating the expression of oncogenes to define functional heterogeneity of tumour cell subsets and to clarify the relevance of minimal residual disease. PMID- 2191535 TI - Patency and flow velocity profiles in the internal carotid artery assessed by digital subtraction angiography and Doppler studies two years after endarterectomy. AB - A follow-up of 55 patients 2 years after a total of 60 carotid endarterectomies. Fifty-two patients who had a total of 57 endarterectomies survived the first 2 post-operative years and were re-examined using pulsed Doppler spectral analysis and intravenous digital subtraction angiography (IVDSA). One patient had died following a stroke and 2 after a cardiac infarction. The Doppler and IVDSA examinations revealed a non-symptomatic restenosis of the relevant internal carotid artery in 2 patients. There were no relevant occlusions and no symptomatic re-stenoses were detected. Spectral spreading of the Doppler signal at the site of the endarterectomy was found in 18% of the internal carotid arteries, whereas wall irregularities (diameter reduction less than 10%) were demonstrated in 25% by IVDSA. A stenosis or occlusion was found in 14 (25%) of the 57 ipsilateral external carotid arteries. PMID- 2191536 TI - Idiopathic palatal myoclonus. AB - Two cases with idiopathic palatal myoclonus without other neurological deficits were described. They did not have any other neurological deficits other than myoclonus of branchial muscles. In these cases, the myoclonus disappeared during natural or induced sleep. In Case 1, the myoclonus ceased transiently when the patient was calculating or receiving an injection. In Case 2, the myoclonus disappeared with intravenous injection of saline as a placebo. Detailed examinations, including brain CT, MRI and multiple evoked potentials, showed normal results. The myoclonus in Case 2 disappeared after we had explained that her disease was benign. Since the clinical features and laboratory data in idiopathic palatal myoclonus are quite different from those in palatal myoclonus with other neurological deficits, idiopathic palatal myoclonus is considered to be a separate syndrome. Invasive examinations or excessive medications should be avoided because of its benign prognosis. PMID- 2191538 TI - Chromogranin A: osmotically active fragments and their susceptibility to proteolysis during lysis of the bovine chromaffin granules. AB - Osmotically active fragments of chromogranin A (Chr A) were studied in lysates from bovine chromaffin granules (CG) disrupted in the presence or absence of inhibitors of endogenous proteolytic activities. The effects of various methods of lysis were examined by micro-osmometry, PAGE-SDS electrophoretic techniques and immunoblots with polyclonal anti-Chr A sera. Osmotically active 'small' Chr A fragments (below 30 kDa) were conspicuous in lysates containing cocktails of leupeptin, pepstatin A, pHMB, PMSF and aprotinin. The osmotically inactive native Chr A in the 68-100 kDa range and the osmotically active fragments below 47 kDa were degraded in lysates at neutral or acid pH in the absence of inhibitors. However, degradation of the native Chr A and intermediates below 47 kDa could be prevented by extraction directly from intact CG, notably in cold or boiling distilled water. On the other hand, the main product after large-scale extraction of CG in 1 M acetic acid (pH 1.9, 100 degrees C) was a novel, osmotically active fragment (22 kDa), immunostaining only for the N-terminal sequence (Chr A1-40). The heat-stable fraction (Mr,n 23 kDa) exhibited concentration-independent colloid osmotic pressures even in the absence of phosphate, a property which may distinguish this N-terminal-containing fragment from the larger intermediates, probably containing the pancreastatin sequence, and other regions at the C terminal side of the prohormone molecule. The functional roles of these osmotically active intermediates in the processing of Chr A are not yet known. PMID- 2191537 TI - Occurrence and effects of endothelin in guinea-pig cardiopulmonary tissue. AB - Endothelin-like immunoreactivity (-LI) was present in the guinea-pig cardiopulmonary tissues with the associated autonomic neural supply. The highest levels were found in the stellate ganglion (15 pmol g-1) followed by the vagus nerve, pulmonary artery, lung and right atrium of the guinea-pig. Endothelin I, but not endothelin III, induced an increase in contractile force and frequency followed by an atropine-resistant inhibition of right atrial contractility at higher concentrations. Exposure to endothelin I caused a pronounced, long-lasting coronary vasoconstriction as revealed by a decrease in perfusate outflow. In addition, both heart and contractile force were attenuated. Guinea-pig bronchi in vitro contracted upon exposure to endothelin I and III, but only endothelin I caused contraction of pulmonary arteries. The C-terminal hexapeptide of endothelin I did not influence right atrial, bronchial or pulmonary artery contractility. Endothelin I increased the mean arterial pressure and insufflation pressure and decreased the heart rate in the guinea-pig in vivo. In conclusion, endothelin-LI is present in the cardiovascular, respiratory and nervous tissues of the guinea-pig and endothelin induces strong coronary and pulmonary vasoconstrictor effects. The effects on atrial contractile force and frequency are concentration-dependent with stimulation at lower and inhibition at higher concentrations. Based on the diversity in response to endothelin III in the bronchi compared to atrium and pulmonary artery, it may be suggested that different receptor populations exist in bronchial and cardiovascular muscle, although the cellular localization and forms of endothelin present in guinea-pig cardiopulmonary tissue remain to be established. PMID- 2191539 TI - Variations of ultrasonic anatomy of the hepatic veins within the human liver. AB - The aim of this study was to investigate various physiological variations of the hepatic veins within the liver of the 60 healthy subjects. All participants required physical examinations, different laboratory tests and upper abdominal ultrasonogram--all completely normal. Demonstration of the hepatic veins have been performed on sector real-time systems. The results clearly demonstrated that the physiological variations of the hepatic veins are very common. Ultrasonography obviously represents a diagnostic method of choice in the evaluation of anatomy of the hepatic venous system. PMID- 2191540 TI - Conventional B-mode and transvaginal color Doppler in ultrasound assessment of ectopic pregnancy. AB - The study was arranged in two parts. In the first part, 43 of the clinically suspected ectopic pregnancies were sent for a transvaginal color Doppler examination. Both cystic and complex adnexal masses were carefully scanned for their Doppler flow characteristics. The Pourcelot index (RI) was calculated and the RI 0.40 was used as a cut-off point to differentiate the trophoblastic (RI less than 0.40) and the normal blood flow (RI greater than 0.40). The diagnosis was confirmed by the beta hCG serum test. Three false-negative and one false positive findings were obtained. The transvaginal color and pulsed Doppler study of the flow within ectopic pregnancy has a high degree of sensitivity (87.5%), specificity (94.7%) and accuracy (90.7%). Pelvic sonograms of another 110 patients with proven ectopic pregnancy were reviewed retrospectively. The ectopic gestational sac with the alive embryo was documented in 11.8% cases and without the embryo in 30.4% cases. A mixed, solid or cystic adnexal mass was detected in 57.8% patients. Intrauterine findings showed a pseudogestational sac in 13.6% cases, a cluster configuration in 18.6% cases and a linear configuration in 67.8% cases. Criteria for the ultrasound diagnosis of ectopic pregnancy influencing its specificity, sensitivity and accuracy are discussed. PMID- 2191541 TI - Rapid methods in clinical microbiology. Present status and future trends. PMID- 2191542 TI - "Where we've been and where we may be going". PMID- 2191543 TI - Time-resolved fluorometry: principles and application to clinical microbiology and DNA probe technology. PMID- 2191544 TI - The influence of rapid diagnosis of streptococcal infection on pharyngitis and rheumatic fever. PMID- 2191545 TI - Use of DNA probes for the diagnosis of infections caused by Mycoplasma pneumoniae and legionellae--a review. AB - Specific DNA probes have been made for both M. pneumoniae and Legionella species. Dot blot methods have been used in research laboratories to test culture isolates of both organisms, and also to test animal tissues with a L. pneumophila-specific probe. Commercial kits are also available for direct specimen testing for these two organisms. The commercial kits are made by a single manufacturer, Gen-Probe, Inc. (San Diego, CA), and use a novel in-solution rapid hybridization assay, using 125I-labeled cDNA to rRNAs of the organisms. The Gen-Probe M. pneumoniae probe appears to be 80% to 100% sensitive, and 97% to 100% specific, based on analysis of two clinical studies using positive culture as the diagnostic criterion. The Gen-Probe legionella probe appears to be 33% to 71% sensitive (mean 57%), and 98.9% to 99.7% specific (mean 99.7%), based on analysis of four prospective clinical studies, using positive culture as the definition of disease, with a total sample size of 3,243 patients, 49 of which were culture positive. Both Gen-Probe direct tests appear to be clinically useful, although the poor performance of the legionella test in one major university laboratory, and the expense of performing these tests, mandate that thorough evaluations be carried out in each laboratory anticipating using the test. Culture must always be performed for legionella whether or not the DNA probe test is used. It is likely that the use of the M. pneumoniae kit would greatly speed diagnosis, but whether this would alter medical practice or result in lower morbidity and health care costs is unknown. PMID- 2191546 TI - Non-culture tests for the diagnosis of gonorrhea. PMID- 2191547 TI - S-100 proteins: relationships with membranes and the cytoskeleton. PMID- 2191548 TI - Oncomodulin in normal and transformed cells. PMID- 2191549 TI - High levels of oncomodulin and calmodulin expression in the log phase of cell growth in a chemically transformed rat fibroblast cell line. PMID- 2191550 TI - Calmodulin and calbindin in pancreatic islet cells. AB - The process of insulin release evoked by D-glucose and other nutrient secretagogues is triggered by an increase in cytosolic Ca2+ activity. However, some other insulinotropic agents may stimulate insulin release at a close-to basal concentration of cytosolic ionized calcium. The control of cytosolic Ca2+ concentration depends not solely on the rate of Ca2+ entry into the cell through voltage-sensitive channels and Ca2+ exit via Na(+)-Ca2+ countertransport or active Ca2+ pumping, but also on the subcellular distribution of Ca2+, as dependent, for instance, on both Ca2(+)-ATPase activity and inositol 1,4,5 triphosphate-sensitive release in microsomes and calcium accumulation in mitochondria. Calmodulin and calbindin were both identified in pancreatic islet cells. Activation of adenylate cyclase by calcium-calmodulin may account for the increased production of cyclic AMP in islets stimulated by nutrient secretagogues. Calbindin is present in both normal and tumoral islet cells, and might participate to the alteration of islet function encountered in vitamin D deprived or repleted rats. However, no target enzyme for calbindin was yet identified in islet cells. Independently of the role of calcium-binding regulatory proteins, the mitochondrial accumulation of calcium may account in part at least, for the preferential stimulation of mitochondrial oxidative events in the process of nutrient-stimulated insulin release. PMID- 2191551 TI - Possible role for two calcium-binding proteins of the S-100 family, co-expressed in granulocytes and certain epithelia. PMID- 2191552 TI - Phosphorylation of the calcium-binding protein, p68, in the submembranous cytoskeleton of human placental syncytiotrophoblast. PMID- 2191553 TI - Calcyclin-like protein from Ehrlich ascites tumour cells-Ca2(+)-binding properties, distribution and target protein. PMID- 2191554 TI - Interactions of S100 proteins with protein kinase substrates. Biological implication. PMID- 2191555 TI - Evolution of the "EF-hand" family of calcium-binding proteins. PMID- 2191556 TI - Parvalbumin expression in normal and mutant Xenopus embryos. AB - The levels and cellular distribution of PV were analyzed at the molecular level in normal and mutant Xenopus laevis embryos. In developing tadpoles, PV protein expression was restricted to fast-twitch myotomal cells, as shown by immunofluorescence experiments with myosin isoform-specific monoclonal antibodies. Both PV expressing and non-expressing myotomal cells can be cultured in vitro without neurons, and non-expressing cells have been shown to lack hybridizable levels of PV mRNA. In a paralyzed mutant, unresponsive, the level of PV protein was normal, but its cellular distribution was not. Thus, while neural input may not be necessary for PV expression in embryonic cells, one gene sequence appears needed for proper cellular distribution of PV in tadpole tail muscles. PMID- 2191557 TI - Calretinin and other CaBPs in the nervous system. AB - At least three CaBPs are abundant in various types of nerve cells: calbindin-D28, calretinin, and parvalbumin. The sequence of chick calretinin, from cDNA clones, is 60% homologous to that of chick calbindin. The genomic calretinin gene has also been partially sequenced. Calretinin is a protein of 29-30 kilodaltons. Antisera have been raised against beta-galactosidase-calretinin fusion proteins, and used to compare the distribution of calretinin with that of calbindin by two colour immunofluorescence. Some sections have also been stained for parvalbumin. In chick brain and retina, the three proteins are largely in different neurons. Calbindin and calretinin are particularly abundant in some sensory nuclei, and co expression is more common in peripheral sensory neurons. In rat brain, and in retinae of rat, cat, and salamander, some of the expression patterns are conserved, but some are not. In the chick embryonic retina, some cells show a transient phase of calbindin immunoreactivity during development. PMID- 2191558 TI - Immunohistochemical detection of 28KDa calbindin in human tissues. PMID- 2191559 TI - Comparison between rat brain calbindin- and calretinin-immuno-reactivities. PMID- 2191561 TI - Protein engineering and structure/function relations in bovine calbindin D9k. PMID- 2191560 TI - Structure of the human cDNAs and genes coding for calbindin D28K and calretinin. PMID- 2191562 TI - Mutant analysis approaches to understanding calcium signal transduction through calmodulin and calmodulin regulated enzymes. AB - An example set of site-specific mutagenesis studies of calmodulin has been discussed in terms of strategy and how the results can provide insight into the functioning of calmodulin. A set of common examples for the study of calcium binding and enzyme activation were discussed. Essentially, site-specific mutagenesis in these initial studies is a perturbation approach. From these perturbation studies, structural features can be correlated in future studies with function and mechanisms of action proposed. More importantly, the approach allows efficient testing of proposed mechanisms and further probing of the molecular aspects of the signal transduction pathways. Clearly, the key functional feature that must be addressed in future studies is how the calcium binding steps in the mechanism are coupled to the enzyme activation step, which is the final step of the calmodulin-enzyme binding mechanism. PMID- 2191563 TI - Parvalbumin, molecular and functional aspects. PMID- 2191564 TI - Unique calcium binding proteins in invertebrates. PMID- 2191565 TI - Calcium and cell steady states. PMID- 2191566 TI - Role of calcium in secretion and synthesis in bovine adrenal chromaffin cells. PMID- 2191567 TI - Ca2(+)-binding proteins as components of the cytoskeleton. PMID- 2191568 TI - [A trial of digitization and digital analysis of analog clinical images of bladder cancer]. AB - Owing to the recent developments in computed radiography and the picture archiving and communication system, all clinical images of bladder cancer can now be digitized, and recording, archiving, transportation and analysis of these images is becoming popular. We analyzed various kinds of analog images of bladder cancer after they were digitized via a simple image analyzer. The image analyzers we utilized were very useful for us to understand and become familiar with digitization of analog images of bladder cancer as well as digital analysis. PMID- 2191569 TI - [Clinical studies on endocrine therapy of prostatic carcinoma (1): Multivariate analyses of prognostic factors in patients with prostatic carcinoma given endocrine therapy]. AB - The general trend on the treatment for prostatic carcinoma has been changing from endocrine therapy alone to an alternative type according to stage. We evaluated clinically the favorable and unfavorable outcome of endocrine therapy in Japan, so that others will be appropriately evaluated. In a cooperative study made by members of five universities, 572 patients with clinically or histologically reconfirmed prostatic carcinoma were entered in this retrospective study. We studied the true influence of prognostic factors on the prognosis of 497 patients with prostatic carcinoma who had received endocrine therapy, employing multivariate analyses, such as quantification method II, multiple regression analysis and Cox's proportional hazard model. Twelve factors were considered in the study; "age", "stage", "histological findings (structural atypism = SAT, nuclear anaplasia = NAN, Gleason's primary and secondary pattern)", "pretreatment level of total acid (ACP) and of alkaline phosphatase (ALP)", "castration performed or not performed", "doses of estrogen", "type of response of local prostatic tumor and of ACP to endocrine therapy". Analysis of the "importance" of a prognostic factor by a partial correlation determined by quantification method II, revealed "stage" to have the greatest "importance" on prognosis throughout the entire period. "Response of local prostatic tumor", "response of ACP" and "Gleason's primary pattern" tended to be important factors for prognosis, in particular, in the first half period, and "age" and "Gleason's secondary pattern" were important in the latter half. Multiple regression analysis revealed the "stage", once again to be the most influential factor on the prognosis for the entire observation period. Also "response of local prostatic tumor", "SAT" and "Gleason's primary pattern" affected the patients' prognosis in the first half of the observation period. In the latter half, "age" became more of an influential factor than "histological findings". Analysis with Cox's proportional hazard model revealed that "response of ACP", "stage", "age", "Gleason's primary and secondary pattern", and "response of local prostatic tumor" were definitely the more influential prognostic factors, of which chi-square values (or t values) were statistically significant. Comparison of the significant factors in each multivariate analysis revealed that common influential prognostic factors, such as "age", "stage", "histological findings (mainly Gleason's primary and secondary pattern)", "response of local prostatic tumor" and "response of ACP" were coincident to the clinical impression. The clarification of these factors would be clinically beneficial when treating patients with endocrine therapy. PMID- 2191570 TI - [Clinical studies on endocrine therapy of prostatic carcinoma (2): Prognosis of patients with prostatic carcinoma given endocrine therapy, and analyses of causes of death and side effects of endocrine therapy]. AB - Of 572 patients with prostatic carcinoma, 497 received endocrine therapy as the initial treatment. These patients were surveyed in a cooperative research study by members from five universities. Prognosis, causes of death and side effects of estrogen therapy were studied. The prognosis of patients who had received endocrine therapy became worse, as the stage progressed. The prognosis of those who had received a combination of estrogen therapy with castration tended to be better than that of those who had received estrogen therapy alone. Similarly, the prognosis of those who had received a combination of progesterone therapy with castration tended to be better than that of those who had had progesterone therapy alone. No relationship was found between estrogen doses (low, medium and high) and prognosis, although a precise comparison among the three could not be made because of the smaller number of patents with low doses. A high dose of estrogen may not always be the indication, rather a medium dose such as 300 mg diethylstilbestrol diphosphate may be clinically appropriate. The cause of death could be identified in 303 patients who had received endocrine therapy. Cancer related death was the most frequent (63.7%), and cardio- or cerebrovascular death accounted for only 14.2% of the cases. When this analysis was confined to the patients who had received estrogen therapy, estrogen administration seemed to be the cause of cardio- or cerebrovascular death of 16.1% of the patients. Daily dosing of estrogen was not definitely related to the incidence, or the interval to cardio- or cerebrovascular death. However, among the patients who had died of cardio- or cerebrovascular disease, 50% of the patients who had received a medium or high dose of estrogen tended to die within two years after treatment, while 50% of those who had received a low dose died within three years. PMID- 2191571 TI - [Clinical studies on endocrine therapy of prostatic carcinoma (3): Histopathological features of prostatic carcinoma and its prognosis]. AB - We investigated how histopathological features, such as structural atypism (SAT), nuclear anaplasia (NAN) and Gleason's pattern, influence the prognosis of patients receiving endocrine therapy. Patients with SAT 3 or NAN 3 clearly had a lower survival rate and a shorter survival period than those with other grades of SAT or NAN and this tendency was more prominent in the high stage than low stage. Patients with a higher grade of SAT or NAN had a poorer prognosis as well, when only cancer-related death was considered in the calculation of survival and survival period. The results described above suggest that the grade of SAT and NAN is one of most influential factors for prognosis. In the analysis for the prognosis of patients according to grade of mean value of SAT + NAN, there were differences in prognosis among mean value of SAT + NAN 2-4, 5 and 6. This indicated that the combined grading system would provide more information to the prediction of prognosis. Patients with Gleason's primary (or secondary) pattern 1 and 2, or 3 and 4 had a better survival than those with pattern 5 in the analysis when only cancer-related death was considered. This was coincident with the result that the survival rate for each Gleason's sum 2-3, 4-5, 6, 7-8 and 9-10 was different. Consequently, Gleason's pattern influenced the rate of cancer related deaths, and this pattern may be another important factor for predicting the prognosis. PMID- 2191572 TI - [A case of metastatic ureteral tumor]. AB - We report a case of metastatic ureteral tumor resulting from gastric cancer in a 56-year-old female. She had undergone distal gastrectomy for gastric cancer in our hospital 3 years earlier, on the histological diagnosis of poorly differentiated adenocarcinoma with absolute curative resection. In March, 1987, she visited our hospital complaining of microscopic hematuria and lumbago. Intravenous pyelography and left retrograde pyelography revealed the stenotic change of the left ureter and hydronephrosis. Endoscopic ureteral biopsy was performed, and the histological diagnosis was an inflammatory change of the ureter. But the hydronephrosis increased, so partial ureterectomy was performed. The histological examination confirmed adenocarcinoma in the left ureter resulting from gastric cancer. From the 340th postoperative day, she complained of general fatigue and vomiting, and gastroscopy revealed recurrent gastric cancer. PMID- 2191573 TI - [A case of cystitis glandularis suspected of malignant tumor of urinary bladder]. AB - A case of cystitis glandularis is reported. A 70-year-old male was admitted to our hospital with the complaint of urinary frequency and gross hematuria. A bladder tumor was suspected by ultrasonography. Cystoscopy revealed multiple cystic lesions arising from the bladder neck and trigone. Transurethral biopsy of the bladder wall lesion revealed cystitis glandularis. Transurethral resection was performed. His postoperative course was uneventful. PMID- 2191574 TI - [A case of prostatic hemangiopericytoma]. AB - One case of prostatic hemangiopericytoma is reported. The patient was a 38-year old man who visited us complaining of difficulty in urination for 6 months duration. Before he came to us, he had undergone open prostatectomy under the suspicion of prostatic abscess++ at a previous hospital with failure because of very severe adhesion. He was referred to us under the histologic suspicion of prostatic sarcoma. From the histopathological study, he was finally diagnosed as having hemangiopericytoma. However, it was difficult to diagnose whether the lesion was benign or malignant in nature. After the external X-ray irradiation, he has been placed under our observation for these 20 years with roentgenographic followup. No infiltration or metastasis has been detected. Judging from these findings and our review of the literature, we concluded that the prostatic hemangiopericytoma reported here is benign in nature. To our knowledge, only 6 cases (5 cases from Europe and the US, and 1 case from Japan) have been reported heretofore. PMID- 2191575 TI - [Paratesticular rhabdomyosarcoma: a case report]. AB - A thirteen-year-old boy noted a swelling in his right scrotum one year prior to admission. On August 7, right high orchiectomy was performed. The tumor mass measured 10 x 6 x 7 cm. Microscopic examination revealed alveolar type rhabdomyosarcoma. Lymphangiography and computed tomography revealed retroperitoneal lymph node metastasis. He was treated with VAC therapy (vincristine, actinomycin D, cyclophosphamide) and VAD therapy (vincristine, adriamycin). This drug combination was effective, and he has been followed for two years with no evidence of recurrence. PMID- 2191576 TI - [A phase III multi-center clinical trial on 123I-orthoiodohippurate (123I-OIH)]. AB - A multi-center clinical trial was performed to evaluate the clinical usefulness of 123I-orthoiodohippurate (123I-OIH) in patients with renal and urinary disorders. 123I-OIH was evaluated to be "safe" in all 259 cases it was injected. 123I-OIH was useful in all 248 cases analyzed for the overall clinical usefulness evaluated by the investigators. The clinical significance of the drug was also evaluated in terms of renal blood flow function, renal parenchymal function, urinary function and the ability to differentiate between renal and urinary disorders. In the comparison with 123I-OIH (90 cases), 123I-OIH was superior as evaluated by the investigators and the Committee both. In the comparison with 99mTc-DTPA (113 cases), 123I-OIH was evaluated as superior by the investigators, but no significant difference was found by the Committee. In image qualities, 123I-OIH was evaluated as superior to 131I-OIH and equal to 99mTc-DTPA by the Committee. In overall efficiency, 123I-OIH was evaluated as being more valuable than 131I-OIH in 92% of the 90 cases and more valuable than 99mTc-DTPA in 50% of the 113 cases. 123I-OIH was evaluated as being less valuable than 131I-OIH in no cases and less valuable than 99mTc-DTPA in 7% of the 113 cases. These results suggest that 123I-OIH is superior to 131I-OIH and equal or superior to 99mTc-DTPA as a radiopharmaceutical for gamma camera-renography. PMID- 2191577 TI - Effect of baseline ST segment elevation on test performance of standard and heart rate-adjusted ST segment depression criteria. AB - Whether the ST segment shift used to evaluate the presence and severity of myocardial ischemia should include the additional deviation due to decreasing amounts of baseline ST segment elevation was examined in 100 clinically normal subjects and in 124 patients with coronary disease. Exercise ST segment depression was calculated in two ways: as the difference between exercise and resting ST segment depression, but excluding any resting ST elevation (STdep), and as the total ST segment difference or excursion, including any baseline resting ST elevation (STdiff). These values were also used for separate calculation of the maximal ST/heart rate slope and delta ST/heart rate index in each case. Given partition values with matched specificity of 95% in clinically normal subjects, 150 microV of STdep was significantly more sensitive for coronary disease than 220 microV of STdiff (61% [76 of 124] versus 50% [62 of 124], p less than 0.005). Comparison of receiver operating characteristic curves confirmed the superior test performance of STdep for the identification of coronary disease in this population (area under the curve 0.920 versus 0.869, p = 0.0019). In contrast, detection of three-vessel coronary obstruction by standard ST segment criteria was not affected by definition of ST segment excursion. Substitution of STdiff for STdep did not change the performance of the ST/heart rate slope of the delta ST/heart rate index for either the detection of coronary disease or for the identification of three-vessel coronary obstruction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2191578 TI - ECG variants and cardiac arrhythmias in athletes: clinical relevance and prognostic importance. AB - These findings permit the following conclusions on cardiac changes induced by high-performance sports and high levels of training. Sinus bradycardia and AV block can frequently be observed in athletes, but they do not require attention as long as they are asymptomatic or do not produce pauses exceeding 4 seconds. Persistent rather than transient second-degree AV block or Mobitz second- or third-degree AV block is an extremely unusual finding even in athletes and should be considered a sign of organic lesions until proved otherwise. Supraventricular and AV node ectopic beats are not more frequent in athletes than in the general population except for atrial fibrillation. WPW syndrome is of particular importance, since rapid conduction to the ventricle via the accessory AV pathway is possible, especially if there is a tendency toward atrial fibrillation. Likewise caution is required in athletes with hypertrophic cardiomyopathy. Here hemodynamic deterioration must be anticipated with the occurrence of supraventricular tachycardia. Simple ventricular arrhythmias occur among athletes with the same frequency as in the general population, but they usually disappear with exercise. The occurrence of complex ventricular forms of arrhythmia should always prompt cardiologic examination in search of underlying cardiac disease, particularly hypertrophic or dilated cardiomyopathy. The presence of ventricular arrhythmias without evidence of underlying heart disease does not indicate a special or increased risk of sudden cardiac death. A higher incidence of right and/or left ventricular hypertrophy, exercise-reversible ST elevation, and exercise-reversible changes in T waves (T negativity, sharp and/or excessive T waves) can be considered physiologic changes in the ECGs of athletes. These changes correlate closely with the type of sports activity and degree of training and are reversible when the activity is stopped. Horizontal ST segment depression are by contrast very rare in athletes and should always be clarified by cardiologic examination. Exercise-induced sudden cardiac death in athletes is unusual without preexisting heart disease. The cause of sudden cardiac death among athletes less than 40 years of age can be predominantely ascribed to congenital heart diseases (such as hypertrophic cardiomyopathy or coronary anomalies). In athletes more than 40 years of age and with increasing age, coronary heart disease is the most frequent autopsy finding. A corresponding risk stratification should take these partial dangers into account. PMID- 2191579 TI - Assessment of normal and atherosclerotic arterial wall thickness with an intravascular ultrasound imaging catheter. AB - A prototype intravascular ultrasound imaging catheter with a 20 MHz transducer was used to obtain 59 cross-sectional images in 14 segments of human atherosclerotic arteries. Three distinct components of the arterial wall were visualized on the ultrasound images: a highly reflective intima, an echolucent media, and a moderately reflective adventitia. Images were obtained at 1 mm increments in vitro and were compared with histologic sections at the same levels. Measurements of the arterial layers showed a close correlation between ultrasound images and histologic sections for the thickness of the intimal plaque (r = 0.91), the media (r = 0.83), and the total wall thickness (r = 0.85). The ultrasound images overestimated the mean intimal and total wall thickness by 0.3 mm and 0.7 mm compared to measurements in histologic sections (p less than 0.001). Intravascular imaging with high-frequency ultrasound is an accurate method for measuring microanatomic arterial dimensions and the extent of atheromatous involvement of the arterial wall. This method could represent an important adjunct to traditional angiographic techniques for assessing the severity of atherosclerosis. PMID- 2191580 TI - Pericardial drainage. PMID- 2191581 TI - Reocclusion three months after successful thrombolytic treatment of acute myocardial infarction with anisoylated plasminogen streptokinase activating complex. AB - Thirty consecutive patients with acute myocardial infarction (AMI) were treated with anisoylated plasminogen streptokinase activating complex (APSAC) within 4 hours after onset of symptoms. After 1.5 and 48 hours, patency of the infarct related vessel and the quantitative degree of residual diameter stenosis were studied by selective coronary angiography. Ventriculograms were made to determine the global left ventricular ejection fraction. Patients showing patency at 48 hours were reevaluated angiographically after 3 months. At 1.5 and 48 hours after APSAC administration patent vessels were demonstrated in 65 and 69% of patients, respectively. Mean residual stenosis decreased significantly from 56 +/- 11% at 1.5 hours to 46 +/- 13% at 48 hours (p less than 0.01). Patients not responding to thrombolytic therapy showed significant deterioration of the left ventricular function during the first 48 hours after AMI. Side effects were minor and mainly associated with invasive procedures. Despite adequate oral anticoagulation, angiographically documented reocclusion at 3 months amounted to 28%. Reocclusion, however, was neither associated with clinically documented reinfarction, nor with a decrease in the left ventricular ejection fraction. Our study shows that APSAC is an effective thrombolytic agent in AMI but that late reocclusion may occur. Oral anticoagulants appear to be less effective in the prevention of reocclusion in the treatment regimen after thrombolysis. PMID- 2191582 TI - Long-acting, marked antiischemic effect maintained unattenuated during long-term interval treatment with once-daily isosorbide-5-mononitrate in sustained-release form. AB - In 18 patients with documented coronary artery disease, the antiischemic effect of 50 and 100 mg isosorbide-5-mononitrate (IS-5-MN) in sustained-release (SR) form was investigated using a randomized, double-blind, crossover, placebo controlled protocol. After the initial administration of both dosages, compared to placebo there were significant reductions in exercise-induced ST-segment depression and significant increases in ischemia-free exercise time at all times of testing. At 12 hours, the 100-mg dosage still amounted to greater than 50% of its maximum and was significantly more marked than the 50 mg dose. Accordingly, the 100-mg dosage can be assumed to confer a longer duration of action. At the end of 3 weeks of long-term treatment, the significant antiischemic effects were not diminished versus those observed after initial administration. There was no evidence of tolerance development with either dosage. The IS-5-MN plasma concentration during long-term administration displayed, within the 24-hour treatment cycle, a clear decrease to low baseline values and a marked 5- to 7 fold increase after the daily dose in accordance with the response known to be prerequisite to successful interval treatment. Thus, the once-daily administration of IS-5-MN SR with dosages of 50 mg and, more markedly, 100 mg, provides effective antiischemic protection throughout the daily period of most physical activities in patients with stable angina pectoris. PMID- 2191583 TI - Superior vena cava Doppler flow velocity patterns in pericardial disease. AB - Doppler superior vena cava (SVC) flow patterns were studied in 34 patients with pericardial disease and in 8 normal adults; the pulse transducer on the echocardiographic instrument was used for respiratory monitoring, rather than a separate nasal thermistor-based device. First expiratory SVC diastolic flow velocities (Dfe) did not differ in normal subjects and patients with hemodynamically insignificant pericardial effusions (23 +/- 3 cm/s and 29 +/- 13 cm/s, difference not significant). Dfe were less than 15 cm/s only in the 14 patients with cardiac tamponade (9 +/- 3 cm/s, p less than 0.01). A ratio of systolic to diastolic flow velocity less than or equal to 1.1 in the first expiratory beat distinguished constrictive pericarditis from all other groups (p less than 0.01), although not from restrictive cardiomyopathy. Expiratory ablation of diastolic SVC flow mimicking cardiac tamponade was not observed in constrictive pericarditis. Respiratory variation in SVC flow velocities was slight in normal subjects and patients with constrictive pericarditis, increased in patients with hemodynamically insignificant pericardial effusions (p less than 0.01) and greatest in patients with cardiac tamponade (p less than 0.01). Quantitative analysis of SVC flow velocity patterns is a useful addition to the echocardiographic evaluation of pericardial disease. PMID- 2191584 TI - Peripheral action of spironolactone: plethysmographic studies. AB - The relation between vasodilation and the blood pressure-reducing action of spironolactone was studied in a randomized, placebo-controlled, double-blind, crossover study using 9 patients with essential hypertension. Vasodilation was studied by measuring blood flow in finger and calf (representative of skin and muscle circulation) by an electrocardiographic-triggered venous-occlusion plethysmograph. Treatment with spironolactone (100 mg twice daily for 4 weeks) produced significant decreases in systolic and diastolic blood pressure without significantly affecting heart rate. Blood flow through finger and calf increased, sometimes markedly, in 6 of the 9 patients, while vascular resistance decreased. This study confirms that the antihypertensive action of spironolactone is associated with vasodilation in many patients. PMID- 2191585 TI - Clinical update: spironolactone and altizide as monotherapy in systemic hypertension. AB - A large-scale, open, nonrandomized, multicenter, 90-day study of the safety and efficacy of a thiazide diuretic and aldosterone antagonist combination (Aldactazine, 25 mg spironolactone and 15 mg altizide, 1/day) as monotherapy was performed in 946 patients with mild to moderate hypertension (diastolic blood pressure [BP] between 90 and 120 mm Hg). Adverse effects were assessed, and body weight, heart rate, serum potassium, creatinine and uric acid measurements were monitored. On day 45 of the study, BP was normalized (diastolic BP less than or equal to 90 mm Hg) in 72% of the patients. The dose was increased to 2 tablets per day in the patients whose BP did not reach normal levels. By the end of the study, BP was controlled in 83% of the patients. No significant changes were noted in body weight, heart rate or laboratory values; however, treatment had to be discontinued in 6 patients because of hypokalemia (n = 4) or elevated serum creatinine levels (n = 2). Serum uric acid levels were increased in 5.5% of patients. The rate of adverse effects, as reported by the patients, was low (5%). Thus, this study demonstrates that diuretics, especially the combination of a thiazide diuretic and aldosterone antagonist, remain a safe, effective and economical therapy for patients with mild to moderate hypertension. PMID- 2191586 TI - Spironolactone and altizide versus converting enzyme inhibitor (enalapril). AB - The safety and antihypertensive effectiveness of a fixed-dose combination form of spironolactone + altizide (S/A) were compared with those of enalapril, an angiotensin-converting enzyme inhibitor in a randomized, double-blind, parallel group study of 186 patients with moderate essential hypertension. The 2 treatment groups were comparable in terms of age, gender, duration and severity of hypertension, diastolic blood pressure (BP), serum potassium and creatinine, and 24-hour urinary sodium excretion after a 4-week washout phase. After 8 weeks of treatment, both S/A and enalapril decreased BP significantly and to about the same extent. Enalapril, however, was more effective in decreasing supine diastolic BP in patients younger than age 50, whereas S/A yielded better results in those older than 50. Laboratory values were similar after both drugs were administered, and there were no clinically significant changes. The study demonstrated that S/A safely reduces elevated BP, particularly in older patients. PMID- 2191587 TI - Spironolactone and altizide used in combination with enalapril: twenty-four-hour ambulatory recording of blood pressure. AB - The addition of enalapril or acebutolol to a regimen of altizide + spironolactone in patients with moderate hypotension was investigated in a multicenter study of 53 patients. The patients underwent semiambulatory 24-hour blood pressure monitoring, especially to observe hypotensive episodes. In the 25 patients uncontrolled with altizide + spironolactone alone, enalapril and acebutolol were about equally effective in reducing blood pressure. The incidence of hypotension was low and comparable for both treatment groups, provided that the initial dose of angiotensin-converting enzyme inhibitor was low (5 mg). PMID- 2191588 TI - Spironolactone versus nifedipine in essential hypertension. AB - In a double-blind, randomized, multicenter study of 194 patients with moderate hypertension, spironolactone and nifedipine were found to reduce blood pressure (BP) to about the same extent and in the same percentage of patients after 45 days of treatment (47 and 50%, respectively). At that point, the patients controlled by either drug continued on their regimen for another 45 days, while patients whose BP was still elevated (diastolic BP greater than 90 mm Hg), received the other drug in addition. After 45 days of combination therapy, 63% of the patients had normal BP, whereas those receiving monotherapy largely remained normotensive (96% in the spironolactone group and 88% in the nifedipine group). The adverse effects were not severe with either group, but the incidence was markedly higher in the nifedipine group. PMID- 2191590 TI - Milo Hellman--a man of science. PMID- 2191589 TI - Aldactazine/captopril combination, safe and effective in mild to moderate systemic hypertension: report on a multicenter study of 967 patients. AB - The safety and efficacy of a thiazide/potassium-sparing diuretic and an angiotensin-converting enzyme inhibitor used concomitantly was evaluated in a large, multicenter study. Aldactazine was administered alone for 2 months, after which time captopril was added in those whose blood pressure had not normalized (332 patients). At the end of the 6-month study, control of blood pressure was achieved in 88% of the patients with one or the other regimen. No clinically significant changes were recorded for a number of biologic parameters. Specifically, there was 1 case of hyperkalemia (6 mmol/liter), a very low incidence of hypotension (1.6%), and a low rate of adverse effects. Therefore, such a combination could provide important therapeutic benefits in hypertensive patients. PMID- 2191591 TI - Orthodontics and temporomandibular disorders: a review of the literature (1966 1988) AB - The orthodontist has been both accused of causing and complimented for curing temporomandibular dysfunction. To better understand the origins of these conflicting opinions, a review of the orthodontic and temporomandibular joint journals was performed for articles published since 1966. A total of 91 publications that discussed the relationship between orthodontics and temporomandibular disorders was found, and these articles were divided in three categories: viewpoint publications, case reports, and sample studies. Among the areas scrutinized in each category was the method that has led to the diversity of viewpoints. From this analysis, the following conclusions were drawn: (1) viewpoint publications and case reports were excessively represented in comparison with the number of sample studies; (2) viewpoint publications and case reports described a wide variety of conflicting opinions on the relationship between orthodontics and temporomandibular disorders; (3) unlike sample studies, viewpoint publications and case reports have little or no value in assessment of the relationship between orthodontics and temporomandibular disorders; (4) sample studies indicate that orthodontic treatment is not responsible for creating temporomandibular disorders, regardless of the orthodontic technique; and (5) sample studies indicate that orthodontic treatment is not specific or necessary to cure signs and symptoms of temporomandibular dysfunction. PMID- 2191592 TI - Sclerosants for variceal sclerotherapy: a critical appraisal. AB - Endoscopic sclerotherapy is a well-accepted technique for the treatment of variceal bleeding. It is carried out by injecting a sclerosant into or around a varix. Sclerosants are oily or aqueous chemicals which produce sclerosis, depending on their necroinflammatory and thrombotic properties. The safety and efficacy of various sclerosants has been evaluated in experimental and human studies. However, due to the presence of a large number of variables, conflicting results have been reported. Based primarily on anecdotal experiences, sodium tetradecyl sulfate, ethanolamine oleate, polidocanol, and alcohol appear to be potent and safe sclerosants. There is great need to perform double-blind trials to identify ideal sclerosant(s) with optimum thrombogenic and minimum necroinflammatory properties. PMID- 2191593 TI - Changes of intrahepatic localization of hepatitis B core antigen in HBeAg positive patients with chronic active hepatitis B treated with interferon. AB - The intrahepatic distribution of hepatitis B core antigen (HBcAg) was studied in 14 HBeAg-positive patients with chronic active hepatitis B who were treated with interferon. Patients received 5 to 6 million units daily of human lymphoblastoid interferon or human diploid fibroblast interferon for 28 days. Intrahepatic HBcAg was detected by the indirect immunoperoxidase technique. Before interferon therapy, the intrahepatic HBcAg was detected almost equally in both the nucleus and cytoplasm. The expression of nuclear HBcAg decreased significantly (p less than 0.001) after interferon therapy, irrespective of the outcome for DNA polymerase and/or HBeAg/anti-HBe status. The expression of cytoplasmic HBcAg decreased significantly (p less than 0.05) only in the patients who lost DNA polymerase after treatment, whereas it increased in patients with DNA polymerase and/or HBeAg in the serum. These findings suggested that a shift of intrahepatic HBcAg from the nucleus to the cytoplasm occurred in HBeAg-positive patients with chronic active hepatitis B receiving interferon therapy. PMID- 2191594 TI - Clinical application of endoscopic ultrasonography. AB - During the course of routine clinical practice in 48 patients, 50 endoscopic ultrasound (EUS) examinations were performed over a 1-yr period, with all patient data collected prospectively. Organs examined were the esophagus, stomach, duodenum, ampulla, pancreas, common bile duct, and gallbladder. There were 18 staging exams of known neoplasms, and 24 examinations to evaluate possible mass. Forty-three examinations were successful, four failed due to instrument malfunction, and three were technical failures. Among 35 exams for masses, follow up pathology was available in 21 and confirmed EUS findings in 90%. EUS yielded additional information, not available by other imaging studies, in 60% of successful exams. No complications were seen. The recent literature is reviewed in approximately 2000 patients. We conclude that EUS is an accurate and safe method for evaluating upper gastrointestinal pathology, particularly for staging neoplasms. PMID- 2191595 TI - Esophageal acid contact time and heartburn in acute treatment with ranitidine and metoclopramide. AB - Ranitidine and metoclopramide were compared for their ability to reduce esophageal acid contact time and heartburn. Twelve patients with histories of heartburn received ranitidine 150 mg bid, metoclopramide 10 mg qid, and placebo (ranitidine-matched) bid in a randomized, open-label, crossover fashion. Esophageal pH was monitored with an antimony electrode and portable recording unit for 24 h under strictly controlled laboratory conditions. Ranitidine significantly (p less than or equal to 0.05) reduced 24-h acid contact time from 11.6% to 6.4%. Reflux episode frequency was also significantly (p less than or equal to 0.05) reduced from 82 to 45 episodes per day and from 12 to 2 episodes at night. In contrast, metoclopramide did not reduce 24-h acid contact time or daytime reflux episode frequency, although nighttime episode frequency was significantly (p less than or equal to 0.05) decreased. Only ranitidine significantly reduced heartburn frequency and severity. We conclude that acute treatment with ranitidine, but not metoclopramide, significantly reduces esophageal acid contact time, reflux episode frequency, and heartburn frequency and severity in patients with gastroesophageal reflux. PMID- 2191596 TI - Mastery in clinical occupational therapy. AB - This study sought to describe the characteristics of mastery in occupational therapy practice. A Delphi survey (i.e., an inquiry technique used to predict and define constructs [Linstone & Turoff, 1975]) of 33 occupational therapy experts was conducted to obtain their conceptions of the characteristics of occupational therapy mastery. Three master clinicians, identified by the expert respondents, were then interviewed to validate and illustrate the concepts of mastery identified in the Delphi survey. The results suggest that mastery is a combination of selected personal traits, creative and flexible judgment, the use of occupation as the foundation for practice decisions, and a strong commitment to occupational therapy practice. Further, mastery is expressed through a personal style that is unique to each clinical master. PMID- 2191597 TI - The effect of rhizotomy on movement in patients with cerebral palsy. AB - Selective posterior lumbar rhizotomy has recently become an alternative method for relieving spasticity in patients with spastic cerebral palsy. This procedure involves the selective sectioning of the lumbosacral posterior nerve rootlets. Because the whole nerve root is not cut, tactile and proprioceptive sensation remain intact. The present study measured the changes that occurred in 29 patients with spastic cerebral palsy 2 days before surgery and from 4 to 14 months after surgery. Each patient was used as his or her own control. In addition to the clinical evaluation of function, gait was analyzed on appropriate patients with a simple digital camera and microcomputer. The results indicated positive gains after rhizotomy. These gains were, however, dependent on the patients' abilities before surgery. The most significant improvement occurred in thigh and knee ranges of movement. This somewhat controversial new method of treating spasticity shows promise in improving the quality of life of patients with spastic cerebral palsy and in facilitating their treatment. PMID- 2191598 TI - The integration of computers into the occupational therapy department. AB - Despite the growing interest in and use of microcomputers as an occupational therapy assessment and treatment modality, many factors still limit their widespread adoption in the clinical milieu. Such factors include inadequate background preparation; insufficient financial resources; the overwhelming number of choices of computer hardware, software, and adaptive devices; lack of product support; rapidity of change; and skepticism of administrators and clinicians. The purpose of this paper is to outline procedures that will facilitate the integration of microcomputers into the clinical milieu by (a) identifying the reasons why and how these devices are used improperly; (b) proposing ways to correct these problems; (c) providing recommendations concerning the acquisition of major microcomputer hardware, software, and adaptations; and (d) providing an annotated list of resources for further information. PMID- 2191599 TI - A computer program for enhancing visuomotor skills. PMID- 2191600 TI - [Clinico-laboratory criteria of cerebrovascular disorders in newborn infants]. PMID- 2191601 TI - [The role of ultrasonic examination using a vaginal sector probe in the evaluation of the endometrium and follicles during spontaneous and stimulated ovulation]. PMID- 2191603 TI - [Prenatal ultrasonic diagnosis of developmental defects of the kidneys and urinary tract]. PMID- 2191602 TI - [Intranatal computerized cardiotocography]. PMID- 2191604 TI - History of medicine in Alaska. William Harvey Ivy, M.D. PMID- 2191605 TI - Hairy polyp of the oropharynx. A case report with speculation on nosology. AB - The hairy polyp of the oronasopharynx is a rare congenital malformation that has been classified as a dermoid, teratoid, teratoma, or hamartoma in the past. A case of oropharyngeal hairy polyp is presented that occurred in a male neonate with severe intermittent respiratory obstruction. The precise nosology of this unusual malformation is discussed, with the speculation that it is classified as a choristoma. PMID- 2191606 TI - Giulio Turcato's abstract depiction of the skin. PMID- 2191607 TI - Schools of thought. Medical typologies in literature. PMID- 2191608 TI - [Low density lipoprotein (LDL) heterogeneity and atherosclerosis]. AB - LDL particles constitute the predominant form of transport of cholesterol towards tissues, and a major risk factor for atheroma. The pathogenesis of atherosclerosis is, as yet, far from completely elucidated and, indeed, within the LDL particles themselves, there is a structural heterogeneity. Approximately fifteen subfractions have been isolated so far, presenting differing profiles in normal and hyperlipidemic subjects. Some of these subgroups seem to be linked with an atherogenic potential, this is the case for the smaller and the more dense of the particles. LDL particles are normally cleared from the blood stream via the BE receptor, whose synthesis is regulated by the intracellular content of cholesterol. The particules must however undergo several, in vivo and in vitro, transformations which modify their metabolism and are all the more important when their half life is prolonged. These transformations, and in particular oxydation, lead, via the macrophage pathway, to the accumulation of cholesterol, the creation of foam cells, and ultimately to the formation of the lipid streak. Antioxydants therefore open the way to new therapeutic pathways by acting in synergy with cholesterol lowering agents. PMID- 2191609 TI - [Determination of fibrinopeptide A (FpA): comparison of an enzymatic method and isotopic method with reference to ventilation-perfusion scintigraphy]. AB - Fibrinopeptide A becomes free after thrombolysis of fibrinogen in thrombo-embolic situation. In view to quantify this molecule, the authors have compared two different methodologies (enzymatic and isotopic). Isotopic scintigraphy of lung (ventilation-perfusion) served as reference in this study for pulmonary thrombosis. PMID- 2191610 TI - [Contribution of immunoenzymatic technics to the assay of anti-native DNA antibodies in the biological diagnosis of lupus erythematosus disseminatus]. AB - Anti native DNA antibodies (anti nDNA Ab), which are a highly specific feature of systemic lupus erythematosus (SLE) were measured by 3 methods: an enzyme linked immunosorbent assay (ELISA), an indirect immunofluorescence test on Crithidia luciliae (IFCL) and the Farr assay (reference test). 114 sera from patients with SLE or another connective tissue disease or without autoimmune rheumatic disease were tested. This study showed that ELISA seemed to be a more sensitive and specific test than IFCL (classical test). ELISA was also as sensitive as the Farr assay. ELISA should replace IFCL for the diagnosis and the follow up of patients with SLE. In other connective tissue diseases, ELISA might give more positive results. Thus these had to be confirmed, especially in the case of low antibodies levels, by using another method (e.g., the Farr assay). PMID- 2191611 TI - [Multiple myeloma in 1990]. PMID- 2191612 TI - [Treatment of autoimmune neonatal thrombocytopenia with high-dose intravenous immunoglobulins]. AB - During the neonatal period, 6 infants born to mothers with auto-immune thrombocytopenia purpura were diagnosed as having severe thrombopenia (platelet counts below 30 X 10(9)/l). High doses of intravenous immunoglobulins (IVIG) (0.4 g/kg/injection for 2 infants and 1 g/kg/injection for 4 infants) were administered as of the first week of life. Short-term efficacy was good in all cases (platelet counts over 50 X 10(9)/l, 2-10 days after the first injection). During the second week of life, 5 newborns had relapses which were rapidly reversed by one or several IVIG injections. The thrombopenia was cured between days 19 (shortest) and 41 (longest) and, more over, no side effects were observed. High doses of IVIG seem to be an effective and well-tolerated treatment for neonatal auto-immune thrombopenia, and they can be recommended over classical treatments (corticotherapy, exchange transfusion, platelet transfusion) as a first line of attack. PMID- 2191613 TI - [Carotid artery occlusion disclosed by cerebral ischemia. Lesional, etiologic and developing aspects]. AB - The authors report on a series of 100 patients, who underwent an ischemic cerebrovascular accident (CVA) (8 transient attacks, 15 minor CVAs and 77 completed strokes) which revealed internal carotid artery occlusion (unilateral in 93 cases and bilateral in 7), proven by ultrasonography and/or angiography. The computerized tomography scan was normal in 8 cases. The middle cerebral artery territory was involved in 84 patients (isolated or associated (25 patients) with another site), whereas an isolated watershed infarction was the only lesion in the other 8 patients. Twenty-two patients died during the acute phase. Among the 68 survivors followed for a long time, 28 were severely incapacitated. The occlusions were not atherosclerotic in 18 cases (8 spontaneous dissections, 5 cardiogenic emboli, 3 radiation-induced arteries, 2 multiple causes). Eighty-two patients had atherosclerotic thromboses (67 men and 15 women, mean age 63.1 +/- 12.7 years). Among them, 24 had previously experienced minor ischemic strokes. In this group, the two year survival rate was 63 p. 100. Patients with non-fatal atherosclerotic thromboses were followed for an average of 22.2 months, during which time 28.2 p. 100 experienced another stroke. PMID- 2191614 TI - [Acute renal insufficiency caused by drugs or iodinated contrast media. Results of a prospective and multicenter study in south Tunisia]. AB - In order to determine the frequency of acute renal failure (ARF) induced by drugs, to identify the agents responsible for it and to define its semiological characteristics, a prospective study was carried out between 1 October 1987 and 30 September 1988, in Sfax and southern Tunisia. Three Departments of Medicine and one Hemodialysis Center participated in this study. Twelve cases of drug induced ARF were identified among the 73 cases of ARF reported, i.e., a frequency of 16%. Anti-inflammatory non-steroidal drugs (AINS) were implicated in 5 cases and antibiotics in 2. Symptoms of hypersensitivity were observed in 4 patients, 2/3 without oliguria. Renal insufficiency was usually marked: plasma creatinine was 523 +/- 425 mumol/l; proteinuria greater than 1 g/24 h was seen in 2 patients. Hypovolemia and/or hypotension (6 cases) and diabetes mellitus (4 patients) were found to favor ARF. Renal function returned to normal in 9 patients, whereas mild renal failure persisted in the remaining 3 patients. Drug induced ARF occurs often. AINS are the most frequently incriminated agents and hypersensitivity symptoms without oliguria are the most common manifestations. Drug-induced ARF can be prevented by close monitoring of high-risk patients, i.e., those taking AINS. PMID- 2191615 TI - [Glucose transporters]. PMID- 2191616 TI - [Insulin receptors]. PMID- 2191617 TI - [Muscular involvement in human immunodeficiency virus infection]. PMID- 2191618 TI - [Towards the rehabilitation of maintenance electroconvulsive therapy?]. AB - ECT is a reliable treatment of serious affective disorders more efficacious than antidepressants either used alone or combined with mood stabilizers or neuroleptics. Recurrent affective disorders refractory to all treatments presently available have been tentatively treated by prophylactic ECT since the beginning of ECT. In this study, 16 cases of recurrent affective disorders treated with maintenance ECT are discussed. Six continue to show a good response to maintenance ECT. Six remain improved although they discontinued ECT. ECT failed to improve 4 patients. Indications and inclusion criteria of maintenance ECT are defined. Good responses in cases refractory to all other treatment strategies are promising but still require prospective studies, difficult to implement, in order to confirm the efficacy of maintenance ECT. PMID- 2191619 TI - [Medicopsychiatric aspects of cardiac graft]. PMID- 2191620 TI - [Psychiatry and institution. Psychiatrists and prostheses]. PMID- 2191621 TI - [Problems posed by dental implants and prostheses in daily practice at the department of psychiatry of a general hospital]. PMID- 2191622 TI - [Grafts of the kidney and liver. Medicopsychological aspects]. PMID- 2191623 TI - [Neuropsychological changes and psychiatric complications observed in a population of patients with liver transplantation]. PMID- 2191624 TI - Characterization of arsenopyrite oxidizing Thiobacillus. Tolerance to arsenite, arsenate, ferrous and ferric iron. AB - Two strains of Thiobacillus, T. ferrooxidans and T. thiooxidans, have been isolated from a bacterial inoculum cultivated during a one-year period in a 1001 continuous laboratory pilot for treatment of an arsenopyrite/pyrite concentrate. The optimum pH for the growth of both strains has been found to be between 1.7 and 2.5. Because of the high metal toxicity in bioleach pulps, the tolerance of T. ferrooxidans and T. thiooxidans with respect to iron and arsenic has been studied. The growth of both strains is inhibited with 10 g/l of ferric ion, 5 g/l of arsenite and 40 g/l of arsenate. 20 g/l of ferrous iron is toxic to T. ferrooxidans but 30 g/l is necessary to impede the growth of T. thiooxidans. PMID- 2191625 TI - Regeneration of NADH and ketone hydrogenation by hydrogen with the combination of hydrogenase and alcohol dehydrogenase. Scientific note. AB - The regeneration of nicotinamide-adenine dinucleotide (reduced form, NADH) by the reaction of NAD with hydrogen gas was carried out in the presence of the hydrogenase from Alcaligenes eutrophus. And the formations of alcohol, CO2, and 6 phospho-gluconate were observed by a combination of the above system and corresponding dehydrogenases. NADH was regenerated by hydrogen gas with the hydrogenase and recycled in these reactions. PMID- 2191626 TI - In situ bubble fractionation strategies for separating individual proteins in a batch baker's yeast fermentation process. AB - Extracellular proteins produced by yeast have been observed to stratify in the extracellular fluid of a batch bioreactor, thus creating a vertical concentration gradient. We observed that, in the four different experiments conducted, each varied in their protein recovery characteristics. For example, sparging the system with gas accentuates the separation, though even in a nonsparged system, the in situ generation of minute carbon dioxide bubbles by yeast cells creates a protein gradient as the bubbles carry proteins upward. Based on these and other observations, we propose possible strategies for recovering the individual proteins from a system containing the four major proteins considered. A simple steady-state mathematical model, based on convective upward protein transport being balanced by downward protein diffusion, has been used to describe the behavior of each of these four extracellular proteins in the fermentation broth. PMID- 2191627 TI - The antioxidants of human extracellular fluids. AB - The antioxidants in the aqueous phase of human plasma include ceruloplasmin, albumin (the protein itself and possibly also albumin-bound bilirubin), ascorbic acid, transferrin, haptoglobin, and hemopexin. Assays that attempt to answer the question "what is the most important antioxidant?" are compared, it being concluded that the answer is different depending on the nature of the prooxidant stress imposed in the assay. PMID- 2191628 TI - Purification, characterization, and complete amino acid sequence of a thioredoxin from a green alga, Chlamydomonas reinhardtii. AB - Two thioredoxins (named Ch1 and Ch2 in reference to their elution pattern on an anion-exchange column) have been purified to homogeneity from the green alga, Chlamydomonas reinhardtii. In this paper, we described the properties and the sequence of the most abundant form, Ch2. Its activity in various enzymatic assays has been compared with those of Escherichia coli and spinach thioredoxins. C. reinhardtii thioredoxin Ch2 can serve as a substrate for E. coli thioredoxin reductase with a lower efficiency when compared to the homologous system. In the presence of dithiothreitol (DTT), the protein is able to catalyze the reduction of porcine insulin. Thioredoxin Ch2 is as efficient as its spinach counterpart in the DTT or light activation of corn NADP-malate dehydrogenase, but it only activates spinach fructose-1, 6-bisphosphatase at very high concentrations. The complete primary structure of the C. reinhardtii thioredoxin Ch2 was determined by automated Edman degradation of the intact protein and of peptides derived from trypsin, chymotrypsin, clostripain, and SV8 protease digestions. It consists of a polypeptide of 106 amino acids (MW 11,808) and contains the well-conserved active site sequence Trp-Cys-Gly-Pro-Cys. The sequence of the algal thioredoxin Ch2 has been compared to that of thioredoxins from other sources and has the greatest similarity (67%) with the thioredoxin from Anabaena 7119. PMID- 2191629 TI - Production of recombinant human tropoelastin: characterization and demonstration of immunologic and chemotactic activity. AB - Tropoelastin cannot readily be prepared in quantity from natural sources and this has limited research in several important areas including structure/function relationships and fiber assembly. In order to eliminate this limitation, human tropoelastin has been expressed in a recombinant bacterial system and the protein has been highly purified. The size, amino acid composition, and sequence of the amino terminus of the recombinant tropoelastin (rTE) all agree with values predicted by the nucleotide sequence of the cDNA used in the expression vector. The rTE exhibits cross-reactivity with antibodies directed against a mixture of peptides derived from human elastin as well as antibody against a defined peptide located at the carboxy terminus of the protein. In addition, the rTE is chemotactic for fetal calf ligament fibroblasts. These results suggest that rTE could be a useful reagent for many types of studies. PMID- 2191630 TI - Histamine H1-receptor of vascular endothelial cells cultured from guinea pig skin. AB - In this study, a new procedure for the cultivation of dermal vascular endothelial cells from guinea pig ear lobe was established, and specific binding of [3H]mepyramine to the cultured cell membranes was demonstrated. The vascular endothelial cells were successfully isolated from the dermis of guinea pig ear lobes by the intravenous injection of dispase. Guinea pig serum, as a supplementary component in culture medium, is more suitable for the culture of guinea pig dermal vascular endothelial cell than is fetal calf serum. The [3H]mepyramine binding study indicated the presence of a large number of H1 receptors on the membrane of dermal vascular endothelial cells of guinea pigs, suggesting the important role of endothelial cells in cutaneous reactions to histamine. PMID- 2191632 TI - Biochemical parameters of initiation and regulation of sperm motility. AB - Studies of in vitro models demonstrate that a forward motility protein (FMP) is required for the initiation of forward motility in the immature epididymal spermatozoa. FMP is a heat-stable glycoprotein derived from epididymal plasma. During the epididymal maturation of spermatozoa in vivo, there is a marked increase of intrasperm pH and level of cyclic adenosine monophosphate (cAMP). Several studies suggest that exogenous FMP in concert with elevated intrasperm pH and level of cAMP initiates flagellar motility during the epididymal transit of sperm. cAMP activates sperm cytosolic cAMP-dependent protein kinases, which in turn phosphorylate multiple intrasperm phosphoproteins that may regulate flagellar motility. Exogenous calcium ion activates intact sperm motility, although it inhibits motility of demembranated cells on reactivation. Occurrence of cAMP-dependent type I and II protein kinases, a novel cAMP-independent protein kinase, and a phosphoprotein phosphatase has been demonstrated on the external surface of spermatozoa. The sperm surface has a coupled-enzyme system: ecto-cAMP independent protein kinase and phosphoprotein phosphatase that regulate the phosphorylation and dephosphorylation of endogenous sperm ectophosphoproteins. The specific activities of these ecto-enzymes increase markedly during forward progression, suggesting that they may have a role in regulating flagellar motility. PMID- 2191631 TI - Preventive measures for microflora and mycotoxin production in foodstuffs. AB - The conservation of foodstuffs by chemical or physical methods is now practiced on a wide scale. Certain procedures (drying, use of pesticides) are well proved and are used on an industrial scale, although in certain situations they are not without risk to human health. New techniques (controlled atmospheres, irradiation, fumigation) are in use and will undoubtedly see further development for conservation of seeds and cereals in both industrialized and non industrialized countries. In the latter case, the use of cost-effective fumigants may be of particular value. Preventive measures for the control of molds in foodstuffs are discussed in this report. PMID- 2191633 TI - Treatment selection considerations for the hypertensive diabetic patient. AB - Hypertension occurs with twice the frequency in the diabetic population as compared with the general nondiabetic population. Treatment of hypertension in diabetics can be complicated by diabetic complications and the potential for adverse effects from selected antihypertensive drugs. A rational approach to antihypertensive therapy in diabetics with or without concurrent diabetic complications incorporates a "stepped" approach to therapy that includes alternative step 1 agents (eg, angiotensin-converting enzyme inhibitors and calcium channel blockers) rather than traditional agents (eg, diuretics and beta blockers). Evolving evidence with angiotensin-converting enzyme inhibitors reveals that they do not exacerbate complications of diabetes mellitus and also may arrest or slow the progression of diabetic nephropathy. Treatment algorithms for a stepped approach to the management of the hypertensive diabetic patient are proposed. PMID- 2191634 TI - Combination of converting enzyme inhibitor with diuretic for the treatment of hypertension. AB - In recent years there has been increased discussion about goals of antihypertensive therapy other than blood pressure reduction. The development of angiotensin-converting enzyme inhibitors has provided a class of drugs with a very low side-effect profile. However, single-drug therapy is effective in only about half of hypertensive patients. In the past, diuretics have traditionally been used as the initial or second antihypertensive. Increasingly, diuretic therapy is being avoided, and other antihypertensive combinations are being used. In controlled trials, combination converting enzyme inhibitor-diuretic therapy is effective in about 85% of patients. This synergistic combination allows the diuretic dose to be reduced so that the adverse effects and metabolic complications are minimized. At this time, the combination of converting enzyme inhibitor and diuretic provides an ideal choice in terms of efficacy, compliance, side effects, and cost. PMID- 2191635 TI - Societal effects and other factors affecting health care for the elderly. Report of the Council on Scientific Affairs. AMA Council on Scientific Affairs. AB - With advances in medical care, life expectancy of Americans has increased dramatically. The increase in the size of the elderly population has had a major impact on health care provision and will have an even greater impact on our health care system over the next several decades. Although today's medical students will spend nearly half of their collective careers caring for the elderly, insufficient numbers of students show an interest in geriatrics. American society has become in many ways less traditional, and age is no longer seen as "a pathway to wisdom." Since we are now a more mobile society, extended families tend to scatter, and the elderly are frequently alone. We examine the effects of our rapidly changing, youth-oriented society on health care for the elderly. PMID- 2191636 TI - Does multiple-dose charcoal therapy enhance salicylate excretion? AB - Multiple-dose charcoal therapy has been shown to increase the excretion of some drugs. This study assesses the effects of this intervention on salicylate excretion in the postabsorptive phase. Ten human volunteers participated in this randomized, controlled, crossover, two-limbed protocol. On two occasions each volunteer ingested 2880 mg of aspirin. During the experimental limb, 25 g of activated charcoal was ingested at 4, 6, 8, and 10 hours after drug ingestion. Pharmacokinetic data were derived from serial serum salicylate concentrations, and urinary salicylate excretion was quantified. Treatment effects were 9% and 18%, respectively. Although both are significant, they are clinically modest, making multiple-dose charcoal therapy of questionable value for acute salicylate poisoning. Controlled data demonstrating the clinical efficacy of this therapy are required to validate it as an intervention for this condition. PMID- 2191637 TI - [Allergy and psychosomatic disorders]. PMID- 2191638 TI - [Mesangioproliferative glomerulonephritis with IgM deposits as an independent form of nephritis]. AB - On the basis of 32 patients examination clinicomorphological characteristics of the mesangioproliferative glomerulonephritis (MPGN) with IgM deposits are given. The conclusion is drawn that MPGN is a distinct unity in the group of primary GN as well as in the group of IgM--nephropathy. The main pathogenetic component of the development of MPGN with IgM deposits is the fixation of IgM, especially in combination with C3. Moderate hypertrophy and hyperplasia of mesangiocytes, mesamgium enlargement and secondary changes in glomeruli characterize MPGN with IgM deposits electron-microscopically and light optically. MPGN with IgM deposits is followed by nephrotic syndrome in 3/4 cases although other clinical forms of nephritis can also take place. In most cases its clinical course is protracted and benign. PMID- 2191639 TI - [New approaches to the study of the pathological anatomy in diseases of fetal and neonatal periods]. AB - New forms of the pathology analysis are suggested to develop and introduce into the practice of pediatric pathologists in order to decrease the level of perinatal mortality in USSR: 1) the study of causes of death in children weighing from 500 to 999 g; 2) anatomopathological determination of the gestational period; 3) pathomorphology of transitional conditions in newborns; 4) early autopsies of foetuses and newborns, improving the reanimation pathology diagnosis; 5) the increase of the thoroughness in the study of placenta and reconsideration of the nosological approaches in the evaluation of the placenta pathology; 6) current etiological diagnosis of infectious diseases including HIV infections. PMID- 2191640 TI - [The functional anatomy of the pharynx, esophagus and trachea in adults and newborn infants]. PMID- 2191641 TI - [Surgical treatment of dysphagia of the pharyngoesophageal transition]. PMID- 2191642 TI - [Dysphagia from the neurologic viewpoint]. PMID- 2191643 TI - [Clinical aspects of pharyngoesophageal dysphagia from the otorhinolaryngologic viewpoint]. PMID- 2191644 TI - [Functional and electrophysiologic diagnosis of dysphagia]. PMID- 2191645 TI - [Manifestations of dysphagia from the internal medicine viewpoint]. PMID- 2191646 TI - The behavioral genetics of Caenorhabditis elegans. AB - Caenorhabditis elegans, a small free-living soil nematode, is an ideal organism for the genetic dissection of simple behaviors. Over 150 genes required for normal behavior have been identified. We review here the neural and genetic pathways underlying four of the best-studied C. elegans behaviors: locomotion, response to gentle touch, egg-laying, and chemotaxis. Mutations affecting these behaviors have identified genes which specify neuronal cell lineage, neuronal cell fate, and the formation of cell matrix cues involved in axonal guidance. Molecular analysis of genes required for normal behavior offers the prospect of characterizing functionally important nervous system proteins, regardless of their abundance or biochemical role. PMID- 2191648 TI - Who discovered the twin method? AB - The twin method is usually credited to Francis Galton's 1875 article on twins. However, Galton did not propose the comparison between identical and fraternal twin resemblance which is the essence of the twin method. Although the twin method was "in the air" in the mid-1920s, the first descriptions of the method appeared in an article by Curtis Merriman and in a book by Hermann Siemens, both in 1924, 50 years after Galton's paper. PMID- 2191647 TI - Molecular aspects of egg-laying behavior in Aplysia californica. AB - The Aplysia neuroendocrine system is a particularly advantageous model for cellular and molecular studies because of the relatively small number and large size of its component neurons. In addition, numerous anatomical and studies have resulted in the assignment of behavioral roles to individual identified neurons. Recombinant DNA techniques have been used to isolate the genes that encode the precursors of peptides involved in egg-laying behavior. The comparison of the egg laying hormone (ELH) gene family within the genus Aplysia reveals high homologies in the overall structure of the precursors. A well-conserved tetrabasic residue has been shown to be the first endoproteolytic cleavage site of the precursor, giving rise to two intermediates, which are differentially processed and packaged. Some members of the ELH gene family are expressed specifically in the bag cell clusters or the atrial gland, respectively, providing an opportunity to study control of gene expression at the molecular level. PMID- 2191649 TI - [Virus carriers in foot-and-mouth disease. Review]. AB - FMDV infection can cause a long lasting virus carrier state in the oesophageal pharyngeal (OP) region of cattle, sheep, goats, African buffalo, wildebeest and kudu. Virus can be recovered from OP fluids with low titres for several months up to more than 2 years. During this time phases of positive virus recovery are interrupted by negative phases. The number of virus carriers decreases as time progresses. The virus carrier state is always accompanied by FMDV antibodies in serum and OP fluid. Vaccinated animals also become virus carriers after FMDV infection, to the same extent as unvaccinated animals. No virus carrier state has been proven in pigs, but it cannot be excluded in some species of deer. Epizootic importance of carrier animals (in FMD) has not been found. Experimental contact transmissions of carrier virus to cattle, sheep and goats have failed. Only buffalo transmit carrier virus to the own species and perhaps to cattle. Nevertheless, virus carriers represent a natural reservoir of FMDV in infected areas and a potential source of antigenically altered virus variants, since continuous variations of the virus and selection of virus mutants take place in the animal during the carrier state. PMID- 2191650 TI - [Stress hyperglycemia in cats]. AB - It may be difficult to differentiate the possible causes of hyperglycemia in the cat. The following investigation was on transient hyperglycemia in 320 cats. The frequency and degree of stress-hyperglycemia and its relation to different types of primary diseases was proven. Animals with overt diabetes mellitus or pancreatic diseases were not included in this study. Plasma glucose was analyzed with the o-Toluidine- or with the glucose oxidase-method. Plasma immune-reactive insulin (IRI) was estimated by RIA. A glucose concentration of greater than or equal to 140 mg/dl (7.77 mmol/l) in the fasted animal was defined as hyperglycemia. The results of the retrospective investigation show in cats transient hyperglycemia occurs more often (3.2%) than permanent hyperglycemia (0.57%). Contrary to overt diabetes mellitus there is no sex- or age-related predisposition. Glucose values above 300 mg/dl (16.65 mmol/l) with maximal values up to 620 mg/dl (34.42 mmol/l) were estimated in 12% of the animals. In 12 from 19 hyperglycemic animals the basal IRI values were between 4 and 14 microU/ml, 11 animals had a lowered I/G ratio. In the following order of frequency the primary diseases found in combination with transient hyperglycemia were: dys- and stranguria, viral and bacterial infections, gastrointestinal diseases, neoplasia, renal insufficiency, cardiopathies etc. With improvement of the underlying disturbance the stress-related hyperglycemia normalized without insulin therapy within a few days. In conclusion, it is necessary to initially identify basic diseases that may trigger the onset of stress-hyperglycemia in the cat. Neither the extent of the glucose level nor a single plasma-insulin-value are valid indicators of confirming the diagnosis of diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2191651 TI - Clonal adaptation during carcinogenesis. PMID- 2191653 TI - The future of public health: prospects in the United States for the 1990s. PMID- 2191652 TI - Cyproheptadine-induced alterations in clonal insulin-producing cell lines. AB - Cyproheptadine (CPH) inhibits glucose-stimulated insulin synthesis and secretion, and reversibly depletes pancreatic insulin content in the rat. To examine whether the inhibitory actions of CPH on insulin cell function are linked to the ability of glucose to stimulate insulin synthesis and secretion, studies were performed in two different insulin-producing cell lines. CPH effects were compared in HIT T15 cells, which respond to glucose with increased insulin synthesis and secretion, and in glucose-unresponsive RINm5F cells. CPH produced similar alterations in both cells lines. After a 48-hr culture period in the presence of 0, 0.1, 1.0 or 10.0 microM CPH, cellular insulin stores and media insulin levels were decreased in a concentration-dependent manner. At 10.0 microM CPH, RIN and HIT cell insulin content declined to 34 and 33% of controls respectively. Cellular insulin returned to control levels 48 hr after removal of CPH. In experiments designed to test a direct inhibitory effect on stimulated insulin secretion, 1 and 10.0 microM concentrations of CPH were found to inhibit glucose stimulated insulin release from HIT cells, and K+, alanine and glyceraldehyde stimulated release from RIN cells. CPH was also shown to inhibit insulin biosynthesis in both cell lines at concentrations that did not alter the synthesis of total cellular proteins. All of these alterations in cellular function were shown to occur at CPH concentrations that did not affect cell growth or viability. The results show that the actions of CPH do not appear to be dependent upon the existence of operational glucose signalling mechanisms for insulin synthesis and secretion. PMID- 2191654 TI - Genetics and public health in the 1990s. PMID- 2191655 TI - HIV infections and AIDS in the 1990s. PMID- 2191656 TI - Prospects for cancer control in the 1990s. PMID- 2191657 TI - Measurement of health status in the 1990s. AB - The use of health-related quality of life measures, especially those based on function, are likely to increase during the next decade. This increase, however, is most likely to occur in clinical research and clinical practice. Unless the necessary political will, resources, data, and policy researchers coexist, there will be relatively little advance in the use of health status measures for decision-making and policy. This prediction is based on the observation that policy research tends to rely on available national data, that currently these data provide limited information about health status, and that there appears to be insufficient interest and resources to broaden data collection or to develop methods that incorporate a broad spectrum of health outcomes (e.g. death, impairment, functional status, and perceptions) into a single instrument or measure of health on large populations and communities. This state of affairs is particularly unfortunate as we face a decade in which available health and medical care may become more limited and social inequity in access and health status may become more marked. The effect of social inequities and restrictions to health care on the health of the nation cannot continue to be determined with reference only to the structure and process of the health care system. Health and quality of life outcomes are what count. And, these outcomes cannot be determined without appropriate and inclusive measures of health-related quality of life. Of course, we hope our prediction is wrong and that the motivation and resources will be found to help resolve methodologic issues in the measurement of population health status and quality of life and to provide the necessary data. We hope that government agencies, employers, and private providers will begin to collect health-related quality of life data on the constituents and populations they serve. Even if these data are imperfect or primitive, the effects of improving accessibility and quality of health care can only be assessed adequately in terms of the health-related quality of life of the nation. PMID- 2191658 TI - Child health in the United States: prospects for the 1990s. PMID- 2191659 TI - Geographic access to physician services. PMID- 2191660 TI - Setting objectives for public health in the 1990s: experience and prospects. PMID- 2191661 TI - Injury prevention and control: prospects for the 1990s. PMID- 2191662 TI - Chronic disease in the 1990s. PMID- 2191663 TI - Toxics and public health in the 1990s. PMID- 2191664 TI - Health promotion as a public health strategy for the 1990s. PMID- 2191665 TI - The health sector in developing countries: problems for the 1990s and beyond. PMID- 2191666 TI - Child labor in 1990: prevalence and health hazards. PMID- 2191667 TI - State approaches to financing health care for the poor. PMID- 2191668 TI - Public health policy for the 1990s. PMID- 2191669 TI - Health risk appraisal in the 1990s: opportunities, challenges, and expectations. PMID- 2191670 TI - Governmental regulation of environmental hazards in the 1990s. PMID- 2191671 TI - Nutrition: prospects for the 1990s. AB - For many decades there has been adequate information for the elimination of acute dietary deficiency diseases. Scurvy, beri-beri, and pellagra, once serious scourges, are now seen only rarely. The severe forms of protein-energy malnutrition, kwashiorkor and marasmus, have also decreased greatly. Nonetheless, mild to moderate forms of protein-energy deficiency, exacerbated by infection, continue to impair growth and development in a majority of the low-income pre school age populations of most developing countries. Deficiencies of iron, iodine, and vitamin A are still widespread in developing countries. Fortunately, the success of the WHO/UNICEF "Child Survival and Development Revolution" in persuading most developing countries to introduce expanded programs of immunization, growth monitoring, and appropriate feeding of young children, control of diarrheal disease, and specific campaigns against avitaminosis A, iodine deficiency disorders, and the functional consequences of iron deficiency, will accelerate the decline of acute deficiency diseases in the developing world. Diets are changing among the more affluent in these countries, however, and it is time for them to stress dietary goals for the health of rich and poor alike. For the first time there is enough information regarding dietary risk factors for chronic disease to provide an opportunity in the 1990s to accelerate the dietary changes that have already brought significant health benefits to some populations in North America and Europe. The changes, which include a lower dietary intake of fat, particularly saturated fat, less salt, and more green and yellow vegetable and whole grain cereals, can be expected to influence favorably morbidity from cardiovascular diseases and some kinds of cancer. For maximum benefit, these measures need to be combined with the avoidance of obesity, reasonable physical activity, abstention from, or moderate use of, alcohol, and avoidance of tobacco in any form. Since there is already considerable momentum toward these changes in North America and some European countries, the 1990s are likely to see substantial further progress in the reduction of chronic diseases known to be influenced by diet. PMID- 2191672 TI - Toxic substances control in the 1990s: are we poisoning ourselves with low-level exposures? PMID- 2191673 TI - Occupational health in the 1990s. AB - Where have we come since the Occupational Safety and Health Act was passed in 1970? Have we made progress in this country toward "safe and healthful working conditions for working men and women?" Many hazardous exposures that were prevalent before the creation of NIOSH, OSHA, and MSHA have been reduced. Exposure to asbestos, coal dust, silica, lead, and cotton dust are common examples. Through OSHA's Hazard Communication Standard and state Right to Know laws as well as an increase in the dissemination of information, the average employer and worker today is better informed of specific hazards on the job, and more attentive to safety measures. However, the high toll of work related disease and injuries continues today. PMID- 2191674 TI - Blood flow: insights from ultrasound. AB - Ultrasonic pulse-echo systems can provide range-finding, time-position and real time two-dimensional images of soft-tissue structures within the body. The Doppler effect can be used to study motion and blood flow. Continuous wave Doppler instruments provide information about velocity and direction of flow; depth discrimination can be obtained by pulsing the ultrasound. Two-dimensional Doppler flow imaging can be achieved by manual scanning of a probe over the skin surface. The combination of real-time pulse-echo imaging with pulsed Doppler blood flow detection in the duplex scanner makes it possible to localize the anatomical position of the Doppler sample volume. Real-time Doppler colour flow imaging combines traditional ultrasonic scanning with a two-dimensional flow map. Using appropriate ultrasonic instruments, blood flow volume rates, blood flow velocity profiles, pressure gradients, orifice areas, flow disturbances, jets, characteristics of blood vessels and the circulatory system, and tissue perfusion can all be investigated. These investigations have clinical applications in the study of cardiac, cerebral and peripheral blood flow, blood flow in the female pelvis, the fetus, the abdomen, the neonate, and in malignant tumours. Contemporary ultrasonic diagnosis employs exposure levels that are apparently free from biological risk, but other factors need to be taken into account in considering the prudent use of ultrasonic methods. Promising research is being carried out into the mechanism of ultrasonic scattering by blood, Doppler speckle, time-domain processing for blood flow imaging, methods for increasing the scanning speed, Doppler flow microscopy and contrast agents. The new technology that will result from this research should lead to further substantial progress in ultrasonic blood flow studies. PMID- 2191675 TI - [Suppression of lymphocyte function 2 years following surgical treatment of paranasal sinus mycosis]. AB - Prior investigations showed that acutely diseased patients with an aspergillus sinusitis manifested immune dysfunctions in respect of both T and B lymphocytes. In contrast to patients with nonmycotic sinusitis reduced in vitro and in vivo responsiveness was observed. The aim of this study, carried out after removal of the fungus ball and endoscopic surgery in clinically healthy patients, was to ascertain whether this reduced responsiveness was to be regarded as the effect or cause of an Aspergillus fumigatus infection. Two years later, the in vivo response to recall antigens was normal in both groups of patients, whereas the response to mitogens (ConA, PHA and PWM) was still decreased in the aspergillus sinusitis groups. The data suggest that the reduced immune response is a consequence of the Aspergillus fumigatus infection. Depressed skin reactivity is only present during acute infection, while proliferative capacity, as measured in the "whole blood stimulation" assay is depressed for a long time after healing the acute infection. PMID- 2191676 TI - [Myofunctional disorders of the orofacial region in childhood. Clinical aspects- etiology--therapy]. AB - The differential diagnosis of myofunctional, articulational and specific ENT disorders is a phoniatric domain. The symptoms of orofacial dysfunctions are presented and aetiological factors of myofunctional disorders of the orofacial region are discussed for children. In many cases the surgery of ENT-disorders (e.g. adenotomy, tonsillectomy, frenulotomy) makes favorable conditions for logopedic oriented myofunctional therapies according to the age. PMID- 2191677 TI - [How can hyperreflexia rhinopathy be modified surgically? I. Literature review]. AB - A review of the literature on the surgery of vasomotor rhinitis revealed only a few studies with information by which to judge the value of a special surgical method, especially concerning its long-term results. The following modalities of treatment were reviewed: submucous resection of the septum (Killian), Vidian neurectomy, conchal surgery (diathermy, partial and total turbinectomy, cryosurgery, laser-surgery). As far as information is available, advantages and shortcomings of individual methods are listed in tables. Partial turbinectomy seems to be most effective in reducing nasal obstruction without damaging nasal functions. Nasal hypersecretion is not sufficiently influenced by the cited surgical methods. In the authors' hospital, conchal surgery is performed in about sixty percent of all nasal operations. Gray's method of anterior turbinoplasty of the inferior turbinate is used. PMID- 2191678 TI - [Squamous cell carcinoma-associated antigen (SCC) as a tumor marker in the initial diagnosis of carcinomas of the head and neck region. Results of a prospective study after 24 months]. AB - The serum--SCC antigen levels of patients with head and neck tumors were studied prospectively to determine their value in the initial diagnosis of head- and neck cancer patients. Serum concentrations above 2 ng/ml are considered abnormal. Preliminary results of the study after a 12-month period have been reported elsewhere (1). The final results of the study show an increased percentage (53%) of pathologic findings, mostly due to the increasing number of advanced stage tumors. High serum levels were found in 60% of the T4-tumors (Fig. 4a). Well differentiated carcinomas seem to be associated with the antigen more frequently than poorly differentiated tumors (Fig. 5). SCC antigen levels were examined as many as five times before the start of treatment (85 patients), and in one-third of those cases the differences between the serum levels exceeded 1 ng/ml. As far as 85% specificity is concerned, the ROC-curve shows a sensitivity of only 40% (Fig. 2) which, in addition to the fact that the antigen was most frequently found in cases of advanced tumors, indicates that the usefulness of the SCC antigen as a tumor marker for head and neck cancer must still be regarded as low. PMID- 2191679 TI - Physician supply in the United States 1980-1988. A select bibliography commissioned for the task force on physician supply of the Association of American Medical Colleges. PMID- 2191680 TI - Problems in the investigational study and clinical use of cancer immunotherapy. AB - The last decade has witnessed a veritable explosion in the investigational study and clinical use of immunotherapy for the treatment of cancer. Although this is an exciting development, the promise of cancer immunotherapy has not yet been fulfilled. Why is there an apparent discrepancy between the theory of cancer immunotherapy and the actual results from clinical studies? Michael Osband and Susan Ross suggest that there are several basic problems with the clinical study and therapeutic use of immunotherapy that must be overcome before it can be considered a viable treatment for a broad range of tumors. The purpose of this article is to describe some of the more important of these problems. PMID- 2191681 TI - Lymphokine gene therapy for cancer. AB - The plethora of recombinant lymphokines that have recently become available has led to renewed hope for an immunotherapeutic solution to cancer. Many lymphokines, either singly or in combination, have already shown promise in animal trials and in preliminary human trials. Systemic lymphokine toxicity has been the major constraint on this type of therapy, often precluding the use of doses sufficient to induce tumour regression. To realize the therapeutic potential of recombinant lymphokines against cancer, alternative modes of delivery are needed which maximally stimulate local anti-tumour responses whilst causing minimal systemic toxicity. In this article, Stephen Russell proposes that tumour cell targeted lymphokine gene therapy would optimize lymphokine delivery. Some of the practical difficulties likely to be encountered with such an approach are also discussed. PMID- 2191683 TI - Is T-cell memory maintained by crossreactive stimulation? AB - Whether or not T- and B-cell memory is antigen driven remains unresolved. Recent studies indicate that, in humans, naive and memory T cells can be distinguished by their expression of different CD45 isoforms. Extensive phenotypic analysis of naive and memory T cells shows that the latter express greater amounts of several adhesion molecules as well as low levels of several antigens indicative of activation. These features suggest to Peter Beverley that memory T cells may be more readily activated and that memory may be maintained by crossreactive restimulation. PMID- 2191682 TI - Cytokines and Ig switching: evolutionary divergence between mice and humans. AB - Cytokines exert control over many aspects of immunoglobulin regulation, including isotype switching. But is the same mechanism used in subclass regulation in mice and humans? Robin Callard and Malcolm Turner think not, and here caution against the wholesale application of murine studies to humans. PMID- 2191684 TI - Mechanisms of dendritic cell function. AB - There is now considerable evidence, from in vivo and in vitro studies, supporting the claim that dendritic cells are the principal accessory cells of the vertebrate immune system. Until recently, however, the biology of the dendritic cell accessory mechanism has remained obscure. Here, Philip King and David Katz review recent findings that have clarified several aspects of this mechanism, providing a possible basis for the potent T-cell stimulating capacity of the dendritic cell, and yielding clues to the ontogenetic relationships of these cells and to their role in immunopathology. PMID- 2191685 TI - Macrophages and the human immunodeficiency virus. PMID- 2191686 TI - [Asthma: physiopathology]. AB - Physiopathological components of asthmatic disease are the fundamentals of present therapeutic research on asthma. It is never certain what is the primary event. Better understood are the effects of the mediators. At the anatomic level, the following are always found: hyperplasia of smooth muscle, inflammatory infiltration by polynuclear eosinophils and glandular hypertrophy with hypersecretion. Immunology will be considered separately. PMID- 2191687 TI - [Clinical diagnosis of asthma]. AB - Paroxysmal wheezing dyspnea, asthma may evolve from a simple crisis to an asthmatic attack that repeats several crises daily with duration up to several weeks, in some months when the asthmatic illness becomes life-threatening. Chronology of asthma is related to bronchial inflammation without knowing how to avoid the development of complications. Childhood types and those of subjects of more than 65 years are well characterised by mechanisms of bronchial hyper reactivity that are always found and are identical to the type found in young adults. There are "limited" types that need respiratory function tests for confirmation of asthma. PMID- 2191688 TI - [Functional respiratory diagnosis]. AB - The timing of the examination is an important stage in recognising asthma and its repercussion on haematosis. It consists of exploring the broncho-mototricity and of evaluation of the effect of asthma on ventilation and gas exchange. Respiratory function tests contribute additional information to the clinical history, and etiology and to the decision of therapy strategy. PMID- 2191690 TI - Animal models for intranasal drug delivery studies. A review article. AB - The purpose of this review is to introduce the investigators to sources of information and to guiding principles regarding the choice of animal models for experimental and clinical studies on intranasal application studies. It focuses also on the anatomical and physiological variations that can influence the selection of the correct animal model. A topical overview is given for following animal models which are all involved in intranasal drug or vaccine delivery research; dog, guinea pig, hamster, mouse, rabbit (in vivo and in situ), rat (in vivo, in vivo surgical and in situ) and sheep. In the selection of an animal model, both advantages and disadvantages must be considered. Small animals such as guinea pigs, hamsters, mice and rats, are easy to handle and inexpensive, but their nasal cavity is small and therefore preferred for absorption studies and for studying the influence of absorption promoters. Dogs, monkeys, sheep and rabbits are particularly useful in pharmacokinetic and formulation studies. PMID- 2191689 TI - [The etiologies of asthma]. AB - Asthma may have several etiologies. It is well-known that there are allergic subjects with low IgE bound to mast cells, with negative specific RAST and with weakly positive skin tests, but with a positive provocation test with pneumo allergens. Food allergy, isolated or associated is also not a negligible cause. Non-allergic subjects often respond to triggering factors: Gastro-oesophageal reflux Neuro-endocrine origin Infectious origin Physical origin (exercise). In our study, we place the emphasis on two types of extremely severe asthma, linked to intolerance of aspirin and metabisulphites and often associated. PMID- 2191691 TI - Soil remediation techniques at uncontrolled hazardous waste sites. A critical review. AB - The objective of this critical review is to address soil remediation techniques at uncontrolled hazardous waste sites with regard to the following areas: 1) important regulatory and technical issues and information needs concerning soil remediation at uncontrolled hazardous waste sites; 2) approaches for selection of remediation techniques; and 3) the current state of knowledge regarding soil remediation techniques, including applications and limitations. The areas identified above are addressed with regard to current information, selected milestone publications, and specific applications of technologies to provide a synthesis of the topic. The information concerning current issues, approaches, and soil remediation techniques presented was critically reviewed in order to: 1) identify deficiencies in current approaches; 2) develop a conceptual framework for remediation; and 3) recommend improved approaches for selection of remediation technologies. PMID- 2191692 TI - The pathology of Shigella flexneri infection in rhesus monkeys: an endoscopic and histopathological study of colonic lesions. AB - Twenty-two Rhesus monkeys were orally fed 1 x 10(11) live virulent Shigella flexneri of either serotypes 1b, 2a, 4a or Y. On the basis of colonoscopic findings they were classified into: group A - normal endoscopic picture (10 monkeys), and group B - pathological endoscopic picture (12 monkeys). Pathological findings, distributed over the entire colon, were seen as either red patches (+/- erosions) or diffuse lesions, i.e. fragile red mucosa, mucosal bleeding and broad edemas. Histopathological examination of concomitant biopsies showed an acute inflammation restricted to the mucosa in 8/12 of group B as compared to 2/10 of group A. The Shigellae were most commonly demonstrated in the surface epithelium and more rarely in the deep layer of the lamina propria. Immunohistochemical staining, using monoclonal antibodies directed against Shigella flexneri O-antigenic polysaccharide, showed a high correlation with histopathological findings. Clinically all 10 monkeys in group A remained healthy, whereas 7/12 (all displaying histopathological signs of acute inflammation) in group B developed dysenteric symptoms. Colonoscopy should be combined with histopathological and immunohistochemical examinations of biopsies to study the pathological events taking place in the colon tissue during the course of a Shigella infection and will be of great value to assess the protective efficacy of S. flexneri vaccine candidates. PMID- 2191694 TI - Binding of bacteria to carbohydrates immobilized on beads to demonstrate the presence of cell-associated hemagglutinins in Vibrio cholerae. AB - We describe a phase contrast microscopy method for direct observation of classical and El Tor vibrios to agarose beads containing covalently attached L fucose or D-mannose. Binding of the vibrios to L-fucose beads was found to correlate with fucose-sensitive agglutination of human O erythrocytes, while binding of bacteria to beads with D-mannose was consistent with mannose-sensitive agglutination of chicken erythrocytes. Furthermore, vibrios expressing both fucose and mannose-sensitive hemagglutinins adhered equally to L-fucose and D mannose-containing beads. Because this procedure is neither subject to biological variations in different populations of erythrocytes nor affected by other factors known to interfere with hemagglutination tests, it offers a suitable, more robust and specific alternative to detect functional adhesins in Vibrio cholerae and other bacteria. PMID- 2191693 TI - Studies on beta-lactamases from Escherichia coli isolated from urinary tract infections. AB - The beta-lactamase types present in 75 ampicillin and carbenicillin resistant E. coli were characterized using isoelectric focusing (IEF). The strains were isolated from patients with urinary tract infections from two geographically different areas of Denmark: 38 strains from Copenhagen and 37 strains from North Jutland. For 19 of the strains from Copenhagen and 18 of the strains from North Jutland, their beta-lactamase activity against nitrocefin and ampicillin, carbenicillin, benzylpenicillin, cloxacillin and cephaloridine was examined by a micro-iodometric and an UV-spectrophotometric assay. The strains from Copenhagen showed greater activity (p less than 0.001) against nitrocefin than the strains from North Jutland. The rate of hydrolysis of ampicillin was greater for the strains from Copenhagen than for the strains from North Jutland. Ninety-three per cent of the strains produced plasmid-mediated beta-lactamases, of which the most prevalent, TEM-1, was produced by 97 per cent of these strains, and OXA-1 by 3 per cent. PMID- 2191695 TI - Ornithine decarboxylating strains of Klebsiella pneumoniae demonstrated by DNA DNA hybridization. AB - Genotypic relatedness was assessed to clarify the taxonomic position of strains phenotypically behaving like K. pneumoniae, but for the ornithine reaction. Using DNA-DNA hybridization it could be shown that 25 non-motile ornithine decarboxylating strains showed high genotypic relatedness to the type strain of K. pneumoniae. Thus, it is proposed that they be considered as ornithine decarboxylating strains of the species K. pneumoniae. The API 20E system was used for phenotypic characterization, but the API code obtained by these strains was not registered in the API Profile Index. However, except for the ornithine reaction the isolates behaved as typical K. pneumoniae. Three ornithine negative strains of E. aerogenes were identified as K. pneumoniae by the API 20E System, but they showed high genotypic relatedness to the type strain of E. aerogenes. PMID- 2191696 TI - The transitional circulation: physiology and anesthetic implications. AB - Over the past decade, several aspects of the physiology of the transitional circulation have been elucidated. The transitional circulation may be viewed as a process divided into four phases. The concept of these phases underscores the fact that the normal transitional circulation should be viewed as an orderly process and not a single event. Within these phases, several mechanisms seem to be involved in the control of pulmonary vascular resistance (PVR). Yet even these mechanisms do not completely explain the process of the normal transition, and very little is understood about why the transition occasionally fails. No doubt other as yet undescribed mechanisms also play a role. Much work remains to be done in the study of the normal and abnormal transitional circulation. The profound hypoxia that characterizes infants with failed transitional circulation from any cause is due to a persistently high PVR, causing right-to-left shunting at the ductal and foramental levels. Clinical care of these infants is based on efforts to simultaneously decrease PVR and increase systemic vascular resistance (SVR). Appropriate measures include the use of supplemental oxygen, hyperventilation, alkalinization, and sedation to decrease PVR and intravenous (IV) fluids and pressors to increase SVR. The rapidly fluctuating nature of the physiologic processes that cause failure of the transitional circulation must be kept in mind when caring for these infants, both during initial stabilization in the delivery room and while administering anesthesia for surgical repair of congenital defects. PMID- 2191697 TI - Asystole following neostigmine administration during carotid sinus stimulation. PMID- 2191698 TI - Chemical and photochemical probing of DNA complexes. AB - An overview of the chemical and photochemical probes which over the past ten years have been used in studies of DNA/ligand complexes and of non-B-form DNA conformations is presented with emphasis on the chemical reactions of the probes with DNA and on their present 'use-profile'. The chemical probes include: dimethyl sulfate, ethyl nitroso urea, diethyl pyrocarbonate, osmium tetroxide, permanganate, aldehydes, methidiumpropyl-EDTA-Fell (MPE), phenanthroline metal complexes and EDTA/FeII. The photochemical probes that have been used include: psoralens, UVB, acridines and uranyl salts. The biological systems analysed by use of these probes are reviewed by tabulation. PMID- 2191699 TI - [Radical correction of tetralogy of Fallot in infants under 1 year of age]. AB - The article generalizes the experience in surgical treatment of Fallot's tetrad in 20 infants. Radical correction of the anomaly was carried out under extracorporeal circulation and deep hypothermia with reduced volume rate of perfusion. Plastics of the conus arteriosus alone was performed in 6 patients, transanulus and the pulmonary trunk in 4 patients. Two patients died, the hospital lethality was 10%. A clinical effect was produced in all the other patients. The relation of systolic pressure in the left ventricle to that in the right ventricle was 0.56 +/- 0.1, the systolic pressure gradient between the right ventricle and the pulmonary artery was 18 +/- 4.2 mm Hg. Various degree of regurgitation at the pulmonary valve was revealed after the operation in all patients. It was maximum (34 +/- 10%) in transanulus plastics. PMID- 2191700 TI - [Foreign bodies in the lungs and pleura after intrathoracic surgical interventions (clinico-anatomical parallels)]. AB - Clinicoanatomical analysis of 6 cases of pathological processes in the lungs and pleura caused by gauze cloths left carelessly during operative treatment of pulmonary diseases was carried out. It was found that the character of these accidentally induced sufferings depended on the volume of the surgical intervention and the time during which the foreign bodies remained in the pleural cavity or the operative wound. The complications caused by the presence of gauze cloths accidentally left in the pleural cavity or lung follow a course separately from the initial pulmonary pathological process, have no pathogenetic relations to it, and possess a characteristic clinicoanatomical picture which allows them to be evaluated as surgical iatrogenesis, an equivalent of a nosological unit. PMID- 2191701 TI - [Myocardial revascularization]. PMID- 2191703 TI - [A new method of mitral valve prosthesis subvalvular structures of the anterior cusp]. PMID- 2191704 TI - [Surgical treatment of congenital aneurysm of the sinus of Valsalva]. PMID- 2191702 TI - [Simultaneous surgical correction of Ebstein's anomaly and ectopic supraventricular tachycardia]. PMID- 2191705 TI - 1965-1990: 25th anniversary of nurse practitioners. A classic manuscript reprinted in celebration of 25 years of progress. PMID- 2191706 TI - Anaesthesia and upper respiratory tract infections--a non-existent hazard? PMID- 2191707 TI - Some physiological and clinical aspects of chest physiotherapy. PMID- 2191708 TI - Inhalation anaesthetics and invertebrates. PMID- 2191709 TI - Antigen-presenting cells in the skin and placenta in pemphigoid gestationis. AB - In pemphigoid gestationis (PG), one of the major initiating events is the aberrant expression of the class II molecules of the major histocompatibility complex in the placenta. We used a panel of 13 monoclonal antibodies to investigate the phenotype of the MHC class II positive antigen-presenting cells (APC) in the skin and placenta in PG. In the skin, the APC show reactivity with a variety of macrophage markers and the CDI marker of Langerhans cells. By contrast, the MHC class II positive cells in the placenta showed no reactivity with macrophage or Langerhans cell markers, but were the cytokeratin-positive trophoblast or vimentin-positive stromal cells. PMID- 2191710 TI - Keratitis, ichthyosis and deafness (KID)-syndrome: report of three cases and a review of the literature. AB - We report three patients with keratitis, ichthyosis and deafness (KID)-syndrome. All had characteristic hyperkeratotic skin lesions and neurosensory hearing defects. Two had ophthalmologic symptoms. The third patient did not have eye involvement at the age of 3 years, but exhibited the other typical signs of the syndrome. In none of the three cases were any of the patients' relatives affected, and a spontaneous new mutation is the most likely explanation for the occurrence of this rare syndrome. Histopathological and electron microscopic studies revealed orthohyperkeratosis but no other pathology and no abnormal deposits of glycogen were found. Treatment with the aromatic retinoid etretinate proved to be of little value in any of the patients. The necessity for early audiologic and ophthalmologic evaluation and the need for life-long medical care for patients with KID-syndrome is emphasized. PMID- 2191711 TI - Convergence excess esotropia treated surgically with fadenoperation and medical rectus muscle recessions. AB - Convergence excess esotropia has been treated with bifocals, miotics, medial rectus recession(s), fadenoperation, or a combination of these. However, comparatively few studies on the sensory status of these patients exist. We present the sensory findings in 31 children treated surgically. Twenty-one had fadenoperations combined with bimedial rectus recessions, one had a fadenoperation alone, and nine had augmented bimedial rectus recessions. Five children (16%) achieved bifoveal fusion, 22 (71%) had varying degrees of peripheral fusion, and four (13%) had no detectable binocularity after a mean postoperative follow-up of 2.4 years. PMID- 2191712 TI - A comparison of local and systemic acyclovir in the management of herpetic disciform keratitis. AB - Forty-three patients with active herpetic disciform keratitis were entered into an open study to compare the efficacy of oral acyclovir (400 mg) with acyclovir ophthalmic ointment (3%) to inhibit viral replication during treatment with 0.05% prednisolone eye drops. All patients, regardless of the mode of therapy, were treated five times a day until they were healed. The mean time to heal in the oral group was 25.9 days and in the topical group was 25.3 days. Resolution of lacrimation was significantly faster in the oral group (12.1 days versus 27.6 days). The patients on tablets also showed a greater improvement in visual acuity. No statistically significant differences were found between the two groups in the incidence of recurrences over a three-year post-treatment period. It is concluded that oral acyclovir treatment is an effective alternative to ophthalmic ointment in the management of herpetic disciform keratitis. PMID- 2191713 TI - Optic nerve hypoplasia in children. AB - Optic nerve hypoplasia (ONH) is characterised by a diminished number of optic nerve fibres in the optic nerve(s) and until recently was thought to be rare. It may be associated with a wide range of other congenital abnormalities. Its pathology, clinical features, and the conditions associated with it are reviewed. Neuroendocrine disorders should be actively sought in any infant or child with bilateral ONH. Early recognition of the disorder may in some cases be life saving. PMID- 2191715 TI - Synthesis and distribution of primer RNA in nuclei of CCRF-CEM leukemia cells. AB - The distribution of primer RNA and RNA-primed nascent DNA in nuclei of CCRF-CEM leukemia cells was examined, and the primer RNA purified from the nuclear matrices of these cells was characterized. RNA-primed nascent DNA was radiolabeled by incubating whole-cell lysates with [alpha-32P]ATP and [3H]dTTP in the presence of approximately physiological concentrations of the remaining ribo- and deoxyribonucleoside triphosphates. The primer RNA was purified by cesium chloride density gradient centrifugation and analyzed by polyacrylamide gel electrophoresis. Nuclear subfractionation studies revealed that at least 94% of the primer RNA and RNA-primed nascent DNA were located within the insoluble matrix fraction of the nucleus. The predominant primer RNA isolated from the nuclear matrix was 8-10 nucleotides in length, and several lines of evidence indicated that this oligoribonucleotide was the functional primer RNA. Essentially all of the matrix primer RNA was covalently linked to the newly replicated DNA as demonstrated by its buoyant density in cesium chloride gradients, phosphate-transfer analysis, and sensitivity to DNase I. Analysis of 32P transfer from [alpha-32P]dTTP revealed a random distribution of ribonucleotides at the 3'-end of the primer RNA. Data obtained from mixing experiments indicated that the association of RNA-primed nascent DNA with the nuclear matrix was not the result of aggregation of these fragments with the nuclear matrix. No significant amount of either primer RNA, RNA-primed nascent DNA, or phosphate transfer was detected in the high-salt-soluble (nonmatrix) fraction of the nucleus, although the nonmatrix fraction contained most of the newly replicated DNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2191714 TI - Colour Doppler imaging in the demonstration of an orbital varix. AB - Colour Doppler imaging (CDI) is a recent development in ultrasonography. It allows simultaneous two-dimensional structural imaging and Doppler evaluation of blood flow. Quantitative information on flow velocity is obtained by pulsed Doppler spectral analysis, the colour information being used to choose the vessel of interest. Using this technique the authors examined a patient with an orbital varix previously diagnosed by clinical findings and computed tomography. Dynamic evaluation with real-time direct imaging of flow facilitated the diagnosis of this orbital disorder without the need for any contrast material. This technique may prove to be a useful adjunct to computed tomography for the evaluation of suspected vascular lesions of the orbit. PMID- 2191716 TI - Reconstitution of Escherichia coli 50S ribosomal subunits containing puromycin modified L23: functional consequences. AB - In previous work we have shown that both puromycin [Weitzmann, C. J., & Cooperman, B. S. (1985) Biochemistry 24, 2268-2274] and p-azidopuromycin [Nicholson, A. W., Hall, C. C., Strycharz, W. A., & Coooperman, B. S. (1982) Biochemistry 21, 3809-3817] site specifically photoaffinity label protein L23 to the highest extent of any Escherichia coli ribosomal protein. In this work we demonstrate that L23 that has been photoaffinity labeled within a 70S ribosome by puromycin (puromycin-L23) can be separated from unmodified L23 by reverse-phase high-performance liquid chromatography (RP-HPLC) and further that puromycin-L23 can reconstitute into 50S subunits when added in place of unmodified L23 to a reconstitution mixture containing the other 50S components in unmodified form. We have achieved a maximum incorporation of 0.5 puromycin-L23 per reconstituted 50S subunit. As compared with reconstituted 50S subunits either containing unmodified L23 or lacking L23, reconstituted 50S subunits containing 0.4-0.5 puromycin-L23 retain virtually all (albeit low) peptidyl transferase activity but only 50-60% of mRNA-dependent tRNA binding stimulation activity. We conclude that although L23 is not directly at the peptidyl transferase center, it is sufficiently close that puromycin-L23 can interfere with tRNA binding. This conclusion is consistent with a number of other experiments placing L23 close to the peptidyl transferase center but is difficult to reconcile with immunoelectron microscopy results placing L23 near the base of the 50S subunit on the side facing away from the 30S subunit [Hackl, W., & Stoffler-Meilicke, M. (1988) Eur. J. Biochem. 174, 431 435]. PMID- 2191717 TI - NMR study of the phosphoryl binding loop in purine nucleotide proteins: evidence for strong hydrogen bonding in human N-ras p21. AB - The structure of the phosphoryl binding region of human N-ras p21 was probed by using heteronuclear proton-observed NMR methods. Normal protein and a Gly-12--- Asp-12 mutant protein were prepared with two amino acids labeled with 15N at their amide positions: valine and glycine, aspartic acid and glycine, and lysine and glycine. We completed the identification of amide 15NH resonances from Gly-12 and Asp-12 to the end of the phosphoryl binding domain consensus sequence (Lys 16) in protein complexed with GDP and have made tentative amide identifications from Val-9 to Ser-17. The methods used, together with initial identifications of the Gly-12 and -13 amide resonances, were described previously [Campbell-Burk, S. (1989) Biochemistry 28, 9478-9484]. The amide resonances of both Gly-13 and Lys 16 are shifted downfield below 10.4 ppm in both the normal and mutant proteins. These downfield shifts are presumed to be due to strong hydrogen bonds with the beta-phosphate oxygens of GDP. PMID- 2191718 TI - Aluminum fluoride inhibition of glucocorticoid receptor inactivation and transformation. AB - Fluoride, in the presence of aluminum ions, reversibly inhibits the temperature mediated inactivation of unoccupied glucocorticoid receptors in cytosol preparations from mouse L cells. The effect is concentration-dependent, with virtually complete stabilization of specific glucocorticoid-binding capacity at 2 mM fluoride and 100 microM aluminum. These concentrations of aluminum and fluoride are ineffective when used separately. Aluminum fluoride also stabilizes receptors toward inactivation by gel filtration and ammonium sulfate precipitation. Aluminum fluoride prevents temperature-dependent transformation of steroid-receptor complexes to the DNA-binding state. Aluminum fluoride does not inhibit calf intestine alkaline phosphatase, and unoccupied receptors inactivated by this enzyme in the presence of aluminum fluoride can be completely reactivated by dithiothreitol. The effects of aluminum fluoride are due to stabilization of the complex between the glucocorticoid receptor and the 90-kDa mammalian heat shock protein hsp90, which suggests that aluminum fluoride interacts directly with the receptor. Endogenous thermal inactivation of receptors in cytosol is not accompanied by receptor dephosphorylation. However, inactivation is correlated with dissociation of hsp90 from the unoccupied receptor. These results support the proposal that hsp90 is required for the receptor to bind steroid and dissociation of hsp90 is sufficient to inactivate the unoccupied receptor. PMID- 2191719 TI - In vitro and in vivo activities of T4 endonuclease V mutants altered in the C terminal aromatic region. AB - Genes encoding mutants of the thymine photodimer repair enzyme from bacteriophage T4 (T4 endonuclease V) having an amino acid substitution (T127M, W128A, W128S, Y129A, K130L, Y131A, Y132A) were constructed by use of a previously obtained synthetic gene and expressed in Escherichia coli under the control of the E. coli tryptophan promoter. An in vitro assay of partially fractionated mutant proteins for glycosylase activity was performed with chemically synthesized substrates containing a thymine photodimer. T127M and K130L showed almost the same activity as the wild-type protein. Although W128S, Y131A, and Y132A were slightly active, W128A and Y129A lost activity. The results indicated that the aromatic amino acids around position 130 may be important for the glycosylase activity. Mutant T127M was purified, and the Km value was found to be of the same order as that of the wild type (10(-8) M). In vivo activities for all mutants were characterized with UV-sensitive E. coli. The results showed that substitution of Thr-127 with Met or Lys-130 with Leu did not have an effect on the survival of the bacteria but substitution of aromatic amino acids (128-132) had various effects on survival. PMID- 2191720 TI - Importance of residues Arg-167 and Gln-231 in both the allosteric and catalytic mechanisms of Escherichia coli aspartate transcarbamoylase. AB - Site-specific mutagenesis has been used to create two mutant versions of aspartate transcarbamoylase. Arg-167 and Gln-231, both previously identified as interacting with the portion of the bisubstrate analogue N-(phosphonoacetyl)-L aspartate (PALA) that corresponds to aspartate [Krause, K. L., Voltz, K. W., & Lipscomb, W. N. (1987) J. Mol. Biol. 193, 527-553], were replaced by glutamine and leucine, respectively. The Arg-167----Gln and the Gln-231----Leu enzymes show approximately 900-fold and 1500-fold reductions in the maximal observed specific activity, respectively. The aspartate concentration at half the maximal observed specific activity is increased 18-fold for the Gln-231----Leu enzyme compared to the value for the wild-type enzyme, but is altered little in the case of the Arg 167----Gln enzyme. The carbamoyl phosphate concentration at half the maximal activity is unchanged by either mutation, suggesting that these mutations result in only local changes to the aparatate binding site. Both mutations eliminate homotropic cooperativity; however, the Gln-231----Leu enzyme also has altered heterotropic interactions and no longer exhibits substrate inhibition. At relatively low concentrations of aspartate and saturating carbamoyl phosphate, PALA is able to activate the Gln-231----Leu enzyme, whereas the Arg-167----Gln enzyme is inhibited at PALA concentrations that normally activate the wild-type enzyme. Equilibrium binding measurements indicate that the Gln-231----Leu enzyme binds CTP approximately 10-fold more weakly than the wild-type enzyme, even though the mutation is some 70 A from the regulatory binding site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2191721 TI - Immune response of rabbits to native G-actins. AB - Actins are highly conserved proteins and are therefore claimed to be not very immunogenic without prior denaturation or chemical modification. We have obtained in rabbits high-titered antibodies to "native" G-actins from chicken and man, and assayed their cross-reaction using an enzyme immunoassay, Western blotting and immunohistochemistry. The antigens differ in their ability to induce antibody formation (chicken gizzard actin [(beta), gamma] greater than chicken skeletal actin [alpha] = human platelet actin [beta, (gamma)]). Antibodies to skeletal actin [alpha] are muscle-specific and mainly directed against the homologous region comprising the N-terminus (residues 1-226). Antibodies to gizzard actin [(beta), gamma] cross-react, to a lesser extent, with the alpha and beta, (gamma) isoforms. They show no regional specificity within the homologous antigen. Antibodies to the tryptic core fragment (residues 69-374) of skeletal actin react with fragments comprising the C-terminal part of muscular actins. Antibodies to platelet actin [beta, (gamma)] cross-react with muscular actins, recognizing not the native, but slightly degraded molecules. Platelet actin induces the formation of high-titered albumin antibodies for hitherto unknown reasons. PMID- 2191722 TI - Elegantin and albolabrin purified peptides from viper venoms: homologies with the RGDS domain of fibrinogen and von Willebrand factor. AB - The RGD-containing peptides isolated from the venoms of the Viperidae constitute a new class of small cysteine-rich peptides of variable amino acid composition and biological activity (Huang, T.-F., et al. (1987) J. Biol. Chem. 262, 16157 16163; Gan, Z.R., et al. (1988) J. Biol. Chem 263, 19827-19832; Huang, T.-F., et al. (1989) Biochemistry 28, 661-668), which it is proposed by Gould et al. (unpublished data) that we call 'disintegrins'. These peptides bind to the glycoprotein IIb-IIIa receptor on the platelet surface and inhibit aggregation induced by ADP, thrombin, platelet-activating factor and collagen. These peptides are also potent inhibitors of cell adhesion to fibrinogen (Knudsen, K.M., et al. (1988) Exp. Cell Res. 179, 42-49). We report the isolation of two further RGD peptides from the venoms of Trimeserusus elegans and Trimeserusus albolabris, purified to homogeneity with high yield by a novel, rapid reverse-phase HPLC method. The primary structures of these two peptides were determined to be single polypeptide chains of 73 amino acids. Albolabrin differed from trigramin by eight residues whilst elegantin differed by 22 residues. The molecular mass of albolabrin calculated on the basis of amino acid sequence was 7574 Da and the pI similarly calculated was 4.27. The molecular mass of elegantin was calculated to be 7806 Da and the theoretical pI to be 4.69. RGD is maintained in the same position (51-53 AA) and all 12 cysteines are identical. Our data suggest that the presence of RGD, the conserved secondary and tertiary structure, are essential for the expression of biological activity by these peptides. Both peptides inhibited ADP-induced platelet aggregation. Extended homologies around the RGDS sequences in human von Willebrand Factor and bovine fibrinogen were found with both peptides. PMID- 2191723 TI - Modulation of vincristine sensitivity of human kidney tumor cells by pharmacological agents interfering with intracellular signals. No apparent relationship to changes in cytoplasmic Ca2+ or pH. AB - The effect of substances proposed to modulate intracellular signal systems on growth and sensitivity to vincristine in the human kidney tumor cell line ACHN was investigated and related to changes in cytoplasmic free Ca2+ concentration ([Ca2+]i) and cytoplasmic pH (pHi). Presence during culture of the protein kinase C (PKC) activator 12-O-tetradecanoyl phorbol 13-acetate (TPA) had no effect on cell growth but significantly increased the EC50 concentration for vincristine inhibited cell growth. There was no indication for endogenous PKC activity being responsible for basal vincristine insensitivity since it was not affected by the PKC inhibitor H-7. The Ca2+ ionophore ionomycin tended to increase cell growth and induced vincristine resistance, whereas the calmodulin inhibitor W-7 had opposite effects. Presence during culture of the adenylate cyclase activator forskolin did not affect basal cell growth but dose-dependently made the cells more sensitive to vincristine. The modulators of vincristine sensitivity had no immediate effect on pHi, whereas after 3 days of incubation ionomycin and forskolin tended to increase pHi. Ionomycin and forskolin induced an immediate increase in [Ca2+]i which remained after 3 days only for ionomycin, whereas TPA decreased [Ca2+]i, a change which tended to remain after 3 days of incubation. It is concluded that perturbation of the intracellular signal system may affect both cell growth and cytotoxic drug sensitivity. However, there is no apparent relationship between immediate or late changes in [Ca2+]i and pHi and vincristine sensitivity. PMID- 2191724 TI - Calcium oscillations in electrically non-excitable cells. PMID- 2191725 TI - The ATP-dependent post translational modification of ferredoxin: NADP+ oxidoreductase. AB - Incubation of thylakoids with purified FNR and [32P]ATP led to the incorporation of phosphate into the FNR. In the absence of added FNR, 32P-labelled FNR could be detected associated with the thylakoids. An amino-acid analysis showed that in the dark, the FNR could be phosphorylated on a serine residue. In the presence of thylakoids, the FNR contained a threonine phosphate which was associated with a light-dependent reaction. The physiological function of this phosphorylation is not clear. Some modifications in NADP(+)-dependent photosystem I (PSI) activity and FNR-membrane association have been observed on the addition of ATP. Whether these changes are linked to the phosphorylation of the FNR remain to be fully elucidated. PMID- 2191727 TI - [Studies on the fauna and ecology of Siphonaptera in the Mongolian People's Republic]. PMID- 2191726 TI - [Separation and comparative characteristics of subunits of phenylalanyl-tRNA synthetase from Escherichia coli MRE-600 and Thermus thermophilus HB8]. AB - Separation of alpha- and beta-subunits of phenylalanyl-tRNA-synthetases from E. coli MRE-600 and Thermus thermophilus HB8 using FPLC has been carried out for the first time. The separated subunits of both enzymes do not possess any detectable tRNA-amino-acylation activity. It was found that in the case of the E. coli enzyme beta-subunits exist in solution mainly in the monomeric form with negligible formation of beta 2-dimers, while alpha-subunits predominantly form alpha 2-dimers over the same concentration range. In the case of Thermus thermophilus phenylalanyl-tRNA-synthetase, both alpha- and beta-subunits mainly exist in the dimeric form. The putative mechanisms of alpha-subunit aggregation and of subunit association for alpha 2 beta 2-type enzymes are discussed. PMID- 2191729 TI - [A diagnostic expert system]. AB - The introduction of new technologies in the field of electronics has influenced the development of technical equipment over the last few years. The progressive miniaturization of integrated circuits makes possible an expansion of the spectrum of functions offered by this equipment. This also applies to medical technology. These more complex units call for new methods of fault detection and diagnosis. In addition to analytical redundancy, tools developed by the artificial intelligence research community, such as expert systems, are becoming more and more important for fault diagnosis. On the basis of a realized diagnosis expert system the possibilities as well as the limits of such system are discussed. Also, possible future developments of artificial intelligence, like machine learning, are considered. PMID- 2191728 TI - Skin conductance habituation in panic disorder patients. AB - Skin conductance habituation was compared between 38 patients meeting DSM-III criteria for Panic Disorder and 29 normal controls. Approximately half of each group was randomly assigned to be given 100 dB SPL tones and the other half 75 dB tones. All indices pointed to slowed habituation in patients compared with normals: number of trials to response habituation, total number of responses, and slope of decline of skin conductance level. Patient-normal differences were not significantly larger for 100 dB than for 75 dB. In addition, patients compared with normals had more nonspecific fluctuations, higher skin conductance levels, and a shorter response latency to the first stimulus. Stepwise discriminant analyses classified patients and normals better in the 100 dB than in the 75 dB condition, and showed that the various skin conductancy variables were largely redundant at the higher intensity. PMID- 2191731 TI - Alcoholism and drug abuse--some legal issues for employers. AB - Three specific areas of the law concern employers faced with problems of addiction at the workplace. At common law an employer may be guilty of negligence where a person has suffered personal injuries or economic loss as a result of an act of negligence committed in the course of employment by an employee. An example would be an employee with a serious addiction to alcohol or drugs who caused an accident in the company car whilst on company business. Employers may also be guilty of a criminal offence for breach of a statutory duty. One such duty is to have a 'safe system of work'. Other statutory rights guarantee employees a right not to be unfairly dismissed and this includes employees with addiction problems. Lastly, employers must be careful not to break the contract of employment if, for example, an employee with an addiction problem were to be suspended from duty or have his company car withdrawn, even if this was a temporary measure only. PMID- 2191730 TI - [c-myc and c-Ha-ras proto-oncogenes in cervical cancer: prognostic value]. AB - The biological behaviour of invasive carcinoma of the uterine cervix is not always predictable. It is therefore important to establish new biological markers which could be useful in determining a more reliable prognosis. We have analyzed the c-Ha-ras and c-myc proto-oncogenes in a large series (154 cases) of cervical cancers at various clinical stages. Alterations of c-Ha-ras (deletion, mutation) and c-myc (amplification) were frequently observed in cervical cancers and were shown to be associated with tumor progression. Furthermore, c-myc overexpression, when detected in early cervical cancers, provides a means of identifying patients at high risk of early recurrence. PMID- 2191732 TI - Changes in the control of alcohol misuse. AB - This paper examines use of the concept of control by policy makers, researchers, health promoters, crime preventers and therapists. It also looks at recently advocated local, 'non-control' measures which are part of the public health arsenal of prevention measures. It is argued that the broadening concerns of the public health perspective may be viewed as a part of the growth of new, more pervasive forms of social regulation and control which should be a concern for those working to reduce alcohol misuse. PMID- 2191733 TI - Coronary artery bypass surgery. PMID- 2191735 TI - Exchange transfusion for severe falciparum malaria in pregnancy. PMID- 2191734 TI - Providing the fetus with calcium. PMID- 2191736 TI - Experiences of a battalion medical officer in the retreat to Dunkirk: II. PMID- 2191737 TI - Depression in childhood. 1. Drugs may be useful. PMID- 2191738 TI - Depression in childhood. 2. A psychoanalytic approach. PMID- 2191739 TI - ABC of major trauma. Initial assessment and management--I: Primary survey. PMID- 2191740 TI - The dangers of a long urological waiting list. AB - Statistics on urological waiting lists suggest that there is considerable regional variation in delay before treatment. This clearly depends on many factors but is unlikely to indicate significant variation in morbidity either at presentation or during subsequent admission for surgery. Managers and politicians should be extremely wary if encouraged to base major changes in distribution of funding and equipment on a casual examination of waiting list figures. It is doubtful if delay in diagnosis or treatment seriously influences morbidity and mortality from urological illness. PMID- 2191741 TI - Radical nerve-sparing prostatectomy with epidural anaesthesia in 100 patients. AB - From August 1985 to January 1989, 100 patients were treated with radical nerve sparing prostatectomy with epidural anaesthesia. Transrectal ultrasound evaluation was available for most of these patients. Using the anatomical techniques of early dorsal vein ligation, hypogastric artery control and epidural anaesthesia, blood loss was minimised and 55 patients required no transfusions. In addition, with the use of ultrasound, PSA determination and pelvic CAT scan, 73 of these 100 patients had organ-confined disease; 66 patients were potent pre operatively and 42 are potent post-operatively. PMID- 2191742 TI - Transitional cell carcinoma of the urachus. PMID- 2191743 TI - Upward migration of a J-shaped internal ureteric stent. PMID- 2191744 TI - Cytoreductive surgery for ovarian carcinoma. PMID- 2191745 TI - Aetiology of venous ulceration. PMID- 2191746 TI - Acute management of spinal cord injury. PMID- 2191747 TI - Gut barrier function and the surgeon. AB - There is accumulating evidence that multiple organ failure is not always the result of an established septic focus. Increasing attention has centred on the gut as a reservoir of bacteria (and bacterial endotoxins) that can traverse the intestinal mucosal barrier (a process called 'bacterial translocation') and initiate the septic state. Although the link between haemorrhagic shock and sepsis was recognized decades ago, the full experimental demonstration of this phenomenon is more recent. It was shown to occur in three main settings: physical disruption of the gut mucosa, impaired defence mechanisms and altered gut microbial ecology. Conditions such as haemorrhagic shock, burns, protein malnutrition and sepsis are seen in the severely ill surgical patient or the multiply injured, and are known to cause various combinations of circumstances favourable to bacterial translocation and endotoxin absorption. These may play an important role in the mortality of the critically ill. PMID- 2191748 TI - Male homosexuality, HIV infection and colorectal surgery. AB - The sexual practices of male homosexuals may lead to the development of a wide variety of colorectal and perianal diseases. This review describes the pathogenesis of these conditions, their management, and the influence of HIV infection on these conditions. PMID- 2191749 TI - Comparison of one dose versus three doses of prophylactic antibiotics, and the influence of blood transfusion, on infectious complications in acute and elective colorectal surgery. AB - In a randomized prospective controlled trial involving 311 patients undergoing acute or elective colorectal surgery, the efficacy and safety of two different single dose and one triple dose regimen of antibiotic prophylaxis, as well as the influence of blood transfusion on postoperative infectious complications, were studied. Postoperative infectious complications occurred in a total of 59 patients (19.0 per cent). There were no major differences between the three treatment groups. Thirty-four patients (10.9 per cent) developed abdominal wound infection, 17 patients (5.5 per cent) intra-abdominal abscess and 16 patients (5.1 per cent) anastomotic leakage. Of 202 patients (65.0 per cent) requiring blood transfusion during hospitalization 57 (28.2 per cent; 95 per cent confidence limits of 23-36 per cent) developed infectious complications, whereas two non-transfused patients (1.8 per cent; 95 per cent confidence limits of 0.2 to 6 per cent; P less than 0.001) developed infectious complications. It is concluded that one single dose of antibiotic prophylaxis in acute and elective colorectal surgery is as protective as a triple dose regimen. The development of infectious complications despite antibiotic prophylaxis is strongly related to blood transfusion. PMID- 2191750 TI - New technique for temporary purse string suture in stapler anastomosis. PMID- 2191751 TI - Whole gut irrigation and Prepacol laxative preparation for colonoscopy: a comparison. AB - Two techniques for preparation of the colon for colonoscopy were compared in a controlled trial. Fifty patients given a low residue diet and the laxative Prepacol were compared with 50 patients given whole gut irrigation. Significantly more patients suffered from vomiting (P = 0.0005), shivering (P = 0.0062) and nausea (P = 0.031) following irrigation; in two cases the procedure had to be abandoned because of profuse vomiting. Irrigation was less well tolerated by the patients (P = 0.00002) than preparation with Prepacol. On the other hand, the quality of bowel preparation was found to be better (P = 0.0005) after irrigation. On two occasions colonoscopy was not possible following Prepacol preparation because of faecal residue. Patients with a previous colorectal resection showed a similar quality of cleansing to those patients prepared with irrigation. We conclude that Prepacol is as efficient as irrigation for patients who have had a previous colorectal resection because the quality of bowel preparation is as good and the associated patient discomfort is small. PMID- 2191752 TI - Vacuum drainage of groin wounds after vascular surgery: a controlled trial. AB - A pilot study of 100 consecutive groin wounds after vascular surgery demonstrated lymph leaks in 12 per cent. Lymph leak was significantly associated with wound infection and with prolongation of in-patient stay. A controlled trial was therefore instituted to assess the influence of vacuum drainage in groin wound healing. One hundred and twenty-seven wounds were randomized to drainage (n = 65) or no drainage (n = 62) and the wounds were examined 'blind' by independent observers. No difference in the incidence of lymph leakage or wound infection was noted between the two groups. The routine use of suction drainage for groin wounds in vascular surgery is unnecessary. PMID- 2191753 TI - Clinical trial of calcium alginate haemostatic swabs. AB - The influence of a new haemostatic material on surgical bleeding was evaluated in 100 patients who were prospectively randomized to either normal surgical gauze or calcium alginate swabs used throughout cholecystectomy (n = 40), simple mastectomy (n = 18) or inguinal hernia repair (n = 42). Overall, median (range) blood loss was 91 (3-329) ml for gauze and was significantly reduced by calcium alginate swabs to 72 (2-181) ml (P less than 0.05). Unexpectedly, operation times were also shortened from 45 (17-95) min for gauze to 35 (13-70) min with calcium alginate swabs (P less than 0.02). This reduction in blood loss and operating time was greatest for mastectomy, was still statistically significant for cholecystectomy, but was unimportant in inguinal hernia repair. Calcium alginate haemostatic swabs may become routine in major surgery, particularly where blood loss leads to the need for transfusion. PMID- 2191754 TI - Comparative analysis of vasotocin-like immunoreactivity in the brain of the turtle Pseudemys scripta elegans and the snake Python regius. AB - The distribution of vasotocin in the brains of the turtle Pseudemys scripta elegans and the snake Python regius was studied with immunohistochemical methods. In both species, vasotocin-immunoreactive (VTi) cells were found in the supraoptic nucleus, the paraventricular nucleus and the bed nucleus of the stria terminalis. No VTi cell bodies were seen in the brainstem. Vasotocinergic fibers were found in all major brain divisions. Intrahypothalamic VTi fibers were observed between the supraoptic and the paraventricular nuclei and in the median eminence. An extensive network of extrahypothalamic VTi fibers extends from the olfactory bulb to the spinal cord. Limbic structures, such as the nucleus accumbens, the septal area and the ventral amygdaloid nucleus, contain a moderate to dense VTi plexus. Other areas with a substantial number of VTi fibers are the lateral habenular nucleus, the ventral tegmental area, the substantia nigra, the locus coeruleus and the nucleus of the solitary tract. Sex-related differences in the density of the VTi fibers were observed in the lateral septal nucleus, the mid-brain periaqueductal gray and, to a lesser extent, in the ventral amygdaloid nucleus, the lateral habenular nucleus, the ventral tegmental area and the substantia nigra. In these areas, the density of VTi fibers is higher in males than in females. The distribution of vasotocin-like immunoreactivity in the brains of Pseudemys and Python resembles the pattern previously observed in the lizard Gekko gecko. However, among the three species several differences exist, the most remarkable one being the variation in number of liquor-contacting VTi cells in the paraventricular nucleus. PMID- 2191755 TI - Gordon memorial lecture. Vaccines and vaccination--past, present and future. AB - 1. Immunisation was first practised as early as the 10th century when small doses of smallpox material administered by unusual routes were used to immunise against smallpox. The procedure was introduced into England in the early part of the 18th century. 2. The next major development was the use by Jenner of cowpox to vaccinate against smallpox in the late 18th century. 3. Some eighty years later came the classic studies of Pasteur developing vaccines for fowl cholera, anthrax and rabies. 4. The studies of Jenner and Pasteur established the major principles of vaccination which are in use to this day. 5. The major viral diseases of the domestic fowl were recognised during the 1920s and 1930s and in most cases vaccines were developed within 5 years of the discovery of the viral nature of the cause of each disease. 6. The desirable properties of poultry vaccines required by the user and producer are not completely fulfilled by currently available vaccines. 7. There is a need to use the opportunities provided by modern biotechnology and immunology to search for and develop vaccines that better fulfil the desirable properties of poultry vaccines. 8. There are a number of strategies available for the development of novel vaccines, some of which are appropriate for the needs of poultry vaccines. PMID- 2191756 TI - Giant-cell tumor of the sphenoid bone: case report and review of the literature. AB - We report the case of a 23-year-old man with a giant-cell tumor of the sphenoid bone. The radiologic manifestations consisted of an expansile mass arising from the sphenoid bone with extension into the cranial cavity and the nasopharynx. The findings with computed tomography and magnetic resonance imaging best reflected respectively the osseous and soft-tissue extent of the disease. PMID- 2191757 TI - Degradation of stored ultrasonographic images. PMID- 2191758 TI - The ocular manifestations of sexually transmitted diseases. AB - The problem of ocular involvement in sexually transmitted diseases is encountered by ophthalmologists in everyday practice. This paper reviews the ocular manifestations of some of the more common sexually transmitted diseases including AIDS, syphilis, gonorrhea and infections caused by herpes simplex, Chlamydia trachomatis and Phthirus pubis. Current methods of diagnosis and treatment are discussed. Neonatal infections associated with sexually transmitted diseases are also reviewed. PMID- 2191759 TI - Corneal changes in Tay-Sachs disease. AB - Tay-Sachs disease is a well-known inherited disease leading to an accumulation of gangliosides in the brain and retina. Our report is based on a case of Tay-Sachs disease in a non-Jewish infant where pathologic changes were noted in corneal endothelium as well as in the retina. PMID- 2191760 TI - Bacteroides fragilis endophthalmitis: a case report. AB - Bacteroides fragilis is an infrequent anaerobic ocular pathogen. Nevertheless, this organism is of particular significance because it may be resistant to many antibiotics that are typically effective against anaerobes. We present what is to the best of our knowledge the first reported case of B. fragilis endophthalmitis. The endophthalmitis presented in a 95-year-old man following extracapsular cataract extraction with posterior chamber intraocular lens implantation. PMID- 2191761 TI - An unusual case of orbital cellulitis. AB - Munchausen's syndrome, an unusual disorder related to malingering and hysteria, is occasionally seen by the ophthalmologist. Munchausen patients deliberately deceive and attempt to manipulate physicians 'through factitious signs and symptoms. They know they are acting, yet appear unable to control their actions. Unnecessary medical workups and inappropriate surgical interventions are common with this perplexing syndrome. An unusual case of orbital cellulitis that illustrates a number of these features is illustrated and the syndrome is reviewed. PMID- 2191762 TI - In situ adenocarcinoma ex pleomorphic adenoma of the lacrimal gland. AB - We report a unique case of in situ adenocarcinoma ex pleomorphic adenoma of the lacrimal gland. The patient is alive and disease-free 2 1/2 years after complete local excision of the tumour. The current clinicopathologic status of this unusual tumour is discussed in the context of the reported experience to date. PMID- 2191763 TI - Preoperative short-term radiation therapy in operable rectal carcinoma. A prospective randomized trial. Stockholm Rectal Cancer Study Group. AB - From 1980 to 1987, 849 patients with clinically resectable rectal adenocarcinoma were randomized into a controlled clinical trial of radiation therapy (2500 cGy over 5 to 7 days) before surgery versus surgery alone. At a median follow-up time of 53 months (range, 8 to 90) the incidence of pelvic recurrence among 679 curatively operated upon patients was significantly lower among those allocated to radiation therapy (P less than 0.01). A reduction was observed in all Dukes' stages. No significant difference between the treatment groups was observed with regard to frequency of distant metastases or overall survival. Among all randomized patients as well as the radically operated patients the recurrence free interval, i.e., time to local recurrence or distant metastasis, was significantly prolonged in the preoperatively irradiated group. The radically operated patients also had a significantly prolonged survival related to rectal cancer (P = 0.05). The postoperative morbidity, however, was significantly higher among irradiated patients. The postoperative mortality was 8% in the radiation therapy group compared to 2% in the surgery alone group (P less than 0.01). PMID- 2191764 TI - Randomized trial of adjuvant tamoxifen combined with postoperative radiation therapy or adjuvant chemotherapy in postmenopausal breast cancer. AB - From 1976 to 1984, 427 postmenopausal women with high-risk breast cancer (pN + or pT greater than 30 mm) were randomized between postoperative radiation therapy (RT), radiation therapy plus tamoxifen (RT-TAM), adjuvant chemotherapy (CT), or chemotherapy plus tamoxifen (CT-TAM). Surgery was a modified radical mastectomy in all cases. The radiation therapy was given with high-voltage techniques and included the chest wall and regional nodes. The dose was 4600 cGy/4 1/2 weeks. Tamoxifen was given at a dose of 40 mg daily for 2 years. The adjuvant chemotherapy consisted of 12 cycles of cyclophosphamide, methotrexate, and 5 fluorouracil (CMF) (or chlorambucil, methotrexate, and 5-fluorouracil [LMF] for patients entered before 1978). At a median follow-up time of 6 1/2 years the recurrence-free survival was significantly better for patients allocated to radiation therapy compared to chemotherapy and for patients allocated to tamoxifen compared to no adjuvant endocrine treatment (P less than 0.01). At 10 years the recurrence-free survival for patients in the RT-TAM, RT, CT-TAM, and CT groups was 63%, 57%, 47%, and 31%, respectively. A significant reduction of treatment failures with tamoxifen was only observed among patients with estrogen receptor-positive tumors. The overall survival difference in favor of patients allocated to radiation therapy or tamoxifen was not significant: the respective survival percentage at 10 years in the RT-TAM, RT, CT-TAM, and CT group was 65%, 62%, 52%, and 50%. The results indicate that postoperative radiation therapy continues to play an important role in the primary management of postmenopausal women with high-risk breast cancer and that the addition of tamoxifen may further improve the results among ER-positive patients. PMID- 2191765 TI - Consumption of methylxanthine-containing beverages and risk of pancreatic cancer. AB - This paper reviews published studies of a possible relationship of consumption of methylxanthine-containing beverages, primarily coffee, to risk of pancreatic cancer (PC). Certain ecologic studies suggested a possible relation of pancreatic cancer mortality and coffee consumption by country. The findings from case control studies are not entirely consistent; in general, no significant increased risk with a clear dose-response relationship is reported, but some of the studies suggest the possibility of some increase in risk. The prospective studies reported generally agree that there is no significant association of coffee consumption with increased risk of PC. The few data available on tea consumption do not suggest an increased risk of PC. It seems reasonable to conclude that current epidemiologic evidence does not suggest any significant increased risk of PC with coffee consumption. Further research might clarify whether the divergent results reported for coffee consumption might be a result of confounding or other methodologic problems or might reflect some small but real increase in risk of PC associated with coffee consumption. PMID- 2191767 TI - Comparison of the fibronectin-binding ability and antitumor efficacy of various mycobacteria. AB - Although the mechanism by which Bacillus Calmette-Guerin (BCG) exerts an antitumor effect on superficial bladder tumors is not fully understood, recent evidence has implicated binding of BCG organisms to fibronectin (FN) as requisite for this antitumor efficacy. Various substrains of BCG and other mycobacteria were tested in vitro for their relative capacities to bind both matrix and soluble FN. A substrain of Mycobacterium kansasii, designated the "high-binding strain," was found to bind FN more readily (P less than 0.05) in in vitro studies, when compared to commercially available substrains of BCG (Tice, Connaught, and Armand Frappier). The binding by the three commercial strains of BCG to FN in vitro appeared to be equivalent. The high-binding strain was further demonstrated to attach more readily in vivo to the acutely injured murine bladder (P less than 0.005) than the Armand Frappier substrain. Finally, using the MB49 murine bladder tumor model, an enhanced antitumor effect (P less than 0.05) was noted in mice treated with intravesical high-binding strain, in comparison to the Armand Frappier substrain, during five weekly treatments. It appears not only that the commercial substrains of BCG bind FN in an equivalent manner but also that the relative binding capacities of the substrains correlate directly with antitumor activity. A substrain of M. kansasii appears to have been identified which may prove more clinically effective than the currently available strains of BCG. PMID- 2191766 TI - Molecular cytogenetics: Rosetta stone for understanding cancer--twenty-ninth G. H. A. Clowes memorial award lecture. PMID- 2191768 TI - Phase I and clinical pharmacological evaluation of pirozantrone hydrochloride (oxantrazole). AB - Pirozantrone hydrochloride, an anthrapyrazole analogue, was selected for clinical evaluation based on broad antitumor activity against murine tumor systems and on potentially less cardiotoxicity when compared to anthracyclines. This anthrapyrazole analogue is currently under clinical evaluation, and we now report results on a Phase I clinical trial incorporating a pharmacologically guided dose escalation scheme. Dose escalation was designed to proceed by factors of 2 until the patient drug exposure (concentration x time) was 40% of the murine exposure at the LD10 dose (90 mg/m2). Thereafter, more moderate dose escalations were employed. The target concentration x time value (59 micrograms-min/ml) derived from preclinical pharmacology data was exceeded in all three patients at a dose of 90 mg/m2. A dose of 160 mg/m2 was found to reproducibly result in appropriate myelosuppression. This dose is recommended for further testing in Phase II studies. Nonhematological toxicities encountered in this trial were mild, the most notable being phlebitis at the infusion site. Objective responses were observed in two patients, one with metastatic breast cancer and another with metastatic melanoma. Following a 60-min infusion, pirozantrone hydrochloride plasma elimination was monoexponential, with a half-life of approximately 30 min, mean total body clearance of 1.29 liters/min/m2, and mean steady state volume of distribution of 29 liters/m2. PMID- 2191769 TI - Serum carcinoembryonic antigen level increases correlate with tumor progression in patients with differentiated gastric carcinoma following noncurative resection. AB - Serum carcinoembryonic antigen (CEA) levels were determined serially in 30 preoperative and postoperative patients with differentiated and 47 with undifferentiated gastric cancers. Macroscopic noncurative resection of the stomach was done for those patients. There was no difference between survival curves in the differentiated and undifferentiated cases, and the 50% survival was 13.1 months for the differentiated group and 12.5 months for the undifferentiated group. Preoperative serum CEA levels were 10.4 +/- 5.2 ng/ml for the differentiated and 4.0 +/- 1.6 ng/ml for the undifferentiated cases, and CEA positive rates were 20.0% for the differentiated and 14.9% for the undifferentiated cases. There was no difference in preoperative CEA values with regard to tissue types. In the course of tumor progression, CEA levels increased during the first postoperative year in the differentiated cases and related reciprocally to decreases in survival rates. Little change was noted in the undifferentiated cases. Therefore, the serial postoperative assay of serum CEA levels has predictability with regard to tumor progression in patients with a differentiated gastric cancer. PMID- 2191770 TI - Mutational analysis of the H-ras oncogene in spontaneous C57BL/6 x C3H/He mouse liver tumors and tumors induced with genotoxic and nongenotoxic hepatocarcinogens. AB - The frequency and mutational profile of H-ras gene activation were determined in spontaneous liver tumors of male C57BL/6 x C3H/He mice and in tumors induced with the genotoxic hepatocarcinogen benzidine.2 HCl or the nongenotoxic hepatocarcinogens phenobarbital, chloroform, and ciprofibrate. DNA sequence analysis of the H-ras gene from representative tumors revealed that 32 of 50 (64%) spontaneous tumors and 13 of 22 (59%) benzidine.2 HCl-induced tumors contained a point mutation in codon 61. Tumors induced with the nongenotoxic agents had a much lower frequency of codon 61 mutations, i.e., phenobarbital, 1 of 15 (7%); chloroform, 5 of 24 (21%), and ciprofibrate, 8 of 39 (21%). No mutations were observed at codons 12, 13, and 117 in tumors from any of the groups. Only three base pair substitutions within codon 61 were found. The one most frequently detected in all of the groups was a C.G to A.T transversion at the first nucleotide position, occurring at a 59%, 85%, 100%, 80%, and 88% frequency in the spontaneous tumors and in the tumors induced with benzidine 2.Hcl, phenobarbital, chloroform, and ciprofibrate, respectively. In these same groups an A.T to G.C transition or an A.T to T.A transversion at the second nucleotide position occurred at a frequency of 34%, 8%, 0%, 0%, and 12%, and 6%, 8%, 0%, 20%, and 0%, respectively. The number of tumors carrying an activated H ras gene in the nongenotoxic treatment groups is within the range that would be expected if those animals had not received any treatment. This indicates that the activation of the H-ras gene in those tumors is probably the result of a spontaneous event. The data suggest that these toxicologically and pharmacologically diverse nongenotoxic hepatocarcinogens increase the frequency of liver tumors but do not induce mutations in the H-ras gene. Instead these agents appear to interact with a population of cells that do not contain an activated H-ras gene. This suggests that the mechanisms of tumor development by these nongenotoxic carcinogens differ at least partially from the mechanisms responsible for the development of spontaneous tumors or those induced by a typical genotoxic agent. PMID- 2191771 TI - Transient alterations in the expression of protease and extracellular matrix genes during metastatic lung colonization by H-ras-transformed 10T1/2 fibroblasts. AB - It has been proposed that tumor progression is a selective process and that only a minority of tumor cells survive this selection because they possess the phenotypic traits necessary for metastasis and organ colonization. Both proteases and extracellular matrix proteins have been implicated in invasion and metastasis formation. To examine the nature of the selection process, we transformed 10T1/2 fibroblasts with T24 H-ras and the neoR gene and selected a clonal line expressing the mutant ras gene. After i.v. injection of this line into syngeneic C3H/HeN mice, tumor cells were recovered from lungs by enzymatic treatment and selective outgrowth in G418. Less than one of 10(3) cells survived in the lung 30 min after inoculation, and these exhibited a unique phenotype. This was characterized by a propensity to lodge in the lung on reinjection; markedly enhanced mRNA levels of procollagen alpha 2(I), procollagen alpha 1(III), and fibronectin; and decreased levels of laminin, major excreted protein (procathepsin L), transin, and H-ras. Between 1 and 9 days after tumor injection, the phenotype of the cells surviving in the lung changed dramatically and exhibited a pattern of gene expression with increased protease and low matrix protein mRNA levels. This coincided with a 26-fold increase in the ability to colonize lungs on i.v. injection. Both the phenotype characterized by its propensity to arrest in the lung and that showing enhanced metastatic ability were unstable on prolonged in vitro culture. We hypothesize that two selection events have occurred. The first is for lung arrest and implantation of variants of the injected tumor with high matrix protein and low protease levels. A second selection then occurs for tumor cells that carry a favorable phenotype for invasion and proliferation which is associated with low matrix protein and high protease gene expression. These two phenotypes are represented within a clonal population of recently transformed tumor cells. PMID- 2191772 TI - Nephrotic syndrome in the first three months of life. AB - When the nephrotic syndrome develops within the first 3 months of life it is considered as congenital. In a review, different types of renal diseases are found behind the syndrome in early infancy. A classification of these is proposed, based on clinicopathology. Five classes with subgroups are described, and the necessity of recognizing these for prognosis, therapy and genetic counselling is emphasized. PMID- 2191773 TI - Diagnosis and management of the hydronephrotic type of multicystic dysplastic kidney. Use of antegrade pyelography. AB - The distinction between the hydronephrotic type of multicystic kidney disease and ureteropelvic junction obstruction can be difficult using conventional imaging techniques. Antegrade pyelography with or without percutaneous nephrostomy may be performed to confirm the diagnosis of complete ureteral obstruction and to guide management decisions. One may elect either immediate nephrectomy or observation after performance of this diagnostic procedure. Reconstruction of nonsalvageable kidneys is avoided. PMID- 2191774 TI - Kinetics and specificity of alginate lyases: Part I, A case study. AB - Purified preparations of alginate lyase from Klebsiella aerogenes and Haliotis sp. were investigated for activity and degradation patterns with alginate and alginate fragments having different compositions and sequences. With fragments approaching homopolymers of guluronate and mannuronate, Michaelis-Menten kinetics were obeyed and kinetic parameters could be obtained. Degradation of alginates containing all four possible linkages in various proportions, followed by isolation of the fragments and identification of the end groups by n.m.r. spectroscopy, indicated that the enzyme preparations can attack more than one type of linkage. The results are discussed with reference to the concept of specificity for enzymes with copolymeric substrates having non-regular distributions of units. PMID- 2191775 TI - Hydrolysis of beta-D-glucopyranosyl fluoride to alpha-D-glucose catalyzed by Aspergillus niger alpha-D-glucosidase. AB - Aspergillus niger alpha-D-glucosidase, crystallized and free of detectable activity for beta-D-glucosides, catalyzes the slow hydrolysis of beta-D glucopyranosyl fluoride to form alpha-D-glucose. Maximal initial rates, V, for the hydrolysis of beta-D-glucosyl fluoride, p-nitrophenyl alpha-D glucopyranoside, and alpha-D-glucopyranosyl fluoride are 0.27, 0.75, and 78.5 mumol.min-1.mg-1, respectively, with corresponding V/K constants of 0.0068, 1.44, and 41.3. Independent lines of evidence make clear that the reaction stems from beta-D-glucosyl fluoride and not from a contaminating trace of alpha-D-glucosyl fluoride, and is catalyzed by the alpha-D-glucosidase and not by an accompanying trace of beta-D-glucosidase or glucoamylase. Maltotriose competitively inhibits the hydrolysis, and beta-D-glucosyl fluoride in turn competitively inhibits the hydrolysis of p-nitrophenyl alpha-D-glucopyranoside, indicating that beta-D glucosyl fluoride is bound at the same site as known substrates for the alpha glucosidase. Present findings provide new evidence that alpha-glucosidases are not restricted to alpha-D-glucosylic substrates or to reactions providing retention of configuration. They strongly support the concept that product configuration in glycosylase-catalyzed reactions is primarily determined by enzyme structures controlling the direction of approach of acceptor molecules to the reaction center rather than by the anomeric configuration of the substrate. PMID- 2191776 TI - A common structure for neutral polymers isolated from the lipopolysaccharides of reference strains for Serratia marcescens serogroups O17 and O19. PMID- 2191778 TI - Goiter, iodine, and cabbage. PMID- 2191777 TI - Cell-wall glucans of Cryptococcus neoformans Cap 67. AB - Purified cell walls derived from Cryptococcus neofromans Cap 67, an acapsular mutant, consisted of 86% Glc and 7.3% GlcNAc. The integrity of the cell walls was disrupted in three successive extractions with 60% 4-methylmorpholine N-oxide (4 MMNO) at 120 degrees. Four 4-MMNO-soluble D-glucopyranans were isolated. Released within 0.5 h was water-insoluble Gi-1, followed by two water-soluble Gs fractions and water-insoluble Gi-2 over 17.5 h. A 4-MMNO-insoluble residue, containing 27% of GlcNAc, was also isolated. Gi-1 and Gi-2 were isolated as precipitates during dialysis of 4-MMNO extracts and were each reduced with NaBH4 to permit their investigation in alkaline solution. Gs-1 and Gs-2 were separated by ion-exchange chromatography of the water-soluble fractions. The structures of the D glucopyranans were determined by 13C-n.m.r. spectroscopy and by g.l.c.-mass spectrometry of their per-O-methylated derivatives. Gi-1 was a (1----3)-alpha-D glucopyranan (97%) with some (1----4)-D-glucosidic linkages (3%) and no chain branching. Gs-1 and Gs-2 were (1----6)-beta-D-glucopyranans branched at O-3 (10 12%) with beta-D-Glcp-(1----3)-beta-D-Glcp side chains. Gs-2 may have approximately 2% more chain branching than Gs-1. Gi-2 was a D-glucopyranan with 80% of its structure like that of Gi-1, and 20% like that of Gs-1 and -2; the water-insolubility of Gi-2 suggests that these structures were covalently linked. Almost identical D-glucopyranans were obtained from aged cultures that had thickened walls (as observed by electron microscopy). PMID- 2191779 TI - A double-blind comparison of transdermal clonidine and oral captopril in essential hypertension. AB - In a double-blind study, patients with mild essential hypertension were randomly assigned to treatment with transdermal clonidine or oral captopril. After a two- to three-week titration period, blood pressure decreased significantly from 146.3/95.4 to 134.7/85.1 mmHg in the 33 clonidine-treated patients and from 143.0/96.1 to 134.8/87.1 mmHg in the 35 captopril-treated patients; the mean daily doses were 0.2 mg (equivalent) of clonidine and 122.9 mg of captopril. After eight weeks of treatment, blood pressures were reduced to 132.9/85.2 mmHg in the clonidine group (n = 22) and 131.2/82.5 mmHg in the captopril group (n = 16). In black patients, blood pressure reductions were greater with clonidine than with captopril. Four patients were withdrawn from treatment because of side effects in the clonidine group and one in the captopril group. No between-group differences were found in the responses to a quality-of-life questionnaire completed before and after treatment. The clonidine patches were worn during 99% of patient-weeks of treatment; captopril was taken as directed during 64% of patient-weeks of treatment. It is concluded that transdermal clonidine is safe and effective and well accepted by hypertensive patients. PMID- 2191780 TI - Ca2+ imaging in single living cells: theoretical and practical issues. AB - The measurement of intracellular calcium ion concentrations [( Ca2+]i) in single living cells using quantitative fluorescence microscopy draws from a diverse set of disciplines, including cellular biology, optical physics, statistics and computer science. Over the last few years, we have devised and built a number of systems for measuring [Ca2+]i with Fura-2, and have applied them in the exploration of a wide range of biological processes controlled by Ca2+. In this report we discuss these systems and their advantages and limitations. We also describe the theoretical and practical problems associated with using Fura-2 to measure [Ca2+]i, and the solutions that we, and others, have developed to overcome them. The approaches described should provide useful guidance for others interested in imaging [Ca2+] distribution in living cells. The factors that limit current methods are discussed, and areas for future development are highlighted. PMID- 2191781 TI - Inhibition of Fura-2 sequestration and secretion with organic anion transport blockers. AB - Fura-2 is widely used to measure the concentration of cytosolic free calcium, but in many cells the dye does not remain localized within the cytoplasmic matrix. In these cells, Fura-2 is sequestered within intracellular organelles, secreted into the extracellular medium, or both. We have found that, in mouse peritoneal macrophages, J774 cells, PC12 cells, and N2A cells, Fura-2 sequestration and secretion are mediated by organic anion transport systems and are blocked by the inhibitors probenecid and sulfinpyrazone. Under appropriate conditions these agents have little affect on calcium transients, and may facilitate the use of Fura-2 in a variety of cell types. PMID- 2191782 TI - Assessment of Fura-2 for measurements of cytosolic free calcium. AB - Fura-2 has become the most popular fluorescent probe with which to monitor dynamic changes in cytosolic free calcium in intact living cells. In this paper, we describe many of the currently recognized limitations to the use of Fura-2 in living cells and certain approaches which can circumvent some of these problems. Many of these problems are cell type specific, and include: (a) incomplete hydrolysis of Fura-2 acetoxymethyl ester bonds by cytosolic esterases, and the potential presence of either esterase resistant methyl ester complexes on the Fura-2/AM molecule or other as yet unidentified contaminants in commercial preparations of Fura-2/AM; (b) sequestration of Fura-2 in non-cytoplasmic compartments (i.e. cytoplasmic organelles); (c) dye loss (either active or passive) from labeled cells; (d) quenching of Fura-2 fluorescence by heavy metals; (e) photobleaching and photochemical formation of fluorescent non-Ca2+ sensitive Fura-2 species; (f) shifts in the absorption and emission spectra, as well as the Kd for Ca2+ of Fura-2 as a function of either polarity, viscosity, ionic strength or temperature of the probe environment; and (g) accurate calibration of the Fura-2 signal inside cells. Solutions to these problems include: (a) labeling of cells with Fura-2 pentapotassium salt (by scrape loading, microinjection or ATP permeabilization) to circumvent the problems of ester hydrolysis; (b) labeling of cells at low temperatures or after a 4 degrees C pre-chill to prevent intracellular organelle sequestration; (c) performance of experiments at lower than physiological temperatures (i.e. 15-33 degrees C) and use of ratio quantitation to remedy inaccuracies caused by dye leakage; (d) addition of N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) to chelate heavy metals; (e) use of low levels of excitation energy and high sensitivity detectors to minimize photobleaching or formation of fluorescent non-Ca2+ sensitive forms of Fura-2; and (f) the use of 340 nm and 365 nm (instead of 340 nm and 380 nm) for ratio imaging, which diminishes the potential contributions of artifacts of polarity, viscosity and ionic strength on calculated calcium concentrations, provides a measure of dye leakage from the cells, rate of Fura-2 photobleaching, and can be used to perform in situ calibration of Fura-2 fluorescence in intact cells; however, use of this wavelength pair diminishes the dynamic range of the ratio and thus makes it more sensitive to noise involved in photon detection. Failure to consider these potential problems may result in erroneous estimates of cytosolic free calcium.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2191783 TI - Hypothesis: warfarin administered simultaneously with heparin infusion will prevent heparin-discontinuance associated coronary thrombosis. AB - Recent studies have evidenced an association between the time of heparin discontinuance and coronary artery reocclusion. Some investigators have concluded that inadequate heparinization was responsible, and further heparin infusion or an increase in dose would have been indicated. However, several investigators (Rao: Thrombosis Research 24:181-186, 1981; Marciniak and Gockerman: Lancet September 17:581-584, 1977; Fisken et al.: Lancet December 10: 1231, 1977; Conard et al.: Thrombosis Research 22:507-511, 1981; Kakkar et al.: Lancet January 12:103-104; Green: Lancet February 16:374, 375; Harborne and Nicolaides: Thrombosis Research 43:657-662, 1986; Bonen et al.: Thrombosis Research 27:123 124, 1982; Blomback et al.: Acta Physiologica Scandinavica 58:306-318, 1963; Holm et al.: Scandinavian Journal of Haematology 35:564-569, 1985; Andersson et al.: Thrombosis Research 34:333-340, 1984) have demonstrated that antithrombin III levels are reduced in patients on intravenous heparin. Both reduced antithrombin III levels and reduced rate of antithrombin inhibition of thrombin at the time of heparin discontinuance may increase the risk of coronary rethrombosis. If this theory is correct, increasing heparin infusion may exacerbate this risk. We propose an investigation that will provide evidence for or against the decreased antithrombin III theory, and in doing so, test an experimental therapy designed to prevent coronary reocclusion upon heparin discontinuance. In a randomized, placebo-controlled double-blinded study, we will determine whether simultaneous administration of warfarin with heparin initiation provides more time to increase antithrombin III levels and prevent coronary reocclusion upon heparin discontinuance, compared to heparin without warfarin therapy. PMID- 2191784 TI - Diagnosis of unexpected atrial septal defect by inspired hydrogen appearance time in adult patients referred for cardiac catheterization. AB - Atrial septal defects may have clinical consequences regardless of their size. We evaluated the incidence of clinically unsuspected atrial septal defects in 4,411 consecutive adult patients referred for cardiac catheterization by the previously validated method of inspired hydrogen appearance time. Oximetry was performed only when an abnormally short inspired hydrogen appearance time was measured. Seventy-five patients (1.7%) were discovered to have a left-to-right shunt by this method. The shunting was at the atrial level in 65 patients. Thirty-five of these patients (0.8% of all catheterizations) were not suspected of having any form of congenital heart disease by history, physical examination, chest X-ray, EKG, or echocardiogram. In 19 cases there was no significant oxygen step-up and the diagnosis would have been missed by oximetry. The atrial septum was explored during open heart surgery in 7 patients. Atrial septal defects were detected and closed in all. Four patients had the finding confirmed by echocardiography after the catheterization. Small atrial septal defects are frequently not detected by clinical evaluation, noninvasive testing, or oximetry and are easily detected by the rapid, safe, and accurate method of inspired hydrogen appearance time. PMID- 2191785 TI - Assessment of the sensitivity of hydrogen inhalation in the detection of left-to right shunting. AB - For the detection of left-to-right intracardiac shunting, the oximetric and standard indocyanine green techniques are relatively insensitive, in that neither can reliably detect a shunt with a ratio of pulmonary to systemic flow (Qp/Qs) less than 1.3 (percentage shunt, 23%). Although the hydrogen inhalation method is said to be much more sensitive in this regard, no previous study has measured its sensitivity. Accordingly, in 15 patients (4 men, 11 women, aged 38 to 67 years) without intracardiac shunting, hydrogen inhalation was performed 1) without and 2) with an artificially created femoral arteriovenous shunt of known size, and cardiac output was measured by thermodilution. For the 15 subjects with cardiac outputs of 3.64 to 8.10 liters/min, shunts of 22 to 248 ml/min were created, so that the shunts ranged from 0.5% to 3.3%. Hydrogen inhalation detected all shunts greater than or equal to 1.3% (Qp/Qs greater than or equal to 1.01). Of the 10 shunts less than 1.3%, it detected 5, with the smallest being 0.7%. Thus, the hydrogen inhalation technique is extremely sensitive in identifying the presence of left-to-right shunting, far more sensitive than the oximetric and standard indocyanine green methods. PMID- 2191786 TI - Localization of Ca2+ important in myocardial contractile control. PMID- 2191787 TI - Do studies of mechanical restitution tell us anything about the mechanism of Ca2+ release in myocardial cells? AB - We present information from the literature which is discordant with the idea that the trigger Ca2+ for Ca2(+)-induced Ca2+ release from the myocardial sarcoplasmic reticulum (SR) is carried by the inward current. In addition, evidence is emerging to show that recovery of contractility with increasing interval after an excitation-contraction-relaxation cycle (mechanical restitution) begins with repolarization of the sarcolemma, not mechanical relaxation (SR Ca2+ uptake). These two phenomena, if confirmed, would be compatible with a sarcolemmal source of trigger Ca2+. PMID- 2191788 TI - The cardiac Na(+)-Ca2+ exchanger: dependence on membrane environment. PMID- 2191789 TI - Is acidosis the clue to the loss of structure and functioning of the sarcolemma? AB - The only way for a tissue or organ to survive ischemia is by reperfusion or restoration of the blood flow. However, if the ischemic period is too long reperfusion leads to a Ca2+ overload of the myocardial cells and thereby to cell death. The question is; what are the key events during ischemia which cause this transition from reversible to irreversible injury. In this article we discuss whether acidosis may play a crucial role by inducing Ca2+ release from the sarcolemma and reorganization of membrane components especially the membrane lipids, i.e. lateral phase separation, resulting in membrane protein clustering and changes in lipid asymmetry. PMID- 2191790 TI - Interaction of phospholipids with Ca2+ ions. On the role of the phospholipid head groups. AB - Neutral phospholipids play an important role in Ca2+ binding to biomembranes, in particular if the membrane carries a net negative surface charge due to charged lipids or proteins. The concentration of Ca2+ ions in the plane of the phospholipid head groups can be enhanced by at least two orders of magnitude compared to bulk solution. Ca2+ binding furthermore changes the orientation of the phospholipid head groups which is accompanied by variations of the local membrane dipole potential of the order of 10(5) V/cm. Such high electric fields could entail conformational changes of membrane-bound proteins and the Ca2(+) induced reorientation of the lipid dipoles could thus play a regulatory role in membrane function. PMID- 2191791 TI - [Biocompatibility of retropupillary intraocular lenses]. AB - The authors give an account on the incidence of two types of reactions in the early postoperative period (within two weeks) after implantation of retropupilar intraocular lenses. In a group of 320 patients they observed them in 51 (16%) incl. 17 diabetics. In the group of diabetic patients the incidence of reactions was twice as frequent. A typical fibrin reaction starting on the third day after operation was recorded in 18 patients (5%), in the remaining 33 patients (11%) there was increased opalescence of the aqueous humour, and exudation of cels and cellular structures to the lens surface was associated with the surgical trauma, in particular in beginner implantologists. The two mentioned types of reactions do not have a substantial influence on the final functional effect. PMID- 2191792 TI - [Senile macular degeneration. Review]. PMID- 2191793 TI - Chemistry and biology of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-labeled lipids: fluorescent probes of biological and model membranes. AB - Lipids that are covalently labeled with the 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) group are widely used as fluorescent analogues of native lipids in model and biological membranes to study a variety of processes. The fluorescent NBD group may be attached either to the polar or the apolar regions of a wide variety of lipid molecules. Synthetic routes for preparing the lipids, and spectroscopic and ionization properties of these probes are reviewed in this report. The orientation of various NBD-labeled lipids in membranes, as indicated by the location of the NBD group, is also discussed. The NBD group is uncharged at neutral pH in membranes, but loops up to the surface if attached to acyl chains of phospholipids. These lipids find applications in a variety of membrane-related studies which include membrane fusion, lipid motion and dynamics, organization of lipids and proteins in membranes, intracellular lipid transfer, and bilayer to hexagonal phase transition in liposomes. Use of NBD-labeled lipids as analogues of natural lipids is critically evaluated. PMID- 2191794 TI - Trisomy 20q. A new case and further phenotypic delineation. AB - The present report concerns the clinical and cytogenetic findings in a liveborn girl with trisomy for the long arm of chromosome 20. She was the unbalanced product of a maternal t(18;20)(q23.2;q13.1) translocation. Our case is compared to the 3 previous reports of trisomy 20q associated with telomeric translocation. Adenosine deaminase dosage falls in the normal range and confirms the exclusion of the ADA locus from the region extending distally to 20q13.1. PMID- 2191795 TI - Metabolism of tetradecapeptide, angiotensinogen and angiotensin I and II by isolated perfused rat hindlimbs. AB - 1. We investigated the mechanism of tetradecapeptide-induced vasoconstriction by studying the metabolism of tetradecapeptide (TDP), angiotensinogen, and angiotensin I (AI) and angiotensin II (AII) by isolated perfused rat hindlimbs. 2. Using HPLC and specific RIAs we have quantified six angiotensin peptides: pentapeptide(4-8), hexapeptide(3-8), heptapeptide(2-8), octapeptide(1-8), nonapeptide(2-10) and decapeptide(1-10) in hindlimb effluent. 3. TDP-induced vasoconstriction was associated with generation of predominantly AI and AII, with smaller amounts of the other peptides measured. 4. Captopril prevented vasoconstriction and inhibited AII production by 80%, indicating a dominant role for AI generation in the vascular response to TDP. 5. Evidence that renin is not the enzyme responsible for AI generation from TDP includes: first, the failure of angiotensinogen to cause vasoconstriction or angiotensin peptide generation despite very high amounts of AI and AII generation from TDP; second, the resistance of the TDP-induced vasoconstriction and angiotensin peptide generation to inhibition by pepstatin; and third, the failure of bilateral nephrectomy 24 h before the experiment to influence the vascular and angiotensin peptide response to TDP. 6. AII was cleared with 41% efficiency, with generation of penta-, hexa-, and heptapeptides. 7. AI was cleared with 59% efficiency; this was reduced to 24% by captopril, indicating a conversion of at least 35% of AI to AII by ACE. 8. These studies have identified vascular metabolism of AI and AII to be an efficient process, with both ACE and aminopeptidases playing an important role, and indicate that those peptidases which cleave TDP to generate AI are unlikely to play any role in AI generation in vivo. PMID- 2191796 TI - Ant, bee, and wasp stings. AB - Stinging insect envenomation and allergy remain important clinical and research problems. Approximately 40 deaths occur annually as a result of these stings. The dermatologist can help to avoid this outcome by appropriate recognition of the offending insect and by instituting or arranging the appropriate therapy and avoidance. Bee-sting kits should be encouraged for sensitive individuals. Dermatologists should be alert to the increasing imported fire ant problem, be able to make the diagnosis, and help the patient recognize and avoid these pesky arthropods. PMID- 2191797 TI - Flies and myiasis. AB - Many species of flies cause insect bites. The Lutzomyia and Phlebotomus flies, which carry leishmaniasis, and the Simulium flies, which carry onchocerciasis, have the greatest impact. Fly larvae, or maggots, can be used to cleanse necrotic debris from a wound. Although repulsive, this may be effective. Some larvae are obligatory parasites of warm-blooded animals and sometimes of man. These must burrow into the flesh in order to develop. Screwworms cause great problems for livestock and, rarely, for man. Dermatobia hominis is the most common such parasite seen in the United States. Infection with this parasite, botfly myiasis, is described in detail. PMID- 2191798 TI - Caterpillar dermatitis. AB - Lepidopterism is the term used to describe the aggregate adverse medical effects resulting from contact with adult or larval forms of butterflies and moths. Histamine, histamine-releasing substances, kinin activators, and other as yet undefined proteins are responsible for cutaneous, cardiovascular, neurologic, and constitutional signs and symptoms of lepidopterism. Insect venom is likely injected into the skin through specialized caterpillar hairs when contact occurs with the insect (or vegetation laden with insect debris). Mild cases of lepidopterism will resolve spontaneously; systemic corticosteroids may aid in the treatment of more serious cases. PMID- 2191799 TI - Mite dermatitis other than scabies. AB - Most mites are small, have mouth parts capable of puncturing, feed on tissue fluids, have a high reproductive rate, and are found in all habitats, including human skin. Mites are important causes of cutaneous diseases and are vectors of important infectious diseases. Mite bites should be considered whenever any unexplained cutaneous eruption is presented to the dermatologist. A knowledge of the biology of the mites that can attack humans is important when taking a history and for identifying the etiology. Treatment of the dermatitis is symptomatic, with a cure depending on the identification and eradication of the causative mite. PMID- 2191800 TI - Spiders and spider bites. AB - The only spiders of real medical importance to humans in the United States are the Loxosceles and Latrodectus species, primarily the brown recluse and the black window, respectively. These spiders bite humans only when trapped or crushed against the skin. Severe brown recluse spider bites produce dermonecrosis within 72-96 hours, which should be treated with rest, ice compresses, antibiotics, dapsone, and surgery delayed for several weeks. Using systemic corticosteroids may be helpful in treating the much rarer systemic loxoscelism, which has minimal skin changes but produces massive hemolysis. Black widow bites do not produce marked skin changes but primarily produce muscle cramping, pain, and other neuromuscular-related symptoms. Though a specific antivenin for black widow bites is available, pain control, muscle relaxants, and calcium gluconate are generally adequate treatment. Many other spiders inflict painful bites, but arachnids do not medically deserve the bad reputation that they generally have with the public. PMID- 2191801 TI - Wells' syndrome, insect bites, and eosinophils. AB - Wells' syndrome is an idiopathic, recurrent, inflammatory dermatosis that appears to result from "dysregulated" tissue eosinophilia. The disease usually remits, and the course is benign despite occasional constitutional symptoms. The histology includes flame figures produced by the deposition of major basic protein on collagen bundles by eosinophils. Flame figures are not unique to Wells' syndrome. The term "eosinophilic cellulitis" is ambiguous, since it has been used for both Wells' syndrome and any eosinophil infiltrate with flame figures. Clinical descriptions suggest that insect bites may precipitate the initial or subsequent episodes of some cases. Insects may also be the vectors for parasitic diseases that should be considered in the differential diagnosis. Drugs and infections, including tinea, may also precipitate episodes. Wells' syndrome may be superimposed on chronic urticaria or may complicate the course of a myeloproliferative disease. The relationship of Wells' syndrome to other idiopathic diseases with eosinophilia is unknown. PMID- 2191802 TI - The skin and the eye. AB - Many systemic diseases may involve the skin and the eye. In some of these disorders, with both prominent ocular and cutaneous manifestations, the clinical findings, pathology, and pathophysiology may be quite similar; in other instances, quite diverse. Most dermatologists are well aware of the cutaneous manifestations of these disorders, but many of us may be unaware of the associated ophthalmologic findings. This article emphasizes and reviews the ocular manifestations of these diseases, hopefully enabling the dermatologist to make timely and appropriate referral to the ophthalmologic consultant. PMID- 2191803 TI - Pregnancy and the skin. AB - Physiologic skin changes and certain dermatoses characteristically occur during pregnancy. Any cutaneous change is rarely ignored, as the patient is concerned about her own and her fetus's well-being. Physiologic changes include pigmentation, vascular growth, varicosities, telogen effluvium, and striae. These changes are reviewed along with other dermatoses usually associated with pregnancy. Some dermatoses of pregnancy are infrequently reported, as an understanding of possible etiologies remains limited for the varied dermatoses. PMID- 2191804 TI - Granulomatous vasculitides and the skin. AB - Wegener's granulomatosis, lymphomatoid granulomatosis, and Churg-Strauss granulomatosis may all have cutaneous involvement. The morphology of cutaneous lesions in these disorders varies from macular erythema to frank gangrenous ulceration. Most often lesions are located on the extremities; however, truncal or facial involvement has been reported, the latter especially in Wegener's granulomatosis. A common histologic finding in these cutaneous lesions is necrotizing vasculitis. However, it is also possible to see Churg-Strauss extravascular granulomas and even periarteritis. Cutaneous involvement with these three forms of systemic granulomatosis generally parallels the systemic course. The treatment for the cutaneous lesions is dictated by the treatment for the systemic vasculitis. It is important to recognize that the cutaneous extravascular granuloma and cutaneous granulomatous vasculitis can be associated with other disorders in addition to systemic granulomatosis. These disorders include most importantly lymphoproliferative diseases, inflammatory disorders such as arthritis, autoimmune diseases, and other inflammatory disorders such as sarcoidosis. Cutaneous involvement with giant cell or temporal arteritis is not common, but ulcerative temporal-parietal scalp lesions are distinctive. Although not common in the United States, Takayasu's arteritis may have several cutaneous manifestations, including erythema nodosum-like lesions. Granulomatous vasculitides have a myriad of cutaneous manifestations. Knowledge of these manifestations may allow for prompt diagnosis in many cases and increased surveillance in other cases for associated systemic illnesses. PMID- 2191805 TI - Livedo reticularis. AB - A wide variety of internal diseases may be associated with livedo reticularis. In adults, the most frequently encountered associated diseases are characterized by vessel wall disease or intravascular obstruction. In the former group, lupus erythematosus is particularly important, since LR along with anticardiolipin antibodies appears to be a marker of serious cerebrovascular and renal disease. Appropriate evaluation of patients presenting with LR includes a careful history and physical examination. Laboratory studies, including a complete blood count, platelets, coagulation profile, cryoproteins, antinuclear antibodies, and anticardiolipin antibodies, are useful screening tools for the important associated diseases. Table 1 summarizes the spectrum of entities associated with LR and points up the challenge of evaluating this distinctive cutaneous finding. PMID- 2191806 TI - Treatment of cutaneous lesions in patients with lupus erythematosus. AB - After proper classification of cutaneous lesions in LE patients and extensive evaluation, we can begin to approach effective therapy. Patients with cutaneous lupus erythematosus (discoid LE or subacute cutaneous LE) generally have a favorable prognosis and can be managed with safe yet effective therapy. Sunscreens are the most important topical therapy. Intralesional corticosteroids are an effective local adjunctive therapy, useful in bringing lesions under control. Systemic therapy with antimalarials, either used singly or in combination, are usually effective. When "standard" therapy fails, azathioprine, retinoids, or occasionally dapsone may be effective. PMID- 2191807 TI - The therapeutic use of topical minoxidil. AB - Topical minoxidil is a trichogenic agent that stimulates the hair follicle via the vasoactive metabolite minoxidil sulfate without any evidence of antiandrogen activity or an effect on the immune system. Less than 5% of the applied dose is absorbed. The therapeutic effect on hair regrowth is demonstrated for androgenetic alopecia in males and females, by a computer-assisted image analysis counting technique of nonvellus hairs from a photographic print. Patients with severe alopecia areata respond poorly to topical minoxidil treatment. The most common adverse reactions are limited to irritant and allergic contact dermatitis on the scalp. The use of retinoic acid with topical minoxidil has been disappointing relative to the increase in systemic exposure. The value of topical minoxidil as an adjunct for the hair transplant procedure and its effect on hair loss from chemotherapy are being evaluated. PMID- 2191808 TI - Abnormalities of glomerular basement membrane in acute postinfectious glomerulonephritis. AB - The segmental abnormalities of glomerular basement membrane (GBM) were studied by electron microscopy in 69 renal biopsies with acute postinfectious glomerulonephritis (APGN) and correlated with the general morphologic features and clinical findings. Thirty-six were children and 33 were adults. Biopsies were grouped into three stages by light microscopy: exudative stage (25 patients), exudative-proliferative stage (26) and proliferative stage (18). Subepithelial deposits or "humps" were present in 59 patients (86%). The frequency of humps was significantly lower at the proliferative stage than that noted in the earlier biopsies (p less than 0.01). Intramembranous, subendothelial and mesangial deposits were shown in 83% to 88% of the patients. The overall frequency of GBM abnormalities was 45%, showing significantly higher frequency in children than in adults (p less than 0.01). Dissolving subepithelial deposits were often present in the foci with GBM abnormalities. The GBM lesions were not related to more severe clinical manifestations or outcomes, but tended to occur more frequently in later biopsies (p less than 0.01). These results suggest that abnormalities of GBM in APGN are more often present than formerly assumed, especially in children, and could be a normal response to subepithelial deposits. The occurrence of these lesions in other types of immune-related glomerulonephritis may be considered along the same lines. PMID- 2191809 TI - Heparin: what is it? How does it work? AB - The anticoagulant agent heparin inhibits thrombosis by interacting with antithrombin III. There are three distinct chemical elements that make up the heparin precursor molecule: Mucopolysaccharides, amino acids, and sugars. Separate from the chemical elements are three unique domains of activity that have been defined based on the functional interaction of heparin with antithrombin III. Bleeding complications are potential side effects of heparin therapy and may be caused by heparin interactions with platelets. However, reducing the size of the molecule (low-molecular weight heparins) and varying the dosage may reduce the risk of excessive bleeding. PMID- 2191810 TI - Warfarin and vitamin K. AB - Warfarin and other 4-hydroxycoumarins are effective antithrombotic agents. They affect four blood coagulation proteins that act sequentially to produce thrombin. Coumarin therapy decreases the biological activity of these proteins, and therefore decreases the rate at which blood clots. As the mechanism by which these drugs act has become clear, it has also been found that vitamin K will overcome the effects of coumarin anticoagulation and can be used to control bleeding side effects of coumarin therapy. Vitamin K is necessary for activity of a liver enzyme, the vitamin K-dependent carboxylase. A second enzyme that recycles an inactive to an active form of the vitamin is inhibited by coumarins. The ability of other liver enzymes to bypass the coumarin-sensitive step greatly enhances the safety of 4-hydroxycoumarins. PMID- 2191811 TI - Deep vein thrombosis: prophylaxis, diagnosis, and treatment--lessons from orthopedic studies. AB - Orthopedic surgery patients are at high risk of developing thromboembolic disease simply by the very nature of the procedures they undergo even if no other risk factor is present. In unprotected total hip replacement patients, the incidence of fatal pulmonary embolism is at least 2% and the incidence of deep vein thrombosis reaches 50%. Noninvasive screening methods for deep vein thrombosis such as cuff impedance phlebography and fibrinogen scanning have been proved accurate in patients with suspected symptomatic deep vein thrombosis. In asymptomatic but high-risk total hip replacement patients, however, these methods have a combined sensitivity of only 23%. Radiological venography still remains the screening method of choice in these patients. Low-dose warfarin prophylaxis reduces the incidence of deep vein thrombosis to 16% and lowers the risk of major bleeding complications tenfold over the traditional higher dose warfarin. It also enhances protection against proximal thrombi compared to dextran, aspirin, or external pneumatic compression. When low-dose warfarin is used for 12 weeks after total hip replacement without routine venography, it drastically reduces fatal pulmonary embolism (no cases in 268 consecutive patients). This prophylactic regimen is also safe in terms of bleeding complications before and after patient discharge. Finally, it is very cost effective: a saving of $176,000 in treating 268 patients compared with routine venography. PMID- 2191812 TI - Venous thromboembolic disease: diagnosis and use of antithrombotic therapy. AB - Several invasive and noninvasive tests are available to aid the clinician in the diagnosis of deep venous thrombosis and pulmonary embolism. Contrast venography remains the standard for diagnosing deep venous thrombosis of the lower extremity, while impedance plethysmography is sensitive, specific, and noninvasive. Compressive duplex ultrasonography is useful for deep venous thrombosis of the thigh down to the popliteal vein. The ventilation-perfusion lung scan is the most common test for diagnosing pulmonary embolism, but pulmonary angiography remains the standard. Heparin is the mainstay of treatment for deep venous thrombosis and pulmonary embolism, with an important role played by warfarin therapy. PMID- 2191813 TI - Transient ischemic attacks and ischemic stroke: indications for anticoagulation. AB - The value of anticoagulant therapy in cerebrovascular disease has not been adequately documented. Until the results of well-designed trials are available, physicians must use these agents on the basis of personal experience, anecdotal reports, and uncontrolled series. We use anticoagulants in selected patients to (1) prevent recurrent cardioembolic stroke, (2) stem the progression of atherothrombotic stroke in progress, and (3) prevent stroke in patients presenting with a series of transient ischemic attacks. Given the improved status of anticoagulants in cerebrovascular disease, it is essential to rule out contraindications or nonthrombotic causes of patient deterioration before they are administered. PMID- 2191814 TI - Blood coagulation and fibrinolysis: an overview. AB - Recent advances in the understanding of blood coagulation provide strong evidence that exposure of tissue factor is the "match" which initiates blood coagulation. A novel plasma protease inhibitor, called EPI or LACI, effectively extinguishes this "match," leaving Factors IXa, VIII, X, V, and II to function as a "fuse." Activated Factors IX, X, and II are controlled by heparin-enhancable protease inhibitors. Activated Factors VIII and V are destroyed by the protein C/S system. Fibrinolysis is largely cell-based and controlled by differential secretion of plasminogen activators and plasminogen activator inhibitors. PMID- 2191815 TI - Variations of airway responsiveness to methacholine and exercise in asthmatic and normal subjects over a 12-month period. AB - This study looked at seasonal fluctuations of airway responsiveness (AR) to methacholine and exercise in ten mild asthmatic and seven normal subjects. Each subject had a monthly methacholine inhalation test. An exercise challenge with measurement of expiratory flows was performed initially in the fall (F), then in winter (W), and in summer (S). Throughout the study, the subjects were asked to record on a diary card twice daily peak flow rates and respiratory symptoms, one week a month. Airway responsiveness to exercise and methacholine remained generally stable throughout the year, although an increase in respiratory symptoms occurred during fall and winter. The overall AR to methacholine was not significantly different during the different seasons (F, W, S and Spring) with the methacholine concentration producing a 20% fall in FEV1, PC20 (mg/ml) values, respectively, of 1.7 +/- 1.2 mg/ml, 1.8 +/- 1.1, 2.1 +/- 1.2, and 2.0 +/- 1.9 for asthmatics and 79.0 +/- 1.2 mg/ml, 66.8 +/- 1.0, 87.3 +/- 1.0, and 73.1 +/- 1.0 for normals. However, short term variations in AR were associated to exposure to antigens and cold weather. Mean daily peak expiratory flows remained generally stable through the seasons. On the three exercise tests, the VO2 max and the mean % fall in FEV1 after maximal exercise showed large variations; these, however, were not significantly different (mean fall: 16.2% (F), 16.6% (W), and 14.7% (S) in asthmatics). In conclusion, although it may increase transiently, overall airway responsiveness to methacholine and exercise remains generally stable in asthmatic and normal subjects throughout the year. PMID- 2191816 TI - Recombinant GM-CSF in patients with poor graft function after bone marrow transplantation. AB - Poor graft function after bone marrow transplantation is an infrequent complication that is fatal for most patients secondary to severe infections or to bleeding. Even a second marrow infusion is usually not successful in restoring hematopoiesis. We treated nine patients with recombinant Escherichia coli derived human granulocyte-macrophage colony-stimulating factor (GM-CSF) for delayed engraftment or graft failure after autologous (n = 6) or allogeneic (n = 3) bone marrow transplantation (BMT). Six patients were given a dose of 10 micrograms/kg/d over 30 min; three patients received lower doses of 3-5 micrograms/kg/d. Seven patients lived longer than 3 days after commencing GM-CSF and could be evaluated for their response. Six of them had a marked rise in neutrophil counts; there was no effect on platelet and reticulocyte counts. Two patients died within the first 3 days after starting GM-CSF, although both seemed to have some response to GM-CSF (increasing blood neutrophils in one, and increasing macrophages in the bone marrow on autopsy in the other). Side effects most likely attributable to GM-CSF administration were mild and included diarrhea and abdominal pain, low grade fever and mild rash. Severity of graft-vs-host disease (GVHD) was not enhanced in the recipients of allogeneic marrow. We conclude that recombinant GM-CSF can be safely given to patients with poor graft function after marrow transplantation. In some patients, this may lead to a subsequently sustained neutrophil recovery. PMID- 2191817 TI - Pulmonary diffusing capacity in adult cystic fibrosis: reduced positional changes are partially reversed by hyperoxia. AB - In seated adult cystic fibrosis (CF) patients, vascular recruitment of the relatively normal regions of the pulmonary circulation could occur in response to vascular destruction or hypoxia elsewhere in the pulmonary vasculature, thus limiting overall reductions in the single breath CO diffusing capacity (DLcoSB) with advancing disease. The purpose of this study was to determine the extent to which pulmonary capillary recruitment limits reductions in DLcoSB in seated adult cystic fibrosis patients, to define the role of hypoxia, and to develop strategies to improve detection of diffusion abnormalities in this disease. In normal subjects and adult CF patients breathing room air, and in a subgroup, after breathing both 40% and 100% O2 for 20 min, we measured changes (compared to sitting) in the three equation DLcoSB by changing transvascular pressure either with 15 degrees head down position (15 degrees HD), or with high negative inspiratory pressure (HNIP). In CF patients breathing room air, the changes in DLcoSB with both 15 degrees HD and HNIP were significantly smaller (p less than 0.01) than in controls and the positional changes correlated with the degree of airway obstruction. Although CF patients had no significant positional changes in diffusional resistance (1/DLcoSB) breathing room air, the positional changes in 1/DLcoSB after breathing 100% O2 for 20 min were similar in magnitude to the positional changes in normal subjects. We conclude that compensatory pulmonary capillary recruitment occurs in the relatively normal regions of the pulmonary vasculature breathing room air in the resting seated position in CF patients, thus minimizing reductions in DLcoSB in the seated position. This accounts for reduced responses of DLcoSB to both position and HNIP. The improved positional changes in 1/DLcoSB breathing hyperoxic gas mixtures in CF patients suggests that the vascular recruitment breathing room air is partly due to hypoxic vasoconstriction rather than due solely to fixed pathological changes in the pulmonary vasculature. PMID- 2191818 TI - Spontaneous urinary extravasation during a diuretic radionuclide renal study. Report of two cases. AB - Spontaneous urinary extravasation has been observed in excretory urography, but this complication has not been reported when a diuretic radionuclide renal study is used. This study reports two cases demonstrating this phenomenon. The lack of documentation of this occurrence may be related to the infrequency of this complication. Urinary extravasation is relatively innocuous although there are potential risks, as there are in excretory urography. The clinical usefulness of this study, however, clearly outweighs these potential risks. PMID- 2191819 TI - Stable isotopes in clinical pharmacokinetic investigations. Advantages and disadvantages. PMID- 2191820 TI - Formation of active metabolites of psychotropic drugs. An updated review of their significance. AB - Most of the currently available psychotropic drugs form 1 or more active metabolites during in vivo biotransformation in humans and/or animals. In some cases these metabolites are rapidly conjugated and excreted, but in others they attain blood and/or brain concentrations within the same range as, or even higher than, those of the parent drug, thus being potential biologically active compounds. The formation of metabolites with their own biological activity in addition to that of the parent compound may result in a complex situation where different chemical species participate in the final effects. These chemical species may have different pharmacokinetic properties of distribution and clearance. They may act by similar mechanisms, by different mechanisms or even antagonistically. The formation of active metabolites may be important not only for the therapeutic outcome but also for explaining the toxicity of particular drugs. The examples given, although limited, provide evidence that studies on drug metabolites are essential for an understanding of the mechanism of action of psychotropic drugs, and for extrapolating pharmacological and toxicological findings from animals to humans. The development of any new psychotropic agent requires knowledge of the pharmacology and toxicology of all active species as well as their pharmacokinetic profile, including the extent to which they reach the central nervous system. PMID- 2191823 TI - [NMR studies of the whole body--results of a multicenter study for evaluating nuclear magnetic resonance tomography]. AB - Within the framework of a national multi-centre study the spectrum of application and the ranking of magnetic resonance tomography were investigated. Although scans of the brain and vertebral column still dominate the scene, it has become evident that whole body scanning via MR can be very accurate for certain indications. This is particularly true for examinations of gynaecological diseases (95%) and for lesions of the liver (97%). However, the number of problems in which MR can provide answers to diseases in the whole body range is still limited, and hence it would be most desirable to achieve further instrumental and methodical improvements. PMID- 2191822 TI - Pharmacokinetic drug interactions with oral contraceptives. AB - Oral contraceptive steroids are used by an estimated 60 to 70 million women world wide. Over the past 20 years there have been both case reports and clinical studies on the topic of drug interactions with these agents. Some of the interactions are of definite therapeutic relevance, whereas others can be discounted as being of no clinical significance. Pharmacological interactions between oral contraceptive steroids and other compounds may be of 2 kinds: (a) drugs may impair the efficacy of oral contraceptive steroids, leading to breakthrough bleeding and pregnancy (in a few cases, the activity of the contraceptive is enhanced); (b) oral contraceptive steroids may interfere with the metabolism of other drugs. A number of anticonvulsants (phenobarbital, phenytoin, carbamazepine) are enzyme-inducing agents and thereby increase the clearance of the oral contraceptive steroids. Valproic acid has no enzyme inducing properties, and thus women on this anticonvulsant can rely on their low dose oral contraceptive steroids for contraceptive protection. Researchers are now beginning to unravel the molecular basis of this interaction, with evidence of specific forms of cytochrome P450 (P450IIC and IIIA gene families) being induced by phenobarbital. Rifampicin, the antituberculous drug, also induces a cytochrome P450 which is a product of the P450IIIA gene subfamily. This isozyme is one of the major forms involved in 2-hydroxylation of ethinylestradiol. Broad spectrum antibiotics have been implicated in causing pill failure; case reports document the interaction, and general practitioners are convinced that it is real. The problem remains that there is still no firm clinical pharmacokinetic evidence which indicates that blood concentrations of oral contraceptive steroids are altered by antibiotics. However, perhaps this should not be a surprise, given that the incidence of the interaction may be very low. It is suggested that an individual at risk will have a low bioavailability of ethinylestradiol, a large enterohepatic recirculation and gut flora particularly susceptible to the antibiotic being used. Two drugs, ascorbic acid (vitamin C) and paracetamol (acetaminophen), give rise to increased blood concentrations of ethinylestradiol due to competition for sulphation. The interactions could have some significance to women on oral contraceptive steroids who regularly take high doses of either drug. Although on theoretical grounds adsorbents (e.g. magnesium trisilicate, aLuminium hydroxide, activated charcoal and kaolin) could be expected to interfere with oral contraceptive efficacy, there is no firm evidence that this is the case. Similarly, there is no evidence that smoking alters the pharmacokinetics of oral contraceptive steroids. These agents are now well documented as being able to alter the pharmacokinetics of other concomitantly administered drugs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2191824 TI - [Obstacles to the routine use of magnetic resonance imaging--results of a multicenter study for evaluating nuclear magnetic resonance tomography]. AB - Within the framework of this study, the factors that impair the value of MR scans were also investigated and analysed. It was found that artifacts occurred in a large number of examinations that exercised a negative effect on the results. Artifacts are particularly seen in the thorax (54%) and upper abdomen (57%), but they have also been reported in 23% of the CNS examinations. The sources of such artifacts were mainly movements in the investigated layer, whereas other causes were negligible. In the 21,633 examined patients no undesirable effects caused by the examination were noted that would have impaired the patient or the course of the study. On an average, 88% of the examinations were performed with normal tolerance of the examination. In the remaining cases there was motor unrest or claustrophobia requiring special measures, thus hampering the course of the examination. PMID- 2191821 TI - Furosemide (frusemide). A pharmacokinetic/pharmacodynamic review (Part II). AB - Part I of this article, which appeared in the previous issue of the Journal, covered the physical properties, pharmacology, toxicology and pharmacokinetics of furosemide (frusemide). In part II the authors examine the pharmacodynamics of the drug, and suggest various areas for future study. PMID- 2191825 TI - [Evaluating magnetic resonance tomography studies of the extremities--results of a multicenter study for evaluating nuclear magnetic resonance tomography]. AB - MR examinations of the extremities occupy the first place in whole body examinations via MR. Highest accuracy quotas in this area with an average of 93.8% were obtained for tumours, trauma and necroses of the bones. These high accuracy quotas, however, were achieved only if sufficient preliminary information was available. Other statistically significant factors were found to be the field strength, the combined use of spin echo and fast imaging sequences and the use of the multislice technique. PMID- 2191826 TI - [Use of digital subtraction arthrography in lesions of the rotator cuff- comparison with ultrasound]. AB - 60 patients with suspected lesion of the rotator cuff were examined by digital subtraction arthrography and the results were compared to ultrasound. The dynamic study of digital subtraction arthrography visualised in 22 of 23 complete or incomplete cuff tears the exact location of the extravasation of the contrast medium. All diagnoses were confirmed by surgery. Problems of conventional arthrography were not seen by the digital method. PMID- 2191827 TI - Pulmonary arteriovenous malformations: the radiologist replaces the surgeon. PMID- 2191828 TI - Thrombolysis--a challenge for radiologists and surgeons. PMID- 2191829 TI - A hypoechoic area within the head of the pancreas--a normal variant. AB - Using conventional pancreatic ultrasonography 32 healthy volunteers were studied to assess the prevalence of a previously undescribed well demarcated hypoechoic area within the head of the pancreas. There was definite evidence of a hypoechoic region in nine subjects (28.1%), possible evidence in five (15.6%) and no evidence in 18 (56.3%). In accordance with the structural differences that have been described between the embryologically derived ventral and dorsal pancreatic segments it is proposed that this area of hypoechogenicity is the ventral portion of the pancreas. To date any focal hypoechogenicity within the head of the pancreas has been considered abnormal, but in view of these findings we feel it is important to recognise that a well demarcated hypoechoic region within the head of the pancreas can be a normal variant. PMID- 2191830 TI - Xanthogranulomatous pyelonephritis in childhood. AB - A case of multifocal xanthogranulomatous pyelonephritis (XPN) in childhood diagnosed by ultrasound, computed tomography and needle biopsy is described. Following antibiotic therapy, ultrasound and a DMSA renal scintiscan showed no discernible scarring and restoration of function. This has not been previously described. PMID- 2191831 TI - Unusual appearance of renal lymphoma. PMID- 2191832 TI - The effect of enrollment in a prepaid health plan on utilization of a community crisis intervention center by chronically mentally ill individuals. AB - When a prepaid Medicaid Demonstration Project was initiated in Hennepin County, Minnesota, concerns were raised that the new system might place an additional service burden on County-funded mental health agencies responding to underprovision of mental health services by prepaid health plans. This study examined the use of a single County mental health services agency, the Crisis Intervention Center, by a group of vulnerable and frequent users, the chronically mentally ill. The study found that use of the Center by persons enrolled in a prepaid plan declined after enrollment and was different and lower for the prepaid group than for a comparison group of fee-for-service system users during the same time periods. The difference did not meet conventional levels of statistical significance. This finding is nonetheless important since it may be an indication of successful case management by prepaid health plans in serving chronically mentally ill individuals. PMID- 2191835 TI - Sex differences in spatial ability and activity in two vole species (Microtus ochrogaster and M. pennsylvanicus). AB - The hypothesis that sex differences in maze learning result from sex differences in activity was tested with wild-caught prairie (Microtus ochrogaster) and meadow (M. pennsylvanicus) voles. For 38 voles error production and activity were simultaneously measured in a series of 7 symmetrical mazes. Repeated-measures analyses of variance (ANOVAS) examined species, sex, maze, and interaction effects for 3 dependent variables: errors, activity, and errors/activity. The pattern of significant effects was very different for the errors and activity ANOVAS, which suggests that differential activity cannot explain differential error rates. In contrast, the pattern of effects was very similar for errors and errors/activity ANOVAS, which suggests that controls for activity do not remove differences in error production. These results fail to support the activity hypothesis. PMID- 2191833 TI - Consumer satisfaction with institutional and community care. AB - Rather than addressing the psychiatric patients' preference between institutional and community care, research has addressed the consumers' satisfaction with the respective milieus. Studies of overall satisfaction have found that at least 50% of patients approve of the overall treatment strategies in both settings. However, the discriminative power of overall analyses is limited. This paper reviews those studies which have evaluated consumer satisfaction with components of treatment across four dimensions; characteristics of staff, treatment services, the physical environment, and activities that foster autonomy. Inpatients are pleased with the quality of staff relationships and the hospital surroundings but find that talk therapy can be a nuisance and do not like the loss of freedom and privacy characteristic of a locked ward. Far less research has been completed on outpatient samples such that the four dimensions cannot be readily applied. Community consumers express similar approval of staff and are less critical of medication interventions than inpatients. Research suggests though, that consumer satisfaction in part reflects patient characteristics. Results of this summary have implications for addressing program development in both institutional and community settings. PMID- 2191834 TI - The prevention of psychopathology in African Americans: an epidemiologic perspective. AB - Although improving the mental health status of African Americans is an important goal, it is not clear that this can be accomplished by increasing access to professional services. Many have argued that stressful social conditions are the major cause of mental disorder in blacks and thus, psychopathology can be prevented by eliminating racism, oppression and poor economic conditions. This review argues that while the notion of primary prevention with African Americans should be taken seriously, there is still a need for more and better epidemiologic research. Three bodies of knowledge relevant to black mental health are addressed: 1) the need for an epidemiologic knowledge base for prevention; 2) coping capacity and vulnerability to stress; 3) risk factor identification. Findings from a national survey of adult African Americans are presented as an example of risk factor identification for the purpose of specifying targets for preventive interventions. The paper concludes that before the prevention of psychopathology in black populations can be achieved, a number of measurement, theoretical and policy issues must be addressed. Specific directions for future research are outlined. PMID- 2191836 TI - Seminoma in renal transplant patients: a patient report and review of the literature. PMID- 2191837 TI - Neurological disorders associated with HTLV-1. PMID- 2191838 TI - An HTLV-I transgenic mouse model: role of the tax gene in pathogenesis in multiple organ systems. PMID- 2191839 TI - Using synthetic peptide reagents to distinguish infections caused by different HIV strains. PMID- 2191840 TI - Human immunodeficiency virus infection of the CNS: characterization of "neurotropic" strains. PMID- 2191841 TI - Group treatment of foster children to reduce separation conflicts associated with placement breakdown. AB - Foster children age seven to 16 participated in a number of group sessions under the leadership of their own caseworkers, directed at the children's feelings about having been separated from their own families. The project revealed important lacks in agency practice with both children and their parents. PMID- 2191842 TI - [A new class of ochre-suppressors in Saccharomyces: mutations in the tRNA-gln gene]. PMID- 2191844 TI - [Clinical signs and diagnosis of hyperkalemia]. PMID- 2191843 TI - [Long-term substitution in homozygous alpha 1-antitrypsin deficiency. Effect of the proteinase-antiproteinase equilibrium in plasma and sputum]. AB - Long-term replacement with human alpha 1-antitrypsin (60 mg/kg once a week intravenously) was carried out in seven patients with homozygous alpha 1 antitrypsin deficiency (7 males, mean age 50.8 [40-59] years) and progressive pulmonary emphysema for an average of 16 (13-20) weeks. After at least 12 weeks' therapy the concentrations of alpha 1-antitrypsin, elastase-alpha 1-antitrypsin complex, alpha 2-macroglobulin, lactoferrin and elastase inhibition capacity in plasma and sputum were assayed, these assays being performed before starting the alpha 1-antitrypsin infusion and at various times during the following week. After the infusion the plasma concentration of alpha 1-antitrypsin rose from a depressed initial level (median 1.22 g/l) to a level approximately five times higher (median after 1 hour: 5.96 g/l, P less than 0.001), and then declined exponentially, though it never fell below the threshold of 35% of normal which is regarded as the protective level. Elastase inhibition capacity displayed similar changes (r = 0.85). The sputum concentration of alpha 1-antitrypsin rose more slowly than the plasma concentration; from the initial level (median 8 mg/l) it reached a maximum about four times higher after 24 hours (median 36 mg/l; P less than 0.02). Elastase inhibition capacity rose from 151 mIU/ml (median) before the alpha 1-antitrypsin infusion to 450 mIU/ml at 24 hours. These findings suggest that alpha 1-antitrypsin replacement will have beneficial effects on proteinase antiproteinase equilibrium. Determination of elastase inhibition capacity in the sputum is suitable for monitoring dosage during replacement therapy. PMID- 2191845 TI - [Escherichia coli in the human intestine: useful, harmful or meaningless?]. PMID- 2191846 TI - ACE inhibitors in the prevention and therapy of diabetic nephropathy. What is their role? PMID- 2191848 TI - Treatment approaches to reflux oesophagitis. AB - The management of oesophageal reflux disease can and should be highly individualised, depending on the severity of the disease. Mild occasional symptoms of heartburn can often be controlled with conservative measures or changes in diet and antacids. For patients with erosive or ulcerative oesophageal disease, it is becoming clear that acid plays a crucial role in injury and that suppression of acid enhances healing. Antipeptic dosages of histamine receptor antagonists achieve good relief of symptoms but may not always heal erosive oesophagitis. Healing rates are improved with the use of new hydrogen-potassium adenosine triphosphatase (ATPase) pump inhibitors which suppress virtually all acid production. The recurrence of disease is common after acid suppression therapy is discontinued, suggesting the need for some form of long term maintenance therapy. Promotility drugs, which improve oesophageal motility, have inconsistent results in clinical trials and have been associated with a higher rate of adverse drug effects in comparison with acid-suppressive therapies. Surgical treatment should still be considered for patients with chronic recurrent disease who do not respond well to pharmacological therapies. PMID- 2191849 TI - Intravenous streptokinase. A reappraisal of its therapeutic use in acute myocardial infarction. AB - Streptokinase, the first of the thrombolytic agents to be used in acute myocardial infarction, has now been administered to many thousands of patients with this condition. Since early intervention and accessibility of care is paramount in these patients, intravenous infusion of streptokinase has largely replaced intracoronary use. Results of major trials (GISSI, ISIS-2 and ISAM) comparing streptokinase with standard treatment in more than 30,000 patients prove convincingly that intravenous streptokinase increases patient survival after myocardial infarction. The largest trial, ISIS-2, demonstrated a 23% reduction in 5-week vascular mortality after streptokinase use. The greatest benefits occur where streptokinase infusion is initiated early after symptom onset, although late benefit has been observed in patients treated up to 24 hours after pain onset. Importantly, mortality is further decreased by combining streptokinase with aspirin, as shown by a 53% reduction in mortality using the combination in the ISIS-2 trial. Mortality has also been reduced in trials investigating the use of the thrombolytic agents rt-PA and anistreplase. Streptokinase and rt-PA produced similar reductions in mortality in the recent GISSI-2 and International t-PA/Streptokinase Mortality trials, findings which may be further clarified by ongoing comparative trials such as ISIS-3. Reperfusion of about 50 to 60% of occluded coronary arteries occurs with intravenous streptokinase, and left ventricular function is improved. Direct comparisons with rt-PA show a superior effect for the newer agent on early reperfusion, but a similar ability to salvage myocardial function. The complexities of the relationship between reperfusion, left ventricular function and mortality constitute an area of considerable clinical interest requiring further study to clearly differentiate between the drugs available to the physician. The most common adverse events observed during intravenous streptokinase infusion are bleeding complications. An incidence of 3.6% for minor bleeding and 0.4% for major haemorrhage (requiring transfusion) is derived from the combined results of the GISSI and ISIS-2 studies. Bleeding does not appear to be more frequent or severe with intravenous streptokinase than with the more fibrin-selective agent, rt-PA. While the risk to benefit ratio of sequential heparin following streptokinase therapy remains equivocal, the adjuvant use of aspirin confers a clinical advantage over streptokinase alone. In conclusion, streptokinase has now been proven to reduce mortality in patients with acute myocardial infarction, with an acceptable risk of bleeding complications. Given the substantial data that have now accumulated with extensive clinical experience, intravenous streptokinase should be considered a first-line agent in suitable patients. PMID- 2191850 TI - Inhaled pentamidine. An overview of its pharmacological properties and a review of its therapeutic use in Pneumocystis carinii pneumonia. AB - Pentamidine is an aromatic diamidine derivative which has become one of the standard therapies for Pneumocystis carinii pneumonia (PCP), particularly in patients with acquired immunodeficiency syndrome (AIDS). However, with parenteral administration of the drug there is a high risk of toxicity. Inhaled pentamidine produces much higher concentrations of drug on the bronchoalveolar surface with minimal systemic absorption. It has been used successfully for the treatment of PCP in AIDS patients, but its most valuable contribution has been as prophylaxis in AIDS patients at high risk of developing PCP. In prospective controlled studies there has been greater than 80% reduction in relapse rate with pentamidine. The reduction in relapse rate among patients who have experienced one previous episode of PCP has been 50 to 100% compared with historical control groups, over a follow-up period averaging about 6 months. Significant systemic adverse effects to inhaled pentamidine are rare. Respiratory effects associated with inhalation are common but usually controllable without treatment discontinuation. The ideal particle size for even distribution of pentamidine throughout the lung is considered to be 1 to 2 microns. Jet nebulisers such as the 'Respirgard II' system produce a mass median aerodynamic diameter (MMAD) of particles in this range. Ultrasonic nebulisers produce larger particles. The implication from this difference is that while ultrasonic nebulisers may have poorer alveolar distribution and the incidence of local side effects (common with all formulations) may be higher, total drug delivery may be more efficient allowing effective PCP prophylaxis with lower dosages (120 mg vs 300 mg monthly). However, there are no data available comparing the efficacies and tolerabilities of the different formulations of inhaled pentamidine. Nevertheless, inhaled pentamidine would seem poised to become routine prophylaxis in patients with AIDS or AIDS-related complex at risk of developing PCP. PMID- 2191847 TI - Antineoplastic drugs in 1990. A review (Part II). PMID- 2191852 TI - Drug treatment of heart failure. AB - The objectives of treatment for patients with chronic heart failure are the prevention of the initial occurrence, the alleviation of signs and symptoms, the delay of the progression of damage to heart muscle and the reduction of the mortality rate. Many drugs are used in severe heart failure. Current controversy is concerned with which drugs to use in patients with mild heart failure or with left ventricular dysfunction. There is a trend towards the earlier introduction of an angiotensin-converting enzyme inhibitor combined with a diuretic. PMID- 2191853 TI - Early intervention in heart failure. AB - Treatment for patients with congestive heart failure is primarily directed at reducing symptoms and improving functional capacity. In patients with moderate to severe heart failure, therapeutic interventions incorporating diuretics, digoxin and selected vasodilators, specifically angiotensin-converting enzyme (ACE) inhibitors, are designed to correct pathophysiological mechanisms such as left ventricular dysfunction, excessive vasoconstriction and renal reabsorption of sodium and water. Physician-investigators are turning their attention to identifying and treating patients early in the course of their disease. Vasodilator therapy in patients with mild symptoms of heart failure may not only improve exercise performance, but also reduce mortality. In addition, recent studies have suggested that ACE inhibitors may prevent progression of disease in patients with asymptomatic left ventricular dysfunction. It is hoped that ongoing research will demonstrate that early identification and treatment of these patients may prevent development of symptoms and improve survival. PMID- 2191854 TI - M-mode echocardiography in patients with severe congestive heart failure. A subgroup analysis in the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). AB - In the CONSENSUS study, M-mode echocardiography was used as an optional examination. All patients were in severe congestive heart failure [New York Heart Association (NYHA) functional class IV], and all patients had radiologically marked increased heart size. Of 253 patients, M-mode echocardiography was done at baseline in 105 patients. M-mode echocardiographic recordings from 70 patients were received, and of these, only 54 patients (77%) had recordings of acceptable quality for evaluation. At follow-up, M-mode echocardiography was done after 6 weeks, 6 months and 12 months. However, because of the high mortality and the premature cessation of the study, only a limited number of patients had M-mode echocardiographic registrations after greater than 6 weeks. All M-mode echocardiographic registrations were analysed by 2 investigators independently. Systolic time interval (STI) decreased from 0.58 to 0.48 (p less than 0.05) in the enalapril group after 6 weeks. In the placebo group, a small increase in STI from 0.54 to 0.56 (not significant) was seen after 6 weeks. The decrease in STI in the enalapril group was secondary to an increase in left ventricular ejection time. No significant change was seen in left ventricular and left atrial diameters at follow-up: this finding can be explained by a type 2 error. These findings indicate an increased STI in the enalapril-treated group, which could explain why enalapril treatment reduced mortality in the CONSENSUS study. PMID- 2191856 TI - Comparison of oral cholecystography (OCG) with real time ultrasonography in the diagnosis of cholelithiasis at the Tikur Anbessa Hospital, Addis Ababa, Ethiopia. AB - A prospective study of the accuracy of real time ultrasonography in the detection of gallstones was undertaken in 180 patients from February 1987 to February 1988. The ultrasound findings were compared with single dose oral cholecystography (OCG), and with the surgical findings where surgery was undertaken. Ultrasonography gave more accurate results than OCG, with an overall accuracy in the surgically proven patients of 97.1%, no false positive findings and a 2.9% false negative rate. OCG gave an accuracy of 80% with no false positive findings and a 20% false negative rate. Ultrasound was particularly valuable where there was non visualisation of the gall bladder at OCG, giving an overall accuracy of 93.3% in such patients. Ultrasonography is a non invasive, simple, safe and economic diagnostic test of high accuracy in the diagnosis of cholelithiasis and of particular benefit in those patients unsuited for OCG. PMID- 2191855 TI - Effect of enalapril on mortality in congestive heart failure. Follow-up survival data from the CONSENSUS trial. AB - The CONSENSUS trial, which compared the effects of enalapril and placebo on survival in severe heart failure, had a limited blinded treatment period. Follow up for 8.5 months from the end of blinded therapy was performed. Enalapril therapy was encouraged in all patients during follow-up. Of the 135 surviving patients, 58 had previously been allocated placebo and 77 had been allocated enalapril. The follow-up mortality rates in those receiving enalapril were 18 (31%) and 16 (21%), respectively. Mortality was markedly lower in patients treated with enalapril than in those not started on the drug (16% vs 61%). The follow-up data strongly support the original CONSENSUS data regarding reduction of mortality in severe heart failure after the addition of enalapril. PMID- 2191857 TI - Oral contraceptives use and liver tumours: a review. AB - Of the nine epidemiologic controlled studies reporting on the relationship between oral contraceptives use and hepatic tumours, three have findings specifically on the association of oral contraceptives use and hepatocellular adenomas. The strength of this association is reported to be dependent more on long-term oral contraceptive use. Three other studies have reported similar relationships of oral contraceptives use with hepatocellular carcinoma, whereas the remaining three other studies have reported no association between oral contraceptives use and hepatocellular carcinoma. There is however, an increased risk of hepatocellular carcinoma as the duration of oral contraceptives use increases. The risk of developing hepatocellular adenomas is higher in oral contraceptives users over 30 years of age than in the younger age groups. These tumours occur more often in oral contraceptive users taking pills with high doses of estrogens and progestogens; while they are not only associated with oral contraceptives containing mestranol, but also those containing ethinylestradiol. PMID- 2191858 TI - Nutrition and cancer: a review. AB - The issue about the aetiology of malignancies on the whole remains mysterious. There have been strong suggestion that, amongst other things, certain forms of cancer may be diet related. This has led to drastic changes in food consumption patterns in some parts of the Western world. The world over, certain types of cancers have been shown to be on the increase and the changing patterns of food consumption have occasionally been blamed. This paper reviews current thoughts in the relationship between cancer and nutrition. PMID- 2191851 TI - Diltiazem. A reappraisal of its pharmacological properties and therapeutic use. AB - Diltiazem is a calcium antagonist effective in the treatment of stable, variant and unstable angina pectoris and mild to moderate systemic hypertension, with a generally favourable adverse effect profile. It is also effective in terminating supraventricular tachycardia and in controlling the ventricular response to atrial fibrillation/flutter. Atrioventricular block, the risk of which may be exacerbated by concomitant beta-adrenoceptor antagonist therapy, occurs rarely as an adverse effect of diltiazem treatment. Diltiazem appears to exert complex cardioprotective effects which have been of benefit after intracoronary administration to patients undergoing coronary angiography and bypass procedures. In addition, long term diltiazem treatment has produced a significant reduction in subsequent cardiac events in patients with non-Q wave myocardial infarction. Thus, diltiazem is an effective and well-tolerated first-line or alternative treatment of patients with ischaemic heart disease, systemic hypertension, and supraventricular arrhythmias, with possible potential in limiting ischaemia induced myocardial damage. PMID- 2191859 TI - Comparison of commercial kits for the detection of antibody to human immunodeficiency virus type 1 (HIV-1) in Nigeria. AB - Four commercial kits for the detection of antibodies to HIV-1 were compared with regard to their sensitivity, specificity and positive predictive value. The Wellcozyme competitive enzyme immunoassay was the least sensitive (62.5%), while Roche EIA, was the most sensitive (100%). All the commercial kits gave false negative results except the Roche EIA system. The Serodia particle agglutination test had the least positive predictive value of 26.9% while Roche EIA had the highest (88.9%). Our results show that commercial HIV-I antibody test kits are not equally sensitive in detecting positive sera. The practice of using Wellcozyme EIA alone for screening blood meant for transfusion should be discouraged because it does not detect all positive sera and might therefore increase the chances of transfusing HIV-I positive blood. The Roche EIA system appears to be the most reliable for screening blood. Test systems which detect HIV-2 should also be used for screening blood meant for transfusion. PMID- 2191860 TI - Surgical operations in eastern Africa: a review with conclusions regarding the need for further research. AB - This review of surgical ouput in eastern Africa and other developing countries, is based mainly on published, and to a small extent, on unpublished sources, such as hospital annual reports. It is noted that poorly standardized classification of surgical operations is a problem in recording and reporting, and that one internationally agreed classification would be useful in comparative studies. Rates of major surgical operations in sub-Saharan Africa are 70-500 per 100,000 population per year with inguinal hernia repair, caesarean section, hydrocele operation and surgical management of injuries as the most common major operations. There are large variations between hospitals. Corresponding figures in high-income industrialized countries are 5,000-9,000. Data on minor surgery at hospitals are scarce, but figures from a few African hospitals are presented. Almost nothing is known about minor surgery performed at health centres and dispensaries or about surgical cases referred to hospital, and population-based rates of minor surgery cannot therefore be calculated. Resources are scarce, but can be more effectively utilized. Further research should include: (a) population based output of major and minor operations in different countries and regions; (b) outcome after a few selected operations, preferably selected in consultation with researchers studying medical care outcome in other countries; (c) availability and use of surgery-related resources such as manpower, equipment and supplies; and (d) assessment of needs for surgery using household health survey methods. PMID- 2191861 TI - Could saponins be a useful treatment for hypercholesterolaemia? PMID- 2191862 TI - Predictive value of computed tomographic determination of the patency rate of aortocoronary venous bypasses in relation to angiographic results. AB - From 1978 to 1988, 300 patients with 616 aortocoronary venous bypasses underwent computed tomography (CT) 3 months after surgery, and angiography 1 day after CT. Both angiographic patency rate and CT patency rate were 75%. The sensitivity of the CT test for the detection of patent bypass grafts was 90 +/- 1.4%, the specificity of the CT test for the detection of occluded bypass grafts 72 +/- 3.6%. The observed predictive value of a patent CT test resulted in angiographically patent bypasses in 91 +/- 1.3%; the observed predictive value of an occluded CT test resulted in angiographically occluded bypasses in 71 +/- 3.6%. The low specificity for detecting occluded grafts is a considerable limitation of the technique. The pre-post-test patency ratio curve shows better predictive values for the CT test when there is a low pre-test likelihood of patency than when this is high. Patients with a high pre-test likelihood of occlusion, but who actually have patent coronary artery bypasses are most likely to benefit from this non-invasive test. PMID- 2191863 TI - Coronary heart disease in high-risk populations: lessons from Finland. PMID- 2191864 TI - Review of norfloxacin in lower urinary tract infections. AB - A review of worldwide clinical trials with norfloxacin in the treatment of uncomplicated urinary tract infections (UTIs), as well as our personal experience with 215 assessable patients, is presented. Almost all patients received 400 mg b.i.d. for 3-15 days. Bacteriological eradication (10(4) CFU/ml of urine or less) was achieved in more than 90% of patients. Short-term therapy (3 days) with norfloxacin proved to be as effective and tolerable as a 10- to 14-day conventional therapeutic schedule in the treatment of lower uncomplicated UTIs. Overall incidence of drug-related adverse experiences was 2.3%. PMID- 2191865 TI - Review of norfloxacin in complicated and recurrent urinary tract infections. AB - In seven studies of complicated and recurrent urinary tract infections, 285 patients were treated with norfloxacin 400 mg b.i.d. for 7-90 days. The majority of the patients were men, and many were elderly. Underlying diseases included nephrolithiasis, pyelonephritis, prostatism, bacterial prostatitis, prostate cancer, retroperitoneal fibrosis, quadriplegia/paraplegia, neurogenic bladder, and urethral stricture. Many of the infections were due to Pseudomonas aeruginosa or other multiply resistant strains. More than 95% of the pretreatment bacterial isolates were susceptible to norfloxacin. The bacteriologic cure rate ranged from 67 to 100%. Of 45 patients with chronic bacterial prostatitis, 40 (89%) were cured. Few failures of treatment were due to the emergence of bacterial resistance. Of 29 recurrent infections, 6 (20%) were caused by resistant bacteria. Both clinical and laboratory adverse reactions were infrequent and minor, and rarely required discontinuation of therapy. Norfloxacin appears to be an effective drug with an excellent safety profile for the treatment of complicated and recurrent UTIs. PMID- 2191866 TI - Review of the efficacy of oral norfloxacin in pyelonephritis and nosocomial urinary tract infection. AB - One hundred thirty-eight patients with pyelonephritis were treated with norfloxacin, 400 mg twice daily. Women accounted for 74% of cases, and Escherichia coli was the predominant pathogen, accounting for 51% of organisms. Tests for antibody-coated bacteria (ACB) were performed in 48% of patients, and 72% (48 of 67) were positive. Forty percent of the patients had temperatures greater than 37.6 degrees C at the time of study entry. Patients who had both fevers and positive ACB tests had cure rates similar to those of afebrile, ACB negative patients. Norfloxacin was also highly effective in the treatment of multiply resistant, nosocomial urinary tract infections (UTIs), in which Pseudomonas aeruginosa and E. coli predominated. It is concluded that, when used appropriately, i.e., in nonbacteremic patients who are able to absorb oral drugs, norfloxacin is a highly effective alternative modality in the therapy of certain UTIs that historically have been treated with parenteral antibiotics. PMID- 2191867 TI - Norfloxacin versus trimethoprim-sulfamethoxazole in the treatment of urinary tract infections. AB - In a controlled, randomized trial of 133 patients with proven urinary tract infections (UTIs), significantly more pathogens were found to be susceptible to norfloxacin than to trimethoprim-sulfamethoxazole (TMP-SMZ) (p less than 0.01). Among patients with pathogens susceptible to both drugs, more of those treated with norfloxacin were cured or improved (p = 0.06). When at least one patient variable, i.e., prior history of therapy, was corrected for, this difference became significant (p = 0.03). Norfloxacin eradicated 11 of 13 infections due to Pseudomonas aeruginosa and 6 of 7 due to enterococci. Five patients treated with norfloxacin and two treated with TMP-SMZ had relapses within 6 weeks. Significantly fewer adverse experiences occurred in patients receiving norfloxacin (p less than 0.01). PMID- 2191868 TI - Safety profile of quinolones. AB - Tolerability data from reports to Federal Drug Authorities, information from drug companies, medical literature, and personal experience are cited. Tolerability data regarding norfloxacin were derived from more than 31,000 patients in a phase IV study; ofloxacin from more than 14,000 patients in a phase IV study; and ciprofloxacin from more than 8,000 patients during phase II and phase III studies. Adverse experiences occurred in 6.8% of patients treated with norfloxacin, 9.1% with ciprofloxacin, and 9.3% with ofloxacin. The most frequent adverse effects involved the gastrointestinal tract. Untoward effects were generally mild and reversible when therapy was discontinued. PMID- 2191869 TI - Silent myocardial ischemia: a special aspect of coronary artery disease. AB - Silent myocardial ischemia is a serious progressive disease which deserves continuous surveillance. It is characterized by painless ST-segment depression based on coronary artery disease. The mechanisms responsible for producing this condition do not differ from stable angina pectoris. The prognostic implications of silent ischemia are not yet completely clarified. However it could be argued that patients die--whether or not angina pectoris is present--because they develop myocardial infarction or ischemic ventricular arrhythmias. Complex ventricular arrhythmias seem to occur not at a higher rate than in patients with angina pectoris. On the other hand there is no doubt about a present arrhythmogenic potential of a silent myocardial ischemia, but there is so far no clinical evidence that the prognostic significance is different to symptomatic myocardial ischemia. In order to reduce or eliminate ischemic episodes intensive combination medical therapy should be used. If symptoms recur or ischemic changes are persistent, consideration should be given to revascularisation. Nevertheless, the optimal way of treating silent ischemia is still to be defined. PMID- 2191870 TI - Toxoplasma gondii: characterization and localization of antigens secreted from tachyzoites. AB - Since we had previously demonstrated the protective role played by Toxoplasma excreted-secreted antigens, the aim of the present work was to produce monoclonal antibodies directed against these antigens in order to determine if their localization in the parasite is compatible with a mechanism of excretion or secretion. Western immunoblotting analysis revealed three monoclonal antibodies (TG17-179, TG17-43, and TG17-113) raised against excreted-secreted antigens of 28.5, 27, and 21 kDa, respectively. The TG17-179 which reacts with antigens isolated by Concanavalin A affinity chromatography is directed against a glycosylated 28.5-kDa component. Colloidal immunogold labeling showed the ultrastructural localization of the 21-, 27-, and 28.5-kDa antigens in the matrix of the dense granules of tachyzoites and associated with the microvilli network of the parasitophorous vacuole, after host cell invasion. These observations suggest the following mechanism of Toxoplasma secretion: secreted antigens are first stored in tachyzoite-dense granules and are then released inside the parasitophorous vacuole. Among the secretory molecules characterized here, the native 27-kDa antigen recognized by TG17-43 is a calcium-binding protein found to be intermixed with the 21- and 28.5-kDa antigens inside the dense granules and hence could play a role in the packaging of secretory products. In addition, the 21- and 28.5-kDa antigens were also located beneath the parasite plasma-lemma. This particular location could reflect a transient step characteristic of T. gondii secretion. PMID- 2191871 TI - Cyclic AMP- and Ca2(+)-dependent protein kinases in Plasmodium falciparum. AB - The cyclic AMP- and Ca2(+)-dependent protein kinase activities of Plasmodium falciparum were partially characterized after purification of parasites from host erythrocytes by N2 cavitation and Percoll gradient centrifugation. Proteins of molecular weights 80, 54, 51, and 31.5 kDa were phosphorylated in a cAMP dependent manner in cytosolic extracts of isolated P. falciparum. Cytosolic extracts also contained cAMP-dependent histone II-A kinase activity with an average Vmax of 131.1 pmol/32P/min/mg protein and a Km for cAMP of 85nM. Upon photoaffinity labeling with [32P]-8-N3-cAMP, a 53-kDa protein was specifically labeled in parasite cytosol. A metabolically labeled protein of the same molecular weight was identified by cAMP-agarose affinity chromatography. The 53 kDa protein cochromatographed with cAMP-dependent histone II-A kinase activity on DEAE-cellulose, suggesting that it is the regulatory subunit of the kinase. Ca2(+)-dependent phosphorylation of proteins of molecular weights 195, 158, 51, 47.5, and 15 kDa was demonstrated in a membrane fraction from parasites free of the erythrocyte membrane. This activity was not stimulated by either calmodulin or phospholipid plus diacylglycerol and was absent from the membranes of uninfected erythrocytes. Of several exogenous substrates tested, none were found to be a substrate for this Ca2(+)-dependent kinase. Both cAMP- and Ca2(+) dependent kinases phosphorylated serine and threonine residues. PMID- 2191872 TI - Cumulative index of articles. 1962-1986. Vols. 1-25. PMID- 2191873 TI - Reconstructive surgery for deep vein valve incompetence in the lower limb. PMID- 2191874 TI - Brachial artery damage following cardiac catheterisation. When to re-explore. AB - Cardiac catheterisation is frequently performed in modern medical practice and the brachial artery is frequently used. The brachial and forearm systolic pressures were measured by Doppler ultrasound at rest and after hand exercise for 60 s in 75 patients undergoing catheterisation. These objective measurements, together with a history of forearm claudication during the one minute of exercise and clinical examination of the radial pulse were repeated again at 1 hour, 1 week and 3 months. Changes in the forearm/brachial pressure index (PI) at rest and a fall in forearm pressure after exercise were compared with the pre catheterisation values. Sixteen per cent of patients suffered claudication of the forearm during the one minute hand exercise immediately after catheterisation. Of those seen at 3 months, 12% had persistent claudication and all had a markedly reduced PI measured following catheterisation. Conversely, at 1 [corrected] hour after catheterisation, the radial pulse was weak or absent in 20% and 33% were abnormal on Doppler studies and not all had symptoms. It emerges that to avoid claudicating forearms at 3 months, re-exploration, one hour after brachial catheterisation is indicated in some cases. We are inclined to base this upon the 16% who had forearm claudication after one minute of exercise and who also had absent or reduced radial [corrected] pulse and abnormal Doppler studies. Conversely to base the need for re-exploration upon a reduction or absence of the radial pulse [corrected] (20%) on Doppler studies (33%) would lead to an unnecessarily high rate of re-exploration just after the procedure. PMID- 2191875 TI - Eight to ten years follow-up after carotid endarterectomy: clinical evaluation and Doppler examination of patients operated on between 1978-1980. AB - Follow-up information was obtained on 185 patients who consecutively underwent carotid endarterectomy eight to ten years previously. Doppler ultrasound examination was performed in 59 patients who were still alive and living within 100 miles of the hospital. Using lifetable analysis, the annual rate of focal strokes was estimated to be 2% and 1.5% on the operated and the contralateral, non-operated carotid artery, respectively. Doppler examination revealed 48% re stenoses, including 14% occlusion and 15% greater than 50% stenosis. However, there was no association between the occurrence of restenosis and the development of symptoms, perhaps with the exception of internal carotid artery occlusion, which is not an accepted indication for carotid endarterectomy. Together with recent data from the literature, these observations challenge the indication for reoperative carotid surgery. PMID- 2191877 TI - A duplex criterion for aorto-iliac stenosis. AB - Duplex scanning is a new non-invasive test, which enables direct evaluation of aorto-iliac stenoses. The usual duplex criterion for an arterial stenosis is local increase in peak systolic velocity. For haemodynamically significant aorto iliac stenoses a threshold value for this increase has not yet been established. In order to define a duplex criterion for significant aorto-iliac disease. The whole segment was scanned to locate areas with high peak systolic velocities which were then compared to the velocities recorded immediately up and downstream. The value of the highest proportional velocity change was used as the criterion for duplex classification of the segment. Duplex results were compared to the outcome of invasive femoral artery pressure measurements combined with reactive hyperaemia (FAP test). For a range of threshold values of the duplex criterion the specificity and sensitivity was calculated using the FAP test as the gold standard (R.O.C. analysis). The combinations of the highest sensitivity and specificity were obtained in the range of 100-200% change in peak systolic velocity as duplex criteria for significant aorto-iliac stenosis. The highest accuracy (88%) was obtained at a 200% change in the peak systolic velocity. PMID- 2191876 TI - Carotid artery surgery. Local versus general anaesthesia as related to sympathetic activity and cardiovascular effects. AB - Arterial plasma catecholamines, blood pressure and heart rate were determined in 75 patients before, during and after carotid endarterectomy. Local anaesthesia given as a cervical block with skin infiltration containing 200 micrograms adrenaline was used in 28 patients (LA-group), general anaesthesia (nitrous oxide, fentanyl, isoflurane) with skin infiltration containing 200 micrograms adrenaline in 32 patients (GAs-group) and general anaesthesia without skin infiltration in 15 patients (GAo-group). In the LA-Group plasma noradrenaline (P NA) levels were significantly higher during anaesthesia and surgery, with an increase from preanaesthesia levels (P less than 0.05). P-NA decreased from a preanaesthesia level in the GAo-group (P less than 0.01) but remained unaltered in the GAs-group. P-NA values in the GAo-group were lower than those of the GAs group (P less than 0.001) following anaesthesia and surgery. Plasma adrenaline (P A) increased in the LA- and the GAs-group and decreased in the GAo-group (P less than 0.001) following anaesthesia and surgery. In the LA-group P-A was similar before the skin incision and clamping but higher after declamping as compared to the GAs-group. Before the skin incision and thereafter P-A was lower in the GAo group as compared to the other groups. There was a positive correlation between plasma catecholamines, on the one hand, and mean blood pressure and heart rate on the other. Two patients in the LA-, eight in the GAs- and seven in the GAo-group showed a hypotensive blood pressure reaction (SBP less than 100 mmHg; LA vs. GAo, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2191878 TI - Antiplatelet therapy following carotid bifurcation endarterectomy. Evaluation of a controlled clinical trial. Prognostic significance of histologic plaque examination on behalf of survival. AB - To determine whether antiplatelet therapy following carotid bifurcation endarterectomy influences postoperative survival and whether signs of progression in the plaques harvested at the time of surgery might be a prognostic indicator, a controlled clinical trial was undertaken. During 1982 to 1985, 66 patients were recruited, operated on (carotid endarterectomy) and assigned, using the method of adaptive randomisation to the therapy group (n = 32) receiving 1.0 g acetylsalicylic acid (ASA) per day, starting day two prior to surgery, or to the control group (n = 34), which remained without antiplatelet medication. The plaques harvested at the time of surgery were processed using standard histopathological methods and examined "blindly" by light microscopy for signs of arterio-sclerotic progression. The final endpoint was patient survival. The last assessment of the participants survival status was done by June 1989. During follow-up, 20 patients died, six in the treatment group and 14 in the untreated group, the difference being statistically significant (P less than 0.013 Breslow, P less than 0.029 Mantel). In 27 instances the histo-pathological examination showed signs of progression. In this subgroup ASA yielded a significant prolongation of patient survival (P less than 0.017 Breslow, P less than 0.048 Mantel). In the remaining patients no signs of cellular infiltration were evident and no influence of ASA on patient survival was demonstrable (P less than 0.503 Breslow, P less than 0.390 Mantel). PMID- 2191879 TI - Doppler waveform analysis in evaluation of occlusive arterial disease in the lower limb: comparison with distal blood pressure measurement and arteriography. AB - Three Doppler waveform parameters were related to ankle/brachial systolic pressure (A/B) index and angiography in 75 patients with lower limb arterial occlusive disease (AOD). Doppler signals were obtained from ankle arteries, and following spectral analysis pulse rise time (PRT), systolic width (SW) and pulsatility index (PI) were calculated. All three waveform parameters were significantly correlated with A/B index, and a 20% reduction could be predicted with an accuracy of 93 to 80% (corrected for chance, kappa, 81 to 52%). A significant correlation was also found between the three Doppler parameters and the angiographic assessment, i.e. the non-diseased, single- and multisegmentally diseased limbs, however, the accuracy in diagnosing angiographic stenoses was not as good as when pressure measurement was used for reference. Thirteen of the patients had high ankle pressures despite significant angiographic stenoses, and generally the Doppler examination was normal in these cases. Considering the waveform parameters individually, PRT and SW demonstrated almost identical results when compared to pressure measurement as well as angiography, whereas PI seemed clearly inferior. It is concluded that simple Doppler waveform parameters may accurately predict the haemodynamic significance of proximal AOD. PMID- 2191880 TI - [Significance of the cytologic study of the gingiva proper in evaluating the condition of the periodontium]. PMID- 2191881 TI - [Management of cleft palate using the quadhelix expansion appliance]. PMID- 2191882 TI - Prediction of clinical diabetic nephropathy in IDDM patients. Alternatives to microalbuminuria? AB - This perspective deals with prediction of overt diabetic nephropathy in patients with insulin-dependent diabetes mellitus (IDDM). The role of elevated urinary albumin excretion rate (microalbuminuria) in predicting diabetic nephropathy has been emphasized by new follow-up studies. Development of severe kidney impairment was seen in a large percentage of patients with microalbuminuria, but with more intensive care for diabetic patients, this percentage may be falling. Herein, I analyzed alternatives to microalbuminuria in predicting kidney disease in diabetes. 1) Parental predisposition to hypertension is not seen in all studies and therefore may not be a decisive factor, and it cannot be used in prediction of nephropathy. 2) Prediabetic blood pressure may predict nephropathy in certain non-insulin-dependent diabetic patients, but elevated blood pressure seems to develop after early microalbuminuria and is likely to be an aggravating factor in established microalbuminuria in IDDM patients. 3) At the clinical diagnosis of IDDM, diabetic nephropathy cannot be predicted. 4) Glycemic control is poor in normoalbuminuric patients with later development of microalbuminuria, and multiple glycosylated hemoglobin measurements are therefore important. 5) In diabetes, glomerular hyperfiltration is associated with late nephropathy, but it alone cannot be the decisive factor, because hyperfiltration in nondiabetic individuals does not produce kidney disease, according to new long-term follow-up studies. 6) Studies of glomerular structure and ultrastructure have not yet documented predictive values for overt nephropathy, but further studies are in progress. 7) Isolated blood pressure elevation without microabuminuria (probably representing essential hypertension in diabetes) has not been predictive. 8) It is clear that elevation of serum creatinine is a very late and insensitive parameter, occurring only with pronounced proteinuria.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2191883 TI - Plasma C-peptide levels and clinical remissions in recent-onset type I diabetic patients treated with cyclosporin A and insulin. AB - Remission from insulin dependency in insulin-treated recent-onset type I (insulin dependent) diabetic patients can result from a partial recovery of insulin secretion, an improvement in tissue sensitivity to insulin, or both. The same hypothesis must be analyzed when remission occurs in cyclosporin A (CsA)-treated patients. In this study, plasma C-peptide levels were serially measured in the basal state and after stimulation in 219 recent-onset type I diabetic patients; 129 received CsA, and all patients were similarly monitored and insulin treated. The results were analyzed in view of the occurrence of remission. Remission was defined as good metabolic control in the absence of hypoglycemic treatment for greater than or equal to 1 mo. Remission occurred in 44% of the CsA-treated group and lasted for mean +/- SE 10.0 +/- 0.9 mo vs. 21.6% in the non-CsA-treated group with a duration of 4.4 +/- 0.8 mo. Plasma C-peptide levels were initially dramatically lower than normal in both groups in the basal and stimulated states. C-peptide levels increased significantly later, at 3 and 6 mo, in both groups. C peptide values were proportional to the rates of remission in both groups. In the non-CsA-treated group, C-peptide levels later decreased, and these patients inexorably relapsed to insulin dependency. In contrast, in the CsA-treated group, the initial recovery in insulin secretory capacity was maintained over the 18-24 mo of the study. Furthermore, higher remission rates and longer-lasting remission were obtained in patients who reached higher C-peptide levels at the 3rd mo of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2191884 TI - Metabolic effects of reducing rate of glucose ingestion by single bolus versus continuous sipping. AB - Modifying the rate of absorption has been proposed as a therapeutic principle of specific relevance to diabetes. To demonstrate clearly the metabolic benefits that might result from reducing the rate of nutrient delivery, nine healthy volunteers took 50 g glucose in 700 ml water on two occasions: over 5-10 min (bolus) and at a constant rate over 3.5 h (sipping). Despite similar 4-h blood glucose areas, large reductions were seen in serum insulin (54 +/- 10%, P less than 0.001) and C-peptide (47 +/- 12%, P less than 0.01) areas after sipping, together with lower gastric inhibitory polypeptide and enteroglucagon levels and urinary catecholamine output. There was also prolonged suppression of plasma glucagon, growth hormone, and free-fatty acid (FFA) levels after sipping, whereas these levels rose 3-4 h after the glucose bolus. An intravenous glucose tolerance test at 4 h demonstrated a 48 +/- 10% (P less than 0.01) more rapid decline in blood glucose (Kg) after sipping than after the bolus. Furthermore, FFA and total branched-chain amino acid levels as additional markers of insulin action were lower over this period despite similar absolute levels of insulin and C-peptide. These findings indicate that prolonging the rate of glucose absorption enhances insulin economy and glucose disposal. PMID- 2191885 TI - Synergistic effects of male sex and obesity on hepatic insulin dynamics in SHR/Mcc-cp rat. AB - The effects of obesity and sex on hepatic insulin metabolism were evaluated in the SHR/Mcc-cp rat. During in situ liver perfusion, insulin clearance rate (CLR) expressed per gram of liver tissue was reduced by 58 and 68% in obese females and males, respectively, compared with lean controls. Male sex resulted in CLR reductions of 46% in lean and 59% in obese animals. Obesity resulted in 50% reduction of insulin-receptor binding to isolated hepatocytes. In both lean and obese animals, male sex also resulted in a decrease of approximately 34% in insulin binding. Scatchard plots indicated that the reduction in insulin binding was primarily due to a decrease in number of cell surface receptors. Receptor mediated insulin degradation was 40% less in obese than lean animals. Male sex also resulted in 27% less insulin degradation relative to females. Receptor mediated insulin partitioning between four compartments (cell surface bound, internalized and/or cryptic, degraded, and dissociated or released intact), expressed as a percentage of the initial membrane-bound hormone, did not differ between the animal groups. Thus, male sex and obesity are independently and additively associated with a reduction in hepatic insulin clearance and a decrease in the number of cell surface insulin receptors with a proportional decrease insulin compartmentalization and degradation. This mechanism may partly account for the synergistic effects of male sex and obesity on the degree of hyperinsulinemia and insulin resistance and the predisposition to diabetes. PMID- 2191886 TI - Hypoglycemic thresholds for cognitive dysfunction in humans. AB - Nineteen healthy adult volunteers were studied to define the nature of and threshold for the cognitive dysfunction that occurs during insulin-induced hypoglycemia. The P300 cerebral event-related potential is an electrophysiological correlate of cognitive decision-making processes that can be measured in response to either an auditory or visual stimulus. P300 and reaction time (RT) were recorded from a visual stimulus under euglycemic conditions and at plasma glucose concentrations of 3.3 and 2.6 mM during insulin infusion in 10 subjects. Reducing plasma glucose levels to 3.3 mM was not associated with an increase in either the latency or amplitude of the P300 component or a change in RT. However, further lowering of plasma glucose to 2.6 mM resulted in an increase in the latency of P300 and a prolongation in RT. Similar changes were seen for the auditory P300 in experiments performed on 9 additional subjects in which both auditory and visual stimuli were presented. The prolongation of P300 did not correct immediately when plasma glucose was raised to basal levels with intravenous glucose but returned to normal 45-75 min later, after ingestion of a carbohydrate-containing meal. Analysis of another event-related potential, P140 (a measure of the sensory processes), showed no change in response to hypoglycemia. Prolongation of RT paralleled the prolongation of P300 latency, suggesting that motor processes were not altered. Therefore, hypoglycemia appears to induce abnormalities in decision-making processes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2191887 TI - Intrinsic cytotoxicity of natural killer cells to pancreatic islets in vitro. AB - BB rats develop spontaneous autoimmune insulin-dependent diabetes mellitus that is similar to human insulin-dependent diabetes. In this study, we used an in vitro islet cell cytotoxicity assay to study the possible role of natural killer (NK) cells and their soluble effector molecules in this disorder. First, the results demonstrated that in vivo treatment of acutely diabetic BB rats with anti asialogangliosideM1 (an NK cell antiserum) but not with anti-T-lymphocyte antibodies reduces spleen cell cytotoxic activity to islets in vitro. Flow microfluorometry (FMF)-sorting experiments were then used to confirm that the splenic cytotoxic effector cell in acutely diabetic BB rats is a CD8+/CD5- NK cell. Further analysis demonstrated that both FMF-sorted NK cell populations from Wistar-Furth rats and unfractionated spleen cells from athymic nu/nu rats with high intrinsic NK cell activity also exhibit high islet cell cytotoxic activity in vitro. Finally, we found that the kinetics and differential cytotoxic activity of NK cells toward islets in vitro could be mimicked by NK cell culture supernatants containing high levels of NK cytotoxic factor (NKCF). The islet cytotoxic activity of these culture supernatants was specifically inhibited by the addition of anti-NKCF monoclonal antibody. These results demonstrate that NK cells from diabetic and nondiabetic rats are cytotoxic to islet cells in vitro. They further suggest that this cytotoxic effect may be mediated in part through the production and release of soluble factors such as NKCF. PMID- 2191888 TI - Improvement with metformin in insulin internalization and processing in monocytes from NIDDM patients. AB - This study investigated the relative effect of obesity alone and in combination with non-insulin-dependent diabetes mellitus (NIDDM) on the intracellular processing of insulin and evaluated the effect of metformin therapy on this process. Monocytes from 11 obese hyperinsulinemic subjects, 13 obese hyperinsulinemic NIDDM patients, and 7 nondiabetic control subjects were incubated with A14-125I-labeled insulin for 60 min at 37 degrees C, and intracellular insulin degradation was characterized by high-performance liquid chromatography. Total cell-associated insulin (insulin binding) and internalized and degraded insulin were decreased in obese subjects and significantly decreased in obese NIDDM patients compared with nondiabetic control subjects. In NIDDM patients, intracellular insulin degradation was inversely correlated with fasting plasma glucose (P less than 0.01). Eight obese subjects and 9 obese NIDDM patients were restudied after 4 wk of therapy with metformin (850 mg twice a day). Plasma levels of the drug were superimposable in the two groups. Metformin therapy did not change glucose and insulin levels in obese subjects but caused a decrease in blood glucose in obese NIDDM patients. Total cell-associated radioactivity (insulin binding) significantly increased in both groups (P less than 0.01). On the contrary, internalized radioactivity increased (0.83 +/- 0.3 vs. 1.31 +/- 0.35%, P less than 0.01), and similarly, insulin degradation was enhanced (54.6 +/- 8.9 vs. 74.22 +/- 9.15%, P less than 0.01) only in monocytes from obese NIDDM patients. However, the levels of these parameters were still lower than in control subjects (internalization, 2.94 +/- 0.68%; degradation, 93.03 +/- 3.7%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2191889 TI - Lack of islet amyloid polypeptide regulation of insulin biosynthesis or secretion in normal rat islets. AB - We examined the effects of rat islet amyloid polypeptide (IAPP) on insulin biosynthesis and secretion by isolated rat islets of Langerhans. Culture of islets for 24 h in the presence of 10(-6) M IAPP and 5.5 mM glucose had no effect on insulin mRNA levels. Similarly, the rates of proinsulin biosynthesis were not altered in islets incubated in 10(-4)-10(-9) M IAPP and 5.5 mM glucose, nor was the rate of conversion of proinsulin to insulin changed at 10(-6) M IAPP. Addition of 10(-5) M IAPP to islets incubated in 11 mM glucose decreased the fractional insulin secretion rate; however, the secretion of newly synthesized proinsulin and insulin was not affected. These data indicate that it is unlikely that IAPP is a physiologically relevant modulator of insulin biosynthesis or secretion. PMID- 2191890 TI - Is routine vitamin E administration justified in very low-birthweight infants? AB - Analysis of nine randomised controlled trials of prophylactic vitamin E supplementation in very low-birthweight infants (less than 1500g) showed no statistically significant reduction in the incidence of acute retinopathy of prematurity. There was a significant reduction (49 per cent) in the incidence of intraventricular haemorrhage, but no clear evidence for a corresponding reduction in intracerebral haemorrhage and no reduction in the incidence of haemorrhage confined to the germinal matrix. By combining the estimated reduction with the known incidence of long-term neurological disability associated with intracranial haemorrhage alone, it was shown that only 1.5 per cent (point estimate) and not more than about 4 per cent of all very low-birthweight infants are likely to benefit from routine vitamin E supplementation. In view of this, and data suggesting toxicity of vitamin E at concentrations close to those considered therapeutic, the routine use of vitamin E in very low-birthweight infants is not justified on present evidence. Only large randomised trials can establish whether currently used vitamin E preparations do more good than harm. PMID- 2191891 TI - The effect of stress and exogenous cortisol on receptor-like binding of cortisol in the liver of rainbow trout, Oncorhynchus mykiss. AB - Cortisol binding has been identified in cytosols prepared from rainbow trout liver. Binding is of high affinity (kD = 5.1 +/- 0.2 nM, n = 23) low capacity (Nmax = 197 +/- 12 fmol mg-1 protein, n = 23), and high specificity, only dexamethasone, cortisol, and Ru38486 being efficient in displacing bound [3H]cortisol. Binding is not due to contamination by blood because plasma displayed no affinity for cortisol under the assay regime employed here and, although whole blood cytosol does specifically bind cortisol, the degree of contamination is demonstrably too low to account for the levels of binding detected in liver cytosol. No specific binding of [3H]cortisol could be detected in liver nuclear extracts, although the simultaneous assay for nuclear estradiol binding sites was positive. Rainbow trout stressed by confinement displayed a significant reduction in cytosolic [3H]cortisol-binding capacity (with no concomitant detectable appearance of binding within nuclear extracts), 96-hr confinement eliciting a 40% depression in binding capacity relative to unstressed fish. The administration of cortisol via intraperitoneal implants also reduced, significantly, the number of hepatic-binding sites. The results are discussed with reference to anomalies in reported characteristics of teleost glucocorticoid receptors and the phenomenon of down-regulation observed in some mammalian systems. PMID- 2191892 TI - Nocturnal increase in pineal melatonin production in two lemming species, Dicrostonyx hudsonius and D. groenlandicus. AB - Pineal N-acetyltransferase (NAT) activity and melatonin levels and thyroxine 5' deiodinase (5'D) activity in brown adipose tissue (BAT) were compared during the day and night in two species of lemmings, Dicrostonyx hudsonius and D. groenlandicus. In both species, NAT and melatonin exhibited significant night time increases in the pineal gland. Thyroxine 5'D activity in BAT did not show a statistically significant day-night difference in either species of lemming, suggesting the night-time rise in melatonin does not induce a similar increase in BAT 5'D. PMID- 2191893 TI - Vasopressor and depressor effects of native angiotensins and inhibition of these effects in the Japanese quail. AB - The amino acid sequence of angiotensin I (ANG I) from the Japanese quail, Coturnix coturnix japonica, obtained from incubation of homologous plasma and kidney extract was determined as H-Asp-Arg-Val-Tyr-Val-His-Pro-Phe-Ser-Leu-OH. A bolus, intravenous injection of native ANG I or of ANG II induced an immediate vasodepressor response and a subsequent vasopressor response in quail which has been lightly anesthetized with urethane (0.75 g/kg). The values for ED50 for the vasopressor and depressor effects of ANG II were 85 and 113 pmol/100 g body weight, respectively. The extent of the hypotension was dependent on the arterial pressure prior to injection. The effects of ANG I and II on heart rate were variable. Human [Asp1, Ile5, His9] ANG I and II were almost as potent as their quail counterparts with respect to the cardiovascular effects, but eel [Asn1, Val5, Gly9]ANG I and II were less than half as potent. Human ANG III had little effect on arterial pressure in the quail. A bolus injection (100 micrograms/100 g) or infusion (1 micrograms/100 g/min) of [Sar1, Ile8] ANG II almost abolished the cardiovascular effects of ANG I and II, but [Sar1, Ala8] ANG II and [Sar1, Thr8] ANG II, which are effective inhibitors in mammals, had no inhibitory effects. The vasopressor and depressor effects of ANG I were abolished, while those of ANG II were slightly enhanced, after injection (100 micrograms/100 g) or infusion (1 micrograms/100 g/min) of SQ14225, whereas des-Pro2 bradykinin and bradykinin potentiator B, which are effective inhibitors of ANG I converting enzyme in mammals, failed to inhibit the effect of ANG I. These results indicate that vascular ANG II receptors and ANG I converting enzyme in the quail may be different from those in mammals. PMID- 2191895 TI - [Cloning and structural-functional analysis in Escherichia coli of genes of glutamate-producing corynebacteria controlling biosynthesis of amino acids of aspartic acid series]. AB - A library of EcoRI DNA fragments from Brevibacterium flavum was constructed using plasmid vector. The genes complementing ThrA2 and ThrB mutations in Escherichia coli were identified in the library. The gene thrA2 of B. flavum codes for mutant enzyme homoserine dehydrogenase insensitive to inhibition by threonine. The genes thrA2 and thrB are localized wihtin the EcoRI fragment 4.1 kb long and are expressed under the control of their own promoters in E. coli cells. Structural and functional analysis of cloned C. glutamicum gene ilvA was performed. The gene of C. glutamicum complemented ilvA mutation in E. coli and appeared to be localized within the EcoRI--SacI DNA fragment 1.6 kb in size. Using E. coli minicells we have demonstrated that the gene ilvA of C. glutamicum controls the synthesis of polypeptide of relative molecular mass 50 kD. PMID- 2191894 TI - Aromatization mediates aggressive behavior in quail. AB - Although testosterone (T) stimulates aggressive and reproductive behaviors in males of many vertebrate species, it is now known that the full expression of T action in the brain requires aromatization to estradiol (E2) and subsequent interaction of locally formed E2 with nuclear estrogen receptors. In experiments reported here, we used a behavioral test which quantifies the response of an individual male Japanese quail (Coturnix coturnix japonica) to the visual stimulus of a conspecific. We have called this behavior aggression because it shares many features in common with traditional measures of aggression, e.g., predicting dominance and subordinance. Nevertheless, the behavior probably also combines a complex steroid-sensitive masculine behavior. The advantage of this test is that it allows the discrimination of individual differences in masculine behavior but avoids fighting and sexual encounters per se, thereby reducing effects of learning, a problem with previous tests of avian aggression. In addition, this test has been applied usefully to identify neuroendocrine correlates to male behavior. Using this test, the arousal of reproductively inactive males (hereafter referred to as aggression) is activated by administration of T or estradiol benzoate (EB), but not by 5 alpha dihydrotestosterone (DHT). T-induced aggression was blocked by the aromatase inhibitor 4-hydroxyandrostenedione (OHA), an effect partially reversed by treatment with EB. In addition, OHA or the estrogen receptor blocker CI-628 reduced aggressiveness of reproductively active males whereas the androgen receptor blocker flutamide had no effect. Results with the 5 alpha-reductase inhibitor N,N-diethyl-4-methyl-3-oxo-4-aza-5 alpha-androstane-17 alpha carboxyamide (4-MA) were equivocal. Additionally, treatment of reproductively inactive quail with T or E2 but not DHT increased aromatase activity in the hypothalamus-preoptic area (HPOA). We conclude, therefore, that T to E2 conversion is essential for the activation of aggressiveness in this species. Although locally formed estrogen exerts its effects on aggression in part by increasing activity of aromatase per se, analysis of the time course of behavioral induction or suppression by the various treatments suggests that the response has multiple components, including both short latency, receptor independent and long latency, receptor-dependent events. PMID- 2191896 TI - [The effect of specific mutation crp a in the genetic locus of receptor protein cAMP (CRP) on the expression of Escherichia coli K-12 deo-operon]. AB - Expression of the deo operon of Escherichia coli is subjected to double negative control by DeoR and CytR repressors and to the positive control by cAMP-CRP complex. However, sensitivity of the deo operon to catabolite repression is only revealed in bacteria with disrupted synthesis of the CytR protein, since the function of the latter is to prevent CRP activation of the deo operon transcription. In the present work we have studied the influence of crpa specific mutation at the genetic locus of CRP protein on the expression of the deo operon of E. coli. It has been found that the presence of crpa mutation in bacterial genome completely eliminates CytR repression of the deo operon, so that activation of Deo enzymes synthesis by cAMP-CRPa complex becomes possible, even in the presence of CytR. Besides, the modified CRPa protein appears to block the activity of catabolite-sensitive deoPO2 promoter of the deo operon under conditions of cAMP deficiency, which is manifested in the two-fold decrease of deoR derepression in the crpa cells, as compared to the wild type bacteria during the growth on glucose containing medium. It has been supposed that both effects are due to increased affinity of the modified CRPa protein to the specific sites of catabolite sensitive promoters, as compared to the wild type CRP protein. PMID- 2191897 TI - [The effect of small concentrations of antibiotics blocking the synthesis of bacterial cell wall on the permeability of Escherichia coli cell wall for plasmid DNA]. AB - Short treatment of Escherichia coli cells with antibiotics disturbing synthesis of bacterial cell wall in small concentrations renders the cells capable of absorbing foreign plasmid DNA. A novel express-method for transformation of E. coli cells by plasmid DNA has been developed on the basis of the results obtained. The whole procedure can be performed at room temperature. Depending on cell strain and the plasmid size, the efficiency of transformation can vary from 1.10(4) to 5.10(5) transformants per 1 mkg of DNA. The method suggested improves significantly the every-day work aimed at constructing plasmids. PMID- 2191898 TI - [Increase in stability of the recombinant phage M13 carrying Escherichia coli genes rpIJL by reducing expression of cloned genes]. AB - A recombinant phage mp9MW/rpoB containing the BglII-B fragment of the Escherichia coli rplJL-rpoBC gene cluster was constructed on the basis of filamentous phage M13. Stability of the phage was increased by insertion of a transcription terminator t beta' which blocked transcription of cloned genes from the Plac of the vector. PMID- 2191899 TI - Helping Medicare beneficiaries choose health insurance: the illness episode approach. AB - Lacking objective, comprehensible information about health care coverage options, Medicare beneficiaries rarely understand the consequences of alternative purchasing decisions. We describe the Illness Episode Approach, a method providing information on Medicare itself, Medigap policies, and HMOs. The method presents calculations of seniors' out-of-pocket costs under different insurance options for 13 common illnesses. PMID- 2191900 TI - Disposition at discharge and 60-day mortality among elderly people following shorter hospital stays: a population-based comparison. AB - This study examines whether shorter hospital stays following the introduction of Medicare's Prospective Payment System have been accompanied by increased mortality or an increased rate of discharge to nursing homes. An examination of hospitalizations for all elderly residents of Olmsted County, MN (N = 5,854) for 1980, 1985, and 1987 demonstrates significant increases in 60-day mortality and nursing home transfers after this system began. These increases, however, are largely explained by differences in risk factors other than length of stay, such as patient age, gender, disease severity, and complexity. PMID- 2191901 TI - Old age in America represented in nineteenth and twentieth century popular sheet music. AB - This paper examines American popular sheet music published between 1830 and 1980 as a source for understanding popular perceptions and feelings about aging and old age. From a private collection of over 300 pieces of sheet music related to aging, two forms of representation of popular sentiments are reviewed: cover art and lyrics. A substantial majority present negative rather than positive views of aging and old age. PMID- 2191902 TI - Quinones, semiquinone free radicals and one-electron transfer reactions: a walk in the literature from Peru to S.O.D. PMID- 2191903 TI - Bioreductive activation of quinones: redox properties and thiol reactivity. AB - Redox properties and thiol reactivity are central to the therapeutic and toxicological properties of quinones. The use of other physicochemical parameters to establish predictive relationships for redox properties of quinones is discussed, and attention drawn to situations where such relationships may be unreliable. The rates of reaction of semiquinone radicals with oxygen, including those of chemotherapeutic agents such as mitomycin and the anthracyclines, can be predicted with reasonable confidence from the redox properties. The reactions of quinones with thiols such as glutathione produces reduced quinones and radicals, but the reactions are complex and all the features are not well understood. PMID- 2191904 TI - Interactions of vitamin E with free radicals and membranes. AB - alpha-Tocopherol performs an antioxidant role in biological membranes by acting as a one-electron reductant. In micellar solutions it has been observed by pulse radiolysis that the micellar charge has a pronounced effect on the rate constant for repair of organic free radicals by alpha-tocopherol. The interactions between alpha-tocopherol and model bilayer lipid membranes have been studied by fluorescence spectroscopy. Quenching of alpha-tocopherol fluorescence by acrylamide and some n-doxyl stearates shows the transverse distribution of alpha tocopherol in membranes to be affected by the physical state of the membrane lipids and by the salt concentration in the aqueous phase. Time-resolved fluorescence depolarization measurements, with a diphenylhexatriene-phospholipid conjugate as probe, demonstrate an increase in bilayer order parameter on incorporation of alpha-tocopherol into a membrane. PMID- 2191905 TI - Successful pregnancy following treatment of primary malignant lymphoma of the uterine cervix. AB - A case of primary histiocytic lymphoma in the uterine cervix of a 22-year-old nulligravid woman is reported. To avoid surgical or radiological castration she received six courses of combination chemotherapy (cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, vincristine 2 mg all iv on Day 1 and then together with oral prednisone 50 mg twice daily on Days 1-5). Approximately 20 months after therapy she delivered a healthy child. Six years have passed since primary treatment was initiated. No evidence of recurrent lymphoma has been observed. PMID- 2191906 TI - Metastatic basal cell carcinoma of the vulva. AB - Basal cell carcinoma of the vulva is rare and was initially thought to be nonmetastasizing; however, there are four reports in the literature of metastasis to regional lymph nodes. We present the case report of a fifth patient with well documented metastasizing basal cell carcinoma of the vulva with a brief discussion on clinical presentation, treatment, and positive response to preoperative radiation which could make radical surgery unnecessary. PMID- 2191907 TI - Squamous cell carcinoma antigen and carcinoembryonic antigen levels as prognostic factors for the response of cervical carcinoma to chemotherapy. AB - Between January 1986 and December 1988, 36 patients with primary advanced or recurrent cervical carcinoma were treated with cytostatic drugs in our department. Treatment at first was a combination of cisplatin and etoposide. After August 1987, a combination of carboplatin and ifosfamide was used. In all patients showing primary response to therapy, the squamous cell carcinoma antigen (SCC) and carcinoembryonic antigen (CEA) levels fell rapidly to normal after one or two cycles. In contrast, clinical remission was not obtained in those patients with levels which remained high or rose again following an initial decrease. Chemotherapy is often the only available therapy for advanced cervical carcinoma or recurrent disease, although the results of treatment, especially in squamous cell carcinoma, remain poor. The course of the SCC or CEA levels can help to decide whether the patient would profit from a continuation of the therapy. With the tumor markers, treatment can be individualized so that, above all, cases of therapy failure or further tumor progression can be detected early and the patient can be spared the severe side effects of the treatment. PMID- 2191908 TI - Benefit of external irradiation in pathologic stage I endometrial carcinoma: a prospective clinical trial of 605 patients who received postoperative vaginal irradiation and additional pelvic irradiation in the presence of unfavorable prognostic factors. AB - Six hundred and five cases of endometrial carcinoma, pathologic stage I, without definable extrauterine disease were initially treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy, followed by high-dose-rate iridium-192 irradiation of the vagina. External irradiation of the pelvis was performed only for patients with poor prognostic factors. Five-year survival was calculated by the product-limit method of Kaplan and Meier. Three hundred and forty-eight patients with tumor invasion of the inner third, of any tumor grade, received postoperative vaginal irradiation only. Twenty-eight patients with grade 1 tumor invasion of the middle third received vaginal irradiation only. One hundred and six patients with grade 2 or 3 tumor and infiltration of the middle third received vaginal and external irradiation of the pelvis. One hundred and twenty-three patients with deep muscle invasion of the external third of the myometrium received vaginal and pelvic irradiation. Differences in survival figures were not significant. Survival of the treatment group with good prognosis who received vaginal irradiation alone (91%) was similar to that of the group with poor prognosis who received additional pelvic irradiation (87.7%). Despite the unfavorable situation of patients with poor prognostic factors, treatment results after additional external irradiation were relatively equal to the results for patients with good prognostic factors who had not received external irradiation. Therefore, the benefit of external irradiation in patients with stage I endometrial carcinoma with unfavorable prognostic factors seems evident. PMID- 2191909 TI - [Modification of the behavioral effects of drugs after repeated administration- special reference to the reverse tolerance of amphetamines]. AB - It has been well-known that a chronic abuse of amphetamines induces schizophrenia like psychotic symptoms, namely amphetamine psychosis. When amphetamines are repeatedly administered to rodents, a reverse tolerance (behavioral sensitization) to the ambulation-increasing and/or stereotypy-producing effect is observed. The process of the reverse tolerance is affected by various factors. A clear reverse tolerance is produced when optimal doses of the drug (2 mg/kg, s.c. for mice, and 0.5-1 mg/kg, s.c., for rats) is administered at intervals of longer than 1 day rather than a shorter interval. Furthermore, the animal has to be put into a freely mobile situation during the presence of the acute drug effect. A cross reverse tolerance is observed between certain types of drugs that show an ambulation-increasing effect, although the potencies are different among the drugs. A reverse tolerance to the stereotypy (in particular sniffing and head bobbing)-producing effect is also observed when comparatively higher doses of methamphetamine are repeatedly administered. The process is qualitatively identical with the reverse tolerance to the ambulation-increasing effect produced by the repeated administration of comparatively smaller doses. The reverse tolerance, once established, to both ambulation-increasing and stereotypy producing effects is almost irreversible even with various treatments such as repeated post-treatment with antipsychotics. The characteristics of reverse tolerance to methamphetamine in animals might be closely correlated to the amphetamine psychosis in humans. It is also necessary to search for a method that effectively reduces the established reverse tolerance to amphetamines. PMID- 2191910 TI - [Adenosine and methylxanthines in the central nervous system--on their significance for psychiatry and neurology]. AB - In the last 15 years the central effects of adenosine and its importance for neurology and psychiatry have increasingly become an object of investigation. Physiology and metabolism of adenosine have been examined by different research groups. The effects of adenosine in the central nervous system and the various mechanisms of these effects have been described by electrophysiologic methods. The inhibition of the release of several neurotransmitters through adenosine has already been described 10 years ago. In this review studies on binding sites for adenosine receptor ligands are discussed thoroughly. The properties and the highly specific distribution of the distinct receptor subtypes are described. For the functioning of the adenosinergic system the different interactions with other centrally active substances such as benzodiazepines, barbiturates, neuroleptics, anti-depressants, opiates, alcohol and carbamazepine have turned out to be of interest. The results of neuropsychiatric investigations on methylxanthines, which are antagonists at the adenosine receptor, are widely considered. Finally the discussion on the importance of the adenosinergic system in different neurological and psychiatric diseases is summed up. The particular significance of adenosine in the modulation of dopaminergic functions is emphasised. PMID- 2191911 TI - [Ethical and legal aspects of the use of placebos in research and practice]. AB - The discussion of ethical and legal problems concerning placebo application is suggested as an essential constituent of modern placebo research. Implications of distinctions between inadvertent and intended placebo applications and between single case and sample applications of placebos are examined. Implicit hypotheses of placebo applicators (investigators, practitioners) on the indications and contra-indications of placebos are confronted with empirical data which are still limited, however. Differentiation between several levels of information given the placebo recipient about the real nature of the placebo application is suggested and pro and contra of each level will be discussed in detail. In the following ethical and legal aspects of placebo application in practice (with clinical patients) and in research (sample tests) are elaborated. Finally actual issues of law concerning placebo applications in the Federal Republic of Germany are discussed. PMID- 2191912 TI - [Dementia in hypothyroidism]. AB - Hypothyroidism is one of the most frequent causes of potentially reversible dementia. According to present knowledge, symptoms of mental impairment begin insidiously and show a slow progression. They may precede the typical somatic manifestations of thyroid dysfunction. Almost complete remission of dementia may be expected from hormone substitution when the diagnosis is established early. The pathogenetic mechanisms which may have important implications for other forms of dementia are still imperfectly understood. PMID- 2191913 TI - [Normal pressure hydrocephalus. An evaluation 25 years following the initial description]. AB - A quarter of a century after the first description of a condition known as "normal pressure hydrocephalus", there no longer exists serious doubt about the existence of this disease nor about the possibility of treating it surgically with success. Nevertheless, there is still no general agreement on the exact definition of this condition, nor is there confirmed knowledge regarding its pathogenesis. Approximately half of the cases still are designated "idiopathic" in as much as physicians have no clear concept of its etiology. Some progress has been reached concerning the indication for operation: the "resistance to outflow" of cerebrospinal fluid can be measured now exactly by fluid infusion tests and seems to be a valuable predictor of outcome after shunting procedures. Reviewing world literature of the past 25 years reveals: the most important symptom of normal pressure hydrocephalus is not dementia, but disturbances of gait. Patients suffering from dementia, but not from gait-disturbances, do not gain from cerebrospinal fluid shunting and do not need to be investigated by invasive diagnostic procedures. In patients who suffer from gait-disturbances with or without dementia, with or without urinary incontinence, and in whom computed tomography reveals enlargement of ventricles without pronounced cortical atrophy, there should be a measurement of intracranial pressure and of the resistance to cerebrospinal fluid outflow. PMID- 2191914 TI - [Eosinophilic granulocytes in the cerebrospinal fluid]. AB - The first section of the paper presents the morphology, structure and function of the eosinophilic granulocytes, while the second part deals with major neurologic diseases in which eosinophils are present or represent significant findings. These data are compared with the results of the author's own examinations of 1,000 unselected cerebrospinal fluid (CSF) samples. Eosinophils appeared usually in conjunction with infection, followed by foreign body inflammation. If the proportion of eosinophils exceeds 4%, the condition is termed CSF-eosinophilia, which usually develops in the presence of foreign bodies. However, infection may produce similar findings, especially in parasitic disease, and tumours of the central nervous system occasionally present with CSF eosinophilia. PMID- 2191915 TI - Unsupervised classification of cell images using pyramid node linking. AB - In this communication we describe a segmentation technique which combines two properties in an iterative and hierarchial matter to correctly segment and classify the given cell images. The technique is applied to digital images taken from microscope slides of cultured rat liver cells, and the goal is to classify these cells into one of three possible classes. The first class cells (I) are morphologically normal and stain the darkest. The second class cells (II) are slightly damaged showing both nuclear and cytoplasmic swelling with resultant lessening of staining affinity. The third class cells (III) are markedly damaged as demonstrated by the presence of cytoplasmic vacuolization, or are completely disintegrated. First class cells are classified by taking advantage of their staining affinity; the original gray level image is segmented into four gray levels. The darkest is then classified as type I. Type III cells are classified by using high business as a characteristic; the standard deviation of the original image is segmented into four business levels. The highest level is classified as type III cell. Assuming only the three cell types are present in any given image, the remaining non-background unclassified pixels are determined to belong to type II cells. PMID- 2191916 TI - Structure and properties of fibronectin. PMID- 2191917 TI - The phenotypic heterogeneity of mouse thymic stromal cells. AB - Sixteen monoclonal antibodies (mAb) were produced against mouse thymic stromal elements. These mAb fell into two groups of reactivity: (i) thymic epithelial markers (screened and presented according to the guidelines proposed in the 1989 Rolduc Thymic Epithelial Workshop); and (ii) non-epithelial thymic markers. Specificities of these mAb included extensive subpopulations of both epithelial and non-epithelial thymic stromal cells, as well as isolated stromal cells, demonstrating some of the complex microspecificities in existence within the thymic microenvironment. Furthermore, six of these mAb demonstrated shared antigenicity between thymocytes and thymic stromal cells, revealing greater similarities than previously recognized between these two components. Three mAb detected antigens illustrating three consecutive layers of the blood-thymus barrier: the vascular endothelium; connective tissue of the capsule and perivascular spaces; and the connective tissue associated with the basal laminae lining these regions. This study illustrates unequivocably that there are indeed complex and varied microenvironments existing within the thymus, and emphasizes the need for reclassification of these cells. PMID- 2191918 TI - HLA-DR peptide inhibits HIV-induced syncytia. AB - The infectivity of the human immunodeficiency virus (HIV) is related to the structure of its envelope protein, gp160, which is responsible for viral entry. We considered the possibility that a structural homology between gp160 and major histocompatibility complex (MHC) molecules might be associated with the extraordinary affinity that gp120 has for its receptor, CD4. Amino acid sequence comparisons revealed five regions of structural similarity between the HLA-DR beta molecule and gp160. The DR2 beta synthetic peptides containing these regions were examined for their ability to block HIV-induced syncytia formation using a 51Cr release assay. The peptide beta 141-155 inhibited the formation of syncytia whereas the other four DR beta peptides with gp160 similarity did not. Our results indicate that this region in gp120, which is similar to an HLA-DR region, is crucial to T cell-gp120 interactions, and should be considered in the design of future vaccines. PMID- 2191919 TI - Energy expenditure in the obese: is there a thrifty gene? AB - Seven to eight thousand Pima Indians are presently living in the southwestern desert of Arizona. The prevalence of type II diabetes in this population exceeds 45% and more than 75% of the Pimas are obese. In 1962, Neel proposed that obesity in populations like the Pima Indians might be the expression of a "thrifty gene" which becomes detrimental with progress. Since 1982, longitudinal studies have been conducted including measurements of metabolic rate in 200 non-diabetic Pima Indians and have shown that 1) at any given body weight and body composition, there is quite a large variability in the resting metabolic rate which is not accounted for by intra-individual variability or errors of the methods; 2) metabolic rate after adjustment for body composition and body weight is a familial trait; 3) a low metabolic rate is a risk factor for body weight gain; 4) in response to body weight gain, there is a "normalization" of the resting metabolic rate. These studies are the first showing that a "thrifty" metabolic rate can play a role in the development of obesity. PMID- 2191920 TI - Risk of HIV infection from former blood donations of donors found to be HIV antibody-positive in blood bank routine testing. "Look-back" study in German Red Cross Blood Banks in the FRG. AB - Recipients of blood given by 52 repeat blood donors found to be positive by Western blot analysis for anti-HIV from April 1985 to December 1987, among a total of 1.6 million blood donors in the German Red Cross Blood Banks in the FRG, were investigated. Of 149 recipients identified, 76 (51%) had died. Ten recipients refused to be tested. Of those recipients who were tested at least 5 months after transfusion, 46 were HIV antibody negative and 17 were Western blot positive. In 14 of the HIV antibody-positive recipients, transfusion was given during the period from 1982 to the begin of routine testing in 1985. Three recipients of HIV antibody-negative donations were subsequently identified as HIV positive. The blood had been donated a median of 3 months before HIV antibodies were detected in the donors. From a total of 3 million donations since testing has been introduced, the risk of HIV transmission in tested blood is 1:1 million in our donor population where the HIV antibody prevalence (in Western blot) is about 1 per 100,000 donations/donors. PMID- 2191921 TI - Grass pollen allergens: detection on pollen grain surface using membrane print technique. AB - A microtechnique is described to visualize pollen allergens by making prints from the surface of mature grains on nitrocellulose membrane. The allergen Lol p I is detected by specific monoclonal antibodies or specific IgE from sera of grass pollen-allergic patients, visualized by the immunoperoxidase method. This technique offers the potential to study the distribution of individual allergens in aerobiology samples by bright-field microscopy, and to determine the sensitivity spectra of allergic individuals to known and unknown pollen sources. PMID- 2191922 TI - Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids. AB - 9-Fluorenylmethoxycarbonyl (Fmoc) amino acids were first used for solid phase peptide synthesis a little more than a decade ago. Since that time, Fmoc solid phase peptide synthesis methodology has been greatly enhanced by the introduction of a variety of solid supports, linkages, and side chain protecting groups, as well as by increased understanding of solvation conditions. These advances have led to many impressive syntheses, such as those of biologically active and isotopically labeled peptides and small proteins. The great variety of conditions under which Fmoc solid phase peptide synthesis may be carried out represents a truly "orthogonal" scheme, and thus offers many unique opportunities for bioorganic chemistry. PMID- 2191923 TI - Solitary benign schwannoma in the psoas muscle. AB - Solitary benign schwannoma in the psoas muscle is extremely rare. Here we present a case report of a woman who had solitary benign schwannoma in the psoas muscle not associated with von Recklinghausen's disease. This is the fifth case reported in the literature. PMID- 2191924 TI - Non-prostatic malignant disease mimicking prostatic cancer. AB - Three patients with pelvic tumours (2 cases of pelvic sarcoma and 1 case of metastatic bronchial carcinoma) presented with symptoms and signs suggestive of prostatic carcinoma. Transrectal ultrasonic scanning with perineal biopsy facilitated the diagnosis. The prognosis of pelvic sarcoma was poor following radiotherapy. PMID- 2191925 TI - [Pneumonia--clinical aspects and therapy]. PMID- 2191926 TI - [Airway obstruction and inflammation]. PMID- 2191927 TI - [Pneumoconioses--current status of knowledge]. PMID- 2191928 TI - [The diagnosis of pleural effusion]. PMID- 2191929 TI - [Dyspnea]. PMID- 2191930 TI - [HIV infection and tuberculosis]. PMID- 2191931 TI - [Primary adenocarcinoma of the duodenum]. PMID- 2191933 TI - Distinguished Scientist at the AFIP, 1988-1989. PMID- 2191932 TI - Immunolocalization of type VI collagen in developing and healing rabbit cornea. AB - We have localized type VI collagen in normal developing and corneal scar tissue. Indirect immunofluorescence showed that type VI collagen was distributed throughout the normal stroma and most of the scar. No fluorescence was detected along the posterior margin of the scar and in a retrocorneal membrane continuous with the scar. Since the corneal endothelium in rabbits contributes to the formation of scar tissue and retrocorneal membrane, our observations suggest that the endothelium does not synthesize type VI collagen. Indirect immunoelectron microscopy showed that type VI collagen was located abundantly between collagen fibrils as fine filamentous structures containing beads with a periodicity of 100 nm, consistent with published observations of other tissues. Because these filaments are more prominent when stained with ruthenium red, and predigestion of tissue with Chondroitinase ABC enhances binding of monoclonal antibody to type VI collagen, proteoglycans probably are associated with this collagen in the cornea. Ultrastructural observations supported by previous biochemical analyses show that the proportion of type VI collagen to fibrillar collagen is smaller in scar tissue compared with fetal cornea. The abundance of type VI collagen and its distribution and association with proteoglycans in rabbit corneal tissues suggest that this macromolecule plays a role in the tensile strength and transparency of the stroma. PMID- 2191934 TI - Ultrasound-guided percutaneous injection of ethanolamine oleate for hypersplenism. An experimental study in dogs. AB - In order to evaluate a possible therapy for hypersplenism, an experiment with animals was done. In nine dogs, 0.6 ml/kg body weight of 5% ethanolamine oleate was injected percutaneously into the spleen under ultrasound guidance. The injection was repeated three times at intervals of 1 week. Three dogs each were killed at 1, 4, and 8 weeks after the final injection. All dogs tolerated the procedure well and lived until they were killed. The platelet count and leukocyte count increased after the injections, and remained higher than the pretreatment level until death. This effect probably is due to depressed splenic function. The autopsy showed 40% of the spleen to be infarcted with complete destruction of the normal structure. No serious complications occurred. In addition, injection of ethanolamine oleate in six fully heparinized dogs showed that there was little risk of hemorrhage. Ultrasound-guided percutaneous injection of ethanolamine oleate might be a simple and effective therapy for hypersplenism. PMID- 2191935 TI - Detection and measurement of simulated early rheumatoid lesions of the hand using digital subtraction radiography. AB - The ability of digital subtraction radiography, a new technique to detect and quantify small bone lesions, is demonstrated. Discrete lesions in the metacarpals of cadaver hands simulated erosive bone loss. Radiographs made before and after removal of bone were digitized and subtracted. Density changes on subtraction images were determined, and bone loss was estimated by an automatic procedure that compared changes in radiographic density with a calibration wedge included in the radiographs. Comparison of estimated bone loss with the weight of bone removed showed reproducible detection and measurement of bone lesions as small as 4.6 mg, a size undetectable using current radiographic methods. Subtraction radiographs of bone chips overlaid on the hand of a volunteer indicated detection limits were similar in vivo. This technique enhanced the radiographic visibility of erosive lesions and thus has the potential to improve the detection of subtle bone changes in clinical settings. PMID- 2191937 TI - Artificial neural networks. PMID- 2191936 TI - Dynamic digital subtraction evaluation of regional pulmonary ventilation with nonradioactive xenon. AB - A method of evaluating pulmonary ventilation with a 57-cm image intensifier/television (II/TV) digital chest system is reported. With this method, the patient inhales a mixture of xenon and oxygen gases while dynamic imaging of the chest is done. Images of the airways and ventilated portions of the lungs are obtained by subtraction of images acquired before and after the xenon-oxygen mixture is administered. The feasibility of the method was evaluated by studies with xenon-filled tubes, an airway phantom, and a ventilation phantom. The results indicate that tubes larger than 3.2 mm in diameter are detectable at a xenon concentration of 41%, and that gas flow and flow distribution can be examined after image subtraction. If background subtraction is incomplete because of motion, the visibility of small airways is reduced greatly, although unventilated regions can still be delineated. The initial evaluation of this technique included imaging a healthy volunteer during xenon inhalation. PMID- 2191938 TI - A placebo-controlled crossover trial of nimodipine in pediatric migraine. AB - An 8-month, double-blind, placebo-controlled crossover trial was carried out on the use of nimodipine in migraine prophylaxis in 37 patients aged 7 to 18 years old. After a 4-week medication-free run-in period, 19 subjects (Group 1) received a placebo while 18 (Group 2) received nimodipine (10-20 mg t.i.d., according to body weight), for 12 weeks. After a 4-week wash-out period, the groups switched therapy for a further 12 weeks. 30 patients completed the trial and the number of dropouts was comparable in the 2 groups. The only side-effect during nimodipine treatment was mild abdominal discomfort (3 cases). The treatments were evaluated on the basis of frequency and duration of attacks. There was a significant reduction in both parameters during the first period of treatment. During the second period of treatment, nimodipine proved to have a significantly greater effect than the placebo with regard to frequency, whereas the response was similar with the placebo as regards duration of attacks. The latter parameter shows a significant decrease during the treatment periods, regardless of type of therapy. PMID- 2191939 TI - Effect of the structure of hospital payment on length of stay. AB - In response to rapidly rising costs, payers for health care services have made a number of changes in the way they reimburse hospitals for care. In this article we study the effect of different payment methods on the length of stay of Medicaid patients. We examine supply response by type of patient (medical, surgical, and psychiatric) and hospital ownership. We find that per case payment systems and negotiated contracts lead to significant decreases in the length of stay for all groups. Prospective per diem with limits in most cases leads to decreases in the length of stay. In general, we find that the supply response is stronger for psychiatric patients than for medical and surgical patients, and that publicly owned hospitals are more responsive to payment system incentives than are nonpublic hospitals. PMID- 2191940 TI - Aspirin and stroke prevention: how much? AB - Media attention concerning aspirin and the prevention of heart attack has been great, but there has been no similar attention to the subject of aspirin and stroke prevention. Clinical information is available in the literature concerning aspirin dosage and stroke prevention following transient ischemic attack (TIA). However, confusion still exists regarding appropriate dosing as well as the effectiveness of other antiplatelet agents. This review focuses on the mechanism of action of aspirin and cites the rationale provided by clinical trials for a recommendation of 1300 mg of aspirin per day as the sole orally administered antiplatelet agent. PMID- 2191941 TI - Meckel's diverticulum: report of two cases and review of the literature. AB - Meckel's diverticulum is considered the most common diverticulum of the small intestine. Of the various complications associated with this condition, intestinal obstruction is one of the most common. Rapid diagnosis and treatment are essential. Resection of the obstructing element is the treatment of choice. The authors report on their recent experience with two patients with Meckel's diverticulum, both of whom had intestinal obstruction as the presenting complication. The authors discuss the etiology and various complications of Meckel's diverticulum and present information on the frequency of associated mortality and morbidity. PMID- 2191942 TI - The European teachers of Dr. Frieda Fromm-Reichmann. PMID- 2191943 TI - Psychoanalysis and psychosis: the contribution of Edward Kempf. PMID- 2191944 TI - Abnormal venous connection between the left upper pulmonary vein and the left brachiocephalic vein, associated with rheumatic combined valvular heart disease. AB - A case of partial anomalous pulmonary venous return (PAPVR) associated with mitral stenosis and aortic regurgitation is described. The diagnostic clue was radiocardiography using radioiodide serum albumin (RISA), our routine procedure before cardiac catheterization. The abnormal vessel connected with both the left upper pulmonary vein (PV) and the left brachiocephalic vein, without a stenotic lesion. Aortic valve replacement, open mitral commissurotomy, and simple ligation of the anomalous vein were successfully performed. PMID- 2191945 TI - The genes of hepatic glucose metabolism. PMID- 2191946 TI - Crystallization and preliminary x-ray investigation of colicin E3 in complex with its immunity protein. AB - Crystals of the colicin E3-immunity protein complex have been grown from solutions of citrate at pH 5.6. The crystals are monoclinic, space group P2(1), with unit cell dimensions a = 67.71, b = 196.67, c = 85.58 A, and beta = 113.67 degrees. The crystals diffract to 3-A resolution and are stable in the x-ray beam for at least a day. Although the stoichiometry of the complex in solution is 1:1 there are two, three, or four such binary complex molecules in the asymmetric unit. PMID- 2191947 TI - N-acetylcolchinol O-methyl ether and thiocolchicine, potent analogs of colchicine modified in the C ring. Evaluation of the mechanistic basis for their enhanced biological properties. AB - Two colchicine analogs with modifications only in the C ring are better inhibitors than colchicine of cell growth and tubulin polymerization. Radiolabeled thiocolchicine (with a thiomethyl instead of a methoxy group at position C-10) and N-acetylcolchinol O-methyl ether (NCME) (with a methoxy substituted benzenoid instead of the methoxy-substituted tropone C ring) were prepared for comparison with colchicine. Scatchard analysis indicated a single binding site with KD values of 1.0-2.3 microM. Thiocolchicine was bound 2-4 times as rapidly as colchicine, but the activation energies of the reactions were nearly identical (18 kcal/mol for colchicine, 20 kcal/mol for thiocolchicine). NCME bound to tubulin in a biphasic reaction. The faster phase was 60 times as fast as colchicine binding at 37 degrees C, and a substantial reaction occurred at 0 degrees C. The rate of the faster phase of NCME binding changed relatively little as a function of temperature, so the activation energy was only 7.0 kcal/mol. Dissociation reactions were also evaluated, and at 37 degrees C the half-lives of the tubulin-drug complexes were 11 min for NCME, 24 h for thiocolchicine, and 27 h for colchicine. Relative dissociation rates as a function of temperature varied little among the drug complexes. Activation energies for the dissociation reactions were 30 kcal/mol for thiocolchicine, 27 kcal/mol for NCME, and 24 kcal/mol for colchicine. Comparison of the activation energies of association and dissociation yielded free energies for the binding reactions of -20 kcal/mol for NCME, -10 kcal/mol for thiocolchicine, and -6 kcal/mol for colchicine. The greater effectiveness of NCME and thiocolchicine as compared with colchicine in biological assays probably derives from their more rapid binding to tubulin and the lower free energies of their binding reactions. PMID- 2191948 TI - Cloning and characterization of the iron-sulfur subunit gene of succinate dehydrogenase from Saccharomyces cerevisiae. AB - We describe the cloning and characterization of the complete gene for the iron sulfur protein subunit of succinate dehydrogenase (EC 1.3.99.1) from Saccharomyces cerevisiae. The promoter and coding sequence have been cloned into an Escherichia coli-yeast shuttle vector. The cloned gene complements the defect in a succinate dehydrogenase-deficient yeast mutant isolated by us, and gene expression is fully responsive to induction by glucose deprivation, indicating that the promoter is intact. PMID- 2191949 TI - Nucleotide sequence of the fadA gene. Primary structure of 3-ketoacyl-coenzyme A thiolase from Escherichia coli and the structural organization of the fadAB operon. AB - The DNA insert of plasmid pK52 contains the fadAB operon coding for the Escherichia coli fatty acid oxidation complex. Studies on the operon's structure and organization revealed that the initiator codon (ATG) of the structural gene for 3-ketoacyl-CoA thiolase, the fadA gene, is located 109 nucleotides 3' to the stop codon (TGA) of the fadB gene that encodes the alpha-subunit, a multifunctional polypeptide. The direction of transcription of this operon is thus from fadB to fadA. The orientation of the fadA and fadB genes is the reverse of what had been published previously. The structural gene for thiolase is 1,164 nucleotides long and starts six nucleotides downstream from a Shine-Dalgarno sequence. 109 nucleotides of 5'-noncoding and 321 nucleotides of 3'-noncoding regions are also reported. The 3-ketoacyl-CoA thiolase beta-subunit is composed of 388 residues and has a calculated Mr of 40,889. The alpha- and beta-subunits were separated by gel filtration in formic acid, and the sequence of the amino terminal 10 amino acids of the beta-subunit coincided with that deduced from the nucleotide sequence data. Sequence comparisons suggest that Cys-91 of the E. coli enzyme is the active-site cysteine residue and that the consensus sequence of the active sites of 3-ketoacyl-CoA thiolases is Asn-Arg-X1-Cys-X2-Ser-X3-X4-Gln. Although the quaternary structure of E. coli 3-ketoacyl-CoA thiolase is different from that of other thiolases, the sequence is homologous to rat and human peroxisomal and rat mitochondrial 3-ketoacyl-CoA thiolases, to the extent of 42, 41, and 37%, identity, respectively. An evolutionary tree of thiolases was constructed; it suggests that the genes of E. coli and peroxisomal 3-ketoacyl-CoA thiolases diverged after the appearance of eukaryotic cells. PMID- 2191950 TI - Functional analysis of the endothelin-1 gene promoter. Evidence for an endothelial cell-specific cis-acting sequence. AB - Endothelin-1 (ET-1) is a peptide synthesized by endothelial cells both in culture and in vivo. ET-1 induces contraction of smooth muscle cells and stimulates growth in a variety of mesenchymal cell types. We have previously characterized the genomic organization of the ET-1 gene and described its chromosomal localization and promoter region sequence. In this report, we describe the use of fusion plasmids containing ET-1 5'-flanking sequence and the chloramphenicol acetyltransferase gene to identify cis-acting sequences that direct transcription of the ET-1 gene. When transfected into bovine aortic endothelial cells, constructs containing 143 base pairs of ET-1 5'-flanking sequence allowed maximal transcription, whereas constructs containing 129 base pairs of sequence had 40 fold lower rates of transcription. A synthetic DNA fragment encoding the region delineated by these deletion mutants was found to have a positive effect on transcription when placed in either orientation upstream of short inactive ET-1 promoter constructs. However, this increase in transcription was noted only when a second region containing an AP1 consensus sequence was also included in the constructs. In experiments with a heterologous promoter and a 119-base pair DNA fragment containing these two functional regions, this 119-base pair sequence acted in a positive and endothelial cell-specific fashion. Taken together, these data localize cis-acting sequences important in determining the rate and tissue specificity of ET-1 gene transcription and should allow the study of protein-DNA interactions which mediate transcription of this gene in endothelial cells. PMID- 2191951 TI - Alkyl hydroperoxide reductase from Salmonella typhimurium. Sequence and homology to thioredoxin reductase and other flavoprotein disulfide oxidoreductases. AB - The DNA sequence of the Salmonella typhimurium ahp locus was determined. The locus was found to contain two genes that encode the two proteins (C22 and F52a) that comprise the S. typhimurium alkyl hydroperoxide reductase activity. The predicted sequence of the F52a protein component of the alkyl hydroperoxide reductase was found to be highly homologous to the Escherichia coli thioredoxin reductase protein (34% identity with many conservative substitutions). The homology was found to be particularly striking in the region containing the redox active cysteines of the thioredoxin reductase molecule, and among the identities were the redox-active cysteines themselves. Aside from the strong similarity to thioredoxin reductase, overall homology between the F52a protein and other flavoprotein disulfide oxidoreductases such as glutathione reductase, dihydrolipoamide dehydrogenase, and mercuric reductase was found to be rather limited, and the conserved active site segment common to the three proteins was not observed within the F52a protein. However, three short segments that have been implicated in FAD and NAD binding were found to be conserved between the F52a protein and the other disulfide reductases. These results suggest that the alkyl hydroperoxide reductase is the second known member of a class of disulfide oxidoreductases which was represented previously by thioredoxin reductase alone; they also allow the putative assignment of several functional domains. PMID- 2191952 TI - The basement membrane glycoprotein entactin promotes cell attachment and binds calcium ions. AB - Mouse entactin derived from the extracellular matrix of M1536-B3 cells and from insect cells infected with a recombinant virus containing entactin sequences were shown to promote the attachment of mouse mammary tumor, human melanoma, and other cells. The cell attachment was inhibited by antibodies against mouse entactin but not by anti-fibronectin or anti-laminin antibodies. On a weight basis entactin was as effective as laminin in promoting the attachment of mouse mammary tumor cells. The attachment of cells to entactin was in part mediated by the integrin recognition RGD peptide sequence. This was demonstrated by the cell attachment properties of peptides derived from entactin which contained this sequence. Furthermore, the peptide RGDS could inhibit the attachment of mouse mammary tumor cells to entactin to approximately 60% of control. It is suggested that additional cell recognition sequences may be present in entactin. The direct binding of calcium ions to entactin was observed. It is probable that the binding sites reside in peptide sequences located toward the NH2 terminus region of entactin. This conclusion was supported by the demonstration that synthetic peptides, containing potential calcium binding sequences derived from entactin, bound calcium. In addition, a recombinant peptide containing the amino-terminal 330 amino acids of entactin also bound calcium ions. The significance of these properties of entactin is discussed. PMID- 2191953 TI - Differential stimulation of phosphorylation of initiation factors eIF-4F, eIF-4B, eIF-3, and ribosomal protein S6 by insulin and phorbol esters. AB - Exposure of quiescent, serum-starved 3T3-L1 cells to insulin promotes phosphorylation of initiation factors eIF-4F, eIF-4B, and eIF-3 p120, as well as ribosomal protein S6. Phosphorylation of both the p25 and p220 subunits of eIF-4F is stimulated typically by 2.5-5-fold, with a 2-4-fold increase in phosphorylation of eIF-4B and eIF-3 p120. Optimal stimulation is observed by 10( 9) M insulin. A similar pattern of stimulation is seen upon treatment of 3T3-L1 cells with 1 x 10(-6) M phorbol 12-myristate 13-acetate (PMA). Two-dimensional phosphopeptide mapping of p25, isolated from quiescent, insulin- or PMA stimulated cells, results in a single tryptic phosphopeptide, indicating a single phosphorylation site identical to that obtained with protein kinase C. A more complex phosphopeptide map is observed with the p220 subunit. Following PMA stimulation of 3T3-L1 cells, phosphopeptide mapping of p220 results in a pattern similar to that observed in vitro with Ca2+/phospholipid-dependent protein kinase (protein kinase C). Following insulin stimulation, mapping of p220 results in the appearance of novel peptides. Upon prolonged exposure to PMA, the cells are no longer responsive to this mitogen and no stimulation of phosphorylation of eIF 4F, eIF-4b, eIF-3 p120, or S6 via a protein kinase C-dependent mechanism is observed. Addition of insulin to these down-regulated cells leads to stimulation of phosphorylation of eIF-4F p220, ribosomal protein S6, and to a lesser extent, eIF-4B; little or no stimulation of phosphorylation of eIF-4F p25 and eIF-3 p120 is observed. Thus, eIF-4F p220, eIF-4B and ribosomal protein S6 are phosphorylated via PMA-dependent and insulin-dependent pathways, whereas phosphorylation of eIF-4F p25 and eIF-3 p120 is stimulated only upon activation of protein kinase C. Phosphopeptide maps of eIF-4F p220 and ribosomal protein S6 suggest that protease-activated kinase II is one of the protein kinases involved in the insulin-stimulated response in protein kinase C-depleted cells. PMID- 2191955 TI - Covalent association of the traI gene product of plasmid RP4 with the 5'-terminal nucleotide at the relaxation nick site. AB - Formation of relaxosomes is the first step in the initiation of transfer DNA replication during bacterial conjugation. This nucleoprotein complex contains all components capable of introducing a site- and strand-specific nick at a cognate transfer origin (oriT) on supercoiled plasmid DNA, thus providing the substrate for generation of the strand to be transferred. Characterization of the terminal nucleotides at the oriT nick site revealed that relaxation occurs by hydrolysis of a single phosphodiester bond between a 2'-deoxyguanosyl and a 2'-deoxycytidyl residue. The relaxation nick site and a 19-base pair invert repeat sequence that is recognized by asymmetric binding of the RP4 TraJ protein are interspaced by 8 base pairs. The nicking reaction results in covalent attachment of the RP4 TraI protein to the 5'-terminal 2'-deoxycytidyl residue of the cleaved strand. The arrangement of the TraJ binding site and the relaxation nick site on the same side of the DNA double helix suggests that protein-protein interactions between TraJ and TraI are a prerequisite for oriT specific nicking. In accordance with the current model of transfer DNA replication, the 3' end remains accessible for primer extension by DNA polymerase I, enabling replacement strand synthesis in the donor cell by a rolling circle-type mechanism. PMID- 2191954 TI - Molecular cloning of a cDNA for rat hepatic glutaminase. Sequence similarity to kidney-type glutaminase. AB - Mammalian liver possesses a unique isozyme of phosphate-activated glutaminase which plays an important role in the regulation of glutamine catabolism. Antibodies to hepatic glutaminase were used to screen a lambda gt11 rat liver cDNA library. One cDNA to hepatic glutaminase was identified. Changes in the relative abundance of hepatic glutaminase mRNA were determined by hybridization to this cDNA. The mRNA is found only in liver; it is not present prior to birth but its abundance increases dramatically at birth. The abundance of the mRNA is increased approximately 4-fold in diabetes. The sequence of the cDNA was compared to that recently published for kidney (brain)-type glutaminase (Banner, C., Hwang, J.-J., Shapiro, R.A., Wenthold, R.J., Nakatani, Y., Lampel, K.A., Thomas, J.W., Huie, D., and Curthoys, N.P. (1988) Mol. Brain Res. 3, 247-254). When the predicted amino acid sequences were compared a region of 123 amino acids with greater than 80% identity was found. The presence of scattered amino acid substitutions within stretches of identical amino acids suggests that the glutaminase isozymes are encoded by separate genes. This is the first demonstration of any similarity between the two glutaminases at the molecular level. PMID- 2191956 TI - Probing the role of arginines and histidines in the catalytic function and activation of yeast 3-phosphoglycerate kinase by site-directed mutagenesis. AB - A cluster of conserved histidines and arginines (His-62, His-167, Arg-21, Arg-38, and Arg-168) in 3-phosphoglycerate kinase (PGK) has been implicated as possibly involved in the binding of 3-phosphoglycerate (3-PG) and/or stabilization of the negatively charged transition state. The role of these residues in the catalytic function of yeast PGK and in the substrate- and sulfate-dependent activation was investigated by site-directed mutagenesis. The following substitutions, R21A, R21Q, H62Q, H167S, and R168Q, produced functional enzymes. In contrast, the R38A and R38Q mutations resulted in a complete loss of catalytic activity. These results demonstrate that of the basic residues studied, only arginine 38 is essential for the catalytic function of PGK. A moderate decrease in the catalytic efficiency as the result of the R21A, H167S, and R168Q mutations and an increased catalytic efficiency of the H62Q mutant rule out a possible role of a positive charge at these positions in the mechanism of phosphoryl transfer reaction. In contrast to the wild type PGK and the H62Q mutant, both of which are activated at low and inhibited at high sulfate concentration, the H167S, R168Q, and R21A mutants exhibited a progressive inhibition with increased concentration of sulfate. The activation observed at high concentration of either ATP or 3-PG as a variable substrate in the steady-state kinetics of wild type PGK was abolished as the result of the latter three mutations. The results of this work support the hypothesis that PGK has two binding sites for anionic ligands, the catalytic and regulatory sites for each substrate and the activatory and inhibitory sites for sulfate, and suggest that arginine 21, arginine 168, and histidine 167 are located in the activatory anion binding site, common for sulfate, 3-PG, and ATP. The increased Km values for both substrates and decreased specific activities of the mutants suggest that this regulatory site is close to the catalytic site. PMID- 2191957 TI - Role of leader peptide synthesis in repZ gene expression of the ColIb-P9 plasmid. AB - The frequency of replication initiation of the ColIb-P9 plasmid depends on the level of repZ expression, which has been shown to be negatively regulated by inc RNA, the approximately 70-base-long product of the inc gene. To further understand the regulatory mechanism of repZ gene expression, we isolated mutants defective in ColIb-P9 replication using a lambda:ColIb-P9 hybrid phage. Among six mutants isolated, one amber mutant, rep57, failed to synthesize the RepZ protein. The mutation occurred in the repZ leader sequence that encodes a 29-amino-acid reading frame, designated as repY. We also isolated mutants that suppressed the rep57 phenotype. These mutations were single base insertions between the repY initiation codon and the rep57 mutation site and resulted not only in a frame shift of repY but also in the formation of repY-repZ fusions without changing the amino acid sequence of RepZ. Thus, repY is not directly involved in the replication reaction but rather functions as a positive regulator for repZ expression. We propose that repZ expression is coupled with repY translation, which acts to disrupt a secondary structure sequestering the repZ translation initiation signal. The positive and negative regulations of repZ expression were discussed. The other mutants were mapped in repZ, confirming that repZ is essential for ColIb-P9 replication. PMID- 2191958 TI - Reactivity of alpha 1-antitrypsin mutants against proteolytic enzymes of the kallikrein-kinin, complement, and fibrinolytic systems. AB - Increased extracellular proteolysis because of unregulated activation of blood coagulation, complement, and fibrinolysis is observed in thrombosis, shock, and inflammation. In the present study, we have examined whether the plasma kallikrein-kinin system, the classical pathway of complement, and the fibrinolytic system could be inhibited by alpha 1-antitrypsin reactive site mutants. Wild-type alpha 1-antitrypsin contains a Met residue at P1 (position 358), the central position of the reactive center. It did not inhibit plasma kallikrein, beta-factor XIIa, plasmin, tissue-type plasminogen activator (t-PA), or urokinase. In contrast, these serine proteases were inhibited by alpha 1 antitrypsin Arg358. For the inhibition of C1s, a double mutant having Arg358 and a Pro----Ala mutation at P2 (position 357) was required. This double modification was made because C1-inhibitor, the natural inhibitor of C1s, has Arg and Ala residues at positions P1 and P2. Plasminogen activator inhibitor 1, the natural inhibitor of t-PA, also has Arg and Ala residues at positions P1 and P2. In a purified system, alpha 1-antitrypsin Ala357-Arg358 was 150-fold less efficient against C1s than C1-inhibitor and 27,000-fold less efficient against t-PA than plasminogen activator inhibitor-1. In plasma, 2.3 microM alpha 1-antitrypsin Ala357-Arg358 reduced by 65% the formation of a complex between kallikrein and C1 inhibitor following activation of the intrinsic pathway of blood coagulation by kaolin. Furthermore, after supplementation by 2.0 microM alpha 1-antitrypsin Ala357-Arg358, zymographic analysis showed that the majority of the free t-PA of normal plasma formed a bimolecular complex with the double mutant. In contrast, 3.4 microM alpha 1-antitrypsin Ala357-Arg358 did not prevent the activation of the classical pathway of complement observed when normal serum is supplemented with anti-C1-inhibitor F(ab')2 fragment. These results demonstrate that alpha 1 antitrypsin Ala357-Arg358 has therapeutic potential for disorders with unregulated activation of the intrinsic pathway of blood coagulation and the fibrinolytic system; however, the double mutant is not an efficient inhibitor for the classical pathway of complement. PMID- 2191959 TI - Timing of operative treatment of fractures in patients who have multiple injuries. PMID- 2191960 TI - The treatment of burns: an historical perspective with emphasis on the hand. AB - Since the use of fire became part of life, mankind has sought remedies to treat burns. The upper extremity, due to its frequency of exposure as the foremost organ in the everyday exploration of the environment and in manipulative and social interactions, is often involved. This article discusses the history of burn treatment. PMID- 2191961 TI - Experience with upper extremity burns. The Mount Vernon experience. AB - History and clinical examination remain the mainstay in assessing burn depth. There is no satisfactory objective test for burn depth. Silicone oil in loose bags is the dressing of choice for the conservative management of superficial burns. Deep dermal burns of the dorsum of the hand should be shaved and grafted within the first 5 days. Full-thickness burns of the dorsum without exposure of deep structures should be excised and grafted within the first 5 days. K-wires may be used to stabilize metacarpophalangeal and PIP joints to prevent secondary deformity while grafts heal, but should not be left longer than 6 weeks. Flaps used to repair full-thickness burns with exposure of deep structures should be planned to permit elevation and movement. Primary reconstruction of extensor mechanisms should be performed at the time of flap cover. PMID- 2191962 TI - Primary tangential excision for hand burns. AB - The article describes the correct technique of primary tangential excision in deep dermal and third-degree hand burns. The operation performed under tourniquet facilitates the preservation of viable tissue, which is of utmost importance in hand burns. The therapeutic results depend on the extent of destroyed tissue. Primary tangential excision prevents fibrosis due to prolonged infection and impaired circulation, thus creating much more favorable conditions for reconstruction and rehabilitation. PMID- 2191963 TI - Acute management of pediatric hand burns. AB - The pattern of injury seen in pediatric hand burns differs from adults because scald burns are most common. Many of these are difficult to assess at initial presentation. In addition, children develop less stiffness in response to immobilization. For these reasons, we have developed a conservative, expectant approach for treating most pediatric hand burns. Meticulous wound care, positioning, splinting, and exercise are required to safely accomplish the goals of rapid healing with minimal loss of function. These regimens are adapted specifically to suit the age of the child and are applied by the burn team. Normal hand function can be obtained in the majority of cases. PMID- 2191964 TI - Skin substitutes in upper extremity burns. AB - Four techniques for permanent skin replacement with skin substitutes are described. A claim of superiority to conventional skin grafting on upper extremity and hand burns is not made, but some clinical observations and histologic evidence of different healing characteristics are shown. The composite grafts described appear to effectively replace the bilayered structure of skin and seem to have good subjective resistance to shear forces. If the skin replacement is durable and heals with less scarring than conventional skin grafts, the inexorable course to stiffness and contracture may be altered. Further basic science and clinical investigation may provide us with a better way of managing these difficult problems. PMID- 2191965 TI - Evolving clinical and scientific concepts of upper extremity electrical trauma. AB - In conclusion, the pathogenesis of electrical injury is more complex than previously thought. Cellular damage occurs both by heating and electroporation. The relative contributions of heat and electroporation depend on the duration of electric current passage, the orientation of the cells, their location, and other factors. If the contact is brief, nonthermal mechanisms of cell damage may be most important. If the contact is much longer, heat damage will be most destructive. The characteristic time before heat damage predominates is probably a function of the electrical field strength in the tissue. If heat damage predominates, the injury may not be limited just to the plasma membrane but to other cell membranes as well. This is unlikely to be reversible. These parameters should also determine the pattern of injury. Damage by Joule heating is not known to be dependent on cell size, whereas larger cells are more vulnerable to membrane breakdown by electroporation. Cells do survive transient plasma membrane rupture under appropriate circumstances. Thus, if electroporation is the mechanism of damage, injured tissue may be salvageable; the challenge is to identify a technique that promptly reseals the damaged membranes. Current therapy requires a fully staffed and equipped intensive care unit, available operating suites, and the full range of available medical specialists. Major teaching hospitals are usually the prime candidates for operating an electric trauma unit. After initial resuscitation, efforts should be directed primarily toward preventing additional tissue loss mediated through a compartment syndrome. Renal and cardiac failure resulting from the release of intracellular muscle contents into the circulation must be prevented. Attention can then be directed toward maximizing tissue salvage and preventing late skeletal and neuromuscular complications. Finally, complex reconstructive procedures are needed to optimize the functional value of the remaining tissue. The eventual reconstructive goals should be kept in mind throughout the acute care of the patient. PMID- 2191966 TI - Chemical burns of the upper extremity. AB - Chemical burns are frequently encountered by the hand surgeon. Although operative therapy is not usually necessary, prompt accurate diagnosis, appropriate care, and close follow-up are required. Generalized treatment principles as well as specific therapies are discussed. PMID- 2191967 TI - Rehabilitation of the burned hand. AB - This paper presents a comprehensive overview of the rehabilitation and management of hand burns. The therapist, as an integral member of the burn team, significantly contributes to the successful outcome of this treatment. PMID- 2191968 TI - Management of the burned hand. 1970. PMID- 2191969 TI - Primary excision and prompt grafting as routine therapy for the treatment of thermal burns in children. 1976. PMID- 2191970 TI - Secondary repair of burned hands. 1981. PMID- 2191971 TI - Aesthetic aspects of hand surgery. Microsurgical approach with multiple free tissue transfers. 1981. PMID- 2191972 TI - [Excision of an intracardiac metastasis under chemotherapy]. AB - An intracardiac malignant lesion was found in a 28-year old male patient following orchidectomy for an advanced germinal tumour of the testicle. Although the patient is under chemotherapy, the neoplastic thrombus will be removed by surgery. Heart metastases are uncommon. When they do occur, they are usually secondary to locoregional extension and limited to the pericardium or myocardium. Endocardial or intracavitary lesions are rare, but can, in certain cases, be removed by surgery. PMID- 2191973 TI - [Malignant melanoma of the uterine cervix]. PMID- 2191974 TI - Significance of inguinal folds for diagnosis of congenital dislocation of the hip in infants aged three to four months. AB - We evaluated the usefulness of the appearance of asymmetrical inguinal folds in the frog leg position as a screening indicator for congenital dislocation of the hip (CDH) in the hope that we might be able to decrease the frequency of radiographic examinations of 3-4-month-old infants. Abnormal inguinal folds were observed in 499 (23.8%) of the 2,111 patients examined at the Asahikawa Health Center, and these 499 included all patients with complete dislocation or subluxation. Abnormal inguinal folds were also present in all 29 previously untreated patients with complete dislocation and in 11 with subluxation seen in our department. Because limited passive hip abduction is less sensitive than abnormal inguinal folds, we recommend inguinal fold assessment as a useful adjunct to other screening methods for CDH in 3-4-month-old infants. PMID- 2191975 TI - Studies on root enamel (2). Enamel pearls. A review of their morphology, localization, nomenclature, occurrence, classification, histogenesis and incidence. AB - Enamel pearls are one of a number of different enamel structures that can be found on the roots of deciduous and permanent teeth. They have a distinct predilection for the furcation areas of molar teeth, particularly the maxillary third and second molars. They can consist primarily of enamel, but in most instances, a core of dentin is contained within them. On rare occasions, even pulpal tissues can be found. Enamel pearls usually occur singularly, but up to 4 enamel pearls have been observed on the same tooth. Depending on the study, enamel pearls on permanent molar teeth have an incidence rate of between 1.1% 9.7% with distinct differences among racial and national groups. The incidence of enamel pearls increases greatly in histological studies, suggesting that they are often obscured by a covering of cementum. PMID- 2191976 TI - Effects of cavitational activity on the root surface of teeth during ultrasonic scaling. AB - It is recognised that roughness of the root surface will occur during ultrasonic scaling and this has been attributed to the vibrating scaling tip. Although the presence of cavitational activity and acoustic microstreaming forces have been described their effects on the root surface have not been fully evaluated. Utilising an in vitro system of polished gold, it was possible to demonstrate an indentation produced by the scaling tip. However cavitational activity around the tip within the water supply appeared to produce an area of erosion (0.66 +/- 0.3 mm2, 1 SD, n = 10), and the surface appeared pitted. A scanning electron microscope study (SEM) of root surfaces following ultrasonic scaling showed similar areas of erosion. A replica technique was utilised so that control and experimental root surfaces could be observed. Cavitational activity and acoustic microstreaming resulted in a superficial removal of root surface constituents, and this area of removal was measured as 0.7 +/- 0.3 mm2 (1 SD, n = 10), which was not significantly different from that area observed with the gold surface system (p greater than 0.1). It may be concluded that cavitational activity within the cooling water supply of the ultrasonic scaler results in a superficial removal of root surface constituents. PMID- 2191977 TI - The use of autologous fibronectin in the surgical repair of through-and-through furcation lesions in man. A pilot study. AB - 4 subjects with bilateral through-and-through mandibular furcation lesions were assessed for the healing response in terms of attachment gain following surgical debridement, root planing, citric acid demineralisation and topical application of autologous fibronectin. The results were compared with sham-operated and saline-treated contra-lateral sites. There was no significant difference in the attachment gain at sites treated with autologous fibronectin and citric acid compared with sites treated with citric acid alone. PMID- 2191978 TI - Influence of captopril on urinary excretion of furosemide in hypertensive subjects. AB - Influence of captopril on urinary excretion of furosemide was examined in a placebo-controlled, crossover design. Furosemide (20 mg) was injected intravenously in eight hypertensive subjects with pretreatment with captopril (25 mg) or matching placebo. Urine samples for furosemide and sodium were collected during the following intervals: -60-0, 0-60, 60-120, and 120-180 minutes after furosemide. Blood samples for plasma renin activity (PRA) and angiotensin II (AII) were obtained, and blood pressure was measured at -60, 0, 60, 120, and 180 minutes after furosemide. No significant difference was observed in urinary excretion of furosemide, volume or sodium between these trials. Although PRA increased following furosemide with captopril, as predicted plasma AII did not increase. Blood pressure significantly decreased following the combined therapy, but not furosemide alone. These data indicate that the urinary excretion of furosemide and its subsequent diuretic effects are not influenced by captopril. PMID- 2191979 TI - Oxide adherence and porcelain bonding to titanium and Ti-6Al-4V alloy. AB - The bonding of an experimental low-fusing porcelain to titanium and Ti-6Al-4V was evaluated by an x-ray spectrometric technique that measures the area that remains covered with porcelain following a controlled deformation of the metallic substrate. Oxide adherence strength values for titanium and Ti-6Al-4V oxidized at 750 degrees and 1000 degrees C were measured in tension with use of high-strength adhesives. The effect of further oxidation that would occur during porcelain firing was evaluated via simulated porcelain firings without actual porcelain application. Interface cross-sections of the titanium-porcelain and Ti-6Al-4V porcelain bonds were examined in a scanning electron microscope (SEM). The porcelain was found to delaminate completely from the metal substrate, leaving less than 1% of the surface covered with porcelain. The oxide adherence of the specimens oxidized at 750 degrees C was good, but those oxidized at 1000 degrees C exhibited significantly lower oxide adherence (p = 0.001). The simulated porcelain-firing oxidation treatments also produced a significant decrease in oxide adherence (p = 0.004). The 750 degrees C oxidation treatments produced oxide films too thin to be visualized in the SEM, whereas the 1000 degrees C oxidation treatments produced oxide films approximately 1 micron thick. The lower oxide adherence of the 1-micron-thick oxide films is consistent with reports in the titanium literature of oxide delamination when the oxide film reaches 1 micron in thickness. PMID- 2191980 TI - Effect of pH on the growth and proteolytic activity of Porphyromonas gingivalis and Bacteroides intermedius. AB - The effect of pH on the growth and proteolytic activity of the type strain and fresh isolates of Porphyromonas gingivalis and Bacteroides intermedius was investigated. B. intermedius strains grew with and without glucose at a pH as low as 5.0. These bacteria grew almost as well as Streptococcus mutans at pH 5.0 and better than Actinomyces viscosus at pH 5.5 and 5.0. Some B. intermedius strains raised the culture pH when grown at a low pH without glucose. In contrast, P. gingivalis strains grew only at pH 6.5 to 7.0. The P. gingivalis strains had proteolytic activities against azocoll, azocasein, and azoalbumin, while the B. intermedius strains degraded azocasein and azoalbumin, but not azocoll. B. intermedius showed maximum proteolytic activity at pH 7.0, and high activity over a wide pH range. In contrast, the optimum pH of proteolytic activity in P. gingivalis was pH 7.5 to 8.0. The P. gingivalis activities were more sensitive than those of B. intermedius to low pH. The capacity of B. intermedius to degrade proteins to more readily metabolizable substrates at low pH might explain the growth of this bacterium in an acidic environment. These differences between B. intermedius and P. gingivalis could explain their capacity to survive at different sites in the oral cavity and indicate how B. intermedius might positively influence the growth of P. gingivalis in subgingival plaque. PMID- 2191981 TI - Facts and artefacts in research on human dental plaque fluid. AB - In 1966, Jenkins suggested that the plaque fluid environment was likely to have higher concentrations of extracellular solutes than was apparent from analyses of total plaque concentrations. Early work on plaque fluid confirmed this contention, but some artefact was also generated by the prolonged centrifugation used for separation. The solute concentrations in plaque fluid mostly exceed those in saliva or crevicular fluid. Thus, the environmental conditions are distinctly different from those based on the assumption that saliva readily permeates films of dental plaque. In contrast, the presence of serum proteins suggests a crevicular input to plaque fluid. These data suggest that exchange between dental plaque and its environment is apparently restricted. Diffusion rates measured in dental plaque by different methods do not agree on how restricted it is. However, measuring diffusion in plaque introduces artefacts in packing density, a major determinant of the diffusion rate. The conditions used for collection and analysis have been reported to produce artefactual changes in plaque fluid potassium, a predominantly intracellular ion. Measurements of predominantly extracellular ions, such as calcium, are no less prone to artefact, whether based on ion-selective electrodes or on total calcium. We have much to learn about the fluid environment of the teeth and about dynamic changes in plaque fluid composition and properties during perturbations. Such information can give insights into pathological processes such as tooth demineralization and dental caries, calculus formation, and gingival inflammation. PMID- 2191982 TI - Plaque fluid as a bacterial milieu. AB - Studies of the extracellular, free concentrations of substrates, growth factors, inhibitors, and end-products of metabolism to which the intact plaque microflora is exposed in situ can assist in the understanding of factors controlling plaque pathogenicity. Information is becoming increasingly available from analysis of fluid separated by centrifugation of plaques collected at various intervals after an intra-oral pulse of dietary or experimental substrate, or different procedures or treatments having cariostatic potential. Such analytical results give more information than those obtained by analysis of aqueous or other extracts, because they yield values of substrate concentration representing those occurring at the bacterial cell surface. The largest body of information concerns extracellular levels of acid end-products of sugar catabolism in relation to food quality or sequence, and of amino acids and other products of nitrogen metabolism, in relation to studies of the detailed metabolic events of the Stephan curve, and of the demineralizing effect of the plaque environment. Areas where little information is available and which merit further study include plaque clearance of salivary and other components with anti-caries activity (e.g., antibodies, enzymes, fluorides, cations, other antimicrobials, etc.), and substrate concentrations to determine gradients for diffusion into and out of plaque. PMID- 2191983 TI - An assessment of recent advances in the study of the chemistry and biochemistry of dental plaque fluid. AB - This paper discusses key points made during the symposium in the light of work carried out in other laboratories. It is emphasized that the unique importance of plaque fluid is that the net result of chemical changes induced by microbial activity is reflected in this medium, which is in intimate contact with the enamel surface, and that this medium is accessible to chemical and biochemical analyses. However, in order to assess the cariogenic potential of plaque, we must consider the properties of both whole plaque and plaque fluid together. Although it is apparent that results of plaque fluid composition are sensitive to both isolation and the storage procedures utilized, plaque fluid appears to be a distinct entity within the oral cavity. Technical advances have been made which allow for the determination of the activity of selected ions (hydrogen, calcium, phosphate, potassium, fluoride) in plaque fluid obtained from a single site within the mouth. It appears, however, that such data alone may be insufficient to define the cariogenic potential of plaque appropriately. Evidence is presented from which it can be concluded that, with use of pooled samples of plaque obtained from individuals with clear differences in caries experience, results on plaque and plaque fluid composition can be obtained which are consistent with noted differences in caries susceptibility. The importance of base production is also discussed, and it is noted that few studies have been carried out to elucidate the role of proteins found in plaque fluid. In conclusion, recent advances in the study of plaque fluid have provided new insights into the mechanism of caries formation which are also germane to the formation of dental calculi. PMID- 2191984 TI - Suture tensor. AB - The suture tensor is a simple stainless steel device that pulls the ends of a running subcuticular suture in opposite directions, maintaining the desired closure. The benefits of the use of this device may include minimization of train track and excisional scarification (via the enhanced maintenance of "tenting"), time savings, and flexibility and durability for the sporting or physically active patient. PMID- 2191986 TI - The literature of dermatologic surgery and oncology: 1970-present. PMID- 2191985 TI - ASDS 20th anniversary: the dermatologic surgeon: blueprint for a state society. PMID- 2191987 TI - Correlation of contractility and proliferative potential with the extent of differentiation in mouse fibroblastic cell lines cultured in collagen lattices. AB - Four types of fibroblastic cell lines at various stage of differentiation, which had been derived from syngeneic mice, were cultured in collagen lattices (reconstituted dermis model). Lattice contraction, growth in the lattice, and cell morphology were compared. The following cell lines were used: [I] precrisis cells within several subcultures derived from the skin of Balb/c mice, [II] an established normal cell line derived from syngeneic mice (Balb/3T3 clone A31), and [III] two transformed lines (Balb/3T12-3, 3T3-B-SV40) originating from [II]. The cells adopted a bipolar spindle form in the collagen lattice. Lattice contraction was the most marked with cell type [I] followed in order by [II] and [III]. Relative growth in the lattice occurred in the reverse order (III greater than II greater than I). These findings suggested a correlation between lattice contraction and growth in the lattice and also between the extent of differentiation and lattice contraction. PMID- 2191988 TI - Reproduction of the skin lesions of polymorphous light eruption: a case report and a review of the Japanese literature. AB - A case of polymorphous light eruption with plaque-type lesions is reported. A 55 year-old male had pruritic erythemas and plaques on the head, the face, the nape, the back of the hands, and the left loin within days following sun exposure. The patient's minimal erythema dose (MED) (60 mJ/cm2) of sunlamp irradiation for ultraviolet (UV) B was normal. Three once-daily exposures to 2 MED of UVB (Epstein's repeat phototest technique) produced pruritic papules with a similar microscopic appearance to that of the patient's skin lesion, indicating that the action spectrum causing the lesion seemed to be within the UVB waveband. PMID- 2191989 TI - Comparison between RAST and Pharmacia CAP system: a new automated specific IgE assay. AB - RAST represents the standard technique to titrate serum-specific IgE and was found to have a higher efficiency in the diagnosis of IgE-mediated allergy than other in vitro tests. Pharmacia CAP system (CAP) is a new solid-phase immunoassay, fully automated, used for the titration of specific IgE antibodies. Results are listed in kilounits per liter, equilibrated against the World Health Organization standard for IgE. RAST and CAP were compared in 106 unselected patients (6 to 59 years) characterized by a detailed clinical history and skin prick tests with standardized allergen extracts. IgE to cat, Dermatophagoides pteronyssinus, Alternaria, orchard grass, olive, and Parietaria pollen were tested; 470 tests were run. The specificity, sensitivity, and efficiency of both in vitro tests ranged from 85.5% to 100% except for olive pollen, in which the sensitivity of both in vitro tests was low (68.2% for the new test and 63.6% for RAST). Except for orchard-grass pollen, the sensitivity and specificity of CAP were better than that of RAST. There was a highly significant correlation between both tests (r range, between 0.864 to 0.987). CAP competes favorably with RAST and has the advantage of being automated and eliciting results in kilounits per liter. PMID- 2191990 TI - Comparison of the intensity and duration of effects of inhaled bitolterol and albuterol on airway caliber and airway responsiveness to histamine. AB - Inhaled beta-agonists can produce bronchodilatation and reduce airway hyperreactivity in patients with asthma. Using these two measures, we compared inhaled bitolterol (three puffs, 1110 micrograms), albuterol (two puffs, 180 micrograms), and placebo administered by metered-dose inhaler in a blinded, crossover study of 40 subjects with chronic asthma. On each study day, subjects underwent histamine challenges at 1 1/2 hours before, and 1/2, 2, 4, 6, and 8 hours after inhaling one of the three test-drug treatments. Both drugs produced significant bronchodilatation at 30 minutes through 4 hours and significant effects on airway reactivity at 30 minutes through 2 hours (p less than 0.05). Bitolterol also produced small but significant bronchodilator effects at 6 hours and effects on airway reactivity at 4 hours (p less than 0.05). Effects of bitolterol on airway reactivity diminished significantly more slowly than effects of albuterol in subjects with baseline provocative concentration causing a 20% fall in FEV1 greater than or equal to 1.0 mg/ml of histamine (half-life of biologic effect 1.37 versus 0.92 hours; p less than 0.05) but not in subjects with baseline provocative concentration causing a 20% fall in FEV1 less than or equal to 1.0 mg/ml (half-life of biologic effect of 1.01 versus 1.00 hours; p greater than 0.05). PMID- 2191991 TI - A double-blind study of the effectiveness of a high-efficiency particulate air (HEPA) filter in the treatment of patients with perennial allergic rhinitis and asthma. AB - This study was designed to assess the effectiveness of a high-efficiency particulate air (HEPA) filter in alleviating allergic respiratory symptoms. Thirty-two patients were studied who had symptomatic perennial rhinitis and/or asthma during the fall and winter months and had a positive skin test with house dust or house dust--mite extract. An ENVIRACAIRE room air cleaner was placed in the bedroom for 8 weeks. In a random manner, the active filter was used for 4 weeks and a blank filter for 4 weeks. There was an average 70% reduction in the particulate matter greater than or equal to 0.3 micron with the HEPA filter. In a double-blind design, results were assessed by analysis of the patients' symptom/medication scores and subjective evaluation. For the total study, there was no difference in the total symptom/medication scores or individual symptom scores during the placebo and active-filter periods. Analysis of the last 2 weeks of each filter period in which respiratory infection was absent demonstrated definite differences in total and individual symptoms, suggesting active-filter benefit. Patients' subjective responses also suggested benefit from the filter. The overall impression is that the HEPA filter can reduce allergic respiratory symptoms. PMID- 2191992 TI - Steroid dose sparing: pharmacodynamic responses to single versus divided doses of methylprednisolone in man. AB - Inhibitory drug interactions affecting the metabolism of methylprednisolone (MP) may produce either steroid sparing or adverse effects partly by increasing the exposure time to the steroid. This phenomenon can be mimicked by administering MP in divided doses. Two types of responses were compared after a single MP dose (40 mg bolus) and a divided regimen (20 mg bolus and a 5 mg bolus 8 hours later) in six healthy male volunteers. The suppression of basophils measured as whole blood histamine and plasma cortisol concentrations was assessed during 32 hours. The 37.5% reduction in dose produced a 23% overall decreased blood histamine response. A pharmacodynamic model for basophil cell distribution to and from an extravascular compartment describes the effects of MP after both regimens. A slower initial decline in blood histamine after the divided regimen may be related to incomplete suppression of basophil cell return to blood. The 50% inhibitory concentrations of MP of about 5 ng/ml were similar for both regimens. The decline and return of cortisol concentrations were similar between MP treatments with suppression continuing for 24 hours. The 50% inhibitory concentrations of MP values for adrenal suppression were about 1 ng/ml. Pharmacodynamic modeling is useful in quantitating corticosteroid responses and generally predicted the "dose-sparing" effects that were achieved by prolonging MP plasma concentrations. This study supports previous clinical observations that patients may require morning through evening exposure to MP to optimize efficacy while adrenal suppression is being minimized. PMID- 2191993 TI - The effect of an inhaled leukotriene antagonist, L-648,051, on early and late asthmatic reactions and subsequent increase in airway responsiveness in man. AB - We have investigated the protective effects of the inhaled cysteinyl leukotriene antagonist, L-648,051, on allergen-induced early asthmatic response (EAR) and late asthmatic response (LAR) and the subsequent changes in bronchial responsiveness to methacholine. Ten atopic men with asthma participated in a double-blind, crossover, placebo-controlled trial. All subjects had documented EAR and LAR to house dust-mite extract. Responsiveness to methacholine was measured the day before and the day after a standardized allergen-challenge test. L-648,051 was inhaled in two doses of 12 mg 20 minutes before and 3 hours after the allergen challenge. The response was obtained from FEV1 and flows from maximal (V40m) and partial (V40p) expiratory flow-volume curves. All subjects had an EAR and LAR during placebo therapy, but only a minority demonstrated an increase in methacholine responsiveness of more than one doubling dose. The ratio of V40m to V40p during methacholine challenge was higher than during both EAR and LAR (p less than 0.05). There was no difference between drug- and placebo-therapy periods in baseline function, EAR, LAR, ratio of V40m to V40p, and the allergen induced hyperresponsiveness (p greater than 0.1). These results indicate that an effective aerosolized leukotriene antagonist in man does not protect against allergen-induced airflow obstruction, despite the evidence of an inflammatory response to allergen challenge. This suggests that either the potency or duration of activity of L-648,051 is limited or that leukotrienes C4 and D4 do not play a causative role in human allergic asthma. PMID- 2191994 TI - Carrier detection of the X-linked primary immunodeficiency diseases using X chromosome inactivation analysis. AB - Carrier detection of three of the X-linked primary immunodeficiency diseases (X linked agammaglobulinemia, X-linked severe combined immunodeficiency disease, and the Wiskott-Aldrich syndrome) is possible by analyzing patterns of X-chromosome inactivation in those cells affected by the disorder. Normal women have balanced patterns of X-chromosome inactivation; that is, in a given population of cells, approximately half of their active X chromosomes are of paternal origin and half of their active X chromosomes are of maternal origin. In contrast, female carriers of these X-linked immunodeficiency disorders have an unbalanced pattern of X-chromosome inactivation in those cell lineages that are affected by the disorder; that is, all the active X chromosomes in affected cell lineages are the X chromosomes that carry the normal allele. Two techniques are available for X chromosome inactivation analysis. One technique depends on methylation differences between the active and inactive X chromosome, and the other technique uses somatic cell hybrids that selectively retain the active X chromosome. In either case, carrier detection can be performed in individuals from families in which only one member of the family has been affected, since neither of these methods depends on linkage analysis. PMID- 2191995 TI - Cold urticaria syndromes: historical background, diagnostic classification, clinical and laboratory characteristics, pathogenesis, and management. PMID- 2191996 TI - Optometry's role in reading disabilities: resolving the controversy. AB - Optometry's involvement in the management of reading disabilities is often misunderstood. This paper clarifies the confusion surrounding specific reading disabilities and optometric vision therapy in the management of them. Topics include a historical review of dyslexia, theories of brain function, and a neuroanatomical model, as well as operational definitions and behavioral characteristics of the types of dyslexia. Methods for direct diagnosis of coding deficits in specific reading disability (dyslexia) are discussed. This approach explains the beneficial role of optometric vision therapy in the management of patients with reading problems. PMID- 2191997 TI - Evaluation of the retinal nerve fiber layer in glaucoma. AB - The health of the optic nerve in glaucoma can be evaluated by examination of the retinal nerve fiber layer with red free illumination. Retinal nerve fiber layer defects have been shown in some studies to precede enlargement of optic cupping and visual field defects in glaucoma patients. Detection of glaucomatous damage at an earlier stage in the disease may prevent subsequent visual field loss. Retinal nerve fiber layer evaluation may give important information in the management and treatment of glaucoma patients. PMID- 2191998 TI - Legislation, litigation, health policy and optometry. AB - Significant changes in health policy have occurred during the past 25 years. Directed primarily by congressional legislation and judicial opinion, many of these changes have resulted from efforts to control costs, improve quality and increase access. Optometric parity, reimbursement reform, freedom of choice, mandated benefits, commercial speech, self-insurance, competition and peer review are some of the issues that surround many of the more recent attempts at change in the health care market. Optometry has been and will continue to be affected by changes in health policy, especially with regard to issues of cost, quality and access. PMID- 2191999 TI - The Histochemical Society: presentation of the Founder's Award and the Pioneers' Awards. PMID- 2192000 TI - Regulation of chromogranin B/secretogranin I and secretogranin II storage in GH4C1 cells. AB - GH4C1 cells are a rat pituitary tumor cell strain in which the level of cellular prolactin (PRL) and PRL-containing secretory granules can be regulated by hormone treatment. The chromogranins/secretogranins (Sg) are a family of secretory proteins which are widely distributed in the secretory granules of endocrine and neuronal cells. In the present study, we investigated in GH4C1 cell cultures the regulation of the cell content of the Sg by immunoblotting and the relationship between the storage of Sg I and Sg II and PRL by double immunocytochemistry. GH4C1 cells grown in the presence of gelded horse serum, a condition in which these cells contain a low level of secretory granules, contained low levels of PRL, Sg I, and Sg II. Treatment of GH4C1 cells with a combination of 17 beta estradiol, insulin, and epidermal growth factor for 3 days, known to induce a marked increase in the number of secretory granules, increased the cell contents of PRL, Sg I, and Sg II. To determine whether the induction of PRL was morphologically associated with that of the Sg, the distribution of PRL and the Sg was determined by double immunofluorescence microscopy. After hormone treatment, 54% of cells showed positive PRL immunoreactivity, fluorescence being extranuclear and consistent with staining of the Golgi zone and secretory granules. Forty-six percent of PRL-positive cells stained coincidently for Sg I, while 72% of the PRL cells were also reactive with anti-Sg II. To determine whether PRL storage was associated with storage of at least one of the Sg, cells were stained with anti-PRL and anti-Sg I and anti-Sg II together. Eighty-six percent of PRL cells stained for one or the other of the Sg. Therefore, PRL storage in GH4C1 cell cultures is closely but not completely associated with the storage of Sg I and/or II. PMID- 2192001 TI - Effect of basic fibroblast growth factor (bFGF) and insulin-like growth factors type I (IGF-I) and type II (IGF-II) on adult human keratinocyte growth and fibronectin secretion. AB - Effects of growth factors on keratinocyte migration and proliferation are of interest as an indication of their potential use in acceleration of wound re epithelialization. Various growth factors were examined for effects on normal adult human keratinocyte growth and fibronectin (Fn) secretion for cells cultured in serum-free medium. Accumulation of Fn in the medium of cells growth with H + I + EGF + BPE paralleled growth during the exponential phase and declined as the cells approached confluence. Cells maintained in low Ca++ (0.15 mM) post confluence and fed daily to prevent cornification continued to accumulate Fn in the medium, while those grown continuously in 1.2 mM Ca++ ceased Fn secretion at confluence. EGF, bFGF, and transforming growth factor-beta (TGF beta) stimulated keratinocyte Fn secretion in correlation with literature reports on the ability of these factors to stimulate the migration of these cells. In contrast, despite its marked effects on cell growth, BPE was found to consistently reduce the amount of Fn found in the medium when added to cultures containing either EGF or bFGF. Addition of BPE to cultures containing EGF or bFGF stimulated growth to the same extent, indicating that the effects of BPE on keratinocyte growth are not solely due to its content of bFGF. PMID- 2192002 TI - Studies of the relationship of the 230-kD and 180-kD bullous pemphigoid antigens. AB - In bullous pemphigoid (BP), autoantibodies from most patients recognize a high molecular weight 230-kD epidermal antigen (Ag) by immunoprecipitation. By Western immunoblotting, 50-70% of sera recognize the high molecular weight Ag, but 30-50% recognize a low molecular weight, 180-kD epidermal Ag. We examined the specificities of affinity-purified antibodies against these Ag. Antibodies specific for the 230- and 180-kD Ag were prepared by immunoaffinity against Ag immobilized on nitrocellulose and released by acid glycine. IgG eluted from the 230-kD Ag band retained its specific binding to the 230-kD Ag by immunoblotting, and bound to the epidermal basement membrane zone (BMZ) by indirect immunofluorescence (IF) and to hemidesmosomes by indirect immunoelectron microscopy (EM). IgG affinity purified by the 180-kD Ag band bound only the 180 kD Ag in immunoblotting, with no cross reaction to the 230-kD Ag, bound the epidermal BMZ by indirect IF, and also bound to hemidesmosomes in immuno-EM. IgG specific for the 230-kD Ag in immunoblotting immunoprecipitated only the 230-kD Ag, with no apparent precipitation of the 180-kD Ag. Surprisingly, IgG specific for the 180-kD Ag precipitated both the 180- and the 230-kD Ag in immunoprecipitation, and the 230-kD Ag band was much more intense than the 180-kD Ag band. This study shows that apparent cross-reactivity between these Ag by BP autoantibodies can only be detected in native conditions by immunoprecipitation, and cannot be demonstrated using denatured Ag in immunoblotting. The two proteins appear to be distinct Ag, closely associated in the epidermal hemidesmosome, but the exact relationship of these Ag to each other may not be clarified until complete structural data become available. PMID- 2192003 TI - Reactivity of sera from bullous pemphigoid patients on blotted epidermal extracts as compared to indirect immunofluorescence technique. PMID- 2192004 TI - The ability of recombinant murine granulocyte-macrophage colony-stimulating factor to protect neonatal rats from septic death due to Staphylococcus aureus. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) potentiates in vitro and in vivo production of granulocytes. Also, recombinant human GM-CSF in vitro enhances functional capabilities of human granulocytes. Recombinant murine (rm) GM-CSF was administered to neonatal rats in vivo to test its ability to protect from septic death due to Staphylococcus aureus. When rmGM-CSF was given intraperitoneally 6 h before a 90% lethal dose challenge of S. aureus, peak survival was observed at a dose of 30 pg/g (54% vs. 10% in animals administered saline; P less than .001). Blood cultures were positive for S. aureus in 26 of 32 saline-treated and in 5 of 31 rmGM-CSF-treated animals (P less than .001). Numbers of blood granulocytes were significantly increased 9 h after administration of rmGM-CSF (30 pg/g) but returned to control levels by 12 h. Neither neutrophil storage nor proliferative pools were affected. Thus, rmGM-CSF significantly improved survival when given prophylactically in a neonatal rat model of infection. PMID- 2192005 TI - The use of a specific DNA probe and polymerase chain reaction for the detection of Mycobacterium leprae. AB - A DNA probe encoding approximately 80% of the 18-kDa protein gene of Mycobacterium leprae was isolated and tested for specificity by assessing hybridization of the probe to genomic DNA from taxonomically related and unrelated DNA samples. The 360-base-pair (bp) probe was specific for M. leprae DNA and did not hybridize with genomic DNA from 18 species of bacteria nor with DNA from human, murine, and armadillo sources. Oligonucleotide primers were synthesized corresponding to the 5' and 3' ends of the 360-bp fragment to yield a fragment of similar size on amplification of M. leprae DNA by the polymerase chain reaction (PCR). A simple procedure for DNA extraction from M. leprae infected tissues was developed that provided suitable template DNA for amplification. The PCR test was specific for M. leprae DNA from human and murine sources and detected M. leprae DNA in biopsies from leprosy patients and from control and uninfected human skin biopsy preparations seeded with as few as 100 M. leprae. PMID- 2192006 TI - Seroprevalence of human T-lymphotropic virus type I or II in sexually transmitted disease clinic patients in the USA. AB - Serum specimens from patients attending sexually transmitted disease (STD) clinics in Denver and several southeastern US cities were tested for antibody to human T-lymphotropic virus type I or II (HTLV-I/II). In Denver, 8 (2.1%) of 384 patients with a history of intravenous (IV) drug use, versus none of 201 non-IV drug users, were HTLV-I/II seropositive. Only 2 (0.18%) of 1095 STD clinic patients from the southeastern USA had antibodies to HTLV-I/II. These data document a low prevalence of HTLV-I/II in STD clinic patients from the southeastern USA and confirm that IV drug use is an important risk factor for HTLV-I/II in the USA. PMID- 2192007 TI - Patterns of guanine nucleotide exchange reflecting disparate neutrophil activation pathways by opsonized and unopsonized Candida albicans hyphae. AB - Through guanosine triphosphate (GTP) regulatory proteins are crucial components in signal transduction by most soluble and opsonized particulate stimuli, previous data suggest that neutrophil (PMNL) activation by unopsonized hyphae differs. Most of the PMNL superoxide response evoked by unopsonized hyphae was independent of both Ca++ ions and pertussis toxin-sensitive guanine nucleotide regulatory proteins. To determine whether related regulatory proteins were involved in PMNL activation by unopsonized hyphae, separated PMNL plasma membranes were incubated with GTP and a poorly hydrolyzed, radiolabeled GTP analogue, 5'-guanylylimido-diphosphate, then stimulated. Particulate Candida albicans hyphae and soluble chemotactic peptide induced comparable guanine nucleotide release. In contrast, while unopsonized hyphae caused release, it was considerably delayed, though opsonization discernibly affected neither PMNL attachment nor spreading over hyphal surfaces. This paralleled earlier observations of other delayed responses by intact PMNL to unopsonized hyphae: phospholipase C activation, the rise in cytosolic free Ca++ ions, and actin polymerization. PMID- 2192008 TI - IgA antibodies for diagnosis of acute congenital and acquired toxoplasmosis. AB - An ELISA for IgA toxoplasma antibodies was positive in 12 pregnant women who seroconverted during gestation. Positive IgA titers were also noted in 10 individuals with biopsy-proven toxoplasmic lymphadenitis; the highest titers were noted in the first months following onset of clinical signs. Toxoplasma IgA antibodies were also demonstrable in 8 of 9 infants/fetuses with congenital toxoplasma infection. In some, IgM antibodies could not be demonstrated. Among 20 patients with AIDS and biopsy-proven toxoplasmic encephalitis, only 1 had IgA antibodies. None of 20 individuals with chronic toxoplasma infection had demonstrable IgA antibodies. Demonstration of IgA toxoplasma antibodies should be useful for diagnosis of recently acquired infection and for diagnosis of the infection in the fetus and newborn. PMID- 2192009 TI - Antibodies to phenolic glycolipid-1 of Mycobacterium leprae in urine of leprosy patients. PMID- 2192010 TI - T lymphocytes bearing the gamma delta T cell receptor in patients with acute Plasmodium falciparum malaria. PMID- 2192011 TI - A randomized trial of combination therapy with intralesional interferon alpha 2b and podophyllin versus podophyllin alone for the therapy of anogenital warts. AB - To determine the value of combining interferon with standard local therapy in the treatment of human papillomavirus infection, 97 patients with anogenital warts were randomized to a short course of either interferon plus podophyllin or podophyllin alone. Interferon alpha 2b (1.5 x 10(6) IU) was injected intralesionally and podophyllin resin applied topically to each of three warts once weekly for 3 weeks. Maximal responses occurred within 2 weeks of therapy, and overall there was complete clearance of treated warts in 67% of interferon and podophyllin versus 42% of podophyllin recipients (P less than .05, chi 2). Clearance rates were greater in women, patients with warts of less than or equal to 12 months' duration, and HIV-seronegative patients. Of patients with complete clearance, 67% of interferon and podophyllin and 65% of podophyllin recipients experienced recurrences. Thus, in short treatment courses of anogenital warts, intralesional interferon enhanced the effect of topical podophyllin, and trials of combination therapy using more intensive or prolonged regimens of interferon are warranted. PMID- 2192012 TI - Clonal relationships among classic enteropathogenic Escherichia coli (EPEC) belong to different O groups. AB - Fifty Escherichia coli strains belonging to nine classic EPEC (enteropathogenic E. coli) O:H serotypes from infantile diarrhea were examined for enzyme polymorphism and typed according to their multilocus genotypes. They were further examined for lipopolysaccharide (LPS) patterns by sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by silver staining, for localized adhesion to HEp2 cells, and for their outer membrane protein (OMP) pattern. A very close relationship was detected among electrophoretic type, O:H serotype, biotype, LPS type, and OMP pattern. Most likely these characteristic EPEC groups (all type I) each represented bacterial clones, and furthermore they could be grouped into two genetically closely related clusters. In each cluster the only phenotypic character that differed among strains was the O antigen, which might suggest that the genetic background for the LPS side chains can be transferred horizontally among EPEC strains. The results support the idea that O:H serotyping is useful for studies of epidemiologic linkages between cases of EPEC diarrhea. PMID- 2192013 TI - Diagnosis of human ehrlichiosis with the indirect fluorescent antibody test: kinetics and specificity. AB - Human ehrlichiosis, an acute febrile illness caused by Ehrlichia canis or a closely related rickettsial organism, was first identified in 1986. From 1986 through 1988, sera from 85 patients demonstrated a fourfold rise or fall in antibody titer to E. canis. Seven (22%) of 32 patients initially tested during the first week after onset of illness. 17 (68%) of 25 tested during the second week, and all 18 tested during the third week had titers that exceeded the minimum positive titer of greater than or equal to 80. Of the 85 confirmed ehrlichiosis patients, 31 (36.5%) also had indirect fluorescent antibody titers considered diagnostic of infection with Rickettsia rickettsii, Rickettsia typhi, or Coxiella burnetti, but in most these diagnoses were not supported by epidemiologic, clinical, or serologic evidence. These results emphasize that patients suspected of having a tick-borne infection should be tested for antibodies to E. canis as well as for those to other rickettsiae. PMID- 2192014 TI - Chronic treatment of rats with SCH-23390 or raclopride does not affect the concentrations of DARPP-32 or its mRNA in dopamine-innervated brain regions. AB - DARPP-32 (dopamine- and cyclic AMP-regulated phosphoprotein, Mr = 32,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) is a neuronal phosphoprotein that is enriched in neurons which possess dopamine D1 receptors, particularly striatonigral neurons. In rat brain slices, the phosphorylation state of DARPP-32 is regulated by dopamine, acting through the dopamine D1 receptor and the adenylyl cyclase system. This study reports that chronic blockade (21 days) of either dopamine D1 receptors by SCH-23390 or dopamine D2 receptors by raclopride does not affect the concentrations of DARPP 32 in specific rat brain regions (striatum, thalamus, hippocampus, frontal cerebral cortical pole). Northern blot analysis indicates that the steady-state level of DARPP-32 mRNA in striatum is also unchanged by these treatments. PMID- 2192015 TI - Interaction of strychnine-insensitive glycine binding with MK-801 binding in brain synaptic membranes. AB - Strychnine-insensitive [3H]glycine binding was detected in brain synaptic membranes treated with Triton X-100 using a filtration assay method. The binding was a time-dependent, inversely temperature-dependent, and reversible process with a relatively high affinity for the neuroactive amino acid. Scatchard analysis revealed that Triton treatment doubled both the affinity and density of the binding sites, which consisted of a single component. The binding was not only displaced by structurally-related amino acid such as D-serine and D-alanine, but also inhibited by some peptides containing glycine, including glycine methylester and N-methylglycine. These ligands invariably potentiated the binding of [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]- cyclohepten-5,10-imine ([3H]MK 801), a noncompetitive antagonist for the N-methyl-D-aspartate-sensitive subclass of the central excitatory amino acid receptors, in a concentration-dependent manner. Among various endogenous tryptophan metabolites, kynurenic acid significantly inhibited the strychnine-insensitive [3H]glycine binding. The Triton treatment did not affect the pharmacological profile of [3H]MK-801 binding sites. These results suggest that brain synaptic membranes treated with Triton X 100 are useful in evaluating the strychnine-insensitive and kynurenate-sensitive binding sites of glycine, which are functionally linked to N-methyl-D-aspartate- sensitive receptor channels. PMID- 2192016 TI - Basic fibroblast growth factor (bFGF) immunoreactivity is present in chromaffin granules. AB - Basic fibroblast growth factor (bFGF) has recently been isolated from bovine adrenal glands. Immunohistological data revealed its presence in both adrenal cortex and adrenal medulla. Using immuno-electronmicroscopy, we found that in medullary chromaffin cells bFGF-immunoreactivity is localized in the secretory granules. Immunoreactivity also was observed by electronmicroscopy in isolated granules. Western blot analysis revealed the presence of the typical 18-kDa bFGF and additional immunoreactive materials with molecular masses of approximately 24, 30, and 46 kDa in whole bovine adrenal, and in cortex and medulla. Similar results were obtained with proteins from bovine chromaffin granules, with the following two exceptions: the 46-kDa immunoreactivity was found to be highly enriched when compared with medulla or cortex, and the 18-kDa band could be detected with only an antiserum against a synthetic peptide comprising the 24 NH2 terminal amino acids of bFGF, and not with an antiserum against purified bovine pituitary bFGF. All fractions enriched for bFGF-immunoreactivity showed neurotrophic activity for chick ciliary ganglion neurons, which could be blocked by antibodies. These results demonstrate for the first time the localization and occurrence of bFGF in a cellular secretory organelle, and present further evidence for the existence of higher molecular weight immunoreactive forms of bFGF. PMID- 2192017 TI - Syringomyelia and syringobulbia following tuberculous meningitis. AB - Tuberculous meningitis may rarely be followed by the development of a syrinx even after apparently successful chemotherapy. There are only six previously reported cases of this unusual complication; these are reviewed. A case is described of syringomyelia which developed 1 year after TBM. One year later magnetic resonance imaging demonstrated not only the spontaneous resolution of the syringomyelia but also the appearance of a new cavity within the brain stem. This surprising sequence of events illustrates the need for extensive studies of the natural history of syrinxes of differing aetiologies. PMID- 2192018 TI - Comparison of therapeutic regimen of anticysticercal drugs for parenchymal brain cysticercosis. AB - The efficacy of different regimens of therapy for parenchymal brain cysticercosis either with praziquantel (PZQ) or with albendazole (ALB) was compared in 114 patients. Four schemes of treatment were used: PZQ 50 mg/kg per day for 15 days, PZQ 50 mg/kg per day for 8 days, ALB 15 mg/kg per day for 30 days, and ALB 15 mg/kg per day for 8 days. Three months after therapy, it was apparent that both PZQ and ALB were effective, as shown by the disappearance of cystic lesions in computed tomographic scans. Thirty-three control patients followed for a mean of 11 months had no spontaneous remission of lesions. When comparing PZQ with ALB, the latter was found to be more effective than the former for both the full and the short course of treatment: 85% vs 60% and 85% vs 48% disappearance of lesions, respectively (P less than 0.001). Comparison of the full vs the short course of PZQ showed that the short course had a further 12% reduction in drug effectiveness. In contrast, the length of ALB therapy could be shortened without lessening its efficacy. Based on these results, an 8-day course of ALB is recommended as treatment for parenchymal brain cysticercosis; a 15-day course of PZQ could be subsequently used in those patients who show only partial response to ALB. PMID- 2192019 TI - Biochemical and morphological differentiation of acetylcholinesterase-positive efferent fibers in the mouse cochlea. AB - We have compared the biochemical expression of cholinergic enzymes with the morphological differentiation of efferent nerve fibers and endings in the cochlea of the postnatally developing mouse. Choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) are present in the newborn cochlea at specific activities 63% and 25%, respectively, of their mature levels. The relative increases in ChAT, in AChE, and in its molecular forms over the newborn values start about day 4 and reach maturity by about day 10. The biochemical results correlate well with the massive presence of nerve fibers stained immunocytochemically for ChAT and AChE or enzymatically for AChE in the inner and outer hair cell regions. Ultrastructral studies, however, indicate the presence of only few vesiculated fibers and endings in the inner and outer hair cell regions. The appearance of large, cytologically mature endings occurs only toward the end of the third postnatal week. The discrepancy may be resolved in the electron microscopy using the enzymatic staining for AChE. Labeling is seen on many nonvesiculated fibers and endings in the hair cell regions, suggesting that the majority of the efferent fibers in the perinatal organ may be biochemically differentiated but morphologically immature. The results may imply that the efferents to inner and outer hair cells develop earlier than indicated by previous ultrastructral studies. Moreover, the pattern of development suggests that in the cochlea, as in other tissues, the biochemical differentiation of the efferent innervation may precede the morphological maturation. PMID- 2192020 TI - Variations in the diagnosis, treatment, and prevention of cardiac allograft rejection: the need for standardization? PMID- 2192021 TI - [Recent progress in the evaluation of the dangers of chemical carcinogens]. AB - The paper begins with a brief historical account of the production of cancers through exposure to chemicals, first in humans, then in animals, followed by the identification of chemically defined agents. Such agents have progressively been discovered in the most diverse chemical families. The present classification of chemical carcinogens includes those demonstrated as carcinogenic for humans by adequate epidemiological studies and those considered, on more or less limited basis, as probably or possibly carcinogenic for humans. The first category is divided into three groups: complex mixtures-defined chemicals-industrial operations. The materials and compounds of the last two categories are called "potential carcinogens". The present international trend is to consider them as dangerous for humans as long as their innocuousness has not been demonstrated. The author stresses that the compounds of the three categories are either manufactured or developed by man, or of natural origin. The latter seem, by far, to cause the highest percentage of cancers in humans. Then he develops, in their general outline, the pluridisciplinary methodological approaches in view to revealing the carcinogenic potentialities of compounds to which man can be exposed in various fields (occupational, food, therapeutic, household,...). This leads him to underline the factors of uncertainty involved by the extrapolation to humans of the results of animal experimentation and the importance of observations on groups of humans. He also stresses the multifactors which intervene in the various steps of evolution towards malignancy (initiation, promotion, influence of synergistic or antagonistic factors-role of "free radicals" the type of which is the superoxyde anion radical O2-.). He emphasizes the difficulties of interpretation resulting from the multifactorial nature of the processes of malignancy, as well as the interest of revealing the intimate mechanisms of activity (genotoxic mechanisms with the transformation of certain genes: protooncogenes to oncogenes, epigenetic mechanisms); this demonstration becomes more and more performant thanks to the spectacular progress of basis sciences to which cancer evaluation methodology appeals more and more. Evaluation of carcinogenic risks which, together with early diagnosis, constitutes a fundamental basis of cancer prevention is thus considerably improved. The author is thus led to discuss the possibility of setting threshold values, at least for some types of carcinogenic chemicals. In the end, he insists upon the necessity of an active international cooperation for carcinogenicity studies, either experimental or epidemiological. PMID- 2192022 TI - [Selenium: essentialness, content in food, supplementation, deficiency]. PMID- 2192023 TI - [Indirect spectrophotometric detection by reversed-phase liquid chromatography. Application in drug analysis]. AB - By inclusion of a high U.V. or visible-absorbing component to the mobile phase of a RP-HPLC system, it is possible, after they were separated by chromatography, to detect indirectly and to quantify analytes which do not themselves absorb at the detection wavelength. The principles of this "indirect detection", as well as the parameters which can influence it were studied, and the method was applied to the qualitative and quantitative determination of a lot of compounds used as active substances or as technological adjuvants in drugs. PMID- 2192024 TI - [Intravenous (i.v.) fluid administration systems and incompatibility of injection]. AB - The safety of the injection therapy has to be secured including that of the injection itself as well as that of the equipment used for injection, i.e. i.v. fluid administration systems. The contamination of insoluble particulate matter ascribed to coating of silicone oil over disposable syringe is being solved by the development of syringe using fluoro-resin laminated rubber. In the case of blood administration set and blood bag system, there are some in which the solvent used for adhesion has been eluted. Further, the relationship between the quality of materials of administration set and the adsorption of drugs has become clear. As regards the plastic container for infusion, insoluble particulate matter and adsorption of drugs have become a problem in connection with the quality of materials used and yet the structure of plastic/rubber combined cap is related to the formation of core, thereby making the improvement. In the case of plastic bag, that made of polyethylene does not adsorb drugs so much and the formation of insoluble particulate matter is a little. For the measures of drug interaction of injection, i.v. fluid administration systems have been applied and the safe and effective method of administration of injection will be established along with the development of I.V. delivery system. PMID- 2192026 TI - Intraocular lens experiments before Harold Ridley. PMID- 2192025 TI - Pathogenesis of posterior capsular opacification. Part II: Histopathological and in vitro culture findings. AB - The most interesting sources of information about the pathogenesis of posterior capsular opacification seem to be histopathological studies and in vitro tissue cultures. Since our surgical technique is extracapsular cataract extraction, the explants we used for tissue culture consisted of the anterior capsule epithelial sheet without the equatorial germinative zone. We successfully overcame several problems by using the autologous plasma clot culture method. This medium, considered the optimal one for this type of culture, allowed us to study the heterogeneous behavior of the epithelial cells in culture. Using the plasma clot culture method, we were able to demonstrate in vitro fibroblastic transformation of the epithelial cells. Histopathological findings of particular cases of posterior capsule opacification and immunohistochemistry of the human lens are also reported. PMID- 2192027 TI - The history of obstetric anesthesia. PMID- 2192028 TI - Pain assessment in newborns. PMID- 2192029 TI - Malignant hyperthermia in the postanesthesia care unit: a review of current etiology, diagnosis, and treatment. PMID- 2192030 TI - Pain relief methods in the postanesthesia care unit. PMID- 2192031 TI - Factors influencing semen quality in pigs. PMID- 2192032 TI - Physiological role of seminal components in the reproductive tract of the female pig. AB - In many species the appearance of oestrus is sufficient to ensure that the time of ejaculation, sperm transport and capacitation are balanced with the time of ovulation. In the pig these phenomena vary considerably and require additional regulatory mechanisms which are partly explained by seminal components. Boar semen is rich in oestrogens (up to 11.5 micrograms/ejaculate). Infusion of saline with the addition of oestrogens in physiological amounts increased the myometrial contraction frequency up to 2.5-fold. This effect is explained by a release of PGF-2 alpha immediately after oestrogen infusion. Such an infusion also raises peripheral oestrogen concentrations and an effect on LH release can be demonstrated. Additionally, PGF-2 alpha is measurable in uterine vein plasma after oestrogen infusion and is transferred into the follicular fluid. The effect of oestrogens on LH and follicular PGF-2 alpha is likely to contribute to the timing of ovulation in response to mating. A specific protein of Mr 100,000 110,000 has been detected in boar seminal plasma and it exerts a strong immunosuppressive effect. This protein may be involved in a protection of spermatozoa but also of early embryos against female immunological attack. The addition of such specific compounds to AI doses, in which seminal plasma is diluted, may improve prolificacy. PMID- 2192033 TI - The synthesis and actions of steroids and prostaglandins during follicular maturation in the pig. AB - Our understanding of the synthesis and production of follicular steroids and prostaglandins (PG) in the pig is based largely on in-vitro studies with granulosa and theca interna tissues obtained from Graafian follicles at various stages of maturation. As the follicle enlarges before the LH surge, granulosa cells exhibit a decrease in FSH receptors and are less responsive to FSH in terms of cAMP production. Concurrently, there is an increase in granulosa and thecal cell LH receptors associated with an increase in responsiveness to LH and an increase in steroid production. Both granulosa and thecal cells produce oestrogen and progesterone, the rates of production being dependent on the stage of maturation of the follicle and substrate availability. Thecal cells are the principal source of androgens and control oestrogen synthesis by providing aromatizable substrate. After exposure to LH/hCG in vivo, both cell types lose the ability to produce oestrogen in vitro. These studies support the two-cell, two-gonadotrophin hypothesis of ovarian steroidogenesis. In vitro, granulosa and thecal cells exhibit an increased ability to produce PGE-2 and PGF-2 alpha after exposure to LH/hCG in vivo. Follicular PG production appears to be regulated by arachidonic acid availability and PG synthetase activity. In vivo, the follicular fluid concentrations of PGE-2 and PGF-2 alpha increase markedly at the time of ovulation. The increases in PG levels and ovulation can be blocked by indomethacin, an inhibitor of PG synthesis. These studies provide convincing evidence for an intrafollicular source of PGs and are consistent with the hypothesis that LH induces an increase in PG production that is essential for rupture of the follicle. Steroids act on the follicle through autocrine and paracrine mechanisms to modulate follicular growth and differentiation and to regulate steroidogenesis. PG actions on the follicle appear to be exerted via effects on contractile elements of the theca externa, blood vessels and on collagenolytic and other proteolytic enzymes. PMID- 2192034 TI - Local regulatory factors controlling folliculogenesis in pigs. PMID- 2192035 TI - Evidence for and implications of follicular heterogeneity in pigs. AB - Follicular heterogeneity has been demonstrated in both naturally cyclic and PMSG stimulated immature gilts in that follicles in the selected ovulatory population differ in size by up to 2 mm and show marked variability in steriod content and gonadotrophin binding ability. This biochemical and morphological asychrony continued into the immediate preovulatory phase and changes in response to the LH surge did not always occur simultaneously even in the same follicle or in all follicles within an ovary. It is suggested that these differences in follicular maturation immediately before ovulation may result in heterogeneity in the population of corpora lutea. Following oestrus or hCG administration, oocyte maturation was again not completely synchronous in all follicles within an animal. It is proposed that follicular heterogeneity has implications for oocyte maturation and early embryonic development. PMID- 2192036 TI - Uterine and ovarian countercurrent pathways in the control of ovarian function in the pig. PMID- 2192037 TI - Regulation and action of gonadotrophins in pigs. AB - Gonadotrophins, synthesized and secreted from the basophils of the adenohypophysis, bind to various target cells and elicit a wide variety of responses. Specific receptors for gonadotrophins have been found on plasma membranes of thecal, granulosa, luteal, endometrial and myometrial cells in the female and on Leydig and Sertoli cells in the male. Gonadotrophins exert their effects through various intracellular second messengers and control biosynthetic pathways of steroid production in responsive cells. Gonadotrophins stimulate growth and development of antral follicles in the female. PMSG, FSH, or hourly pulses of GnRH, LH or a combination of LH and FSH induce follicular growth and development in prepubertal gilts and lactating and(or) anoestrous sows. The number of follicles that develop to ovulatory size in response to PMSG and FSH is dose-dependent, but pulsatile treatment with GnRH or gonadotrophins results in an ovulation rate similar to that observed during spontaneous follicular development. Endocrine changes resulting from treatments that induce follicular growth and development are similar to those observed during the follicular phase of the oestrous cycle. Hypophysectomy, hypophysial-stalk transection, active and passive immunization against GnRH, and active immunization against LH impair reproduction by interfering with normal follicular development in the female. Gonadotrophins, administered to gilts as repeated injections of whole pituitary extract or as pulses of GnRH agonist, do not stimulate follicular growth in gilts actively immunized against GnRH. Similarly, PMSG is ineffective in inducing follicular growth and development in gilts actively immunized against GnRH and after hypophysectomy or hypophysial-stalk transection. In contrast, PMSG is effective for inducing follicular development in hypophysial stalk-transected pigs when pulses of GnRH are given simultaneously with the PMSG. These results suggest that agents in addition to the gonadotrophins are required for the full complement of follicular growth, recruitment and development. Insulin, growth factors and steroids modify the response of cells to the gonadotrophins and may mediate these effects. Other possibilities include substances released from the pituitary gland or GnRH-like peptide(s) produced by the ovary that act as autocrine or paracrine regulators of follicular development. Gonadotrophins stimulate testicular function in the male. Active immunization of mature boars against GnRH or LH results in testicular atrophy, depressed steroidogenic and spermatogenic functions and impaired libido. Treatment of boars immunized against GnRH with hCG restores steroidogenic function of the testes as evidenced by testosterone production. Gonadotrophins also exert an influence in the central nervous system. Administration of hCG intramuscularly or intracranially blocks the oestrogen-induced preovulatory LH surge in ovariectomized pigs via a short loop feedback control mechanism.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2192038 TI - Maturation of pig oocytes in vivo and in vitro. PMID- 2192039 TI - Fertilization of pig eggs in vivo and in vitro. PMID- 2192040 TI - Cloning of embryos. AB - Nuclear transfer for the study of differentiation in amphibians has been used since the 1950s, but not until recently have the same procedures been applied successfully to some mammals. Nuclear transfer, as developed for the amphibian, is successful in sheep, cattle, rabbit, and pig, but not mouse embryos. This fact is discussed in relation to the species-specific timing of the activation of the zygotic genome. Nuclear transfer to an oocyte presumably results in a genomic reprogramming of the transferred nucleus. The limits of differentiation that can be reprogrammed have yet to be determined. Since the cells of early embryos are thought to have identical nuclear genomes, early embryos can be used as a source of donor nuclei; and, when combined with serial nuclear transfer, can theoretically produce an unlimited number of identical offspring. Cloning by splitting does not result in a reprogramming of the genome and is limited in the number of identical offspring that can result. Here we discuss some of the factors to consider concerning micromanipulation and nuclear reprogramming and how they relate to other embryo technologies. PMID- 2192041 TI - Expression and performance in transgenic pigs. AB - Recent research clearly shows that fusion genes can be microinjected into a pronucleus of an ovum and integrate into the pig genome. Animals with such fusion genes are called 'transgenic'. The percentage of injected ova that developed into transgenic pigs varied among experiments from 0.31% to 1.73%. The percentage of transgenic pigs that expressed the fusion gene ranged from 17% to 100%. Eleven different regulatory sequences have been used for fusion genes transferred into pigs. Some of these regulatory sequences directed strong gene expression, but control over level of expression was inadequate. Other regulatory sequences directed weak expression, but imparted only brief spikes of induced expression. The predominant gene coding sequences transferred were for growth-related hormones. Elevation of growth hormone (GH) in expressing transgenic pigs enhanced plasma concentrations of insulin-like growth factor-I (IGF-I), insulin, and glucose, improved feed efficiency about 15%, and markedly reduced subcutaneous fat compared to nontransgenic siblings. Growth rate was enhanced in some transgenic GH pigs but not in others, possibly due to dietary limits. The 'over expression' of GH was detrimental to the general health of most transgenic pigs. The most prevalent problems were lethargy, lameness, and gastric ulcers. Gilts that expressed foreign GH genes were anoestrous. Boars that expressed foreign GH genes lacked libido, but their semen was fertile when used by artificial insemination. Six different fusion genes have been transmitted from transgenic founders to progeny. Most of the transgenic pigs that produced progeny transmitted the fusion gene as an autosomal dominant trait to about half of their progeny. Regulatory sequences that will permit full control of gene expression must be developed before the full potential of gene transfer in pigs can be realized. PMID- 2192042 TI - Causes and consequences of early embryonic diversity in pigs. AB - Within 14 h of ovulation, follicular development in gilts was skewed towards a majority of mature follicles, based on their endocrine milieu. Oocyte maturation was also skewed, with a majority of the oocytes being meiotically more developed than the rest. Similarly, the pattern of ovulation in gilts was such that 70% of the follicles ovulated during a short period of time, while most of the remaining 30% ovulated over a more protracted period. This majority/minority pattern of both oocyte development and ovulation paralleled the distribution of development among 1-cell litter-mate embryos. Furthermore, oocytes of follicles predicted to ovulate first became the more developed embryos, while oocytes from later ovulating follicles became the lesser developed embryos. When these later ovulating follicles were destroyed by electrocautery, diversity in embryonic morphology was reduced by Day 12, and this reduction resulted from elimination of the lesser developed embryos. Genetic factors might also affect embryonic disparity, as SLA (swine leucocyte antigen complex) haplotype affected cleavage rates of embryos from miniature pigs. Results of various embryo transfer experiments demonstrated that the more developed embryos within a litter have a competitive advantage for survival over their less developed contemporaries. These lesser developed embryos, however, were just as viable as the more developed embryos after asynchronous transfer to recipients displaying onset of oestrus 1 day after the donors. The more developed embryos within the litter, by synthesizing more oestradiol than the smaller embryos, advanced uterine secretions. As a result, the lesser developed embryos probably became more susceptible to this new environment and eventually died in an asynchronous environment. Therefore, we suggest that early embryonic mortality directly relates to sequences of oocyte and follicular maturation, as oogenesis directs embryogenesis. PMID- 2192043 TI - Embryonic and uterine development during early pregnancy in pigs. AB - Comparison of the timing of pig preimplantation development, alterations in the ultrastructure of embryonic germ layers, and cytological changes of the uterine epithelial cells leads to the supposition that a close relationship exists between embryonic and uterine development during early pregnancy. The results of in-vitro studies of embryonic development and of experiments concerning asynchrony between embryos and uterine environment confirm this supposition, especially as far as the post-hatching period is concerned. It is suggested that successive steps in embryonic germ layer differentiation may induce specific developmental events and secretory activity of the embryos. A mutual influence of maternal and embryonic tissues appears to exist, but we can only speculate about the causes of many of the described phenomena. PMID- 2192044 TI - Regulation of uterine and conceptus secretory activity in the pig. AB - Evidence is presented for the involvement of a number of specific uterine- and conceptus-derived proteins in endometrial differentiation and conceptus or fetal development. These secretory proteins include mitogens (insulin-like growth factor-I and -II, epidermal growth factor, uterine luminal fluid mitogen), binding and transport proteins (uteroferrin, insulin-like growth factor and retinol binding proteins, respectively), protease inhibitors (antileukoproteinase, plasmin/trypsin inhibitor), and trophoblastic specific proteins. Using immunological reagents and specific complementary DNA (cDNA) probes, the tissue origins of several of these proteins have now been identified. In addition, the temporal regulation of messenger RNA (mRNA) production for a number of these proteins has been elucidated. The results suggest that although circulating and locally produced steroid hormones may be involved in regulating the synthetic abilities of these tissues during pregnancy, other, as yet undefined, factors may also mediate these activities. In this paper we present a review of the current knowledge pertaining to the identity, physiological regulation and potential functions of pig maternal and conceptus secretory proteins during pregnancy. PMID- 2192045 TI - Embryonic steroids and the establishment of pregnancy in pigs. AB - In the pig, establishment of pregnancy begins about 11-12 days after the start of oestrus. The ability of pig conceptuses to synthesize and release oestrogens during this period, as well as the ability of exogenous oestrogens to induce pseudo-pregnancy when administered from Day 11-15 of the oestrous cycle, provide evidence for an involvement of oestrogen in the maternal recognition of pregnancy in the sow. Oestrogen derived from the conceptus or from administration to cyclic gilts stimulates uterine secretion of calcium and specific polypeptides on Day 11 12. The specific roles for the uterine secretory response to oestrogen in the maintenance of pregnancy are unknown. However, it has been proposed that oestrogen prevents luteolysis in the sow through reorientation of endometrial prostaglandin release, i.e. into the uterine lumen rather than into the uterine vasculature. Oestrogen may interact with prolactin and/or conceptus secretory proteins to shift the direction of prostaglandin movement. Although conceptus oestrogen synthesis triggers a number of uterine secretory events on Day 11, a second sustained phase of oestrogen stimulation from Day 14 to 18 appears to be necessary for luteal maintenance beyond Day 25. Pig conceptuses synthesize and release large amounts of oestrogens between Days 14 and 18 of pregnancy. Conceptus oestrogens are clearly involved with the establishment of pregnancy. However, the conceptus also secretes a number of biologically active substances such as catechol oestrogens, prostaglandins and polypeptides which could interact with oestrogen to prevent luteolysis. The roles of these factors in control of vascular permeability, blood flow, placental attachment and immunological protection certainly indicate that, in addition to oestrogens, other factors are involved in the establishment of pregnancy in pigs. PMID- 2192046 TI - Hypothalamic control of gonadotrophin and prolactin secretion in pigs. PMID- 2192047 TI - Differentiation of sexual behaviour in pigs. AB - Behaviour in pigs is sexually dimorphic as early as 1 month of age; mounting of penmates is observed more frequently for males than for females. This mounting reaches its highest frequency during the 2nd month of life and then declines to a low frequency in prepubertal pigs. During the prepubertal period (3-5 months of age), bipotentiality of sexual behaviour is apparent in boars because they will not only mount oestrous females but they are also receptive to mounts by older, mature boars. If males are castrated during neonatal development (first 2 months of life) and treated acutely with oestrogen during adulthood, they display sexual behaviour that is characteristic of females; i.e. show a selective preference to remain near mature boars in a choice test, are receptive to mounts by mature boars, and have a short latency to receptivity after contact with a mature boar. Males that are castrated at 6 months of age or later, or males that are castrated neonatally and treated chronically with oestrogen or testosterone during the prepubertal period, display significantly less female behaviour after acute oestrogen treatment than do males castrated neonatally. Additionally, exposure of females to elevated testosterone during early fetal development results in no detectable changes in oestrous behaviour as adults. These observations support the hypothesis that defeminization of sexual behaviour in boars occurs as a result of elevated testicular steroids during pubertal development. The limited data available on masculine sexual behaviour in pigs indicate an activational role for gonadal steroids with little evidence for true masculinization per se. After prolonged testosterone treatment of mature females or males that are castrated before puberty, considerable courtship and mounting behaviours are exhibited by these individuals when placed with oestrous females. Studies have not evaluated differential sensitivity of such animals to dosage or duration of testosterone treatment. Differentiation of sexual behaviour in boars therefore involves primarily a loss of sensitivity to display female-typical behaviours. Presently, pigs differ from other mammals that have been investigated because sexual differentiation of reproductive behaviour occurs during pubertal development and not during gestation. PMID- 2192048 TI - Mechanisms mediating the stimulatory effects of the boar on gilt reproduction. PMID- 2192049 TI - Role of prolactin in the regulation of ovarian function in pigs. PMID- 2192050 TI - Behavioural responses affecting gilt and sow reproduction. AB - Behavioural responses can have direct effects on reproduction when the performance of the behaviour contributes to productivity (e.g. achievement of copulation). Alternatively, there are indirect effects where a behavioural change is insufficient to allow adaptation to an environmental change and so the animal has to resort to physiological mechanisms with potential adverse effects on productivity. Boar contact has substantial effects on a number of female behaviours that can directly affect her productivity. Either daily introduction to a boar or continuous housing adjacent to boars is effective in stimulating the onset of oestrus in weaned sows. In addition, daily boar contact is necessary to maintain ovarian activity in post-pubertal gilts. The efficiency of the back pressure test (BPT) in detecting sexually receptive females depends on females receiving intense and close boar contact at the time of testing. However, there are situations in which continuous stimulation from boars may adversely affect sexual behaviour; continuous housing of gilts adjacent to boars, with a wire-mesh division separating them, reduces the efficiency of detection of oestrus by means of the BPT or a boar. There is some evidence to indicate that housing weaned sows adjacent to boars may adversely affect the duration of oestrus but not detection rate of oestrus. The effects of female contact on productivity are generally indirect with physiological responses (rather than behavioural responses) to suboptimal group size, space allowance or housing system predominantly responsible for any adverse effects on reproduction. The literature on the effects of individual or group housing on reproduction is equivocal, but there is a trend for a reduced conception rate or pregnancy rate in individual housing. Group size and space allowance may affect the efficiency of detection of oestrus. A space allowance of 1 m2/animal appears to affect detection of oestrus adversely for gilts, probably via a chronic stress response associated with overcrowding. The literature on the effects of group size on sexual behaviour of female pigs is also equivocal, perhaps because in some studies there were suboptimal space allowances. Nevertheless, there appear to be problems with detection of oestrus in very small groups and in large groups. The effects of human contact on female reproduction are indirect. There are no direct effects on the sexual behaviour of female pigs and the effects on reproduction are probably mediated by a chronic stress response. High levels of fear of humans may depress the reproductive performance of pigs and this fear response is probably affected by the behaviour of the stockperson.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2192051 TI - Behavioural perspectives on piglet survival. AB - Litters of domestic piglets show strong sibling competition, large differences among litter-mates in birth weight and rate of growth, and, in the absence of human intervention, a high mortality rate. This combination of traits suggests that pigs are using a reproductive strategy similar to that of certain bird species which produce one or more small 'spare' young whose death or survival is determined by sibling competition. Death through competition is natural in such species. Prevention of death requires the early identification and separate rearing of unsuccessful competitors. The major behavioural pathways leading to piglet deaths are considered to be malnutrition through unsuccessful suckling behaviour, and crushing of piglets by the sow. Crushing involves two distinct behavioural sequences: posterior crushing (beneath the sow's hind quarters) and ventral crushing (beneath the udder and rib cage). Farrowing crates are designed to prevent posterior but not ventral crushing. Malnourished piglets appear to be more vulnerable to crushing, perhaps because persistent suckling attempts cause them to spend more time near the sow. Prevention of crushing thus requires a reduction in malnutrition, not merely restriction of the sow's movements. Under certain conditions, dehydration may be an important but neglected aspect of malnutrition. Some litters of piglets have much higher death losses than others, presumably because of risk factors that apply to the litter as a whole. Early malnutrition, resulting from hypogalactia in the sow in the first days after farrowing, appears to be an important risk factor. Farrowing difficulties leading to piglet hypoxia during the birth process may be another. Risk factors that affect whole litters deserve greater emphasis in future research. PMID- 2192053 TI - Nutritional strategies to optimize reproduction in pigs. PMID- 2192052 TI - Endocrinology of the lactating and weaned sow. PMID- 2192054 TI - Metabolic influences on hypothalamic-pituitary-ovarian function in the pig. PMID- 2192055 TI - Reevaluating the therapeutic approach to rheumatoid arthritis: the "sawtooth" strategy. AB - A new therapeutic philosophy for management of rheumatoid arthritis (RA) is required, since the traditional "pyramidal" strategy has failed to measurably improve longterm outcome. This paper attempts a conceptual overview of the problem and suggests an available solution. The increased repertoire of potentially disease-modifying drugs (DMARD) allows a new creativity, and toxicity with these agents has been less than expected. Yet, clinical improvement observed initially with these agents over the first 10 to 20 months of treatment is eventually lost and accelerated increase in disability follows. Given these observations, a "sawtooth" strategy is proposed, with 6 principles: early DMARD use, continual serial DMARD use, regular quantitative monitoring of disability to detect insidious progression, setting a disability ceiling for the individual patient, sequential change in DMARD treatment when the ceiling is reached, and deployment of analgesics and NSAID as adjunctive rather than "first line" therapy. This strategy offers the potential for long-term disease modification with reasonable toxicity levels. PMID- 2192056 TI - Drug-drug interactions with antirheumatic agents: review of selected clinically important interactions. AB - Drug therapy for rheumatoid arthritis (RA) often requires the use of more than one drug, thus drug-drug interactions are very likely in this patient population. We discuss the pharmacokinetic and pharmacodynamic mechanisms involved in drug drug interactions. Our review focuses on selected examples involving drugs used to treat RA and other antirheumatic drugs [e.g., methotrexate and nonsteroidal antiinflammatory drugs (NSAID)] or with other therapeutic classes of drugs (e.g., NSAID and warfarin). Studies and case reports of drug-drug interactions with antirheumatic drugs are critically evaluated and the potential clinical implications are discussed. PMID- 2192057 TI - 50 years of antirheumatic therapy: the prognosis of rheumatoid arthritis. AB - The longterm prognosis of rheumatoid arthritis (RA) is bad. All markers of outcome--mortality, functional ability, cumulative pain, economic costs, and adverse reactions to therapy--are unfavorably altered in this illness. But considerable evidence exists that pharmacologic and nonpharmacologic interventions can alter the course of RA by decreasing work and functional disability, and improving the quality of life of those with RA. Therapy alters the slope of RA decrement, permanently or intermittently. Such changes, however, are difficult to measure in short-term cross-sectional studies, and the effect of treatment may be underestimated. PMID- 2192058 TI - Longterm experience with low dose weekly methotrexate in rheumatoid arthritis. AB - Longterm prospective studies (several of greater than 5 years' duration) report sustained efficacy with low dose weekly methotrexate. A "steroid-sparing" effect has been noted with methotrexate in 2 of the studies. Of 230 patients enrolled in prospective studies, only 8% stopped therapy due to toxicity and 3% due to lack of efficacy. Life table analysis projected that 63% of these patients would receive therapy for 6 years. Even though adverse experiences were frequent, serious reactions have been rare in the published studies. PMID- 2192059 TI - Hepatotoxicity of antirheumatic drugs. AB - The central role of the liver in drug metabolism makes it vulnerable to toxic injury. Drug induced liver injury may mimic any of the naturally occurring liver diseases. The rheumatic diseases themselves may have liver disease associated with them, making it especially difficult to recognize hepatotoxicity. Nevertheless, hepatotoxicity has been reported with most of the drugs used to treat the rheumatic diseases. Because the reactions may be fatal, it is important to recognize hepatotoxicity. The current drug development process does not and cannot identify drugs with a low incidence of hepatotoxicity. Therefore, it is necessary for physicians to be aware of the potential of any drug to cause liver injury. Serious hepatotoxicity, however, can usually be prevented by awareness and appropriate monitoring. Most of the nonsteroidal antiinflammatory drugs, azathioprine and dantrolene should be monitored at monthly intervals for the first 6 months of therapy. Methotrexate should be monitored indefinitely. It remains unrealistic to expect premarketing studies to identify hepatotoxicity and, thus, surveillance is needed for all newly marketed drugs. PMID- 2192060 TI - Streptococcal serotypes newly associated with epidemic post-streptococcal acute glomerulonephritis. AB - The increasing incidence of reported scabies in Trinidad, from 24.2/100,000 population in 1984 to 59.5/100,000 in 1985, led to a careful monitoring in 1986 of all patients with post-streptococcal acute glomerulonephritis (PSAGN). There were 181 cases of PSAGN; 84 beta-haemolytic streptococcal isolates from 72 patients were sent to the Central Public Health Laboratory, Colindale, for grouping and serotyping. The PSAGN epidemic of 1986 was bimodal. Streptococci of M-type 73 appeared to be associated with the first phase (March-May) and comprised 20% of the isolates serotyped. New to Trinidad, streptococci of M-type 48 (4% of the isolates serotyped) preceded the first phase of the epidemic and were isolated from two patients with PSAGN. Provisional type (PT) 5757, also new to Trinidad, had been previously identified only among serotypes from the United Kingdom and the Federal Republic of Germany. This type was isolated from seven patients, in six from skin lesions and in one from the throat. PT 5757 occurred during the first wave of the epidemic and comprised 14% of the strains serotyped. Thus, the first wave of the bimodal epidemic involved serotypes M73, M48 and PT 5757. The more intense second phase (July-October) was associated with the previously documented nephritogenic M-type 55. PMID- 2192061 TI - Instability of characteristics amongst coagulase-negative staphylococci causing endocarditis. AB - Variation in typing of clinically significant isolates of coagulase-negative staphylococci (CNS) was determined by five typing methods with 143 isolates obtained from 19 patients over periods from 2 days to 1 year. In only one case did all isolates give exactly the same typing pattern by all five tests. No single method, or simple combination, provided a ready means of confirming the relatedness of separate isolates. The most frequently useful tests were antibiotic susceptibility and extrachromosomal DNA banding patterns. However, the results of biotyping, serotyping and phage typing were also helpful in showing the relationship between different isolates from a given patient. In most cases a core pattern varying by the gain or loss of a small number of features, characterised a given patient's isolates. In two causes, apparently radical changes in the infecting organism were observed, and confirmed by restriction endonuclease analysis. Care should be taken when successive isolates of CNS show distinct typing differences in deciding their clinical relevance. PMID- 2192062 TI - The identification of pathogenic yeast strains by electrophoretic analysis of their chromosomes. AB - Epidemiological studies require characterisation of pathogenic yeasts at and below the species level. The chromosomes of 130 strains of four pathogenic species of the genus Candida, isolated from clinical material, were separated by pulsed field electrophoresis with the clamped homogeneous electric field (CHEF) technique. Each species was characterised by a distinct electrophoretic karyotype (EK). Furthermore, smaller variations of the EK amongst strains belonging to the same species appeared to offer a useful means of strain differentiation. A karyotyping system is proposed for C. albicans. The EKs were assigned to a code of four numbers which designated the number of bands that could be resolved in each of four sets of chromosomes. Morphotypes of the colonies of C. albicans on malt agar plates, which did not correlate with the EK, could provide a complementary means of strain characterisation in epidemiological studies. PMID- 2192063 TI - Characterisation of a unique ceftazidime-hydrolysing beta-lactamase, TEM-E2. AB - A strain of Klebsiella oxytoca, originally isolated in Liverpool in 1982, has been found to produce a novel transferable beta-lactamase, TEM-E2. This enzyme confers resistance to ceftazidime and focused as a doublet band with an iso electric point (pI) of 5.3. The strain also produced the TEM-1 beta-lactamase. Both TEM-1 and TEM-E2 beta-lactamases were encoded by a transferable 103 kb plasmid; these two enzymes also had similar molecular weights, were inhibited by clavulanic acid, and hydrolysed ampicillin, carbenicillin and cephaloridine at similar rates. However, unlike the TEM-1 enzyme, the TEM-E2 beta-lactamase hydrolysed ceftazidime and cefotaxime with similar efficiency, although it conferred much greater resistance to ceftazidime in the host strain. This is the earliest documented example of a TEM-like enzyme which confers transferable resistance to ceftazidime and related cephalosporins. PMID- 2192064 TI - The pathogenesis of urinary tract infections associated with Escherichia coli, Staphylococcus saprophyticus and S. epidermidis. AB - A model was developed in mice to study the pathogenesis of urinary tract infections caused by Staphylococcus saprophyticus strains LM-1 and LM-2, Escherichia coli SP444 and S. epidermidis E001. Murine urinary bladders were inoculated with 10(8) bacteria via a temporary urinary catheter and samples of urine and bladder were removed at days 1, 3, 5 and 10 after inoculation. They were examined both bacteriologically and by electronmicroscopy. Severe disruption of the urothelium was present immediately and the urothelium had become oedematous and ulcerated with increased urothelial exfoliation. Disruption of the urothelium was similar with all the four pathogens studied. The three strains of coagulase-negative staphylococci preferentially attached to the urothelial cell tight junctions and were not associated with polymorphonuclear leucocytes. In comparison, E. coli SP444 was randomly attached over the entire urothelium and was often in association with macrophages. Phagocytosis of E. coli by superficial urothelial cells also occurred. PMID- 2192065 TI - Detection of cytotoxic necrotising factor (CNF) in extracts of Escherichia coli strains by enzyme-linked immunosorbent assay. AB - An enzyme-linked immunosorbent assay (ELISA) consisting of a double sandwich technique with rabbit and sheep antibodies, was developed for the detection of cytotoxic necrotising factor (CNF) in extracts of Escherichia coli strains. The assay was evaluated by comparison with the results obtained with an assay based on toxicity for HeLa cell cultures. In a study of extracts of 27 CNF+ and 45 CNF- strains obtained by ultrasonic disintegration, no false positive and only three false negative results were recorded; the latter were obtained with strains that produced less CNF than any of the others examined. Frozen-thawed extracts contained about four times more CNF cytotoxic activity than extracts prepared ultrasonically; the testing of 54 CNF+ and 68 CNF- frozen-thawed extracts resulted in no false positive and only one false negative response. Whichever type of extract was used, no significant cross-reaction was observed with heat labile (LT) or heat stable (ST) enterotoxin, verotoxin (VT1, VT2), haemolysin, or Vir cytotoxin. PMID- 2192067 TI - Peter Harris Award lecture. History and prospects in calcium antagonist research. PMID- 2192066 TI - Observations concerning topology and locations of helix ends of membrane proteins of known structure. AB - Hydropathy plots of amino acid sequences reveal the approximate locations of the transbilayer helices of membrane proteins of known structure and are thus used to predict the helices of proteins of unknown structure. Because the three dimensional structures of membrane proteins are difficult to obtain, it is important to be able to extract as much information as possible from hydropathy plots. We describe an "augmented" hydropathy plot analysis of the three membrane proteins of known structure, which should be useful for the systematic examination and comparison of membrane proteins of unknown structure. The sliding window analysis utilizes the floating interfacial hydrophobicity scale [IFH(h)] of Jacobs and White (Jacobs, R.E., White, S. H., 1989. Biochemistry 28:3421-3437) and the reverse-turn (RT) frequencies of Levitt (Levitt, M., 1977, Biochemistry 17:4277-4285). The IFH(h) scale allows one to examine the consequences of different assumptions about the average hydrogen bond status (h = 0 to 1) of polar side chains. Hydrophobicity plots of the three proteins show that (i) the intracellular helix-connecting links and chain ends can be distinguished from the extracellular ones and (ii) the main peaks of hydrophobicity are bounded by minor ones which bracket the helix ends. RT frequency plots show that (iii) the centers of helices are usually very close to wide-window minima of average RT frequency and (iv) helices are always bounded by narrow-window maxima of average RT frequency. The analysis suggests that side-chain hydrogen bonding with membrane components during folding may play a key role in insertion. PMID- 2192068 TI - Translation of Otto Frank's paper "Die Grundform des Arteriellen Pulses" Zeitschrift fur Biologie 37: 483-526 (1899). PMID- 2192069 TI - Dose-response relationship of ozone-induced airway hyperresponsiveness in unanesthetized guinea pigs. AB - The effect of ozone dose (the product of ozone concentration and exposure time) on airway responsiveness was examined in unanesthetized, spontaneously breathing guinea pigs. Airway responsiveness was assessed by measuring specific airway resistance (sRaw) as a function of increasing concentration of inhaled methacholine (Mch) aerosol (the concentration of Mch required in order to double the baseline sRaw: PC200Mch). The airway responsiveness was measured before and at 5 min, 5 h, and 24 h after exposure. A 30-min exposure to 1 ppm ozone (dose 30 ppm.min) did not change PC200Mch at any time after exposure. Both a 90-min exposure to 1 ppm ozone and a 30-min exposure to 3 ppm ozone, which are identical in terms of ozone dose (90 ppm.min), decreased PC200Mch to a similar degree. A 120-min exposure to 3 ppm ozone (360 ppm.min) produced a much greater decrease of PC200Mch at 5 min and 5 h after exposure, compared with low-dose exposure. There was a significant correlation between ozone dose and the change in airway responsiveness. In all groups, the baseline sRaw was increased by approximately 50% at 5 min after exposure, but there was no correlation between the changes in PC200Mch and the baseline sRaw. This study suggests that ozone-induced airway hyperresponsiveness in guinea pigs is closely related to ozone dose. PMID- 2192070 TI - U-shaped dose-response curves: their occurrence and implications for risk assessment. AB - A class of curvilinear dose-response relationships in toxicological and epidemiological studies may be roughly described by "U-shaped" curves. Such curves reflect an apparent reversal or inversion in the effect of an otherwise toxic agent at a low or intermediate region of the dose continuum. Several examples of U-shaped dose-response functions are presented to illustrate the variety of agents and end points that can follow this form. Such findings are not thought to represent a unitary phenomenon, but may be explained through numerous possible principles or mechanisms, some of which are illustrated and discussed in general terms. U-shaped dose-response curves raise important issues for toxicological and environmental health risk assessments, particularly in the identification of no-observed-effect levels and in the evaluation of multiple outcomes and the tradeoffs between potential risks and benefits of a given agent. It is especially important to avoid focusing exclusively on an apparent improvement in one end point and failing to consider other, possibly deleterious effects of the same agent. PMID- 2192071 TI - The basis of antibiotic resistance in bacteria. AB - The ability of bacteria to resist the inhibitory and lethal actions of antibiotics is a major clinical problem, and has been observed with every antimicrobial agent. In this article, the major mechanisms of antibiotic resistance are reviewed, and the clinical relevance of such resistance in selected bacteria is discussed. PMID- 2192072 TI - Haemophilus influenzae type B and its role in diseases of the head and neck. AB - Haemophilus influenzae is a common pathogen in infections of the head and neck. Although most mucosal infections (otitis media, sinusitis) are caused by non encapsulated organisms, invasive disease (meningitis, periorbital cellulitis, epiglottis) is caused by type B encapsulated organisms. Bacteremia is common with H. influenzae type B infections and therapy with parenteral antibiotics is indicated. A vaccine against H. influenzae type B given at 18 months of age is now part of the routine childhood immunization schedule. Chemoprophylaxis with rifampin is recommended for at-risk contacts of patients with invasive type B disease. This review examines the bacteriology, pathogenesis, immunity, and disease manifestations of H. influenzae. Appropriate diagnostic methods, antimicrobial therapy, and recommended chemoprophylaxis and immunoprophylaxis are presented. PMID- 2192073 TI - The efficacy of pulse-dosed antibiotic therapy in the management of persistent otitis media with effusion. AB - Consensus has been achieved supporting the efficacy of antimicrobials in the management of acute otitis media with effusion (OME). No such agreement has been reached into medical management of the patient in whom middle ear effusion (MEE) persists beyond the conventional 10- to 14-day treatment cycle. This study is designed to demonstrate the efficacy of antibiotics administered in a single daily dose in the management of persistent otitis media with effusion (POME). Seventy-nine subjects who had MEE in 116 ears after conventional therapy were randomized into medication and placebo groups and followed by the authors on a blinded basis. The results demonstrate the efficacy of pulse-dosed antibiotics in the management of POME. Prevention of relapses during therapy was responsible for the superior outcome for children in the treatment group. PMID- 2192074 TI - Pediatric human immunodeficiency virus infection: an otolaryngologist's perspective. AB - Children with human immunodeficiency virus (HIV) frequently have recurrent otitis media, chronic rhinorrhea, parotitis, cough and other common pediatric otolaryngologic problems. As these complaints often occur before more unusual opportunistic infections or pulmonary conditions prompt a diagnosis of acquired immunodeficiency syndrome (AIDS), members of our specialty are liable to see HIV positive children before infection with the virus has been recognized. Children with HIV infection are also likely to be referred to us after diagnosis, as is any immunosuppressed child with otolaryngologic infections. These children may require procedures such as bronchoscopy, sinus irrigations or tympanocentesis. The subject of this review is the natural history of pediatric HIV infection with special emphasis on otolaryngologic manifestations and recommendations for safe techniques of examination and treatment. PMID- 2192075 TI - Parotid gland enlargement in HIV infection: clinical/imaging findings. AB - Parotid gland enlargement with or without facial paralysis may be the presenting clinical manifestation of AIDS. Submandibular involvement may occur as well. Failure to recognize this association may lead to inappropriate or unnecessary intervention in the investigation and treatment of the salivary gland enlargement. In this paper, we discuss the role of imaging techniques in the investigation of salivary gland enlargement, and identify the specific radiologic signs found in HIV infection. Demonstration of intraparotid or submandibular gland cysts with focal intraparotid mass lesion(s) on imaging may help to differentiate parotid gland enlargement due to HIV infection from the many other causes of parotid enlargement. PMID- 2192076 TI - Streptococcus pneumoniae acute suppurative parotitis in a patient with Sjogren's syndrome. AB - A case of suppurative parotitis due to Streptococcus pneumoniae is reported in a patient with Sjogren's syndrome. The rarity of this condition is noted by a review of the literature. PMID- 2192077 TI - Wound infection in head and neck surgery: prophylaxis, etiology and management. AB - Antibiotic prophylaxis in clean-contaminated major head and neck surgery is mandatory. Many prospective, randomized and double blind studies have established the efficacy of antibiotics against a large spectrum of bacteria. Prophylaxis should be initiated prior to surgery, and prolonged administration of antibiotics beyond the first 24 hours following surgery is unnecessary. The experience of the Eye and Ear Hospital of Pittsburgh is presented along with other studies concerning the effect of different regimens on wound outcome. The pathophysiology, bacteriology, evaluation and treatment of a postoperative infection are discussed, emphasizing the importance of gentle tissue handling and meticulous surgical technique. PMID- 2192078 TI - Infections of the fascial spaces of the neck. AB - Infections of fascial spaces of the neck continue to be life-threatening events. The frequency of these infections has been drastically reduced by antibiotics and good dental care. Intravenous drug use and immunosuppressed states have altered the modern presentation of these infections. This paper represents a review of these conditions, the anatomical and microbiological factors involved and the treatment. Attention is given to the use of modern imaging and contemporary antibiotic management. A clear understanding of regional anatomy remains critical to the proper resolution of these conditions. PMID- 2192079 TI - Infection of facial bones. PMID- 2192080 TI - Anomalous systemic and pulmonary venous pathways diagnosed in utero by ultrasound. AB - Anomalies of systemic and pulmonary venous return are found as either isolated lesions or as part of a complex cardiac malformation. Specifically, these venous pathway malformations are associated frequently with the cardiac defects in asplenia or polysplenia. This report describes the prenatal ultrasound diagnosis of both anomalous pulmonary and systemic venous drainage in three late gestation fetuses with a splenic syndrome and complex congenital heart disease. In addition, the utility of color-flow Doppler as an aid in making the diagnosis is emphasized. PMID- 2192081 TI - Evaluation of abdominal lymph nodes by ultrasound. AB - To evaluate the significance of sonographically detected abdominal lymph nodes, the medical records of 100 consecutive patients with abdominal lymphadenopathy were reviewed. The number of lymph nodes, their localizations, dimensions, shape, and architecture were recorded. One hundred ninety-four lymph nodes were found in 63 patients known to have a malignancy; 68 lymph nodes were found in 37 patients with benign diseases. The localization, size, shape, and architecture of all lymph nodes were evaluated. Of the different variables we studied in the evaluation of the abdominal lymph nodes, echogenicity, shape, age of the patient, and a periaortic localization are helpful in the differentiation between benign and malignant involvement. There remains a considerable overlap; in these cases fine-needle aspiration biopsy is the method of choice to establish the diagnosis. PMID- 2192082 TI - Cysts of the semilunar cartilages of the knee: a new approach by ultrasound imaging. A study of six cases and review of the literature. AB - The authors present six cases of cysts of the semilunar cartilages of the knee detected by ultrasonography, all of them confirmed at the time of surgery. Five of these lesions were cysts of the lateral meniscus; one lesion was a cyst of the medial meniscus. Because of ultrasonography, an accurate diagnosis of meniscal cysts is within the reach of the radiologist; it is also possible to visualize the extension of these lesions in a correct way, thereby being of great help to orthopedic surgeons. The main advantages of this technique compared with magnetic resonance imaging (MRI), which is also able to give the same information, are the short time required to perform the examination and the low costs. After outlining their study, the authors give a review of the literature concerning the incidence, clinical features, pathogenesis, and management of the disease. PMID- 2192083 TI - Screening spinal ultrasound in newborns with neural tube defects. AB - Twenty-six newborns with spina bifida had complete spinal ultrasound (US) prior to initial surgical repair of the neural tube defects. Associated anomalies were found on screening US in seven infants and included diastematomyelia (two cases), hydromyelia (two cases), and dural fat deposits (three cases). Initial surgical therapy was altered in one infant with diastematomyelia. Four closed simple meningoceles showed no internal neural elements on US and none were found at surgery. PMID- 2192084 TI - Duplex carotid sonography. Peak systolic velocity in quantifying internal carotid artery stenosis. AB - Duplex ultrasonography combining high-resolution imaging and Doppler spectrum analysis was performed in 92 consecutive patients (total, 180 vessels) and compared with the findings of conventional arteriography. All duplex studies were categorized into four groups based upon the maximum internal carotid artery (ICA) velocity: group 1: less than 125 cm/sec; group 2: 125 to 224 cm/sec; group 3: greater than 225 cm/sec; and group 4: no flow. Sensitivities and specificities were highest when peak ICA velocity was used as one of several criteria in quantifying the degree of ICA stenosis. These additional criteria were: (1) the presence of extensive sonographically visible plaque within the ICA; (2) an abnormal spectral waveform with elevated diastolic velocity (greater than 100 cm/sec); (3) resistive pattern ("externalization") of the common carotid artery (CCA) waveform; and (4) the ratio of the right CCA peak velocity to the left of less than 0.7 or greater than 1.3. The overall accuracy for the combined groups using all criteria was 94%. PMID- 2192085 TI - Eventration of the diaphragm. Prenatal diagnosis. PMID- 2192086 TI - Emphysematous pyelonephritis in a polycystic kidney. Demonstration by ultrasound and computed tomography. PMID- 2192087 TI - Prenatal sonographic findings in bladder exstrophy. PMID- 2192088 TI - Prenatal diagnosis of agenesis of the corpus callosum using endovaginal ultrasound. PMID- 2192089 TI - Extrauterine amniotic sac (amniocele). Clinical workup in a case of silent uterine rupture. PMID- 2192090 TI - Ethics in ultrasound. PMID- 2192091 TI - In-utero fetal penile erection. PMID- 2192092 TI - The role of data audits in detecting scientific misconduct. PMID- 2192094 TI - Work continues on extending protection against Haemophilus influenzae to very young infants. PMID- 2192093 TI - Small adenomas detected during fecal occult blood test screening for colorectal cancer. The impact of serendipity. AB - Yearly fecal occult blood testing (FOBT) has been recommended for men and women over age 50 years as part of a screening regimen intended to reduce colorectal cancer mortality. The primary targets of screening are early, surgically curable colon cancers and large adenomatous colon polyps; however, screening may sometimes reveal only small adenomas (ie, less than 1 cm in diameter). To assess the rates and mechanisms of FOBT detection of small adenomas, we performed quantitative analyses utilizing estimates of adenoma bleeding rates and FOBT sensitivity and specificity. The analysis suggests that the mechanisms of detection of small adenomas is often chance or serendipity. This occurs when an FOBT result is "falsely" positive because of diet or non-neoplastic gastrointestinal bleeding and leads to colonoscopic discovery of a nonbleeding small adenoma. Nevertheless, small adenomas remain undetected in most persons who have them, even if repeated yearly FOBT screening is done. The identification of persons with small adenomas should not be assumed to be an important beneficial outcome of FOBT screening, because the clinical significance of small adenomas is not clear, the mechanism of detection is serendipity, and only a minority of persons with small adenomas are identified. The current recommendations to perform periodic surveillance colonoscopy following removal of small adenomas detected during FOBT screening should be reexamined. PMID- 2192095 TI - From the Centers for Disease Control. Update: serologic testing for HIV-1 antibody--United States, 1988 and 1989. PMID- 2192096 TI - Sexual transmission efficiency of hepatitis B virus and human immunodeficiency virus among homosexual men. AB - The relative sexual transmission efficiency of hepatitis B virus (HBV) and human immunodeficiency virus type 1 (HIV-1) was investigated by a prospective study of homosexual men in Pittsburgh, Pa, from the Multicenter AIDS Cohort Study. During the 30-month follow-up, 19.8% and 7.8% of the initially seronegative HBV and HIV 1 groups were estimated to seroconvert to HBV and HIV-1, respectively. The significantly higher cumulative HBV seroconversion rate occurred despite a much lower prevalence of hepatitis B carriers (7% were hepatitis B surface antigen positive) compared with HIV-1 carriers (22% were HIV-1 antibody positive). The sexual exposure profile of HBV and HIV-1 seroconverters was similar during the 6 months prior to seroconversion, supporting the link between anal intercourse and acquisition of either infection. However, insertive, not receptive, anal intercourse was the major risk factor identified for HBV seroconversion, suggesting that transurethral exposure is an important mode of transmission. These data suggest that HBV is transmitted 8.6-fold more efficiently than HIV-1 among homosexual men studied and underscore the benefits of both HBV immunization and use of condoms during intercourse to prevent HBV infection. PMID- 2192097 TI - Chernobyl hero (and victim) fighting for life in American hospital. PMID- 2192098 TI - Efficacy and tolerability of long term oxprenolol and chlorthalidone singly and in combination in hypertensive blacks. AB - Sixty two black patients who had confirmed but untreated hypertension participated in a double blind clinical trial of the efficacy and tolerability of slow-release oxprenolol in a daily dose of 160 mg initially and 320 mg subsequently versus chlorthalidone 50 mg daily. Thereafter, a combination of oxprenolol with chlorthalidone in an initial dose of 160 mg and 25 mg and a subsequent dose of 320 mg and 50 mg, respectively, was administered and the effects compared with those of the same drugs given singly. The trial lasted for 3 years, but each participant took active medication for 1 year. Oxprenolol as monotherapy had no effect on the blood pressure, irrespective of the dose. Chlorthalidone as monotherapy produced a significant fall in blood pressure (p less than 0.01). Combining the 2 drugs enhanced their blood pressure lowering effects (p less than 0.001). Oxprenolol as monotherapy and as part of combination therapy was well tolerated by all patients. Chlorthalidone as monotherapy was well tolerated by most patients while a fraction of the patients developed biochemical derangements. These results confirm the findings that a beta-blocker alone may be ineffective in lowering blood pressure in hypertensive blacks. The results also show that the efficacy and tolerability of a beta-blocker and a diuretic are enhanced by their combined administration. Finally, the results show that increasing the dose of a beta-blocker or a diuretic does not produce a further increase in its blood pressure lowering effect. PMID- 2192099 TI - Double blind comparative trial of Abana and methyldopa for monotherapy of hypertension in Indian patients. AB - Abana is a herbomineral medicinal preparation with a property of down-regulation of beta-adrenergic receptors. A double-blind, parallel group study was conducted in 43 Indian men and women suffering from hypertension to evaluate the antihypertensive effect of Abana and compare it with that of methyldopa (M-DOPA). Twenty-one patients received 800 mg tds of Abana and 22 patients received 250 mg tds of M-DOPA for 4 weeks. Blood pressure and pulse rate were recorded at weekly intervals. Relevant clinical and biochemical investigations were carried out before and after treatment. In patients treated with Abana, there was a significant fall both in systolic B.P. (from 167 +/- 3.73 to 145 +/- 6.11 mmHg) and in diastolic B.P. (from 110 +/- 1.86 to 91 +/- 3.04 mmHg) at the end of 4 weeks. Similarly in patients treated with M-DOPA, systolic blood pressure was significantly reduced from 165 +/- 4.92 to 146 +/- 4.9 mmHg and diastolic blood pressure was reduced from 106 +/- 2.74 to 96 +/- 2.67 mmHg after 4 weeks. The onset of antihypertensive effect was earlier and there was a higher percentage of responders (80%) in the Abana-treated group. None of the patients had clinically or biochemically significant side-effects. The results of this study suggest that therapy with Abana proved highly effective in hypertensive patients. PMID- 2192100 TI - [An autopsy case of extramural malignant leiomyoblastoma of the stomach with ovarian cancer: an immunohistochemical study]. AB - The subject was an 85-year-old woman, who had been diagnosed as having an ovarian cancer and carcinomatous peritonitis and had been treated conservatively. She subsequently died from respiratory and renal insufficiency, and the autopsy that followed revealed that her pelvic cavity had been filled by a tumorous mass that size of a child's head. Histologically, the tumor was a serous cystadenocarcinoma of the ovary. Moreover another tumor, also the approximate size of a child's head, was found sited extramurally, beneath the posterior wall mucosa of the stomach body. Histological inspection of this tumor revealed a proliferation of round oval, and spindle-shaped tumor cells. A vacuolation of the cytoplasms and karyomitosis to the extent of 10/50 HPF also were observed. Based on the findings of being positive for Vimentin and a negative EMA, this tumor was diagnosed as being a malignant leiomyoblastoma of the stomach smooth muscle. The leioblastoma is a relatively uncommon neoplasm, and recent advances in immunohistochemical staining have indicated that some of these tumors are not only of smooth muscle derivation but also of nerve origin. Therefore, this tumor, given its morphological characteristics, had been generalized in this case as a gastric stromal tumor, and with negative findings for Desmin and S-100 protein, as well as positive for Vimentin. PMID- 2192101 TI - [Peroxisomal disorders; newer concept and recent studies]. PMID- 2192102 TI - [Identity of tRNA]. PMID- 2192103 TI - [Evaluation of KMO1 for the gastrointestinal disease]. PMID- 2192104 TI - [Clinical significance of ST 272 Ag detected by the monoclonal antibody, NCC-ST 272]. PMID- 2192105 TI - [Clinical significance of NCC-ST-439 antigen assay detected by the monoclonal antibody as a tumor marker]. PMID- 2192106 TI - [Clinical significance of SCC antigen assay as a tumor marker]. PMID- 2192107 TI - [Clinical significance of YH-206 assay analysis as a tumor marker]. PMID- 2192108 TI - [Therapeutic drug monitoring of ethosuximide]. PMID- 2192109 TI - [Therapeutic drug monitoring of carbamazepine]. PMID- 2192110 TI - [Therapeutic drug monitoring of tricyclic antidepressants]. PMID- 2192111 TI - [Kininogen analysis and the clinical significance]. PMID- 2192112 TI - [Therapeutic drug monitoring of primidone]. PMID- 2192113 TI - [Therapeutic drug monitoring of inhibitors of renin-angiotensin system]. PMID- 2192114 TI - [Therapeutic drug monitoring of digitoxin]. PMID- 2192115 TI - [Plasma and urinary kinin assay and the clinical significance]. PMID- 2192116 TI - [Therapeutic drug monitoring of procainamide]. PMID- 2192117 TI - [Therapeutic drug monitoring of salicylic acid]. PMID- 2192118 TI - [Therapeutic drug monitoring of lidocaine hydrochloride]. PMID- 2192119 TI - [Therapeutic drug monitoring of aminoglycosides]. PMID- 2192120 TI - [Therapeutic drug monitoring of antitumor agents]. PMID- 2192121 TI - [Immunological fecal occult blood test]. PMID- 2192122 TI - [Plasma pancreatic glucagon assay and the clinical significance]. PMID- 2192123 TI - [Plasma renin concentration assay and the clinical significance]. PMID- 2192124 TI - [Diagnosis of RS virus infection]. PMID- 2192125 TI - [Diagnosis of HTLV-I infection]. PMID- 2192126 TI - [Diagnosis of HIV infection]. PMID- 2192127 TI - [Plasma IRI--assay method and its significance]. PMID- 2192128 TI - [Plasma secretin assay and the clinical significance]. PMID- 2192129 TI - [Serodiagnosis of aspergillus infection]. PMID- 2192130 TI - [Serodiagnosis of Chlamydia infection]. PMID- 2192131 TI - [Serodiagnosis of entamoebiasis]. PMID- 2192132 TI - [Plasma pancreatic polypeptide assay and the clinical significance]. PMID- 2192133 TI - [Diagnosis of syphilis]. PMID- 2192134 TI - [Diagnosis of tetanus]. PMID- 2192135 TI - [Diagnosis of filariasis]. PMID- 2192136 TI - [Diagnosis of Lyme disease]. PMID- 2192137 TI - [Serodiagnosis of leprosy]. PMID- 2192138 TI - [Serologic diagnosis of rickettsial diseases--early and rapid diagnosis of great importance]. PMID- 2192139 TI - [Serodiagnosis of Legionnaires' disease]. PMID- 2192140 TI - [Clinical significance of parietal cell antibody analysis]. PMID- 2192141 TI - [Clinical significance of anti-DNA antibody]. PMID- 2192142 TI - [Plasma C-peptide assay and the clinical significance]. PMID- 2192143 TI - [Clinical significance of anti-C1q antibody]. PMID- 2192144 TI - [Clinical significance of anti-vimentin antibody assay]. PMID- 2192145 TI - [Clinical significance of anti-skeletal muscle antibody assay]. PMID- 2192146 TI - [Clinical significance of antinuclear antibody assay]. PMID- 2192147 TI - [Clinical significance of anti-thyroid microsomal antibody assay]. PMID- 2192148 TI - [Clinical significance of anti-brush border antibody assay]. PMID- 2192150 TI - [Clinical significance of antimyocardial antibody assay]. PMID- 2192149 TI - [Clinical significance of antiglomerular basement membrane antibody assay]. PMID- 2192151 TI - [Clinical significance of islet cell antibody assay]. PMID- 2192152 TI - [Clinical significance of anti-gonad antibody assay]. PMID- 2192153 TI - [Clinical significance of anticentromere antibody assay]. PMID- 2192155 TI - [Clinical significance of antiadrenocortical antibody assay]. PMID- 2192154 TI - [Clinical significance of anti-histone antibody assay]. PMID- 2192156 TI - [Clinical significance of smooth muscle antibody assay]. PMID- 2192157 TI - [Clinical significance of antimitotic spindle-associated antibody assay]. PMID- 2192158 TI - [Clinical significance of anti-mitochondrial antibody assay]. PMID- 2192159 TI - [Clinical significance of anti-reticulin antibody assay]. PMID- 2192160 TI - [Clinical significance of C3 receptors (CR1, 2, 3, 4) analysis]. PMID- 2192161 TI - [Clinical significance of C1q binding assay]. PMID- 2192162 TI - [Plasma sex hormone binding globulin assay and the clinical significance]. PMID- 2192163 TI - [Clinical significance of C3.R+ cell count]. PMID- 2192164 TI - [Plasma angiotensin I assay and the clinical significance]. PMID- 2192165 TI - [Clinical significance of interleukin-3 analysis]. PMID- 2192166 TI - [Anti-bovine or porcine-insulin antibody]. PMID- 2192168 TI - [Clinical significance of anti-deoxyribonuclease B assay]. PMID- 2192167 TI - [Clinical significance of the ASK test]. PMID- 2192169 TI - [Clinical significance of anti-hyaluronidase antibody]. PMID- 2192170 TI - [Biological and pharmacological activity of tumor necrosis factor and clinical significance of the assay]. PMID- 2192171 TI - [Clinical significance of heterophile antibody assay]. PMID- 2192172 TI - [Clinical significance of isoferritin assay as a tumor marker]. PMID- 2192173 TI - [Clinical significance of carcinoembryonic antigen assay as a tumor marker]. PMID- 2192174 TI - [Clinical significance of pancreatic oncofetal antigen, pancreatic cancer associated antigen assay as tumor markers]. PMID- 2192175 TI - [Clinical significance of gamma-seminoprotein assay as a tumor marker]. PMID- 2192176 TI - [Plasma osteocalcin assay and the clinical significance]. PMID- 2192177 TI - [Clinical significance of carbohydrate antigen 19-9 assay as a tumor marker]. PMID- 2192178 TI - [Clinical significance of anti human N-myc protein antibody assay as a tumor marker]. PMID- 2192179 TI - [Urinary fibronectin of cancer patients detected by monoclonal antibody]. PMID- 2192180 TI - [Clinical significance of beta 2-microglobulin assay as a tumor marker]. PMID- 2192181 TI - [Monoclonal antibody A2B5--its clinical application for diagnosis of APUD tumors]. PMID- 2192182 TI - [Clinical significance of CA 50 assay as a tumor marker]. PMID- 2192183 TI - [Clinical significance of CA125 assay as a tumor marker]. PMID- 2192184 TI - [Effect of cepharanthin on radiotherapy induced leukopenia]. AB - Cepharanthin, a kind of alkaloid, has been reported to show a protective effect for leukopenia induced by radiation therapy. In this study, one of three kinds of drugs, Cepharanthin, S-Adchnon (adrenochrome derivative) and Hythiol (L cysteine), was randomly administered to 94 patients with cancer of the head and neck, the uterine cervix and the lung, during the course of radiotherapy. When Cepharanthin was given, 81.3% of the patients were protected from leukopenia, compared with 51.6% in S-Adchnon and 32.3% in Hythiol. It is suggested that prophylactic use of Cepharanthin may be useful for cancer radiotherapy. PMID- 2192186 TI - Intrarenal reflux and nephropathy. AB - Using anti-Tamm-Horsfall protein (THP) immunohistochemical study was performed to analyse the relationship between intrarenal reflux and induced nephropathy in surgically resected kidney tissues including hydronephrosis, renal calculi and trauma. With the increase of the histological grade of hydronephrosis intrarenal reflux was observed in two ways. Extra-tubular efflux of THP was seen to correlate with mononuclear and lymphocytic interstitial inflammation with the initiation by cellular immune response. The reflux of THP was also observed in the Bowman's space, but this did not seem to result in glomerular lesions including adhesion and/or sclerosis. PMID- 2192185 TI - [Mesenteric hematoma; a pediatric case]. AB - A 3-Year-old girl was admitted to National Beppu Hospital due to abdominal mass. US examination revealed cystic mass with multiple scattered nonreverberatory echoes in right upper abdomen. CT examination revealed almost homogeneous mass (29-31 H.U.) with a few internal components (36-42 H.U.). US and CT were useful methods for diagnosis of mesenteric hematoma. PMID- 2192188 TI - [Interaction of swallowing and control of breathing]. AB - Although it is well known that swallowing interacts with respiration, information about the relationship between respiration and swallowing is limited. In this paper we described the interaction between swallowing reflex and respiration. In experimental animals, reflex swallowing can be elicited readily by electrical stimulation of the superior laryngeal nerve, and the effects of depressants on this reflex can be assessed by changes in the latency of responses and the number of swallows elicited. The swallowing reflex is independent of the background respiratory activity and a decrease in PaO2 depresses the swallowing reflex, whereas changes in Paco2 have no effect. In human subjects, the swallowing reflex can be induced by injections of a small amount of water into the pharynx. Like the responses in animals, the responses in humans can be assessed by changes in the latency of responses and the number of swallows. Using this technique, we evaluated the effects of nasal CPAP on the swallowing reflex. Our results showed that nasal CPAP remarkably depresses the swallowing reflex. PMID- 2192187 TI - [Thromboxane A2 could be involved in bronchial hyperresponsiveness to methacholine in asthmatic subjects but not in bronchitic subjects]. AB - To determine whether the involvement of thromboxane A2 in bronchial hyperresponsiveness is specific to asthma, we examined the effects of a selective thromboxane synthetase inhibitor (OKY-046) and a cyclooxygenase inhibitor (indomethacin) on bronchial responsiveness to methacholine in patients with bronchial asthma and chronic bronchitis. The provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20 FEV1) was measured before and after oral administration of OKY-046 and indomethacin in eight asthmatic and 10 bronchitic subjects. Baseline FEV1 value was not altered by OKY-046 or indomethacin. The geometric mean value of PC20-FEV1 increased significantly (p less than 0.005) from 1.78 to 4.27 mg/ml after OKY-046 in asthmatic subjects, but not in bronchitic subjects. On the other hand, PC20 FEV1 was not altered by indomethacin in all subjects. It was concluded that the involvement of thromboxane A2 in bronchial hyperresponsiveness may be specific to asthma. PMID- 2192189 TI - [Extrapulmonary lesions of sarcoidosis]. AB - Varieties of extrapulmonary sarcoidosis lesions have been detected in Japan, mostly in the past ten years, including heart, CNS, liver, spleen, bone marrow stomach, colon, esophagus, pancreas, gall bladder, abdominal lymph node, kidney, muscle, bone, joint and others. Most of these were detected mainly at onset with sarcoid changes on chest film. Hepatic lesions have frequently been found by peritoneoscopy and liver biopsy, irrespective of the age of patients or stage of sarcoid change on chest film. Therefore hepatic lesions are very important in the diagnosis and following the clinical course of sarcoidosis. Recent diagnostic procedures of extrapulmonary lesion include abdominal, cardiac and muscle echography; brain, chest, abdominal and muscle CT; cardiac and muscle MRI; gallium scan; thallium myocardial scan, cardiac pool scan and Holter ECG. Extrapulmonary sarcoidosis lesions causing disability were located in the heart, CNS, eye, liver, kidney, muscle and bone. These disabilities were found predominantly in cases older than 40 years old, and were mainly detected at onset in the past 10 years. The duration of some of these disabilities was more than 10 years. PMID- 2192190 TI - [Utility of clinical examinations and anti-Kveim monoclonal antibody in the diagnosis of sarcoidosis]. AB - The most reliable method for a diagnosis of sarcoidosis is histological examinations. However, compatible histological findings were detected among 60% of cases and 40% of cases was diagnosed by clinical evidence only (Clinical sarcoidosis). We assessed the diagnostic reliability of the cases based on clinical features only with a comparison of positivity between definite and clinical sarcoidosis for different clinical examinations. Chest X-ray, ACE, PPD skin test etc., % positivity of BHL, ACE, PPD skin test and 67Ga scan were positive in more than 80% of definite cases but only 50% in clinical cases except for 67Ga scan. This finding means that it is necessary to develop new clinical laboratory methods to diagnose clinical sarcoidosis. From these points of view, we prepared a monoclonal antibody (IHY-1) to the sarcoid granulomagenic agent contained in Kveim suspension by immunizing mice with Kveim suspension. IHY-1 is an IgM monoclonal antibody that did not react with erythrocytes, lymphocytes, monocytes, alveolar macrophages or macrophage derived cell lines. It reacted with granuloma epithelioid cells of sarcoidosis-affected lymph nodes. Also in the granuloma of cases accompanied by tuberculosis, the monoclonal antibody positively reacted with epithelioid cells although the reaction was not strong. PMID- 2192191 TI - [Symptoms and diagnosis of tumors of the central nervous system in children]. AB - Prognosis of brain tumors in children is altogether bad. For this reason it is necessary to diagnose brain tumors earlier as yet to improve the outcome. Symptoms of intracranial space occupying lesions are at first ambiguous: vomiting and headache, frequently associated with changes of behavior. Complaints of patients with brain tumors are multiple and progressive, in contradiction to patients suffering from spinal tumors showing only vague symptoms for a long time. Modern neuroimaging techniques such as sonography, computed tomography (CT) and nuclear magnetic resonance tomography (NMR) should be used early in patients with suspected symptoms. PMID- 2192192 TI - [Post-traumatic pancreatic pseudocyst in children]. AB - This is a report on a posttraumatic pancreas-pseudocyst of a six year old girl. The fast grow of this pancreatic pseudocyst demanded the surgical intervention in form of the cystogastrostomia. The most important factor for the decision for the operation was the sonographic imagic. PMID- 2192193 TI - Insulin secretion and carbohydrate tolerance in childhood obesity. AB - The inability to clear glucose adequately from the blood is a common feature of obesity. The frequency of impaired glucose tolerance has been reported to vary from 11.5% to 74% on obese children: the causes of this discrepancy in the literature are discussed. Carbohydrate intolerance occurs in obesity in spite of the basal and reactive hyperinsulinaemia. This condition is termed insulin resistance, which can develop in several ways. The different theories concerning the primary cause or causes of insulin resistance in obesity are reviewed. PMID- 2192194 TI - Symptoms of hypoglycemia--a comparison between porcine and human insulin. AB - For more than 2 years now it has been controversially debated whether awareness of hypoglycemia is reduced when type I diabetic patients are switched from porcine to human insulin. In order to address this question, we studied nine C peptide negative diabetics (age 27.6 years, Broca index 106%, duration of diabetes 5.7 years, HbA1, 8.8%) in comparison with eight healthy volunteers (age 22.4 years, Broca index 104%). Following euglycemic monitoring overnight, a controlled hypoglycemia was induced by altering the algorithms of the Biostator. This was done in a double-blind, cross-over fashion using porcine or human insulin on 2 nonconsecutive days. There were no differences between the results obtained with respect to the time course of the study, blood glucose, amount of insulin infused, and concentration of venous free insulin achieved. Of the nine diabetics, eight were aware of hypoglycemia at a higher blood glucose level under porcine insulin. The first symptom of hypoglycemia was perceived at a mean blood glucose level of 61.1 +/- 5.4 mg/dl under porcine insulin and of 44.4 +/- 5.3 mg/dl under human insulin (P less than or equal to 0.05). Thirty symptoms were noted under porcine insulin exclusively or preferentially as opposed to only eight which were observed exclusively or preferentially under human insulin. The healthy volunteers evidenced fewer symptoms at lower blood glucose concentrations than the diabetics. The clear difference between human and porcine insulin could not unequivocally be reproduced in this group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2192195 TI - Prospective application of an expert system for the medical history of joint pain. AB - An expert system with 60 questions about medical history was developed for 32 rheumatologic diseases: 358 outpatients with joint complaints have been examined. The final diagnosis (result of symptoms, signs, and findings) was compared with the computer diagnoses and with the independently assumed diagnoses of the physician. The only source of information available to the physician was the medical history. Misinterpretation of the computer diagnoses occurred in 25.6% of cases compared with 21.5% of the physician. The final clinical diagnosis remained uncertain in 32.6% of cases. The error frequency of the expert system was influenced by the underlying disease, the certainty of the assumed diagnosis by the physician, the user experience in rheumatology, the number of questions asked, and the time of application before or after the doctor-patient contact. Of the errors 44% were produced because of information deficits of the computer using standardized questions. The information of the physician in the diagnostic process is quite different to that of the computer. PMID- 2192196 TI - Specific steroid-binding glycoproteins of human blood plasma: novel data on their structure and function. PMID- 2192197 TI - Central venous catheter complications in sarcoma patients receiving adjuvant chemotherapy. AB - As part of a prospective randomized study in patients with high grade soft tissue sarcoma (STS), 47 patients received post-operative adjuvant Adriamycin. The method of administration was randomized to intravenous bolus (B) or to continuous 72 hour infusion (CI) via a Silastic right atrial catheter. Both groups received 60 mg/m2 every 3 weeks. There were nine hospital admissions for treatment related complications in four of the 26 CI patients compared to none in the 21 B patients (P = 0.03). All of the admissions related to complications involving the central venous catheter (CVC). This apparent increased risk for hospital admission secondary to treatment related complications in patients treated with CI must be considered in the planning of future therapeutic trials. PMID- 2192198 TI - Technical efficiency in nursing homes. PMID- 2192199 TI - [Heatstroke]. PMID- 2192200 TI - [Consensus agreement on controlling blood cholesterol in Spain]. PMID- 2192201 TI - [Thrombocytopenia after bone marrow transplant]. PMID- 2192202 TI - [Etiology of late-onset epilepsy. A prospective study in an area of rural health care]. AB - A prospective study of 3 years' duration on the etiology of late onset epilepsy was carried out in a rural health area with a population of 135,000. Eighty patients were included. History, neurological physical examination, electroencephalogram, cranial computed tomographic scan (CT) and general laboratory investigations were carried out. The cause of epilepsy was unknown in 51.3% of cases. The most commonly identified causes were cerebrovascular disease (20%), chronic alcohol abuse (10%), tumors of central nervous system (6.3%), neurocysticercosis (6.3%) and post-traumatic epilepsy (2.5%). Our data are compared with those from the previous literature, and the value of cranial CT in the investigation of this clinical condition is discussed. PMID- 2192203 TI - [What factors make the diagnosis of pulmonary thromboembolism difficult?]. AB - A series of 63 cases of fatal acute pulmonary thromboembolism (PTE) with available necropsy study was evaluated The diagnosis was established ante mortem in 20 cases (predictive index 31%). The diagnosis was only suspected in 2 of the 16 patients in whom PTE was associated with pneumonia (predictive index 12.5%, p less than 0.01), in 3 of the 26 cases if PTE associated with neoplasia (predictive index 11.5% p less than 0.01) and in 8 of the 41 cases with terminal disease (predictive index 19.5%, p less than 0.01). On the contrary, thrombophlebitis and relapsing PTE had a significative facilitation effect on the diagnosis (predictive indexes 53.3% and 52.6%, respectively; p less than 0.01). It was concluded that the presence of neoplasia, pneumonia or terminal illness make the diagnosis of pulmonary thromboembolism difficult. PMID- 2192204 TI - [Late-onset epilepsy]. PMID- 2192205 TI - [Infantile exanthematous virosis in adults]. PMID- 2192206 TI - [Arthritis caused by Streptobacillus moniliformis: a case of fever induced by a rat bite]. AB - A 54-year-old female had fever with chills, polyarthritis and diffuse rash. Anamnesis led to the suspicion of rat-bite fever. The etiology was confirmed when and organism which was identified as Streptobacillus moniliformis was isolated from articular fluid by means of gas chromatography of tissue fatty acids. In our opinion, this is the first case of that condition reported in this country. We review the literature, and we insist on the need to inform the microbiologist of the clinical suspicion to achieve the etiological diagnosis. PMID- 2192208 TI - [Infections caused by bacteria of the Campylobacter genus]. PMID- 2192207 TI - [A 38-year-old male with abdominal pain, fever and bloody diarrhea]. PMID- 2192209 TI - [Treatment with cyclosporin in the pregnant woman with a kidney transplant]. PMID- 2192210 TI - [An experimental model of Parkinson disease caused by a neurotoxin: implications in the clinical aspects and the etiology of Parkinson disease]. PMID- 2192211 TI - [Importance of bronchial hyperreactivity in cough induced by captopril]. PMID- 2192212 TI - [En bloc esophagectomy--when should the digestive tract be reconstructed?]. AB - In a prospective study direct reconstruction of the esophagus was compared to reconstruction 48-72 h after esophagectomy. In both groups (26/24) transthoracic en-bloc esophagectomy was performed. During the same time period of the study another group of 45 patients had transmediastinal esophagectomy and direct reconstruction and this group was also used as comparison. There were no differences concerning postoperative complications (26.9%; 29.1%; 22.2%), postoperative 30-days mortality (0%; 4.1%; 2.1%), and hospital mortality (3.2%; 4.1%; 4.2%). Thus reconstruction with delayed urgency does not lead to a further decrease of risk; on the other hand there is also no increase of risk and therefore it can be included in the spectrum of procedures of esophageal surgery. PMID- 2192213 TI - Sutureless colonic anastomoses. PMID- 2192214 TI - Effect of angiotensin II on angiotensinogen production in adrenalectomized rats. AB - The present study was performed to examine the effect of angiotensin II on hepatic angiotensinogen production in adrenalectomized rats. The hepatic angiotensinogen mRNA levels in rats without adrenal glands increased 2.8-fold 4 h after the start of angiotensin II infusion. In intact rats with adrenal glands, the hepatic angiotensinogen mRNA levels increased 2.7-fold 4 h after the start. The angiotensin II infusions did not only increase angiotensinogen mRNA levels in intact rats but also increased those in adrenalectomized rats. The results suggest that the angiotensinogen response to ANG II was not dependent on adrenal glucocorticoid. PMID- 2192215 TI - Neuroendocrine control of thymic hormonal production. II. Stimulatory effects of endogenous opioids on thymulin production by cultured human and murine thymic epithelial cells. AB - Data have now accumulated to strongly demonstrate that several neuropeptides, including endogenous opioids, can have immunomodulatory functions. Most of the studies have so far focused on the direct action of these substances on lymphocytes. We decided to investigate whether thymic epithelial cells (TEC) - the major component of the thymic microenvironment - could also be modulated by endogenous opioids. Primary cultures of human and murine TEC were subjected to several opioids (alpha-beta- or gamma-endorphins, as well as met- or leuenkephalins) applied in concentrations ranging from 10(-6) to 10(-9) M. On the following days we measured the levels of thymulin (a chemically-defined thymic hormone known to stimulate some steps of T-cell differentiation) in the culture supernatants, as well as the numbers of thymulin containing cells, evaluated by immunofluorescence with an anti-thymulin monoclonal antibody. After treatment of TEC cultures with beta-endorphin or leu-enkephalin a significant increase in the levels of thymulin in the culture media was observed, paralleled by a rise in the percentage of thymulin containing cells. In addition, this stimulatory effect was dose-dependent. Preincubation of the opioids with the specific antibodies abrogated the opioid-induced stimulatory effect on TEC. Moreover, naloxone, an opioid receptor antagonist, blocked the effect of beta-endorphin on thymulin production, suggesting that the effect of this neuropeptide on epithelial cells was mediated by an opioid receptor. Importantly, no effect on thymulin production was observed with the other opioids used, whatever the dose. These results suggest that, at least in vitro, beta-endorphin and leu-enkephalin stimulate the hormonal function of the thymic epithelium. These findings lead to the general concept that the modulatory role of endogenous opioids on the immune system is not restricted to lymphocytes but can also take place at the level of cells belonging to T-cell differentiating microenvironments. PMID- 2192216 TI - [Potential for ultrasonic diagnosis in determining the nature of a bulky lesion of the liver]. AB - Ultrasound investigation (USI) of the liver was performed in 6570 patients, focal lesions were detected in 80 (1.2%). Of them 53 patients (66.2%) had a benign process, 27 (33.8%)--a malignant process. Four variants of focal pathology with its specific nature were singled out on the basis of analysis of the echo structure. Anechogenic foci reflected a cystic process, foci of mixed echo density--malignant lesions (a metastasis, liver cancer). The determination of the nature of echo-dense and low echogenic foci is the most complex problem of USI. In most cases echo-dense foci reflected benign liver tumors (7:1). USI in 56.3% of patients permitted the recognition of the nature of a sizable liver tumor without resorting to other radiation-methods; in another one-third of patients- during dynamic observation. PMID- 2192217 TI - [Ultrasonic diagnosis in arthrology]. PMID- 2192218 TI - [Changes of the thyroid under the influence of irradiation]. PMID- 2192219 TI - [Surgical, radiation and drug treatment of breast cancer]. PMID- 2192220 TI - [Radionuclide methods of assessing the functional state of the reticuloendothelial system]. PMID- 2192221 TI - J.B. Wolffe memorial lecture. Neural control of the circulation during exercise. PMID- 2192222 TI - Hepatic lipid metabolism in exercise and training. AB - The liver plays a central role in the metabolism of fat. The available data, though sometimes controversial, clearly indicate that muscular exercise affects almost every aspect of fat metabolism in this organ. Neither acute exercise nor training affects total lipid, phospholipid, or cholesterol concentrations in the liver of rats fed chow or low fat diets. However, exercise training reduces accumulation of total hepatic fat and cholesterol in rats fed a fat-rich diet. In addition, training seems to increase both the synthesis and catabolism of cholesterol in the liver in rats fed a chow diet. Production of ketones by the liver increases both during prolonged exercise and during recovery from exercise. Acute prolonged exercise reduces the activities of the enzymes involved in the synthesis of fatty acids and increases oxidation of fatty acids by the liver. This type of work also increases the esterification of fatty acids with the subsequent accumulation of triacylglycerols in this organ. Training does not affect triacylglycerol concentration in the liver of rats fed a chow diet but attenuates its accumulation after a fat-rich diet. Training reduces the postheparin plasma hepatic lipase activity. Finally, it reduces production of triacylglycerols and increases production of high density lipoprotein cholesterol by the liver. A large body of descriptive information has been published indicating that exercise has a dramatic effect upon hepatic lipid metabolism. The next step in this work is the identification of the molecular mechanisms responsible for these exercise-induced alterations. PMID- 2192223 TI - Historical significance on rat organ transplantation. PMID- 2192224 TI - Development and perspectives of experimental pancreas transplantation in the rat. AB - Whole organ pancreas transplantation in the rat was first described by Sun Lee in 1972. Since that time the basic technique has been modified in several ways and this model can now be used for a variety of experiments. Various techniques for transplantation and representative results of functional and immunological experiments are summarized. PMID- 2192225 TI - Metabolic effect of pancreas transplantation on long-term diabetic rats. AB - Thirty-six male Lewis rats rendered diabetic using alloxan received syngeneic pancreaticoduodenal grafts. Seven days prior to and 7, 30, and 90 days posttransplantation, the animals were housed in metabolic cages for periods of 48 hours. During this time, body weight, water intake, food intake, urine output, and fecal output were recorded every 24 hours. Blood sugar, plasma insulin, glucosuria, and proteinuria were determined at 3-month intervals prior to the transplant and at monthly intervals posttransplantation. These parameters were also concurrently recorded for diabetic control rats. Pancreaticoduodenal transplantation produces immediate relief of hyperglycemia, glucosuria, polyuria, polyphasia, and polydypsia, resulting in good health of the animals until the time of sacrifice. A significantly increased insulin level was also recorded. The transplanted animals showed a weight gain reflecting that of a normal growth curve. PMID- 2192226 TI - Experience in rat pancreas transplantation at Meikai University. AB - A review of rat pancreatic transplantation conducted at Meikai University is presented. It was found that pancreas transplantation normalized the endocrine based metabolic disturbances of diabetes. Arginine-induced serum insulin, glucagon, and somatostatin responses in the grafted pancreas were similar to those in normal pancreas. Urine amylase was found to be a more sensitive marker in graft rejection as compared with blood glucose using a urinary drainage model. The value of pancreas transplantation in diabetic nephropathy was dependent upon the timing of the transplantation; performed early in the course of diabetes (less than 4 months, post-diabetes), it was able to reverse the nephropathy. PMID- 2192228 TI - Aging and senescence of the budding yeast Saccharomyces cerevisiae. AB - The budding yeast Saccharomyces cerevisiae has a limited life span, defined by the number of times an individual cell divides. Longevity in this organism involves a genetic component. Several morphological and physiological changes are associated with yeast aging and senescence. One of these, an increase in generation time with age, provides a 'biomarker' for the aging process. This increase in generation time has revealed the operation of a 'senescence factor(s)', which is likely to be a product of age-specific gene expression. The Cell Spiral Model indicates coordination of successive cell cycles to be inherent in the determination of life span. It is proposed that life expectancy depends on the function of a stochastic trigger during aging that sets in motion a programme leading to cell senescence and death. PMID- 2192227 TI - Cis- and trans-acting factors involved in centromere function in Saccharomyces cerevisiae. AB - The function of centromeric DNA in the yeast Saccharomyces cerevisiae has been studied in detail. Twelve of the sixteen S. cerevisiae centromeres have been sequenced to date, and a consensus sequence has been identified. This sequence consists of a central region 78 to 86bp in length which is greater than 90% A + T, usually in runs of As and runs of Ts. The central region is flanked on one side by a highly conserved 8bp sequence and on the other side by a highly conserved 25bp sequence which contains partial dyad symmetry around a central C/G base pair. Mutational analyses have been used to determine the importance of each subset of the consensus sequence to centromere function. A protein which binds to the 8bp sequence and at least one that binds to the 25bp sequence have been identified. The roles of these proteins in centromere function in mitosis and meiosis are currently under investigation. PMID- 2192229 TI - Transcriptional analysis of the gene encoding pyruvate formate-lyase-activating enzyme of Escherichia coli. AB - The act gene of Escherichia coli encodes the pyruvate formate-lyase-activating enzyme which is necessary for the post-translational modification of pyruvate formate-lyase. The gene is located 191 bp downstream from the pfl structural gene. Northern blot analysis revealed that the act transcript is monocistronic and that transcription is independent of pfl gene expression. Through mapping of the 5' and 3' ends of the act transcript, sequences could be identified showing similarity to both an Escherichia coli sigma 70 promoter and to a rho-independent transcription terminator. Expression of the act gene was analysed with the aid of chromosomally integrated transcriptional and translational lacZ fusions. The results verified that the act gene is transcribed from its own promoter and that expression of the gene is essentially constitutive. Anaerobiosis led only to a two-fold increase in expression over that observed in aerobically grown cells and this elevated expression was independent of the transcriptional regulator, Fnr. Moreover, effectors such as pyruvate and nitrate, which substantially influence anaerobic transcription of the pfl gene, did not affect act gene expression. PMID- 2192230 TI - Purine biosynthesis in Escherichia coli K12: structure and DNA sequence studies of the purHD locus. AB - The de novo purine biosynthetic enzymes 5-amino-4-imidazolecarboxamide ribonucleotide (AICAR) transformylase (EC 2.1.2.3), IMP cyclohydrolase (EC 3.5.4.10) and glycineamide-ribonucleotide (GAR) synthetase (EC 2.1.2.2) are encoded by the purHD locus of Escherichia coli. The DNA sequence of this locus revealed two open reading frames encoding polypeptides of Mr 57,335 and 45,945 (GAR synthetase), respectively, that formed an operon. The DNA sequence, maxicell and complementation analyses all supported the concept that the Mr 57,335 polypeptide is the product of the purH gene and encodes a bifunctional protein containing both AICAR transformylase and IMP cyclohydrolase activities. The 5' end of the purHD mRNA was determined by primer extension mapping and contains two regions of dyad symmetry capable of forming 'hairpin' loops where the formation of the one would prevent the formation of the other but not vice versa. Regulation by the purR gene product was explained by the discovery of a purR binding site in the purHD control region. PMID- 2192231 TI - Activation of potassium efflux from Escherichia coli by glutathione metabolites. AB - The mechanism by which N-ethylmaleimide (NEM) elicits potassium efflux from Escherichia coli has been investigated. The critical factor is the formation of specific glutathione metabolites that activate transport systems encoded by the kefB and kefC gene products. Formation of N-ethyl-succinimido-S-glutathione (ESG) leads to the activation of potassium efflux via these transport systems. The addition of dithiothreitol and other reducing agents to cells reverses this process by causing the breakdown of ESG and thus removing the activator of the systems. Chlorodinitrobenzene, p-chloromercuribenzoate and phenylmaleimide provoke similar effects to NEM. lodoacetate, which leads to the formation of S carboxymethyl-glutathione, does not activate the systems but does prevent the action of NEM. It is concluded that the KefB and KefC systems are gated by glutathione metabolites and that the degree to which they are activated is dependent upon the nature of the substituent on the sulphydryl group. PMID- 2192232 TI - Identification of a 180 kD protein in Escherichia coli related to a yeast heavy chain myosin. AB - A high molecular-weight protein from Escherichia coli sharing structural homology at the protein level with a yeast heavy-chain myosin encoded by the MYO1 gene is described. This 180 kD protein (180-HMP) can be enriched in cell fractions following the procedure normally utilized for the purification of non-muscle myosins. In Western blots this protein cross-reacts with a monoclonal antibody against yeast heavy-chain myosin. Moreover, antibodies raised against the 180 kD protein cross-react with the yeast myosin and with a myosin heavy chain from chicken. Recognition by anti-180-HMP antibodies of an overexpressed fragment of yeast myosin encoded by MYO1 allows the localization of one of the shared epitopes to a specific region around the ATP binding site of the yeast myosin heavy chain. The existence of a high molecular-weight protein with structural similarity to myosin in E. coli raises the possibility that such a protein might generate the force required for movement in processes such as nucleoid segregation and cell division. PMID- 2192234 TI - The intrathecal immune response in multiple sclerosis: a different concept of 'specificity'. AB - A hypothesis is presented in which the immune response in multiple sclerosis is conceived as a primary response to an auto-antigen located within the immune system (e.g. a certain allotype or HLA epitope) which shows subsequent or simultaneous specificity for a greater number of nominal antigens [corrected]. The increased tendency of [corrected] such antibodies to self-aggregation might play a critical role in the pathogenesis. PMID- 2192233 TI - A feature model of immediate memory. AB - A feature model of immediate memory is presented, and simulations are described. List items are characterized as multiattribute vectors that can be selectively overwritten by subsequent external events and by the ongoing stream of internal activity. Degraded primary memory vectors are compared with intact secondary memory vectors, and retrieval likelihood is computed as the ratio of similarities. The model is shown to account for the major modality-based phenomena of the immediate serial recall literature, including modality-based temporal grouping effects and the negative effects of phonological similarity. PMID- 2192235 TI - Frameworks for conceptual evolution in biomedicine. AB - While biological evolution is a well-defined and accepted phenomenon, the notion of conceptual evolution, however implicit in biomedical progress, remains less well-defined and accepted. Frameworks are provided which portray conceptual evolution in terms of the spatio-temporal and hierarchical cognitive embrace of the human external and internal environments. PMID- 2192236 TI - Dietary calcium and chronic diseases. AB - The Agricultural Revolution was almost certainly associated with a substantial decrease in human calcium intake. Calcium intakes typical of contemporary humans may well be inadequate for many individuals. Various slowly developing chronic disorders such as osteoporosis, hypertension, hyperlipidemia, and colon cancer may be induced or exaggerated by the current low level of dietary calcium intake in Western societies. We propose two hypotheses relating calcium intake to diverse diseases: first, the adaptation required to adjust to low intakes is inadequate to maintain critical components of cellular calcium regulation; second, the constant, forced adaptive response to low intake itself produces untoward consequences. PMID- 2192237 TI - A proposed relationship between vasopressinase altered vasopressin and preeclampsia. AB - Preeclampsia is characterized by increased vascular sensitivity to Angiotensin II, endothelial damage, and arteriolar spasm. We hypothesize that these events may be initiated by stimulation of V1 receptors. V1 receptors are normally activated by vasopressin. However, V1 receptors may be activated by the nonapeptide formed when vasopressin is metabolized by the placental enzyme- vasopressinase. This enzyme, found only in humans, cleaves the ring structure of vasopressin, but leaves the N-terminal end, the locus of pressor activity, intact. The resulting molecule, vasopressinase altered vasopressin (VAV), may be present in greater concentration in preeclamptic women and over the months of the second trimester initiate the cascade of pathophysiologic changes resulting in toxemia. PMID- 2192238 TI - Carcinogenic implications of the neighborhood coherence principle (NCP). AB - A new hypothesis on carcinogenesis is set forth on the basis of the neighborhood coherence principle (NCP). NCP constitutes a general rule of pattern formation and maintenance. According to this principle, a system of interacting cells can produce and maintain a spatial organization by virtue of cell-cell communication. This hypothesis suggests that this homeostasis primarily results from a NCP-like process implying cell-cell communication. Each cell is constrained by its neighbors to maintain the mature phenotype despite its inherent individual variability. If the cell-cell mature communication happens to be impaired, tissue homeostasis is disrupted and a proliferative state can be initiated. A further potential effect may result from the establishment of NCP-like communication specific for proliferative cells allied to paracrine and outocrine factors which can lock the cells into the proliferative mode. Most mechanisms implied in this hypothesis have already been investigated. There is a large body of experimental results supporting the role of junctional communication in cooperative metabolism, growth, differentiation and tumour-related events. This new hypothesis provides a framework within which these known facts may be put in a theoretical perspective; it might well constitute the unifying theory--as yet missing--in carcinogenesis. PMID- 2192239 TI - Do the pancreatic primordial buds in embryogenesis have the potential to produce all pancreatic endocrine cells? AB - A heterogeneity in the cellular composition of the endocrine pancreas, with a preponderance of pancreatic polypeptide cells in the lower head region, has been linked to the dual origin of the organ. The pancreas develops from a ventral bud thought to contain potential pancreatic polypeptide cells and a dorsal bud contributing the non pancreatic polypeptide cells. This does not explain, however, several anomalies including the results reported here of a homogenous distribution of non insulin cells in the foetal baboon whilst the adult pancreas exhibits a heterogenous distribution with the pancreatic polypeptide-rich area in the lower head of the pancreas. If this heterogeneity is associated with the dual origin of the pancreas, it would be expected to be more pronounced in the foetus. The anomalies could be explained if both primordial buds contained progenitor cells of all endocrine cell types which could be expressed to meet the requirements of the body at any particular time. PMID- 2192240 TI - The aetiology of premenstrual syndrome is with the progesterone receptors. AB - Recent work by molecular biologists into the behaviour of progesterone receptors (PR) has suggested an aetiological hypothesis for premenstrual syndrome (PMS). The proposition is that PMS is related to the transport by PR of sufficient progesterone (P) molecules into the cell nuclei during menstruating years. PR are widely distributed in target cells throughout the body (1, 2, 3, 4, 5, 6, 7). It suggests also why measuring P blood levels is of no value in PMS (8, 9, 10, 11); why pharmacological doses of P are required (8); and explains the failure of current double blind trials using low dose P (12, 13, 14, 15, 16). PMID- 2192241 TI - [Therapeutic drugs--rarely causal therapy]. PMID- 2192243 TI - [Varicose veins. Compression treatment, drug therapy, sclerotherapy and surgical measures]. PMID- 2192244 TI - [Drug-induced disorders of smell]. PMID- 2192245 TI - [AIDS. Therapeutic approaches in the control of HIV infection]. PMID- 2192242 TI - [Erythropoietin]. PMID- 2192246 TI - Role of membrane phospholipids and glycolipids in the Vero cell surface receptor for rubella virus. AB - Membrane receptors for rubella virus (RV) in Vero cells were studied by means of two different approaches: (i) by enzyme treatment of the whole cell membrane and (ii) by testing the ability of isolated plasma membrane molecules to compete with cells for virus binding. The replication of RV was studied with both indirect immunofluorescence assay and molecular hybridization techniques. Phospholipases A2 and C digestion of cells greatly reduced the infectivity by the virus, pointing towards the involvement of lipid structures as receptor sites for RV. Furthermore, susceptibility of Vero cells to virus infection was also reduced after beta-N-acetyl-D-glucosaminidase, alpha-glucosidase and beta-galactosidase treatment, suggesting that carbohydrate residues may participate in a complex cellular receptor structure for RV. When the major membrane lipids were examined separately for their ability to inhibit viral infectivity, several phospholipids (phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, phosphatidylcholine, sphingomyelin) and glycolipids (gangliosides, lactosylceramide, cerebroside sulphate) showed a strong neutralizing activity, confirming the role of membrane lipid moiety in the cell surface receptor for RV. PMID- 2192248 TI - Histiocytosis X in bone only. PMID- 2192247 TI - Heat-shock proteins: a missing link in the host-parasite relationship? PMID- 2192249 TI - [Acute respiratory distress syndrome of adults. I: pathophysiology and clinical aspects]. PMID- 2192250 TI - [Clinical profile of acemetacin]. PMID- 2192251 TI - [Heart rhythm disorders in endoscopic examinations. Report of a case with asystole and literature review]. PMID- 2192252 TI - Organized medicine and the Doctors Mayo. PMID- 2192253 TI - The metaphor expert testifies on health care. PMID- 2192254 TI - Nurse practitioners to be reimbursed by Medicaid. Interview by Betty Dickson. PMID- 2192255 TI - Expression of a proteolipid gene from a high-copy-number plasmid confers trifluoperazine resistance to Saccharomyces cerevisiae. AB - A wild-type haploid yeast strain was transformed with a library of wild-type yeast DNA fragments ligated into a high-copy-number plasmid vector (YEp24). The pooled URA+ transformants were plated on rich medium containing a lethal concentration of trifluoperazine (TFP). Plasmids rescued into Escherichia coli from TFP-resistant yeast colonies contained overlapping DNA fragments from a unique region of yeast chromosome XVI. Deletion and disruption experiments, mini Tn10 LUK hop analysis, and DNA sequencing defined a novel gene with significant amino acid identity to bovine and yeast vacuoletype proteolipid subunits. This is the second locus identified that can be altered to confer TFP resistance to Saccharomyces cerevisiae and that has significant amino acid identity to a vacuolar ATPase subunit. This suggests that a target for TFP in S. cerevisiae is the electrogenic membranes of the vacuolar network and that alteration of expression or activity of vacuolar proton ATPase subunits is a general mechanism for TFP resistance in this yeast. PMID- 2192256 TI - BET1, BOS1, and SEC22 are members of a group of interacting yeast genes required for transport from the endoplasmic reticulum to the Golgi complex. AB - A subset of the genes required for transport from the endoplasmic reticulum (ER) to the Golgi complex in Saccharomyces cerevisiae was found to interact genetically. While screening a yeast genomic library for genes complementing the ER-accumulating mutant bet1 (A. Newman and S. Ferro-Novick, J. Cell Biol. 105: 1587-1594, 1987), we isolated BET1 and BOS1 (bet one suppressor). BOS1 suppresses bet1-1 in a gene dosage-dependent manner, providing greater suppression when it is introduced on a multicopy vector than when one additional copy is present. The BET1 and BOS1 genes are not functionally equivalent; overproduction of BOS1 does not alleviate the lethality associated with disruption of BET1. We also identified a pattern of genetic interactions among these genes and another gene implicated in transport from the ER to the Golgi complex: SEC22. Overproduction of either BET1 or BOS1 suppresses the growth and secretory defects of the sec22-3 mutant over a wide range of temperatures. Further evidence for genetic interaction was provided by the finding that a bet1 sec22 double mutant is inviable. Another mutant which is blocked in transport from the ER to the Golgi complex, sec21-1, demonstrates a more limited ability to be suppressed by the BET1 gene. The interactions we observed are specific for genes required for transport from the ER to the Golgi complex. The products of the genes involved are likely to have a direct role in transport, as bet1-1 and sec22-3 begin to display their mutant phenotypes within 5 min of a shift to the restrictive temperature. PMID- 2192257 TI - DNA-binding and transcriptional properties of human transcription factor TFIID after mild proteolysis. AB - The existence of separable functions within the human class II general transcription factor TFIID was probed for differential sensitivity to mild proteolytic treatment. Independent of whether TFIID was bound to DNA or free in solution, partial digestion with either one of a variety of nonspecific endoproteases generated a protease-resistant protein product that retained specific DNA recognition, as revealed by DNase I footprinting. However, in contrast to native TFIID, which interacts with the adenovirus major late (ML) promoter over a very broad DNA region, partially proteolyzed TFIID interacted with only a small region of the ML promoter immediately surrounding the TATA sequence. This novel footprint was very similar to that observed with the TATA factor purified from yeast cells. Partially proteolyzed human TFIID could form stable complexes that were resistant to challenge by exogenous templates. It could also nucleate the assembly of transcription complexes on the ML promoter with an efficiency comparable to that of native TFIID, yielding similar levels of transcription initiation. These results suggest a model in which the human TFIID protein is composed of at least two different regions or polypeptides: a protease resistant "core," which by itself is sufficient for promoter recognition and basal transcriptional levels, and a protease-sensitive "tail," which interacts with downstream promoter regions and may be involved in regulatory processes. PMID- 2192258 TI - Differential distribution of factors involved in pre-mRNA processing in the yeast cell nucleus. AB - The yeast cell nucleus has previously been shown to be divided into two regions by a variety of microscopic approaches. We used antibodies specific for the 2,2,7 trimethylguanosine cap structure of small nuclear ribonucleic acids (snRNAs) and for a protein component of small nuclear ribonucleoprotein particles to identify the distribution of small nuclear ribonucleoprotein particles within the yeast cell nucleus. These studies were performed with the fission yeast Schizosaccharomyces pombe and the budding yeast Saccharomyces cerevisiae. By using immunofluorescence microscopy and immunoelectron microscopy, most of the abundant snRNAs were localized to the portion of the nucleus which has heretofore been referred to as the nucleolus. This distribution of snRNAs is different from that found in mammalian cells and suggests that the nucleolar portion of the yeast nucleus contains functional domains in addition to those associated with RNA polymerase I activity. PMID- 2192259 TI - TEC1, a gene involved in the activation of Ty1 and Ty1-mediated gene expression in Saccharomyces cerevisiae: cloning and molecular analysis. AB - Ty and Ty-mediated gene expression observed in haploid cells of Saccharomyces cerevisiae depends on several determinants, some of which are required for the expression of haploid-specific genes. We report here the cloning and molecular analysis of TEC1. TEC1 encodes a 486-amino-acid protein that is a trans-acting factor required for full Ty1 expression and Ty1-mediated gene activation. However, mutation or deletion of the TEC1 gene had little effect on total Ty2 transcript levels. Our analysis provides clear evidence that TEC1 is not involved in mating or sporulation processes. Unlike most of the proteins involved in Ty and adjacent gene expression, the product of TEC1 has no known cellular function. Although there was no mating-type effect on TEC1 expression, our results indicate that the TEC1 and the a/alpha diploid controls on Ty1 expression are probably not cumulative. PMID- 2192260 TI - Mitosis-specific phosphorylation of nucleolin by p34cdc2 protein kinase. AB - Nucleolin is a ubiquitous multifunctional protein involved in preribosome assembly and associated with both nucleolar chromatin in interphase and nucleolar organizer regions on metaphasic chromosomes in mitosis. Extensive nucleolin phosphorylation by a casein kinase (CKII) occurs on serine in growing cells. Here we report that while CKII phosphorylation is achieved in interphase, threonine phosphorylation occurs during mitosis. We provide evidence that this type of in vivo phosphorylation involves a mammalian homolog of the cell cycle control Cdc2 kinase. In vitro M-phase H1 kinase from starfish oocytes phosphorylated threonines in a TPXK motif present nine times in the amino-terminal part of the protein. The same sites which matched the p34cdc2 consensus phosphorylation sequence were used in vivo during mitosis. We propose that successive Cdc2 and CKII phosphorylation could modulate nucleolin function in controlling cell cycle dependent nucleolar function and organization. Our results, along with previous studies, suggest that while serine phosphorylation is related to nucleolin function in the control of rDNA transcription, threonine phosphorylation is linked to mitotic reorganization of nucleolar chromatin. PMID- 2192261 TI - The extrachromosomal replication of Dictyostelium plasmid Ddp2 requires a cis acting element and a plasmid-encoded trans-acting factor. AB - Dictyostelium discoideum plasmid Ddp2 from the wild strain WS380B is a 5.8 kilobase (kb) supercoiled circle with a copy number of 300 per haploid genome. We previously described the construction of an extrachromosomally replicating transformation vector pnDeI carrying 4.7 kb of Ddp2 sequences (B. Leiting, and A. Noegel, Plasmid 20:241-248, 1988). In order to reduce the sequences required for extrachromosomal maintenance in D. discoideum, we characterized Ddp2 by sequence analysis, by deletion experiments, by transcription mapping, by electrophoretic mobility shift assays, and by expression of its single open reading frame in Escherichia coli. Two elements were involved in replication of Ddp2: a cis-acting sequence located on a 592-base-pair (bp) fragment that consisted of 220 bp of essential and 372 bp of auxiliary sequences, and a 2.7-kb open reading frame which most likely encodes a trans-acting factor. The cis- and trans-acting elements did not overlap and were shown to act independently from the location of the sequences encoding the trans-acting factor. PMID- 2192262 TI - Identification of the upstream activating sequence of MAL and the binding sites for the MAL63 activator of Saccharomyces cerevisiae. AB - Maltose fermentation in Saccharomyces species requires the presence of at least one of five unlinked MAL loci: MAL1, MAL2, MAL3, MAL4, and MAL6. Each of these loci consists of a complex of genes involved in maltose metabolism; the complex includes maltase, a maltose permease, and an activator of these genes. At the MAL6 locus, the activator is encoded by the MAL63 gene. While the MAL6 locus has been the subject of numerous studies, the binding sites of the MAL63 activator have not been determined. In this study, we used Escherichia coli extracts containing the MAL63 protein to define the binding sites of the MAL63 protein in the divergently transcribed MAL61-62 promotor. When a DNA fragment containing these sites was placed upstream of a CYC1-lacZ gene, maltose induced beta galactosidase. These sites therefore constitute an upstream activating sequence for the MAL genes. PMID- 2192263 TI - Interleukin-6 induction by tumor necrosis factor and interleukin-1 in human fibroblasts involves activation of a nuclear factor binding to a kappa B-like sequence. AB - Using variable-length deletion constructs of the 5'-flanking region of the human interleukin-6 (IL-6) gene linked to the chloramphenicol acetyltransferase gene, we showed that the region from positions -109 to -50 mediated the bulk of the response to tumor necrosis factor (TNF) or interleukin-1 (IL-1), while it was less responsive to forskolin. DNA mobility shift assays and DNase I footprinting analysis identified a nuclear protein from TNF- or IL-1-treated fibroblasts that bound to a region comprising a kappa B-like element located between positions -72 and -63 on the IL-6 gene. On the basis of these and other experiments, we conclude that TNF and IL-1 apparently activate IL-6 gene expression by closely related mechanisms involving activation of a NF-kappa B-like factor, whereas the pathway of IL-6 induction by forskolin is, in part, different. PMID- 2192264 TI - Involvement of cyclic AMP-dependent protein kinases in the signal transduction pathway for interleukin-1. AB - Expression of a highly specific protein inhibitor for cyclic AMP-dependent protein kinases in interleukin-1 (IL-1)-responsive cells blocked IL-1-induced gene transcription that was driven by the kappa immunoglobulin enhancer or the human immunodeficiency virus long terminal repeat. This inhibitor did not affect protein kinase C-mediated gene transcription, suggesting that cyclic AMP dependent protein kinases are involved in the signal transduction pathway for IL 1 in a number of responsive cell types. PMID- 2192265 TI - Induction of transformation and DNA synthesis after microinjection of raf proteins. AB - Full-length and N-terminal deletion mutants of human c-raf-1 cDNA were cloned into Escherichia coli expression plasmids. Bacterially expressed c-raf proteins were purified by anion-exchange, gel filtration, and affinity chromatography. Microinjection of mutant c-raf proteins into G0-arrested NIH 3T3 cells induced DNA synthesis and morphological transformation, whereas microinjection of full length c-raf had no effect. The amino terminus of the raf protein has an important negative regulatory influence; alteration of this region resulted in increased kinase activity and oncogenicity. PMID- 2192266 TI - Periodic biosynthesis of the human M-phase promoting factor catalytic subunit p34 during the cell cycle. AB - The product of the CDC2Hs gene is the protein kinase subunit of the M-phase promoting factor, which is required for entry into mitosis. The activity of this kinase is regulated in a cell cycle-dependent manner by reversible phosphorylation and through association with other proteins. We report here that in HeLa cells, the abundance of the CDC2Hs mRNA and the rate of synthesis of the encoded protein, p34, vary in a cell cycle-dependent manner. PMID- 2192267 TI - Transfected human beta-polymerase promoter contains a ras-responsive element. AB - beta-Polymerase is a vertebrate cellular DNA polymerase involved in gap-filling synthesis during some types of genomic DNA repair. We report that a cloned human beta-polymerase promoter in a transient expression assay is activated by p21v rasH expression in NIH 3T3 cells. A decanucleotide palindromic element, GTGACGTCAC, at positions -49 to -40 in the promoter is required for this ras mediated stimulation. PMID- 2192268 TI - [Viral myocarditis and classical virology. Clinico-virologic and experimental data]. AB - A viral etiology of myocarditis has been proven stringently only in a few cases and mostly enteroviruses have been shown to be involved. In fact, a virological diagnosis of viral myocarditis is still rarely possible today. Virus isolation from heart-tissue is hard to achieve and biopsies, if at all, are often performed too late. Successful virus isolation from other materials (e.g. faeces, throat swab) or a serological diagnosis of acute virus infection cannot easily be correlated etiologically with cardial symptoms, depending of course also on the kind of virus infection diagnosed. To prove an acute infection serologically a fourfold rise in antibody titer or for some viruses specific IgM has to be detected. A group specific diagnosis of "acute enterovirus infection" is not reliably possible at the moment. The neutralization test is the only relatively type specific test in enterovirus serology. Intraserotypic virus variants cannot be detected by normal serology. Even when determining neutralizing IgM antibodies, interpretation of results raises problems due to long persistence and possible cross reactivity. In case of suspected viral myocarditis clinicians should institute early and broad virological diagnostic measures. Virologists have to establish methods for virus or antigen determinations by molecular biological means. Furthermore, a fast and easy serological method for the diagnosis of an "acute enterovirus infection' would be very helpful. For research on the pathogenesis established animal models have to be used. PMID- 2192269 TI - [Lyme borreliosis: underdiagnosed?--overtreated?]. AB - Lyme borreliosis is a tick-borne mediated systemic inflammatory disorder caused by a newly recognized spirochete, Borrelia burgdorferi. Its clinical hallmark is an early expanding skin lesion, erythema chronicum migrans (ECM) which may be followed weeks to months later by neurological, cardiac, or joint abnormalities. Symptoms may be associated with any of these systems alone or in combination. All stages of Lyme borreliosis may respond to antibiotics, but treatment of early disease is the most successful. Foci of Lyme borreliosis are widely distributed within the USA and Europe and the disorder appears to be worldwide. Although there are some variations in clinical expression between the USA and Europe, the various syndromes, Erythema migrans (Afzelius), Meningopolyneuritis [Garin Bujadoux, Bannwarth (MPN)] are now generally subsumed under the name Lyme borreliosis. B. burdorferi is also responsible for an early skin lesion, Borrelia lymphozytom [Lymphadenosis cutis benigna (LCB)], and for a late one, Acrodermatitis chronica atrophicans (ACA), both seen primarily in Europe. In the USA joint abnormalities are the leading abnormalities in the later manifestation of the disease. Lyme borreliosis grew up in the last ten years as a new nosologic entity with some aspects for an infectious etiology of rheumatic disease. PMID- 2192270 TI - [Multicystic kidney dysplasia]. AB - The clinical course of 48 children (27 boys and 21 girls) with multicystic kidney dysplasia was analysed retrospectively. The patients were seen and treated at the Children's Hospital of Medical School Hannover between 1976 to 1989. There was no familial occurrence of the disease, yet in eight families various other renal diseases could be observed. In 20 patients the diagnosis of multicystic renal dysplasia was presumed by prenatal sonographic examination, in the other patients the diagnosis was established at the age between 1 day to 12 years. The first manifestations were palpable abdominal mass (n = 16), urinary tract infection (n = 4), casually because of a sonographic evaluation for other reasons (n = 4) and vomiting (n = 2). Associated malformations were found in 18 patients: cardiac malformations (n = 6), dysplasia of the other kidney (n = 5), ureter obstruction of the other kidney (n = 3), horseshoe kidney (n = 1) and others (n = 3). There was no hypertension and serum creatinine levels were normal in those children, who did not suffer from associated malformations of the other kidney. The multicystic kidney was removed operatively in 42 patients at the age of 3 days to 9.5 years (median 4 weeks). The prognosis of multicystic kidney dysplasia depends on associated renal and other malformations. PMID- 2192271 TI - [The effect of cyclosporin A on experimental glomerulonephritis in rabbits]. AB - The effect of cyclosporin A on the development of the autologous phase of experimental rabbit glomerulonephritis was assessed. The glomerulonephritis was induced by an intravenous injection of duck anti-rabbit glomerular basement membrane globulin into adult rabbits. After 5-7 days, diffuse proliferative glomerulonephritis with proteinuria and linear glomerular basement membrane deposits of rabbit IgG were observed in all animals. The cyclosporin A treatment was started simultaneously with the injection of duck globulin. This attenuated the glomerular lesion, resulting in a normal urinary excretion. The serum level of anti-duck globulin antibody was reduced. In the group of rabbits, receiving an injection of duck anti-rabbit glomerular basement membrane globulin, cyclosporin A treatment and an additional high dose of rabbit anti-duck globulin 8 days later, equally no glomerulonephritis was observed. However, no effect of cyclosporin A treatment on the duck immunoglobulin induced passive Arthus phenomenon was seen. PMID- 2192272 TI - [Nuclear magnetic resonance tomography in the differential diagnosis of adrenal gland hemorrhage and neuroblastoma in a newborn infant]. AB - Adrenal hemorrhages in newborns are usually diagnosed by sonography. Magnetic resonance imaging is indicated when morphological change, clinical appearance and follow-up do not allow differentiation of adrenal hemorrhage and neuroblastoma. Using artefact-suppressing sequences, the adrenal gland can be examined with modern MRI systems. The adrenal gland hemorrhage is characterized by a typical signal behaviour. If a haematoma persists over a longer period, a circular methemoglobin zone can be observed. An additional contrast application (Gadolinium-DTPA) can aid in demonstrating vascular tumors. PMID- 2192274 TI - Viruses can cause disease in the absence of morphologic evidence of cell injury: pathology in the absence of cell lysis--implication for pathologists' future study of disease. PMID- 2192273 TI - Biology of the central nervous system: special characteristics, common problems and common tools used today. PMID- 2192275 TI - AIDS and the central nervous system. PMID- 2192276 TI - It is difficult to see tomorrow from here. PMID- 2192277 TI - Morphologic correlates in gliomas: where do we stand? PMID- 2192278 TI - Cytogenetics and molecular genetics: their status and role in understanding the behavior of central nervous system neoplasms. PMID- 2192279 TI - Normal aging and Alzheimer's disease: growing problems. PMID- 2192280 TI - Amyloid and the central nervous system: the neurobiology, genetics and immunocytochemistry of a process important in neurodegenerative diseases and stroke. PMID- 2192281 TI - Prion diseases of the central nervous system. AB - Prions are novel, transmissible pathogens causing degenerative diseases in humans and animals. Kuru, CJD, and GSS illustrate the infectious, sporadic, and genetic mechanisms for human prion diseases, respectively. Scrapie of sheep and goats is the prototypic prion disorder since it was the first of these diseases to be transmitted to laboratory rodents. Over the past five years, a large amount of experimental data about the particles causing scrapie has been accumulated. Most of the information has been confirmed, and much of it is widely accepted. At times, this confirmed body of information has been overshadowed by what appears to be controversy due to the diverse terminology used by different laboratories. Prions are composed largely, if not entirely, of an abnormal isoform of the prion protein (PrP). The development of procedures to disperse infectious prions in detergent-lipid-protein complexes (DLPC) and liposomes has led to many advances. Previously, purified prions were aggregated into rod-shaped particles which are insoluble amyloids. Monoclonal antibodies (mAb) raised against PrP 27-30, which is derived from the scrapie PrP isoform (PrPSc) by limited proteolysis. have been used to purify scrapie prion infectivity in DLPC. Immunoaffinity purified fractions contain PrPSc and high prion titers. Polyclonal antibodies to PrP 27-30 were found to neutralize scrapie infectivity. These experimental results coupled with additional biochemical, genetic, pathologic, and cell biological lines of evidence have established that PrPSc is a major and necessary component of the scrapie prion. Both PrPSc and its cellular isoform (PrPc) are encoded by the same single-copy chromosomal gene. This is a major feature distinguishing prions from both viruses and viroids. To date, no prion-specific nucleic acid has been identified that is required for transmission of disease. PrPC and PrPSc are thought to have the same amino acid sequence but to differ due to some posttranslational process. Both PrPC and PrPSc are glycoproteins that possess Asn linked oligosaccharides and glycosyl phosphatidylinositol (GPI) anchors. Whether the features that distinguish PrPSc from PrPC arise from differences in their Asn linked oligosaccharides or GPI anchors is unknown. GSS and familial CJD are the only known human diseases that are both genetic and infectious. Recent studies have demonstrated that GSS is an autosomal dominant disorder and that a Pro--- Leu substitution at codon 102 of the PrP gene is linked to the development of GSS. Earlier investigations showed genetic linkage between an incubation time gene (Prn-i) and the PrP gene in inbred mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2192282 TI - Uracil-DNA glycosylase activity affects the mutagenicity of ethyl methanesulfonate: evidence for an alternative pathway of alkylation mutagenesis. AB - Mutagenesis induced by the alkylating agent ethyl methanesulfonate (EMS) is thought to occur primarily via mechanisms that involve direct mispairing at alkylated guanines, in particular, O6-ethyl guanine. Recent evidence indicates that alkylation of guanine at the O-6 position might enhance the deamination of cytosine residues in the complementary strand. To determine whether such deamination of cytosine could play a role in the production of mutations by EMS, the efficacy of this agent was tested in uracil-DNA glycosylase deficient (Ung) strains of Escherichia coli. The Ung- strains showed a linear response with increasing doses of EMS. This response was independent of the umuC gene product. In contrast, the Ung+ strains yielded a dose-squared response that became linear at higher doses of EMS when the cells were defective for the umuC gene product. These results support a model for mutagenesis involving the deamination of cytosines opposite O6-alkylated guanines followed by an error-prone repair event. PMID- 2192283 TI - Inhibitory action of peony root extract on the mutagenicity of benzo[a]pyrene. AB - The inhibitory effects of peony root extract on the mutagenicity of benzo[a]pyrene (B [a]p) have been investigated in the Salmonella typhimurium reversion test. Four kinds of experiments were performed: direct chemical reaction (1) between peony root extract and B [a]p, and (2) between peony root extract and active metabolite(s) of B [a]p, (3) inhibition of metabolic processes of B[a]p with S9 mix, and (4) inhibition of activation on mutagenicity. Peony root extract interfered with the action of enzymes in the S9 mix, and inactivated the activity of B[a]p metabolites. The bio-antimutagenic effect was assayed by reversion in Salmonella typhimurium TA98 and TA100. PMID- 2192284 TI - EMG evaluation of the floppy infant: differential diagnosis and technical aspects. AB - Electromyographic examination of the newborn and young infant provides a relatively uncommon challenge to most electromyographers. The usual reason for referral for electromyographic studies in the newborn and young infant is to evaluate a floppy baby. The electromyographer must not only be aware of important differences in normal physiologic parameters but must also be familiar with a spectrum of diseases that are not typically encountered in the adult. The results of electromyography must also be correlated with the normal maturation of neuromuscular function. Although the most common pathophysiologic mechanisms affecting the peripheral motor unit are infantile motor neuron disease and the congenital myopathies, a large number of other disease entities warrant careful consideration. PMID- 2192285 TI - Funding for nursing education: passthrough or pass over? PMID- 2192286 TI - Developing an effective business plan. AB - The cost-consciousness of today's health care industry demands that nurses function as business people as well as care givers. One critical business skill that nurses must develop is writing effective business plans. This article describes a framework for developing successful business plans for both beginning new services and expanding current nursing programs. PMID- 2192287 TI - Sample business plan. A laser section business plan. PMID- 2192288 TI - [L-tryptophan and the eosinophilic myalgia syndrome]. PMID- 2192290 TI - [Examination of the mediastinum in staging of primary bronchial carcinoma]. AB - Mediastinoscopy and CT are used to evaluate the mediastinum in patients with non small cell lung cancer to determine operability. Generally, the sensitivity and negative predictive value of CT are high, in a personal study in 150 patients 86% and 92%, respectively. When CT does not reveal enlarged lymph nodes, we recommend thoracotomy without mediastinoscopy. However, micrometastases in non-enlarged lymph nodes will be missed. All positive CT scans necessitate mediastinoscopy, because enlarged lymph nodes frequently are not invaded with tumour (in our study in 33%). CT used in this way will increase the percentage of positive results of mediastinoscopy. In patients with a peripheral tumour lymphogenic spread to the mediastinum is not uncommon (in our study in 22%) and mediastinal evaluation should not be omitted. In these patients mediastinoscopy is also of diagnostic value. PMID- 2192289 TI - [Elastase, elastase inhibitors and chronic obstructive lung diseases]. PMID- 2192291 TI - [Urinary tract infections in the elderly; what is its significance?]. PMID- 2192292 TI - Plasma exchange in systemic vasculitis. PMID- 2192293 TI - ANCA and systemic vasculitis. PMID- 2192294 TI - Anti-neutrophil cytoplasm antibodies in Wegener's granulomatosis: immunodiagnostic value, monoclonal antibodies and characterization of the target antigen. PMID- 2192295 TI - Amiodarone and thyroid function. PMID- 2192296 TI - Heterogeneity in Cushing's disease. AB - Some patients with Cushing's disease respond to neuropharmacological treatment, whereas others do not. This apparent heterogeneity has been attributed to the existence of a separate form of Cushing's disease of putative neurointermediate lobe origin as opposed to Cushing's disease of anterior pituitary origin. The present review summarizes recent observations in human and canine Cushing's disease which mitigate against this view. We propose that heterogeneity in Cushing's disease is related to heterogeneity of the normal anterior pituitary corticotroph. However, the most fundamental questions concerning the pathogenesis of Cushing's disease remain unanswered. PMID- 2192297 TI - Neutrophil involvement in inflammatory tissue damage. PMID- 2192298 TI - Vasculitis: a nephrologist's overview. PMID- 2192299 TI - Rationalizing the use of diagnostic neurotechnology: a binational perspective. PMID- 2192300 TI - Met-enkephalin immunoreactivity in the basal ganglia in Parkinson's disease and striatonigral degeneration. AB - This study concerns the expression of Met-enkephalin (MEnk) in the striatum and the external segment of the globus pallidus proper (GPe) in normal controls, idiopathic Parkinson's disease (PD), and striatonigral degeneration (SND). For this purpose, we developed a sensitive immunoperoxidase technique to visualize MEnk-positive patches in routinely prepared formalin-fixed paraffin-embedded striatal tissues. In comparison with normal controls, MEnk-positive patches and pallidal MEnk-positive axon terminals were strongly present in patients with PD, showing characteristic distribution patterns. By comparison, in SND patients, there was striking diminution of MEnk staining in the putamen and ventrolateral portion of the GPe, while MEnk patches were persistent in the caudate nucleus. PMID- 2192301 TI - DGAVP (Org 5667) in early Alzheimer's disease patients: an international double blind, placebo-controlled, multicenter trial. AB - We carried out a double-blind study of a vasopressin-related peptide, DGAVP citrate (Org 5667), in 115 patients with mild dementia, probable Alzheimer's type (DAT). Neither clinical rating scales nor psychometric tests revealed any improvement over 84 days with once-daily intranasal treatment with 2 different doses of DGAVP. We conclude that vasopressin-like peptides are not satisfactory therapeutic agents in DAT. PMID- 2192302 TI - Congenital inflammatory myopathy. AB - We present 3 patients with congenital inflammatory myopathy and summarize the literature. CNS involvement (microcephaly/intellectual delay) may or may not be present. Serum creatine kinase activity is elevated, the EMG is myopathic, and the muscle biopsy reveals inflammatory infiltrates, muscle fiber damage, and class I major histocompatibility complex products in muscle sarcolemma. Possible etiologies include intrauterine viral infection or an autoimmune process. Treatment with steroids may result in some motor improvement but has no effect on the CNS involvement. Despite a common time of presentation, these patients have a heterogeneous clinical profile, often suggesting a congenital muscular dystrophy syndrome. PMID- 2192303 TI - [A ceremony honoring Prof. Giuseppe Pezzuoli at the headquarters of the International College of Surgeons in Chicago]. PMID- 2192304 TI - [Venous Doppler velocimetry: ten years of development of a method]. AB - Doppler velocimetry enables three haemodynamic parameters that are extremely useful for the study of venous diseases to be evaluated: blood flow direction, the morphology of the velocity wave and venous pressure. These three parameters are used in association depending on the particular requirements of the diagnostic problem. In the case of suspected deep venous thrombosis, study of the morphology of the velocity wave and clinostatism pressure give good diagnostic possibilities for the iliaco-femoral axis but poor for the leg trunks. In post thrombotic syndrome, Doppler velocimetry is not so useful because the patient has to remain immobile during the examination while this specific pathology features insufficiency of the muscular pump during walking. In varicose disease, the investigation offers a very high diagnostic capability by evidencing the site and extent of valvular incontinence in the saphena and perforating vessels. The only limitation is the presence of numerous incontinent perforating vessels, but this is infrequent. In this pathology, Doppler v. has almost completely supplanted phlebography because it responds to the needs of modern medicine to replace invasive diagnostic investigations with non-invasive techniques that are equally effective. Finally, two other fields of application are very important for this investigation: the study of a patient with varices prior to saphenic stripping and prior to sclerotherapy. Definition of the origin and course of the reflux ways makes an optimal result possible, even allowing for the evolution of varicosity. PMID- 2192305 TI - [Experimental use of intraoperative pulse wave Doppler in the study of vascular microanastomosis]. AB - Personal experience with pulse wave Doppler (PWD) at 20 MHz with real time signal spectral analysis in FFT (Fast Fourier Transform), for the valuation of the vascular microanastomosis patency degree is reported. Fifty-nine Sprague-Dawley rats have been studied after abdominal aorta dissection: in 19 (group A) an organic stenosis has been simulated varying from 5% to 95% by a 8/0 silk suture; in 40 rats (group B and C) we the abdominal aorta was stitched with interrupted suture after transversal section. In the group C (20 rats) a longitudinal arteriotomy on abdominal aorta within 10-15 min from anastomosis was performed to value under microscopic control the suture line. The PWD technique is able to recognize stenoses more than 10% of intraluminal diameter, showing a higher sensibility than traditional techniques. PMID- 2192306 TI - [Spontaneous bilio-digestive fistula of lithiasic origin]. AB - Personal experience about 11 cases of spontaneous biliary enteric fistula caused by lithiasic disease operated in the General Surgical Clinic of the University of Siena from 1969 to 1988, is reported. The epidemiology, pathogenesis, symptomatology, indications for operation and various operating techniques performed are discussed. In the gallstone intestinal obstruction, the authors prefer to resolve immediately the obstruction, deferring to a later moment the specific operation for the treatment of the biliary enteric fistula and the lithiasic disease. PMID- 2192307 TI - [Endogastric migration of an Angelchik prosthesis. A case report and review of the literature]. AB - At first, the authors mention indications and way of placement of the Angelchik prosthesis. Then after a wide review of the literature, they describe the complications and results. Finally a case of penetration into the stomach of an Angelchik prosthesis is reported. It was favourably resolved by an operation. PMID- 2192308 TI - Encopresis: developmental, behavioral and physiological considerations for treatment. AB - Encopresis (soiling in the clothing) is a complex condition presenting a treatment challenge for health care providers. It is a disruptive event, placing both the child and family at risk for crisis. The definition, incidence, etiology and relevant medical, behavioral and developmental theory are discussed. A multi dimensional encopretic evaluation and management model is presented that addresses encopresis at developmental, behavioral and physiological levels. This system includes a detailed historical, demographic, behavioral and school performance profile of the child; appropriate physical and laboratory examinations; and a treatment approach that incorporates bowel evacuation, a high fiber diet, techniques of behavior modification, and maintenance on either contingent rectal cathartics or oral laxatives. If there are significant behavioral concerns and/or the family is dysfunctional, collaborative psychiatric management can be arranged. PMID- 2192309 TI - Hypoglycemia and endurance exercise: dietary considerations. AB - Until recently, common dietary prescription for chronic hypoglycemia has been a high-protein, low-carbohydrate regimen (Airola, 1977; Danowski, 1978). Increasing evidence suggests, however, that a diet rich in complex carbohydrates may be more suitable for those involved in endurance exercise (Costill & Miller, 1980; Sherman & Costill, 1984). Although little original research has been undertaken which deals with the effects of performance-enhancing nutritional techniques on the hypoglycemic exerciser, such practices need to be examined in order to understand the mechanisms involved. Specifically, carbohydrate loading would seem to be as important, if not more so, to the hypoglycemic individual as a means of supercompensating glycogen stores prior to endurance performance. The roles of pre-exercise supplements and carbohydrate feedings during exercise in this context are less clear. Although results are mixed, increasing evidence (Snyder et al., 1983; Okano et al., 1988) suggests that carbohydrates may be consumed before exercise with beneficial effects on performance. Because of rapid gastric emptying characteristic of reactive hypoglycemia, it would appear that pre exercise supplementation may be of particular value to the hypoglycemic exerciser. Further, recent studies (Bergstrom & Hultman, 1967; Coyle et al., 1983; Foster et al., 1986; Leatt & Jacobs, 1986; Horton, 1988) indicate that carbohydrate solutions taken during exercise are effective in maintaining serum glucose levels and improving endurance performance. Careful monitoring of nutritional factors would appear to be critical in creating a suitable dietary environment for the hypoglycemic endurance exerciser. PMID- 2192310 TI - The case for pulmonary angiography being the initial investigation in the management of patients suspected of having pulmonary embolism. PMID- 2192311 TI - Ventilation perfusion imaging for pulmonary embolism: match or mismatch? PMID- 2192312 TI - The importance of obtaining thyroid uptake measurement in patients with hyperthyroidism. PMID- 2192313 TI - Antenatal fetal assessment: an overview. AB - In the past two decades there have been dramatic changes in antenatal fetal assessment. As experience has been gained with new modalities, it has been possible to further decrease perinatal morbidity and mortality by modifying the indications and the frequency of testing, as well as the time of initiation. More antepartum assessment is performed today than ever before with the advent of new procedures. With the increasing complexity of multiple modalities and confounding risk factors it has become necessary to individualize the management of each high risk pregnancy. The clinician should attempt to identify which test or group of tests will insure the lowest perinatal mortality for a given risk factor. The specific test(s) utilized will depend on the population, the expertise of the personnel administering the test, and the manpower and equipment available. Antenatal fetal assessment is usually not performed unless one is prepared to modify obstetric management or expedite delivery when significant abnormalities are identified. The risks of delivery (maternal and neonatal) must then be weighed against the potential adverse effects of continuing the pregnancy. It should be recognized that there is no single "best test" for all clinical situations. It is important for the practicing physician to keep abreast of new developments in antenatal assessment and to be aware of recommended modifications in older applications. PMID- 2192315 TI - The contraction stress test. AB - The contraction stress test has long been used to assess fetal wellbeing in the antepartum period. The CST continues to be a valuable tool for practicing obstetricians when interpreted and managed according to previously published guidelines. More recent data have further defined the level of compromise at which the CST becomes abnormal. When compared to similar reports using the NST or biophysical profile, we are better able to define the capabilities of these various antepartum testing methods. Consequently, we were able to align antepartum testing schemes for the specific clinical situation as opposed to using one method for all patients. PMID- 2192314 TI - The nonstress test. AB - No currently available single test of fetal well-being is a universal, infallible clinical tool that stands apart from the more general context of the total pregnancy. It is tempting to place a substantial emphasis on the results of a test when medical decision-making is needed. Perhaps some sense of proportion should be invoked at this point, beginning with the recognition that fetal heart rate data, regardless of how they are obtained, provide a limited window to view the fetus and its environment. The fact remains that the relatively low incidence of real fetal compromise and subsequent poor outcomes biases the efficacy of the NST and other well-being tools. Most high-risk populations have a prevalence of poor outcomes of approximately 10 per cent; consequently, the target population for any assessment test is quite small. One must be reassured by the extremely large reported experience of Platt et al that nonstress testing is clinically useful in the overwhelming majority of cases. The NST appears to be an excellent predictor of the healthy fetus. The test is very good at predicting the fetus who does not require acute or premature obstetric intervention: it thereby prevents pregnancies from being subjected to unnecessary iatrogenic risks and from incurring tremendous medical and emotional costs. Can the NST be improved? I think that there is still considerable opportunity for making this test more effective and accurate. Our experience supports the concepts of standardized testing conditions, the use of baseline data in addition to reactivity alone, the prolongation of test sessions to achieve a more representative view of the fetus, and ultimately an automated analysis that will aid the clinician in making more reliable assessments of the fetal heart rate data present in the actual tracing. It would be useful to see the NST better integrated into management schemes that incorporate other assessment techniques as well as pertinent clinical data. The tendency to view the test as a "stand alone" modality has underscored weaknesses inherent in all surveillance methods that have a naturally limited perspective on complex developmental and adaptive problems. There is also a need for the development of academic standards so that collected experiences can be directly compared and communication of testing results made less ambiguous. These are some of the goals that should be set for the future and whose realization will effect better care for the unique population served by obstetricians. PMID- 2192316 TI - The fetal biophysical profile score: current status. AB - The cumulative experience with fetal biophysical profile scoring as a method for antepartum fetal risk assessment is now extensive. The cumulative data indicate that the method is sensitive for recognizing both the normal and compromised fetus. Moreover, the method appears to offer the advantage of grading various degrees of fetal compromise. The additional information gained by real-time ultrasound scanning (gestational age determination, fetal morphometrics, and fetal anomaly screening), while not an integral part of fetal biophysical profile scoring, nevertheless remains a critical aspect of antepartum fetal assessment. These data are collected simultaneously with the fetal biophysical profile score. It is impossible to separate cleanly the advantages of fetal biophysical profile scoring in isolation of this additional information collected. It would seem that such an attempt at separation is artificial since these data in combination provide more key information to the physician to guide fetal management. It seems reasonable to effect continued modification and improvement of the existing fetal biophysical profile score as a means of antepartum fetal risk assessment. PMID- 2192317 TI - Doppler velocimetry in obstetrics. AB - Doppler ultrasound velocimetry offers a noninvasive method for assessing velocities in the various components of the fetal circulation including the cardiac, umbilical, cerebral, and aortic flows. As the volumetric flow measurement in these circumstances is prone to significant errors, the major approach has been to analyze the maximum frequency shift envelope of the Doppler waveform. Numerous studies have demonstrated not only the feasibility, but also the diagnostic efficacy of this approach. The latter is particularly true in relation to the Doppler evaluation of the umbilical circulation in various complications of pregnancy. Although these findings do not establish the role of Doppler technology as a standard of practice, they clearly demonstrate its immense potential as a fetal surveillance technique. PMID- 2192318 TI - Ultrasound diagnosis of fetal anomalies. AB - Obstetric ultrasound permits the antenatal diagnosis of structural fetal anomalies. Every pregnant woman should have the option of a second trimester ultrasound examination in centers where examinations are available. PMID- 2192319 TI - Amniotic fluid assessment. AB - The mysterious environment surrounding the fetus for much of his or her life is now being explored with increasing fervor. Assessment of amniotic fluid in the early portion of pregnancy is now possible for fetal karyotype determination. This may permit early diagnosis of abnormal fetuses, increasing the options for patients. As pregnancy progresses, high-resolution ultrasound assessment of amniotic fluid volume is integral to the management of pregnancies at risk for oligohydramnios. Such pregnancies include those who are postdate and those with suspected intrauterine growth retardation. Additional evaluation and ultrasonography are recommended for evaluation of the fetus in this clinical situation. With either hydramnios or oligohydramnios, careful ultrasound assessment of the fetus is essential to rule out significant congenital malformations. Finally, the use of ultrasound-directed amniocentesis in later pregnancy permits an assessment of fetal lung maturity and of the fetus at risk for Rhesus immunization. Attention to detail should increase chances of a successful pregnancy outcome while decreasing neonatal morbidity and mortality. PMID- 2192321 TI - Evaluation of fetal and neonatal acid-base status. AB - Determination of fetal acid-base status, either at birth, intrapartum, or antepartum, is the gold standard for the diagnosis of fetal asphyxia. Indirect methods such as Apgar scores and fetal heart rate monitoring show at best only minimal correlation. It is evident that intrauterine hypoxia is a rare cause of central nervous system injury, and the finding of a normal acid-base status at birth should lead the clinician to search for other causes of central nervous system injury or birth depression. A combination of techniques including fetal acid-base assessment, electronic fetal heart rate monitoring, and thorough neonatal evaluation probably provides the best predictor of long-term outcome. Newer methods of umbilical cord sampling and acid-base determinations in the intrauterine growth retarded fetus hold some hope for the future. PMID- 2192320 TI - Invasive fetal assessment in the antepartum period. AB - Access to the fetus as a true patient is a recent development in maternal-fetal medicine. We review the major invasive techniques currently available for establishing diagnoses and providing treatments to the fetus. These include fetoscopy, fetal blood sampling, fetal transfusions, and fetal shunts. Indications, techniques, and complications are discussed. PMID- 2192322 TI - Fetal responses to external stimuli. AB - The fetus is clearly able to respond to various external stimuli. The nature of the response is related to gestational age, intact neurologic function, and also the behavioral state of the fetus. Of the various modalities described herein, vibroacoustic stimulation utilizing an artificial larynx appears to be clinically useful in both ante- and intrapartum management. The positive predictive value is excellent (greater than 99 per cent). The fetus who responds to the stimulus with an acceptable acceleration is uniformly nonacidotic. Like many other tests of fetal health, vibroacoustic stimulation is less useful in predicting fetuses in distress, as many fail to respond and yet show no signs of compromise. It is evident that there is no single test that is without false-positives; thus accurate assessment of fetal health will depend upon utilization of a variety of biophysical parameters. PMID- 2192323 TI - Obstetrical applications of computer technology. AB - Computer technology and the use of personal computers in obstetrics, particularly antepartum, and intrapartum fetal evaluation, are discussed. The future direction of computer technology in fetal assessment is also addressed. PMID- 2192324 TI - Fetal echocardiography. AB - Fetal echocardiography has become an essential tool for the thorough evaluation of the fetus at risk for congenital heart disease. This examination is now a part of standard medical practice and should no longer be considered investigational. Widespread use of fetal echocardiography is providing valuable insights into fetal cardiac embryology and physiology that have not been previously possible. PMID- 2192325 TI - Fetal body movement monitoring. AB - Recording fetal activity serves as an indirect measure of central nervous system integrity and function. The coordination of whole body movement, which requires complex neurologic control, is likely similar to that of the newborn infant. Short-term observations of the fetus are best performed using real-time ultrasound imaging. Monitoring fetal motion has been shown to be clinically worthwhile in predicting impending death or compromise, especially when placental insufficiency is longstanding. The presence of a vigorous fetus is reassuring. Perceived inactivity requires a reassessment of any underlying antepartum complication and a more precise evaluation by fetal heart rate testing or real time ultrasonography before delivery is contemplated. PMID- 2192326 TI - [The nature of a proliferation block in differentiated cells with heterokaryons as a model: various types of absence of proliferation in cells in terminal differentiation]. AB - Heterokaryons obtained by fusion of proliferating and terminally differentiated cells were studied. The data obtained suggest that mechanisms of proliferation arrest are different in macrophages on one hand and nucleate erythrocytes and polymorph leukocytes on the other. Macrophages appeared to be devoid of factors preventing replication in nontransformed and spontaneously immortalized cells. Inhibition of proliferation was probably due to certain modifications of macrophage genome which arise during differentiation and can be compensated by the effect of "immortalizing" oncogenes. On the contrary, nucleate erythrocytes and polymorphs evidently contain some factors mediating negative control of proliferation. For reactivation of DNA synthesis in these cell types after fusion with other cells the latter did not have to be immortalized. After cell fusion macrophages specifically inhibit DNA synthesis in cells containing active oncogenes. PMID- 2192327 TI - [Regulation of the spatial organization of the regenerating extremity in amphibians]. AB - Tests of the morphogenetic potency of the urodele limb regeneration blastema by a variety of transplantation experiments indicate that blastema is a self organizing system. The cells of blastema inherit a memory of their position on the three cardinal axes of the limb. This memory is called positional memory, and it is fundamental to recognizing loss of structure, triggering cellular interactions to replace missing structures, and specifying the level from which new structures can begin. Retinoic acid (RA) modifies the positional memory in all three cardinal axes of the limb. The vitamin proximalizes positional memory in the proximodistal axis, posteriorizes it in the anteroposterior axis, and ventralizes it in the dorsoventral axis. In vivo and in vitro assays of interactions between cell derived from different proximodistal limb levels, before and after treatment with RA, suggest that the cellular basis of positional memory resides in recognition/affinity property of the cell surface. RA probably modifies positional memory by modulating transcription, via a nuclear retinoid receptor. It is suggested that the genes involved in specifying positional memory, and whose transcription is therefore affected in regenerating limbs, are homeo box genes and genes that encode for molecules involved in determining the composition and architecture of the cell surface and extracellular matrix. PMID- 2192328 TI - [Detection of protease-sensitive factors with properties of beta-type transforming growth factor in early loach embryos]. AB - The blastoderm and yolk of Misgurnus fossilis L. late blastulae were subjected to acid-ethanol extraction and gel filtration on biogel P10 in 1 M CH3COOH. This resulted in isolation of polypeptides that induce substrate-independent proliferation of NIH-3T3 mouse fibroblasts in presence of epidermal growth factor. They did not compete for epidermal growth factor receptors of A-431 cells and inhibited substrate-independent proliferation of human lung carcinoma A-549 cells. These properties of the growth factor-like polypeptides from loach embryos are similar to those of transforming growth factor beta. PMID- 2192329 TI - Osteoplasty of the mandibular condyle with preservation of the articular soft tissue cover: comparison of fibrin sealant and sutures for fixation of the articular soft tissue cover in rabbits. AB - Fibrin sealant and sutures were compared for fixation of the articular soft tissue cover after it had been raised in association with osteoplasty of the mandibular condyle. Nine adult rabbits were operated on bilaterally with the use of fibrin sealant on one joint and sutures on the other joint. The rabbits were killed after 3 months. Macroscopic and histologic evaluations of the condyles did not reveal any appreciable differences between the two techniques. Fibrin sealant was, however, technically easier to apply than the sutures. It was concluded that fibrin sealant might be an alternative to sutures for fixation of the articular soft tissue cover after it has been raised in association with osteoplasty of the mandibular condyle. PMID- 2192330 TI - Characterization of the mycoflora from oral mucosal surfaces of some HIV-infected patients. AB - Oral mucosal surfaces from 54 patients seropositive for human immunodeficiency virus (HIV) were assayed for the presence of cultivable yeasts. Oral colonization with Candida albicans, represented by 6 biotypes, was evident in 35 persons. The closely related variant, Candida stellatoidea, was found in 3 patients. Single isolates of Candida parapsilosis, Candida glabrata, Candida tropicalis, and Candida paratropicalis were also identified. One patient harbored a population of Saccharomyces cerevisiae. The susceptibilities of these 43 isolates to clotrimazole and nystatin were compared by the disk diffusion technique. PMID- 2192331 TI - Desquamative gingivitis: preliminary observations with tetracycline treatment. AB - Fourteen patients admitted to our clinic were found to have desquamative gingivitis. They were treated with doxycycline monohydrate, a semisynthetic tetracycline, for 6 to 8 weeks. The gingival lesions were recorded photographically and were classified according to severity by means of a four graded mucosal index system. Biopsies for histologic and immunohistochemical examination were taken initially. Symptoms and clinical changes of the mucosa were recorded during the treatment period. Initial and final mucosal index scores were compared. A statistically significant improvement was obtained after tetracycline treatment. PMID- 2192332 TI - Foreign body gingivitis: an iatrogenic disease? AB - Gingival biopsy specimens from eight patients exhibiting a localized, erythematous, or mixed erythematous/leukoplakic gingivitis that was refractory to conventional periodontal therapy were examined histologically and by energy dispersive X-ray microanalysis. Histologic examination revealed variable numbers of small, usually subtle, sometimes equivocal, and occasionally obvious foci of granulomatous inflammation. Special stains for fungi and acid-fast bacilli were consistently negative. In all cases, the granulomatous foci contained particles of foreign material that were often inconspicuous and easily overlooked during routine histologic examination. Energy-dispersive X-ray microanalysis of these foreign particles disclosed Ca, Al, Si, Ti, and P in most lesions. However, other elements such as Zr, V, Ag, and Ni were found only in specific biopsy specimens. By comparing the elemental analyses, clinical features, and history of the lesions, strong evidence for an iatrogenic source of the foreign material was found in one case, and good evidence in five cases. In the remaining two patients, the source of the foreign particles remains unresolved. PMID- 2192333 TI - Experimental oral foreign body reactions. Commonly employed dental materials. AB - Foreign bodies and tissue reactions to foreign materials are commonly encountered in the oral cavity. The more common lesions include apical deposition of endodontic materials, mucosal amalgam and graphite tattoos, myospherulosis, oil granulomas, and traumatically introduced dental materials and instruments. Since many foreign materials are unidentifiable histologically, commonly used dental materials were experimentally implanted subcutaneously in rats to assess local host responses and characterize the nature of these materials microscopically. The histologic characteristics of these foreign body reactions are detailed herein. The implanted materials corresponded to reactions seen in human subjects. PMID- 2192334 TI - Pulpal and root sensitivity rated to periodontal therapy. AB - The purpose of this clinical investigation was to determine if periodontal treatment consisting of scaling, root planing, and periodontal surgery produced any change in pulpal or root sensitivity. Ten patients were tested, with a total of 84 observations. There were 42 periodontally treated teeth, with 42 contralateral teeth serving as control specimens. The teeth were evaluated with stimuli from an electric pulp tester, cold, and air. The electric pulp tester was found to be reliable in assessing the pulpal sensitivity. Neither the amount of periodontal destruction nor the extent of periodontal treatment had any effect on the pulp. Scaling and root planing had no significant effect on root sensitivity. Periodontal surgery was directly related to root sensitivity in terms of the extent of root surface exposure. An association was observed clinically between plaque accumulation after periodontal surgery and root sensitivity. PMID- 2192335 TI - [Regulation of vasopressin release in primary hypothyroidism and Addison's disease as well as in central diabetes insipidus]. AB - The osmoregulation of arginine-8-vasopressin (AVP) was investigated in 14 patients with primary hypothyroidism, in 6 with Addison's disease, and in 21 with central diabetes insipidus (CDI). In the latter disease the effect of histamine stimulus was also evaluated. Plasma AVP was measured by radioimmunoassay (RIA). Patients with primary hypothyroidism were classified into subgroups with elevated or normal basal levels of plasma AVP. A decreased osmotic threshold was found in hypothyroid patients with augmented basal AVP levels. Patients with Addison's disease exhibited an increased basal level of plasma AVP and a decreased osmotic threshold. CDI patients according to their AVP responses on osmotic stimulus fell into two groups: CDI I gave no response at all, while CDI II responded subnormally. CDI II exhibited blunted AVP release to histamine. The AVP reactions of the CDI I patients fell into two subgroups: CDI I/A had undetectable plasma AVP, whereas histamine evoked AVP release in CDI I/B. Patients with CDI II suffer from a partial CDI, while those with CDI I/A represent a complete form of the disease and CDI I/B presumably have an osmoreceptor failure. PMID- 2192337 TI - [The ancient history of cesarean section as reflected in literature and art]. PMID- 2192336 TI - [Effect of oral contraceptives on developmental anomalies and on the sex ratio of newborn infants]. AB - Several studies have suggested that maternal use of oral contraceptives before and early pregnancy may be associated with various congenital malformations. It had been found according to the computer-analysis of epidemiologic data of 17,031 single pregnancies--the use of oral contraceptives taken prior to conception or during early pregnancy has not been proved to increase the frequencies of the malformation of the offspring. On the other hand it was found, that oral contraception used before and in the early pregnancy increases the chance that infants delivered subsequently will be female. PMID- 2192339 TI - [The centenary of the birth of the author of Doctor Zhivago (Boris Leonidovich Pasternak)]. PMID- 2192340 TI - [The sweat test in cystic fibrosis]. AB - The high concentration of Na and Cl in the sweat of patients with Cystic Fibrosis is directly due to the primary pathogenetic defect, the reduced transport of Cl Ions through cell membranes of exocrine glands. The most reliable method for the sweat test is by Gibson and Cooke. In good correlation are the results of the Wescor Macroduct System. This method is easier to perform, but needs special instruments. PMID- 2192338 TI - [Transperitoneal nephrectomy of tumors at the beginning of the 20th century in Hungary]. PMID- 2192341 TI - [Cholestasis in young infants--practical procedures in differential diagnosis]. AB - Therapeutic advices and genetic or prognostic counselling depend on an early and accurate diagnosis of neonatal cholestasis. The outlined practical approach towards the differential diagnosis represents a stepwise decision making according to the urgency of underlying diseases. PMID- 2192342 TI - [Celiac disease (gluten sensitive enteropathy)]. AB - The frequency in the Austrian population of coeliac disease is approximately 1 in 1000 live births. The diagnosis is easy in most cases, if not obscured by an inconsiderate and inconsequent approach. The most frequent mistake is prescribing gluten free diet on trial before proving the diagnosis by small bowel biopsy. Failure to thrive, deficiency states and abnormal stools are the leading symptoms of coeliac disease. Careful inquiries and drawing of curves for length and weight usually give more information than expensive laboratory tests. Symptoms are frequently equivocal in relapses, in older children, and especially in adults. The basic prerequisite for the diagnosis of coeliac disease is the finding of subtotal villous atrophy in the small bowel mucosa. The only absolute contraindication against small bowel suction biopsy is a blood clotting defect. The small inconvenience from this procedure can be further reduced by experience and discipline of the examiner. Small bowel biopsies are performed in many paediatric hospitals. Thus, there is no excuse for omitting or delaying this procedure. Antigliadin antibodies and antiendomysial antibodies are of high diagnostic significance. The respective IgA antibodies show a high specificity, IgG antibodies a very high sensitivity. Thus, the decision for or against small bowel biopsy is made easier in doubtful cases, the evidence by villous atrophy for coeliac disease is approaching absolute proof. Gluten loading tests and multiple biopsies are therefore necessary only in rare cases. The very high frequency of certain HLA alleles in coeliac patients may also be used for diagnostic purposes. The pathogenesis of coeliac disease appears to involve genetic, immunologic, and environmental factors. The contribution of each of these factors may vary considerably in various patients. PMID- 2192343 TI - [Criteria for the assessment of data and measures in obesity in children]. AB - DEFINITION: Obese children have more than 20% overweight in relation to height. DIAGNOSTIC PROCEDURES: Estimation of serum concentrations of triglycerides, total , HDL- and LDL-cholesterol, and of blood pressure; oral glucose tolerance testing in patients with more than 40% overweight. INDICATION FOR THERAPY: More than 20% overweight in relation to height. EVALUATION OF THERAPEUTIC RESULTS: Main goal: less than 20% overweight; if not possible, stabilisation of overweight between 20 and 30%; if not possible in cases of severe obesity (more than 60% overweight): Either reduction of overweight more than 40% (in patients with 80% overweight or more) or reduction of overweight more than 20 and less than 40% (in patients with 60-70% overweight) and stabilisation of overweight within these ranges respectively. Therapeutic results should be reported in relation to the end of therapy as short term results: at most 2 years, as medium term results: at least 3 years, and as long term results: after growth stop. PMID- 2192344 TI - [Hereditary fructose intolerance]. AB - The paper gives an overview of current diagnostic procedures in patients with clinical suspicion of hereditary fructose intolerance. On the basis of the literature and of a 9 years' experience at the Department of Paediatrics of the University of Graz a different approach according to the clinical condition of the patients is proposed (good clinical condition, severe liver disease, or bad clinical condition--i.e. liver biopsy is ethically not justified). The aim of this approach is to minimize invasive procedures for the children. PMID- 2192346 TI - American Pediatric Society, centennial celebration program. Washington,D.C., May 3, 1988. PMID- 2192345 TI - Advent of the second century of pediatrics. PMID- 2192347 TI - Treating genetic diseases: lessons from three children. PMID- 2192348 TI - Questions to the past that resonate in the present. PMID- 2192349 TI - Developmental biology: preventive medicine for neonatology. PMID- 2192350 TI - Brain injury in the premature infant: is it preventable? PMID- 2192351 TI - Neonatal pediatrics at the century mark. PMID- 2192352 TI - Centennial history of the APS. PMID- 2192353 TI - Infectious diseases and the last 100 years in the American Pediatric Society. PMID- 2192354 TI - Contribution of American pediatricians to treatment of diarrheal dehydration. PMID- 2192355 TI - The role of the contralateral limb in below-knee amputee gait. AB - Very little quantitative biomechanical research has been carried out evaluating issues relevant to prosthetic management. The literature available suggests that amputees may demonstrate an asymmetrical gait pattern. Furthermore, studies suggest that the forces occurring during amputee gait may be unequally distributed between the contralateral and prosthetic lower limbs. This study investigates the role of the contralateral limb in amputee gait by determining lower limb joint reaction forces and symmetry of motion in an amputee and non amputee population. Seven adult below-knee amputees and four non-amputees participated in the study. Testing involved collection of kinematic coordinate data employing a WATSMART video system and ground reaction force data using a Kistler force plate. The degree of lower limb symmetry was determined using bilateral angle-angle diagrams and a chain encoding technique. Ankle, knee and hip joint reaction forces were estimated in order to evaluate the forces acting across the joints of the amputee's contralateral limb. The amputees demonstrated a lesser degree of lower limb symmetry than the non-amputees. This asymmetrical movement was attributed to the inherent variability of the actions of the prosthetic lower limb. The forces acting across the joints of the contralateral limb were not significantly higher than that of the non-amputee. This suggests that, providing the adult amputee has a good prosthetic fit, there will not be increased forces across the joints of the contralateral limb and consequently no predisposition for the long-term wearer to develop premature degenerative arthritis. PMID- 2192356 TI - Biomechanics and shape of the above-knee socket considered in light of the ischial containment concept. AB - In recent years considerable interest has been generated in the United States and abroad about new style above-knee prosthetic sockets, variously referred to as Narrow M-L, NASNA, CAT-CAM and SCAT-CAM. More than a little confusion has attended the process. Moreover, the impression has been created that they are not governed by the basic biomechanical rules identified by Radcliffe as affecting the quadrilateral socket. Attention has come to be focused on the role of ischial containment and the term Ischial Containment (IC) socket is enjoying widespread use. This paper reviews many of the critical features of such sockets with the goal of first demonstrating that many of these features are dictated by the requirements of ischial containment, and second that the principles set forth by Radcliffe are fully applicable. The paper concludes with a brief discussion of the alignment principles associated with Long's Line. PMID- 2192357 TI - Target Detection Assay (TDA): a versatile procedure to determine DNA binding sites as demonstrated on SP1 protein. AB - We developed a rapid method designated Target Detection Assay (TDA) to determine DNA binding sites for putative DNA binding proteins. A purified, functionally active DNA binding protein and a pool of random double-stranded oligonucleotides harbouring PCR primer sites at each end are included the TDA cycle which consists of four separate steps: a DNA protein incubation step, a protein DNA complex separation step, a DNA elution step and a polymerase chain reaction (PCR) DNA amplification step. The stringency of selection can be increased in consecutive TDA cycles. Since tiny amounts of retained DNA can be rescued by PCR, buffer systems, salt concentrations and competitor DNA contents can be varied in order to determine high affinity binding sites for the protein of choice. To test the efficiency of the TDA procedure potential DNA binding sites were selected by the DNA binding protein SP1 from a pool of oligonucleotides with random nucleotides at 12 positions. Target sites selected by recombinant SP1 closely matched the SP1 consensus site. If DNA recognition sites have to be determined for known, mutated or putative DNA binding proteins, the Target Detection Assay (TDA) is a versatile and rapid technique for consideration. PMID- 2192358 TI - Characterisation of sequences required for RNA initiation from the PGK promoter of Saccharomyces cerevisiae. AB - In the phosphoglycerate kinase (PGK) gene of yeast, as in other highly expressed yeast genes, the sequences surrounding the site of RNA initiation have a loosely conserved structure of a CT rich stretch followed by the tetranucleotide CAAG. Using internal deletions and insertions we have identified the elements in the PGK promoter which are required for correct RNA initiation at the CAAG sequence at -39. The results indicate that two different components of the PGK promoter contribute to correct RNA initiation, the TATA homologies, located at -152 and 113, and the sequences at the site of initiation. Both TATA elements can function in RNA initiation. Deletion of the upstream TATA element, TATAI, results in slightly heterogeneous RNA initiation, but the majority of the RNA initiates correctly. Deletion of both the PGK TATA elements results in the majority of the RNA initiating at sites downstream from the wild-type I site, within the structural gene between +40 to +80. The CT rich box is not essential for correct mRNA initiation as shown by deletion analysis. The site of RNA initiation in the PGK promoter appears to be determined by sequences located immediately 5' of the CAAG sequence motif. This short sequence, ACAGATC, when located the correct distance from the TATA elements may be sufficient to determine a discrete initiation site. PMID- 2192359 TI - Regulated expression of the Saccharomyces cerevisiae DNA repair gene RAD7 in response to DNA damage and during sporulation. AB - The RAD7 gene of Saccharomyces cerevisiae affects the proficiency of excision repair of DNA damaged by UV light. Here, we report our studies on the regulation of the RAD7 gene in response to UV irradiation and during sporulation. RAD7 transcript levels increased 6-fold within 40 min of exposure of cells to 37 J/m2 of UV light. Higher UV doses also elicited rapid increases in the level of RAD7 mRNA. RAD7 mRNA levels increased in sporulating MATa/MAT alpha diploid cells, but not in the asporogenous MATa/MATa strain exposed to sporulation conditions. The increase in RAD7 mRNA level in MATa/MAT alpha cells was 15-fold after 6 h and 9 fold after 7 h in sporulation medium; thereafter, RAD7 mRNA levels declined. Periodic transcription of RAD7 during sporulation suggests a role for RAD7 in this process. PMID- 2192360 TI - Methylase-limited partial NotI cleavage for physical mapping of genomic DNA. AB - Partial cleavage of DNA with the restriction endonuclease NotI (5'...GC/GGCCGC...3') is an important technique for genomic mapping. However, partial genomic cleavage with this enzyme is impaired by the agarose matrix in which the DNA must be suspended. To solve this problem we have purified the blocking methylase M. BspRI (5'...GGmCC...3') for competition digests with NotI. The resulting methylase-limited partial DNA cleavage is shown to be superior to standard techniques on bacterial genomic DNA. ABBREVIATIONS: bp, base-pair; kb, one thousand base-pairs; Mb, one million base-pairs; Tris, Tris(hydroxy methyl)aminomethane; EDTA, (ethylenedinitrilo)tetraacetic; beta-ME, beta mercaptoethanol; PMSF, phenyl methyl-sulfonyl fluoride; PEG, polyethyleneglycol (MW = 8000); 3H, tritium; SAM, S-adenosylmethionine; KGB, potassium glutamate buffer; DTT, dithiothreitol; IPTG, isopropyl-beta-D-thiogalactopyranoside; BSA, bovine serum albumin. PMID- 2192361 TI - Supercoil-induced unusual DNA structures as transcriptional block. AB - The transcriptional activity of pBR322 form V DNA template, a topologically unlinked, highly supercoiled molecule having unusual structures around or within coding regions was studied. Significant transcription was observed in vitro from this template despite high levels of supercoiling. An attenuated transcript, initiated accurately from the P4 promoter of rep gene, was observed which indicated pausing of E. coli RNA polymerase within the gene. This pausing could be removed by relieving the torsional stress implying that a supercoil induced structural alteration within the gene was acting as a transcriptional block. A stabilized unusual structure, most likely a cruciform, was found to be responsible for the elongation block. Absence of initiation from the tetR gene was correlated with the unusual structure present within its promoter region in form V DNA. These in vitro studies show that structural alterations within natural DNA could act as transcriptional blocks both at the level of initiation and elongation. PMID- 2192362 TI - A sequence pattern that occurs at the transcription initiation region of yeast RNA polymerase II promoters. AB - Saccharomyces cerevisiae mRNA 5'-ends map at a variable distance from the TATA element. The mechanism for the choice of the transcription Initiation Region (IR) over other neighbouring sequences is not clearly understood. Sequences on the coding strand flanking the IR of 95 yeast RNA polymerase II promoters have been compared. They indicate the following pattern: statistically, a preponderance of T residues beginning as far as 30 nucleotides upstream and ending approximately 10 nucleotides upstream of the IR, and a preponderance of A residues from approximately 8 nucleotides upstream of the transcription initiation-site onward. The switch in base composition noted above thus occurs over a short region that is centered typically -9 nucleotides with respect to the major transcription start-site. We call this overall sequence pattern the locator. It is more evident among strong promoters than weak ones, suggesting a role in transcription initiation. The promoter of the TCM1 gene (coding for ribosomal protein L3) has a typical locator in the region of its IR. In an attempt to confirm the role of this sequence motif in defining the IR, deletions were introduced between the TATA element and the IR of the TCM1 gene. In most deletions, the new transcription start-sites are found within a recognizable locator, supporting the suggestion that this sequence pattern is important in defining the IR. These data appear to indicate that in yeast the IR is defined by a pattern of base composition situated at a suitable distance from the TATA element. PMID- 2192363 TI - Nucleotide cDNA and complete deduced amino acid sequence of a Trypanosoma cruzi ribosomal P protein (P-JL5). PMID- 2192364 TI - Sequence and molecular structure of the Aspergillus nidulans yA (laccase I) gene. PMID- 2192365 TI - [Investigation of total body irradiation in patients with advanced centrocytic centroblastic and centroblastic lymphomas. I. Therapeutic technics]. AB - The own technique of 60CO total body irradiation of patients with advanced non Hodgkin's lymphomas is presented. The dose in the center of the pelvis has been theoretically calculated and verified by measurements on the anatomical phantom of the Alderson-Rando type and by in vivo measurements on patients applying the intrarectal probe with thermoluminescence dosimeters. PMID- 2192366 TI - [Investigation of total body irradiation in patients with advanced centrocytic centroblastic and centroblastic lymphomas. II. Clinical observations]. AB - A pilot group of 19 patients with advanced non-Hodgkin's lymphomas has been treated applying the own technique of total body irradiation. The total dose amounted to 200 cGy, delivered in 20 fractions with triple weekly fractionation. The additional irradiation of neoplastic foci persisting after total body irradiation has been also applied. Good tolerance, low toxicity and high efficacy of the total body irradiation of patients with advanced centrocytic-centroblastic lymphomas previously chemically untreated appeared evident. PMID- 2192367 TI - Ethical issues in human genetic technology. AB - The United States and several nations in the developed world have initiated efforts to map and sequence the human genome. The knowledge derived from these efforts will have a profound influence on the practice of medicine. This article reviews the technical developments in the field of human genetics and reviews the ethical issues relevant to the pediatrician in the application of this technology in prenatal screening, presymptomatic screening, carrier screening, and gene therapy. The complexity of these issues warrants caution in the clinical application of these tools and will require a better understanding of human genetics by health professionals and the public. PMID- 2192368 TI - [Noninvasive methods for early diagnosis of chronic cor pulmonale in chronic obstructive respiratory tract diseases]. PMID- 2192369 TI - [Oral therapy with beta-2-sympathomimetic drugs: comparative study of the bronchospasmolytic effect of tulobuterol and fenoterol in patients with reversible airway obstruction]. AB - In a multicentre, single-blind study, the bronchospasmolytic effect of a single oral dose of tulobuterol 2.0 mg and of fenoterol 2.5 mg was compared in 26 patients suffering from reversible airways obstruction. The bronchospasmolysis achieved with the oral application of tulobuterol and fenoterol is qualitatively satisfactory and reliable, the effect of tulobuterol persisting for a longer period than that of fenoterol. PMID- 2192370 TI - Impaired insulin secretion in the neonatal rhesus monkey after chronic hyperinsulinemia in utero. AB - The secretion of insulin by the pancreas of the newborn rhesus monkey that had been made experimentally hyperinsulinemic in utero was studied in 18 animals. Chronic in utero hyperinsulinemia was produced by the continuous subcutaneous delivery of 4.75 units of insulin per day for 18 +/- 1 days. After delivery, the insulin-containing pump was removed to allow neonatal insulin levels to drop to normal levels. By 6.5 +/- 1.0 hr after pump removal, plasma glucose, insulin, and C-peptide immunoreactivity (CPIR) were comparable in the control and experimental animals. At that point 300 micrograms of glucagon/kg body weight was given iv to stimulate insulin secretion. After 30 min a significant elevation (expressed as the percentage of basal levels) in plasma glucose by 250%, insulin by 200%, and CPIR by 200% was observed in the control animals. In contrast, no changes in plasma insulin or CPIR concentrations occurred, with an attenuated glucose response that was only one-fifth of the control response, in the experimental animals. These results along with the observed lowered concentrations of CPIR in the plasma and insulin in the pancreas at birth can be interpreted as evidence that insulin is an inhibitor of its synthesis and secretion in utero and that this abnormal intrauterine environment causes changes that persist into extrauterine life. PMID- 2192371 TI - Differential effects of growth factors on [3H]thymidine incorporation and [125I]iodine uptake in FRTL-5 rat thyroid cells. AB - We studied the effect of several growth factors on DNA synthesis and function of FRTL-5 rat thyroid cells by simultaneous measurement of [3H]thymidine incorporation and [125I]iodide uptake. Endothelial cell growth factor, fibroblast growth factor, platelet-derived growth factor, and insulin-like growth factor I stimulated thymidine incorporation in a dose-dependent manner without the parallel increase of [125I]iodide uptake. These growth factors had an additive effect with thyroid-stimulating hormone (TSH) on thymidine incorporation, but they inhibited TSH-stimulated iodide uptake. Bombesin stimulated thymidine incorporation and inhibited TSH-stimulated iodide uptake; epidermal growth factor and gastrin-releasing peptide 10 had neither effect. None of the growth factors studied affected iodide uptake in the absence of TSH. Of the growth factors tested, endothelial cell growth factor, fibroblast growth factor, insulin-like growth factor bombesin, and platelet-derived growth factor all share similar differential effects on FRTL-5 cells: stimulation of DNA synthesis, potentiation of the effects of TSH on DNA synthesis, and attenuation of the effects of TSH on cell function. The data suggest that these growth factors may play important roles in regulation of thyroid function. PMID- 2192372 TI - Gonadotropin-releasing hormone-associated peptide immunoreactivity in bovine colostrum. AB - Gonadotropin-releasing hormone(GnRH)-associated peptide (GAP) is a 56-amino acid peptide found on the C-terminal of the GnRH (also called luteinizing hormone releasing hormone) precursor and is assumed to be co-produced with GnRH. The purpose of this report is to demonstrate the presence of GAP immunoreactivity in bovine colostrum. Radioimmunoassay of acidified methanolic extracts demonstrated a concentration of GAP immunoreactivity of approximately 1.5 +/- 0.1 pmol/g dry skim bovine colostrum. Gel filtration (Sephadex G-10) and high-performance liquid chromatography of extracts containing GAP immunoreactivity showed it to be of low molecular weight and a high hydrophobic character. The presence of GAP immunoreactivity in bovine colostrum suggests that the GnRH precursor is synthesized and processed in mammary tissue itself. PMID- 2192373 TI - Balance performance on the postural stress test: comparison of young adults, healthy elderly, and fallers. AB - The purpose of this study was to compare the postural responses of three groups of individuals--healthy young adults (n = 42; age, 20-40 years); healthy, community-dwelling, elderly individuals (n = 66; age, 60-102 years), and elderly individuals with a history of frequent falls (n = 10; age, 66-95 years)--using the postural stress test (PST). The PST is a simple, clinically applicable, quantitative measure of an individual's ability to withstand a series of graded destabilizing forces applied at the level of the subject's waist. Elderly fallers tend to score lower on the PST than elderly nonfallers, but age-related differences in postural responses during the PST have not been established. Each subject underwent the PST using a method and scoring procedure described previously. Results of this study confirm previous findings that elderly fallers score significantly lower on the PST than either young adult or nonfalling elderly individuals. This study also showed that there was no difference in balance strategy scores between the young adults and the healthy elderly subjects. Therefore, it appears that poor performance on the PST cannot be attributed to age alone, but may be predictive of pathological processes that predispose an individual to frequent falls. PMID- 2192374 TI - Effect of a tone-inhibiting dynamic ankle-foot orthosis on stride characteristics of an adult with hemiparesis. AB - A single-subject, alternating-treatment design was used to investigate differences in stride characteristics of a hemiparetic subject under three conditions: 1) barefoot, 2) using a prefabricated plastic molded ankle-foot orthosis (AFQ), and 3) using a tone-inhibiting dynamic ankle-foot orthosis (TIAFO). Five barefoot baseline sessions were conducted. Following these baseline sessions, the three conditions were randomly varied during each of 12 alternating treatment sessions. Data analysis revealed a significant improvement in walking velocity, step length, and stance time on the hemiparetic limb and a significant decrease in cadence when either the AFO or the TIAFO condition was compared with the barefoot condition. The TIAFO was associated with a significant increase in walking velocity and step length when evaluated against the prefabricated AFO. The subject reported that use of the TIAFO increased his ability to ambulate distances and that the TIAFO was more comfortable and less restrictive than the prefabricated AFO. The results suggest that the TIAFO may be a promising alternative to conventional orthotic management of adults with hemiparesis. PMID- 2192375 TI - Canadian therapists' priorities for clinical research: a Delphi study. AB - Clinically relevant physical therapy research questions were developed by a Delphi technique among 55 teaching hospital physical therapists. The Delphi technique used in this study involved three rounds of questionnaires that included characteristics of anonymity, feedback, ranking with statistical scoring, and use of informed respondents. Fifty-eight initial research questions were narrowed to 11 according to their potential benefit for the patient, for the practice of physical therapy, and for decreasing health care costs. A literature review revealed that each of the 11 questions were as yet unanswered. The use of the survey results to guide and plan for clinical research in physical therapy is discussed. PMID- 2192376 TI - Interpreting results of diagnostic tests. PMID- 2192377 TI - Repair of UV-damaged incoming plasmid DNA in Saccharomyces cerevisiae. AB - A whole-cell transformation assay was used for the repair of UV-damaged plasmid DNA in highly transformable haploid strains of Saccharomyces cerevisiae having different repair capabilities. Six rad alleles were selected from the three epistasis groups: rad 1-1 and rad2-1 from the RAD3 group, rad6-1 and rad18-2 from the RAD6 group, and rad52-1 and rad54-1 from the RAD52 group. Cells carrying single, double and triple rad alleles were transformed to uracil prototrophy by centromeric plasmid DNA (YCp19) modified in vitro with UV (254 nm). Surviving fractions were calculated as the number of transformants at each fluence relative to the number of transformants with unirradiated plasmid DNA. The sensitivity of incoming DNA in single rad mutants shows that most repair is carried out by excision repair and a RAD18-dependent process. In the rad52-1 host, the sensitivity of incoming DNA was intermediate between those found in RAD+ and rad2 1 hosts, suggesting the involvement of a recombinational repair process. Non epistatic interactions were observed between rad alleles belonging to different epistasis groups. This provides validation for the classification of the three epistasis groups concerning the repair of chromosomal DNA for UV-incoming DNA. In both rad1-1 rad6-1 and rad1-1 rad18-2 rad54-1 hosts, the mean fluence for one lethal event corresponds approximately to one pyrimidine dimer per plasmid molecule, indicating that they are absolute repairless hosts for incoming DNA. A comparison between cell and plasmid survival reveals that there are differences in the repairability of both chromosomal and incoming DNA. The large effect of rad6-1 mutation on cell survival and the small effect on incoming DNA suggest that, in the RAD+ strain, the RAD6 product may be essential for the repair processes which act on chromosomal DNA, but not for those which act on incoming DNA. It is proposed that in yeasts postreplication repair of incoming DNA is limited to supercoiled molecules with 1-2 pyrimidine dimers that can initiate replication. PMID- 2192378 TI - Studies on insulin-like substances in Korean red ginseng. AB - Korean red ginseng powder was found to contain adenosine and an acidic substance which inhibited epinephrine-induced lipolysis and stimulated insulin-mediated lipogenesis from glucose (3, 4). In the present experiment, the chemical structure of this acidic substance is determined to be pyro-glutamic acid. Pyroglutamic acid exhibits selective modulations toward the opposite metabolic pathways in rat adipocytes; it inhibits the lipolysis but rather stimulates the lipogenesis. Based on these results, we suggest to call these substances (adenosine and pyro-glutamic acid) "selective modulators". PMID- 2192379 TI - Randomized, double-blind study of freeze-dried Urtica dioica in the treatment of allergic rhinitis. AB - Ninety-eight individuals took part in a double-blind randomized study comparing the effects of a freeze-dried preparation of Urtica dioica (stinging nettles) with placebo on allergic rhinitis. Sixty-nine individuals completed the study. Assessment was based on daily symptom diaries, and global response recorded at the follow-up visit after one week of therapy. Urtica dioica was rated higher than placebo in the global assessments. Comparing the diary data Urtica dioica was rated only slightly higher. PMID- 2192380 TI - In vitro antimalarial activity of Coutarea latiflora and Exostema caribaeum extracts on Plasmodium falciparum. AB - The medicinal plants, Coutarea latiflora Sesse & Moc. ex. DC. (Hintonia latiflora Bullock) (Rubiaceae) and Exostema caribaeum (Jacq.) Roem. et Schult. (Rubiaceae) were examined for antimalarial properties. Among different crude solvent extracts of the stem bark, the hydrolysed ethyl acetate extracts were shown to have the most potent in vitro antimalarial activity. One compound isolated from the ether extract from Exostema caribaeum showed only moderate activity. PMID- 2192381 TI - Psychodynamic treatment of schizophrenia: is there a future? PMID- 2192382 TI - Madness at the crossroads: John Home's letters from the Royal Edinburgh Asylum, 1886-87. AB - A detailed and critical discussion of John Home, a certified inmate of the Royal Edinburgh Asylum during 1886-87, is presented from a historical perspective which is sensitive to the respective positions of the practitioner and the patient. Particular attention is paid to the letters Home wrote during his confinement and their significance for understanding asylum life during this period. Some interpretative difficulties surrounding the use of medical records, patient letters and other related evidence are also examined. PMID- 2192384 TI - Automatism, medicine and the law. AB - The law on automatism is undergoing change. For some time there has been a conflict between the medical and the legal views. The medical profession believes that the present division between sane and insane automatism makes little medical sense. Insane automatism is due to an internal factor, that is, a disease of the brain, while sane automatism is due to an external factor, such as a blow on the head or an injection of a drug. This leads to the situation where, for example, the hypoglycaemia resulting from injected insulin would be sane automatism, while hypoglycaemia while results from an islet tumour would be insane automatism. This would not matter if the consequences were the same. However, sane automatism leads to an acquittal, whereas insane automatism leads to committal to a secure mental hospital. This article traces the development of the concept of automatism in the 1950s to the present time, and looks at the anomalies in the law as it now stands. It considers the medical conditions of, and the law relating to, epilepsy, alcohol and drug automatism, hypoglycaemic automatisms, transient global amnesia, and hysterical automatisms. Sleep automatisms, and offences committed during a somnambulistic automatism, are also discussed in detail. The article also examines the need of the Courts to be provided with expert evidence and the role that the qualified medical practitioner should take. It clarifies the various points which medical practitioners should consider when assessing whether a defence of automatism is justified on medical grounds, and in seeking to establish such a defence. The present law is unsatisfactory, as it does not allow any discretion in sentencing on the part of the judge once a verdict of not guilty by virtue of insane automatism has been passed. The judge must sentence the defendant to detention in a secure mental hospital. This would certainly be satisfactory where violent crimes have been committed. However, it is inappropriate in many cases where non-violent confusional crimes, such as petty larceny, have been committed. Suggestions are made for desirable changes in the law. PMID- 2192383 TI - The Nottingham Study of Neurotic Disorder: relationship between personality status and symptoms. AB - Two hundred and ten psychiatric patients with one of three DSM-III diagnoses, generalized anxiety disorder (N = 71), panic disorder (N = 74) or dysthymic disorder (N = 65), were included in a clinical trial in which diazepam, dothiepin or placebo tablets, cognitive and behaviour therapy, or a self-help package were given over ten weeks. Personality status was assessed independently using a structured interview, the Personality Assessment Schedule. One hundred and ninety eight patients had personality assessments, 89% with a close informant. Thirty six per cent had a personality disorder and these patients had more severe psychopathology than those with no personality disorder. Personality disorder was more common in patients with dysthymic disorder and this group responded less well to treatment. The category of personality disorder had no apparent influence on symptoms. PMID- 2192385 TI - [Overview of brief psychotherapies--a basis for discussion of problem-oriented therapy]. AB - Historical and pragmatic reasons justify short term practice of psychotherapy. Some of the better known methods are discussed in respect to their concept, indication and setting: Malan and the Tavistock-group; Mann: Time limited psychotherapy; Sifneos: STAP, Short term anxiety provoking psychotherapy; Davenloo: Broad focus short term dynamic psychotherapy; Strupp: TLDP, Time limited dynamic psychotherapy; Luborksy: Supportive-expressive psychoanalytic psychotherapy; Klerman: Interpersonal psychotherapy; Beck: Cognitive therapy. After a cross-comparison arguments are given why there is still a need for a more problem- and patient-oriented, eclectic and limited psychotherapy. Besides theoretical reasons there are practical and didactic aspects in favour of such a method. PMID- 2192386 TI - [Problem oriented therapy. A new therapeutic and didactic concept]. AB - Problem Oriented Therapy (POT) is a short-term therapy concept that is characterized by the following essentials: Problem orientation, patient orientation, eclecticism and process-structuring. These essentials will be explained and their therapeutic and didactic implications shown. POT is not committed to a certain psychotherapeutic school but uses selectively reliable methods from different therapeutic approaches. The indication to specific therapeutic strategies is made from a pragmatic point of view on the level of problem definition and takes account of the patient's own comprehension of the problem. Transparency and flexibility of therapeutic thinking and acting are essential in POT. This will be illustrated by a case report. The training settings of POT will also be briefly described. PMID- 2192387 TI - [The value of subjective illness theories in problem oriented therapy]. AB - Subjective illness concepts mean the more or less comprehensive psychological explanations about causes and functions of actual psychosocial problems by the patient. These concepts historically arise from interactions with the social environment. In respect to the actual situation they are constructed in a new way. They aim at monitoring the individuals' experience of being ill or healthy. Often they don't accomplish this aim because they are deficient for many reasons. In the therapeutic situation the patient is confronted with the scientific theories of his therapist. Both concepts represent different perspectives of the same problem. However, both have to be discussed in a cooperative manner and ultimately result in a complementary view which we denote as an important issue for our problemoriented therapy. PMID- 2192388 TI - [Standardization of documentation of whole body irradiation--the present situation in the German Society for Medical Physics]. PMID- 2192389 TI - Experiences in the field of elemental analysis in vivo. AB - In this paper some radioanalytical methods will be described for assessing the contents of various elements in the human body. In vivo methods are necessary for this problem. Protein content can be estimated by means of in vivo measurements of nitrogen, bone minerals by means of the total body content of calcium. Fat contains a high concentration of carbon. Carbon in fat can be estimated and from this the total body fat can be calculated. Toxic elements such as lead, cadmium and mercury are assessed by in vivo measurements, both related to occupationally exposed workers and to members of the public. PMID- 2192390 TI - [CT-guided percutaneous biopsy in orthopedics. Indications--planning--technic- personal experiences, with special reference to the spine]. AB - Computed tomography, though few previous reports have dealt with this aspect of it, is an excellent aid when percutaneous skeletal biopsies have to be taken, especially in critical skeletal regions. Our own series consists of 48 CT-guided musculoskeletal biopsy procedures, mainly concerning the spine and pelvis. We used biopsy needles with calibers between 22 G and 14 G; specifically, the sure cut needle was used in most cases. There were no complications. The results were conclusive in 29 cases, semiconclusive in 10 cases, and inconclusive in 9 cases. The advantages of CT guidance are most obvious in the case of lesions of the axial skeleton and pelvis: it allows precise planning of an adequate biopsy approach, better location of small cortex leaks for intraosseous entry of the puncture needle, and more sensitive selection of the best place for tissue sampling. Therefore, with CT guidance intraosseous lesions are more accessible, even to less highly invasive instruments. The risk of complications is low, and the accuracy similar to that obtained with fluoroscopic guidance. PMID- 2192391 TI - [A supratentorial hemangioblastoma]. AB - A case of supratentorial hemangioblastoma combined with two hemangiomas of the liver without manifestation of von Hippel-Lindau disease is presented. The cerebral cystic hemangioblastoma was localized in the right parietal lobe and contained a calcified area but no visible mural solid nodules. The CT and MRT differential diagnosis (arachnoidal cyst, glioma, Echinococcosis, hamartoma and metastasis) is discussed, and the literature on the subject is reviewed. PMID- 2192392 TI - Physiological and pharmacological comparisons of angiotensin II receptors in neuronal and astrocyte glial cultures. PMID- 2192393 TI - Dopamine uptake: a review of progress in the last decade. PMID- 2192394 TI - The regulation and modulation of pH in the nervous system. PMID- 2192395 TI - Neuropharmacological profile of V-9-M, a putative neuropeptide derived from procholecystokinin. AB - (1) The present review suggests that V-9-M, a putative neuromodulator derived from pro-CCK, possesses apparent sedative actions and prevents experimental amnesia in both passive and active avoidance paradigms in rats. (2) These properties are similar to CCK-8, but some differences were noticed; (i) CCK-8 is a potent appetite inhibitor, while V-9-M does not affect food intake in fasted rats, and (ii) small doses of apomorphine cause hypomotility which is abolished by CCK-8, while V-9-M decreases the motility further. (3) More important is the fact that peripheral administration of CCK-8 produces central actions, but that of V-9-M is ineffective. (4) Although CCK-8 and V-9-M are derived from the same pro-CCK, their chemical structures are quite different, and the receptors for these two peptides are not the same. (5) CCK-8 has both central and peripheral receptors, but the presence of a peripheral receptor for V-9-M is questionable. (6) The different properties may be partially explained by this. (7) However, immunochemical studies indicated the coexistence of CCK and GABA in the cortical neurons. (8) This suggests that V-9-M may be present in the GABA neurons together with other CCK fragments. (9) There might be close interaction between V-9-M and the GABAergic system. PMID- 2192397 TI - [Slow virus, prion and nervous system]. PMID- 2192396 TI - [Muscular dystrophy]. PMID- 2192398 TI - [Value of ultrasonography for the diagnosis of cholelithiasis in light of surgical verification]. AB - Up to the age of ultrasonography the cholelithiasis diagnostics has been based on the radiologic examination that is on the peroral cholecystography introduced by Graham and Cole in 1924 as well as on the intravenous cholangiography performed for first time by Langecker and Harwat in 1952. During last years the cholelithiasis diagnostics is more and more frequently based on the ultrasonographic examination. The purpose of this study was in evaluation of ultrasonography in detection of cholelithiasis. The diversity of ultrasonographic images according to the cholelithiasis type and the accompanying alterations in the wall and surrounding area of the gallbladder has been taken into account. The USG diagnostic value and that of routine radiologic methods in diagnosis of cholelithiasis has been additionally compared. PMID- 2192400 TI - [Dermatologic surgery--the possibilities of applying surgical methods to the treatment of skin diseases]. PMID- 2192399 TI - [Selected problems of diagnosis, natural course and prognostic value in borderline hypertension. New directions for research]. PMID- 2192401 TI - [Campylobacter pylori and its role in the etiopathogenesis of upper digestive tract diseases]. PMID- 2192402 TI - [Anti-atherosclerotic properties of calcium antagonists]. PMID- 2192403 TI - [Trials of laryngeal tuberculosis treatment with cantharidin in the past century]. PMID- 2192404 TI - [Ropivacaine--a new local anesthetic with specific properties]. AB - Ropivacaine is the (S)-enantiomer of 1-propyl-2',6'-pipecoloxylidide. In terms of its physicochemical properties, it is a long-acting local anesthetic (molecular weight of the base 274, pKa 8.07, protein-binding 92%). It shows a selective action on A delta and C fibers. This may be attributable to its relatively low partition coefficient (6.1 in n-heptane). The subcutaneous and intravenous acute toxicity (LD50) is lower than that of other long-acting local anesthetics. Because of its vasoconstrictor potency, its use as a vasoconstrictor-free solution is of particular interest. PMID- 2192405 TI - [The equipotency of ropivacaine, bupivacaine and etidocaine]. AB - Ropivacaine, congenerate to bupivacaine and mepivacaine has been widely studied in laboratory animals, but there have been few investigations of its efficacy in human epidural anesthesia and peripheral nerve blocks. The aim of this study was to compare the three long-acting local anesthetics (bupivacaine 0.75%, ropivacaine 1% and etidocaine 1%) and to try, with reference to previous studies, to make some statement about the equipotency of ropivacaine relative to bupivacaine and etidocaine. METHODS. In a double blind randomized study, epidural anesthesia was carried out with 20 ml bupivacaine 0.75% (n = 24) and ropivacaine 1% (n = 21). Following this study epidural anesthesia was carried out with 20 ml etidocaine 1% (n = 20) in an open study. Patients with ASA I or II were enrolled in the study. All patients were scheduled for varicose vein stripping. Male and female patients aged 18-70 years and weighing 50-100 kg were included in the study. Patients were all placed in a sitting position, after which the epidural space was identified by the "loss of resistance" technique and a midline approach, at the L-3/4 interspace. Injections of 3 ml of the local anesthetic were given, followed by the remainder of the local anesthetic at 10 ml/min 1 min later. Following injection patients were immediately positioned supine. Analgesia was determined by the pin-prick method and motor blockade was assessed according to the Bromage scale. Heart rate and blood pressure were monitored until 3 h after injection. RESULTS. The latency of analgesia for the first blocked segment (T 12 for bupivacaine and ropivacaine and L-1 for etidocaine) was 6.0 min for bupivacaine 0.75, 5.5 min for ropivacaine 1%, and 5.2 min for etidocaine 1%, and the highest thoracic dermatome (T 5 for bupivacaine, T 4 for ropivacaine and T 7 for etidocaine) was reached after 24 +/- 10, 26 +/- 9, and 30 +/- 18 min for bupivacaine, ropivacaine, and etidocaine, respectively. The duration of sensory anesthesia at the T 10 dermatomal level was 257 +/- 102, 278 +/- 67, and 191 +/- 86 min for bupivacaine, ropivacaine, and etidocaine, respectively. The two segment regression time was 199 +/- 80 min for bupivacaine, 201 +/- 52 min for ropivacaine, and 174 +/- 81 min for etidocaine. The total duration of sensory block was 340 +/- 103 min for bupivacaine, 428 +/- 65 min for ropivacaine and 223 +/- 62 min for etidocaine, respectively. In the ropivacaine and bupivacaine groups sensory anesthesia was considered adequate for surgery in all cases but one in each group; in the etidocaine group, however 60% of the patients showed inadequate analgesia and all these patients (12/20) required additional analgesics. Bupivacaine achieved an average of motor block 2.1, ropivacaine 2.3, and etidocaine 2.4. CONCLUSION. The results of this study indicate that ropivacaine is an effective local anesthetic agent. Its potency is about equal to that of bupivacaine and much higher than that of etidocaine... PMID- 2192406 TI - [Postoperative peridural analgesia via catheter following abdominal surgery. Peridural bupivacaine versus buprenorphine]. AB - Seventy-five patients scheduled for major abdominal operations were randomly divided into four groups, each with a different postoperative analgesic regime. Group I: buprenorphine 4 micrograms/kg was injected i.v. every 4 h. Groups II-IV: all patients were preoperatively supplied with a thoracic epidural catheter that, however, was not used during the operation. Group II: bupivacaine 0.15 ml/kg was injected epidurally every 2 h, the first dose being 0.5%, the top-ups 0.25%. Group III: buprenorphine 4 micrograms/kg in 10 ml saline was given via the catheter and repeated on request. Group IV: these patients received a combined regime. Bupivacaine was injected as in group II, and in addition buprenorphine was added epidurally in the doses and time intervals of group I. After extubation the patients categorized the intensity of postoperative pain twice, first while lying immobile and then after coughing vigorously, using a rating scale with pain scores from 0 to 10. Thereafter, the analgesic regime described above commenced. One hour later the patients' pain scores were again determined. In addition to pain scores, heart rate (HR), mean arterial pressure (MAP) and paCO2 were recorded at the same points in time. The investigation was then interrupted overnight. The analgesic regime continued as described for groups I and II. Patients in group III received 0.15 mg buprenorphine on request i.v., and in group IV bupivacaine was given as in group II with no further buprenorphine. The study recommenced the next morning at 7:00 a.m. After the initial values (pain scores, HR, MAP, paCO2) had been recorded the analgesic program, as scheduled for each patient, restarted. In group IV buprenorphine was again added to bupivacaine and repeated every 4 h, whereas bupivacaine was injected every 2 h. All values were registered hourly until 7:00 p.m., when the investigation was terminated. RESULTS. On the day of operation and during the first few hours on the morning thereafter, analgesia in groups II and IV was considerably better compared to groups I and III (P less than 0.001). We could not statistically demonstrate, however, that analgesia in group IV was superior to that in group II despite the fact that pain scores were lowest in this group, with a median at rest of 0 throughout the study time. In group III (n = 20), epidural buprenorphine failed to produce any acceptable analgesic effect in 6 patients despite correct catheter position. For this reason they were dropped from the study. No patient in any of the other groups, however, was dropped (P less than 0.01). Later in the 1st postoperative day analgesia in groups II and IV lost its superiority at rest, but coughing continued to be less painful in comparison to groups I and III. We noticed that the duration of action of 0.25% bupivacaine, injected as a bolus, was considerably shorter than expected (less than 2 h) and that several patients experienced pain before the next top-up was given... PMID- 2192407 TI - [The function of the sympathetic nervous system and its behavior during regional anesthesia]. AB - The activity of the sympathetic nervous system is of fundamental importance in the regulation of vital bodily functions. Impairment of sympathetic neuronal efferences results in considerably disordered effector function, and in some cases even in complete failure. Clinically, this is of great significance, because if an anesthetic agent produces cause the sympathetic system to block, the effects can be serious in individual cases, particularly on the cardiovascular system. If complications are to be avoided, it is essential to assess the degree of block correctly. Clinical monitoring has a variety of applications, a particularly useful one being measurement of the sympathetic system during regional anesthesia, for which quantification of the blocking effect is a clinical necessity and the degree of block needs to be ascertained without delay, for example in the case of spinal or peridural anesthesia. The activity of the sympathetic system can be monitored indirectly by two means: by measuring changes in skin temperature (with reference to all circulatory parameters), as these reflect its influence on the arterioles, and by measuring the skin resistance caused by the eccrinal sweat glands, which are also regulated by the sympathetic system. As the anatomical and functional structure of the system is highly complex a connection between the two measurements cannot necessarily be assumed. The two variables were measured simultaneously during spinal anesthesia and analysed. It was shown that the two measurements correlated well, at least in the statistical middle range, and that skin resistance was by far the faster and more sensitive of the two. PMID- 2192408 TI - [Primary pyomyositis in mild climates. Presentation of 2 new cases]. AB - Pyomyositis is an acute bacterial infection which affects striated muscles. It is a relatively rare process in mild climates. Staphylococcus aureus is responsible for 90-95% of cases. Klebsiella pneumoniae pyomyositis is extremely rare with only one other case reported in a mild climate. Two new cases of pyomyositis are described one caused by K. pneumoniae, increasing thus the etiology spectrum in our country, and the other caused by S. aureus ending in fatality, with two focus of pyomyositis (one of which was chronic) and multisystemic secondary affectation. We highlight the appearance of this process in our environment and the necessity to keep it in mind when making a differential diagnosis in order to recognize it and treat it as soon as possible since its prognosis depends on the moment the diagnosis is made. PMID- 2192409 TI - [Diet and non-insulin-dependent diabetes mellitus: historic and current perspectives]. AB - A great majority of patients suffering non insulin dependent dependent diabetes mellitus (NIDDM) can be efficiently controlled with diet, not requiring oral antidiabetic drugs or insulin. The main objective, given the tight relationship between obesity and this type of diabetes, is to decrease caloric intake as well as reducing the amount of saturated fats from the diet in an attempt to delay the onset of cardiovascular manifestations of the disease. Accumulated experience suggests that an increase in carbohydrate intake (60% of the diet) most of which should be food rich in fiber should be recommended given the proven efficacy in improving the control of in blood sugar and lipids. We advocate on the consumption of dry vegetables, and we think that this different attitude in their use is of major importance in NIDDM. PMID- 2192411 TI - Review of hematologic effects of erythropoietin. PMID- 2192410 TI - [Treatment of cancer of the ovary in advanced stages (III and IV)]. PMID- 2192412 TI - Changes in quality of life and functional capacity in hemodialysis patients treated with recombinant human erythropoietin. The Canadian Erythropoietin Study Group. PMID- 2192413 TI - Rate of progression of chronic renal failure in predialysis patients treated with erythropoietin. PMID- 2192414 TI - Early intervention with recombinant human erythropoietin therapy. PMID- 2192415 TI - Recombinant human erythropoietin in the diabetic patient. PMID- 2192416 TI - Seizures and hypertension events. PMID- 2192417 TI - Recombinant human erythropoietin and renal transplantation. The Canadian Erythropoietin Study Group. PMID- 2192418 TI - Recombinant human erythropoietin patient dosing algorithm. PMID- 2192419 TI - [Replantation of limbs and limb extremities]. PMID- 2192420 TI - [Epidural neurostimulation for severe arteritis of the lower limbs]. PMID- 2192421 TI - [History of medicine. The horn of the unicorn]. PMID- 2192422 TI - Exercise and mental health. Beneficial and detrimental effects. AB - Physical exercise is increasingly being advocated as a means to maintain and enhance good mental health. In general, findings from research indicate that exercise is associated with improvements in mental health including mood state and self-esteem, although a causal link has not been established. Research on acute exercise indicates that 20 to 40 minutes of aerobic activity results in improvements in state anxiety and mood that persist for several hours. These transitory changes in mood occur in both individuals with normal or elevated levels of anxiety, but appear to be limited to aerobic forms of exercise. In the case of long term exercise programmes, improvements in the mental health of 'normal' individuals are either modest in magnitude or do not occur, whereas the changes for those with elevated anxiety or depression are more pronounced. Evidence from studies involving clinical samples indicates that the psychological benefits associated with exercise are comparable to gains found with standard forms of psychotherapy. Hence, for healthy individuals the principal psychological benefit of exercise may be that of prevention, whereas in those suffering from mild to moderate emotional illness exercise may function as a means of treatment. Exercise may also result in detrimental changes in mental health. Some individuals can become overly dependent on physical activity and exercise to an excessive degree. This abuse of exercise can result in disturbances in mood and worsened physical health. In the case of athletes the intense training, or overtraining, necessary for endurance sports consistently results in increased mood disturbance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2192423 TI - The sexual response as exercise. A brief review and theoretical proposal. AB - The sexual response is a form of exercise which has strong biological and evolutionary components. Few studies have focused upon sexual behaviour as exercise and the reasons for this are considered. Current information and leads for future study come from animal research. Some historical precursors to modern sex researchers did more to mislead than to advance knowledge but Kinsey and Masters & Johnson set the stage for modern knowledge and applications. There are parallels between the orgasmic response and exercise. Physiological bases of the sexual response help to explain individual differences in sexual behaviour and the well-being that often accompanies states of passionate love, addiction and exercise. Studies suggest that sexual activity is associated with well-being and longevity, yet many health and exercise professionals fail to take account of sexual activity in advancing exercise programmes and executing studies; that is, the so-called Ostrich Effect persists. Investigators need to separate the passionate love stage of relationships which are biologically based and last 3 to 4 years from the later stages of long term committed partnerships in which sexual activity continues as a form of exercise, competence expression and fun. PMID- 2192424 TI - The psychological benefits of exercise and the treatment of delinquent adolescents. AB - The conviction that athletic participation imparts desirable educational, social and personal values has been the basis for including recreational sports in the remedial programme for juvenile delinquents. More recently, the psychological benefits of aerobic exercise and increased fitness have been investigated. Changes following intensive exercise include reductions in anxiety, tension and depression, and increased self-esteem. These effects have been variously hypothesised as due to a sense of increased control or mastery, a meditative effect or to alterations in neurotransmitter-levels. Delinquent adolescents comprise a heterogeneous population characterised by clusters of risk factors, handicapping conditions and psychopathology, with a prevalence of depression and low self-esteem far exceeding that of the population at large. Intervention which can benefit these characteristics may be especially useful in preventive or therapeutic programmes in this group. While less intensive recreational play or physically challenging 'Outward Bound' programmes can be effective in improving social attitudes and self-esteem, intensive aerobic exercise may produce greater improvements in self-esteem and depression. Future research must identify the mechanisms by which exercise confers these benefits, whether it enhances other areas, such as social skills or academic performance, and which populations are benefitted by such programmes. PMID- 2192425 TI - The psychological effects of sports injuries. Coping. AB - Epidemiological reports of sports injury confirm a high incidence of injuries occurring at all levels of sport participation, ranging in severity from cuts and bruises to spinal cord injury. The psychosocial dynamics accompanying sport injury should be known to ensure psychological recovery, an important aspect in rehabilitating the injured athlete. Earlier studies demonstrating psychological differences between athletes and nonathletes indicated the need for actual research on the athlete's postinjury response in lieu of accepting the hypothesis that the emotional responses of athletes to injury parallels existing (i.e. terminally ill) 'loss of health models'. Recent research has shown that injured athletes experience simultaneous mood disturbance and lowered self-esteem. Due to a paucity of research on the coping methods of injured athletes, studies involving the coping methods of several nonathletic patient populations were reviewed. These patients benefitted primarily from a concrete, problem-focused, behaviourally orientated programme which minimises uncertainty. This approach is theoretically ideal for injured athletes, congruent with the goal setting and performance outcome emphasis common to exercise and sport training programmes but to date the effectiveness of these strategies for injured athletes have not been fully examined. Therefore, until such research is available, these coping strategies (also used for performance enhancement) are provided as therapeutic guidelines for dealing with the emotional distress experienced by injured athletes. Individual responses of injured athletes varied from those who took injury in stride to those who required psychiatric intervention. This marked individual variation in response underscores the importance of neither assuming mood disturbance nor overlooking a serious emotional response in the injured athlete. Awareness of the emotional responses of athletes to injury and employment of appropriate coping strategies should facilitate optimal rehabilitation and return to sport. PMID- 2192426 TI - Clinical issues and treatment strategies in stress-oriented athletes. AB - Psychological stress disorders in athletes have become an increasingly important area of study within the last decade as a result of added interest in sports psychology. Scientific inquiry into the impact of life stress events on the health of athletes has only recently been the focus of clinical study. At the forefront of today's understanding of stressful events and its impact on the human organism are a variety of theories which argue either that: stress lies within the environmental input; that it is the cognitive appraisal; that it lies toward environmental input; or that it is a multivariant, multiprocess system that views no single variable or process as the aetiology or psychopathology in the organism. Within the framework of sports medicine, it is seen rather as a complex system of variables that address the environment, the personality of the athlete and the impact of stressful life events on both. PMID- 2192427 TI - Benefits of exercise for the treatment of depression. AB - In general, depressed patients are physically sedentary. They have reduced physical work capacity but normal pulmonary function compared with the general population. This indicates that the reduced fitness level is caused by physical inactivity and is a strong argument for integrating physical fitness training into comprehensive treatment programmes for depression. Exercise is associated with an antidepressive effect in patients with mild to moderate forms of nonbipolar depressive disorders. An increase in aerobic fitness does not seem to be essential for the antidepressive effect, because similar results are obtained with nonaerobic forms of exercise. More than half of the patients continue with regular exercise 1 year after termination of the training programmes. Patients who continue to exercise tend to have lower depression scores than the sedentary ones. Patients appreciate physical exercise, and rank exercise to be the most important element in comprehensive treatment programmes. Exercise seems to be a promising new approach in the treatment of nonbipolar depressive disorders of mild to moderate severity. PMID- 2192428 TI - [The "white plague", point of departure for pulmonary surgery]. PMID- 2192429 TI - Computer detection and analysis of periodic movements in sleep. AB - Standard polysomnography (PSG) and electromyographic (EMG) recording of the right and left anterior tibial muscles by Medilog 9000 recorder was carried out in 10 patients with periodic movements in sleep (PMS). The analog EMG signals and the sleep data from the Oxford ss90III sleep stager were fed into an IBM compatible personal computer for automatic detection and analysis using specific criteria to define the leg events, the interevent interval, the number of epochs (greater than 30 jerks), and the number of bursts (4 to 29 jerks). The results of automatic analysis were compared with data obtained from visually scored paper PSG. The total number of leg jerks detected by visual scoring was 2,812 and by automatic scoring was 2,789. The mean duration of the leg jerks 2.77 s [standard deviation (SD), 1.22] and the mean inter-interval event duration was 27.3 s (SD, 14.7). The total numbers of epochs scored visually was 35 and scored automatically was 33. The correlation co-efficient to the line of identity was 0.8 (p less than 0.005). The sensitivity of automatic scoring was 94% and the specificity was 85%. Automatic detection and analysis of PMS can provide an objective method for the study of several aspects of this disease that are still not yet fully understood. PMID- 2192431 TI - New developments in noninvasive diagnosis of deep vein thrombosis of the lower limbs. AB - Since the clinical diagnosis of deep vein thrombosis (DVT) of the lower limbs is nonspecific, a confirmation by objective tests is mandatory. Recently, three new simple and reproducible methods of detecting DVT have been developed: computerized impedance plethysmography, standardized Doppler ultrasound, and compression ultrasonography. In three large prospective studies including consecutive outpatients with clinically suspected DVT, these tests were blindly evaluated versus phlebography, to determine diagnostic criteria and accuracy. The sensitivity for proximal DVT was 91% for computerized impedance plethysmography, 91% for standardized Doppler ultrasound and 100% for compression ultrasonography; sensitivity for all thrombi (including calf-vein thrombi) was 86, 85 and 91%, respectively; the specificity was 94% for computerized impedance plethysmography, and 99% for both standardized Doppler ultrasound and compression ultrasonography. The results of these studies demonstrate that all the three tests are highly specific and sensitive methods for the diagnosis of proximal DVT in symptomatic outpatients. However, isolated calf thrombi could not be detected adequately. Before these simple tests can be recommended as substitutes for phlebography, the safety of withholding anticoagulant therapy in patients with repeated normal tests should be assessed. PMID- 2192430 TI - Immunohistopathogenesis of persistent generalized lymphadenopathy in HIV-positive patients. AB - Persistent generalized lymphadenopathy (PGL) is a reactive lymphadenitis affecting HIV-positive patients; furthermore, PGL is often a prodrome of AIDS related complex and AIDS. In the present review the authors describe the histology and the immunohistochemistry of lymph nodes of patients affected by PGL. Histologic alterations of lymph nodes with PGL are classified according to three main types: follicular hyperplasia without or with follicular fragmentation, follicular involution and follicular depletion. Immunohistology demonstrates a peculiar infiltration of CD3+/CD4+ and CD3+/CD8+ lymphocytes in germinal centers; CD3+/CD8+ are often grouped in small clusters centered by a newly formed small blood vessel. Accessory follicular dendritic reticulum cells (FDRCs) of germinal centers are characterized by a positive staining for p24 and p19 HIV major core antigens. In germinal centers, FDRCs undergo progressive lysis in follicular involution and in follicular depletion. Other viral antigens, such as EBV, are infrequently seen in lymph nodes from HIV-positive patients. Paracortical areas of lymph nodes are often characterized by prominent postcapillary venule proliferations and by hyperplasia of the endothelial cells which are HLA-DR positive, often p19 and p24 positive, and occasionally express HIV genome. In conclusion, in PGL the histologic changes correlate well with the immunohistologic features; accordingly, PGL might be considered the result of abnormal immune reactions to several stimuli still incompletely known. PMID- 2192432 TI - Detection of hepatitis B virus DNA in serum by spot hybridization technique: sensitivity and specificity of radiolabeled and biotin-labeled probes. AB - The detection of serum hepatitis B virus (HBV) DNA in 32 chronic HBsAg carriers was performed by spot hybridization technique using both biotinylated and radiolabeled probes, in order to compare their specificity and sensitivity. Our results show that both assays are specific since neither evidence of cross hybridization between HBV DNA and sera from patients with chronic non-A, non-B (NANB) hepatitis was found, nor HBV DNA was detected both in patients with chronic anti-HBs/anti-HBc-positive hepatitis and in patients negative for all HBV markers. An agreement between the two assays was observed in 94% of the tested sera. Even though in 5 serum samples (6%) low levels of HBV DNA (0.1-1 pg/100 microliter) remained undetected using the biotin-labeled probe, the lower detection limit of the two assays (0.1 pg of HBV DNA) was the same using purified Dane particles as control. This study indicates that the enzymatic detection of HBV DNA is suitable for routine and rapid monitoring of HBV replication in both HBeAg- and anti-HBe-positive patients, as well as for a semiquantitative analysis of serum HBV DNA. PMID- 2192433 TI - Adoption and validation of the international normalized ratio for monitoring oral anticoagulant therapy: the situation in 1989. AB - The INR/ISI system has been validated in multicenter trials. The system provides a reliable scale for the intensity of oral anticoagulation. It has been recognized that the ISI is slightly dependent on the instrument used for prothrombin time determination. External quality assessment (EQA) of the INR in national programs should be stimulated. EQA results suggest that the precision of the INR can be improved. Many physicians prescribing coumarin congeners are not familiar with the INR system. Improvement of the situation can only be achieved by continuous education. PMID- 2192434 TI - [Insulins]. PMID- 2192435 TI - Presence of human 65 kD heat shock protein (hsp) in inflamed joints and subcutaneous nodules of RA patients. AB - Monoclonal antibodies to the human homologue of the bacterial 65 kD heat shock protein (hsp) were used to investigate the tissue distribution of endogenous hsp 65 in normal versus rheumatoid synovial tissue, in subcutaneous nodules of patients with rheumatoid arthritis (RA) and in several instances of non rheumatoid inflammation. A strong reactivity of the anti-hsp antibody was found in the cartilage-pannus junction in rheumatoid joints and in rheumatoid nodules, but not in normal joints or in normal or inflamed kidney or liver (irreversible graft rejection, chronic glomerulonephritis or primary biliary cirrhosis). The findings provide a new hypothetical explanation for a role of T cells reactive with the 65 kD hsp in the generation of both articular and extra-articular lesions in chronic rheumatoid arthritis. PMID- 2192436 TI - Lymphocytic antigen receptors transmit positive signals! PMID- 2192437 TI - The involvement of Kupffer cells in the clearance of high molecular weight rat IgA aggregates in rats. AB - In the present study the clearance kinetics and tissue distribution of aggregated 125I-labelled monoclonal rat IgA [( 125I] AIgA) of different sizes were studied in rats. Soluble [125I]AIgA disappeared from the circulation in a biphasic manner with an initial rapid distribution half-life (T1) and a second slower half-life (T2). T2 was directly related to the size of the aggregates. High molecular weight [125I]AIgA, containing 10-12 IgA molecules per aggregate [( IgA]10-12), was cleared much faster than low molecular weight aggregates. The main site of clearance was the liver. The larger the size of the AIgA, the more degradation products were found in the circulation. After injection of [IgA]10-12, non parenchymal cells (NPC) contained three times more radioactivity than parenchymal cells (PC) (NPC:PC ratio 3.06 +/- 0.96). Ratios of 0.82 +/- 0.03 and 0.62 +/- 0.12 were observed when [IgA]5-6 and [IgA]2 were injected respectively, suggesting a greater role for Kupffer cells in the clearance of large-sized IgA aggregates. Kupffer cells were shown to be the main cells for localization of large-sized AIgA established by immunohistochemical staining on liver cryostat sections. PMID- 2192438 TI - RT7-defined alloantigens in rats are part of the leucocyte common antigen family. AB - Haemopoietic cells carry a variety of cell-surface molecules, some of which are known to have allotypic variation. In rats, the RT7 alloantigenic system has been well documented using alloantisera. We have produced the first mouse hybridoma cell line secreting an antibody, HIS41, which binds to leucocytes of rat strains carrying the RT7.2 but not the RT7.1 determinant. An IgG2b isotype switch variant (HIS41.2b) of the original HIS41 (IgG1 isotype) was also made. HIS41 showed a clear and discrete binding in immunofluorescent and histological experiments and has already been used in several studies on haemopoietic cell turnover and differentiation employing PVG rats congenic for RT7. The present study addresses the question of whether the RT7 gene products are members of the L-CA family, which has been a matter of controversy over the last decade. When using HIS41 for the analysis of tissue distribution and molecular weight of RT7 gene products, a strong similarity was evident with the data reported for the L-CA detected by MRC OX-1 and MRC OX-30. These two MoAb have been reported to bind to all members of the L-CA family. All haemopoietic cells, excluding erythrocytes and the more mature stages of erythropoiesis, stained with HIS41. The molecular weights of HIS41 binding molecules on thymocytes and peripheral T cells were comparable to the L-CA precipitated by MRC OX-1. Capping and sequential immunoprecipitation studies indicated that HIS41 and MRC OX-30-binding molecules were identical. MRC OX-1, however, appeared to bind only a subset of these molecules. Thus, our study confirms the identity of RT7.2 gene products and L-CA. It also revealed a difference between MRC OX-1 and MRC OX-30 not noticed previously. PMID- 2192439 TI - Epithelioid angiomatosis or cat scratch disease with splenic and hepatic abnormalities in AIDS: case report and review of the literature. AB - Cat scratch disease (CSD) in the setting of HIV infection is associated with lesions of epithelioid angiomatosis but not with granulomatous lesions seen in the normal host. We report a case of CSD in a patient with AIDS and Kaposi's sarcoma with epithelioid angioma of skin, thrombocytopenia, and abnormalities of liver, spleen, lymph node, and pleura that responded to antimicrobial therapy. We also review reported cases of epithelioid angiomatosis in HIV infections. 12 of these resolved, including 3 without antimicrobial therapy; 18 demonstrated pleomorphic organisms with Warthin-Starry silver stain. Six involved visceral or bony as well as skin lesions. CSD should be considered in the setting of HIV infection with skin nodules even in the presence of biopsy-proven Kaposi's sarcoma. CSD may in these patients be responsible for a variety of disseminated lesions which respond to antimicrobial therapy. PMID- 2192440 TI - A randomised comparison of ceftazidime and piperacillin, both in combination with flucloxacillin for treatment of febrile episodes in neutropenic children. Finnish Three-Centre Study. AB - 111 febrile episodes in 98 neutropenic children were randomly treated with either ceftazidime (CAZ) 150 mg/kg/day or with piperacillin (PIP) 200 mg/kg/day, both combined with flucloxacillin (FLUC) 50 mg/kg/day. A total of 37/47 (79%) eligible episodes in the CAZ group and 41/53 (77%) in the PIP group were cured without needing to stop the initial therapy. The success without modification of the treatment in the verified septicaemias in the CAZ group was 8/18 (44%) and in the PIP group 5/18 (28%). Of the bacteriologically documented infections, 13/24 (54%) in the CAZ group and 11/24 (46%) in the PIP group were cured without modification of the therapy. Similarly, 17/31 (55%) of all the isolated bacteria in the CAZ group and 14/33 (42%) in the PIP group were eradicated with the initial therapy. Overall there were 13 deaths of which 4 in the CAZ group and 5 in the PIP group occurred during the infection. An increasing granulocyte count exceeding 0.25 x 10(9)/l at the end of the therapy was a good prognostic sign for the outcome of the infection. This study indicates that CAZ is as effective as PIP in the treatment of infections in neutropenic children. PMID- 2192441 TI - Arthritis associated with Strongyloides stercoralis. AB - A case of reactive arthritis combined with uveitis associated with a longstanding and heavy infestation with Strongyloides stercoralis is reported in a 32-year-old HTLV-1 positive West Indian man. Stool examination revealed numerous adult worms and larvae. Treatment with thiabendazole and ivermectin resulted in prompt improvement. PMID- 2192442 TI - Risk of HIV transmission among health care workers: a multicentre study. The Italian Collaborative Study Group on HIV Occupational Risk. PMID- 2192443 TI - Radical prostatectomy as treatment of localized prostatic cancer. Early results, with special focus on transrectal ultrasound for local staging. AB - Radical prostatectomy was performed for localized prostatic cancer on 68 patients (mean age 65 years). Rectal palpation alone was used to determine local operability in the first 38 cases, and its accuracy proved to be 63%. Transrectal ultrasound in conjunction with clinical examination was used instead in the last 30 patients, with 80% accuracy. There was one perioperative death and the total complication rate was 37%. Postoperatively three patients were totally incontinent and five had mild stress incontinence. Of the 29 patients operated on with the nerve-sparing Walsh technique, 11 had penile erections 6 months postoperatively. The mean follow-up time was 34 (4-69) months. Local recurrence or distant metastases were found in 11 cases (16%). In ten of them the primary tumour was locally advanced (pT3 or pT4), and in one it was intracapsular (pT2) but poorly differentiated. Radical prostatectomy is concluded to be safe and its complication rate acceptable. Careful preoperative evaluation of the extent of disease is essential for cure, and transrectal ultrasound increases staging accuracy. PMID- 2192444 TI - Desmopressin: a new principle for symptomatic treatment of urgency and incontinence in patients with multiple sclerosis. AB - Thirteen patients with advanced multiple sclerosis and urge urinary incontinence were treated with desmopressin--a synthetic analogue of antidiuretic hormone--in a double-blind cross-over study. The micturition frequency decreased significantly (p less than 0.05). Less leakage was considered valuable for daily life. Peroral medication was favourable in these patients with muscular dysfunction. Side-effects were few. PMID- 2192445 TI - Captopril treatment in Bartter's syndrome. AB - A 13-year-old girl presented with lassitude, polyuria and hypokalemia. Plasma renin concentration and urinary prostaglandin excretion were elevated, whereas plasma aldosterone concentration, urinary aldosterone excretion and blood pressure were normal. A diagnosis of Bartter's syndrome was made. The result of treatment with oral potassium was unsatisfactory. Treatment with acetylsalicylic acid had some effect, but an allergic reaction rendered withdrawal necessary. Treatment with the angiotensin converting enzyme inhibitor captopril and oral potassium led to clinical and biochemical improvement. PMID- 2192446 TI - Paramedian versus midline incision for the insertion of permanent peritoneal dialysis catheters. A randomized clinical trial. AB - A randomized trial was conducted to examine the influence of the site of catheter insertion on the mechanical complications associated with the use of peritoneal dialysis catheters (pericatheter leakage/herniation and tip migration). 37 patients requiring a dialysis catheter for future CAPD were randomized to insertion by either a midline (prior standard approach) or a lateral incision (new approach). Thirteen catheters (6 midline, 7 lateral) failed for mechanical reasons--mainly irreversible tip migration. The one year estimated catheter survival without mechanical failure was found to be similar in the two groups: midline (59%) and lateral (51%), (0.4 less than p less than 0.5). PMID- 2192448 TI - [Tissue characterization of the liver using ultrasound attenuation in an animal experiment]. AB - Frequency-dependent attenuation of sound is considered a characteristic parameter of the interaction between sound and tissue and has been studied particularly in the liver via many different techniques. Due to the relatively wide scatter of the measured single values, especially in pathological liver samples, a clinically feasible application of the procedure has not yet been found. In the present paper, the suitability of the frequency-dependent coefficient of sound attenuation for tissue characterization with comparable experimental conditions in vitro was tested in a statistically representative collection of histologically defined tissue specimens of rat liver. Several statistical procedures were used (cluster analysis, discrimination analysis). Normal livers can be usually distinguished from pathological specimens by means of the frequency-dependent coefficient of sound attenuation with only slight scatter of the individual values. Although the latter differ on the average from normal specimens, they diverge considerably in respect of single values resulting in significant differences only in case of extensive tissue damage (cirrhosis). On the basis of tissue classifications in clinical and pathological use, only a rough tissue differentiation is possible. By using additional parameters of the interaction between sound and tissue, sonographic differentiation of pathologically changed tissue my be improved. PMID- 2192447 TI - [Computerized ultrasound imaging of the shape of the tongue in forming long vowels in German]. AB - The contours of the tongue during pronunciation of the long German vowels were assessed by ultrasound in 22 healthy volunteers. Using statistical methods, models of the shape of tongue were calculated. These models can be used for clinical diagnosis and bio-feedback therapy in patients with speech disorders. PMID- 2192450 TI - [Intraoperative ultrasound imaging in neurosurgery]. AB - Intraoperative sector scanning enables routine imaging of the entire anatomy of intracranial and spinal spaces. Almost all of the pathological processes are exactly localised. It is an essential preliminary condition that fully sterilizable, handy ultrasound probes of 6 to 10 MHz including an accurate instrument- and puncture guide are available. Initial orientation projections similar to CT- or MRI scans are chosen using defined anatomical "landmarks". Cavities filled with aqueous fluids like ventricles, arachnoidal cysts, cystic low-grade gliomas are shown as regions of low echo intensity. Other pathological processes are usually imaged by their hyperecho-characteristics: brain oedema has an increased reflexion compared to normal brain tissue; all brain tumors are diffusely echogenic, the image allows preliminary grading e.g. of gliomas. Vascular processes like aneurysms and angiomas are well defined by wall- and perfusion characteristics. Ultrasound guiding enables even the most minutely detailed microsurgical approach; cysts and disorders of CSF circulation can be treated by simple ultrasound-monitored catheterization. Even stereotactic biopsy can often be replaced. Complications, such as hemorrhages, are recognised immediately. PMID- 2192449 TI - [Reproducibility of ultrasound criteria for characterizing carotid artery stenoses]. AB - Comparisons with intraoperative findings suggest that Duplex scanning may be of value in predicting the morphology of carotid artery stenoses. Such studies, however, are based on the results obtained by experienced investigators. To clarify whether sonographic criteria can be standardized, 6 investigators from different hospitals each documented 30 carotid artery stenoses of greater than or equal to 40% diameter reduction which could be imaged in at least 2 planes. Three sonographic criteria (plaque surface, echo density, echo structure), each with 8 categories, were assessed from the image documentations by the 6 as well as by 2 independent further investigators. Depending on the experience and on the device used 29-81% of all stenoses greater than or equal to 40% examined in the different laboratories could be included in the study. The +/- 1 category concordance between the different investigators averaged 50-60% for all sonographic criteria independent from the degree of stenosis and from the image quality. Because of lack of sufficient reproducibility the subjective assessment of sonographic criteria is found to be not suitable for use in multicentre studies. PMID- 2192451 TI - [CT/MRI correlated stereometry with ultrasound in brain surgery]. AB - Today the accuracy of medical imaging systems lies between +/- 0.5 mm (CT) and +/ 2.5 mm (MRI). In neurosurgery the overall uncertainty may reach the dimension centimetres. A non-tactile ultrasonic measurement system is described that allows three-dimensional measurement with a theoretical accuracy of +/- 0.1 mm in a frequency range between 50 and 70 kHz. In practice the accuracy is better than +/ 1 mm with a repetition rate of 10 per second for the x,y,z-data sets. PMID- 2192452 TI - [Ultrasound instruments for surgical purposes--technical aspects and selected areas for use]. AB - Surgical instruments simulated to oscillate by means of low-frequency performance ultrasound are particularly useful for specific fields of application. A survey describes the technical principle of action and the development work carried out at the Technical University of Karl-Marx-Stadt in the GDR to produce ultrasound instruments for tumour extraction and aspiration, for the insertion of stomatological leaf implants, for percutaneous lithotrips of kidney stones and for the surface treatment of septic wounds. PMID- 2192453 TI - [Ultrasound criteria of a meniscus lesion]. AB - The tear in the meniscus interrupts the outline at which the sound-wave energy is reflected. This means that the sonogram shows an echo-rich, light reflection pattern. Degeneration also shows up as an echo-rich area, reflecting greater density of the tissue in the meniscus. This has been confirmed by experimental examination of knees of corpses, and also by clinical experience based on more than 2000 sonograms of the meniscus. A quota of more than 90% correct diagnoses can be obtained if the proper criteria are observed in case of a lesion of the meniscus, and if the technical equipment is adequate and the examiner has acquired sufficient skill. PMID- 2192454 TI - [Comparative study of 2 dosage forms of liquid dimethicone for ultrasound premedication]. AB - A double-blind study was carried out to compare the effects of a premedication with 4 x 500 mg dimethylpolysiloxane (DPS)/24 hours and with 2 x 500 mg/12 hours before abdominal ultrasonography. The investigations covered 13 abdominal regions in specified planes. The incidence of the unobscured presentation of the selected organs and organ sections per patient served as a basis for a sonography index. This index was 67%, without significant difference between the two groups. We believe that the optimal conditions for sonography are given when the patient is fasting and two 500 mg doses of DPS are administered, one in the evening before and one in the morning at the day of investigation. PMID- 2192455 TI - Partial symmetrization of the photosynthetic reaction center. AB - The bacterial photosynthetic reaction center (RC) is a pigmented intrinsic membrane protein that performs the primary charge separation event of photosynthesis, thereby converting light to chemical energy. The RC pigments are bound primarily by two homologous peptides, the L and M subunits, each containing five transmembrane helices. These alpha helices and pigments are arranged in an approximate C2 symmetry and form two possible electron transfer pathways. Only one of these pathways is actually used. In an attempt to identify nonhomologous residues that are responsible for functional differences between the two branches, homologous helical regions that interact extensively with the pigments were genetically symmetrized (that is, exchanged). For example, replacement of the fourth transmembrane helix (D helix) in the M subunit with the homologous helix from the L subunit yields photosynthetically inactive RCs lacking a critical photoactive pigment. Photosynthetic revertants have been isolated in which single amino acid substitutions (intragenic suppressors) compensate for this partial symmetrization. PMID- 2192456 TI - Drug-induced myopathies. PMID- 2192457 TI - Pneumatosis cystoides intestinalis in systemic sclerosis and other diseases. PMID- 2192458 TI - Symmetrical erosive disease in Archaic Indians: the origin of rheumatoid arthritis in the New World? PMID- 2192459 TI - Ankylosing spondylitis in women. PMID- 2192460 TI - [Experimental results of biomechanical strength of the meniscus suture in the area of zone II]. AB - The biomechanics of the sutured meniscus were studied in an experimental in vitro assembly. The characteristics of load transmission and changes in radial tensile strength were analyzed under static load conditions. With the knee joint in extension the longitudinally ruptured meniscus presents only slight changes with regard to load transmission and radial stretch. Increased gaping of the anterior horn accompanied by a compensatory radial compression in the posterior segment occurs with flexion and contralateral tibial rotation. Repair of the meniscus results in partial compensation of these phenomena, although both changes are still reproducible to a lesser extent. A vertically applied suture provides more mechanical stability than horizontal fixation. Static weight bearing is of lesser significance in producing separation of the reconstructed meniscus. Postoperative care following meniscus reconstruction must include immobilization, although early weight bearing can be permitted. PMID- 2192461 TI - [Salmonelloses of food origin. Interview by Pierre-Marie Granier]. PMID- 2192462 TI - Growth hormone by daily injection in patients previously treated for growth hormone deficiency. AB - When recombinant-DNA-derived methionyl growth hormone (met-GH) became available for patients resuming treatment, we were able to compare dose intervals in 47 prepubertal children with growth hormone deficiency. Patients were randomly assigned to one or three doses weekly or to daily injections for a total dosage of 0.3 mg/kg weekly. If the patient's annual growth failed to increase more than 2 cm above baseline, the dose interval was changed from weekly to three times a week or from three times a week to daily. In the second year of the study, all patients received daily injections. Despite a mean duration of previous treatment with growth hormone of more than 3 years, daily injections in 16 patients throughout the first year of the study resulted in a mean growth velocity (9.6 +/ 2.4 cm) comparable to that in newly treated patients given met-GH three times weekly in other trials. Administration by daily injection was more effective than injection three times per week (P less than .05) in 13 patients (7.9 +/- 2.1 cm) or once a week in four patients (7.7 +/- 1.2 cm). Second year growth velocities in 21 patients who had received once-a-week or three-times-a-week injections the first year of the study, increased significantly with a change to daily injection (7.7 +/- 2.2 vs 8.8 +/- 1.9 cm) (P less than .05). PMID- 2192463 TI - The three phases of blood pressure in stroke. AB - Studies of three large series of hypertensive patients having strokes have shown that systemic blood pressure responds to stroke during the acute phase. The blood pressure is elevated on the day of admission to the hospital in 82% of patients and then decreases to normotensive levels during the subacute stage in 59%. During the chronic phase of stroke, normal blood pressure persists in 26% of these patients. The three phases of blood pressure change after stroke are likely a physiologic response to ischemia of the brain followed by recovery of brain function. The identification of these three states of blood pressure in stroke underlines the importance of prudence and caution in administering antihypertensive drugs to patients who have had a stroke. PMID- 2192465 TI - Thomas Phaer, MD (1510-1560): father of English pediatrics. PMID- 2192464 TI - The Asclepiads of Dublin: a moment in Ireland's medical history. PMID- 2192466 TI - Stevens-Johnson syndrome after radiotherapy. AB - We have reported a case of classic Stevens-Johnson syndrome in association with treatment using a cobalt radiation therapy unit. Previous reports of such an association have been extremely rare. At the time of the reaction, the patient's only medications were methyldopa and trichlormethiazide. Other drugs in the thiazide class have been associated with such a reaction. We feel this is an unlikely association in our patient, however, because she had been on trichlormethiazide for a number of years. This report suggests the role of radiotherapy as a rare cause of Stevens-Johnson syndrome. PMID- 2192467 TI - Candida albicans infected pseudocyst in a postpartum woman. AB - We have presented the case of a postpartum woman with a pseudocyst infected with C albicans and have reviewed the relevant literature. The patient did well with surgical drainage of the pseudocyst and adjunctive therapy with amphotericin B. Candida species isolated from a pancreatic pseudocyst or abscess should be considered pathogens, and the patient should receive aggressive therapy. PMID- 2192468 TI - Maternal paraparesis after epidural anesthesia and cesarean section. AB - Continuous epidural infusion of local anesthetics containing epinephrine has become increasingly popular. This technique has been associated with few, if any, complications. We have presented a case of anterior spinal artery syndrome with paraparesis after continuous lumbar epidural infusion of an anesthetic during labor and subsequent emergency cesarean section. PMID- 2192469 TI - Invasive pulmonary penicilliosis: successful therapy with amphotericin B. AB - We have described a patient with invasive pulmonary penicilliosis, documented by thoracotomy and cured with amphotericin B. Penicillium sp isolates in immunosuppressed patients should not be disregarded without a thorough investigation, especially if normally sterile sites are involved. Amphotericin B therapy may be successful, especially if accompanied by a reversal or moderation of immunosuppression. PMID- 2192470 TI - Obturator hernia: a difficult diagnosis. AB - We have presented the case of an elderly woman with severe kyphoscoliosis, osteoarthritis and left knee effusion who had symptoms and signs of intermittent intestinal obstruction. Operation showed a left-sided obturator hernia. In any elderly, debilitated, chronically ill woman, symptoms and signs of recurrent small-bowel obstruction (without a history of abdominal surgery or external hernias) and pain along the ipsilateral thigh and knee (Howship-Romberg sign) should raise suspicion for an obturator hernia. If the hernia is not palpable by physical examination, a CT scan of the pelvis and upper aspect of the thigh would confirm the diagnosis before operation and allow prompt treatment and better chance of patient survival. PMID- 2192471 TI - Systemic lupus erythematosus: pulmonary presentation in childhood. AB - Pulmonary symptoms as the initial or primary manifestation of SLE are rare. When pulmonary symptoms are present, they occur most commonly when other organ systems are involved. The absence of skin and renal involvement, the presence of normal serum complement, and the poor response to corticosteroids in this patient are of interest. Pulmonary disease produced by childhood SLE may represent, as in adults, a subgroup of SLE disease. Our report emphasizes the importance of recognizing diffuse interstitial infiltrates as an initial symptom of childhood SLE even in the absence of more obvious signs. PMID- 2192473 TI - [Clinico-experimental basis of phytotherapy of acute dysentery]. PMID- 2192472 TI - Management of hepatic hydrothorax with a peritoneovenous (Denver) shunt. AB - One patient with alcoholic cirrhosis and a massive hydrothorax resistant to medical management and thoracocentesis was treated with a Denver peritoneovenous shunt. This patient's progress has been followed for 14 months and the pleural effusion has not recurred. PMID- 2192474 TI - [Characteristics of the postoperative period in diabetes mellitus type 1 in patients with distal splenorenal anastomosis]. AB - Eight patients with type I diabetes mellitus have been operated on to form a distal splenorenal anastomosis (DSRA). A critical period (the 6th and the 7th days) postoperation has been observed when severe metabolic acidosis develops; to prevent its development, transfusions of 4% sodium bicarbonate solution (1.5 2.01) have been administered before the critical period for 24 hrs, with the metabolic condition monitored by biochemical analyses. Studies of metabolism in these patients after surgery have revealed a complete normalization of the acid base balance and of potassium level, as well as a reduction of the blood glucose concentration. The doses of exogenic insulin have been reduced by 30%, this being associated with a tendency to an increase of the levels of endogenic insulin, C peptide and glucagon of the blood. This helps a better stabilization of the diabetic process after the formation of a DSRA. PMID- 2192475 TI - [Refractory cardiopulmonary insufficiency and peripheral vasodilators]. PMID- 2192476 TI - [Dalargin in the treatment of arteriosclerosis obliterans of the lower extremities]. PMID- 2192477 TI - Intracardiac ectopic thyroid: a case report and review of published cases. AB - A woman with ectopic intracardiac thyroid tissue showing features of a colloid storage goitre presented with ventricular tachycardias and signs of right ventricular outflow obstruction. As the tumour was benign and removed at necropsy, the results of surgery are likely to have been good, but she died from a cardiac arrest before operation. PMID- 2192478 TI - Man-made mineral fibers (MMMF): human exposures and health risk assessment. AB - MMMF are made by spraying or extruding molten glass, furnace slag, or mineral rock. Health concerns are based on the morphological and toxicological similarities between MMMF and asbestos, and the well-documented evidence that asbestos fibers can cause lung fibrosis (asbestosis), bronchial cancer, and mesothelioma in humans. Epidemiological evidence for human disease from inhalation exposures to fibrous glass is largely negative. Some positive associations have been reported for slag and rockwools. Most of the toxicological evidence for MMMF toxicity in laboratory animals is based on non-physiological exposures such as intratracheal instillation or intraperitoneal injection of fiber suspensions. The risks for lung fibrosis, lung cancer, and mesothelioma for industrial exposures to most fibrous glass products are either low or negligible for a variety of reasons. First, most commercial fibrous glass products have mean fiber diameters of approximately 7.5 microns, which results in mean aerodynamic diameters greater than 22 microns. Thus, most glass fibers, even if dispersed into the air, do not penetrate into the lung to any great extent. Second, the small fraction of smaller diameter fibers which do penetrate into the lungs are not persistent within the lungs for most fibrous glass products, due to mechanical breakage into shorter lengths and dissolution. Dissolution is most rapid for the smaller diameters (less than 0.1 micron) capable of producing mesothelioma. The greater hazards for slag and rockwools, in comparison to conventional fibrous glass, appear to be related to their smaller diameters and greater durability within the lungs. PMID- 2192480 TI - Risks associated with indoor infectious aerosols. PMID- 2192479 TI - The risk of nitrogen dioxide: what have we learned from epidemiological and clinical studies? AB - Nitrogen dioxide (NO2) is an oxidant gas which contaminates ambient air in many urban and industrial locations, and indoor air in homes with combustion appliances. The Environmental Protection Agency presently regulates NO2 in ambient air as a "criteria" pollutant. In spite of decades of laboratory, clinical, and epidemiological research, the health effects of NO2 exposure on humans are not well understood. The toxicological evidence suggests that increased susceptibility to infection, functional deficits from effects on airways, and deterioration of the status of persons with chronic respiratory conditions, including asthmatics, are of potential concern. This paper provides a perspective on the present evidence related to human health effects of NO2. It addresses methodological barriers that limit the available data; assesses the adequacy of the data for risk assessment; and proposes a research agenda to obtain needed information on the health effects of NO2. PMID- 2192481 TI - Exposure to man-made mineral fibers: a summary of current animal data. AB - The inhalation of asbestos fibers (crocidolite, chrysotile and amosite) has been implicated in the development of a number of lung disorders including lung cancer, asbestosis, and mesothelioma. The mechanism responsible for these effects is not well characterized but is generally thought to be related to the fibrous nature of these materials. Therefore, concerns have also been raised as to the potential health impact of other fibrous materials including man-made mineral fibers. Man-made mineral fibers are being used as substitutes for asbestos in a wide range of products. However, relatively little data are available on the potential health impact of these fibrous materials. Epidemiology and clinical studies have served as an important source of information on the effect of various environmental pollutants, but have not been sufficient to date to fully address the potential health impact of man-made mineral fibers. This is due in part to the relatively recent introduction of a number of these materials, the long latency period before the onset of clinical symptoms, and in general, the lower exposure levels associated with these materials. Therefore, a number of animal studies have been performed to predict or confirm the toxicity of various man-made mineral fibers in humans. Both fibrosis and mesothelioma have been induced in experimental animals exposed to man-made mineral fibers although no disease has been consistently observed in occupationally exposed workers.2+ While little is known about the mechanism of this response, information from animal and cell culture experiments indicate that dose, fiber dimension, and fiber durability are the most important factors in determining the biological activity of these materials.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2192482 TI - Airborne microbial allergens: impact and risk assessment. PMID- 2192483 TI - Immunological screening of benzodiazepines in urine: improved detection of oxazepam intake. AB - Immunological screening analysis of benzodiazepines in urine using the EMIT (enzyme multipled immuno-technique) and FPIA (fluorescence polarization immunoassay) techniques does not reliably detect the intake of therapeutic doses of oxazepam. In 23 patient urine samples, in which the presence of oxazepam could be verified chromatographically, only about 50% were detected as positive in the immunoassay systems. However, when the screening procedure was modified to include a simple step of hydrolysis of urine using the enzyme beta-glucuronidase to liberate conjugated oxazepam, improved detection of oxazepam intake was achieved. With EMIT 95% and with FPIA 100% of the samples were detected as positive. Since oxazepam arises in vivo also as a metabolite of other common benzodiazepines, the modification will most likely contribute to the generally improved detection of benzodiazepines. PMID- 2192484 TI - Gut associated immune responses in clinical and experimental giardiasis: an overview. AB - Giardia lamblia, the protozoan parasite, first described by Von Leewenhoek in 1681, has come into prominence in last quarter century because of mounting awareness that it may cause significant morbidity and loss of man power. Earlier thought to be a commensal organism, it has been recognised as a true intestinal pathogen in the past three decades. Nevertheless, the mechanism of the disease caused by this protozoan parasite (in the human host's small intestine) continues to remain unexplained. The infection with G. lamblia is worldwide with an average prevalence of 12.5 per cent and is especially common in children and may cause failure of child to thrive. The G. lamblia infection has been implicated in a number of water borne epidemics and is important cause of traveller's diarrhoea all over the world. Infection with G. lamblia may be entirely asymptomatic, may produce a mild, self limiting illness or chronic diarrhoea with or without malabsorption. The reasons for such variations in severity are not clearly understood. However, interplay of virulence of parasite, nutritional status and type of the host immune responses and its effect on intestinal mucosa appear to modulate the infection. PMID- 2192485 TI - [Ozone respiratory toxicity]. PMID- 2192486 TI - [Appendicular mucocele. Clinical--anatomopathologic and therapeutic aspects]. PMID- 2192487 TI - [Role of the family in the psychiatric care of adolescents]. PMID- 2192488 TI - Cell junctions in lymphomas: study of a primary ovarian T-cell lymphoma and review of fifty-six other cases of lymphoma. AB - A case of primary ovarian lymphoma was studied by light microscopy, immunohistochemistry, and electron microscopy. The ultrastructural study revealed the presence of cell junctions of the paired subplasmalemmal densities and tight junctions between adjacent lymphoid cells. Fifty-six cases of non-Hodgkin's lymphoma randomly selected from the files of the Electron Microscopy Facility of the Faculty of Health Sciences, McMaster University, were reviewed. Paired subplasmalemmal densities and tight junctions were identified in five of the cases (9%). This study suggests that the absence of cell junctions should not be considered an essential criterion for the ultrastructural diagnosis of lymphomas. PMID- 2192489 TI - Glial fibrillary acidic protein expression in pleomorphic adenoma of salivary gland: an immunoelectron microscopic study. AB - Previous immunocytochemical studies of pleomorphic adenomas have demonstrated consistent labeling with glial fibrillary acidic protein (GFAP). Cross-reactivity with other intermediate filaments of similar structure and chemical composition has been suggested to account for this seemingly inappropriate pattern of immunoreactivity. To investigate further this phenomenon, we examined five pleomorphic adenomas by immunoelectron microscopy. Ultrastructural features were similar to those described by other investigators, with ductal epithelium being surrounded by myoepithelial cells and modified cells becoming detached to form the isolated stellate and spindle cells of the stroma. As part of this process, many neoplastic myoepithelial cells appeared to lose their specialized ultrastructural features, assuming a rather undifferentiated appearance. Single and double immunoelectron microscopic labeling showed vimentin filaments in all these neoplastic myoepithelial cells. In contrast, GFAP filaments were identified only in the most undifferentiated cells. Such restriction of GFAP filaments to an ultrastructurally definable subset of neoplastic cells provides strong evidence against nonspecific staining due to cross-reactivity. Given the previously described coexpression of vimentin and GFAP by neoplastic cartilage, it appears likely that this immunophenotype in neoplastic myoepithelial cells reflects early chondroid differentiation. PMID- 2192490 TI - [Echocardiographic functional parameters of the left ventricle as a prognostic indicator in coronary heart disease]. AB - The value of two-dimensional cross-sectional echocardiography for the estimation of the left ventricular function had been investigated in 241 consecutive patients with suspected coronary artery disease (CAD). The day before left heart catheterization the left ventricular volumes (EDV, ESV) as well as the global left ventricular ejection fraction (EF) were calculated from the RAO-equivalent in the 2D-echo and in addition the classification of the EF was visually performed from different cross-sections. The coronary angiography showed in 208/241 patients hemodynamically effective stenoses (lumen restriction greater than 50%). For 192/208 patients there were diagnostically usable 2D-echograms as well as clinical data over an observation period of 3 years and 7 months. The 2D echo correspond quite well to the levocardiography for the calculation of the EDV with r = 0.75, with r = 0.85 for the ESV, and with r = 0.80 for the EF. The mere visual evaluation of the EF out of the 2D-echo agreed well in 84% of the cases to the quantitative determination. During the observation period 18/192 patients died; 17/18 of these patients of cardial causes. Out of the patients with normal EF in the 2D-echo only 3.5% died, with slightly reduced EF 10% died. With highly reduced EF mortality was with 40% significantly increased (p less than 0.001). Thus in patients with CAD unfavourable long-time prognosis may be quickly recognized by their markedly reduced left ventricular function in the 2D echocardiogram, which shows favourable correspondence to invasive data. PMID- 2192491 TI - [Angioscopy of the coronary vessels]. AB - Direct visual examination of the interior surfaces of intact human coronary arteries is now a reality, both from intraoperative and transluminal approaches. As an additional investigation to angiography it improves the knowledge about the corresponding morphology of angiographically visible changes. Since the first report about percutaneous and intraoperative coronary angioscopy by Spears et al. in 1982 important indications concerning the intraoperative approach were defined such as the control of coronary atherectomy, intraoperative balloon dilatation and laser angioplasty, the inspection of the grafts prior to implantation and the assessment of the quality of the distal anastomosis after graft insertion. The most important clinical result angioscopy has brought about is the postulation of a concept of the different clinical forms of coronary artery disease based on the morphological stages of atherosclerosis, which were defined by angioscopy and could be related to clinical symptoms. Scientific studies today are concerned with determinants for the patency rate of bypasses, the restenosis rate of PTCA, the acute and chronic effects of drugs, and the mechanism of all kinds of catheter-supported angioplasties. The next important application of coronary angioscopy will undoubtedly be the simultaneous visual control of coronary angioplasty procedures such as laser angioplasty and other new methods. PMID- 2192492 TI - [Improvement of coronary prognosis by reducing LDL-cholesterol]. AB - Elevated LDL-cholesterol levels mean increased risk for coronary heart disease. In different studies the indication for decreasing high LDL-cholesterol in patients with coronary heart disease was proven. This is also the case with patients suffering from high LDL-cholesterol but not yet coronary heart disease. It is supposed that with longer duration of studies the total mortality between verum and placebo groups will also reach significance. PMID- 2192493 TI - Survey of encephalopathy incidence set up by Health ministry. PMID- 2192494 TI - Studies on E coli vaccines: effect of storage on endotoxin content. PMID- 2192495 TI - Seal distemper in Norway in 1988 and 1989. PMID- 2192496 TI - [Metabolic and acid-base changes in intensive diuretic therapy in heart failure]. AB - A group of 65 patients with advanced heart failure was examined with the aim to disclose changes in serum glucose, creatinine, potassium, chloride, and acid-base balance under the influence of intensive diuretic therapy. 50 patients were treated with ordinary furosemide and amiloride combination (average observation time 25 days), in 15 cases amiloride was replaced by captopril 75-150 mg/day (average observation 15.5 days). The results are as follows: 1. We found no rise of glycaemia in non-diabetics with either ordinary diuretic therapy or captopril. On the contrary: stress hyperglycaemia in the beginning of the therapy normalized in the course of it. 2. There was a significant rise of serum creatinine during the first two weeks of therapy with furosemide and amiloride. Reversal of this trend followed after captopril. 3. There was no fall in the average serum chloride concentration during ordinary diuretic therapy. Adding captopril to the regime brought about a rise in serum chloride. 4. Serum potassium had no tendency to fall either after furosemide and amiloride or furosemide and captopril. 5. The acid-base balance showed no shift towards metabolic alkalosis during an intensive but rational diuretic regime either with or without captopril. On the contrary: mild initial metabolic alkalosis had a tendency to normalize with proceeding cardiac compensation. PMID- 2192497 TI - Comparison of bedside methods to assess lung mechanics in ventilated neonates: inflation pressure, amount of ventilation and optical compliance versus measured compliance. AB - Compliance of the respiratory system (CRS) is rarely measured in the critically ill neonate. Instead, inflation pressure (dP), amount of ventilation (dPxfr) and optical CRS are used as indirect parameters to characterize lung mechanics. In 30 randomly chosen newborns ventilated for various causes we investigated which of these bedside methods most accurately represents the compliance of the respiratory system. The correlation coefficient was much higher for the optically determined compliance (r = 0.91) than for the amount of ventilation (r = 0.67) or the inflation pressure alone (r = 0.46) versus the measured static compliance of the respiratory system. PMID- 2192498 TI - [Food allergies and pseudo-allergies--mechanism, clinical aspects and diagnosis]. AB - Allergic and pseudoallergic reactions caused by foods respectively food-additives present cutaneous (urticaria, erythrodermia), gastrointestinal (nausea, vomiting, diarrhoea) and respiratory symptoms (allergic bronchial asthma). The anaphylactic shock is the most severe manifestation. Exact diagnosis is based on anamnesis, skin-tests, laboratory investigations, dietetic test procedures and oral provocation. In allergic and pseudoallergic reactions the adequate therapy is the avoidance of the causative agent (diet). PMID- 2192500 TI - [Special problems of nutritional therapy in chronic kidney insufficiency in the pre-dialysis stage]. AB - The main objectives of medical and nutritional management of patients with chronic renal failure are to slow down the progression of renal disease and to prevent secondary complications due to hypertension, uremic metabolic disturbances, and bone disease. The importance of nutritional measures for this purpose is increasingly recognized. In the setting of vitamin D and calcium deficiency secondary hyperparathyroidism and retention of phosphate result in renal osteodystrophy. An increase in dietary calcium and avoidance of foods rich in phosphate are important. In some patients supplementation of vitamin D3 may be necessary while calcium homeostasis is monitored during follow up. The dietary protein content can influence the severity of the uremic state. Normal or increased consumption of protein may accelerate the progression of renal disease due to the accumulation of nitrogenous products. In addition, uremia itself may cause loss of appetite and thus accumulation of endogenous nitrogen compounds as a result of protein catabolism. Protein restriction under such circumstances may cause malnutrition and an associated increase in morbidity and mortality. Thus, dietary management must consist of individually designed restriction of total protein intake with ingestion of high value protein. This allows balanced nitrogen metabolism with a reduction in circulating uremic toxins. PMID- 2192499 TI - [Prevention and therapy of obesity with diet and sports, an ambulatory therapy program for overweight children]. AB - Dietary restriction together with ongoing power-orientated training provide best results in the therapy and prevention of obesity. Diet can reduce the resting metabolic rate by up to 20% within 14 days. Physical activity stimulates the resting metabolic rate and counteracts this energy saving effect, but is especially important for maintaining a steady state after weight reduction. Exercise reduces the risk factors accompanying obesity by favorable adaptation of the sympathoadrenergic system to physical activity. This can be seen in the effects on heart rate, stroke volume, blood pressure, as well as glycogenolytic and lipolytic activities. Body fat especially in the abdominal area, which is particularly connected with atherogenic risk, is diminished. Weight reduction is accompanied by a decrease of the cardioprotective cholesterol fraction. Diets high in unsaturated fatty acids combined with a staying power training have a synergistic effect: they reduce a decrease of HDL. It is difficult to demonstrate risk factors connected with overweight children. However, from the preventive medicine point of view it is advisable to start with therapeutic measures during childhood. In an out-patient pilot project we surveyed 18 obese children aged 9 to 13 years. The therapy plan consisted of dietary restriction (1200 kcal/d), an exercise program performed 3 times a week, and psychological assistance. All children of 12 to 13 years arrived at an overweight level less than 20%, the younger ones displayed a lower weight reduction effect. All 18 improved their aerobic capacity. In the 1st months of treatment, HDL-cholesterol decreased slightly, but increased above pre-treatment level, later on. We did not see any vitamin deficiencies during the therapeutic regimen. PMID- 2192501 TI - Research on smoking and lung cancer: a landmark in the history of chronic disease epidemiology. AB - This paper describes the history of the epidemiologic research on lung cancer prior to 1970 and its effect on chronic disease epidemiology. In the 1930s, epidemiology was largely concerned with acute infectious diseases. As the evidence grew that the incidence of lung cancer was increasing among men, however, epidemiologists undertook research into the etiology of the disease. In 1950, Doll and Hill, in England, and Wynder and Graham, in the United States, published substantial case-control studies that implicated the use of tobacco as a major risk factor for the disease. A controversy developed over the credibility of this finding and was increased in 1954 when a cohort study by Doll and Hill and another by Hammond and Horn each gave estimates that the risk of lung cancer was greatly increased among smokers relative to the risk among comparable non smokers. An account is given of the disputes surrounding these and related studies. The controversy had a stimulating effect in fostering the developing discipline of chronic disease and epidemiology. PMID- 2192502 TI - [Health behavior and cardiovascular risk factors in females in relation to their marital status]. AB - This is an overview of the literature analysing the international level of knowledge about the influence of marital status on the prevalence of cigarette smoking, hypertension, hyperlipoproteinemia, obesity, alcohol consumption and type-A-behavior of women. An accumulation of the more behavior-dependent risk factors cigarette smoking and alcohol consumption was found by divorced and of the obesity by never married women. Widowed women scarcely differ from women in other marital status groups in their risk factor profile. The risk factors hypertension and hyperlipoproteinemia hardly correlate with the marital status. The overcome-behavior by loading is discussed as one possible cause of the found correlations. That's why family and social support has got a preventive consequence. PMID- 2192504 TI - Dose-finding of cisapride in non-ulcer dyspepsia. PMID- 2192503 TI - [Antro-duodenal coordination: definition, effect of prokinetics and possible relationship to non-ulcer dyspepsia]. PMID- 2192505 TI - [Cisapride for the treatment of irritable stomach--results of 2 multicenter studies]. PMID- 2192507 TI - [Pathophysiology of gastric motility]. PMID- 2192506 TI - [Treatment of diabetic gastroparesis]. PMID- 2192508 TI - [Cisapride versus ranitidine in reflux esophagitis]. PMID- 2192509 TI - Cisapride in the treatment of chronic intestinal pseudo-obstruction. PMID- 2192510 TI - [Gastroprokinetics in the treatment of stomach ulcer: a direct comparative study of cisapride versus ranitidine]. PMID- 2192511 TI - [Which forms of constipation could benefit from motility-active drugs?]. PMID- 2192512 TI - [Nuclear magnetic resonance angiography: principles and uses]. AB - Nuclear magnetic resonance (NMR) angiography is a novel concept in vascular imaging. The method is noninvasive and contrast agents are not required. As in radiographic arteriography, the morphology of the intima is defined indirectly by visualizing the vessel lumen. Similar to vascular ultrasound, the blood flow and the arterial wall dynamics can be studied. NMR angiography is based on a modulation of the amplitude or the phase of the resonance signal due to the motion of the blood in conjunction with a modified two- or three-dimensional (2D; 3D) imaging pulse sequence. Based on the currently available evidence, neurovascular pathology is optimally visualized using the nontriggered 3D inflow angiography. The peripheral vascular pathology was successfully imaged using the sequential 2D inflow approach. Suboptimal definition of vascular lesions currently represents the most important limitation of the available angiographic technology. Due to the limited clinical experience it would be premature to predict the future role of NMR angiography in vascular medicine. The efforts to further develop and clinically test this highly promising technology are, however, fully justified. PMID- 2192513 TI - [Reform of the guardianship and health care right--a contribution of government to the protection of the elderly]. AB - People over the age of majority who are in need of help because of age or sickness must be protected by a modern law of guardianship. Current law with its provisions for declarations of incapacity, guardians for non-minors and tutelage for the frail or infirm rests on outdated concepts of the nineteenth century. Science and practice agree that there is an urgent need for reform. It is not possible to be content with the constitutionally guaranteed principle of proportionality (the requirement that laws bear a reasonable relationship to the ends they are intended to effect); current law permits limitations on legal capacity but does not fully protect either the ward or the involved legal transactions. Current law also does not sufficiently assure that the ward receives personal attention from the guardian or tutor. The German Federal Government has now proposed a draft Guardianship Law. This draft is designed to limit intrusions into the rights of affected persons while also procedurally improving their legal position. The authors approve of this goal; they discuss the essential provisions of the proposed law and come to critical judgments about them. PMID- 2192514 TI - [Knowledge of accident causation research in relation to age-induced decrease in the performance of elderly motorists, their accident risk and legal consequences]. AB - Elderly motorists lose a significant amount of their mental(-somatic) and sensomotor capabilities. No data is available on the percentage of elderly motorists involved in car accidents. Their accident risk, however, is not above average because that decrease is outweighed by increased experience and a more thoughtful manner of driving. The percentage of elderly, especially female pedestrians killed by autos is very high. This is mainly due to age-specific mortality and to the high proportion of aged people, especially women, within the population. Our jurisdiction concerning responsibilities requires elderly people to become aware of any deficiencies and to take them into account. The administrative courts are very reserved in withdrawing driving licenses because of age-caused deficiencies. The mere fact that a driver is very old does not suffice; it even does not justify seeking a psychomedical opinion. In this paper it is argued that actions provided for by the law and regulations asking for a periodical check-up of sensomotor and mental capabilities of the elderly driver are disproportionate. Introducing an "eye-certificate" for all motorists as suggested by the German Ophthalmological Society, however, is considered useful and appropriate since deficiencies of vision have been discovered for all age groups. PMID- 2192515 TI - [Effect of suppressive and activating glycoconjugates on lymphocytes]. PMID- 2192516 TI - [Clinical use of colony-stimulating factors]. PMID- 2192517 TI - [Effect of various physical factors on clinical and laboratory indicators and on nonspecific resistance of the body in reactive arthritis]. AB - Application of UV-therapy and acupuncture in the complex therapy and rehabilitation of reactive arthritis patients had a positive effect on the disease course. The clinical efficacy of the compared physiotherapy methodologies is determined, to a certain degree, by the increase in the nonspecific resistance of the organism in this category of patients. PMID- 2192519 TI - [Individual age determination using growth rings in the cementum of buried human teeth]. AB - Incremental lines of the dental cementum were used for individual age determination in 102 teeth. 66 of them come from different historic periods, 15 teeth were cremated. 36 modern teeth of known age were use as controls. The incremental lines were investigated by use of 100 microns thin cross-sections of the root. Age determination by this method was possible in every tooth, independent of incinaration of various burial conditions. The individual age was determined by adding the mean value of the repeatedly counted incremental lines to the sex-specific eruption age of the tooth in question. Since average deviation from known age is +/- 3.23 years only, counting the incremental lines represent a very advantageous, quantitative method for individual age determination. PMID- 2192518 TI - Rapid and sensitive identification of human blood by an ELISA-ABC method using a biotinylated antibody against human HbA0. AB - A direct enzyme-linked immunosorbent assay (ELISA) using an avidin-biotin complex (ABC) system for the identification of human blood is described. In this ELISA ABC method, in which biotin-labeled goat IgG antibody against human HbA0 was used, it was possible clearly to distinguish human blood from the blood of other species, including that of Japanese monkeys. It took about 3 h to obtain the results. Human Hb concentrations ranging from 22 ng to 169 micrograms produced a positive reaction, and the minimum detection limit in terms of the highest possible dilution of human blood was 1:640,000. PMID- 2192520 TI - [Carotid and vertebral artery circulation in forearm choke holds in Doppler sonography]. AB - By means of continuous wave doppler the effect of two choke holds (Carotid sleeper, Nami-juji-jime) on the carotid and vertebral arteries was investigated. For both choke holds, which are characterized by pressure on lateral parts of the neck, we found an obstruction up to a complete stop of flow. The degree of obstruction depended on the direction of force. The vertebral artery can be compressed between the subclavian artery and the foramina transversaria, therefore it was most effective to press on the lower neck. Tensing the neck muscles can reduce the effect of choking. PMID- 2192521 TI - [Current diagnosis of impotence]. AB - In recent years the true incidence of impotence due to organic diseases in comparison with psychogenic disorders could be verified. New diagnostic tools as penile Doppler ultrasonography, PBI estimation, NPT measurement, invasive SKIT's, neurophysiological methods, selective phalloarteriography, artificial erection and dynamic cavernosography are introduced and are the guide to therapeutic approach. PMID- 2192522 TI - [Fertility assessment based on sperm examination]. AB - Male fertility is indirectly evaluated by analysis of semen. Two questions must be answered in connection with an investigation program. 1. Which prerequisites must the spermatozoa fulfill to the fertilization of oocytes in vivo and to the induction of a normal embryogenesis? 2. Which laboratory tests can be taken as an in vitro model for the fertilization process? Fertilization consists of various steps which require different spermatozoal functions. Several methods were developed to test in vitro whether the semen sample is capable to realize the sequence of fertilization, whereas, it is supposed that there is a close connection between the laboratory test in vitro and the fertilization in vivo. The methods of sperm analysis are presented and their medical practice and predictive value is discussed. PMID- 2192523 TI - [Fournier gangrene]. AB - It is reported on symptoms, diagnostics and treatment of Fourniers gangrene. The early diagnosis is important for effective and successful treatment of this rare condition. PMID- 2192524 TI - [Pathology of the placenta. I. Preliminary anatomic remarks, microscopic findings and sampling of material]. AB - The first part of this review of pathological aspects relating to the placenta is made up of introductory comments on the material that is subject of histological investigation as well as on clinical questions and a thorough description of macroscopic findings. Hints are also given on collection of placental samples and histological investigation. The coverage is completed by a few comments on the normal anatomy of the placenta. PMID- 2192525 TI - Cleaved and multilobated cell immunocytoma of low grade malignancy with amyloid. An immunohistochemical and electron microscopical study. AB - An unusual variant of immunocytoma of low grade malignancy, cytologically resembling follicular cleaved-cell malignant lymphoma is described. Presence of heavy deposits of amyloid, intracytoplasmic monoclonal IgM-kappa immunoglobulin, cells with Dutcher inclusions, electron-microscopic features and negativity of T cell markers led to diagnosis of immunocytoma. After cytostatic chemotherapy the lymphoma changed its morphology into typical lymphoplasmacytoid immunocytoma. PMID- 2192526 TI - [The history of the Pathologic Museum of the Berlin Charite Hospital. 4. The remarkable events concerning a twin monster from Eupen]. AB - A legal dispute broke out in Eupen near Aachen, 1873, and was to be protracted through 14 years. The case was about a twin monster that had died at or after birth. A physician in Eupen, at the same time public servant in the local government, was aware of Virchow's interest in collecting cases. He obtained the two interconnected dead bodies from the parents and promised the latter a sizeable amount of money, obviously assuming that Virchow had at his disposal funds for compensation, as had been the case with Rudolphi and Muller, some time before. The twin monster was sent to Berlin, but no money showed up. The parents sought legal counsel with their local police commissioner who also held the post of local attorney. The attorney opened an investigation, and the district commissioner got involved. The physician was officially reproved by the Aachen government for having trespassed his authority in obtaining the twin monster. Two questions were now cropping up in Eupen: Did Virchow pay money to the local physician? If so, why did the latter fail to pass it on to the parents? This might be a case for civil action. The police commissioner promised the parents to see Virchow in Berlin and to ask him for clarification. The father, when interrogated, insisted that one of the children had definitely lived for a short time after birth. This would entail a penal case on the physician and a charge of law-breaking. But this could be averted. The police commissioner managed to go to Berlin not before 1887. Hoping to have a legal claim to embezzled money even after 14 years, he intended to call on Virchow for questioning. Yet, he missed him and left behind a letter with a request for information on those past developments. PMID- 2192527 TI - [Problems of the agreement of clinical and postmortem diagnoses. Comment on the article by F. Vollmar (Zentralbl. allg. Pathol. pathol. Anat. 1989; 135:699 704)]. PMID- 2192528 TI - Acta Ophthalmologica supplements. PMID- 2192529 TI - The response of the light reflex of retinal vessels to reduced blood pressure in hypertensive patients. AB - The response of retinal arteries and veins to 3 months of antihypertensive medication was studied in 10 patients (39-56 years old) with essential hypertension. We used computerized microdensitometry on fundus photographs, a technique allowing for objective and simultaneous measures of the caliber of blood columns and the width and intensity of their central 'light reflex'. A moderate lowering of diastolic and systolic blood pressures (P less than 0.001) resulted in a significant reduction in the intensity of reflection from retinal arteries (38.6%; P less than 0.005). An increase in the width of the blood column (2.8%; n.s.) and the reflex (8.6%; n.s.) was indicated. Traditionally, changes in light reflectivity has been associated with arteriosclerosis of the vessel wall. The study shows, however, that the vascular reflex is most sensitive to changes in the systemic blood pressure. This signals a need for critical reviewal of interpretation and usefulness of classical grading systems of ophthalmoscopic signs of hypertensive retinopathy. PMID- 2192530 TI - Serum beta-2 microglobulin level in sympathetic ophthalmitis. AB - Serum beta-2 microglobulin (beta 2-m) levels were measured in 12 patients with sympathetic ophthalmitis, 34 with neglected traumatic uveitis following penetrating injury and 36 healthy subjects by ELISA technique. There was no significant alteration of its level in patients with traumatic uveitis. However, its levels were significantly increased in patients with sympathetic ophthalmitis. They were high even in the early stage of the disease. Serum beta 2 m levels paralleled the severity of disease. It decreased significantly at the remission stage. Four patients came back with relapse of the condition and the level of serum beta 2-m was again found to be elevated in them. It is proposed that estimation of beta 2-m can be used as a diagnostic aid when the diagnosis of sympathetic ophthalmitis remains doubtful on clinical grounds. It is also suggested that a rise in serum beta 2-m in patients with traumatic uveitis following perforating injuries may point to the onset of sympathetic ophthalmitis. The extent of rise in its level may be considered a good parameter of the degree of severity of sympathetic ophthalmitis. It may also act as a useful tool to evaluate the drug efficacy in this disease and predict relapse. PMID- 2192531 TI - Signal processing for the profoundly deaf. AB - Profound deafness, defined here as a hearing loss in excess of 90 dB, is characterized by high thresholds, reduced hearing range in the intensity and frequency domains, and poor resolution in the frequency and time domains. The high thresholds call for hearing aids with unusually high gains or remote microphones that can be placed close to the signal source. The former option creates acoustic feedback problems for which digital signal processing may yet offer solutions. The latter option calls for carrier wave technology that is already available. The reduced frequency and intensity ranges would appear to call for frequency and/or amplitude compression. It might also be argued, however, that any attempts to compress the acoustic signal into the limited hearing range of the profoundly deaf will be counterproductive because of poor frequency and time resolution, especially when the signal is present in noise. In experiments with a 2-channel compression system, only 1 of 9 subjects showed an improvement of perception with the introduction of fast-release (20 ms) compression. The other 8 experienced no benefit or a slight deterioration of performance. These results support the concept of providing the profoundly deaf with simpler, rather than more complex, patterns, perhaps through the use of feature extraction hearing aids. Data from users of cochlear implants already employing feature extraction techniques also support this concept. PMID- 2192532 TI - How much do we gain by gain control in hearing aids? AB - This paper considers three rationales for the use of automatic gain control (AGC) in hearing aids, and particularly multi-channel AGC. One rationale is to restore loudness relations among the acoustical elements of speech to what they would be for a normal ear. At present, there seems to be little evidence to support the idea that such loudness relations are critical for speech intelligibility. A second rationale is to reduce the effects of narrowband interfering sounds. This may be applicable in some restricted situations, but not in many others. The third rationale, the one considered here to be most important, is to ensure that all of the important elements in speech are comfortably audible. This can be achieved using two forms of AGC: slow-acting AGC operating on the whole speech signal, to compensate for variations in overall sound level from one situation to another; and fast-acting (syllabic) compression acting independently in a number of bands, to compensate for differences in level of acoustical elements within speech. To reduce spectral and temporal distortions introduced by the syllabic compression, the number of bands should be small (probably two or three) and the amount of compression should be the minimum required to ensure that all of the important elements in speech are audible. It is concluded that gain control can be useful for increasing user comfort and for ensuring the audibility of speech sounds. It is not likely to restore impaired hearing to normal for most patients, but may usefully be employed in conjunction with other forms of signal processing. PMID- 2192533 TI - Prospects for speech pattern element aids. AB - A brief discussion is given of new hearing aids which are based on the use of speech pattern elements. Their operation essentially involves the reduction of the complex acoustic structure of the original speech signal into simpler sets of perceptually clear components which are then encoded for maximally relevant presentation to the listener. This approach has four primary features which may contribute crucially to future advances. First, by providing for external analysis, reduced or even non-existent ability in the impaired ear can be palliated. Second, by the selection of appropriate elements of the original speech signal, the stimulation can be tailored so that it matches the residual auditory ability--psychophysical and cognitive--of the deaf person. Third, the speech, language, and also environmental needs of the individual adult or developing child can be met in structured ways. Fourth, the use of selective pattern sensitive analysis methods makes it possible in practice to provide a degree of in-built immunity to domestic and working acoustic environments. PMID- 2192534 TI - Studies with digital hearing aids. AB - Digital hearing aids offer many advantages over conventional hearing aids. These include signal-processing capabilities that are superior to those of a conventional analog hearing aid, methods of signal-processing and control that are unique to digital systems and which cannot be implemented in conventional analog hearing aids, and innovative new techniques that are changing our way of thinking about hearing aids. An example of the first of these advantages is the extremely high precision with which the frequency-gain characteristic can be specified and the use of this capability to study the effects of frequency response irregularities commonly encountered with hearing aids. An example of the second advantage is the use of memory and logical operations in the implementation of multivariate adaptive paired-comparison techniques for more effective hearing-aid prescription. Another example is the use of powerful new signal processing techniques for noise reduction. The third advantage is the most important. The digital hearing aid can be viewed as a generalized hearing instrument which can be used for simulation, testing and prescription, as well as amplification. The use of the digital hearing aid as a simulator of other hearing aids is discussed and an illustrative example provided in which a new form of amplitude compression, orthogonal-polynomial compression, has been simulated using a digital master hearing aid. PMID- 2192535 TI - Noninvasive methods to study autonomic nervous control of circulation. AB - The major findings and conclusions of this study are the following: 1. Indirect evidence suggested that nervous afferentation from the cutaneous thermoreceptors and nervous efferentation to the skin blood vessels mediated the 0.01-0.10 Hz thermally entrained response of the oscillations of the forearm skin blood flow in supine and upright subjects. 2. Postural stimulation decreased skin blood flow and oscillations of skin blood flow. The 0.10 Hz thermal stimulation interacted with the postural stimulation by increasing the oscillations of skin blood flow from sitting to standing position on the contrary to the expected postural effect. 3. The thermal entrainment of periodic heart rate variability was not constant. Both 0.01-0.10 Hz thermal and postural and sensory stimulations affected the periodic heart rate variability selectively at the frequency of the periodic stimulus or the less than 0.12 Hz frequencies. 4. The periodic thermal stimulation had a frequency-selective effect on the oscillations of the neonatal heart rate. The thermally stimulated reactivity increased with an increased maturity of a neonate. 5. Intermittent tilting had a frequency-selective influence on the oscillations of heart rate. Continuous deep breathing entrained the periodic heart rate variability. The estimation of the power spectral density function of heart rate quantified the chronotropic respiratory effects more accurately than the statistical indices of heart rate variability. 6. Response of periodic heart rate variability to intermittent tilting and deep breathing stimulation suggested normal vagal control of heart rate in children with juvenile diabetes and juvenile rheumatoid arthritis. 7. Normal vagal bradycardic response was found during the phase IV of the Valsalva manoeuvre in functionally abnormal nervous control of circulation. The simulated diving test was not found clinically useful. 8. The ratio of electrical to electromechanical systole of the heart was greater than 1.00 both at rest and during the orthostatic, Valsalva and diving reflex tests. This finding suggested constantly exaggerated sympathetic cardiac inotropic control during vagal and sympathetic stimulation of heart rate. 9. The decreased thermally stimulated heart rate variability was interpreted as an indication of inhibited vagal modulation of the sinoatrial node of the heart in subjects with dystonic symptoms and orthostatic intolerance. The exaggerated sympathetic reactivity of these subjects explained the abnormally high gain of periodic heart rate variability to 0.01-0.03 Hz periodic thermal stimulation. PMID- 2192536 TI - Analysis of endothelin-1-induced contractions of guinea-pig trachea, pulmonary veins and different types of pulmonary arteries. AB - Endothelin-I (ET-I), a peptide produced by the vascular endothelium, has been found to produce strong and persistent contractions of various blood vessels. In the present study, the effects of ET-I were studied on isolated pulmonary arteries from four different levels (main pulmonary artery, large lobar arteries, small lobar arteries and intrasegmental arteries) of the guinea-pig. In addition, the effects of ET-I on pulmonary arteries were compared with those of pulmonary veins and trachea. ET-I elicited a strong concentration-dependent contraction of pulmonary arteries, veins and trachea. The effects of ET-I were more pronounced in pulmonary arteries than in corresponding veins. Significant regional variations within the pulmonary arterial system were disclosed. The tracheal segments showed the same sensitivity and the same degree of relative maximal contraction as the pulmonary veins. Although the cellular mechanisms behind the action of ET still are not clear, our results favour a direct action of ET-I on the vascular smooth muscle during vasoconstriction. Furthermore, the ET-I-induced contraction in guinea-pig lung seems to be independent of extracellular calcium. PMID- 2192537 TI - Actions of endothelin on isolated corpus cavernosum from rabbit and man. AB - The effects of endothelin, a vasoconstrictor peptide produced by vascular endothelial cells, were investigated in isolated rabbit and human corpus cavernosum (CC). Preparations from both rabbit and man were potently contracted by endothelin in a concentration-dependent manner. The contractions developed slowly, could not be reversed despite frequent washings, and were only partly inhibited by the Ca2+ channel blocker nimodipine. Even in Ca2(+)-free medium containing the chelator EGTA a small contractile component persisted. In rabbit CC, the contractions in Ca2(+)-free medium were not affected by nimodipine, the Ca2(-)-channel agonist BAY K 86(44), or by depletion of intracellular Ca2(+) stores sensitive to noradrenaline (NA) and caffeine, but were almost abolished by the protein kinase C inhibitor H7. In both rabbit and man, carbachol and vasoactive intestinal polypeptide concentration-dependently relaxed preparations contracted by endothelin. The relaxations induced by carbachol were antagonized by atropine. Endothelin enhanced concentration-dependently the contractions induced by exogenously applied NA in rabbit CC. The enhancement was more pronounced at low concentrations of NA. This study shows that endothelin potently contracts isolated penile erectile tissue. The contraction seems to be mediated mainly by influx of Ca2+ through the cell membrane, which partly occurs through a pathway other than voltage-operated calcium channels. However, involvement of other mechanisms cannot be excluded. The results suggest that endothelin can play a role in penile erectile mechanisms. PMID- 2192538 TI - Influence of verapamil on regional renal blood flow: a study using multichannel laser-Doppler flowmetry. AB - In anaesthetized male Sprague-Dawley rats the influence of the calcium entry blocker verapamil (2.4 mg h-1 kg-1, i.v.) on renal superficial cortical (CO) and outer medullary (OM) blood flow was investigated with the aim of elucidating further the intrarenal heterogeneity in vasoreactivity. The blood flow of the two regions was monitored simultaneously with a laser-Doppler flowmeter, using fibre probes with an outer diameter of 0.75 mm. One probe was directed towards the cortex and a second probe was inserted through the cortex and positioned in the outer medulla, measuring the flow within a hemisphere with a depth of 0.5-1.0 mm. The OM probe position was verified by dissecting the kidneys after each experiment. Insertion of the OM probe did not affect whole-kidney glomerular filtration rate, renal plasma flow or electrolyte excretion. Thirty minutes of verapamil infusion increased OM blood flow by 26%, but did not change CO blood flow (-1%). In spite of the increase in OM blood flow, the urine osmolality remained unaltered. Sodium excretion increased by 39%, while potassium excretion was unchanged. Mean arterial blood pressure decreased by 13%. In conclusion, this study has further supported the suggestion that the vasoreactivity is higher in the juxtamedullary than in the superficial cortical vasculature. The heterogeneity of the response is most probably due to the previously documented pressure drop along the interlobular arteries, which will create different haemodynamic conditions for the juxtamedullary and superficial afferent arterioles. PMID- 2192539 TI - Albumin protects against capsaicin- and adenosine-induced bronchoconstriction and reduces overflow of calcitonin gene-related peptide from guinea-pig lung. AB - In the guinea-pig isolated, perfused lung, the effect of albumin on oedema formation and bronchoconstriction as well as on capsaicin-induced overflow of calcitonin gene-related peptide-like (CGRP-LI) immunoreactivity has been examined. CGRP was used as an indicator of sensory nerve activation since it is more stable than the tachykinins substance P and neurokinin A. As expected, the lung water content was significantly (P less than 0.001) higher in lungs perfused with albumin-free buffer than when the buffer contained 4.5% albumin. Also, in albumin-free buffer the baseline airway resistance (RL) was increased and dynamic compliance (CDYN) reduced (P less than 0.001). Capsaicin (1 x 10(-6) M) was about 100 times less potent as a bronchoconstrictor when preincubated with albumin for 45 min, and the associated overflow of CGRP-LI was inhibited (from 221.0 +/- 63.4 fmol to 8 fmol fraction-1). When CGRP (50-200 pM) was incubated for 60 min with albumin, the recovery of CGRP-LI was 48% lower (P less than 0.01) than in the absence of albumin, corresponding to a loss rate of about 1% min-1. Catabolism or binding of neuropeptides can therefore hardly explain the diminished bronchoconstrictor potency of capsaicin. Capsaicin was also less effective as a constrictor in isolated bronchi after preincubation with albumin, suggesting that capsaicin itself may be bound or absorbed to this macromolecule. The bronchoconstrictor response to adenosine was also diminished in the presence of albumin. Adenosine was about 1000 times less potent as a bronchoconstrictor if dissolved in albumin 45 min before infusion, but only 10 times less potent when administered as bolus doses to albumin buffer-perfused lungs. Metabolism of adenosine may be the reason for the decreased potency of adenosine. The enzymatic activity may have been associated with impurities in the albumin preparation used (bovine serum albumin fraction V is greater than or equal to 96% pure) or contained in the protein itself. Since the bronchoconstrictor effect of acetylcholine was not reduced in the presence of albumin, it is not likely that albumin affects directly the contractility of the smooth muscle. These data demonstrate the importance of studying the influence of albumin on the in-vitro actions of pharmacological agents. The absence or presence of albumin products in nutrient buffer solutions may mean dramatic differences in potencies of certain drugs. Furthermore, bolus injections of agents are preferable, and preincubation together with albumin should be avoided. PMID- 2192540 TI - Nature of the genetic contribution to psychotic illness--a continuum viewpoint. AB - The recurrent psychoses, rather than, as Kraepelin supposed, constituting 2 major entities, manic depressive illness and schizophrenia, as separate diseases, may be distributed along a continuum that extends from unipolar depressive illness through bipolar and schizoaffective psychosis to schizophrenia with increasing severities of defect state. It is proposed that this continuum rests on a genetic base, variations in the form of the gene accounting for variations in form of psychosis. The simplest interpretation of the continuum is that such variation relates to changes at a single genetic locus. Evidence from a postmortem study of brain structure in schizophrenia suggests that this is the gene that determines the development of asymmetries in the human brain, i.e., the cerebral dominance gene or right shift factor of Annett; a possible genomic location is in the pseudoautosomal region of the sex chromosomes. PMID- 2192541 TI - [Age at menarche and age at marriage in earlier centuries]. AB - Data from parish registers have been used to estimate the menarcheal age during the 17th and 18th centuries in a village population which lies in a part of the northern lower reaches of the Harz mountains. The results, obtained by using a formula developed by the author, agree with information obtained from authors of the 17th and 18th centuries. Data from the literature on the age of menarche and marriage from the classical period up to the present time are being reviewed and evaluated. The basic observation is that the longterm fluctuations of menarcheal age run concurrently with changes in the food resources available during the respective time spans. PMID- 2192542 TI - Maternal psychological stress/depression and low birth weight. Is there a relationship? PMID- 2192543 TI - Radiological case of the month. Mesenteric cyst with hemorrhage. PMID- 2192544 TI - Condylomata acuminata in the pediatric population. AB - The incidence of condylomata acuminata infection has shown a steady increase for adults and children in recent years. With the discovery that the viral agents of this disease are potentially neoplastic, a disorder that was once considered a nuisance is now taking on new-found importance and concern. Furthermore, the knowledge that these lesions are often sexually transmitted and the ever increasing concern over child abuse have combined to make the recognition and treatment of this disease in the pediatric population of even greater significance. Depending on location, podophyllum resin (podophyllin) is the initial therapy of choice. Available studies indicate a cure rate ranging from 22% to 98% depending on location of the warts, frequency of treatment, patient compliance, and freshness of the podophyllum resin preparation. Cure rates of 91% to 97% have been reported with cryotherapy and laser photocoagulation. Eradication of the viral agent and long-term follow-up are important. PMID- 2192545 TI - The validity of self-reported exercise-induced sweating as a measure of physical activity. AB - The validity of self-reported hours in which one engages in activities strenuous enough to produce sweating was assessed as a measure of physical activity. Respondents were 732 randomly selected adults between the ages of 25 and 65 years from the Boston, Massachusetts, metropolitan area who participated in a field trial of health risk appraisal instruments in 1987. A total of 68% of the men and 57% of the women in the sample were involved in sweat-inducing activities at least once per week. The correlation between the natural logarithm of reported sweat hours per week and energy expenditure measured by the Harvard Alumni Activity Survey was 0.39. Following a logarithmic transformation and adjustment for age and sex, sweat hours was significantly correlated with high density lipoprotein cholesterol (r = 0.11, p less than 0.05). However, these associations were not as strong as those found for the age- and sex-adjusted log of the Harvard Alumni Activity Survey score (r = 0.19 and r = -0.15 for high density lipoprotein cholesterol and body mass index (weight (kg)/height(m)2), respectively) and are considerably weaker than those reported in other studies using sweat episodes (days per week on which sweating occurred) as an indicator of physical activity. These results suggest that the utility of self-reported sweat hours may be limited to distinguishing active from inactive subjects in epidemiologic surveys. PMID- 2192546 TI - Prediction of osteoporotic fractures in the general population by a fracture risk score. A 9-year follow-up among middle-aged women. AB - The possibility of predicting the occurrence of fractures on the basis of risk factors for osteoporosis was evaluated between 1975 and 1986 in a follow-up study of 1,014 women aged 45-64 years from a Dutch population sample. During the 9-year period of follow-up, 16% of the women experienced one or more fractures. Of 12 historical and radiologic risk factors for osteoporosis which are considered important in the biomedical literature, none were found to be strong indicators of future fractures. Complete information on risk factors was available for 742 women. A fracture risk score was calculated for each person by combining the simultaneous influence of several risk factors in a multivariate analysis. The risk score discriminated relatively well between women with high and low risks of fractures. The risk ratio between the highest and the lowest risk score quintiles was 6.4 for all fractures and 7.0 for type I osteoporotic fractures (fractures of the vertebral bodies and distal forearm). However, if belonging to the highest quintile was considered as a screening test for fracture prediction, the sensitivity and specificity were poor: 0.37 and 0.84, respectively, for all fractures and 0.48 and 0.83, respectively, for type I osteoporotic fractures. These results indicate that it might not be efficient to use risk factor status to select women for fracture prevention programs. PMID- 2192547 TI - A prospective study of persistent diarrhea among children in an urban Brazilian slum. Patterns of occurrence and etiologic agents. AB - Persistent diarrhea is a major health problem among children in developing areas of the world. Since few community-based studies have addressed the epidemiology or etiology of this condition, we undertook prospective diarrheal surveillance among a cohort of 175 children less than 5 years of age over a 28-month period in an urban slum in northeastern Brazil. Very high diarrhea illness burdens were found. The children in this cohort had an average of 11 episodes per year and spent 82 days per year with diarrhea. A total of 65% of children had at least one episode of persistent diarrhea (greater than or equal to 14 days duration). These episodes accounted for 50% of all days of diarrhea and 11% of all episodes. The occurrence of at least one episode of persistent diarrhea identified all children who spent at least 15% percent of days with diarrhea. Among children with and without diarrhea, rotavirus was the agent isolated most frequently, followed by Giardia lamblia and enterotoxigenic coliforms. The agents isolated from children with acute and persistent diarrhea were similar, which suggests that other factors must be operative in the development of persistent diarrhea. PMID- 2192548 TI - Epidemiologic implications of limited-duration seropositivity after toxoplasma infection. AB - In the Netherlands, the prevalence of immunoglobulin G antibodies against Toxoplasma shows a plateau at older ages. The titer distributions in the indirect fluorescent antibody (IFA) test do not change after the age of 40 years. In recent serologic studies, it has been observed that enzyme-linked immunosorbent assay of toxoplasma antibodies yields much higher seroprevalence values at older ages. These findings indicate that IFA seropositivity is not lifelong. It has been suggested in the literature that the IFA data in the older age groups reflect a dynamic balance between reversions to seronegativity and conversions to seropositivity. In this paper, the epidemiologic implications are examined by means of a mathematical model. The seroprevalence data linked to the model indicate that the mean duration of IFA seropositivity after infection is 40 years and that the annual infection risk in the reproductive age group (15-40 years) is 4-6%. A further implication of a limited duration of IFA seropositivity is that a certain fraction of IFA-seronegative persons have experienced an infection in the past. The model-based analysis indicates that the predictive value of a negative IFA test is very low at the older ages. The model is consistent with the available data, and it provides a framework for further theoretical and data related research. PMID- 2192549 TI - The effects of sensitivity and specificity of case selection on validity, sample size, precision, and power in hospital-based case-control studies. AB - The consequences of imperfect sensitivity and specificity in disease diagnosis in epidemiologic studies have conventionally been assessed by models of misclassification which assume a fixed number of study participants. This assumption is not usually applicable to case-control studies in which disease diagnosis is part of the case selection process and sensitivity and specificity will, for a given time period and source of cases, affect the size of the case group. In this paper, a mathematical model that incorporates this is developed in the framework of a hospital-based case-control study. The separate and combined effects of imperfect sensitivity and specificity of case diagnosis on validity, sample size, precision, and power are assessed. The authors conclude that if several diagnostic procedures are available, specificity of case diagnosis should usually take precedence over sensitivity for the sake of validity. Although increasing specificity and sacrificing sensitivity may compromise precision to some extent, the latter can often be fully compensated for by an increased control:case ratio. Imperfect specificity also compromises power despite increased sample size. Since clinical diagnoses tend to focus on high sensitivity and sacrifice some specificity, their uncritical adoption for case recruitment in case-control studies may compromise their validity. PMID- 2192550 TI - Re: "A method for combining matched and unmatched binary data: application to randomized, controlled trials of photocoagulation in the treatment of diabetic retinopathy". PMID- 2192551 TI - Detecting disease clusters: the importance of statistical power. AB - A variety of methods and models have been proposed for the statistical analysis of disease excesses, yet rarely are these methods compared with respect to their ability to detect possible clusters. Evaluation of statistical power is one approach for comparing different methods. In this paper, the authors study the probability that a test will reject the null hypothesis, given that the null hypothesis is indeed false. They present a discussion of some considerations involved in power studies of cluster methods and review two methods for detecting space-time clusters of disease, one based on cell occupancy models and the other based on interevent distance comparisons. The authors compare these approaches with respect to: 1) the sensitivity to detect disease excesses (false negatives); 2) the likelihood of detecting clusters that do not exist (false positives); and 3) the structure of a cluster in a given investigation (the alternative hypothesis). The methods chosen, which are two of the most commonly used, are specific to different hypotheses. They both show low power for the small number of cases which are typical of citizen reports to health departments. PMID- 2192552 TI - Safety and efficacy of loperamide. AB - Loperamide is a safe and effective antidiarrheal for the treatment of acute diarrhea. Efficacy data suggest that loperamide is more effective than the prescription drug diphenoxylate and an over-the-counter bismuth subsalicylate preparation. Loperamide is a safe drug, with few adverse reactions reported worldwide. It also lacks significant abuse potential. Loperamide may prove to be the antidiarrheal agent of choice when compared with currently available nonprescription treatments for acute diarrhea. PMID- 2192553 TI - Comparative efficacy of loperamide hydrochloride and bismuth subsalicylate in the management of acute diarrhea. AB - An open-label, parallel comparison of loperamide hydrochloride (Imodium A-D) and bismuth subsalicylate (Pepto-Bismol) was conducted using nonprescription dosages in adult students with acute diarrhea (three or more unformed stools in the preceding 24 hours plus at least one additional symptom of enteric infection). For the two-day study period, the daily dosage was limited to 8 mg (40 ml) for loperamide-treated subjects and to 4.9 g for bismuth subsalicylate-treated subjects. At these dosages, loperamide significantly reduced the average number of unformed bowel movements relative to bismuth subsalicylate. Following the initial dose of treatment, control of diarrhea was maintained significantly longer with loperamide than with bismuth subsalicylate. Time to last unformed stool was significantly shorter with loperamide than with bismuth subsalicylate. In providing overall subjective relief, subjects rated loperamide significantly better than bismuth subsalicylate at the end of the 24 hours. Both treatments were well tolerated, and none of the minor adverse effects reported resulted in discontinuation of therapy. It was concluded that loperamide is effective at a daily dosage limit of 8 mg (40 ml) for the treatment of acute nonspecific diarrhea and provides faster, more effective relief than bismuth subsalicylate. PMID- 2192554 TI - A randomized, open-label comparison of nonprescription loperamide and attapulgite in the symptomatic treatment of acute diarrhea. AB - The efficacy of nonprescription doses of loperamide hydrochloride (Imodium A-D) was compared with nonfibrous activated attapulgite (Diasorb) in a randomized, parallel, open-label study of adult patients with acute diarrhea. The results of the study showed loperamide to be more effective than attapulgite in the control of diarrhea. Loperamide significantly reduced stool frequency compared with attapulgite, particularly within the first 12-hour period following the start of therapy, and significantly shortened the mean time to last unformed stool (loperamide, 14.2 hours, versus attapulgite, 19.5 hours). Subjective evaluations of severity of enteric symptoms, overall relief following treatment, and overall relief after 48 hours of treatment were equivalent for both drugs. Both treatments were well tolerated, and there was no difference between treatments with respect to the proportion of patients reporting adverse experiences. PMID- 2192555 TI - Acute diarrhea associated with travel. AB - Travelers' diarrhea, an acute illness that affects between 20 and 50 percent of travelers to high-risk areas, is usually acquired by eating contaminated food, drinking contaminated water, or coming in contact with the contaminated hands of an infected person. Travelers' diarrhea can be caused by bacterial, viral, and parasitic agents. The Travelers' Diarrhea Consensus Conference has recommended prophylactic measures, which include proper preparation of food and beverages, nonantimicrobial agents, and antimicrobial agents. The newer quinolone antibiotics and bismuth subsalicylate may also be useful prophylactically. Appropriate treatment methods include oral fluids and electrolyte replacement, nonspecific agents such as bismuth subsalicylate, antimotility agents such as loperamide hydrochloride and diphenoxylate hydrochloride, and antimicrobial and antiparasitic agents. PMID- 2192556 TI - Acute diarrhea in developed countries. A rationale for self-treatment. AB - Acute diarrhea is a common, nonlethal condition that causes frequent inconvenience and economic loss. People rarely consult physicians for this problem. Epidemiologic studies among adults, hospitalized adults, children attending day care centers, homosexual men, and travelers indicate a wide spectrum of etiologic agents. The clinical presentation of acute diarrhea may lead clinicians to consider certain causative agents, but it is not diagnostic of any specific cause. Clinical laboratory studies can detect or isolate pathogens in only a minority of cases. By the time this information is available, patients have usually recovered. For these reasons, early self-treatment aimed at reducing symptoms of acute diarrhea is recommended. PMID- 2192557 TI - Presentation of the Southern Society for Clinical Investigation Founder's Medal to Dr. Jay H. Stein. PMID- 2192558 TI - Acute tubulointerstitial nephritis. AB - Acute tubulointerstitial nephritis (ATIN) is a common disorder characterized by a spectrum of clinical manifestations ranging from asymptomatic urinary abnormalities to acute oliguric renal failure. Tubular dysfunction out of proportion to the degree of renal failure is an important clue to the diagnosis. This review describes its pathogenesis, pathophysiology, diagnosis, differential diagnosis and therapy, emphasizing the drug-induced form of ATIN. PMID- 2192559 TI - Hybridomas using athymic nude mouse injected with Crohn's disease (CD) tissue filtrate. Immunoreactivity of the hybridomas with CD sera. AB - Injections of Crohn's disease (CD) tissue filtrates produce lymphoma and hyperplastic lymph nodes from plasma cell hyperplasia (PCH) in athymic nude (nu/nu) mice; these lymphoid tissue contain an antigen(s) recognized by CD serum/gamma G immunoglobulin (IgG). To immortalize the "CD-reactive antigen(s)," the authors fused the lymphoid cells from a CD tissue filtrate primed nu/nu mouse with nonsecretory mouse myeloma cells. Hybrids were screened and selected based on their reactivity with CD serum IgG, but not with control serum IgG in an indirect immunofluorescence assay (IF). Two CD-positive hybridomas were examined by IF with sera from 47 CD, 38 ulcerative colitis (UC), 13 controls with other gastrointestinal diseases, 19 with autoimmune diseases, and 21 normal subjects. Sera from 16 CD patients (34%) reacted with the two hybridomas, but only one of 38 UC sera and none of the 53 other disease or normal control sera reacted. The immunoreactivity of CD sera was significantly higher than UC sera (P less than 0.01) and each of the other groups (P less than 0.007). Using immunoperoxidase techniques at light and electron microscopic levels, the authors localized CD associated antigen(s) in the plasma membrane of the two hybridomas. Further characterization of these hybridomas and the immunoreactive protein(s) may provide an important probe(s) for the diagnosis and the understanding of the pathogenesis of CD. PMID- 2192560 TI - Hypnotizability and dissociation. AB - The author describes the multidimensionality of hypnosis itself and hence of hypnotizability. He also points to the lack of clarity regarding the concept of dissociation and the extent to which its roots lie in the clinical experience of hypnosis. The concept of dissociation increasingly preempts repression and other defense mechanisms in current nosological thinking. The author cautions against equating hypnotizability scores with dissociative capacity and advocates a clearer elaboration of the concept of dissociation. Meanwhile, restraint in the use of the term "dissociation" is recommended. PMID- 2192561 TI - A review of the depressive personality. AB - A depressive type of personality disorder has been described by both German phenomenologists and psychoanalysts and has been used by clinicians for years. Although this personality type has been included in standard international nosologic systems (ICD-9), it has never been recognized in DSM. This literature review identifies and explores the issues relevant to the possible inclusion of such a category--an axis II personality disorder linked to axis I depressive disorder--in the upcoming DSM-IV. PMID- 2192562 TI - Maintenance treatment and 6-month outcome for bulimic patients who respond to initial treatment. AB - Bulimic subjects who responded to intensive group psychotherapy plus imipramine or placebo or to imipramine alone (N = 68) were assigned to 4-month maintenance with weekly support groups and/or medication (placebo or imipramine) and were evaluated 6 months after initial treatment (N = 61). Thirty percent of the subjects relapsed during the 6 months. Initial treatment with group psychotherapy plus placebo or imipramine was associated with a lower relapse rate than initial treatment with imipramine alone. Neither attendance at the maintenance group sessions nor imipramine maintenance was associated with better outcome. PMID- 2192563 TI - A double-blind, placebo-controlled trial of fluoxetine plus behavior modification in the treatment of obese binge-eaters and non-binge-eaters. AB - To determine whether fluoxetine is effective in the long-term treatment of obesity and whether it is particularly useful in the treatment of obese binge eaters, the authors randomly assigned 45 obese subjects (22 with binge-eating problems and 23 without binge-eating) to fluoxetine (60 mg/day) or placebo in a 52-week double-blind trial. The 21 subjects who completed the trial made 13 clinic visits and were taught basic behavior modification strategies. Patients treated with fluoxetine plus behavior modification lost significantly more weight than those treated with placebo plus behavior modification. However, the drug did not appear to have a differential benefit for binge-eaters. PMID- 2192565 TI - Adequacy of pharmacological treatment. PMID- 2192564 TI - Sertraline in obsessive-compulsive disorder: a double-blind comparison with placebo. AB - Many agents that affect the brain's serotonergic system appear to be at least partially effective in the treatment of patients with obsessive-compulsive disorder. However, in this 10-week double-blind trial in which 10 patients received sertraline and nine received placebo, sertraline was ineffective according to four measures of obsessive-compulsive symptoms. The authors discuss the implications of these preliminary findings for the serotonergic theory of obsessive-compulsive disorder and the need to explore the role of other neurochemical systems in this disorder. PMID- 2192566 TI - The case of the Wolf-Man. PMID- 2192567 TI - Designing fee schedules by formulae, politics, and negotiations. AB - Fee-for-service cannot be used successfully by organized health insurance without a fee schedule. America first tried to pay doctors under Medicare by an involved formula system without a fee schedule, but the effort has failed. The United States has now commissioned a research project to design a unique fee schedule that will precisely reflect physicians' effort and practice costs and that will represent the prices produced by a perfectly competitively market. The primary goal is the same as that pursued recently by reformers in all countries: viz., narrow the spread in fees and income between surgical and cognitive fields. There are serious technical limitations on this effort, despite the talent of the research team. An additional difficulty lies in the nature of the subject: paying the doctor involves conflicts of interest between payers and all doctors as well as among the medical specialties, and the conflicts cannot be resolved by any formulae calculated by any single research team. Methodological and political compromises will be necessary, in order to adopt a reform. The new method may be just as politically driven, complicated, and disputed as the old one, despite America's pretenses that it prefers free markets and opposes excessive government. PMID- 2192568 TI - Atypical pathologic manifestations of Pneumocystis carinii pneumonia in the acquired immune deficiency syndrome. Review of 123 lung biopsies from 76 patients with emphasis on cysts, vascular invasion, vasculitis, and granulomas. AB - The frequency of atypical pathologic manifestations of Pneumocystis carinii pneumonia (PCP) were studied in 123 lung biopsy specimens from 76 National Institutes of Health patients with the acquired immune deficiency syndrome. The following atypical features were observed: interstitial (63%) and intraluminal (36%) fibrosis, absence of alveolar exudate (19%), numerous alveolar macrophages (9%), granulomatous inflammation (5%), hyaline membranes (4%), marked interstitial pneumonitis (3%), parenchymal cavities (2%), interstitial microcalcification (2%), minimal histologic reaction (2%), and vascular invasion with vasculitis (1%). These atypical features are discussed with emphasis on the significance of cavities, vascular invasion, vasculitis, and granulomas. Immunohistochemical staining with monoclonal antibodies to the 2G2 and 6B8 antigens of P carinii in paraffin-embedded lung biopsy specimens did not indicate any diagnostic advantage over routine methenamine silver stains. This study provides an important reminder that a wide variety of pathologic manifestations may occur in PCP in human immunodeficiency virus-infected patients and that atypical features should be sought in lung biopsies from patients at risk for PCP. PMID- 2192569 TI - Multicentric reticulohistiocytosis. Detailed immunophenotyping confirms macrophage origin. AB - A case study of multicentric reticulohistiocytosis is presented with extensive immunohistochemical studies of the infiltrate in both paraffin and cryostat sections. These studies showed that the cells are of monocyte/macrophage origin. B- and T-cell gene rearrangement analysis of multicentric reticulohistiocytosis was also performed and showed a germline configuration. PMID- 2192571 TI - Meningitis after obstetric spinal anaesthesia. AB - A case of meningitis after obstetric spinal anaesthesia is reported. The possible aetiological causes of postspinal meningitis are discussed and the difficulty in differentiation between aseptic and bacterial meningitis noted. Ways to reduce the risk of bacterial contamination of cerebrospinal fluid are mentioned. The patient in this case made a full recovery, but the use of spinal anaesthesia in these patients is open to question. PMID- 2192570 TI - Propofol for long-term sedation in the intensive care unit. A comparison with papaveretum and midazolam. AB - Thirty-seven patients with a wide range of illnesses were studied during mechanical ventilation of the lungs in an intensive care unit. Fifteen were sedated with a continuous propofol infusion, with analgesia provided by bolus doses of papaveretum. Twelve received a continuous infusion of papaveretum, supplemented by bolus doses of midazolam. The level of sedation was assessed every four hours and measurements were made of haemodynamic and respiratory variables. Levels of sedation were generally satisfactory in both groups. Six patients who received propofol required the use of muscle relaxants, because of their strong respiratory drives, to achieve synchronisation with the ventilator. There was no significant difference in respiratory or haemodynamic variables between the groups, but several patients required inotropic support because of their disease. There was no evidence of inhibition of adrenal steroidogenesis in the propofol group. Propofol can be a useful sedative agent in the intensive care unit, but sedative regimens should be tailored to individual patient requirements. PMID- 2192572 TI - [Nalbuphine and piritramid in the postoperative period in young children. 2. External respiration]. AB - The use of opioid analgesics often seems to be necessary for postoperative analgesia in small children. There is a risk however, that interactions between anesthetics and the opioid analgesics may cause significant respiratory depression. There is no reliable information about the influence of nalbuphine and piritramide on respiration in small children. Therefore, the actions of nalbuphine and piritramide versus placebo on the respiratory patterns of 46 children in ASA groups I and II and aged between 1 and 4 years were tested in a randomized double blind trial. METHODS. Selection criteria were: no disturbed development, no signs or symptoms of neurological disease, uncomplicated operation, no pain at time of admission, no indication for urgent operation, written parental consent. Operations, premedication and anesthesia were standardized as mentioned in the comparison paper. Anesthesia was induced and maintained with oxygen in nitrous oxide and halothane (FiO2:0.3). Intubation was performed without the use of any relaxant. Postoperatively the ventilation was continued with the same FiO2 and with 0.5 vol% of halothane over a period of at least 20 min until spontaneous breathing was reestablished and stable ventilatory parameters were obtained. A single bolus injection of either nalbuphine or piritramide 0.1 mg/kg or a placebo was then given i.v.. The breathing parameters VT, VI, respiratory rate, maximal inspiratory flow and the inspiratory/expiratory time ratio were evaluated using the computer-assisted pneumotachometric device with hot wire anemometers (Buttner et al.). They were measured before and 2, 5, 10 and 15 min after the drugs were administered. Capillary blood-gas values were sampled before and 10 min after administration of the drug and again 5 min after extubation. Heart rate and blood pressure were recorded by means of a Dinamap monitor. Statistical analysis of the data was carried out by means of the chi 2 test or Fisher's exact test when appropriate. For the metric data analysis of variance was performed. A full factorial design was calculated with drugs and time after injection as factors and baseline values as a covariate. Multiple comparisons were performed using the Tukey test. The level of significance was set at P less than 0.05. Homogeneity was considered when p greater than 0.2. RESULTS. In spite of randomization the 3 groups could not be regarded as homogeneous for weight. In 4 of the 46 children apnea developed after drug administration and controlled ventilation was needed. These were all in the piritramide group. This result was significant against nalbuphine and placebo. There was no significant correlation between the apnea and any anamnestic, demographic or respiratory parameters. Since apnea and breathing constitute different qualities, a pooling of the apnea data and the non-apnea data within the piritramide group is not allowed... PMID- 2192573 TI - [The effect of continuous arteriovenous hemofiltration on the pharmacokinetics of azlocillin in anuric patients]. AB - The influence of continuous arteriovenous hemofiltration on the pharmacokinetics of azlocillin was examined in eight anuric intensive care patients, each of whom received a short infusion of 5.0 g azlocillin. Azlocillin concentrations in blood were measured simultaneously in the afferent and efferent loops of the amicon Dia 20 hemofilter and in the ultrafiltrate by means of an agar diffusion technique. Pharmacokinetic parameters were calculated by a computer program based on a two compartment model. We found that the elimination half-life of azlocillin ranged between 218.8 and 342.8 min, a result comparable to those of other investigators, who found similar elimination half-lives in anuric patients. During an observation period of 270 min, only 0.2-1.1% of the total dose of azlocillin was eliminated by way of the hemofilter. Apparently, continuous arteriovenous hemofiltration has no clinically relevant implications for the dosage or the dosage intervals of this antibiotic. On the other hand, azlocillin was taken up by the amicon Dia 20 hemofilter during the infusion. After the infusion was stopped the filter released azlocillin to blood and ultrafiltrate. The ratio of concentration in ultrafiltrate to plasma concentration in the afferent loop of the hemofilter was higher for about 45 min during the elimination phase than during the infusion. The volume of distribution was much larger (mean 28.5 l) than that found by other investigators. Therefore, the amicon-Dia 20 hemofilter seems to function as an additional distribution space.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2192574 TI - [Control of the placement of a central venous catheter using Doppler ultrasound]. AB - Precise placement of central venous catheters is necessary to prevent complications and assure proper functioning. Chest X-ray is the current standard method of locating the catheter tip. This is usually not feasible in the operating room setting, particularly after the induction of anesthesia. Intravascular ECG registration using the catheter as a lead and identification of intra-atrial P-waves has been suggested as an alternative. In the present study we evaluated the use of Doppler sonography as a noninvasive method of locating the catheter tip and detecting faulty placement. Two hundred patients scheduled for insertion of a central venous catheter took part in this study. The catheters were inserted via standard routes (internal or external jugular vein, basilar or cephalic vein). A Doppler sonographic device with a 2 mHz probe was used (Parke Electronics 915L). The probe was applied to the right sternal border and affixed at the position where the characteristic venous flow sound was most distinct. The signals were displayed visually, subjected to spectral analysis, and also recorded for later evaluation. A rapid injection of 2-5 ml isotonic saline causes turbulences which can readily be heard and recognized without special training. The position of every catheter was later confirmed by radiography, and in 159 patients the intraatrial ECG method was subjected to direct comparison with the sonographic method. The turbulences due to the injected fluid were found to cause an increased amplitude at frequencies above 350 Hz. If the catheter tip was positioned correctly there was no discernable time lag between the start of the injection and perception of turbulences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2192575 TI - [Dr. M. Zindler--70 years old]. PMID- 2192576 TI - An alternative quenched fluorescence substrate for Pz-peptidase. AB - 7-Methoxycoumarin-3-carboxylyl-Pro-Leu-Gly-Pro-D-Lys(2,4-dinitr oph enyl) is introduced as a new quenched fluorescence substrate for assaying Pz-peptidase (also known as soluble metallo-endopeptidase and endo-oligopeptidase). The value of Km for partially purified Pz-peptidase from rat muscle was 8.6 microM. High protein concentrations did not interfere with the assay, so that for the first time continuous assays of Pz-peptidase in crude tissue extracts became possible. PMID- 2192577 TI - Labeled antigen capture assay: a method for detecting monoclonal antibodies to cloned gene products. AB - We report here a relatively easy and highly sensitive assay for detecting monoclonal antibodies to the product of virtually any cloned gene. The protocol, termed labeled antigen capture assay (LACA), is a solid-phase type radioimmunoassay which uses a bacteriophage T7 expression system to generate exclusively radiolabeled antigen. Thus, to generate radiolabeled antigen for screening, the gene encoding the protein of interest need only be subcloned downstream of a T7 promoter, and the new construct transformed into an Escherichia coli strain harboring a compatible plasmid which encodes a thermal inducible copy of the T7 RNA polymerase. Expression of the T7-promoted gene in the presence of rifampicin and [35S]cysteine (or methionine) yields labeled antigen, which is then "captured" by specific monoclonal antibody and detected by autoradiography. Our results indicate that as little as 30 ng of specific monoclonal antibody can be detected using the LACA protocol. The protocol is applicable to the product of any cloned gene but is particularly useful in the case where the biochemical properties of the gene product of interest are unavailable. In this report we use the LACA protocol to screen a hybridoma library for monoclonal antibodies to the STb heat-stable enterotoxin (STb) of E. coli. Mice were immunized with a genetically constructed, affinity-purified Protein A-STb hybrid protein, and following spleen cell fusion and HAT selection, hybridomas were screened by the described LACA protocol for production of STb specific monoclonal antibody. Of over 1500 hybridomas tested 138 were positive, by primary LACA screening, for STb-specific IgG monoclonal antibodies. PMID- 2192578 TI - A highly sensitive fluorometric assay for sialyltransferase activity using CMP-9 fluoresceinyl-NeuAc as donor. AB - This paper presents a very sensitive fluorometric assay for sialyltransferase activity based on the transfer of 5-acetamido-9-deoxy-9-fluoresceinylthioure idoneuraminic acid onto distinct glycoproteins, thus allowing determination of acceptor specificities. Acceptor protein-bound fluorescence was quantified after gel filtration which separated fluorescent sialoglycoprotein from the fluorescence-labeled CMP-glycoside donor. Kinetic constants obtained for five different purified sialyltransferases indicated that CMP-9-fluoresceinyl-NeuAc was a suitable donor substrate for each enzyme, affording low Km values and Vmax values comparable in magnitude (15-100%) to that obtained with the parent CMP NeuAc. Sensitivity was enhanced 200- to 1000-fold compared to the radiometric sialyltransferase assay as it is used routinely. The method was applied to determination of the kinetic properties of purified rat liver alpha 2,6 sialyltransferase with four separate glycoprotein acceptors differing in glycan structure, employing very small amounts of donor, acceptor, and enzyme, and to the study of sialyltransferase activity of the human promyelocytic cell line HL 60 toward three different acceptors. PMID- 2192579 TI - Determination of epsilon (gamma-glutamyl)lysine crosslink in proteins using phenylisothiocyanate derivatization and high-pressure liquid chromatographic separation. AB - A sensitive, reproducible high-performance liquid chromatographic method is reported for the determination of the epsilon (gamma-glutamyl)lysine isopeptide bond, which is usually formed by protein-crosslinking transglutaminases between polypeptide chains. The procedure is based on the separation and quantitation of epsilon (gamma-glutamyl)lysine isodipeptide following exhaustive proteolytic digestion of the crosslinked peptide. It involves preliminary separation steps on a cation exchanger resin and a silica HPLC column, precolumn derivatization with phenylisothiocyanate, and reversed-phase high-pressure liquid chromatographic separation on a C18 column. The derivatized isodipeptide gave a linear concentration-response relationship, with a detection limit of 10 pmol/mg of protein. The combination of the preliminary separation steps and the sensitive detection system permits the determination of the epsilon (gamma-glutamyl)lysine crosslink in complex biological systems including total tissue homogenates. PMID- 2192580 TI - Application of a fusion protein, metapyrocatechase/protein A, to an enzyme immunoassay. AB - A fusion protein of metapyrocatechase and protein A was genetically produced for demonstration of effective conjugation of an enzyme with a binding protein employed in enzyme immunoassay. Plasmid pMPRA3, constructed by inserting the protein A gene into a plasmid pMK12 vector derived directly from the structural gene of metapyrocatechase, was expressed in Escherichia coli. The resulting fusion protein was shown to have promising properties for use in enzyme immunoassays due to the specific binding of the protein A moiety to the Fc portion of immunoglobulin G and to the high amplification of enzyme. Bovine serum albumin, a model antigen, was successfully determined in the concentration range from 1 x 10(-3) to 1 x 10(-7) g/ml. PMID- 2192581 TI - A turbidimetric method for measuring fibrin formation and fibrinolysis at solid liquid interfaces. AB - We have developed a rapid and sensitive method by which to quantitate proteolysis of fibrin(ogen) at interfaces. Microscopic polystyrene-divinylbenzene beads coated with a mixed monomolecular film of lecithin and fibrinogen aggregate in aqueous media following exposure to thrombin or enzymes of thrombin-like activity. This aggregation is a consequence of interbead association of fibrin. As an indirect measure of the rate of fibrin formation, the rate of aggregation of beads can be used advantageously to assay enzymes and enzyme regulators pertinent to coagulation. Since the apparent absorbance of monodisperse beads is greater than that of bead aggregates, determination of the rate of change of apparent absorbance of a stirred dispersion of beads following addition of enzyme or enzyme-regulator mixture is a convenient and simple means by which to quantitate the rate of bead aggregation. Using a simple spectrophotometer or aggregometer, the method can be used to quantitate as little as 0.0005 NIH unit of thrombin. Aggregates of fibrin-coated beads can be disaggregated by several proteinases, most notably plasmin. Thus, just as bead aggregation can be used to quantitate effectors of fibrin formation, dissociation of aggregates of fibrin coated beads can be used to quantitate effectors of fibrinolysis. Using disaggregation as a measure of fibrinolysis, the method is sensitive to as little as 0.005 unit of plasmin. Fibrin(ogen)-coated beads should prove a useful tool for studying proteolysis of fibrin(ogen) in general, and adsorbed fibrin(ogen) in particular. PMID- 2192582 TI - A primate bioassay for the determination of renin inhibitory peptides in serum. AB - The study of renin inhibitory peptides (RIPs) in rodents and primates requires the establishment of a simple, high volume method for determining the concentration of RIPs in serum after intravenous or oral dosing. The human renin inhibition assay useful for rodents is not directly applicable to primates due to inherent production of angiotensin I from the primate serum angiotensinogen and added recombinant human renin. Therefore, a novel approach to analyze the serum concentrations of RIPs in primates is described based on in vitro studies with monkey serum. The procedure involves the inactivation of monkey angiotensinogen and monkey renin by thermal denaturation prior to analysis. Application of this assay was demonstrated by analyzing serum samples from an in vivo study in monkeys using ditekiren (U-71,038), a renin inhibitory peptide, and by validation of the assay and results using a tritium-based radioimmunoassay (RIA) for ditekiren. The minimum detectable limit of ditekiren for both the RIA and the bioassay for primates was 10ng/ml serum. The reported bioassay should be of value for monitoring serum levels of thermostable RIPs from pharmacokinetic, bioavailability, and pharmacodynamic studies in primates as well as in humans. PMID- 2192583 TI - Characterization of polymerase chain reaction amplification of specific alleles. AB - Under certain conditions, polymerase chain reaction (PCR) can be used to differentially amplify one allele over another. To characterize the phenomenon, we have made a series of PCR primers and determined whether differential amplification could be detected after agarose gel electrophoresis. Two allele pairs were examined; one pair represents a transversion and one pair represents a transition. The following conclusions emerge: (i) when the 3' or the 3' penultimate base of the oligonucleotide mismatched an allele, no amplification product could be detected; (ii) when the mismatches were 3 and 4 bases from the 3' end of the primer, differential amplification was still observed, but only at certain concentrations of magnesium chloride; (iii) the mismatched allele can be detected in the presence of a 40-fold excess of the matched allele; (iv) primers as short as 13 nucleotides were effective; and (v) the specificity of the amplification could be overwhelmed by greatly increasing the concentration of target DNA. PMID- 2192584 TI - Deep venous thrombosis: an overview. AB - The patients at high risk of deep venous thrombosis are defined. Factors in the formation of intravenous thrombi are described. The roles of endothelium, formed elements, clotting factors, and their interrelationships are correlated. Diagnostic modalities and their application are described, and the commonly used medical and surgical therapies are specifically outlined. PMID- 2192585 TI - Effect of captopril on plasma prolactin in patients with essential hypertension. AB - The effects of the angiotensin-converting enzyme inhibitor captopril on blood pressure, heart rate, plasma prolactin, and renin activity were examined in a single-blind, placebo-controlled trial on 30 patients with essential hypertension (15 given drug, 15 placebo). Captopril, 25 mg administered orally, reduced the blood pressure and increased the plasma renin activity. Captopril decreased mean plasma prolactin from 17.5 +/- 1.4 ng/mL to 9.1 +/- 1.0 ng/mL (p less than 0.001). Significant correlation was found between captopril-induced change from control values of plasma prolactin (delta plasma prolactin) vs delta plasma renin activity (r = -0.688, p less than 0.001). These results suggest that acute administration of captopril was accompanied by a reduction in plasma prolactin and that this reduction may be of clinical significance during therapy of hypertension. PMID- 2192586 TI - Marfan's syndrome and coarctation. Coincidence or association? A case report. AB - The case of a patient with coexisting Marfan's syndrome and coarctation of the aorta is presented. The relevant literature is reviewed and the possible association between the two lesions is discussed. PMID- 2192587 TI - Dynamics of mitosis and cleavage. PMID- 2192588 TI - Attachment of one spindle pole to the cortex in unequal cleavage. PMID- 2192589 TI - Actin and myosin biochemistry in relation to cytokinesis. PMID- 2192590 TI - Cleavage furrow formation and actin-modulating proteins. PMID- 2192591 TI - Role of the mitotic apparatus in furrow initiation. PMID- 2192592 TI - Actomyosin organization in mitotic Dictyostelium amoebae. AB - Immunofluorescence localization of actin and myosin during mitosis indicates the significant roles of these cytoskeletons for cytokinesis. High frequency mitosis was induced by synchronous culture using temperature shift (T. Kitanishi-Yumura and Y. Fukui, 1987), and high resolution fluorescence microscopy was performed by the agar-overlay method (S. Yumura and Y. Fukui, 1984). It was shown that actin and myosin are dissociated from the cortex in prophase and reassembled in anaphase to form unique cortical structures: the contractile ring and/or polar lamellipodial network. Conventional myosin (myosin-II) is only localized in the contractile ring, whereas a low-molecular weight isozyme (myosin-I) is localized in the polar leading edge (Y. Fukui, T. Lynch, H. Brzeska, and E. Korn, 1989). Actin is localized in both structures and also forms a unique array in the furrow oriented perpendicular to the plane of constriction (Y. Fukui and S. Inoue, manuscript in preparation). The study suggests that conventional myosin provides the major force of constriction, whereas myosin-I participates in projecting lamellipodia, and actin is involved in several different functions in different regions of the cytoplasm. PMID- 2192593 TI - Analysis of furrow formation and furrowing during cell division in Tetrahymena using cell-division-arrest mutants. PMID- 2192594 TI - Association of actin and myosin in the contractile ring. PMID- 2192595 TI - Use of fluorescently labeled probes to analyze cell division in living cells. PMID- 2192596 TI - Mechanical properties of the cortex before and during cleavage. AB - The changes in stiffness of the cell before and during cleavage reported previously for various kinds of echinoderm eggs are classified into three types. There is no general rule that cleavage starts when the stiffness attains a maximum or a minimum. Because the stiffness of the cell surface is much greater than that of the mitotic apparatus, the change in stiffness of the cell represents mainly the change in stiffness of the cell surface. The tension at the cell surface changes in parallel over the entire surface before the onset of cleavage. After the onset of cleavage, the tension at the furrow surface becomes greater in the direction parallel to the furrow than perpendicular to it. A remarkable change in mechanical properties occurs at the furrow surface simultaneously with the onset of cleavage. Judging from the temporal and spatial coincidence between this change and the formation of the contractile ring reported previously in sea urchin eggs at the onset of cleavage, it is concluded that this change is due to the formation of the contractile ring that generates the motive force for cleavage. PMID- 2192597 TI - Cytokinesis in the early Drosophila embryo. PMID- 2192598 TI - Contractile proteins in Drosophila development. AB - In summary, we have used a multidisciplinary approach to the analysis of actomyosin-based motility during Drosophila embryogenesis. We have documented the movements of early embryogenesis with modern, video methods. We have characterized the cytoplasmic myosin polypeptide, made specific polyclonal antisera to the molecule, studied its distribution during early embryogenesis, cloned and partially characterized the gene that encodes it, and have recently completed the nucleotide sequence of a nearly full length cDNA that encodes the entire protein-coding region. We have initiated studies on myosin function in living embryos both by direct microinjection of antibodies and through classical genetics. To better understand how myosin function is regulated, we have begun analysis of its light chains. Finally, to investigate the molecular mechanism by which its function is integrated into a labile cytoskeleton, whose architecture is constantly changing, we have also investigated Drosophila spectrins. Together, these studies are designed to shed light on the dynamics of biologic form at the cellular level, with current focus on such complex processes as cytokinesis and morphogenesis. PMID- 2192599 TI - Cytokinesis by furrowing in diatoms. AB - We have found that nocodazole reversibly inhibits nuclear migration and can be used to induce karyokinesis before the completion of nuclear migration, resulting in spindles that are displaced toward the hypothecal end of the cell. Surprisingly, displacement of mitotic nuclei results in complete spatial uncoupling of karyokinesis from cytokinesis. Nocodazole-induced displacement of mitotic nuclei will neither alter the position of the original furrow nor induce additional furrows. This demonstrates that in S. turris the location of the presumptive cleavage furrow is not determined by the position of the spindle but is cortically determined before mitosis. Therefore, although cell division in S. turris resembles certain mechanochemical aspects of cleavage in animal cells, our evidence suggests that the spatial regulation of the cytokinetic apparatus relies on a mechanism of cortical determination that is characteristic of plant cells. PMID- 2192600 TI - Polar body formation in Tubifex eggs. PMID- 2192601 TI - Cortical and cytoplasmic phases in amphibian eggs. PMID- 2192602 TI - Laterally mobile, cortical tension elements can self-assemble into a contractile ring. AB - Animal cells cleave by the progressive constriction of an equatorial region. The plane of the constricting equator is orthogonal to the mitotic spindle axis and is positioned so that the spindle is bisected, thus ensuring equipartitioning of the chromosomes. Constriction is achieved by the active contraction of a circumferential band of actomyosin-containing filaments. The mitotic apparatus is necessary for the formation of the contractile ring and specifies its position and orientation; however, it takes no active part in furrowing. One of the central questions that has to be answered to understand cytokinesis is: how does the mitotic apparatus act to organize the contractile ring? It has been suggested that the mitotic apparatus acts to modulate locally the force generated by the cortical contractile filaments. The resultant gradients of cortical tension cause filaments to be pulled into regions of higher tension. The geometry of the stimulus from the mitotic apparatus is such that the highest levels of tension occur in the equatorial regions. The geometric distortions that take place when contractile filaments are pulled into this region cause them to become partially oriented circumferentially. When furrowing commences, mechanical forces act to align the filaments further and concentrate them in a narrow band. The furrow therefore becomes self-sharpening. Similar lateral flows of contractile filaments may occur during cell locomotion and growth cone extension. PMID- 2192603 TI - Testing cleavage mechanisms by comparing computer simulations to actual experimental results. PMID- 2192604 TI - The contractile ring and furrowing in dividing cells. PMID- 2192605 TI - Vitamin B6 and decarboxylation of histidine. PMID- 2192606 TI - Vitamin B6 metabolism by human liver. AB - The B6 vitamers (pyridoxine, pyridoxamine, and pyridoxal) are primarily metabolized in liver to pyridoxal 5'-phosphate (PLP) and the deadend catabolite 4 pyridoxic acid. We have built on the elegant early work of Snell and others to describe the activities of the human liver enzymes responsible for vitamin B6 metabolism and to develop a model of the relative rates of these interconversions in vivo. This model is consistent with changes in plasma B6 after a load, the clearance of different vitamers (e.g., pyridoxine versus pyridoxal), and with the low plasma PLP in patients with cirrhosis. Because cirrhotics were found to be capable of PLP synthesis, we have used oral supplementation with pyridoxine to restore plasma PLP to the normal range, and have evaluated the effects of this intervention on amino acid metabolism. No significant differences were observed in plasma or urinary clearance of methionine (or cystathionine) after an oral load, nor in amino acid clearance from circulation after a protein load for cirrhotic patients before and after restoration of normal plasma PLP. Hence, the abnormal metabolism of vitamin B6 does not appear to be an important factor in the deranged amino acid metabolism in this disease. Nonetheless, this approach may be generally useful in assessing the importance of PLP in other abnormalities. PMID- 2192607 TI - Glutamine transaminase K and cysteine conjugate beta-lyase. PMID- 2192609 TI - On the transamination of enzymes. PMID- 2192608 TI - Neurobiology of pyridoxine. PMID- 2192610 TI - Neuronal dopa decarboxylase. PMID- 2192612 TI - Role of pyridoxine in oxalate metabolism. PMID- 2192611 TI - Hippocampal zinc thionein and pyridoxal phosphate modulate synaptic functions. AB - The hippocampus, a component of the limbic system, is a prominent subcortical structure, which not only contains high concentrations of zinc, but also exhibits regional variations in this essential element, with concentrations being highest in the hilar region and lowest in the fimbria. For example, the concentration of zinc in the mossy fiber axons has been estimated to approach 300-350 microM. Both zinc and pyridoxal phosphate (PLP) deficiency and excess have been reported to produce epileptiform seizures, which are blocked by gamma-aminobutyric acid (GABA). The proposed mechanism is that at physiological concentrations zinc stimulates the activity of the hippocampal pyridoxal kinase (50% stimulation at 1.7 x 10(-7) M), enhancing the formation of PLP, whereas in pharmacological doses zinc inhibits the activity of glutamate decarboxylase (GAD) directly (50% inhibition at 6.5 X 10(-4) M) by preventing the binding of PLP to HoloGAD. Furthermore, recent studies have shown that two forms of GAD are found in the rat brain. One form (GAD A) does not require PLP for maximal activity, while another form (GAD B) does. Furthermore, the ratio between GAD A and GAD B is nonuniform throughout brain areas, and the hippocampus contains twice as much GAD B (the PLP requiring GAD) as GAD A. Although the hippocampus is a common target of exogenous neurotoxic agents, "free" zinc in greater than physiological concentrations should be considered an endogenous central neurotoxin. For example, iontophoretically applied zinc in the frontoparietal cortex enhances and prolongs the firing rate of neurons in urethane-anesthetized rat. In addition, zinc (50 500 microM) significantly depresses the paired-pulse potentation in the hippocampal CA3 subfield. Moreover, zinc selectively blocks the action of N methyl-D-aspartate on cortical neurons and enhances the quisqualate receptor mediated injury. Finally zinc competitively inhibits the calcium-dependent release of transmitter by inhibiting the entry of Ca2+ into the nerve terminals. Since zinc in a concentration of 300-350 microM could not possibly remain "unbound" in the hippocampus, we searched for and identified a metallothionein like protein (MT) in the bovine hippocampus, which produces two isoforms on reverse-phase HPLC and lacks aromatic amino acids, but possesses metallomercaptide bonds. We believe that the hippocampal metallothionein, by donating zinc to an extensive number of zinc-activated, PLP-mediated biochemical reactions, modulates synaptic functions. Furthermore, by virtue of its inducibility, metallothionein binds additional amounts of zinc, maintains its steady-state concentration, prevents inhibition of an extensive number of sulfhydryl-containing enzymes and receptor sites, and hence averts metal-related neurotoxicity. PMID- 2192613 TI - The relationship between vitamin B6 metabolism, asthma, and theophylline therapy. PMID- 2192614 TI - Successful therapy with vitamin B6 and vitamin B2 of the carpal tunnel syndrome and need for determination of the RDAs for vitamins B6 and B2 for disease states. PMID- 2192615 TI - Mammalian aspartate aminotransferase isozymes. From DNA to protein. PMID- 2192616 TI - Vitamin B6 safety issues. PMID- 2192617 TI - Evolutionary and biosynthetic aspects of aspartate aminotransferase isoenzymes and other aminotransferases. AB - The mitochondrial and cytosolic isoenzymes of aspartate aminotransferase are homologous proteins. Both are encoded by nuclear DNA and synthesized on free polysomes. The organization of their genes is very similar, five out of a total of eight introns are located at the same nucleotide position. A variant consensus sequence was observed at the 3' splice site of introns of genes of imported mitochondrial proteins which may reflect the existence of splicing factors specific for the genes of this particular group of nuclear-encoded proteins. To date the amino acid sequences of 22 aminotransferases are known. A rigorous analysis yielded clear evidence that aspartate, tyrosine, and histidinol phosphate aminotransferases are homologous proteins despite their low degree of sequence identity. The evolutionary relationship among the vitamin B6-dependent enzymes in general appears less clear. Conceivably, their common structural and mechanistic features are dictated by the chemical properties of pyridoxal 5' phosphate rather than being due to a common ancestor of their protein moieties. In agreement with this notion, the ubiquitous active-site lysine residue that forms a Schiff base with the coenzyme can be replaced in the case of aspartate aminotransferase by a histidine residue without complete loss of catalytic competence. PMID- 2192618 TI - Precursor forms of mitochondrial aspartate transaminase. PMID- 2192619 TI - The roles of S-adenosylmethionine and pyridoxal phosphate in the lysine 2,3 aminomutase reaction. PMID- 2192620 TI - Thermostable alanine racemase. Its structural stability. AB - The gene encoding thermostable alanine recemase from Bacillus stearothermophilus was cloned and expressed in E. coli. The enzyme was purified to homogeneity from cell extracts of E. coli carrying a plasmid designated pICR4. The alanine racemase gene sequenced was found to contain an open reading frame of 1158 nucleotides. The molecular weight of the enzyme subunit was estimated to be 43,341. The alpha-helical and beta-structure contents were calculated to be about 34 and 26%, respectively, from CD data. CD measurements of the denaturation process of enzyme by guanidine hydrochloride showed the presence of a stable intermediate during the denaturation. Limited proteolysis with subtilisin resulted in the formation of two dissimilar peptide fragments with molecular weights of about 28,000 and 13,000 in the early stage of the digestion. These suggest that the enzyme subunit is composed of two structurally dissimilar domains connected by a short polypeptide (residues 258-266), which first suffers the limited proteolysis. However, the enzyme retained almost full activity and the conformation indistinguishable from the intact protein even when it was proteolytically hydrolyzed to more than 10 fragments. PMID- 2192621 TI - Regulation of immune responses by vitamin B6. PMID- 2192622 TI - Metabolism of pyridoxine in hepatomas. PMID- 2192623 TI - Pyridoxal phosphate as a regulator of the glucocorticoid receptor. PMID- 2192624 TI - The influence of vitamin B6 on the structure and function of the glucocorticoid receptor. AB - Pyridoxal phosphate influences several properties of steroid hormone receptors in vitro, but its role in vivo has not been clearly established. In an effort to address this issue, we have investigated the in vivo effects of vitamin B6 on the physical properties and biological function of the human glucocorticoid receptor. We demonstrate that vitamin B6 treatment of whole cells in culture produces an alteration in the isoelectric point of the receptor, as well as changes in the steroid and DNA binding capacities. Furthermore, glucocorticoid dependent transcriptional activation properties of the receptor are also altered by modulation of the vitamin B6 status. High concentrations of vitamin B6 suppress activation of transcription, while vitamin deficiency enhances responsiveness to steroid hormone. Together, these studies imply a physiological role for vitamin B6 in glucocorticoid hormone action. PMID- 2192625 TI - Modeling inhibitors in the active site of aspartate aminotransferase. PMID- 2192626 TI - Coenzyme reorientations in the active sites of vitamin B6-dependent enzymes. PMID- 2192627 TI - Location and turnover of vitamin B6 pools and vitamin B6 requirements of humans. PMID- 2192628 TI - The bioavailability of vitamin B6. Recent findings. AB - Further clarification of the bioavailability of dietary vitamin B6 requires better analytical data concerning the forms of vitamin B6 in foods as well as the overall composition of foods. The application of radioisotopic and stable isotopic studies such as those described will provide useful information concerning the inherent bioavailability of the various vitamin B6 compounds. Additional studies should then address the influence of other dietary components on the utilization of the vitamin B6 compounds, using intrinsic and extrinsic enrichment techniques. Care must be taken in interpretation of the results of animal bioassays in the determination of the bioavailability of vitamin B6 in complex diets. PMID- 2192629 TI - Effect of aging on vitamin B6 status and metabolism. PMID- 2192630 TI - The physiological basis of milk secretion. PMID- 2192631 TI - Biochemical classification of patients with gross cystic breast disease. PMID- 2192632 TI - Review of GCDFP-15. An apocrine marker protein. PMID- 2192633 TI - Cellular ras protooncogene expression in human mammary explant cultures. A potential marker for chemical carcinogenesis. AB - The major findings of the present study can be summarized as follows: 1. The newly developed assay for quantitative determination of ras protooncogene expression which utilizes affinity labeling of ras p21 with [alpha-32P]GTP can effectively demonstrate the presence of ras protooncogene expression in explant cultures of human mammary tissues. 2. The prototype chemical carcinogens NMU and BP induce amplified expression of ras protooncogene in benign (noninvolved) human mammary TDLU. 3. The specific enhancement of ras expression by BP in TDLU (target tissue) but not in MF (nontarget tissue) for tumorigenesis indicates that the constitutive levels of ras protooncogene in the target tissue are responsive to carcinogenic insult. 4. The relative extent of ras protooncogene expression may constitute a sensitive marker for target tissue susceptibility to chemical carcinogenesis. PMID- 2192634 TI - A randomized trial of dietary intervention with essential fatty acids in patients with categorized cysts. AB - Two hundred women with breast cysts proven by aspiration were entered into a randomized double-blind trial of Efamol (evening primrose oil) at a dose of 6 capsules daily or equivalent placebo dose for a year. Cysts were categorized by initial electrolyte composition, and follow-up continued for 1 year posttherapy. Recurrent cyst formation in the first year was slightly (but not significantly) lower in the Efamol group compared with the placebo-treated group. The Efamol treatment was well tolerated as the dropout rate was only 7% and equal in both the active and placebo groups. The initial electrolyte composition did not predict for cyst recurrence. PMID- 2192635 TI - Pathways of hormone metabolism in normal and nonneoplastic breast tissue. PMID- 2192636 TI - Overview of problems and approaches in heart development. PMID- 2192637 TI - Elastogenic cells in the developing cardiovascular system. Smooth muscle, nonmuscle, and cardiac neural crest. PMID- 2192638 TI - Inductive interactions in heart development. Role of cardiac adherons in cushion tissue formation. PMID- 2192639 TI - Regulation of receptor function by protein phosphorylation. PMID- 2192640 TI - Development of gap junctions. PMID- 2192641 TI - Myofibrillar proteins in the developing heart. PMID- 2192642 TI - Origins and assembly of avian embryonic blood vessels. AB - Two processes by which embryonic blood vessels develop are well-known: angiogenesis (growth by budding and branching of existing vessels) and local formation of endothelial vesicles that coalesce with elongating vessels. The former process appears to be more prevalent, with the latter restricted to vessels that form near the endoderm-mesoderm interface. The contributions of endothelial cells formed by each of these processes to specific blood vessels has not been defined, however, nor have the origins of precursors (angioblasts) of intraembryonic endothelial populations been established. To identify the origins of endothelial cells, precursor populations from quail embryos were transplanted into chick embryos. Antibodies that recognize quail endothelial cells were applied to sections from chimeric embryos fixed 2-5 days after surgery. These experiments reveal that all intraembryonic mesodermal tissues, except the notochord and prechordal plate, contain angiogenic precursors. Many angioblasts emigrate from the grafted tissue, invading surrounding mesenchyme and contributing to the formation of arteries, veins, and capillaries in a wide area. The invasive behavior of these angioblasts is unlike that of any other embryonic mesenchymal cell type and represents a third process operating during embryonic blood vessel formation. Transplanted angioblasts, even those excised from quail trunk regions, form normal craniofacial vascular channels, including the cardiac outflow tract. These results demonstrate that the control over blood vessel assembly resides within the connective tissue-forming mesenchyme of the embryo, not within endothelial precursors. PMID- 2192643 TI - Cardiac mapping of regional glucose utilization in fetal cats, rabbits, and chicks using [14C]2-deoxyglucose. PMID- 2192644 TI - Development of the outflow tract. A study in hearts with situs solitus and situs inversus. PMID- 2192645 TI - The instructive role of fibronectins in cell migrations during embryonic development. PMID- 2192646 TI - Cardiovascular defects associated with alcohol, retinoic acid, and other agents. PMID- 2192647 TI - Alteration of cardiogenesis after neural crest ablation. PMID- 2192648 TI - Altered development of pharyngeal arch vessels after neural crest ablation. PMID- 2192649 TI - Hemodynamics of the developing cardiovascular system. PMID- 2192650 TI - The role of basement membranes in vascular development. AB - Endothelial cells produce and bind to multiple basement membrane components. Fibronectin and interstitial collagens seem to promote migration and proliferation, whereas basement membrane collagen and laminin stimulate attachment and differentiation. Human umbilical vein endothelial cells will rapidly form capillary-like structures when plated on a reconstituted basement membrane gel. This morphological differentiation involves the alignment of the cells followed by their close association with one another and the formation of a central lumen. Using antibodies to basement membrane components, we find that the formation of these vessels is a complex process involving multiple interactions with several matrix components. Synthetic peptides to active sequences in laminin have demonstrated that at least two sites in laminin participate in tube formation. An RGD-containing site on the A chain appears to mediate cell to matrix adhesion, and synthetic RGD-containing peptides block cell to matrix adhesion during tube formation. A YIGSR-containing site on the B1 chain appears to mediate cell to cell adhesion and promote tube formation because synthetic peptides block the strong cell interactions involved in tube formation. Our data with laminin peptides show that for at least one protein, multiple sites are recognized. Such data would also suggest that several cellular receptors are involved in a concerted process in laminin-induced differentiation of endothelial cells. We conclude that vessel formation is a complex, multistep process. Identification of active sites that block this process may have potential use in blocking angiogenesis in diseases such as diabetic retinopathy and Kaposi's sarcoma. PMID- 2192651 TI - Introduction to congenital heart disease. PMID- 2192652 TI - Strategies and challenges in metabolic engineering. PMID- 2192653 TI - Effects of promoter induction and copy number amplification on cloned gene expression and growth of recombinant cell cultures. PMID- 2192654 TI - Optimal induction of protein synthesis in recombinant bacterial cultures. PMID- 2192656 TI - Genetic engineering of metabolic pathways applied to the production of phenylalanine. PMID- 2192655 TI - Expression, purification, and immobilization of a protein A-beta-lactamase hybrid protein. PMID- 2192657 TI - Novel membrane-based immobilization technique for bioreactors. PMID- 2192658 TI - Studies of transport processes coupled with reaction in membrane-sandwiched yeast cell reactors. PMID- 2192659 TI - Mechanisms of oxygen transfer enhancement during submerged cultivation in perfluorochemical-in-water dispersions. PMID- 2192660 TI - Nutrient transport and cellular morphology in immobilized cell aggregates. PMID- 2192661 TI - Large-scale growth of Bordetella pertussis for production of extracellular toxin. PMID- 2192662 TI - Growth kinetics of free and immobilized insect cell cultures. PMID- 2192663 TI - Bioreactor development for production of viral pesticides or heterologous proteins in insect cell cultures. AB - The insect cell-baculovirus expression system has significant potential for producing proteins requiring some degree of posttranslational modification. T. ni cells appear to be as good a host as S. frugiperda cells for heterologous protein production as demonstrated by production of beta-galactosidase. Attachment dependent cells of T. ni can be effectively cultured in a packed-bed reactor using glass beads. When cell in such a reactor were infected, they produced 35% of the total protein as beta-galactosidase. No cell detachment was observed even 70 h postinfection. A model of viral entry has been proposed and tested. PMID- 2192664 TI - Improvement of plasmid stability by immobilization of recombinant microorganisms. PMID- 2192665 TI - L-aspartic acid production using immobilized E. coli cells in a packed-bed reactor. Design of reactor and its optimal operation. PMID- 2192666 TI - Analysis of performance limitations in immobilized cell fermentors. PMID- 2192667 TI - Methods for cloning key primary metabolic enzymes and ancillary proteins associated with the acetone-butanol fermentation of Clostridium acetobutylicum. AB - The unavailability of genetically defined mutants for complementation has intensified the problems inherent in cloning genes from C. acetobutylicum. The uniqueness of some of the pathways of this organism coupled with the relative inefficiency of transformation of clostridia and few characterized mutants in these pathways have made cloning these genes by traditional complementation methods impractical. Oligonucleotide hybridization techniques have been shown to circumvent many problems involved in detecting protein expression. The ease of hybridization screening of plaques allows phage libraries to be examined more readily than is generally the case with colony screening techniques. Recombinant lambda phages also contain more DNA per insert than most plasmid vectors can maintain, thus further decreasing the amount of screening necessary. Cosmid libraries, offering even greater length of individual inserts, can be screened in a similar manner, although such screening incorporates the limitations of colony screening techniques. It is true that the technique hinges on the ability to obtain an amino acid sequence from which an oligonucleotide can be designed. In the past, the ability to obtain sequences was limited because the quantity and number of purified proteins were limited or the proteins were amino-terminally blocked. However, recent technological advances in this area, such as high resolution gel separation techniques coupled with microsequencing, have opened the door to proteins previously inaccessible. Deformylation methods have been developed to deblock amino-terminally formylated proteins, and successful internal amino acid sequence analysis by in situ protease digestion has also been reported using only picomolar quantities of proteins separated by one- or two dimensional gel electrophoresis. Protein and DNA sequence data banks have been significantly upgraded in the past few years. A proposed oligonucleotide sequence can be evaluated to determine what other possible sequences have similar homology; moreover, protein similarity comparisons between related species might possibly supplant the need for protein isolation if regions of highly conserved amino acid sequences are found. To our knowledge, this represents the first reported use of oligonucleotide probe hybridization screening technology as a strategy for cloning solvent pathway genes of C. acetobutylicum. Despite the deleterious effects on hybridization inherent in the high A + T content of C. acetobutylicum gene specific-directed oligonucleotides, the technique has been shown to function with few modifications to previously recorded systems. PMID- 2192668 TI - Effects of culture conditions on plasmid stability and production of a plasmid encoded protein in batch and continuous cultures of Escherichia coli JM103[pUC8]. PMID- 2192669 TI - Sir Hugh Lockhart-Mummery Memorial Meeting. 9 February 1990. PMID- 2192670 TI - Pathology of Crohn's disease. PMID- 2192671 TI - Anal lesions in Crohn's disease. PMID- 2192672 TI - The management of acute anorectal sepsis. PMID- 2192673 TI - Antibiotics in colorectal surgery. PMID- 2192674 TI - The challenge of the bile duct in 1990. PMID- 2192675 TI - Fifty years of local excision for rectal carcinoma. PMID- 2192676 TI - Venous disease: investigation and treatment, fact or fiction? AB - This review looks at some clinical and experimental methods and treatments used in venous disease, and attempts to dispel some myths which have been associated with it. Over the last century numerous techniques have been introduced to aid the understanding of the physiology of normal legs and the pathophysiology of those with venous disease. Tourniquet testing along with clinical examination remains the only method of venous assessment in most hospitals. Venous ulceration in the past has been associated with deep vein incompetence, but the newer, non invasive techniques of Doppler ultrasound and duplex examination are now identifying patients with leg ulceration who have superficial venous insufficiency and therefore a surgically correctable condition. Perforating veins and their possible role in the aetiology of venous ulceration along with invasive and non-invasive methods for their detection is reviewed. Some of the conservative compression treatments and dressings available for the treatment of venous ulceration are discussed. It is concluded that adherence to sound surgical principles remains the mainstay of the successful management of patients with venous disease. PMID- 2192678 TI - [Conservative treatment of cancer of the rectum]. PMID- 2192679 TI - [Endoscopic ultrasonography of the bile ducts]. PMID- 2192677 TI - Resection of liver metastases from a colorectal carcinoma does not benefit the patient. AB - This paper presents arguments for and against the motion that 'Resection of liver metastases from colorectal carcinoma does not benefit the patient'. The case for this proposition is summarised as follows: survival after resection of small metastases is not markedly different from the natural history of similar tumours; patients with metastases apparently localised to one area of the liver are uncommon, and thorough investigation further reduces the proportion of such patients; the operative mortality of liver resection has a significant adverse effect on survival after resection, and may cancel out the benefits of surgery, and finally the alternative non-operative methods of treating these patients may offer similar benefits to resection. The counter argument is simple: for a patient with liver metastases the only hope of eradication of liver disease lies in surgical resection. If this can be achieved then the prognosis is as good as for a similar primary tumour without liver metastases. PMID- 2192680 TI - [Perforated ulcer. The first episode of ulcer. Vagotomy? What type?]. PMID- 2192682 TI - [Esophagorespiratory tract fistula treated by primary suture. Apropos of 2 cases of esophago-pleural fistula and 2 cases of esophagobronchial fistula]. AB - We describe two oesophago-pleural fistulas arriving respectively 40 months and 15 years after pneumonectomia, and two oesophago-bronchial fistulas due to perforated oesophageal diverticula. We evaluate diagnostic methods and discuss etiology of these oesophageal fistulas. Pleural fistulas treatment associate thoracic drainage, direct surgical treatment of the fistula with primary suturing of oesophagus. For oesophago-bronchial fistula treatment, we have made pneumonectomia one time and primary bronchial suturing another. In these two cases, oesophagus was only sutured without pleural or muscular flap. Transient alimentary gastrostomy was made. No fistula recidive of postoperative complication occurred. There is no operative mortality. PMID- 2192681 TI - [Epithelial cancer of the ovary in adults: prognostic and therapeutic study of 95 cases]. AB - The authors report 95 cases of ovarian carcinoma treated between 1st January 1975 and December 1986 in the department of gynecology and radiotherapy of hospital Bretonneau in Tours. The overall actuarial 5-year survival was 37.5%, for stage I 100%, stage II 51%, stage III 36%, stage IV 5%, grade I 88%, grade II 51%, grade III 18%. The authors stress the prognostic importance of histologic grade and the bad prognosis of small cell ovarian carcinoma with hypercalcemia. The authors propose a therapeutic attitude based on the results and a review of the literature. PMID- 2192683 TI - [Hydatic cyst of the psoas muscle. Apropos of 3 cases]. AB - In the three patients, the localization and the hydatic origin have been determined by preoperative ultrasonography in two instances, the diagnosis was confirmed by CT scan. Ultrasonography and computed tomography allowed a direct and simple surgical approach of the cyst. PMID- 2192684 TI - [Mesenteric cystic lymphangioma in children. Apropos of a case revealed by anemia]. AB - A case of mesenteric cystic lymphangioma revealed by hypochromic anemia and abdominal pain, secondary to an intracystic hemorrhage is reported in a 4-year old child. Etiology, pathology, diagnosis, treatment and prognosis of mesenteric lymphangioma in children are reviewed. PMID- 2192686 TI - Planning an educational activity. From idea to implementation. PMID- 2192685 TI - Ultrasonographic detection of metastatic axillary lymph nodes in breast cancer. AB - Metastatic involvement of the axillary lymph nodes is the most important prognostic factor in breast cancer. Preoperative knowledge of lymph node status would be useful in planning the therapy for breast cancer. The aim of our study was to find how accurately metastatic lymph nodes can be detected with ultrasonography (US). Our study consisted of 63 breast cancer patients having 65 breast cancers. Their axillae were examined preoperatively with US (with a 7.5 Mhz linear-array transducer). 27.7% of these patients had metastatic axillary lymph nodes. With US we could detect 12 of these 18 axillary metastases. In 2 of our 6 false negative results only micrometastases were found on histological examination. In our study the sensitivity of US was 66.6%. There was only one axilla, in which nodes were detected with US, but on histological examination no metastases were found, thus giving a specificity of 97.9%. Our study indicates that in the axilla normal nodes are not visible with US. PMID- 2192687 TI - Growth of bacteria in prefilled syringes stored in home refrigerators. AB - Insulin was examined for the rate of bacterial growth after being stored in prefilled syringes in home refrigerators and in a controlled laboratory refrigerator. Home refrigerators were used to simulate conditions that exist in client homes to establish the safety of storing insulin in prefilled syringes in uncontrolled environments. Insulin from each source was inoculated on three different media and incubated at three temperatures in three oxygen environments. A total of 768 cultures were examined. It was found that temperature had a significant effect on the incidence of bacteria. The difference in incident of bacteria between syringes stored in the controlled versus uncontrolled environments was not statistically significant. PMID- 2192688 TI - Gaining and maintaining research entree in the nursing home. PMID- 2192689 TI - Lung function testing in infancy. PMID- 2192690 TI - Rehabilitation of head injured children. PMID- 2192691 TI - Hope: a relevant concept for geriatric psychiatry. AB - The focus in psychiatry has been on treating people for hopelessness, as opposed to understanding more about maintaining hope. This study reports findings from a study of hope conducted with community-based older adults. A general linear model procedure was used to more clearly understand the relationships among hope and other relevant variables. This model is used as a basis for proposing an intervention model for maintaining hope in older adults. PMID- 2192692 TI - Burden of mental illness on the family: a critical review. AB - The burden that a family experiences as a result of one of its members having a chronic mental illness has been the subject of research since the mid-1950s. A review of the findings in the research literature, an examination of the conceptual and operational definitions of burden, and an evaluation of methodological issues are provided. Finally, based on this critical review, suggestions are offered for future research. PMID- 2192694 TI - Free-floating deep venous thrombosis. A retrospective analysis. AB - Duplex scan to diagnose deep venous thrombosis is an established technique. As experience accumulated, patients with free-floating thrombi were identified. A retrospective review of 65 patients was performed to study these thrombi, to evaluate treatment regimens, and to analyze patient outcome. A 26% incidence of pulmonary embolus occurred. However patients who had bilateral free-floating thrombi had a 42.8% incidence of pulmonary embolus. Receiving a 7-day course of heparin therapy with a partial thromboplastin time (PTT) at 1.5 times control was 53.2% of patients; 55.4% of the patients underwent follow-up examination, and the mean time to clot attachment was 9.2 days. Patients should receive anticoagulation for 10 days or until clot attachment. Patients with persistent, bilateral free-floating thrombi, or propagation of thrombus are candidates for potential caval interruption. Serial scans should be performed to monitor the thrombus for attachment or alteration. PMID- 2192693 TI - Organ distribution of radiolabeled enteric Escherichia coli during and after hemorrhagic shock. AB - Translocation of intestinal bacteria to the blood during hemorrhagic shock (HS) has been confirmed in rats and humans. The current study was designed to trace the path of translocated intestinal bacteria in a murine HS model. Thirty-one rats were gavaged with 1,000,000 counts of viable 14C oleic acid-labeled Escherichia coli. Forty-eight hours later the animals were bled to 30 mmHg until either 80% of their maximal shed blood was returned or 5 hours of shock had elapsed and they were resuscitated with Ringer's lactate as previously described. Control animals were cannulated but not shocked. Eight rats immediately after shock and resuscitation, 6 rats 24 hours after shock, 3 rats 48 hours after shock, and 4 animals that died in shock had their heart, lung, liver, spleen, kidney, and serum harvested, cultured, and radioactive content measured. Translocated enteric bacteria are found primarily in the lung immediately after shock with redistribution to the liver and kidney 24 hours later. Animals surviving to 48 hours were capable of eliminating the majority of the bacteria from their major organ systems. Positive cultures for E. coli were also found in the blood, lung, liver, and kidney. We speculate that the inflammatory response stimulated by the bacteria in these organs may contribute to the multiple-organ failure syndrome seen after HS. PMID- 2192695 TI - Superiority of closed suction drainage for pancreatic trauma. A randomized, prospective study. AB - During a 42-month period, 65 patients sustaining pancreatic injuries were treated. They were randomized on alternate days (two separate trauma teams) to receive sump (S) or closed suction (CS) drainage. Twenty-eight patients were randomized to S and 37 to CS; there were six early deaths, which precluded drainage analysis, leaving 24 evaluable S patients and 35 CS patients. Penetrating wounds occurred in 71% and blunt in 29%. No significant differences appeared between the groups with respect to age, Penetrating Abdominal Trauma Index (PATI), Injury Severity Score (ISS), or grade of pancreatic injury. Twelve patients in each group required resection and drainage for grade III injuries, with the remaining patients receiving external drainage alone. Five of twenty four S patients versus one of thirty-five CS patients developed intra-abdominal abscesses (p less than 0.04). We conclude that septic complications after pancreatic injury are significantly reduced by CS drainage. Bacterial contamination via sump catheters is a major source for intra-abdominal infections after pancreatic trauma. PMID- 2192697 TI - The Thirteenth Hastings lecture. My life with the National Institutes of Health Artificial Heart Program. PMID- 2192696 TI - Gastrointestinal hormone responses to meals before and after gastric bypass and vertical banded gastroplasty. AB - The purpose of the study was to examine the gastrointestinal hormone responses to meals in morbidly obese patients before and after Roux-en-Y gastric bypass (GBP; n = 9) or vertical banded gastroplasty (VBG; n = 7). On consecutive days before and after operation, we measured changes in peripheral blood levels of glucose, insulin, enteroglucagon, serotonin, vasoactive intestinal polypeptide (VIP), and cholecystokinin (CCK) in response to a standardized glucose or protein-fat meal. The percentage of excess weight lost at 6 months after operation was 66.3% +/- 4% and 41.8% +/- 5% for GBP and VBG, respectively (p less than 0.01). The 3-hour integrated glucose response to a glucose meal decreased from 145.3 +/- 33.7 to 75.8 +/- 15.7 g min/L (p less than 0.02) after GBP. This was associated with a decrease in 3-hour integrated insulin response from 22.8 +/- 8.2 to 10.5 +/- 4.9 mU min/L. Vertical banded gastroplasty patients had lesser reductions of hyperglycemia and hyperinsulinemia. Neither the CCK, serotonin, nor VIP responses to meals were altered by either operation. The 3-hour integrated enteroglucagon response to glucose increased markedly in GBP patients after operation from 11.8 +/- 6 to 133.4 +/- 38 nmol min/mL (p less than 0.02). This increase in enteroglucagon occurred at the same time as development of dumping symptoms, which occurred exclusively in GBP patients after glucose but not protein. We conclude that (1) GBP surgery for morbid obesity results in amelioration of glucose intolerance and hyperinsulinemia, (2) CCK does not mediate an endocrine satiety effect of surgery, (3) GBP is associated with an exaggerated enteroglucagon response to glucose, and (4) enteroglucagon appears to be a marker of the dumping syndrome in GBP patients. PMID- 2192698 TI - Stereotactic radiosurgery: does Australia need it? PMID- 2192699 TI - Tumour necrosis factor in surgical illness. AB - TNF is a multipurpose molecule which works alongside other cytokines to stimulate and coordinate immune and inflammatory responses to antigenic challenges. It is extremely well conserved throughout all mammal species, and obviously confers considerable survival advantage. There are circumstances, however, in which TNF itself can be a source of tissue injury. This occurs in septic shock when the magnitude of the host response is overwhelming. TNF also initiates the energy substrate mobilization required to meet the heightened fuel demands associated with immunological, inflammatory and wound-healing activities. In chronic infection and malignancy this may lead to severe depletion of host tissues with its own attendant morbidity and mortality. At present our understanding of the host response is expanding rapidly. The challenge for the future will be to manipulate this response selectively, to maximize its influence on the disease while minimizing its negative impact on the host. PMID- 2192700 TI - Ioversol in ascending phlebography--a clinical trial. AB - In this controlled randomised double-blind parallel group study of the use of ioversol-240 and ioversol-320 in venography all studies were considered diagnostic with comparable quality in the two groups. Patient tolerance was high with mild heat observed in 7 patients in the ioversol-320 group and 1 patient in the ioversol-240 group. Assessment of pain was also comparable (2 patients in the ioversol-240 group and 1 in the ioversol-320 group). Both strengths of the contrast agent produced no clinically significant, drug related, changes in vital signs or laboratory parameters and there were no significant clinical adverse reactions. PMID- 2192701 TI - Sirenomelia: prenatal sonographic features. PMID- 2192702 TI - Hydrometrocolpos: diagnosis and follow-up by ultrasound--a case report. AB - Hydrometrocolpos is accumulation of secretions in the vagina and uterus, caused by excessive intrauterine stimulation of the infant's cervical mucous glands by maternal oestrogen in the presence of an intact hymen (Wilson et al 1978). Hydrocolpos is dilatation of the vagina proximal to a congenital obstruction. If the uterus is also dilated, the condition is called hydrometrocolpos. Most cases of hydrocolpos are associated with an imperforate hymen that forms a thin bulging membrane between the labia. Though many cases of hydrometrocolpos have been reported in literature, there is no case report which shows classical ultrasound findings and follow up ultrasound scans to show the involuted uterus. We are presenting a case report whose diagnosis was established on ultrasound. This case highlights the value of ultrasound in diagnosing this condition and excluding other associated renal anomalies. PMID- 2192703 TI - [Psychotherapy using the Catathymic Picture Experience. Principles and practice of psychotherapy work using daydreams]. PMID- 2192704 TI - [Penetrating heart injury]. AB - A report was made on a 25 year old patient with a penetrating heart injury with basic diagnosis, and treatment. A successful management was a result of good performance of the resuscitation chain, exactness of the clinical diagnosis and interdisciplinary cooperation between surgeons and anaesthetists. PMID- 2192705 TI - Tumor hypersensitive DNA is enriched in c-myc sequences and reacts differentially with normal and malignant genomic DNA. AB - We now show that exposure of B16 melanoma cells to bromodeoxyuridine increases cell-substratum interactions concurrent with an increase in genome susceptibility to nucleases. Hypersensitive DNA was isolated after mild nicking of nuclei with DNase I followed by repair with DNA polymerase I in the presence of biotin-19-SS dUTP and affinity chromatography on streptavidin-agarose. Dot blot studies showed that the hypersensitive DNA is enriched in c-myc sequences compared to total tumor genomic DNA, and hybridizes preferentially to the latter, compared to normal genomic DNA, particularly when prepared from BrdU-treated cells. Since hypersensitive DNA can hybridize with multiple Alu sequences in the genome, we postulate that one of the mechanisms for its differential reactivity may be by recognition of an unequal number of Alu repeats in normal and tumor genomic DNA. PMID- 2192706 TI - The effect of amylin and calcitonin gene-related peptide on insulin-stimulated glucose transport in the diaphragm. AB - The two peptides calcitonin gene related peptide (CGRP) and amylin at 1 uM levels in an isolated rat diaphragm preparation inhibited insulin stimulated 2 deoxy[3H]glucose transport by 30 and 60 percent, respectively; this was the case at maximal (1 uM) and sub-maximal (0.5 mU) insulin concentrations. No effect was measured on the basal level of 2-deoxy[3H]glucose transport. PMID- 2192707 TI - Production of endothelin-1 by rat cultured mesangial cells. AB - We investigated whether ET-1 is synthesized by and released from mesangial cells. ET-1-like immunoreactivity (LI) released into medium increased time-dependently under a serum-free condition. The amounts of ET-1-LI released into the medium was augmented in the presence of fetal calf serum. Reverse-phase HPLC profile of the conditioned media revealed a major component coeluting with standard ET-1. Northern blot analysis of poly(A) +RNA extracted from mesangial cells showed a single major band corresponding to the size of preproET-1 mRNA (2.3 kb). These findings demonstrate that ET-1 is synthesized by and released from rat mesangial cells and suggest a possibility that it acts on their own cells as an autocrine factor. PMID- 2192708 TI - Application of automated image analysis to demonstrate the correlation between ras p21 expression and severity of gliomas. AB - We found a direct correlation between increasing ras p21 protein immunopositivity and severity of human glioma using computer-assisted, digital-image processing to quantify the amount of p21 immunoreactive to the monoclonal antibody RAP-5. We determined that there was a significant difference in reactivity between glioblastoma multiformes and more-differentiated astrocytomas (experiment-wise error less than 0.05). This result confirmed the conclusions made on the same tumors using standard light microscopy and visual examination. Immunohistochemistry quantized by automated image analysis may be a useful adjunct to current histopathological strategies since it decreases assay subjectivity and variation. PMID- 2192710 TI - Amino acid sequence from degu islet amyloid-derived insulin shows unique sequence characteristics. AB - The main protein of enriched and purified amyloid from Octodon degus pancreatic islets was identified as insulin. The material was reduced and alkylated and the A- and the B-chain were separated by reversed phase chromatography and subjected to Edman degradation and amino acid analysis. It was shown that the A-chain contains two additional C-terminal amino acid residues (i.e. a total of 23 residues) and that the B-chain has a deletion in the C-terminal part (i.e. a total of 29 residues). The obtained sequence follows: A-chain: GIVDQCCNNICTFNQLQNYCNVP B-chain: YSSQHLCGSNLVEALYMTCGRSGFYRPHD. PMID- 2192709 TI - Canine IAPP cDNA sequence provides important clues regarding diabetogenesis and amyloidogenesis in type 2 diabetes. AB - Islet amyloid polypeptide (IAPP) is a recently discovered pancreatic islet hormone which is stored with insulin in beta cell granules. IAPP may have a significant role in the development of Type 2 diabetes mellitus due to its propensity to form islet cell-disrupting amyloid deposits, and by opposing the action of insulin in peripheral tissues. Most evidence to-date suggests that an intrinsic structural motif of IAPP is linked to the amyloidogenicity of IAPP, and that this motif occurs only in those species (e.g., humans and cats) that also develop age-associated or Type 2 diabetes We utilized polymerase chain reaction methodology in this study to obtain the IAPP nucleotide and protein sequences of the dog, a species not known to develop islet amyloid. We show that dog IAPP contains the same putative amyloidogenic sequence (GAILS) at residues 24-28 as human and cat IAPP, and that although dogs do not develop islet amyloid they do develop IAPP-derived amyloid in association with neoplastic beta cells (i.e., insulinomas). These results provide strong evidence that the amyloidogenicity of IAPP is linked to at least two prerequisites: a species-specific amyloidogenic structural motif, and aberrations in the synthesis (or processing) of IAPP which leads to increased concentration of IAPP in the local milieau. PMID- 2192711 TI - Production of granulocyte/macrophage colony-stimulating factor by cultured astrocytes. AB - We investigated the production of interleukin-3 (IL-3)-like factor by murine astrocytes. Supernatants from lipopolysaccharide (LPS)-stimulated astrocytes induced proliferation of IC-2, an IL-3- and granulocyte/macrophage colony stimulating factor (GM-CSF)-dependent cell line. This activity was completely neutralized by the antibody against GM-CSF but not by the anti-IL-3 monoclonal antibody. Northern blot analysis revealed the expression of GM-CSF mRNA, but not of IL-3 mRNA, in cultured astrocytes. These results indicate that with proper stimuli murine astrocytes produce GM-CSF. PMID- 2192712 TI - Endothelin-3 concentrations in human plasma: the increased concentrations in patients undergoing haemodialysis. AB - Plasma immunoreactive endothelin-3 (ir-ET-3) concentrations were measured by a sandwich-enzyme immunoassay (sandwich-EIA) for endothelin-3 (ET-3). The assay method consists of two antibodies directed against N-terminal and C-terminal portions of ET-3. It detects as little as 0.1 pg/well of ET-3 without the crossreaction with endothelin-1, endothelin-2 and big ET-3. Plasma ir-ET-3 concentrations were found to be 0.45 +/- 0.07 pg/ml (mean +/- SD) in healthy volunteers, and were increased in patients undergoing haemodialysis (0.83 +/- 0.26 pg/ml, p less than 0.001). In reverse-phase HPLC, ir-ET-3 in normal plasma and in plasma of haemodialysis patients was eluted at the position of authentic ET-3, indicating that ir-ET-3 in plasma detected by the EIA was ET-3 itself. These results suggest that circulating ET-3 exists in normal human plasma and that production and/or metabolism of ET-3 may be altered in patients undergoing haemodialysis. PMID- 2192713 TI - [Synthesis of immunoglobulin conjugates with dehydrogenases]. AB - Three methods of synthesis of immunoglobulin conjugates with malate, lactate and glucose-6-phosphate dehydrogenases, involving the sodium metaperiodate oxidation of immunoglobulin carbohydrate component, use of water-soluble carbodiimide and the one-step glutaraldehyde technique, were compared. The glutaraldehyde method was shown to give immunoglobulin-dehydrogenase conjugates with high catalytic and immunochemical activity, which may be useful for enzyme-immunoassay. PMID- 2192714 TI - [Molecular nature of oncogene HRAS1 damage in human breast carcinoma: G----T transversion in codon 12 of one allele during deletion of other allele]. PMID- 2192715 TI - Effects of pioglitazone on hepatic and peripheral insulin resistance in Wistar fatty rats. AB - Effects of pioglitazone (5-[4-[2-(5-etyl-2-pyridyl)ethoxy] benzyl]-2,4 thiazolidinedione, AD-4833, also known as U-72, 107E) on peripheral and hepatic insulin resistance were examined using genetically obese-hyperglycemic rats, Wistar fatty. Pioglitazone was administered to fatty rats (3 mg/kg/d) and lean rats (10 mg/kg/d) for 6 days. Pioglitazone decreased hyperglycemia and hypertriglyceridemia without affecting hyperinsulinemia in the fatty rats, and significantly reduced plasma levels of triglyceride and insulin without altering normoglycemia in the lean rats. The same rats were subjected to an isotopic method combined with a euglycemic clamp technique for assessing insulin sensitivity in hepatic glucose production (HGP) and peripheral glucose utilization (PGU). HGP decreased and PGU increased in response to infused insulin in the lean rats but did not in the fatty rats, indicating that insulin resistance was present in the liver and peripheral tissues of the fatty rats. Treatment with pioglitazone restored the responses of HGP and PGU to infused insulin in the fatty rats, but did not produce any changes in the lean rats. When the same levels of glycemia and insulinemia were established by 480 mU/h of insulin in both treated and control fatty groups, PGU was 1.5-fold higher and HGP was 3-fold lower in the pioglitazone treated group. Pioglitazone also corrected the abnormality in hepatic enzyme regulation by insulin of the fatty rats: glucose-6-phosphatase decreased and glucokinase increased, suggesting the increased response of the liver to insulin and the resultant suppression of HGP. Therefore, pioglitazone is expected to be useful for treating abnormal glucose and lipid metabolism in non-insulin-dependent diabetes mellitus through reducing insulin resistance of the peripheral tissues and liver. PMID- 2192716 TI - [Antisecretory effect of the H2-histamine receptor antagonist ranitidine in water soluble tablets and film-coated tablets. Results of a randomized, placebo controlled crossover study in humans]. AB - This clinico-pharmacological trial aimed to prove equivalence between the known film-coated tablets of ranitidine (Sostril Filmtabletten) and the novel dispersible tablets for the preparation of a drinkable solution (Sostril Aquatabs) on a pharmacodynamic level. Therefore, the influence of single oral doses of the two ranitidine preparations (2 X 150 mg p.e.m. each) and placebo on the gastric hydrogen ion concentration was studied in 12 healthy volunteers using a randomized cross-over design. pH-values of the gastric juice were measured and recorded continuously for 24 h. Median pH-values for the entire study period were 2.20, 2.15 and 1.40 for dispersible tablets, filmcoated tablets and placebo, respectively. During the night-time median pH-values of 3.45 for both ranitidine preparations and 1.40 for placebo were calculated. From these results it can be concluded that the novel dispersible tablets are equivalent to the ranitidine filmcoated tablets with regard to their pharmacodynamic potency. PMID- 2192717 TI - Efficacy of a combined bezafibrate retard-colestyramine treatment in patients with hypercholesterolemia. AB - In a placebo-controlled randomized study the effect of combined bezafibrate colestyramine therapy in comparison with monotherapy with both drugs was investigated. 47 patients with primary hypercholesterolemia received 400 mg bezafibrate (Cedur) retard/d, subsequently bezafibrate retard plus colestyramine (24 g/d) or colestyramine plus placebo in a double-blind fashion. The combination therapy was most effective (LDL decrease 36%, HDL-C increase 31%, apoprotein B decrease 28%), bezafibrate and colestyramine were equally effective with regard to LDL-C and apoprotein B, but only bezafibrate decreased triglycerides (-37%) and increased HDL-C (+24%). Bezafibrate was well-tolerated, but gastro-intestinal side-effects were frequent during therapy with colestyramine, and 16 patients tolerated only a reduced dosage of this drug. From the results presented it can be concluded that combined therapy with bezafibrate retard plus colestyramine is highly effective in the treatment of severe hypercholesterolemia. PMID- 2192719 TI - The 'Cambridge' stereotactic biopsy instrument. AB - The recent expansion in CT guided stereotactic biopsy has revealed deficiencies in biopsy instrumentation. In view of this, the authors have developed a versatile side-cutting cannula which has been used successfully in over eighty stereotactic biopsies as well as for the drainage of deep seated abscesses. PMID- 2192718 TI - Walther Birkmayer--a tribute on his 80th birthday. PMID- 2192720 TI - Vertigo caused by scalenus anterior compression of the subclavian artery: a report of two cases. AB - Two cases of vertigo with subclavian artery stenosis are presented. In both cases, the angiograms revealed left subclavian artery stenosis at the middle portion of the clavicle as well as kinked origin of the vertebral artery. After resection of the anterior scalene muscle, the stenosis and the vertigo resolved. PMID- 2192721 TI - Diabetes in the elderly. PMID- 2192722 TI - Renal system complications in HIV infection. AB - This article has provided an overview of the effects of HIV on renal function. Most transmission of the virus occurs by sexual, blood, and perinatal contact. CD 4 positive cells, especially those that are integral components of the immune system, serve as the reservoir for the reproduction of the virus. The resulting effect is destruction of the immune system with eventual multisystem failure and death. Renal complications arise from several factors, notably the compounding effects of chronic dehydration, malnutrition, infection, and use of nephrotic agents. Acute renal complication can be reversible with prompt assessment, and management directed at maintaining hydration, preventing sepsis, and carefully monitoring drugs. A chronic, irreversible renal disease in HIV is due, in large part, to a syndrome known as AIDS nephropathy, characterized by glomerular sclerosis and nephrotic-type symptoms, which ultimately lead to the need for dialysis. Aids nephropathy is seen most often in intravenous drug users, Haitians, and blacks with HIV. End-stage disease complicates the course of HIV and contributes to early mortality. A small, but significant number of renal patients acquires HIV infection as a result of multiple blood transfusions or through organ donation. Concentrated exposure to blood and body fluid during dialysis necessitates implementation of meticulous infection control procedures to protect both staff and patients. Guidelines by the CDC suggest that universal precautions adequate to prevent the spread of hepatitis B will suffice for HIV as well. HIV infection presents special challenges for those involved with renal management. Prevention and management of renal complication are made possible by thorough understanding of the complex network and interaction of the disease process. PMID- 2192723 TI - Pathophysiology of shock. AB - Shock is an acute widespread reduction in effective tissue perfusion that invokes an imbalance of oxygen supply and demand, anaerobic metabolism, lactic acidosis, cellular and organ dysfunction, metabolic abnormalities, and, if prolonged, irreversible damage and death. The pathophysiologic events in the various types of shock are different and complex with hemodynamic and oxygenation changes, alterations in the composition of the fluid compartments, and various mediators. Shock results from a change in one or a combination of the following: intravascular volume, myocardial function, systemic vascular resistance, or distribution of blood flow. The clinical types of shock include hypovolemic, cardiogenic, distributive (septic), and obstructive. An understanding of the pathophysiologic changes, rapid diagnosis, appropriate monitoring, and appropriate therapy can reduce the high morbidity and mortality in shock states. PMID- 2192724 TI - Cellular and humoral mediators of sepsis syndrome. AB - The story of mediators in sepsis syndrome is developing extremely rapidly and continues to unfold. This discussion has focused on those areas most studied and those that have the greatest clinical implications in the context of current knowledge. There are a number of mediators under active investigation that have not been reviewed here because their discussion is beyond the scope of this article. Just how all the pieces of the intricate cascade of events ultimately fit together is yet to be seen. However, the availability of important probes, such as cyclooxygenase inhibitors, TNF, anti-TNF, IL1, anti-IL1, anti-proteases, antioxidants, and antiendotoxin, is allowing major progress to be made in a short period of time. Transferring this knowledge to the bedside and everyday clinical practice is a slower process, but the prospects are bright for innovative new therapies for sepsis syndrome, septic shock, and the multiple organ failure associated with these clinical entities. PMID- 2192725 TI - Vasoactive drug therapy in shock. AB - The process of supporting the patient in shock with vasoactive infusions is never a static one. There are a variety of vasoactive infusions available; unfortunately, no one medication effectively corrects the numerous abnormalities in all forms of shock and no magic formula exists for combining medications to achieve optimum tissue perfusion. The nurse is challenged to utilize keen assessment skills and sophisticated monitoring techniques to follow the patient's response to changing vasoactive drug therapy. The nurse must collaborate with the physician and other health team members to integrate drug therapy with the other aspects of shock therapy, including fluid repletion, oxygenation and ventilation, metabolic support, and antibiotic therapy to facilitate the successful resuscitation of the patient in shock. PMID- 2192726 TI - Antibiotic therapy in septic shock. AB - Septic shock is a life-threatening illness characterized by hypotension, impaired organ function and/or failure, and metabolic abnormalities. Septic shock can develop in patients infected with a variety of gram-positive and gram-negative bacteria, viruses, fungi, rickettsiae, spirochetes, protozoa, and parasites. Immediate recognition, diagnosis, and treatment are key elements in reducing the morbidity and mortality associated with this condition. Rapid administration of appropriate antibiotics in correct doses plays a major role in patient survival. Infections with gram-negative bacteria appear to be associated with septic shock more than any other etiologic agent; therefore, antibiotic selection must include those drugs with superior gram-negative coverage. The selection of appropriate antibiotics should be based on sound clinical judgement plus knowledge of the antimicrobials used. The principles of rational therapy include the following: (1) know the type of microorganisms or suspected organism being treated; (2) be familiar with resistant organisms in both the community as well as the hospital; and (3) initiate combination therapy with a beta-lactam antibiotic plus an aminoglycoside or use monotherapy with either a carbapenem or selected third generation cephalosporin. After culture results are known, the antibiotic regimen should be narrowed to cover the specific infecting microorganism using the least expensive, least toxic antibiotic available. The beta-lactam antibiotics include all penicillins, cephalosporins, carbapenems, and monobactams. Penicillins with extensive gram-negative coverage include all the carboxy (carbenicillin, ticarcillin, and ticarcillin plus clavulanic acid) and ureido (piperacillin, mezlocillin, azlocillin) penicillins. The third generation cephalosporins (cefoperazone, cefotaxime, ceftazidime, ceftizoxime, ceftriaxone, and moxalactam) have the broadest gram-negative coverage within the cephalosporin family.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2192727 TI - Renal response to shock. AB - When the MAP decreases below approximately 75 mm Hg, renal autoregulatory processes are no longer effective. Decreased renal blood flow often leads to ATN and its related uremic syndrome. The patient with ATN typically experiences four successive phases as the ATN progresses and then eventually resolves. During the oliguricanuric phase of ATN, multiple organ systems and physiologic processes are affected by the alterations occurring as the result of severely altered renal function. With appropriate treatment, such as fluid-electrolyte and acid-base control, nutritional support, and renal replacement therapy, a return to normal renal function is often possible. PMID- 2192728 TI - Adult respiratory distress syndrome. A complication of shock. AB - ARDS is a complex type of respiratory failure that usually is a complication of a catastrophic critical illness, such as shock. Mortality is high, especially in patients with septic shock and multisystem failure. Mortality often is related to complications of refractory hypoxemia. Identifying patients at risk for developing ARDS and early recognition of ARDS are important so that treatment can be initiated to prevent the potentially lethal consequences of refractory hypoxemia. The nurse has an important role in collaborating with the physician and respiratory therapist to support the patient's oxygenation, ventilation, and tissue oxygen delivery system. The nurse is responsible for performing highly sophisticated assessment of clinical and hemodynamic parameters to evaluate the effectiveness of therapy. A key role of the nurse is anticipating, recognizing, and reporting to the physician complications of hypoxemia and complications of therapy that can lead to sepsis, airway trauma, or failure of other organ systems. PMID- 2192729 TI - Disseminated intravascular coagulation and shock. Multisystem crisis in the critically ill. AB - Acute primary conditions can produce pathophysiologic alterations in the normal coagulation mechanism to promote the simultaneous hemorrhagic and thrombotic events of DIC with the resultant development of shock. Additionally, as shock progresses, it can cause alterations in the hemostatic mechanism to produce DIC. The appearance of DIC in shock and shock in DIC are potentially life-threatening conditions in the critically ill. Medical management can include anticoagulant therapy, such as heparin, and replacement of clotting factors and platelets. The intensive, knowledgeable nursing management of the patient includes physiological and psychological support and can be vital to minimize the mortality and morbidity associated with DIC and shock. PMID- 2192730 TI - Gastrointestinal complications in shock. AB - The gut organs are vulnerable to injury during shock because of ischemia and reperfusion of the microcirculation. These injuries result in upper GI hemorrhage, liver dysfunction, and pancreatic and mesenteric necrosis. Toxic mediators, released via lymph drainage and with reperfusion, contribute to the failure of other organs and the development of refractory shock. Until single organ perfusion can be measured, the primary goal of care is to maintain systemic perfusion. Secondary goals are to decrease hydrogen ion accumulation, minimize pancreatic stimulation, remove hepatotoxic agents, and reduce blood bacteria. Gut ischemia is simply one piece of the puzzle in the multiple organ response to reduced systemic oxygenation and perfusion that characterizes the clinical syndrome of shock. PMID- 2192732 TI - Shock in the pediatric patient. AB - Care of the child in shock requires careful and constant assessment of the child's systemic perfusion. In addition, oxygenation and ventilation must be supported. The child's heart rate must be maintained, since pediatric cardiac output often is directly related to heart rate. The goal of treatment of shock of any origin is to ensure that cardiac output is adequate to provide tissue oxygenation and substrate delivery. This goal is accomplished through careful titration of intravenous fluids to optimize ventricular preload and maximization of ventricular function (often with inotropic or vasodilator support). The child should be kept warm, and careful regulation and evaluation of total fluid intake and output is necessary. Parents should be allowed to remain with the child as much as possible, since this will comfort both the child and the parents. The child should be prepared gently for any painful procedures, and realistic but compassionate communication with the entire family is essential. Through constant assessment and evaluation of patient response to therapy, the nurse is in the best position to detect early signs of compromise and to determine effectiveness of therapy. Therefore, it is imperative that the nurse possess a thorough understanding of the pathophysiology and clinical progression of shock in the child, as well as the rationale and potential complications of management. PMID- 2192731 TI - Preventing septic shock. Infection control in the intensive care unit. AB - Preventing nosocomial infection in the critically ill patient is a challenge for the critical care nurse. The prevention of nosocomial infection may be impossible in the critically ill patient as long as invasive therapeutic interventions are key to patient care. Therefore, nursing practice must be guided by a clear understanding of the patient's host defense mechanisms and how they are jeopardized by the underlying medical condition and therapeutic interventions. Classic recommendations of infection control practices, such as hand washing and meticulous aseptic technique, plus an awareness of the many ways that microorganisms can contaminate and inoculate the patient are essential for preventative nursing care. The most effective infection control measures may be continual patient assessment, observing for subtle changes that indicate an infection is incubating. It is the early distinction of infection as the underlying mechanism for fever, inflammatory response, and clinical deterioration that can best facilitate an expedient and appropriate course of therapy and minimize the consequences of disease. PMID- 2192733 TI - The syndrome of multiple organ failure. AB - Current technology has prolonged the life support of patients with organ failures. The onset of MOF follows an inciting event and develops a clinical pattern of lung, liver, and kidney failure. Laboratory evidence of the syndrome includes hyperbilirubinemia, hyperglycemia, increased blood lactate, and reduced levels of hepatic proteins. Energy expenditure in MOF is increased and severe sepsis or septic shock can initiate the process of hypermetabolism and MOF. Current therapy is aimed at source control, restoration of oxygen transport, and metabolic support. Critical care nursing provides a technological and humanistic approach in developing a supportive environment for patients and families. Scientific study of the effects of nursing interventions on patient outcomes is needed to evaluate critical care nursing activities. PMID- 2192734 TI - The neuroendocrine approach to psychiatric disorders: a critical appraisal. AB - Tremendous efforts have been made to exploit the strategy of measuring the secretion of hormones into the plasma by the pituitary as a "window to the brain" and therefore as an insight into potential neurotransmitter receptor lesions in patients with psychiatric disorders. This contribution focuses upon the advantages and drawbacks of the neuroendocrine approach, caution and objectiveness necessary for the critical evaluation and interpretations of the data. Factors related to the neurobiology of the medial basal hypothalamus and its peculiar features, the information that can be derived from the administration of a specific neuroregulatory hormone or a neuroactive compound and evaluation of the evoked hormone release, the multiple constraints related to the drug itself and/or the physiology or coexisting pathology of the psychiatric patient under examination, are thoroughly discussed. PMID- 2192735 TI - Heat-shock proteins in autoimmune arthritis: a critical contribution based on the adjuvant arthritis model. AB - Recognition of self protein epitopes, apart from those engaged in idiotypic network interactions and MHC restriction, is probably a physiological event in the normal functioning immune system. Furthermore T and B cells recognizing self antigens can be easily cloned from healthy individuals and sometimes be shown to confer autoimmune disease by passive transfer in the experimental situation. The issue is how potentially autoaggressive cells can become activated and how such activity can be contained safely. Experimentally, autoimmune disease can be evoked by immunization with autoantigens (encephalomyelitis, thyroiditis etc.) or with foreign antigens that feature antigenic relationships with self antigens (adjuvant arthritis). In both situations transfer of disease has been shown with cloned T cells of a single specificity. In addition, specific control of disease using the same cloned T cells has been achieved. Adjuvant arthritis has been illustrative in these respects. By means of specificity analysis of cloned T cells, a 65 kD heat shock protein of mycobacteria was identified as crucial in the disease. Immunization with this antigen has been found to prevent the development of disease, including forms elicited without mycobacterial involvement. Furthermore, vigorous immunological responses to HSP65 were found both in experimental animals and also in humans as a consequence of exposition to various infectious organisms. By their conserved nature HSPs have ample potential for dangerous mimicry. Recent evidence accumulated suggesting that the same HPS65 may be crucial in human chronic arthritis as well. Therefore it is hoped that extrapolation of the experimental findings to the human situation will help the development of specific means, either T cells or antigens, to control spontaneous autoimmune arthritis in man. PMID- 2192736 TI - Rapid diagnostic techniques: how to get the most from your microbiology laboratory. PMID- 2192737 TI - Advances in the management of diabetes mellitus. AB - This article shall highlight several areas where recent developments have made, and may make in the future, practical advances to diabetes care. These advances have been in the areas of insulin therapy, glucose monitoring, identifying pre diabetics and using immunosuppressive agents in pre-diabetes and early diabetes, pancreatic transplantation, and managing acute and chronic complications of diabetes. PMID- 2192738 TI - The application of enhanced chemiluminescence to membrane-based nucleic acid detection. AB - The ECL gene detection system is a novel, sensitive, non-radioactive system for the detection of nucleic acid hybridized on both nylon and nitrocellulose membranes. It is characterized by direct labeling of probe sequences with horseradish peroxidase combined with an enhanced chemiluminescent (ECL) detection reaction; the light output is captured on blue-light sensitive film. The application of the system to a range of standard molecular biology hybridization techniques is described. PMID- 2192739 TI - The pUC18CM plasmids: a chloramphenicol resistance gene cassette for site directed insertion and deletion mutagenesis in Escherichia coli. PMID- 2192740 TI - Preparation of digoxigenin-labeled probes by the polymerase chain reaction. PMID- 2192741 TI - An overview of computer algorithms for deconvolution-based assessment of in vivo neuroendocrine secretory events. AB - The availability of increasingly efficient computational systems has made feasible the otherwise burdensome analysis of complex neurobiological data, such as in vivo neuroendocrine glandular secretory activity. Neuroendocrine data sets are typically sparse, noisy and generated by combined processes (such as secretion and metabolic clearance) operating simultaneously over both short and long time spans. The concept of a convolution integral to describe the impact of two or more processes acting jointly has offered an informative mathematical construct with which to dissect (deconvolve) specific quantitative features of in vivo neuroendocrine phenomena. Appropriate computer-based deconvolution algorithms are capable of solving families of 100-300 simultaneous integral equations for a large number of secretion and/or clearance parameters of interest. For example, one application of computer technology allows investigators to deconvolve the number, amplitude and duration of statistically significant underlying secretory episodes of algebraically specifiable waveform and simultaneously estimate subject- and condition-specific neurohormone metabolic clearance rates using all observed data and their experimental variances considered simultaneously. Here, we will provide a definition of selected deconvolution techniques, review their conceptual basis, illustrate their applicability to biological data and discuss new perspectives in the arena of computer-based deconvolution methodologies for evaluating complex biological events. PMID- 2192743 TI - PaperChase: a user-friendly program for searching the biomedical literature. AB - PaperChase is a computer program which provides an efficient interface to the National Library of Medicine's MEDLINE database of references to the biomedical literature. The database includes references (citations) and abstracts compiled from Index Medicus, the International Nursing Index and the Index to Dental Literature. PaperChase may be accessed using any computer terminal or personal computer with modem. No special knowledge of computers or biomedical terms is necessary. Simple menus enable the novice to search the biomedical literature without training. A command language speeds searching for the experienced user. PaperChase does not require the user to know the database's indexing terminology, called Medical Subject Headings. Everyday language may be used and PaperChase will translate, or "map", the user's search term into the required Medical Subject Heading. PaperChase monitors a search in progress and suggests additional Medical Subject Headings which can be used to broaden or narrow a search. The searcher can order a full-text photocopy of any reference found in PaperChase. Support documentation and a subscriber newsletter are provided at no charge. Trained search specialists are available to offer assistance and to answer questions. PMID- 2192742 TI - The development of computer simulations of the geometries and thermodynamics of biological molecules. AB - The historical development of computer simulations of molecular geometry and thermodynamics (molecular mechanics, force field method) is outlined. The advantages and disadvantages of techniques such as energy minimization, molecular dynamics and free energy perturbation are discussed. An example is included that shows how energy minimization studies of dopamine D-2 antagonists have been used to develop an understanding of the three-dimensional pharmacophore necessary for this pharmacological activity. PMID- 2192744 TI - Bronchial brushing and biopsy: a comparative evaluation in diagnosing visible bronchial lesions. AB - One hundred and forty patients underwent 142 brushings and conventional biopsies of suspected malignant lesions of the lung through a fibreoptic bronchoscope. Both samples were taken from the same area. One hundred and three patients showed positive results on brushing and 90 on biopsy. Thirty-nine diagnoses were negative on brushing and 52 on biopsy. A correct cell typing was obtained in 105 of 109 diagnoses of malignancy. Final diagnoses showed 118 malignant lesions and 22 benign conditions. False positives were respectively, 2 on brushing and 1 on biopsy, while false negatives were 17 on brushing and 30 on biopsy. Brushing showed higher sensitivity (85.5%) and accuracy (86.6%) than biopsy. A combination of the two techniques gives an accuracy rate of 94.3%. PMID- 2192745 TI - Quantitative aspects of the mucosal immunity and bacteriology of the nasopharynx and middle ear cavity. Studies on children with clinically different forms of otitis media. PMID- 2192746 TI - [Mitral valve prosthesis with preservation of the chordae and papillary muscles in patients with mitral insufficiency]. AB - Mitral valve (MV) prosthetics was performed in 14 patients in its insufficiency. In MV replacement the chordopapillary apparatus (CPA) of the posterior cusp was left intact. The EMIKS or LIKS disk prosthesis was implanted in most cases (6 and 6 patients, respectively), the biological BAKS prosthesis was implanted in 2 patient. Orientation of the large semicircumference in the direction of the anterior or posterior commissure was the optimal orientation for the disk prostheses. Measurement of the parameters of hemodynamics on the operating table showed that reduction of the rigidity of the left-ventricular myocardium and the increase of the stroke index in patients with an intact chordopapillary apparatus of the posterior cusp differed significantly from those in patients with completely excised MV. Preservation of the CPA during MV replacement in patients with mitral insufficiency leads to reduction of the rigidity of the left ventricular myocardium and improvement of its function immediately on the operating table. PMID- 2192747 TI - [Isolation of the bronchi with intraoperative packing in children with bronchiectasis]. AB - The authors discuss experience in 168 operations for extirpation and segmental resection of affected bronchi in children with bronchiectases. To prevent recanalization of the bronchus after its segmental resection and to prevent the formation of an abscess in the isolated part of the lung they suggest a method for intraoperative packing of the remaining bronchi with biopolymer material. PMID- 2192748 TI - [Experience in the surgical treatment of chronic suppurative lung disease in children]. AB - Operations were performed on 750 children with cystic hypoplasia and dysontogenetic and acquired bronchiectases. The operation volume: pulmonectomy, lobectomy, combined resections, resection of pulmonary tissue with extirpation of bronchi, extirpation of bronchi. COMPLICATIONS: atelectasis, pneumonia, intrapleural hemorrhage were encountered in 87 (11.6%) children. Six (0.8%) children died. Recurrent or residual bronchiectases were found in 27 children, 18 underwent a second operation. Recurrences were encountered mainly in children with dysontogenetic bronchiectases. PMID- 2192749 TI - [Subacute subdural hematoma--report of 4 cases and a review of the literature]. AB - Subdural hematoma is divided roughly into two types acute and chronic. The two show an entirely different mode of illness. The authors have encountered 4 cases of subacute subdural hematoma in which characteristics of both types coexisted. These cases are characterized by the following. 1) The disease develops in the elderly persons with a history of trauma unknown or after minor head injury. 2) There is a relatively long period of clear consciousness and they visit a hospital when they are in the subacute stage, 3) They have a history of drinking alcohol heavily as a habit and there is a high risk of hypertension and diabetes. 4) Brain CT findings sometimes reveals mixed density hematoma. 5) Hemorrhage from the cortical artery is occasionally noted as the operative findings. Hematoma membrane is absent. 6) The outcome is generally poor because of systemic complications. As described above subacute subdural hematoma was similar to chronic subdural hematoma in the clinical course and CT findings. But operative findings of this disease indicated acute subdural hematoma. Repeated minor hemorrhage, related to coagulation disorder and brain atrophy would be important as the mechanism of subacute subdural hematoma. The effectiveness of perforation craniotomy as radical operation was low and removal of hematoma by major craniotomy was needed. The concept of subacute subdural hematoma is considered important in deciding on a therapeutic policy. PMID- 2192750 TI - Effects of prostaglandin E2 on production of new cancellous bone in the axial skeleton of ovariectomized rats. AB - The effects of prostaglandin E2 (PGE2) were histomorphometrically evaluated in cancellous bone of the axial skeleton of ovariectomized, osteopenic rats. Four months following bilateral ovariectomy (OVX) and sham-ovariectomy (SHAM) at 3 months of age, rats received daily subcutaneous injections of PGE2 at 0, 0.3, 1.0, 3.0 and 6.0 mg/kg/day for 30 days. The undecalcified fourth lumbar vertebral bodies (LVB) were processed for static and dynamic bone histomorphometry. The OVX rats possessed a slightly osteopenic LVB (17% vs. 24% cancellous bone mass). In rats given PGE2 at 3 and 6 mg/kg/day for 30 days, bone turnover, lamellar bone mass, and formation of new woven bone trabeculae were increased. Observations supported the conclusion that PGE2 activates bone modeling and remodeling, and shifts bone balance in favor of formation. In OVX rats given 6 mg PGE2/kg/day, cancellous bone mass and trabecular numbers were restored to levels found in untreated SHAM rats. Cancellous bone mass in the LVB of SHAM rats given 3 and 6 mg PGE2/kg/day increased by 16% and 30% over that of control rats. In addition, PGE2 stimulated longitudinal bone growth in both OVX and SHAM rats, a response that differed from male rats. PMID- 2192751 TI - Primary hyperparathyroidism: changes in trabecular bone remodeling following surgical treatment--evaluated by histomorphometric methods. AB - Iliac bone biopsies from 11 patients who underwent successful surgery for primary hyperparathyroidism were examined before and median 7 months after surgical treatment. Trabecular bone volume increased (p less than 0.05) and eroded (p less than 0.005) and osteoid covered surfaces decreased (p less than 0.005) in the postoperative period. Also, a decline in tetracycline labeled surfaces was noticed (p less than 0.02). Osteoid thickness, mineral appositional rate and mineralization lag time were unchanged. Bone formation rate at the level of the basic multicellular unit (BMU) was unaffected, but at the tissue level bone formation rate diminished (p less than 0.02). The surgical cure of primary hyperparathyroidism was found accompanied by a change in bone metabolism as the trabecular bone remodeling decreased from a high turnover to a low turnover state. The spongy bone mass increased after parathyroidectomy but the clinical significance of this finding was not clear. PMID- 2192752 TI - Research on diagnostic reasoning in nursing. AB - NANDA has traditionally complemented its work on the development and clinical testing of nursing diagnoses with concurrent interest in nurses' diagnostic reasoning processes. This literature review describes studies in diagnostic reasoning, including research based on the information processing model, research examining the role of intuition, and research using grounded theory to study the diagnosis of specific patient conditions. The review presents a synthesis of the research to date, and common themes in these diverse studies are identified. This review emphasizes research in nursing, although pertinent findings from cognitive psychology and medicine are included. Suggestions for future work in diagnostic reasoning are offered. PMID- 2192753 TI - Hemodynamic clinical profiles. AB - Hemodynamic profiling provides valuable information about cardiac output and its determinants: preload, afterload, and contractility. The direct and derived parameters of these determinants are used by expert critical care nurses in collaboration with medical directives for intervention to enhance clinical assessment, decisionmaking, and evaluation. This article reviews the basic and advanced aspects of hemodynamic profiling. The parameters that must be included in a complete hemodynamic profile are discussed with emphasis on the importance of index values. An algorithm is included as a guideline for use of the hemodynamic profile. A variety of clinical examples are discussed to illustrate the importance of hemodynamic profiling as an adjunct to expert critical care nursing practice. PMID- 2192754 TI - Update on ventricular assist devices. AB - Ventricular assist devices serve as a valuable adjunct to therapy in the setting of profound heart failure. The two largest patient groups--postcardiotomy and those being bridged to transplant--show an average 40-50% survival rate after ventricular assist. Several devices exist including centrifugal, pneumatic, and electrical pumps. Options for ventricular assist include right (RVAD), left (LVAD), and biventricular (BiVAD) support. Knowledge regarding the devices and the pathophysiology of severe heart failure is crucial for the critical care nurse caring for these patients. Critical care nursing interventions for bleeding, renal failure, infection, and other complications will be outlined. PMID- 2192755 TI - Using inotropic and vasodilating agents in pediatric patients with cardiac disease. AB - Inotropic and vasodilating agents are traditionally used with diuretics to manage heart failure in children with congenital heart disease. This article reviews the developmental aspects of cardiovascular physiology and the rational use of therapeutic agents for acutely ill surgical and medical pediatric patients with cardiac disease. By understanding the actions and indications for inotropic support and afterload reduction, the critical care nurse can intelligently administer these agents and evaluate their effects. PMID- 2192756 TI - Advances in the treatment of dilated cardiomyopathy. AB - The nursing care of the patient with dilated cardiomyopathy focuses on (1) improving right and left heart function, i.e., titrating vasoactive drugs to maintain acceptable cardiac index with minimum side effects (and/or monitoring the operation of a left ventricular assist device when left heart function is refractory to vasoactive drugs), (2) reducing cardiac filling pressures with diuretics, vasodilators, and/or restriction of dietary sodium, oral and IV fluids, (3) maintaining optimum oxygenation, (4) preventing complications associated with either the disease or treatment, and (5) assisting the patient/family to maintain hope during the often lengthy and crisis-filled wait for a donor heart. The critical care nurse is challenged, often for weeks or months at a time, by the complexity of this patient's physical and emotional needs and functions in a collaborative role with the entire health team in an attempt to maintain both cardiovascular and psychological stability until a donor heart is available. PMID- 2192757 TI - The child following the Fontan procedure: nursing strategies. AB - The underlying principle of the Fontan procedure, perfusing the lungs without benefit of a ventricular pump, has been reinforced by its successful application in many children with complex cardiac anomalies involving only one functional ventricle. Several different techniques that direct systemic venous return through the right atrium directly to the pulmonary arteries can be used. By separating the pulmonary and systemic circulations, reducing ventricular volume overload, and relieving cyanosis, improved cardiac function and hemodynamics can be achieved. This article reviews the surgical techniques, perioperative nursing care with particular attention to the assessment, and management of systemic venous hypertension and the long-term outlook for these children. The collaboration of physicians and critical care nurses in the postoperative care of these children and their families is vital to a successful outcome. PMID- 2192759 TI - Techniques in cardiac care: lasers, stents, and atherectomy devices. AB - Various new technologies are currently being investigated to treat cardiovascular disease less invasively than with conventional open heart surgery. Although lasers have been used in other health disciplines, their use in the cardiovascular field is relatively new. Even newer is the use of atherectomy devices and endovascular stents. It is important for the critical care nurse to be knowledgeable concerning these techniques in order to provide optimal patient care. PMID- 2192758 TI - Retrograde coronary sinus perfusion: a new approach to cardioplegia delivery. AB - Retrograde coronary sinus perfusion is a technique being used to deliver cardioplegia during cardiac surgery. This article reviews the history behind its use, the procedure for delivery, and the advantages and limitations that exist in comparison with the standard antegrade infusion of cardioplegia via the aortic root. The complications resulting from the technique of retrograde coronary sinus perfusion are rare. Nursing considerations specific to the potential complications of this patient population are discussed. PMID- 2192760 TI - Laryngeal cancer and asbestos. PMID- 2192761 TI - Prevalence of hypodontia and developmental malformation of permanent teeth in Saudi Arabian schoolchildren. AB - This study was carried out to determine the prevalence of hypodontia and congenital malformation in permanent teeth of Saudi Arabian male children. Five hundred schoolchildren were investigated, selected randomly from Riyadh city. The age group of the examined sample ranged from 13 years and 6 months to 14 years and 6 months. Clinical and radiographic examinations were performed. The findings indicated that hypodontia was present in about 4 per cent of the children; most frequently affected was the mandibular second premolars, maxillary laterals, and maxillary second premolars. Tooth malformations, mainly peg-shaped upper lateral incisors were also observed in about 4 per cent of the sample. PMID- 2192762 TI - The effects of recycling on the tensile bond strength of new and clinically used stainless steel orthodontic brackets: an in vitro study. AB - The tensile bond strength was evaluated for three different types of stainless steel orthodontic bracket/base combinations (both cast and machined integral bases, and a foil-mesh base). The cast base gave a significantly higher initial bond strength than the other two brackets. Following recycling by either chemical or thermal methods, all the bases demonstrated a significant reduction in bond strength. However, thermal recycling produced an unacceptably large reduction in the bond strength of the cast base and this method of reconditioning should be avoided with these brackets. Recycling the brackets an additional four times was found to result in a further reduction in bond strength, but this was not statistically significant. Clinically used brackets demonstrated a slightly lower, though not statistically significant, bond strength compared to unused brackets following one recycling with either the chemical or thermal method. PMID- 2192763 TI - An osseointegrated implant to replace a missing lateral incisor following orthodontic treatment. PMID- 2192764 TI - Chronic and endogenous regulation of insulin receptors by catecholamines in adipocytes from patients with a phaeochromocytoma. AB - Insulin binding in adipocytes from patients with a phaeochromocytoma (PH) approached that of the controls (C) at low and higher concentrations of unlabeled insulin. The apparent receptor affinity was unchanged (ED50: PH 0.50 x 10(-9) M and C 0.60 x 10(-9) M). Scatchard analysis of the binding data using the negative cooperative model revealed a 46% decrease in the total number of receptors together with no changes in both K-e (PH 0.55 x 10(9) M-1 and C 0.36 x 10(9) M-1) and K-f (PH 0.13 x 10(9) M-1 and C 0.07 x 10(9) M-1). According to the two site model, an altered proportion in the two classes of insulin binding sites was detected. This was accompanied by a catecholamine-desensitization of the adipocytes to the antilipolytic action of insulin. These events could represent a final situation of a chronic and endogenous regulation by high levels of catecholamines of insulin receptors in human adipose tissue. PMID- 2192765 TI - Diabetes is not associated with a change in the elemental composition of the pancreatic B cell in diabetic C57BL KsJ-db/db mice. AB - Freeze-dried pancreas sections from 7-, 17- and 27-week-old genetically diabetic (db/db) and normal (+/-/+/-) mice were subjected to proton bombardment and the concentrations of 15 elements in B cells and exocrine pancreas were calculated from the characteristic X-rays emitted. In the 7-week-old diabetic animals, B cells contained significantly above-normal levels of Na and S, while exocrine pancreas contained subnormal levels of Ca, and excess Mn. The B cells from the 17 week-old diabetic animals contained subnormal levels of Cu and the exocrine pancreas of the 27-week-old diabetic animals was deficient in Cd. The 7-, 17- and 27-week-old, genetically diabetic (db/db) mice were hyperglycemic, hyperinsulinemic and heavier than age-matched normal (+/-/+/-) mice. Although significant changes were found in elemental composition when comparing both B cells and exocrine pancreas at different ages, the changes were not consistent. Therefore, it appears as if the measured elemental changes were random and not related to the onset of diabetes. PMID- 2192766 TI - Serum theophylline analysis by isotope dilution mass spectrometry. AB - Serum theophylline analysis was attempted using stable isotope dilution mass spectrometry. Theophylline 15N-labelled in position 7 was used as internal standard. The analysis was performed at resolution 3000 by selected ion monitoring with temperature programming. The sample was introduced in underivatized form by means of the direct inlet probe. Good linearity was obtained in the concentration range 5-40 micrograms ml-1 with relative standard deviations less than 6%. The method is simple and permits six samples to be run per hour. Sensitivity permits analysis at 0.5 micrograms ml-1 at a signal to noise ratio 4:1. PMID- 2192767 TI - Intranuclear localization of the Ki-67 reactive antigen in HeLa cells. Flow cytometric analysis. AB - The intranuclear localization of the Ki-67 reactive antigen was immunocytochemically investigated using flow cytometry. HeLa S3 cells were immunocytochemically stained with the monoclonal antibody, Ki-67, after in situ treatments with various kinds of compounds, namely: HCl; NaCl; RNase; S1 nuclease and DNase I. The only treatment that markedly diminished the immunofluorescence intensity of the cells was exposure to DNase I. Nuclear fluorescence was no longer observed in the cells digested with relatively high concentrations of DNase I. These results suggest that the antigen recognized by Ki-67 is closely associated with DNA, but is not directly associated with either the nuclear matrix or histones. PMID- 2192768 TI - The role of the vimentin intermediate filaments in rat 3Y1 cells elucidated by immunoelectron microscopy and computer-graphic reconstruction. AB - The three-dimensional arrangement of vimentin intermediate filaments (IF) was studied in 3Y1, rat fibroblastic cell line, to elucidate its biological role in the cell. While actin filaments were observed exclusively in the superficial part of the cell, vimentin IF were found to be abundantly present in the inside of the cell where microtubules were occasionally discovered. By whole-mount immunoelectron microscopy and computer-graphic reconstruction of serial thin sections, it was observed in more detail that vimentin IF are located very close to the nucleus, endoplasmic reticulum, and mitochondria. Vimentin IF were observed to be attached to these organelles laterally or terminally. Thus, we can reasonably assume that vimentin IF are major cytoskeletal structures deep inside the cell and that they play an important role in supporting the location of the organelles. This is the first report which has visualized the three-dimensional relationship between vimentin IF and the organelles of the cell. PMID- 2192769 TI - Immunochemical localization and association with spermatozoa of androgen regulated proteins of MR 24000 secreted by the mouse epididymis. AB - A polyclonal monospecific immune serum was raised against androgen-regulated proteins with Mr 24000 secreted by the mouse caput epididymidis. Sections of frozen tissues from the different regions of the epididymis have been studied by indirect immuno- fluorescence. Results indicate that the antigens are secretory proteins produced by the epithelial cells of the caput epididymidis, essentially in the medial and distal segments. Accumulation of the antigens was observed in the lumen of the caput and the corpus epididymal duct. Subsequently, their association with the sperm surface occurred and persisted down to the cauda epididymidis. PMID- 2192770 TI - Hip joint ultrasonography: correlation with intra-articular effusion and synovitis. AB - The ultrasonographic distance between the collum of the femur and the capsule of the hip joint was measured in 88 hips of 75 patients with chronic inflammatory joint disease and with hip joint symptoms or signs. In addition, 10 other hips were measured before soft tissue operation of the hip joint. The ultrasonographic distance was 7 mm or more in 29 out of 33 hips with synovial fluid in joint puncture and in seven out of nine hips with intra-articular effusion or synovitis in open surgery. Intra-articular injection of corticosteroid resulted in a significant decrease in the enlarged ultrasonographic distance, in joints both with and without synovial fluid. Joints not treated with steroid did not show any change. It is concluded that both joint effusion and synovitis without effusion can increase the anechogenic distance between the bone and the joint capsule. PMID- 2192771 TI - Failure of selenium-ace to improve osteoarthritis. AB - Selenium-ACE, a formulation containing the trace element selenium with three vitamins, is widely promoted for the treatment of arthritis. A controlled double blind trial of Selenium-ACE in osteoarthritis failed to demonstrate any significant efficacy for the compound over placebo at 3 or 6 months though there was a non-significant trend to improvement in some clinical parameters in both groups. Side-effects were more frequently seen in the placebo group. PMID- 2192772 TI - Autoradiographic studies in animal models of hemi-parkinsonism reveal dopamine D2 but not D1 receptor supersensitivity. II. Unilateral intra-carotid infusion of MPTP in the monkey (Macaca fascicularis). AB - The selective dopaminergic antagonist ligands [3H]SCH 23390 and [3H]sulpiride were used to reveal autoradiographically dopamine D1 and D2 receptors, respectively, in brain sections from monkeys which had received unilateral intracarotid infusions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), causing loss of dopamine-containing neurones of the substantia nigra pars compacta. The monkeys developed hemi-parkinsonian symptoms (tremor, bradykinesia) in limbs contralateral to the side of the toxin infusion. Administration of apomorphine (0.05-0.25 mg/kg) caused contralateral rotational behaviour, and reversal of the parkinsonian symptoms. Loss of forebrain dopaminergic terminals was assessed autoradiographically using [3H]mazindol to label dopamine uptake sites. A reduction in these sites of 97% (mean brain value) in the caudate nucleus, and 91% in the putamen, as compared with binding values from untreated control monkeys, was accompanied by a significant increase in the binding of [3H]sulpiride (D2) in these structures. In contrast, in the same animals there was no similar increase in [3H]SCH 23390 binding to D1 receptors in the denervated areas. These results suggest that in the parkinsonian brain, where the dopaminergic innervation of the caudate nucleus and putamen has been lost, D2 receptors may be more susceptible than D1 receptors to changes, revealed here as an increase in [3H]sulpiride binding sites. PMID- 2192773 TI - Pavlov as a psychophysiological scientist. AB - It is suggested that Pavlov was not only a famous physiologist, but due to his work on the conditional reflex, he could be considered a behavioral scientist. In addition his work on experimental neurosis gives him the distinction of being a pioneer investigator in the area of psychological stress. Pavlov's research is viewed against a background of primitive research tools and unproductive subjective theories. Nineteenth century scientists who influenced Pavlov included Darwin, Botkin, Heidenhain, Gaskell and Bernard. Pavlov's research on the digestive system emphasized the role of the nervous system, launched the field of gastroenterology, and emphasized the concept of the conditional reflex. Pavlov's conditional reflex formulations were based on the theoretical formulations of Sechenov, and possibly the work of David Hartley. The discovery of secretin, by Bayliss and Starling, and its influence on the stomach led Pavlov to diminish his work on the digestive system and to focus his research on the conditional reflex phenomenon. Arguments which suggest that Pavlov worked as a behavioral scientist include his conceptual formulations, his research on traditional psychological topics and his investigation of psychiatric disorders. His conditioning research emphasized the individual differences of his animal subjects which led to his research on typology and experimental neurosis which formed the basis for his work on environmental stressors and psychopathology. PMID- 2192774 TI - Unpredictable and uncontrollable stress impairs neuronal plasticity in the rat hippocampus. AB - Almost by definition, learning and the effect of stress on learning represent modifications of existing neuronal circuitry. Under some circumstances, this modification can be measured electrophysiologically. One such measure of plasticity is long-term potentiation (LTP), a long-lasting increase in synaptic efficacy following brief exposure to tetanic stimulation. In 1987, Foy et al. reported that hippocampal LTP was impaired by exposure to inescapable shock. We have recent evidence that the impairment in LTP can be prevented by allowing the animal to learn to escape the shock (Shors et al., 1989), indicating that the stress effect is to some extent mediated by "psychological" variables. Regardless of LTP's putative role in learning and memory processes, such a stress-induced decrease in neuronal plasticity is likely to have profound effects on the behaving organism. PMID- 2192775 TI - Microangiopathy, the vascular basement membrane and Alzheimer's disease: a review. AB - The present review focuses on the vascular basement membrane (VBM) and its relationship to the lesions of Alzheimer's disease (AD). Examination of the fine structure of the microvasculature reveals AD-associated VBM alterations, which include both thickening and vacuolization. Immunocytochemistry confirms that all three intrinsic VBM components [collagen type IV, laminin, and heparan sulfate proteoglycan (HSPG)] outline the capillary bed, which is pathologically altered in AD patients (microangiopathy). Ultrastructural analyses of AD tissue samples demonstrate that HSPG's normal staining pattern is disrupted on the endothelial surface of the VBM in brain regions affected by Alzheimer lesions. Similarly altered VBM is reported to occur in the kidney of patients with diabetes mellitus, where it is associated with a leakage of protein. All three VBM components immunolabel capillaries, amyloid and plaque-associated glial processes, suggesting a link between microangiopathy and senile plaque formation. In addition, the consistent colocalization of HSPG with several forms of amyloid implies an involvement in amyloidogenesis. Finally, the neurotrophic effects of beta-amyloid, combined with neurite-promoting effects of laminin and HSPG, could create a strong focus for an aberrant sprouting response. Such a response is postulated to result in plaque-associated degenerating neurites. Thus, VBM components could serve as a nidus for plaque formation, playing a role in the development of neuritic as well as amyloidotic elements. PMID- 2192776 TI - [Anaphylactoid reactions during anesthesia and resuscitation]. PMID- 2192777 TI - [Postoperative jaundice. Procedure to follow]. PMID- 2192778 TI - [Per- and postoperative control of increases in arterial pressure during carotid surgery]. PMID- 2192779 TI - Caries predictors suitable for mass-screenings in children: a literature review. AB - This paper reviews the predictors used to identify children and adolescents at high risk of developing dental caries. They are presented with their degree of association with caries, their validity as screening tests and their methods of determination. The most promising predictors are identified and caries prediction models are also briefly reviewed. The article concludes with some comments about weaknesses encountered in the conduct of screening studies and makes some suggestions for improving the validity of the prediction models. PMID- 2192780 TI - Dental screening of long stay geriatric patients in West Essex and recommendations for their care. AB - A dental screening programme at a West Essex Health Authority hospital provided data from 151 in-patients, most of whom were in long-stay geriatric care. 71 per cent were female and the mean age of the geriatric patients was 81 years. 61 subjects (40 per cent) suffered predominantly from mental illness. 107 subjects (71 per cent) were edentulous but a higher proportion of elderly mentally ill patients (42 per cent) had retained some of their natural teeth compared with 20 per cent of the others. 26 edentulous subjects were not in possession of any dentures and the standard of oral and denture hygiene was poor. 59 in-patients (39 per cent) had 'expressed' need for dental treatment and a further 51 (34 per cent) were unable or unwilling to communicate their need. An important aspect of their dental care was the provision and maintenance of a preventive dental programme for both dentate patients and denture wearers. PMID- 2192781 TI - Recent advances in pathogenesis of allergic alveolitis. AB - The animal-model studies discussed above appear to suggest that AA develops as the result of a complex series of immunologically specific events, involving initial sensitization, and the development of granulomatous inflammatory response by a series of genetically determined immunostimulatory events. Modulation of experimental granulomatous lesions by several of the means previously discussed may offer some important clues to the incidence and clinical course of AA in man and to future therapy and/or prevention of the disease. For example, in the animal models discussed previously in which chronic exposure to aerosolized antigen resulted in specific 'desensitization' it is possible that such repeated challenge in man may be refined to the point of inducing similar lengthy refractory periods and a decrease in pulmonary inflammation. The demonstration that hypersensitivity-type pulmonary granulomas in mice are markedly suppressed by inhibitors possessing antilipoxygenase activity, such as nafazatrom and nordihydroguairetic acid and by cyclosporine, may also open the door to investigation of such agents in the experimental treatment of granulomatous pulmonary diseases in man. It is obvious that a better understanding of these mechanisms in man can provide important information to increase our understanding of the possible prevention, modulation, and therapy of chronic granulomatous pulmonary disease. PMID- 2192782 TI - Comparison of a multi-allergen dipstick IgE assay to skin-prick test and RAST. AB - A multi-allergen dipstick enzyme immunoassay 'Quidel Allergy Screen' (QAS) has recently been developed commercially for measuring IgE antibodies against nine allergens (house dust 1, house dust 2, Dermatophagoides pteronyssinus, D. farinae, Japanese cedar, ragweed, cat dander, sweet vernal grass, and egg white) at one time. To assess whether this assay is useful in screening allergen specific IgE antibody, we compared the titres of IgE antibodies against the nine allergens measured by QAS to those in the skin-prick test and by RAST in 93 atopic asthmatics and 22 normal subjects. We found a good overall agreement between the results of the skin-prick test and the results of QAS (sensitivity = 47.1-81.4%, specificity = 84.5-100%, and agreement = 78.9-88.9%). The sensitivities against house dust 1, D. pteronyssinus, and D. farinae ranged from 77.2 to 81.4%. However, the sensitivities against house dust 2, Japanese cedar, ragweed, and cat dander were low (47.1-68.8%). We also found a good overall agreement between the results of RAST and the results of QAS, except for egg white (sensitivity = 46.2-94.4%, specificity = 87.4-100%, and agreement = 77.4 96.5%). The sensitivities against house dust 1 and 2, D. pteronyssinus, D. farinae, and Japanese cedar ranged from 86.0 to 94.4%. The sensitivities against ragweed, cat dander, and sweet vernal grass were low (46.2-52.6%). There were strong correlations between the titres of RAST and the titres of QAS except cat dander and egg white (r = 0.701-0.924 for the seven allergens). Thus, we conclude that QAS is useful in screening IgE antibodies against multiple allergens at one time. However, because the sensitivities against some allergens tested were low, further improvement of some allergen preparations seems to be necessary in the assay. PMID- 2192784 TI - A practical approach to the urticarial syndromes--a dermatologist's view. PMID- 2192783 TI - The relationship between atopy and non-specific bronchial responsiveness. AB - Atopy is often regarded as a risk factor for the development of asthma, particularly childhood asthma and occupational asthma. This could reflect an association with non-specific bronchial responsiveness (NSBR), though atopy could influence asthma independently. We have evaluated the possible relationship between atopy and NSBR (PD20FEV1 to methacholine) in the siblings of 59 probands with atopic asthma. Thirty-four (58%) were atopic (greater than or equal to 1 prick test with weal diameter greater than or equal to that of a 0.1% histamine control) and 28 (47%) showed NSBR. Atopy and NSBR occurred together more frequently than would be expected by chance (P less than 0.05); both variables being observed in 20 subjects, neither in 17, and only one in 22. A significant association was also noted when atopy was defined by a serum total IgE greater than 150 IU (or greater than 50 IU), but when atopy was defined by other commonly used criteria (greater than or equal to 2 prick tests with weal diameter greater than or equal to histamine control; or weal diameter 2 mm or more greater than a saline control), no significant association was demonstrated. Furthermore, linear logistic regression and multiple regression analyses showed that both the presence and the degree of NSBR were influenced much more by the baseline level of FEV1 than by atopic status. At best, atopy accounted for 10% of the variance of the PD20 measurements. We conclude that atopy is associated with NSBR but not strongly; that the relationship may be readily obscured according to the defining criteria used for atopy; and that atopy should not be used as a marker for NSBR. PMID- 2192785 TI - The immune response in a cat-related outbreak of Q fever as measured by the indirect immunofluorescence test and the enzyme-linked immunosorbent assay. AB - The isotypic immune response of 16 individuals who developed Q fever pneumonia following exposure to an infected parturient cat was studied. The enzyme-linked immunosorbent (ELISA) test was used to detect IgM, IgA, and IgG antibodies to phase I and phase II Coxiella burnetii whole-cell antigens and to the phase I lipopolysaccharide. The indirect immunofluorescent antibody (IFA) test was also used to detect antibodies to phase I and phase II whole cells. None of the 16 subjects developed antibodies to the phase I lipopolysaccharide. The ELISA was more sensitive than the IFA test. IgM antibodies to phase II antigen were detectable by ELISA in 80% of the subjects at the time of onset of symptoms and were still present in 7 of the 8 tested at 32 weeks following the onset of symptoms. In all instances (ELISA: IgG, IgM; IFA: IgG, IgM) phase II antibodies developed earlier and reached higher levels than did phase I antibodies. The absence of antibodies to phase I lipopolysaccharide in acute Q fever combined with our unpublished findings of antibodies to phase I lipopolysaccharide in chronic Q fever suggests that this test may be used to distinguish acute from chronic Q fever. PMID- 2192786 TI - Aerobactin uptake system, ColV production, and drug resistance encoded by a plasmid from an urinary tract infection Escherichia coli strain of human origin. AB - A study of Escherichia coli strains isolated from patients suffering from urinary tract infections in Ljubljana, Yugoslavia, revealed a plasmid encoding the aerobactin iron uptake system, ColV production, and drug resistance. The plasmid is conjugative and at least 85 kilobases in length. PMID- 2192787 TI - Drug-induced parkinsonism and other movement disorders. AB - This is a review of reserpine, haloperidol, and various phenothiazines that produce parkinsonism and other movement disorders. The by-products of illicit meperidine synthesis, MPTP and its more sinister companion, MPP, are also discussed. Movement disorders, transient or fixed, frank parkinsonism and/or dyskinesia, due to a variety of other medications and toxic agents are included. These are methanol, lithium, methyldopa, antimetabolites, antidepressants, sympathomimetic anorexiants, some types of antihistamines, and various combinations of agricultural chemicals. PMID- 2192788 TI - Mechanisms of tumor-associated edema: a review. AB - An understanding of the mechanisms responsible for tumor-associated edema involves the elucidation of the role played by a number of intra-related processes. These include (i) the permeability of new tumor microvessels that are associated with tumor angiogenesis; (ii) alterations in microvascular permeability due to factors secreted by tumor cells; (iii) immunological mechanisms and (iv) increased microvessel permeability associated with inflammation. The rationale for a role for inflammatory processes in tumor associated edema has been outlined and the role of non-steroidal anti inflammatory drugs in modulating experimental and human tumor-associated edema has been explored. PMID- 2192789 TI - Correlation of CT and MR with impedance monitoring and histopathology in stereotactic biopsies. AB - Magnetic Resonance Imaging (MR) and Computer Assisted Tomography (CT) guided stereotaxis combined with intraoperative impedance monitoring and multiple sequential biopsies provides the opportunity to correlate the results of radiologic imaging with impedance and histopathology. The authors present the methods used and preliminary results obtained from 30 stereotactic biopsies with complete correlation in 12 cases. Impedance changes correlate accurately with lesion margins as defined by histology. CT images of enhancing lesions correlate quite closely to the histopathologic lesion margins whereas the appearance of the lesion on MR images is often larger than subsequently identified by either impedance or at pathologic examination. Impedance monitoring is a useful adjunct to stereotactic biopsy as it helps to accurately define lesion margins and can help direct the choice of biopsy sites. PMID- 2192790 TI - Critical appraisal of experimental radiation modalities for malignant astrocytomas. AB - The management of patients with supratentorial malignant astrocytomas has remained a major problem. Patients continue to die from a lack of local control in 90% of cases despite an improvement of median survival seen with the use of postoperative radiation therapy. Because of this, there has been considerable interest in exploring novel ways of possibly improving results. This paper reviews the rationale and clinical results with the use of altered fractionation schemes, brachytherapy, radiation sensitizers, hyperthermia, particle therapy, and radiosurgery in the treatment of these patients. Currently, there is no demonstrated advantage with the use of these experimental modalities in the initial management of patients. There would appear to be some benefit for selected patients who are treated with brachytherapy at recurrence, but its efficacy as part of initial management remains to be determined determined in ongoing randomized prospective trials. PMID- 2192791 TI - Accurate, reproducible measurement of blood pressure. AB - The diagnosis of mild hypertension and the treatment of hypertension require accurate measurement of blood pressure. Blood pressure readings are altered by various factors that influence the patient, the techniques used and the accuracy of the sphygmomanometer. The variability of readings can be reduced if informed patients prepare in advance by emptying their bladder and bowel, by avoiding over the-counter vasoactive drugs the day of measurement and by avoiding exposure to cold, caffeine consumption, smoking and physical exertion within half an hour before measurement. The use of standardized techniques to measure blood pressure will help to avoid large systematic errors. Poor technique can account for differences in readings of more than 15 mm Hg and ultimately misdiagnosis. Most of the recommended procedures are simple and, when routinely incorporated into clinical practice, require little additional time. The equipment must be appropriate and in good condition. Physicians should have a suitable selection of cuff sizes readily available; the use of the correct cuff size is essential to minimize systematic errors in blood pressure measurement. Semiannual calibration of aneroid sphygmomanometers and annual inspection of mercury sphygmomanometers and blood pressure cuffs are recommended. We review the methods recommended for measuring blood pressure and discuss the factors known to produce large differences in blood pressure readings. PMID- 2192792 TI - Grosse Ile: the Isle of Sorrows recalls the plague years. PMID- 2192793 TI - Cytogenetics of human brain tumors. AB - The most frequent cytogenetic alterations in primary brain tumors are losses of chromosomes or chromosomal regions and the presence of double minute chromosomes (dmins). The regions which are lost and the genes which are amplified are distinctive for individual tumor types. Most malignant gliomas contain gains of chromosome 7 and losses of chromosome 10; losses of chromosome 22, 9p, and the sex chromosomes occur in subgroups of cases. The gene most frequently amplified in tumors with dmins is the epidermal growth factor receptor gene. Medulloblastomas have losses of 17p and most cases with dmins have c-myc gene amplification. Meningiomas have losses or deletions of chromosome 22. Identification of these specific cytogenetic abnormalities in human brain tumors has provided the framework for identifying genes which are amplified in them and has identified chromosomal regions likely to contain tumor suppressor genes, the loss or inactivation of which is important in the development of these tumors. PMID- 2192794 TI - Convulsive disorders: the use of anticonvulsant drugs. PMID- 2192795 TI - Open trial of a calcium antagonist, nimodipine, in acute mania. AB - Following previous works showing an action of calcium channel blockers in mania, this trial explores the clinical efficiency of another anticalcic agent, nimodipine, which has been selected for its specific action on the CNS. Our design has been a 7-day controlled open trial. We included six inpatients diagnosed according to DSM III-R criteria as having mild to acute mania. Evaluations have been made by clinical scales, electroencephalography, electrocardiography, and extensive biological blood tests. No other medication than nimodipine was allowed excepted i.m. droperidol in case of severe excitement. We used nimodipine at a dose of 360 mg/day. The results showed good clinical efficiency in each of our six inpatients, with an important and significant improvement of scales scores. We noticed an early and significant action on mood without important sedative effect. The treatment has been well tolerated, without biological effects. Further studies are needed, but nimodipine could be an alternative treatment to the neuroleptics with a different type of action, less sedative and more specific on mood. PMID- 2192796 TI - Transoral labiomandibular approach to basiocciput chordomas in childhood. AB - Many excellent reports have dealt with the various aspects of cranial chordoma. It remains a relatively rare neoplasm, particularly in younger children. The authors have had the opportunity to treat a 5-year-old child harboring a basiocciput chordoma. It extended from the mid-clivus to C3. A transoral labiomandibular approach was used, allowing its resection. No evidence of recurrence was noted 3 years later. A literature search confirmed the rarity of basiocciput chordoma in young children. The perioperative difficulties encountered prompted this report. PMID- 2192797 TI - Subacute traumatic extradural haematomas of the posterior fossa: a clinicopathological entity of the 5- to 10-year-old child. AB - The subacute form of posterior fossa extradural haematoma, which presents a few days after minor occipital trauma, is a distinct clinicopathological entity that occurs most commonly in the 5- to 10-year-old child. Five cases are presented and the literature is reviewed since the advent of computed tomography. PMID- 2192798 TI - Magnetic resonance evaluation of spinal dysraphism in children. AB - Magnetic resonance (MR) imaging of the spine was performed as the initial imaging technique in 20 children when spinal dysraphism was suspected clinically and plain radiographs showed spina bifida. The correlation with surgical findings indicated that MR provided accurate information preoperatively in all the cases. Some unusual observations in cases with spina bifida cystica and occulta are discussed. It is concluded that plain radiograph and MR complete the preoperative radiologic evaluation of cases with spinal dysraphism. PMID- 2192799 TI - Multicell spheroids as a model for cell kinetic studies. AB - Cells growing in tissue culture as three-dimensional, multicellular aggregates called 'spheroids' typically show a decreasing growth fraction and development of quiescent subpopulations as the spheroids enlarge. Kinetic studies in a number of spheroid systems have indicated that the primary reason for the tumour-like growth is a progressive decrease in growth fraction, with only a modest elongation of cell cycle time in larger spheroids. In this paper, the cellular growth kinetics for spheroids of V79 Chinese hamster lung cells are reviewed, and the regrowth kinetics of cells resuming growth after recovery from quiescent regions of the spheroids are described. Further, the role of regrowth/repopulation in determining the spheroid response to anti-tumour cytotoxics is explored, with particular emphasis on treatment with cisplatin and etoposide. By separating the effects of cytotoxicity and regrowth in the overall spheroid response to anti-neoplastic drugs, it is suggested that 'drug resistance' in tumours can be a kinetic as well as a genetic problem. PMID- 2192800 TI - A reproducible technique combining tritiated thymidine autoradiography with immunodetection of bromodeoxyuridine for double labelling studies of cell proliferation in paraffin sections of tissues. AB - A method is described to combine tritiated thymidine autoradiography with immunoperoxidase detection of bromodeoxyuridine on the same paraffin sections. It overcomes the varied technical artefacts we encountered when first attempting to combine these techniques and results in preparations with extremely low peroxidase and autoradiographic backgrounds. In particular, we find it is important to avoid the use of detergents during immunostaining, otherwise grain counts are reduced and autoradiograph exposures need to be greatly increased, and to avoid excessive peroxidase staining which makes it difficult to visualize silver grains in the overlying emulsion. The advantages of a method to remove emulsion films using acid-alcohol, allowing the same sections to be dipped twice with a long and a short autoradiographic exposure, are presented. The routine combination of high quality tritiated thymidine autoradiography with clean immunoperoxidase staining of bromodeoxyuridine-positive nuclei provides a new and powerful cell kinetic, double-labelling method to augment existing techniques e.g. by labelling the same cells undergoing DNA synthesis in successive cell cycles. PMID- 2192801 TI - President's report. 125 years in review. PMID- 2192802 TI - Insulin induces cell adhesion and normal flattened morphology in Krebs II ascites tumour cells. AB - Insulin induced Krebs II ascites cells to attach to the substratum and to adopt a flattened morphology associated with normal adhesion and movement. The changes were associated with a reorganization of cellular actin. The results show that insulin has important effects on cell structure and morphology. Insulin may thus be involved in the nutritional control of normal and malignant growth. PMID- 2192803 TI - An antibody to S1 proteins from rat liver. AB - S1 proteins (A, B, C and D) are a group of nuclear proteins, isolated by lowering pH to 4.9 of the reaction supernatant of hepatocyte nuclei that had been mildly digested with DNase I. Protein B, apparently ubiquitous in vertebrate cells, was prepared from rat liver and used to immunize a rabbit. The raised antiserum specifically reacted with S1 proteins; it reacted not only with protein B, but also with C and D. Immunoblotting demonstrated that these proteins occurred exclusively in the nucleus, being absent in the cytosol, microsome and mitochondrial fractions. Indirect immunofluorescence of liver tissue sections confirmed their nuclear localization, and further showed that the antibody selectively stained extranucleolar regions of the cell nucleus. These findings suggest that the anti-S1 antibody is specific to S1 proteins and may be useful for their structural and functional studies. PMID- 2192805 TI - Interactions between the yeast mitochondrial and nuclear genomes: isogenic suppressive and hypersuppressive petites differ in their resistance to the alkaloid lycorine. AB - In a previous paper we have shown that the alkaloid lycorine inhibits growth of rho+, mit- and rho-, strains of Saccharomyces cerevisiae, whereas strains devoid of mitochondrial DNA (rho degrees) are resistant to more than 200 micrograms/ml of the alkaloid. In this report we show that hypersuppressive petites are almost as resistant as rho degrees mutants, whereas isogenic rho- petites, which have retained longer segments of the genome, are sensitive to the drug. PMID- 2192804 TI - The genetics of RNA polymerases in yeasts. PMID- 2192806 TI - Verotoxin-producing Escherichia coli in ground beef--Manitoba. PMID- 2192807 TI - [Complications in the disinfection and sterilization of dental instruments and the clinical significance]. PMID- 2192808 TI - [Results of systematic preventive treatment with argon laser after idiopathic retinal detachment]. AB - Incidence of spontaneous second retinal detachment ranged from 10 to 19%. We reported a retrospective study of 527 rhegmatogenous retinal detachments. At the end of this study 302 second eyes with an average follow up of 46 months have been analysed. 205 second eyes were treated systematically by 360 degrees equatorial Argon Laser Photocoagulation (ALP) completed by four anterior radial rows independently of evidence or lack of peripheral retinal degenerations or retinal breaks. The incidence of bilateral retinal detachment decreased from 11 to 2.4% when systematical prophylactic treatment has been applied. After prophylactic treatment, no complications could be certainly attribute to ALP. This study contributed to ascertain safety and effectiveness of systematical prophylactic treatment by ALP. PMID- 2192809 TI - [Melanoma of the uvea in young patients. Apropos of 3 cases]. AB - The authors report 3 cases of uveal melanoma, appeared on young women: 20, 23 and 28 years old. The melanomas were localized on the iris, the ciliary body and on the choroid. The authors studied the different notions of the literature about happened age of these lesions. PMID- 2192810 TI - [Syphilitic uveitis]. AB - The incidence of syphilitic uveitis is reportedly increasing, up to 1% uveitis in general, with often polymorphic and atypical manifestations. Three cases of syphilitic uveitis are reported here, at different stages (secondary, latent, late). The bacteriologic sterilization is often unlikely in ocular syphilis, and recurrence is frequent; therefore a high-dose intravenous penicillin G treatment is then to recommend. HIV serology must be systematically associated with syphilitic tests. PMID- 2192811 TI - [Electrophysiologic aspects of amblyopia]. PMID- 2192812 TI - Carboplatin is ototoxic. AB - For assessment of the ototoxic potential of carboplatin [cis-diammine-1,1 cyclobutane dicarboxylate platinum(II); CBDCA], pure-tone audiograms were evaluated in 27 patients receiving a total of 119 doses of carboplatin in the range of 300-400 mg/m2. Pure-tone audiometry (PTA) was done immediately prior to and 4 weeks after the administration of 80 doses (67%). Defining carboplatin ototoxicity as an increase of greater than or equal to 30 dB in auditory thresholds that was unexplainable by other causes, we identified 5 examples (19%). Hearing loss tended to be cumulative with increasing dose and was always maximal at 8,000 Hz. Two patients had an increase in auditory thresholds at 1,000 Hz, but this only amounted to 10 dB in each case. Patients developing ototoxicity tended to be older. Sex, the pre-treatment creatinine clearance, the pretreatment audiogram, the number of doses, and the cumulative dose did not emerge as being reliable predictors of subsequent ototoxicity. We conclude that although carboplatin is ototoxic, clinically significant deafness does not occur with conventional dosing and routine audiometric monitoring is therefore unnecessary. However, we suggest that caution should be exercised when carboplatin is given either at higher doses or for longer periods when there is concomitant use of other potentially ototoxic agents or when there is significant pre-existing auditory impairment. PMID- 2192813 TI - Cardiac dysfunction in a rat model of chronic bacteremia. AB - Cardiac function was examined in vivo and in vitro in rats to determine if cardiac dysfunction could be demonstrated in a nonlethal model of infection. Bacteremic rats (n = 6) had a subcutaneous polymicrobial abscess produced via repeated inoculations of an encapsulated foreign body with Escherichia coli, Bacteroides fragilis, and Staphylococcus aureus while control rats (n = 6) had the same subcutaneous, encapsulated foreign body (an inflammatory focus) but were not inoculated with bacteria. Cardiovascular function was assessed indirectly in vivo by measuring the maximal O2 uptake during a progressive exercise test in both groups before and 14 days after the initiation of inoculations. Cardiac function was also assessed in vitro in the same rats by measuring stroke volumes generated at six different preloads with constant heart rate and afterload. Bacteremic rats had a significantly different fever curve and leukocytotic response than control rats over the 14 day period. The majority of rats that received inoculations demonstrated bacteremias, while none of the control animals had positive cultures for the inoculated organisms. Although in vivo assessment of cardiovascular function showed no evidence of dysfunction, in vitro assessment demonstrated a significant rightward shift of the Starling curve in bacteremic rats. These data suggest that LV dysfunction occurs even during nonlethal infections but may be masked in vivo by compensatory mechanisms. PMID- 2192814 TI - Unexpected hyperactivity of myocardial adenylate cyclase system in endotoxic male rats. AB - Ventricle beta-adrenoceptors have been investigated and serum steroid levels determined in male rats injected intravenously with lipopolysaccharide from E. coli (LPS) under light anesthesia. Two series of doses were successively studied: 1) 2 and 3 mg.kg-1 and 2) 1 and 4 mg.kg-1, each including controls. The second series was carried out owing to the unexpected results of the first one. Homogeneity of the two series was tested. Experiments were performed at hr 4 after injection, a time previously tested to induce hormonal variations and release of a cardiodepressant factor (CDF) in serum. The results indicate that 2 mg.kg-1 LPS induced an increased activity of adenylate cyclase. The unexpectedly high response was dose-dependent since it was not found with the lowest or highest doses. The determination of serum steroid levels (progesterone, 17 alpha hydroxyprogesterone, corticosterone, delta 4-androstenedione, testosterone, estrone, and estradiol) was used as a kind of marker of endotoxin activity. The results point out that the light anesthesia used for LPS injection delayed the hormonal response, when compared with results previously obtained with the same LPS dose (2 mg.kg-1) in unanesthetized rats. It can be inferred that the present data should usually appear at an earlier stage. It is suggested that an endotoxin induced protein kinase C activation could be involved in the observed hyperactivity of adenylate cyclase and the hyperdynamic phase of septic shock. PMID- 2192815 TI - Direct correlation between injury severity and two markers of the functional status of the immune system. AB - This study was conducted to identify a relationship between anatomical trauma severity and immunologic function. Four milliliters of citrated whole blood (CWB) was obtained from 14 multiply traumatized patients and their Injury Severity Score (ISS) was calculated. Each CWB sample was divided into four 1 ml aliquots with 1 microgram of E. coli endotoxin (ECE) (Difco) being added to the first, 10 micrograms of ECE to the second, 10 micrograms of pokeweed mitogen (PWM) to the third, and 20 microliters of saline to the fourth. Following a 2 hr incubation at 37 degrees C the recalcification time (RT) was determined on a Hepcon-B10. Percent shortening was calculated as the difference in the RT between the stimulated sample and the saline control. There was a significant correlation between ISS and % shortening of the ECE stimulated samples at both concentrations (for 1 microgram ECE r = 0.59, P = 0.02, and for 10 micrograms ECE r = 0.81, P = 0.00025), and also in the PWM sample (R = 0.79, P = 0.00071). This study demonstrates a significant and direct relationship between trauma severity and the patient's monocytes' ability to generate thromboplastin following ECE or PWM stimulation. PMID- 2192816 TI - Does heparin improve survival in experimental porcine gram-negative septic shock? AB - To evaluate the effects of heparin on gram-negative septic shock, immature piglets were subjected to fecal Escherichia coli peritonitis. One group of animals received a continuous infusion of heparin 25 units/kg/hr, while the control animals were given an equivalent volume of lactated Ringer's solution. Heparin-treated animals (n = 5) had a mean survival time (+/- SEM) of 18.8 +/- 2.2 hr vs. 11.9 +/- 2.8 (P less than 0.05) in controls (n = 5). Animals receiving heparin tended to have improved hemodynamic profiles and less leukopenia than controls. PMID- 2192817 TI - Glucoregulatory, hormonal, and metabolic responses to endotoxicosis or cecal ligation and puncture sepsis in the rat: a direct comparison. AB - This study characterized the cecal ligation and puncture (CLP) model of sepsis and the bolus endotoxin model of sepsis in rats with regard to specific hormonal, metabolic, and glucoregulatory changes which occur during the early, compensatory phases of sepsis. Plasma levels of glucose, lactate, insulin, and glucagon were measured during the initial 5 hr of endotoxicosis and CLP sepsis. During this time period, endotoxic and CLP septic rats displayed similar metabolic changes, particularly hyperglycemia, hyperlactacidemia, hyperinsulinemia, and hyperglucagonemia relative to their respective control groups. The metabolic and hormonal similarities observed between these two models of sepsis are consistent with the concept that endotoxin plays a role as a mediator of human and animal sepsis. PMID- 2192818 TI - Androgen assessment in hirsutism and alopecia. AB - Advances in technology, such as saturation analysis and nonisotopic immunoassays, have improved the measurement of androgens, binding proteins, and hormone receptors, and clarified the diagnosis of idiopathic hirsutism. Immunoassay methods in steroid biochemistry enable accurate measurement of low concentrations of various androgens and their metabolites; and high-specificity antisera with chemical blocking agents allow measurement of these steroid directly in plasma without resorting to extraction methods. The future may bring the capacity to measure free concentrations. PMID- 2192819 TI - Long day lengths promote brain growth in meadow voles. AB - Male meadow voles kept in a long photoperiod (LP) from birth to 70 days of age have heavier brains than those kept in a short photoperiod (SP). Brain weights of male voles kept in the LP first exceeded those of SP animals at 20 days of age; differences were greatest at 35 days (5.8%) and persisted through 140 days of age (2%), although the magnitude of the difference declined progressively. Accelerated compensatory increases in brain weight were observed in voles transferred from the SP to the LP at 70 days of age. Total brain DNA content, an index of cell number, was not significantly affected by initial or final photoperiod, although it increased 7.8% within 70 days after voles were transferred from the SP to the LP. Brain weights (but not DNA content) of males exceeded those of females, but this sex difference was present only in the LP. We suggest that short day lengths retard brain development by reducing rates of myelination and possibly reducing cell size as well; this is part of a general retardation of somatic growth associated with a delayed onset of puberty that can be reversed by a stimulatory LP but, ordinarily, occurs spontaneously as voles become refractory to short day lengths. PMID- 2192820 TI - Sexual dimorphism in brain weight of meadow voles: role of gonadal hormones. AB - In most adult mammals, brain weights of males exceed those of females. The role of androgens in the genesis of this sex difference was assessed in meadow voles by acute neonatal or chronic postweaning manipulation of testosterone titers. Female voles given a single injection of testosterone propionate (TP) on the second day of postnatal life had brain weights in adulthood that were indistinguishable from those of male voles and significantly heavier than those of control females. Whole brain DNA content, a measure of cell number, was not increased by neonatal TP treatment. Females treated with TP from day 19 to 70 had lower brain weights than control females and males gonadectomized at 19 days of age had greater brain weights than did intact male voles at day 70. The sex dimorphism in brain weight reflects organizational effects of testosterone during perinatal development. Beginning at weaning, and continuing through postpubertal development, testosterone decreases brain weight in both sexes. We suggest that testosterone affects brain weight by altering cell size or non-cellular components rather than cell number. PMID- 2192821 TI - More on "alpha-electrophoretic form of beta 2-microglobulin". PMID- 2192822 TI - Interference by human anti-mouse antibody in two-site immunoassays. AB - Studies with goat and rabbit anti-mouse antibody, as models of human anti-mouse antibody (HAMA), have shown that several of the commonly used two -site immunoassays (e.g., for CA-125, carcinoembryonic antigen, choriogonadotropin, lutropin, hepatitis B surface antigen, thyrotropin) are susceptible to interference by this type of bridging heterophile antibody. In most cases the interference can be blocked by incubation with mouse IgG. We studied HAMA interference in an assay of hepatitis B surface antigen by using HAMA-positive sera from a transplant patient given OKT3 and from a cancer patient given CYT-103 (modified antibody B72.3). The HAMA interference attributable to the OKT3 could be blocked by incubation with mouse IgG at room temperature. In contrast, the interference caused by the B72.3-induced HAMA could be blocked by prolonged incubation with high concentrations of the B72.3 antibody at 4 degrees C. A limited survey of 50 hospital patients selected without conscious bias revealed two HAMA-positive patients, only one of whom was known to have been exposed to mouse immunoglobulin. HAMA interferences are currently a minor problem in routine laboratory medicine, but the increasing use of diagnostic and therapeutic products involving mouse-origin monoclonal antibodies will make the detection and elimination of HAMA interferences an important part of laboratory practice in the future. PMID- 2192823 TI - Central infusion of aldosterone increases blood pressure by mechanisms independent of Na retention. AB - Experiments were performed to test the hypothesis that Na retention and Na in the diet are not required to initiate central aldosterone induced hypertension. Rats were fed either standard rat chow or Na-deficient diet and infused intracerebroventricularly (i.c.v.) with aldosterone (28 ng/h) dissolved in artificial cerebrospinal fluid (vehicle) or vehicle alone. In Na-replete rats the central infusion of aldosterone did not promote Na or water retention, prior to increases in systolic blood pressure (SBP). Infusion of aldosterone in Na deficient rats also initiated a rise in SBP, although the response was delayed. In neither group of rats did aldosterone infusion significantly change plasma Na, K, renin, norepinephrine (NE) or vasopressin (AVP) concentrations. There was no significant increase in plasma aldosterone concentration in Na replete rats centrally infused with aldosterone. Infusion of vehicle had no effect on SBP. We conclude that central aldosterone infusion initiates an increase in blood pressure by a mechanism independent of Na retention. Furthermore, increased concentrations of systemic renin, vasopressin, and activation of the sympathetic nervous system do not appear to be involved in maintaining hypertension. PMID- 2192824 TI - Relationship between plasma catecholamines and the renin-aldosterone system during exercise in normal and essential hypertensive subjects. AB - Interrelations were investigated between blood pressure, plasma epinephrine (E), norepinephrine (NE), dopamine (D), aldosterone, cortisol concentrations, active and inactive plasma renin activity (PRA), and age in 21 normotensive subjects (aged 20-60 years) and in 25 patients (aged 20-63 years) with essential hypertension (EH). These parameters were measured at rest and during exercise on a bicycle ergometer. In normotensive subjects basal and exercise-stimulated levels of plasma NE increased with age which was not observed in EH. In hypertensive patients there was a higher plasma D concentration under the exercise as compared with normotensive controls. In the normotensives, basal active PRA was inversely related to age (p less than 0.05), and during initial 8 min of exercise active PRA significantly correlated with plasma E and plasma NE. Moreover, absolute changes from basal to acutely stimulated values of active PRA were directly related to the changes of plasma E and NE (p less than 0.001). In hypertensive patients these relationships were not found. However, in the hypertensives there were significant positive correlations between the increases of active PRA, plasma E, plasma NE on the one hand and their respective basal values on the other hand. The results indicate very strong functional relationship between the sympathetic-adrenomedullary and renin-angiotensin systems during initial interval of acute stimulation in normotensive subjects. Essential hypertension is not a pathophysiologically homogenous disease with respect to reactivity and interaction of plasma catecholamines and PRA. Separate regulatory pathways exist for plasma active and inactive renin. During short-time exercise aldosterone secretion is related rather to the renin-angiotensin system than to the hypothalamic-pituitary axis. PMID- 2192825 TI - T cell reactivity to the purified mycobacterial antigens p65 and p70 in leprosy patients and their household contacts. AB - T cell reactivity to the 70 and 65 kD (p70 and p65) protein antigens derived from Mycobacterium bovis BCG strain was studied by measuring the proliferative responses of peripheral blood mononuclear cells from members of an isolated Aboriginal community resident in the Torres Straits islands. In the nine index leprosy cases the pattern of responsiveness to the purified antigens paralleled that to whole sonicates from M. leprae and BCG. In the 40 contacts of the index cases, a high correlation was observed between the responses to p70 and p65 as well as to the crude sonicates. Significant T cell responses to the purified antigens, as well as the crude sonicates, were obtained with cells from the majority of contacts. Limiting dilution analysis of precursor frequencies in the contacts confirmed the immunogenicity of the purified antigens and excluded both a mitogenic component and the presence of suppressor cells in those moderate or low responders whose blood contained sufficient precursors to be tested. p70 appeared to be more potent in stimulating a proliferative response than p65 at equivalent protein concentrations. No correlation between responder status to either antigen and disease type was detected in families. These findings provide confirmation of the importance of p70 and p65 as major T cell immunogens in man and indicate that they are both potential candidates for inclusion in a bivalent vaccine for leprosy and tuberculosis. PMID- 2192827 TI - Structural abnormalities. A systematic approach to diagnosis. PMID- 2192826 TI - Altered monocyte function in uremia. AB - Uremia appears to suppress immune function predisposing patients to infections. When the defect in cellular immunity was studied by exposing mononuclear cells (MNC) from uremic patients and controls to tetanus toxoid, diptheria toxoid, or Candida albicans antigen in vitro, the uremic cells were far less responsive. Monocytes and T cells, which are both involved in the proliferative response to soluble antigens, were isolated from MNC of uremic patients and HLA class II matched controls and incubated with tetanus toxoid. Tetanus toxoid-pulsed uremic monocytes were unable to stimulate the proliferation of HLA identical control T lymphocytes. Lymphocytes from uremic patients, however, were stimulated by tetanus toxoid-pulsed control monocytes. Therefore, the ability of monocytes to function as accessory cells is severely affected by uremia. The uremic monocytes were FcR+, produced IL-1 beta, and expressed levels of HLA class II antigens comparable to controls. Although the biochemical defect in uremic monocytes remains unknown, the abnormality could explain many of the immunological changes of uremia. PMID- 2192828 TI - Captopril in the treatment of chronic CHF. AB - Captopril is an effective oral drug that helps break the cycle of CHF. Improvements in symptomatology, functional capacity and exercise tolerance are seen with long-term therapy. Captopril is an important addition to the present drug therapy of CHF. PMID- 2192829 TI - Modern treatment approaches to vitiligo. AB - Vitiligo is a common disorder for which treatment is frequently difficult and disappointing. The current medical and surgical treatment options are reviewed and fully discussed. Several recently developed therapeutic modalities that may be useful options in the future are described. PMID- 2192830 TI - The necessity for treatment of childhood port-wine stains. AB - The pulsed tunable dye laser has recently become available for the treatment of children with port-wine stains. Parental reactions and psychosocial implications of untreated port-wine stains in children are reviewed. It is recommended that children with port-wine stains be treated as early as possible to prevent adverse sequelae to their psychological development. PMID- 2192831 TI - Physical methods for the management of hirsutism. AB - Physical methods for the management of unwanted hair are critically reviewed. Electrolysis and thermolysis are popular and medically proven electrochemical and electrosurgical techniques for permanent hair removal. Many patients seek consultation with their physician prior to having this elective procedure performed. Clinical guidelines are presented for a successful consultation with such patients. Many years ago the unregulated practice of x-ray therapy by unlicensed and poorly trained personnel resulted in tragic morbidity and mortality. Some historical parallels exist between this disturbing period and present day electrolysis and thermolysis practice: only twenty-seven states currently require licensing for permanent hair removal, which is a procedure with rare but potentially serious complications. PMID- 2192832 TI - Lasers, tissue expansion, and sun protection in pediatric dermatology. AB - As our knowledge of cutaneous disease increases, areas emerge in which our intervention with patients at an early age can significantly alter the progression of disease. This article discusses three major topics of new advances in the treatment of children with cutaneous disorders. These include laser therapy of various skin anomalies, the use of tissue expansion in congenital nevi, and the role of sun protection in children. PMID- 2192833 TI - Cutaneous vascular disorders: advances in laser treatment. AB - The treatment of cutaneous vascular disorders has been undergoing revolutionary changes with the advent of a new generation of highly specific laser systems. Utilizing yellow laser light, it is now possible to destroy ectatic vascular lesions selectively with minimal or no damage to other cutaneous structures. Improved clinical results, reduced pain, and greatly decreased risk of scarring now allow outpatient treatment of patients at any age and with lesions at any anatomical location often using either local or no anesthesia. Children with port wine stains can now be safely treated before they sustain serious psychological damage. Almost all vascular skin lesions can be significantly lightened or removed using yellow laser light therapy. Often the treated areas return to completely normal-appearing skin. New topical anesthetics and automated, "robotic" laser scanning devices allow faster, less painful, and more cost effective treatment. This article critically examines available treatment options, and the indications for and limitations of these treatments. PMID- 2192834 TI - Handling of proteins in isolated and in vitro perfused proximal tubules from rabbit kidney. PMID- 2192835 TI - The haemostatic balance in groups of thrombosis-prone patients. With particular reference to fibrinolysis in patients with myocardial infarction. AB - The concept of the haemostatic balance was reviewed, and its potential role in the regulation of tissue repair and the pathogenesis of thrombotic processes was surveyed. Physiological activation of coagulation appears to be dominated by effects of degenerated and injured cells of the vascular wall causing local release of thromboplastin and exposition of activating surfaces. Inhibition of coagulation impairs its progression and the non-thrombogenic nature of the normal endothelium is chiefly caused by the binding of inhibitory components (antithrombin-III, protein C) to specific receptor sites. Physiological activation of fibrinolysis appears to be triggered by and limited to the fibrin because of a specific affinity to fibrin of plasminogen and plasminogen activators. Systemic activation of fibrinolysis is prevented by primary (alpha 2 antiplasmin) and secondary (alpha 2-macroglobulin, alpha 1-antitrypsin) plasmin inhibitors. A plasminogen binding protein (histidine-rich glycoprotein), plasmin inhibitors and activator inhibitors appear to contribute to the regulation of the initial phase of fibrinolysis. A deviation from normal of the dynamic balance, regulating fibrin formation and resolution, may lead to a haemorrhagic and/or a thrombophilic state. Described were the optimization of selected methods for assessment of variables involved in the haemostatic balance. An overestimation of plasminogen concentrations in plasma may occur in patients with elevated levels of fibrinogen or fibrin degradation products, when using assays based on the activation of plasminogen by streptokinase followed by the hydrolysis of a synthetic chromogenic substrate. This source of error could be eliminated by presence of fibrinogen in excess in the plasminogen assay, thereby securing maximum stimulation of the plasminogen-streptokinase complex. The presence of cryoglobulin in plasma interferes with the assessment in euglobulins of plasminogen activator activities. Experiments indicate that tissue-type plasminogen activator adsorb cryoglobulins and that a cold-promoted activation of the factor XII-dependent proactivator system of fibrinolysis is related to the presence of cryoglobulins. Experiments supported the existence of an as yet not characterized factor XII-dependent proactivator. Strictly optimized procedures for the preparation of euglobulins for the accurate determination of plasminogen activators were recommended. The determination of plasminogen activator inhibition in plasma was optimized and simplified. The amidolytic assay of antithrombin-III was shown to be influenced by adsorption to laboratory utensils and aggregation of thrombin. This error could be corrected by protection with additives (Tween 80, polyethyleneglycol 6,000), which also improved the solubility of the chromogenic substrates in aqueous media. The role of thrombosis in myocardial infarction was reviewed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2192836 TI - Studies of velocity fields and turbulence downstream of aortic valve prostheses in vitro and in vivo. PMID- 2192837 TI - Thyroid size determined by ultrasound. Influence of physiological factors and non thyroidal disease. AB - Grading of goitre size according to WHO or the palpatory estimation of thyroid volume does not allow a quantitative estimation of thyroid size or an objective follow-up during treatment with e.g. radioiodine. The present and other studies have demonstrated that the ultrasonic evaluation of thyroid volume is both accurate and precise. In addition, it is non-invasive, rapid, inexpensive and without discomfort to the patient. Using this technique it was demonstrated that thyroid volume increases with increasing age and body weight in both sexes, with weight having the most pronounced influence. The relationship between thyroid volume, body weight and age in non-goitrous healthy subjects can be described using a formula that allows the calculation of normal thyroid size for a population: Thyroid volume (ml) = 1.97 + 0.21 x bodyweight (kg) + 0.06 x age (years). Cigarette smoking is associated with an approximately 10-fold increase in goitre frequency probably due to a combination of an increased sympathetic stimulation of the thyroid and an iodine deficiency state caused by inhalation of thiocyanate. Although no seasonal alteration in serum TSH level could be demonstrated thyroid volume is 23% higher in the winter than in the summer. Cyclic alterations of thyroid volume possibly related to TSH alterations have been found with a 50% difference between minimum values in the first half and maximum values in the second half of the menstrual cycle. Nonthyroidal illnesses are associated with marked alterations in thyroid volume. Thus, chronic renal disease and acute hepatic disease demonstrate significant increases in thyroid volume although the precise mechanisms have not been clarified. Chronic hepatic disease per se and chronic nonrenal nonhepatic disease does not seem to influence thyroid volume. Chronic alcoholism, however, with or without liver cirrhosis is associated with a marked decrease in thyroid volume and an increase in the amount of fibrosis probably related to a direct toxic effect of alcohol on the thyroid. All these factors should be kept in mind when goitre frequency, goitrogenic action of drugs and goitre treatment effects are evaluated. PMID- 2192838 TI - Monitoring antimicrobial drug resistance in hospital microorganisms. Definition of problems and methods. AB - Hospital infections continue to be an important problem. Changes in patient categories and in the examinations and treatments offered at the hospital, probably constitute the basis upon which new types of infections and new groups of infecting microorganisms continually emerge. The treatment of patients with hospital infections may become complicated by the emergence of drug resistance in the infecting microorganisms. The situation varies between hospitals, and this necessitates a local microbiological monitoring. Prerequisites of a surveillance system in general are described and illustrated by a system monitoring antimicrobial resistance in a Danish county. A specific computer system (software) for the processing of clinical microbiological results was developed by the author to make the local microbiological monitoring possible. Computer assisted analyses for an evaluation of the statistical association of drug resistance traits (phenotype) were also developed. Data on local drug resistance patterns were systematically obtained and analysed in a seven-year study comprising several hundred thousands specimens. Drug resistance genotypes were determined for selected groups of microorganisms (e.g. coagulase-negative staphylococci) in various periods. Data from these studies emphasize that it is important to correlate information about resistance phenotypes of all clinical isolates with the resistance genotypes of selected strains in the monitoring of plasmid mediated resistance and its dissemination. These findings agree well with the results of other but generally less comprehensive studies in the literature. In a study of outpatients treated with a particular antimicrobial (tetracycline), it was shown that this drug selected for plasmid mediated multiple drug resistance in the normal flora of the patients. On the basis of these results and the literature, a general model for the emergence and spread of antimicrobial drug resistance is discussed. Examinations of quantitative relationships between antimicrobial usage and microbial resistance are also reviewed. Analysis of the statistical correlation between various measures of antimicrobial use and the prevalence of microbial resistance in the Danish county corroborates the observation that general changes in prevalence of a particular resistance trait seem to be best explained by taking the mechanisms of co-selection by other antimicrobials into consideration. PMID- 2192839 TI - Zinc gluconate lozenges for common cold. A double-blind clinical trial. AB - In a double-blind clinical trial, a total of 463 volunteers were enrolled in a study designed to compare the effects of zinc gluconate lozenges (4.5 mg zinc) and a placebo for common cold. The tablets were to be taken every 1-1 1/2 waking hours at the first symptoms and for the following days until the common cold was over, but for no longer than 10 days. During the winter months of 1987 and 1988, 145 experienced a common cold and 130 completed the study. For final analysis, 61 patients in the zinc lozenge group and 69 patients in the placebo lozenge group were evaluated. Based on the patients' records the duration and severity of the common cold were compared. No statistically significant differences were found between the patient groups. Two recent studies using a five-time higher zinc dose per lozenge for common cold showed a significant, positive effect, but associated with frequent side-effects, first of all taste distortion. In the present study there was a weak tendency (not statistically significant, p = 0.12) towards more patients in the zinc lozenge group than in the placebo lozenge group reporting side-effects. PMID- 2192840 TI - The presence of an antigen reactive with a human autoantibody in Trichosia pubescens (Diptera: Sciaridae) and its association with certain transcriptionally active regions of the genome. AB - The antigens in HeLa and Trichosia pubescens cells, recognized by sera from patients with rheumatic diseases containing anti-Ku antibodies, were compared by means of immunoprecipitation of labeled cell extracts. The autoantibodies present in the tested sera precipitate at least two polypeptides of approximately Mr = 70,000 and Mr = 80,000 in HeLa cell extracts and a polypeptide of approximately Mr = 72,000 in Trichosia salivary gland cell extracts. The distribution of the insect antigen in chromatin was studied in salivary gland polytene chromosomes by indirect immunofluorescent staining with sera from two different patients. Both sera react with certain transcriptionally active chromosomal sites. The presence of the antigen in polytene chromosomes is strictly dependent on transcription, as no reaction is observed in the same sites before or after gene activation. Other sites, such as the nucleolar organizing region, are very active in transcription but never reacted with the anti-Ku positive sera. These results show that the insect antigen is associated with transcription-related processes of a subset of the chromosomal loci of T. pubescens. The anti-Ku positive sera react with a highly conserved antigen, which may serve a very important and similar role in the cellular metabolism of both insect and mammalian cells. PMID- 2192841 TI - A nucleolar auto-antigen is part of a major chromosomal surface component. AB - Several nucleolar antigens are defined by human autoantibodies. These antigens can therefore be used to follow the fate of nucleolar components through mitosis when this major nuclear structure disintegrates and becomes reassembled in G1 phase. We found that fibrillarin leaves the nucleolus before complete breakdown of this structure and attaches to chromosomes before nuclear envelope breakdown. In mouse, fibrillarin attaches over the chromosomal surface except for the excluded centromeric region. The antigen is transported to the new nucleus via the chromosomes and is last seen on chromosomal surfaces facing the cytoplasm during nuclear envelope reformation. Lamin B reappears on the same chromosomal surfaces before the nucleolar antigen is removed and aggregates for new nucleolar reformation in G1-phase cells. From our observations, we postulate that the antigen acts in concert with other proteins as a nuclear envelope equivalent by forming a protective sheath around the chromosome, that it excludes larger molecules, and helps to separate the chromosomes, in addition to segregation of the ribonucleoprotein (RNP) back to the nucleus for nucleolar reconstruction. We also suggest that the selective retention of these antigens from certain areas on individual chromosomes together with specific lamin B attachment over these chromosomal surfaces allows for a nonrandom positioning of chromosomes in the nucleus. PMID- 2192842 TI - Nucleolin from the multiple nucleoli of amphibian oocyte nuclei. AB - When fixed preparations of newt germinal vesicle (GV) contents are treated with RNase and are then probed with radiolabeled single-stranded DNA in 0.1-2.0 X SSC, the extrachromosomal nucleoli bind the probe non-specifically. DNA/protein blot analysis of proteins from newt GVs shows that gv95, an acidic protein (pI = 5.0) of Mr = 95,000, is the most prominent non-specific DNA-binding protein. Immunocytochemical analysis with affinity purified antibody directed against gv95 shows that it is located in the multiple nucleoli. We used an antibody directed against rat nucleolin to show that newt gv95 and two similar Xenopus GV proteins are the amphibian versions of nucleolin, a nucleolar ribonucleoprotein originally identified in mammalian cells. We show that mAb 3A10, directed against newt histones H1 and H5, labels gv95 on protein immunoblots and the multiple nucleoli in cytological preparations. These results suggest that histone H1 and nucleolin share a cross-reacting epitope. PMID- 2192843 TI - An antigen located in the kinetochore region in metaphase and on polar microtubule ends in the midbody region in anaphase, characterised using a monoclonal antibody. AB - We describe a new component of the kinetochore region of Chinese hamster ovary cells, which was characterised using a monoclonal antibody (mAb). This antigen was localised on the kinetochore regions of purified metaphase chromosomes, but in anaphase it was instead located on the polar microtubules in the midbody region, where they terminate in the stembody. It was not detectable in prophase or interphase cells by immunofluorescence, but was present in the interphase nucleus as shown by immunoblotting after SDS-polyacrylamide gel electrophoresis. The mAb recognised two polypeptides of Mr 140,000 and 155,000. The localisation of this antigen in metaphase on the kinetochore region, where the plus ends of the kinetochore microtubules are temporarily stabilised when they attach, and later in the stembody and midbody where the plus ends of the polar microtubules are stabilised in anaphase and telophase, suggests that it could play a role in stabilising the plus ends of microtubules and thus in the control of microtubule dynamics during mitosis. PMID- 2192844 TI - Regulation of glucose-transporter gene expression in vitro and in vivo. AB - Understanding of the fundamental mechanisms underlying the complex regulation of glucose homeostasis has been dramatically transformed recently by the realization that glucose transport in mammalian tissues is mediated by a family of structurally related but genetically distinct glucose-transporter proteins. The regulatory factors and intracellular signaling pathways that influence expression of the genes encoding these proteins are just being identified. Factors that regulate glucose-transporter gene expression in vitro include oncogenes, growth factors, insulin, oral hypoglycemic agents, vanadate, glucocorticoids, ambient glucose levels, and the state of cellular differentiation. In vivo, glucose transporter gene expression in adipose cells, skeletal muscle, and liver is markedly affected by various altered nutritional and metabolic states. Recent studies have demonstrated that two glucose transporters expressed in the same tissue may be regulated differently in response to the same metabolic perturbation. Furthermore, transporter regulation appears to be tissue specific. These observations lay the groundwork for future studies aimed at unraveling the functional roles of the individual transporter species in different tissues, the molecular processes involved in regulating the expression of these genes, and the impact of dysregulated glucose-transporter gene expression in the pathogenesis of insulin-resistant states such as diabetes. PMID- 2192845 TI - Hybrid insulin receptors. Molecular mechanisms of negative-dominant mutations in receptor-mediated insulin resistance. AB - Certain syndromes of extreme insulin resistance are the result of negative dominant mutations of the insulin receptor. The insulin-receptor heterotetramer appears to be the minimal functional unit for insulin signal transduction probably due to a requirement for intersubunit interactions. The observation that insulin and insulinlike growth factor I receptors can be found in hybrid heterotetramers suggests that insulin receptors can be composed of heterodimers that are the products of separate genes. Such a structure provides a potential molecular mechanism for negative-dominant receptor mutations. PMID- 2192846 TI - Lessons learned from molecular biology of insulin-gene mutations. AB - Studies on naturally occurring and man-made mutations in the insulin gene have provided new insights into insulin biosynthesis, action, and metabolism. Ten families have been identified in which one or more members have single-point mutations in their insulin genes that result in amino acid substitutions within the proinsulin molecule. Six of these cause the secretion of biologically defective insulin molecules due to changes within the A or B chains. Replacing A3 Val with Leu, B24-Phe with Ser, or B25-Phe with Leu results in molecules that have essentially normal immunoreactivity but greatly reduced insulin-receptor binding potency. Individuals with these mutations have a syndrome of mild diabetes or glucose intolerance, which is inherited in an autosomal-dominant mode and is associated with hyperinsulinemia and altered insulin-C-peptide ratios. Although affected individuals are heterozygous and coexpress both normal and abnormal molecules, the elevated circulating insulin consists mainly of the biologically defective form, which accumulates because it fails to be rapidly metabolized via receptor-mediated endocytosis. Four additional families have mutations that are associated with relatively asymptomatic hyperproinsulinemia. A point mutation affecting proinsulin occurs in 3 of the 4 families, leading to replacement of Arg-65 by His, which prevents recognition of the C-peptide-A-chain dibasic cleavage site by the appropriate beta-cell processing protease and results in the circulation of a type II proinsulin intermediate form (des 64, 65 HPI). Members of a fourth family with hyperproinsulinemia have a substitution of B10-His with Asp, resulting in a proinsulin that exhibits markedly altered subcellular sorting behavior.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2192847 TI - Glucose toxicity. AB - Glucose toxicity is a well-established entity that has been shown in animal models of diabetes to contribute to development of insulin resistance and impaired insulin secretion. In type II (non-insulin-dependent) diabetes in humans, a considerable body of evidence has accumulated indicating that a chronic physiological increment in the plasma glucose concentration leads to progressive impairment in insulin secretion and may contribute to insulin resistance as well. The precise biochemical mechanism(s) responsible for the hyperglycemia-induced defect in insulin secretion remains to be defined but may be related to a defect in phosphoinositide metabolism. In animal models of diabetes, development of insulin resistance is related to downregulation of the glucose-transport system, and a similar phenomenon is also likely to occur in humans. In addition, hyperglycemia in humans may lead to a defect in glycogen synthesis. In this respect, humans may be different from rats. In type I (insulin-dependent) diabetic patients who are poorly controlled, insulin resistance is a characteristic feature and can be ameliorated by tight glycemic control, suggesting that hyperglycemia is responsible for the insulin resistance. Evidence also has accumulated to implicate glucose toxicity in the functional impairment in insulin secretion that occurs during the initial presentation of patients with type I diabetes, and this may explain the honeymoon period so commonly observed after the institution of insulin therapy. PMID- 2192848 TI - Insulin and atheroma. 20-yr perspective. AB - Many clinical studies have shown an increased insulin response to oral glucose in patients with ischemia of the heart, lower limbs, or brain. Hyperinsulinemia also occurs in patients with angiographically proved atherosclerosis without ischemia and thus appears to be related to arterial disease and not to be a nonspecific response to tissue injury. Fasting insulin levels and insulin responses to intravenous stimuli, including glucose, tolbutamide, and arginine, are normal, suggesting a gastrointestinal factor may be involved in the increased insulin response to oral glucose. In patients with atherosclerosis, insulin sensitivity appears to be normal or enhanced with respect to both glucose and lipid metabolism. Five population studies have shown that insulin responses to glucose are higher in populations at greater risk of cardiovascular disease. Many of the hyperinsulinemic populations also had upper-body obesity, hypertriglyceridemia, lower high-density lipoprotein (HDL) levels, and hypertension. These prospective studies support an independent association between hyperinsulinemia and ischemic heart disease, although their results differ in detail. Hyperinsulinemia is associated with raised triglyceride and decreased HDL cholesterol levels. Total and low-density lipoprotein (LDL) cholesterol is less closely related to hyperinsulinemia. Upper-body adiposity is associated (in separate studies) with coronary heart disease, diabetes, hyperinsulinemia, and hypertriglyceridemia. Insulin and blood pressure are closely related in both normotensive and hypertensive people. Although obesity and diabetes are often found in hypertensive people, hyperinsulinemia also occurs in nonobese nondiabetic hypertensive people. Thus, hyperinsulinemia is closely associated with a cluster of cardiovascular risk factors, i.e., hypertriglyceridemia, low HDL levels, hypertension, hyperglycemia, and upper-body obesity. There is a possibility that insulin has a role in the sex differences in ischemic heart disease incidence and their absence in diabetes, but additional work is required for its clarification. Long-term treatment with insulin results in lipid-containing lesions and thickening of the arterial wall in experimental animals. Insulin also inhibits regression of diet-induced experimental atherosclerosis, and insulin deficiency inhibits the development of arterial lesions. Insulin stimulates lipid synthesis in arterial tissue; the effect of insulin is influenced by hemodynamic factors and may be localized to certain parts of the artery. In physiological concentrations, insulin stimulates proliferation and migration of cultured arterial smooth muscle cells but has no effort on endothelial cells cultured from large vessels. Insulin also stimulates cholesterol synthesis and LDL binding in both arterial smooth muscle cells and monocyte macrophages.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2192849 TI - Physiology and pathophysiology of insulin secretion. AB - Mechanisms by which various classes of extracellular signals regulate insulin secretion are discussed regarding their cellular and molecular actions. Under physiological circumstances, the small postprandial changes in plasma glucose concentrations (approximately 4.4-6.6 mM) primarily serve as a conditioned modifier of insulin secretion and dramatically alter the responsiveness of islets to a combination of neurohormonal agonists. These agonists have two functions. Cholecystokinin (CCK) and acetylcholine activate the hydrolysis of polyphosphoinositides, and gastric inhibitory polypeptide (GIP) and glucagonlike peptide 1 activate adenylate cyclase. These two functional classes of neurohumoral agonists act synergistically to enhance insulin secretion when plasma glucose is greater than 6.0 mM but not when it is less than or equal to 4 mM. On the other hand, an increase in plasma glucose concentration to 8-10 mM induces an increase in insulin secretory rate in the absence of any of the neurohormonal agonists. Remarkably, high glucose leads to an increase in the same intracellular signals, as does a combination of acetylcholine and GIP. On the basis of these data, a model of how insulin secretion is regulated under physiological circumstances is proposed. This model emphasizes that the regulation of insulin secretion occurs in three stages: cephalic, early enteric, and later enteric. In this view, the crucial event occurring during the first two phases is the agonist-induced, translocation of protein kinase C (PKC) to the plasma membrane under conditions in which an increase in Ca2+ influx does not occur. PKC is now in a cellular location and a Ca2(+)-sensitive conformation such that an increase in Ca2+ influx rate occurring during the third phase leads to its immediate activation and an enhanced rate of insulin secretion. Furthermore, under physiological circumstances, an optimal insulin secretory response is dependent on a correct temporal pattern of signals arising from neural and enteric sources. If this pattern is deranged, an abnormal pattern of insulin secretion is observed. An important new insight is provided by the observation that agonists (e.g., CCK or acetylcholine) that act to stimulate the hydrolysis of phosphatidylinositides, when acting for a short period (10-20 min), induce an enhanced responsiveness of islets to glucose, i.e., proemial sensitization. However, when acting unopposed for several hours, these agonists will induce a time-dependent suppression of responsiveness to glucose and other agonists. The latter observation implies that optimal insulin secretion is dependent on periodic rather than a continuous exposure to the correct pattern of extracellular signals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2192850 TI - Combination insulin-sulfonylurea therapy. AB - Combination sulfonylurea-insulin therapy for patients with diabetes mellitus has been evaluated by numerous investigators with various experimental designs. Much of the data are conflicting, and clear conclusions do not seem justified. Insulin sulfonylurea therapy is probably not clinically useful in most patients with insulin-dependent diabetes mellitus. Most non-insulin-dependent diabetic (NIDDM) patients are also unlikely to have meaningful improvement in glycemic regulation on insulin-sulfonylurea therapy. A subset of NIDDM patients who are mildly to moderately obese, have adequate endogenous insulin secretory reserve, and are in poor glycemic regulation (fasting plasma glucose greater than 11 mM and/or HbA1 greater than 10%), despite twice-daily insulin administration of greater than 70 U/day, may show significant improvement of glycemic regulation and/or decreases in insulin daily dose on insulin-sulfonylurea therapy. The mechanisms by which insulin-sulfonylurea therapy improves glycemic regulation and decreases insulin requirements involve an increase in endogenous insulin secretion and possibly some extrapancreatic actions of the sulfonylureas on muscle and liver. PMID- 2192851 TI - Evening insulin strategy. AB - A series of regimens based on intermediate-acting insulin given in the evening have been proposed as an alternative to conventional insulin therapy for non insulin-dependent diabetes mellitus (NIDDM). This concept dates back to the earliest use of sustained-action insulin and has a rationale strengthened by recent physiological insights. Specifically, the predominance of fasting over postprandial hypoglycemia and occurrence of the dawn phenomenon in NIDDM argue for carefully timed overnight delivery of insulin. High nocturnal concentrations of free fatty acids in NIDDM may contribute to hepatic insensitivity to insulin and fasting hyperglycemia and can be suppressed by evening insulin. Although several clinical studies suggest that evening insulin regimens are safe and effective, their role in clinical practice is not yet established. Further study of this approach may clarify not only its proper use but also the best use of conventional strategies. PMID- 2192852 TI - Combination therapy with insulin and sulfonylureas for type II diabetes. AB - Combination therapy for type II (non-insulin-dependent) diabetes mellitus with insulin and sulfonylureas has been a topic of interest since the latter were introduced to clinical use. In recent years, improved understanding of potential complications associated with hyperinsulinemia has led to resurgent interest in alternatives to insulin monotherapy for patients who have failed on a regimen of diet and sulfonylureas. A plethora of clinical trials have reported on the efficacy of oral hypoglycemic agents in limiting insulin requirements while achieving glycemic control in this subset of diabetic patients. However, few studies have been appropriate in both design and duration to provide convincing results. The randomized placebo-controlled double-blind trials that have used a parallel design and study periods of up to 1 yr have uniformly investigated second-generation sulfonylureas and yielded the most reliable information. In all instances, the combination regimen achieved reduction in insulin requirement with varying evidence of a pancreatic effect as the responsible mechanism. This treatment modality is becoming more widely accepted in the effort to achieve optimal glycemic control with minimum risk to the patient. PMID- 2192853 TI - Diabetes mellitus in the Pima Indians: incidence, risk factors and pathogenesis. PMID- 2192854 TI - Type II diabetes and its complications in Mexican Americans. AB - The prevalence and incidence of type II diabetes are substantially higher in Mexican Americans than in non-Hispanic whites. This, combined with its earlier age of onset and the younger age structure of the Mexican American population, makes diabetes a major public health problem in this ethnic group and one which to a greater extent than in non-Hispanics strikes people in the prime of life. Both genetic and environmental factors undoubtedly contribute to this epidemic. The environmental factors would appear to be those commonly associated with the phenomenon of "modernization" or "westernization", namely, dietary change and adoption of sedentary lifestyles. As such, they are potentially modifiable and amenable to clinical and public health action. There is as yet no proof from clinical trials that modification of any or all of these environmental factors will in fact prevent diabetes. When clinical trials are performed, high-risk populations such as Mexican Americans should be considered as potential target populations, because of both the public health relevance and the lower sample size requirements in such populations. Further advances in identifying genetic susceptibles would also facilitate the design and execution of such trials. The increased risk of microvascular complications in Mexican American diabetics puts this population in "double jeopardy", i.e., they have a greater risk of acquiring diabetes in the first instance, and, having acquired it, they have a greater risk of suffering from its complications. It is still not clear whether the increased risk of complications in this ethnic group stems from an intrinsically more severe biological process or barriers to adequate medical care and/or poor compliance. Prospective data currently being gathered should help to resolve this issue. Assuming that medical care plays a role, a major opportunity--and challenge--exists to reduce substantially the morbidity, mortality, and economic burden associated with type II diabetes and its complications in the Mexican American population. PMID- 2192855 TI - Hyperlipidemia in diabetes mellitus. PMID- 2192856 TI - [The therapy and prevention of esophageal variceal bleeding]. PMID- 2192857 TI - [Psychometric tests in HIV infection and AIDS]. PMID- 2192858 TI - Mucoepidermoid carcinoma of the esophagus: report of two cases and review of the literature. AB - The clinicopathological manifestation of mucoepidermoid carcinoma of the esophagus are reported in two cases. Barium swallow and endoscopy revealed infiltrating and constricting appearances. The tumors were grossly indurated, with or without ulceration. Histologically, the tumors were composed of a mixture of glandular cells which contained signet ring cells and squamous cells. In two cases, the tumor cells invaded into the adventitia, with lymph node metastasis. Two patients died of wide-spread metastasis within 1 year after operation. Our results and previous reports suggest that mucoepidermoid carcinoma of the esophagus is extremely aggressive and has a poor prognosis. PMID- 2192859 TI - Endoscopic injection hemostasis of colonic diverticular bleeding: a case report. PMID- 2192860 TI - Structure of donor side components in photosystem II predicted by computer modelling. AB - Thirty-one and eleven sequences for the photosystem II reaction centre proteins D1 and D2 respectively, were compared to identify conserved single amino acid residues and regions in the sequences. Both proteins are highly conserved. One important difference is that the lumenal parts of the D1 protein are more conserved than the corresponding parts in the D2 protein. The three-dimensional structures around the electron donors tyrosineZ and tyrosineD on the oxidizing side of photosystem II have been predicted by computer modelling using the photosynthetic reaction centre from purple bacteria as a framework. In the model the tyrosines occupy two cavities close to the lumenal surface of the membrane. They are symmetrically arranged around the primary donor P680 and the distances between the centre of the tyrosines and the closest Mg ion in P680 are around 14 A. Both tyrosineZ and tyrosineD are suggested to form a hydrogen bond with histidine 190 from the loop connecting helices C and D in the D1 and D2 proteins, respectively. The Mn cluster in the oxygen evolving complex has been localized by using known and estimated distances from the tyrosine radicals. It is suggested that a binding region for the Mn cluster is constituted by the lumenal ends of helices A and B and the loop connecting them in the D1 protein. This part of the D1 protein contains a large number of strictly conserved carboxylic acid residues and histidines which could participate in the Mn binding. There is little probability that the Mn cluster binds on the lumenal surface of the D2 protein. PMID- 2192861 TI - Topography of intermediates in transcription initiation of E.coli. AB - Three characteristic footprinting patterns resulted from probing the Escherichia coli RNA polymerase T7 A1 promoter complex by hydroxyl radicals in the temperature range between 4 degrees C and 37 degrees C. These were attributed to the closed complex, the intermediate complex and the open complex. In the closed complex, the RNA polymerase protects the DNA only at one side over five helical turns. In the intermediate complex, the range of the protected area is extended further downstream by two helical turns. This region of the DNA helix is fully protected, indicating that the RNA polymerase wraps around the DNA between base positions -13 and +20. In the open complex, a stretch between base positions -7 and +2, which was fully protected in the intermediate complex, becomes accessible towards hydroxyl radicals but only in the codogenic strand, indicating that the DNA strands are unwound. Our data suggest that only the DNA downstream of the promoter is involved in this unwinding process. PMID- 2192862 TI - ProOmpA contains secondary and tertiary structure prior to translocation and is shielded from aggregation by association with SecB protein. AB - Escherichia coli protein export involves cytosolic components termed molecular chaperones which function to stabilize precursors for membrane translocation. It has been suggested that chaperones maintain precursor proteins in a loosely folded state. We now demonstrate that purified proOmpA in its translocation component conformation contains both secondary and tertiary structure as analyzed by circular dichroism and intrinsic tryptophan fluorescence. Association with one molecular chaperone, SecB, subtly modulates the conformation of proOmpA and stabilizes it by inhibiting aggregation, permitting its translocation across inverted E.coli inner membrane vesicles. These results suggest that translocation competence does not simply result from the maintenance of an unfolded state and that molecular chaperones can stabilize precursor proteins by inhibiting their oligomerization. PMID- 2192863 TI - The Escherichia coli heat shock proteins GroEL and GroES modulate the folding of the beta-lactamase precursor. AB - One of the fundamental problems in biochemistry is the role of accessory proteins in the process of protein folding. The Escherichia coli heat shock protein complex GroEL/ES has been suggested to be a 'chaperonin' and be involved in both oligomer assembly as well as protein transport through the membrane. We show here that the folding of the purified precursor of beta-lactamase is inhibited by purified GroEL or the GroEL/ES complex with a stoichiometry of one particle per molecule of pre-beta-lactamase. Purified GroES alone has no effect on folding. After Mg2+ ATP addition folding resumes and the yield of active enzyme is higher than in the absence of GroEL or GroEL/ES. Unexpectedly, GroEL or GroEL/ES, when added to folded pre-beta-lactamase, lead to an apparent net 'unfolding', probably to a collapsed state of the protein, which can be reversed by the addition of Mg2+ ATP. The reversible and Mg2+ ATP-dependent association of GroEL/ES with non native proteins might explain its postulated role in both protein transport and oligomer assembly. PMID- 2192865 TI - Biochemical markers of bone turnover for the clinical assessment of metabolic bone disease. AB - There is not yet an ideal marker of bone formation, but circulating BGP is the most satisfactory at present. New developments include the use of sheep BGP64 and human BGP85 as an immunogen and monoclonal antibodies, which may recognize fragments of BGP released during resorption. The specific measurement of bone alkaline phosphatase and the assay of procollagen fragments and of other noncollagenous bone-related proteins will allow a more precise assessment of the complex osteoblastic functions in normal and pathologic conditions. Finding a sensitive and specific marker of resorption is a challenge because all constituents of bone matrix are likely to be degraded into minute peptides during osteoclastic bone resorption. The measurement of pyridinium crosslinks and possibly of tartrate-resistant acid phosphate by a bone-specific monoclonal antibody are the most tangible improvements in this area. These markers need to be validated by comparison with data obtained by direct measurement of bone turnover on iliac crest biopsy. It should be remembered, however, that circulating markers reflect the overall activity of the whole skeleton, including the cortical, subcortical, and trabecular envelopes, which have different remodeling rates in normal and abnormal states. A circulating marker will not detect a specific defect of the cellular activity of one compartment of bone if the summated turnover of the skeleton is unchanged. Conversely, bone histomorphometry is limited to a small area of the trabecular envelope but allows detection of a specific defect at the cellular level. These differences should be kept in mind, as there is growing evidence that, for example, bone mass and bone turnover of osteoporotic patients before and during treatment vary in different appendicular/axial and cortical/trabecular compartments. Finally, a single marker might be valuable in some diseases and not in others (such as serum BGP in Paget's disease of bone). Despite these difficulties, significant advances have been made in the last few years in the bone marker field. In the future, the development of a battery of several bone-specific markers that indicate various aspects of the complex mechanisms of bone formation, resorption, and mineralization is likely to provide new tools for the diagnosis and management of bone diseases. PMID- 2192864 TI - An essential Saccharomyces cerevisiae single-stranded DNA binding protein is homologous to the large subunit of human RP-A. AB - Single-stranded DNA binding proteins (SSBs) are known to play a role in DNA replication and recombination in prokaryotes. An SSB was previously purified from the yeast Saccharomyces cerevisiae. This SSB stimulated the activity of a cognate strand exchange protein (SEP1) in vitro suggesting a role in recombination. We have cloned and functionally analyzed the gene encoding this protein. DNA sequencing of the cloned DNA revealed a 621 amino acid open reading frame with a coding potential for a Mr 70,269 polypeptide. Highly significant amino acid homology was detected between this S.cerevisiae gene and the Mr 70,000 subunit polypeptide of human RP-A, a cellular protein essential for SV40 DNA replication in vitro. Therefore, we named the S.cerevisiae gene RPA1. RPA1 encodes an essential function in this organism as shown by tetrad analysis of heterozygous insertion mutants and is continuously required for mitotic growth. Cells lacking RPA1 accumulate as multiply budded cells with a single nucleus suggesting a defect in DNA replication. PMID- 2192866 TI - Paget's disease of bone. AB - Paget's disease of bone is defined as a process of increased bone remodeling; the primary event is increased resorption (osteoclastic activity) followed by subsequent reactive bone formation (osteoblastic activity). It is usually asymmetric and may be asymptomatic. The etiology is unknown, but recent evidence appears to support the theory that a virus is an important etiologic factor. It may present with a wide variation in the clinical and radiographic picture. The most frequent sites of involvement include the spine, femora, cranium, pelvis, and sternum. The most common complaints are pain, skeletal deformity, and change in skin temperature. Pathologic fractures may be the presenting manifestations or complications in a patient with known Paget's disease. They occur most frequently in the long weight-bearing bones of the lower extremities such as the femoral neck and subtrochanteric and tibial regions. The two major therapeutic agents available for treatment are calcitonins (porcine, salmon, or human) and diphosphonates. The aim of such therapy is to control the metabolic activity of the disease, to normalize the biochemical parameters, and to improve the symptoms. Fortunately, tumors are rare; early diagnosis may give rise to more effective palliation, if not a significant cure rate. PMID- 2192867 TI - Bone disease in primary hyperparathyroidism. AB - The classic bone disease of primary hyperparathyroidism, osteitis fibrosa cystica, was characterized by subperiosteal bone resorption, osteopenia, and "brown tumors." Since the description of this skeletal disorder, the clinical profile of primary hyperparathyroidism has evolved markedly. The disease today is often characterized by no more than asymptomatic hypercalcemia, and severe bone disease is a distinct rarity. However, as we have endeavored to show in this article, newer and more sensitive techniques show significant evidence of the effect of excess parathyroid hormone on the skeleton. Bone density as measured by photon absorptiometry and bone histomorphometry show a deficit of cortical bone and a preservation or increase in cancellous bone elements in mild primary hyperparathyroidism with no clinical evidence of skeletal disease. Important questions exist as to the therapeutic implications of these data. Does the presence of parathyroid hormone effect on sophisticated testing portend the development of clinical bone disease? Should these data be used as a rationale for surgical intervention in patients who might otherwise be followed conservatively with mild primary hyperparathyroidism? The answers to these questions must await further data collection and study. PMID- 2192868 TI - Effects of thyroid hormones on bone and mineral metabolism. AB - Because of pronounced symptoms and early detection, severe hyperthyroidism is usually treated before skeletal symptoms are evident. However, previous hyperthyroidism may involve a risk of later postmenopausal or senile osteoporosis, since some of the bone loss apparently is irreversible. Borderline hyperthyroidism in clinically euthyroid patients may induce accelerated bone loss and thereby increase the risk of low-energy fractures. Moreover, it is unknown whether interindividual differences exist in skeletal sensitivity to circulating thyroid hormones and thereby in the rate of bone loss. From these considerations it appears that disturbed thyroid function may be involved in the pathogenesis of osteoporosis, one of the major health problems in the western hemisphere. PMID- 2192869 TI - Renal osteodystrophy. AB - Renal osteodystrophy is a complex disorder which can be divided into five distinct bone histologic subtypes: mild bone disease, hyperparathyroid bone disease, mixed bone disease, osteomalacia, and low-turnover bone disease. Hyperparathyroidism develops in renal failure due to two principal abnormalities: 1,25(OH)2D3 deficiency and hyperphosphatemia. Treatment of these problems is important in order to prevent hyperparathyroidism. Most cases of osteomalacia, mixed bone disease, and low-turnover bone disease are influenced by aluminum status and parathyroid hormone. Aluminum-associated bone disease can be treated with termination of aluminum exposure and/or deferoxamine therapy. Numerous diagnostic pitfalls exist in the evaluation of renal osteodystrophy, and the bone biopsy is extremely important to avoid these problems and plan proper therapy. PMID- 2192870 TI - Corticosteroid-induced osteoporosis. AB - Glucocorticoid-induced bone loss has been recognized for almost 50 years, yet it remains an important medical problem and a common cause of fracturing. Loss of skeletal mass may occur early in the course of glucocorticoid therapy and appears to be related to the cumulative dose of steroid, as well as to the usual risk factors for osteoporosis. The pathophysiology of this disorder is poorly understood, but available information suggests that glucocorticoids exert direct and indirect actions on bone and calcium homeostasis that may contribute to osteopenia. Direct effects appear to occur soon after the initiation of glucocorticoid therapy and include (1) suppression of intestinal calcium absorption, (2) decreased renal tubular calcium resorption with increased urinary calcium excretion, and (3) suppressed osteoblast function and decreased bone formation. Ultimately, renal and intestinal losses of calcium result in the development of secondary hyperparathyroidism, which, in concert with stimulation of parathyroid secretion and an increased sensitivity of bone cells to PTH, produces an increase in bone resorption and bone turnover. Although effective forms of prevention and treatment have not been identified, available information provides a rationale for the use of calcium supplements, maintenance of vitamin D nutrition, and the use of agents that suppress bone resorption and bone turnover. The use of sodium fluoride to stimulate bone formation has not been fully tested in this condition and it remains an investigational agent. Although recent advances in our understanding of the glucocorticoid receptor are likely to lead us to new therapeutic approaches, present methods of prevention and treatment have not been adequately evaluated and await prospective study. PMID- 2192871 TI - Lipoprotein physiology and its relationship to atherogenesis. AB - The major plasma lipids, cholesterol, triglycerides, and phospholipids are transported as components of macromolecular complexes called lipoproteins. The major lipoprotein classes include the chylomicrons, which transport dietary lipids to the peripheral tissues and the liver; very low density and low density lipoproteins, which transport endogenously synthesized lipids from the liver to peripheral tissues; and high density lipoproteins, which appear to facilitate the reverse transport of cholesterol from peripheral tissues to the liver. The rates of synthesis and catabolism of the major lipoprotein classes are regulated, to a large degree, by one or more proteins, called apoproteins, that reside on the surface of the lipoproteins. This article describes normal lipoprotein metabolism and includes discussions of the role of abnormalities in lipoprotein transport in the atherogenic process. PMID- 2192872 TI - Inherited disorders of lipid transport. AB - The number of well-described discrete disorders of lipid transport is increasing, and the classification of the disorders also is changing, from one based on altered concentrations of classes of lipoproteins, to one based on improved understanding of the genetics of the disorders and of lipoprotein biochemistry and physiology. Many disorders are now traceable to structural defects in or the absence of key proteins such as apolipoproteins, enzymes, lipid transfer proteins, and cellular receptors. PMID- 2192873 TI - Acquired hyperlipidemia (secondary dyslipoproteinemias). AB - Acquired hyperlipidemia (secondary dyslipoproteinemias) results from underlying disorders that lead to alterations in plasma lipid and lipoprotein metabolism. Secondary dyslipoproteinemias may mimic primary forms of hyperlipidemia and can have similar consequences. They may result in increased predisposition to premature atherosclerosis or, when associated with marked hypertriglyceridemia, may lead to the development of pancreatitis and other features of the chylomicronemia syndrome. Diabetes mellitus and use of drugs such as diuretics, beta blockers, and estrogens are commonly encountered causes of secondary dyslipoproteinemia. Other conditions leading to acquired hyperlipidemia include hypothyroidism, renal failure, nephrotic syndrome, alcohol usage, and some rare endocrine and metabolic disorders. When secondary and familial forms of hypertriglyceridemia coexist, triglyceride removal mechanisms may be saturated and marked hypertriglyceridemia with fasting chylomicronemia might ensue. Treatment of the underlying condition, when possible, or discontinuation of the offending drugs usually leads to an improvement in the hyperlipidemia. Specific lipid-lowering therapy may be required in certain circumstances. PMID- 2192874 TI - Does lowering serum cholesterol levels lower coronary heart disease risk? AB - Many lines of evidence converge toward the conclusion that low-density lipoprotein cholesterol (LDLC) is indeed a causal factor in the genesis of CHD. These range from animal studies, pathology studies, inborn errors of metabolism, clinical observations, and the existence of plausible biologic mechanisms, to the vast body of epidemiologic evidence. Observations of the association of LDLC with CHD hold between different populations, in the same population at different times, and to studies of individuals within populations. Finally, the clinical trials of cholesterol lowering, together with regression studies in animals and angiographic studies in humans, provide compelling evidence that the progress of atherosclerosis can be halted and the clinical sequelae can be reduced. The newly available results from more recent intervention studies have reinforced the validity of this conclusion. The intervention studies reduced the CHD incidence rate by approximately 2% for every 1% reduction in total cholesterol (TC) even though the studies were of relatively short duration (typically 5 years). More prolonged exposure to lower TC levels can be expected to yield even greater ultimate benefit. The benefit is most clearcut for men at highest risk. The combined data indicate that both fatal and nonfatal CHD can be reduced. More data on the extremes of age, on subjects with moderate elevations of TC, and on women would be valuable, but it is reasonable to proceed with advice to the general population aimed at reducing average cholesterol levels, and also to identify and treat those at high risk. There is good reason to expect that these measures will further reduce MI events and in all likelihood also MI deaths. Whether they will also reduce overall mortality is at present a moot point; however, a reduction in the burden of nonfatal MI would in itself be a very desirable objective. PMID- 2192875 TI - Role of circulating high-density lipoprotein and triglycerides in coronary artery disease: risk and prevention. AB - A substantial body of evidence suggests that circulating levels of high-density lipoprotein (HDL) and certain triglyceride-carrying lipoproteins may, like low density lipoprotein (LDL), be important risk factors in the development of atherosclerotic coronary artery disease (CAD). Furthermore, both low HDL cholesterol and high triglyceride levels are frequently associated with other CAD risk factors, whose correction, often by hygienic means, may reduce CAD risk without fear of adverse side effects. However, the available evidence is not yet sufficiently coherent and compelling to justify guidelines (analogous to those for LDL cholesterol) for specific pharmacologic treatment of low plasma HDL cholesterol or moderately elevated plasma triglyceride levels to prevent CAD. PMID- 2192876 TI - Detection and evaluation of dyslipoproteinemia. AB - Screening for dyslipoproteinemias should be undertaken in all individuals older than 20 years of age at least once every 5 years. The initial screening, as recommended by the Adult Treatment Guidelines Panel of the National Cholesterol Education Program, is to determine the concentration of total blood cholesterol. This initial determination can be made on blood obtained in the nonfasting state. Further evaluation of the patient's lipoprotein concentrations is dependent upon the presence of other cardiovascular risk factors. in the absence of definite coronary heart disease, hypertension, diabetes mellitus, a family history of coronary artery disease, cigarette smoking, or severe obesity, the patient with a total blood cholesterol concentration less than 200 mg/dL requires no specific instruction and should have a repeated screening performed within 5 years. Patients with blood cholesterol concentrations greater than 200 mg/dL should have their lipoprotein profiles determined if they have atherosclerotic cardiovascular disease or two other cardiovascular disease risk factors. The lipoprotein profile includes the determination of fasting cholesterol and triglyceride and HDL cholesterol concentrations. From these values, the LDL cholesterol concentration can be calculated. This LDL cholesterol concentration is central in selecting the appropriate therapy. HDL cholesterol concentrations may be useful in evaluating patients with ischemic heart disease. Concentrations of HDL cholesterol less than 35 mg/dL are associated with increased risk for coronary artery disease. Although there is currently no convincing evidence that support the specific treatment of depressed HDL cholesterol concentrations, therapy directed to modulating lipoprotein metabolism in patients with heart disease and low HDL concentrations may be of benefit. Patients with recurrent abdominal pain, pancreatitis, and eruptive xanthomatosis frequently have fasting hypertriglyceridemia concentrations exceeding 1000 mg/dL. These patients should be identified in order to effectively reduce their triglyceride concentrations, which can prevent these complications. PMID- 2192877 TI - Drug treatment of dyslipoproteinemia. AB - The bile-acid sequestrants, nicotinic acid and lovastatin, are the most effective drugs for lowering LDL-cholesterol. Nicotinic acid and gemfibrozil are more effective for lowering triglycerides and increasing HDL. Important considerations for proper selection of drugs in the treatment of the various dyslipoproteinemias are presented. Currently available drugs now permit effective control of blood lipid and lipoprotein levels. PMID- 2192878 TI - Dyslipoproteinemia and diabetes. AB - Lipoprotein changes in diabetes are discussed from both a pathophysiologic and clinical viewpoint. Though differences in concentrations are often small and vary according to the type of diabetes, other changes in lipoprotein metabolism are presented. The interrelationships between diabetes, insulin, and heart disease are also discussed, with the central role of insulin being stressed. Finally, the clinical management of lipid disorders in diabetes is addressed. PMID- 2192879 TI - Dyslipoproteinemia in women. Special considerations. AB - Heart disease is the number one cause of death in women, as it is in men; risk factors include high cholesterol, high triglycerides, low HDL-C, diabetes, hypertension, and cigarette smoking. Most of these factors are alterable. The lipoprotein profile of a woman undergoes many changes during her lifetime because of the effects of endogenous hormones at pregnancy, the administration of oral contraceptives, and estrogen replacement at the menopause. Endogenous estrogen reduces the risk of heart disease in women as does unopposed estrogen replacement in the menopause. Oral contraceptives, on the other hand, can increase risk depending on the dose prescribed. Careful attention to a woman's native lipid profile, as well as to the impact of administered hormones on her lipids, is important. It is the responsibility of the physician to help patients achieve and maintain the least atherogenic lipid profile possible as well as to identify and reduce other cardiovascular risk factors. PMID- 2192880 TI - Screening, diagnosis, and management of dyslipoproteinemia in children. AB - The authors provide an extensive and comprehensive review of dyslipoproteinemia in children. An effective program for CVD reduction in this population will include an accessible screening program to identify high-risk children, high quality measurements of TC and LP-C, careful follow-up of screening results with multiple measurement to classify risk status and diagnose primary dyslipidemia, a key role for family and education, and consistent and long-term follow-up for diet and drug adherence, efficacy, and safety. PMID- 2192881 TI - Dyslipoproteinemia in the elderly. Special considerations. AB - Reduction in blood cholesterol levels has the potential for reducing morbidity and mortality from CHD in elderly adults. Although definitive trials have not been undertaken, the guidelines of the Adult Treatment Panel of the NCEP provide the basis for diagnosis and treatment of the disease. Dietary therapy should be the principal approach in the elderly. A balanced diet low in saturated fats and high in fruits, vegetables, and grains should both reduce cholesterol and confer other healthful benefits. The potential for improvement in this population is large, as is the challenge to the medical community. PMID- 2192882 TI - Mutagenesis in Escherichia coli lacking catalase. AB - Escherichia coli K-12 strains completely lacking catalase activity due to mutations in katG, katE, and katF genes were constructed in order to assess the role of hydrogen peroxide in mutagenesis. Mutagenesis was monitored by selecting forward mutations to L-arabinose resistance. Lethality was measured at experimental conditions equivalent to those of the mutant yield by using a mixed culture of pairs of isogenic strains distinguished by their differential nutritional requirements. Deficiency in katG, katE, and katF genes leads to an enhanced spontaneous mutation rate as well as an enhanced sensitivity to both the lethal and mutagenic effects of hydrogen peroxide or an H2O2-generating mixture of compounds, such as coffee. To compare further the responses of the catalase deficient bacteria to those of catalase-proficient counterparts, other genotoxins were analyzed. Both catalase-deficient and catalase-proficient strains were equally mutated by MMS, 4-NQO, and ultraviolet light. It is concluded that the bacterial strains and the mutagenicity tests described in the paper represent a useful tool to study the role of H2O2 in mutagenesis. PMID- 2192883 TI - Assay-specific genotoxicity of N-nitrosodibenzylamine to the rat liver in vivo. AB - N-Nitrosodibenzylamine (NDBzA) is mutagenic to Salmonella typhimurium and induces DNA strand breaks in isolated rat hepatocytes, yet it is reported to be non carcinogenic to the rat. Here we report that it is inactive in both the rat and mouse bone marrow micronucleus assays and in a rat liver autoradiographic assay for unscheduled DNA synthesis. It is, however, clearly active as a micronucleus inducing agent and mitogen in the rat liver and is capable of inducing single strand breaks in the DNA of rat liver. The origin and implications of this curious conflict of in vivo genotoxicity data are discussed. Irrespective of that discussion, it is concluded that NDBzA is genotoxic to the rat liver in vivo. PMID- 2192884 TI - Nodular form of intra-abdominal panniculitis: sonographic features. AB - Sonography of a patient with acute upper abdominal pain demonstrated an encapsulated hyperechoic mass which indented the stomach. Fine-needle biopsy produced atypical cells; the diagnosis of nodular intra-abdominal panniculitis was made at surgery. Sonography probably has a role in the detection and follow up of this benign lesion. PMID- 2192885 TI - Comparison of Duplex sonography and color Doppler imaging in renal allograft evaluation: a prospective study. AB - A prospective study compared the diagnostic capability of quantitative Duplex sonography (DS) and color Doppler imaging (CDI) in 49 consecutive patients with 50 renal allografts. Sixty five DS examinations and 65 CDI examinations were performed by two independent investigators on two different machines on the same day. The resistive index (RI) was calculated and the color flow of renal arteries was observed up to the arcuate arteries. There was good correlation of RI values obtained by DS and CDI at all vascular sites. Thirty one allografts were functioning stably and 19 were in a state of dysfunction, defined by histology (n = 17). Forty allografts presented with a RI less than 0.9 and normal color flow. All five allografts with a pathologic RI greater than or equal to 0.9 showed abnormal color flow (missing flow in arcuate and/or interlobar arteries). Five allografts had a RI less than 0.9 but abnormal color flow, possibly due to atrial fibrillation, hypertension, heart failure or a combination of these. A normal color flow pattern excludes severe vascular compromise to the allograft. In addition, CDI revealed three biopsy-related vascular lesions; two of them had been missed by DS. PMID- 2192886 TI - The mid-trimester placenta previa: a prospective follow-up. AB - One hundred and fifty-six mid-trimester sonograms were performed at our prenatal diagnostic unit. Twenty women were found to have a low-lying placenta or placenta previa and were followed by serial ultrasound examinations to observe changes in placental position. Eighty percent of women, i.e., 16/20, with a low-lying placenta had converted to normal implantation by the time of delivery. Most of the conversions had taken place at approx. 34 weeks of gestation. The patients with mid-trimester low-lying placenta had an increased risk of third-trimester bleeding, abruptio placentae and cesarean sections. The infants were also at risk of premature delivery. Patients with mid-trimester low-lying or placenta previa should be followed by ultrasound to monitor delivery. PMID- 2192887 TI - Current methods of digital imaging in conventional X-ray diagnostics. PMID- 2192888 TI - Sensory evoked potentials in Creutzfeldt-Jakob disease. AB - Eight patients presenting with intermediate or terminal evolution of Creutzfeldt Jakob disease (CJD) were investigated by means of evoked potentials. Fifteen age matched healthy subjects served as controls. The 8 patients had well-recognizable but simplified flash evoked potentials (FEPs) consisting of P1 and N2 waves followed by a single late positive (P2) deflection. Enlarged FEPs were found in 2 of the 8 patients. The somatosensory central conduction time was normal in 3 of 5 patients, and it resulted in upper normal limits or was moderately slowed in 2 patients. No enlarged somatosensory scalp potentials were recorded. Cortical somatosensory responses were characterized by an unrecognizable (4 patients) or delayed (2 patients) N33 wave. Brainstem auditory evoked responses, recorded in 6 patients, were normal. In CJD very important functional impairment of the sensory cortical areas is associated with absent or mild dysfunction of the subcortical sensory pathways. PMID- 2192889 TI - Sixty years of clinical electroencephalography. AB - As a result of painstaking studies carried out over a period of almost 30 years, the German neurologist and psychiatrist Hans Berger, of Jena, published the first paper on the human electroencephalogram (Uber das Elektrenkephalogramm des Menschen') in 1929. Clinical electroencephalography, which reached a zenith in the 1950s and 1960s, increased the range of diagnostic techniques available for a series of brain diseases and revolutionized the study of epilepsy. Today, conventional electroencephalography no longer yields startling scientific discoveries. Nor can it complete with computer tomography and magnetic resonance imaging, in the diagnosis of structural disorders of the brain. In spite of this, the scope of its uses continues to increase and it remains an indispensable instrument of neurophysiological diagnosis, especially in its capacity as a 'seismograph' of the brain. The trend that is apparent throughout the world to cut back clinical electroencephalographic units in favor of other neurophysiological investigative techniques is both unjustified and dangerous. If it continues, it will inevitably lead to a decline in epileptology, which is an essential part of the work of many different medical specialists both in practice and in hospitals. PMID- 2192890 TI - Role of oxygen in regulation of glycolysis and lactate production in human skeletal muscle. PMID- 2192891 TI - Physiological adaptations to weightlessness: effects on exercise and work performance. PMID- 2192892 TI - Biomechanical response of bone to weightlessness. PMID- 2192893 TI - Bioelectric impedance for body composition. PMID- 2192894 TI - Human body segment inertia parameters: a survey and status report. PMID- 2192895 TI - Physical activity and coronary heart disease risk factors during childhood and adolescence. PMID- 2192896 TI - Measuring the cardiovascular endurance of persons with mental retardation: a critical review. PMID- 2192897 TI - Prevention of ligament injuries to the knee. AB - Disruption of the ligamentous structures of the knee are commonly seen in competitive sports. Factors affecting the rate of injury include the sport, the participant, conditioning and technique, the level of competition, rules enforcement, the type of playing surface, and footwear. The role of prophylactic and functional bracing is controversial. Currently, prophylactic bracing has not been shown, conclusively, to be protective. Functional braces appear to have a capacity to provide some protective effect. PMID- 2192898 TI - Determinants of exercise behavior. PMID- 2192899 TI - Moral development in sport. PMID- 2192900 TI - Application of epidemiological methodology to sports and exercise science research. PMID- 2192901 TI - Energy substrate utilization during exercise in extreme environments. PMID- 2192902 TI - Complement-dependent antibody-mediated cytotoxicity in the spontaneously diabetic BB/OK rat: association with beta cell volume density. AB - The present study examined in the spontaneously diabetic BB/OK rat whether a relationship exists between the appearance of complement-dependent antibody mediated cytotoxicity (C'AMC) in serum and the relative beta cell volume density determined in pancreatic biopsies. C'AMC was estimated by 51Cr release from prelabeled major histocompatibility complex-compatible neonatal rat islet cells after exposure to rat serum and rabbit complement. Fifty-one percent (72/141) of sera from BB/OK rats with newly diagnosed diabetes were positive for C'AMC. At onset of hyperglycemia, insulin-immunoreactive beta cells were only detectable in pancreas biopsies of 25% (10/40) of the BB/OK rats who displayed mild hyperglycemia (plasma glucose 8.3-13.0 mmol/l) and low serum C'AMC. A twofold increase (p less than 0.01) of C'AMC and loss of the remaining beta cells was evident in untreated animals upon their reexamination within 1 week after diagnosis of hyperglycemia. Initiation of insulin therapy prevented neither the increase in C'AMC activity nor the decrease in the beta cell volume density. In contrast, three out of four mildly hyperglycemic BB/OK rats treated with cyclosporin A maintained both their initial C'AMC levels and relative beta cell volume density not only throughout the treatment period (4 weeks) but also for at least 4 weeks thereafter. In one additional animal receiving cyclosporin A no protection of the remaining beta cells could be achieved and C'AMC levels were markedly increased. It is concluded that the appearance of increased C'AMC in serum may reflect autoimmune reactions against the islet beta cells of spontaneously diabetic BB/OK rats. The increase of C'AMC seen in untreated as well as insulin-treated BB/OK rats, which were even devoid of beta cells, suggests that C'AMC activity appears secondary to the loss of beta cells. These results do not support the hypothesis of a direct beta cell destruction via intrainsular complement activation. PMID- 2192903 TI - Elevated expression of Pgp-1 (Ly-24) by murine peritoneal B lymphocytes. AB - B cell expression of the surface glycoprotein, Pgp-1 (Ly-24), was evaluated using flow cytometric analysis. Pgp-1 expression on naive, conventional (splenic) B cells was low but could be increased by mitogenic stimulation. Pgp-1 expression on naive peritoneal B cells was higher than expression by unmanipulated conventional B cells, suggesting the possibility that peritoneal B cells have been activated in vivo. However, the elevated expression of Pgp-1 by peritoneal B cells was not accompanied by increased expression of surface Ia but was correlated with Ly-1 status. Further, Pgp-1 expression by B cells from germ-free mice did not differ from that of normal animals. The elevated expression of Pgp-1 by peritoneal B cells is superficially similar to that provoked by mitogenic stimulation of conventional B cells; however, several characteristics suggest that the elevated expression of Pgp-1 by peritoneal B cells does not reflect prior activation of these cells. PMID- 2192904 TI - Eosinophil cytotoxicity enhancing factor: purification, characterization and immunocytochemical localization on the monocyte surface. AB - The monokine eosinophil cytotoxicity enhancing factor (ECEF) increases antibody dependent cytotoxicity of eosinophils towards helminth larvae. A monokine biochemically indistinguishable from ECEF increases the release of leukotriene C4 and other arachidonic acid metabolites by eosinophils. We have developed monoclonal antibodies (mAb) to these monokines by immunizing mice with ECEF made by the U-937 histiocytic lymphoma cell line. mAb 81.10.C9 (IgG2b) and 9A6G (IgG1) inhibit the effect of the monokine on release of AA products. Both mAb bind ECEF, which appears after affinity chromatography purification as a major 13-14-kDa and a minor 62-kDa component (13-14 kDa and 52 kDa after reduction) in silver-stained gels. An additional component of 30 kDa is detectable after radioiodination of the immunopurified material. The specificity of both mAb was studied in several ways. In immunoprecipitation, both recognize the 13-14-kDa and the 30-kDa components, while the 62-(52)-kDa protein is not significantly precipitated. Both mAb react in enzyme-linked immunosorbent assay with products secreted by peripheral blood mononuclear cells and monocytes, as well as with those secreted by phorbol 12-myristate 13-acetate and lipopolysaccharide-stimulated U-937 cells and with the immunopurified proteins. These were separated in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, electroeluted and assayed for ECEF activity. Activity was associated with the 13-14-kDa and the 30-kDa fractions, as seen by increased eosinophil antibody-dependent adherence to schistosomula and cytotoxicity. Granulocyte-monocyte-colony-stimulating factor and interleukin 1, but not tumor necrosis factor, could be detected in crude U-937 supernatants. However, active immunopurified ECEF has no activity in assays for granulocyte monocyte-colony-stimulating factor, interleukin 1 or tumor necrosis factor. Immunocytochemical localization of ECEF employing the mAb shows strong surface staining of viable monocytes and U-937 cells, suggesting that ECEF is associated to the cell surface. These properties distinguish ECEF from other monokines previously reported to activate eosinophils. PMID- 2192906 TI - Glial cells form boundaries for developing insect olfactory glomeruli. AB - Like many other first-order olfactory centers, the olfactory lobe of the moth brain is organized into histologically conspicuous synaptic glomeruli delimited by glial cells. These glomeruli in the moth offer an advantageous system in which to study the parcellation of central neuropils during development. In this article, we review the evidence that glial cells play an essential role in the induction of glomeruli by olfactory sensory axons, and we present new evidence that leads us to propose that a major role for glia in the development of glomeruli is to define for ingrowing dendrites of second-order olfactory neurons edges that lead to the formation of these cells' characteristic morphology. PMID- 2192905 TI - N-methyl D-aspartate (NMDA) evoked changes in blood pressure and heart rate from the rat superior colliculus. AB - Electrical stimulation and microinjections of the GABA antagonist bicuculline methiodide into the superior colliculus (SC) of the anaesthetized rat can evoke changes in blood pressure and heart rate. The long latency of bicuculline evoked responses, however, raises the possibility that they may have been produced by the diffusion of bicuculline to surrounding tissue, in particular, the periaqueductal gray. Thus, the purpose of the present study was to investigate whether such changes could have been produced by the activation of extracollicular neural elements. This was achieved by assessing the relative regional sensitivity of the SC and underlying structures (periaqueductal gray and dorsal tegmentum) with microinjections of the excitatory amino acid N-methyl D aspartate (NMDA) for the production of short latency pressor responses. Dorsal midbrain injections of NMDA (200 nl of 100 mM) in the Saffan anaesthetized rat evoked clear short latency (single or double phase) increases in blood pressure accompanied in most cases by a longer latency increase in heart rate and respiration. Two regions within the dorsal midbrain contained significantly higher proportions of active sites compared with surrounding tissue: i) the superficial and intermediate layers of rostromedial SC, and ii) the caudal periaqueductal gray. The distribution of active sites indicated that pressor responses elicited from the rostromedial SC could not be explained by the diffusion of NMDA to underlying tissue. The question of whether the rostromedial SC might represent an early link in the circuitry responsible for organizing defensive movements and appropriate physiological changes to potentially dangerous overhead stimuli is considered. PMID- 2192907 TI - Myelin-associated inhibitors of neurite growth. AB - CNS myelin and oligondendrocyte membranes contain two minor proteins with strong inhibitory effects on growing neurites (neurite growth inhibitors NI-35 and NI 250). Monoclonal antibodies (IN-1, IN-2) were obtained that neutralize this activity in a variety of culture assays including adult rat optic nerve explants, which are invaded by growing neurites under the influence of these antibodies. In vivo, corticospinal tract lesions in young rats are known to be followed by abortive sprouting, not exceeding 1 mm of elongation. In contrast, the presence of antibody IN-1 led to regrowth of corticospinal axons over more than 5 mm within 2-3 weeks. In development, a negative guidance or channeling function may be associated with these inhibitors for late growing CNS tracts. In fact, application of antibodies or absence of oligodendrocytes during the first postnatal week led to severe anatomical disturbance of the developing rat corticospinal tract. Additional, e.g., stabilizing functions for these inhibitors in the adult CNS remain to be investigated. PMID- 2192908 TI - Axonal outgrowth by identified neurons in the spinal cord of zebrafish embryos. AB - The spinal cord of early zebrafish embryos contains a small number of neurons per hemisegment. The earliest neurons are identifiable as individual neurons or small groups of homogeneous neurons and project growth cones that follow stereotyped, cell-specific pathways to their targets. These growth cones appear to bypass some axons but follow others during pathfinding, suggesting that they can distinguish among the different axons they normally encounter. Furthermore, identified growth cones exhibit cell-specific behaviors in apparent contact with the floor plate cells, which are found at the ventral midline of the early cord. These observations suggest the testable hypothesis that the floor plate may mediate multiple, cell-specific actions on identified growth cones in the zebrafish cord. One hypothesized action is inhibition of specific growth cones to prevent them from crossing the ventral midline. PMID- 2192909 TI - Expression of adhesion molecules and the establishment of boundaries during embryonic and neural development. AB - Evidence is accumulating that molecules involved in cell-cell and cell-substratum interactions are important in the establishment and maintenance of borders between cell groups during development. In this report, we review evidence supporting this conclusion, particularly in regard to the role of adhesion molecules in the formation of cell collectives and in the modulation of cell and neurite movements. PMID- 2192910 TI - Oligodendrocyte-derived J1-160/180 extracellular matrix glycoproteins are adhesive or repulsive depending on the partner cell type and time of interaction. AB - We have studied the functional involvement of J1-160 and J1-180 in the interaction between oligodendrocytes and neurons, astrocytes, or L cells in short and long-term adhesion assays using monoclonal antibodies directed against topographically distinct epitopes on the molecules. Whereas antibodies to mouse liver membranes and monoclonal antibody 597 do not interfere with neuron oligodendrocyte or astrocyte-oligodendrocyte adhesion after 30 min of coculture, antibodies 596, 619, and 620 interfere with astrocyte to oligodendrocyte and neuron to oligodendrocyte adhesion. The adhesion of L cells to oligodendrocytes is not affected by the antibodies. When neurons or astrocytes are cultured on oligodendrocytes for more than 30 min, monoclonal antibody 619 continues to reduce adhesion of astrocytes to oligodendrocytes after 1 and 2 h. However, during this time period the antibody affects neuron to oligodendrocyte adhesion in a different manner. It does not interfere with adhesion of neurons to oligodendrocytes at 1 h and enhances the adhesion of neurons to oligodendrocytes after 2 h of coculture. After 6 and 24 h of coculture, antibody 619 does not affect the adhesion of neurons or astrocytes to oligodendrocytes, suggesting that other adhesive mechanisms are predominant at later times of interaction. At all times studied, neurons and astrocytes adhered well to the oligodendrocytes. To study the influence of the J1 molecules on neuronal interactions in the absence of other oligodendrocyte-derived cell surface components, purified J1-160 was coated as a substrate and neuron attachment was measured as a function of time. Two hours after plating neurons adhered well to J1-160, as they did to laminin, while cell detachment was subsequently observed from J1-160, but not from laminin. These results implicate J1-160 and J1-180 in a recognition process between oligodendrocytes and neurons or astrocytes, but not fibroblasts. This recognition process appears to merge into adhesion or stabilization of cell contacts for astrocytes and destabilization of cell interactions or repulsion for neurons. It is likely that these two opposite effects in cell behavior elicited by the J1 molecules result from differential intracellular responses to a cell surface trigger possibly mediated by different cell surface receptors and/or different consequences in intracellular signaling networks. PMID- 2192912 TI - Morphological, morphometric and stereological study of submandibular glands in rats with lesion of the anteroventral region of the third ventricle (AV3V). AB - Lesions of the antero-ventral region of the third ventricle induce in the rat submandibular gland parenchyma, atrophy through vascular ischemia, and simultaneously increased fibrosis of the connective tissue, probably by alteration of the pituitary gonadotropins (FSH, LH), thyrotrophic hormone (TSH), growth hormone and probably insulin levels. PMID- 2192911 TI - The hepatic glutathione system--influences of xenobiotics. AB - The hepatic glutathione (GSH) system and the influences of xenobiotics have been reviewed. Key steps in the regulation of hepatic GSH are GSH biosynthesis, the GSH-peroxidase/reductase cycle, the cystathionine pathway, and the carrier mediated export processes. Influences of xenobiotics on these different pathways are discussed. Xenobiotics may lead to liver injury after biotransformation to highly reactive electrophilic metabolites (mainly cytochrome P-450 mediated), which easily conjugate with GSH, thus producing GSH depletion. This GSH depletion and probably an additional loss of protein sulfhydryl groups cause a disturbance of the intracellular calcium homeostasis which leads to an irreversible cell injury. The different acinar distribution of cytochromes P-450 and of GSH and GSH related detoxication pathways points to a greater susceptibility of perivenous hepatocytes to xenobiotic-induced damage. Also, the intracellular compartmentation of GSH is important for the understanding of hepatocellular injury induced by several xenobiotics. PMID- 2192913 TI - Inhibition of lung damage caused by paraquat with lymphokines or cytokines. AB - Gramoxone, containing paraquat as an active ingredient can cause severe lung injury in both humans and experimental animals. Biologically active fibroblast stimulating factors produced by lymphocytes and macrophages may be of importance in the development of interstitial fibrosis. In our present study we have attempted to inhibit the process of paraquat induced lung fibrosis by lymphokine enriched supernatants from concanavalin A stimulated spleen cell cultures. It was found that adequate supernatant treatment significantly reduced PQ-induced lung injury and its associated inflammatory response. PMID- 2192914 TI - Expression in Escherichia coli of a sub-gene encoding the lipoyl domain of the pyruvate dehydrogenase complex of Bacillus stearothermophilus. AB - A sub-gene encoding the lipoyl domain (residues 1-85) of the lipoate acetyltransferase chain of the pyruvate dehydrogenase complex of Bacillus stearothermophilus was over-expressed in Escherichia coli. Approx. 80% of the domain was unlipoylated but most of the remainder was correctly lipoylated on Lys 42 and could be reductively acetylated by the B stearothermophilus enzyme complex. A small proportion (approx. 4%) of the domain carried an aberrant substituent, possibly an octanoyl group, on Lys-42. The 400 MHz 1H NMR spectra of the lipoylated and unlipoylated domains were essentially identical and closely resembled that of the native lipoyl domain. PMID- 2192915 TI - Molecular weight analysis of isopenicillin N synthase by electrospray mass spectrometry. AB - The use of electrospray mass spectrometry as a tool in analytical biochemistry was illustrated by determination of the molecular weights of wildtype and recombinant isopenicillin N synthase (IPNS). The molecular weight of recombinant IPNS produced using an expression system which generated soluble protein was found to be between 38,364 and 38,376 Da, ca 60 mass units higher than that of the wildtype material, consistent with the presence of an additional N-terminal glycine in the former. Observed molecular weights were all ca 70 Da higher than that calculated from sequence information, consistent with the complexion of a partially hydrated iron atom to the enzyme during analysis. PMID- 2192916 TI - Amino-terminal sequence of the 21 kDa apoprotein of a minor light-harvesting pigment-protein complex of the Photosystem II antenna (LHC IId/CP24). AB - The 21 kDa apoprotein of LHC IId, a minor light-harvesting antenna component of Photosystem II, has been isolated and subjected to N-terminal protein sequencing. A sequence of 66 residues was obtained which contains regions of considerable homology to both those reported for LHC II and LHC I, but which is obviously distinct from them. The proposed occurrence of an identical 21 kDa LHC subunit in both photosystems I and II is shown to be incorrect. PMID- 2192917 TI - Sexual transmission of human immunodeficiency virus: virus entry into the male and female genital tract. World Health Organization, Global Programme on Acquired Immune Deficiency Syndrome. PMID- 2192919 TI - Dr. Georgeanna Seegar Jones: a pioneer in reproductive endocrinology. PMID- 2192918 TI - On the maintenance of male fertility in the absence of native testosterone secretion: site-directed hormonal therapy in the rat. AB - A method of direct percutaneous injection of testosterone (T)-laden microspheres directly into the testis was used in an attempt to achieve the maintenance of normal intratesticular T concentrations, spermatogenesis, and fertility. Rats were divided into three groups: (1) sham operated/injection controls; (2) animals receiving 250 micrograms/d gonadotropin-releasing hormone (GnRH)-antagonist; and (3) animals receiving GnRH-antagonist as in group 1 plus 20 mg T-laden microspheres/testis. Treatment periods were 45 and 90 days. Serum T, testicular interstitial fluid T, testis weights, epididymal weights, daily sperm production (sperm x 10(6)/g/d), cauda sperm motility, and fertility were assessed in all animals. Gonadotropin-releasing hormone antagonist treatment reduced serum and testicular interstitial fluid to below detectable levels at day 45 and to similar levels at day 90. Supplementation with T-laden microspheres maintained testicular interstitial fluid T at concentrations not different from controls without elevation of serum T concentrations. All other values, including fertility were suppressed by GnRH-antagonist treatment and maintained by supplementation with T laden microspheres. PMID- 2192920 TI - Corpus luteum: composition and function. PMID- 2192921 TI - Time trends in risk factors and clinical outcome of ectopic pregnancy. AB - Ectopic pregnancy (EP) admissions at The Johns Hopkins Hospital were reviewed for 160 patients admitted from 1970 to 1974 and 253 patients from 1980 to 1984. Over the decade, average annual admissions for EP increased by 64%, and a higher proportion of cases in 1980 to 1984 were unmarried women with no insurance coverage. There were significant increases in cases with a history of sexually transmitted diseases (from 19.1% to 31.6%) and in recurrent EPs (7.6% to 19.0%) but declines in EP associated with contraceptive failures. Newer diagnostic techniques such as quantitative serum human chorionic gonadotropin assays, pelvic ultrasound, and laparoscopy were more frequently used in the 1980 to 1984 period, resulting in less severe morbidity on admission, more conservative surgical management, and reduced length of hospitalization. Thus, although admissions for EP have increased, the severity of illness has been reduced by earlier diagnosis and more conservative management. PMID- 2192922 TI - [Glass ionomer cement as dental filling material]. PMID- 2192923 TI - Production and application of monoclonal antibody specific for human chorionic gonadotropin. AB - Spleen cells from mice immunized with human chorionic gonadotropin (hCG) were fused with mouse myeloma cells and four hybridomas, secreting monoclonal antibodies, were selected for further studies. In cross-check tests against tissue extracts and peptide hormones it was established that mAb IB10 (IgG1) reacted positively against hCG only but not with other hormones. Ascites from this hybridoma was fractionated by ammonium sulphate precipitation and by FPLC to isolate the IgG fraction. Subsequently, the purified mAb was conjugated with horseradish peroxidase and used for development of a simple test for pregnancy diagnosis. Some preliminary experiments have shown that the test is very specific and reproducible. PMID- 2192924 TI - Cornified cell envelope. AB - The cornified cell envelope (CE) is a highly insoluble structure on the inside of the plasma membrane of terminally differentiated keratinocytes. The cellular and molecular biology of the CE is outlined and new areas of research involving the CE are reviewed focussing on morphological and biochemical connections, the sequential gene expression during terminal differentiation, the interaction of lipids and proteins forming the epidermal barrier, the cysteine-rich pool of proteins in the epidermis as well as the molecular cloning and/or characterization of major components of the CE. PMID- 2192925 TI - Dermatomyositis and malignancy. A multicenter cooperative study. AB - A retrospective analysis of 118 cases of dermatomyositis (DM) collected in 22 departments of dermatology over a 5-year period is presented. 34 cases (28%) were associated with a cancer that was diagnosed more than 1 year prior to (7 cases), concomitantly (22 cases) or more than 1 year after (5 cases) the occurrence of DM. There was a clear correlation between the evolution of DM and a cancer paraneoplastic evolution in 8 cases only (22%). In most of the cases, no extensive diagnostic procedures were necessary for identifying the tumors. 58% of the patients with cancer-associated DM died 20 (8-29) months after the diagnosis of DM. This multicenter study based on a short period of time confirms and extends previous observations based on retrospective single-center analyses. PMID- 2192926 TI - Papular and nodular mucinosis as a sign of lupus erythematosus. AB - We describe 3 cases of papular and nodular mucinosis (PNM), a clinically distinctive cutaneous mucinosis associated with lupus erythematosus (LE), which has received little attention in the dermatologic literature. Histopathology shows deposits of mucin in the dermis without microscopic features of LE, while immunofluorescent studies disclose linear or granular deposits of IgG, IgM and C3 at the dermoepidermal junction. In about 80% of the 14 cases described in the literature, PMN has been associated with systemic LE with prevalent joint and kidney involvement. The possible prognostic significance of this singular dermatosis is discussed. PMID- 2192927 TI - A case of linear IgA bullous dermatosis of childhood: immunoelectron microscopic and IgA subclass studies. AB - A 2-year-old girl developed small tense bullae on the diaper area, face and extremities. Immunofluorescent studies revealed linear deposits of IgA, IgM and C3 at the basement membrane zone (BMZ). In addition, IgA2 deposits, as well as IgA1, were clearly demonstrated in the lesional skin. However, in circulation, only IgA1 anti-BMZ antibodies were found. Immunoelectron microscopic study showed IgA deposits just underneath the basilar surface of the basal cells, which seemed to be associated with hemidesmosomes. The survey of the literature suggests that the involvement of IgA2 is extremely rare in this disease. PMID- 2192928 TI - Distribution of retinoids in the chick limb bud: analysis with monoclonal antibody. AB - Retinoic acid induces anteroposterior duplicate formation in developing chick limb bud, and it may be a natural morphogen involved in limb pattern formation. Retinoic acid is produced from retinol locally in the limb bud via retinal, and thus, to elucidate the distribution of these retinoids in the limb bud seems to be important for the understanding of the morphogen formation. We produced a monoclonal antibody against the retinoids with BSA-RA (bovine serum albumin retinoic acid) conjugate for antigen, and investigated the distribution of retinoids in the chick limb bud. The antibody predominantly bound to retinoic acid, but weakly to retinol and retinal. Retinoids appeared in the limb bud at stage 18 and were distributed through stages 20-24, when the pattern formation in distal mesoderm was in progress. Initially they were found evenly in the whole mesoderm, but disappeared gradually from core mesoderm and remained only in the region of peripheral mesoderm at stage 24. At stage 26, retinoids were detected only in ectoderm. These results support the idea that the retinoids actually play roles in limb pattern formation and suggest that the retinoids in the peripheral mesoderm are important for pattern formation. Further, the role of retinoids in epidermis development at later limb bud stages is also suggested. PMID- 2192929 TI - A hyaline layer protein that becomes localized to the oral ectoderm and foregut of sea urchin embryos. AB - An antigen is described which is a marker for the oral ectoderm and foregut of the sea urchin embryo. In Lytechinus variegatus, the antigen is first detectable by immunofluorescence on the surface of fertilized eggs, and remains globally distributed through the early stages of gastrulation. Thereafter the antigen is localized to the oral ectoderm and foregut, coincident with the morphogenesis of these regions. The antigen is a large, detergent-insoluble, filamentous glycoprotein associated with the tips of the microvilli in the hyaline layer. This glycoprotein is present in two forms, a approximately 350-kDa form that is maternally synthesized and a much larger form which is synthesized at late gastrula stage as a 350-kDa precursor before becoming modified and assembled into the hyaline layer. The timing of synthesis of the zygotic form of the molecule correlates precisely with the localized expression of the antigen. The antigen copurifies with intact hyaline layers and cosediments with hyalin in the presence of calcium, suggesting that it is a structural component of the hyaline layer. PMID- 2192930 TI - Discriminating and responsiveness abilities of two hearing handicap scales. AB - Several scales exist for screening handicap and assessing rehabilitation in elderly individuals with hearing loss. There are few comparative studies, however, to suggest which scales perform best. Using receiver-operating curves and responsiveness indices, we examined the relative discriminating ability and sensitivity to detect change of four scales: a long and short version of the Hearing Handicap Inventory in the Elderly (HHIE-L, HHIE-S), and a long and short version of the Revised Quantified Denver Scale of Communication Function (RQDS-L, RQDS-S). All scales were administered to 137 elderly veterans with hearing loss and 101 elderly veterans without hearing loss. Follow-up testing to determine relative ability to detect change was assessed in hearing impaired individuals only after they had used a hearing aid for 4 months. Discriminative accuracy for correctly identifying individuals with hearing loss were: HHIE-L 78%, HHIE-S 79%, RQDS-L 73%, and RQDS-S 74%. Overall differences between the HHIE-S and the RQDS-S were not statistically significant (p = 0.06). True positive results were greater with the HHIE-S compared to the RQDS-S (p = 0.03). Responsiveness indices were: HHIE-L 1.78, HHIE-S 1.86, RQDS-L 1.04, and RQDS-S 1.07. Differences between the HHIE-S and the RQDS-S were statistically significant (p less than 0.05). We conclude short versions of the HHIE and RQDS are as accurate and sensitive for detecting change as long versions, and the HHIE-S is a superior versatile instrument for screening and assessing rehabilitation in elderly individuals with hearing impairment. PMID- 2192931 TI - Monoclonal antibody against human enterokinase and immunohistochemical localization of the enzyme. AB - A monoclonal antibody, hek-1, was raised against enterokinase or enteropeptidase that had previously been partially purified from human duodenal fluid. Hek-1 showed staining of two glycoprotein bands of relative molecular weights of 260,000 and 240,000 on immunoblot analysis of partially purified enterokinase and of ammonium sulfate fraction of duodenal fluid. An enzyme immunoassay for human enterokinase was developed, making use of hek-1. Sensitivity to enterokinase was 20 times higher than that of the conventional assay where BAPA was used as a substrate. The immunohistochemical study with hek-1 showed staining of the brush border membrane and some goblet cells of the duodenum and upper jejunum but no staining of the colon epithelium. PMID- 2192932 TI - Immunohistochemical study of pre-S(2) antigen in liver and serum of patients with chronic hepatitis B. AB - To evaluate the significance of pre-S(2) in the liver, the authors studied the relationship between serum and intrahepatic pre-S(2) in 27 patients with chronic hepatitis B. Intrahepatic expression of pre-S(2) was observed under light and electron microscopy and compared with that of HBsAg and HBcAg. All patients were positive for hepatic pre-S(2), and 25 for serum pre-S(2). Intrahepatic pre-S(2) expression was membranous or both membranous and cytoplasmic in 18 cases and was cytoplasmic in 9. The serum levels of pre-S(2) were significantly higher in cases whose intrahepatic pre-S(2) was membranous than in the cytoplasmic cases. These findings indicate that membranous expression of pre-S(2) reflects its secretion into the circulation. Intrahepatic pre-S(2) expression was found almost completely to resemble that of HBsAg on both light and electron microscopy. Membranous pre-S(2) was seen in the liver of 16 of 25 cases who were positive for intrahepatic HBcAg. In detailed studies of membranous pre-S(2) and HBcAg, both membranous pre-S(2) and HBcAg appeared in the liver of all 7 cases before or at the peak of acute exacerbation, but after it, membranous pre-S(2) was not found in 4 of 8 cases. These results suggest that disappearance of membranous pre-S(2) and HBsAg may be related to hepatic cell necrosis in some cases with acute exacerbation. PMID- 2192934 TI - [Vascular endothelium (review). I. General morphology. 2A: histogenesis of the vascular endothelium]. AB - Determination, differentiation, and specialization of vascular endothelium are the main steps of its histogenesis. The source of the first determined endothelioblasts are condensed mesenchymal cells (blood islands) at the yolk sac (extraembryonal) and also in the intraembryonal mesenchyme. The term of determination is not yet known. The marginal cells of the blood islands differentiate into primordial endothelial cells forming primitive vessels by migration, proliferation, fusion, and selection. This "vasculogenesis" is induced by specific matrix components produced by the endothelioblasts themselves and other not known factors. Formation of secondary capillary plexuses is related to organogenesis and takes place by sprouting from preexisting endothelium ("angiogenesis"). Factors which induce and promote angiogenesis were isolated from different embryonic organs. Migration, proliferation, and tube formation are regulated by extracellular matrix components (fibronectin, laminin). Main features of primordial endothelium of protocapillaries are: irregular profile, abundance of synthetic organelles, lack of plasmalemmal vesicles and basement membrane, production of specific matrix components. Specialized endothelium (continuous, fenestrated, discontinuous a.s.o.) develops from secondary plexuses influenced by factors of the specific organ tissue. The probably mechanism by which the endotheliocytes reach their final shape and behavior is discussed; some morphological and functional properties during maturation are documented. The maturation of endothelium is related to establishing of the specific blood-tissue barrier. PMID- 2192933 TI - Analysis of interaction between insulin binding and insulin effect on primary culture of normal and db/db mouse hepatocytes. AB - Insulin binding and the characteristics of insulin receptors were studied in primary cultures of hepatocytes isolated from genetically diabetic mice (db/db mice). In addition glycogen synthesis in these hepatocytes was studied as one of the indicators of insulin action after binding to the receptors. The maximum insulin binding of db/db mice hepatocytes was 46% of control. There was no significant difference in insulin binding affinity between db/db and normal mice hepatocytes. In db/db mice, no insulin effect on glycogen synthesis was recognized. On the contrary, in the experiment on hepatocytes from normal mice exposed to insulin to induce down-regulation of insulin receptors (insulin pretreated), the effect of insulin on glycogen synthesis was less but maintained. After re-culture of the insulin-pretreated hepatocytes with insulin-free medium, insulin binding and the insulin effect were restored. However, no apparent changes of insulin binding or the insulin effect on glycogen synthesis were recognized in hepatocytes from db/db mice under the same condition. These results suggested that the impaired process after insulin binding might play an important role, in addition to the decreased capacity of insulin binding, in the pathogenesis of DM in db/db mice. PMID- 2192935 TI - [Vascular endothelium (review). I. General morphology. 2B: phylogenesis of the vascular endothelium]. AB - The phylogenetic descent of vascular endothelium from mesenchyme--derived precursors is described related to the development of a vessel--bound microcirculation. Endothelial precursors in primitive animals may have migrated into tissue clefts gradually forming vascular tubes. True microcirculatory vessels at first appear in the nemertines, a closed vascular system is present in some annelids whereas in arthropods an open lacunar system predominates. The first appearance of true endotheliocytes is under discussion; the author gives some evidence that it is present already in some annelids. Precursor of the endothelial wall of vessels may be the so called "Leydig's membrane", covered with amoebocytes and other mesenchymal cells. The molluscs exhibit many variants of endothelium. In the fishes, the vascular system begins to split into a blood and a lymphatic system. Obviously the specialization of endothelium correlates with the level of evolution. Despite the complicated course, the evolution of endothelium may be regarded as monophyletic. PMID- 2192936 TI - [Maternal cardiovascular adaptation in pregnancy]. AB - Maternal cardiovascular adaptations during pregnancy, such as cardiac output, blood volume, hormones, water and electrolyte balance, arterial blood pressure, vascular resistance, uterine blood flow amongst others ensure the well-being of the mother and of the fetus. Several of these changes are not yet well understood. This report reviews the factual changes in cardiovascular physiology during pregnancy. Methodological experimental problems are identified and their relationship to the interpretation of the data discussed. Open scientific questions are identified and the experimental designs necessary to answer them are discussed. The possible mechanisms which are responsible for these changes are addressed. Special attention is given to arterial blood pressure during pregnancy as the regulated variable. It is shown how cardiovascular parameters are involved in the regulation of blood pressure and the signals, which trigger these changes. The effects of the vasoactive agents, angiotensin II and catecholamines, on the circulation during pregnancy are reviewed. Alterations of baroreceptor function are discussed for this time period. Further investigations should assess venous function during pregnancy to elucidate mechanisms by which such maternal adaptations occur. PMID- 2192937 TI - [Pregnancy outcome with intensified insulin therapy in manifest diabetes]. AB - In 1981, the intensified insulin therapy for achievement of euglycaemia in pregnant diabetics was introduced at the University Department of Obstetrics and Gynaecology in Cologne. This study compares the results of 112 pregnancies in women with overt diabetes monitored before (1971-1980) or after (1981-1988) changing the therapeutic regimen. In the period from 1981 to 1988, the proportion of euglycaemic patients (preconceptionally 19%, before delivery 79%) was clearly higher than from 1971 to 1980 (n = 42; 7% and 9%, respectively). The tight blood glucose control resulted in a doubling of hypoglycaemic episodes during pregnancy. The proportion of preterm deliveries was reduced from 47% to 24%. The rate of caesarean sections was nearly constant (1971-1980: 38%, 1981-1988: 34%). The marked success of therapy was the decrease of perinatal mortality from 20.9% to 2.9%. The perinatal morbidity also diminished, as shown by the decreasing rates (30-90%) of foetopathy, macrosomy, respiratory distress syndrome, birth trauma, hypoglycaemia, hypocalcaemia and polycythaemia. The malformation rate, however, remained high (1971-1980 = 7%, 1981-1988 = 11%). The results demonstrate the necessity of a strict blood glucose control during pregnancy, beginning before the time of conception. PMID- 2192938 TI - [Introital sonography--a new method in the diagnosis of bladder function]. AB - In this study we introduce a non-invasive sonographic method called "introital sonography" which enables concomitant urodynamic measurements for evaluating the bladder function. During cystometry, urethral pressure profilometry and uroflowmetry, 20 patients with the symptom "loss of urine" and 10 healthy volunteers showed typical sonographic and urodynamic patterns, especially with regard to stress incontinence and urge incontinence. In contrast to video urethrocystography, the lack of radiation exposure is advantageous. In contrast to perineal sonography, introital sonography allows simultaneous urodynamic measurements with applied catheters avoiding topographic and tonometric artifacts. PMID- 2192939 TI - [Inca and paternal anxiety or ultrasound hair tangle]. AB - A villous tumour on the occiput of his own unborn daughter is followed up by the author, using serial ultrasound examinations. On closer investigation, the tumour is identified as a very prominent mop of hair on the occiput of the foetus. Differential diagnosis (which also reflects paternal anxiety) includes hygroma colli, which may present a similar ultrasonographical appearance. PMID- 2192940 TI - [Hermann Johannes Pfannenstiel (1862-1090). On the 80th anniversary of his death. A biography of a famous German gynecologist]. AB - The gynaecologist Hermann Johannes Pfannenstiel died 80 years ago, on July 3, 1909, from the sequelae of an occupational accident. His death marked the unexpected end of a splendid career as a physician, whose heritage in terms of humanity and scientific achievements is most impressive, even today. Pfannenstiel was born in Berlin on June 28, 1862. He studied medicine in Berlin (1880-1885) against his father's wishes and was therefore deprived of any financial support. Nevertheless, he completed his studies and his doctorate thesis ("summa cum laude") in 1885. Pfannenstiel was trained by v. Rabenau (Berlin; gynaecology), Pauly (Posen; surgery, internal medicine) and Fritsch (Breslau; gynaecology), and became a lecturer at the University of Breslau in 1890 ("Habilitation"). In 1889 he married Elisabeth Behlendorff, and in 1890 his only son Wilhelm was born. In January 1894 he established a private practice in Breslau until he was awarded a professorship in 1896. In the same year he became director of the Department of Gynaecology at a hospital in Breslau (Krankenhaus der Elisabethinerinnen), where he developed in 1900 his world-famous transverse laparotomy technique (suprasymphysarer Faszienquerschnitt) named after him ("Pfannenstiel Querschnitt"). From 1891 he was secretary of the German Society for Gynaecology (Deutsche Gesellschaft fur Gynakologie) and since 1896 he was co-editor of the Archives of Gynaecology (Archiv fur Gynakologie). In 1902 Pfannenstiel was offered the chair of Obstetrics and Gynaecology at the University of Giessen to succeed Chr. A. H. Lohlein, who had died in 1901. He rejected three other chairs at Leyden (Holland), Erlangen and Freiburg which were offered to him in 1904.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2192941 TI - Transvaginal ultrasound evaluation of myometrial invasion in endometrial carcinoma. AB - In 20 cases of histologically proved endometrial cancer the depth of myometrial invasion was ascertained by means of transvaginal ultrasound, using a high frequency endocavitary probe. The sonographic findings were confirmed by histologic examination in 18 of the 20 patients evaluated (90.0%). Transvaginal ultrasound provides a fuller preoperative clinical picture and supplies additional diagnostic information which is invaluable in the choice of therapeutic approach. PMID- 2192942 TI - Leukaemia is a genetic disorder of somatic cells. PMID- 2192943 TI - Idarubicin in the treatment of acute leukemias. An overview of preclinical and clinical studies. AB - Idarubicin is a new derivative of Daunorubicin which was found to be more potent and more active than Daunorubicin and Doxorubicin in several experimental leukemias. Its antileukemic activity in preclinical models prompted the introduction of Idarubicin into clinical studies. As a single agent, Idarubicin produced complete remission in 20% and 30% of patients with heavily pretreated pediatric and adult acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) respectively. Idarubicin combined with Cytarabine and/or other antileukemic agents produced complete remissions in 46% of patients with refractory or relapsed AML and in 58% of patients with refractory or relapsed ALL (adult and pediatric). Subsequently, Idarubicin has been employed in untreated AML patients in combination with Cytarabine and/or Etoposide, producing complete remissions in more than 80% of patients. In ALL patients the drug has been used in combination with Vincristine, Cytarabine and Prednisone, producing complete remissions in 82% of patients. Recently, Idarubicin has been utilized in combination with intermediate doses of Cytarabine in refractory or relapsed ALL and AML, and 70% of patients achieved complete remission. Preliminary results of ongoing prospective randomized studies in untreated adult AML seem indicate that Idarubicin is at least equivalent, if not superior to Daunorubicin. The antileukemic activity of Idarubicin given orally as single agent, or in combination with other drugs, has been shown in AML and myelodysplastic syndromes. The toxicity of Idarubicin includes mild nausea and vomiting, alopecia and liver dysfunction. Ongoing randomized trials comparing Idarubicin to Daunorubicin should provide more information about the potential cardiotoxicity of this drug. PMID- 2192944 TI - The significance of paraproteinemia in hairy cell leukemia: case report and review of the literature. AB - A case of hairy cell leukemia and IgG paraproteinemia is described. Peripheral blood surface marker analysis, serum paraprotein levels and immunoperoxidase stains of bone marrow sections at diagnosis and after 7 months of interferon treatment suggested the existence of two unrelated pathological B cell clones: one composed of malignant hairy cells and the other secreting the paraprotein. Previously reported cases of hairy cell leukemia with paraproteins are reviewed and our patient's contribution to the understanding of this association is stressed. PMID- 2192945 TI - [Fetal ovarian cysts]. AB - Neonatal ovarian cysts are not rare. Most are small follicular cysts less than 2 cm in diameter; larger cysts are less common. Such cysts are usually discovered when complications occur or when they are occasionally detected on systematic clinical examination. 2 cases are presented in infants in whom the diagnosis was made antenatally by ultrasonic scan. In both the cysts regressed spontaneously during the neonatal period. The perinatal management of ovarian cysts should be conservative as complications are very rare and hasty surgery is unwarranted. PMID- 2192946 TI - [Gene amplification in tumors]. PMID- 2192947 TI - [Mitochondrial myopathy]. PMID- 2192948 TI - [Dysplastic nevus--relation to malignant melanoma]. PMID- 2192949 TI - [Cardiac lesions in systemic lupus erythematosus]. PMID- 2192950 TI - [Combined spina-bifida clinic]. PMID- 2192951 TI - [Influence of folate deficiency on neurologic and mental disorders]. PMID- 2192952 TI - [Predisposition of the elderly to heat stroke; etiology, diagnosis and prevention]. PMID- 2192953 TI - [Isolated organ perfusion in cancer chemotherapy]. PMID- 2192954 TI - [Mechanism, measurement and treatment of insulin resistance]. PMID- 2192955 TI - [Chronic lung disease of infancy]. PMID- 2192957 TI - [Melanocytic tumors of the conjunctiva--a diagnostic and therapeutic problem]. PMID- 2192956 TI - [Immunization for invasive Haemophilus influenzae type b infections: present and future]. PMID- 2192958 TI - [Management of pregnancy and birth during genital herpes simplex infection: update]. PMID- 2192959 TI - [Luteinizing hormone-releasing hormone agonists for treatment of prostatic cancer]. PMID- 2192961 TI - [Role of ultrasound in the diagnosis of appendicitis]. PMID- 2192960 TI - [Dr. Simon Frankel, the first Jewish physician in Eretz Israel]. PMID- 2192963 TI - [Programs for the prevention of anemias of pregnancy]. PMID- 2192962 TI - [The "Ashkelon" hypertension detection and follow-up program]. AB - The program described aims at enhancing awareness of high blood pressure and other risk factors for cardiovascular disease (CVD) and promoting a healthy lifestyle. The study population consisted of 11,000 workers at worksites and visitors to community centers, aged 25-65 years. The program was carried out in cooperation with primary care clinics and non-pharmacological control of high blood pressure was by a community center for prevention of CVD. In 1980, 56.0% of hypertensives were unaware of their condition, while by 1988 this was reduced to 6.1%. Body weight reduction resulted in lowering of blood pressure which enabled cessation of all antihypertensive treatment in 25%. Deep muscle relaxation enabled cessation in 47%. The savings effected in terms of antihypertensive treatment outweight the total cost of the program 3-fold. PMID- 2192964 TI - [Education is no cure-all. Discussing a comprehensive approach to reducing the risk of AIDS]. PMID- 2192965 TI - [Worker's health promotion]. PMID- 2192966 TI - [Dental primary prevention in Israel and its effect on oral health]. PMID- 2192967 TI - [Price of tobacco products and the smoking epidemic]. PMID- 2192968 TI - Bioactivation of hexachlorobutadiene by glutathione conjugation. AB - Glutathione (GSH) conjugation reactions in the metabolism of hexachlorobutadiene (HCBD), in rats and mice, initiate a series of metabolic events resulting in the formation of reactive intermediates in the proximal tubular cells of the kidney. The GSH S-conjugate 1-(glutathion-S-yl)-1,2,3,4,4-pentachlorobutadiene (GPCB), which is formed by conjugation of HCBD with GSH in the liver, is not reactive and is eliminated from the liver in the bile or plasma, or both. GPCB may be translocated intact to the kidney and processed there by gamma-glutamyl transpeptidase and dipeptidases to the corresponding cysteine S-conjugate. Alternatively, gamma-glutamyl transpeptidase and dipeptidases present in epithelial cells of the bile duct and small intestine may catalyse the conversion of GPCB to cysteine S-conjugates. The kidney concentrates both GSH and cysteine S conjugates and processes GSH conjugates to cysteine S-conjugates. A substantial fraction of HCBD cysteine S-conjugate thus concentrated in the kidney is metabolized by renal cysteine conjugate beta-lyase to reactive intermediates. The selective formation of reactive intermediates in the kidney most likely accounts for the organ-specific effects of HCBD. Alternatively, cysteine S-conjugates may be acetylated to yield excretable mercapturic acids. PMID- 2192969 TI - Compartment syndromes of the foot: current concepts. AB - The foot has been mentioned as a site for the development of a compartment syndrome for approximately 9 years. Despite this, very little information exists in the literature containing specifics on the nature of the disorder. Very recent work has shown that crush injuries, forefoot and midfoot fractures and dislocations, and calcaneal fractures are prone to the development of foot compartment syndromes (FCS). The classical clinical signs of pain with passive stretch of the involved muscles, and dysfunction of the nerves that pass through the involved compartments are less helpful in the diagnosis of the syndrome in the foot than elsewhere. Tense swelling of the foot may be of some help in arousing suspicion that a FCS has developed, but the diagnosis is best made by invasive catheterization of the foot compartments. Since recent work has discovered that at least nine foot compartments exist, multi-stick catheterization is recommended. Fasciotomy should be performed when the pressures are significantly elevated, to prevent the development of late contractures. A communication exists between a newly-found compartment of the foot, the calcaneal compartment, and the deep posterior compartment of the leg. A combined pattern of FCS and deep posterior compartment syndromes of the leg exists, and should be remembered by the clinician treating injuries of the foot or leg. Also, a foot injury alone may cause a deep posterior compartment syndrome in the leg. Claw-toe deformity seems to be the primary late sequela of FCS. Local procedures may be of only temporary benefit. PMID- 2192970 TI - [Laser surgery of the cornea]. AB - Photoablation is a new type of laser-tissue interaction that allows the removal of corneal tissue with submicron precision. To date, three potential applications have been developed: (1) peripheral keratectomies; (2) reprofiling of the central cornea; (3) corneal smoothing. Mimicking conventional incision techniques, excimer laser keratectomies indirectly influence the central cornea by mechanically relaxing the peripheral part. The most important clinical application is the correction of astigmatism. By irradiating the central cornea directly, small lenticules of tissue can be removed by making the curvature of the cornea flatter. Complications can arise from repair mechanisms leading to glare or reduction in the initial amount of optical correction. Corneal smoothing using an immersion fluid can be used after lamellar keratoplasty or to remove superficial pathological structures such as band keratopathy and superficial scars. PMID- 2192971 TI - [Incidence and function of Langerhans cells in various corneal diseases]. AB - Using immunohistochemical techniques, we investigated the distribution and frequency of Langerhans cells in corneal buttons obtained from patients who underwent corneal transplantation because of various corneal diseases. The frequency of these dendritic cells was similar to that in the normal epidermis in corneas with epidermalization after severe alkali burns. Numerous Langerhans cells, albeit in smaller numbers, were also present in the central corneal epithelium of patients with keratitis due to infection with herpes simplex virus, keratitis due to herpes zoster virus, bacterial corneal ulcers, corneal scars, corneal ulcers associated with rheumatoid arthritis, and patients with chronic corneal allograft reactions. The presence and persistence of Langerhans cells in diseased corneas may account for, at least in part, a breakdown of corneal immune privilege with a higher rate of rejection episodes after corneal transplantation. Furthermore, it is probable that Langerhans cells as potent antigen-presenting cells may also play an important role in the initiation and the progression of immune responses in various inflammatory corneal diseases. PMID- 2192972 TI - [Decrease in intraocular pressure following administration of the local carbonic anhydrase inhibitor (MK-927)--comparison of the effect with pilocarpine]. AB - We studied the effect of a single dose of the local carbonic anhydrase inhibitor, MK-927, on lowering IOP in 24 patients with bilateral primary open-angle glaucoma or ocular hypertension and compared it with the effect of pilocarpin in 9 patients. Following a washout of any glaucoma medication of 3 to 14 days, a diurnal IOP curve was performed. Two to seven days later one eye received a single drop of 2% MK-927 while the other eye received placebo and the diurnal IOP curve was repeated. MK-927 treated eyes showed a peak mean IOP change of 10.5 mmHg (33.1%) occurring at 4.5 h postmedication. In nine eyes treated with pilocarpin 1% q.d., the mean reduction of the mean IOP was 7.0 mmHg (22.1%) compared to no treatment. The same eyes showed a mean reduction of mean IOP of 6.1 mmHg (18.9%) following a single dose of MK-927. In contrast, the mean reduction of the maximal IOP treated with pilocarpin was 7.3 mmHg (25.8%) and 10.2 mmHg (34.2%) following MK-927. Considering the IOP lowering of MK-927 shown here, the possibility of a topically effective glaucoma therapy by local carbonic anhydrase inhibitor seems to be established. The IOP lowering effect of MK-927 appears to be similar to that of pilocarpin 1%. PMID- 2192973 TI - [Immunohistochemical studies of the human lens capsule]. AB - In this study we made an attempt to localize components of the human lens capsule using immunohistochemical methods. Type IV collagen could be shown in all parts of the capsule in equal distribution. It could be found over the whole thickness of the lens capsule. By comparison, laminin could be detected only at the inner layer of the capsule. There was no difference concerning the contribution of these components between the anterior and the posterior capsule. No specific staining of collagen types I and III or of fibronectin could be found. PMID- 2192974 TI - [Laser scanning in ophthalmology]. AB - The current state of the art for the major laser scanning methods, laser scanning ophthalmoscopy (LSO) and laser tomographic scanning (LTS) is discussed and the function principles are described. Experience with a prototype of each instrument from Rodenstock (LSO) and Heidelberg Instruments (LTS) is reported. LSO imaging of the cornea, vitreous, retina, and optic disc, as well as on-line processing is demonstrated with examples (nerve fibre colour coding and histograms). Measurement of the cornea, optic disc and retinal topography with LTS is also demonstrated with examples. An example of polarization optical imaging of the cornea's assumed interferometric "tension patterns" is shown. The current status and future possibilities of laser scanning, its expanded diagnostic potential with microperimetry, IR scanning angiography and polarization optic imaging and measurement (eg. nerve fibre thickness) is discussed extensively. The safety aspects of laser light exposure of the macula are also mentioned. Laser scanners as imaging and measuring sensors of unknown accuracy open a new area of possibly revolutionary diagnostic possibilities. PMID- 2192975 TI - [The so-called bridle operation]. AB - In two cases of palsy of the third nerve we found a paresis of two neighboring rectus muscles without cyclotropia (i.e., palsy of the medial rectus muscle an the superior rectus muscle). In these cases, we performed a new procedure, which consists in transpositing the two functioning rectus muscles at the insertion of the two paretic muscles. The effect is greater if the transposed muscles are linked with fascia lata behind the globe, as performed in the second case. PMID- 2192976 TI - Lectin-binding sites in the retina of the pig, baboon and cat. AB - There are notable interspecific differences in the lectin binding sites in the retina of mammals. In the porcine retina a distinct labeling of all the neurons of the stratum ganglionare is obtained by use of succinylated wheat-germ agglutinin (WGA-S). In the baboon the stratum ganglionare does not label, though the entire inner plexiform layer can be demonstrated with WGA-S. In the cat WGA-S binds exclusively to the outer segments of the rods and cones. These specific differences will be compared with findings in the human retina [10] and discussed in connection with biochemical results obtained during our studies of the porcine retina. PMID- 2192977 TI - [Deep venous thrombosis. Clinical aspects, diagnosis and therapy]. PMID- 2192978 TI - Long-term treatment of acromegaly with octreotide (Sandostatin). AB - Sixteen patients with acromegaly have been treated with octreotide [100 micrograms twice daily to 200 micrograms 3 times daily according to growth hormone (GH) response] for between 3 and 44 months. The mean serum GH concentrations fell from 39.3 mU/l before treatment to 10.5 mU/l on day 1 of treatment and, with continued treatment (and higher doses in 8 of 16 patients), to 7.9 mU/l. In 2 patients there was no GH suppression. GH suppression after the first administration of octreotide appeared to predict long-term response. Pre treatment serum insulin-like growth factor 1 levels were elevated in 11 of 12 patients investigated, but were normalized on continued octreotide therapy in 10 of 12. Octreotide suppressed prolactin secretion in all 6 hyperprolactinaemic patients. Steatorrhoea occurred in 15 of 16 patients at initiation of treatment, but resolved in all within 7 days. Two patients developed gallstones. In summary, octreotide is a safe and effective treatment for acromegaly, producing clinical and biochemical improvement in up to 90% of patients. Octreotide is a valuable adjunctive treatment where surgery has failed and also in those with contra indications to surgery. PMID- 2192980 TI - Direct estimation of serological H-Y antigen by flow cytometry. AB - This study was undertaken to evaluate the efficiency of flow cytometry in the detection of the serological H-Y antigen, and to survey expression of H-Y in the normal human population. Peripheral blood leukocytes (granulocytes) were reacted with monoclonal H-Y antibody, gw-16, and with FITC-conjugated goat anti-mouse IgG, and then were scored for fluorescence in the flow cytometer. Assigned H-Y phenotype was correlated accurately with sex phenotype in 33 out of 38 women and 62 out of 65 men. Data were evaluated by exploratory data analysis (EDA). PMID- 2192979 TI - Application of the polymerase chain reaction to the diagnosis of human genetic disease. AB - In vitro DNA amplification by means of the polymerase chain reaction is currently revolutionizing human molecular genetics. Since its inception in 1985, a wide variety of different methods and their applications in the diagnosis of disease have been described. This review is intended to serve as a brief guide to current and emerging possibilities in this rapidly expanding field. PMID- 2192982 TI - The analysis of hypervariable DNA profiles: problems associated with the objective determination of the probability of a match. AB - A computerised system has been used to store DNA profiles from 3 hypervariable loci. This initial survey illustrates that band matching is only possible after analysis of the errors associated with electrophoretic systems. A number of databases have been constructed with the three probes investigated and two methods of frequency determination, 'binning' and 'sliding window' fitting, have been compared. PMID- 2192981 TI - The mutational spectrum of single base-pair substitutions causing human genetic disease: patterns and predictions. AB - Reports of single base-pair substitutions that cause human genetic disease and that have been located and characterized in an unbiased fashion were collated; 32% of point mutations were CG----TG or CG----CA transitions consistent with a chemical model of mutation via methylation-mediated deamination. This represents a 12-fold higher frequency than that predicted from random expectation, confirming that CG dinucleotides are indeed hotspots of mutation causing human genetic disease. However, since CG also appears hypermutable irrespective of methylation-mediated deamination, a second mechanism may also be involved in generating CG mutations. The spectrum of point mutations occurring outwith CG dinucleotides is also non-random, at both the mono- and dinucleotide, levels. An intrinsic bias in clinical detection was excluded since frequencies of specific amino acid substitutions did not correlate with the 'chemical difference' between the amino acids exchanged. Instead, a strong correlation was observed with the mutational spectrum predicted from the experimentally measured mispairing frequencies of vertebrate DNA polymerases alpha and beta in vitro. This correlation appears to be independent of any difference in the efficiency of enzymatic proofreading/mismatch-repair mechanisms but is consistent with a physical model of mutation through nucleotide misincorporation as a result of transient misalignment of bases at the replication fork. This model is further supported by an observed correlation between dinucleotide mutability and stability, possibly because transient misalignment must be stabilized long enough for misincorporation to occur. Since point mutations in human genes causing genetic disease neither arise by random error nor are independent of their local sequence environment, predictive models may be considered. We present a computer model (MUTPRED) based upon empirical data; it is designed to predict the location of point mutations within gene coding regions causing human genetic disease. The mutational spectrum predicted for the human factor IX gene was shown to resemble closely the observed spectrum of point mutations causing haemophilia B. Further, the model was able to predict successfully the rank order of disease prevalence and/or mutation rates associated with various human autosomal dominant and sex linked recessive conditions. Although still imperfect, this model nevertheless represents an initial attempt to relate the variable prevalence of human genetic disease to the mutability inherent in the nucleotide sequences of the underlying genes. PMID- 2192983 TI - [Post-menopausal metrorrhagia: endometrial ultrasonic aspects]. AB - Main causes of uterine post-menopausal bleeding are estrogenic substitutive therapy, ipo/atrophy, hyperplasia, carcinoma of endometrium and sarcoma. To evaluate the real usefulness of echotomography in these conditions, 128 patients in post-menopause (end of menstrual cycles from over an year) with at least one uterine bleeding were considered. The patients were submitted to pelvic ultrasonography in order to study uterine and ovarian morphology and, in particular, to examine endometrial echopattern. Endometrial reliefs were classified into 4 groups of echopattern and put in comparison with histopathology. From this comparison a well defined role of echotomography in the study of post-menopausal bleeding is evidenced: in cases of "abnormal echopattern" the probability of endometrial pathology is elevated (83.3%), with a good "sensibility" but without a so good "specificity" of ultrasounds: therefore its "subsidiary" but "necessary" role in the diagnosis of climateric uterine bleeding is emphasized. PMID- 2192984 TI - [Ultrasonics in the diagnosis and staging of endometrial carcinoma]. AB - In the study of endometrial pathology actually ultrasounds have a few utility in precocious diagnosis, but can be useful during the staging phase (echo histopathologic correlations, tumor biometry, myometrial invasion). Present study is relative to 134 patients affected by endometrial carcinoma (histologically proved) and preliminarily submitted to echotomography. The "false negative" results of ultrasounds were 16/134. Echographic observations, classified according to Niwa e coll. and Obata, were put in comparison with anatomo histopathology. The evaluations of tumor dimensions and myometrial invasion were correct respectively in 59.2% of cases and in 64.1% of cases. During the staging phase of endometrial neoplasia echotomography can allow a better pre-surgical definition, mainly with a more detailed informations about tumor biometry (T) and myometrial invasion (M). PMID- 2192985 TI - [Control of the emesis induced by cisplatin in patients with head and neck neoplasms. Randomized study of metoclopramide alizapride and placebo]. AB - A double blind study has been lead on 75 patients affected by head and neck cancer treated with CDDP, to verify the alizapride's antiemetic efficacy versus placebo and metoclopramide. On 76 patients examined, 28 has been treated with CDDP 50 mg/mq + alizapride; 28 with CDDP 50 mg/mq + metoclopramide and finally 19 with CDDP 50 mg/mq + placebo. Both alizapride and metoclopramide administered have resulted effective on the control of the emesis induced with CDDP without side effects. PMID- 2192986 TI - [Carcinoma of the male breast in the province of Alessandria. Clinico-pathologic aspects of an 8-years' case load]. AB - The authors report their experience on male breast carcinoma based on a series of 16 cases diagnosed between 1981 and 1988 at the City Hospital of Alessandria. Main clinico-pathological findings are described and compared with those recorded in the relevant world literature. Emphasis is placed on the immunohistochemical evaluation of estrogen receptors and the frequency data of this uncommon cancer in hospital-based series are reviewed. PMID- 2192987 TI - [Ultrasonics in the follow-up of cases of non-surgically treated endometrial carcinoma]. AB - Authors present an experimental study to evaluate the possibilities of ultrasounds in the follow-up of endometrial carcinoma inoperable cases. 18 women affected by endometrial adenocarcinoma (I or II stage F.I.G.O.) not submitted to surgery (due to increased surgical risk or refusal of operation) and treated by radio-hormonotherapy were considered. In these inoperable cases, echotomographic follow-up (in association to the usual oncologic specific follow-up) permitted to evaluate uterine modifications directly "in vivo": both for tumor dimensions and for myometrial invasion. Without reference to the effectiveness of radio-hormonal therapy, from our experience the utility of ultrasounds in the selection of "non responders" cases is evidenced ("non-responders" cases were then treated by chemotherapy). PMID- 2192989 TI - Water irrigating devices for the orthodontic patient. AB - Fixed orthodontic appliances increase the number of retention areas, resulting in increased possibilities for the accumulation of dental plaque. In addition, there is a risk of direct mechanical irritation. In spite of good toothcleaning most orthodontic patients develop generalized moderate gingivitis or an edematous type within one to two months after the placement of the fixed orthodontic appliances. Since the gingival changes represent a reaction to the bacterial plaque products rather than to the orthodontic forces; the only way to control them is by effective oral hygiene. Braces and banded teeth have many tiny recesses that a toothbrush and other cleaning aids have difficulty reaching. For good oral hygiene, these should be kept free of food debris. Water irrigating devices irrigates these hard-to-clean areas to remove food and other debris. Pulsating jets of water very gently lift the free gingiva to rinse out crevices. The water irrigator also pulses into areas between teeth and gums to flush out trapped food and debris. Water irrigating devices cannot by any means be regarded as substitutes for more effective plaque-removing methods, such as tooth-brushing and flossing; rather, they should be considered as an adjunct to the total oral hygiene program. PMID- 2192988 TI - A slide enzyme-linked immunosorbent assay (SELISA) for the diagnosis of Babesia bovis infections and for the screening of Babesia-specific monoclonal antibodies. AB - A slide enzyme-linked immunosorbent assay (SELISA), a modification of the standard ELISA technique, was developed for detection of Babesia bovis antibodies in bovine sera. Smears of B. bovis-infected blood were used as the source of antigen in the test which was read using a light microscope. Monoclonal antibodies to defined B. bovis antigens were used to demonstrate the cellular specificity of the test. The SELISA was shown to be as sensitive as existing non enzyme based serological tests for B. bovis. Comparative to the conventional ELISA technique, it was more economical and technically simpler, thus making it an ideal test for field application. PMID- 2192990 TI - The theoretical and practical application of a remoldable craniomandibular appliance. AB - This article introduces a new appliance for the orthopedic correction of craniofacial disorders. The development of a remoldable craniomandibular (RCM) appliance is the result of four years of clinical research. The remoldable craniomandibular appliance is designed as an inexpensive and time efficient method of arriving at a differential diagnosis for some patients with temporomandibular joint related headache. In addition, clinical observation indicates that it may be helpful in treatment for patients suffering from internal derangement of the temporomandibular joint. Although no specific claims for the appliance are being made at this time, research studies currently designed and implemented may be able to confirm the potential for this appliance. Independent studies are encouraged. PMID- 2192991 TI - Soft-tissue profile changes concurrent with the orthodontic treatment. AB - Anthropologists have shown that the external covering made up of integument, adipose tissue, connective tissue, and muscle does not always distribute itself in a uniform, orderly manner. There are great variations in the amount and distribution of these soft-tissue elements. Therefore, a facial profile analysis that is limited to measurements on the hard skeletal structure would not appear to conform to the standards of accuracy if an assessment of the soft-tissue profile were required. The purpose of this investigation is to provide an understanding of the changes which occur in the soft-tissue profile during the orthodontic treatment concurrent with normal growth and development. At the present time, it is not possible to devise a set rule for differentiating a desireable from an undesireable soft-tissue facial profile. However, this should not prohibit the presentation of some reference material as an aid in the diagnosis and practice of orthodontics. In many instances evaluations of facial esthetics seem to be singularly influenced by the orthodontist's concept of a pleasing face. At present, the accomplishment of soft-tissue profile changes by dental movement is limited so it is very important to rely on proper timing of the orthodontic treatment through the pubertal growth period to achieve optimal profile changes. PMID- 2192992 TI - No acquisition of metastatic capacity of R1H rhabdomyosarcoma upon transfection with c-Ha-ras oncogene. AB - The effect of the activated c-Ha-ras oncogene on invasiveness and formation of spontaneous metastases was studied using the rhabdomyosarcoma R1H of the rat. R1H tumor cells which are able to grow in vitro and produce tumors upon subcutaneous injection in syngeneic WAG/Rij rats were transfected with the c-Ha-ras (EJ) oncogene and the neomycin gene for selection. Two R1H cell lines harboring and expressing the human c-Ha-ras oncogene, one cell line containing the neomycin gene only, and the parent R1H cell line were compared. The expression of the transfected c-Ha-ras oncogene was assessed by Northern blot analysis and by flow cytometry using antibodies against ras p21. No difference in tumor growth rate and morphology was observed for the transfected and untransfected cell lines. Tumor volume doubling time was about 2 days in R1H-ras as well as in R1H parent tumors. Formation of spontaneous metastases was tested by excising the tumors when they had reached a volume of 2 cm3; after that the animals were observed up to 12 months. The excised tumors still contained and expressed the transfected ras oncogene as proved by Southern blot analysis and antibody staining using anti ras p21. In contrast to most previous work on ras-transfected tumorigenic cells the R1H-ras tumors did not acquire invasive growth potential or increased metastatic capacity. PMID- 2192993 TI - ras-transformed NIH 3T3 cell lines, selected for metastatic ability in chick embryos, have increased proportions of p21-expressing cells and are metastatic in nude mice. AB - We previously reported that ras-transformed NIH 3T3 cells could be selected in vivo for increased metastatic ability after intravenous injection into chick embryos, and that the metastatic cell populations expressed increased levels of ras p21 protein. We have tested the metastatic ability of a series of these cells in nude mice, to determine if their properties in the chick embryo experimental metastasis assay predict their metastatic behavior in nude mice. We report here that cells selected for metastatic ability in the chick embryo are also metastatic when assayed in nude mice. We also asked whether the selected cells uniformly expressed higher levels of p21, using an immunocytochemical procedure. We found that p21 expression among individual cells in these populations was quite heterogeneous. There was a direct relationship between the proportions of p21-expressing cells and metastatic ability in both assays, with increased proportions of p21-expressing cells in cell lines selected for metastatic ability. Our results suggest that (a) the experimental (i.v.) metastasis assay in the chick embryo offers an efficient and cost-effective procedure for the identification and selection of cells that are also experimentally metastatic in nude mice, and (b) the metastatic properties of ras-transformed NIH 3T3 cells are due to individual cells that express increased amounts of p21. PMID- 2192994 TI - Ectopic pituitary adenoma of the sphenoid sinus: report of a case and review of the literature. AB - Ectopic pituitary adenoma of the sphenoid sinus in a 68-year-old woman is presented. The confusing discrepancy between the imaging features and the mild clinical manifestations of extensive bone destruction of the skull base is emphasized. A definite diagnosis can be established only by histopathological examination supported by immunohistochemical studies. PMID- 2192996 TI - [The clinical spectrum of mastocytosis]. AB - Mastocytosis comprises a heterogeneous spectrum of clinical manifestations, extending from isolated, benign skin infiltrates to systemic involvement, occasionally with a fatal outcome. After a short survey of the morphology and physiology of the mast cell and the skin lesions of mastocytosis, the involvement of internal organs is reviewed and the differential diagnosis is discussed. The options for therapy are discussed, and the need for continuous monitoring of mastocytosis patients is emphasized. PMID- 2192995 TI - Evaluation of some prognostic factors in small squamous cell carcinoma of the mobile tongue: a multicenter study in Sweden. PMID- 2192997 TI - [Activated granulocytes as producers of reactive oxygen species--their significance for inflammatory reaction]. AB - The release of reactive oxygen species (ROS) by activated granulocytes is essential for the destruction of microbes and parasites in humans. Therefore, granulocytes play an important role in the pathogenesis of inflammatory reactions, particularly in inflammatory skin diseases. Besides their well-known toxic effects, ROS are capable of modulating a variety of different immune functions. The present review, therefore, focuses on the biological effects of ROS, on other producer cells of ROS besides granulocytes, on biochemical aspects of the production and interactions of ROS and on methods of detecting ROS production. Apart from well-known stimuli, which may be devoid of any physiological relevance or only induce a short-lived activation of granulocytes, cytokines are reported to induce a release of ROS. A possible modulatory effect of cytokines derived from immunocompetent and other cells on granulocyte activity could be of major importance for our understanding of the cellular interactions during inflammatory reactions, particularly in diseases characterized by granulocyte activation. The data presented allow a better understanding of the complex regulatory process of granulocyte activation in inflammatory skin diseases. PMID- 2192998 TI - [Satellite recurrence of eruptive angioma. A clinical, histologic and immunocytochemical study]. AB - Some weeks after operative removal of an eruptive angioma, satellite angiomas may develop within and around the scar. During the further course they remit spontaneously. So far these recurrences have been observed almost exclusively on the trunk in children and young adults, especially in male patients. Four new cases are reported. The course is consistent with earlier observations. Histologically, the cell proliferations follow the ramifications of afferent arteries. In older satellites, there are focal changes of intravascular papillary endothelial hyperplasia. These are interpreted as regression phenomena. Immunocytochemically, desmin-negative cells positive for muscle-actin are found in addition to endothelial cells. They are considered to be pericytes and myofibroblasts. Because of the close relationship with the afferent arterioles, disturbances in the vascular system are thought to be responsible for the development of angioma. If such underlying vascular disorders are not corrected by primary excision, satellite recurrences may occur. Because of their tendency to spontaneous remission, active therapeutic measures are not recommended. PMID- 2192999 TI - [Primary cutaneous plasmacytoma. A case report and review of the literature]. AB - Primary extramedullary plasmacytoma of the skin is a very rare disease; to our knowledge, only a few cases have been published in the world literature. In this paper, a patient who had a primary cutaneous plasmacytoma of the lower lip for 20 years is described. Serological, radiological and histological examinations excluded the possibility of an underlying multiple myeloma. The position of cutaneous plasmacytomas within the group of malignant plasma cell neoplasias is discussed and the relevant literature is reviewed. PMID- 2193000 TI - [Pseudolymphoma following tattooing]. AB - A single pseudolymphoma in the area of a tattoo is reported. Histological examination revealed an infiltrate composed of lymphocytes and histiocytes, and also confluent epithelioid cell aggregates without germinal centres. Immunohistologically, mainly T-lymphocytes and dendritic cells were demonstrable. PMID- 2193001 TI - Improved ultrasonic measurement techniques applied to assay of Pu and other transuranics in lung. AB - At the Lawrence Livermore National Laboratory, we are developing a system that will more accurately measure fat, muscle, and bone content from ultrasonic images of the chest wall. This paper describes a procedure that will allow chest-wall thickness to be determined to within +/- 1.5 mm (compared with the +/- 3-6 mm from current techniques) and may allow absolute errors in chest-wall composition to be reduced to +/- 4%. PMID- 2193003 TI - Low-dose radiation effects: interactions and synergism. AB - Experimental data from the author's laboratory are discussed, which demonstrate mutagenic and carcinogenic effects of low dose and low dose-rate exposure to ionizing radiation, and the modification of these effects by various chemical agents. These data are derived from studies of mutagenesis and neoplastic transformation in vitro, as well as on the induction of lung cancer in hamsters. On the basis of these results, several avenues of future research are suggested. These include: 1) the development and application of new human cell systems for studying radiation mutagenesis and transformation; 2) the study of the effects of protraction of exposure to radiation in such systems (emerging evidence suggests the dose-rate effect for mutagenesis may be minimal or absent in human cells); and 3) further examination of the role of secondary factors in radiation carcinogenesis. It appears unlikely that important information in these areas will arise from human epidemiologic studies. Knowledge derived from experimental systems should, however, enhance our understanding of the risks of radiation exposure and possible strategies to reduce them. PMID- 2193002 TI - Production and repair of DNA damage in mammalian cells. AB - Cellular genomes are continually subjected to endogenous and environmentally induced structural alterations. Our environment contains a multitude of substances that are carcinogenic and which, in many cases, are thought to act via direct damage to DNA. In order to better understand the consequences of DNA damage in cell killing and carcinogenesis, it will be important to: (a) develop new and sensitive techniques for the identification of specific types of DNA lesions; (b) examine what influence the function or activity of a DNA sequence has on the distribution of DNA damage within that DNA sequence and on its repair efficiency; (c) examine what influence the cell cycle has on the efficiency of DNA repair. PMID- 2193004 TI - Immunocytochemical demonstration of GAP-like immunoreactive neuronal elements in the human hypothalamus and pituitary. AB - GnRH-associated peptide (GAP)-like immunonreactive elements located in the human hypothalamus were investigated by PAP immunocytochemistry using specific antiserum against [pro-GnRH (14-69) OH]. Immunoreactive neuronal perikarya were distributed in the MPOA, PVN and infundibular nucleus, with the largest numbers of GAP-like immunoreactive perikarya found in the infundibular nucleus. We also detected the coexistence of GAP-like and GnRH-like immunoreactivities in the same neuronal perikarya in the MPOA by using a double immunolabelling procedure. In addition to the above regions immunoreactive neuronal perikarya were present in the region dorsal to the medial mammillary nucleus. GAP-like immunoreactive fibers were distributed in same areas that immunoreactive perikarya were observed. Many immunoreactive terminals were found adjacent to capillaries in the infundibulum. Immunoreactive dots, presumably terminals, were observed in the posterior pituitary and these were particularly evident along the margin adjacent to the anterior pituitary. The distribution pattern and density of GAP-like immunoreactive neuronal elements are compared with those of other mammalian species. We also compared GAP-like immunoreactive elements with that of GnRH as has been previously observed in the human hypothalamus. PMID- 2193006 TI - [Angioneurotic edema of the tongue, induced by administration of ACE inhibitors]. AB - Inhibitors of angiotensin converting enzyme can rarely cause an angioneurotic edema of the upper airways. This complication depends on the interaction with hormones regulating the vascular resistance such as the kallikrein kinin and the prostaglandin systems. We present two cases of angioneurotic edema of the tongue induced by inhibitors of angiotensin converting enzyme. We describe the symptoms of this side effect and discuss possible therapeutic approaches. PMID- 2193005 TI - The antigen of bile canaliculi of the mouse hepatocyte: identification and ultrastructural localization. AB - The AgB10 antigen of bile canaliculi of the mouse hepatocyte was identified using monoclonal antibodies. The Mr value of 116000 for AgB10 was measured by immunoblotting. The tissue localization of AgB10 was studied by light and electron microscopy using the immunoperoxidase technique. AgB10 was predominantly present on the microvillus membrane of bile canaliculi, the brush border of intestinal mucosa and apical surfaces of the epithelial cells in some other organs. A small amount of AgB10 was detected on the basolateral domain of the hepatocytes. AgB10 was specific for hepatocytes and was not found in the other cell types of the liver. In primary hepatocyte culture, AgB10 was localized on the surface of cells during the first 24 h, predominantly at the sites of cell cell and cell-substratum contacts. After 48 h of culture AgB10 gradually disappeared from contacting cell surfaces and became concentrated only in the reconstituted bile canaliculi. PMID- 2193007 TI - [Diagnosis of carotid body tumor by imaging procedures]. AB - The imaging techniques available for the diagnosis of tumors of the glomus caroticum are discussed with reference to four cases (three patients, one with tumor bilaterally). Taking into consideration the practicability and invasiveness of the investigations as well as the risks and costs involved, we propose that the procedures be performed in the following sequence: ultrasonography, Doppler ultrasonography, computed tomography (CT) or (even better) magnetic resonance imaging (MRI), and selective angiography. In most cases where there is a non inflammatory mass in the neck, ultrasonography and Doppler ultrasonography may be adequate to establish the diagnosis of a glomus caroticum tumor. B-scan ultrasonography reveals an inhomogeneous mass that pushes the carotid arteries apart and an arteriovenous shunt may be seen using the Doppler technique. CT and MRI show the full extent of the tumor and provide information about infiltration of adjacent structures. Selective intra-arterial angiography confirms the diagnosis, demonstrating a profound vascularized tumor in the carotid bifurcation. If angiography leads to identification of an afferent vessel, selective embolization of the tumor may be performed, thus enabling a much safer operation with less blood loss. PMID- 2193008 TI - FR112123, a new oligopeptide antibiotic from Streptomyces viridochromogenes. Taxonomy, fermentation, isolation, physico-chemical properties, structure and biological activity. AB - FR112123 is a new oligopeptide antibiotic produced by Streptomyces viridochromogenes No. 7587. The structure of FR112123 is elucidated as N-(N6-(N2 glycyl-L-glutaminyl)-D-lysyl)-D-alanine (1) by spectroscopic and chemical evidence. It resembles a partial structure of peptidoglycan in bacteria. The compound has a superior activity against an Escherichia coli mutant sensitive to inhibitors of cell wall synthesis, although it has a weak activity against the parent strain. These suggest that FR112123 might act on the biosynthesis of bacterial cell wall. PMID- 2193009 TI - Synthesis and structure determination of FR109615, a new antifungal antibiotic. AB - The structure of FR109615, a new antifungal antibiotic, was determined to be (1R,2S)-2-aminocyclopentane-1-carboxylic acid ((-)-cis-2-ACPC: 8a) by X-ray analysis. (-)-cis-2-ACPC (8a) was also synthesized via optical resolution of 3a and 3b derived from (+/-)-cis-2-ACPC hydrochloride (1). 8a showed potent antifungal activity, while its antipode (+)-cis-2-ACPC (8b) had no activity. PMID- 2193010 TI - Fetal tectum grafted as a cell suspension into the adult rat inferior colliculus. AB - The known structural and functional features of the inferior colliculus provided an advantageous substrate for examining the outcome of neural transplantation. In the present study, tissue from the midbrain tectum of Sprague-Dawley rat fetuses was removed at 15, 16 and 19 days of gestation (E15, E16 and E19), incubated as a dissociated cell suspension for 12 to 15 h in a medium containing True Blue for prelabeling, and injected into the central nucleus of the inferior colliculus (CNIC) of 28 normal male adult conspecifics. Viable tectal grafts were found in 57.5% of host animals with 65.2% located in CNIC. Grafts of E16 tissue had a survival rate of 84.2%, which was twice that of E15 or E19 donors, and there was no difference in graft survival rate in hosts sacrificed up to 6 months after the implantation procedure. Neurons prelabeled with True Blue and counterstained with thionin were identified as uniquely green stained cells in brightfield illumination and brilliant opaque cells in darkfield microscopy. Grafts were organized in tightly packed clusters of cells including large rounded polygonal and smaller cells similar in size to normal CNIC large and small multipolar neurons. Cell morphology of the larger ovoid and fusiform grafted neurons most closely resembled that of typical adult CNIC cell populations; other implanted cell types appeared immature even when host post-implant survival was extended. At longer post-implant intervals graft and host cells further intermingled, and both cellular and fibrous bridges were observed at the interface between host and graft tissue. The present work demonstrates the viability and development of homotypic cells grafted into a central auditory structure utilizing a simple method of prelabeling donor tissue with a fluorescent dye. PMID- 2193012 TI - Allogeneic bone marrow transplantation for acute leukemia. AB - Allogeneic marrow transplantation has emerged as a curative therapy for many patients with acute leukemia. The ability to cure patients of their disease is dependent on the remission status of the patient. For patients with acute myelogenous leukemia, up to 60% of patients can become long-term, disease-free survivors, whereas a similar number of patients with high-risk acute lymphoblastic leukemia can also achieve cure of their disease. The improved results with marrow transplantation have allowed the application of this therapy for patients up to the age of 50 years. Even patients with therapy-related leukemias can benefit from this approach. Although relapse is still a problem in all remission stages, current studies suggest that improved preparatory regimens, in combination with better treatment of graft-versus-host disease and prevention of cytomegalovirus pneumonia, will continue to improve the overall results of this therapy for patients with acute leukemia. PMID- 2193011 TI - The HLA system in clinical marrow transplantation. AB - The HLA system is comprised of more than 30 class I and class II genes that encode a polymorphic array of cell-surface glycoprotein molecules that function to restrict or direct the specificity of T-cell responses. Class I alloantigens, encoded by HLA-A, -B, and -C genes, historically have been identified and characterized by the use of alloantisera. Three additional class I genes, HLA-E, F, and -G, have been identified recently, but it is not known yet if these are relevant to transplantation. The demonstration of further polymorphism among class I alleles, however, has been made possible by the use of cytotoxic lymphocytes and by isoelectric focusing gel electrophoresis. Class II alloantigens, encoded by DR, DQ, and DP genes residing in the HLA-D region, can be defined both serologically and by the use of cellular reagents. Recent advances in DNA typing methods, including restriction fragment length polymorphism and sequence-specific oligonucleotide probe analysis, provide tools which more completely define the extent of HLA polymorphism within given populations. The diversity of allelic variation within the HLA system, coupled with the fundamental role of class I and class II molecules in the triggering of allograft reactions, necessitates the continuing improvement of techniques for characterizing distinct HLA molecules and providing for the better matching of donor and recipient prior to allotransplantation. PMID- 2193013 TI - Treatment of chronic myelogenous leukemia with bone marrow transplantation. AB - BMT is the only curative therapy for CML, a uniformly lethal malignant disorder of the hematopoietic stem cell. Younger patient age and transplant in CP are associated with better outcome. Transplant within 1 year of diagnosis may provide a greater chance of survival than transplant at a longer interval from diagnosis. T-cell depletion of donor BM significantly reduces the incidence of acute and chronic GVHD, but is associated with an increased risk of graft failure and a marked increase in rate of relapse. Early results suggest that HLA-matched or partially HLA-mismatched unrelated donors may be used successfully in cases in which a suitably matched related donor is not available. Autologous transplantation of BM or PB stem cells can result in successful engraftment and possibly prolonged survival in some patients with CML. Following allogeneic BMT, some patients relapse cytogenetically without progressing to hematologic relapse. The use of PCR methodology to amplify bcr-abl transcripts has revealed persistence of the malignant clone in a substantial number of patients who are in hematologic and cytogenetic remission. The clinical significance and biologic mechanism(s) of this form of molecular relapse remain to be defined. PMID- 2193014 TI - Treatment of aplastic anemia. AB - Survival of patients with aplastic anemia after immunosuppressive therapy with ATG/ALG ranges from 35% to 60%. However, long-term follow-up on these patients has indicated a high frequency of hematologic complications, including PNH, myelodysplasia, ANL, and recurrent aplasia. In contrast to immunosuppressive therapy, allogeneic marrow transplantation results in cure of aplasia. Problems initially limiting the success of HLA-matched allogeneic marrow transplants included graft rejection and complications associated with acute and chronic GVHD. Infusion of donor buffy coat cells along with marrow or alternatively more intensive immunosuppressive regimens containing irradiation have substantially decreased the risk of rejection. However, buffy coat infusion increases the incidence of chronic GVHD and irradiation treatment adds to toxicity of the conditioning regimen as well as producing long-term complications. The incidence and severity of acute GVHD have been significantly decreased by the use of MTX/CSP as GVHD prophylaxis; however, this regimen has had no impact on the incidence of chronic GVHD. Long-term survival in multiply transfused patients after HLA-identical marrow transplantation is on the order of 60% to 70%; survival in untransfused patients approximates 80%. Patients less than age 18 transplanted on protocols currently active in Seattle have greater than 90% survival. Further increases in survival must come from improvement in preventing and treating chronic GVHD. Patients diagnosed with aplastic anemia should have rapid HLA typing performed to identify possible marrow donors. Transfusions from prospective marrow donors should be avoided and the patient referred to a major treatment center. We continue to recommend allogeneic marrow transplantation for patients with severe aplastic anemia who are less than 40 years old and who have HLA-identical related donors. Immunosuppressive therapy should be tried first in patients without HLA-matched donors and for patients over the age of 40. HLA mismatched marrow transplantation and use of unrelated marrow donors for severe aplastic anemia remain areas of active research. PMID- 2193015 TI - Graft-versus-host disease. AB - Graft-versus-host disease (GVHD) is caused by immunologic recognition of the patient by the donor marrow graft after allogeneic bone marrow transplantation. Despite advances in understanding and new agents and methods to treat GVHD, the disease and complications related to it and its treatment are the principal causes of death after transplantation. This article reviews the pathogenesis, prediction, prophylaxis, and treatment of both acute and chronic GVHD. PMID- 2193016 TI - Delayed complications and long-term effects after bone marrow transplantation. AB - Bone marrow transplantation is being used with increasing frequency and success for an expanding number of indications. At present, more than 1000 patients are surviving more than 5 years and several hundred more than 10 years after transplantation. Extended observation periods have shown that numerous complications have to be expected in these patients, particularly in those given TBI as part of the conditioning regimen. However, other factors including chemotherapy, GVHD, viral infections, host environment, and genetic factors also contribute to the problem. It has been pointed out by critics of bone marrow transplantation that success is often reported as disease-free survival, meaning survival in remission. However, there are, obviously, secondary problems that can significantly impair patients' quality of life, even though their leukemia (or lymphoma) is in unmaintained remission. Very few data on quality of life in long term surviving patients have been reported. Several studies are currently ongoing (Forman S, Blume K, personal communication), and the results are urgently needed. It will also be of interest to compare patients given, allogeneic transplants with those given autologous marrow infusions in an attempt to determine to what extent conditioning regimens and alloreactivity contribute to long-term side effects. It will be even more important to design regimens that are less likely to induce these problems and to design therapeutic approaches to treat complications effectively. PMID- 2193017 TI - Immune recovery after bone marrow transplantation. AB - The donor-derived immune system that forms after bone marrow transplantation (BMT) takes as long as 2 years to develop in healthy BMT recipients. Soon after BMT, GVHD and its treatment increase the susceptibility of the recipient to overwhelming infections, and they retard the development of the immune system. The new system develops from a primitive state characterized by cytotoxic and suppressive functions and progresses to a mature state characterized by the development of specialized lymphocyte functions such as lymphokine production, proliferation, and expression of growth factor receptors. These specialized functions develop in healthy long-term recipients, whereas the same functions may be absent or impaired in those who develop chronic GVHD. PMID- 2193018 TI - Marrow transplantation from donors other than HLA identical siblings. AB - As marrow transplantation has become the treatment of choice for many hematologic diseases, the lack of HLA-matched family donors has become a critical issue. With the advancement of histocompatibility testing technology, it has become possible to begin defining those genetic determinants that are important to a successful transplant, and begin exploring the use of related donors who are not fully HLA matched, and unrelated donors, HLA matched or not. Given the early encouraging data, it appears likely that a substantial number of patients will benefit from the use of such alternative donors. PMID- 2193019 TI - T-cell depletion to prevent graft-versus-host disease after bone marrow transplantation. AB - Graft-versus-host disease (GVHD) remains a major obstacle to successful bone marrow transplantation. Depletion of T lymphocytes from the donor marrow prior to transplantation substantially reduces the morbidity and mortality due to acute and chronic GVHD. Unfortunately, graft failure, usually due to rejection and leukemia relapse, are adversely affected by this approach. This article reviews current techniques for T-cell depletion and results of recent clinical trials directed to overcome major problem areas. PMID- 2193020 TI - Psychodynamic themes of bone marrow transplantation. When I becomes thou. AB - In-depth psychodynamic factors about bone marrow transplantation are described. These factors are related to the BMT recipient, donor, recipient's family, and hospital staff. The emphasis is on the meaning of the experience emotionally and symbolically for the participants in BMT. PMID- 2193021 TI - Terminally differentiating epithelial tissues in primary explant culture: a model of growth and development. AB - Many epithelial tissues are characterized by the presence of basal cells which serve the dual roles of self-renewal and of progression through terminal differentiation, to a functional state. Such tissues, when grown in vitro as primary explants, exhibit a characteristic pattern of outgrowth and development which includes both renewal and efforts toward normal differentiation. The degree of differentiation achieved depends upon conditions of culture and may be modulated in a variety of ways. The human prostate constitutes such a system and offers numerous possibilities for investigating basic control mechanisms in growth and development. Information on a variety of epithelial tissues is reviewed and experimental results using human prostate tissue are presented. PMID- 2193022 TI - Antibody against the C-terminal portion of dystrophin crossreacts with the 400 kDa protein in the pia mater of dystrophin-deficient mdx mouse brain. AB - The mdx mouse is an animal model for X-linked Duchenne muscular dystrophy. A polyclonal antibody against a synthetic peptide IV equivalent to the C-terminal portion (amino acids 3495-3544) of dystrophin crossreacted with a 400 kDa protein in the brain and the spinal cord of mdx mouse, as well as in the control B10 mouse. However, the protein did not crossreact with the polyclonal antibody raised against the N-terminal portion of dystrophin peptide I (amino acids 215 264). Immunofluorescent micrography revealed that the outside of the small arteries and the pia mater of the brain strongly reacted with the anti-peptide IV antibody. These results strongly suggest the presence of a crossreactive protein other than dystrophin, possibly a dystrophin-related autosomal gene product, in the pia mater. PMID- 2193023 TI - Regulation of L-type pyruvate kinase gene expression by dietary fructose in normal and diabetic rats. AB - Previous studies have shown that dietary fructose stimulates expression of the L type pyruvate kinase gene mainly at the post-transcriptional level in diabetic liver, and that this effect may be mediated by a metabolite common to both fructose and glycerol. In the present work, we carried out further studies on the mechanism of fructose induction of L-type isozyme mRNA in the liver, kidney and small intestine of rats. The L-type isozyme mRNA in the kidney of normal and diabetic rats was increased by dietary fructose, the time course of the increase being similar to that observed in the small intestine and liver. The mRNA was not induced in the kidney by dietary glucose or insulin. Glycerol was also a potent inducer of the mRNA in the kidney and liver, but not in the small intestine. These results show that fructose and glycerol induced increase in the mRNA only in organs in which they were metabolized, and thus support the metabolite hypothesis. No other carbohydrates tested increased the level of mRNA in these tissues, except glucose, which increased the level in the small intestine. Thus a molecule that increase the mRNA level may accumulate significantly during metabolism of only certain carbohydrates. Dietary fructose or glycerol slightly stimulated transcription of the gene for the L-type isozyme in diabetic liver, and also in normal and diabetic kidney, but the magnitudes of increase were much lower than those of the mRNA, confirming our previous findings described above. On the other hand, dietary fructose caused marked stimulation of gene transcription in normal rat liver, although the magnitude of its induction of the mRNA was similar to that in diabetic liver. Insulin treatment of fructose-fed diabetic rats also caused a marked increase in the gene transcription without any concomitant change in the mRNA level. Thus, the mechanism of fructose induction of the L-type pyruvate kinase in diabetic liver, which is similar to that found in the kidney, is different from that in normal liver, and this difference is attributable to the difference in the level of insulin. PMID- 2193024 TI - Positive control. PMID- 2193025 TI - In the absence of a downstream element, the apolipoprotein E gene is expressed at high levels in kidneys of transgenic mice. AB - Human apolipoprotein (apo) E gene constructs with 30 or 5 kilobases of 5' flanking and 1.5 kilobases of 3'-flanking regions were used to create transgenic mice. High levels of human apoE mRNA were present in the transgenic kidney, but none was detected in the liver, which is normally the major source of apoE. When a construct with 5 kilobases of 5'- and 23 kilobases of 3'-flanking regions was used, only trace levels of human apoE mRNA were detected in the kidney, whereas high levels were found in the liver. These results indicated that regulatory elements downstream of the human apoE gene interacted with the transcription initiation complex to stimulate gene expression in the liver while suppressing expression in the kidney. In each case, human apoE was secreted into the plasma. The source of human apoE in the transgenic kidney was the epithelial cells lining the proximal tubule and Bowman's capsule. PMID- 2193026 TI - Yeast KEX1 protease cleaves a prohormone processing intermediate in mammalian cells. AB - A vaccinia virus vector was used to express the yeast KEX1 gene, which encodes a prohormone carboxypeptidase specific for the removal of basic amino acids from prohormone processing intermediates, in mammalian cells. When produced in BSC-40 cells, Kex1p was localized to the perinuclear region and conferred a large increase in enzymatic activity characteristic of this carboxypeptidase. Expression of the KEX1 gene together with the yeast KEX2 gene, which encodes a prohormone endopeptidase specific for cleavage at pairs of basic amino acids, and the mouse proopiomelanocortin (mPOMC) cDNA in BSC-40 cells resulted in the full conversion of mPOMC to mature peptides including gamma-lipotropin. This in vivo processing of mPOMC to mature peptides by the KEX2/KEX1 gene products demonstrates a significant functional homology of the basic prohormone processing machinery in yeast and neuroendocrine cells. PMID- 2193027 TI - Active site labeling of the shikimate pathway enzyme, dehydroquinase. Evidence for a common substrate binding site within dehydroquinase and dehydroquinate synthase. AB - Dehydroquinase, the third enzyme of the shikimate biosynthetic pathway, is inactivated by iodoacetate. Iodoacetate behaves as an affinity label for the Escherichia coli enzyme with a Ki of 30 mM and a limiting inactivation rate of 0.014 min-1 at pH 7.0 and 25 degrees C. Affinity labeling is mediated by the negative charge of the reagent since iodoacetamide does not inactivate the enzyme. 2.1-2.3 mol of carboxymethyl groups are incorporated per mol of protein monomer resulting in 90% inactivation of enzymic activity. The majority of the bound label (80%) is split equally between 2 methionine residues, Met-23 and Met 205, which were identified by sequencing radiolabelled peptide fragments isolated after proteolytic digestion. An equilibrium mixture of the substrate (dehydroquinate) and product (dehydroshikimate) substantially reduces the inactivation rate and specifically decreases the incorporation of label at both of these site, implicating them as being in or near the active site of the enzyme. Sequence alignments with other biosynthetic dehydroquinases show that of the 2 methionine residues only Met-205 is conserved. N-terminal alignments of all the available dehydroquinase sequences (both catabolic and biosynthetic classes) revealed that Met-23, although itself not conserved, resides within a cluster of conserved sequence which may constitute part of the dehydroquinate binding site. A consensus sequence was derived from these alignments and used to probe the protein sequence data banks. A related sequence was found in dehydroquinate synthase, the enzyme which precedes dehydroquinase in the shikimate pathway. These results suggest that we have identified part of the dehydroquinate binding site in both enzymes. PMID- 2193028 TI - Reversible alkylation of an active site methionine residue in dehydroquinase. AB - Iodoacetic acid inactivates dehydroquinase by simultaneously alkylating 2 methionine residues (Met-23 and Met-205), presumed to be active site residues (described in Kleanthous, C., Campbell, D. G., and Coggins, J. R. (1990) J. Biol. Chem. 265, 10929-10934). Although both sites are carboxymethylated to the same degree in the inactivated enzyme, the modification of Met-205 may be reversed by treatment with mercaptoethanol at alkaline pH, as shown by the stoichiometric loss of label from this site. This, in turn, leads to partial reactivation of the inactive enzyme. Alkylation of Met-23 is not reversible under these conditions. The chemistry of the cleavage reaction at Met-205 was investigated by isolating the cleavage product which was identified by mass spectrometry as the ammonium salt of 2-hydroxyethyl thioacetate. This result is consistent with nucleophilic attack by the thiolate anion of mercaptoethanol on the alpha-carbon of the carboxymethyl moiety, which restores the side chain of the methionine residue (Met-205) and liberates 2-hydroxyethyl thioacetate. The differential reactivity of the 2 carboxymethylated methionine residues toward mercaptoethanol is likely to be a reflection of their different microenvironments in the folded protein. This assertion is borne out by unfolding experiments which indicate that neither of the carboxymethylated methionine residues in dicarboxymethylated dehydroquinase is susceptible to mercaptoethanol cleavage if the protein is first denatured by either guanidine hydrochloride or urea. Furthermore, this denatured material refolds after removal of denaturant to yield protein with reactivation properties similar to untreated, dicarboxymethylated enzyme. PMID- 2193029 TI - Characterization of crystalline rat liver fatty acid binding protein produced in Escherichia coli. AB - The principal absorptive cell of the rat small intestinal epithelium contains two homologous cytosolic proteins that bind long chain fatty acids. These are known as intestinal and liver fatty acid binding proteins (FABP). While their precise physiological roles have not been defined, they are believed to represent a multifunctional cytosolic transport system that is involved in the trafficking of exogenous lipids to sites of metabolic processing. 13C NMR studies have revealed differences in their fatty acid binding stoichiometries, binding mechanisms, and the ionization properties of bound fatty acids. To understand the functional differences, liver FABP has been crystallized for eventual comparison with the known crystal structure of intestinal FABP. The lattice type is trigonal with unit cell dimensions of a = b = 84.1 A and c = 44.2 A. The space group as determined by examination of the Patterson symmetry is either P3(1)21 or P3(2)21. PMID- 2193030 TI - Expression and secretion of Mirabilis antiviral protein in Escherichia coli and its inhibition of in vitro eukaryotic and prokaryotic protein synthesis. AB - Mirabilis antiviral protein (MAP), a ribosome-inactivating protein, exhibits inhibitory effects on both plant virus infection and protein synthesis. To study these functions by site-specific mutagenesis, the total synthetic gene of MAP was constructed and expressed in Escherichia coli. However, the growth of the host was inhibited by the products, and the yield of MAP was very low. To improve the system for expressing MAP, an expression vector, pSH7, was constructed. This vector is based on the high copy number plasmid pUC19 and includes PL promoter and temperature-sensitive cI857 repressor. The plasmid also contains the ompA signal sequence and the total synthetic MAP gene. The MAP gene was expressed and its product was secreted into the culture medium after E. coli transformants were cultivated at 30 degrees C and the temperature was raised to 42 degrees C. The secreted MAP was then purified and characterized. This protein was identical to native MAP as determined by its mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the amino acid sequence at the NH2 terminus, and its inhibitory effect on in vitro protein synthesis. MAP was found to inhibit the in vitro protein synthesis of rabbit reticulocyte and wheat germ. It further showed an IC50 concentration of approximately 200 nM in an E. coli in vitro translation system in contrast to ricin A-chain, a well known ribosome-inactivating protein. PMID- 2193031 TI - Mitochondrial precursor protein. Effects of 70-kilodalton heat shock protein on polypeptide folding, aggregation, and import competence. AB - A hybrid precursor protein constructed by fusing the mitochondrial matrix targeting signal of rat preornithine carbamyl transferase to murine cytosolic dihydrofolate reductase (designated pO-DHFR) was expressed in Escherichia coli. Following purification under denaturing conditions, pO-DHFR was capable of membrane translocation when diluted directly into import medium containing purified mitochondria but lacking cytosolic extracts. This import competence was lost with time, however, when the precursor was diluted and preincubated in medium lacking mitochondria, unless cytosolic proteins (provided by rabbit reticulocyte lysate) were present. Identical results were obtained for purified precursor made by in vitro translation. The ability of the cytosolic proteins to maintain the purified precursor in an import-competent state was sensitive to protease, N-ethylmaleimide (NEM), and was heat labile. Further, this activity appeared to be signal sequence dependent. ATP was not required for the maintenance of pO-DHFR competence, nor did purified 70-kDa heat shock protein (the constitutive form of Hsp70) substitute for this activity. Interestingly, however, purified Hsp70 prevented aggregation of the precursor in an ATP dependent manner and, as well, retarded the apparent rate and extent of pO-DHFR folding. Partial purification of reticulocyte lysate proteins indicated that competence activity resides within a large mass protein fraction (200-250 kDa) that contains Hsp70. Sucrose density gradient analysis revealed that pO-DHFR reversibly interacts with components of this fraction. Pretreatment of the fraction with NEM, however, significantly stabilized the subsequent formation of a complex with the precursor. The results indicate that Hsp70 can retard precursor polypeptide folding and prevent precursor aggregation; however, by itself, Hsp70 cannot confer import competence to pO-DHFR. Maintenance of import competence correlates with interactions between the precursor and an NEM sensitive cytosolic protein fraction. Efficient dissociation of the precursor from this complex appears to require a reactive thiol moiety on the cytosolic protein(s). PMID- 2193032 TI - Resolution of factors required for the initiation of transcription by yeast RNA polymerase II. AB - Fractionation of a yeast nuclear extract reveals at least four factors required in addition to RNA polymerase II for accurate initiation of transcription. One of these factors can be replaced by HeLa transcription factor IID or by its yeast counterpart expressed in Escherichia coli. Each of the remaining three factors can be replaced by a fraction from yeast whole cell extract, facilitating further purification of the factors. PMID- 2193033 TI - Functional interaction between the herpes simplex-1 DNA polymerase and UL42 protein. AB - The herpes simplex virus 1 (HSV-1) UL42 protein, one of seven herpes-encoded polypeptides that are required for the replication of the HSV-1 genome, is found in a 1:1 complex with the HSV-1 DNA polymerase (Crute, J. J., and Lehman, I. R. (1989) J. Biol. Chem. 264, 19266-19270). To obtain herpes DNA polymerase free of UL42 protein, we have cloned and overexpressed the Pol gene in a recombinant baculovirus vector and purified the recombinant DNA polymerase to near homogeneity. Replication of singly primed M13mp18 single-stranded DNA by the recombinant enzyme in the presence of the herpes encoded single-stranded DNA binding protein ICP8 yields in addition to some full-length product a distribution of intermediate length products by a quasi-processive mode of deoxynucleotide polymerization. Addition of the purified UL42 protein results in completely processive polymerization and the generation of full-length products. Similar processivity is observed with the HSV-1 DNA polymerase purified from herpes-infected Vero cells. Processive DNA replication by the DNA polymerase isolated from HSV-1-infected Vero cells or the recombinant DNA polymerase-UL42 protein complex requires that the single-stranded DNA be coated with saturating levels of ICP8. ICP8 which binds single-stranded DNA in a highly cooperative manner is presumably required to melt out regions of secondary structure in the single-stranded DNA template, thereby potentiating the processivity enhancing action of the UL42 protein. PMID- 2193034 TI - HSP 70 gene expression in Trypanosoma cruzi is regulated at different levels. AB - The level of HSP 70 mRNA is altered in Trypanosoma cruzi cells incubated at supra optimal temperatures: the total amount of this RNA per cell is increased at 37 degrees C, and slightly decreased at 40 degrees C relative to its level at 29 degrees C. However, its amount is greater in the polysomes at either temperature. The relative increase of this RNA is larger in the polysomes fraction than it is in the total RNA. In addition the level of HSP 70 protein in heat-shocked cells is greater than would be expected from the recruitment of HSP 70 mRNA in the polysomal fraction. Taken together the data are interpreted as indicating that at 37 degrees C and 40 degrees C the HSP 70 gene regulation in T. cruzi involves both the selective accumulation of the HSP 70 mRNA in the polysomes and its preferential translation. At 37 degrees C, in addition, an increase in the total amount of this template is observed in the cells. PMID- 2193035 TI - Insulin-like growth factor-1 (IGF-1), insulin, and epidermal growth factor (EGF) are survival factors for density-inhibited, quiescent Balb/c-3T3 murine fibroblasts. AB - The great majority of murine Balb/c-3T3 fibroblasts in density-inhibited, quiescent cultures disintegrate and die rapidly when cells are deprived of serum in the medium. Platelet-derived growth factor (PDGF, 5 ng/ml) used alone and insulin-like growth factor (IGF-1, 40 ng/ml) + epidermal growth factor (EGF, 10 ng/ml) prevent most of this cell death and all three factors used together protect close to all cells in the confluent monolayer as determined by counting trypsinized cell suspensions in a Coulter counter. IGF-1 used alone affords a high level of protection during the first 5 hours of incubation in serum-free medium but the protective effect declines subsequently unless EGF is also present. EGF alone has little protective activity. The survival-promoting activity of PDGF used alone or of PDGF + EGF + IGF-1 is not significantly decreased by selective inhibition of messenger precursor RNA transcription with 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole (DRB, 20 or 40 microM), which prevents G1 traverse of the cells mediated by the combination of the three growth factors. DRB also does not interfere with the early protective effect of IGF-1 + EGF, but decreases the late protective effect of this growth factor combination. DRB by itself decreases cell viability in the absence of growth factors or serum. In these experiments viability was assayed by neutral red uptake by using an automated microplate reader. Inhibition of protein synthesis with cycloheximide (CHX, 1 or 5 micrograms/ml) over a 20-hour period was associated with decreased survival of cells protected by IGF-1 + EGF or PDGF + EGF + IGF, but also with decreased survival of cells incubated in the absence of growth factors or serum. The decrease in survival was somewhat more marked when IGF + EGF was present than when PDGF + EGF + IGF-1 was present. Insulin (1,500 ng/ml) mimics the action of IGF-1 (40 ng/ml). The cell survival-enhancing activities of growth factors are concentration dependent. The evidence presented indicates that PDGF, EGF, and IGF 1 (or insulin) act through distinctive mechanisms in affording protection of cells against death. The short-term protective effects of the growth factors are independent of gene expression and may be mediated via metabolic events. Long term protection may be dependent on gene expression, especially in the case of IGF-1 + EGF. PMID- 2193036 TI - Accuracy of sonography in transient synovitis. AB - The presence of acute transient synovitis (TS, irritable hip) often warrants hospital admission not only to exclude underlying sepsis but also to aspirate when the intraarticular pressure might induce ischemia in the femoral head. Diagnostic doubt may affect this admission. We evaluated 68 patients in a prospective study comparing sonography with diagnostic aspiration and clinical examination. Sonography proved to be relatively accurate (81%) but was inferior to careful clinical evaluation in diagnosing hip effusions. Sonography may be helpful if diagnostic doubt exists. Aspiration under sonographic control will improve this accuracy. PMID- 2193037 TI - Lower positional deformity in infants and children: a review. PMID- 2193038 TI - Primary palatorraphy in the adult cleft palate patient. Surgical, prosthetic and logopaedic aspects. AB - The treatment of 8 adults with untreated cleft palates is retrospectively discussed. A palatorraphy, consisting of a palatoplasty with pedicled palatal mucoperiosteal flaps and an intravelar veloplasty, is performed. A rib graft between the nasal and oral layer and a partial vestibuloplasty are used in a few patients to create a more favourable anatomical situation for the prosthetic appliance. The palatorraphy contributes to improved speech intelligibility however, combined with a pharyngeal flap as performed in 5 patients, an even better result can be achieved. According to the results, a surgical procedure in the adult still seems to be worthwhile. PMID- 2193039 TI - Rhinological manifestations of Paget's disease of bone (Osteitis deformans). AB - Two cases of Paget's disease of bone are presented in which nasal symptoms were prominent. The clinical and radiographic features of Paget's disease of the maxilla and ethmoids are described. Medical and surgical treatment is discussed with the recommendation that surgery is kept to a minimum and covered by prophylactic antibiotics to prevent osteomyelitis. Sudden enlargement of the involved bones should raise the suspicion of malignancy. PMID- 2193040 TI - Synaptology of luteinizing hormone-releasing hormone (LHRH)-immunoreactive cells in the nervus terminalis of the gray short-tailed opossum (Monodelphis domestica). AB - Light and electron microscopic immunocytochemistry were used to examine the structure of LHRH neurons and fibers in the nervus terminalis of the gray short tailed opossum (Monodelphis domestica). LHRH-immunoreactive neurons and fibers form a loose plexus within the fascicular network of the ganglion terminale on the median surface of the olfactory bulb. There are at least two populations of LHRH-immunoreactive neurons within the network of the ganglion terminale: fusiform and round neurons similar to those described in the forebrain. At the ultrastructural level, axosomatic and axodendritic contacts were seen between LHRH-immunoreactive and nonimmunoreactive elements in the ganglion terminale. These contacts were classified as 1) synaptic input, with asymmetric synapses seen between a nonimmunoreactive axon terminal and a LHRH-immunoreactive cell body or a nonimmunoreactive axon terminal and a LHRH-immunoreactive dendritic process. 2) synaptic output, with symmetric synapses seen between LHRH immunoreactive and nonimmunoreactive processes. This study is the first systematic examination of the ultrastructure of the LHRH-immunoreactive neurons and their synaptic contacts in the nervus terminalis. The possible integrative roles for this LHRH-immunoreactive system are discussed. PMID- 2193042 TI - Intrinsic PEEP on static pressure-volume curves. AB - The static pressure volume (PV) curve of the total respiratory system is a well established method to assess pulmonary mechanics during respiratory failure. We have tested the impact of auto-PEEP on the PV curve determination in 16 COPD patients. An isovolumic pressure increment (IPI) was found at the beginning of the curve and a close correlation between IPI and auto-PEEP level (r = 0.962) p less than 0.001) was observed. The regression equation was not significantly different from the identity line. We conclude that the appearance of IPI in PV curves is largely determined by auto-PEEP and it is a good estimate of the existing auto PEEP level. PMID- 2193041 TI - Ventilatory management of ARDS: can it affect the outcome? AB - Animal studies have demonstrated that mechanical ventilation with high peak inspiratory pressure (PIP) results in acute lung injury characterised by hyaline membranes, granulocyte infiltration and increased pulmonary and systemic vascular permeability. This can result in progressive respiratory failure and death. In surfactant deficient lungs this occurs with tidal volumes (Vt) as low as 12 ml/kg, and PIP as low as 25 cm H2O, values which are frequently used clinically. The mechanisms resulting in this form of ventilator induced lung injury are not clear, but it appears to result from global or regional overdistension of the lung or terminal airways. It can be prevented or reduced in severity in some animal models by the use of PEEP. It is suggested that the use of high PIP in some patients may result in progressive deterioration of their ARDS, possibly contributing to mortality both from respiratory failure and other causes. It may be very important to limit PIP by reducing Vt even if this results in hypercapnia and a deterioration of oxygenation in the short term. PMID- 2193043 TI - High-frequency pulsation (HFP) in a patient with Guillain-Barre syndrome. AB - A patient with Guillain-Barre syndrome (GBS) developed a respiratory crisis despite recurrent treatment with plasma exchange. Thus mechanical ventilatory support became necessary. As an alternative to conventional ventilatory techniques high-frequency pulsation (HFP), a modified high-frequency jet ventilation technique was used. According to the observations HFP may be a valuable technique for the continuous adaptation to the patient's individual respiratory demands in GBS. PMID- 2193044 TI - Social reform versus education reform: university nursing education in Canada, 1919-1960. AB - Nurses' struggle to attain educational parity with other professional groups is closely aligned with the struggle of women for social equality within Canadian institutions. The attempts of nursing educators to shift their perspective from social reform to educational reform and to develop nursing scholarship has been restricted by the cultural views of women. Consequently, nurses' gains in attaining higher education have been realized by reforms in social and health care policies thought suitable for women. With advancement in university nursing education closely tied to social reform, nurses were not expected, nor did they expect, to pursue scholarly enquiry or develop research endeavours. This paper suggests that the feminist movement offers nurses a social and psychological basis from which to complete the educational reform of nursing. PMID- 2193045 TI - Study of the effects of education on the management of urine drainage systems by patients and carers. AB - A randomized controlled trial was undertaken to test the effects of an education programme, which included an information booklet and demonstration, on the management of urine drainage systems by patients and carers. A total of 45 patients, new and established users, were included. Data were collected at pretest, test and follow-up visits. The education programme was found to improve significantly the performance of handwashing after bag emptying and before and after bag changing, although this effect did not persist over time. The findings are discussed with a number of conclusions drawn and recommendations for nursing practice. PMID- 2193046 TI - Intravascular ultrasound imaging: in vitro validation and pathologic correlation. AB - Intravascular ultrasound imaging is a new method in which high resolution images of the arterial wall are obtained with use of a catheter placed within an artery. An in vitro Plexiglas well model was used to validate measurements of the luminal area, and an excellent correlation was obtained. One hundred thirty segments of fresh peripheral arteries underwent ultrasound imaging and the findings were compared with the corresponding histopathologic sections. Luminal areas determined with ultrasound imaging correlated well with those calculated from microscopic slides (r = 0.98). Three patterns were identified on the ultrasound images: 1) distinct interface between media and adventitia, 2) indistinct interface between media and adventitia but different echo density layers, and 3) diffuse homogeneous appearance. The types of patterns depended on the relative composition of the media and adventitia. Calcification of intimal plaque obscured underlying structures. Atherosclerotic plaque was readily visualized but could not always be differentiated from the underlying media. PMID- 2193047 TI - Effect of intermittent positive pressure ventilation on diastolic ventricular filling patterns in premature infants. AB - Eleven preterm newborn infants had a Doppler echocardiographic examination of their ventricular filling patterns during intermittent positive pressure ventilation. Peak velocity during early ventricular filling (VE) and during atrial systole (VA) and diastolic velocity-time integral of early (IE) and late (IA) ventricular filling caused by atrial contraction were measured. The ratios of VE/VA and IE/IA were also calculated. Diastolic peak velocities, as well as the diastolic velocity-time integral of early and late ventricular filling measured through the mitral valve were significantly higher during inspiration. The peak of the wave representing the velocity during atrial systole (A) was always higher than the peak of the wave representing the velocity of early ventricular filling (E). As a result, the ratio of these two variables (E/A) was always less than 1, showing no significant variation from inspiration to expiration. The flow patterns into the right ventricle were the opposite of those observed through the mitral valve. During inspiration, a significant decrease (p less than 0.001) in peak and time integral velocities of both the early ventricular filling and atrial systole waves was observed. Heart rate did not vary with respiration. It is concluded that during positive pressure ventilation, inspiration decreases right ventricular filling and enhances left ventricular filling. Opposite changes are recorded during expiration. Early and late phases of diastolic filling are equally affected. These changes are different from those observed during spontaneous breathing and should be taken into account in the assessment of diastolic ventricular function in preterm infants requiring assisted ventilation. PMID- 2193048 TI - Hemodynamic importance of systolic ventricular interaction, augmented right atrial contractility and atrioventricular synchrony in acute right ventricular dysfunction. AB - To delineate the determinants of right ventricular performance with acute right ventricular dysfunction, surgical electrical isolation of the right ventricular free wall was produced in 13 dogs. During atrioventricular (AV) pacing, hemodynamic and wall motion measurements were normal. When not paced, the right ventricular free wall became asystolic, resulting in a depressed and bifid right ventricular systolic pressure (33 +/- 5 to 18 +/- 4 mm Hg) and decreased left ventricular systolic pressure (100 +/- 18 to 80 +/- 18 mm Hg) and stroke volume (14 +/- 4 to 10.3 +/- 3.5 ml) (all p less than 0.05). Ultrasound demonstrated right ventricular free wall dyskinesia, increased right ventricular end-diastolic size (155 +/- 13% of control), but decreased left ventricular size (69 +/- 11% of control) (both p less than 0.05). Right atrial pressure increased (5.8 +/- 2.5 to 7.6 +/- 2.8 mm Hg, p less than 0.05) with an augmented A wave and blunted Y descent, indicating pandiastolic right ventricular dysfunction. The septum demonstrated reversed curvature in diastole and bulged paradoxically into the right ventricle during early systole, generating the initial peak of right ventricular pressure and reducing its volume. Later, posterior septal motion coincided with maximal left ventricular pressure and the second peak of the right ventricular waveform. Left ventricular pacing alone led to further decreases in right ventricular systolic pressure and size, left ventricular systolic pressure and stroke volume. The previously augmented A wave was replaced by a prominent V wave. Therefore, when contractility of its free wall is acutely depressed, right ventricular performance is dependent on left ventricular-septal contractile contributions transmitted by the septum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2193049 TI - Endothelial, platelet and leukocyte interactions in ischemic heart disease: insights into potential mechanisms and their clinical relevance. AB - Recent investigations of the complex interactions among vascular endothelium, platelets and leukocytes have relevance to the pathogenesis of atherosclerosis and ischemic heart disease. Perturbations in the hemodynamic equilibrium maintained by these cellular elements may lead to vasospasm, in vivo thrombosis and a reduction in blood flow. Recent advances in the understanding of these interactions in health and disease states are summarized. The effect of pharmacologic agents on these cell-cell interactions are discussed to provide the reader with a general understanding of the relevance of these interactions in cardiovascular disease. PMID- 2193050 TI - Optimal utilization of thrombolytic therapy for acute myocardial infarction: concepts and controversies. AB - Timely administration of thrombolytic therapy decreases myocardial infarct size, lessens the incidence of congestive heart failure and improves survival. However, available data suggest that only 10% of patients with acute infarction in the United States receive thrombolytic drugs. Given the benefits of thrombolytic therapy, all patients with myocardial infarction would likely be treated were it not for associated risks. Several groups exist in which the risk/benefit ratio of thrombolytic therapy continues to be controversial, including those with inferior infarction, absence of ST segment elevation or presentation greater than 6 h from symptom onset, elderly patients and those with hypertension. Three recent thrombolytic trials reported a reduction in mortality that was entirely independent of infarct location. Pooled data from trials involving 12,000 patients with inferior infarction have demonstrated a reduction in mortality rate (6.8% versus 8.7%, p less than 0.0001). Furthermore, improvement in regional and global left ventricular function occurred after reperfusion therapy of inferior infarction. Pooled data indicate that patients treated between 6 and 24 h after symptom onset have a lower mortality rate than do those who receive placebo (11.1% versus 13.1%, p less than 0.001). Improved survival occurs after thrombolytic therapy in patients with ST segment elevation or left bundle branch block, but not in those with isolated ST depression or a normal electrocardiogram. Age should not be considered an absolute contraindication because the lifesaving potential of thrombolytic therapy in the elderly may be two to three times that of the overall group of patients with myocardial infarction. Finally, recent studies demonstrated that patients who present with hypotension or hypertension or who have undergone cardiopulmonary resuscitation may also benefit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2193051 TI - Rate-dependent bundle branch block: occurrence, causes and clinical correlations. PMID- 2193052 TI - Icosanoid synthesis as a functional measurement of essential fatty acid requirement. PMID- 2193053 TI - Erwin H. Ackerknecht 1906-1988. Some memories. PMID- 2193054 TI - The use of the passions in psychological healing. PMID- 2193055 TI - The ancient physician: craftsman or scientist? PMID- 2193056 TI - Clinical research and basic science: the development of the concept of end-organ resistance to a hormone. PMID- 2193057 TI - Cryptosporidium parvum merozoites share neutralization-sensitive epitopes with sporozoites. AB - Sporozoites and merozoites are stages in the life cycle of Cryptosporidium parvum that can cyclically infect intestinal cells, causing persistent infection and severe diarrhea in immunodeficient patients. Infection by sporozoites can be neutralized by surface-reactive mAb. We show that merozoite infectivity can also be neutralized by surface-reactive mAb. To do this, viable C. parvum merozoites were isolated by differential and isopycnic. centrifugation, and distinguished from sporozoites by transmission electron microscopy. Differential reactivity with a panel of seven mAb was used to determine the amount of sporozoite contamination in isolated merozoite preparations. The isolated merozoites were distinguished from sporozoites (p less than 0.0001) by four sporozoite-specific mAb (16.332, 16.502, 17.25, and 18.357) in an indirect immunofluorescence assay. Three mAb (16.29, 17.41, and 18.44) consistently reacted with both merozoites and sporozoites. Isolated merozoites were infectious for neonatal mice when administered by intraintestinal injection. Infectivity for mice was significantly neutralized (p less than 0.05) when 1 to 2 x 10(5) merozoites were incubated with sporozoite-neutralizing mAb 17.41 or 18.44, before inoculation. Merozoites incubated with an isotype control mAb remained infectious for neonatal mice. We conclude that C. parvum merozoites share neutralization-sensitive epitopes with sporozoites. PMID- 2193058 TI - Anti-actin antibodies: a new test for an old problem. AB - Smooth muscle antibodies with anti-actin specificity are commonly regarded as markers of autoimmune liver disease. However, there are interpretational problems because different techniques have been used for their identification and therefore the results are difficult to compare. The present paper reports the results of a new method for the identification of anti-actin antibodies (indirect immunofluorescence on cryostat sections of liver from rats chronically injected with phalloidin). The results have been compared with those obtained by four other techniques: demonstration by immunofluorescence of kidney peritubular reactivity (SMAT), of anti-microfilament antibodies (on HEp-2 cells and vinblastine-treated peripheral blood mononuclear cells) and counterimmunoelectrophoresis with purified muscle actin as antigen. The new method proved to be the most sensitive and specific. Furthermore, its reproducibility was found to be high, the interpretation easy and the cost low. The clinical significance of anti-actin antibodies in patients with chronic liver disease is also discussed. PMID- 2193059 TI - Imaging infections with antibodies. A quantitative autoradiographic analysis. AB - Radiolabeled IgG has recently been demonstrated to effectively image infections. A potential but unproven mechanism for this localization is the specific binding of IgG to Fc receptors on the surface of inflammatory cells in infections. In an animal model of soft tissue infection, quantitative autoradiography was used to measure 125I-labeled IgG and albumin in tissues with a spatial resolution sufficient to associate these proteins with cellular morphology. Gamma camera images at 24 h localized the infection with target-to-background ratios of 2.2 +/ 0.5 for IgG and 2.3 +/- 1.0 for albumin (mean +/- SD). Using quantitative autoradiography at 1 h post-injection, significantly higher concentrations were found in infected thighs of 2-4% of initial plasma concentrations (CPo) as compared to 0.2-0.3% of CPo in noninfected thighs (P less than 0.05); at 24 h post-injection, higher concentrations (7-8% of CPo) were found in infected thighs. Radiolabeled proteins were not inflammatory cell associated and were localized primarily within the edematous interstitial spaces of the infection. PMID- 2193060 TI - False-positive signals in enzyme immunoassay (EIA) interactions between rodent IgG subclasses. AB - Interactions between mouse and rat monoclonal antibodies (MAbs) in EIA have been detected using panels of mouse and rat MAbs of various isotypes. Mouse and rat antibodies of the IgG2a subclass were found to bind to each other most strongly. Immobilised IgG1 antibodies of the two species showed much less interaction. Rat IgG2b and IgG2c were intermediate in binding activity. We were unable to study examples of mouse IgG2b and IgG3 MAbs. By making use of the kappa light chain allotype in the rat we were also able to show intraspecies interactions of rat MAbs with the IgG in rat serum. The molecular basis of these interactions has not been resolved but may involve the extended hinge region and flexible Fab arms of the IgG2a subclass of Ig permitting strong inter domain bonding between the constant region domains of adjacent molecules of this isotype. PMID- 2193061 TI - Phagocytosis of Mycobacterium leprae by cardiac muscle cells--a preliminary report. AB - Fetal cardiac muscle cells were shown to ingest M. leprae easily within 20 minutes of exposure in vitro. This phagocytosis is considered nonspecific and facilitated by the lipid coat of the mycobacteria. The presence of M. leprae free in the cytoplasm of the muscle cells did not seriously affect the morphology or rhythmic contractions of the cells. The significance of the presence of M. leprae in somatic cells needs further study. PMID- 2193062 TI - Comparative evaluation of enzyme immunoassays based on synthetic glycoconjugates and phenolic glycolipid-I for immunodiagnosis of leprosy. AB - Enzyme immunoassays (EIAs) based on synthetic glycoconjugates containing the terminal monosaccharide (M-BGG) or disaccharide (ND-BSA) residue of the trisaccharide component of phenolic glycolipid-I (PGL-I), for immunodiagnosis of leprosy are described. The results of the assays were compared with that of the EIA using PGL-I. All the three assays were highly specific for leprosy. The per cent positivity of active lepromatous leprosy (LL) patients with M-BGG was 78.05 in comparison to 85.36 with ND-BSA and 82.11 with PGL-I. Similarly, the positivity of tuberculoid (TT) leprosy patients in M-BGG assay was lower than that in EIAs using ND-BSA or PGL-I. However, the difference in the positivity of individual category of leprosy patients in the three EIAs was not statistically significant. The correlation between absorbance values of leprosy sera in EIAs based on M-BGG and PGL-I, as well as that in assays using ND-BSA and PGL-I was statistically significant. PMID- 2193063 TI - An in vitro culture method for screening new drugs against Mycobacterium leprae. AB - An in vitro culture system has been devised for the maintenance and growth of M. leprae in a cell-free medium. Cells from four-week old cultures could be transferred to fresh medium and normal growth was observed in subcultures. Using this system, the M.I.Cs of dapsone and rifampicin were determined. Dapsone at 25 ng/ml and rifampicin at 300 ng/ml completely inhibited the growth of host-grown as well as in vitro-adapted M. leprae. It was further shown that the effects of both the drugs were bactericidal; this observation was subsequently confirmed using mouse foot-pad technique. PMID- 2193064 TI - Effect of brodimoprim on Mycobacterium leprae in vitro and in mouse foot-pads. AB - The new in vitro screening system reported earlier was adopted to determine anti M. leprae activity of a dihydrofolate reductase inhibitor, brodimoprim, and the results were compared with those obtained using mouse foot-pad technique. Even though the MIC of brodimoprim against M. leprae was very high compared to other commonly used anti-leprosy drugs, in combination with dapsone it showed a remarkable synergistic activity in inhibiting the growth of M. leprae at concentrations much lower than the MICs of each of the drugs used singly. Similar effects were also demonstrated in mouse foot-pad experiments. PMID- 2193065 TI - [Inhibition of enteropathogens by Clostridium butyricum MIYAIRI 588]. AB - The inhibitory effect of Clostridium butyricum MIYAIRI 588 against various enteropathogens was investigated in mixed cultures. It was observed that C. butyricum M588 inhibited the growth of Vibrio cholerae O1, V. cholerae non-O1, Aeromonas hydrophila, and Shigella flexneri. Considering that the interaction between C. butyricum and Shigella is especially important because of their proliferation site in the lower intestine, further examinations were carried out on Shigella in particular. Results were as follows: 1) In BHI broth culture of Shigella, the pH of culture fluid went down to 5.2, but the growth of Shigella was not inhibited. 2) In the mixed culture of Shigella and C. butyricum, the growth of Shigella was inhibited, nevertheless the pH of the culture fluid was 5.6. 3) In the mixed culture with phosphate buffered BHI maintaining the pH higher than 6.0, the growth of Shigella was inhibited. 4) In case of pure culture of C. butyricum in BHI broth, the pH of culture fluid indicated 5.5, and Shigella failed to grow in the cell free culture supernatant. 5) The growth of Shigella was not inhibited in the culture supernatant when the pH was adjusted at 7.2. These results suggested that the inhibition of Shigella in the mixed culture with C. butyricum was not due to a single factor such as pH or fatty acid etc. but due to multifactors including live cells of C. butyricum. PMID- 2193066 TI - [Comparison between culture method and direct immunofluorescence test for detection of Chlamydia trachomatis and follow-up survey of antigen positive patients]. AB - C. trachomatis isolation by culture method using McCoy cells and direct immunofluorescence test (DFA) were carried out on specimens collected from patients with suspected chlamydial infections and the results were compared. Follow-up survey was also made on C. trachomatis positive patients. The results are summarized as follows: 1) One thousand and eighty-six specimens were examined. Positive-coincidence ratio obtained from both methods was 80% and negative-coincidence ratio was 92%. The antigen detection by the DFA exceeded a little bit in positive ratio than that by the culture method. 2) C. trachomatis was positively detected in 31 of 94 men (33%) and 5 of 27 (17%) women during periods from 7 days to 2.5 years in follow-up examinations. PMID- 2193067 TI - [Actual conditions of bacterial infection associated with hematopoietic disorders -changes in 10 years. The Hanshin Study Group of Hematopoietic Disorders and Infections]. AB - This study showed several accumulated data through ten years from our experience in hematopoietic disorders and associated infections, which has been analyzed by the Hanshin Study Group of Hematopoietic Disorders and Infections. Since 1979 to 1988, our group had evaluated the sorts of causative organisms and the efficacy of various antibiotics therapy in 2119 cases of infectious diseases associated with hematopoietic disorders. On behalf of evaluating the changes of disease profile for ten years, we divided the accumulated data into three phases; former phase the first three years, middle phase the second three years and late phase the last four years. There was no significant difference in the frequency of various hematopoietic disorders among the three phases. Each leukemia patients occupied 77% of all cases. Sepsis suspected is the most frequent infectious disease accounting for 68.8%. The other infectious diseases were 8.4% of the sepsis, 14.8% of the respiratory infections and 3.1% of the urinary tract infections. Comparing the frequency of infections among the three phases, the respiratory and urinary tract infections inclined to decrease. Of the 532 strains isolated from 2119 cases and identified as causative organisms, gram-negative bacilli occupied 62.8% and gram-positive bacteria 36.5%. In comparing the percentage of gram-negative bacilli among the three phases, it showed a decreasing tendency in order former phase 63.6%, middle phase 76.4% and late phase 43.8%. Pseudomonas, however, had been isolated at almost constant ratio through ten years. On the other hand, the ratio of gram-positive bacteria isolated were 34.5% in former phase, 23.6% in middle phase and 56.3% in late phase, showing increasing a tendency through the period. Twenty-three kinds of antibiotics were administered by intravenous drip infusion. The efficacy rate was 43.9% to 67.2%. In particular, effectiveness of antibiotic therapy often depends on the change of peripheral neutrophil counts from the onset and during the therapy. The efficacy rate, however, was 36% even neutrophil counts have not shown the tendency of increase from less than 100/microliters. PMID- 2193068 TI - Antigenicity of group B Streptococcus strain "M9" and its prevalence in Japan. AB - Serological typing of group B streptococci is important for the epidemiological study of group B streptococcal infections. These days, non typable (NT) strains by conventional serotypes were on an increase. In 1984, strain "M9" was isolated from a pregnant woman in Meijo Hospital, Nagoya City; herein the antigenicity and prevalence of strains typed as "M9" were investigated and discussed. The results obtained were as follows: 1) It was confirmed that strain "M9" had a new polysaccharide antigen, different from conventional types, Ia, Ib, II, III, IV and V, type candidate NT6 and type candidate 7271, as found by precipitation and precipitation absorption reaction. This procedure, moreover, was useful for differentiation type candidate NT6 and 7271 from "M9" because of their provisionality. 2) Group B streptococci typed as "M9" were isolated not only from carriers but from patients who were newborn babies and suffered from sepsis. 3) Strain "M9" was not necessarily located in Nagoya City but in Chiba and in Kyoto, this type was isolated from clinical materials already in 1979. 4) It was observed that polysaccharide "M9" liked to combine with protein "R" and without other proteins, as our collection extends. PMID- 2193069 TI - [Levels of CA130 in maternal sera and amniotic fluid at various gestational ages]. AB - We examined the CA130 concentration in the amniotic fluid, maternal sera, amnion, chorion, decidua and placenta. CA130 in the maternal sera showed an initial increase during early pregnancy, remained low from the 15th weeks of pregnancy until delivery, and then increased after term delivery (249u/ml, mean, n = 27) or mid-trimester abortions (844u/ml, n = 22). The CA130, concentration in the amniotic fluid was high in the mid-trimester and remarkably low at term. Among the tissues examined, amnion and decidua contained a relatively high concentration of CA130. Immunohistochemical examination also demonstrated abundant CA130 in the cytosol of amnion and decidua tissues. The pattern of changes in CA130 in amniotic fluid was similar to that in the amnion and decidua tissue. The results suggest that the amnion cells are the source of CA130 in the amniotic fluid and that the high concentration of CA130 in maternal serum after delivery originates in decidua tissue affected by the separation of the placenta. PMID- 2193070 TI - [Prenatal diagnosis of infantile polycystic kidney disease; a case report]. PMID- 2193071 TI - Is analgesia required for transvaginal single-follicle aspiration in in vitro fertilization? A double-blind study. AB - High oocyte retrieval rates using transvaginal follicular aspiration for single follicles and improved laboratory techniques have engendered renewed interest in natural-cycle in vitro fertilization (IVF). To assess analgesia requirements during single-follicle aspiration, a double-blind study was set up in 30 patients comparing intraprocedure intravenous fentanyl with normal saline as a placebo. Analysis of pain perception using visual analogue scoring showed a similar pain tolerance in both groups for the procedures of vaginal ultrasound scanning, needle insertion, and follicular aspiration. A correlation between each patient's tolerance of common pain-producing experiences with that for the procedure was not well defined (r = 0.5). We conclude that one of the benefits of natural-cycle IVF using transvaginal single-follicle aspiration is that it can be performed without analgesia. PMID- 2193072 TI - Physicochemical properties of follicular fluid and their relation to in vitro fertilization (IVF) outcome. AB - Despite the limited data that are available concerning FF physicochemical properties, the following conclusions can be drawn. (1) FF temperature is lower than ovarian stroma and body temperatures. The physiological significance of this gradient is unknown. (2) Follicular size increases exponentially prior to ovulation. The relationship between FF volume and successful IVF outcome is well established. (3) A highly significant association exists between fertilization (but not embryo cleavage) and FF spectrophotometric absorbance at delta optic density of 455 nm. (4) FF behaves as a non-Newtonian fluid--its viscosity changes at different shear rates. Neither FF viscosity nor its refractive index was found to correlate with the presence of oocytes, their maturation grade, or their fertilizing capacity. (5) FF osmolarity is similar to that of the plasma. There is no information linking variations in FF osmolarity to IVF outcome. (6) FF pH is acidic, probably due to acid mucopolysaccharides. It appears that the intact follicle is capable of buffering any carbon dioxide which diffuses through its wall at the time of intraperitoneal insufflation. The transvaginal aspiration technique eliminates any possible effect of exogenous gas on FF pH. (7) Regarding the intact follicle, it was shown that (a) there is a small potential difference across the follicle wall, and (b) intrafollicular pressure remains steady prior to ovulation. This information may shed some light on mechanisms underlying FF formation and ovulation. No experiments relating these properties to IVF outcome have been performed. PMID- 2193073 TI - Basic principles and clinical applications of the transvaginal Doppler duplex system in reproductive medicine. PMID- 2193074 TI - Pneumatosis cystoides intestinalis (PCI). AB - Pneumatosis cystoides intestinalis (PCI) is a rare disease usually occurring in association with a large variety of gastrointestinal (GI) and non GI conditions in the majority of cases, although idiopathic PCI is also known to occur. There are two theories regarding the development of these intramural gas cysts--the mechanical and bacterial theories. PCI usually runs a benign course, although fulminant PCI can be present both in infants and adults. The importance of this condition for the surgeon lies in its early recognition, in order to prevent unnecessary surgical intervention, especially when pneumoperitoneum without clinical evidence of peritonitis is encountered. Oxygen therapy has been shown to lead to regression of PCI, although recurrences have been reported. Elemental diets and antimicrobial agents have provided symptomatic relief in a few reported cases. The association of PCI with a wide variety of conditions leads us to conclude that PCI may not be a disease in itself, but a sequel to these varied conditions. PMID- 2193075 TI - Topical treatment with 5-aminosalicylic in distal ulcerative colitis by using a new suppository preparation. A double-blind placebo controlled trial. AB - Sixty-two patients with ulcerative colitis localised to the distal sigmoid colon and rectum (less than 20 cm) entered the trial. Thirty-two were treated with 5 ASA 500 mg suppositories (Asacol) 3 times a day for 1 month while 30 received a placebo given in the same regime. Clinical, sigmoidoscopic and histological assessment was carried out before, after 15 days and after 1 month of treatment. At the end of the study 5-ASA suppositories showed significantly better results in all the parameters recorded than placebo (p less than 0.01). There were no unwanted effects related to the use of suppositories. This treatment should therefore be offered as a first choice for patients with distal rectosigmoiditis. PMID- 2193077 TI - Where do we go from here? PMID- 2193076 TI - Endorectal sonography in the management of rectal villous tumours. AB - Thirty-seven patients with rectal villous tumours were investigated by endorectal sonography to assess the integrity of the rectal muscularis propria at the tumour level. In four cases assessment of invasion was impossible. In 24 patients, endosonography revealed an ultrasonically superficial lesion not infiltrating the muscular layer. This was confirmed either, in the case of laser treatment, by the absence of malignant recurrence during the follow-up period or by histological examination after surgical resection. In nine patients, endosonography showed infiltration of the muscular layer. This was histologically confirmed in five operated patients. In the remaining four, laser destruction was performed: in two, a rectal adenocarcinoma was present 3 and 6 months later, respectively. These findings show that endosonography has a place in the management of rectal villous tumours, demonstrating invasive cancer in cases where other forms of assessment were wrongly reassuring. PMID- 2193078 TI - Cytoplasmic components of natural killer cells limit the growth of Cryptococcus neoformans. AB - Murine natural killer (NK) cell-mediated inhibition of growth of a yeast-like target cell, Cryptococcus neoformans, was completely abrogated by blocking the effector cell secretory process with monensin. Therefore, further studies were performed to determine the ability of various cytoplasmic fractions of NK cells to mediate inhibition of cryptococcal growth. Percoll-fractionated homogenates of rat LGL tumor cells demonstrated that the granule-containing fractions plus three additional sets of less dense cytoplasmic fractions displayed anti-cryptococcal activity; whereas only the cytoplasmic granule-containing fractions had cytotoxic activity against YAC-1 tumor cell and sheep erythrocyte targets. Maximal cryptococcal growth inhibition induced by LGL granules occurred after a 1 h incubation, required the presence of Ca2+ (1.0 mM) or Mg2+ (0.5 mM or 5.0 mM), and was completely abrogated in the presence of rabbit anti-LGL granule IgG. Cytolysin, the granule component which mediates tumor cell and sheep erythrocyte lysis, effectively limited the growth of cryptococci. Since Percoll gradient fractionation of the LGL homogenates demonstrated three separate peaks of anti cryptococcal activity other than the granule peak, it is possible that the cytolysin-containing granules are not the only subcellular component of NK cells playing a role in inhibition of C. neoformans growth. PMID- 2193079 TI - Mechanisms of neutrophil-mediated killing of endothelial cells. PMID- 2193080 TI - [Procedures in critical ischemia of the legs in non-emergency situations]. AB - Our experience with 91 operated cases in 84 patients (47 men, 37 women) relates essentially to arterial diseases resulting from overloading and diabetic arteriopathy. Diagnosis of critical ischemia is easy in clinical conditions, but it is advisable to rely on universally recognized hemodynamic standards to define this condition. Ankle pressure should be less than 400 mmHg and the Doppler trace flat or barely perceptible. Patients in our series had a mean ankle pressure of 32.4 mmHg. Local examination can determine the extent of gangrene, whereas general examination detects numerous, often associated defects diabetes, coronary artery disease, rhythm disorders, arterial hypertension, etc. As far as possible, these defects are to be corrected before surgery. X-ray examination (M. Kasbarian) is frequently done in conjunction with conventional aorto arteriography and digital angiography. The later technique allows arteries to be visualized which are not seen with the conventional technique. The x-ray examination will indicate whether revascularization is feasible, although it cannot show whether it will be efficient. In our series, opacification of the plantar arches was predictive neither of success nor failure. But do tests exist which can predict the success of a revascularization attempt? It would be necessary to be able to estimate ankle pressure after the operation, and several methods have tried to do this. TcPO2 would seem to be a good examination. The possibilities of nuclear magnetic resonance are being studied, and the results thus far are promising. Preoperative explorations are carried out in a different situation. Arteriography performed in the operating room is a simple act which can reveal a usable downstream bed not indicated in preoperative X-rays, although it provides no hemodynamic data. Measurement of peripheral resistances would appear to be a very good predictive examination. Flow measurements by infusion or electronic flowmeter also seem to be predictive for bypass results. Unfortunately, these measurements are at present not widely performed and the critical threshold is assessed differently. Given the difficulty of correctly estimating the value of these numerous methods, many surgeons, ourselves included, have chosen to revascularize patients whenever the upstream bed as evaluated by X-ray indicates the presence of at least one viable artery. PMID- 2193081 TI - [The current role of lymphoscintigraphy in the study of lymphedema of the limbs]. AB - After a brief review of the classical methodology and results of lymphoscintigraphy, the technique is considered in terms of an original kinetic study approach. Immediately after distal subcutaneous injection of a technetium colloid (rhenium sulfocolloid), 40 1-min serial images of the limbs are recorded followed 4 h after injection by recording of static images. The main abnormalities detected by scintigraphy concern the lymphatic vessels, nodes and interstitium. They reveal the presence of lymphedema and provide information about its mechanism, indicating, particularly in the case of primary lymphedema, whether there is predominant hyperplasia or hypoplasia in vessels or nodes. Synoptic study of the initial dynamic recording based on simple examination of serial images is difficult. Complementary data provided by activity curves determined from manually selected regions of interest (ROI'S) are of limited value since the ROI'S correspond to superimposed spatial structures. Two data processing techniques--the condensed image (CI) and factorial analysis (FA)--were therefore applied to dynamic scintigraphic recordings in order to study lymphatic progress of the radiotracer in the legs. A complete dynamic series is described in two IC, one for each leg. The CI, obtained by mounting the 40 serial images in vertical strips 1 pixel in width, describes the spatial distribution of radioactivity along the leg during recording. Factorial analysis provides automatic extraction of pure kinetic components or factors from the dynamic series despite their spatial superposition. The factors are described by factorial curves and factorial images representing the spatial identity of the factor. Three-factor FA was applied successively to each leg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2193082 TI - [Surgical treatment of lymphedema]. AB - In our experience, indications for surgical management of lymphedema do not amount to more than 10% of cases. Surgery is significantly complemented by expert pre and postoperative physiotherapy. Excisional procedures are presently seldom carried out, although they may be helpful when carried out as simple "orange slice"-type resection, or as the Thompson operation. Liposuction is an attractive alternative, but its effectiveness needs be confirmed yet. Actually, the most effective types of surgical treatment are microsurgical lymphovenous or lymphoveno-lymphatic bypass. Secondary lymphedema of the lower extremities (more rarely of the upper limbs) are primary indications. The Campisi-Casaccia team from Genoa has acquired interesting experience with congenital lymphedema. Results relating to surgical treatment of lymphedema can be assessed only after a follow-up of 3-5 years. About one third of cases, on average, do very well and another third do well. Elastic support of the leg must practically always be maintained. PMID- 2193083 TI - [The role of oscillometric, oscillographic and rheographic methods in assessing arteriopathy of the legs]. AB - The oscillometric method records arterial wall oscillations during pulse wave and index pressure. Sensitivity increases with reactive hyperemia but many artefacts influence his technic. Electronic oscillography is more sensitive but has similar limits and a very high cost. This two methods detect easily arterial occlusive lesions but give only few information about the severity of arterial disease. On the opposite, Irrigraphy (impedance plethysmography) is a functional non invasive technic. Perfected by R. Sarrazin, J. F. Picard and A. Franco, it consists in recording the signal generated by electrical impedances variations related to pulse volume and heart rate. The pulse volume curve is recorded at six different positions of the leg. This method permits the evaluation of collateral vessels. Automatization of this non invasive technic increased reliability, and saves time examination. PMID- 2193084 TI - [Unusual pathology of the popliteal space. Popliteal artery entrapment]. AB - After reviewing the main anatomical anomalies responsible for the popliteal artery entrapment syndrome, the author emphasizes the need for early diagnosis prior to onset of complications. Whenever confronted with hamstring pain due to sports-related physical stress in a youngster, loss of posterior tibial and pedal pulse should be checked for during static contraction, and then during forced passive stretching of the gastrocnemius muscle; modifications in arterial Doppler tracings during these maneuvers will confirm the diagnosis. Should this fail to occur at this early stage, severe complications will develop in time, manifested primarily by thrombosis of the popliteal artery; ectasia of this artery in itself carrying a risk of further peripheral embolism, thrombosis and rupture. PMID- 2193085 TI - [Cystic adventitial disease of the popliteal artery]. AB - This strange lesion has been described as colloid degeneration, adventitial cyst, adventitial cystic disease, cystic degeneration of the popliteal artery. The disease was also observed in other localizations and the first case, which was described in 1946 by Atkins and Key (I) concerned an iliac artery. Bizard (2) in 1978 reported a case of the common femoral artery. Ejrup and Hiertonn (4) described the first popliteal localization in 1954. Bergan in 1970 reported 40 cases and collected 115 operated cases in Rutherford's Vascular Surgery (5). Usually a young patient complaints from a recent severe intermittent claudication. At surgery a cystic lesion is found into the adventitia of the popliteal artery, containing gelatinous material which may be easily evacuated without opening the lumen of the artery. This lesion is totally different from atheroma and also from medial cystic necrosis as described by Erdheim. PMID- 2193086 TI - [Popliteal vein entrapment, popliteal cyst, desmoid tumor and fabella syndrome]. AB - The popliteal fossa is a relatively small, muscle-bound strategic anatomical area where is found, on the posterior aspect of the knee, a vasculonervous pedicle and where both vascular and pseudovascular disease may develop, the latter originating from wall-constituting parts. Among non-typical popliteal diseases, the authors have singled out four rare syndromes. The popliteal vein may be trapped due to fibrous strangulation or, more often, to compression by the hypertrophied gastrocnemius muscle. This requires proper diagnosis and surgical management prior to thrombosis onset. Synovial cysts raise no diagnostic problems, unless they mimic an episode of phlebitis; echotomography has now become essential for diagnosis. Desmoid tumors for which predominant extra abdominal occurrence sites are the popliteal fossa, the leg and thigh, are difficult to excise completely, especially at the popliteal level, and are a major technical challenge because of the inclusion of the vasculonervous pedicle. Lastly, in sports pathology, one must be able to recognize the painful fabella syndrome (osteochondritis of sesamoid fibrocartilage in lateral head of gastrocnemius), so as not to mistakenly implicate vascular disease. New developments in imaging (namely, real time CT-echography) are of major help to clinicists, who should, nonetheless, remain chiefly responsible for detecting these diseases. PMID- 2193087 TI - [Aneurysm of the popliteal vein]. AB - Aneurysms of the popliteal vein are rare. They often seem to be favored by parietal dysplasia, but this is not a consistent finding. From a clinical viewpoint, the lesion is often asymptomatic. It may be detected fortuitously through the occurrence of a popliteal mass. In more severe cases, pulmonary emboli originating at the aneurysmal site will occur. As a rule, diagnosis is based on results from investigations such as phlebography and, more recently, echography which is bound to have a more important role in this field. Management must take the patient's history and background into account, depending upon which treatment will consist of either mere surveillance of asymptomatic patients, or resection possibly followed by restoration of venous circulation--placement of a caval block being restricted to very particular cases. PMID- 2193088 TI - [Physiopathology of the cerebral arterial circulation. Application to cerebro arterial surgery]. AB - Autoregulation of cerebral arterial circulation corresponds to a hemodynamic reserve enabling normal cerebral blood flow to be assured when arterial blood pressure drops. However, the capacity of this autoregulatory system is exceeded when pressure drops below 60 +/- 10 mmHg, at which time metabolic disturbances appear followed by the arrest of electric activity and the death or neurons. These ischemic phenomena involve more or less extended regions: cerebral or choroidal arterioles or arteries, or even those of the entire brain. They can occur in series as, for example, the embolism of a cerebral arteriole or artery in a brain already globally hypoperfused downstream from a carotid occlusion or narrow stenosis. The association of these phenomena accounts for the different clinicopathologic cerebrovascular accidents. These disturbances of cerebral blood flow can be explored clinically by isotopic techniques. A cerebral perfusion blood pressure drop can be suspected, when nonhemispheric symptoms appear, on the basis of ophthalmodynamometry, oculoplethysmography or changes in intracranial arterial velocity (transcranial Doppler examination) during the Diamox (Acetazolamide) test. After release of carotid clamping or correction of a "hemodynamically significant" stenosis, increased cerebral blood flow can be observed, with sometimes a "cerebral hyperperfusion" syndrome similar to that of hypertensive events which exceed the capacities of cerebral arterial autoregulation. PMID- 2193089 TI - An open letter to the Georgia Medical Care Foundation and the Department of Medical Assistance. PMID- 2193090 TI - Congress listens to Georgia physicians. PMID- 2193091 TI - Ciguatera. PMID- 2193092 TI - Diagnosis of renovascular hypertension: the captopril stimulation test. PMID- 2193093 TI - The Journal prepares for its second century. PMID- 2193094 TI - Interleukin 6 induces human immunodeficiency virus expression in infected monocytic cells alone and in synergy with tumor necrosis factor alpha by transcriptional and post-transcriptional mechanisms. AB - The immunoregulatory cytokine interleukin 6 (IL-6) directly upregulates production of human immunodeficiency virus (HIV) in acutely as well as in chronically infected cells of monocytic lineage. In addition, IL-6 synergizes with tumor necrosis factor alpha (TNF-alpha) in the induction of latent HIV expression. Unlike TNF-alpha, upregulation of viral expression induced by IL-6 alone does not occur at the transcriptional level and it is not associated with accumulation of HIV RNA. However, when IL-6 and TNF-alpha synergistically stimulate HIV production, accumulation of HIV RNA and increased transcription are observed, indicating that IL-6 affects HIV expression at multiple (transcriptional and post-transcriptional) levels. PMID- 2193095 TI - Identification and characterization of pro-T lymphocytes and lineage-uncommitted lymphocyte precursors from mice with three novel surface markers. AB - The study of prethymic stages of T cell development has been limited because specific markers for mouse pro-T lymphocytes were not available. We developed a panel of rat monoclonal antibodies (mAbs) that bind to our pro-T lymphocyte clones obtained from bone marrow of young adult mice and the thymus of 14-d-old embryos. The mAbs, called Joro 30-8, Joro 37-5, and Joro 75, were found to bind to all pro-T clones tested but not to cell lines representing later stages of T cell development, B lymphocyte, or myeloid lineages. We determined the frequency and tissue distribution in normal and immunodeficient mouse strains as well as the ontogeny in liver and thymus of cells positive for these mAbs. The results were consistent with the pattern of reactivity observed with cell lines. We isolated Joro 30-8+, Joro 37-5+, and Joro 75+ bone marrow cells by cell sorter and found that: (a) phenotypically, they are Thy-1+, CD4-, CD8-, CD3-, B-220-, IgM-, F4/80-, and PgP-1+; (b) they grew in response to the combination of interleukin 3 (IL-3) + IL-4 or IL-3 + IL-4 + IL-6; and (c) Joro 37-5+ and Joro 75+ marrow cells gave rise to mature T lymphocytes but not to B lymphocytes, while Joro 30-8+ marrow cells generated both T and B lymphocytes after 8-12 wk of transfer into severe combined immunodeficient (Scid) mice. In normal mice subjected to 600 rad of irradiation to induce a wave of thymus recolonization, we found by flow fluorocytometry analysis that Joro+ cells entered the thymus 2 d after irradiation, expanded during the next 4 d, and underwent further differentiation, and from day 8 up to day 21, post-irradiation Joro+ cells were no longer detectable in the thymuses. Immunohistochemical analysis of normal thymus shows the presence of very few Joro 30-8+, Joro 37-5+, and Joro 75+ lymphoid cells in the subcapsular area and outer cortex but not in the medulla. The kinetic analysis of tissue sections from thymuses at various days post irradiation suggests that Joro+ cells enter the thymus via blood vessels through the subcapsular and outer cortex areas; subsequently, these cells seem to migrate to the inner cortex without reaching the medulla, and give rise to Joro- thymocytes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2193096 TI - Phagocytosis of tumor cells by human monocytes cultured in recombinant macrophage colony-stimulating factor. AB - Macrophages and cultured human monocytes can mediate efficient antibody-dependent cytotoxicity (ADCC) against human tumor cells using monoclonal antibodies (mAbs). The mechanism of this killing is usually assumed to involve secreted factors (reactive oxygen intermediates, tumor necrosis factor, or other cytotoxic factors) leading to target cell lysis. In this study, we present evidence that phagocytosis of intact target cells is the principal mechanism of antitumor cytotoxicity in our in vitro model of ADCC by cultured monocytes. Human monocytes cultured in recombinant human macrophage colony-stimulating factor ingested up to 100% of fluorochrome-labeled melanoma and neuroblastoma target cells, in the presence of an appropriate antitumor mAb. Electron microscopy demonstrated phagocytosis of intact tumor cells by cultured monocytes during ADCC. All of the radionuclide in radiolabeled target cells was taken up by monocytes during phagocytosis. By preventing the release of radioisotope tracers, phagocytosis thus prevents the detection of this very efficient form of cytotoxicity by most conventional assays. PMID- 2193098 TI - Identification of cell surface receptors for the Act-2 cytokine. AB - We have identified cell surface receptors for Act-2, a secreted protein expressed upon activation of T cells, B cells, and monocytes. Although 125I-Act-2 showed little, if any, specific binding to resting peripheral blood lymphocytes (PBL) receptors were readily detected on PHA/PMA-activated PBL and a variety of cell lines including MT-2, HL60, DMSO differentiated HL60, HeLa, and K562 cells. The equilibrium dissociation constant (Kd) is 3-12 nM for MT-2, K562, and PBL activated with PHA/PMA for 40-80 h. We have also identified a rabbit polyclonal antiserum that can block Act-2 binding to its receptors. The ability to detect specific Act-2 receptors and the development of a blocking antiserum should prove valuable in efforts to molecularly clone the Act-2 receptor and to dissect the biological actions of Act-2. PMID- 2193097 TI - Lipopolysaccharide is a potent monocyte/macrophage-specific stimulator of human immunodeficiency virus type 1 expression. AB - Lipopolysaccharide (LPS) potently stimulates human immunodeficiency virus type 1 long terminal repeat (HIV-1-LTR) CAT constructs transfected into monocyte/macrophage-like cell lines but not a T cell line. This effect appears to be mediated through the induction of nuclear factor kappa B (NF-kappa B). Electrophoretic mobility shift assays demonstrate that LPS induces a DNA binding activity indistinguishable from NF-kappa B in U937 and THP-1 cells. LPS is also shown to dramatically increase HIV-1 production from a chronically infected monocyte/macrophage-like cloned cell line, U1, which produces very low levels of HIV-1 at baseline. The stimulation of viral production from this cell line occurs only if these cells are treated with granulocyte/macrophage colony-stimulating factor (GM-CSF) before treatment with LPS. This stimulation of HIV-1 production is correlated with an increase in the level of HIV-1 RNA and and activation of NF kappa B. LPS is not able to induce HIV-1 production in a cloned T cell line. The effect of LPS on HIV-1 replication occurs at picogram per milliliter concentrations and may be clinically significant in understanding the variability of the natural history of HIV-1 infection. PMID- 2193099 TI - Regulation of parasite-induced eosinophilia: selectively increased interleukin 5 production in helminth-infected patients. AB - Production of the eosinophilogenic cytokines interleukin 3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM-CSF), and IL-5 by mitogen stimulated peripheral blood mononuclear cells was compared between 11 noneosinophilic individuals and seven patients with helminth-induced eosinophilia. Both the kinetics and quantities of IL-3 and GM-CSF were similar in the two groups. In contrast, IL-5 production at both the protein and the mRNA level was markedly greater in the eosinophilic patients, an observation suggesting that IL-5 may be particularly important in mediating the selective eosinophilia seen in filarial and other helminth infections. PMID- 2193102 TI - A new chemiluminescence immunoassay for triiodothyronine and thyroxine: evaluation using quality control sera assayed in an interlaboratory survey. AB - A recently developed chemiluminescence immunoassay system (LIA-mat) for triiodothyronine and thyroxine, set up by Byk-Sangtec Diagnostica (Dietzenbach, Germany), has been evaluated and compared with radioimmunoassays and with a chemiluminescence enhanced enzyme immunoassay (Amerlite), using control materials circulated in a national interlaboratory quality control, as well as patient sera. The LIA-mat assays are competitive methods which use coated monoclonal antibodies and triiodothyronine- or thyroxine-ABEI (aminobutylethylisoluminol) conjugate as tracers. The working range of LIA-mat T3 (computed from the within assay precision profile) extended from 1.4 to 12.3 nmol/l; the between-assay precision was 8.1 - 19.3 CV%. Regression analysis of the LIA-mat T3 results (y) against the consensus means (x) of the participants in the national interlaboratory survey yielded: y = -0.14 + 1.05 x, r = 0.95. The working range of LIA-mat T4 extended from 33 to 515 nmol/l; the between-assay precision was 5.4 - 9.2 CV%. An excellent agreement was found between LIA-mat T4 results (y) and the consensus means (x) of the laboratories participating in the national interlaboratory survey (y = 3.79 + 1.02 x, r = 0.98). PMID- 2193100 TI - Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition. AB - A cell adhesion model was previously used to select a series of monoclonal antibodies (mAbs), which were subsequently found to recognize CD44/Pgp-1. Interest in these reagents increased with the finding that they totally inhibited production of lymphoid or myeloid cells in long-term bone marrow cultures. Further investigation has now revealed that hyaluronate is a potential ligand for CD44 and that hyaluronate recognition accounts for the adhesion between B lineage hybridoma and stromal cells. The hybridoma cells adhered to hyaluronate-coated plastic wells as well as to monolayers of stromal cells. The adhesion in both cases was inhibited by treatment with hyaluronidases, and did not require divalent cations. Addition of exogenous hyaluronate also diminished binding of lymphoid cells to stromal cells. One of several mAbs to Pgp-1/CD44 was particularly effective at blocking these interactions. Since hyaluronate and Pgp 1/CD44 were present on both cell types, experiments were done to determine the cellular location of interacting molecules required for the adhesion process. Treatment of lymphoid cells with an anti-Pgp-1/CD44 antibody was more inhibitory than antibody treatment of the stromal cells. Conversely, hyaluronidase treatment of stromal cells reduced subsequent binding more than treatment of the lymphoid cells. Adhesive interactions that involve hyaluronate and CD44 could contribute to a number of cell recognition processes, including ones required for normal lympho-hemopoiesis. PMID- 2193101 TI - Lipid IVA inhibits synthesis and release of tumor necrosis factor induced by lipopolysaccharide in human whole blood ex vivo. AB - Tumor necrosis factor (TNF) released by lipopolysaccharide (LPS)-stimulated mononuclear phagocytes is a critical mediator of sepsis. We examined the capacities of rough mutant Salmonella typhimurium LPS (Rc) and LPS partial structures lipid A, monophosphoryl lipid A (MPLA), lipid IVA, and lipid X to induce production of TNF in whole blood. Rc LPS (0.0001-10 ng/ml) produced a dose dependent release of TNF as determined by cytotoxicity of actinomycin D sensitized L929 murine fibroblasts. Lipid A, MPLA, lipid IVA, and lipid X exhibited decreasing capacities to stimulate production of TNF in whole blood, respectively. Fractional deacylation of LPS by incubation with acyloxyacyl hydrolase isolated from human leukocytes produced a reduction in the capacity of LPS to induce TNF release in whole blood. Maximal enzymatic deacylation reduced activity of LPS by greater than 100-fold. Coincubation with lipid IVA inhibited TNF release induced by Rc LPS or lipid A, but not by phorbol ester. In contrast, MPLA, lipid X, and deacylated LPS failed to inhibit LPS-stimulated release of TNF. Corresponding to the inhibition of the release of TNF protein, lipid IVA also inhibited the accumulation of TNF mRNA in LPS-stimulated mononuclear cells. These results suggest that lipid IVA may act as a competitive antagonist of LPS, perhaps at the receptor level. PMID- 2193103 TI - Enzyme immunoassay of human cholinesterase (EC 3.1.1.8). Comparison of immunoreactive substance concentration with catalytic activity concentration in randomly selected serum samples from healthy individuals. AB - We developed an enzyme immunoassay (ELISA) for quantitation of plasma cholinesterase substance concentrations in native plasma or serum samples. The ELISA assay is based on polyclonal (rabbit) antihuman cholinesterase and a highly specific monoclonal (mouse) antibody, with a commercially available peroxidase conjugated (rabbit) antibody directed against mouse immunoglobulins as the signal carrier. The detected serum cholinesterase substance concentrations (mean: 4.51 mg/l, SD: 0.90 mg/l) in randomly selected serum samples from 33 healthy individuals were closely and linearly related to the corresponding catalytic activity concentrations. PMID- 2193104 TI - Multicentre evaluation of the Boehringer Mannheim/Hitachi 717 analysis system. AB - We conducted an European multicentre trial to assess the performance of the new Boehringer Mannheim/Hitachi 717 analysis system. The photometer response was linear up to an absorbance of 2.8. The maximal CV of photometric imprecision was 0.5% for the wavelength pair 340/405 nm within the absorbance range 0.9 to 2.4. For the 13 analytes in our study, mean within-run imprecision was less than 2%, and mean between-day imprecision less than 2.5%. The results obtained with the Hitachi 717 instrument correlated closely with those of comparison instruments. Linearity for the various tests was high and exceeded the manufacturer's claims. No drift was detected during an 8-hour work period; carry over could not be detected under the chosen experimental conditions. The new instrument was readily accepted by the evaluators because of its ease of handling and simple daily maintenance. PMID- 2193105 TI - Phenylethylamine in the CNS: effects of monoamine oxidase inhibiting drugs, deuterium substitution and lesions and its role in the neuromodulation of catecholaminergic neurotransmission. AB - Phenylethylamine is present in brain in tiny quantities, it is heterogeneously distributed and present in synaptosomes, and it is synthesized and degraded very quickly. If deuterium is substituted for hydrogen on the alpha carbon of the side chain then it exhibits profound isotope effects to MAO and its penetration and persistence in the brain is considerably enhanced. In the presence of MAO-B inhibitors treatment with reserpine causes reciprocal changes to PE and DA suggesting a functional relationship between them and after unilateral lesions of the substantia nigra an ipsilateral reduction in striatal PE is seen suggesting again a co-relationship with DA. Following iontophoresis PE has been shown to exhibit indirect sympathomimetic effects but in addition when applied at low currents concurrently with DA or NA it causes post synaptically a substantial potentiation in the actions of the latter amines. As a result of this and other data PE has been proposed to be a neuromodulator of catecholaminergic transmission. PMID- 2193106 TI - Phenolsulfotransferase (PST) and PAPS in catecholamine metabolism in human tissues: an overview. AB - Sulfate conjugation in vitro was studied in a number of human tissues, such as the platelets, liver as well as in human foetal liver cells in culture. Essentially, the two enzymes involved in PAPS generation and PST were measured either singly or in combination, representing PAPS generation, PST and the overall three-step sulfate conjugation. These activities in the liver and platelets were comparable in magnitude. In the platelets, PAPS generation and PST activities showed a good correlation to the overall sulfate conjugation. With the expression of these activities in human foetal liver cells in culture, it is anticipated that such cells can be employed as model systems for the study of sulfate conjugation in man. PMID- 2193107 TI - Partial damage to nigrostriatal bundle: compensatory changes and the action of L dopa. AB - Parkinson's disease is associated with degeneration of the nigrostriatal bundle. However, the neurological symptoms that accompany this disease do not emerge until the degenerative process is almost complete. Early studies with animals models suggested that the extensive preclinical phase of Parkinsonism was due in part to the development of a compensatory hyperactivity within remaining dopamine containing neurons. Other studies suggested that systemic administration of L DOPA could reduce the neurological symptoms once they emerged by further increasing the availability of dopamine in striatum. Subsequent work has supported both hypothesis. PMID- 2193108 TI - Oxidative stress: a role in the pathogenesis of Parkinson's disease. AB - The degeneration of nigro-striatal dopaminergic neurons is considered to be a predominant pathogenetic factor of Parkinson's disease (PD). However, the etiology of this degeneration is not known. Hypotheses assume accumulation of endogenous and/or exogenous toxins as trigger of the disease. An increase in the concentration of free radicals has been suggested to be toxic to cells, especially when combined with certain metals like free iron or copper. The role of melanin in the degenerative process is not clear, but autoxidative reactions such as the oxidation of dopamine (DA) to melanin generating radicals and toxic metabolites seem to enhance the vulnerability of neurons in the substantia nigra (SN). Disappearance of melanin in the SN, increase of total iron and ferric iron, extreme decrease of glutathione (GSH) levels, reduced activity of enzymes involved in the detoxification of hydrogen peroxide, hydroxyl and superoxide radicals (peroxidases, catalase, glutathione peroxidase), an increase of monoamine oxidase B (MAO B) activity and the substantial increase of malondialdehyde, a marker of lipid peroxidation, in the SN seem to indicate a role of an oxidative stress syndrome in the SN causing or aggravating PD. PMID- 2193109 TI - Selectivity of melaninized nigra-striatal dopamine neurons to degeneration in Parkinson's disease may depend on iron-melanin interaction. AB - The recent studies on the chemical pathology of Parkinson's disease show selective increases of iron and lipid peroxidation and decreased glutathione (GSH) oxidizing capacity in the substantia nigra (SN). These changes are indicative of oxidative stress, possibly due to the accumulation of iron in the SN. It is the melaninized dopamine neurons that are vunerable to degeneration. The investigation of the interaction of iron with dopamine melanin demonstrates the presence of two relatively high affinity binding sites for 59Fe3+ on dopamine melanin. Interaction of Fe3+ with dopamine melanin results in potentiation of lipid peroxidation of rat cerebral cortex as compared to that induced by Fe3+. Only compounds with the ability to chelate iron are able to inhibit the binding of Fe3+ to melanin and the resultant lipid peroxidation. Therapeutic use of iron chelators, with the ability of crossing the blood brain barrier, as agents for retarding the oxidative stress and Parkinson's disease is envisaged. PMID- 2193110 TI - The effects of aging on MAO activity and amino acid levels in rat brain. AB - The possibility that age-related changes in amino acid levels in various rat brain areas might correlate with modifications of monoamine oxidase (MAO) activity, already found with aging, has been examined. Taurine, aspartic acid and glutamic acid levels were found to be unchanged or decreased with age, whereas GABA and glutamine concentrations increased or remained unchanged. Serine and glycine (except in pons-medulla) levels were found to be unaffected by age. The increase in total MAO activity with aging in some brain areas might contribute to the changes in amino acid levels. Likewise, the possible influence of age-induced changes in activity of various enzymes involved in H2O2 and NH3 detoxication and in amino acid biosynthesis on rat brain amino acid levels are considered. Oral administration of clorgyline or 1-deprenyl to young rats did not significantly modify the concentrations of most brain amino acids. PMID- 2193111 TI - From moclobemide to Ro 19-6327 and Ro 41-1049: the development of a new class of reversible, selective MAO-A and MAO-B inhibitors. AB - This study describes the serendipitous discovery of moclobemide, a short-acting MAO-A inhibitor which is in an advanced stage of clinical development as an antidepressant. The short duration of action of this MAO inhibitor containing a morpholine ring moiety is due to the complete reversibility (probably by metabolism of the inhibitory molecular species) of MAO-A inhibition. Since moclobemide is much more effective in vivo than expected from its in vitro activity, investigations to identify a possible metabolite(s) more active as MAO A inhibitor than the parent compound were carried out. The study of the MAO inhibitory characteristics of several known and putative moclobemide metabolites did not allow the identification of a potent MAO-A inhibitor but led to the discovery of Ro 16-6491, a potent MAO-B inhibitor of novel chemical structure. Systematic chemical modification of the aromatic ring system of Ro 16-6491 finally provided Ro 19-6327 and Ro 41-1049 which are highly selective and reversible inhibitors of MAO-B and MAO-A, respectively. Tritiated derivatives of Ro 19-6327 and Ro 41-1049 were used in binding studies to elucidate their mechanisms of action and to study their cellular distribution by quantitative enzyme radioautography. PMID- 2193112 TI - Involvement of neuropeptide Y in neuroendocrine stress responses. Central and peripheral studies. AB - Neuropeptide Y (NPY) is closely associated to stress-reactive structures in the central and peripheral nervous system. In the periphery, the peptide is colocalized with catecholamines in postganglionic sympathetic fibres and the adrenal medulla. In the brain, the paraventricular nucleus of the hypothalamus receives a dense innervation of NPYergic neurons, some of which also contain monoamines. With the use of a specific immunoradiometric assay, we have demonstrated that NPY is released into the peripheral circulation during psychological stress together with catecholamines. The postganglionic origin of the peptide was demonstrated by the activity of the nicotinic antagonist hexamethonium to attenuate the response. Adrenalectomy or insulin-induced hypoglycemia did not alter basal or stimulated NPY plasma levels, showing that the adrenal is not a major source of circulating NPY in the rat. Although NPY and noradrenaline are frequently released in parallel in various experimental conditions, a clear dissociation can be found in several cases, such as cold stress or the response to phentolamine, where no change can be seen in plasma NPY despite a large activation of noradrenergic terminals. Furthermore, the neuropeptide may play a role in stress-induced pathological states such as hypertension, since its release is greater in animals previously submitted to chronic stress and high-sodium diet. On the other hand, its role in the central nervous system control mechanisms of the stress response is far from being clear, but to understand the interaction of NPY we need a better knowledge of the role of noradrenergic neurons in the central control of the adrenocortical axis or sympathetic nervous system activity. PMID- 2193113 TI - Cefuroxime in total joint arthroplasty. Intravenous or in bone cement. AB - A prospective randomized clinical trial was performed in two centers to compare the effect of systemic cefuroxime and cefuroxime in bone cement in the prophylaxis of infection after total joint arthroplasty. In two comparable groups comprising 200 and 201 patients, there was no statistically significant difference in the incidence of superficial wound infection. The early deep infection rate was 1%, with no difference detected between the group that received antibiotic in bone cement and the group that received systemic antibiotic. There were no late deep infections. It is concluded that cefuroxime given systemically or in bone cement is an effective antibiotic in the prophylaxis of infection after total joint arthroplasty. PMID- 2193114 TI - Aspirin prophylaxis and surveillance of pulmonary embolism and deep vein thrombosis in total hip arthroplasty. AB - This is a prospective study of aspirin prophylaxis and thromboembolism surveillance in 159 patients having total hip arthroplasty by one surgeon at one institution. All patients had preoperative venous Doppler examination of the lower extremities and a ventilation-perfusion lung scan. Aspirin (650 mg) was given the night prior to surgery and continued at that dose twice per day. Venous Doppler examination was performed 10-14 days after operation. Asymptomatic pulmonary embolism was treated with oral anticoagulation only. There was a 12.6% incidence of pulmonary embolism, but only 1.9% of all patients developed a symptomatic pulmonary embolus. No patient had a fatal pulmonary embolus. No patient had a clinically evident deep vein thrombosis, and venous Doppler examination detected only nine patients with deep vein thrombosis (5.7%). The venous Doppler examination could not predict which patients would develop a pulmonary embolism. The authors could not determine a group of patients at high risk for the development of pulmonary embolism. There was no correlation between well-established "risk factors" and the development of pulmonary embolism. There was no correlation between the use of cemented or uncemented components and the development of pulmonary embolism. There were few complications of this prophylactic regimen of aspirin and surveillance. The authors believe this may be an acceptable prophylactic regimen for patients having total hip arthroplasty. However, the value of venous Doppler examination in the detection of deep vein thrombosis following total hip arthroplasty is uncertain. PMID- 2193115 TI - Management of stage I-II Hodgkin's disease in children. PMID- 2193116 TI - Interleukin-2 for metastatic melanoma: treating polyuria with insulin? PMID- 2193117 TI - Stage I-II pediatric Hodgkin's disease: long-term follow-up demonstrates equivalent survival rates following different management schemes. AB - The results of treatment of 171 children with stage I-II Hodgkin's disease from two institutions with differing approaches to management have been analyzed. At the Stanford University Medical Center/Children's Hospital at Stanford (SUMC/CHaS), pathologic staging followed by extended-field radiation alone or involved-field radiation plus combination chemotherapy have been cardinal to the management policy. At St Bartholomew's Hospital/The Hospital for Sick Children at Great Ormond Street (Barts/GOS), clinical staging only has been used over the last 10 years, and involved/regional-field radiotherapy used as the treatment of choice rather than extended-field radiotherapy. Some children at each institution received combined modality therapy as primary management. Relapse among children with stage I disease was a more frequent occurrence in the Barts/GOS series than in the SUMC/CHaS group. However, the survival rates from the two centers are identical, 91% at 10 years. The following scientific-philosophic question is asked: Should one maximally stage and treat all children to increase the likelihood of a high freedom from relapse (FFR; cure) rate, or is it acceptable to minimize the initial staging and treatment, realizing that a proportion of patients will fail and require salvage/rescue therapy? With the awareness of morbidity from pathologic staging and aggressive treatment, and the favorable survival data reported from specialized centers using differing approaches, treatment strategies should be directed toward the long-term goal of cure of disease with maximal quality of life. A multidisciplinary management philosophy undertaken at a center with extensive experience in pediatric Hodgkin's disease is important to achieving this goal. PMID- 2193118 TI - Increased risk of secondary acute nonlymphocytic leukemia after extended-field radiation therapy combined with MOPP chemotherapy for Hodgkin's disease. AB - The purpose of this study was to evaluate the influence of the number of mechlorethamine, vincristine, procarbazine, and prednisolone (MOPP) cycles and the extent of irradiation on the risk of secondary acute nonlymphocytic leukemia (SANLL) after a single combined treatment for Hodgkin's disease (HD). Between April 1972 and May 1980, 462 patients with HD clinical stage (CS) I, II, and III were prospectively treated with three or six cycles of MOPP and supra- and/or infradiaphragmatic irradiation (40 Gy). Four hundred forty-one patients achieved complete remission (CR). By January 1988, 237 patients had been followed-up in first CR for at least 10 years. Ten patients developed SANLL between the 34th and 123rd month of CR. The 15-year SANLL risk is 3.5% +/- 2.7%. Cox's stepwise regression analysis performed with all initial and treatment covariates (sex, age, histology, splenectomy, MOPP chemotherapy, and irradiation extent) showed that the only significant explanatory variable of SANLL risk was the irradiation extent (P less than .002). Using the log-rank test, SANLL risk ranged from 2.2% for supradiaphragmatic irradiation alone to 9.1% for subtotal (STNI) or total nodal irradiation (TNI) (P less than .001). These results strongly suggest that extended high-dose irradiation and MOPP chemotherapy should not be combined for the treatment of HD. PMID- 2193119 TI - A randomized trial comparing 12 weeks versus 36 weeks of adjuvant chemotherapy in stage II breast cancer. AB - A randomized trial has been performed in which women with axillary node-positive breast cancer were allocated to either a short intensive 12-week chemohormonal treatment consisting of cyclophosphamide, methotrexate, fluorouracil, vincristine, prednisone, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and tamoxifen (CMFVP plus AT) or 36 weeks of CMFVP. The median follow-up is 37 months. Of the 222 women randomized to the 12-week treatment, 113 (50.9%) have experienced either recurrence or death as compared with 90 patients (41.9%) in the 36-week treatment group. The corresponding 3-year relapse-free survivals are 55% and 64%, respectively, P = .003. Fifty-nine (26.6%) of the patients in the 12 week group have died compared with 46 (21.4%) of the 36-week group. The corresponding 3-year survival rates are 78% and 85%, respectively, P = .04. A Cox regression analysis showed an associated increased risk ratio for recurrence or death of 1.7, P = .003, and for death of 1.8, P = .017 in the 12-week treatment group compared with the 36-week group. Thus, this 12-week regimen of adjuvant chemohormonal therapy is inadequate treatment for women with axillary node positive breast cancer; possible explanations for this inferiority are its shorter duration and/or a negative interaction of tamoxifen on the chemotherapy. PMID- 2193120 TI - Imaging with indium111-labeled anticarcinoembryonic antigen monoclonal antibody ZCE-025 of recurrent colorectal or carcinoembryonic antigen-producing cancer in patients with rising serum carcinoembryonic antigen levels and occult metastases. AB - We tested whether nuclear imaging with indium111 (111In)-labeled murine monoclonal (MoAb) anticarcinoembryonic antigen (anti-CEA) ZCE-025 antibody could detect recurrent disease in patients with a rising serum CEA level but negative findings for computed tomographic (CT) scans of the abdomen and pelvis, chest radiograph, and colonoscopy or barium enema. Twenty patients with a history of completely resected CEA-producing adenocarcinoma (18 with colon cancer, one with breast cancer, and one with Hodgkin's disease) and a rising serum CEA level were given an intravenous infusion of 2 mg of 111In-labeled ZCE-025 mixed with 38 mg of unlabeled ZCE-025. Planar and single-photon emission CT (SPECT) scans were acquired at 72 and 144 hours, and in 19 of the 20 patients these were positive. Of those 19, 13 underwent exploratory surgery, and cancer was found in 10, and two had a diagnostic biopsy, which confirmed cancer. Three patients who had negative laparotomies and all four patients who did not undergo surgery or biopsy were followed radiologically. In all seven, cancer was subsequently detected at the sites suggested by the ZCE-025 scan. Thus, tumor was confirmed in all 19 patients with positive scans. Five of 13 patients who were explored benefited from the study and the exploratory laparotomy, as disease was entirely resected in four or was subjected to definitive radiation therapy to the pelvis in the fifth. In two additional patients who were not explored, MoAb imaging resulted in definitive therapy to regionally confined recurrent disease. 111In-labeled anti CEA MoAb ZCE-025 scanning in patients with rising CEA successfully imaged metastatic colorectal cancer that eluded detection by other methods and affected the care given to some. These results suggest an important role for 111In-labeled ZCE-025 scanning among patients with rising CEA and otherwise occult metastatic cancer. PMID- 2193122 TI - Treatment of malignant recurrent glioma by intra-arterial, infra-ophthalmic infusion of HECNU 1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl) urea. A phase II study. AB - 53 patients suffering from malignant recurrent glioma were treated with iterative arterial infusions of HECNU. The intra-carotid injections were performed below the ophthalmic artery. The response rate was 49% and the median survival was 8.5 months. The results differ substantially according to the histological subtype. The response rate was 33% for glioblastomas, 50% for anaplastic astrocytomas and 92% for malignant recurrences of low grade astrocytomas. The median survival was 4.5 months for glioblastomas and 18 months for anaplastic astrocytomas and malignant recurrences of low grade astrocytomas. Serious complications were a monocular blindness in 3 cases and a leucoencephalopathy in 6 cases. PMID- 2193123 TI - The influence of nipple stimulation at term on the duration of pregnancy. AB - The influence of nipple stimulation (NS) at term on the duration of pregnancy was investigated among low-risk gravidas in a randomized prospective study. A significant inverse relationship was found between the duration of pregnancy and both gestational age at recruitment and cervical (Bishop) score, although the influence of cervical score was quantitatively small. Nipple stimulation did not influence either the duration of pregnancy or the probability of having a cesarean section or an instrumental delivery. Patient compliance was, however, poor, which may in part account for these findings, as there was an inverse trend between the daily average duration of NS and the duration of pregnancy. PMID- 2193121 TI - Immunotherapy for malignant glioma using human recombinant interleukin-2 and activated autologous lymphocytes. A review of pre-clinical and clinical investigations. AB - Over the past few years, we and a number of other groups have conducted laboratory experiments and clinical trials of human recombinant interleukin-2 (rIL-2) alone or in combination with autologous 'activated' lymphocytes expressing in vitro tumoricidal activity in order to define toxicity and indicate its potential efficacy in patients with high-grade glioma. Because high rIL-2 concentrations can be attained with considerably less toxicity than with a systemic approach, all of the clinical trials, to date, have chosen a direct route; injecting lymphokine and cells into tumor tissue, the cystic cavity remaining after tumor excision, and/or neural parenchyma surrounding the site of tumor excision. While the rIL-2 therapies, as they have been applied in animal glioma models and patients, are safe, cerebral edema around the site of treatment has been a consistent finding. We have also seen, however, that steroid medications used by patients to control their cerebral edema may depress the anti tumor activity of rIL-2 by depressing the capacity of lymphocytes to develop normal LAK activity. Although none of the immunotherapies involving rIL-2 have produced cures, the fact that sustained clinical responses have been reported, suggests that such therapies may slow a recurrence of tumor at the site of treatment. Efforts to improve outcome from rIL-2--based immunotherapies for malignant glioma are continuing with manipulation of rIL-2 dosing and scheduling and also with combinations of rIL-2 and other recombinant cytokines. PMID- 2193124 TI - The risk of anesthesia in obese parturients. PMID- 2193125 TI - Cocaine and pregnancy--a lethal combination. AB - There are many pharmacologic agents that have an effect on pregnancy outcome. Evidence is rapidly being accumulated that cocaine use in the pregnant patient is detrimental to both fetal and maternal well-being. This paper is a review of current data to make the health care provider aware of the impact that cocaine use can have on the pregnancy. PMID- 2193126 TI - Neonatal ultrasound casebook. Ultrasound detection of cerebellum in occipital encephalocele. PMID- 2193127 TI - Breast milk for infants who cannot breastfeed. AB - Controversy exists regarding feeding the preterm infant. Milk banks serve as one source of human milk for preterm infants. Milk banks are discussed in terms of the benefits of human milk, the potential hazards, and ways that milk banks are attempting to avoid those hazards. This article focuses on the feeding needs of preterm and sick infants. A brief history of artificial feeding and milk banks is presented. PMID- 2193128 TI - Pediatric chance fracture. AB - A flexion-distraction injury of the first lumbar vertebrae (Chance fracture) in a child 4 years and 3 months old is discussed and the literature reviewed. Chance features are uncommon in children. This injury is seldom accompanied by a neurological deficit. Recommended treatment consists of early bed rest followed by the application of a hyperextension Risser cast. PMID- 2193129 TI - Isolated fracture of the coronoid process of the ulna: a case report and review of the literature. AB - A rare case of a fracture involving almost the entire coronoid process of the ulna (type III) is described. Open reduction and internal fixation of this fragment restored elbow stability and resulted in a painless range of motion lacking only 5 degrees of extension at 7 months. PMID- 2193130 TI - Isolated granulocytic sarcoma: report of a case in the oral cavity. PMID- 2193131 TI - Genetic aspects of nervous system development. PMID- 2193132 TI - Mantle zone lymphoma--is it an entity? PMID- 2193133 TI - Bovine spongiform encephalopathy: the need for knowledge, balance, patience, and action. PMID- 2193134 TI - Immunohistochemical demonstration of altered intracellular localization of the C Myc oncogene product in human colorectal neoplasms. AB - The distribution of the c-myc oncogene product p62 was examined by immunohistochemistry using the monoclonal antibody Mycl-9E10 in a series of 50 colorectal resections for carcinoma. The specimens were specially handled to ensure rapid fixation in formalin, and a significant improvement was shown in the quality and localization of staining compared with routinely handled specimens. Non-neoplastic mucosa showed the presence of nuclear staining of epithelial cells in 93 per cent of the samples, whilst all carcinomas showed cytoplasmic staining and infrequent nuclear staining. Adenomas showed an intermediate pattern, with significantly more frequent cytoplasmic distribution than non-neoplastic mucosa, but less than carcinomas. The results show that whilst fixation conditions are important in the immunolocalization of the c-myc protein product, there may be a consistent difference between non-neoplastic mucosa and carcinoma in the manner of association of p62 with the nucleus. PMID- 2193135 TI - Androgen receptor heterogeneity in human prostatic carcinomas visualized by immunohistochemistry. AB - Expression of the human androgen receptor was examined in 26 primary prostatic carcinomas by immunohistochemical staining with a polyclonal antibody reactive with the N-terminal domain of the human androgen receptor. Eighteen carcinomas showed homogeneous staining for the androgen receptor, whereas in seven cases a considerable heterogeneity in expression of the receptor was found. In one case, only a very limited number of immunoreactive tumour cells were detected. Comparison of androgen receptor expression with the tumour grading score, according to the MD Anderson grading system, revealed that the proportion of immunostained tumour cells and--to a lesser extent--the intensity of immunostaining were decreased in the more aggressive (grade III) tumours. The use of immunohistochemistry for detection of expression of androgen receptor in prostatic carcinomas may become a new and sensitive method for predicting prostatic tumour behaviour under hormonal therapy and prognosis. PMID- 2193136 TI - Active bile salt transport in the ileum: characteristics and ontogeny. PMID- 2193137 TI - Serological markers and celiac disease: a new diagnostic approach? AB - We analyze the diagnostic efficacy of two celiac disease serological markers: anti-gliadin (IgA and IgG class) and anti-endomysium IgA-class (EmA-IgA) antibodies applied to 336 serum samples from celiac patients on both gluten challenge and gluten-free diets, and a control group. The anti-gliadin and anti endomysium antibodies levels were significantly higher among the gluten-consuming celiac patients than in the other groups. The greatest efficacy in diagnosing celiac disease was achieved in the Ema-IgA class test. The IgA-class anti-gliadin antibodies proved to be more specific, with a higher positive test predictive value than the IgG-class anti-gliadin antibodies, whereas the latter proved to be more sensitive, with a higher negative test predictive value than those of the IgA-class anti-gliadin antibodies. Our results also demonstrate that the simultaneous assessment of anti-gliadin IgA- and IgG-class antibodies constitutes a valid test in selecting patients suspected of having celiac disease. In turn the EmA-IgA antibodies constitute a confirmative test for indication of an intestinal biopsy. PMID- 2193138 TI - Congenital hepatic fibrosis, cystic kidneys, mental retardation, and facial dysmorphy: a new report of an autosomal recessive syndrome. AB - This report concerns a boy with congenital hepatic fibrosis, cystic kidneys, mental retardation, and minor dysmorphic features. These symptoms have rarely been reported before and indicate that congenital hepatic fibrosis may not be a single clinical entity. PMID- 2193139 TI - Multiple intestinal stenoses and congenital self-healing histiocytosis in the same child. PMID- 2193140 TI - Neonatal sacrococcygeal teratoma: multiimaging modality assessment. AB - Neonatal sacrococcygeal teratoma (SCT) is a rare and potentially malignant tumor. We report on four cases of neonatal SCT, in which ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI) were used preoperatively to accurately establish the extent of the tumor and its relationship to the surrounding anatomic structures. This approach facilitates complete surgical resection and optimal outcome. PMID- 2193141 TI - Subsequent asynchronous torsion of normal adnexa in children. AB - Children who have suffered from ovarian torsion may be at increased risk for a repetitive event. Torsion in a normal adnexa may be due to excessive mobility resulting from congenitally long supportive ligaments. Oophoropexy or shortening of the ligamentous support of the remaining functional ovary after torsion is recommended in attempt to prevent a subsequent torsion. The evaluation of young females with abdominal pain should always include the consideration of ovarian torsion. Preoperative ultrasonography is not invasive and could lead to earlier operative intervention resulting in salvage of ovarian tissue. Observation in these same children may allow a torsed edematous ovary to convert to a nonviable necrotic tissue necessitating oophorectomy. Laparoscopy is useful in cases in which the diagnosis is unclear. PMID- 2193142 TI - N-methyl-D-aspartate antagonism and phencyclidine-like activity: a drug discrimination analysis. AB - The experiments examined the ability of competitive N-methyl-D-aspartate (NMDA) antagonists (CPP, CGS 19755), noncompetitive NMDA antagonists [phencyclidine (PCP), ketamine, MK-801], other putative excitatory amino acid antagonists (ifenprodil, PK 26124), and anticonvulsants (pentobarbital, chlordiazepoxide) to antagonize the discriminative stimulus (DS) effects of NMDA and to produce PCP like DS effects. Rats were trained to discriminate NMDA (40 mg/kg) from saline. The DS effects of NMDA were blocked by the competitive NMDA antagonists but were antagonized at best partially by the other drugs tested. The response rate decreasing effects of NMDA were attenuated to varied extents by both the competitive and the noncompetitive NMDA antagonists. Some competitive and noncompetitive NMDA antagonists partially mimicked NMDA. To further examine their NMDA-antagonist properties, the compounds were also tested for antagonism of NMDA (160 mg/kg)-induced lethality in mice; only the competitive and noncompetitive NMDA antagonists completely protected against NMDA-induced lethality. In rats discriminating PCP (2.5 mg/kg) from saline, the competitive NMDA antagonists produced less drug-appropriate responding than the noncompetitive NMDA antagonists but more than was produced by the other drugs tested. The extent to which compounds antagonize behavioral effects of NMDA and produce PCP-like DS effects may depend partly on the effect measured and on the component of the NMDA receptor complex with which they interact. Although the competitive NMDA antagonists were more effective in blocking NMDA than the other drugs tested, they failed to act as pure antagonists of the DS effects of NMDA. PMID- 2193143 TI - Axonal guidance by an avoidance mechanism. AB - 1. On a substrate consisting of alternating lanes of anterior and posterior tectal membranes, temporal retinal axons have a strong tendency to grow on the lanes of anterior membranes and to avoid the lanes of posterior membranes. 2. Temporal axons do extend neurites on posterior material, and in equivalent numbers and lengths to that of anterior membranes if the substrate consists of pure anterior or posterior membranes. 3. Inactivation of posterior membranes by heat or the enzyme phosphatidylinositol-specific phospholipase C (PI-PLC) abolishes their ability to induce the avoidance reaction of temporal axons. It is concluded that the posterior membranes contain a repulsive component for temporal retinal axons. 4. Growth cones growing on anterior membranes, which encounter posterior membranes at the strip boundary, in general do not become reduced in their growth rate. 5. These results are most easily explained by a "gradient reading model" similar to chemotaxis where the steering of a growth cone is independent on the growth rate. 6. According to the model, a gradient of a guiding component outside the growth cone is transformed into an internal gradient which gives the growth cone its directionality. 7. Other models like growth inhibition cannot be ruled out but need at least two additional assumptions like habituation for growth on the putative posterior inhibitory substrate and a strong local restriction of the inhibitory effect within the growth cone which contacts the posterior material. PMID- 2193144 TI - Early events in the development of Drosophila peripheral nervous system. AB - 1. We have analysed the development of the larval PNS of Drosophila, with the aim of understanding the genetic programme that underlies this development. 2. The achaete-scute gene complex (AS-C), which is required for the development of the adult PNS, is also necessary for the larval PNS. The analysis of different AS-C lesions shows that the larval PNS results from the superimposition of two independent subpatterns, each of which depends on one AS-C gene. 3. The analysis of the two subpatterns reveals hidden homologies between the very different arrangements of sense organs observed on different segments, suggesting that the initial pattern is the same in all segments and is later modified in the different segments. 4. The early arrangement of sensory mother cells can be visualised in a special transgenic line, A37. In this line the initial repetitive pattern inferred above can be directly observed. Furthermore this line makes it possible to decide whether a given mutation acts on the very early steps of the PNS development (determination) or at later stages (differentiation). 5. The line A37 has been used to show that mutations that reduce the PNS such as AS-C- or da- alter the very first steps of the process, while mutations which result in a hypertrophied PNS such as N seem to alter a subsequent step. We end up with an overview of the genetic operations that generate the arrangement of sense organs and sensory neurons. PMID- 2193145 TI - Cell-cell interaction during synaptogenesis. AB - 1. Neuromuscular synapse formation was studied using nerve and muscle cells dissociated from Xenopus embryos and kept in culture for 1 to 3 days. Within a few minutes of manipulated contact with isolated cholinergic neurons, miniature endplate potential-like depolarizations (MEPPs) due to spontaneous release of acetylcholine (ACh) from the neurons were detected in the muscle cells. 2. Addition of an antibody to a frog neural cell adhesion molecule (anti-NCAM) into the culture medium of nerve-muscle co-cultured for 1-3 days decreased the percentage of functional nerve-muscle contacts. 3. Acute exposure to anti-NCAM (1 hour) inhibited significantly muscle cell contact-triggered ACh release from initially identified cholinergic neurons. 4. Lysed muscle cells manipulated into contact with neurons induced ACh release, whereas lysed neurons did not, suggesting the presence of specific molecules on the muscle cell membrane capable of triggering ACh release from the cholinergic neuron. 5. Transient appearance of electrical coupling was detected between neuronal soma and muscle cell, suggesting the possibility of exchange of modulators for the formation and maintenance of neuromuscular synapses. 6. Neuromuscular synaptogenesis constitutes a complex process where at least two different types of direct cell cell interaction seem to occur: a) cell surface molecule contact (and binding) for cell recognition and triggering of ACh release, and b) transient intercytoplasmic communication between the cells for possible passage of modulatory molecules. PMID- 2193146 TI - Microtubule-associated proteins and the determination of neuronal form. AB - 1. The assembly of microtubules is essential for the maintenance of both the extension and the radial symmetry of axons and dendrites. Microtubule-associated proteins (MAPs) are implicated in this function because they promote tubulin polymerization and because they appear to be involved in cross-linking microtubules in the neuritic cytoplasm. 2. In a variety of species high molecular weight MAP2 is found only in dendrites and MAP tau is found only is axons, indicating that certain MAPs are associated with specific aspects of neuronal morphology. 3. All neuronal MAPs that have been studied are under strong developmental regulation with either their form or abundance changing between developing and adult brain. In both rat and Xenopus the change from "early" to "late" MAP forms occurs concurrently with the cessation of axon and dendrite growth and the maturation of neuronal morphology. 4. In situations where neuronal growth persists in the adult, such as retinal photoreceptor cells and the olfactory system, "early" MAPs continue to be expressed in the adult brain. 5. These results implicate MAPs in neuronal morphogenesis and suggest that "early" MAPs are involved in axon and dendrite growth whereas the "late" MAPs are involved in the stabilization of their mature form. PMID- 2193147 TI - Segmentation and the development of the vertebrate nervous system. AB - 1. Recent experiments on the development of neural segmentation in chick embryos are reviewed. 2. Segmentation of the spinal peripheral nerves is governed by a subdivision of the somite-derived sclerotome into anterior and posterior halves. Migrating neural crest cells and outgrowing motor axons are confined to the anterior sclerotome as a result, in part, of inhibitory interactions with posterior sclerotome cells. 3. The sclerotomal distribution of certain molecules known to influence growing nerve cells in vitro, namely laminin, fibronectin, N CAM, N-Cadherin and J1/tenascin/cytotactin, suggest that these molecules play no critical role in determining the preference of nerve cells for anterior sclerotome. 4. Peanut agglutinin (PNA) recognises cell surface-associated components on posterior cells which, when incorporated into liposomes, cause the abrupt collapse of sensory growth cones in vitro. The PNA receptor(s) may be inhibitory for nerve cells in vivo. 5. The chick hindbrain epithelium is segmented early in its development. Each branchiomotor nucleus in the series of cranial nerves V, VII and IX derives from a pair of segments lying in register with an adjacent branchial arch. Neurogenesis of motor and reticular axons begins in alternate segments, suggesting parallels with insect pattern formation. PMID- 2193148 TI - Agrin-like molecules in motor neurons. AB - According to the agrin hypothesis molecules that mediate the nerve-induced aggregation of acetylcholine receptors and acetylcholinesterase on developing and regenerating skeletal muscle fibers are similar or identical to agrin, a protein extracted from the electric organ of marine rays. Here we present evidence that agrin is highly concentrated in the cell bodies of motor neurons and is transported to axon terminals which is consistent with the agrin hypothesis. PMID- 2193149 TI - A genetic model for the study of abnormal nerve-muscle interactions at the level of excitation-contraction coupling: the mutation muscular dysgenesis. AB - Excitation-contraction in muscle fibers are coupled through a complex mechanism involving multiproteic components located at a specialized cellular site, the triadic junction. Triads in normal muscle fiber result from the apposition of sarcoplasmic reticulum citernae and T-tubule and possess strikingly organized ultrastructural elements, bridging both types of membranes, the "junctional feet". Muscular dysgenesis in the mouse is characterized by total muscle inactivity in the developing skeletal muscles due to excitation-contraction uncoupling. Triads have been found to be disorganized with no "junctional feet" and dihydropyridine (DHP) binding sites are decreased with no slow Ca2+ currents, suggesting a basic defect in the excitation-contraction coupling machinery itself. We may hypothesize that muscular dysgenesis results in a marked defect in a functional protein involved in the morphogenesis of the triad and/or directly involved in Ca2+ release for contraction. PMID- 2193150 TI - Role of adhesion molecules in the genesis of the peripheral nervous system in avians. AB - In vertebrates, the peripheral nervous system arises from the neural crest by a multistep process involving epithelium-mesenchyme interconversions and cell migrations. These successive events are associated with profound and controlled reorganization of the expression of both cell-cell and cell-substratum adhesion molecules responsible for the direct interaction of neural crest cells with their neighbours or the extracellular matrix. Thus, at the onset of emigration of neural crest cells from the neural tube, the cell-cell adhesion systems mediated by N-cadherin and N-CAM are lost by cells. This is accompanied by the complete reorganization of the extracellular matrix in the immediate environment of neural crest cells and by changes in cell shape. Later, as crest cells undergo migration towards their differentiation sites, they are found associated with fibronectin. Cell adhesion molecules are reaquired by neural crest cells following specific sequences as they coalesce into primordia of the various ganglia. In vitro, fibronectin constitutes the most appropriate substrate for migration of neural crest cells. The migration-promoting effect of fibronectin can be specifically inhibited both in vivo and in vitro by antibodies to fibronectin, integrin receptors, or by peptides containing the Arg-Gly-Asp-Ser sequence. Neural crest cells recognize two major adhesion sites along fibronectin molecules; these are the Arg-Gly-Asp-Ser sequence located in the medial part of the molecule and the CS1 site situated in the alternatively spliced IIICS region. These two sequences are required to permit full motile behavior of cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2193151 TI - Advantages of mouse models to study early steps of peripheral nervous system development. AB - The molecular mechanisms involved in the formation of mammalian peripheral nervous system remain largely unknown. Here we describe the new possibilities offered by mouse mutant analysis, new mouse in vitro models and the recent development of molecular genetic techniques which may permit analysis of the peripheral nervous system development at a level that was heretofore restricted to lower vertebrates. PMID- 2193152 TI - Influence of pregnancy on the course of malaria in mice infected with Plasmodium berghei. AB - The course of malarial infection was compared in pregnant mice inoculated with Plasmodium berghei at different stages of gestation. When 12-14 wk old, pregnant BALB/c mice were inoculated with 1 x 10(6) of P. berghei NK65-infected red cells at gestation day 0, 2, 4, 6, 8, 10, 12, 14 or 16, the mice inoculated on gestation days 6-12 expired 6.5 days after inoculation compared to 9.5 days in non-pregnant mice. Parasitemia in these pregnant mice increased rapidly on day 4 after inoculation and anemia also developed earlier on day 5. However, the degree of parasitemia and anemia in the terminal stage of infection in these pregnant mice was milder than that of non-pregnant controls. Blood urea nitrogen increased at the terminal stage although the degree of increase in mice inoculated on gestation days 6-10 was comparatively small. Pregnant malarial mice died earlier with less physiological changes than non-pregnant controls. It was concluded that pregnancy makes the host susceptible to physiological changes caused by malaria. PMID- 2193153 TI - Early crown-rump length. A good predictor of gestational age. AB - With the increased resolution of newer transabdominal and transvaginal imaging equipment, ultrasound is being used more frequently for the diagnosis of early pregnancy complications. Extrapolation of gestational age from early crown-rump lengths (CRLs) has been difficult because previously established tables of CRL versus gestational age have contained few measurements at less than seven to eight weeks from the first day of the last menses. Accordingly, the relationship between early CRL (in millimeters) and calculated menstrual age (CMA) (in days) in 36 patients with a known date of conception was studied with transvaginal sonography and found to have a linear relationship, defined by the equation CMA = 0.99 x CRL + 40.0 (r = .95, P less than .001). The relationship can be used to date pregnancies as early as 26 days after conception. PMID- 2193154 TI - Vaginal gamete intrafallopian transfer. Experience with 14 cases. AB - A procedure utilizing transvaginal aspiration of stimulated gametes followed by transcervical, ultrasound-guided catheterization of the tubal ostia was performed as a modification of the standardized gamete intrafallopian transfer (GIFT) technique. Among 14 patients with 16 cycles there were four normal, intrauterine pregnancies and one ectopic pregnancy. In two patients the beta-human gonadotropin level rose significantly and then started to fall; the patients aborted spontaneously. The procedure can be performed with a higher degree of patient acceptance than can traditional GIFT, and the success rate in this small series was promising. PMID- 2193155 TI - Umbilical cord cyst presenting as an omphalocele at 15 weeks' gestation. A case report. AB - A small, cystic structure was identified on a routine ultrasound scan performed for dating at 15 weeks' gestation. Originally it was thought to be an omphalocele, but further examination confirmed its origin in the cord several centimeters distal to the fetus. Close scrutiny of ultrasonograms is important since technical capabilities permit high-resolution scans during early gestation. PMID- 2193156 TI - Hydralazine induced lupus and Sweet's syndrome. Report and review of the literature. AB - This is the second case report of hydralazine induced Sweet's syndrome and lupus erythematosus. Our patient had the characteristic rash of Sweet's syndrome, confirmed histopathologically, as well as laboratory features consistent with drug induced lupus, including positive serum antinuclear and antihistone antibody tests. The association between these 2 clinical entities is discussed and a review of the literature is presented. PMID- 2193157 TI - Large vessel arterial thrombosis in systemic sclerosis associated with antiphospholipid antibodies. AB - A 69-year-old woman with systemic sclerosis developed thrombosis of each superficial femoral artery requiring above-knee amputations. On pathologic examination of the involved vessels, atherosclerotic changes were minimal and thrombus formation was the primary abnormality. The presence of antiphospholipid antibody suggested an acquired predisposition to vascular thrombosis. Prior reports of large vessel thrombosis in systemic sclerosis are reviewed. PMID- 2193158 TI - Bilateral spontaneous pneumothorax in systemic sclerosis--report of two cases. AB - We describe 2 patients with systemic sclerosis who developed bilateral spontaneous pneumothoraces. Though unilateral spontaneous pneumothorax has been described, the problem has not been emphasized recently and the complication of bilateral spontaneous pneumothoraces has not been documented. Treatment of the pneumothorax is difficult and reexpansion of the lung is slow. This complication is associated with a poor prognosis as both patients had severe respiratory impairment and one died shortly afterwards. PMID- 2193159 TI - Dystrophin expression and genotypic analysis of two cases of benign X linked myopathy (McLeod's syndrome). AB - DNA extraction and Southern blot analysis of two cases of McLeod's syndrome showed restriction fragments identical to normal controls using probes from the Xp21 (1-2) region, in contrast to striking deletions found in two other McLeod phenotypes studied in the USA. The McLeod locus is adjacent to Duchenne muscular dystrophy (DMD) and dystrophin immunocytochemistry showed that expression is normal in muscle from the two McLeod cases in spite of the mild DMD-like myopathy. PMID- 2193160 TI - Genetic services in Hong Kong. PMID- 2193161 TI - Structure and evolution of a multidomain multiphosphoryl transfer protein. Nucleotide sequence of the fruB(HI) gene in Rhodobacter capsulatus and comparisons with homologous genes from other organisms. AB - The gene order of the fructose (fru) operon and nucleotide sequence of the first gene (fruB(HI) of Rhodobacter capsulatus are reported, analyzed and compared with homologous genes from other bacteria, and the gene products are identified. Included within the region reported is a gene encoding a multiphosphoryl transfer protein (MTP) of the phosphoenolpyruvate:sugar phosphotransferase system (PTS). MTP consists of three moieties: a fructose-specific enzyme III (IIIfru)-like N terminal moiety (residues 1 to 143) followed by an FPr(HPr)-like moiety (residues 157 to 245) and an enzyme I-like moiety (residues 273 to 827). The enzyme III like moiety closely resembles the N-terminal 143 residues of the IIIfru-FPR fusion protein from Salmonella typhimurium (40.6% identity throughout its length) and the C-terminal 145 residues of the mannitol-specific enzyme II (IImtl) (37.8% identity throughout its length with the IIImtl moiety of IImtl). The FPr-like domain of MTP resembles the S. typhimurium FPr (42.4% identity) and the Escherichia coli or S. typhimurium HPr (38.8% identity). The enzyme I-like moiety resembles the E. coli enzyme I (38.9% identity). Predicted phosphorylation sites within the three functional units of MTP (His62 in the IIIfru-like moiety; His171 in the FPr-like moiety and His457 in the enzyme I-like moiety) were identified on the basis of sequence comparisons with the homologous proteins from enteric bacteria. The three functional domains of MTP are joined by two flexible "linkage" regions, rich in alanine, glycine and proline, which show 47% sequence identity with each other. They also exhibit a high degree of sequence identity with the linkage region of the mannose-specific enzyme III (IIIman) of the E. coli PTS as well as several other proteins of bacterial, eukaryotic and viral origin. At the RNA level, these linker regions formed hairpin structures with high (90%) G + C content. Analyses of the IIIfru-FPr fusion protein of S. typhimurium revealed that between the IIIfru and FPr moieties of this protein is a stretch of 142 amino acids that do not show homology to known PTS proteins. This region and the adjacent FPr-like region contain a sequence of 110 residues exhibiting 59% similarity to the receiver consensus motif defined by Kofoid and Parkinson. Because the Salmonella IIIfru-FPr fusion protein has been implicated in transcriptional regulation, this region of the Salmonella protein may prove to have regulatory significance.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2193162 TI - Construction of Escherichia coli amber suppressor tRNA genes. II. Synthesis of additional tRNA genes and improvement of suppressor efficiency. AB - Using synthetic oligonucleotides, we have constructed 17 tRNA suppressor genes from Escherichia coli representing 13 species of tRNA. We have measured the levels of in vivo suppression resulting from introducing each tRNA gene into E. coli via a plasmid vector. The suppressors function at varying efficiencies. Some synthetic suppressors fail to yield detectable levels of suppression, whereas others insert amino acids with greater than 70% efficiency. Results reported in the accompanying paper demonstrate that some of these suppressors insert the original cognate amino acid, whereas others do not. We have altered some of the synthetic tRNA genes in order to improve the suppressor efficiency of the resulting tRNAs. Both tRNA(CUAHis) and tRNA(CUAGlu) were altered by single base changes, which generated -A-A- following the anticodon, resulting in a markedly improved efficiency of suppression. The tRNA(CUAPro) was inactive, but a hybrid suppressor tRNA consisting of the tRNA(CUAPhe) anticodon stem and loop together with the remainder of the tRNA(Pro) proved highly efficient at suppressing nonsense codons. Protein chemistry results reported in the accompanying paper show that the altered tRNA(CUAHis) and the hybrid tRNA(CUAPro) insert only histidine and proline, respectively, whereas the altered tRNA(CUAGlu) inserts principally glutamic acid but some glutamine. Also, a strain deficient in release factor I was employed to increase the efficiency of weak nonsense suppressors. PMID- 2193163 TI - Scanning model for translational reinitiation in eubacteria. AB - Premature termination of translation in eubacteria, like Escherichia coli, often leads to reinitiation at nearby start codons. Restarts also occur in response to termination at the end of natural coding regions, where they serve to enforce translational coupling between adjacent cistrons. Here, we present a model in which the terminated but not released ribosome reaches neighboring initiation codons by lateral diffusion along the mRNA. The model is based on the finding that introduction of an additional start codon between the termination and the reinitiation site consistently obstructs ribosomes to reach the authentic restart site. Instead, the ribosome now begins protein synthesis at this newly introduced AUG codon. This ribosomal scanning-like movement is bidirectional, has a radius of action of more than 40 nucleotides in the model system used, and activates the first encountered restart site. The ribosomal reach in the upstream direction is less than in the downstream one, probably due to dislodging by elongating ribosomes. The proposed model has parallels with the scanning mechanism postulated for eukaryotic translational initiation and reinitiation. PMID- 2193164 TI - Flagellar hook and hook-associated proteins of Salmonella typhimurium and their relationship to other axial components of the flagellum. AB - Within the bacterial flagellum the basal-body rod, the hook, the hook-associated proteins (HAPs), and the helical filament constitute an axial substructure whose elements share structural features and a common export pathway. We present here the amino acid sequences of the hook protein and the three HAPs of Salmonella typhimurium, as deduced from the DNA sequences of their structural genes (flgE, flgK, flgL and fliD, respectively). We compared these sequences with each other and with those for the filament protein (flagellin) and four rod proteins, which have been described previously (Joys, 1985; Homma et al., 1990; Smith & Selander, 1990). Hook protein most strongly resembled the distal rod protein (FlgG) and the proximal HAP (HAP1), which are thought to be attached to the proximal and distal ends of the hook, respectively; the similarities were most pronounced near the N and C termini. Hook protein and flagellin, which occupy virtually identical helical lattices, did not resemble each other strongly but showed some limited similarities near their termini. HAP3 and HAP2, which form the proximal and distal boundaries of the filament, showed few similarities to flagellin, each other, or the other axial proteins. With the exceptions of the N-terminal region of HAP2, and the C-terminal region of flagellin, proline residues were absent from the terminal regions of the axial proteins. Moreover, with the exception of the N-terminal region of HAP2, the terminal regions contained hydrophobic residues at intervals of seven residues. Together, these observations suggest that the axial proteins may have amphipathic alpha-helical structure at their N and C termini. In the case of the filament and the hook, the terminal regions are believed to be responsible for the quaternary interactions between subunits. We suggest that this is likely to be true of the other axial structures as well, and specifically that interaction between N-terminal and C-terminal alpha-helices may be important in the formation of the axial structures of the flagellum. Although consensus sequences were noted among some of the proteins, such as the rod, hook and HAP1, no consensus extended to the entire set of axial proteins. Thus the basis for recognition of a protein for export by the flagellum-specific pathway remains to be identified. PMID- 2193165 TI - Screening methods in antineoplastic drug discovery. PMID- 2193167 TI - Expression of macrophage colony-stimulating factor gene in the mouse brain during development. AB - We have investigated the expression of macrophage-colony stimulating factor (M CSF) gene in mouse brain during development. Northern blot analysis of cerebral RNA evidenced a 4.5-kb M-CSF transcript from day 14 of gestation until 2 weeks after birth. The cell type responsible for this transcription was studied using in vitro cell cultures. The 4.5-kb M-CSF transcript was found both in astrocyte primary cultures and in immortalized astrocytic cell lines. M-CSF mRNA was also detected in lipopolysaccharide-stimulated brain macrophage cultures. These results suggest that M-CSF is involved in the outgrowth of microglia during ontogenesis. PMID- 2193166 TI - Controlled trial of megestrol acetate for the treatment of cancer anorexia and cachexia. AB - Preliminary information has suggested that megestrol acetate leads to appetite stimulation and nonfluid weight gain in patients with breast cancer, other cancers, and AIDS. Pursuant to this, we developed a randomized, double-blind, placebo-controlled trial of megestrol acetate in patients with cancer-associated anorexia and cachexia. We randomly assigned 133 eligible patients to receive 800 mg of megestrol acetate per day or a placebo. Patients assigned to megestrol acetate more frequently reported improved appetite (P = .003) and food intake (P = .009) when compared with patients receiving the placebo. A weight gain of 15 lb or more over baseline was seen in 11 of 67 (16%) patients receiving megestrol acetate compared with one of 66 (2%) given the placebo (P = .003). Patients receiving megestrol acetate reported significantly less nausea (13% vs. 38%; P = .001) and emesis (8% vs. 25%, P = .009). No clinically or statistically significant toxic reactions were ascribed to megestrol acetate, with the exception of mild edema. This study convincingly demonstrated that megestrol acetate can stimulate appetite and food intake in patients with anorexia and cachexia associated with cancer, leading to significant weight gain in a proportion of such patients. PMID- 2193168 TI - Kinanthropometry: roots, developments and future. PMID- 2193169 TI - Congenital renal abnormalities in infants with in utero cocaine exposure. AB - To determine the incidence of renal abnormalities among infants exposed to cocaine in utero, we performed ultrasound studies of the genitourinary tract in 100 consecutive infants admitted to the full-term nursery whose mothers had a history of cocaine use during pregnancy and/or a maternal toxicology screen was positive for cocaine. Mean gestational age of the newborns was 38.4 +/- 2.1 weeks. Mean birth weight was 2,846 +/- 561 gm.; 26% of the patients were less than 2,500 gm. and 18% were small for gestational age. Symptoms of drug withdrawal were present in 47 patients. Two newborns had murmurs consistent with a ventricular septal defect. On ultrasonography, 1 newborn had a unilateral multicystic/dysplastic kidney and 1 had kidneys that were 2 standard deviations below normal in size. Based on our results routine renal ultrasound studies do not appear to be indicated in full-term newborns exposed in utero to cocaine. PMID- 2193170 TI - Percutaneous decompression: treatment for respiratory distress secondary to multicystic dysplastic kidney. AB - Multicystic dysplastic kidney is a common renal anomaly in the newborn. Long-term problems, such as pain, infection, hypertension and neoplasm, although infrequent, have been reported. Acute, life-threatening complications resulting from the size of the affected kidney are rare and emergency nephrectomy has been the only reported effective therapy. We present a case of ultrasound-guided percutaneous cyst decompression used as definitive treatment of respiratory failure associated with multicystic dysplastic kidney. PMID- 2193171 TI - Elevations of cytokines interleukin-1, interleukin-2 and tumor necrosis factor in the urine of patients after intravesical bacillus Calmette-Guerin immunotherapy. AB - In an attempt to elucidate further the immunological mechanisms responsible for the effectiveness of intravesical bacillus Calmette-Guerin in the therapy of superficial urothelial bladder cancer, a prospective study was performed in which the urine of patients was examined before and after 6 intravesical instillations of bacillus Calmette-Guerin for the presence of the cytokines interleukin-1, interleukin-2 and tumor necrosis factor-alpha. Biological assays such as specific sandwich enzyme-linked immunosorbent assays were used for the analysis of each cytokine. Urinary titers of interleukin-1, interleukin-2 and tumor necrosis factor increased significantly after bacillus Calmette-Guerin instillation but showed inter-individual differences. The maximum of secretion into the urine was seen between 4 and 8 hours after the instillation, and titers returned to baseline values within 24 hours. The differences in 24-hour secretion between the bacillus Calmette-Guerin-treated (10 patients) and the control (10) groups were significant with respect to all cytokines as tested in both assays each, except for the interleukin-1 biological assay. These results reflect the strong inflammatory response in the bladder wall to bacillus Calmette-Guerin, in which the urinary secretion of the detected cytokines may be associated with the local tumor control. PMID- 2193172 TI - A randomized prospective comparison of oral versus intravesical and percutaneous bacillus Calmette-Guerin for superficial bladder cancer. AB - Reports of a dramatic decrease in tumor recurrence and regression of muscle invasive disease with oral bacillus Calmette-Guerin prompted us to conduct a randomized prospective comparison of oral bacillus Calmette-Guerin with the standard intravesical plus percutaneous therapy. Oral therapy consisted of 200 mg. Tice bacillus Calmette-Guerin 3 times each week. Intravesical and percutaneous Tice bacillus Calmette-Guerin at a dose of 50 mg. was given weekly for 6 weeks, at 8, 10 and 12 weeks, then at 6 months and every 6 months thereafter. Minimal side effects confirmed the safety of oral bacillus Calmette Guerin. Tumor recurrence was documented in 21 of 33 oral bacillus Calmette-Guerin patients (64%) and 18 of 55 (33%) who received intravesical plus percutaneous therapy (p less than 0.002, chi-square test). We were unable to demonstrate any antitumor activity of oral bacillus Calmette-Guerin in this study. PMID- 2193173 TI - Strategies for asymptomatic microscopic hematuria: a prospective study of 1,034 patients. AB - To establish strategies for treatment of asymptomatic microscopic hematuria we conducted a prospective study of 1,034 patients with this disease. The patients were examined by cystoscopy, urine cytology, abdominal ultrasound and excretory urography. On initial examination 30 highly significant lesions, including 24 cases of urological malignancies, 195 moderately significant lesions and 246 insignificant lesions were detected. In the remaining 563 patients no underlying lesion could be found. Of the 246 patients with insignificant lesions and 563 with unexplained asymptomatic microscopic hematuria followup was done in 421 at 6 month intervals for more than 1 year. A diagnosis became clear within 3 years in 22 patients, including 3 cases of bladder carcinoma and 1 of prostatic carcinoma. PMID- 2193174 TI - Common sense and carotid endarterectomy. PMID- 2193175 TI - Correlation of transcranial Doppler and noninvasive tests with angiography in the evaluation of extracranial carotid disease. AB - To evaluate the usefulness of transcranial Doppler sonography in determining severity of extracranial carotid disease, we compared transcranial Doppler, ocular pneumoplethysmography, Doppler spectral analysis, and duplex scanning data to information derived from cerebral angiography. Fifty-one consecutive patients with unilateral extracranial internal carotid artery stenosis or occlusion were selected. Transcranial Doppler indexes included the peak systolic flow velocity in the middle cerebral artery ipsilateral to the stenosed internal carotid artery (iMCAFV), the difference between the peak systolic flow velocities in the middle cerebral artery ipsilateral and contralateral to the stenosed internal carotid artery (dMCAFV), and the peak systolic flow velocity in the anterior cerebral artery contralateral to the stenosed internal carotid artery (cACAFV). The minimal residual lumen determined angiographically was used as the index of internal carotid artery stenosis. Linear regression analysis with minimal residual lumen as the dependent variable and transcranial Doppler and noninvasive tests as independent variables showed the following correlation coefficients: (1) dMCAFV and cACAFV, R2 = 0.3170; (2) ocular pneumoplethysmography, R2 = 0.4798; (3) dMCAFV, cACAFV, delta ocular pneumoplethysmography, duplex scanning, and spectral analysis R2 = 0.6382; (4) ocular pneumoplethysmography, duplex scanning, and spectral analysis, R2 = 0.6491; (5) iMCAFV, no association. These results were supported by sensitivity and specificity as well as bivariate analysis. We conclude that transcranial Doppler did not significantly add to the information obtained by our noninvasive battery of tests in the evaluation of unilateral extracranial carotid disease. PMID- 2193176 TI - The vascular endothelial cell as a vehicle for gene therapy. AB - Increasing knowledge that has accumulated during the past decade reveals that the endothelial cell plays a far larger role than that traditionally assigned to it, namely maintenance of the fluid state of the blood. Unraveling the complex interreactions of the endothelial cell with the other cellular and molecular components of the arterial wall, as well as with the blood and its cellular and particulate components, is leading to better understanding of anastomotic hyperplasia and recurrent stenosis after endarterectomy and balloon angioplasty. More recently with the newly acquired techniques of inserting genetic material into the vascular endothelial cell many new therapeutic possibilities may be developed. Important to the technique of seeding vascular grafts, and the possible use of the genetically modified endothelial cell for gene therapy systems, are the needs to identify the origin of the cell originally seeded and ways to increase their number. Retroviral vectors and genetically conferred antibiotic resistance provide these means. PMID- 2193177 TI - Simultaneous occurrence of superficial and deep thrombophlebitis in the lower extremity. AB - Forty-two consecutive patients diagnosed with superficial phlebitis were seen during a 5-year period. Thirty-five of the 42 patients were outpatients. The diagnosis of superficial phlebitis was made by the presence of palpable subcutaneous cords in the course of the greater saphenous vein or its tributaries in association with tenderness, erythema, and edema. The presence of concurrent deep venous thrombosis (DVT) was assessed by impedance plethysmography in 37 patients, compression venous ultrasonography in 3 patients, and venography in 8 patients. Five of the 42 patients (12%) had DVT. Four of these five patients had a positive impedance plethysmographic or ultrasonographic test result followed by a confirmatory venogram. The fifth patient had a positive ultrasonographic test result, but no venogram was performed. Two of the five patients had clots that involved the popliteal or femoral veins. Four of 23 patients (17%) with superficial phlebitis at or above the knee had DVT. Only 1 of the 19 patients (5%) with superficial phlebitis below the knee had DVT. Three of the five patients with both superficial phlebitis and DVT had undergone surgery recently. All but 3 of the 42 patients (93%) had varicose veins. No patients had clinically apparent pulmonary emboli. DVT occurred in 17% of the patients with above-knee extension of the superficial phlebitis. In the clinical management of superficial lower-limb thrombophlebitis, noninvasive tests should be performed to guide therapy. When superficial phlebitis develops after recent surgery or the superficial phlebitis extends above the knee, diagnostic surveillance should be especially strict. When the noninvasive test results are equivocal, phlebography is indicated to rule out DVT. PMID- 2193178 TI - The correlation of epidermal growth factor with invasion and metastasis in human gastric cancer. AB - We examined the localization of epidermal growth factor (EGF) in 185 specimens of primary human gastric cancer using the avidin-biotin peroxidase complex immunohistochemical method on formalin-fixed paraffin-embedded sections. Thirty four per cent of the gastric cancer specimens were positive for EGF, which was mainly located in the cytoplasm of the cancer cells and occasionally in the stromal cells, but was not detected in non-cancerous gastric epithelium. Moreover, the presence of EGF in gastric cancer was correlated with gastric wall invasion and lymph node metastasis. EGF was found more often in advanced cancers than in early ones (p less than 0.01), and also more often in cancers with lymph node metastasis than in those without (p less than 0.05). The five-year survival of patients with EGF-positive tumors was worse than that of patients with EGF negative tumors (p less than 0.05). The presence of EGF in human gastric cancer may thus represent higher malignant potential. PMID- 2193179 TI - Expression of human epidermal growth factor and its receptor in esophageal cancer. AB - The expression of human epidermal growth factor (hEGF) was examined immunohistochemically in 86 esophageal cancer lesions, comprising 67 primary tumors and 19 metastatic lymph nodes. In the normal esophagus, the parabasal and intermediate cell layers showed a weak expression of hEGF, however, hEGF-positive tumor cells were detected in 62 (92.5 per cent) of the 67 primary esophageal carcinomas and in 18 (94.7 per cent) of the 19 metastatic lymph nodes. In this study, the immunoreactivity of hEGF was classified into 4 grades according to the number of stained tumor cells. A significant correlation was observed between the histologic type and the grade of hEGF immunoreactivity (Chi-square test, p less than 0.01). hEGF immunoreactivity in well differentiated squamous cell carcinomas was significantly higher than in other squamous cell carcinomas, although there were no correlations between other pathological findings and hEGF immunoreactivity. Patients with hEGF immunoreactivities of grades II or III had much worse prognoses than those with grades 0 or I (p less than 0.05). In 22 esophageal carcinomas and 10 normal esophageal mucosae, EGF receptor (EGFR) contents were measured by the competitive binding assay. The average EGFR content (101.3 +/- 35.7 fmol/mg protein, mean +/- SE) of the esophageal carcinomas was significantly higher than that (5.3 +/- 1.2) of the normal esophageal mucosae (p less than 0.05). Moreover, in hEGF negative tumors, EGFR contents were lower than in hEGF positive tumors. These results suggest that hEGF and EGFR show increased production in squamous cell carcinomas and could to be useful prognostic factors in patients with esophageal cancer. PMID- 2193180 TI - Squamous cell carcinoma of the thyroid--a report of three cases. AB - Three cases of squamous cell carcinoma of the thyroid are reported herein. In all cases, the carcinoma occurred in old age and was characterized by a rapidly growing tumor, usually associated with dyspnea and dysphagia. The prognosis of all 3 cases was poor, with a mean survival of only 6.3 months. Although squamous metaplasia is an accepted etiology of this disease, clinical investigation of the cases presented here does not favor it in consideration of the clinical features of papillary carcinoma of the thyroid with squamous metaplasia. The histological findings of our cases revealed areas of cystic formation, suggesting that some of these carcinomas may be derived from remnants of embryonic origin. PMID- 2193181 TI - A case of adenomatosis coli complicated with malignant lymphoma of the spleen. AB - A case of adenomatosis coli complicated with malignant lymphoma of the spleen is described herein. An increase in the serum lactic dehydrogenase level of a 50 year old female was noted 9 years after she underwent a total colorectal resection for adenomatosis coli complicated by cancer. A tumor was observed in the spleen on CT and ultrasonography, and a diagnosis of malignant lymphoma was subsequently made by biopsy. At the time of splenectomy, no extension of the tumor was observed in any other organs and it was found histologically to be large cell type follicular lymphoma. A review of the 903 patients with adenomatosis coli documented in Japan revealed the occurrence of mesodermal malignant tumors to be considerably high. Hence, adenomatosis coli appears likely to be a causative factor in malignant lymphoma of mesodermal origin. PMID- 2193182 TI - Metabolic changes following gastroplasty in Prader-Willi syndrome--a case report. AB - A vertical banded gastroplasty was performed in an adult female patient with Prader-Willi syndrome in an attempt to prevent the metabolic deterioration caused by polyphagia. After her operation, the patient felt satiated with the scheduled amount of food and one month later, her fasting blood sugar concentration (FBS) decreased from 521 to 125 mg/dl, and her urinary sugar excretion (US) from 257 to 9 g/day. Both glucose tolerance and insulin secretion were also improved. However, these parameters subsequently became worse after dietary control was lost since the surgical procedure alone was unable to continue to suppress the insatiable desire to eat food. Both her glucose tolerance and insulin secretion by the 31st postoperative month were better than before the surgery, but worse than at one month after the surgery. At the end of the surgery, but worse than at one month after the surgery. At the end of the 34th postoperative month, even under the temporary administration of 0.625 mg/day of glibenclamide, her FBS was 158 mg/dl and US, 38.1 g/day. Her body weight had also increased to over her preoperative value. Based on these results, we conclude that the effect of gastroplasty to prevent metabolic deterioration in our patient with Prader-Willi syndrome gradually diminishes. PMID- 2193183 TI - [Medical and social issues in kidney transplantation]. PMID- 2193184 TI - [Study on urinary low molecular protein and enzyme in primary vesico-ureteral reflux patients]. AB - Urinary beta-2-microglobulin (beta 2-MG), urinary N-acetyl-beta-D-glucosaminidase (NAG), urinary creatinine (Cr) and serum creatinine level were measured in 79 patients with primary vesico-ureteral reflux. Comparing the data between conservatively treated group and operated group, between pre and post operation, we obtained the following conclusions: 1. From urinary beta 2-MG and NAG, renal tubular damage tended to increase in both conservatively treated group and operated group in proportion to the grade of reflux. But the degree of tubular damage was more severe in the conservatively treated group than in the operated group. 2. Tubular reabsorption ability was lower in the operated group than in the conservatively treated group. 3. In patients with severe tubular damage, improvement of tubular function was seen at the early stage after operation. 4. Anti-reflux operation was shown to be effective even in improving glomerular function. PMID- 2193185 TI - [Organ-sparing operations and the time of healing of duodenal ulcers (review of the literature)]. PMID- 2193186 TI - [Clinical significance of duodenogastric reflux (review of the literature)]. PMID- 2193187 TI - [Malignant tumors of the small intestine (review of the literature)]. PMID- 2193188 TI - [Effect of inguinal herniotomy on the functional status of the testis (review of the literature)]. PMID- 2193189 TI - [Selection of the method of reoperation after closure of perforated duodenal ulcer]. AB - The work deals with the study of the fate of patients who underwent closure of a perforated opening in a duodenal ulcer. In 27-53% of such patients subsequent nonoperative treatment was ineffective and they were subjected to reoperation: resection of the stomach or vagotomy. After comparative evaluation of these two reoperations on the grounds of the clinical data and the secretory and evacuating function of the stomach which had been operated on, the authors give preference to selective proximal vagotomy as an operation that is more physiological and devoid of the short-comings of gastric resection. PMID- 2193190 TI - [Treatment of peptic ulcer hemorrhage with leucine enkephalin analog dalargin]. AB - The article discusses treatment of 72 patients suffering from duodenal ulcer complicated by bleeding with the Soviet-made preparation Dalargin which is a synthetic analogue of leucine-enkephalin. The preparation was infused intravenously in a dose of 3 mg in physiological solution once daily. No other additional antiulcerative agents were give. The diagnosis was established on the basis of endoscopy. Dalargin led to cicatrization of the ulcers in 20.3 days in 60% of patient, obvious positive dynamics was noted in 32% of patients; in 8% of patients Dalargin proved ineffective. Basal hydrochloric acid secretion reduced by 56% during treatment. PMID- 2193191 TI - [Surgical treatment of bleeding gastroduodenal ulcers]. AB - The active-temporizing tactics accepted in the clinic, which is based on determination of the indications for operative treatment according to the endoscopic classification, abandonment of hemostatic therapy for elderly and senile individuals, active antiulcerous therapy, and consideration for immunological reactivity made it possible to reduce total mortality among patients with ulcerous gastroduodenal bleeding from 12.6% to 4.5%. PMID- 2193192 TI - [Invagination small-intestinal anastomosis in peritonitis and acute anemia]. PMID- 2193193 TI - Isolation and morphologic characterization in vitro of Schwann cells of the twitcher mouse. AB - Schwann cells were isolated and cultured from the twitcher mouse, an authentic model of human globoid cell leukodystrophy. We observed some difference in morphology and initial cell growth between the cells from suckling and adult mice. Initial growth was slower in homozygous and heterozygous twitcher (twi/twi; twi/+) cells than in normal cells (+/+) when cells were cultured from suckling mice. On the other hand, cell growth was initially accelerated in cells from adult twi/twi mice compared with adult twi/+ or +/+ animals. The yield of Schwann cells was much less from adults. In the cells from adult twi/twi, the perikaryon was swollen, and typical inclusions were easily recognized ultrastructurally, in particular after 14 days in vitro. However, only a few globoid cell leukodystrophy inclusions were detected in the cells from suckling twi/twi mice even after 28 days in vitro. The results indicate that Schwann cell pathology can be studied in twi/twi using an in vitro system and that twi/twi Schwann cells from suckling and adult mice have some differences in morphology as well as in the degree of initial growth. PMID- 2193194 TI - Localization of blood-retinal barrier breakdown in human pathologic specimens by immunohistochemical staining for albumin. AB - Human pathologic specimens from eyes with several different disease processes were immunohistochemically stained with antisera directed against rat or human serum albumin. In 33 eyes with no known ocular disease and no pathologic abnormalities, positivity was seen in the choroid and within retinal vessels, but not within the retina, except in one case in which focal staining in an area of outer retina was noted. In eyes with a history of ocular disease and/or pathologic findings, extravascular albumin staining was seen in areas of the retina generally corresponding to pathologic abnormalities. Albumin in the inner retina appeared to emanate from retinal vessels, but often collected along the internal limiting membrane. Staining in the outer retina was frequently demonstrated along the external limiting membrane, but in some cases, was also seen between the photoreceptor outer segments and within the retinal pigment epithelium. Eyes with primary retinovascular disease showed staining more commonly in the inner retina (77%) than the outer retina (38%) as would be predicted on theoretical grounds, whereas eyes with other disease processes showed no difference in frequency of staining between inner and outer retina. These data suggest that immunohistochemical staining of extravascular albumin is a useful technique for localizing breakdown of the blood-retinal barrier and is applicable to several disease processes. PMID- 2193195 TI - Speech analysis systems: a survey. AB - Recently developed, relatively inexpensive systems make digital speech analysis available to many teachers, clinicians, and researchers who have not had access to previous systems. Addressing these prospective users, we survey five microcomputer programs and two dedicated devices for recording, editing, and analyzing speech. We review the capabilities, requirements, and user interface of each system. We recommend considerations for prospective users and for developers of the next generation of such programs and devices. Finally, we briefly survey seven additional systems. PMID- 2193196 TI - Effect of verapamil on insulin-stimulated choleresis. AB - Insulin is one of several neurohumoral substances known to have a choleretic effect in vivo and in the isolated perfused rat liver. Infusion of insulin in the perfused rat liver preparation results in stimulation of bile acid-independent bile flow evidenced by increased bile flow, decreased bile acid concentration, and stable bile acid output. The mechanism of insulin-stimulated choleresis is unknown but may involve calcium as an intracellular second messenger. The present studies were performed to assess the role of membrane calcium channels in mediating choleresis and insulin-stimulated bile acid-independent bile flow in the in situ perfused rat liver. We have shown that verapamil, a specific calcium channel blocker, has no effect on bile flow, bile acid concentration, or bile acid output during bile acid-stimulated choleresis at a taurocholate infusion rate of 40 or 80 nmole/g liver/min. Insulin caused a significant increase in bile flow (18-30%) and a decrease in bile acid concentration (13-21%) without affecting bile acid output at a taurocholate infusion rate of 40 or 80 nmole/g liver/min. Verapamil failed to inhibit insulin-stimulated choleresis at a taurocholate infusion rate of 80 nmole/g liver/min. Although we observed an insulin-stimulated increase in bile flow and a decrease in bile acid concentration in the presence of verapamil at a taurocholate infusion rate of 40 nmole/g liver/min, these changes failed to reach statistical significance. We conclude that verapamil has no effect on choleresis or insulin-stimulated bile flow in the perfused rat liver and that the mechanism by which insulin promotes bile acid-independent bile flow is not mediated by verapamil-sensitive calcium channels. PMID- 2193197 TI - Epidemiology, advocacy and ideology in alcohol studies. PMID- 2193198 TI - Ethanol beverage anticipation: effects on plasma testosterone and luteinizing hormone levels--a pilot study. AB - Levels of plasma testosterone (T) and luteinizing hormone (LH) were evaluated in alcoholic and control subjects while they smelled a real beer and then drank a placebo beer which they believed contained alcohol. Plasma T and LH differed in the alcoholics and controls during beverage presentation and T levels also differed during drink consumption. Although these results suggest a role for conditioned responses, the lack of concordance between the hormone levels and psychophysiological responses or self-report desire to drink does not support a conditioning hypothesis that could account clearly for consumption behavior. Alternative hypotheses are discussed. PMID- 2193199 TI - Trauma metabolism and the heart. Uptake of substrates and effects of insulin early after cardiac operations. AB - In a controlled, randomized study the myocardial uptake/release of individual free fatty acids, glucose, lactate, pyruvate, alanine, and glycerol was studied 1 hour after completion of coronary operations. The effects of insulin were evaluated by means of a hyperinsulinemic "clamp" technique. No significant uptake of free fatty acids was found despite markedly elevated arterial concentrations (mean +/- standard error of the mean, 2.01 +/- 0.19 mmol.L-1), oleic acid, together with palmitic and linoleic acid, constituting 80% of the total plasma free fatty acid level. Insulin treatment (1 unit.kg bw-1.hr-1) prevented a further increase of the plasma free fatty acid level, observed concomitantly in the control group. Insulin affected all individual free fatty acids similarly. Changes in plasma free fatty acid levels occurring during the study and the corresponding myocardial uptake correlated (rS = 0.50 to 0.81). No significant uptake or release of glucose, lactate pyruvate, and glycerol occurred, whereas a myocardial release of alanine was seen. The heart and the concomitant leg uptake/release of glucose (rS = 0.40, p less than 0.05) and lactate (rS = 0.67, p less than 0.01) correlated. A substantial uptake of glucose was achieved and a more positive myocardial balance was obtained for alanine, lactate, and pyruvate with insulin. The changes in heart and the concomitant leg uptake/release correlated (glucose, rS = 0.62, p less than 0.01; lactate, rS = 0.64, p less than 0.01; pyruvate, rS = 0.71, p less than 0.01). It is concluded that the myocardial uptake of substrates during the first hours after coronary surgery is markedly abnormal with no uptake of free fatty acids or carbohydrates. These changes can be explained to some extent by the insulin resistance of trauma metabolism and can be modified by insulin treatment. PMID- 2193200 TI - Cardiovascular surgery prophylaxis. A randomized, controlled comparison of cefazolin and cefuroxime. AB - A prospective double-blind trial was performed at a tertiary care center to evaluate perioperative cephalosporin prophylaxis in cardiac operations. Patients were randomized to receive either cefazolin (n = 104) or cefuroxime (n = 109), the preoperative dose being given within 1 hour before the initial incision. Drugs were continued for 48 hours (cefazolin, 1 gm intravenously every 8 hours; cefuroxime, 1.5 gm intravenously every 12 hours). Postoperative infections were assessed by trained nurse clinicians, and data were analyzed by the intention-to treat principle. Sternal wound infections or mediastinitis occurred in one of 104 patients treated with cefazolin and 10 of 109 treated with cefuroxime (p = 0.01). Deep sternal wounds (including mediastinitis and sternal osteomyelitis) occurred in none of the cefazolin-treated patients and five cefuroxime-treated patients (p = 0.06). Although overall nosocomial infection rates were similar (16.3 versus 19.3 per 100), wound infection occurred somewhat more frequently with streptococci (groups B and D) in patients receiving cefazolin (four versus zero, p = 0.110); conversely staphylococcal infections were more frequent in the cefuroxime group (seven versus one, p = 0.066). Mean and median postoperative stay was 1 day shorter in the cefazolin group. In contrast to findings of a previous report, our data indicate that cefazolin prevented more sternal wound infections than cefuroxime, a finding that supports prophylaxis with a first generation cephalosporin. PMID- 2193201 TI - The Sellafield childhood leukemia cluster: are germline mutations responsible? PMID- 2193202 TI - A novel variant of the bcr-abl fusion product in Philadelphia chromosome-positive acute lymphoblastic leukemia. AB - Two patients with Philadelphia chromosome-positive acute lymphoblastic leukemia showed novel variants of the chimeric bcr-abl mRNA. The bcr-abl breakpoint region on cDNA derived from the chimeric mRNA was amplified using the polymerase chain reaction (PCR). Sequence analysis of the breakpoint-containing fragment showed that in both patients exon a2 of the abl gene was deleted, giving rise to an in frame joining at the mRNA level of 5' bcr sequences to the abl exon a3. These findings were confirmed by Southern blot analysis and cloning of chromosomal DNA. Protein studies showed a bcr-abl protein with heightened tyrosine kinase activity in blast cells of both patients: one of the P190 type, the other of the P210 type. The significance of these findings and the role of this new type of translocation in the disregulation of the abl gene are discussed. PMID- 2193203 TI - Two additional cases of t dic(9:12) in acute lymphocytic leukemia (ALL): prognosis in ALL with dic(9:12). AB - We report two occurrences of dic(9;12) in acute lymphoblastic leukemia and review previous cases. Cases of dic(9;12) share common features with cases of 9p and 12p rearrangements, but prognosis seems particularly good in cases of dic(9;12). The persistence of a specific dicentric in stable clones is remarkable and points to unusual centromeric behavior and/or marked selective advantage of the anomaly. PMID- 2193204 TI - Hepatotrophic growth factor in blood of mice treated with carbon tetrachloride. AB - The presence of a human hepatocyte growth factor (hHGF)-like DNA-synthesis promoter in platelet-poor serum of mice with liver injury was examined. Activity of the serum for stimulating DNA synthesis in cultured rat hepatocytes was low in untreated or vehicle-treated mice, but markedly increased 24 h after carbon tetrachloride administration and then dropped to normal levels prior to the peak of liver DNA synthesis. The effect of the serum was additive with the maximal effects of mouse and human epidermal growth factors, but not with that of hHGF. The growth-stimulating factor in the mouse serum, like hHGF, had affinity for heparin and was heat-labile. These results indicate that the level of a serum hHGF-like hepatocyte growth factor increased in mice treated with carbon tetrachloride prior to liver regeneration. PMID- 2193205 TI - Use of fetal-weight formulae in a community hospital. PMID- 2193206 TI - The importance of coding. AB - Medicare is very serious about claims being correctly coded. For those physicians participating with Medicare, claims will be denied if the ICD-9-CM code is not submitted with all the necessary digits. For those physicians who are non participating physicians with Medicare, they will first be notified if ICD-9-CM codes are not coded to the greatest level of specificity. After notification, if codes still lack the required digits for specificity, the physician can be fined up to $2,000 per incorrect code. PMID- 2193207 TI - Dizziness. A clinical perspective. AB - The clinical history and examination of dizzy patients leave much to be desired. Nevertheless, they are vital, as the selected treatment may be inappropriate and test data are likely to be meaningless unless interpreted in light of a thoughtful history and physical. Despite enormous variability in symptoms and signs of dizziness, the clinician must strive to categorize the patient's problems according to localization and etiology. The rules of thumb outlined above may assist in that enterprise. The remainder of this issue includes discussion of several sophisticated diagnostic tests aimed at understanding the nature of dizziness. Some of them are well established and some are investigational. Even with such a diagnostic battery, dizziness remains a perplexing problem. The complexity of the vestibular system and its interactions with visual input, somatosensory input, motor response, and conscious awareness continue to challenge our technology and our clinical acumen. PMID- 2193208 TI - A systematic approach to the dizzy patient. AB - The balance system is a complex integrated assortment of diverse nervous structures that may be organized hierarchically and analyzed according to known interactions and properties of the nervous system. From such a systems approach a variety of symptoms and signs may be predicted and evaluated, and a new pathologic nosology of dizziness may be derived. From this knowledge a more useful diagnostic method may be applied, and more appropriate therapeutic strategies designed. PMID- 2193209 TI - How do we use state of the art vestibular testing to diagnose and treat the dizzy patient? An overview of vestibular testing and balance system integration. AB - The physician must be the captain of the vestibular diagnostic team based on his interest, knowledge, and capability. It is not the battery of vestibular or etiologic function tests used that provides diagnostic answers. It is the intelligent application and use of the indicated vestibular tests that are practically correlated and clinically evaluated that will give the knowledgeable physician significant information. This can best be accomplished when testing is done in physical proximity to the responsible physician and when the tests used are knowledgeably ordered and evaluated. Under such circumstances, vestibular function testing is always cost-effective and therapeutically useful. PMID- 2193210 TI - Electronystagmography 1990. AB - Electronystagmography in 1990 should identify a vestibular abnormality with which to associate the clinical symptoms. The vestibular test battery method and interpretation reveals its application in neurotologic diagnosis. PMID- 2193211 TI - The sinusoidal harmonic acceleration rotary chair test. Theoretical and clinical basis. AB - Sinusoidal harmonic acceleration has become a common method used in diagnostic vestibular testing. When properly used, it can produce normal and abnormal patterns that can be interpreted in the context of the nature of the stimulus and the physiologic processes that describe the responses to it. Thus, the aim of this review is to present specific information regarding the sinusoidal harmonic acceleration stimulus and vestibular physiology in a way that will hopefully aid in test interpretation. PMID- 2193212 TI - Clinical value of sinusoidal harmonic acceleration test results. Site of lesion and side of lesion. AB - Sinusoidal harmonic acceleration tests can be used reliably to determine site and side of lesion. Results from 6000 patients collected over the past 10 years have shown that the temporal pattern of asymmetry can be reliably used to differentiate peripheral from central vestibular dysfunction. Peripheral cases tend to have a high level of asymmetry, with temporal regression to normal range, and a high correlation with patient symptoms. Central cases tend to have a low level of variable asymmetry and variable symptoms. In either case, phase can be abnormal or normal and cannot be reliably used to differentiate peripheral from central dysfunction. By combining phase and symmetry, the side of the lesion can be reliably determined. When phase is abnormal, asymmetry is toward the side of the lesion in 92 per cent of cases, whereas when phase is normal, asymmetry cannot be reliably used to determine side of lesion. SHA testing has contributed significantly to our clinical ability to fully evaluate the vestibular system and has become an indispensable part of the complete vestibular laboratory. It requires a relatively large patient load as well as software and hardware support to become a cost-effective utility. PMID- 2193213 TI - High-frequency autorotational testing of the vestibulo-ocular reflex. AB - Rotational testing is useful for clinical evaluation of vestibular dysfunction affecting the vestibulo-ocular reflex (VOR). Early applications relied on visual observation of nystagmus following turning. In modern use, control theory descriptors (e.g., gain and phase) are applied to patient data for comparisons with normal values. Motorized rotational chairs are used to passively oscillate patients with sinusoidal harmonic acceleration (SHA) stimulus profiles, usually at low frequencies (0.02 to 0.2 Hz). Changes in low-frequency phase and asymmetry, relative to normal values, provide useful indications of pathology. Vestibular autorotation testing (VAT) is a new, portable testing technique that utilizes microcomputers and patients' active head movements at high frequencies (2 to 6 Hz) to test both horizontal and vertical VOR responses. A head strap contains sensors and microelectronics for monitoring both head and eye movements. Higher-frequency VOR testing offers the advantages that the VOR is most active during locomotion at these frequencies and that other ocular motor systems are functionally insensitive above about 1 Hz. Results from VAT evaluation of patients with acute-stage Meniere's disease showed high vertical VOR gains, whereas patients receiving cisplatin chemotherapy showed pronounced low horizontal VOR gains and reduced phase lags. Practical experience in 4 years' clinical testing with the VAT has shown that this test is comfortable, efficient, clinically accurate, portable, and low cost, without requiring the dedicated, installed facility characteristic of other vestibular tests. PMID- 2193214 TI - Diagnosis of unilateral otolith hypofunction. AB - Asymmetric vestibular function is the basis of vertigo. Whereas caloric tests can identify unilateral peripheral loss or impairment of horizontal semicircular canal function reasonably accurately, there is as yet no single accepted test of unilateral otolith hypofunction. In some advanced vestibular laboratories around the world, new and perhaps diagnostically useful tests of otolith function are being devised. The physiologic basis and the present clinical applications of these tests are reviewed. PMID- 2193215 TI - Dynamic posturography in the diagnosis and management of dizziness and balance disorders. AB - This article reviews the basic concepts underlying the balance system, describes the information provided by dynamic posturography, and explains how the technique complements and expands on the information provided by traditional tests of vestibular function. PMID- 2193216 TI - Clinical application of dynamic posturography for evaluating sensory integration and vestibular dysfunction. AB - The assessment of sensory organization in balance control by dynamic posturography is unique compared with clinical maneuvers and other vestibular or neurologic testing. It was designed to isolate the relative contributions of visual, somatosensory, and vestibular feedback, and thus to assess the overall function of the balance control system in adaptively selecting between available sensory information for orientation cues to serve as a reference to earth vertical. Rather than serving as a test for specific pathologic conditions, the utility of posturography is in screening for balance disorders and in functionally defining different types of sensory deficits or central disorders. This functional information can be used to define restrictions or high-risk environments for patients, to guide rehabilitative balance therapy, and to monitor progression of recovery from a disease process. PMID- 2193218 TI - Imaging studies in patients with central vestibular disorders. AB - MR is the radiologic examination of choice when a patient's symptoms indicate the presence of some retrolabyrinthine pathology. CT dynamic studies now permit both heart and brain assessment for poor blood circulation problems of the hindbrain. PMID- 2193217 TI - Neuroradiology of vestibular pathways. AB - Comprehensive efficacious neuroimaging of the vestibular pathways requires cooperation and coordinated efforts between the otologist and the neuroradiologist to avoid duplication of expensive and sometimes invasive study. For peripheral lesions, for example, those of the labyrinthine organ, thin section CT is optimum as a first examination. For retrolabyrinthine lesions along nerve tracts or in the central pathway, MRI is preferred. When bone erosion occurs, CT can also be helpful in evaluation of the base of the skull to detect and define the extent of these lesions, for example, cholesterol granuloma and glomus tumor. PMID- 2193219 TI - Vestibular and other balance disorders in multiple sclerosis. Differential diagnosis of disequilibrium and topognostic localization. AB - Disorders of balance and equilibrium are common in multiple sclerosis (MS). This article reviews areas of central nervous system anatomy that may be involved in MS disequilibrium as well as the role of clinical examination, electrophysiologic testing, and magnetic resonance imaging in the diagnosis and assessment of vestibular dysfunction in MS patients. Relevant literature is reviewed and a case history is presented. PMID- 2193220 TI - Vascular compression syndrome of the eighth nerve. Clinical correlations and surgical findings. AB - A recently described syndrome, disabling positional vertigo (DPV), is characterized by persistent and progressive vertigo that is always associated with nausea and occasionally with vomiting; symptoms are made worse with changes in head position and are lessened with bedrest. Patients with DPV have abnormal results on vestibular testing and abnormalities in auditory nerve conduction as indicated by subtle but distinct alterations in brain stem auditory evoked potentials (BAEP). Microvascular decompression (MVD) of the vestibular nerve and, when indicated, the cochlear portion of the eighth cranial nerve has been highly successful in returning patients with DPV to normal lifestyles. Intraoperative monitoring of BAEP and auditory nerve compound action potentials have reduced the incidence of hearing loss, the major complication of MVD of the eighth nerve, to about 3 per cent. This article details the results of evaluating and treating 41 patients with DPV by MVD over a 12-month period and reports a success rate for this procedure in these patients of 73 per cent. PMID- 2193221 TI - Rehabilitation strategies for patients with vestibular deficits. AB - This article presents rehabilitation strategies for treatment of patients with vestibular deficits. Vestibular rehabilitation is an exercise-based approach designed to maximize central nervous system compensation for vestibular pathology. This paper reviews the physiologic rationale for an exercise-based approach and discusses specific assessment and treatment techniques involved in a vestibular rehabilitation program. PMID- 2193222 TI - [Phenotype and function of cells infiltrating rat renal allograft]. AB - Phenotype and function of graft infiltrating cells (GIC) from rat renal allografts were investigated in comparison with those of spleen (SP) cells, peripheral blood mononuclear cells (PBMC), and regional lymph node (LN) cells of the recipient. Relative proportions of all T cell, suppressor/cytotoxic T cell, helper T cell, and antigen-activated cell displayed significant increases in GIC during ongoing rejection assessed by flow cytometry. Cytolytic activity (using 51Cr release assay) of GIC on day 3 was much higher (20.2%) than those of SP (6.0%), PBMC (3.8%), and LN (3.2%) on BN target cells and this activity gradually increased during ongoing rejection up to 53.1% (GIC), on day 6. In vitro production of cytokines (IL-2, IL-3, gamma-IFN, and BSF-2) from these groups of cells were investigated. GIC demonstrated the most remarkable increases of cytokine production from day 3 to day 6. Especially, GIC on day 6 produced higher amount of BSF-2 compared with SP cells, PBMC and LN cells. These results demonstrated that alloactivated Th cells as well as Tc cells accumulated within the allografts and that the subtype of Th cells which produce BSF-2 preferentially assembled to the allograft. PMID- 2193223 TI - [Diagnosis of deep vein thrombosis by high resolution ultrasonography]. AB - Using high resolution ultrasonography (US), diagnostic accuracy of thrombi in each venous segment of lower limbs and qualitative evaluation of thrombi in deep vein thrombosis (DVT) were investigated. The subjects were 106 lower limbs in 81 patients. The thrombi in common femoral vein (CFV), were diagnosed by compression technique and, were qualitatively analysed by echogenicity and consistency. Venography was performed in 18 limbs and histologic tests of thrombi were made in 6 limbs. The total accuracy of US was 100% for diagnosis of DVT, but was 83% for diagnosis of its extent. The total accuracy of US in each segment was greater than 90%, but the sensitivity of iliac veins was less than 90%. The thrombi in CFV were divided into 3 types and 8 sub-types. Type A was homogenous, type B was heterogenous, and type C was contracted echo. The types of us were consistent with results of histologic tests. We concluded that high resolution US is available for screening test for diagnosis of DVT and that qualitative evaluation of thrombi by US is a useful clinical test for selection of more adequate treatments. PMID- 2193224 TI - [A case of mucinous cystadenocarcinoma of the gallbladder]. AB - A 69-year-old female with chief complaint of abdominal mass was admitted to Eiju General Hospital. CT and US showed the gallbladder as a multilocular mass associated with a gallstone. Abdominal angiography revealed no evidence of malignancy. She also had esophageal varices, and she underwent cholecystectomy, splenectomy, devascularization of proximal stomach, transection of the esophagus and pyloroplasty. Resected gallbladder had multilocular tumor and contained a large amount of mucus. Histopathological examination confirmed the diagnosis of primary mucinous cystadenocarcinoma of the gallbladder. PMID- 2193226 TI - Echocardiography (1). PMID- 2193225 TI - Biochemical correlates of the antitumor and antimitochondrial properties of gossypol enantiomers. AB - Racemic gossypol has been shown to have antitumor properties that may be due to its ability to uncouple tumor mitochondria or to its inhibitory effects on a variety of nonmitochondrial enzymes. We have studied the antimitochondrial and enzyme-inhibiting properties of gossypol in human carcinoma cell lines of breast (MCF-7, T47-D), ovarian (OVCAR-3) colon (HCT-8), and pancreatic (MiaPaCa) origin by comparing the effects of its purified (+)- and (-)-enantiomers. (-)-Gossypol shows up to 10-fold greater antiproliferative activity than (+)-gossypol in the cancer cell lines and in normal hematopoietic stem cells grown in vitro, with IC50 values ranging from 1.5 to 4.0 microM for the cancer cells and from 10 to 20 microM for the human marrow stem cells. As well, multidrug-resistant MCF/Adr cells appear more resistant to (-)-gossypol than their parental cell line. Electron microscopy indicates that the earliest ultrastructural change in tumor cells exposed to a cytotoxic (10 microM) concentration of (-)-gossypol is the selective destruction of their mitochondria. Consistent with this observation, 31P magnetic resonance spectroscopy detects pronounced changes in tumor cell high energy phosphate metabolism within 24 hr of (-)-gossypol treatment, manifest by 1.6- to greater than 50-fold differential reductions in the intracellular ratios of ATP/Pi, relative to (+)-gossypol-treated cell lines; the magnitude of these antimitochondrial effects correlates with the antiproliferative activity of (-) gossypol. Northern blot RNA analyses suggest that treatment with a 5-10 microM dose of (-)-gossypol induces a transient increase in the expression of heat shock gene products, particularly hsp-70 transcripts. The mean 5-fold increase in (-) gossypol-induced hsp-70 mRNA appears coincident with a comparable heat-stimulated increase in transcript levels, as compared with control or (+)-gossypol-treated cells. The enzyme-inhibiting properties of gossypol enantiomers were compared in cell-free assays measuring glutathione-S-transferase-alpha, -mu, and pi activities, calmodulin stimulation of cyclic nucleotide phosphodiesterase, and protein kinase C activity. Both enantiomers are near equivalent antagonists of calmodulin stimulation and protein kinase C activity, exceeding the potency of known inhibitors such as phenothiazines by as much as 50-fold. In contrast, (-) gossypol is a 3-fold more potent inhibitor of glutathione-S-transferase-alpha and -pi isozyme activity, resulting in IC50 values of 1.6 and 7.0 microM, respectively, for these two isozymes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2193227 TI - A history of dummies. PMID- 2193228 TI - Genetic engineering. Regulations breached. PMID- 2193229 TI - Paleoanthropology. Lining up the ancestors. PMID- 2193230 TI - New hominid skull material from the late Miocene of Macedonia in northern Greece. AB - Miocene hominoid material is very scarce and has previously only been reported as cranial fragments in the Old World. Here we describe a new specimen of Ouranopithecus macedoniensis, which consists of the right part of the face of an adult male with a portion of the frontal bone, a portion of the left part of the face and the maxilla with complete dentition except the right third molar. The characters of this specimen are not congruent with those of Sivapithecus and the pongids, but are more primitive and plesiomorphic for the recent hominid clade (Gorilla, Pan and Homo). The dental characters differ morphologically and metrically from those of the recent great apes and fit better with Australopithecus afarensis. Ouranopithecus now seems the best candidate forerunner of the Plio-pleistocene Homininae (Australopithecus and Homo). This specimen was discovered in September 1989, in the late Miocene deposits of central Macedonia (G.K., L. de B. and G.B.), and prepared by G.K. in Thessaloniki and G. Mouchelin in Poitiers. It comes from the new locality of Xirochori in the red sandstone of the Nea Messimbria formation. The fossil is the property of the University of Thessaloniki, Greece (catalogue number XIR-1). PMID- 2193231 TI - Direct and selective binding of an acidic transcriptional activation domain to the TATA-box factor TFIID. AB - The potent transactivation domain of the herpes simplex virion protein VP16 was used as a column ligand for affinity chromatography. VP16 binds strongly and highly selectively to the human and yeast TATA box-binding factors. Our results imply that the principal target for acidic activation domains is the TATA-box factor TFIID. PMID- 2193232 TI - An American perspective of the Nightingale legacy. AB - The work of Florence Nightingale has dominated not only the development of British nursing, but also affected nursing across the globe. She was particularly influential upon nursing in the United States of America. In this paper, the transfer of the Nightingale approach to the United States is explained. The early developments of nursing in North America, particularly at the time of the Civil War, and in public health nursing are applied. PMID- 2193233 TI - Nursing practice for catheter care. AB - Catheter care forms a frequent part of nursing practice, with the ever important need for nurses to be aware of current research evidence and developments. This paper critically reviews the literature and research evidence for catheter care and presents recommendations for nursing practice. PMID- 2193234 TI - [Operationalized diagnosis in psychiatry]. PMID- 2193235 TI - [Psychiatric diagnosis following the 10th revision of the International Classification of Diseases (ICD-10)]. AB - Following a historical overview the current state of development of psychiatric diagnostics is reported. Instead of intuitive clinical diagnoses an operational classification is aimed at. In the next few years WHO will introduce a new revision of the International Classification of Diseases. Development and structure of the psychiatric chapter V (F) of ICD-10 are described. Different versions of this chapter will appear for use in clinical psychiatry, scientific research and general medicine as well as for the use of the general practitioner. In characterizing the different subchapters some criticism is expressed, which has arisen in the Commission for Diagnoses of the German Society of Psychiatry (DGPN). Finally current studies concerning the practicability, reliability and validity of ICD-10 chapter V (F) are described. PMID- 2193236 TI - [Trials with ICD-10: results of a multicenter field study in German speaking countries]. AB - 134 clinicians in 10 centres participated in the WHO-initiated field trial in German-speaking countries of the provisional form of ICD-10, chapter V, clinical descriptions and diagnostic guidelines. 1778 diagnostic assessments were given for 90 cases. In general, the results show a comparatively high degree of acceptance of the new classification. Interrater-reliability coefficients are satisfactory. A high concordance of diagnostic categories between ICD-9, ICD-10 and DSM-III was found. PMID- 2193237 TI - [The abolition of psychopathology in the name of epiricism]. PMID- 2193238 TI - [The brains of the Vogt collection]. PMID- 2193239 TI - [Histological diagnosis of brain tumors: (10). Craniopharyngioma]. PMID- 2193240 TI - [Acoustic neurinoma in a child]. AB - A case is reported of acoustic neurinoma unrelated to Von Recklinghausens' disease in a child. A 14-year-old boy had suddenly become aware of impaired hearing associated with tinnitus, in August, 1988. He was admitted to our department in October, 1988. On admission, he had no neurological deficits except for right tinnitus. Acoustic tumor was found on air CT and MRI. Total removal of the tumor was achieved through a suboccipital craniotomy. The tumor had originated in the superior vestibular nerve. The size of the tumor was about 1 X 2 cm. The histological diagnosis was neurinoma. The facial and cochlear nerves were anatomically preserved. Twenty-two reported cases of acoustic neurinoma in children less than 15 years of age were reviewed. Based on these reports, it was concluded that acoustic neurinoma may grow rapidly in children, and they should be diagnosed and treated at an early stage. PMID- 2193241 TI - The role of high resolution ultrasound and MRI in the investigation of infants with macrocephaly. AB - External hydrocephalus was diagnosed using computed tomography in seven children presenting with macrocephaly. The value of different imaging techniques in distinguishing between subdural effusions and external hydrocephalus was investigated. High resolution ultrasonography combined with magnetic resonance imaging appeared to provide enough information to make a distinction between these two conditions. Radionuclide cisternography was still required to assess the flow pattern of the cerebrospinal fluid (CSF) which was important when placement of a lumboperitoneal shunt was considered. PMID- 2193242 TI - Intravenous immunoglobulin: a single-blind trial in children with Lennox-Gastaut syndrome. AB - The antiepileptic effect of intravenous immunoglobulin (Sandoglobulin, Sandoz) was investigated in Lennox-Gastaut syndrome by an add-on, placebo-controlled, single-blind trial. Ten patients, aged 4-14 years, with insufficient response to conventional anticonvulsive therapy received placebo and Sandoglobulin 400 mg/kg two times each with an interval of two weeks. The washout period was four weeks and the total observation period 14 weeks, during which parents daily registered number and type of seizures. EEG, in vitro lymphocyte transformation tests and concentrations of immunoglobulins including IgG subclasses were evaluated before and after active treatment. Two children showed an immediate reduction in their high-frequency and invariable seizure activity from 42% to 100% and a less abnormal EEG. In addition, general well-being and intellectual performance was improved. The strongest response was observed in one child with a concomitant finding of a low level of IgG2, the only abnormal immunologic test in this study. The remaining 8 children, who had either a high or a low but variable seizure frequency showed no immediate change as EEG and their general condition was unaffected. We conclude that intravenous immunoglobulin had an immediate and pronounced effect on break-through seizure activity and a simultaneous neurophysiologic effect in 20% of our patients with Lennox-Gastaut syndrome. The effect was not confined to patients with immunologic abnormalities. PMID- 2193243 TI - Protein structure: the primary substrate for memory. AB - The motility of protein structure, the existence of discrete conformational states, and the multifarious modes of supramolecular protein organization seem to underlie neuronal plasticity. These aspects of protein structure are surveyed from the viewpoint of their potential role in short-term and long-term memory. It is suggested that long-term memory may ensue from the remodelling of synaptic protein assemblies requiring extra copies of pre-existing proteins. PMID- 2193244 TI - [The use of echography and echo-guided fine needle biopsy in the preclinical diagnosis of renal neoplasms]. AB - During a 3 year period, 24 cases of renal cell carcinoma by means of ultrasonography have been observed. Seven of the 24 patients presented signs and/or symptoms of renal disease (29.2%); in 6 cases a malignant disease of unknown origin was suspected (25%) and in the other 11 the diagnosis was directed to gastrointestinal diseases (45.8%). The incidental finding of a renal malignant tumor by ultrasound in a high percentage of cases suggested an increasing use of this technique in hospitalized patients. PMID- 2193245 TI - [Effect of CDP-choline on senile mental deterioration. Multicenter experience on 237 cases]. AB - The efficacy of CDP-choline (1000 mg/die) administered for two 21-day treatment cycles, with a one-week wash-out period between them, was evaluated in out and in patients suffering from mild to moderate brain aging. The study was performed on 237 fully evaluable patients with the use of the reduced geriatric scale of Plutchik and al., for clinical evaluation of the symptomatology. The clinical data obtained demonstrate that treatment with CDP-choline is able to determine an improvement of symptomatology since the 1st cycle of therapy (p less than 0.001), and a further improvement in the 2nd cycle (p less than 0.001). Particularly, the therapeutic effect of the 1st cycle is persistent in the intermediate wash-out period (suspension of treatment) with a further decrease, of symptomatology regarding some items of Plutchik's scale (p less than 0.01). Finally, treatment with CDP-choline 1000 mg/die for two 21-day cycles in 237 patients suffering from brain aging determined a statistically significant improvement of the cognitive and behavioural parameters taken into consideration: independence/autonomous life; human relations/social life; interest and attentive capacity; individual behaviour. Therefore citicoline is confirmed as a valid therapeutic remedy for the clinical, functional and social recovery of these patients. PMID- 2193246 TI - [Simultaneous presentation of multiple myeloma and acute myelomonocytic leukemia in the absence of previous chemotherapy. Description of a case and review of the literature]. AB - A case of simultaneous occurrence of multiple myeloma and acute myelomonocytic leukaemia without previous chemotherapy is reported. A careful search of the literature disclosed 16 other cases of the same association. The possible relationships between these two haematopoietic neoplasms are discussed. On the literature and personal data, it is concluded that in course of multiple myeloma the association with an acute myeloblastic leukaemia is due to two possibilities: the first, more frequent, is the long-term effect of chemotherapy, while the second, rare, is that, by still unknown causes, a simultaneous neoplastic development of a plasma cell and myeloblastic clone occurs. PMID- 2193247 TI - [The practice of medicine in the Roman army: a synopsis]. PMID- 2193248 TI - [Ultrasonic evaluation of spontaneous and drug-induced cycles in a sterile population]. AB - The scope of this study was to correlate the size and number of growing follicles contemporeaneously in 106 spontaneous cycles and in 126 cycles induced by the administration of clomiphene, gonadotropins and LH-RH microinfusers, in a total of 149 sterile patients with a mean age of 30.2 years. The results have shown that maximum follicular diameter is significantly larger in drug-induced cycles in comparison to spontaneous cycles (p less than 0.05). Nonetheless, ultrasound examination alone is not sufficient to establish follicular development and the time for administering HCG in order to diminish the percentage of hyperstimulation syndromes. Additional biochemical and biological (E2) tests should therefore be performed, as well as a careful study of the endometrial response to induction therapy. PMID- 2193249 TI - [CA-125 serum levels in the diagnostic and clinical approach to ovarian cancer]. AB - The CA 124 serum level is a useful marker in monitoring epithelial ovarian carcinoma. More elevated serum levels when compared to the conventional cut-off (ie 35 U/ml), after the first surgical and/or chemotherapeutic approach, give evidence for the presence of an endocelomic and/or retroperitoneal tumour or are indicative of relapses. Also, they are well correlated with the endoperitoneal cytology pattern. Good correlation exists between the serological amount of CA 125 and tumoral mass before surgical removal whereas its efficacy in the differential diagnosis between primary ovarian tumours and metastatic disease ad well as its diagnostic specificity towards pelvic bulks, before removing them, is limited. Higher specificity seems to be obtained on increasing the cut-off threshold over 70 U/ml. PMID- 2193250 TI - [An atypical echographic aspect of endometriotic cysts. Description of a case]. AB - The paper reports an atypical ecographic pattern of endometriosic cysts. The large biometry and the presence of a septum which was more than 1 cm thick prevented the diagnosis of this ovarian pathology. The Authors agree that in similar cases it is important to limit the report to a mere description since it is impossible to identify the histological character of the ovarian mass. PMID- 2193251 TI - [Prenatal diagnosis of anatomo-pathologic aspects of 2 cases of sirenomelia]. AB - The antenatal echographic diagnostic aspects and anatomopathological features of two foetuses suffering from sirenomelia, or caudal pole regression syndrome, are examined. Conduction of the two cases is compared. In the first case, observed at the 22nd week, antenatal diagnosis of sirenomelia led to the therapeutic interruption of pregnancy. The second case, seen close to term, closed with the birth of an already dead sirenomelic foetus. PMID- 2193252 TI - [A case of fetal craniorachischisis. Early echographic diagnosis]. AB - The Authors point out the importance of ultrasonographic examination for the prenatal diagnosis of neural tube defects. They report a case of foetal craniorachischinosi, which was accidentally encountered, in the absence of clinical or anamnestic indications. They conclude that only the ultrasound method marker it possible to choose obstetric strategy when this anomaly is discovered early. PMID- 2193253 TI - [Duodenal atresia, dextrocardia, atrioventricular canal. Prenatal diagnosis and obstetric management]. AB - A case of fetal duodenal atresia, dextrocardia and common atrioventricular canal diagnosed by ultrasound is described. The Authors emphasize the evaluation of right criteria for the a probable transfer of pregnant women to a qualified specialistic institute. PMID- 2193254 TI - Beta-protein immunoreactivity in brains of patients with neuronal ceroid lipofuscinosis: ultrastructural and biochemical demonstration. AB - The storage pigment in neuronal ceroid lipofuscinoses (NCL) has a close similarity to age pigment lipofuscin. We studied immunoreactivity of isolated neuronal pigments from the juvenile form of NCL and aging control, using monoclonal antibodies (mAbs) against amyloid beta-protein. Ultrastructural localization of the immunoreactivity demonstrated that in NCL the epitopes are distributed mainly in curvilinear multilamellar arrays of the storage pigments and less in fingerprint profiles, while in aging control they are more homogeneously distributed on age pigment lipofuscin. The different distribution of the epitopes may reflect some catabolic as well as morphologic differences in lysosomes. A unique 31-kDa polypeptide detected on Western blots in NCL possibly derives from the same precursor, amyloid beta-protein precursor (ABPP). ABPP processing may be aberrant in NCL brains, and this can be detected as a 31-kDa polypeptide reactive with the mAbs. PMID- 2193255 TI - Calpain and calpastatin activity in the optic pathway. AB - The levels of the neutral proteolytic enzymes calpains and their endogenous inhibitor calpastatin were determined in the retina and in the retrobulbar optic pathway in the albino rabbit. The highest level of calpains was observed in the optic nerve with decreasing levels in the optic tract and superior colliculus. The level of calpastatin in the retina was very low compared to that in the optic nerve and tract and other parts of the nervous system. PMID- 2193257 TI - Baccalaureate and master's degree programs in nursing accredited by the NLN 1990 91. PMID- 2193256 TI - Endothelin-1 induces intracellular calcium rise and inositol 1,4,5-trisphosphate formation in cultured rat and human glioma cells. AB - The effects of endothelin-1 (ET) on the signal transduction in rat and human glioma cell line cells have been investigated. ET was found to initiate the increase of intracellular calcium ([Ca2+]i) levels in both C6 and A-172 cells, which was concurrent with the formation of inositol 1,4,5-trisphosphate (IP3(1,4,5)). In the presence of [ethylenebis(oxyethylenenitrilo)]tetraacetic acid (EGTA) in the incubation media, the duration of the intracellular calcium response was reduced, indicating that the ET-induced increase of intracellular calcium in glioma cells may be mediated by a dual mechanism, intracellular calcium mobilization and influx of extracellular calcium. These results suggest that ET may also act as a neuropeptide in the central nervous system. PMID- 2193258 TI - Recent advances in the chemistry and biochemistry of inositol phosphates of biological interest. PMID- 2193259 TI - The biosynthesis of C5-C20 terpenoid compounds. PMID- 2193260 TI - Natural sesquiterpenoids. PMID- 2193261 TI - Bacterial vaginosis: treatment with topical intravaginal clindamycin phosphate. AB - We tested topical intravaginal clindamycin phosphate at concentrations of 0.1, 1.0, and 2.0% in the treatment of 62 women with symptomatic bacterial vaginosis in a prospective, randomized, double-blind, placebo-controlled trial, and offered open-label treatment with 1.0% clindamycin to patients with persistent disease after blinded treatment. Blinded intravaginal clindamycin phosphate treatment cured bacterial vaginosis in 93.5% (43 of 46) of patients 4-7 days after therapy, compared with 25.0% (four of 16) of patients receiving placebo (P less than .001). One month later, 89.7% (35 of 39) of those who initially responded to clindamycin treatment showed persistent cure. There were no significant side effects. PMID- 2193262 TI - Antibiotic inhibition of bacterially induced fetal membrane weakening. AB - A fetal membrane model was used to evaluate in vitro the efficacy of two antibiotics, erythromycin and clindamycin, in preventing bacterial protease induced weakening of amniochorion. Standardized inocula of protease-producing bacteria (10(9) colony-forming units [cfu]/mL Staphylococcus aureus, incubated at 37C for 20 hours) reliably reduced fetal membrane structural integrity as reflected by bursting tension and work to rupture. Supraminimal inhibitory concentrations (supra-MICs) (erythromycin 0.23 microgram/mL; clindamycin 0.56 microgram/mL) and subminimal inhibitory concentrations (sub-MICs) (erythromycin 0.13 microgram/mL; clindamycin 0.06 microgram/mL) of both antibiotics prevented fetal membrane impairment due to test bacteria. Supra-MICs of both antibiotics prevented bacterial cell growth and release of protease. Sub-MICs of both antibiotics allowed bacterial cell growth of test microorganisms but inhibited protease release and subsequent fetal membrane damage. These findings suggest that inhibitory and even subinhibitory doses of antibiotics such as erythromycin and clindamycin may be effective in reducing the occurrence of premature rupture of membranes and subsequent preterm birth mediated by susceptible microorganisms. PMID- 2193263 TI - Updated screening protocol for abortion services. AB - We performed 2976 first-trimester abortions at our outpatient center in 1986. In 16 cases (0.54%), products of conception could not be confirmed histologically, although history, bimanual pelvic examination, and urine pregnancy test were suggestive of pregnancy. In 1987-1988, we prospectively evaluated 6689 women presenting for first-trimester abortions. Adding sonography and a semiquantitative serum hCG test to our earlier protocol, we were able to date and locate accurately 6510 pregnancies (97.3%) at the first visit. The remaining 179 patients (2.7%) required only one follow-up visit for final evaluation. This protocol reduced the number of visits for accurate evaluation of pregnancy and eliminated the risk of unnecessary curettage and unplanned second-trimester abortions. PMID- 2193264 TI - The safety of obstetric ultrasonography: concern for the fetus. AB - It has been estimated that more than half of all pregnant women in the United States undergo diagnostic ultrasound during their pregnancies. In light of this, the question of safety is of fundamental importance. Nondiagnostic ultrasound has been shown to produce biologic effects by thermal and cavitational activities. However, diagnostic ultrasound uses much lower intensities, and no evidence exists to suggest that it is associated with adverse effects. Numerous studies have examined the biologic effects of diagnostic ultrasound in insects, plants, cell suspensions, and even small mammals. The data from these experiments are confusing when attempting to relate these findings to the human. Epidemiologic data in humans, used to evaluate the potential adverse effects of exposure to diagnostic ultrasound, have revealed no ill effects from such exposure. Current data indicate that there are no confirmed biologic effects on patients and their fetuses from the use of diagnostic ultrasound and that the benefits to patients exposed to prudent use of diagnostic ultrasound outweigh the risks, if any. This review discusses the available information on the safety of obstetric ultrasonography. PMID- 2193265 TI - Acute pyelonephritis in pregnancy: a prospective study of oral versus intravenous antibiotic therapy. AB - Ninety pregnant women admitted to the high-risk pregnancy unit with a diagnosis of acute pyelonephritis were randomized to receive either oral (cephalexin 500 mg every 6 hours) or intravenous (IV) (cephalothin 1 g every 6 hours) antibiotic therapy. All patients were initially hydrated with 1 L of normal saline IV over 4 hours. Neither parenteral analgesics nor antiemetics were used. Bacteremia was noted in 13 (14.4%) of the 90 patients and mandated IV therapy. There was no difference between the oral and IV groups concerning predefined criteria for successful therapy (91.4 versus 92.9% successful therapy, respectively). No characteristic available at presentation predicted bacteremia or ultimate failure of therapy. Two patients (2.2%) experienced significant complications. These data suggest that in nonbacteremic patients, oral antibiotics are both safe and effective for the treatment of acute pyelonephritis in pregnancy. PMID- 2193266 TI - Uterine blood flow velocity waveforms in pregnant women during indomethacin therapy. AB - Continuous-wave Doppler ultrasound was used to assess blood flow velocities and determine the pulsatility index of the uterine arteries in ten pregnant women at 23-33 weeks' gestation during indomethacin therapy for preterm labor or polyhydramnios. There was no statistically significant difference in the pulsatility index of the uterine arteries during maternal indomethacin treatment (mean +/- SD 0.85 +/- 0.29) compared with pre-treatment values (0.85 +/- 0.23). Although studies in animals have reported that indomethacin increases uterine impedance to flow, it appears that it does not affect the uterine impedance in humans. PMID- 2193267 TI - Uterine and fetal flow velocity waveforms in hypertensive pregnancy: the effect of a single dose of nifedipine. AB - The short-term effect of 20 mg of oral nifedipine on maternal and fetal hemodynamics was investigated in 12 women with pregnancy-induced hypertension. Within an hour after nifedipine, the mean arterial blood pressure fell by 17% and there was a slight increase in maternal heart rate. There was also a decrease in the systolic/diastolic (S/D) ratio in the flow velocity waveform in the uterine artery in seven subjects, whereas the S/D ratio was unaffected in five subjects. Lack of change in the S/D ratio was associated with a less optimal pregnancy outcome: The neonates were delivered earlier, the rate of cesarean delivery was higher, and the newborns were smaller. No changes were observed in the fetal heart rate pattern or in the umbilical or middle cerebral artery flow velocity waveforms after nifedipine in hypertensive pregnancies. PMID- 2193268 TI - Doppler recordings of fetal movement: II. Comparison with maternal perception. AB - Twenty-seven women were studied to assess the relationship between maternally perceived fetal movement and that recorded by a Doppler device. Eighty-eight percent (433 of 492) of maternally perceived movements were detected by Doppler, but only 16% of movements detected by Doppler were maternally perceived (433 of 2196). When complex movements were classified by duration, those movements lasting between 20-60 seconds were most likely (correlation greater than 0.9) to be perceived by the mother. This Doppler method has the potential to replace maternal event marking and other techniques in the recording of fetal movement. PMID- 2193269 TI - Standardized measurement of amniotic fluid volume by correlation of sonography with dye dilution technique. AB - Amniotic fluid volume was measured in two ways in 23 subjects admitted for interruption of pregnancy at gestational ages 16-24 weeks. The amniotic fluid volume calculated from sonographic measurements was plotted against the "true" amniotic fluid volume obtained by a dye dilution technique. Linear regression analysis showed a good correlation between the two methods (r = 0.815; P less than .001) and yielded a factor that may be used on a general basis to derive the true amniotic fluid volume from the value obtained by sonography. This approach thus offers a standardized procedure for amniotic fluid volume estimation in the second trimester based on the technical simplicity of ultrasonography with the relative accuracy of the dye dilution technique. PMID- 2193270 TI - Early diagnosis of spina bifida: the value of cranial ultrasound markers. AB - Ultrasonography plays an integral part in the prenatal diagnosis of neural tube defects. However, experienced sonographers with careful evaluation are successful in accurately diagnosing spina bifida only 80-90% of the time. This study was conducted to evaluate the accuracy and reliability of certain cranial ultrasound markers--the "lemon sign," cerebellar abnormalities, microcephaly, and ventriculomegaly--in facilitating the diagnosis of spina bifida in patients referred for prenatal diagnosis. Open spina bifida was diagnosed in 24 of 44 fetuses found to have neural tube defects. The lemon sign and cerebellar abnormalities were identified in all 16 fetuses in whom the diagnosis of spina bifida was made between 16-24 weeks' gestation. In four of these fetuses, the lemon sign and cerebellar abnormalities were noted 1-2 weeks before the spinal defect was identified. Microcephaly was present in 69% and ventriculomegaly in 63% of the cases. In the eight cases diagnosed after 24 weeks' gestation, the lemon sign was less reliable, being noted in only 25% of the fetuses. Ventriculomegaly increased in frequency to 75% and cerebellar abnormalities and microcephaly were present in all. Our findings indicate that these cranial ultrasound markers are extremely reliable for the early diagnosis of spina bifida; their identification should alert ultrasonographers at all skill levels to the possibility of open spina bifida. PMID- 2193271 TI - Effect of cyclic estrone sulfate treatment on lipid profiles of postmenopausal women with elevated cholesterol levels. AB - The effects of two doses of cyclic unopposed estrone sulfate therapy on the lipid profiles of 153 healthy postmenopausal women with baseline total cholesterol levels above 219 mg/dL were compared in a multicenter, double-blind, placebo controlled study. Patients were assigned randomly to one of three treatment groups: estrone sulfate 0.625 mg (N = 59) or 1.25 mg (N = 43), or placebo (N = 51). The median baseline total cholesterol levels of the three treatment groups were 262, 269, and 262 mg/dL, respectively. Total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and the HDL/LDL ratio were assessed after 6, 9, and 12 months of treatment. There was a significant monotonic dose-response relationship of estrone sulfate in raising HDL levels, lowering LDL levels, and raising the HDL/LDL ratio at all intervals measured. These results indicate that estrone sulfate is effective in creating a beneficial change in the lipid profile of postmenopausal women with elevated baseline total cholesterol. PMID- 2193272 TI - The efficacy of presacral neurectomy for the relief of midline dysmenorrhea. AB - The present study was undertaken to evaluate prospectively the efficacy of presacral neurectomy for the treatment of midline dysmenorrhea. All patients had moderate to severe dysmenorrhea and stage III-IV endometriosis. Of the patients undergoing presacral neurectomy (N = 17), only two had a recurrence of pain. The remainder of the patients undergoing presacral neurectomy remain pain-free at 42 months of follow-up. Of the patients undergoing resection of endometriosis but not presacral neurectomy (N = 9), none received relief of midline pain. Relief of lateral pain, back pain, and dyspareunia was variable in both groups. Our findings corroborate previous retrospective studies showing that presacral neurectomy is highly effective in the treatment of dysmenorrhea. We speculate that the most common reasons for failure of presacral neurectomy are inappropriate selection of patients and incomplete resection of the presacral nerve plexus. PMID- 2193273 TI - Uterine activity compared with symptomatology in the detection of preterm labor. AB - The relative contribution of uterine activity obtained by home monitoring with a guard ring tocodynamometer compared with seven specific signs and symptoms reported during patient/nurse contact as an aid in detecting preterm labor has not been studied. In this prospective, multicenter study, patients at risk for developing early labor who were randomized to receive home uterine activity monitoring and perinatal nursing support were assessed. The initiator of provider contact (uterine activity detected on routine transmission, patient-perceived signs and symptoms of preterm labor during perinatal nurse contact, or both) resulting in a diagnosis of preterm labor was recorded. Contraction data were then analyzed for an association with preterm labor. There was a strong association of increased uterine activity (four or more contractions per hour) on a repeat monitoring strip with preterm labor (P less than .001). Among patients diagnosed with preterm labor, 31% had increased uterine activity detected on a routine transmission without patient-reported signs and symptoms, compared with 24% who were diagnosed as the result of patient-reported symptoms without increased uterine activity. Daily objective uterine activity data alone have greater incremental value over and above other signs and symptoms as an aid to the physician in diagnosing preterm labor. PMID- 2193274 TI - Prevention of preterm birth: clinical opinion. AB - Spontaneous preterm delivery continues to be the most significant problem facing clinicians as we enter the 1990s. Prevention of preterm labor still awaits needed improvements in prediction. At present, most preterm birth prevention programs are based upon the early recognition of preterm labor followed by prompt tocolysis. Programs based upon patient education and support, daily contact by trained nurses, intermittent cervical assessment, and daily sampling of uterine activity have been associated with a decrease in preterm birth. The exact contribution of each component to reduce preterm birth remains to be defined and, at present, a combination of the components is still suggested. PMID- 2193276 TI - Relationship of uterine contractility to preterm labor. AB - An increased uterine contraction rate is associated with preterm labor. The contraction rate in individual patients, however, has not been evaluated critically as to its predictive value in forecasting early labor. In this randomized multicenter study, 105 patients at high risk for preterm delivery monitored their contraction rate at home on a daily basis. An analysis was conducted to determine the association of at least four contractions per hour on a routine strip followed by at least four contractions per hour on a repeat tracing with subsequent preterm labor. Using this threshold, 70% of the patients were correctly classified. This contraction rate resulted in a sensitivity of 57%, a specificity of 80%, a positive predictive value of 72%, and a negative predictive value of 68%. A threshold rate of at least four contractions per hour on a remonitor strip identifies a patient at increased risk for preterm labor (P = .003). PMID- 2193275 TI - The contribution of symptomatology and/or uterine activity to the incidence of unscheduled visits. AB - Home uterine activity monitoring and perinatal nursing support have been shown to be associated with a decrease in preterm births with no increase in the number of unscheduled patient visits. This prospective, randomized multicenter study compared the frequency of unscheduled visits in patients receiving home uterine activity monitoring and perinatal nursing support with that of patients receiving education regarding the detection and reporting of preterm labor symptomatology. The contribution of patient-reported signs and symptoms versus objective uterine activity data to unscheduled visits is assessed. The overall frequency of unscheduled visits was similar in both groups. In the home uterine activity monitoring and perinatal nursing support group, the contributions of uterine activity versus signs and symptoms to the diagnosis of preterm labor were equal, with 36% of patients diagnosed with preterm labor sent to the physician for increased uterine activity and 36% for signs and symptoms. The sensitivity for the group receiving monitoring and nursing support in detecting preterm labor was 93%. The majority of false-positive visits were associated with patient symptoms. These data show that this combination service does not lead to a clinically significant increase in unscheduled visits. Further, the visits resulting from the combination service provide a sensitive predictive method to aid physicians in detecting early labor. PMID- 2193277 TI - Preterm birth: a puzzle worth solving. AB - The incidence of preterm birth has not declined in spite of obstetric and neonatal advances. Although results are variable, the majority of preterm birth prevention programs that embody risk assessment, patient education, and frequent provider visits have shown promise in reducing early births compared with those patients receiving standard care. More recently, home uterine activity monitoring has been shown to be accurate in demonstrating contraction frequency. The combination of this assessment method to detect increased uterine activity at the earliest possible time and intensive perinatal nursing support as to symptomatology related to preterm labor has led to an earlier detection of preterm labor. This, when combined with a comprehensive program of preterm birth prevention, has in many studies resulted in a decrease in the number of early deliveries. To achieve reduction in preterm births, however, these programs must be integrated with aggressive physician management of tocolytic therapy of such patients and continued intensive involvement in such gestations. PMID- 2193278 TI - Topical anaesthesia of the normal tympanic membrane: a controlled clinical trial of different suspensions of lidocaine. AB - The purpose of this investigation was to find an effective method for topical lidocaine anaesthesia of the tympanic membrane for minor therapeutical procedures. Twelve subjects with healthy ears were tested in a randomized double blind crossover trial. Xylocaine (lidocaine) aerosol 10%, lidocaine 4%, and lidocaine hydrochloride 5% were tested against placebo. Xylocaine aerosol was sprayed into a small container, shaken, and tempered. This made the application painless. The eardrum was stimulated by a point of a needle effective 25 min after application (p = 0.008 and p less than 0.05, respectively). Lidocaine hydrochloride showed no effect. No side effects were observed. The effectiveness seems to be dependent on the ionization of the drug, since the two effective drugs lidocaine and Xylocaine are un-ionized, whereas the ineffective lidocaine hydrochloride is ionized. PMID- 2193279 TI - [Correction of the position of the limbus in open reduction of congenital hip dislocation in children]. AB - On the basis of their clinical experience in the treatment of 146 patients with congenital dislocation of the hip the authors have evaluated the state of the limb in this pathologic condition. Various changes in the limb's form have been observed depending on the expression of the hip dislocation and on the patient's age. The instruments for incisions and for correcting the limb's position have been worked out. The fixation of the limb in the functionally correct position is carried out by stitching its fragments and fixing the strained threads in the greater trochanter area. The correction of the limb's position allows the subsequent correct development of the acetabular roof. PMID- 2193280 TI - [Experience with open reduction of congenital hip dislocation by the Ludloff method]. AB - The authors have performed simple open reduction of congenital dislocation of the hip after Ludloff in 54 children aged 3 months to 3 years. The total number of the operated joints was 79. The authors believe that this method provides favourable development of the acetabulum in the children operated before 1-2 years of age with the initial acetabular index below 30-40 degrees. In the children aged 2-3 years it should be regarded as one of the stages in the treatment of congenital dislocation of the hip. PMID- 2193281 TI - [Stages in the development of medical science at the Kiev Institute of Orthopedics]. PMID- 2193282 TI - [On the terminology of "congenital hip dislocation"]. PMID- 2193283 TI - [Hand holders: unification of the terminology]. PMID- 2193284 TI - [Diagnosis of chronic hematogenic osteomyelitis (review of the literature)]. PMID- 2193285 TI - [Intra- and postoperative complications of arthroscopic surgery of the knee joint]. AB - In a review of the literature, intra- and postoperative complications in arthroscopic surgery of the knee joint are analyzed on the basis of 167,210 reported cases. Depending on the variable criteria and definitions, the respective studies are based upon the individual complication rates differ greatly between 0.8 and 17.7%. The incidence of serious complications was less than 1%. Factor analysis proved the following variables to be correlated with the incidence of complications: age and sex, kind and etiology of joint lesion, kind of operative procedure performed, duration of operation, and experience of the surgeon. Compared to arthrotomy, arthroscopic surgery is associated with reduced morbidity and a low complication rate. PMID- 2193286 TI - [Instrumental and technical prerequisites for arthroscopic surgery of the knee joint]. AB - The continuous improvement of intrumentation and equipment is the reason for the steady increase in arthroscopic operations. As the technical equipment is becoming increasingly complicated, attention must be paid to training and standardized procedures in order to ensure that the arthroscopic operative procedure is fast, safe, and without complications. Special operative techniques and instruments have been approved for clinical use, depending on the arthroscopic operation. PMID- 2193287 TI - [Arthroscopic surgery: meniscus refixation and meniscus healing]. AB - The stabilizing function of the meniscus and the negative effect of a complete or partial meniscectomy have been demonstrated in many studies. On the other hand, it has also been shown that meniscus tears in certain locations can heal very well. The prerequisite is that the torn meniscus can be revascularized from the capsule. Revascularization can be achieved by stimulating the formation of new vessels, but also by the build-up of collagen after induction of fibrochondrocytes and fibroblasts. The requirements for meniscus reconstruction are: careful preparation of the tear, exact repositioning, and precise placement of the sutures. The additional activation of regenerating processes is promoted by using a fibrin clot. In this study, 54 patients underwent meniscus repair, but the results in this group that also received a fibrin clot are not included. In the case of longitudinal-vertical tears of the meniscus inside the 3-mm zone margin, it was decided that the procedure was indicated when tears longer than 1.5 cm were concerned. The inside-out technique was used. Subjective and objective examination of 52 patients showed that the clinical results were good to very good in 92%. PMID- 2193288 TI - [The "patellofemoral joint" problem]. AB - In the differential diagnosis of femoropatellar joint disease, three conditions must be considered: (1) peripatellar irritation; (2) chondromalacia of the patella; (3) femoropatellar arthrosis. In approximately 90% of the cases, peripatellar irritation and chondromalacia of the patella can be kept under control by active extension and strengthening exercises for the femoral flexor and extensor musculature. In therapy-resistant cases, arthroscopic surgery can provide the opportunity to influence the pathological gliding process positively. The operative procedure is planned on the basis of clinical and radiological examinations and computed tomography investigations. Dysplasia of the patella, including a lax patella, not only requires lateral release, but also medial tightening whereas patellar insufficiency can be treated successfully by lateral release alone. In our new staging procedure, chondromalacia and femoropatellar arthrosis are differentiated. Stage III chondromalacia is simply smoothed out via arthroscopy. In the treatment of femoropatellar arthrosis, on the other hand, restitution of the cartilage defect is of most importance. The age of the patient and staging of the cartilage defect determine which therapeutic procedure is to be used. The "release" operations in the treatment of femoropatellar arthrosis serve to relieve the damaged cartilage area and depend on the axial positioning of the knee joint. PMID- 2193289 TI - [Arthroscopic cruciate ligament reinsertion and augmentation. Indications- surgical technic]. AB - The advantages of arthroscopic refixation and augmentation of the cruciate ligament in comparison to open methods are conserving innervation of the most important structures of the knee joint, a clear-cut reduction in morbidity, and more rapid rehabilitation of the knee joint. In principle, however, as far as ligament replacement and fixation of the augmented ligament parts are concerned, the technique corresponds to the open method. As the early results refer to a period of 2 years at most, however, it is too soon to report them. Nevertheless, the results of follow-up in our present study are identical to those previously reported by other authors. PMID- 2193290 TI - Transcription elongation and eukaryotic gene regulation. AB - Each step in the synthesis of functional transcript by RNA polymerase II provides a level at which gene expression can be regulated. Control over the elongation phase of transcription is a recognized regulatory mechanism in prokaryotes; however, only recently have examples of conditional transcription elongation blockage been reported in eukaryotic cellular genes. In several cases, control over transcription elongation clearly contributes to the regulated expression of these genes. Indeed, reports that transcription by RNA polymerase II is initiated and paused on many Drosophila promoters, prior to induction of gene expression, suggests that release of an arrested polymerase, as opposed to polymerase recruitment to a disengaged promoter, may be the key regulatory step for many genes thought to be controlled by transcription initiation (Rougvie & Lis, 1988). RNA polymerase II undergoes modifications, such as association with ancillary elongation factors and phosphorylation of its large subunit carboxy terminal domain (CTD), at stages subsequent to recruitment to a promoter and establishment of a pre-initiation complex (Reinberg & Roeder, 1987; Rappaport et al., 1987; Payne et al., 1989; Laybourn & Dahmus, 1989). It is possible that modifications such as these, or others occurring prior to, during or following transcription initiation, may alter the holoenzyme's transcription elongation properties, to allow recognition or read-through of elongation block signals within a transcription unit. In this review, we will present features of transcription elongation blockage in several eukaryotic cellular genes in the context of our understanding of attenuation and premature transcription termination in prokaryotic and viral genes. We will also present evidence supporting the model that modifications to the RNA polymerase II transcription complex are pivotal to the control of transcriptional at the level of elongation. PMID- 2193291 TI - Structure, chromosome mapping and expression of the murine Fgf-6 gene. AB - The sixth member of the fibroblast growth factor gene family was cloned and analysed in the mouse. It is composed of three coding exons and encodes a putative growth protein of 198 amino acids, possessing a potential signal peptide, and presenting 79% and 93.5% sequence similarity with the mouse Hst/K fgf and human FGF-6 genes products, respectively. The murine Fgf-6 gene is located in a region distinct from the Int-41 locus and belongs to a linkage group conserved between chromosome 12 in man and chromosome 6 in mouse. It presents an intrinsic oncogenic capacity since it is able to transform cultured fibroblasts. Fgf-6 mRNA levels are developmentally regulated with a peak of expression in the developing fetus at day 15.5 of gestation, moderate levels during late gestation and in the neonate. In the adult, Fgf-6 mRNA can be detected in testis, heart and skeletal muscle. PMID- 2193292 TI - Tumour-related expression of a translation-elongation factor-like protein. AB - We have identified a tumour-related 43 kd cytoplasmic protein (LC/p43) using a monoclonal antibody against the total proteins of human hepatoma cell line PLC/PRF/5. LC/p43 is preferentially expressed in a variety of tumours of human and animal origin, whereas no expression was detected in several normal adult tissues tested. LC/p43 expression was induced in rodent fibroblasts upon transfection with several viral oncogenes. Expression in non-transformed peripheral blood lymphocytes could be induced by treatment with phytohaemagglutinin (PHA) and subsequent culture with interleukin II, whereas retinoic acid treatment of transformed cells caused a drastic reduction of the antigen in the cells. Sequence analysis of three tryptic peptides of LC/p43 revealed 50-70% homology to different domains of the eukaryotic and prokaryotic translation-elongation factors EF1-alpha and EF-Tu, respectively. PMID- 2193293 TI - Efficient induction of focus formation in a subclone of NIH3T3 cells by c-myc and its inhibition by serum and by growth factors. AB - In both experimental and spontaneous tumors, c-myc expression is often enhanced following its amplification or its rearrangement adjacent to a strong promotor/enhancer. However, c-myc by itself does not induce foci efficiently in fibroblast cultures. The effect of high levels of c-myc expression from a retroviral construct was investigated in several rodent fibroblast cell lines grown in medium containing 10% fetal calf serum or in serum-free PC-1 medium. c myc-infected NIH3T3 clone 7 cells exhibited efficient quantitative focus formation when grown in PC-1 medium, whereas foci were not detected when grown in serum-supplemented medium. NIH3T3 clone 7 was the only cell line found to be sensitive to c-myc; other clones of NIH3T3 or other rodent fibroblast cell lines proved to be resistant to c-myc focus formation. At least two major types of morphologically distinct c-myc-induced foci were observed; the first was similar to ras-transformed foci induced in NIH3T3 and other fibroblast cell lines, and the second type was composed of adipocyte-like cells similar to NIH3T3 L1 cells. The c-myc infected cells cloned from these two types of foci expressed high levels of retrovirus-derived c-myc RNA and exhibited elevated levels of immunoreactive myc protein, as detected by immunofluorescent staining with an anti-myc polyclonal antibody. c-myc-transformed clones displayed only a limited ability to grow in soft-agar in the presence of serum and were not tumorigenic in nude mice. Focus formation by c-myc was quantitatively inhibited by the addition of interferon alpha + beta (INF alpha, beta), tumor necrosis factor alpha (TNF alpha) or transforming growth factor beta 1 (TGF beta 1) to the serum-free PC-1 medium, and, in correlation, NIH3T3 clone 7 cells produced the lowest level of endogenous TGF beta of the various cell lines tested. PMID- 2193295 TI - Children's drawings as a projective technique. AB - Body image is the constantly changing mental picture of one's body. The examination of children's drawings provides an insight into cognitive and psychosocial functioning, which are important aspects in their development of self-concept. PMID- 2193294 TI - Amplification of the int-2 gene in human head and neck squamous cell carcinomas. AB - Head and neck squamous cell carcinomas (SCC) from 21 patients were analyzed for structurally rearranged or amplified proto-oncogenes by Southern blot hybridization. The int-2 proto-oncogene was amplified 3-5 fold in 5 (50%) of 10 laryngeal SCC and 2-3 fold in 5 (45%) of 11 nonlaryngeal SCC of the head and neck. Adjacent histologically normal tissue from the same patients had single int 2 gene copy number. Coamplification of int-2 and the epidermal growth factor receptor (c-erbB-1) gene was found in one laryngeal SCC and one SCC metastatic to the neck. No amplification or structural alterations of proto-oncogenes c-erbB 2/HER2, c-myc, H-ras-1, or K-ras-2 was detected in any of the head and neck tumors. In a survey of head and neck tumor-derived cell lines, int-2 was amplified 9 fold in a hypopharyngeal tumor cell line (FaDu), but not amplified in 3 laryngeal tumor cell lines. int-2 has been localized to the q13 band of chromosome 11. We used chromosome 11 specific probes to demonstrate that int-2 amplification was not due to complete or partial chromosome 11 duplication. int-2 amplification was localized to 11q13, but did not extend to the ets-1 locus 11q23. The results indicate that int-2 is frequently amplified in SCC of the head and neck and suggest that int-2 amplification may correlate with clinical disease progression. PMID- 2193296 TI - Childhood cancer: siblings draw and tell. AB - There is a growing awareness among health care professionals that the psychosocial needs of siblings of children with cancer are less adequately met than those of other family members. As part of a larger research study of 17 families of children with cancer, 20 healthy siblings, ages 3-11 years (7 males, 13 females), were tested using the Kinetic Family Drawing-Revised (Spinetta, McLaren, Fox, & Sparta, 1981) in one of two oncology clinics in a Southwestern state. Nine of the subjects participated in a sibling day. Data from the drawings and discussions with siblings confirm previous sibling research findings and reflect current social changes. PMID- 2193297 TI - Teaching children about their internal bodies. AB - Children's knowledge about their internal bodies is related to their developmental age and the manner in which they are taught. Nurses need to consider appropriate methods, language, and timing for teaching basic anatomy and physiology to early school-age children to increase its effectiveness. PMID- 2193298 TI - Childhood cancers: incidence, etiology, diagnosis, and treatment. AB - Treatment advances over the last few decades have dramatically increased survival for children with cancer. More than half the children treated for cancer are now cured. Consequently, professionals working with these children are beginning to focus on minimizing the adverse effects of cancer and its treatment as well as helping families cope with a chronic, life-threatening illness. This article presents an overview of the incidence, etiology, diagnosis, and treatment of common childhood cancers. Approaches to care, efforts to prevent acute and late toxic effects, and nursing management of children with malignancies are discussed. PMID- 2193299 TI - Diagnosis of human immunodeficiency virus infection in infants and children. PMID- 2193300 TI - Can home visitation improve the health of women and children at environmental risk? AB - We reviewed randomized trials of prenatal and infancy home-visitation programs for socially disadvantaged women and children. Some home-visitation programs were effective in improving women's health-related behaviors during pregnancy, the birth weight and length of gestation of babies born to smokers and young adolescents, parents' interaction with their children, and children's developmental status; reducing the incidence of child abuse and neglect, childhood behavioral problems, emergency department visits and hospitalizations for injury, and unintended subsequent pregnancies; and increasing mothers' participation in the work force. The more effective programs employed nurses who began visiting during pregnancy, who visited frequently and long enough to establish a therapeutic alliance with families, and who addressed the systems of behavioral and psychosocial factors that influence maternal and child outcomes. They also targeted families at greater risk for health problems by virtue of the parents' poverty and lack of personal and social resources. PMID- 2193301 TI - American Academy of Pediatrics Committee on Infectious Diseases: Dexamethasone therapy for bacterial meningitis in infants and children. PMID- 2193302 TI - Ultrasonographic studies in the management of recurrent abdominal pain. AB - The medical records of 65 children and adolescents who had abdominal ultrasonography for the evaluation of recurrent abdominal pain were reviewed. Fifty-three subjects (81%) had normal results; in 12 cases (19%) an abnormality was detected. In no case could the pain be attributed to the abnormal finding. Furthermore, in 3 subjects, disclosure of the abnormal findings could have caused more harm than good. The role of the abdominal ultrasonographic study in the management of recurrent abdominal pain in children and adolescents is discussed. PMID- 2193303 TI - Psychological development of children who were treated antenatally with corticosteroids to prevent respiratory distress syndrome. AB - Potential side effects of antenatal administration of corticosteroids to prevent neonatal respiratory distress syndrome were studied in 10- to 12-year-old children whose mothers had participated in a randomized, double-blind, placebo controlled trial of betamethasone. Aspects of the children's intellectual and motor development, school achievement, and social-emotional functioning were investigated. There were no differences between the corticoid group and the placebo group on these variables, nor were there more children with learning difficulties and behavioral disturbances in either of the groups. PMID- 2193304 TI - Physical development and medical history of children who were treated antenatally with corticosteroids to prevent respiratory distress syndrome: a 10- to 12-year follow-up. AB - Potential side effects of antenatal administration of corticosteroids to prevent neonatal respiratory distress syndrome were studied in 10- to 12-year-old children whose mothers had participated in a randomized, double-blind, placebo controlled trial of betamethasone. The children had a general physical examination; parents were interviewed about the medical history of their child with special attention to infectious diseases; growth data were collected; and a developmental neurological examination, an ophthalmological examination, and a lung function test were conducted. In the corticosteroid group significantly more hospital admissions because of infectious diseases during the first years of life were reported. On the other variables no differences between the corticoid and the placebo groups were found. PMID- 2193305 TI - Epidermolysis bullosa dystrophica inversa in a child. AB - A 4-year-old child with dystrophic epidermolysis bullosa inversa is described. Clinical features were blistering of the skin, erosions, scarring and milia formation. The areas involved included the trunk, with preference for the axillary and inguinal folds, the neck and sacral area, and proximal extremities. Notably, the hands and feet were completely spared, with only mild nail dystrophy. Ultrastructural analysis revealed dermolytic blistering and absent or rudimentary anchoring fibrils. Collagen VII, the main structural protein of these fibrils, was present in the skin, as shown by indirect immunofluorescence. These findings suggest that a mutation that prevents appropriate supramolecular aggregation of collagen VII into anchoring fibrils may underlie this subtype of dystrophic epidermolysis bullosa in some patients. PMID- 2193306 TI - Feasibility of a randomized trial of a low-fat diet for the prevention of breast cancer: dietary compliance in the Women's Health Trial Vanguard Study. AB - The Women's Health Trial Vanguard Study was conducted to examine the feasibility of a nationwide, randomized multicenter intervention trial to test the hypothesis that a low-fat diet followed for a period of 10 years will reduce breast cancer risk. Women ages 45-69 years at increased risk of breast cancer were randomized into intervention (low-fat diet, n = 184) and control (usual diet, n = 119) groups. On the basis of 4-day food records, baseline fat intakes were comparable in the two groups, averaging 1,718 kcal with 39% of energy as fat. Intervention women reported substantially lower fat intake at 6 (20.9% kcal), 12 (21.6%), and 24 months (22.6% kcal). In contrast, control women reported only slight reductions in fat intake (37.3% kcal at 12 months and 36.8% kcal at 24 months). Evidence that these women were indeed complying with the low-fat dietary intervention comes from (a) the reasonable nature of reported nutrient changes within food groups in the intervention women and (b) agreement between observed and expected differences in plasma total cholesterol between the control and the intervention groups. At 12 months, the observed control - intervention plasma cholesterol difference was 13.1 +/- 4.6 mg/dl while the expected difference based on the Keys equation was 15.1 +/- 1.1 mg/dl; at 24 months, the observed difference was 15.5 +/- 4.3 mg/dl and the expected difference was 12.0 +/- 1.2 mg/dl. These analyses indicate that the intervention women made substantial dietary changes and have successfully maintained these changes over a 2-year period. This study thus demonstrates the feasibility of a randomized trial with an intensive low-fat dietary intervention. PMID- 2193307 TI - Cigarette smoking behavior is strongly related to educational status: the CARDIA study. AB - The prevalence and correlates of cigarette smoking were examined in 5,116 men and women ages 18-30 years including both blacks and whites of varied educational levels. Prevalence of smoking was approximately 30% in each race by gender subgroup after adjusting for age and education. The prevalence decreased with increasing education, from 54% among participants with less than a high school education to 12% among those with graduate degrees (P less than 0.001). Cessation rates followed a similar pattern, with former smokers twice as common among those with more education. Differences in smoking prevalence across occupational groups were largely explained by differences in educational achievement. More educated individuals smoked fewer cigarettes per day and chose brands with lower nicotine yield. Race and gender were not strongly related to smoking prevalence. However, among smokers, whites reported smoking 50% more cigarettes per day than blacks but the average nicotine and tar content of the cigarette was nearly three times higher among blacks than whites. The strong inverse relationship between education and cigarette smoking patterns has important implications for public health efforts directed at the prevention of cigarette smoking. PMID- 2193309 TI - [Infections of the airways--when are antibiotics indicated?]. PMID- 2193308 TI - A review of the use of saliva cotinine as a marker of tobacco smoke exposure. AB - Cotinine, the major metabolite of nicotine, is a useful marker of exposure to tobacco smoke. It can be measured in plasma, urine, or saliva. However, distinguishing between active and passive smoking on the basis of a cotinine measurement may be difficult. In order to evaluate the relationship between saliva cotinine concentration and self-reported tobacco smoke exposure in both active and passive smokers, an English-language literature search using MEDLINE was conducted (1973-1989), and the bibliographies of identified articles were reviewed. Of 43 originally identified articles, only 22 met the criteria for inclusion. Specific information regarding population studied, reported tobacco smoke exposure, method of measurement, and cotinine concentrations was assessed. Passive smokers usually have cotinine concentrations in saliva below 5 ng/ml, but heavy passive exposure can result in levels greater than or equal to 10 ng/ml. Levels between 10 and 100 ng/ml may result from infrequent active smoking or regular active smoking with low nicotine intake. Levels greater than 100 ng/ml are probably the result of regular active smoking. Four categorizations of tobacco smoke exposure are suggested on the basis of saliva cotinine concentrations. PMID- 2193310 TI - Participation of the CNS in the control of FFA mobilization during fasting in rabbits. AB - The presence of FFA-mobilizing areas in the rabbit central nervous system was investigated by injecting minute amounts of 2-deoxyglucose, glucose or insulin directly into the cerebrospinal fluid of conscious, unrestrained rabbits. Intracerebroventricular administration of minute amounts (10 mg) of deoxyglucose to fed rabbits produced a rapid increase in the concentration of plasma free fatty acids (FFA) and a slower increase in plasma glucose. Conversely, small amounts of insulin (50 microU) or glucose (2.5 mg) intraventricularly reduced the elevated plasma FFA of normal fasted rabbits without affecting plasma levels of glucose or insulin. The elevated levels of plasma FFA of diabetic rabbits were not affected by glucose administration, but clearly decreased after intraventricular insulin. Adrenodemedullation suppressed the hyperglycemia but not the plasma FFA increase induced by intraventricular 2-deoxyglucose. The data suggest that insulin-sensitive centers in the rabbit central nervous system participate in the control of FFA mobilization during fasting by modulating the lipolytic sympathetic tonus of adipose tissue, and that the activity of these centers is regulated by their rate of glucose utilization. PMID- 2193311 TI - Sexual performance of old and young male rhesus macaques following treatment with GnRH. AB - GnRH has been reported to facilitate sexual performance in a number of species. To determine whether the same was true for rhesus monkeys we measured sexual behavior and serum levels of testosterone (T) and luteinizing hormone (LH) following control tests and after treatment with two doses of GnRH. In the first experiment, old intact (N = 11) and old T-implanted, castrated (N = 4) rhesus macaques were examined. Mean intromission rate of old intact males was significantly lower following treatment with 100 micrograms of GnRH than following control injections. Other measures of sexual behavior did not differ across treatments. There were no significant treatment effects among the old castrated males. The failure to facilitate sexual performance may have been due to the age of the males and not to the species under study. Thus, in a second experiment the effects of GnRH were examined in young rhesus males. Again, there was no facilitation of sexual performance. This cannot be accounted for by a failure of GnRH to produce a physiological response. For both old and young intact males serum levels of LH and T increased significantly after treatment with both doses of GnRH. LH but not T levels increased significantly in the T implanted males. PMID- 2193312 TI - Cutaneous odontogenic sinus simulating a basal cell carcinoma: case report and literature review. AB - A woman was referred for Mohs' microscopically controlled surgical excision of a presumptive basal cell carcinoma located on her nasolabial fold. During examination, pus was expressed from the nodulocystic lesion and an intraoral palpation revealed a fibrous sinus tract extending from the skin lesion to the gingiva of a severely carious tooth. There was roentgenographic evidence of a periapical abscess. The diagnosis was revised to that of a cutaneous odontogenic sinus. The possibility of a draining dental sinus to the skin should be seriously considered when evaluating a suspected basal cell carcinoma in the perioral region--especially in an individual with a history of extensive dental treatments, antecedent oral trauma, or markedly carious teeth. PMID- 2193313 TI - Federigo da Montrafeltro. PMID- 2193314 TI - Whither self-governing hospital trusts? A look back to the North Bierley Union 1848-61. PMID- 2193316 TI - The neurochemistry of mania: a hypothesis of etiology and rationale for treatment. AB - 1. The author delineates the emergence of an important concept in the Neurochemistry of mental illness, that of a Cholinergic Factor in Mania. This concept which evolved steadily over a period of 22 years from 1950-1972, the author believes has given us our first significant insight into the etiology and treatment of the Manic state. 2. In addition, the author examines the Adrenergic Cholinergic hypothesis of Mania and Depression and the Brain Cholinergic Adrenergic Balance hypothesis for Mania and Schizophrenia. 3. Also described in this article are some successful preliminary attempts by others, to treat Mania with Phosphatidyl Choline and the author will present, for the first time, data relating to success with the use of Phosphatidyl Choline in bringing about permanent remission of mania in 10 treatment subjects since 1983. 4. In conclusion the author proposes a Cholinergic Insufficiency Hypothesis as a primary factor in the causation of Mania and comments on a presumptive role in the modulation and balance of Adrenergic Dominance by Presynaptic Receptors positioned on the Nerve Terminals of Adrenergic Neurons. PMID- 2193315 TI - Measurement of plasma homovanillic acid concentrations in schizophrenic patients. AB - 1. Several lines of evidence suggest that abnormalities of central dopaminergic transmission may be involved in the expression of some schizophrenic symptoms. However, elucidation of the role of dopamine (DA) in schizophrenia has eluded investigative efforts partially because no accurate and easily repeatable measure of brain DA activity exists. 2. The development of a technique to measure homovanillic acid in plasma has offered the possibility of performing serial measurements of this major DA metabolite. 3. Assuming that plasma homovanillic acid (PHVA) concentrations is an index of brain DA activity, measurement of PHVA can play a role in elucidating the DA abnormality in schizophrenia. 4. Results to date suggest that plasma homovanillic acid concentrations are lower in chronic schizophrenic patients compared to normal controls, and that PHVA values correlate with schizophrenic symptom severity. 5. In addition, PHVA levels were shown to initially rise and subsequently decline during chronic neuroleptic administration in treatment responsive but not in treatment refractory schizophrenic patients. PMID- 2193317 TI - [Karl Kraus and psychoanalysis. A historical documentary study]. AB - Through numerous quotations from Karl Kraus's journal Die Fackel the author points out that the traditional psychoanalytic picture (as transmitted by Jones) of Karl Kraus as one of Freud's fiercest adversaries is to be reconsidered. PMID- 2193318 TI - Tumour shrinkage and down staging after preoperative radiation of rectal adenocarcinomas. AB - In order to analyse the influence of low radiation doses on human rectal adenocarcinomas, gross and microscopical changes after preoperative radiation were compared to controls treated with immediate surgery in a randomised, prospective trial. The X-ray doses given were 31.5 Gy in 3.5 weeks, and the interval between radiation and operation was 2 to 3 weeks. A total of 138 patients having preoperative radiotherapy and 131 controls were analysed. The overall tumour size was reduced after radiation. Complete tumour regression was obtained in six (4.4%) patients. All of these tumours were exophytic and mobile at the initial examination and all were either well or moderately well differentiated. A significant downstaging was found after preoperative radiation. The incidence of positive lymph nodes was 27.5% in the resected specimens in controls and 18.4% after radiation (p less than 0.05). The total number of recurrences was reduced after radiation in stage C2 tumours, but not in the other stages. Preoperative radiation did not influence the histological grade of the tumours. There was no difference between the two randomised groups with respect to 5-year survival or disease-free survival in any histopathological stage. PMID- 2193319 TI - Irradiation for xenogeneic transplantation. AB - Xenogeneic transplantation (XT) is the transplantation of organs or tissues from a member of one species to a member of another. Mammalian species frequently have circulating antibody which is directed against the foreign organ irrespective of known prior antigen exposure. This antibody may lead to hyperacute rejection. There is no reliable means to avert hyperacute rejection once it ensues so efforts must be directed towards eliminating the pre-existing antibody. In those species in which hyperacute rejection of xenografts does not occur, cell-mediated rejection, similar to allograft rejection, may occur. It is in the prevention of this latter form of rejection that radiation is most likely to be beneficial in XT. Both total lymphoid irradiation (TLI) and selective lymphoid irradiation (SLI) have been investigated for use in conjunction with XT. TLI has contributed to the prolongation of pancreatic islet-cell xenografts from hamsters to rats. TLI has also markedly prolonged the survival of cardiac transplants from hamsters to rats. A more modest prolongation of graft survival has been seen with the use of TLI in rabbit-to-rat exchanges. Therapy with TLI, cyclosporine, and splenectomy has markedly prolonged the survival of liver transplants from hamsters to rats, and preliminary data suggest that TLI may contribute to the prolongation of graft survival in the transplantation of hearts from monkeys to baboons. SLI appears to have prolonged graft survival, when used in conjunction with anti-lymphocyte globulin, in hamster-to-rat cardiac graft exchanges. The current state of knowledge of the use of irradiation in experimental XT is reviewed. PMID- 2193320 TI - [Radiourology]. PMID- 2193321 TI - [The diagnostic potentials of echography in thoracic pathology]. PMID- 2193322 TI - [The seriatim echographic assessment of the volume of hepatic metastases]. AB - The quantitative study of neoplastic growth patterns is the ground for a correct clinical approach to patients with malignant tumors, for both prognosis and evaluation of treatment outcome. The growth of 19 hepatic metastases in 13 patients was therefore followed; the lesions diameters were measured by means of US and their volumes were calculated. The results were plotted in semilogarithmic scale and doubling times (DT) were calculated. The DT values observed were ordered according to the origin of the tumors and to their growth rate; our values were in substantial agreement with literature data. Moreover, the differential increase in the metastases diameters along the 3 orthogonal planes was analysed and a significant rate of asymmetrical growth was shown. Changes in the echo structure of the observed metastases were evaluated and the changes in peripheral hypoechoic halo were demonstrated. The authors stress the importance of a correct volumetric study during US follow-up of patients with hepatic metastases. PMID- 2193323 TI - [The prevalence of diffuse and focal lesions of the hepatic parenchyma in a nonselected, resident population. A prospective echographic study]. AB - A group of 2978 randomly chosen residents from a rural area of Veneto (Italian region), aged 18-69 years, was assumed as a study population. They underwent US examination of the liver, routine liver function tests, and--when necessary- other imaging techniques and liver biopsy. Liver US exam detected diffuse lesions in 26% of cases (mostly bright liver pattern), and focal lesions in 3%; US findings were normal in 66% of patients and questionable or inconclusive in 5%. As far as focal lesions were concerned, the final diagnosis was angioma (24 cases), cyst (31), neoplasm (5). When bright liver pattern was observed, liver function tests were altered in 78% of the patients; when US findings were normal, liver function tests were normal in 59% of cases. In conclusion our data: 1) show that focal and diffuse liver abnormalities are relatively frequent in unselected and asymptomatic people, 2) confirm US diagnostic utility, and 3) suggest that US be employed as a screening exam in study populations. PMID- 2193324 TI - [Echography in the follow-up of neonatal adrenal hemorrhage. The presentation of 14 cases]. AB - Fourteen cases are reported of monolateral adrenal hemorrhage in newborns who were submitted to US exam at 1 week, 2 weeks, 3 weeks, and 3 months of age. The variability is emphasized of US and pathologic findings according to the patients' age. A concise terminology is suggested allowing the description of morphological and echo-structural patterns in adrenal hemorrhage. Being familiar with US spectrum of neonatal adrenal hemorrhage appearances can provide useful data in the cases with atypical clinical features. Moreover, the differential diagnosis becomes easier of neonatal adrenal hemorrhage and other diseases such as neonatal neuroblastoma, adrenal abscess, cystic neuroblastoma, cortical renal cyst, and obstructed upper cortical renal cyst, and obstructed upper excretory tract in duplicated kidney. The most effective criterion for US differential diagnosis is probably the chronological variability of US findings. Sonography is stressed as an useful and effective imaging modality in the diagnosis and follow up of adrenal hemorrhage which helps avoid X-ray investigations and unnecessary laparotomies. PMID- 2193325 TI - [The predictability of the radiotherapy response in epidermoid tumors of the head and neck. A review of the literature and mathematical models for choosing the fractionated doses]. AB - Literature data show that the term "squamous-cell head and neck cancer" includes a wide range of epidermoid cell subgroups, each of them with its own intrinsic radiosensitivity (Do values ranging from 107 to 184 in primary tumors, and 146 263 in recurrences; n values ranging from 1 to 5; and, if we consider linear quadratic model alpha values from 0.273 to 0.490 and beta values from 0.029 0.045). Different sublethal and potential lethal repair times are also observed (4-6 hours and 12-24 hours, respectively), and structural tissue heterogeneity (hypoxic fraction oscillating 5%-30% of the neoplasm). Most important, different kinetic parameters are demonstrated, with Labelling Index ranging from 4% to 30%, phase-S time from 6 to 19 hours, and potential doubling time from 2 to 20 days. On the basis of Fowler's and Barendsen's mathematical models and knowing the potential doubling time and Labelling Index values (derived from bioptic specimens), as well as alpha/beta ratio for both tumor and normal tissue, we tried to identify the optimal fractionation (standard, accelerated, hyperfractionated) for slow/fast-growth tumors, also evaluating the relative acute and late side effects. Our analysis shows that: 1) tumors with aggressive biological behavior (Labelling Index greater than 15%, aneuploidy, potential doubling time less than 5 days) seem to respond to accelerated fractionation/hyperfractionation without split better than to standard regimens: 2) tumors with slow growth (Labelling Index less than 15%, potential doubling time greater than 5 days, euploidy) seem to respond not only to standard regimens, but also--and mainly--to hyperfractionation. PMID- 2193326 TI - [A case of the rupture of an inflammatory aneurysm of the aortic arch]. PMID- 2193327 TI - [Metastases of the skeletal muscles. The echographic aspects]. PMID- 2193328 TI - [Generalized hemorrhagic diathesis and anemia of sudden onset caused by rhabdomyolysis diagnosed as acute leukosis]. AB - A case of severe acute rhabdomyolysis (RML) is reported which was caused by marked hypokalemia associated with long-lasting diarrhea. Since the patient not only had severe muscular symptoms but also intense hemorrhagic diathesis and anemia, the first diagnosis on admission was acute leukemia. Due to the increasing occurrence of acute RML associated with different clinical conditions, including hematologic disorders, the hematologist should keep in mind the possibility of RML, both as a primitive disorder or complication, and require CPK and myoglobin assay routinely. PMID- 2193329 TI - [The physician between the patient and the medical equipment]. PMID- 2193330 TI - Giant cell (temporal) arteritis-polymyalgia rheumatica: a critical review. AB - Giant cell (temporal) arteritis G.C.(T) A. is common disorder and affects medium sized and large arteries in people over the age of fifty. Many series show that up to 50% of people with the clinical syndrome of polymyalgia rheumatica (PMR) go on to develop manifestations of G.C.(T) A. within a year; others may do so later. A critical review is offered of aspects of the subject which despite much study and research remain controversial or neglected. This includes epidemiology: statistics from routine autopsy suggests that the disease affects more people than are diagnosed clinically. The need to resolve uncertainty whether intracerebral vessels are involved or not, is now urgent, particularly in view of the wide spread use of short courses of Dexamethasone in the treatment of stroke. All clinicians should recognise the implications of the fact that they are dealing with a disease which may be active and yet symptomatically silent. PMID- 2193331 TI - Sequestration of N-acetyl-beta-D-glucosaminidase in somatic cells during experimental bovine mastitis induced by endotoxin, Staphylococcus aureus or Streptococcus agalactiae. AB - Experimental mastitis was induced in cows by intramammary infusion of endotoxin, Staphylococcus aureus or Streptococcus agalactiae. The inflammatory response was monitored by somatic cell counting and N-acetyl-beta-D-glucosaminidase (NAGase). NAGase activity was analysed in fresh milk samples in parallel with samples treated by a cycle of freezing and thawing combined with detergent treatment to release the cell-bound NAGase. Before the udder reacted by inflammation, the total NAGase activity consisted of free extracellular activity. Later on when the inflammation was established, much of the milk NAGase remained sequestered intracellularly. S agalactiae was linked with a high degree of cellular NAGase sequestration indicating a blockage of the lysosomal release function from the phagocytes. S aureus delayed the inflammatory response. PMID- 2193332 TI - Effect of intravenous injection of acetate on the pancreas of sheep. AB - The effect of an intravenous injection of acetate on plasma insulin and glucagon concentration was examined in conscious sheep. Sodium acetate (312 to 5000 mumol kg-1 bodyweight) injection increased plasma insulin concentrations in a dose dependent manner. Plasma glucagon concentration was not affected by doses up to 1250 mumol kg-1. Doses of 2500 and 5000 mumol kg-1 produced significant increases (P less than 0.05), but not in a dose related manner. The results of this study indicate that the receptive mechanism of the A cell in the sheep pancreas to acetate might be different from that of the B cell. PMID- 2193333 TI - Regional enteritis in lambs. AB - Thirty-two lambs with regional enteritis were examined. Eighteen were received alive and examined clinically, while the remaining were dead on arrival. One of the sick lambs recovered without treatment. Occurrence and epidemiology, clinical signs, clinical pathology, necropsy findings, light microscopy, immunoperoxidase studies, scanning electron microscopy and transmission electron microscopy are reported. The disease was characterised by stretching of the fore- and hindlimbs, ill thrift, intermittent diarrhoea, leucocytosis, thickened ileal wall and hyperplasia of the ileal mucosa. None of the methods applied revealed any causal agents. Possible aetiological factors are discussed. PMID- 2193334 TI - Pattern of airway response to allergen extract of Phleum pratensis in asthmatic patients during and outside the pollen season. AB - In order to evaluate the pattern of airway response to a specific bronchial provocative test (sBPT) with an extract of Phleum pratensis standardized in biological units (BU), we studied 27 patients with seasonal asthma due to grass pollen by means of allergologic evaluations, methacholine inhalation test and sBPT, outside the pollen season in all patients and, in 10 of them, also during the pollen season. We used a DeVilbiss 646 nebulizer with a dosimeter, giving increasing doses (0.01-2.5 BU) of the allergen solution and we monitored FEV1 to assess early (EAR) and late (LAR) airway responses. Outside the pollen season sBPT elicited an isolated EAR in 16 and a dual asthmatic response (DAR) in 11 patients. We observed no significant difference between EAR and DAR patients as regards the provocative dose causing a 15% fall in FEV1 (PD15FEV1) methacholine, EAR (expressed by PD15FEV1 allergen) or allergologic data. There was a significant relationship between PD15FEV1 allergen and PD15FEV1 methacholine (r = 0.43, p less than 0.05). The reproducibility of sBPT was assessed in 11 patients outside the pollen season. The correlation coefficients between the two tests were: r = 0.91, p less than 0.001 for the total delivered dose of allergen during sBPT; r = 0.79, p less than 0.01 for PD15FEV1 allergen; r = 0.95, p less than 0.001 for the maximum percent fall in FEV1 during LAR. Ten patients repeated all tests during the grass pollen season. PD15FEV1 methacholine and baseline FEV1 decreased significantly during the pollen season, but PD15FEV1 allergen did not change significantly during the season.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2193335 TI - [Systematized temporal delusion and hearing disorders of cortical origin]. AB - We report a case of delusion characterized by a time disorientation with a constant three days advance. Five years previously, the patient had suffered a left hemisphere stroke with aphasia. The delusional belief appeared at the same time as a cortical deafness following a second right hemisphere infarction. There was severe behaviour disturbances which lasted seven months, then cleared without any other change in the clinical picture. The lesions involved the left parietal lobe as well as the temporal and insular regions of both hemispheres. PMID- 2193336 TI - [Chronic subdural hematoma and transient neurologic deficits]. AB - Three cases of chronic subdural hematoma (CSDH) revealed by transient neurological accidents are reported. Although well-known this condition is rare: 1 to 9 p. 100 of CSDHs. Questioning may bring out a history of cranial injury and headache, even minor ones, which are unusual in transient ischemic accidents (TIA). Transient phenomena, such as motor aphasia or speech interruption, point to the diagnosis, especially in male patients over 60 years of age. The finding at electroencephalography of a delta activity more than 48 hours after a TND should exclude the diagnosis of TIA until a CT scan is performed. Since the causes of neurological deficits regressing within less than 24 hours may be ischemia as well a hemorrhage or tumour, the term of transient neurological accident (TNA) should preferably be used, and an emergency CT scan should be performed for diagnostic and therapeutic purposes. Owing to the possibility of another concomitant cause of TNA, the finding of a subdural haematoma should not deter from pursuing cardiovascular examinations. The mechanism of TNA probably involves a vascular factor, as suggested by I-123 IMP cerebral SPECT which shows an intercritical decrease in cerebral blood flow and/or an epileptic factor. PMID- 2193337 TI - [Epilepsy and bilateral occipital calcifications: 3 cases]. AB - We report 3 cases of epilepsy with bilateral occipital calcifications followed up for several years. These cases were compared with 21 published cases and were found to differ from the classical Sturge-Weber syndrome on several points: 1) the disease appeared around the age of 5 years and consisted of focal epilepsy without neurological or mental disorders; 2) the epilepsy was easy to control during 2 to 5 years. This was followed by a diffuse encephalopathy with severe, treatment-resistant epilepsy, Gerstmann's syndrome, optic ataxia, cerebellar syndrome and slow activity at EEG. It appears from these 3 cases that: 1) occipital calcifications may be unilateral at the onset of the disease; 2) visual evoked potentials are affected at a late stage, and 3) CT scans are of considerable value in the prognosis of benign epilepsy in childhood. PMID- 2193338 TI - [Lumbosacral spinal cord infarction. Data from magnetic resonance imaging]. AB - A 77-year old woman and a 61-year old man with lumbosacral spinal cord ischaemic lesions and paraplegia presented with dissociated or partial forms of the lumbar enlargement artery (Adamkiewicz's artery) syndrom. Magnetic resonance imaging (MRI) was performed in both patient with an 0.15 Tesla resistive magnet. A hypersignal on T2-weighted images was present in both cases, which corresponded to the infarction affecting the lumbosacral part of the cord. MRI provided accurate delineation of the lesions and clinicoradiological correlations in both patients. The hypersignal occupied the lumbar cord in case 1 and the conus medullaris in case 2. The clinical signs and location of the lesions seemed to be determined by the different patterns of lumbosacral arterial supply. Since such images could be confused with tumoral images, surgical exploration was carried out in both patients; it failed to demonstrate any tumour or cyst and only showed a pale cord. Surgical cord biopsy in case 2 demonstrated ischaemic tissue. We conclude that ischaemia of the spinal cord can be demonstrated by MRI, but owing to the low specificity of this imaging method aedema cannot be distinguished from necrosis, gliosis or demyelination. PMID- 2193339 TI - [Memory disorders in chickenpox encephalitis]. AB - A 31-year old man with chicken-pox encephalitis presented with a cerebellar syndrome and disorders of memory. The latter consisted of severe anterograde amnesia with normal retrograde memory, without confabulation or anosognosia. This suggested that the hippocampus was involved, probably functionally, since the outcome was rapidly favourable and the MRI was normal. PMID- 2193340 TI - [Cerebellar teratoma in adults. Contribution of x-ray computed tomography and magnetic resonance imaging]. AB - A teratoma of the lower part of the posterior fossa was discovered in a 32-year old woman who was suffering from vertigos and left deafness. The usefulness of CT scan and NMR imaging in the diagnosis of intracranial teratomas is emphasized. PMID- 2193341 TI - [Subacute brainstem hematoma. A surgically treated case]. AB - We report a case of pontine haemorrhage in which symptoms and signs developed over a 2-months period. Surgery was successful but the patient subsequently died. The pathophysiology of subacute and chronic symptoms and signs is discussed. PMID- 2193342 TI - Edward H. Kass, M.D., eulogy. PMID- 2193343 TI - Extrapulmonary Pneumocystis carinii infections. AB - A case of disseminated infection with Pneumocystis carinii is presented, and the English-language literature is reviewed for cases of documented extrapulmonary infection with this organism. In this case--with P. carinii diffusely replacing the bone marrow and causing hepatic, adrenal, and glomerular tuft necrosis--the clinical illness and multiple-organ dysfunction attributed to disseminated P. carinii were more severe than had previously been described. Because the rate of extrapulmonary P. carinii infection found at autopsy in patients with AIDS is at least 2.5% at our institution, we caution against the routine use of aerosol rather than parenteral pentamidine for treatment of P. carinii pneumonia until additional data are available. PMID- 2193344 TI - Cardiovascular and bacteremic manifestations of Campylobacter fetus infection: case report and review. AB - A case of bacteremia due to Campylobacter fetus subspecies fetus with concomitant pleuropericarditis in a previously healthy patient is presented. The organism is ubiquitous, but most commonly causes infection in patients with chronic underlying illnesses. The pathogenesis of human infection has not been definitively elucidated. Bacteremia is the most common clinical manifestation of this infection, although cases of thrombophlebitis, mycotic aneurysm, endocarditis, and pericarditis have also been reported. The treatment of choice for most infections is gentamicin, with chloramphenicol recommended for infection involving the central nervous system. Tetracyclines and erythromycin are alternative agents. Prolonged therapy is essential to the prevention of relapse. A high index of suspicion is necessary for the recognition of this organism in the appropriate clinical settings. PMID- 2193345 TI - Early diagnosis of Nocardia asteroides endophthalmitis by retinal biopsy: case report and review. AB - Hematogenous nocardial endophthalmitis is a rare but devastating infection. Of a total of 10 cases (one described for the first time and nine reported previously in the English-language literature), the lung appeared to be the primary focus of infection in eight (80%). Six (60%) of the cases occurred in individuals receiving corticosteroid therapy; these individuals had undergone renal transplantation (two cases) or cardiac transplantation (one case) and had underlying conditions that included lymphoma (two cases) and chronic active hepatitis (one case). In two immunocompetent individuals, infection followed dissemination from traumatic wounds. Common clinical findings were a rapid decrease in visual acuity and eye pain. All nine of the previously reported cases resulted in total blindness of the involved eye; five patients died not long after diagnosis. In the present report (the first in a cardiac transplant recipient), a favorable outcome with restoration of vision followed early diagnosis through the recently developed technique of fine-needle retinal biopsy. PMID- 2193346 TI - Peritonitis due to Kluyvera ascorbata: case report and review. AB - Kluyvera, a new genus in the family Enterobacteriaceae, was formerly known as enteric group 8 and as API group 1. Although Kluyvera species have been isolated from various clinical specimens such as sputum, urine, stool, and blood, the clinical significance of these isolates has not been established. Recently, we treated a child who developed peritonitis due to Kluyvera ascorbata. The repeated isolation of the organism in pure culture from the peritoneal fluid and its isolation from postmortem subdiaphragmatic microabscesses suggest that Kluyvera can be clinically significant. Review of the literature clearly indicates that Kluyvera strains are infrequent but potentially dangerous pathogens in humans. Further experience is needed to determine the therapeutic efficacy of the various antibiotics to which these bacteria are sensitive in vitro. PMID- 2193347 TI - Facial nerve paralysis and Kawasaki disease. AB - A case of facial nerve paralysis in a patient with Kawasaki disease is described, and 17 cases in the literature are reviewed. A female predominance and a high rate of cardiovascular involvement were noted in patients with facial nerve paralysis and Kawasaki disease. The paralysis was self-limited, resolving without treatment in all surviving patients. PMID- 2193348 TI - Invasive infection with Saccharomyces cerevisiae: report of three cases and review. AB - Saccharomyces cerevisiae (brewer's or baker's yeast) is a common colonizer of human mucosal surfaces, but its role as a clinically important pathogen has been unclear. We report three cases of life-threatening invasive infection with S. cerevisiae resulting in pneumonia, liver abscess and sepsis, and disseminated infection with cardiac tamponade, respectively. A review of the English-language literature reveals 14 other cases of saccharomyces infection in humans. Severe immunosuppression, prolonged hospitalization, prior antibiotic therapy, and/or prosthetic cardiac valves are the settings where saccharomyces infection has been observed. Because Saccharomyces can be a common saprophytic contaminant, biopsy and pathologic confirmation of infection are often necessary for a definitive diagnosis. Amphotericin B is the treatment of choice for serious infections with this organism. PMID- 2193349 TI - Streptococcus pneumoniae infections of the female genital tract and in the newborn child. AB - Streptococcus pneumoniae is not a part of the resident vaginal flora. However, in some women S. pneumoniae can be a transient part of the vaginal flora, and pelvic infection can occur, especially if a predisposing condition exists (e.g., use of an intrauterine contraceptive device, a recent birth, or gynecologic surgery). In the preantibiotic era, pneumococcal genital infection was more common than today, and the rate of lethality was high--26% for localized infection and 74% for peritonitis. During the last 25 years, all 24 patients reported worldwide survived their pneumococcal genital infections, including nine patients at our hospital; in contrast, five of 12 women died between 1938 and 1952. Pneumococci can rarely be isolated as the only pathogen in cases of bartholinitis. Neonatal S. pneumoniae disease with an early onset has an intrapartum pathogenesis. Of 23 reported pediatric patients (including one whom we treated), 48% died and 13% survived with neurologic sequelae. The prognosis for these children has not improved during the last 10 years. PMID- 2193350 TI - Intramedullary tuberculomas of the spinal cord: case report and review. AB - Intramedullary spinal tuberculomas are a rare cause of spinal cord compression. We report a recent case and review 17 cases described in the literature since 1960. Intramedullary spinal tuberculomas occurred in relatively young patients (mean age, 28.6 years) and more frequently in women (63% of cases) than in men. The commonest symptoms were those of subacute spinal cord compression (mean duration, 2.3 months) with progressive lower-limb weakness (94%), paresthesia, and bowel and bladder dysfunction. The major physical finding was paraplegia, either spastic (61%) or flaccid (33%). The majority of patients (55%) had a thoracic sensory level. Extraspinal tuberculous disease, predominantly pulmonary, occurred in 69% of reported cases. Myelography efficiently localized the lesion. The diagnosis was made surgically in 16 patients (89%) and clinically in two (11%). Eleven (65%) of 17 patients improved. Four deaths occurred, three in the perioperative period. Though rare, intramedullary spinal cord tuberculoma should be considered in the differential diagnosis of spinal cord compression, particularly when clinical disease compatible with tuberculosis is present. PMID- 2193351 TI - Pasteurella multocida meningitis in an adult: case report and review. AB - Pasteurella multocida is a rare cause of adult meningitis. Close animal contact prior to onset of illness is frequent and represents the usual mode of introduction of the organism. In reports of a total of 21 cases of P. multocida meningitis in adults (this case report and 20 described previously in the English language literature), 18 researchers commented on the occurrence of animal contact: two cases (11%) involved cat bite, 13 (72%) involved animal contact without bite, and three (17%) occurred in the absence of recognized animal contact. Clinical presentation was typical of bacterial meningitides. Overall mortality rate was 30%. The best predictors of poor outcome were initial hemodynamic instability and age greater than 60 years. Documented bacteremia (40% of cases) was not predictive of higher mortality. Effective therapy is based on early recognition of the possibility of P. multocida meningitis and prompt initiation of treatment with penicillin, ampicillin, or a third-generation cephalosporin. PMID- 2193352 TI - Short-term treatment of uncomplicated lower urinary tract infections in women. AB - Twenty-eight trials conducted on women with uncomplicated cystitis were reviewed comparing various treatment times or various antibiotics administered as single dose or 3-day courses. With all antibiotics, a single-dose was less efficient than a 3-day or greater than or equal to 5-day treatment in eradicating bacteriuria. The difference was more pronounced with beta-lactams than with trimethoprim/sulfonamide combinations. With the latter antibacterial agent, no benefits were achieved by increasing treatment times to greater than or equal to 5 days. Beta-lactam antibiotics were more effective when administered for greater than or equal to 5 days than when given as a 3-day course. Short-term treatment was more effective with trimethoprim/sulfonamide than with beta-lactams. Adverse reactions did not increase with treatment time when penicillins or norfloxacin was used, which was the case with oral cephalosporins. With trimethoprim/sulfonamide combinations, adverse reactions increased markedly when treatment was given for greater than 3 days. In conclusion, single-dose treatment is less efficient than treatment for greater than or equal to 3 days, beta lactams should be administered for greater than or equal to 5 days, the optimal treatment time with trimethoprim/sulfonamide combinations seems to be 3 days, and considerable differences exist among various antibiotics. PMID- 2193353 TI - Gallbladder and biliary tract candidiasis: nine cases and review. AB - We review biliary tract and gallbladder candidiasis and define patient demographics, risk factors, prognostic factors, and treatment strategies for this infection. This is a 3-year retrospective review of our experience with this disease and a review of the English-language literature. Thirty-one cases of biliary tract and gallbladder candidiasis, including nine in our series, have been examined. The same risk factors that predispose patients to other forms of candidal infection are implicated here. No mortality was found with uncomplicated candidal cholecystitis in nonneutropenic patients treated with cholecystectomy alone. Patients with associated extrabiliary tract candidiasis or candidemia had worse outcomes and required both surgical intervention and antifungal therapy. When risk factors exist for the development of biliary tract or gallbladder candidiasis, the physician should be alert to this possibility. There is no need for antifungal therapy in cases of isolated candidiasis of the gallbladder in nonneutropenic patients. PMID- 2193354 TI - Naegleria and Acanthamoeba infections: review. AB - Infections caused by small, free-living amebas are still unfamiliar to many clinicians, pathologists, and laboratorians. As of 31 July 1989, more than 140 cases of primary amebic meningoencephalitis caused by Naegleria fowleri and more than 40 cases of granulomatous amebic encephalitis caused by Acanthamoeba species (including two cases in patients with AIDS) and possibly by other free-living amebas had occurred worldwide. The recent increase in acanthamoeba keratitis (more than 200 cases), especially in contact lens wearers, has generated new interest in this group of amebas. Effective treatment is still lacking. Risk factors, clinical manifestations, and laboratory parameters helpful in the recognition of infections of the central nervous system (i.e., granulomatous amebic encephalitis and primary amebic meningoencephalitis) and acanthamoeba keratitis are reviewed. PMID- 2193355 TI - Bacterial infection as a presenting manifestation of visceral leishmaniasis. AB - Two patients admitted to the hospital because of severe bacterial infection were diagnosed as having visceral leishmaniasis. The types of bacterial infection were perianal abscess and pneumonia; Escherichia coli and Streptococcus pneumoniae were isolated from exudates and blood cultures, respectively. A third patient admitted because of acute necrotizing infection of the pharynx and visceral leishmaniasis is also discussed. Cultures from this patient failed to yield pathogens. Anemia, leukopenia, or thrombocytopenia was present in all patients, and bone marrow aspirate revealed the presence of Leishmania in macrophages. We conclude that in areas where leishmaniasis is endemic, early bone marrow aspirate should, in most instances, be performed in patients with bacterial infection associated with anemia, leukopenia, or thrombocytopenia if hepatomegaly and/or splenomegaly is present. PMID- 2193356 TI - Varied presentations of sporadic group A streptococcal bacteremia: clinical experience and attempt at classification. AB - The epidemiologic, clinical, and laboratory aspects of group A streptococcal bacteremia were studied in 33 patients seen at two urban hospitals in the Tel Aviv (Israel) area, over an 8-year period. Most patients (two-thirds) were female. Clinically significant bacteremia was observed in 26 patients, two of whom acquired their infection (puerperal sepsis) during hospitalization. A portal of entry, mainly cutaneous, was recognized in 61% of the patients, and a chronic underlying condition was observed in 69%. The case-fatality rate was 27%, with death occurring predominantly in patients admitted with shock or cryptogenic bacteremia. Our clinical experience and literature review show that the presentation of group A streptococcal bacteremia is diverse, with transient bacteremia of uncertain clinical significance on one end of the spectrum and overwhelming sepsis on the other. A practical classification of the various clinical forms of group A streptococcal bacteremia is proposed. PMID- 2193357 TI - Prognostic factors in Serratia bacteremia. PMID- 2193358 TI - A memorial minute: Eli Chernin, 1924-1990. PMID- 2193359 TI - Cocaine use during pregnancy. PMID- 2193360 TI - Adolescent substance use and the role of the primary care provider. PMID- 2193361 TI - The physician's role in rehabilitating chemically dependent patients. PMID- 2193362 TI - Cocaine abuse and dependence. PMID- 2193363 TI - [Cytobacteriologic examination of the urine. Execution. Interpretation]. AB - Bacteriological examination of urine is sufficient to assert the presence of a urinary tract infection (UTI). Specimens must be collected under strictly aseptic conditions. The midstream jet method is the best, but when it is not feasible bladder puncture, sterile pouches or catheterization may be used. The urine obtained must be correctly preserved and transported. In the practitioner's office, UTI can be detected by reagent strips or agar-coated plates. In the laboratory, direct examination is used to count leucocytes and characterize Gram positive and Gram-negative bacteria. Bacteriuria at 10(5)/ml is significant of infection. The micro-organisms most frequently responsible for UTI are Enterobacteriaceae (mostly E. coli), Proteus mirabilis, Klebsiella spp. and staphylococci (Staph. aureus, Staph. saprophyticus, Staph. epidermidis). In most cases disc sensitivity tests are indispensable, but bacteriological examination of urine is not always needed in women with uncomplicated lower urinary tract infection. PMID- 2193364 TI - [The 5th consensus conference on intensive care and emergency medicine. Diagnosis of nosocomial pneumopathies in intensive care. 13 October 1989, Bicetre]. PMID- 2193365 TI - [Physiology of the portal system and physiopathology of portal hypertension]. AB - Circulation in the territory of the portal vein is made up of blood flows in the organs of this territory. Each of these organs has an intrinsic and extrinsic regulatory system. Portal hypertension results from a simultaneous increase of intrahepatic portal vascular resistances and blood flow rates. The rise in vascular resistance is due to a decrease of the intrahepatic vascular space consecutive to fibrosis and lesions of the liver cells. The cause of the increase in blood flow is imperfectly known. Physical, metabolic, hormonal and nervous factors may be responsible for these splanchnic circulatory changes, and they also produce changes in systemic haemodynamics. PMID- 2193366 TI - [Non-surgical treatment of hemorrhage caused by portal hypertension in cirrhosis: hemostatic treatment, prevention of the first hemorrhage, prevention of recurrence]. AB - Oesophageal varices are found in two-thirds of cirrhotic patients, and they bleed by rupture in only 50% of the cases. Each bleeding episode carries a mortality risk of about 30%. Recurrences occur in 70% of survivors. Patients with cirrhosis may be considered as being at risk of haemorrhage when large varices, notably with "red signs", are discovered at endoscopy. In two-thirds of the cases, the hemorrhage from ruptured oesophageal varices has stopped by the time emergency endoscopy is performed, but its severity mainly depends on its early recurrence. Haemostatic treatments are justified only in the presence of an active haemorrhage. The best method seems to be endoscopic variceal sclerotherapy carried out in a specialized centre by a centre by a trained endoscopist. The other methods should be used only when sclerotherapy has failed. The prevention of recurrences (secondary prophylaxis) mainly rests on the eradication of varices by endoscopic sclerosis. The addition of propranolol to treatment is probably useful. The seriousness of haemorrhages due to rupture of oesophageal varices justifies primary prophylaxis in patients with large varices found at endoscopy. At present, nonselective beta-blockers constitute the best method of primary prophylaxis. In about 1 out of 5 cases, haemorrhages in cirrhotic patients are due to a different lesion, such as ruptured gastric varices or gastric disease due to portal hypertension. The treatment of haemorrhages causes by these lesions has not been clearly defined, but surgical haemostasis is sometimes indicated in case of ruptures gastric varices. PMID- 2193367 TI - [Paul Leautaud and the Fiessinger-Leroy-Reiter syndrome]. PMID- 2193369 TI - [3 cases of rheumatoid arthritis resulting in systemic lupus 15 years after the onset of polyarthritis]. PMID- 2193368 TI - [5 cases of stress myalgia with tubular aggregates]. AB - The authors report 5 cases of stress myalgias associated with tubular aggregates seen in muscle biopsy specimens. A few similar cases are reported in the literature and a close relationship is established by some authors between the morphologic anomaly present in type II fibers and the lack of tolerance to stress. However, tubular aggregates are not specific and found in other disorders, especially the hyperkaliemic periodic paralysis where all types of fibers are affected. The origin of the aggregates is unknown. They could come from the endoplasmic reticulum containing an excess of calcium and form aggregates in order to prevent a muscle contraction. PMID- 2193370 TI - [Treatment of lumbar disk hernia by intra-disk injection of chymopapain or triamcinolone hexacetonide. Comparative study of 80 cases]. PMID- 2193371 TI - [Osteoradionecrosis of the clavicle after treatment of cancer of the upper respiratory and digestive tract]. PMID- 2193372 TI - [Hypoparathyroidism and homozygote beta-thalassemia. Discussion of a new case]. PMID- 2193373 TI - [Bone infarction, or idiopathic metaphyseal and diaphyseal aseptic osteonecrosis of the long bones. Update and contribution of new imaging technics]. AB - Twenty patients with "idiopathic" bone infarction were studied. There were 18 men and 2 women, age 30 to 69 years, at the time of the diagnosis (mean age = 49 years). Sixty-five lesions were recorded with a marked predominance to the lower extremities (77 p. cent are located around the knees) and to the metaphysis (only three pure diaphyseal lesions). Considered asymptomatic, these lesions were painful in 6 patients. They are multiple, and in this case symmetrical, in 12 patients (60 p. cent). X-Rays disclose the classic heterogeneous ball-like, smoke twirled or encapsulated calcifications. A periosteal thickening opposite the lesions was observed in 6 patients; this may be the only radiological sign. Finally, 18 of the 65 lesions were not visible on standard X-Rays, and obvious on MRI. The MRI aspect is characteristic and may be superposed on the basic lesions already described in the course of aseptic osteonecroses of the femoral head. This is, besides, the most sensitive test, snowing a larger number of more extended necroses than the other examinations. CT scanning as well as scintigraphy present a limited advantage. More than half of the patients also present epiphyseal aseptic osteonecroses, often multiple (55 sites for 13 patients), and often unrecognized. The etiological factors are in fact common to both of these diseases: steroid therapy, alcoholism, dyslipidemia, idiopathic forms. Among the possible causes, the literature mentions lupus erythematosus, renal transplant, cytosteatonecrosis, arteriopathies while there is no post traumatic form. All of the characteristics of these bone infarctions determine a topographic form of the osteonecrotic disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2193374 TI - Photodynamic therapy in gastroenterology. PMID- 2193375 TI - Comparison of blood flow measurements by hydrogen gas clearance and laser Doppler flowmetry in the rat duodenum. AB - This report examines the relationship between hydrogen gas clearance and laser Doppler flowmetry measurements in the duodenum of fasted, anesthetized rats under conditions of 1) reduced perfusion due to graded levels of hemorrhagic hypotension or 2) hyperemia due to perfusion with step doses of acid. There was a significant correlation between hydrogen gas clearance and laser Doppler flowmetry measurements (r = 0.73, p less than 0.01; n = 32 data points in 16 rats). The change in laser Doppler flowmetry values from the period immediately before to the period during the 3 min of acid perfusion was significantly correlated with the dose of acid used (r = 0.51, p less than 0.01; n = 27 rats). The changes in hydrogen gas clearance and laser Doppler flowmetry values from the 30-min period before to the 30-min period after acid perfusion were not correlated with the dose of acid used (r = 0.30 and 0.33, respectively). We conclude that in the rat duodenum 1) the significant linear correlation between hydrogen gas clearance and laser Doppler flowmetry when blood flow is reduced suggests that the countercurrent exchange mechanism is unlikely to modulate significantly hydrogen gas clearance measurements, and 2) the dose-related acid induced duodenal hyperemia is transient rather than persistent when the rat duodenum is exposed to hydrochloric acid (0.03 to 0.1 N) for 3 min. PMID- 2193376 TI - Visual analogue scales for endoscopic evaluation of nonsteroidal anti inflammatory drug-induced mucosal damage in the stomach and duodenum. AB - The use of visual analogue scales in the evaluation of mucosal lesions may reduce sample size requirements in clinical trials, but they may be complex to use, and adding guide points may reduce their informative value. We found that two investigators with differing levels of endoscopic experience reached comparable conclusions in 4 clinical trials (738 scores), and their scores were highly correlated, with similar dispersion characteristics. With guide texts along the scales, thus avoiding points on the actual scales, no tendency towards accumulation was seen in 1449 scores. These results encourage the use of visual analogue scales in endoscopic studies. PMID- 2193377 TI - Terlipressin (triglycyl-lysine vasopressin) controls acute bleeding oesophageal varices. A double-blind, randomized, placebo-controlled trial. AB - The haemostatic effect of terlipressin (triglycyl-lysine vasopressin; Glypressin) on bleeding from oesophageal varices was evaluated in a placebo-controlled, double-blind, randomized clinical trial. Patients with clinically suspected liver cirrhosis were included in the study if they had been admitted to hospital with an extensive haemorrhage within the last 24h before diagnostic endoscopy. The patients randomized after stratification for severity of liver disease. Terlipressin or placebo was administered as intravenous bolus injections every 4th h during a period of 24 to 36 h or until the clinical course necessitated active intervention (failure or withdrawal). Sixty patients entered the study; 31 patients were allocated to receive terlipressin, and 29 patients to receive placebo. Bleeding from varices was arrested in 28 of the 31 receiving terlipressin, as compared with 17 of the 29 receiving placebo (p less than 0.01). Patients receiving active drug required significantly fewer blood transfusions (p less than 0.05). Most of the side effects were classified as mild and were registered in the terlipressin group. PMID- 2193378 TI - Macrophage phenotype within simple ganglia. AB - Immunohistological staining of the connective tissue stroma of simple ganglia using monoclonal antibodies demonstrated infiltrating mononuclear phagocytes. These cells were characterised by positive staining for the leukocyte common antigen, the monocyte associated CD14 phenotype and HLA-class II antigens. There was only occasional expression of an epitope associated with macrophage maturity, and of the iC3b receptor. No expression of the C3b receptor, the high affinity Fc receptor, the p150.95 adhesion molecule or the p8.14 molecule was observed. Polymorphonuclear leukocytes and lymphocytes were absent. The restricted epitope expression by the mononuclear phagocyte population of simple ganglia may be a reflection of the absence of other inflammatory cells and indicates that the micro-environment within inflammatory lesions such as subcutaneous rheumatoid nodules is very different to that present in ganglia. PMID- 2193379 TI - [Late-onset diabetes 1989]. AB - Type II diabetes is a frequent disease among older people (approximately 7% of 60 year-olds in the US). Genetic factors play a more important role in the etiology of type II than of type I diabetes. The metabolic derangements of type II diabetes are due to the combination of a diminished effect of insulin (insulin resistance due to a decreased number of insulin receptors and a postreceptor defect the nature of which is not clear) and a disturbance of insulin secretion. Type II diabetes is associated with a more than doubling of the age-specific mortality, mainly due to diabetic macroangiopathy (myocardial infarctions, cerebrovascular insults). Diet remains the basis of treatment for type II diabetes. The composition of the diet, however, has been altered in that the proportion of carbohydrates has been increased, the proportion of fat decreased and the fibre content increased. If necessary, oral antidiabetics or insulin are added to the dietary treatment. Measurement of C-peptide may help to decide when insulin therapy is required. Measuring HbA1c permits assessment of the mean blood sugar value of the last 1 1/2-2 months. The greatest progress recently made in the treatment of the chronic complications of type II diabetes has been in the field of diabetic retinopathy (photocoagulation for retinopathy lesions, vitrectomy). PMID- 2193380 TI - [Biliary diseases in acquired immunodeficiency syndrome. Apropos of 2 cases]. AB - Biliary complications have recently been reported in patients with AIDS. This may take the form of acalculous cholecystitis or more commonly cholangitis, which may or may not be associated with stenosis of the papilla. These conditions must be sought in patients presenting with right hypochondrial pain and elevated alkaline phosphatase. Infection with Cryptosporidium or cytomegalovirus is often associated. PMID- 2193381 TI - [Hormonal therapy (medical orchiectomy) in prostatic carcinoma]. AB - Hormonal therapy of prostate cancer is still the most effective systemic treatment. Possible alternatives to subcapsular orchiectomy are discussed, comprising the estrogens with their known cardiovascular side effects, the expensive LH-RH analogues, and/or the antiandrogens, which depend on the patient's compliance. Due to more intensive health care and more sensitive diagnostic methods, there is now an increase not only in the overall number of diagnosed prostate carcinomas, but also in the percentage of those which do not need treatment. The question when, and in which patient hormonal treatment should be started becomes increasingly important. PMID- 2193382 TI - [Immunostimulants in chronic infection]. AB - Bacterial extracts are offered as immunostimulatory drugs for the treatment of recurrent infections. A critical review of their postulated immunological efficacy shows that (a) the postulated immunostimulatory efficacy relies mainly on irrelevant in vitro data; (b) the data are inconsistent and contradictory; (c) the immunological efficacy of bacterial extracts given by mouth is doubtful. In addition to the missing immunological basis, various clinical studies have likewise failed to provide a convincing result. The main argument against the use of bacterial extracts as immunostimulants is, however, a wrong indication, as most patients with recurrent infections do not have an immune deficiency but suffer from recurrent infections because of a damaged barrier function (i.e. altered composition of mucus). In spite of these limitations the use of bacterial extracts as "immunostimulants" can be justified, as side effects are very rare, therapy with an "immunostimulant" is attractive for the patient, and the use of antibiotics might be reduced. PMID- 2193383 TI - [Methods of anorectal functional studies]. AB - The currently available methods of anorectal functional investigation are critically reviewed. The clinical utility of manometry has not yet been precisely defined, and the method is not standardized. The principal role of manometry is comparison between defined groups, such as preoperative and postoperative, whereas determination of the degree of continence has proven not more accurate than clinical digital investigation. The latter serves to determine qualitatively all important functions of the anal sphincter components. Radiological dynamic investigations may detect and differentiate various forms of anorectal constipation (outlet obstruction, internal prolapse, rectocele). While electrophysiological studies are not currently used in clinical practice, they demonstrate the importance of pudendal nerve damage in pelvic floor disorders and incontinence. Electromyography may be used to identify the activity of the sphincter components. Clinical investigation may provide detailed and adequate qualitative information on anorectal function. PMID- 2193384 TI - [The etiology and epidemiology of malignant catarrh--a review]. AB - It is generally accepted that both, the wildebeest-derived malignant catarrhal fever (WD-MCF), and the circumstantially evidenced sheep-associated form of the disease (SA-MCF), may be explained as autoimmune disease of various ruminants, namely cattle and farmed deer. The disease follows infection with related herpesviruses being shed by the respective healthy carrier animals. This has convincingly be shown to apply for WD-MCF (Alcelaphine herpesvirus 1, AlcHV1). SA MCF, however, remains to be controversial with both respects. In Switzerland, a serological study indicated that a herpesvirus(es) was highly prevalent among cattle and sheep, inducing antibody that cross-react with AlcHV1 and bovine herpesvirus 4 (BHV4). The latter is known as a largely innocuous agent. A relationship can be demonstrated between the presence of MCF in this country and concurrent serological reactions to both viruses. However similar results may be obtained with healthy animals. Healthy cattle and sheep from farms with or without incidences of MCF displayed the same antibody profiles. It is thus not possible to effectuate meaningful diagnostic tests for (SA-)MCF, nor to confirm any relationship between presumed carrier sheep and the appearance of MCF. PMID- 2193385 TI - [Urachal disorders in calves: clinical and sonographic findings, therapy and prognosis]. AB - Clinical findings, therapy, and prognosis of 20 calves with urachal problems were studied and are discussed. Ultrasonography proved to be a valuable adjunct diagnostic procedure to manual palpation. It allowed exact evaluation of the intraabdominal umbilical cord size and was an important aid in the selection of the correct therapy. A complete omphalourachectomy was performed in calves with an extra- and intraabdominal umbilical cord diameter of up to 10 cm, otherwise drainage was established. Based on our results prognosis for calves with urachitis is independent of the size of the umbilicus and can be judged as favourable in cases without systemic complications. PMID- 2193386 TI - [Current information on the subject of African horse sickness (AHS)]. AB - The objective of the present review was to summarize current knowledge of African horse sickness (AHS), based on available literature (which is nonetheless relatively scant) and recent information obtained from the O.I.E. Brief description is made of the biology of AHS virus (an arbovirus, transmitted by Culicoides imicola), isolation of the agent, diagnosis by serotyping procedures, and preventive measures (such as protection of horses from insect infestation, or vaccination programs) which may be taken. The recent outbreaks in Spain, Portugal, and Morocco, have demonstrated that much more research on this disease is required. PMID- 2193387 TI - [The mammalian pineal gland: a brief survey of its biosynthetic capabilities and physiologic significance]. PMID- 2193388 TI - [Oxygen free radicals and ischemic tissue reperfusion]. PMID- 2193389 TI - [Metabolism of phospholipids on erythrocyte membranes]. PMID- 2193390 TI - [New aspects of prolactin action]. PMID- 2193391 TI - [Isolation and culture of alveolar type II epithelial cells and its uses]. PMID- 2193392 TI - [Prostaglandins and peptic ulcer]. PMID- 2193393 TI - [Current status of the study of mechanisms of liver injury caused by some commonly used hepatotoxic agents]. PMID- 2193394 TI - [Sex hormone receptors of the cardiovascular system and their effects]. PMID- 2193395 TI - [Changes of the retinal structure and mechanisms of their regulation during light and dark adaptation]. PMID- 2193396 TI - Isotopic lead experiment. PMID- 2193397 TI - 32P-postlabeling detection of DNA adducts in fish from chemically contaminated waterways. AB - Fish were collected from sites in the chemically-contaminated Buffalo River, New York, and the Detroit River, Michigan. The sediments of these rivers have high levels of chemical contaminants, including polycyclic aromatic hydrocarbons (PAHs), and fish from these locations have high prevalences of liver cancer. To determine chemical-DNA interactions and a possible role for chemicals as a cause of the observed tumors, DNA was isolated from livers and was enzymatically digested to normal and adducted nucleotides. The DNA digests were enriched for hydrophobic, bulky adducts, either by preparative reverse phase high pressure liquid chromatography, or by selective nuclease P1 dephosphorylation of normal nucleotides. DNA-chemical adducts were then quantitated by 32P-postlabeling analysis. Regardless of the adduct enrichment procedure, the chromatograms derived from DNA of fish from polluted areas showed a diffuse, diagonal radioactive zone consisting, at least in part, of multiple overlapping discrete adduct spots. The behavior of the adducts in the diagonal radioactive zone and of their unlabeled precursors is consistent with their identification as nucleotide adducts of a variety of bulky, hydrophobic, aromatic genotoxic compounds. Analysis of bile demonstrated recent exposure to multi-ringed aromatic compounds. PMID- 2193398 TI - Inside the Gallo probe. PMID- 2193399 TI - The untold story of HUT78. PMID- 2193400 TI - An RNA polymerase II transcription factor shares functional properties with Escherichia coli sigma 70. AB - A mammalian transcription factor, which, along with other factors, is essential for accurate initiation of transcription from promoters by RNA polymerase II, has been found to regulate the interaction of polymerase and DNA. This factor, designated beta gamma, drastically reduces the affinity of RNA polymerase II for free DNA containing either promoter or nonpromoter sequences. In this respect, beta gamma functions as does the bacterial transcription initiation factor sigma 70, which expedites the binding of Escherichia coli RNA polymerase to promoters in part by accelerating dissociation of the polymerase from nonpromoter sites in DNA. PMID- 2193401 TI - Use of the genealogical method in the exploration of chronic illness: a research note. AB - This paper briefly describes how the genealogical method, as derived from Foucault's work, might be used to explore the problem of chronic illness. The genealogical method is differentiated from other qualitative methods, from epidemiology, and from the history of ideas. Finally, the particular relationship, within the genealogical method, of method itself and its object of study is outlined. PMID- 2193402 TI - Child abuse and delinquency: the empirical and theoretical links. AB - There is an association between child abuse and delinquency, but problems with study design, definition, and method currently prevent a definitive understanding of the sequences and causal relations involved. The evidence indicates that a bidirectional relationship exists between child abuse and delinquency. A framework that uses Patterson's analysis of coercive processes suggests that child characteristics, parental inadequacies, and external stressors each play a part in child abuse and delinquency. PMID- 2193403 TI - [Lilian Wald--pioneer of primary health care]. PMID- 2193404 TI - Genome regulation in mammalian cells. AB - A theory is presented proposing that genetic regulation in mammalian cells is at least a two-tiered effect; that one level of regulation involves the transition between gene exposure and sequestration; that normal differentiation requires a different spectrum of genes to be exposed in each separate state of differentiation; that the fiber systems of the cell cytoskeleton and the nuclear matrix together control the degree of gene exposure; that specific phosphorylation of these elements causes them to assume a different organizational network and to impose a different pattern of sequestration and exposure on the elements of the genome; that the varied gene phosphorylation mechanisms in the cell are integrated in this function; that attachment of this network system to specific parts of the chromosomes brings about sequestration or exposure of the genes in their neighborhood in a fashion similar to that observed when microtubule elements attach through the kinetochore to the centromeric DNA; that one function of repetitive sequences is to serve as elements for the final attachment of this fibrous network to the specific chromosomal loci; and that at least an important part of the calcium manifestation as a metabolic trigger of different differentiation states involves its acting as a binding agent to centers of electronegativity, in particular proteins and especially phosphorylated groups, so as to change the conformation of the fiber network that ultimately controls gene exposure in the mammalian cell. It would appear essential to determine what abnormal gene exposures and sequestrations are characteristic of each type of cancer; which agonists, if any, will bring about reverse transformation; and whether these considerations can be used in therapy. PMID- 2193405 TI - The in vitro fertilisation programme at Tygerberg Hospital and the University of Stellenbosch. Five years' experience, April 1983-January 1988. AB - The results of the in vitro fertilisation programme at Tygerberg Hospital for the period April 1983 to January 1988 are presented. Of the 1117 laparoscopies performed, 825 patients reached the transfer stage. A live-birth rate of 9.3% was achieved. The pregnancy rate after transfer of 4 embryos was 25.9% compared with 15.4% after 2 embryos and 10.8% after 3 embryos (P = less than 0.0001). The multiple pregnancy rate was 2.8% in the group receiving 2 embryos and 11.7% and 10.4% in those receiving 3 and 4 embryos, respectively. Of the 77 successful pregnancies (90 babies), 1 baby died at 34 weeks' gestation as the result of abruptio placentae due to preeclampsia and 1 cot death occurred. The only congenital abnormality encountered was a cleft palate. PMID- 2193406 TI - Acute dichromate poisoning after use of traditional purgatives. A report of 7 cases. AB - Seven cases of dichromate poisoning after the use of purgative solutions obtained from nyanga (traditional township healers) are reported. The patients all presented in established renal failure requiring dialysis, and all had abnormal liver function tests. One patient who took dichromate orally died from massive gastro-intestinal haemorrhage. Six patients took dichromate solutions as rectal enemas, 2 were left with impaired renal function and 1 required a permanent colostomy as a result of extensive peri-anal necrosis. The clinical presentation of acute renal failure, gastro-intestinal haemorrhage and hepatocellular dysfunction should alert the physician to the possibility of dichromate poisoning. The diagnosis, management and the role of dialysis in dichromate poisoning are reviewed. PMID- 2193408 TI - An evaluation of oligoclonal banding and CSF IgG index in the diagnosis of neurosyphilis. AB - It can be difficult to determine which patients would benefit from therapy to control central nervous system infection with Treponema pallidum. The authors have followed patients prospectively to evaluate two new diagnostic tests available. They performed lumbar punctures on 107 consecutive patients with syphilis of unknown duration, untreated (n = 19) or with serology that did not decrease sufficiently during follow-up (n = 88). The mean age was 47 years, with 91 males and 16 females. Twelve had neurologic symptoms. In order to establish a gold standard, the authors required the cerebrospinal fluid Venereal Disease Research Laboratory (CSF VDRL) test to be reactive (n = 25). They then examined oligoclonal banding and CSF IgG index as diagnostic tests by comparing them to the gold standard. Oligoclonal banding, abnormal in 20, had a sensitivity of 52% and a specificity of 91%. The CSF IgG index, abnormal in 56, had a sensitivity of 92% and a specificity of 60%. The posttest likelihoods of a positive test result were low, and hence neither test ruled in the diagnosis. With a post-test likelihood (PTL) negative of 4%, a negative CSF IgG index assisted in ruling out the diagnosis. Oligoclonal banding was not a satisfactory test for neurosyphilis. The CSF IgG index appears to help only in ruling out infection. Further effort is needed in developing diagnostic tests to assist the clinician in the diagnosis of neurosyphilis. PMID- 2193407 TI - Treatment of asymptomatic amebiasis in homosexual men. Clinical trials with metronidazole, tinidazole, and diloxanide furoate. AB - In a randomized trial, the authors treated 42 asymptomatic homosexual men who had Entamoeba histolytica in fecal specimens with either metronidazole or tinidazole (study 1). They treated both groups initially with 2,000 mg in a single dose, and in case of failure with 2,000 mg daily for 5 days. In cases of repeated failure, the authors prescribed a dosage of 500 mg of diloxanide furoate three times per day (TID) for 10 days. In a subsequent study (study 2) the authors treated 49 asymptomatic homosexual men who had E. histolytica in fecal specimens with 500 mg of diloxanide furoate TID for 10 days. In study 1, the parasitological cure rates (PCR) for metronidazole and tinidazole were 29%-56%. Among the men treated with diloxanide furoate, the PCR was 93%. In study 2 the PCR with diloxanide furoate was 88%, which was significantly better (P less than .05) than metronidazole/tinidazole treatment in study 1. The present studies show that diloxanide furoate is an effective treatment of amebiasis in asymptomatic patients. PMID- 2193409 TI - Social Security related legislation in 1989. PMID- 2193410 TI - [Congenital malformations--multiple abnormalities syndromes]. PMID- 2193411 TI - [Chromosome abnormalities--prenatal diagnosis]. PMID- 2193413 TI - Rectovaginal fistula or perineal and anal sphincter disruption, or both, after vaginal delivery. AB - The management of 52 patients with rectovaginal fistula or perineal and anal sphincter disruption, or both, after vaginal delivery is presented. Adequate physical intestinal preparation and postoperative diet and intestinal care are stressed. Preservation of perineal integrity is suggested whenever possible. Closure in anatomic layers is the technique of choice and sphincterotomy is advised in all instances of anal sphincter anastomosis. The technique for repair of an extensive cloacalike lesion is described in detail, as are three unusual complications of operation. Satisfactory anatomic and functional results were obtained in 100 per cent. PMID- 2193412 TI - Colposuspension for urinary stress incontinence in premenopausal and postmenopausal women. AB - Sixty-nine premenopausal and 53 postmenopausal women had a colposuspension operation for urinary stress incontinence. A significant postoperative reduction (p less than 0.001) of symptoms of frequency, nocturia, urgency and urge incontinence was obtained in both groups. Postoperatively, 88.4 per cent of the premenopausal women were found to be dry compared with 66 per cent in the postmenopausal group (p less than 0.01). No differences were found preoperatively and postoperatively in the cystometric values or in the urethral pressure profiles at rest in both groups and between the groups. The pressure transmission ratios were significantly improved postoperatively in both groups. The postoperative transmission ratios in the premenopausal women were found to be significantly higher than those in the postmenopausal group, at the middle two quarters of the urethra. Although surgical treatment for urinary stress incontinence in postmenopausal women results in lower cure rates than in younger women, it should be considered. PMID- 2193414 TI - Colposacropexy with Prolene mesh. AB - A retrospective analysis of 59 patients who underwent colposacropexy (CSP) using Prolene (polypropylene) mesh is presented. Fifty-eight of the patients had undergone previous surgical treatment, including either vaginal or abdominal hysterectomy. Twenty-two patients underwent CSP alone, 24 had CSP and retropubic urethropexy (RPU), eight had CSP with anterior or posterior repair, or both, and five had CSP and RPU with anterior and posterior repair. The operations were associated with a minimum of intraoperative complications and acceptable postoperative problems. A postoperative questionnaire was sent to the patients with an 89 per cent response rate. None of the patients complained of protrusion from the vagina. It is concluded that, in the hands of experienced surgeons, CSP is a safe, efficacious operative procedure that should remain the procedure of choice for vaginal vault prolapse since it restores the normal vaginal axis, maintains existing vaginal length and provides permanent care. PMID- 2193415 TI - Guidelines for therapeutic decision in incidental appendectomy. AB - Incidental appendectomy is contraindicated in patients whose conditions are unstable, patients previously diagnosed with Crohn's disease, patients with an inaccessible appendix, patients undergoing radiation treatment, patients who are pathologically or iatrogenically immunosuppressed and patients with vascular grafts or other foreign material. In patients ten to 30 years of age--the age group associated with a higher incidence of acute appendicitis--who are otherwise healthy, incidental appendectomy is effective in preventing morbidity and death associated with acute appendicitis. In patients 30 to 50 years of age, incidental appendectomy should be left to the discretion of the surgeon. In this age group, the physician should give special consideration to the gender of the patient and the desire for future childbirth. In patients more than 50 years of age, the incidence of acute appendicitis decreases and the risk associated with operation and prolonged anesthesia is such that an incidental appendectomy is not beneficial. In mentally handicapped patients less than 50 years of age and who are physically healthy, incidental appendectomy should be performed. An inversion technique should be used in all instances of incidental appendectomy. In otherwise clean cases in which incidental appendectomy is anticipated, prophylactic antibiotics may be of value. Patients undergoing procedures that may compromise access to the appendix in the future should undergo incidental appendectomy. PMID- 2193416 TI - Dermoid cysts of the posterior cranial fossa in children. Report of nine cases and review of the literature. AB - Dermoids of the posterior cranial fossa in children are rare. We report the clinical and pathological data on nine children with these lesions. A mean follow up of 17.3 years after total removal confirms the excellent prognosis irrespective of whether the presenting symptom is meningitis or intracranial hypertension. A brief review of 39 published cases follows. PMID- 2193417 TI - Cruciate hemiplegia: a clinical syndrome, a neuroanatomical controversy. Report of two cases and review of the literature. PMID- 2193418 TI - A recollection of five of the charter members of the Society of Neurological Surgeons. PMID- 2193419 TI - As it was at the beginning. An essay to commemorate the 50th anniversary of the founding of the Society of Neurological Surgeons. PMID- 2193420 TI - [Ski boots versus the knee joint. 2: What produces the forward leaning position of the ski boot?]. AB - In contrast to the drop in the incidence of fracture of the lower leg that has been observed in recent years, the incidence of knee injuries has not decreased in skiing. There has even been a relative increase of severe knee lesions and isolated ACL ruptures, prompting us to conduct a comprehensive study of the causes of this phenomena. The goal of part 2 of the study was to comprehensively examine the forward movement in skiboots in the lab and on the slope. Studying nine beginners and eight experts, we found a 20% (sign. 0.05) lower forward-lean capability for the beginner group in the same boot. A randomized study with crossover design conducted on the slope, where we equipped 16 skiers with either soft or stiff boots for the duration of five ski days, revealed the learning behaviour and forward position on the slope depending on the boot. The pupils became definitely less adept at learning if they were required to wear stiff skiboots and showed a sign, lower forward flex angle. A skiiing style in backward lean position was adopted and supported by the fixed backward spoiler. Therefore another study was necessary and will follow (part 3) to examine the effect of a stiff backward spoiler and skiing in a backward lean position. In consideration of the facts known up to now, it is concluded that to improve safety in skiing recommendations must be given as to which boot to choose, according to the skiing level. In addition, the setting of safety bindings must consider the type of skiboot used. PMID- 2193421 TI - [Load capacity of capsule and tendon tissue]. AB - The data referred to in this article show that the load capacity values of capsular and tendinous tissue are significantly higher than had been assumed so far; this applies to the macroscopic as well as the microscopic and submicroscopic ranges and is also based on our own experimental studies, which were mainly focussed on load capacity and tissue damage. For example, the tear resistance to static load is 50% higher and to dynamic load 100% higher than most of the maximum load data known so far. Thus, the dynamic tear resistance exceeds the static resistance by one third. The maximum load capacity decreases with increasing age; the peak value is attained at about the third decade of life. Tear resistance is related to the smallest cross-section of the tendon. It has been safely established that cross-section and tear resistance decrease with advancing age. There is definite mathematical and histological proof that even a healthy tendon can tear under unfavourable load conditions and can thus well be the weakest link in a healthy muscle-tendon-bone system. This fact assumes increasing importance in these times of increasing leisure and sports activities practised by persons of all age brackets. The commonly used terms of "load" and "load capacity" thus acquire a new dimension. We know that the load exercised on a tendon is permanently increased especially in sports activities. We also know that load capacity can be promoted. Hence, it depends on us to learn how to master the functioning of the tendon and to develop measures to help to avoid acute and chronic tendon damage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2193422 TI - [An innovative concept for primary functional treatment of Achilles tendon rupture]. PMID- 2193423 TI - [Long-term results following subcutaneous Achilles tendon rupture]. AB - From 1972 to 1982, 132 ruptures of the achilles tendon were treated at the Orthopedics Division, University of Heidelberg. Surgical treatment was carried out in 125 cases, and seven patients were treated conservatively. The average age of the patients was 42 years. 84% of the achilles tendon ruptures occurred during sport. After an average investigation period of 6.5 years, 33 patients could be followed up. The rate of complications and the final functional results are communicated. The blood supply to the achilles tendon is described separately. Twelve cadaver achilles tendons were investigated by means of the plastination method. It could be demonstrated that a reduced blood supply to the Achilles tendon is present about 3-5 cm above the calcaneal tuber. This finding corresponds to the most frequent site of rupture. It is unclear to what extent there is a connection between the blood supply and the rupture site of typical locations. PMID- 2193424 TI - [Treatment of fresh muscle injury]. AB - A prospective double-blind randomized study comparing the results of a protein free-haemodialisate (Actovegin) with placebo was performed in 103 patients. There has been 68 patients in the haemodialysate group. In acute muscle injuries we find a dent in the muscle and a loss of function. There has been three injections in the injured muscle every three to four days. The follow up examination occurred at least three months after the beginning of the study. Full sports activity was reached in the haemodialysate group after 5.5 weeks, in the non haemodialysate group after 8.3 weeks. There has been a significant difference in the time of rehabilitation between the shank and the thigh muscles. The results show a high statistic significance. PMID- 2193425 TI - The "right stuff": five Nobel Prize-winning surgeons. AB - Alfred Nobel's will specified that his estate be placed in a fund, the interest of which was to be distributed on an annual basis "to those who during the preceding year had conferred the greatest benefit on mankind." The first Nobel Prize in Physiology or Medicine was awarded in 1901, and its receipt is widely regarded as one of the highest accolades in science. This article reflects upon five surgeons who have been recognized as worthy of this honor. They are Emil Theodore Kocher, Alexis Carrel, Frederick Grant Banting, Werner Theodor Otto Forssman, and Charles Brenton Huggins. By winning this coveted prize these men have elevated the discipline of surgery to the summit of the scientific world. We review their legacy as an inspirational reminder of what we, the future of surgery, are capable. PMID- 2193426 TI - Heterotopic gastric mucosa in the common bile duct. AB - Gastric heterotopia within the biliary system is rare and is generally an incidental finding. Only a few patients have biliary symptoms specifically attributable to heterotopia. A unique case of symptomatic gastric heterotopia of the common bile duct is presented and the literature reviewed. PMID- 2193428 TI - Improvement of the quality of frozen sections from formalin fixed tissue. PMID- 2193427 TI - Determination of plasma cell labelling index with bromodeoxyuridine using a double immunoenzymatic technique. AB - Myeloma plasma cells were double stained using peroxidase and alkaline phosphatase labelled monoclonal anti-BrdU and anti-intracytoplasmic immunoglobulins. Samples were methanol fixed; DNA was denatured with formamide. The results allowed easy identification of plasma cells, their cytological examination and the calculation of percentage of plasma cells in S phase. Good correlation was found with the labelling index obtained with tritiated thymidine. PMID- 2193429 TI - A method to determine the end point of decalcification of hard tissue and bone. AB - A method for decalcification end point determination of mineralized tissue is described. The calcium content of the decalcification solution was determined colorimetrically with a "continuous automatic analyzer" with a high degree of accuracy. The end point method used has been tested on two decalcification methods, 5% nitric acid with or without ultrasonic treatment. The results suggest it is possible to quantitate the decalcification process. PMID- 2193430 TI - Lansteiner Award. Some aspects of serological specificity. PMID- 2193431 TI - Why do they give the gift of life? A review of research on blood donors since 1977. PMID- 2193432 TI - An ATP-driven pump for secretion of yeast mating factor. PMID- 2193433 TI - Does protein phosphorylation play a role in translational control by eukaryotic aminoacyl-tRNA synthetases? AB - In addition to their primary role in tRNA charging, aminoacyl-tRNA synthetases can regulate protein synthesis in eukaryotic cells. Although the phosphorylation of these enzymes themselves has little effect on their catalytic activity, there may be a role for protein phosphorylation in mediating their regulatory effects. PMID- 2193434 TI - Bacterial genetics by electric shock. AB - Subjecting bacteria to a high-voltage electric discharge renders the cells permeable to DNA. This powerful method allows the genetic manipulation of bacterial species that cannot easily be transformed by conventional techniques. PMID- 2193435 TI - Structure of the human centromere at metaphase. AB - Until recently the centromere was thought to be a relatively homogeneous region of densely packed heterochromatin with a single differentiated domain--the kinetochore--at its surface, representing the point of attachment of the mitotic spindle. We now know that the centromere of higher eukaryotes is composed of several domains that have been identified using antibody probes. Somewhere within the domains are located both the factor(s) that control the disjunction of sister chromatids and the molecular motor responsible for chromosome movement towards the spindle poles. PMID- 2193436 TI - The where, what and how of ribosomal frameshifting in retroviral protein synthesis. AB - The gag and pol genes of most retroviruses occur in different reading frames and their translation as a single polypeptide is carried out by ribosomal frameshifting in the -1 direction. The alignment of the different reading frames occurs by overlapping reading in response to at least two signals within the RNA: one is a heptanucleotide stretch at the frameshift site and the other is a stem loop structure which occurs just downstream of the first signal. PMID- 2193437 TI - Logic of the Escherichia coli cell cycle. AB - The logic of Escherichia coli's responses to environmental changes gives hope that its cell cycle will be equally well designed. During growth in a constant environment, internal signals trigger cell-cycle events such as replication initiation and cell division. Internal signals must also provide the cell with information about its present state, enabling it to coordinate the synthesis of cytoplasm, DNA and cell wall and maintain proper cell shape and composition. How the cell regulates these aspects of its growth is a fascinating--and as yet unfinished--story. PMID- 2193438 TI - Ubiquitin-conjugating enzymes: novel regulators of eukaryotic cells. AB - Covalent attachment of ubiquitin to cellular proteins is essential for cell viability and is catalysed by a set of distinct ubiquitin-conjugating enzymes. Individual members of this novel enzyme family mediate strikingly diverse functions, including DNA repair, cell cycle control, selective protein degradation and essential functions of the stress response. PMID- 2193439 TI - The retinoblastoma gene and cell growth control. AB - Rare diseases often provide unique and fascinating insights into the workings of biological machinery. Retinoblastoma is a good example. This hereditary disease occurs rarely (in only one out of 20,000 children), yet it opens a 'window' into the mechanisms that sit at the very center of growth control in cells throughout the body. Children who survive bilateral retinoblastoma often have offspring who are similarly affected. Indeed, transmission of the disease suggests the actions of a simple dominant Mendelian allele of high penetrance. Three years ago the wild-type allele of this gene (termed Rb) was isolated by molecular cloning. With this success has come a rich harvest of information on tumor pathogenesis and the molecular biology of cellular growth control. PMID- 2193440 TI - Through the looking glass: the discovery of supercoiled DNA. AB - The discovery of supercoiled DNA was first reported 25 years ago in a paper entitled, 'The Twisted Circular Form of Polyoma Viral DNA' by Vinograd, Lebowitz, Radloff, Watson and Laipis. This personal reflection describes the different experimental and conceptual processes that eventually led to the discovery as they actually occurred. PMID- 2193441 TI - Urinary insulin level as an indicator of graft function after porcine pancreatic transplantation. AB - Urinary levels of immunoreactive insulin (IRI) were measured in 18 pigs subjected to pancreatic allograft transplantation with exocrine drainage into the urinary tract. Fifteen pigs were given no immuosuppressive therapy while 3 pigs received cyclosporine and prednisolone. The onset of rejection was defined as an increase in the serum levels of anionic trypsin (irAT). Urinary levels of IRI were compared between normo- and hyperglycemic pigs representing slow and fast rejectors. It was possible to measure insulin in the urine from all these pigs with a pancreatic allograft, and the urinary IRI levels increased after an intravenous injection of secretion and cholecystokinin. We found that urinary IRI response to secretin and cholecystokinin declined during rejection. By contrast, baseline, unstimulated urinary IRI levels did not correlate with rejection. No advantage was seen in the determination of urinary IRI when compared to determination of urinary irAT. In pigs not treated with immunosuppressants (with irreversible rejection), stimulated urinary levels of IRI and irAT were highly useful as graft-function indicators, whereas in immunosuppressed pigs (with reversible rejection episodes) they seemed to complement each other. PMID- 2193442 TI - Chronic cyclosporine-associated nephrotoxicity in bone marrow transplant patients. AB - This study describes the prevalence and degree of chronic cyclosporine-associated nephropathy and its risk factors. For this purpose we reviewed all available renal histology specimens in 169 bone marrow transplant recipients treated during an eight year period with cyclosporine for prevention of graft-versus-host disease, and determined their pattern and degree of histomorphological changes. A total of 51 specimens obtained from 49 patients by biopsy (n = 12) or autopsy (n = 39) was evaluated. The pattern of histomorphological changes was compared with diagnosis, age, sex, and potential risk factors--such as cyclosporine dose, levels, duration of therapy, changes in serum creatinine and onset of hypertension. Morphological lesions of chronic cyclosporine-associated nephropathy were found in 67% of the specimens. They were more frequent and more severe with increasing duration of cyclosporine therapy, in patients with a higher increase in serum creatinine during the first 3 months and in patients given total-body irradiation for conditioning. These latter findings suggest that additional damage sensitizes the kidney to irreversible toxic effects of cyclosporine. PMID- 2193444 TI - Pig fetal pancreatic monolayers. A model of potential use in transplantation. AB - Endocrine-rich monolayers of pig fetal pancreas that are free of fibroblasts have been established with the ultimate aim of providing guidelines for the culture of the human equivalent. The immunogenic potential of the monolayers--hence their capacity to be grafted--has also been analyzed. Fetuses ranging from 50 to 90 days were used, and, following digestion with collagenase (4 mg/ml, 15-20 min), the pancreatic suspension was plated onto tissue culture vessels containing RPMI 1640. The fetal calf serum concentration was kept low (5%) initially to inhibit fibroblast proliferation, but subsequently increased to 7%. Monolayers from a typical litter of 8-10 fetal pigs produced 6-8 x 10(8) viable epithelial cells by day 10 of culture, of which 75% were endocrine cells. This represents an 8-fold increase in a two-week period. The ratio of beta:alpha:delta:pancreatic polypeptide cells was 19:33:18:5. These monolayers synthesized both DNA, (pro)insulin and protein, and displayed increased insulin release when exposed to 10 mM theophylline, 10 mM Ca2+ and 1.3 microM 12-0-tetradecanoyl-phorbol-13 acetate. Static stimulation with 20 mM glucose however, did not elicit a response in insulin secretion. These cells displayed no reaction to allogeneic lymphocytes in a mixed lymphocyte culture, whereas freshly obtained porcine epithelial cells did. Methods may need to be found to increase the proportion of B cells in this enriched endocrine cell population. In general however, guidelines have been established that may be useful in developing a monolayer of human fetal pancreatic cells with the eventual aim of transplantation. The reduction in immunogenicity of the pig fetal pancreatic cells suggests that they too might be a potential source for transplantation. PMID- 2193443 TI - A European multicenter study of chronic graft-versus-host disease. The role of cytomegalovirus serology in recipients and donors--acute graft-versus-host disease, and splenectomy. AB - A group of 466 leukemic bone marrow transplanted patients were reported from 17 European bone marrow transplantation teams. Of these, 285 survived more than 3 months and could be evaluated for chronic GVHD. The cumulative incidence of chronic GVHD was 32% two years after BMT. The following factors were statistically significantly associated with chronic GVHD in bivariate analysis: high donor and recipient age, splenecacute GVHD, pretransplant seropositivity to CMV among the recipients and the donors, and donor seropositivity to 3 or 4 different herpesviruses, compared with 0-2, prior to BMT. In multivariate analysis pretransplant recipient CMV seropositivity in combination with donor CMV seropositivity prior to BMT (P = 0.0006), a previous grade II-IV acute GVHD (P = 0.001), and splenectomy (P = 0.01) were significantly associated with chronic GVHD. Thus, in addition to acute GVHD, CMV immune donor cells may be triggered by latent CMV in the recipient, which may play a role in the triggering of chronic GVHD. The possible role of splenectomy in GVHD is also discussed. PMID- 2193445 TI - Severe endothelial injury in a renal transplant patient receiving cyclosporine. PMID- 2193446 TI - Malacoplakia of the prostate masquerading as a rectal tumor in a transplant recipient. PMID- 2193447 TI - [Migraine aura--vascular or neuronal disease?]. AB - During the migraine-aura cerebral blood flow (CBF) is reduced in areas corresponding to the neurological deficits and symptoms. Whether this CBF reduction is the primary cause of the neurological deficits (the vascular theory) or a secondary result of primary neuronal dysfunction in particular "spreading depression" (SD) (the neurogenic theory) is still under discussion. The latter theory is supported by CBF investigations performed during attacks of migraine with aura (MA). The CBF reduction was found to be modest (20-35%) and not sufficient to cause ischemia which usually demands reduction of CBF by more than 50%. In addition the low-flow area appeared to "spreading" in the same manner as that seen in SD in the rat ("spreading oligemia"). Recent studies indicate, however, that the CBF reduction in most cases, after all, is sufficient to cause ischemia and that "spreading oligemia" might be an artifact caused by "scattered radiation". Persistent neurological deficits, EEG abnormalities and infarcts on CT-scans are seen after MA, thus further supporting the theory of vascular dysfunction (vasospasm) and ischemia as the cause of the migraine-aura. PMID- 2193448 TI - [Isoptin Retard. Pharmacokinetics and pharmacodynamics in patients with angina pectoris]. AB - Sustained-release Verapamil is suitable for treatment of angina pectoris. The initial dose should be 240 mg administered at bedtime. If the desired effect is not obtained, the dosage may be increased first to 360 mg at bedtime and then to 240 mg morning and evening. In patients already receiving treatment with standard Verapamil, this may be replaced by Sustained-release Verapamil mg for mg. In long term treatment the half life is increased and reduction of the dosage should, therefore, be attempted. PMID- 2193449 TI - [Genital tuberculosis in women]. AB - Recent literature concerning genital tuberculosis in women is reviewed. In Denmark, 25% of the cases are observed in immigrants. The symptoms are non specific in the form of infertility, metrorrhagia or abdominal pain. Positive culture or specific histology are necessary to establish the diagnosis. Approximately one third of the cases are recognized first during or after operation in connection with laparotomy on suspicion of another condition. Treatment is primarily combined therapy with rifampicin, isoniazide and ethambutol for nine months. If treatment fails or pain persists, total hysterectomy and bilateral salpingectomy are indicated. Bilateral oophorectomy in younger patients with normal ovaries has been discussed. The prognosis as regards survival is good but the patients must be considered to be infertile. PMID- 2193451 TI - Fifteenth International Symposium on Ultrasonic Imaging and Tissue Characterization. June 11-13, 1990, Arlington, VA. Abstracts. PMID- 2193450 TI - [Urinary retention in connection with postoperative pain treatment with epidural opioids]. AB - The incidence of retention of urine in cases of postoperative epidural opioid analgesia varies from 15% to 90%. The extent to which this phenomenon depends upon the dosage employed has not been elucidated. The cause of postoperative retention of urine (PU) is probably a combination of the central and peripheral effect of the opiate involving altered autonomic activity. Increased sympathetic activity resulting from surgery may, similarly, be a pathogenetic factor. The current methods of treatment are prophylactic or symptomatic alpha-receptor blockade, naloxon in refractory doses or catheterization. Inhibition of per- and postoperatively increased sympathetic activity may possibly prevent PU. Carbacholine is not effective in the treatment of postoperative retention of urine. In animal experimental studies, kappa-receptor agonists have an analgesic effect without urodynamic side-effects but no clinical trials on man have hitherto been undertaken. When postoperative retention of urine occurs after epidural opioid treatment, clean intermittent catheterization or introduction of a thin suprapubic catheter are recommended. PMID- 2193452 TI - Preliminary results for shear wave speed of sound and attenuation coefficients from excised specimens of human breast tissue. AB - A pilot study involving 53 specimens of excised human female breast tissue was performed to provide preliminary estimates of the acoustic shear wave speed of sound and linear attenuation coefficient associated with high risk for development of invasive breast cancer. The measured shear wave properties were studied as a function of: 1. whether the tissue was presented as a 2.0 to 4.0 gram mass biopsy sample or a 2.0 to 4.0 gram mass subsample taken from a larger mastectomy source; 2. the time post-excision prior to shear wave characterization; 3. the risk factor associated with the number and types of lesions found in the specimen; and 4. the percent by volume of fat or collagen present in the sample. The shear speed of sound was found to range between 20 and 900 m/s with a tendency for lower speeds as a function of time post excision. The results for shear attenuation coefficients ranged from 300 to 9000 cm-1 and did not show a marked time dependence. Average results from mastectomy specimens differed from those for biopsies, but the difference may have been due to variations in tissue composition and time post excision before shear wave characterization. PMID- 2193453 TI - [A cerebral hernia of the postoperative mastoidal cavity (current aspects of the problem)]. PMID- 2193454 TI - [Aleksandr Fedorovich Prussak--the first Russian professor of otiatrics (on the 150th anniversary of his birth)]. PMID- 2193455 TI - Correct Medicare billing benefits patients. PMID- 2193456 TI - Trends in the management of splenic trauma. AB - During the 20-year period ending December 1987, 179 consecutive splenic trauma patients were treated at a single institution. Procedures included splenectomy in 121 (67%) patients, splenectomy with autotransplantation in 7 (4%), splenorrhaphy in 23 (13%), laparotomy alone in 7 (4%), and nonoperative management in 21 (12%). Before 1976, all patients were treated by splenectomy. Since 1980, 18 (22%) were treated nonoperatively, 26 (33%) by splenic salvage techniques, and 36 (45%) by splenectomy. We conclude that nonoperative therapy and splenic salvage techniques are being employed with increasing frequency. Selective application of splenorrhaphy for injuries with a realistic expectation of success has resulted in no late procedures for hemorrhage. In the presence of severe splenic or associated injuries, splenectomy remains the procedure of choice. PMID- 2193457 TI - Amphotericin B dilution. PMID- 2193458 TI - Doxepin in smoking cessation. PMID- 2193459 TI - Nocturnal leg cramps. PMID- 2193460 TI - Anistreplase: a novel thrombolytic agent for acute myocardial infarction. AB - Anistreplase, a modified congener of streptokinase, is a recently approved thrombolytic agent used in the treatment of acute myocardial infarction (AMI). Clinical studies have demonstrated anistreplase to be equally efficacious as intracoronary streptokinase when given within four hours of the onset of chest pain. Thirty units, given as a single bolus intravenous injection, result in reperfusion rates of approximately 60-70 percent. The adverse-effect profile of anistreplase compares favorably with that of streptokinase, with hemorrhagic complications being the most serious. Anistreplase has two distinct advantages over both streptokinase and alteplase: (1) it can be administered as a single bolus intravenous injection and (2) it has a longer half-life which may result in decreased reocclusion rates. Anistreplase therapy is associated with reductions in both short- and long-term mortality and has been shown to preserve left ventricular function. A large, long-term, comparative clinical trial (Third International Study of Infarct Survival or ISIS-III) investigating morbidity and mortality rates with streptokinase, alteplase, and anistreplase is ongoing, as is a direct comparative study against alteplase alone (TEAM-3, Multicenter Thrombolytic Trials of Eminase in Acute Myocardial Infarction). PMID- 2193461 TI - Flutamide: an antiandrogen for advanced prostate cancer. AB - Flutamide is a nonsteroidal pure antiandrogen that acts by inhibiting the uptake and/or binding of dihydrotestosterone to the target cell receptor, thus interfering with androgen action. Flutamide is well absorbed orally and extensively metabolized; its active metabolite, 2-hydroxyflutamide, is formed rapidly and excreted almost entirely by the kidneys. Clinical studies in prostate cancer patients have demonstrated efficacy with flutamide monotherapy in patients who had received no prior treatment, in untreated patients with combined androgen blockade concomitantly with a luteinizing hormone-releasing hormone (LHRH) agonist, and in relapsed patients. A randomized, placebo-controlled trial demonstrated a 26 percent increase in median survival for patients treated with leuprolide plus flutamide compared with leuprolide plus placebo. When given as monotherapy and in combination with an LHRH-agonist, flutamide is well tolerated. The usual adverse effects are gynecomastia and mild diarrhea when given as a single agent. In combination with an LHRH-agonist, hot flashes, loss of libido, impotence, mild nausea and vomiting, gynecomastia, and diarrhea are commonly reported. However, only diarrhea occurred more frequently in patients treated with leuprolide plus flutamide than in those treated with leuprolide plus placebo. Flutamide is indicated in combination with an LHRH-agonist (e.g., leuprolide) as initial therapy in metastatic (stage D2) prostate cancer. The usual dose is 250 mg po tid given at eight-hour intervals and started concurrently with the LHRH-agonist. Formulary addition is recommended. PMID- 2193462 TI - [150 years of medical mycology]. AB - A short survey concerning the development of the medical mycology is presented covering the last 150 years (1839-1989). According to the interpretation of most of the distinguished authors, the year of Schonlein's publication, i.e. 1839, is to be considered as the origin of the medical mycology. Therefore, mycoses were the first infectious diseases the etiology of which were scientifically explained. Monographs and articles in manuals written in the most important world languages represent milestones in the historical development. Over large periods connected to and promoted by dermatology, increasingly this special field has developed to an important and autonomous part of medical microbiology. PMID- 2193463 TI - [Venous diseases in workers with jobs requiring standing]. AB - In relation to the social medical importance of venous diseases the possible association between venous diseases and standing position is pointed out in the literature. Derived from this the necessity is resulting for occupational medicine to collect data in follow-up studies which may lead to precise criteria for job fitness examinations. PMID- 2193464 TI - [Viewpoints on preparations for integrating data processing systems in routine microbiology diagnosis]. AB - The enormously risen and further increasing numbers of examinations and tests in microbiological diagnostics within the last years need new methods for treatment. One possibility to meet the higher requirements for information of the clinic without loss in quality at constant staff is the integration of the microcomputer technique into the laboratory as direct "tool". Demands for a qualitatively high empirical antimicrobial chemotherapy, chemotherapy according to antibiotic susceptibility tests, indicated use of antimicrobial drugs and control measures of infectious processes in general are met only by means of a fast information processing. The microcomputer technique in the laboratory provides also the chance to automate still manually performed tests and comprises according to algorithm the strict observation of the diagnostic process and its control. The application of the microcomputer technique on the one hand means for the technical assistant the omission of much manually performed work, on the other hand enables work of higher quality and supports decisions in the diagnostic process. Mathematical and statistical calculations are no longer connected with great losses of activity. The actual need for information of the clinician is met in time in different ways. PMID- 2193465 TI - [Possibilities and limits of pharmacotherapy of chronic venous insufficiency]. AB - The conservative therapy of the chronic venous insufficiency is always carried out with etiopathogenetic orientation and according to the stages of disease. Of the medicamentous therapy oedema-protective and vein-tonicising drugs, oral anticoagulants and non-steroidal antiphlogistics are discussed. Furthermore, the alternative and supplementary prescription of physiotherapy and movement cure depending on findings is dealt with. PMID- 2193466 TI - [Expert assessment of chronic venous insufficiency]. AB - In the expertise of a chronic venous insufficiency kind and stage of the venous disease must be proved as objectively as possible. The diagnostic demands in the individual step programmes serve for the exact assessment of the remaining part of efficiency. The criteria of valuation are summarized, in which case we also deal with several possibilities of combination with other vascular diseases. The expert opinion of an accident is discussed. References to the inability to work, rating of nursing money, increased material benefit in impairments of health and to the acknowledgement of an identity card for injured persons supplement the statements. PMID- 2193467 TI - [Urokinetography in the diagnosis and follow-up of obstructive uropathy in children]. AB - With regard to different paediatric urological diseases nuclear-medical urokinetography using the tracer 99m-Tc-DTPA can identify typical functional patterns. By means of 261 investigations on 240 children, retroperistaltic waves, initial pyeloureteral and the final ureterovesical conus, dysperistaltic waves and interrupting empty strips with lacing, constrictive peristalsis can be shown in comparison with the normal anterograde "stair" pattern. Moreover, UKG as a functional method makes it possible to control the therapeutic success of antibiotics in urinary inflammations, the situation after stone discharges and application of vegetative systemic drugs. In our opinion the operative procedure and the prognosis of megaureters can be assessed. Consequently urokinetography is among the important preoperative investigations in paediatric urology and in the follow-up programme after reconstructive urological operations. Nuclear-medical isotope investigation is without significant risk and yields many diagnostic details. The method can be recommended for functional urological diagnosis in children or teenagers with high frequency of follow-up investigations or in patients with contrast medium allergy. Finally, ureter physiology can be checked in patients subjected to bone scintigraphy. Clinical research is possible via UKG without additional radiation exposure. PMID- 2193468 TI - Course of pregnancy, family history and genetics in children with spina bifida. AB - Course of pregnancy, family history and genetics were evaluated in 257 children with spina bifida and compared with 537 non-malformed controls investigated under the same criteria. Birth data exhibited a significant seasonality with a maximum in January and a minimum in July which differed from the average distribution of birth data in Bavaria (maximum April, minimum October). The total number of pregnancy disturbances was 60.6% in mothers of spina bifida children, whereas this figure amounted to 30.1% in mothers of the control group. This high incidence of pregnancy disturbances in spina bifida was due to a high rate of diseases (6 times above controls) and drugs (6 times above controls) during early pregnancy. In 22.9% of children with spina bifida malformed relatives were found, whereas this was the case in only 6.4% of the children of the non-malformed control group. Not only malformations of the central nervous system but also malformations of other organ systems were found to be increased in relatives. This is a pointer not only to genetic influences as well-known aetiological factor, but also towards a generally higher susceptibility to malformation genesis in a relatively small group of persons. Risk of recurrence was 0.5% if one parent was affected and 4% if a sibling was affected. PMID- 2193469 TI - [Tracheal instability in tracheo-esophageal abnormalities]. AB - The clinical pattern of signs and symptoms of respiratory complications due to flaccid trachea has been analysed in 83 children treated in our hospital between 1983 and 1988 for tracheo-oesophageal malformations. These signs and symptoms are classified according to endoscopic findings, and are thus arranged according to various degrees of severity. Of the surviving children who were followed up and who were suffering from oesophageal atresia Vogt III B, only 5 of 57 were without a pointer towards flaccid trachea, whereas in oesophageal atresia Vogt II there were two of three. The two children with an isolated tracheo-oesophageal fistula showed abnormal findings both clinically and via endoscopy. 16 of the 20 children with very severely pronounced flaccid trachea--defined by the occurrence of life threating apnoeas and an endoscopically identifiable tracheal collapse of more than two-thirds of the lumen--were subjected to surgery via aortosternopexy. A marked and identifiable improvement was obtained in 15 cases. Complications caused by surgery consisted of temporary phrenicus lesions in two cases. PMID- 2193470 TI - [Tracheal compression by the brachiocephalic trunk in infants--surgical treatment of 30 cases]. AB - This is a report on 30 cases of innominate artery compression of the trachea and its operative correction by an aorto-truncopexy. Tracheoscopy is the most important examination for arriving at the diagnosis. Magnetic resonance imaging (MRI), which offers representative pictures of many moments of expiration and inspiration, shows the anatomic relationship between the innominate artery, the aortic arch and the trachea, also demonstrating the extent of the tracheal compression. Surgical treatment is indicated if narrowing of the lumen of the trachea is greater than 70%. By fixing the aortic arch and the proximal innominate artery at the back of the sternum the trachea is relieved of its compression. In 30 children there was no unsuccessful operation, and none of them died. PMID- 2193471 TI - [Perforated gastroduodenal ulcer. I. postoperative mortality and late results following simple suturing]. AB - Following the introduction of H2-blockers in the treatment of gastroduodenal ulcer disease, there has not been a change in the incidence of perforated peptic ulcer. By the diagnosis of perforated peptic ulcer the indication for an emergency operation is shown in generally. The postoperative mortality amount now as before 10% and the ulcer relapse rate behave less or more high, dependent on operative procedures, which optical choice is open. Therefore the perforated gastroduodenal ulcer has not lost any actuality. The following paper takes into account the informations of 245 patients from 1970 to 1988, which perforation of peptic ulcer were treated only with simple suture. The collection of data was retrospective till 1985 and since then prospective. Beside analysis of postoperative mortality, reasons of death, complications during healing and preoperative false diagnosis we have done a follow up of operated patients till 1987 (n = 232). On the basis of the results a statement was given for the therapeutical management of ulcer perforations. PMID- 2193472 TI - [Surgical heritage. The first 50 years of modern surgery. Sauerbruch memorial address, 17th Congress of the Association for Surgery in the DDR, 3-13-1989]. PMID- 2193473 TI - [The postnatal ontogeny of gonadal endocrine function in the water vole Arvicola terrestris with differing coat colors]. PMID- 2193474 TI - Quantitative surface electromyography (qEMG): applications in anaesthesiology and critical care. AB - During general anaesthesia and in lowered vigilance states such as after major trauma and during heavy sedation or analgesic medication, patients' ability to communicate with their surroundings is limited. Subjective intuitional interpretation may be the only means to ascertain a patient's emotional state, mood, and pain perception. Electromyographic detection and quantification of minimal and covert facial mimic muscle activity in anaesthesiology and critical care was an interesting concept worth further evaluation. In this study, the behaviour of quantitative surface-detected electromyographic activity (qEMG) was investigated during common anaesthetic events, post-operatively, and in volunteers as well as in experimental animals. A review of the methodology includes the necessary details for reproduction of the studies, including computerized processing of numerical data available in the commercial equipment. Results from the monitoring of 218 patients, seven volunteers and 31 rats are discussed. Conclusions are based on 32 testable null-hypotheses, the earlier documented literature and the author's own experience. The qEMG signal was derived from two electrodes placed on the frontal area and on the mastoid process behind the ipsilateral ear. After amplification, the signal was filtered to obtain a portion containing electrical activity between 60-300 Hz, which was considered to represent electromyographic activity. The signals were thereafter full-wave rectified and averaged with a 1-s time constant. The output of the processing unit consisted of a graphics display and a numeric computer output. A variety of clinical conditions and drug effects were studied in order to evaluate the method's applicability in research and in routine anaesthetic practice. The facial muscles turned out to be less sensitive to the effects of neuromuscular blocking drugs than the hand muscles, the normal monitoring site of neuromuscular transmission. Although muscle relaxants had a suppressing effect on spontaneous EMG activity, they did not abolish the ability of facial muscles to react to noxious stimuli. Also abdominal muscles retained this capability, though presumably through a different motor mechanism. Depolarizing and non-depolarizing neuromuscular blocking drugs had disparate effects on spontaneous EMG activity; succinylcholine seemed to facilitate the qEMG amplitude during recovery of the block. Quantitative surface electromyography revealed impending arousals during lightening anaesthesia, although this was not a consistent phenomenon. Inadequate anaesthesia was always reflected by an increase in facial qEMG, albeit this often was also evident to the naked eye. The arousal at the end of anaesthesia was always associated with an abrupt increase in facial qEMG activity, which often was preceded by a more gradual, predictive rise. Auditory stimulation was also effective in increasing qEMG.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2193475 TI - The influence of ketanserin on blood pressure and heart rate during induction of anesthesia: a randomized double blind controlled evaluation. AB - Increases in blood pressure and heart rate often seen with laryngoscopy and endotracheal intubation during induction of anesthesia can be dangerous for many patients. In twenty five patients pretreated with ketanserin, a new antihypertensive agent, changes in blood pressure and heart rate were compared with the hemodynamic parameters of twenty untreated patients. Ketanserin 10 mg intravenously was administered prior to induction of anesthesia. Ten mg i.v. ketanserin will not prevent increases in arterial pressure; however the increases in diastolic and mean arterial pressure are significantly lower than these increases in untreated patients. PMID- 2193476 TI - Predictive value of quantitative cisternography in normal pressure hydrocephalus. AB - Twenty-five patients with normal pressure hydrocephalus (NPH) and 16 patients with cerebral atrophy were investigated by quantitative cisternography using anterior images of the head 3, 6 and 24 h after a lumbar injection of 200 MBq 99mTc DTPA (diethylene-triamine-penta-acetic acid). The activity in the lateral ventricles, basal cisterns, hemispheric convexities and total intracranial region was measured. Ratios between these regions/quantities were calculated. Fifteen of the NPH patients improved while 10 were unchanged after ventriculo-peritoneal shunt surgery. The ratio between ventricular and total intracranial activity (V/T) correlated positively with the degree of improvement after shunt surgery. All NPH patients with a V/T ratio higher than 32% improved after the operation but a V/T ratio less than 32% did not exclude the possibility of improvement. With regard to quantitative measurements, the radionuclide cisternography procedure can be reduced to imaging at 24 h. PMID- 2193477 TI - Antibiotic prophylaxis in surgery for hip fractures. AB - Totally, 185 patients, operated on for a fresh hip fracture, were randomly allocated to either methicillin antibiotic prophylaxis or no prophylaxis and followed for 1 month. Two superficial wound infections were recorded in the prophylaxis group and one in the control group. Prophylactic use of antibiotics in surgery for hip fractures seems unnecessary provided strict aseptic routines in the operating room are followed. PMID- 2193478 TI - Hip arthroplasty infection. Current concepts. AB - Due to systemic or local antibiotic treatment and other preventive procedures, the incidence of deep hip-prosthetic infections in Scandinavia is less than 1 percent, with the majority hematogenous. Coagulase-negative staphylococci and anaerobes are involved in more than half of the cases. The diagnosis is sometimes difficult; preoperative aspiration often gives misleading results; and granulocyte scanning usually adds valuable information. In deep infection the current strategy is to revise with a two-stage procedure. Revisions should be carried out at specialized centers with bacteriologic competence and sufficient experience with implants. PMID- 2193479 TI - Transmission electron microscopy of bone tissue. A review. PMID- 2193480 TI - Chromosomal evolution and tumor progression in a myxoid liposarcoma. AB - A myxoid liposarcoma showed macroscopic, histologic, and cytogenetic heterogeneity. In one of three myxoid nodules and in the surrounding lipoma-like tumor tissue, the translocation t(12;16)(q13;p11), known to be specific for myxoid liposarcoma, was found as the sole chromosomal abnormality. In the other two nodules, additional rearrangements involving chromosomes 1, 12, and 16 were found. These aberrations were probably secondary to the primary t(12;16), and are cytogenetic evidence of clonal evolution. The complex chromosome aberrations were present in those tumor parts that had more malignant histology, indicating that the acquisition of secondary chromosomal aberrations parallels the histologic manifestations of tumor progression. PMID- 2193481 TI - Abduction treatment in late diagnosed congenital dislocation of the hip. Follow up of 1,010 hips treated with the Frejka pillow 1967-76. AB - There are many countries such as Poland where treatment of congenital hip dislocation is started late. The purpose of this work was to report our results in this group of children. 1010 hips in 780 children with congenital dislocation of the hip were treated with the Frejka pillow. The early results were evaluated in 830 hips at 15-36 months of age and the late results in 527 hips at a mean age of 14 (10-21) years. 90 percent of the children were treated by the same physician. The age at the onset of the treatment varied from 2 weeks to 24 months, with 12 percent younger than 3 months and 28 percent older than 6 months. The initial degree of dislocation was determined with our own index. Radiographic results were evaluated with a scoring based on four or six parameters. There were 6 percent failures, including lack of reduction or redislocation at the time when the child started to walk. Ischemic necrosis was observed in 14 percent of the hips, with significant permanent sequelae in 5 percent. Indications for surgical treatment of residual dysplasia were found in 4 percent of the hips evaluated early; and in the group evaluated late, still 5 percent of the hips required operation. There was good ability for spontaneous remodeling between the age of 3 and 7 years, whereas around the age of 10, the radiographic appearance of the hip became stabilized. At the end of treatment and at the time when the children started to walk, 59 percent of the early evaluated hips were still insufficiently remodeled; but in cases evaluated late, 95 percent of them had a normal or almost normal radiographic appearance. At that time, the clinical state of the children was satisfactory. The results of treatment depended on the initial degree of displacement. Only when treatment was begun after 5 months of age did the patient's age affect the treatment results. The Frejka pillow successfully reduced and stabilized these hips. PMID- 2193482 TI - The pathogenesis and treatment of cholesteatoma. AB - Congenital cholesteatoma, which arises from embryonic epidermoid tissue, is rare. In the majority of cases the cholesteatoma is acquired. It may develop as a retraction pocket involving the whole membrane, as a result of migration over the perforation edges or as basal cell invasion behind an intact membrane. There is no evidence for a metaplastic process or a Langerhans' cell mediated origin. Treatment modalities include several methods of either conservative or radical surgery, the main aim being one-stage total eradication of cholesteatoma and simultaneous reconstruction. With appropriate surgical methods recurrence figures after 5 years should remain under 10%. The patient's own tissues are the material of choice in the reconstruction. PMID- 2193483 TI - Nose/mouth distribution of respiratory airflow in 'mouth breathing' children. AB - Oro-nasal distribution of respiratory airflow was determined in 120 'mouth breathing' children by a minimally invasive computer-assisted method that employed a modified CPAP nasal mask/pneumotach and a head-out body plethysmograph. Resulting measurements were reproducible but clinical assessments correlated poorly with these values. Airflow distribution was almost identical in inspiration and expiration. 100% nasal breathing was found over a wide range of nasal resistances, many subjects with lips apart. Overall, the nasal fraction was negatively correlated with resistance and it was increased by topical decongestant. Decreasing nasal resistance with increasing age was confirmed, but corresponding changes in airflow distribution were not demonstrated. Quantitative assessment is advocated in clinical management of 'mouth breathers'. PMID- 2193484 TI - Diffuse sclerosing variant of papillary carcinoma of the thyroid. A histopathological study of four cases. AB - We present four cases of an unusual diffuse sclerosing variant of papillary carcinoma of the thyroid occurring in Japanese women ranging in age from 17 to 42 years. Macroscopically, both lobes of the thyroid were involved, being diffusely enlarged and firm. Histologically, the tumor was characterized by squamous metaplasia of tumor cells, numerous psammoma bodies, extensive stromal fibrosis, severe lymphocytic infiltration with formation of lymph follicles, and thin bundles of smooth muscle cells in the fibrous stroma. The tumor islands were located mainly within the dilated lymphatic vessels and the metastatic tumor involved the bilateral cervical lymph nodes in all cases. It is assumed that papillary carcinoma of this type invades the thyroid lymphatics during the early stage and, without forming nodular lesions, disseminates to both lobes with extensive metastasis to the cervical lymph nodes. It should be noted that papillary carcinoma of this type often suggests chronic thyroiditis clinically because of the symmetrical enlargement of the thyroid and frequent positive anti thyroid antibodies in the serum. Some workers have reported the prognosis to be unfavorable because of extensive lymphatic involvement, but the prognosis of this variant has not yet been defined. PMID- 2193485 TI - Malignant schwannoma arising in the intracranial trigeminal nerve. A report of an autopsy case and a review of the literature. AB - An autopsy case of malignant schwannoma arising in the intracranial trigeminal nerve is reported. The tumor involved the right cerebellopontine angle of the brain stem in an 18-year-old man. The spindle-shaped tumor cells with eosinophilic cytoplasm proliferated in fascicles and exhibited hypercellularity, pleomorphism, increased mitotic activity and invasive growth. Ultrastructurally, interdigitating cytoplasmic processes and a few fragmented basal lamina-like structures were observed. Immunohistochemically, some tumor cells were reactive with conventional anti-S-100 protein antibody, but negative for beta subunit. Most tumor cells were positive for alpha subunit of S-100 protein. This is the eighth reported case of malignant schwannoma arising in the intracranial trigeminal nerve. PMID- 2193486 TI - [The physiopathology of supranuclear structures in oculomotor disorders]. AB - Several structures, located at different levels in the Central Nervous System (CNS), collaborate to the control and realization of ocular movements (O.M.) Therefore, alterations of oculomotricity, of varying degree and of different kinds, may be found in a lot of diseases of the CNS. The study of O.M., expecially when carried out by means of specific techniques such as electro oculography, may represent an useful tool in the diagnosis (both from a topographic and an etiological standpoint) and in the follow-up of patients, possibly also allowing a precise evaluation of therapy effectiveness. In this review the Authors briefly examine the role of the supranuclear structures mostly involved in the control and in the execution of oculomotricity and the characteristics of the different types of O.M. (rapid and slow, vergence movements). Successively, they analyze the semeiological features of supra nuclear disturbances of O.M., describing alterations of saccadic movements (slowing, dysmetria) and of smooth pursuit, fixation instability (square waves, flutter, opsoclonus, nystagmus,...) and other alterations of O.M. (ocular bobbing, see-saw nystagmus, skew deviation,...). Successively, disturbances of O.M. are analyzed in relation to their topodiagnostic significance, describing oculomotor involvements due to focal lesions of different areas of CNS (frontal cortex, parieto-occipital cortex, basal ganglia, cerebellum, brainstem) and particular syndromes (Foville syndromes, locked-in syndrome, Parinaud syndrome, anterior internuclear ophthalmoplegia, "one and a half" syndrome, Balint syndrome,...). Finally, particular attention is drawn to the oculomotor disturbances observed in degenerative cerebellar and multisystemic diseases, and several abnormal "oculomotor patterns", which seem to be specifically related to particular diseases, are described. In particular, the oculomotor patterns of Steele-Richardson-Olszewsky disease (slowing and hypometria of horizontal saccades, loss of upward saccades with preservation of reflex movements) and of Friedreich ataxia (fixation instability mostly due to the occurrence of square waves, saccadic dysmetria, impairment of smooth pursuit) are stressed. PMID- 2193487 TI - The lethal osteochondrodysplasias. PMID- 2193488 TI - Mutations in type I procollagen genes that cause osteogenesis imperfecta. PMID- 2193489 TI - Structural defects in inherited and giant platelet disorders. AB - As diverse as the group of inherited structural defects and giant platelet disorders presented in this chapter may seem, there is a common thread that ties them together. All appear to represent some form of membrane aberration. Sometimes only a small inclusion identifies the membrane defect, sometimes a massive increase in size. In others, whole populations of organelles are missing or surface membranes lack specific glycoproteins essential for their function. All of them are born in the deep recesses of a hidden cell, the bone marrow megakaryocyte. Getting the megakaryocyte out into the light of day, or at least into a culture medium, should certainly lead to the solution of many, if not all, of the disorders of platelet membranes and membrane disorders. We have not been completely successful in our efforts to study the megakaryocyte in vitro. As a result, we do not yet understand the normal megakaryocyte, much less normal platelet. The megakaryocyte presents one of the greatest of challenges to our understanding of membrane biology. As our knowledge of how its cytoplasm fills with interiorly and exteriorly derived membranes, and the mechanisms underlying their organization into platelet surfaces, channels of the OCS and DTS, membrane complexes, and five kinds of organelles become clear, our ability to define the basic nature and inheritance of defects will improve rapidly. Within the next decade most aspects of platelet molecular genetics and cell biology will be solved. PMID- 2193490 TI - Genetic aspects of immunoglobulin A deficiency. AB - IgA deficiency is one of the most common of all immune defects. While it is often not associated with clinical illness, presumably due to compensation from other sectors of the immune system, IgA-deficient individuals are distinctly more likely to become ill and have one or more of specific groups of diseases. While the unifying immunologic perturbation in IgA deficiency is a lack of mature IgA secreting B cells, a host of other, usually minor, immunologic abnormalities have been reported in such patients. IgA deficiency can be inherited in an autosomal dominant or autosomal recessive fashion, but most individuals who are IgA deficient have no other affected family members. From a genetic point of view, IgA deficiency has been associated with three chromosomes, 18, 14, and 6. Many IgA-deficient individuals who have cytogenically detectable abnormalities of chromosome 18 have been reported, but all the individuals with these defects have severe congenital defects of other kinds. Obscuring the relationship between chromosome 18 and IgA deficiency is the fact that both short- and long-arm deletions have been reported in IgA deficiency. The chromosome deletions in the individuals who are IgA deficient thus appear to have no common pattern. While a rare individual can be IgA1 deficient on the basis of heavy-chain deletions of alpha 1 genes in concert with other heavy-chain genes on chromosome 14, such individuals are quite rare, and from a clinical point of view, those reported have usually been healthy. Absence of both IgA1 and IgA2 genes (presumably in concert with other heavy-chain genes) has never been reported. For chromosome 6, a more complex puzzle emerges. IgA-deficient individuals have been reported to have one of a few specific HLA haplotypes. While many individuals with these supratypes are not IgA deficient, these findings encourage the notion that the secretion of IgA could be at least partly controlled by genes residing in the major histocompatibility locus. PMID- 2193491 TI - Oxidative phosphorylation diseases. Disorders of two genomes. PMID- 2193492 TI - Successful multiple segment coronary angioplasty: effect of completeness of revascularization in single-vessel multilesions and multivessels. AB - A long-term follow-up study was performed to evaluate the long-term value of performing multiple dilatations according to their procedural (single-vessel multilesion or mutltivessel dilatations) and anatomic types (single-vessel disease with multiple dilatations or multivessel disease dilatations with complete and incomplete revascularization). From 1980 until 1988, 248 patients met the following criteria: (1) at least two lesions dilated (range: 2 to 4) and (2) all attempted lesions successfully dilated. The mean length of follow-up was 33 months. The end points analyzed were death, myocardial infarction, redilatation, and bypass surgery. No differences were found for these events between the single-vessel multilesion group (144 patients) and the multivessel group (104 patients). The 4.5-year probability of event-free survival was 68% and 70%, respectively, for the multilesion group and the multivessel group. In the event-free patients, 57% versus 59% were asymptomatic and 45% versus 46% were not taking antianginal drugs. In the anatomic subgroups, there were less event-free patients in the cohort of incompletely revascularized multivessel disease patients (55% of 55 patients) when compared with the cohort of those who were completely revascularized (84% of 79 patients) or when compared with the single vessel disease multiple dilatation patients (74% of 107 patients). The 4.5-year event-free survival probability for each group was 44%, 78%, and 74%, respectively. This difference was caused by more infarctions (9% versus 2% versus 4%, respectively) and bypass operations in the multivessel disease, incomplete revascularization group (20% versus 5% versus 10%, respectively). In event-free patients, improvement of angina was similar and was documented in over 85% of patients in each group. Furthermore, the number of asymptomatic patients at follow-up was similar in all groups except that within the incomplete revascularization group, less patients were free of antianginal drugs (21% versus 51% versus 48%). Finally, 48% of the entire cohort performed an exercise test 4.6 months (mean) after dilatation and no difference was found in any of the variables in any group. About 10% of the patients experienced angina and approximately 30% had a positive exercise test for ischemia by ST segment criteria. The functional performance in every group was over 90% of the predicted work load. These results suggest that completeness of revascularization in multivessel disease patients is an important prognostic variable. However, the symptomatic improvement after dilatation is very rewarding in all subsets of patients and argues in favor of the continued use of multiple dilatations as a treatment strategy. PMID- 2193493 TI - The effects of clonidine hydrochloride versus atenolol monotherapy on serum lipids, lipid subfractions, and apolipoproteins in mild hypertension. AB - The study objective was to determine the effects of monotherapy with clonidine and atenolol versus placebo on serum lipids, apolipoproteins, and blood pressure in patients with mild primary hypertension. The protocol comprised a double blind, randomized, placebo-controlled 5-month prospective study carried out in an outpatient general internal medicine clinic in a university medical center. There were 92 patients ages 18 to 70, with mild primary hypertension (sitting diastolic blood pressure of greater than 90 mm Hg and less than 105 mm Hg) without significant cardiac, renal, cerebrovascular, hepatic, neoplastic, or hematologic disorders. Patients with severe hyperlipidemia or peripheral vascular disease were also excluded. All factors known to effect serum lipids were held constant throughout the study (i.e., diet, weight, exercise, caffeine, tobacco). Atenolol and clonidine significantly reduced blood pressure when compared with placebo. Atenolol caused significant increases in serum triglycerides and apolipoprotein B (p less than 0.05) and significant reductions in high-density lipoprotein cholesterol, apolipoproteins A-I and A-II (p less than 0.05). Atenolol also induced a significant adverse effect on all lipid ratios, increasing total cholesterol/high density lipoprotein-cholesterol, low density lipoprotein cholesterol/high density lipoprotein-cholesterol, apolipoprotein B/apolipoprotein A-I and apolipoprotein B/apolipoprotein A-II ratios and decreasing low density lipoprotein-cholesterol/apolipoprotein-B ratio (p less than 0.05). Clonidine caused significant reductions in high-density lipoprotein-cholesterol, apolipoproteins AI and AII (p less than 0.05 but was neutral on all other lipids, lipid subfractions, and apolipoproteins. Clonidine did not significantly alter any of the lipid ratios.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2193494 TI - Acute management of paroxysmal atrioventricular junctional reentrant supraventricular tachycardia: pharmacologic strategies. AB - A vast array of effective antiarrhythmic agents offers the attending physician attractive options for termination of PJRT. Calcium channel blockers, adenosine compounds, amjaline, and the newer drugs flecainide and propafenone offer an efficacy rate of more than 80% for acute termination of PJRT. Choice should be based on the patient's clinical characteristics including any underlying cardiac or noncardiac pathologic conditions, hemodynamic status, and current medications. Drugs with a very short half-life (adenosine compounds) offer the possibility of repeated administration at increasing dosages or of subsequent administration of a second antiarrhythmic drug without fear of increased adverse effects or drug interactions. Drugs with a long half-life, such as calcium channel blockers, flecainide, and propafenone, have the potential advantage of preventing an immediate recurrence of the arrhythmia. Adenosine compounds are the fastest acting drugs, resulting in termination of PJRT in less than 30 seconds. The cardiac side effects of all antiarrhythmic drugs represent an exaggeration of their intrinsic electrophysiologic and hemodynamic effects. Thus hemodynamic decompensation and bradyarrhythmias resulting from sinus nodal, AV nodal, or infranodal dysfunction are of major concern. Side effects of adenosine compounds are extremely common but very short lasting. Verapamil is both highly effective and safe except in very special circumstances. Guidelines for therapy of PJRT in specific groups of patients are provided. PMID- 2193495 TI - Analysis of possible triggers of acute myocardial infarction (the MILIS study). AB - Recent documentation of a circadian variation in acute myocardial infarction (AMI) suggests that AMI is not a random event, but may frequently result from identifiable triggering activities. The possible triggers reported by 849 patients enrolled in the Multicenter Investigation of Limitation of Infarct Size were analyzed. Possible triggers were identified by 48.5% of the population; the most common were emotional upset (18.4%) and moderate physical activity (14.1%). Multiple possible triggers were reported by 13% of the population. Younger patients, men and those without diabetes mellitus were more likely to report a possible trigger than were older patients, women and those with diabetes. The likelihood of reporting a trigger was not affected by infarct size. This study suggests that potentially identifiable triggers may play an important role in AMI. Because potential triggering activities are common in persons with coronary artery disease, yet infrequently result in AMI, further studies are needed to identify (1) the circumstances in which a potential trigger may cause an event, (2) the specific nature of potential triggering activites, (3) the frequency of such activities in individuals who do not develop AMI and (4) the presence or absence of identifiable triggers in various subgroups of patients with infarction. PMID- 2193496 TI - Beneficial and detrimental effects of lidoflazine in microvascular angina. AB - Lidoflazine, a piperazine derivative calcium antagonist, was investigated as therapy in 22 patients with microvascular angina (chest pain, angiographically normal coronary arteries and left ventricle, microvascular constrictor response to pacing after ergonovine administration and limited coronary flow response to dipyridamole). Eighteen of 22 patients reported symptom benefit while taking lidoflazine 360 mg daily. Compared to baseline exercise treadmill testing, lidoflazine resulted in significant improvement in exercise duration (812 +/- 337 vs 628 +/- 357 seconds, p less than 0.01) and time to onset of chest pain (530 +/ 343 vs 348 +/- 246 seconds, p less than 0.01). The 5 patients with ischemic ST segment changes during baseline testing demonstrated an almost 4-minute delay in ST-segment depression (3 patients) or no ST-segment depression (2 patients) while taking lidoflazine. Repeat invasive study of coronary flow in 11 patients taking lidoflazine demonstrated significantly greater coronary vasodilation at rest, during pacing, during pacing after ergonovine and after dipyridamole administration (all p less than 0.03), compared to the initial drug-free study. During the randomized, placebo-controlled phase of the study with 7-week treatment periods, 9 of 11 patients who completed this phase of the study preferred lidoflazine and all demonstrated improved exercise capacity with lidoflazine compared to placebo. However, 3 patients developed malignant ventricular arrhythmias, and 1 died while taking lidoflazine, resulting in termination of the study. Limited coronary vasodilator response in microvascular angina has a reversible vasoconstrictor component and may be due to elevated systolic calcium levels. Despite the hemodynamic, symptom and exercise benefit, lidoflazine may be unsafe for clinical use because of its propensity to cause potentially fatal ventricular arrhythmias. PMID- 2193497 TI - Biobehavioral variables and mortality or cardiac arrest in the Cardiac Arrhythmia Pilot Study (CAPS). AB - The frequency of ventricular premature complexes and the degree of impairment of left ventricular ejection fraction are major predictors of cardiac mortality and sudden death in the year after acute myocardial infarction. Recent studies have implicated psychosocial factors, including depression, the interaction of social isolation and life stress, and type A-B behavior pattern, as predictors of cardiac events, controlling for known parameters of disease severity. However, results tend not to be consistent and are sometimes contradictory. The present investigation was designed to test the predictive association between biobehavioral factors and clinical cardiac events. This evaluation occurred in the context of a prospective clinical trial, the Cardiac Arrhythmia Pilot Study (CAPS). Five-hundred two patients were recruited with greater than or equal to 10 ventricular premature complexes/hour or greater than or equal to 5 episodes of nonsustained ventricular tachycardia, recorded 6 to 60 days after a myocardial infarction. Baseline behavioral studies, conducted in approximately 66% of patients, included psychosocial questionnaires of anxiety, depression, social desirability and support, and type A-B behavior pattern. In addition, blood pressure and pulse rate reactivity to a portable videogame was assessed. The primary outcome was scored on the basis of mortality or cardiac arrest. Results indicated that the type B behavior pattern, higher levels of depression and lower pulse rate reactivity to challenge were significant risk factors for death or cardiac arrest, after adjusting statistically for a set of known clinical predictors of disease severity. The implication of these results for future research relating behavioral factors to cardiac endpoints is discussed. PMID- 2193498 TI - Antiarrhythmic and hemodynamic evaluation of indecainide and procainamide in nonsustained ventricular tachycardia. AB - The present trial was a placebo-controlled, randomized, parallel study comparing indecainide to procainamide. A 24-hour intravenous phase measured and compared invasive hemodynamics, followed by oral administration for assessment of arrhythmia suppression. Thirty-two patients (mean age 61 years) with asymptomatic or mildly symptomatic nonsustained ventricular tachycardia (VT) were evaluated, 15 while receiving indecainide and 17 while receiving procainamide. A total of 8 patients had serious toxicity during the intravenous phase; 6 receiving indecainide experienced increased left ventricular dysfunction or worsening arrhythmia (sustained VT, arrhythmic death) while 2 receiving procainamide developed serious hypotension. Proarrhythmia developed in 3 of 15 (20%) of the indecainide patients, but in no procainamide patient. In those tolerating indecainide, long-term suppression of ventricular premature complexes (VPCs) and of runs of VT was more consistent than with procainamide. While indecainide was a potent suppressor of spontaneous VPCs and VT, patients with significant left ventricular dysfunction could not tolerate it. The indecainide patients developing serious toxicity had a common hemodynamic profile: ejection fraction less than 25%, elevated left ventricular filling pressures, low cardiac and stroke volume index and minimal cardiac reserve. Indecainide has a poor risk benefit ratio in patients similar to the current population, who have potentially lethal ventricular arrhythmias and severe left ventricular dysfunction. PMID- 2193499 TI - Relation of thrombolysis during acute myocardial infarction to left ventricular function and mortality. PMID- 2193500 TI - Dietary n-3 polyunsaturated fatty acids and amelioration of cardiovascular disease: possible mechanisms. AB - Consumption of n-3 polyunsaturated fatty acids (n-3 PUFAs) is associated with a reduced incidence of coronary arterial diseases. Dietary n-3 PUFAs act via several mechanisms. They depress plasma lipids, especially triglycerides (TGs), by inhibiting hepatic TGs and possibly apoprotein synthesis. They replace arachidonic acid (AA) in phospholipid pools with eicosapentaenoic acid (EPA) and docosahexaenoic acids (DHA). EPA and DHA, when released, inhibit cyclooxygenase and lipoxygenase and reduce eicosanoid synthesis, particularly thromboxane (TXA2) and leukotriene B4 (LTB4), by platelets and macrophages. Reduction of the proaggregatory, vasoconstrictive TXA2 decreases the thrombotic tendency of platelets. This is augmented by the limited depression of the vasoactive antiaggregatory prostacyclin (PGI2) and the generation of antiaggregatory prostaglandin I3 (PGI3) from EPA. The n-3 PUFAs also depress eicosanoid metabolism in platelets, monocytes, and macrophages, and thereby may retard the initiation and progress of atherogenesis. n-3 PUFAs reduce blood pressure and blood viscosity and modulate membrane fluidity and associated enzyme and receptor functions. The collective effects of n-3 PUFAs may account for the reduction in coronary arterial disease in populations consuming foods containing n-3 PUFAs. PMID- 2193501 TI - Simultaneous measurement of free-living energy expenditure by the doubly labeled water method and heart-rate monitoring. AB - Total energy expenditure (TEE) was measured simultaneously in 14 free-living adults over 15 d by the doubly labeled water (DLW) method and for 2-4 separate days by heart-rate (HR) monitoring. Individual curves for HR vs oxygen consumption (VO2) were obtained and an HR (FLEX HR: 97 +/- 8 beats/min, range 84 113 beats/min) that discriminated between rest and activity was identified. Calibration curves were used to assign an energy value to daytime HR above FLEX HR. Below FLEX HR energy expenditure was taken as resting metabolism. Sleeping energy expenditure was assumed to be equal to basal metabolic rate. Average HR TEE (12.99 +/- 3.83 MJ/d) and average DLW TEE (12.89 +/- 3.80 MJ/d) were similar. HR TEE discrepancies ranged from -22.2% to +52.1%, with nine values lying within +/- 10% of DLW TEE estimates. The FLEX HR method provides a close estimation of the TEE of population groups. However, an increased number of sampling days may improve the precision of individual estimates of TEE. PMID- 2193502 TI - Comparison of doubly labeled water, intake-balance, and direct- and indirect calorimetry methods for measuring energy expenditure in adult men. AB - Energy expenditure (EE) of four adult men on a weight-maintenance diet was estimated by use of doubly labeled water, intake balance, and direct and indirect calorimetry. The doubly labeled water (2H218O) method was used to estimate free living EE for 13 d. Metabolizable energy (ME) intake was used to estimate free living EE for 1 wk. The subjects' 24-h EE was measured in a dual direct-indirect room calorimeter on 3 alternate days. Estimates of free-living EE as measured by ME intake and doubly labeled water indicate agreement between the two methods (mean difference +/- SEM, -1.04 +/- 0.63%). Measurements of EE with indirect and direct calorimetry are equivalent (mean difference 0.63 +/- 0.44%). The daily EE measured by doubly labeled water in these free-living adults over a 13-d period was 15.01% greater than the 24-h EE measured within the calorimeter. PMID- 2193503 TI - Protein turnover and thermogenesis in response to high-protein and high carbohydrate feeding in men. AB - The rates of energy expenditure and wholebody protein turnover were determined during a 9-h period in a group of seven men while they received hourly isocaloric meals of high-protein (HP) or high-carbohydrate (HC) content. Their responses to feeding were compared with those to a short period of fasting (15-24 h). The 9-h thermic response to the repeated feeding of HP meals was found to be greater than that to the HC meals (9.6 +/- 0.6% vs 5.7 +/- 0.4% of the energy intake, respectively, means +/- SEM, p less than 0.01). The rate of whole-body nitrogen turnover over 9 h increased from 17.6 +/- 2.2 g on the fasting day to 27.4 +/- 1.4 g during HC feeding (NS) and there was a further increase to 58.2 +/- 5.3 g resulting from HP feeding (p less than 0.001). By using theoretical estimates (based upon ATP requirements) of the metabolic cost of protein synthesis, 36 +/- 9% of the thermic response to HC feeding and 68 +/- 3% of the response to HP feeding could be accounted for by the increases in protein synthesis compared with the fasting state. PMID- 2193504 TI - Autoimmune cytopenias in Castleman's disease. AB - The authors report a case of Castleman's disease in which the major clinical problems have been caused by severe thrombocytopenia and neutropenia. The cytopenias were caused by autoimmune destruction of mature cells as demonstrated by bone marrow findings and cell-specific antibody assays. There also was evidence of red cell autoantibody production but no overt hemolysis. The thrombocytopenia currently is controlled by intermittent vincristine, having proved refractory to steroids, splenectomy, and danazol and only partially responsive to high dose intravenous immunoglobulin. The neutropenia showed temporary improvement with immunoglobulin but has been resistant to all other therapy. This case provides further evidence for disordered immune regulation in Castleman's disease. PMID- 2193505 TI - The identification of a rabbit-transmitted cervical toxoplasmosis mimicking malignant lymphoma. AB - A case is presented of acquired cervical toxoplasmosis occurring in a 43-year-old male, which clinically mimicked malignant lymphoma. The histopathology of this case was probable toxoplasmic lymphadenitis. Serologic tests and the use of FITC labeled antibodies revealed high levels of specific IgG antibodies in the serum and toxoplasmic antigens in paraffin sections of the patient, respectively. During survey of the infection route, it was learned that the patient's pet rabbit and three other rabbits of the same family line had cervicofacial lumps. The pet rabbit had high levels of toxoplasmic antibodies. Immunofluorescence tests on the infraorbital lump also revealed Toxoplasma gondii. Therefore, it was concluded that in this case the rabbit had transmitted Toxoplasma to the patient. The authors know of no other reports of toxoplasmosis transmitted by or through rabbit to human. PMID- 2193506 TI - Misleading statement about serum ferritin. PMID- 2193507 TI - Nonneoplastic and nonhyperplastic thymus in myasthenia gravis. An immunohistochemical study with double immunoenzymatic labeling of basement membrane and cellular components. AB - Histologically normal thymus (type A) in patients with myasthenia gravis (MG) was immunohistochemically compared with hyperplastic MG thymus (type B) and normal non-MG thymus. In formalin-fixed, paraffin-embedded sections of ten type A, ten type B, and eight non-MG cases, the thymic epithelium and other cellular components were stained in conjunction with the basement membrane by a double immunoenzymatic method. This technique demonstrated a moderate architectural disturbance in type A thymus, with distended perivascular space (PVS), elongated medullary epithelium, and disrupted basement membrane. These changes were more prominent in type B thymus but were minimal to lacking in non-MG thymus. Compared with those in non-MG thymus, the myoid cells in MG thymuses of both types tended to cluster around the Hassall's corpuscles, with a slight decrease in number in type B but not in type A. B-lymphocytes were present in type B, type A, and non MG thymuses in that order of abundance; the cells were confined to the medullary parenchyma in the non-MG group but were numerous both in the PVS and medulla in the MG groups. T-lymphocytes were increased in the expanded PVS of type A and B MG thymuses. The number of interdigitating reticulum cells was similar in the three groups, but the cellular distribution was more dispersed in MG thymuses of both types. These findings, although previously described in type B thymus, have not been well recognized in type A thymus. They support the view that a common abnormality (presumably chronic thymitis), differing in degree only, underlies MG thymuses regardless of the presence of follicular hyperplasia. PMID- 2193508 TI - Detection of breast carcinoma cells in human bone marrow using fluorescence activated cell sorting and conventional cytology. AB - Flow cytometry has been compared with conventional cytology as a method for detecting breast carcinoma cells in human bone marrow. Breast cancer cells from patient effusion fluids or from established cell lines were mixed with normal human bone marrow at dilutions ranging from 1:10 to 1:100,000. Cells were labeled with five directly fluoresceinated murine monoclonal antibodies reactive against epithelial cell surface determinants of 42, 55, 72, 200, and more than 200 kD. Fluorescence of tumor cells within the mixtures was then analyzed with the use of a fluorescence-activated cell sorter. In multiple experiments, one tumor cell in 10,000 nucleated marrow cells could be detected by flow cytometry. In addition, a linear correlation was observed over approximately 3 logs between the number of tumor cells added and the number of tumor cells detected. In a double-blind study comparing flow cytometry and cytology, flow cytometric analysis detected one tumor cell among 10,000 marrow precursors in 14 of 15 instances, whereas standard cytologic methods detected similar tumor contamination in 9 of 15 instances. Neither technique used individually could detect one tumor cell in 100,000 bone marrow cells. Used in combination, however, flow cytometry and cytology could detect one breast cancer cell among 100,000 normal marrow progenitors. PMID- 2193509 TI - The risk of bacterial growth in units of blood that have warmed to more than 10 degrees C. AB - Most transfusion services discard unopened units of blood that have been returned to the blood bank more than 30 minutes after the issuance or have attained a temperature of more than 10 degrees C. The objective of this study was to learn the prevalence of bacterial growth, if any, in the units of blood that were exposed twice, for six hours each time, to room temperature during their refrigerated storage. All of the 396 units cultured were negative except one red cell unit that grew a Bacillus species, probably B. subtilis. Further studies suggested that the growth of B. subtilis was due to laboratory contamination. The authors concluded that more work is needed to study the bacterial growth and the effect on red cell enzymes in the units of blood that are exposed to room temperature for varying periods or are returned to the blood bank after 30 minutes of issuance. If no adverse effect is noted, the policy of not reissuing such units may need revision so that more units could be salvaged. PMID- 2193510 TI - T-cell lymphoma after heart transplantation. AB - A 26-year-old woman who had undergone orthotopic heart transplantation because of dilative cardiomyopathy received a triple-drug immunosuppressive regimen (cyclosporine A, azathioprine, and prednisolone). During her relatively frequent episodes of acute rejection, she was treated with methylprednisolone and repeated application of ATG. A short time before the patient's death, a fine-needle aspiration of the liver revealed the cytologic diagnosis of a malignant pleomorphic medium-size cell non-Hodgkin's lymphoma of a higher grade of malignancy. Immunosuppression was reduced, and the patient died in cardiogenic shock related to a histologically confirmed episode of severe acute rejection 264 days after the transplantation. On autopsy, the malignant lymphoma previously diagnosed by fine-needle aspiration cytology was found to be present in the liver as the only extranodal localization. The immunohistologic analysis of the immunophenotype specified the lymphomatous neoplasia as a T-cell lymphoma. The particular importance of this case is that it is, to our knowledge, the third case of proven T-cell lymphoma following organ grafting documented in the literature and the first case described in a cardiac allograft recipient. PMID- 2193511 TI - Prophylactic intrapartum amnioinfusion: a randomized clinical trial. AB - Amnioinfusion was performed in a prospective, randomized trial of 60 women in the latent phase of labor with oligohydramnios, as defined by an amniotic fluid index less than or equal to 5.0 cm. All fetuses were at least 37 weeks' gestational age, had normal baseline fetal heart rate variability, and no clinically significant fetal heart rate decelerations at the outset. Subjects in the amnioinfusion group (n = 30) were titrated to and maintained at an amniotic fluid index level greater than or equal to 8.0 cm throughout labor. In the group receiving amnioinfusion, significantly lower rates of meconium passage (p = 0.04), severe variable decelerations (p = 0.04), end-stage bradycardia (p = 0.05), and operative delivery for fetal distress (p = 0.002) occurred. Significantly higher umbilical arterial blood pH values were also noted in the infusion group (p = 0.02). We conclude that prophylactic intrapartum amnioinfusion is an important technique for the reduction of intrapartum morbidity. PMID- 2193512 TI - Ultrasonography-guided early amniocentesis in singleton pregnancies. AB - Between October 1, 1986, and September 30, 1987, 1721 amniocenteses were performed at the University of California, Davis, Medical Center. Of these procedures 527 (30.6%) were early amniocenteses. Medical records were reviewed for maternal age, amniocentesis indication, color of amniotic fluid, gestational age, frequency of needle insertion, complications of amniocentesis and delivery, results of prenatal testing, and pregnancy outcome. Complete follow-up data were available for 517 (98.1%). There were 10 miscarriages before 28 weeks' gestation (1.9%), one loss after 28 weeks (0.2%), and one stillbirth (0.2%), resulting in a total postprocedural loss rate of 2.3%. Miscarriage within 2 weeks of amniocentesis occurred in four subjects (0.8%). PMID- 2193513 TI - What is fetal distress? AB - Fetal distress is a widely used but poorly defined term. This confusion of definition compounds the difficulty of making an accurate diagnosis and initiating appropriate treatment. The fetus reacts at the onset of asphyxia with a remarkable series of responses, primarily a complexly regulated redistribution of blood flow that serves to limit the deleterious effects of oxygen limitation in vital organs. This enables the fetus to survive asphyxia intact unless the insult is profound or prolonged. The most common asphyxial stresses imposed on the fetus during labor are insufficiency of uterine blood flow, or insufficiency of umbilical blood flow, and occasionally decrease in uterine arterial oxygenation. Each of these stresses produces characteristic fetal heart rate patterns: late decelerations, variable decelerations, or prolonged bradycardia. There is strong evidence that the presence of normal fetal heart rate variability represents normal central nervous system integrity, including adequate oxygenation. A decrease or loss of variability in the presence of these patterns is a sign that the physiologic compensations are overwhelmed as a result of the severity of asphyxia. Knowledge of the fetal responses to asphyxia, together with the known evolution of fetal heart rate patterns during asphyxia, should allow a more accurate definition of the onset of unacceptable asphyxia, and more rational management and timing of intervention. PMID- 2193514 TI - The placenta in the litigation process. AB - The placenta accurately reflects many important prenatal events. It is therefore important that it be examined. This is especially useful in cases of possible future litigation, the "bad-baby cases." There is much experience now that pathologic findings in the placenta often have a decisive role in the accurate disposition of legal cases. This presentation describes the examination of the placenta and provides a brief review of the nature of placental lesions that most often impact cases of alleged malpractice. PMID- 2193515 TI - Prenatal diagnosis of intracerebellar hemorrhage: case report. AB - Evidence continues to accumulate that neurologic damage can occur during the antenatal period, unrelated to intrapartum events. We report a case in which intracerebellar hemorrhage was diagnosed by antepartum ultrasonographic examination. Correlation of fetal heart rate patterns, Apgar scores with neonatal course, and neuropathologic findings are presented. Medicolegal implications are discussed. PMID- 2193516 TI - The diagnostic efficacy of the umbilical arterial systolic/diastolic ratio as a screening tool: a prospective blinded study. AB - This prospective blinded study investigated the diagnostic efficacy of the umbilical arterial systolic/diastolic ratio performed at 34 to 36 weeks' gestation for identifying pregnancies at a high risk for adverse perinatal outcomes. A series of 350 consecutive singleton pregnancies were included in the study. A continuous-wave Doppler instrument with a 4 MHz transducer was used. The criteria for an abnormal perinatal outcome included intrauterine growth retardation, an Apgar score of less than 7 at 5 minutes, umbilical arterial pH at birth less than 7.20, presence of thick meconium, fetal distress in labor, and neonatal complications necessitating admission to the neonatal intensive care nursery. The analytic techniques included determination of the receiver operating characteristic curve, sensitivity, specificity, positive and negative predictive values, and the kappa index. The results demonstrated that although the cutoff value of 2.9 showed the maximum inherent discriminatory power, its diagnostic efficacy (sensitivity, 0.83; specificity, 0.87 positive predictive value, 0.74; negative predictive value, 0.92; and kappa index, 0.68) was not substantially different from that of the more common cutoff value of 3.0 (sensitivity, 0.79; specificity, 0.93; positive predictive value, 0.83; negative predictive value, 0.91; and kappa index, 0.73). Both values were rated good to excellent by the kappa index. The study also demonstrated that the systolic/diastolic ratio was a better predictor of general abnormal outcome than of the suboptimal fetal growth. PMID- 2193517 TI - Ultrasonography and external cephalic version at term. AB - Sixty-five patients with nonvertex presentations at term were evaluated by ultrasonography to determine which factors were associated with a successful external cephalic version. Amniotic fluid volume, placental localization, type of breech, position of the fetal spine, and whether the breech had descended were determined and analyzed by chi 2 analysis. Only a frank breech and an anteriorly located fetal spine were associated with a successful version. Four episodes of fetal bradycardia occurred, none requiring operative intervention. There were no episodes of maternal bleeding or dislodgement of the placenta. Fifty-eight percent of all breech presentations were converted and 62% were delivered vaginally. We conclude that ultrasonography is useful in the evaluation of patients with a nonvertex presentation at term and can be used to predict which patients are likely to undergo a successful external cephalic version. PMID- 2193518 TI - Randomized prospective trial comparing ultrasonography and pelvic examination for preterm labor surveillance. AB - This study was designed to compare the effectiveness of cervical assessment by either ultrasonography or bimanual pelvic examination in a program for preterm labor surveillance. Patients (n = 57) at risk for preterm birth were seen once a week for patient education, review of symptoms, and cervical evaluation. Cervical evaluation was assigned randomly to either ultrasonographic evaluation or pelvic examination. The groups did not differ in demographic or obstetric factors. The overall rate of prematurity was 18%. Preterm labor was more frequent with ultrasonographic evaluation (52%) than with pelvic examination (25%) (p less than 0.05). The group evaluated by ultrasonography received oral tocolytic agents (55%) more than the group that had pelvic examinations (21%) (p less than 0.02). The groups did not differ in infant birth weights, length of gestation, or neonatal mortality or morbidity. In this prospective randomized study of patients at risk for preterm birth, patients under surveillance by ultrasonographic assessment of the cervix did not fare better than those assigned to bimanual examination. PMID- 2193519 TI - Treatment of twins with hydramnios. PMID- 2193520 TI - Hydramnios in twin pregnancy. PMID- 2193521 TI - Study of preterm birth draws different interpretation. PMID- 2193522 TI - Vaginal ultrasonography in the diagnosis of ectopic pregnancy. PMID- 2193523 TI - Archaeoparasitology in North America. AB - The study of prehistoric parasitism through analysis of coprolites, mummies, skeletons, and latrine soils is rapidly growing. Its development in North America is interdisciplinary and is derived from the fields of physical anthropology, parasitology, and archaeology. The various parasite finds from North America are reviewed. The data show that prehistoric peoples in North America suffered from a variety of parasitic diseases. The validity of the findings are then considered. Although most finds of parasites from prehistoric contexts result from human infections, some finds cannot be verified as such. However, in combination with data from South America, it is clear that prehistoric peoples in the Americas were host to a variety of human parasites, some of which were not previously thought to be present before historic times. PMID- 2193524 TI - Nickel inhibits endothelin-induced contractions of vascular smooth muscle. AB - Endothelin (ET)-induced contractions of vascular smooth muscle (VSM) are dependent on extracellular Ca2+ yet display only partial sensitivity to L-type Ca2+ antagonists. The purpose of this study was to evaluate the effect of nickel (Ni2+), a Ca2+ channel antagonist with clearly documented differential potency toward L- vs. T-type Ca2+ currents on ET-mediated contractions in VSM. Treatment of rings of left anterior descending porcine coronary artery (LAD) with Ni2+ produced a profound dose-dependent inhibition of isometric force development in response to porcine ET (ET-1). At a concentration of 360 microM, Ni2+ exerted a significant inhibitory effect on contracture in response to doses of ET-1 ranging from 3 to 100 nM. In contrast, the same concentration of Ni2+ failed to significantly affect peak force development in response to KCl depolarization (5 77 mM) or to phenylephrine (0.3-30 mM). In addition, 360 microM Ni2+ significantly inhibited the contractile response of rat aorta to 10 nM ET-1. We conclude that ET-1 activates a Ni2(+)-sensitive process in VSM which may signal an additional Ca2+ influx pathway that appears to be functionally distinct from the L-type Ca2+ channel. PMID- 2193525 TI - Effects of changes of pH on the contractile function of cardiac muscle. AB - It has been known for over 100 years that acidosis decreases the contractility of cardiac muscle. However, the mechanisms underlying this decrease are complicated because acidosis affects every step in the excitation-contraction coupling pathway, including both the delivery of Ca2+ to the myofilaments and the response of the myofilaments to Ca2+. Acidosis has diverse effects on Ca2+ delivery. Actions that may diminish Ca2+ delivery include 1) inhibition of the Ca2+ current, 2) reduction of Ca2+ release from the sarcoplasmic reticulum, and 3) shortening of the action potential, when such shortening occurs. Conversely, Ca2+ delivery may be increased by the prolongation of the action potential that is sometimes observed and by the rise of diastolic Ca2+ that occurs during acidosis. This rise, which will increase the uptake and subsequent release of Ca2+ by the sarcoplasmic reticulum, may be due to 1) stimulation of Na+ entry via Na(+)-Ca2+ exchange; 2) direct inhibition of Na(+)-Ca2+ exchange; 3) mitochondrial release of Ca2+; and 4) displacement of Ca2+ from cytoplasmic buffer sites by H+. Acidosis inhibits myofibrillar responsiveness to Ca2+ by decreasing the sensitivity of the contractile proteins to Ca2+, probably by decreasing the binding of Ca2+ to troponin C, and by decreasing maximum force, possibly by a direct action on the cross bridges. Thus the final amount of force developed by heart muscle during acidosis is the complex sum of these changes. PMID- 2193526 TI - Estimation of glucose kinetics in fetal-maternal studies: potential errors, solutions, and limitations. AB - We investigated whether errors occur in the estimation of ovine maternal-fetal glucose (Glc) kinetics using the isotope dilution technique when the Glc pool is rapidly expanded by exogenous (protocol A) or endogenous (protocol C) Glc entry and sought possible solutions (protocol B). In protocol A (n = 8), after attaining steady-state Glc specific activity (SA) by [U-14C]glucose (period 1), infusion of Glc (period 2) predictably decreased Glc SA, whereas. [U-14C]glucose concentration unexpectedly rose from 7,208 +/- 367 (means +/- SE) in period 1 to 8,558 +/- 308 disintegrations/min (dpm) per ml in period 2 (P less than 0.01). Fetal endogenous Glc production (EGP) was negligible during period 1 (0.44 +/- 1.0), but yielded a physiologically impossible "negative" value of -2.1 +/- 0.72 mg.kg-1.min-1 during period 2. When the fall in Glc SA during Glc infusion was prevented by addition of [U-14C]glucose admixed with the exogenous Glc (protocol B; n = 7), EGP was no longer "negative." In protocol C (n = 6), sequential infusions of four increasing doses of epinephrine serially decreased SA, whereas tracer Glc increased from 7,483 +/- 608 to 11,525 +/- 992 dpm/ml plasma (P less than 0.05), imposing an obligatory underestimation of EGP. Thus a tracer "mixing" problem leads to erroneous estimations of fetal Glc utilization and Glc production via the three-compartment model in sheep when the Glc pool is expanded exogenously or endogenously. These errors can be minimized by maintaining the Glc SA relatively constant. PMID- 2193527 TI - Peripheral effects of insulin dominate suppression of fasting hepatic glucose production. AB - Insulin may suppress hepatic glucose production directly, or indirectly via suppression of release of gluconeogenic substrates from extrasplanchnic tissues. To compare these mechanisms, we performed insulin dose-response experiments in conscious dogs at euglycemia, during somatostatin infusion, and intraportal glucagon replacement. Insulin was sequentially infused either intraportally (0.05, 0.20, 0.40, 1.0, 1.4, and/or 3.0; protocol I) or systemically at half the intraportal rate (0.025, 0.10, 0.20, 0.50, 0.70, and/or 1.5 mU.min-1.kg-1; protocol II). Exogenous glucose infused during clamps was labeled with 3 [3H]glucose (2 microCi/g) to prevent a fall in plasma specific activity (P greater than 0.2) that may have contributed to previous underestimations of hepatic glucose output (HGO). Portal insulins were up to threefold higher during intraportal infusion, but peripheral insulin levels were not different between the intraportal and systemic protocols [7 +/- 5 vs. 9 +/- 1, 12 +/- 4 vs. 13 +/- 6, 16 +/- 3 vs. 27 +/- 5, 70 +/- 23 vs. 48 +/- 8, 83 +/- 3 vs. 86 +/- 21, and 128 vs. 120 +/- 14 microU/ml for paired insulin doses; P greater than 0.06 by analysis of variance (ANOVA)]. Despite higher portal insulin levels in protocol I, HGO suppression was equivalent in the two protocols when systemic insulin was matched, from 3.3 +/- 0.1 to near-total suppression at 0.3 mg.min-1.kg-1 at the highest insulin infusion rate (3.0 mU.min-1.kg-1; P less than 0.0001) with intraportal insulin, from 2.9 +/- 0.8 to -0.8 +/- 0.2 mg.min-1.kg-1 in protocol II (P less than 0.001). Suppression of HGO was similar at matched systemic insulin, regardless of portal insulin, suggesting the primacy of insulin's action on the periphery in its restraint of hepatic glucose production. PMID- 2193528 TI - Insulin secretion in Walker 256 tumor cachexia. AB - The effect of cachexia on insulin secretion was examined in adult male rats. Isolated islets of Langerhans from Walker 256 tumor-bearing rats secreted less insulin by glucose stimuli as compared with the control group; this was accompanied by significant change in 45Ca2+ outflow rate. Reduced insulin secretion to glucose stimuli in tumor-bearing rats probably led to low insulinemia (one-third). These findings indicate that reduced insulin secretion is probably an important factor for the development of cachexia in Walker 256 tumor-bearing rats. PMID- 2193529 TI - Constant specific activity input allows reconstruction of endogenous glucose concentration in non-steady state. AB - In vivo studies on the glucose system often require its perturbation by an exogenous input of glucose, whereas glucose turnover is assessed by infusing a glucose tracer. The constant infusion represents the usual format of tracer administration, but it has no clear advantage other than simplicity. Here we propose a different tracer infusion format. It consists of infusing the tracer in parallel with unlabeled glucose so as to maintain a constant specific activity in the infusate. This protocol does not increase experimental complexity and provides new information on the glucose system in non-steady state by allowing reconstruction of the endogenous component of glucose concentration. This reconstruction only requires very general assumptions, such as tracer-tracee indistinguishability and mass conservation; in particular it is independent of the glucose model structure, i.e., number of compartments and their interconnections. A proof of the result is given for a general nonlinear model of the glucose system. The constant specific activity input is also advantageous for non-steady-state calculations, because it reduces the variation in the measured plasma glucose specific activity. The glucose system has served as the prototype, but the protocol is applicable to other blood-borne substances. The radioactive tracer case has been considered, but the same results apply to stable isotope tracers as well; in this case they also become relevant in a somewhat different context, i.e., kinetic studies in steady state. PMID- 2193530 TI - Hepatic apo B-100 lipoproteins and plasma LDL heterogeneity in African green monkeys. AB - The contribution of hepatic apolipoprotein (apo) B-100 lipoproteins to plasma low density lipoprotein (LDL) metabolic heterogeneity was examined in African green monkeys. Hepatic 3H-labeled very low-density lipoproteins (VLDL) (d less than 1.006, where d is density in g/ml) or hepatic 131I-labeled LDL (1.030 less than d less than 1.063) were isolated from perfused livers and injected simultaneously with autologous plasma 125I-LDL into African green monkeys. Serial blood samples were taken, and the distribution of radioactivity among various subfractions of apo B-100 lipoproteins was determined using density-gradient ultracentrifugation. Compartmental models were developed to describe simultaneously the kinetics of hepatic lipoproteins and plasma LDL. In five of seven studies, the metabolic behavior of LDL derived from radiolabeled hepatic lipoprotein precursors differed from the metabolic behavior of radiolabeled autologous plasma LDL. These differences could be described by different models supporting two hypotheses with different physiological interpretations: 1) lipoproteins of donor and recipient animals are kinetically distinct, and/or 2) plasma LDL derived from various potential sources are kinetically distinct. Compartmental modeling was used to test these hypotheses, which were not accessible to testing by conventional experimental methodologies. The kinetic analyses of these studies suggest that plasma LDL may be derived from a variety of precursors, including hepatic VLDL and hepatic LDL, with each source giving rise to metabolically distinct plasma LDL. PMID- 2193531 TI - Enhancement of hepatic glycogen by gluconeogenic precursors: substrate flux or metabolic control? AB - After a meal or glucose load, most carbons of hepatic glycogen are derived from gluconeogenesis. In vitro, hepatic glycogen accumulation is sluggish with glucose alone but markedly enhanced in the presence of gluconeogenic substrates. These findings conflict with the classical view that glucose is the major precursor of hepatic glycogen and have been termed the "glucose paradox." In this review, we attempt to elucidate the central mechanism underlying the glucose paradox by critically examining the in vitro data of hepatic glycogen accumulation. Our analysis is inconsistent with the current hypothesis that glucose phosphorylation is rate limiting for hepatic glycogen accumulation from glucose and that gluconeogenesis enhances glycogen accumulation primarily by increasing substrate flux to the hepatic glucose 6-phosphate pool. Instead, our analysis leads us to the conclusion that the rate-limiting step is the net incorporation of glucose 6 phosphate into glycogen, which is synergistically facilitated with glucose and gluconeogenic substrates. Thus gluconeogenic substrates are involved in the regulation of key enzyme(s) of glycogen metabolism. In addition, in the livers from fasted rats there is substantial cycling through glycogen, and that suppression of glycogen degradation may be a major mechanism in the enhancement of glycogen accumulation by gluconeogenic substrates. Thus we propose a specific hypothesis of the role of gluconeogenic substrates in glycogen metabolism (i.e., inhibition of phosphorylase), which can be tested by future studies. PMID- 2193532 TI - Role of insulin and branched-chain amino acids in regulating protein metabolism during fasting. AB - This study examines the independent effects of insulin and amino acids on protein metabolism after a 12-h and 4-day fast in healthy volunteers. Leucine (Leu) kinetics were examined during sequential insulin infusions of 0 (group I) or 0.0125 (groups II and III), 1.2, and 10 mU.kg-1.min-1. Plasma Leu was maintained at 12-h fasted levels in groups I and II and at 84-h fasted levels in group III. Four-day fast (vs. 1 day, P less than 0.01) was associated with a 79% drop in plasma insulin and elevations in plasma Leu (122%), Leu rates of appearance (Ra) (21%), and Leu oxidation (56%), and no change in nonoxidative rates of disappearance (Rd). Insulin resulted in a dose-dependent suppression of endogenous Leu Ra with group III = I greater than II. Leu oxidation rose 1.7-fold in group III at the highest insulin dose but remained stable in the two other groups. In conclusion, 4-day fasting is associated with enhanced proteolysis and Leu oxidation with no change in nonoxidative Rd (protein synthesis). Elevated branched-chain (and other) amino acids were required to restore tissue sensitivity and specificity to the effects of insulin on protein metabolism after 4 days of fasting. PMID- 2193533 TI - Interstitial glycerol concentration measured by microdialysis in two subcutaneous regions in humans. AB - Interstitial glycerol concentrations were measured in the abdominal and femoral subcutaneous tissue in 10 lean and 6 obese subjects. In the lean subjects [waist hip circumference ratio (WHR) 0.89 +/- 0.01] the fasting interstitial glycerol concentrations in the abdominal and femoral regions were 185 +/- 20 and 160 +/- 15 (SE) microM, respectively, whereas glycerol in venous plasma was considerably lower (66 +/- 5 microM). After an oral glucose load (100 g) the interstitial glycerol concentrations declined but remained higher than in plasma. In obese subjects (WHR 1.1 +/- 0.03) the fasting interstitial glycerol levels were higher, in both regions, than in lean individuals. Furthermore, interstitial glycerol in the abdominal site (291 +/- 32 microM) was significantly higher than in the femoral fat (210 +/- 13 microM; P less than 0.05), while plasma glycerol was similar to that in lean subjects (80 +/- 12 microM). Interstitial glycerol remained higher in the obese than in the lean subjects also after an oral glucose load, but the regional differences were less apparent. Thus interstitial glycerol is higher in the subcutaneous tissue than in venous blood. The data also suggest that lipolysis is enhanced in the abdominal subcutaneous tissue as compared with the femoral site in obese subjects and that lipolysis is exaggerated in both regions in obese as compared with lean individuals. PMID- 2193534 TI - Effect of exercise on insulin action, glucose tolerance, and insulin secretion in aging. AB - To assess the effect of exercise training on the insulin resistance and impaired pancreatic B-cell function of aging, we studied 13 healthy older men (ages 61-82 yr) before and after 6 mo intensive endurance exercise. An index of insulin sensitivity (SI) was measured using Bergman's minimal model. Intravenous glucose tolerance was quantified using the glucose disappearance constant (KGlc) while oral glucose tolerance was assessed after a 100-g glucose load. B-cell function was evaluated by measuring the acute insulin response (AIR) to glucose injection at fasting glucose (AIRGlc) and the AIR to arginine at multiple clamped glucose levels. Exercise produced an endurance training effect as demonstrated by an 18% increase in maximum O2 consumption (VO2max) [38.2 +/- 1.4 to 45.0 +/- 1.1 (SE) ml.kg fat-free mass-1.min-1, P less than 0.001]. An unchanged fasting glucose (5.3 +/- 0.2 to 5.4 +/- 0.2 mM) despite a reduced fasting insulin (61 +/- 6 to 48 +/- 6 pM, P less than 0.01) suggested exercise training improved insulin sensitivity. This was confirmed by a 36% increase in SI from 3.47 +/- 0.41 to 4.71 +/- 0.42 x 10(-5) min-1/pM (P = 0.01). Intravenous glucose tolerance did not change as measured by KGlc, which was 1.46 +/- 0.09 before and 1.48 +/- 0.16%/min after exercise training. Likewise, the incremental glucose response to oral glucose (633 +/- 49-618 +/- 45 mM.min) was unchanged. B-cell function was decreased as reflected by AIRGlc (351 +/- 73-245 +/- 53 pM, P less than 0.01) and the AIRArg at maximal glycemic potentiation (AIRmax, 1,718 +/- 260-1,228 +/- 191 pM, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2193535 TI - Effect of epinephrine on amino acid and energy metabolism in humans. AB - Epinephrine was infused for 8.5 h into five normal, healthy, young adult men on four different occasions at 0, 0.5, 1, and 2 micrograms/min to elevate circulating levels of epinephrine into the high physiological range as seen in stress and trauma. Energy expenditure, heart rate, and blood pressure were measured at hourly intervals. [1-13C]leucine, [ring-2H5]phenylalanine, and [2 15N]glutamine were infused during the last 3.5 h to follow essential amino acid and glutamine kinetics. This design was adapted to study the effects of epinephrine on energy and protein metabolism after acute and temporary metabolic responses to epinephrine had occurred. Plasma glucose was significantly increased by approximately 20 mg/dl from 83 mg/dl (saline infusion) at all levels of epinephrine infusion. Amino acid levels were depressed with epinephrine infusion, with the largest drop occurring for the essential amino acids (-27% at the 2.0 micrograms/min dose). Energy expenditure was increased with epinephrine infusion in a dose-dependent fashion (+17% increase at 2.0 micrograms/min infusion). These effects were sustained for the duration of 8.5 h epinephrine infusion. There was no significant change in leucine or phenylalanine flux, indicative of protein breakdown, or in leucine oxidation. Glutamine flux was significantly (but modestly, +7%) increased at only the 2.0-micrograms/min infusion rate. Changes in kinetics that altered amino acid levels were not apparent by 7 h of epinephrine infusion (the beginning of the plateau period for the tracer infusion study). Although epinephrine can produce long-term elevations of metabolic rate, its effects on protein metabolism are minimal beyond acute changes affecting amino acid levels. PMID- 2193536 TI - Direct effect of parathyroid hormone on insulin secretion from pancreatic islets. AB - Indirect evidence indicates that parathyroid hormone (PTH) interacts with pancreatic islets and modulates their insulin secretion. This property of PTH has been implicated in the genesis of impaired insulin release in chronic renal failure. We examined the direct effect of PTH-(1-84) and PTH-(1-34) on insulin release using in vitro static incubation and dynamic perifusion of pancreatic islets from normal rats. Both moieties of the hormone stimulated in a dose dependent manner glucose-induced insulin release but higher doses inhibited glucose-induced insulin release. This action of PTH was modulated by the calcium concentration in the media. The stimulatory effect of PTH was abolished by its inactivation and blocked by its antagonist [Tyr-34]bPTH-(7-34)NH2. PTH also augmented phorbol ester (TPA)-induced insulin release, stimulated adenosine 3',5' cyclic monophosphate (cAMP) generation by pancreatic islets, and significantly increased (+50 +/- 2.7%, P less than 0.01) their cytosolic calcium. Verapamil inhibited the stimulatory effect of PTH on insulin release. The data show that 1) pancreatic islets are a PTH target and may have PTH receptors, 2) stimulation of glucose-induced insulin release by PTH is mediated by a rise in cytosolic calcium, 3) stimulation of cAMP production by PTH and a potential indirect activation of protein kinase C by PTH may also contribute to the stimulatory effect on glucose-induced insulin release, and 4) this action of PTH requires calcium in incubation or perifusion media. PMID- 2193537 TI - Regulation of pancreatic duct epithelial growth in vitro. AB - Effects of a number of possible trophic factors on growth of guinea pig pancreatic duct epithelial monolayers were investigated. Isolated fragments of main and interlobular ducts were prepared and explanted onto both tissue culture plastic and thick gels of type I collagen. Monolayers growing out from explants were first cultured in a basal medium for 3 or 4 days. Next, the medium was supplemented individually with bombesin, carbachol, caerulein, epidermal growth factor (EGF), secretin, 12-O-tetradecanoylphorbol 13-acetate (TPA), or vasoactive intestinal peptide (VIP). Cells were cultured in the absence or presence of these possible trophic factors, and monolayer areas were determined morphometrically at 0, 2, and 4 days. Rate of growth was determined from increase in area over each 2 day period. Monolayers grown in basal medium alone on plastic increased to 479% of initial area over the 4-day test period; those grown on collagen increased to 523%. Explants cultured in presence of bombesin, carbachol, caerulein, secretin, TPA, and VIP on either substrate grew at rates not significantly different from those cultured in basal medium. By contrast, duct monolayers grown on plastic or collagen in presence of 10 nM EGF expanded in area to 722 and 1,070%, respectively, of their initial areas. The EC50 for this trophic effect was approximately 1 nM. These results show that EGF exerts a potent trophic effect on guinea pig pancreatic duct cells in vitro but also indicate that cell division in the pancreatic main and interlobular ducts is not regulated by caerulein and related peptide hormones that have been reported to have growth-promoting effects on exocrine pancreas in vivo. PMID- 2193538 TI - Decrease in rat submandibular acinar cell volume during ACh stimulation. AB - Changes in acinar cell volume were measured in the perfused submandibular gland of the rat at 23 degrees C during salivary secretion induced by acetylcholine (ACh). Cellular volume was monitored by two methods: the impedance method and the morphometric method using video-enhanced contrast optical microscopy. Both measurements revealed a decrease in acinar cell volume in response to 1 microM ACh. Within the 1st min of stimulation, secretion increased to the initial maximum (initial secretion), and cell shrinkage occurred. During sustained stimulation, secretory rate and cell volume were maintained at the plateau level (steady secretion). The decrease in cell volume was 71.8 +/- 2.9% of resting volume (means +/- SE, n = 8) as measured by the impedance method and 76.1 +/- 2.0% (n = 20) as measured by the morphometric method. With the removal of ACh, cell volume increased to 111.6 +/- 2.7% (n = 8) of the prestimulation level as measured by the impedance method and 108.8 +/- 1.5% (n = 20) as measured by the morphometric method, and then recovered to the prestimulation level slowly. The weight of the gland decreased significantly during stimulation. These findings proved that volume decrease occurred during stimulation. The measurement of cell volume gave the net fluid flux of the acinar cell compartment. The net fluid flux and the rate of salivary secretion gave an estimation of the fluid influx across the basolateral membrane. These findings suggest that a transcellular route for fluid secretion exists in the salivary gland. PMID- 2193539 TI - Epithelial modulation of airway smooth muscle. AB - The responsiveness of airway smooth muscle is influenced by the functional integrity of the respiratory epithelium. The nature of this regulatory action by the epithelium remains largely unresolved. Several explanations may account for the epithelium-dependent responses induced by numerous stimuli. This review will present and discuss the evidence suggesting that the epithelium generates an inhibitory signal or signals that function to modulate the responsiveness of the underlying smooth muscle. In addition, the possible candidates for the identity of this epithelium-derived relaxing factor or factors will be assessed. Finally, the mechanisms by which the epithelium-derived relaxing factors may act to modulate bronchomotor tone will be discussed. PMID- 2193540 TI - Cellular basis of transduction in carotid chemoreceptors. AB - Understanding transduction mechanisms is central to much of sensory physiology. The carotid chemoreceptors monitor the PO2 of arterial blood en route to the brain and are powerfully excited when the arterial PO2 falls to less than 60 mmHg. The type I cell is generally believed to be the transducer. These cells release catecholamines in response to agents that excite the receptor (hypoxia, cyanide, K(+)-induced depolarization, etc.). Adherent to the cells are the saucer shaped nerve endings of the axons of the sinus nerve. We and others have used patch-clamp techniques to study the electrophysiological properties of the type I cells. We have also investigated type I cell chemistry with microfluorometric techniques, to measure intracellular Ca2+ concentration ([Ca2+]i), mitochondrial NADH, and mitochondrial membrane potential (delta psi m). During hypoxia there are graded increases in NADH, [Ca2+]i (which presumably will promote transmitter release), and graded depolarization of delta psi m. These results suggest that the Ca2+ is largely derived from an intracellular store, probably from mitochondria, and that release is entrained to delta psi m. Comparative studies with other cells indicate an increased sensitivity of the mitochondria of type I cells to changes in PO2. The data suggest that the electrophysiological responses of type I cells to hypoxia are not central to the response, although the excitability of the cells may provide a mechanism for the modulation of the response by varying voltage-gated Ca2+ influx. PMID- 2193541 TI - Acetazolamide and insulin alter choroid plexus epithelial cell [Na+], pH, and volume. AB - Agents that inhibit or stimulate Na+ transport were tested for their effects on the ionic composition and volume of the in vivo choroid plexus (CP) epithelium. Ketamine-anesthetized adult Sprague-Dawley rats treated 1 h with acetazolamide or insulin were analyzed for choroid cell [Na+]i, [HCO3-]i, and pHi (dimethadione method); for transmembrane Na+ and H+ gradients; and for the kinetics of penetration of 22Na from plasma to plexus epithelium to CSF. Acetazolamide (25 mg/kg) reduced [Na+]i by 5-10 mmol/l and substantially elevated [HCO3-]i and pHi; the concurrent 22Na uptake by the in vivo choroid plexus and CSF, as quantified by the transfer coefficient, Kin (ml.g-1.h-1), was curtailed by 55-60%. Such effects on Na+ transport and distribution are likely secondary to the alkalinization of pHi induced by carbonic anhydrase inhibition. Conversely, insulin (3 U/kg ip) stimulated Na+ transport, i.e., manifested as enhanced uptake of 22Na from plasma to choroid cell and increased [Na+]i. For various treatments altering the basolateral membrane H+ gradient, the regression analysis of the 22Na Kin vs. log [H+]i/[H+]ISF (where ISF is interstitial fluid) was significant at P less than 0.01. This is consistent with effects mediated by Na(+)-H+ exchange. K+ and Cl- redistribution phenomena were coincident with altered Na+ transport, as choroidal cells retained K+, Cl-, and H2O after acetazolamide but lost K+, Cl-, and H2O with insulin treatment. A model is presented relating alterations in CP Na+ transport, KCl content, and cell volume. Overall, the findings encourage the postulate for effects of these drugs on Na+ transport basolaterally, either indirectly by attenuating [H+]i/[H+]ISF (acetazolamide) or directly by accelerating Na+ transport (insulin). PMID- 2193542 TI - Insulin stimulates phosphate transport in opossum kidney epithelial cells. AB - Insulin is antiphosphaturic in vivo and this effect is due, in part, to increased Na(+)-dependent phosphate uptake across the luminal brush-border membrane of the proximal tubule. The intracellular mechanism is not understood. The present study shows that the stimulatory effect of insulin on phosphate transport can be reproduced in opossum kidney (OK) cells, suggesting that this established renal epithelial cell line may be a good model for further studies on insulin action on renal phosphate transport. The stimulation by insulin was dose related when insulin was used at concentrations within the range of 10(-14) to 10(-8) M. At 10(-8) M, insulin had no effect on Na(+)-independent uptake of phosphate or on the Na(+)-dependent uptakes of methyl-alpha-D-glucopyranoside and glutamate. The onset of insulin action on phosphate uptake was detected within 15 min, and the stimulation was reversed completely within 30 min after removal of insulin from the medium. Insulin action was not blocked by protein synthesis inhibitors and was not altered by bacitracin, an inhibitor of intracellular degradation of insulin. Pretreatment with the calcium-channel blockers, nifedipine and verapamil (10(-4) M), produced significant increases in the stimulatory effect of insulin, suggesting indirectly that insulin action on phosphate uptake may be influenced by Ca2+. In contrast to in vivo studies, there was no evidence that insulin interfered with parathyroid hormone action on OK cells. PMID- 2193543 TI - Superiority of salt restriction over diuretics in reducing renal hypertrophy and injury in uninephrectomized SHR. AB - Spontaneously hypertensive rats (SHR) were uninephrectomized (UNX) at 6 wk of age and given either standard chow (CON), low-sodium chow (LSC), or standard chow and hydrochlorothiazide (HCTZ) added to the drinking water. Severe hypertension developed in all three groups. Forty-two weeks after UNX, proteinuria and glomerular sclerosis were significantly lower in LSC than in CON or HCTZ. The protective effect of salt restriction did not depend upon alterations in plasma renin concentration or glomerular hemodynamics. Micropuncture revealed that glomerular pressure was high in all three groups. Renal hypertrophy assessed by kidney weight, kidney-to-body weight ratio, glomerular volume, and glomerular capillary radius were reduced by salt restriction. These findings suggest that, in the setting of glomerular hypertension, hypertrophy promotes sclerosis. Salt restriction inhibits compensatory kidney growth and protects the kidney. PMID- 2193544 TI - Hemodynamic and hormonal effects of renin inhibition in ovine heart failure. AB - The effects of renin inhibition have not previously been documented in established heart failure (HF). Accordingly, we investigated the acute hemodynamic and hormonal effects of a renin inhibitor (EMD 52297) in an ovine model of HF induced by rapid ventricular pacing (LVP). In seven sheep, recordings were made for 1 h before, during a 2-h infusion of renin inhibitor (RI) or vehicle, and after each infusion on the 5th and 6th day after commencing LVP. The RI (20 micrograms.kg-1.min-1) or vehicle was given in random order. RI infusion induced a rapid fall in plasma renin activity (PRA) and angiotensin II, reaching a nadir at 20 min. The vasodilator response was characterized by a 16% fall in mean arterial pressure (MAP), which was related to the fall in PRA (r = 0.78, P less than 0.05). MAP and PRA remained suppressed throughout the infusion period, and both returned to preinfusion levels within 10 min of terminating infusions. Left atrial pressure and plasma aldosterone were not significantly altered, while renal function was preserved despite the fall in perfusion pressure. RI has significant hemodynamic actions in a model of established HF. PMID- 2193545 TI - Coronary oscillatory flow amplitude is more affected by perfusion pressure than ventricular pressure. AB - In this study on the isolated, maximally vasodilated, blood-perfused cat heart we investigated the relation between left ventricular developed pressure (delta Piv) and coronary oscillatory flow amplitude (diastolic minus systolic flow, delta F) at different levels of constant perfusion pressure (Pp). We hypothesized that the effect of cardiac contraction on the phasic flow results from the changing elastic properties of cardiac muscle. The coronary vessel compartment can, as can the left ventricular lumen compartment, be described by a time-varying elastance. This concept predicts that the effect of left ventricular pressure on delta F is small, whereas the effect of Pp is considerable. Both the waterfall model and the intramyocardial pump model predict the inverse. The relation between delta Piv and delta F at a Pp of 10 kPa is delta F = (4.71 +/- 3.08).delta Piv + 337 +/- 75 (slope in ml.min-1.100 g-1.kPa-1 and intercept in ml.min-1.100 g-1; n = 7); the relation between (constant levels of) Pp and delta F at a constant delta Piv of 10 kPa is delta F = 51.Pp + 211 (slope in ml.min-1.100 g-1.kPa-1 and intercept in ml.min-1.100 g-1; n = 6). The differences in slope are best predicted by the time varying elastance concept. PMID- 2193546 TI - Resource sharing in rat gestation: role of maternal cardiovascular hemodynamics. AB - There is a substantial decrease in blood pressure (BP) in late pregnancy in the laboratory rat. It is so pronounced that manipulations that produce sustained elevations in BP in nonpregnant animals have little or no effect during pregnancy. It is commonly believed that this decrease in BP is a consequence of a large decrease in total peripheral resistance resulting from the passive combination of the placental vasculature with a preexisting maternal vasodilation. An alternative view is presented here. We suggest that, in small mammals like the laboratory rat, pregnancy severely challenges the ability of the maternal cardiovascular system to meet its metabolic demands, so that during the last stages of maturation of the low-resistance placental circulation delivery of vital metabolic or nutritional substances to the maternal vasculature becomes marginal. When the so-called maternal hemodynamic preservation threshold is reached, a pronounced and wide-spread vasodilation occurs to maintain adequate perfusion of maternal organs. The late-gestational decrease in BP thus reflects a dynamic interaction between the maternal and placental circulations rather than reflecting their passive combination. The hypothesis provides a framework for the integrated discussion of a number of important phenomena: the fact that hypertensive rats exhibit a larger decrease in BP in late gestation than normotensive rats; the existence of a positive association between litter size and the magnitude of the late-gestational decrease in BP; and, finally, the well established ability of the food-restricted pregnant rat to compartmentalize its nutritional resources. PMID- 2193547 TI - Fetal swallowing: correlation of electromyography and esophageal fluid flow. AB - Patterns of fetal drinking behavior were quantified in five singleton fetuses (128 +/- 1 days gestation) by computer analysis of laryngeal-esophageal electromyography (EMG) and thoracic esophageal fluid flow. Esophageal flow was noted to be bidirectional with an average antegrade flow-to-retrograde flow ratio of 4.4 +/- 1.5. Retrograde esophageal flow coincided with diaphragmatic contractions, suggesting that inspiratory gastroesophageal pressure gradients may be operative. The regurgitated fluid was returned to the fetal rumen by thoracic esophageal contractions. Significant net fluid intake was noted during periods of primarily unidirectional antegrade esophageal flow. Fetuses swallowed an average of 35 +/- 9 ml/h during the 12-h study, extrapolating to an average daily volume of 840 +/- 224 ml. An EMG "propagated swallow" representing coordinated contractions of the thyrohyoid, nuchal esophagus, and thoracic esophagus averaged 43 +/- 3 swallows/h and was highly correlated with net esophageal flow. Nearly 60% of the total fluid intake occurred during "bouts" of propagated swallows, which represented only 8% of the study period. Bouts averaged 11.7 +/- 0.4 propagated swallows, lasted 2.1 +/- 0.2 min, and occurred every 27.6 +/- 1.7 min. Although EMG swallowing activity was similar, there were significant differences among fetuses in net esophageal fluid flow and volume per propagated swallow. We speculate that fetal fluid intake is dependent on the availability and physical properties of the swallowed fluid, whereas swallowing activity is primarily related to cortical maturation and thirst stimulation. PMID- 2193548 TI - Baroreflex control of sympathetic outflow in pregnant rats: effects of captopril. AB - Arterial baroreflex control of renal sympathetic nerve activity (RSNA) was compared in nonpregnant (NP) and near-term pregnant (P) chloralose-anesthetized rats. Baroreflex curves were obtained by recording reflex changes in RSNA (expressed as a percent of base line) due to increases and decreases in mean arterial pressure (MAP) [intravenous phenylephrine and nitroprusside (NTP)]. The slope, midpoint (EP50), and threshold pressures of the baroreflex curves were compared. Base-line MAP was significantly lower in the pregnant animals (P = 96 +/- 3 vs. NP = 113 +/- 5 mmHg). The baroreflex curves of pregnant animals also had significantly lower threshold (P = 95 +/- 3 vs. NP = 110 +/- 5 mmHg) and midpoint values (P = 105 +/- 4 vs. NP = 119 +/- 5 mmHg). The response to unloading the baroreceptors was attenuated in the pregnant animals as indicated by a decrease in slope of the NTP portion of the baroreflex curve (P = 0.95 +/- 0.17 vs. NP = 1.61 +/- 0.29% nerve activity/mmHg). Responses to blockade of angiotensin-converting enzyme with captopril (2 mg/kg iv) were also examined. There were no differences in EP50 or slope among the control, captopril, and recovery baroreflex curves within either the nonpregnant or pregnant animals. However, after captopril, MAP decreased to a greater extent in the pregnant rats, yet RSNA increased to the same level for the two groups. Thus pregnancy results in a leftward shift of the baroreflex function curve toward a lower operating pressure range. In addition, pregnant rats demonstrated an impaired ability to increase sympathetic outflow above base-line values in response to a hypotensive challenge. PMID- 2193549 TI - Area postrema: essential for support of arterial pressure after hemorrhage in rats. AB - Previous studies have indicated that the area postrema (AP) of the rat is necessary for the development of chronic angiotensin-dependent hypertension. The present study assesses the role of the AP in the maintenance of arterial pressure during hemorrhage. Sprague-Dawley rats were given sham or AP lesions 1 wk before the experiment. They were instrumented with femoral arterial and venous catheters 2 days before the experiment. On the day of the experiment, base-line mean arterial pressure (MAP) was measured for 1 h before hemorrhage. During the following 45 min, each rat was subjected to one 7-ml/kg hemorrhage every 15 min for a total of three hemorrhages. MAP was monitored by computerized data acquisition. As shown previously, MAP was slightly but significantly lower in AP lesion rats compared with sham-lesion rats before the hemorrhage procedure. In AP lesion rats, hemorrhage resulted in a significantly greater fall in arterial pressure than in sham-lesion rats. In spite of larger drops in pressure in AP lesion rats, hemorrhage caused equivalent increases in plasma renin and vasopressin in both groups. In AP-lesion rats compared with sham-lesion rats, significant bradycardia was present before hemorrhage. Hemorrhage caused bradycardia in both sham- and AP-lesion rats relative to the prehemorrhage heart rates, but AP-lesion rats showed greater bradycardia than did sham-lesion rats during every time period. We conclude that the AP may play an important role in the defense of arterial pressure against hemorrhage. PMID- 2193550 TI - Child ataxias: a developmental perspective. AB - In children, the conditions defined as "ataxia" form a very heterogeneous group. They also often differ from the "ataxias" of adults. In many cases this can be attributed to their different etiology, but probably it is also due to the peculiar functional and physiopathologic characteristics of the cerebellar system during the developmental period. In this article we will attempt to critically analyze this subject, with reference to the data published in the literature, to the results of experimental neurophysiologic investigations and, in part, to our own clinical observations. PMID- 2193551 TI - Hypocalcemic hyper-CK-emia in hypoparathyroidism. AB - A 15-year-old boy with increased serum creatine kinase (hyper-CK-emia) due to hypocalcemia in turn caused by idiopathic hypoparathyroidism (HP) is presented. Hyper-CK-emia was incidentally noted while managing a patient, aged nine, with mental retardation, epilepsy and mild hypocalcemia. Neurological examination showed normal deep tendon reflexes and no muscle weakness; electromyogram was normal. The hyper-CK-emia normalized during treatment for the hypocalcemia. Previously reported patients with hypocalcemic hyper-CK-emia or myopathy together with HP are discussed, as well as the degree of hypocalcemia and the wide spectrum of the muscle dysfunction. PMID- 2193552 TI - Computed EEG topography (CET) and childhood epilepsy: two years experience. AB - The statistical data obtained with the use of computed EEG topography (CET) in a diagnostic study on 65 epileptic children are reported briefly. The CET technique has proved to be particularly useful in establishing the focal origin of paroxystic activity in a high percentage of cases of generalized epilepsies presumed to be primary (33%) or secondary (88%), and for localizing areas of brain function abnormality not detected by other diagnostic techniques. PMID- 2193553 TI - [Analysis of data management in anesthesia from an ergonomic viewpoint]. AB - In the perioperative phase the anesthetist has to manage an increasing amount of knowledge, information and data. Using a system-ergonomic approach we can define three types of data management (DM): Exploratory DM, Operative DM, Concluding DM. The preliminary examination of the patient is Exploratory DM. Data are collected and recorded. Here, a well structured form prevents things being forgotten, provides forgetting anything. Help from electronic devices is not available. Control of anaesthesia is based on Operative DM. The anesthetist is part of an ongoing process. He investigates and records a situation based on his knowledge and experience and a prompt reaction to untoward circumstances may be necessary. Today's workplace provides insufficient support for this task. Data presentation is unstructured and distributed around the workplace which produces potentially dangerous overloading in critical situations. It is necessary to view the work layout as an integrated whole. The data being displayed must be hierarchically structured and appropriate to the situation. Concluding DM involves summarising data and information on completion of a process in ways appropriate to specific purposes. With this the anesthetist completes an anaesthesia and transfers the patient to the next unit, e.g. to the recovery room. He has to fill in several forms for clinical and statistical reasons. Electronic aids are available only for parts of some tasks. The goal should be a multifunctional summary satisfactory for clinical and statistical purposes, most aspects of which are created automatically by a computer system. PMID- 2193554 TI - [Inhalation anesthesia with halogenated hydrocarbons: value of isoflurane]. AB - The halogenated hydrocarbons halothane, enflurane and isoflurane are used extensively. Like every other anaesthetic, these inhaled agents are not devoid of side effects, most of which are undesirable. This review summarises the similarities and differences between the actions of these vapours. Although isoflurane appears to be more advantageous than enflurane and halothane in certain patients, isoflurane is no panacea and the question of which agent to choose still has to be answered for every patient. A note of caution is warranted against the further use of halothane in adults, as halothane offers no advantages when compared to enflurane and isoflurane but carries a higher risk of hepatotoxicity. However, in children halothane remains the halogenated agent of first choice, when anaesthesia is induced via face mask. PMID- 2193555 TI - [Postoperative pain therapy with 1-methadone and metamizole. A randomized study within the scope of intravenous on-demand analgesia]. AB - Methadone, a potent long-acting opioid analgesic, is only seldom prescribed for postoperative pain relief in Germany. It was the aim of the present investigation to evaluate its efficacy and to establish an adequate dose range using intravenous patient-controlled analgesia (PCA), as well as to determine possible drug interactions with the antipyretic analgesic metamizol (dipyrone). 120 patients recovering from elective major abdominal, gynaecological or orthopaedic surgery under standardized balanced anaesthesia were randomly allocated to three groups to self-administer intravenous 1-methadone. Demand doses were 0.573 mg (group LD), 1.145 mg (group HD) or 0.573 mg to which 50 mg metamizol (dipyrone) were added (group LM). Infusion rate was set to 0.137 mg 1-methadone/h in every group, lockout time was 1 min. Hourly maximum dose was set to 5.95 mg 1 methadone/h. During an average PCA duration of 21 hours patients demanded mean dosages of 16.4 mg (LD), 18.7 mg (HD) or 13.4 mg (LM) 1-methadone. Although individual variation in drug consumption was high, effective pain relief was possible in all cases. Cardiovascular and respiratory status during the observation period was always normal. 88-93% of patients preferred PCA in comparison with earlier experienced conventional postoperative pain treatment. It is concluded that patients are able to control adequate drug consumption, i.e. to avoid overdosage, by adjusting demand frequency if variable demand dosages are offered. Thus 13-19 mg 1-methadone per day can be recommended as reasonable dose range for pain relief during the early postoperative period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2193556 TI - [Bronchoscopy in ventilated patients: full narcosis or local anesthesia?]. AB - In a prospective, randomised trial bronchoscopy was performed either in local anaesthesia (LA) or general anaesthesia, each on 15 ventilated patients. LA was carried out with oxybuprocain-hydrochloride 1% in repeated doses injected into the trachea and main bronchi, general anaesthesia with midazolam, piritramide and vecuronium bromide. Measurements were performed before, 3 minutes after induction of anaesthesia, immediately after bronchoscopy and 15 and 60 minutes after bronchoscopy. There was no effect on cardiocirculatory function during bronchoscopy in both groups, but we found a decrease in paO2 from 97 to 80 mmHg (median) after application of LA. Subsequent bronchoscopy did not significantly influence paO2. The present study shows that in ventilation patients undergoing fibreoptic bronchoscopy, the application of LA will usually result in a decline of arterial oxygen tension. This procedure should therefore only be performed if general anaesthesia is undesirable, as e.g. in patients being weaned from ventilation. PMID- 2193557 TI - Pulmonary thromboembolism: disease recognition and patient management. PMID- 2193558 TI - Pioneering curare in anesthesia. PMID- 2193559 TI - D-dimer and thrombin-antithrombin III complex levels uncorrelated with phlebographic findings in 11 total knee replacement patients. AB - D-dimer and thrombin-antithrombin III complex (TAT) were assayed in 11 patients at various times pre- and post-operatively in order to determine the possible value of these parameters in screening for thromboembolic complications. Phlebography revealed distal thrombosis in 6 of the 11 patients. The D-dimer level, already elevated before surgery, increased at day 1 and remained high at days 5 and 10. Two methods were used for the assays and showed strongly correlated results. The TAT level increased at day 1 and then progressively returned toward basal values. No difference was observed at any time between patients with or without thrombosis. The results in surgical patients undergoing knee replacement suggest that neither D-dimer nor TAT assays are valid screening procedures for post-operative DVT. Nevertheless, in view of the small number of patient studied, further work is required to confirm these results. PMID- 2193560 TI - Adenosine for paroxysmal supraventricular tachycardia: dose ranging and comparison with verapamil. Assessment in placebo-controlled, multicenter trials. The Adenosine for PSVT Study Group. AB - OBJECTIVE: To assess the safety and efficacy of intravenous adenosine in terminating acute episodes of paroxysmal supraventricular tachycardia. DESIGN: Two prospective, double-blind, randomized, placebo-controlled trials to evaluate dose response in patients receiving adenosine and to compare the effects of adenosine with those of verapamil. PATIENTS: A total of 359 patients with a tachycardia electrocardiographically consistent with paroxysmal supraventricular tachycardia were entered into the two protocols. Patients subsequently found to have arrhythmias other than paroxysmal supraventricular tachycardia were excluded from the efficacy analysis. INTERVENTIONS: The first protocol compared sequential intravenous bolus doses of 3, 6, 9, and 12 mg of adenosine to equal volumes of saline. In the second protocol, patients received either 6 mg and, if necessary, 12 mg of adenosine or 5 mg and, if necessary, 7.5 mg of verapamil. MEASUREMENTS AND MAIN RESULTS: When data are expressed in terms of cumulative response in eligible patients, intravenous adenosine terminated acute episodes of paroxysmal supraventricular tachycardia in 35.2%, 62.3%, 80.2%, and 91.4% of patients who received maximum doses of 3, 6, 9, and 12 mg, respectively, in a four-dose sequence, whereas 8.9%, 10.7%, 14.3%, and 16.1% of patients responded to four sequential placebo doses (P less than 0.0001). In the second trial, cumulative response rates after 6 mg followed, if necessary, by 12 mg of adenosine were 57.4% and 93.4%, and after 5 mg followed, if necessary, by 7.5 mg of verapamil were 81.3% and 91.4%. The average time after injection to termination of tachycardia by adenosine was 30 seconds. Adenosine caused adverse effects in 36% of patients, but they lasted less than 1 minute and were usually mild. CONCLUSIONS: Adenosine in graded doses up to 12 mg rapidly and effectively terminates acute episodes of paroxysmal supraventricular tachycardia in which the atrioventricular node is an integral part of the re-entrant circuit. The overall efficacy of adenosine is similar to that of verapamil, but its onset of action is more rapid. Adverse reactions to adenosine are common but are minor and brief. PMID- 2193562 TI - Minerals and immunity: introduction. PMID- 2193561 TI - Body fluid volume regulation in health and disease: a unifying hypothesis. AB - In studies in experimental animals and in edematous patients, the nonosmotic release of vasopressin has been found to be consistently associated with activation of the sympathetic nervous and renin-angiotensin-aldosterone systems. Moreover, the sympathetic nervous system is known to modulate the nonosmotic release of vasopressin and activation of the renin-angiotensin-aldosterone system. These findings led to our proposal that body fluid volume regulation involves dynamic interaction between cardiac output and peripheral arterial resistance. In this context, neither total extracellular fluid volume nor total blood volume are determinants of renal sodium and water excretion. With a decrease in effective arterial blood volume (EABV) initiated by either decreased cardiac output or peripheral arterial vasodilation, the acute response involves vasoconstriction mediated by angiotensin, sympathetic mediators, and vasopressin. The renal vasoconstriction, which accompanies either decreased cardiac output or peripheral arterial vasodilation, causes a decreased distal tubular delivery of sodium and water, thus maximizing the water-retaining effect of vasopressin and impairing normal escape from the sodium-retaining effect of aldosterone. The elevated glomerular filtration rate and filtered sodium load seen in pregnant women allow increased distal sodium and water delivery despite a decrease in EABV, thus limiting edema formation during gestation. PMID- 2193563 TI - Physiological and pharmacological effects of zinc on immune response. PMID- 2193564 TI - Advances in understanding selenium's role in the immune system. PMID- 2193565 TI - Influence of iron on immunity and disease resistance. PMID- 2193566 TI - The immunotoxic effects of lead in lead-exposed laboratory animals. PMID- 2193567 TI - Antioxidant micronutrients and immune responses. PMID- 2193568 TI - Vitamin A status, resistance to infection, and childhood mortality. PMID- 2193569 TI - Micronutrients and susceptibility to infection. AB - Iron deficiency and vitamin A deficiency are both reported to predispose to infection morbidity and to mortality. In both situations, however, the data are insufficient to draw firm conclusions, primarily owing to flaws in the design of the studies. To be sure, these are difficult studies to carry out, and the investigators whose reports have been reviewed should be praised rather than adversely criticized for their efforts. In the case of iron deficiency, there is a further complication in interpretation, that is the suggestion that iron deficiency states may be protective and that conditions of iron overload may predispose to infection. These concepts appear to pertain most convincingly to malaria and Yersinia infections, and to situations in which iron dextran is given parenterally to young children in the first few months of life. There are still two few data to suggest that oral iron is harmful and there is no reason at present that it should not be employed for the correction of iron deficiency anemia. PMID- 2193570 TI - Micronutrients and immune function in the elderly. PMID- 2193571 TI - Nutrient modulation of autoimmune disease. PMID- 2193572 TI - Infant nutrition and immunity. PMID- 2193573 TI - Human milk: immunologic-nutritional relationships. PMID- 2193574 TI - The role of vitamin E in immune response and disease resistance. AB - Vitamin E supplementation enhances humoral and cell-mediated immunity, and augments the efficiency of phagocytosis in laboratory animals, farm animals, and humans. In its disease protection effect vitamin E interacts with other antioxidant nutrients and with other nutrients in the diet. Other antioxidant nutrients, such as vitamin A and beta carotene, also enhance disease resistance. Beta carotene is effective in combination with vitamin E. The optimal dose of vitamin E for maximum protection depends on many factors; thus it has to be established case by case. The delivery system of vitamin E greatly influences its effectiveness. A targeted delivery to localized immunocompetent cells in adjuvant formulations is far more effective than a general dispersed delivery in a diet. Vitamin E adjuvants provided greater immunoprotection against enterotoxemia and epididymitis in sheep than conventional vaccines. PMID- 2193575 TI - Micronutrient safety. PMID- 2193577 TI - Cytokines and metabolism. PMID- 2193576 TI - Future role of micronutrients on immune functions. AB - The future is bright in the field of micronutrients and immunity. New advances in technology now permit the design of many new research studies, and an increased application of the findings to clinical and public health practices. More investigators will need to be trained in the fundamentals of both nutritional and immunological sciences. More basic information will be needed in both fields, but the scientific and clinical values of merging these two fields are already well established. The development of additional animal models will be needed to dissect out the role of each essential micronutrient and its potential importance in each step of the immune response. Based on future studies, new RDAs must be formulated and applied widely in medical and public health practices and in public education. PMID- 2193578 TI - Metabolic responses to cachectin/TNF. A brief review. AB - Cachectin/tumor necrosis factor (TNF-alpha) is a macrophage-secreted cytokine initially found to be a lipoprotein lipase-suppressing serum factor in cachectic, parasite-infected animals. Cloning of the cDNA encoding the gene for cachectin enabled biosynthesis of recombinant human cachectin and proof that the protein is identical to TNF-alpha. Numerous biological activities have subsequently been attributed to this pluripotent cytokine. In addition to suppressing LPL, cachectin/TNF mediates decreased lipogenic enzyme synthesis in adipocytes, causing a state of "cellular cachexia" in vitro. Similarly, catabolic cellular energy responses are induced by cachectin/TNF in cultured skeletal muscle cells which exhibit accelerated glycogenolysis, enhanced lactate production, and increased expression of hexose transporters. Persistent cachectin/TNF production occurs in chronic infection and malignancy, and chronic exposure induces a cachexia syndrome characterized by anorexia, weight loss, and anemia. Acute systemic appearance of cachectin/TNF is capable of inducing a state of lethal shock, disseminated hemorrhagic necrosis, catabolic hormone release, and multiple organ injury. Inhibiting the toxic effects of cachectin/TNF with monoclonal anti cachectin antibodies during overwhelming Gram-negative bacteremia confers protection against septic shock. In these studies, the unprotected controls succumbed within hours, but baboons immunized against cachectin/TNF did not develop the characteristic increases of IL-1, IL-6, or catabolic stress hormones and did not die, suggesting that cachectin/TNF is a pivotal, proximal factor in the humoral cascade mediating septic shock syndrome. Recent evidence indicates that when produced in lesser quantities, cachectin/TNF may participate in the degradative and reparative mechanisms of physiological tissue remodelling and homeostasis. Future studies of the immunological and metabolic effects of cachectin/TNF should lead to a better understanding of the pathogenesis of infection and inflammation. PMID- 2193579 TI - Interleukin-1, anorexia, and dietary fatty acids. AB - IL-1 and other cytokines mediate several components of both acute and chronic pathological processes observed in patients with cancer and chronic infection. Cachexia ranks as one of the more prominent aspects of several diseases and the present studies demonstrate that recombinant forms of either IL-1 beta or IL-1 alpha reduce food intake in experimental animals. In meal-fed rats, a single injection of IL-1 induces a 40% reduction [table: see text] in food intake, whereas daily injections slow normal weight gain. The anorexic response to IL-1 is prevented by cyclooxygenase inhibitors, although this is unlikely due to a central nervous system effect. Reduced production of cyclooxygenase products such as PGE2 also occurs in rats fed supplemental N-3 fatty acids, and this was associated with a decreased anorexic response to IL-1. Therefore, one mechanism by which IL-1 induces anorexia appears to require cyclooxygenase metabolites, such as PGE2. N-3 fatty acid supplements also reduce the severity of host responses to inflammation and infection. Part of this is due to decreased cyclooxygenase products; however, part also may be due to reduced synthesis of IL 1. Blood leukocytes from human subjects taking oral N-3 supplements produce 60% less IL-1. The ability of N-3 fatty acids to reduce IL-1 synthesis appears to be via the lipoxygenase pathway. Therefore, N-3 fatty acids may be beneficial to patients with anorexia, since such supplements would decrease both the anorexic response to IL-1 via reduced cyclooxygenase metabolites and the production of IL 1, via altered lipoxygenase metabolites. PMID- 2193580 TI - Specificity in metabolic effects of cachectin/TNF and other related cytokines. PMID- 2193581 TI - Cytokines, acute phase proteins, and tissue injury. C-reactive protein opsonizes dead cells for debridement and stimulates cytokine production. PMID- 2193582 TI - Plasma cholesterol-lowering activity of monocyte colony-stimulating factor (M CSF). AB - We investigated the action of monocyte colony-stimulating factor (M-CSF) on plasma cholesterol metabolism. Recombinant human monocyte colony-stimulating factor (rhM-CSF) was intravenously injected into Watanabe heritable hyperlipidemic (WHHL) rabbits that were deficient in LDL receptor. The treated rabbits showed decreases in plasma total cholesterol levels from 493 +/- 39 to 416 +/- 45 mg/dl (about 15%) during the treatment. The decrease in total plasma cholesterol level was due to decreased levels of lipoproteins containing apo B 100 such as VLDL, IDL, and LDL. The effect of M-CSF on the LDL-receptor-deficient animal in vivo and evidence from Northern blot analysis of liver suggested that M CSF lowers plasma cholesterol level through activated uptake of lipoproteins containing apo B 100 via pathways other than the hepatic LDL receptor. We have started a clinical study to evaluate the plasma cholesterol-lowering effect of M CSF in patients with familial hypercholesterolemia, and have observed a decreased in total plasma cholesterol level in one of three patients treated with M-CSF. M CSF may provide new insight into plasma cholesterol metabolism and a possible new tool to treat patients with hypercholesterolemia and atherosclerosis. PMID- 2193583 TI - Effect of vitamin B6 on immunocompetence in the elderly. PMID- 2193584 TI - Vitamins and the immune system. PMID- 2193585 TI - The clinical significance of micronutrients in relation to immune functions. PMID- 2193586 TI - Micronutrient and lipid interactions in cancer. PMID- 2193587 TI - Micronutrients and immune functions. An overview. PMID- 2193588 TI - The effect of carotenoids on the antitumor immune response in vivo and in vitro with hamster and mouse immune effectors. PMID- 2193589 TI - [Langerhans cells in the physiopathology of atopic dermatitis]. AB - INTRODUCTION. Atopic dermatitis (AD), allergic rhino-conjunctivities and allergic asthma constitute the classical triad of atopic diathesis attended, in many cases, by high serum IgE levels. While the pathophysiology of IgE-mediated allergic respiratory diseases is now better understood, the pathophysiological significance of atopic phenomena in the genesis and control of AD is still far from being clear. Numerous clinical and laboratory data point to a pathophysiological relation between IgE-mediated reactions and AD, but no one yet knows by which mechanism this interaction takes place. Some recent studies suggest that Langerhans cells might well be the missing link. THE LANGERHANS CELLS. Langerhans cells (LC) are dendritic epidermal cells originating in the bone marrow and supposedly belonging to the monocyte lineage. Their circulating precursors, the mechanism of their migration into the epidermis and their relationship with other dendritic cells, such as the interdigitating follicular cells, are controverted. LC express numerous surface markers, such as class I and II HLA, CD1a, CD4 and receptors for complement and IgE Fc fragments. Under normal conditions, LC do not express IgE receptors. Ultrastructurally, LC are characterized by the presence of Birbeck granules in their cytoplasm. Among the presumed functions of LC in the skin, the best documented is the presentation of antigens to T lymphocytes in allergic contact dermatitis. LANGERHANS CELLS IN ATOPIC DERMATITIS. Quantitative studies. Modern immunohistological methods based on the reactivity of monoclonal anti-CD1a antibodies have given results that are sometimes conflicting due to differences in the quantification techniques utilized. However, morphometric enumeration of LC on cryostat sections have shown that their number is about the same in AD and in normal skin. PRESENCE OF IgE BEARING LANGERHANS CELLS IN ATOPIC DERMATITIS. The presence of IgE molecules on the LC surface has been demonstrated in subjects with AD. It must be noted that in atopic subjects IgE bearing Lc are only found in patients with high serum IgE levels. They are absent in asthma patients without eczema, irrespective of their serum IgE levels. Daily applications of corticosteroids on AD lesions result in a decrease of anti-IgE markers on LC after one week and in their complete disappearance after 2 weeks. IN ATOPIC DERMATITIS LANGERHANS CELLS EXPRESS A RECEPTOR SPECIFIC TO Fc FRAGMENTS OF IgE. The exact nature of the receptor for IgE expressed in situ in AD patients is still conjectural. Some authors have been able to demonstrate that the binding of IgE molecules by LC isolated from the skin of atopic patients is inhibited by a monoclonal antibody directed against the low affinity receptor (Fc epsilon R2) of eosinophils and macrophages. This strongly suggests that certain factors induce the expression by LC of an Fc epsilon R2 receptor. IN VITRO INDUCTION OF IgE RECEPTORS ON NORMAL LANGERHANS CELLS... PMID- 2193591 TI - [Hallermann-Streiff syndrome. A case report]. PMID- 2193590 TI - [Cutaneous manifestations of chronic familial granulomatosis. Apropos of a case]. PMID- 2193592 TI - [Malignant angioendotheliomatosis or intravascular lymphoma/angiotropic lymphoma]. PMID- 2193593 TI - [The adipose tissue of the pelvis in imaging technics]. AB - Fat is a fundamental contrast agent in pelvic imaging. The features of fat are typical on CT and MRI but vary on ultrasonography according to the physical characteristics and histology. The study of pelvic fat is of great importance in pelvic exploration because fat outlines both the normal structures and their borders. Involvement or masking of the pelvic fat is a good marker of carcinologic spread. Changes in pelvic fat may also be observe in inflammatory diseases. Specific diseases of fatty pelvic connective tissue such as lipomatosis and liposarcomas, are classically described. Teratomas with a fatty component derived from pelvic structures (ovaries) are easily diagnosed using imaging methods. PMID- 2193594 TI - [Metastasis of breast cancer in frontal meningioma]. AB - The authors report a case of metastasis from a breast cancer located in a frontal meningioma. A review of the literature revealed 43 cases of primary intracranial tumours containing a secondary from an unrelated extracranial primary malignant tumour; in 34 of these cases the intracranial tumour invaded was a meningioma. PMID- 2193595 TI - Human recombinant interleukin-2 augments porcine natural killer cell cytotoxicity in vivo. AB - Immunological parameters of porcine peripheral blood mononuclear cells after in vivo injections of human recombinant interleukin-2(125) (HrIL-2) were studied. Eighteen pigs (6 pigs/group) were injected with either 10(4) or 10(5) units/kg body weight of human rIL-2 or an equivalent volume of sterile physiological saline (control) on days 0 through 4. All pigs were immunized with an E coli J5 bacterin on day 0. Cytolytic activity to porcine fibroblasts (PK-15) was increased (P less than 0.02) in pigs treated with HrIL-2 when compared to control animals. Cytotoxicity to K-562 cells also showed a tendency (P less than 0.08) towards increased cytolytic activity in the HrIL-2-treated pigs. Lymphocyte blastogenesis, IL-2 production, and serum iron concentrations did not differ between treatment groups. Antibody concentrations to E coli J5 antigens increased significantly (P less than 0.05) in all groups after immunization, but there were no differences between treatment groups. These data suggest that in vivo injections of Hr-IL-2 increase natural cytotoxic cell activity in pigs without influencing other immune activities. PMID- 2193596 TI - Treatment of induced enterotoxigenic colibacillosis (scours) in calves by the lactoperoxidase system and lactoferrin. AB - The clinical efficacy of a preparation based on the lactoperoxidase system (LP-s) and lactoferrin (LF) was tested in calves experimentally infected with E coli K99+, Ent+. Mortality, occurrence and duration of diarrhoea were significantly lower (P less than 0.05) and general clinical status significantly better (P less than 0.05) in infected calves treated with LP-s and LF preparation than in infected but non-treated calves. Results suggest that LP-s and lactoferrin are effective in the treatment of enteric colibacillosis in calves. PMID- 2193597 TI - [Extracorporeal lithotripsy in gallbladder calculi. Results of a single-center experience of 31 patients]. AB - The authors studied thirty one cases (18 women, 13 men) of extracorporeal shock waves lithotripsy on symptomatic gallbladder stones realized with piezoelectric generators. There were one to six stones per patient with individual stone size from 8 to 40 mm; among them 16% were calcified. Any anesthesia was necessary. Shock-wave frequency was 1.25 and 2.5 Hz. The average number of shock waves administered was 4,600 per treatment. Fragmentation occurred in 67% after first treatment and in 74% after second treatment. Gallstones disappeared in 9.5% and 19.5% of patients after 6 weeks and 4 months respectively. There was no modification after four treatments in 22.5% of patients. Minor side effects were noted: back pain (29%) probably because of uncomfortable position during treatment; increased thickness of gallbladder wall (26%); biliary pain (22%). Two episodes of biliary tract obstruction by stone fragments (one mild pancreatitis, one jaundice with liver enzymes elevation) disappeared spontaneously. These results were comparable with those of other groups using the same shock waves lithotripter. PMID- 2193598 TI - [The natural history of viral hepatitis]. PMID- 2193599 TI - [Infectious esophagitis]. PMID- 2193600 TI - [Helicobacter pylori and gastric pathology]. PMID- 2193601 TI - [Bacterial ecology of the digestive tract]. PMID- 2193602 TI - [Contribution of endo-sonography in the evaluation of cancer of the esophagus]. AB - Images of endoscopic ultrasonography are compared with data of surgery and histology. As to tomodensitometry, endoscopic ultrasonography has proved to be more accurate in study of penetration into the esophageal layers, of extension to surrounding structures, specially peri-esophageal lymph nodes. In contrast, endoscopic ultrasonography is helpless searching distant lymph nodes involvement and metastases. These new imaging techniques, together with tracheo-bronchoscopy, enable high degree of precision in determination of the extent of the tumor. Despite better accuracy of the staging, surgical indications remain controversial. PMID- 2193603 TI - [Treatment of acute calculi-induced pancreatitis]. PMID- 2193604 TI - [Renal needle biopsy: a comparative study of fluoroscopic and echographic guidance]. AB - The authors report a comparative study of two renal biopsy procedures: fluoroscopic guided biopsy and ultrasound guided biopsy. Results were similar with an interpretability rate of 90%. Morbidity was found to be equal in the two group. However, ultrasound guided biopsy is superior to fluoroscopy guided biopsy in two respects: for patients with renal failure in whom IVP is not possible; for the medical team and patient, who are not exposed to radiation. PMID- 2193605 TI - [3 experimental models applied to the study of urothelial tumors of the bladder]. AB - Three important models can be used in experimental carcinogenesis: Clonogenic assays which can be used to study tumor cells in vitro. This method is particularly useful in order to investigate biochemical markers and chromosomal spreads. Chemically-induced bladder tumors in various animals are used to analyse the mechanisms of induction and development of these cancers. The athymic mice have provided, over the last twenty years, an immunological system suitable for the heterotransplantation of human tumor tissues. These three experimental models, which are complementary, are reviewed and discussed. PMID- 2193606 TI - [Treatment of hemorrhagic cystitis caused by cyclophosphamide using intravesical instillation of potassium alum. Apropos of 5 cases]. AB - Five patients with malignant hemopathies, including four treated by bone marrow transplantation, developed cyclophosphamide-induced hemorrhagic cystitis that failed to respond to the usual treatments. Each was treated by continuous irrigation of the bladder with potassium alum. Hematuria ceased in three patients followed up for 5 to 10 months. A review of the literature confirmed the 75% success rate of this treatment. No local side effects were recorded, but one patient had a single seizure. PMID- 2193607 TI - [Cancer of the testis, sarcoidosis and neurinoma]. AB - The association of testicular cancer, sarcoidosis and neuroma is reported. Review of the literature revealed the rarity of the association of testicular cancer and sarcoidosis which is probably a chance association, but which is important in the context of staging, as overstaging may lead to useless or even dangerous treatment. PMID- 2193608 TI - [Primary tumors of the upper urinary tract. Apropos of 49 cases and a review of the literature]. AB - We report 49 tumors of the upper urinary tract treated between 1980 and 1988. Intravenous pyelography with direct opacification technics gave the diagnosis in 83.7% of patients. Ultrasonography and computed tomography were only reliable for tumors of renal pelvis. Urinary cytology gave good results only in high grade invasive transitional cell carcinoma. Nephro-ureterectomy is always recommended. PMID- 2193609 TI - [Wegener's granulomatosis with urethral-penile location. Apropos of a case]. AB - The authors report a case of Wegener granulomatosis presenting as a necrotizing urethral tumor in a 44 year-old man. Involvement of the urethra by Wegener granulomatosis in unusual which explains the delay in diagnosis particularly when the urethral localization is isolated. The prognosis is severe despite urinary diversion and appropriate therapy. Five cases from the literature are reviewed. Prednisone and cyclophosphamide therapy for Wegener granulomatosis now gives dramatic results, but an urethral localization could occur in the subsequent course of the disease with the same severe prognosis. PMID- 2193610 TI - Intracranial hypertension associated with unruptured cerebral arteriovenous malformations. AB - Only 6 patients with intracranial hypertension associated with unruptured cerebral arteriovenous malformations have been reported. We report 6 additional patients seen at the Cleveland Clinic during the past 10 years. The average age was 28 years (range, 19-44 years); 4 were women. Symptoms and signs included papilledema (6 patients), headache (6), transient nonepileptic focal symptoms (4), visual obscurations (3), ipsilateral carotid or ocular bruits (3), abnormal visual fields (3), focal seizures (2), and progressive visual loss (1). Enhanced computed tomography (CT) or magnetic resonance imaging (MRI) demonstrated the malformations in all 6 patients. The malformations were large, supplied by the branches of the middle and anterior cerebral arteries, with the posterior cerebral artery contributing in 3 patients, and all drained into the superior sagittal sinus. Associated venous obstruction was seen in 2 patients. Four patients underwent excision of the arteriovenous malformation, with resolution of papilledema in all 4. Measurements of cortical arterial and venous pressures during surgery in 3 patients showed decreased feeding artery pressures and elevated draining vein pressures, which normalized after removal of the malformation. Treatment in the 2 remaining patients consisted of medical therapy (acetazolamide, furosemide, steroids) alone in 1 patient, and in conjunction with proton beam radiation in the other. Papilledema resolved in the former patient, but the patient receiving proton beam radiation still had papilledema 2 years later. Intracranial hypertension associated with unruptured cerebral arteriovenous malformations occurs in young patients with high flow malformations that drain into the superior sagittal sinus, and is likely the result of increased cortical venous and superior sagittal sinus pressure. Excision of the malformation effectively reduces the intracranial pressure. PMID- 2193611 TI - An unusual variant of Becker muscular dystrophy. AB - We report on 5 brothers with slowly progressive limbgirdle weakness. Calf hypertrophy was absent. The levels of creatine kinase, electromyography, and findings from a muscle biopsy specimen were compatible with muscular dystrophy. The propositus's biopsy specimen also showed numerous rimmed vacuoles. DNA analysis revealed a deletion in the dystrophin gene, establishing a diagnosis of Becker muscular dystrophy. Both the absence of calf hypertrophy and the presence of rimmed vacuoles are unusual features in this disorder. PMID- 2193612 TI - Therapeutic trials for multiple sclerosis. PMID- 2193613 TI - Efficacy and toxicity of cyclosporine in chronic progressive multiple sclerosis: a randomized, double-blinded, placebo-controlled clinical trial. The Multiple Sclerosis Study Group. AB - Patients with clinically definite multiple sclerosis, mild to moderately severe neurological disability (entry score on the Expanded Disability Status Scale (EDSS) between 3.0 and 7.0), and a progressive course defined by an increase in the EDSS of between 1 and 3 grades in the year prior to entry were randomized to receive either cyclosporine (n = 273) or placebo (n = 274) in a 2-year, double blinded, multicenter trial. Treatment groups at entry proved balanced for age, gender, duration of illness, and neurological disability. Cyclosporine dosage was adjusted for toxicity and a median trough whole-blood level was maintained between 310 and 430 ng/ml. The mean increase in EDSS score was 0.39 +/- 1.07 grades for cyclosporine-treated patients and 0.65 +/- 1.08 grades for placebo treated patients from entry until the time of early withdrawal or completion of the study (p = 0.002). Of three primary efficacy criteria, cyclosporine delayed the time to becoming wheelchair bound (p = 0.038; relative risk, 0.765), but statistically significant effects were not observed for "time to sustained progression" or on a composite score of "activities of daily living." Active treatment did have a favorable effect on several secondary measures of disease outcome. A large and differential withdrawal rate (44% for cyclosporine-treated patients, 32% for placebo-treated patients) complicated the analysis but did not appear to explain the observed effect of cyclosporine in delaying disease progression. Multivariate analysis did not show institutional effects but did demonstrate substantial effects of baseline neurological disability on outcome. Nephrotoxicity and hypertension were common troublesome toxicities and accounted for most of the excess loss of patients in the cyclosporine arm of the study. Thus, chronic cyclosporine therapy was associated with a statistically significant but clinically modest delay of progression of disability in a group of patients with multiple sclerosis selected for moderately severe and progressive disease. Close supervision by physicians familiar with cyclosporine is mandatory to minimize known adverse effects, particularly nephrotoxicity, when considering the use of this immunosuppressant. PMID- 2193614 TI - Net production of cerebrospinal fluid is decreased by SCH-23390. AB - A high density of binding sites for the ligands 3H-SCH-23390 and 3H-SKF-83566 has been found in the choroid plexus. Although these sites have similar pharmacology to D1 dopamine receptors, the high-affinity component of 3H-SCH-23390 binding in the choroid plexus has been identified as the 5-HT1c subtype of serotonin receptor. We investigated the possible role of these receptors in modulating the production of cerebrospinal fluid (CSF) in rats. (R) SCH-23390 produced up to a 50% decrease in net CSF production, compared to saline. This compound is a partial agonist at 5-HT1c serotonin receptors, and an antagonist at D1 dopamine receptors. The (S) enantiomer of SCH-23390 (SCH-23388) was ineffective. Drugs interacting with receptors for neurotransmitters in the choroid plexus may hold promise for the treatment of patients with increased intracranial pressure, including those with mass lesions, head trauma, acute or chronic hydrocephalus, or pseudotumor cerebri. PMID- 2193615 TI - Plasmid-mediated 4-quinolone resistance: a real or apparent absence? PMID- 2193616 TI - Patterns and mechanisms of beta-lactam resistance among isolates of Escherichia coli from hospitals in the United States. AB - To study the national distribution of beta-lactam resistance patterns and mechanisms among Escherichia coli organisms isolated in U.S. hospitals, 652 ampicillin-resistant (Am(r)) or ampicillin-intermediate (Ami) isolates were submitted to the Centers for Disease Control from March 1983 through July 1984 by nine hospitals participating in the National Nosocomial Infections Study. Among the isolates (most of which caused urinary tract infections), 78% were Am(r) and 22% were Ami by the interpretative criteria established by the National Committee for Clinical Laboratory Standards. Resistance to carboxypenicillins ranged from 73 to 74%, and that to acylureidopenicillins ranged from 43 to 66%. A total of 26% of the isolates were resistant to cephalothin, and 4% were resistant to cefazolin. Resistance to cefoxitin was 1%, while resistances to cefuroxime and cefamandole were 2 and 7%, respectively. With the exception of cefsulodin (98% resistant) and cefoperazone (1% resistant), there was no resistance to newer cephalosporins or aztreonam. In general, only minor differences in the incidence of resistance to beta-lactam antibiotics were noted in hospital-acquired versus non-hospital-acquired isolates as well as among isolates from various regions of the United States. TEM beta-lactamases were produced by 87% of the 237 Am(r) isolates examined. By our methods, OXA and chromosomal (type I) beta-lactamases were detected in 2 and 28 isolates, respectively, and plasmid-mediated extended spectrum cephalosporinases were detected in none of the isolates. Disk substrate and clavulanic acid inhibition assays revealed that TEM beta-lactamase conferred Am(r) and resistance to carboxypenicillins, acylureidopenicillins, cephalothin, cefamandole, cefsulodin, and cefoperazone. A total of 391 isolates were screened for plasmids, and 259 isolates were examined by DNA hybridization with a TEM probe. Among 462 plasmids probed, 129 plasmids, ranging from 4 to 140 megadaltons, harbored TEM sequences. Although beta-lactam resistance in clinical isolates of E. coli is predominantly mediated by TEM beta-lactamase, the diverse spectrum of resistance appears to be related to additional strain=dependent factors. PMID- 2193617 TI - Comparative effects of cilofungin and amphotericin B on experimental murine candidiasis. AB - The effectiveness of cilofungin (LY121019, referred to hereafter as LY), a lipopeptide, was studied in a murine candidiasis model. CD-1 mice (5 weeks old) were injected intravenously with 3 x 10(5) Candida albicans yeast cells. Intraperitoneal LY or amphotericin B (AmB) therapy was begun 4 days after infection and was continued daily for 2 weeks. LY and AmB were compared at 62.5, 6.25, and 0.625 mg/kg per day, with the LY dose split into two treatments per day. Mice were observed for 30 days postinfection, and survivors were necropsied. AmB at 62.5 mg/kg per day was lethal in the absence of infection. Cumulative mortality for infected controls was 94% (17 of 18). Survival of mice treated with the control diluent for LY was the same as survival with no treatment. Survival after 0.625 mg of LY per kg per day was the same as that of the controls, and 6.25 or 62.5 mg of LY per kg per day was significantly superior. AmB treatment at 0.625 or 6.25 mg/kg per day was protective and superior to the same LY doses. Atrophied kidneys were common in AmB-treated mice, and mice treated with 6.25 mg of AmB per kg per day appeared ill during therapy. The number of CFU recovered from kidneys and spleens of surviving mice reflected the same relationships between drugs and doses as those described for mortality. C. albicans was not cleared from the kidneys of mice in any group, and only in the 6.25-mg/kg-per-day AmB treatment group was not detectable C. albicans found in the spleens. These data indicate that LY or AmB suppresses candida infection but neither is curative in this model. PMID- 2193618 TI - Biochemical characterization of a beta-lactamase that hydrolyzes penems and carbapenems from two Serratia marcescens isolates. AB - Reexamination of Serratia marcescens isolates obtained in 1982 revealed two organisms that were resistant to the penem FCE 22101 (MIC, 512 micrograms/ml) and imipenem (MIC, 16 micrograms/ml) and that had slightly reduced susceptibilities to meropenem (MIC, 0.12 micrograms/ml). MICs of these agents for typical S. marcescens isolates were 1 to 8, 0.25 to 0.5, and 0.03 micrograms/ml, respectively. The two isolates were fully susceptible to broad-spectrum cephalosporins, and only one was highly resistant to ampicillin and carbenicillin (MICs, greater than 1,024 micrograms/ml). Both isolates had beta-lactamases that focused at pIs 8.2 and 9.7. The penicillin-resistant isolate additionally produced the TEM-1 enzyme. The enzymes with pIs of 8.2 and 9.7 were separated by cation-exchange chromatography. The pI 8.2 beta-lactamase was a class I enzyme of the type found in most S. marcescens isolates. It was almost inactive against carbapenems and penems, as was the class I enzyme from another S. marcescens strain. The pI 9.7 enzyme hydrolyzed penems and carbapenems rapidly: kcat (turnover number) values for FCE 22101, imipenem, and meropenem were 3.4, 26, and 1% of the kcat value for cephaloridine, respectively; kcat/Km values were 140, 915, and 150% of the kcat/Km value for cephaloridine, respectively. Otherwise, the pI 9.7 enzyme had predominantly penicillinase activity. It was inhibited more readily by clavulanate than by tazobactam and was inactivated by the chelating agents EDTA and ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. Expression of the pI 9.7 enzyme was not associated with any plasmid, and production was not transferred to Escherichia coli K-12 recipients, even after the mobilizing plasmid pUZ8 was inserted into the S. marcecens donor strains. PMID- 2193619 TI - Potentiation of susceptibility to aminoglycosides by salicylate in Escherichia coli. AB - Susceptibility of Escherichia coli to kanamycin and seven other aminoglycosides has been found to be strongly potentiated by salicylate. At pH 7.5, in the presence of 15 mM salicylate and 0.5 micrograms of kanamycin per ml, the efficiency of plating of the bacteria was 2 x 10(-5), whereas there was no significant killing in the presence of kanamycin or salicylate alone. With 0.75 micrograms of kanamycin per ml, the addition of 2.5 mM salicylate was sufficient to reduce the efficiency of plating by more than 10(4)-fold. Synergistic effects were found also at pHs 6.5 and 8.5. To determine whether the action of salicylate resulted from its behavior as a weak acid or its salicyl structure, similar experiments were carried out with acetate and salicyl alcohol. Acetate, a membrane-permeating weak acid, showed a synergistic effect on kanamycin susceptibility at pH 6.5 that was comparable to the effect seen with salicylate at pH 6.5. However, acetate had no synergistic effect with kanamycin at pH 7.5 or 8.5. This is consistent with the ability of acetate to increase the membrane potential of cells and the dependence of susceptibility to kanamycin and other aminoglycosides on the membrane potential. Salicyl alcohol, which has a hydroxyl group in the place of the carboxyl group that is present in salicylate, was an effective synergist with kanamycin. It was equally effective at pHs 6.5 and 7.5 and somewhat more effective at pH 8.5. These results support the hypothesis that two effects are involved in the synergy between aminoglycosides and salicylate: a weak acid effect, possibly to increase the membrane potential, and an uncharacterized effect related to the salicyl structure. PMID- 2193620 TI - Azole susceptibility and hyphal formation in a cytochrome P-450-deficient mutant of Candida albicans. AB - A cytochrome P-450-deficient mutant of Candida albicans, strain D10, was employed to study the mode of action of imidazole antifungal agents. This mutant accumulates exclusively 14-alpha-methylsterols, resulting in a sterol profile which mimics that of azole-treated wild-type strains. Since the widely accepted primary effect of imidazoles is the inhibition of cytochrome P-450-mediated demethylation of the ergosterol precursor lanosterol, strain D10 and its wild type revertant, strain D10R, were grown in the presence of concentrations of clotrimazole, miconazole, and ketoconazole known to inhibit demethylation. The growth of strain D10 was unaffected by these antifungal agents, while that of strain D10R was significantly reduced. At higher azole concentrations (which are known to exert a direct, disruptive action on the cell membrane), the growth of both strains was immediately and completely inhibited by clotrimazole and miconazole. Ketoconazole was membrane disruptive only for strain D10; this is the first report of a direct membrane effect for this drug. Because hyphal formation has been implicated in the pathogenesis of C. albicans and because it has been shown to be inhibited by azoles, the hypha-forming capability of strain D10 was examined. Strain D10 was shown to be seriously defective in hyphal formation, suggesting that this function may be dependent on the 14-alpha-demethylation of lanosterol. The results of this study suggest that inhibition of lanosterol demethylation per se is neither fungicidal nor fungistatic, although the growth rate is reduced. In addition, the substitution of 14-alpha-methylsterols for ergosterol results in defective hyphal formation and in a cell that is more susceptible to membrane-active agents such as ketoconazole. PMID- 2193621 TI - Purification of a glutathione S-transferase that mediates fosfomycin resistance in bacteria. AB - The enzyme that modifies fosfomycin by formation of an adduct with glutathione was purified 12-fold with a 56% activity yield by passage through DEAE Sephacel and high-performance liquid chromatography molecular exclusion columns. Its functional form was a homodimer of two 16,000-dalton polypeptides, which possibly showed an antiparallel alpha tertiary structure and which lacked marked hydrophobic regions. Visualization of the reaction was achieved by precolumn derivatization of glutathione and the adduct, separation by high-performance liquid chromatography, and fluorescence detection of both compounds. Temperature and pH optima were 20 to 30 degrees C and 8.25, respectively; Mn2+, Fe2+, and Co2+ enhanced the rate of modification; and Km values were 9.4 and 11 mM for fosfomycin and glutathione, respectively. Phosphoenolpyruvate did not interfere with fosfomycin modification. The enzyme was stable at 4 degrees C for at least 6 months but progressively lost its activity upon being heated for 60 min at temperatures over 30 degrees C. PMID- 2193622 TI - Antimicrobial susceptibility of Salmonella typhimurium carrying the outer membrane permeability mutation SS-B. AB - The antibiotic susceptibility profile of Salmonella typhimurium SS-B, a mutant susceptible to some antimicrobial agents, was studied in detail. Twenty-eight agents were tested, and eleven of these had MICs significantly lower (32- to greater than 250-fold) for the SS-B strain than for its parent. The drugs were generally hydrophobic or amphiphilic. Polymyxin B nonapeptide, which has a known outer membrane permeabilizing action, further reduced the MIC of several of these agents for the SS-B strain by a factor of approximately 10 to 30. In most cases, the resulting MICs were lower than the corresponding MICs for the parent strain grown in the presence of polymyxin B nonapeptide. In addition, the hydrophobic fluorescent probe N-phenyl naphthylamine was rapidly embedded in the membranes of the SS-B strain but was poorly embedded in those of the parent strain. PMID- 2193623 TI - Activities of beta-lactam antibiotics against Escherichia coli strains producing extended-spectrum beta-lactamases. AB - Seven extended-spectrum beta-lactamases related to TEM and four enzymes derived from SHV-1 were transferred to a common Escherichia coli host so that the activity of a variety of beta-lactams could be tested in a uniform genetic environment. For most derivatives, penicillinase activity was 10% or less than that of strains making TEM-1, TEM-2, or SHV-1 beta-lactamase, suggesting that reduced catalytic efficiency accompanied the broader substrate spectrum. Despite this deficit, resistance to aztreonam, carumonam, cefdinir, cefepime, cefixime, cefmenoxime, cefotaxime, cefotiam, cefpirome, cefpodoxime, ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, cefuroxime, and E1040 was enhanced. For strains producing TEM-type enzymes, however, MICs of carumonam, cefepime, cefmenoxime, cefotiam, cefpirome, and ceftibuten were 8 micrograms/ml or less. Susceptibilities of cefmetazole, cefotetan, cefoxitin, flomoxef, imipenem, meropenem, moxalactam, temocillin, FCE 22101, and Sch 34343 were unaffected. FCE 22101, imipenem, meropenem, and Sch 34343 were inhibitory for all strains at 1 microgram/ml or less. In E. coli an OmpF- porin mutation in combination with an extended-spectrum beta-lactamase enhanced resistance to many of these agents, but generally by only fourfold. Hyperproduction of chromosomal AmpC beta-lactamase increased resistance to 7-alpha-methoxy beta-lactams but not that to temocillin. When tested at 8 micrograms/ml, clavulanate was more potent than sulbactam or tazobactam in overcoming resistance to ampicillin, while cefoperazone-sulbactam was more active than ticarcillin-clavulanate or piperacillin-tazobactam, especially against TEM-type extended-spectrum beta-lactamases. PMID- 2193624 TI - Multicenter prospective study of treatment of Brucella melitensis brucellosis with doxycycline for 6 weeks plus streptomycin for 2 weeks. AB - The effectiveness of treating human brucellosis caused by Brucella melitensis with a 6-week course of doxcycline plus streptomycin for 2 of those weeks was analyzed by a multicenter prospective study of 139 patients. Subjects with central nervous system involvement, endocarditis, or spondylitis were excluded from the study. All but 5 of the 139 patients completed the full treatment schedule and became afebrile in the first week of therapy. Four patients suffered relapses during the follow-up period. Of the five patients who did not complete the treatment, two left because of adverse secondary effects (1.4%), another two left for noncomplicance with the treatment (1.4%), and the remaining patient was considered a therapeutic failure because his symptoms persisted after the first week of therapy (0.7%). We concluded that the combination of doxycycline and streptomycin is an effective treatment for the types of brucellosis included in our study. PMID- 2193625 TI - In vitro antibacterial activity and interactions with beta-lactamases and penicillin-binding proteins of the new monocarbam antibiotic U-78608. AB - U-78608, a new monocarbam antibiotic, was evaluated for in vitro activity against 312 clinical isolates of aerobic and anaerobic bacteria and subjected to several in vitro biochemical tests characterizing its interactions with beta-lactamases and penicillin-binding proteins (PBPs). The antibacterial activity of the compound was compared directly with those of SQ 83,360 (pirazmonam) and aztreonam. U-78608, SQ 83,360, and aztreonam had generally poor activity against gram-positive aerobic bacteria and anaerobic bacteria. U-78608 demonstrated activity primarily against gram-negative aerobic bacteria, with potency generally comparable to that of SQ 83,360. U-78608 and SQ 83,360 were less active than aztreonam for some gram-negative species; however, both compounds were 8- to 64 fold more active than aztreonam against Acinetobacter species, Pseudomonas aeruginosa, and Pseudomonas maltophilia. All three compounds resisted inactivation by several different beta-lactamases from gram-positive and gram negative bacteria. Neither U-78608 nor SQ 83,360 exhibited significant inhibition of these enzymes, while aztreonam inhibited beta-lactamases from P. aeurginosa and Klebsiella oxytoca. All three compounds exhibited strong affinity to PBP 3 of Escherichia coli and moderate to negligible affinity to the other E. coli PBPs; quantitative measurements indicated that U-78608 had greater PBP 3 affinity than either SQ 83,360 or aztreonam. PMID- 2193626 TI - In vitro antibacterial spectrum of E1040 compared with those of cefpirome and ceftazidime and disk diffusion interpretive criteria for E1040. AB - E1040 is a new parenteral cephalosporin which was tested against 690 clinical isolates and compared with cefpirome and ceftazidime. E1040 had the best activity of the three drugs against Pseudomonas aeruginosa, inhibiting 89% of strains at 8.0 micrograms/ml. E1040 demonstrated good activity against members of the family Enterobacteriaceae, including cefpirome-resistant and ceftazidime-resistant strains. E1040 also had good activity against streptococci but much poorer activity against enterococci and staphylococci. When E1040 broth microdilution and disk diffusion susceptibility test results were compared, the 30-micrograms disk was recommended, with the following tentative interpretive criteria: susceptible, greater than or equal to 18 mm (MIC, less than or equal to 8.0 micrograms/ml); intermediate, 15 to 17 mm (MIC, 16 micrograms/ml); and resistant, less than or equal to 14 mm (MIC, greater than or equal to 32 micrograms/ml). PMID- 2193627 TI - Randomized trial of doxycycline versus josamycin for Mediterranean spotted fever. AB - We undertook a randomized clinical trial comparing therapeutic efficacy of the 1 day doxycycline regimen with the 5-day josamycin regimen for Mediterranean spotted fever. All 59 patients recovered uneventfully, and results did not significantly differ between the two schedules. One-day doxycycline therapy is an effective, easy, and inexpensive treatment. Josamycin is a useful therapeutic alternative that may be particularly convenient for pregnant women and patients with a history of allergy to tetracyclines. PMID- 2193628 TI - Double-blind, randomized, controlled clinical trial of norfloxacin for cholera. AB - In a double-blind, randomized clinical trial with 78 adults with acute watery diarrhea and severe dehydration, 37 subjects were positive for Vibrio cholerae. In conjunction with rehydration therapy, 13 patients received norfloxacin, 12 received trimethoprim-sulfamethoxazole (TMP-SMX), and 12 received a placebo. Norfloxacin was superior to TMP-SMX and to the placebo in reducing stool output, duration of diarrhea, fluid requirements, and vibrio excretion. TMP-SMX was no better than the placebo. PMID- 2193629 TI - Crossover study of thalidomide vs placebo in severe recurrent aphthous stomatitis. AB - A multicentric crossover randomized trial of 100 mg of thalidomide vs placebo each for 2 months was conducted in patients with severe aphthous stomatitis of more than 6 months' duration. Seventy-three patients were included. Complete remission was obtained in 32 patients who received thalidomide and in 6 patients who received placebo. The confidence interval of the difference between the two treatments ranged from 25% to 53%. Most of the patients who did not achieve a complete remission had a dramatic improvement with regard to the number of aphthae when they were receiving thalidomide. Thirteen of 17 patients who had a complete remission while they were receiving thalidomide had a recurrence with placebo, 19 +/- 9 (mean +/- SD) days after stopping this drug. Side effects were significantly more frequent with thalidomide, especially drowsiness and constipation. We concluded that thalidomide in a dosage of 100 mg/d is an effective treatment of severe aphthous stomatitis but is not without some risk. PMID- 2193630 TI - Biochemical acantholysis provoked by thiol drugs. PMID- 2193631 TI - A randomized comparison of poly-hema and hydrocolloid dressings for treatment of pressure sores. PMID- 2193632 TI - [Study of the conditions for reproducing the processes of antibiotic biosynthesis. Determining the limiting stage of the process of mass transfer of oxygen]. AB - A theoretical method for estimating limiting stage of oxygen mass transfer is proposed. The method is based on calculation and comparison of particular resistance of separate stages of mass transfer: mass transfer through the gas liquid boundary, oxygen transport in the liquid phase, mass transfer through the liquid-cell boundary and oxygen consumption by microbial cells. With the proposed method, particular resistance was calculated and conditions for oxygen mass transfer were analyzed in the biosynthesis of sisomicin as an example. As a result the conditions for reproducibility of the process in apparatus of various size were determined. PMID- 2193633 TI - [Infectious complications and their antibacterial treatment at an oncology clinic]. PMID- 2193634 TI - [Study of the conditions for reproducing the processes of antibiotic biosynthesis. Calculating the process of sisomycin biosynthesis]. AB - Conditions were experimentally studied for reproducing sisomicin biosynthesis by up-to-down scaling. It was shown that respiration intensity as a parameter of antibiotic biosynthesis scaling-down had certain limitations connected with multistage oxygen mass transfer. The parameter could be used only when the limiting stages of oxygen mass transfer coincided. It was confirmed experimentally that it was possible to apply the previously proposed theoretical method to estimation of the limiting stage of oxygen mass transfer. PMID- 2193635 TI - Deja vu in depression research. PMID- 2193637 TI - [Modified Kirchmayr suture in comparison with the Silfverskjold folding-plasty in primary management of covered Achilles tendon rupture]. AB - There is reported about 63 cases of ruptures of the Achilles-tendon from 1969 to 1988. A comparison was made between a modificated tendon suture by Kirchmayr and its combination with the tendon plastic by Silfverskjold. This resulted into the conclusion that the anatomical reconstruction of the Achilles-tendon is sufficient for good functional results if this operation takes place primary. PMID- 2193636 TI - Effects of androgen treatment in impotent men with normal and low levels of free testosterone. AB - The relation between sexual function and serum free testosterone (fT) levels, which represent the active fraction of circulating testosterone, was evaluated. Two groups of impotent male subjects with mild hypogonadism were treated with oral testosterone undecanoate (TU); these men presented with tT/luteinizing hormone (LH) ratio and tT levels at the lower limits of normal. The first group had serum fT below 6.6 ng/ml, considered the lower normal value, according to our laboratory method, whereas the second group had normal fT limits. Administration of TU improved sexual function only in impotent men with low fT levels, but not in subjects with normal fT levels, even though the tT levels and the tT/LH ratio of the two groups were not significantly different. The results of our study suggest the presence of a minimum serum fT threshold, lying near the lower normal range, which determines the male sexual function. Moreover, serum fT levels were a more sensitive index than tT for identifying impotent men who can be successfully treated with androgens. PMID- 2193638 TI - The central nervous system and atherogenesis: role of the arterial smooth muscle cell. AB - Within the last 2-3 decades neuropsychological factors have assumed a role of importance in atherogenesis implicating a contribution from the CNS to the development of arterial lesions. Despite extensive documentation in clinical studies, little work has been performed with experimental animals which could elucidate underlying mechanisms. Employing hypothalamic stimulation (HS) to model the role of the CNS, experiments in the author's laboratory have shown that atherosclerotic lesions develop in time. Evidence is presented that the underlying mechanism is due to vasospasm associated with proliferation of intimal arterial smooth muscle cells (ASMC). Both, the vasospastic and proliferative responses may originate with the same hypothalamic signal. The vasospastic response compromises perfusion, but by injuring the vessel produces pathology which increases the resistance of the artery to further spasm. The proliferation of ASMC which provides the elements for this 'stiffening' process also helps restore the vascular tone necessary to maintain the important function of perfusion. Atherosclerosis, therefore, may represent an adaptive response to excessive spasm which in many instances has advanced too far. PMID- 2193639 TI - The natural history of atherosclerosis: an ecologic perspective. AB - Virologic findings reported in recent atherosclerosis literature may have profound implications. To assess them, we have viewed atherosclerosis in a broad biologic context and against a background of environmental, behavioral, and social change. Reasonable grounds exist, we believe, for regarding atherosclerosis as a chronic, low-grade infectious macroangiopathy which is aggravated by hypercholesterolemia and other recognized risk factors. There are probably multiple infective pathogens and transmission routes. The putative agents that initiate atherosclerosis might include ubiquitous viruses that produce clinically unapparent infections in many animal species. Pathways for their transmission to humans may include the food chain and contaminated water. Food-chain transmission may have been largely responsible for the parallel increases of meat consumption and mortality from coronary heart disease in the United States during the middle third of the century. It provides a hypothetical basis for considering thermal intervention as a heretofore unrecognized factor that may actually best account for the surprising reversal of climbing heart disease mortality rates. Improved sanitation and food hygiene as well as improvements in diet, lifestyle, and medical care may have shaped the downward mortality curve. The virus hypothesis may reconcile apparent epidemiologic conflicts and elucidate the natural history of atherosclerosis. PMID- 2193640 TI - Metformin-induced changes in serum lipids, lipoproteins, and apoproteins in non insulin-dependent diabetes mellitus. AB - Forty patients with NIDDM and hyperlipoproteinemia were selected for a 12-week double-blind placebo-controlled trial to study the effects of metformin on lipoprotein concentration and composition. A significant decrease occurred in VLDL-apo B and all lipid components of VLDL, indicating a decreased number of circulating VLDL, while LDL-apo B was unchanged. Moreover in VLDL the relative TG content increased, the cholesterol content decreased, while in LDL the TG content decreased and the cholesterol content increased, indicating a change in the particle distribution over the spectrum VLDL-IDL-LDL. The initially enhanced TG content in HDL was reduced. While a reduction in VLDL is observed together with improving glucose control irrespective of the applied method, the observed compositional changes in VLDL and LDL have not been described before and seem to be metformin-specific. PMID- 2193642 TI - New concepts in the prevention of polymer-associated foreign body infections. AB - Polymer-associated foreign body infections, especially those caused by coagulase negative staphylococci, have become a problem of increasing importance in modern medicine. Therapy of such infections is often difficult and requires in many cases the removal of a catheter or an implant. On the basis of polymer material modification alternative strategies for the prevention of foreign body infections are presented. By use of high energy radiation or glow discharge techniques polymers can be modified so that new chemical groups with potential antiadhesive or antimicrobial activities can be introduced to the polymer (surface). Another approach is the coupling or incorporation of antimicrobial agents (e.g. antibiotics) to or into polymers. Such polymer-antibiotic systems are obviously not able to prevent initial bacterial adhesion to the polymer material but can effectively eliminate already adherent bacteria from the polymer surface. PMID- 2193641 TI - Two-phase [11C]L-methionine PET in childhood brain tumors. AB - Thirteen children (1.8-15.8 years of age) with brain tumors were studied with [11C]L-methionine positron emission tomography (METPET). Patients were injected intravenously with tracer before a baseline PET scan was obtained. To assess the sensitivity of [11C]L-methionine uptake to competitive inhibition, 10 patients received oral L-phenylalanine (100 mg/kg); 1 hour later, a second METPET was obtained. Subjective assessment of [11C]L-methionine uptake closely paralleled results of quantitative examination (r = 0.81). [11C]L-methionine uptake in tumor containing brain was increased in 11 patients (mean ratio of [11C] radioactivity in tumor to normal brain: 1.5 +/- 0.57; range: 1.13-2.98). Increased tracer uptake occurred in ependymomas (3), medulloblastoma (1), and astrocytomas (5), but was less intense in low-grade tumors. L-phenylalanine reduced L-methionine uptake (25-69%) in 70% of studies. L-methionine uptake was not sensitive to competitive inhibition in brain radiation injury. Two-phase METPET is of potential value in difficult clinical situations evident in children with brain tumors, including the differential diagnosis of tumor recurrence and cerebral radiation injury. PMID- 2193643 TI - A rapid and simple method of purification of Toxoplasma gondii trophozoites originating from tissue culture for use in the indirect immunofluorescent antibody test. AB - A simple and convenient purification method for Toxoplasma trophozoites from tissue culture cells by density centrifugation is described. Separation of cells treated with formaldehyde is achieved by means of a Percoll solution with a density of 1.056 g/ml permitting removal of more than 99% of the cells and cell debris from the tissue culture. Thus highly purified trophozoites of Toxoplasma gondii raised in tissue cultures become available for serological tests, particularly for the indirect immunofluorescent antibody test. PMID- 2193644 TI - Antigens of Toxoplasma gondii recognized by sera of AIDS patients before, during, and after clinically important infections. AB - A longitudinal study of different parameters of the immune responses to Toxoplasma gondii was performed with sera of AIDS patients taken during and after clinically important Toxoplasma infections. Follow-up of patients lasted for 9 months on an average. The titres of the specific IgG and IgM antibodies were measured by an indirect fluorescent antibody test (IFAT), and the appearance of circulating antigens of Toxoplasma gondii was determined in 88 sera of 18 patients with CNS (6 cases), pulmonary (1), lymph-node toxoplasmosis (1), or asymptomatic primary infections (2), respectively. The profile of the IgG antibodies reacting with a lytic antigen originating from a pool of trophozoites of six different Toxoplasma strains were examined by means of an SDS-PAGE followed by an immunoblot. Although numerous antigen bands were recognized by the sera of patients with clinically important infections, an antigen pattern characteristic of an acute infection could not be discovered. The majority of these sera, however, recognized bands at 27 and 57 kd; proteins of these molecular weights are components of the circulating antigens. In patients without any indication of a Toxoplasma infection, small amounts of antibodies reacting with 34-38 kd antigens were detected. The results of this study demonstrate that seropositivity to Toxoplasma gondii in AIDS patients determined by routine serological methods (e.g. IFAT) may be very heterogeneous even if identical titres are found; it simply results from different combinations of various antibodies which can only be detected by the immunoblotting technique. PMID- 2193645 TI - Cultural expressions affecting patient care. AB - No course or book will be of value in nursing patients from other cultures unless the nurse uses the knowledge about these cultures provided therein along with his or her own skills of observation, to assess the cultural factors involved in the health care of each individual. Madeline M. Leininger has said that in making a cultural assessment, "We talk to the members of the family as well as the patient about their health values, beliefs, and practices. Some of the many things we explore are how they keep well, who helps them when they're sick, and what folk remedies they use". Leininger further notes (1980) that "like a flowing river, culture is the underlying force that guides people's preferences and their thinking and action patterns." Many cultures have large networks of people who help out in times of illness and stress. Dr. Leininger says, "They are expected to be caring persons; it's a culturally defined role". To understand the process of how the cultural milieu affects responses to an illness like cancer, the patient must be viewed as a member of a family. This family, in turn, is influenced by its membership in an ethnic or minority group, which defines for the family members the culturally prescribed beliefs and behaviors that are acceptable. These beliefs and behaviors form the foundation upon which these individuals view illness, as well as outline how they respond to the diagnosis and the disease itself. As nurses, we must be interested in learning about and understanding the influence that culture has on our patient care. It is hoped that the information in this article will increase your knowledge base and give you greater insight into your patients because the "need to know" will continue to grow as health care clients increasingly demand and expect both respect and the effective application of their cultural beliefs and values to their health care. PMID- 2193646 TI - An antigenic portrait of the liver during carcinogenesis. PMID- 2193647 TI - Resection of pulmonary and hepatic metastasis in the management of cancer. PMID- 2193648 TI - Acute lymphoblastic leukemia in children: an update of clinical, biological, and therapeutic aspects. PMID- 2193650 TI - [Arterial hypertension and obesity]. PMID- 2193649 TI - Cellular and molecular biological aspects of human bronchogenic carcinogenesis. AB - This is a time of rapid progress in the field of human bronchogenic carcinogenesis due to recent advances in cellular and molecular biology. Important developments over the last 10 years include establishment of methods for culturing NHBE cells under defined conditions, and molecular biological and biochemical epidemiological techniques for identifying genetic changes that are associated with malignant transformation of these cells. Most progress in defining genes associated with human carcinogenesis has been due to discoveries related to oncogenes and more recently, tumor suppressor genes. As was described in Section II.B.3.a, we now know that oncogene products serve as growth factors, growth factor receptors, and cytosolic and nuclear regulatory proteins. In addition, although the actions of putative tumor suppressor genes are less well understood, the first isolated tumor suppressor gene Rb, interacts with the products of DNA viruses which, in turn, are involved in regulation of transcription as was described in Section II.B.3.b. Thus, not surprisingly, both oncogenes and tumor suppressor genes code for classes of proteins that are known to play an important role in regulation of cell proliferation. Recently, a second gene that appears to possess tumor suppression activity (p53) has been identified on the short arm of chromosome 17 (17p). The initial data suggesting a possible tumor suppressor gene on chromosome 17p came from cytogenetic and RFLP studies associating loss of heterozygosity in the chromosome 17p13 region with tumor cells and tissues. Since the p53 gene is located in this region it was evaluated and found to be frequently or always altered in several types of tumor cells. Recently, it was determined that introduction of the wild-type p53 gene into NIH3T3 cells will inhibit subsequent malignant transformation. Thus, the preponderance of evidence now supports the hypothesis that while mutated p53 acts as an oncogene, the wild-type p53 gene codes for a tumor suppressor function. The role of balance between oncogenes and tumor suppressor genes in control of proliferation is presently an active area of investigation. As discussed, introduction of a chromosome containing a tumor suppressor gene will suppress tumorigenicity of a malignant cell line, even though that cell line possesses an active c-Ha-ras oncogene. Whether or not the level of expression of an activated oncogene is related to tumorigenicity is presently being investigated.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2193651 TI - [Streptococcus group B in the etiology of neonatal infection]. AB - Group B Streptococcus (GBS) causes maternal infections during perinatal period and serious neonatal infections. Their frequency in our country is still unknown. This study analyzed the clinical and epidemiological characteristics of 13 neonates inborn at the Instituto Nacional de Perinatologia with early or late onset group B streptococcal infection. The incidence of early onset diseases (EOGBS) was 0.7 cases/1,000 live births among 20,054 inborn, and 1 case/20,000 live births of late onset diseases. EOGBS was more common in preterm newborn (median 33.2 w), low birth weight (median 2.025 g) with several maternal risk factors. Lethality rate was 38.5% (5/13). GBS is a recent important pathogen in our institute that must be investigated in another institution of our country. Group B Streptococcus; neonatal septicemia; neonatal pneumonia. PMID- 2193652 TI - [Breast feeding and protein metabolism]. AB - During pregnancy, nutrient body reserves are accumulated, especially fat, which are later mobilized during the breastfeeding period. During the synthesis of maternal milk, the mammary tissue increases its speed to synthesize structural, catalytic and exporting proteins. Due to the above, there is also an increase in the uptake of amino acids as well as the concentration of RNA within that tissue. The demand for energy during the breastfeeding period, exceeds in calories the amount of intake by the mother, causing a loss in body mass; at the same time the exchange in protein balance seems to lead towards degradation. The demand for substrates by the breast tissue is covered by the dietary intake and by other substrates mobilized from the maternal compartments. In the case where amino acids are needed, muscles have become a source of supply. These amino acids are used in the synthesis of proteins and oxidized in order to obtain fatty acids and carbohydrates. When weaning, the muscle mass recovers the amount of proteins in an undefined amount. There is a need for more information concerning the adaptations which occur during the metabolism of proteins during breast-feeding. Breast-feeding; proteins; mammary tissue. PMID- 2193653 TI - [Water-electrolyte and acid-base imbalance. VI. Metabolic acidosis]. AB - Metabolic acidosis results from a disequilibrium between production and excretion of acid. Loss of base from the body through the gastrointestinal tract or in the urine or an increase in metabolic acid production are the three major mechanisms from which metabolic acidosis is generated. Uncomplicated metabolic acidosis is manifested by an increase in blood acidity, hypobicarbonatemia, and hypocapnea. The magnitude of these changes defines the severity wf the acidosis. It is convenient to divide metabolic acidosis into two general categories (hyperchloremic and normochloremic), based on the observed anion gap, as this serves to narrow the differential diagnosis. The normal anion gap is that amount of plasma anion not measure by routine laboratory screening that accounts for the difference between the measured sodium cation (Na+) and anions (Cl +/- HCO3-). Metabolic acidosis; causes; diagnosis; clinical manifestations. PMID- 2193654 TI - Three main components in plasma proteases and their relation to the renin angiotensin system. AB - The relation of plasma renin activity (PRA) and plasma levels of angiotensin I (AI) and II (AII) to those of various proteases, including eight endopeptidases and four aminopeptidases, was investigated in 51 normal control subjects. The multivariate study using factor analysis showed that the plasma proteases can be classified into three main components: the aminopeptidase, the plasmin, and the kinin-kallikrein. PRA and AI were related almost exclusively to the aminopeptidase component, while the AII level was related not only to the same component but also to the kallikrein-kinin component. This kind of multivariate study may help in the elucidation of the role of proteases and bioactive peptides, such as angiotensin derivatives, in essential hypertension through a comparison of multivariate relationships in controls and patients. PMID- 2193655 TI - High-level expression of complementary DNA encoding rat calmodulin in Escherichia coli. AB - We report the production and characterization of a rat calmodulin made in Escherichia coli. To express the rat calmodulin cDNA in E. coli, we have employed an expression vector containing the E. coli trp promoter and trpA terminator. The cDNA was modified so as to delete the 5' nontranslated sequence and to incorporate a consensus sequence for the E. coli ribosome-binding site. Several codons for the N-terminal amino acids were selected to fit the E. coli consensus nucleotide sequence around the translational initiation codon. After induction of expression in E. coli, rat calmodulin accounted for over 30% of total cellular proteins. About 100 mg of recombinant rat calmodulin, purified to over 90% homogeneity by extraction from bacterial lysate followed by phenyl-Sepharose column chromatography, was obtained from 1 liter of E. coli culture. This recombinant calmodulin activated rat brain cyclic AMP phosphodiesterase to the same extent as the native calmodulin purified from rat brain. These results indicate that the overproduction system of the recombinant calmodulin in E. coli facilitates the study of the structure-function relationship by site-specific mutagenesis. PMID- 2193656 TI - Nucleotide sequence of a gene which enhances the activity of glyoxalase I in Saccharomyces cerevisiae. AB - A gene whose product enhances glyoxalase I activity in yeast Saccharomyces cerevisiae cells was cloned as a 6-kbp DNA fragment in the vector YEp13. The DNA fragment was subcloned in approximately 2 kbp and its base sequence determined. An open reading frame with 318 nucleotide pairs (encoding 106 amino acids) was found. According to Northern blotting analysis, the yeast transformed with the hybrid plasmid harboring the 2-kbp fragment yielded two different transcripts. From the DNA sequence of the fragment, it is deduced that the gene product would contain seven cysteine residues, five of which would be located near the carboxy terminus of the peptide. PMID- 2193657 TI - Ultrasonography of endometrium. AB - Abdominal and particularly vaginal sonography are useful diagnostic techniques for evaluating endometrium. Endometrial thickness can be measured and the echo pattern of the different parts of endometrium analysed. During normal cycles a triple line sign is typical for the late proliferative and periovulatory phase. In the secretory phase the endometrium is echogenic and posterior enhancement of echoes can be seen. It is also useful to control the effects of hormonal treatments or the endometrium using sonography. In postmenopausal women endometrial thickness of 4-5 mm or more is abnormal and further evaluations are indicated. In endometrial cancer sonography is a reliable way to estimate myometrial invasion. PMID- 2193658 TI - Doppler findings in the fetal and uteroplacental circulation: a promising guide to clinical decisions. AB - The combination of real time and Doppler ultrasonic methods has opened up new possibilities for the study of fetal and uterine haemodynamics in humans particularly for the umbilical, uterine and fetal cerebral arteries. A pathological finding in blood velocity waveforms seems to be an early and consistent alteration which precedes other markers of chronic fetal distress. The challenges are to differentiate between fetal and uteroplacental aetiologies of chronic fetal asphyxia and to search for effective treatment of early fetal distress. Recent data on the practical value of haemodynamic studies in different perinatal complications is presented in this review. PMID- 2193659 TI - Prenatal diagnosis of single gene disorders in northern Finland. AB - Prenatal diagnosis of single gene disorders is challenging because of the multidisciplinary diagnostic approach and the genetic counselling needed. Out of 3100 pregnancies of northern Finnish women studied for early detection of congenital defects or genetic disease, 110 were at risk for and 15 were unexpectedly found to carry a fetus with a single gene disorder. Seven of the 21 diseases studied were typically representative of inherited diseases in northern Finland. The diagnostic approaches used included fetal ultrasonography, analysis of the components of the amniotic fluid, fetal enzyme analysis, fetal karyotyping for the fragile X syndrome, and fetal DNA analysis. Altogether, 50 pregnancies were found to be affected; 11 of these were continued because the diagnosis was too late for termination, and seven because the parents wanted it. Prenatal diagnosis of severe hereditary disease can be enhanced by improving the detection of pregnancies at risk, and by developing methods for earlier fetal diagnosis. PMID- 2193660 TI - Ultrasonography of the lower uterine segment after multiple caesarean sections. AB - Transvaginal ultrasonic monitoring of the lower uterine segment was performed in 15 pregnancies in which the mother had previously had three or more caesarean sections. The typical findings were thinning of the myometrium, asymmetric isthmal structures and ventral ballooning of the isthmus. An image of the other of the two isthmal fenestrations was obtained by ultrasound. The antepartum ultrasonic findings and those found at operation correlated well. Maternal antepartum symptoms, on the other hand, poorly reflected the physical state on the scarred uterine isthmus. PMID- 2193661 TI - Gonadotropin releasing hormone analogues in gynaecology. PMID- 2193662 TI - Antiprogesterone RU 486--a drug for non-surgical abortion. AB - RU 486 is the first steroidal antiprogesterone in clinical use. It acts by binding to progesterone receptor, thus blocking the effects of progesterone at the uterine level, and provoking endometrial necrosis and shedding. RU 486 can, therefore, be used to interrupt early human pregnancy. In pregnancies of up to 7 8 weeks duration, the rate of complete abortions with RU 486 has ranged from 50% to 90%. The success rate can, however, be augmented up to 95%-100% by combining RU 486 with a low dose prostaglandin. RU 486 induced abortion has been well tolerated by women and highly acceptable to them. The bleeding starts 2-3 days after RU 486 administration lasting for 12-14 days. Possible clinical uses of RU 486 include induction of menstruation, late post-coital contraception, induction of labour after intrauterine fetal death, preoperative cervical ripening and treatment of progesterone receptor positive mammary tumours. When administered in the follicular phase of the cycle, RU 486 inhibits follicular development. In addition, the antiglucocorticoid properties of RU 486 have been used in symptomatic treatment of hypercortisolemia of Cushings disease. The pharmacokinetics of RU 486 are characterised by high micromolar serum concentrations, long half-life of 26-48 hours and substantial metabolism after oral administration. Although effective and well tolerated, RU 486 has aroused great moral controversy, which is currently hampering further testing and distribution of the drug. So far RU 486 has been accepted for termination of pregnancy in France and in the Peoples Republic of China, to be used with prostaglandins and under strict medical surveillance. PMID- 2193663 TI - Endometriosis and infertility. AB - The relationship of endometriosis, the most common benign gynaecological disease during reproductive life, to infertility is generally ill understood. The association between infertility and minimal to mild endometriosis, when no anatomical defect is evident, may be explained by the following possible mechanisms: alternations in peritoneal fluid (macrophages - immunoglobulins, Interleukin-1, protease inhibitors, prostanoids, an ovum capture inhibitor), ovulatory dysfunctions (anovulation, LUF syndrome), luteal phase defect, disturbed implantation, and spontaneous abortion. These possibilities are discussed. The latest prospective controlled studies offer strong evidence that endometriosis per se is not a direct cause of infertility. On the other hand, the disease usually deteriorates if not treated, and therefore medical or surgical interventions are often needed when expectant treatment or other infertility therapies, e.g., ovulation induction, fail to result in pregnancy. Women with minimal to mild endometriosis only should be diagnosed as having unexplained infertility, which today may be treated by in vitro fertilization. PMID- 2193664 TI - Hirsutism: definitions and etiology. AB - Hirsutism as a sign of hyperandrogenism is a common endocrinological disorder in women. Its spectrum varies from mild forms with dominating psychic component to severe forms associated with virilization. The severity should be assessed by semiobjective scoring systems, the use of which also allows the systematic follow up of the results of treatment. An increase in serum androgen levels or an increased turnover of androgens can be detected in most patients. Enhanced peripheral conversion of androgens to locally acting androgen also leads to hirsutism. The thorough investigation of the endocrinological milieu is required to rule out androgen producing neoplasms. In most patient, however, disturbances are functional, among which polycystic ovary syndrome is the commonest. It is a disorder exhibiting a complexity of changes in endocrinological interactions. Besides inappropriate gonadotropin secretion insulin and insulin like growth factor are also involved. The opioidergic system also seems to be affected. Polycystic ovary syndrome is also associated with obesity and infertility, both of which require attention. PMID- 2193665 TI - Bilateral bronchial anastomosis in double lung and heart-lung transplantations. AB - During heart-lung or double lung transplantation, the airway anastomosis is usually made at the tracheal level. Healing of this anastomosis is one source of postoperative complications especially after double lung transplantation (DLT). In this series of 10 patients with cystic fibrosis undergoing DLT, the tracheas of donor and recipient were anastomosed with omental wrapping in 2 cases while the two main stem bronchi were joined without omental wrapping in 8. Endoscopy disclosed no sign of ischaemia in the patients with bilateral bronchial anastomoses. Three patients died on day 20, 21 and 35, respectively, after DLT. Two of these patients (one with a tracheal and the other with bronchial anastomoses) showed no complication at the level of the suture line. The third patient (with bronchial suture) suffered dehiscence of both anastomoses which was attributed to a misdosage of corticosteroids. Of the 6 patients alive after bronchial anastomosis, 3 recovered uneventfully and 3 who had required prolonged postoperative mechanical ventilation developed bronchomalacia. Bronchomalacia was treated by laser resection and stenting. Dehiscence did not occur in any of these six cases. This technique was based on the findings of 12 fresh cadaver dissections showing that collaterals between the bronchial arteries and the pulmonary arteries and veins extend up to the origin of the main stem bronchus. Bronchial suture without omental wrap may be used for double lung and heart-lung transplantation instead of tracheal suture. PMID- 2193666 TI - [The neuromuscular junction: morphofunctional correlation]. PMID- 2193667 TI - [Polyneuropathy associated with osteosclerotic myeloma. Excellent response to chemotherapy]. AB - We report a 36-year-old patient with progressive tetraparesis and diffuse osteosclerotic lesions without secretion of a monoclonal component, in whom a diagnosis of non-secreting diffuse osteosclerotic myeloma with POEMS syndrome was made with open rib biopsy. We discuss the clinical, biological, radiological and electrophysiological features of this patient. We analyze the possible pathogenesis of his neurological involvement, with a detailed review of the relevant literature. Finally, we underline the therapeutic success with a combination of cyclophosphamide and prednisone, comparing it with the previous references to this therapeutic modality, and emphasize the validity of our therapeutic approach. PMID- 2193668 TI - [Normotensive hydrocephalus. Selection of patients for diversion treatment. Current status of the problem]. PMID- 2193669 TI - [Locked-in syndrome of reversible clinical course]. AB - A 72-year-old female developed a "locked-in" syndrome due to bilateral ventral pontine infarction. The symptoms improved 72 hours after the beginning of the clinical features. At the end of the acute phase of the disease, only a pseudobulbar syndrome of pontocerebellar type persisted. Usually, the evolution of "locked-in" syndrome is irreversible. However, our case shows that a satisfactory outcome can be possible, with a partial regression of the initially established neurological symptoms. PMID- 2193670 TI - Efficacy of inhaled tobramycin in cystic fibrosis. PMID- 2193671 TI - Recurrent tracheo-oesophageal fistula: experience with 24 patients. AB - Over an 11 year period, 275 infants with oesophageal atresia and tracheo oesophageal fistula were treated. Of these, 22 (8%) developed a recurrent fistula. An additional two patients with an established recurrent fistula were referred for secondary surgery. Infants who develop respiratory symptoms associated with feeding following repair of an oesophageal atresia should be investigated urgently with cine-radiography and/or bronchoscopy. Once the diagnosis of a recurrent fistula has been firmly established, operative repair should be undertaken. In our series of 24 patients, there were three deaths (12.5%), four patients developed a second recurrence (16.6%), while a secondary oesphageal replacement was carried out on five patients. PMID- 2193672 TI - An alternative approach to pyogenic hepatic abscess in childhood. AB - Childhood pyogenic hepatic abscess is rare and remains a difficult diagnostic problem. Seven cases in six children were treated over a 13 year period. There was a recurrence in one patient 7 years after the first presentation. Four patients had identified predisposing factors, namely, chronic granulomatous disease, acute appendicitis, previous abdominal surgery and umbilical vein catheterization, while the other two were cryptogenic. There were no specific symptoms and signs but the combination of unexplained pyrexia, upper abdominal tenderness, hepatomegaly and leucocytosis should raise the suspicion of hepatic abscess. Four cases were diagnosed by ultrasound, one by radionuclide scan and the other two at laparotomy. Treatment in the earlier years was by transabdominal drainage. In the later part of the series, percutaneous catheter drainage using ultrasound guidance was achieved with satisfactory result. Ultrasonography can provide an early diagnosis and effective treatment can be achieved with percutaneous catheter drainage in combination with appropriate antibiotic therapy. PMID- 2193673 TI - Serum IgG and IgA antibodies specific to Epstein-Barr virus capsid antigen in a longitudinal study of human immunodeficiency virus infection and disease progression in homosexual men. AB - A longitudinal study of serum IgG and IgA antibody titers to Epstein-Barr virus (EBV) viral capsid antigen (VCA) was carried out in 218 homosexual men at various stages of human immunodeficiency virus (HIV) infection. The serum samples tested were obtained from the following groups: 24 HIV seroconverters, 41 persistently HIV-seropositive asymptomatic individuals, 22 seropositives who developed AIDS related complex (ARC), 29 HIV seropositives who developed lymphadenopathy syndrome (LAS), 35 HIV seronegatives with LAS, 36 asymptomatic HIV seronegatives, and 31 AIDS patients. Blind-tested samples were titrated for IgG and IgA EBV-VCA antibodies by immunoperoxidase assay (IPA). Cross-sectional analysis indicated that all HIV-seropositive subjects exhibited significantly elevated EBV IgG and IgA antibody titers compared with HIV-seronegative subjects. The proportions with EBV-VCA IgA antibodies at a titer of greater than or equal to 128 rose during the course of HIV infection and progression of the disease: 8% in HIV seronegatives, 11% in HIV seronegatives with LAS, 25% in HIV seronegatives prior to HIV seroconversion, 44% in asymptomatic HIV seropositives, 34% in LAS, 50% in ARC, and 58% in AIDS patients. An increase in EBV-VCA IgG and IgA titers was detected following HIV seroconversion and in samples obtained 6 months before disease progression to LAS. These data suggest the possible involvement of EBV in the natural history of HIV infection and disease progression. The possibility that EBV-VCA IgA antibody levels would be of value in prediction of progression of HIV related illness is discussed. PMID- 2193674 TI - 'Ki Aikido: a solution to stress'. PMID- 2193675 TI - 'DIY dentures!'. PMID- 2193676 TI - Prognostication of survival in hospice care. AB - In summary, based on this review of the literature, the following conclusions are offered: Prognostication of survival for the terminally ill cancer patient is an inexact science. Utilization of a performance scale such as the Karnofsky scale may be helpful both in the initial as well as the ongoing assessment of prognosis. PMID- 2193677 TI - How hospices finally got a rate increase: odyssey of the 1989 Omnibus Budget Reconciliation Act. PMID- 2193678 TI - Hospice: approaching the 21st century. PMID- 2193679 TI - Empowerment for hospice. PMID- 2193681 TI - Hospice day care network. PMID- 2193680 TI - A letter to hospice board members. Medicare certification: the good, the bad, and the ugly. PMID- 2193682 TI - [Pharmacology: the last medical science]. PMID- 2193683 TI - [Have a showdown with fellow ideologists. From the history of the Norwegian Nurses' Association]. PMID- 2193684 TI - Cloning of a gene that encodes a new member of the human cytotoxic cell protease family. AB - A family of unusual serine proteases that are believed to be involved in the effector mechanism of cell-mediated cytotoxicity have previously been described in the mouse. However, in the human only one gene encoding a member has been isolated. By use of a mixture of murine cDNAs as probes, a second human gene has now been isolated. The primary structures of the gene and the predicted protein are very similar to those of the mouse. In addition, in keeping with the postulated involvement in cytolysis, transcripts were detected only in cytotoxic cells. The organization of the coding and noncoding regions of the gene, the clustering of family members, and the chromosomal location, close to the alpha chain of the T cell antigen receptor, are all conserved between human and mouse. PMID- 2193685 TI - Three-dimensional solution structure of the reduced form of Escherichia coli thioredoxin determined by nuclear magnetic resonance spectroscopy. AB - The three-dimensional solution structure of reduced (dithiol) thioredoxin from Escherichia coli has been determined with distance and dihedral angle constraints obtained from 1H NMR spectroscopy. Reduced thioredoxin has a well-defined global fold consisting of a central five-strand beta-sheet and three long helices. The beta-strands are packed in the sheet in the order beta 1 beta 3 beta 2 beta 4 beta 5, with beta 1, beta 3, and beta 2 parallel and beta 2, beta 4, and beta 5 arranged in an antiparallel fashion. Two of the helices connect strands of the beta-sheet: alpha 1 between beta 1 and beta 2 and alpha 2 between beta 2 and beta 3. Strands beta 4 and beta 5 are connected by a short loop that contains a beta bulge. Strands beta 3 and beta 4 are connected by a long loop that contains a series of turn-like or 3(10) helical structures. The active site Cys-Gly-Pro-Cys sequence forms a protruding loop between strand beta 2 and helix alpha 2. The structure is very similar overall to that of oxidized (disulfide) thioredoxin obtained from X-ray crystal structure analysis but differs in the local conformation of the active site loop. The distance between the sulfurs of Cys 32 and Cys 35 increases from 2.05 A in the disulfide bridge to 6.8 +/- 0.6 A in the dithiol of reduced thioredoxin, as a result of a rotation of the side chain of Cys 35 and a significant change in the position of Pro 34. This conformational change has important implications for the mechanism of thioredoxin as a protein disulfide oxidoreductase. PMID- 2193686 TI - Protein surface charges and Ca2+ binding to individual sites in calbindin D9k: stopped-flow studies. AB - The kinetics of calcium dissociation from two groups of site-specific mutants of calbindin D9k--a protein in the calmodulin superfamily with two Ca2+ sites and a tertiary structure closely similar to that of the globular domains of troponin C and calmodulin--have been studied by stopped-flow kinetic methods, using the fluorescent calcium chelator Quin 2, and by 43Ca NMR methods. The first group of mutants comprises all possible single, double, and triple neutralizations of three particular carboxylate groups (Glu-17, Asp-19, and Glu-26) that are located on the surface of the protein. These carboxylates are close to the two EF-hand calcium binding sites, but are not directly liganded to the Ca2+ ions. Conservative modification of these negative carboxylate side chains by conversion to the corresponding amides results in a marked reduction in the Ca2+ binding constants for both sites, as recently reported [Linse et al. (1988) Nature 335, 651-652]. The stopped-flow kinetic results show that this reduction in Ca2+ affinity derives primarily from a reduction in the Ca2+ association rate constant, kon. The estimated maximum value of the association rate constant (kon(max) for Ca2+ binding to the wild-type protein is ca. 10(9) M-1 s-1. In contrast, for the mutant protein with three charges neutralized the maximum association rate constant is estimated to be only 2 X 10(7) M-1 s-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2193687 TI - Fluid mechanics and biorheology. PMID- 2193688 TI - Further investigations of red cell deformability with nickel mesh. AB - Although the filtration method has been widely employed in red cell deformability studies, the structural irregularity of the pores of a Nuclepore polycarbonate membrane has always been a major problem. Anegawa, T. et al. (Clin. Hemorheol., 7, 1987) obtained a higher reproducibility with the filtration method using a newly designed thin metal film with pores engraved by the photofabrication technique. We further studied the pressure - flow rate relationship of red cell suspension employing this nickel mesh. The filtration of red cell suspensions through the nickel mesh was not influenced by leukocytes contamination or added leukocytes up to a leukocyte count of 250 cells/mm3 within an experimental limitation. On the other hand, the flow was greatly influenced by leukocytes contamination when the polycarbonate membrane was used. The nickel mesh was found to be useful in detecting major determinants of red cell deformability, such as cell geometry and internal cellular viscosity, and in detecting abnormalities of red cell deformability in a patient with microangiopathic hemolytic anemia. In conclusion, the present study clearly shows that the nickel mesh is preferable for investigating red cell deformability to the polycarbonate membrane from a quantitative point of view. This material should contribute to the physiologic and clinical investigation of red cell deformability. PMID- 2193689 TI - Actions of cocaine on rat nucleus accumbens neurones in vitro. AB - 1. Intracellular recordings were made from 103 neurones of the rat nucleus accumbens in vitro. 2. Dopamine (3-100 microM; in sulpiride, 1 microM) hyperpolarized neurones (79%) by acting at D1 receptors: dopamine (3-100 microM; in SCH23390, 1 microM) depolarized neurones (55%) by acting at D2 receptors. 5 Hydroxytryptamine (1-100 microM) depolarized 86% neurones. 3. Both actions of dopamine as well as the effect of 5-hydroxytryptamine were potentiated by cocaine (0.3-30 microM), which had no effect of its own on membrane potential. 4. Dose ratio was computed as [(concentration of agonist causing a 4 mV potential change in cocaine)/(concentration of agonist causing a 4 mV potential change without cocaine)]. Cocaine (1-30 microM) caused the same dose-ratio whether dopamine depolarizations (D2) or hyperpolarizations (D1) were measured; the dose-ratio ranged from 2 (1 microM) to 50 (30 microM). 5. Responses to 5-hydroxytryptamine were increased more than responses to dopamine; cocaine 1 microM gave a dose ratio of 13.4 and at 30 microM gave a dose-ratio of 118. 6. It is concluded that cocaine acts to inhibit the uptake of dopamine and 5-hydroxytryptamine in slices of rat nucleus accumbens; lower concentrations of cocaine (0.3 to 1 microM) are particularly effective in potentiating the action of 5-hydroxytryptamine. PMID- 2193691 TI - Management of personal bibliographic reference using a simple database program. PMID- 2193690 TI - Synergistic internal carotid vasodilator effects of human alpha-calcitonin gene related peptide and nimodipine in conscious rats. AB - 1. In a first series of experiments, male Long Evans rats were chronically instrumented for the measurement of internal carotid blood flow and systemic arterial blood pressure; cardiovascular changes were assessed during and after 30 min infusions of human alpha-calcitonin gene-related peptide (CGRP) (0.06 and 0.6 nmol h-1), or nimodipine (60 and 600 nmol h-1) or human alpha-CGRP plus nimodipine. The effects of human alpha-CGRP or nimodipine on internal carotid vasoconstriction induced by endothelin-1 were also measured. 2. Human alpha-CGRP (0.06 nmol h-1) caused a small (+15%), transient increase in internal carotid blood flow and a tachycardia (+33 beats min-1), but no change in mean blood pressure. Nimodipine (60 nmol h-1) caused a brief internal carotid hyperaemia (+16%) but no changes in blood pressure or heart rate. However, concurrent administration of human alpha-CGRP (0.06 nmol h-1) and nimodipine (60 nmol h-1) caused a sustained increase in internal carotid blood flow (+40%) unaccompanied by significant changes in heart rate or blood pressure. 3. Human alpha-CGRP at a dose of 0.6 nmol h-1 or nimodipine at a dose of 600 nmol h-1 caused substantial reductions in internal carotid vascular resistance (-43 and -40%, respectively); concurrent administration of these doses did not have an additive vasodilator effect. 4. Infusion of endothelin-1 (1.2nmolhV1) for 20min caused incremental constriction of the internal carotid vascular bed; human alpha-CGRP infusion (0.6 and 6.0nmolh-1) begun tOmin after the onset of endothelin-1 infusion reversed this effect (dose-dependently); nimodipine (600nmolh-1) also caused a substantial attenuation of the effects of endothelin-1. 5. In a second series of experiments the haemodynamic effects of human alpha-CGRP and/or nimodipine were assessed in rats chronically instrumented for the measurement of renal, superior mesenteric and hindquarters blood flow together with systemic arterial blood pressure. 6. Administration of human alpha-CGRP (0.06 nmol h-') alone or in conjuction with nimodipine (60nmolh-1) had no significant effects on renal or superior mesenteric vascular resistances, although there was a slight hindquarters vasodilatation. Human alpha-CGRP at a dose of 0.6 nmol -1 caused hypotension, tachycardia and reductions in renal and superior mesenteric blood flows, together with a marked (+31% maximum) hindquarters hyperaemia. Nimodipine at a dose of 600 nmol h-1 caused hypotension, tachycardia and a reduction (-34%) in renal blood flow; mesenteric blood flow was unchanged and there was an increase in hindquarters flow (+ 59%). 7. Concurrent administration of human alpha-CGRP (0.6 nmol h 1) and nimodipine (600 nmol h') did not have an additive hypotensive effect or an enhanced hindquarters hyperaemic effect, but was associated with a marked impairment of renal blood flow (-48%). 8. The present results indicate that concurrent administration of low doses of human alpha-CGRP and nimodipine might be particularly helpful in the acute treatment of patients with cerebral vasospasm and impaired renal perfusion, since this intervention improved internal carotid blood flow without compromising blood flow to the kidney. PMID- 2193692 TI - Identification of consensus patterns in unaligned DNA sequences known to be functionally related. AB - We have developed a method for identifying consensus patterns in a set of unaligned DNA sequences known to bind a common protein or to have some other common biochemical function. The method is based on a matrix representation of binding site patterns. Each row of the matrix represents one of the four possible bases, each column represents one of the positions of the binding site and each element is determined by the frequency the indicated base occurs at the indicated position. The goal of the method is to find the most significant matrix--i.e. the one with the lowest probability of occurring by chance--out of all the matrices that can be formed from the set of related sequences. The reliability of the method improves with the number of sequences, while the time required increases only linearly with the number of sequences. To test this method, we analysed 11 DNA sequences containing promoters regulated by the Escherichia coli LexA protein. The matrices we found were consistent with the known consensus sequence, and could distinguish the generally accepted LexA binding sites from other DNA sequences. PMID- 2193693 TI - Health of Alaska Natives around the time of European contact. PMID- 2193694 TI - Health and disease in the history of Alaska Natives. PMID- 2193695 TI - From Shamans to curators: bearers of tradition. PMID- 2193696 TI - Directory of museums and archives of Alaska. PMID- 2193697 TI - Socioeconomic significance of the HAP group. AB - An overview is presented of some members of the HAP group important in animal disease. An attempt has been made to highlight the economic importance of these diseases and to alert us to the importance of research that will lead to their prevention and control. PMID- 2193698 TI - Overview of the virulence attributes of the HAP-group of bacteria. AB - The pathogenicity requirements of the HAP bacteria include colonization of mucous surfaces, invasion of the host tissues, survival and multiplication in the host, interference with the defences of the host, and damage to the host. For these purposes the bacteria possess adhesion structures, capsular polysaccharides, surface structures such as outer membrane proteins, and lipopolysaccharides. They also secrete extracellular products, including exotoxins. The information available in this context for the major pathogens of the HAP group is reviewed. PMID- 2193699 TI - Capsules and virulence in the HAP group of bacteria. AB - Many species in the genera Haemophilus, Actinobacillus, and Pasteurella produce serotype-specific, negatively-charged, polysaccharide capsules. In pure form, these capsules are nontoxic, relatively inert biologically, and some are poorly immunogenic. The capsule forms the outer-most surface of the bacterium, and prior to the development of specific antibody, inhibits the bactericidal and opsonic activity of normal serum. In contrast, noncapsulated isogenic mutants are generally avirulent, and are quickly cleared by host defenses. In conjunction with the bacterial cell, or through covalent conjugation to a protein carrier, relatively high titers of antibody to capsule can be produced in immunocompetent hosts. For some pathogens (such as H. influenzae type b) antibody to capsule alone is bactericidal, opsonic, and adequate for complete protection against disease. For pathogens that produce potent exotoxins, however, (such as P. haemolytica and A. pleuropneumoniae) antibody to capsule alone may provide only partial protection. The composition or structure of the capsule may also influence the relative virulence of a particular organism. Molecular analysis of the interaction between capsules and host defenses will be required to understand more fully how capsules influence bacterial virulence. PMID- 2193700 TI - Virulence attributes of the liposaccharides of the HAP group organisms. AB - The pathogenic potential of purified gram-negative bacterial endotoxin is well documented. However, the role of endotoxin in the disease producing ability of pathogenic organisms, including those of the HAP group, remains in doubt. Endotoxin is not a classic virulence factor, but likely contributes to the pathogenic potential of gram-negative bacteria by activation of host defensive systems which ultimately results in the clinical signs and tissue damage that we recognize as disease. On the other hand, the proinflammatory nature of endotoxin, as well as liposaccharide antigens, play a critical role in the successful elimination of the infecting organism. How the induction of host defensive systems by endotoxin might benefit the infecting organism is difficult to reconcile. In this regard, host response to endotoxin often appears to be in excess of that necessary to clear the infection. Regardless of the role endotoxin might play in the pathogenesis of an infection, liposaccharide antigens are important in the serologically based classification of bacterial strains, are known to contribute to protective immunity, and are useful in the serological diagnosis of infection. PMID- 2193701 TI - Molecular characterization of cytotoxins produced by Haemophilus, Actinobacillus, Pasteurella. AB - The leukotoxin of Pasteurella haemolytica has been implicated as one of the major virulence factors contributing to the pathogenesis of bovine pneumonic pasteurellosis. To gain a better understanding of the various biochemical, antigenic and toxigenic properties of the toxin, the genetic determinant (lkt) which encodes the leukotoxin has been cloned from P haemolytica serotype 1. Results from the molecular characterization of this determinant showed that four genes are required to synthesize and secrete the active toxin from P. haemolytica. This information provides the basis for genetic manipulation of the determinant to produce different "forms" of the leukotoxin for various studies. In addition, lkt was found to be homologous to the alpha-hemolysin determinant (hly) of Escherichia coli, Proteus vulgaris, P. mirabilis and Morganella morganii. Further evidence is being accumulated demonstrating the presence of the lkt/hly determinant in several species of Actinobacillus and Haemophilus. This suggests the wide dissemination of the lkt/hly determinant in many pathogenic bacteria and established the family of Rtx cytotoxins. PMID- 2193702 TI - Interactions of Haemophilus-Actinobacillus-Pasteurella bacteria with phagocytic cells. AB - The Haemophilus-Actinobacillus-Pasteurella (HAP) group of bacteria contains a number of important veterinary and human pathogens. Although each species has specific characteristics and host range, most share the general property of being resistant to cellular defense mechanisms. In some cases (e.g. Pasteurella multocida, Pasteurella haemolytica and Actinobacillus pleuropneumoniae) resistance results in part from the presence of an antiphagocytic capsule that protects the bacilli against ingestion by neutrophils and macrophages. In other instances the bacteria aggressively attack mononuclear and polymorphonuclear phagocytes. For example, P. haemolytica, A. pleuro-pneumoniae and Actinobacillus actinomycetemcomitans each produce a leukotoxin that functionally impairs, and ultimately kills, leukocytes from cattle, pigs and human beings, respectively. Components of Pasteurella multocida and Haemophilus somnus have also been reported to adversely affect leukocyte functions. Another important area of research that is just emerging concerns the ability of lipopolysaccharide and other components of HAP bacteria to stimulate or modulate macrophage release of inflammatory mediators such as interleukin-1. In this paper, we provide an overview of the interactions of HAP bacteria with phagocytes and identify some of the common strategies by which they evade cellular defenses. PMID- 2193703 TI - Positive and negative aspects of host immune response to Haemophilus, Actinobacillus and Pasteurella. AB - Haemophilus somnus, Actinobacillus pleuropneumoniae and Pasteurella haemolytica are economically important bacteria with pathogenic characteristics that require us to look further than killed, whole cell bacterins for induction of a protective immune response. A strong immune response is not synonymous with protection and the extreme specificity of the immune response works to our disadvantage when broad protection is needed. Detection of animals that are susceptible or immune to infection is important for the purpose of diagnosis and epidemiological study. However serum antibody levels are rarely indicative of protection unless it is known that the antibody of a particular isotype must be directed against a specific epitope for protection to occur. Parenteral vaccination with killed, whole cells of H. somnus, A. pleuropneumoniae or P. haemolytica produces, respectively, adequate protection, partial protection and increased disease. The reasons for these differences and methods of improving protection, based on an understanding of virulence determinants, are discussed. PMID- 2193704 TI - Molecular aspects of the virulence of Pasteurella multocida. AB - Molecules important to the virulence of all Pasteurella multocida are little known, but much has been learned of isolates causing atrophic rhinitis of pigs. A protein toxin purified from P. multocida or from a recombinant Escherichia coli reproduces atrophic rhinitis and leads to a reduction in weight gain; antitoxin is completely protective. Toxin is important for P. multocida colonization, especially in the presence of the Bordetella bronchiseptica cytotoxin. The P. multocida toxin binds rapidly to embryonic bovine lung cells in vitro leading to an alteration of cell shape without the metabolic and structural changes associated with other toxins. This indicates a novel biochemical mechanism. However, other work suggests a subunit mode of action structurally like hormones and other bacterial toxins. PMID- 2193705 TI - Actinobacillus pleuropneumoniae: molecular aspects of virulence and pulmonary injury. AB - Contributions made by several laboratories in the area of Actinobacillus pleuropneumoniae virulence and its relationship to pulmonary disease will be reviewed briefly. Lung injury and subsequent disease, after infection with A. pleuropneumoniae, can be related to various bacterial toxins and host factors. Similar to other gram-negative bacteria. A. pleuropneumoniae has cell wall lipopolysaccharides which have been incriminated in a wide variety of toxic and tissue damaging processes. Virulent isolates of A. pleuropneumoniae have been shown to have a thick capsule whereas some avirulent isolates have a thin and easily removed capsule. The capsule of A. pleuropneumoniae is a linear unbranched polysaccharide composed of repeating dissaccharide subunits that bestow antiphagocytic properties to the bacterium but are also immunogenic. In addition, A. pleuropneumoniae has several chemically defined exotoxins. These toxins have generally been shown to be proteinaceous molecules that are hemolytic, cytotoxic, or edemogenic. Some of these toxins are proteolytic and others have the putative activity of being lytic for secretory IgA. Several of these molecules are capable of inducing lesions that are similar to those observed in natural infections and disease. Endogenous host factors have also been implicated in the development of lung lesions after infection by A. pleuropneumoniae Coagulation and inflammatory pathways have been demonstrated to be pivotal in the early phases of lesion development. In addition, the immune status of the animal is clearly related to the severity and ultimate outcome of A. pleuropneumoniae infection. To adequately treat and prevent this disease, we must understand the distinguishable interactions that occur between the host and the various molecular virulence attributes of A. pleuropneumoniae. PMID- 2193706 TI - Molecular aspects of some virulence factors of Haemophilus somnus. AB - Several virulence factors of Haemophilus somnus have been investigated, but to a varying extent. It is known that some isolates are more virulent than others. Factors associated with virulence include attachment to vaginal epithelial cells, turbinate cells or embryos; serum resistance; growth stimulation by normal flora; interference with phagocyte function; Fc receptors; and toxicity for several bovine cell types. Lipooligosaccharide and Fc receptors have been investigated at the molecular level and studies are in progress to relate their molecular structure to virulence. PMID- 2193708 TI - New diagnostic techniques: a review of the HAP group of bacteria. AB - Pasteurella haemolytica, Pasteurella multocida, Haemophilus somnus, Haemophilus parasuis and Actinobacillus pleuropneumoniae cause considerable economic loss in the cattle and swine industries. The literature relating to diagnostic procedures for these infections is reviewed. Both conventional and newer techniques are appraised in relation to the identification and classification of isolates, and to serological testing. PMID- 2193707 TI - Haemophilus influenzae: surface antigens and aspects of virulence. AB - Haemophilus influenzae type b is a major cause of bacterial meningitis and other invasive diseases in children under four years of age. One surface antigen, the type b capsular polysaccharide, polyribosylribitol phosphate (PRP), is a primary virulence factor of the organism. Antibody directed against PRP is protective; however, the purified polysaccharide is poorly immunogenic in young children. Polysaccharide-protein conjugate vaccines have been prepared which are significantly more immunogenic and efficacious in young children compared to the plain polysaccharide vaccine. Noncapsular surface antigens may also play a role in the virulence of H. influenzae. Some mutants (or phase variants) which differ in lipooligosaccharide (LOS) structure exhibit decreased virulence in the infant rat model of bacteremia. Proteins including the IgA protease, pili, a 98K outer membrane protein (OMP) as well as OMPs P1, P2 and P6 have also been examined in considerable detail, but whether they have a role in the virulence of the organism remains to be determined. However, antibody directed against the 98K OMP as well as P1, P2 and P6 is protective in the infant rat model of bacteremia. The role of antibody directed against LOS epitopes in protection is less clear, due at least in part, to phase variation in LOS antigens. Characterization of one surface antigen of H. influenzae type b, the capsular polysaccharide, already has led to the prevention of many cases of Haemophilus disease. Characterization of the noncapsular antigens together with a more detailed understanding of the mechanisms of virulence, most likely will permit development of even better vaccines, and possibly better treatment modalities, in the future. PMID- 2193709 TI - Haemophilus, Actinobacillus, Pasteurella: mechanisms of resistance and antibiotic therapy. AB - Clinical isolates of members of the family Pasteurellaceae show resistance to drugs used for therapy of common infectious diseases of animals. Veterinarians want to use an antimicrobial that is effective against the pathogen, continues to provide therapy for several days, and is not too expensive. Resistant bacteria have complicated the problem of selecting the best antibiotics for treatment of livestock. Resistance to some antibiotics, such as those which inhibit ribosome function, may be encoded on the chromosome; however most antibiotic resistance that involves enzymatic pathways is mediated by genetic elements encoded on plasmids and/or transposons. Members of the genera Haemophilus, Actinobacillus and Pasteurella contain transferable plasmids and transposons that confer antibiotic resistance. This means that clones of pathogenic Pasteurellaceae have antibiotic resistance that fluctuates due to transferable plasmids as well as more permanent resistance mediated by chromosomal changes. Effective therapy requires treatment with a combination of long-acting agents. PMID- 2193710 TI - Our understanding of the Pasteurellaceae. AB - With the exception of a few consistent pathogens--Pasteurella multocida strains of bovine hemorrhagic septicemia and fowl cholera, Actinobacillus (Haemophilus) pleuropneumoniae, Haemophilus aegyptius and Haemophilus paragallinarum--members of the family Pasteurellaceae are commensal parasites on mucous membranes of vertebrate animals. Many have pathogenic potential, which becomes manifest under conditions of immunodeficiency and stress. Pathogenesis (except in porcine atrophic rhinitis) depends on mobilization of inflammatory responses probably in large part by endotoxin with contributions from protein toxins, which interfere with leukocyte activity and, by their cytotoxicity, cause exacerbation of the inflammatory reaction. Disease patterns include pneumonic/septicemic, upper respiratory and local/traumatic. Acquired resistance is chiefly antibody dependent, and, with current and emerging biotechnical resources, stands a good chance of being artificially achievable for many important diseases attributed to Pasteurellaceae. PMID- 2193711 TI - Public health training opportunities in Canada. PMID- 2193712 TI - Long-acting propranolol in the prophylaxis of migraine: a comparative study of two doses. AB - A randomized double-blind, cross-over study using treatment periods of 12 weeks with a 2-week washout, comparing two long-acting formulations of propranolol ('Inderal' LA 160 mg daily and Half-'Inderal' LA 80 mg daily) was performed after a placebo run-in of 4 weeks on 51 patients. The study indicated that both long acting formulations were significantly better than placebo in reducing the frequency of migraine attacks (p less than 0.01). After 12 weeks there was a significantly lower (p = 0.03) frequency of migraine attacks in patients on the higher dose formulation than in those on the lower dose formulation. There was no significant difference in the frequency of side effects produced by the two formulations. PMID- 2193713 TI - Flunarizine (10 and 20 mg) i.v. versus placebo in the treatment of acute migraine attacks: a multi-centre double-blind study. AB - In a multi-centre, randomized double-blind study, the effect and tolerance of 10 and 20 mg flunarizine i.v. versus placebo was tested on 102 migraineurs with acute migraine attacks with and/or without aura. Thirty-seven patients received 10 mg flunarizine, 32 received 20 mg and 33 received placebo. The groups were comparable. Response to treatment was defined as pain reduction of at least 50% within 60 min on a visual analogue scale after i.v. drug administration. This effect was noted on 59.4% with 20 mg flunarizine, on 24.3% with 10 mg flunarizine and on 30.3% with placebo. The tolerance of flunarizine i.v. was similar to placebo. Blood pressure and pulse rate were not affected by flunarizine. All in all, 20 mg flunarizine i.v. appeared to be a suitable alternative for treatment of acute migraine attacks. PMID- 2193714 TI - Cerebrovascular reactivity in migraineurs as measured by transcranial Doppler. AB - Transcranial Doppler ultrasound is a relatively new diagnostic modality which allows the noninvasive assessment of intracranial circulation. A total of 10 migraine patients were studied and compared to healthy controls without headaches. Migraineurs during the headache-free interval demonstrated excessive cerebrovascular reactivity to CO2, evidenced by an increase in middle cerebral artery blood flow velocity of 47% +/- 15% compared to 28% +/- 14% in controls (p = 0.026). Differences between the two study groups revealed no significant decrease in middle cerebral artery blood flow velocity with hypocapnia. However, the differences between middle cerebral artery blood flow velocity during hyperventilation and CO2 inhalation were significantly different (p = 0.004) comparing migraineurs and controls. Instability of the baseline blood flow velocities was also noted in migraineurs during the interictal period. Characteristics which may allow differentiation of migraineurs from other headache populations could possibly be obtained from transcranial Doppler ultrasound flow studies. PMID- 2193715 TI - Shigellosis: a killer disease. PMID- 2193716 TI - Platelet anti-aggregatory therapy in pregnancy: another role for low dose aspirin? PMID- 2193717 TI - Invasive haemo-dynamic monitoring: what do the numbers mean? PMID- 2193718 TI - Biotransformation and toxicity of inhalational anaesthetics. AB - In summary, anaesthetics and drugs used perioperatively are all xenobiotics and can be metabolized mainly by microsomal enzyme systems, which have a high activity in the liver. These enzyme systems are induced by repeated pre administration of drugs, such as barbiturates and others which are used during the preoperative period. However, according to some reports, aerobic and anaerobic metabolism is inhibited by the simultaneous administration of drugs, such as isoflurane and halothane, halothane and enflurane, and cimetidine and halothane. Hypoxia is also an important factor in hepatic disorders and it is well known that anaerobic metabolism of halothane is increased by hypoxia and its intermediate production produces a free radical. Theoretically, this free radical is involved in hepatic disorders. In practice, in order to prevent hepatic dysfunction before, during and after anaesthesia, hypoxia and repeated pre administration of enzyme-inducing drugs should be avoided. However, the choice and combination of drugs which inhibit drug metabolism and prevent hepato and/or nephro toxicity should be examined by further investigation. PMID- 2193719 TI - Respiratory monitoring of the infant in anaesthesia and intensive care. AB - Respiratory monitoring of children during general anaesthesia and critical care is in its early stages. Acquisition of physical information remains of great importance because of the difficulties in obtaining specific and objective data from paediatric patients. Many of the obstacles presented by them, such as small and rapid respiration, lack of patient cooperation, use of an uncuffed tracheal tube and relatively higher airway humidity to keep the small airway patent, have been overcome recently by sophisticated technology based on well known principles and thoughtful use of computers. It is now possible to monitor and apply many pulmonary function tests at the bedside that were once confined to the laboratory. PMID- 2193720 TI - Spinal headache--prevention and treatment. PMID- 2193721 TI - The appropriate use of inotropes in shock. PMID- 2193722 TI - Perioperative endocrine and electrolyte emergencies. PMID- 2193723 TI - Interpretation of non-invasive oxygen and carbon dioxide data. PMID- 2193725 TI - New drugs and new understandings of paediatric pharmacology. PMID- 2193727 TI - Another look at maternal inspired oxygen concentration during cesarian section. PMID- 2193726 TI - Anaesthesia for lung resection. AB - Management options to consider in the high-risk patient for pulmonary resection include: 1. The use of EAA plus a postoperative pain management scheme to optimize pulmonary function in the critical two to four days after surgery. 2. The use of a "step-down" or intermediate care area, with a level of monitoring between that of the intensive care unit and the regular postoperative ward, for the initial three to four days. 3. Preoperative optimization of concurrent medical conditions with aggressive physical and medical therapy. 4. Careful titration of intra-operative fluids with early recourse to invasive monitoring, vasopressors and inotropes. Perioperative digitalization of patients with a history of cardiovascular disease for pneumonectomy. 5. Avoidance of N2O. Ventilate intraoperatively with an air/oxygen mixture, during both two- and one lung ventilation, titrated against the arterial oxygen saturation. Avoidance of complete intraoperative atelectasis of the ND-lung with a low level of air/oxygen CPAP. 6. Surgical alternatives. The use of a median sternotomy or limited resection. A simple cost/benefit analysis tells us that not every recent advance in thoracic anaesthesia is indicated for every patient. It is now part of the anaesthetist's responsibility to identify the high-risk patient and to develop an appropriately stratified management plan. PMID- 2193724 TI - Changing practices in neuroanaesthesia. PMID- 2193728 TI - Alfentanil in minor surgery requiring tracheal intubation: a multicentre trial. PMID- 2193729 TI - A multicentre evaluation of alfentanil as an anaesthetic adjuvant in spontaneously breathing patients. PMID- 2193730 TI - Emergence respiratory complications in children: a comparison between halothane and isoflurane. PMID- 2193731 TI - Scalp infiltration with bupivacaine in paediatric brain surgery. PMID- 2193732 TI - Corticosteroids do not inhibit acute pulmonary response to fat embolism. PMID- 2193733 TI - Gastric emptying after clear fluids. PMID- 2193735 TI - DDAVP does not reduce bleeding during spinal fusion for idiopathic scoliosis. PMID- 2193734 TI - Supplemental oxygen during caesarean section under epidural anaesthesia: nasal prongs vs face mask. PMID- 2193736 TI - Atracurium and D-tubocurarine pretreatment in the prevention of succinylcholine myalgias: a study in vaginal hysterectomies. PMID- 2193737 TI - Propofol for induction and maintenance of anaesthesia: a comparison with thiopental-isoflurane. PMID- 2193738 TI - Intranasal nifedipine for post-bypass hypertension--hemodynamics and pharmacokinetics. PMID- 2193739 TI - The contribution of pharyngeal suction devices to sore throat after endotracheal anaesthesia. PMID- 2193740 TI - Continuous infusions of lumbar epidural fentanyl and intravenous fentanyl for post-thoracotomy pain relief. II: Respiratory effects. PMID- 2193741 TI - Acute cardiopulmonary effects of an anterior mediastinal mass. PMID- 2193742 TI - Bronchodilating effect of inhaled or orally administered calcium channel blocking agents on methacholine-induced bronchoconstriction. PMID- 2193743 TI - Effects of sevoflurane and halothane on pattern and mechanics of breathing in man. PMID- 2193744 TI - Alfentanil infusion for intra-abdominal surgery. PMID- 2193745 TI - A comparison of sedation for upper GI endoscopy using diazepam with demerol or midazolam with alfentanil. PMID- 2193746 TI - Catecholamine level and plasma renin activity during induced hypotension- adenosine vs sodium nitroprusside. PMID- 2193747 TI - Onset of subarachnoid bupivacaine in caesarean section. PMID- 2193748 TI - Axillary plexus block using a peripheral nerve stimulator: single or multiple injections. PMID- 2193749 TI - The clinical significance of diffusion hypoxia in children. PMID- 2193750 TI - The efficacy of indomethacin as a postoperative analgesic following total hip arthroplasty. PMID- 2193751 TI - Patient controlled lumbar epidural fentanyl for post thoracotomy pain. PMID- 2193752 TI - Epidural alfentanil during labor, in association with a continuous infusion of bupivacaine. PMID- 2193753 TI - Oxygen desaturation in elderly patients during cataract surgery. PMID- 2193754 TI - Intra-articular bupivacaine does not decrease narcotic requirements after arthroscopic surgery in adolescents. PMID- 2193755 TI - Analgesia and postoperative hypoxaemia after gastric partition with and without bupivacaine wound infiltration. PMID- 2193756 TI - Bupivacaine added to epidural fentanyl does not improve postoperative analgesia. PMID- 2193757 TI - Post spinal headache: a comparison of midline and laminar approaches. PMID- 2193758 TI - Continuous infusion epidural anesthesia for obstetrics. Bupivacaine vs bupivacaine-fentanyl. PMID- 2193759 TI - The effect of hyaluronidase on the speed of onset of retrobulbar anaesthesia. PMID- 2193760 TI - Topical liposomal tetracaine for i.v. cannulation. PMID- 2193761 TI - Continuous infusions of lumbar epidural fentanyl and intravenous fentanyl for post-thoracotomy pain relief. I: Analgesic and pharmacokinetic effects. PMID- 2193762 TI - Recovery after neuroleptanalgesia for cataract surgery. PMID- 2193763 TI - Balloon floatation is more important than flow-direction in positioning "flow directed" PA catheters. PMID- 2193764 TI - Fentanyl blunts the haemodynamic response of children to laryngoscopy. PMID- 2193765 TI - Transdermal scopolamine patches reduce postoperative emesis in pediatric patients undergoing strabismus surgery. PMID- 2193766 TI - Developmental expression of regionally specific cell surface antigens in the Xenopus gastrula. AB - Molecular markers for specific cell lineages would be useful in studies of cellular differentiation. To isolate such markers monoclonal antibodies (MoABs) were raised against plasma membranes isolated from gastrulating Xenopus embryos. Those antibodies that recognized subsets of cells within the embryo were selected by indirect immunofluorescence. The analysis of eight such MoAbs is presented. Western blot analysis showed that all but one MoAb recognized a complex pattern of glycoconjugates associated with glycoproteins. All the antigens recognized by the MoAbs were maternal in origin and displayed similar spatial patterns of pregastrular expression. This pattern of immunoreactivity at the apical surface was inherited passively during cleavage by the resulting superficial blastomeres suggesting that ectodermal specific markers of maternal origin are pre-localized to the cortical ooplasm in mature oocytes. We suggest that these maternal components may be specific glycosyl transferases. Three different patterns of expression were observed during gastrulation as exemplified by MoAbs 1F10C1, 3A4D1, and 6F10B6. MoAb 6F10B6 was specific for both neural and non-neural epithelium. MoAb 3A4D1 was specific for non-neural epidermis. MoAb 1F10C1 appeared to recognize a protein epitope on an extracellular component expressed by the superficial and involuting epithelial cells. The pattern of expression for the 1F10C1 antigen suggests that it may play a role in facilitating the movement of the involuting cells during gastrulation. PMID- 2193767 TI - Quartet: a Drosophila developmental mutation affecting chromosome separation in mitosis. AB - The Drosophila mutation, quartet, affects development at points in the life cycle that require intense mitotic activity. Examination of embryos affected by the maternal effect of quartet has revealed defects that can be attributed to incomplete chromosome separation at mitosis. These defects include uneven spacing of nuclei, strands of DNA creating bridges between nuclei, and abnormal amounts of DNA per nucleus. Nuclei in quartet-affected embryos also have a greater-than normal number of centrosomes. Immunofluorescent examination of the spindles in quartet-affected embryos has revealed tripolar spindles and adjacent spindles that share a common spindle pole. Finally, chromosome separation distance was measured in anaphase and telophase spindles in quartet-affected embryos and found to be blocked in anaphase. Examination of mitotic figures in quartet larvae revealed a reduced mitotic index and an elevated frequency of abnormal mitotic figures. quartet could encode a function necessary for the disengagement of chromosomes in mitosis, for kinetochore function or for function of a spindle motor. Mutations in quartet prevent the post-translational modification of three abundant proteins. These proteins may be involved in chromosome separation in mitosis. PMID- 2193768 TI - Musculoskeletal injuries caused by weight training. Guidelines for prevention. AB - Tens of thousands of U.S. children, adolescents, and young adults are using weights either recreationally, to train for sports, or to compete in weight lifting, power lifting, or body building contests. Weight use may cause significant musculoskeletal injury. This review summarizes for the clinician the best available information on injury risks and prevention. PMID- 2193769 TI - Spontaneous perforation of the extrahepatic biliary tree in infancy. A case report. AB - Spontaneous perforation of the bile duct in infancy is rare, with less than 55 cases described in the literature to date. The authors report the case of a 30 day-old neonate who presented with a 2-week history of progressive abdominal distension and intermittent jaundice. Disofenin technicium 99m sequential scintiscanning provided a preoperative noninvasive confirmation of the diagnosis of biliary ascites secondary to spontaneous perforation of the extrahepatic biliary tract. Distal common bile duct atresia was identified intraoperatively, and end-to-side Roux-en-Y hepaticojejunostomy was performed, with an uneventful postoperative recovery. The etiology, diagnosis, and treatment of spontaneous neonatal biliary perforation is discussed. PMID- 2193770 TI - Insulin secretion and sensitivity in acromegaly. AB - To examine the effect of excess growth hormones on carbohydrate metabolism, we studied glucose-stimulated insulin secretion and glucose utilization in 6 patients with acromegaly and 6 age-, sex- and weight-matched normal subjects. The levels of plasma glucose and serum insulin were determined during fasting and every 30 min up to 180 min after 75 g of oral glucose loading. In addition, plasma glucose, serum insulin and serum C-peptide were measured during euglycemic glucose clamp with insulin infusion of 40 mU/m2,min-1. The acromegalic patients had significantly higher mean levels of fasting plasma glucose (p less than 0.05) and insulin (p less than 0.01). After glucose loading for 3 h, the acromegalic patients also had a higher incremental area under the curve of plasma glucose (p less than 0.05) and serum insulin (p less than 0.05). However, no significant difference in the fasting molar ratio of C-peptide/IRI was noted between these two groups. During euglycemic clamp studies, the steady-state serum insulin levels were identical between the two groups. The glucose disposal rate was lower in acromegalics than in normal subjects (p less than 0.01). The results demonstrated that glucose intolerance, hyperinsulinemia and insulin resistance are present in acromegalic patients. PMID- 2193771 TI - Sensitivity of freshly isolated ovine adipocytes to inhibition of lipolysis by insulin. AB - 1. Ovine adipocytes were isolated in the presence of adenosine to minimize cell damage and were incubated at a low cell concentration. 2. Insulin sensitivity of lipid metabolism was retained. 3. Insulin inhibited basal lipolysis by 61% and isoproterenol- and adenosine deaminase-stimulated lipolysis by 84%. 4. Insulin increased glucose conversion to cell lipid by 3-fold. PMID- 2193772 TI - Transfection of cultured fish cells RBCF-1 with exogenous oncogene and their resistance to malignant transformation. AB - 1. Plasmids bearing the G418-resistant gene neo were transfected into cultured fish cells RBCF-1 by electroporation at an efficiency comparable to that in NIH3T3 cells. 2. Transfection of plasmids bearing both neo and activated human c Ha-ras into NIH3T3 and RBCF-1 cells resulted in the malignant transformation of the former but not of the latter cells. PMID- 2193773 TI - Safety of protamine sulfate administration in vasectomized men. AB - The majority of vasectomized men develop antibodies against different sperm antigens, including protamine. Due to the fact that salmon protamine is used clinically for heparin reversal and that a cross-reactivity has been observed between human and salmon protamine, vasectomized men may be at risk for adverse reactions to protamine sulfate. In order to explore this possibility, serum samples were analyzed for the presence of anti-sperm and anti-protamine antibodies in 20 vasectomized and 20 non-vasectomized men (controls) about to undergo major heart surgery requiring heparin reversal. The patients were closely monitored for any possible reaction following the injection of protamine. Anti sperm antibodies were detected in the serum of 15 of the vasectomized men whereas only two of the non-vasectomized subjects had this type of antibody. Twenty-five percent of the vasectomized men presented with anti-protamine antibodies; in the control group, none of the patients had developed this type of antibody. Following the administration of protamine sulfate, none of the patients in either group showed any adverse reaction to the drug. It is concluded that vasectomized men are not at increased risk towards adverse reactions following the injection of protamine sulfate. PMID- 2193775 TI - Pulmonary edema in falciparum malaria. Slaying the dragon of volume overload. PMID- 2193774 TI - Randomized trial of the effect of drugs on cervical dilatation for termination of first trimester pregnancy. AB - A randomized triple-blind and placebo-controlled clinical trial on the effect of lidocaine and Anodyne-lubricant jelly (ALJ) containing dicaine on cervical dilatation is reported. Three-hundred-seventy-two consecutive cases were randomly allocated to 4 groups. The four groups were given: ALJ and placebo (placebo 1); and lidocaine and placebo (placebo 2). ALJ and placebo 1 treatment was by topical application, and lidocaine and placebo 2 by injection. In parous women, a significant difference was found for satisfactory dilatation (SD) rate (p less than 0.01) among four groups. It was unexpected that there were no significant differences between drug and placebo groups, neither between ALJ treatment group and placebo 1 group (p greater than 0.5), nor between lidocaine and placebo 2 (p greater than 0.75). However, the combined SD rate was 60.9% for the topical groups compared with 39.0% for the injection groups (p less than 0.005). The findings suggested that the effect of ALJ on cervical dilatation was not mainly due to dicaine, but associated with the lubricant and the topical treatment. PMID- 2193776 TI - Ultrasound guidance improves the success rate of internal jugular vein cannulation. A prospective, randomized trial. AB - STUDY OBJECTIVE: To compare conventional versus ultrasound-guided internal jugular vein cannulation techniques. DESIGN: Patients were randomly assigned to receive either conventional or two-dimensional ultrasound-guided internal jugular vein cannulation. Patients who could not be cannulated with five or fewer passes by either technique, were crossed over to the other technique. SETTING: Clinical research unit in a tertiary care center. PATIENTS: All consecutive patients who required urgent or urgent-elective internal jugular vein cannulation during the study period. INTERVENTIONS: The two-dimensional ultrasound transducer imaged all cannulation attempts. For patients randomized to ultrasound guidance, the operator viewed two-dimensional ultrasound images, and received verbal guidance from the ultrasound technician. For patients randomized to the conventional arm, two-dimensional ultrasound images were recorded without visual or verbal feedback. MEASUREMENTS AND MAIN RESULTS: Two-dimensional ultrasound was significantly better than conventional guidance in reducing the number of failed site cannulations from 6/17 (35 percent), to 0/12 (0 percent), p less than 0.05. Two-dimensional ultrasound also reduced the mean number of passes required to cannulate the vein from 3.12 to 1.75 (p less than .05), and was also successful in six/six (100) of patients who failed cannulation by conventional means (p less than 0.05). CONCLUSIONS: Intensivists can increase successful internal jugular vein cannulation using ultrasound guidance. Two-dimensional ultrasound should be considered for patients difficult to cannulate or those at high risk of cannulation complications. PMID- 2193777 TI - Intensive management of severe head injury. AB - Intensive management of patients with severe head injury offers the best hope of minimizing death and functional disability in a young, working population. Secondary neurologic insult can be decreased by cardiorespiratory support and ICP control from the outset. Rapid neurologic assessment, airway management, and support of circulation are the basis of emergency management for head injury. Patients with severe head injury require intensive care management for two major reasons: management of ICP and management of organ system dysfunction. Care should not be withheld because of initially grim (and inaccurate) prognostic assessment. Newer techniques for assessing the adequacy of cerebral circulation may allow refinement of management strategies in the future. PMID- 2193778 TI - Viral heart disease. PMID- 2193779 TI - Valve site-specific pathogenetic differences between right-sided and left-sided bacterial endocarditis. PMID- 2193780 TI - Utility of animal models in the study of human airway disease. PMID- 2193781 TI - Circadian influence in cardiovascular disease (Part 2). PMID- 2193782 TI - Exudative polyserositis and acute respiratory failure following praziquantel therapy. AB - Praziquantel is recommended as the drug of choice for all forms of schistosomiasis. We report the first case (to our knowledge) of exudative effusive polyserositis following treatment of schistosomiasis with this drug. This involved pleura, pericardium, and peritoneum and was associated with acute respiratory failure. The latter preceded the appearance of pleural effusions. We present a brief review of the literature and attract attention to the need for close observation of patients with schistosomiasis who are treated with praziquantel. PMID- 2193783 TI - Management of asthma and chronic airflow limitation. Are methylxanthines obsolete? AB - After almost 50 years as first-line drugs in the management of asthma and COPD, methylxanthines have been largely superceded by inhaled adrenoceptor agonist and anticholinergic bronchodilators which are more potent and far less toxic. Accumulating evidence indicates that intravenous theophylline contributes side effects, but is rarely of benefit in acute exacerbations of asthma or COPD. In the maintenance therapy of asthma, first-line therapy is dose-optimized inhaled steroids, reducing the need for bronchodilators. Inhaled adrenoceptor agonists are second line medications, anticholinergic aerosols third line, and theophylline, if needed at all, may fulfill a minor systemic steroid-sparing function in severe asthmatics on maximum doses of the inhaled medications. In the maintenance therapy of some patients with COPD, theophylline sometimes may be useful but these responders should be identified by objectively establishing therapeutic benefit. Since many patients have side effects from the methylxanthines, while their therapeutic benefit over and above dose-optimized inhaled therapy is marginal, their continued almost routine use in the management of reversible airflow obstruction is hard to justify, although this class of drugs may be useful in selected patients in whom both subjective and objective benefit can be demonstrated. In COPD, theophylline may improve exercise capacity in some patients by still incompletely understood mechanisms probably unrelated to bronchodilation. PMID- 2193784 TI - Delorme's transrectal excision for internal rectal prolapse. Patient selection, technique, and three-year follow-up. AB - Surgical therapy of functional outlet obstruction in patients with internal rectal intussusception may include abdominal, perineal, or transrectal procedures. Because abdominal procedures often result in significant physiologic impact but unrelieved constipation, the authors have elected Delorme's transrectal excision for management of these patients. Since a short-term "placebo" effect attends many therapies, this report describes results of transrectal excision only after a three-year postoperative period. Delorme's transrectal excision of internal intussusception accomplished sustained symptomatic relief in over 70 percent of otherwise refractory constipated patients. The association of internal intussusception with other abnormalities underscores the importance of defining both anatomic and functional components when selecting patients whose constipation may require surgical therapy. Critical technical elements, surgical pitfalls, and potential complications of the procedure are discussed. PMID- 2193785 TI - Malignant lymphoma in ulcerative colitis. Report of a case. AB - The authors present the case of a 40-year-old woman with primary malignant lymphoma complicating chronic ulcerative colitis. Twenty-one cases reported in the literature are reviewed and the various available data analyzed. Variations in the distribution of lymphoma in both the normal and colitic bowel supports a relationship between both conditions. Any lymphocytic infiltrate seen in biopsies obtained from ulcerative colitis should be assessed to exclude associated lymphoma. The prognosis is poor. PMID- 2193786 TI - Hirschsprung's disease in adolescents and adults. AB - Hirschsprung's disease in the adolescent and adult is a rare and often misdiagnosed cause of lifelong refractory constipation. Two adolescent and three adult patients with Hirschsprung's disease treated between 1973 and 1987 at the University of Michigan Medical Center are reported. Each patient presented with chronic constipation requiring enemas, cathartics, and multiple hospital admissions for management. Diagnosis in each case was made with barium enema and full-thickness rectal biopsy. Four patients underwent endorectal pull-through procedures, all with good long-term results. The fifth patient, initially treated with a Duhamel retrorectal pull-through procedure, required reoperation for constipation secondary to a retained rectal septum. Review of 199 cases of adult Hirschsprung's disease enables comparison of the various operative procedures for this disorder with respect to postoperative complications and functional outcomes. Anorectal myectomy with low anterior resection, the Duhamel-Martin procedure, and the Soave endorectal pull-through procedure are the most acceptable methods for surgical management. PMID- 2193787 TI - [Sex-specific changes in body composition during weight reduction]. AB - The aim of this study was to ascertain whether overweight men and women of comparable age, body surface area and weight would display any differences in weight loss or changes in body composition while receiving identical calorie intakes. 15 men and 15 women of mean age 46.7 (26-57) years with obesity (body mass index 29-36 kg/m2) were given a reducing diet containing 700 kcal/d for 4 weeks. The two groups were identical in age, body weight and height. The change in body composition was studied by means of ultrasound and nitrogen balance. The women had thicker layers of subcutaneous fat (241 +/- 8 mm) over all parts of the body than the men (137 +/- 10 mm) (summated measurements at 14 points). Among the men body weight fell from 93.1 +/- 2.1 to 83.8 +/- 2.0 kg, but the women declined only from 92.9 +/- 2.0 to 84.7 +/- 1.9 kg. Although men achieved a greater weight loss (13%; P less than 0.001) the decrease in their subcutaneous fat layer was 33% less (to 117 +/- 9 mm) than in the women (211 +/- 8 mm). Cumulative nitrogen balance among the men was 4.7 times more negative than in women (-104 +/- 14 g versus -22 +/- 11 g); this points to accentuated muscle breakdown. More fat was mobilized in the women than in the men, chiefly from the regions of the limbs and hips. PMID- 2193788 TI - [The mitochondrial genome and its deletions as a cause of disease]. PMID- 2193789 TI - [Vasculitis. The differential diagnostic value of biopsy]. PMID- 2193790 TI - [Fibrinolysis therapy using APSAC in acute myocardial infarct]. PMID- 2193791 TI - [Compression sonography as a screening method in thrombosis diagnosis]. AB - The incidence of thromboses in the leg was studied in 542 patients (220 women and 322 men, mean age 61 [15-88] years) in a medical intensive care unit who had routinely undergone ultrasound examinations of the venous system of the legs. Not previously known thromboses were demonstrated in 62 (11.4%) of patients, bilaterally in 27.4% of them. Thromboses were most frequent (28.8%) in patients with malignant disease, rarest (3.7%) in those with myocardial infarction. 45% of thromboses were located solely in the lower leg. Autopsy, performed in 87 of the patients, revealed recent pulmonary emboli in 14. In eight of them venous thrombosis had been diagnosed by ultrasound before death, while the total number of leg vein thromboses identified in the 87 patients was 11. PMID- 2193793 TI - [The diagnosis in facial pains]. PMID- 2193792 TI - [Systemic fibrinolysis following resuscitation or temporary electrostimulation]. AB - Short-term systemic thrombolytic treatment with 1.5 million I.U. streptokinase or 1.8 million I.U. urokinase or APSAC was carried out in 13 patients with acute myocardial infarction (11 men, 2 women, mean age 61 [44-73] years) after cardiopulmonary resuscitation (n = 11) or transvenous electrostimulation (n = 2). In seven of the patients the infarct vessel was found to be patent after the course of thrombolytic therapy. No haemorrhagic complications occurred. Two patients died: one of a reinfarct at 3 months and the other suddenly at home at 6 months. These results show that short-term high dosage systemic thrombolytic treatment can be successfully performed in individual cases even after resuscitation or central venous catheterization, provided that any serious traumatic lesions or inadvertent arterial punctures have been avoided. PMID- 2193794 TI - Modulation of adrenal chromaffin cell intracellular calcium by angiotensin, bradykinin and endothelin. AB - Studies were undertaken to compare and contrast the effects of the vasoactive peptides, angiotensins II and III, bradykinin and endothelin, on mobilization of intracellular calcium in isolated, cultured bovine adrenal medullary (chromaffin) cells. Calcium mobilization was studied using the Fura-2 technique. The potency for elevating intracellular calcium, compared on a molar basis, was bradykinin greater than angiotensin III greater than angiotensin II much greater than endothelin. When nicotine and angiotensin II were added together, a synergism was evident with prolonged elevation of intracellular calcium. However, concomitant addition of angiotensin II and endothelin was barely additive. Yet, combined addition of endothelin and depolarizing potassium chloride yielded a very marked synergism in calcium mobilization. We conclude that the multiplicity of vasoactive peptide receptors on chromaffin cells exert interactive modulation on calcium mobilization in these cells and this property may have functional significance. PMID- 2193795 TI - Circulating neuroactive peptides and the blood-brain and blood-cerebrospinal fluid barriers. AB - Interactions of radiolabelled circulating neuroactive peptides: enkephalin leucine (Enk-Leu), delta sleep inducing peptide (DSIP), thyrotropin-releasing hormone (TRH) and vasopressin-arginine (VP-Arg) with the blood-brain and blood cerebrospinal fluid barriers were studied by mean of: 1. a vascular perfusion technique in the guinea-pig using multiple-time brain uptake analysis, 2. a vascular perfusion technique of the in situ isolated choroid plexus from sheep using single-circulation paired-tracer dilution or steady-state analysis. It has been demonstrated that Enk-Leu, DSIP and VP-Arg were taken up intact at the luminal side of the blood-brain barrier and blood-tissue interface of the blood cerebrospinal fluid barrier by a saturable mechanism. On the other hand, a non saturable mechanism as well as possible enzymatic degradation were shown during TRH interactions with either the blood-brain or blood-cerebrospinal fluid barriers. It is concluded that both, facilitated and simple diffusion, govern circulating neuroactive peptide uptake into the central nervous system. PMID- 2193796 TI - Cell-type specific posttranslational processing of peptides by different pituitary cell lines. AB - In order to compare prohormone processing in two distinct pituitary cell types, somatomammotrope cells (GH3) and corticotrope cells (AtT-20) were stably transfected with vectors encoding preproneuropeptide Y (preproNPY) containing four different pairs of basic amino acids at the single endoproteolytic cleavage site: wildtype or KR (lysine-arginine), RR, RK, and KK. The GH-NPY cell lines cleaved proNPY to a similar extent, regardless of the sequence of the basic amino acids at the cleavage site (KR = RR = RK = KK). AtT-20-NPY cells are known to exhibit a strong hierarchy of cleavage site preference when processing wildtype and mutated proNPY forms (KR = RR greater than RK much greater than KK). All four types of GH-NPY and AtT-NPY cells faithfully produced NPY (1-36) NH2 from proNPY (1-69), regardless of the amino acid sequence at the cleavage site. All four types of GH-NPY cells produced some of the expected proNPY-COOH-terminal peptide with Ser40 at its NH2-terminal [proNPY (40-69)]. GH3 cells expressing the RR, RK, and KK forms of proNPY yielded in addition some proNPY-COOH-terminal peptide retaining the amino terminals Lys39 or Arg39 residue. In contrast, AtT-NPY-RK cells produced only the Lys39 form of proNPY-COOH-terminal peptide while the other three AtT-NPY lines (KR, RR, and KK) produced only the Ser40 form of proNPY COOH-terminal peptide. The residence time of proNPY and NPY in GH3 cells was dramatically increased by treatment with insulin, estradiol, and epidermal growth factor, in concert with the expected increase in PRL synthesis and decrease in GH synthesis; increased residence time in the cells did not result in an increase in the extent of cleavage of proNPY to NPY. AtT-20 cells did not respond to the somatomammotrope-specific set of hormones. Thus, there are several important differences in the posttranslational processing and storage of peptide hormones in corticotropes and somatomammotropes. PMID- 2193797 TI - Immunohistochemical demonstration of a novel hypothalamic peptide, pituitary adenylate cyclase-activating polypeptide, in the ovine hypothalamus. AB - We recently reported isolation, characterization and synthesis of a novel ovine hypothalamic peptide with 38 residues which stimulates accumulation of cAMP in rat anterior pituitary cell cultures. The peptide was named PACAP38 (pituitary adenylate cyclase-activating polypeptide with 38 residues). The presence of another peptide corresponding to the N-terminal 1-27 residues (PACAP27) was also demonstrated. Both PACAP38 and PACAP27 have an amidated C-terminus. Antisera against synthetic PACAP27 were generated in rabbits. These antisera were tested for titer and specificity in enzyme-linked immunosorbent assay. One of the antisera (no. 88121-3) exhibited a high titer of antibody, which was specific to PACAP27 and PACAP38 with exception of slight cross-reactivity with ovine CRF (oCRF). Therefore, the antibodies against oCRF were removed from the antiserum using a solid phase method. Removal of oCRF antibodies was confirmed by enzyme linked immunosorbent assay. A dense immunoreactive fiber network was found in both external and internal zones of the median eminence and pituitary stalk. The fibers were demonstrated to be in close contact with the hypophysial portal capillaries. The preabsorption of antiserum with vasoactive intestinal polypeptide or with the mixture containing TRH, LHRH, oCRF, ovine GH-releasing factor, somatostatin, and bovine thyroglobulin did not affect the immunostaining. On the other hand, the preabsorption of antiserum with an excess of PACAP27 or PACAP38 abolished the immunostaining. Therefore, the staining is considered specific for PACAP27 and PACAP38. Stained fibers were also present in the posterior pituitary. A dense fiber network was observed and the lateral hypothalamus the fibers appeared to cling to unstained neuronal cell bodies and their dendrites. In the lateral septum the fibers surrounded some blood vessels. Immunolabeled cell bodies were found in the paraventricular and supraoptic nuclei. These findings support the view that PACAP may play a multifunctional role, including that of a hypophysiotropic hormone, neurotransmitter, neuromodulator, and vasoregulator. PMID- 2193798 TI - In vivo and in vitro modulation of gonadotropin-releasing hormone metabolism by estradiol and progesterone. AB - The metabolism of GnRH by membrane-bound and serum-degrading enzymes may play an important role in the regulation of pituitary gonadotropin secretion. We examined GnRH metabolism by pituitary cells in vitro and the metabolism of exogenously administered GnRH in vivo in the presence and absence of estradiol (E2) and progesterone (P4). Ovariectomized cynomolgus monkeys were implanted with E2- and/or P4-filled Silastic capsules to simulate the estrogen and progesterone patterns of the normal menstrual cycle. Peripheral levels of GnRH after a 1 microgram iv injection were highest in the E2-replaced monkeys. Peripheral GnRH levels reached a higher peak and remained in circulation longer in monkeys treated with E2-filled Silastic implants than in those treated with E2 plus P4 or nonsteroid-replaced ovariectomized monkeys. In agreement with the in vivo data, GnRH was rapidly metabolized by acutely dispersed cells isolated from pituitaries removed from nonsteroid-replaced ovariectomized monkeys. Priming with E2 followed by P4 in vivo attenuated the clearance of GnRH in vitro, and E2 treatment alone almost completely blocked the ability of pituitary cells to bind and/or degrade GnRH in vitro. In a parallel study, cells prepared from rat pituitaries removed on the morning of proestrus (when serum E2 is highest) metabolized GnRH in vitro more slowly than pituitary cells removed at estrus, diestrus, or metestrus. In summary, our data suggest that E2 inhibits GnRH metabolism by monkey and rat pituitary cells in vitro and exogenously administered GnRH in vivo. Although the precise mechanism of action of E2 is unknown, inhibition of membrane-bound and serum proteases seems likely. The action of E2 may be to increase GnRH presentation to the pituitary and enhance LH and FSH secretion under conditions where circulating levels of the hormone are elevated, such as at midcycle. PMID- 2193800 TI - Household coping strategies and contradictions in response to seasonal food shortage. AB - Uncertainty is a primary consideration in adjusting to seasonal environments as attempts are made to synchronize productive inputs with critical periods in the annual cycle. Coping responses of small scale producers therefore rely on the coordination and control of diverse resources, and on flexibility in choosing between multiple options. Generalizations concerning seasonal coping responses to food shortage of households, and of women within households, are reviewed. Particular attention is given to how socio-economic differentiation affects the capacity to use such strategies, and how these differ with regard to the degree of resource commitment and reversibility once initiated. Our primary concern is in exploring the process whereby seasonal strategies become eroded. Thus, as seasonal uncertainties are exacerbated by unpredictable fluctuations in commercial economies, and as productive resources become less accessible to households, adaptive conflicts and contradictions are introduced. Uncertainty is further intensified by illness and unequal access to adaptive options based on class and gender. The increasing inability of small scale producers to cope with seasonal uncertainty emphasizes the need to understand this erosive process. PMID- 2193799 TI - The effect of protein kinase-C inhibition on insulin receptor phosphorylation. AB - The effect of protein kinase-C (PKC) inhibition on insulin receptor phosphorylation in HepG2 cells was analyzed by two-dimensional tryptic phosphopeptide maps. In basal cells, there was one major insulin receptor-derived tryptic phosphothreonine peptide and at least four phosphoserine peptides. Phorbol 12,13-dibutyrate (PDBU) stimulated phosphorylation of the phosphothreonine peptide, some of the basal phosphoserine peptides, and at least one phosphoserine peptide that was not detected in the basal state. Staurosporine completely inhibited the PDBU-mediated phosphorylation. Although staurosporine also inhibited basal phosphorylation of the phosphothreonine peptide, down regulation of PKC did not, suggesting that PKC does not mediate basal insulin receptor phosphorylation. Insulin treatment resulted in the appearance of four phosphotyrosine peptides. It also stimulated the phosphorylation of at least two phosphoserine peptides. One of these may have been a complex of two or more distinct but poorly resolved phosphopeptides, which was seen in basal cells and a component of which seemed to be stimulated by PDBU. However, neither staurosporine nor down-regulation of PKC diminished insulin-stimulated serine phosphorylation of these peptides, indicating that insulin-stimulated receptor serine phosphorylation did not involve PKC activity. The addition of staurosporine to cells that had been incubated with PDBU resulted in the very rapid decay of phosphorylation of the phosphothreonine-containing peptide, indicating that this site of phosphorylation turns over very rapidly, while some of the other phosphoserine-containing peptides, including the major unique site of phosphorylation stimulated by PDBU, turned over more slowly. Thus, the insulin receptor contains several sites of serine/threonine phosphorylation, some of which are substrates for more than one protein kinase. This may permit complex modulation of insulin receptor functions in response to multiple signalling pathways. PMID- 2193801 TI - The integrated analysis of seasonal energy deficits: problems and prospects. AB - The emergence of energy flow studies is reviewed, from their origins in ecosystem research in the 1950s, to their application to agricultural systems suffering from the 'energy crisis' of the 1970s, and the application of Optimal Foraging Theory to small-scale societies. Methodological problems are then discussed, in particular problems of measuring human and draft animal labour, ways of assessing fuel energy and the contribution of biomass to cultivation, and the need to define appropriate spatial and temporal units for analysis. Finally, the scope for studying seasonal energy deficits by means of an integrated analysis of energy flows is considered. The household unit is identified as the most promising unit for such analysis. PMID- 2193802 TI - Seasonal energy stress in marginally nourished rural women: interpretation and integrated conclusions of a multicentre study in three developing countries. PMID- 2193803 TI - Role of the sympathetic nervous system in adaptation to seasonal energy deficiency. AB - The sympatho-adrenal system is involved in the regulation of energy metabolism and responds to changes in energy intake. Energy restriction diminishes the sympathetic drive while overfeeding increases it. Chronically energy deficient subjects show an enhanced alpha and beta receptor responsiveness, which may be of a denervation type, associated with the reduced sympathetic activity that results from the decrease in dietary energy intake. The reduced basal metabolism of energy restricted subjects is partly attributable to the decrease in sympathetic activity. Chronically energy deficient individuals also show a suppressed thermogenic response to infusions of adrenergic agonists such as noradrenaline. Although sympathetic activity plays a modulating role in the energy homeostasis of the chronically energy deficient, it is not possible to explain seasonal fluctuations in energy balance. PMID- 2193804 TI - The possible role of skeletal muscle in the adaptation to periods of energy deficiency. AB - Skeletal muscle accounts for a large portion of the body's energy expenditure both at rest and during exercise. The present review focuses on some possible mechanisms for economizing energy in resting and contracting skeletal muscles, and on the available information about whether these mechanisms are important in the energy-deficient body. There is evidence, both in man and in the rat, that in a state of energy deficiency the size of slow-twitch fibres is better preserved than that of the fast-twitch fibres. Slow-twitch fibres have a lower activation threshold, and this seems to decrease their responsiveness to starvation. This would be advantageous as there is evidence that the energy expenditure per unit tension developed is lowest in slow-twitch fibres. There are reports of a slowing of malnourished muscle, but it is uncertain whether the starvation-induced hypothyroid state leads to some degree of fast-to-slow fibre transformation. Muscle glucose oxidation is depressed by starvation, mainly due to changes outside the muscle itself, but muscle enzymatic adaptations may also be important in this energy-saving process. In this respect, the higher capacity of the fatty acid oxidation and aerobic end-oxidation pathways in slow-twitch fibres tend to make them better adapted than fast-twitch fibres. Further muscle adaptations might include a decrease in BMR, possibly by reductions in protein turnover, ion pumping or futile cycling. The importance and costs of such potential adaptations should be evaluated by further research. This knowledge will be an important step in the further understanding of the pathophysiology of starvation. PMID- 2193805 TI - The mechanisms for minimizing energy expenditure in human locomotion. AB - In walking and in running the progression of the body involves at each step changes in kinetic energy, Ek, due to acceleration and deceleration, and changes of potential energy, Ep, due to vertical displacement. The energy costs of walking and running are minimized by two different mechanisms. In walking an alternate exchange of Ek and Ep takes place at each step, so that the muscles have only to restore the small part of the energy that is not recovered. The most economical speed of walking is that at which this recovery is maximal. In addition, at each speed there is an optimal frequency at which the total (external plus internal) mechanical power, and hence the metabolic cost, is minimal. In running the changes of Ek and Ep are almost completely in phase, implying a greater energy dissipation than in walking: part of this energy is stored by stretching the elastic elements of the previously contracted muscles and recovered during the following cycle, increasing the overall efficiency of the progression. The energy cost of walking with a load increases proportionally with the load. However, walking at low speed with a load not exceeding 5-10 per cent of the body weight is not more expensive than unloaded walking. Moreover, it has been observed that African women walking at their optimal speed can carry on their heads loads of up to 20 per cent of their body weight without any extra cost. A possible explanation of this finding could be that a different distribution of the body mass, with a higher position of the centre of gravity of the body, further increases the recovery of energy at each step. PMID- 2193806 TI - Seasonal fluctuation of BMR in populations not exposed to limitations in food availability: reality or illusion? AB - Re-analysis of literature data has revealed that BMR seasonal fluctuations largely depend on indoor and outdoor temperatures at the time of determination. BMR seasonal differences persist even after controlling for indoor temperatures, suggesting the existence of other factors controlling modifications of BMR in the normal population throughout the year. PMID- 2193807 TI - Prolonged luteal activity in mares--a semantic quagmire. AB - Prolonged luteal activity is one of the most formidable terminology challenges in mare reproductive biology. Prolonged luteal activity can be a result of persistence of an individual corpus luteum or the sequential development of luteal glands, each of which may have a normal life span. Luteal tissue can originate from an unovulated follicle or from an ovulation occurring during either follicular or luteal dominance. These complexities, together with ambiguous and inconsistent terminology, have resulted in confusion regarding those conditions which can be grouped broadly under the term prolonged luteal activity. Persistence of an individual corpus luteum can occur in association with severe damage to the endometrium resulting in loss of the uterine luteolytic mechanism. Spontaneous (no known uterine pathology) persistence of the corpus luteum from the follicular-phase ovulation has not been documented adequately as a clinical entity. The occurrence of ovulation towards the end of dioestrus may cause confusion about the origin of prolonged luteal activity. Such immature dioestrous corpora lutea may not respond to the release of uterine luteolysin, thereby leading to prolonged luteal activity even though the original corpus luteum regressed at the normal time. In the absence of critical monitoring of the corpus luteum (eg by ultrasound) the prolonged activity could be attributed erroneously to persistence of the corpus luteum from the follicular-phase ovulation. Pseudopregnancy is another confusing term that is sometimes used to describe persistence of the corpus luteum, especially when the luteal persistence is caused by embryonic loss after the embryo has blocked the uterine luteolytic mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2193808 TI - Haemodynamic effects of ACE inhibitors. AB - This paper reviews the haemodynamic effects of angiotensin-converting enzyme (ACE) inhibitors in hypertension, focusing on their ability to cause a fall in systemic vascular resistance, with no change in cardiac output and no reduction and even an increase in blood flow to vital organs such as the brain, the kidney and the heart. The haemodynamic effects of ACE inhibitors are qualitatively similar in congestive heart failure, except that, in the presence of impaired cardiac function, the fall in resistance is accompanied by a pronounced increase in cardiac output and tissue perfusion. In both conditions ACE inhibition opposes sympathetic influences and enhances vagal influences and, in hypertension, this intervention is followed by a regression of left ventricular hypertrophy providing a multifold background for a cardioprotective action. The new ACE inhibitor quinapril appears to share the haemodynamic effects of other ACE inhibitors with an improvement of cardiovascular function in congestive heart failure. PMID- 2193809 TI - ACE inhibitors in the treatment of hypertension in the older patient. AB - Hypertension is a major potential problem among the increasing number of older persons in the population, threatening their health and shortening their life expectancy due particularly to stroke and congestive heart failure (CHF). Controlled studies have shown that antihypertensive drug therapy reduces the incidence of severe CHF, stroke and cardiovascular mortality in the elderly. Special consideration should be given to altered drug metabolism, altered responses to drugs, and concomitant medications when pharmacotherapy is instituted in the elderly. Angiotensin-converting enzyme (ACE) inhibitors are acceptable in the hypertensive older patient as first-line therapy for all grades of hypertension and as second-line therapy for the patient with CHF. Use of ACE inhibitors avoids many of the symptoms and metabolic disturbances associated with beta-blockers and diuretics. Quinapril is a new non-sulphydryl ACE inhibitor whose active metabolite, quinaprilat, has a relatively short accumulation half life compared with enalapril and lisinopril but has an enhanced affinity for the converting enzyme, allowing rapid excretion of the drug while retaining a 24-hour antihypertensive effect with once-daily dosing. Quinapril is a valuable addition to the ACE inhibitor class, with demonstrated efficacy and safety in the older patient. PMID- 2193810 TI - Why do the kidneys release renin in patients with congestive heart failure? A nephrocentric view of converting-enzyme inhibition. PMID- 2193811 TI - ACE inhibitors in mild heart failure: first-line or second-line therapy? AB - Despite the successful therapeutic applications of angiotensin-converting enzyme (ACE) inhibitors to date, knowledge of how they work and guidelines for their use are still incomplete. On their role as monotherapy in congestive heart failure, we have scarce and conflicting data. Nor is there a clear answer to the question, when should an ACE inhibitor be started in a patient with heart failure? In patients with severe heart failure, the addition of an ACE inhibitor to a diuretic regimen has been shown to improve prognosis. In patients with mild heart failure, a benefit has not been demonstrated. In one preliminary report, monotherapy with the ACE inhibitor quinapril was shown to improve exercise time and functional class in patients with mild heart failure compared to placebo. PMID- 2193812 TI - [The history of the "deutsche maus", the origin of the dd mouse group]. AB - An inbred strain of mice, DDD, was established at the Institute for Infectious Diseases (so-called Denken in Japanese; currently called Institute of Medical Science, The University of Tokyo: Jms) in 1962. Many interesting characteristics including development of pregnancy-dependent mammary tumors, presence of Fv-2s, a Friend leukemia virus-susceptible gene, high incidence of hydronephrosis and low level of natural killer (NK) cell activity have been reported in this strain of mice. Two congenic strains, DDD-Fv-2r and DDD-Mtv-2+, have been produced. Inbreeding of dd mice maintained at Denken was commenced in 1957 and the resulting inbred strain was named DDD after dd at Denken. The ancestors of dd mice had come from Germany. The process of introduction to Japan and the history of these mice were surveyed in the literatures, since the description concerning them had been confused. As a result, the following history was confirmed: the original colony of mice of an unknown size was introduced from the Hoechst Company, Frankfurt a.m. Main, Germany into the Kitasato Institute, Tokyo, Japan by Dr. Tsuneo Komatsu under the direction of Dr. Sahachiro Hata in autumn, 1928. Dr. Hata and his colleagues bred these mice to use for medical researches and called them "deutsche Maus". Their descendants (one male and one female) were shipped to the Health Institute of Manchuria Railway, Talien (currently called Dalian), China on demand of Dr. Koji Ando in 1934. Two males and eight females from the Talien colony were shipped back to Dr. Saburo Kojima, the Institute for Infectious Diseases, Tokyo, Japan in 1943. They had been maintained without crossing with another colony at the Institute, from which mice were distributed to many institutes throughout Japan between 1944 and 1960, and served as the starting nuclei of many inbred or outbred strains. The "deutsche Maus" was named dd mice after "deutsche Maus at Denken" in 1952. Thus, the mouse strains connected with dd mice usually have D, DD or dd at the head in their names. PMID- 2193813 TI - [Development and age-related change of immune function in nonhuman primates]. PMID- 2193814 TI - [Longevity and memory]. PMID- 2193815 TI - [Composition of milk and electrophoretic analysis of milk casein in herbivorous voles (Microtus montebelli)]. AB - Milk samples were collected from herbivorous voles (Microtus montebelli) and their compositions were analyzed. Total solids, fat, protein and ash concentrations of vole's milk were very higher than those of cow's milk. The lactose concentration was very lower than that of milk of cow or mouse. The electrophoretic patterns of milk casein of vole were different markedly from those of bovine, but resembled to those of mouse. PMID- 2193816 TI - [Diagnosis of abortion and fetal death by the ultrasonographical device in cynomolgus monkeys under indoor individually-caged conditions]. AB - This paper describes the rate of naturally occurring abortion and fetal death that were diagnosed by the use of an ultrasonographical device in 683 pregnant cynomolgus monkeys (Macaca fascicularis) of which 542 were wild-imported monkeys and 141 were colony-bred monkeys. All of these animals had become pregnant by the 3-day timed mating system. The combined rate of abortion and fetal death was 7.0% in the wild-imported animals and 7.8% in the colony-bred animals. There were no significant differences in the rate with respect to different ages and to different period of feeding at Tsukuba Primate Center. Seventy-eight per cent (38 monkeys) of the total cases occurred during the first 5 to 9 pregnancy-weeks. PMID- 2193817 TI - Assembly of lipids into membranes. Introduction. PMID- 2193818 TI - Interaction of lipid transfer protein with plasma lipoproteins and cell membranes. AB - The hydrophobic lipid components of lipoproteins, cholesteryl ester and triglyceride, are transferred between all lipoproteins by a specific plasma glycoprotein, termed lipid transfer protein (LTP). LTP facilitates lipid transfer by an exchange process in which cholesteryl ester and triglyceride compete for transfer. Thus, LTP promotes remodeling of the lipoprotein structure, and plays an important role in the intravascular metabolism of these particles and in the lipoprotein-dependent pathways of cholesterol clearance from cells. The properties of LTP, its mechanisms of action, its roles in lipoprotein metabolism, and its modes of regulation are reviewed along with recent data that suggest a possible role for this protein in directly modifying cellular lipid composition. PMID- 2193819 TI - The assembly of lipids into lipoproteins during secretion. AB - The process of assembly and secretion of lipoproteins is discussed with particular reference to the role of lipids. The majority of circulating lipoproteins is produced by the liver (80%) with the remainder being supplied by the intestine. The liver secretes both very low density lipoproteins and high density lipoproteins, but the assembly and secretion of these two types of particles may follow different routes. The major lipid components of lipoproteins are triacylglycerols, cholesterol, cholesterol esters and phospholipids. The biosynthesis of these lipids occurs on membranes of the endoplasmic reticulum, with many of the enzymes also being present in the Golgi; the roles of these two subcellular organelles in the assembly of lipoproteins are discussed. There appears to be a compartmentalization of lipids in cells, such that defined pools, often those newly-synthesized, are preferred, or even required, for lipoprotein assembly. The process of hepatic very low density lipoprotein secretion appears to be regulated by the supply of lipids. Indeed, the synthesis of new lipid may be a major driving force in lipoprotein assembly and secretion. PMID- 2193820 TI - Lipid transport pathways in mammalian cells. AB - A major deficit in our understanding of membrane biogenesis in eukaryotes is the definition of mechanisms by which the lipid constituents of cell membranes are transported from their sites of intracellular synthesis to the multiplicity of membranes that constitute a typical cell. A variety of approaches have been used to examine the transport of lipids to different organelles. In many cases the development of new methods has been necessary to study the problem. These methods include cytological examination of cells labeled with fluorescent lipid analogs, improved methods of subcellular fractionation, in situ enzymology that demonstrates lipid translocation by changes in lipid structure, and cell-free reconstitution with isolated organelles. Several general patterns of lipid transport have emerged but there does not appear to be unifying mechanism by which lipids move among different organelles. Significant evidence now exists for vesicular and metabolic energy-dependent mechanisms as well as mechanisms that are clearly independent of cellular ATP content. PMID- 2193821 TI - Lipid transfer in plants. AB - Plant cells contain cytosolic proteins, called lipid transfer proteins (LTP), which are able to facilitate in vitro intermembrane transfer of phospholipids. Proteins of this kind from three plants, purified to homogeneity, have several properties in common: molecular mass around 9 kDa, high isoelectric point, lack of specificity for phospholipids, and binding ability for fatty acids. The comparison of their amino acid sequences revealed striking homologies and conserved domains which are probably involved in their function as LTPs. These proteins could play a major role in membrane biogenesis by conveying phospholipids from their site of biosynthesis to membranes unable to form these lipids. Immunochemical methods were used to establish an in vivo correlation between membrane biogenesis and the level of LTP or the amount of LTP synthesized in vitro from mRNAs. The recent isolation of a full-length cDNA allows novel approaches to studying the participation of LTPs in the biogenesis of plant cell membranes. PMID- 2193822 TI - Lipid transport in microorganisms. AB - Microorganisms are useful model systems for the study of intracellular transport of lipids. Eukaryotic microorganisms, such as the yeast Saccharomyces cerevisiae, are similar to higher eukaryotes with respect to organelle structure and membrane assembly. Experiments in vivo showed that transport of phosphatidylcholine between yeast microsomes and mitochondria is energy independent; transfer of phosphatidylinositol to the plasma membrane and the flux of secretory vesicles take place by different mechanisms. Linkage of transfer and biosynthesis of phospholipids was demonstrated in the case of intramitochondrial phospholipid transfer. A yeast phosphatidylinositol/phosphatidylcholine transfer protein, which is essential for cell viability, was isolated and characterized. Another phospholipid transfer protein present in yeast cytosol, which has a different specificity, is currently under investigation. Transfer of phospholipids between cellular membranes was also demonstrated with prokaryotes. The cytoplasm and the periplasma of the gram-negative facultative photosynthetic bacterium Rhodopseudomonas sphaeroides contain phospholipid transfer proteins; these seem to be involved in the biosynthesis of prokaryotic membranes. PMID- 2193823 TI - Properties and modes of action of specific and non-specific phospholipid transfer proteins. AB - We have described the mode of action of the phosphatidylcholine transfer protein (PC-TP), the phosphatidylinositol transfer protein (PI-TP) and the non-specific lipid transfer protein (nsL-TP) isolated from bovine and rat tissues. PC-TP and PI-TP specifically bind one phospholipid molecule to be carried between membranes. PC-TP, and most likely PI-TP as well, have independent binding sites for the sn-1- and sn-2-fatty acyl chains. These sites have different properties, which may explain the ability of PC-TP and PI-TP to discriminate between positional phospholipid isomers. nsL-TP, which is identical to sterol carrier protein 2, transfers all common phospholipids, cholesterol and oxysterol derivatives between membranes. This protein is very efficient in mediating a net mass transfer of lipids to lipid-deficient membranes. Models for its mode of action, which is clearly different from that of PC-TP and PI-TP, are presented. PMID- 2193825 TI - Glycolipid transfer protein and intracellular traffic of glucosylceramide. AB - Glycolipid transfer protein (GL-TP), a nonglycosylated protein with a molecular weight of 22,000 K, has been purified from pig brain. The protein transfers, by a carrier mechanism, glycolipids with a beta-glucosyl or beta-galactosyl residue directly linked to either ceramide or diacylglycerol. GL-TP appears to be present in most animal cells, and evidence has been obtained which indicates that it is a cytoplasmic protein. Little is known about the function of GL-TP. Current evidence indicates that glycosphingolipid glycosylation occurs at the luminal side of the Golgi apparatus, except for the glucosylation of ceramide, which has been shown to occur at the cytoplasmic side of the Golgi or endoplasmic membrane. It appears most likely that GL-TP participates in the intracellular traffic of glucosylceramide. PMID- 2193824 TI - Intracellular sterol trafficking. AB - Sterols are acquired by cells either biosynthetically by the interaction of cytoplasmic and endoplasmic reticulum elements, or by endocytosis. The subcellular distribution of sterols, however, argues that sterols are trafficked quickly from sites of acquisition to target membranes, particularly the plasma membrane. The mechanisms mediating this movement might include aqueous diffusion, vesicles of either a unique pathway or of the protein secretory pathway, or carrier proteins. These mechanisms are discussed and the limited data concerning each are presented. Finally, a theory is proposed which describes how sterols and other membrane reinforcing molecules might have driven the evolution of intracellular membranes, thus establishing the dynamic membrane system of modern eukaryotes. PMID- 2193827 TI - Membrane fusion. AB - The factors involved in the regulation of biological membrane fusion and models proposed for the molecular mechanism of biomembrane fusion are reviewed. The results obtained in model systems are critically discussed in the light of the known properties of biomembranes and characteristics of biomembrane fusion. Biological membrane fusion is a local-point event; extremely fast, non-leaky, and under strict control. Fusion follows on a local and most probably protein modulated destabilization, and a transition of the interacting membranes from a bilayer to a non-bilayer lipid structure. The potential role of type II non bilayer preferring lipids and of proteins in the local destabilization of the membranes is evaluated. Proteins are not only responsible for the mutual recognition of the fusion partners, but are most likely also to be involved in the initiation of biomembrane fusion, by locally producing or activating fusogens, or by acting as fusogens. PMID- 2193826 TI - Functions of fatty acid binding proteins. AB - Cytosolic fatty acid binding proteins (FABP) belong to a gene family of which eight members have been conclusively identified. These 14-15 kDa proteins are abundantly expressed in a highly tissue-specific manner. Although the functions of the cytosolic FABP are not clearly established, they appear to enhance the transfer of long-chain fatty acids between artificial and native lipid membranes, and also to have a stimulatory effect on a number of enzymes of fatty acid metabolism in vitro. These findings, as well as the tissue expression, ligand binding properties, ontogeny and regulation of these proteins provide a considerable body of indirect evidence supporting a broad role for the FABP in the intracellular transport and metabolism of long-chain fatty acids. The available data also support the existence of structure- and tissue-specific specialization of function among different members of the FABP gene family. Moreover, FABP may also have a possible role in the modulation of cell growth and proliferation, possibly by virtue of their affinity for ligands such as prostaglandins, leukotrienes and fatty acids, which are known to influence cell growth activity. FABP structurally unrelated to the cytosolic gene family have also been identified in the plasma membranes of several tissues (FABPpm). These proteins have not been fully characterized to date, but strong evidence suggest that they function in the transport of long-chain fatty acids across the plasma membrane. PMID- 2193830 TI - [Comparative characteristics of the methods of calculating numerical synaptic density in the cerebral cortex]. AB - The number of axon synaptic terminals (AT) in 1 mm3 of the acoustic (A1) and associative (field 5b) cerebral cortex in cat has been determined. Results from this determination obtained by different methods have been compared. PMID- 2193829 TI - Seroepidemiology of measles in Catalonia (Spain) 1985-1986. AB - A seroepidemiological study of measles immunological status was carried out among four different populations: schoolchildren of 6-7 years, 10-11 years and 13-14 years, and pregnant women of 18-45 years, in Catalonia, Spain; 1,213 children and 239 pregnant women were surveyed. The measurement of measles antibodies were made by indirect immunofluorescence, with antibody titres greater than or equal to 1:8 considered as positive. The prevalence of measles antibodies was 82.9% in the 6-7 year old group, 87.2% in the 10-11 year old group and 94.4% in the age group 13 14 years. Among pregnant women, the prevalence of antibodies was 96.2%. Two of the variables studied were associated with the prevalence of measles antibodies in schoolchildren: the disease antecedents and measles vaccination. In pregnant women aged 18-45 no variable had any statistically significant association with the prevalence of measles antibodies. PMID- 2193828 TI - Transmembrane movements of lipids. AB - Membranes allow the rapid passage of unchanged lipids. Phospholipids on the other hand diffuse very slowly from one monolayer to another with a half-time of several hours. This slow spontaneous movement in a pure lipid bilayer can be selectively modulated in biological membranes by intrinsic proteins. In microsomes, and probably in bacterial membranes, non-specific phospholipid flippases allow the rapid redistribution of newly synthesized phospholipids. In eukaryotic plasma membranes, aminophospholipid translocase selectively pumps phosphatidylserine (PS) and phosphatidylethanolamine (PE) from the outer to the inner leaflet and establishes a permanent lipid asymmetry. The discovery of an aminophospholipid translocase in chromaffin granules proves that eukaryotic organelles may also contain lipid translocators. PMID- 2193831 TI - [Physiologic importance of glucosamine]. AB - The paper reviews the present state of the problem on the physiological importance of D-(+)-glucosamine, an amino sugar. Glucosamine is shown to be a component of many biological important systems widely spread in nature. It is a part of the connective tissues, membranes, lipopolysaccharides and mucopolysaccharides and participates in detoxic function of the liver and kidneys. The data from literature reviewed permit concluding that glucosamine and its derivatives are potentially useful and possess antiinflammatory, liver defending, antihypoxic and other pharmacological activities. PMID- 2193832 TI - [Evaluation of the functional state of the biliary tract by dynamic echocholecystography]. AB - The state of the biliary system (BS) was estimated by the size of gallbladder on a series of its ultrasonic sections in dynamics after cholecystokinetic breakfast. Noninvasiveness, convenience, simplicity, high informativity and absence of the diagnostic ultrasound effect on the organism permit using dynamic echocholecystography (DECG) repeatedly and over a long period of time preventing appearance of any complications. Studies carried out by means of DECG proceeding from the analysis of echocholystogram plots and quantitative parameters of the motor activity cycle of the bile cyst made it possible to characterize in detail the state of basic functional elements of BS relative to the healthy organism. DECG is promising to be used for an organism with pathology of the digestive system. PMID- 2193833 TI - Infections in the compromised host. AB - The skin and/or mechanical factors, such as coughing, ciliary action or urine flow, along with phagocytes and humoral and cell-mediated immunity, help to protect the body from infection. In compromised patients, these mechanisms are impaired or bypassed, rendering patients susceptible to infection by opportunistic organisms (bacteria, mycobacteria, fungi, viruses, parasites). Mechanical barriers may be breached in patients with burns or indwelling catheters, in diabetics or cancer patients, and in parenteral drug abusers. Humoral or cell-mediated immunity may be suppressed in non-neoplastic patients following splenectomy, in diabetics, in alcoholics and in those with certain rheumatic disorders, as well as in patients undergoing haemodialysis or receiving steroids or immunosuppressive drugs. In cancer patients infection is often a cause of death, frequently occurring as a result of granulocytopenia, obstruction of natural passages, or suppression or dysfunction of humoral or cell-mediated immunity. Diagnosis of the infection may be difficult and expert advice should be sought. Treatment should be started before a conclusive diagnosis has been made, particularly in neutropenic patients since infections may be life-threatening. PMID- 2193834 TI - A multicentre study to evaluate the effect of sulbactam/ampicillin combination on anaerobic micro-organisms. AB - Ampicillin combined with the beta-lactamase inhibitor sulbactam was compared with ampicillin alone, cefoxitin and metronidazole against 569 clinical strains of anaerobic organisms. The strains included 289 species of Bacteroides, 160 strains of Clostridium and 120 strains of various species of Streptococcus/Peptostreptococus, Fusobacterium, Veillonella, Eubacterium, Bifidobacterium, Actinomyces and Propionibacterium. Sulbactam/ampicillin was as effective as cefoxitin and metronidazole against all anaerobic species tested, inhibiting more than 90% of strains at the breakpoints (16, 32 and 32 mg/l, respectively). Sulbactam/ampicillin was also significantly more active than ampicillin against strains of Bacteroides, the minimal inhibitory concentration being at least four-fold lower. In contrast, the activity of the combination did not differ from that of ampicillin alone against Fusobacterium species and Gram positive rods and cocci. PMID- 2193835 TI - Double-blind study of 5-hydroxytryptophan versus placebo in the treatment of primary fibromyalgia syndrome. AB - A double-blind, placebo-controlled study of the efficacy and tolerability of 5 hydroxytryptophan (5-HTP) was conducted in 50 patients with primary fibromyalgia syndrome. All the clinical parameters studied were significantly improved by treatment with 5-HTP and only mild and transient side-effects were reported. Further controlled studies are required to define properly the value of 5-HTP in patients with primary fibromyalgia syndrome. PMID- 2193836 TI - Cefetamet in the treatment of acute sinusitis in adult patients. AB - Cefetamet, an oral third-generation cephalosporin, was investigated in a prospective, randomized, open, comparative trial in 41 outpatients with acute sinusitis. The efficacy of 500 mg cefetamet given orally twice daily for 7 days to 22 patients was compared with that of 500 mg cefaclor given orally three times daily for 7 days to 19 patients. Sinus punctures were performed before antimicrobial therapy in 10 patients from each treatment group. A successful bacteriological response was obtained in all the 21 assessable patients treated with cefetamet and in the cefaclor-treated group 18 assessable patients were cured and two were improved, but one failed to respond to therapy. The tolerability of both drugs was good and no withdrawals from treatment were necessary. PMID- 2193837 TI - Indobufen in secondary prevention of transient ischaemic attack. Multicentre Ischaemic Attack Study Group. AB - The secondary prevention of transient ischaemic attacks was assessed in 270 patients treated orally with 100 mg indobufen given twice daily for 12 months. After 1 month's treatment, the average number and average incidence of transient ischaemic attacks were reduced significantly (P less than 0.001) and remained suppressed throughout the treatment period. Treatment was interrupted in 17 patients: in two because of side-effects (gastric disturbances); in 10 because of fatal events (six completed strokes, two myocardial infarcts and two unrelated deaths); and in five due to poor protocol compliance. Progression to reversible ischaemic neurological deficit occurred in five patients. Most side-effects were mild and transient, mainly occurring in the first month of treatment. Overall, indobufen was judged to have good efficacy and safety by both patients and physicians. PMID- 2193838 TI - A review of long-term safety data with buflomedil. AB - Tolerance of long-term buflomedil was assessed by compiling safety data (adverse effects, vital signs and clinical laboratory results) from three multicentre clinical trials in patients with intermittent claudication or Alzheimer's disease type senile dementia. The three studies were similar in design: open placebo lead in; double-blind, placebo-controlled treatment; and open long-term treatment. Patients were randomly assigned to receive 600 mg/day buflomedil given orally for 3 or 6 months (n = 297) or placebo (n = 298). Buflomedil was continued for a further 6-12 months in 193 patients and for 12 months or more in 99 patients. Side-effects occurred in 20.5% and 18.1% of buflomedil- and placebo-treated patients, respectively, with discontinuation in 14.5% and 13.1%, respectively. In the open phase, 10.9% experienced side-effects, with 1.5% of patients discontinuing treatment. Mean changes in vital signs and laboratory tests were occasionally statistically, but not clinically, significant. Overall long-term tolerance was excellent. PMID- 2193839 TI - An open, randomized comparative study of a low-strength frusemide/amiloride combination and bumetanide/potassium chloride in the treatment of mild congestive cardiac failure. AB - In an open, randomized, parallel group study lasting 8 weeks, nine males and nine females with mild congestive cardiac failure were initially treated daily with 20 mg frusemide/2.5 mg amiloride or 0.5 mg bumetanide/573 mg potassium chloride. In two patients receiving the frusemide combination and in one receiving the bumetanide combination, the daily dose was doubled after 2 weeks' treatment because of inadequate control of symptoms. Mild congestive cardiac failure symptoms (raised jugular venous pressure, oedema and dyspnoea at rest and on effort) were controlled in 9/10 patients receiving frusemide/amiloride but two patients receiving bumetanide/potassium chloride still had mild oedema after 8 weeks. Both treatments were well tolerated overall and there were no clinically significant changes in plasma electrolytes, although one patient treated with frusemide/amiloride was withdrawn due to adverse events. PMID- 2193840 TI - An open, parallel group study comparing a frusemide/amiloride diuretic and a diuretic containing cyclopenthiazide with sustained release potassium in the treatment of congestive cardiac failure--a multicentre general practice study. AB - A total of 71 patients with cardiac failure requiring diuretic treatment were randomly allocated to receive either 20 mg frusemide/2.5 mg amiloride or 0.25 mg cyclopenthiazide/8.1 mmol sustained release potassium once daily for 12 weeks. Of the 35 patients treated with cyclopenthiazide/potassium, in 47% of patients the daily dose was doubled compared with in only 30% of the 36 patients treated with frusemide/amiloride. Both treatments significantly improved crepitations, oedema, orthopnoea and patient self-assessments of dyspnoea on effort; there were no significant differences between the two treatments. Plasma potassium concentrations were unaffected by either treatment and there were no clinically significant changes in laboratory data. Of the five patients receiving frusemide/amiloride and of the eight receiving cyclopenthiazide/potassium who withdrew from the trial, three and four, respectively, were due to possible drug related effects. It is concluded that frusemide/amiloride is efficacious and acceptable for the treatment of congestive heart failure. PMID- 2193841 TI - Cell-specific regulation of progesterone receptor in the female reproductive system. PMID- 2193842 TI - Structure, function and transforming potential of the epidermal growth factor receptor. PMID- 2193843 TI - Use of statistical decision rules for evaluating laboratory animal carcinogenicity studies. AB - In the evaluation of long-term rodent carcinogenicity studies, many different tumor sites and types are evaluated, which may increase the likelihood of a statistical false positive. To deal with this issue, a number of statistical decision rules have been proposed that take into account multiple comparisons. This paper discusses the various types of decision rules and evaluates the factors that may lead to different interpretations of experimental results. These concepts are illustrated by examining the statistical decision procedures used by three analysts to evaluate the results of 25 long-term rodent carcinogenicity studies carried out by the National Cancer Institute. Agreement among these decision rules is shown to be greater than originally reported. It is also concluded that while the application of statistical decision rules may be of value in some instances to guard against statistical false positives, the final interpretation of the data should be based on biological as well as statistical considerations. Thus, statistical decision rules should not be employed as a substitute for sound scientific judgment in the overall evaluation of these experiments. PMID- 2193844 TI - Toxicological information series, II. A survey of toxicology information. AB - The structure of toxicology information is outlined. Key resources, both print and electronic, are described and the role of organizations is discussed on national and world levels. The section on computerized information covers systems such as TOXNET, CIS, and the ANSWER workstation. PMID- 2193845 TI - Long-term alteration of adult bone marrow colony formation by prenatal chlordane exposure. AB - Female mice were treated with either 0, 4, or 8 mg of chlordane per kilogram body weight daily for 18 days during pregnancy. The offspring of these mice were assayed for bone marrow hematopoietic activity at 100 and 200 days of age. Hematopoietic activity was evaluated for in vitro granulocyte-macrophage colony forming units (GM-CFU) and in vivo spleen CFU (CFU-S). The consistent finding was a significant depression both of the numbers of bone marrow GM-CFU and of the CFU S in offspring exposed to either 4 or 8 mg/kg chlordane even at 100 and 200 days after cessation of treatment. Prenatal treatment with chlordane did not affect the number of recoverable viable bone marrow cells at either of these time points. Ontological development was selectively affected by chlordane exposure, since subchronic (18 day) treatment of adult mice did not significantly alter bone marrow GM-CFU or CFU-S levels. These data suggest that the decreased delayed type hypersensitivity reactions noted previously in mice exposed to chlordane prenatally may be due to a change in the functional capacity of myeloid lineage cells rather than altered T cell function. PMID- 2193846 TI - [The erythron system in burns]. PMID- 2193847 TI - Overproduction of the yeast STE12 protein leads to constitutive transcriptional induction. AB - Haploid a and alpha cells of the yeast Saccharomyces cerevisiae respond to the pheromones alpha- and a-factor, respectively, by increasing transcription of inducible genes, arresting cell division, and forming cell-surface projections. These responses are dependent on the activity of several genes, including STE12, whose product binds to the pheromone response element located within the regulatory DNA sequences of inducible genes. We assayed the effects of overproducing the STE12 protein in both STE+ cells, as well as ste2, ste7, and ste11 mutant cells. We find that overproduction leads to increased transcription of pheromone-inducible genes and is able to suppress the mating defect of the ste mutants. These results suggest that one effect of pheromone treatment may be to increase the ability of the STE12 protein to activate transcription. In addition, we observed that cells cannot tolerate very high levels of the STE12 protein, and many arrest in G1 with a large size and morphological changes. Thus, constitutively high-level transcription of pheromone-inducible genes causes cells to display some features similar to treatment with pheromone. PMID- 2193848 TI - Irradiation cataract in children after bone marrow transplantation. AB - Chemotherapy and radiation produce a dose-dependent anti-leukemic effect. Combined chemoradiotherapy and bone marrow transplantation (BMT) were given in our clinic to treat children with acute leukemias. Total body irradiation of 10 Gy in a single dose was used. One long-term side effect of this treatment was the development of subcapsular cataract; this was seen in all nine long-term survivors of the 17 children with acute lymphoblastic (ALL) or acute myelogenous (AML) leukemia who were treated as described above. One year after marrow transplantation, all the eyes studied had visual acuity of 20/20 and an optically clear lens. Three years later, 60% of the eyes had visual acuity of less than 20/40 and all had posterior, subcapsular cataracts. The cataract in all cases was quite uniform, consisting of opacities in the posterior subcapsular region. Cataract formation was treatment-related and seemed to correlate only to the type of total body irradiation. We concluded that the cataracts seen in the present study were a late complication of allogeneic BMT and were specifically due to the single-dose total body irradiation. PMID- 2193849 TI - The effect of short versus long exposure times of argon laser panretinal photocoagulation on proliferative diabetic retinopathy. AB - We performed a randomized clinical trial comparing short-duration (0.1 s) with long-duration (0.5 s) blue-green argon laser burns to deliver panretinal photocoagulation (PRP) in eyes suffering from proliferative diabetic retinopathy with high risk characteristics. We studied 19 eyes in the 0.1-s group and 24 eyes in the 0.5-s group for 6 months. Two or more lines of acuity were lost by 20% of the 0.1-s PRP eyes, but by only 8% of the 0.5-s PRP eyes; New or increased vitreous hemorrhages occurred in 30% of the 0.1-s PRP eyes, but in only 16% of the 0.5-s PRP eyes; New or increased traction retinal detachments did not occur in the 0.1-s PRP eyes, but occurred in 16% of the 0.5-s PRP eyes. There was complete disc neovascular regression in 85% of the 0.1-s PRP eyes and 81% of the 0.5-s PRP eyes. These trends were not statistically significant. PMID- 2193850 TI - Autoantibodies to retinal astrocytes associated with age-related macular degeneration. AB - Sera from 128 patients with age-related macular degeneration (AMD) were examined and profiles of a variety of serum constituents, including immunoglobulins, alpha and beta globulins and autoantibodies, were tabulated. A similar series of tests were carried out on 20 control sera. The results indicate a higher incidence of serum abnormalities, particularly involving alpha-2 globulin, in patients with disturbance of pigmentation of the retinal pigment epithelium (RPE). The sera were further tested for the presence of autoantibodies with specificity for retinal tissue, and five major staining patterns were observed. Many sera produced patterns of labelling on human retina identical to that observed using labelled monoclonal anti-glial fibrillary acid protein (GFAP) antibodies, which are an established marker of retinal astrocytes. Although anti-retinal autoantibodies have been reported in association with a number of ocular pathologies, the observation of anti-astrocyte autoantibodies is new. Astrocytes are involved in the maintenance of the blood-retinal barrier (BRB) and also appear to be the facultative antigen-presenting cells of neural tissue. The present results indicate that the formation of anti-astrocyte autoantibodies may be an early feature of the pathogenesis of AMD. PMID- 2193851 TI - [The long-term neurotoxic action of organophosphorus pesticides (review)]. PMID- 2193852 TI - Mitochondrial mutations may increase oxidative stress: implications for carcinogenesis and aging? AB - The sensitivity of mitochondrial DNA to damage by mutagens predisposes mitochondria to injury on exposure of cells to genotoxins or oxidative stress. Damage to the mitochondrial genome causing mutations or loss of mitochondrial gene products, or to some nuclear genes encoding mitochondrial membrane proteins, may accelerate release of reactive species of oxygen. Such aberrant mitochondria may contribute to cellular aging and promotion of cancer. PMID- 2193853 TI - Suggested mechanisms for the production of 4-hydroxy-2-nonenal from the autoxidation of polyunsaturated fatty acids. AB - Autoxidation of certain polyunsaturated fatty acids (PUFA) produces 4-hydroxy-2 nonenal (HNE). Of all of the many products produced during PUFA autoxidation, HNE is one of the more interesting. It is remarkably cytotoxic, and appears to play a role in certain types of pathology. This manuscript suggests, for the first time, mechanisms that rationalize the production of HNE from PUFA that undergo autoxidation. The mechanisms require, in agreement with the facts, an n-6 fatty acid and iron catalysis. PMID- 2193854 TI - The participation of coenzyme Q in free radical production and antioxidation. AB - Published experimental data pertaining to the participation of coenzyme Q as a site of free radical formation in the mitochondrial electron transfer chain and the conditions required for free radical production have been reviewed critically. The evidence suggests that a component from each of the mitochondrial NADH-coenzyme Q, succinate-coenzyme Q, and coenzyme QH2-cytochrome c reductases (complexes I, II, and III), most likely a nonheme iron-sulfur protein of each complex, is involved in free radical formation. Although the semiquinone form of coenzyme Q may be formed during electron transport, its unpaired electron most likely serves to aid in the dismutation of superoxide radicals instead of participating in free radical formation. Results of studies with electron transfer chain inhibitors make the conclusion dubious that coenzyme Q is a major free radical generator under normal physiological conditions but may be involved in superoxide radical formation during ischemia and subsequent reperfusion. Experiments at various levels of organization including subcellular systems, intact animals, and human subjects in the clinical setting, support the view that coenzyme Q, mainly in its reduced state, may act as an antioxidant protecting a number of cellular membranes from free radical damage. PMID- 2193855 TI - Free radicals, antioxidant enzymes, and carcinogenesis. AB - Free radicals are found to be involved in both initiation and promotion of multistage carcinogenesis. These highly reactive compounds can act as initiators and/or promoters, cause DNA damage, activate procarcinogens, and alter the cellular antioxidant defense system. Antioxidants, the free radical scavengers, however, are shown to be anticarcinogens. They function as the inhibitors at both initiation and promotion/transformation stage of carcinogenesis and protect cells against oxidative damage. Altered antioxidant enzymes were observed during carcinogenesis or in tumors. When compared to their appropriate normal cell counterparts, tumor cells are always low in manganese superoxide dismutase activity, usually low in copper and zinc superoxide dismutase activity and almost always low in catalase activity. Glutathione peroxidase and glutathione reductase activities are highly variable. In contrast, glutathione S-transferase 7-7 is increased in many tumor cells and in chemically induced preneoplastic rat hepatocyte nodules. Increased glucose-6-phosphate dehydrogenase activity is also found in many tumors. Comprehensive data on free radicals, antioxidant enzymes, and carcinogenesis are reviewed. The role of antioxidant enzymes in carcinogenesis is discussed. PMID- 2193856 TI - Comparison of ceftriaxone (1 x 1 g/day) versus cefotaxime (3 x 1 g/day) for gynecologic and obstetric infections. A randomized clinical trial. AB - A prospective, randomized clinical trial was conducted to compare the efficacy and tolerance of a single dose of 1 g ceftriaxone i.v. daily with 3 doses of 1 g cefotaxime i.v. daily for obstetric and gynecologic infections. Both agents are characterized by a wide spectrum and potent activity. Furthermore, ceftriaxone has an outstanding serum half-life of 8 h. 41 patients with pelvic inflammatory disease, pelvic or wound infections after vaginal or abdominal hysterectomy, endomyometritis and urinary-tract infection were included. Patients were monitored clinically by routine laboratory methods (erythrocyte sedimentation rate, white blood cell count and cross-reacting protein) and bacteriologically. Clinical parameters of infection were fever, local pain and/or tenderness, a sactosalpinx or pyosalpinx at palpation and cervical secretion. Clinical cure was achieved in 77.3% in the ceftriaxone and in 78.9% in the cefotaxime group, improvement in 3 (13.6%) and 4 patients (21.0%), respectively. 2 clinical failures were seen in the ceftriaxone group. One was a severe pelvic infection following vaginal hysterectomy, which responded to the addition of metronidazole, the other was due to a chlamydial salpingitis, which was cured with a 10-day course of doxycycline. Both antibiotics were well tolerated. Our results suggest that for obstetric and gynecologic infections a single 1-gram dose of ceftriaxone is equally effective as three 1-gram doses of cefotaxime. PMID- 2193857 TI - Estrogen and progesterone receptors in the human thymus. AB - Thymus tissue samples from 8 prepubertal children of both sexes were analyzed for estrogen and progesterone receptors. With the use of an enzyme immunoassay, estrogen receptors in both the cytosol and nuclear fraction were detected. The mean concentration (+/- SD) of receptors in the cytosol fraction was 2.1 +/- 0.9 and for the sum of receptors in both fractions 2.8 +/- 1.0 fmol/mg of protein. In addition low concentrations of progesterone receptors (mean value +/- SD = 0.9 +/ 0.3 fmol/mg of protein) were detected in all investigated samples. The presence of estrogen receptors in the nuclear fraction and of progesterone receptors suggests that the estrogen receptors may be active in mediating a physiological response and thus supports the view that the human thymus is a target organ for estrogens. PMID- 2193858 TI - Prevention of a side effect of epidural morphine by epidural steroid administration in cesarean section. AB - In order to evaluate the effect of preventive corticosteroid on the occurrence of pruritus after epidural anesthesia with morphine, we studied 95 patients undergoing cesarean section. Thirty-seven patients (group I) were given 20 mg of bupivacaine 0.5% for the operation and 2 mg of morphine hydrochloride with 50 mg of Ultracortene-H immediately after the operation and 24 h later, and 58 patients (group II) were given epidural bupivacaine during the operation and epidural morphine hydrochloride immediately after the operation and 24 h later without Ultracortene-H. Only 8.1% of group I patients had pruritus after the injection compared to 20.6% in group II. We suggest that the addition of 50 mg Ultracortene H to 2 mg epidural morphine analgesia after the operation might prevent severe forms of pruritus. PMID- 2193859 TI - Haematocervix after conization diagnosed by ultrasonography. AB - Haematocervix is an uncommon complication after conization. This report deals with 1 case that presented with clinical signs of progressive stenosis and was diagnosed by ultrasonography. Based on analysis of the 3 previously reported cases the pathogenesis of this condition is discussed. PMID- 2193860 TI - Determination of deslanoside in antemortem and postmortem specimens. Unusual case report. AB - One case of the erroneous administration of deslanoside and high level of drug in antemortem plasma and postmortem specimens has been reported owing to the unusual surrounding circumstances. Deslanoside in antemortem plasma was determined by FPIA and the analysis was done by HPLC in the postmortem tissue samples. The analytical results and methods used in the examinations are discussed in the following paper. PMID- 2193861 TI - Pulmonary fibrosis. AB - Diffuse interstitial pulmonary fibrosis is the end result of alveolar damage which may occur as a sudden acute incident or as a slowly developing process. Potentiating factors include release of enzymes and generation of oxygen radicals by granulocytes. Evidence from studies on broncho-alveolar lavage fluid and from immunocytochemistry indicate that an autoimmune process has an important but, as yet, not clearly defined role in initiating the disease. The fibrosis is probably due to proliferation of small clones of fast growing fibroblasts of a specific phenotype. Bronchiolitis obliterans, organizing pneumonia, idiopathic pulmonary fibrosis, usual interstitial pneumonia and desquamative interstitial pneumonia represent different aspects of the same condition. Their varied morphological appearances probably reflect the fact that tissue has been taken at different stages in the development of the disease. PMID- 2193862 TI - The distribution of renin-containing cells in kidneys with renal artery stenosis- an immunocytochemical study. AB - In 10 kidneys removed for hypertension due to renal artery stenosis, the histological appearances varied from negligible ischaemic damage to end-stage ischaemic atrophy. We stained the renin-containing cells in tissue sections using an antiserum to pure human renin and an immunoperoxidase technique. In all kidneys there was hyperplasia of the renin-containing cells both in juxtaglomerular apparatuses (JGAs) and in arteries outside the JGA, where these cells extended proximally as far as the interlobular arteries. We mapped the distribution of renin-containing cells and found them in all zones of the renal cortex; in three kidneys they were predominantly in the superficial cortex; in four they were distributed more evenly throughout the width of the cortex; but in three kidneys the normal gradient was reversed, with most of the cells being in the juxtamedullary cortex and, in two of the cases, little or no stainable renin in the superficial cortical JGAs. We suggest that these abnormalities in the distribution of renin-containing cells could affect both the pattern of intrarenal blood flow and the site in the kidney at which secreted renin enters the blood. PMID- 2193863 TI - The spectrum of chronic periaortitis. AB - A review of the histology of 440 sections of atherosclerotic aortas and arteries showed that 85% contained advanced atherosclerotic plaques. Of these, 92% showed some degree of adventitial inflammation with subclinical chronic periaortitis in 49%. A review of 20 cases of clinical chronic periaortitis, which included 12 cases of inflammatory aneurysm and 8 cases of idiopathic retroperitoneal fibrosis, showed that there were no significant differences between them apart from an increase in aortic diameter in the former. The term chronic periaortitis is appropriate for the spectrum of subclinical and clinical forms of chronic adventitial inflammation associated with advanced atherosclerosis and medial thinning. PMID- 2193864 TI - Beta-2-microglobulin expression in relation to amplification of oncogenes and prognosis in breast carcinoma. PMID- 2193865 TI - Ivalon (polyvinyl alcohol) sponge presenting as an extrarectal mass. PMID- 2193866 TI - Oncocytomas. PMID- 2193867 TI - A historical review of the Madison model of community care. AB - The community-based mental health care programs developed by Stein, Test, and their colleagues in Madison, Wisconsin, have had a profound impact on the delivery of mental health services to the severely mentally ill. The authors trace the development of the model from its late-1960s emphasis on improving Mendota State Hospital and providing intensive post-discharge care through the phases of releasing patients early to the community, preventing hospitalization, providing continuous community care for young schizophrenics, maintaining difficult patients in the community, and organizing a system of care. Throughout its evolution the model has changed significantly in response to changing circumstances, reflecting the assertive adaptability of the approach. Program planners attempting to incorporate elements of the Madison model in their own settings must be aware of current pressures that are likely to force further adaptations. PMID- 2193868 TI - Assertive community treatment: an evaluation of the experimental evidence. AB - Experimental studies of assertive community treatment programs based on the Training in Community Living model are reviewed. In most of the programs studied, interdisciplinary treatment teams met with patients in the community, taught them to take care of basic needs, and ensured that they received adequate material support and medical care. Across the service settings and patient populations studied, assertive community treatment reduced hospital utilization. Although early researchers provided evidence that the approach was more effective than conventional treatment in controlling symptoms, promoting social functioning, and improving occupational performance, recent studies have generally not replicated these findings. Defining the conditions under which assertive community treatment achieves superior functional outcomes remains an important challenge for future research. PMID- 2193869 TI - Teaching hospitals brace for huge GME payment losses. PMID- 2193870 TI - Adopting Deming's quality improvement ideas: a case study. AB - Much has been written about quality guru W. Edward Deming's quality improvement ideas. But how can his concepts be applied to a health care setting? Michael Pugh, CEO of Parkview Episcopal Medical Center, Pueblo, CO, and key members of his staff talked with Hospitals about what happened when they applied Deming's ideas at their hospital. PMID- 2193871 TI - Gradison stresses Medicare vulnerability. PMID- 2193872 TI - Geriatric psych shortages slow growth of services. PMID- 2193873 TI - The 1988 Bethesda System for reporting cervical/vaginal cytologic diagnoses: developed and approved at the National Cancer Institute Workshop in Bethesda, Maryland, December 12-13, 1988. PMID- 2193874 TI - Changes in mitotic rate and cell cycle fractions caused by delayed fixation. AB - The mitosis frequency and flow cytometric data of malignant neoplasms are important, both for diagnosis and for prognosis. It is unclear to what extent these factors are affected by a delay in the fixation of tumor biopsies. We have thus studied the mitotic activity and DNA content in human soft-tissue sarcoma xenotransplants, fixed for periods of 5 minutes and 3, 6, 9 and 12 hours after biopsy. On average, the mitoses counted by two observers were 13% and 10% below initial values after 3 hours, and decreased by 46% and 39% after 12 hours. The mitosis decrease was related to the degree of mitotic activity of individual tumors, and was minimal in the sarcomas with the lowest mitotic rate. These results were reproducible. However, numerous pyknotic mitotic figures were observed, so the decrease in counts is largely due to their reduced identifiability, and only partly attributable to a completion of the cell cycle. Well-preserved mitotic figures demonstrable after 12 hours appear to indicate that the proliferation activity only gradually decreases in unfixed biopsies. The flow cytometric data did not change substantially; only a slight increase in the G2 + M-phase fraction was observed. General conclusions from the results are limited by the fact that the investigated sarcomas had a higher mitotic activity than most carcinomas. Nevertheless, early fixation of biopsies is desirable to accurately measure mitosis counts for the grading of malignancy. PMID- 2193875 TI - Malignant epithelioid pleural mesothelioma versus peripheral pulmonary adenocarcinoma: a histochemical, ultrastructural, and immunohistologic study of 103 cases. AB - The distinction between malignant epithelioid pleural mesothelioma (MEPM) and peripheral adenocarcinoma of the lung with pleural invasion (PAL) continues to represent a diagnostic challenge in selected cases. In order to provide comparative data on histologic, histochemical, and immunohistochemical features of these neoplasms, we analyzed 51 ultrastructurally categorized MEPMs and 52 PALs with the periodic acid-Schiff-diastase (PAS-D), mucicarmine, and colloidal iron stains, and a panel of immunohistologic reagents. Antibodies to cytokeratin, vimentin, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), Leu M1, the B72.3 antigen, blood group isoantigens (BGI), placental alkaline phosphatase, amylase, S100 protein, and Clara cell antigen were used, as applied to paraffin sections with the avidin-biotin-peroxidase complex technique. Ultrastructural studies revealed long, branching microvilli in MEPM cells in all cases, with length-to-diameter ratios (LDR) of 10:1 or more. In contrast, PAL manifested short, nonbranching microvilli with LDR of 8:1 or less. Reactivity with PAS-D and mucicarmine stains was strictly confined to PAL, and hyaluronidase sensitive colloidal iron-positivity was restricted to MEPM. However, only 63% and 41% of these respective neoplasms demonstrated such histochemical reactivity. Immunohistologic results correlated well with electron microscopic classification. All MEPMs and PALs were reactive for cytokeratin; in addition, the majority of tumors in each group expressed EMA, and a minority were reactive for vimentin. In adenocarcinomas of the lung, Leu M1 was observed in all cases, CEA was apparent in 96%, B72.3 labeled 84%, and BGI were present in 67%; all PALs expressed at least two of these determinants, but none was seen in any mesothelioma. The other markers included in this study also were observed in some PAL cases, but not in MEPM. These findings suggest that immunohistology parallels electron microscopy in efficacy in the diagnostic separation of MEPM and PAL. Using antibodies to Leu M1, CEA, and the B72.3 antigen, reactivity for at least two of these three markers appears to exclude a diagnosis of pleural mesothelioma. The other glycoproteinaceous, oncoplacentofetal, and cytoplasmic antigens we studied can be used to reinforce such a determination, since their distribution is confined to adenocarcinomas. PMID- 2193876 TI - Immunohistochemical and ultrastructural studies of twelve argentaffin and six argyrophil carcinoids of the appendix vermiformis. AB - Endocrine cell types in 12 argentaffin and six argyrophil carcinoids and in nonneoplastic epithelia of the appendix vermiformis were investigated histochemically, immunohistochemically, and ultrastructurally. The nonneoplastic epithelia contained serotonin (Ser), peptide YY (PYY), glicentin (Gli), neurotensin (Neu), and somatostatin (So) cells in decreasing frequency. Out of 30 nonneoplastic Ser cells examined ultrastructurally, 28 cells were EC1 cells and two were non-EC cells. Eleven of 12 argentaffin carcinoids could be immunostained with anti-Ser serum and all of those 11 were composed almost totally of Ser cells. One of the 11 contained a small number of Neu cells. Ultrastructurally, 11 argentaffin carcinoids were composed predominantly of EC1 and/or ECn cells, and one was composed primarily of non-EC cells. Out of the six argyrophil carcinoids, five were argyrophil, non-argentaffin carcinoids; three consisted almost totally of PYY cells; one consisted of 60% PYY cells, 40% So cells and a few Gli cells; and one consisted of Ser cells alone. Ultrastructurally, the first four of those tumors were composed of D1 and/or L cells and the latter tumor was composed of ECn cells. The remaining one argyrophil carcinoid contained a few Ser-positive argentaffin cells and consisted almost totally of ECn cells which were found in both parts, with and without argentaffinity. It is concluded that the appendiceal carcinoids comprise two distinct groups on the basis of the main constituting cell type: Ser-positive, argentaffin carcinoids, composed of EC cells and peptide (especially of PYY)-positive, and Ser-negative, argyrophil non-argentaffin carcinoids of D1 and/or L cells. PMID- 2193877 TI - Antenatal ultrasonic diagnosis of Potter's syndrome. PMID- 2193878 TI - Androgen treatment of constitutional growth delay in adolescent males. PMID- 2193880 TI - Transcutaneous oxygen monitoring in neonates. PMID- 2193881 TI - Lower-body suction and cardiovascular reflexes: physiological and applied considerations. AB - Lower body subatmospheric pressure (LBSP) can be applied in a graded manner to a supine subject enclosed in a box upto the level of the iliac crest in order to elicit cardiovascular reflexes without a change of posture, and without a gravity induced shift of the central blood volume into the periphery. The procedure effectively produces a controlled, non-haemorrhagic hypovolaemia. The method may be used to differentiate the reflex cardiovascular effects induced by the deactivation of the low-pressure cardiovascular receptors (LBSP less than 30mmHg), and those produced by the deactivation of the arterial baroreceptors (LBSP greater than 30 mmHg). The former results in an increase in the limb vascular resistance without a change in heart rate and blood pressure, while the latter produces a tachycardia, an increase in the diastolic BP with a fall in the sytolic BP. The CVP and the cardiac output reduce with increasing suction. Cardiovascular reflex effects of -40 mmHg are similar to those produced by a change of posture from supine to standing. Vaso-vagal syncope appears with increasing frequency when LBSP exceeds -60 mmHg even in the normal subjects. The test is useful in the aeromedical assessment of apparently normal individuals with low orthostatic tolerance, in the evaluation of the effects of physiological and pharmacological interventions on cardiovascular reflexes, and in the evaluation of patients of autonomic neuropathies. LBSP is also a means of inducing safe, well controlled syncope in order to study the genesis of this phenonmenon. PMID- 2193882 TI - Instructive case: subpulmonic pleural effusion. PMID- 2193884 TI - Isoniazid--the pivot of chemotherapy in tuberculosis. PMID- 2193883 TI - Ultrasonic intrauterine growth curves. AB - Intrauterine growth was studied by serial ultrasonic measurements of biparietal diameter (BPD), femur length (FL) and abdominal circumference (AC) in 241 normal low risk obstetric patients. These measurements were used to construct normal ultrasonic fetal weight and length curve. The data correlate well with the already established, postnatal weight and length curves after 28 weeks of gestation. The fetal ponderal index curve was compared with postnatal ponderal index curves available. Antenatal recognition of fetal weight, length and ponderal index can be used to evaluate pregnancies at risk for altered fetal growth. PMID- 2193885 TI - Clinico-bacteriological study of Salmonella meningitis. PMID- 2193879 TI - Antibody mediated targeting of radioisotopes, drugs and toxins in diagnosis and treatment. AB - The recent resurgence of interest in site specific delivery of radioisotopes, chemotherapeutic drugs and toxins for the diagnosis and treatment of cancer, and for the selective manipulation of the immune system, can be directly related to the need for improved diagnosis and the fact that for many cancers, for example lung, colon and gastric, the conventional treatments of surgery, radiotherapy and chemotherapy have reached a plateau in terms of the number of patients cured. To date, because of their specificity, the major emphasis has been on the use of antibodies as carriers and extensive in vitro, in vivo preclinical and clinical evaluation is underway. The aim of this article is to review recent progress, highlight avenues being explored to overcome limitations and to indicate new approaches that are evolving in antibody mediated targeting. PMID- 2193886 TI - Prenatal diagnosis of achondrogenesis. PMID- 2193887 TI - Acute hydrops of the gallbladder. PMID- 2193888 TI - Antipyretics in pediatric practice. PMID- 2193889 TI - Metabolism of branched-chain amino acids and ammonia during exercise: clues from McArdle's disease. AB - Patients with McArdle's disease (myophosphorylase deficiency) cannot use muscle glycogen as an energy source during exercise. They therefore are an ideal model to learn about the metabolic adaptations which develop during endurance exercise leading to glycogen depletion. This review summarizes the current knowledge of ammonia and amino acid metabolism in these patients and also adds several new data. During incremental exercise tests in patients with McArdle's disease, forearm venous plasma ammonia concentration rises to a value between 200 and 500 microM. Femoral arteriovenous difference studies show that muscle produces the ammonia. The leg release of both ammonia and glutamine (in mumol/min) has been estimated to be five- to tenfold larger in one of these patients than in healthy individuals exercising at comparable relative work load. Patients with McArdle's disease have a larger uptake of branched-chain amino acids (BCAA) by exercising leg muscles and show a more rapid activation of the muscle branched-chain 2-oxo acid dehydrogenase complex, a key enzyme in the degradation of the BCAA. In general, supplements of BCAA taken before the exercise test lead to a deterioration of exercise performance and a higher increase in heart rate and plasma ammonia during exercise, whereas supplements of branched-chain 2-oxo acids improve exercise performance and lead to a smaller increase in heart rate and plasma ammonia. At constant power output, patients with McArdle's disease show a rapid increase in heart rate and exertion perceived in the exercising muscles, which peak within 10 min after the start of exercise and then fall again ("second wind"). Peak heart rate and peak exertion coincide with a peak in plasma ammonia. Ammonia production during exercise in these patients is estimated to exceed the reported breakdown of ATP to IMP and therefore most likely originates from the metabolism of amino acids. Deamination of amino acids via the reactions of the purine nucleotide cycle and glutamate dehydrogenase are possible pathways. Deamination of glutamine, released by muscle, by glutaminase present in the endothelial cells of the vascular system may also contribute to the ammonia production. The observations made in these patients have led to the hypothesis that excessive acceleration of the metabolism of BCAA drains 2-oxoglutarate in the primary aminotransferase reaction and thus reduces flux in the citric acid cycle and impedes aerobic oxidation of glucose and fatty acids. This draining effect is normally counteracted by the anaplerotic conversion of muscle glycogen to citric acid cycle intermediates, a reaction which is severely hampered in these patients due to the glycogen breakdown defect.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2193890 TI - A communicational link between skeletal muscle, brain, and cells of the immune system. AB - The present paper reviews evidence for the role of specific amino acids in the etiology of fatigue and the overtraining syndrome in athletes. An increase in the plasma concentration ratio of free tryptophan: branched-chain amino acids may mediate an increase in 5-HT synthesis in the brain and thus induce fatigue during exercise. Glutamine is essential for the proper functioning of cells of the immune system and a decrease in plasma glutamine concentration post-exercise and in overtraining may induce an impairment in immune function. Branched-chain amino acids may play a central role in both these processes. Thus, they compete with free tryptophan for entry into the brain. Branched-chain amino acids may also be important precursors of nitrogen for the synthesis of glutamine in skeletal muscle or important in the control of glutamine release from muscle. Consequently, the metabolism of glutamine, tryptophan, and branched-chain amino acids may be the key to understanding some aspects of central fatigue and some aspects of immunosuppression that are very relevant to athletic endeavor. They may be also relevant to other physiological and pathological conditions. PMID- 2193891 TI - Exercise-induced hyperammonemia: peripheral and central effects. AB - The intent of this paper is to review the recent literature on exercise-induced hyperammonemia (EIH) and to compare the current interpretations of ammonia accumulation during exercise with the recognized clinical symptoms of progressive ammonia toxicity. In doing so, we will speculate on possible exercise-induced symptoms of CNS dysfunction which could result from elevated ammonia during intense short-duration or prolonged exercise. Ammonia is a ubiquitous metabolic product producing multiple effects on physiological and biochemical systems. Its concentration in several body compartments is elevated during exercise, predominantly by increased activity of the purine nucleotide cycle (PNC) in skeletal muscle. Depending on the intensity and duration of exercise, muscle ammonia may be elevated to the extent that it leaks (diffuses) from muscle to blood, and thereby can be carried to other organs. The direction of movement of ammonia or the ammonium ion is dependent on concentration and pH gradients between tissues. In this manner, ammonia can also cross the blood-brain barrier (BBB), although the rate of diffusion of ammonia from blood to brain during exercise is unknown. It seems reasonable to assume that exhaustive exercise may induce a state of acute ammonia toxicity which, although transient and reversible relative to disease states, may be severe enough in critical regions of the CNS to affect continuing coordinated activity. Regional differences in brain ammonia content, detoxification capacity, and specific sensitivity may account for the variability of precipitating factors and latency of response in CNS-mediated dysfunction arising from an exercise stimulus, e. g., motor incoordination, ataxia, stupor. There have been numerous suggestions that elevated ammonia is associated with, or perhaps is responsible for, exercise fatigue, although evidence for this relies extensively on temporal relationships. Fatigue may become manifest both as a peripheral organ or central nervous system phenomenon, or combination of both. Thus, we must examine the sequential or concomitant changes in ammonia concentration occurring in the periphery, the central nervous system (CNS), and the cerebrospinal fluid (CSF) induced by any effector, not only exercise, to interpret and rationalize the diverse physical, physiological, biochemical, and clinical symptoms produced by hyperammonemic states. Since more is known about elevated brain ammonia during other diverse conditions such as disease states, chemically induced convulsion, and hyperbaric hyperoxia, some of these relevant data are discussed. PMID- 2193892 TI - The purine nucleotide cycle revisited [corrected]. AB - This review is restricted to the operation of the purine cycle in mammalian muscle. A previous review provided a summary of early evidence for the operation of the cycle and of various functions proposed for the cycle. It also provided a brief history of work on ammonia production by muscle and other tissues and of the discovery of the enzymes of the purine nucleotide cycle. Recent reviews on the purine nucleotide cycle include those of Terjung et al. and van Waarde. PMID- 2193893 TI - Adenine nucleotide degradation in striated muscle. AB - Adenine nucleotides play a central role in cellular processes involving the transduction of energy. Among striated muscles, the management of adenine nucleotide catabolism differs greatly. These differences can be understood by considering the distribution, activity, and kinetic characteristics of degradative enzymes. When these factors are weighed in light of the differing energetic demands faced by heart and skeletal muscle fiber types, a coherent picture emerges. Our analysis suggests that, as the routine energy demand of a particular muscle rises in relation to the tissue's capacity for oxidative metabolism, the pattern of adenine nucleotide degradation shifts toward increased rates of AMP deamination along with lessened rates of dephosphorylation. PMID- 2193894 TI - The Chinese foot-binding syndrome. Observations on the history and sequelae of wearing ill-fitting shoes. PMID- 2193895 TI - Parapsoriasis. A century later. PMID- 2193896 TI - Acrokeratoelastoidosis. AB - Two cases of acrokeratoelastoidosis comprised of smooth shiny papules on the hands, feet and legs, are reported. Focal acral hyperkeratosis, degenerative collagenous plaques of the hands and keratoelastoidosis marginalis of the hands are three closely related conditions. PMID- 2193897 TI - A desktop expert system for the differential diagnosis of dementia. An evaluation study. AB - EVINCE-I is a desktop expert system for the differential diagnosis of dementia, implemented on a personal computer. It is intended to assess the effectiveness of this new technology in modeling a psychiatrist who uses international guidelines for diagnosing dementia. EVINCE-I was tested in diagnosing 19 patients with varying stages of dementia and 10 patients showing other disorders except dementia. EVINCE-I and the human expert were in perfect agreement on the diagnosis of dementia and correlated highly on the diagnosis of dementia of the Alzheimer type and multiple infarct dementia. EVINCE-I thus offers important possibilities as a tool in investigating the data and procedures used by the human expert. PMID- 2193898 TI - A consensus development conference on the practice of platelet transfusion in The Netherlands. PMID- 2193899 TI - Myth, medicine and music. PMID- 2193900 TI - Disodium pamidronate, bisphosphonate for malignant hypercalcaemia. PMID- 2193901 TI - Extraction, purification and characterization of ADH1 from the budding yeast Kluyveromyces marxianus. AB - The enzyme ADH1 has been extracted and purified from the budding yeast Kluyveromyces marxianus, and its enzymatic activity has been compared, with the ADH1 extracted and purified in the same way from the well known yeast Saccharomyces cerevisiae. K. marxianus ADH1 has an optimal temperature higher than the S. cerevisiae enzyme (45-50 degrees vs 35 degrees C), a better stability to pH variations in the oxidative reaction (pH optimum 7.5), a lower Michaelis constant for acetaldehyde, and a good catalytic activity both for fermentative and oxidative reactions. In fact, while in Saccharomyces the constants ratio (velocity constant fermentation/velocity constant oxidation) is about 20,000, in Kluyveromyces the same ratio is only 15. Even if these two Genera are quite related (they belong to the same subfamily) it seems that their ADH1s possess different catalytic properties. PMID- 2193902 TI - Aphasia due to lesions confined to the right hemisphere in right handed patients: a review of the literature including the Italian cases. AB - We review most of the work published, to our knowledge, between 1880 and 1988 on aphasia due to right cerebral lesions in right-handed patients ("crossed aphasia"). We summarize the 87 cases found in chronological order within defined groups, dealing in greater detail with the less well-known cases in English language publications and with the cases from other sources that we consider most representative and convincing. The 87 cases fall into three groups on the following criteria: right-handedness (on standardized tests), absence of left handers in the family, left hemisphere integrity. Group 1 comprises cases that are unreliable because the handedness data are missing and/or because left hemisphere lesions were known to be present or probably were so. Group 2 comprises cases with full clinical data but no formal test of handedness, with familial cases of left-handedness and/or without satisfactory evidence of left hemisphere integrity. Groups 3 comprises the 26 reliable cases, that is those with proven right-handedness, no left-handers in the family and with proven hemisphere integrity. We discuss the implications of these cases. PMID- 2193903 TI - Cranial and spinal tumors with meningitic onset. AB - We review the literature on cases of cranial or spinal tumor presenting with meningitic symptoms. Embryonal tumors-dermoid cysts, epidermoid cysts, craniopharyngiomas, teratomas-and malignant gliomas were the cause of most of the episodes of chemical meningitis, single or multiple in patients with no neurological symptoms. Differential diagnosis from aseptic meningitis, especially from Mollaret aseptic meningitis, is essential. PMID- 2193904 TI - Clinicostatistical study of lower lip mucoceles. AB - We reviewed 70 patients with lower lip mucoceles for patient characteristics, clinical features, and histopathologic findings. These cases represented approximately 75% of oral mucoceles seen in the Department of Otolaryngology, Takeda General Hospital, between February 1985 and July 1988. Patients were divided almost equally between males and females, with ages ranging from 2 to 63 years, with the highest incidence of lesions occurring in the second decade. Duration of the lesions varied greatly from a few days to 3 years, with no correlation to size. The most commonly affected site was opposite the upper lateral incisor, with the incidence divided almost equally between right and left side. Of 70 biopsies, 68 were mucous extravasation cysts and 2 were mucous retention cysts. Surgical excision was the treatment of choice, with recurrence of the lesion in only 2 cases. PMID- 2193905 TI - Blindness following bilateral radical neck dissection. AB - Blindness after bilateral radical neck dissection is a rare complication. A recent patient, who suffered total blindness after simultaneous bilateral radical neck dissection, is the fifth case reported. It is, however, the first with pathological study of the optic tracts. Detailed microscopic examination revealed bilateral intraorbital hemorrhagic optic nerve infarction without evidence of embolization or ophthalmic artery occlusion. The probable etiology of this event is an episode of prolonged hypotension. An additional etiologic factor may be increased resistance to blood flow caused by venous hypertension, resulting from bilateral internal jugular vein ligation. PMID- 2193906 TI - Extramedullary plasmacytoma of the parotid. AB - Primary extramedullary plasmacytoma (PEMP) is a tumor of atypical neoplastic cells that arise outside the bone marrow in patients without clinical evidence of existing multiple myeloma. These rare tumors, which can occur in virtually any part of the body, have shown a clear predilection for the head and neck. Yet despite the fact that nearly 80% of these tumors can be found in the upper respiratory tract or oral cavity, their involvement in the parotid is singularly rare. The clinical behavior of this tumor is not yet well-defined, and local recurrence, distant metastasis, and transformation to multiple myeloma have all been reported. Since the first case of parotid PEMP was reported in 1965, 8 additional cases have been noted in the literature. This is the 9th case of PEMP of the parotid to be described. PMID- 2193907 TI - Glucoregulation and hormonal responses to maximal exercise in non-insulin dependent diabetes. AB - Maximal dynamic exercise results in a postexercise hyperglycemia in healthy young subjects. We investigated the influence of maximal exercise on glucoregulation in non-insulin-dependent diabetic subjects (NIDDM). Seven NIDDM and seven healthy control males bicycled 7 min at 60% of their maximal O2 consumption (VO2max), 3 min at 100% VO2max, and 2 min at 110% VO2max. In both groups, glucose production (Ra) increased more with exercise than did glucose uptake (Rd) and, accordingly, plasma glucose increased. However, in NIDDM subjects the increase in Ra was hastened and Rd inhibited compared with controls, so the increase in glucose occurred earlier and was greater [147 +/- 21 to 169 +/- 19 (30 min postexercise) vs. 90 +/- 4 to 100 +/- 5 (SE) mg/dl (10 min postexercise), P less than 0.05]. Glucose levels remained elevated for greater than 60 min postexercise in both groups. Glucose clearance increased during exercise but decreased postexercise to or below (NIDDM, P less than 0.05) basal levels, despite increased insulin levels (P less than 0.05). Plasma epinephrine and glucagon responses to exercise were higher in NIDDM than in control subjects (P less than 0.05). By use of the insulin clamp technique at 40 microU.m-2.min-1 of insulin with plasma glucose maintained at basal levels, glucose disposal in NIDDM subjects, but not in controls, was enhanced 24 h after exercise. It is concluded that, because of exaggerated counter-regulatory hormonal responses, maximal dynamic exercise results in a 60-min period of postexercise hyperglycemia and hyperinsulinemia in NIDDM. However, this event is followed by a period of increased insulin effect on Rd that is present 24 h after exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2193908 TI - Effects of tidal volume and methacholine on low-frequency total respiratory impedance in dogs. AB - The frequency dependence of respiratory impedance (Zrs) from 0.125 to 4 Hz (Hantos et al., J. Appl. Physiol. 60: 123-132, 1986) may reflect inhomogeneous parallel time constants or the inherent viscoelastic properties of the respiratory tissues. However, studies on the lung alone or chest wall alone indicate that their impedance features are also dependent on the tidal volumes (VT) of the forced oscillations. The goals of this study were 1) to identify how total Zrs at lower frequencies measured with random noise (RN) compared with that measure with larger VT, 2) to identify how Zrs measured with RN is affected by bronchoconstriction, and 3) to identify the impact of using linear models for analyzing such data. We measured Zrs in six healthy dogs by use of a RN technique from 0.125 to 4 Hz or with a ventilator from 0.125 to 0.75 Hz with VT from 50 to 250 ml. Then methacholine was administered and the RN was repeated. Two linear models were fit to each separate set of data. Both models assume uniform airways leading to viscoelastic tissues. For healthy dogs, the respiratory resistance (Rrs) decreased with frequency, with most of the decrease occurring from 0.125 to 0.375 Hz. Significant VT dependence of Rrs was seen only at these lower frequencies, with Rrs higher as VT decreased. The respiratory compliance (Crs) was dependent on VT in a similar fashion at all frequencies, with Crs decreasing as VT decreased. Both linear models fit the data well at all VT, but the viscoelastic parameters of each model were very sensitive to VT. After methacholine, the minimum Rrs increased as did the total drop with frequency. Nevertheless the same models fit the data well, and both the airways and tissue parameters were altered after methacholine. We conclude that inferences based only on low-frequency Zrs data are problematic because of the effects of VT on such data (and subsequent linear modeling of it) and the apparent inability of such data to differentiate parallel inhomogeneities from normal viscoelastic properties of the respiratory tissues. PMID- 2193909 TI - Direct positive inotropic and vasoconstrictor effects of endothelin. AB - Endothelin, a newly discovered vasoconstrictor peptide, when added to isolated cat papillary muscles, induced a direct positive inotropic effect that was slow in onset but of long duration. The magnitude of the developed force was concentration dependent. Endothelin exerted a marked concentration-dependent vasoconstriction in isolated cat carotid arteries and rabbit aortic rings. In both the carotid arteries and the aortic rings, endothelin induced a similar vasoconstrictor effect in the presence or absence of an intact endothelium. Addition of propyl gallate, a 5-lipoxygenase inhibitor, ibuprofen, a cyclooxygenase inhibitor, or SKF-525A, a cytochrome P450 inhibitor, at 2 microM did not significantly attenuate the ability of endothelin to vasoconstrict aortic rings in the presence or absence of an intact endothelium. These results demonstrate that the vasoconstrictor activity of endothelin operates independently of all three pathways of arachidonic acid metabolism (i.e., lipoxygenase, cyclooxygenase, or cytochrome P450 pathways) and is not dependent upon other endothelium-derived mediators (e.g., endothelium-derived relaxing factor, or eicosanoids) in these preparations. Moreover, endothelin exerts a direct positive inotropic effect in isolated cat ventricular myocardial tissue. PMID- 2193910 TI - A mutation of the transactivation gene of satellite bacteriophage P4 that suppresses the rpoA109 mutation of Escherichia coli. AB - Satellite bacteriophage P4 requires the products of the late genes of a helper such as P2 in order to grow lytically. The Escherichia coli rpoA109 mutation, which alters the alpha subunit of RNA polymerase, prevents transcription of the late genes of bacteriophage P2. Suppressor mutations that define the P2 ogr gene overcome this block. We found that P4 lytic growth using a P2 ogr+ prophage helper was prevented by the rpoA109 mutation but that this block was overcome when the P2 helper carried the suppressor mutation in the ogr gene. Furthermore, we isolated and characterized four independent mutations in P4, called org, that suppress the E. coli rpoA109 mutation by allowing P4 lytic growth using a P2 ogr+ helper. DNA sequence analysis revealed that the four independent org mutations are identical and that they occur in the P4 delta gene, which codes for a factor that positively regulates the transcription of the P2 and P4 late genes. delta is predicted to code for a basic 166-amino-acid residue protein. Each 83-residue half of the predicted delta gene product is similar to the predicted 72-residue proteins encoded by the ogr gene of P2 and the B gene of phage 186. PMID- 2193911 TI - Bacteriophage P2 ogr and P4 delta genes act independently and are essential for P4 multiplication. AB - Satellite bacteriophage P4 requires the products of the late genes of a helper phage such as P2 for lytic growth. Expression of the P2 late genes is positively regulated by the P2 ogr gene in a process requiring P2 DNA replication. Transactivation of P2 late gene expression by P4 requires the P4 delta gene product and works even in the absence of P2 DNA replication. We have made null mutants of the P2 ogr and P4 delta genes. In the absence of the P4 delta gene product, P4 multiplication required both the P2 ogr protein and P2 DNA replication. In the absence of the P2 ogr gene product, P4 multiplication required the P4 delta protein. In complementation experiments, we found that the P2 ogr protein was made in the absence of P2 DNA replication but could not function unless P2 DNA replicated. We produced P4 delta protein from a plasmid and found that it complemented the null P4 delta and P2 ogr mutants. PMID- 2193912 TI - Characterization of ompF domains involved in Escherichia coli K-12 sensitivity to colicins A and N. AB - Various ompF-ompC, ompC-ompF, and ompF-ompC-ompF chimeric genes were used to locate the domains of the OmpF protein involved in cellular sensitivity to colicins. Various parts of the porin participate in the entry of colicins. Colicin N receptor activity was found to require three regions: RN1, located between residues 1 and 63; RN2, located between residues 115 and 262; and RN3, located between residues 279 and 297. The central domain from residues 143 to 262 is involved during the translocation step after the binding step. A large region, including residues 1 to 262, is necessary during colicin A entry. The locations and interactions between these domains specifically required for the uptake of colicins to occur are described and discussed with regard to the homology and topology of the OmpC, OmpF, and PhoE porins. PMID- 2193913 TI - Oxidation of aromatic alcohols by purified methanol dehydrogenase from Methylosinus trichosporium. AB - Methanol dehydrogenase was found to be present in subcellular preparations of methanol-grown Methylosinus trichosporium and occurred almost wholly in the soluble fraction of the cell. The enzyme, purified by DEAE-Sephadex and Sephadex G-100 chromatography, showed broad specificity toward different substrates and oxidized the aromatic alcohols benzyl, vanillyl, and veratryl alcohols in addition to a range of aliphatic primary alcohols. No enzyme activity was found toward the corresponding aldehydes of the alcohols tested. The Km for methanol was 50 microM, and that for the aromatic alcohols was in the range of 1 to 2 mM. EDTA and p-nitrophenylhydrazine, which are inhibitors of methanol oxidation in whole cells of methylotrophs, had little effect on activity of the purified enzyme. The results now extend the range of substrates oxidized by methanol dehydrogenase to include the aromatic alcohols. PMID- 2193914 TI - Mutations leading to constitutive expression from the TOL plasmid meta-cleavage pathway operon are located at the C-terminal end of the positive regulator protein XylS. AB - The XylS protein is the positive activator of the TOL plasmid meta-cleavage pathway operon for the metabolism of alkylbenzoates in Pseudomonas putida. The regulator stimulates transcription from the TOL meta pathway operon promoter (Pm) when activated by benzoate effectors or in the absence of effectors when overproduced. xylS mutant alleles that encode regulators which constitutively mediate expression from Pm were isolated and characterized. The mutant proteins all exhibit single amino acid substitutions adjacent to putative alpha-helix-turn alpha-helix domains at their C-terminal ends. The XylS mutant proteins can still be partially activated by the usual and unusual benzoate effectors for the wild type regulator and when activated stimulate higher levels of transcription from Pm. PMID- 2193915 TI - Translocation and compartmentalization of Escherichia coli hemolysin (HlyA). AB - Hemolysin plasmids were constructed with mutations in hlyB, hlyD, or both transport genes. The localization of hemolysin activity and HlyA protein in these mutants was analyzed by biochemical and immunological methods. It was found that mutants defective in hlyB accumulated internal hemolysin, part of which was associated with the inner membrane and was degraded in the late logarithmic growth phase. In an HlyB+ HlyD- mutant, hemolysin was predominantly localized in the membrane compartment. Labeling of these Escherichia coli cells with anti-HlyA antibody indicated that part of HlyA, presumably the C-terminal end but not the pore-forming domains, was already transported to the cellular surface. This finding suggests that HlyB is able to recognize the C-terminal signal of the HlyA protein and to initiate its translocation across the membranes. PMID- 2193916 TI - Cloning of spiramycin biosynthetic genes and their use in constructing Streptomyces ambofaciens mutants defective in spiramycin biosynthesis. AB - Several cosmid clones from Streptomyces ambofaciens containing the spiramycin resistance gene srmB were introduced into S. fradiae PM73, a mutant defective in tylosin synthesis, resulting in tylosin synthesis. The DNA responsible for this complementation was localized to a 10.5-kilobase EcoRI fragment. A 32-kilobase DNA segment which included the srmB spiramycin resistance gene and DNA which complemented the defect in strain PM73 were mutagenized in vivo with Tn10 carrying the gene for Nmr (which is expressed in Streptomyces spp.) or in vitro by insertional mutagenesis with a drug resistance gene (Nmr) cassette. When these mutagenized DNA segments were crossed into the S. ambofaciens chromosome, three mutant classes blocked in spiramycin synthesis were obtained. One mutant accumulated two precursors of spiramycin, platenolide I and platenolide II. Two mutants, when cofermented with the platenolide-accumulating mutant, produced spiramycin. Tylactone supplementation of these two mutants resulted in the synthesis of a group of compounds exhibiting antibiotic activity. Two other mutants failed to coferment with any of the other mutants or to respond to tylactone supplementation. PMID- 2193917 TI - Genetic suppression demonstrates interaction of TonB protein with outer membrane transport proteins in Escherichia coli. AB - Energy-coupled reactions of the Escherichia coli outer membrane transport proteins BtuB and Cir require the tonB product. Some point mutations in a region of btuB and cir that is highly conserved in TonB-dependent transport proteins led to loss of TonB-coupled uptake of vitamin B12 and colicin Ia, whereas binding was unaffected. Most other point mutations in this region had no detectable effect on transport activity. Mutations in tonB that suppressed the transport defect phenotype of these btuB mutations were isolated. All carried changes of glutamine 165 to leucine, lysine, or proline. The various tonB mutations differed markedly in their suppression activities on different btuB or cir mutations. This allele specificity of suppression indicates that TonB interacts directly with the outer membrane transport proteins in a manner that recognizes the local conformation but not specific side chains within this conserved region. An effect of the context of the remainder of the protein was seen, since the same substitution (valine 10----glycine) in btuB and cir responded differently to the suppressors. This finding supports the proposal that TonB interacts with more of the transport proteins than the first conserved domain alone. PMID- 2193918 TI - DNA sequence of a Fibrobacter succinogenes mixed-linkage beta-glucanase (1,3-1,4 beta-D-glucan 4-glucanohydrolase) gene. AB - The DNA sequence of a mixed-linkage beta-glucanase (1,3-1,4-beta-D-glucan 4 glucanohydrolase [EC 3.2.1.73]) gene from Fibrobacter succinogenes cloned in Escherichia coli was determined. The general features of this gene are very similar to the consensus features for other gram-negative bacterial genes. The gene product was processed for export in E. coli. There is a high level of sequence homology between the structure of this glucanase and the structure of a mixed-linkage beta-glucanase from Bacillus subtilis. The nonhomologous region of the amino acid sequence includes a serine-rich region containing five repeats of the sequence Pro-Xxx-Ser-Ser-Ser-Ser-(Ala or Val) which may be functionally related to the serine-rich region observed in Pseudomonas fluorescens cellulase and the serine- and/or threonine-rich regions observed in Cellulomonas fimi endoglucanase and exoglucanase, in Clostridium thermocellum endoglucanases A and B, and in Trichoderma reesei cellobiohydrolase I, cellobiohydrolase II, and endoglucanase I. PMID- 2193919 TI - Cloning, sequence, and expression of the pantothenate permease (panF) gene of Escherichia coli. AB - Pantothenate permease, the product of the panF gene, catalyzes the sodium dependent uptake of extracellular pantothenate. The panF gene was isolated from an Escherichia coli genomic DNA library and subcloned into multicopy plasmids. Increased copy number of the panF+ allele resulted in increased rates of pantothenate uptake and a significant increase in the steady-state intracellular pantothenate concentration. Despite the higher levels of pantothenate, the utilization of pantothenate for coenzyme A formation was not elevated, indicating that pantothenate kinase activity is the dominant regulator of coenzyme A biosynthesis. DNA sequencing of the panF gene revealed the presence of a single open reading frame that encoded a hydrophobic protein with a molecular weight of 51,992. Sequence analysis predicts that pantothenate permease is an integral membrane protein possessing 12 hydrophobic membrane-spanning domains connected by short hydrophilic sequences. The predicted topological profile of pantothenate permease is similar to that of other membrane carriers that catalyze cation dependent symport. PMID- 2193920 TI - Replication of the broad-host-range plasmid RK2: direct measurement of intracellular concentrations of the essential TrfA replication proteins and their effect on plasmid copy number. AB - The trfA gene of the broad-host-range plasmid RK2 is essential for initiation of plasmid replication. Two related TrfA proteins of 43 and 32 kilodaltons (kDa) are produced by independent translation initiation at two start codons within the trfA open reading frame. These proteins were o overproduced in Escherichia coli and partially purified. Rabbit antisera raised against the 32-kDa TrfA protein (TrfA-32) and cross-reacting with the 43-kDa protein (TrfA-43) were used in Western blotting (immunoblotting) assays to measure intracellular TrfA levels. In logarithmically growing E. coli HB101, RK2 produced 4.6 +/- 0.6 ng of TrfA-32 and 1.8 +/- 0.2 ng of TrfA-43 per unit of optical density at 600 nm (mean +/- standard deviation). On the basis of determinations of the number of cells per unit of optical density at 600 nm, this corresponds to about 220 molecules of TrfA-32 and 80 molecules of TrfA-43 per cell. Dot blot hybridizations showed that plasmid RK2 is present in about 15 copies per E. coli cell under these conditions. Using plasmid constructs that produce different levels of TrfA proteins, the effect of excess TrfA on RK2 replication was tested. A two- to threefold excess of total TrfA increased the copy number of RK2 by about 30%. Additional increases in TrfA protein concentration had no further effect on copy number, even at levels 170-fold above normal. An RK2 minimal origin plasmid showed a similar response to intracellular TrfA concentration. These results demonstrate that TrfA protein concentration is not strictly rate limiting for RK2 replication and that a mechanism that is independent of TrfA concentration functions to limit RK2 copy number in the presence of excess TrfA. PMID- 2193921 TI - Mutations in the trfA replication gene of the broad-host-range plasmid RK2 result in elevated plasmid copy numbers. AB - Mutated forms of trfA, the replication protein gene of plasmid RK2, that support a minimal RK2 origin plasmid in Escherichia coli at copy numbers up to 23-fold higher than normal have been isolated. Six such high-copy-number (copy-up) mutations were mapped and sequenced. In each case, a single base transition led to an amino acid substitution in the TrfA protein primary sequence. The six mutations affected different residues of the protein and were located within a 69 base-pair region encoding 24 amino acids. Dominance tests showed that each of the mutants can be suppressed by wild-type trfA in trans, but suppression is highly dependent on the amount of wild-type protein produced. Excess mutant TrfA protein provided in trans significantly increased the copy number of RK2 and other self replicating derivatives of RK2 that contain a wild-type trfA gene. These observations suggest that the mutations affect a regulatory activity of the TrfA replication protein that is a key factor in the control of initiation of RK2 replication. PMID- 2193922 TI - DNA sequence analysis of pglA and mechanism of export of its polygalacturonase product from Pseudomonas solanacearum. AB - The pglA gene encodes a 52-kilodalton extracellular polygalacturonase (PGA) which is associated with the phytopathogenic virulence of Pseudomonas solanacearum. The nucleotide sequence of pglA and the putative amino acid sequence of the PGA protein were determined. A computer search identified a 150-residue region of PGA which was similar (41%) to the amino acid sequence of a region of the PG-2A polygalacturonase from tomato. Comparison of the amino terminus of the pglA open reading frame with the actual amino-terminal sequence of purified extracellular PGA suggested that pglA is initially translated as a higher-molecular-mass precursor with a 21-residue amino-terminal signal sequence. Localization of various pglA-phoA fusion proteins in Escherichia coli and P. solanacearum indicated that the 21-residue leader sequence directs the export of PhoA only as far as the periplasm of both bacteria. Deletion of the last 13 residues of PGA eliminated its catalytic activity, as well as its ability to be exported outside of the P. solanacearum cell. Our results suggest that PGA excretion occurs in two steps. The first step involves a signal sequence cleavage mechanism similar to that used for periplasmic proteins and results in export of PGA across the inner membrane; the second step (transit of the outer membrane) occurs by an unknown mechanism requiring sequences from the mature PGA protein and biochemical factors absent from E. coli. PMID- 2193923 TI - Rhizobium meliloti and Rhizobium leguminosarum dctD gene products bind to tandem sites in an activation sequence located upstream of sigma 54-dependent dctA promoters. AB - Free-living rhizobia transport external C4-dicarboxylates to use as sole carbon sources, and uptake of these compounds is essential for nitrogen fixation by rhizobial bacteroids. In both Rhizobium leguminosarum and Rhizobium meliloti, the genes dctB and dctD are believed to form an ntrB/ntrC-like two-component system which regulates the synthesis of a C4-dicarboxylate transport protein encoded by dctA. Here we confirm the identity of sigma 54-dependent promoters previously hypothesized for the R. leguminosarum and R. meliloti dctA genes and demonstrate that repeated, partial dyad symmetry elements located about 75 base pairs upstream of each promoter are essential for fully regulated transcription. Furthermore, we show that both repeats bound dctD protein and that together they resulted in succinate-sensitive transcription when placed upstream of another sigma 54 consensus promoter, that of R. meliloti nifH. PMID- 2193924 TI - Molecular cloning and characterization of an extracellular protease gene from Aeromonas hydrophila. AB - A structural gene which codes for an extracellular protease in Aeromonas hydrophilia SO2/2 and D13 was cloned in Escherichia coli C600-1 by using pBR322 as a vector. The gene codes for a temperature-stable protease with a molecular mass of approximately 38,000 daltons. The protein was secreted to the periplasm of E. coli C600-1 and purified by osmotic shock. Cloned protease (P3) was identical in molecular mass and properties to the one purified from A. hydrophila SO2/2 culture supernatant as an extracellular product. PMID- 2193925 TI - Ethanol formation in adh0 mutants reveals the existence of a novel acetaldehyde reducing activity in Saccharomyces cerevisiae. AB - A strain of Saccharomyces cerevisiae has been constructed which is deficient in the four alcohol dehydrogenase (ADH) isozymes known at present. This strain (adh0), being irreversibly mutated in the genes ADH1, ADH3, and ADH4 and carrying a point mutation in the gene ADH2 coding for the glucose-repressible isozyme ADHII, still produces up to one third of the theoretical maximum yield of ethanol in a homofermentative conversion of glucose to ethanol. Analysis of the glucose metabolism of adh0 cells shows that the lack of all known ADH isozymes results in the formation of glycerol as a major fermentation product, accompanied by a significant production of acetaldehyde and acetate. Treatment of glucose-growing adh0 cells with the respiratory-chain inhibitor antimycin A leads to an immediate cessation of ethanol production, demonstrating that ethanol production in adh0 cells is dependent on mitochondrial electron transport. Reduction of acetaldehyde to ethanol in isolated mitochondria could also be demonstrated. This reduction is apparently linked to the oxidation of acetaldehyde to acetate. Preliminary data suggest that this novel type of ethanol formation in S. cerevisiae is associated with the inner mitochondrial membrane. PMID- 2193926 TI - Co-overproduction and localization of the Escherichia coli motility proteins motA and motB. AB - The motility genes motA and motB of Escherichia coli were placed under control of the Serratia marcescens trp promoter. After induction with beta-indoleacrylic acid, the levels of MotA and MotB rose over about a 3-h period, reaching plateau levels approximately 50-fold higher than wild-type levels. Both overproduced proteins inserted into the cytoplasmic membrane. Growth and motility were essentially normal, suggesting that although the motor is a proton-conducting device, MotA and MotB together do not constitute a major proton leak. Derivative plasmids which maintained an intact version of motB but had the motA coding region deleted in various ways were constructed. With these, the levels of MotB were much lower, reaching a peak within 30 min after induction and declining thereafter; pulse-chase measurements indicated that a contributing factor was MotB degradation. The low levels of MotB occurred even with an in-frame internal deletion of motA, whose translational initiation and termination sites were intact, suggesting that it is the MotA protein, rather than the process of MotA synthesis, that is important for MotB stability. Termination at the usual site of overlap with the start of motB (ATGA) was not an absolute requirement for MotB synthesis but did result in higher rates of synthesis than when translation of motA information terminated prematurely. Even in the total absence of MotA, the MotB that was synthesized was found exclusively in the cytoplasmic membrane fraction. In wild-type cells, MotA was estimated by immunoprecipitation to be in about fourfold excess over MotB; a previous estimate of 600 +/- 250 copies of MotA per cell then yielded an estimate of 150 +/- 70 copies of MotB per cell. PMID- 2193927 TI - Prey-derived signals regulating duration of the developmental growth phase of Bdellovibrio bacteriovorus. AB - The filamentous elongation typical of growth-phase cells of the predatory bacterium Bdellovibrio bacteriovorus is mediated by regulatory signals that are derived from the prey cell itself. These signals regulate the differentiation of growth-phase cells into the attack phase and appear to be required for continued filamentous growth by prey-dependent wild-type bdellovibrios and their prey independent mutant derivatives alike. Using a prey-independent bdellovibrio strain, we have developed an assay for the detection and quantification of the growth-extending signal activity present in extracts of prey cells. This prey derived regulatory activity was shown to be independent of its nutritional contribution to the bdellovibrios and was found to occur in heat-stable, proteinlike compounds of a variety of native molecular weights within the soluble fraction of extracts from both gram-negative and gram-positive bacteria. PMID- 2193929 TI - Regulation of Escherichia coli sigma F RNA polymerase by flhD and flhC flagellar regulatory genes. AB - The sigma F RNA polymerase has been characterized biochemically and is known to transcribe several flagellar genes in Escherichia coli. It was found that while the flagellar regulatory genes flhD and flhC are required for sigma F activity, the sizes of their corresponding gene products are inconsistent with their encoding sigma F itself. PMID- 2193928 TI - Molecular characterization of an Enterobacter cloacae gene (romA) which pleiotropically inhibits the expression of Escherichia coli outer membrane proteins. AB - The introduction of a newly cloned Enterobacter cloacae chromosomal gene romA, into Escherichia coli and E. cloacae resulted in enhancement of resistance to quinolones, beta-lactams, chloramphenicol, and tetracycline. The primary effect of romA on a multicopy vector in E. coli was almost complete inhibition of OmpF expression in the outer membrane. From the experiments with ompR and envZ mutants or with ompF-lacZ and ompC-lacZ fusion plasmids, it was concluded that this inhibition is posttranscriptional. The introduction of romA on a multicopy vector into strains with micF deletion elicited only a moderate decrease in OmpF protein expression. This indicates that reduction of OmpF expression by romA is partly mediated posttranscriptionally by the activation of micF. Moreover, the overexpression of RomA protein from an isopropyl-beta-D-thiogalactopyranoside (IPTG)-inducible promoter resulted in nearly complete inhibition of expression of OmpC and OmpA, as well as OmpF. Taken together with an observation in a recent study that overexpressed OmpC inhibited the synthesis of OmpA and LamB, a possible inhibitory mechanism at the translational stage of the synthesis of outer membrane proteins should also be considered. By Southern hybridization, romA was generally detected in the chromosomes of all E. cloacae strains tested but not in the E. coli K-12 chromosome. Sequence data show that there is an open reading frame specifying 368 amino acids residues including a putative signal peptide. RomA appears to belong to the outer membrane protein family since it was extractable from an outer membrane preparation, but no sequence homology to other outer membrane proteins was detected. PMID- 2193930 TI - Primary structure of a fucose-specific lectin obtained from a mushroom, Aleuria aurantia. AB - Aleuria aurantia lectin (AAL) is a protein composed of two identical subunits having no carbohydrate chain and shows sugar-binding specificity for L-fucose. Full-length cDNA encoding for the lectin has been isolated from a lambda gt11 library, screened with an antiserum directed against AAL. The cDNA clone contained 1,370 nucleotides and an open reading frame of 939 nucleotides encoding 313 amino acids. The amino-terminal sequence (residues 1-30) of the lectin isolated from the mushroom coincided with the deduced amino acid sequence starting from proline at the 2nd residue, indicating that the mature AAL consists of 312 amino acids. Its molecular weight is calculated to be 33,398. The deduced amino acid sequence shows that AAL includes six internal homologous regions, and has considerable homology with a hemagglutinin from a Gram-negative bacterium, Myxococcus xanthus, which forms a fruiting body. No significant homology was observed with higher plant or animal lectins. The recombinant AAL produced by Escherichia coli JM109 carrying the AAL expression plasmid pKA-1 [Fukumori, F. et al. (1989) FEBS Lett. 250, 153-156] was purified from the cell lysate by affinity chromatography using a fucose-starch column, and hundreds of milligrams of the lectin was obtained. The recombinant lectin showed the same biochemical characteristics and sugar binding specificity as did the natural AAL. PMID- 2193931 TI - Lysosomal glycogen accumulation in rat liver and its in vivo kinetics after a single intraperitoneal injection of acarbose, an alpha-glucosidase inhibitor. AB - A single intraperitoneal injection of acarbose (400 mg/kg) into rats caused lysosomal accumulation of glycogen in the liver, mimicking the cytological characteristics of human glycogen storage disease type II (Pompe's disease). The animal model is therefore useful for studying the pathogenesis of the disease. In the present study, we applied this model to examine the lysosomal hydrolytic pathway of glycogen in vivo. To quantify the lysosomal glycogen, the lysosome rich fraction was rapidly prepared from liver homogenate by agglutination in the presence of Ca2+. Then the fraction was treated with alpha-amylase in isotonic medium to remove cytosolic glycogen, followed by transfer to hypotonic conditions in the presence of Triton X-100 to destroy total glycogen. The amount of lysosomal glycogen was calculated from the difference between the glycogen levels measured before and after the treatment under hypotonic conditions, and then it was corrected based on measurements of the intactness (%) of lysosomes and the recovery (%) of the lysosomal marker enzyme (beta NAGase). We observed no measurable lysosomal glycogen in normal liver by this method, and this was confirmed by electron microscopy. After administration of acarbose, the lysosomal glycogen level increased to 2.5 mg/g liver within 2 days, and then decreased gradually at a rate of 0.4 mg/day/g. The accumulation of glycogen in the lysosomes at an initial velocity of 1.5 mg/day/g liver may be considered as the amount of glycogen that would normally be degraded by acid alpha-glucosidase. Therefore, assuming that the liver breaks down about 40 mg glycogen/day/g, we estimated that about 3% of the glycogen would be hydrolyzed by the lysosomal pathway. PMID- 2193932 TI - Cloning and nucleotide sequences of livB and livC, the structural genes encoding binding proteins of the high-affinity branched-chain amino acid transport in Salmonella typhimurium. AB - The liv gene cluster responsible for encoding the high-affinity branched-chain amino acid transport proteins in Salmonella typhimurium was mapped in the 7.6 kilobase HindIII-SacI segment of plasmid pMN12 by utilizing the gene dosage effect. By subcloning and biochemical analysis, the livB and livC structural genes encoding the leucine-, isoleucine-, valine-, threonine-binding protein (LIVT-BP) and the leucine-specific binding protein (L-BP), respectively, were localized within the 3,617-base HindIII-BstEII segment. Upon determining the nucleotide sequence of the 3,617 bases, we found that the coding sequence of the livB gene (1,095 base pairs) starts at the position 355 and specifies the precursor LIVT-BP of 365 amino acid residues, and the livC gene (1,107 base pairs) starts at the position 2,452 and encodes the precursor L-BP of 369 amino acid residues. The two genes, separated by a 1-kilobase intergenic region, each possess potential promoters and rho-independent transcriptional terminators. The mature LIVT-BP and L-BP are produced by removing the putative 21 and 23 signal peptides from the respective precursors. In comparison with the analogous two binding proteins from Escherichia coli K-12, strong homologies are observed. PMID- 2193933 TI - Tissue reaction to subcutaneous implantation of a collagen sponge. A histological, ultrastructural, and immunological study. AB - The biocompatibility of a subcutaneously implanted bovine collagen sponge (Haemostagen) was studied in rats by analyzing tissue reactions up to 3 months by histological and ultrastructural methods; in addition, the level of serum antibodies to bovine type I collagen (the major implant collagen) was measured by solid-phase radioimmunoassay. By 8 h after implantation, the implant was completely filled with polymorphonuclear cells (PMNs). After 8 days, fibroblasts had developed a granulation tissue within the sponge and the PMNs had almost disappeared. The small residue that remained after 1 month consisted of some densely packed collagen fibrils containing giant cells, which had disappeared by 3 months. No antibodies to bovine type I collagen were found in the sera of implanted rats. PMID- 2193934 TI - [Value of Illizarov's method in the treatment of long bone pseudarthrosis. Apropos of a A.S.A.M.I.F series of 87 cases]. AB - This study is the outcome of multicenter endeavour compiling 87 cases of pseudoarthrosis managed according to principles set forth by G.A. Ilizarov. All clinical forms are described: simple pseudoarthrosis (non-infected and without loss of substance); septic pseudoarthrosis; pseudoarthrosis with loss of bone substance, both septic and aseptic. This method is used in the majority of cases. This method is used in the majority of cases after several consecutive unavailing attempts with conventional therapeutical procedures. Considering all situations, the lesions heal in over 90% of cases and the infection subsides with an equal rate of success. Such results are achieved within a period of 5 months. Sequelae or complications imputable to the method are few. Indications are specified, which depend upon the clinical form of the treated pseudoarthrosis, as well as upon the surgeon's personal skill. PMID- 2193935 TI - [Anatomic pecularities of the inguinal canal in West Indians. Influence on the management of inguinal hernia]. AB - Inguinal and umbilical hernias are much more frequent in the black and half-breed than in the white population. We have observed anatomical differences in the inguinal region between Whites and Blacks. The latter have a vertical, wide subcutaneous ring and a smaller conjoined tendon, and it is hardly possible to reconstruct the fascia of the obliquus externus abdominis anterior to the cord in them. For Black patients, we propose the suture of the conjoined tendon to the crural arch, like in the Bassini procedure, and the suture of the fascia of the obliquus externus to the arch, but in a retrofunicular position. This technique allows, so to speak, duplicating the caudal connection of the conjoined tendon to the arch by means of the extensive suture of 2 tissues of similar nature, ie. the fascia of the obliquus externus and the crural arch. PMID- 2193936 TI - [Surgical treatment of infectious aneurysm of the popliteal artery. Description of a case caused by Campylobacter jejuni and a review of the literature]. AB - The authors describe a case of mycotic aneurysm of the popliteal artery secondary to Campylobacter jejuni-derived infectious endocarditis treated by excision and in situ femoro tibial venous bypass, and take the opportunity to review 14 literature cases of infectious aneurysm of popliteal artery. This diagnosis is most frequently evoked by the development in an infectious setting of a throbbing inflammatory mass in the popliteal fossa. Management is aimed at controlling the infection and insuring proper distal vascularization. Eradication of the infection rests with the excision of the aneurysm and adequate antibiotherapy for at least 6 weeks. Distal vascularization is best provided (2 cases) by extra anatomical bypass. However, in situ bypassing (9) is possible provided apyrexia and negative blood cultures have been obtained by preoperative antibiotherapy. The material used must be a venous autograft, whenever possible. PMID- 2193937 TI - [Degenerative mucus-producing villous tumor of the gallbladder. A case]. PMID- 2193938 TI - Clinical application of subforms of creatine kinase MM and macro creatine kinases. AB - The subforms of MM isozyme of creatine kinase (ATP:creatine N-phosphotransferase, EC 2.7.3.2, CK) in sera obtained from healthy adults and patients were determined by agarose gel isoelectric focusing (IEF). The patients were classified into six groups according to serum CK-MM activities and IEF patterns. The IEF spectra offered useful information on cell hyperplasia, augmented cell membrane permeability, cell destruction and release time of CK-MM in the circulation from the cells for diagnosis, progress observation and prognosis, especially in the cases of chronic hepatic diseases, acute myocardial infarction and muscular dystrophy. Macro CKs were also determined by IEF. Macro CKs could be completely distinguished from each other, and CK isozymes consisting of macro CK type 1 could be presumed by isoelectric points. PMID- 2193939 TI - The control of endogenous secretion of LH by gonadotrophin-releasing hormone agonists during ovarian hyperstimulation for in-vitro fertilization and embryo transfer. PMID- 2193940 TI - Transvaginal colour flow imaging of the uterine arteries during the ovarian and menstrual cycles. AB - Uterine arterial blood flow was studied at defined times during the ovarian or menstrual cycles. Transvaginal colour pulsed ultrasound was used to identify the vessels in 23 healthy women. Blood flow impedance as reflected by the pulsatility index (PI) was determined for both arteries on 132 occasions. There was no significant difference in the PI values between the right and left arteries. The average PI value was used for subsequent analysis (range 0.5-5.6; mean 2.8). Peak mean PI values occurred on day 1 of menses (4.6), the day of the plasma oestradiol peak (3.7) and the day of the LH peak plus 3 (2.9). The lowest mean PI values (indicating the least impedance to blood flow) occurred on the day of the LH peak minus 6 (2.6), and the day of the LH peak plus 9 (1.9). There are complex temporal relationships between uterine blood flow, ovarian morphology, the concentrations of plasma oestradiol and progesterone and the thickness of the endometrium. PMID- 2193941 TI - Follicular fluid renin concentration and IVF outcome. AB - Total renin protein concentration (TRC) was measured in stored follicular fluid (FF) samples from 42 women. Samples were selected according to their origin from follicles either without recovered ova ('empty', n = 38) or fertilized but with failed implantation ('failed', n = 36) or successful deliveries ('deliveries', n = 71). Ratios of number of embryos transferred to number of infants delivered were 2:1, 3:1 or 4:2 but 1:1 was not available. Non-parametric testing was applied to FF-TRC, volume and outcome. TRC was significantly higher in the delivery than the failed (P = 0.001) or empty (P = 0.002) categories. Assuming that the range of renin in failed follicles can identify the sub-population of unsuccessful follicles in the delivery category, then elevated FF-TRC was clearly associated with successful outcome. For individual women, the odds of infant delivery increased 17-fold as a function of average FF-TRC between 10,000 and 25,000 microIU/ml. For failed and delivery but not empty follicles, higher renin levels occurred in the smaller follicles, consistent with a burst of renin synthesis associated with the presence of an oocyte. The results suggest that FF TRC relates to ovum viability with ovarian hyperstimulation and may have predictive use in IVF programmes. PMID- 2193942 TI - Preimplantation genetic diagnosis: a new simple uterine washing system. AB - A new system for lavage of the uterine cavity and blastocyst recovery has been developed. The system was tested two or more times in 11 volunteer women at high genetic risk and waiting for its clinical application. Insertion into the uterine cavity was performed under continuous ultrasonic surveillance and was successfully achieved in all cases, 73% of whom reported some pains. A volume of 40 ml of warmed sterile saline solution was injected for washing of the uterine cavity and the total volume was always recovered without any sonographically visible leakage into the peritoneal cavity. No clinical infection or menstrual irregularities were observed and the only complications after the procedure were a short lasting spotting and light menstrual-like pains. The new system, owing to its efficacy, practicality and safety, is specifically indicated for preimplantation genetic diagnosis of blastocysts. PMID- 2193943 TI - AIDS: epidemiologic features. AB - At the end of October 1988, more than 75,000 adults and more than 1000 children had been reported with acquired immunodeficiency syndrome (AIDS); more than half of those diagnosed have died. Most adult cases fall into specific risk categories: homosexual and bisexual men, intravenous drug abusers, hemophiliacs and transfusion recipients, and heterosexual partners of infected persons. These categories are related to the known transmission routes of the human immunodeficiency virus (HIV). In children, the risk groups are different; most cases represent perinatal transmission of HIV. Black and Hispanic persons are disproportionately affected by AIDS in the United States and make up almost 40% of all reported cases. In 1986, AIDS was the eighth leading cause of premature death in this country, and if current trends continue, it will become the second by 1992. Although HIV infection rates in "risk group" members have been extensively studied, much less is known about infection rates in persons outside these groups. A variety of surveys are under way to monitor the spread of HIV. The epidemiologic puzzle of Kaposi's sarcoma is considered, as well as reasons for the decrease in it as a proportion of all AIDS cases. PMID- 2193944 TI - Risk of transmission of HIV to home care and health care workers. AB - There are only three known routes of transmission of the human immunodeficiency virus (HIV): (1) exposure to blood via transfusion, sharing of contaminated needles by drug abusers, occupational needle stick or blood spill, unsterile needle injections; (2) sexual transmission; (3) perinatal exposure. There is no evidence for transmission by close interpersonal nonsexual contact or insect vectors. Health care workers are at risk for HIV transmission through accidental parenteral inoculation or extensive exposure to blood on nonintact skin or mucous membranes. Fortunately, population studies indicate that this risk is low and may be further reduced by adherence to simple infection control guidelines. The accumulated information on low rates of occupational transmission of HIV makes unwarranted the treatment of patients with acquired immunodeficiency syndrome (AIDS) or HIV infection as if they were highly contagious in the health care setting. PMID- 2193945 TI - Biology of retroviruses: detection, molecular biology, and treatment of retroviral infection. AB - The general physical characteristics and replication of retroviruses are considered, along with assays for viral products. The specific agent for acquired immunodeficiency syndrome, the human immunodeficiency virus (HIV), is characterized as a lentivirus causing persistent, lifelong infection. While human immunodeficiency virus retroviruses share many of the same properties as other replication-competent viruses, genetic variability occurs among HIV isolates, and this variability may have a considerable effect on the virus' virulence, cell type specificity, viral susceptibility to antiviral compounds, clinical presentation, and disease progression. The most notable difference between HIV replication and other retroviruses is the intricate control of HIV gene expression by viral and cellular factors. Possible mechanisms by which HIV kills infected cells include the formulation of multinucleate syncytia; cytopathic components within the virions themselves; and interaction between viral envelope proteins and the CD4 molecule on the cell surface. Agents shown to inhibit viral replication at the level of the reverse transcriptase are phosphonoformate, sulfated polysaccharides, rifabutin, and nucleoside analogs, as well as purine and pyrimidine analogs. To date, only one nucleoside analog, zidovudine, has demonstrated clear clinical benefit and anti-HIV activity. PMID- 2193946 TI - HIV virology: implications for the pathogenesis of HIV infection. AB - Infection by the human immunodeficiency virus (HIV) may result in a spectrum of disease ranging from asymptomatic seropositivity to the development of profound immunodeficiency. Features of the HIV life cycle may explain aspects of the pathogenesis of HIV-induced disease. The tropism of HIV for CD4+ cells of both lymphocytic and monocytic origin is of considerable importance in bringing about immune deficiency. The variability of the HIV envelope limits the ability of host immune response to control the infection effectively. Finally, the ability of HIV to persist is latently integrated DNA in infected cells that can be reactivated by cellular signals responsible for the control of normal immune cell activation links HIV replication to normal host cell functions. This can help explain the chronic but progressive nature of the infection. PMID- 2193947 TI - Antigenic characterization of the human immunodeficiency viruses. AB - As more is learned about the human immunodeficiency viruses HIV-1 and HIV-2, increasingly sophisticated methods of acquired immunodeficiency syndrome (AIDS) treatment and prevention may be implemented. Integral to an understanding of these viruses is an analysis of both the viral antigens and the host-immune responses to these antigens, which may differ from HIV-1 to HIV-2. Because levels of both antigen and antibody vary throughout disease development, knowledge of how and why such changes occur will lend insight into viral pathogenic mechanisms and will facilitate the development of differential diagnostic tests for classifying AIDS patients and their disease states. This task becomes very complex when dealing with HIV viruses because they possess an unprecedented number of regulatory genes for members of the retrovirus family. PMID- 2193948 TI - Langerhans cells in HIV-1 infection. AB - The skin-specific immune surveillance system protects against invading microorganisms and transformed cells expressing tumor-specific neoantigens. This system includes antigen-presenting Langerhans cells, dermal and epidermal T lymphocytes, cytokine-producing keratinocytes, and draining peripheral lymph nodes. In patients infected with human immunodeficiency virus-1 (HIV-1), this surveillance system appears to be compromised, as evidenced by a reduction in the epidermal Langerhans cell population. Because human epidermal Langerhans cell express surface-bound CD4 antigens, HLA-DR antigens, and Fc-IgG receptors, all of which are involved in HIV-1 binding to, or entry into, the target cell, the reduction in Langerhans cells in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) may be a direct consequence of HIV-1 infection and subsequent injury to Langerhans cells. Detailed ultrastructural studies have confirmed moderate to severe morphologic damage in some Langerhans cells of such patients and the presence of HIV-1-like particles on Langerhans cell surface membranes and in the extracellular spaces. The biologic consequences of Langerhans cell infection by HIV-1 could be either impaired antigen presentation function of viable Langerhans cells or possible transmission of the retrovirus to the T-cell compartment in skin or lymph nodes, with subsequent depletion of CD4+ T cells via widespread syncytia formation between HIV-1 infected and noninfected cells. The facts that herpes simplex virus, specific cytokines, and ultraviolet B radiation can activate signals for HIV-1 expression and that epidermal cells can elaborate large amounts of cytokines, particularly with enhanced ultraviolet B exposure, may have important clinical implications for HIV-1-infected patients. PMID- 2193949 TI - Clinical manifestations of HIV infection, including persistent generalized lymphadenopathy and AIDS-related complex. AB - The ability to recognize disease related to the human immunodeficiency virus (HIV) and subsequent acquired immunodeficiency syndrome (AIDS) has improved in recent years with refinement of laboratory techniques. Because of this progress, several clinical conditions can now be identified as "pre-AIDS" syndromes. These include the persistent generalized lymphadenopathy syndrome, immune thrombocytopenic purpura, the wasting syndrome, and certain predominantly neurologic presentations. All are characterized by the presence of infection with HIV, symptomatic disease, and, over time, an increasing tendency to progress to "full-blown" AIDS. PMID- 2193950 TI - HIV infection in children. AB - Human immunodeficiency virus (HIV) infection in children has emerged as a major, rapidly growing public health problem. The majority of children become infected by perinatal transmission of the virus from an infected mother. The disease is frequently associated with progressive neurologic dysfunction and with opportunistic infections. The cutaneous manifestations of pediatric HIV infection include a wide variety of fungal, bacterial, and viral infections of the skin. These diseases tend to be less responsive to conventional therapies than in the healthy child. In addition, severe seborrheic dermatitis, vasculitis, and drug eruptions are sometimes signs of HIV infection. PMID- 2193951 TI - Neurologic disorders associated with HIV infections. AB - At least 60% of patients infected with the human immunodeficiency virus (HIV) develop neurologic disorders. These may be the direct result of human immunodeficiency virus (HIV) infection, opportunistic infections, neoplastic disorders, or cerebrovascular complications. Neurologic diseases associated with HIV infection include encephalopathy, aseptic meningitis, vacuolar myelopathy, peripheral neuropathy, and myopathy. The pathogenesis of these diseases is not known, but it is likely that they will differ. There is evidence that HIV is the etiologic agent of HIV-associated meningitis and subacute encephalitis, but to date there is little evidence to implicate HIV directly as the cause of vacuolar myelopathy, peripheral neuropathies, and myopathies. The results of preliminary clinical studies suggest that treatment with zidovudine (Retrovir) may cause improvement in some patients. PMID- 2193952 TI - Clinical manifestations of classical, endemic African, and epidemic AIDS associated Kaposi's sarcoma. AB - Kaposi's sarcoma, first described in 1972, is a rare, chronic neoplasm that occurs most often in elderly men of Eastern European origin. In the mid-twentieth century, more aggressive forms of Kaposi's sarcoma were found to be an endemic disease especially common among young black men in central Africa. Kaposi's sarcoma also occurs in iatrogenically immunosuppressed patients, such as kidney transplant recipients. In 1981, the sudden occurrence of an unusual, disseminated form of Kaposi's sarcoma in homosexual men in New York and California heralded the epidemic now known as the acquired immunodeficiency syndrome (AIDS). Ninety five percent of all AIDS-associated Kaposi's sarcoma (AIDS-KS) has been in homosexual men; however, the incidence of AIDS-KS has diminished from greater than 40% of men with AIDS since 1981 to less than 20% in 1989. The remaining 5% of AIDS-KS has been seen in all other populations at risk for AIDS. The reasons for the remarkable persistent increased prevalence of AIDS-KS among homosexual men remains obscure. Clinically, AIDS-KS is a highly varied neoplastic disease characterized by multifocal mucocutaneous lesions often with lymphatic and visceral involvement. The etiology of Kaposi's sarcoma remains unknown although various hypotheses have been suggested, including endothelial-tumor growth factors, oncogenic expression, genetic predisposition, and environmental cofactors. An as-yet unidentified viruslike agent has been proposed as a possible direct cause of this neoplasm. Different treatment modalities for Kaposi's sarcoma have been employed with varying success, these include localized radiation therapy, cryotherapy, electrocauterization, surgical excision, and a variety of systemic chemotherapeutic regimens, as well as alpha-interferon. Although all available treatments help control the lesions, none lengthens survival. PMID- 2193953 TI - The changing incidence of Kaposi's sarcoma among patients with AIDS. AB - Kaposi's sarcoma (KS), the most common cancer in patients with acquired immunodeficiency syndrome (AIDS), occurs predominantly in homosexual men. However, the percentage of homosexual AIDS patients with KS has declined during the past 6 years. This and other findings suggest that one or more cofactors associated with the homosexual lifestyle, rather than a special viral strain, probably influence the development of KS in patients infected with the human immunodeficiency virus (HIV). Possible reasons for the decline include changes in homosexual behaviors, leading to the practice of safer sexual techniques, and a decrease in use of nitrite inhalants. Identification of the KS-AIDS cofactor(s) could be invaluable to developing prevention and treatment strategies. PMID- 2193954 TI - Lymphoma and other HIV-associated malignancies. AB - The immunodeficient state that evolves in persons infected with the human immunodeficiency virus (HIV) appears to increase their risk of certain types of cancer. Among these are primary lymphoma of the central nervous system, undifferentiated non-Hodgkin's lymphoma, squamous cell carcinoma, anorectal carcinoma, and cutaneous malignancies. These malignancies are similar in incidence to those seen in other immunodeficient patients. Lymphoma, in particular, is associated with a more aggressive disease state. In HIV-infected patients, the disease is usually diagnosed at a more advanced stage, frequently has extranodal involvement, and usually responds poorly to chemotherapy. Viruses, such as Epstein-Barr virus and papillomavirus, have been implicated in the pathogenesis of lymphoma and other malignancies in immunosuppressed patients, including those with HIV infection. PMID- 2193955 TI - Cutaneous manifestations of HIV infection other than Kaposi's sarcoma: clinical and histologic aspects. AB - The skin is commonly affected in patients with human immunodeficiency virus (HIV) infection. Viral, bacterial, fungal, and protozoal infections and ectoparasitic infestations may affect the skin primarily or secondarily in this patient population. In addition, common inflammatory dermatoses may be severe and persistent. Furthermore, unusual inflammatory conditions not commonly seen in immunocompetent patients may occur. The more common opportunistic infectious diseases, as well as some of the inflammatory dermatoses, in patients with HIV infection are discussed. By recognizing these conditions, patients with HIV infection can be more readily identified and treated. PMID- 2193956 TI - Antiviral therapy against HIV infection. AB - The replication of human immunodeficiency virus (HIV) can be suppressed in vivo by drugs chosen on the basis of their selective in vitro antiviral activity. Such suppression can confer prolonged survival and improved quality of life in patients with already established HIV infection. The clinical benefits indicate that targeted therapy for acquired immunodeficiency syndrome based on the emerging knowledge of replicative cycle of HIV is an attainable goal. PMID- 2193957 TI - The politics and economics of AIDS. PMID- 2193958 TI - Cosmetic leg veins: evaluation using duplex venous imaging. AB - The records of 305 consecutive patients who had presented with cosmetic symptoms related to varicose and/or spider veins over a 12-month period were studied. Following clinical assessment, 250 (82%) patients were referred for duplex venous imaging. A total of 500 lower limbs were evaluated; 236 (47%) were documented to have incompetence in the superficial venous system (long or short saphenous veins). Only 6 (1%) limbs had deep venous incompetence and 45 (9%) limbs were found to have perforator incompetence. Short saphenous vein incompetence was found in 59 (12%) limbs. In the long saphenous vein there was a consistent pattern of an increasing incidence of incompetence from the saphenofemoral junction down to the below-knee segment. The duplex imaging findings were applied to determine the optimal treatment, ie, whether surgery, sclerotherapy, or a combination of both would provide the best short- and long-term results. The possible etiology and pathophysiology of spider and varicose veins are discussed in relation to these results. PMID- 2193959 TI - A study of estrogen and progesterone receptors in spider telangiectasias of the lower extremities. AB - There is an association of some vascular tumors with estrogen receptors and an association of vascular telangiectasias with high levels of circulating estrogen. Because of this, a study of patients with lower extremity starburst telangiectasias and predisposing factors associated with hyperestrogenemic and hyperprogesteronemic states was undertaken in order to look for estrogen and progesterone receptors in biopsy specimens of lower extremity telangiectasias noted to arise in this setting. Contrary to expected results, using immunocytochemical techniques, no patient in this study was found to have estrogen or progesterone receptors present in their lower extremity telangiectasias. Possible explanations for these results are discussed. PMID- 2193960 TI - Fat transfer for aging skin: technique for rhytids. AB - Dermatologic surgeons are familiar with many surgical and nonsurgical techniques for the reduction of facial rhytids. Injectable collagen, silicone, and fibril are commonly employed as injectable filler materials. Properly done, fat transfer is another valuable tool for use in facial restoration. Fat transfer is an excellent technique for intervention in the aging process, and is easily managed as an office procedure. We will review the near-century-old history of fat grafting and outline the structural dynamics in the process of facial aging. Our experience from the last 50 fat transfer procedures performed will be reviewed with specific attention to patient selection, extraction and injection technique, complications, and overall results. PMID- 2193961 TI - The literature of dermatologic surgery and oncology: 1970-present. PMID- 2193962 TI - [The action of chemical agents at ultralow doses on biological objects]. AB - The published data on the effect of low and ultralow (up to 10(-17] doses of chemical agents on different biological systems have been reviewed. A concept of action of ultralow doses has been proposed on the basis of a notion of complex hierarchical structure of regulation in biological systems where response to strong and weak actions is carried out by different mechanisms and pathways. The times of transport of molecules of biologically active compounds to targets have been calculated on the basis of the principle of the first boundary approach by Brown's particle. Probabilistic models of mechanisms leading to complex dose dependency have been analyzed. PMID- 2193964 TI - Milestones in nursing history. PMID- 2193963 TI - Strategic planning: preparing for the twenty-first century. AB - If educational institutions for nursing are to survive these uncertain times and to experience new life in the advent of the 21st century, careful planning for the future must be undertaken. Strategic planning, a relatively new term in nursing education, is a concept designed to achieve goals in dynamic, competitive environments through the judicious allocation of resources. The primary purpose of strategic planning is to achieve success with mission while linking the institution's future to anticipated changes in the environment. Strategic planning enables an institution to function in such a manner that the acquisition of resources exceeds their depletion. The purposes of this article are to (1) provide an overview of the strategic planning process and (2) describe the strategic planning experience of one private, liberal arts college in a midwestern state. Although the case example focuses on a liberal arts college, the strategic planning process is applicable to other types of educational settings. PMID- 2193965 TI - Financial ruin or financing catastrophic health coverage: who pays? AB - Concern about financial ruin due to catastrophic illness has precipitated public policy actions resulting in the single largest expansion of the Medicare program by Congress since the program's inception. Using Kingdon's framework, significant participants and their actions are examined in the establishment of the health agenda and the selection of alternatives/solutions during development and passage of this legislation. During the final stages, decisions were largely driven by economics and politics, leaving many elderly persons confused and angered while many other more needy Americans are still at risk for financial ruin due to catastrophic illness. PMID- 2193966 TI - The National Library of Medicine--a treasure trove for nurse researchers. PMID- 2193967 TI - AAHN--the birth of an organization. PMID- 2193968 TI - The classification of patient outcomes. PMID- 2193969 TI - Immunology of the external ocular tissues. PMID- 2193970 TI - Mechanisms, diagnosis, and management of common ocular allergies. PMID- 2193971 TI - Giant papillary conjunctivitis. PMID- 2193972 TI - Clinical anatomy of the external eye. PMID- 2193973 TI - A model of mourning: change in schemas of self and other. AB - The mourning process may serve an evolutionary purpose, one that has allowed maximum survival characteristics. By passage through the phases of grief, the bereaved person prepares to make new commitments to others and to accept new personal roles. This passage involves an unconscious change in mental structures of meanings about the self and other people. This paper examines mourning in terms of such person schemas. PMID- 2193974 TI - The analytic surface and the theory of technique. AB - This paper examines the concept of the analytic surface as a starting point for the interpretive process in relation to the theory of psychoanalytic technique. The history of the concept of the analytic surface within psychoanalysis is reviewed. Four different conceptualizations of analytic surfaces are described (M.M. Gill, P. Gray, A. Kris, E.A. Schwaber). The advantages of a "surface" approach are explored in relation to clinical work, the teaching of psychoanalytic technique, and opportunities for research. Some criticisms of the concept are explored. PMID- 2193975 TI - Psychoanalytic observation. AB - The recent focus on empathy as the essential activity in psychoanalytic data gathering has underemphasized the complexity of psychoanalytic observation and has failed to identify what truly makes it unique among modes of psychological investigation. It is a process that includes introspection and empathy. However, it also includes the analyst's observation of the patient's behavior, and particularly verbal behavior, in a way that is not necessarily empathic. The psychoanalytic use of introspection and behavioral observation together, as they are modified by the analysand's free association and the analyst's evenly hovering attention, provides a unique method of data gathering. The transient, mutually related regressions of analyst and analysand which partly constitute the analyzing instrument modify the field of observation available to both, providing better access to derivatives of the analysand's unconscious mental functioning. This more complex concept of psychoanalytic observation, as opposed to that in which empathy is predominant, has important implications for psychoanalytic training, clinical work, and theory. PMID- 2193976 TI - The transference neurosis in Freud's writings. AB - This paper reviews the evolution of the concept of transference neurosis in Freud's writings. It suggests that the language in which the concept of the transference neurosis is originally expressed by Freud includes an idea of the analyst as aggressively pursuing the analytic cure by waging a solitary battle against the patient's disease. With the representation of the death drive and the larger role accorded to sadism as its external manifestation in Freud's revised drive theory of 1920, the patient becomes the ally; resistance, in the sense of the conservative forces, not disease, in the sense of libidinal conflict, becomes the enemy. It is thus difficult to speak of a transference neurosis in the circumscribed way Freud originally meant it, and he ceased to use the term after 1926 rather than redefine it to fit his broader perspective. In this broader perspective, relative resolution of conflict replaced radical liberation of the patient from disease. That Freud did not redefine the term does not imply that he discarded it, or that we necessarily should. This paper suggests that Freud implied a functional distinction between transference as transforming agent and transference neurosis as result of that transformation. That distinction defines psychoanalytic cure in terms of the understanding of a symbolic transformation which is, through the transference neurosis, reexperienced as part of the psychoanalytic process. PMID- 2193977 TI - Introducing psychiatric residents to psychoanalysis: a visiting analyst's perspective. AB - The serious decline in applicants for psychoanalytic training mandates the attention of psychoanalytic educators. If students are to be drawn to psychoanalysis, creative methods must be employed to convey the vigor and excitement of work in the field. The author describes two experiences as a visiting analyst, in a university hospital psychiatric residency in which there is almost no regular exposure to psychoanalytic thinking. Because he was dissatisfied with an approach that stressed literature review and psychotherapy case presentations and supervision, he developed a teaching technique through which he was able to show the residents how he thought analytically and self analytically. This teaching method is discussed in terms of Stein's (1988) injunction that analysts reveal more about the process of their thinking when they write, his description of how Bertram D. Lewin taught by encouraging analytic candidates to free-associate as a method of understanding new case material, and Arlow's (1972) view of the centrality of identification in education. PMID- 2193978 TI - Toxicology update isoparaffinic hydrocarbons: a summary of physical properties, toxicity studies and human exposure data. AB - The Isoparaffins covered in this manuscript are branched aliphatic hydrocarbons with a carbon skeleton length ranging from approximately C10 to C15. They are used in the manufacture of liquid imaging toners, paint formulations, charcoal lighter fluid, furniture polishes and floor clearners. Potential exposure exists in the petroleum, printing and paint industries. Isoparaffins have a very low order of acute toxicity, being practically non-toxic by oral, dermal and inhalation routes. However, aspiration of liquid isoparaffins into the lungs during oral ingestion could result in severe pulmonary injury. Dermally, isoparaffins have produced slight to moderate irritation in animals and humans under occluded patch conditions where evaporation cannot freely occur. However, they are not irritating in non-occluded tests, which are a more realistic simulation of human exposure. They have not been found to be sensitizers in guinea pig or human patch testing. However, occasional rare idiosyncratic sensitization reactions in humans have been reported. Instillation of isoparaffins into rabbit eyes produces only slight irritation. Several studies have evaluated sensory irritation in laboratory animals or odor or sensory response in humans. When evaluated by a standard procedure to assess upper airway irritation, isoparaffins did not produce sensory irritation in mice exposed to up to 400 ppm isoparaffin in air. Human volunteers were exposed for six hours to 100 ppm isoparaffin. The subjects were given a self-administered questionnaire to evaluate symptoms, which included dryness of the mucous membranes, loss of appetite, nausea, vomiting, diarrhea, fatigue, headache, dizziness, feeling of inebriation, visual disturbances, tremor, muscular weakness, impairment of coordination or paresthesia. No symptoms associated with solvent exposure were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2193979 TI - A single-blind pilot study comparing standard and half bedtime doses of ranitidine in the short-term healing of duodenal ulcer. AB - In this two-center, pilot trial we assessed the efficacy of single bedtime does of 150 mg ranitidine (half dose) and 300 mg ranitidine (full dose) in promoting duodenal ulcer healing by comparing the proportions of healed ulcers after 4 and 8 weeks of treatment. One hundred thirty-nine patients (106 men) were randomly allocated according to a prearranged treatment schedule to either dose and were treated single-blind (endoscopist). One hundred twenty-six patients (63 given 150 mg ranitidine and 63 given 300 mg) completed the trial. In the per-protocol analysis, 55 patients given full doses (81%) and 47 given half doses (70%) of ranitidine had healed ulcers at 4 weeks. Sixty full-dose and 55 half-dose patients (95% and 87%, respectively), had healed ulcers at 8 weeks. The difference was not significant using the chi 2 test (two-tailed), but the 95% confidence limits were in favor of the 300-mg dose. This study had a 75% power to detect a 25% difference in healing rates between the two groups. PMID- 2193980 TI - The effect of chronic aspirin use on duodenal and gastric ulcer hospitalizations. AB - Aspirin is commonly accepted as a risk factor for gastric ulcer; however, there is little published evidence linking aspirin consumption to duodenal ulcer. The effect of 1 g of aspirin per day on site-specific ulcer hospitalizations was examined using data from a 3-year randomized, double-blind, placebo-controlled trial of 4,524 subjects (Aspirin Myocardial Infarction Study). There were 23 duodenal ulcer and 14 gastric ulcer hospitalizations during the follow-up period. All but two were verified by endoscopy, radiogram, or biopsy/surgery. For males, a Cox-model survival analysis showed that the age- and smoking-adjusted relative risk for duodenal ulcer hospitalization was 10.7 times higher for the aspirin group than for the placebo group (95% confidence interval, 2.5 to 45.5; p less than 0.0001). The adjusted relative risk for gastric ulcer was 9.1 (95% confidence interval, 1.2 to 71.4; p = 0.04). Due to the small number of females in the study, the relationship between site-specific ulcer and aspirin consumption for females was not analyzed. However, for males and females combined, the age-, smoking-, and sex-adjusted relative risk for peptic ulcer hospitalization was 7.7 (95% confidence interval, 2.7 to 21.7; p less than 0.0001). We conclude that chronic aspirin use is a risk factor for hospitalization for both duodenal and gastric ulcer in males, and for peptic ulcer in males and females. PMID- 2193981 TI - Clinical significance of biliary sludge. AB - Although biliary sludge has been considered to be a benign condition associated with factors promoting bile stasis, its clinical significance and whether it contributes to biliary tract symptoms are uncertain. We conducted a retrospective review of patients with ultrasonographic diagnosis of biliary tract sludge during the 6-year period from 1979 to 1985. Of the 87 patients with gallbladder sludge alone, 11 (13%) had definite clinical findings and evolving laboratory abnormalities consistent with acute biliary tract disease. Four of these 11 patients proved to have gallstones at the time of surgery, while three had sludge alone as the apparent cause of their biliary tract symptoms. The clinical illness in four remaining patients resolved with medical therapy. We conclude that gallbladder sludge, as defined by ultrasound, may be associated with acute biliary tract disease. PMID- 2193982 TI - Leiomyoblastoma of the jejunum. AB - A 35-year-old male with the symptoms of acute abdomen proved to have a jejunal leiomyoblastoma. We renew recommendations for treatment by wide excision and regional lymphadenectomy. PMID- 2193983 TI - Solid and papillary epithelial neoplasm of the pancreas: clinical findings of a rare tumor. AB - A young woman presented with a large pancreatic mass that was found to be a solid and papillary epithelial neoplasm. The endoscopic, radiologic, and gross appearance of this tumor is described. The origin of the tumor is probably from a multipotential stem cell of the pancreas. Surgical resection is usually curative, although radiotherapy and chemotherapy have been successfully used. This unusual tumor should be considered in the differential diagnosis of a young female with a pancreatic mass. PMID- 2193984 TI - Chlamydia trachomatis peritonitis: another cause of protein-rich lymphocytic ascites. AB - Ascites as a main feature of Chlamydia trachomatis infection in two young women was successfully treated with doxycycline. In both patients, ascitic fluid protein levels and lymphocyte counts were very high. This report, as well as six previously published cases, suggest that ascitic fluid culture for C. trachomatis and blood antibody determinations should be performed in all cases of protein rich lymphocytic ascites in sexually active women. PMID- 2193985 TI - Hemoperitoneum due to a ruptured gastroepiploic artery aneurysm in systemic lupus erythematosus. A case report and literature review. AB - A 52-year-old woman with systemic lupus erythematosus (SLE) had a hemoperitoneum following a ruptured dissecting aneurysm of the right gastroepiploic artery. We believe this event has been reported only eight times before, but this is the first time it has been associated with SLE. PMID- 2193986 TI - Peridiverticulitis of the appendix: an unusual ultrasonic "target lesion". AB - In a 26-year-old man with perforating diverticulitis of the appendix ultrasonography demonstrated a "target lesion" with a hyperechoic center surrounded by a hypoechoic rim similar to the findings commonly seen in benign and malignant conditions of the gastrointestinal tract. This ultrasonographic appearance is quite different from the ultrasonic findings usual in acute appendicitis. We take this to be the first ultrasonic demonstration of appendiceal diverticulitis, and discuss the clinical features, ultrasonic differential diagnosis, and pathology of this condition. PMID- 2193987 TI - Semiquantitative assessment of cholestasis and lymphocytic piecemeal necrosis in primary biliary cirrhosis: a histologic and immunohistochemical study. AB - Histologic activity of chronic cholestasis and lymphocytic piecemeal necrosis, a characteristic finding of chronic active hepatitis, was examined semiquantitatively in 157 liver biopsy specimens from 122 patients with primary biliary cirrhosis (PBC). Although both of these lesions were usually admixed variably in a single liver specimen, semiquantitative assessment made it possible to classify liver biopsy specimens into four groups: group A, no or minimum cholestatic or hepatitic changes (58 specimens); group B, predominantly cholestatic changes (37 specimens); and group C, predominantly hepatitic changes (54 specimens). Only eight specimens fell into group D, prominent cholestatic as well as hepatitic changes. Serial liver biopsies of specimens within groups B and C showed a persistence of group B- and C-type pathologies, while liver biopsies of group A specimens frequently changed to group B or C. Immunohistochemical studies illustrated that lymphocytic piecemeal necrosis mainly consisted of activated T lymphocytes as seen in chronic active hepatitis. Our data suggest that either of two hepatic parenchymal lesions predominates and persists in each liver biopsy specimen. A high cholestatic score appeared to relate to poor prognoses of the patients and also to the degree of cirrhotic transformation. This grouping system may be valuable in the clinicopathologic assessment of PBC, when it is combined with ordinary staging. PMID- 2193988 TI - The administration of rectal diazepam for acute management of seizures. AB - The emergency management of seizures often involves the use of diazepam as a first-line medication. Intravenous access is difficult in pediatric patients who are having seizures, and for this reason alternate routes of administration have been sought. This paper reviews the recent literature concerning the efficacy of rectal administration of intravenous diazepam solution for the purpose of emergency management of seizures in children. Although intravenous diazepam is the preferred route for the child with active seizure activity, undiluted diazepam intravenous solution administered per rectum is an excellent alternative. The technique of administration is reviewed. PMID- 2193989 TI - Coronary atherosclerotic heart disease--a review for the general practitioners. PMID- 2193990 TI - [Routine kidney function tests for the diagnosis of kidney diseases]. PMID- 2193991 TI - [Pathology of glomerulonephritis]. PMID- 2193992 TI - [Treatment and physiopathology of diabetic nephropathies]. PMID- 2193993 TI - Systemic absorption of ocular scopolamine in patients. AB - The systemic absorption of scopolamine 0.25% eyedrops given unilaterally was quantitated in eight patients following therapeutic drug application. Another set of eight patients received placebo drops to study the effect of scopolamine on heart rate, blood pressure and salivation. Scopolamine was rapidly and efficiently absorbed after its ocular administration. The peak plasma scopolamine concentration of 550 +/- 60 pg/ml was reached within 15 minutes in all but two patients. Ocular scopolamine did not affect patients blood pressure or heart rate when compared to patients in the placebo group. Thirty minutes after administration of scopolamine the salivary secretion was slightly but insignificantly reduced. PMID- 2193994 TI - Development of D-timolol for the treatment of glaucoma and ocular hypertension. AB - It has been found that D-timolol is equipotent or slightly less potent than L timolol to lower the intraocular pressure (IOP) in normotensive rabbits, water loaded ocular hypertensive rabbits, alpha-chymotrypsin induced glaucoma rabbits, hypertonic saline infused IOP recovery model of rabbits, normotensive human volunteers, glaucoma patients and ocular hypertensive human individuals. Although L-timolol has been used widely for the treatment of glaucoma and ocular hypertension, it produces numerous side effects including cardiovascular disturbances, asthmatic attack, psychological depression, etc. Since D-timolol has much weaker affinity toward beta-adrenergic receptors, it was found to have 1/80-1/300 the beta-adrenergic blocking potency of L-timolol to block beta adrenergic receptors in guinea pig tracheal preparations and 1/90 of L-timolol to block beta-adrenergic receptors in guinea pig atrial preparations. As a result, D timolol showed no subjective nor objective side effects on pupil size, conjunctiva, cornea, blood pressure and pulse rate. Further, D-timolol was reported to increase retinal and choroid blood flow in rabbits without affecting overall ocular blood flow. On the contrary, L-timolol was found to significantly reduce the overall ocular blood flow and retinal and choroid blood flows in rabbits, although it might slightly increase the retinal blood flow in normotensive individuals. D-Timolol was well absorbed across the cornea as L timolol and produced the duration of action as long as L-timolol. These results indicate that D-timolol could be a better agent than L-timolol for the treatment of glaucoma and ocular hypertension. PMID- 2193995 TI - Radiology corner. Appendicitis. PMID- 2193996 TI - Does patient education cause side effects? A controlled trial. AB - Ninety-eight adults treated with erythromycin for a variety of illnesses were randomized to two groups: the informed group received patient education about drug side effects, and the uninformed group were given no such information. Overall, 10% of the uniformed and 8% of the informed group felt the erythromycin bothered them in some way. There were no significant differences in the occurrence of various individual side effects. Compliance with therapy and the results of treatment were the same for both groups. In this study, informing patients about side effects of therapy did not have any detectable adverse effects. PMID- 2193997 TI - Adult respiratory distress syndrome complicating recurrent antepartum pyelonephritis. PMID- 2193998 TI - The efficacy and safety of imipenem/cilastatin in the treatment of severe bacterial infections. AB - We have assessed the efficacy and safety of imipenem/cilastatin in a non comparative study of 27 immunocompromised patients suffering from severe bacterial infections. Moreover in two groups of 14 patients the efficacy of imipenem/cilastatin versus a standard broad spectrum antibiotic therapy has also been compared. Clinical and microbiological efficacy and side effects have been evaluated. PMID- 2193999 TI - Multimodal biochemical modulation of 5-fluorouracil activity in advanced colorectal cancer with allopurinol, folinic acid and dipyridamol. AB - It is now commonly accepted that the activity of 5-fluorouracil (5FU) may be potentiated by folinic acid (FA). Moreover dipyridamol (DIP) interacts with the pyrimidine salvage pathway of 5FU. In 28 patients with advanced colorectal cancer, in progression under FA-5FU, we continued treatment with FA-5FU plus DIP. FA 200 mg/m2/day. i.v. push was given before 5FU 766.52 mg/m2/day (mean dose), in 60 min infusion for 5 subsequent days. Cycle was repeated every 21 days. We noticed greater but not seriously increased toxicity by the addition of DIP. The addition of DIP did not change response rates; it seemed to increase response but not significantly. PMID- 2194000 TI - Immunologic and morphologic typing as prognostic factor in M1 acute myeloblastic leukemia. AB - Thirty-two patients diagnosed in the Gustave Roussy Hospital between 1981 and 1988 were divided into three groups according to the morphology of the predominant blast cells in the bone marrow. Cytochemical reaction in the form of Sudan Black, myeloperoxidase reaction and immunological typing were performed for 13 patients. Twelve patients were treated with protocol AML6, eight with protocol AML8, one with protocol LAL16, and the rest with other types of protocols. To a certain extent morphological maturation was correlated with antigenic differentiation. The lack of expression of Ia antigen (HLA-DR) identified patients with a low rate of relapse during the first year of remission, and patients with My7 positive leukemia had a worse prognosis than did patients with My7 negative leukemia. The 2 patients positive for MO1 antigen did not achieve remission, and out of 9 patients who were negative for MO1 antigen only 2 achieved remission for approximately 1 year. Only 1 of 3 patients with biphenotypic leukemia achieved remission for more than 1 year. PMID- 2194001 TI - Influence of antibiotics on host-parasite interactions with an emphasis on in vivo studies. AB - There has been considerable recent interest in the nature and importance of interactions which occur between antibiotics, microorganisms and the various cellular and humoral components of the host. The influence of antibiotics on host defense mechanisms is important because of the increasing number of compromised hosts in whom even a marginal influence on the host response may have a significant effect of the outcome. The influence of antibiotics on host/bacterial interaction reveals subtle effects on the ultrastructure of the bacterial cell, the biosynthesis of various virulence factors, the ability of microorganisms to adhere to epithelial cells and the function of polymorphonuclear leukocytes and the immune-specific response of mononuclear cells. These effects permit the proposal that at least some of the subtle effects of antibiotics on microbial pathogenicity might take place in vivo. If antibiotics can be shown definitely to enhance host-defense mechanisms, especially in compromised hosts, then more effective antibiotic therapy can be provided for these indications. Finally if antibiotics can modify the outcome of host-parasite interactions then perhaps we need to consider testing antibiotics against these parameters. PMID- 2194002 TI - Concepts and trends in antiviral chemotherapy in the period of AIDS: a review. AB - The spread of acquired immune deficiency syndrome (AIDS) in man has accentuated the need for an effective drug against the human immunodeficiency virus (HIV). The inability of devising a vaccine to stop the spread of the virus and its ability to damage the immune response in infected individuals has increased the need for effective antiviral agents. The present review analyzes the approaches that have led to the development of effective anti-herpes simplex virus chemotherapy. The emerging concepts in antiviral chemotherapy such as interference with HIV-1 attachment to its cellular receptor CD4 are presented and the current state of research on antiviral agents is evaluated. PMID- 2194003 TI - Quantitative analysis of tomographic stress thallium-201 myocardial scintigrams: a multicenter trial. AB - The accuracy of the previously developed and validated Cedars-Sinai Medical Center (CSMC) computer program for quantitative analysis of thallium-201 (201TI) stress myocardial tomograms was assessed in a multicenter trial consisting of 242 patients with coronary angiography and 76 with a low likelihood (LL) of coronary artery disease (CAD) involving various cameras, computers, and operators. The program utilized gender-matched normal limits developed from 35 LL patients at CSMC. The multicenter results as compared to those of 168 patients from CSMC were not significantly different with respect to the overall sensitivities (94% versus 95%) and specificities (44% versus 56%) for identification of CAD and normalcy rates which were determined in LL patients (82% for both) and with respect to identification of individual diseased arteries. The results indicate that our method for quantifying tomographic 201TI stress scintigrams utilizing standard normal limits can be applied at other institutions by different operators, using a variety of cameras and computers, with similar accuracy to that currently obtained at our institution. PMID- 2194004 TI - The therapeutic efficacy of oral cholecystographic agent (iopanoic acid) in the management of hyperthyroidism. AB - Five randomly chosen patients with thyrotoxicosis were administered 1 gm of the oral cholecystographic agent iopanoic acid daily for 21 days. There was a marked fall in T3 levels by 75% of the pretherapy value by 96 hr; values remained normal over the 21-day period. T4 values fell significantly by seven days of therapy, and the decreased values were sustained. FT3 and FT4I also showed corresponding decreases in value. All subjects showed clinical improvement by both subjective and objective criteria. During therapy, escape from the effect of iopanoic acid was not encountered. However, after stopping the drug for 2-4 wk, the patients' iodine-131 uptake become as high as the pretherapy level, enabling them to undergo radioiodine treatment for thyrotoxicosis. The treatment strategy can be aimed at achieving quick euthyroidism and in planning radioiodine treatment as early as possible in high risk patients. This treatment may also be useful in preoperative control of thyrotoxicosis. PMID- 2194005 TI - Methods for measuring GFR with technetium-99m-DTPA: an analysis of several common methods. AB - Several commonly used scintigraphic methods of GFR measurement were evaluated. Forty-three adult patients with a wide range of ages and renal function were studied. The two-sample plasma method of Russell and the urinary method of Jackson were the most accurate methods overall. The one-sample plasma method of Russell, the volume of distribution method of Fawdry, and a terminal slope method were less reliable, especially at low (0-60 ml/min) GFRs. The renal uptake method of Gates correlated poorly to the standards at all GFR levels even when corrected for body surface area or blood volume. The Russell two point and Jackson urinary GFR's can be used as complementary techniques and are recommended as primary methods of scintigraphic GFR determination. PMID- 2194006 TI - Thomas P. Haynie, MD, honored as distinguished educator. PMID- 2194007 TI - Michigan brain imaging researcher receives 1990 Tetalman Memorial Award. PMID- 2194008 TI - Intestinal ischemia and necrotizing enterocolitis. PMID- 2194009 TI - Gastrointestinal host defense and necrotizing enterocolitis. PMID- 2194010 TI - Role of bacterial toxins in neonatal necrotizing enterocolitis. PMID- 2194011 TI - Necrotizing enterocolitis: role of platelet activating factor, endotoxin, and tumor necrosis factor. PMID- 2194012 TI - Colonic fermentation of carbohydrate in the premature infant: possible relevance to necrotizing enterocolitis. PMID- 2194013 TI - Effects of bacterial fermentation end products on intestinal function: implications for intestinal dysfunction. PMID- 2194014 TI - Intraluminal pathogenesis of necrotizing enterocolitis. PMID- 2194015 TI - Hyalohyphomycosis by Paecilomyces lilacinus in a renal transplant patient and a review of human Paecilomyces species infections. AB - A case of hyalohyphomycosis caused by Paecilomyces lilacinus is described in a renal transplant patient. Infection was localized on the left forearm. Two separate cultures of the lesions yielded the same organism. Histological sections disclosed hyaline elements in the tissue. The infection responded well to therapy with oral griseofulvin (500 mg daily) and the patient was cured within 45 days. Forty-six cases of human infection due to Paecilomyces species have been reported previously in the literature, most of them occurring in conjunction with prosthesis implants or immunosuppression. The antifungal sensitivity of Paecilomyces varies widely among the species but the general trend is for Paecilomyces variotii isolates to be almost universally sensitive to amphotericin B and 5-fluorocytosine, while P. lilacinus and Paecilomyces marquandii isolates are resistant to these antifungals but sensitive to the imidazoles. PMID- 2194016 TI - Pathogenicity of 5-fluorocytosine resistant strains of Candida albicans. AB - Mutants of Candida albicans blocked in pyrimidine transport and salvage metabolism were produced by a two step mutagenic procedure and selected by their resistance to 5-fluorocytosine (flucytosine). The growth rates and growth yields of these mutants did not differ significantly from the parental strain of C. albicans. Examination of their pathogenicity to mice demonstrated that a defect in the uridine transport function decreased the pathogenicity of C. albicans. PMID- 2194017 TI - Demonstration of fungal proteinase during phagocytosis of Candida albicans and Candida tropicalis. AB - The extracellular acid proteinase of Candida albicans and Candida tropicalis was monitored in vitro during phagocytosis by murine peritoneal macrophages. Fungal blastospores were quickly ingested by the thioglycolate-elicited macrophages and the intracellular blastospores partly resisted killing and started to grow out after 6 h incubation, causing destruction of the macrophage. Proteinase antigen appeared on fungal cells after 30 min in culture medium containing 10% fetal calf serum. The antigen was detected on ingested blastoconidia and filamentous cells of C. albicans serotype A. The proteinase antigen was also expressed by blastoconidia of C. albicans serotype B but was missing on the filamentous cells of this serotype. Isolates of C. tropicalis behaved similarly to C. albicans serotype A. The acid proteolytic activity of Candida cells was confirmed by the haemoglobin test on culture supernatants. Lysates of infected and noninfected phagocytes showed a differential acid proteolytic activity; noninfected macrophages revealed rising activity, while infected macrophages showed a distinct reduction of activity. The proteolytic activity of lysates of noninfected cells is due to lysosomal cathepsin-D. Cathepsin-D was also most likely to be responsible for the declining proteolytic activity in lysates from infected phagocytes; such lysates contained increasing amounts of fungal proteinase antigen. The differential kinetics of this antigen and the total acid proteolytic activity in the lysates suggest a conflict between microbial and lysosomal hydrolases in infected phagocytes. The outcome of this conflict depends on the number and hydrolytic activity of the ingested yeasts and may be decisive in the progress of infection. PMID- 2194018 TI - The use of flow cytometry to monitor chitin synthesis in regenerating protoplasts of Candida albicans. AB - Flow cytometry was used to monitor chitin synthesis in regenerating protoplasts of the yeast Candida albicans. Comparisons of cells stained with Calcofluor White, a fluorochrome with known affinity for chitin, and cells incubated in the presence of N-[3H]-acetylglucosamine, the precursor substrate for chitin, showed a linear relationship between fluorescence and incorporation of label over time. Changes in both the fluorescence and light scatter of regenerating protoplasts treated with inhibitors of fungal chitin synthase were also quantitated by flow cytometry. PMID- 2194019 TI - Fracture resistance of amalgam coronal-radicular restorations. AB - The effect of pulp chamber depth and extension into the root canal space on fracture resistance was examined on endodontically treated teeth with coronal radicular amalgam restorations. Six groups of 10 mandibular molars were mounted in acrylic resin, and crowns were ground apically until the wall height of the pulp chamber was 2, 4, or 6 mm. Three millimeters of gutta-percha was removed from the three canals of one-half the teeth and amalgam was condensed into the canal space to a height 7.5 mm above the cementoenamel junction (CEJ). The remaining teeth had amalgam condensed from the floor of the chamber to 7.5 mm above the CEJ. The amalgam restorations were loaded with an Instron instrument (Instron Corp., Canton, Mass.) until failure. Amalgam extension into the root canal space contributed minimally to the fracture resistance of the amalgam coronal-radicular restoration with four or more millimeters of chamber wall. If less than 4 mm of chamber wall height remained, however, the fracture load was substantially increased. Amalgam extension into the root canal space should be confined to teeth with limited remaining pulp chambers. PMID- 2194020 TI - Amalgam crown restorations for posterior pulpless teeth. AB - Cast restorations are the usual technique chosen for the restoration of posterior pulpless teeth. Complex amalgam restorations are suggested as an alternative method of treatment, and several advantages are described. Techniques to provide sufficient retention and resistance form include the use of threaded pins, amalgapins, slots and grooves, amalgam in the pulp chamber, or canals, or both, and posts cemented within the canals. The practicing clinician is advised to become familiar with these retention techniques so that difficult retention situations may be treated effectively. PMID- 2194021 TI - Conservative posterior ceramic restorations: a literature review. AB - Conservative ceramic restorations have much to offer to improve appearance and strengthen posterior teeth. The advent of resin bonding makes possible many designs for inlays, onlays, and partial coverage crowns. This review discusses conventional porcelain, Optec HSP porcelain, Dicor, and Cerapearl with emphasis on strengthening mechanisms, principles of preparations, accuracy of fit, and indications. PMID- 2194022 TI - Effect of multiple firing on the bond strength of selected matched porcelain fused-to-metal combinations. AB - In this study two different opaque porcelain-metal combinations were evaluated for planar shear bond strength. Samples were tested after one, three, five, seven, and nine different firing cycles to evaluate the effect of repeated firing on shear bond strength. For the combination of Will Ceram/W1 and Vita/Olympia materials, no statistical difference was observed either between materials or after repeated firing. For apparently well-matched porcelain-metal combinations, no significant reduction in bond strength occurs during normal firing of the opaque porcelain to the metal. PMID- 2194023 TI - Altered corrosion resistance from casting to stainless steel posts. AB - Heat treatment during the burnout procedure may cause corrosion of the stainless steel post. This study was undertaken to determine whether alteration of the corrosion resistance of stainless steel posts occurs as a result of various simulated burnout procedures. Stainless steel posts were divided into five groups of five posts: group 1, control; 2, gypsum-bonded investment, bench cooled; 3, gypsum-bonded investment, quenched; 4, phosphate-bonded investment, bench cooled; and 5, phosphate-bonded investment, quenched. The posts were placed in individual containers of Ringer's solution and observed at 30, 180, and 600 days. Scanning electron microscopy, energy dispersive x-ray spectroscopy, optical emission spectroscopy, and optical microscopy were used to evaluate the posts qualitatively and quantitatively. Investment and heat treatment altered the metallic structure of stainless steel posts. Prefabricated posts submitted to simulated burnout procedures had a noticeable reduction in corrosion resistance. Direct casting to stainless steel posts is contraindicated. PMID- 2194024 TI - A qualitative study for the bond and color of ceramometals. Part I. AB - A shear testing method was devised to study and evaluate the effect of various and repeated firing cycles, types of alloy, and brand of porcelain relative to the color and bond strength of ceramometal complexes specifically at the opaque porcelain-metal interface and the opaque-body porcelain juncture. Two alloys and two porcelain brands were chosen on the basis of their widespread clinical use and the marked contrast between them. An increase of the firing temperature significantly raised the bond strength for all alloy-porcelain combinations. PMID- 2194025 TI - Three-dimensional stability of new denture base resin systems. AB - Ten maxillary dentures were constructed on standard-sized casts in each of four acrylic resins. Uniform placement of the artificial teeth and thickness of the base were maintained by use of a silicone rubber mold. Metal shot was luted in preselected positions to the dentures and the land of the cast. Frontal, lateral, and occlusal radiographs were made of the dentures at time intervals of (1) before processing, (2) after processing, (3) immediately after removal from the cast, and (4) 30 days later. Study of the radiographs revealed significant variations in position of the metal shot from the before-processing baseline within each group of dentures and significant differences between groups of dentures. PMID- 2194026 TI - An innovative method of monitoring denture hygiene. AB - A simple and rapid test for measuring oral hygiene was recently developed. It is based on the rate of oxygen consumption of oral expectorates of milk. This investigation modified the test to study denture hygiene. The dentures of 20 patients were immersed in 10 mL of sterile milk. After a 2-minute agitation, 3 mL of milk was added to test tubes containing methylene blue. The time required for color change at the bottom of the test tube, which is indicative of the rate of oxygen consumption, was recorded. For comparison with visual plaque accumulation, the dentures were coated with disclosing solution and the extent of plaque was scored by three examiners. A correlation was found between the plaque index scores and results of the milk test (r = -0.64; p less than 0.005). The data suggests the use of this test to monitor denture hygiene. PMID- 2194027 TI - Slip-cast zirconia dental roots with tunnels drilled by laser process. AB - Zirconia was used in this study for implant dental roots because of its superior properties over other materials used as dental roots in mechanical strength, toughness, workability, and biocompatibility. Zirconia blades were formed by the slip casting method and tunnels were drilled in the laser processing. The results indicate that (1) the slip casting method has made it possible to form a complicated artificial dental root with an accurate shape and size; (2) the zirconia blade has adequate strength in occlusion; (3) the neodymium: yttrium aluminum-garnet (Nd:YAG) laser machine can drill many tunnels of the same size in diameter by using it repeatedly under the same conditions of power, pulse width, and focus; (4) zirconia is a recommended material for laser processing from the standpoint of toughness and less heat conductivity; and (5) the opacity of zirconia to x-ray penetration presents better observation during and after implantation than other ceramics. PMID- 2194028 TI - Composite resin contouring of abutment teeth for rotational path removable partial dentures. PMID- 2194029 TI - Antihypertensive therapy and quality of life: a comparison of atenolol, captopril, enalapril and propranolol. AB - This randomized, double-blind parallel study compared the effects of atenolol, captopril, enalapril and propranolol in 360 men with mild-to-moderate essential hypertension. Patients were titrated until diastolic blood pressure (Korotkoff phase V) decreased by at least 10 mmHg or to 90 mmHg or less. Quality of life assessments, based on validated psychometric questionnaires and objective measurements of cognitive function, occurred after three study phases: placebo run-in (3-5 weeks), titration (1-4 weeks), and maintenance (4 weeks). After four weeks of maintenance therapy, atenolol, captopril and enalapril generally had equivalent effects on quality of life, as measured by psychometric questionnaires, whereas propranolol consistently evidenced worsening or less improvement. Global scores of distressing psychological symptoms differed as a function of specific treatment (P = 0.01), with improvements significantly better for the atenolol, captopril and enalapril groups as compared with the propranolol group. There were no statistically significant differences among treatments for changes in cognitive function at maintenance. Thus, the quality of life questionnaires differentiated among drugs of the same class, indicating that selection among antihypertensive drugs should be based on their specific qualities, not on general class characteristics. PMID- 2194030 TI - Increased pulse pressure and carotid vascular resistance in normotensive black African subjects. AB - To evaluate ethnic differences in cerebral circulation, an index of carotid vascular resistance (RI) was determined by continuous wave Doppler ultrasound. Validation of the index resulted from a significant correlation between RI and carotid vascular resistance obtained from direct measurement of blood pressure and carotid blood flow by means of range-gated pulsed Doppler (r = 0.64; P less than 0.01). We studied 37 normotensive men: 17 white and 20 black. The two populations were age, sex, body mass index and mean arterial pressure matched. In blacks, a significant higher RI was observed (74.10(-2) +/- 1.6.10(-2) versus 64.10(-2) +/- 1.9.10(-2); P less than 0.001) together with a significantly higher pulse pressure (51 +/- 3 mmHg versus 43 +/- 2 mmHg) in comparison with whites. Our findings suggest that the higher prevalence of stroke in blacks might be related to significant haemodynamic characteristics of the carotid-cerebral circulation involving cerebral vasoconstriction. PMID- 2194031 TI - Effects of nephrectomy on hypertension, renin activity and total renal function in patients with chronic renal artery occlusion. AB - Eight hypertensive patients (5 men and 3 women, aged between 31 and 64 years) with chronic total occlusion of one renal artery were observed for the past ten years. The peripheral plasma renin activity (PRA) and the renal vein PRA ratio (mean 3.18) were abnormally high in all cases. Because of the small size of the affected kidney (less than 9 cm in length), nephrectomy was the chosen treatment. Postoperative investigations revealed decreases in blood pressure (from 202/118 to 147/93 mmHg), peripheral PRA (from 6.05 to 1.05 ng/ml/h; P less than 0.001), serum creatinine (from 188.8 to 145.1 mumol/100 ml) urine volume (from 1937.5 to 1214.3 ml) and increases in endogenous creatinine clearance (from 36.57 to 53.0 ml/min). The results suggest that, apart from the decrease in blood pressure, the nephrectomy led to the disappearance of a factor which depresses the renal function in cases of chronic renal artery occlusion and which may be related to the renin-angiotensin system. PMID- 2194032 TI - First-dose effects of enalapril and atenolol upon blood pressure and cerebral blood flow in patients with mild hypertension on diuretic therapy. AB - The present single-blind, randomised, cross-over, placebo-controlled study was set up to compare the first-dose effects upon blood pressure (BP) and cerebral blood flow (CBF, measured by Xenon inhalation) of a single oral dose of atenolol 50 mg and enalapril 5 mg in ten hypertensive patients receiving a thiazide diuretic. It was found that a) the timing and degree of fall in BP after the first dose of atenolol and enalapril on a diuretic background were similar and generally not associated with symptoms or a fall in CBF, and b) dizziness, which is sometimes associated with the first-dose effect of ACE inhibitors in hypertensives on diuretics, can occasionally occur accompanied by a substantial fall (43%) in CBF in the absence of marked falls in systolic blood pressure. It is suggested that the latter event may be linked to a disturbance of cerebral autoregulation in part dependent on localised renin-angiotensin systems. PMID- 2194033 TI - Water-soluble renin inhibitors: design of a subnanomolar inhibitor with a prolonged duration of action. AB - Incorporation of nonreactive polar functionalities at the C- and N-termini of renin inhibitors led to the development of a subnanomolar compound (21) with millimolar solubility. This inhibitor demonstrated excellent efficacy and a long duration of action upon intravenous administration to monkeys. While activity was also observed intraduodenally, a comparison of the blood pressure responses indicated low bioavailability. Subsequent experiments in rats showed that, although the compound was absorbed from the gastrointestinal tract, extensive liver extraction severely limited bioavailability. PMID- 2194034 TI - Improved tumor targeting with radiolabeled, recombinant, single-chain, antigen binding protein. PMID- 2194035 TI - Consensus on treatment of early stage breast cancer: less surgery, more research. PMID- 2194037 TI - Application of nuclear medicine techniques to the study of ARDS. AB - Radionuclide techniques used for the diagnosis and study of ARDS include the routine clinical procedures of perfusion lung scanning, gallium and white-cell imaging, as well as PET, indicator dilution methods for measuring extravascular lung water, and means of measuring protein accumulation, protein flux, and solute transfer. The techniques that reflect the rate of protein leak from the microvasculature and sensitive measures of rapidly reversible alveolar injury appear most promising. While clinical usefulness remains to be documented, these methods may ultimately assist with the diagnosis of ARDS and with the evaluation of prognosis and therapy. PMID- 2194036 TI - High-dose recombinant interleukin-2 alone: a regimen with limited activity in the treatment of advanced renal cell carcinoma. AB - Sixteen patients with metastatic renal cell carcinoma were treated with high-dose bolus recombinant interleukin-2 (rIL-2) alone at a dose and schedule identical to those that produced a 35% response rate among 72 patients in a trial reported by the Surgery Branch, National Cancer Institute (NCI), Bethesda, Md, in which rIL-2 plus lymphokine-activated killer (LAK) cells was used for the treatment of renal cell carcinoma. Patients received two 5-day cycles of 100,000 Cetus U/kg (600,000 IU/kg) of rIL-2 infused intravenously over 15 minutes every 8 hours; each treatment cycle was separated by 1 week. No objective responses were seen. The toxicity of rIL-2 given alone at these high doses was similar to that noted with high-dose rIL-2-LAK cell therapy. The lack of responses seen in this trial also differed from the 21% response rate observed by the NCI Surgery Branch, using rIL 2 alone at an identical schedule and dose in 56 patients with renal cell carcinoma. Only minor differences in such recognized prognostic variables as performance status, tumor burden, and rIL-2 dose intensity were noted between this study and other trials reported by the NCI Surgery Branch and by the IL-2 LAK Working Group. Our analysis indicates that, because of the smaller number of patients in our trial, not enough subjects were included with the ideal characteristics to attain the 21% response rate seen in the NCI study. However, the precise nature of these characteristics remains unclear. PMID- 2194038 TI - Cardiac imaging with technetium 99m-labeled isonitriles. AB - The 99mTc-labeled isonitriles are a new class of myocardial imaging agents that, because of superior physical characteristics, may be better for myocardial perfusion imaging than 201Tl, particularly with SPECT imaging modalities. The initial experimental and clinical experience with one of these radiotracers, 99mTc-MIBI, suggests that this radiotracer may be promising for the assessment of myocardial ischemia and infarction. The capability of assessing risk area during acute coronary occlusion and extent of myocardial salvage after reperfusion offers a noninvasive means to evaluate the efficacy of therapeutic interventions aimed at reducing ischemic myocardial injury. 99mTc-MIBI will provide a unique noninvasive means of simultaneously assessing myocardial perfusion and function, ultimately permitting a better understanding of ischemic-induced myocardial dysfunction. The analysis of the myocardial perfusion and function relationship may possibly provide a method of discriminating reversible myocardial ischemia from irreversible myocardial injury. Algorithms will need to be developed for the optimal quantification of 99mTc-MIBI images. Additionally, single-day protocols using split doses of 99mTc-MIBI will need to be further developed before 99mTc MIBI imaging can be widely employed. Although further clinical studies are necessary in larger numbers of patients before the full clinical implications of this radiotracer are known, the initial experience is encouraging. PMID- 2194039 TI - Imaging of the heart using metaiodobenzylguanidine. AB - Catecholamines have profound influences on cardiac function. Mechanisms relating abnormalities in sympathetic innervation to myocardial dysfunction are poorly understood, however. Recent studies have demonstrated the feasibility of noninvasively imaging the sympathetic nerves of the heart using radiolabeled MIBG. This article examines some of the experimental evidence to support the neuronal localization of MIBG. In addition, the early clinical experience is reviewed. PMID- 2194040 TI - Applications of exercise radionuclide ventriculography in the clinical management of patients with coronary artery disease. AB - Exercise radionuclide ventriculography is commonly used in patients with coronary artery disease, for both diagnostic purposes and patient management decisions. Both applications are reviewed in this article. There has been much debate as to the diagnostic efficacy of this test. Four factors influence this determination: (1) patient referral biases, (2) the optimal criteria for test interpretation, (3) the technique for performing radionuclide ventriculography, and (4) technical factors. The role of each factor is discussed. After consideration of these factors, it is concluded that the diagnostic efficacy of exercise radionuclide ventriculography is high. This test is used as a criterion for many patient management decisions, such as the need for coronary artery bypass surgery or coronary angioplasty. This test is well suited for such purposes because of its ability to quantitate the magnitude of ischemia. In addition to left ventricular ejection fraction, the importance of the following five wall motion variables are reviewed relative to the information they provide regarding ischemic magnitude: (1) extent, (2) magnitude, (3) time to onset and (4) duration of exercise-induced wall motion abnormalities, and (5) the paradoxical reversal of rest abnormalities following exercise. It is shown how consideration of all potential variables enhances the clinical utility of this test. PMID- 2194041 TI - Imaging techniques for assessing pulmonary artery hypertension and right ventricular performance with special reference to COPD. AB - Several imaging techniques, both noninvasive and minimally invasive, have now been applied widely for determining cardiovascular performance in patients with chronic respiratory disease, particularly COPD. Moreover, some of these techniques are useful for evaluating response to therapeutic intervention in these patients. The plain chest radiograph is useful primarily for detecting the presence of pulmonary artery hypertension in patients with COPD. Radionuclide angiocardiography, using either first-pass techniques or the gated equilibrium technique, is particularly useful for determining right and left ventricular ejection fraction. Echocardiography has evolved as a technique for assessing right ventricular size and function and, in some cases, the degree of pulmonary artery hypertension. PMID- 2194042 TI - The clinical role of radionuclide imaging in cardiac transplantation. AB - Cardiac transplantation is developing into a routine therapy with widespread availability. Nuclear medicine studies play an important role in evaluating potential transplant recipients and in providing documentation of the severity of ventricular dysfunction and the presence of ischemic but viable myocardium. Nuclear cardiology has increased our knowledge of the physiology of cardiac transplants and is now playing an increasing adjunctive role in management. Radionuclide ventriculography performed early after transplantation can identify patients both with abnormal biventricular function resulting from preservation injury and with isolated right ventricular dysfunction. It also provides important functional data that complements the cardiac biopsy in allograft rejection. New techniques such as 111In antimyosin antibodies and 111In lymphocytes have potential value for the accurate, noninvasive diagnosis of rejection. PET promises to improve the ability to diagnose coronary atherosclerosis of the allograft. PMID- 2194043 TI - Imaging of intrathoracic disease with indium 111-labeled leukocytes. AB - Indium 111-labeled leukocyte scintigraphy provides an excellent noninvasive means for identifying and localizing infectious and inflammatory sites within the body. This article first compares gallium 67 citrate, the long-established radiopharmaceutical for infection imaging, to 111In-labeled leukocytes, particularly as applied to the chest. 111In-labeled leukocytes require time consuming preparation, and the technical and practical aspects of cell labeling and imaging are reviewed in detail. The main focus of this article is the application of labeled leukocyte imaging to the evaluation of pleural, mediastinal, cardiovascular, and pulmonary disease. PMID- 2194044 TI - Cardiac positron emission tomography: the foundations and clinical applications. AB - Cardiac PET studies may have a role in the early detection of coronary artery disease. The early prediction of the ultimate fate of reperfused myocardium with cardiac PET imaging remains elusive. At present the predominant clinical use of PET scans lies in the identification of ischemic but viable tissue. Cardiac PET imaging with a combination of perfusion and metabolic tracers can distinguish those patients with a history of previous infarctions and severe heart failure who will benefit from therapeutic revascularization. Conversely, the group that is not expected to improve will be spared needless and risky attempts at revascularization and will become candidates for cardiac transplantation at an earlier stage. PMID- 2194045 TI - Plasma renin activity studies in a group of African neonates and children. AB - Plasma Renin Activity (PRA) was determined in a group of 50 Cameroonian newborns and 50 Cameroonian children aged 1-15 years under resting conditions in order to establish baseline values, and also to investigate the relationship between PRA distribution, and blood pressure levels, age, or body weight. Mean PRA values were 0.98 +/- 0.78 ng/ml/h at birth and 1.17 +/- 0.92 ng/ml/h in older children. These values did not correlate with birth weight, age, or blood pressure levels. These results are lower than figures reported in comparable groups of American white and black children, and also in European or Asian children. PMID- 2194046 TI - Diarrhoea due to intestinal parasites. PMID- 2194047 TI - Ineffectiveness of progesterone suppository treatment for premenstrual syndrome. AB - Progesterone is the most widely used treatment for premenstrual syndrome. To answer definitely the question of whether progesterone suppositories are effective for the treatment of premenstrual syndrome, a randomized, placebo controlled, double-blind crossover study of 168 women, receiving progesterone in doses of 400 and 800 mg or placebo, was carried out. Premenstrual symptoms were not significantly improved by progesterone compared with placebo in any measure used in the study, including daily symptom reports maintained throughout treatment, clinician evaluation of improvement, and patient global reports of symptoms severity, relief, and disruption of daily activity. No symptom cluster or individual symptom differed significantly between progesterone and placebo treatment. These treatment results were not significantly affected by fluctuations in response during the placebo washout period, pretreatment levels of depression or anxiety at either postmenstrual or premenstrual times, or any of 19 other background, medical history, or symptom variables examined individually as covariates with treatment. PMID- 2194048 TI - Alcohol and the cardiovascular system. AB - Ethanol has long been recognized as a toxic agent that has acute and chronic effects on cerebral and hepatic function. Over the past two decades important influences on the cardiovascular system have been either rediscovered or observed for the first time. The combined use of tobacco cigarettes and alcohol appears to increase the risk of many of these clinical abnormalities. While many individuals addicted to ethanol have subclinical abnormalities of the heart, somewhat less than a majority develop symptomatic cardiac problems. These include heart failure and arrhythmias. In addition to supraventricular arrhythmias that often normalize spontaneously, there is an increased incidence of sudden death that peaks at about 50 years of age in the alcoholic population. A significant degree of blood pressure elevation occurs in individuals who abuse alcohol. This appears to be transient and is normalized in most individuals during abstinence. The increased incidence of hemorrhagic and nonhemorrhagic stroke in middle age also appears to decline when alcohol abuse is interrupted. A preventive effect of mild to moderate drinking on coronary artery disease is, at present, equivocal, largely due to the question of appropriate controls. PMID- 2194049 TI - AMA-RPS chairperson looks back. PMID- 2194050 TI - A single ultrasound examination in pregnancy. PMID- 2194051 TI - [Laryngoscopy]. PMID- 2194052 TI - [Dermal patch anesthesia to prevent pain from dermal puncture--10% lidocaine aqueous gel with 3% glycyrrhetinic acid 3-0 hemiphthalate disodium]. AB - The clinical efficacies of 10% lidocaine aqueous gel with and without 3% glycyrrhetinic acid 3-0 hemiphthalate disodium (GAHPh) applied as a skin patch for reduction of pain from venous cannulation were evaluated in a double blind study. Twenty-four adult patients, who were scheduled for surgery under general anesthesia, gave informed consent to participate in this study. The patients were allocated randomly into two groups: one for a dermal patch GAHPh (GAHPh group) and the other for a dermal patch without GAHPh (plain group). Approximately 0.3g of either gel with or without GAHPh, soaked in a round sponge (25mm in diameter, 1mm in thickness), was applied over the selected vein on the arm and was covered with an adhesive plastic film (Tegaderm). Pain score was graded by the number of painful spots out of the 5 tests in the treated skin area. In patients with a pain score under 1, venous cannulation was carried out without an intradermal injection of a local anesthetic and pain associated with the cannulation procedure was graded by patients on a scale of 5, where 0 = no pain, 1 = little pain, 2 = moderate pain, 3 = painful, 4 = very painful. The mean application time periods were 59.3 min for the GAHPh group and 60.3 min for the plain group. Transient local redness was observed in 8 patients after removal of the gels; 3 in the GAHPh group and 5 in the plain group. The mean pain score (1.3 +/- 1.5) in the GAHPh group, was significantly lower than that (2.5 +/- 1.7) in the plain group (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2194053 TI - [Influence of intrathecal morphine and buprenorphine on EEG and their analgesic effect]. AB - This study was performed on fifty patients undergoing gynecological operations of lower abdomen. Their mean age and body weight were 43 +/- 5yrs and 55 +/- 8kg (mean +/- SD) respectively. All patients were given spinal anesthesia for surgery. Patients were divided into four groups of ten patients at random as follows: Group I (control) received 7.5mg of dibucaine only, Group II received 7.5mg of dibucaine with 0.05mg of buprenorphine (B), Group III received 7.5mg of dibucaine with 0.25mg of morphine (M), Group IV was the same as G-III but received 0.2mg of naloxone after operation. We observed EEG during operation and assessed intrathecal B and M for postoperative analgesic effect and side effects. EEG finding was as follows. In G-I, alpha and beta waves appeared dominantly during operation. In G-II, G-III and G-IV, EEG showed specific beta wave which is characterized with low voltage and rapid activity. This specific EEG change emerged at 10 minutes after the intrathecal injection of M in G-III and G-IV, and at 60 minutes after the intrathecal injection of B in G-II. This finding showed that intrathecal M with less lipid solubility reached more rapidly to CSF in the fourth ventricle than intrathecal B. The result suggests that the earlier respiratory depression may be caused by large doses of intrathecal M. Postoperative analgesic effect was recognized remarkably in G-II, G-III and G-IV (P less than 0.01). The duration for pain relief was 6 hrs in G-II and 12 hrs in G-III and G-IV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2194054 TI - [Clinical evaluation of sulbactam/cefoperazone in lower respiratory tract infections]. AB - Clinical evaluation, safety and kinetics in serum of sulbactam/cefoperazone (SBT/CPZ) in patients with lower respiratory tract infections have been studied in a multicenter trial participated by 28 institutions in Kyushu area during a period of 13 months from March 1987 to March 1988. 1. Mean peak serum levels of SBT and CPZ in 35 patients up to 4 hours after intravenous infusion of 2 g of SBT/CPZ were 38.2 +/- 17.3 micrograms/ml for SBT and 104.3 +/- 31.4 micrograms/ml for CPZ. Serum half-lives of SBT and CPZ were 0.76 hour and 1.53 hours, respectively. These results were in similar ranges to those reported elsewhere for SBT/CPZ. 2. Serum half-lives of SBT and CPZ after intravenous infusion of 2 g of SBT/CPZ were not significantly prolonged in patients with moderate liver or kidney dysfunctions. 3. Clinical efficacy rates of SBT/CPZ in 217 patients were 93.1% (81/87) for pneumonia, 93.3% (14/15) for lung abscess, 78.9% (15/19) for acute exacerbation of chronic bronchitis, 57.1% (4/7) for diffuse panbronchiolitis, 72.4% (21/29), 74.4% (32/43) and 100% (9/9) for infections concurrent to bronchiectasis, chronic respiratory disease and pulmonary emphysema, respectively. Those were 50% (1/2) for bronchitis associated with lung cancer and 66.7% (4/6) for empyema. The overall efficacy rate was 83.4% (181/217). 4. Clinical efficacy rate of SBT/CPZ for pneumonia in patients with underlying diseases such as lung cancer, pulmonary tuberculosis and pneumoconiosis, etc, was 85.3% (29/34) and was not significantly different from the efficacy rate of 98.1% (52/53) in patients without these underlying diseases. 5. Of 30 patients who failed to respond of previous antibiotic treatments, 21 were effectively treated by SBT/CPZ. 6. Bacteriological eradication rates against Pseudomonas aeruginosa, Haemophilus influenzae and Streptococcus pneumoniae were 42.9% (9/21), 87.5% (14/16) and 100% (5/5), respectively. The overall eradication rate in all cases including polymicrobial infections was 72.8% (67/92). 7. The high levels of peak serum concentration of CPZ, and the difference between serum levels of SBT and of CPZ seemed to contribute to the high clinical efficacy. 8. Adverse reactions occurred in 2.8% (6/217) of the patients, and consisted primarily of rash and diarrhea. Laboratory abnormalities were observed in 8 patients during the study. These were elevations of S-GOT and S-GPT, and eosinophilia. 9. SBT/CPZ is a very useful drug in the treatment of lower respiratory tract infections as it has become available just in time when increase in resistant organisms to beta-lactams is notable. PMID- 2194055 TI - [Evaluation of effectiveness of rokitamycin dry syrup in acute enteritis in pediatrics. A comparative study on rokitamycin and fosfomycin dry syrups]. AB - Because Campylobacter jejuni is most frequently identified as a causative organism of bacterial enteritis in pediatrics, a study was done to evaluate the clinical efficacy against Campylobacter enteritis and the safety of a macrolide antibiotic, rokitamycin (RKM). In case of acute enteritis, RKM was used in a form of dry syrup at a dose level of approximately 30 mg (in potency)/kg body weight and its efficacy and safety were compared to those of fosfomycin (FOM) dry syrup which is currently in use at a dose level of 60 mg (in potency)/kg. Both drugs were administered, as a rule, in 3 divided daily dose (RKM before meal and FOM after meal) for 5 consecutive days. Comparisons of the drugs were made using a well-controlled method. Obtained results are summarized as follows. 1. No significant differences in background factors of the 2 drug groups were apparent, hence it was deemed that no obstacles existed in making comparative studies of the 2 groups with regard to their efficacies and safeties. 2. Overall efficacy rate against Campylobacter enteritis was 100% in the RKM group with a rate of excellent efficacy of 91.3% and the former was 94.4% in the FOM group with the latter of 72.2%. Though the RKM group apparently showed higher rates by 5.6% and 19.1%, respectively, for overall and excellent efficacies, they were not statistically significant as both drugs showed good efficacies. When acute cases of enteritis other than those caused by Campylobacter were included in the analysis, overall efficacy rates and rates of excellent efficacy were, respectively, 97.6% and 85.7% for the RKM group and 88.6% and 68.2% for the FOM group, thus RKM showed higher efficacy rates by 9.0% and 17.5%, respectively. These differences were deemed statistically significant using the U-test. 3. Numbers of days required for most of the major symptoms to subside were 3 days or less for the group for which RKM was used against Campylobacter enteritis. Similar results were observed for the FOM group also. In cases of acute enteritis due to other causes than Campylobacter, slower recoveries were observed for both the RKM and the FOM groups than in Campylobacter enteritis cases, with the latter group slower than the former. In cases of puruloid stool, the recovery in the RKM group was significantly faster by U-test than the FOM group, and a similar trend was observed overall. 4. Bacteriologically, the eradication rate of Campylobacter in the RKM group was very good at 91.3% with the FOM group showing a rate of 78.9%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2194056 TI - [Clinical evaluation of cefteram pivoxil in respiratory tract infections]. AB - The usefulness of cefteram pivoxil (CFTM-PI) was evaluated in 99 cases with respiratory tract infections: 32 cases with acute bronchitis, 51 cases with infectious exacerbations of chronic respiratory diseases and 16 cases with pneumonia. 1. The clinical efficacies included marked improvement in 27 cases, improvement in 51 cases, moderate improvement in 9 cases, no change in 10 cases and deterioration in 2 cases. The improvement rate was 78.8%. 2. Overall effects were excellent in 12 cases, good in 9 cases and fair in 5 cases. There was no case in which efficacy was not observed and the efficacy rate was 80.8%. 3. Bacteriological effects were classified according to the causative organisms. Eradication rate was 80.8% (21 of 26 strains), indicating an excellent antibacterial action of CFTM-PI. In particular, MICs of cefteram were below 0.05 microgram/ml against all 10 strains of Haemophilus influenzae regardless of beta lactamase production even with an inoculum of 10(8) or 10(6) cells/ml. 4. Side effects rarely occurred and included a slight gastrointestinal irritation in 4 of 99 cases (4%). Two cases which had abnormal elevations of GOT and GPT had abnormal values prior to administration of CFTM-PI. The elevations were slight and it was possible to continue administration. The GOT and GPT values were improved after the end of administration. The above results indicate the usefulness of CFTM-PI in acute respiratory infections and infectious exacerbation of chronic respiratory diseases. PMID- 2194057 TI - [Hospital and district differences in susceptibilities to antibiotics of main clinical isolates]. AB - A nationwide survey of susceptibilities of Staphylococcus aureus, Escherichia coli, Klebsiella sp. and Proteus mirabilis initiated in 1980 was continued in 1986. This report documents differences in susceptibilities of clinical isolates of the above microorganisms to ampicillin (ABPC), cefazolin (CEZ), cefmetazole (CMZ) and gentamicin (GM) among general hospitals throughout Japan. Clinical isolates of each species of microorganisms which were collected in 24 hospitals made up each study group and were collected at the Kosei General Hospital, Tokyo, from April 1980 to March 1986. We compared the variability in the resistant rates (MIC greater than or equal to 25 micrograms/ml) and MICs of each antibiotic for 50% and 80% of the isolates among the hospitals. MICs were determined by the serial 2 fold agar plate dilution method, standardized by the Japan Society of Chemotherapy, with an inoculum of approximately 10(6) CFU/ml or 10(8) CFU/ml. Susceptibility patterns of S. aureus to ABPC, CEZ and GM, of E. coli to ABPC, of Klebsiella sp. to CEZ and GM and of P. mirabilis to ABPC, CEZ and GM varied from hospital to hospital. On the other hand, the differences in the susceptibility patterns among the 6 districts of Japan were not obvious, because the differences were affected by different susceptibility patterns of each hospital located in each district. PMID- 2194058 TI - [Recent progress in computer assisted laboratory diagnosis for peripheral hemogram]. PMID- 2194059 TI - [Current information processing systems in our AMHTS]. PMID- 2194060 TI - Evaluating human and automated interpretation of visual field data in perimetry. AB - The complexity of visual field result evaluation has increased with the advent of automated perimetry. This in turn makes software assistance such as provided by the new Octosmart program interesting and desirable. Its accuracy and reliability in visual field evaluation must be tested, though, and the testing methodology itself must be developed. For this purpose, 27 visual fields were evaluated by three human interpreters and the Octosmart program. Based on a newly developed compound index, the performance of the three interpreters and Octosmart is described and a high degree of consistency is demonstrated. PMID- 2194061 TI - Functions of the nociceptive primary neurons. AB - The functions of nociceptive primary neurons are reviewed in brief, with special reference to the polymodal receptor. The polymodal receptor is considered to be a primitive sensory receptor that is not well differentiated and that plays important roles in signaling pain especially from tissues in pathological states, and in causing reflex modulations of a wide variety of bodily functions. This sensory receptor is characterized by the existence of neuropeptides in its neuron. The wide distribution of the central axon branchings of this neuron and the long-lasting effects of the neuropeptides released from the axon terminals provide an "analogue-like" action of the nervous system, which had hitherto been considered to be "digital-like," point-to-point connections in the central neuron network. Neuropeptides released from the peripheral endings of this neuron, on the other hand, play important roles in local regulation of such functions as inflammation, visceral tract motility, trophic effects, immune system functioning and so on. The functions of nociceptive primary neurons are, therefore, not limited to sensory function but should be understood as a component related to the regulation of fundamental functions of the entire organism. PMID- 2194062 TI - Developments in the care of 'new' long-stay inpatients in the United Kingdom- implications for Japanese psychiatry. AB - The English "ward-in-a-house" for new long-stay patients (NLS) is described. NLS are usually defined as (a) aged between 18 and 65, (b) continuously in hospital for between 1 and 5 years, and (c) individuals for whom it has not been possible to find alternative accommodation outside hospital, despite repeated attempts to do so. The "ward-in-a-house" combines the best features of high quality hospital care with the best features of community-based residential units. The "Koike dormitory" which was set up more than 20 years ago in Maebashi city had many of the characteristics of the English "ward-in-a-house" and this is also described. The possibility of developing a "ward-in-a-house" in Japan is then discussed. PMID- 2194063 TI - In memory of a special nurse. Patricia A. "Pat" Devine, R.N., M.S., F.A.A.N. June 24, 1926-April 6, 1990. PMID- 2194064 TI - Tamm-Horsfall protein--uromodulin (1950-1990). PMID- 2194065 TI - Role of precipitating and nonprecipitating antibodies in glomerular immune complex formation. AB - The present study compared directly the ability of precipitating and nonprecipitating antibodies to form and sustain glomerular immune deposits. The antigen phenylated gelatin (DNP-GL) was injected i.v. into rats. DNP-GL is cleared from the circulation rapidly and becomes localized in glomeruli. Two hours later, rats received either precipitating or nonprecipitating mouse monoclonal anti-DNP antibodies. These antibodies were comparable with respect to size, affinity, number of antigen combining sites and isoelectric point. However, in vitro, nonprecipitating antibodies demonstrated a faster dissociation rate from antigen than precipitating antibodies. Control rats received DNP-GL alone or antibody alone. Antibody deposition in glomeruli was quantitated by Computerized Image Analysis (CIA) of immunoperoxidase stained tissue sections and by glomerular radioactive counts in experiments using 125I labelled antibodies. We demonstrated that glomerular uptake of anti-DNP antibody was similar two hours after injection of precipitating and nonprecipitating antibodies. However, six or more hours after injection, significantly less antibody was present in the glomeruli of rats injected with nonprecipitating antibodies. These differences could not be explained by a greater rate of antigen removal from kidney in rats injected with nonprecipitating antibodies. To assess whether nonprecipitating antibodies modify the glomerular binding and retention of precipitating antibody, in a separate series of experiments rats were injected with equal amounts of precipitating and nonprecipitating antibodies. Both types of antibody bound to glomeruli. However, with time glomerular antibody levels paralleled those found in rats injected with nonprecipitating antibody alone. We conclude that the precipitating characteristics of antibodies do not affect their ability to deposit in kidney.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2194066 TI - Molecular cloning of a complementary DNA to rat cyclophilin-like protein mRNA. AB - Using the technique of differential plaque filter hybridization, a rat cDNA was isolated whose corresponding gene expression in the kidney was positively modulated up to threefold by sodium depletion. This mRNA was more abundantly expressed in the kidneys of 17-week-old spontaneously hypertensive rats than those of age-matched Wistar-Kyoto rats. The putative protein encoded by this cDNA is a homologue of cyclophilin, a cytosolic binding protein for cyclosporin A. This cyclophilin-like protein mRNA was expressed in all the tissues examined, including the adrenal, atrium, brain, kidney, liver, lung, spleen, and ventricle. Sodium depletion in rats increased the expression level of this mRNA not only in the kidney but also in the liver. The administration of cyclosporin A in rats increased the expression level of this mRNA in the kidneys and livers. By virtue of its possible involvement in sodium homeostasis and its homology to cyclophilin, this molecule might have significant implications in the mechanism of cyclosporine-induced renal insufficiency and hypertension. PMID- 2194067 TI - Role of endothelin in cyclosporine-induced glomerular dysfunction. AB - Since recent studies indicate that cyclosporine (CsA) disrupts endothelial integrity and that injured endothelial cells release excess endothelin, we examined endothelin's role in acute cyclosporine nephrotoxicity. Following CsA (20 mg/kg i.v.), rabbit anti-porcine endothelin (aE) serum was continuously infused into a first order branch of the main renal artery in Munich-Wistar rats whereupon the hemodynamics of glomeruli not infused with aE as well as those infused with aE within the same kidney were simultaneously assessed by micropuncture techniques. In CsA treated kidneys, in glomeruli not infused with aE, single nephron GFR (SNGFR) and glomerular plasma flow rate (QA) fell profoundly (on average by 42 and 48%, respectively) below the baseline values in association with lower glomerular capillary pressure and elevated afferent arteriolar resistance. By contrast, in glomeruli infused with aE within the same CsA treated kidneys, this vasoconstrictive pattern was markedly attenuated: SNGFR was, on average, only 19% lower than baseline and values for QA as well as other parameters determining glomerular filtration were at or near the levels observed before administration of CsA. In another group of rats (N = 6) an identical dose of CsA was given to measure the circulating level of endothelin. In these CsA treated rats, endothelin level (measured by radioimmunoassay) was elevated at 41.7 +/- 14.7 pg/ml, contrasting the value of less than 2 pg/ml uniformly observed in identically instrumented normal rats not given CsA (N = 5). Thus, cyclosporine is a potential inducer for endothelin release and endothelin appears to have a pivotal role in pathophysiology of cyclosporine-induced acute renal vasoconstriction and glomerular dysfunction. PMID- 2194068 TI - Effects of high concentrations of glucose on PTH secretion in parathyroid cells. AB - We examined the effects of high concentrations of glucose on PTH secretion from cultured bovine parathyroid cells. Increasing medium concentration of glucose caused suppression of PTH secretion. A significant suppression of PTH secretion was found within 48 hours of incubation with as little as 15 mM glucose. The addition of choline chloride to the medium did not suppress PTH secretion, although the osmolality was the same as that of the medium containing 50 mM glucose. When cells previously exposed to 50 mM glucose were reincubated in the medium containing 5 mM glucose for another 48 hours, a complete recovery of PTH secretion was observed. In the cells exposed to 50 mM glucose, the magnitude of the response of PTH secretion to 10(-6) M isoproterenol was blunted. Acid-urea gel electrophoresis revealed that the pattern of intact PTH and fragments secreted from cells exposed to high concentration of glucose was similar to that from control cells. Removal of insulin from the medium resulted in a suppression of PTH secretion similar to changes observed with high concentrations of glucose. The suppressive effects of high concentrations of glucose and lack of insulin were additive. However, we cannot exclude from the present studies whether the suppressive effects of the lack of insulin on PTH secretion was secondary to the fact that insulin may be required for the maintenance of parathyroid cells. The present studies demonstrate that glucose directly modulates PTH secretion in primary parathyroid cell culture. PMID- 2194069 TI - Renal complications of human immunodeficiency virus type 1. PMID- 2194070 TI - Immunochemical characterization of a tumor-associated antigen defined by a monoclonal antibody. AB - A murine monoclonal antibody of the subclass IgG2b, designated MAb JSI, was produced utilizing standard hybridoma technology. Female BALB/c mice were immunized with a fetal antigen that had been partially purified from the spent serum-free culture media of a human melanoma cell line. Utilizing MAb JSI, the antigen was isolated from serum of melanoma patients by affinity chromatography utilizing an acid elution and studied following exposure to trypsin, protease, and heat in an enzyme-linked immunosorbent assay (ELISA). The antigenic activity was destroyed following treatment with trypsin and protease as well as by exposure to heat (100 degrees C). By immunoperoxidase staining, MAb JSI reacted with melanoma, carcinoma, and sarcoma cell lines, but not with cell lines derived from normal skin or lungs. Affinity-isolated antigen was subjected to polyacrylamide gel electrophoresis and stained with Coomassie blue. Under dissociating conditions, a band in the 31,000 to 42,700 Da range was identified that was shown to be reactive with MAb JSI in ELISA. The antigenic determinant defined by MAb JSI appears to be a protein, with expression on a number of malignant tissues. PMID- 2194071 TI - Adverse effects of cyclosporine on islet growth and differentiation. AB - In light of recent evidence that cyclosporine (CsA) inhibits growth of the exocrine pancreas, we decided to examine the effects of cyclosporine in a hamster model of islet cell proliferation and differentiation induced by partial pancreatic duct obstruction (PPDO), in which the growth of pancreatic endocrine tissue is mediated by production of an islet cell growth factor (ICGF) contained in a cytosolic extract of pancreas. In Part I of this study, extract was prepared from PPDO pancreas, from PPDO pancreas in animals treated with CsA (20 mg/kg ip daily for 10 days), and from pancreas in control animals. Data obtained from an in vivo bioassay confirmed that administration of the extract derived from PPDO and PPDO + CsA animals increased pancreatic organ weight significantly by 10 and 17%, respectively, compared to control. Similarly, total pancreatic DNA content was increased significantly by 25 and 41%, respectively. In Part II of the study, the direct effect of CsA on islet cell proliferation and differentiation induced by PPDO was examined. The number of islets per square millimeter and the uptake of tritiated thymidine by islet cells (%) were increased significantly in PPDO animals (2.4 +/- 0.1 and 0.56 +/- 0.06) compared to those in PPDO + CsA animals (1.2 +/- 0.1 and 0.24 +/- 0.01) and to those in controls (1.1 +/- 0.0 and 0.22 +/ 0.07). It is concluded from the data in Part I that CsA does not inhibit ICGF production, but the results of Part II suggest that CsA acts to block ICGF activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2194072 TI - Endotoxin-induced myocardial depression in rats: effect of ibuprofen and SDZ 64 688, a platelet activating factor receptor antagonist. AB - We tested the hypothesis that lipopolysaccharide (LPS)-induced myocardial dysfunction is mediated by cyclooxygenase-derived metabolites of arachidonic acid or platelet activating factor (PAF). Ether-anesthetized rats were injected iv with normal saline (NS; 2.5 ml/kg), ibuprofen (cyclooxygenase inhibitor; 15 mg/kg), or SDZ 64-688 (PAF receptor antagonist; 5 mg/kg). Thirty minutes later, the rats were injected iv with NS (5 ml/kg) or Escherichia coli 0111:B4 LPS (20 mg/kg). Two hours later, atria were harvested, connected to an isometric force transducer-amplifier-recorder apparatus, and maintained in vitro in oxygenated 37.5 degrees C Krebs--Henseleit buffer. Force of contraction indexed to body weight (FOCI; g/kg) was significantly (P less than 0.05) lower in the NS/LPS group (N = 7) than in the NS/NS group (N = 7). Pretreatment with ibuprofen (ibuprofen/LPS group; N = 8) did not affect the adverse effect of LPS on atrial FOCI. In contrast, pretreatment with SDZ 64-688 (64-688/LPS group; N = 8) ameliorated (P less than 0.05) the deleterious effect of LPS on contractility. The PAF antagonist did not manifest intrinsic positive inotropic activity (64 688/NS group; N = 8). These results support the notion that LPS-induced myocardial dysfunction in the rat is mediated, at least in part, by PAF. PMID- 2194073 TI - Experimental models of acute pancreatitis. AB - Acute pancreatitis remains a disease of uncertain pathogenesis and nonspecific therapy. Because of the practical problems plaguing investigation of pancreatitis in man, investigators have developed various experimental animal models of pancreatitis in order to develop rationale concepts regarding pathogenesis and therapy. Despite numerous investigations over the past century, the events involved in the initiation and progression of pancreatitis remain obscure. Indeed, identification of the cellular mechanisms responsible for the initiation of this disease may allow for significant advances in therapy. Previous studies have largely focused on the mechanism of pancreatitis at the organ level. It is now apparent that the early initiating events in acute pancreatitis probably occur at a membrane or intracellular level. The resolution of the cellular events which underlie the development of pancreatitis in combination with the introduction of new therapeutic agents may enable a rational and safe protocol to be developed for the support of patients with pancreatitis. In this review different experimental models of acute pancreatitis are discussed. Emphasis is placed on the relevance of various models to clinical pancreatitis. PMID- 2194074 TI - Biotinyl-estradiol derivatives in enzyme immunoassays: structural requirements for optimal antibody binding. AB - The use of the avidin/biotin complex in immunoassays is well documented. No comprehensive studies, however, are available on the structural requirements of the linkage between biotin and small molecules to get an optimal antigen-antibody interaction. We have synthesized seven different biotinylated estradiol derivatives. They were evaluated in an antibody- and in an antigen-immobilized enzyme immunoassay system. All three derivatives lacking a spacer group were useless for use in immunoassays, demonstrating the importance of a long distance between the biotin- and estradiol-moiety. In addition, the chemical structure of the linkage at the site of attachment to the steroid skeleton is very important for the antibody recognition: it may either be rigid but identical to that one used in the immunogen (6-carboxymethyloxime), or must be structurally flexible as exemplified by a 6-amido-linkage. A rigid structure (hydrazone) different from that of the immunogen absolutely prevents antibody binding. PMID- 2194075 TI - Reasons for reduced activities of 17 alpha-hydroxylase and C17-C20 lyase in spite of increased contents of cytochrome P-450 in mature rat testis fetally irradiated with 60Co. AB - Pregnant rats received whole body irradiation with 2.6 Gy gamma-ray from a 60Co source at Day 20 of gestation. When pups were 4 months old, activities of electron transport system and steroid monooxygenase in tests were assayed. The content of total cytochrome P-450 in the irradiated testes had increased to 170% of that in non-irradiated rats, but NADPH-cytochrome P-450 reductase activity had reduced to 36% of the control. Also, amounts of cytochrome b5 in testicular microsomal fraction were decreased markedly after irradiation, but no significant change of NADH-cytochrome b5 reductase activity was observed in the treated pups. Because both 17 alpha-hydroxylase and C17-C20 lyase activities tended to be decreased by fetal irradiation, testosterone production from progesterone and 17 alpha-hydroxyprogesterone was reduced to about 30% of the control. From these results, it has been suggested that the testicular cytochrome P-450 is radioresistant but steroid monooxygenase activities are reduced after the fetal irradiation. We propose that the discrepancy arises from the marked decrement of NADPH-cytochrome P-450 reductase activity. PMID- 2194076 TI - Polyoxygenated sterols and triterpenes: chemical structures and biological activities. AB - Cholesterol and other sterols are precursors of many hormones of vertebrates (pregnane, androstane, estrane derivatives), invertebrates (ecdysteroids) and even of plants (brassinoids). The normal biosynthetic processes which begin by a series of oxidations lead to a family of compounds, some of which exhibit a wide variety of biological activities. Among the latter, those well-established are their inhibitory effect on the biosynthesis of cholesterol in mammalian cells, their toxic effect on tumor cells and their ability to modify some immunological responses. None of the members of this family has all of the activities just mentioned. The intensity of the effect depends markedly upon the specific structure of each compound. PMID- 2194077 TI - Nuclease sensitivity of estradiol-charged estrogen receptor binding sites in nuclei isolated from normal and neoplastic rat mammary tissues. AB - The interaction of partially purified calf uterine estradiol-charged estrogen receptor ([3H]ER) with rat nuclei was studied in vitro. We previously observed a significantly greater number of [3H]ER binding sites (at saturation) in nuclei of R3230AC mammary tumors from intact vs ovariectomized (ovex) rats with no difference in the affinity of [3H]ER binding for these nuclei. We now report on the nuclease sensitivity of [3H]ER binding sites in nuclei from these tumors and from normal rat tissues. Digestion of tumor nuclei with deoxyribonuclease I (DNase I) prior to incubation with [3H]ER in vitro resulted in a progressive loss of [3H]ER binding capacity, which was not accompanied by alterations in the affinity of [3H]ER for the nuclei (Kd = 1-3 nM). A significantly lower concentration (P less than 0.005) of DNase I eliminated 50% of the [3H]ER binding sites in nuclei of tumors from intact hosts (8 unit.min/ml) compared to tumors from ovex hosts (22 unit.min/ml). These results indicate that DNA regions capable of binding ER are more susceptible to DNase I digestion in tumors from intact rats than those from ovex hosts, suggesting that the endogenous hormonal milieu is responsible, at least in part, for maintenance of nuclease-sensitive DNA conformations in this hormone-responsive mammary tumor. The amount of DNase I required to eliminate 50% of [3H]ER binding to nuclei from lactating mammary gland, liver, and kidney ranged from 14 to 56 unit.min/ml. Therefore, accessibility of [3H]ER binding sites to nuclease digestion in normal rat tissue is generally less than that of R3230AC tumors. PMID- 2194078 TI - [Medical progress enhances the risk of candidemia and disseminating candidiasis]. PMID- 2194079 TI - [Look systematically for malaria in exposed children]. PMID- 2194080 TI - [The man behind the syndrome. Arvid Afzelius. The first to recognize the key symptom in tick-transmitted borreliosis]. PMID- 2194081 TI - [HCG and ultrasonics--a diagnostic aid in extrauterine pregnancy]. PMID- 2194082 TI - [Hellmuth Hertz deceased--one of the creators of echocardiography]. PMID- 2194083 TI - [Group A streptococcal infection caused pleural empyema in children]. PMID- 2194084 TI - [Group A streptococcal septicemia in children with the skin as a frequently probable route of entrance]. PMID- 2194085 TI - [Septic arthritis of the sternoclavicular joint caused by Streptococcus group B]. PMID- 2194086 TI - [The Axel Hirsch prize to Viktor Mutt. The man of the silent hormones and the master of the peptides]. PMID- 2194087 TI - [Bellman's poetry touch the vital nerve of alcohol drinking]. PMID- 2194088 TI - The management of the divided recurrent laryngeal nerve. PMID- 2194089 TI - Leukotriene C4-induced release of LHRH into the hypophyseal portal blood and of LH into the peripheral blood. AB - Intracerebroventricular (i.c.v.) administration of leukotriene (LT) C4 at doses of 2, 0.5 and 0.2 micrograms/rat significantly stimulated (3-12 fold) the release of LH into the peripheral blood of male rats. Injection of anti-LHRH serum had no effect on LTC4-stimulated LH release, but did block PGE2- stimulated LH release. I.c.v.- infused LTC4 also stimulated the release of LHRH into the hypophyseal portal blood. This is the first report of an in vivo action of LTC4 on the release of a hypothalamic releasing factor (LHRH) and a pituitary hormone (LH). These observations, plus in vitro results, clearly show that LTC4 stimulates LH release by acting on both the hypothalamus, causing LHRH release, and on the pituitary. Then the action of LTC4 on LH release in vivo is quite different from the indirect action of PGE2. PMID- 2194090 TI - Effects of endothelin and vasopressin on portal pressure of rats. AB - Endothelin is a vasoconstrictor peptide which has recently been isolated and sequenced from the vascular endothelial cells. It was reported to increase blood pressure in vivo and produce a prolonged contraction with a slow onset in vitro. The purpose of this study was to investigate whether endothelin can lower the portal pressure as another endogenous vasoconstriction peptidevasopressin (AVP) can. Heart rate, systemic blood pressure, portal pressure, and portal vein blood flow were measured. Effects of endothelin on these parameters were compared with those of AVP. Endothelin 10(-10) mol/Kg significantly decreased all of the parameters mentioned. At the higher dose (5 x 10(-10) mol/Kg), however, the portal pressure and blood pressure were increased and portal vein blood flow was unchanged. On the other hand, AVP decreased the portal pressure and portal vein blood flow but elevated the systemic blood pressure. In vitro experiments revealed that endothelin contracted both tail artery and portal vein of rat and vasopressin contracted only tail artery. We concluded that although both are endogenous vasoconstricting peptides, endothelin and AVP affect differently on arterial and venous vascular beds as well as on portal pressure. PMID- 2194091 TI - A mathematical model of interstitial transport. I. Theory. AB - A generalized model is developed to describe the transport of fluid and plasma proteins or other macromolecules within the interstitium. To account for the effects of plasma protein exclusion and interstitial swelling, the interstitium is treated as a multiphase deformable porous medium. Fluid flow is assumed proportional to the gradient in fluid chemical potential and therefore depends not only on the local hydrostatic pressure but also on the local plasma protein concentrations through appropriate colloid osmotic pressure relationships. Plasma protein transport is assumed to occur by restricted convection, molecular diffusion, and convective dispersion. In a companion paper (D. G. Taylor, J. L. Bert, and B. D. Bowen, 1990, Microvasc. Res. 39, 279-306) a simplified version of the model is used to analyze steady-state fluid and plasma protein exchange within mesentery. PMID- 2194092 TI - A mathematical model of interstitial transport. II. Microvascular exchange in mesentery. AB - A simplified version of the model of interstitial transport developed earlier (D. G. Taylor, J. L. Bert, and B. D. Bowen, 1990, Microvasc. Res. 39, 253-278) is used to investigate microvascular exchange of fluid and a single "aggregate" plasma protein species in mesenteric tissue. The interstitium is approximated by a rigid, rectangular, porous slab displaying two fluid pathways, only one of which is available to plasma proteins. The model is used to explore the effects of the interstitial plasma protein diffusivity, the tissue hydraulic conductivity, the restricted convection of plasma proteins, and the mesothelial transport characteristics on the steady-state distribution and transport of plasma proteins and flow of fluid in the tissue. The simulations predict significant convective plasma protein transport and complex fluid flow patterns within the interstitium. These flow patterns can produce local regions of high fluid and plasma protein exchange along the mesothelium which might be erroneously identified as "leaky sites." PMID- 2194093 TI - Demonstration of RNA N-glycosidase activity of a Vero toxin (VT2 variant) produced by Escherichia coli O91:H21 from a patient with the hemolytic uremic syndrome. AB - A new Vero toxin purified from Escherichia coli O91:H21 isolated from a patient with the hemolytic uremic syndrome (VT2vh) was shown to inhibit elongation factor 1-dependent aminoacyl-tRNA binding to ribosomes, resulting in inhibition of protein synthesis in rabbit reticulocytes. VT2vh, like Shiga toxin, VT1 and VT2, showed RNA N-glycosidase activity and cleaved the N-glycosidic bond of the adenosine residue at position 4324 in 28S ribosomal RNA. PMID- 2194096 TI - Brain protection. PMID- 2194097 TI - Hemodynamic changes during liver transplantation in adults and children. PMID- 2194098 TI - How to set the ventilator in acute respiratory failure. PMID- 2194099 TI - Does surfactant play a role in acute respiratory failure? PMID- 2194095 TI - Codon preferences in free-living microorganisms. AB - A popular interpretation of the major codon preference is that it reflects the operation of a regulatory device that controls the expression of individual proteins. In this popular model, rapidly translated codons are thought to promote the accumulation of the highly expressed proteins and slowly translated codons are thought to retard the expression of poorly expressed proteins. However, this widely accepted model is not supported by kinetic theory or by experimental results. A less fashionable model in which the major codon preference has nothing to do with the expression level of the individual proteins is forwarded. In this model, the major codon preference is viewed as a global strategy to support the efficient function of the translation system and thereby to maximize the growth rates of cells under favorable conditions. PMID- 2194100 TI - Treatment of cyanide poisoning with 4-dimethylaminophenol (DMAP)--experimental and clinical overview. PMID- 2194101 TI - Spinal opiates. PMID- 2194102 TI - Use of scoring systems to evaluate prognosis and outcome of critical patients. PMID- 2194103 TI - Dr. Anis Shehat Baraka. PMID- 2194104 TI - Mutations in conserved domains of U14 RNA impair 18S ribosomal RNA production in Saccharomyces cerevisiae. PMID- 2194105 TI - Mutations define essential and nonessential U2 RNA structures. PMID- 2194106 TI - Point mutations in yeast U6 snRNA can specifically block the first or second step of pre-mRNA splicing in vitro. PMID- 2194107 TI - Transcription of the human U2 and U6 RNA genes. PMID- 2194108 TI - Structural basis of tRNA discrimination as derived from the high resolution crystal structure of glutaminyl-tRNA synthetase complexed with tRNA(Gln) and ATP. PMID- 2194109 TI - Structure and function of La and Ro RNPs. PMID- 2194110 TI - Characterization of messenger ribonucleoprotein particles. PMID- 2194111 TI - Cytoplasmic mRNP proteins affect mRNA translation. PMID- 2194113 TI - [The role of histocompatibility antigens in nonimmune intercellular interactions]. PMID- 2194114 TI - [Local amplification of nucleic acids--a new method of analysis]. PMID- 2194112 TI - New RNPs of higher eukaryotes. PMID- 2194115 TI - [Cloning and regulation of gene expression of EcoRV restriction- modification system]. AB - A number of recombinant plasmids, containing EcoRV restriction-modification genes have been constructed. Individual genes of this system were introduced into plasmids of various incompatibility groups. Promoter regions of genes encoding methylase and restrictase have been cloned and studied. With the use of specialized vector pVE8 it was shown that the efficiency of the endonuclease gene promoter is comparable with early lambda phage promoters and produced about 70% of PL efficiency. The efficiency of the methylase gene promoter region was twice less than the efficiency of the restriction endonuclease gene promoter. Plasmid with restriction endonuclease gene promoter located downstream in relation to the additional regulatable phage lambda promoter PL has been obtained. It enabled us to construct strains 30-40 fold overproducing this enzyme under conditions of inactivation of the temperature sensitive phage repressor c1857. This construction directs the production of a high level (10%) of the total cellular soluble proteins) of the EcoRV restriction enzyme. The factors that influenced the level of enzyme synthesis under induction are discussed. PMID- 2194116 TI - [Study of the mechanism of mutagenesis directed by phosphotriester analogs of oligonucleotides. The role of repair in mutagenesis]. AB - The mutation system has been suggested in an effort to test insertion and deletion mutants by changing the Lac-phenotype of bacterial colonies transformed by mutant DNA. This system also makes possible to determine heterozygotes and homozygotes among the mutants. The yield of mutants in shown to depend on the structure of the DNA heteroduplex region. The yield of deletion mutants is greater than that of insertion mutants. Heterozygotes prevail in mutant colonies (greater than 90%). PMID- 2194117 TI - [Structural-functional organization of the par region of the ColN plasmid]. AB - In the 679 b.p. SalI-KpnI-fragment of the small colicinogenic plasmid Co1N, the par-region has been localized, functioning at the expense of resolution of plasmid DNA multimer forms. It has been shown that the replication process of the monomeric form of the recombinant plasmid containing the Co1N par-region do not result in formation of a considerable number of multimers. Gene xer A product is necessary for the functioning of the multimer resolution mechanism of Co1N as well as Co1E1. Nucleotide sequence analysis of the Co1N par-region revealed the presence of essential homology with the par-locus of plasmid Co1E1. Results obtained in this work and data from literature indicate that par-regions of the Co1E1-type plasmids possess considerable homology, function according to a similar mechanism and represent the universal stability module of multicopy colicinogenic plasmids. PMID- 2194118 TI - [Possible role of malonic dialdehyde in the regulation of cell division]. AB - Malonic dialdehyde (MDA) crosslinking of complementary chains of DNA is suggested. It contributes to the stabilization of the DNA helix, making its replication impossible. MDA is considered as a cell division inhibitor. The MDA producing process (lipid peroxidation) is considered to be a normal strictly controlled in vivo process. Control of rest and proliferation alternations in normal cells and its impairment in transformed cells are discussed in terms of the proposed idea. PMID- 2194119 TI - [Genetic basis for construction of the life influenza type A vaccine using temperature-sensitive mutants]. AB - Published data and authors' original material on the use of temperaturesensitive influenza virus mutants (ts) as donors in attenuation process aimed at obtaining the recombinant live influenza vaccines (LIV) are reviewed. The so called cold adapted ts donors are shown to be superior for this aim. The data are presented in the review on the association of the mutations in the genome of cold adapted donors with attenuation, on the reactivity, immunogenicity and genetical stability of the recombinant LIVs constructed on the basis of the cold adapted donors. PMID- 2194120 TI - [A new site-specific endodeoxyribonuclease EcoHI]. AB - A new sitespecific endonuclease of the II class EcoHI has been isolated from Escherichia coli strain and characterized. Restriction endonuclease EcoHI recognises the nucleotide sequence C C (C/G) G G with the cleavage site between the fourth and fifth nucleotide. It is an isoshizomer of the restriction endonuclease CauII. The yield of enzyme is 2500 units of activity per 1 g of biomass. The producing strain Escherichia coli HI is nonpathogenic, easily grown with the antibiotic resistance markers permitting to cultivate the strain under selective conditions. PMID- 2194121 TI - Leishmania mexicana mexicana gp63 is a site-specific neutral endopeptidase. AB - Leishmania mexicana, like other species of the genus, has a major 63-kDa surface glycoprotein (gp63) that is an active protease. Reports differ as to whether gp63 is a neutral or an acidic protease. Using three radiolabeled synthetic peptide substrates, gp63 purified from L. m. mexicana is most active at pH 6.5-7.5, in three different buffer systems, and appears to be a sequence-specific endopeptidase. The full extent of sequence specificity is undetermined, but these experiments suggest a strong preference for cleavage at serine or threonine residues. In common with other metalloproteases, the cleavage is on the amino side of the recognition residue. PMID- 2194122 TI - Falciparum malaria parasitized erythrocytes bind to a carboxy-terminal thrombospondin fragment and not the amino-terminal heparin-binding region. AB - We investigated Plasmodium falciparum parasitized erythrocyte binding to proteolytic fragments of thrombospondin and the effects of anti-thrombospondin monoclonal antibodies on this binding. Purified human platelet thrombospondin was cleaved by trypsin, chymotrypsin or thrombin. Fragments were separated by heparin agarose affinity chromatography, removing the amino-terminal heparin-binding region. Trypsin at 5.0 micrograms ml-1 of thrombospondin cleaved thrombospondin to reduced 140 and 120 kDa fragments plus a reduced 25-kDa heparin-binding fragment. Infected erythrocytes bound to intact thrombospondin (3420 +/- 460 infected erythrocytes mm-2) and the carboxy-terminal fragment, yielding 120-140 kDa fragments on sulfhydryl reduction, but not to the 25-kDa fragment (144 +/- 104 infected erythrocytes mm-2 (mean +/- s.d., N = 4). Similar results were obtained with chymotrypsin and thrombin cleavage. When the anti-thrombospondin monoclonal antibody MA-I was added to immobilized thrombospondin prior to infected erythrocytes, adherence was inhibited by 99%. At the same concentration, MA-I inhibited adherence to C32 melanoma cells by only 35%. MA-I binds to a calcium-dependent structure at the C-terminal globular region of thrombospondin. Monoclonal antibody MA-II inhibited adherence to thrombospondin by 46%, while MA III had no effect. These antibodies bind to the N-terminal globular region which includes the heparin-binding site and the segment connecting the two globular regions, respectively. The site(s) for infected erythrocyte binding on thrombospondin reside in the large, 140- or 120-kDa, proteolytic cleavage fragments, and not in the N-terminal heparin-binding region. PMID- 2194123 TI - Characterization of a myosin-like antigen from Onchocerca volvulus. AB - Recombinant cDNAs expressing an immunodominant antigen (Onchoag-1) of Onchocerca volvulus were identified by immunoscreening a cDNA expression library. The Onchoag-1 cDNAs are derived from an 8-kb mRNA that codes for a protein with an apparent molecular mass of 200 kDa. Indirect immunofluorescence using antisera against a recombinant fusion protein showed that Onchoag-1 is located in the muscle tissues of adult O. volvulus. The 2-kb sequence of one of the cDNAs contains a single open translation reading frame that encodes a protein with sequence similarities to Caenorhabditis elegans myosin heavy chain. Analysis of the 3' region of Onchoag-1 chromosomal gene reveals that it is frequently interrupted by short introns that follow the GT/AG rule at their splice sites. Studies on this myofibrillar antigen should contribute to our understanding of muscle function in O. volvulus as well as provide useful insight to the genesis of the immunopathological damage that is often associated with allergic reactions (the Mazzotti reactions) in onchocerciasis patients, following the administration of a chemotherapeutic agent such as diethylcarbamazine. PMID- 2194124 TI - Water and urea transport in human erythrocytes infected with the malaria parasite Plasmodium falciparum. AB - The permeability properties of the human red cell membrane to various solutes are altered by malarial infection. In the present work we show that the permeability of the red cell membrane to water is also affected by the intraerythrocytic growth of the malaria parasite Plasmodium falciparum, whereas urea permeability appears unchanged. The data from infected cells show decreases in membrane surface area, cell volume, the osmotically active water fraction (Weff), and osmotic water permeability (Pf) as measured by stopped-flow spectroscopy. On the other hand, the data suggest an increase in diffusive water permeability (Pd) in infected cells with no change in urea permeability when measured by the continuous flow method. The decreased Pf/Pd ratio of infected cell membranes and its implications in the geometry of the red cell membrane water channel or pore are discussed. PMID- 2194125 TI - Characterization of the 175-kilodalton erythrocyte binding antigen of Plasmodium falciparum. AB - EBA-175 is a soluble 175-kDa Plasmodium falciparum antigen that is released into culture supernatants during rupture of schizont-infected erythrocytes. EBA-175 binds to erythrocytes and binding is sialic acid-dependent. A clone expressing the gene encoding EBA-175 was obtained previously by screening a genomic DNA expression library with antibodies that had been affinity-purified from EBA-175. Antibodies were raised against a 43-amino-acid peptide (EBA-peptide 4) synthesized according to the deduced amino acid sequence. Antibodies to peptide 4 and affinity-purified antibodies specific for EBA-175 were used to characterize further EBA-175 giving the following results: (1) EBA-175 differs biochemically and immunologically from other reported malarial antigens; (2) the EBA-175s from six geographical isolates of P. falciparum are antigenically conserved; (3) EBA 175 is expressed during schizogony as a 190-kDa protein which is larger than the culture supernatant form of the antigen. The 190-kDa form of the protein is recovered from the cell pellet in schizont-infected erythrocytes and partitions to the soluble fraction when extracted with detergent; (4) release of soluble EBA 175 into the culture supernatant coincides with schizont rupture; (5) there was no observable change in pI (pI = 6.86) by isoelectric focusing between the cellular and supernatant species of the protein; and (6) release of EBA-175 into the culture supernatant is inhibited by the addition of chymostatin and leupeptin. The continued research into the role of EBA-175 during erythrocyte invasion may aid in vaccine development for malaria. PMID- 2194126 TI - The effect of warfarin on mortality and reinfarction after myocardial infarction. AB - BACKGROUND AND METHODS: The use of oral anticoagulation in the long-term treatment of survivors of acute myocardial infarction has been highly controversial. We therefore randomly assigned 1214 patients who had recovered from acute myocardial infarction (mean interval from the onset of symptoms to randomization, 27 days) to treatment with warfarin (607 patients) or placebo (607 patients) for an average of 37 months (range, 24 to 63). RESULTS: At the end of the treatment period, there had been 123 deaths in the placebo group and 94 in the warfarin group--a reduction in risk of 24 percent (95 percent confidence interval, 4 to 44 percent; P = 0.027). A total of 124 patients in the placebo group had reinfarctions, as compared with 82 in the warfarin group--a reduction of 34 percent (95 percent confidence interval, 19 to 54 percent; P = 0.0007). Furthermore, we observed a reduction of 55 percent (95 percent confidence interval, 30 to 77 percent) in the number of total cerebrovascular accidents in the warfarin group as compared with the placebo group (44 vs. 20; P = 0.0015). Serious bleeding was noted in 0.6 percent of the warfarin-treated patients per year. CONCLUSIONS: Long-term therapy with warfarin has an important beneficial effect after myocardial infarction and can be recommended in the treatment of patients who survive the acute phase. PMID- 2194127 TI - Immunohistologic abnormalities of the microfibrillar-fiber system in the Marfan syndrome. AB - BACKGROUND: Indirect-immunofluorescence studies of skin and cultured dermal fibroblasts from patients with the Marfan syndrome demonstrate apparent deficiency of one element of connective tissue--the microfibrillar-fiber system- in assays using specific antibodies against fibrillin, a major microfibrillar protein. This study was designed to test whether these immunostaining abnormalities are consistent and diagnostic features of the disease. METHODS: We studied patients with either the Marfan syndrome or various other inherited connective-tissue disorders and normal subjects according to a single-blind protocol in which coded samples of skin, fibroblast cultures, or both were analyzed without knowledge of the clinical diagnosis and classified as "Marfan" or "non-Marfan" before the sample codes were broken. RESULTS: Of the 27 patients with the Marfan syndrome, 24 were correctly identified by the decreased content of microfibrillar fibers in their skin, cultured fibroblasts, or both; in contrast, 19 of 25 patients with other heritable disorders of connective tissue and all 13 normal subjects were correctly classified as "non-Marfan" by these assays (P less than 0.001). CONCLUSIONS: These results document consistent, relatively specific abnormalities of microfibrillar fibers in the Marfan syndrome. The biomechanical incompetence of these structural elements, due to quantitative or qualitative abnormalities, may account for the pleiotropic clinical manifestations of the disease. Therefore, various defects in the expression, structure, assembly, or degradation of the constituent structural glycoprotein (or glycoproteins) of microfibrils may be implicated in the causation of the Marfan syndrome. PMID- 2194128 TI - A randomized, controlled trial of vitamin A in children with severe measles. AB - BACKGROUND: Measles kills about 2 million children annually, and there is no specific therapy for the disease. It has been suggested that vitamin A may be of benefit in the treatment of measles. METHODS: We conducted a randomized, double blind trial involving 189 children who were hospitalized at a regional center in South Africa because of measles complicated by pneumonia, diarrhea, or croup. The children (median age, 10 months) were assigned to receive either vitamin A (total dose, 400,000 IU of retinyl palmitate, given orally; n = 92) or placebo (n = 97), beginning within five days of the onset of the rash. At base line, the characteristics of the two groups were similar. RESULTS: Although clinically apparent vitamin A deficiency is rare in this population, the children's serum retinol levels were markedly depressed (mean [+/- SEM], 0.405 +/- 0.021 mumols per liter [11.6 +/- 0.6 micrograms per deciliter]), and 92 percent of them had hyporetinemia (serum retinol level less than 0.7 mumols per liter [20 micrograms per deciliter]). Serum concentrations of retinol-binding protein (mean, 30.1 +/- 2.0 mg per liter) and albumin (mean, 33.4 +/- 0.5 g per liter) were also low. As compared with the placebo group, the children who received vitamin A recovered more rapidly from pneumonia (mean, 6.3 vs. 12.4 days, respectively; P less than 0.001) and diarrhea (mean, 5.6 vs. 8.5 days; P less than 0.001), had less croup (13 vs. 27 cases; P = 0.03), and spent fewer days in the hospital (mean, 10.6 vs. 14.8 days; P = 0.01). Of the 12 children who died, 10 were among those given placebo (P = 0.05). For the group treated with vitamin A, the risk of death or a major complication during the hospital stay was half that of the control group (relative risk, 0.51; 95 percent confidence interval, 0.35 to 0.74). CONCLUSIONS: Treatment with vitamin A reduces morbidity and mortality in measles, and all children with severe measles should be given vitamin A supplements, whether or not they are thought to have a nutritional deficiency. PMID- 2194129 TI - Echocardiography (2) PMID- 2194131 TI - The public and the emerging debate over national health insurance. PMID- 2194130 TI - Designer and catalytic antibodies. PMID- 2194132 TI - Destructive spondyloarthropathy in dialysis patients: an overview. AB - Destructive spondyloarthropathy has been increasingly recognized in dialysis patients. We have reviewed 39 observations published in the literature and added 11 personal cases in order to define the clinical and radiological presentation of the disease. The many hypotheses that have been proposed for its pathogenesis are discussed, including secondary hyperparathyroidism, microcrystal deposition, beta 2-microglobulin-associated amyloidosis and aluminum intoxication. PMID- 2194133 TI - Influence of thymopentin on antibody response, and monocyte and T cell function in hemodialysis patients who fail to respond to hepatitis B vaccination. AB - We investigated the influence of thymopentin as an adjuvant for hepatitis B vaccination on in vitro monocyte and T cell function and in vivo antibody response in a prospective, placebo-controlled double-blind trial in 20 low- and nonresponders to hepatitis B vaccination on chronic hemodialysis. 50 mg thymopentin was given subcutaneously twice per week for 3 weeks, followed by 1 intramuscular injection of 40 micrograms HB-Vax and 3 subsequent injections of thymopentin. After 1 month, the patients were boostered with 40 micrograms HB Vax. There was no significant difference in T cell and monocyte function after administration of thymopentin, as determined in vitro. After 3 months, 3 patients in the placebo and 2 patients in the thymopentin group had antibody titers greater than 10 U/l. In both groups only patients with normal or slightly impaired monocyte function responded to vaccination. Thus, we were not able to demonstrate a beneficial effect of thymopentin on hepatitis B vaccination in nonresponders on chronic hemodialysis. Furthermore, functional tests were not able to identify a subpopulation of uremic nonresponders who would benefit from thymopentin. PMID- 2194134 TI - Torasemide, a new loop diuretic, in patients with chronic renal failure. AB - Torasemide, a new loop diuretic, was administered in 9 hospitalized patients with chronic renal failure to treat both arterial hypertension and peripheral edema. The urine of 5 patients was collected over 12-hour periods to assess the long lasting diuretic activity of torasemide. Torasemide induced a significant decrease in blood pressure and reversion of peripheral edema in all patients without adverse effects. Torasemide is a high-ceiling loop diuretic, useful in correcting extracellular fluid volume expansion in patients with chronic renal failure. PMID- 2194135 TI - The crush syndrome revisited (1940-1990). AB - This article reviews the local and systemic effects of crush injury. Within minutes to hours after extrication of survivors trapped under fallen masonry (and immediately following decompression of limbs), a massive volume of extracellular fluid is lost into the injured muscles, leading to circulatory failure. Solutes leaking out of damaged muscles cause a spectrum of metabolic disturbances. Chief among them are hyperkalemia and hypocalcemia which, synergistically, have a lethal cardiotoxic potential, particularly in hypotensive patients. Early volume replacement, preferably already started at the rescue site, may combat shock and correct the hyperkalemia. If urine flow is established, this regimen should be followed by a forced solute-alkaline diuresis for the prevention of myoglobinuric and uricosuric acute renal failure, which is a common and ominous late complication of crush injury. Preparation for future catastrophes occurring particularly in remote regions where an 'epidemic' of crush syndrome may be forecast, should include the setting up of a radio communications network to coordinate rescue and salvage operations and the forwarding of intravenous fluid bags and lines to the disaster site. Also, it is advisable to prepare artificial kidney devices which do not require pumps and electricity and which utilize a low dialysate volume for emergency temporary use, until conventional definitive medical facilities and services have been reestablished. PMID- 2194137 TI - Skull trepanation among the early Indians of Canada and the United States. AB - The authors reviewed anthropological reports of skull trepanation (trephination) among the early Indians of Canada and the United States of America. Published reports of 20 trepanations in 19 skulls are reviewed. All were believed to have been performed ante mortem. Most were from the pre-Columbian era. Eleven were from Canada (8 from British Columbia) and 8 from the United States. The location of skull perforation was parietal in 9 cases and less often frontal (3) or occipital (3). The average skull opening was oval or oblong, with a diameter of 3.0 cm. The method of trepanation was probably gradual scraping in most cases. Skull fractures were not present in any case. About 90% of the trepanations showed evidence of healing, indicating survival. The authors discuss the evidence for skull trepanation in the United States and Canada, and compare these findings to the better studied South and Central American material. PMID- 2194136 TI - Loss of LH-RH neurons in the rostral forebrain of old female C57BL/6J mice. AB - This study reports the quantitative immunohistochemical distribution of luteinizing hormone-releasing hormone (LH-RH) neurons within the rostral forebrain of young (5-6 month) and old (26-28 month) C57BL/6J mouse. Old mice demonstrated a significant (18%) loss of LH-RH-containing neurons (p less than 0.001, ANOVA). The most striking losses involved the preoptic area (24%) and more rostral regions (26%). The presence of pituitary or mesenteric tumors in older mice did not affect the density of LH-RH neurons. These observations indicate that LH-RH neurons comprise part of the neuronal population previously reported to be reduced in the preoptic area of older mice (4). PMID- 2194138 TI - An unusual cause for trigeminal neuralgia: contralateral meningioma of the posterior fossa. AB - Twenty cases of facial neuralgia associated with tumors of the contralateral posterior fossa were collected from the world literature. Only four of these conform to the description of typical trigeminal neuralgia. We report on a fifth such case with a critical review of the literature. Subtotal excision of the tumor improves the pain and may convert a carbamazepine-resistant neuralgia into a responsive one. Total excision is often followed by a cure. Faced with such a case, the tumor should always be excised first, as this usually cures the neuralgia. Surgical treatment of the neuralgia in the presence of the tumor may be followed by disastrous results. An alternative hypothesis to the pathogenesis of the contralateral neuralgia is presented. PMID- 2194094 TI - Linkage map of Escherichia coli K-12, edition 8. AB - The linkage map of Escherichia coli K-12 depicts the arrangement of genes on the circular chromosome of this organism. The basic units of the map are minutes, determined by the time-of-entry of markers from Hfr into F- strains in interrupted-conjugation experiments. The time-of-entry distances have been refined over the years by determination of the frequency of cotransduction of loci in transduction experiments utilizing bacteriophage P1, which transduces segments of DNA approximately 2 min in length. In recent years, the relative positions of many genes have been determined even more precisely by physical techniques, including the mapping of restriction fragments and the sequencing of many small regions of the chromosome. On the whole, the agreement between results obtained by genetic and physical methods has been remarkably good considering the different levels of accuracy to be expected of the methods used. There are now few regions of the map whose length is still in some doubt. In some regions, genetic experiments utilizing different mutant strains give different map distances. In other regions, the genetic markers available have not been close enough to give accurate cotransduction data. The chromosome is now known to contain several inserted elements apparently derived from lambdoid phages and other sources. The nature of the region in which the termination of replication of the chromosome occurs is now known to be much more complex than the picture given in the previous map. The present map is based upon the published literature through June of 1988. There are now 1,403 loci placed on the linkage group, which may represent between one-third and one-half of the genes in this organism. PMID- 2194139 TI - Ganglioglioma of the optic chiasm: case report and review of the literature. AB - We describe a case of ganglioglioma of the optic chiasm and tract in a 33-year old man. Review of the literature discloses only seven cases of tumors of the anterior visual pathway that meet the histological criteria for such neoplasms. A detailed histological description of our case and a review of the literature is provided. PMID- 2194140 TI - Intraventricular neurocytoma: a clinical and pathological study of three cases and review of the literature. AB - Three patients with a recently described tumor of neuronal origin, intraventricular neurocytoma, are presented. These tumors occur as intraventricular lesions in young patients, and the prognosis after surgical treatment is favorable. The initial pathological diagnosis of intraventricular neurocytoma may be difficult because of the striking resemblance of these tumors to oligodendroglioma and, to a lesser extent, ependymoma on light microscopic examination. Despite the use of wide-ranging panels of monoclonal antibodies, previous authors have not found any characteristic immunohistochemical staining patterns, but in our three patients, the use of synaptophysin, glial fibrillary acidic protein, and Leu-7 demonstrated staining patterns that may be useful in the diagnosis of this tumor. The monoclonal antibody Ki-67 was used to stain one tumor and showed a low cell proliferation rate. We have reviewed the clinical, radiological, and pathological features of these 3 patients and 17 previously described patients in an attempt to determine the important diagnostic features of intraventricular neurocytoma. Intraventricular neurocytoma should be considered in any young patient with symptoms of raised intracranial pressure and radiological evidence of an intraventricular lesion. Pathological diagnosis requires the use of electron microscopy to show features of neuronal differentiation; however, immunohistochemical demonstration of a neuronal phenotype is also a useful adjunct to diagnosis. Failure to use specialized techniques for pathological diagnosis will lead to misdiagnosis of these lesions as oligodendrogliomas, as was the initial diagnosis in 2 of our patients before review. PMID- 2194141 TI - Calcified metastatic brain tumor. AB - The case of a 57-year-old woman with a calcified metastatic brain tumor, histologically confirmed to be a squamous cell carcinoma, is reported. This patient is unusual because this metastatic squamous cell carcinoma contained an extraordinary huge conglomerated calcification, that was well-defined radiographically. This case is documented with a discussion of the pathogenesis of the calcification. PMID- 2194144 TI - [Esthetics and function in the complete denture]. PMID- 2194142 TI - The role of gender identity and gender constancy in sex-differentiated development. PMID- 2194143 TI - Caring for the diabetic patient who takes insulin. PMID- 2194146 TI - Argon laser suturotomy: a technique for the correction of surgically induced astigmatism. AB - We prospectively studied 40 eyes with intraocular lenses and astigmatism of 4 or more diopters to evaluate the efficacy and safety of argon laser suture ablation as contrasted with surgical suture removal. Two groups of 10 eyes underwent argon laser suturotomy (ALS) 4 and 6 weeks, respectively, after surgery. Sutures were removed surgically in a third group of 10 eyes 6 weeks after surgery. The final group of 10 eyes served as controls. Serial keratometry and refraction demonstrated that ALS was as effective as surgical suture removal in reducing postoperative astigmatism, and complications associated with the procedure were negligible. PMID- 2194145 TI - Ciliary sulcus suturing of a posterior chamber intraocular lens. AB - We describe a method for ciliary sulcus fixation of a posterior chamber intraocular lens (PC-IOL) in the absence of an intact posterior capsule. This method, which combines a lens fixation procedure with trans pars plana vitrectomy techniques to ensure safe manipulation of the lens implant in the absence of an intact anterior hyaloid face, is ideally suited for retrieval and repositioning of PC-IOLs dislocated into the vitreous. It also permits closed system repositioning and fixation of the implant, thereby avoiding the complications of vitreous loss and the need for reopening the limbal incision. PMID- 2194148 TI - Posterior chamber lens placement. PMID- 2194147 TI - The Nylon Suture Lens. PMID- 2194149 TI - [Cytochemical, immunologic and gene rearrangement studies in adult acute leukemia]. AB - Results of morphological, cytochemical and immunological studies performed in adult acute leukaemias have been compared. Thirty one cases proved to be acute myeloid leukaemia, while 25 cases were shown to be acute lymphoid leukaemia. Based on our results we conclude that immunophenotyping with monoclonal antibodies does not help in distinguishing the subtypes of AML. For purposes of clinical diagnosis cytochemical methods are valuable. On the other hand the monoclonal antibodies are essential in distinguishing the very immature myeloid and lymphoid leukaemias and this is of great importance from the clinical point of view, in determining therapy. Moreover, the diagnosis of acute lymphoid leukaemias is not possible without the specific monoclonal antibodies. Their application is first of all in haematological centers caring for leukaemia patients nowadays already obligatory. Gene rearrangement studies make the diagnosis more accurate and help in the diagnosis of leukaemias of unknown immunological origin. PMID- 2194150 TI - [Management of injuries of the artificial esophagus]. AB - The authors analyse their experiences in connection with 20 cases of artificial esophageal injuries. Attention is called to the intraoperative lesions of the esophageal wall and to the damages caused by drugs. They underline the importance of the time factor and good results were achieved by using so called "conservative surgical treatment". PMID- 2194151 TI - [Prevention of acute renal failure in rhabdomyolysis caused by alcohol and drug intoxication]. AB - Authors report a case of rhabdomyolysis occurring in a chronic alcoholic patient where they suspect in the development of rhabdomyolysis beside the effect of alcohol also a role of drug intoxication and muscle compression. They found sustained myoglobinaemia and myoglobinuria, while in this case beside the hypocalcemia during the initial phase of rhabdomyolysis normal parathyroid hormone level was found. Therefore in alcoholic intoxicated patients the measurement of creatine kinase is indicated. Beside total lactate dehydrogenase the determination of isoenzymes is in some cases helpful. In the presented case despite extensive rhabdomyolysis, acute renal failure was prevented by early volumen replacement therapy and use mannitol-sodium bicarbonate infusions. Authors discuss the possibility of the role of calcium blocking agent nifedipine in the prevention of rhabdomyolysis and acute renal failure. PMID- 2194152 TI - Sexual development in malarial parasites: gametocyte production, fertility and infectivity to the mosquito vector. AB - Using cloned lines of Plasmodium berghei producing mixed asexual and sexual (clone 234L) and purely asexual (clone 233L) parasitaemias, the courses of parasitaemia, gametocytogenesis, exflagellation, ookinete production in vitro and mosquito infectivity have been followed. For clone 234L mosquito infectivity is maximal at day 3 and has ceased by day 6 post-infection. Conversely, gametocytogenesis, exflagellation and ookinete production are at minimal levels at day 3 and rise to peaks between days 10 and 15 of infection (in TO mice infected with blood at mechanical blood passage 3). Sexual potential declines progressively with sustained mechanical passage (up to P14). Gametocyte conversion is highest early in infection and declines exponentially; however, upon each mechanical passage conversion is again raised but decreases more rapidly with succeeding passages. For practical mosquito transmission in the laboratory we consider P8 to be the useful limit for mechanical transmission for this parasite clone. Asexual parasite growth (virulence) is more rapid with increased mechanical passage inducing a rapid fall in haematocrit. By P14 the course of infection closely parallels that of the purely asexual clone 233L. PMID- 2194153 TI - The prevalence of naturally acquired multiple infections of Wuchereria bancrofti and human malarias in anophelines. AB - Malaria and filaria infection rates were determined for anopheline mosquitoes collected whilst biting and resting in village houses in Papua New Guinea. The number of anophelines infected with both parasites was greater than expected from the infection rates of each parasite and this difference was significant in resting collections. The excess of multiply infected mosquitoes is probably a result of a vector population composed of individuals with differing numbers of opportunities to become infected. Malaria-positive Anopheles punctulatus from resting catches had a significantly greater number of Stage 3 Wuchereria bancrofti larvae than malaria-negative mosquitoes. However, multiply infected mosquitoes appear to suffer greater mortality than non-infected or singly infected mosquitoes when the filarial worm reaches the third stage. Any potential increase in transmission resulting from multiple infections is thereby offset by a greater mortality rate in these mosquitoes. PMID- 2194154 TI - The use of biotin-labelled, synthetic DNA oligomers for the detection and identification of Plasmodium falciparum. AB - An oligonucleotide mixture based on the 21 base pair repeat sequence of Plasmodium falciparum was covalently coupled to biotin and used as a probe to detect P. falciparum DNA. The limit of detection was 10 ng. This method was further developed as a fingerprint assay for parasite strain typing. After restriction enzyme digestion, blotting and hybridization, distinct banding patterns were obtained for the strains tested and these were reproducible. In addition, discrete differences were found between PLF-3 S+/S-strains which may implicate genetic reorganization in the switching mechanism which occurs when parasites are passed from an intact to a splenectomized animal. PMID- 2194155 TI - Cerebrospinal fluid B2-microglobulin levels in meningeal involvement by malignancy. AB - Cerebrospinal fluid (CSF) and serum B2-microglobulin (B2m) levels were measured prospectively in 63 patients with hematological malignancies and 14 patients with solid tumours to evaluate the correlation between elevated levels and malignant infiltration of meninges. Serial CSF B2-m levels were also measured in 18 patients who received prophylactic intrathecal cytotoxic treatment. CSF B2-m levels were significantly higher in patients with central nervous system (CNS) involvement than in those without (p less than 0.001). A CSF B2-m level greater than 1.80 mg/L was closely associated with CNS disease (specificity 96%, sensitivity 76%) and CNS infiltration was also likely when the CSF B2-m level exceeded a simultaneously drawn serum level (specificity 98%, sensitivity 46%). Intrathecal methotrexate prophylaxis resulted in a consistent and significant rise in CSF B2-m levels with an average increase of 96% during a course of intrathecal injections. These results suggest that CSF B2-m levels may not be helpful for predicting early CNS relapse in these patients. However the CSF B2-m level and the corresponding serum B2-m level is a useful adjunct to the cytological diagnosis of CNS involvement by malignancy at presentation. Its value in predicting early CNS relapse and documenting response to CNS treatment requires further clarification. PMID- 2194156 TI - The role of mesangial cells in glomerular pathology. AB - The glomerular mesangial cell has become increasingly recognized as a multifunctional cell capable of mediating glomerular disease. This article reviews recent findings regarding the biology of these cells, and the relevance that these findings may have for our understanding of glomerular pathology. PMID- 2194157 TI - Comparison of flow cytometry and retrospectively applied static cytometry on lymphoid tissue. AB - Twenty cases of non-Hodgkin's malignant lymphoma were examined using both flow cytometry (FCM) and static cytometry (SCM) DNA analysis to detect aneuploidic cell populations. FCM was performed on fresh cell suspensions whilst SCM was performed retrospectively on formalin-fixed, paraffin-embedded samples of the same tissue. A total of 34 aneuploidic cell lines were detected by FCM compared to a total of 41 detected by SCM. Of the 20 cases 14 showed DNA indexes within 10% of each other for each method, indicating a reasonable degree of comparability between the two methods. Of the 6 cases which did not show comparable DNA indexes, 2 displayed similar cell lines for both methods, but the major abnormal cell populations were of different ploidy by SCM as compared to FCM. A qualitative comparison is thus possible between these two cases. The results suggest that retrospectively applied SCM ploidy analysis of lymphoid tissue is comparable to FCM on fresh tissue samples and can thus be used in retrospective studies of both prognostic and diagnostic significance. PMID- 2194158 TI - [Neoplastic associations of Brenner tumor. Apropos of a case associated with adenocarcinoma of the sigmoid]. AB - Neoplastic associations of Brenner tumor. About a case associated with the adenocarcinoma of the sigma. An unusual association of a Brenner tumor and an adenocarcinoma of the sigma is reported. A thorough review of the literature on the associations of Brenner tumor with other neoplasms is presented. In most cases Brenner tumor was associated with other ovarian tumors sharing, therefore, a common origin from the caelomic epithelium and all oestrogen dependent. Only rarely have associations with other tumors akin to the present been reported. PMID- 2194159 TI - Efficient site directed in vitro mutagenesis using ampicillin selection. AB - A novel plasmid vector pSELECT-1 is described which can be used for highly efficient site-directed in vitro mutagenesis. The mutagenesis method is based on the use of single-stranded DNA and two primers, one mutagenic primer and a second correction primer which corrects a defect in the ampicillin resistance gene on the vector and reverts the vector to ampicillin resistance. Using T4 DNA polymerase and T4 DNA ligase the two primers are physically linked on the template. The non-mutant DNA strand is selected against by growth in the presence of ampicillin. In tests of the vector, highly efficient (60-90%) mutagenesis was obtained. PMID- 2194160 TI - A temperature-sensitive mutant of Escherichia coli affected in the alpha subunit of RNA polymerase. AB - A temperature-sensitive mutant of Escherichia coli affected in the alpha subunit of RNA polymerase has been investigated. Gene mapping and complementation experiments placed the mutation to temperature-sensitivity within the alpha operon at 72 min. on the bacterial chromosome. The rate of RNA synthesis in vivo and the accumulation of ribosomal RNA were significantly reduced in the mutant at 44 degrees C. The thermostability at 44 degrees C of the purified holoenzyme from mutant cells was about 20% of that of the normal enzyme. Assays with T7 DNA as a template showed that the fraction of active enzyme competent for transcription was reduced as a function of assay temperature but that initiation and elongation were not significantly affected by the alpha mutation. A major effect on the fidelity of transcription was observed with the mutant enzyme, with misincorporation on two different templates stimulated about 4 fold at 37 degrees C. The role of the alpha dimer in the structure and function of RNA polymerase is discussed. PMID- 2194161 TI - Interaction of RNase P from Escherichia coli with pseudoknotted structures in viral RNAs. AB - In a previous study it was shown that RNase P from E. coli cleaves the tRNA-like structure of turnip yellow mosaic virus (TYMV) RNA in vitro (Guerrier-Takada et al. (1988) Cell, 53, 267-272). Cleavage takes place at the 3' side of the loop that crosses the deep groove of the pseudoknot structure present in the aminoacyl acceptor domain. In the present study fragments of TYMV RNA with mutations in the pseudoknot, generated by transcription in vitro, were tested for susceptibility to cleavage by RNase P. Changes in the specificity with respect to the site of cleavage and decreases in the rate of cleavage were observed with most of these substrates. The behaviour of various mutants in the reaction catalyzed by RNase P is in agreement with the present model of the TYMV RNA pseudoknot (Dumas et al. (1987), J. Biomol. Struct. Dyn. 263, 652-657). Base substitutions in the loop that crosses the shallow groove of the pseudoknot structure resulted, however, in an unexpected decrease in the rate of cleavage, probably due to conformational changes in the substrates. Studies on other tRNA-like structures revealed an important role in the reaction with RNase P for both the nucleotide at the 3' side of the loop that spans the deep groove and the nucleotide at position 4, which correspond to positions--1 and 73, respectively, in tRNA precursors. PMID- 2194162 TI - Poly(dA).poly(dT) rich sequences are not sufficient to exclude nucleosome formation in a constitutive yeast promoter. AB - It was suggested that poly(dA).poly(dT) rich sequences in yeast Saccharomyces cerevisiae act as elements of constitutive promoters by exclusion of nucleosomes (Struhl, K. (1985). Proc. Natl. Acad. Sci. USA 82, 8419-8423). We have mapped the chromatin structure of the pet56-his3-ded1 region in minichromosomes and show that the poly(dA).poly(dT) sequences are located in nuclease sensitive regions. DNA fragments from the nuclease sensitive promoter region of DED1 were used for nucleosome reconstitution in vitro. We show that all sequences can form nucleosome cores and that the poly(dA).poly(dT) sequence can be incorporated in nucleosome cores. The results suggest that the nuclease sensitivity found in vivo is not established by poly(dA).poly(dT) mediated exclusion of nucleosomes. PMID- 2194163 TI - Cloning, in vitro transcription, and biological activity of Escherichia coli 23S ribosomal RNA. AB - The 23S rRNA gene was excised from the rrnB operon of pKK3535 and ligated into pUC19 behind the strong class III T7 promoter so that the correct 5' end of mature 23S RNA was produced upon transcription by T7 RNA polymerase. At the 3' end, generation of a restriction site for linearization required the addition of 2 adenosine residues to the mature 23S sequence. In vitro runoff transcripts were indistinguishable from natural 23S RNA in size on denaturing gels and in 5' terminal sequence. The length and sequence of the 3' terminal T1 fragment was also as expected from the DNA sequence, except that an additional C, A, or U residue was added to 21%, 18%, or 5% of the molecules, respectively. Typical transcription reactions yielded 500-700 moles RNA per mole template. This transcript was used as a substrate for methyl transfer from S-adenosyl methionine catalyzed by Escherichia coli cell extracts. The majority (50-65%) of activity observed in a crude (S30) extract appeared in the post-ribosomal supernatant (S100). Activities catalyzing formation of m5C, m5U, m2G, and m6A residues in the synthetic transcript were observed. PMID- 2194164 TI - Transcriptional slippage occurs during elongation at runs of adenine or thymine in Escherichia coli. AB - A run of 11 adenine or thymine residues at the 5' end of an out-of-frame lacZ gene causes a high level of beta-galactosidase expression in E. coli. This effect was not observed for a run of guanine residues. Reverse transcription of mRNA isolated from E. coli containing the run of 11 A's reveals heterogeneity of transcript length while reverse transcription of mRNA isolated from S. cerevisiae containing the same gene shows no heterogeneity. Protein sequencing of the beta galactosidase molecules derived from the out-of-frame construct containing a run of adenines reveals the addition of a lysine at the run. A new method was developed where messages small enough to allow resolution of single nucleotide differences on an acrylamide gel are electrophoresed, electroblotted onto nylon and probed. This confirmed the reverse transcription results and showed that additional residues can be added to transcripts derived from DNA containing 10 or 11 thymine residues. A mechanism for slippage is discussed where the A-U rich RNA DNA hybrid can denature during elongation and rehybridize in an offset position, causing the addition of extra residues to the transcript. PMID- 2194165 TI - Advanced mammalian gene transfer: high titre retroviral vectors with multiple drug selection markers and a complementary helper-free packaging cell line. AB - We report the development of an advanced system for transfer and expression of exogenous genes in mammalian cells based on Moloney murine leukemia virus (Mo MuLV). Extensive deletion/mutagenesis analysis to identify cis-acting signals involved in virus transmission has led to the design of a family of novel, highly efficient retroviral vectors and a partner helper-free packaging cell line. The pBabe retroviral vector constructs transmit inserted genes at high titres and express them from the Mo MuLV Long Terminal Repeat (LTR). Each of these vectors has been constructed with one of four different dominantly acting selectable markers, allowing the growth of infected mammalian cells in the presence of G418, hygromycin B, bleomycin/phleomycin or puromycin, respectively. The high titre ecotropic helper free packaging cell line, omega E, was designed in conjunction with the pBabe vectors to reduce the risk of generation of wild type Mo MuLV via homologous recombination events. The omega E cell line was generated with separate gagpol and ecotropic env expression constructs with minimal sequence overlap and decreased sequence homology achieved by 'codon wobbling'. Homologous env coding sequences were deleted from the pBabe vectors without diminishing recombinant vector titre. Together, the pBabe vectors and omega E cell line should prove useful in experiments where highest frequencies of gene transfer, or concomitant expression of several different genes within a single cell are required with minimal risk of helper virus contamination. PMID- 2194167 TI - Nucleotide and amino acid polymorphism in the gene for L-histidinol dehydrogenase of Escherichia coli K12. PMID- 2194166 TI - E. coli promoter spacer regions contain nonrandom sequences which correlate to spacer length. AB - The -10 and -35 regions of E. coli promoter sequences are separated by a spacer region which has a consensus length of 17 base-pairs. This region is thought to contribute to promoter function by correctly positioning the two conserved regions. We have performed a statistical evaluation of 224 spacer sequences and found that spacers which deviate from the 17 base-pair consensus length have nonrandom sequences in their upstream ends. Spacer regions which are shorter than 17 base-pairs in length have a significantly higher than expected frequency of purine-purine and pyrimidine-pyrimidine homo-dinucleotides at the six upstream positions. Spacer regions which are longer than 17 base-pairs in length have a significantly higher than expected frequency of purine-pyrimidine and pyrimidine purine hetero-dinucleotides at these positions. This suggests that the nature of the purine-pyrimidine sequence at the upstream end of spacer regions affect promoter function in a manner which is related to the spacer length. We examine the spacer sequences as a function of spacer length and discuss some possible explanations for the observed relationship between sequence and length. PMID- 2194168 TI - Nucleotide sequence of the yeast SDH1 gene encoding a serine dehydratase homolog. PMID- 2194169 TI - Sequence analysis of the iclR gene encoding the repressor of the acetate operon in Salmonella typhimurium. PMID- 2194170 TI - Primer extension technique for the detection of single nucleotide in genomic DNA. PMID- 2194171 TI - Nurses left out of health care reimbursement reform. PMID- 2194172 TI - Definitions used in relation to gestational age. PMID- 2194173 TI - Fumes from the spleen. PMID- 2194174 TI - The case of Donnie J. PMID- 2194175 TI - Peptic ulcer disease in children. AB - Chronic gastroduodenal ulceration is the end product of an imbalance between acid levels, peptic hostile factors, and mucosal defenses. This condition differs significantly from stress ulceration, in which the primary factor is decreased mucosal blood flow, and from nonsteroidal anti-inflammatory drug-induced injury, in which there is local vascular injury and inhibition of prostaglandin synthesis. The identification of H pylori as a cause of chronic gastritis, duodenitis, and peptic ulcer is required for specific antibacterial therapy. PMID- 2194176 TI - Alopecia in children: the most common causes. AB - The differential diagnosis of alopecia in the pediatric age group is simplified by the fact that 90% to 95% of the cases are caused by four major entities: alopecia areata, telogen effluvium, tinea capitis, and trichotillomania. Careful examination of the scalp, hair, and historical pattern of the loss will usually be rewarded by the correct diagnosis. PMID- 2194177 TI - Retinopathy of prematurity. AB - Retinopathy of prematurity has reappeared in the neonatal nursery after largely disappearing 35 years ago. The major factor in its reemergence is the progressive improvement in neonatal care, resulting in salvage of infants who formerly would have been lost. Oxygen is now recognized to be but one of many interacting factors in the development of retinopathy of prematurity, with extreme immaturity being the primary factor. Methods of examination, classification and treatment of retinopathy of prematurity are discussed. PMID- 2194178 TI - Advances in vision and eye screening: screening at six months of age. AB - Eye and vision screening is a prototype preventative health measure. Increased knowledge of eye diseases in children and their treatment mandates much earlier screening than was recommended in the past. Advances in testing permit both the adoption of simpler and faster routine techniques and the application of more sophisticated and accurate screening methods. A thorough vision/eye screening at 6 months of age has been added to the previous examination schedule which only required screening at birth and again at 3.5-4 years of age. The simple scrutiny of the red fundus reflexes in the pupil with a direct ophthalmoscope (Bruckner test) provides superior screening for vision, binocular alignment and pathology in infants. The difficult-to-master cover test and its variants can be abandoned for screening purposes. In screening preverbal children, simple optotype charts (HOTV) are proving more efficient than the traditional 'tumbling E' game. Color vision testing should be added to the preschool examination. Vision screening in infants can be enhanced where resources permit by using new preferential looking tests and by employing sophisticated electrophysiological testing. Photographic screening methods based on the red reflex hold considerable promise for more efficient screening of children. PMID- 2194179 TI - Common ocular problems in children: conjunctivitis and tear duct obstructions. AB - Conjunctivitis, both in the newborn period and later, and nasolacrimal duct obstructions are common ocular problems facing all pediatricians. Conjunctivitis in childhood is separated into ophthalmia neonatorum and conjunctivitis at a later time. Gonococcus and chlamydia are the organisms causing the most concern in the neonatal period. Later, the diversity of causes becomes greater, but the consequences are smaller except for herpes simplex keratoconjunctivitis. Nasolacrimal duct obstructions are common in the first few months of life with most patients clearing spontaneously. Management is aimed at controlling symptoms until spontaneous resolution occurs or until the lacrimal system is probed. PMID- 2194180 TI - Diagnosis and management of childhood strabismus. AB - Strabismus is one of the most common ocular disorders encountered in children. The misalignment may be manifest in any field of gaze, may be constant or intermittent, and may occur at near or distant fixation or both. Early detection of strabismus is essential for restoration of proper alignment of the visual axes and the establishment of binocular vision. The proper assessment and management of a child with strabismus requires knowledge of the various clinical types, methods of detection and principles of treatment. PMID- 2194182 TI - Ocular emergencies in childhood. AB - Many ocular emergencies seen in children can be managed easily by the pediatrician. However, it is necessary to be comfortable with the definitions, etiologies of disease, important points in history taking, physical examination and laboratory evaluation and to know when referral is necessary. This paper outlines a number of the more common ocular emergencies seen in children. PMID- 2194181 TI - Ophthalmic neoplasms in infancy and childhood. AB - The most common ocular and orbital tumors presenting in infancy, childhood and adolescence are presented and discussed in this review. It has been prepared specifically for the clinical pediatrician and focuses on the clinical recognition of ophthalmic neoplasms, their diagnostic evaluation employing the use of advanced imaging techniques, biopsy when indicated and extent of disease workup. In addition, current treatment modalities are discussed. Ocular tumors addressed include: retinoblastoma, capillary hemangioma, lymphangioma, dermoid and epidermoid cysts, teratoma, glioma, astrocytic hamartoma, neurofibroma, rhabdomyosarcoma and fibrous tumors. Two aggressive and potentially fatal tumors, rhabdomyosarcoma and retinoblastoma, are presented in detail. In addition, the ocular tumors associated with the phakomatoses (von Hippel-Lindau, tuberous sclerosis and neurofibromatosis) are reviewed. PMID- 2194183 TI - Syndromes and systemic diseases with eye findings. AB - Many systemic and congenital diseases include ocular manifestations. Some are primarily ocular in importance, while others have a multiple-organ spectrum. The specific entities are the more frequently encountered diseases in a hospital or pediatric office practice. PMID- 2194184 TI - Learning disabilities and vision problems: are they related? AB - Vision problems can interfere with the process of learning. However, vision problems are not the cause of learning disabilities. If a child or adolescent is diagnosed as having a learning disability, refraction and eye muscle function must be assessed. If no disorders are found or, if found and corrected, the treatment of choice for the learning disability is special education. PMID- 2194185 TI - Habilitation and rehabilitation of visually impaired and blind children. AB - Important neurological, developmental and cognitive differences exist between the visually impaired and the sighted. Unless parents, health professionals, educators and other caregivers understand the differences, serious problems may arise. Certain aspects of development in visually impaired children have consequences for habilitation and rehabilitation. PMID- 2194186 TI - The Chianciano Conference to redefine chronic liver disease. PMID- 2194188 TI - Enema or Picolax as preparation for flexible sigmoidoscopy? AB - Two preparations for outpatient flexible sigmoidoscopy, Picolax and Klyx enemas, have been compared in a randomized controlled trial. There was no difference in efficacy between the two preparations, but patients preferred Picolax. PMID- 2194189 TI - Festschrift for Sir David Innes Williams. PMID- 2194191 TI - The Imperial Cancer Research Fund in the 1980s. PMID- 2194190 TI - Sir David Innes Williams--his contribution to postgraduate medical education and the training of overseas doctors. PMID- 2194192 TI - The impact of fetal diagnosis on the management of obstructive uropathy. PMID- 2194187 TI - Clinical pharmacology and therapeutics. PMID- 2194193 TI - Ureterocoeles. PMID- 2194194 TI - The General Medical Council: past, present and future. PMID- 2194195 TI - Evolving themes in the continent reconstruction of the lower urinary tract. PMID- 2194196 TI - Advances in hypospadias repair. PMID- 2194198 TI - Single- vs multiple-dose pharmacokinetics of clozapine in psychiatric patients. AB - Clozapine plasma levels were monitored in 16 patients during a series of three consecutive treatments (single dose-multiple dose-single dose). Each patient received a single 75-mg dose (3 x 25 mg) with clozapine tablets, and serial plasma samples were collected over 48 hr after the dose. At 48 hr, a multiple dose regimen was started, consisting of an initial dose escalation period followed by dosing at a constant regimen for at least 6 days. After the last dose, serial plasma samples were again obtained over 72 hr. Drug was then withheld for at least 7 days, a final single 75-mg dose was given, and plasma sampling was repeated. A subset of the patient population (N = 7) was used to test for a food effect during the single-dose treatments. The pharmacokinetic parameters between the initial and the final single dose periods were not significantly different. Similarly, there were no differences within patients when given the dose after fasting (fed 1 hr after dose) or with a meal. In contrast, the terminal elimination rate differed between the single-dose and the multiple-dose treatments (t1/2 m3 = 7.9 hr single dose and 14.2 hr multiple dose) (P less than 0.05) and the dose-normalized area under the plasma concentration/time curves increased 27% with multiple dosing. Since a previous study in patients (Choc et al., Pharm. Res. 4:402-405, 1987) showed dose proportionality of clozapine plasma concentrations during multiple-dose regimens, the present results cannot be described by Michaelis-Menten kinetics. PMID- 2194197 TI - Sustained-release delivery systems for treatment of dental diseases. AB - Sustained-release delivery systems allow the effective targeting of drugs for treating dental and periodontal diseases. Since dental diseases are chronic, the therapeutic agents used should persist in the oral cavity for as long as possible. Implanting fluoride, chlorhexidine, and other antiseptic agents embedded into sustained-release polymeric matrices into the oral cavity prevents cariogenic plaque accumulation. Both fibers and slab-like sustained-delivery devices bearing chemotherapeutic agents reduced periopathogenic bacteria levels associated with clinical improvement. This review provides useful background information for researchers seeking to develop controlled-release delivery systems for dental applications. PMID- 2194200 TI - Development of a sensitive activity assay for high-volume evaluation of human renin inhibitory peptides in rat serum: results with U-71,038. AB - A sensitive activity assay for high volume evaluation of human renin inhibitory peptides (RIPs) in rat sera (range 2-80 ng/ml) was developed based on the low affinity of RIPs to rat renin and their high affinity to human renin. The utility of this activity assay was tested by measuring concentrations of a human RIP, U 71,038 (BOC-Pro-Phe-N-MeHis-Leu psi [CHOHCH2]Val-Ile-Amp), in rat sera, determined by the activity assay, by a sensitive radioimmunoassay (RIA), and by tracking tritiated drug. Rats were given radiolabeled drug as an intravenous bolus, and blood samples were collected at various times after dosing. The serum level of U-71,038 equivalents was determined by the three techniques. Whole blood was also counted for total radioactivity to evaluate the potential for U-71,038 incorporation into red blood cells. Results from the three serum assays indicate good agreement between the calculated U-71,038 equivalents for the 30 min and 1 hr collection times. The 2 and 4 hr collection times show excellent agreement for the activity assay and RIA; [3H]-U-71,038 determinations gave substantially higher values. Serum levels for U-71,038 determined 30 min after dosing averaged less than 300 ng equivalents/ml suggesting that less than 1% of the administered dose was in the systemic circulation at that time. Thus, U-71,038 was rapidly cleared. At the 4 hr collection time, the level of U-71,038 equivalents, as determined by activity assay and RIA, was ten times the in vitro IC50 for the renin inhibitory activity of U-71,038.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2194199 TI - Bile salt-fatty acid mixed micelles as nasal absorption promoters of peptides. II. In vivo nasal absorption of insulin in rats and effects of mixed micelles on the morphological integrity of the nasal mucosa. AB - The effectiveness of mixed micelles in promoting nasal absorption of peptides has been demonstrated in vivo by employing insulin as a model compound. Insulin in the absence of adjuvants was not absorbed following intranasal administration. The results confirmed previous findings by others that absorption of insulin via alternative routes required absorption enhancers. Mixed micelles between NaGC and linoleic acid were found to rapidly deliver insulin into systemic circulation, with a concomitant decrease in plasma glucose. The extent of the hypoglycemic response was significantly greater than that produced by NaGC alone (55 vs 47%, P less than 0.05). Emulsion of linoleic acid, on the other hand, did not produce any significant insulin absorption. The findings thus supported previous in situ data that mixed micelles were more effective than NaGC or linoleic acid in promoting nasal absorption of peptides. Histopathologic examination of the rat nasal mucosa revealed that the extent of morphological alterations caused by mixed micelles was of mild to moderate severity even after 5 hr of exposure. However, studies involving more frequent and prolonged exposures are necessary to assess the practicality of these adjuvants before any clinical application can be attempted. PMID- 2194202 TI - [The action of insulin on the antioxidative enzymes and lipid peroxidation in the erythrocytes]. AB - The hormonal regulation of lipid peroxidation (LPO) and the status of the body antioxidant system has been studied insufficiently. The purpose of the present study was to investigate the effect of insulin on the activity of antioxidant enzymes (superoxide dismutase--SOD and catalase--CT) and at the same time on the level of LPO products in erythrocytes. Cells were incubated with insulin at different concentrations in own plasma for 2 h at 37 degrees C. It was shown that the incubation of erythrocytes with insulin in physiological concentrations (16.5 80 microU/ml) led to CT increased activity and made no effect on the content of conjugated dienes and dieneketones. A high concentration of the hormone (1000 microU/ml) caused an increase in the content of LPO products and did not influence CT activity. Changes in SOD activity were undetectable with regard to the experimental conditions. Thus, insulin regulating action on CT activity and LPO processes depends on insulin concentration. PMID- 2194201 TI - [The insulin receptor function of mononuclear leukocytes in pregnant women with diabetes mellitus]. AB - Investigation of the insulin-binding activity of insulin receptors (IR) in insulin treated pregnant women with insulin dependent diabetes mellitus with different requirement in insulin has shown that insulin-dependent diabetes in pregnant women in characterized by heterogeneity. Insulin therapy gets to normal the activity of insulin receptors in patients with diabetes mellitus with an increased affinity to IR, and causes no increase in the level of IR in patients in whom it was not raised. Insulin-binding activity in the latter may be associated with metabolic derangement caused by insulin insufficiency. PMID- 2194204 TI - [Hypoinsulinemia, hyperglycemia and circulating antibodies to the islet cells during the development of streptozotocin diabetes in rats]. AB - The time course of metabolic parameters and islet cell surface antibodies (ICSA) in low-dose streptozotocin (STZ)-induced diabetes in rats was studied, a total STZ dose being 160 mg/kg body weight. Two-phase diabetes development was observed. Initial mild hypoinsulinemia and hyperglycemia turned to more severe diabetes after day 24 which was preceded by the first ICSA peak at day 13. The second ICSA peak occurred at day 35. The data obtained suggest that in this model of diabetes the toxic STZ effect induces both the diabetic syndrome and humoral autoimmunity to beta-cells, and the latter leads to further impairment of diabetes. PMID- 2194203 TI - [The efficacy of using single-component insulin preparations in diabetes mellitus and generalized lipodystrophy]. PMID- 2194205 TI - [Hypoinsulinemia and lipid peroxidation in emotional-pain stress]. AB - The development of emotional pain stress in rats is accompanied by an increase in lipid peroxidation (LPO) products in the pancreas and a decrease in antiradical activity of its lipids. Hypoinsulinemia, of which a degree of expression is inversely proportional to an increase in peroxidation products, is observed. Antioxidant administration prevents LPO process activation in the pancreas and inhibits, to a great extent, a decrease in the level of insulin in stress. It is assumed that a certain role in the development of hypoinsulinemia in stress can be played by LPO processes resulting in the formation of active forms of oxygen and damage of the islands of Langerhans of B-cells. PMID- 2194206 TI - [Scano- and echography in the diagnosis of thyroid diseases]. AB - Echography was found more preferable in the differentiation of diffuse and nodular types of goiter and in the detection of thyroid cancer. Scanography was shown to be a valuable method for the determination of a shape, topography and function of the thyroid and its zones as well as in the diagnosis of autoimmune thyroiditis. PMID- 2194207 TI - [The breakdown of insulin by the enzymes of animal and human cells]. PMID- 2194208 TI - Computer-assisted analysis of chromosomal locations and transcriptional directions of Escherichia coli genes. AB - We present a computer-assisted method for locating and orienting nucleotide sequence segments on a large restriction map by comparing restriction fragment lengths. This method is based on the observation that long restriction fragments are rare and, therefore, the longest restriction fragments serve as effective discriminators. The method was applied to Escherichia coli genes, and chromosomal locations and transcriptional directions for more than 500 genes were determined. PMID- 2194209 TI - Escherichia coli K12 genomic database. AB - We have compiled the genomic nucleic acid sequence data of Escherichia coli K12 available from the existing major data collections and from the literature. The collected data are structured as a database for easy access and analysis. The sequence segments in the database are ordered by genetic map position. Sequence redundancy has been completely removed by combining overlapping sequences; therefore, our sequence data are amenable to statistical analysis. We have specified with a plus or minus (+ or -) on which of the two DNA strands the segment exists. The database currently contains a total of 954,392 bp, which corresponds to about 20% of the entire genome size. The sequence data are available on request. PMID- 2194210 TI - Psammoma bodies in metastatic carcinoma to the thyroid. AB - In a review of the 427 cases of thyroid with malignant neoplasm that were surgically resected at the Cancer Institute Hospital during the 10-yr period from 1978 to 1987, five cases of metastatic carcinoma to the thyroid were found. Psammoma bodies were histologically observed in three of the five cases. Primary thyroid carcinoma was highly suspected in the three cases, because psammoma bodies were detected during preoperative examinations that included image diagnosis and aspiration biopsy cytology. Thus, the presence of psammoma bodies in any kind of thyroid tumor should be carefully evaluated, both clinically and histologically, to ensure that the possibility of metastatic origin is not overlooked. PMID- 2194211 TI - Renal oncocytoma with cylindromatous changes: pathologic features and histogenetic significance. AB - We describe two cases of renal oncocytoma which showed an unusual light microscopic appearance characterized by nests of cells containing collections of eosinophilic hyaline material around and within oncocytic epithelial cell nests. Electron microscopy of the hyaline material showed a partly amorphous and partly lamellated structure, and immunohistochemistry for type IV collagen was positive. These cylindromatous changes are similar to the "glashelle Zylinder" of Billroth (Billroth T: Beobachtungen uber geschwulste der speicheldrusen. Virchous Arch [Pathol Anat] 17:357, 1859) described in adenoid cystic carcinoma and are most likely the result of an accumulation of basement membrane material in invaginations projecting into the surface of the basal plasmalemma. Since such invaginations occur in the normal distal tubule, our cases support origin of renal oncocytoma from distal tubular epithelial cells. PMID- 2194212 TI - Value of BCA-225 in the cytologic diagnosis of malignant effusions: an immunocytochemical study of 197 cases. AB - An immunocytochemical study of routinely prepared paraffin embedded cell block material from 72 effusions containing adenocarcinoma and 125 benign effusions was performed using a commercially available monoclonal antibody to the breast carcinoma associated glycoprotein BCA-225. Positive staining was observed in cells in 77.8% of the malignant effusions but not in any of the benign effusions. We conclude that BCA-225 is a highly specific and very useful discriminator in the differential diagnosis of adenocarcinoma and reactive mesothelial cells. However, because this marker is not expressed in all adenocarcinomas, studies with a panel of antibodies will provide better sensitivity. PMID- 2194213 TI - T-cell antigen-positive multiple myeloma. AB - We report the simultaneous expression of T-cell antigens on the myeloma cells from six patients with multiple myeloma (MM). These six patients come from a total population of 215 samples (115 direct samples, clinical incidence of 5.2%) of plasmacytic malignancies immunotyped at the University of Arizona. Four patients expressed T helper antigen (Leu 3, CD4), one expressed T-cell antigen receptor (Leu 4, CD3), and one expressed E-rosette antigen receptor (Leu 5, CD2). The presenting clinical features, histology, and plasma cell morphology showed no differences from multiple myeloma patients who did not express T-cell antigen. However, although the survival duration ranged from 5 to 93 mo overall, survival from demonstration of T antigen expression was very short, (2 to 7+ mo), with five of six (80%) patients dying less than or equal to 5 mo after study. The reason for T antigen expression is unknown. It may indicate that myeloma can arise from a normally minor subpopulation of B cells involved with immunoregulation; conversely, it could be a coincidental aberrancy associated with malignant change in the plasma cells. PMID- 2194214 TI - Follicular lymphomas in pediatric patients. AB - The clinicopathologic features of twenty cases of follicular lymphoma (FL) in pediatric patients are described. Fifteen boys and five girls were 2 to 20 yr (mean 10 yr) of age at diagnosis. In ten cases (50%) the lymphoma was localized in lymph nodes and in ten cases (50%) in extranodal sites. Fifteen patients had stage I, two stage II and three stage III disease at the time of presentation. The faucial tonsils were the primary site in seven cases, other head and neck sites in five, inguinal lymph nodes in four and possibly another, and the abdomen in two. Six cases (30%) were classified as follicular small cleaved cell type (FSCC), five (25%) as follicular mixed small cleaved and large cell (FMC), and nine (45%) as follicular large cell (FLC). The architectural pattern was purely follicular (F) in five cases (20%), predominantly follicular (F greater than D) in six (30%), follicular and diffuse (F = D) in six (30%) and predominantly diffuse (F less than D) in three (15%). In one case a progression from F greater than D LC to F less than D LC was documented. All patients attained complete remission (CR). One died of acute lymphoblastic leukemia 7 yr after the original diagnosis of FSCC non-Hodgkin's lymphoma (NHL), but the others are all alive and free of disease with a follow-up ranging from 6 mo to 16 yr (median 4 yr). In three patients therapy was initially deferred with no known adverse influence on outcome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2194215 TI - In situ hybridization using a biotinylated DNA probe on formalin-fixed liver biopsies with hepatitis B virus infections: in situ hybridization superior to immunochemistry. AB - In situ hybridization (ISH) using a biotinylated hepatitis B virus (HBV) DNA probe was compared with immunohistochemistry (IHC) using antibody to HBsAg in liver biopsies of 98 patients with HBV-related hepatitis. The positive reaction for ISH and/or IHC was demonstrated in 83 cases from 98 cases studied. In 60 cases, the findings of ISH and IHC were concordant, and in 20 cases, ISH showed evidence of HBV infection by detecting HBV DNA, but IHC did not. The study here confirms the advantages of ISH detecting HBV-DNA over IHC detecting HBsAg. Since ISH using biotinylated probe is simple and rapid, it may be used as a routine diagnostic procedure. PMID- 2194216 TI - Tumor-infiltrating T-lymphocytes in B-cell diffuse large cell lymphoma related to disease course. AB - Recent data from studies of experimental murine tumors and certain human tumors (primarily melanoma) suggest that tumor-infiltrating T-lymphocytes (T-cell TILs) represent a highly potent and specific host antitumor response. We conducted an immunohistochemical analysis of the T-cell TIL subpopulations in frozen tissue sections taken from 82 consecutive B-cell diffuse large cell lymphoma (DLCL) patients. Initially, we analyzed the relationship in these patients between relapse-free survival (RFS) and their T-cell TIL characteristics. Nineteen patients had a low percentage (less than 6% of Leu-2+ (suppressor/cytotoxic) T cell TILs, and 63 patients had a high percentage (greater than 6%) of Leu-2+ TILs. We found that a low percentage of Leu-2+ TILs correlated with a reduction in RFS: at 20 mo follow-up, all 19 low Leu-2+ patients had relapsed, whereas 70% of the 63 high Leu-2+ patients remained relapse-free (P = 0.008). No significant correlations appeared between patients' T-cell TIL subsets and overall survival. The percentage of newly diagnosed tumors with low counts of Leu-4+ (pan-T) TILs was marginally greater among interleukin-2 (IL-2) receptor-positive tumors than among IL-2 receptor-negative tumors (50 versus 28%, P = 0.098), which suggests that specific phenotypic characteristics of B-cell DLCL may modulate the host T cell TIL response. Our results indicate that the host's T-cell TIL response in B cell DLCL can be quantitated from frozen tissue sections and that this response may be related to disease course. Further related TIL studies may lead to new immunorestorative therapeutic approaches for patients with deficient or aberrant cytotoxic T-lymphocyte host responses. PMID- 2194217 TI - Correspondence re: S.J. Maygarden and E. L. Flanders. Mycobacteria can be seen as "negative images" in cytology smears from patients with acquired immunodeficiency syndrome. Mod Pathol 2:239, 1989. PMID- 2194218 TI - Protein secondary structure and circular dichroism: a practical guide. PMID- 2194219 TI - The characterization of recombinant mouse glandular kallikreins from E. coli. AB - A system has been developed for the expression in E. coli of 12 of the 14 expressed mouse submandibular gland kallikreins as cassettes subcloned directly from cDNA. Using the epidermal growth factor binding protein (mGK-9) and the gamma-subunit of nerve growth factor (mGK-3), as test cases, mature processed forms, obtained as functionally active proteins, as well as various precursor forms, were isolated. The expression system described allows rapid isolation of kallikrein protein from corresponding cDNA with yields of approximately 1.0 mg of purified protein from 10 g of initial cell paste. This expression system will facilitate structure/function studies of the mouse glandular kallikrein gene family and help elucidate the regions of the mature proteins responsible for the diverse catalytic behavior and growth factor interactions observed in this family of proteins. PMID- 2194220 TI - Auditory adaptations for prey capture in echolocating bats. PMID- 2194221 TI - Mammalian muscle spindle: peripheral mechanisms. AB - The responses of sensory endings of the muscle spindle to stretch are produced by transduction in the sensory terminals and by impulse initiation in the sensory axon, both of which appear to be largely linear and non-time-dependent processes. The marked nonlinearity of spindle responses to length, the processes of gain compression, and the aftereffects of fusimotor activity and of stretch appear to reside mainly in the mechanical properties of the intrafusal fibers. Although the basis of the dynamic sensitivity of the primary ending in the passive spindle is still not well understood, dynamic fusimotor effects have been shown to depend on activation of the bag 1 fiber. Static fusimotor actions result from contraction in the bag 2 and/or chain fibers. Certainly, a great deal is known about the muscle spindle at the level of changes in sensory discharge to variations in muscle length and to fusimotor stimulation, although new insights continue to arise from experiments of this type. However, there is a need for further quantitative information that will lead to greater understanding of transduction mechanisms, impulse initiation, and intrafusal fiber contractile activation. PMID- 2194222 TI - Nitrogen metabolism and ornithine cycle function. PMID- 2194223 TI - Cardiovascular purinoceptors. PMID- 2194224 TI - Light response of vertebrate photoreceptors. PMID- 2194225 TI - Renal medullary microcirculation. PMID- 2194226 TI - Genetic analysis of transfer and incompatibility functions within the IncHI plasmid R27. AB - This study was undertaken to establish a transfer complementation system for IncH plasmids and to locate regions of incompatibility within the HI1 plasmid, R27. Two regions of R27 were found to contribute to incompatibility as determined by incompatibility testing with fragments of R27 cloned in cosmid vectors. One of these regions hybridized with the IncHI1 rep probe (Couturier et al., Microbiol. Rev. 52, 375-395, 1988). Complementation analysis was carried out using transfer deficient mutants of R27 in combination with pHH1508a. Cosmid vectors, which contained cloned restriction fragments of R27, were able to complement selected R27 Tra- mutants, enabling the transfer-deficient plasmid to transfer at near normal frequencies. Complementation of R27 Tra- plasmids by pHH1508a at both 26 and 37 degrees C was shown to occur, but was host-dependent in its degree. These results suggest that the transfer mechanisms of IncHI and IncHII plasmids are related. PMID- 2194227 TI - Characteristics of the nopaline catabolic plasmid in Agrobacterium strains K84 and K1026 used for biological control of crown gall disease. AB - Wild-type Agrobacterium radiobacter strain 84 and its Tra- derivative K1026, used for biological control of crown gall disease, each contain the plasmid pAtK84b. It confers incompatibility to tumor-inducing (Ti) plasmids of pathogenic A. tumefaciens, thus preventing transfer of Ti plasmids into K84 and K1026, and the consequent development of pathogens resistant to the specific antibiotic, agrocin 84 produced by K84 and K1026. pAtK84b also resembles one group of Ti plasmids in its capacity for directing nopaline catabolism. A study of the DNA homology among pAtK84b, pTiC58, and pTiAch5 was carried out. pAtK84b was transferred by conjugation to a plasmidless recipient and, after isolation, was hybridized with Ti plasmid DNA. Areas of DNA homology were located on published maps of pTiC58 and pTiAch5, a restriction enzyme map of pAtK84b was constructed, and areas of homology with DNA of known genetic function were located on the map. Strong and extensive (over 50%) homology was found between pAtK84b and pTiC58 (nopaline catabolic, Noc), but much less between pAtK84b and pTiAch5 (octopine catabolic). There was no detectable homology between pAtK84b and the oncogenic T-DNA and virulence (Vir) regions of either Ti plasmid. The size of pAtK84b was 173 kb and the orientation of regions of identified gene function (Noc, incompatability/origin of replication, and conjugal transfer) on pTiC58 was matched by the locations of homologous areas on pAtK84b. It is concluded that pAtK84b may be a deletion product of a pTiC58-type plasmid which has been disarmed in the oncogenic T-DNA and Vir regions. PMID- 2194228 TI - Variation of oxygen requirement with plasmid size in recombinant Escherichia coli. AB - We have previously found an inverse relationship between certain cell growth parameters and plasmid size for a series of recombinant Escherichia coli strains containing pUC8 or one of a series of pUC8 recombinant derivatives. To extend these results we investigated whether there was a similar variation among our strains in oxygen requirement, which might be related to the differences in growth. During logarithmic growth in shake flasks, oxygen uptake by E. coli strain JM103 containing an 8.7-kb pUC8 derivative (pBS5) was 2.5 times that of JM103 harboring pUC8 (2.7 kb) and 7.5 times that of plasmid-free JM103. Supplementing the medium with acetate eliminated both the growth disadvantage of and the increased oxygen uptake by the strain harboring pBS5 compared with that containing pUC8. In all cases oxygen consumption decreased drastically as cells began and then continued into stationary phase, and no significant difference was seen among the three strains at these times. When the three strains were grown in a fermentor with continuous monitoring of oxygen levels, plasmid-free JM103 outgrew JM103 containing pUC8 or pBS5 at three levels of aeration. The latter two strains grew identically when aeration was high; their growth curves diverged, however, when aeration was low. In the fermentor experiments the point at which the growth of the three strains diverged was coincident with the point of oxygen depletion in the cultures. PMID- 2194229 TI - Diversity of the Chlamydia trachomatis common plasmid in biovars with different pathogenicity. AB - The 7.5-kb plasmid of Chlamydia trachomatis (CT) is believed to encode essential genes and might have a role in CT pathogenicity. Accordingly, analysis of plasmid linked mutations in isolates from biovars with different pathogenic properties should help in identifying which plasmid-encoded genes, if any, may be involved in modulating virulence. For this purpose, the plasmid present in a low-virulence isolate (trachoma biovar, serotype D) was cloned and sequenced. Nucleotide changes were experimentally checked against the sequence of the plasmid variant from the highly virulent strain L2/434/Bu (LGV biovar). By aligning our data with two published sequences of different trachoma and LGV variants a general consensus structure was determined, comprising eight major open reading frames (ORF) and a number of points where there is consensus only between isolates of the same biovar (biovar-specific mutations). The degree of variation between different isolates is less than 1%. In particular, comparison of serotype-D and L2 plasmids shows mutations which are generally silent or lead to few (one to four), often conservative, amino acid changes in ORFs 1, 2, 4, 5, 6, and 7. The protein encoded by ORF8 is completely conserved. In contrast, the polypeptide variants encoded by ORF3 show nine amino acid changes, seven of which are due to biovar-specific mutations. PMID- 2194230 TI - Cloning of Bacteroides fragilis plasmid genes affecting metronidazole resistance and ultraviolet survival in Escherichia coli. AB - Since reduced metronidazole causes DNA damage, resistance to metronidazole was used as a selection method for the cloning of Bacteroides fragilis genes affecting DNA repair mechanisms in Escherichia coli. Genes from B. fragilis Bf-2 were cloned on a recombinant plasmid pMT100 which made E. coli AB1157 and uvrA, B, and C mutant strains more resistant to metronidazole, but more sensitive to far uv irradiation under aerobic conditions. The loci affecting metronidazole resistance and uv sensitivity were linked and located on a 5-kb DNA fragment which originated from the small 6-kb cryptic plasmid pBFC1 present in B. fragilis Bf-2 cells. PMID- 2194231 TI - A yeast-Escherichia coli shuttle vector containing the M13 origin of replication. AB - A yeast-Escherichia coli shuttle vector containing the M13 origin of replication has been constructed. This vector allows selection and replication in both Saccharomyces cerevisiae and E. coli, as well as single-stranded packaging from E. coli upon infection with a helper phage. The presence of a polylinker with various unique restriction sites facilitates the cloning of desired genes. PMID- 2194233 TI - The European Behavioural Pharmacology Society. PMID- 2194232 TI - Molecular characterization of the vir regulon of Agrobacterium tumefaciens: complete nucleotide sequence and gene organization of the 28.63-kbp regulon cloned as a single unit. AB - The entire vir regulon of Agrobacterium tumefaciens was subcloned and the complete 28.6-kbp nucleotide sequence was determined. The regulon was cloned as a single unit into two replicons, one of which replicates at a high copy number in this bacterium, and a second which has broad-host-range features to replicate in other Gram-negative bacteria. These vir region plasmids are able to confer in trans the processing and transfer activities on a second plasmid containing the T DNA. In the high copy number vir region plasmid pUCD2614, a moderate increase in basal vir gene expression was observed as judged by virE::cat fusion expression assays relative to the wild-type control plasmid. Furthermore, higher efficiencies of tobacco leaf disk transformation were observed than with the widely used vir helper plasmid pAL4404. The nucleotide sequence studies showed that the vir region consists of 28,631 bp comprising 24 open reading frames which encode proteins involved in tumorigenicity. Two open reading frames not previously characterized, virH and ORF5, were uncovered within the virD/virE intervening spacer region. Together these studies more completely characterize the structure and function of the vir regulon. PMID- 2194234 TI - Current status of small-bowel ultrasound. AB - Ultrasonography offers direct imaging of the bowel wall and allows dynamic evaluation of peristalsis. It helps to differentiate eosinophilic gastroenteritis from regional enteritis and lymphoma, displays a typical appearance in intussusception and is quite specific in the afferent loop syndrome, closed-loop obstruction and lymphedema. It may be helpful in ischemia of the bowel and in the evaluation of acute appendicitis. PMID- 2194235 TI - [Roentgen studies of the small bowel]. AB - Diseases of the small bowel are rare and this part of the gastrointestinal tract is the most difficult to explore radiologically. The examination results correlate directly with the indications. Whatever examination technique is used, it should be based on fluoroscopy. For most radiologists the combined single and double-contrast examination with air or methylcellulose is probably the most suitable. The interpretation should be done in a logical, stepwise way and with access to clinical information. PMID- 2194236 TI - [General motility disorders of the small bowel]. AB - Gastroenterologists are displaying increasing interest in small-bowel motility disorders. This paper reports on the investigation of motility disorders of the small bowel with a standardized enteroclysis technique with barium and methylcellulose. The method can detect both disturbed motility and morphological changes. Examples of different causes (neurogenic-humoral factors, malabsorption, intestinal wall disease, ischemia and vascular disorders) are described. In some patients the finding of disturbed motility is the only observation of any clinical significance. In others it may be helpful in establishment of correct diagnosis or narrowing of the differential diagnosis. The efficiency and accuracy of small-bowel radiology can be improved by this method. PMID- 2194237 TI - [Computerized tomography of the small bowel]. AB - Computer tomography (CT) is an imaging technique that reveals most useful information in the presence of extramucosal diseases of the small bowel. It is indispensable as a guide to treatment. After a short description of the examination technique and the normal anatomy, the authors describe the CT manifestations of small-bowel diseases, especially inflammatory and neoplastic lesions. PMID- 2194239 TI - [Evolutionary origin of the intracellular oligogenic system]. PMID- 2194238 TI - [Status of scintigraphy in small bowel diseases]. AB - Radionuclide studies have an established place in the evaluation of small bowel disease; in particular they allow the demonstration of active bowel bleeding with the aid of labeled erythrocytes and the diagnosis of an inflammatory bowel process or formation of an abscess with the aid of labeled leukocytes. PMID- 2194240 TI - [Beta structure of polypeptide]. PMID- 2194241 TI - [The beta structure--proteins and synthetic polypeptides]. PMID- 2194242 TI - [Characteristics of lung volume and expiratory flow seen in black Africans adults]. AB - We have measured lung volumes, ventilatory flows, and the main thoracic dimensions in 65 Togolese adults aged between 25 and 55. We found that for Africans the total lung volume was 25% less and other lung volumes were 22% less than those for Caucasians. The difference in the total lung capacity was explained by smaller thoracic dimensions in Africans than in Caucasians of the same height; for the same TLC the residual volume was lower and the expiratory flows were higher in Africans than in Caucasians. The difference was most prominent on the proximal instantaneous flows giving a forced expiratory flow volume curve which was less straight and more concave at the end of expiration. Greater muscular strength, a larger diameter of the airways, and different alveolar development in the Africans may explain the differences. PMID- 2194243 TI - [Thoracic computed tomography data and cytology of the bronchoalveolar lavage fluid in an adult case of Niemann-Pick disease. The physiognomy of the disease in Tunisia]. AB - From a personal observation of a case of the chronic type-B form Niemann-Pick's disease in a 23 year old adult, the authors decided to review all the Tunisian published cases. They bring to light, in a review of the literature, the pulmonary disorder that occurs during this disease and discuss the contribution of computed tomography and the value of broncho-alveolar lavage as a method of diagnosis and prognosis in this disorder. PMID- 2194244 TI - Polar cap formation during cell division in Escherichia coli. PMID- 2194245 TI - Cytoskeletal elements and calcium: do they play a role in the Escherichia coli cell cycle? PMID- 2194246 TI - The Escherichia coli cell cycle. PMID- 2194247 TI - Involvement of cell shape in the replication and segregation of chromosomes in Escherichia coli. AB - Chromosome replication appears to initiate in E. coli when the dnaA boxes in oriC become filled with DnaA protein, which could simultaneously mediate both the unwinding of the origin for the start of polymerization and the attachment of oriC to the cell envelope (Bramhill and Kornberg, 1988; Lobner-Olesen et al., 1989; Pierucci et al., 1989). The attachment takes place somewhere within the cell half in which the oriC resides. The boundaries of this attachment/replication zone, which cannot include the polar cap, could be demarcated by the polar and centrally located periseptal annuli (Rothfield, this Forum). Since attachment and polymerization are two aspects of the same process, the attachment probably takes place via the polymerizing strand. Once polymerization begins, the oriC with the older template strand moves away from the younger one, by mechanisms unknown, to eventually take up residence in the equivalent domain of the complementary sister cell. Thus, the template strand that stays within its domain corresponds to the strand that was attached during the previous round of replication, and the template that moves away is the one that was not attached. The driving force for this translocation is not specified by our model, but a number of plausible alternatives have been proposed by others (reviewed in Leonard and Helmstetter, 1990). Throughout the ensuing replication and cell division, the chromosomes are located (or can move freely) within the attachment/replication zone of the developing daughter cell (lateral cylinder and septum). At some time during the course of this process, but before the next initiation event, the replication origins must be released from the attachment sites so that the entire process can be repeated. Thus, the probabilistic non random chromosome segregation is due to the asymmetry of the attachment/replication zone in the cell, whereas the partitioning system itself must possess a mechanism to discriminate between template strands of different ages. This apparent mechanistic relationship between chromosome replication, chromosome partitioning and the maintenance of cell shape may provide an interesting framework for future experiments. PMID- 2194248 TI - Role of the nucleoid in the toporegulation of division. PMID- 2194249 TI - Partitioning of nucleoids. PMID- 2194250 TI - Localization of septation sites. PMID- 2194252 TI - 4th Forum in Microbiology. Cell shape and division in Escherichia coli. PMID- 2194251 TI - Genes and the replication cycle of Escherichia coli. PMID- 2194254 TI - Aspects of cell cycle regulation. PMID- 2194253 TI - Structure and metabolism of the murein sacculus. PMID- 2194255 TI - [The role of immunoglobulins in pulmonary diseases]. PMID- 2194256 TI - [Myocardial metabolism and perfusion assessed by positron emission tomography]. PMID- 2194257 TI - Benign lesions of the gastrointestinal tract that may be misdiagnosed as malignant tumors. AB - Benign lesions of the gastrointestinal tract (GIT) that may be misdiagnosed as malignant tumors are described and illustrated in this review. The clinicopathologic features that are important for the accurate diagnosis of each lesion are presented in detail. The entities chosen for discussion include inflammatory pseudotumors (IPT), pseudosarcomatous granulation tissue in GI polyps, pseudocarcinomatous invasion in GI polyps, and GI ulcers induced by radiation and chemotherapy. PMID- 2194258 TI - Pathologic assessment of liver cell dysplasia and benign liver tumors: differentiation from malignant tumors. AB - Recent developments in the pathologic assessment of several benign hepatic processes are reviewed, with particular emphasis on distinguishing these processes from malignant lesions. Liver cell dysplasia remains a controversial lesion, with mounting evidence to support its preneoplastic nature. Adenomatous hyperplastic nodules are large regenerative nodules in cirrhotic livers, and may also have malignant potential. Distinguishing these nodules from hepatocellular carcinoma by histology may become increasingly important, with the advent of more sensitive imaging techniques. Differentiating features of noncancerous biliary epithelium versus well-differentiated cholangiocarcinoma, sclerosing hemangioma versus epithelioid hemangioendothelioma, and angiomyelolipoma versus the clear cell variant of hepatocellular carcinoma are also presented and discussed. PMID- 2194259 TI - Benign pulmonary lesions that may be misdiagnosed as malignant. AB - Five benign pulmonary lesions that may be misdiagnosed as malignant tumors are reviewed. In three lesions, diagnostic problems arise when a spindle cell component is dominant and obscures other characteristic histologic features. In the inflammatory pseudotumor, correct diagnosis relies on recognition of the benign cytology of the spindle cells and identifying a typical admixture of plasma cell-rich inflammatory cells. For spindle cell carcinoids, useful diagnostic features are the organoid pattern, benign cytology, and neuroendocrine differentiation features of the spindle cells. Localized pleural mesothelioma (fibroma) is composed of benign spindle cells in a fibrocollagenous background; mesothelial differentiation is not present by ultrastructural or immunocytochemical analysis. In sclerosing hemangioma, a complex histology may suggest a number of malignancies. Observation of solid and papillary areas of benign tumor cells, as well as sclerosis of vessel walls and intervening areas, will allow correct diagnosis. Pseudolymphoma, a nodular benign lymphoid infiltrate, is distinguished by its polymorphous and polyclonal composition and numerous germinal centers. PMID- 2194260 TI - Benign cutaneous lesions potentially misdiagnosed as malignant neoplasms. AB - Presented are five benign skin lesions that have features simulating malignant skin lesions. Although not a comprehensive review of all such potentially troublesome lesions, those reviewed here include (1) keratoacanthoma, (2) desmoplastic trichoepithelioma, (3) sclerosing hemangioma, (4) phototoxic drug eruption, and (5) pigmented spindle cell nevus. Those features, allowing their separation from malignant lesions, are presented. PMID- 2194262 TI - Benign breast lesions that mimic malignant tumors: analysis of five distinct lesions. AB - Interpretation of breast biopsies has assumed a large and important component of the surgical pathologist's practice. Currently, about 10% of women will develop breast carcinoma during their lifetime. This high incidence, coupled with increased public awareness of breast disease, greater use of screening mammography to detect early carcinomas, development of multiple therapeutic options (the latter often influenced by the pathology of the tumor), and a harsh medicolegal climate have placed greater demands on surgical pathologists for accurate interpretation of breast tissues. The focus of this report is to define the clinicopathologic features of five benign breast lesions that mimic malignant breast disease, and thus pose important diagnostic considerations to surgical pathologists. PMID- 2194261 TI - Diagnostic dilemmas in gynecologic and obstetric pathology. AB - Four difficult differential diagnoses in gynecologic and obstetric pathology are reviewed. These include (1) sarcoma-like mural nodule in ovarian tumors versus ovarian sarcomas, (2) early blastocyst versus choriocarcinoma, (3) hydropic abortus versus partial hydatidiform mole, and (4) regressing implantation site versus placental site trophoblastic tumor. The author's own interpretation and recommendations are presented. PMID- 2194263 TI - Application of the theory of finite mixtures for the estimation of 'cure' rates of treated cancer patients. AB - I assume the survival function of treated cancer patients to be a mixture of two subpopulations, with c equal to the proportion who will die of other causes, and 1--c the proportion who will die of their disease. Using census data, I estimate the parameters of the survival distribution of those patients dying of other causes, and then use follow-up data to determine the maximum likelihood estimates of the proportion constant c and the parameters of the survival function of those dying of their disease. I illustrate the methodology using data from a prospective clinical trial in breast cancer. PMID- 2194264 TI - Application of new two-sample tests to data from a randomized placebo-controlled heart-failure trial. AB - In a randomized placebo-controlled double-blind trial of 230 congestive heart failure patients, four treatments were evaluated for efficacy, with exercise tolerance time (ETT) as the primary outcome. Various two-sample tests were applied to the analysis of ETT data. It is shown in this paper that the conventional two-sample tests (t and rank-sum) are insensitive to situations where the effect of the experimental therapy is not consistent across a patient population. Tests recommended by O'Brien are more appropriate for these data. It is also shown that the application of the O'Brien tests led to the identification of sub-groups where the observed effect of the experimental therapy was most pronounced. PMID- 2194265 TI - Immunotherapy and immunoprophylaxis in the newborn infant: the need for definitive clinical trials. PMID- 2194267 TI - Complement deficiency and neutrophil dysfunction as risk factors for bacterial infection in newborns and the role of granulocyte transfusion in therapy. AB - The similarity in the susceptibility to bacterial infections of newborns and older patients with complement deficiencies, neutropenia, or neutrophil function defects has suggested that neutrophils and/or complement might also be defective in newborns. Although no individual element of the phagocytic host defense system is severely deficient, several partial deficiencies have been identified. These involve important amplification pathways of complement and neutrophil activation and may combine to cause significant decreases in phagocyte activity at sites of infection. Because of decreased specific antibody, initial activation of the classical complement pathway is decreased. Low levels of C3 and factor B decrease amplification by the alternative pathway and result in marked decreases in opsonization and generation of chemotactic activity from C5. There are also quantitative and qualitative neutrophil defects. The recent observations that newborns' neutrophils are relatively deficient in membrane expression of their major adherence protein/C3bi receptor help explain the decreased mobility and phagocytic activity of these cells. Thus, several partial deficiencies combine to cause severe impairments in delivery of neutrophils to sites of infection and contribute to the increased susceptibility of the newborn to infection. PMID- 2194266 TI - Neonatal susceptibility and immunity to major bacterial pathogens. AB - Neonatal bacterial sepsis has continued in this decade to contribute significantly to neonatal mortality and morbidity and is a critical determinant of outcome in infants of very low birth weight despite the availability of antibiotics. The group B Streptococcus and Escherichia coli are the predominant pathogens for the newborn infant. Studies on the epidemiology, microbiology, and immunology of group B streptococcal disease are more extensive than those on E. coli disease. Type-specific antibodies, polymorphonuclear leukocytes, and complement are integral to immunity against group B Streptococcus, and experimental data are presented to support the importance of these components. The newborn infant is handicapped by temporary deficiencies in host defenses, and approaches for restoring immunocompetence, such as immunization of the mother or passive administration of intravenous immunoglobulins or other immune factors, are presented for consideration. Further studies are required to demonstrate the safety, feasibility, and efficacy of these approaches. PMID- 2194268 TI - Epidemiology and potential methods for prevention of neonatal intestinal viral infections. AB - Viral infections of the gastrointestinal tract remain a major problem during the neonatal period. In addition to causing acute diarrhea, rotaviruses and other enteric viruses may be involved in the pathogenesis of necrotizing enterocolitis and other neonatal enteric diseases. There are several potential methods for the prevention and treatment of gastrointestinal viral infections. Antiviral immunoglobulins might be used to inhibit intestinal viral replication. Since only small concentrations of serum immunoglobulins are present at mucosal surfaces, oral administration of immunoglobulins might be utilized to maximize antiviral efficacy. Alternatively, inhibitors of specific glycoproteins of virus-cell binding might be used to prevent the productive infection of intestinal epithelial cells. In addition, since many enteric viruses require proteolytic enzymes for protein cleavage, protease inhibitors may prove effective for inhibition of intestinal viral replication. At this time, these methods have proven useful for the inhibition of rotavirus infection in experimental animals. The successful application of these and other methods for the prevention of enteric infections in humans might substantially reduce the morbidity and mortality associated with enteric diseases in high-risk neonates. PMID- 2194269 TI - Role of fibronectin in diseases of newborn infants and children. AB - Fibronectin is a large-molecular-weight glycoprotein present on most cell surfaces, in extracellular fluids, and in plasma. Both cell-associated and soluble fibronectin are thought to have important roles in the inflammatory response and host defense and may contribute to the maintenance of microvascular integrity during septic episodes. Newborn infants have levels of fibronectin in plasma that are one-third to one-half those found in the healthy adult. In addition, neonates with respiratory distress syndrome, perinatal asphyxia, bacterial sepsis, intrauterine growth retardation, or postnatal malnutrition have a further depression in their plasma levels of fibronectin. The low plasma concentration of fibronectin in newborn infants may contribute to the hypofunction of the neonatal reticuloendothelial system and predispose to the development of sepsis. Rates of synthesis of plasma fibronectin are diminished in the neonate, and an inverse correlation between fibronectin half-life and gestational age exists. The role of fibronectin in treatment or prophylaxis of neonatal sepsis remains to be determined. PMID- 2194270 TI - Intravenous gammaglobulin in the prophylaxis of late sepsis in very-low-birth weight infants: preliminary results of a randomized, double-blind, placebo controlled trial. AB - The efficacy of intravenous immunoglobulin (IVIG) as prophylaxis for late sepsis was evaluated in a placebo-controlled, randomized, double-blind trial involving 240 infants of very low birth weight (less than 1,300 g). Each infant received a total of five doses of either IVIG (1 g/d) or an albumin placebo. The first four doses were administered between days 1 and 5 of life, and the last dose was administered on day 15 or shortly thereafter. Preliminary analysis of data available for 126 patients showed that in the first 30 days, sepsis developed in nine of 61 patients given IVIG and in 16 of 65 given placebo (one-tailed P = .065). At 70 days, the number who developed sepsis was similar in the two groups: 20 for those who received IVIG vs. 23 for those who received placebo. When patients with coagulase-negative staphylococcal infections were deleted from the totals, the results were essentially the same, i.e., three of 61 who received IVIG vs. nine of 65 who received placebo (one-tailed P = .041), developed sepsis during the first 30 days and 12 of 61 vs. 13 of 65, respectively, had developed sepsis at 70 days. In the IVIG group, the median peak level of serum IgG at day 7 was 1,700 mg/dL and the IgG levels were significantly greater than those in the placebo group for days 7-42. These data suggest that infusions of IVIG at the doses and dosing intervals used in this study may be effective in decreasing the incidence of late-onset sepsis during the first month of life in infants of very low birth weight. PMID- 2194271 TI - Immunoprophylaxis of infections with respiratory syncytial virus: observations and hypothesis. AB - Infections with respiratory syncytial virus (RSV) may cause substantial morbidity and increased mortality in neonates and infants, especially those born before term and/or with pulmonary or cardiac disease. Humoral immunity was long thought to play only a small role in prevention, reduction of severity, or recovery from RSV infections of the lower respiratory tract. We recently performed a series of experiments in RSV-infected cotton rats, owl monkeys, and human infants to assess the role of humoral immunity in the prevention or recovery from RSV infections. This report summarizes studies utilizing intravenous IgG (IVIG) administered parenterally or topically (into the lower airway) for prophylaxis or treatment of RSV infections of the lower respiratory tract. The prophylactic administration (parenteral or topical) of IVIG to cotton rats or its therapeutic administration to RSV-infected cotton rats, owl monkeys, or humans significantly reduced RSV replication. The reductions in titers of virus correlated positively with titers of RSV-neutralizing antibody. Clinical trials are indicated to determine whether parenteral IVIG prophylaxis might prevent serious RSV infections in high-risk infants. PMID- 2194272 TI - Potential use of intravenous immune globulin for group B streptococcal infection. AB - Several lines of evidence suggest that passive immunization as adjunctive therapy for or prevention of group B streptococcal (GBS) sepsis in neonates will require the use of preparations of human intravenous immune globulin (IVIG) that are hyperimmune for protective antibodies to GBS. Results from both in vitro and in vivo experiments utilizing commercially available IVIG preparations suggest that the doses necessary for achieving levels of pathogen-specific antibody capable of promoting efficient opsonization and phagocytosis of GBS may be prohibitive. Several laboratories have reported that standard IVIG preparations contain only modest levels of antibodies to the four capsular polysaccharides of GBS (the protective moieties), are variable in their effect on in vitro opsonophagocytosis by dose and method of preparation, and are significantly less protective in animal models than is IVIG prepared from adults immunized with GBS polysaccharide vaccines. Further, when we gave a single infusion of standard IVIG at a dose of either 500 or 750 mg/kg to 10 premature neonates during the first week of life, opsonophagocytosis of type III GBS by their sera and adult neutrophils was observed only when high levels of specific antibody were achieved, levels only transiently achieved in nonimmune infants. Commercial preparation of human immune globulin hyperimmune for GBS will be required for optimal adjunctive therapy in patients with sepsis due to GBS and for the possible prevention of late-onset infant disease. PMID- 2194273 TI - Polyvalent group B streptococcal immune globulin for intravenous administration: overview. AB - Immunoglobulin therapy is becoming an important modality for the prevention and treatment of bacterial and viral infection. Standard intravenous immunoglobulin (IVIG) is made from large pools of plasma obtained from normal blood donors. However, lot-to-lot variation in titers of antibody to specific microbial pathogens may diminish therapeutic efficacy. Since group B Streptococcus (GBS) is an important neonatal pathogen, a preparation with high titers of activity against GBS was prepared and studied. Plasma was obtained from volunteers immunized with a polyvalent GBS vaccine and was processed by the Swiss Red Cross for intravenous infusion. This high-titered GBS intravenous immunoglobulin (GBS IVIG) was shown to be superior both in vitro and in vivo to standard IVIG. GBS IVIG provided protection when therapy was delayed for up to 24 hours after infection. Standard IVIG did not protect animals against all GBS strains. However, GBS-IVIG enhanced survival from infection with all strains tested, even when the challenge dose of GBS was increased by 2 log units. Specific hyperimmune globulins to pathogens such as Haemophilus influenzae and Streptococcus pneumoniae have also been studied. Immunization of adult volunteers as a means of obtaining hyperimmune globulin appears to be an effective method of producing high-titered pathogen-specific preparations of IVIG. PMID- 2194274 TI - Unit length as the denominator for quantitation of cell proliferation in nasal epithelia. AB - Cell proliferation data, generally based on a labeling index (LI), provide a valuable endpoint for assessment of toxic and potentially carcinogenic responses in laboratory animals. Measurement of the LI is time consuming because of the large number of cells that need to be counted to determine the denominator. In respiratory mucosa, the total cell count of the surface epithelia may be altered in response to treatment, either through cell loss or increases in cell number (e.g., hyperplasia). As an alternative to the more conventional LI, the present studies were carried out to assess the value of expressing cell proliferation in nasal epithelia as a unit length labeling index (ULLI), defined as labeled cells per mm of basement membrane. Rats were exposed by inhalation to formaldehyde or methyl bromide, and changes in cell proliferation were determined in the respiratory and olfactory epithelia, respectively, using both total cell count and basement membrane length as denominators. Total cell counts were clearly influenced by treatment, while basement membrane length was not. Both methods revealed similar treatment-induced effects on cell proliferation, and in fact were highly correlated (R greater than or equal to 0.92, p less than 0.001). It was concluded that the ULLI method provides an effective alternative to total cell counts and the LI method. This approach is not influenced by alterations in the total cell population, and has the benefit of being less labor intensive than LI determinations. PMID- 2194276 TI - Picking computer programs that will work for you. PMID- 2194277 TI - Home care: charting that makes it through the Medicare maze. PMID- 2194275 TI - High resolution light microscopic morphological and microvascular changes in an acutely induced renal papillary necrosis. AB - Morphological changes were followed in semi-thin glycolmethacrylate sections, after treating male Wistar rats with a single ip dose of 2-bromoethanamine (BEA) hydrobromide (100 mg/kg) to induce renal papillary necrosis. Medullary interstitial cells had irregular nuclei at 4 hr and focal necrosis by 8 hr which spread from the papilla tip to the cortico-medullary junction from 12 hr. Increased mucopolysaccharide staining was observed in the papilla tip at 4 hr, and was lost from those regions where necrosis had developed by 48 hr. Endothelial platelet adhesion, first seen at 8 hr, was very marked at 18 hr, but affected capillaries in necrotic regions only, up to 144 hr. The absence of extravasated Monastral Blue B demonstrated the integrity of the medullary microvascular endothelia. The distal nephron showed degenerative changes at 12 hr and cell exfoliation at 18 hr. Cortical changes were confined to PAS-positive casts in the collecting duct and loop of Henle from 8 hr and dilatation of distal and proximal tubules at 8 and 72 hr, respectively. There was active repair at the junction between viable and necrotic tissue in the papilla from 24 hr with mitoses in the collecting ducts and loops of Henle. Normally the urothelium is less than 3-4 cells thick, but upper urothelial proliferation followed BEA administration. Hyperplasia was especially marked at the mouth of the ureter and in the pelvis opposite the region of necrosis (7-8 cells thick at 18 hr) and had only partially resolved by 144 hr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2194278 TI - [Early detection of prostatic cancer]. PMID- 2194279 TI - [Attempted liver graft: 25 years after]. PMID- 2194281 TI - [Resin-bonded bridges--current trends]. PMID- 2194280 TI - The renin angiotensin system in diabetes mellitus. A physiological and therapeutic study. AB - The purpose of this study was to measure components of the renin angiotensin system in patients with type 1 diabetes mellitus, with and without nephropathy, to study the renal sensitivity to angiotensin II in uncomplicated type 1 diabetes and to investigate the short and long-term renal effects of angiotensin II reduction with angiotensin converting enzyme inhibitors in patients with diabetic nephropathy. In patients with type 1 diabetes without complications, plasma renin activity, angiotensin II and aldosterone levels were normal. In patients with diabetic nephropathy, renin levels were elevated, probably partly as a result of diuretic treatment. However, renin levels were also elevated compared to patients with other renal diseases who had similar treatment and degree of azotemia. The renal sensitivity to angiotensin II was normal in patients with uncomplicated diabetes. The reduction in glomerular filtration rate and renal plasma flow and increases in filtration fraction during A II infusion were equal to those in healthy controls. Nine days' captopril treatment in 15 patients with diabetic nephropathy induced an increase in renal plasma flow and a decrease in filtration fraction. The glomerular filtration rate remained unchanged. During 8 weeks' randomised enalapril or metoprolol treatment in 40 patients with diabetic nephropathy, enalapril treatment reduced proteinuria to half the initial value. Metoprolol treatment had no effect on proteinuria. Furosemide was also used and the dosage was adjusted to give equally effective blood-pressure control in both groups. During long-term treatment with captopril in patients with diabetic nephropathy, the rate of decline in kidney function over time was reduced to one fourth the initial value even though the blood pressure was only slightly reduced. The renin angiotensin system appears to be functionally intact in diabetes mellitus and interruption by ACE inhibition reduces proteinuria both by blood pressure reduction and by an effect independent of systemic blood pressure. Long-term treatment might protect kidney function in diabetic nephropathy to a greater extent than would be expected from the blood-pressure-lowering effect alone. PMID- 2194282 TI - [Oral candidiasis: epidemiology, diagnosis and treatment]. AB - Oral candidiasis, an opportunistic infection increasingly often met, includes many clinical aspects where oral thrush is the best known. The etiology is often iatrogenic but candidiasis also represents the most frequent opportunistic infection in HIV infection. To avoid recurrences, therapy must begin with elimination of factors which have promoted its development. Imidazoles appear to furnish the most effective antifungal therapy. PMID- 2194283 TI - [The neuromuscular effect of anterior guidance on the protrusive movement pattern of the mandible. Observations in the horizontal plane]. AB - The influence of a temporarily altered anterior guidance on mandibular movement patterns of tooth-guided and non-guided protrusion was examined in a clinical study on 20 patients, all with complete sets of teeth. Registration and recordings of movements were done with the computer-aided ultrasonic measuring system MT 1602. Based on an average measuring time of 40 min for each patient the main results were as follows: 1. The shape of the anterior guidance strongly influences the horizontal tracings of tooth-guided and non-guided protrusion. In most cases these tracings show a deviation from the mid-sagittal path due to neuromuscular coordination. 2. Insertion of an idealized, symmetrical anterior guidance or a horizontal plateau lessens the mandibular deviation and harmonizes the tooth-guided and non-guided paths. However, the old neuromuscular engrams are not completely erased. 3. Newly formed engrams can be erased much easier than old ones. PMID- 2194284 TI - [The replica prosthesis. A simple method for prosthesis duplication]. PMID- 2194285 TI - [Case report: bonded prosthesis restoration]. PMID- 2194287 TI - [The importance and value of bonded prostheses]. PMID- 2194286 TI - [A randomized crossover study. N-acetylcysteine lozenges sweetened with xylitol do not induce the formation of dental plaque]. PMID- 2194288 TI - Light-evoked changes in the interphotoreceptor matrix. AB - The normal function of vertebrate photoreceptor cells depends on multiple interactions and transfer of substances between the photoreceptors and the retinal pigment epithelium (RPE), but the mechanisms of these interactions are poorly understood. Many are thought to be mediated by the interphotoreceptor matrix (IPM), a complex extracellular matrix that surrounds the photoreceptors and lies between them and the RPE. Histochemical, immunocytochemical, and lectin probes for several IPM constituents revealed that components of the IPM in the rat undergo a major shift in distribution or molecular conformation after the transition between light and dark. In the light, various IPM constituents concentrated in bands at the apical and basal regions of the outer segment zone; in the dark, they distributed much more uniformly throughout the zone. The change in IPM distribution was triggered by the light-dark transition; it was not a circadian event, and it was not driven by a systemic factor. The light-evoked change in IPM distribution may facilitate the transfer of substances between the photoreceptors and the RPE. PMID- 2194289 TI - Cloning of a transcriptionally active human TATA binding factor. AB - Transcription factor IID (TFIID) binds to the TATA box promoter element and regulates the expression of most eukaryotic genes transcribed by RNA polymerase II. Complementary DNA (cDNA) encoding a human TFIID protein has been cloned. The human TFIID polypeptide has 339 amino acids and a molecular size of 37,745 daltons. The carboxyl-terminal 181 amino acids of the human TFIID protein shares 80% identity with the TFIID protein from Saccharomyces cerevisiae. The amino terminus contains an unusual repeat of 38 consecutive glutamine residues and an X Thr-Pro repeat. Expression of DNA in reticulocyte lysates or in Escherichia coli yielded a protein that was competent for both DNA binding and transcription activation. PMID- 2194290 TI - A cDNA for a protein that interacts with the human immunodeficiency virus Tat transactivator. AB - The human immunodeficiency virus (HIV) tat protein (Tat) is a positive regulator of virus gene expression and replication. Biotinylated Tat was used as a probe to screen a lambda gt11 fusion protein library, and a complementary DNA encoding a protein that interacts with Tat was cloned. Expression of this protein, designated TBP-1 (for Tat binding protein-1), was observed in a variety of cell lines, with expression being highest in human cells. TBP-1 was localized predominantly in the nucleus, which is consistent with the nuclear localization of Tat. In cotransfection experiments, expression of TBP-1 was able to specifically suppress Tat-mediated transactivation. The strategy described may be useful for direct identification and cloning of genes encoding proteins that associate with other proteins to modulate their activity in a positive or negative fashion. PMID- 2194291 TI - Transrectal ultrasonography in prostatic carcinoma. AB - Transrectal ultrasonography of the prostate is a diagnostic technique allowing visualization of the internal anatomy of the prostate gland, the seminal vesicles, and the prostatic urethra. Although there is still considerable controversy about its reliability, indications for transrectal prostatic ultrasonography include the following: diagnosis of prostate cancer, guidance of transrectal needle biopsies, guidance of staging biopsies, staging previously diagnosed prostate cancers, monitoring treatment response, and assessing glandular size and volume. PMID- 2194292 TI - Quantitative fluorescence image analysis--a bladder cancer diagnosis alternative. PMID- 2194294 TI - Participation in breast screening programs: a review. AB - Despite recommendations by the American Cancer Society and other organizations for use of screening mammography, data on reported utilization of this procedure by American women show that these guidelines are not being met. We reviewed published studies that reported participation rates or that examined factors associated with participation in selected breast screening programs. In general, women at high risk due to age and family or personal history of breast disease were not more likely to participate in breast screening programs than women without those risk factors. The one group of variables that was fairly consistently associated with participation was the practice of other preventive health behaviors. Women who expressed more concern about their health and who were more knowledgeable about breast cancer screening and its benefits also were more likely to complete mammography. Approaches to increasing participation are discussed in the context of the literature on this subject. PMID- 2194293 TI - Anticipatory grief: a review. AB - In this review the term anticipatory grief is defined and described. Misconceptions about the reaction which may have been applied in previous literature are noted and their origin discussed. Empirical studies of the impact of an anticipatory grief reaction on subsequent adjustment are presented, with a discussion of the reasons for their disparate results and suggestions for future research. The relevance to the clinician of the anticipatory grief reaction in both family and professional caregivers is considered. PMID- 2194295 TI - The rational use of antischistosomal drugs in schistosomiasis control. AB - The paper examines the available antischistosomal drugs in Zimbabwe and the use of population-based chemotherapy as an effective strategy of morbidity reduction in schistosomiasis control. The problems of poor drug efficacy and side-effects that were associated with earlier antischistosomal drugs have largely been overcome with the advent of recent, safe and effective oral drugs. The main constraints of population-based chemotherapy are the costs of drug procurement, transport and the logistics of delivery. In highly endemic areas, screening for infection may not be necessary and following pilot surveys mass chemotherapy can be carried out. Nevertheless, anecdotal and unverified reports suggest that mass chemotherapy may result in lightly infected individuals losing their residual immunity and risk heavy reinfection. To lower costs of the drugs and reduce organizational problems of delivery it may be preferable to target treatment at high risk groups. These groups include certain age classes with peak prevalence and intensity of infection and those predisposed to get heavy infections. Treatment prevents the development of overt disease in these high risk groups and also significantly reduces contamination and consequently transmission. However, chemotherapy only results in temporary relief and its impact requires to be sustained by parallel and long-lasting interventions that include improved sanitation, better water supplies and health education. Suggestions are made on how to train and utilize community and public health workers for such control programmes. PMID- 2194296 TI - Immunohistochemical demonstration of subclasses of inflammatory cells and active, collagen-producing fibroblasts in the synovial plicae of lumbar facet joints. AB - Plical tissue removed perioperatively from lumbar facet joints was studied immunohistochemically with the avidin-biotin-peroxidase complex (ABC) method for a putative presence of various subclasses of inflammatory cells and active collagen-producing fibroblasts. These methods have previously been used successfully for demonstrating specific inflammatory cells in rheumatoid arthritic synovium and cervical ligament and for studying regeneration of connective tissue, respectively. An overt inflammatory cellular response could not be demonstrated, as B lymphocytes were totally absent and no lymphocyte activation markers, either interleukin-2 receptor or immune-response-associated Ia antigens were expressed. Most of the immunoreactive cells observed were CD11b monocytes, and even these were only scattered in the connective tissue. Occasional activated collagen-producing fibroblasts were seen, suggesting in these few cases a possible regenerative response of the collagenous tissue, maybe induced by an impingement phenomenon, as such cells are not normally seen in resting connective tissue. PMID- 2194297 TI - Cerebellopontine angle tumours in black South Africans--how rare are acoustic schwannomas? AB - Previous reports of intracranial neoplasms from Africa have all shown a very low incidence of acoustic schwannomas (neuromas). In this series a group of 11 cerebellopontine angle solid tumours from black Africans were studied. On conventional histological examination only 3 had the features of a schwannoma. However, by using immunohistochemistry, a further 3 examples were identified. As controls, the same antisera were also applied to known schwannomas and meningiomas. During the period of the study, 163 patients with primary intracranial neoplasms were seen and thus acoustic schwannomas accounted for 3.7%. Although this figure is low by world standards, it still represents a far higher figure than has previously been reported from Africa. This study therefore emphasises the value of immunohistochemistry in the diagnosis of brain tumours and, furthermore, shows that acoustic schwannoma must be considered in the appropriate clinical setting, even in a group previously regarded as low-risk. PMID- 2194298 TI - Isolated tricuspid valve infective endocarditis. A report of 6 cases. AB - Six cases of isolated tricuspid valve endocarditis in young women are described. Preceding genital sepsis was a predisposing factor in 4 patients. Cardiac signs are unusual at presentation, rendering the diagnosis difficult. Pleuropulmonary manifestations are the predominant findings, while overt signs of tricuspid insufficiency and right heart failure occur late in the disease. Staphylococcus aureus is the pathogen most commonly found and requires energetic treatment for a minimum of 4 weeks. The value of echocardiography in establishing an early diagnosis is stressed. Persistent sepsis constitutes a major indication for surgery. PMID- 2194299 TI - [Idiopathic myelofibrosis: clinical course, survival, and causes of death in a series of 60 patients]. AB - The evolutive patterns, actuarial survival and causes of death of idiopathic myelofibrosis were analysed in a series of 60 patients. The median age of the patients was 64 years; 41 were males and 19 females. In the initial bone-marrow biopsy studies 25 patients were in stage MF/C, 17 in MF/O- and 18 in MF/O+. When performing this analysis, 32 patients were dead, 19 were still alive and 9 had been lost after a median follow-up of 6 months. The median survival of the whole series was 57 months. Four major evolutive patterns were recorded: 1) blastic crisis (7 cases), 2) portal vein hypertension (4 cases), 3) liver insufficiency due to massive myeloid metaplasia of the liver without signs of portal vein hypertension (5 cases); in 2 of them this pattern followed splenectomy), and 4) heart failure ascribable, at least partially, to post-transfusion haemochromatosis (3 cases). The blastic crisis appearing in 7 patients presented after a median follow-up of 19 months, and 6 of these patients have died after a median of 5 months since the diagnosis of the blastic crisis. In the 16 patients who died without any characteristic evolutive pattern, the following causes of death could be registered: septic shock (6 cases), intracranial haemorrhage, haemoperitoneum and acute renal failure (1 case each), whereas the cause of the deceased was unclear in the remaining 7 patients. PMID- 2194300 TI - [Methods for the characterization of platelet membrane glycoproteins]. PMID- 2194301 TI - [The clonogenic cell in acute myeloblastic leukemia]. PMID- 2194302 TI - Oxygenation of human tumors. AB - The objective of this article is to summarize current knowledge of oxygen supply to human tumors and of tumor tissue oxygenation, parameters which go hand in hand, and in turn critically determine the cellular metabolic microenvironment of human malignancies. A compilation of available data on these factors is presented. Though data on human tumors in situ are scarce and there may be significant errors associated with the technique used for measurements, experimental evidence is provided for the existence of a compromised and anisotropic oxygen supply to many tumor cells. Comparable to experimental rodent tumors, O2-depleted areas develop in many human malignancies which coincide with nutrient and energy deprivation, and with a hostile metabolic microenvironment. Significant variations in these relevant parameters have to be expected between different locations within the same tumor, at the same location at different times, and between individual tumors of the same grading and staging. Therefore, evaluation of the oxygenation status in individual tumors before therapy might be most beneficial for designing specifically tailored treatment protocols for individual subjects in order to improve tumor response to treatment. PMID- 2194303 TI - Prognostic factors for patients with osseous metastasis: a multi-institutional prospective study. AB - A multi-institutional prospective study for the analysis of prognostic factors for patients with osseous metastasis was performed. From February 1986 through June 1988, a total of 216 patients were included in this study. Cox's regression model made it clear that the most significant overall prognostic factor was primary site (p = 0.0002). In the lung cancer group, performance status (p = 0.0036) and metastasis of organs than bone (p = 0.0105) were also significant prognostic factors. In the breast cancer group, no significant factors were obtained. In the hepatoma group, the values for alkaline phosphatase (ALP) (p = 0.0021), lactate dehydrogenase (LDH) (p = 0.0195), and sex (p = 0.0264) proved significant. In the group of other cases, the most significant prognostic factor was the value for urinary hydroxyproline/creatinine ratio (p = 0.0001), followed by the pain score of RTOG (p = 0.0018). These factors and actual survival periods obtained in this study will be useful for the future stratification of patients for individualized optimal radiation schedules. PMID- 2194304 TI - [Hyperfractionated irradiation with simultaneous cisplatin chemotherapy in patients with far-advanced carcinoma of the head and neck]. AB - From January 1988 to April 1989, 22 of 28 patients with advanced carcinomata of the head and neck have been treated by hyperfractionated radiotherapy (2 x 1.2 Gy/day, five days/week, total dose 74.4 to 79.2 Gy) and simultaneous application of Cisplatinum (20 mg/m2 day, i.v., five days in the first and fifth week of the radiotherapy). In 68% of the patients the treatment could be applied in full dose. All eight patients with primary application of a gastrostomy could be irradiated without split, whereas five of 14 patients without a gastrostomy had a split of greater than or equal to 2 weeks. The mucositis healed in all patients after the end of the irradiation. Up to now, no serious complications have been seen. One year cumulative locoregional control rate is 65%. This study serves as a pilot study for a randomized trial. According to the acute and subacute toxicity the applied treatment is feasible. PMID- 2194305 TI - Dynamics of postirradiation intracellular cysteine and aspartic proteinases profiles in proliferating and nonproliferating mammalian cells. AB - Dynamics of postirradiation intracellular cysteine and aspartic proteinases profiles were examined in proliferating and nonproliferating Chinese hamster fibroblasts (V79). The results show that there are significant alterations in cysteine and aspartic intracellular proteinases activity already in the early postirradiation period, which are different in proliferating and nonproliferating cells. Irradiation of the cells examined to low doses and up to 15 Gy induced an increase in cysteine proteinases activity in the early postexposure period, while at higher irradiation doses applied, the activity of these proteinases was decreased. These observations suggest that intracellular proteinases are actively participating in process involving recovery from radiation injury or cell killing. PMID- 2194306 TI - Intraocular pressure: new perspectives. AB - Reevaluation of normal intraocular pressure (IOP) was attempted to investigate possible background factors that contribute to variations in IOP. It is well known that IOP increases with age among Western populations, while in the Japanese IOP has been confirmed to decrease with aging. Such paradoxical results can not be reasonably explained without considering systemic conditions rather than local factors peculiar to different races. Accumulated evidence indicates that IOP is positively correlated with blood pressure, obesity and other cardiac risk variables. Incorporation of these factors by stratifying the sample may provide the baseline IOP in those who are different in systemic conditions. PMID- 2194307 TI - Refracting the corneal graft. AB - Patients who have undergone penetrating keratoplasty have unique postoperative refractive requirements. These include irregular astigmatism, high corneal toricity, and anisometropia. We present a stepwise clinical approach for accurate, efficient refraction of these patients, utilizing visual acuity measurement, retinoscopy, subjective refraction, keratometry, photokeratoscopy, and diagnostic rigid contact lens application. PMID- 2194308 TI - Molteno implant surgery in refractory glaucoma. AB - In recent years aqueous drainage implants have become a useful adjuvant in the treatment of refractory glaucomas. The Molteno implant is one of the most widely used devices for providing a permanent channel of aqueous flow from the anterior chamber to a collecting reservoir in the posterior subconjunctival space. Recently, modifications in design and surgical technique of the Molteno implant have enhanced its success rate, with a reduction in complications such as prolonged hypotony, anterior chamber flattening, and tube-corneal touch. These modifications include intracamerally injecting hyaluronic acid, using a needle track to provide an opening into the anterior chamber for the tube, performing the operation in two stages, using a double plate, temporarily ligating the tube, using a donor scleral patch, and giving adjunctive antifibrotic therapy. The rationale for application of the Molteno implant, the indications, techniques, results, and complications are described. PMID- 2194309 TI - Spasmus nutans--or is it? AB - At age 3 1/2 years a child developed what appeared to be classic spasmus nutans. Thorough discussions as to the propriety of neuroimaging studies in such patients are presented. With this late age of onset, the presence of a compressive lesion was suspected and neuroimaging demonstrated a sellar-suprasellar mass lesion. PMID- 2194310 TI - Prospects for epidermal growth factor in the management of corneal disorders. AB - Epidermal growth factor (EGF) is a naturally occurring mitogen which, in its recombinant form, is under intensive investigation for therapeutic use. Receptor activation by EGF induces up-regulation of synthesis of specific proteins as well as proliferation and differentiation of the corneal epithelium, keratocytes, and endothelium both in vivo and in vitro. With topical application of EGF, corneal wounds could possibly heal within hours, and the strength of the stromal scars is also increased; this may lead to the prospect of sutureless surgery. It may be possible to treat degenerative and dystrophic disorders of the cornea, especially of the endothelium, and to enhance the density of endothelial cells in donor corneas prior to transplantation. Combination therapy with EGF, fibroblast growth factor, and corticosteroids may be advantageous in producing a synergistic effect. It is possible that, with increased knowledge of the pharmacokinetics and the development of appropriate delivery systems, EGF could become an integral part of the next generation of ophthalmic pharmaceuticals. PMID- 2194311 TI - From a forester's boy to a university professor. AB - Austrian ophthalmologist, Dr. Karl B. Hruby, is well known for his present lens, which allows slit-lamp examination of the vitreous and fundus. He is also known as one of the first to use microsurgical methods for intraocular operations and scleral buckling for retinal detachments. In this memoir, Dr. Hruby shares the fascinating personal account of his experiences as a prisoner and physician during World War II, and as an outstanding teacher and clinician thereafter. The article is followed by the editorial comment of Dr. Fred Blodi, who invited Dr. Hruby to contribute this article. PMID- 2194312 TI - Obstructive sleep apnea syndrome. AB - The diagnosis and treatment of obstructive sleep apnea syndrome (OSAS) is a field of emerging interest to a wide variety of professionals, including dentists. OSAS is now widely recognized as a common clinical disorder with potentially life threatening consequences. The syndrome is characterized by repeated episodes of upper airway obstruction during sleep. The most prominent clinical manifestations are loud snoring during sleep and daytime hypersomnelence. Bypassing the area of obstruction with a tracheostomy results in an improvement in clinical symptoms. The dentist's role may be to fit a simple mechanical device for anterior repositioning of the mandible, which recently has been introduced as a less invasive mode of treatment, when the cause is functional rather than anatomical. PMID- 2194313 TI - Excitotoxins and amyotrophic lateral sclerosis. AB - Recent data suggest that amiotrophic lateral sclerosis (ALS) could be the result of motoneuron damage induced by endogenous or exogenous excitotoxins, and especially by excitatory amino acids (EAA). Three main sources support this hypothesis: 1) The induction of experimental models of motor neuron disease by 2 excitotoxins (BOAA and BMAA). 2) Evidence of disordered glutamate metabolism in ALS. 3) Data suggesting that EAAs may be a factor in the pathogenesis of other degenerative neurologic diseases (Huntington disease and Alzheimer disease). This new "excitotoxin hypothesis" of ALS is of particular interest as several effective antiglutamate agents are now available for human therapeutic trials. PMID- 2194314 TI - Effects of gemfibrozil on lipids and haemostasis after myocardial infarction. AB - The effects of gemfibrozil on haemostatic variables were studied in 43 survivors of myocardial infarction with serum triglycerides (TG) greater than or equal to 2 mmol/l 2 weeks prior to randomization. The study was double-blind, placebo controlled and stratified for chronic betablockade. Twenty-two individuals were given gemfibrozil 600 mg twice daily and 21 individuals received matching placebo. After 8 weeks the TG level was unchanged in the placebo group, whereas a 44% reduction was noted in the gemfibrozil group (p less than 0.001). Fibrinogen increased in both groups, while bleeding time and platelet count were unchanged. Clotting factor VII-phospholipid complex decreased in both groups, but the change was more marked and attained statistical significance only in the gemfibrozil group (60% reduction, p less than 0.01). By DDAVP-stimulated D-Dimer agglutination test 8 in 21 patients in the placebo group (38%) still had reduced fibronolytic capacity versus none in the gemfibrozil group (p = 0.001). Thus, in this study, gemfibrozil improved reduced fibrinolytic capacity and may have reduced hypercoagulability by lowering the clotting factor VII-phospholipid complex. PMID- 2194315 TI - Antithrombin III Kumamoto: identification of a point mutation and genotype analysis of the family. AB - We previously reported a variant antithrombin III (AT III Kumamoto) associated with a 31-year-old female who suffered from recurrent thrombotic episodes. To define the molecular basis for the variant AT III, we used a combination of genomic amplification followed by cloning, sequencing, and hybridization with allele-specific oligonucleotide probes. We obtained evidence for a cytosine to thymine transition in exon 2 (codon 47) of the AT III gene in the proband. This mutation converts arginine 47 to cysteine. Oligonucleotide hybridization procedures were used for confirmation of the mutation and for genotype analysis of the family members. PMID- 2194316 TI - Observations on the cell biology of tissue factor in endothelial cells. AB - Human umbilical vein endothelial cells (HUVEC) are inducible for tissue factor (TF) activity in culture. Based on experiments using ECGF (4-20 micrograms/ml) with heparin (90 micrograms/ml), we obtained the following results: 1) In confluent HUVEC cultures, ECGF had essentially no influence on the levels of inducible TF. 2) In growing HUVEC cultures, ECGF reduced the TF response shortly after seeding but full response was regained when cells were kept confluent for 2 3 days. 3) Although secondary cultures responded best to TF induction in the absence of ECGF, the response was essentially equal over at least 8 passages in the presence of ECGF. 4) Of total cellular TF induced in HUVEC, about 25% was available on the surface, and less than 4% was released with the shed plasma membrane vesicles. The proportion of total TF activity available on the surface of intact cells was not influenced by the presence of ECGF. 5) T1/2 for the decay of TF activity induced was 8.3-9.5 h, whereas in HUVEC when protein synthesis was blocked after TF induction a T1/2 of about 30 h was found. PMID- 2194317 TI - [Care systems for alcohol-related problems in 90 years. From psalm singing and compulsory work to ambulatory treatment and the Minnesota model]. AB - The article describes the development of the Norwegian systems for treatment and care of persons with alcohol-related problems during the last 90 years. The first institutions were run by religious organizations. Public interest was low, and the social framework consisted of compulsory regulations and a focus on clients with severe problems. Following World War II the disease concept of alcoholism was developed. This provided the system with new optimism, and more differentiated and medically oriented treatment. In 1970 the forced labour institutions were closed down, and new institutions were established which provided care. However, the inadequately staffed treatment centres, had a difficult time. Towards the end of the decade scientists started attacking the old myths about alcohol and "alcoholism". During the 1980s all programmes of treatment and care were regionalized, and the systems for treatment and care of persons with alcohol-related problems have become more closely linked to other health and social welfare services in society. Less severely handicapped clients are approached, and the focus is on out-patient treatment. It has become more usual to involve clients' families/social networks. A new system of private institutions is developing. These function in accordance with the Minnesota model, which again highlights the concept of alcoholism as a disease. PMID- 2194318 TI - [Change of insulin strength in Norway--a study of an information campaign]. AB - This article describes and discusses the effects of an information campaign carried out in 1987 when the strength of the insulin solution was changed from u 40 to u-100. The data comprised drug sales statistics, records of errors, questionnaires to pharmacies and hospitals and press cuttings. The campaign was organized by a group of experts appointed by the Directorate of Health. Local activities were carried out by pharmacies and hospitals, which proved to be effective information channels. Almost all diabetics changed to u-100 over a three-month period. We recorded incidents of serious erroneous prescribing and administration of insulin, but no deaths or irreversible injuries. It was more difficult to reach target groups of health personnel in the primary health care. The change led to a distinct and probably permanent rise in the sale of insulin in Norway. PMID- 2194319 TI - [To the memory of victims of Hitler's euthanasia program. Severe mental disorder as justification]. PMID- 2194320 TI - [Gram positive septicemia]. AB - There seems to be an increase in septicemia and the development of shock after infection by streptococci. Early diagnosis of serious streptococceal infection and intensive care of this group patients might prevent the onset of septic shock with its high morbidity and mortality. We illustrate the pathogenesis of serious streptococceal infection by three case reports, and discuss the pathophysiology and treatment of this serious infection. PMID- 2194321 TI - [Peroxisomal disorders. A new group of metabolic diseases]. AB - Peroxisomes play an essential role in a number of different metabolic reactions, and the last few years have seen an enormous increase in our knowledge about peroxisomes and peroxisomal disorders. These disorders are caused by impairment of one or more peroxisomal functions. This article briefly reviews the clinical and biochemical aspects of peroxisomal disorders. PMID- 2194322 TI - [Perinephritic abscess]. AB - In spite of technical advances in diagnostic radiology the recognition of a perinephric abscess is still a challenge to even the most experienced urologist. Untreated perinephric abscesses result in considerable mortality. We present ten years experience from 17 patients. All underwent open drainage procedures. In our case this still seems to be the treatment of choice for the majority of these patients. Percutaneous drainage is an alternative to surgery, and is particularly suitable for the high risk patient. PMID- 2194323 TI - [Bereavement, depression and immunity]. AB - Research on the relationship between bereavement, depression and immune function is reviewed with special regard to cellular immunity known to be important in the defence against virus infections and cancer. The results are ambiguous, but indicate reduced cellular immunity in connection with bereavement as well as serious depression. This reduced immunity is possibly more marked with increasing age. The author also discusses some methodological issues in psychoneuroimmunology. PMID- 2194324 TI - Acetaminophen-induced alterations in pancreatic beta cells and serum insulin concentrations in B6C3F1 mice. AB - Administration of acetaminophen (500 mg/kg) to male B6C3F1 mice resulted in alterations of pancreatic beta cell ultrastructure. These alterations were characterized by pronounced intercellular spaces, cytoplasmic vacuolization, damaged membranes of cytoplasm, secretory granules, and other organelles, and pyknotic nuclei with disrupted membranes. Concomitant with these changes, acetaminophen also caused increaes in serum insulin concentrations from 24 microU/ml at 0 time to 160 microU/ml at 8 hr and increases in serum alanine aminotransferase (ALT) concentrations from 42 to 13,279 U/liter, which indicated hepatic damage. Quantitation of 3-(cystein-S-yl)acetaminophen adducts in hepatic 10,000g supernatant protein using a particle concentration fluorescence immunochemical assay indicated a positive correlation between binding and the occurrence of the hepatotoxicity consistent with what has been previously reported; however, 3-(cystein-S-yl)acetaminophen protein adducts were not detected in pancreatic 10,000g supernatant. Immunohistochemical analysis of the liver and pancreas from acetaminophen-treated mice revealed acetaminophen-protein adducts in the centrilobular regions of the liver but not in the pancreatic islets. Doses of 100 and 200 mg/kg produced no evidence of hepatotoxicity and no increase in serum insulin; 300 mg/kg and higher doses produced both hepatotoxicity and increased serum insulin concentrations. A comparison of the time course for the increase in serum levels of ALT and insulin following a toxic dose of acetaminophen indicated that the increase in ALT preceded the increase in insulin. Thus the hepatotoxicity of acetaminophen correlates with the formation of 3-(cystein-S-yl)acetaminophen protein adducts in liver, which supports the concept that this toxicity is mediated by the reactive metabolite N-acetyl-p benzoquinone imine; however, the toxicity of acetaminophen to beta cells in the pancreas is apparently not mediated by this mechanism. PMID- 2194325 TI - Interaction of carbon tetrachloride with beta-naphthoflavone-mediated cytochrome P450 induction in winter flounder (Pseudopleuronectes americanus). AB - The interaction between beta-naphthoflavone induction (BNF: 100 mg/kg) and carbon tetrachloride (CCl4; 1 ml/kg) hepatotoxicity was examined in the flounder. Treatment groups composed of control, BNF, CCl4, and BNF/CCl4 were compared in terms of cytochrome P450 isozyme content (LM4b; LM2), catalytic activity, isozyme distribution. SGOT-SGPT levels, and pathology. CCl4 administration resulted in significant reductions in both the constitutive P450 (LM2) and the BNF-inducible isozyme (LM4b) as well as elevations in SGPT and SGOT levels. The decline in LM4b isozyme content was reflected by stoichiometric decreases in ethoxyresorufin-O deethylase activities. BNF/CCl4 coadministration was protective in part against CCl4 hepatotoxicity. Immunohistochemistry indicated that LM4b was diffusely distributed throughout the liver. These interactions have demonstrated a multiple P450 isozyme involvement, the protective nature of BNF against CCl4 hepatotoxicity in the flounder, the ability to maintain an inductive response in face of CCl4 coadministration, and the diffuse distributional pattern of LM4b in the flounder liver. PMID- 2194326 TI - [ROC-curve analysis. A statistical method for the evaluation of diagnostic tests]. AB - Receiver operating characteristic (ROC)-curves are a statistical method which may be employed inter alii for assessing a diagnostic test. These have been employed particularly in radiology but have also been employed for assessing laboratory tests and obstetric estiamation scales. The method is based on an analysis of nosological probabilities for varying limits of decision thresholds. ROC-curves may be employed for data on ratio/interval scales and data on rank scales. Parametric and non-parametric methods are available for obtaining a single quantitative measurement for the entire ROC-curve and to carry out significance tests between several ROC-curves. PMID- 2194327 TI - [Use of ketanserin in anesthesia. A selective S2 serotonin receptor antagonist]. AB - Serotonin is a vasoactive amine. It is formed in the chromaffin cells in the small intestine and is inactivated in the liver and lungs. The remainder is taken up in the thrombocytes so that only minimal quantities are found free in the plasma. The peripheral effect of serotonin occurs probably exclusively by means of a release of amine from the thrombocytes following local aggregation of these. Serotonin is thought to play a pathogenetic role in both systemic and pulmonary hypertension. Ketanserin is a serotonin antagonist with alpha-blocking effect. It reduces the blood pressure by reducing the peripheral vascular resistance without causing reflex tachycardia or fall in the minute volume of the heart. In the field of anaesthesiology, it may be employed in per- and postoperative hypertension but on account of the peripheral vasodilating effect it may also be employed in other conditions with peripheral vasoconstriction. Ketanserin has a moderate effect in cases of acutely developed pulmonary hypertension. PMID- 2194328 TI - [Inguinal paravascular block (3-in-1 block)]. AB - The three main nerves from the lumbar plexus may be blocked by injection of local anesthetic into the facial envelope of the femoral nerve ("three-in-one block"). The femoral nerve may be localized by obtaining paresthesia, by employing a nerve stimulator or by the loss of resistance technique. We prefer the use of a nerve stimulator. The "three-in-one block" may be employed for immediately pain relief of pain and for treatment of postoperative pain from fractures in the hip, femur and knee. Introduction of a catheter into the femoral nerve sheath is recommended to provide continuous block of the lumbar plexus for relief of postoperative pain. PMID- 2194329 TI - [Perioperative hypothermia in adults]. AB - In perioperative hypothermia, a central temperature of less than 36 degrees C develops in connection with anaesthesia and operation. Perioperative hypothermia constitutes a daily problem which results in increased morbidity and mortality in risk groups. The influence of anaesthetic agents on temperature regulation is reviewed. The postoperative hypothermic phase with increased oxygen requirement on rewarming increases the risk of development of complications, including cardiac complications. The risk groups and prophylactic methods for hypothermia are mentioned. Higher temperatures in the anaesthetic room, prewarming of infusion fluids and employment of infusion warmers should be employed with all anaesthetics. In patients in risk groups, extensive employment of combined methods of prevention of hypothermia is recommended. PMID- 2194330 TI - [Breast carcinoma in situ. Diagnostic and therapeutic aspects with special reference to growth patterns]. AB - The probability of developing in situ carcinoma has been calculated at about 25%, while the cumulative risk of having the diagnosis established is estimated at less than 1%. In situ carcinoma in its pure form constitutes up to about 6% of all newly diagnosed breast cancers in clinical series, whereas its share in the most thorough mammographic screening series ranges from 8 to 16%. This excess in diagnosis comprises, in particular, the ductal type, primarily its most aggressive forms. To-day in situ cancer occurs chiefly as non-palpable lesions demonstrated by mammography or as minor changes discovered accidentally by the pathologist. A more recent classification based upon histological growth patterns is described. The advantage of classifying according to growth pattern bears a good correlation to clinical presentation, extent of surgery and prognosis. The treatment of in situ carcinoma lacks a rational basis. Therapy should therefore be kept within the framework of prospective protocols. Various treatment modalities are described with reference to the most important multicenter trials. PMID- 2194331 TI - [Risk of high copper content in drinking water]. AB - Copper occurs in small amounts in certain food items, but toxic exposures in Northern Europe have occurred only in connection with contaminated drinking water. Chronic exposure of small children can result in development of Indian Childhood Cirrhosis. This disease has recently been documented in Germany as a result of drinking water contaminated from corrosion of water pipes made of copper. Continued diarrhoea in small children can also be due to high copper exposure. Copper is not routinely determined in drinking water in Denmark. Further, no central registration is available concerning water with low pH or the types of water pipes used in houses. PMID- 2194332 TI - [Renal effects of dopamine]. AB - Dopamine is an endogenic catecholamine which, in addition to being the direct precursor of noradrenaline, has also an effect on peripheral dopaminergic receptors. These are localized mainly in the heart, splanchnic nerves and the kidneys. Dopamine is produced in the kidneys and the renal metabolism is closely associated with the renal treatment of water and salt but the mechanism is not yet elucidated. In low doses (1-5 micrograms/kg/min), dopamine increases renal blood flow (RBF) and the glomerular filtration rate (GFR). In addition, pronounced diuretic and natriuretic effects are observed which are possible not exclusively secondary to alterations in the renal haemodynamics but may also be due to specific tubular effects. Recent investigations have revealed that dopamine does not increase RBF and GFR in patients with chronic renal failure if GFR is less than 60 ml/minute. Dopamine in low doses is frequently employed in cases of acute oliguric renal failure but the results available concerning the therapeutic effect are frequently retrospective and uncontrolled. The results suggest that early treatment with 1-3 micrograms/kg/min dopamine combined with furosemide can postpone or possibly render dialysis unnecessary in a number of patients on account of increased diuresis and natriuresis. The effect of GFR and the significance for the prognosis are not known. PMID- 2194333 TI - [Sickle-cell anemia and anesthesia]. AB - On account of immigration there are now groups in the Danish population, which should be tested for sickle-cell disorders before anaesthesia. In certain other countries patients of negro or arabian anchestry are sickle tested. Specific diagnosis of sickle-cell disorders is made only by haemoglobin electrophoresis. Sickle-cell crises are commonly precipitated by infection, dehydration, cold, hypoxia and acidosis. Before anaesthesia the patient must be free from intercurrent infection and well hydrated. During anaesthesia it is important to avoid hypoxia, hypotension, cold and venous stasis. Either general or regional anaesthesia may be used. Controlled oxygen therapy must be continued well into the postoperative period. PMID- 2194334 TI - [Infantile constipation and Allomin-lactulose. Treatment of infantile obstipation in infants fed with breast milk substitutes. A controlled clinical trial of 2 per cent and 4 per cent Allomin-lactulose]. AB - The Authors investigated the effects of Allomin with admixture of 2% and 4% lactulose on constipation in infants aged 0-6 months reared on breast-milk substitutes. The investigation was randomized and double-blind and was carried out during the period 1.4.1987-31.7.1988 on non-hospitalized infants in the counties of Funen and North Jutland in cooperation with the health visitors in these regions. Constipation was defined as hard and difficult defaecation and the trial period lasted for 14 days. Parents of the infants who participated classified the infants' motions according to consistence and degree of difficulty in defaecation on special forms. A total of 220 children participated and these received, after randomizing, either Allomin-lactulose 2% or 4% as the only breast milk substitute during the period of observation. The effect of treatment was defined as "no constipation" i.e. all motions during 24 hours described as easy and of normal or thin consistence. In addition, the effect was measured by the parents' general impression of what the infant thrived best on. With both of the preparations, treatment was effective in over 90% of the infants in both the groups without significant difference. The effect occurred gradually and, in some cases, up to 8-10 days after initiation of treatment without significant difference in the rate of effect between the groups. After the effect had commenced, significantly fewer thin motions occurred in the 2% group than in the 4% group. 92% of the infants in the 2% group and 91% in the 4% group wanted to continue the Allomin-lactulose preparation rather than the usual breast-milk substitute. A retrospective questionnaire to parents of 97 infants who had continued with Allomin-lactulose 2% was answered by 84.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2194335 TI - [Emergency ultrasonic examinations]. AB - The employment and yields of emergency examinations carried out outside normal working hours in Bispebjerg Hospital, Copenhagen, in 1987 are illustrated. This facility is employed particularly by surgical departments for examination of patients with acute abdominal and retroperitoneal conditions and it is frequently supplemented by immediate ultrasonically guided drainage. The possibility of emergency examinations contributed to rapid, certain and gentle diagnosis in the treatment of patients. PMID- 2194336 TI - Tissue response to mechanical vibrations for "sonoelasticity imaging". AB - The goal of "sonoelasticity imaging" is to differentiate between normal soft tissues and hard lesions. This is done by measuring and then displaying the ultrasound Doppler spectrum of regions within tissues which are mechanically forced with low frequency (20-1000 Hz) vibrations. The resolution and sensitivity of the technique ultimately rest on the spatial resolution of ultrasound Doppler detection, the low frequency mechanical properties of tissues, and the vibration response of layered, inhomogeneous regions with hard tumor inclusions and complicated boundary conditions set by the presence of skin, bones and other regions. An initial investigation has measured some tissue stiffness parameters, and applied these in a NASTRAN finite element analysis to simulate a prostate tumor in the pelvic cavity. The measurements show a wide separation between the elastic modulus of tumors and soft tissues such as muscle and prostate. NASTRAN analyses show the ability to delineate regions of different elasticity based on the pattern of vibration amplitudes. The ability to change vibration frequency within the 100-300 Hz band seems particularly helpful in simulations and experiments which visualize small stiff inclusions in tissues. Preliminary results support the postulate that sonoelasticity imaging can provide useful information concerning tissue properties that are not otherwise obtainable. PMID- 2194337 TI - Effects of transducer beam geometry and flow velocity profile on the Doppler power spectrum: a theoretical study. AB - A theoretical model is used to show how the Doppler spectrum for various axisymmetric velocity profiles is affected by beam misalignment and incomplete insonation. Results are presented for both circular and square beam geometries. Moreover, a closed-form expression is derived for the power spectral density received by an on-axis transducer with a Gaussian beam profile. It is shown that the error incurred in measuring the mean Doppler frequency with such a profile will generally be bounded by the results for the circular and square beam geometries. The effects of an ideal high-pass filter on the mean Doppler frequency and the backscattered Doppler power are examined. It is shown that such a filter can introduce large differences in the measured systolic to diastolic power ratios. Finally, theoretical expressions and results are presented for the spectral broadening index (SBI), normalized spectral variance (NSV), coefficient of kurtosis (CK), the coefficient of skewness (CS) as functions of the axisymmetric velocity profile shape assuming complete uniform insonation. PMID- 2194338 TI - Colour duplex ultrasound diagnosis of venous stenoses in renal allografts. PMID- 2194339 TI - Effect of selective tissue attenuation of pulsed Doppler frequency. PMID- 2194340 TI - Ultrasound in urology. PMID- 2194341 TI - Physical and technical foundations of diagnostic ultrasound. AB - The physical and technical foundations of investigations with diagnostic ultrasound are discussed. Two questions need to be answered: what is ultrasound, and how does an ultrasonic device operate? The mechanical properties of the human body are described by physical laws, such as the propagation of ultrasound waves, the interaction of ultrasound with tissue, attenuation, reflection, refraction, etc. Today high-technology ultrasonic devices are driven by computers. Imaging of the same kidney with different devices shows the progress made in image quality over a period of about 15 years. Details of tissue and biometry are largely enhanced. Powerful tools allow different forms of precise analysis of online measurements. Advanced handling of information gives further opportunities to image processing. The final question is the extent to which the physician and surgeon want to work with such as sophisticated high-technology imaging system and learn to manage its hard- and software. PMID- 2194342 TI - Ultrasonography of the retroperitoneum. AB - Ultrasonographic investigation of the kidneys and efferent urinary tract as well as juxtarenal organ regions has become an indispensable screening method in urology today. Various diseases of the kidneys can be detected rapidly and noninvasively. Some of these clinical pictures are discussed in detail. Above and beyond simple imaging, ultrasonography also allows special diagnostic interventions (biopsy) and therapeutic measures (i.e. nephrostomy). PMID- 2194343 TI - Ultrasound examination of bladder and prostate. AB - Transabdominal (suprapubic) sonography of the bladder and prostate is not limited to special indications but should be considered an integrated part of the urologic sonographic evaluation of the genitourinary tract. Information about many pathological conditions (e.g. residual urine, stone, tumor, diverticulum, enlarged prostate) is obtained without delay, without need of instrumentation or exposure to X-rays. Transurethral sonography has proven useful in the differentiation of superficial bladder tumors from deep infiltrating ones. Transvaginal or transrectal examination of the bladder neck has developed into a new modality for urodynamic examination. More than any other diagnostic modality, transrectal ultrasound of the prostate has become a valuable tool for the more correct detection and staging of prostatic carcinoma. PMID- 2194344 TI - Scrotal sonography. AB - During the last 10 years, sonography has become an essential examination in establishing the diagnosis of urological diseases. The use of high frequency real time probes makes the visualization of superficial organs easy. Sonography is a valuable method for distinguishing an intrinsic testicular lesion from an extrinsic one. But, it is not always possible to perform a differential diagnosis between a vascular or an inflammatory process in an equivocal clinical situation. Color Doppler sonography is a system which combines conventional real-time sonography with real-time two-dimensional Doppler imaging. Thus, at the same time, it offers the possibility of viewing the lesion and checking the organ's vascularization. Our first clinical experience with this new device is presented. PMID- 2194345 TI - Interventional sonography in urology. What makes ultrasound so useful? AB - Nephrostomy is probably the most common percutaneous ultrasound-guided intervention. Since it is the basis for access to the collecting system of the kidney, the technique is described in detail. Other forms are diagnostic pyelopuncture and antegrade stenting. Percutaneous surgery requires dilatation of the tract upon puncture in order to introduce instruments for litholapaxy, splinting strictures (endopyeloplasty) or tumor resection. Retroperitoneal accumulations of fluid outside the collecting system can be drained under sonographic view. Ultrasound is further used to localize solid structures (kidney, renal tumor, lymph nodules, prostate) for biopsy. PMID- 2194346 TI - Ultrasonic Doppler and duplex systems: possibilities and limitations. AB - In order to utilize Doppler modalities in an optimal manner, one should both be aware of their potential and respect their limitations. To this end, a variety of technical and physical factors affecting the performance of Doppler devices are discussed: (1) the velocity of propagation limiting the temporal resolution of pulsed systems; (2) intervening tissue that may weaken the echo considerably; (3) the size of the sample volume that could be too small to provide a transvascular mean velocity or too large to discriminate flow in adjacent vessels; (4) the principles of continuous wave mode lacking depth resolution, and pulsed mode being prone to aliasing; (5) the additional complexity of duplex/triplex systems; (6) the tight temporal restrictions of 2-dimensional color mappers which cause poor velocity resolution, and (7) the angle of incidence that needs to be assessed in order to measure absolute velocity and the cross-sectional area that must be measured additionally for the calculation of the volume flow rate. Based on this discussion, some hints on selecting instruments or instrument parameters are given. PMID- 2194347 TI - Importance of Doppler sonography in urology. AB - There have been major advances in Doppler technology over the last 5 years which are particularly useful in the field of urology. In the early 1980s the clinical significance of Doppler was limited to the diagnosis of testicular torsion and its use was primarily intraoperative. Today, however, new advances, i.e. pulsed Doppler, duplex sonography, and color-coded duplex sonography (angiodynography), have cleared the way for totally new approaches to vascular impotence, renal artery stenosis, renal artery embolus, intratumor flow measurement, and control of renal transplants. These new technical advances will be exemplified in typical pathological states. PMID- 2194348 TI - Qualitative tear film disease. AB - Abnormalities of the lipid and mucin components of the preocular tear film may result from diseases of the eyelid margins and conjunctiva. Chronic keratoconjunctivitis with epithelial edema and superficial corneal neovascularization, with or without ulceration, characterizes qualitative tear diseases. Tear components other than lipid and mucin that carry probable clinical significance include tear proteins, all-trans retinal, cholesterol, glucose, and electrolytes. Although less common than quantitative or aqueous deficiencies, qualitative abnormalities are recognized as primary or secondary causes of ocular surface disease in companion animals. PMID- 2194349 TI - A new perspective on canine keratoconjunctivitis sicca. Treatment with ophthalmic cyclosporine. AB - Keratoconjunctivitis sicca is the major cause of chronic or recurrent conjunctivitis in dogs. The diagnosis of KCS is often delayed or mistaken for allergic or bacterial conjunctivitis and inappropriate or insufficient treatment leads to progressive corneal scarring and blindness in many dogs. The cause of KCS in dogs has not been proven, but evidence supports an immune-mediated etiology for the majority of cases. In an attempt to specifically treat the cause of KCS, a new immunosuppressant drug, cyclosporine, has been used in a topical preparation. Treatment results using ophthalmic cyclosporine are dramatic compared with historical treatments. Resolution of corneal scarring and increased lacrimation are seen in most dogs. Investigations of the mechanism of action of ophthalmic cyclosporine suggest the efficacy may have been serendipitous. A local neuroendocrine effect of cyclosporine on the lacrimal gland may actually be responsible for the increased lacrimation. Early diagnosis of KCS and treatment with ophthalmic cyclosporine may avert a major cause of blindness in dogs. PMID- 2194350 TI - Microbiology of the canine and feline eye. AB - Knowledge of the microbiology of the canine and feline eye in normal and pathologic states is an important aspect of the clinician's assessment of external ocular disease. Gram-positive bacteria predominate in surveys of microbial flora in normal and diseased eyes. These same organisms are routinely isolated from skin and the upper respiratory tract. Injury to the eye may result in proliferation and potential pathogenicity of normal ocular flora. A variety of bacterial, fungal, viral, and other microbial isolates affect the diagnosis and treatment of external ocular disease. PMID- 2194351 TI - Persistent corneal ulcers. What to do when ulcers won't heal. AB - Persistent corneal erosions may be primary or secondary to a variety of ocular diseases such as KCS, infection, or adnexal disease. Primary corneal diseases that may result in nonhealing erosions include corneal EBMD and endothelial dystrophy or degeneration. The challenge that the practitioner faces is to differentiate between them and to apply the appropriate treatment. A variety of medical and surgical therapies are at the disposal of the practitioner. These include debridement, contact lens placement, superficial keratectomy, punctate keratotomy, hyperosmotic solutions, and several new drug modalities such as epidermal growth factor, fibronectin, and aprotinin. PMID- 2194352 TI - Ulcerative keratitis. AB - Ulcerative keratitis comprises an important proportion of presenting ocular complaints in small animals. Because of its high frequency, corneal ulceration may not routinely stimulate the clinical concern for rigorous diagnosis, attentive management, and aversion of potential complications that it merits. Only by maintaining an appreciation for the pathologic processes at work during corneal injury and repair can busy clinicians competently diagnose, successfully treat, and forestall the complications of corneal ulceration. PMID- 2194353 TI - Corneal dystrophy in the dog and cat. AB - Two types of epithelial dystrophy have been described in dogs, one each in the Boxer and Shetland Sheepdog breeds, both of which can be associated with corneal erosions. Medical therapy is recommended when erosions or tear film abnormalities are present. Stromal dystrophies documented in dogs appear to be a primary lipid deposition in various layers of the stroma, depending on the breed. Stromal dystrophies seldom lead to loss of vision, but vision loss has been observed in middle aged Airedale Terriers and aged Siberian Huskies. Treatment is usually unnecessary. The dog demonstrates two types of endothelial dystrophy, one of which (posterior polymorphous dystrophy in the American Cocker Spaniel) does not lead to corneal edema. Endothelial dystrophy observed in the Boston Terrier, Chihuahua, and other breeds is associated with progressive corneal edema, which can lead to bullous keratopathy and corneal erosions. Stromal and endothelial dystrophies, both of which are associated with rapid progression of corneal edema, occur rarely in the cat. Treatment of dystrophies with progressive corneal edema is symptomatic and palliative. PMID- 2194354 TI - Control of ocular inflammation. AB - Although both topical and systemic anti-inflammatory agents have a place in veterinary ophthalmology, they play only a small role in overall patient management. They must be used appropriately to prevent ocular damage and loss of vision from inflammation and are not a replacement for a complete ophthalmic examination and specific treatment directed at the etiology of the problem. If used indiscriminately, they can result in local or systemic side effects or toxicities, many of which are worse than the initial problem for which they were selected. Just as topical corticosteroids are contraindicated with infectious keratitis, so are systemic corticosteroids contraindicated in patients with ocular inflammation resulting from a systemic infectious process. Anti inflammatories must be used at the appropriate dosage and frequency. Use of corticosteroids that have low intraocular penetration for intraocular disease or corticosteroids with low potency is a waste of time and money. The most expensive medication is one that does not work. Avoid combination therapies when only a single medication is required. These do not save time or money and have the potential to result in the development of drug-related diseases. Diseases for which anti-inflammatory therapy has little or no indication include corneal scars, corneal edema, corneal pigmentation, corneal dystrophy, cataracts without inflammation, glaucoma, and retinal atrophy and degeneration. Last, remember that all commercially available ophthalmic medications are specifically formulated for use in the eye. Their pH, concentration, osmolality, and melting temperature all are designed to facilitate penetration. The use of dermal and otic preparations to treat ophthalmic problems is contraindicated. PMID- 2194355 TI - Uveitis in the dog and cat. AB - Uveitis, inflammation of the vascular middle coat of the eye, may be a common manifestation of several diseases. Clinical signs of uveitis include ocular discharge, redness, and pain. Uveitis should be differentiated from other conditions causing similar clinical signs. Once uveitis is recognized, attempts to identify a specific cause should be undertaken. In some cases, an underlying cause is not identified, and treatment is aimed at preventing additional ocular damage. PMID- 2194356 TI - Cataract surgery. Current approaches. AB - Cataract surgery in the dog can be a highly successful and rewarding technique for restoring vision to the cataract patient. Coexisting ocular conditions can complicate cataract surgery or be a contraindication for lens removal; these include KCS, uveitis, glaucoma, lens subluxation, and retinal disease. Techniques for cataract surgery include intracapsular cataract extraction, extracapsular cataract extraction, and phacofragmentation, both extracapsular and endocapsular (intercapsular). Phacofragmentation is probably the most successful technique in the dog at this time. Postoperative complications include uveitis, hyphema, glaucoma, capsular opacities, corneal endothelial damage, and retinal detachments. Newer methods of dealing with these problems include the use of viscoelastic materials and IOL implants intraoperatively and the use of the Nd:YAG laser for posterior capsulotomies postoperatively. PMID- 2194357 TI - Lens luxation in the dog and cat. AB - Dislocation, or luxation, of the lens arises as a result of rupture of the zonular fibers, which suspend the lens from the ciliary body. In the dog, lens luxation is most frequently encountered as a primary, heritable condition in which there appears to be an inherent weakness of the zonule. The condition is limited mainly to the Terrier breeds but has also been described in the Tibetan Terrier and Border Collie. The disease is essentially bilateral but seldom becomes apparent clinically before 3 or after 7 years of age. In most primary luxations, the lens passes into the anterior chamber and such cases must be regarded as emergencies on account of the likely development of secondary glaucoma; posterior luxations are usually less troublesome. Other causes of lens luxation include cataract formation, glaucoma, and uveitis. Congenital dislocations and those attributable to trauma alone are rare. In the cat, lens luxations are usually secondary and arise in later life. PMID- 2194358 TI - Glaucoma in the dog and cat. AB - Conjunctivitis, mydriasis, corneal edema, lens luxation, buphthalmos, and blindness are caused by elevated IOP in the glaucomas. Primary glaucomas with a bilateral potential for development are noted in two cats and several dog breeds, with secondary glaucomas caused by uveitis and neoplasia common in the cat and dog. Tonometric evaluation is essential for the early diagnosis and management of glaucoma. Medical therapy of topical demecarium bromide and timolol maleate, with systemic dichlorphenamide, are recommended for general glaucoma maintenance therapy in dogs and cats. Transcleral cyclophotocoagulation will surgically reduce IOP in cases in which maximum medication has been reached. PMID- 2194359 TI - Retinal degeneration in the dog and cat. AB - Retinal degenerations in the dog and cat are an important cause of blindness in these species. Particularly in the dog, many retinal degenerations, collectively called progressive retinal atrophy, seen in clinical practice are inherited. The clinical signs, electrophysiological findings, pathology, and underlying biochemical defects in the retina vary from breed to breed. Specific categories of inherited retinal degeneration are now recognized, and classified into early onset photoreceptor dysplasias, late-onset retinal degenerations, or retinal degenerations secondary to primary RPE dystrophy. As new inherited retinal degenerations are reported in different breeds they can generally be assigned to one these categories. Other causes of retinal degeneration include nutritional deficiencies, glaucoma, inflammation, ischemia, and toxins. Idiopathic retinal degeneration occurs in the dog with some frequency. PMID- 2194360 TI - Ocular neoplasia in small animals. AB - Important and rare primary tumors of the globe of dogs and cats are discussed with particular emphasis on biological behavior and morphologic features that predict biological behavior. Classification systems currently thought to be most useful for predicting the behavior of canine and feline ocular melanomas are emphasized. The recently described feline posttraumatic ocular sarcoma is discussed. PMID- 2194361 TI - Ocular manifestations of systemic disease in the dog and cat. Recent developments. AB - The number of canine and feline clinical diseases that may be manifested as ocular dysfunction continues to increase. Veterinarians are often presented with sick patients who also have eye disease. Conversely, animals are examined for eye disease that on closer inspection also have a systemic illness. A decision must be made; is there a relationship between the observed ocular and systemic problem, or are they separate morbid processes? If they are related, can the ocular signs be used to better define the systemic illness, chart its course, or establish a prognosis? It is hoped this article will aid the clinician in gaining a better perspective on the complex relationship between the eyes and systemic disease. PMID- 2194362 TI - Host defence and bovine coliform mastitis. Host defence mechanisms and characteristics of coliform bacteria in coliform mastitis in bovine: a review. AB - This paper reviews the microbial properties that underlie the virulence of coliform microorganisms causing bovine mastitis. The interaction between the coliform bacteria and teat-duct defence, humoral defence and phagocytic cells is discussed. The functioning of these host-defence mechanisms seems to exert a major role in the course of a coliform infection of the udder. PMID- 2194363 TI - The indirect fluorescent antibody test for bovine anaplasmosis. AB - An indirect fluorescent antibody test was used successfully for the serodiagnosis of experimental Anaplasma infections in cattle. Specific antibodies were detected three to ten days after anaplasma bodies were found in the blood, and persisted at least 15 weeks post-infection. An American and an African stock of A. marginale were used to prepare antigens, and gave comparable results when tested on sera positive to either of these stocks, as well as to an A. central-like stock from Korea. There were no cross-reactions with several Theileria, Babesia, Trypanosoma and Eperythrozoon species. PMID- 2194364 TI - Measurement of protease thermostability, twitching motility and colony size of Bacteroides nodosus. AB - Total extracellular protease activity of Bacteroides nodosus in TAS liquid culture varied directly with cell mass and buffer concentration between 20 and 50 mM HEPES, MOPS and TES buffers, but not with Tris which gave anomalous high cell counts, nor with Na2Co3 which showed a decline of protease activity and cell mass. The stability of HEPES-buffered crude protease preparations were estimated on the basis of temperature or Ca2+ activity. Variation of the estimates for cellular twitching was greater than that for colony diameter in benign and virulent strains of B. nodosus. Surface translocation, quantified on the basis of colony diameter, reached a limit after 72 h incubation on modified TAS agar, ranging from 0.04 to 0.14 mm per h for six isolates tested. PMID- 2194365 TI - [The effect of antioxidants on the balance of proteinase-inhibitors system in the respiratory space of mice with pulmonary tuberculosis]. AB - In three series of experiments generalized form of tuberculosis was simulated in 427 mice of CBA strain. After dissection of chest bronchoalveolar lavage was carried out and in the fluid obtained total content of protein, elastase-like and antitryptic activities were estimated. At the severe stage of the disease content of protein was increased 7-fold, antitryptic activity--5-fold and elastase-like activity--10-fold in the lavage. EDTA did not inhibit the elastase-like activity, i.e. the enzyme was derived only from neutrophils. All the patterns studied were unaltered after the animal treatment with alpha-tocopherol at a dose of 100 mg/kg (per os) within one or three weeks. In vitro incubation of preparations in presence of ascorbic acid at the final concentration of 0.01 M within 1 hr at 37 degrees caused a considerable (4-6-fold) activation of the antitryptic activity simultaneously with a distinct decrease in the elastase-like activity down to physiological values. The data obtained suggest that inactivation of the reactive centre of antiproteinases by means of products of free-radical oxidation appears to be mainly responsible for disbalance of proteinases-inhibitors in tuberculosis. PMID- 2194366 TI - [Activity of proteolytic enzymes and their inhibitors in large intestine tumors]. AB - Activity of proteolytic enzymes and their inhibitors was studied in malignant and benign tumors of large intestine from 133 patients. Activity of proteinases was distinctly higher in malignant tumors as compared with unaltered tissue, while in benign tumor the enzymatic activity was similar to that of unaltered tissue. Inhibitor of proteinases exhibited lower activity in malignant tumor as compared with unaltered tissue and benign tumor. After irradiation treatment of tumors activity of the proteinases inhibitor was practically unaltered, while the enzymatic activity was distinctly decreased. PMID- 2194367 TI - [Glycosylated lipoproteins as atherogenic factor in diabetes (review of the literature)]. AB - Data on the role of glycosylated lipoproteins in atherogenesis are reviewed. Posttranslational modification of proteins involving nonenzymatic glycosylation occurred under conditions of normal state but the highest rate of these reactions was found in hyperglycemia (diabetes). Glycosylation, after blocking of the epsilon-amino group in lysyl residue in protein moiety of lipoproteins, transformed distinctly the physico-chemical and metabolic properties of apoproteins, as a result of which normal catabolism of lipoproteins was impaired. Reactions of glycosylation are mainly responsible for pathogenetic interrelationship between diabetes and atherosclerosis. Glycosylation of lipoproteins may contribute to development of atherosclerosis via autoimmunity mechanisms. PMID- 2194368 TI - [Characteristics of elastin from the wall of human large arteries during treatment with formaldehyde]. AB - Biochemical studies of elastin from human large arteries wall were carried out using both native and treated with formaldehyde protein. No differences were observed in sensitivity of native and formaldehyde treated elastin to the effect of various proteases and to alkaline-alcohol hydrolysis. Fractions obtained after enzymatic and alkaline hydrolysis were similar in their composition. PMID- 2194369 TI - [Liposomes in experimental virology]. PMID- 2194370 TI - [Comparison of 3 express-methods of detection of tick-borne encephalitis virus]. AB - Comparative studies of the diagnostic value of three express methods for detection of tick-borne encephalitis virus in ticks (fluorescent antibody technique (FAT) enzyme immunoassay (EIA), and molecular hybridization of nucleic acids) and the traditional method (bioassay in white mice) showed all the three express methods to be rapid, specific, sensitive, and useful for large-scale epidemiological surveys. Notable was the high effectiveness of the method of nucleic acids hybridization which was not inferior to bioassays in suckling mice and exceeded FAT and EIA. The results of the latter seem to be affected by antigenic variations among tick-borne encephalitis virus strains. PMID- 2194371 TI - [A rapid isolation of Venezuelan equine encephalomyelitis virus using the lanthanide immunofluorescence assay]. PMID- 2194372 TI - Mountain sickness. AB - Acute mountain sickness (AMS) is a failure to adapt to high altitude. Although some people may be at increased risk, most cases are unpredictable. Much can be done, however, to prevent AMS or limit its severity. Staging ascent, sleeping low, and avoiding overexertion and respiratory depressants are all helpful. For some, drug prophylaxis should be considered. Treatment is based on clinical severity, with descent remaining the primary treatment for severe cases. PMID- 2194373 TI - Florence Nightingale--the social construction of a Victorian feminist. PMID- 2194374 TI - [Status and trends in locoregional chemotherapy]. AB - The idea to increase the cytostatic concentration by direct perfusion of the target organ and to simultaneously reduce the systemic side effect is almost 40 years old. New techniques brought new impulses to this old method, namely regional chemotherapy, by the discovery of a fully implantable catheter system as a byproduct of space research. This system can be used intravenously, intraarterially and intraperitoneally. In addition to avoid some types of complications caused by externally placed catheters this system serves another important goal in palliative cancer treatment: an improved quality of life, as a good ambulatory implementation is secured. PMID- 2194375 TI - [Importance and problems of intraperitoneal chemotherapy]. AB - Intraperitoneal chemotherapy for prophylaxis and treatment of peritoneal carcinosis is a new treatment modality. Due to a very difficult definition of remission for peritoneal carcinosis, results of this treatment modality are difficult to state. The total remission rates are currently between 30 and 50% in minimal residual disease. The major advantage of intraperitoneal chemotherapy is the augmentation of the local concentration of the cytotoxic agent which exceeds the serum level in some cases by a factor of 1000. Due to totally implantable systems the high risk of infection in patients with Tenckhoff catheters could be reduced to nearly zero. After perfusion of the peritoneal cavity with a cytotoxic agent the concentration in the portal vein can exceed that in the peripheral blood by a factor of 10. Results of two adjuvant trials could not show a survival benefit of treated patients, however the incidence of peritoneal carcinosis was significantly decreased. New treatment options are a perfusion of the peritoneal cavity with effective cytotoxic drugs in the very early postoperative time period. The combined treatment of cytostatics and "biological response modifiers" could further increase the effectiveness of this treatment modality. PMID- 2194376 TI - [Radio-oncological treatment possibilities in local recurrence of rectal carcinoma. An interdisciplinary comparison]. AB - Local recurrences of rectal carcinomas are frequently associated with a considerable morbidity and a dismal prognosis. Surgical resection leads to long term tumor control in about 30 to 40%, but surgery can be offered to only 10 to 30% of the patients. Cytotoxic chemotherapy is able to induce local responses in 15 to 40% of the cases--similar figures as achieved by radiation therapy alone. A pilot study is presented using radiation therapy combined with the sensitizing agent razoxane (ICRF 159). There was an objective response rate of 62% and the median survival rose to 24 months (13 months with radiation therapy alone). These data compare almost to results seen in surgical series. However, they need confirmation. PMID- 2194377 TI - [Experiences with a new second-line protocol in the treatment of pretreated and advanced Hodgkin disease]. AB - Between 1983 and 1987, we treated 16 patients with Hodgkin's disease, according to a post-COPP and a post-ABVD protocol, respectively. All patients had received previous treatment, including megavoltage cobalt radiotherapy, and were in advanced stages of disease, mostly with immunosuppression/immune deficiency. The protocol of lomustine, etoposide, adriamycin, methotrexate and prednisolone was commenced after the above therapy had failed or was not tolerated. Compared to the previously used chemotherapy, the 3 new cytotoxic agents were well tolerated. A complete remission was obtained in 4 patients and a partial remission in 9. In 2 patients, there was a temporary partial remission only. In more than half the patients, a positive effect on the clinical course was recorded. Viewed as a whole, a favourable objective and subjective result ensued. This LEAMP second line protocol was found to be effective and well tolerated. PMID- 2194378 TI - Role of epidemiology in vaccine policy. AB - The application of epidemiological techniques is important at all stages in the development of a vaccination programme. Before licensing, the safety and efficacy of a new vaccine must be determined in carefully designed clinical trials. An epidemiological assessment of the disease is then needed in order to formulate an appropriate strategy for delivery of the vaccine. Once the vaccine has been introduced into routine use, continued evaluation, both of the vaccine and the programme, is required. Surveillance schemes should be established that are capable of detecting changes in vaccine safety and efficacy as well as monitoring coverage in the target population. Any important changes should be further evaluated by special studies. Postlicensing evaluation of vaccines and vaccination programmes has played an important role in shaping policy in the UK. PMID- 2194379 TI - Yeast-derived hepatitis B vaccine in dental students. A three-year follow-up study. AB - Sixty health adults (56 dental students and four post-graduates of the Dental Faculty in Milan; mean age 26.4 years, range 22-42 years) were vaccinated with a recombinant DNA vaccine (Engerix B, Smith Kline and French; 20 micrograms given i.m. at time 0, 1 and 6 months). One month after the third injection, 98.3% (59/60) vaccinees showed anti-HBs at levels higher than 10 mIU ml-1 (geometric mean titre 734.8 mIU ml-1). One year after the beginning of vaccination (i.e. 6 months after the third injection of vaccine), 46 vaccinees showed anti-HBs titre higher than 100 mIU ml-1 (24 between 100 and 1000 mIU ml-1 and 22 higher than 1000 mIU ml-1) and 14 vaccinees had anti-HBs below 100 mIU ml-1 (12 between 10 and 99 mIU ml-1 and 2 below 10 mIU ml-1). Since duration of antibody is directly related to the height of the initial response, the 14 vaccinees with lower anti HBs titres were given a fourth dose of vaccine. All boosted vaccinees showed a vigorous anti-HBs response and the post-booster anti-HBs GMT increased to 1570 mIU ml-1 compared with 47.8 mIU ml-1 attained before the boosting injection. At three years from the beginning of vaccination, all vaccinees who showed anti-HBs titres higher than 100 mIU ml-1 after the primary vaccination and all but one of the boosted vaccinees were still anti-HBs positive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2194380 TI - Effect of live attenuated, cold recombinant (CR) influenza virus vaccines on pulmonary function in healthy and asthmatic adults. AB - The effects of intranasal inoculation with live attenuated, CR influenza virus vaccines on pulmonary function in healthy and asthmatic adults were evaluated in placebo-controlled, double-blind studies. In 46 healthy adult volunteers, there were no statistically significant alterations in pulmonary function as measured by spirometry and histamine bronchoprovocation tests in the first week following monovalent CR influenza virus vaccine [type A (H3N2, H1N1) and type B]. Among healthy adults with pre-inoculation PC20s less than 10 mg ml-1, 8/12 were infected following vaccination but no significant alterations occurred in histamine bronchoprovocation. In 11 asthmatic adults, no statistically significant alterations in pulmonary function, as measured by spirometry, were noted during the first 7 days postinoculation with bivalent CR influenza virus vaccine type A (H3N2 and H1N1). Postinoculation respiratory illnesses were more common in CR influenza virus vaccine recipients than placebo recipients, but they were mild, consisting of afebrile pharyngitis and transient rhinorrhea. Attenuated CR influenza virus vaccines do not appear to impair pulmonary function during the first week following immunization of healthy and asthmatic adults. PMID- 2194381 TI - Stable Salmonella live vaccine strains with two or more attenuating mutations and any desired level of attenuation. AB - Mutants optimally attenuated for highly susceptible hosts and protecting after a single oral vaccination are often overattenuated for host species being less susceptible. Therefore, to select vaccine strains optimally attenuated for the particular host species it is essential that a range of mutants with graded levels of attenuation be provided so as to permit lesser susceptibility to be compensated for by a correspondingly lower level of attenuation. This, while guaranteeing the stability through two-marker or multi-marker attenuation, can be suitably accomplished by slightly to moderately virulence-reducing mutations. Aspartic acid auxotrophy and, in particular, 'metabolic drift' mutations, possibly by additionally incorporating antiepidemic markers, are adopted for the mouse model to demonstrate stepwise production of S. typhimurium and S. typhi vaccine candidate strains with graded attenuation or any level of attenuation desirable. It is emphasized that this basic approach is relevant to practice. PMID- 2194383 TI - Collision course. PMID- 2194382 TI - Cocaine: recognizing, treating the abuser. PMID- 2194384 TI - [They rotate workplaces and maintain scope in the job]. PMID- 2194385 TI - [Occupational factors in spontaneous abortion]. AB - Occupational factors in spontaneous abortions are reviewed and discussed in terms of difficult working conditions (physical and psychological strains) and exposition to noxious agents in women and men. The discussion was based upon clinical, epidemiological and biological studies. The results showed elevated abortion risks in different occupational groups. Risk factors for both partners were hard physical work, psychological and socio-economic stress, some chemicals, metals and pharmacological products. Animal studies demonstrated time- and dose dependent effects on embryonic and fetal development as well as accumulation and potentiation of teratogenic agents. Chronic and multifactorial occupational effects seem to be very important and need further occupational effects seem to be very important and need further study. PMID- 2194386 TI - [Ovulation induction using clomiphene conversion]. AB - 20 anovulatory and clomiphene resistant patients had been treated by the so called clomiphene conversion. Pregnancies could be achieved in 6 women. 7 further patients reacted by ovulation. In selected cases the clomiphene conversion may be an alternative of therapy with gonadotrophins and GnRH pulsatile. PMID- 2194388 TI - Review: sodium fluoride: too late and too toxic for the elderly osteoporotic patient? PMID- 2194387 TI - Smoking prevention among people aged 60 and over: a randomized controlled trial. AB - This study aimed to test the hypothesis that people aged 60 and older respond to assistance in stopping smoking. Using a single general practitioner visit backed up by a practice nurse, 14% of the smokers had discontinued the habit 6 months after the intervention period. The intervention group also showed some improvements in a standardized measure of breathlessness. PMID- 2194389 TI - The Journal celebrates its diamond anniversary: a remarkable record of achievement. PMID- 2194390 TI - Thermal debracketing of orthodontic resins. AB - Ten commercial brands of orthodontic bonding materials representing three modes of delivery systems (two-paste, no-mix, and powder/liquid) were used to bond stainless steel brackets to bovine teeth. Heat was applied to the bracket, and the temperature at debonding was noted for each type of resin. The two-paste systems required a higher temperature to debond than did the no-mix systems. The powder/liquid system required the lowest temperature. There is a direct relationship between filler content and debonding temperature. There is an inverse exponential relationship between debonding temperature and load needed to cause debracketing. Room-temperature debonding showed failure at the bracket/resin interface with evidence of cohesive enamel fracture. Thermal debonding showed no evidence of overt enamel fracture, and failure site shifted toward the tooth/resin interface. Ceramic brackets required almost twice the time to debracket than did stainless steel brackets. PMID- 2194391 TI - The shear bond strengths of stainless steel orthodontic brackets bonded to teeth with orthodontic composite resin and various fissure sealants. AB - Enamel decalcification (whitened areas) around orthodontic brackets during therapy is a well-recognized problem. If a fissure sealant could be used to isolate the enamel and yet withstand debonding of the bracket during therapy, this problem might be overcome. The objective of this in vitro study was to determine (1) the shear bond strengths of stainless steel orthodontic brackets bonded to teeth with an orthodontic bonding resin together with a primary coating of various fissure sealants and (2) the fracture sites of these debonded samples. Forty noncarious human canine teeth were divided into four groups of 10 teeth each. In group A, the brackets were bonded to the buccal surfaces of the prepared teeth with a macrofilled orthodontic composite resin only. In groups B, C, and D, the brackets were similarly bonded, except that the teeth were first treated with a fissure sealant--group B having a light-cured unfilled clear fissure sealant, group C having a light-cured microfilled fissure sealant, and group D having a chemically cured opaque fissure sealant. After storage at 37 degrees C for 24 hours, the brackets were subjected to a shear force in an instron machine, and the fracture strengths were recorded, together with the sites of fracture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2194392 TI - Further characterization of prolymphocytic leukemia cells as a tumor of activated B cells. AB - Peripheral blood mononuclear cells from 24 patients with prolymphocytic leukemia (PLL) were isolated using a Ficoll-Hypaque gradient and stained by indirect immunofluorescence using a wide panel of monoclonal antibodies against B cell restricted and associated antigens, including HLA DR (Ia), CD19, CD21 (C3dR) surface membrane immunoglobulin (Slg), CD10 (CALLA), C3b, B5, CD25 (TAC), PCA1, T9, and T10. The cells were also tested for the FMC7, defined previously on PLL cells and the RAB1, a newly described hairy cell leukemia antigen. Thirteen out of the 24 samples expressed with variable intensity all the above antigens. While Ia, CD19, CD20, FMC7, and RAB1 were strongly or moderately expressed in all, the complement receptors (CD21 and C3b) were only weakly expressed in 12 cases; and the activation antigens B5, TAC, T9, T10, and PCA1 were found with variable intensity in two-thirds of the cases. In 50% of the cases tested, the CD5 antigen (usually strongly expressed on B CLL cells) was weakly to moderately expressed. These findings (absence or weak expression of complement receptors with variable expression of activation antigens) suggest that the PLL cells are activated B cells. When stimulated in vitro by anti-mu and TPA, (phorbol ester) tumor cells showed a decrease in CD21 and Slg and a stronger expression of CD25, T9, T10, and PCA1, with evidence of Ig secretion in four out of the seven cases studied. This confirms that the PLL cells arrested at an advanced stage of differentiation progressed narrowly to more differentiated cells. In view of our findings, we believe that the term prolymphocytic leukemia is inaccurate to define the stage of cell differentiation, and we suggest calling the disease preplasmacytic leukemia. PMID- 2194393 TI - Familial adult T-cell leukemia/lymphoma. AB - Clinical and laboratory data are described for two siblings who both developed adult T-cell leukemia/lymphoma resulting from infection by human T lymphotropic virus type I (HTLV-I). These findings suggest that genetic factors or virus specific factors may determine which HTLV-I-infected individuals will develop leukemia. PMID- 2194394 TI - Proximal interstitial deletion of 7q: a case report and review of the literature. AB - A male infant with multiple congenital anomalies was found to have a deletion of 7q [46,XY,del(7)(pter----q11.2::q22----qter)]. The father had a balanced rearrangement involving chromosomes 7 and 9, interpreted as 46,XY,dir ins(9;7), (9pter----9p12::7q22----7q11.2::9p12----++ +9qter;7pter---- 7q11.2::7q22--- 7qter). C-banding showed that the rearrangement occurred as a new event in the paternal grandfather's germ-line. Including the present patient, 16 cases of proximal 7q deletion (q11----q21/q22) have been described to date. This is a sufficient number of cases to permit comparison of manifestations to attempt delineation of karyotype-phenotype relationships in different proximal interstitial deletions of 7q. PMID- 2194395 TI - Genetics of conotruncal malformations: review of the literature and report of a consanguineous kindred with various conotruncal malformations. AB - Genetic predisposition in congenital heart disease is considered to be a component of multifactorial inheritance. Recently, monogenic inheritance in conotruncal malformations has been suggested. We describe a consanguineous kindred with various conotruncal malformations, the presence of which lends support to the idea that this spectrum of malformation is monogenically inherited. Theoretical background and experimental and clinical data are reviewed and discussed. PMID- 2194396 TI - The work of getting well. 1969. PMID- 2194397 TI - A microtiter plate assay for aspartate transcarbamylase. AB - A discontinuous, colorimetric method for the assay of aspartate transcarbamylase has been adapted for use with 96-well microtiter plates. The method is based on that of L.M. Prescott and M.E. Jones (1969 Anal. Biochem. 32, 408-419) for the detection of ureido compounds, using monoxime and antipyrine. The enzymatic reaction is carried out in a volume of 150 microliters and is stopped by the addition of 100 microliters of a color mix. After development, the absorbance at 460 nm is directly proportional to the quantity of N-carbamyl-L-aspartate up to at least 0.125 mumol and to the quantity of Escherichia coli aspartate transcarbamylase up to about 7 ng. Kinetic parameters obtained from saturation curves for L-aspartate in 50 mM Tris-acetate, pH 8.0, are indistinguishable from those previously obtained: Vmax = 26,225 mumol h-1 mg-1; S0.5 = 14.7 mmol liter 1; hill constant = 2.5. PMID- 2194398 TI - Kinetics of protease hydrolysis of extended peptide substrates: measurement by flow-injection analysis. AB - A flow-injection analysis (FIA) system was developed to study the enzyme catalyzed hydrolysis of synthetic peptides, each of which contained one scissile bond. The concentrations of alpha-amino groups in reactions mixtures were determined by FIA with o-phthalaldehyde as a fluorescence reagent. The method allows a rapid, precise, and sensitive determination of kinetic constants for proteases acting on extended peptide substrates. PMID- 2194399 TI - Lucigenin chemiluminescence as a probe for measuring reactive oxygen species production in Escherichia coli. AB - Addition of oxygen to whole cells of Escherichia coli suspended in the presence of the chemiluminescent probe bis-N-methylacridinium nitrate (lucigenin) resulted in a light emission increase of 200% of control. Addition of air to cells showed a chemiluminescent response far less than the response to oxygen. The redox cycling agents paraquat and menadione, which are known to increase intracellular production of O2- and H2O2, were also found to cause a measurable increase in lucigenin chemiluminescence in E. coli cells when added at concentrations of 1 and 0.1 mM, respectively. The oxygen-induced chemiluminescent response was not suppressed by extracellularly added superoxide dismutase or catalase. Further, the lucigenin-dependent chemiluminescent response of aerobically grown E. coli to oxygen was significantly greater than that of cells grown anaerobically. Heat killed cells showed no increase in chemiluminescence on the addition of either oxygen, paraquat, or menadione. These results show that lucigenin may be used as a chemiluminescent probe to demonstrate continuous intracellular production of reactive oxygen metabolites in E. coli. PMID- 2194400 TI - A fluorometric assay for HIV-protease activity using high-performance liquid chromatography. AB - A rapid sensitive method for the quantification of in vitro HIV-protease activity has been developed on the basis of the endoproteolytic conversion of N-Dns-SQ NYPIV to N-Dns-SQNY. The use of the N-dansyl group as a fluorescence label was shown to not significantly alter the apparent kinetic parameters for the peptide enzyme interaction. Using fluorescence detection, the dansylated product and unconverted substrate are detected in a single rapid (3 min) isocratic reverse phase HPLC separation in quantities as low as 0.2 pmol. The method is highly reproducible and suited to a variety of applications including the analysis of large sample numbers and rigorous enzymological studies. PMID- 2194401 TI - Application of a subtraction hybridization technique involving photoactivatable biotin and organic extraction to solution hybridization analysis of genomic DNA. AB - We have adapted a subtraction hybridization technique involving photoactivatable biotin, streptavidin binding, and organic extraction for solution hybridization analysis of mammalian genomic DNA. By combining maximal hybridization conditions of high salt, dextran sulfate, and formamide with successive hybridization steps and sequence enrichment by agarose gel electrophoresis, up to 97% of tracer DNA can be reproducibly driven to hybridize with photobiotinylated driver DNA. We demonstrate that the fractionation of hybridized from unhybridized sequences by this technique differs from hydroxyapatite chromatography with respect to the handling of nondenatured tracer, foldback sequences, and tracer-tracer hybrids. Strategies are presented to control the contribution of these species to the final subtracted product thereby making this technology a useful adjunct to solution hybridization approaches such as deletion cloning. PMID- 2194402 TI - New developments in biochemical mass spectrometry: electrospray ionization. AB - The principles, development, and recent application of electrospray ionization mass spectrometry (ESI-MS) to biological compounds are reviewed. ESI-MS methods now allow determination of accurate molecular weights for proteins extending to over 50,000, and in some cases well over 100,000. Similar capabilities are being developed for oligonucleotides. The instrumentation used for ESI-MS is briefly described and it is shown that, although ionization efficiency appears to be uniformly high, detector sensitivity may be directly correlated with molecular weight. The use of tandem mass spectrometry (e.g., MS/MS) for extending collision induced dissociation (CID) methods to the structural studies of large molecules is described. For example, effective CID of various albumin species (molecular weight approximately 66,000) can be obtained, far larger than obtainable for singly charged molecular ions. The combination of capillary electrophoresis, in both free solution zone electrophoresis and isotachophoresis formats, as well as microcolumn liquid chromatography with ESI-MS, provides the capability for on line separation and analysis of subpicomole quantities of proteins. These and other new developments related to ESI-MS are illustrated by a range of examples. Fundamental considerations suggest even more impressive developments may be anticipated related to detection sensitivity and methods for obtaining structural information. PMID- 2194403 TI - Blood transfusion, anesthesia, and host defense. PMID- 2194404 TI - Intestinal hemodynamics during laparotomy: effects of thoracic epidural anesthesia and dopamine in humans. AB - The effects of thoracic epidural anesthesia (TEA) and dopamine infusion (4 micrograms.kg-1.min-1) on superior mesenteric artery blood flow (SMABF), the mesenteric arteriovenous oxygen difference (AVDO2), and the mesenteric venous lactate concentration were studied in nine patients before abdominal aortic reconstruction. Thoracic epidural anesthesia reduced SMABF, as measured by electromagnetic flowmetry, to 77% +/- 8% (mean +/- SEM) of control (P less than 0.05), and mean arterial pressure to 46% +/- 4% of control (P less than 0.01). The mesenteric AVDO2 increased from 27 +/- 3 to 39 +/- 6 mL/L (P less than 0.05) and superior mesenteric venous lactate from 1.03 +/- 0.11 to 1.60 +/- 0.38 mmol/kg (P less than 0.05); systemic AVDO2 and lactate did not change. Dopamine had no significant effect on SMABF and mean arterial pressure before TEA. However, dopamine increased SMABF during TEA (from 77% +/- 8% to 137% +/- 21% of control; P less than 0.01), returned mesenteric AVDO2 to 27 +/- 3 mL/L (P less than 0.05), and elevated mean arterial pressure to 62% +/- 4% of control (P less than 0.05). It is concluded that the decrease in perfusion pressure during TEA reduces SMABF with resultant evidence of intestinal reductive metabolism. The intestinal blood flow during TEA was improved by dopamine. PMID- 2194405 TI - Operative lung continuous positive airway pressure to minimize FIO2 during one lung ventilation. PMID- 2194406 TI - Invasive Haemophilus influenzae type B infections: a continuing challenge. AB - Invasive Haemophilus influenzae type b infections are a major cause of severe infections in children between 2 months and 5 years of age. Meningitis, arthritis, pneumonia, cellulitis, osteomyelitis, and epiglottitis affect approximately 25,000 patients annually and are a major cause of mortality and morbidity in children. H. influenzae type b clinical syndromes, diagnostic methods, epidemiology, immunity, and treatment are discussed in this review. Although potent antibiotics have long been available for treatment, mortality and morbidity rates have not declined substantially in the last 15 years. Prevention of disease is therefore a continuous medical challenge. Secondary cases can be prevented by identification of the high-risk groups and the application of appropriate techniques, including antimicrobial prophylaxis. Primary prevention is the major goal of current research. H. influenzae type b vaccines currently are available for protection of infants 18 months of age and older. Prevention of primary and secondary disease and future developments, including new vaccine strategies, are stressed. PMID- 2194407 TI - Nosocomial infections in the pediatric patient: an update. AB - Substantial progress has been made in measuring the burden of nosocomial infection in pediatric patients, particularly in certain populations (e.g., critical care, immunocompromised, chronic care, and patients with acquired immunodeficiency syndrome) and after certain procedures (e.g., central catheter lines and open-sternum cardiovascular surgery). Preventive measures, such as the use of goggles, gowns, and gloves, have been subjected to new and additional study. The following report is a summary of recent progress. A review of factors responsible for infection in various patient care populations and settings and recommendations for control are presented. PMID- 2194408 TI - [Energy metabolism and craniocerebral injury]. AB - Severe head injury induces major hormonal, humoral and metabolic changes, characterized by increases in stress hormone secretion, lymphokines production, associated with high lipid and protein catabolism as well as changes in energy expenditure (EE). Numerous factors influence EE in head-injured patients, particularly anthropometric data, body temperature, nutritional support, level of consciousness, muscular tone and activity. Resting EE is usually increased following brain trauma; however, normal or decreased metabolic rates can be observed in curarized patients on mechanical ventilation or in patients receiving high doses of barbiturates. PMID- 2194409 TI - [Cerebral infarction in pernicious malaria. Diagnostic value of computed tomography]. AB - Case report of a severe form of neuropaludism, contracted in a territory with Plasmodium falciparum completely insensitive to chloroquine. CAT Scan views displayed a small brain infarction. Complete recovery was obtained with a treatment including quinine, tracheal intubation and ventilatory support, sedation with barbiturates. CAT Scan views demonstrated a complete regression of cerebral lesions. PMID- 2194410 TI - Primary malignant melanoma of the adrenal gland. A report of two cases and review of the literature. AB - Primary malignant melanoma of the adrenal gland is an established entity despite early doubts. It originates in the adrenal medulla from cells derivative of the neural crest. Because of the high frequency of metastatic involvement of the adrenal by cutaneous and ocular melanomas, rigid diagnostic criteria should be followed. Only four cases of this lesion have been reported since 1946. Review of these four together with the two described in this article shows that primary adrenal melanoma is a highly malignant tumor of middle age that often manifests as a painful flank mass. Distant lymph node metastases can be seen as a presenting sign. Treatment is not effective with a mortality rate approaching 100 per cent within two years. Since the true melanocytic origin of primary adrenal melanoma has not been established and because of the similarity of its pathologic findings with the pheochromocytomas, we believe that adrenal melanoma arises from the pheochromocytes and should be called "melanotic malignant pheochromocytoma." PMID- 2194411 TI - Revascularization of a symptomatic pseudoaneurysm of the anterior tibial artery. AB - Traumatic pseudoaneurysms of the peripheral arterial vasculature occur infrequently. The majority of the experience with these lesions is from this century's wartime experience. Pseudoaneurysms of the tibial vessels comprise only three to seven per cent of all pseudoaneurysms and only seven cases of anterior tibial artery pseudoaneurysms have been reported in the American and British literature since World War II. A high index of suspicion must be maintained for prompt detection of these lesions. Formerly, injuries of the tibial vessels were managed by nonoperative measures or exploration and arterial ligation. These approaches were met with varying results. The evolution of current vascular surgical techniques allows successful reconstruction of these vessels. We wish to report a successful method of repair of symptomatic pseudoaneurysm of the anterior tibial artery using a saphenous vein interposition graft. This technique restored arterial continuity and allowed maximal opportunity for limb salvage. Additional management techniques are discussed and compared in order to improve rapid diagnosis and provide efficient treatment. PMID- 2194412 TI - Local resection of tumors of the ampulla of Vater. AB - Local resection of an ampullary tumor with reimplantation of the pancreatic and bile ducts was first described by William S. Halsted in 1899. Technical hazard and unsuitability in malignant ampullary tumors have unfortunately led to a disregard for this operation that is unwarranted. Radical pancreaticoduodenectomy is now the most common method of resecting benign and malignant ampullary tumors. Experience was gained with two high-risk patients with benign adenomatous polyps obstructing the ampulla of Vater. Their medical unsuitability for radical pancreaticoduodenectomy led us to revive the procedure of wide local excision of these tumors with reimplantation of the pancreatic and bile ducts. Operative time and blood loss were substantially less than radical resection and postoperative recoveries were relatively uncomplicated. Radical resection of benign ampullary tumors may be appropriate for good-risk patients in whom the risk of local recurrence outweighs the operative risk. We suggest that local resection of benign ampullary tumors is the procedure of choice in high-risk patients and that it be considered in palliation of limited local malignancies of the ampulla in high-risk patients. PMID- 2194413 TI - Surgical approach to atrial septal defect in the female. Right thoracotomy versus sternotomy. AB - Repair of atrial septal defect (ASD) remains a high-benefit, low-risk procedure due to technologic improvements. From July 1981 to December 1986, 35 females (age, 7 months to 28 years) had repair of ASD; 20 by right thoracotomy and aortic cannulation (group 1) and fifteen by median sternotomy (group 2). In general, right thoracotomy was applied to patients with secundum ASD two years or older and without associated lesions, while median sternotomy was applied to patients with ostium primum lesions and/or associated lesions. Patients or their families perceived the cosmetic results superior to the right thoracotomy approach over the median sternotomy. We feel that a right thoracotomy and aortic cannulation is effective in females (2 years and older) with secundum ASD for a superior cosmetic result over median sternotomy. However, females with ostium primum and/or associated lesions should undergo median sternotomy for better cardiac access and safety. PMID- 2194414 TI - Percutaneous cholecystostomy and lithotripsy of gallstones. AB - Extracorporeal lithotripsy has a high incidence of postprocedure biliary colic and slow disappearance of gallstones. This situation has led to the development of a new technique which has been successful in four patients and consists of percutaneous cholecystostomy, direct stone visualization, and fragmentation of gallstones with a percutaneous lithotripter. All patients had a functioning gallbladder, stone diameter less than 30 mm, and abdominal pain secondary to cholelithiasis. The procedure was performed in a two day hospitalization. Initially, under general anesthesia, the gallbladder was intubated with a 21 gauge needle and guidewire and the tract dilated to #30 French. A nephroscope was advanced into the gallbladder through a rigid sheath. All gallstones were visualized, fragmented with a percutaneous lithotripter, and extracted. After a postoperative cholecystocholangiogram, an self-retaining catheter was placed in the gallbladder for an average of 2.5 days. Three of the four patients were discharged from the hospital in two days without any complications. A fourth patient had a small bile leak treated with antibiotics. After an average of 13 months follow-up, all patients had a normal ultrasound or oral cholecystogram and no biliary tract symptoms. This technique is safe and efficient in removing gallstones and has no recurrence of gallstones in the 13 month follow-up period. PMID- 2194415 TI - Endoscopic retrograde cholangioscopy. An adjunct to endoscopic exploration of the common bile duct. AB - Choledochoscopy is an accepted technique in the operative exploration of the common bile duct, and is complimentary to operative cholangiography. Retrograde cholangiography can be achieved perorally in up to 97 per cent of patients and it is reasonable to assume that the use of complimentary cholangioscopy in such patients would help to improve the accuracy of bile duct examination just as it does when applied in the operative setting. We have had the opportunity to use a new technology in the endoscopic evaluation of the common bile duct. An endoscopic retrograde cholangioscopy (ERCP) is first performed and ductal anatomy outlined. When indicated, an endoscopic sphincterotomy is performed. If large stones are present they are removed with a balloon or basket. The standard side viewing endoscope is then removed and replaced with the large channel, side viewing scope. A "baby" scope is introduced through the "mother" scope and canulation of the common duct with the "baby" scope is performed. Biopsies and brushings of lesions may be obtained and numerous instruments are available for manipulation through the biopsy channel of the "baby" scope. The use of retrograde cholangioscopy as an adjunct to retrograde cholangiography should provide the same advantages that have been demonstrated with the use of operative choledochoscopy. Use of this instrument will allow the endoscopist to accurately identify questionable lesions seen on the cholangiogram, selectively canulate particular biliary radicals, biopsy lesions of the common duct, and perhaps intervene therapeutically in selected biliary tract lesions. PMID- 2194416 TI - Management of general surgical emergencies in pregnancy. AB - The management of 25 pregnant patients (gestational age 4-40 weeks) treated at Henry Ford Hospital from 1980-86 was reviewed. Eleven women were treated for a variety of nontraumatic general surgical emergencies including cholecystitis, appendicitis, pancreatitis, and gastrointestinal obstruction. Fourteen women were treated after sustaining traumatic injuries. Ten patients were managed without operation and 15 required surgical intervention as part of their treatment. Diagnostic studies that proved helpful included diagnostic peritoneal lavage, ultrasonography, intravenous pyelography, and roentgenograms of the chest and abdomen. There were no maternal deaths, but two fetal deaths occurred as a result of traumatic injuries. Five women and one neonate developed major complications requiring prolonged hospitalization. Early aggressive resuscitation and thorough diagnostic evaluation are required to achieve a favorable outcome in the management of the pregnant patient who presents with an emergent general surgical problem. PMID- 2194418 TI - Mirizzi's syndrome. An uncommon cause of biliary obstruction. AB - An uncommon cystic-duct anomaly characterized by a course parallel to the common hepatic duct or contained in a sheath with the common hepatic duct over a significant distance can allow cystic-duct stones to occlude the common hepatic duct by extrinsic pressure. This condition is appropriately referred to as Mirizzi's syndrome. One such case is described in the present study. Recognition of this and other biliary anomalies is critical to safe operative management of calculous biliary disease. PMID- 2194417 TI - Antibiotics in elective colon surgery. A randomized trial of oral, systemic, and oral/systemic antibiotics for prophylaxis. AB - A prospective, randomized double-blind study was undertaken to compare the efficacy of three prophylactic regimens (oral neomycin and erythromycin, intravenous cefoxitin, and a combination of both oral and intravenous antibiotics) in patients undergoing elective colorectal surgery. One hundred sixty-nine patients were randomized and 146 patients were evaluable. Septic complications occurred in 11.4 per cent of patients receiving oral antibiotics only, in 11.7 per cent of patients receiving intravenous cefoxitin alone, and in 7.8 per cent of patients receiving both oral and intravenous antibiotics. These differences were not statistically different. The greatest number of septic complications occurred in those patients with anastomotic disruptions. Two patients died (1.3%), both of whom had major anastomotic failures. There was no advantage between any of the groups in the incidence of wound infection (3.9 6.8%). Thus, no advantage could be identified in this study in the combination of oral and intravenous antibiotics in elective colorectal surgery. PMID- 2194420 TI - Electrophysiology in Guillain-Barre syndrome. AB - Clinical electrophysiological studies are important in the evaluation of patients with Guillain-Barre syndrome. Physiological evidence of demyelination occurs in almost all patients with Guillain-Barre syndrome, especially if serial studies are performed. Criteria for demyelination are proposed. Prognostic information concerning patient outcome can be deduced from computation of the mean of the summed motor evoked compound muscle action potential amplitudes from distal stimulation. Future studies of the electrophysiology of Guillain-Barre syndrome should allow increased use of the data for prognostication and should enhance our understanding of the mechanisms of the disease. PMID- 2194419 TI - Guillain-Barre syndrome: clinical and therapeutic observations. AB - Better outcomes for patients with Guillain-Barre syndrome are associated with five factors: younger age, no requirement for respiratory assistance, slower progression of disease, normal peripheral nerve function by electrodiagnostic criteria, and treatment by plasmapheresis. Plasmapheresis is the only factor that the treating physician can modify. Consideration of the use of plasmapheresis in children, type of replacement fluid, plasma exchange by simpler methods than plasmapheresis, and possible alternative approaches to therapy are discussed. PMID- 2194421 TI - Guillain-Barre syndrome: historical aspects. AB - Historical aspects of the Guillain-Barre syndrome are traced from its first clear description in 1916. Emphasis is placed on the swine flu incident of 1976 and 1977. Although Guillain-Barre syndrome is a descriptive clinical entity with relatively widely accepted diagnostic criteria, it lacks nosological delimitation. The topography, pathological features, pathophysiology, and prognostic features are well understood, but the immunopathogenesis of the disease remains uncertain. PMID- 2194422 TI - Assessment of current diagnostic criteria for Guillain-Barre syndrome. AB - Criteria for the diagnosis of Guillain-Barre syndrome are reaffirmed. Electrodiagnostic criteria are expanded and specific detail added. PMID- 2194423 TI - Immunological parameters in Guillain-Barre syndrome. PMID- 2194424 TI - Antibody detection in Guillain-Barre syndrome. AB - Chromatograms with appropriate separated ganglioside fractions were overlaid with diluted patient sera, and antibody binding was detected with an alkaline phosphatase-labelled second antibody. Antiganglioside antibodies were present in the sera of 39 of 50 patients with Guillain-Barre syndrome (GBS), in 10 of 12 patients with Alzheimer's disease, and in approximately 30% of the controls. The antibodies were directed against ganglioside 3'-LM1, shown to be the major ganglioside of peripheral nerve (femoral nerve and cauda equina) in most of the positive GBS sera but also in a high proportion in the controls. No correlation was found between the severity or the course of the disease and the antibody titer. Daily parenteral administration of purified bovine brain-derived GM1 ganglioside for three months to 12 patients with Alzheimer's disease did not result in any antiganglioside GM1 antibodies. We have interpreted our findings in the following way. Human sera normally contain naturally occurring antibodies against gangliosides that in general do not cause any tissue damage. Thus, parenteral injection of gangliosides will not lead to any antibody formation. PMID- 2194425 TI - Neuropathy and anti-GM1 antibodies. AB - Increased titers of IgM antibodies that react with carbohydrate epitopes on GM1 are present in some patients with lower motor neuron disease, sensorimotor neuropathy, or motor neuropathy with or without conduction block. Therapeutic reduction of antibody concentrations can result in clinical improvement, suggesting that the antibodies may be pathogenic. The anti-GM1 antibodies react with carbohydrate epitopes, which are shared by several other glycolipids and glycoproteins in the central and peripheral nervous system. The antibodies might exert their effects at a number of sites, depending on the topographical distribution of the target antigens and on their accessibility. B-cells that express anti-GM1 antibodies are present at birth and are normally suppressed or rendered anergic. Under some circumstances, however, they might be activated to secrete autoantibodies that cause autoimmune neuropathy. PMID- 2194426 TI - Characterization of complement-fixing antibodies to peripheral nerve myelin in Guillain-Barre syndrome. AB - Complement-fixing antibodies to peripheral nerve myelin (anti-PNM Ab) can be detected in the serum of patients with Guillain-Barre syndrome (GBS). Kinetics of these antibodies can be correlated with the changing clinical course; the appearance of activation products of the terminal complement cascade in cerebrospinal fluid, serum, and peripheral nerve of patients with GBS; and the ability of GBS serum to mediate complement-dependent demyelination of myelinating cultures of rodent dorsal root ganglion. Some of the anti-PNM Ab in all GBS serum tested thus far bind a neutral glycolipid of human PNM and cross react with Forssman antigen, a cross-species antigen found in many infectious agents. Studies suggest that an IgM antibody in GBS patients that could be triggered by multiple infectious agents binds a surface determinant of a Forssman-like lipid of human PNM and participates in demyelination of peripheral nerve through the activation of complement. PMID- 2194427 TI - Antibodies to gangliosides and myelin proteins in Guillain-Barre syndrome. AB - An earlier investigation from our laboratory (Ilyas AA, Wilson HJ, Quarles RH, et al. Serum antibodies to gangliosides in Guillain-Barre syndrome. Ann Neurol 1988;23:440-447) demonstrating the presence of high levels of antiganglioside ganglioside antibodies in the sera of 5 of 26 patients with Guillain-Barre Syndrome (GBS) but not in control sera is summarized. The ganglioside antigens varied among the 5 patients with positive findings, and the antiganglioside antibodies decreased concurrently with clinical improvement in those patients for whom longitudinal samples were available for analysis. The results are discussed in the context of antibodies to acidic glycolipids in other types of neuropathy and other studies on antiglycolipid antibodies in GBS. Data showing the occurrence of lower levels of antibodies to P2 protein, P0 glycoprotein, and myelin-associated glycoprotein in some of the GBS patients are also summarized. The findings from our laboratory combined with the results of others make it unlikely that antiganglioside antibodies have a notable pathogenic effect in most patients with GBS, but the possibility remains that they are of pathogenic importance in some patients with the highest antibody titers. PMID- 2194428 TI - Measurement and clinical importance of antibodies to glycosphingolipids. AB - Measurement of antibodies against gangliosides and other glycosphingolipids (GSLs) is technically demanding because of their low affinity for antigen. A recent workshop, in which twelve laboratories received a coded panel of sera containing anti-GM1 antibodies, demonstrated that the immunoassays varied widely in sensitivity and in criteria employed for a positive test. The fine specificity of anti-GSL antibodies should be characterized by analyzing their reactivity with a panel of GSLs with related structures. High-titer monoclonal IgM antibodies against gangliosides and sulfated carbohydrates appear to cause neuropathy in some patients. Low-titer polyclonal antibodies against gangliosides occur frequently in a variety of diseases, including autoimmune diseases without neurological symptoms. It is unclear whether these polyclonal antibodies are a primary manifestation or a consequence of the disease, and their clinical importance is uncertain at present. PMID- 2194429 TI - T-cell and macrophage activation in experimental autoimmune neuritis and Guillain Barre syndrome. AB - Evidence implicating cellular immune responses in the pathogenesis of experimental autoimmune neuritis (EAN) and Guillain-Barre syndrome (GBS) is reviewed. In EAN the decisive role of T-lymphocytes in the initiation of immune mediated nerve damage has been firmly established by adoptive transfer experiments. Macrophages but not Schwann cells express major histocompatibility complex class II gene products in situ and hence may function as antigen presenters. Macrophages are crucial in the amplification and effector phase and damage the myelin sheath by phagocytic attack and release of inflammatory mediators such as toxic oxygen radicals, arachidonic acid metabolites, complement, or hydrolases. Macrophage activation in EAN is achieved by interferon gamma. Attempts to detect specific sensitization of T-lymphocytes to nerve antigens in patients with GBS have so far been unsuccessful. However, circulating activated T cells can be found in patients with GBS, as evidenced by augmented expression of HLA-DR antigen, the transferrin receptor, and the interleukin-2 receptor on the surface of peripheral blood T cells, and by increased serum concentrations of interleukin-2 and the soluble interleukin-2 receptor. In addition, we present data indicating macrophage activation in GBS. PMID- 2194430 TI - Macrophage responses in inflammatory demyelinating neuropathies. AB - Macrophages are prominent participants in inflammatory demyelinating neuropathies. To provide a different means of evaluating macrophage behavior, we used immunostaining of teased nerve fibers and endoneurial blood vessels. We assessed the frequency with which macrophages were seen in inflammatory demyelinating neuropathies, their relationship to normal and demyelinating fibers, and their expression of major histocompatibility Class II markers (Ia antigen). In 6 patients with chronic inflammatory neuropathy and 1 with Guillain Barre syndrome, we found regularly that macrophages were adherent to teased blood vessels. Cells presumed to be entering the nerve were elongated, often with a polarized appearance suggesting motility, and were Ia-positive. After entry into nerve, the Ia-positive macrophages were adherent to both normal and demyelinating fibers. They often retained their Ia positivity after penetrating into the nerve fiber and removing myelin. Foamy macrophages, judged to be postphagocytic, were Ia-negative. The foamy macrophages found adhering to blood vessels were presumed to be leaving the nerve. This pattern of entry as Ia-positive prephagocytic cells and evolution to Ia-negative foamy macrophages was compared with other experimental and human neuropathies. PMID- 2194431 TI - The epidemiology of Guillain-Barre syndrome. AB - Population-based studies of Guillain-Barre syndrome (GBS) give crude average annual incidence rates varying from 0.4 to 1.7 per 100,000 population. The reported incidence is influenced by the diagnostic criteria adopted as well as the thoroughness of case-finding. Variations in these account for some of the lack of uniformity between different studies. Data from the Mayo Clinic based on National Institute of Neurological Disorders and Stroke diagnostic criteria and thorough ascertainment methods gave a crude incidence of 1.7 per 100,000 per year (x 10(-5]. Incidence was higher in females (2.3 x 10(-5] than males (1.2 x 10(-5] as well as in older compared to younger people (3.2 x 10(-5) over age 60 and 0.8 x 10(-5) under age 18, respectively). The disease reached a nadir after onset at 8 days on average, and the illness lasted an average of 12 weeks. Most patients (75%) recovered completely. Recent epidemiological studies of GBS suggest no clear secular trend. Incidence does fluctuate with time but not clearly with season. In virtually all studies "triggering" factors are implicated, but they appear to be diverse, making it less likely, from an epidemiological perspective, that a single antigen is of etiological importance in GBS. PMID- 2194432 TI - Mechanisms of autoimmune neuropathies. AB - Our studies have focused on the mechanisms involved in blood-brain barrier and blood-nerve barrier alterations in inflammatory demyelinating diseases. The results support the conclusion that these diseases are initiated by delayed hypersensitivity reactions. They further demonstrate a role for mast cell degranulation and vasoactive amines in the peripheral nerve. In the central nervous system, our studies have documented both active and passive mechanisms of edema formation and support the conclusion that cytokines may be involved in altered blood-brain barrier permeability and inflammation. We conclude that several mechanisms of barrier breakdown are activated in the inflammatory demyelinating diseases and that alteration in endothelial cell function is a major component of disease induction. PMID- 2194433 TI - [Is it necessary to combine the surgical treatment of kidney adenocarcinoma with ipsilateral adrenalectomy?]. AB - We analyzed a series of 202 renal adenocarcinomas, 164 of which were submitted to radical nephrectomy. Pathological analyses of 150 adrenal glands revealed ipsilateral adrenal metastasis in 4 cases, 3 of these coexisting with other distant metastases. The primary tumors in these 4 cases were highly undifferentiated and in the advanced local tumor stage; the only case with solitary adrenal metastasis survived 15 months. The present study and data reported in the literature indicate that ipsilateral adrenalectomy should be performed in addition to radical nephrectomy only in renal tumors of the upper pole, those localized at other sites but whose size indicate the possibility of tumor spreading to the adjacent adrenal gland, or when a suspicious mass in the adrenal gland is evidenced by the preliminary workup or during surgery. PMID- 2194434 TI - [Valves of the anterior urethra]. AB - Despite the cases reported in the literature, anterior urethral valves continue to be an uncommon condition. The foregoing has to be considered when evaluating children with urinary obstruction or recurrent infections. A case of anterior urethral valves associated with segmental saccular dilatation of the urethra is described and the diagnostic methods are highlighted. PMID- 2194435 TI - [Lymphoma of the penis]. AB - A case of lymphoma of the penis in a 67-year-old patient is described herein. The literature is reviewed, highlighting its rarity, different forms of presentation, and the therapeutic modalities--which have yet to be well-defined--utilized in some of the cases. We underscore the importance of currently available diagnostic tools in determining the nature of this penile tumor. PMID- 2194436 TI - [Hemangioma of the testis: a problem of clinical diagnosis]. AB - Vascular tumors of the testis are uncommon. A review of the literature showed that only 10 such cases have been reported. Another case of cavernous hemangioma of the testicle is described. Its clinical features, different histological patterns, treatment and its biological significance are discussed. PMID- 2194438 TI - ["Entrapped" popliteal artery: pathology and pathogenesis. Report of 7 cases with review of the literature]. AB - In this study, the author reports on the pathological aspect in seven cases of "entrapped" popliteal artery. Alterations observed were similar to arteriosclerotic changes. The pathologic aspect is not specific. The physiopathogenic mechanism of this arteriopathy is similar to that of the chronic vascular compression syndrome due to pre-existing anatomic abnormalities, such as the thoraco-brachial outlet syndrome of the subclavian artery. Chronic compression of the popliteal artery is considered as a localized microtrauma of the arterial wall. PMID- 2194437 TI - [Extra-skeletal Ewing's sarcoma. A case report with detailed review of the literature]. AB - Extra-skeletal Ewing's Sarcoma (EES): a clinico-pathological entity described in 1975 by L. Angervall and F.M. Enzinger. This article reports a new case in which the primary was localized in the right forearm and metastasized to the left lung fourteen years later. A detailed review of the literature emphasized similarities and differences between osseous and extra-osseous Ewing's Sarcoma. PMID- 2194439 TI - Acute pancreatitis at its centenary. The contribution of Reginald Fitz. AB - 1989 represents the 100th anniversary of Reginald Fitz's initial characterization of acute pancreatitis. Our current understanding of this disease has advanced little beyond Fitz's early description. While survival from pancreatitis has improved largely through advancements in critical care techniques, no medical or surgical therapy exists that can limit pancreatic autodigestion and inflammation. Recent investigations have suggested that pancreatitis may result from a disruption of normal stimulus-secretion coupling within the acinar cell. Future research based on these observations may ultimately result in successful therapy for this disease. PMID- 2194441 TI - [Television, the child and the pediatrician]. PMID- 2194440 TI - Molecules, cancer, and the surgeon. A review of molecular biology and its implications for surgical oncology. AB - Interactions between molecules control intra- and intercellular physiology. Cancer is emerging as a disease in which individual molecules are either overproduced, mutated, expressed at inappropriate stages of development, or lost due to inheritance or aberrant mitotic division. The major players in this contest of cellular control are growth factors, growth factor receptors (GFRs), signal transducers, and dominant or suppressor/recessive oncogenes. The tumors most frequently removed by surgeons have been reported to have changes in one or another of these types of molecules. The concept of multistage carcinogenesis, whereby malignancy arises after a sequence of changes that are cumulative, and passed from progenitor to daughter cells, is also being defined as a sequence of molecular, genetic, and chromosomal alterations. Molecular antineoplastic therapy is in early stages of development at the laboratory bench. The future may see patients screened for cancer susceptibility, evaluated for adjuvant therapy, and chosen for particular treatment based on molecular analysis. The types of cancer operations and the scope of surgical resection may change as molecular techniques enhance oncologic treatment. PMID- 2194442 TI - [Glucocorticoids in asthmatic crisis in children]. AB - Systemic corticosteroids are misused in children with acute asthma. Their misuse is one of the factors responsible for the recent increase in asthma mortality. Since 1980, 10 of 12 double blind randomized clinical trials have shown the beneficial effects of corticosteroids in acute asthma incompletely responsive to bronchodilatators. The value of early course-high dose-short term corticosteroid therapy is emphasized. The side effects of such short corticosteroid courses are minimal and transient. Management of asthma should be reconsidered if steroid courses are too frequent. PMID- 2194443 TI - Neuropathology of the acquired immunodeficiency syndrome. AB - This review attempts to assess critically the literature on the neuropathology of acquired immunodeficiency syndrome in light of our experience with 172 patients with acquired immunodeficiency syndrome who underwent extensive postmortem examinations of the central and peripheral nervous systems. The neuropathologic manifestations of the disease can be divided into three categories: (1) primary or putative/indirect effects of the human immunodeficiency virus, (2) opportunistic infections, and (3) neoplasms. We discuss the known etiologic agents and postulated pathogenetic mechanisms responsible for the broad range of neurologic diseases observed in patients with acquired immunodeficiency syndrome. PMID- 2194444 TI - Ultrastructural morphometry in the diagnosis of Sezary syndrome. AB - Blood specimens from 87 patients and control subjects were prepared for electron microscopy and subjected to ultrastructural morphometric evaluation by using a computerized planimeter. A statistical comparison of means indicated that patients with Sezary syndrome could be distinguished from normal subjects and patients with reactive lymphocytosis, by using mean nuclear perimeter and form factor values. The lymphocytic nuclei from patients with infectious mononucleosis were more lobated on visual inspection than those from normal subjects; the difference in mean form factor values was statistically significant. The simple histogram method was most discriminatory and distinguished patients with Sezary syndrome from patients with other types of lymphoid leukemias and reactive lymphocytosis, including infectious mononucleosis. The histogram method could not, however, distinguish patients with Sezary syndrome from patients with T-cell chronic lymphocytic leukemia and Japanese T-cell leukemia. The use of bivariate graphic displays (plotting nuclear size and shape measurements) placed the lymphoid cells of the various types of lymphoproliferative disorders into distinct morphometric domains. Computerized morphometric techniques may, therefore, be of greater value when the range of possible diagnoses is large. PMID- 2194446 TI - [Experience in teaching anatomy to foreign students]. PMID- 2194445 TI - Adenomatoid tumor of the adrenal gland with ultrastructural and immunohistochemical demonstration of a mesothelial origin. AB - We describe an adenomatoid tumor arising in the left adrenal gland of a patient who underwent bilateral adrenalectomy for the ectopic adrenocorticotropic hormone syndrome. The mesothelial origin of the tumor was confirmed by electron microscopy and positive immunohistochemical staining for keratin. The tumor had a prominent cystic component raising the question whether adrenal cysts are derived from mesothelial inclusions. It is proposed that consideration be given to adding a new category of "mesothelial cysts" to the classification of adrenal gland cysts. PMID- 2194447 TI - Expression of human glutathione S-transferases in Saccharomyces cerevisiae confers resistance to the anticancer drugs adriamycin and chlorambucil. AB - Adaptation and resistance to chemicals in the environment is a critical part of the evolutionary process. As a result, a wide variety of defence systems that protect cells against chemical insult have evolved. Such chemical resistance mechanisms appear to play a central role in determining the sensitivity of human tumours to treatment with chemotherapeutic drugs. The glutathione S-transferases (GST) are important detoxification enzymes whose over-expression has been associated with drug-resistance. In order to evaluate this possibility we have expressed the human Alpha-class and Pi-class GST cDNAs that encode GST B1B1 and GST pi in the yeast Saccharomyces cerevisiae. The expression of GST B1B1 or GST pi resulted in a marked reduction in the cytotoxic effects of chlorambucil, a bifunctional alkylating agent, and an anthracycline, adriamycin. These data provide direct evidence that the over-expression of GST in cells can confer resistance to anticancer drugs. PMID- 2194448 TI - The insulin A and B chains contain structural information for the formation of the native molecule. Studies with protein disulphide-isomerase. AB - It has been shown previously [Tang, Wang & Tsou (1988) Biochem. J. 255, 451-455] that, under appropriate conditions, native insulin can be obtained from scrambled insulin or the S-sulphonates of the chains with a yield of 25-30%, together with reaction products containing the separated A and B chains. The native hormone is by far the predominant product among the isomers containing both chains. It is now shown that the presence of added C peptide has no appreciable effect on the yield of native insulin. At higher temperatures the content of the native hormone decreases whereas those of the separated chains increase, and in no case was scrambled insulin containing both chains the predominant product in the absence of denaturants. Both the scrambling and the unscrambling reactions give similar h.p.l.c. profiles for the products. Under similar conditions cross-linked insulin with native disulphide linkages can be obtained from the scrambled molecule or from the S-sulphonate derivative with yields of 50% and 75% respectively at 4 degrees C, and with a dilute solution of the hexa-S-sulphonate yields better than 90% can be obtained. The regenerated product is shown to have the native disulphide bridges by treatment with CNBr to give insulin and by the identity of the h.p.l.c. profile of its peptic hydrolysate with that for cross-linked insulin. It appears that the insulin A and B chains contain sufficient information for the formation of the native molecule and that the role of the connecting C peptide is to bring and to keep the two chains together. PMID- 2194450 TI - Protein turnover is elevated in muscle of mdx mice in vivo. AB - mdx mice lack the protein dystrophin, the absence of which causes Duchenne muscular dystrophy in humans. To examine how mdx mice maintain muscle mass despite dystrophin deficiency, we measured protein turnover rates in muscles of mdx and wild-type (C57BL/10) mice in vivo. At all ages studied, rates of muscle protein synthesis and degradation were higher in mdx than in C57BL/10 mice. PMID- 2194451 TI - Protein folding/refolding analysis by mass spectrometry. Scrambling of disulphide bridges in insulin. AB - In this paper we present a protocol that allows a dynamic analysis of disulphide bridge formation, based on freezing the intermediates by acid/acetone precipitation, followed by digestion with pepsin and direct fast-atom-bombardment mass-spectrometric analysis. A rapid definition of the exact nature of disulphide bridges formed can be obtained via a definitive assignment of disulphide-linked peptides according to their unique mass values. With the use of an appropriate thiol concentration, scrambling of the native disulphide bonds in bovine insulin occurs, and the process is catalysed by protein disulphide-isomerase (EC 5.3.4.1). The disruption of native and the formation of new disulphide bonds can be monitored as described above, and interestingly B-chain dimers containing Cys B7-Cys-B7 and Cys-B7-Cys-B19 bonds are detected. PMID- 2194449 TI - Protein kinase C activators selectively inhibit insulin-stimulated system A transport activity in skeletal muscle at a post-receptor level. AB - We have investigated the role of phorbol esters on different biological effects induced by insulin in muscle, such as activation of system A transport activity, glucose utilization and insulin receptor function. System A transport activity was measured by monitoring the uptake of the system A-specific analogue alpha (methyl)aminoisobutyric acid (MeAIB), by intact rat extensor digitorum longus muscle. The addition of 12-O-tetradecanoylphorbol 13-acetate (TPA, 0.5 microM) for 60 or 180 min did not modify basal MeAIB uptake by muscle, suggesting that insulin signalling required to stimulate MeAIB transport does not involve protein kinase C activation. However, TPA added 30 min before insulin (100 nM) markedly inhibited insulin-stimulated MeAIB uptake. The addition of polymyxin B (0.1 mM) or H-7 (1 mM), protein kinase C inhibitors, alone or in combination with TPA leads to impairment of insulin-stimulated MeAIB uptake. This paradoxical pattern is incompatible with a unique action of Polymyxin B or H-7 on protein kinase C activity. Therefore these agents are not suitable tools with which to investigate whether a certain insulin effect is mediated by protein kinase C. TPA did not cause a generalized inhibition of insulin action. Thus both TPA and insulin increased 3-O-methylglucose uptake by muscle, and their effects were not additive. Furthermore, TPA did not modify insulin-stimulated lactate production by muscle. In keeping with this selective modification of insulin action, treatment of muscles with TPA did not modify insulin receptor binding or kinase activities. In conclusion, phorbol esters do not mimic insulin action on system A transport activity; however, they markedly inhibit insulin-stimulated amino acid transport, with no modification of insulin receptor function in rat skeletal muscle. It is suggested that protein kinase C activation causes a selective post receptor modification on the biochemical pathway by which insulin activates system A amino acid transport in muscle. PMID- 2194452 TI - Synthesis and properties of vinyl carbamate epoxide, a possible ultimate electrophilic and carcinogenic metabolite of vinyl carbamate and ethyl carbamate. AB - Vinyl carbamate reacted with dimethyldioxirane in dry acetone to give a high yield of pure crystalline vinyl carbamate epoxide. This epoxide was characterized by its NMR and MS spectra and elementary analysis. It is unstable at room temperature and has a half-life in water solution of approximately 32 minutes. It reacts with adenosine to form 1,N6-ethenoadenosine and more of this etheno nucleoside was found in hydrolysates of hepatic RNA of male mice injected i.p. with the epoxide than with vinyl carbamate. Tests with Salmonella typhimurium TA1535 showed that this epoxide is a strong direct mutagen. It is also more toxic in the mouse than vinyl carbamate. Studies on the carcinogenicity of this epoxide are in progress. PMID- 2194453 TI - A nitrogen-fixation gene (nifC) in Clostridium pasteurianum with sequence similarity to chlJ of Escherichia coli. AB - The molybdenum-containing nitrogenase contains an iron-molybdenum cofactor, whose synthesis involves at least six nif genes. Genes corresponding to nifE, N, B, and V occur in proximity in Clostridium pasteurianum, with nifN-B occurring as one gene and with nifV omega and nifV alpha in place of nifV. Between nifN-B and nifV omega V alpha, we found a gene whose sequence is similar to chlJ of Escherichia coli. chlJ is part of the chlD locus, which is involved in Mo transport. C. pasteurianum actively accumulates Mo in a process coregulated with nitrogen fixation. We propose that nifC is involved in Mo transport. The expression of nifC may be coregulated with nitrogen fixation because of the presence of nif distinctive promoter and upstream sequences preceding nifC-nifV omega-nifV alpha. NifC contains a region typical of integral membrane proteins. Our findings suggest the involvement of a membrane-located nif gene product in Mo transport in C. pasteurianum. PMID- 2194454 TI - Expression of simian virus 40 large T antigen in Escherichia coli using vectors based on the regulatable rac promoter. AB - Simian Virus 40 large T antigen is a multi-functional protein that is involved in the initiation of viral DNA replication, regulation of viral transcription and cell transformation. Bacterial expression vectors, pER23-1 and pER23-2, that are based on the regulatable rac promoter were used to produce T antigen either as a free protein or as a fusion protein. We have observed efficient transcription of the cloned T antigen gene in most of the recombinants. However, expression of the T antigen protein was inefficient and most of the expressed protein was truncated. This may be due to differences in codon usage in E. coli or to rapid protein degradation. PMID- 2194455 TI - Characterization of endothelin converting enzyme activities in soluble fraction of bovine cultured endothelial cells. AB - Endothelin converting enzyme activities in the soluble fraction of cultured bovine aortic endothelial cells were characterized. The two major endothelin converting enzyme activities were eluted from a hydrophobic chromatography column and the elution profile of the endothelin converting enzyme activities was the same as that of cathepsin D activities. These activities had a same pH optimum at pH 3.5 and were effectively inhibited by pepstatin A. Furthermore, anti-cathepsin D antiserum absorbed these activities as well as cathepsin D activity. Immunoblotting analysis using the antiserum showed the major active fractions have immunostainable components of identical molecular weights with cathepsin D. From these results, we concluded that the major endothelin converting activities in the soluble fraction of endothelial cells are due to cathepsin D. In addition to these cathepsin D activities, a minor endothelin converting enzyme activity with an optimum pH at 3.5 was found, which does not have angiotensin I generating (cathepsin D) activity from renin substrate and needs much higher concentrations of pepstatin A to inhibit the activity than cathepsin D. PMID- 2194456 TI - Human tumor cell lines express low levels of oncomodulin. AB - Different human carcinoma cell lines were screened for the presence of Ca2(+) binding oncomodulin. A specific polyclonal antibody was raised against a synthetic peptide (amino acids 99-108) of oncomodulin coupled to hemocyanin. Extracts of tumor cell lines (several human, one rat) were analyzed for the presence of oncomodulin by immunoblotting. A strong immunoreaction of oncomodulin was obtained in chemically transformed rat fibroblasts (T14c) in contrast to all human tumor cell lines investigated, where no immunoreaction was obtained. These results suggest that oncomodulin cannot be used in diagnostics of human tumors. PMID- 2194457 TI - Insulin provokes apparent increases in rat adipocyte M-kinase. AB - Insulin has been shown to stimulate the translocation of protein kinase C (PKC) in rat adipocytes. Presently, we found that decreases in cytosolic 80 kDa PKC were associated with increases in Ca++/phospholipid-independent protein kinase activity, and increases in a 50 kDa cytosolic protein recognized by anti-PKC antiserum. These findings suggest that insulin provokes increases in M-kinase in rat adipocytes. PMID- 2194458 TI - Evidence for endothelin-1 release from resistance vessels of rats in response to hypoxia. AB - To elucidate further the contribution of endothelin into endothelium-dependent vasoconstriction evoked by hypoxia, we observed endothelin release during hypoxia. Endothelin was detectable in perfusate from mesenteric artery. Immunoreactive endothelin was confirmed as endothelin-1 by a reverse phase-HPLC. Endothelin release increased 4.1 +/- 1.3 to 12.4 +/- 2.0 pg/30 min without changing perfusion pressure. Thirty minutes of hypoxia stimulated endothelin release by 71 +/- 11% (P less than 0.05) and was associated with an elevation of perfusion pressure. These results suggest that endothelin contributes to endothelium-dependent vasoconstriction by hypoxia in mesenteric artery and may play an important role in the local peripheral vascular tone. PMID- 2194459 TI - Discrimination of two angiotensin II receptor subtypes with a selective agonist analogue of angiotensin II, p-aminophenylalanine6 angiotensin II. AB - Angiotensin II receptor binding sites in rat liver and PC12 cells differ in their affinities for a nonpeptidic antagonist, DuP 753, and p-aminophenylalanine6 angiotensin II. In liver, which primarily contains the sulfhydryl reducing agent inhibited type of angiotensin II receptor, which we refer to as the AII alpha subtype, DuP 753 displays an IC50 of 55 nM, while p-aminophenylalanine6 angiotensin II displays an IC50 of 8-9 microM. In PC12 cells, which primarily contain the angiotensin II receptor type whose binding affinity is enhanced by sulfhydryl reducing agents (AII beta), DuP 753 displays an IC50 in excess of 100 microM, while p-aminophenylalanine6 angiotensin II displays an IC50 of 12 nM. p Aminophenylalanine6 angiotensin II binding affinity in liver is decreased in the presence of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) suggesting that this analogue is an agonist. PMID- 2194460 TI - The rheumatoid nodule. PMID- 2194461 TI - How important are T cells in chronic rheumatoid synovitis? PMID- 2194462 TI - In vitro identification of a subpopulation of fibroblasts that produces high levels of collagen in scleroderma patients. AB - A subpopulation of scleroderma dermal fibroblasts was identified by flow cytometric analysis. Between 15% and 25% of the cells within the scleroderma fibroblast lines had high levels of cytoplasmic granularity, as identified by side light scatter characteristics. Similar fibroblasts composed less than 3% of the cells within the normal fibroblast lines, although greater numbers could be induced through exposure to soluble factors derived from activated mononuclear cells. The granular subpopulation of fibroblasts produced 2-3 times as much procollagen as did the other fibroblasts. These data support the hypothesis that fibrosis in scleroderma may result in part from the activity of an inherently high procollagen-producing subset of normal fibroblasts that is expanded through exposure to immune cytokines. PMID- 2194463 TI - Proteoglycan-induced polyarthritis and spondylitis adoptively transferred to naive (nonimmunized) BALB/c mice. AB - Mononuclear cells from BALB/c mice with progressive polyarthritis and spondylitis induced by injection of fetal human articular cartilage proteoglycan (PG) were used to transfer arthritis by intravenous injection into irradiated, nonimmunized syngeneic mice. Successful transfer of arthritis to BALB/c mice required the injection of lymphocytes from mice with arthritis, along with 50 micrograms of human fetal PG, or lymphocytes stimulated in vitro with either fetal human PG or with mouse cartilage PG. In addition, interleukin-2 or immune sera from animals with arthritis significantly reduced the time to onset of transferred disease. The onset of adoptively transferred arthritis, using cells and antigen, from the time of the first injection (38.2 +/- 18.2 days, mean +/- SD) was shortened if lymphocytes from mice with transferred arthritis were reinjected (retransferred) into other, irradiated syngeneic mice (6.1 +/- 2.6 days). The appearance of autoreactive antibodies to mouse cartilage PG in the sera of mice with adoptively transferred arthritis (secondary or tertiary) preceded the appearance of the first clinical symptoms by a few days. The transfer of arthritis was blocked by pretreatment of donor (arthritic) lymphocytes with either anti-T cell or anti-B cell antibodies and complement. Exposure of mononuclear cells from mice with arthritis to PG, and its removal prior to transfer, also resulted in transfer of the arthritis. PG-induced arthritis was not transferred to nonirradiated mice, nor to irradiated mice injected with lymphocytes from animals with primary arthritis without chondroitinase ABC-digested fetal human PG. Arthritis never developed after injection of immune sera from mice with arthritis (without cells), nor when cells of nonarthritic animals were used with chondroitinase ABC digested fetal human PG, with or without interleukin-2. PMID- 2194464 TI - Autoantibodies to lamins in rheumatoid arthritis. AB - The presence of autoantibodies reacting with lamins A and C was demonstrated in sera from 2 patients with rheumatoid arthritis (RA). One patient developed antilamin antibodies several years after being diagnosed as having RA; she was also found to have chronic active hepatitis. The second patient had severe nodular RA. We describe the other serologic findings in these 2 patients and discuss the relationships between antilamin antibodies and RA. PMID- 2194465 TI - Bullous photosensitivity to naproxen: "pseudoporphyria". AB - Pseudoporphyria is a photo-induced cutaneous bullous disease characterized by distinct clinical, histologic, and most recently, immunofluorescent features. By definition, results of porphyrin studies are normal in this disease. We describe here a woman with naproxen-induced pseudoporphyria, and we review previously reported cases of pseudoporphyria. The increasing frequency of pseudoporphyria is a result of the current popularity of nonsteroidal antiinflammatory drugs. Physicians need to be aware of this reversible skin disorder. Pseudoporphyria must be considered and an appropriate evaluation must be done when an individual who is taking nonsteroidal antiinflammatory drugs develops bullae and increased fragility of exposed skin. PMID- 2194466 TI - A randomized clinical trial of rib belts for simple fractures. AB - The authors present a pilot study in which 20 patients with simple rib fractures were randomized prospectively into two treatment groups. One group received ibuprofen and the other group ibuprofen plus a rib belt for analgesia. There were no statistically significant differences observed in pulmonary function testing between the groups at initial visit, 48 hours, or 5 days. Atelectasis developed in four patients, two in each treatment group; there were no cases of pneumonitis. Patients with displaced rib fractures experienced a higher rate of hemo- or pneumothorax than did those with nondisplaced fractures (5/10 v 1/10). Patients with displaced fractures who used rib belts experienced a higher rate of hemothorax than those using oral analgesia alone (4/6 v 1/4). Patients using rib belts uniformly reported a significant amount of additional pain relief. The clinician can use a rib belt to provide additional comfort to the patient with fractured ribs without apparent additional compromise to respiratory parameters. A further study stratifying displaced and nondisplaced fractures has been initiated to clarify the possible contributing roles of displaced rib fractures and the rib belt in patients with displaced fractures. PMID- 2194467 TI - Serum magnesium concentrations after repetitive magnesium cathartic administration. AB - Severe hypermagnesemia has been reported by several authors after multiple doses of magnesium-containing cathartic are administered during management of a toxic ingestion. To evaluate the frequency and magnitude of serum magnesium elevations after the use of repetitive magnesium catharsis, we prospectively evaluated 102 patients who received multiple doses of magnesium citrate as a part of treatment of an overdose. Commonly ingested substances for which repetitive cathartic was administered were tricyclic antidepressants in 47%, aspirin in 17%, and phenytoin in 10%. For each case, serial electrolytes, blood urea nitrogen, creatinine, calcium and magnesium were obtained. Mean initial serum magnesium concentration was 1.8 +/- .03 mEq/L. After a mean 960 mL of magnesium citrate (9.22 g magnesium), final mean serum magnesium concentration was 2.5 +/- .05 mEq/L. Forty seven patients (47%) developed an elevated (greater than 2.4 mEq/L) serum magnesium concentration, with 12 greater than 3.0 mEq/L. No correlation was found between total quantity of magnesium citrate administered and the increment in serum magnesium concentration. Our data indicate that serum magnesium concentrations consistently rise after repetitive magnesium citrate use. However, the magnitude of this rise appears modest. The elevation in serum magnesium concentration does not correlate with the quantity of magnesium administered. We conclude that with close monitoring, repetitive magnesium citrate can be administered without inducing severe hypermagnesemia (serum magnesium concentration greater than 5.0 mEq/L). PMID- 2194468 TI - Hepatic abscess resulting from gastric perforation of a foreign object. AB - A case of a patient with a hepatic abscess secondary to a fish or chicken bone is presented. Of interest is the fact that the abscess resulted from gastrointestinal perforation of the foreign object. A review of the literature of this unusual occurrence along with clues to making the diagnosis are discussed. PMID- 2194469 TI - Diagnostic difficulties of foreign body aspiration in children. AB - A case of a 4-year-old child who aspirated a 22-caliber bullet is presented to illustrate the variability of signs and symptoms of foreign body aspiration. Despite the large size of the bullet, cough, dyspnea, and wheezing were absent on presentation. Chest roentgenogram confirmed the diagnosis of a radiopaque bronchial foreign body. A retrospective review of 42 additional children with foreign body aspiration showed 8 (19%) were unwitnessed, 24 (57%) were asymptomatic at presentation, 8 (19%) had normal physical examinations, and 10 (24%) had normal inspiratory/expiratory chest roentgenograms. This demonstrates the importance of considering bronchoscopy for any child who presents with a history of possible foreign body aspiration, but is asymptomatic and has normal roentgenographic findings. PMID- 2194470 TI - Treatment of tooth avulsion in the emergency department: appropriate storage and transport media. AB - Teeth that have been accidentally avulsed can be preserved, reconstituted, and replanted with an excellent long-term retention prognosis. The mechanisms for this process are now well understood. The most biologic methods for preserving and storing avulsed teeth are presented so that the emergency physician can choose appropriate modalities for treating patients who present with this problem. PMID- 2194471 TI - Peer review of the biomedical literature. AB - Peer review is the assessment by experts of material submitted for publication. The peer reviewer serves the editor by substantiating the quality of the manuscript, and serves the author by giving constructive criticism. This system has benefits and drawbacks, including the tendency to select against novel work. Reviewers, whose work is generally unpaid, tend to be academicians who review for several journals and are authors and editors themselves. Editors often blind reviewers to authors to reduce bias, but reviewers frequently recognize the author anyhow. Blinding authors to reviewers may protect the reviewer. Manuscripts rejected by one journal because of peer review are usually published in another. Since peer review serves to validate the quality of the biomedical literature, the process should be valid itself. PMID- 2194472 TI - Whither biophysics? PMID- 2194473 TI - Crystallography of biological macromolecules at ultra-low temperature. PMID- 2194474 TI - Calorimetrically determined dynamics of complex unfolding transitions in proteins. PMID- 2194475 TI - The structure and function of the aspartic proteinases. PMID- 2194476 TI - Mechanisms of cytoplasmic hemoglobin and myoglobin function. PMID- 2194477 TI - Uniform and selective deuteration in two-dimensional NMR of proteins. PMID- 2194478 TI - Mechanisms of long-distance electron transfer in proteins: lessons from photosynthetic reaction centers. PMID- 2194479 TI - Electrostatic interactions in macromolecules: theory and applications. PMID- 2194480 TI - Spectroscopic analysis of genetically modified photosynthetic reaction centers. PMID- 2194481 TI - On the microassembly of integral membrane proteins. PMID- 2194482 TI - Ion distributions around DNA and other cylindrical polyions: theoretical descriptions and physical implications. PMID- 2194483 TI - NMR studies of metabolism. PMID- 2194484 TI - Obituary: Hans Grisebach 1926-1990. PMID- 2194485 TI - Paradoxes of pertussis toxin. PMID- 2194486 TI - On the structure of the epidemic spread of AIDS: the influence of an infectious coagent. AB - The reported AIDS cases in the USA and the Federal Republic of Germany are growing almost exponentially. Considering the epidemiological curves for different risk groups (homosexual men, i.v. drug abusers, heterosexual partners etc.) it is extremely surprising, that nearly exactly the same development occurs in all risk groups. One only has to consider a certain time shift for each group. The conformity of the development for all groups is evident by the fact, that the curves representing the reported AIDS cases for different risk groups are straight lines (in a logarithmic scale) running nearly exactly in parallel. This remarkable parallelism can be understood only if the spread of AIDS is independent of the sexual or drug risk in a certain sense. On the other hand, the drastic overrepresentation of the sexually highly active groups and drug abusers in the number of AIDS cases obviously requires that the transmission of AIDS unequivocally depends on the sexual and drug risk. We present a mathematical model that is suitable to reconcile this apparent contradiction in the interpretation of the epidemiological data: the observed parallel time series for the spread of AIDS in groups with different risk of infection can be realized by computer simulation, if one assumes that the outbreak of full-blown AIDS only occurs if HIV and a certain infectious coagent (cofactor) CO are present. Such a situation is not uncommon, see, e.g. the influenza virus--Staphylococcus aureus system. According to the mathematical model this cofactor would spread independently of the sexual and drug risk--in contrast to HIV. However, due to its analytical properties the simulated cofactor cannot be identified so far with any known infectious agent. PMID- 2194488 TI - Malformations in monozygotic twins--two case histories. PMID- 2194487 TI - Ultrasound of the acute abdomen--Part I. PMID- 2194489 TI - Gastric motility--the role of ultrasound. PMID- 2194490 TI - An unusual case of congenital dislocation of the hips. PMID- 2194491 TI - Ultrasound of the acute abdomen--Part II. PMID- 2194492 TI - The radiologic evaluation of renal metastases. AB - Renal metastases can arise from practically any primary neoplasm and should no longer be considered rare. Such lesions are usually detected during surveillance US or CT examinations. Appearances favoring metastases over an additional renal carcinoma are multiplicity, bilaterality, metastatic disease elsewhere, and perinephric disease. Since not all renal metastases behave predictably and may even appear as single, exophytic lesions, guided fine-needle aspiration may be required when such information will alter patient management. PMID- 2194493 TI - Percutaneous transhepatic biliary drainage: a review. AB - Percutaneous transhepatic biliary drainage (PTBD) was conceptualized more than 35 years ago, but its clinical application only flourished in the past 10 years after a number of technical refinements. Initially it was used primarily as a means of providing palliative decompression for patients with malignant biliary obstructions. Despite a number of well-recognized problems associated with its long-term use, including relatively high prevalences of cholangitis and other catheter-related complications, PTBD remains a viable treatment for patients with advanced malignancies where few therapeutic alternatives exist. In recent years, PTBD has increasingly been employed in the management of benign biliary diseases. Since only short-term drainage is required in the majority of patients with benign diseases, much of the catheter-related complications can be avoided. Through the transhepatic tract created by PTBD, various therapeutic manipulations can be performed, including biliary lithotripsy, stricture dilatation, and sphincterotomy. The impact of PTBD in the management of benign biliary diseases is expected to increase with the development of more sophisticated transhepatic instruments and techniques. In this article, the technique and complications of PTBD are described, followed by a review of the applications of PTBD in both malignant and benign biliary diseases. PMID- 2194494 TI - Radiology of hepatic transplantation. AB - Hepatic transplantation is now a relatively commonplace procedure, performed at many institutions around the world. Assessment of transplant candidacy and posttransplantation complications relies heavily on radiologic studies. After transplantation, radiographic evaluation is especially important as the clinical presentation and laboratory findings of many complications are nonspecific. Additionally, therapeutic radiologic intervention is often beneficial in the management of posttransplantation complications. This article reviews the role of imaging in hepatic transplantation. It focuses on the capabilities of noninvasive and invasive imaging modalities in the evaluation of potential hepatic transplant candidates and in hepatic recipients, and it also reviews the application of interventional radiologic procedures to posttransplantation complications. PMID- 2194495 TI - Conformational transitions of polynucleotides in the presence of rhodium complexes. AB - We studied the effects of hexammine and tris(ethylene diamine) complexes of rhodium on the conformation of poly(dG-dC).poly(dG-dC) and poly(dG-m5dC).poly(dG m5dC) using spectroscopic techniques and an enzyme immunoassay. Circular dichroism spectroscopic measurements showed that Rh(NH3)6(3+) provoked a B-DNA--- Z-DNA----psi-DNA conformational transition in poly(dG-dC).poly(dG-dC). Using the enzyme immunoassay technique with a monoclonal anti-Z-DNA antibody, we found that the left-handedness of the polynucleotide was maintained in the psi-DNA form. In addition, we compared the efficacy of Rh(NH3)6(3+) and Rh(en)3(3+) to provoke the Z-DNA conformation in poly(dG-dC).poly(dG-dC) and poly(dG-m5dC.poly(dG-m5dC). The concentrations of Rh(NH3)6(3+) and Rh(en)3(3+) at the midpoint B-DNA----Z-DNA transition of poly(dG-dC).poly(dG-dC) were 48 +/- 2 and 238 +/- 2 microM, respectively. The psi-DNA form of poly(dG-dC).poly(dG-dC) was stabilized at 500 microM Rh(NH3)6(3+). With poly(dG-m5dC).poly(dg-m5dC), both counterions provoked the Z-DNA form at approximately 5 microM and stabilized the polynucleotide in this form up to 1000 microM concentration. These results show that trivalent complexes of Rh have a profound influence on the conformation of poly(dG dC).poly(dG-dC) and its methylated derivative. Furthermore, the Rh complexes are capable of maintaining the Z-DNA form at concentration ranges far higher than that of other trivalent complexes. Our results also demonstrate that the efficacy of trivalent inorganic complexes to induce the B-DNA to Z-DNA transition of poly(dG-dC).poly(dG-dC) and poly(dG-m5dC).poly(dG-m5dC) is dependent on the nature of the ligand as well as the polynucleotide modification. Differences in charge density and hydration levels of counterions or base sequence- and counterion-dependent specific interactions between DNA and metal complexes might be possible mechanisms for the observed effects. PMID- 2194496 TI - Secondary structures of Tetrahymena thermophila rRNA IVS sequence involved in its self-splicing reactions: a new computer analysis. AB - The secondary structures of Tetrahymena thermophila rRNA IVS sequence involved in the self-splicing reactions, are theoretically investigated with a refined computer method previously proposed, able to select a set of the deepest free energy RNA secondary structures under constraints of model hypotheses and experimental evidences. The secondary structures obtained are characterized by the close proximity of self-reactions sites and account for double mutations experiments, and differential digestion data. PMID- 2194497 TI - Translation-initiation promoting site on transcripts of highly expressed genes from Saccharomyces cerevisiae and the role of hairpin stems to position the site near the initiation codon. AB - It is reported that the AUG-upstream region on mRNAs of highly expressed genes from S. cerevisiae invariably possesses a translation-initiation promoting site, that can base pair with a well-conserved site on 18S rRNA during the formation of 40S initiation complex. Weak hairpin stem in the mRNA region between such a site and the initiation codon brings the site nearer to the initiation codon and also extends the length of base pairing. Such a base pairing can lead to a comparatively more stable 40S initiation complex, resulting in a higher rate of formation of the 80S initiation complex and consequently in an enhancement of the rate of initiation of translation. The site on 18S rRNA can interchange its base pairing between the site on mRNA and a well-conserved site on 25S rRNA in the formation of the 80S initiation complex. PMID- 2194498 TI - Distribution and colocalization of delta sleep-inducing peptide and luteinizing hormone-releasing hormone in the aged human brain: an immunohistochemical study. AB - The distributions of delta sleep-inducing peptide (DSIP)- and luteinizing hormone releasing hormone (LHRH)-immunoreactive neurons were investigated in the human brain with special emphasis on the basal forebrain (from the septum to the hypothalamus), using indirect immunofluorescence. With a modified elution technique, sequential stainings on the same section showed that DSIP- and LHRH immunoreactivities were often colocalized. Small numbers of LHRH/DSIP immunoreactive cells were essentially detected in the diagonal band of Broca, the medial septum and the ventral hypothalamus. The richest areas displaying fibres and terminal-like structures were the preoptic area, the ventromedial and ventrolateral hypothalamic areas, the periventricular region and certain circumventricular organs (i.e. median eminence, vascular organ of the lamina terminalis). Few isolated fibres were observed in the subfornical organ. The topographical relationships between DSIP- and LHRH-immunoreactivities in the neurosecretory systems suggest that DSIP may play a role as important as that of LHRH. PMID- 2194499 TI - Research funding: a disclosure item. PMID- 2194500 TI - Recombinant targeted proteins for biotherapy. AB - In an effort to improve existing biotherapies, researchers have used recombinant techniques to alter the structure of toxins, monoclonal antibodies, and other receptor and effector molecules. Experimental research has demonstrated that the extent of problems such as nonspecific toxicity and rapid clearance by the immune system are not as great with genetically engineered toxins as opposed to native toxins. Fusion proteins, which combine portions of toxins, antibodies, or various effector molecules, exhibit the preferred biologic properties of their constituents. Unlike their murine counterparts, chimeric antibodies have the ability to invoke cell-mediated immunity and are less immunogenic to humans. Because they display different antigen-binding specificities on the same molecule, hybrid hybridomas are a potential means of juxtaposing effector cells or toxins to tumor cells. These and other positive features of recombinant proteins offer a decided advantage over previous biotherapeutic agents, and these molecules are expected to find application in the treatment of cancer, the acquired immunodeficiency syndrome, and autoimmune diseases. PMID- 2194501 TI - Therapeutic activities of PHA-L4, the mitogenic isolectin of phytohemagglutinin. AB - Evidence is presented that suggests that PHA-L4 may exert the therapeutic effects of a theoretical ideal biological response modifier through its ability to do the following: to assist remission induction in certain malignancies, to exhibit direct antitumor cytotoxic effects, to enhance antineoplastic effect of radiation and chemotherapy, to decrease the liability to malignant transformation, to promote differentiation and restore normal growth responses in neoplastic cells, to manifest minimal liability to suppressor activity that would inhibit tumor rejection or antitumor cytotoxicity, to repress graft rejection and graft-versus host responses and amplify the immunosuppressive effects of other agents in allograft transplantations, to display a direct protective effect against damage from radiation and chemotherapy, to stimulate normal myelopoiesis, to reinforce responses against various infections, to amplify tumor immunogenicity, and to attract mononuclear cells to sites of injection or local application. PMID- 2194502 TI - Interaction between nonsteroidal anti-inflammatory drugs and high-dose methotrexate: a literature review. AB - An important step in preventing methotrexate (MTX) toxicity is to assess patient self-medication of over-the-counter drugs before high-dose methotrexate (HD-MTX) treatment is administered. Nonsteroidal anti-inflammatory drugs given within a 10 day period before a patient receives HDMTX leads to a decreased MTX excretion rate causing MTX toxicity. Education of the nursing staff and patients and their families is vital to avoid the potentially dangerous effects of a delayed MTX excretion rate. PMID- 2194504 TI - Overview of childhood cancer: clinical trials and cooperative groups. PMID- 2194503 TI - Pediatric cancer nursing research priorities: a Delphi study. PMID- 2194505 TI - Clinical uses of interferons, interleukins, tumor necrosis factor, monoclonal antibodies, and growth factors in patients with cancer. PMID- 2194506 TI - Granulocyte-macrophage colony-stimulating factor: a teaching program for staff and patients. PMID- 2194507 TI - Pain and anxiety management program for pediatric oncology patients. PMID- 2194508 TI - Insulinemia and blood pressure. Relationships in patients with primary and secondary hypertension, and with or without glucose metabolism impairment. AB - In order to investigate the relationships between insulinemia and hypertension, fasting insulinemia has been assessed in 117 subjects: 69 normotensive subjects, 36 with essential hypertension, and 12 with renovascular hypertension, all untreated and newly diagnosed, classified in subgroups (euglycemic nonobese, euglycemic obese, with impaired glucose tolerance and with non-insulin-dependent diabetes mellitus). In the patients with essential hypertension fasting insulinemia was significantly higher than in normotensive subjects (P less than .0005). The patients with secondary hypertension and the normotensive subjects had similar fasting insulinemia values. In each subgroup fasting insulinemia was higher in hypertensive patients than among normotensive subjects (P less than .05). A significant correlation between fasting insulinemia and mean blood pressure has been found in patients with essential hypertension (r = 0.408, P less than .05), but not in patients with renovascular hypertension. Our data suggest a possible direct relationship between fasting insulinemia and blood pressure, especially in obese patients or patients with impaired glucose metabolism, and that increased blood pressure per se is not an insulin resistant state. PMID- 2194509 TI - Effect of low fat-high carbohydrate diets in hypertensive patients with non insulin-dependent diabetes mellitus. AB - Effects of variations in dietary fat and carbohydrate content on various aspects of glucose, insulin, and lipoprotein metabolism were evaluated in 11 patients with hypertension, who also had non-insulin-dependent diabetes mellitus (NIDDM). All of these patients were being treated with sulfonylureas, thiazides, and beta adrenergic receptor antagonists. The comparison diets contained either 40 or 60% of total calories as carbohydrate, with reciprocal changes in fat content from 40 to 20%. The diets were consumed in a random order for 15 days in a crossover experimental design. The ratio of polyunsaturated to saturated fat and total cholesterol intake were held constant in the two diets. Plasma glucose and insulin concentrations were significantly (P less than .001) elevated throughout the day when patients consumed the 60% carbohydrate diet. Fasting plasma total and very-low-density lipoprotein (VLDL) and triglyceride (TG) concentrations increased by 30% (P less than .001) after 15 days on the 60% carbohydrate diet. Total plasma cholesterol concentrations were similar on both diets, as were low density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol concentrations. PMID- 2194511 TI - Increased erythrocyte magnesium in never treated essential hypertension. AB - In the present study we aimed at evaluating the intracellular concentrations of magnesium, potassium and sodium in 50-year-old, otherwise healthy white men with never treated, essential hypertension (n = 12) and in normotensive control subjects (n = 12) matched for age, sex, race, height, weight and smoking habits. Intraerythrocyte magnesium was significantly increased in the hypertensive group (P less than .001) and correlated positively and significantly to blood pressure in the total group (P less than .01). The intracellular potassium to sodium ratio tended to be lower in the hypertensive group (P less than .05). Thus, the present study supports increased intracellular magnesium probably unrelated to intracellular potassium-sodium imbalance in never treated, essential hypertension. PMID- 2194510 TI - Time-related changes in plasma adrenal steroids during treatment with spironolactone in primary aldosteronism. AB - Time-related changes in plasma levels of aldosterone, deoxycorticosterone, corticosterone, and cortisol were studied during treatment with spironolactone in 8 patients with primary aldosteronism due to adenomas. Plasma renin activity (PRA), serum sodium and serum potassium were also measured. The patients were treated with spironolactone, 75 to 225 mg daily, and blood samples were withdrawn on days 7, 14, and 21 to 28 of drug administration. Plasma aldosterone concentrations (PAC) were not altered by spironolactone; however, significant increases were observed in plasma deoxycorticosterone on days 21 to 28 and in plasma corticosterone and cortisol on days 14 and 21 to 28. The suppressed PRA values were markedly increased on days 21 to 28 and low levels of serum potassium returned to the normal range on day 7. The lack of increase in PAC, despite a remarkable rise in PRA and serum potassium, suggests biosynthetic inhibition of spironolactone at the sites of 18-hydroxylation and/or 18-oxidation, because of the elevation of deoxycorticosterone and corticosterone. PMID- 2194512 TI - Correctable subsets of primary aldosteronism. Primary adrenal hyperplasia and renin responsive adenoma. AB - Among 154 cases of primary aldosteronism seen in the General Clinical Research Center at San Francisco General Hospital, twelve patients did not fulfill established characteristics of an aldosterone producing adenoma (APA) or idiopathic hyperaldosteronism (IHA). Eight patients had nodular adrenocortical hyperplasia; plasma and urinary aldosterone were elevated and responses to stimulatory and suppressive maneuvers demonstrated the same autonomy seen in patients with APA. This subset is designated primary adrenal hyperplasia. Four additional patients also had elevated aldosterone levels that were responsive to these maneuvers, similar to IHA, but had unilateral tumors. This group has been designated as aldosterone-producing renin-responsive adenoma. Eleven patients had unilateral adrenalectomy and one preferred prolonged spironolactone therapy, resulting in a sustained cure or amelioration of hypertension, hypokalemia and normalization of aldosterone production. PMID- 2194513 TI - The captopril challenge for renovascular hypertension. PMID- 2194514 TI - Walther Birkmayer--a tribute on his 80th birthday. PMID- 2194515 TI - Hormonal changes in hemodialysis. AB - When chronic renal failure becomes advanced, the serum or tissue levels and/or the functions of most hormones are altered because of several interplaying mechanisms involving synthesis, transport, accumulation of inhibitors, abnormality of target organ responsiveness, and impaired renal clearance. As regular dialysis treatment is performed, most of these uremic hormone abnormalities are not reversed, and some of them may even get worse. The main endocrine derangements can be grouped as sexual hormone dysfunction, thyroid abnormalities, growth retardation, hormone-related disorders of metabolism, derangements of pressor substances, gastrointestinal peptide abnormalities, renal osteodystrophy, and anemia. The endocrine abnormalities play a major role as for the clinical and metabolic rehabilitation of dialysis patients. PMID- 2194516 TI - Endocrine abnormalities in patients treated by continuous ambulatory peritoneal dialysis. AB - Endocrine-metabolic disturbances of renal failure have many underlying mechanisms, including abnormal secretion, transport, and target cell binding, impaired synthesis and elimination by the diseased kidney, and responses to stimuli resulting from altered homeostasis. Neither hemodialysis nor continuous ambulatory peritoneal dialysis (CAPD) removes large amounts of hormones. By correcting metabolic, fluid and electrolyte disturbances, dialysis may improve some endocrine abnormalities. Possibly because of more permeable membranes, or continuous treatment including ultrafiltration, CAPD has a somewhat more salutary effect on uremic endocrinopathy than hemodialysis. In particular, hormonal regulation of salt and water balance, erythropoietic function, female reproductive function, and some aspects of renal osteodystrophy respond more favorably to CAPD. The endocrine response suggests that there is no inferiority of CAPD as a treatment for renal failure. PMID- 2194517 TI - Endocrine alterations in kidney transplant patients. AB - Several factors are involved in the persistence of endocrine alterations after renal transplantation, among which the following are to be mentioned: (1) duration of chronic uraemia before renal transplantation; (2) residual function of the patients' native kidneys; (3) quality of function of the renal graft; (4) modulation of secretion, transport, and degradation of hormones, and/or (5) altered target organ responsiveness to hormones induced by immunosuppressive drugs (glucocorticoids, azathioprine, cyclosporin A) or altered internal environment. In kidney transplant patients the following endocrine abnormalities are to be mentioned: dissociation of the physiological relationship between aldosterone synthesis and function of the renin-angiotensin system, abnormal volumetric regulation of arginine vasopressin secretion, suppressed responsiveness of cortisol secretion to stimulatory manoeuvres, persistent secondary hyperparathyroidism, relative deficiency of insulin (induced by glucocorticoid therapy), with consequent carbohydrate intolerance or even diabetes mellitus, suppressed response of gastrin and pancreatic hormone secretion to a test meal, and reduced responsiveness of atrial natriuretic peptide secretion to central hypervolaemia. Episodes of acute graft rejection are characterized by endocrine alterations similar to those seen in patients with acute or chronic renal failure. PMID- 2194518 TI - Wound healing. Relationship of wound closing tension to scar width in rats. AB - A study was conducted to better define the relationship between closing tension and the resulting scar width of incisional wounds. Five groups of 10 hairless rats each were studied. Transverse wounds were created and closed on the back of each rat, with closing tension varied by excising amounts of skin in widths of 0 (control), 15, 30, 45, and 60 mm. At 28 days, the scar width was measured by three methods: digital caliper, photographically, and histologically. Results showed that wounds closed under the highest tension (60-mm excision group) had significantly wider scars than controls by all three measurement techniques. Regression analysis of the caliper scar width as determined by squaring the closing tension resulted in a nonlinear equation resembling an exponential curve that "best fit" the variables. PMID- 2194519 TI - Immunologic and pathophysiologic role of tumor necrosis factor. PMID- 2194520 TI - Immunohistochemical detection of intracellular tropoelastin: an assay for elastin production and its use in the detection and assessment of elastogenic factors. AB - Techniques are described for visualizing intracellular tropoelastin at the light level using immunofluorescence and immunogold techniques. Best results were obtained with B5 fixative on cells permeabilized with acetone. Using either formaldehyde or paraformaldehyde for fixation (instead of B5) resulted in both less reproducible and less intense intracellular staining, and permeabilization of the cells with ethanol resulted in relatively high background staining compared with that obtained with cold (-20 degrees C) acetone. Intracellular tropoelastin was seen most prominently in the perinuclear region, and the intensity of staining agreed with the reported rate of tropoelastin synthesis as assayed by enzyme-linked immunosorbent assay (ELISA) and RNA hybridization studies. The applicability of the intracellular staining technique for studying the elastin phenotype was tested by demonstrating increases in both the number of positive cells and in the intensity of elastin staining in cells treated with smooth muscle elastogenic factor (SMEF), an elastogenic factor known to stimulate elastin production. PMID- 2194522 TI - Mechanisms of cell toxicity. PMID- 2194521 TI - Protein kinase C and tumor promoters. AB - The complexity of PKC has made it difficult to define the precise biochemical processes associated with the various PKC-related cellular responses observed. In the past year, we have seen progress in complementary approaches that are helping to solve the puzzles. These include purification and characterization of individual isozymes, expression of normal and mutant PKCs, immunolocalization, and identification of specific activators and inhibitors. All of these will be useful in identifying the primary targets of PKC phosphorylation and their function. PMID- 2194523 TI - Yeast cell cycle. PMID- 2194524 TI - Lower eukaryotic cell cycle: perspectives on mitosis from the fungi. PMID- 2194525 TI - Abbreviated and regulated cell cycles in Drosophila. PMID- 2194526 TI - Control of DNA replication. PMID- 2194527 TI - Periodic events in the cell cycle. PMID- 2194528 TI - Control of mammalian cell proliferation. PMID- 2194529 TI - Centrosomes: composition and reproduction. PMID- 2194530 TI - Cell multiplication. PMID- 2194531 TI - Current status of epirubicin (Farmorubicin) in the treatment of solid tumours. AB - Epirubicin (Farmorubicin) is a drug of significant interest in the treatment of a variety of solid tumours and a comprehensive review of reported investigations is given. From experimental and clinical studies it appears that in general doxorubicin and epirubicin exhibit no qualitative, but only some quantitative, differences. Thus, the pharmacokinetic and pharmacodynamic characteristics of the two drugs are essentially similar, as are the tumour spectrum and the level of their clinical efficacies. To achieve haematological equitoxicity of the two drugs the dose of epirubicin should be approximately 20% higher than that of doxorubicin, giving rise to a higher cumulative dose of epirubicin. On the other hand, epirubicin is significantly less cardiotoxic than doxorubicin. Thus, the recommended cumulative dose of doxorubicin is 500 mg/m2 and the corresponding figure for epirubicin is 1,000 mg/m2. For either drug a number of questions are still left open, the most important of which include the questions about optimal treatment schedules and the existence of a clinical relevant dose/efficacy relationship. PMID- 2194532 TI - Natural history of breast cancer. AB - The natural history of breast cancer has been, and will be, extremely hard to study. Indirect evidence suggests that any cancer cell population may be phenotypically unique with multiple abnormal traits which decisively forge the clinical behavior. Histopathologic grouping will only give a very imperfect reflection of phenotypical individuality. It is proposed that essential determinants of the subsequent behavior have already been fixed during the induction period, i.e. long before the clinical debut. This may to some extent be reflected by the DNA content of the tumor cells. Metastases to axillary lymph nodes is strongly determined by size of primary tumor according to a function which suggests a smooth linear risk for lymphatic spread over a broad size interval. It is suggested that each cell of any given cancer may be endowed with a small chance of dissemination to axillary lymph nodes which may be essentially constant during the entire natural life history. Number of cancer cells of the primary tumor would then be the decisive determinant for risk of metastatic dissemination. It is not necessary to invoke qualitative progression from 'non metastasibility' to 'metastasibility'. Small differences exist in the natural history of different histological types of breast cancer. PMID- 2194534 TI - Drug sensitivity testing of human breast cancer. AB - A survey of drug sensitivity testing of human breast cancer is given. The purpose of sensitivity testing, the tumour material studied, and the various in vivo and in vitro assays that are being used are discussed. Moreover, examples of results obtained are presented. PMID- 2194533 TI - Oncogenes and tumor growth factors in breast cancer. A minireview. AB - Five oncogenes have been implied as having a role in human breast tumorigenesis: int-2, c-erbB-2 (HER-2), c-myc, c-Ha-ras and the recessive Rb-1. As far as the function and biochemistry of these oncogenes have been studied, they act at different levels and have totally different functions in the cells. They are normally cellular genes, likely to have important functions in normal cell growth or differentiation. In the tumors their regulation or function is altered, due to a wide class of mutations. The oncogenes may cooperate to result in the malignant cell phenotype. However, different oncogenes are mutated in different tumors, so that the tumors show a variable pattern at the molecular level, underlining the individuality of these tumors already described as differences in histopathology, hormone receptor expression and clinical course. The main importance of the oncogene studies is still to reveal basic pathogenetic mechanisms. When appropriate it is important to test diagnostic or prognostic significance of the oncogene mutations. PMID- 2194535 TI - New cytotoxic drugs in treatment of breast cancer. AB - Over the past 5-10 years approximately 40 new drugs have been evaluated for their efficacy in patients with advanced breast cancer, usually heavily pretreated. Among 9 anthracyclines and anthracycline analogs, epirubicin, idarubicin and mitoxantrone have demonstrated activity which justifies their introduction into clinical practice. Efficacies of epirubicin and doxorubicin are similar and slightly superior to that of mitoxantrone, whereas mitoxantrone is less toxic. Randomized comparisons of doxorubicin or epirubicin versus idarubicin have yet to be conducted. Among 36 non-anthracycline analogs tested only vindesine and cisplatinum have been associated with activities which deserve further studies. PMID- 2194536 TI - How to improve cytotoxic therapy in advanced breast cancer. AB - The optimal cytotoxic treatment of patients with advanced breast cancer is so far not defined. Median survival after first metastatic manifestation is approximately 18 months. No direct evidence for a survival improvement after the introduction of cytotoxic therapy has been published. Major effects have been made to improve treatment efficacy through manipulations of doses, schedules and combinations of known cytotoxic drugs. Three months is probably too short a treatment period. Alternating non-cross resistant regimens offer no advantage over sequential therapy. A dose-response relationship clearly exists in breast cancer, but the higher response rates have not been transformed into a survival benefit. Treatment of advanced breast cancer is palliative, and if, furthermore, we have actually reached a plateau where no further improvement in survival is possible, we will have to evaluate every new treatment modality carefully according to quantity as well as quality of life. PMID- 2194537 TI - Clinical trials in locally advanced breast cancer. AB - Survival after treatment of locally advanced breast cancer is poor and resembles that for untreated breast cancer. Although retrospective comparisons have suggested that the addition of systemic treatment might be beneficial, a literature survey of the controlled clinical trials failed to show consistent survival benefits of any treatment modality. The local control, or time to local progression, on the other hand seems to be improved by increasing the dose of radiotherapy, or by the addition of endocrine or cytostatic treatment. Further studies should be undertaken to find better means to subdivide patients in different treatment groups. Since the present treatment modalities are unlikely to improve survival more than marginally, clinical studies are necessary to search for the best palliative treatment, until experimental work provides us with better treatment tools. PMID- 2194538 TI - Endocrine therapy of breast cancer. A background. PMID- 2194539 TI - New endocrine drugs for treatment of advanced breast cancer. AB - Current status of endocrine treatment for breast cancer is reviewed. Several new aromatase inhibitors as well as antiestrogens are being introduced for clinical trials. As different drugs within the same drug group may possess different biochemical actions, apart from being useful drugs for treatment of breast cancer, these drugs may also extend our knowledge about the endocrinology of breast cancer. PMID- 2194540 TI - How to improve endocrine therapy of breast cancer. AB - The characteristics of endocrine therapy have made it a standard therapy in metastatic breast cancer. Principles for endocrine therapy in the advanced situation are discussed. Recent overviews have shown a definite, although limited effect also in the adjuvant situation. Three possible ways for further improvement of endocrine therapy are discussed. Firstly, the relevance of results with endocrine therapy in advanced disease for the adjuvant situation is challenged. It is suggested that the most meaningful parameter to look for in the metastatic situation might still be the response rate. Secondly, the question is raised of more reliable predictors of effect of endocrine therapy. A possible model for testing in a neoadjuvant setting in operable cancers is suggested. Thirdly, selection criteria for drugs used in endocrine treatment are discussed, in relation to proven efficacy and short-term and long-term toxicity. As endocrine therapy in the future will probably be more frequently used in patients with better prognosis, the aspect of long-term toxicity will be of major concern. PMID- 2194541 TI - Measurement of quality of life in advanced breast cancer. AB - Before the twentieth century the treatment of advanced breast cancer comprised either willful neglect or futile mastectomy. Recent years have seen the introduction of therapies capable of shrinking disease volume although the concept of a cure still remains remote. Many of these treatments are unpleasant and the burden they force the patient to bear may not be compensated by the reduction in tumour size. Decisions on the value of initiating or continuing such treatment have been taken by the clinician largely since no suitable instruments have been available to measure individual 'quality of life'. Several means have now evolved and in advanced breast cancer, where the treatment may profoundly affect the patient's sense of wellbeing, effort is being made to find out how much. PMID- 2194542 TI - [CT findings of the temporal bones in Waardenburg's syndrome]. AB - We reported three cases of Waardenburg's syndrome and discussed CT findings of the temporal bones. Two cases of these patients were mother and daughter. Case 1, a two-year-old girl, had lateral displacement of the medial canthi, a broad nasal root, hetero-chromic iridis, left ptosis, albinotic fundus, and bilateral congenital deafness. CT findings of the temporal bones showed enlarged vestibules, short lateral semicircular canal, and absent right posterior semicircular canal. The mother had congenital deafness, heterochromia iridis, and a white forelock and showed similar abnormal CT findings of the temporal bones. Case 2, a one-year-old boy, had lateral displacement of the medial canthi, a broad nasal root, partial heterochromia iridis, albinotic fundus, and bilateral congenital deafness. CT findings of the temporal bones showed enlarged vestibules and absence of semicircular canals except the right lateral semicircular canal. These cases were diagnosed as Waardenburg's syndrome on the basis of the characteristic features. PMID- 2194543 TI - [Clinical and biochemical studies in a case of acute encephalopathy associated with calcium hopanthenate administration]. AB - A case with acute disturbance of consciousness associated with calcium hopanthenate (HOPA) administration was reported. He was a 3-year-old boy with autistic developmental delay, had orally taken 1.5 g of HOPA daily for 3 months. Clinical manifestations consisted of fever, vomiting and coma. Laboratory examination revealed severe hypoglycemia and metabolic acidosis, but there were no hepatic enzyme abnormalities. Analysis of urinary organic acid profile showed that very large amounts of medium and long chain dicarboxylic acids and omega-1 hydroxy-fatty acids were excreted. In particular, 2-hydroxysebacic acid, the accumulation of which has only been reported in the urine of patients with Zellweger syndrome and neonatal adrenoleukodystrophy (NALD), was observed. Analysis of urinary acylcarnitines showed that acetylcarnitine was predominant and C6-C10 dicarboxylic acylcarnitines were also excreted. He was treated with and rapidly responded to intravenous glucose and bicarbonate. After withdrawal of the drug he has had no problems and dicarboxylic aciduria disappeared. A CT scan showed symmetric, low density areas in periventricular white matter, especially around the posterior horns of the lateral ventricles. A T2-weighted MRI scan revealed high-intensity signal in the white matter corresponding to areas of low density on CT scan. We conclude that that a large amount of HOPA administration may cause encephalopathy by the inhibition of both mitochondrial and peroxisomal beta-oxidation. PMID- 2194544 TI - [Geriatric otorhinolaryngology]. PMID- 2194545 TI - [Vestibular neurectomy]. PMID- 2194546 TI - [Autologous muscle tissue for reconstruction of the heart and assisted circulation]. PMID- 2194547 TI - [Preservation of the lungs]. PMID- 2194548 TI - [Successful correction of aortopulmonary and ventricular septal defects in an infant under 1 year of age]. PMID- 2194549 TI - [Plastic surgery of major defect of the ventricular septum complicated by complete atelectasis of the left lung in an infant]. PMID- 2194550 TI - Three-dimensional structure of the rat intestinal wall (mucosa and submucosa). AB - The three-dimensional organization of the mucosa and submucosa of the rat intestine was analysed by scanning electron microscopy (SEM) aided by micro dissection methods. New functional aspects raised by the SEM observations were examined by transmission electron microscopy (TEM). Morphogenesis of the intestinal villi was also illustrated three dimensionally. Removal of the epithelium by osmic acid maceration revealed the presence of many round fenestrations averaging 3 microns in diameter over the villous basal lamina. TEM confirmed that they were not artifacts but represented passages or tracks of cells of the immune system such as lymphocytes, eosinophils and macrophages. Penetration of the epithelial processes into the lamina propria was also observed. Close contacts between these free cells and the epithelial cells suggest an intercellular communication between these different cell types. The basal lamina is thus appears as a structure that allows dynamic interaction between the epithelial layer and the lamina propria, though it is generally regarded as a rigid structure acting as a barrier. Beneath the basal lamina, a cellular reticulum of fibroblast-like cells overlies the capillary network in the villi. These cells are characterized by bundles of actin filaments and contact with each other by gap junctions. This cellular reticulum probably influences the absorption of nutrients from the villi by its contractile ability in addition to its supportive role. A similar cellular network occurs beneath the epithelium of the intestinal glands. These cells may also mechanically support the glandular organization, maintaining the delicate microvascular bed. The submucosa is considered the skeleton of the intestine. SEM reveals the main framework of the submucosa is as being composed of two sets of collagen fibers running diagonally around the intestinal wall, one set in a clockwise direction, the other, counterclockwise. These fibers--in different arrays--interweave to form a lattice sheet, which presumably provides the tissue with a high resistance to mechanical forces, particularly in respect to radial forces. The diagonal orientation of the collagen fibers is essential for the flexibility of the submucosa in allowing deformation of the intestinal wall during peristalsis. Despite the nonelastic nature of the collagen fibers, the submucosa can adapt to the various shapes of the intestinal lumen by simply changing the angles formed by these fibers. Structures of the villous microcirculation, the muscularis mucosae and of the submucous plexus are also discussed. PMID- 2194551 TI - Myristoylation of gag proteins of HIV-1 plays an important role in virus assembly. AB - The gag proteins of HIV-1 are modified by the addition of myristic acid to the amino terminal glycine residue. Site-directed mutagenesis was used to construct a mutant of HIV-1 in which this glycine residue was changed to an alanine. Upon transfection into cos-1 cells, the mutant genome directed the synthesis of the full complement of HIV-1 proteins, but p17 and p17-containing polyproteins were not myristoylated. The cells transfected with the mutant DNA did not release any virus particles and no viral cores were visible by electron microscopy. Furthermore, supernatant from these transfected cells failed to infect CEM cells. The expression and function of gp120 on the surface of cells transfected with the mutant DNA was unaffected as these cells formed syncytia comparable in both size and number to the ones obtained with wild-type DNA. PMID- 2194552 TI - Enzyme immunoassay for detection of hybrids between PCR-amplified HIV-1 DNA and a RNA probe: PCR-EIA. AB - An enzyme immunoassay was developed to detect human immunodeficiency virus type 1 (HIV-1) DNA amplified by polymerase chain reaction (PCR-EIA). A set of primers (outer set) was used in PCR to amplify a segment of the HIV-1 gag gene from peripheral blood mononuclear cells. Hybrids between the amplified DNA and a RNA probe were measured in a microtiter plate immunoassay using a beta-D galactosidase-conjugated monoclonal antibody to DNA-RNA hybrids and a fluorescent substrate. A second set of primers (nested set) located within the outer set was used in PCR with a known template to prepare the probe. One primer of the nested set included the T7 RNA polymerase promoter at its 5' end allowing transcription of a single-stranded RNA probe. Ten copies of HIV-1 DNA could be detected by PCR EIA (42 fluorescent units with a background of 18 fluorescent units) compared with a detection limit of 1000 copies by ethidium bromide-stained agarose gel. HIV-1 DNA was detected by PCR-EIA in peripheral blood mononuclear cells from 32 of 33 seropositive patients (range 54-810 fluorescent units), and 0 of 25 seronegative patients (range 20-40 fluorescent units) (sensitivity 97%; specificity 100%). PCR-EIA offers a practical and nonisotopic method to objectively measure PCR-amplified HIV-1 DNA and has the potential for the measurement of other microbial pathogens in human body fluids. PMID- 2194553 TI - Diet and dermatology: rotten fish, red herrings and essential fatty acids. PMID- 2194554 TI - Fats and cancer. PMID- 2194555 TI - Breast cancer screening--an alternative viewpoint. PMID- 2194556 TI - Some Plymouth worthies (Part 1). PMID- 2194557 TI - Coronaries, cholesterol and children. The 1989 Long Fox lecture. PMID- 2194558 TI - Epidemiology and transmission of infection by human immunodeficiency virus. AB - The incidence of HIV infection continues to increase in the United States especially among injection drug users and women. HIV is a retrovirus that infects selected cells in the immune system and under certain conditions replicates and forms new virus capable of infecting other host cells. The infection produces a continuum of conditions ranging from an asymptomatic carrier state through a series of mild or early diseases (ARC) to devastating immune deficiency and organ dysfunction (AIDS). The virus is transmitted via sex, blood, and from mother to fetus. Immune physiology, effects of HIV on the immune system, and tests to demonstrate the presence of the infection are included. PMID- 2194559 TI - Popliteal artery leiomyosarcoma: a case report and review of the literature. PMID- 2194560 TI - Seat belt aorta. AB - This review of 11 cases of seat-belt associated blunt abdominal aortic trauma, includes nine cases reported in the literature and two new cases. Lap-type seat belts were the cause of this injury in eight of the 11 patients (73%). Clinical presentation was acute in 73% of the cases, with symptoms of acute arterial insufficiency, or an acute abdomen or neurologic deficits. Chronic manifestations, such as, persistent abdominal pain, claudication, abdominal mass with a bruit and decreased distal pulses, presented as late as nine months after the injury occurred. The mechanism producing the injury is discussed and a classification system for the different types of abdominal aortic injuries is put forth. Circumferential intimal disruption was the most common aortic defect. The majority of these were located distal to the inferior mesenteric artery. Diagnosis involves a high degree of suspicion in a victim wearing a seat belt with neurologic deficits, signs of acute arterial insufficiency, or a pulsatile abdominal mass. The mortality rate was 18% (2/11 patients), and occurred in patients wearing lap belts. Overall outcome depends on prompt recognition followed by appropriate surgical intervention. PMID- 2194561 TI - Targeting of cloned firefly luciferase to yeast mitochondria. AB - The firefly luciferase gene (luc) was fused to a 5' fragment of the 70-kDa protein gene (70K) from yeast. The fragment codes for the N-terminal putative signal sequence which targets and anchors the 70-kDa protein to the cytoplasmic side of the outer membrane in mitochondria. Two versions of the fusion gene, 70K[232]::luc and 70K[93]::luc (containing 292 and 93 5' codons from 70K, respectively), were constructed in a bacterial expression plasmid. Both the genes were expressed in Escherichia coli, and in both cases, bioluminescence activity was associated with the expression. The 70K[93]::luc gene was transferred to a yeast-bacteria shuttle vector used to transform Saccharomyces cerevisiae cells. As a control, the same strain was transformed with a plasmid including the original luc. With both transformants, bioluminescence activity was detected in intact cells and crude extracts. Upon growth on a nonfermentable carbon source and fractionation, the product of the fusion gene was associated mostly with mitochondria. In the control transformant, the product of luc was more delocalized. However, a significant amount remained associated with isolated mitochondria. No such spontaneous association of purified luciferase with wild type mitochondria was observed in vitro. Trypsin treatment of mitochondria isolated from both transformed strains indicated that the fusion protein is anchored to the outer membrane and exposed to the medium while the unfused luciferase retained with the mitochondria is occluded in a compartment unaccessible to trypsin and released in the presence of detergent. The fusion protein retained the major catalytic properties of the parent firefly luciferase, as determined in solution.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2194562 TI - Slow-binding inhibition of the Escherichia coli pyruvate dehydrogenase multienzyme complex by acetylphosphinate. AB - The pyruvate analogue acetylphosphinate (CH3-CO-PO2H2) inhibits the pyruvate dehydrogenase component (E1) of the Escherichia coli pyruvate dehydrogenase multienzyme complex in a time-dependent process with biphasic reaction kinetics. The formation of an initial, rapidly reversible enzyme-inhibitor complex (EI) with an apparent Ki of 0.12 +/- 0.025 microM is followed by the conversion to a tighter complex (EI) at a maximal rate of k3 = 0.87 +/- 0.34 min-1. The inhibition is reversible (dissociation rate constant k4 = 0.038 +/- 0.002 min-1), requires the presence of the cofactors thiamin pyrophosphate and Mg2+, and is competitive with regard to pyruvate. The microscopic rate constants give a value of 5 nM for the overall dissociation constant [Ki = [E] [I]/[( EI] + [EI]) = Kik4/(k3 + k4)] compared with values of 10 and 3.5 nM obtained by steady-state methods. Thus acetylphosphinate binds by 5 orders of magnitude more tightly to pyruvate dehydrogenase than does pyruvate (Km = 0.35 mM). Acetylphosphinate also affects the pyruvate dehydrogenase complex fluorescence when excited at 290 nm in a time-dependent manner with a maximal rate constant of 0.99 min-1, suggesting a conformational change in the enzyme complex as the slow step in conversion of EI to EI (k3). All these features taken together suggest that the interaction of the pyruvate dehydrogenase with acetylphosphinate involves the formation of a thiamin pyrophosphate-acetylphosphinate adduct that resembles the normal reaction intermediate, 2-(1-carboxy-1-hydroxyethyl)thiamin pyrophosphate (alpha lactylthiamin pyrophosphate). PMID- 2194563 TI - Temperature-dependent conformational changes in the bacteriopheophytins of Rhodobacter sphaeroides reaction centers. AB - Resonance Raman (RR) spectra are reported for the photosynthetic reaction center (RC) protein from Rhodobacter sphaeroides 2.4.1. The spectra were obtained with a variety of excitation wavelengths, spanning the UV, violet, and yellow-green regions of the absorption spectrum, and at a number of temperatures ranging from 30 to 270 K. The RR data indicate that the frequencies of certain vibrational modes of the bacteriochlorin pigments in the RC shift with temperature. These shifts are reversible and do not depend on external factors such as solvent or detergent. The acetyl carbonyl bands exhibit the largest shifts with temperature. These shifts are attributed to thermal effects involving the torsional vibrations of the acetyl groups of several (or all) of the bacteriochlorins rather than to specific pigment-protein interactions. The frequency of the structure-sensitive skeletal mode near 1610 cm-1 of one of the two bacteriopheophytins (BPhs) in the RC is also sensitive to temperature. In contrast, no temperature sensitivity is observed for the analogous modes of the bacteriochlorophylls or other BPhs. Over the range 160-100 K, the skeletal mode of the BPh upshifts by approximately 4 cm 1. This upshift is attributed to a flattening of the macrocycle at low temperatures. It is suggested that the BPh active in the electron-transfer process is the pigment whose structure is temperature dependent. It is further suggested that such structural changes could be responsible in part for the temperature dependence of the electron-transfer rates in photosynthetic RCs. PMID- 2194564 TI - Macromolecular binding equilibria in the lac repressor system: studies using high pressure fluorescence spectroscopy. AB - High hydrostatic pressure coupled with fluorescence polarization has been used to investigate protein subunit interactions and protein-operator association in lac repressor labeled with a long-lived fluorescent probe. On the basis of observation of a concentration-dependent sigmoidal decrease in the dansyl fluorescence polarization, we conclude that application of high hydrostatic pressure results in dissociation of the lac repressor tetramer. The 2-fold decrease in the rotational relaxation time and the high-pressure plateau are consistent with a tetramer to dimer transition. The volume change for tetramer dissociation to dimer is -82 +/- 5 mL/mol. The dissociation constant calculated from the data taken at 4.5 degrees C is 4.3 +/- 1.3 nM. The tetramer dissociation constant increases by a factor of 3 when the temperature is raised from 4.5 to 21 degrees C. A very small effect of inducer binding on the subunit dissociation is observed at 4.5 degrees C; the Kd increases from 4.5 to 7.1 nM. At 21 degrees C, however, inducer binding stabilizes the tetramer by approximately 0.8 kcal/mol. Pressure-induced monomer formation is indicated by the curves obtained upon raising the pH to 9.2. The addition of IPTG shifts the pressure transition to only slightly higher pressures at this pH, indicating that the stabilization of the tetramer by inducer is not as marked as that observed at pH 7.1. From the decrease in the polarization of the dansyl repressor-operator complexes, we also conclude that the application of pressure results their dissociation and that the volume change is large in absolute value (approximately 200 mL/mol). The lac repressor-operator complex is more readily dissociated upon the application of pressure than the tetramer alone, indicating that operator binding destabilizes the lac repressor tetramer. PMID- 2194565 TI - Rotational dynamics of the integral membrane protein, band 3, as a probe of the membrane events associated with Plasmodium falciparum infections of human erythrocytes. AB - Time-resolved phosphorescence anisotropy was used to study the molecular organisation of band 3 in the erythrocyte membrane. Three different rotational relaxation regimes of mobile band 3 were resolved. These populations may represent different aggregation states of band 3 within the membrane, or they may result from association of band 3 with other proteins at the cytoplasmic surface. The polycation spermine decreases the apparent mobility of band 3 by a mechanism that does not involve the underlying cytoskeleton. A monoclonal antibody directed against the cytoplasmic portion of band 3 can also cause an increase in the immobile fraction of band 3 molecules. This monoclonal antibody will inhibit invasion of erythrocytes by malaria parasites. Membranes prepared from erythrocytes infected with mature stages of the malaria parasite, Plasmodium falciparum, show altered dynamic properties corresponding to a marked restriction of band 3 mobility. PMID- 2194566 TI - The structure of mutation in mammalian cells. PMID- 2194567 TI - The myb oncogene. PMID- 2194568 TI - Negative regulation of transcriptional initiation in eukaryotes. PMID- 2194569 TI - The cell biology of transforming growth factor beta. AB - The TGF beta family of polypeptide growth factors regulates a remarkable diversity of cellular functions, many of which are not directly associated with cell growth. The present review has summarized many of the recent studies that have just begun to conceptually integrate this expanding array of TGF beta functions into the context of a three-dimensional, multicellular organ or tissue, be it normal or diseased. This fascinating research strongly implicates TGF beta as a key modulator of a wide variety of important physiologic and pathophysiologic processes. PMID- 2194570 TI - Purification and characterization of osmoregulatory betaine aldehyde dehydrogenase of Escherichia coli. AB - The osmoregulatory NAD-dependent betaine aldehyde dehydrogenase (betaine aldehyde:NAD oxidoreductase, EC 1.2.1.8), of Escherichia coli, was purified to apparent homogeneity from an over-producing strain carrying the structural gene for the enzyme (betB) on the plasmid vector pBR322. Purification was achieved by ammonium sulfate fractionation of disrupted cells, followed by affinity chromatography on 5'-AMP Sepharose, gel-filtration and ion-exchange chromatography. The amino acid composition was determined. The dehydrogenase was found to be a tetramer with identical 55 kDa subunits. Both NAD and NADP could be used as cofactor for the dehydrogenase, but NAD was preferred. The dehydrogenase was highly specific for betaine aldehyde. None of the analogs tested functioned as a substrate, but several inhibited the enzyme competitively. The enzyme was not activated by salts at concentrations encountered during osmotic upshock, but it was salt tolerant, retaining 50% of maximal activity at 1.2 M K+. It is inferred that salt tolerance is an essential property for an enzyme participating in the cellular synthesis of an osmoprotectant. PMID- 2194571 TI - Cooperation of lysosomes and inner mitochondrial membrane in the degradation of carbamoyl phosphate synthetase and other proteins. AB - Carbamoyl phosphate synthetase (CPS) from rat liver is proteolitically inactivated at acid pH by broken lysosomes. Inactivation increases when lysosomes are previously incubated with inner mitochondrial membrane, although this mitochondrial fraction does not inactivate CPS 'per se'. The increased degradation is due to membrane factor(s), most probably mitochondrial proteinase(s), solubilized by lysosomal matrix proteinases, after incubation of the inner mitochondrial membrane fraction with broken lysosomes. This (these ) factor(s) degrade(s) CPS and other proteins in the absence of lysosomal proteinases or when these are inhibited by leupeptin, chymostatin and pepstatin. We have also tested the possible regulation of this degradation and found that ATP and, particularly, acetyl glutamate accelerate the degradation of CPS by the factor(s) liberated from the inner mitochondrial membrane. PMID- 2194572 TI - Immunological detection of NADH-specific enoyl-ACP reductase from rape seed (Brassica napus)--induction, relationship of alpha and beta polypeptides, mRNA translation and interaction with ACP. AB - An antibody has been raised against rape seed enoyl-ACP reductase. This recognizes both the alpha and beta polypeptides of the enzyme. Immunoblotting of fresh seed demonstrates that beta is not present in seed material, and that it is produced by proteolysis during isolation. It is thus deduced that rape seed enoyl reductase is an alpha 4 homotetramer. Leaf material from both rape and Arabidopsis have an enoyl reductase with a similar electrophoretic mobility to the rape seed enzyme when analyzed on SDS-PAGE. Quantitative immunoassay has demonstrated that the enzyme continually increases during lipid deposition, indicating that an increase in this enzyme is required to sustain high levels of lipid biosynthesis. In vitro translation experiments show that the enzyme is nuclear coded and synthesized as a precursor form. Immunogold electron microscopy has demonstrated that enoyl reductase is located in plastids. It is shown that ACP-Sepharose may be used as a matrix in the purification of enoyl-ACP reductase. PMID- 2194573 TI - Myristic acid is incorporated into the two acylatable domains of the functional glycoprotein CD9 in ester, but not in amide bonds. AB - CD9 is a signal-initiating glycoprotein of uncertain membrane insertion which contains more than one locus of acylation and is distinguished by being the major acylatable platelet protein. The N-terminus of CD9 is blocked to Edman degradation. We investigated whether [3H]myristic acid could be incorporated into CD9, whether that incorporation occurred via an amide linkage, and whether myristate and palmitate were differentially incorporated into the two domains. Pulse-labeling studies, performed on the human osteogenic sarcoma cell line SKOSC which expresses 22 and 24 kDa variants of CD9 demonstrated that the respective precursors of 20.5 and 23 kDa were not radiolabeled by either [3H]myristic acid or [3H]palmitic acid, but that both fatty acids could be ligated to CD9 during the later stages of protein maturation. The failure to incorporate myristic acid cotranslationally suggest that CD9 does not contain amino-terminal amide-bonded myristic acid. Incorporation of radiolabel from both fatty acids proceeded very rapidly and could be visualized after a 10 s pulse. Although myristic acid was partially metabolized into palmitic acid, incorporation of authentic [3H]myristate into CD9 could be demonstrated. The myristic acid bonds were shown to be as sensitive to hydroxylamine treatment as those linking palmitate. Both fatty acids were also incorporated into CD9 in hydroxylamine-sensitive bonds in the presence of cycloheximide, reaching 30-40% of the levels in untreated controls. The sensitivity of myristate ligands to hydroxylamine demonstrates that this fatty acid is not linked via amide, but rather via ester bonds. The sensitivity of [3H]myristate and [3H]palmitate bonds to 2-mercaptoethanol further suggests that either fatty acid is linked via thioester rather than hydroxyester bonds to each domain on CD9. Limited proteolysis analysis with Staphylococcus aureus V8 proteinase of CD9, labeled in the absence or presence of cycloheximide, showed that [3H]myristic acid and [3H]palmitic acid labeled identical peptides, and to the same extent, suggesting that myristate is an alternative substrate for the transacylase(s) involved. PMID- 2194574 TI - Further characterization of the diacylglycerol-phosphatidylethanolamine exchange reaction catalyzed by cell-free extracts of Escherichia coli. AB - The conditions for phosphatidylethanolamine (PE)-diacylglycerol (DAG) exchange catalysed by cell-free extracts of Escherichia coli were studied using 14C- or 3H analogues of both these lipids. The reaction, examined with either labelled PE or labelled DAG, occurred without co-factor addition and was inhibited by Ca2+ and Mg2+. Detergents such as Triton X-100 greatly enhanced the activity; however, the optimal concentration of this agent depended on the lipid substrate concentration. The exchange-catalysing enzyme involved in these extracts appeared to be very specific for DAG and PE, since no other labelled phospholipid or acylglycerol derivative formed radioactive product under the assay conditions tested. Again, endogenous [3H]PE present in the enzyme source, but no other endogenous lipid, was converted to labelled DAG in the presence of added 1,2 dioleoyl-sn-glycerol. The Vmax value for the conversion of labelled PE to DAG was very similar to the Vmax value found for the conversion of labelled DAG to PE as would be expected in the case of an exchange reaction being responsible for both conversions. However, the Km value for PE was appreciably larger than that for DAG. The enzyme involved, displayed a broad acyl chain specificity as could be judged from: (1) the ability of various species of DAG and PE to stimulate the exchange; (2) the suitability of lipid substrates prepared from widely different biological sources; and (3) the interchange of acyl groups that occurred between dimyristoyl PE and dilauroylglycerol. As would be expected for an exchange reaction, the incorporation of lauroyl groups into PE occurred without an increase in the total fatty acid content of this phospholipid. The results of the present study confirm and further characterize the PE-DAG exchange reaction of E. coli. PMID- 2194575 TI - Thrombin-induced expression of the KC gene in cultured aortic endothelial cells. Involvement of proteolytic activity and protein kinase C. AB - The KC gene, first identified in platelet-derived growth factor-stimulated BALB/c 3T3 cells, shares structural similarities with a new family of genes that code for secreted cytokines which appear to be involved in wound healing and inflammation. Thrombin is a coagulation system proteinase likely to be present in vivo at sites of tissue injury. This enzyme is known to stimulate multiple responses in cultured endothelial cells (EC), including the production of eicosanoids, the expression of growth factor genes and the adhesion of leukocytes. The present experiments were designed to examine the effect of thrombin on KC mRNA expression in EC and to explore the molecular mechanisms involved. Thrombin caused a marked concentration-dependent increase in the steady state level of KC mRNA in confluent porcine aortic EC. The level of KC mRNA reached a peak 2 h after thrombin treatment and returned to near control levels by 8 h. Thrombin that was pretreated with phenylmethylsulfonyl fluoride (PMSF) to block proteolytic activity did not stimulate KC gene expression. Trypsin (2 micrograms/ml) but not PSMF-trypsin also caused a substantial increase in the level of KC mRNA. We postulated a role for protein kinase C in thrombin-induced KC gene expression since previous work had demonstrated a similar EC response to phorbol esters. This hypothesis was further supported by the finding that thrombin-induced KC expression was suppressed by the C kinase inhibitor 1-(5 isoquinolinesulfonyl)-2-methylpiperazine, but not by its structural analogue. The results of the present study demonstrate that thrombin augments KC mRNA expression by vascular EC in a process that requires intact proteinase activity. The activation of protein kinase C may be a necessary component of the intracellular signalling pathway involved in this response. PMID- 2194576 TI - Characterization of a cDNA clone encoding the complete amino acid sequence of cotton isocitrate lyase. AB - A cDNA clone encoding the glyoxysomal enzyme isocitrate lyase (ICL) (EC 4.1.3.1) was isolated from a library prepared from cotton (Gossypium hirsutum L.) cotyledon poly(A)+ RNA. The clone is 1893 basepairs (bp) in length and contains a 1728 bp open reading frame encoding a polypeptide of 576 residues (Mr = 64,741). The deduced amino acid sequence of cotton ICL is 85.2%, 90.3% and 41.1% identical to ICL from rapeseed, castor bean and E. coli, respectively. Cotton ICL has a C terminal tripeptide of A-R-M which is a putative trafficking signal for peroxisome (glyoxysome) proteins. PMID- 2194577 TI - Nucleotide sequences of the meta-cleavage pathway enzymes 2-hydroxymuconic semialdehyde dehydrogenase and 2-hydroxymuconic semialdehyde hydrolase from Pseudomonas CF600. AB - The nucleotide sequence of a 2493 base pair (bp) region, spanning the coding regions for the meta-cleavage pathway enzymes 2-hydroxymuconic semialdehyde dehydrogenase (HMSD) and 2-hydroxymuconic semialdehyde hydrolase (HMSH), was determined. The deduced protein sequence for HMSD is 486 amino acid residues long with an Mr of 51,682. HMSD has homology with a number of aldehyde dehydrogenases from various eukaryotic sources. The deduced protein sequence for HMSH is 283 amino acids long with an Mr of 30,965. The amino acid composition of this enzyme is similar to that of isofunctional enzymes from toluene and m-cresol catabolic pathways. PMID- 2194578 TI - Sequence-specific 1H-NMR assignments for the aromatic region of several biologically active, monomeric insulins including native human insulin. AB - The aromatic region of the 1H-FT-NMR spectrum of the biologically fully-potent, monomeric human insulin mutant, B9 Ser----Asp, B27 Thr----Glu has been investigated in D2O. At 1 to 5 mM concentrations, this mutant insulin is monomeric above pH 7.5. Coupling and amino acid classification of all aromatic signals is established via a combination of homonuclear one- and two-dimensional methods, including COSY, multiple quantum filters, selective spin decoupling and pH titrations. By comparisons with other insulin mutants and with chemically modified native insulins, all resonances in the aromatic region are given sequence-specific assignments without any reliance on the various crystal structures reported for insulin. These comparisons also give the sequence specific assignments of most of the aromatic resonances of the mutant insulins B16 Tyr----Glu, B27 Thr----Glu and B25 Phe----Asp and the chemically modified species des-(B23-B30) insulin and monoiodo-Tyr A14 insulin. Chemical dispersion of the assigned resonances, ring current perturbations and comparisons at high pH have made possible the assignment of the aromatic resonances of human insulin, and these studies indicate that the major structural features of the human insulin monomer (including those critical to biological function) are also present in the monomeric mutant. PMID- 2194579 TI - Planning and monitoring of equivalence studies. AB - Demonstrating therapeutic equivalence of two treatments is the goal of many clinical trials. For instance, when the toxicity of an effective standard treatment is of concern, much effort is devoted to developing new therapies that would be both as effective and less toxic. In this paper we review the special characteristics of these trials and describe sequential monitoring of equivalence studies using repeated confidence intervals. We show how sequential monitoring may be of particular value in this setting and critically discuss the choice of some important design parameters. We also provide tables for use when planning a sequential equivalence trial. PMID- 2194580 TI - [A mathematical model of the processes of mitochondrial death and reproduction during body irradiation]. AB - A method of construction of mathematical model of processes of death and reproduction of mitochondria based on morphometric measurements is proposed. Using the model the time of mitochondria death and reproduction during ionized irradiation of the organism is identified. PMID- 2194581 TI - [Thymus involution and recovery in mice after the administration of lipopolysaccharide]. AB - The single injection of 50 micrograms LPS induces polyclonal immune response in the spleen of (CBA x C57B1/6) F1 mice. It is accompanied by the thymic involution and depletion of blasts and mitoses, as showed morphometric analysis. Vinblastin does not induce: accumulation of the mitoses during the first and second days after LPS injection. The regeneration of the thymus begins already from the second day with increasing of blast cells, reaching a maximum at the 3rd day. The mitosis wave retards two days and achieves peak at the 5th day. The regeneration of the thymus finishes at the 13th day aster LPS injection, but the blast number is higher, than the control level. PMID- 2194582 TI - [An immunochemical study of M-HeLa cells as producers of human placental alkaline phosphatase]. AB - While analyzing M-HeLa cells by IFA technique secretory and membrane-bound forms of human placental alkaline phosphatase (HPAP) were detected. Activity of secretory HPAP increased if cell density and incubation time were increased too. After short influence of heat shock (15 min at 42 degrees C) activity of secretory HPAP increased for 45% and intracellular HPAP 3 for 37%. It is proposed that HPAP take part in organization of first response to heat shock and support cellular thermotolerance. PMID- 2194583 TI - [The paraneoplastic phenotype of human gastric glands studied using the carcinoembryonic antigen-specific lectin crustacin]. AB - The expression of CEA was studied with the help of rabbit antibody and CEA specific lectin-krustacin in pepsinogen positive gastric glands near carcinomas and in gastric mucosa with intestinal metaplasia and dysplasia of the epithelium without neoplasia. CEA-krustacin was revealed in 20 out of 41 cases and CEA antibody in 2 out of 41 cases of gastric glands in mucosa near carcinomas. The results of investigation discover the development in the gastric glands near carcinoma subcellular components. Paraneoplastic phenomenon was found in the majority of the cases. PMID- 2194584 TI - [Structural changes in the DNA of the blood nucleotides and the development of late sequelae in irradiated rats]. AB - Fluorescent analysis of structural changes of nucleotide in the blood associated with AT fragments has been studied in rats, gamma-irradiated with doses of 2 and 4 Gy. It was demonstrated that the haematological, gerontological and cancerogenic late consequences were preceded by the structural genomic disturbances determined by 30 day after irradiation. PMID- 2194586 TI - Direct sequence analysis of the 14q+ and 18q- chromosome junctions in follicular lymphoma. AB - Although the t(14;18) chromosome translocation has been demonstrated to be a highly consistent feature of follicular lymphomas, the underlying mechanism generating this fusion has remained uncertain. To examine this question further, a polymerase chain reaction strategy has been devised to permit the amplification and direct sequencing of the resultant 14q+ and 18q- reciprocal junctions. Direct sequence analysis of amplified 14q+ junctions established that 7 of 11 tumors contained a bcl-2 (mbr) sequence fused to an immunoglobulin JH region (five were J6 and two were J5). One of these junctions had an unusual configuration with the bcl-2 and JH sequences separated by a recognizable DH region. This finding suggests that at least some of the junctional sequences, previously thought of as N insertions, may be fragments of unrecognized DH regions. It was also possible to amplify and sequence 18q- junctions using a primer based on the DH recombination signal sequences. Several 18q- junctions were shown to consist of DH/bcl-2 (either mbr or mcr) fusions. In two tumors the 14q+ and 18q- junctions were fully sequenced, and it was demonstrated that the bcl-2 sequence was conserved during mbr and mcr translocations. This contrasts with previous analyses that demonstrated either loss or duplication of several bases at the breakpoints in the bcl-2 gene. PMID- 2194585 TI - Surface-dependent reactions of the vitamin K-dependent enzyme complexes. AB - During the past 20 years contributions from many laboratories have led to the development of isolation procedures, delineation of primary structures, and more recently, to the expression of recombinant proteins associated with the coagulation cascade. In general, studies of coagulation proteins under defined conditions have demonstrated the prescience of Davie and Ratnoff and MacFarlane in their proposals of the coagulation cascade. The more recent discovery of thrombomodulin by Esmon et al has led to the identification and characterization of components of the vitamin K-dependent anticoagulant pathway. In this review we have attempted to analyze and compare the functional properties of each of the vitamin K-dependent enzyme complexes associated with the procoagulant and anticoagulant phases of blood clotting. Although dissimilarities exist, the vitamin K-dependent complexes have analogous requirements and appear to function with a common general mode of organization. Membrane-bound cofactors serve as anchoring sites for the appropriate membrane-binding enzymes. This process localizes the complex on the membrane surface and increases the catalytic efficiency for substrate utilization. Complex formation provides extraordinary improvements in the catalytic efficiency for the complexes as compared with their soluble enzyme components. Membrane-bound complexes provide a mechanism that can be regulated at a site by membrane presentation, zymogen activation, and cofactor activation or presentation. The kinetic constants obtained for the various coagulation reactions determined in vitro provide some insights into how these pathways may function in vivo. The catalytic efficiency (kcat/Km) for factor X activation by factor VIIIa/factor IXa is far in excess of the catalytic efficiency of activation of factor X by tissue factor/factor VIIa (Table 3). This may provide a rational interpretation for the observation that patients with hemophilia A and B bleed even though they appear to have an alternative pathway to factor X activation. In addition, tissue factor is not ordinarily presented by the vascular tissue that has direct access to blood. However, it appears that extravascular constitutive tissue factor is available once the blood vessel becomes disrupted. The efforts to identify the initiating reactions of the blood coagulation process have not been unambiguously successful. We conclude that factor VII is most likely a zymogen, just as are the other proenzymes of the blood clotting process. In addition, it is difficult to rationalize the importance of the intrinsic pathway of coagulation involving factor XII, prekallikrein, and high molecular weight kininogen since the congenital absence of any one of these factors does not result in abnormal bleeding.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2194588 TI - Association between clonogenic cell growth and clinical risk group in B-cell chronic lymphocytic leukemia. AB - Chronic lymphocytic leukemia of B-cell origin (B-CLL) is a disease with a variable clinical course, despite the fact that the neoplastic cells in this disorder are homogeneous with respect to morphology, immunophenotype, and cell cycle stage. To further investigate the heterogeneity observed in the clinical behavior of B-CLL, we determined the phenotype and growth requirements of clonogenic cells from 28 patients with B-CLL from low-, intermediate-, and high risk groups as defined by the Rai staging system. Using methyl-cellulose as a semi-solid media with feeder cells and/or growth factors, colonies were observed with one or more of the culture conditions tested in 25 of 28 CLLs. Phenotypic analysis of colonies demonstrated that the clonogenic cells uniformly expressed la, CD19, CD20, CD5, and the identical light chain as the original CLL cell cultured. However, heterogeneity was observed in clonogenic B-CLL cell growth among the three different CLL risk groups. Clonogenic cells from patients with low-risk CLL required either irradiated unstimulated T cells, with or without conditioned media (CM) or irradiated activated T cells alone for colony formation. Both the number of colonies (227 +/- 15) as well as the number of cells per colony (220 +/- 82) were large, with a mean cloning efficiency of 0.39%. In contrast, clonogenic cells from patients with intermediate- and high risk CLL required the combination of both irradiated activated T cells and CM. As compared with the low-risk CLLs, both the number and size of the colonies formed by the intermediate- (74 +/- 17, 70 +/- 39) and high- (83 +/- 28, 40 +/- 14) risk groups were significantly lower (P less than .0001). Similarly, the mean cloning efficiency was significantly reduced to 0.15% and 0.14%, respectively. None of the recombinant cytokines (interleukin 1 [IL-1] to IL-7, tumor necrosis factor, alpha and gamma-interferon, B-cell growth factor, and granulocyte macrophage colony-stimulating factor) alone or in combination with each other could entirely replace the stimulatory effect of the activated T cells. These data suggest that clinical progression of B-CLL is associated with a loss of clonogenic potential in the circulating pool of neoplastic cells, which require as yet undefined factors provided by activated T cells and CM. PMID- 2194587 TI - Immunologic characterization of the tumor-specific bcr-abl junction in Philadelphia chromosome-positive acute lymphoblastic leukemia. AB - Philadelphia (Ph')-positive acute lymphoblastic leukemia (ALL) is highly associated with two forms of chimeric bcr-abl proteins: P190bcr-abl and P210bcr abl. Whereas P210bcr-abl also occurs in chronic myeloid leukemia, P190bcr-abl is uniquely expressed in Ph'-positive ALL. As a consequence, P190bcr-abl is preeminently a tumor-specific marker in leukemic cells of ALL patients. Because P190bcr-abl is composed of the normal bcr and abl proteins, the major part of the P190bcr-abl molecule comprises nontumor-specific determinants. The joining region between bcr and abl, newly generated during the Ph' translocation, is exclusively a tumor-specific epitope on the P190bcr-abl molecule. Therefore, only antibodies against the bcr-abl joining region will detect the tumor-specificity of P190bcr abl. In this study a polyclonal antiserum, termed BP-ALL, was raised against a synthetic peptide corresponding to the bcr-abl junction in P190bcr-abl. The reactivity of BP-ALL with native P190bcr-abl derived from a Ph'-positive ALL cell line (TOM-1) was tested using immunoprecipitation analysis. BP-ALL reacted highly specifically with P190bcr-abl but not with P210bcr-abl isolated from chronic myeloid leukemia cell lines. Peptide inhibition studies further confirmed the fine specificity of BP-ALL. Our data indicate that the tumor-specific bcr-abl junction domain is exposed in an antigenic fashion on the P190bcr-abl molecule. PMID- 2194589 TI - Regulation and lectin activity of the human neutrophil peripheral lymph node homing receptor. AB - We characterize the nature and regulation of a human neutrophil cell surface antigen recognized by monoclonal antibodies (the DREG series) against a human lymphocyte peripheral lymph node homing receptor. Human neutrophils express high levels of the DREG antigen, whose expression is downregulated after treatment with phorbol myristate acetate, or the chemotactic factors C5a and FMLP. Interestingly, C5a treatment also downregulated the monocyte DREG antigen, but had no effect on expression of the lymphocyte molecule. Within 3 minutes after treatment with C5a, greater than 80% of neutrophil DREG antigen expression is lost, and essentially the molecule is completely removed from the cell surface by 5 minutes. The human neutrophil DREG antigen is 10 Kd larger than the lymphocyte molecule. These features are similar to those of the mouse neutrophil MEL-14 antigen (murine peripheral lymph node homing receptor). The mannose-6-phosphate rich phosphomannan (PPME) binds human lymphocytes via the DREG antigen. PPME also binds neutrophils, but little difference in binding is seen between unactivated and activated cells. We show that PPME binding to unactivated neutrophils is mediated primarily by a cation- and DREG antigen-dependent mechanism, whereas activated neutrophil-PPME binding is DREG antigen- and cation-independent, and may be due to the translocation of lysosomal mannose-6-phosphate receptors to the cell surface. The DREG antibodies offer powerful tools for analyzing the role of homing receptors in human neutrophil-endothelial cell interactions, and also may prove valuable in the clinical assessment of neutrophil activation. PMID- 2194590 TI - Value of day 100 screening studies for predicting the development of chronic graft-versus-host disease after allogeneic bone marrow transplantation. AB - We prospectively evaluated 169 patients with a number of screening studies performed between 71 to 121 days after allogeneic marrow transplantation to detect the development of chronic graft-versus-host disease (GVHD). Group 1 patients (n = 78) were asymptomatic and had normal physical examinations at the time of screening and, with a minimum of 8 years follow-up, have not developed chronic GVHD. Group 2 patients (n = 38) had signs and symptoms of chronic GVHD at time of testing. Group 3 patients (n = 53) were similar to those in group 1 in having no clinically evident GVHD at the time of testing, but later developed clinical chronic GVHD. Using time to an event analysis, we compared patients in groups 1 and 3 to determine which of 17 clinical and laboratory factors evaluated at screening accurately predicted the development of subsequent chronic GVHD. Multivariate analyses showed several factors to have independent predictive value. In the first model, results of oral biopsies were excluded since these were done only in one half of the patients. Predictive factors in this analysis included: (1) histologic findings of GVHD on skin biopsy, relative risk 3.23 (95% confidence interval 1.75 to 5.94), P = .0002; and (2) history of grade II through IV acute GVHD, relative risk 3.12 (95% confidence interval 1.72 to 5.64), P = .0002. When oral biopsy results were included in the second model, independent risk factors included: (1) histologic findings of GVHD on skin biopsy, relative risk 5.96 (95% confidence interval 1.95 to 18.19), P = .0017; and (2) low numbers of immunoglobulin A (IgA)-bearing plasma cells detected by direct immunofluorescence in salivary gland areas on oral biopsy, relative risk 11.53 (95% confidence interval 2.51 to 52.03), P = .0017. Our study demonstrates the value of day 100 screening studies for predicting subsequent development of clinical chronic GVHD. PMID- 2194591 TI - T-cell-depleted autologous bone marrow transplantation therapy: analysis of immune deficiency and late complications. AB - Fourteen patients with T-cell-derived leukemia and lymphoma underwent high-dose chemoradiotherapy and anti-T-cell monoclonal antibody-treated autologous bone marrow transplantation (ABMT). All patients were either in sensitive relapse or had adverse prognostic features, and five patients had a history of bone marrow involvement with disease. Patients received a median of 2 (1 to 3) prior chemotherapy regimens; 10 patients received local radiotherapy. After high-dose ablative therapy, greater than 500/mm3 granulocytes and greater than 20,000 untransfused platelets/mm3 were noted at a median of 23 (13 to 48) and 26 (15 to 43) days post-ABMT, respectively. Natural killer (NK) cells, T cells (predominantly T8+), and monocytes were noted within the first 1 to 2 months post AMBT, as seen in other series. Disease-free survival was a median of 10.1 months, 5.9 months for patients with T acute lymphoblastic leukemia or lymphoblastic lymphoma and 25.6 months for patients with T non-Hodgkin's lymphoma (NHL). Toxicities were common and severe. Thirty-six percent of patients developed bacteremias early post-BMT. Late complications included a skin rash consistent with graft versus host disease; infections with Herpes zoster, hepatitis, and Pneumocystis carinii; and the development of Epstein-Barr virus associated lymphoproliferative syndrome. Our findings suggest that patients who have undergone T-depleted ABMT have a profound immunodeficiency not reflected in the phenotypic reconstitution of the T and NK cells. Characterization of the functional deficiency may facilitate the development of methods to reduce the long-term toxicity of AMBT in these patients. PMID- 2194592 TI - Use of recombinant human granulocyte-macrophage colony-stimulating factor in graft failure after bone marrow transplantation. AB - The effect of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was evaluated in 37 patients with marrow graft failure after allogeneic (n = 15), autologous (n = 21), or syngeneic (n = 1) bone marrow transplantation. rhGM-CSF was administered by 2-hour infusion at doses between 60 and 1,000 micrograms/m2/d for 14 or 21 days. At doses of less than 500 micrograms/m2, rhGM-CSF was well-tolerated and did not exacerbate graft-versus host disease in allogeneic transplant recipients. No patient with myelogenous leukemia relapsed while receiving rhGM-CSF. Twenty-one patients reached an absolute neutrophil count (ANC) greater than or equal to 0.5 x 10(9)/L within 2 weeks of starting therapy while 16 did not. None of seven patients who received chemically purged autologous marrow grafts responded to rhGM-CSF. The survival rates of GM-CSF-treated patients were significantly better than those of a historical control group. PMID- 2194593 TI - Three case reports of the metabolic and electroencephalographic changes during advanced Buddhist meditation techniques. AB - To examine the extent to which advanced meditative practices might alter body metabolism and the electroencephalogram (EEG), we investigated three Tibetan Buddhist monks living in the Rumtek monastery in Sikkim, India. In a study carried out in February 1988, we found that during the practice of several different meditative practices, resting metabolism (VO2) could be both raised (up to 61%) and lowered (down to 64%). The reduction from rest is the largest ever reported. On the EEG, marked asymmetry in alpha and beta activity between the hemispheres and increased beta activity were present. From these three case reports, we conclude that advanced meditative practices may yield different alterations in metabolism (there are also forms of meditation that increase metabolism) and that the decreases in metabolism can be striking. PMID- 2194594 TI - Acquired abnormalities of polymorphonuclear neutrophil function. AB - Normal polymorphonuclear neutrophils (PMN) in the circulation are resting cells expressing small numbers of low affinity receptors. During inflammation they are upregulated to increase expression of high affinity receptors and discharge both primary and secondary granules. This is reflected by a pattern of changes which can be detected in PMN from the circulation of patients with infection, trauma or burns. Different patterns of abnormality occur in patients with systemic disease and increased risk of infection such as diabetes and renal failure. Functional defects also occur in PMN from patients with acquired blood disorders. It is likely that PMN contribute to tissue damage in inflammatory and vascular diseases so that drugs which modulate PMN function will be of future therapeutic benefit. PMID- 2194595 TI - Histological classification of the non-Hodgkin's lymphoma. AB - The non-Hodgkin's lymphomas (NHL) are a diverse group of neoplasms which show subtle histological differences. This has led to difficulties in formulating reproducible classifications of NHL that are both histologically and clinically relevant. In this review we discuss some of the historical aspects of NHL classification leading up to the principal classifications in current use. In comparing these we put forward reasons why we regard the updated Kiel classification as that which is the most soundly based in clinical, histological and biological terms. The Kiel classification, unlike its competitors, lends itself to further updating as new clinicopathological entities become established, without loss of its essentially sound foundations. Thus the classification of T-cell lymphomas can only be regarded as provisional and certain extranodal lymphomas, which are clear clinicopathological entities, await classification. The biological foundation of the Kiel classification should allow further updating to incorporate these entities and the tighter definitions of categories of NHL that will surely result from the application of cytogenetics, molecular biology and studies of lymphocyte homing mechanisms. PMID- 2194596 TI - Bone marrow transplantation for genetic disorders. AB - In 1967, a congenital disorder, severe combined immune deficiency disease, (SCID), was the first condition to be successfully corrected by bone marrow transplantation (BMT) from a histocompatible matched sibling donor. Since then the number of inherited disorders in which BMT has been used has been greatly extended. In preface, it should be stressed that BMT represents only one aspect of the management of genetic disorders which includes first and foremost detection and prevention by antenatal screening. Enzyme replacement treatment and the development of genetic engineering techniques to correct the underlying fault are being actively explored. However, reliable screening programmes are only feasible in a minority of disorders, of which thalassaemia is an example. Enzyme replacement treatment has been largely unsuccessful, and despite considerable advances in the understanding of gene regulation, at present BMT represents the only practice capable of correcting genetic disorders and improving the quality of life of affected individuals. PMID- 2194597 TI - Bone marrow transplantation utilizing HLA-matched unrelated marrow donors. PMID- 2194598 TI - Haemochromatosis. PMID- 2194600 TI - Pathophysiology of aplastic anaemia. AB - It is the conventional opinion that acquired aplastic anaemia is a heterogenous disease including basically different conditions, such as idiopathic or virus induced pancytopenia, toxic-allergic marrow damage or autoimmunity. Here, an alternative concept is proposed, according to which aplastic anaemia is one disease, but multifactorial in all patients, apparent differences being due to the relative prevalence of one or the other pathophysiological component in individual patients. Bone marrow from patients in the severe phase of aplastic anaemia does not grow in culture and is therefore not suitable for experimentation. Alternatively, bone marrow from patients who have resumed some degree of autologous bone marrow function, but still have residual signs of the disease after non-invasive therapy, offers the possibility to study pathophysiological mechanisms in vitro. The majority of experiments presented in this chapter have been done in such patients, assuming that their status of disease in some way reflects the original, more serious pretreatment condition. Three major pathophysiological components will be discussed, and it will be proposed how these factors act in concert to cause or aggravate aplasia. PMID- 2194599 TI - The porphyrias. AB - The porphyrias are a group of metabolic disorders arising from defects in the haem biosynthetic pathway. Most forms are inherited as Mendelian autosomal dominant characters, but some are recessive and others acquired. There is a linked group of diseases, which are not porphyrias, but have in common alterations of haem biosynthesis. The haem biosynthetic pathway is now well understood and the molecular biology of its function and dysfunction in the porphyrias is currently an area of major investigation. The acute porphyrias are of most importance since attacks of these may be life-threatening. A variety of factors may precipitate these attacks including various drugs, alcohol, strict dieting or fasting and hormonal fluctuations. The non-acute porphyrias are largely dermatological conditions, which present clinically as cutaneous photosensitivity. The dermatological changes are brought about by the photosensitizing properties of circulating porphyrins. On the basis of this photoactivity, porphyrins are now being used, therapeutically, in the treatment of cancer. PMID- 2194601 TI - Recent advances in bone cell biology: interactions of vitamin D with other local and systemic factors. PMID- 2194602 TI - The pathogenesis of osteoporosis. AB - Changes in the calciotropic hormones with age contribute significantly to the pathogenesis of osteoporosis. In both postmenopausal (Type I) and senile osteoporosis (Type II) it is common to find reduced levels of serum 1,25 dihydroxyvitamin D and malabsorption of calcium. In Type I patients a reduced level of serum parathyroid hormone causes a real decrease in serum 1,25 dihydroxyvitamin D production and malabsorption of calcium, whereas in Type II patients the decline in 1 alpha-hydroxylase activity in the kidney causes a decline in serum 1,25-dihydroxyvitamin D which leads to malabsorption of calcium and secondary hyperparathyroidism. In the final analysis both pathways lead to bone loss. In some Type II patients there may be a decline also in the function or number of the vitamin D-binding receptors in the gut. Treatment of patients with vitamin D analogues, however, normalizes calcium absorption and improves calcium balance. The improvement in calcium balance reduces bone resorption and prevents further bone loss; in addition recent studies have shown that therapy with vitamin D analogues leads to a reduction in fracture incidence. PMID- 2194603 TI - Cochlear and cerebrospinal fluid pressure: their inter-relationship and control mechanisms. AB - The patency of the cochlear aqueduct is a key factor in intra-cochlear hydromechanics. If patent, the cerebrospinal fluid (CSF) provides the reference pressure for the perilymph and also to a large extent the endolymph, since Reissner's membrane can only withstand a relatively small pressure differential. The aqueduct often becomes sealed as a natural process of ageing. In this instance the reference pressure is from a source, its position unknown, within the boundaries of the cochlea itself. Relatively large and rapid changes in the cerebrospinal fluid pressure may result from everyday events such as coughing (ca. 175 mm saline) and sneezing (ca. 250 mm saline). The resistive nature of the cochlear aqueduct and the mechanical compliance of the cochlear windows are probably important factors in limiting the amount of stress, and therefore possible damage, which may occur to the cochlea and cochlear windows for a given pressure change within the CSF system. A narrow aqueduct and compliant cochlear windows reduce the risk of structural damage. In practice, this should mean that the risk of structural damage will be increased by any process which reduces the compliance of one or both of the cochlear windows, for example, extremes of middle ear pressure perhaps brought about by Eustachian tube dysfunction or rapid barometric pressure changes. Techniques are now available which provide non invasive indirect measures of perilymphatic pressure and CSF-perilymphatic pressure transfer. The tympanic membrane displacement measurement technique has been used to provide reliable measures of perilymphatic pressure and CSF perilymphatic pressure transfer on an individual subject basis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2194604 TI - Towards a psychology of caring. AB - An increasing awareness of the chronicity of many conditions, and reservations about the appropriateness of 'treatment' models of intervention, together encourage a positive and careful psychological examination of caring. A psychology of caring must be relevant to care by families in domestic settings as well as to more specialized and professionally staffed settings. The relationship between explicit and implicit philosophies of caring, the goals and objectives of caring, the care practices themselves, and the emotions and feeling associated with care, need to be carefully examined. As applied psychologists, there are many detailed aspects of care we could examine, including the nature of need, vigilance, risk taking, the elicitation of care, identifying the motivation of potential carers, and care evaluation. Much of the literature on caring is derived from organizational and sociological perspectives: there is room for, and a need for, a specifically psychological perspective as well. PMID- 2194605 TI - An overview of anxiety disorders. AB - Anxiety disorders are more prevalent than any other mental health problem in the United States. Afflicted persons are often untreated or are treated only by a primary care physician without psychiatric consultation. However, based on current knowledge of the biological and psychological factors involved in these disorders, psychiatry has defined effective treatment that integrates education, psychotherapy, and psychopharmacology. After reviewing current research on possible mechanisms of anxiety, the authors discuss therapeutic interventions and recommend ways to choose appropriate treatment modalities for anxiety-disordered patients. PMID- 2194606 TI - Through the storm: psychoanalytic theory in the psychotherapy of the anxiety disorders. AB - Anxiety is one of the most ubiquitous problems facing human beings. The author summarizes the views of the major psychodynamic theorists who have contributed to a psychoanalytic understanding of anxiety: Freud's toxic and signal theories; the interpersonal schools of Harry Stack Sullivan, Karen Horney, and Frieda Fromm Reichmann; the object relations theorists; and the self-psychological perspective of Heinz Kohut. The author then describes how each of these schools provides a different way to appreciate and work with anxiety. She emphasizes the containing and soothing functions of therapy, which have their roots in several of the theories. PMID- 2194607 TI - Mitral valve prolapse and panic disorder. AB - The literature and clinical experience suggest a higher-than-normal incidence of mitral valve prolapse in patients with panic disorder, although the relationship between these two conditions is currently a matter of speculation. Patients with panic disorder are likely to first consult their family practitioner or internist, who may then refer them to a psychiatrist. Hence psychiatrists should be familiar with the signs, symptoms, and management of mitral valve prolapse. The authors describe mitral valve prolapse, panic disorder, and their association, then suggest a strategy for evaluation and treatment of these conditions. PMID- 2194608 TI - Hypnosis in the treatment of anxiety. AB - Hypnotherapy and training in self-hypnosis can help persons achieve remarkable success in alleviating anxiety, not only in anxiety disorders, but also in any problem involving anxiety. The author describes the role of hypnosis in the treatment of several disorders and provides clinical examples illustrating treatment of generalized anxiety, phobias, and posttraumatic stress disorders. He concludes that because hypnosis exploits the intimate connection between mind and body, it provides relief through improved self-regulation and also beneficially affects cognition and the experience of self-mastery. PMID- 2194609 TI - Self-regulation of anxiety. AB - The authors reviewed the literature on biofeedback, self-regulation, and anxiety but found no clinically relevant controlled efficacy studies. None of the controlled studies used a comprehensive self-regulation treatment that included autonomic indices of relaxation, attention to diaphragmatic breathing, daily deep relaxation, and emphasis on using self-regulation during stressful challenge in everyday life. After examining physiological mechanisms associated with anxiety and its self-regulation, the authors describe a comprehensive physiological self regulation treatment package using case presentations of treatment results with various anxiety disorders. PMID- 2194611 TI - How much dietary fat in therapeutic nutrition? AB - Dietary fat has a less prominent role in realimentation than the alternate source of energy, carbohydrate. Presently available therapeutic diets, in typical feeding routines, provide only 3 to 120 g of fat per day. Three major factors contribute to fat underutilization: long-standing belief that fat is to blame for various vague symptoms of indigestion, misconception that daily fecal fat in excess of 7 g represents bowel dysfunction, and fear of fat-induced atherogenesis. None of these apply to refeeding starved and malnourished patients. The small intestine has a vastly underutilized capacity for fat absorption, and at the habitual fat intake of 100 g per day absorption is complete in the proximal one fifth of the gut. In patients requiring vigorous realimentation, the remaining small intestine should also be utilized. Dietary fat is well tolerated, and daily intakes of 500 g of polyunsaturated fat in a complete diet have not been associated with important side effects, while there was a significant improvement in body stores of fat and protein. Compared to diets high in carbohydrate, adequate intake of fat results in better nutrient utilization, less CO2 production and decreased lipogenesis and insulin requirements. Diets higher in fat are also better tolerated because of their lower volume and osmolality. The result is more effective absorption of calories and a faster nutritional recovery. Increased adipose tissue and protein reserve benefits patients who are in stress, immunocompromised, or debilitated. Adequate dietary fat should be considered for malnourished subjects with intact gastrointestinal function, and when intestinal absorptive capacity is reduced by surgery or disease. PMID- 2194612 TI - Advice literature: a Victorian view of sexual mores. PMID- 2194614 TI - Modular construction of nervous systems: a basic principle of design for invertebrates and vertebrates. AB - The modular construction of brain tissue is not solely a feature of vertebrate nervous tissue, but is characteristic of many invertebrate nervous systems as well. Modern vertebrate and invertebrate modules vary over several orders of magnitude in volume but vary less in diameter. Although the physiological and anatomical differences between the modules discussed herein are overpowering, their importance to nervous system functions are similar. Modules are the serial and parallel processing units that have allowed large-brained animals to evolve. Many invertebrate modules are discrete, hemispherical lobes, visible on the surface of the brain or nerve cord, whereas most mammalian modules are columnar or ellipsoidal tissue compartments that can only be visualized with specific anatomical methods. Lobes from the largest invertebrates can be more voluminous than any neocortical compartments, but these large lobes are usually not single modules. Large invertebrate lobes contain internal compartments that are single modules and of similar size to their vertebrate analogs. However, vertebrate cortical modules or columns, are far more numerous than the compartments in invertebrate brains and in several cases are known to be adjoined laterally into slabs of tissue that extend for several millimeters. Physiological data support the idea that neural modules are not just anatomical entities, but are active local circuits. The specific activities within each type of module will depend upon its neuronal components, both intrinsic and extrinsic, its functional roles and phylogenetic history. Many cellular and intercellular phenomena common to vertebrates and invertebrates underlie the development of modules. Neuronal and glial interactions and their interplay with the extracellular environment depend upon families of molecules with broad phyletic occurrences. The commonalities of growth mechanisms may to a large degree account for the widespread incidence of neuronal processing units. The strategy of enlarging a nervous system through the replication of the basic units is thought to be advantageous for several reasons. This plan allows nervous systems to economize on the branch sizes and lengths needed for interconnections, to ensure that appropriate targets are reached during development and to modulate specific circuits within a larger network. PMID- 2194613 TI - Fetal surveillance--update. AB - There are numerous protocols for antepartum fetal heart rate testing. It is pointless to try to determine which is the "best" protocol. Each individual clinician should evaluate the protocols in his institution for applicability to clinical practice. The basic requirements for accurate screening tests should be met by any proposed clinical management scheme, i.e., ease of performance, low false normal rate, acceptable false abnormal rate, knowledge of perinatal outcome, and cost effectiveness. The protocol chosen must then be applied consistently and uniformly. The application of these principles will aid physicians in improving care for their pregnant patients. PMID- 2194615 TI - Fibrositis/fibromyalgia: a difference of opinion. PMID- 2194616 TI - Free radicals and antioxidant systems in health and disease. AB - Free radical (FR) mechanisms have both beneficial and deleterious actions in vivo. Intensive scientific interest in FRs over the last 20 years has led to a clearer understanding of their roles and helped to clarify the contribution of our intrinsic defence systems (antioxidants) in limiting FR-induced tissue damage. As more and more conditions are shown to have a FR aetiology it becomes imperative to develop newer therapies to prevent and treat FR-induced disease. PMID- 2194617 TI - The significance of childhood sexual abuse for adult psychiatry. AB - Childhood sexual abuse is now recognized as a common occurrence, and it has been accepted that in a substantial number of cases victims suffer lasting psychological damage. Many such people are now speaking out and seeking help for the first time. They require sensitive assessment and understanding. Psychotherapy may well be helpful in appropriate cases, although studies of outcome are still lacking. PMID- 2194618 TI - Renal replacement therapy in the ICU: the role of continuous arteriovenous haemodialysis. AB - Conventional haemodialysis is not available on all intensive care units (ICUs) and there are relatively few renally trained nurses able to run haemodialysis machines. Continuous arteriovenous haemodialysis provides effective renal replacement therapy for critically ill patients in the ICU. Unlike continuous arteriovenous haemofiltration it provides sufficient control over electrolyte, solute and water balance to obviate the need for additional treatment with intermittent conventional haemodialysis. PMID- 2194619 TI - Ocular involvement in giant cell arteritis. AB - Giant cell arteritis (GCA) is a systemic disease with a wide spectrum of clinical manifestations. Severe visual loss is the most frequent serious complication. This article reviews current ideas about GCA and in particular its ocular manifestations. PMID- 2194620 TI - Morbidity among anaesthetists. AB - Anaesthetists may be exposed to a number of occupational hazards. These include exposure to infections, environmental pollution with volatile anaesthetic agents and psychological and stress-related illness which may predispose to drug dependence or suicide. PMID- 2194610 TI - Environmental teratogens. AB - By far the largest category of malformations, 65% falls into the group of those with an unknown cause(s). Purely genetic causes of malformations (autosomal and cytogenetic), estimated to produce 20 to 25% of all human malformations, comprise the largest group of congenital malformations with known etiology. Although environmental causes of human malformations account for 10% or fewer of malformations, most of these environmentally induced malformations are related to maternal disease states. Fewer than 1% of all human malformations are related to drug exposure, chemicals, or radiation, but studies of environmentally induced malformations are important because they may teach us how to predict and test for teratogenicity, understand the mechanisms of teratogenesis from all etiologies, and provide a means by which human malformations can be prevented. PMID- 2194621 TI - The arousal hypothesis of schizophrenia: current status. PMID- 2194622 TI - Lung cancer. AB - Lung cancer has increased in importance as a cause of death over the last 60 years. It is now the commonest cancer in the UK, causing over 40,000 deaths per annum or an average of 110 per day. This review considers further aspects of epidemiology, aetiology and clinical features and discusses how we may better select the few who can be cured, so that the remainder receive more appropriate palliative therapy. PMID- 2194623 TI - CNS growth factors. AB - The fundamental importance of polypeptide growth factors in regulating growth and maintaining viability within the CNS is now widely acknowledged. Although the physiological roles of individual growth factors remain to be defined, increasing evidence suggests involvement within the CNS in development, maintenance of neurones, injury responses, the pathogenesis of degenerative diseases and possibly oncogenesis. This review focuses on nerve growth factor and the fibroblast growth factors. PMID- 2194624 TI - Angina-like chest pain: head, heart or oesophagus? AB - Chest pain indistinguishable from angina may arise from causes other than ischaemic heart disease. Careful history-taking may help to clarify the situation but further investigation is often needed. Techniques are now available to help assess those patients with normal coronary angiograms and thus lead to more appropriate management. PMID- 2194625 TI - Autism: current understanding and management. AB - Autism is now generally considered to be an organic neurodevelopmental disorder. This review considers the current understanding of genetic factors and associated medical conditions, together with a discussion of some aspects of management and treatment of affected children and adolescents. PMID- 2194626 TI - Type A behaviour and coronary heart disease: when will the jury return? PMID- 2194627 TI - The aetiology of transient global amnesia. A case-control study of 114 cases with prospective follow-up. AB - A case-control comparison of 114 transient global amnesia (TGA) patients using both normal community-based controls (n = 109) and transient ischaemic attack (TIA) controls (n = 212) showed no evidence of an increased risk of TGA associated with any of the conventional risk factors for cerebrovascular disease. However, migraine was significantly more common in the TGA patients than in either control group. A prospective longitudinal study using actuarial (life table) analysis confirmed that the prognosis of the TGA patients was strikingly better than that of the TIA controls. An important minority (7%) of TGA cases developed epilepsy, usually within one year of presentation. On the basis of this evidence, a thromboembolic aetiology for TGA can be confidently rejected, at least for the vast majority of cases. There are good theoretical reasons to link migraine and TGA casually, and occasionally epilepsy may masquerade as TGA. In the remaining cases the cause remains unknown. PMID- 2194628 TI - Synapses, axonal and dendritic patterns of GABA-immunoreactive neurons in human cerebral cortex. AB - Gamma-aminobutyric acid (GABA) containing neurons were characterized in human association cortex by a combination of Golgi impregnation and immunohistochemistry. Neurons were Golgi impregnated, gold toned, drawn and then classified on the basis of their dendritic and axonal arborization in layers I VI. An antiserum to GABA was used to determine which of the impregnated neurons were immunopositive. Twenty-four GABA-positive cells were Golgi impregnated: 7 were bitufted with their dendrites predominantly radially oriented, and 17 were multipolar stellate cells. Three of the multipolar cells with large somata in the deep layers showed dendritic patterns similar to previously described basket cells. Nine of the multipolar stellate cells in layers III-VI showed characteristics of 'neurogliaform' neurons (Ramon y Cajal, 1899). The somata and the dendritic field of these cells were spherical, with diameters of about 10-15 microns and 200 microns, respectively. Their dendrites were smooth and slightly beaded. The axon collaterals were densely distributed in and around the dendritic field, in a spherical area with a diameter of at least 300 microns. The thin axon collaterals had only occasional 'en passant' swellings. Contacts between the axons of neurogliaform cells and the distal dendrites of Golgi-impregnated pyramidal cells were observed. Electron microscopic immunocytochemistry revealed that GABA immunopositive nerve terminals formed symmetric synaptic contacts with somata, with GABA immunonegative and immunopositive dendritic shafts and with dendritic spines. The results show that GABAergic neurons are heterogeneous with respect to their dendritic and axonal patterns. In addition to the chandelier and basket cells, which have been shown in animal studies to contain GABA, other cell types, most prominently the neurogliaform cells, terminating on the distal parts of neurons, also contain GABA and may have a inhibitory function. Many of the GABAergic terminals make synapses on dendritic spines and shafts in the human cerebral cortex. PMID- 2194629 TI - The effect of prior surgical disconnection of the anterior mediobasal hypothalamus on LHRH release in vitro. AB - The degenerative responses of luteinizing hormone-releasing hormone (LHRH) containing neurons within the mediobasal hypothalamus (MBH) after knife cut lesions (FC) made in the frontal plane of the retrochiasmatic hypothalamus include a reduced number of LHRH-immunoreactive (ir) nerve terminals in the median eminence, reduction in LHRH content of the MBH and growth of novel irLHRH containing neural processes into FC scar tissue. We have now investigated basal and secretogogue-evoked LHRH release in vitro from the preoptic area-MBH (POA MBH) of adult male rats at 10 or 60 days after FC. Basal LHRH release rate (P less than 0.05) and total (P less than 0.01) amount released 60 days after FC were reduced when compared to control (CONT) hypothalami, but not shams. A 30 min pulse of naloxone (NAL, 1 mg/ml) stimulated greater than 2-fold relative increase in LHRH release for all groups; however, the total amount of LHRH released by FC hypothalami was less (P less than 0.05) than that of CONT, but not sham POA-MBHs. Although exposure to elevated KCl significantly increased (P less than 0.01) LHRH release for all 3 groups, the FC secretory response was less than that of both CONT (P less than 0.05) and sham (P less than 0.01) groups. In the second experiment single POA-MBH were perifused at 10 days (sham and FC) or 60 days (CONT, sham and FC) after surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2194630 TI - Anatomical distribution of LHRH-immunoreactive neurons in the human infant hypothalamus and extrahypothalamic regions. AB - The morphological features and distribution of luteinizing hormone-releasing hormone (LHRH)-immunoreactive cell bodies and fibers of the hypothalamic and the neighboring mesencephalic regions were studied in the normal newborn infant by immunohistochemistry. Within the hypothalamus, numerous LHRH-immunoreactive like (IL) cell bodies were found mainly in the ventral portion of the infundibular nucleus close to the median eminence and at a lower extent in the medial preoptic area. In addition, sparse immunoreactive cell bodies were displayed in the paraventricular and medial mammillary nuclei. The mesencephalon also exhibited rare immunoreactive cell bodies in the periaqueductal gray. LHRH-IL fibers, predominantly varicose, formed a continuum from the septo-preoptico level to the mesencephalon. In the hypothalamus, the median eminence exhibited the highest LHRH innervation. LHRH-IL fibers are also observed in the lamina terminalis, the medial preoptic area, the suprachiasmatic, the supraoptic, the peri- and the paraventricular nuclei. In the last two nuclei, some fibers projected to the dorsomedial and ventromedial nuclei whereas others were in close relation with the ependyma. The mesencephalon displayed low LHRH-IL fibers, present essentially in the raphe and interpeduncular nuclei and around the ependyma. When compared with data obtained in other mammals, the present findings agree well with the general distribution and morphological features of LHRH-IL neuronal structures reported elsewhere. PMID- 2194631 TI - S-100B but not NGF, EGF, insulin or calmodulin is a CNS serotonergic growth factor. AB - The effects of S-100B, nerve growth factor (NGF), epidermal growth factor (EGF) and insulin were tested in cultured mesencephalic neurons. Only chronic S-100B showed enhancement (maximal at 3.2 ng/ml is 171%) after 3 days of incubation of the [3H]5-HT uptake capacity by serotonergic neurons. A single application at initial plating of S-100B (maximal at 5 ng/ml is 185%), but not calmodulin, increased the development of the [3H]5-HT uptake capacity by the cultured serotonergic neurons. Morphometric analysis of cultured 5-HT immunoreactive (IR) neurons showed an increase (135 and 147%) in neurite length 30 h after S-100B application of 16 and 3.2 ng/ml (respectively). These results suggest that S-100B is a serotonergic growth factor in the mammalian brain. PMID- 2194632 TI - [Mechanisms of molecular action of volatile anesthetics: theories, controversies, implications]. PMID- 2194633 TI - [The use of a fiberscope for difficult intubations in pediatrics]. PMID- 2194634 TI - [Perioperative hypertensive attacks in neurosurgery: basic control measures]. PMID- 2194635 TI - [Symptomatic analgesic treatments of the chronic pain of obliterating arteriopathy]. PMID- 2194636 TI - The role of activated T lymphocytes in gastrointestinal disease. AB - Activated T cells can be visualized in the intestinal lamina propria in a number of gastrointestinal diseases including food-sensitive enteropathy (coeliac disease), inflammatory bowel disease and intractable diarrhoea of infancy. Experimental studies have shown that T-cell activation in human intestinal lamina propria in vitro produces an increase in crypt cell proliferation, villous atrophy, increased HLA-DR expression on enterocytes, increased intra-epithelial lymphocyte numbers, and phenotypically, macrophage activation. All of these features are seen in human gastrointestinal disorders and it is proposed that T cell activation to wheat (in coeliac disease), milk (cows' milk-sensitive enteropathy), and unidentified luminal antigens (Crohn's disease) plays a primary role in the pathogenesis of these disorders. PMID- 2194637 TI - [Scales for the analysis of health care provision]. AB - Geographic analysis of the provision of health care has various levels. The inter country level is suitable for observing flows of health personnel crossing national borders. At the national level, a variety of health facilities management policies may be observed in different regions. The regional level may be used for evaluating access to services, in particular those between rural and urban areas, or even between cities of the same size. Disparities of access to services may be accompanied by gaps between the provision of and the need for services. At a lower level, France has the level of "canton." Nevertheless, this is not always relevant, especially for observing secondary and tertiary care. Data gathered at the "municipalite" level are more precise, in that they allow analysts to follow the circulation of patients. However, this is expensive, and does not go beyond the resource assessment stage. On the basis of fieldwork, one can subdivide the territory into units characterized by specific relations, e.g., those of care providers and the corresponding population. Such mapping crosses conventional administrative limits and emphasizes different social groups and their organization. PMID- 2194638 TI - Information technology. A priority for nursing research. AB - The importance of information technology for health care organizations has been recognized for some time. The major emphasis has been on the development and implementation of technology for financial control and other health care management purposes. The need for nursing information systems has been assessed by nurse experts in recent years and the available clinical systems have been found wanting. This paper reviews research on information technology as a priority for nursing and the actions taken by the National Center for Nursing Research to develop a national agenda for nursing information systems research. PMID- 2194639 TI - ViVACCy--a drug schedule based on G2 blockade and prolonged infusion of multiple tubulin-binding agents. A pilot study. AB - A drug schedule has been devised based on a strategy of G2 blockade followed by prolonged infusion of tubulin-binding agents. The regimen consists of doxorubicin 32 mg/m2 i.v. and cyclophosphamide 320 mg/m2 i.v. on day 1 followed by vinblastine (0.3 to 1.2 mg/m2/day), cisplatin (3 to 12 mg/m2/day), and vincristine (0.04 to 0.16 mg/m2/day) by continuous intravenous infusion on days 5 to 12. Courses are repeated every 28 days. Eighteen patients with advanced solid tumors received 37 courses of chemotherapy in a pilot study to determine safe drug concentrations for the three-drug infusion for 7 days. Dose limiting toxicity was myelosuppression. Patients who received prior mitomycin-C experienced more profound thrombocytopenia than those who did not. Nonhematologic toxicities included mild nausea, vomiting, and transient elevations of serum alkaline phosphatase and serum creatinine. One patient with squamous cell carcinoma of the esophagus who erroneously received vincristine 0.8 mg/m2 instead of 0.08 mg/m2 for 4 1/2 days developed transient myalgia, ileus, and a transient peripheral neuropathy; the patient achieved a sustained complete remission for 15 months and died of unrelated causes. Minor responses and stable disease were seen in two patients with renal cell carcinoma (1 and 2.5 months), three patients with colorectal carcinoma (1.5, 2, and 4 months), and one patient with squamous cell carcinoma of the tongue (2 months). The ViVACCy drug regimen can be given without undue toxicity and may be active in solid tumors. PMID- 2194640 TI - Mitoxantrone for refractory and relapsed acute leukemia. AB - Seventy-seven patients with relapsed or refractory acute leukemia and three with acute blastic chronic myeloid leukemia (CML) were treated in an open Phase II study using mitoxantrone 12 mg/m2 intravenously daily X 5 days. Complete remission (CR) was achieved in 32 of 80 (40%), including 23/45 (52%) with relapsed acute nonlymmphocytic leukemia (ANLL), four of 12 (33%) with relapsed acute lymphocytic leukemia ALL, four of 17 (24%) with ANLL refractory to daunorubicin + cytosine arabinoside, and one of three (33%) with refractory ALL. None of the patients with acute blastic CML achieved CR. Median survival time for all patients was 121 days. Median duration of complete response was 303 days with ten of 32 patients in continuing CR for periods varying from 44+ to 1210+ days. Apart from moderately prolonged hematologic suppression toxicity was mild and subjective side effects were tolerable. Mitoxantrone is an active agent in the treatment of acute leukemia and demonstrates incomplete cross resistance with duanorubicin. Mitoxantrone should be considered for first-line therapy in ANLL. PMID- 2194642 TI - A randomized, double-blind comparison of the antiemetic effect of metoclopramide and lorazepam with or without dexamethasone in patients receiving high-dose cisplatin. AB - Thirty-seven patients with advanced incurable malignancies who were receiving their first course of cisplatin (greater than or equal to 90 mg/m2 bolus), alone or in combination with other antineoplastic agents, were entered in this randomized, double-blind study to determine the antiemetic efficacy of the addition of high-dose dexamethasone to lorazepam plus metoclopramide. All patients received lorazepam (1.5 mg/m2) and metoclopramide (2.0 mg/kg) intravenously (IV) 30 minutes before cisplatin, with the same dose of metoclopramide repeated 1.5, 3.5, 6.5, and 9.5 hours after the 30-minute cisplatin infusion. Patients were randomized to receive dexamethasone (0.5 mg/kg) or placebo by slow bolus injection 30 minutes before cisplatin. All patients were hospitalized for 24 hours and evaluated by observation after cisplatin and a patient questionnaire before discharge. Eighteen patients received metoclopramide and lorazepam without dexamethasone: six (33%) reported no vomiting and four (22%) reported no nausea or vomiting. Nineteen patients also received dexamethasone: 14 (74%) had no vomiting and 13 (68%) reported no nausea or vomiting. These differences were statistically significantly different (P = 0.013 and 0.005, respectively). The side effects attributable to the antiemetic regimen were somnolence (100%), confusion (8%), and diarrhea (46%), and were the same in both arms. Dexamethasone significantly improved the antiemetic efficacy of metoclopramide plus lorazepam without adding toxicity. This three-drug combination gave a high rate of control of acute emesis induced by high-dose cisplatin. PMID- 2194641 TI - Mitoxantrone/high-dose Ara-C and recombinant human GM-CSF in the treatment of refractory non-Hodgkin's lymphoma. A pilot study. AB - Previous study has shown that the combination of mitoxantrone (Novantrone, NO) and Ara-C (AC) (NOAC) was active in refractory non-Hodgkin's lymphoma (NHL) but myelosuppression was dose-limiting. In a pilot study, we investigated the effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) after NOAC chemotherapy in patients with refractory NHL. NO was applied at a dosage of 10 mg/m2/day on days 2 and 3 and AC at 3 g/m2/12h on days 1 and 2. RhGM CSF was administered at 250 ug/m2/day as a continuous i.v. infusion from day 6 until the neutrophils were greater than 3.0/nl for 3 consecutive days. Twenty three patients from five of the nine participating centers were treated with NOAC chemotherapy plus rhGM-CSF, whereas 14 patients from the other four centers received chemotherapy alone. With rhGM-CSF, the median duration of severe neutropenia (less than 0.5/nl) after NOAC was 8 days versus a median of 13 days without rhGM-CSF (P = 0.0058), and that of thrombocytopenia (less than 20.0/nl), 3 days versus 7 days (P greater than 0.4, NS). The rates of infections and stomatitis were 25% and 17%, respectively, for patients treated with rhGM-CSF as compared to 53% (P = 0.0547, NS) and 60% (P = 0.0078), respectively, without rhGM CSF. The following side effects were associated with the administration of rhGM CSF: pleural and/or pericardial effusions in five patients, thrombosis in two patients, bone pain in two patients, and respiratory distress syndrome in one patient. A complete remission was achieved in nine of the 23 patients treated with NOAC plus rhGM-CSF, and in two of the 14 patients treated with chemotherapy alone. The median survival of patients treated with rhGM-CSF was not reached at 400 days and seemed to be longer than that of patients treated with chemotherapy alone (median, 109 days; P = 0.036). RhGM-CSF after chemotherapy can be applied safely to patients with NHL, shorten the period of severe cytopenia, reduce the rates of stomatitis, and did not seem to cause adverse effects on response. PMID- 2194643 TI - Soft tissue sarcoma. Integration of brachytherapy, resection, and external irradiation. AB - Between December 1981 and August 1988, 63 patients with clinically localized nonretroperitoneal soft tissue sarcomas underwent 65 brachytherapy procedures in conjunction with conservative resection with (61 tumors) or without (four tumors) external beam irradiation. Implant doses of 1500 to 2000 cGy were combined with 4500 to 5000 cGy of external irradiation. External irradiation was given preoperatively for larger lesions near bone or neurovascular structures, whereas it was used postoperatively for smaller, more resectable lesions or those that had previously been inadequately excised. There were 47 high-grade tumors, 34 tumors greater than 5 cm, and nine patients with recurrent lesions (five with previous irradiation). With mean follow-up of 20 months, conclusions on local control are tentative, but only two of 56 tumors (4%) with brachytherapy as part of initial management had recurred locally and three of nine recurrent tumors had re-recurred locally. Only one of five local recurrences was within the implanted volume. Only two of 40 implantations (5%) performed at initial resection followed by postoperative external irradiation led to wound complications, whereas four of 16 implantations (25%) performed at resection after preoperative external irradiation were associated with wound problems. This technique does not increase local morbidity and may enhance local tumor control in comparison with either external radiation or brachytherapy alone as an adjuvant to conservative resection. PMID- 2194644 TI - Management of superficial squamous cell carcinoma of the lip with Mohs micrographic surgery. AB - Forty-one patients were treated with Mohs micrographic surgery for well differentiated superficial squamous cell carcinoma of the lip; 34 had closure of their surgical site by a mucosal advancement flap, and five were allowed to heal by second intention. Cases were limited to T1N0M0 or T2N0M0, these being early superficial lesions. Primary closure by mucosal advancement provides cosmetic and functional healing for these lesions. The combination of Mohs micrographic excision and mucosal advancement closure may be considered standard office or outpatient surgical management of these common tumors. PMID- 2194646 TI - S-phase fraction of human prostate adenocarcinoma studied with in vivo bromodeoxyuridine labeling. AB - Forty-six patients with adenocarcinoma of the prostate were given an intravenous infusion of the thymidine analogue, bromodeoxyuridine (BrdU), 200 mg/m2, at the time of needle biopsy or transurethral resection to label tumor cells in the DNA synthesis phase. The tumor specimens were stained by an indirect immunoperoxidase method with anti-BrdU monoclonal antibody. The BrdU labeling index, S-phase fraction, was determined by counting the number of BrdU-labeled cells in the tissue sections. S-phase fraction correlates with the results of histologic tumor grade, Gleason score, and growth patterns. The higher S-phase fraction may indicate biologic malignancy. Moreover, the degree of heterogeneity concerning S phase fraction distribution within prostate cancer tissue could be evaluated and the findings compared with the morphologic appearance. The authors results suggest that the measurement of BrdU labeling index in prostate cancer may prove to be a new objective and quantitative assay for biologic potential of individual tumors. PMID- 2194645 TI - Abnormalities of lectin histochemistry in familial polyposis coli and hereditary nonpolyposis colorectal cancer. AB - A transformation in the composition of colonic glycoconjugates has been described in adenomas, carcinomas, and certain premalignant conditions. These changes have been detected histochemically by the labeling patterns of fluorescein-conjugated lectins, which bind specific carbohydrate structures on fixed tissue sections. This study was performed to determine whether abnormal lectin binding patterns are present in tissues from patients genetically predisposed to colonic neoplasms and whether these patterns could be used as phenotypic markers for inheritance of the genotype. Lectin staining patterns of 22 colectomy specimens from patients with familial polyposis coli (FPC) and rectal biopsy specimens from 47 patients at risk for hereditary nonpolyposis colorectal cancer (HNPCC) (also known as Lynch syndromes I and II) were compared with rectal biopsy specimens from 27 sex matched controls. The fluorescein-conjugated lectins included the agglutinins derived from peanut, Dolichos biflorus, Ulex europeus, and wheat germ (including the succinylated derivative). Using a technique for quantitating lectin binding on the tissue sections that provided a score from 0 to 400, labeling with certain lectins was found to vary slightly as a function of age and sex. Histologically normal mucosa from patients with FPC bound significantly less wheat germ agglutinin but significantly more U. europeus and succinylated wheat germ agglutinins than controls. Adenomas and dysplastic flat mucosa from the colectomy specimens of patients with FPC showed significantly less binding with D. biflorus, succinylated wheat germ, and wheat germ agglutinins than controls. Rectal tissues from patients at risk for HNPCC were found to bind significantly less peanut agglutinin and D. biflorus agglutinin than controls. Of interest, staining of the tissues by peanut and wheat germ lectins increased as a function of patient age; the control subjects were older than the patients with familial colon cancer, which could possibly account for the observations made with these two lectins. These results provide evidence that the premalignant colonic epithelium in familial polyposis and the hereditary nonpolyposis colon cancer syndromes may be biologically different and indicate that glycoconjugate modifications are early events in the evolution of the neoplastic phenotype. PMID- 2194648 TI - Changes in breast self-examination behavior achieved by 89,835 participants in the Canadian National Breast Screening Study. AB - Breast self-examination (BSE) behavior was analyzed in 89,835 participants in the National Breast Screening Study (NBSS) of whom 64,619 were eligible for annual rescreening and 25,216 were followed by mail after a single screen exam. Among those eligible for rescreening, BSE competence scores based on seven BSE criteria significantly improved over time and correlated directly with reported BSE frequencies. Among all participants, the proportion reporting BSE frequencies of greater than or equal to 12/year increased over time from approximately 20% on entry to 50% to 64% at final screen. Similarly, reports of zero frequency diminished from 50% to 10% to 15%. Variables such as educational status, age (fifth versus sixth decades), eligibility for mammography, smoking history, and ethnic origin had negligible or no influence on BSE competence. However, women with first-degree relatives with breast cancer had significantly higher BSE scores. NBSS experience suggests that most women who enter screening programs will upgrade their BSE skills if subjected to brief episodes of repeated BSE instruction. PMID- 2194647 TI - Malignant histiocytosis. A reassessment of cases previously reported in 1975 based on paraffin section immunophenotyping studies. AB - Malignant histiocytosis (MH) is a term that has been used to describe a syndrome in which there is a systemic proliferation of cells that have the cytologic appearance of atypical histiocytes. Biopsy materials from 15 patients with malignant lymphoma diagnosed as malignant histiocytosis in a previous study reported in 1975 were analyzed by a panel of antibodies and reclassified using current nosologic concepts of malignant lymphoma. The antibodies used comprised reagents detecting a formalin-resistant epitope on B-cells (L26), T-cells (anti CD3, anti-leu 22 [CD43], and UCHL1 [CD45RO]), monocyte/macrophage-derived cells (KP1 [CD68]), as well as antibodies that detect leukocyte common antigen (PD7 [CD45RB]), and a formalin-resistant epitope of Ki-1 (Ber-H2 [CD30]). The authors found that nine lymphomas had a profile consistent with T-lineage, including six in which Ki-1 (CD30) was coexpressed, and two were B-lineage. Three lymphomas showed no specific lineage characteristics although two were Ki-1 (CD30) positive, and none had expression of KP1 (CD68). The 12 lymph node biopsy specimens showed a variety of patterns of involvement, including sinusoidal, paracortical, and diffuse; the spleens showed predominantly red pulp involvement. A 15th case was believed most consistent with a virus-associated hemophagocytic syndrome. These findings support previous suggestions that the majority of cases diagnosed as MH represent T-lineage-associated hematolymphoid neoplasms, and that only a rare case will be of monocyte/macrophage origin. It is suggested that the term MH be subsumed under the rubric of large cell lymphoma and unless there are compelling immunohistochemical data to support a histiocytic origin, that the term MH be abandoned in favor of a more accurate descriptive term, such as sinusoidal large cell lymphoma. PMID- 2194649 TI - Inflammatory pseudotumor of spleen. AB - The case of a 66-year-old man with pseudotumor of the spleen is presented. This rare entity can mimic malignant lymphoma clinically and radiographically. Splenectomy is diagnostic and curative. The etiology of pseudolymphoma is unknown, although a review of the literature suggests an association with prior systemic bacterial infection, as in the present case. PMID- 2194650 TI - Development of antiestrogens and their use in breast cancer: eighth Cain memorial award lecture. AB - This paper describes the laboratory discovery and clinical testing of the first nonsteroidal antiestrogen, MER-25 (ethamoxytriphetol). The compound blocks estrogen action in all species tested and has only slight but transient estrogenic effects. No other antisteroidal actions are noted. MER-25 is antiestrogenic in primates and was investigated in the clinics in a wide range of gynecological conditions, including breast and endometrial cancer. Unfortunately toxic side effects (hallucinations, etc.) precluded further investigation. A derivative of triphenylethylene, clomiphene, has some partial agonist (estrogen like) actions in laboratory animals and following clinical evaluation is now an established agent for the induction of ovulation in subfertile women. Although clomiphene is active in advanced breast cancer, it was not developed further. In the late 1960s a related compound, tamoxifen, was evaluated to treat a number of estrogen-responsive disorders but was successfully introduced in the 1970s for the treatment of advanced breast cancer. Although there was only modest initial interest in the palliative use of tamoxifen, an enormous increase in basic and applied studies with antiestrogens resulted in a definition of the target site specific and tumoristatic actions of tamoxifen. Close cooperation between laboratory and clinical evaluation has guided the subsequent development of tamoxifen which is now available to treat all stages of breast cancer. Long-term adjuvant tamoxifen therapy, a concept developed in the laboratory, is currently the treatment strategy of choice. The considerable success of tamoxifen has focused attention on new antiestrogens with different pharmacological properties for other potential clinical applications. PMID- 2194651 TI - Anthracycline antibiotics with high liposome entrapment: structural features and biological activity. AB - We evaluated the entrapment of 21 different water-insoluble aglycones or anthracycline antibiotics in multilamellar liposomes composed of dimyristoyl phosphatidyl choline and dimyristoyl phosphatidyl glycerol at a 7:3 molar ratio. The drug:lipid weight ratio was 1:15 to 1:50. The different analogues tested were modified at position 4 in the aglycone portion (4-demethoxy) and/or positions 2' (halo), 3' (hydroxy, acetoxy), or 4' (epi, acetoxy) in the sugar portion. The entrapment efficiency was assessed by measuring the amount of free drug remaining in the supernatant after centrifugation of the liposomes and by direct examination of the pellets by fluorescent microscopy. Optimal entrapment (greater than 98%) was observed with only four compounds: 4-demethoxyadriamycinone; 2' iododaunorubicin; 4-demethoxydaunorubicin; and 2'-iodo-3'-hydroxy-4'-epi-4 demethoxydoxorubicin (Compound 22). All other compounds showed significant drug precipitation outside the multilamellar vesicles when observed by fluorescent microscopy. Compound 22, entrapped in liposomes, was evaluated in vivo against i.p. L-1210 leukemia by the i.p. route, and liver metastases of M5076 reticulosarcoma by the i.v. route. In both models, liposome-entrapped Compound 22 was more active than doxorubicin at the optimal dose [median survival (given in percentage) of treated to control animals was for L-1210, greater than 600 versus 212; for M5076, 200 versus 133]. 4-Demethoxy and 2'-iodo are structural modifications that markedly enhance the affinity of anthracycline antibiotics for lipid bilayers without compromising biological activity. These findings will serve as a guideline to obtain liposome-anthracycline preparations, with optimal formulation characteristics, enhanced tumor-targeting properties, and non-cross resistance with doxorubicin. PMID- 2194652 TI - Pharmacokinetics of continuous infusion of methotrexate and teniposide in pediatric cancer patients. AB - Laboratory studies have demonstrated the ability of teniposide to markedly enhance the intracellular accumulation of methotrexate suggesting that combination therapy with these agents may produce clinical benefit. Studies of methotrexate and teniposide were conducted in 19 children with relapsed acute lymphocytic leukemia to evaluate the pharmacokinetics of this previously untested combination of agents given alone or in combination and to demonstrate the feasibility of a Bayesian dose optimization strategy. Patients were randomly assigned to receive intermediate dose methotrexate as a 24-h continuous infusion, administered either simultaneously with continuous infusion teniposide or sequentially with the teniposide infusion beginning 12 h after the end of the methotrexate infusion. Plasma samples were obtained during and after infusions at appropriate times for a comprehensive pharmacokinetic study of each drug. Two measured drug concentrations obtained during the infusion were used to adjust each patient's dose rate to achieve target values of 10 microM for methotrexate and 15 microM for teniposide. Pharmacokinetic parameters for teniposide were not different for patients given simultaneous methotrexate from parameters estimated for patients receiving teniposide 12 h after the end of the methotrexate infusion. Despite similar end of infusion methotrexate concentrations, 24-h postinfusion methotrexate concentrations were lower (0.137 versus 0.235 microM; P less than 0.05) in the patients receiving simultaneous infusions. The patient specific dose regimens yielded acceptably precise, minimally biased steady state drug concentrations. These pharmacokinetic results provide the basis for further clinical studies with this combination of antileukemic agents. PMID- 2194653 TI - Reduction in the frequency of activated ras oncogenes in rat mammary carcinomas with increasing N-methyl-N-nitrosourea doses or increasing prolactin levels. AB - The role of c-Ha-ras-1 oncogene activation in the multistage biological process of N-methyl-N-nitrosourea (NMU)-induced mammary carcinogenesis was investigated. The average yield of NMU-induced mammary tumors in Wistar-Furth rats was altered by modification of either the initiation or promotion/progression stage of carcinogenesis. Initiation was varied by the use of different doses of NMU from 20 to 50 mg/kg. Tumor yield was increased with increasing NMU doses. However, the frequency of mammary tumors with activated c-Ha-ras-1 decreased in a linear fashion with increasing NMU doses. Promotion/progression was varied by increasing prolactin levels starting approximately 2 weeks after NMU administration. This hormonal manipulation increased tumor yield, while reducing the frequency of tumors with activated ras. It is postulated that ras activation represents one of several possible mechanisms by which NMU initiates mammary carcinogenesis. Furthermore, initiated cells without activated ras are more dependent on epigenetic promotional events provided by either prolactin or NMU than are ras initiated cells. PMID- 2194654 TI - Metabolic activation of the potent mutagen, 2-naphthohydroxamic acid, in Salmonella typhimurium TA98. AB - The objective of the present study was to explore the mechanisms responsible for the strong, direct-acting mutagenicity of 2-naphthohydroxamic acid (NHA) for Salmonella typhimurium TA98. NHA was converted to its O-acetate (O-Ac-NHA) by acetyl-CoA, in the presence of competent or heat-treated cell-free bacterial preparations. O-Ac-NHA, which is more mutagenic than NHA, reacted nonenzymatically with tRNA in neutral solutions with retention of both the naphthyl and carbonyl groups in the products, but NHA did not react. Enzymatic sulfate conjugation was not demonstrated. TA98 cells converted NHA to 2 aminoaphthalene, presumably through a Lossen rearrangement following O acetylation or conjugation by other metabolic pathways. TA98 cells reduced O-Ac NHA to 2-naphthamide, and NADH and NADPH were shown to be cofactors for reduction in the presence of a cell-free bacterial preparation. Although horseradish peroxidase and H2O2 catalyzed the binding of these compounds to tRNA, no evidence of oxidation of NHA or O-Ac-NHA was obtained with H2O2 and cell-free preparations of TA98 or the cells themselves, as judged by the lack of formation of the peroxidative product, 2-naphthoic acid. Both NHA and O-Ac-NHA reacted with DNA of TA98 with retention of both naphthyl group and carbonyl of the naphthoyl moiety in the adduct(s). These results suggest that NHA may be activated in TA98 by esterification, and the resulting metabolites may amidate or carbamoylate nucleic acids. PMID- 2194655 TI - Workshop on linkage studies of hereditary breast cancer. PMID- 2194656 TI - Concentration of antimicrobial proteins in human saliva. The effect of long-term usage of a zinc-containing dentifrice on the protein composition of stimulated saliva from 198 children. PMID- 2194657 TI - The role of extracellular calcium in the regulation of intracellular calcium and cell function. PMID- 2194658 TI - Regulation of cytosolic calcium by extracellular divalent cations in C-cells and parathyroid cells. PMID- 2194659 TI - Monoclonal antiparathyroid antibodies--tools for studies of the regulation of cytoplasmic calcium and function of parathyroid and other antibody-reactive cells. PMID- 2194660 TI - Ca2(+)-sensing, second messengers, and the control of parathyroid hormone secretion. PMID- 2194661 TI - Control of renin secretion by extracellular calcium. PMID- 2194662 TI - Accuracy of subjective and computer-assisted assessments of angiographic left ventricular regional wall motion. AB - To evaluate the accuracy of angiographic methods for analysis of left ventricular regional wall motion, we measured the ability of a carefully performed subjective analysis (three independent observers) and that of three computer-assisted methods (centerline, radial, and area) to detect the presence of significant coronary artery disease. Normal ranges were established in 90 studies showing normal wall motion, and accuracy was tested in a second, consecutive series of 43 ventriculograms. The results show that the subjective method best separated those regions with from those without significant coronary disease. The subjective method also demonstrated sensitivity comparable to the centerline and radial methods. Among the computer-assisted methods, the area method was least sensitive but most specific for both anterior and inferior region coronary disease. The centerline and radial methods were highly sensitive, but less specific. When coronary disease was defined by electrocardiographic Q-waves, the area method had superior accuracy. Further analysis showed the following: 1) For the centerline and radial methods, long-axis reregistration of the end-systolic frame resulted in loss of sensitivity but increased specificity for anterior wall coronary disease, and little change in analysis of the inferior wall; 2) inclusion or exclusion of the apex had little effect on predictive accuracy for anterior wall coronary disease; 3) as expected, sensitivity and specificity results of all methods were dependent on the selection of a normal range cutoff value; but when performance was optimized, the subjective and area methods had a higher overall predictive accuracy than the centerline method; 4) It is likely that all three computer-assisted methods could be calibrated to give indications of degrees of hypokinesis, as their results correlated well with subjective observers' evaluations over the entire range of scores. These results should assist in selection of the optimal method for regional wall motion analysis in clinical and research applications. As currently applied, the area method is the most specific of the computer-assisted methods tested; the centerline and radial methods have highest sensitivity and therefore are most suited to detection of mild degrees of hypokinesis. PMID- 2194663 TI - Left-sided inferior vena cava draining into the coronary sinus via persistent left superior vena cava: case report and review of the literature. PMID- 2194664 TI - Commitment and activation at pol II promoters: a tail of protein-protein interactions. PMID- 2194665 TI - Analysis of structure-function relationships of yeast TATA box binding factor TFIID. AB - A systematic series of N-terminal, C-terminal, and internal deletion mutants of S. cerevisiae TFIID were expressed in vitro and tested for TATA box binding and basal level transcription activities using, respectively, DNA mobility shift and in vitro transcription assays. The domains responsible for these activities were colocalized to a surprisingly large region containing C-terminal residues 63-240. This region was noted previously to contain potentially interesting structural motifs (central basic core, direct repeats, and sigma factor homology) and, more recently, to be highly conserved among TFIID from different species. Deletion mutant cotranslation studies revealed that TFIID binds DNA as a monomer. The implications of these results for TFIID structure and function are discussed. PMID- 2194666 TI - Isolation and characterization of the Drosophila gene encoding the TATA box binding protein, TFIID. AB - To investigate the biochemical mechanisms involved in interactions between regulatory factors and the general transcription complex, we have cloned, expressed, and characterized the Drosophila gene encoding the TATA binding protein, dTFIID. Comparison of the protein sequences of the Drosophila and yeast TATA binding proteins reveals a bipartite organization consisting of a highly conserved, basic carboxy-terminal domain and a nonconserved amino-terminal region rich in Gln, Gly, Ser, and Met residues. Purified dTFIID protein binds specifically to the TATA sequence and activates basal-level transcription, and the conserved carboxy-terminal half of the molecule is sufficient for both activities. Partially purified TFIID from Drosophila cells mediates activation by the transcription factor Sp1. In contrast, purified dTFIID expressed from the cloned gene is unable to support Sp1-dependent activation, suggesting that other factors may be required to mediate interactions between upstream activators like Sp1 and the TATA binding protein. PMID- 2194667 TI - Mechanism of transcriptional activation by Sp1: evidence for coactivators. AB - In reconstituted reactions, Sp1 stimulates transcription at TATA-containing promoters in the presence of semipurified TFIID fractions from either human or Drosophila cells, but is unable to do so when these fractions are replaced by purified, cloned Drosophila or yeast TFIID. Our findings with Sp1 and CTF suggest that partially purified TFIID fractions from human and Drosophila cells contain coactivators that are dispensable for basal transcription but are required as molecular adaptors between trans-activators and the general transcription initiation machinery. Experiments using cloned TFIID proteins suggest that these coactivators function through the amino-terminal portion of TFIID and that coactivator-TFIID interactions are species specific. At promoters lacking a TATA box, an additional activity distinct from coactivators is required for Sp1 activation of transcription. PMID- 2194668 TI - A T. cruzi-secreted protein immunologically related to the complement component C9: evidence for membrane pore-forming activity at low pH. AB - Protozoan parasite T. cruzi invades cells within acidic vacuoles, but shortly afterward escapes into the cytosol. Exit from the phagosome is blocked by raising the pH of acidic compartments, suggesting that a previously described acid-active hemolysin secreted by T. cruzi might be involved in the membrane disruption process. Here we show that T. cruzi supernatants are cytotoxic for nucleated cells at pH 5.5 and contain a protein reactive with antibodies against reduced and alkylated human C9 (the ninth component of complement). The C9 cross-reactive protein (TC-TOX) copurified with the cytolytic activity, and the active fractions induced conductance steps characteristic of transmembrane ion channels in planar phospholipid bilayers. Immunocytochemical studies using antibodies against purified TC-TOX showed that the protein was localized to the luminal space of parasite-containing phagosomes. We postulate that TC-TOX, when secreted into the acidic environment of the phagosome, forms pores in the membrane, which contribute to its disruption. PMID- 2194669 TI - Gamma-tubulin is a component of the spindle pole body that is essential for microtubule function in Aspergillus nidulans. AB - We have recently discovered that the mipA gene of A. nidulans encodes gamma tubulin, a new member of the tubulin superfamily. To determine the function of gamma-tubulin in vivo, we have created a mutation in the mipA gene by integrative transformation, maintained the mutation in a heterokaryon, and determined the phenotype of the mutation in spores produced by the heterokaryon. The mutation is lethal and recessive. It strongly inhibits nuclear division, less strongly inhibits nuclear migration, and, as judged by immunofluorescence microscopy, causes a reduction in the number and length of cytoplasmic microtubules and virtually a complete absence of mitotic apparatus. We conclude that gamma-tubulin is essential for microtubule function in general and nuclear division in particular. Immunofluorescence microscopy of wild-type hyphae with affinity purified, gamma-tubulin-specific antibodies reveals that gamma-tubulin is a component of interphase and mitotic spindle pole bodies. We propose that gamma tubulin attaches microtubules to the spindle pole body, nucleates microtubule assembly, and establishes microtubule polarity in vivo. PMID- 2194670 TI - ERD2, a yeast gene required for the receptor-mediated retrieval of luminal ER proteins from the secretory pathway. AB - Resident proteins of the ER lumen carry a specific tetrapeptide signal (KDEL or HDEL) that prevents their secretion. We have previously described the isolation of yeast mutants that fail to retain such resident proteins within the cell. Here we describe ERD2, a gene required for retention. It encodes a 26 kd integral membrane protein whose abundance determines the efficiency and capacity of the retention system. Reduced expression of ERD2 leads to secretion of proteins bearing the HDEL signal, whereas overexpression of ERD2 improves retention both in wild-type cells and in other mutants. These results are consistent with other evidence that ERD2 encodes the HDEL receptor (see accompanying paper). The gene is also required, perhaps indirectly, for normal protein transport through the Golgi, and hence for growth. We discuss possible roles for ERD2 in the secretory pathway. PMID- 2194671 TI - The ERD2 gene determines the specificity of the luminal ER protein retention system. AB - Luminal ER proteins carry a signal at their C terminus that prevents their secretion; in S. cerevisiae this signal is the tetrapeptide HDEL. Indirect evidence suggests that HDEL is recognized by a receptor that retrieves ER proteins from the secretory pathway and returns them to the ER, and a candidate for this receptor is the product of the ERD2 gene (see accompanying paper). We show here that presumptive ER proteins from the budding yeast K. lactis can terminate either with HDEL or, in the case of BiP, with DDEL. S. cerevisiae does not efficiently recognize DDEL as a retention signal, but exchange of its ERD2 gene for the corresponding gene from K. lactis allows equal recognition of DDEL and HDEL. Thus the specificity of the retention system is determined by the ERD2 gene. We conclude that ERD2 encodes the receptor that sorts luminal ER proteins. PMID- 2194672 TI - Leukocyte adhesion to endothelium in inflammation. PMID- 2194673 TI - Transgenic mice with intracellular immunity to influenza virus. AB - We have generated transgenic mice that express the intracellular anti-influenza virus protein Mx1 under control of an interferon-responsive regulatory element. Upon infection with influenza virus, mice of a high responder line produce Mx1 protein locally at the sites of initial viral replication, exhibit little viral spread, and survive infection. Mice of a low responder line show more extensive viral spread and survive infection only when virus is given at high doses. To survive low dose infections, these mice require injection of interferon along with virus. The results show that influenza viral pathogenesis is determined by a subtle balance between the dose of the infecting virus and the levels of the antiviral host factor Mx1 and that mice can be rendered resistant to a virulent infection by "intracellular immunization" achieved through germline transformation. PMID- 2194674 TI - Inhibition of purified p21ras farnesyl:protein transferase by Cys-AAX tetrapeptides. AB - We report the identification, purification, and characterization of a farnesyl:protein transferase that transfers the farnesyl moiety from farnesyl pyrophosphate to a cysteine in p21ras proteins. The enzyme was purified approximately 60,000-fold from rat brain cytosol through use of a chromatography step based on the enzyme's ability to bind to a hexapeptide containing the consensus sequence (Cys-AAX) for farnesylation. The purified enzyme migrated on gel filtration chromatography with an apparent molecular weight of 70,000 100,000. High resolution SDS-polyacrylamide gels showed two closely spaced approximately 50 kd protein bands in the final preparation. The enzyme was inhibited competitively by peptides as short as 4 residues that contained the Cys AAX motif. These peptides acted as alternative substrates that competed with p21H ras for farnesylation. Effective peptides included the COOH-terminal sequences of all known p21ras proteins as well as those of lamin A and B. PMID- 2194675 TI - Interphase nuclear envelope lamins form a discontinuous network that interacts with only a fraction of the chromatin in the nuclear periphery. AB - Antibodies directed against nuclear envelope lamin proteins have been used in conjunction with three-dimensional light and electron microscope methodologies to determine the spatial organization of lamins in diploid interphase nuclei and to relate this organization to the positions of chromatin in the nuclear periphery. Using Drosophila early embryos, Drosophila Kc cells, and human HeLa cells, it is qualitatively and quantitatively observed that lamins are organized as a highly discontinuous, apparently fibrillar network that leaves large voids in the nuclear periphery containing little or no lamin. Using fluorescence microscopy to compare and quantitate the relationship between chromatin and the lamin network, it is found that although there is a strong tendency for the most peripheral chromatin to be positioned directly underneath a lamin fiber, only a small fraction of the chromatin in the nuclear periphery is sufficiently close to a lamin fiber to possibly be in direct contact. PMID- 2194676 TI - Human red cell glucose-6-phosphate dehydrogenase is encoded only on the X chromosome. PMID- 2194677 TI - Effects of cytokines on human thymic epithelial cells in culture. II. Recombinant IL 1 stimulates thymic epithelial cells to produce IL6 and GM-CSF. AB - Our earlier study reported the ability of interleukin 1 (IL1) to promote proliferation and to induce morphological changes of human thymic epithelial cells (TEC) in culture. The present study was undertaken to examine the effects of IL1 on the secretory function of TEC. Both human recombinant IL1 alpha and IL1 beta induced TEC to produce molecules in the culture supernatant fluids (TES) which displayed marked thymocyte proliferative capacities. This activity was specifically induced by IL1 since other TEC growth factors such as epidermal growth factor and a bovine pituitary extract had no effect on promoting secretion of T cell-activating molecules by TEC. Using specific radioimmunoassays for both forms of IL1, we found that unstimulated TEC produced negligible amounts of IL1 alpha and IL1 beta in TES, which were not increased by IL1 stimulation, and we concluded that the IL1-induced TES molecules were not IL1. IL1 induced TEC to produce IL6, as detected by the hybridoma growth factor biological activity. Neutralizing anti-IL6 antibodies completely blocked the thymocyte activating capacities of the IL1-induced TES thus implying a major role for IL6 in TEC derived T cell activation. IL1 also induced TEC to produce GM-CSF as measured by bioassay and confirmed by an immunoenzymetric assay. Our results confirm that TEC are a source of cytokines and show that TEC respond to IL1 by producing cytokines with consequences on the thymic lymphoid population. This further emphasizes the importance and complexity of paracrine molecular interactions involved in intrathymic development. PMID- 2194678 TI - Identification of a novel thymocyte growth-promoting factor derived from B cell lymphomas. AB - We found a unique thymocyte growth-promoting activity in supernatants (SN) from subclones of the B cell lymphoma CH12.LX. We have tentatively named this activity B-TCGF (for B cell-derived T cell growth factor) and characterized the activity produced by the CH12.LX.4866 subclone. This SN did not induce thymocyte proliferation alone, however, it enhanced both adult and fetal (Day 15 of gestation) murine thymocyte proliferation in the presence of IL-2, IL-4, or IL-7. Other known cytokines were screened for a B-TCGF-like activity using both adult and fetal thymocytes. IL-6 was found to be active only on adult thymocytes, while TNF alpha and GM-CSF were found to be active only on fetal thymocytes. However, neutralizing antibodies against these cytokines did not block the B-TCGF activity present in CH12.LX.4866 using either adult or fetal thymocytes. These observations suggest that the B-TCGF activity is mediated by a novel factor(s). The apparent molecular weight of this novel molecule(s) was 27-50 kDa determined by sizing HPLC. PMID- 2194679 TI - A novel surface antigen expressed by mature and activated rabbit T-lymphocytes. AB - The monoclonal antibody (Mab) 93C6 was used to identify a surface molecule expressed by mature and activated rabbit T-lymphocytes. This antigen was virtually absent in cells of the thymus (5% positive cells). All 93C6-positive cells expressed the rabbit pan-T marker L11-135 and proliferated in response to concanavalin A (Con A). When lymphocytes were activated in the presence of Con A, the expression of the 93C6 molecule was quantitatively increased. Con A stimulation alone did not markedly enhance expression of this antigen by thymocytes, but stimulation with both Con A and interleukin-2 (IL-2) resulted in a population of thymocytes that expressed the antigen in a manner quantitatively similar to that of mature T-cells in other tissues. PMID- 2194680 TI - Diversity among tubulin subunits: toward what functional end? PMID- 2194681 TI - Increasing tubC beta-tubulin synthesis by placing it under the control of a benA beta-tubulin upstream sequence causes a reduction in benA beta-tubulin level but has no effect on microtubule function. AB - We have constructed a chimeric beta-tubulin gene that places the structural gene for the tubC beta-tubulin of Aspergillus nidulans under the control of the benA beta-tubulin promoter. Introduction of either this chimeric gene or a second wild type benA gene into a benomyl-resistant benA22 strain causes it to become benomyl sensitive, indicating that the introduced genes are functional. Analysis of the tubulin proteins synthesized in benA22 strains into which a second wild-type benA beta-tubulin gene was transformed showed that the total amount of beta-tubulin protein was the same as in the parental strain with a single benA gene. Thus the level of beta-tubulin must be regulated. This was also true of transformants carrying an extra copy of the chimeric beta-tubulin gene. The total amount of beta-tubulin was the same as in the parental strain. Two-dimensional gel analysis showed that the endogenous benA22 and the introduced chimeric tubC gene contributed equally to the total beta-tubulin pool. The fact that one-half of the benA beta-tubulin could be replaced by tubC beta-tubulin with no effect on the growth of the cells suggests that the benA and tubC beta-tubulins are functionally interchangeable. PMID- 2194682 TI - [Computers in psychiatry]. AB - The author provides information on a discussion of "Computers in psychiatry" at a nation--wide gathering of psychiatrists. He deals of computers in psychiatry and submits suggestions ensuing from the discussion. PMID- 2194683 TI - [History of psychiatric facilities in the Silesian region in the 19th century]. AB - A historiographic paper in which the authors--psychiatrists--deal, based on research in archives, with the period preceding by approximately 100 years the opening of the psychiatric sanatorium in Opava. The beginnings of institutional care of the mentally sick in the Silesion region were in 1841 and were associated with the construction of an "asylum" on the grounds of the newly built hospital in Opava, a small house for 20-24 patients kept under inhuman conditions. An advance was the provisional arrangement involving the lease of a castle in Albrechtice for 36 and finally 90 patients in 1873. The regulations of the institute and rules of behaviour of the keepers were already on an advanced level of psychiatric in-patients care. The concept of the Opava sanatorium was according to documents in the archives elaborated by the 51-year-old Dr. Franz Kostl, one of the founders of Prague psychiatric institutions. His project has been preserved. The Opava sanatorium was opened and work started on March 29, 1889. PMID- 2194685 TI - [Advances in studies on traditional Chinese medicine and Western medicine treatment of viral myocarditis]. PMID- 2194684 TI - [Psychiatric rehabilitation]. AB - The author presents a brief account of the development of psychiatric rehabilitation during the past two centuries. He draws attention to new trends in rehabilitation of the mentally sick during the post-war period and at present. He describes the system of rehabilitation in the Soviet Union which began to develop as a results of efforts in the Bekhterev Institute in Leningrad. In our country the law on social security in 1964 created conditions for protected workshop and protected work places. In 1973 methodical instructions of the Ministry of Labour and Social Affairs issued instructions which specified the principles of planning, establishment and operation of these facilities. At the end of 1986 the Ministry of Health CSR issued an amendment to the concept of psychiatry which contains the organization of psychiatric rehabilitation not only in in-patient but in particular in out-patient psychiatric facilities. PMID- 2194686 TI - Epidemiology, prevention and control of legionellosis: memorandum from a WHO meeting. AB - This Memorandum describes the following aspects of legionellosis: clinical presentations of legionella infection, general epidemiology (including nosocomial outbreaks and travel-associated legionnaires' disease), surveillance and reporting of cases, the organism and its environment, and measures for prevention and control. These topics were discussed by experts at a meeting in Geneva on 27 29 November 1989. This article also includes their conclusions and recommendations for research in critical areas including surveillance and preventive activities that have been found to be effective. PMID- 2194687 TI - Randomized trial of sulfamethoxazole + trimethoprim versus procaine penicillin for the outpatient treatment of childhood pneumonia in Zimbabwe. AB - Reported are the results of a randomized trial of sulfamethoxazole + trimethoprim versus procaine penicillin for the outpatient treatment of pneumonia in 614 children aged 3 months to 12 years at primary health care clinics in Chitungwiza, a large town near Harare, Zimbabwe. Diagnosis and treatment were carried out by nurses, without medical supervision. The presence of lower respiratory tract infection that required antibiotics was diagnosed on the basis of a recent history of a cough and the presence of a respiratory rate of greater than 50 per minute. Patients were followed up by a research nurse with minimal drop-out losses. Referred children were examined and assessed by a doctor at the Chitungwiza General Hospital. Of the study children, 65 (11%) were referred to hospital, but only 8 (1.3%) had pneumonia that required a change in the treatment (5 in the sulfamethoxazole + trimethoprim group and 3 in the procaine penicillin group). There were no significant differences in outcome between the two treatment groups. One child, who had evidence of infection with human immunodeficiency virus (HIV), died. Sulfamethoxazole + trimethoprim and procaine penicillin were highly and equally effective for the outpatient treatment of children who had been clinically diagnosed to have pneumonia by primary health care workers. PMID- 2194688 TI - Newly transmitted Plasmodium falciparum malaria in the central highland plateaux of Madagascar: assessment of clinical impact in a rural community. AB - Plasmodium falciparum has recently reappeared in the central highland plateaux of Madagascar. To define its role in the overall malaria pathology occurring during the rainy season, we conducted a clinical and parasitological study among the 2776 consultants of a malaria field health centre which we established in the middle of the transmission area. From January to June 1988 the overall parasite rate was 63.2% and did not vary with age; the overall splenic rate was 46.9%, decreasing in individuals over 15 years of age. After the beginning of the main transmission season, an increase in parasite rates and parasite densities was observed, while febrile illnesses associated with malaria parasitaemia decreased. During the second part of the rainy season the parasite densities started to decrease, while parasite rates and malaria-associated fevers remained at the same level. The frequency of fevers was not related to the malaria parasite density owing to individual and seasonal variations. PMID- 2194690 TI - Detection of moving flow separation in pulsatile flow and the degree of stenosis by power of Doppler shift signals. AB - Power ratios were derived from the principle of ultrasonic Doppler velocimetry to determine a ratio of the volume of vortices to the total vessel volume under the ultrasonic beam. This ratio also equals the ratio of the cross-sectional area of vortices to the vessel lumen. In vitro pulsatile flow experiments were performed in a Reynolds number range of 1,230-4,320 with axisymmetric constrictions with area reductions of 55%, 65%, 70%, and 85% to model carotid stenosis. Flow separation downstream from the model stenoses was detected, and the power ratio fluctuated when vortices with the forward- and reverse-flow velocity components passed by the measurement position. The power ratio estimated the degree of stenosis within 10% of error. Ensemble average of the power ratio was computed to obtain the statistically averaged separated flow region. The moving flow reattachment point was revealed downstream from the 85% stenosis at a Reynolds number of 900. PMID- 2194689 TI - International travel and HIV infection. AB - Although human immunodeficiency virus (HIV) infection is a worldwide problem, its prevalence and pattern vary from country to country. Accordingly, the risk to international travellers of acquiring HIV infection also varies widely in different parts of the world, and depends principally on their behaviour. The risk of sexual acquisition of HIV infection can be virtually eliminated by avoiding penetrative sexual intercourse with intravenous drug users and persons who have had multiple sexual partners (such as prostitutes) or reduced by the use of condoms. The risk of parenteral exposure to HIV can be reduced by avoiding parenteral drug use and behaviour that is likely to lead to injury (with its attendant risk of requiring blood transfusion) and by seeking medical facilities with adequate capabilities to screen blood donors for HIV and to sterilize instruments. HIV screening of international travellers is an ineffective, costly, and impractical public health strategy for limiting the worldwide spread of HIV infection. Travellers infected with HIV require specialized advice regarding health precautions, prophylactic medications, and immunization. PMID- 2194691 TI - [Free amino acid and synthesis of polyamines in Plasmodium-berghei-infected RBC]. AB - The contents of free amino acids and the activity of ornithine decarboxylase in infected RBC of chloroquine-sensitive strain of Plasmodium berghei(CS) were similar to those in chloroquine-resistant strain (CR). After treatment with chloroquine (10mg/kg im) no effect on the formation of free amino acids was found after 20th, but chloroquine (5mg/kg im) inhibited the enzymatic activity of the CS RBC by 79.6% whereas that of the CR by 55.7%. The contents of spermidine in CS and CR infected RBC were found to be 139 +/- 27 and 528 +/- 140 nmol/10(9) infected respectively. Cycloleucine inhibited the formation of spermidine by 44% in CS and 57% in CR groups, while co-administration of methionine (100mg/kg) with cycloleucine (80mg/kg) could reverse the inhibitory effect and raise the contents of spermidine to 294 +/- 56 and 657 +/- 129 nmol/10(9) infected RBC in CS and CR groups respectively. This indicates that methionine had significant effect on the formation of spermidine in CS strain, but there was still a remarkable difference, when compared with CR strain. It is suggested that the activities of S-adenosyl-methionine synthetase and other enzymes involved in polyamine formation might be the causal factors. PMID- 2194692 TI - [Analysis on mixed distribution of tertian malaria with long and short incubation]. AB - The purpose of this paper is to make an epidemiological analysis of the mixed distribution of tertian malaria with long and short incubation by mathematical model. Using the Gram-Charlier series and the Marquardt's nonlinear least square dissecting method and the systematic computerized program for the dissection of mixed samples of tertian malaria with different incubation periods over the past 7 years in Changde City, Hunan Province, and discussing the influence of the climatic factor and epidemic process, it has been inferred that there were two kinds of incubation period of tertian malaria in this city. The long incubation period cases and the short ones have formed seasonal excessive distributions during the late spring and during the summer and autumn, respectively. The parameters estimated from the model had an optimal goodness of fitting to practical distribution (P = 0.9967). According to the tests for initial data the model was demonstrated to be effective as there was no statistically significant difference between the theoretical and the actual values. PMID- 2194693 TI - [Changes in bile composition in rabbits infected with Clonorchis sinensis]. AB - This article presents the changes in the concentration of bilirubin, cholesterol, phospholipid, bile acid and the activity of bacterial beta-glucuronidase in hepatic bile of rabbits infected with metacercariae of Clonorchis sinensis. We found that the activity of bacterial beta-glucuronidase was significantly higher in the infected group (52.6 +/- 31.6 u/dl) than that in control rabbits (12.5 +/- 20.5 u/dl) (P less than 0.001), and no marked changes in the concentration of bilirubin, cholesterol, phospholipid and bile acid were found. concentration of bilirubin, cholesterol, phospholipid and bile acid were found. By using alcian blue-PAS combined stain method the authors also noticed that the amount of glycoprotein in goblet cells has considerably increased and secreted increasingly to the biliary duct after infection with Clonorchis sinensis. As the increase in bacterial beta-glucuronidase activity and glycoprotein in bile is in favour of the formation of pigment stone, this may explain why clonorchiasis is often complicated with cholelithiasis. PMID- 2194694 TI - Antiplatelet treatment with ticlopidine in unstable angina. A controlled multicenter clinical trial. The Studio della Ticlopidina nell'Angina Instabile Group. AB - We conducted a controlled multicenter trial with central randomization and evaluation of events under blind conditions involving 652 patients with unstable angina. Patients were treated either with conventional therapy alone (group C) (n = 338) or with conventional therapy combined with an inhibitor of platelet aggregation, ticlopidine 250 mg b.i.d. (group C + T) (n = 314). Patients were assigned randomly within 48 hours of admission and followed up for 6 months. With the "intention-to-treat" approach, the primary end points, vascular death and nonfatal myocardial infarction, were observed in 13.6% of the patients in group C and in 7.3% of the patients in group C + T, which is a reduction in risk of 46.3% (p = 0.009). Vascular mortality was 4.7% in patients in group C and 2.5% in patients in group C + T, which is a reduction in risk of 46.8% (p = 0.139). The risk of nonfatal myocardial infarction was reduced by 46.1% (p = 0.039), with a frequency of 8.9% in patients in group C and 4.8% in patients in group C + T. New Q wave myocardial infarction occurred with a frequency of 6.8% in patients in group C and 3.8% in patients in group C + T, which is a reduction in risk of 44.1% (p = 0.091). Fatal and nonfatal myocardial infarction was 10.9% in patients in group C and 5.1% in patients in group C + T, which is a reduction in risk of 53.2% (p = 0.006). These findings confirm the importance of platelets in the pathogenesis of unstable angina and the usefulness of antiplatelet treatment for the prevention of cardiovascular events. PMID- 2194695 TI - Threshold concentrations of endothelin-1 potentiate contractions to norepinephrine and serotonin in human arteries. A new mechanism of vasospasm? AB - Endothelin-1 is an endothelium-derived vasoconstrictor peptide. Its circulating levels are below those known to evoke direct vascular effects. To study whether low concentrations of endothelin-1 potentiate the effects of other vasoconstrictor hormones, we suspended isolated human internal mammary and left anterior descending coronary artery rings in organ chambers for isometric tension recording. In mammary artery rings, the contractions to norepinephrine (3 x 10( 8) M) were potentiated by threshold (3 x 10(-10) M) and low concentrations (10( 9) M) of endothelin-1 (96 +/- 35% and 149 +/- 58% increase from control; p less than 0.01 and 0.001; n = 6). The inhibitor of endothelial nitric oxide formation L-NG-monomethyl arginine did not affect the potentiating effects of the peptide. The calcium antagonist darodipine (10(-7) M) prevented the potentiation of the response to norepinephrine evoked by endothelin-1. Similarly, contractions to serotonin (10(-7) or 3 x 10(-8) M) were amplified by endothelin-1 (3 x 10(-10) M) in the mammary (30 +/- 9%) and in the coronary arteries (59 +/- 25%). Endothelin 1 (10(-9) M) further potentiated the response (57 +/- 23% in mammary and 87 +/- 26% in coronary arteries; p less than 0.05; n = 7 and 3). The sensitivity of mammary arteries to calcium chloride was markedly enhanced in the presence of endothelin-1 (3 x 10(-10) M; concentration shift, eightfold; p less than 0.01; n = 5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2194696 TI - 5-year incidence of atherosclerotic vascular disease in relation to general risk factors, insulin level, and abnormalities in lipoprotein composition in non insulin-dependent diabetic and nondiabetic subjects. AB - The 5-year incidence of myocardial infarction and claudication was examined in a group of middle-aged patients (n = 133, 70 men and 63 women) with newly diagnosed non-insulin-dependent diabetes and nondiabetic control subjects (n = 144, 62 men and 82 women). The effects of general risk factors, plasma insulin level, and lipoprotein abnormalities on the incidence of myocardial infarction and claudication were also evaluated by univariate analyses in both diabetic patients and nondiabetic subjects and by multivariate analyses combining both groups. The age-adjusted incidence of myocardial infarction was higher both in diabetic men (19.4%) and diabetic women (11.0%) than in nondiabetic men (3.2%, p = 0.009) and nondiabetic women (3.0%, p = 0.047). Similarly, the age-adjusted incidence of claudication was higher among the diabetic patients (20.3% vs. 8.0% for men, p = 0.06; 21.8% vs. 4.2% for women, p = 0.003). None of the general risk factors (i.e., low density lipoprotein [LDL] cholesterol, blood pressure, smoking, and high density lipoprotein [HDL] cholesterol) showed an association with the risk of myocardial infarction either in the diabetic or nondiabetic groups of subjects, but an ischemic electrocardiographic abnormality at the baseline examination predicted myocardial infarction in diabetic men. In univariate analyses in diabetic subjects, high serum total cholesterol, low HDL cholesterol, high very low density lipoprotein (VLDL) cholesterol, and high total, LDL and VLDL triglycerides, and in nondiabetic subjects, high VLDL cholesterol and LDL triglycerides were associated with the appearance of claudication. In multivariate analyses including both diabetic and control subjects, only diabetes had an independent association with myocardial infarction, whereas smoking, high LDL triglycerides or VLDL cholesterol, and high fasting plasma insulin showed independent relations to claudication. The present results indicate that changes in lipoprotein composition characteristic of non-insulin-dependent diabetes are atherogenic and increase the risk of atherosclerotic vascular disease. Furthermore, high plasma insulin might also be involved in atherogenesis, independent of lipoprotein abnormalities. PMID- 2194697 TI - Toward a new understanding of the mechanism and prevention of sudden death in coronary heart disease. PMID- 2194698 TI - The academic life cycle of a noninvasive test. PMID- 2194699 TI - Turning back group A streptococci. PMID- 2194700 TI - Aging and risks for dehydration. AB - The elderly are at increased risk for dehydration and associated fluid and electrolyte imbalances. Changes in functional and mental status, medication effects, and changes in the aging renal system all may be factors. Furthermore, hypodipsia, or insensibility to thirst, may be a physiologic process of aging. These and other risk factors are presented, along with a guide to the management of dehydration in the elderly. PMID- 2194701 TI - Evaluation of wheezing in the nonasthmatic patient. AB - Wheezing is a nonspecific manifestation of airway obstruction. Even though bronchial asthma is the most common cause of wheezing, a variety of pulmonary and nonpulmonary conditions can present with this symptom. In recent years methacholine provocation challenge has simplified detection of bronchial asthma; however, establishing accurate diagnosis of other causes of wheezing is important because each condition requires specific treatment. This article describes a methodical approach to the diagnosis of wheezing in patients who are not asthmatic. PMID- 2194702 TI - Thrombotic thrombocytopenic purpura in a patient with AIDS. AB - Thrombotic thrombocytopenic purpura (TTP) has only recently been documented in association with human immunodeficiency virus infection. The authors present the clinical, laboratory, and pathologic features of a unique case of secondary thrombotic thrombocytopenic purpura occurring in a patient with AIDS, including the immunohistologic characterization of the vascular thrombi. They also review 12 previously reported cases of thrombotic thrombocytopenic purpura associated with human immunodeficiency virus infection. PMID- 2194703 TI - Carbamazepine-induced dyskinesia and ophthalmoplegia. AB - Antiepileptic drug-induced dyskinesias are well described with phenytoin but have only occasionally been reported with carbamazepine. We present two patients with carbamazepine-induced dyskinesia, one with ocular skew deviation and down-beating nystagmus associated with a high therapeutic level, and another with systemic dyskinesia with a toxic carbamazepine level, and compare these with previously reported cases. PMID- 2194704 TI - Tight blood glucose control: is it worth it? AB - Several investigations have assessed the relationship between glycemic control and complications in diabetes mellitus. Key evidence is reviewed that supports the beneficial effects of "tight" blood glucose control. Pertinent animal data show that good blood glucose control is associated with less retinopathy and nephropathy and fewer congenital anomalies in offspring. Short-term studies in humans show similar trends in microvascular complications and pregnancy. Similarly, peripheral neuropathy may be lessened with lower blood glucose. Although no studies have demonstrated a reduction in atherosclerotic disease with improved glycemic control, dyslipidosis frequently improves, which should reduce the risk for coronary heart and peripheral vascular disease. PMID- 2194705 TI - Intra/extra-amniotic administration of prostaglandin F2a in fetal death, missed and therapeutic abortions. AB - Prostaglandin F2a was used for termination of pregnancy in two groups of patients. The first included eighteen patients with either missed abortion or intrauterine fetal death, and were treated by intrauterine-extraamniotic infusion of 20 mg prostaglandin F2a. The treatment was successful in 14 patients (mean induction-abortion interval 6.7 hours). Four patients, where the above method failed to induce labor, were given intravenously prostaglandin F2a or oxytocin simultaneously or separately; the expulsion time ranged from 12 to 48 hours. The second group included twelve patients who underwent a therapeutic abortion following either a diagnosis of fetal congenital abnormality or because of a maternal indication. The therapeutic abortion was performed using prostaglandin F2a (25-40 mg) via amniocentesis. The treatment was successful in all patients (mean induction-delivery interval 10.6 hours). PMID- 2194706 TI - The role of tumour markers in ovarian cancer. AB - In the present review, the Authors have evaluated the current status of the utilization of the principle tumor markers for ovarian carcinoma in clinical gynecological practice. The major difficulty in individualizing a single marker is represented by the histological differentiation of the tumor itself. In fact, whereas for the malignant germ cell tumors, useful markers (AFP, B-HCG) are already available, for other histological forms, valid markers have been identified only because of the availability of the monoclonal antibody: CA 125. Even if this marker cannot be proposed for mass screening, it represents a useful instrument for the diagnosis and monitoring of ovarian carcinoma. The serum levels are well correlated with the clinical status of the patient and high concentrations of the marker are strongly indicative of disease progression at the second-look. Numerous other markers such as NB 70K, IAP, PLAP, CA 15-3 and TAG 72, are actually in the clinical evaluation phase, for the most part in association with CA 125. PMID- 2194707 TI - Ovarian bilateral cystic teratomas: diagnosis and therapy in a young woman. AB - A case of ovarian bilateral cystic teratomas is described in young women. Difficult problems concerning diagnosis and therapy are deeply analyzed because of the rarity of this case. Bilateral and typical ultrasound aspects appear strongly indicative of an ovarian tumor. A conservative reproduction-preserving procedure was performed, due to the young age of the patients. PMID- 2194708 TI - Restless legs syndrome in pregnancy. Case reports. AB - Restless legs syndrome is a common complaint in pregnancy affecting up to one in every three women. The exact pathophysiology is poorly understood. The majority of patients respond to simple explanation and reassurance, however, a small proportion may suffer debilitating symptoms requiring drug therapy. We describe two such cases. PMID- 2194709 TI - Monthly cosmic activity and pregnancy induced hypertension. AB - Monthly distribution of PIH (Pregnancy Induced Hypertension) was investigated in relation to the number of deliveries and nine specific cosmic and geomagnetic activity parameters during the years 1979-1983. PIH was observed in 3.165% of 19,843 deliveries. Significant (p less than 0.01) inverse correlation between the PIH index and monthly geomagnetic activity level was shown. Moderately significant (p less than 0.05) correlation with monthly maximal (noon hours) gamma-radiowave propagation was evident as was inverse correlation with this parameter in hours of minimal (early morning) propagation. PMID- 2194710 TI - Creutzfeldt-Jakob disease with periodic lateralized discharge: case report. AB - A case of CJD with PLD in the first EEG is reported. The PLD became bilateral in the next EEG. The subsequent EEGs showed shifting asymmetries. In this case, PSD reappeared after 5 months' absence. The PLD occasionally appeared over the hemisphere ipsilateral to the side of the myoclonic jerks. The clinical significance of the PLD and reappearance of PD, and the diagnostic importance of PLD are discussed. PMID- 2194711 TI - Correlation of orbital computed tomography and antibodies in patients with hyperthyroid Graves' disease. AB - The purpose of this study was to elucidate the incidence of orbital changes in computed tomography, and the relationships of orbital changes with eye-muscle antibody (EMAb), thyrotrophin-binding inhibitor immunoglobulin (TBII), antithyroglobulin antibody (TgAb) and anti-thyroid microsomal antibody (MsAb), in 55 consecutive patients with hyperthyroid Graves' disease. EMAb was demonstrated by an immunoperoxidase technique. The results showed that the prevalence of orbital fat increase, extraocular muscle enlargement, lacrimal gland enlargement and optic nerve swelling were 54.5, 41.8, 21.8 and 16.5% respectively. There were 32.7% of patients without any orbital changes. The patients with extraocular muscle enlargement, lacrimal gland enlargement and optic nerve swelling had higher titres of EMAb than the patients without these orbital changes. The patients with lacrimal gland enlargement had a lower TBII index than those without. There was no difference in TgAb or MsAb between the patients with extraocular muscle enlargement, lacrimal gland enlargement, optic nerve swelling or orbital fat increase and those patients without these orbital changes. The patients with extraocular muscle enlargement, optic nerve swelling and orbital fat increase had a higher degree of exophthalmos than the patients without these orbital changes. EMAb was negatively correlated with TBII. However, there was no correlation between EMAb and TgAb or MsAb. The degree of exophthalmos was positively correlated with EMAb and negatively correlated with age. There was no correlation between exophthalmos and TBII, TgAb or MsAb. In conclusion, although the pathogenesis of orbital changes and hyperthyroidism is different, a close link between these two entities is suggested by the high incidence of orbital changes in hyperthyroid Graves' disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2194712 TI - Impaired prolactin secretion and body fat distribution in obesity. AB - Human obesity shows clustering within families. The hypothesis for the presence of a major gene or genes acting in human obesity is supported by recent evidence from studies of obesity in adoptees and their biological parents and siblings. The heterogeneity of obesity may be demonstrated by the shape of fat distribution and the prolactin response to insulin hypoglycaemia. Fat distribution has been shown to have a genetic background whereas a primary disorder of hypothalamic function is suspected in obese women who show an impaired prolactin response to insulin-induced hypoglycaemia. We have investigated the possible association between fat distribution and hypothalamic function in 23 extremely obese, nondiabetic premenopausal women who have been characterized using their absolute body weight, body mass index (BMI), fat distribution (expressed as waist to hip ratio), fasting insulin, basal prolactin and prolactin response to hypoglycaemia. Fasting insulin values showed a significant correlation (P less than 0.05, R = 0.604) with increasing waist to hip ratio (upper body segment obesity), whereas the graded prolactin response to hypoglycaemia of the obese women showed a negative association with increasing upper body segment obesity (P less than 0.05; R = -0.446). No relationship was observed between fasting insulin and the prolactin response to hypoglycaemia. We suggest that this previously unrecognized association of an impaired prolactin response to hypoglycaemia and upper body segment fatness may be useful for the investigation of the genetics of obesity. PMID- 2194713 TI - Characterization of Candida albicans epidermolytic proteases and their role in yeast-cell adherence to keratinocytes. AB - Epidermolytic proteases were partially purified from six strains of Candida albicans, four of which were isolated from patients with cutaneous diseases. Two of the strains exhibited a unique time-course of enzyme production compared to that previously reported, with detectable epidermolytic protease levels being significantly delayed. All epidermolytic proteases had pH and temperature optima of 4-4.5 and 35-37 degrees C, respectively. These conditions are consistent with the microenvironment of human skin, a habitat where an epidermolytic protease would appear to be an important advantage to the yeast. Candida epidermolytic proteases were more active against a substrate of normal human epidermis than that obtained from psoriatic patients. When human epidermis replaced bovine serum albumin as the protein source within the culture medium, the epidermolytic activity of the resultant enzyme was reduced by 9 and 25% for normal and psoriatic epidermis substrates, respectively. The proteases were found to contain major protein bands at 42 and 66 kDa. The ability of these same Candida strains to adhere to human epidermal cells was studied and found to be optimal at 35-37 degrees C within neutral pH values. Pepstatin, bovine brain gangliosides, and convalescent human serum all interfered with the adherence of the yeast to epidermal cells. A higher yeast-epidermal-cell adherence for Candida was demonstrated on normal rather than psoriatic epidermal cells, and after treating the cells with partially purified Candida protease. PMID- 2194714 TI - Assessment of disease severity and outcome in the gravitational syndrome using pulsed A-scan ultrasound to measure skin thickness. AB - In order to investigate the prognostic significance of skin thickening in the gravitational syndrome, 54 patients and 10 normal control subjects were studied. Patients were investigated using a standard questionnaire, as well as recording the results of clinical history and a physical examination. To quantify the severity of the syndrome, an index of disease severity was devised on the basis of the clinical findings. Skin thickness was measured using pulsed A-scan ultrasound on standardized sites on the lower leg in patients and controls. The results indicated that skin thickness determined non-invasively by pulsed A-scan ultrasound can be used to provide prognostic information in the gravitational syndrome. PMID- 2194715 TI - A comparative double-blind study of terbinafine (Lamisil) and griseofulvin in tinea corporis and tinea cruris. AB - In a double-blind randomized study, 92 patients with culturally proven tinea corporis and/or tinea cruris were treated orally with either terbinafine (Lamisil) (125 mg b.i.d.) or griseofulvin (500 mg b.i.d.) for up to 6 weeks. The two groups of patients and distribution of the target lesions were similar, but the analysis of the clinical scores showed that the terbinafine group had slightly higher mean scores at baseline (P = 0.186). At the end of therapy the proportion of patients with negative microscopy and culture was 78% in the terbinafine group and 83% in the griseofulvin-treated group. At the assessment 8 weeks after the end of therapy the percentages of terbinafine- and griseofulvin treated patients with negative mycology were 93 and 95%, respectively. There were three relapses after mycological cure in the griseofulvin group (8%) and two in the terbinafine group (4%). Griseofulvin-treated patients were treated for shorter periods than terbinafine-treated patients (i.e. 58% compared to 26% received only 2-4 weeks of therapy). In terms of overall effectiveness, there were no significant differences between the two treatments. Thirty-seven terbinafine patients (77%) compared to 36 griseofulvin patients (82%) had overall effective therapy. Eight terbinafine patients (16%) compared to 10 griseofulvin patients (20%) experienced at least one adverse event. Five patients in the terbinafine group and six in the griseofulvin group had to stop the treatment due to headaches or gastrointestinal disorders. One terbinafine patient had an elevation of liver function tests after 6 weeks of treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2194716 TI - Psittacosis presenting with erythema-marginatum-like lesions--a case report and a historical review. AB - A 14-year-old boy with psittacosis who developed skin lesions consistent with erythema marginatum is reported. This association has not been described previously. PMID- 2194718 TI - Are antiarrhythmic drugs safe? AB - The indications for antiarrhythmic therapy are far from clearly defined and the choice of treatment is usually based on empiric strategies. Antiarrhythmic agents can have serious side effects. Systemic adverse effects are usually use-related and reversible with withdrawal of the drug. Impairment of left ventricular function is considerable in patients with heart failure. The most important, life threatening side effect of antiarrhythmic drugs is their proarrhythmic tendency which gives rise to certain concern about their clinical use. Aggravation of arrhythmia often occurs without symptoms, goes unrecognized by the patient, and is exposed only by monitoring, exercise testing, or invasive electrophysiological testing. Patient monitoring with electrolyte measurement, Holter recording, and electrophysiological reassessment can reveal or reduce the proarrhythmic risk but cannot eliminate the problem completely. The institution of antiarrhythmic therapy should be considered in highly symptomatic or life-threatening arrhythmias after careful consideration of the benefit-risk ratio. PMID- 2194717 TI - Balloon aortic valvuloplasty in children. AB - The technique of balloon aortic valvuloplasty has been used in infants, children, and adults since its first description in 1983. Immediate results reported by several workers and intermediate-term results by a few workers appear encouraging. Complications are minimal although potential for arterial complications and aortic insufficiency should be recognized. Significant restenosis rates at intermediate-term follow-up have been reported and could be minimized by reducing the risk factors associated with recurrence. Echo-Doppler studies are useful in follow-up evaluation of balloon valvuloplasty. The results seem to compare favorably with those following surgical valvotomy. The indications are essentially the same as those used for surgery; a gradient in excess of 80 mmHg irrespective of symptoms or a gradient greater than or equal to 50 mmHg with symptoms or ST-T wave changes. Previous surgical valvotomy is not a contraindication for balloon valvuloplasty. The technique is applicable to subaortic membranous stenosis as well. Thus far only one- to two-year follow-up results are available. Five- to ten-year follow-up results to document long-term effectiveness of balloon aortic valvuloplasty are needed. Miniaturization of currently bulky dilating catheter systems and improving rapidity of inflation/deflation of balloons are necessary to increase safety and effectiveness of these techniques in infants and children. Meticulous attention to the details of the technique and further refinement of the procedure may further increase effectiveness and reduce the complication rate. PMID- 2194719 TI - Profiles in cardiology. Edward F. Bland. PMID- 2194720 TI - Group A streptococcal pharyngeal carriage, pharyngitis, and impetigo in two northern Canadian native communities. AB - The prevalence of pharyngeal carriage of group A streptococci, streptococcal pharyngitis, and impetigo was determined in schoolchildren in two northern communities, one Inuit (mean number of schoolchildren surveyed, 233) and one native Indian (mean number of schoolchildren surveyed, 349). At three surveys from November 1984 to May 1985, pharyngeal group A streptococcal carriage was 5.3%, 22%, and 34% in the Inuit community and 5.3%, 5.1% and 10% in the native Indian, with impetigo prevalence 1.6%, 3.8% and 1.0%, and 2.4%, 4.2% and 0.6%, respectively. Increased pharyngeal carriage correlated with the increasing number of household residents and the lower school grade. In 12 months of observation the incidence of group A streptococcal pharyngitis was 49/100 schoolchildren for the Inuit and 9.4/100 for the native Indian community, with impetigo 13/100 and 11/100 respectively. The maximal incidence of pharyngitis was late winter in the Inuit community and midsummer in the native Indian. The incidence of impetigo peaked in January for both communities. M and T typing showed consecutive outbreaks of different serotypes in the Inuit community, but a persistent low level of endemic infection in the Indian community. These observations suggest a seasonal prevalence of group A streptococcal pharyngeal carriage consistent with other North American populations, but marked inter-community variation in pharyngeal carriage and disease. The midwinter peak of impetigo appears unique to these populations. PMID- 2194721 TI - Recurrent posttraumatic dislocation of the hip. A report of two cases and review of the literature. AB - Posttraumatic recurrent posterior hip dislocations were observed in two adult patients. In neither case was there evidence of acetabular dysplasia, paralysis, or infection. In both cases the only significant abnormality discovered was a marked posterior capsular redundancy. In the second case this was clearly shown by a computed tomography (CT) arthrogram. In both instances plication of the posterior capsule prevented further dislocations; however, the second patient developed massive heterotopic ossification around the involved joint and osteonecrosis of the femoral head. Investigation with CT arthrography of patients sustaining one or more dislocations in response to minimal trauma aids in evaluation of capsular abnormalities that may be surgically correctable. PMID- 2194722 TI - The Judet quadricepsplasty for management of severe posttraumatic extension contracture of the knee. A report of a bilateral case and review of the literature. AB - Extension contracture of the knee is an increasingly recognized complication of severe femur fracture. Traditional management by Thompson quadricepsplasty may result in a variable return of knee flexion and the possibility of significant extension lag. The Judet technique of quadricepsplasty offers the advantages of a controlled, sequential release of the components limiting knee flexion and a reduced potential for iatrogenic quadriceps rupture or extension lag. Judet quadricepsplasty corrected severe bilateral extension contractures with excellent results at 17 months postoperatively in a 29-year-old man. PMID- 2194723 TI - Periosteal chondroma. A report of ten cases and review of the literature. AB - Periosteal chondroma is a slow-growing benign cartilaginous tumor of limited size arising within or under the periosteum, which, through constant pressure, induces cortical erosion and periosteal reaction. Ten new cases of periosteal chondroma are reported. All were treated by marginal or intralesional excision. No local recurrence was seen following this treatment. These patients demonstrated the clinical, roentgenographic, and pathologic features of this benign entity, which aid diagnosis, thereby avoiding overtreatment. PMID- 2194724 TI - Completely displaced supracondylar fracture of the humerus in children. A review of 1708 comparable cases. AB - The displaced supracondylar fracture of the humerus in children is a very difficult injury to treat. Manipulation and splint immobilization is perhaps the most common method. A review of the literature on 1708 comparable cases revealed that several different treatments were used. The worst results occurred with manipulation and splint immobilization alone. The best results occurred with traction techniques and well-performed Kirschner-pin transfixation, either open or closed. Complications such as Volkmann's ischemic contracture and myositis ossificans are rare. A completely displaced supracondylar fracture in a child should not be treated by manipulation and splint immobilization alone. PMID- 2194725 TI - New advances and concepts in amputee management after treatment for bone and soft tissue sarcomas. AB - Amputation is still necessary to achieve disease-free margins in some patients with osteogenic sarcoma. Improving the quality of life for this largely young patient population has become increasingly important considering the dramatic increase in their survival rate. A multidisciplinary approach should include prosthetic devices that are comfortable and lightweight, and produce an energy efficient gait, an aggressive postoperative rehabilitation, and an objective evaluation of progress. This approach will help improve the high net energy expenditure of ambulation and the asymmetrical stance time experienced by this group of individuals and allow them to gain equal status in society. PMID- 2194726 TI - Immediate care of crush injuries and compartment syndromes with the split thickness skin excision. AB - Prospective evaluation of the one-stage procedure in 32 patients who suffered from 37 severe friction-avulsion injuries was carried out. Most injuries (81%) were in the lower extremity. Split-thickness skin excision was used for immediate diagnosis of flap vascularity and wound coverage. Split-thickness skin was harvested from the avulsed flap surfaces after they were temporarily sutured back to their original bed. Dermal capillary bleeding served as an indicator for tissue viability, thus delineating a clear line for debridement. All compartments were decompressed, and debridement of all devascularized tissues was performed. Most fractures were fixed with interfragmentary screws and external fixators. Viable parts of the avulsed flaps were sutured back to their original bed and exposed bones were covered with transposed muscles. Skin defects were grafted with the split-thickness skin that was harvested in the first stage and was meshed 1:3 to allow drainage. Most patients (26 out of 32) had only one surgical procedure for their extensive injuries. The split-thickness skin excision is effective in the establishment of debridement borders and helps in saving maximal viable flap area (49.4%). All wounds healed with no major wound complications. The split-thickness skin excision can be used immediately in the care of severe crush injuries, compartment syndromes, and open fractures as a one-stage procedure with the following advantages: (1) reliable diagnosis of flap vascularity, (2) immediate wound coverage with the possibility of drainage, (3) elimination of further debridements procedures, (4) elimination of distant skin donor wounds, and (5) less hospitalization. PMID- 2194727 TI - Femoral anteversion in adolescents and adults measured by ultrasound. AB - Femoral anteversion (AV) was determined by ultrasound in 40 adolescent and adult patients with rotational disorders of the femur, and the results were compared with AV measurements by biplanar roentgenography. With the patients supine, their knees flexed 90 degrees, and their lower legs strapped in the vertical position, one scan only of the proximal femur was needed to measure the anteversion by ultrasound. The transducer was tilted until the desired measuring line appeared horizontal on the monitor screen. The angle of tilt of the transducer, which represented the AV angle, was measured with an attached clinometer. The correlation between ultrasound and roentgenographic AV angles was high, indicating that reliable results were obtained by ultrasound. The preferred reference line was the head-trochanter tangent, which is recommended for clinical use. Consistently greater AV values were measured by ultrasound than by roentgenography. Thus, 10 degrees should be subtracted from the ultrasound values in order to obtain the real AV angles. One of the benefits of ultrasound is the elimination of radiation hazards to the patients. Ultrasound is recommended as a screening technique for patients with rotational disorders of the femur. PMID- 2194728 TI - Growth-plate chondrocyte cultures for reimplantation into growth-plate defects in sheep. Characterization of cultures. AB - Damage to epiphyseal growth plates due to fracture, trauma, or infection can lead to invasion of bone across the cartilage and localized arrest of long-bone growth. The implantation of a viable de novo cartilage plug into such defects may provide the appropriate cartilage presence necessary to inhibit the initial formation of bony bridges across the epiphysis and so maintain the growth potential. De novo cartilage plugs were prepared from ovine growth plates by culturing isolated epiphyseal chondrocytes from fetal lambs. After 14 days of culture, these de novo cartilage discs were composed of chondroitin sulfate, a small amount (5%) of dermatan sulfate, and cartilage-specific collagen. The cellular morphology and the histochemistry resembled resting zones of normal growth-plate cartilage. Those de novo cartilage discs, which had been embedded in gelled Type I collagen, retained their morphology and could be easily manipulated. On the other hand, Type II collagen and a polyuronic acid gauze (Surgicel) were not satisfactory substrates to facilitate subsequent transplantation into growth-plate defects. The use of 5-carboxyfluorescein diacetate succinimidyl ester (CSFE) throughout the cultures of epiphyseal chondrocytes or prolonged incorporation of [3H]-thymidine appeared to label the cells with useful markers for following their fate subsequent to implantation in vivo. PMID- 2194729 TI - Surgical cases and observations. Amputation at the ankle-joint. 1843. PMID- 2194730 TI - Feedback in myoelectric prostheses. AB - This article briefly reviews the history of the use of feedback in artificial limbs. It suggests that researchers have concentrated unduly upon the use of feedback to control prehensile force or joint angle and advocates a broader perspective. In that context, the article presents a comprehensive view of the need for feedback in myoelectric prostheses. The difficulties of designing transducers to meet the stringent demands of prosthetics applications are considered, and problems inherent in several alternatives are identified. Various means of conveying feedback information to the amputee are reviewed in some detail. The concept of feedback in control systems is introduced in the context of closed-loop control of a prosthesis. The surprisingly good performance of skilled users of myoelectric prostheses is noteworthy implying that the distinction between sensory and proprioceptive feedback may be somewhat artificial. By integrating these two feedback types a satisfactory feedback system may become an attainable goal. PMID- 2194731 TI - New developments in recreational prostheses and adaptive devices for the amputee. AB - Regardless of age, conventional prostheses and traditional rehabilitation programs no longer meet the needs and expectations of active amputees. The emphasis on fitness, the availability of stronger and lighter materials, and strong consumer demand have led to plethora of new prosthetic designs by progressive prosthetists and engineers. Prosthetic training techniques now take into account the amputee's recreational and sports needs and desires, using advanced athletic training concepts to achieve superior performance in a wide variety of activities. The surgeon, as a key member of the amputee team, should be aware of these profound changes so that they may contribute his or her skill in surgically crafting an optimally functional residual limb. This will allow the amputee to reach for the maximum in cardiopulmonary fitness while achieving social reintegration after amputation. The combination of skills, concepts, and techniques of the amputation surgeon, prosthetist, and therapist/trainer has led to a unique situation, in which for the first time, amputees are able to successfully compete in sports because of their prostheses, rather than in spite of them. PMID- 2194732 TI - Limb salvage versus amputation. Preliminary results of the Mangled Extremity Severity Score. AB - Objective criteria can predict amputation after lower-extremity trauma. The authors examined the hypothesis that objective data, available early in the evaluation of patients with severe skeletal/soft-tissue injuries of the lower extremity with vascular compromise, might discriminate the salvageable from the unsalvageable limbs. The Mangled Extremity Severity Score (MESS) was developed by reviewing 25 trauma victims with 26 severe lower-extremity open fractures with vascular compromise. The four significant criteria (with increasing points for worsening prognosis) were skeletal/soft-tissue injury, limb ischemia, shock, and patient age. (There was a significant difference in the mean MESS scores; 4.88 in 17 limbs salvaged and 9.11 in nine limbs amputated; p less than 0.01). This scoring system was then prospectively evaluated in 26 lower-extremity open fractures with vascular injury over a 12-month period at two trauma centers. Again, there was a significant difference in the mean MESS scores; 4.00 for the 14 salvaged limbs and 8.83 for the 12 amputated limbs (p less than 0.01). In both the prospective and retrospective studies, a MESS score of greater than or equal to 7 had a 100% predictable value for amputation. This relatively simple, readily available scoring system of objective criteria was highly accurate in acutely discriminating between limbs that were salvageable and those that were unsalvageable and better managed by primary amputation. PMID- 2194733 TI - The measurement and visualisation of vessel blood flow by magnetic resonance imaging. PMID- 2194734 TI - Reproducibility of ultrasound attenuation measurements in bone. PMID- 2194735 TI - Ultrasound velocity in bone. PMID- 2194736 TI - Timing iron dextran doses when plasmapheresis is required. PMID- 2194737 TI - ASHP therapeutic guidelines on nonsurgical antimicrobial prophylaxis. ASHP Commission on Therapeutics. PMID- 2194738 TI - Selecting drug therapy for patients with duodenal ulcers. PMID- 2194739 TI - Effects of experience and motivation on symmetrical-maze performance in the prairie vole (Microtus ochrogaster). AB - Sex differences in spatial skills are sometimes attributed to sex differences in spatial experience. This hypothesis rests on two assumptions: Spatial experience typically differs with sex and spatial experience has lasting effects on spatial cognition. We tested the latter assumption in a controlled experiment with wild caught prairie voles (Microtus ochrogaster) and their spatially deprived, laboratory-reared, first-generation offspring; we found the assumption to be unjustified. Although major differences in spatial experience had no effect on maze performance, relatively small differences in motivation produced a significant difference in error rates. PMID- 2194740 TI - Relaxin. AB - 1. Relaxin is a hormone of reproduction that appears to affect parturition, uterine accommodation, and sperm motility to varying degrees in many species. 2. All relaxins have the same two chain, disulfide-linked insulin-like structure and two arginine residues in the midregion of the B chain. 3. The active relaxin molecule is produced by excision of a connecting peptide from the prohormone. 4. The biosynthetic pathways of insulin and relaxin are alike, but the relaxin prohormone is about twice as large as the corresponding proinsulin. 5. The primary structures of relaxins from apparently closely related species differ significantly in their amino acid compositions and do not fit into the traditional scheme of molecular evolution. PMID- 2194741 TI - A computerized respiratory sinus arrhythmia program for the non-invasive assessment of parasympathetic activity. AB - The availability of sophisticated signal analysis methods based on the use of micro-computers allows an accurate non-invasive assessment of parasympathetic activity, through the measurement of the respiratory sinus arrhythmia. The program described herein is in Quickbasic and consists of 5 programs. At termination of the computer analysis the results are printed which include the average heart rate for inspiration and expiration, the averaged standard deviation of the R-R intervals for inspiration and expiration, and the R-R interval in milliseconds averaged for all inspiratory and expiratory cycles. Significant correlations were obtained when comparing the analyses of the computerized program with a manual method. PMID- 2194742 TI - A review on biomedical image processing and future trends. AB - The last two decades have witnessed a revolutionary development in the field of biomedical and diagnostic imaging. Imaging procedures and modalities which were only in the experimental research phase in the early part of the last two decades, have now become universally accepted clinical procedures. They include computerized tomography (CT), magnetic resonance imaging, ultrasound imaging, nuclear medicine imaging, computerized hematological cell analysis, etc. In the past, the conventional and relatively simple image processing techniques such as image enhancement, gray-level mapping, spectral analysis, region extraction, etc. have been modified for biomedical images and successfully applied for processing and analysis. The role of image enhancement, gray-level mapping, and image reconstruction from projections algorithms in CT and other radiological imaging modalities is well evident. Recently, many advances in biomedical image processing, analysis, and understanding algorithms have shown a great potential for enhancing and interpreting useful diagnostic information from these images more accurately. This paper presents a review on the current state-of-the-art techniques in biomedical image processing and comments on future trends. PMID- 2194743 TI - Some aspects of treatment of coliform mastitis. PMID- 2194744 TI - Antibiotic treatment of infectious bovine keratoconjunctivitis. PMID- 2194745 TI - Hormonal changes in brain dead patients. AB - Thirty neurologically impaired (Glasgow Coma Score less than 7) patients were evaluated to determine if changes in serum levels of thyroid hormone, cortisol, insulin, or lactate suggest that replacement therapy is needed before removal of organs for donation. Serum levels of free thyroxine (fT4), thyroid-stimulating hormone (TSH), reverse T3 (rT3), cortisol, insulin, and lactate were monitored in 16 patients before and after brain death and in 14 additional patients who were similarly compromised but did not become brain dead. Low fT3, normal fT4, and normal or high rT3 as found in most patients were consistent with a variant of the euthyroid sick syndrome although TSH was elevated in some patients. Cortisol, insulin, and lactate levels were also normal or high. No correlation was found between low thyroid hormones and elevated lactate or the amount of vasopressor needed to sustain BP. No significant changes occurred in hormone or lactate levels after brain death. The explanation for an elevated lactate remains unclear but we do not believe this single finding justifies the diagnosis of a hypothyroid state in these patients or the administration of thyroid hormone to brain dead organ donors. PMID- 2194746 TI - Cardiovascular changes in infants with beta-hemolytic streptococcus sepsis. AB - Sequential hemodynamic and biochemical changes were studied in 24 infants with sepsis due to beta-hemolytic streptococcus to define the temporal patterns of physiologic events and to compare them in surviving (n = 11) and nonsurviving (n = 13) infants. Septicemia was documented by positive blood culture in all. Biophysical and biochemical measurements were obtained before and hourly, for 11 h after antibiotic therapy was initiated. Surviving infants had significantly higher Hct and systolic and mean arterial pressures than nonsurvivors. In nonsurvivors, low BP was associated with a concomitant rise in CVP and severe metabolic acidosis refractory to therapy. Although there were no differences in PaO2 or PaCO2 between survivors and nonsurvivors, arterial-alveolar oxygen gradients were significantly greater in nonsurviving infants. These data show cardiorespiratory and metabolic alterations that differentiate surviving and nonsurviving infants with beta-hemolytic streptococcal septicemia. PMID- 2194747 TI - Pulmonary dysfunction after cerebral injury. AB - Pulmonary dysfunction is a common complication of severe head injury. The degree of initial hypoxemia which develops appears to correspond with the location and magnitude of the head injury. If unrecognized and not aggressively treated, the hypoxic insult will magnify the cerebral insult. A severe postinjury hypermetabolic state also develops and, if unrecognized and not managed aggressively with nutritional support, can also lead to severe catabolism, increased infection, and further lung dysfunction. Although supportive care is the major treatment at present, pharmacologic manipulation of the increased catecholamine activity, which is considered to be causative, may be effective in controlling both the impaired gas exchange and the hypermetabolic state. A knowledge of the various lung dysfunction states which occur in the head-injured patient population is required to optimize recovery and minimize complications. PMID- 2194749 TI - Instrumentation for estimating pulmonary function in patients on positive end expiratory pressure. PMID- 2194748 TI - Reversal of cardiogenic shock and asystole in a septic patient with hypertrophic cardiomyopathy on verapamil. PMID- 2194750 TI - Head and neck squamous cancers. AB - Head and neck squamous cancers are a heterogeneous group of neoplasms with varying etiologic factors, presenting symptoms, staging, treatment, and expected outcome. In this monograph, we discuss principles of management common to all sites as well as individual differences. The presenting symptoms of disease are reviewed, stressing the importance of early diagnosis. Accurate pathologic diagnosis can be improved on in difficult cases by newer immunohistochemical techniques. Following diagnosis, accurate clinical staging must be performed, and the evaluation of an unknown primary in the neck is described. We review general considerations for planning the treatment of head and neck cancer, and then discuss specific guidelines for individual sites, stressing the optimal integration of surgery and radiation therapy, particularly brachytherapy. Controversial management issues and new, innovative approaches are discussed. The conventional use of chemotherapy in head and neck cancer is for palliation of recurrent disease. In recent years, chemotherapy has been added to the primary treatment program in an induction role, as a radiosensitizer, as an adjunct following standard therapy, and for organ preservation. The current status of these roles is reviewed. This is a cancer for which there are known etiologic agents. Future efforts in this disease should be directed toward early detection and prevention. PMID- 2194752 TI - Current controversies in nutrition. PMID- 2194751 TI - Catheter balloon valvuloplasty in adults, Part I: Aortic stenosis. PMID- 2194753 TI - Reactive astrocytes--a review. AB - This review provides an historical and current perspective on astrocytes in the CNS, detailing their morphological and biochemical diversity, origins and transformation to reactive astrocytes in experimental lesions and clinical disease states which result in gliosis. Recent studies on reactive astrocytes have been facilitated by the availability of immunocytochemical probes for GFAP and other distinctive cellular components. The effects in vitro of 'growth factors' on astrocytic transformation are briefly considered. An understanding of astrocytic transformation has implications for neural transplantation. PMID- 2194754 TI - [Shockwave therapy of gallstones--indications and results]. PMID- 2194755 TI - [Methods and results of gallstone dissolution]. PMID- 2194756 TI - [Pathophysiology of the formation of gallstone recurrences]. PMID- 2194757 TI - [Choice of procedure in Kuntscher nailing. A look backward--current status- perspectives]. PMID- 2194758 TI - [Tendon rupture in chronic kidney insufficiency--"uremic tendonopathy"? A literature-supported documentation of 3 cases]. AB - This is a report on three cases with spontaneous ruptures of major tendons of the lower extremities. In two cases ruptures occurred in the quadriceps tendon, one of them bilaterally, and in one case in the Achilles' tendon. All patients suffered from chronic renal failure and were treated by long-term hemodialysis. Coincidentally secondary hyperparathyroidism was noticed twice. The pathophysiological relation between chronic renal failure and spontaneous tendon rupture is still unknown. An "uremic tendopathy" is discussed. PMID- 2194759 TI - [The necessity of intraoperative identification of the contralateral lobe in "struma uninodosa"]. AB - Between July 1st, 1988 and July 31st, 1989 we registered 74 consecutive patients with a unilateral goitre. In all these patients the preoperative sonography showed no pathologic finding in the contralateral lobe of the thyroid. In 16 cases we found and resected nodules in the lobe, which was supposed to be normal. A consequent exposure of the whole thyroid gland, independent of the preoperative sonographic finding, principally is necessary. So, the rate of "false" goitre recurrences might be decreased. PMID- 2194760 TI - [Spontaneous bacterial peritonitis in adults. Case observations of deficient infection immunity in ascites]. PMID- 2194761 TI - [The history of intramedullary nailing. A brief look backwards]. PMID- 2194762 TI - [Oligohydramnios]. PMID- 2194763 TI - [Prediction of ovulation]. AB - Prediction of ovulation was carried out by B-ultrasonography, BBT graph, cervical mucus and appearance of mittelschmerz in 45 normally menstruation women for a total of 72 cycles. LH peak values were also determined in 20 cases (20 cycles). The results were as follows: 1. The relation-ship between each index and ovulation: (1) The ultrasound image of follicle: average daily follicular growth during the 4-5 day before ovulation was 2.5 +/- 2.1 mm (means +/- s). Average diameter of the biggest follicles one day before ovulation was 20.6 +/- 2.0 mm. (2) The change of cervical mucus: the opening of external os and the secretion of mucus with ferning became most typical one day before the ovulation. (3) BBT graph: in a majority of cycles, ovulation occurred at the first day of the initial rise in temperature. (4) Mittelschmerz: occurred in 35% of cycles and appeared within 24 hours before ovulation. (5) LH peak value: ovulation occurred 24 to 48 hours after the first significant rise of LH, and within 24 hours after LH peak value. 2. The relation-ship between indices: in the majority of cases, when we employ the ultrasound image of follicular rupture as a signs of ovulation, LH peak value, follicle of biggest diameter, maximum volume of cervical mucus, the lowest point of BBT and mittelschmerz appear on the same day, namely, one day before ovulation. The authors suggest that ultrasonography used combination with other parameters provides a feasible and relatively accurate and reliable method for the prediction of ovulation in clinical practice. PMID- 2194764 TI - [Magnetic resonance imaging in the diagnosis of intervertebral disk diseases]. PMID- 2194765 TI - [Percutaneous radiofrequency coagulation in the treatment of trigeminal neuralgia using a new trigeminal nerve stereoguide]. AB - The authors designed a new stereotactic frame for percutaneous radiofrequency coagulation in treatment of tic douloureux. During operation it is fixed on patient's skull with three screws. The position of the foramen ovale is calculated from lateral and axial radiogram and defined with X, Y and Z coordinates. Then the radiologic electrode can be introduced from the cheek through the foramen ovale to the Gasserion ganglion and the retroganglionary rootlets. After thermo-coagulation at 70 degrees-75 degrees c, for 2-3 minutes, 42 patients had good effect immediately. There was no complication. The follow-up time varied from 6-19 months (average 13 months). Pain recurrence were found in two cases (4.7%). PMID- 2194766 TI - [Cellular biological study of giant cell tumor of bone: a 10-year summary]. AB - This article is a summary of the main research accomplishments on giant cell tumor of bone (GCT) carried out in this laboratory in the past ten years. The stromal cells (STC) in GCT have long been regarded as a single neoplastic element. By means of immunological method they are segregated into EA rosette forming cells (RFC) and non-rosette-forming cells (NRFC). It is herein demonstrated that RFC are macrophages of the defensive mechanism, while NRFC bear the hallmarks of neoplastic cells. The views concerning the nature of the multinucleated giant cells (MGC) so far remains controversial. One of the authors, on the basis of the survival time in thin vitro culture, classifies them into short survival MGC (S-MGC) and long survival MGC (L-MGC). Immunological and cytochemical evidences indicate that S-MGC are similar to osteoblasts and foreign body giant cells and express macrophage antigen. Moreover, macrophages in GCT can actually form MGC. L-MGC, however, present characteristics of neoplastic cells which are known to be able to form tumor giant cells. Thus the concept of GCT has been renovated. Evaluation of the aggressiveness of GCT is important and challenging, as the Jaffe grading system is no longer widely considered valid. In our laboratory this problem has been approached by cytomorphometry, nuclear DNA cytometry and multifactor analysis techniques. Parameters which are conducive to predicting the prognosis of GCT are found, which would render help to clinical diagnosis and research of this semimalignant tumor. PMID- 2194767 TI - Testing nicotine gum for ulcerative colitis patients. Experience with single patient trials. AB - Epidemiologic studies have documented an association between nonsmoking and ulcerative colitis and case reports have demonstrated that symptoms improve with smoking and worsen with removal of a nicotine source. A double-blind randomized crossover trial for individual ulcerative colitis patients (single-patient trial, or N of 1 clinical trial) was designed to study the safety, patient acceptance, and the effectiveness of nicotine gum in improving patient symptoms and proctoscopic appearance of involved colon. Seven nonsmoking patients chewed up to 10 squares/day (20 mg) of nicotine gum or placebo gum for two weeks. Therapy was crossed-over every two weeks over the eight-week trial. Effectiveness was judged from comparisons between nicotine-gum and placebo-gum periods of patient self reported symptoms at the conclusion of each two-week period using visual analog scales and proctoscopic appearance using ordered categorical scales. Three of seven patients, all three of whom were former smokers, demonstrated sufficient improvement without adverse effects to warrant institution of nicotine gum into their drug treatment regimens. Three patients demonstrated an uncertain response, despite tolerating the drug, and have not had nicotine gum added to their regimens. One patient could not tolerate the medication and was withdrawn from the study. No serious side effects were noted. We conclude that a randomized trial for an individual patient is a useful method for evaluating treatment regimens for ulcerative colitis and that nicotine gum may be effective therapy for individual patients with ulcerative colitis who demonstrate an objective response with few adverse effects. PMID- 2194768 TI - Effects of alcohol on lectin binding affinity in rat gastric mucosa. AB - Fluoresceinated lectins were employed to qualitatively evaluate cell surface carbohydrates, with and without ethanol exposure, in rat stomach mucosae. Rats received 1 ml of saline, or 50% or 100% ethanol orally. After 30 min, tissue samples of the glandular stomach were retrieved, cryosectioned, and incubated with one of a panel of lectins. Another set of sections was preincubated with neuraminidase to remove sialic acid residues. Qualitative evaluation of lectin binding showed that although several different sites stained, concanavalin A was the only lectin to stain the extracellular matrix, and soybean agglutinin the only lectin to stain chief cells. Neuraminidase preincubation enhanced lectin binding to both stained and previously unstained sites. Ethanol, both 50% and 100%, produced changes in both neuraminidase-treated and untreated tissues, increasing the specific binding of concanavalin A, Ulex europaeus agglutinin I, and wheat germ agglutinin, while decreasing Helix pomatia agglutinin and soybean agglutinin. These results suggest that ethanol can, through unknown mechanisms, alter carbohydrate binding affinity. PMID- 2194769 TI - Amyloidosis complicating inflammatory bowel disease. A case report and review of the literature. PMID- 2194770 TI - Randomized, double-blind trial of midazolam and diazepam for endoscopic sedation in children. AB - We performed a prospective, randomized, double-blind study of 41 children (6-18 years of age) who were undergoing esophagogastroduodenoscopy (EGD) to compare the efficacy of diazepam and midazolam with respect to quality of sedation and amnesia. The endoscopist assessed the patients for control of salivation, gag reflex, vomiting and cooperation after intravenous injection of either 0.1-0.15 mg/kg of midazolam or 0.2-0.4 mg/kg of diazepam. The patients answered a questionnaire at 1 and 24 h after the procedure to assess recall of procedure details, pain and/or discomfort, and their medication choice for future procedures. Vital signs were monitored for 1 h after injection. Although midazolam caused greater mean maximum increase in heart rate than diazepam (30 vs. 14/min), no difference was found between the two treatment groups with respect to other vital signs. There was also no difference in physician's assessment or patient recall of specific events during the procedure. However, significantly fewer patients recalled pain or discomfort with midazolam at both 1 and 24 h following the procedure (p = 0.02). In addition, more patients receiving midazolam indicated preference for the same sedation for future procedures. We conclude that midazolam may provide better amnesia in children undergoing endoscopic procedures. PMID- 2194771 TI - Developing multisite research in critical care. AB - Conducting a clinical critical care research project simultaneously in a variety of institutions requires careful and comprehensive planning. The authors outline the steps in the planning and development of a multisite research project, stressing those areas requiring special attention and decision making. PMID- 2194772 TI - [Effect of hexamethylene bisacetamide on human gastric cancer cell line SGC 7901]. AB - After the human gastric cancer cells SGC-7901 were cultured with 5 mM hexamethylene bisacetamide (HMBA) for 120 hr, cell growth was inhibited. The doubling time increased from 48 hr in untreated cells to 99.6 hr in HMBA-treated cells. The maximal increase in growth was 2.4-fold as compared to 6.4-fold in the untreated control. 3H-thymidine incorporation was inhibited by HMBA and the colony formation rate was reduced. There was concomitant decrease in carcino embryonic antigen and beta-2 microglobulin as determined by radioimmuno-assay. Lactic dehydrogenase (LDH) and its isoenzyme assay revealed a marked increase in H-type LDH but the total enzyme activity was reduced. These results indicate that HMBA inhibits proliferation of SGC-7901 cells in vitro. PMID- 2194773 TI - [DNA-DNA hybridization and the phylogenetic relations in 2 genera of voles, Alticola and Clethrionomys (Microtinae: Rodentia)]. PMID- 2194774 TI - [The effect of earlier pregnancies on the prevalence of goiter and nodules in thyroid-healthy women]. AB - Ultrasound scans of the thyroid were performed in 106 women of mean age 41.9 (36 50) years, 53 with and 53 without a history of previous pregnancy, with the object of ascertaining the prevalence of goitre and thyroid nodules. Goitres (defined as a thyroid volume exceeding 18 ml) were found in 22 of the women with previous pregnancies (41.5%). Thyroid nodules were found in 23 of the 106 women (21.6%). Whereas only five of the 53 women without previous pregnancies (9.4%) had thyroid nodules, they were noted in 18 of the 53 women who had had children (33.9%), the difference being statistically significant (P less than 0.05). Thyroid cysts were found in 12 of the 106 women (11.3%), though there was no significant difference between the two groups. Thyroid calcification was noted in only one woman. The results highlight the consequences of iodine deficiency in a region where iodine intake is inadequate (Kiel) and show that the deficiency is accentuated during pregnancy. PMID- 2194775 TI - [The sonographic findings in splenic infarcts]. PMID- 2194776 TI - [Targetted hemotherapy with special reference to the cellular components]. PMID- 2194777 TI - [Conclusions from the outbreak of foot-and-mouth disease in the government district of Hannover in 1987/1988]. AB - Knosel und Tiroke (1989) reported recently experiences derived from the control of FMD outbreaks in 1987/88 in Lower Saxony (FRG). On the basis of the described facts and in connection with the observations of the other outbreaks during the last 20 years in the FRG several conclusions were drawn: (1) The compulsory annual vaccination was not able to prevent these outbreaks. (2) Hence follows that very probable introductions of FMD from foreign countries cannot be prevented, especially since such infections were due to infected swill fed to pigs, and those strains were normally not related to the vaccine strains used. (3) Considering all circumstances of the recent outbreaks, it seems unrealistic to believe the primary infection was not due to the escape of virus from the neighboring vaccine plant. (4) The annual vaccination campaigns since 1970 against FMD were useless because most of the primary outbreaks of FMD since then can be traced to the production or the application of vaccines. (5) The legislative control measures are not sufficient to prevent secondary outbreaks. It was recommended to extend the quarantine areas as well as the radius of ring vaccination and to prolong the period of quarantine. (6) The regulation of tremendous losses of trade is obscure because camouflage of the origin of infections blocks the application of the principle of ultimate responsibility. Facit: Eradication of the disease and strict prevention of its introduction into Europe should be the principal strategy of FMD control for the future instead of imperfect protecting one species of the susceptible animal population. PMID- 2194778 TI - Aetiology of diarrhoea in pre-term neonates at Kenyatta National Hospital nursery, Nairobi, Kenya. AB - The aetiology of two outbreaks of diarrhoea in pre-term neonates (March-August; September, 1987), at Kenyatta National Hospital was studied. The first outbreak involved 98 neonates and enteropathogenic E. coli of different serotypes were the most commonly isolated agents (54%), with serotype 086a:K61 dominating. These were followed by Salmonella (16%) also of different groups, and then rotavirus (6%). Two campylobacter and two Shigella were isolated from four individual neonates. Mixed infections were mainly those of Salmonella and E. coli (5 cases). E. coli serotype 086 was found to be in circulation throughout the study period (March-August, 1987), whilst 044:0125 and 0128 circulated for a limited period. Salmonella and some strains of E. coli caused persistent diarrhoea despite antibiotic therapy. Nosocomial infections were found to play a role in subsequent diarrhoeas. In the second diarrhoea outbreak, again enteropathogenic E. coli and Salmonella were the most frequently isolated. However, in this outbreak, there was no single E. coli serotype revealed that some possessed plasmids of 120-160 megadalton. However, a search for human immunodeficiency viral antibodies in 120 stools produced negative results. PMID- 2194779 TI - Cholelithiasis in the western region of Saudi Arabia. AB - This is a prospective study of 454 patients with cholelithiasis treated surgically in the University Hospital at Jeddah admitted to surgical department of K.A.U.H. from 1979 until the end of 1987. Biliary surgery constituted 4.7% of all major operations reviewed in our Hospital. The disease affected females 4.5 times more than males. Right hypochondrial pain was present in 74.2% of cases, biliary colic in 60% and obstructive jaundice occurred in 14.09% of patients. The clinical diagnosis of cholelithiasis was confirmed by radiological examinations by laboratory, oral and I.V. Cholangiogram, and Ultrasound. These included liver function tests. All cases had cholecystectomy. This was carried out electively in 95.34% of patients, and as an emergency in only 4.63% of cases. Exploration of the CBD was performed in 14.09% of patients. Choledochoduodenostomy in 0.44% and sphincterotomy. Sphincteroplasty in another 0.44% of cases. There was no operative mortality, and post op complications occurred in 14.53% of patients. PMID- 2194780 TI - Sequences of standard methods to test effects of chemicals on terrestrial arthropods. PMID- 2194781 TI - Environmental and health risks of hydroquinone. AB - Hazard assessment of hydroquinone has been evaluated from bibliographical and original data on the physicochemical properties, the environmental behavior, and the biological effects of this aromatic compound. Hydroquinone, which is produced in large amounts and widely used, must be considered as an environmental contaminant. However, it is not persistent. The ecotoxicity of this molecule, which must be linked to its physicochemical properties, varies from species to species. Its acute and chronic toxicity toward higher terrestrial organisms is moderate. Hydroquinone is estimated to be nonmutagenic by the Ames test but induces chromosome aberrations or karyotypic effects in eucaryotic cells. Carcinogenic and teratogenic potentials have been at present inadequately studied. The study underlines the complementarity of QSAR models and experimental approaches when an attempt is made to obtain ecotoxicological profiles of pollutants. PMID- 2194782 TI - Steroid receptor family: structure and functions. AB - Steroid receptors are a class of molecules that function as both signal transducers and transcription factors. From cloned sequences it is apparent that steroid receptors and other transcription factors belong to a superfamily of proteins that appear to function by similar mechanisms. Functional domains for hormone and DNA binding, and for transcriptional activation, have been defined for several receptors. In some cases, specific amino acids required for function have been identified. The multi-functional steroid receptor molecules are modular in nature in that domains function independently of structural position in receptor molecules and can even function after insertion into unrelated transactivation proteins. The mechanism of receptor action is complex and multistage and a number of unanswered questions remain to be defined. Receptors are inactive in the absence of hormone in vivo; the proposed components of this inactive complex include several proteins and RNA. Theories on the physiological role of HSP 90 in this complex range from an artifactual interaction to an absolute conformational requirement for hormone binding. Although its function has not been demonstrated clearly yet, there is a consensus that one major function is to inactivate receptor by blocking DNA binding. Most of the steroid receptors appear to be nuclear in the absence of hormone. The transformation process produces a receptor molecule that is capable of specific DNA binding and transcriptional activation. The specificity of DNA binding is conferred by as few as three amino acids in the first finger of the C1 region. Receptors appear to bind to DNA as dimers although whether dimers are preformed in cytoplasm remains unknown. Although the DNA binding domain is required for gene activation, other regions of the molecule in the carboxyl and amino terminus enhance activation function. Important interactions of steroid receptors with other receptors and unrelated transcription factors has been proposed and most certainly occurs. Finally, posttranslational modifications such as phosphorylation have been postulated to modulate several functional properties of steroid receptors. PMID- 2194783 TI - Endocrine treatment of breast cancer in women. PMID- 2194784 TI - The hormone-induced regulation of contact-dependent cell-cell communication by phosphorylation. AB - Although there is insufficient evidence to propose an elaborate paradigm for the regulation of connexon gating, a simple model emerges from results of studies done to date. Basically, this centers around the most consistent findings: namely, that activation of pkA has an enhancing effect on cell communication while activation of pkC decreases that process. This fits well the reported phenomena associated with gap junctions, particularly those involving growth control. For example growth factors, including tumor promoters which work via pkC, usually reduce cell-cell communication whereas agents that decrease growth often raise cellular cAMP levels, which can lead to increased communication. It can be argued that this model is too simple because it fails to take into account other intracellular agents that are thought to alter junctional gating: cytoplasmic acidification, cellular free Ca2+, tyrosine protein kinases, and tentatively, pkG. Proton and Ca2+ transporting systems are mainly activated by serine/threonine protein kinases such as pkA and pkC. Some ion channels are not regulated by phosphorylation but instead are modulated by other ions. However, at the moment there is no evidence as to which ion-specific channels mediate the changes in cellular pH or Ca2+ that cause a loss in communication. Neither is it known whether pH or Ca2+ levels are in vivo regulators of the junctions. This is especially so as fairly high levels of injected Ca2+ pass through the gap junctions of viable cells. The role of tyrosine protein kinases in connexon gating may involve interaction with the pkA and pkC regulatory cascades. For example, the pkA inhibitor protein (pkI) is 80-90% inactivated when tyrosine phosphorylated by the EGF receptor or pp50v-src (D. Walsh, personal communication). In this situation, activity of the C subunit of pkA could be enhanced, or the lifetime of its catalytic activity extended. In some systems, pp60v-src is known to activate the pkC pathway. Thus, tyrosine protein kinases may invoke pkA and pkC pathways; however, the amplitude of enzyme activation and the temporal kinetics of this process are unknown. The fact that gap junctions are regulated at the transcription level and probably at the protein level by protein kinases is of major interest. This is especially so as the only known molecular mechanism that gap junctional communication mediates is the activation of cAMP-dependent protein kinases by hormone-induced signals passed from receptor bearing cells to receptorless partners. PMID- 2194785 TI - Signal transduction mechanisms of Ca2+ mobilizing hormones: the case of gonadotropin-releasing hormone. AB - Multiple (at least seven) steps are involved in GnRH-induced gonadotropin secretion and gonadotropin gene expression. After binding to specific receptors located exclusively on pituitary gonadotrophs, GnRH stimulates a rapid phosphodiesteric hydrolysis of phosphoinositides for which no rise in [Ca2+]i is required. Activation of PLC is most likely mediated by a pertussis toxin insensitive GTP-binding protein (Gp). In its activated state (Gp-GTP) the binding affinity of GnRH to is receptor is reduced. Rapid formation of IP3 will enhance Ca2+ release from intracellular sources most likely via a specific IP3 receptor. The transient Ca2+ rise might be responsible for a burst phase of LH release lasting for about 100 sec, which is not dependent on extracellular Ca2+. The backbone moiety of the phosphoinositides, DG, and the elevated [Ca2+]i are most likely responsible for translocation of PKC subspecies from the cytosol to the membrane. The most likely candidates are alpha- and beta II-PKC. The activated PKC subspecies phosphorylate substrate proteins which activate secretory reactions and participate in gonadotropin gene expression. In parallel Ca2(+) influx via nifedipine-sensitive and insensitive channels further elevates [Ca2+]i, which participates in the sustained phase of gonadotropin secretion in concert with the activated PKCs. GnRH also triggers the release of AA and the formation of lipoxygenase and/or epoxygenase products of the fatty acid which are also involved in the process of the exocytosis. We predict that the continuous supply of DG and AA needed for GnRH action is also provided via activated PLD which will also supply phosphatidic acid, the role of which is as yet unclear. The interaction of the various second messengers involved in GnRH action (IP3, Ca2+, DG, AA) and their relative roles in gonadotropin secretion and gonadotropin gene expression await further investigation. In several aspects GnRH action on gonadotropin secretion is unique when compared to other Ca2(+)-mobilizing ligands: 1) At physiological concentrations GnRH up-regulates its own receptors whereas most ligands down-regulate the respective receptor; 2) PKC up-regulates GnRH receptors whereas in most cases PKC down-regulates the ligand receptor; 3) GnRH stimulation of PLC activity is most likely mediated by Gp whereas some Ca2(+)-mobilizing ligands operate via Gi; 4) Activated PKC does not exert negative feedback upon GnRH-induced inositol phosphate production as is the case with several other peptides; 5) Activated PKC might be responsible for Ca2+ influx whereas in several other systems PKC is inhibitory to Ca2+ influx.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2194786 TI - Thyroid-stimulating hormone: biosynthesis, cell biology, and bioactivity. PMID- 2194787 TI - Progesterone as a bone-trophic hormone. AB - Experimental, epidemiological, and clinical data indicate that progesterone is active in bone metabolism. Progesterone appears to act directly on bone by engaging an osteoblast receptor or indirectly through competition for a glucocorticoid osteoblast receptor. Progesterone seems to promote bone formation and/or increase bone turnover. It is possible, through estrogen-stimulated increased progesterone binding to the osteoblast receptor, that progesterone plays a role in the coupling of bone resorption with bone formation. A model of the interdependent actions of progesterone and estrogen on appropriately-"ready" cells in each bone multicellular unit can be tied into the integrated secretions of these hormones within the ovulatory cycle. Figure 5 is an illustration of this concept. It shows the phases of the bone remodeling cycle in parallel with temporal changes in gonadal steroids across a stylized ovulatory cycle. Increasing estrogen production before ovulation may reverse the resorption occurring in a "sensitive" bone multicellular unit while gonadal steroid levels are low at the time of menstrual flow. The bone remodeling unit would then be ready to begin a phase of formation as progesterone levels peaked in the midluteal phase. From this perspective, the normal ovulatory cycle looks like a natural bone-activating, coherence cycle. Critical analysis of the reviewed data indicate that progesterone meets the necessary criteria to play a causal role in mineral metabolism. This review provides the preliminary basis for further molecular, genetic, experimental, and clinical investigation of the role(s) of progesterone in bone remodeling. Much further data are needed about the interrelationships between gonadal steroids and the "life cycle" of bone. Feldman et al., however, may have been prophetic when he commented; "If this anti glucocorticoid effect of progesterone also holds true in bone, then postmenopausal osteoporosis may be, in part, a progesterone deficiency disease." PMID- 2194788 TI - Effect of fenugreek seeds on blood glucose and serum lipids in type I diabetes. AB - The effect of fenugreek seeds (Trigonella foenum graecum) on blood glucose and the serum lipid profile was evaluated in insulin-dependent (Type I) diabetic patients. Isocaloric diets with and without fenugreek were each given randomly for 10 d. Defatted fenugreek seed powder (100 g), divided into two equal doses, was incorporated into the diet and served during lunch and dinner. The fenugreek diet significantly reduced fasting blood sugar and improved the glucose tolerance test. There was a 54 per cent reduction in 24-h urinary glucose excretion. Serum total cholesterol, LDL and VLDL cholesterol and triglycerides were also significantly reduced. The HDL cholesterol fraction, however, remained unchanged. These results indicate the usefulness of fenugreek seeds in the management of diabetes. PMID- 2194789 TI - Autoradiography using storage phosphor technology. AB - We describe the application of photostimulable storage phosphor imaging plates to autoradiography of samples labeled with 32P, 14C and 35S. Imaging plates can detect a 32P-labeled sample at an exposure level of 1 disintegration/mm2, and 14C and 35S at 25 disintegrations/mm2. Compared to X-ray film, imaging plates offer increased sensitivity of 15- to 250-fold for 32P and 20- to 100-fold for 14C and 35S. Resolution is in the 0.3 mm range and is therefore suitable for any gel or blot application. PMID- 2194790 TI - Quantitative autoradiographic imaging using gas-counter technology. AB - Gas counters based on the multiwire proportional counter (MWPC) and multistep avalanche (MSA) technologies can combine the functions of imaging and quantitation (or assay) of radioactively labelled electrophoretograms and blots. Submillimeter spatial resolutions combined with good quantitation have been achieved for the most common beta-emitting radio labels. The current state of development of this technology is reviewed and assessments of the performance of these devices relative to the more traditional systems (X-ray film and the scintillation counter) presented. Particular attention is paid to the potential of these devices to enhance the productivity of the scanning of blots and the performance of assays. PMID- 2194791 TI - Electrophoresis and densitometry of serum and urine in the investigation and significance of monoclonal immunoglobulins. AB - About 15% of monoclonal components or paraproteins are associated with malignancy when detected by simple electrophoresis on cellulose acetate membranes or agarose gel followed by protein staining. More sensitive methods for detecting monoclonal components result in a lower frequency of association with recognisable underlying disease. The sensitivity is dependent on the system used. Isoelectric focusing is 10 to 40 times more sensitive than simple electrophoresis at detecting monoclonal components. Electrophoretically separated bands may be quantitated densitometrically and at the present time this is the most satisfactory method for measuring monoclonal component concentration. Immunochemical methods for quantitating monoclonal components are limited by failure to react in a similar manner to polyclonal standards and giving problems of antigen excess resulting both in falsely elevated and low results. Electrophoretic methods must always be used in conjunction with these. The normal polyclonal ratio of immunoglobulin kappa:lambda light chain is disturbed by the presence of a monoclonal component. In 260 patients with myeloma we found that serum electrophoresis alone detected 90% while a disturbance in the kappa:lambda ratio detected 98%. However, 50% of monoclonal components less than 3 g/L were missed. Log kappa:lambda ratio correlates well with the densitometric scan of monoclonal components, both in vitro and in patients being monitored for treatment response in myeloma. This approach may complement or even replace densitometry for this purpose in the future. PMID- 2194792 TI - The use of charge-coupled devices in the quantitative evaluation of images, on photographic film or membranes, obtained following electrophoretic separation of DNA fragments. AB - Charge-coupled devices can provide an excellent means for the quantification of DNA band images on membranes and photographic film. However, proper consideration must be given to important parameters such as signal-to-noise ratio and resolution, especially in applications which demand the use of large format media. When employed in the direct imaging of chemiluminescent blots, the charge coupled device can provide equal or better sensitivity than that obtained by indirect methods using film, with the additional advantages of wide dynamic range and freedom from the vagaries of film processing. PMID- 2194793 TI - Renin is sorted to the regulated secretory pathway in transfected PC12 cells by a mechanism which does not require expression of the pro-peptide. AB - The rat pheochromocytoma cell line PC12 targets secretory proteins into two distinct pathways. When DNA encoding human prorenin was transfected into PC12 cells, the protein was sorted into the regulated secretory pathway and released with similar kinetics to noradrenaline upon carbachol stimulation. To determine whether information for targeting prorenin lies within the pro-peptide we have transfected PC12 cells with a construct lacking the pro-peptide coding sequence. The transformed line secretes an apparently fully active enzyme and responds to carbachol stimulation with a rapid release of renin activity. We conclude that the pro-peptide of renin is not essential for targeting the protein to the regulated pathway in PC12 cells. PMID- 2194794 TI - An NMR study of anion binding to yeast phosphoglycerate kinase. AB - Anion binding to yeast phosphoglycerate kinase has been investigated using 1H-NMR spectroscopy. The use of anionic paramagnetic probes. [Cr(CN)6]3- and [Fe(CN)6]3 , has enabled the location of the primary anion binding site in the 'basic-patch' region of the amino-terminal domain. The anions interact most closely with Arg-65 and Arg-168. The binding of these and a variety of other anions to this site is directly competitive with the binding of the substrate, 3-phosphoglycerate. Binding of 3-phosphoglycerate and 1.3-bisphosphoglycerate is, however, stronger than expected on the basis of anionic charge and causes conformational changes in the protein not seen with any of the other simple spherical anions investigated. This must be part, at least, of the substrate specificity. Evidence for a secondary anion binding site involving the side chains of surface lysine residues is also presented. It is suggested that the primary anion site is responsible for the observed activation by anions at low concentrations while the secondary site leads to inhibition at higher anion concentrations. The kinetics fit these deductions and a scheme for kinase activity is presented. PMID- 2194795 TI - Differential biogenesis of photosystem-II in mesophyll and bundle-sheath cells of 'malic' enzyme NADP(+)-type C4 plants. A comparative protein and RNA analysis. AB - We have investigated the photosystem-II organization in differentiating-bundle sheath cells of the three malate dehydrogenase (oxaloacetate decarboxylating) (NADP+)-type C4 species maize, Sorghum and Pennisetum. Using a set of nine different antisera raised against individual subunits of photosystem-II, we demonstrate that photosystem-II components constitute a substantial part of the thylakoid membranes of young bundle-sheath chloroplasts. The abundance of subunits of the photosystem-II core, i.e. the 47-and 43-kDa chlorophyll-a-binding proteins, polypeptides D1 and D2, cytochrome b559, and the 34-kDa polypeptide, varies with the developmental state of the plant. However, the levels of the 23 kDa, 16-kDa and 10-kDa extrinsic polypeptides of the water-oxidation complex are drastically reduced in bundle-sheath chloroplasts of all three species analyzed, regardless of their state of differentiation. The reduction in protein abundance is also reflected at the transcript level: only traces of the nuclear-encoded mRNAs are found in differentiating bundle-sheath cells of Sorghum, suggesting that the transcription of these genes has been switched off. Our data are compatible with the idea that the water-oxidation complex is a prime site for initiating or maintaining the process leading to photosystem-II depletion during differentiation of bundle-sheath cells. PMID- 2194796 TI - Organization and complete nucleotide sequence of the core-histone-gene cluster of the annelid Platynereis dumerilii. AB - The arrangement of the core-histone genes, their transcriptional polarity and their nucleotide sequences have been determined for the polychaete annelid Platynereis dumerili. A clone containing the core-histone genes was isolated from a annelid genomic library constructed in the EMBL-4 phage vector, using a trout H3 genomic probe. This clone was found to contain two and a half repeats of a 6 kbp EcoRV fragment that contained one copy of each of the core-histone genes. The clusters are tandemly arrayed in the genome and the gene order within the core histone cluster does not vary. Absolutely no differences were found in the nucleotide sequences comprising the same part of two adjacent clusters (bases 225 to 2776 and bases 5821 to 8825). The number of copies of the cluster appeared to be high: approximately 660 copies/diploid cell, as also observed in sea urchins and amphibians. There are also some additional subtypes of histone gene organization: multimers of tandemly arrayed genes and isolated genes; these are present at a much lower copy number (an average of 40-50 copies/diploid genome). Two mRNAs (for H2B and H3) are transcribed from one DNA strand and the two other histone mRNAs (for H2A and H4) from the other strand as is the case for some insects and certain vertebrates. No H1-coding sequence has been found in the completely sequenced four-membered cluster. The organization of histone genes in P. dumerilii is similar to the clustering found in Caenorhabditis elegans but in this nematode worm several different types of organization are observed with a low copy number for each. PMID- 2194797 TI - GAP1, the general amino acid permease gene of Saccharomyces cerevisiae. Nucleotide sequence, protein similarity with the other bakers yeast amino acid permeases, and nitrogen catabolite repression. AB - In Saccharomyces cerevisiae, mutations at the GAP1 locus selectively abolish the activity of the general amino acid transport system. This permease catalyses active transport of apparently all biological amino acids across the plasma membrane. We have determined the nucleotide sequence of the GAP1 gene. The sequence contains an open reading frame of 601 codons corresponding to a polypeptide of Mr 65578. This polypeptide is strongly hydrophobic; it exhibits three potential glycosylation sites. Hydropathy analysis suggests 12 membrane spanning regions. The N-terminal domain is charged, it does not resemble hydrophobic signal sequences found in secreted proteins. Hence the GAP1 gene encodes a protein with characteristics typical of integral membrane proteins translocating ligants across cellular membranes. The deduced amino acid sequence of GAP1 protein presents strong similarities to those of the yeast arginine, histidine and proline permeases, suggesting a common evolutionary origin for these amino acid permeases. Nitrogen-source regulation of the GAP1 permease is believed to occur at two distinct levels, i.e. permease synthesis and permease activity [Grenson (1983) Eur. J. Biochem. 133, 135-139]. Northern analysis of GAP1-specific transcripts in wild-type and in mutant strains is in agreement with these views and indicates that nitrogen catabolite repression of GAP1 synthesis occurs at the RNA level. PMID- 2194798 TI - Phalloidin-induced accumulation of myosin in rat hepatocytes is caused by suppression of autolysosome formation. AB - Administration of phalloidin in vivo to rats causes marked changes in the distribution of actin and myosin in hepatocytes, which accompanies reduced bile flow. We have found that in hepatocytes treated with phalloidin for 3 and 7 days, cellular myosin content increased about 1.5-fold and 4.7-fold, respectively. In addition, total cell protein content and several marker enzyme activities were also elevated by 30-120% depending on the duration of phalloidin treatment. These observations allow us to speculate that phalloidin somehow elicits inhibition of cellular protein degradation, which results in the increase of these protein levels. To examine this possibility further, we analyzed leupeptin-induced density shift of phagolysosomes. In normal liver, the injection of leupeptin/E64c caused an increase in the density of both heterolysosomes and autolysosomes, due to retarded digestion of sequestered proteins as a result of the inhibition of lysosomal cathepsins. Accumulation, in these denser autolysosomes, of lactic dehydrogenase, pyruvate kinase, aldolase, and myosin was demonstrated by enzyme assays and immunoblot analysis. In the phalloidin-treated liver, the increase in the density of autolysosomes and the accumulation of above cytoplasmic enzymes were markedly inhibited. However, phalloidin did not affect the shift in the density of heterolysosomes. From these data, we concluded that autolysosome formation was specifically hindered in phalloidin-treated rat hepatocytes, which results in the reduction of autophagic protein degradation and eventual increase in intracellular protein levels. PMID- 2194799 TI - Form determination of the heads of bacteriophages. AB - The shape of the DNA-containing heads of many bacteriophages is not only determined by the properties of the protein subunits which build the shell (capsid) but also by the scaffolding core which is a transient structure of the prohead. The form-determining properties of the scaffolding proteins have been characterized by genetic methods based on conditional mutants and site-directed mutagenesis. The mechanism of form determination has been studied by in vitro assembly experiments. The theoretical background is discussed and different models for mechanisms of form determination are considered. Definitive decisions about the validity of a model is still limited by the difficulty of obtaining unambiguous answers on the stoichiometry and the fine structure of the scaffold because of their high instability. PMID- 2194800 TI - Protein-decorated micelle structure of sodium-dodecyl-sulfate--protein complexes as determined by neutron scattering. AB - The structure of the complex between sodium dodecyl sulfate (SDS) and a deuterated bifunctional enzyme, N-5'-phosphoribosylanthranilate isomerase/indole 3-glycerol-phosphate synthase (Mr 49,484), has been studied in dilute solution by small-angle neutron scattering. The complex nearly acquired its final size, as shown by molecular-sieve chromatography, at the chosen SDS concentration of 1.6 mM, which is slightly below the critical micelle concentration of 1.8 mM (at the ionic strength of 0.1 M). The 452 amino-acid residues of the bifunctional enzyme were combined with 216 detergent molecules. The complex was found to be composed of three protein-decorated SDS micelles of unequal size, connected by short flexible polypeptide segments. The largest of the three micelles was the middle one. The SDS-protein complex contained the dodecyl hydrocarbon moieties in three globular cores. Each core was surrounded by a hydrophilic shell, formed by the hydrophilic and amphiphilic stretches of the polypeptide chain, and by the sulfate head groups of the detergent. The average thickness of these shells was 0.7-0.8 nm. The three-micelle complex was cleaved with trypsin at a single site, possibly in a micelle-connecting segment, into a single-micelle fragment at the carboxyl-terminal which comprised 73 SDS molecules and 163 amino-acid residues, and a dual-micelle fragment. One of the micelles within this larger fragment contained 42 SDS molecules and about 90 amino-acid residues; the other micelle contained 101 SDS molecules and about 190 amino-acid residues. The individual micelle sizes seemed to be determined by the amino-acid sequence. PMID- 2194801 TI - pH-induced insertion of the amphiphilic alpha-helical anchor of Escherichia coli penicillin-binding protein 5. AB - By treating vesicles prepared from Escherichia coli K12 with various reagents, we have investigated the mechanism by which penicillin-binding protein 5 anchors to the inner membrane. The results indicate that there are two forms of anchoring; one which is inaccessible to urea and probably inserted into the bilayer and one which is accessible. Association of the accessible form with the membrane seems to involve significant hydrophobic interaction and this form is triggered to undergo reversible 'insertion' by a decrease in pH. PMID- 2194802 TI - The roles of ATP4- and Mg2+ in control steps of phosphoglycerate kinase. AB - 1H-NMR measurements were made of solutions of yeast phosphoglycerate kinase containing the nucleotide substrate, ATP, and Mg2+ in varying concentrations in order to investigate the affect that the metal ion has on the mode of ATP binding to the enzyme. From the change in the chemical shifts of the 'basic-patch' histidine resonances (His62, His167 and His170) and the nucleotide C8H, C2H and C1'H resonances it is apparent that there are at least two ATP-binding sites on the enzyme. Downfield shifts observed for the above histidine resonances at low nucleotide/enzyme molar ratios indicates that the primary binding site involves electrostatic interactions between the nucleotide triphosphate chain and the basic-patch region of the N-terminal domain. The secondary binding site is shown to involve predominantly hydrophobic interactions between the adenosine moiety and the protein. Evidence from previous two-dimensional NMR experiments [Fairbrother et al. (1990) Eur. J. Biochem. 190, 161-169] suggests that the secondary site is equivalent to the crystallographically observed catalytic site. The affinity of the catalytic site is increased relative to the primary electrostatic site with increasing Mg2+ concentration. The possible importance of these observations in the regulation of this enzyme in vivo are discussed. PMID- 2194803 TI - Analysis of the promotors of the single-copy genes for plastocyanin and subunit delta of the chloroplast ATP synthase from spinach. AB - The promotors of the single-copy genes for subunit delta of the chloroplast ATP synthase (atpD) and plastocyanin (PC) from spinach have been sequenced, dissected and analysed in transgenic F0 and F1 tobacco plants using the bacterial GUS gene as a reporter for promotor activity. The transcription of these genes is photo controlled. The results have been compared with those obtained for the spinach rbcS-1 gene, one of the light-regulated genes encoding the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase, and for the cauliflower mosaic virus (CaMV) 35S RNA promotor. We find that the 5' upstream regions of about 1200 nucleotides contain all the sequences required for light regulation, organ-, tissue- and development-specific expression, and that they are structurally diverse. Their cis-acting elements are functionally defined. The proximal regions of the spinach promotors contain potential TATA, CAAT and T-cyt boxes at appropriate positions, but only sequence elements with low similarity to published light-responsive elements. Positive light-stimulated regions, regions with constitutive, light-independent enhancing effects and with 'silencer'-like activity in complete darkness are found in proximal and far upstream promotor segments. Highest activity of these promotors is correlated with the presence of chloroplasts but is not confined to photosynthetic tissue. Surprisingly, expression is observed in the phloem regions of transgenic leaves, leaf and floral stems, in the vascular area of anthers and in pollen. No histochemical staining has been detected in roots. The distal region of atpD located between 1137 and -590 contains elements for expression in the outer phloem, the region from -590 to -185 for activity in the inner phloem of floral stems. Similar tissue-specific patterns are observed with a fusion between the caufliflower mosaic virus 35S RNA promotor and the GUS gene. PMID- 2194804 TI - Effects of nutrients and hormones on transcriptional and post-transcriptional regulation of fatty acid synthase in rat liver. AB - The effects of nutrients and hormones on transcriptional and post-transcriptional regulation of fatty acid synthase in rat liver were investigated following cDNA cloning. When fasted rats were fed a carbohydrate/protein diet, the transcriptional rate was greatly increased even in 1 h. The transcriptional rate, mRNA concentration and enzyme induction reached maximum levels in 4 h, 8-16 h and 48 h, respectively. Although dietary carbohydrate increased each level more than protein did, both carbohydrate and protein were required to reach a high level. Corn oil feeding markedly decreased the transcriptional rate. In diabetic rats, the transcriptional rate, mRNA concentration and enzyme induction were very low in comparison with the normal. By treating the diabetic rats with insulin, however, the transcriptional rate was increased 5-fold in 1 h and 15-fold in 6 h, preceding a great increase in the mRNA and enzyme levels. On the other hand, fructose feeding or triiodothyronine treatment of diabetic rats abundantly increased the mRNA concentration and somewhat increased the transcriptional rate. Thus, it is suggested that insulin mainly stimulates the transcription of the fatty acid synthase gene, whereas triiodothyronine and fructose mainly increase the mRNA stability. PMID- 2194805 TI - Preliminary crystallographic data for protease omega. AB - Protease omega from Carica papaya L. has been purified and crystallized. The crystals are trigonal, space group P3(1)12 (or P3(2)12), with a = 7.42 +/- 0.02 nm, c = 7.79 +/- 0.02 nm with one molecule in the asymmetric unit. The crystals diffract to 0.19-nm resolution using synchrotron radiation. PMID- 2194806 TI - Components of the angiotensin system cause release of a neutrophil chemoattractant from cultured bovine and human endothelial cells. AB - Evidence suggests that angiotensin II can affect macrophage-mediated inflammatory responses; however, whether it can affect neutrophil-mediated inflammatory responses is not yet clear. We have previously demonstrated that components of the angiotensin system simulate bovine aortic and human umbilical vein endothelial cells to release a neutrophil chemoattractant. In the current study, we examined the effect of components of the angiotensin system on bovine and human pulmonary arterial and human aortic endothelial cells, and partially characterized this neutrophil chemoattractant. All endothelial cell types incubated with angiotensin II released neutrophil chemoattractant activity. This activity appeared within 1 min of exposure to angiotensin II, and was blocked by saralasin, an angiotensin II antagonist. The neutrophil chemoattractant also appeared after exposure to angiotensin I, but this effect required conversion to angiotensin II. Incubation with bradykinin, another substrate for angiotensin converting enzyme, did not cause release of the neutrophil chemoattractant. Chemoattractant release was not inhibited by indomethacin but was blocked by diethylcarbamazine or 5,8,11,14-eicosatetraynoic acid. Following extraction, the neutrophil chemoattractant partitioned completely into the organic phase. High pressure liquid chromatography demonstrated several peaks of chemoactivity, none of which co-eluted with known eicosanoid or phospholipid neutrophil chemoattractants. This study demonstrates that angiotensin II may influence neutrophil accumulation via production of neutrophil chemoattractant activity by vascular endothelial cells. PMID- 2194808 TI - Thromboxane A2 and platelets as mediators of coronary arterial vasoconstriction in myocardial ischaemia. PMID- 2194807 TI - Myocardial and coronary effects of captopril during pacing-induced ischaemia in patients with coronary artery disease. AB - It has been speculated that ACE inhibitors may have beneficial effects in patients with coronary artery disease not only by their vasodilator properties but also by an effect on an assumed local renin-angiotensin system in atherosclerotic coronary arteries. Thus, the aim of the present study was to evaluate the effect of a single intravenous infusion of captopril on haemodynamics and coronary diameter at rest and during myocardial ischaemia induced by rapid atrial pacing. The study was performed in 12 patients with coronary artery disease and exertional angina pectoris despite medical therapy. Central haemodynamics (PAO, PAP) and left ventricular end-diastolic pressure were measured. Biplane cineventriculography and coronary arteriography were performed during control pacing (10% above the normal heart rate) before and after 15 min of captopril infusion, as well as during angina pectoris induced by rapid atrial pacing before and after captopril (six patients 0.15 mg kg-1, six patients 0.3 mg kg-1). Mean aortic pressure was not significantly decreased by either 0.15 mg kg 1 or 0.3 mg kg-1, whereas mean pulmonary pressure was significantly reduced by captopril by 28% at rest and 34% during rapid atrial pacing. Neither the endsystolic volume index nor left ventricular ejection fraction was significantly affected by captopril. Left ventricular end-diastolic volume index was reduced by 9% at rest and 7% during pacing-induced angina. Left ventricular end-diastolic pressure decreased from 11 +/- 9 mmHg to 4.8 +/- 4.1 mmHg at rest after captopril, and from 10 +/- 11 mmHg to 5.1 +/- 5.0 mmHg during pacing-induced angina after captopril.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2194809 TI - Endothelium-dependent modulation of vascular tone and platelet function. AB - Endothelial cells exert potent effects on vascular tone and platelet activity by the release of autacoids. One of the functionally most important autacoids is the endothelium-derived relaxant factor (EDRF). It inhibits platelet and vascular smooth muscle activation by cGMP-dependent attenuation of the agonist-induced rise of intracellular free Ca2+. Recent experiments suggest that EDRF has a physiologic role in the control of the vascular tone of large arteries and resistance vessels. Furthermore, there is evidence that an impairment of EDRF release may be a significant pathophysiologic factor in myocardial ischaemia. Coronary vascular tone might be also affected by the endothelium-derived vasoconstrictor peptide, endothelin, but its significance for the control of coronary blood flow remains to be elucidated. PMID- 2194810 TI - Emerging role of the tissue renin-angiotensin systems in congestive heart failure. PMID- 2194811 TI - Peptidergic control of cardiovascular function: the angiotensin paradigm. AB - If we consider the chemical messengers in the central nervous system, there are about ten classic transmitters--the catecholamines, biogenic amines and amino acids--as opposed to over 50 different neuropeptides. These include previously well-established circulating hormones such as angiotensin, atrial natriuretic peptide, vasopressin and oxytocin, calcitonin and calcitonin gene related peptide (CGRP), the opioid family of peptides, gastrointestinal peptides, pituitary peptides and their releasing factors, and miscellaneous peptides such as the kinins, bombesin, gallanin, and others; all occur as neuropeptides in the brain. There is evidence supporting a role in central cardiovascular control for angiotensin, opioid peptides, substance P, neuropeptide Y, vasopressin, atrial natriuretic peptide, kinins, corticotropin releasing factor, bombesin, somatostatin, and some other peptides. They have been localized in brain areas known to be important for blood pressure regulation, and specific high-affinity peptide receptors have also been discovered. Upon central administration, these peptides produce cardiovascular effects, partly by interacting with other blood pressure-controlling neuroregulators, e.g. catecholamines and GABA. Central inhibition of brain peptide synthesis or interaction with competitive antagonists at the receptor site results in marked cardiovascular effects. Altered peptide levels and activity of synthesizing enzymes, as well as supersensitivity to the pressor action of some brain peptides, have been described in experimental models of hypertension. We are using angiotensin as a model peptide to study the peptidergic control of cardiovascular function. PMID- 2194812 TI - Basic pharmacology of ACE-inhibitors with respect to ischaemic heart disease: prostaglandins and bradykinin. AB - Experimental evidence suggests that ACE-inhibitors possess cardioprotective properties. Since ACE-inhibitors can prevent bradykinin breakdown and can stimulate prostaglandin production, it is thought that these cardioprotective effects are mediated by bradykinin and prostaglandins. This article summarizes the results indicating that bradykinin and prostaglandins, although not the only factors, do play an important role in cardioprotection by ACE-inhibitors. Special attention is paid to the presence of the sulphydryl moiety of certain ACE inhibitors. Probably, these sulphydryl group-containing ACE-inhibitors have an additional protective effect through an interaction with bradykinin or through scavenging of free radicals. However, these cardioprotective effects have not yet been shown in patients with ischaemic heart disease, although some studies indicate that ACE-inhibitors are also able to cause anti-ischaemic effects in patients. Further studies are required to establish the clinical importance of cardioprotection by ACE-inhibitors in ischaemic heart disease. PMID- 2194813 TI - Cardioprotective effects of captopril in myocardial ischaemia, ischaemia/reperfusion and infarction. AB - Several experimental studies have suggested that the sulphydryl-containing angiotensin-converting enzyme inhibitor, captopril, has cardioprotective effects in the setting of acute myocardial ischaemia, ischaemia/reperfusion and infarction. We have observed that captopril can reduce the degree of dilatation and early functional myocardial infarct expansion produced by 3 h of permanent coronary artery occlusion in anaesthetized, open-chest dogs. In addition, captopril has been shown to limit experimental infarct size, reduce the incidence of reperfusion arrhythmias, and improve contractile function of stunned myocardium. When administered chronically after myocardial infarction, both experimental and clinical evidence suggests that captopril reduces left ventricular dilatation. Captopril is currently being tested in large clinical trials as adjuvant therapy to thrombolysis. PMID- 2194815 TI - History of Teflon. AB - The main physical features of Teflon, a plastic fluorated material, are discussed. Since the 2nd World War, its uses have become numerous. PMID- 2194816 TI - Medical history of Teflon. AB - The different stages in the medical use of Teflon are recalled. After animal experimentation which started in 1949, Teflon has been used in humans since 1962 in otorhinolaryngology, since 1973 in urology and, more recently, since 1984 in the treatment of vesicorenal reflux. The long-term future is still uncertain, especially with regard to children, for whom life expectancy is long. PMID- 2194814 TI - Nuclear medicine to image applied pathophysiology: evaluation of reserves by emission computerized tomography. PMID- 2194817 TI - Ureteral lesions due to endoscopic treatment of vesicoureteral reflux by injection of Teflon: pathological study. AB - This study, based on the analysis of four samples of terminal ureter obtained at surgical resection, intends to relate the macroscopic and histologic aspect of lesions induced by Teflon injection in the ureteral wall. 6 months after the first injection and 3 months after the second one, the free ureteral lumen is compressed by an intraparietal nodule containing a central area of Teflon spherules and a rim of macrophages and resorptive multi-nucleated giant cells surrounded by a line of connective tissue without a mutilating sclerohyaline reaction. This study, however, is unable to prejudge the long-term future of Teflon or the aspect of the ureteral wall when treatment is efficient. PMID- 2194818 TI - Multicenter survey of endoscopic treatment of vesicoureteral reflux in children. AB - 17 centers answered an inquiry on the endoscopic treatment of vesicoureteral reflux. 844 children were reviewed representing 1,290 ureters treated by endoscopic injection of Teflon. The first results in cases of primary or secondary reflux showed a success rate of 82.3%. All authors report low morbidity and excellent tolerance of this technique. In view of the long-term prognosis, these results should be reanalyzed, the median follow-up presently being 1 year. The next logical step should be the development of implant material with a higher biocompatibility but the identical physical properties as Teflon. PMID- 2194819 TI - A new antireflux operation. AB - A new technique for the correction of reflux is presented. The technique is simple, rapidly accomplished without mobilization of the ureter and virtually free of complications. The procedure has been done successfully on 85 (92%) of 92 ureters in the first 55 patients. The most important contribution of this procedure is the decrease in manipulation of the ureter, resulting in minimal disturbance of the blood supply and in a straight course of the ureter without the risk of kinking or obstruction. PMID- 2194820 TI - Homologous desensitization of the effects of endothelin on rabbit aorta rings and on cultured rat aorta smooth muscle cells. AB - The effects of endothelin-1 on normal and everted rabbit aorta rings and on cultured rat aortic smooth muscle cells were studied. Endothelin-1 (40 nM) contracted both normal and everted rings, and was still able to induce a prolonged contraction in Ca2(+)-free medium. Treatment of cultured cells with 100 nM endothelin-1 caused a sharp transient increase in 45Ca2+ efflux. The contractile and 45Ca2+ responses showed severe and specific desensitization towards endothelin-1; the responses to angiotensin II and adrenaline were not affected. The contractile responses to endothelin-1 were not affected by previous treatment with angiotensin II or with the angiotensin receptor antagonist, [Sar1,Ala8]angiotensin II. It is concluded that endothelin-1 acts on its own specific receptors to elicit Ca2+ mobilization from both intracellular and extracellular sources. PMID- 2194821 TI - Acute effects of antihypertensive agents on cerebral blood flow in hypertensive rats. AB - The acute effects of various antihypertensive agents on cerebral blood flow and mean arterial pressure (MAP) were studied in anesthetized (amobarbital 100 mg/kg) spontaneously hypertensive rats. Cerebral blood flow in the cortex and thalamus was measured by the hydrogen clearance method before and during a 60-min i.v. infusion of calcium antagonist (nifedipine), angiotensin converting enzyme inhibitor (captopril) or beta-blocker (propranolol). Nifedipine, 30 or 150 micrograms/kg per h, decreased dose dependently the MAP by 20 or 31%, and concomitantly increased cortical blood flow by 28 or 74%, and thalamic blood flow by 51 or 64%, respectively. Captopril, 10 or 100 mg/kg per h, decreased MAP by 7 or 14%, but changed cerebral blood flow minimally. In contrast, propranolol, 1.0 or 5.0 mg/kg per h, decreased MAP by 13 or 11%, with a concomitant reduction of cortical and thalamic blood flow by 20 or 15 and 33 or 37%, respectively. It is concluded that the changes in cerebral blood flow in response to hypotension are varied by antihypertensive drugs depending on the direct or indirect effect of the drugs (dilatation or constriction) on cerebral vessels. Nifedipine seems to dilate while propranolol constricts cerebral vessels. PMID- 2194822 TI - Paraxanthine displaces the binding of [3H]SCH 23390 from rat striatal membranes. AB - We present evidence showing that paraxanthine (1,7-dimethylxanthine), the main metabolite of caffeine in man, displaces the binding of [3H]SCH 23390, a radioligand which selectively labels dopamine D-1 receptors when used at low concentrations, from striatal membranes of the rat. The displacement was competitive and indicated the existence of two affinity states (Hill coefficient = 0.49; K(high) = 0.15 microM; K(low) = 95.9 microM, %R(high) = 32.4). When the stable GTP analog Gpp(NH)p was included, the displacement curve indicated the presence of only the low-affinity state (Hill coefficient = 1.16; Ki = 72.1 microM). However, paraxanthine did not displace the specific binding of [3H]spiperone. After injection of 30 mg/kg s.c. of caffeine, a maximum of 10 microM of paraxanthine was found in striatal homogenates, which could be sufficient to occupy dopamine D-1 receptors. Our results suggest that a dopaminergic action of paraxanthine could be involved in the behavioural stimulation produced by caffeine. PMID- 2194823 TI - Inhibition of feeding by ACTH-(1-24): behavioral and pharmacological aspects. AB - The time course of the behavior of rats fasted for 24 h was analyzed with observation starting either 10 or 60 min after the i.c.v. administration of ACTH (1-24) (4 micrograms/animal). The anorectic effect of this peptide was direct and specific because it could be dissociated in time from the grooming-inducing effect. The effect is a central one, not linked either to an interaction with the peripheral feeding-regulatory system, or to the release of adrenal steroids. ACTH (1-24), like corticotropin-releasing factor (CRF), is capable of antagonizing the stimulation of feeding seen during starvation, insulin (10 IU/kg s.c.)-induced hypoglycemia, stimulation of GABAergic (muscimol, 250 ng/rat i.c.v.), noradrenergic (norepinephrine, 20 micrograms/rat i.c.v.) or opioidergic systems. The data suggest that both CRF and ACTH may be considered as putative mediators in the production of stress-induced anorexia. PMID- 2194824 TI - Selective adenylate cyclase increase in the limbic area of long-term imipramine treated rats. AB - Long-term administration of imipramine to rats produced an increase in the Vmax of forskolin- or guanylylimidodiphosphate (Gpp(NH))p-activated adenylate cyclase only in the limbic area. This effect was prevented by the daily administration of alpha-methyl-p-tyrosine (alpha-MPT), given together with imipramine, at a dose (50 mg/kg) which had no effect on adenylate cyclase activity per se. The time course of the effects of chronic imipramine on dopaminergic transmission in the limbic area showed that the decrease in both D-1 receptor number and adenylate cyclase stimulation by dopamine (DA) reached significance on day 8 of treatment and were maximal on day 15. The Vmax of the enzyme started to increase on day 15 and was further increased on day 21. Possible mechanisms underlying these effects are discussed. PMID- 2194825 TI - Stimulatory effect of cyclosporine A on endothelin secretion by a cultured renal epithelial cell line, LLC-PK1 cells. PMID- 2194826 TI - A sensitive sandwich enzyme immunoassay for measurement of insulin on microtiter plates. AB - A sensitive enzyme immunoassay for the measurement of insulin in human sera on microtiter plates was established. The assay is based on the sandwich technique with guinea pig anti-insulin IgG adsorbed at microtiter plate wells, human insulin as standard and the same anti-insulin IgG labeled with horseradish peroxidase. Standards used cover a range from 0 to 1200 pmol/l with a detection limit of 10 pmol/l. Coefficients of variation between 3-7% for intraassay precision and 5-11% for interassay precision were obtained over the concentration range of 80-1000 pmol/l. The correlation of EIA-data with those of a commercially available double antibody radioimmunoassay (r = 0.98) could be expressed by the equation: EIA = 0.97 RIA - 57 pmol/l. Normal fasting serum insulin concentrations in healthy subjects ranged from 11-165 pmol/l. In subjects with potentially diminished basal values concentrations of 10-79 pmol/l were determined. The insulin response in oral glucose tolerance tests of children was discussed, who had a constitutional tall stature or Turner's syndrome, respectively. PMID- 2194827 TI - Two-dimensional crystallization of reaction centers from Chloroflexus aurantiacus. AB - Two-dimensional crystals of photosynthetic reaction centers from Chloroflexus aurantiacus were obtained from protein-lipid-detergent micelles by detergent dialysis. The size of crystals was up to 2 microns. Some of them were multilayered crystals. However, other crystal forms were also observed. Preliminary image processing analysis showed that crystals of one crystal form referred to two-sided plane group p2 and had the following unit cell parameters: a = 17.6 nm, b = 18.0 nm, gamma = 84 degrees. The contour map of the crystal stain-excluding region was calculated by the Fourier-filtering procedure at about 2 nm resolution. PMID- 2194828 TI - Evidence for the ability of L10 ribosomal proteins of Salmonella typhimurium and Klebsiella pneumoniae to regulate rplJL gene expression in Escherichia coli. AB - Genes rplJ, coding for ribosomal protein L10 of Salmonella typhimurium and Klebsiella pneumoniae, have been cloned on pUC plasmid. The resultant multicopy recombinant plasmids were detrimental for the growth of normal JM101 E. coli host cells and harmless for the mutant JF3029 host. This negative effect is the evidence for the ability of heterologous L10 proteins to regulate expression of rplJL genes in E. coli. Nucleotide sequence was determined completely for S. typhimurium rplJL' DNA portion and partially for rplJL' genes of K. pneumoniae. According to the nucleotide sequence data obtained three amino acid substitutions differ L10 proteins of S. typhimurium and E. coli and the long range, providing for the coupled translations of L10 and L7/L12 cistrons in E. coli mRNA is also valid for S. typhimurium and K. pneumoniae. PMID- 2194829 TI - Substrate specificity of two kallikrein family gene products isolated from the rat submaxillary gland. AB - Two proteinases which belong to the tissue kallikrein family were purified from rat submaxillary glands. These proteinases correspond to the products of the RSKG 7 and the rGK8 genes, as shown by the comparison of their partial amino-acid sequence with that deduced from nucleotide sequences. These two proteinases, kallikrein k7 and kallikrein k8, exhibit a marked preference for cleavage after arginyl residues. However, their overall specificities towards synthetic fluorogenic substrates differ significantly from each other and from that of true tissue kallikrein. Kallikrein k7 is strongly inhibited by soybean trypsin inhibitor, whereas kallikrein k8 is not. These data, demonstrating the individual specificity of these kallikrein-like proteinases, suggest that they could be involved in the processing of peptides other than kinins. PMID- 2194830 TI - Crystallization and preliminary X-ray crystallographic study of interleukin-8. AB - Interleukin-8 (neutrophil-activating factor; NAP-1) has been crystallized by the vapour diffusion technique to give single crystals suitable for three-dimensional structural study at a resolution higher than 2.4 A. The crystals belong to the space group P3(1)21 or P3(2)21 and have unit cell dimensions a = b = 40.9 A, c = 90.3 A. PMID- 2194831 TI - Expression of genes coding for pS2, c-erbB2, estrogen receptor and the H23 breast tumor-associated antigen. A comparative analysis in breast cancer. AB - Expression of the gene coding for a new breast tumor-associated antigen, H23, was compared to expression of genes coding for pS2, c-erbB2 and estrogen receptor (ER). Comparison involved mRNA expression in normal and malignant breast tissues as well as in non-breast tumors. Results obtained by RNA dot blot and Northern hybridizations showed that expression of the H23 antigen coding gene is a discriminatory marker in human breast cancer. It is expressed in 92% of breast tumors whereas 69%, 62% and 56% of breast tumors demonstrate significant mRNA levels of c-erbB2, ER and pS2, respectively. Non-malignant or normal breast tissue expresses much lower levels of the H23 antigen mRNA. From the comparative analysis presented here it is concluded that the gene coding for H23 antigen furnishes a most useful marker for human breast cancer. PMID- 2194832 TI - Functional expression of the mutants of the chloroplast tRNA(Lys) gene from the liverwort, Marchantia polymorpha, in Escherichia coli. AB - The anticodon of the tRNA(Lys) gene (trnK) in the liverwort, Marchantia polymorpha, was artificially converted to an amber anticodon. This mutant tRNA(Lys) (CTA) gene carrying either the intron of the C27-C43 mismatch at the anticodon-stem is not functional in Escherichia coli, but without both of them, it does work as a tRNA(Lys) amber suppressor. PMID- 2194833 TI - Human c-myc gene contains a regulatory site similar to consensus of interferon response sequence (IRS). AB - Expression of c-myc proto oncogene is regulated by multiple mechanisms. Here, we report that the consensus of the regulatory region of interferon-dependent genes, GGAAAN1-3 GAAA, was found after computer search in the 5'-terminal flank of human c-myc gene in position (-76:-67). In vitro transcription of c-myc gene fragments showed that the consensus region competes with oligonucleotide GGGAAAATGAAACT for binding to specific protein(s). This oligonucleotide was shown to bind selectively the interferon-dependent positive transcription factor. Transcription of c-myc fragments lacking 5'-terminal region up to positions -101 or +71 was initiated at two sites located in the first intron. These sites did not coincide with P1 in vivo RNA cap-site. Binding of the protein factor(s) to the regulatory region of c-myc gene -76:-67 blocked the in vitro transcription initiated in the first intron. PMID- 2194834 TI - Comparison of the D1/D2/cytochrome b559 reaction centre complex of photosystem two isolated by two different methods. AB - Photosystem 2 reaction centre complexes prepared either by solubilisation with Triton X-100 and subsequent exchange into dodecyl maltoside or by a procedure involving a combination of dodecyl maltoside and LiClO4, were characterised in terms of chlorophyll a, pheophytin a, beta-carotene and cytochrome b559 content. Time-resolved chlorophyll fluorescence decay kinetics were measured using both types of complexes. Our data show that the isolated photosystem two reaction centre complex contain, for two pheophytin a molecules, close to six chlorophyll a, two beta-carotene and one cytochrome b559. No major differences were observed in the composition or the kinetic characteristics measured in the samples prepared by the different procedures. Time-resolved fluorescence measurements indicate that more than 94% of the chlorophyll a in both preparations is coupled to the reaction centre complex. PMID- 2194835 TI - In vivo processing of N-terminal methionine in E. coli. AB - The processing of amino-terminal methionine from cytosolic proteins in E. coli has been investigated in vivo, using amino-terminal-extended human growth hormone (hGH) as a model system. Twenty different hGH-genes with the sequence Met-Xxx-Glu Glu-hGH where Xxx denotes each of the 20 different amino acids, were constructed and expressed in E. coli. Following purification of the products, the N-terminal amino acid sequences (10 cycles) were determined. The results demonstrate that the removal of methionine is dependent on the amino acid adjacent to methionine, and that the processing is strongly correlated to the radius of gyration of this amino acid. In addition, measurement of the hGH expression level from the 20 clones demonstrated that the small difference in the amino acid extension leads to a change in the specific hGH expression rate. PMID- 2194836 TI - Metal ion co-ordination in the DNA binding domain of the yeast transcriptional activator GAL4. AB - The structure of the DNA binding domain of the yeast transcriptional activator GAL4 was investigated by extended X-ray fine structure (e.x.a.f.s.). Two samples of GAL4 were studied, one containing cadmium as a structural probe (Cd(II)GAL4) and the other containing the 'native' zinc (Zn(II)-GAL4). The results suggest that the structure of the DNA binding domain of GAL4 contains a two metal ion cluster distinguishing it from the 'zinc finger' proteins typified by the Xenopus laevis transcription factor TFIIIA. PMID- 2194837 TI - An X-ray solution scattering study of the cofactor and activator induced structural changes in yeast pyruvate decarboxylase (PDC). AB - Structure and activation pattern of pyruvate decarboxylase (PDC) from yeast was studied by synchrotron radiation X-ray solution scattering. The results give a direct proof that the reversible deactivation of PDC at pH 8.0 is accompanied by the dissociation of the tetrameric holoenzyme into dimeric halves. The kinetics of this process was followed. At pH 6.5 the dimeric halves reassociate to a tetramer even in the absence of cofactors. The changes of the scattering pattern upon binding of the substrate-like activator pyruvamide indicate that the structure expands in the course of the enzyme activation. PMID- 2194838 TI - Purification and some characteristics of chicken liver L-2-hydroxyacid oxidase A. AB - The isozyme A of L-2-hydroxyacid oxidase is a peroxisomal flavoenzyme that catalyzes the oxidation of short-chain aliphatic L-2-hydroxyacids in many tissues of higher organisms. A new purification procedure allowed us to obtain a 1400 fold purified enzyme from chicken liver. The N-terminal amino acid of the polypeptide chain was found to be blocked as that of spinach glycolate oxidase, contrastingly with that of rat kidney isozyme B. Its amino acid composition was comparable to that of other known L-2-hydroxyacid oxidases. Despite different substrate specificity, some immunological identity was observed between chicken liver L-2-hydroxyacid isozyme A and rat kidney isozyme B. PMID- 2194839 TI - Expression and pharmacological characterization of the human M1 muscarinic receptor in Saccharomyces cerevisiae. AB - The yeast S. cerevisiae has been examined as a heterologous host for the expression of mammalian neurotransmitter receptors which couple to guanine nucleotide regulatory (G) proteins. A cloned gene encoding the M1 subtype of human muscarinic receptor (HM1) was transformed into S. cerevisiae on a high copy plasmid under the control of the promoter for the yeast alcohol dehydrogenase (ADH) gene. Northern blotting demonstrated the presence of HM1 transcripts in transformants, and crude membranes prepared from these cells showed saturable binding of the muscarinic antagonist [3H]N-methyl scopolamine with a Kd of 179 pM and Bmax of 20 fmol/mg protein. Competition binding studies revealed pharmacological properties for these sites which were comparable to those reported for the M1 site in mammalian tissues. Yeast expressing HM1 did not exhibit high affinity agonist binding or cell-cycle arrest in the presence of muscarinic agonists, indicating that the mammalian receptor did not couple to the endogenous yeast G protein. PMID- 2194840 TI - Prokaryotic 20 beta-hydroxysteroid dehydrogenase is an enzyme of the 'short chain, non-metalloenzyme' alcohol dehydrogenase type. AB - The primary structure of 20 beta-hydroxysteroid dehydrogenase from Streptomyces hydrogenans was determined after FPLC purification of a commercial preparation. Peptides obtained from different proteolytic cleavages were purified by reverse phase HPLC. The 255-residue structure deduced was found to be distantly homologous to those of Drosophila alcohol dehydrogenase and several other dehydrogenases, establishing that prokaryotic 20 beta-hydroxysteroid dehydrogenase as a member of the 'short-chain alcohol dehydrogenase family'. With the enzymes characterized, the identity is greatest (31-34%) towards 4 other prokaryotic dehydrogenases, but the family also includes mammalian steroid and prostaglandin dehydrogenases. These enzymes are low in Cys and have a strictly conserved Tyr residue that appears to be important. PMID- 2194841 TI - Purification, some properties and nucleotide sequence of 5-carboxymethyl-2 hydroxymuconate isomerase of Escherichia coli C. AB - As part of an investigation into the evolution of catabolic pathway enzymes a cloned gene encoding the Escherichia coli C 5-carboxymethyl-2-hydroxymuconate (CHM) isomerase, an enzyme of the homoprotocatechuate catabolic pathway, was used to produce large amounts of the protein. The isomerase was purified to homogeneity and some of its properties determined. The reaction occurred optimally at pH 7.6 and the specificity constant was 5.8 x 10(5) M-1.s-1 with CHM and 6.0 x 10(2) M-1.s-1 with 2-hydroxyhepta-2,4-diene-1,7-dioate, the substrate of a second isomerase in the pathway. The pure protein showed one type of subunit of Mr 14,000 whilst the molecular mass of the native enzyme was 30,000, suggesting that it was a dimer of identical subunits. The first 19 N-terminal amino acids were sequenced and the data used to confirm that the open reading frame of 378 bp, identified from the nucleotide sequence, encoded the CHM isomerase. PMID- 2194842 TI - Expression of catalytically active radish 3-hydroxy-3-methylglutaryl coenzyme A reductase in Escherichia coli. AB - Two fragments of a cDNA encoding radish 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) were cloned into the vector pET-8c and expressed in Escherichia coli. The large fragment, encoding both the membrane and the cytosolic domains, was expressed at low level, essentially as an insoluble protein without enzymatic activity. In contrast, the fragment encoding only the cytosolic domain was expressed at a high level in a catalytically active form. The amount of soluble active enzyme in cell-free extracts of E. coli dramatically increased when the temperature during the induction was lowered from 37 degrees C to 22 degrees C. PMID- 2194844 TI - Cholesterol, lipoproteins, lipid profiles: a challenge in patient education. PMID- 2194843 TI - Unwinding of duplex DNA during transcription initiation at the Escherichia coli galactose operon overlapping promoters. AB - We have used potassium permanganate as a probe to detect DNA duplex unwinding in vitro, in open complexes between E. coli RNA polymerase and DNa fragments carrying the E. coli galactose operon regulatory region. This zone contains 3 overlapping promoters which specify transcription initiation at 3 distinct startpoints. We have used mutant gal derivatives carrying different single point mutations, each of which allows initiation from only one of the 3 start sites. This has allowed us to compare duplex unwinding in open complexes at the 3 different promoters, and to show that the extent of the unwinding is similar in each case. Further, the pattern of DNA modification by potassium permanganate suggests a model for discrimination between the upper and lower strands. Finally, we show that DNA modification by potassium permanganate at the gal promoters is the same in vivo as in vitro. PMID- 2194845 TI - Advances in ventilator therapy: high-frequency, pressure support, and nocturnal nasal positive pressure ventilation. PMID- 2194846 TI - Measurements of hemodynamics in side-lying positions: a review of the literature. PMID- 2194847 TI - [Bubble formation at the metal-ceramic bond]. PMID- 2194848 TI - [Plastic basics of Silicoater-MD procedures]. PMID- 2194849 TI - [Persistent spontaneous erythema caused by topical use of fumaric acid monoethyl ester--an obligate mast cell degranulation?]. AB - In 12 healthy volunteers the topical application of monoethyl fumarate caused a spontaneous persistent erythema. Systemic application induced flush. In urticaria pigmentosa the influence was significant higher than in normal skin. This fact suggests a mast cell degranulation caused by monoethyl fumarate. PMID- 2194850 TI - [Acrosyringial keratinocytes--no abnormal differentiation in psoriasis vulgaris]. AB - Histochemical investigations were performed in normal and psoriatic epidermis to evaluate possible differences in the acrosyringial reactivity. Luminal (abundant in glycoconjugates, immunoreactive) and outer (almost nonreactive) epithelial cells could be distinguished. Psoriasis did not affect the staining pattern. The findings argue against a primary involvement of acrosyringial keratinocytes in the abnormal differentiation pathway of psoriatic epidermal cells. Moreover, they underline the relative independence of the acrosyringium from interfollicular epidermis. PMID- 2194851 TI - [Leiomyosarcoma of the skin--a diagnostic and therapeutic problem tumor]. AB - It is reported about an uncommon problematic tumour of the skin by means of 3 patients with a leiomyosarcoma. The own experiences in this field are compared with the not very extensive literature, and the clinical and histological criteria of diagnostic are discussed also therapeutical recommendation in consideration of the prognostic aspects are derived. PMID- 2194853 TI - [Contraception in the diabetic woman]. AB - The metabolic and vascular effect of oestroprogestative treatments make the choice of a contraception difficult for the diabetic women. More than the action on blood glucose it is the effect of Ethynyl-oestradiol on blood pressure, blood lipids and hemostasis which makes problem in case of diabetes. Local contraceptive methods are generally preferred owing to the absence of systemic effect and their good tolerance in a diabetic women. The choice of a method must take into consideration not only the type of diabetes but also the existence or absence of micro and macro-angiopathy. PMID- 2194852 TI - [Effect of pepstatin A on Candida albicans infection in the mouse]. AB - The intravenous injection of 10(6) to 10(7) Candida albicans cells revealed to be a reliable model in mice produce infections of the kidney. Higher germ contents could be yielded in the kidney after the application of protease positive Candida strains as compared to protease negative ones. Additionally, after the infection with protease positive strains a proteolytic activity could be found in the kidney homogenates in vitro on casein plates. The modulation of this Candida infection by pepstatin A, an inhibitor of extracellular yeast proteases in vitro, has also been studied in the same mice model in vivo. The growth rate of Candida albicans has been measured in the left kidney by counting the germ content as described by Haenel. Infections could be reduced after single doses of 120 micrograms pepstatin A contrary to 60 micrograms pepstatin A. The same was with three doses of 180 micrograms at 24 h intervals. This protease inhibitory effect could also be found in kidney homogenates in vitro on casein plates and lasted until 48 h post injection. On the basis of this positive effects on the Candida infection in mice pepstatin A should be considered as an adjuvans in the therapy of severe yeast infections. PMID- 2194854 TI - [Antidiabetic treatment and monitoring during pregnancy in diabetes]. AB - In pregnant diabetic women one of the goals of antidiabetic treatment and monitoring is to maintain blood glucose near normal values between 4.4 and 6.1 mmol/l. If possible such values should be obtained before conception. To reach these goals four components of health care delivery are of major importance. Education dealing with contraception and planification of the pregnancy, diet modified according to the state of pregnancy, self blood glucose monitoring to allow anticipatory optimized insulin therapy. During pregnancy the systematic use of continuous subcutaneous insulin infusion does not seem to be associated with any significant benefit dealing with metabolic control or the perinatal and neonatal morbidity and mortality. In pregnant diabetic patients the usefulness of the dosage of glycated haemoglobin is limited due to the spontaneous fluctuations of this value during pregnancy, as well as the delay of the variation of this index during a period of poor glycemic control. In this condition glycated proteins as fructosamine may be more useful but many technical problems for this determination are still to be solved. PMID- 2194855 TI - [Obstetric management and delivery in diabetics]. AB - A review of the obstetrical management of diabetic pregnancies is presented. The best way to avoid complications is to achieve the best possible diabetic control. Ultrasonics are able to determine gestational age in the first weeks of pregnancy, to detect fetal malformations and to follow fetal growth. At the end of pregnancy, fetal heart rate monitoring is the golden standard to judge fetal well being. Delivery at term is of paramount importance. The presence of fetal macrosomia is an important parameter of the decision of the mode of delivery. PMID- 2194856 TI - [Diabetic retinopathy and pregnancy]. AB - The problem concerning the influence of pregnancy on diabetic retinopathy is still a matter for discussion. The questions are: can the pregnancy itself influence the onset of a retinopathy? and can a pregnancy worsen the prognosis of a retinopathy and if it is the case is there any difference regarding the type of the retinopathy: background or proliferative? Despite controversies in the literature, it seems that: If no retinopathy is present at the onset of the pregnancy, the risk for developing retinal complications is very low. A background retinopathy can worsens and may become proliferative. But improvement is often observed in post-partum. A proliferative retinopathy worsen very frequently and the proper management of patients with this type of retinopathy is of extreme importance regarding to the risk of complications and loss of vision. Before the advent of photocoagulation, the alternative to therapeutic abortion was pituitary ablation. Now, the photocoagulation became the treatment of choice for proliferative retinopathy with the same results in pregnant or non pregnant woman. But the proliferative retinopathy is associated with a high incidence of foetal morbidity. Some studies provide evidence that changes in background retinopathy may be related to the degree of diabetic control achieved during pregnancy. The rapidity of improvement in diabetic control may be critical. Diabetic women who are wishing pregnancies may undergo ocular examination with angiography. During pregnancy strict ocular examination is necessary through dilated pupils. Angiography does not seem to induce any side effect on pregnant women. PMID- 2194858 TI - [Controlling hypertension in the pregnant diabetic woman]. AB - High blood pressure occurs in many pregnant diabetic patients (30 to 40 p cent), and it is associated with significant impairement of fetal prognosis. Hypertension is no doubt a marker of the vascular diabetic disease, which obviates an adequate placentation. Proper antihypertensive management is necessary in those patients, but its prognostic importance is far less than is that of a perfect glycemic control. Antihypertensive therapy differs in some aspects from what is should be in non-pregnant patients: first, compounds such as angiotensin converting enzyme inhibitors, or calcium-channel blockers are not considered safe in pregnant women, whereas they are the first choice in non pregnant diabetics. Second, over-control of blood pressure is very harmful to fetal growth, and should be carefully avoided. Finally, present literature lacks proper controlled studies, which could help in designing the best antihypertensive therapeutic strategy in pregnant diabetic patients. PMID- 2194857 TI - [Pregnancy and diabetic nephropathy]. AB - The impact of nephropathy on the diabetic pregnancy is reviewed. Proteinuria and blood pressure increase, this increase is generally reversible after delivery and the progression of renal insufficiency remains generally unchanged. Arterial hypertension seems to be the only contraindication to pregnancy in a diabetic women with nephropathy. Percentage of premature delivery by cesarean section is high and increases the frequency of hypotrophy and post natal complication especially the respiratory distress of the new born. However, the progress in pediatric intensive care allow the same prognostic what so ever the diabetic women had renal insufficiency or not. The follow up of these pregnancies is assumed by a team of diabetologist, nephrologist and gynecologist. Short acting insulin is mandatory, hypotensive drugs must be used carefully. In spite of the low number of published cases a pregnancy may be successful in a diabetic women after renal transplantation or even after renal and pancreatic transplantation. PMID- 2194859 TI - [Maternal and fetal prognosis during pregnancy in diabetic women]. AB - Mortality and morbidity of diabetic pregnancy have decreased markedly during the last decades. Abortions occur more frequently than in control women. Perinatal mortality has declined, especially in large centers. Morbidity remains important: two thirds of the infants experience some morbidity, mainly due to prematurity and malformations. Among factors of prognosis, careful control of maternal diabetes before conception until delivery is the main point. For each period of pregnancy, a bad glycemic control in the mother is associated with a complication in the infant. Hypertension and diabetic neuropathy are risk factors of prematurity. Congenital malformations become in the large centers the main source of mortality and morbidity in infants of diabetic mothers. PMID- 2194860 TI - [Genetic counseling of diabetics]. AB - The information and counselling of diabetic patients and their families requires for the practitioner to know about some fundamental aspects of diabetes and in particular, to distinguish between the different types of diabetes with different causes, pathogenetic mechanism and modes of inheritance. Recent developments in the fields of immunogenetics have improved the understanding of type I diabetes, an auto-immune disease associated with HLA and made possible the identification of genetically susceptible individuals. The etiology of type II diabetes, by far the most frequent form, remains unknown. In the absence of genetical markers, the screening of predisposed subjects is, however, useful in order to propose preventive measures. PMID- 2194861 TI - [Gestational diabetes]. AB - Gestational diabetes defined by either glucose intolerance or overt diabetes discovered during pregnancy is a real nosologic entity which is associated with risks for both foetus and mother. Unfortunately biological definition of gestational diabetes remains controversial. In North America it is defined by O'Sullivan's criteria (OGTT with 100 g of glucose for 3 hours), in Europe it is defined by WHO's criteria (OGTT with 75 g of glucose for 2 hours). Strategy for selection of high risk women who have to be submitted to OGTT is also matter of debate. Despite these uncertainties, everybody agrees that gestational diabetes is associated with high risk of foetal macrosomia and high rate of cesarean section. For the mother, gestational diabetes is a marker of future development of diabetes. Most of gestational diabetes are related to type II diabetes but some cases of type I diabetes are preceded by gestational diabetes. The treatment of gestational diabetes depends upon the severity of glucose intolerance. It is resumed by dietetic intervention associated, if necessary, with insulin therapy. PMID- 2194863 TI - Holoacardius: antenatal diagnosis and pathogenetic evaluation: a case report. AB - A case of Holoacardius is reported by the authors. The literature is reviewed, and a pathogenetic sequence responsible for the syndrome is proposed on the basis of the pathologic data. PMID- 2194862 TI - [Pregnancy in the diabetic woman must be programmed]. PMID- 2194864 TI - Brain metastases in epithelial ovarian carcinoma; two case reports. AB - The cases of two patients with epithelial ovarian carcinoma who had been treated with surgery and cisplatin-containing combination chemotherapy and had developed brain metastases are described. Modern protocols for management of advanced-stage epithelial ovarian carcinoma have resulted in prolonging the lives of the patients sufficiently for central nervous system metastases to become apparent and possible resistence of the 'blood brain' barrier to the currently used chemotherapeutic agents may have left the CNS 'unprotected' from metastases. PMID- 2194865 TI - Ultrasound screening for fetal urinary tract malformations: a prospective study in general population. AB - Routine ultrasound examination at a first level ultrasound unit was performed on 4586 fetuses in general pregnant population at 18 and 34 weeks, to detect urinary tract malformations. Suspected renal abnormality was confirmed by postnatal investigations. Infants were followed up to 2-4 years to detect any renal malformations missed in screening. Urinary tract abnormalities were observed antenatally in 27 fetuses, eight cases at 18 weeks, and 19 cases at 34 weeks. An anteroposterior diameter of renal pelvis of 1 cm or more was the criterion for fetal hydronephrosis, which was the main ultrasound finding in 18 fetuses showing 24 hydronephrotic kidneys. In five cases, slight hydronephrosis disappeared spontaneously after birth, explaining the five 'false positive' cases of the study. Four children had renal abnormalities that were missed antenatally. The incidence of true urinary tract malformations detected by screening antenatally was 0.48%, and the overall incidence after 2-4 years follow-up was 0.57%, which is much higher than reported earlier in series without routine ultrasound screening. The antenatal screening showed a sensitivity of 84.6%, a specificity of 99.9%, a positive predictive value of 81.5%, and a negative predictive value of 99.9%. The main differential diagnostic problems occurred in two fields: in differentiating (1) functional hydronephrosis from obstructive uropathy, and (2) multicystic renal dysplasia of Potter's type IV from severe hydronephrosis. The prenatal diagnosis in cases with definitive renal abnormality corresponded to the postnatal diagnosis in 19/22 (86.4%) of the cases. 68% of the infants with urinary tract anomaly survived, 60% of them undergoing postnatal surgery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2194866 TI - Chorioamnionitis in relation to gestational outcome in a Swedish population. AB - In a histopathological study, from a homogeneous Swedish population with a better than average socio-economic standard, placentas from 161 singleton infants small for gestational age (SGA) and 322 singleton infants appropriate for gestational age (AGA) were examined for the presence of inflammation in the placental parenchymal membranes, cord and decidua. Acute chorioamnionitis including funiculitis was found in 13.4% of the total material, in 17% of term AGA-infants (GA, greater than or equal to 38 weeks), in 13% of preterm AGA-infants (less than or equal to 37 weeks) and in 6.8% of SGA-infants (p less than 0.001, compared to term AGA). Acute chorioamnionitis was correlated to vaginal delivery (p less than 0.01), rupture of the membranes greater than 24 hours (p less than 0.01), nulliparity (p less than 0.05) and amniocentesis (RR = 1.7). In nulliparous, chorioamnionitis was related to duration of labor greater than 16 hours (p less than 0.01). Streptococcal (p less than 0.01) and anaerobic vaginal infections (p less than 0.05) were also related to chorioamnionitis. Of 17 infants with sepsis, 6 had chorioamnionitis (p less than 0.05). Decidual inflammation was chronic in type and found in 4.5% of the placentas and was not related to chorioamnionitis, but to parity (p less than 0.05) and term AGA-infants (p less than 0.001). PMID- 2194867 TI - Suspected postpartum endometritis: a controlled clinical trial of single-agent antibiotic therapy with Amox-CA (Augmentin) vs. ampicillin-metronidazole +/- aminoglycoside. AB - Endometritis is the commonest postpartum complication and is one of the leading causes of maternal morbidity, if not mortality. The object of the present clinical trial was to assess the efficiency of single-agent therapy with Amox-CA (Augmentin) (formulation which includes a beta-lactamase inhibitor), against standard treatment which necessarily combines two or three antibiotics depending on the clinical severity of the case. 101 patients were evaluated in this comparative prospective randomized study. The mild forms were defined by a temperature between 37.9 and 38.4 degrees C and the severe forms by a temperature of more than 38.5 degrees C (which alone required treatment with three antibiotics). The time until the return of apyrexia and the clinical cure rate, as well as duration of treatment, were identical in both groups. Tolerance was good: no side effect requiring discontinuation of treatment occurred. In the population value, the use of a single-agent therapy with amoxycillin/clavulanic acid is not significantly different from a double or triple-agent regimen, and the convenience is increase. PMID- 2194869 TI - Changes induced by glucose in the plasma membrane properties of pancreatic islets. AB - Partially purified membranes obtained from rat pancreatic isolated islets preincubated for 3 min with 3.3 and 16.6 mM glucose were labelled with 1,6 diphenyl-1,3,5-hexatriene to study fluorescence polarization. Other islets, incubated for 5 min with the same glucose concentration, were extracted and phospholipids separated by thin-layer chromatography. The composition of phospholipids of fatty acids was then studied by gas-liquid chromatography. Arrhenius plots of the microviscosity in membranes obtained from islets exhibited two components, a steeper slope below 18 degrees C and a gentler slope above 18 degrees C, indicating greater flow activation energy at temperatures below the transition point. Exposure of islets to 16.6 mM glucose significantly increased the flow activation energy (delta E), below and above the transition point. Islets incubated for 5 min with 16.6 mM glucose showed an increase in the percentage composition of 12:0 and 18:2 together with a decrease in the 20:2 W6 and 22:3 W3 fatty acids esterified to phospholipids. Regardless of these changes, no significant alterations occurred in the proportion of saturated fatty acids or in the double bond index; these measurements therefore did not account for the effects of glucose concentration in flow activation energy. The thermotropic changes reported here might be the consequence of some degree of disorder induced by glucose upon the membrane structure. This order alteration could either favor the membrane fusion which occurs during the emiocytosis or only reflects the consequence of such a process. PMID- 2194868 TI - Adult respiratory distress syndrome as a complication of acute pyelonephritis during pregnancy. AB - Two cases of ARDS as a complication of acute pyelonephritis during pregnancy are presented. The severity of the clinical condition necessitated treating both patients by mechanical ventilation with high positive-end expiratory pressure. The review of the only six other similar cases already reported (only one needing vigorous respiratory treatment) as well as the two cases presented in this report show that the pyelonephritic aetiology of ARDS in pregnancy is very rare. Nevertheless, any septic condition could be complicated by respiratory failure in pregnancy. ARDS must be suspected in those patients suffering from urinary tract infection in which signs of hypoxia appeared during the third trimester of pregnancy. Early recognition of the syndrome, closed monitoring and vigorous treatment can prevent maternal complications and/or fetal distress. PMID- 2194870 TI - An assessment of the benefits of intrapartum fetal monitoring. PMID- 2194871 TI - Technology assessment in teaching hospitals. PMID- 2194872 TI - Effects of a tumour promoter, 12-0-tetradecanoyl-phorbol-13-acetate (TPA), on expression of differentiated phenotype in the chick retinal pigmented epithelial cells and on their interactions with the native basement membrane and with artificial substrata. AB - Chick retinal pigmented epithelial (RPE) cells grown in vitro on basement membrane matrices from the Engelbreth-Holm-Swarm tumour (BM-matrigel) do not spread, and they maintain their differentiated phenotype, most notably the heavy pigmentation. Maintenance of the differentiated phenotype by RPE cells on BM matrigel is promoted not only by the biochemical composition of the gel but also by its mechanical properties, i.e., its low rigidity prevents cell spreading. In this report, RPE cells on BM-matrigel were treated with 12-O-tetradecanoyl phorbol-13-acetate (TPA) to promote the transformed phenotype and diminish cell traction. In contrast to most cell types TPA treatment induced RPE cells to increase their spread area. TPA promoted RPE cell spreading on BM-matrigel and changed the spatial organization of actin and actin-associated proteins in the cytoskeleton-ECM linkage complexes, uncoupling actin from its extracellular counterpart. TPA did not affect other components of the cytoskeleton in RPE cells. TPA also affected labile adhesions i.e., focal contacts and adherens junctions in statu nascendi, but preformed, stable adherens junctions were resistant to TPA. TPA enhanced proliferation, blocked melanogenesis and thus inhibited differentiation of RPE cells grown on either artificial substrata or their natural basement membrane. PMID- 2194873 TI - V-K-ras transformation induces reversion to an earlier developmental form in adult rat adrenal cells. AB - The basis for specific changes in differentiation that accompany ras-oncogene mediated transformation are not understood. When short-term cultures of fibroblast-like cells from adult rat adrenal glands were transformed with Kirsten murine sarcoma virus (KiMSV), the original stromal characteristics of the target cells (metachromatic extracellular matrix, high collagen production, collagen incorporation into pericellular matrix and a fibroblastic morphology and growth pattern) diminished. In contrast, parenchymal differentiation markers (neutral lipid, delta 5, 3 beta-hydroxysteroid dehydrogenase, 21-hydroxylase and epithelial morphology) were enhanced. These changes in differentiation were initiated concurrently with the over-expression of the transforming protein v p21, but were unrelated to the levels of v-p21 expression. They were independent of the immortalizing component of transformation mediated by v-K-ras, because they did not take place in spontaneously immortalized lines derived from the same target cells, unless the lines were also transformed with KiMSV. In normal embryonic development, stromal and parenchymal adrenocortical cells arise by divergent differentiation pathways from a common, multipotential mesenchymal precursor. The transformation-induced modulation from a predominantly stromal to a more-parenchymal phenotype is thus reminiscent of reversion to a more primitive, bipotential developmental stage. PMID- 2194874 TI - [Rheumatoid arthritis of senile onset. Clinical aspects and current therapeutic data]. PMID- 2194875 TI - [Rehabilitation in cardiology]. PMID- 2194876 TI - [Antibiotics in pregnancy]. PMID- 2194877 TI - [Does Helicobacter pylori have a direct proteolytic effect in ulcerative disease?]. AB - Helicobacter pylori (H.p.), has been shown, experimentally, to exert a proteolytic activity against mucous fractions. Aim of this study was to assess the prevalence of H.p. in peptic ulcer and to analyze its possible influence on gastric mucus components, on peptic activity in gastric juice and the possible action on peptic secretion. 223 patients undergoing upper gastrointestinal endoscopy were analyzed for the presence of H.p. in the mucosa: 99 duodenal ulcer patients (D.U.), 58 gastric ulcer patients (D.U.) and 66 dyspeptic subjects. In each patients, three contiguous gastric biopsies were taken at the antrum: the first was evaluated for gastritis (Whitehead Criteria), the two other analyzed for H.p. with a rapid urease test. In a subgroup of 25 D.U. and 18 G.U. patients, two other biopsies were taken at the fundus corpus of the stomach, to evaluate peptic secretion. To determinate mucous components (acid and neutral glycoproteins, galactose and N-acetylneuraminic acid), gastric juice samples were collected during endoscopy. H.p. was present in 89% of antral biopsies in D.U., in 56% of G.U. and in 51% of D., and was associated to antral gastritis. As regard gastric juice components, we observed an increase and a decrease of acid glycoproteins, respectively, in D.U. and G.U. patients with H.p. infection. An increase of peptic activity has been found in the gastric juice of both gastric and duodenal ulcer patients H.p. positive (G.U. p less than 0.05). On the contrary, no significant differences were observed on peptic activity in the fundus-corpus biopsies between H.p. positive and H.p. negative patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2194878 TI - [Oral galactose tolerance test in the study of glucose metabolism disorders in patients with liver disease]. AB - Patients with chronic liver disease (CLD) may show an abnormal glucose tolerance test (GTT). On the other hand, it is debated whether diabetics may undergo abnormalities of liver function. The aim of our study was to see whether galactose tolerance test (GaTT) is a suitable complementary diagnostic tool in defining the glucose metabolism abnormalities characteristic of the two above mentioned clinical entities. Thirty-one patients with CLD, 16 adult diabetics and 12 healthy volunteers were considered. GTT with radioimmunoassay of plasmatic insulin (IRI) and oral GaTT were performed. CLD patients were divided into two groups: with IRI/glycemia greater than 0.4 or less than 0.4. On GaTT, galactosemia was significantly raised in CLD compared to diabetics and control. Further, a statistically significant difference was shown in the glycemic variations during GaTT between diabetics and both CLD groups. A significantly inverse ratio galactosemia/glycemia occurred during GaTT and showed a different pattern between diabetics and CLD patients with impaired insulin secretion. A careful study of galactosemia and glycemia variations during GaTT reliably defines the different patterns of glucose metabolism derangement in CLD with abnormal GTT and in diabetics. PMID- 2194879 TI - [Acute hybrid leukemia. Review of the literature and presentation of a case]. AB - In the last years, the development of immunophenotypic and molecular analyses allowed to recognize several cases of hybrid acute leukemia (AL), whose blast cell display both lymphoid and myeloid features. Hybrid, or mixed-lineage, AL seems to have distinct clinical manifestations and hematological findings, and is mainly characterized by resistance to chemotherapy and poor prognosis. We report on a patient with AL, which showed a very rapid switch from the lymphoblastic phenotype exhibited at presentation to a myelomonoblastic one, appeared at first relapse, and lastly progressed to an undifferentiated leukemia in the terminal phase. Together with this morphologic and cytochemical evolution, leukemic cells expressed, besides the primary early-B antigens, new immunological markers related to T-lymphocytic and myeloid lineages. Based on this observation and current understanding of the ontogenesis of hematologic malignancies, we discuss biological mechanisms which are likely to underlie hybrid leukemia. PMID- 2194880 TI - [Immune dysregulation in chronic tuberculosis]. PMID- 2194881 TI - [Value and limits of arterial pressure monitoring in the evaluation of the effectiveness of antihypertensive agents]. PMID- 2194882 TI - [Medical specialties. Role of educational institutions and health institutions]. PMID- 2194883 TI - [An unfinished culture, or diarrhea has its own history]. PMID- 2194884 TI - [Presence of specific factors in mother's milk against strains of diarrhea causing Escherichia coli in humans]. AB - Presence of specific secretory immunoglobulin A (sIgA) against pathogenic factors of Escherichia coli related with diarrheal disease was studied in colostrum and breast-milk samples obtained longitudinally from a cohort of rural Mexican women. Levels of sIgA against heat-labile enterotoxin, Shiga-like toxin, colonization factors antigens I, II and E8775 and adherence to HEp-2 cells were detected in samples obtained from 54 rural women during the first year of lactation. Although production of specific sIgA against these pathogenic factors was almost universal it was not constant, even in the same woman. The results reflect a definite mother-infant relationship during this period. The data support the thesis of using breast-milk as a vaccination vehicle against diarrhea associated with specific organisms during the first year of life of infants born in developing areas of the world. PMID- 2194885 TI - [Persistent hiccup: causes, diagnosis and treatment]. AB - Hiccup is a common phenomenon produced by the activation of a primitive reflex, which has its own center in the central nervous system. Most episodes last only a few minutes and are self-limited, but hiccup can get persistent and become a real problem for physician and patient alike. The center of hiccup may be activated by a great variety of stimuli travelling along different nerve path ways and bring different effector responses. Causes of hiccup are various and merit a systematic study of any patient with persistent hiccup. PMID- 2194886 TI - [Corvisart in Mexico]. PMID- 2194887 TI - [Introduction of Lister's antisepsis in Mexico in 1872]. PMID- 2194888 TI - [Rheumatic cardiopathy at the present time]. PMID- 2194889 TI - [Endoscopic ultrasonic diagnosis and cancer of the esophagus. Results of a prospective comparative study with x-ray computed tomography in 51 surgically treated patients]. AB - To investigate whether endoscopic ultrasonography could improve the preoperative staging of esophageal carcinoma we prospectively studied 56 tumors in 51 patients between March 1987 an March 1988. The results for assessing local and regional extension and preoperative staging were compared with those of computed tomography, surgery, and pathological findings. When the procedure was complete (n = 25) the accuracy of parietal spread assessment was 85.7 percent; sensitivity for nodal involvement was 83.3 percent versus 50 percent for computed tomography with an accuracy of 97.6 percent versus 96.4 percent; the discrimination between superficial and advanced cancer was 100 percent; the accuracy for preoperative staging using the Japanese classification was 84 percent. When the procedure was not complete (stenosis), endoscopic ultrasonography was complementary to computed tomography: local invasion of anatomical structures (n = 16) was better assessed by combined endoscopic ultrasonography and computed tomography (n = 11) than by endoscopic ultrasonography (n = 8) or computed tomography (n = 6) alone. We conclude that endoscopic ultrasonography is the best procedure for staging esophageal carcinoma without stenosis; further miniaturization of the transducer is necessary to improve results in the case of narrow stenosis. PMID- 2194891 TI - [Retrorectal tumor in adults. Combination of computed tomography and endorectal echography]. AB - A retrorectal tumor was identified by presacral palpation in a 41-year old woman. Combined preoperative computed tomography and intrarectal ultrasound accurately delineated regional and local spread, respectively. This combined approach confirmed diagnosis and provided guidance for total ablation of a mature cystic teratoma. PMID- 2194890 TI - [Consequences of hyperglycemia on glucose and nitrogen metabolism in liver cirrhosis. A study using a hyperglycemic clamp]. AB - To study the consequences of hyperglycemia on glucose and nitrogen metabolism in cirrhosis, an hyperglycemic clamp was performed in 5 cirrhotic patients and 5 normal controls during two subsequent periods of 90 min, at 7.78 and then at 13.89 mmol/l. In the first period, glucose infusion and metabolic clearance rates were decreased in cirrhotics vs controls (p less than 0.05). In the second period, this difference between the two groups disappeared because of a more important enhancement in cirrhotics. Baseline plasma C peptide levels and those during hyperglycemia were the same during hyperglycemia in both groups, but plasma insulin level rose more in cirrhotics (p less than 0.05). Baseline insulin secretion following IV glucagon was reduced in cirrhotics vs controls (p less than 0.05), but became normal in the hyperglycemic state. Plasma glucagon levels were enhanced at all times in cirrhotics vs controls (p less than 0.01), but dropped more in cirrhotics vs controls (p less than 0.05). Insulin responsiveness, defined as the "glucose consumption: plasma insulin concentration" ratio was reduced in cirrhotics at 7.78 mmol/l (p less than 0.01), but was the same in both groups at 13.80 mmol/l because of a more important enhancement in cirrhotics, reflecting an improvement of insulin action probably at the post-receptor level and of non-insulin-mediated glucose transport. Hyperglycemia induced a drop in plasma concentration and muscular release of all aminoacids, excepted alanine, between the basal state and the end of the study. Aminoacid concentration rose only in cirrhotics, without any change in muscular output. In the same time, blood ammonia level rose only in cirrhotics, without reduction of muscular uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2194892 TI - [Complicated anal fistula: contribution of endoscopic ultrasonic diagnosis]. PMID- 2194893 TI - The mucoid cap over superficial gastric damage in the rat. A high-pH microenvironment dissipated by nonsteroidal antiinflammatory drugs and endothelin. AB - The ability of the "mucoid cap" of mucus, fibrin, and cellular debris that forms over sites of superficial gastric damage to provide a relatively high-pH microenvironment was investigated in the rat. Furthermore, the effects of administration of nonsteroidal antiinflammatory drugs or reduction of mucosal blood flow on this microenvironment were investigated. Superficial mucosal damage induced by a 2-minute exposure to hypertonic saline produces a mucoid cap that has a pH of 4-6 despite the presence in the lumen of a solution of acid with a pH of less than 1. This relatively high-pH microenvironment remained even when the exposure to 0.15-mol/L HCl was continued for as long as 1 hour. Intraperitoneal administration of indomethacin (5 mg/kg) or naproxen (10 mg/kg) resulted, within 10-25 minutes, in complete dissipation of this high-pH microenvironment, with the subsequent development of hemorrhagic erosions. These effects of indomethacin and naproxen occurred subsequent to significant inhibition of gastric prostaglandin synthesis by these agents. Rapid dissipation of the pH gradient could also be produced by brief (30-second) clamping of the arterial blood supply to the chambered mucosa or by systemic administration of a vasoconstrictor (endothelin 1), in both cases resulting in the development of hemorrhagic erosions. These results show that the mucoid cap over sites of superficial damage provides a relatively high-pH microenvironment and that dissipation of this microenvironment by inhibitors of prostaglandin synthesis or by reduction of mucosal blood flow can convert sites of superficial mucosal injury to hemorrhagic erosions. Such inhibitory effects might contribute to the ulcerogenic actions of nonsteroidal antiinflammatory drugs. PMID- 2194894 TI - Intragastric balloon in the treatment of super-morbid obesity. Double-blind, sham controlled, crossover evaluation of 500-milliliter balloon. AB - A prolonged randomized, prospective, double-blind, crossover study, including a sham-sham-treated group, was undertaken to evaluate the efficacy and safety of a 500-mL gastric bubble (Ballobes; DOT ApS, Rodovre, Denmark) as an adjunct to diet, physical training, and behavioral modification. Only supermorbidly obese patients who fulfilled the usual criteria for surgery were admitted. A weight loss of 38 kg in the first 17 weeks and another 12 kg in the second 18 weeks could be achieved. The body mass index, the percentage of overweight and the loss in percentage of initial weight, paralleled this impressive weight loss. In the second period, a plateau effect occurred after the massive changes in the first period, and only one third of the changes in all parameters was seen. Stratification into a sham-sham, sham-balloon, balloon-sham, and balloon-balloon group did not show any statistical difference for all parameters between the four groups. The double-blind nature of the study was affirmed by the patient's correct judgment of the presence or absence of a balloon in only 21% of the balloon and 44% of the sham procedures. Gastrointestinal complications were infrequent and consisted of erosions (three patients), asymptomatic reflux oesophagitis (one patient), and asymptomatic gastric ulcer (one patient). Only the latter patient had elevated gastrin levels. One patient could not tolerate the balloon. All balloons remained airtight during both parts of the study for a mean of 123 days. This study confirmed the safety of the balloon, but no additional benefit could be ascribed to the balloon compared with a very low calorie diet and medical and dietary support. PMID- 2194895 TI - Secretory immunity in celiac disease: cellular expression of immunoglobulin A subclass and joining chain. AB - Two-color immunofluorescence staining in situ demonstrated increased proportions of immunoglobulin A2 subclass-producing cells in jejunal mucosa from adult patients with untreated (47%, P less than 0.01) or treated (37%, P less than 0.05) celiac disease compared with controls (28%). Costaining was also performed for joining chain, which is a key factor in the epithelial transport of secretory antibodies; its expression by immunoglobulin A2 cells was only marginally reduced in untreated patients (96%) compared with treated patients and controls (98%). Also, immunoglobulin A1 cells showed similar joining chain positivity (89%) in all three groups. Considering the expanded total jejunal immunoglobulin A-cell population and the subclass-associated joining chain expression, it could be calculated that the potential of immunoglobulin A2 cells for contribution to secretory immunity was increased 3.9 times in untreated (P less than 0.01) and 1.8 times in treated (P less than 0.05) patients and that of immunoglobulin A1 cells was increased 1.7 times in untreated (P less than 0.05) but remained unaltered in treated patients. The estimated relative contributions of locally produced immunoglobulin A2 to secretory immunoglobulin A would thus be 51% and 37% in the two patient categories, respectively, compared with 31% in the controls. These data suggested enhanced secretory immunity in celiac disease and might reflect a protective, possibly antimicrobial, immune response. It could not be excluded, however, that increased generation of secretory immunoglobulin A at the same time contributes to the gluten-induced pathogenesis of celiac disease. PMID- 2194896 TI - c-Ki-ras mutations in chronic ulcerative colitis and sporadic colon carcinoma. AB - Mutations in the first exon of the c-Ki-ras protooncogene were analyzed in carcinomas and dysplasias from patients with sporadic colon cancer and chronic ulcerative colitis by a combination of histological enrichment, cell sorting, polymerase catalyzed chain reaction, and direct sequencing. In contrast to sporadic colon carcinomas, where 52% (11 of 21) contained mutations in codon 12, only 1 of 28 samples of ulcerative colitis associated carcinoma or dysplasia contained a c-Ki-ras mutation, despite the presence of aneuploid cell populations. These results suggest that a different genetic pathway for tumor progression may exist between sporadic colon carcinoma and carcinomas arising in chronic ulcerative colitis. PMID- 2194898 TI - Hemoccult test and colorectal cancer. PMID- 2194897 TI - Regulation of cholesterol metabolism in the intestine. AB - The small intestine is a major site of cholesterol biosynthesis and lipoprotein degradation. It is also the organ responsible for absorbing dietary and endogenously produced biliary cholesterol. Cholesterol metabolism in the intestine is regulated by factors that will alter cellular cholesterol requirements. Thus, during increased cholesterol flux, which occurs by bile acid faciliated cholesterol absorption or by lipoprotein-mediated uptake of cholesterol, cholesterol synthetic rates decrease and esterification rates increase. The mechanisms by which dietary fats regulate intestinal cholesterol metabolism are complex. Dietary fats alter membrane fatty acid composition. Simultaneously, they also promote lipoprotein secretion and alter cholesterol absorption. Intestinal 3-hydroxyl-3-methylglutaryl coenzyme. A reductase activity is regulated by enzyme phosphorylation-dephosphorylation. The regulation of acylcoenzyme A-cholesterol acyltransferase activity by this mechanism remains controversial. Data on hormone regulation of intestinal cholesterol metabolism are not conclusive, although progesterone seems to be a potent inhibitor of acylcoenzyme A-cholesterol acyltransferase activity in intestinal cell culture and isolated cells. In a manner similar to the regulation of cholesterol metabolism in other cells, the enterocyte responds appropriately to factors that alter cholesterol flux. Therefore, changes that occur in the rates of cholesterol synthesis and esterification will reflect the cholesterol requirements of the cell. PMID- 2194899 TI - A controlled study of therapeutic endoscopy for peptic ulcer with non-bleeding visible vessel. AB - In a period of 14 months, a prospective, randomized, controlled trial was undertaken in 61 patients who had bled from peptic ulcers in which, at endoscopy, non-bleeding vessels were visible in the ulcer crater. The control group consisted of 31 patients in whom the procedure was limited to observation alone; in 30 patients the ulcer base was coagulated by means of a heat probe. There were no statistically significant differences between the two groups in the rate of rebleeding, the assurance of ultimate hemostasis, the volume of blood transfusion required, the duration of hospitalization, or eventual mortality. However, the need for emergency surgical intervention was less frequent in the heat probe group (2 of 30) than among the controls (9 of 31) (p = 0.0243). Moreover, in the treatment group, those patients of advanced age (greater than 60 years), in shock, requiring blood transfusion of greater than 500 ml, and in whom blood or coffee ground material was seen in the stomach, thermocoagulation achieved statistically more effective hemostasis than that observed in the control group. For these high-risk subsets of patients with non-bleeding visible vessels, we recommend heat probe coagulation rather than mere observation. PMID- 2194900 TI - A controlled study of human resting gastric mucosal blood flow by endoscopic laser-Doppler flowmetry. AB - We investigated regional variation in resting focal gastric mucosal blood flow obtained by endoscopic laser-Doppler flowmetry in patients with symptoms of dyspepsia or peptic ulcer (N = 12) and asymptomatic healthy volunteers (N = 6). Mucosal blood flow was measured for 1 min at the duodenum (first part), prepylorus, antrum and body (anterior and posterior walls), angularis, mid greater curvature, fundus, and distal esophagus. At all sites, mean +/- SE blood flow in patients was 71.88% of the corresponding value in volunteers (1.15 +/- 0.10 and 1.60 +/- 0.13 volts, p less than 0.02, t test). In both groups, blood flow was highest in the fundus, followed by the body and lowest in the antrum; the angularis had a high blood flow, second only to the fundus. There was no correlation between age and blood flow. We conclude that regional variation in resting gastric mucosal blood flow exists in health and disease. PMID- 2194901 TI - Prospective randomized study of Maloney esophageal dilation--blinded versus fluoroscopic guidance. AB - Controversy exists over the need for fluoroscopic guidance when performing Maloney esophageal dilation. This prospective randomized single-blinded study evaluated the safety and efficacy of blinded and fluoroscopic technique. A total of 162 dilations were performed in 43 patients with benign esophageal strictures referred for maintenance dilation, 88 randomized to blinded technique, and 74 to fluoroscopic guidance. Use of fluoroscopic guidance resulted in a higher rate of successful dilations than the blinded technique (96% vs. 80%, p less than 0.05) and greater operator accuracy in assessing success of dilation (98.6% vs. 85%, p less than 0.05). Although adverse events (such as passage into trachea, gross hematemesis, impaction in a hiatal hernia) occurred more often with blinded technique (11.3% vs. 5.4%), this difference did not reach statistical significance. However, recognition of adverse events was significantly greater with fluoroscopic guidance than with the blinded technique (100% vs. 20%, p less than 0.05). No difference existed between groups regarding speed of dilation, patient comfort, or blood on the dilator. Patients were unreliable in their assessment of dilation success. Fluoroscopic guidance is recommended when performing Maloney dilation. PMID- 2194902 TI - A single procedure endoscopic technique for replacing partially extruded percutaneous endoscopic gastrotomy tubes. PMID- 2194903 TI - Endoscopic removal of prolene sutures from the common bile duct during endoscopic retrograde cholangiography. PMID- 2194904 TI - Carcinoid tumor complicating ulcerative colitis. PMID- 2194905 TI - Strokes and the carotid: myths and realities. AB - Cervical bruits in asymptomatic individuals identify persons at increased risk of future stroke and at even higher risk of ischemic heart disease. Strokes in these patients rarely occur in the same vascular distribution as the bruit. In prospective studies, an asymptomatic bruit does not identify patients at higher risk of perioperative stroke even in patients undergoing coronary bypass or other major vascular surgery. When a stroke occurs in the perioperative setting, it is much more likely due to embolism from the cross-clamped aorta or extraneous material from the bypass machine than from hypoperfusion of, or embolism from, the carotid arteries. PMID- 2194906 TI - Autonomic neuropathy: clinical presentation and differential diagnosis. AB - Autonomic neuropathy (AN) may occur in the elderly in connection with other common illnesses afflicting this age group, such as diabetes or Parkinson's disease, or even as the primary illness. Symptoms of AN are numerous, but syncope, with its risk for fractures and head trauma, is the most serious. The clinical presentation and differential diagnosis of AN are discussed, as are a group of diseases associated with AN. Treatment guidelines are outlined. PMID- 2194907 TI - Update on diabetic nephropathy in NIDDM. AB - Diabetic nephropathy is an important clinical entity in the geriatric population. One half of newly enrolled patients in dialysis programs have non-insulin dependent diabetes mellitus (NIDDM), and the number of NIDDM patients with chronic renal insufficiency is estimated to be eight times greater than those with insulin-dependent diabetes mellitus. In view of this growth potential, this paper is intended to briefly review the epidemiology and pathogenesis of diabetic nephropathy, and to highlight some important considerations in the clinical evaluation and treatment of patients with NIDDM. PMID- 2194908 TI - Non-melanomatous skin cancer in the elderly: diagnosis and management. AB - Non-melanomatous skin cancers, particularly basal cell and squamous cell carcinomas, are frequently observed in elderly persons and are primarily the result of the chronic, cumulative effects of exposure to sunlight (ultraviolet light radiation). Characteristics of both types of neoplasm and diagnosis and management of non-melanomatous skin cancer are reviewed. Treatment based on multiple factors, including patient age, overall health status, histologic pattern, and cosmetic considerations, is described. PMID- 2194909 TI - [Endocrine surgery in pregnancy]. PMID- 2194910 TI - [Heart surgery in pregnancy]. PMID- 2194911 TI - [Acute abdomen in pregnancy. A review]. PMID- 2194912 TI - [Pregnancy and myomas--when operate?]. PMID- 2194913 TI - [Hysterectomy in cesarean section. Indications and complications]. PMID- 2194915 TI - [Surgical treatment of malignant diseases in pregnancy (cervix, ovary, breast, lymphoma)]. PMID- 2194914 TI - [Trauma and pregnancy]. PMID- 2194916 TI - [Treatment of obstructive diseases of the efferent urinary tract in pregnancy]. PMID- 2194917 TI - [Surgical abdominal diseases in pregnancy]. PMID- 2194918 TI - National health line. PMID- 2194919 TI - [Caution in computer reliability. 4. Expert systems--artificial intelligence- computer critique]. PMID- 2194920 TI - [Identification of a specific protein in flat revertant cell lines derived from ras oncogene-transformed cells]. AB - Total proteins from a mouse embryo fibroblast cell line NIH/3T3, NIH/3T3 cells transformed by human activated c-Ha-ras (EJ-ras) oncogene (EJ-NIH/3T3), and the two flat revertant cell lines, R1 and R2 were analyzed by two-dimensional gel electrophoresis (IEF and NEPHGE). Several hundred polypeptides were resolved as seen by silver staining. Common alterations in four polypeptide spots were observed in the revertants when compared with NIH/3T3 and EJ-NIH/3T3 cells. In these alterations, a new polypeptide spot p92-5.7 (designated by molecular weight X 10(-3) and pI) was detected only in the revertants, but not in NIH/3T3 and EJ NIH/3T3 cells. Furthermore, the expression level of p92-5.7 seemed to be associated with the flat morphology and the reduced tumorigenicity of the revertants. The polypeptide p92-5.7 was also not detected in the total proteins extracted from BALB/3T3 cells, NIH Swiss mouse primary embryo fibroblasts. Subcellular fractionation of total protein from R1 cells revealed that the p92 5.7 was present in the cytosol. The p92-5.7 was not phosphorylated in the steady state of R1 cells. Western blot analysis using an anti-gelsolin antibody demonstrated that the p92-5.7 might be a variant form of gelsolin which is thought to be an actin regulatory protein or a gelsolin-like polypeptide. The expressions of gelsolin mRNA in the revertants were higher than in the EJ-NIH/3T3 cells. These results may suggest that the expression of p92-5.7 detected only in the revertants is associated, at least in part, with the reversion. This may be the first demonstration of the specific protein expression in the flat revertants. PMID- 2194921 TI - Liver function and pharmacological considerations in pathogenesis and treatment of portal hypertension. PMID- 2194922 TI - Depressed liver regeneration after partial hepatectomy of germ-free, athymic and lipopolysaccharide-resistant mice. AB - A hypothesis has been proposed by this laboratory that endogenous gut-derived lipopolysaccharide is responsible for systemic endotoxemia in animals with acute liver injury particularly after partial (67%) hepatectomy. Systemic lipopolysaccharide and possibly fibrin aggregates or tissue debris then elicit release of cytokines from phagocytizing macrophages and/or monocytes that may be essential for normal liver regeneration. To test this hypothesis liver regeneration was assessed in germ-free euthymic mice that lack the gram-negative bacterial source of lipopolysaccharide, as well as being deficient in lymphoid tissue and relatively resistant to endotoxin. To complement the germ-free animals, conventional athymic nude BALB/c mice and conventional lipopolysaccharide-resistant C3H/HeJ mice were also examined. Liver regeneration, quantified by [3H] thymidine incorporation into hepatic DNA after partial hepatectomy was performed on mice anesthetized with ether, was significantly depressed in germ-free euthymic and conventional athymic BALB/c mice and delayed in conventional lipopolysaccharide-resistant C3H/HeJ mice, as compared with conventional control BALB/c and C3H/HeN animals. Pretreatment of conventional euthymic control mice with lipopolysaccharide 24 hr before surgery significantly stimulated hepatic DNA synthesis after 67% liver resection. Germ-free euthymic, conventional athymic, and conventional lipopolysaccharide-resistant mice pretreated with endotoxin did not manifest significant stimulation of liver regeneration. Evidence is reviewed that cytokine release in response to endotoxin was depressed in germ-free euthymic, conventional athymic, and conventional lipopolysaccharide-resistant mice as compared with conventional euthymic controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2194923 TI - Effects of branched-chain amino acids on nitrogen metabolism in patients with cirrhosis. AB - This study was conducted to determine whether an amino acid solution enriched with branched-chain amino acids altered protein catabolic rates and plasma ammonia in patients with cirrhosis. Nine stable subjects were given two peripheral intravenous infusions: a standard amino acid solution (solution A) and a branched-chain-enriched solution containing 97% more leucine (solution B). Each solution was given for separate 9-day (group 1, n = 6) or 3-day (group 2, n = 3) periods. Amino acid solutions delivered 0.7 gm protein.kg-1.day-1. Diets provided an additional 0.3 gm protein plus maintenance calories. Protein turnover was assessed by a primed continuous infusion of [1-14C] leucine in six patients (three patients in group 1 and three patients in group 2). Nitrogen balance and urinary 3-methyl histidine excretion were determined in group 1 patients. Compared with solution A, solution B increased leucine flux and leucine oxidation but had no significant effect on protein synthesis or catabolism based on the plasma specific activity of either leucine or alpha-ketoisocaproic acid. The additional leucine infused with solution B was quantitatively oxidized. Nitrogen balance did not differ with the two solutions and there was also no difference in the urinary excretion of 3-methyl histidine, suggesting that muscle protein catabolism was unchanged. Plasma ammonia concentration decreased significantly during the infusion of solution B and was associated with a slight fall in plasma glucagon concentration. The results indicated that a branched-chain-enriched amino acid solution did not alter protein synthesis or catabolism although it did lower the plasma ammonia when compared with a standard amino acid formula in stable cirrhotic patients. PMID- 2194924 TI - Hepatic vein thrombosis in Behcet's disease. AB - We describe four patients with hepatic vein thrombosis caused by Behcet's disease and review the 17 previously published cases. In addition, we compared these 21 cases of hepatic vein thrombosis to our 24 cases of hepatic vein thrombosis caused by primary myeloproliferative disorders. In patients with Behcet's disease, a male predominance (male/female ratio, 19:1) contrasted with the female predominance found in patients with hepatic vein thrombosis complicating primary myeloproliferative disorders (sex ratio = 1:3). The mean age at clinical onset was younger in patients with Behcet's disease than in those with primary myeloproliferative disorders (29 vs. 35 yr). Obstruction of the inferior vena cava was found in 90% of patients with hepatic vein thrombosis caused by Behcet's disease. Inferior vena caval thrombosis appears to be the main pathophysiological mechanism of hepatic vein thrombosis in patients with Behcet's disease. Unlike patients with primary myeloproliferative disorders who often had a progressive course, one third of patients with Behcet's disease had acute liver failure and died within 2 wk of clinical onset. These findings suggest that, in patients with Behcet's disease, hepatic vein thrombosis is a sudden event usually related to the extension of a caval thrombus to the ostium of the hepatic veins. PMID- 2194925 TI - Vasoactive intestinal polypeptide-like immunoreactivity during reproduction in doves: influence of experience and number of offspring. AB - To assess the possibility that vasoactive intestinal polypeptide (VIP) plays a role in naturally occurring changes in prolactin secretion in ring doves, we used immunohistochemical techniques to measure VIP-like immunoreactivity in the brain as a function of stage of the reproductive cycle. Differences between parental and nonparental birds in VIP profiles were detected in the ventral portion of the infundibular region. More specifically, there is an increase in cell size and staining intensity in the ventral infundibulum of breeding birds compared to simultaneously processed tissue taken from control animals. In both sexes, an increase in size of VIP-like immunoreactive cells is detectable during courtship and early incubation, anticipating the increase in plasma prolactin levels. VIP cell size remains elevated from about Incubation Day 14 to Brooding Day 14, and a steady decrease is observed during the remaining posthatching period, as squab begin to feed independently. Compared to parents rearing one squab, those with two young have a prolonged interval of increased infundibular VIP immunoreactivity. Furthermore, doves with no previous experience of a breeding cycle exhibit prolonged VIP-like immunoreactivity compared to experienced parents, paralleling previously described differences between these groups in parental behavior. PMID- 2194926 TI - Neuroendocrine, behavioral, and morphological changes associated with the termination of the reproductive period in a natural population of male rough skinned newts (Taricha granulosa). AB - Male rough-skinned newts (Taricha granulosa) were collected from the same natural population every second week from early April to mid-June. They were either field tested for their sexual responsiveness or used to measure the plasma concentrations of androgens and corticosterone, the brain concentrations of immunoreactive (ir) gonadotropin-releasing hormone (GnRH) and arginine vasotocin (AVT), and morphological parameters. During the experimental period, the percentage of sexually responsive males gradually declined from 100 to 4%, concurrent with a decrease of plasma concentrations of androgens, but not corticosterone. Concentrations of irGnRH in two brain regions (medial septum; ventral telencephalon containing the nervus terminalis) did not change significantly during this time. In the infundibulum, irGnRH concentrations increased from the end of May to mid-June, which coincided with an increase in plasma androgen concentrations, a marked increase in testis weights, and a decrease of the proportion of males with spermatozoa in their vas deferens. During this period, no changes in irAVT concentrations in four brain regions (infundibulum; pars distalis of the pituitary; interpeduncular nucleus; cerebrospinal fluid) were detected, but significant changes were observed for irAVT in the dorsal preoptic area that were not correlated with the seasonal changes in behavior. Also, during this period, there were decreases in mean body weight and tail height, and in the proportion of males with smooth skin and dark nuptial pads. These results are discussed in view of our current knowledge of the endocrine mechanisms that regulate sexual behaviors and secondary sex characteristics in male amphibians. PMID- 2194927 TI - Sleep disorders of older people: report of a consensus conference. PMID- 2194928 TI - Research design clarified. PMID- 2194930 TI - Deciduous dentition of a Late Archaic population of Ohio. AB - I describe the developmental, metric, morphologic, and pathologic features of deciduous dentition in a terminal Late Archaic (c. 3000 B.P.) Native American population in Ohio. Development of deciduous dentition in this Late Archaic population is stable with little sequence variation. The pattern of development (ldc, ldp3, ldp4) cannot be shown to be different from a modern Euro-American sample. There is an indication, however, that the permanent first molar in the Late Archaic population developed somewhat more rapidly with respect to the deciduous teeth than in the Euro-American sample. Metric and morphologic features of deciduous dentition in the Late Archaic population appear typical for a population of northeast Asian descent. In general, these metric and morphologic features are shown to be useful in distinguishing among populations of differing ancestries. Developmental and acquired pathologic conditions of deciduous dentition are rare or absent in the Late Archaic population. Absence of linear enamel hypoplasia indicates sufficient access to basic resources for the younger children of this population, and the low frequency of caries reflects the relatively cariogenic-free nature of the diet of these hunter-gatherers. PMID- 2194929 TI - Population structure of the Peljesac Peninsula, Yugoslavia. AB - We gathered serogenetic and parent-offspring migration data from 604 residents of 7 villages on the Peljesac peninsula in southern Yugoslavia. A variety of population genetics and multivariate statistics models and procedures give a concordant picture of the population structure of this region. Extensive migration is the dominant microevolutionary force patterning the variation seen today. Multiple population bottlenecks have also occurred over the past few centuries as a result of disease, famine, war, economic failure, and founder events, making it likely that genetic drift has been an important factor in the history of this population system. PMID- 2194931 TI - [Purification and identification of antimicrobial peptides of rabbit neutrophils]. AB - Five antimicrobial peptides were extracted from the cytoplasmic granules of rabbit neutrophils with 0.01 mol/L citric acid. SDS-PAGE gel densitometric analysis of the citric acid extract showed that they accounted for 34%-42% of the total extract proteins. When subjected to acid urea polyacrylamide gel electrophoresis, five peptides migrated much further to the cathode than lysozyme. Beginning with the most cathodal component, they were in turn referred to as NP1, NP2, NP3, NP4, and NP5. They were purified from the citric acid extract by virtue of preparative polyacrylamide gel electrophoresis. Each of them was of low molecular weight (2,500-6,000) as determined by SDS-PAGE. Three of the peptides were tested in vitro for fungicidal activity. When Candida albicans (10(7)/ml) were incubated with 12.5 micrograms/ml of NP1 or NP2 at 37 degrees C for 2 h, the death rates of the organisms were 96.6% and 93.3% respectively. NP3 was shown to be active against Candida albicans although less potent than NP1 and NP2. PMID- 2194932 TI - [Sampling survey of mentally deficient people in Sichuan]. AB - From first April to 15th May 1987, 145,201 people were investigated by using the ways of layer, equal probability and mass sampling. Two thousand three hundred and forty two of them were confirmed to be mentally deficient. The incidence was 16.13%. It was estimated that 1,665,000 people have mental deficiency in Sichuan. The estimated range of reliability of 95% was 1,528,000-1,801,000. One million and three hundred ninety three thousand of them only had mental deficiency, while 272,000 had other organic deficiency. Male:female ratio was 101.4:100. The incidence of 6-14 year-old was 38.14%, which was 3 times higher than that of other age groups. Mild mental deficiency was 16.4 times more than severe mental deficiency. The most common causes were hereditary diseases, encephalitis, malnutrition, cerebral trauma, pregnant diseases, etc. All of the causes belonged to preventable diseases. PMID- 2194933 TI - [Differential diagnosis of parotid gland masses by gray scale real-time ultrasound]. AB - This paper reports the ultrasonographic diagnoses in 18 cases of parotid gland masses confirmed by surgery and biopsy and pathology. The diagnostic accuracy was 100% (18/18) in the judgement in locations and was 72% (13/18) in the judgement in the nature of the disease. The clinical value of ultrasonographic diagnosis in parotid gland masses and the features of the sonographic images in benign and malignant tumors were analysed and discussed. PMID- 2194934 TI - The ability of mouse monoclonal antibodies to direct the cytotoxic function of cytokine-activated human eosinophils. PMID- 2194935 TI - Increasing the validity of research results with a blend of laboratory and clinical strategies. AB - Some nursing research problems may benefit from studies that combine laboratory and clinical research settings. Examples of studies that use a blend of laboratory and clinical components are provided. Traditional laboratory, clinical, and combined laboratory-clinical research settings are discussed in terms of their relative potential for yielding valid results. PMID- 2194936 TI - [Dermatitis caused by Cheyletiella. Description of 8 cases and review of the literature]. AB - The Authors report eight cases of Cheyletiella dermatitis, parasite mite of domestic animals but also known as pathogenic for man. This animal parasitosis mentioned many times in other countries, seems to be very diffused in Italy, too. Nevertheless, the literature tells that normally, in our country, Cheyletiella dermatitis is a pathology completely underestimated and almost unknown. The Authors, because of the aspecificity of the clinical and histopathological data, lay special stress on the differential diagnosis problems concerning this infestation. PMID- 2194937 TI - [Annular granuloma in HIV positive patients]. AB - Pathogenesis of Granuloma Annulare is not resolved. In some Authors' opinion it is caused by an allergic granulomatous reaction to an unknown dermal antigen. Presence of Granuloma Annulare in patients with Human Immunodeficiency Virus (HIV) infection questions this hypothesis. We present two cases of such association and review eleven patients previously described in the literature. Clinical and histological findings suggest that the cell mediate immune response is not the dominant pathogenetic event, especially in cases of altered cell mediated immunity. PMID- 2194938 TI - [Eosinophilic pustular folliculitis. Description of a clinical case treated with PUVA therapy]. AB - We report the case of a 62 years-old Italian man affected by crops of pruritic follicular sterile papulo-pustules on the face, trunk and arms. Histopathologic examination revealed a perifollicular inflammatory cell infiltrate composed mostly of eosinophils. These features are characteristic of eosinophilic pustular folliculitis. There is not any uniformly effective treatment for this condition. In our patient the disease did not respond to dapsone, H1 antihistamines and indomethacin. Oral corticosteroids gave good results but were unsuitable for their side effects. The response to PUVA therapy was excellent. In our opinion PUVA therapy is a highly effective and safety treatment for EPF. PMID- 2194939 TI - Regulation of red cell acetylcholinesterase activity in diabetes mellitus. AB - Despite the fact that the significance of red cell membrane acetylcholinesterase (AChE) is unknown, this enzyme of red cell assumes importance since many of its properties have been found to be similar to purified enzyme form of brain tissues. Our investigations on the effect of insulin-dependent diabetes mellitus on red cell AChE revealed that the activity of this enzyme is significantly decreased in diabetes. Insulin treatment restored the activity to the normal level. Solubilization of normal, diabetic and insulin treated diabetic red cell membranes with Triton X-100 (0.2% v/v) caused a general decline in AChE activity, however the per cent decline in activity of diabetic enzyme was lower as compared to normal and insulin treated conditions. From our results it is inferred that the decreased red cell AChE activity in diabetes is due to lesser number of active enzyme molecules and also due to altered membrane microenvironment. PMID- 2194940 TI - Human renin inhibitor peptides. PMID- 2194941 TI - Concentration-effect analysis of antihypertensive drug responses. AB - It is now widely recognized that a rigid stepped-care approach to antihypertensive therapy is not universally appropriate. Individualized treatment may result in good or better blood pressure control and a simpler regimen without troublesome side effects. Successful development of such a strategy depends on accurate characterization of a dose-response relation and quantitative assessment of the response in each individual. In the past such relations have proved to be hard to identify for antihypertensive drugs, often because of inappropriate study design during drug development. Despite failure of earlier studies to identify drug concentration-antihypertensive response relations, use of concentration effect modeling, which recognizes and characterizes the temporal discrepancy between drug concentration and effect, has proved more successful. By using such approach, it has been possible to characterize the concentration-effect relations after acute and steady-state antihypertensive therapy with prazosin, doxazosin, nifedipine, verapamil, and enalapril. With enalapril and nifedipine, it has been demonstrated that the mathematical parameters of effect derived from the first dose can predict the response to these drugs after 4-6 weeks of treatment. These findings suggest that the definition of individual concentration-effect relations may be of value in the rational choice of antihypertensive drug therapy and optimization of dose and dose frequency. In particular, the approach can provide valuable information on dose-effect relations and should optimize choice of dose intervals in drug development and practice. PMID- 2194942 TI - Antirenin immunization versus angiotensin converting enzyme inhibition in rats. AB - The effects of specific active immunization against renin were compared with those of chronic angiotensin converting enzyme (ACE) inhibition. Male spontaneously hypertensive rats (SHR) were immunized (SHR-I) (n = 10) against pure murine renin (four injections of 30 micrograms/kg s.c.) or received (SHR-P) (n = 11) a converting enzyme inhibitor (perindopril, 2 mg/kg/day per os for 4 weeks). Sham-immunized SHR (SHR-S) (n = 12) and normotensive Wistar-Kyoto (WKY-S) (n = 12) rats served as controls. At 15 weeks of age, 24-hour average blood pressure was obtained in freely moving rats using intra-aortic pressure recording with computer analysis. Antirenin immunization induced high circulating titers of antibodies, a fall in plasma renin activity (-95%), and urinary excretion of mineralocorticoids. Perindopril abolished the pressor response to angiotensin I, whereas plasma ACE was only partly (-56%) decreased. It also increased plasma renin activity and did not alter the urinary excretion of steroids. Both immunization and perindopril allowed the blood pressure of SHR to return to the level of WKY-S rats and reduced the left ventricular weight. These decreases were associated with an elevated sympathetic nervous system activity as indicated by increases in the urinary excretion of catecholamines and their metabolites. It is conclude that, apart from an unaltered steroid synthesis, most of the cardiovascular effects of chronic ACE inhibition are similar to those of antirenin immunization, thus indicating that blockade of the circulating and renal renin-angiotensin system accounts for most of the effects of ACE inhibitors. PMID- 2194943 TI - Changes in gastrointestinal, pancreatic, biliary, and hepatic function with aging. AB - The understanding of "normal" aging of the gastrointestinal tract, pancreas, and hepatobiliary system is confounded by the difficulty in identifying healthy elderly subjects for study. There appear to be predictable changes in gastric secretion and emptying, intestinal and pancreatic morphology, colorectal motility, and hepatic mass and blood flow with aging. However, the functional significance of these changes is variable. Further investigations will be necessary to resolve currently conflicting data, and validation of animal models of aging will enhance future research into these areas. PMID- 2194944 TI - Esophageal disorders in the elderly. AB - A variety of esophageal abnormalities produce the symptoms of heartburn, dysphagia, and/or chest pain in the elderly. Most such diseases also occur in younger patients, but some disorders are unique to the elderly or occur with increased frequency. Diagnostic and therapeutic approaches are discussed. PMID- 2194945 TI - Peptic ulcer disease in the elderly. AB - Peptic ulcer disease in the elderly poses challenges to the physician distinct from those encountered in younger individuals. Factors predisposing to the more aggressive natural history of peptic ulcer disease in the elderly are examined. These are of great importance in considering diagnostic investigations, the choice of therapeutic agents, and the management of complications. Despite advances in operative technique and care, surgery, particularly when emergent, is attended by a high mortality in this group. The utility of diagnostic and therapeutic endoscopy is discussed, and strategies for short and longer term medical treatment are presented. PMID- 2194946 TI - Gastritis in the elderly. AB - The elderly have an increased prevalence of gastritis and the complications associated with it. The two major classes of acute and chronic gastritis, type A and B, are discussed as they relate to clinical findings, histologic features, and pathogenesis. An age-related increase in the frequency of Helicobacter pylori (formerly Campylobacter pylori) infection in the elderly parallels the known age related increase in the prevalence of gastritis. The close association between gastritis in the elderly and hypochlorhydria and gastric carcinoma is also explored. PMID- 2194947 TI - Upper and lower gastrointestinal bleeding in the elderly. AB - Gastrointestinal bleeding in the elderly is a common problem with numerous and varied causes. Its diagnosis and treatment require a careful, systematic approach by physicians with special expertise. Under the proper circumstances, elderly patients with upper or lower gastrointestinal bleeding do well even when surgery is required, and an individual's age, by itself, should not preclude aggressive medical care. PMID- 2194948 TI - Ischemic diseases of the bowel. AB - The ischemic bowel diseases are a heterogeneous group of disorders usually seen in elderly individuals. They represent ischemic damage to different portions of the bowel and therefore produce a variety of clinical syndromes and outcomes. Proper diagnosis and management of patients with ischemic bowel disease require vigilance on the part of the physician and a willingness to embark on an aggressive plan of diagnosis and management in the appropriate setting. PMID- 2194949 TI - Diarrhea and malabsorption in the elderly. AB - Neither diarrhea nor malabsorption readily springs to mind as a major clinical problem when considering gastrointestinal disorders of the elderly. However, such disorders commonly occur in older age groups, although more covertly than in the young, and can result in disability. For this reason, it is important for the clinician to recognize these symptoms and disorders as significant and specifically to seek a history of diarrhea or evidence of malabsorption. PMID- 2194950 TI - Inflammatory bowel disease in the elderly. AB - Ulcerative colitis and Crohn's disease both may occur in the elderly. In many populations, a second peak in the incidence of inflammatory bowel disease occurs near age 70. Clinical manifestations of inflammatory bowel disease in the elderly are generally similar to those seen in younger patients, although there is a tendency for both ulcerative colitis and Crohn's disease to involve more distal segments of the gut in older patients. Ischemic and infectious colitis, diverticulitis, and malignancy can all masquerade as inflammatory bowel disease in the elderly. Recent epidemiologic and clinical reports indicate that the outlook for older patients with inflammatory bowel disease is more favorable than previously suspected. PMID- 2194951 TI - Diverticular disease in the elderly. AB - The prevalence of diverticular disease shows a striking correlation with advancing age. The spectrum of disease ranges from the entirely asymptomatic to a life-threatening surgical emergency. The diagnosis of acute diverticulitis is often particularly difficult to make in the elderly because of muted symptoms and signs. Current concepts of diagnosis and therapy are discussed. PMID- 2194952 TI - Constipation and fecal incontinence in the elderly. AB - The successful management of constipation and fecal incontinence in the elderly requires an understanding of colorectal function, careful delineation of the patient's complaint, and in selected patients, specialized studies of colonic and anorectal function. This article reviews (1) the prevalence and nature of lower bowel dysfunction in the elderly population: (2) colonic and anorectal physiologic changes that are associated with aging; (3) the causes, consequences, and approaches to the management of constipation in the elderly; and (4) the causes of fecal incontinence in this age group and the treatment available. PMID- 2194953 TI - Biliary and pancreatic disease in the elderly. AB - Cholelithiasis and its complications, along with malignancy, account for the majority of biliary and pancreatic diseases in the elderly and increase in frequency with advancing age. The presentation is often subtle and requires a high index of suspicion on the part of the clinician. Surgical management of pancreaticobiliary disease usually is associated with an increased morbidity and mortality relative to younger patients, although in some cases surgery still remains the best treatment modality. A major advance has been the development of nonsurgical therapeutic techniques, such as endoscopic sphincterotomy and biliary endoprostheses. PMID- 2194954 TI - Nutritional requirements in the elderly. AB - Nutritional management of elderly persons can be difficult because of illness, drug-nutrient interactions, socioeconomic factors, and lack of precise information regarding nutrient requirements. Dietary intake and requirements, nutritional assessment, and guidelines for nutritional management of the elderly population are reviewed. PMID- 2194956 TI - Effects of anti-inflammatory agents on mucosal inflammation induced by infection with gram-negative bacteria. AB - Gram-negative bacterial infections of the urinary tract elicit a mucosal inflammatory response. Interleukin-6 is secreted into the urine, and polymorphonuclear leukocytes (PMNL) are recruited. In the present study we examined the effect of anti-inflammatory agents on these parameters and on bacterial clearance from the kidneys. Dexamethasone reduced interleukin-6 secretion, the PMNL response, and bacterial clearance. Diclofenac abolished the urinary interleukin-6 response but reduced the PMNL response and bacterial clearance only at the highest concentrations. Indomethacin drastically decreased bacterial clearance without the corresponding effect on interleukin-6 production or the PMNL response. The results demonstrate that the inhibition of inflammation impairs bacterial clearance from the kidneys. This is, however, not a direct function of inhibited interleukin-6 production or PMNL recruitment. PMID- 2194955 TI - Expression in Escherichia coli of the 37-kilodalton endoflagellar sheath protein of Treponema pallidum by use of the polymerase chain reaction and a T7 expression system. AB - We previously reported the complete primary structure of the 37-kilodalton endoflagellar sheath protein (FlaA) of Treponema pallidum. However, we were unable to determine the nucleotide sequence of flaA upstream of amino acid 10. The desired nucleotide sequence was obtained by use of a strategy based upon the polymerase chain reaction and was found to contain a consensus Escherichia coli promoter, a ribosomal binding site, and a 20-amino-acid signal peptide. Expression of FlaA in E. coli was achieved by cloning polymerase chain reaction derived constructs lacking the native T. pallidum promoter into a temperature inducible T7 expression system. Pulse-chase and ethanol inhibition analyses of protein processing in E. coli cells and minicells, respectively, indicated that processing of the FlaA precursor was incomplete. Native and recombinant FlaA were identical as assessed by antibody reactivity and sodium dodecyl sulfate- and two dimensional polyacrylamide gel electrophoretic mobilities. Soluble FlaA was not detected in either the cytoplasmic or the periplasmic fractions of E. coli transformants. Fractionation of E. coli cell envelopes unexpectedly revealed that FlaA precursor and FlaA were associated with both the cytoplasmic and outer membranes. This is the first report of expression in E. coli of a T. pallidum protein which could not be cloned or expressed with its native promoter. Our data also indicate that information obtained in E. coli regarding the subcellular location of cloned treponemal proteins must be cautiously extrapolated to T. pallidum. PMID- 2194957 TI - Mannan composition of the hyphal form of two relatively avirulent mutants of Candida albicans. AB - We have previously reported the characteristics of mannans isolated from the yeast forms of two relatively avirulent Candida albicans strains, designated 4918 2 and 4918-10. Investigations have been expanded to include an analysis of mannans from the hyphal form of these strains as well as from the hyphal form of the parental strain, 4918. After extraction, mannans were further purified by high-pressure liquid chromatography on a Bio-gel TSK DEAE-5-PW column. Subsequent to either mild acid hydrolysis, alkali hydrolysis, or acetylation followed by acetolysis, the resulting products were fractionated by high-pressure liquid chromatography on an Aminex HPX-42A column. The results of acid hydrolysis showed only minor quantitative differences in the products released from each strain, with mannose constituting the vast majority of product liberated. The profiles of mannooligosaccharides obtained from either alkali hydrolysis or acetolysis for strain 4918-2 showed distinct quantitative differences compared with profiles of the other two strains. Finally, a general characteristic noted is a decrease in the average chain length of mannooligosaccharides in hyphal mannans compared with the yeast counterpart. PMID- 2194958 TI - Cryptococcus neoformans, Candida albicans, and other fungi bind specifically to the glycosphingolipid lactosylceramide (Gal beta 1-4Glc beta 1-1Cer), a possible adhesion receptor for yeasts. AB - The role of glycosphingolipids as adhesion receptors for yeasts was examined. Cryptococcus neoformans, Candida albicans, and Saccharomyces cerevisiae, as well as Histoplasma capsulatum and Sporotrichum schenckii (in their yeast phases), bound specifically to lactosylceramide (Gal beta 1-4Glc beta 1-1Cer), as measured by overlaying glycosphingolipid chromatograms with 125I-labeled organisms. An unsubstituted galactosyl residue was required for binding, because the yeasts did not bind to glucosylceramide (Glc beta 1-1Cer) derived from lactosylceramide by treatment with beta-galactosidase or to other neutral or acidic glycosphingolipids tested that contained internal lactosyl residues. Interestingly, the yeasts preferentially bound to the upper band of the lactosylceramide doublet in human lung and bovine erythrocytes, suggesting that the ceramide structure also affects binding. Active metabolism of the yeasts was required for binding to lactosylceramide, as binding was maximal in buffer containing glucose and was almost completely abolished in nutrient-deficient medium. C. neoformans also bound to human glioma brain cells grown in monolayers, and this binding was inhibited by liposomes containing lactosylceramide but not by liposomes containing glucosylceramide. Lactosylceramide is a major glycosphingolipid in these cells and the only one to which the yeasts bound. As lactosylceramide is widely distributed in epithelial tissues, this glycosphingolipid may be the receptor for yeast colonization and disseminated disease in humans. PMID- 2194960 TI - Opsonic activity of cerebrospinal fluid in experimental cryptococcal meningitis. AB - The role of antibody in protection against infection with Cryptococcus neoformans is undefined. In this paper we describe the development of opsonic activity in the cerebrospinal fluid (CSF) of rabbits in response to cryptococcal meningitis. The opsonin appeared to be immunoglobulin G (IgG); the activity was heat stable, copurified with the IgG fraction during protein A separation, and could be absorbed by encapsulated cryptococci. Immunosuppression with cyclosporine could be administered to prevent or allow in vivo deposition of IgG on the polysaccharide capsule of yeast in the CSF. Both early and late cyclosporine regimens resulted in prolonged, severe meningeal infections corresponding to the complete absence of in vitro opsonic activity in the CSF. While the production of opsonic antibody is part of the successful host response against C. neoformans in the central nervous system of rabbits, the presence of specific immunoglobulin by itself is insufficient for complete protection. PMID- 2194959 TI - Production and characterization of monoclonal antibodies to cell wall antigens of Aspergillus fumigatus. AB - Two murine monoclonal antibodies (MAbs) against Aspergillus fumigatus were produced and characterized. Splenocytes from cell wall-immunized BALB/c mice were fused with SP2/0 myeloma cells. The hybridomas were screened with a cold alkali (CA) extract of mycelium containing protein, mannose, and galactose, and two MAbs of the immunoglobulin M class were purified from ascites fluid. MAbs 1 and 40 were characterized by double immunodiffusion against CA antigen, indirect enzyme immunoassay with mannans of Candida albicans serotypes A or B or Candida tropicalis, indirect immunofluorescence with C. albicans- or A. fumigatus infected tissues, indirect immunofluorescence with smears of other pathogenic fungi, Western blotting (immunoblotting) with the lectin concanavalin A or BS-1 from the seeds of Bandeirea simplicifolia, and immunoelectron microscopy. MAb 1 did not cross-react with Candida mannan and recognized a periodate-sensitive, pronase- and heat-resistant epitope in CA antigen and three mannose- and galactose-containing components (80, 62, and 49 kilodaltons) of a mycelial homogenate. Immunoelectron microscopy demonstrated binding of MAb 1 to the inner cell wall and intracellular membranes of hyphae and conidia of A. fumigatus. Circulating antigen was detected in experimental invasive aspergillosis by inhibition enzyme immunoassay with MAb 1 and CA antigen. MAb 40 was a nonprecipitating antibody cross-reactive with Candida species, and competition for an epitope located diffusely in the cell wall of A. fumigatus hyphae was demonstrated by incubating MAb 40 with mannan of C. albicans serotype A. These results suggest that MAb 1 recognizes immunodominant oligogalactoside side chains of A. fumigatus galactomannan, while MAb 40 binds to mannopyranosyl side chains common to A. fumigatus galactomannan and C. albicans mannan. PMID- 2194961 TI - Functional analysis of the sialic acid-binding adhesin SfaS of pathogenic Escherichia coli by site-specific mutagenesis. AB - The gene coding for the sialic acid-specific adhesin SfaS produced by the S fimbrial adhesin (sfa) determinant of Escherichia coli has been modified by oligonucleotide-directed, site-specific mutagenesis. Lysine 116, arginine 118, and lysine 122 were replaced by threonine, serine, and threonine, respectively. The mutagenized gene clusters were able to produce S fimbrial adhesin complexes consisting of the S-specific subunit proteins including the adhesin SfaS. The mutant clones were further characterized by hemagglutination and by enzyme-linked immunoassay tests with antifimbria- and anti-adhesin-specific monoclonal antibodies, one of which is able to block S-specific binding (Moch et al., Proc. Natl. Acad. Sci. USA 84:3462-3466, 1987). The lysine-122 mutant clone was indistinguishable from the wild-type clone in these assays. Replacement of lysine 116 and arginine 118, however, abolished hemagglutination and resulted in clones which showed a weak (lysine 116) or a negative (arginine 118) reaction with the antiadhesin-specific antibody A1. We therefore suggest that lysine 116 and arginine 118 have an influence on binding of SfaS to the sialic acid residue of the receptor molecule. Substitution of arginine 118 by serine also had a negative effect on the amount of SfaS adhesin proteins isolated from the S fimbrial adhesin complex. PMID- 2194962 TI - Activation of the plasma kallikrein-kinin system by Candida albicans proteinase. AB - An extracellular carboxyl proteinase produced by the yeast Candida albicans enhanced vascular permeability when injected into the dorsal skin of guinea pigs. The character and mechanism of the permeability-enhancing reaction were studied in vivo and in vitro. Permeability was not enhanced when the C. albicans proteinase was heat treated (100 degrees C, 5 min) or when it was treated with pepstatin, a specific carboxyl proteinase inhibitor. The permeability reaction induced by the C. albicans proteinase was not affected by pretreatment with antihistamine but was greatly augmented by simultaneous injection of a kinin potentiator, carboxypeptidase N inhibitor. However, the simultaneous injection of a kinin-degrading enzyme, carboxypeptidase B, interfered with the reaction. Furthermore, in vitro conversion of plasma prekallikrein to kallikrein by the C. albicans proteinase was observed, and the reaction was inhibited by corn trypsin inhibitor, an inhibitor of activated Hageman factor, and soybean trypsin inhibitor, a well-known inhibitor of plasma kallikrein. These results indicate that C. albicans proteinase enhances vascular permeability through activation of the plasma kallikrein-kinin system, which generates bradykinin. PMID- 2194963 TI - Characterization of the heat shock response and identification of heat shock protein antigens of Borrelia burgdorferi. AB - The heat shock response of Borrelia burgdorferi B31 cells was characterized with regard to the heat shock proteins (Hsps) produced. Five to seven Hsps were detected by sodium dodecyl sulfate-gel electrophoresis and fluorography of proteins from cells labeled with [35S]methionine after shifts from 33 degrees C to 37 or 40 degrees C or from 20 degrees C to 33, 37, or 40 degrees C. Analysis of [35S]methionine-labeled Hsps by two-dimensional electrophoresis and autoradiography revealed 12 Hsps. Western immunoblot analysis with antisera to highly conserved Escherichia coli and Mycobacterium tuberculosis Hsps revealed a single 72-kilodalton (kDa) protein band that reacted with antibodies to E. coli DnaK and with antibodies to the M. tuberculosis 71-kDa Hsp homolog of E. coli DnaK. Two proteins with apparent molecular masses of 66 and 60 kDa reacted with antibodies against the M. tuberculosis 65-kDa Hsp homolog of E. coli GroEL. Human immune sera collected from patients with Lyme disease reacted with both the 66 kDa Hsp and the 60-kDa Hsp but failed to react with the 72-kDa Hsp. These data are discussed with regard to the possibility that host recognition of highly conserved epitopes of GroEL homologs of B. burgdorferi may result in autoimmune reactions causing arthritis and other pathologies. PMID- 2194964 TI - Repertoires of antibodies to culture filtrate antigens in different mouse strains infected with Mycobacterium bovis BCG. AB - Two susceptible (Bcgs) mouse strains, BALB/c and C57BL/6, were compared by Western blot (immunoblot) analysis for their immunoglobulin G response to 14-day old BCG culture filtrate (CF) following intravenous infection with live Mycobacterium bovis BCG. The two strains demonstrated a completely different antibody repertoire. BALB/c antibodies were directed against a wide range of CF antigens between 20 and about 100 kilodaltons (kDa), with a preferential recognition of the 65-kDa heat shock protein and the 32-kDa fibronectin-binding protein. C57BL/6 sera, on the other hand, showed a much more restricted antibody pattern, almost exclusively directed against three antigens with estimated molecular sizes of 37, 38, and 40 kDa. Whereas the 37- and 38-kDa antigens were also recognized by BALB/c mice, the 40-kDa antigen was very intensely stained by C57BL/6 sera only. F1 mice had the restricted antibody pattern of C57BL/6 after one injection of BCG and had a hybrid BALB/c-C57BL/6 phenotype following a boost injection of BCG 2 months after the initial infection. Analysis of seven recombinant inbred strains derived from the BALB/c x C57BL/6 cross and of congenic mice differing in major histocompatibility complex-coding chromosome 17 fragments suggests that a gene in the K-IA region of the H-2 locus is associated with the preferential recognition of certain CF antigens. Inoculation with the same dose of killed BCG failed to elicit an antibody response to these filtrate antigens. PMID- 2194965 TI - Oral and esophageal Candida albicans infection in hyposalivatory rats. AB - The opportunistic fungus Candida albicans is a major cause of oral and esophageal infections in immuno-compromised patients, individuals on drug therapy, and the chronically ill. Because it has been observed that persons suffering from hyposalivation have an increased prevalence of oral candididiasis, we developed an animal model of infection based on hyposalivation. The objectives of our studies were to understand the mechanisms by which C. albicans causes oral disease and to begin to elucidate the role played by saliva in controlling C. albicans in the oral cavity. Our results showed that (i) oral Candida infection was established by a small challenge inoculum, (ii) mucosal lesions developed in the oral cavities and esophagi of infected rats, and (iii) transmission of oral Candida infection from an inoculated rat to uninoculated cagemates occurred rapidly. In addition, we compared the abilities of a clinical isolate and a spontaneously derived morphological mutant from that isolate to infect hyposalivatory rats and to induce disease. Infection was induced by the morphological mutant in hyposalivatory rats; however, the morphological mutant took significantly longer to transmit oral infection to uninoculated cagemates than did the parental strain. PMID- 2194966 TI - Genetic evidence that the yopA gene-encoded Yersinia outer membrane protein Yop1 mediates inhibition of the anti-invasive effect of interferon. AB - HEp-2 cell monolayers were challenged with genetic variants of Yersinia pseudotuberculosis YPIII(pIB1) and Yersinia enterocolitica W22708(pYL4). Both strains were represented by (i) variants harboring the 70-kilobase virulence plasmid, (ii) their isogenic plasmid-cured derivatives, and (iii) two transposon mutants constructed by insertional inactivation of the plasmid genes encoding outer membrane protein Yop1 and Ca2+ dependency in strains YPIII(pIB1) and W22708(pYL4). When the HEp-2 cells were pretreated with recombinant alpha interferon subtype A, all invasive variants of Y. enterocolitica and Y. pseudotuberculosis, except those variants which expressed Yop1, showed a significantly reduced ability to localize intracellularly. The anti-invasive effect of interferon was abolished when the gene was expressed or when a sterile filtered sonic extract of a Yop1-producing strain was added to the cell cultures. To obtain further evidence of a potential role of Yop1, a DNA fragment encoding Yop1 cloned into the vector pBR322 was used. After introduction of the resultant recombinant plasmid pYMS2 into the plasmid-cured variant YPIII and the Yop1 negative transposon mutant YPIII(pIB102) of Y. pseudotuberculosis, both transformants regained the ability to produce Yop1 and showed complete inhibition of the interferon effect. Moreover, the sterile sonic extract of an Escherichia coli strain, which carried pYMS2, neutralized the anti-invasive effect of interferon. The results provide direct genetic evidence that Yop1 mediates inhibition of the anti-invasive effect of interferon in HEp-2 cell cultures. The results also demonstrated that Yop1 itself reduces the ability of Yersinia spp. to localize intracellularly in HEp-2 cells. PMID- 2194967 TI - Moderate immunodeficiency does not increase susceptibility to Salmonella typhimurium aroA live vaccines in mice. AB - Salmonellae carrying appropriate mutations in genes of the aromatic biosynthesis pathway are effective as live vaccines in animals, and they are candidate typhoid vaccines for human use. They are also very effective as carriers of recombinant antigens from other pathogens to the immune system, eliciting circulatory, secretory, and cell-mediated immunity to foreign antigens. Their attenuation is believed to be due to their requirement for the metabolites p-aminobenzoic acid and 2,3-dihydroxybenzoate, which are not available in mammalian tissues. Immunosuppression (e.g., acquired immunodeficiency syndrome) is a major contraindication to the use of live vaccines. If the avirulence of Aro mutants is largely due to their auxotrophy, they should not be markedly more invasive in immunosuppressed animals. We report that wild-type Salmonella typhimurium M525 of intermediate virulence was much more invasive in sublethally irradiated BALB/c mice than in normal BALB/c mice, whereas sublethal irradiation had little if any effect on the invasiveness of an S. typhimurium aorA vaccine strain apart from a delay in its clearance from the reticuloendothelial system. xid mutant CBA/N mice carry an X-linked B-cell functional defect which results in immunoglobulin G3 agammaglobulinemia, and they are known to be more susceptible to salmonellae in late stages of the infection. We found that whereas male (CBA/N x BALB/c)F1 mice (immunodefective) were more susceptible to wild-type S. typhimurium C5 than female littermates (immunocompetent), there was no difference in the response to the S. typhimurium aroA vaccine strain. The results indicate that moderate immunosuppression does not markedly enhance susceptibility to S. typhimurium aroA live vaccines. PMID- 2194968 TI - Immunity to experimental fowl typhoid in chickens induced by a virulence plasmid cured derivative of Salmonella gallinarum. AB - Chickens were immunized by two intramuscular inoculations at 1 and 14 days of age with virulence plasmid-cured derivatives of Salmonella gallinarum and were challenged 14 days later by oral inoculation of ca. 50 50% lethal doses (LD50) of fully virulent S. gallinarum 9. Mortality in the nonimmunized and immunized groups were 36 and 3%, respectively. This difference was highly significant (P less than 0.01). A significant reduction in mortality was also produced following oral challenge with 5,000 LD50 doses. The LD50 values by intramuscular inoculation of the challenge organism into nonimmunized and immunized chickens were log10 (0.13 +/- 1.57) and (9.74 +/- 2.72), respectively. Immunization was effective whether chickens were immunized at 1 and 14 days of age or at 21 and 35 days of age. Serum agglutinins were present in immunized chickens. Immunization with plasmid-cured Salmonella pullorum gave less protection, and immunization with Escherichia coli K-12 possessing the virulence plasmid of S. gallinarum gave none. The plasmid-cured S. gallinarum was made both rough by virulent bacteriophage activity and nalidixic acid resistant (Nalr) to produce a strain designated 9VP-phi rNalr. It was compared with a Nalr mutant of the rough 9R vaccine strain designated 9 Nalr for virulence and immunogenicity. 9VP-phi rNalr was slightly less protective and less virulent than was the 9R vaccine strain. PMID- 2194970 TI - Comparative study of attachment to and invasion of epithelial cell lines by Shigella dysenteriae. AB - Henle 407 and HeLa cells were compared as hosts for Shigella dysenteriae at a low multiplicity of infection. Efficiency of attachment and invasion without centrifugation, as well as selectivity for pathogenic over nonpathogenic S. dysenteriae without Congo red, were much greater for Henle 407 cells than for HeLa cells. PMID- 2194969 TI - Dynamics of the phagocytic cell response within the lungs of parabiotic mice infected with mycobacteria with decreasing virulence for mice. AB - Alveolar macrophages constitute the first line of defense against an aerogenic mycobacterial challenge. The kinetics of the alveolar macrophage response to an infectious stimulus was studied in parabiotic (C57BL/6 x DBA/2 [B6D2]F1 hybrid mice pulse-labeled with tritiated thymidine given to one (donor) animal while the other (recipient) received an equivalent amount of "cold" thymidine. Lavage fluid collected from uninfected recipients yielded few labeled monocytes. However, after introduction of 10(5) viable Mycobacterium bovis BCG into the lung, an immediate influx of heavily labeled mononuclear cells was observed, peaking around day 3. This cellular response was compared with that induced by several members of the Mycobacterium avium complex of different virulence to mice. The strains M. avium 724 and M. intracellulare 1405, virulent to mice, induced moderate mononuclear cell responses, whereas the avirulent M. intracellulare 1411 induced a predominantly polymorphonuclear rather than mononuclear cell influx, analogous to that seen when heat-killed mycobacteria were introduced into the lung. These results suggest that the mycobacteria within the lung must remain in a metabolically active state in order to induce the maximum mononuclear cell response of the type associated with acquired antituberculous immunity. PMID- 2194971 TI - Efficacy of the combination pivampicillin/pivmecillinam compared to placebo in the treatment of convalescent carriers of nontyphi Salmonella. AB - In a randomized, double blind, placebo-controlled study 36 patients aged 16-77 years who had been carriers of nontyphi Salmonella species for 10-21 weeks were given the combination pivampicillin/pivmecillinam or placebo for four weeks in order to eradicate the carrier state. 34/36 patients who fulfilled the criteria for inclusion in the study were evaluable for efficacy, 16 in the pivampicillin/pivmecillinam group and 18 in the placebo group. Seven patients in the pivampicillin/pivmecillinam group had to terminate the treatment after 10-25 days because of adverse reactions, mainly exanthema and nausea. After therapy 8/16 patients treated with pivampicillin/pivmecillinam and 4/18 patients treated with placebo had negative stool cultures for Salmonella species during a mean follow-up time of 13 and 20 weeks, respectively. No abnormalities could be found in those patients who did not respond to therapy except for earlier cholecystectomy in two patients, both in the pivampicillin/pivmecillinam group. PMID- 2194973 TI - Aesthetic limits of light-cured composite resins in anterior teeth. AB - The aesthetic limits of light-cured composite resins in anterior teeth are determined mainly by the size and nature of the lesion and the respective preparation. Also the shortcomings of the restorative material itself are of primary importance. The oral environment and the ageing effects ultimately limit the aesthetic expectations. PMID- 2194972 TI - Therapeutic effects of cefpirome (HR 810) on experimental mixed infections with Enterococcus faecalis and Escherichia coli in mice. AB - The therapeutic effects of cefpirome (HR 810), a new cephalosporin, on mixed infections induced in mice with Enterococcus faecalis HL1147 and Escherichia coli HL34 were compared with those of ampicillin (AMP), cefuzonam (CZON), and ceftazidime (CAZ). Cefpirome was more effective in protecting mice with systemic mixed infection (median effective dose, 52 mg/kg) than the other antibiotics (all more than 320 mg/kg). With increasing doses of cefpirome, the percentages of the animals having E. faecalis and E. coli bacteremia were decreased. CZON and CAZ reduced only E. coli, and AMP failed to reduce both strains. In the mice with urinary tract mixed infection, cefpirome and CZON (40 mg/kg x 5, s.c.) significantly decreased the cfu/g kidney (p less than 0.01 vs. nontreated control), while AMP and CAZ were active only against E. faecalis (p less than 0.05) and E. coli (p less than 0.01), respectively. PMID- 2194974 TI - Classification of periodontal diseases. AB - The classification of periodontal diseases used and taught in the Department of Periodontology at The University of Sarajevo, Yugoslavia is presented and explained. The classification is the result of nearly 20 years' work. It is based on the inflammatory process and a combination of topography, morphology, pathology and aetiology of periodontal diseases. PMID- 2194975 TI - How much reduction of the dental arch is functionally acceptable for the ageing patient? AB - Dental care should be aimed at the preservation of a natural functioning dentition for life, within the available resources. In general, preference should be given to dentitions comprising complete dental arches or 14 occluding pairs of teeth. However, in many subjects--such as the elderly--this goal might be neither attainable nor necessary. In these cases, dental care should be aimed at preserving the strategic parts of the dental arch, which are the front and premolar regions (the so-called ultimate occlusal preservation target). Clinical observation as well as research findings indicate that elderly people can function at an acceptable level with a reduced dentition consisting of 10 or even fewer occluding pairs. The minimum size of a functional dental arch differs between individuals and depends on local and systemic factors. Important indicators are the age, the (periodontal) quality of the remaining dentition, the spatial relationship between the lower and upper teeth, the occlusal activity and the adaptive capacity. Dental health care systems should implement guidelines to concentrate the available resources primarily on the strategic regions of the dental arch, especially in high-risk groups. These guidelines should be based on research results. The main objective of this paper is to contribute to defining an acceptable oral status for elderly subjects. PMID- 2194976 TI - Insulin therapy of diabetes with implantable infusion pumps: clinical aspects. PMID- 2194977 TI - Changes in antepartum heart rate patterns with progressive deterioration of the fetal condition. AB - In this paper changes in antepartum fetal heart rate (FHR) patterns are described, that occur with progressive deterioration of the fetal condition. The data on the relationship between heart rate patterns and fetal blood gas and pH values are reviewed. A possible rank ordering is presented in which changes in FHR pattern, body movements and blood flow velocity wave form patterns occur with progressive deterioration of the fetal condition. It is concluded that in small for-date fetuses changes in heart rate and movement patterns are rather late signs of impairment, coinciding with fetal hypoxaemia. In general, heart rate variation falls below the norm at the same time as decelerations occur; there are, however, large inter-fetal differences. In general, abnormal Doppler velocity wave form patterns precede the occurrence of heart rate decelerations. Their impact on the timing of delivery is, however, still uncertain. The advantages of a numerical analysis of FHR patterns include identification of fetuses with low FHR variation, precision of the actual fetal condition and (at early gestation) longitudinal follow-up of fetuses with abnormal heart rate patterns. PMID- 2194978 TI - Spectral analysis of fetal heart rhythm in relation to fetal regular mouthing. AB - Fetal heart rate variation during fetal regular mouthing in behavioural state 1F was investigated applying spectral analysis. Periods with and without fetal regular mouthing movements were compared. The power spectrum of the periods with regular mouthing movements showed a peak at the frequency of the clusters of mouthing movements which was absent in the power spectrum of the corresponding periods without movements. The oscillations in the fetal heart rate associated with this peak in the power spectrum were detectable both in the heart rate tracings obtained from the abdominal electrocardiogram and those recorded by means of wide range Doppler ultrasound. PMID- 2194979 TI - Computer analysis of antepartum fetal heart rate: 1. Baseline determination. AB - A consequent and reproducible determination of baseline is an essential prerequisite for objective interpretation of fetal heart rate. A fully automated off-line method of baseline determination has been developed and tested on 50 normal antepartum fetal heart rate recordings of two hours duration. The method is constructed around two functional units, a digital filter and a trim function, which interact in an iterative process. The results were evaluated in comparison with automated baseline determination according to Dawes and coworkers. A panel of 3 experts agreed that in 14 of the 50 recordings (28%), the new developed procedure resulted in a substantially better baseline fit. In the remaining 34 recordings (72%), baseline fit from both methods was judged as equivalent. The described procedure of baseline determination provides a solid base for automated detection of accelerations and decelerations in fetal heart rate recordings. It enables the study of the relation between the fetal heart rate pattern and fetal movements. Finally, it provides an objective tool for analysis of variables within the fetal heart rate with the highest predictive value with respect to fetal outcome. PMID- 2194980 TI - Computer analysis of antepartum fetal heart rate: 2. Detection of accelerations and decelerations. AB - Based upon a previously described procedure for automated baseline determination in antepartum fetal heart rate recordings, a programme has been developed for recognition of accelerations and decelerations. Detection of these deviations from the baseline depends on criteria for amplitude and duration, with special account for signal loss. The described automated analysis provides an objective tool for description of antepartum fetal heart rate patterns. A first evaluation with respect to its capacity to discriminate between different fetal heart rate patterns in relation to fetal rest-activity patterns shows promising results. PMID- 2194981 TI - Establishment of highly metastatic variants of murine colon adenocarcinoma 26 under serum-free conditions. AB - Tumor cell variants were established in vitro by treating a metastatic variant of murine colon adenocarcinoma 26 (P-26-select) in serum-free RPMI 1640 medium for 6 to 10 weeks. Five tumor cell lines were established from independent cultures and designated PS-1 to PS-5. The PS cells showed higher growth potential in vitro under serum-free or low-serum conditions than the parental P-26-select. In comparison to P-26-select, the PS cell lines possessed enhanced lung-colonizing ability after i.v. inoculation and metastasized spontaneously to the lung following s.c. inoculation into the flank or the right fore-footpads of BALB/c mice. Metastatic nodules were also observed in the liver. Spleens and livers of the tumor-bearing mice were enlarged mainly as a result of hematopoiesis, suggesting the production of CSF-like substance(s) by the tumor cells. The PS cells secreted increased amounts of putative autocrine growth factor(s) and CSF like substance(s) in vitro. These characteristics might be related to the in vivo metastatic ability of the PS cells. PMID- 2194982 TI - Generation and characterization of monoclonal antibodies to prostate secretory protein. AB - Monoclonal antibodies (MAbs) were produced against a highly purified preparation of prostate secretory protein (PSP) isolated from normal seminal plasma. Fifteen antibodies were selected for further evaluation based on their strong reactivity and specificity for PSP. All the MAbs had a specificity for prostate epithelial cells and none reacted to any of a variety of normal tissues as determined by immunoperoxidase staining. Six of the MAbs were selected for further immunohistochemical evaluation based on their ability to recognize different antigenic determinants. Using competitive binding immunoassays, a variety of overlapping specificities were observed with at least 2 distinct epitopes identified. Although some staining variability was noted, the 6 antibodies, in general, gave the same pattern of tissue reactivity. Both the normal prostate and the benign prostate hyperplastic ductal epithelial cells stained intensely, with 78 to 100% and 50-100% of the cells staining, respectively. The number and often the staining intensity of the tumor cells decreased as the tumor became more undifferentiated. Approximately 40 to 100% and 15 to 70% of the tumor cells stained in the moderately-differentiated and well-differentiated carcinoma tissues, respectively, whereas either no staining was observed or less than 20% of the tumor cells stained in the poorly-differentiated and undifferentiated tumors. Most of the metastatic prostate tumors showed either no staining or scattered staining in a few cells (i.e., less than 20%). PMID- 2194983 TI - Pharmacological modification of multi-drug resistance (MDR) in vitro detected by a novel fluorometric microculture cytotoxicity assay. Reversal of resistance and selective cytotoxic actions of cyclosporin A and verapamil on MDR leukemia T cells. AB - A novel fluorometric microculture cytotoxicity assay (FMCA), based on measurements of fluorescein diacetate (FDA) hydrolysis and DNA staining by Hoechst 33342, was used for drug sensitivity testing and detection of resistance reversal in acute lymphoblastic leukemia (ALL) cell lines. The 72-hr assay was found to be sensitive, reproducible and linearly related to the number of viable cells within a broad range of cell concentrations. At clinically achievable drug concentrations, the calcium channel blocker Verapamil (ver) and the immunosuppressant Cyclosporin A (csA) were found to partly reverse acquired Vincristine (vcr) resistance in multi-drug resistant (MDR) T-ALL L100 cells with little or no effect on the drug-sensitive parental L0 cell line. By combining the fluorometric indices, we found that low concentrations of csA were growth inhibitory, whereas higher concentrations (greater than 10 micrograms/ml) were progressively cytotoxic for drug-sensitive L0 cells. In MDR L100 cells, on the other hand, csA produced significant cell kill even at low drug concentrations. Ver had no effects on sensitive L0 cells but showed considerable cytotoxic action towards MDR L100 cells. There was no apparent relationship between drug reversal of vcr resistance and the cytotoxic actions of the drug per se since the calcium channel blocker diltiazem (dil) significantly potentiated the actions of vcr on MDR L100 cells without being more toxic to these cells (compared to vcr-sensitive L0 cells). PMID- 2194984 TI - Endogenous opioid peptides and cardiac arrhythmias. PMID- 2194985 TI - Endomyocardial fibrosis--the possible connexion with myocardial levels of magnesium and cerium. PMID- 2194986 TI - Artificial cardiac pacemakers. AB - Artificial pacemakers are electronic devices used primarily to control cardiac rate in patients in whom the intrinsic heart rate is inadequate for a normal life style. These devices automatically and rhythmically provide electrical impulses to stimulate the heart. Electrical stimulation of various organs of the human body was already in practice more than two centuries ago. These applications, however, were in experimental stages until recently when electrical stimulation of the heart has emerged as a new therapy. In view of the astonishing progress made in the field of pacemaker technology and the current indications for the specific types of pacing systems, it behooves physicians caring for patients with heart disease to become familiar with the use of cardiac pacemakers and the not infrequent problems associated with their use. The primary purpose of this review is to present fundamental knowledge in the electrical stimulation of the heart and the various pacing systems available. PMID- 2194987 TI - Serum concentrations of phenylpropanolamine and associated effects on blood pressure in normotensive subjects: a pilot-study. AB - This study was undertaken to investigate the effects of racemic phenylpropanolamine (PPA) on blood pressure (BP) in normotensive human subjects following the administration of three different dosages of PPA (25 mg, 50 mg and 100 mg) as single doses and to determine whether any relationship existed between the serum concentrations of PPA and its possible effects on BP. Blood was sampled and BP measured at specified times. Phenylpropanolamine was determined by HPLC with UV detection. No significant changes in BP occurred following the 25 mg dose (5 +/- 7/6 +/- 6 mm Hg), whereas statistically significant changes were found after the two higher doses of 50 mg (26 +/- 16/12 +/- 13 mm Hg) and 100 mg (30 +/ 13/15 +/- 8 mm Hg). Increases in systolic pressure following the 50 mg and 100 mg doses appeared to show a better correlation with peak serum concentrations of PPA than did diastolic effects. Although serum concentrations of PPA increased linearly with increasing dose, no clear-cut correlation could be found between serum concentrations and BP effects. The pressor effects, however, became more noticeable following the 50 mg dose and were markedly increased following the 100 mg dose. Side-effects which were reported were relatively minor even at the higher doses. PMID- 2194988 TI - Immunohistochemical localization of cathepsin D in ocular tissues. AB - Cathepsin D has been believed to play an important role in the catabolism of protein in various tissues. In retinal pigment epithelium, cathepsin D degrades rod outer segments and rhodopsin into glycopeptides. To our knowledge, no reports have described the immunohistochemical localization of cathepsin D in whole ocular tissues. We investigated the reaction of bovine, rat, and human eyes with a polyclonal antibody to cathepsin D from bovine spleen. Cathepsin D immunoreactivity was observed in the cytoplasm of the following cells: epithelium and endothelium of the cornea; keratocytes; pigmented and nonpigmented epithelium of the ciliary body; epithelium and cortex of the lens; epithelium and sphincter and dilator muscles of the iris; Muller cells; ganglion cells and pigment epithelium of the retina; and endothelium of various vessels. Positively stained ocular tissues were believed to have a high activity of protein catabolism. Since cathepsin D was closely associated with phagosomes in retinal pigment epithelium, we concluded that cathepsin D probably contributes to the physiologic degradation of rod outer segments. PMID- 2194989 TI - Class II alloantigen induced on corneal endothelium. Role in corneal allograft rejection. AB - The expression of Class II major histocompatibility complex (MHC) antigens on corneal cells can be increased in vitro by (gamma-interferon) and in vivo in inflammatory reactions. The expression of Class II MHC by corneal endothelium of New Zealand White (NZW) rabbits during the rejection of corneal allografts was demonstrated by immunoperoxidase staining. Class II MHC expression by corneal endothelial cells may facilitate rejection of corneal allografts. PMID- 2194990 TI - Urinary tract infection in general practice: direct antibiotic sensitivity testing as a potential diagnostic method. AB - Direct Antibiotic Sensitivity Testing (DST) is a rapid means of diagnosing urinary tract infection (UTI) and obtaining antibiotic sensitivity patterns of the infecting organisms. In this study 227 urine samples from general practice were analysed using this technique with those obtained using the standard laboratory method. DST was shown to be 94.6% sensitive, and 80.7% specific. Escherichia coli was the commonest infecting organism. Augmentin was the most effective antibiotic tested, all organisms tested in vitro, being susceptible. Direct Sensitivity Testing is rapid, inexpensive, easy to perform, highly sensitive and specific. It should be considered by general practitioners as an alternative to the problems and delays involved in sending urine samples to the laboratory and in awaiting the results. PMID- 2194991 TI - The Jew in literature: the hated self. AB - This paper discusses the special psychological and sociological qualities of the Jew in the literature of novels, plays and short stories. From Shakespeare to Hemingway, the Jew has been assigned a special place in the psyche of the authors here described, reflecting the ongoing cultural bias as it became internalized in the selves of the authors quoted. The Jew of Shakespeare's "Shylock" reflects the 16th century bias of Shakespeare and is at a distance--although with interesting similarities--to the Jew of Hemingway. Two psychological facets of anti-Semitism in literature are primarily discussed: the group-self perception of the Jew as stereotype persona, identified over time with specific peculiarities, and the psychological perceptions (in the quoted literature) to the internalized group percept. PMID- 2194992 TI - Steady-state plasma levels during antidepressant therapy with amitriptyline and amitriptylinoxide. AB - Plasma levels of amitriptyline, amitrypylinoxide, and their metabolites were analyzed in a controlled clinical trial with two groups of depressed patients. After administration of both drugs, demethylated and hydroxylated derivatives proved to be the main metabolites, and to a great extent amitriptylinoxide was reduced to amitriptyline. Continuous oral application of 150 mg/os per day of each drug resulted in therapeutically effective concentrations in both groups; however, concentrations were two to three times higher in the group receiving amitriptyline, rather than amitriptylinoxide. Based on the steady-state plasma levels, the total clearance of amitriptyline was calculated with a magnitude of 7 ml/min per kg. A first-order kinetic model was proposed to estimate the steady state concentrations of consecutive metabolites, employing available kinetic data. Computed levels of nortriptyline after application of amitriptyline and amitriptylinoxide were 61.1 and 20.3 ng/ml, respectively, compared to nortriptyline levels determined with HPLC, which were 70.1 and 26.5 ng/ml, respectively. The model is discussed in relation to its practical use during monitoring of drug therapy with tricylics. PMID- 2194993 TI - The right to assisted suicide: protection of autonomy or an open door to social killing? PMID- 2194994 TI - Admissibility and weighing evidence of intent in right to die cases. PMID- 2194995 TI - Heterozygosity and gene flow in populations of Calomys laucha (Rodentia, Cricetidae). AB - Enzyme polymorphism was studied by means of starch gel electrophoresis on five population samples of Calomys laucha collected in different sites and seasons. C. laucha, a cricetid rodent inhabiting preferentially cultivated fields in the central-eastern plains of Argentina, is a reservoir-host of Junin virus, agent of Argentine hemorrhagic fever. Results show high levels of genic variability in all the samples (P from 62.50 to 77.27; H from 0.118 to 0.163) and low genetic distance among populations (D from 0.0024 to 0.0167). Estimations of gene flow (mean Nm = 10.78) indicate a high migration capability of the species and the possibility of further dispersal of Junin virus. PMID- 2194997 TI - Cholelithiasis and teenage mothers. AB - Between 1980 and 1988, 23 female adolescents were hospitalized at the Bronx Lebanon Hospital Center for symptomatic cholelithiasis. The known risk factors for gallstone formation in adolescents were considered. In ten of the patients (43%), none of the risk factors was present. All ten patients, however, had in common a recent history of pregnancy. This finding is consistent with the current literature on the possible mechanism of gallstone formation during pregnancy. PMID- 2194998 TI - Fellowships in Adolescent Medicine--1990. PMID- 2194999 TI - Coverage of sixty core veterinary medical journals by ten indexing and abstracting tools. AB - Ten indexing and abstracting reference sources were examined for their coverage of 60 core veterinary medical journals. The costs of the indexes also were compared. Coverage of the 60 core veterinary journals ranged from 8 of 60 journals by Current Contents--Life Sciences to 57 of 60 by Index Veterinarius. Based on yearly costs, format, and coverage of the 60 core veterinary journals, Small Animal Practice and the 2 editions of Veterinary Reference Service were determined to be the most useful for private practitioners. The Index Veterinarius gives the most complete coverage of the core veterinary journals for veterinary research workers who have access to a library. PMID- 2194996 TI - Cytochemical markers of ischaemia in the heart and brain. PMID- 2195000 TI - Seroepidemiologic survey of antibodies to Ehrlichia equi in horses of northern California. AB - The prevalence of antibodies to Ehrlichia equi in horses from the foothill regions of northern California and from the Sacramento valley (non-foothill area) was determined, using an indirect fluorescent antibody test. Horses from foothill regions had a higher prevalence of seropositivity (10.4%) and higher titer (1:10 to 1:80) than did those from non-foothill regions (3.1%; titer less than or equal to 1:10). Fifty percent of healthy horses on a foothill farm enzootic for E equi had titer to E equi, suggesting that infection with E equi can be subclinical. Six veterinarians surveyed from northern California diagnosed clinical E equi infection in 38 horses during 1985-1986 based on clinical signs of infection and observation of E equi inclusion bodies in neutrophils on blood smears. PMID- 2195001 TI - Serodiagnosis of equine monocytic ehrlichiosis in selected groups of horses in Minnesota. AB - Antibody titer to Ehrlichia risticii was determined, in 2,549 equine serum samples, using an indirect fluorescent antibody assay. During 1986, samples were obtained from the Minnesota State-Federal Equine Infectious Anemia Diagnostic Laboratory, the Minnesota Racing Laboratory, from horses admitted to the University of Minnesota Veterinary Teaching Hospital, and as a result of field investigations of horses with acute diarrhea. Results of the study revealed antibody prevalence of 33, 24, 47, and 25% for the respective groups. There was no statistical association between seropositive status and age, sex, breed, or clinical problem of horses referred to the teaching hospital. There was an increase in the total percentage of seropositive samples over the duration of the sample collection period, suggesting a seasonal exposure pattern, and E risticii was associated with clinical and subclinical infections in horses of Minnesota. PMID- 2195002 TI - African horse sickness: a continuing menace. PMID- 2195003 TI - Competencies for directors of allied health programs in academia. AB - In this three-round Delphi study, a panel of allied health educators and administrators in academia validated 114 competency statements for directors of academic allied health programs. The statements were grouped into six administrator role categories and rated on a five-position scale, ranging from essential to not important. Statements were ranked according to their mean and median. High importance and consensus (means = greater than 4.00, SD = 0.75) were reached on 42 statements. Results showed that program directors must be competent fiscal officers, teachers, and faculty leaders. As resource developers, they should be competent managers of people, and they should be competent evaluators of their programs, faculty, and staff. Program directors should demonstrate competent organizational and interpersonal skills and should be receptive to both internal and external constituencies. This study was a first step in determining generic competencies appropriate for hiring, developing, and promoting directors of academic allied health programs. PMID- 2195005 TI - [Radiotherapy and ovarian carcinoma. Experience in 139 patients]. AB - Between 1969 and the end of 1984, 104 patients with stage I to III ovarian carcinoma were referred for treatment. All patients had surgery before referral. There were 42 stage I, 32 stage II and 30 stage III patients. In one third of the patients the previous surgery was incomplete. Another 35 patients with advanced (stage IV) ovarian carcinoma or with an abdomino-pelvic recurrence after surgery were referred for palliative treatment. Distribution of the patients according to age, stage and histologic type was not different from the series reported in the literature. Radiation therapy was given over the pelvis up to 45 Gy midline dose. A lumbo-aortic field, 25 Gy up to the diaphragm, was added for stage III patients. Five year survival after complete surgery was respectively 80.5%, 65.5% and 33.3% for stage I, II and III. After incomplete surgery the data dropped to 70%, 33% and 6.6%. Overall five year survival is nevertheless 57.6%. These results are compared to similar published series (surgery and radiotherapy). The outcome is very similar. Adjuvant radiation therapy in adequate dose over the pelvis is worthwhile for ovarian carcinoma stage I-II, and with lumbo-aortic irradiation for stage III, providing surgery was aggressive. PMID- 2195004 TI - Effect of fructose consumption during lactation on sow and litter performance and sow plasma constituents. AB - The effects of dietary consumption of high-fructose corn syrup (HFCS) and dextrose during a 28-d lactation on sow and litter performance and sow plasma constituents were examined in 45 multiparous and 36 primiparous crossbred sows. Isocaloric and isonitrogenous corn-soybean meal diets were formulated to contain either 20% fructose or 20% glucose. Diets were fed on a metabolic BW basis from d 0 to d 28 of lactation. Litter and pig weights on d 28 were not affected (P greater than .05) by treatment. Litter size was greater (P less than .10) at weaning for primiparous sows fed HFCS, but multiparous sows weaned heavier (P less than .05) pigs. Sow weight change during lactation was not influenced by diet, but primiparous sows lost more (P less than .05) weight during lactation and had longer intervals to estrus than multiparous sows did. Milk yields on d 17 and 21 of lactation were not different (P greater than .05) for sows fed HFCS vs dextrose, but sows fed HFCS tended to have greater (P = .05) percentage of milk fat. Preprandial concentrations of fructose in plasma were low in sows fed HFCS and nondetectable in those fed dextrose but were elevated (P less than .05) after consumption of HFCS. Conversely, similar (P greater than .05) concentrations of glucose in plasma preprandially were followed by greater (P less than .05) postprandial glucose concentrations in sows fed dextrose. Although postprandial concentrations of insulin were not affected (P greater than .05) by diet, sows fed dextrose had greater (P less than .05) preprandial insulin concentrations in plasma. Concentrations of nonesterified fatty acids and growth hormone in plasma and response to a glucose challenge were not affected (P greater than .05) by feeding HFCS. However, concentrations of insulin in plasma following glucose infusion were less (P less than .05) during the glucose challenge period on d 25 than on d 13 of lactation. PMID- 2195006 TI - Clomipramine and obsessive compulsive disorder: a placebo-controlled double-blind study of 32 patients. AB - Thirty-two nondepressed patients with obsessive compulsive disorder were randomly assigned to treatment with clomipramine (N = 16) or placebo (N = 16) in a 10-week double-blind study. Of the 15 patients who received at least 3 weeks of clomipramine treatment, 11 (73%) improved, 5 (33%) improved by more than 50%, and none worsened. Only 2 (12.5%) of the 16 placebo-treated patients improved, 1 (6%) by more than 50%; two (13%) worsened. Clomipramine treatment was associated with statistically significant improvement on several measures of obsessive compulsive symptoms. Side effects were more frequent and severe with clomipramine than with placebo. Although most patients tolerated clomipramine well, 3 discontinued treatment because of side effects. PMID- 2195007 TI - Buspirone therapy for elderly patients with anxiety or depressive neurosis. PMID- 2195008 TI - Depression and the cancer patient. AB - The prevalence of depression in cancer patients and the types of depressive syndromes which are commonly seen are now well known. At least 25% of hospitalized cancer patients are likely to meet criteria for major depression or adjustment disorder with depressed mood. Patients at highest risk for depression are those with a history of affective disorder or alcoholism, advanced stages of cancer, poorly controlled pain, and treatment with medications or concurrent illnesses that produce depressive symptoms. The clinical evaluation of the depressed cancer patient includes careful assessment of symptoms, mental status, physical status, and cancer treatment effects. Treatment includes short-term supportive psychotherapy, antidepressant medication, and, infrequently, electroconvulsive therapy. In this article the authors review the clinical picture of depression including concern about suicidal risk and discuss pharmacologic treatment modalities. PMID- 2195009 TI - Depression in the patient with Parkinson's disease. AB - Depression is the most commonly encountered mental change in patients with Parkinson's disease. However, its cause is controversial and little is known about its natural history. Some view depression as reactive to the physical disability inherent to Parkinson's disease; however, others view the depressive disorder as the direct result of underlying biochemical changes caused by the disease process. Abnormalities within the serotonin metabolic pathway have been observed in depressed patients with Parkinson's disease and may help to explain why this form of depressive disorder is so common and persistent. Other forms of depression share this biochemical alteration. Attempts to alleviate depression with serotonin agonists have proven successful. Current research efforts are exploring biological aspects of depression in Parkinson's disease and the epidemiology of this disorder as a model of depression in the elderly, medically ill patient. PMID- 2195011 TI - Bereavement and depression. AB - Bereavement is the reaction to the loss of a loved one by death and usually occurs in three stages: numbness, depression, and recovery. The length of time it takes for bereavement to resolve varies from person to person. During the depression stage, the bereaved person may experience all the symptoms of the typical depressed patient, with the exception of retardation. However, a depressed patient has more symptoms than a bereaved person and reports feeling changed, not his or her usual self, whereas the bereaved person expects to have such symptoms. The essence of the morbidity of bereavement is the increased use of alcohol, tranquilizers, hypnotics, cigarettes, and other substances during this stressful time. Increased mortality occurs in men aged 75 years or younger in the first year of bereavement, but mortality does not increase in women or parents during that first year. Pathologic grief, defined as a continued depressive symptom, occurs in about 15% of bereaved persons when they are initially widowed. Treatment for the bereaved person should be that which is given to any depressed patient. PMID- 2195010 TI - Depression and cerebrovascular disease. AB - Depressive disorder is a common complication of stroke. Although somatic symptoms of stroke may be mistaken for depression, DSM-III criteria for major depression are appropriate for use in this clinical setting. The etiology of poststroke depression can be viewed from a number of perspectives. Evidence from examining lesion characteristics and depression suggests that a disease model is suitable for some cases of poststroke depression. Alternatively, adequacy of social support and gender differences influence the occurrence of poststroke depression. Poststroke depression can be effectively treated with tricyclic antidepressants, and the use of these agents may also enhance physical and cognitive recovery. PMID- 2195012 TI - Perspectives on the relationship between cardiovascular disease and affective disorder. AB - The relationship of major depression and cardiovascular disease has been the subject of much study. In this paper, the authors review the literature concerning the clinical importance of this relationship in four areas including the diagnosis and treatment of major depression in the setting of cardiovascular disease, the effect of concurrent major depression on the prognosis of cardiovascular disease, and the higher-than-expected rate of cardiovascular death in depressed patients. In addition, they present preliminary data which may suggest a mechanism to explain, in part, this increased rate of cardiovascular death in depression. PMID- 2195013 TI - Pharmacologic treatment of major depression for elderly patients in residential care settings. AB - A significant drug-placebo difference was found in a double-blind, placebo controlled study of nortriptyline for treatment of major depression among frail elderly patients living in an institutional setting. This finding confirms the validity of the DSM-III-R diagnosis of major depression and establishes the need for specific psychiatric services for the chronically ill elderly living in nursing homes and congregate housing facilities. The incidence of adverse events requiring early termination of treatment was 34%, demonstrating the vulnerability of these patients and their need for careful monitoring during treatment. High levels of self-care disability and low levels of serum albumin were both associated with decreased therapeutic responses, demonstrating the need for further research on psychopathology in these settings. PMID- 2195014 TI - Guidelines for diagnosis and treatment of depression in patients with medical illness. AB - Many medically ill people report depressed mood. Differentiating a true depressive syndrome from the expectable mood change due to the presence of the medical illness is problematic. The author describes criteria potentially useful in making this diagnostic differentiation and reviews predictors of treatment response in primary depression, with the implication that use of these criteria is clinically appropriate until more data on secondary depression are available. It is often necessary to formulate treatment for medically ill depressed patients on the basis of empirical observations, that is, to use a treatment trial for diagnostic as well as therapeutic purposes. In such treatment circumstances, it is imperative to use unambiguous criteria to define a therapeutic response and to stop or change treatment if these criteria are not met. PMID- 2195015 TI - Gerald P. Hodge: national treasure. AB - Gerald P. Hodge, an artist with wide-ranging interests, has been influential in shaping the medical illustration profession. His life story is presented here, with emphasis on his early years, his professional beginnings, the medical illustration program he built, his areas of research, and his creative techniques. Hodge is a Renaissance Man--a "national treasure"--and the recipient of the 1988 AMI Lifetime Achievement Award. PMID- 2195016 TI - Characterization of monoclonal antibodies to human salivary (glyco) proteins. Cellular localization of mucin, cystatin-like 14 kD protein and 20 kD glycoprotein in the human submandibular gland. AB - Using the hybridoma technique, monoclonal antibodies (Mabs) have been produced against three different types of human salivary proteins: high molecular weight mucin, a 20 kD glycoprotein and a 14 kD protein, identified as a member of the cystatin family. The Mabs appeared to be highly specific to their antigen in Elisa and immunoblotting tests. The Mabs were of the IgG-1 (against 20 kD glycoprotein) and IgM (against 14 kD protein and mucin) type. For the 14 kD protein and the 20 kD glycoprotein it was demonstrated that they are present mainly in submandibular-sublingual saliva. None of the antigens studied could be localized distinctly in the human parotid gland. In the submandibular gland, the three proteins have a different pattern of localization. The mucins have been detected particularly in the apical part of the mucous acinar cells, the 20 kD glycoprotein mainly in the serous acinar cells and the 14 kD protein in both serous acinar cells and striated duct cells. PMID- 2195017 TI - Characterization of a mouse monoclonal antibody to vimentin by indirect immunofluorescence microscopy and immunoblotting. AB - A murine IgM monoclonal antibody, termed MC15A13G was produced after immunization of Balb/c mouse with Swiss mouse dental papillae. This antibody, characterized by immunoblotting analysis and indirect immunofluorescence microscopy, recognized a 57 Kda protein identified as vimentin in different cell types with no cross reaction with other cytoskeletal proteins. PMID- 2195018 TI - Preliminary crystallographic analysis of the plant pathogenic factor, pectate lyase C from Erwinia chrysanthemi. AB - Pectate lyases are saccharide-binding enzymes that degrade plant cell walls. One pectate lyase from Erwinia chrysanthemi (EC16), termed pectate lyase C, has been crystallized from ammonium sulfate. The preliminary x-ray diffraction analysis indicates that the crystals belong to the orthorhombic space group P2(1)2(1)2(1), with unit cell dimensions, a = 73.4 A, b = 80.3 A, and c = 95.1 A. The crystals diffract to a resolution of 2.2 A and have one molecule/asymmetric unit. PMID- 2195019 TI - Nucleotide sequence and genetic characterization reveal six essential genes for the LIV-I and LS transport systems of Escherichia coli. AB - The nucleotide sequence of the genes encoding the high affinity, branched-chain amino acid transport systems LIV-I and LS has been determined. Seven genes are present on a 7568-base pair DNA fragment, six of which participate directly in branched-chain amino acid transport. Two periplasmic amino acid-binding proteins are encoded by the livJ (LIV-BP) and livK (LS-BP) genes. These two proteins confer specificity on the LIV-I and LS transport systems. livK is the first gene in a polycistronic message that includes four genes encoding membrane components, livHMGF. The protein products of the livHMGF genes are shared by the two systems. An analysis of the livH and livM DNA sequences suggests that they encode hydrophobic proteins capable of spanning the membrane several times. The LivG and LivF proteins are less hydrophobic, but are also tightly associated with the membrane. Both LivG and LivF contain the consensus sequence for adenine nucleotide binding observed in many other transport proteins. A deletion strain that does not express any of the liv genes was constructed. This strain was used to show that each of the membrane component genes is required for high affinity leucine transport, including two genes, livM and livF, for which no previous genetic evidence had been obtained. PMID- 2195020 TI - Overexpression, purification, and characterization of recombinant T4 gene 32 protein22-301 (g32P-B). AB - Gene 32 protein (g32P), the replication accessory protein from bacteriophage T4, is a zinc metalloprotein which binds with high cooperativity to single-stranded (ss) nucleic acids. The basic N-terminal 21 amino acids (termed the "B" domain) is required for highly cooperative (omega approximately 500) binding of g32P monomers to ss nucleic acids. As part of our studies to systematically evaluate the structural features of the B domain important for cooperative binding, a homogeneous source of g32P which binds noncooperatively to nucleic acids (omega = 1) and is devoid of contamination by native g32P is needed. Herein, we describe large-scale overexpression and purification of recombinant g32P lacking the tryptic N-terminal B domain (residues 1-21), designated g32P-B, as well as its physiochemical and nucleic acid binding properties. G32P-B is readily purified from the soluble fraction of Escherichia coli BL21 (DE3) transformed with the plasmid pT7g32-B.wt which contains the g32P-B coding sequences under inducible transcriptional control of T7 RNA polymerase. Anion exchange, ssDNA-cellulose and phenyl-Sepharose chromatographies give rise to highly homogeneous g32P-B, free of contaminating nucleic acid. Recombinant g32P-B has the expected N-terminal primary structure and contains stoichiometric Zn(II). It also has the expected globular structure as shown by 1H NMR spectroscopy, hydrodynamic measurements, and the ability to selectively remove the carboxyl-terminal "A" domain to form the trypsin-resistant g32P-(A + B) DNA-binding core fragment. Quantitative ss nucleic acid binding experiments of g32P-B to poly(dT) (0.05 M NaCl, pH 8.1, 20 degrees C) show that all equilibrium binding isotherms can be fit with omega = 1 and Kobs = 5.2 (+/- 1.6) x 10(5) M-1, with a moderate electrostatic component to the binding free energy, delta log Kobs/delta log[NaCl] = -3.0 +/- 0.2. Under identical solution conditions, g32P-(A + B) derived from g32P-B binds to poly(dT) noncooperatively as expected, but with an approximately 80-fold higher apparent affinity, Kobs = 4.0 (+/- 2.0) x 10(7) M-1, and detectable enhanced salt sensitivity, delta log Kobs/delta log[NaCl] = -3.9 +/- 0.3. As the salt concentration is raised, the relative difference in Kobs between the g32P-(A + B) and g32P-B is gradually reduced such that extrapolation of the log-log plots to 1 M Na+ standard state gives similar Kobs within experimental error. Qualitatively similar observations are also found upon binding to the ribohomopolymer, poly(U).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2195021 TI - 19F nuclear magnetic resonance studies of 6-fluorotryptophan-substituted rat cellular retinol binding protein II produced in Escherichia coli. An analysis of four tryptophan substitution mutants and their interactions with all-trans retinol. AB - Rat cellular retinol binding protein (CRBP II) is a 134-amino acid intracellular protein synthesized in the polarized absorptive cells of the intestine. We have previously used 19F nuclear magnetic resonance (NMR) spectroscopy to survey the structural effects of ligand binding on the apoprotein. For these studies, all 4 Trp residues of rat CRBP II were efficiently labeled with 6-fluorotryptophan (6-F Trp) by inducing its expression in a tryptophan auxotroph of Escherichia coli. Resonances corresponding to 2 of its Trp residues underwent large downfield shifts upon binding of all-trans-retinol and retinal, while resonances corresponding to the other 2 Trp residues underwent only minor perturbations in chemical shifts. To identify which Trp residues undergo changes in their environment upon ligand binding, we have constructed four CRBP II mutants where Trp9, Trp89, Trp107, or Trp110 have been replaced by another hydrophobic amino acid. By comparing the 19F NMR spectrum of each 6-F-Trp-labeled mutant with that of wild type 6-F-Trp CRBP II, we demonstrate that the 19F resonance corresponding to Trp107 undergoes the largest change in chemical shift upon ligand binding (2.0 ppm downfield). This is consistent with the position of this residue predicted from molecular modeling studies. The 19F resonance corresponding to Trp9 also undergoes a downfield change in chemical shift of 0.5 ppm associated with retinol binding even though it is predicted to be removed from the ligand binding site. By contrast, the resonances assigned to Trp89 and Trp110 undergo only minor perturbations in chemical shifts. These results have allowed us to identify residue-specific probes for evaluating the interactions of all-trans-retinol (and other retinoids) with this intracellular binding protein. PMID- 2195022 TI - Model peptides reveal specificity of N alpha-acetyltransferase from Saccharomyces cerevisiae. AB - N alpha-Acetylation is a major co-translational modification occurring at the alpha-NH2 group of eukaryotic cytosolic proteins. In order to understand better the specificity of N alpha-acetyltransferase, we used the purified enzyme from yeast (Lee, F.-J. S., Lin, L.-W., and Smith J. A. (1988) J. Biol. Chem. 263, 14948-14955) and synthetic peptides mimicking the NH2 terminus of yeast and human proteins. Alcohol dehydrogenase I-(1-24) and 8 of the 19 synthetic analogues with substitutions at the NH2-terminal residue were N alpha-acetylated with varying efficiency. Penultimate amino acid substitutions, except for proline, had little influence on N alpha-acetylation. Substitution of sequences from N alpha acetylated proteins into the yeast sequences which cannot be N alpha-acetylated demonstrated that not only the first 3 NH2-terminal residues but also more carboxyl-terminal residues were important for determining the specificity of N alpha-acetyltransferase. Two other peptides mimicking yeast mitochondrial cytochrome c oxidase (subunit VI) and ATPase inhibitor, which are naturally non acetylated, were efficiently acetylated. In addition, recombinant human alcohol dehydrogenase I and basic fibroblast growth factor, which are naturally N alpha acetylated, were not acetylated post-translationally. PMID- 2195023 TI - Quantitative detection of messenger RNA by solution hybridization and enzyme immunoassay. AB - A novel nucleic acid detection technique is described for the quantitative measurement of eukaryotic mRNA in biological samples. The procedure involves two steps: a hybridization reaction in solution with a biotinylated cDNA probe, and a conventional enzyme immunoassay that uses a monoclonal antibody for DNA.RNA hybrids to detect the specific mRNA.cDNA complexes. The method has comparable sensitivity to 32P-based methods and yields results that are quantitative and highly reproducible. Furthermore, the test can be performed using unfractionated cytoplasm without the need for extraction with organic solvents. This technique provides a rapid and quantitative method for studying changes in cellular mRNA levels, and it is suitable for testing large numbers of samples. PMID- 2195024 TI - Evidence that extracellular export of the endoglucanase encoded by egl of Pseudomonas solanacearum occurs by a two-step process involving a lipoprotein intermediate. AB - Pseudomonas solanacearum is an important phytopathogen that produces a variety of extracellular enzymes. Previous reports suggested that one of these, a 43-kDa beta-1,4-endoglucanase (EGL), is initially synthesized with a 45-residue leader sequence that is removed during export. Experiments with globomycin presented here also suggest that the primary precursor of EGL (ppEGL) has a 45-residue leader sequence but that only the first 19 residues of the leader sequence are removed by signal peptidase II during initial export across the inner membrane. Further analysis suggested that the resultant 46-kDa intermediate precursor (pEGL) is a transient fatty acylated lipoprotein and is located on the periplasmic side of the inner membrane of P. solanacearum. Although Escherichia coli could synthesize ppEGL, modify it with palmitate, and remove the first 19 residues of the leader sequence during export across the inner membrane, only P. solanacearum could export pEGL across the outer membrane and remove the remaining 26 residues of the leader sequence producing the mature, extracellular EGL. The second step of the export process requires export machinery not present in E. coli. To our knowledge this represents the first example of a leader sequence with two distinct parts, one removed during export across the inner membrane and the other removed during export across the outer membrane. PMID- 2195025 TI - Regulation of yeast LEU2. Total deletion of regulatory gene LEU3 unmasks GCN4 dependent basal level expression of LEU2. AB - We have constructed a total deletion of the regulatory gene LEU3. Comparing the deletion mutant with a leu3 spontaneous mutant, we find that both types of mutants have lost the ability to regulate a LEU2'-lacZ translational fusion by the LEU3-alpha-isopropylmalate-dependent mechanism, which we confirm to be the major regulatory mechanism for LEU2. Surprisingly, cells containing the total leu3 deletion are more leaky (i.e. grow better in the absence of extraneous leucine) than cells containing a spontaneous leu3 mutation. Accompanying the growth rate difference is a difference in the expression of the LEU2-lacZ fusion: the specific activity of beta-galactosidase amounts to about 8% of a wild type control in a leu3 total deletion mutant, but drops to about 2% in a leu3 spontaneous mutant. The spontaneous mutant differs from the total deletion mutant in that it produces an inactive protein which is still able to bind to the LEU2 upstream activating sequence. We conclude that a basal level control of LEU2 becomes manifest in the absence of LEU3 and is interfered with when LEU3 protein binds to the LEU2 promoter. This conclusion is supported by the finding that a mutant which contains an intact LEU3 gene but is unable to generate alpha isopropylmalate also interferes with basal level expression of LEU2. Basal level expression depends upon the GCN4 protein, even though LEU2 is not subject to derepression by the general amino acid control system. Changes in the steady state concentration of LEU2 mRNA show the same trend as changes in the specific activity of the LEU2-lacZ fusion protein, suggesting that regulation of LEU2 expression at both the basal and nonbasal levels is largely transcriptional. The role of alpha-isopropylmalate in the regulation of LEU2 expression appears to be that of a co-activator. Employing mobility shift assays, we show that specific interaction between the LEU3 protein and a 30-base pair DNA fragment carrying the upstream activating sequence of LEU2 takes place irrespective of the presence or absence of alpha-isopropylmalate. PMID- 2195026 TI - Full-length sequence of the cDNA for human erythroid beta-spectrin. AB - Spectrin is the major molecular consituent of the red cell membrane skeleton. We have isolated overlapping human erythroid beta-spectrin cDNA clones and determined 6773 base pairs of contiguous nucleotide sequence. This includes the entire coding sequence of beta-spectrin. The sequence translates into a 2137 amino acid, 246-kDa peptide. beta-Spectrin is found to consist of three distinct domains. Domain I, at the N terminus, is a 272-amino acid region lacking resemblance to the spectrin repetitive motif. Sequences in this region exhibit striking sequence homology, at both nucleotide and amino acid levels, to the N terminal "actin-binding" domains of alpha-actinin and dystrophin. Between residues 51 and 270 there is 55% amino acid identity to human dystrophin, with only four single amino acid gaps in alignment. Domain II consists of 17 spectrin repeats. Several sequence variations are observed in typical repeat structure. Homology to alpha-actinin extends beyond domain I into the N-terminal portion of domain II. Domain III, 52 amino acid residues at the C terminus, does not adhere to the spectrin repeat motif. Combining knowledge of spectrin primary structure with previously reported functional studies, it is possible to make several inferences regarding structure/function relationships within the beta-spectrin molecule. PMID- 2195027 TI - Structure/function analysis of interleukin-2-toxin (DAB486-IL-2). Fragment B sequences required for the delivery of fragment A to the cytosol of target cells. AB - We have used cassette and deletion mutagenesis to analyze the structural features of fragment B-related sequences in the fusion toxin DAB486-IL-2 (where IL-2 represents interleukin-2) that are necessary for the efficient delivery of fragment A to the cytosol of target cells. We demonstrate that whereas an intact disulfide bond between Cys461 and Cys471 may be required for the cytotoxic action of native diphtheria toxin, this bond is not required for the cytotoxic action of DAB486-IL-2. The in-frame deletion of the 97 amino acids from Thr387 to His485 of DAB486-IL-2 increases both the potency and the apparent dissociation constant (Kd) of the resulting fusion toxin for high affinity interleukin-2 receptor bearing target cells. In contrast, the inframe deletion of either the 191 amino acids between Asp291 and Gly483 or the 85 amino acids between Asn204 and Ile290 results in a 1000-fold loss in potency. These regions contain the putative membrane-spanning regions and the amphipathic membrane surface-associating regions of fragment B, respectively. These results indicate that the efficient delivery of the ADP-ribosyltransferase from DAB486-IL-2 to the cytosol requires the membrane-associating domains of fragment B. This function has been postulated to play a role in the diphtherial intoxication of eukaryotic cells. However, unlike native diphtheria toxin, fragment B sequences distal to Thr387 do not enhance the potency of DAB486-IL-2. PMID- 2195028 TI - Superoxide dismutase undergoes proteolysis and fragmentation following oxidative modification and inactivation. AB - Red blood cells (RBC) are thought to be well protected against oxidative stress by the antioxidant, cu-pro-zinc enzyme superoxide dismutase (CuZn SOD) which dismutates O2- to H2O2. CuZn SOD, however, is irreversibly inactivated by its product H2O2. Exposure of intact RBC to H2O2 resulted in the inactivation (up to 50%) of endogenous SOD in a concentration-dependent manner. When RBC were exposed to O2- and H2O2, generated by xanthine + xanthine oxidase, an even greater loss of SOD activity (approximately 75%) was observed. Intracellular proteolysis was markedly increased by exposure to these same oxidants; up to a 12-fold increase with H2O2 and a 50-fold increase with xanthine oxidase plus xanthine. When purified SOD was treated with H2O2, inactivation of the enzyme also occurred in a concentration-dependent manner. Accompanying the loss of SOD activity, the binding of the copper ligand to the active site of the enzyme diminished with H2O2 exposure, as evidenced by an increase in accessible copper. Significant direct fragmentation of SOD was evident only under conditions of prolonged exposure (20 h) to relatively high concentrations of H2O2. Gel electrophoresis studies indicated that under most experimental conditions (i.e. 1-h incubation) H2O2, O2-, and H2O2 + O2- treated SOD experienced charge changes and partial denaturation, rather than fragmentation. The proteolytic susceptibility of H2O2 modified SOD, during subsequent incubation with (rabbit, bovine or human) red cell extracts also increased as a function of pretreatment with H2O2. Both enzyme inactivation and altered copper binding appeared to precede the increase in proteolytic susceptibility (whether measured as an effect of H2O2 concentration or as a function of the duration of H2O2 exposure). These results suggest that SOD inactivation and modification of copper binding are prerequisites for increased protein degradation. Proteolytic susceptibility was further enhanced by H2O2 exposure under alkaline conditions, suggesting that the hydroperoxide anion is the damaging species rather than H2O2 itself. In RBC extracts, the proteolysis of H2O2-modified SOD was inhibited by sulfhydryl reagents, serine reagents, transition metal chelators, and ATP; suggesting the existence of an ATP independent proteolytic pathway of sulfhydryl, serine, and metalloproteases, and peptidases. The proteolytic activity was conserved in a "Fraction II" of both human and rabbit RBC, and was purified from rabbit reticulocytes and erythrocytes to a 670-kDa proteinase complex, for which we have suggested the trivial name macroxyproteinase. In erythrocytes macroxyproteinase may prevent the accumulation of H2O2-modified SOD.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2195029 TI - Structure-function relationship in spinach ferredoxin-NADP+ reductase as studied by limited proteolysis. AB - Studies of limited proteolysis on purified ferredoxin-NADP+ reductase with various proteases were performed in the presence and absence of the flavoprotein ligands. Both the diaphorase and the ferredoxin-dependent activities of the enzyme were followed as well as the proteolytic pattern in sodium dodecyl sulfate polyacrylamide gel electrophoresis, with further characterization of the polypeptides produced. These experiments revealed that only two regions of the flavoprotein are susceptible to the attack of the proteases used: (a) the N terminal chain which can be cleaved only up to Lys35 and (b) the sequence segment 235-250. It can be inferred that these regions are on the surface of the protein molecule and presumably have a very flexible conformation adaptable to the protease active site. The deletion of the N-terminal region up to Thr36 of the native reductase (Mr 35,000) produced a truncated form (Mr about 31,000) which had full diaphorase activity but lost the capacity to catalyze the ferredoxin dependent reaction. Proteolytic cleavage at the 235-250 segment of the sequence yielded a nicked protein (Mr about 30,000 by gel filtration; 23,000 plus 7,000 in denaturing electrophoresis) devoid of both activities. Protection by the flavoprotein ligands implies that the 23-35 region of the sequence is part of the binding site for ferredoxin and the 235-250 polypeptide segment is in the NADP(+) binding site. PMID- 2195030 TI - Expression of the alpha, beta II, and gamma protein kinase C isozymes in the baculovirus-insect cell expression system. Purification and characterization of the individual isoforms. AB - Detailed in vitro comparisons of the biochemical characteristics of three protein kinase C isozymes were performed. As an alternative to earlier uncertain separation methods and expression schemes, highly purified and genetically distinct protein kinase C enzymes were produced using the baculovirus expression system. The baculovirus expression system yielded approximately 200-300 micrograms of the purified isozyme from 3 x 10(8) (100 ml of culture medium) baculovirus-infected insect cells. Biochemical characterization of the expressed isozymes indicated that the three isozymes had virtually indistinguishable Ca2+, Mg2+, and ATP dependencies. However, in certain critical functional characteristics such as phosphatidylserine dependencies, phospholipid and substrate preferences, and arachidonic acid activation, the gamma isozyme exhibited distinctive properties when compared with both the alpha and beta II subtypes. In addition, the activity of the beta II subtype was more dependent upon diacylglycerol or phorbol esters for activation than either the alpha or gamma isoforms. The alpha isozyme, unlike the beta II and gamma forms, was totally dependent on Ca2+ for activation in the presence of free arachidonic acid. These studies provide definitive characterizations of the pure isoforms; many of the findings were consistent with earlier enzymatic observations using hydroxyapatite-purified isoforms. Thus, the distinctive biochemical properties of the protein kinase C isozymes are consistent with the hypothesis that each isoform may have distinct roles in signal transduction processes. PMID- 2195031 TI - Expression and assembly of mature apotransacylase (E2b) of bovine branched-chain alpha-keto acid dehydrogenase complex in Escherichia coli. Demonstration of transacylase activity and modification by lipoylation. AB - A cDNA clone encoding the entire transacylase (E2b) precursor of the bovine branched-chain alpha-keto acid dehydrogenase complex (Griffin, T. A., Lau, K. S., and Chuang, D. T. (1988) J. Biol. Chem. 263, 14008-14014) was used to construct a prokaryotic expression vector for recombinant mature E2b. The overexpression in Escherichia coli correlates with the presence near the 5'-terminus of the mature E2b coding region (nucleotides 20 to 28) of the sequence 5'-TCAAACT-CT-3'. It has been proposed that this sequence is involved in secondary mRNA recognition through interaction with the 5'-terminus of the bacterial 16 S rRNA. The mature E2b protein has transacylase activity when assayed with exogenous dihydrolipoamide and [1-14C] isovaleryl-CoA as substrates. However, the recombinant protein has no attached lipoic acid. This was established by the absence of radiolabel incorporation when transformed E. coli cells were grown in a medium containing DL-[2-3H]lipoic acid. The recombinant mature E2b protein was purified to greater than 95% purity in one step using Sepharose 4B column chromatography. The purified recombinant protein was shown to have a cubic 24-mer structure by electron microscopy and to possess a specific activity similar to that of the purified natural bovine E2b. The purified recombinant mature E2b was lipoylated in vitro in the presence of 2 mM ATP using a mitochondrial extract prepared from bovine liver. The above results provide the first evidence that the proper folding and assembly of mature bovine E2b is independent of the attachment of lipoyl moieties and that mammalian lipoylation activity is present in mitochondria. PMID- 2195032 TI - Digital subtraction arthrography of the wrist. AB - Digital subtraction arthrography of the wrist was used to identify abnormalities in eighty-six (60 per cent) of 139 patients during a fifteen-month period. Multiple abnormalities were noted in thirty-four (25 per cent) of the wrists. The clinical signs and symptoms in the eighty-six wrists did not always correlate with the defects that were seen on the arthrograms. Three of five patients who had an isolated tear of the scapholunate ligament, six of thirteen who had an isolated tear of the lunotriquetral ligament, and seven of nineteen who had an isolated tear of the triangular fibrocartilage complex also had signs and symptoms on the opposite side of the wrist. Many of the lesions that were seen on arthrography may have been serendipitous, degenerative, or unrelated to a specific injury. There was a high prevalence of positive ulnar variance in patients who had at least one ulnar abnormality. Capsular tears, most often seen on the radiovolar aspect of the wrist, were best outlined by contrast medium injected into the radiocarpal joint. The arthroscopic findings differed from the arthrographic findings in five of the twenty patients in whom both studies were done. The three-compartment technique of injection is a valuable diagnostic tool. Injections of contrast medium into the distal radio-ulnar joint outlined five of thirteen tears of the triangular fibrocartilage complex that were not seen after injection into the radiocarpal joint. Of the eleven tears that were seen after injection into the radiocarpal joint, five were not seen when contrast medium was injected into the distal radio-ulnar joint. PMID- 2195033 TI - Vascularity of the posterior tibial tendon. AB - Operative exploration of ruptures of the posterior tibial tendon has revealed a relatively constant site of damage just posterior and distal to the medial malleolus. It has been hypothesized that the stress that is applied to the tendon as it passes under the medial malleolus may compromise the vascularity of the tendon in this area, a process that is similar to that described for the supraspinatus tendon. In order to evaluate this possibility, we studied the vascularity of the posterior tibial tendon. We injected twenty-eight cadaveric limbs with an India ink-gelatin mixture and cleared them using a modified Spalteholz technique. The gross external and internal vascularity were drawn, and the specimens were photographed. The vascularity of the tendons was noted to be abundant at the osseous insertion and the musculotendinous function of the tendon. There was a zone of hypovascularity posterior and distal to the medial malleolus in all specimens. The results of this study suggest that relative avascularity and resulting degenerative changes may be predisposing factors in rupture of the posterior tibial tendon, and that they have important implications in terms of the operative management of the rupture. PMID- 2195034 TI - Orthopaedic aspects of fragile-X syndrome. AB - Fragile-X syndrome is one of the most common inherited forms of mental retardation. An associated connective-tissue disorder involving elastin accounts for the most frequent musculoskeletal manifestations, which include severe flexible flat feet, excessive laxity of the joints, and scoliosis. At our institution, seventy-five (50 per cent) of the 150 male patients who had fragile X syndrome had flat feet, eighty-five (57 per cent) had excessive laxity of the joints, and ten had scoliosis. Twenty-nine of the patients who had flat feet had been evaluated or treated, or both, by an orthopaedic surgeon before the diagnosis of fragile-X syndrome had been made. Only one of these patients had been referred for developmental and genetic evaluation, which suggests that the orthopaedic community is not familiar with this syndrome. The orthopaedist should consider the diagnosis of fragile-X syndrome in the evaluation of a mentally retarded boy or man who has a family history of mental retardation. The presence of flat feet and excessive laxity of the joints, associated with the characteristic facies, macro-orchidism, and behavior, justifies a referral for developmental and genetic evaluation. Early diagnosis is important for several reasons, including genetic counseling for the family, more efficacious medical treatment, and specialized education. PMID- 2195035 TI - Outer gloves in orthopaedic procedures. Cloth compared with latex. AB - A randomized prospective study was undertaken to determine the rate of punctures of the inner glove when techniques of double-gloving were employed for orthopaedic operations. Group I consisted of twenty-five procedures in which double latex gloves were used, and Group II comprised another twenty-five in which latex inner gloves and cloth outer gloves were worn. As the outer glove was expected to act as a barrier against puncture of the inner glove, only inner gloves were tested. All glove exchanges done intraoperatively for presumed tears of the inner glove were noted, as were punctures of the skin. The type and length of the procedure were also documented. Group I (double latex gloves) had a significantly higher rate of total inner-glove perforations per procedure (p less than 0.0001) than Group II (cloth and latex gloves). Furthermore, unrecognized perforations were significantly higher in Group I than in Group II (p less than 0.01). In Group I, the number of punctures increased with the duration of the operation; a puncture was found in all procedures in which the operation lasted longer than three hours (p less than 0.01). In Group II, only two tears of the inner glove occurred. Both were unrecognized and were independent of the duration of the operation. PMID- 2195036 TI - Scheuermann disease. PMID- 2195037 TI - A test of microtubule translocation during neurite elongation. AB - In a previous study using PC-12 cells (Lim, S. S., P. J. Sammak, and G. G. Borisy, 1989. J. Cell Biol. 109:253-263), we presented evidence that the microtubule component of the neuronal cytoskeleton is differentially dynamic but stationary. However, neurites of PC-12 cells grow slowly, hindering a stringent test of slow axonal transport mechanisms under conditions where growth was substantial. We therefore extended our studies to primary cultures of dorsal root ganglion cells where the rate of neurite outgrowth is rapid. Cells were microinjected with X-rhodamine-labeled tubulin 7-16 h after plating. After a further incubation for 6-18 h, the cells were photobleached with an argon ion laser. Using a cooled charged couple device and video microscopy, the cells were monitored for growth of the neurite and movement and recovery of fluorescence in the bleached zone. As for PC-12 cells, all bleached zones in the neurite recovered their fluorescence, indicating that incorporation of tubulin occurred along the neurite. Despite increases in neurite length of up to 70 microns, and periods of observation of up to 5 h, no movement of bleached zones was observed. We conclude that neurite elongation cannot be accounted for by the transport of a microtubule network assembled only at the cell body. Rather, microtubules turn over all along the length of the neurite and neurite elongation occurs by net assembly at the tip. PMID- 2195038 TI - CDC42 and CDC43, two additional genes involved in budding and the establishment of cell polarity in the yeast Saccharomyces cerevisiae. AB - Budding in the yeast Saccharomyces cerevisiae involves a polarized deposition of new cell surface material that is associated with a highly asymmetric disposition of the actin cytoskeleton. Mutants defective in gene CDC24, which are unable to bud or establish cell polarity, have been of great interest with regard to both the mechanisms of cellular morphogenesis and the mechanisms that coordinate cell cycle events. To gain further insights into these problems, we sought additional mutants with defects in budding. We report here that temperature-sensitive mutants defective in genes CDC42 and CDC43, like cdc24 mutants, fail to bud but continue growth at restrictive temperature, and thus arrest as large unbudded cells. Nearly all of the arrested cells appear to begin nuclear cycles (as judged by the occurrence of DNA replication and the formation and elongation of mitotic spindles), and many go on to complete nuclear division, supporting the hypothesis that the events associated with budding and those of the nuclear cycle represent two independent pathways within the cell cycle. The arrested mutant cells display delocalized cell-surface deposition associated with a loss of asymmetry of the actin cytoskeleton. CDC42 maps distal to the rDNA on chromosome XII and CDC43 maps near lys5 on chromosome VII. PMID- 2195039 TI - Isolation of a functional vesicular intermediate that mediates ER to Golgi transport in yeast. AB - We have used an in vitro assay that reconstitutes transport from the ER to the Golgi complex in yeast to identify a functional vesicular intermediate in transit to the Golgi apparatus. Permeabilized yeast cells, which serve as the donor in this assay, release a homogeneous population of vesicles that are biochemically distinct from the donor ER fraction. The isolated vesicles, containing a post ER/pre-Golgi form of the marker protein pro-alpha-factor, were able to bind to and fuse with exogenously added Golgi membranes. The ability to isolate fusion competent vesicles provides direct evidence that ER to Golgi membrane transport is mediated by a discrete population of vesicular carriers. PMID- 2195040 TI - Development of a cell-free system to study the membrane assembly of photosynthetic proteins of Rhodobacter capsulatus. AB - A cell-free translation system from the facultatively photoheterotrophic bacterium Rhodobacter capsulatus is described. Synthesis of two proteins of the bacterium's photosynthetic apparatus (light-harvesting complex B870 alpha and beta) was performed by SP6 polymerase transcription of the subcloned genes, isolation of the mRNA and translation in vitro using a cell-free extract of R. capsulatus cells. The integration of these proteins in vitro into added intracytoplasmic membrane vesicles (ICM) is demonstrated. Without addition of ICM approximately 70% of the synthesized B870 proteins were soluble. If, however, ICM were present during synthesis, the majority of the soluble protein was found to associate with the membranes. The membrane-associated polypeptides could be solubilized only by detergent treatment but could not be extracted by treatment at alkaline pH (Na2CO3), suggesting that the proteins had been firmly inserted into the lipid bilayer. Moreover, the B870 alpha and beta proteins that integrated in vitro into ICM were also found to associate with pigment ligands and to assemble into a native reaction center/B870 complex. The native conformation of this complex isolated from ICM by Triton fractionation was demonstrated by microspectral analysis of the bound pigments. PMID- 2195041 TI - c-Ha-rasVal 12 oncogene-transformed NIH-3T3 fibroblasts display more decondensed nucleosomal organization than normal fibroblasts. AB - We have compared the nucleosomal organization of c-Ha-rasVal 12 oncogene transformed NIH-3T3 fibroblasts with that of normal fibroblasts by using micrococcal nuclease (MNase) as a probe for the chromatin structure. The bulk chromatin from asynchronously and exponentially growing ras-transformed cells was much more sensitive to MNase digestion than chromatin from the normal cells. Southern hybridization analyses of the MNase digests with probes specific for the ornithine decarboxylase (odc) and c-myc genes showed that the coding and/or 3' end regions of these growth-inducible genes carry a nucleosomal organization both in ras-transformed and normal cells. Studies with cells synchronized by serum starvation showed that in both cell lines the nucleosomal organization of chromatin is relatively condensed at the quiescent state, becomes highly decondensed during the late G1 phase of the cell cycle, and starts again to condense during the S phase. However, in ras-transformed cells the decondensation state stayed much longer than in normal cells. Moreover, irrespective of the phase of the cell cycle the bulk chromatin as well as that of the odc and c-myc genes was more sensitive to MNase digestion in the ras-transformed cell than in the normal fibroblast. Decondensation of the chromatin was also observed in the normal c-Ha-ras protooncogene-transfected cells, but to a lesser extent than in the mutant ras-transformed cells. Whether the increased degree of chromatin decondensation plays a regulatory role in the increased expression of many growth related genes in the ras-transformed cells remains an interesting object of further study. PMID- 2195042 TI - Nuclear and cytoplasmic localization of different basic fibroblast growth factor species. AB - The subcellular distribution of basic fibroblastic growth factor (bFGF) was analyzed by subcellular fractionation and immunofluorescence to gain insight into potential mechanisms for its release from cells. Subcellular fractionation of either SK-Hep-1 cells or NIH 3T3 cells transfected with a bFGF cDNA revealed that the 18 kd form of bFGF was found primarily in the cytosolic fraction, whereas the 22 and 24 kd forms of bFGF were found preferentially in ribosomal and nuclear fractions. Analysis of bFGF distribution by immunofluorescence using an antibody that recognized all forms of bFGF indicated both cytoplasmic and nuclear localization but failed to reveal any growth factor in structures representing secretory vesicles. Therefore, bFGF has a distribution inconsistent with that of a secretory protein. PMID- 2195043 TI - Effect of epidermal growth factor on the expression of protooncogenes c-myc and c Ha-ras in short-term primary hepatocyte culture. AB - We have characterized the effect of the hepatomitogen epidermal growth factor (EGF) on the expression of the cellular protooncogenes c-Ha-ras and c-myc in short-term (48 hours) primary hepatocyte culture. mRNA concentrations of both protooncogenes increased dramatically in nonproliferating cultures and in the absence of EGF, suggesting that the isolation procedure or the culture conditions may trigger expression of these genes or potentially increase the lifetime of transcripts in vitro, regardless of the presence of a mitogen. In cells treated with EGF, a distinct peak in c-Ha-ras expression was seen 24 hours after EGF treatment. This coincided with the onset of DNA synthesis. No such peak was seen in cultures not treated with EGF. The c-myc mRNA concentrations were increased relatively equally in all cultures with or without the addition of EGF. These data show a differential response of these two cell-cycle-associated genes to the culture conditions and EGF stimulation. It also demonstrated that enhanced gene expression for Ha-ras and myc in hepatocytes can occur in the absence of cell proliferation. PMID- 2195044 TI - Acquisition of a lysosomal enzyme by myoblasts in tissue culture. AB - Skeletal muscle myoblasts from different sources acquired high levels of the lysosomal enzyme beta-glucuronidase, when they were cultured together with mitogen-activated lymphocytes. Immunofluorescent staining, thermal stability, and electrophoretic mobility showed that the increase in enzyme activity in the myoblasts was due to the presence of the lymphocyte form of the enzyme. Although myoblasts were able to take up exogenous beta-glucuronidase from the culture medium by mannose 6-phosphate receptor-mediated endocytosis, enzyme acquisition during co-culture with lymphocytes was independent of this pathway. Enzyme transfer from the lymphocytes was found to require direct cell-cell contact with the muscle cells, and was accompanied by an increase in beta-glucuronidase activity in the lymphocytes themselves. Since this additional activity was also due to the presence of the lymphocyte form of the enzyme, these results indicate that interaction with the muscle cells induced the de novo synthesis of beta glucuronidase in the lymphocytes. PMID- 2195046 TI - Caring for the caregiver. PMID- 2195045 TI - Studies on the role of basic fibroblast growth factor in vivo: inability of neutralizing antibodies to block tumor growth. AB - Affinity-purified polyclonal rabbit antibodies prepared against recombinant basic fibroblast growth factor (bFGF) neutralized the ability of bFGF to stimulate plasminogen activator (PA) production and endothelial cell migration in vitro. After iodination and intraperitoneal injection of the antibodies in mice, approximately 76% of the maximum circulating level of 125I-anti-bFGF antibodies (AF) was found as intact IgG after 24 hr. Furthermore, the circulating 125I-AF retained the ability to bind bFGF. Studies were performed to determine whether the growth of three different murine tumors (CT26, EHS, or B16/BL6) could be inhibited with affinity-purified neutralizing antibodies against bFGF. Tumors were injected subcutaneously in syngeneic mice, and neutralizing antibodies against bFGF were injected daily into the peritoneum. All studies, which varied in tumor burden, antibody dose, and study length, indicated that neutralizing antibodies against bFGF had no effect on tumor size, tumor growth, or tumor histology. PMID- 2195047 TI - Career development: an integrated process. PMID- 2195048 TI - Channeling and other esoteric methods of self-care. PMID- 2195049 TI - Healing the spirit. PMID- 2195050 TI - Social/behavioural pharmacy in the United States--the state-of-the-art. PMID- 2195051 TI - Long-term therapeutic efficacy with once-daily isosorbide-5-mononitrate (Imdur). PMID- 2195052 TI - The Seventh Jack Tizard Memorial Lecture. Aspects of adoption. AB - Adoption has a long history and there has been a change in traditional assumptions and practice. It is now seen as a form of child care, one of a spectrum of resources for children in need. Adopted children generally show a good outcome but are over-represented in clinical populations. This trend is likely to continue as older children with histories of severe deprivation, neglect, abuse and institutionalization are placed. New light has been thrown on "telling" in adoption by developmental studies. Adoption disruption increases with age and other factors at placement, requiring further research into its origins and management. PMID- 2195053 TI - Maternal directiveness in interactions with mentally handicapped children: an analytical commentary. AB - Maternal directiveness is portrayed as a negative interactional phenomenon in the mental retardation literature. Based on the speculation that a directive interactional style is causally related to poor developmental outcomes, the reduction of maternal directive behaviour is becoming a major thrust in early intervention work. This paper questions the characterization of directiveness as an inherently negative interactional phenomenon and highlights limitations in our current understanding of directiveness. Critical issues requiring attention in future research are identified and early interventionists cautioned that management of maternal directive behaviour must be founded on sound, empirically validated principles. PMID- 2195054 TI - A controlled crossover trial of fenfluramine in autism. AB - We report a 12 month double-blind randomized crossover trial of fenfluramine in 20 children with the syndrome of autism. On active drug most of the children lost weight and blood serotonin levels fell by an average of 60%. There was a fall in urinary dopamine (DA) and noradrenaline (NA) levels and increased excretion of homovanillic acid (HVA). Some of the children showed improvement in tests of cognitive and language function, although the results did not achieve overall statistical significance. Event-related brain potentials (ERPs) were obtained in seven subjects on an auditory choice reaction time task. Side effects of the drug included irritability and lethargy. Fenfluramine may have a limited place in the management of some patients with autistic disorder. PMID- 2195055 TI - A human IgG 3 is opsonic in vitro against type III group B streptococci. AB - Preparations of IgG 3 isolated by absorption of IgG 1, IgG 2, and IgG 4 from a human iv immunoglobulin with protein A-Sepharose were evaluated for their opsonic activities against type III group B streptococcal (GBS) strains. The resulting preparations were free of IgG 1 and IgG 2 and contained only trace amounts of IgG 4 (less than 2% of total IgG). These IgG 3 preparations exhibited excellent opsonic activities against type III GBS strains, similar to those of the unfractionated iv immunoglobulin (based on total IgG concentrations in the opsonic assays). In contrast, preparations of IgG 1, 2, and 4 eluted from protein A-Sepharose with 2 M acetic acid and 7 M urea were significantly less effective in enhancing phagocytosis and killing of type III GBS than IgG 3 preparations or iv immunoglobulin. The reasons for excellent opsonic activity of IgG 3 preparations as well as for decreased opsonic activity of IgG 1, 2, and 4 preparations are not clear. Perhaps alteration of IgG by lower pH and high concentrations of urea may have impaired the functional activity of IgG 1, 2, and 4 preparations. The significant finding of this study is the first demonstration of the excellent opsonic activity of IgG 3, emphasizing the importance of having intact IgG 3 in commercial immunoglobulin preparations used in prophylaxis or treatment of GBS infections. PMID- 2195056 TI - [Current status of IgA nephritis and its etiological study]. PMID- 2195057 TI - [Treatment and future problems of acute leukemia]. PMID- 2195058 TI - Pulmonary surfactant and its apoproteins. PMID- 2195059 TI - Expression of the potent vasoconstrictor endothelin in the human central nervous system. AB - Endothelin is a potent vasoconstrictive peptide initially characterized as a product of endothelial cells. To examine the potential role of endothelin as a neuropeptide, we studied its distribution in the human central nervous system. RNA blot hybridization provided evidence of endothelin gene transcription in a variety of functional regions of the brain. In situ hybridization confirmed the widespread pattern of endothelin transcription and indicated that the highest density of cells containing endothelin mRNA is in the hypothalamus. This technique localized endothelin transcription to cells of the nervous system as well as the vascular endothelium. Immunocytochemical studies detected endothelin immunoreactivity in neurons, providing evidence of the synthesis of the peptide in this cell type and confirming that endothelin is a neuropeptide. Although the prominent expression of endothelin in the hypothalamus may indicate a central vasoregulatory role for the peptide, the widespread distribution of endothelin in neurons in other areas of the brain implies a more fundamental role in the regulation of nervous system function. PMID- 2195060 TI - Impaired vasodilation of forearm resistance vessels in hypercholesterolemic humans. AB - The effect of hypercholesterolemia on vascular function was studied in humans. To eliminate the potential confounding effects of atherosclerosis, vascular reactivity was measured in the forearm resistance vessels of 11 normal subjects (serum LDL cholesterol = 111 +/- 7 mg/dl) and 13 patients with hypercholesterolemia (serum LDL cholesterol = 211 +/- 19 mg/dl, P less than 0.05). Each subject received intrabrachial artery infusions of methacholine, which releases endothelium-derived relaxant factor, and nitroprusside which directly stimulates guanylate cyclase in vascular smooth muscle. Maximal vasodilatory potential was determined during reactive hyperemia. Vasoconstrictive responsiveness was examined during intra-arterial phenylephrine infusion. Forearm blood flow was determined by venous occlusion plethysmography. Basal forearm blood flow in normal and hypercholesterolemic subjects was comparable. Similarly, reactive hyperemic blood flow did not differ between the two groups. In contrast, the maximal forearm blood flow response to methacholine in hypercholesterolemic subjects was less than that observed in normal subjects. In addition, the forearm blood flow response to nitroprusside was less in hypercholesterolemic subjects. There was no difference in the forearm vasoconstrictive response to phenylephrine in the two groups. Thus, the vasodilator responses to methacholine and nitroprusside were blunted in patients with hypercholesterolemia. We conclude that in humans with hypercholesterolemia, there is a decreased effect of nitrovasodilators, including endothelium-derived relaxing factor, on the vascular smooth muscle of resistance vessels. PMID- 2195061 TI - A neuropathic deficit, decreased sweating, is prevented and ameliorated by euglycemia in streptozocin diabetes in rats. AB - Decreased sweating, especially of feet and legs, occurs in human diabetic neuropathy. It might be studied in experimental diabetes to characterize it, elucidate its mechanisms, and determine whether it can be prevented or treated. The pilocarpine-induced sweat responses (SR) in the hind foot pads of groups of control and streptozocin diabetic rats, in good (GC) and in poor (PC) glycemic control and with a crossover design after 20 wk of diabetes, were evaluated with the silicone mold sweat test to determine the number of sweat droplets per group of foot pads. The SR was dose dependent and reproducible. The SR disappeared with denervation and reappeared with reinnervation; denervation hypersensitivity did not develop. In the GC group, euglycemia was achieved by regulating the caloric intake and using multiple daily injections of Ultralente insulin. The SR was not different from that of the control group for up to 136 d. In the PC group, the SR became abnormal (P less than 0.005) at 16 d and progressively worsened: 40% of baseline values at 14 wk (P less than 0.001). After restoring euglycemia in the PC group, a normal SR occurred at 12 d. These results show that one human neuropathic deficit, failure of sweating, can be prevented or ameliorated by good glycemic control. PMID- 2195062 TI - Human growth hormone prevents the protein catabolic side effects of prednisone in humans. AB - Prednisone treatment causes protein wasting and adds additional risks to a patient, whereas human growth hormone (hGH) treatment causes positive nitrogen balance. To determine whether concomitant administration of hGH prevents the protein catabolic effects of prednisone, four groups of eight healthy volunteers each were studied using isotope dilution and nitrogen balance techniques after 7 d of placebo, hGH alone (0.1 mg.kg-1.d-1), prednisone alone (0.8 mg.kg-1.d-1), or prednisone plus hGH (n = 8 in each group). Whether protein balance was calculated from the leucine kinetic data or nitrogen balance values, prednisone alone induced protein wasting (P less than 0.001), whereas hGH alone resulted in positive (P less than 0.001) protein balance, when compared to the placebo treated subjects. When hGH was added to prednisone therapy, the glucocorticoid induced protein catabolism was prevented. Using leucine kinetic data, negative protein balance during prednisone was due to increased (P less than 0.05) proteolysis, whereas hGH had no effect on proteolysis and increased (P less than 0.01) whole body protein synthesis. During combined treatment, estimates of proteolysis and protein synthesis were similar to those observed in the placebo treated control group. In conclusion, human growth hormone may have a distinct role in preventing the protein losses associated with the administration of pharmacologic doses of glucocorticosteroids in humans. PMID- 2195065 TI - Psychobiological differences in childhood stress response. II. Cardiovascular markers of vulnerability. AB - A fuller understanding of the distribution of morbidity in childhood may be achieved through the study of individual differences in stress susceptibility. The importance of person-environment transactions has been appreciated in the psychological domain, but only recently have individual differences in children's psychobiological responsivity to the environment become the focus of systematic study. Current work on individual differences in children's biobehavioral stress response is illustrated by reviewing current research on two aspects of cardiovascular regulation: cardiovascular reactivity and cardiac vagal tone. Both show promise of being stable individual traits emerging early in childhood, and both have correlates with children's patterns of health, behavior, and development. Consideration of individual differences in children's physiological responsivity can enrich our understanding of the meaning and adaptive significance of childhood behavior. PMID- 2195064 TI - Epithelial basement membrane of mouse jejunum. Evidence for laminin turnover along the entire crypt-villus axis. AB - Little is known regarding turnover of the epithelial basement membrane in adult small intestine. Are components degraded and inserted along the length of the crypt-villus axis or selectively in the crypt region with subsequent migration of basement membrane from crypt to villus tip in concert with epithelium? We injected affinity-purified sheep anti-laminin IgG or sheep anti-laminin IgG complexed to horseradish peroxidase (HRP) into mice to label basement membrane laminin in vivo. Fluorescence microscopy revealed linear fluorescence along the length of the jejunal epithelial basement membrane 1 d after anti-laminin IgG injection. By 1 wk, small nonfluorescent domains were interposed between larger fluorescent domains. Over the next 5 wk the lengths of nonfluorescent domains increased progressively whereas those of fluorescent domains decreased. Additionally, electron microscopy revealed HRP reaction product along the length of the epithelial basement membrane after 1 d whereas unlabeled or lightly labeled domains that increased in length with time were observed interposed between heavily labeled domains by 2 and 4 wk along the entire crypt-villus axis. We conclude that laminin turnover occurs focally in the epithelial basement membrane of mouse jejunum along the crypt-villus axis over a period of weeks and that this basement membrane does not comigrate in concert with its overlying epithelium. PMID- 2195063 TI - The 210-kD nuclear envelope polypeptide recognized by human autoantibodies in primary biliary cirrhosis is the major glycoprotein of the nuclear pore. AB - We have recently reported a new family of nuclear autoantibodies in a subset of patients with primary biliary cirrhosis. These antibodies bind to a nuclear envelope polypeptide(s) of approximately 200 kD, the exact identity of which was not established. In this study, we show that all of these autoantibodies are directed against a 210-kD integral membrane glycoprotein of the nuclear pore. PMID- 2195066 TI - Controlled study of the impact of educational home visits by pharmacists to high risk older patients. AB - Lack of information about medications coupled with high rates of utilization complicates compliance with medication regimens and increases the risk of adverse effects among older adults. We undertook a study of the efficacy of community based interventions by pharmacists in a randomly-allocated one-half of a sample of 284 older adults considered to be at high risk for medication-related problems. Information and attitudes towards prescription and over-the-counter medications did not differ significantly between the intervention and comparison groups, either before or after the pharmacist interventions. However, visits to physicians were significantly less in the intervention group, suggesting an important if unexpected impact on health-related behavior. PMID- 2195067 TI - Morphology and immunoperoxidase studies of intestinal adenomatosis in the blue fox, Alopex lagopus. AB - In a blue fox farm about 300 of 400 weanling pups were affected with diarrhoea and prolapse of the rectum. About 40 pups died in an emaciated state after a few days of disease. Eight pups were submitted for examination. Pathological findings were restricted to the caecum, proximal colon and rectum, with occasional extension to the ileum. Affected areas revealed a thick and rigid intestinal wall, a narrow lumen and a thickened, wrinkled and sometimes ulcerated mucosa. Histologically, the mucosa showed long tortuous crypts outlined by a high pseudostratified epithelium which lacked goblet cells. Epithelial cells revealed increased basophilia, and mitoses were seen along the entire crypt length and in the surface epithelium. Silver impregnation showed curved organisms in the apical cytoplasm of the altered epithelial cells. Penetration of the muscularis mucosa by the altered epithelial cells was frequent. The avidin-biotin-immunoperoxidase complex (ABC) technique revealed positive organisms in the apical cytoplasm of altered epithelial cells, when rabbit antisera against different biotypes and serotypes of Campylobacter jejuni and Campylobacter coli were used. Antisera against Campylobacter sputorum subsp. muscosalis and Campylobacter hyointestinalis were negative. PMID- 2195069 TI - Superficial thrombophlebitis. II. Secondary hypercoagulable states. AB - Secondary hypercoagulable states are complex clinical conditions associated with an increased risk of thrombosis in which the exact pathophysiology is poorly understood. Secondary causes of superficial thrombophlebitis include malignancy, pregnancy, use of oral contraceptives, infusion of prothrombin complex concentrates, Behcet's disease, Buerger's disease, Mondor's disease, infectious agents, conditions that promote venous stasis, intravenous catheters and intravenous drug use. Conditions that may stimulate superficial thrombophlebitis include dermatophyte cellulitis at saphenous phlebectomy sites, sarcoidal granulomas, cutaneous polyarteritis nodosa, and hyperalgesic pseudothrombophlebitis in patients who test positive for human immunodeficiency virus. The distinguishing features, clinical evaluation, treatment, and histologic characteristics of the various disorders are reviewed. PMID- 2195068 TI - Intestinal and pulmonary mycotic lymphadenitis in cattle. AB - Among 4877 slaughtered cattle with tuberculosis-like lesions in lymph nodes, 94 cases (1.9 per cent) revealed fungal hyphae on histopathological examination. The survey period was 12 years and most of the affected animals (greater than 77 per cent) were beef cattle. Affected nodes were mesenteric in 84 cases (89.4 per cent), mediastinal and/or bronchial in seven cases (7.4 per cent), and in three cases (3.2 per cent), both mesenteric and mediastinal nodes were affected. The incidence of mycotic lymphadenitis was unrelated to year of study or season. Eighty-two of the cases were re-examined histologically and immunohistochemically. All lesions were granulomatous in nature and, in 26 cases, eosinophilic asteroid bodies (rosette formation) around hyphae were found. In 75 cases, immunofluorescence staining identified the agent as a zygomycete, probably Absidia corymbifera and, in one case, there was a concurrent infection with a Candida species. In seven cases that did not react with the antibodies employed, a diagnosis of zygomycosis was suggested on the basis of hyphal morphology. Hyphae of Aspergillus spp. were not found in any of the lesions. A concurrent fungal and mycobacterial infection (M. avium) was diagnosed in one case. Thus, zygomycetes are the main cause of macroscopically apparent mycotic lymphadenitis, a sporadic disease most probably caused by feeding with mouldy food stuffs. PMID- 2195070 TI - How fingerprints came into use for personal identification. AB - The use of fingerprints for personal identification became widespread early in this century. How the fingerprints slowly became standardized involves many persons, including Nathaniel Grew, Johannes Purkinje, William Herschel, Henry Faulds, Charles Darwin, Francis Galton, Mark Twain, Juan Vucetich, Edward Henry, and J. Edgar Hoover. Although fingerprints have been noted and used since antiquity, a 25-year burst of activity that secured adoption of their use for identification began in about 1880. New modifications and applications have continued to the present. The history of fingerprints offers an excellent example of how society adopts innovations. This story also includes a bitter struggle for appropriate credit for various crucial steps in developing and adopting this important tool. More recent technical advances, including computers and molecular biology, now supplement the ease and usefulness of fingerprints, although the word fingerprinting continues in use by metaphoric extension. PMID- 2195071 TI - Azathioprine hypersensitivity in bullous pemphigoid. PMID- 2195072 TI - Eugene M. Farber, MD. PMID- 2195073 TI - Subfascial lipoma of the forehead. PMID- 2195074 TI - Epithelioid angiomatosis in patients with AIDS. Report of seven cases and review of the literature. AB - Seven cases of a distinctive vascular proliferation in patients with acquired immunodeficiency syndrome are discussed and compared with other reported cases. All cases share clinical and pathologic manifestations that can be recognized early. Warthin-Starry-positive bacilli within some of the lesions and their response to erythromycin may indicate that the proliferation is associated with an infectious agent, possibly the bacillus that causes cat-scratch disease. PMID- 2195076 TI - Drug administration to the pregnant or lactating woman: a reference guide for dermatologists. AB - Dermatologists are occasionally faced with the problem of appropriate systemic drug administration to the lactating or pregnant woman. The physician's responsibility is to be aware of the potential risk of prescribing a specific therapeutic agent, to inform the mother of this risk, and to administer an alternate, less deleterious drug, if available. The purpose of this review is to provide guidelines for dermatologists who must consider the risks to the fetus or neonate of drug administration to the pregnant woman or lactating mother. PMID- 2195075 TI - The heterogeneity of Jessner's lymphocytic infiltration of the skin. Immunohistochemical studies suggesting one form of perivascular lymphocytoma. AB - Seventeen patients (six women and 11 men) with Jessner's lymphocytic infiltration of the skin were studied. Nineteen biopsy specimens were analyzed with the following monoclonal antibodies: UCHL1 (T cells), 4KB5, L26 (B cells), LN1 (germinal center B cells), and BerH2 (Ki-1+ cells). Routine direct immunofluorescence was performed on 15 specimens. In 10 of 19 specimens both B and T cells were demonstrated; the B cells were in close proximity to small blood vessels. In 50% of these cases the B cell component expressed LN1 positivity. We use the term perivascular lymphocytoma to describe this pattern. Nine specimens showed T cells only. No Ki-1+ cells were detected. Routine immunofluorescence studies were performed on 15 specimens. In six of seven specimens in which there was a mixed cell population of B and T cells, results were completely negative. In contrast, six of the remaining eight specimens with a predominantly T cell population revealed weak, patchy, granular, positive labeling for immunocomponents, particularly IgM and C3 at the basement membrane. These findings suggest that Jessner's lymphocytic infiltration is a heterogeneous disorder with at least two separate immunophenotypes. The finding of perivascular follicular center differentiation in more than half the specimens suggests a possible relationship in these cases to other benign lymphoid hyperplasias (pseudolymphomas). PMID- 2195077 TI - Intramammary challenge of the bovine mammary gland with coliform bacteria during early involution. AB - Isolates of Escherichia coli (n = 12), Klebsiella pneumoniae (n = 20), and Klebsiella oxytoca (n = 10) were used to challenge involuting mammary glands at 7 d of the dry period. Bacteria were selected for challenge on the basis of their ability to grow in a pooled source of dry cow secretion obtained at 21 d of involution. Challenge bacteria were classified as highly adapted (in vitro growth greater than 7 cfu log10/ml) or poorly adapted (growth less than 2 cfu log10/ml) for growth in dry cow secretion. Intramammary infusion of Escherichia coli, K. pneumoniae, and K. oxytoca resulted in 0, 40, and 30%, respectively, of quarters infected. Isolates highly adapted for growth in dry cow secretion caused 75% of K. pneumoniae and 67% of K. oxytoca experimental intramammary infections. Results indicated that the ability to overcome inhibitory properties of dry cow secretion was related to the establishment of K. pneumoniae and K. oxytoca intramammary infections in the dry gland. There was no evidence that growth of E. coli in dry cow secretion related to pathogenicity in the dry gland. Experimental challenge using multiple isolates did confirm the resistance of the involuting mammary gland to E. coli infection. PMID- 2195078 TI - Responses of dairy cows in early lactation to bovine somatotropin and ruminally inert fat. AB - Bovine somatotropin (0 or 41.2 mg/d bST) and calcium salts of long-chain fatty acids (0 or .77 kg/d Ca-LCFA) were administered to 16 Holstein cows in early lactation. Cows remained on 0 or 41.2 mg/d bST for the entire 10 wk and received 0 or .77 kg/d Ca-LCFA in one of two 5-wk periods. Production data were recorded daily, milk fatty acids, and blood metabolites were determined once each period. Treatments did not affect feed intake. Fat-corrected milk (kg/d) and percentage of milk fat for cows receiving no supplementation, fatty acids alone, bST alone, and fatty acids and bST together were 33.8, 3.2; 33.5, 3.1; 37.4, 3.4; and 40.8, 3.5. Milk fatty acids below C16 were reduced with either bST or dietary fatty acids; C16 fatty acids were lower with bST but higher with dietary fatty acids; C18:0 fatty acids were reduced with dietary fatty acids; and C18:1 fatty acids were higher with either bST or dietary fatty acids. Blood acetoacetate concentrations were higher with both bST and dietary fatty acids, beta hydroxybutyrate was not different, and FFA and insulin concentrations increased with bST. In this experiment, the energy supplied by Ca-LCFA acids enhanced the lactogenic effect of bST. PMID- 2195079 TI - Psychotherapy process research: progress, dilemmas, and future directions. AB - The first several decades of psychotherapy process research have produced advances in measure development and substantive findings of process-outcome relations. A recent paradigm shift toward sequentially patterned, significant change episodes is described, emphasizing segmentation of process by meaningful patterns wherever they occur. Theoretical, psychometric, and data analytic dilemma are reviewed. Strategies are offered that may enhance future research efforts. These include greater attention to construct validity of measures, the relation of process to phase-specific outcome criteria, and the continuing development of multivariate data analytic strategies that take into account Patient X Treatment interactions as well as the sequential dependency of process data. The development of a national archive of significant change events is recommended to advance modeling of the change process, segmentation, construct validation of measures, integration of qualitative and quantitative approaches, and development of a cross-theoretical language for therapy process. PMID- 2195080 TI - Issues and methods in psychotherapy process research. AB - Some of the problems and issues that have characterized process research in psychotherapy are discussed, as is the complexity of research that attempts to combine process and outcome adequately. The diversity of topics studied, the variety of scales used, the individual theoretical constructs investigated, the investigation of single process variables, and the relative lack of replication have made integration of findings difficult. It is suggested that more than one therapeutic orientation be studied in a specific project in order that some type of control be included. Although statistically significant correlations between selected process variables and measures of outcome have been secured, proof of causality remains to be demonstrated. PMID- 2195081 TI - Theory-based research for understanding the process of dynamic psychotherapy. AB - Research is reviewed on 6 theoretical propositions central to psychodynamic psychotherapy: (1) The establishment of an alliance is important to successful outcome; (2) the patient displays a central relationship theme (transference); (3) transference interpretations are helpful; (4) the therapist aims at accurate interpretations of the transference; (5) the patient gains understanding of self and the relationship pattern; and (6) the patient's improvement is reflected in changes in the relationship pattern, although the pattern is still evident. We suggest concepts that are in need of research development: internalization, resistance, working through, self-understanding and insight, and the therapist's adherence to recommended techniques. PMID- 2195082 TI - Exploratory in-session process research in individual psychotherapy: a review. AB - The goal of exploratory process research is to describe what occurs within psychotherapy sessions, eventually leading to the development of theories based on the accumulation of replicated results. Several areas in which exploratory methods are currently being used are described: therapist techniques, client behavior, covert processes, process models, interactions between therapists and client, and therapy events. Additionally, several areas in which exploratory methods would be useful for future research are described: the links between client personality characteristics, therapy process, and outcome; the timing and quality of therapist interventions; and client readiness for the therapist interventions. PMID- 2195083 TI - Interrelating research processes of process research. AB - Given the contextual boundedness of process variables, 3 assumptions implicit in present process research are questioned: Process variables (a) have fixed meanings, (b) discretely contribute to outcomes, and (c) have a decontextualized net worth, evaluated by their correlations with outcomes. From a systemic perspective, a conceptual framework is suggested that integrates both theory driven and discovery-oriented strategies into a cyclical, ecologically oriented model. Experiments, observations of change events, and detailed descriptions partake in this cyclical model, informing and enriching each other. The core of this integration is a transactional conception that sees change processes as mutually defining rather than interacting with each other, thus leading to holistic examinations of changes of pattern in addition to patterns of change. The transactional core serves as the point of departure and home base for both theory-driven and discovery-oriented research strategies. PMID- 2195084 TI - Intrinsic and extrinsic motivation for smoking cessation. AB - An intrinsic-extrinsic model of motivation for smoking cessation was evaluated with 2 samples (ns = 1.217 and 151) of smokers who requested self-help materials for smoking cessation. Exploratory and confirmatory principal components analysis on a 36-item Reasons for Quitting (RFQ) scale supported the intrinsic-extrinsic motivation distinction. A 4-factor model, with 2 intrinsic dimensions (concerns about health and desire for self-control) and 2 extrinsic dimensions (immediate reinforcement and social influence), was defined by 20 of the 36 RFQ items. The 20-item measure demonstrated moderate to high levels of internal consistency and convergent and discriminant validity. Logistic regression analyses indicated that smokers with higher levels of intrinsic relative to extrinsic motivation were more likely to achieve abstinence from smoking. PMID- 2195085 TI - Mode-specific effects among three treatments for depression. AB - In the NIMH Treatment of Depression Collaborative Research Program (TDCRP), 250 depressed outpatients were randomly assigned to interpersonal psychotherapy, cognitive-behavioral therapy, imipramine plus clinical management, or pill placebo plus clinical management treatments. Although all treatments demonstrated significant symptom reduction with few differences in general outcomes, an important question concerned possible effects specific to each treatment. The therapies differ in rationale and procedures, suggesting that mode-specific effects may differ among treatments, each of which was precisely specified, applied appropriately, and shown to be discriminable. Outcome measures were selected for presumed sensitivity to the different treatments. Findings provided only scattered and relatively insubstantial support for mode-specific differences. None of the therapies produced consistent effects on measures related to its theoretical origins. PMID- 2195086 TI - Hypothesis validity of clinical research. AB - Hypothesis validity refers to the extent to which research results reflect theoretically derived predictions about the relations between or among constructs. The role of hypotheses in theory testing is discussed. Four threats to hypothesis validity are presented: (a) inconsequential research hypotheses, (b) ambiguous research hypotheses, (c) noncongruence of research hypotheses and statistical hypotheses, and (d) diffuse statistical hypotheses and tests. PMID- 2195087 TI - Isolation and culture of panning method-enriched Langerhans cells from dispase dissociated epidermal cells of the mouse. AB - Langerhans cells (LCs) are bone marrow-derived, Ia-positive antigen-presenting cells in the epidermis which constitute 2-4% of the total epidermal cells. We examined the usefulness of a combination of dispase treatment and the panning method for enriching and culturing mouse LCs. Trunk skin was treated with partially purified dispase (Godo Shusei, type II) to separate epidermal sheets and to dissociate epidermal cells. Suspended cells were treated with ascites or culture supernatant containing anti-Ia monoclonal antibody, and LCs were enriched by the Ia-mediated panning method. Per mouse, 3-4 X 10(5) LCs were recovered with greater than 95% purity and greater than 90% viability. Enriched LCs potently stimulated the allogeneic mixed-leukocyte reaction. Ultrastructural observations revealed that enriched LCs contained many vesicles but almost no Birbeck granules. A laminal structure, which was apparently adhesive to the surface of LCs, was observed when ascites were employed as the anti-Ia antibody. These results indicate that a combination of dispase treatment and the Ia-mediated panning method is very useful for isolating high yields of functionally mature murine Langerhans cells with high purity and viability. PMID- 2195088 TI - Cutaneous T cell lymphoma differing from classical mycosis fungoides and Sezary syndrome: clinical, histological and immunohistochemical studies of six cases. AB - Six cases of cutaneous T cell lymphoma (CTCL), differing from classical mycosis fungoides (MF) and Sezary syndrome (SS), were studied. Initial skin eruptions were erythematoplaques, papules and tumors. Some cases showed frequent spontaneous regressions without any specific therapy; however, the prognosis was not always good. Surface phenotypes of neoplastic cells were markedly heterogeneous from the onset of initial skin eruption. Three cases expressed the T helper/inducer (Th/i) phenotype, one case had both the Th/i and T suppressor/cytotoxic phenotypes, and the other two cases lacked both surface markers. These results suggest that CTCL other than MF and SS displays marked heterogeneous clinical behavior and diverse morphological and immunophenotypical characteristics of the postthymic T cells. PMID- 2195089 TI - Ultrasonography of proliferative vascular lesions of the skin. AB - High-resolution ultrasonography with small part probes was performed on 20 proliferative vascular lesions of the skin (3 lymphangiomas, 9 hemangiomas, 8 Kaposi sarcomas). All the lesions were submitted to histological examination. The histological cuts were made in the same planes as the ultrasound scans in order to obtain a direct comparison. The sonographic pattern of each histotype is characteristic and correlated with the corresponding histological picture. Lymphangiomas appear as large anechoic communicating cavities; hemangiomas have small hypoechoic areas separated by thin hyperechoic septa. Kaposi sarcomas possess a mixed sonographic structure with ill-defined margins. Ultrasound is proposed as a simple and harmless diagnostic aid to clinical examination of proliferative vascular lesions of the skin. PMID- 2195090 TI - Nursing models in a special hospital: a critical analysis of efficacity. AB - Models of care from the general field of nursing applied in special hospitals appears to be unworkable in this type of environment in terms of their inability to affect patient care. It is argued that these external models, adopted due to a crisis of confidence in special hospitals, fail because their fundamental constructs clash with that of the institution's particular sociology. A historical analysis of the development of special hospitals and nursing models reveals a dichotomy of emergent values, highly complex in nature, which conflict from the notion of Parsonian role-adoption. From this position, it is suggested that the strength of value systems are such that this leads to a non-negotiable stalemate of forensic elements of client and institution, and the 'treatment' ethic as prescribed by the medicalization of criminology. This article critically analyses the six most commonly-used nursing models in special hospitals and pinpoints the areas of breakdown within this type of environment from a sociological perspective. Finally, it argues for a new direction away from 'generalist' ideals of nursing towards a theoretical construction of 'specialism' in forensic care. PMID- 2195091 TI - 70th anniversary year: Part II. The ACD becomes a catalyst for significant changes in organized dentistry. PMID- 2195092 TI - Salt taste preferences and perceptions of elderly and young adults. AB - Current research has yielded both support and refutation for the theory that elderly adults have lower taste acuity. The present study compared the perception of and preference for salt in persons 65 years and over and in persons aged 20 to 35 years. The subjects were free-living, had not been hospitalized in the past 12 months, and had never been on a sodium-restricted diet. Salt was introduced in suprathreshold concentrations of 0.3%, 0.5%, 0.7%, and 0.9% in mashed potatoes and chicken broth. The 48 older adults in our study demonstrated higher preferences for the four salt concentrations in the potatoes (p = .0001) and the broth (p = .0004) than did the 53 younger adults. There were no significant differences in the two age groups' abilities to perceive the saltiness of the four concentrations. There were also no significant differences in salt perception among subgroups identified for age, gender, smoking behavior, and denture use. Both groups correctly ranked the concentrations in ascending order. Our study found that taste acuity for salt in older subjects was not different from that of younger adults when suprathreshold concentrations of salt in mashed potatoes and chicken broth were used as stimuli. PMID- 2195093 TI - Productivity measurement in foodservice: past accomplishments--a future alternative. AB - Productivity measurement, monitoring, and improvement are ongoing management responsibilities. Financial and personnel resources are limited, and foodservice managers are faced with the increasingly difficult task of efficiently and effectively meeting consumer demands. A wide variety of labor productivity measures have been reported in the foodservice literature. The most prevalent of those measures include labor minutes per meal and labor minutes per meal equivalent. A measurement technique that considers only one or a few of the resources used to produce goods and services may result in limitations and potentially inaccurate productivity measurement. A total-factor productivity model that relates organizational output to all input resources is recommended. Such a model has been used in several business firms. Aggregate and multiple partial-factor productivity ratios enabled business managers to identify the relationships and trade-offs among all resources not previously revealed in labor productivity measures. Such an expanded productivity model could be applied in food-service settings to provide additional information for enhanced decision making. PMID- 2195094 TI - Modulable Southern and Northern blot hybridization apparatus for routine screening of gene amplification and expression. AB - An apparatus for Northern and Southern blot hybridization is described. It allows from one to twenty-four blots to be processed at the same time, with different probes. All the pre-, post- and hybridization steps are performed without handling the filters and the experimenter is totally protected from beta radiations. The development of such modulable materials has become necessary since Southern and Northern techniques are becoming routine assays in hospitals, particularly in the field of oncology, in prognosis and for hereditary diseases, as an antenatal diagnosis procedure. PMID- 2195095 TI - Purification of human liver fumarylacetoacetase using immunoaffinity chromatography. AB - A method is described to purify fumarylacetoacetase from crude human liver extracts using immunoaffinity chromatography. Immobilized rabbit antibodies specific for beef liver fumarylacetoacetase were used as an immunoadsorbent. With this rapid and specific procedure human liver fumarylacetoacetase could be purified to apparent homogeneity. The molecular weight of native human liver fumarylacetoacetase is approximately 83000 as estimated by gel filtration. The two subunits have a molecular weight of approximately 41000, as determined by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Purified human liver fumarylacetoacetase has a broad pH optimum with a maximum at pH 7.2 and a Km = 2.1 microM towards fumarylacetoacetate. PMID- 2195096 TI - Plasma clearance of heterogeneous growth hormone components in the rat: effects of diabetes and starvation. AB - Two forms of immunoreactive rat GH (rGH), bit rGH (b.rGH) and little rGH (l.rGH) are predominant in both pituitary and plasma from control (C), fasted (F), food restricted (FR), diabetic (D) and insulin-treated D (D +l) rats. The l.rGH appears to be the predominant form in plasma and pituitary in all five experimental groups. However, in each group, the relative proportion of b.rGH in plasma exceeds from that in pituitary. To determine whether these differences are due to a delayed metabolic clearance of the big component, the MCRs and distribution volume of b.rGH, l.rGH and total rGH were measured in C, F, FR, D and D + l rats. Pituitary extracts, b.rGH and l.rGH were injected as a bolus, and the disappearance of each component was followed by RIA. In each group, the MCR of the big form was significantly lower than that of total rGH and l.rGH. Moreover, MCRs of total rGH, b.rGH and l.rGH in F and D rats were lower than that of the corresponding component in C animals. The decreased b.rGH MCR in each experimental group, and that of total rGH, b.rGH and l.rGH in F and D animals, is associated with a lower distribution space for the above cited components. Furthermore, the reduced receptor-binding activities for the larger form of rGH, and the loss of hepatic GH receptors in D rats, together with the possibility that b.rGH could be presumably excluded from the glomerular filtration and subsequent degradation, may be reasons for the longer persistence of b.rGH in plasma in each experimental group, and for prolonged permanence of l.rGH in plasma in F and D rats. PMID- 2195097 TI - The growth hormone response to growth hormone releasing hormone in patients previously treated with bilateral adrenalectomy alone for Cushing's disease. AB - Human growth hormone releasing hormone (GHRH) fails to stimulate human growth hormone (GH) in hypercortisolism. In order to study whether the responsiveness to GHRH stimulation returns after cure of the hypercortisolism, the GH response to GHRH was examined in 8 patients at least 5 yr after they had undergone bilateral adrenalectomy as their sole treatment for Cushing's disease. None had current evidence of a pituitary macroadenoma. A group of 8 healthy subjects matched for age and sex formed the control group. All patients and subjects received an iv injection of GHRH 1 microgram/kg, after an overnight fast, blood samples were taken before and at 15, 30, 45, 60, 90 and 120 min. There was no statistical difference between the peak GH or area under curve (AUC) response (median, range) in the two groups studied (adrenalectomized peak GH 9.2 (4.6-32.0) vs 16.5 (7.5 63) mU/l, adrenalectomized AUC response 647.5 (344.2-1489.5) vs 1103.5 (339.7 5188.5) mU/l. Patients with Cushing's disease once cured of hypercortisolism, have a GH response to GHRH. PMID- 2195098 TI - Long term growth hormone (GH)-releasing hormone and biosynthetic GH therapy in GH deficient children: comparison of therapeutic effectiveness. AB - Twenty-five GH-deficient children were treated with GHRH (1-44), once daily sc for 6-24 months. At the 6th month of therapy, 40% of our patients showed a catch up growth (responders), while the remaining 60% did not (nonresponders). No differences in auxological and biological variables at inclusion were found between the two groups. However, integrated GH secretion elicited by iv GHRH at inclusion was significantly (p less than 0.025) higher in responders than in non responders. During GHRH therapy, no significant increase in IGF 1/SmC was found in both groups. In all patients treatment was discontinued after 6-24 months, when its effect on growth rate failed. After a wash-out period of at least 6 months, patients were submitted to biosynthetic GH therapy. After 6 months of GH treatment a significant catch-up growth was found in both responder and non responder children. Although the majority of GH-deficient children have hypothalamic rather than pituitary dysfunction, GHRH therapy is found to be less effective than GH treatment. Other methods of GHRH administration are worth investigating. PMID- 2195099 TI - The glucose clamp technique for the study of patients with hypoglycemia: insulin resistance as a feature of insulinoma. AB - Occurrence of hypoglycemia during a prolonged fasting, accompanied by inappropriately high serum insulin levels, is considered a reliable index of the presence of insulinoma. Previous in vitro studies on insulin receptors, and in vivo hyperinsulinemic clamps have shown that patients with insulinoma are insulin resistant. In the present study 10 patients with insulinoma, 6 patients with nontumoral (also called functional or reactive hypoglycemia) hypoglycemia and 6 normal subjects were fasted for 24 h and their blood glucose levels were maintained constant by means of a programmed glucose infusion (isoglycemic glucose clamp) delivered by an artificial pancreas (Biostator). Blood glucose levels were monitored in continum, glucose infused (M) and glucose clearance (MCR) were evaluated at hourly intervals, and serum insulin (IRI) levels were evaluated every 6 h. Blood glucose levels were higher in controls than in patients with insulinoma and in patients with non tumoral hypoglycemia; M, MCR and IRI were progressively higher in controls, in patients with nontumoral hypoglycemia and in patients with insulinoma. The M/I index (M divided by IRI levels, an index of insulin sensitivity) was lower in patients with insulinoma than in other subjects and patients, indicating the existence of insulin resistance. These data indicate that: i) patients with insulinoma require large amounts of glucose to remain isoglycemic during a prolonged fast; ii) insulin resistance is a common feature of insulinoma and can be shown even under near physiologic conditions such as a 24-h fasting. The present study does not clarify whether insulin resistance occurs at the hepatic level or at other, peripheral levels. PMID- 2195101 TI - Nonenzymatic glycosylation, the Maillard reaction and the aging process. PMID- 2195102 TI - The use of triazolam in older patients with periodic leg movements, fragmented sleep, and daytime sleepiness. AB - Many studies have shown a relationship between fragmented nocturnal sleep and daytime sleepiness. In the current study, 11 patients, aged 55-75, were identified with fragmented nocturnal sleep secondary to periodic leg movements and objective daytime sleepiness as verified by the Multiple Sleep Latency Test (MSLT). In a double-blind, repeated measures, cross-over design, patients had three nights of treatment with placebo, 0.125 mg of triazolam, or 0.25 mg of triazolam following an adaptation night. Although total leg movements were not changed, the medication increased total sleep time and sleep efficiency while decreasing the number of stage changes. Generally, daytime performance and objective alertness were significantly improved following the use of triazolam. It was concluded that acute use of triazolam, particularly the 0.125 mg dose, could improve sleep and daytime function in older patients with periodic leg movements, fragmented sleep, and daytime sleepiness. PMID- 2195100 TI - Critical reappraisal of the clinical effectiveness of different methods of assisted fertilization. PMID- 2195103 TI - Next steps in describing aging and disease in longitudinal studies. AB - Longitudinal studies have contributed much to the understanding of aging. Traditionally, age-specific changes in physiological functioning are inferred from studies in which persons with disease processes believed to be relevant to the function in question are excluded from the results. The main theme of this review is that, in the future, studies of aging must better attempt to capture the interplay between disease and aging processes. A variety of research results, mostly from the Baltimore Longitudinal Study of Aging, are used to support this argument. Topics covered include: the role of longitudinal studies in aging research; the complexity of the aging process; the significance of cohort and secular changes for understanding both aging and disease processes; age changes over the adult life span in the significance of risk factors for disease; and age related increases in morbidity in a longevous group of men. PMID- 2195104 TI - Is blood pressure an important variable in research on aging and neuropsychological test performance? AB - Regression analyses using Blood Pressure, Age, and the multiplicative effect of Blood Pressure and Age as predictors of performance (on selected tests from the Halstead-Reitan neuropsychological test battery) were done. Three hypotheses were tested with subjects ranging in age from 20 to 72 years of age: (1) blood pressure values predict neuropsychological test performance over a wide range of hypertensive and normotensive blood pressure values; (2) blood pressure predicts performance within the narrower range of normal and borderline values; (3) blood pressure X age interactions, when observed over this age and education range, are such that negative blood pressure effects on performance are larger for younger than older subjects. Regression analyses confirmed each of these hypotheses and indicated that strength of prediction was not reduced when participants free from hypertension-related complications and medication were tested. Blood pressure X age interactions were seen for Trailmaking-B Test and the Tactile Performance Test-Localization for the primary sample. However, only Blood Pressure main effects were observed for the Average Impairment Rating, the Categories Test, TPT Memory and TPT-Localization when age, sex, and education were controlled. Implications of these findings for the role of blood pressure in aging research and for longitudinal studies with subjects free from the need for treatment with antihypertensive medications are discussed. PMID- 2195105 TI - Do single nucleotide mutations result in clinically significant changes in hepatitis B virus pathogenicity? PMID- 2195106 TI - Branched chain enriched amino acid versus glucose treatment of hepatic encephalopathy. A double-blind study of 65 patients with cirrhosis. AB - We studied the effects of infusion of a branched chain enriched amino acid mixture versus glucose on acute hepatic encephalopathy in patients with cirrhosis. Sixty-five patients were randomly treated with 1 g/kg per day of an amino acid mixture with 40% branched chain contents (32 patients), or isocaloric glucose (33 patients) for a maximum of 16 days. The regimens further included glucose infusion to a total of 26.5 kcal/kg per day and lactulose. The patients took part in the study for 5-6 days. In each group 17 patients woke up. In the amino acid group eleven died and four developed renal failure. In the glucose group ten died, three developed renal and two respiratory failure, and one remained encephalopathic. The coma score worsened in three of the patients who died in the amino acid group, but in all patients who died in the glucose group. The negative nitrogen balance on entry reversed in the amino acid group, but not in the glucose group. Thus, the branched chain enriched amino acid supplement did not change the prognosis for wake-up, but had other effects on the cerebral state and on nitrogen homeostasis. PMID- 2195107 TI - Decreased hepatocellular volume and intact morphology of tight junctions in calcium deprivation-induced cholestasis. Stereological and multiple indicator dilution analysis. AB - Cholestasis induced by perfusion of the liver with hypocalcemic media has been ascribed to several defects in bile secretion including increased biliary permeability. To investigate this model of cholestasis further, livers perfused with hypo- and normocalcemic media were examined stereologically using thin sections and freeze-fracture replicas. Organization of tight junctions was not altered by hypocalcemia; neither the number of strands nor the junctional depth were significantly affected. By contrast, the volume of hepatocytes decreased by 11% (p less than 0.001), compensated for by an increase in the space of Disse and of the sinusoids. The canalicular length decreased by 25% (p less than 0.01), while the canalicular membrane surface was not altered. Multiple indicator dilution studies confirmed a decrease in hepatocellular volume, measured as the water space by 14% (p less than 0.03). This was compensated for by an increase in the extravascular sucrose, but not the albumin space. Immediately after switching from normo- to hypocalcemic perfusate a K+ efflux of 62 mumol/g liver was observed corresponding to approx. 8% of the hepatocellular water space. Our results suggest that hypocalcemia-induced cholestasis is due, at least in part, to a disturbance of the osmotic equilibrium, possibly caused by impairment of an ion transport system involved in hepatocellular volume control. PMID- 2195109 TI - The value of Doppler US in the study of hepatic hemodynamics. Consensus conference (Bologna, Italy, 12 September, 1989). PMID- 2195110 TI - Chronic active hepatitis associated with vitiligo, nail dystrophy, alopecia and a new variant of LKM antibodies. AB - In this report we describe the case of a 7-year-old boy, suffering from autoimmune-type chronic active hepatitis (AI-CAH) associated with vitiligo, nail dystrophy, alopecia areata and a variant of liver kidney microsomal (LKM) autoantibodies. This patient's antibodies are different from LKM-1 which are directed against cytochrome P450 db1. They react predominantly with perivenous hepatocytes in contrast to LKM-1 antibodies which homogeneously stain the whole liver lobule in immunofluorescence. In Western blot analysis this LKM variant reacts with a liver microsomal protein of approx. 50 kDa, but not with recombinant LKM-1 (cytochrome P450 db1) antigen. Immunosuppressive treatment led to a normalization of liver histology after 1 year and a significant improvement of vitiligo and alopecia areata. In summary, a case of autoimmune-type chronic active hepatitis is presented which is associated with a new variant of LKM antibodies reacting with a 50 kDa microsomal protein different from cytochrome P450 db1. Furthermore, this patient suffers from extrahepatic syndromes (alopecia, nail dystrophy) that have not been described previously in LKM antibody-positive chronic active hepatitis. PMID- 2195111 TI - Is ethanol per se hepatotoxic? PMID- 2195108 TI - Failure of insulin and glucagon infusion to stimulate liver regeneration in fulminant hepatic failure. AB - A randomised controlled trial of insulin and glucagon infusion was carried out in 18 patients in grade III or IV coma from fulminant hepatic failure due to viral or drug-induced hepatic necrosis to see whether mortality could be reduced by stimulating hepatic regeneration. Nine patients received a continuous infusion of insulin 3 U/h and glucagon 200 micrograms/h made up in 5% dextrose containing 1% human albumin solution (HAS) while controls received 5% dextrose and HAS alone. Baseline plasma insulin and glucagon levels were comparably raised in both groups and, on infusion, rose significantly higher in the insulin- and glucagon-treated patients compared to controls. Two control and one treated patient recovered. Median survival time from enrolment to death was similar for insulin- and glucagon-treated patients and controls--2 and 3 days, respectively. Insulin and glucagon therapy did not enhance hepatic synthetic function, as measured by a fall in prothrombin time or a rise in alpha-fetoprotein; nor did it stimulate hepatic regeneration, only one patient in each group showed histological evidence of hepatic regeneration at post-mortem. PMID- 2195113 TI - Conduct disorder: a review. PMID- 2195112 TI - The use of isolated rat hepatocyte couplets in hepatobiliary physiology. PMID- 2195114 TI - Silicone breast implants--is there cause for concern? AB - Recent controversy has arisen regarding the potential carcinogenesis of medical silicone-gel as used in breast implants. A review of the pertinent literature shows that although rodents do demonstrate the development of sarcomas to any inert material, including silicone-gel, the phenomenon is species specific. No clinical evidence of carcinogenesis in humans has been noted in more than 25 years of use. We conclude that silicone-gel breast implants are safe. PMID- 2195115 TI - A monoclonal antibody raised against Alzheimer cortex that specifically recognizes a subpopulation of microglial cells. AB - A monoclonal antibody (MAb), termed AMC30, was raised after in vitro immunization with sonicated neurofibrillary tangle (NFT)-enriched fractions prepared from Alzheimer's brain. The antigen to which AMC30 is directed was expressed by microglial cells in senile plaques of Alzheimer's disease (AD). Microglia in the parenchyma surrounding brain tumors or infarctions, multinuclear giant cells, perivascular and parenchymal macrophages throughout the brain of AIDS patients were also labeled. Different non-nervous system lesions in which macrophages participate were also stained. Microglial cells in normal areas of the cortex or white matter were not labeled with MAb AMC30. The antigen to which AMC30 is directed was not detected in normal bone marrow, lymph nodes, lung, or spleen monocytes or macrophages. The epitope recognized by MAb AMC30 was present after formalin fixation and paraffin embedding. Our findings suggest that this MAb is directed against an antigen that is specifically expressed in a subpopulation of microglial cells and macrophages reactive to various pathological conditions. PMID- 2195117 TI - High concentrations of bacterial lipopolysaccharide, but not microbial infection induced inflammation, activate macrophage C3 receptors for phagocytosis. AB - Macrophage C3 receptors are normally immobilized in the plane of the cells' plasma membrane and are unable to promote phagocytosis even though they promote avid particle binding. We have previously identified a lymphokine that activates macrophage C3 receptors for phagocytosis both in vitro and in vivo, and others have found that certain types of nonimmunologically mediated inflammation are also able to activate mononuclear phagocyte C3 receptors. These findings raised the possibility that macrophage C3 receptor activation is a universal consequence of inflammation. We sought in the present experiments to determine whether or not inflammation induced by microbial infection in a nonimmune host resulted in activation of macrophage C3 receptors. We injected mice i.p. with either viable microorganisms, microbe-containing immune complexes, or bacterial LPS. Macrophages were harvested by peritoneal lavage 4 days later; nearly all lavage fluids grew the microorganism with which the mouse had been injected, indicating that an infection had been established. Monolayers of macrophages were established and their interaction with sheep E coated with C3 (EIgMC) was determined. All macrophages bound EIgMC, but only macrophages from mice injected with either very high concentrations of LPS or microbe-containing immune complexes ingested them. C3 receptors of macrophages that ingested EIgMC were mobile; others were not. Thus, inflammation induced by microbial infection does not commonly, if at all, activate macrophage C3 receptors; microbe-containing immune complexes and high concentrations of LPS do. The mechanism of receptor activation in each case is C3 receptor mobilization, which is probably mediated by a lymphokine. PMID- 2195116 TI - Inhibition of murine cytotoxic T lymphocyte activity by a synthetic retroviral peptide and abrogation of this activity by IL. AB - A synthetic 17 amino acid peptide (CKS-17) homologous to a highly conserved region of human and animal retroviral transmembrane proteins was investigated for its influence on the generation of murine alloantigen-specific CTL activity in vitro. CKS-17 coupled to a carrier protein, BSA or human serum albumin, inhibited the generation of anti-allo CTL in a dose-dependent manner. Controls consisting of BSA and human serum albumin, which had undergone the coupling procedure or neurotensin, an unrelated peptide, coupled to BSA in an identical manner as CKS 17 showed no such inhibitory action. The suppression was not restricted to the Ag specificity of the CTL activity. CKS-17 exerted inhibitory effects on the early afferent phase of CTL induction. Kinetic studies showed that the suppressive activity occurred when CKS-17 was introduced to the immunologically stimulating culture concomitant with or up to 48 h after initiation of culture. Analysis of the frequency of CTL precursor cells using limiting-dilution assays revealed that CKS-17 did act to reduce the number of precursor cells. Abrogation of the inhibition of CTL activity was observed when IL-2 was introduced to the culture together with the stimulator cells. Other lymphokines, such as IL-4, exerted a similar influence to counteract this suppression. PMID- 2195118 TI - Transcriptional control of c-myc gene expression during stimulation of murine B lymphocytes. AB - The binding of ligand to surface IgR results in the initial activation of B cells. As shown by experiments in which B cells are polyclonally stimulated with anti-Ig antibody, this includes an early increase in c-myc gene expression. In our study a correlation between increases in the rate of gene transcription and the level of c-myc mRNA was observed both with the brief increase in c-myc expression that is induced by anti-Ig, as well as with the more intense and prolonged expression of c-myc that follows treatment with anti-Ig plus the cytoskeleton perturbing agent, cytochalasin. Elevation of the rate of initiation was detected with both stimulatory regimens although the combination of anti-Ig plus cytochalasin increased the rate of elongation in addition to the rate of initiation. These results suggest that stimulation of B lymphocytes alters expression of trans-acting factors that regulate transcription of the c-myc gene. PMID- 2195119 TI - Freeze-fracture electron microscopy of in vitro reconstructed human epidermis. AB - Epidermis has been reconstructed in vitro by seeding human keratinocytes on a human dermal substrate in an air-exposed culture. The end product has been examined by freeze-fracture electron microscopy, transmission electron microscopy (TEM) of thin sections, light microscopy, and lipid analysis using thin-layer chromatography. Light microscopic observation of hematoxylin-eosin stained, paraffin embedded cross-sections of the cell culture revealed a strong resemblance to its intact human counterpart, especially with respect to the morphologic organization in basal, spinous, granular, and horny layers. Freeze fracture electron microscopy and TEM of thin sections generally confirmed the observed resemblances and additionally suggested the presence of lamellar bodies in the stratum granulosum, and of lamellar (lipid) structures between the corneocytes. However, some imperfections were also observed, including some anomalous lipid structures in the intercellular space. Lipid analyses in conjunction with essential fatty acid enrichment studies suggested that the structural anomalies observed in the cultured system may be caused by a lack of linoleyl-ceramides resulting from "immobilization" of linoleyl moieties in the form of triglycerides and phospholipids. In its present form, the air-exposed cell culture already looks very promising as a model for studies of, e.g., skin differentiation disorders such as psoriasis or ichthyosis, studies of the percutaneous penetration and intra(epi)dermal biotransformation of drugs, and skin toxicity screenings. It is furthermore expected that the aforementioned imperfections in the air-exposed cell culture should be avoidable by changing culture conditions such as the relative humidity and the pH, the composition of the medium, or both. PMID- 2195120 TI - Detection of urinary TGF-alpha by HPLC and western blot in patients with melanoma. AB - Transforming growth factor-alpha (TGF-alpha) secretion in the urine may reflect autonomous production by neoplasms. Previous measurements of TGF-alpha in the urine were limited by the large volumes of urine required for detection. Sensitive assays are required to detect TGF-alpha in small urine samples from individual patients with melanoma. An assay which detects ng quantities of immunoreactive TGF-alpha in 10 ml of urine using dialysis, reverse-phase high performance liquid chromatography (HPLC), and Western blot of the HPLC fractions was used to study the urine from 6 melanoma patients and 6 normal human volunteers. No TGF-alpha was detectable in the first voided urine specimens from the normal volunteers. In contrast, TGF-alpha was detected in the urine specimens of two of three patients with primary melanomas and two of three patients with metastatic melanoma. The sensitivity and reliability of the assay were most affected by methods of urine collection, sample preparation, and storage. TGF alpha was less often found in randomly voided urine samples from melanoma patients (1 of 3 detectable) as compared to first voided morning urine samples (3 of 3 detectable). This data indicates urinary TGF-alpha assay may be useful in the diagnosis and management of patients with melanoma. PMID- 2195121 TI - Spinal opioids for the pediatric patient. AB - This article reviews the currently published articles regarding the use of spinal opioids in pediatric patients and discusses the important clinical considerations for the application and monitoring of this technique in children. PMID- 2195122 TI - The development of hand surgery in Great Britain. PMID- 2195123 TI - Pairs of hands. The Hand-March 1969. PMID- 2195124 TI - Imaging the hand and wrist. PMID- 2195125 TI - Diagnostic medical ultrasound in the management of hand injuries. PMID- 2195126 TI - Founders of hand surgery. L.D. Howard. PMID- 2195127 TI - Early active mobilisation following flexor tendon repair in zone 2. PMID- 2195128 TI - Highlights of the Journal of Laboratory and Clinical Medicine, 1955 through 1964. PMID- 2195129 TI - Effect of platelet activation inhibitors on the loss of glycoprotein Ib during storage of platelet concentrates. AB - Platelet membrane glycoprotein Ib (GPIb) in stored platelet concentrates was analyzed by flow cytometry with three separate monoclonal antibodies (AN-51, 6D1, and SZ-2), by tritiated glycoprotein radiolabeling, and by ristocetin-induced agglutination. Flow cytometry showed that a population of surface GPIb-negative platelets was evident at 5 days and increased three- to fivefold by the tenth day. Tritium radiolabeling of surface GPIb showed a decrease over 10 days of 37% +/- 17%. The degree of loss of surface GPIb correlated well with other changes during storage: decreased ristocetin-induced agglutination, decreased responsiveness in the hypotonic shock test, lower plasma pH, and increased extracellular lactic dehydrogenase. Immunoblotting of total platelet GPIb with the SZ-2 antibody showed a decrease of 58% +/- 16% during the 10-day storage period. The effect of protease inhibitors or platelet activation inhibitors on the loss of GPIb during storage was studied in platelet concentrates paired with untreated controls. Only the platelet activation inhibitors prostaglandin E1 and theophylline retarded the loss of surface GPIb levels (93% +/- 5% GPIb remaining vs 65% +/- 16%). Total GPIb levels also decreased less in the presence of the activation inhibitors (45% +/- 22% lost vs 70% +/- 14% lost). These findings suggest that platelet activation, rather than plasma enzymatic activity, is responsible for the loss of platelet GPIb during storage of platelet concentrates. PMID- 2195130 TI - Binding activity and autophosphorylation of the insulin receptor from patients with myotonic dystrophy. AB - To clarify a mechanism of insulin resistance associated with myotonic dystrophy, we studied the insulin receptor by using three different types of cells- circulating erythrocytes, cultured skin fibroblasts, and Epstein-Barr virus(EBV) transformed lymphocytes. In myotonic dystrophy, insulin binding to erythrocytes and fibroblasts was significantly decreased as a result of a reduction of the binding affinity. Insulin binding to EBV-transformed lymphocytes was normal. When the receptors were purified from fibroblasts with wheat germ agglutinin, we could not find a decrease in the binding affinity seen in the intact cells. No difference was observed in the magnitude of basal and insulin-stimulated autophosphorylation of insulin receptors from EBV-transformed lymphocytes between the control and myotonic dystrophy. Southern blot analysis of the insulin receptor gene revealed no restriction fragment length polymorphism associated with myotonic dystrophy. These findings suggest that there is no primary defect of the insulin receptor per se in terms of insulin binding and autophosphorylation in myotonic dystrophy. The reduction of the insulin binding to erythrocytes and fibroblasts may be caused by the plasma membrane abnormality that affects the binding affinity of the receptor. PMID- 2195131 TI - Intrinsic factor studies. II. The effect of gastric juice on the urinary excretion of radioactivity after the oral administration of radioactive vitamin B12. 1953. PMID- 2195132 TI - Poliomyelitis: a historical note. PMID- 2195133 TI - Diagnostic and research applications of electroencephalographic sleep studies in depression. Conceptual and methodological issues. AB - Electroencephalographic sleep studies have become an accepted clinical and research tool in the study of affective disorders, but questions persist regarding their diagnostic utility, sensitivity, and specificity. Several important methodological and conceptual issues are often overlooked in the sensitivity/specificity issue. Appraisals of sleep studies' utility may be affected by the competing needs of clinical and research studies and by focusing too narrowly on the diagnostic use of sleep studies, rather than on their wider clinical and research applications. Examples are presented that demonstrate the utility of sleep studies in examining other aspects of the neurobiology of depression. PMID- 2195134 TI - Characteristics of patients with multiple personality and dissociative disorders on psychological testing. AB - We describe a new psychological testing procedure used on a consecutive series of 14 patients with multiple personality and dissociative disorders who met DSM-III R and research criteria for dissociative disorders. Once dissociative phenomena were accounted for in testing, most patients displayed response patterns markedly different from those of schizophrenic and borderline patients. Patients showed striking variability on cognitive and projective tests, often related to posttraumatic intrusions. Rorschach protocols showed unusual thinking accompanied by psychological complexity and highly developed self-observing capacity. In contrast to classical conceptualizations about these patients, most subjects had personality profiles that were intellectualized, obsessive, and introversive, not histrionic or labile. PMID- 2195135 TI - A phase I-II study on the toxicity and therapeutic efficacy of 5-fluorouracil in combination with leucovorin and cisplatinum in patients with advanced colorectal carcinoma. AB - 5-Fluorouracil (5-FU) has been the treatment of choice for colorectal carcinoma with an overall response rate of about 20%. Recent studies have shown that folate (LV) can increase 5-FU therapeutic efficacy, achieving about a 40% response rate without a clear impact on survival. Cisplatinum (CDDP) is usually inactive in colorectal carcinoma, but the association with 5-FU results in a synergistic antineoplastic effect. A phase I-II study was done to assess the maximally tolerated dose (MTD) of CDDP in association with 5-FU + LV. The MTD for CDDP was 20 mg/m2/wk in association with 5-FU 400-500 mg/m2/wk and LV 500 mg/m2/wk. WHO criteria were used for evaluation of both toxicity and response. In the phase I part we found that the main side-effect in 27 evaluable patients (pts) was gastrointestinal toxicity, mainly in the form of nausea/vomiting (92%) and diarrhea (70%) which caused one therapy-related death. Renal (26%) and marrow (59%) toxicity were acceptable. In the phase II part of the study 1 out of 19 evaluable pts (5%) had a complete response of 309 days, 3 pts achieved a partial response (16%) with a median duration od 410 days, 2 pts had a minimal response (10%) with a median duration of 261 days, and 8 pts experienced no change (42%) with a mean duration of 196 + days. In our opinion the 21% response rate obtained in this series is not satisfactory. Nevertheless the very high number of minimal response + no change patients together with the interesting impact on survival in responders may suggest further phase II-III studies. PMID- 2195136 TI - Fluorouracil and leucovorin for metastatic colorectal cancer. AB - We have performed a prospective randomized controlled study of 5-fluorouracil (5FU) + leucovorin versus 5FU alone in patients with metastatic colorectal cancer. The 5FU at a dose of 370 mg/m2/d x 5 days and the leucovorin at a dose of 200 mg/m2/d x 5 days were given every 28 days. The 5FU dose was escalated to equitoxicity in the single agent arm on subsequent studies. The response rate was 33% for the combination and only 7% for 5FU alone. The median survival for 5FU + leucovorin was 12.6 months and 9.6 months for 5FU alone. The dose-limiting toxicity was mucositis with diarrhea being the second most common problem. The combination of 5FU + leucovorin is an effective treatment in the management of patients with metastatic colorectal cancer and should be used as a foundation from which to build upon. PMID- 2195137 TI - Efficacy and toxicity of 5-fluorouracil and folates in advanced colon cancer. AB - From February 1987 to December 1988, 34 patients with histologically confirmed advanced colorectal carcinoma were entered in a phase II trial with 5 fluorouracil (5-FU) and folinic acid, for evaluation of treatment effectiveness and toxicity. Our data confirmed that the association 5-FU and folates represents an effective and moderately tolerated palliative treatment, with diarrhea being the only dose-limiting toxicity. PMID- 2195138 TI - Biochemical rationale for the 5-fluorouracil leucovorin combination and update of clinical experience. AB - Although 5-fluorouracil has been the drug of choice for the treatment of patients with advanced adenocarcinoma of the colon, the reported response rate dose not exceed 20% with a median survival time less than 9 months. Mechanisms of sensitivity to this agent include: 1) inhibition of thymidylate synthase by FdUMP, the active metabolite of 5-fluorouracil; 2) incorporation of FUTP into cellular RNA; and 3) incorporation of FdUTP into cellular DNA. Recent laboratory preclinical results suggest that the major site of action of 5-fluorouracil when combined with 5-formyltetrahydrofolate (folinic acid, leucovorin) is thymidylate synthase resulting in pronounced and prolonged inhibition of DNA synthesis. This effect is primarily due to the stabilization of FdUMP binding to thymidylate synthase by the reduced folate cofactor, N5, N10-methylenetetrahydrofolate. In this paper, the rationale for the modulation of 5-fluorouracil by leucovorin, the clinical pharmacology and the clinical experience of this combination will be reviewed. PMID- 2195139 TI - Percutaneous retrogasserian glycerol injection in the management of trigeminal neuralgia: long-term follow-up results. AB - The results in 122 patients with trigeminal neuralgia who underwent percutaneous retrogasserian glycerol injection are presented. Eighty patients were followed from 38 to 54 months. The recurrence rate at 54 months was 72% (Kaplan-Meier analysis), and the median pain-free interval was 32 months. Complications associated with the procedure were significantly high: 63% of the patients had definite hypesthesia of the face and 29% had unpleasant dysesthesias, including two cases of anesthesia dolorosa. Sensory disturbances were most frequent in patients who had received a previous alcohol block procedure. Among the patients without previous peripheral procedures, 50% developed sensory disturbances. Because of the high rates of recurrence and sensory disturbances, the authors prefer microvascular decompression for the management of trigeminal neuralgia. PMID- 2195140 TI - CT-guided stereotactic fibrinolysis of spontaneous and hypertensive cerebellar hemorrhage: long-term results. AB - The surgical indication for spontaneous cerebellar hemorrhage is not as controversial as the operative management of intracranial hemorrhage. Timing of the operation is crucial: intervening too early can produce an additional strain on the patient and an increased risk, while waiting too long to evacuate the hematoma can be fatal. This dilemma may be a factor in the relatively high mortality and morbidity rates following both operative and conservative treatment that have been reported in the literature (42.5% and 30%, respectively). In long term studies on 14 patients, the authors have shown that stereotactic puncture and fibrinolysis for cerebellar hemorrhage is a valuable alternative to treatments used currently. The method consists of computerized tomography (CT) guided stereotactic puncture and partial evacuation of the hematoma. After fibrinolysis with urokinase, the residual hematoma can be completely evacuated via a catheter introduced into the cavity of the hematoma. Only one of the 14 patients died in the direct postoperative phase; the remaining patients were enjoying a good to very good quality of life 6 months after the acute event. Two patients subsequently died as a result of pneumonia and cerebral infarction, respectively; both conditions were unrelated to the hemorrhage. The authors conclude that the CT-guided stereotactic method is simple, effective, and safe, and can be applied to patients of any age. PMID- 2195141 TI - Changes in the components and content of biological water in the brain of experimental hydrocephalic rabbits. AB - Changes in biological water components and their respective content in the cortical gray matter and periventricular white matter were studied in rabbits rendered hydrocephalic by intracisternal kaolin injection. There was no change in either total water content or free or bound water content in the cortical gray matter at the various stages of hydrocephalus development. While there was no significant change in total water content in the periventricular white matter at any stage of hydrocephalus, free water content was significantly elevated and bound water content was decreased at the acute and subacute stages, with a return to relatively normal levels at the chronic stage. It is concluded that in the periventricular white matter, free water enters the brain across the ependymal lining during the acute and subacute stages of experimental hydrocephalus with a simultaneous reduction in the bound water and that there is some recovery at the chronic stage. It is suggested that alternative drainage pathways may develop in chronic hydrocephalus allowing drainage of free water in the periventricular white matter, which in turn permits bound water to return to relatively normal levels. PMID- 2195142 TI - Implantation metastasis of pineoblastoma after stereotactic biopsy. Case report. AB - A case is reported of implantation metastasis occurring 2 months after stereotactic biopsy of a pineoblastoma was performed in an 18-month-old child. Although implantation metastasis is well recognized after needle biopsy of solid tumors, it has not been described following stereotactic biopsy of a brain tumor. Implications for the role of stereotactic biopsy in the management of brain tumors is discussed. PMID- 2195143 TI - FDA panel discussion on cadaver dura. PMID- 2195144 TI - Changes in free amino acid levels in various tissues of common carp in response to insulin injection followed by force-feeding an amino acid diet. AB - The effects of a single injection of porcine insulin on free amino acid levels in plasma, erythrocytes, hepatopancreas and skeletal muscle were simultaneously monitored in common carp; the fish were force-fed a complete diet composed of crystalline amino acids as the sole protein precursors (amino acid diet) to study the dynamics of amino acid metabolism. The force-feeding of the amino acid diet caused surges in the concentrations of almost all amino acids in fish injected with saline, and amino acid levels reached peaks within 1 h in plasma as well as in hepatopancreas. It took more than 2.5 h for most amino acids to reach maximum levels in erythrocytes and skeletal muscle of the same fish. The injection of insulin stimulated drastic reductions of free amino acid levels in the plasma. At the same time, it facilitated reduction of free amino acid levels without elevating glutamine and ammonia levels in erythrocytes, hepatopancreas or skeletal muscle. These results suggest that exogenous insulin accelerated assimilation of dietary free amino acids and their deposition in these tissues. PMID- 2195145 TI - High fat feeding increases brown fat GDP binding in lean but not obese Zucker rats. AB - The effects of high fat feeding on brown fat thermogenesis in rodents are controversial. In this study, we examined the effects of 8 d of high fat feeding on brown fat mitochondrial GDP binding (an in vitro index of thermogenic activity) in lean (Fa/?) and obese (fa/fa) Zucker rats. Six-week-old female rats were fed a defined low fat control diet (9.5% of energy from fat) only during the dark cycle (1200-2400 h), and food intake was measured daily at 1200, 1600, 2300, and 2400 h for 7 d (the control period). For the next 8 d, half of the lean and obese rats were fed a high fat diet (65% of energy from fat), and the others remained on the low fat control diet. Each rat was fed the amount of energy equivalent to its average energy intake during the 7-d control period. Rats were killed at 0800-1000 h. In the lean rats, high fat feeding increased GDP binding. This increased binding in the lean rats appeared to reflect levels of dietary fat and carbohydrate and was independent of caloric intake. The blunted GDP binding of the obese rats failed to respond to dietary changes. PMID- 2195146 TI - Regulation of rat liver branched-chain alpha-keto acid dehydrogenase activity by meal frequency and dietary protein. AB - Effects of feeding frequency on liver branched-chain alpha-keto acid dehydrogenase (BCKAD) activity are unknown. In the present study, rats were trained to consume their daily allotment of food in 6 h (meal-feeding). Rats were fed diets containing 0, 9, 25 or 50% casein and after 10 d were killed before or 3 h after the meal. The enzyme in rats fed diets containing 0, 9 and 25% casein was activated three- to sixfold after meal consumption. Previous studies showed that the liver enzyme is essentially fully activated in post-absorptive rats fed an adequate protein diet ad libitum. Meal-feeding an adequate protein (25% casein) diet resulted in a marked decrease in the postabsorptive percentage of active complex compared to ad libitum feeding of the same diet (29 +/- 6% vs. 93 +/- 6% active). Administration of alpha-ketoisocaproate (200 mumol/100 g body weight, an inhibitor of BCKAD kinase) reversed the meal-feeding-induced inactivation of the complex within 10 min. We conclude that the frequency of food intake, in addition to the level of dietary protein, influences the proportion of liver BCKAD in the active state. Inactivation of hepatic BCKAD in rats trained to feed once a day may be an adaptive mechanism that results in increased efficiency of branched-chain amino acid utilization between meals. PMID- 2195147 TI - Nursing shortage bibliography. PMID- 2195148 TI - Abortive cryptophthalmos: a case report and a review of cryptophthalmos. AB - Cryptophthalmos is a rare, probably autosomal recessive condition in which the lid folds fail to separate in the embryo resulting in a continuous sheet of skin from the forehead to the cheeks covering the eyes. Cryptophthalmos has many variants and is usually associated with multiple other congenital anomalies. This article reports on an isolated case of "abortive cryptophthalmos" with multiple systemic anomalies. The surgical treatment is described and the general features of the cryptophthalmos syndrome and its variants are reviewed. PMID- 2195149 TI - Complete cryptophthalmos: case report with normal flash-VEP and ERG. AB - We report an infant with bilateral complete cryptophthalmos as part of Fraser Syndrome. Clinical examination and recordings of the electroretinogram and flash visual evoked potential showed a functional visual pathway at retinal and post retinal levels. Anatomical considerations and the possible complications of surgery made reconstruction of the lids and palpebral fissures inappropriate. PMID- 2195150 TI - Plaque score changes based primarily on patient performance at specific time intervals. AB - Patient plaque removal is a major component of periodontal therapy and should be continuously monitored during and following treatment. There do not appear to be studies which address plaque score changes achieved primarily by patient performance from the time of initial presentation to, during, and following active therapy. We assessed individual tooth surfaces and segment plaque scores for 24 adult subjects presenting with periodontitis, the majority of which was ADA case types III and IV, at 3 time points (initial presentation, post-initial preparation, and at 3 months following active therapy), using the O'Leary Plaque Index. The assessments describing surfaces and segments were made prior to any professional intervention. Analysis of buccal (B), interproximal (I), and lingual (L) plaque retentive surfaces at t-0 indicated the mean plaque index on B and L surfaces (30.7% and 41.9% respectively) was less than that on I surfaces (79.6%). At t-1 and t-2, the mean plaque index on all three surfaces was significantly (P less than 0.05) less than at t-0. Analysis of plaque indices in each of 6 segments at each time point revealed that plaque scores in all segments, except the mandibular right segment, were analogously reduced from t-0 to t-1 and to t 2. Our results indicate that plaque reduction for all subjects based primarily on patient performance consistently approaches or exceeds 50% on all surfaces and that interproximal surfaces present with and retain more plaque than buccal and lingual surfaces. Furthermore, patient plaque performance achieved at the time of post-initial preparation may be a predictor of the plaque control achievable during therapy based on patient performance. PMID- 2195151 TI - Relationship of gingival bleeding, gingival suppuration, and supragingival plaque to attachment loss. AB - This study evaluated the relationship between the presence of gingival bleeding, gingival suppuration, and supragingival plaque at 3 month appointments to the incidence of probing attachment loss during a 2-year period of maintenance therapy. The data included in this report were taken during the second and third year of maintenance from 75 periodontal patients who had previously received active therapy in an ongoing longitudinal study. The diagnostic sensitivity, specificity, and positive and negative predictive values were calculated for different frequencies of positive responses for each clinical parameter in relation to sites demonstrating greater than or equal to 2 mm probing attachment loss. Gingival bleeding and plaque were not prognosticators and gingival suppuration was a weak prognosticator of attachment loss during a 2 year maintenance period. PMID- 2195152 TI - Clinical efficacy of a dentifrice and oral rinse containing sanguinaria extract and zinc chloride during 6 months of use. AB - The efficacy of combined use of toothpaste and oral rinse containing sanguinaria extract and zinc chloride was compared to placebo products in a 6-month clinical trial. Sixty subjects with moderate levels of plaque and gingivitis were randomly assigned to active and placebo groups. Noninvasive measures of plaque and gingivitis were assessed at baseline and at 2, 6, 8, 14, 20, and 28 weeks. Bleeding on probing was measured at baseline and 6, 14, and 28 weeks. Active group scores were significantly lower (P less than .0001) than placebo scores at each post-baseline time point for all indices, with the exception of plaque at 2 weeks. The 28 week active group scores were 21% lower than the placebo group for plaque, 25% lower for gingivitis, and 43% lower for bleeding on probing. No dental staining or taste alteration was reported in the active group. Three of 30 active group subjects exhibited minor soft tissue irritations that resolved spontaneously without discontinuation of product use. Results indicate that the test products showed good levels of safety and efficacy when administered in a combined use regimen for 6 months. PMID- 2195153 TI - Effect of 6 months use of a dentifrice and oral rinse containing sanguinaria extract and zinc chloride upon the microflora of the dental plaque and oral soft tissues. AB - This study documented the effect upon the oral flora of twice daily brushing with a dentifrice containing 0.075% sanguinaria extract and 2% zinc chloride, followed by use of a mouthrinse containing 0.03% sanguinaria extract and 0.2% zinc chloride. Sixty subjects were randomly assigned to treatment or placebo groups and monitored in a 6-month double-blind clinical trial. Bacteriological samples from the tongue, buccal mucosa, and supra- and subgingival plaque were characterized at 0, 14, and 28 weeks. Microbiological monitoring showed no increases in populations of yeast, staphylococci, coliform organisms, or Pseudomonas. Total Gram-negative counts in supragingival plaque samples decreased 83% in the active group compared to a 232% increase for the control group. Populations of B. intermedius in supragingival plaque were significantly lower in the active group at 3 months and significantly lower counts of Fusobacterium sp. were observed at 3 and 6 months. Results indicate that use of the test products did not promote opportunistic overgrowth of pathogens in the oral flora. Additionally, the alterations in organisms associated with gingivitis may account for reductions in gingivitis seen in the active group. PMID- 2195154 TI - DNA binding factors that bind to the negative regulatory element of the human immunodeficiency virus-1: regulation by nef. AB - The nef gene has been reported to be a silencer of human immunodeficiency virus (HIV) transcription that requires the presence of the negative regulatory element (NRE) located at the 5' end of the HIV long terminal repeat (LTR) to exert its negative effect. We have examined nuclear extracts from human, nontransformed T cells for factors that bind to the NRE of HIV-1 and to determine whether binding of factors to this region can be affected by the nef gene. Using gel retardation and methylation interference assays, we have observed several DNA binding factors that bind to a region between nucleotides -315 and -240 upstream of the cap site, within the NRE segment of the 5' LTR. Furthermore, the precise locations of the binding sites for two of these factors, termed here A1 and R, were determined. Factor A1 appears to belong to a family of cellular activation associated factors (called here A1-A4), but it is distinct in that it is the only DNA binding factor so far observed that appears to be downregulated by the nef gene or its product and that it has been found only in cells undergoing lymphokine-driven cell division. In contrast to the A factors, factor R appears to be associated with cellular quiescence and binds to a nearby but distinct site in the NRE. Experiments in which extracts were mixed before gel retardation suggest that the binding of factors R and A1 are mutually exclusive. Based on these observations we propose a model in which the nef gene aids in the maintenance of HIV latency by downregulating the binding of proliferation associated DNA binding factor, which we have called A1. PMID- 2195155 TI - Bulimia. A review of nutritional and health behaviors. AB - Nurses working with adolescents need an understanding of the clinical syndrome of bulimia in order to identify individuals at risk for this disorder and implement preventive and therapeutic interventions. The epidemiology, early precipitants, physiology, and biochemistry of bulimia nervosa are reviewed. From this integrated framework, implications for treatment are explored with an emphasis on holistic nursing care including health education. PMID- 2195156 TI - Library technology supports resident education. AB - The authors discuss new library services and support for a podiatric residency program. They present information on how to conduct medical literature searches through the use of MEDLINE and CD-ROM MEDLINE. Information on interlibrary loans also is provided. PMID- 2195157 TI - Medical management of symptomatic peripheral vascular disease. AB - As our society becomes older, peripheral vascular disease assumes greater significance. Many patients are not surgical candidates and, therefore, must opt for medical management. The podiatrist often assumes the role of primary health care provider, and a knowledge of the disease process, its consequences, and treatment alternatives becomes paramount. The authors detail the events leading to and the treatment options for symptomatic peripheral vascular disease. PMID- 2195158 TI - Pharmacological characterization of the discriminative stimulus effects of cocaine in rhesus monkeys. AB - Rhesus monkeys (n = 6), trained in a two-lever, food-reinforced paradigm to discriminate cocaine (0.2 or 0.4 mg/kg, i.m.) from saline, received injections of cocaine (0.025-0.40 mg/kg, i.v. or i.m.) or various direct and indirect acting agonists (i.v.). Administration of cocaine resulted in a dose-related increase in the percentage of responses that occurred on the drug-appropriate lever. The indirect dopamine agonists GBR 12909 (0.2-1.6 mg/kg), mazindol (0.025-0.4 mg/kg), nomifensine (0.025-0.2 mg/kg) and bupropion (0.1-1.6 mg/kg) each produced dose related increases in cocaine-appropriate responding, with complete substitution for cocaine achieved at the highest doses of each drug. In contrast, the norepinephrine re-uptake blockers tomoxetine (0.8-6.4 mg/kg) and nisoxetine (0.4 1.6 mg/kg), the serotonin re-uptake blocker fluoxetine (1.6-12.8 mg/kg), the D1 agonist SKF 38393 (3.2-12.8 mg/kg) and the D2 agonist quinpirole (0.05-0.2 mg/kg) failed to engender cocaine-appropriate responding. Administration of the D1 antagonist SCH 23390 (0.05-0.2 mg/kg, i.m.) 20 min before cocaine resulted in a 4 to 8-fold parallel shift to the right in the cocaine dose-response function. Similarly, the D2 antagonist haloperidol (0.003-0.012 mg/kg, i.m.) produced at least a 2-fold shift to the right in the cocaine dose-response function. The results indicate that blockade of dopamine re-uptake is sufficient to mimic the cocaine discriminative stimulus and suggest that stimulation of either D1 or D2 receptors is necessary but not sufficient for the expression of the discriminative stimulus effects of cocaine. PMID- 2195159 TI - Immunohistochemical analysis of bone morphogenetic protein (BMP) in osteosarcoma. AB - The monoclonal antibody against bovine bone morphogenetic protein (bBMP-McAb) was first used for demonstration of bone morphogenetic protein (BMP) in osteosarcoma. The avidin-biotin complex method (ABC) demonstrated that of the 18 osteosarcomas, 15 stained positive, while all 6 fibrosarcomas were negative. The results showed that BMP mainly exists in the tumor cell plasma and some tumor-like bone tissues. Using this staining method, we can not only differentiate osteosarcoma from fibrosarcoma and other non-bone-derived tumors, but also classify osteosarcoma according to the content and distribution of BMP and the patient's clinical situation, thus providing a scientific basis for clinical treatment. PMID- 2195160 TI - Dentin dysplasia type II: absence of type III collagen in dentin. AB - A three-generation family with dentin dysplasia (DD) Type II is presented. Affected family members share common radiologic features with clinically varied expression of tooth discoloration and occlusal wear. Both the primary and the permanent dentition appear to be affected. No generalized connective tissue involvement is found. The mode of inheritance is autosomal dominant. Histologically, the findings are consistent with DD Type II. In indirect immunofluorescence, the irregular radicular dentin of an affected permanent tooth failed to stain with specific antibodies against Type III collagen and the N terminal propeptide of Type III procollagen. PMID- 2195161 TI - Solitary lesion of the mandible resembling a "Stafne cyst" in human archaeologic material from Mokapu, Hawaii. AB - The mandible of a pre-European contact Hawaiian adult displayed a unilateral depression on the inner surface on the third molar region near the angle. The roentgenographic appearance suggested a cystlike lesion lying below the lower border of the mandibular canal and 0.5 cm from the inferior border of the mandible which resembles a "Stafne cyst". PMID- 2195162 TI - Your CE topic (No. 48). Breastfeeding and medications: an update (Part I). PMID- 2195163 TI - Sequence of improvement in agoraphobia with panic attacks. AB - In a multi-center comparison of alprazolam to placebo in the treatment of agoraphobia with panic attacks, the sequence of sustained remission in both treatment groups, was panic attacks before phobias. This may suggest that phobias are secondary to panic attacks in the pathogenesis of the disorder, although other explanations may account for these data and are discussed. PMID- 2195164 TI - Alzheimer cortical neurons containing abundant amyloid mRNA. Relationship to amyloid deposition and senile plaques. AB - Since the detailed molecular events leading to the formation of amyloid containing senile plaques of the Alzheimer's disease (AD) brain are incompletely understood, the present studies were undertaken to address this issue using a combination of molecular and cytochemical approaches. Amyloid precursor protein riboprobes containing the A4 (beta-amyloid) domain were applied to cortex using the in situ hybridization method to examine the distribution of neuronal amyloid mRNA in relation to the laminar pattern of amyloid deposition and the localization of plaques. The derived data indicated that high levels of amyloid mRNA can be synthesized by AD cortical neurons that appeared to be morphologically intact. The distribution of these cells was not coincident with the cortical laminar pattern that is typical of amyloid deposits observed after immunostaining with anti-A4 monoclonal antibodies. Further, there was no obvious relationship between neurons containing abundant amyloid mRNA and the distribution of plaques identified by thioflavin S staining. While the neuronal synthesis of amyloid may be a significant factor at some point during plaque formation, it may not be the exclusive determinant. The possibility is raised that processes affecting secretion, diffusion, and/or transport of amyloid away from neuronal or non-neuronal cells of origin to sites of deposition may be meaningful aspects of the molecular pathology of Alzheimer's disease. PMID- 2195165 TI - An update on the serodiagnosis of canine Lyme borreliosis. AB - The first report of canine Lyme borreliosis was published in 1984, and since that time there have been numerous reports. Clinical manifestations have varied, and serology is often used to make the diagnosis. This review is designed to inform veterinary clinicians about the current serologic tests and their limitations. In endemic areas, the fact that up to 50% of the canine population can be asymptomatic, yet seropositive, suggests that positive antibody titers do not necessarily indicate the presence of disease. Instead, the presence of a positive antibody titer should be considered evidence of exposure to the agent. Many dogs apparently are exposed to the agent of Lyme borreliosis but do not come down with the disease. Immunoblots are not able to distinguish between infection versus exposure. Newer diagnostic tests, such as antigen assays, are being evaluated. However, the fact that spirochetes have been isolated from 8% of asymptomatic dogs living in an endemic area is evidence that these tests will also need to be cautiously interpreted. Our inability to characterize the relationship between clinical signs and serology has hampered our understanding of canine Lyme disease. Presently, the diagnosis should be one of exclusion. A diagnosis of Lyme borreliosis should be considered confirmed only when other diseases are completely ruled out. PMID- 2195166 TI - [Synovial cysts of the hip. Diagnosis by x-ray computed tomography and magnetic resonance imaging]. AB - Report of two cases of synovial cyst of the hip associated with moderate osteoarthritis. Diagnosis was made by computed tomography. Anatomic and radiologic characteristic findings of these synovial cyst are reviewed. PMID- 2195167 TI - [Hepatic infarction of arterial origin. X-ray computed tomographic aspects]. AB - Unlike other major abdominal organs, infarctions affecting the liver is extremely rare. In humans, the rarity of hepatic infarction is explained commonly on the basis of the double blood supply via the hepatic artery and portal vein. The imaging studies and clinical records of seven patients with hepatic infarcts were reviewed. These infarctions were essentially observed during post-operative periods: after aortoceliac graft and after accidental ligation of the hepatic artery (4 cases). The other etiologies included: acute hypovolemic shock in patients with atherosclerosis (2 cases) and finally one case of acute thrombocytosis. Dynamic CT was performed initially in all the cases and during the evolution, demonstrating peripheral low attenuation areas without enhancement. Associated splenic infarcts were present in 4 patients and renal infarcts in two. While the clinical and laboratory findings in hepatic infarction can be completely mimicked by hepatic abscess, CT-guided aspirations were performed in 6 patients demonstrating in only one case the presence of infection. PMID- 2195168 TI - [Diagnosis of venous thromboses of the arm using color Doppler. Study of 4 cases]. PMID- 2195169 TI - [Iatrogenic pseudo-aneurysm of the popliteal artery. Complication of arthroscopic meniscectomy. Apropos of a case]. AB - A case of popliteal artery pseudoaneurysm is reported. It is a rare complication following arthroscopic surgery for meniscal repair. The echographic, computed tomographic and arteriographic findings are described. Both sonography and CT Scan detect the false aneurysm but arteriography is important for determination of the distal vascularization of the leg. PMID- 2195171 TI - Choosing between cancer patients. AB - The leading ethical problem in medical practice for the coming decade is likely to be how to select patients for priority. Criteria for such decision-making in the case of cancer patients are discussed. Clinicians, ethicists and others need to agree guidelines on giving priority to one patient over another when resources are limited, and such criteria need to be approved by society at large. The public must accept that in a non-explicit rationing system, each individual competes with every other. In the case of even more difficult ethical choices, a multidisciplinary national committee is required to advise on decision-making, and its views need to be debated by the general public. PMID- 2195170 TI - Unfinished feticide. AB - A fetus may survive an intentional interference with its intrauterine environment (1) if gestational age is mistaken and the procedure of induced abortion does not kill the fetus, (2) if a change of heart takes place after abortifacient drugs are taken and the abortion does not proceed, and (3) if a high-multiple pregnancy is reduced to a singleton or a twin pregnancy to improve the likelihood that the remaining fetuses will reach viability. In each case, through cause or coincidence, an abnormal baby may be born. The well-intentioned physician, responding to a patient's medical or psychological needs, risks a legal action in negligence or assault brought by a deformed surviving child. This hazard means that medical termination of pregnancy and selective pregnancy reduction put the practising physician at substantial risk in a way not usually associated with induced abortion. PMID- 2195173 TI - Explaining variations in hospital death rates. Randomness, severity of illness, quality of care. AB - We used administrative (Part A Medicare) data to identify a representative sample of 1126 patients with congestive heart failure and 1150 with acute myocardial infarction in hospitals with significant unexpectedly high inpatient, age-sex race-disease-specific death rates ("targeted") vs all other ("untargeted") hospitals in four states. Although death rates in targeted hospitals were 5.0 to 10.9 higher per 100 admissions than in untargeted hospitals, 56% to 82% of the excess could result from purely random variation. Differences in the quality of the process of care (based on a medical record review) could not explain the remaining statistically significant differences in mortality. Comparing targeted hospitals with subsets of untargeted ones, eg, those with lower than expected death rates, did not affect this conclusion. Severity of illness explained up to 2.8 excess deaths per 100 admissions for patients with myocardial infarction. Identifying hospitals that provide poor-quality care based on administrative data and single-year death rates is unlikely; targeting based on time periods greater than 1 year may be better. PMID- 2195172 TI - Prenatal screening in Jewish law. AB - Although prenatal screening is routinely undertaken as part of a woman's antenatal care, the ethics surrounding it are complex. In this paper, the author examines the Jewish position on the permissibility of several tests, including those for Down's syndrome and Tay-Sachs disease, the latter being especially common in the Jewish community. Clearly, the status of the tests depends on whether termination of affected pregnancies is allowed, and contemporary rabbinical authorities are themselves in dispute as to the permissibility of terminating affected pregnancies. The nature of these arguments is examined and the author concludes that there are grounds on which the full range of prenatal screening is permitted in Jewish law. PMID- 2195174 TI - Dr Todd, newly named EVP, will work for friendlier, wiser AMA. PMID- 2195175 TI - Introducing the 1990-1991 AMA-RPS chairperson. PMID- 2195176 TI - Poe: defined as schoolboy, but definition as a novelist is too novel. PMID- 2195178 TI - Long-term follow-up of medically treated patients with coronary artery disease- I. Incidence of major cardiac events and its risk factors in Japanese with coronary artery disease. AB - In the cooperative, multi-center trial, 491 medically treated patients with coronary artery disease were thoroughly assessed and followed for an average of 49 months. The rate of cardiac death and/or non-fatal myocardial infarction was 9.8%; 64% of cardiac events were fatal. Three factors, such as number of diseased coronary arteries, other diseased organs and the cardiothoracic ratio, contributed significantly to the evolution of cardiac events. The outcome of cardiac events in Japan in the period from 1973 to 1985 in patients with coronary artery disease was more favorable than those reported recently in the United States. The results of this study will serve as a control data base for further studies in Japan. PMID- 2195177 TI - Radithor and the era of mild radium therapy. AB - Soon after the discovery of radium, a school of practitioners arose who were interested primarily in the physiological rather than the tumoricidal powers of this new radioactive element. This treatment philosophy was called "mild radium therapy" and involved the oral or parenteral administration of microgram quantities of radium and its daughter isotopes, often as cures for rheumatic diseases, hypertension, and metabolic disorders. Manufacturers of patent medicines responded to this market by producing a variety of over-the-counter radioactive preparations including pills, elixirs, and salves. One such nostrum was Radithor, a popular and expensive mixture of radium 226 and radium 228 in distilled water. Radithor was advertised as an effective treatment for over 150 "endocrinologic" diseases, especially lassitude and sexual impotence. Over 400,000 bottles, each containing over 2 muCi (74 kBq) of radium, were apparently marketed and sold worldwide between 1925 and 1930. The death of the Pittsburgh millionaire sportsman Eben M. Byers, who was an avid Radithor user, by radium poisoning in 1932 brought an end to this era and prompted the development of regulatory controls for all radiopharmaceuticals. PMID- 2195179 TI - [Phase I study of FK 435]. AB - We performed phase I study of FK 435, a new antiestrogen, in 30 patients with advanced breast cancer. Slight to moderate adverse reactions were noted as follows. Single-dose study: anorexia, nausea, lassitude in one patient (80 mg), decreased serum calcium in one (160 mg), redness, tenderness in one, facial flushing, hot flushes, headache in one (320 mg). Repeated-dose study: anorexia, nausea in one patient (40 mg/day), anorexia, diarrhea, increased FSH in one, increased PRL in one (80 mg/day). FK 435 was well tolerated. Tmax was 3-5 hours, T1/2 about 25 hours. Most of FK 435 was excreted into urine as glucuronide. PMID- 2195180 TI - [A case of early carcinoma of the remnant stomach that developed from gastritis cystica polyposa]. AB - A 64-year-old man with an early carcinoma of the remnant stomach that developed from a gastritis cystica polyposa (GCP) is presented, and the morphology and histogenesis of this rare condition are discussed. This patient had a Billroth II reconstructed remnant stomach for 25 years, and was referred to our attention because of cholecystocholedocholithiasis. In screening an upper gastrointestinal barium study and an endoscopy revealed an irregular-shaped, flat, polypoid tumor in a stoma of the posterior wall. The resected polypoid lesion measured 4.5 x 3.0 cm. A histological examination revealed it to be a well differentiated adenocarcinoma of the mucosal layer that had developed from a GCP. PMID- 2195181 TI - [A case of metastatic malignant melanoma of the stomach treated by a surgical operation]. AB - A metastatic malignant melanoma of the stomach is not a disease of rate occurrence, but reports of melanomas that were clinically diagnosed and were treated by a surgical operation are rare. The case presented is a 73-year-old woman, who underwent an excision of a malignant melanoma of the left sole in 1981. Subsequently, she had a subcutaneous metastasis of a melanoma three times and was treated by a resection and immunochemotherapy. In January, 1988, an X-ray examination of stomach revealed a giant elevated lesion, and an endoscopic examination of the stomach revealed a black pigmented tumor with ulceration. A biopsy taken from the tumor confirmed the diagnosis of a malignant melanoma. Thus, she was given a total gastrectomy. Reports in the Japanese literature of metastatic malignant melanomas of the stomach diagnosed while the patient was still living amount to 11 cases. Of this number, 3 patients were given a surgical operation. Further, these 3 patients lived longer than the non-surgically treated cases and had a better quality of remaining life. PMID- 2195182 TI - [Mixed lineage leukemia]. PMID- 2195184 TI - [Evaluation of patients treated by endoscopic injection sclerotherapy by endoscopic ultrasonography--variceal recurrence and rupture]. PMID- 2195183 TI - [A case of autoimmune hemolytic anemia and bullous pemphigoid-like skin lesion combined with idiopathic thrombocytopenic purpura]. AB - A case of autoimmune hemolytic anemia (AIHA) and bullous pemphigoid (BP)-like skin lesion combined with Idiopathic thrombocytopenic purpura (ITP) is reported. A 25-years-old male, who had been diagnosed as ITP and treated at another hospital, was admitted in this hospital recently complaining of disseminated bullous-vesicular eruptions on the whole body and autoimmune hemolytic anemia. Examinations, disclosed that RBC was 364 X 10(4)/microliters, reticulocyte 40, platelet 3000/microliters, direct and indirect Coombs test positive, and platelet Coombs consumption test was positive leading to the diagnosis of AIHA and ITP, known as "Evans syndrome." Vesicular biopsy-findings and immunofluorescence study showed suspicion of BP, but clinical course and blister was not improved though the administration of prednisolone was performed. Reports of cases of BP complicated by Evans syndrome are very few. AIHA, ITP and BP are considered to have autoimmune disorders and their pathogenetic mechanism are discussed. This patient consulted another hospital one year later, when we heard that skin eruptions already had disappeared. PMID- 2195185 TI - [MR three-dimensional Fourier transform imaging at 0.5 T: neurosurgical application]. PMID- 2195186 TI - [HTLV-I associated arthropathy (HAAP)]. PMID- 2195187 TI - [Calpain and calpastatin]. AB - Calpain is a Ca2(+)-dependent cysteine endopeptidase and calpastatin is a calpain specific endogenous inhibitor protein. Both calpain and calpastatin are very widely distributed in various animal tissues and cells. Low (microM) Ca2(+) requiring calpain I and high (mM) Ca2(+)-requiring calpain II are known to exist. Calpain consists of one heavy (80 kDa) and one light (30 kDa) subunit. The heavy subunits of calpains I and II are different genetic products, whereas the light subunits are the same for both calpains I and II. Molecular cloning as well as protein sequencing revealed that the heavy subunit has four domains, while the light subunit has two domains. The carboxyl terminal domain of each subunit is a calmodulin-like domain, whereas the catalytic site is located in domain 2 of the heavy subunit. Calpastatin has four internally repetitive inhibitory domains. A single domain, or even a truncated 27-mer fragment thereof, possesses inhibitory activity against calpains. Calpain shows a rather broad substrate specificity. It can cleave various enzymes, and cytoskeletal, membrane and receptor proteins. Calpain-catalyzed activation of protein kinase C and transglutaminase may represent a few of the physiological functions of calpain, but a great many other functions can be assigned as well to calpain. Immunohistochemical studies revealed very wide but quite diverse distribution of calpains I and II and calpastatin among various tissues and cells. The expression of the genes for calpain and calpastatin is found to be modulated by retrovirus (HTLV-I) infection to T-lymphocytes. The physiological significance of the calpain and calpastatin system is yet to be elucidated, and accumulating information definitely suggested the role of calpain/calpastatin in health and disease. PMID- 2195188 TI - [Coordinate regulation of immune and inflammatory responses by cytokines]. AB - In response to antigenic stimulation, T cells and macrophages secrete a set of glycoproteins termed lymphokines and monokines such as IL-1, IL-2, IL-3, IL-4, IL 5, IL-6, GM-CSF, G-CSF, IFN-alpha, IFN-gamma, TNF-alpha, and lymphotoxin. These glycoproteins mediate immune and inflammatory responses by regulating proliferation, differentiation and maturation of lymphocytes, hemopoietic cells and endothelial cells. Along with factors such as M-CSF, IL-7, LIF, IFN-beta and TGF-beta produced by stromal cells, all these molecules are collectively called cytokines. Most cytokines are pleiotropic and have multiple biological activities. Accordingly, regulatory network is formed between lymphoid cells, hemopoietic cells and endothelial cells. All or a part of this network can be activated in different ways by unique combinations of cytokines. IL-3, IL-4 and IL-5 produced by TH2 cells enhance whereas IFN-gamma produced by TH1 cells suppresses IgE mediated allergic response. Through production of a spectrum of cytokines, T cells and macrophages play a vital role in coordinating the function of different body compartments in immune and inflammatory responses. The activation of cytokines genes in T cells and macrophages is transient. Therefore, an inflammatory response that involves proliferation and maturation of hemopoietic progenitor cells may be restricted to the site of cytokine production. The inducible nature of the hemopoiesis associated with inflammatory response is in contrast to the constitutive, steady state hemopoiesis that occurs in the bone marrow microenvironment in the absence of immunological stimuli. PMID- 2195189 TI - [Impaired glutathione metabolism in hemolytic anemia]. AB - During the delivery of oxygen by erythrocytes, highly reactive oxygen species such as superoxide anion arise. The presence of reactive species damages the cell constituents. Glutathione (GSH) functions to repair cells when they are attacked by oxidative stress. GSH is synthesized in erythrocytes and glutathione disulfide (GSSG) is transported outside the cells to maintain a high GSH/GSSG ratio. The redox cycle of GSH by glutathione reductase and glutathione peroxidase is closely related to G6PD. Hereditary enzyme deficiency related to GSH metabolism, with hemolytic anemia has been reported. G6PD deficiency causes hemolytic anemia due to insufficiency of the redox cycle of GSH. Deficiency of GSH synthesizing enzymes or glutathione reductase also causes hemolysis. Pyrimidine 5' nucleotidase deficiency causes hemolytic anemia even when there is a high concentration of GSH. Accumulation of nucleotides in red cells causes inhibition of G6PD activity. PMID- 2195190 TI - [Erythrocyte membrane and hereditary spherocytosis]. AB - Hereditary spherocytosis (HS) is the most common hemolytic anemia caused by intrinsic defects of the erythrocyte membrane. Recent investigations have been directed toward the cytoskeleton of affected cells, and in some patients, the following several molecular lesions have been identified: (1) an abnormal spectrin incapable of binding to band 4.1 in dominantly inherited HS, (2) a deficiency of spectrin in severe, recessively inherited HS, (3) a deficiency of ankyrin and spectrin in severe, atypical HS, and (4) complete or partial defect of band 4.2 in some Japanese cases with HS. However, in the majority of patients with HS, the molecular lesion still remains unclear. We determined the transport rate of phosphoenolpyruvate (PEP) in HS erythrocytes, which was found to be specifically lower by almost half of the rate in erythrocytes from normal subjects or patients with other anemias. Since PEP is transported via band 3, the phenomenon may be a reflection of either structural abnormality of band 3 or dysfunction of band 3 caused by other primary lesions. Further investigations is needed to elucidate the underlying molecular defects in majority of patients with HS. PMID- 2195191 TI - [Quantitative analysis of cytokines and its problems]. AB - Current features of interleukins and cytokines are summarized with emphasis laid on their biological significance. Based on the biological activities of these cytokines, a variety of bioassays for the detection and quantitation methods have been developed. Simple and useful bioassays using cytokine-dependent cell lines are introduced. In particular, bioassays on IL 1, IL 2, IL 4, IL 5 and IL 6 are illustrated in detail. Recent developments on the various immunoassays (ELISA and RIA), which are more specific to each cytokine, are reported. In addition, the problems and limitations of these assay methods are pointed out. PMID- 2195192 TI - [Histopathology of malignant lymphomas]. AB - Histopathological features of malignant lymphomas were described and discussed. For the standard classification of malignant lymphomas, the Rye classification for Hodgkin's disease and the International Working Formulation for the non Hodgkin's lymphoma were recommended. Recent advances in immunology make immunophenotyping of lymphoma cells possible. The usefulness of immunophenotyping in routine paraffin sections was suggested. Some problems of the Working Formulation in classifying T-cell lymphomas were also discussed. A significant difference in the 5-year survival between the different histological grades of Working Formulation and between T and B phenotypes was found in a survey using 604 non-Hodgkin's lymphoma cases of our own. It is concluded that precise histological typing and immunophenotyping of lymphomas are mandatory in the diagnosis, treatment and prediction of the prognosis of patients with malignant lymphomas. PMID- 2195193 TI - [Radiographic staging procedures and radiotherapy of malignant lymphoma]. AB - Radiographic studies play an important role in the clinical staging of malignant lymphoma (ML). Conventional procedures are plain chest X-ray, lymphangiography, gastrointestinal series, and 67Ga scintigraphy. Gastro-intestinal series is essential in non-Hodgkin's lymphoma (NHL) of Waldeyer's ring and thyroid. 67Ga scintigraphy is a non-invasive procedure useful in the screening of ML. Recently marked improvements have been made in the diagnostic modalities. CT scan and NMR have made it very easy to diagnose ML of the central nervous system and detect the extension of tumors at all sites. In some cases with Hodgkin's disease (HD), staging laparotomy is necessary, but not in cases with NHL. If tumors are localized, subtotal or total nodal irradiation is performed for patients with HD, and generous involved field is employed for NHL with or without combined chemotherapy at our department. Good local control is obtained except for NHL of the central nervous system at a total dose of 40-50 Gy. NHL is prone to relapse outside the radiation field. Therefore we consider that combined chemotherapy is indicated for NHL such as T-cell lymphomas, those with high grade histology classified according to the Working Formulation, and with involvement of lymph nodes larger than 6 cm in diameter. PMID- 2195194 TI - [Recent advances in diagnosis and treatment of colorectal cancer]. AB - There are several methods to detect colon cancer in asymptomatic people; questionnaire, fecal occult blood test, barium enema study, endoscopy and so on. In our study, patients with colon cancer were easily differentiated from normal subjects by analyses of questionnaire responses, but early cancer was not differentiated well. Immunological fecal occult blood test was enough to screen out cancer correctly. Contrast barium enema and colonoscopy have been necessary to diagnose colon cancer and other lesions. Fine lesions 2-3 mm in diameter can be diagnosed by the skillful double contrast method and more diminutive lesions by the dyeing and magnifying colonoscopy. Endoscopic ultrasonography (EUS) can provide useful information for the diagnosis of cancer. At present, EUS provides information concerning the extension of colorectal cancer with considerable reliability. The video endoscope system with the CCD chip is electronically transmitted to a video processor for display by a television monitor. Application of a computer at the level of image processing is expected to open a new field in endoscopic diagnosis. PMID- 2195195 TI - [Large bowel cancer: prognostic factors, surgical treatments and their results]. AB - Although the classification proposed by Dukes has been repeatedly modified, causing unnecessary confusion, his original concept remains unrefuted; cancer penetration through the bowel wall and lymph node metastasis are two major prognostic factors, of which nodal metastasis represents a more advanced stage. However, the results of our exhaustive computer analyses did not support this concept, and better classifications may be developed using our computer algorithm, enabling us to refine the indication for extensive surgery or limited resection. There are two trends of surgical treatment in Japan. One is an attempt to extend the area of resection including the paraaortic and parailiac nodes, and also iliac vessels. Patients treated by this method show a higher survival rate if compared with historical controls in Japan. However, extensive surgery of the rectum is associated with poor quality of life with bladder and anal dysfunctions as well as sexual impotence. The other trend is to limit the extent of resection and minimize the functional defect. The organs thus saved include the sphincter and autonomic nerves. The results are almost comparable with those of more radical surgery. With aggressive re-resection of recurrent tumors in the liver, lungs, lymph nodes and local areas, the number of long-term survivors is now increasing who would otherwise have died. PMID- 2195196 TI - [Mechanism mediating HIV replication in infected individuals]. AB - A long asymptomatic period is one of the characteristics of human immunodeficiency virus (HIV). How actively HIV replicates in vivo and what controls viral replication during this period remains to be clarified. Proviral DNA integrated into the cellular DNA of peripheral blood lymphocytes (PBL) is not completely silent, but the viral antigens in PBL are extremely low. Several mechanisms have been proposed to explain the low levels of viral replication: i) the regulatory genes encoded in HIV might control the expression of viral DNA, ii) the majority of the proviruses might be defective, iii) host immune systems such as T cell-mediated HIV-specific cytotoxicity and antibody-dependent cellular cytotoxicity might eliminate infected cells, and iv) CD8+ lymphocytes might suppress spontaneous viral replication in PBL. PMID- 2195197 TI - [Clinical manifestations of acquired immunodeficiency syndrome (AIDS), with reference to cases reported in Japan and our observations on two of HIV-infected homosexuals]. AB - This article provides an overview of the clinical presentations of human immunodeficiency virus (HIV) infection, including some of the early and less severe diseases, such as acute HIV infection, persistent generalized lymphadenopathy (PGL) and acquired immunodeficiency syndrome (AIDS) related complex (ARC), and full-blown AIDS. The salient features of 24 cases of AIDS reported in Japan were summarized. There was no difference in clinical features between hemophiliacs (16 cases) and homosexual males (8 cases), except for a preponderance of cases of cytomegalovirus infection in the latter group. The new prognostic staging system, based on physiologic deficits, for AIDS was applicable to Japanese patients with AIDS. In addition, a three-year follow-up study on two of HIV-infected homosexuals was presented. PMID- 2195198 TI - [Diagnosis of HIV by clinical pathological methods]. AB - HIV (human immunodeficiency virus)-I infection can be detected by the presence of HIV antigen, antibody to HIV, or gene of HIV itself in patient's blood. There are a considerable number of such antibody detecting methods (first generation) commercially available, but even the first was introduced in only mid-1985. These tests detect antibody in more than 90% of patients with confirmed AIDS. Recently, new antibody detecting methods (second generation) was produced using a single antigen (e.g. p 24, gp 41) of HIV-I by recombinant DNA or synthetic peptide. Furthermore, detection methods for DNA or RNA of HIV were developed and these methods are introduced in clinical use in near future. PMID- 2195199 TI - [Thyroid peroxidase]. AB - Thyroid Peroxidase (TPO) is a key enzyme in the synthesis of thyroid hormone and is a major thyroid microsomal antigen corresponding to anti-microsomal autoantibodies in thyroid autoimmune diseases. We studied the autoantigenicity, thyroiditogenicity and gene structure of TPO. In micro-ELISA using human TPO as a target, all sera from patients with anti-microsomal antibodies contained IgG class of antibodies to TPO and some sera had IgM class of antibodies. The competitive inhibition test revealed that TPO is the major thyroid microsomal antigen. Experimental murine thyroiditis was successfully induced by the immunization of porcine TPO. Susceptibility of thyroiditis in each strain was very different from that of thyroiditis induced by thyroglobulin. T-cell line specific for porcine TPO could mediate thyroid lesions. Two kinds of full length cDNAs to human TPO were isolated from cDNA library which was constructed from mRNA purified from thyroid with Graves' disease. The longer one consisted of 3,048 nucleotides and its open-reading-frame was likely to encode 933 amino acids. The shorter one lacked 171 nucleotides at the middle portion of the longer one. The structure-gene for human TPO was located on 2q and consisted of 17 exons. One hundred and seventy-one nucleotides deleted in the shorter cDNA exactly corresponded to the 10th exon. PMID- 2195200 TI - [Management and treatment of acute myocardial ischemia in diabetic patients]. PMID- 2195201 TI - [Management of tissue necrosis of the foot in diabetic patients]. PMID- 2195202 TI - [Respiratory, circulatory and metabolic adaptation to prolonged exercise]. PMID- 2195203 TI - [Regulation of glucose metabolism during exercise and after exercise in normal and diabetic subjects]. PMID- 2195204 TI - [Eating before, during and after physical exercise in normal and diabetic subjects]. PMID- 2195205 TI - [Insulin and atherogenesis]. PMID- 2195206 TI - [Natural history of insulin resistance and hyperinsulinism in non-insulin dependent diabetic patients]. PMID- 2195207 TI - [Hyperinsulinemia and/or hyperglycemia in insulin-treated diabetic patients? Choice of relative risks]. PMID- 2195208 TI - [Non-insulin-dependent diabetes mellitus: what we have learnt from studies carried out among Pima Indians]. PMID- 2195209 TI - [Role of and current technical possibilities for intracorporeal determination of blood glucose in the treatment of insulin-dependent diabetes mellitus]. PMID- 2195210 TI - [Hormone replacement therapy of menopause in diabetic women: uncertainties and currently offered choices]. PMID- 2195211 TI - [Brown adipose tissue: physiologic effector of thermogenesis]. PMID- 2195212 TI - [1990 Apollinaire Bouchardat Prize. Immunology of insulin-dependent diabetes mellitus: in vitro and in vivo study models in animals]. PMID- 2195213 TI - [1990 Maurice Derot Prize. Young diabetic patients in society]. PMID- 2195214 TI - [Identification and prevention of vascular risk. Significance of metformin]. PMID- 2195215 TI - [Macroangiopathy and type 2 diabetes mellitus: significance of Diamicron]. PMID- 2195216 TI - [Genetics and energy metabolism in humans]. PMID- 2195217 TI - [Sugar diabetes mellitus and physical exercise]. PMID- 2195218 TI - [Energy expenditure in obese patients]. PMID- 2195219 TI - [Nutrient balance regulation in subjects with normal weight and in obese patients]. PMID- 2195220 TI - [Management and treatment of hyperosmolar coma]. PMID- 2195221 TI - [Energy expenditure items]. PMID- 2195222 TI - [Craniotabes, craniomalacia (Wieland) and active ricketts in infants]. AB - The symptom "craniotabes" means rickets only in few cases. Determinations of calcium, alkaline phosphatase, phosphorus and if possible 25-OH-vitamin D are necessary for confirmation of the rickets-diagnosis. As denotation for the not rickets-caused forms of craniotabes the definition positioning caused craniotabes is suggested. PMID- 2195223 TI - [The mechanism of the formation of pathological scars]. PMID- 2195224 TI - [Development of genetic research in ophthalmology with special reference to Switzerland]. AB - The relationship between ophthalmology and genetics has always been a very active one, and existed even before Mendel's laws of inheritance were known. The pedigree method in particular yielded satisfactory results even to the first researchers. Later, Helmholtz's invention of the ophthalmoscope (in 1851) and the rediscovery of Mendel's laws of heredity (in 1900) made major contributions to the progress of human genetics in ophthalmology. Credit is due to J. F. Horner of Zurich (1831-1886) for having first established the X-chromosomal inheritance of colorblindness. Subsequently, the development of genetic research was advanced in particular by Alfred Vogt, Professor of Ophthalmology in Zurich (1879-1943) and Adolf Franceschetti in Geneva (1896-1968) and their co-workers. We are indebted to Vogt for the first description of albinismus solum bulbi. Credit is also due to him for having made early diagnosis of myotonic dystrophy (Steinert) possible, a major discovery for genetic counseling. He was the first to detect, by slit lamp examination, characteristic lens changes in the form of whitish, red, and green opacities in the anterior and posterior subcapsular regions. Franceschetti's achievements include the description of several clinical syndromes, of which mandibulofacial dysostosis has become well known. Among the hereditary retinal dystrophies, he described fundus flavimaculatus (yellowish lesions disseminated in the deeper layers of the posterior pole) as a new entity, attributed to degeneration of the pigment epithelium. In addition to more than 500 articles, he was also co-author, with J. Francois and J. Babel, of a monumental handbook in two volumes titled Heredodegenerescences chorioretiniennes (of which an English translation appeared in 1974).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2195225 TI - [Astigmatism following cataract surgery: comparison following wound closure with nylon suture and Mersilene]. AB - Mersilene (polyester fiber) is stronger and less elastic than nylon suture material. In contrast to nylon, Mersilene does not appear to be susceptible to biodegradation in the long term. After a follow-up period of 6 months, the regression of surgically induced astigmatism following extracapsular cataract extraction and lens implantation with a conventional 150 degree corneoscleral incision was in the same range with nylon monofilament 10-0 and Mersilene 10-0. With nylon single sutures (14 patients) there was a reduction from 3.5 and with Mersilene (12 patients) from 3.9 to 0.9 diopters. PMID- 2195226 TI - [Small incision cataract surgery: changes in postoperative astigmatism]. AB - The course of postoperative astigmatism was studied in 2 groups of patients following phacoemulsification and IOL implantation. In the first group a soft posterior chamber lens (IOGEL, Alcon) was introduced through a 6.5 mm scleral pocket incision. In group 2 the IOGEL lens was implanted through a 3.5 mm incision using a new instrument. The patients in group 2 had lower postoperative astigmatism and achieved stable refraction significantly earlier than group 1 patients. Three weeks postoperatively changes in refraction were seen in only a few cases. The small-incision technique significantly accelerates the visual rehabilitation of cataract patients. PMID- 2195227 TI - [A clinical trial with a new silicone implant by Silikon Optik]. AB - A new silicone IOL is described which was implanted in 57 eyes, in 50 cases following phacoemulsification through a 4.2-4.8 mm incision. The principal advantages of this IOL are (a) faster visual rehabilitation, because postoperative astigmatism is reduced and more stable, and (b) less glare and color alteration than after implantation of PMMA lenses. These optical advantages may be due to the non-occurrence of optic decentration, the absence of positioning holes, the biconvex optic, the fact that the surface is less reflective than that of PMMA, and the Tyndall effect of the lens material. The only disadvantage of this lens as compared to PMMA lenses is that the YAG laser is more likely to produce pitting or cracks during capsulotomy. PMID- 2195228 TI - [Immunohistochemical differentiation of periretinal membranes]. AB - The etiology of periretinal membranes, a complication of various ocular diseases, trauma, and ocular surgery, is still unknown. In the study reported here, 134 surgically removed periretinal membranes were semiquantitatively analyzed by immunohistochemical and morphological method (antigens S 100, GFAP, leukocyte antigens, factor 8; fibrosis). It was found that the cell population of the membranes varied both morphologically and immunohistochemically according to the disease. However, the RPE cell count did not correlate with the number of retinal tears recorded in the patients' histories. PMID- 2195229 TI - [Ptosis surgery: shortening the levator aponeurosis of Muller's muscle and the tarsus using an anterior approach]. AB - In cases of moderate congenital ptosis, better lid elevation can be achieved by resection of the levator muscle through a skin incision, combined with tarsectomy and shortening of the superior tarsal muscle. The function of the levator muscle can thus be fully exploited. PMID- 2195230 TI - [Surgery of the eyelid edge--references for general practice]. AB - a) Punctum plasty (eversion of the lacrimal point): This simple method results in a permanently enlarged punctum. A 4-0 silk suture is passed through the vertical part of the canaliculus and the conjunctiva, drawing them together very tightly. The thread falls out after 4-6 weeks. b) Management of trichiasis: Electrolysis of misdirected lashes leads to contraction and renewed misdirection. This disadvantage is avoided by excising the lashes with a 1 mm trephine. The trephine must follow the direction of the lash exactly, so that a complete cylinder including the hair and root can be removed. The resulting small defect heals quickly without contraction. PMID- 2195231 TI - [Bilateral angle block glaucoma in spontaneous choroid detachment]. AB - A 66 years old patient suffered from a bilateral acute glaucoma attack, provoked by a spontaneous bilateral choroidal detachment. After Nd-YAG iridotomies and local steroid treatment the detachments resumed, the anterior chamber angles deepened, and the intraocular pressures returned to normal. PMID- 2195233 TI - [Effect of relaxation on the perceptive-motor work capacity of humans]. PMID- 2195232 TI - [Ultrasonic diagnosis of the changes in human tibia during 370-day antiorthostatic hypokinesia]. AB - Nine volunteers, aged 27 to 41 years, were exposed to 370-day head-down tilting during which their tibia bones were examined by measuring acoustic parameters with the aid of exponential point concentrators located at a 15 mm distance. Although the bone acoustic profile showed individual variations, the decrease of the average ultrasound velocity in the middle part and the gradient of the ultrasound velocity in the distal part of the diaphysis occurred primarily in the first half of the bed rest study, thus reflecting changes in bone adaptation to mechanical loads (redistribution of elastic properties along the bone). The acoustic parameters measured noticeably responded to countermeasures used (or not used) during bed rest (exercise) and therefore can help obtain better prognostic information about bone is compared to the data accumulated by means of monophoton absorptiometry (mineral density measurement). This method can be well used for examining long bones in extended space flight. PMID- 2195234 TI - Cystitis, urolithiasis and cystic calculi in ageing guineapigs. AB - Nineteen cases of cystitis were diagnosed at necropsy and/or by histology in a group of 170 (96 females, 74 males) guineapigs (11.2%). Seventeen of the 19 cases (89.4%) were females. The mean age of guineapigs with cystitis was 34.7 months, which was higher than the mean age of 24 months of the 170 members of the study group. In addition, 6 cases of urolithiasis and cystic calculi in 5 females and one male were also found in the 170 guineapigs (3.5%). The mean age of the 6 cases was 30 months, which was also higher than the mean age of the 170 animals. The study suggests that aged female guineapigs were much more predisposed to cystitis and urolithiasis or cystic calculi than male and young guineapigs. The cause may be related to infection with Escherichia coli and Staphylococcus sp, cystic calculi, diabetes mellitus and female guineapig urogenital anatomy and function. PMID- 2195235 TI - In memory of Prof. Venerando. PMID- 2195236 TI - Acute effects of muscle fatigue and recovery on force production and relaxation in endurance, power and strength athletes. AB - Acute effects of fatigue produced by a maintained 60% isometric loading on force production and relaxation characteristics of the leg extensor muscles were studied in male endurance (n = 9), power (n = 6) and strength athletes (n = 9). The initial non-fatigued isometric force-time curves differed considerably (p less than 0.05-0.001) between the groups so that the times of force production were the shortest and correspondingly the maximal rate of force production the greatest in the power athletes but the longest and the smallest in the endurance athletes. The endurance time of 70.7 +/- 32.9 s at the 60% fatiguing loading was in the endurance athletes longer (p less than 0.01) than in the power (30.6 +/- 7.1 s) and strength groups (31.7 +/- 5.5 s). The present fatiguing loading resulted in all athlete groups in significant (p less than 0.05-0.001) worsening in maximal force, in the times of force production and in the maximal rates of force production and relaxation. However, this worsening in the endurance athletes in maximal force (to 92.9 +/- 7.1%) as well as in the maximal rates of force production (to 79.2 +/- 20.8%) and relaxation (to 73.1 +/- 29.2%) were significantly (p less than 0.05-0.01) smaller than the corresponding decreases in the power athletes (to 64.3 +/- 8.0%, 74.8 +/- 7.4% and to 40.9 +/- 12%, respectively) and in the strength athletes (to 65.7 +/- 7.0%, 56.7 +/- 16.0% and to 34.8 +/- 6.7%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2195237 TI - The role of endocrine therapy in primary breast cancer. AB - A recent overview of the results of all trials of adjuvant chemotherapy suggests a clinically and statistically significant advantage for premenopausal women with positive axillary nodes. The results of the same approach for all other women with early breast cancer are very disappointing. These data suggest that contrary to the original hypothetical model, adjuvant chemotherapy is exerting its effect indirectly via chemical castration. In contrast, the results of trials of adjuvant tamoxifen have been more promising and, again, in contrast to the original premises, it would appear that a modest improvement in survival and delay in recurrence can be achieved amongst all groups of women independent of age, nodal status and oestrogen receptor content of the primary tumour. In order to explain these counter-intuitive observations, it is necessary to elaborate an alternative biological model. This paper describes the current thinking on the mode of action of the "anti-oestrogens" and the possible role of inhibitory growth factors activated indirectly by anti-oestrogens. Future trials of adjuvant systemic therapy for early breast cancer should include studies on the duration of tamoxifen, comparing 2 yr with longer, and a comparison of tamoxifen alone with polychemotherapy for premenopausal node positive patients. PMID- 2195238 TI - Pericardial closure after cardiac operations. An animal study to assess currently available materials with particular reference to their suitability for use after coronary artery bypass grafting. AB - An experimental study to assess the performance of currently available pericardial substitutes is described with particular reference to their use after coronary artery bypass grafting. Seventy-two ewes, (six groups of 12 animals) had a 7 x 5 cm portion of the pericardium excised. Each group had either the defect left open, primarily resutured, replaced with coarse Dexon No. 2 mesh (American Cyanamid Co., Danbury, Conn.), replaced with fine Dexon No. 8 mesh, replaced with glutaraldehyde-preserved bovine pericardium, or replaced with polytetrafluoroethylene 0.1 mm surgical membrane. Six animals from each group were assessed at 3 months and the remaining six animals were assessed at 6 months. The open-defect and resutured groups served as control animals. None of the substitutes proved superior to the open-defect group in the prevention of chest wall/lung-to-pericardium adhesions at either 3 or 6 months. The limitations of the animal model in assessing this aspect of substitute performance are discussed. Whereas the bovine pericardium, polytetrafluorethylene, and Dexon No. 8 mesh groups were superior to the resutured group in the prevention of pericardium-to-epithelium adhesions in the area of the patch, this advantage was lost at 6 months when resuturing proved as effective as polytetrafluoroethylene and bovine pericardium. In all groups there was little tendency to produce generalized pericardial adhesions. At 3 months Dexon No. 8 mesh and bovine pericardium produced the least amount of significant epicardial reaction. In two animals in the 3-month polytetrafluoroethylene group and in one animal in the 6 month polytetrafluoroethylene group, a "fibrous peel" was encountered on the inner surface of the patch, which had also become adherent to the epicardium and had obscured the underlying anatomy. At 6 months the open-defect, resutured, and bovine pericardium groups had produced no significant epicardial reaction. In one animal at 6 months the bovine pericardium had become markedly thickened and degenerative. We do not recommend routine closure of the pericardium after coronary artery operations with any of the substitutes investigated in our study. PMID- 2195239 TI - The BN acute myelocytic leukemia (BNML) (a rat model for studying human acute myelocytic leukemia (AML)). AB - Even if animal models have many properties in common with the human disease, as is the case for the BNML and human AML, they have their limitations with respect to the extrapolation to the clinical situation. This also holds for the BNML; thus, conclusions should only be drawn with great caution. Nevertheless, the studies in the BNML model have added considerably to the understanding of various processes that occur during the development of leukemia, e.g., the interaction of leukemic cells and normal hemopoietic stem cells in relation to the microenvironment. The methodology developed in the BNML model allows the quantification of the relative effectiveness of any given treatment with regard to the antileukemic activity compared with the toxicity for normal host tissues. Furthermore, the cell kinetic studies performed in the BNML as a consequence of timed sequential chemotherapy has been helpful in designing an approach to take advantage of this phenomenon in the treatment of acute leukemia. The comparison of the various treatment modalities, employed for the conditioning prior to bone marrow transplantation, made it possible to determine the relative effectiveness of the various approaches. The fractionation of total body irradiation for conditioning purposes was supposed to have a negligible effect with regard to a reduced antileukemic effect. Detailed studies that were conducted in the BNML model did not confirm this hypothesis indicating that (hyper-)fraction of TBI results in a reduced antileukemic effect. The in vitro purging studies in the BNML aimed at the elimination of residual leukemic cells in autologous bone marrow transplantation contributed to the introduction of this method in clinical practice. However, extended studies in the BNML model also indicated that the contribution of the residual leukemia cell in the patient contributed to a much greater extend to the recurrence of leukemia then did the residual cells in the autologous marrow graft. A major contribution of the BNML was achieved in the study of the area of so-called "minimal residual disease" (MRD). A number of so far unknown aspects of relapsing leukemia could be identified and studied. A new concept of discriminating locally relapsing leukemia and a delayed occurrence of generalized spreading of leukemia formed the basis for the explanation of the observed heterogeneity in the distribution of leukemic cells during the remission and the subsequent relapse phase. In conclusion, it is obvious that proper comparison of the human disease as well as the counterpart in the animal model requires a detailed knowledge of both.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2195240 TI - 125th anniversary of the birth of Dr. Charles H. Mayo. PMID- 2195241 TI - Results of a 6-month survey of stool cultures for Escherichia coli O157:H7. AB - Escherichia coli O157:H7 is a recently recognized enteric pathogen that causes acute hemorrhagic colitis. Although the infection is usually self-limited, it may be complicated by hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. At our institution, stool specimens are now routinely cultured for this organism. To determine the prevalence of E. coli O157:H7-associated diarrhea in our patient population, we surveyed all submitted stool cultures for 6 months for this organism. Specimens were screened for non-sorbitol fermenting E. coli and confirmed by slide-agglutination and immobilization testing. Of 2,164 specimens, 10 yielded E. coli O157:H7. It was the fourth most common bacterial stool pathogen found. Bloody diarrhea and abdominal pain were the most common symptoms of the infected patients. E. coli O157:H7 causes sporadic infections in our patient population and should be considered in the differential diagnosis of acute hemorrhagic colitis. PMID- 2195243 TI - Erwin Schrodinger--physicist. PMID- 2195242 TI - Familial testicular cancer: report of six cases and review of the literature. AB - The cause of testicular cancer, like most other cancers, is unknown. Certain risk factors such as cryptorchidism, carcinoma in situ, and a preceding contralateral testicular germ cell neoplasm are known to predispose a person to the subsequent development of a testicular malignant lesion. Familial testicular cancer has been debated as a potential and possibly independent risk factor. Evidence in favor of such a hypothesis, based on various genetic studies reported during the past few decades, is reviewed. We add to the existing literature our experience with six cases of familial testicular cancer encountered during a 10-year period, consisting of four father-and-son pairs, one pair of nontwin brothers, and a 23 year-old man who had a maternal uncle with a history of testicular cancer. PMID- 2195244 TI - Nocardia asteroides pericarditis: report of a case and review of the literature. AB - In this report, we describe a patient who had purulent Nocardia asteroides pericarditis. In addition, we identified 13 previously suspected and reported cases of Nocardia pericarditis, but only 5 of these studies reported isolation of Nocardia from cultures of pericardial fluid or pericardium. Analysis of the clinical course of these five patients and our patient revealed the importance of long-term sulfonamide antibiotic therapy in combination with surgical pericardial drainage procedures. In our review, only patients who received antibiotics and underwent pericardiectomy survived. Our case substantiates the excellent penetration of sulfisoxazole into the pericardial fluid, even with oral administration of the drug, and provides evidence in support of aggressive management of Nocardia pericarditis. PMID- 2195245 TI - Pulmonary fibrosis as an unusual clinical manifestation of a pulmonary-renal vasculitis in elderly patients. AB - Between 1978 and 1988, three patients at our institution had an initial diagnosis of idiopathic pulmonary fibrosis but later were correctly diagnosed as having pulmonary-renal syndrome and microscopic polyarteritis. These cases involved elderly patients with progressive dyspnea and nonproductive cough, bilateral dry crackling rales, bilateral interstitial infiltrates evident on a chest roentgenogram, and restrictive findings on pulmonary function testing. In two patients, lung biopsy specimens were obtained, and an initial diagnosis of nonspecific pulmonary fibrosis was made. All three patients eventually had microhematuria and renal insufficiency. A revised diagnosis of small-vessel pulmonary-renal vasculitis was based on the demonstration of segmental necrotizing glomerulonephritis in renal biopsy specimens in two patients, thrombotic microangiopathy consistent with healed vasculitis on postmortem examination of the kidney in one patient, and subsequent detection of small vessel vasculitis on review of the two lung biopsy specimens. Anti-neutrophil cytoplasmic antibodies with perinuclear staining on indirect immunofluorescence microscopy were positive in the two patients in whom determinations were performed. The clinical manifestations of vasculitis were notably scarce--no involvement of the skin, nervous system, or gastrointestinal tract; no episodes of fever; and minimal or absent musculoskeletal symptoms. These cases illustrate the importance of a high index of suspicion for the diagnosis of systemic vasculitis in elderly patients and the need to consider a vasculitis in the differential diagnosis of idiopathic pulmonary fibrosis, especially if an active urinary sediment is present. PMID- 2195246 TI - Mayo sleep disorders uptake. PMID- 2195247 TI - Sleep disorders in psychiatric practice. AB - Sleep disorders medicine and psychiatry interface in numerous ways. Most psychiatric patients have a complaint about sleep, and regardless of the theoretical orientation of a psychiatrist, understanding of a patient's sleep function is an important part of assessment. The success or failure of treatment will be strongly influenced by the effect of that treatment on the patient's sleep disorder. The psychiatrist can provide expertise in treating patients with primary sleep disorders, offering pharmacologic consultations, and recommending psychotherapy or behavioral management. Conversely, a knowledge of primary sleep disorders should make the psychiatrist a more effective practitioner. PMID- 2195248 TI - Insomnia. AB - Because sleep needs vary from person to person, insomnia is defined as the chronic inability to obtain the amount of sleep needed for optimal functioning and well-being. Insomnia, which is a symptom rather than a disease, can be classified into three main etiologic groups: insomnias related to other mental disorders (for example, depression and anxiety), insomnias related to known organic factors (for example, sleep apnea and "nonrestorative" sleep), and primary insomnia (for example, learned psychophysiologic insomnias and insomnia complaints without objective findings). The treatment for insomnia often involves a combination of pharmacotherapy, behavioral and short-term psychotherapy, and sleep hygiene guidelines. Sleep disorders centers can provide specialized knowledge and techniques for patients with severe chronic insomnia. PMID- 2195249 TI - Hemorrhagic colitis and Escherichia coli O157:H7--identifying a messenger while pursuing the message. PMID- 2195250 TI - The tertiary diagnosis of rare hemoglobin variants. PMID- 2195251 TI - Protein profiles of microsections of the fetal and adult human lens during development and ageing. AB - The water-soluble proteins of the human fetal lens (175- and 285-day-old) contain HM-, pre-alpha-, alpha-, beta- and gamma-crystallins. Using the frozen-sectioning technique, it can be demonstrated that the fetal lens does not have an homogeneous distribution of crystallins, but there are gradual differences between the cortices and the nucleus. The frozen-sectioning technique shows for the adult lens significantly increasing amounts of beta-crystallins of pI 4.95 5.55, especially at the posterior supra-nuclear layer, increasing amounts of HM crystallins and decreasing amounts of beta-crystallins of pI 5.80-7.05 in the nucleus. This microsectioning technique was correlated with Scheimpflug photographs of the fetal and adult lens. In the fetal lens, the anterior capsule and 2 peaks in the anterior and posterior supranuclear layers could be visualized after densitometry. In the adult lens 5 layers could be demonstrated, e.g. the anterior capsule, the anterior supranuclear layer, the nucleus, the posterior supranuclear layer and the anterior capsule. PMID- 2195252 TI - Biased selection under an experimental enrollment and marketing Medicare HMO broker. AB - All studies conducted to date suggest that nearly all Medicare HMOs have experienced favorable risk selection in their Medicare HMO enrollments. While there is little definitive empiric knowledge about the extent to which Medicare HMOs can and do encourage favorable selection through marketing and enrollment activities, it has been speculated that centralizing all such functions through an independent broker could reduce enrollment selection bias. In 1985, the Health Care Financing Administration initiated a three-year demonstration of a HMO broker model in Portland, Oregon, known as Health Choice, Incorporated (HCI). This study reports empiric findings that provide no evidence to support claims of the efficacy of an enrollment brokerage function in reducing Medicare HMO enrollment selection bias. PMID- 2195253 TI - [Amyloidosis associated with dialysis]. PMID- 2195254 TI - [Difficulties in the prevention of malaria in Spain continue]. PMID- 2195256 TI - Medical and surgical complications of renal transplantation: diagnosis and management. AB - Renal transplantation is a common modality of therapy in end-stage renal failure, but it has the potential of developing many complications, both surgical and medical in nature. In transplantation surgery, more than in any other type of surgery, prevention of these complications is essential. This includes attention to many details, including optimum organ salvage, preservation, implantation, and postoperative care. Although infection has decreased in frequency and severity with the advent of antiviral and antibacterial agents, prevention, early diagnosis, and suitable treatment with appropriate antibiotic(s) will be necessary to obtain desirable results and to reduce morbidity and mortality. It should be stressed that although careful attention to the patients and adjustment of the immunosuppressive regimen may mitigate much of the gastrointestinal, hematologic, and osteogenic complications, high incidence of cancer of the skin and mucous membrane continues. PMID- 2195255 TI - On the natural tendency to progressive loss of remaining kidney function in patients with impaired renal function. AB - Patients who lose more than 50% of their functioning renal mass are at risk to develop progressive deterioration of their remaining kidney function, even though the process that caused the original loss of kidney function may no longer be present. The glomerular capillary hyperperfusion, hypertension, and hyperfiltration that occur in the surviving nephrons may play an important role in the natural tendency for renal function to deteriorate. Nevertheless, recent studies suggest that these glomerular hemodynamic events may not be the final common pathway for the natural deterioration of renal function, as was once thought. With regard to the general management of patients with impaired renal function, recent evidence suggests that controlling systemic blood pressure, reducing dietary protein and phosphorus intake, and controlling hyperlipidemia may be effective in slowing the loss of renal function. PMID- 2195257 TI - Choice of antibiotics, pharmacokinetics, and dose adjustments in acute and chronic renal failure. AB - A multitude of antimicrobial agents have become available over the past two decades. Appropriate use of these drugs demands not only an understanding of the antimicrobial spectrum of the agent but of the necessary dose adjustments because of renal or hepatic impairment. The use of computer-assisted pharmacokinetic modeling for dosing potentially toxic drugs such as aminoglycosides and vancomycin should be utilized whenever possible. PMID- 2195258 TI - Acute uric acid nephropathy. AB - Uric acid, as the end-product of purine metabolism in humans, presents a clinical problem because of its relative insolubility, particularly in the acid environment of the distal nephron of the kidney. As a result, states of enhanced purine catabolism increase the urate load on the kidney, leading to intrarenal precipitation. Major causes of increased purine metabolism are malignancies with rapid cell turnover, such as leukemias and lymphomas, and the added acceleration of cell lysis that occurs with chemotherapy and radiation. Serum urate levels rise rapidly, and acute renal failure occurs as a consequence of tubular deposition of urate and uric acid. The keys to the diagnosis of acute uric acid nephropathy are the appropriate clinical setting of increased cell lysis, oliguria, marked hyperuricemia, and hyperuricosuria. A urinary uric acid-to creatinine ratio greater than 1 helps to distinguish acute uric acid nephropathy from other catabolic forms of acute renal failure in which serum urate is elevated. Preventive treatment involves pharmacologic xanthine oxidase inhibition with allopurinol and alkaline diuresis. Occasionally, acute renal failure occurs despite allopurinol because of the tubular precipitation of the precursor metabolites, such as xanthine, which accumulate with xanthine oxidase inhibition. Dialysis therapy may be required both to correct azotemia and to reduce the body burden of urate. Hemodialysis is preferred because it can achieve greater clearance than other dialysis modes. PMID- 2195259 TI - Diagnosis and management of acute tubular necrosis. AB - The term acute tubular necrosis refers to those forms of acute renal failure that occur in association with ischemic or hypoxic injury or exposure to nephrotoxic substances. This article discusses the various alternative classifications that are based solely on the clinical setting in which the acute renal failure occurs, and the types of therapies used in the management of them. PMID- 2195260 TI - Diagnosis and management of glomerulonephritis and vasculitis presenting as acute renal failure. AB - Acute and rapidly progressive renal failure is caused by a number of pathogenetically distinct types of glomerulonephritis, some of which are associated with systemic vasculitis. In a given patient, accurate diagnosis of the specific type of glomerulonephritis is essential for optimum treatment. Making a specific diagnosis usually requires renal biopsy or serologic analysis. The two categories of treatment for glomerulonephritis are (1) treatment for the pathophysiologic complications of glomerulonephritis, such as hypertension, fluid overload, and uremia, and (2) treatment for the inflammatory injury, which usually employs immunosuppression with steroids and cytotoxic drugs. PMID- 2195261 TI - Drug-induced nephropathies. AB - Drug-induced renal disease is a common problem. Drugs cause several renal syndromes, such as prerenal azotemia, fluid and electrolyte abnormalities, acute tubular necrosis, acute interstitial nephritis, and chronic interstitial nephritis. Acute renal failure due to acute tubular necrosis is the most common syndrome and is most frequently caused by aminoglycoside antibiotics, radiographic contrast agents, and amphotericin B. Avoidance of these drugs in volume-depleted or hypotensive patients with preexisting renal disease or in those receiving multiple nephrotoxic drugs is the most effective way to reduce nephrotoxicity. Acute interstitial nephritis is an immune process that is most commonly caused by penicillins, diuretics, allopurinol, nonsteroidal anti inflammatory drugs, cimetidine, and sulfonamides. Prompt recognition of the disease and cessation of the responsible drug are usually the only necessary therapy. Chronic interstitial nephritis is most often seen after prolonged use of several different types of analgesic agents, including aspirin, acetaminophen, and nonsteroidal anti-inflammatory drugs. These patients develop recurrent papillary necrosis and eventually chronic renal failure. They are also at risk of developing transitional cell carcinomas of the urinary collecting system. Some patients who are receiving cyclosporine also develop chronic renal failure due to interstitial fibrosis. PMID- 2195262 TI - Acute renal failure due to urinary tract obstruction. AB - Urinary tract obstruction is a frequent cause of acute renal failure that is potentially life threatening but reversible, if it is promptly recognized and corrected. The level of urinary tract obstruction is variable, dependent on the underlying disease, and may range from the loop of Henle to the urethral meatus. Clinical manifestations are most commonly due to renal failure, but the history and physical examination can aid in determining the localization and cause of the obstruction. Laboratory findings may suggest urinary tract obstruction as the etiology for acute renal failure. Radiologic procedures, most prominently ultrasonography, can establish the diagnosis. Treatment is variable, but patient management may need to be altered during the postobstructive phase of urinary tract obstruction owing to physiologic response to reestablishment of urine flow. PMID- 2195263 TI - The hepatorenal syndrome. AB - HRS occurs frequently in patients with advanced cirrhosis of the liver and fulminant hepatitis. The pathogenesis of HRS is not clearly understood; reduced effective plasma volume and intense renal cortical vasoconstriction seem to have important roles. The HRS is a diagnosis by exclusion, and it [table: see text] is often difficult to differentiate this entity from prerenal azotemia and ATN. The HRS is characterized by its relentless progression and usually fatal outcome. The essential steps in the management of HRS are to identify and correct the precipitating factors leading to HRS and avoidance of potential hepatotoxic and nephrotoxic drugs. Patients with potentially reversible liver diseases should be treated aggressively. Volume expansion is important and should be tried first, even though hypovolemia may be not clinically evident. Dialysis may benefit patients with fluid overload and electrolyte imbalance or those awaiting liver transplantation. In selective cases, peritoneovenous shunt may be of value. Liver transplantation is the only curative therapy available at present. PMID- 2195264 TI - Principles, uses, and complications of hemodialysis. AB - Hemodialysis replaces missing renal function, and it does so incompletely. Current technology provides for reliable and flexible treatment strategies guided by patient's well-being and careful evaluation of plasma urea concentrations. Hemodialysis is indicated in many medical emergencies, notably fluid overload and hyperkalemia, and all types of renal failure. Hemodialysis requires a sizable effort and a significant commitment of time by both patients and professionals and is not suited for every patient with renal insufficiency. Notable treatment related side effects include cramps, hypotension, problems with blood access, and reactions to dialyzer membrane materials. Far from treating underlying disease, hemodialysis extends life and permits the expression of much progressive multisystem disease. Cardiovascular disease is the most common comorbid condition and cause of early mortality. PMID- 2195265 TI - Diagnosis and management of bone disorders in chronic renal failure and dialyzed patients. AB - Renal osteodystrophy is multifactorial. Decreased calcium absorption from the GI tract, secondary to low calcitriol levels; hyperphosphatemia; skeletal resistance to the action of parathormone; and aluminum deposition on the surface of the bones are its main pathogenetic mechanisms. Its biochemical features include abnormalities in serum calcium, phosphate, alkaline phosphatase, parathormone, calcitriol, and aluminum concentration. Radiographic methods are of little use in the characterization of the type of osteodystrophy present, but they may be of help in assessing mineral loss from the skeleton. Clinical manifestations are from bones (pain, deformities, fractures) or from metastatic calcifications. Bone biopsy is the definitive means of diagnosis. The main histologic types of osteodystrophy include osteitis fibrosa, osteomalacia, mixed form (with features of both osteitis fibrosa and osteomalacia), and aluminum osteodystrophy (presenting as either osteomalacia or aplastic lesion). The management of renal osteodystrophy should address all the pathogenetic mechanisms. Correction of the abnormalities in calcium and phosphate metabolism and prevention of aluminum osteodystrophy are the cardinal rules of management. Specific measures (parathyroidectomy, chelation of aluminum) have clear-cut indications and usually require a bone biopsy. PMID- 2195266 TI - Continuous arteriovenous hemofiltration. AB - CAVH is a bedside form of dialysis that is used in the treatment of fluid and electrolyte disorders seen in critically ill patients. The major advantages of the procedure include (1) gradual, continuous therapy, which is ideal in hemodynamically unstable patients; (2) control of fluid balance; and (3) ease of administration in the ICU. The major disadvantages of CAVH include (1) a requirement for arterial access, (2) the need for anticoagulation, (3) the risks of infection from long-term indwelling vascular lines, and (4) the potential for significant volume depletion. The effectiveness of CAVH may continue to improve owing to technical developments in filter composition and the application of clinical tactics such as suction-assisted filtration, predilution fluid replacement, or regional heparinization. The next step in bedside dialysis is represented by CAVHD, which offers all of the advantages of CAVH as well as improved urea clearance. PMID- 2195267 TI - Physiology of the peritoneum. Implications for peritoneal dialysis. AB - Solute and water transport from blood to peritoneal cavity occur by diffusion and osmotic ultrafiltration, whereas absorption to blood via lymphatics negatively affects these two processes. This article delineates the physiology of peritoneal membrane and numerous factors that influence mass transport during peritoneal dialysis, thereby affecting its therapeutic efficacy. Benefits and limitations of continuous ambulatory peritoneal dialysis (CAPD) are discussed and compared to those of hemodialysis. Survival on CAPD, its complications and imperfections are reviewed in light of the widespread acceptance of the procedure. PMID- 2195268 TI - CAPD peritonitis. Incidence, pathogens, diagnosis, and management. AB - Peritonitis is a frequent complication of CAPD. Sixty percent of all patients on CAPD will have at least one episode of peritonitis during the first year of this mode of dialysis. Most of the episodes of peritonitis are caused by touch contamination of the dialysis tubing or by extension of the catheter exit site or tunnel infection. Coagulase-negative and coagulase-positive Staphylococcus are the two most common organisms, accounting for 50% or more of all CAPD peritonitis. Other gram-positive and gram-negative bacteria and fungi account for the rest. Intraperitoneal antibiotic treatments are usually effective in eradicating the infection. The choice of antibiotics depends on organisms isolated from cultured dialysate. Fungal peritonitis and, occasionally, Pseudomonas peritonitis require removal of the catheter to eradicate the infection. Prompt identification and treatment of peritonitis are essential to ensure success of a CAPD program. Although with newer techniques, like Y connector or ultraviolet light system, the rate of peritonitis has declined; however, it has still remained the major complication of the CAPD program. PMID- 2195269 TI - [Inhibins of the testis and ovary and their morphologic origin]. AB - During the last decade and especially during the last several years the question of the inhibin presence in the gonads of both sexes has been in the focus of researcher's interests. According to what has been known up to date the inhibins are produced by Sertoli cells in the testis and by granulosa cells in the ovary. The inhibin activity is many-sided. It inhibits the synthesis and the discharge of the FSH what also leads to the reduction of LH-RH content. Additionally it also inhibits the process of spermatogonium multiplication in the testis and of the progesterone multiplication in the ovary. In this paper a synthesis of the known facts from the histophysiologic aspect has been given, without taking into consideration the possible future clinical and therapeutic effects of these facts still being researched. PMID- 2195270 TI - Abdominal aortic aneurysm evaluation: comparison of US, CT, MRI, and angiography. AB - We studied 26 cases of abdominal aortic aneurysm with magnetic resonance imaging (MRI), computed tomography (CT), ultrasonography (US), and angiography. Data acquired were compared to those obtained at surgery. Diameter of the aneurysm was correctly defined in all cases by CT and MRI, while angiography underestimated the diameter of lesions without peripheral calcifications. Involvement of renal arteries was present in four cases and correctly diagnosed with MRI and angiography in all of them. CT did provide this information in three cases and US were not useful. Also, iliac arteries involvement was depicted by CT, MRI, and angiography in 10 out of 10 patients. Coronal sections of MRI provided comparable images to those of angiography. By comparing these different techniques we verified the good reliability of MRI as investigation tool for an accurate evaluation of aneurysms; its only limit lying in the poor capability of detecting calcifications. PMID- 2195271 TI - Subtraction technique for contrast-enhanced MR images of musculoskeletal tumors. AB - Vascularized malignant tissue, fat and hemorrhage may have similar intensities on Gd-DTPA-enhanced, T1-weighted MRI performed to evaluate musculoskeletal tumors. We describe a simple, rapid post-processing subtraction technique which resulted in improved definition of these tissues in 33 of 42 examinations. While the subtraction process is susceptible to complex patient motion, the improved contrast can be obtained without modifying standard pulse sequences. PMID- 2195273 TI - An observation of increased contrast due to both T1 and T2 weighting in a synthetic image. AB - An observation was made that subtracted images generated by an SR/IR interleaved pulse sequence on a low field strength magnetic resonance imager (M&D Technology Ltd, Aberdeen, Scotland) contained contrast between pathological and normal tissues that was not explained by either T1 or T2 weighting alone. A theoretical model for this image has been derived and its validity confirmed by phantom experiments. It is shown that the subtracted image is dependent on the product of T1 and T2 prolongation for contrast. This type of image might be of use in screening for unknown pathologies and such techniques may shorten routine patient imaging times. PMID- 2195272 TI - Magnetic resonance imaging of nasopharyngeal and paranasal sinus melanoma. AB - Malignant melanoma of the nasopharynx and paranasal sinuses is relatively rare. We retrospectively reviewed the magnetic resonance appearance of five cases and correlated this with the histopathological appearance. In all cases, the magnetic resonance (MR) images clearly demonstrated the precise anatomic extent of the tumor and were sensitive in assessing intracranial extension and invasion into surrounding structures, including the skull base. Three cases were reviewed for histopathological evidence of melanin, hemosiderin, and acute hemorrhage. One case was reviewed for melanin and hemorrhage only. The findings in this series suggest that melanoma of the nasopharynx and paranasal sinuses have extremely variable amounts of paramagnetic substances, both melanin and products of hemorrhage. T1 shortening appears to be more often a reflection of the paramagnetic effects associated with products of hemorrhage rather than the presence of melanin. PMID- 2195274 TI - Giant-cell tumor of the tibia in a child presenting as an expansile metaphyseal lesion with fluid-fluid levels on MR. AB - Approximately two percent of giant-cell tumors (GCT) occur in the skeletally immature. The patient presented is four years old with a cystic giant-cell tumor of the tibial metaphysis. Fluid-fluid levels are demonstrated on CT and MR and likely represent the underlying pathophysiology. PMID- 2195275 TI - [Treatment of Plasmodium falciparum malaria in Africa (except cerebral malaria)]. AB - Chloroquine is currently the drug of choice for treatment of acute attacks of Plasmodium falciparum malaria in chloroquine-sensitive areas. In areas of low level resistance, this drug may still be used (25 mg/kg of body weight in three days) in semi-immune patients. In case of failure, or in areas of high level resistance, quinine (25 mg/kg/day for 3 to 5 days) or, in spite of increasing resistance, Fansidar should be prescribed. Mefloquine, Fansimef and Halofantrine ought to be strictly prescribed to delay occurrence of resistance. Severe attacks require quinine by continuous intravenous infusion. Spleen enlargement does not usually require specific treatment unless poor tolerance is observed. Blood transfusions present a considerable risk of HIV transmission. Appropriate malaria treatment may avoid blood transfusions thus preventing HIV dissemination in Africa. PMID- 2195276 TI - [Evaluation of the efficacy of amino 4-quinolones in a chemoresistant zone. Proposals for new therapeutic schemes]. AB - The authors compare the respective therapeutic efficiency of chloroquine and amodiaquine in the treatment of Plasmodium falciparum malaria fever in urban dispensaries. Chloroquine has a constant rate of efficiency, whatever dosage and duration of treatment be and should be saved for home presumptive treatment of malaria fever. Amodiaquine at a dose of 35 mg/kg in 3 days leads to a noticeable clinical success (96.5 p.c.). It should be selected as drug of first to treat any malaria fever case biologically confirmed, in urban dispensaries. PMID- 2195277 TI - [Plasmodium falciparum chemoresistance. The situation in Africa in 1989]. AB - Between 1978 and 1989, some Plasmodium falciparum chloroquino-resistant (C.Q.R.) strains have been imported in all intertropical African countries. Evidence of sudden occurrence of C.Q.R. foci was obtained by some prophylactic or therapeutic failures, and culture of strains from non-immune travellers back in Europe or U.S.A., then by carrying out some field surveys. C.Q.R. heterogeneity is the rule in Africa, efficiency of other antimalarial drugs diminishes rapidly in the foci where C.Q.R. remains at high level, probably in relation with drug pressure. Non typical clinical manifestations raising of child death-rate death not avoidable by chloroquino-prophylaxis, confused therapeutic attitudes were all of them the main facts accompanying the occurrence of C.Q.R. in Africa. It is not possible nowadays to foresee the evolution of C.Q.R. situation and of its social consequences in low-immune African populations. PMID- 2195278 TI - Chemoprophylaxis of malaria: underlying principles and their realization. AB - Drug prophylaxis of malaria, first practised with quinine, became safer and simpler after the introduction of mepacrine and later chloroquine. The occurrence and spread of chloroquine resistance in Plasmodium falciparum rendered prophylaxis more difficult as it necessitated the use of alternative drugs, some of which were associated with major adverse reactions. The presence of resistance to sulfadoxine-pyrimethamine in some areas compounded the problem. The current repertoire of prophylactic drugs for routine use includes chloroquine, proguanil and mefloquine. The indications for which depend on the local sensitivity pattern of the malaria parasites, especially Plasmodium falciparum, duration of exposure, special risk factors and immune status. A closed look at these drugs, especially proguanil, suggests that their efficacy or safety can be increased by following sound pharmacokinetic principles. Chlorproguanil has so far not been used in keeping with its pharmacological characteristics. This drug holds considerable promise for improving the drug prophylaxis of malaria, particularly if it can be associated with a well, tolerated synergist. PMID- 2195279 TI - [Prevention of malaria in travellers and expatriates]. AB - Since the occurrence of the chloroquino-resistance, chemoprophylaxis for all is not anymore the sound principle to malaria prophylaxis for travellers and expatriates. Protection against malaria has now to be based on comprehensive actions (chemoprophylaxis, control of infecting bites, treatment of malaria cases as soon as first symptom occur), they have to be combined, as a whole or not, according to the area, the duration and the type of tropical stay, and even sometimes according to some parameters peculiar to an individual. The development of concepts concerning the epidemiology of human malaria and the use of antimalarial drugs, either as protective or curative, lead more and more to the necessity for any traveller or expatriate to take medical advice from a specialized physician. PMID- 2195280 TI - [Immunization against human malaria: present knowledge]. AB - The authors review different aspects of immunization against malaria according to the different stages of the parasitic cycle of Plasmodium falciparum: sporozoite vaccine preventing organism infestation, merozoite vaccine and gametocyte vaccines preventing the accomplishment of the sexual cycle. Progress of molecular biology and better knowledge of cellular immunity provide some prospects regarding parasitic vaccinology, thanks to genetic engineering. Recombinant vaccines in vitro, in vivo and synthetized are under study and provide the best prospects regarding immunization against human malaria. PMID- 2195281 TI - [Chemosensibility of Plasmodium falciparum in Africa south of the Sahara: evaluation of two and a half years' research at the Tropical Medicine Institute of the Health Service of the French Armed Forces]. AB - From March 1987 to June 1989, 194 isolates of Plasmodium falciparum were studied in vitro by the isotopic semi-microtest. 86.1% were resistant to chloroquine; 9.5% had a decrease of sensibility to quinine and 3.3% a decrease of sensibility to mefloquine. There was a positive correlation between I.C. 50 of the antimalarial drugs compared by pairs. PMID- 2195282 TI - [In vivo amodiaquine sensitivity of Plasmodium falciparum in the town of Cotonou and in the vicinity (Benin)]. AB - In the coastal area of Benin, where chloroquine resistant Plasmodium falciparum strains occur, 152 children in the Guezo military camp (Cotonou) and 448 children in a fishermen village (Ekpe), on the southern bank of lake Nokoue, are examined. The falciparum malaria infected children (29 and 135 respectively) have received 35 mg/kg body weight of amodiaquine (Flavoquine) divided in three consecutive daily doses. Only one child among the 69 treated having a parasitemia higher than 1,000/mm3 failed to be cured. The amodiaquine tolerance is excellent for, respectively, 64% and 72% of the children. Minor side-effects are rapidly regressive. The frequency of conjonctival hyperhemia as an amodiaquine side effect is nevertheless relatively high (14.7%) in the children regularly treated with this drug, e.g. those of the military camp, while it is rare (0.8%) in others, e.g. in the fishermen village children where amodiaquine is unusual as an antimalarial medicine. PMID- 2195283 TI - [Evaluation of Plasmodium falciparum susceptibility to chloroquine and amodiaquine using a simplified, in vivo, 7-day test in southern Cameroon]. AB - Plasmodium falciparum susceptibility to chloroquine and amodiaquine at a posology of 25 mg/kg per os in 3 days was evaluated in the pupils of 6 primary schools of South-West Cameroon during the first semester 1989. Parasitic index was 75%. Plasmodium falciparum was present in 96% of the infections 24% of the 357 children treated with chloroquine were carriers of trophozoites at D3 and 17% at D7. Complete resistance, at level R III, was observed in 4% of the children. By the 55 children treated with amodiaquine, 13% and 10% were carriers of few trophozoites at D3 and D7. The significance of these results is discussed. PMID- 2195284 TI - [Epidemiologic aspects of malaria in Gabon]. AB - The authors report the results of 3 sample surveys carried out in Libreville, Ngounie and Haut-Ogooue Provinces to evaluate the main malarial indexes among 0 to 15 years old children in Gabon. These investigations would suggest that malaria is mesoendemic in the three areas. The systematic presumptive antimarial treatment of fever attacks is widely used in Libreville but not so frequent in rural areas. PMID- 2195285 TI - [Evaluation of malarial indices in the forest region of Djoum (southern Cameroon)]. AB - The authors report the results of a sample survey carried out in Djoum to evaluate the main malarial indexes among 0-15 years old children. These investigations suggest that malaria is hyperendemic in this forestry area, at the end of the dry season. PMID- 2195286 TI - [Imported malaria at hospitals in Bordeaux (France) in 1987 and 1988. Report of 185 cases]. AB - 100 cases of imported malaria were registered in Hospitals of Bordeaux in 1987 and 85 in 1988. Origin of infestation is Africa in 88 p.c. of the cases mainly from Central Africa (50 p.c.) in 1987 and western Africa (67 p.c.) in 1988. The most frequent species was Plasmodium falciparum 73 p.c. in 1987 and 82 p.c. in 1988. Admitted cases in Bordeaux were mainly French (81 p.c.) with a significant male prevailing and young adults. Mean age was 29 for Europeans and 19 for the others mainly Africans. Infestation risk is in close correlation with the duration of stay in endemic zones. It is maximum for stays between 2 and 11 months. Delay for first symptoms to appear following return from an endemic zone depends of species concerned during the first month, 83 p.c. of malaria fever at Plasmodium falciparum during the second quarter, 50 p.c. of fever at Plasmodium vivax, and after one year or more 40 p.c. at Plasmodium ovale. Only 1/4 of the cases were diagnosed during the first 48 hours. Delay in diagnosing may be prolonged and is in relationship with Plasmodium falciparum chemoresistance and self-medication. 21 strains of Plasmodium falciparum were chloroquinoresistant in vitro: 1 from French Guyana, 9 from Western Africa, and 11 from Central Africa. The strain from Guyana was also less sensible to quinine with a IC 50 = 480 nmol/l. PMID- 2195287 TI - [Plasmodial indices and malarial placentopathy in 299 parturients in Central Africa]. AB - 229 parturients were screened for malaria by blood smear test and examination of placenta (placental apposition and anatomopathological examination). Primiparous show higher sensibility to infection, with a weight deficit for newborn as a consequence of it. Placenta examination enables to diagnose twice as much malarial infestation than blood smear. Placental apposition appears to be an interesting indicator from the point of view of diagnosis and epidemiology. PMID- 2195289 TI - Defining mental retardation from an instructional perspective. AB - A definition of mental retardation developed under the aegis of the instructional paradigm was presented. Its purpose and use is to (a) clarify the task of personnel who work with persons who have been identified as mentally retarded and (b) provide a concept that unifies apparently discrete instructional constructs. This definition can also help mold the perceptual patterns of young persons entering the field by establishing expectations that focus on the provision of instruction. PMID- 2195288 TI - [The Quantitative Buffy Coat test (Q.B.C. test). Monofluo Kit Falciparum. Comparative value in the rapid diagnosis of malaria]. AB - New emerging atypical forms of malaria, characterized by weak parasitemia, among peoples without premunition, back from Plasmodium falciparum resistant areas, make it necessary to use rapid, sensitive, reliable methods of parasitologic diagnosis. This work concerned two different populations: 394 expatriates back from a 4 months stage in endemic areas. 12 patients admitted for suspected of proved malaria. Authors have studied, by double blind method, versus thin film, two fluorescent techniques: a direct immunofluorescence, the Monofluo kit Falciparum of Diagnostic Pasteur. A nucleic acid fluorescence, on blood samples centrifuged in capillary tubes, the Q.B.C. test of Becton-Dickinson. Both methods seem of great interest for epidemiological surveys. The Q.B.C. test has showed more sensitivity than the thin film: it's rapidity of realisation indicates it for urgent diagnosis. PMID- 2195290 TI - Medicaid versus state funding of community residences: impact on daily life of people with mental retardation. AB - The unintended effects on quality of life that flow from decisions regarding funding sources used to support community-based residential programs were documented. Results show that community residence program structures play an important role in determining quality of life after deinstitutionalization. Clients living under program structures flowing from the Medicaid ICF/MR funding source were less active and involved in life than were clients living in programs funded by non-Medicaid state sources. We hypothesized that the reason for this differential outcome was the result of Medicaid funding regulations and their interpretation, which create an institutional-like set of program structures leading to restrictive care patterns. PMID- 2195291 TI - Zinc metabolism in patients treated with captopril versus enalapril. AB - Several zinc parameters were assessed in 13 patients with essential hypertension who were chronically taking only captopril (six subjects) or enalapril (seven subjects), as well as in six untreated hypertensives, and nine healthy controls. Serum zinc levels were comparable in all groups. Twenty-four-hour urinary zinc excretion was significantly increased in the captopril-treated patients compared with the other three groups. The zinc:creatinine ratio in 24-hour urine was significantly increased in both captopril and enalapril groups, but was significantly greater in the former. Although plasma zinc concentrations were comparable in all groups, red blood cell (RBC) zinc values were significantly decreased in the captopril group compared with the other three groups. We conclude that (1) although both captopril and enalapril produce renal zinc loss, this loss is far greater in patients receiving captopril; and (2) captopril administration over 3 months or more generates RBC zinc depletion. PMID- 2195292 TI - Metabolic changes in rats fed a low protein diet during post-weaning growth. AB - Metabolic changes in rats fed a low protein diet were investigated during 3 weeks after weaning using lactalbumin (LP) as dietary protein source. The energy intake was higher and the weight gain lower in rats fed the low protein diet (6%, LP group) than in control rats (13% lactalbumin, C group). Low protein diet induced no changes in plasma glucose, free fatty acids, or triacylglycerol concentrations; however, plasma protein and urea concentrations were lower in LP than in C rats. Plasma free T3 was higher in LP than in C rats (+38%, day 21) and insulin progressively decreased during the experimental period (-56%, day 21) without change in glucagon. Liver glycogen and triacylglycerol concentrations (+40% and +180%, respectively, day 21), and cytosolic and mitochondrial redox states increased (+100% and +100%, day 21), and protein concentration was decreased (-15%, day 21). Pyruvate kinase (PK) and malic enzyme activities were higher in LP than in C rats throughout the experiment (+80% and +210%, respectively, day 21), and glucose-6-phosphate dehydrogenase (G6PDH) activity progressively decreased (-65%, day 21). Phosphoenolpyruvate carboxykinase (PEPCK) activity increased after 2 weeks on a LP diet (+35%, day 21) and fatty acid synthetase (FAS) activity increased only during the first week on the diet (+100%, day 7). Such hormonal and metabolic changes appeared to be associated with the development of a futile energy-wasting cycle between pyruvate and phosphoenolpyruvate. PMID- 2195293 TI - Amniotic fluid prolactin in the third trimester of pregnancies complicated by gestational or pregestational diabetes mellitus. AB - Amniotic fluid concentrations of immunoreactive prolactin were measured during the third trimester in 184 diabetic gravidas and correlated with concurrent levels of prolactin in maternal plasma. Prolactin measurements concorded with previously published estimates in normal gravid women and averaged 825 +/- 32 ng/mL (mean +/- SEM) in amniotic fluid and 168 +/- 6.5 ng/mL in simultaneously sampled plasma. Cross-sectional and longitudinal analyses indicated that the prolactin levels in amniotic fluid of pregnant diabetics declined significantly between weeks 32 and 40 of gestation, whereas plasma levels did not change consistently during the same interval. Mean values for amniotic fluid prolactin did not correlate with simultaneous prolactin concentrations in plasma, nor with maternal age, clinical estimates of polyhydramnios, amniotic fluid creatinine content, or lecithin/sphingomyelin (L/S) ratios or subsequent birth weight of the offspring. Clear-cut correlations with overall maternal glucose regulation could not be demonstrated. However, subtle effects may be operative since amniotic fluid prolactin displayed weak but significant correlations with concurrent levels of maternal plasma glucose, and mean values for hemoglobin A1c (HbA1c) but not with mean values for fasting plasma glucose (FPG). Amniotic fluid prolactin concentrations were significantly greater in patients with pregestational diabetes (White classes C, D, and F) than in women with gestational diabetes mellitus (GDM) (our classes A1, A2, and B1). The differences could not be accounted for by differences in metabolic regulation, maternal age, or weights of these two populations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2195294 TI - Successful banking of pancreatic endocrine cells for transplantation. AB - To determine optimal freezing and thawing conditions for rat pancreatic endocrine cells (PEC) and insulinoma cells, five different cryopreservation protocols were compared in this study. PEC and insulinoma cells were cooled at rates of between 0.3 degrees C/min and -5 degrees C/min to -70 degrees C in the presence of 10%, 15%, or 20% dimethylsulfoxide (DMSO) with a programmable temperature controller and then transferred to liquid nitrogen for storage. Frozen cells were thawed by either rapid (in 37 degrees C water bath) or slow (in air) thawing procedure. One hour after the thawing process, cellular viability was determined by trypan blue dye exclusion. The viability results for PEC and insulinoma cells were similar and showed that a slow cooling rate at -0.3 degrees C/min in combination with a rapid thawing in 37 degrees C water bath gave the best results, with up to 80% cellular viability. Cryoprotectant DMSO used at 10% concentration was the most effective among the three concentrations tested. Later, transplantation studies were performed with PEC cryopreserved with the best protocol, which is -5 degrees C/min to 4 degrees C, held for 3 minutes, -0.3 degrees C/min to -7 degrees C, held for 3 minutes, -0.3 degrees C/min to -40 degrees C, and -5 degrees C/min from -40 degrees C to -70 degrees C in 10% DMSO with a programmable temperature controller then transferred to liquid nitrogen for storage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2195296 TI - Effect of interleukin-1 and tumor necrosis factor/cachectin on glucose turnover in the rat. AB - We studied the effect of recombinant human interleukin-1 beta (IL-1) and recombinant human tumor necrosis factor alpha/cachectin (TNF) on glucose kinetics in healthy rats by means of a primed constant infusion of D-(6-3H)glucose and D [U-14C]glucose. During the isotope (6-hour) and monokine (4-hour) infusion, plasma levels of glucagon and insulin were determined and correlated with changes in glucose metabolism. The rates of glucose appearance (Ra) and disappearance (Rd) were elevated only with IL-1 and were associated with an increase in glucagon and a concomitant decrease in the ratio of insulin to glucagon. Plasma glucose concentration was increased early after IL-1 administration and coincided with the peak in the Ra. The augmentation of the metabolic clearance rate (MCR) and percent of flux oxidized by IL-1 suggest that this monokine induces the utilization of glucose as a substrate. TNF administration failed to modify the Ra or Rd, percent of flux oxidized, or MCR. TNF-treated rats increased the percent of glucose recycling, but not the total rate of glucose production. The results of this experiment suggest that endogenous macrophage products participate in the diverse alterations of carbohydrate metabolism seen during injury and/or infection. PMID- 2195295 TI - The thermic effect of feeding in older men: the importance of the sympathetic nervous system. AB - We have previously published direct evidence that approximately one third of the thermic effect of feeding (TEF) in young healthy men can be accounted for by the meal-induced increment in sympathetic nervous system (SNS) activity. The elderly are known to have abnormal beta-adrenergic mechanisms and blunted responsiveness to sympathetic stimulation. Therefore, we postulated that the elderly might also have a blunted thermic response to a meal. In the present study, we evaluated the TEF in 25 young (age, 29.4 +/- 4.6 years) and 12 older (66.6 +/- 7.0 years), healthy weight-stable, untrained, nonsmoking men on no medications. Energy expenditure (ventilated hood system) and SNS activity (arterialized plasma catecholamine concentrations and norepinephrine [NE] kinetics) were measured before and following ingestion of an 800-kcal high-carbohydrate meal. At baseline, arterialized plasma NE concentration (P = .001) and appearance rate (P = .05) were 40% and 28% higher, respectively, in the elderly. Resting energy expenditure was related to fat-free mass (r = .54, P less than .01), and was 21% lower in the older men (P less than .01). Energy expenditure increased in both groups following the meal, but this TEF was 48% lower in the older men (P less than .001). This reduced TEF observed in the older subjects was associated with only a slight, nonsignificant, blunting of the SNS response to the meal. The TEF was related to the arterialized plasma NE appearance rate in the young, but not the older group. The TEF was unrelated to either glucose or insulin concentrations in either group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2195297 TI - Nutritional status affects renal 3-methylhistidine handling in humans. AB - The plasma concentration of 3-methylhistidine (3MH) has been used in the assessment of nutritional status. Because urinary excretion is the sole route of elimination, and hence a potential determinant of the plasma concentration, 3MH renal handling was examined under different nutritional conditions. Ten obese women consumed a meat-free maintenance energy diet for 4 days before undergoing a 21-day total fast, after which they were assigned into two groups (n = 5) that received 7 days of hypocaloric feeding with 80 g of either milk protein or carbohydrate. 3MH excretion and plasma levels decreased in parallel during fasting and protein refeeding, suggesting that the plasma concentration accurately reflected a decrease of myofibrillar protein turnover, but carbohydrate refeeding was associated with a 31% increase in plasma 3MH (P less than .05) despite a concurrent 28% decrease in its excretion (P less than .05). This was due to a 41% decrease in 3MH renal clearance (P less than .05). Creatinine and urea clearances changed insignificantly in all diet periods. Plasma histidine (HIS) concentrations decreased with fasting and carbohydrate refeeding (P less than .05). 3MH clearance was found to be related to the plasma HIS/3MH concentration ratio (r = .60, P less than .001). Under some circumstances, an altered plasma HIS concentration appears to influence renal 3MH clearance and hence its plasma concentration. PMID- 2195298 TI - Metabolic response to egg white and cottage cheese protein in normal subjects. AB - In type II diabetic subjects, we previously demonstrated differences in the serum insulin, C-peptide, and glucagon response to ingestion of seven different protein sources when administered with 50 g of glucose. The response was smallest with egg white and greatest with cottage cheese protein. In the present study, we compared the responses to 50 g of the above two proteins ingested without glucose in normal male subjects. We also determined the proportion of each ingested protein converted to urea nitrogen. The incremental area response integrated over 8 hours for serum insulin, C-peptide, glucagon, alpha-amino-nitrogen (AAN), and urea nitrogen were all approximately 50% less following egg white. This was associated with a 50% smaller conversion of protein to urea. Overall, 70% of the cottage cheese but only 47% of the egg white protein could be accounted for by urea formation. Most likely the smaller hormonal response to egg white is due to poor digestibility of this protein. PMID- 2195299 TI - The effect of ergometrine on breast feeding. AB - A randomised, controlled trial of 1429 women was carried out to compare 'active' management of the third stage of labour, using i.v. Ergometrine 0.5 mgs, with a method of 'physiological' management, in women at 'low risk' to haemorrhage. A separate sub-study, with 168 women in each of the two groups, examined the possible effects of Ergometrine on serum prolactin levels and the duration of breast feeding. No difference was found in peak (post-suckling) serum prolactin levels taken from 126 women between 48 and 72 hours postnatal. Further studies with larger sample sizes would give a more dependable result. Women who did not receive the drug Ergometrine were more likely to continue breast feeding for longer than four weeks than those who did (p less than 0.05). It is recommended that this drug should not be given routinely to women intending to breast feed. PMID- 2195300 TI - Nutritional requirements in pregnancy: what should the pregnant woman be eating? AB - It is now recognised that 'eating for two' during pregnancy is not a sound practice. However, what should a pregnant woman eat? This article reviews firstly the available literature on the food intake of healthy women producing a healthy baby, and secondly the literature on the calculation of needs from what is known of the physiological demands of pregnancy. PMID- 2195301 TI - Viability of Salmonella in bone meal. AB - The ability of Salmonella to survive varying concentrations of sodium metabisulphite incorporated into bone meal (rendered animal by-product) was investigated. No viable Salmonella was detected after 4 days of exposure of the micro-organisms to 5,000 ppm of sodium metabisulphite. The minimum killing concentration of metabisulphite was also established at 4,000 ppm. However, the killing effect of the metabisulphite was moisture-dependent, being most potent at a moisture level of 8 to 12%. PMID- 2195302 TI - Effects of cisplatin and two novel palladium complexes on Candida albicans. AB - The effects of cisplatin and two novel palladium complexes of possible cancer chemotherapeutic value on the yeasts Candida albicans and Saccharomyces cerevisiae were studied. All three drugs had growth inhibitory effects. Significant effects on uridine uptake by all three drugs were seen, but inhibition of thymidine uptake was either small or non-existent. A marked stimulatory effect of all of the complexes on cell respiration was observed after 16 h growth in their presence. In some cases immediate stimulation of cellular respiration was invoked on drug treatment. The palladium complexes caused extensive mycelial growth of C. albicans whilst cisplatin induced pseudohyphal growth. Results are discussed with respect to possible mechanisms of action of the drugs. PMID- 2195303 TI - Persistence of gluconeogenesis in Escherichia coli poisoned by oxidant stress. AB - The poisoning (inhibition of growth rate) of Escherichia coli by 4.2 atmospheres of hyperbaric oxygen was less when the culture energy source was glucose, fructose-6-phosphate, or glycerol, compared to pyruvate, oxaloacetate, or amino acids. This was consistent with previous indirect data which pointed to impaired gluconeogenesis in the toxicity mechanism. However, the three enzymes unique to gluconeogenesis (fructose-1, 6-diphosphatase, phosphoenolpyruvate synthase and phosphoenolpyruvate carboxyl-kinase) were not decreased in specific activity to a biologically significant extent in cell-free extract of cells poisoned by hyperbaric oxygen. Net glycogen synthesis in vivo was not decreased from glycerol, pyruvate or oxaloacetate, compared to glucose in cells exposed to oxidant stress from hyperbaric oxygen or 1 mM aerobic paraquat with cells exposed as exponentially growing cells prior to assay or as resting cells during the assay. PMID- 2195304 TI - Effect of phosphate buffer agar on the number of UV-induced mutations to streptomycin resistance in Escherichia coli strains. AB - The number of UV-induced mutations to streptomycin resistance in Escherichia coli B/r cells depends on the post-irradiation incubation medium. When cells are incubated on phosphate buffer agar (PBA) as opposed to brain heart infusion agar (BHI), there is an irreversible loss in the number of potential streptomycin resistant mutants which develop. This decrease in mutant numbers is known to occur without a corresponding loss in overall cell viability and cannot be explained in terms of the kinetics of dimer excision. Recent studies have indicated that pyrimidine dimers are the substrate for this repair on PBA. The genetics of PBA repair was investigated by observing the influence of the post irradiation incubation medium (PBA vs BHI) on the number of streptomycin resistant mutants which develop in E. coli strains deficient in various repair pathways. A recB and recC strain (WP3 recB trp-; WP7 recC trp-) showed repair of potential streptomycin resistant mutants similar to that of B/r when incubated on PBA following irradiation. The medium had no effect on the number of mutants expressed in an excision deficient uvrA- strain (WP2 uvrA trp-) or a polymerase I mutant (P3478 polA thy-). This was interpreted to mean that the loss of streptomycin resistant mutants on PBA involves the excision repair pathway and is dependent on the polA gene product, polymerase I. PMID- 2195305 TI - Michigan Academy of Family Physicians. The "family doc" faces the 90s. PMID- 2195306 TI - Electronic fetal heart rate monitoring during labour: does it prevent perinatal asphyxia and cerebral palsy? PMID- 2195307 TI - Osteomyelitis: approaching the 1990s. PMID- 2195309 TI - National Center for AIDS Statistics. PMID- 2195308 TI - Adenosine. PMID- 2195310 TI - On Medicare market reform and payment adjustments. PMID- 2195311 TI - [Bacterial recolonization in the guided regeneration of the inter-radicular periodontal tissues]. AB - The present experimental study has been undertaken in order to analyse clinically and microbiologically the formation of new periodontal attachment in class II furcation lesions in mandibular molars, comparing healing after surgical conventional therapy and after guided periodontal tissue regeneration technique using non-resorbable membranes and evaluating at the same time, with cultural anaerobic technique, the influence on healing of the bacterial recolonization of some periodontally pathogenic species. Clinical results have demonstrated that, after therapy, may occur a certain discrepancy between soft and hard tissue regeneration and that the bone tissue shows a different pattern of apposition in the horizontal and vertical direction. Microbiological data have underlined the significance of surgical instrumentation in the guided inter-radicular periodontal tissue regeneration and have confirmed the necessity of maintaining the healing sites free from the main periodontal pathogens. PMID- 2195312 TI - [Local anesthesia in childhood. Clinico-statistical studies]. PMID- 2195313 TI - [The clinical and therapeutic approach in oromaxillofacial pain]. AB - The general outlines and manifold aspects of oromaxillofacial pain are described on the basis of personal experience. Diagnostic difficulties are also outlined with emphasis on the basic features of symptomatic and essential forms. Finally the treatment protocol adopted is described with particular reference to symptomatic neoplastic forms. PMID- 2195314 TI - [Integrated instrumental diagnosis in salivary gland pathology]. AB - The role of instrumental practice, especially using pictures, in the diagnosis of salivary gland conditions has been examined. A number of remarks arise out of the evaluation of possibilities and limitations of the various techniques. In general, the aid these offer when clinical medicine alone fails to achieve accurate diagnosis; then need to proceed from the simpler, more innocuous techniques to other more complex, invasive ones only when the limitations of the former prevent a complete classification of the features of the lesion. Used rationally, integrated instrumental diagnosis represents an extra tool available to the clinician. PMID- 2195315 TI - [Periodontal therapy. II. The possible interpretations of the therapeutic results from surgical and nonsurgical treatment]. AB - The authors put forward four different explanations to justify the similarity of published results on the efficacy of different techniques of periodontal therapy. It is stressed that over and above the purely doctrinal evaluation of results obtained using different forms of periodontal therapy, it is indispensable to draw up a treatment protocol for each case taking into account the specific conditions and requirements of the patient to be treated. PMID- 2195316 TI - [Dentinal hypersensitivity: the etiopathogenetic mechanisms and treatment. The current state of knowledge]. AB - The anatomical and physiological characteristics of the pulpal and dentinal sensitive system are described. Some different theories about the transmission of the dentinal sensitivity are also explained. Finally, the different desensitizing agents, their main characteristics and mechanisms of action are analyzed. PMID- 2195317 TI - [Odontogenic keratocysts: the anatomicopathological characteristics and the clinical and therapeutic aspects. A review of the literature]. AB - The paper contains an extensive review of the literature on keratocysts, a variety of odontogenic cysts with unique clinical features. The anatomo pathological, radiological and clinical characteristics of the cysts are examined in order to aid diagnosis, which remains however solely histological. In addition, the paper discusses various therapeutic solutions which appear to offer the greatest guarantee that relapses typical of these cystic formations do not occur. PMID- 2195318 TI - Reduced membrane protein associated with resistance of human squamous carcinoma cells to methotrexate and cis-platinum. AB - A membrane protein recognized by monoclonal antibody SQM1 was identified in human squamous carcinomas, including those originating in the head and neck (SqCHN), lung and cervix. Cell lines derived from SqCHN of previously untreated patients expressed high amounts of this protein. In contrast, many cell lines established from SqCHN of patients previously treated with chemotherapy and/or radiation showed diminished amounts of this SQM1 protein. The expression of SQM1 antigen was determined in several SqCHN cell lines made resistant by exposure to methotrexate (MTX) in vitro. The parent cell lines all exhibited strong binding to SQM1 antibody. The MTX-resistant sublines showed much lower membrane binding of SQM1. The lowest SQM1 reactivity was found in cell lines with high resistance to MTX and with diminished rate of MTX transport. Some highly MTX-resistant cell lines which had high levels of dihydrofolate reductase, but which retained a high rate of MTX transport, also retained high levels of SQM1 binding. Reduced SQM1 protein was also found in SqCHN cells which developed resistance to the alkylating drug cis-latinum (CDDP) and which showed reduced membrane transport of CDDP. Cell growth kinetics and non-specific antigenic shifts were not responsible for the differences in SQM1 binding between the parent cell lines and their drug resistant sublines. The finding of a novel protein which is reduced in cells resistant to MTX and CDDP could contribute to our understanding of the basic mechanisms of drug resistance. By detecting SQM1 protein in clinical specimens, it may be possible to monitor the development of drug resistance in tumors. PMID- 2195320 TI - Pelvic mass as the initial symptom of ovarian leiomyoma. PMID- 2195319 TI - Possible involvement of NADPH requirement in regulation of glucose-6-phosphate and 6-phosphogluconate dehydrogenase levels in rat liver. AB - Previous studies examining regulation of synthesis of Glucose-6-Phosphate and 6 Phosphogluconate dehydrogenase in rat liver have focussed on the induction of these enzymes by different diets and some hormones. However, the precise mechanism regulating increases in the activities of these enzymes is unknown and the factors involved remain unidentified. Considering that many of these metabolic conditions occur simultaneously with the increase of some NADPH consuming pathway, in particular fatty acid synthesis, we suggest that the activities of Glucose-6-Phosphate and 6-Phosphogluconate dehydrogenase could be regulated through a mechanism involving changes in the NADPH requirement. Here, we have studied the effect of changes in the flux through different NADPH consuming pathways on the NADPH/NADP ratio and on Glucose-6-Phosphate and 6 Phosphogluconate levels. The results show that: i) an increase in consumption of NADPH, caused by activation of fatty acid synthesis or the detoxification system which consumes NADPH, is paralleled by an increase in levels of these enzymes; ii) when increase in consumption of NADPH is prevented, Glucose-6-Phosphate and 6 Phosphogluconate dehydrogenase levels do not change. PMID- 2195321 TI - Primary pulmonary hypertension: modes of diagnosis and aggressive treatment with vasodilators. AB - In the last decade we have made great strides in our understanding of the clinical presentation and findings, natural history, and treatment of patients with primary pulmonary hypertension. Recognizing the tendency for in situ thrombosis in many of these patients now gives strong support to the recommendation that anticoagulants be used for patients who are felt to have underlying pulmonary artery thrombosis. Vasodilators in adequate doses can be demonstrated to cause substantial reductions in pulmonary artery pressure and pulmonary vascular resistance which causes regression in right ventricular hypertrophy and marked clinical improvement. There is still much to be accomplished in this field: a major challenge is to diagnose pulmonary hypertension in patients earlier, at a more treatable stage, and to develop effective treatments for patients with severe right ventricular dysfunction refractory to vasodilator treatment. PMID- 2195322 TI - [The role of lipids in the interaction of influenza virus with the host cell]. AB - The published data on the lipids composition of influenza virus, the significance of lipid-protein interactions for support of the virion structure are reviewed. The roles of viral and cellular membrane lipids in the different stages of viral interaction with the host cell: viral adsorption to the cellular surface, penetration into the cell, maturation and assembly of virions are discussed. The data on the significance of lipid composition phenotype of the virus and host cell in realization of the viral infection of the cell are reviewed. PMID- 2195323 TI - Distribution of methyl and ethyl adducts following alkylation with monofunctional alkylating agents. AB - Alkylating agents, because of their ability to react directly with DNA either in vitro or in vivo, or following metabolic activation as in the case of the dialkylnitrosamines, have been used extensively in studying the mechanisms of mutagenicity and carcinogenicity. Their occurrence is widespread in the environment and human exposure from natural and pollutant sources is universal. Since most of these chemicals show varying degrees of both carcinogenicity and mutagenicity, and exhibit compound-specific binding patterns, they provide an excellent model for studying molecular dosimetry. Molecular dosimetry defines dose as the number of adducts bound per macromolecule and relates the binding of these adducts to the human mutagenic or carcinogenic response. This review complies DNA alkylation data for both methylating and ethylating agents in a variety of systems and discusses the role these alkylation products plays in molecular mutagenesis. PMID- 2195324 TI - The importance of molecular dosimetry and analysis of mutations for estimation of genetic risk. AB - A method of estimating risk to germ cells is developed by using both molecular dosimetry and analysis of mutations for points of commonality in comparison among test systems. Studies on adduct formation can be related to dose in germ cells of test systems suitable for genetic analysis of mutations through successive generations. To analyze mutations properly, both classical genetic analysis to describe large deletions and chromosomal aberrations along with molecular analysis to describe mutations at the nucleotide level must be used. A complete description of mutations permits comparison with the data that are recently becoming available on spontaneous mutations in humans where the observed change in DNA can be related to a health effect. PMID- 2195325 TI - Review of the molecular characteristics of gene mutations of the germline and somatic cells of the human. AB - Molecular analyses of the limited number of de novo germinal mutations identified in humans indicate that an array of alterations in gene structure can be generated. Similar conclusions are derived from the large data set obtained from molecular analyses of alleles that segregate in the human population and cause genetic diseases. The molecular alterations include nucleotide substitutions as well as insertions, deletions and other rearrangements of the DNA. The lesions may be located in the coding or the noncoding regions of genes or may involve the flanking sequences. The insertions and deletions involve fragments ranging from single nucleotides to many kilobases, and involve both unique sequences and repetitive elements. The nature of the lesions observed to date as either de novo mutations or segregating variants suggests there are locus-specific characteristics of the alterations in DNA structure that are recovered as genetic diseases. Differences in mutation spectra among genetic loci appear to reflect both the structure of the target sequences and the relationship between gene structure and gene function. No induced germinal mutations have been identified, thus no data are available that reveal the relationships between mutagenic exposures and the molecular fingerprints of the lesion induced in the human germ cell and transmitted to the subsequent generations. In contrast, the prospects for analyzing the roles of genetic target, exposure history and individual responsiveness to exposure in creating particular molecular lesions in somatic cells are excellent, both for alterations of single nucleotides and for major alterations of gene structure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2195326 TI - The serial dosing rodent bone-marrow micronucleus assay test protocol: context, purpose and design of the collaborative study. PMID- 2195327 TI - Overview of the study in relation to protocol design for the rodent bone-marrow micronucleus assay. PMID- 2195328 TI - Modification of the kinetochore immunofluorescence staining method for human fibroblasts for use with a commercially available anticentromere antibody. PMID- 2195329 TI - Recent advances in DNA repair. A report of the 1989 meeting of the British Photobiology Society in association with the DNA-Repair Network. PMID- 2195330 TI - Studies on mammalian mutants defective in rejoining double-strand breaks in DNA. AB - Mutants with defects in the rejoining of DNA double-strand breaks (dsbs) have been identified and characterised from E. coli and the yeast, Saccharomyces cerevisiae. More recently, 3 mammalian cell mutants with defective dsb rejoining have also been described. These mutants are xrs, XR-1 and L5178Y/S, and they are derived from at least two distinct complementation groups. The aim of this article is to review the current status of the studies with these mammalian cell mutants which are defective in dsb rejoining and, in particular, to compare their properties with those mutants identified from lower organisms. Possible mechanistic differences in the process of dsb rejoining between prokaryotes and lower and higher eukaryotes are discussed. All the mammalian mutants defective in dsb rejoining, are sensitive primarily to ionising radiation with little cross sensitivity to UV-radiation. This is similar to the rad52 mutants of S. cerevisiae but contrasts to the majority of the E. coli mutants with defective dsb rejoining. Where studied, the mammalian cell mutants show enhanced resistance to ionizing radiation in late S/G2 phase, which, in one case, correlates with an enhanced ability to rejoin dsbs. This, together with other evidence, suggests that two mechanisms of dsb rejoining may exist in higher eukaryotes, one which operates uniquely in S/G2 phase and a second mechanism operating throughout the cell cycle and dependent upon the xrs and XR-1 gene products (although whether the xrs and XR-1 dependent pathways are distinct cannot at present be ascertained). Since duplicate homologues will be present in late S/G2 phase cells, this pathway may involve a recombinational mechanism. The xrs-dependent pathway might involve illegitimate recombination, but the xrs mutants do not appear to have a major defect in homologous recombination (involving plasmid DNA) and in this respect are distinct from rad52 mutants. PMID- 2195331 TI - Mutagenicity, carcinogenicity and teratogenicity of cobalt metal and cobalt compounds. AB - Cobalt metal and cobalt compounds are extensively used for the production of high temperature alloys, diamond tools, cemented carbides and hard metals, for the production of various salts used in electroplating and as catalysts, drying agents in paints, additives in animal feeds and pigments. Cobalt oxides are used not only in the enameling industry and for pigments, but also in catalytic applications. There is no indication that cobalt metal and cobalt compounds constitute a health risk for the general population. Allergic reactions (asthma, contact dermatitis) can be induced by certain cobalt compounds. Interstitial fibrosis has also been observed in workers exposed to high concentrations of dust containing cobalt, tungsten, iron, etc., mainly in the cemented carbides and the diamond-polishing industries. Several experiments have demonstrated that single or repeated injections of cobalt metal powder or some forms of cobalt salt and cobalt oxide may give rise to injection site sarcoma in rats and in rabbits but the human health significance of such data is questionable. Intratracheal administration of a high dose of one type of cobalt oxide induces lung tumors in rats but not in hamsters. In the latter long-term inhalation of cobalt oxide (10 mg/m3) did not increase the incidence of lung cancer. The human data are too limited to assess the potential carcinogenic risk for workers. Co2+ interacts with protein and nucleic acid synthesis and displays only weak mutagenic activity in microorganisms. Some cobalt salts have been reported to enhance morphological transformation of Syrian hamster embryo cells. Cobalt chloride displays some limited mutagenic activity in yeast and some cobalt compounds are able to produce numerical and structural chromosome aberrations in plant cells. Cobalt and its salts appear to be devoid of mutagenic and clastogenic activity in mammalian cells. Cobaltous acetate and cobaltous chloride have not been found to be teratogenic in hamsters and rats respectively. PMID- 2195332 TI - The in vivo micronucleus assay in mammalian bone marrow and peripheral blood. A report of the U.S. Environmental Protection Agency Gene-Tox Program. AB - The protocol recommended for the micronucleus assay in mammalian bone marrow has been revised and simplified. The number of sample times has been reduced to one or two, depending upon the dosing protocol. The minimum number of cells to be scored per treatment group has been increased to 20,000 to increase the ability of the assay to detect a doubling of the control micronucleus frequency. Use of both male and female animals is recommended. Scoring of micronuclei in polychromatic erythrocytes of peripheral blood is included as a variation of the bone marrow assay. Published data on chemicals tested by the micronucleus assay have been reviewed and are summarized. PMID- 2195333 TI - Detection of induced mitotic chromosome loss in Saccharomyces cerevisiae--an interlaboratory assessment of 12 chemicals. AB - Induced mitotic chromosome loss was assayed using diploid yeast strain S. cerevisiae D61.M. The test relies upon the uncovering and expression of multiple recessive markers reflecting the presumptive loss of the chromosome VII homologue carrying the corresponding wild-type alleles. An interlaboratory study was performed in which 12 chemicals were tested under code in 2 laboratories. The results generated by the Berkeley and the Darmstadt laboratories were in close agreement. The solvents benzonitrile and methyl ethyl ketone induced significantly elevated chromosome loss levels. However, a treatment regime that included overnight storage at 0 degree C was required to optimize chromosome loss induction. Hence, these agents are postulated to induce chromosome loss via perturbation of microtubular assembly. Fumaronitrile yielded inconsistent results: induction of chromosome loss and respiratory deficiency was observed in both laboratories, but the response was much more pronounced in the Darmstadt trial than that observed in Berkeley. The mammalian carcinogens, benzene, acrylonitrile, trichloroethylene, 1,1,1-trichloroethane and 1,1,1,2 tetrachloroethane failed to induce chromosome loss but elicited high levels of respiratory deficiency, reflecting anti-mitochondrial activity. Trifluralin, cyclophosphamide monohydrate, diazepam and diethylstilbestrol dipropionate failed to induce any detectable genetic effects. These data suggest that the D61.M system is a reproducible method for detecting induced chromosome loss in yeast. PMID- 2195334 TI - Salmonella mutagenicity and rodent carcinogenicity: quantitative structure activity relationships. AB - Based on a compilation of 222 reports of rodent nominal lifetime carcinogenicity bioassays by the NCI/NTP on the one hand, and corresponding Salmonella mutagenicity bioassays (Ames tests) on the other, Ashby and Tennant (1988) have divided the carcinogens and non-carcinogens into genotoxic (Ames test positive) and non-genotoxic (Ames test negative) groups and discussed structural characteristics common to each of these groups. The Ames test alone was deemed to be adequate for the identification of genotoxicity because other short-term bioassays, and even combinations, or batteries, appeared to offer no significant advantages. From the results of this study it is possible to achieve (1) a division of the carcinogens into the same genotoxic and non-genotoxic groups, and (2) a division of the non-genotoxic compounds into the same carcinogenic and non carcinogenic groups, solely on the basis of structure-activity relationships, with a classification accuracy of approx. 95%. (1) An equation comprising 8 sigma molecular charge descriptors, 2 molecular connectivity indices (MCIs), 2 kappa molecular shape descriptors and one MOLSTAC substructure descriptor achieved discrimination between genotoxic and non-genotoxic carcinogens with an accuracy of 94.5%. (2) Another equation comprising 8 sigma molecular charge descriptors, 3 MCIs, one kappa shape descriptor and 12 substructural descriptors achieved discrimination between non-genotoxic carcinogens and non-genotoxic non carcinogens with an accuracy of 95.2%. These SAR models are suitable for the distinction between (1) genotoxic and non-genotoxic carcinogens and (2) carcinogenic and non-carcinogenic non-genotoxins, both in the absence of animal bioassay data. PMID- 2195335 TI - Mechanism of antimutagenicity of aquatic plant extracts against benzo[a]pyrene in the Salmonella assay. AB - The mechanism of antimutagenicity of water extracts of grass-wrack pondweed (Potamogeton oxyphylus Miquel), curled pondweed (Potamogeton crispus L.) and smartweed (Polygonum hydropiper L.) towards benzo[a]pyrene mutagenicity in Salmonella typhimurium was investigated. The antimutagenic components in the aquatic plants were water-soluble, heat-resistant and had a high molecular weight; chlorophyll did not play an important role. PMID- 2195336 TI - Studies on the potential mutagenicity of p-phenylenediamine in oxidative hair dye mixtures. AB - An aqueous mixture of p-phenylenediamine dihydrochloride, resorcinol and hydrogen peroxide, incubated for 30 min at 37 degrees C, was not mutagenic in the Ames test and in the mouse lymphoma assay and did not produce chromosome aberrations in human lymphocytes, whereas the same mixture without resorcinol was mutagenic in the Ames test and the chromosome aberration assay, probably due to the formation of Bandrowski's base. The formation of mutagenic Bandrowski's base and other reactive products could be demonstrated by thin-layer chromatography and subsequent Ames testing. Preincubation for 0-7 h of 5 different oxidative mixtures of p-phenylenediamine dihydrochloride and various couplers at 37 degrees C resulted in mutagenicities in the Ames test ranging from 'very strong effects' at 0 or 0.5 h for 2,4-diaminoanisole dihydrochloride to 'not mutagenic' at up to 7 h preincubation time for a recently developed alternative coupler. A comparable ranking of mutagenic potencies of the same mixtures could be obtained by Ames tests with dyed buffalo hair strands, either tested directly on the agar plates or by testing the solvent extracts of the colored strands. The optimal combination without any sign of mutagenic tendency was finally tested in a commercially available hair dye formulation. This complex mixture was also not mutagenic in the Ames test. Our main conclusions are as follows. (I) Oxidative hair dye mixtures of p-phenylenediamine dihydrochloride and non-mutagenic couplers are not mutagenic if tested under normal conditions of use; the formation of mutagenic reaction products (such as Bandrowski's base) can be prevented if the oxidative reaction time is limited to 30 min and if about equimolar proportions of para to meta compounds are used. (II) Optimal non mutagenic combinations of primary intermediates (such as p-phenylenediamine dihydrochloride) and couplers can be evaluated in the Ames test by either time dependent preincubation of the mixtures or the described test protocol with hair strands. PMID- 2195337 TI - An oxygen dependence in chromium mutagenesis. AB - Evidence is provided that mutagenicity in Salmonella by a chromium(VI) salt and a chromium(III) compound has a differential dependence on the presence of oxygen. The mutagenic chromium(III) compound, cis-dichlorobis(2,2' bipyridyl)chromium(III), reverted Salmonella strains, TA102 and TA2638, only under aerobic conditions. Potassium dichromate (chromium VI) required the presence of oxygen to revert the Salmonella strain TA102 but induced a moderate reversion frequency in TA2638 under anaerobic conditions. The data also support a role for oxygen radicals in chromium-mediated mutagenesis and suggests at least two pathways by which chromium compounds can induce mutations. PMID- 2195338 TI - Use of electrophysiologic tests to measure disease progression in ALS therapeutic trials. AB - A battery of electrophysiologic tests was developed to assess the relative degree of lower and upper motor neuron (spasticity) deficit in a group of ALS patients enrolled in a therapeutic trial. Test results were correlated with strength in the tibialis anterior muscle as determined by measurement of maximum voluntary isometric contraction (MVIC), using strain gauge tensiometers, and were also correlated with a clinical spasticity rating scale. Patients were tested every 6 to 8 weeks over more than 1 year. Compound muscle action potential amplitude (CMAPa) from tibialis anterior correlated best with MVIC and also showed a strong linear correlation with time, as did MVIC. Other tests correlated poorly with MVIC on the average, although individual patients did show high correlations. In those patients where correlation between CMAPa and MVIC was low, MVIC did not show a high linear correlation with time and was also highly variable. This study suggests that the addition of CMAPa should be considered in ALS therapeutic trials if MVIC is not available. In addition, CMAPa can be useful in study samples where MVIC deterioration is not linear over time or is highly variable. PMID- 2195339 TI - Immunocytochemical study of dystrophin at the myotendinous junction. AB - Dystrophin is the protein whose deficiency results in Duchenne muscular dystrophy. The protein has homologies with a number of cytoskeletal proteins, is localized at the muscle sarcolemma and it may provide stability to the muscle plasma membrane. Using immunocytochemical techniques, we have studied dystrophin localization at the myotendinous junction, a region of membrane complexity that requires more stability because it is subjected to great mechanical stress during the transmission of contractile force to the tendon. The results showed subsarcolemmal deposits of dystrophin at the junctional folds of the myotendon as well as membrane-associated dystrophin at extrajunctional sarcolemma. The findings suggest that dystrophin may be one of the components linking terminal actin filaments to the subplasmalemmal surface of the junctional folds of the myotendon. PMID- 2195340 TI - Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. AB - BACKGROUND AND METHODS: Although cachexia often accompanies advanced heart failure, little is known about the causes of the cachectic state. To assess the potential role of tumor necrosis factor in the pathogenesis of cardiac cachexia, we measured serum levels of the factor in 33 patients with chronic heart failure, 33 age-matched healthy controls, and 9 patients with chronic renal failure. RESULTS: Mean (+/- SEM) serum levels of tumor necrosis factor were higher in the patients with heart failure (115 +/- 25 U per milliliter) than in the healthy controls (9 +/- 3 U per milliliter; P less than 0.001). Nineteen of the patients with chronic heart failure had serum levels of tumor necrosis factor greater than or equal to 39 U per milliliter (greater than 2 SD above the mean value for the control group), whereas the remaining 14 patients had serum levels of tumor necrosis factor below this level. The patients with high levels of tumor necrosis factor were more cachectic than those with low levels (82 +/- 3 vs. 95 +/- 6 percent of ideal body weight, respectively; P less than 0.05) and had more advanced heart failure, as evidenced by their higher values for plasma renin activity (2.92 +/- 0.53 vs. 1.06 +/- 0.53 ng per liter per second [10.5 +/- 1.9 vs. 3.8 +/- 1.9 ng per milliliter per hour]; P less than 0.01) and lower serum sodium concentration (135 +/- 1 vs. 138 +/- 1 mmol per liter; P less than 0.05). The group with high levels of tumor necrosis factor also had lower hemoglobin levels (7.82 +/- 0.2 vs. 8.69 +/- 0.4 mmol per liter [12.6 +/- 0.4 vs. 14.0 +/- 0.6 g per deciliter]) and higher values for blood urea nitrogen (19.5 +/- 2.2 vs. 12.5 +/- 1.8 mmol per liter) than the group with low levels of tumor necrosis factor (P less than 0.05 for both). The high levels of tumor necrosis factor were not due solely to decreased renal clearance, however, since the levels in the patients with heart failure were considerably higher than those in the nine patients with chronic renal failure (115 +/- 25 vs. 45 +/- 25 U per milliliter; P less than 0.05). CONCLUSIONS: These findings indicate that circulating levels of tumor necrosis factor are increased in cachectic patients with chronic heart failure and that this elevation is associated with the marked activation of the renin-angiotensin system seen in patients with end-stage cardiac disease. PMID- 2195341 TI - Viral encephalitis. PMID- 2195342 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 30-1990. A 47-year-old man with a rash, fever, and headaches. PMID- 2195343 TI - Quality assurance in Medicare. PMID- 2195344 TI - The carriage of Escherichia coli resistant to antimicrobial agents by healthy children in Boston, in Caracas, Venezuela, and in Qin Pu, China. AB - BACKGROUND AND METHODS: The healthy members of a community represent its largest reservoir of bacteria resistant to antimicrobial agents. We compared the resistance to eight agents of Escherichia coli in stool samples from untreated, healthy children in cities on three continents. RESULTS: When screened by a selective method that detected 1 resistant colony in 10,000 colonies, nearly half the children in Boston (18 of 39) had no resistant colonies--a finding consistent with the findings of other surveys performed in developed countries. However, all but 1 of 41 children screened in Caracas, Venezuela, and all but 2 of 53 in Qin Pu, China, carried resistant strains. Only 1 child in Boston but 25 in Caracas and 34 in Qin Pu carried strains resistant to trimethoprim. None of the children in Boston or Caracas but 17 in Qin Pu carried strains resistant to gentamicin. Among 10 colonies selected randomly from each stool sample, the average frequency of resistance in Caracas was 3.6 times greater than in Boston, and that in Qin Pu was 5.3 times greater. There was resistance to five or more antimicrobial agents in 20 percent of the Qin Pu strains and in 6 percent of the Caracas strains but in none of the Boston strains. CONCLUSIONS: In addition to clinical isolates, as reported previously, the bacteria that colonize health children in the community may be resistant far more often in some regions than in others. A low rate of carriage of antimicrobial resistance in the community should become a public health goal. PMID- 2195345 TI - Effect of topical cyclosporine rinse on oral lichen planus. A double-blind analysis. AB - BACKGROUND: Oral lichen planus is a relatively common disorder of the mouth that can be debilitating. It is frequently palliated with topical or systemic corticosteroids and retinoids. These treatments require prolonged use, however, and are not always effective. METHODS: In a double-blind trial, 16 patients with symptomatic oral lichen planus were randomly assigned to receive either topical cyclosporine or its vehicle. The patients swished and expectorated 5 ml of medication (containing 100 mg of cyclosporine per milliliter) three times daily. RESULTS: After eight weeks, the eight recipients of cyclosporine had marked improvement in erythema (P = 0.003), erosion (P = 0.02), reticulation (presence of white lacelike lesions; P = 0.007), and pain (P = 0.002), whereas the eight recipients of vehicle had no change or minimal improvement. After a switch to cyclosporine for eight weeks, the vehicle-treated patients had improvement similar to that seen in the patients who initially received cyclosporine. There were no systemic side effects. In most cases blood cyclosporine levels were low or undertectable. Cyclosporine levels present in specimens of oral mucosa at the end of therapy four hours after the patients swished were similar to the levels previously reported in psoriatic lesions after treatment with systemic cyclosporine (14 mg per kilogram of body weight per day). CONCLUSIONS: As a topical preparation, cyclosporine may be useful in the treatment of oral lichen planus and possibly other cutaneous disorders. PMID- 2195346 TI - A randomized, controlled trial of interferon alfa-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. The Hepatitis Interventional Therapy Group. AB - BACKGROUND AND METHODS: Chronic hepatitis B is a common and often progressive liver disorder for which there is no accepted therapy. To assess the efficacy of treatment with interferon, we randomly assigned patients with chronic hepatitis B to one of the following regimens: prednisone for 6 weeks followed by 5 million units of recombinant interferon alfa-2b daily for 16 weeks; placebo followed by 5 million units of interferon daily for 16 weeks; placebo followed by 1 million units of interferon daily for 16 weeks; or observation with no treatment. RESULTS: Hepatitis B e antigen and hepatitis B viral DNA disappeared from serum significantly more often in the patients given prednisone plus interferon (16 of 44 patients, or 36 percent) or 5 million units of interferon alone (15 of 41; 37 percent) than in the untreated controls (3 of 43; 7 percent; P less than 0.001); the difference between those given 1 million units of interferon (7 of 41; 17 percent) and the controls was not significant. The strongest independent predictor of a response to treatment was the amount of hepatitis B viral DNA in serum at entry (P less than 0.0001). Of the 38 patients who responded to interferon, 33 (87 percent) had normal serum aminotransferase levels after therapy; 11 patients who responded (29 percent), but no controls, lost the hepatitis B surface antigen. Blinded histologic assessment revealed a significant improvement in periportal necrosis in the treated patients (P = 0.03). CONCLUSIONS: In chronic hepatitis B, treatment with interferon alfa-2b (5 million units per day for 16 weeks) was effective in inducing a sustained loss of viral replication and achieving remission, assessed biochemically and histologically, in over a third of patients. Moreover, in about 10 percent of the patients treated with interferon, hepatitis B surface antigen disappeared from serum. PMID- 2195348 TI - Starting life resistance-free. PMID- 2195347 TI - Transplacental passage of insulin in pregnant women with insulin-dependent diabetes mellitus. Its role in fetal macrosomia. AB - BACKGROUND AND METHODS: Fetal macrosomia occurs despite nearly normal maternal blood glucose levels in women with diabetes treated with insulin. We examined the hypothesis that it may be caused by insulin transferred as an insulin-antibody complex from the mother to her fetus. We adapted and validated a method based on high-performance liquid chromatography and used it to quantitate insulin in small volumes (0.5 to 1.0 ml) of cord serum from 51 infants born to mothers with insulin-dependent diabetes mellitus. RESULTS: In mothers receiving only human insulin (n = 6), only human insulin was detected in cord serum. Of the remaining 45 infants, whose mothers received animal insulin during pregnancy, 28 (group 1) had levels of animal (bovine or porcine) insulin (mean [+/- SE], 707 +/- 163 pmol per liter) that constituted 27.4 +/- 2.5 percent of the total insulin concentration (2393 +/- 500 pmol per liter) measured in the cord serum. The cord serum insulin concentration in the remaining 17 infants (group 2), in whom only human insulin was detected (381 +/- 56 pmol per liter), was only 15 percent of that in group 1 (P less than 0.001). There was a significant correlation between the maternal and the cord-serum concentrations of anti-insulin antibody and the concentration of animal insulin in the baby (r = 0.77, P less than 0.01, and r = 0.76, P less than 0.001, respectively), suggesting that the animal insulin was transferred as an insulin-antibody complex. In group 1 the mean concentration of animal insulin in cord serum was higher in the 12 infants with macrosomia than in the 16 infants without the condition (1113 +/- 321 vs. 402 +/- 110 pmol per liter; P less than 0.05), and the concentration of animal insulin in cord serum correlated with birth weight (r = 0.39, P less than 0.05). The maternal glycosylated hemoglobin values and the incidence of respiratory distress syndrome were similar in groups 1 and 2. CONCLUSIONS: Considerable amounts of antibody bound insulin are transferred from mother to fetus during pregnancy in some women with insulin-dependent diabetes mellitus; the extent of transfer correlates with the maternal concentration of anti-insulin antibody. The correlation between macrosomia and the concentrations of animal insulin in cord serum indicates that the transferred insulin has biologic activity and suggests that the formation of antibody to insulin in the mother is a determinant of fetal outcome independent of maternal blood glucose levels. PMID- 2195349 TI - Hyperinsulinemia and macrosomia. PMID- 2195350 TI - Inhibition of glucose transport by immunoglobulins in type I diabetes mellitus. PMID- 2195351 TI - Recombinagenicity of caffeine for Candida albicans. AB - Caffeine at concentrations of 0.5 x 10(-2) M or higher inhibited cell replication and induced gene segregations in Candida albicans cultured on defined complete medium. Both responses increased incrementally with increasing caffeine concentrations, and were more severe during incubation at 37 degrees C than 25 degrees C; at 37 degrees C, caffeine levels above 1.5 x 10(-2) M caused cellular inactivation. Caffeine effects occurred only under conditions permitting cell growth, and their magnitudes were greater for unbudded than budding cells, were influenced by cellular genetic backgrounds, and were unaffected by the presence of adenine in the medium. Evaluations of segregations for recessive auxotrophic markers of a four member linkage group carried heterozygously in a cis arrangement in treated cells established that induced segregants arise through either reciprocal or nonreciprocal recombinations. The frequency distributions of classes of reciprocal and nonreciprocal recombinants for these markers conformed with those previously obtained following induction by ultraviolet radiation, indicating that the probabilities of recombinational events within the chromosomal regions defined by the markers are not biased by the differences in kinds of initial DNA lesions caused by the two recombinagens. A panel of four protoplast fusion hybrids considered deficient for DNA repair because of enhanced susceptibilities to UV induced cellular inactivation and mitotic recombination exhibited corresponding increased sensitivities to caffeine, signifying that DNA damage induced by caffeine is subject to repair. Caffeine did not affect behavior of a variant strain exhibiting high frequency phenotypic switching between minute smooth and large rough colonial forms, and no evidence for mutagenicity of the drug was obtained with systems for detection of forward or reverse mutations. The mechanism of caffeine's recombinagenicity, and the implications of that property for genetic studies of C. albicans are discussed. PMID- 2195352 TI - Evolution. Mountaineering with microbes. PMID- 2195353 TI - Rapid evolution in response to high-temperature selection. AB - Temperature is an important environmental factor affecting all organisms, and there is ample evidence from comparative physiology that species and even conspecific populations can adapt genetically to different temperature regimes. But the effect of these adaptations on fitness and the rapidity of their evolution is unknown, as is the extent to which they depend on pre-existing genetic variation rather than new mutations. We have begun a study of the evolutionary adaptation of Escherichia coli to different temperature regimes, taking advantage of the large population sizes and short generation times in experiments on this bacterial species. We report significant improvement in temperature-specific fitness of lines maintained at 42 degrees C for 200 generations (about one month). These changes in fitness are due to selection on de novo mutations and show that some biological systems can evolve rapidly in response to changes in environmental factors such as temperature. PMID- 2195354 TI - Visual neuroscience. A causal chain in motion. PMID- 2195356 TI - How did AIDS begin? PMID- 2195355 TI - Role of abortive retroviral infection of neurons in spongiform CNS degeneration. AB - Retroviruses are involved in several human neurological diseases with varying pathological features. Whether these diseases are due to a direct effect of the virus on nervous system cells is unknown. To gain insight into the pathogenesis of one retroviral neurological disease, we are studying the murine neurotropic retrovirus, Cas-Br-E, which causes lower motor neuron disease associated with spongiform degenerative changes in brain and spinal cord. Central nervous system (CNS) injury seems to be due to direct viral action, but the precise target cells of the virus are uncertain. After blood-borne virus enters the CNS it is found in capillary endothelial cells. No microscopic evidence for virus within glia or neurons has been found in some studies, whereas virus or incomplete particles have been observed in CNS cells in other studies. Here we identify the neuron as a major target for Cas-Br-E in the CNS, suggesting that this disease may be a direct result of viral infection of neurons. We also show that envelope protein (Env, encoded by the env gene), a major determinant of neurovirulence, cannot be detected in neurons but is present in non-neuronal cells, although spliced env messenger RNA is synthesized in CNS tissue. This suggests that a post transcriptional step in Cas-Br-E Env protein synthesis is impaired and that the neurological disease may be a consequence of abortive replication of virus in neurons. This may explain the failure to find neuronal infection in other neurological diseases by conventional methods of virus detection. PMID- 2195357 TI - A case of acute renal failure induced by the co-administration of NSAIDs and captopril. PMID- 2195358 TI - [Serine protease inhibitors (serpins); regulators of coagulation and inflammation reactions with therapeutic potential]. PMID- 2195359 TI - [The patient's functional status; clinimetrics in family practice]. PMID- 2195360 TI - [Clinical significance of selective decontamination in patients in the intensive care unit]. PMID- 2195361 TI - [Surgical treatment of massive pulmonary embolism]. AB - Between 1975 en 1988, 16 patients underwent pulmonary embolectomy because of massive pulmonary embolism. Three of these patients, in whom shock and cardiac arrest had occurred prior to operation, died. The role of surgery in the treatment of massive pulmonary embolism is a topical issue, also in view of the rise of thrombolytic therapy and its acceptable results. For patients whose haemodynamic condition deteriorates in spite of thrombolytic treatment and for patients in whom thrombolytic therapy is contraindicated, pulmonary embolectomy remains an effective form of treatment. PMID- 2195362 TI - [Consensus about consensus. A critical consideration of the procedure of the CBO consensus development (Central Support Organ for Peer Review)]. PMID- 2195363 TI - Familial pancreatic cancer (Part II): Surveillance, diagnostic tests, and surgical strategies. AB - We have provided a description of the current state of knowledge relevant to familial/hereditary pancreatic cancer. Since the most important clinical ramifications of this disease, whose incidence and mortality are essentially the same, rests upon its earlier detection, we have also characterized available diagnostic tests, surgical strategies, and current knowledge about its pathology. We believe that advances in control of pancreatic cancer will be heavily impacted by progress in the search for new and better diagnostic tests. These could include monoclonal antibodies targeted to pancreatic tumor tissue, and possibly pancreatic site-specific P450's, as well as biomolecular/genetic techniques, particularly when focused on individuals at high risk. Thus, family studies are important in this disease because if an autosomal dominantly inherited form of pancreatic cancer is delineated, one could identify individuals at high risk early in life. Comparison could then be made with individuals in branches of the family where the disease is not segregating. Thus, there would be a greater potential for discovery of methods for early detection with evaluation of sensitivity and specificity in families wherein the predictability for pancreatic cancer occurrence is high. PMID- 2195364 TI - Ultrasound in congenital hip disease. Part 1--Review of technique. PMID- 2195365 TI - Ultrasound in congenital hip disease. Part II--Prospective study. PMID- 2195366 TI - Of a probe. PMID- 2195367 TI - Retiree is advocate for the elderly. Interview by Rogene Calvet. PMID- 2195368 TI - [Preventive goals in the treatment of the mutilated dentition]. AB - It can be expected that the percentage of edentulous people wil decrease in the coming decades as a result of an improved oral health, whereas the number of edentulous people will increase as a result of the strong increase of the ageing population. If the preservation of the natural dentition is no longer possible, the remaining teeth of a mutilated dentition have to be extracted according to some specific principles. But also the aftercare of the edentulous patient has to be extended according to some specific guidelines, within the framework of the so called 'preventive-prosthetic-treatment-strategy'. Preservation of the alveolar process is the main goal in both cases. PMID- 2195369 TI - [Intraspinal paraganglioma. Apropos of 3 cases with a review of the literature]. AB - The authors present three cases of paraganglioma located in the cauda equina. In all cases pre-operative diagnosis was neurinoma of the cauda equina and only the histology permitted correct identification. All were intradural extramedullary tumors and in two cases the presenting and dominant symptom was low back pain and sciatica. The remaining third case experimented a paraparesis with urinary and fecal incontinence. The follow-up (range of 4 months-4 years) after total excision was uneventful in two cases and showed in the third case with preoperative paraparesis, some persistent urinary incontinence (follow-up: 3 years) with good motor recovery. The light microscopic features were a Zellballen pattern of cells containing argyrophil granules. Electron microscopy was not performed. The most likely theory regarding the embryogenesis of cauda equina paragangliomas is that they arise from pre-existing paraganglia, possibly of the visceral-autonomic group. The prognosis after complete excision appears to be good. The literature is thoroughly reviewed. PMID- 2195370 TI - [Colloid cysts of the third cerebral ventricle. Computed x-ray tomography, MRI and stereotaxic puncture. Apropos of 9 cases]. AB - The authors report their experience with Colloid Cysts of the third ventricle (9 cases treated between 1983 and 1989). Eight of them were punctured using stereotactic approach; five cysts were completely evacuated and the patients are free of recurrence. In three cases, tapping was impossible or the cyst insufficiently evacuated and the patients were secondary operated on (open microsurgical approach). The last case was directly operated on. Colloid cysts cured by stereotactic puncture were all hypo or iso-dense at C.T. scan and had a diameter of more than 1 cm. All these cases have had a M.R.I. exploration and the image of the cyst was always the same increased T1 and T2 signal. Unfortunately, we did not have the opportunity to realize M.R.I. in colloid cysts of a small size and hyperdense at C.T. scan. These results can help to the indication of a stereotactic puncture at the first attempt in some well defined colloid cysts. PMID- 2195371 TI - [Cerebral aspergillotic granuloma. Apropos of a case and a review of the literature]. AB - The authors report a case of aspergillus granuloma of the brain, in a 28 year old woman, simulating a meningioma. Preoperative diagnosis of aspergilloma is difficult. However, it may be suspected in a patient who has associated pulmonary and paranasal sinus fungal infection. Peroperatively it may be confused with a brain tumour. The lesions usually are in the frontal lobes. Diagnosis can be made only by surgical biopsy with identification of fungal elements. Granuloma induce a good host response, and a high capacity to elaborate antibodies. PMID- 2195372 TI - [Extracranial aneurysm of the posterior inferior cerebellar artery. A case report]. AB - A case is presented of an aneurysm arising in an extracranial loop of the left posterior inferior cerebellar artery (P.I.C.A.). Two similar cases can be found in a review of the literature. It is essential to obtain clear visualization of both P.I.C.A.s. in the evaluation of patients with subarachnoid hemorrhage. Surgical treatment of this aneurysm, located distal to the lateral medullary segment, involves a midline approach with retraction or subpial resection of the tonsillar tip. PMID- 2195373 TI - [A century of neurotransplantation in mammals]. AB - The transplantation of neural tissue into the mammalian brain has been studied for a century. Although the experimental foundations of neurotransplantation were limited to basic biological issues, the progress made over the last decade in the use of foetal neurotransplants to replace interrupted neuronal pathways or to correct induced functional deficit of the central nervous system (C.N.S.), has opened a new field of research for repair of the damaged C.N.S. This review summarizes three major topics: (1) the major developments in the field of neurotransplantation since the first attempt in 1890, (2) the global field of application of grafting techniques of autologous, homologous and heterologous transplants to particular neuroaxonal systems in animal models (sensory, endocrine, motor, cognitive systems), (3) the specific applications of neurotransplantation to experimental forms of human neurological disorders in rodents and non human primates as a potential treatment for neurodegenerative diseases, and the future directions of neural grafting techniques (in vitro and transgenic techniques, artificial substrates) in the context of the scientific and the ethical problems which have been recently addressed. PMID- 2195374 TI - The effect of castanospermine on the synthesis of synaptic glycoproteins by rat brain slices. AB - Slices were prepared from rat forebrains and the incorporation of [3H]mannose and [35S]methionine into proteins and glycoproteins determined. The incorporation of methionine continued to increase for up to 8 hours whereas mannose incorporation was maximal between 2 and 4 hours and declined thereafter. Glycopeptides prepared by pronase digestion of [3H]mannose-labeled glycoproteins were digested with endoglucosaminidase H (endo H) and analysed by gel filtration. The major endo H sensitive oligosaccharide eluted in a position similar to standard Man8GlcNAc. In the presence of castanospermine, which inhibits glucosidase I, the first enzymatic step in the processing of N-linked oligosaccharides, a new endo H sensitive glycan similar in size to standard Glc3Man9GlcNAc2 accumulated. Synaptic membranes (SMs) were isolated from slices which had been incubated with either [3H]mannose or [35S]methionine in the presence and absence of castanospermine. In the presence of inhibitor the relative incorporation of [3H]mannose into high-mannose glycans of synaptic glycoproteins was increased. The incorporation of newly synthesized, [35S] methionine-labeled, Con A-binding glycoproteins into SMs was not affected by the addition of inhibitor. Many of the glycoproteins synthesized in the presence of castanospermine exhibited a decreased electrophoretic mobility indicative of the presence of altered oligosaccharide chains. The results indicate that changes in oligosaccharide composition produced by castanospermine had little effect on the subsequent transport and incorporation of glycoproteins into synaptic membranes. PMID- 2195375 TI - Effects of phorbol ester on immunoreactive protein kinase C, insulin binding, and glucose uptake in astrocytic glial and neuronal cells from the brain. AB - Phorbol esters, potent stimulators of protein kinase C (PKC), stimulate [3H]2 deoxy-D-glucose (dGlc) uptake and [125I] insulin binding in cultured glial cells but not neuronal cells from neonatal rat brains. Using an antibody to the alpha and beta forms of PKC we have demonstrated that both neuronal and glial cells contain an immunoactive PKC of Mr approximately 80 kD, although the PKC level in neurons is greater than 4-fold that in glia. The majority of immunoactive PKC (63%) is cytosolic in glial cells although the reverse is true in neuronal cells, in which 88% of the PKC is membrane-bound in the basal state. The most potent phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), stimulates a redistribution of this enzyme in neuronal and glial cells. The TPA-stimulated translocation of PKC from cytosol to membrane precedes TPA's effects on [3H]dGlc uptake and insulin binding in glial cells. PMID- 2195377 TI - Medial septal neurons containing N-acetyl-aspartyl-glutamate-like immunoreactivity project to the hippocampal formation in the rat. AB - We have examined the distribution of N-acetyl-aspartyl-glutamate (NAAG)-like immunoreactive cell bodies in the medial septal nucleus and the nucleus of the diagonal band of Broca of the rat and assessed the involvement of these cells in the septo-hippocampal pathway. A series of experiments was carried out using immunohistochemistry alone or combined with the retrograde transport of a protein gold complex injected into the dorsal hippocampal formation. A large number of NAAG-positive cells was observed in the medial septum and the diagonal band. Quantitative analysis revealed that 26% of the NAAG-like immunoreactive cells in the medial septum project to the dorsal hippocampal formation. These results demonstrate that the dipeptide NAAG is a major component of the rat septo hippocampal pathway. PMID- 2195378 TI - Grace under pressure. The first women to join the county medical societies of New Jersey. PMID- 2195376 TI - Molecular mechanisms of neuronal plasticity during learning: the role of secondary messengers. AB - We present published data along with our own results concerning the role of second messengers and their intracellular receptors in molecular mechanisms associated with the plasticity of neurons during learning. The participation of cyclic 3',5'-adenosine monophosphate, cyclic 3',5'-guanosine monophosphate, calcium, calmodulin, and also the metabolic products of inositol phospholipids, inositol-1,4,5-triphosphate, diacylglycerol and the protein kinase C activated by it, arachidonic acid, and the products of its lipoxygenase oxidation during the regulation of neuronal plasticity over the course of prolonged potentiation, sensitization, habituation, and classical associative training are discussed. PMID- 2195379 TI - Rebecca Hallowell. Atlantic County. PMID- 2195380 TI - Caroline Van Horne. Bergen County. PMID- 2195381 TI - Emma Weeks. Burlington County. PMID- 2195382 TI - Sophia Presley. Camden County. PMID- 2195383 TI - Anna Hand. Cape May County. PMID- 2195384 TI - Mary Dunlap. Cumberland County. PMID- 2195385 TI - Eleanor Haines. Essex County. PMID- 2195386 TI - Ruth Clement. Gloucester County. PMID- 2195387 TI - Florence De Hart. Hudson County. PMID- 2195388 TI - Alice Clark. Hunterdon County. PMID- 2195389 TI - Caroline Marsh. Middlesex County. PMID- 2195390 TI - S. Mabel Grier. Mercer County. PMID- 2195391 TI - Sarah Mackintosh. Monmouth County. Passaic County. PMID- 2195393 TI - Marie Chard. Ocean County. PMID- 2195392 TI - Emma Clark. Morris County. PMID- 2195394 TI - Ellen Smith. Salem County. PMID- 2195395 TI - Mary Gaston. Somerset County. PMID- 2195396 TI - Katherine Stewart. Sussex County. PMID- 2195397 TI - Eleanor Galt. Union County. PMID- 2195398 TI - Doreen Sheffield. Warren County. PMID- 2195400 TI - Transient ischemic attacks: clinical features, pathophysiology and management. AB - A transient ischemic attack (TIA) is a symptom of underlying vascular disease that requires prompt, accurate diagnosis to prevent its possible complications of stroke, myocardial infarction or death. This article presents the clinical features, pathophysiology, clinical course and management of TIAs. Study of the pathophysiology includes a review of normal physiology of the cerebral vascular system, as well as age-related physiologic changes that put the elderly at increased risk for TIAs. The management plan presented includes reduction of risk factors, patient education, physician referral, and medical and/or surgical treatment. Controversies over medical and surgical treatment are briefly examined. PMID- 2195399 TI - The cocaine epidemic: a comprehensive review of use, abuse and dependence. AB - Surveys from the National Institute on Drug Abuse found that the number of people who had tried cocaine at least once increased from 5.4 million in 1974 to 25 million in 1985. Current use, defined as use in the past 30 days, rose from 1.6 million in 1977 to 6 million in 1985. By 1985, 3 million Americans were dependent on cocaine. The re-emergence of cocaine as an epidemic drug of abuse and dependence is a painful reminder of the cocaine epidemic present in the United States at the turn of the century. This time, however, health care providers are challenged with intricate assessment problems. These are proving problematic in their possible solutions, due to the wide spectrum of consequences, the chronicity of the disease and the necessary lifelong commitment to recovery. This article describes the cocaine epidemic by surveying the effects of its use, abuse and dependence. Because this disorder is multidimensional, the health care provider must examine the physical, psychological, family/social, personal and spiritual domains of health. Viewing cocaine addiction in this way provides an accurate appraisal of cocaine's destructiveness for individuals, the family system and society as a whole. PMID- 2195401 TI - Computers in nursing. Why bother with computers? PMID- 2195402 TI - Technology and the CPN. PMID- 2195403 TI - The quest for normoglycaemia: is it worth the effort? PMID- 2195404 TI - Software guide. PMID- 2195405 TI - Ectopic pregnancy: a review of incidence, etiology and diagnostic aspects. PMID- 2195407 TI - New concepts of amniotic fluid embolism: a review. PMID- 2195406 TI - Cocaine: maternal use during pregnancy and its effect on the mother, the fetus, and the infant. AB - Cocaine was previously regarded as a soft drug causing only mild damage. Its use during pregnancy, however, creates a variety of grave medical problems which necessitate immediate attention not only on the part of internists and psychiatrists but also, and more particularly, by obstetricians and pediatricians. The pregnancy of a cocaine-using woman must be carefully managed and regarded as a high-risk one. This in view of the numerous obstetric risks caused by the drug, notably premature separation of the placenta, increased incidence of stillbirths, congenital malformations, premature births, and intrauterine growth retardation. The neonatal monitoring must be focused on prevention of complications resulting from the withdrawal syndrome and associated conditions such as pneumonia, severe weight loss, and contagion from the mother. Moreover, efforts must be made to ensure a strict observation of the infant outside the hospital in view of the far greater incidence of idiopathic infant death in such cases. Owing to the sharp rise of the regular and occasional use of the drug and since pregnant women tend on anamnesis to deny any drug taking, we recommend a test of maternal urine for cocaine and other drugs whenever a suspicion to this effect arises. It is also advisable to test for the presence of such drugs in the urine of the neonate in cases of reasonable suspicion of maternal use during pregnancy, though a negative outcome of the urine test naturally does not rule out a possible use. Strict monitoring of positive cases, accompanied by preventive treatment, may contribute a great deal toward a reduction of perinatal morbidity and mortality associated with cocaine use use. PMID- 2195408 TI - Cervical ectopic pregnancy: review of the literature and report of a case treated by single-dose methotrexate therapy. AB - Methotrexate with folinic acid rescue was used to terminate a clinically diagnosed cervical pregnancy while preserving reproductive capability in a young female patient. The chemotherapy was well tolerated except for transient elevation of liver enzymes. Beta HCG titers fell rapidly and became negative by 13 days. This is the first report showing successful treatment of a cervical pregnancy with single-dose chemotherapy. The literature is reviewed and discussed. PMID- 2195409 TI - The safety and efficacy of tocolytic agents for the treatment of preterm labor. AB - Pharmacologic inhibition of uterine contractions remains the mainstay of treatment for preterm labor despite the ongoing controversy regarding its effectiveness. A diverse variety of tocolytic medications have been proposed for clinical use, with betamimetics and magnesium sulfate being the common therapeutic agents of choice in the United States today. The clinician using these agents should be aware of the significant maternal and fetal side-effects associated with these particular medications. New classes of pharmacologic agents, including prostaglandin synthetase inhibitors, calcium channel blockers and phosphodiesterase inhibitors, have been proposed as tocolytic agents and are currently undergoing critical clinical evaluation. The purpose of this review is to provide a compilation of the available clinical studies that document the safety and efficacy of these various tocolytic agents. PMID- 2195410 TI - Opioid, catecholamine, and steroid interaction in prolactin and gonadotropin regulation. PMID- 2195411 TI - The orphan trains. PMID- 2195412 TI - Phase II clinical evaluation of etoposide (VP-16-213, Vepesid) as a second-line treatment in ovarian cancer. Results of the South-East European Oncology Group (SEEOG) Study. AB - The objective of this trial was to define the antitumor activity and toxicity of etoposide for second-line treatment of patients with bulky ovarian carcinoma. Between February 1, 1986 and November 1, 1988 we recruited 82 patients. Out of them 77 (93.9%) were evaluable for toxicity and 71 (86.6%) for response. Patient characteristics are as follows: median age 57 years (range 15-75), median performance status: WHO 1, prior chemotherapy with more than 3 drugs 24 patients, with previous cisplatin 63 patients, with previous adriamycin 47 patients, with previous irradiation plus chemotherapy 17 patients. The following treatment schedule was applied: each patient started with 150 mg/m2 of etoposide administered i.v. on days 1-3. If this first cycle was well tolerated the dosage was escalated to 200 mg/m2 days 1-3. This higher dosage was then repeated at 4 week intervals. For evaluation of response the WHO criteria were used. One patient (1.4%) achieved complete remission and 5 (7.0%) partial remission. In 48 patients (67.6%) minor response or stabilisation of the disease were observed. Seventeen patients (24%) showed no response. The median duration of remission was 5.5 months (range 2-20). The median duration of stabilisation was 3 months (range 2-24). The median survival time was 10 months with a range of 2-30 months. The myelotoxic side-effects are as follows: WBC less than 2,000 was recorded in 6 patients and greater than 1,000 in 2 patients. Thrombocytopaenia with platelet count less than 50,000 occurred in 1 patient. 26 patients had anaemia WHO grades 2 and 3. Non-haematological toxicity consisted of nausea and vomiting (WHO grade 2:20 patients and grade 3:2 patients), alopecia (WHO grades 2-3:14 and 24 patients, respectively). Though the remission rate in this trial was low, the 10 month median survival with an acceptable quality of life can be taken as a fairly good salvage therapy result. PMID- 2195413 TI - Preoperative immunocytochemical analysis of the estradiol receptor in nonpalpable human breast tumors. AB - An immunocytochemical technique employing a monoclonal antibody to the estrogen receptor was used to analyze the receptor content in tumor biopsy material from nonpalpable breast carcinomas. Fine needle biopsies were obtained from 12 such tumors using a stereotaxic biopsy technique. The smears were used for cytomorphological diagnosis and receptor analysis. The results show that estrogen receptor status can be determined preoperatively in nonpalpable human breast tumors. PMID- 2195414 TI - A case of severe post-radiation caries. PMID- 2195415 TI - The graying of America: optometric considerations. Introduction. AB - Normal and abnormal effects of aging impact greatly on individuals and their families. Health care providers must therefore be knowledgeable about how to care for elderly persons. In order to interact among elderly persons and within the aging network, optometrists need to have a broad understanding of gerontology. PMID- 2195416 TI - Serving the needs of older patients through private practice settings. AB - Current trends dictate that optometric practices will provide eye care for increasingly larger numbers of older patients throughout the foreseeable future. Trends such as demographics, optometric participation in third party plans, and expanding scope of optometric practice exert collective influence in this area of clinical care. Special skills and techniques are needed when caring for these patients, and private practitioners need to integrate newly available information and instrumentation with their existing clinical skills in order to provide optimal care. PMID- 2195417 TI - Low vision and aging. AB - As people age they are more susceptible to various problems in the visual system. The optometrist is in the position to take care of many of the functional losses that result from age-related problems and diseases. With increased awareness of basic low vision and rehabilitation services, the practitioner can continue to care for the visual needs of the older patient. PMID- 2195418 TI - Optometric care of the homebound and institutionalized older adult. AB - The older adult population is one of the fastest growing segments of the United States population. The number of older adults requiring services in nontraditional settings is expanding rapidly. This paper explores the background, realities, and methods of delivery of optometric services in two nontraditional settings: the home and the long-term care nursing facility. PMID- 2195420 TI - Imaging of the pelvis and hip. AB - Imaging is basic in the orthopedic evaluation of hip disorders. For optimal evaluation of these images, the orthopedic surgeon must not only correlate normal anatomy and pathology with radiographic findings, but must also be familiar with the newer modalities of CT, magnetic resonance imaging and ultrasound and the role and place of these studies in the evaluation of musculoskeletal disorders. This article correlates normal anatomy of the hip with these modalities and discusses the details of these techniques, particularly CT and MRI, that are pertinent to the orthopedic surgeon. PMID- 2195419 TI - Geriatric educational programs. AB - Information on the geriatric patient is needed in the curricula of all health professional programs. During the 1988 Academy Meeting a Symposium on the Graying of America: Optometric Considerations, was held. The following paper will: (1) summarize a recent survey of geriatric education in the United States schools and colleges of optometry, (2) describe two continuing education projects on gerontology conducted for practicing optometrists, and (3) discuss two recently completed projects involving the training of optometric faculty. PMID- 2195421 TI - Fractures of the pelvis. AB - Imaging plays an important role in the evaluation of pelvic fractures. The indications, use, advantages, and limitations of conventional radiography, computed tomography, three-dimensional computed tomography, and radionuclide scanning of pelvic fractures are presented. The mechanisms of injury and radiographic features of the various types of pelvic fractures are discussed. PMID- 2195422 TI - [Surgical treatment of congenital clubfoot in children]. AB - The paper is based on the author's personal experience in the surgical treatment of 438 patients with congenital club foot aged from 9 months to 9 years. Peritalar ligamentocapsulotomy according to the author's method gave good long term results in 82.64% of the children, satisfactory results in 12.83% and not satisfactory results in 4.53% of the patients. The results were studied within 2 to 20 years after the operation and evaluated according to the clinicoroentgenologic findings. Distinguished among the causes of the recurrences have been violations of the orthopaedic regime, reduction in the function of the extensor muscles and pronators and disturbances in the development of the bones of the medial part of the foot. Dissection of the plantar aponeurosis was not performed in any patient. Dislocation of the tendon attachment area on the foot may be advised for the children threatened by a recurrence of club foot of the anterior part of the foot and in passive complete correction of the foot. PMID- 2195424 TI - [A gene inhibiting the development of human retinoblastoma: the prototype of tumor suppressor genes]. AB - One of the most important progress in cancer research of our time is the discovery of protooncogenes, oncogenes and tumor suppressor genes. The authors review the isolation, of the human retinoblastoma (Rb) susceptibility gene, the analysis of Rb protein and their role in the pathogenesis of retinoblastoma and other tumors. PMID- 2195423 TI - [Orthopedic rehabilitation of children after combined treatment of malignant bone tumors]. AB - The report is based on the data concerning 27 children who were given radiotherapy and chemotherapy for osteogenic sarcomas (14), Ewing's sarcomas and reticulosarcoma (10) and malignant giant cell tumours (2). The reconstructive conservative treatment (7 patients) were referred for prevention of contractures and fractures. The orthopaedic surgical correction of the appearing false joints, deformations and defects of the bones (20 patients) was performed 4 to 5 years after the termination of the primary treatment. During the reconstructive period 3 patients with malignant giant cell tumours and osteogenic sarcoma died because of metastases. The authors have made a conclusion about the advantage of extrafocal compression and distraction osteosynthesis over other methods of fixation and correction of deformations in children after the treatment of malignant bone tumours. PMID- 2195425 TI - [Immunomodulator effect of silymarin therapy in chronic alcoholic liver diseases]. AB - The effects of the hepatoprotective, antioxidant drug silymarin (Legalon) on some cellular immune parameters of patients with histologically proven chronic alcoholic liver disease were studied in a six month double blind study. The lectin induced proliferative activity of the lymphocytes got enhanced, the originally low T cell percentage and the originally high CD8+ cell percentage have been normalized, the antibody-dependent and natural cytotoxicity of the lymphocytes decreased during silymarin therapy. All these changes were significant, while in the placebo group no significant changes occurred, except for a moderate elevation of the T cell percentage. Thus, the immunomodulatory activity of silymarin might be involved in the hepatoprotective action of the drug and improves the depressed immunoreactivity of the patients. PMID- 2195426 TI - [Vitamin K 1 concentration and vitamin K-dependent clotting factors in newborn infants after intramuscular and oral administration of vitamin K 1]. AB - Serum concentration of vitamin K1 and activity of vitamin-K-dependent factors II, VII, IX and X were determined before and after vitamin K1 administration in infants. The babies received vitamin K1 intramuscularly or orally. 12 hours after vitamin K1 treatment the mean concentration was increased in the groups receiving vitamin K1 intramusculary or orally, respectively. Serum level of vitamin K1 fell exponentially, the mean half life was about 30 hours in both groups. Activity of vitamin K-dependent clotting factors did not change significantly after intramuscular or oral vitamin K1 administration during the first four-five days of life. It was no direct correlation between the concentration of vitamin K1 and the activity of vitamin-K-dependent clotting factors. This study suggest that oral administration of vitamin K1 is as effective as the intramuscular route. PMID- 2195428 TI - [The publication Mindenes Gyujtemeny from the medical viewpoint]. PMID- 2195427 TI - [Remembering Emil Grosz]. PMID- 2195429 TI - Combined approach to orbital decompression. AB - Upon occasion, surgical orbital decompression is indicated to treat thyroid ophthalmopathy. Of the various approaches described, we feel a combined ophthalmic-otolaryngologic technique is the safest and most effective means of decompressing the orbit. PMID- 2195430 TI - The treatment of papillary and follicular carcinoma of the thyroid. AB - The treatment of patients with differentiated carcinoma of the thyroid is a controversial subject. This article discusses the authors' approach in the clinical practice. A description of the various types of papillary and follicular carcinoma is presented. Diagnostic tests, biologic behavior, and management are reviewed. PMID- 2195431 TI - Total versus subtotal thyroidectomy. Arguments, approaches, and recommendations. AB - Arguments for routine total thyroidectomy or routine, less than total resection have been espoused for treatment of well-differentiated intrathyroidal carcinoma. Numerous reports in the literature support either approach. No prospective randomized studies have been performed, partly because of the indolent nature of the disease. Many reports are also complicated by the failure of the authors to divide patients into high-risk and low-risk groups and to categorize and evaluate fully the histologic types of the resected tumors. Good evidence exists to show that in the majority of cases of intrathyroidal, well-differentiated lesions, bilateral subtotal resection yields results that compare favorably with total thyroidectomy. Logically, at least, a total thyroidectomy would seem to be preferable, because subtotal resection can be imprecise. Therefore, subtotal thyroidectomy can be recommended over total thyroidectomy, if only on the basis of comparison of complications. The type and rate of complications vary among surgeons. Each thyroid surgeon, therefore, must establish an individual complication rate. Total thyroidectomy in inexperienced hands is not recommended. We recommend, therefore, that total thyroidectomy be used selectively by surgeons who have the skill and experience necessary to make the decision intraoperatively. If, for example, during resection of the lobe that contains the primary tumor, the laryngeal nerves and parathyroid glands can be clearly identified and if there is minimal bleeding and trauma, the surgeon may proceed to side two to perform a total thyroidectomy. If the lesion is large, however, with distortion of anatomy, dissection may be difficult even for an experienced surgeon. Intracapsular parathyroids or undiscovered parathyroids on the side of initial resection should prompt the surgeon to perform a subtotal resection on side two. Under these circumstances, the surgeon should not feel that a total thyroidectomy justifies the increased risk. A unilateral resection, such as lobectomy plus isthmusectomy, can be performed with satisfactory long-term results in low-risk patients, that is, in those with small (less than 1.5 cm) unilateral intrathyroidal exposure and in those with no evidence of metastatic disease. Alternately, the AGES criteria of Hay et al can be used to identify patients in low- or high-risk groups. If the decision to perform a bilateral resection is based on the previous criteria, we recommend that a total thyroidectomy be performed only by an experienced surgeon. During surgery, if there is any suggestion that the laryngeal nerves or parathyroid glands would be at increased risk if a total resection were performed, it may be necessary to revert to a subtotal procedure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2195432 TI - Completion thyroidectomy for initially misdiagnosed thyroid cancer. AB - Intraoperative frozen sections fails to diagnose thyroid carcinoma accurately in 16% of cases. In such instances, we recommend that completion thyroidectomy be performed in the patient who has invasive carcinoma, is less than 70 years old, and has a reasonable life expectancy. The procedure should be carried out immediately if the error in diagnosis is discovered within a week; otherwise the procedure should be delayed until 3 to 4 months later. At that time, the recurrent laryngeal nerves and at least two parathyroid glands should be dissected and preserved. A paratracheal lymph node dissection should also be performed and the lower jugular lymph nodes should be sampled. If these jugular lymph nodes are found to be positive, a modified radical neck dissection should be added. The morbidity associated with the completion thyroidectomy is minimal. Postoperatively, a 131I scan of the neck should be carried out and ablative doses of radioactive iodine can be given if the uptake in the thyroid bed is greater than 1.5%. Subsequently, all patients are given thyroid suppressive therapy and are monitored closely. This approach will reduce the local recurrence rate and improve the long-term survival. PMID- 2195433 TI - Hurthle cell neoplasms of the thyroid. AB - The approach to Hurthle cell neoplasms of the thyroid gland remains controversial because there is no consensus on the criteria used to establish malignancy. Invasion into the thyroid capsule, blood vessels, and contiguous structures in the neck and lymph nodes, or distant metastases establishes malignancy. Benign Hurthle cell lesions should be treated with total lobectomy and isthmusectomy. Total thyroidectomy is the recommended treatment for malignant Hurthle cell lesions. PMID- 2195434 TI - Surgical management of thyroid carcinoma with laryngotracheal invasion. AB - Thyroid carcinoma that invades the airway can, in most cases, be treated by partial laryngectomy or partial tracheal resection. Total laryngectomy or circumferential tracheal reconstruction may be required in patients with extensive disease. Closure of subglottic and tracheal defects can be accomplished with the sternocleidomastoid myoperiosteal flap in a simple, single-staged procedure. Patterns of invasion and appropriate reconstruction are described. PMID- 2195435 TI - Evaluation and treatment of complications of thyroid and parathyroid surgery. AB - The major complications of thyroid and parathyroid surgery include hemorrhage, respiratory obstruction, hyperthyroid storm, hypoparathyroidism, and laryngeal nerve injury. In this article, the incidence, diagnosis, and treatment of various complications are reviewed, with emphasis on hypoparathyroidism and vocal cord paralysis, either bilateral or unilateral. Thyroplastic phonosurgery and carbon dioxide laser arytenoidectomy, two recent surgical additions to the rehabilitation of vocal cord paralysis, are described in depth. PMID- 2195436 TI - Repair of the recurrent laryngeal nerve. AB - Surgical repair and reconstruction of the injured recurrent laryngeal nerve are discussed. Tips to avoid inadvertent nerve injury are noted, as are aspects of non-recurring recurrent laryngeal nerves. The controversy regarding recurrent laryngeal nerve anastomosis is updated, and a protocol for management of the injured recurrent laryngeal nerve is presented. PMID- 2195437 TI - Dissecting Canadian health care. PMID- 2195438 TI - Visceral pain: a review of experimental studies. AB - This paper reviews clinical and basic science research reports and is directed toward an understanding of visceral pain, with emphasis on studies related to spinal processing. Four main types of visceral stimuli have been employed in experimental studies of visceral nociception: (1) electrical, (2) mechanical, (3) ischemic, and (4) chemical. Studies of visceral pain are discussed in relation to the use and 'adequacy' of these stimuli and the responses produced (e.g., behavioral, pseudoaffective, neuronal, etc.). We propose a definition of an adequate noxious visceral stimulus and speculate on spinal mechanisms of visceral pain. PMID- 2195439 TI - [The ability of flea species on the common vole from mountainous Dagestan to transmit and preserve the causative agent of plague]. AB - The infection ability and terms of preservation of plague microbe in fleas of common vole from Dagestan high-mountain plague focus (Frontopsylla causasica, Megabothris turbidus, Ctenophthalmus intermedius and Amphipsylla rossica) was studied experimentally. Block formation and transmission of the infection by F. caucasica and M. turbidus was observed. The transmission of plague microbe by Ct. intermedius fleas was first carried out. These species of fleas preserve the infection for a long time. Experiments with fleas of A. rossica yielded negative results. PMID- 2195440 TI - [The efficiency of Rhadinopsylla rothschildi and R. dahurica fleas as vectors of the causative agent of plague in a Transbaikal natural focus]. AB - Experiments have shown that a block of proventriculus arises in 2.1 to 12.5% of infected fleas of R. rothschildi and in 7.2 to 10.5% of R. dahurica. These fleas transmit the plague agent to different animals (Brandt's vole, narrow-skulled vole, Dahurian suslik). The plague microbe is preserved in the organism of infected insects till the end of the experiment, 74 and 24 days respectively. Therefore, the fleas can play a part in the maintenance of plague epizootics in the Transbaikal natural nidus. PMID- 2195441 TI - [The possibility of using attractants for suppressing populations of pasture ixodid ticks and the trend in searching for them]. AB - Evaluation of all known ticks attractants was made to ascertain their suitability to be combined with pesticide in order to control populations of pasture ticks of the genera Ixodes and Dermacentor. Search for attractants among the pheromones of aggregation (for the genus Ixodes) and among substances determining the host's odour (for both genera) was concluded to be most promising. PMID- 2195442 TI - Complex ankle fracture dislocations with syndesmotic diastasis. AB - Ankle fracture dislocations with fibular "diastasis" require anatomic reduction and usually internal fixation for acceptable clinical results. This review discusses anatomic, radiologic, and clinical aspects in the treatment of these injuries. Clinical examples are given. PMID- 2195443 TI - Acromioclavicular joint injuries. AB - A review is presented of the pathophysiology, diagnosis, and treatment of acromioclavicular joint injuries with a discussion of special cases and complications. The results of nonoperative and operative treatments are examined, with particular emphasis on the Mumford and Weaver-Dunn procedures. Conservative treatment is indicated for most acute cases. Weighted films may not be necessary. PMID- 2195444 TI - Arthroscopy update #7. Alternative arthroscopic techniques for meniscus repair. A review. AB - Several treatment options and surgical techniques have evolved for treating vascular zone tears of the meniscus. The rationale and indications for meniscus repair are discussed, and a review of the various arthroscopic meniscal repair techniques is presented. PMID- 2195445 TI - [In vitro antibacterial activity of RU 51746 (sodium salt of cefpodoxime). Results of a multicenter study]. AB - Cefpodoxime proxetil, a new oral cephalosporin, is the prodrug ester of cefpodoxime. Minimal inhibitory concentrations (MIC) of RU 51746 (sodium salt of cefpodoxime: CPD) were evaluated by agar dilution for 1 696 bacterial strains isolated in 5 hospitals. For Enterobacteriaceae, MIC 50 and 90% were respectively (micrograms/ml): (1) naturally non betalactamase producing species: E. coli, Shigella and Salmonella 0.25-0.5; P. mirabilis 0.06-0.12. (II) chromosomal penicillinase producing species: Klebsiella 0.12-1. (III) chromosomal cephalosporinase producing species: E. cloacae and C. freundii 2-greater than 128; S. marcescens 2-64; indole + Proteus 0.25-64; P. stuartii 0.25-16. Activity of CPD was not modified on plasmid mediated penicillinase producing strains, but CPD was inactive on cephalosporinase hyperproducing strains, and on broad spectrum betalactamases producing strains. CPD was inactive on P. aeruginosa (MIC greater than or equal to 64) and on A. baumannii (16-pi 128). Haemophilus, regardless on betalactamase production status, were very susceptible to CPD (MIC less than or equal to 0.25) and B. catarrhalis was generally inhibited by 0.12 to 1. CPD was poorly active on methicillin susceptible Staphylococci (MIC 50 and 90%: 2-4) and inactive on methicillin resistant strains. Enterococci and Listeria monocytogenes were generally resistant; Streptococci A, B, C, G and Pneumococci were inhibited by low concentration: 0.002 to 0.25 (MIC 50 and 90%: 0.016-0.032) whereas MIC for other Streptococci were 0.004 to 32 (MIC 50 and 90%: 0.25-4). These antibacterial properties placed CPD in excellent position among oral cephalosporins. PMID- 2195446 TI - [Comparative antibacterial activity of ceftibuten (SH 39 720) against 150 K. pneumoniae strains producing different beta-lactamases]. AB - Comparative antibacterial activity of ceftibuten (SH 39 720) on 150 K. pneumoniae strains producing different beta-lactamases. MICs of ceftibuten, cefotaxime + clavulanic acid (10 mg/l), ceftazidime and azthreonam were determined for 150 clinical isolates of K. pneumoniae: 15 "wild" type producing only the SHV-1 type beta-lactamase, 15 TEM-1 and 120 producing new "extended spectrum" beta lactamases (48 CTX-1, 9 SHV-2, 4 SHV-3, 35 SHV-4, 24 SHV-5). Against SHV-1 and TEM-1 strains the bacteriostatic activity of ceftibuten was close to that of the other beta-lactams tested. This activity was preserved against strains producing CTX-1, SHV-2, SHV-3 beta-lactamases and MICs were comparable to those of cefotaxime + clavulanic acid. The MICs of ceftibuten against strains producing SHV-4 and SHV-5 beta-lactamases were higher (1 to 8 mg/l) but this level of antibacterial activity was superior to that of the other beta-lactam antibiotics. The bactericidal activity of ceftibuten was evaluated by kill kinetic studies: this activity was preserved against the CTX-A and SHV-2 strains--with concentrations equal to 2 or 4 x CMI a 4 log10 reduction of the bacterial inoculum was obtained at 24 h. A such reduction was not obtained with cefotaxime. This preserved antibacterial activity of ceftibuten against K. pneumoniae producing some new "extended spectrum" beta-lactamases need further studies to state the structure-activity relation-ships of this antibiotic. PMID- 2195447 TI - [In vitro activity of 4 fluoroquinolones against Klebsiella pneumoniae. Distribution according to phenotype resistance to aminoglycosides or beta lactams]. AB - Minimal inhibitory concentrations (MIC) of pefloxacin (PEF), norfloxacin (NOR), ofloxacin (OFL) and ciprofloxacin (CIP) are evaluated by agar dilution against 100 Klebsiella pneumoniae strains isolated in hospital. MIC 50 and 90%, micrograms/ml, are respectively: CIP (0.25/8), OFL (1/16), NOR (1/32), PEF (2/64). We determined the phenotypes PEF/NOR/OFL/CIP by taking into account the critic concentrations of the French Committee for Antibiogram. The results are: SSSS = 45%, RI/RI/RI/RI = 20%, RI/SSS = 19%, RI/RI/RI/S = 8%, RI/RI/SS = 7%. When a strain is resistant to pefloxacin alone, the MICs of the other fluoroquinolones are higher than those of the sensitive strains. The resistance to fluoroquinolones is most frequent in strains that have acquired resistance to aminoglycosides or betalactams, but exists also in strains that have no acquired resistance to these antibiotics. PMID- 2195448 TI - [In vitro antibacterial activity of lomefloxacin, a new fluoroquinolone, against hospital strains. Results of a multicenter study]. AB - Minimal inhibitory concentrations (MICs) of lomefloxacin (LOM) was determined by agar dilution for 2,819 bacterial strains isolated in 1988 in 9 university hospitals. Activity of LOM against nalidixic acid (NAL) susceptible (S) Enterobacteriaceae was close to that of pefloxacin (PEF) (mode MIC: 0.12-0.25 micrograms/ml); like for PEF, this activity was reduced against NAL resistant (R) Enterobacteriaceae (mode MIC: 4). MICs of LOM against P. aeruginosa were between 0.5 and 16 (mode: 2). LOM had also a good activity against NAL S A. baumannii (mode MIC: 0.5) but this activity is reduced against NAL R Acinetobacter (MICs : 4 to 128). LOM was highly active against Haemophilus (mode MIC: 0.06), Gonococci (mode MIC: 0.008), Meningococci (mode MIC: 0.03), Branhamella (mode MIC: 0.12 0.25). LOM showed activity similar to PEF against methicillin susceptible Staphylococci (mode MIC: 0.5-1); the resistant strains are usually methicillin resistant. Similar to the currently available quinolones, LOM is less effective against L. monocytogenes (mode MIC: 8), Enterococci (mode MIC: 4), Streptococci (mode MIC: 4) and Pneumococci (mode MIC: 8). Finally, for the anaerobic bacteria, LOM is more active against Clostridium perfringens (mode MIC: 1) than against Bacteroides fragilis (mode MIC: 32). PMID- 2195449 TI - [Therapeutic potential of ofloxacin in hospital medicine. A French multicenter study]. AB - Bacteriological studies were carried out on samples taken from 1,824 patients in 12 departments of internal medicine (6 University Hospital Departments and 6 Regional Hospital Departments), over a period of six weeks. Four hundred and twenty-two samples were positive on culture. These included 189 urine samples, 81 samples from the respiratory tract and 71 blood samples for culture. Four hundred and forty-four bacterial strains were isolated (including 290 Gram- organisms, 146 Gram+ organisms, 6 intracellular and 2 anaerobic organisms) 427 of which were tested vis a vis ofloxacin. Seventy-five per cent of identified bacteria were susceptible to ofloxacin including 88% Gram- bacteria, 79% staphylococci and 17.5% streptococci. Bacteria resistant to ofloxacin were responsible for 16 out of 183 of infections originating in the community and 29 out of 116 of infections of nosocomial origin. Enterobacterial strains were tested vis a vis nalidixic acid and staphylococcal strains vis a vis oxacillin: 9 of the 30 strains resistant to nalidixic acid were susceptible to ofloxacin, 4 of the 18 strains resistant to oxacillin were susceptible to ofloxacin. These data confirm the therapeutic potential of ofloxacin in the treatment of common infections encountered in hospital medicine. PMID- 2195450 TI - [In vitro antibacterial activity of rokitamycin, a new macrolide antibiotic. Results of a multicenter study]. AB - Minimal inhibitory concentrations (MIC) of rokitamycin (R) were evaluated by agar dilution for 914 bacterial strain isolated in 4 hospitals and classed as a function of susceptibility and resistance to Macrolides-Lincosamides Streptogramines group (MLS). MICs of R ranged from 0.06 to 1 microgram/ml (mode MIC 0.25-0.5) on Staphylococci susceptible to MLS and on MLSB inducible strains; R was inactive on MLSB constitutive strains. MICs of R ranged from 0.008 to 0.5 microgram/ml (mode MIC 0.06 to 0.25) for Streptococci and Pneumococci susceptible to erythromycin (E) and from 0.06 to greater than 128 for strains resistant to E. Enterococci susceptible to E were inhibited by 0.06 to 0.5 microgram/ml (mode MIC 0.5) and strains resistant to E by 0.25 to greater than 128. Haemophilus were inhibited by 0.5 to 0.65 microgram/ml (mode MICs of R ranged generally from 0.016 to 0.5 microgram/ml (mode MIC 0.12) for C. perfringens and from 0.016 to 1 (mode MIC 0.06) for B. fragilis. Thus, R was shown to be among macrolide antibiotics of resistance strains. Its activity was superior to that of other products of this group spiramycin, josamycin, miokamycin, particularly on Gram positive cocci. R had a good activity on Neisseria, Branhamella, anaerobes and, as others macrolides, was poorly active on Haemophilus. PMID- 2195451 TI - [In vitro sensitivity of Chlamydiae to antibiotics]. AB - The in vitro activity of 11 antibiotics against 16 Chlamydia trachomatis strains isolated from genital tract and 2 Chlamydia psittaci strains isolated from pulmonary tract. The CMI determination (the lowest dilution of the drug which inhibited the inclusion development when untreated control give 10(3) IFC) was assessed by growth in cycloheximide treated McCoy cells-antibiotics were added after incubation for 2 hours at 37 degrees C. The CMI values for Chlamydia trachomatis and Chlamydia psittaci are similar. The activity of antibiotics by comparison between CMI90 and serial levels. The CMI90 (mg/l) were: doxycycline = 0.2, minocycline = 0.2, roxythromycine = 0.12, erythromycine = 0.5, spiramycine = 4, rifampicine = 0.016, ofloxacine = 4, ciprofloxacine = 4, pefloxacine = 8, lomefloxacine = 8, fleroxacine = 8. For Chlamydia trachomatis species all the strains have the same sensibility, no resistance was detected. PMID- 2195453 TI - [Interaction of bactericidal serum effect and antibiotics in subminimal inhibitory concentrations on E. coli strains]. AB - Imipenem (IMI) forming round cells in Gram negative rods reduces in subinhibitory concentrations (subMIC) the seroresistance of E. coli. This effect is distinctly more pronounced in a moderately seroresistant strain of E. coli than in a high seroresistant one. Conversely, human serum (HS) increases the sensitivity of E. coli strains to IMI dependent on their original seroresistance. In contrast, ampicillin (AMP), a filament inducer in E. coli, reduces equally seroresistance but only to a minimal degree and that only in a moderately seroresistant strain; the high seroresistant strain was nonreactive in this respect. It was concluded, that a synergism of antibiotics and bactericidal serum effect is predominantly produced with round cell forming antibiotics, whereas filament forming ones show only minimal effects. Moreover, the original seroresistance of strains in apparently important for the degree tho which these phenomena are expressed. PMID- 2195452 TI - [Evaluation of the Mycoplasma Plus and the SIR Mycoplasma kits for quantitative detection and antibiotic susceptibility testing of genital mycoplasma]. AB - We compared the results obtained with two commercially available systems (Diagnostics Pasteur) for the quantitative identification and the antibiotic susceptibility testing of the genital mycoplasmas. Ureaplasma urealyticum and Mycoplasma hominis with established methodologies, i.e. isolation on agar with enumeration by dilutions in broth medium and MIC determinations. The Mycoplasma Plus system, consisting of six cups, was designed for the identification and quantitation of genital mycoplasmas and the detection of yeasts. Used in parallel in 150 clinical specimens, it detected U. urealyticum in 42 out of 43 and M. hominis in 10 out of 11 specimens positive by the established methodology. The SIR Mycoplasma antibiogram, consisting of 16 cups, provided for the testing of 1 or 2 concentrations (micrograms/ml) of each of 8 antibiotics: doxycycline, minocycline and lymecycline (4-8); erythromycin (1-4); josamycin (2-8); clindamycin (2); pristinamycin (2); and ofloxacin (1-4). Using an inoculum of about 10(4)-10(5) organisms/ml, we found that major part of the results was in accord with those obtained with the MIC determined in broth for U. urealyticum and on agar for M. hominis. Strains intermediate or resistant to the tetracyclines were identified. Both systems seemed suitable for clinical laboratory use. PMID- 2195454 TI - [Post-antibiotic effect of imipenem, amikacin and ciprofloxacin against various strains of Serratia marcescens]. AB - The authors compared the post-antibiotic effect (PAE) of imipenem, amikacin, ciprofloxacin, and latamoxef against Serratia marcescens ATCC 13880 (type strain) and against 12 clinical strains belonging to Grimont's most frequent biotypes: A2a, A3a, A3b, A4a, A4b, A5, A6a, A8a, A8b, A8c, TT, TCT. PAE was determined by measuring bacterial growth kinetics after one hour exposure to concentration of 2 x MIC of 10(6) CFUs in Mueller-Hinton broth. Drug removal was by 10-3 dilution of the exposed culture. A PAE was consistently present with imipenem (range 0.8-2.9 hrs), amikacin (range 1.0-4.9 hrs), ciprofloxacin (range 1.4-2.8 hrs). The duration of PAE did not correlate with MIC or Grimont's biotypes. PMID- 2195455 TI - [Direct effect of nitroxoline in the inhibition of bacterial adherence to urinary catheters]. AB - Nitroxolin or 5-nitro-8-hydroxyquinoline, used in the treatment of acute or recurrent uncomplicated urinary tract infection, has been investigated to demonstrate direct inhibitory effect on Escherichia coli adherence to solid surfaces. First of all, influence of growth medium on bacterial adherence was studied. No relation occurs between growth media enhancing production of adhesins and the ability to adhere to solid surfaces. While bacteria are grown on minimal medium, nitroxolin (MIC/16 to MIC/4) can significantly reduce bacterial adherence to urinary catheter of uropathogenic strains of Escherichia coli AL52 and 382. Increasing the concentration of nitroxolin does not proportionally modify this decrease. When growth is realised on LB broth or agar, nitroxolin does not affect bacterial adherence of strain AL52 and higher doses (8 to 32 mg.l-1) are necessary to obtain the same inhibition of adherence of strain 382. Nitroxolin, in certain conditions, can, directly and rapidly, reduce bacterial adherence to solid surfaces. PMID- 2195456 TI - [Frequency and distribution of beta-lactamases in 1792 strains of Klebsiella pneumoniae in France between 1985 and 1988]. AB - In october 1985, 1987 and 1988, all the clinical isolates of K. pneumoniae (respectively 530, 654, 590 strains) were collected in 20 hospitals. The beta lactamases were identified by analytical isoelectrofocusing and by substrate and inhibition profiles. 76 to 81% of the strains produced only one beta-lactamase: SHV-1 type, pI 7.7 (61 to 65%) or PI 7.1 (14%). The TEM-1 betalactamase (pI 5.4) was produced in 1985 by 21% of the strains, 9% in 1987, and 11% in 1988: TEM-2, pI 5.6 by 2% in 1985-87-88. The extended broad spectrum beta-lactamases, able to hydrolyse amino-thiazol-oximino-beta-lactam antibiotics, TEM or SHV type enzymes (SHV-2, pI 7.7, SHV-3, pI 7.1; SHV-4/CAZ-5, pI 7.8; SHV-5/CAZ-4 pI 8.2; CTX-1/TEM 3, pI 6.3) were also detected: 0.75% of the strain (3 strains) in 1985, 8.4% (55 strains) in 1987, 11% (65 strains) in 1988. These extended broad spectrum beta lactamases were found in 2 hospitals in 1985, 10 in 1987 and 9 in 1988. PMID- 2195458 TI - Infectious complications in children with HIV infection. PMID- 2195457 TI - [Enzymatic resistance to cefotaxime in 56 strains of Klebsiella spp., Escherichia coli and Salmonella spp. at a Tunisian hospital (1984-1988)]. AB - The enzymatic and plasmid-encoded resistance towards oxyimino-beta-lactams has been recently reported as related to the production of an extended-spectrum beta lactamase (e.g. SHV-2, CTX-1 or TEM-3), in particular in our hospital since 1984. The prevalence of that resistance has been examined from January 1984 to December 1988 in function of specimen, unit and type of enzyme among 8,421 isolates of Klebsiella spp., E. coli, Salmonella spp. Each isolate showing a diameter of inhibition zone size inferior or equal to 25 mm for cefotaxime, the double disk synergy test was performed between a disk of amoxicillin and a clavulanic acid disk of cefotaxime, ceftriaxone, ceftazidime and aztreonam. In case of synergy, sonicated extracts have been prepared and examined by isoelectrofocusing with the detection of beta-lactamase activity by ceftriaxone and nitrocefin. 56 isolates (K. pneumoniae, K. oxytoca, E. coli, S. wien, S. typhimurium scored positive including 27 in pediatrics, 18 in surgery, and 8 in medicine. 41% of isolates have been obtained from blood cultures and 26.8% from urines. A majority of isolates (49/56) produced the SHV-2 type, but other types mediating the resistance phenotype CTX have been individualized initially by their isoelectric points e.g. 5.4 (TEM-20 in K. pneumoniae in July 1986), 6.4 (TEM-21 in E. coli, 1 K. pneumoniae in July 1988). The prevalence of resistance to cefotaxime from 1984 to 1988 has increased (from 0.3 to 1.4%), the highest rate being observed in pediatrics (5.6% in 1984 and 22.1% in 1988). PMID- 2195459 TI - Gallbladder sludge and antibiotics. PMID- 2195460 TI - Gas gangrene and congenital agranulocytosis. PMID- 2195462 TI - Bacterial tracheitis caused by Streptococcus agalactiae. PMID- 2195461 TI - Diagnosis and management of septic thrombosis of the inferior vena cava caused by Candida tropicalis. PMID- 2195463 TI - Cerebral calcifications in a neonate with candidiasis. PMID- 2195464 TI - [Appendicitis in pregnancy]. AB - The incidence, symptoms, clinical and paraclinical findings, and complications of appendicitis during pregnancy is reviewed. The symptoms and signs do not differ from those in non-pregnant women with the disease. Uterine contractions may occur. The pregnancy ought not to divert the clinicians attention from the disease which is complicated by a considerable foetal mortality, premature labour and abortion. These complications are especially connected with perforated appendicitis. The perforation frequency is related to the delay prior to operation. Immediate appendectomy is recommended as soon as the disease is suspected, making use of prophylactic tocolytic therapy. Antibiotics should be administered according to the usual recommendations. Abdominal delivery should be reserved for obstetric indications only. PMID- 2195466 TI - [Stereologic methods in pathology]. PMID- 2195465 TI - [Good must drive out evil. On cosmetic treatment agents and earlier times' viewpoint on skin diseases]. AB - The interest in skin preparation and "cosmetics" has increased in recent years. This development, which seeks to satisfy the patients' wishes and requirements for a kind but at the same time effective treatment is of historical significance. The treatment of skin diseases was in earlier times pervaded by another attitude, to the effect that evil should drive out evil, e.g. syphilis, scabies and psoriasis. The physician prescribes but it is the patient who executes the treatment, a point more often borne in mind with regard to the diseases of today. PMID- 2195467 TI - Moments in nursing history. 1970. Four hundred postcards. PMID- 2195468 TI - Salt enhances the mutagenicity of nitrosated black beans. PMID- 2195469 TI - Hypotheses for the etiology of colorectal cancer--an overview. AB - Colorectal cancer is the second most common cancer in the United States. Various dietary, colonic, and fecal components have been implicated as causative factors. Although numerous studies have been conducted to test them, so far no one factor has stood out as the most likely cause of colorectal cancer. This review presents the evidence for and against the major factors and concludes that bile acids are the most strongly implicated factors in the etiology of colorectal cancer. PMID- 2195470 TI - Attic treasures: a look at nursing history. AB - Nursing history can provide not only a window on the past but also a clearer sense of the present. Reflections on a description of the "ideal" nurse of nearly fifty years ago reveals both change and continuity. In the change, professional growth in manifested; in the continuity, the perdurable essence of nursing. PMID- 2195471 TI - A sojourn with two nurses of the Virgin Islands. AB - The experiences shared by Ms. Mitchell and Ms. Milligan represent a combined total of more than 80 years of work in nursing. As an introduction to nursing history in a small but vital part of the world, their observations suggest exciting ideas for further research. Such research might include an in-depth exploration of the history of the islands' system of nursing education, a study of the influence of the various island cultures on nursing education and practice, or a comparison between nursing practice in the islands and the mainland. It is hoped that this article might encourage others to explore further the rich history of nursing in the U.S. Virgin Islands. PMID- 2195472 TI - The escalating health care cost of AIDS: who will pay? AB - AIDS is a crisis that has been imposed on an imperfect healthcare system. The flaws are easy to recognize but difficult to treat. Difficult choices about who pays for the medical care for AIDS patients will be made by upper-class and upper middle-class policymakers who are influenced by their own sense of vulnerability and by an aroused public. Social prejudice and moral judgment must be set aside. While the public ethic speaks the language of social justice, public activity often speaks the language of market justice. Beauchamp (1984) cites the philosophy of Anthony Downs when he states that solving social problems "requires painful losses, the restructuring of society and the acceptance of new burdens by the most powerful and the most numerous on behalf of the least powerful or the least numerous" (p. 306). It is characteristic of the public to attend to social problems until "it becomes clear that solving these problems requires painful costs that the dominant interests in society are unwilling to pay" (p. 306). The problem of AIDS care will require painful costs; but unlike many social problems, it will refuse to be hidden, refuse to be contained, refuse to be silenced, and refuse to be equitable in the marketplace and in the social system. PMID- 2195473 TI - Effects of heterogeneous layers of composite and time on composite repair of porcelain. AB - Bond strengths of porcelain/composite resin repair samples, some homogeneous of conventional, hybrid, and microfill materials, some heterogeneous, made by incremental build-up of two of these composites, were evaluated. Samples were allowed to set without disturbance. After storage in 37 degrees C water for intervals of one day, seven days, and 28 days, the test samples were subjected to tensile force until fracture. There were significant differences in bond strengths of homogenous and heterogeneous samples after different storage periods. All mean repair bond strengths were significantly less at seven days than at one or 28 days. Heterogeneous repairs with larger-particle-size composite at the porcelain interface and overlayed with smaller-particle-size composites resulted in higher bond strengths than the homogeneous small-sized composite repairs. Failures of the repairs occurred at the porcelain/composite interface in a statistically significant number, implying that technique exactness at the interface plays an important role in the success of the technique. PMID- 2195474 TI - The use of magnetic resonance imaging in the diagnosis of rotator cuff tears. AB - One hundred consecutive patients with symptoms of chronic subacromial impingement syndrome were evaluated by both arthrography and magnetic resonance imaging (MRI) techniques. By comparing intermediate and T2 weighted images, the ability to identify the normal and abnormal anatomy of the rotator cuff with the MRI was excellent. All 51 patients with arthrogram-proven rotator cuff tears had abnormal MRI scans (100% sensitivity). However, six of the 49 patients with normal arthrograms had abnormal MRI scans (88% specificity). At arthroscopy, four of these patients were found to have moderate to severe partial thickness rotator cuff tears. These findings indicate that in patients with longstanding subacromial impingement syndrome the MRI has an exceptionally high sensitivity for damage to the rotator cuff. PMID- 2195475 TI - Pyloric stenosis: diagnosis and management. PMID- 2195476 TI - Cures in childhood cancer. PMID- 2195477 TI - Interstitial cystitis. An overlooked cause of pelvic pain. AB - Interstitial cystitis is a disease primarily of young and middle-aged women that is characterized by pelvic pain, urinary frequency, and dyspareunia. Its cause is unknown, but defects in the protective glycosaminoglycan layer of the bladder mucosa may be responsible. The diagnosis is mainly one of exclusion. Cystoscopy reveals characteristic glomerulations in the bladder mucosa. Of the available treatments, the most common are intermittent hydrodilation of the bladder and intermittent intravesical instillation of dimethyl sulfoxide. Other methods and medications are currently under investigation. Although interstitial cystitis is uncommon, its potentially devastating effects may be modified or even averted if primary care physicians are familiar with its presentation and maintain a high index of suspicion. PMID- 2195478 TI - Crack abuse. Do you known enough about it? AB - Crack use has increased dramatically because the drug is cheap, highly addictive, and easy to use. As a result, an increased frequency of cocaine-related medical problems has been noted. The effects of crack abuse on fetal outcome and neurobehavioral development are becoming more apparent. In addition, the role of crack use in furthering transmission of sexually transmitted diseases has been documented, and the implications for AIDS transmission have been speculated on. Crack use enhances social disorganization, particularly in poor urban areas, where increased child abuse, neglect, and prostitution are common. Ever present are the financial incentives to increase the number of crack users. Cocaine was once considered a drug for the elite, rich, and famous. Crack clearly has changed that notion. PMID- 2195479 TI - Amphotericin B. Still the 'gold standard' for antifungal therapy. AB - Amphotericin B (Fungizone) remains the cornerstone of antifungal therapy because of its broad-spectrum fungicidal activity and rapid onset of action. Ketoconazole (Nizoral) and the new triazoles are welcome additions to the therapeutic armamentarium but do not replace amphotericin B. Adverse side effects of amphotericin B treatment are usually manageable and often preventable. Careful attention to detail reduces immediate toxicity and allows completion of the desired therapeutic course without an undue risk of permanent nephrotoxicity. PMID- 2195480 TI - When to worry about hypoglycemia. AB - The important causes of hypoglycemia unrelated to known diabetes are relatively few. Postprandial hypoglycemia is a relatively benign disorder. Fasting hypoglycemia is more serious and may be caused by metabolic disturbances or tumors. Several hereditary disorders cause hypoglycemia in infants and must be diagnosed and treated before serious damage occurs. A systematic clinical approach increases the likelihood of making the correct diagnosis in a timely fashion. PMID- 2195481 TI - Facial wrinkles. Prevention and nonsurgical correction. AB - There is no way to age without getting wrinkles. However, patients can be taught how to retard the onset of wrinkles by avoiding unprotected sun exposure, unnecessary facial movements, and certain sleeping positions. Relatively simple non-surgical techniques are available for correction of wrinkles. Small wrinkles can be treated with exfoliation, topical tretinoin (Retin-A), or topical alpha hydroxy acids. Large wrinkles can be improved with implantation of bovine collagen, silicone, or fat extracted from the abdomen or thigh of the patient. Each method is effective when used for the correct indications. PMID- 2195482 TI - Vacation diarrhea. How should it be managed? AB - Traveler's diarrhea in North America is most often a self-limited disease that requires little medical intervention unless the course is prolonged or especially severe. Diagnosis is almost always made by a stool examination or culture. The most common causative organisms are Campylobacter jejuni and Giardia lamblia. Enterotoxigenic Escherichia coli is a less frequent cause. Patients should be advised regarding the need for fluid replacement. Antibiotic therapy should be considered only in rare circumstances. PMID- 2195483 TI - The isolation of salmonellae from poultry environmental samples by several enrichment procedures using plating media with and without novobiocin. AB - A two-part study was conducted to examine the efficacy of several enrichment broth techniques and of plating media for detecting salmonellae from poultry environmental samples. The data are reported on pooled samples collected from five poultry houses. The samples were cultured for salmonellae, using up to four different enrichment procedures and employing plating media with and without novobiocin. The primary enrichment-broth procedures were: 1) buffered peptone water preenrichment to Hajna's tetrathionate (TT) broth; and 2) direct inoculation in TT broth. The delayed secondary-enrichment procedure involved prolonged incubation at room temperature and transfer of the primary broths. The plating media consisted of: 1) xylose lysine desoxycholate agar (XLD); 2) xylose lysine desoxycholate agar containing 15 or 20 micrograms per mL of novobiocin (XLDN); 3) brilliant green sulfapyridine agar (BGSP); and 4) brillant green agar containing 20 micrograms per mL of novobiocin (BGN). Of the 94 Salmonella positive recoveries from the enrichment broths in which complete comparisons could be made, an average of 75% were recovered from the primary enrichment broths and an average of 86% were recovered from the delayed secondary-enrichment broths. Of the 254 Salmonella-positive isolations in which complete comparisons could be made, an average of 65% were isolated on the plating media without novobiocin and an average of 97% were isolated on the plating media containing novobiocin. Overall, the delayed secondary enrichment and enteric plates supplemented with novobiocin significantly improved Salmonella detection from the farm environmental samples. PMID- 2195484 TI - Secretory pattern of growth hormone, insulin, and related metabolites in growing male turkeys: effects of overnight fasting and refeeding. AB - The effect of an overnight fast on the secretory profile of growth hormone (GH), insulin, and related metabolites [glucose, nonesterified fatty acids (NEFA) and triglycerides (TG)] was determined in two separate experiments with 8- and 9-wk old male turkeys. Toms were provided feed ad libitum or were fasted 20 h prior to sampling. Blood samples (.6 to .7 mL) were collected every 10 min for 8 h from the toms showing a positive weight gain between cannulation and the initiation of the experiment. Overall and baseline, GH levels were higher for the fasted birds versus the fed birds. The GH peaks for the fasted birds were of shorter duration than those for the fed birds, but were more frequent. The plasma NEFA levels of the fasted birds were higher than those of the fed birds. Plasma TG was lower for the fasted than the fed group. Insulin, which was secreted in a pulsatile fashion, was lower for the fasted versus the fed birds. Fasting produced no change in plasma glucose. A separate group of fasted males was refed after 4 h of sampling; the plasma levels of GH, insulin, and metabolites returned to those observed in birds given feed ad libitum within 30 min of refeeding. There appeared to be no relation between the pulsatile release of GH and the circulating levels of NEFA. PMID- 2195485 TI - The use of carcass halves for reducing the variability in salmonellae numbers with broiler-processing trials. AB - Two similar trials were conducted in order to compare the variability in the number of salmonellae between the right and left sides of individual broiler carcasses with the variability among carcasses. In both trials, the variation between carcass sides was equal and was significantly less than the variation among carcasses. For trials involving bactericidal treatment, the authors would suggest that the utilization of carcass halves (one side for control, the other for treatment) would allow for a more-sensitive evaluation of treatment effects. PMID- 2195486 TI - Clinical pharmacology of splanchnic circulation in cirrhosis. PMID- 2195487 TI - Evaluation of drug safety by toxicological test procedures as provided by regulatory laws: an overview. PMID- 2195488 TI - Nonreimbursed home health care: beyond the bills. AB - The unprecedented growth in the home care industry over the past decade has produced a highly competitive environment for care delivery. To survive, most agencies are implementing strategies to maximize reimbursable care. This focus, while likely to improve an agency's financial situation, is fraught with potential problems. Reimbursed care represents only a small portion of the care that is required and delivered. Still, aside from anecdotes, little reporting has been done to document such additional service, much less to consider the consequences of reducing or deleting it. We selected a sample of 350 public health home care episodes throughout Virginia, and reviewed billing records to determine the number of billed home visits attached to them. We then reviewed home health records for the matching episodes and recorded all visits and other care-related activities (e.g., telephone calls, conferences, laboratory trips). Total home visits increased, with an average of 1.5 unbilled home visits per episode. In addition, 10 additional care-related activities take place per patient, none of which is billed. These findings represent one of the first attempts to quantify the amounts and types of nonbilled care delivered by nurses. This care consumes significant nursing resources and, as a result, may be destined to be reduced or totally eliminated. PMID- 2195489 TI - Information needs in home care: a review and analysis. AB - Before prospective payment can be implemented in home care, providers and administrators in home care agencies require information in a variety of areas. This article reviews the literature on several factors likely to influence the market for home care services, including hospital use trends, the response to diagnosis-related groups by home care agencies, proposed reimbursement patterns, patient disease and demographic profiles, and patient needs. Research must be conducted in several areas before prospective payment can be implemented in home care. PMID- 2195490 TI - Psychosocial aspects of genital herpes: a review of the literature. AB - Understanding the psychosocial aspects of genital herpes will enable community health nurses to be aware of the range of responses by young adults to the disease and of interventions suggested by research. Reviewed are the epidemiology of genital herpes infection; the knowledge, attitudes, and behavior related to it; the psychosocial consequences of and techniques for coping and adaptation to living with the disease; responses to treatment; and implications for community health nursing. PMID- 2195491 TI - Oily fish and heart disease. PMID- 2195493 TI - High-performance liquid chromatographic (HPLC) and HPLC-mass spectrometric (MS) analysis of the degradation of the luteinizing hormone-releasing hormone (LH-RH) antagonist RS-26306 in aqueous solution. AB - The kinetics of the degradation of an LH-RH antagonist, RS-26306,1, in aqueous solution from pH 1 to pH 11 were studied by reverse-phase HPLC. The pH-rate profiles at 50, 60, and 80 degrees C were U-shaped with the rate law of kobs = kHaH + kw + kOHaOH. The predicted 25 degrees C shelf life at the pH of maximum stability, pH approximately 5, is greater than 10 years. The products from the degradation were analyzed by HPLC-MS using thermospray ionization. Below pH 3, the primary product, 2, forms from the acid-catalyzed deamidation of the C terminal amide. Above pH 7, epimerization of the individual amino acids is the principal reaction. Between pH 4 and pH 6, intramolecular serine-catalyzed peptide hydrolysis becomes important, yielding a tripeptide, 3, and a heptapeptide, 4. At the pH of maximum stability all three pathways for degradation are observed. PMID- 2195494 TI - Testing of insulin hexamer-stabilizing ligands using theoretical binding, microcalorimetry, and nuclear magnetic resonance (NMR) line broadening techniques. AB - In a study aimed at the development of a long-acting insulin preparation, Manallack and co-workers (5) reported on the design of small organic molecules which have the potential to bind to insulin and stabilize its hexameric aggregate. Two of the molecules that were designed with their computer graphics program were thought to be particularly promising as ligands: benzene-p disulfonate and benzene-p-diphosphonate. In the present work, the insulin binding abilities of these molecules have been thoroughly tested. A theoretical binding program, GRID, was used to calculate the binding energetics of the molecules and to predict the most probable site of their binding. Microcalorimetry and NMR line broadening techniques were used to measure the actual binding reactions of the ligands. For both compounds, no evidence of binding to insulin was ever observed in either the microcalorimetry or the NMR studies. In contrast, a series of phenolic ligands commonly used as preservatives for insulin showed evidence of substantial binding using either method. An explanation has been proposed for this apparent discrepancy between computer predictions and actual experimental data: The theoretical programs do not take solvation effects of the aqueous medium into account. Solvation effects would tend to inhibit binding of the ionized ligand molecules due to charge delocalization and steric crowding. PMID- 2195495 TI - The use of microcalorimetry to measure thermodynamic parameters of the binding of ligands to insulin. AB - Flow microcalorimetry was used to measure the free energies, enthalpies, and entropies of interactions between the hormone insulin and small ligand molecules or ions. Measurable amounts of heat were obtained for binding of four phenolic preservative molecules--phenol, meta-cresol, resorcinol, and methylparaben--to both two-zinc and zinc-free insulin and for binding of zinc ions to zinc-free insulin. All of the reactions were spontaneous, but the phenolic binding was driven by enthalpy, while that of zinc was entropy-driven. A combination of van der Waals interactions, hydrophobic effects, and protein conformational changes appeared to be involved in binding of the phenolic ligands. Zinc ions displayed two types of binding to insulin, both involving ion-dipole interactions. PMID- 2195492 TI - The use of cultured epithelial and endothelial cells for drug transport and metabolism studies. AB - In an effort to develop novel strategies for delivery of drug candidates arising from rational drug design and recombinant DNA technology, pharmaceutical scientists have begun to employ the techniques of cell culture to study drug transport and metabolism at specific biological barriers. This review describes some of the general factors that should be considered in developing a cell culture model for transport studies and metabolism studies. In addition, we review in detail the recent progress that has been made in establishing, validating, and using cell cultures of epithelial barriers (e.g., cells that constitute the intestinal, rectal, buccal, sublingual, nasal, and ophthalmic mucosa as well as the epidermis of the skin) and the endothelial barriers (e.g., brain microvessel endothelial cells). PMID- 2195496 TI - Characterization of epidermal growth factor receptors on plasma membranes isolated from rat gastric mucosa. AB - The binding of human epidermal growth factor (hEGF), beta-urogastrone, to plasma membranes isolated from rat gastric mucosa was studied to characterize gastric EGF receptors. The binding of [125I]hEGF was temperature dependent, reversible, and saturable. A single class of binding sites for EGF with a dissociation constant of 0.42 nM and maximal binding capacity of 42 fmol/mg protein was suggested. There was little change in the binding of [125I]hEGF upon addition of peptide hormones (secretin, insulin), antiulcer drugs (cimetidine), or an ulcer inducing reagent (aspirin). Cross-linking of [125I]hEGF to gastric plasma membranes with the use of disuccinimidyl suberate resulted in the labeling of a protein of 150 kDa. These results indicate the presence of EGF receptors on plasma membranes of rat gastric mucosa. PMID- 2195497 TI - Applicability of 19-DEJ-1 monoclonal antibody for the prenatal diagnosis or exclusion of junctional epidermolysis bullosa. AB - Recently a monoclonal antibody (19-DEJ-1) was produced with binding specificity for the mid-lamina lucida of the skin dermo-epidermal junction, in very close association with overlying hemidesmosomes. Since skin cleavage occurs within the lamina lucida in the inherited blistering disorder, junctional epidermolysis bullosa (EB), and is associated with aberrations in the morphology and/or number of hemidesmosomes in such tissue, we have sought to determine whether this monoclonal antibody could be used for prenatal diagnosis. Fetoscopy-directed skin biopsies were obtained from two fetuses at risk for junctional EB and post-mortem samples from two other fetuses with the Herlitz type of junctional EB, the latter after prenatal diagnosis by electron microscopy and termination of each pregnancy. Specimens were examined in part by light and electron microscopy for evidence of skin cleavage or other alterations in morphology, and in part by indirect immunofluorescence for altered basement membrane antigenicity. Three of four fetuses were shown to have intra-lamina lucida blister formation indicative of, and hemidesmosome hypoplasia proving, junctional EB. Each was also shown to lack expression of GB3 and 19-DEJ-1 antigens, consistent with findings noted postnatally in junctional EB; diagnosis was confirmed in each at the time of therapeutic abortion. A fourth fetus had no abnormalities detected; lack of disease involvement was confirmed at the time of delivery, and subsequently over 8 months of careful serial evaluation. We conclude that 19-DEJ-1 monoclonal antibody is an accurate and sensitive immunohistochemical probe for junctional EB, and may be employed in the prenatal diagnostic evaluation of fetuses at risk for this disorder. PMID- 2195498 TI - Prenatal diagnosis of inherited metabolic disorders by quantitation of characteristic metabolites in amniotic fluid: facts and future. AB - An attempt is made to summarize as completely as possible what is known about the prenatal diagnosis of amino- and organic acidurias by direct measurement of characteristic metabolites in amniotic fluid, and to indicate which disorders can potentially be diagnosed prenatally by direct quantitation of metabolites. Furthermore, the disorders are mentioned in which the prenatal diagnosis was proven to be unsuccessful by this approach. The prenatal diagnoses of a case of propionic acidemia and a case of tyrosinemia type I in the 11th and 12th week of gestational age, respectively, are reported and the prospects of performing amniocentesis in the first trimester for prenatal diagnosis are discussed. PMID- 2195499 TI - Umbilical cord pseudocyst in trisomy 18. PMID- 2195500 TI - [Molecular forms of triacylglycerols in edible vegetable oils (review of the literature)]. AB - Data on the composition of major and minor molecular forms of triacylglycerols from edible vegetable oils are reviewed. To estimate the food and biological value of vegetable oils, an attempt was made to classify them according to their triacylglycerol composition. PMID- 2195501 TI - [The composition of amino acid-peptide mixtures obtained during hydrolysis of proteins]. AB - The composition of the amino acid and peptide fraction of the protein hydrolyzate and its dependence upon the spray-drying process at elevated temperatures were investigated by GLC and GLC-MS. Spray-drying leads to decrease in the Glu and Met contents, to transformation of Cys into cystine and to formation of lactames (pyroglutamic acid and pyrrolidone) and diketopiperazines. Some dipeptides, acetylproline, paraffines, fatty acid pyridinecarboxylic and lactic acids, ethylene glycol were identified in the fraction. The incidental occurrence of these compounds should be taken into account when investigating the biological activity of protein hydrolyzates. PMID- 2195502 TI - [The lung in heart diseases]. AB - The effects of "hypocirculation" and "hypercirculation" of the lungs are small. Hypocirculation has an influence of the ventilation/perfusion ratio, and can thus contribute to hypocapnia. In the early stages, hypercirculation--in particular via a left-to-right shung, leads to an increase in diffusion capacity; after a course of many years, a "counter-situation" occurs. Progressive pulmonary hypertension, as is exemplified for mitral stenosis, leads to measurable restrictive and obstructive impairment of function, and possible to unspecific hyper-reaction, as also, over the long-term, to a diminishement in membrane diffusion capacity. Chronic left heart failure is characterised by interstitial oedema at the level of the alveolar and bronchial capillary beds. The results are measurable restrictions in the static volumes, and in particular of the obstruction parameters and the closing volume that involve the small airways. In the individual case, no statement as to the extent of left heart failure is possible. In the passive pulmonary hypertension phase, diffusion capacity increases; in the further course of the disease, with development of interstitial and alveolar oedema, it decreases again. In acute left heart failure, the persistance and/or extent of pulmonary oedema is not determined solely by the magnitude of the pulmonary venous pressure. Permeability oedema--brought about by mediators--would appear to be significant on the basis of animal experiments. Not infrequently, left cardiac failure leads to small pleural effusions which occur in combination with substantial atelectasia, the aetiology of which is unclear. Interpretation difficulties are caused by the clinical findings and function analytical data obtained in patients with a combination of chronic lung disease and reducted volume storage capacity of the pulmonary circulation and of the left heart failure, a common situation in the elderly patient. Diminished pulmonary function parameters that fail to adequate respond to bronchodilators may be an expression of left ventricular failure. PMID- 2195503 TI - [Lung involvement in collagen diseases]. AB - Connective tissue diseases are relatively frequently associated with pulmonary manifestations, and should thus always be included in the pneumological differential diagnostic evaluation. The nature and incidence of the various pulmonary forms of manifestation are discussed. Pulmonary accompanying reactions (clinically and radiologically "silent" alveolitis) which, if granulocytic, have proved to represent a negative prognostic factor, must be distinguished from these manifestations. The diagnosis and treatment of the underlying disorder and the pulmonary manifestations are briefly discussed--with respect to treatment, in particular to immunosuppressive or cytostatic agents. It is shown that, today, the diagnostic evaluation generally presents no problems, while treatment often produces unsatisfactory results. PMID- 2195504 TI - [Disorders of neuromuscular function and respiration]. AB - Neuromuscular disorders of varying aetiology frequently lead to respiratory failure. This situation contrasts with the rare application of suitable tests of pulmonary function in this group of patients. As a result, respiratory complications are not detected until they have progressed to a terminal stage. With the sequential measurement of vital capacity, and a determination of the maximum inspiratory and expiratory pressures (PImax and PEmax), we have reliable and practicable diagnostic measures available that permit the recognition of respiratory failure at an early stage. This fact is of particular importance, since the application of modern ventilation techniques in suitable patients can make a substantial contribution towards both improving the patient's quality of life and prolonging it. PMID- 2195505 TI - [Lung metastases]. AB - Neither functionally not metabolically do pulmonary metastases represent an isolated problem of the respiratory organs. Rather, they are a problem of the organism as a whole, and represent the "home straight" that is common to almost all malignant diseases. This "home straight" has not yet been fully understood from the pathophysiological point of view, is not always readily accessible to diagnostic evaluation, and its response to treatment is disappointing. The key to successful therapy in the future will, presumably, be seen not so much in the eradication of existing metastases, as in the avoidance of their manifestation. Tangible results--that is, clinically useful results--are, as yet, not realiable. PMID- 2195506 TI - [Paraneoplastic syndromes--the endocrine system and the lungs]. AB - By the term "paraneoplastic syndrome" is meant a constellation of symptoms and findings that can be traced back to a tumor, but which are not caused by local or metastatic mechanisms. Such paraneoplastic syndromes can suggest the diagnosis of a tumor, or serve to chart the course of known tumor disease. When the pathophysiology is known, the mediators (hormones) may replace the clinical syndrome as useful parameters. With respect to the pathobiology of tumors, an analysis of paraneoplastic syndromes would seem to be highly promising, and might possibly form the basis for the development of new therapeutic concepts. PMID- 2195507 TI - [Gastroesophageal reflux and lung diseases]. AB - In a number of patients there is evidence of an unfavourable interaction between gastro-oesophageal reflux (GER) and pulmonary disease, that takes the form of a vicious circle: first GER can induce and maintain chronic bronchopulmonary inflammation by recurrent unnoticed aspirations and, secondly chemical irritation of the oesophageal mucosa causes airway obstruction by vagally-mediated reflexes. Obstructive airway disease in turn favours GER via anatomical functional and physiological factors. Thus the prevalence of GER is increased to 30-40% in patients with asthma and chronic bronchitis, as compared with only 5-10% in the general population. A positive history of productive cough, nocturnal respiratory symptoms and recurrent hoarseness may be helpful in detecting an important relationship between GER and chronic airway disease. The modified Bernstein-test, radionuclide studies and detailed sleep studies are suitable methods of establishing the diagnosis. Antireflux diets, H2-antagonists and antacids are accepted treatment in the adult, and may obviate surgical procedures in most patients. In clinical practice the relationship between GER and pulmonary diseases should be considered routinely, in order to initiate early and effective treatment and to end the vicious circle. PMID- 2195508 TI - [Sarcoidosis as a multi-organ disease]. AB - Sarcoidosis meets the criteria for multi-organ disease, which differs from systemic disease in the following points: The preferred primary organ (lungs) is known, immunological processes take place only in the organs involved (T helper lymphocyte accumulation), the clinical picture depends upon the organ involvement, and granulomas are typical of the disorder. The clinical significance of the various organ manifestations covers a broad spectrum, which can also include a threat to life (myocardium), blindness, chronic invalidism (pulmonary fibrosis, hepatopathy, nephropathy), and cosmetic impairment (cutaneous sarcoidosis). Numerous organ manifestations have no clinical significance, and some are both rare and limited (tumorous CNS involvement). So called overlap syndromes have characteristic features common to both multi-organ and systemic diseases. In addition to characteristic sarcoidosis manifestation in an organ, signs of a generalized disorder are also detectable. Examples are primary biliary cirrhosis, Crohn's disease, coeliac disease, Whipple's disease, TASS (Thyrotoxicosis, Addison, Sjogren, Sarcoidosis) as lymphomas and inflammatory diseases (tuberculosis). Outside of the primary organ, these manifestations are often clinically latent. Selective investigations bronchoalveolar lavage), however, can demonstrate the presence of sarcoidosis alveolitis. It is demonstrated that for the clinician, differentiation of multi organ from systemic disease is meaningful in particular with respect to therapeutic consequences. In the individual case, however, possible overlapping must always be borne in mind. PMID- 2195509 TI - [Side-effects of treatment on the structure of the lung]. AB - The morphology of therapy-associated changes in the lungs is determined by largely unspecific findings, since various toxic injuries lead to a formal pathogenetically almost identical reaction pattern. In addition to direct toxic injuries, the morphological investigation also reveals evidence of allergic and individual-specific complex reaction patterns. In an early phase (Phase I), pathological-anatomical degenerative changes affecting the endothelial and epithelial cells, basal membrane, mesenchymal and matrix structures--initially functionally partially reversible, but then extending to complete necroses--can be found. Measurable functional disorders are demonstrated in particular by disturbed permeability of the capillaries, increased interstitial fluid, and functional disorders of the pneumocytes (shortage of surfactant, defective intercellular connections). The cellular exsudative phase (Phase II) is characterised by an accumulation and stimulation of macrophages, a variably pronounced immunological infiltration with and without eosinophilia, and regenerative findings affecting membrane structures, endothelial and epithelial cells. The fibrotic, chronic phase (Phase III) leads to largely irreparable, predominantly interstitial, fibrosis in the region of the non-fibrillar matrix, and to an increased production of collagenous fibres, elastic fibres and muscle fibres by myofibroblasts in an interaction with macrophages. Atypical proliferations of pneumocyts, pronounced eosinophilia, predominantly endangiitic vascular changes, etc. may, to some extent, indicate injuries by certain groups of substances or ionising radiation. Heterogeneous, multi-focal toxic pulmonary changes, that permit only limited interpretation in biopsy material, together with the possibilities of prior lung diseases in the elderly patients require caution on the part of the pathologist when it comes to a causal-pathogenetic interpretation of formal-pathogenetically unequivocally establishable findings. PMID- 2195510 TI - [Unwanted effects of therapeutic drugs on the structure and function of the lung from a clinico-pharmacologic viewpoint]. AB - Undesirable drug effects occur in the lung with about 35 frequently employed drugs and can be life-threatening or life-shortening. As examples, the clinical pattern, course, pathomechanism and therapy are shown for nitrofurantoin, bleomycin, amiodaron, opiates nitrofurantoin, and acetyl salicylic acid. The kinetic aspects of the occurrence and disappearance of the undesirable drug effects are stressed. If the kinetics of amiodaron, for example, are taken into consideration, the occurrence and course of the pulmonary affection can be understood. The use of steroids in case of pulmonary involvement of bleomycin and amiodaron is critically assessed. PMID- 2195512 TI - [Thoracoscopic pericardial fenestration--diagnostic and therapeutic aspects]. AB - This article reports on four tumour patients with extensive, but cytologically innocuous pericardial effusion. In three cases, a tumour-cell-negative pleural effusion, on the left, was also present. Thoracoscopy showed that the pleura were unremarkable, whereupon, with the aid of the biopsy forceps--in one case the Nd:YAG laser--the pericardium was opened. The procedure provided diagnostically high-yielding material; in addition, pericardial tamponade was "permanently" eliminated (period of observation up to 4 years). This shows that, in addition to its diagnostic value, thoracoscopic pericardial fenestration also can be therapeutic. It represents an alternative to the surgical approach. PMID- 2195511 TI - [Clinical and functional disorders in side effects of drugs on the lung]. AB - Although, at 5% of all drug-related adverse reactions in the human organism, drug associated injuries to the lungs are not very common, their consequences can be substantial: the disordering of the organ, often detected late, can lead to irreversible fibrosis. The detection of a drug-induced adverse reaction in the lungs is difficult on account of the usually complex situation presenting: specific pathological signs are lacking, the underlying disease being treated may itself mimic adverse drug reactions, and often several drugs or forms of treatment are being employed simultaneously, so that the causal drug is difficult to identify. In principle, a differentiation must be made between cytotoxic drugs that "follow" a dose-effect curve, and idiosyncratic, sporadic effects, together with dose that involve the lung via drug-induced erythematodes. In contrast, undesired adverse effects manifesting in the airways, pulmonary vessels, pleura or respiratory muscles are usually easier to diagnose and treat. In the daily application of potentially pulmotoxic drugs, the decisive point is monitoring by means of pulmonary function parameters, which may preceded clinical manifestation by weeks. In this manner, irreversible damage can be avoided. PMID- 2195513 TI - [Transitory bacteremia in bronchologic-biopsy procedures]. AB - In 105 patients, the incidence of transitory bacteraemia seen following bronchological-bioptic interventions was investigated. In three patients (2.9%), the identical pathogens were detected both in the bronchial secretion and in venous blood culture following bronchoscopy. PMID- 2195514 TI - [New technics for producing inhalation aerosols--initial experiences and results with the piezoelectric inhalation device]. AB - In the treatment of chronic obstructive airway diseases, the inhalative application of medicaments with a bronchodilatory effect is given preference throughout the world. In addition to inhalation solutions and powder capsules, so called metered-dose aerosols have formed an established part of the treatment plan for approximately 30 years now. With the piezoelectric inhalation device, a fully portable ultrasonic atomiser that is small enough to fit within the pocket, has been developed for the first time. In this device, the piezoelectric effect is utilised to produced, pressure-free, microfine aerosols. Within it, an accurately metered volume containing the therapeutic dose is applied to an atomising element oscillating in the ultrasonic range. The particle spectrum generated with the piezo-system corresponds, in terms of size, to that of metered aerosol devices, and the mean particle diameter is approximately 2.1 microns. The atomisation process takes approximately one second. PMID- 2195515 TI - [Effect of nifedipine alone and in combination with salbutamol on the beat frequency of human nasal cilia]. AB - In 25 patients suffering from chronic obstructive bronchitis, it has been shown that the administration of nifedipine brings about a decrease in the beat rate of nasal cilia which, in the individual case, may be very marked. The addition of salbutamol can more than compensate for this decrease in cilial beat rate. PMID- 2195516 TI - [Serum theophylline concentrations in patients with chronic obstructive lung diseases: a comparison of 2 methods]. AB - A total of 120 samples of serum were obtained from 8 patients with COPD and submitted to a comparative analysis of serum theophylline levels employing the TDX and the EMIT methods of determination. At the same time, two different slow release preparations of theophylline were compared, their kinetics investigated, and their effects tested using body plethysmography. For this open, randomized cross-over preliminary investigation, numerous inclusion and exclusion criteria were applied. PMID- 2195517 TI - [Perioperative preventive use of antibiotics in thoracic surgery--results of a controlled randomized study with optocillin]. AB - There seems to be general agreement that antibiotic prophylaxis should be provided for patients undergoing resections of the lung. In order to obtain further information about the extent of resection beyond which this is necessary, and also to establish the type of prophylaxis that is meaningful over the long term, we carried out a controlled study involving two groups of 100 patients each. In the first group, who received minor resections, ultrashort-term prophylaxis was compared with an 0 group. We were able to show that in high-risk patients with prior pulmonary diseases, prophylaxis is indeed meaningful. In the second group of patients undergoing major resections, antibiotic prophylaxis must be provided; a one-day administration suffices, and long-term administration fails to offer any further advantages. PMID- 2195519 TI - [Comparison of the course of oxygen saturation and transcutaneous oxygen pressure in nonspecific inhalative provocation]. AB - In the case of the unspecific inhalative provocative test, a drop in arterial oxygen pressure often occurs, and can be recorded continuously, with the aid of transcutaneous measurements. In 39 patients, the course of oxygen pressure measured transcutaneously (tcpO2) was compared with the continuous measurement of oxygen saturation (SaO2) employing pulse oximetry. A close correlation was found to exist between maximum tcpO2 and maximum SaO2 decrease. The continuous measurement of oxygen saturation is thus also suitable for the monitoring of the course and for assessing an unspecific inhalative provocation; owing to the course of the oxygen-binding curve, however, the changes are only slight. A positive reaction may be suspected when the oxygen saturation decreases at least 3 per cent. PMID- 2195518 TI - [Effect of nitrogen dioxide on exercise-induced bronchial asthma and the sensitivity of the respiratory tract to methacholine]. AB - In patients with bronchial asthma, airway hyperreactivity may be further increased by exposure to low concentrations of nitrogen dioxide. We studied the effect of inhaled nitrogen dioxide in 11 patients with bronchial asthma who presented with normal lung function values. On two different days, 20 min tidal breathing of either filtered air or 0.25 ppm nitrogen dioxide was followed by bicycle exercise (average minute ventilation 30 l/min). One hour after the end of exercise, we performed a methacholine provocation challenge and determined PC100SRaw. The methacholine provocation challenge was repeated on another day (control day). Mean (SEM) SRaw increased by 79.8 (23.8) % and 82.4 (24.9) % after breathing of filtered air and nitrogen dioxide during exercise, respectively (n.s.). Mean (SEM) PC100SRaw was 0.409 (0.205), 0.407 (0.201) and 0.455 (0.181) mg/ml after breathing of filtered air, nitrogen dioxide and on the control day, respectively (n.s.). We conclude that in mild asthmatics short-term exposure to 0.25 ppm nitrogen dioxide does not enhance airway responsiveness to exercise or methacholine. PMID- 2195520 TI - [Dependence of bronchial hyperreactivity on the initial value of airway resistance]. AB - In 403 patients, the influence of the initial value of the airway resistance on the incidence and extent of a positive reaction after an unspecific inhalative provocation with methacholine was investigated. The higher the original airway resistance was, the greater was the probability of obtaining a positive reaction. At an original resistance of more than 4 cm H2O/l/sec. all patients responded with an increase in airway resistance to more than 6 cm H2O/l/sec. In 91 per cent of these patients, the Rt figure increased more than 100 per cent. The extent of the increase in airway resistance following a positive response was independent of the initial value; the effect of subsequent spasmolysis following a positive test result, showed no dependence on the airway resistance prior to provocation. PMID- 2195521 TI - [General environmental pollutants and passive smoking]. AB - Epidemiological studies-especially data from smog episodes-indicate that antropogenous outdoor air pollution exercises a deleterious effect on health and particularly on the respiratory organs. Controlled exposure test in animals and man confirm this. The main pollutants are SO2, suspended dust particles (dust aerosols or solid atmospheric condensation nuclei) as well as NO2 (NOx) and O3. The adverse influence of quite a number of meteorological factors such as low temperature and inversion cannot be denied. During smog conditions in January 1985 in the Federal Republic of Germany there was a highly significant negative correlation between atmospheric temperature and the rate of exacerbations of bronchitis. Indoor air pollution is gaining in importance. Airtight sealing of buildings associated with reduced indoor ventilation results in novel health upsets ("sick building syndrome"). Interiors are characterised by an accumulation of CO2, CO, NO2, dust aerosols and various organic substances such as benzene, benzypyrene, formaldehyde, nitrosamines etc. Cigarette smoke is a frequent cause of indoor air pollution. The possible unhealthy effects of passive smoking (mainly the inhalation of sidestream smoke) have been frequently studied. Infants of smoking parents are more often affected by respiratory diseases than non exposed children. The same applies to schoolchildren: the incidence of bronchial signs and symptoms increases with increasing smoke consumptions of the parents. However, no definitely established effect on lung function has been seen in children, adults and asthmatics. The important question as to whether passive smoking increases lung cancer risk is still a subject of controversial discussion among experts. PMID- 2195522 TI - [General environmental pollutants: effect on at-risk groups]. AB - A number of epidemiologic studies have emphasized the relationship between air pollution and the frequency of respiratory symptoms in patients with underlying airway diseases. On the basis of acute controlled exposure studies, SO2 causes transient airflow obstruction in patients with asthma, but not necessarily in patients with bronchitis or lung fibrosis. The photochemical oxidants (ozone, NO2) induce an increase in airway responsiveness, ozone being of greater potential hazard than NO2. These effects have been described for healthy subjects and asthmatics. Acid aerosols may produce transient bronchoconstriction in asthmatics. In general, the harmful effects of polluted air will first affect the most sensitive persons in the population, such as asthmatics. PMID- 2195523 TI - [New occupational inhaled pollutants]. AB - New information about occupation-relative inhalative injuries, are reflected in the "Bill on the Modifications of the Regulations Governing Occupational Disease" of 22. 03. 1988; thus, for example, (benign) diseases of the pleura due to asbestos dust (No. 4103 and 4104), malignant neoplasias of the airways and lungs induced by nickel (No. 4109), and cooking plant gas (No. 4110), adenocarcinomas of the nasal sinuses, induced by oak and beech wood dust (No. 4203), exogenous allergic alveolitis, also those induced by other than agricultural dusts (No. 4201) (3) have all undergone modification. Current occupationalmedical problems represented in more detail include the hairdressers' asthma induced by hair bleaching agents, bronchopulmonary diseases induced by cooling and lubricating agents, "metal fume fever", asthma induced by enzyme dusts, flour and baking additives, bronchopulmonary and systemic diseases induced by acid anhydrides and isocynates. PMID- 2195524 TI - [Indications for artificial ventilation in status asthmaticus, adult respiratory distress syndrome and pneumonia]. AB - Mechanical ventilation is indicated in acute respiratory failure, especially in so-called pump failure as occurs in status asthmaticus, pneumonia and ARDS due to respiratory muscle fatigue. Using clinical parameters (inspiratory paradox, respiratory alternans), together with blood gas analysis and chest X-ray morphology, the indication can be established on a rational basis. The aims of therapy are tissue oxygenation and cure of the underlying disease which has led to respiratory failure. By adapting ventilator settings to the respiratory mechanics of the individual patient, complication due to barotrauma can be avoided. Respiratory muscle rest can be assessed by monitoring tracheal pressure time curves. Unconventional methods using very small t idal volumes and very high frequency so far have no clearcut indications, as they are still investigational. PMID- 2195525 TI - [Lung diseases following organ transplantation]. AB - The immune suppression required after organ transplantation is accompanied by an elevated risk of infection by conventional and opportunistic pathogens. The lungs are the organs that are most commonly affected. Following transplantation of the kidney, pulmonary diseases have dropped from 23% to less than 5%. After bone marrow grafting, bacterial pneumonia, fungal pneumonia, bronchitis, mixed bacterial and fungal pneumonia, interstitial viral pneumonia, unclear pulmonary infiltrates, idiopathic interstitial pneumonia, pneumonia due to rare pathogens, obstructive bronchitis, and ARDS can occur. CMV pneumonia can be avoided by immunoglobulin prophylaxis, the use of CMV-negative leukocyte free blood - and platelet transfusions. The CMV pneumonia occurs as a result of a lymphocytic reaction. Obstructive bronchiolitis is probably caused by activated lymphocytes following bone marrow grafting, via the graft-versus-host reaction, and following heart-lung transplantation by the rejection reaction. PMID- 2195526 TI - [Lung transplantation]. AB - Following the publication of the first positive results and follow-ups achieved with heart-lung and lung transplants in the United States of America, a joint pneumology/thoracic surgery working group "lung transplantation" was set up in our hospital. The following article presents our lines of thought on the indications governing the various methods, on the technique of operation (including organ removal) and on the aftercare of lung transplant patients, described in a summarising review that also includes the procedure followed by comparable centres. We are also reporting on the first surgical interventions carried out by us. PMID- 2195527 TI - Do anticytoplasmic autoantibodies (ACPA) extend our understanding of the spectrum of Wegener's granulomatosis? PMID- 2195528 TI - [Effects of intravenous prostaglandin E1 on bronchial histamine reactivity]. AB - The effects of infusion of different doses of prostaglandin E1 (12.5, 25, 50 ng kg-1 min-1) on airway responsiveness to inhaled histamine dichloride were observed in 16 subjects with normal and high bronchial reactivity. Subjects were randomized to receive PGE1 or placebo within an interval of three days. Normal saline was infused on one day and PGE1 on the other days. 10 minutes after starting the PGE1 infusion bronchial provocation was induced by histamine aerosol challenge. The provocation concentration of histaminedihydrochloride causing a 50% increase in bronchial resistance increased from 0.36 +/- 0.12 to 0.57 +/- 0.19 mg/ml in hyperreactive subjects (n.s.) and from 0.77 +/- 0.12 to 1.57 +/- 0.19 mg/ml in normal subjects (beta less than 0.05) after administration of 50 ng kg-1 min-1 PGE1 (p less than 0.05). Partial flow rates measured at maximal bronchoconstriction increased dose-dependently during the infusion of PGE1 (p less than 0.05). We conclude that intravenous administration of PGE1 partially protects against histamine-induced bronchoconstriction. In hyperreactive subjects PGE1 selectively increases flow at low lung volumes indicating an action on peripheral bronchial resistance. PMID- 2195529 TI - [Bronchoplastic surgery in bronchial cancer]. AB - Conservative resection is applied in cases with central localisation of the tumour in the surrounding lymph nodes are not affected by the malignant process. This surgery is of great importance for patients with restricted respiratory function if pneumonectomy is contraindicated or is performed under enhanced risk. A total of 29 surgeries were performed on the bronchial system. Blood vessel resection was simultaneously done in two of the cases. Frozen section biopsy was obligatorily performed. In one case atelectasis was an early complication that was resolved by bronchoaspiration. In a thirty-day long postoperative period one (3.4%) of the patients died because of profound intrathoracic bleeding. PMID- 2195530 TI - [Pulmonary blastoma. Immunohistochemical characterization of heteromorphic tumor components]. AB - The reaction pattern found in thirteen different pulmonary blastomas was tested with four different polyclonal and six different monoclonal antibodies using the avidin-biotin-reaction. Immunohistochemically, the tumours showed positive reactions, both with antibodies that are considered to be epithelial markers (K11, EMA), and with antibodies that indicate a differening mesenchymal differentiation (vimentine, desmine, protein-S100). It was not possible to label any tumour cells with the antibodies anti-beta-HCG, anti-NSE, anti-lysozyme or anti-CEA. The negative response of the CEA reaction can be useful for the differentiation from pulmonary adenocarcinoma, in particular in the case of tumours with highly differentiated glandular components. PMID- 2195531 TI - [Leu-M1, CEA and intermediate filament proteins in histochemical differential diagnosis of malignant pleural mesothelioma]. AB - The differential diagnosis "pleuramesothelioma" vs "metastatic adenocarcinoma" can mostly not be decided clearly by conventional histological methods in malignant pleuraneoplasias. Leu-M1 is employed in immunhistochemical diagnosis of lymphomas in Hodgkin's disease but it also reacts with adenocarcinoma cells. Pleuramesotheliomas are Leu-M1 negative. Intermediary filament proteins, CEA and Leu-M1 are important "markers" in the diagnosis of malignant pleuraneoplasias. 25 pleura biopsies of malignant pleura processes were subjected to immunhistochemical examination. PMID- 2195532 TI - [Methodologic comparison of the polyfrequency oscillation method, transcutaneous oxygen pressure measurement and body plethysmography in bronchial provocation with methacholine]. AB - A bronchial provocation challenge test was conducted with 30 subjects using metacholin. In randomised sequence lung function analysis tests were carried out with the bodyplethysmograph (Raw, FEV1) and the polyfrequent oscillation method (resistance, reactance between 2 and 52 Hz), whereas the transcutaneous oxygen pressure (tc-PO2) was measured continuously. Correlations between the various parameters, the change of the values at PD60 sGaw in relation to the initial values, the interindividual variability and the reactivity were determined. Medium correlations were found for the oscillatory parameters and Raw, whereas for tc-PO2 and Raw the correlation was markedly lower. In terms of percentage the greatest change was found in reactance, in relation to the initial value, followed by Raw and FEV1. The interindividual variability resulted in the highest values for the reactance, followed by Raw and FEV1. Interindividual variability showed the highest values for the reactance before oscillatory resistance and Raw. In respect of reactivity, reactance also had the highest values. Overall evaluation showed that bodyplethysmography and the polyfrequent oscillation method (reactance or resonance frequency) are comparably sensitive. PMID- 2195534 TI - [Clinical use of an expert system for interpreting lung function tests--relation of results to the respective examiner]. AB - We used a new expert system for interpretation of lung function tests to check the differences between four investigators. The data base of the program system consists of vectors which yield statistical informations concerning the decisions of the users. PMID- 2195533 TI - [A computerized processing unit for ambulatory diagnosis of sleep apnea and nocturnal hypoxemia]. AB - A new mobile device for the evaluation of the sleep-apnoea-syndrome in outpatients prior to conventional polysomnography, processes and stores the oronasal airflow detected by a thermistor, and the heart rate and oxygen saturation in a microprocessor unit. The major problem in on-line data processing of these variables is the interpretation of the thermistor signal for correct apnoea detection. This preliminary study investigates the reliability of the computer algorithm by control of the automatic airflow assessment. With a sensitivity of 97.3% the algorithm proved to be extreme reliable. Combined with the detection of heart rate and oxygen saturation it provides the capacity for comprehensive analysis of cardiorespiratory events and appears to be suitable for application in an outpatient setting. PMID- 2195535 TI - An assessment of the value of BCG vaccination in England and Wales. AB - The scheme for BCG vaccination at about age 13 years in England and Wales was introduced in 1953. The coverage of the scheme is now 75%, and the efficacy of BCG has been 75-80% throughout, but the incidence of tuberculosis in young white adults has been decreasing steeply since 1950. The benefits of the scheme have consequently been decreasing equally rapidly in recent years. Discontinuation of the scheme would lead to some additional cases of tuberculosis but would not greatly increase the very small current risk of tuberculosis developing in the unvaccinated 13-years old. PMID- 2195536 TI - [Long-term use of asynchronous independent lung ventilation: effects on gas exchange and hemodynamics]. AB - In three patients with respiratory insufficiency where conventional respiratory methods failed, PEEP, rate of breathing, and total volume were adjusted independently for each lung up to a period of 13 days, using two respirators and a double-lumen tube. In all patients a marked increase in PaO2 was achieved without any noticeable detrimental haemodynamic effects. We conclude that asynchronous independent lung ventilators can be a safe and useful respiratory method in carefully selected patients suffering from predominantly unilateral pulmonary disease in whom conventional respiration methods have failed; that synchronisation of the respiratory circuits is not necessary; and that AILV compared to SILV offers the advantage of greater flexibility and reduced complexity. PMID- 2195537 TI - [Pneumonia in AIDS: pathogen spectrum and diagnostic value of various fiberoptic bronchoscopy methods for the detection of pathogens]. AB - 39 fibre-bronchoscopic examinations were performed prospectively in 29 AIDS patients with pneumonia. Specimens were obtained from the central bronchial system with a protected brush and by suction, from the infiltrated peripheral area by catheter suction, protected brush, bronchoalveolar lavage (BAL) and transbronchial biopsy in randomized order. In patients with non-bacterial pneumonia, pneumocystis carinii (n = 20) was the most frequent pathogen. In this group BAL had a significantly higher rate of pathogen detection than other techniques. In patients with bacterial pneumonia (n = 10) the pathogens were found in all cases by suction from the central bronchial system. Fibre bronchoscopy in patients with AIDS and pneumonia should include specimens from the central bronchial system and a bronchoalveolar lavage. PMID- 2195538 TI - [Respiration and the body in family and academic medicine in early modern times]. PMID- 2195539 TI - [Hydrolysis and absorption of carbohydrates and correction of their disorders in patients with pulmonary tuberculosis]. AB - Characteristic features of hydrolysis and carbohydrate absorption in 106 newly diagnosed pulmonary tuberculosis patients were studied by means of a combined carbohydrate load method. Certain ways of treating the disturbances were tested. It was found that in 60% of the cases with an active pulmonary tuberculosis and with symptoms of gastrointestinal diseases, there were disturbed processes of hydrolysis and carbohydrate absorption. A long-term administration of antituberculous drugs affects hydrolysis and carbohydrate absorption in the small intestine. A chemotherapeutic regimen supplemented with insulin, glucocorticoids, and folic acid, in particular, leads to the improvement of hydrolysis and carbohydrate absorption in pulmonary tuberculosis patients. PMID- 2195540 TI - [A.E. Rabukhin--a scientist, physician and teacher]. PMID- 2195541 TI - Cardiovascular nursing research review. 1969 to 1988. AB - In a review of 243 cardiovascular nursing research articles, eight themes of cardiovascular nursing research have emerged: health related behaviors, activity, cardiac output, family, adherence, patient education, stress-anxiety coping, and perception of care and treatment. Several conclusions are drawn from this review. First, the quantity of cardiovascular nursing research in the literature during 1985-1988 has more than doubled from the number of articles published during 1981 1984. Second, cardiovascular nursing researchers are following earlier recommendations to engage in theory-then-research to build a scientific basis for nursing practice. Third, the topical trends identified in this review are congruent with priorities in nursing research established by the American Nurses' Association Cabinet on Nursing Research and the National Center for Nursing Research. Further suggestions for cardiovascular nursing research in the areas of technological dependency (such as implantable defibrillators) and individual and family responses (such as risk factor modification strategies in children, and behavioral responses to cardiovascular disease in the elderly and chronically ill) are proposed. PMID- 2195542 TI - Frameshift errors initiated by nucleotide misincorporation. AB - Studies presented here on the fidelity of DNA synthesis in vitro support the hypothesis that a classical base-substitution intermediate (i.e., a misincorporated nucleotide) can yield a frameshift mutation. By using a fidelity assay specifically designed to detect minus-one-base errors, nucleotide substrate pool imbalances that have previously been shown to increase the rate of misincorporation are now shown to also increase minus-one-base frameshift error rates. Examination of the specificity of the errors produced in reactions with various dNTP pool imbalances and various DNA templates revealed that template nucleotides were preferentially lost when they had as a 5' neighbor a nucleotide complementary to the dNTP provided in excess. This suggests that when a misincorporated nucleotide is complementary to the next nucleotide in the template, a misaligned intermediate containing a correct terminal base pair can form and be extended by a DNA polymerase, leading to a frameshift mutation. We present evidence that the proposed mechanism may operate in vivo and discuss the implications of this model for frameshift mutations induced by DNA damage. PMID- 2195543 TI - CD4-T-cell antigen receptor complexes on human leukemia T cells. AB - CD4 and T-cell antigen receptor (TCR) comodulate from the surface of human and murine T cells following exposure to monoclonal anti-CD4 or anti-TCR. This comodulation may occur because expression of CD4 and TCR is regulated by similar transmembrane signals or because CD4 and TCR are physically associated. To study multimolecular assemblies on the plasma membrane, we developed a flow cytometric method for detecting singlet-singlet energy transfer between fluorescein isothiocyanate (FITC)- and tetramethylrhodamine isothiocyanate (TRITC)-conjugated monoclonal antibodies as sensitized TRITC emission on intact, single cells. Using this procedure, we detected CD4-TCR complexes on the surface of the transformed human leukemia T cells, HPB-ALL, in the absence of stimulation. More than one CD4 were found in association with one TCR. CD4-TCR complexes were not in rapid equilibrium with free CD4 and free TCR, and they were not induced by the dye labeled anti-CD4 or anti-TCR. PMID- 2195544 TI - Islet amyloid polypeptide: pinpointing amino acid residues linked to amyloid fibril formation. AB - Islet amyloid polypeptide (IAPP), a putative polypeptide hormone, is a product of pancreatic beta-cells and the major constituent of the amyloid deposits seen mainly in islets of type 2 diabetic humans and diabetic cats. The connection between IAPP amyloid formation and diabetes is unknown, but a limited segment of the IAPP molecule, positions 20-29, seems responsible for the aggregation to fibrils. Differences in the amino acid sequence of this region probably determine whether or not islet amyloid can develop in a particular species. Amyloid fibril formation can be mimicked in vitro with the aid of synthetic peptides. With this technique we show that peptides corresponding to IAPP positions 20-29 of human and cat, species that develop IAPP-derived islet amyloid, form amyloid-like fibrils in vitro. The corresponding IAPP segment from three rodent species that do not develop IAPP-derived amyloid did not give rise to fibrils. Substitution of the human IAPP-(20-29) decapeptide with one or two amino acid residues from species without islet amyloid generally reduced the capacity to form fibrils. We conclude that the sequence Ala-Ile-Leu-Ser-Ser, corresponding to positions 25-29 of human IAPP, is strongly amyloidogenic and that a proline-for-serine substitution in position 28, as in several rodents, almost completely inhibits formation of amyloid fibrils. PMID- 2195545 TI - Intercalators promote the binding of RecA protein to double-stranded DNA. AB - Ethidium bromide, acridine orange, 4'-(9-acridinylamino)methanesulfon-o-anisidide (o-AMSA), and m-AMSA induce the rapid binding of RecA protein to double-stranded (ds) DNA. The filaments formed appear to retain the drug and are 12.8 nm in diameter with an 8.0-nm pitch. Two classes of drugs have been distinguished: (i) those that bind to RecA protein and induce assembly at low relative concentrations (e.g., ethidium bromide) and (ii) those that do not appear to interact directly with RecA protein and must be present at relatively high drug concentrations to stimulate assembly (e.g., m-AMSA). Ethidium bromide, acridine orange, and quinacrine inhibit RecA protein binding to single-stranded DNA. Addition of ATP to the drug-induced filaments causes the protein to rapidly dissociate from dsDNA, and protein binding to dsDNA diminishes upon extended exposure to room light. We suggest that the structure of the drug-induced filaments may be more typical of the complex that initiates RecA protein assembly along DNA rather than the product of extensive polymerization as induced by adenosine 5'-[gamma-thio]triphosphate. PMID- 2195546 TI - Beta-glucoside permease represses the bgl operon of Escherichia coli by phosphorylation of the antiterminator protein and also interacts with glucose specific enzyme III, the key element in catabolite control. AB - The beta-glucoside (bgl) operon of Escherichia coli is subject to both positive control by transcriptional termination/antitermination and negative control by the beta-glucoside-specific transport protein, an integral membrane protein known as enzyme IIBgl. Previous results led us to speculate that enzyme IIBgl exerts its negative control by phosphorylating and thereby inactivating the antiterminator protein, BglG. Specifically, our model postulated that the transport protein enzyme IIBgl exhibits protein-phosphotransferase activity in the absence of beta-glucosides. We now present biochemical evidence that the phosphorylation of protein BglG does indeed occur in vivo and that it is accompanied by the loss of antitermination activity. BglG persists in the phosphorylated state in the absence of beta-glucosides but is rapidly dephosphorylated when beta-glucosides become available for transport. Our data also suggested specific interactions between the beta-glucoside transport protein and the glucose-specific enzyme III (enzyme IIIGlc), a component of glucose transport and a key element in regulation of catabolite repression. These observations indicate that enzyme IIIGlc may, in conjunction with enzyme IIBgl, modulate the transport of beta-glucosides and the phosphorylation of the antiterminator protein. In the absence of both sugars, when the catabolite controlled promoter of the operon is derepressed, enzyme IIIGlc may mediate tight repression of antitermination. PMID- 2195547 TI - A transdominant tat mutant that inhibits tat-induced gene expression from the human immunodeficiency virus long terminal repeat. AB - Regulation of human immunodeficiency virus (HIV) gene expression is dependent on specific regulatory regions in the long terminal repeat. These regions include the enhancer, SP1, "TATA," and trans-activating (TAR) regions. In addition, viral regulatory proteins such as tat and rev are important in regulating HIV gene expression. The mechanism of tat activation remains the subject of investigation, but effects at both transcriptional and posttranscriptional levels seem likely. Previous mutagenesis of the tat protein revealed that the amino terminus, the cysteine-rich domain, and the basic domain were all required for complete tat activation. Mutants of other viral trans-acting regulatory proteins, including E1A, tax, and VM65, have been identified that were capable of antagonizing the activity of their corresponding wild-type proteins. We wished to determine whether mutants of the tat protein could be identified that exhibited a similar phenotype. One mutant (delta tat) that truncated the basic domain of tat resulted in a transdominant phenotype inhibiting tat-induced gene expression of the HIV long terminal repeat but not other viral promoters. This mutant exhibited its maximal phenotype in cotransfection experiments when present in an 8- to 30-fold molar excess over the wild-type tat gene. Trans-activation of the HIV long terminal repeat by delta tat was very defective at the DNA concentrations used in these experiments. RNase protection analysis indicated that this mutant decreased tat-induced steady-state mRNA levels of the HIV long terminal repeat. Second-site mutations of the delta tat gene in either the amino terminus or cysteine region eliminated the transdominant phenotype. In contrast to tat, which was localized predominantly to the nucleolus, delta tat was present in both the nucleus and cytoplasm, suggesting that it may inhibit tat function by preventing nucleolar localization. Transdominant mutants of tat may have a role in potentially inhibiting HIV gene expression. PMID- 2195548 TI - Transfer of a yeast artificial chromosome carrying human DNA from Saccharomyces cerevisiae into mammalian cells. AB - To test the feasibility of transferring yeast artificial chromosomes (YACs) into mammalian cells, we modified a YAC that carries approximately 450 kilobases (kb) of human DNA, by inserting a neomycin-resistance gene. Saccharomyces cerevisiae cells carrying this YAC were fused by polyethylene glycol to mouse L cells and G418-resistant colonies were obtained. A high percentage of these clones contained virtually intact YAC sequences as revealed by "Alu fingerprint" analysis and restriction enzyme analysis using pulsed-field gel electrophoresis. Furthermore, the YAC sequences were stably integrated into the mouse chromosomes, as shown by in situ hybridization and by the stability of the G418 resistance. These results establish that large segments of the mammalian genome, cloned in yeast, can be efficiently transferred into cultured mammalian cells. PMID- 2195550 TI - Generation of transgenic mice with elevated blood pressure by introduction of the rat renin and angiotensinogen genes. AB - The role of the renin-angiotensin system in blood pressure control and in the development of hypertension was investigated by generating transgenic mice carrying the rat renin or angiotensinogen gene or both genes under the control of the mouse metallothionein I promoter. The systolic blood pressure was significantly elevated in transgenic mice carrying both transgenes but was maintained normally in those bearing either of the transgenes. The transgene was effectively and properly transcribed to form the mature mRNA in the transgenic mice. The production of rat renin and angiotensinogen in the transgenic mice carrying the corresponding transgene was also verified by immunoanalyses of these proteins. Furthermore, the specific angiotensin-converting enzyme inhibitor captopril was effective in reducing the elevated blood pressure of the hypertensive transgenic mice. These results indicate that the combined action of the exogenous rat renin and angiotensinogen is responsible and necessary for elevation of blood pressure in the hypertensive transgenic mice. PMID- 2195549 TI - Human homolog of fission yeast cdc25 mitotic inducer is predominantly expressed in G2. AB - Entry into mitosis during the somatic cell cycle is regulated in response to signals that monitor the completion of DNA replication, the integrity of the nuclear genome, and, possibly, the increase in cellular mass during the cell cycle. It has been postulated that the operation of this cell cycle control involves the gradual accumulation of rate-limiting mitotic inducers, which trigger nuclear division when their cellular concentration reaches a critical level. We have cloned a human gene, which we call CDC25, whose product may function as a mitotic inducer. This human gene encodes a protein with a predicted molecular mass of 53,000 daltons whose C-terminal domain shares about 37% sequence identity with the fission yeast cdc25+ mitotic inducer. The human CDC25 gene rescues the defect of a fission yeast temperature-sensitive (ts) cdc25ts mutant that is unable to initiate mitosis. In HeLa cells CDC25 mRNA levels are very low in G1 and increase at least 4-fold as cells progress towards M phase. These data suggest that in human cells, as in fission yeast, the accumulation of CDC25 mitotic inducer during G2 may play a key role in regulating the timing of mitosis. PMID- 2195552 TI - The roles of DNA polymerases alpha and delta in DNA replication. AB - The identities and precise roles of the DNA polymerase(s) involved in mammalian cell DNA replication are uncertain. Circumstantial evidence suggests that DNA polymerase alpha and at least one form of DNA polymerase delta, that which is stimulated by Proliferating Cell Nuclear Antigen, catalyze mammalian cell replicative DNA synthesis. Further, the in vitro properties of polymerases alpha and delta suggest a model for their coordinate action at the replication fork. The present paper summarizes the current status of DNA polymerases alpha and delta in DNA replication, and describes newly available approaches to the study of those enzymes. PMID- 2195551 TI - Enhancement of the antitumor effects of 5-fluorouracil by folinic acid. AB - Although 5-fluorouracil (FUra) is one of the most effective cytotoxic agents in the treatment of various solid tumors (carcinomas of the gastro-intestinal tract, breast, head and neck), remissions occur in only 20-30% of cases and usually are of short duration. Recently, preclinical studies have shown that the antitumor activity of FUra can be potentiated by modulating the metabolism of this drug by using other substances, in particular 5-formyltetrahydrofolate (folinate, LV). Reduced folates (LV and 5-methyltetrahydrofolate) at concentrations greater than or equal to 1 microM can, by raising the intracellular levels of 5,10 methylenetetrahydrofolate, increase and prolong the inhibition of the target enzyme, thymidylate synthase, with formation of a stable ternary complex formed by the enzyme, the folate coenzyme and the fluoropyrimidine inhibitor (5 fluorodeoxyuridylate). After phase II clinical trials reported encouraging results with the combination LV-FUra in the treatment of patients with various solid tumors, randomized controlled studies in patients with colorectal carcinoma have documented an increase in the response rate of the combination compared to treatment with FUra alone. The integration of the LV-FUra combination into multidrug regimens is now under investigation for the treatment of carcinomas of the breast, stomach, and head and neck. PMID- 2195553 TI - Role of glutathione in the radiation response of mammalian cells in vitro and in vivo. AB - Radiation interacts with biological systems to produce many types of molecular lesions. Much of the molecular damage is of little consequence with regard to cell killing. The lesions that are most likely to contribute to cell killing are DNA lesions produced by clusters of radicals. The formation of clusters of radicals is characteristic of ionizing radiation and accounts for its high efficiency as a cytotoxic agent. The mechanism by which these lesions kill cells is probably the formation of DNA double-strand breaks, ultimately resulting in chromosomal breaks. There is a possibility that some of the other types of molecular lesions produced by radiation may participate in more subtle mechanisms of cell damage. For instance, radiation induces a self-destructive process (apoptosis) in certain cell types, and the molecular lesions that initiate this process have not been identified. Glutathione (GSH) is a versatile protector. Several distinct mechanisms of radioprotection by GSH can be identified. These include radical scavenging, restoration of damaged molecules by hydrogen donation, reduction of peroxides and maintenance of protein thiols in the reduced state. Of these mechanisms, hydrogen donation to DNA radicals is probably the most important. Since competing reactions are very rapid, this mechanism requires a high concentration of GSH. Radioprotection by hydrogen donation to DNA radicals is not effective in oxygenated cells because the normal intracellular GSH concentration is not sufficient for effective competition with oxygen. Consequently, moderate depletion of GSH has no effect on the radiosensitivity of oxygenated cells. Under hypoxic conditions GSH becomes more competitive, and GSH depletion can markedly affect radiosensitivity. The radiosensitivity of hypoxic cells is most affected by GSH depletion in the presence of low concentrations of radiosensitizers. Since hypoxic cells are a characteristic feature of tumors, moderate depletion of GSH in combination with treatment with hypoxic cell radiosensitizers appears to be a promising strategy for selective tumor sensitization in radiation therapy. Oxidation of GSH can result in radiosensitization of both hypoxic and oxygenated cells. The mechanism of this effect appears to involve oxidation of protein thiols which are important for DNA repair. In principle, modification of DNA repair could have a greater impact on radiation therapy than modification of the number of lesions produced by radiation. However, a strategy for modification of GSH or protein thiol redox state in vivo has not yet been devised. PMID- 2195554 TI - Metabolism and pulmonary toxicity of cyclophosphamide. AB - Pulmonary toxicity caused by an antineoplastic drug, cyclophosphamide is becoming a more frequently recognized entity. Metabolism of cyclophosphamide in lung to alkylating metabolites and acrolein, a reactive aldehyde are in part responsible for pulmonary toxicity. Alterations in pulmonary mixed-function oxidase activity, glutathione content, and microsomal lipid peroxidation may be caused by the reactive metabolite acrolein. Potentiation of cyclophosphamide-induced pulmonary injury under hyperoxic conditions is caused by depression of pulmonary antioxidant defense mechanisms by cyclophosphamide and its other metabolites but not acrolein. Cyclophosphamide- and acrolein-induced alterations in the physical state of membrane lipid bilayer may be the major cause of inactivation of membrane-bound enzymes. These data suggest that cyclophosphamide and its reactive metabolites initiate peroxidative injury resulting in alterations in the physical state of membrane lipids which may be functionally linked to manifestations of cyclophosphamide-induced pulmonary toxicity. PMID- 2195555 TI - Effects of psychotropic drugs on the behavior and neurochemistry of olfactory bulbectomized rats. AB - Since its first characterization as a model for the detection of antidepressant drugs (van Riezen et al., 1976) a large body of data now supports the view that olfactory bulbectomy produces changes in animal behavior that are reversed by chronic treatment with antidepressants. The behavioral deficits seen in olfactory bulbectomized rats (such as irritability, deficits in acquisition of avoidance and of appetitive motivated conditioning and hyperactivity in a new environment) are probably the results of a reduced ability to adapt to environmental changes. These behavioral changes, their biochemical consequences and the effects of treatments with psychotropic drugs are reviewed. These studies suggest that the olfactory bulbectomized rat is a model of depression useful to detect antidepressant drugs. PMID- 2195556 TI - Genetic variants of human serum cholinesterase influence metabolism of the muscle relaxant succinylcholine. AB - People with genetic variants of cholinesterase respond abnormally to succinylcholine, experiencing substantial prolongation of muscle paralysis with apnea rather than the usual 2-6 min. The structure of usual cholinesterase has been determined including the complete amino acid and nucleotide sequence. This has allowed identification of altered amino acids and nucleotides. The variant most frequently found in patients who respond abnormally to succinylcholine is atypical cholinesterase, which occurs in homozygous form in 1 out of 3500 Caucasians. Atypical cholinesterase has a single substitution at nucleotide 209 which changes aspartic acid 70 to glycine. This suggests that Asp 70 is part of the anionic site, and that the absence of this negatively charged amino acid explains the reduced affinity of atypical cholinesterase for positively charged substrates and inhibitors. The clinical consequence of reduced affinity for succinylcholine is that none of the succinylcholine is hydrolyzed in blood and a large overdose reaches the nerve-muscle junction where it causes prolonged muscle paralysis. Silent cholinesterase has a frame shift mutation at glycine 117 which prematurely terminates protein synthesis and yields no active enzyme. The K variant, named in honor of W. Kalow, has threonine in place of alanine 539. The K variant is associated with 33% lower activity. All variants arise from a single locus as there is only one gene for human cholinesterase (EC 3.1.1.8). Comparison of amino acid sequences of esterases and proteases shows that cholinesterase belongs to a new family of serine esterases which is different from the serine proteases. PMID- 2195557 TI - Glutathione-dependent protection against oxidative injury. AB - Functions of GSH in detoxication during radical-induced injury in specific pathological and toxicological conditions are discussed. GSH protects against oxidative damage in systems that scavenge radicals, eliminate lipid peroxidation products, preserve thiol-disulfide status of proteins, and repair oxidant damage. Several factors which affect cellular GSH homeostasis can affect these functions, including nutritional status, hypoxia and pharmacological intervention. Evidence from a variety of pathological and toxicological conditions, e.g. ischemia reperfusion injury, chemically induced oxidative injury, radiation damage, aging, and degenerative diseases, indicate that GSH is a primary component of physiological systems to protect against oxidant and free-radical-mediated cell injury. PMID- 2195558 TI - Histamine receptors: subclasses and specific ligands. AB - In this review the three main types of histamine receptors are discussed together with their specific ligands. For the classical H1-receptors much emphasis is put on the mechanism by which the receptor is stimulated. For the H1- and H2-receptor the review includes information on the several models available for establishing agonistic or antagonistic activity. In the section on the H3-receptor the ligands are discussed as well as the possible physiological role of this receptor. In the final paragraphs some less well defined activities are presented. PMID- 2195559 TI - Separation of left and right skull bones from low angle x-ray projections. AB - This study shows how two layers which are superposed in two low angle x-ray projections can be reconstructed separately without having any a priori knowledge of their shape. Similar to stereoscopic imaging, the projections of the two layers appear at different positions in the two superposition images. Matching one of the layers allows its elimination by subtraction. The resulting difference signal is the so-called 'movement artefact' of the second, mismatched layer. A filter method is developed to reconstruct this layer from the spectrum of its artefact within the Fourier domain. The second layer is reconstructed in an analogous way. So, for example, the bones of the left and the right side of the human skull can be imaged separately. This is used to reduce image artefacts caused by patient movements in subtraction angiography and tumourfluoroscopy of the brain. PMID- 2195560 TI - Isolation and characterization of a subunit form of the B875 light-harvesting complex from Rhodobacter capsulatus. AB - A structural subunit (called B816) has been isolated from the B875 light harvesting complex of Rhodobacter capsulatus using a detergent-mediated dissociation of chromatophores. Rb. capsulatus MW442 (B800-850- B875+ car+) chromatophores were extracted with benzene and titrated with octyl glucoside (OG) to shift the near-infrared absorption maximum from 873 to 816 nm. Gel filtration chromatography was then used to separate B816 from reaction centers. B816 could be quantitatively shifted back to a B875-like form (lambda max = 875 nm) by decreasing the OG concentration. A similar B816 species could be isolated in low yield from wildtype (B800-850+ B875+ car+) cells but not from SB203E (B800-850- B875+ car-). In the latter case, the B816 subunit seemed too unstable to be isolated under equivalent conditions. The alpha:beta polypeptide ratio, the CD spectrum, and the ability to reversibly dissociate B816 to free bacteriochlorophyll and alpha- and beta-polypeptides were found to be similar to those of the B820 subunit of Rs. rubrum previously reported by our laboratory. PMID- 2195561 TI - Temperature dependence of tryptophan phosphorescence in proteins. AB - The phosphorescence yield and decay kinetics of tryptophan (Trp) in apoazurin from Pseudomonas aeruginosa, subtilisin Carlsberg, Staphylococcal nuclease and liver alcohol dehydrogenase were determined as a function of temperature from 150 K (glassy matrix) to 300 K (fluid solution). The constancy of the lifetime normalized phosphorescence yield with apoazurin and with Trp-314 in alcohol dehydrogenase establishes that the intersystem crossing quantum yield is practically unaffected across the temperature range. Consequently, any decrease in phosphorescence intensity not accounted for by lifetime-shortening is a signal either of the selective quenching of specific Trp residues in the same macromolecule or that the protein sample is heterogeneous in its emission properties. From an analysis of the thermal profile it is concluded that subtilisin Carlsberg and S. nuclease, as opposed to apoazurin, are not phosphorescent at ambient temperature, their residual emission probably arising from protein impurities. Criteria for distinguishing conformer emission from a contribution by protein impurities are discussed. PMID- 2195562 TI - Transient and time-resolved optical studies of photolyzed carbonmonoxy hemoglobin and myoglobin. PMID- 2195563 TI - The UvrABC endonuclease of Escherichia coli. PMID- 2195564 TI - Sunlight and cutaneous malignant melanoma: evidence for and against causation. PMID- 2195565 TI - Bright light therapy for winter depression: potential ocular effects and theoretical implications. PMID- 2195566 TI - Photoelectric measurements of purple membranes. PMID- 2195568 TI - Treatment of breast contractures with open capsulotomy and replacement of gel prostheses with polyurethane-covered implants. AB - Capsular contracture around gel and gel-saline implants is the most common complication following breast augmentation and reconstruction. Thirty-one patients with postaugmentation gel-implant contractures were treated with open capsulotomy and replacement with polyurethane-covered implants. Eighty-seven percent remain soft after a minimum follow-up of 14 months. Results of replacement after subcutaneous mastectomy and reconstruction are more varied and less successful. Results in 14 patients are presented. PMID- 2195567 TI - Preoperative antibiotics and capsular contracture in augmentation mammaplasty. AB - The main drawback with augmentation mammaplasty using implants is capsular contracture. The cause of this complication is still unknown. Silicone particles, hematoma, and bacterial contamination are some of the etiologic factors discussed. In this randomized, double-blind study on 76 breast-augmented women, 50 percent of the patients had preoperative prophylaxis with benzylpenicillin and dicloxacillin. Bacteria samples were taken intraoperatively. The number of negative cultures increased significantly with antibiotic prophylaxis. In four follow-ups during the first postoperative year, the rate of contractures was evaluated by subjective and objective methods. The results showed no statistically significant difference between the placebo and the antibiotic group with respect to the incidence of capsular contracture. PMID- 2195569 TI - Regional variations of laser Doppler blood flow in ischemic skin flaps. AB - An island skin flap was designed on the left inferior epigastric neurovascular bundle of anesthetized male rats. Blood flow was measured in situ with a laser Doppler flowmeter at 20 discrete points on a grid system (5 points in each quadrant of the flap) before and after surgery, or before vascular occlusion, during reperfusion, and 48 to 72 hours later. Two series of experiments were performed. In the first series, the raised flap was placed in a bath containing heated Ringer's solution and the left pedicle was cross-clamped. After 30 minutes, adenosine at a concentration that produced supramaximal vasodilatation, or its vehicle, was added to the bath. After 1 hour total occlusion time, the vascular clamp was released and adenosine treatment was continued for the first 30 minutes of reperfusion. In the second series, the protocol was similar except that adenosine, or its vehicle, was infused into the ischemic flap by means of the distal stump of the right inferior epigastric artery. After 48 to 72 hours, fluorescein was injected IV. The data showed a significant regional variation in baseline laser Doppler blood flow that was further altered by surgically raising the flap. Whereas proximal axial laser Doppler blood flow was essentially unchanged from the preoperative baseline, distal axial laser Doppler blood flow decreased 10 to 50 percent, and proximal and distal dependent laser Doppler blood flow decreased 50 to 80 percent. Thus no single value accurately reflected total flap perfusion. Necrosis occurred only in the dependent flap regions, which confirmed previous work. In the dependent regions, especially along the incision line, postoperative laser Doppler blood flow was lowest.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2195570 TI - Cutaneous ciliated cyst: case report and literature review. AB - An 18-year-old girl had a cyst excised from the left buttock in 1988. The cyst was diagnosed to be a cutaneous ciliated cyst, since histologic examination using special stains demonstrated its lining to be similar to fallopian tube epithelium. Only 20 such cases have been published to date, and this report is probably the first case in the plastic surgical literature, to the best of our knowledge. PMID- 2195571 TI - Platelet-mediated thrombosis in microvascular surgery: new knowledge and strategies. PMID- 2195572 TI - Long-term use of polyurethane breast prostheses: a 14-year experience. AB - I have used polyurethane prostheses for the past 14 years, implanting 220 implants into 130 patients who desired breast reconstruction after subcutaneous mastectomy or cancer ablation or simply breast augmentation. I theorize that a polyurethane-covered implant resists contracture, retaining its compressibility because the fibroblasts proliferate into the polyurethane in many different directions. When the fibrils contract, the forces of contracture counterbalance one another, resisting contracture. However, when smooth prostheses are implanted, fibrils are directed in a circular fashion around the implant and naturally contract, leading to firmer breasts. There were 115 prostheses inserted following subcutaneous mastectomy, and 22 percent developed contracted capsules. Seven implants became exposed because of skin necroses; one was removed because of a Staphylococcus infection; and two patients developed a combination of polyurethane and silicone granulomas. These developed only with the earlier implant, where there was shedding of the polyurethane sponge layer and silicone bled from the low-viscosity silicone used in the earlier implants. No granulomas were noted with the currently used Surgitek Replicon implant. Eighty-five breasts were reconstructed after cancer ablation with polyurethane implants, and the contracture rate was 2.3 percent. Other complications were minimal. A smaller group of patients had augmentation mammaplasty, and 20 prostheses were placed in 10 patients. A 15 percent contracture rate was noted in this group. In this study, 82 percent of patients were followed for up to 14 years. Capsular contractures occurred in 30 implants between 1 and 11 years, for an average recurrence at 6.3 years. The overall contracture rate was 13 percent. Other complications were minimal. All implants were placed subcutaneously or subglandularly, and all were drained. PMID- 2195573 TI - Circumferential reduction of areolar size. PMID- 2195574 TI - Use of a modified abdominal binder to prevent postoperative superior displacement of submusculofascial breast implants and expanders. PMID- 2195575 TI - Somatic and psychological symptoms during isoproterenol-induced panic attacks. AB - To determine which symptoms characterized isoproterenol-induced panic attacks, we analyzed the presence of panic attacks in 54 panic disorder patients who panicked, 24 patients who did not panic, and 37 controls who did not panic during isoproterenol infusions. The increases over the baseline of the symptoms shortness of breath and fear of going crazy were highly associated with panicking patients when compared to nonpanicking patients and nonpanicking controls. The increases of the symptoms trembling and shaking, generally nervous, and fear of going crazy were highly associated with patients when compared to controls. The possibility of a cognitive theory of panic attacks is discussed. PMID- 2195576 TI - Antidepressant or antianxiety? A study of the efficacy of antidepressant medication. AB - The authors analyzed the relative contributions of improvement in depressive and anxiety symptoms, as measured by the Hamilton Rating Scale for Depression (HRSD) and the Hamilton Rating Scale for Anxiety (HRSA), respectively, after 1 week of treatment to the prediction of improvement in HRSD score after 6 weeks of antidepressant pharmacotherapy. Fifty-six subjects completed 6 weeks of treatment with either desipramine (n = 20), alprazolam (n = 18), or a desipramine alprazolam combination (n = 18). The results showed that early improvement in the HRSD was a moderately strong predictor of the total 6-week improvement in HRSD score, and a better predictor than early improvement in the HRSA. Partial correlations showed that early HRSD improvement was significantly related to total HRSD improvement within the alprazolam group. This pattern of response differed from those observed for the other treatment groups. Desipramine-treated subjects showed gradual improvement over the course of the study, and the improvement in week 1 was not so strongly predictive of overall improvement. The relationship between early and total HRSD improvement for the combination treatment group was intermediate to the other two groups. These findings are discussed in the context of the relationship between depression and anxiety, and potential implications for the treatment of these overlapping and often mixed syndromes. PMID- 2195577 TI - Sleep, clonidine, and their interactive effect on growth hormone secretion in normal men. AB - Central alpha 2-adrenergic function is often inferred from the growth hormone (GH) response to clonidine, despite the drug's known hypnotic effect and the accepted cholinergic mechanism for sleep-related GH secretion. We examined the effect of daytime sleep on GH secretion in normal men taking placebo or clonidine orally, using a two-group blind design (placebo, clonidine; n = 9 each). Each subject participated in two morning sessions monitored by polysomnography: wake (sleep actively prevented) and sleep (subjects asked to sleep for 3 hr after receiving placebo or clonidine). Blood samples were drawn at times -15 min, 0, and every 30 min for 3 hr after the test dose was given. The total sleep time was similar for both groups. The placebo/wake group had lower GH responses than the other three groups. None of the GH responses in the clonidine/sleep group were significantly different from those in the placebo/sleep group; and the peak GH micrograms/L, mean +/- SD) was 16.9 +/- 10.9 vs. 14.6 +/- 10.5, respectively. We conclude that the GH response to clonidine may not be indicative of alpha 2 adrenergic function if sleep is permitted during the test. PMID- 2195578 TI - The endocrinology of transsexualism: a review and commentary. AB - Testicular hormones play a decisive role in the sexual differentiation of the genitalia. There is now also an impressive body of knowledge, gathered predominantly from laboratory animals, of the influence of gonadal steroid hormones on the prenatal/perinatal sexual differentiation of the brain. The well documented mechanisms in animals have been extrapolated, sometimes dogmatically, to the development of sexual orientation and gender identity/role in humans. In principle, it is doubtful that an animal model of human gender identity can be found. Studies in humans have shown that levels of circulating sex steroids and estrogen feedback on luteinizing hormone do not differ between transsexuals and controls. The only reliable sources of information on hormonal influences on human gender identity formation are clinical syndromes in which the hormonal environment of the fetus has been atypical. Follow-up studies of such patients have provided evidence for possible effects of prenatal sex steroids on brain lateralization, sexual orientation and gender role stereotypes. However, a straightforward hormonal effect on gender identity (self-identification as male or female) has been difficult to ascertain up to the present time. PMID- 2195579 TI - Caffeine effects on cardiovascular and neuroendocrine responses to acute psychosocial stress and their relationship to level of habitual caffeine consumption. AB - The effects of a moderate dose of caffeine on cardiovascular and neuroendocrine stress reactivity were examined in 25 healthy male subjects selected as habitual or light consumers of caffeine. Measurements were taken under resting conditions before and after administration of caffeine (3.5 mg/kg) or placebo, during a stressful laboratory task, and in a post-stress recovery period. Caffeine elevated blood pressure and plasma norepinephrine levels at rest, effects which added significantly to the effects of stress. Caffeine potentiated stress-related increases in plasma epinephrine and cortisol stress, more than doubling the responses observed in the control condition. These effects were present in both habitual and light consumers and level of habitual caffeine consumption did not affect their magnitude. Results indicate that caffeine can potentiate both cardiovascular and neuroendocrine stress reactivity and that the habitual use of caffeine is not necessarily associated with the development of tolerance to these effects. PMID- 2195580 TI - Blood pressure response to the "second cup of coffee". AB - Twenty young male coffee-drinkers consumed 150 mg of caffeine in decaffeinated coffee three times a day for 8 days. On days 3, 4, 7, and 8, caffeine or a placebo was administered in the laboratory at 11 A.M., 8 A.M., 11 A.M., and 8 A.M., respectively, in a randomized double-blind crossover design. There was a blood pressure increase relative to the placebo 45 min after taking caffeine at 8 A.M. (5.8/6.5 mm Hg). An increase of 2.4/5.2 mm Hg was seen with the second cup of coffee at 11 A.M. The lower the subject's pre-coffee serum caffeine level, the higher the systolic response, both at 8 A.M. (r = -0.60) and at 11 A.M. (r = 0.62). Because of the pressor effect resulting from habitual caffeine intake, the adverse implications of caffeine use should be considered. PMID- 2195581 TI - [Prostatic and bladder cancer--possibilities and limitations of diagnostic imaging]. AB - An optimal detection and subsequent documentation of tumour development with imaging methods is achieved with transrectal sonography combined with biopsy. In bladder carcinoma the penetration through the cystic wall and infiltration into adjacent organs and the lymph nodes is detected by computed tomography or better by magnetic resonance tomography. PMID- 2195582 TI - [A comparison of mammographic, sonographic and histologic parameters in breast cancer]. AB - Sonography provides a safety in dignity that is comparable to mammography while its overall sensitivity is higher. Mammography remains the method of choice. All mammographically unclear cases should be elucidated with sonography. For this reason an integration of a sonographic device and a mammography unit is advisable. PMID- 2195583 TI - [The beginnings of radiography in Leipzig. A contribution to the celebration of the 575th anniversary of the Leipzig Medical Faculty]. AB - The discovery of x-rays by Wilhelm Conrad Rontgen in 1895 immediately opened several fields of application in medicine. We attempt to demonstrate this development for the surgical applications of radiology at the medical faculty of Leipzig university. PMID- 2195584 TI - [Physics and technology of lithotripsy using extra- and intracorporeal generated shock waves]. AB - After a quantitative analysis of the number of patients with renal and biliary concrements in the GDR (1985: 17,000 and 67,000 hospitalizations) the principles of lithotripsy with extracorporally and intracorporally generated shock waves are described. The various principles of industrially manufactured devices (electric discharge, electromagnetic, piezoelectric, laser induced) are described including the associated methods for location of the concrements. Lithotripsy with extracorporally generated shock waves (ESWL) has replaced surgical removal of renal and urethral concrements and is increasingly used for biliary and pancreatic concrements. Intracorporally generated shock waves (often laser induced and therefore cheaper than ESWL) are used less frequently, but can replace surgery for salivary concrements. PMID- 2195585 TI - Stereotactic radiosurgery of arteriovenous malformations. AB - Stereotaxis has been introduced at the Joint Center for Radiation Therapy in Boston, MA, to aid in the precise localization and treatment of arteriovenous malformations (AVMs). A Brown-Roberts-Wells stereotactic system and a 6 MV linear accelerator have been modified for these treatments. By using multiple isocentric rotational fields, radiation doses from 1500 to 2500 cGy can be safely prescribed to the AVM in efforts to occlude the blood vessels without risking damage to nearby radiosensitive structures. Sixteen patients have been treated from February 1986 to July 1988 using the technique described. PMID- 2195586 TI - The history of humanism in the radiography essentials. AB - The need to emphasize humanism in medical and allied health curricula has become an issue in recent years because of the tremendous increase in technology. This article investigates the history of humanism in the radiography curriculum by reviewing the historical progression of the Essentials and Guidelines of an Accredited Program for the Radiographer. PMID- 2195587 TI - Bright echogenic foci in early prostatic carcinoma: sonographic and pathologic correlation. AB - One hundred sixty patients with biopsy-proved clinical stage A or B prostatic carcinoma were examined with high-resolution transrectal ultrasonography prior to radical prostatectomy. All tumors showed either a hypoechoic or isoechoic echo pattern. However, 11 patients demonstrated evidence of focal bright echogenic areas at the periphery or within the center of a hypoechoic tumor. Coarse echogenic foci seen in seven patients corresponded pathologically to calcified corpora amylacea in benign tumors of the prostate gland either at the edge of the tumor or scattered throughout the tumor. Seven patients showed a fine, stippled echogenic pattern within the lesion. On a pathologic level, this pattern represented high-grade tumors with extensive central comedonecrosis and calcifications in five patients and an unusual deposit of small intraluminal crystalloid deposits in two patients. Combinations of echo patterns were observed in three patients. This study demonstrates that echogenic foci can be seen within predominantly hypoechoic tumor nodules. Coarse bright echoes, usually at the periphery of the tumor, suggest calcifications in benign prostate glands. Tumor calcifications and intraluminal prostatic crystalloid deposits were located more centrally and had a finer stippled sonographic appearance. PMID- 2195588 TI - Value of random US-guided transrectal prostate biopsy. AB - One hundred sixty-four men underwent ultrasound-guided transrectal biopsy of a hypoechoic prostatic nodule suspicious for malignancy, and random biopsy of normal-appearing areas of the gland. The contribution of random biopsy to diagnosis, staging, and management of prostatic carcinoma was evaluated. A diagnosis of carcinoma was made in 71 patients (43.3%). Carcinoma was diagnosed at biopsy of only the nodule in 56 of these patients (79%), at both the nodule and random biopsy site in 10 (14%), and only at the random biopsy site in five (7%). Random biopsy did not result in significant alteration of clinical staging. However, management was altered in five patients with positive results at random biopsy only, four of whom underwent surgery. The additional yield from random prostatic biopsy was small but distinct and had clinical relevance. The authors conclude that random biopsy is a useful procedure in the evaluation of patients with prostatic nodules. PMID- 2195589 TI - Pelvic masses: aspiration biopsy with transrectal US guidance. AB - Biplanar, transrectal ultrasound guidance was used in the transrectal aspiration of two pelvic abscesses, one recurrent tumor, and one sterile, nonmalignant fluid collection. This method provides an alternative path that allows precise localization for aspiration biopsy of pelvic masses. PMID- 2195590 TI - Color Doppler US in the evaluation of acute scrotal disease. AB - Twenty-seven patients presented with painful acute scrotal swelling. After a clinical impression was established, all patients underwent diagnostic imaging with color Doppler ultrasound (US). Seven patients underwent surgical exploration for testicular torsion diagnosed with color Doppler US (100% operative confirmation), one underwent radical orchiectomy for treatment of seminoma, and one underwent orchidopexy for treatment of a freely mobile testis. Eighteen patients were treated for nonoperable conditions. Diagnoses made with color Doppler US correlated with final clinical diagnoses in all patients. In 10 of 27 patients (38%), the diagnosis was established at color Doppler US. Until now, nuclear scanning has had a paramount role in the evaluation of equivocal cases of acute scrotal disease. Results show that color Doppler US helps accurately correlate anatomy and perfusion in real time and may prove to be the definitive imaging technique for the diagnostic evaluation of acute scrotal pain or swelling. PMID- 2195591 TI - Pseudogestational sacs: Doppler US differentiation from normal or abnormal intrauterine pregnancies. AB - Doppler ultrasound (US) evaluation of 40 empty intrauterine sac-like structures was performed to evaluate the ability of this technique to permit distinction between intrauterine pregnancy and pseudogestational sac associated with ectopic pregnancy. Proof of the location of the pregnancy was available in all cases. There were 31 intrauterine pregnancies, of which 23 were missed or incomplete abortions and eight were early normal pregnancies. With an insonating frequency of 3 MHz, the average frequency shift detected from these intrauterine pregnancies was 1.7/1.0 kHz (peak systolic/end diastolic ratio). Nine pseudogestational sacs were evaluated, of which seven demonstrated no flow and two demonstrated minimal flow that averaged 0.4/0.1 kHz. Defining intrauterine peritrophoblastic flow as a peak systolic frequency shift of 0.8 kHz or greater (equivalent to 21 cm/sec with an angle of 0 degree) correctly classifies 26 of the 31 intrauterine pregnancies and all of the nine pseudosacs. The sensitivity of the Doppler technique for the detection of intrauterine pregnancies was 84%, and the specificity was 100%. PMID- 2195592 TI - Patients at high risk for renal artery stenosis: a simple method of renal scintigraphic analysis with Tc-99m DTPA and captopril. AB - Fifty patients with suspected renal artery stenosis (RAS) were studied with renal scintigraphy before and after administration of captopril. Twenty-three patients had RAS (greater than or equal to 75% RAS or greater than or equal to 50% RAS with poststenotic dilatation) and 27 had normal renal arteries at angiography. Angiotensin-converting enzyme inhibitors were discontinued 24 hours prior to renal scintigraphy; all other medications were continued. Each patient was evaluated with a simplified captopril renal scintigraphic protocol: renal imaging after administration of 12 mCi (444 MBq) of technetium-99m diethylenetriaminepentaacetic acid (DTPA), a 3-hour wait, oral administration of 50 mg of captopril, a 1-hour wait, and another scintigram obtained after administration of 12 mCi (444 MBq) of Tc-99m DTPA. Times of peak renal activity (Tmax) were determined from renal time-activity curves, and glomerular filtration rates (GFRs) were calculated with the Gates technique. A Tmax greater than or equal to 11 minutes after injection or a GFR ratio (larger GFR/smaller GFR) greater than 1.5 enabled detection of RAS with 91% sensitivity, 93% specificity, and 92% accuracy. Renal scintigraphy without captopril had only 43%-68% sensitivity in detecting RAS, depending on the criteria used. PMID- 2195593 TI - Gadodiamide injection: nonionic gadolinium chelate for MR imaging of the brain and spine--phase II-III clinical trial. AB - Seventy-three patients with clinically suspected central nervous system abnormalities (44 intracranial, 29 medullospinal) were studied with magnetic resonance (MR) imaging before and after administration of nonionic gadodiamide injection. MR imaging showed intracranial lesions in 37 patients. Eight patients had spinal tumors, and 21 had disk disease. Structural abnormalities were shown in 37 of 44 head studies and in all 29 spine studies. Lesions enhancement was seen in 31 head studies and 28 spine studies, and distinction of lesion(s) from associated edema was possible in 10 head studies and in one study of intrinsic cord tumor. Administration of gadodiamide injection provided improved definition of lesion borders in 19 of 44 head studies and 26 of 29 spine studies. The use of the contrast agent changed the diagnosis that was based on the unenhanced images in nine head studies and 13 spine studies. Early postcontrast, T1-weighted spin echo images of postoperative spines were adequate in distinguishing epidural scar (enhancing) from herniated disk (nonenhancing). The contrast agent was well tolerated, and no drug-related adverse events occurred. PMID- 2195594 TI - Acute appendicitis in children: evaluation with US. AB - During a 4-month period, high-resolution ultrasonography (US) was used to prospectively evaluate 70 children with clinically suspected acute appendicitis. Thirty-five US scans showed a noncompressible appendix with maximal outer diameters greater than 6 mm. This finding was considered positive for the diagnosis of acute appendicitis. Thirty-one of these 35 patients had acute appendicitis documented by surgical and pathologic findings. The remaining four patients were observed, and their symptoms resolved. Thirty-five patients had US scans considered negative for appendicitis. Seventeen of these patients had US findings positive for other conditions including mesenteric adenitis, ileitis, intussusception, Crohn disease, and Burkitt lymphoma. In this series US enabled diagnosis of acute appendicitis with a sensitivity of 94%, a specificity of 89%, and a predictive accuracy of 91%. Diagnosis of acute appendicitis can be made with US with the same accuracy in children as has been previously reported in series of adult patients. The use of US in clinically ambiguous cases may allow earlier diagnosis, prevention of perforation, and decreased complications in the pediatric patient with acute appendicitis. PMID- 2195595 TI - Intravascular US of the distal aorta and iliac vessels: initial feasibility studies. AB - Intravascular ultrasound (US) imaging is a new, evolving technique in which a high-frequency transducer is placed on the tip of a catheter. With this device it is possible to obtain high-resolution images of vessel structure in real time. This may provide valuable information about the degree of stenosis, as well as the type and extent of atherosclerotic plaque, in relation to the underlying tunica media and adventitia. The intravascular US catheter was used in seven patients undergoing transfemoral angiography because of arteriosclerosis obliterans. High-resolution images were obtained in all seven patients, and no complications were noted. Various US findings were demonstrated and correlated with the angiographic findings. PMID- 2195596 TI - Air-contrast barium enema studies after flexible proctosigmoidoscopy: randomized controlled clinical trial. AB - The authors performed a randomized clinical trial to determine the effect of flexible proctosigmoidoscopy (FPS) on the quality of air-contrast barium enema (ACBE) studies performed on the same day and whether it mattered if air or carbon dioxide was used for endoscopic insufflation. One hundred twenty-one patients were randomly assigned to one of the following groups: Same-day studies were performed, with air used for insufflation, in group 1; same-day studies, with carbon dioxide, in group 2; and separate-day studies in group 3. Scout images obtained before the ACBE study were graded for the amount of air seen, and ACBE studies were graded for overall quality; each was graded on a scale of 0-3 in a blinded fashion. The air score was significantly greater in group 1 (2.69) than in group 2 (2.01) (P less than .001), which in turn was significantly greater than in group 3 (1.53) (P less than .01). The ACBE quality scores in the three groups were not significantly different. The authors conclude that FPS can be done before ACBE examination without impairing the quality of the ACBE study. Although carbon dioxide insufflation results in less intestinal air after FPS, the quality of the ACBE study is not affected. PMID- 2195597 TI - Small-field stereotactic external-beam radiation therapy of intracranial lesions: fractionated treatment with a fixed-halo immobilization device. AB - Current techniques of stereotactic, small-field, external-beam irradiation with linear accelerators require treatment with a single fraction or only a few fractions of radiation with large single doses per fraction. Using a radiolucent halo that remained affixed to the cranium with skin-piercing screws, the authors treated 24 patients with a multifraction technique for benign and malignant brain lesions. The objective of this study was to ascertain the feasibility of maintaining the halo in place for a prolonged, multifraction course of treatment, not to assess treatment efficacy. The halo was affixed for multifraction treatments lasting 19-58 days (mean, 38.7 days; median, 40.0 days) and delivered in 16-31 fractions (mean, 24.9 fractions; median, 25.5 fractions). Two of 24 patients experienced superficial skin infection at the site of fixation, but no other significant acute or chronic toxicity attributable to the stereotactic halo was observed. The authors conclude that stereotactic, small-field, precision irradiation can be accomplished with multiple fractions as well as with a single fraction. PMID- 2195598 TI - Intraoperative guidance for intrauterine procedures with transrectal sonography. AB - Transrectal sonography was used for intraoperative guidance in intrauterine tandem placement for intracavitary radiation therapy and in dilation and curettage procedures. The authors describe the method and three representative cases in which it was applied. It is concluded that the technique may prevent complications such as uterine perforation or bladder injury in tandem placement, and that it can facilitate dilation and curettage in complicated cases. PMID- 2195599 TI - Endomyocardial biopsy diagnosis of acute rejection in cardiac allografts. PMID- 2195600 TI - Cardiac transplantation in the pediatric patient. PMID- 2195602 TI - The effects of repeating a recognition test in lorazepam-induced amnesia: evidence for impaired contextual memory as a cause of amnesia. AB - In two experiments, a recognition test for an earlier presented list was given twice in immediate succession (Test 1 and Test 2). On the hypothesis that anterograde amnesia for episodic memory involves a deficit in contextual memory, amnesic subjects should confuse familiarity with distractor items gained during Test 1 with familiarity gained during original list presentation. As a result, they should think that they recognize more items on Test 2. This will lower recognition efficiency in Test 2 by increasing false alarms rather than by reducing hits. For subjects with an amnesia induced by lorazepam, but not for control subjects, recognition efficiency was substantially reduced in Test 2 in both experiments. As predicted, this impairment was due to a large increase in false alarms, with no decrease in the number of hits. The impairment could not be explained by a difference in recognition level between lorazepam and control subjects on Test 1. These findings therefore support the contextual memory deficit hypothesis of anterograde amnesia. Their implications for understanding the relationship between recall and recognition in amnesia are discussed. PMID- 2195601 TI - Social workers' responsibilities in heart transplantation programs. PMID- 2195604 TI - Two-event model for carcinogenesis: biological, mathematical, and statistical considerations. AB - A two-mutation model for carcinogenesis is reviewed. General principles in fitting the model to epidemiologic and experimental data are discussed, and some examples are given. A general solution to the model with time-dependent parameters is developed, and its use is illustrated by application to data from an experiment in which rats exposed to radon developed lung tumors. PMID- 2195603 TI - Pharmacokinetic principles for dose-rate extrapolation of carcinogenic risk from genetically active agents. AB - Neither experimental animal exposures nor real-life human exposures are delivered at a constant level over a full lifetime. Although there are strong theoretical reasons why all pharmacokinetic processes must "go linear" at the limit of low dose rates, fluctuations in dose rate may produce nonlinearities that either increase or decrease actual risks relative to what would be expected for constant lifetime exposure. This paper discusses quantitative theory and specific examples for a number of processes that can be expected to give rise to pharmacokinetic nonlinearities at high dose rates--including transport processes (e.g., renal tubular secretion), activating and detoxifying metabolism, DNA repair, and enhancement of cell replication following gross toxicity in target tissues. At the extreme, full saturation of a detoxification or DNA repair process has the potential to create as much as a dose dependence of risk on dose delivered in a single burst, and if more than one detoxification step becomes fully saturated, this can be compounded. Effects via changes in cell replication rates, which appear likely to be largely responsible for the steep upward turning curve of formaldehyde carcinogenesis in rats, can be even more profound over a relatively narrow range of dosage. General suggestions are made for experimental methods to detect nonlinearities arising from the various sources in premarket screening programs. PMID- 2195605 TI - [GM-CSF: granulocyte and macrophage colony stimulating factor. A biologic agent with a great therapeutic potential in oncology]. PMID- 2195606 TI - [Pregnancy and diabetes mellitus: necessity of greater and continuous multidisciplinary intervention]. PMID- 2195607 TI - [Children and dyslipemia]. PMID- 2195608 TI - [The complex relation of pregnancy and diabetes mellitus]. AB - A glucose metabolism impairment occurs in about 2-3% of all pregnancies. Two different groups of women are involved: diabetic women who become pregnant and healthy women developing gestational diabetes or glucose intolerance during pregnancy. Due to therapeutic improvements and new techniques of fetal monitoring, maternal and perinatal mortality now approaches that of normal pregnancies. On the contrary, congenital anomalies are still four times more frequent. A good control of the mother metabolism is necessary to reduce complications in fetal development, especially during the first six weeks, a crucial period for the early cell division. Fetal monitoring is very important not only to control the normality of the growth and the well-being of the fetus, but also for early identification of possible anomalies. PMID- 2195609 TI - [Medical treatment of diabetic retinopathy]. AB - The pathogenesis of diabetic retinopathy (DR) consists of a complex patch-work of factors correlated and independent on one another at the same time. It is therefore difficult to find pharmaceuticals able to produce different, or even mutually contrasting effects. Another difficulty are the intrinsic characteristics of the disease which after developing to a "critical" stage, evolves with independent mechanism to the most advanced stages. In spite of that, a great deal of medicaments has been suggested so far, all providing therapeutical logic to interfere with one or more pathogenetical stages of the lesions. Although several clinical trials have been performed, survey and follow up are still limited and insufficient to draw conclusion on the effectiveness of medical therapy. In recent times new types of medicaments such as aldose reductase inhibitors and carbonic anhydrase-inhibitors have been suggested. The preliminary results present encouraging perspectives for their use, although caution, until long-term results are available with greater surveys and longer follow-up periods, is advised. PMID- 2195610 TI - Pathophysiology of insulin secretion in diabetes. AB - Knowledge of normal insulin needs and action is of great clinical importance in the case of insulin replacement in Type 1 diabetes, but also for appropriate timing of food intake and initiation of insulin treatment in Type 2 diabetic patients. Thus, hyperglycaemia in diabetes mellitus (DM) may be associated by primary insulin deficiency (DM Type 1) or by impaired insulin action (DM Type 2, early phase) or by both (unsubstituted insulin deficiency in DM Type 1; or DM Type 2 in its late phase). This review investigates to the pattern of insulin secretion in diabetic states and compares the observed phenomena with normal insulin release in healthy man. In particular, it is of note that B-cell function and temporal organization of insulin release is profoundly different and not normal in Type 2 diabetes though overall absolute insulin release (U/24h) may well be within or above the normal range. Such data are to caution the clinician against premature stimulation of endogenous insulin release by sulfonylureas or against too early initiation of insulin treatment in Type 2 diabetes. PMID- 2195612 TI - [Semifasting and type II diabetes mellitus]. AB - The author discusses the very low calorie diet and its physiopathological effects, in the treatment of NIDDM with obesity. In the latter condition the very low calorie diet can be utilized in order to obtain the desired body weight decrease, and consequently to improve glucose tolerance; however, this goal can only be reached by including in the diet sufficient amounts of carbohydrates, and by following some identified parameters of the treated patient. PMID- 2195611 TI - Immunological aspects of diabetes. AB - Notable progress was achieved by the investigations on the immunology of diabetes. Studies of immunogenetics have demonstrated that Type 1 (insulin dependent) diabetes shows a primary association with the HLA class II genes (e.g., with HLA-DR3 and DR4 in Caucasoid populations), a determining features of this type of the disease. Besides, it presents a wide variety of autoantibodies, such as islet-cell cytoplasmic antibodies (ICA), islet-cell surface antibodies (ICSA), complement-fixing islet-cell antibodies (CF-ICA), antibodies to a Mr 64000 islet-cell protein, and many studies are trying to evaluate their pathogenic and predictive role. Various changes of cell-mediated immunity have been also described. The proportion of activated T cells in circulation is increased in patients with Type 1 diabetes. It was assumed that the T cells are the main cause of pancreatic beta-cell damage. Type 1 diabetes is actually considered as a chronic autoimmune disease, with several stages of evolution leading to the destruction of the pancreatic beta-cells, with a consecutive gradual decrease of insulin secretion. From the therapeutic point of view, many problems are raised by insulin immunogenicity, mainly depending on the so-called "contaminants". To avoid phenomena of allergic reactions, immunological insulin resistance, lipodistrophy, a.o., highly purified and human type insulins have been prepared. The insulin autoantibodies (IAA) detected before the clinical onset of Type 1 diabetes are considered a new marker of autoimmunity. New hopeful prospects are opened by diabetes immunotherapy, in which Cyclosporin A detains a particular role, although it should be used only in special conditions, under strict clinical observation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2195613 TI - [Drug pumps]. AB - The aim of therapeutic research is to find out an effective medication against the disease without any dangerous toxic action. The delicate problem is that very often the dose of drug confines with toxicity. The solutions are numerous: transformation of supports, change of the introduction route, adaptation of the concentration. It has been realised that, in certain disease, continuous infusion of medication was much more effective than repeated intermittent injections. The general technic of drug contribution by a pump supposed a drug reservoir with sufficient volume to prevent the frequent manipulations, a source of energy assuring the circulation of the drug and a control of the speed of the drug delivery. These attempts are not exceptional in our practice, being very often utilized in the treatment of difficult diabetes by insulin infusion, the thrombosing diseases be heparin infusion, some forms of diffused cancers by specific chemotherapeutic agents, acute polyhormonal insufficiencies... It is also possible to use infusion pumps in intensive cares with administration of antibiotics, of antalgic drugs, in cardiology for the management of atrial fibrillation, atrial and/or ventricular tachycardias, etc. The most common are the portable pumps and the implantable. PMID- 2195614 TI - Current concepts in pancreas transplantation. AB - Increasing prevalence of insulin-dependent diabetes in associated with a rise in organ complications, markedly increasing morbidity and mortality, especially those of young and middle-aged people. The key role in the etiopathogenesis of diabetic nephropathy, retinopathy and neuropathy is played by a metabolic disorder. The only procedure capable of restoring normal metabolism is replacement of damaged endocrine tissue, i.e., pancreas transplantation. A look back into the history, and a review of current concepts in experimental and clinical pancreases transplantation, highlight some questions to be solved, yet including prevention of the adverse effect of pancreatic hydrolytic enzymes, inhibition of the onset of thrombosis, and timely diagnosis of rejection. The currently employed techniques--pancreatic duct obliteration with polymer, intestinal and urinary bladder drainage of pancreatic secretion--yield approximately similar results. The technique of pancreas transplantation has not been refined to such an extent so as to enable its performance in the early stage of diabetes in a effort to prevent the onset of complications. Patients deriving most benefit from the technique are mainly uremic diabetics undergoing it in combination with renal transplantation which yields optimal results. While a renal graft allows improved detection of pancreas rejection, a pancreatic graft confers protection against recurrence of diabetic nephropathy. Simultaneous transplantation of both organs represents not only a life-saving procedure, it also offers appreciable improvement of the quality of life of the diabetic patient. PMID- 2195615 TI - [Current approach in the prevention and treatment of diabetic nephropathy]. AB - Diabetic renal microangiopathy accounts for enormous morbidity and mortality, particularly in patients who develop diabetes in childhood or early youth; in the last few years its pathogenesis has been therefore extensively studied, aiming to prevent renal complications or at least of slowing down its progression toward uremia. Though not always in accordance with theoretical expectations, the results of clinical trials have nevertheless widened our therapeutic possibilities; in fact, besides the attainment of an optimal metabolic control, other possible interventions include a careful correction of albeit minimal elevations in arterial pressure; the interference with intrarenal hemodynamic parameters; the correction of insulin-independent metabolic pathways, abnormally activated in the diabetic, such as non enzymatic glycation and polyol pathway; the treatment of endothelial and platelet alterations; the improvement of the rheologic properties of blood. PMID- 2195617 TI - [Surgery of the endocrine glands: myth or reality?. Status of 2 years of activity]. PMID- 2195616 TI - Anti-tumor effect of cisplatin, carboplatin, mitoxantrone, and doxorubicin on peritoneal tumor growth after intraperitoneal and intravenous chemotherapy: a comparative study. AB - Tumor growth was studied in a peritoneal tumor model in the rat after intravenous and intraperitoneal administration of doxorubicin (4 mg/kg), mitoxantrone (2.5 mg/kg) and cisplatin (4 mg/kg) and after intraperitoneal administration of carboplatin (20 mg/kg). All treatments delayed tumor growth and intraperitoneal treatment was more effective initially than intravenous treatment for all drugs tested. Regrowth occurred between 2 and 7 weeks after treatment and was less pronounced after intravenous treatment. Tumor sizes in cisplatin treated rats 7 weeks after treatment were comparable after intraperitoneal and intravenous treatments. Intraperitoneal carboplatin even with a dose 5 times higher than cisplatin resulted in a less tumor growth delay in all stages of the treatment, compared to cisplatin. All cytostatic drugs, except carboplatin, induced loss of body weight. Weight loss was similar for intraperitoneal and intravenous treatment with both cisplatin and mitoxantrone while for doxorubicin the weight loss was significantly higher after intravenous treatment than after intraperitoneal therapy. Considering the "therapeutic index", defined as the ratio of tumor growth delay to weight loss, cisplatin had the highest "therapeutic index", 1.5 (intraperitoneal) and 1.7 (intravenous) compared to 0.3 (intraperitoneal) and 0.6 (intravenous) for Mitoxantrone and 0.4 (intraperitoneal) and 0.5 (intravenous) for doxorubicin. This indicated that cisplatin was the most favorable drug to use in this peritoneal tumor model for both intraperitoneal and intravenous treatment. The tumor growth delay was initially more pronounced after intraperitoneal cisplatin compared with intravenous. PMID- 2195618 TI - [The Sneddon syndrome--diagnostic, etiological and therapeutic aspects]. AB - Sneddon's syndrome represents a neurocutaneous disorder that, as a nosological entity, has first been described in 1965. This syndrome is characterized by the association between generalized racemose livedo and disorders of the central nervous system, predominantly being present as cerebrovascular lesions and seizures. So far, Sneddon's syndrome has received little attention, though a considerable part of patients with cerebrovascular events are suffering from this disease. The usual onset of clinical manifestations is in the third to fourth decade. Vascular risk factors are commonly found. For introduction of Sneddon's syndrome to a wider audience a case is reported, the clinical features, aspects of diagnosis and differential diagnosis, pathogenesis, prognosis, and treatment are discussed. PMID- 2195619 TI - [The history of epileptology and electroencephalography with special reference to the Swiss and Polish contributions]. PMID- 2195620 TI - [Psychomotor epilepsy: phenomenology, localization, pathogenesis and therapy]. AB - Next to tonic-clonic seizures psychomotor (complex focal) seizures are the most common form of all epileptic seizures, except in infancy where they are seen rarely. Differently from generalised non convulsive seizures (like petit mal absences), their first appearance has no typical age limit, however, their proportion to other forms of seizures increases in adolescence and adults especially between the third and fifth decade of life. The main symptom is the disorder of consciousness which lasts at least more than half a minute, normally several minutes in completely distinct seizures, which doesn't begin abruptly and which often ends ill defined. This twilight attack is proceeded by an aura of sensory, psychic or vegetative character. The aura is followed either by a transitory state of immobility and later by motor phenomena or at once by motor phenomena in the form of diverse automatisms of variable intensity, reaching from mild movements in the oral region over verbal expressions to highly dramatic scenes, often accompanied by vegetative symptoms. Tonic versive and tonic symmetrical or tonic asymmetrical seizure symptoms are quite often motor variants which also can lead to sudden drops. Psychomotor attacks can be reduced to "pseudo-absences", however, they also can develop into tonic-clonic seizures (Grand mal). Generally, the succession of seizure symptoms is constant in the same patient, the expression can differ from seizure to seizure. Psychomotor attacks can be spread over the whole day or can show a strict connection to sleep, in the course they can likely occur in clusters and can accumulate to a continuous or discontinuous form of psychomotor status epilepticus. Predominantly, but not exclusively psychomotor attacks start from the temporal lobe, whereas neocortical temporal attacks (especially of lateral posterior origin) can be distinguished from those coming from the limbic system, especially from hippocampal or mesio-basal temporal structures and from the nucleus amygdalae. About 20% of the psychomotor attacks are of frontal origin coming from the mesial frontal region or from the gyrus cinguli anterior. Also seizures of occipital or parietal origin can spread so quickly that the seizure itself is impressing as a "temporal lobe attack". On account of that, epilepsies with psychomotor attacks cannot be compared to temporal lobe epilepsies. The etiology of psychomotor epilepsies is closely connected to the topographic site of the temporal lobe, who is especially vulnerable for traumatic lesions, cerebral edema and hypoxemia. Also small dysgeneses, heterotopies or small abnormalities of vessels are relatively often found in surgical specimens.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2195621 TI - [Humidifier syndrome as occupational disease in Switzerland]. AB - Control of humidity may be necessary in various industrial processes. Contamination of humidifiers by algae and bacteria may lead in exposed workers to two distinct syndromes: extrinsic allergic alveolitis and humidifier fever. In Switzerland 18 cases of humidifier syndrome were accepted by SUVA as occupational disease. 13 of the 18 cases occurred in the printing industry. In 13 out of 18 cases contaminated humidifiers were the cause of the syndrome and in five cases contaminated air-conditioning systems. Due to the often uncharacteristic clinical signs and symptoms and variable clinical features diagnosis of humidifier syndrome was missed by the general practitioner. Once humidifier fever was clearly diagnosed most workers had to change their working place. Despite the avoidance of exposure respiratory problems, radiographic changes and pulmonary function changes often persisted. Major pulmonary function decreases resulting in pulmonary invalidity were observed in five of the 18 cases (28%). Technical measures to prevent humidifier syndrome are described. PMID- 2195622 TI - [Bleeding and pain following anal surgery]. AB - Bleeding and pain are frequent complications, following proctological procedures. Their intensity however, can be influenced by the therapist. Through careful hemostasis and wound closure the risk of bleeding is greatly reduced so that most procedures can be done on an outpatient basis. The intensity of pain experienced by the patient is very much personality dependent and is in general unpredictable. Pain can be reduced by using an improved technique (high position of rubber-band ligation, manual anal dilation). This paper deals mainly with bleeding and pain following treatment of external hemorrhoids, inner piles, fissure-in-ano, abscesses and fistulae. PMID- 2195623 TI - [Paucity of intrahepatic biliary ducts in adults]. PMID- 2195624 TI - [Verapamil and hypertension--(multicenter study of the efficacy and tolerance of delayed-action verapamil in the treatment of essential hypertension)]. PMID- 2195625 TI - [HELLP syndrome. Apropos of a series of 9 cases without disseminated intravascular coagulation]. AB - The Hellp syndrome defined as the association of micro-angiopathic haemolytic anemia, hepatic cytolysis and thrombocytopenia, correspond to a severe form of gravidic toxemia, combined to manifestations of classic-pre-eclampsia. This retrospective study, conducted over 6 years, concerns 9 cases of Hellp syndrome, including 2 occurring during the immediate post-partum. Only cases where this biological triad was obvious and not associated with manifestations of disseminated intravascular coagulation, were considered in this study. In addition to the usual criteria of gravidic toxemia, the early clinical manifestation occur, in this study, between 28 and 38 weeks of amenorrhea and gastrointestinal manifestations are predominant. The physiopathogenic hypotheses of this syndrome remain variable and management varies depending on the authors. Treatment is that of pre-eclampsia. Medical treatments (steroids, heparin, immunosuppressants,...) are discussed, but severe feto-maternal complications require, most of the time, a surgical approach, depending on the number of pregnancies, the obstetrical conditions, the stage of the pregnancy and the severity of the syndrome. PMID- 2195626 TI - [Antiprogesterone, prostaglandin analogues and the early interruption of pregnancy]. AB - Early termination of pregnancy, or menstrual regulation, is recommended for use within 7 weeks of amenorrhea, ie 49 days. Aspiration is a widely used method, with a failure rate of 2 to 5 p. cent and a complication rate of 4 p. cent. But, aspiration need experienced practitioners. Prostaglandins may be used with efficacy. New analogues (sulprostone, meteneprost, gemeprost) are studied. The success rate is over 90 p. cent, but severe uterine pains occurred in 50 p. cent of cases, as gastro-intestinal side effects. Mifepristone is an antiprogesterone steroid which is able to terminate early pregnancy with a success rate of 80 p. cent and very few side effects. The combination of mifepristone and a low dose of a prostaglandin-analogue is a very well tolerated procedure with a success rate of 95 p. cent. It seems to be a good alternative to early aspiration. PMID- 2195627 TI - [Significance of blood uric acid determination. Review of the literature]. AB - Determination of the blood uric acid levels is still a weak indicator in the evaluation of the prognosis of fetal distress when compared with materno and feto placental vascular tests. Its diagnostic and prognostic value in case of maternal gravidic nephropathy could be improved by a specific uricase titration and initial determination at the beginning of the 2nd trimester. Elevated uric acid levels would therefore be undeniably helpful in selecting the form of treatment. PMID- 2195628 TI - [Resistance to contraception]. AB - While contraception has been an acquired freedom for more than 10 years, a number of women present clinical manifestations resulting in the restriction or the suppression of this freedom. The symptoms are extremely diversified, from forgetting the pill to severe depression, from repeated infections to personality disorders. If many symptoms may be explained from an organic standpoint, others only derive from an unconscious resistance to contraception. The authors attempt to determine the origins of such resistance, their possible variations and advocate a management protocol for patients presenting this type of disorder. PMID- 2195630 TI - Prosthodontic management of head and neck cancer patients. II. PMID- 2195629 TI - [Echographic screening: small, yes... but why?]. AB - This study concerns a case of micromelus dwarfism discovered after 30 weeks of amenorrhea, during a second systematic sonography performed in a second pregnancy without pathological history and a normal first pregnancy. This dwarfism is complete, without any associated malformations, but on the contrary a moderate hypotrophy. In addition, the morphology of the long bones is normal, without any evidence of fracture; hand and feet are in normal position, with five digits. Radiography of the uterine contents confirms these findings and shows a normal bony transparency. The karyotype is female, without any anomaly. Spontaneous delivery occurs normally at 39 weeks of amenorrhea. The little baby girl presents, at birth, a slight facial dysmorphism, low height and weight, without any other obvious malformation. The radiological and sonographic evaluation performed in the pre and postnatal periods does not permit a definite diagnosis. The diagnosis of achondroplasia or hypochondroplasia is temporarily made. At the age of 6 months, Laurie consults Professor Maroteaux, specialist in children bone diseases, who feels that this is more likely a congenital spondyloepiphyseal dysplasia. These extremely rare and unclear diseases make a precise prenatal diagnosis particularly difficult. A tentative classification according to the bony transparency and certain sonographic aspects, is presented at the end of this study, knowing that a diagnosis and therefore a prognosis should be considered with the utmost caution. PMID- 2195631 TI - [Immunologic mechanisms of intrauterine sensitivity. A review article]. PMID- 2195632 TI - Screening for neurotoxicity: complementarity of functional and morphologic techniques. AB - Our philosophy is that screening tests should be applicable across species and emphasize complementarity to neuropathology. Within this context, electrophysiological tests comparable to those in human clinical neurology are powerful screening tools. For example, while histopathologic evaluation of the cochlea for ototoxicity is difficult, evoked potential audiometry is fast and easy. In this instance, one might routinely screen for deficits in auditory function, and reserve morphologic techniques for a characterization role rather than one of discovery. Lesions of neurons, axons and myelin are, however, readily assessed by light microscopy. A suitable combination of functional and morphologic screening tests, therefore, enhances the ability to discover neurotoxicity, and these data often are ideal for generation of refined hypotheses for subsequent characterization studies. PMID- 2195633 TI - Neuronal disorders: studies of animal models and human diseases. AB - The peripheral nervous system and the central nervous system (CNS) are comprised of assemblies of neurons that communicate via electrical and chemical signals. Different disease processes selectively affect specific populations of neurons and/or specific cell functions (i.e., "selective vulnerability" of neurons is a principal determinant of phenotypes of disease). New cellular and molecular biological approaches have begun to clarify some of the mechanisms of selective cell injury in human diseases and their animal models. Following a brief review of the normal biology of nerve cells, we use illustrations drawn from studies of experimental and human diseases to discuss the mechanisms of structural/chemical abnormalities that occur in a variety of neuronal disorders. PMID- 2195635 TI - Artifacts in routinely immersion fixed nervous tissue. AB - In order to demonstrate the types of artifacts commonly seen in inadequately fixed central nervous system (CNS) tissues, rat brains were fixed by either perfusion or immersion in 10% neutral buffered formalin. Perfused brains were either removed immediately or left in situ for 1 hr prior to removal. Some of the brains destined for immersion fixation were first allowed to sit for either one half or 1 hr in either room air or in an isotonic saline solution. Other brains were subjected to various handling procedures immediately after removal from the cranial vault in order to simulate the types of trauma which commonly occur during routine removal/dissection. Commonly observed artifacts included the presence of basophilic (dark) neurons, retraction spaces around neurons, vessels, and glial cells, displacement of the neuropil, and neuropil vacuolar change. The results of the fixation and handling procedures utilized in the collection of these brains substantiate the well documented fact that the least degree of artifact will be seen in brains fixed by perfusion and left in situ for a reasonable period of time (several hours) prior to removal. PMID- 2195634 TI - Quantitative assessment of inner ear pathology following ototoxic drugs or acoustic trauma. AB - Techniques currently used in the assessment of structural and/or functional damage to the peripheral auditory system are summarized. Two histological approaches are described: one which allows light microscopic evaluation of all structures of the auditory periphery, and a second which concentrates on the sensory cells and their innervation. The latter technique allows electron microscopic analysis of selected regions after a thorough light microscopic survey. Two electrophysiological methods are described as well: a single-fiber approach which provides detailed information about cochlear condition at all frequency locations and a simpler and faster evoked-potential approach which is well suited to screening for cochlear changes. The correlations between structural and functional changes are described using examples from studies of acoustic injury of the inner ear. PMID- 2195636 TI - Neuropathology of excitatory neurotoxins: the domoic acid model. AB - A novel type of intoxication in Canada in 1987 was traced to consumption of cultivated mussels contaminated with the excitotoxin domoic acid. Studies carried out in rats and monkeys revealed that parenterally administered domoic acid induces in rats neuroexcitatory phenomena culminating in seizures. Monkeys respond with gagging, emesis and less clearly evident seizure activity. CNS damage consisting of dendrotoxic and gliotoxic edema and nerve cell degeneration occurs in structures of the limbic system and the retina in both species. CNS lesion distribution similarities in animals treated with domoic acid or kainic acid suggest that these excitotoxins share a common pathogenesis mediated by glutamic acid, a putative endogenous excitatory neurotransmitter. PMID- 2195637 TI - Role of the blood-nerve barrier in experimental nerve edema. AB - Nerve edema is a common response to the nerve injury seen in many peripheral neuropathies and is an important component of Wallerian degeneration. However, independent pathologic effects of nerve edema that aggravate or induce nerve injury extend the role of edema beyond that of an epiphenomenon of injury. New insights into the mechanism and impact of nerve edema come largely from animal models. In the following review, we discuss the cause and consequences of nerve edema with particular reference to endoneurial fluid pressure and its relevance to the nerve microenvironment. Experimental models of nerve edema include conditions with increased vascular permeability such as lead poisoning, experimental allergic neuritis, and murine globoid leukodystrophy. Increased perineurial permeability induced by local anesthetics and neurolytic drugs can also induce nerve edema sufficient to increase endoneurial fluid pressure. Both perineurial and vascular permeability are increased after damage induced by crush, freeze, or laser injury. One of the most important forms of nerve edema is induced by external compression; the significance of this change is that edema has local compressive effects that persist after the external pressure has been relaxed. Nerve edema and increased endoneurial fluid pressure also occur in conditions in which vascular permeability appears to be unchanged such as experimental diabetic neuropathy and in hexachlorophene intoxication. In both of these conditions, reduced nerve blood flow has been demonstrated in rats and is viewed as a consequence of increased endoneurial fluid pressure. Whatever its mechanism, endoneurial edema has important structural and functional consequences for nerve fibers. A clear understanding of the underlying pathology of the nerve microenvironment may provide useful insights into treatment of clinical neuropathies. PMID- 2195638 TI - Characterization of N-nitrosourea-induced tumors of the nervous system; their prospective value for studies of neurocarcinogenesis and brain tumor therapy. AB - Two decades of research with resorptive neurocarcinogens firmly established the high potency of methyl and ethylnitrosourea (MNU and ENU) as neurocarcinogens, particularly in rats. There are significant differences in susceptibility to these agents among species. There are also differences among age groups. Fetuses are between 50 to 100 times more susceptible than adult rats. One single iv inoculation of 20-50 mg/kg ENU into pregnant rats may produce neurogenic tumors in 100% of the offspring. The tumors produced by these compounds have been well characterized morphologically, biologically, biochemically and histochemically. Tumors produced by both compounds are mostly gliomas and neurinomas (Schwannomas), however, clear differences exist between ENU and MNU produced neoplasms. Transplacental exposure to ENU generally results in a high number of anaplastic neurinomas and mostly differentiated gliomas (astrocytomas, oligodendrogliomas or mixed gliomas). In contrast, multiple exposures of adult rats to MNU result in a moderate number of mostly differentiated neurinomas and a high number of anaplastic gliomas. Tumors usually start out as well differentiated oligodendrogliomas or astrocytomas. As they grow larger, they become more mixed and anaplastic. In contrast to spontaneous gliomas in old rats, MNU and ENU-induced astrocytomas can be readily identified with well established biomarkers such as the S100 protein and particularly GFAP (glial fibrillary acidic protein). Neurinomas are also strongly positive for S100 protein. No reliable markers exist for oligodendrogliomas. Neurogenic tumors induced by MNU or ENU, as well as derived cell lines and clones from such tumors, have been successfully used as models for neurocarcinogenesis and therapeutic screening.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2195639 TI - Cellular and molecular aspects of neurocarcinogenesis. AB - Although the morphology of neural tumors induced in rats by N-ethyl-N-nitrosourea (NEU) and related alkylating agents has been extensively investigated, their histogenesis and the molecular basis of malignant transformation are still largely unknown. This review gives an account of the interaction of neurocarcinogenic agents with cellular DNA, the possible role of promutagenic O6 alkyldeoxyguanine and their deficient repair by the cerebral O6-alkylguanine-DNA alkyltransferase. A new experimental model is described in which neural tumors are induced in fetal brain transplants. Pregnant rats received a single iv dose of NEU (50 mg/kg) on the 14th day of gestation. One day later, suspensions were prepared from the fetal forebrain and stereotactically injected into the caudoputamen of adult rats. After additional exposure to NEU of the host animals 8 days and 9 weeks post transplantation, all rats developed brain tumors within the neural graft. Histopathologically, all neoplasms were classified as olidogdendrogliomas. Other neoplasms typically induced by NEU transplacentally (astrocytomas, mixed gliomas, ependymomas) were absent. The selective induction of oligodendrogliomas indicates that neoplastic transformation in the nervous system can occur in a differentiated glial cell or a precursor cell committed to oligodendrocytic differentiation, and that transformation of a pluripotential stem cell is not necessary. Transplacental exposure of the donor fetuses to NEU alone, i.e., without additional postgrafting exposure, did not produce brain tumors in any of the experimental animals indicating that in the microenvironment of fetal brain transplants the multistep development of gliomas requires additional mutational events. Malignant schwanomas perinatally induced by NEU carry a point mutation in the transmembrane domain of the neu gene. The mode of oncogene activation in NEU-induced CNS gliomas has not yet been elucidated. We have used cerebral grafting techniques to study the effects of known oncogenes on the developing nervous system, taking advantage of efficient gene transfer by replication-defective retroviral vectors and of the extraordinary capacity of fetal CNS to differentiate in and fully integrate with the host brain. Rats carrying transplants exposed in vitro to the polyoma medium T-antigen developed endothelial hemangiomas in the graft which often led to fatal cerebral hemorrhage within 13-50 days after transplantation. Introduction of the viral src gene caused astrocytic and mesenchymal tumors after latency periods of 2-6 months. Following infection of fetal donor cells with a vector encoding the v-myc oncogene, only a single embryonal CNS tumor was observed whereas exposure to v-H ras produced a low incidence of gliomas.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2195640 TI - New approaches to neuroretinal evaluation. PMID- 2195641 TI - The use of laboratory animals in toxicology: an ophthalmoscopic assessment. AB - In a recent text by Grant (3), approximately 2,800 substances are listed as having some type of untoward effect on ocular tissue. The kinds of substances that may cause toxic damage/effects range from carbolic acid (2) to oxygen (1). It is the purpose of this communication to briefly review ocular toxicology as investigated in laboratory animals. PMID- 2195642 TI - Developmental neurotoxicology. AB - Some injuries to the developing nervous system can be detected with traditional evaluation for morphologic pathology, but many early injuries differ in character from those that are produced later in life. Such injuries arise from interference with developmental processes, rather than destruction of tissue. For example, an injury which kills neurons in the mature CNS leads to gliosis and a reduction in neuronal density, but a reduction in the number of neurons produced during development is not likely to lead to gliosis, and typically affects tissue volume rather than cell density. Some effects of developmental insults, such as misplaced and misoriented neurons, are never seen after adult injury. Functional effects reflect the role of the CNS in physiological regulation as well as in behavior. To evaluate CNS for developmental injury, it is necessary to know something about the structural and functional outcomes already recognized to result from teratogens and how these effects are related to time of exposure and time of testing. PMID- 2195643 TI - Behavioral indices of neurotoxicity. AB - There are many classes of chemicals widely used in a number of commercial and industrial processes having a potential to affect adversely the nervous system. Because of their relative sensitivity to some agents and general noninvasive characteristics, functional measurements of neurotoxicity are being used with greater frequency, especially at the level of hazard identification. The neurobehavioral test battery used by the National Toxicology Program (NTP) includes motor activity, fore- and hindlimb grip strength, acoustic startle response, responsiveness to an adverse thermal stimulus and general health and clinical measures (body weight, autonomic signs, tremor, convulsions). These tests have been used in nearly 40 studies involving various dosing regimens with rats and mice. The NTP battery shows several salient features of an effective screen, including the ability to differentiate known neurotoxicants from nonneurotoxicants, identify certain types of neurological sequelae or profiles of neurotoxic effects and construct dose- and time-response data in a screening context. The extent to which the NTP battery has predictive validity is still being evaluated. PMID- 2195644 TI - [Intra-arterial chemotherapy in oral cancers. A current therapy?]. AB - Reviewing arguments based on the pharmacokinetics of arterial infusions, on literature study results, and on their personal experience with 16 patients, the authors present a case for the administration of antitumoral agents by intra arterial infusion as a method of dispensing induction chemotherapy to stomatological cancer patients. Utilization of implanted sites and discriminating selection of indications will improve the performance of intra-arterial chemotherapy. PMID- 2195645 TI - [Glossodynia]. AB - Glossodynias are a build up of painful lingual syndromes with neither a detectable visible lesion, nor of a known organic origin. An obvious discordance between the subjective feelings and the weakness, even absence of an objective lesion support able to explain them, can be observed. Being often considered by physicians to be of a psychological origin, they are always the object of never ending research for a detectable lesion which would explain their complications. Following consultations with 114 patients in the department of Stomatology, and in collaboration with our neuropsychiatrist colleagues in the same hospital, we took stock of this frequent application which bothers the buccal specialist, who does not know to consider it or how to treat it. PMID- 2195646 TI - [Cysts and pseudocysts of the parotid]. AB - Parotid gland are subdivided in malformative dysgenetic cysts and in acquired cysts. Among malformative cysts, lymphoepithelial cysts so-called branchial cysts are the most frequent. Histologically the cystic cavity is lined by squamous epithelium with various amounts of underlying lymphoid tissue. Other varieties of malformative cysts are exceptional: cystic teratomas with several sorts of adult tissues, polycystic parotid gland and congenital ductal ectasia. Acquired cysts are another important group: retention cysts are found in adult and old people. Microscopically these cysts are lined by a single or pseudostratified epithelium rested on a layer of connective tissue without any lymphoid tissue. Lymphoid cystic hyperplasia arising in HIV infection can be included in this group of acquired cysts. Finally these parotid cysts have to be differentiated from pseudocysts without an epithelial lining and from cystic tumors as cystadenolymphoma and cystic mucoepidermoid carcinoma. PMID- 2195647 TI - [Cysts and fistulas of the lateral neck. Apropos of 18 cases with a review of the literature]. AB - Lateral cysts and fistulas of the neck are branchial cleft malformations. Lateral fistulas occurring at the basis of the neck account for about 5% of all congenital neck fistulas. Concerning 18 personal case observations of 2nd and 3rd branchial arch cysts, the authors report the chief clinical findings in this type of malformation, as well as discussing fistulography as a valuable investigational technique. They present the characteristics of surgical therapy as the sole possible solution. PMID- 2195648 TI - [Le Fort osteotomy. A study of the complications from a review of the literature and from a homogenous series of 50 patients]. AB - Since Wassmund in 1927, the Le Fort I osteotomy became a popular procedure in maxillo-facial surgery. Review of the literature is presented with a series of 50 homogenous patients. The authors show that they are few complications of this operation although theoretically may look numerous. The intra and post-operative haemorrhages are infrequent and never alter the vital prognosis. The bony necrosis disappeared since the last technical improvements. The secondary displacement remains a problem which seems less important actually because of the use of plates and screws, and the improved surgeon's skill. So, the Le Fort I osteotomy become a reliable surgery since indications and technical points are respected. PMID- 2195649 TI - Is the effect of alternative medical treatment only a placebo effect? AB - A common assertion about alternative medical technologies is that their results are solely built upon the placebo effect. The reason for this assertion is due to the facts that the placebo effect is perceived as an irrational quantity, and that the placebo effect is considered unspecific. If it is possible to rehabilitate the placebo effect by interpreting it as a specific effect, what consequences would it have for school medicine and the view of certain alternative medical technologies? To answer these questions it is necessary to investigate just what sort of phenomenon the placebo effect is, and what determines its dimensions. PMID- 2195650 TI - An evaluation of the effectiveness of tobacco-control legislative policies in European Community countries. AB - The purpose of this paper was to assess the effectiveness of anti-tobacco smoking legislation from 1948 onwards in reducing actual per capita tobacco consumption in the twelve countries of the European Economic Community (EEC). In order to undertake these assessments a score was assigned to every legislative measure, indicating the a priori likely impact of this measure on tobacco consumption. Two approaches were then utilized. In the first, it was found that the cumulative anti-tobacco legislative score correlates well in time with a reduction of tobacco consumption. In the second, cross-sectional data from the EEC countries and multiple regression modelling were used to estimate the elasticities of tobacco price, per capita income and cumulative anti-tobacco legislation score; it was found that legislation has an impact on tobacco consumption which, although considerably smaller than the corresponding impact of tobacco price levels, is nominally significant and potentially important. The evaluative approaches utilized in this paper are based on observational data of ecologic nature and can provide only weak evidence about the causal nature of the reported associations. Nevertheless, this limited evidence suggests that legislative measures may be effective both by affecting price levels and through other mechanisms, including health education and the formation of a more general anti smoking ethos. PMID- 2195651 TI - Multielement analysis of biological materials by particle-induced X-ray emission (PIXE). AB - An analytical particle-induced X-ray emission (PIXE) procedure for the multielement analysis of biological materials consists of various stages. These include sample and specimen preparation, specimen bombardment, spectral data processing, quantification and correction for matrix effects. Critical aspects of the procedure are contamination and/or losses during sample and specimen preparation and the danger of radiation or heat-induced losses during specimen bombardment. With optimized PIXE procedures precisions of 1-2% and an accuracy of better than 5% are obtainable, whereas the detection limits are down to 0.1 microgram/g. Because of its inherent characteristics, PIXE offers great potential for trace element analysis in the biological and medical fields, and this is demonstrated through selected examples of applications. PMID- 2195652 TI - Evidence that a major portion of cellular potassium is "bound". AB - In this report we briefly review recent evidence which shows that a substantial proportion of intracellular K+ is "bound" or perturbed from the physicochemical properties expected in dilute aqueous solutions. In addition, we present evidence from electron probe x-ray microanalysis of thin cryosections of cells which indicates that the binding of K+ to anionic groups either carboxyl groups (HCO2) on proteins or to phosphate groups in creatine phosphate (CrP), in adenosine triphosphate, (ATP), in protein and in nucleic acids, are the main determinants of the maintenance of (as differentiated from the generated of) the well known intra- to extracellular K+ concentration difference. The collective evidence suggests that much of cellular K+ is reduced in its mobility and in its chemical activity due to association with negative charge groups (e.g. carboxyl and phosphates). This fact forces abandonment of the misleading assumption that the majority of intracellular K+ and other inorganic ions are as free as would be expected under ideal solution conditions. This realization should have far reaching consequences toward understanding transmembrane movement of water and solutes in cells. PMID- 2195653 TI - [Transesophageal echocardiography]. AB - Transesophageal echocardiography is a new, semi-invasive technique for the examination of the heart and the aorta. Within 10-15 minutes it is possible to obtain good pictures of the anatomy and function of the heart. Diagnostic indications are native and prosthetic valvular heart disease; the method is particularly suitable for visualization of endocarditic vegetations, evaluation of embolic events or congenital heart disease and assessment of aortic dissection. In the intensive care unit transesophageal echocardiography is a new window to the heart, yielding instantaneous information on cardiac status. For the anesthetist it is the first method to provide perioperative beat to beat analysis of ventricular function. PMID- 2195654 TI - [The problem of the effectiveness of condoms against HIV infection]. AB - In several countries the condom is recommended as the most important protection against HIV infection, although there is no proof that the condom is effective against sexually transmitted diseases (STD). Prior to the HIV epidemic the condom was used to prevent pregnancy and to decrease the risk of STD. To prevent a deadly infection such as that with HIV, safe ways of protection are mandatory. Recent studies on HIV prevention show the assumption that condoms provide reliable protection against HIV to be a dangerous illusion. In carefully planned studies the residual risk was 13% and 27% and more respectively. PMID- 2195655 TI - Site-specific cleavage of a yeast chromosome by oligonucleotide-directed triple helix formation. AB - Oligonucleotides equipped with EDTA-Fe can bind specifically to duplex DNA by triple-helix formation and produce double-strand cleavage at binding sites greater than 12 base pairs in size. To demonstrate that oligonucleotide-directed triple-helix formation is a viable chemical approach for the site-specific cleavage of large genomic DNA, an oligonucleotide with EDTA-Fe at the 5' and 3' ends was targeted to a 20-base pair sequence in the 340-kilobase pair chromosome III of Saccharomyces cerevisiae. Double-strand cleavage products of the correct size and location were observed, indicating that the oligonucleotide bound and cleaved the target site among almost 14 megabase pairs of DNA. Because oligonucleotide-directed triple-helix formation has the potential to be a general solution for DNA recognition, this result has implications for physical mapping of chromosomes. PMID- 2195656 TI - Nuclear medicine information management systems. AB - There are good arguments for considering a computer system to improve timeliness and quality of patient care, enhance the format of clinical reports, and strengthen management controls for the containment of health care costs. A nuclear medicine information management system serves to fill these needs. Receptionists access the system to schedule patient studies, log patient data, and generate examination records. Secretaries transcribe and print clinical reports. Film library staff locate patient films and keep track of borrowed studies. Technologists produce study work sheets, record quality assurance information, and process the examination results. Staff preparing radiopharmaceuticals use the system to receive and inventory tracer stocks, track preparation and dispensing activities, and to keep records for external review. Clinicians use it to look up old study results and record their study impressions. Managers access statistical reports, billing information, and resource utilization data. This review describes an information management system as implemented in a nuclear medicine clinic. Software applications for patient scheduling, radiopharmacy, film management, report generation, quality assurance, and inventory control are described as implemented on a variety of academic and commercial systems. Hardware architectures and the issues surrounding system specification and installation are explored. PMID- 2195657 TI - Research on AIDS interventions in developing countries: state of the art. AB - This paper reviews achievements of past and current research on AIDS interventions in developing countries, and identifies three major issues. (1) Several areas of research have been severely neglected, namely transmission from mother to infant, the impact of treating curable STD and transmission in health care settings. (2) AIDS intervention research is mainly concerned with behavioral changes in a very intimate part of human lives, namely sexual relationships. This makes it difficult to design studies that are at the same time ethically acceptable and scientifically sound. A more creative mix of methodologies is needed, that goes hand in hand with a close collaboration between researchers from the social sciences and health sciences field. (3) Counseling is a major aspect of any targeted AIDS intervention program. However, there is no evidence yet for the effectiveness of specific messages and particular forms of counseling. Investigation in this area is urgently needed. PMID- 2195658 TI - Social work in medical and health settings. Introduction. PMID- 2195659 TI - Social work practice theory: a trans-cultural resource for health care. AB - This paper examines the development of the theoretical base of social work practice as it has moved from a value base of care and concern to an identification with scientifically based theory. Rather than moving to a unified body of theory the profession is at a point where there is a range of theoretical bases which differentially impact on the profession in different regions of the world. It is argued that in the health care system it is necessary to develop a richly diverse structure of service delivery patterns to respond sensitively to the variations in cultural patterns and that the current diversity in social work theory serves as a useful model for such a goal. An increased comfort with theoretical plurality can serve as a resource in the expansion of a world-wide system of responsive health services. PMID- 2195660 TI - Social work in health care: directions in practice. AB - As technological advances within biomedicine uncover more complex and confusing situations, social workers are forced to deal with the patient and family with greater uncertainty. To competently address today's biomedical environment with an anticipation of tomorrow's advances is an incredible challenge. The focus of the theoretical framework necessary as the foundation for health care practice has shifted from an emphasis on psychopathology to a focus on what people do well, on their adaptive capacities with the goal of preventing maladaptive behavior. Therefore, the focus of practice must be on factors that affect normal or typical growth and development in the course of living and must include an understanding of the interaction between the biological, psychological, cognitive, social, cultural, and environmental dimensions of social functioning. PMID- 2195661 TI - Person/environment construct: positivist versus naturalist, dilemma or opportunity for health social work research and practice? AB - The purpose of this paper is to indicate that there is nothing fundamentally wrong with the social work purpose of simultaneous attention to persons in their contexts. In fact, the productive pull of both perspectives is what separates social work from other helping professions. Indeed, it is what separates health social work from other health professions. What has created difficulty, however, has been the predominant lens through which person and environment have been investigated, understood and manipulated. This paper compares two major models of knowledge building in an attempt to identify the consequences for research and practice in social work. Examples are provided from both research and practice that derive from these differing perspectives in an effort to clarify the choices social worker health professionals make when encountering a person-in situation. PMID- 2195662 TI - Between social and somatic disorders: the promotion of health as part of general social work practice. AB - The population of the highly industrialized countries have access to an increasing range of possibilities for influencing their own state of health in both positive and negative ways. Health maintenance behavior is part of a general 'way of life' which is determined by chosen life styles. While the clients of professional social work may have a more restricted range of options, the interdependence of their individual life situations and health disposition remains a factor in their case as well, usually with negative results. There is a constant mediation of social disorders in somatic disorders (and vice versa, especially in cases of chronic illness, disability and addiction). This paper discusses aspects of assessment, coping styles and social support along the socio psycho-somatic axis. There are many arguments for a conscious integration of health promotion into social work practice in general. PMID- 2195663 TI - The national health care system in the welfare state. AB - The German national health care system has for some time shown signs of being in difficulty. Their manifestations are the overloading of the system in terms of consumer demand, the monopoly of functions, ascribed and acquired, by various groups of services providers, and the divided authority and obligations regarding health care and financing, between the federal government and the semi-autonomous German states and localities. At a deeper level of analysis it would appear that the underlying ideological themes that have guided the development of the national health care system need to be questioned. Alternative models of health care can rest on medical sickness models, as is currently the case, or on community centered health care, including primary prevention. The latter is based on the conviction and the insight that health and sickness is not an individualistic, autonomous, and independent set of phenomena but instead is a communal condition that needs to be addressed as such. The expected result is that health and sickness would be re-defined, along with professional intervention. PMID- 2195664 TI - Social work and the management of severe head injury. AB - This article examines the role of the health social worker in the management of the psychosocial sequelae of head injury from the membership perspective. Data relative to the incidence and medical dimensions of head injury and its psychosocial sequelae are briefly reviewed. The social work definition of head injury as a social process, rather than a medical event, is explored. Social work interventions designed to help those affected by head injury to manage home and community life are examined. PMID- 2195665 TI - Fear of cancer and knowledge of cancer: a review and proposed relevance to hazardous waste sites. AB - Cancer is a disease that is widely feared because of its prevalence and incidence, its widespread causes (heredity, environment, lifestyle) and the belief that 'everything causes cancer'. We review evidence on knowledge of cancer and find that knowledge is very limited. Then we examine factors that are related to knowledge of cancer and the pursuit of additional knowledge about cancer and factors that are related to health care behavior such as low rates of participation in cancer screening tests. This review leads us to conceptualize the essential, and perhaps central, role that fear of cancer has in the psychology of cancer. We then explore why cancer and fear of cancer have gained much attention in communities located near hazardous waste sites. PMID- 2195666 TI - [Clinico-immunologic aspects of diabetes mellitus]. PMID- 2195667 TI - [The contributions of ancient philosophers to the development of medicine]. PMID- 2195668 TI - [L.V. Gromashevskii and the beginnings of training in epidemiology in the USSR]. PMID- 2195669 TI - [A method of laser seromyotomy of the stomach]. AB - A technique of laser seromyotomy was developed as a method for vagus denervation for the treatment of gastroduodenal ulcers. Soviet Raduga neodymium YAG laser and foreign Medilaz and Flexilas units were employed as sources of laser irradiation. The operation was performed in the 'contact scalpel' mode with the use of Soviet sapphire tips. The developed technique permits seromyotomy that results in better hemostasis and lower risk of gastric submucosal layer involvement vs. electronomo suggested earlier by Taylor, an English surgeon. Twelve patients were operated on; one developed intraperitoneal hemorrhage that ceased independently. PMID- 2195670 TI - [The use of intravascular laser irradiation in surgery]. PMID- 2195671 TI - [Low-energy laser irradiation in surgery of the liver and biliary tract]. PMID- 2195672 TI - [The prospects of using helium-neon laser in postoperative suppurative complications in cancer patients]. PMID- 2195673 TI - [Use of visken in hypertension associated with ischemic heart disease and nutritional obesity]. PMID- 2195674 TI - [The value of echotomography in the planning of surgical treatment of liver cirrhosis]. PMID- 2195675 TI - [Basis for the evaluation of health care quality at the medical units of the health sector]. AB - A methodology for evaluating the quality of services rendered by the health institutions is presented. This methodology, proposed by the Basic Evaluation Group of the Health Sector, includes an operational diagnosis of the health care units, allowing the identification of service-rendering problems, this facilitating the elaboration of alternative solutions in the patient's best interests. It can be applied at all levels of the institutional hierarchy, from service and department levels to the macro dimension of health care. In order to obtain its best results, the methodology must be utilized systematically and continuously. PMID- 2195676 TI - [Evaluation of the medical care quality. Expectations of the patients and the workers of the medical units]. AB - Quality evaluation as a first step to improve health care is an essential step in the medical process. In the Mexican Social Security Institute (IMSS), this concern was first put into action in 1956, when a review of the medical records was undertaken at the La Raza hospital. The IMSS Medical Supervision Commission was formed in 1957, and in 1959 a medical auditorship was established. Until 1983 quality of care evaluation was centered on the information contained in the medical records. However, based on an extensive bibliographical review, the need to account for other aspects of medical care was then acknowledged, and attention was brought to issues such as the sufficiency and quality of the physical resources, availability and technical proficiency of human resources, supply of materials, organization of services, fulfillment of procedures according to current quality of care normativity, and optimization of results, all within a frame of humanitarian treatment of the patient. Quality of care can be viewed from three different angles: the patient's, the institution's, and the worker's standpoints. It has been customary to evaluate quality of care from the side of institutional expectations, unattending the other two viewpoints. In this study, a survey was made of 735 external patients, 853 hospitalized patients, and 1,353 workers, from 33 second and third level hospitals in both the federal District and the states, asking levels of satisfaction with the services provided. In the first group the highest percentage of dissatisfaction was related to medical information and doctor-patient relationship. In the hospitalization area the main problems were associated to food and attention by the social worker, but there were also problems in medical information, doctor-patient relationship, and patient orientation. Workers manifested dissatisfaction with wages and working area conditions, and asked for more institutional support and better motivations. PMID- 2195677 TI - [The concept of good medical care, 1933. By Lee RI and Jones LW]. PMID- 2195678 TI - The immunology of primary sclerosing cholangitis. PMID- 2195679 TI - The cellular immune response to nucleocapsid antigens in hepatitis B virus infection. PMID- 2195680 TI - Nature of autoantigens and autoantibodies in autoimmune hepatitis. PMID- 2195681 TI - Cellular mechanisms of hepatocyte damage and regulatory mechanisms in autoimmune chronic active hepatitis. PMID- 2195683 TI - Association of intracranial meningioma with arteriovenous malformation. AB - Simultaneous occurrence of a cerebral arteriovenous malformation and a primary brain tumor is rare. A case of a left occipital meningioma and a right parietotemporal arteriovenous malformation is reported. Clinical, radiological, and postmortem findings are described. Thirty previous reports of arteriovenous malformations associated with primary brain tumors are reviewed. In 18 cases the two lesions were intermixed or in close proximity. This spatial relationship between the lesions suggests more than a coincidental association. Several hypotheses are proposed to explain common causal connections. PMID- 2195684 TI - Charles Harrison Frazier: his influence on the development of early neurosurgery in America and on the development of the University of Pennsylvania School of Medicine. PMID- 2195682 TI - Autoantibodies in primary biliary cirrhosis. PMID- 2195686 TI - [50-year nightmare. Interview by Lars Peter Bergqvist]. PMID- 2195685 TI - Combined radiosurgery and external radiotherapy of intracranial germinomas. AB - Germinomas are successfully treated with radiation therapy; we have observed six cases that have been stereotactically irradiated by means of a linear accelerator (radiosurgery). In most cases a single dose of stereotactic irradiation effects the reduction of the tumor volume in a few days. External whole brain and, in two cases, spinal irradiation completed the treatment to avoid seeding of tumor cells. The technique and the advantages of this original therapeutical approach to intracranial germinomas are described and discussed. PMID- 2195687 TI - [In a class by itself]. PMID- 2195688 TI - [Koldingfjord--once steppingstone to nursing. Interview by Grethe Kjaergaard]. PMID- 2195689 TI - [The diagnostic potentials of studying the condensate of expired air]. AB - The author provides the reported data on the mechanisms of water and macromolecular compounds transport to the surface of the air ways. To diagnose moisture secretory function of the lungs, use is made of a new method of collecting expired air condensate. Quantitative and qualitative alterations in its biochemical composition, associated with respiratory diseases, are described. In the obstructive syndrome, the diminution of the condensate volume, changes in the concentration of biogenic amines, hormones and lipids contained by it are observed as is inhibition of the surface activity of surfactants. It is advisable that condensate collection may be performed on a wider scale for diagnostic and prognostic purposes. PMID- 2195690 TI - [Intravascular blood coagulation in diseases of the respiratory organs]. PMID- 2195691 TI - [The components reflecting the function of the connective tissue and of the protease-antiprotease system in lung pathology]. PMID- 2195692 TI - [The basic principles of rational chemotherapy in acute pneumonia]. PMID- 2195693 TI - [The definition and classification of bronchial asthma. Thoughts and proposals]. PMID- 2195694 TI - The general dentists's role in swallowing and speech aid appliances. PMID- 2195695 TI - [Alcohol--historical aspects]. AB - Alcoholic beverages have been produced already in a remote past. The recipe for distillated wine dates about 1100 A.D. Up to 1990 and longer, wine and alcoholic spirits were taken as an universal medicine. Alcohol has, moreover, socially integrative elements. Individual problems of alcohol abuse are as old as the production, but have become an epidemic problem with the pauperisation of the industrial proletarians in the 18th and 19th century, where private and government actions have been taken. PMID- 2195696 TI - [Biological changes caused by ethanol: their sequelae and importance in the diagnosis of alcoholism]. AB - Ethanol has profound effects on cellular function, causes hormonal imbalance and either directly or indirectly results in nutritional deficiencies. Together with genetic and environmental factors these metabolic changes eventually cause functional and structural damage to liver, heart, central nervous system and other organs. In order to prevent organ injury the early recognition of the alcoholic patient is important. The combination of physician interview, questionnaire and laboratory markers of ethanol abuse [MCV, GGT, AST and others] is useful for the diagnosis of alcoholism. Abstinence is the most important therapeutic measure. The treatment of organ damage has so far been symptomatic. Initial results of trials of specific treatment of alcoholic liver disease are encouraging. PMID- 2195697 TI - [Diagnosis and treatment of alcoholism: psychiatric aspects]. AB - The image of the chronic alcohol patient has changed. Diagnosis is only possible if the doctor assumes alcohol abuse in all his patients. The diagnosis can only be made taking psychiatric, somatic and psychosocial aspects into consideration. Because of the tendency of the patient to deny, an independent history is necessary. Questionnaires, such as the 'Munchner Alkoholismustest', may be helpful. Therapy by the family physician is initiated with a careful somatic, psychiatric and psychosocial work-up, counselling and care. An important factor is the close collaboration between physician and social worker. PMID- 2195698 TI - [Ambulatory, disulfiram-(Antabuse)-assisted management of the alcoholic patient]. AB - The treatment of patients suffering from alcoholism is notoriously difficult. Ambulatory supportive therapy using disulfiram and supervised by the practicing physician has many advantages. Foremost among these is the maintenance of the patient within his working and social environment. For achievement of longterm abstinence, psychological aspects (patients motivation and agreement, understanding care by the physician) may be more important than the aversive effects of disulfiram. Although disulfiram is generally a safe drug, careful preliminary work-up represents the key to proper assessment of risk versus benefit. PMID- 2195699 TI - [To your health, a toast to you, colleague...]. AB - Using a medical district association meeting as an example, the problem of 'alcohol and doctors' is considered. According to numerous authors, doctors belong to a special alcohol risk population, although hardly anyone else is better acquainted with the risk of alcohol. With some courage and improved knowledge of the problem, one should be able to prevent a friend or a colleague from excessive alcohol abuse. The prognosis is by no means bad. PMID- 2195700 TI - [Considering the psychotropic effect of alcohol]. AB - The use of alcohol--one of the oldest drugs of mankind--has positive and negative effects in our societies which are related to the psychotropic actions of this substance. Alcohol exhibits an astonishingly broad spectrum of psychopharmacological effects, including anxiolytic, sedative hypnotic and stimulating euphoric components. Accordingly, alcohol affects all major neurobiological systems. Nevertheless, the psychopharmacological action varies from one individual to another. With biological markers, the recognition of differences in susceptibility to alcohol, such as a genetic predisposition to alcoholism, is attempted or indicators of abusive alcohol consumption are sought. Existing biological markers, however, are not yet specific for certain psychopharmacological actions sought by patients in a self medication process. Some possible implications of new biomedical findings for alcohol policy are discussed. PMID- 2195701 TI - [Psychiatric patients in private care. Historical analysis from a municipality in western Norway]. AB - Radoy, an island (4,500 inhabitants) in Western Norway, has traditionally accepted many psychiatric patients for care in foster homes. Since the end of the 19th century, 855 patients placed in foster homes have been registered. Only 7% of these were original inhabitants of Radoy. The mean duration of stay was 13 years (median: 9). The tendency has been towards longer periods of stay, older patients, an increasing number of female patients, and more schizophrenic patients. It takes on average nine months (median: 5) after cancellation of the foster contract before the patient receives alternative accommodation. The waiting period for a place in a nursing home is especially long. This problem must be solved if care in a foster home is to be a suitable alternative in the future. PMID- 2195702 TI - [Cognitive therapy. Methods and applications]. AB - Cognitive therapy is a fairly new form of psychotherapy. The article compares this form of therapy with the more common psychodynamic oriented psychotherapy on the one side and behavioural therapy on the other side. The authors define the most common terms in cognitive therapy (basic beliefs and automatic thoughts), and describe the content of the therapy. Finally they outline the areas where cognitive therapy has been proven most beneficial (treatment of depression, anxiety states, chronic pain, psychosomatics and increase in patient compliance), and discuss the future use of cognitive therapy in Norway. PMID- 2195703 TI - [Survey of growth hormone deficiency in children]. AB - When other causes of retarded growth have been ruled out, investigation for classic growth hormone deficiency is indicated in children with reduced velocity of growth and retarded bone development. In cases of classic growth hormone deficiency there is insufficient increase in growth hormone levels after two stimulation tests. However, some short children whose stimulation tests are normal but whose spontaneous growth hormone secretion is reduced or pathological may possibly benefit from growth hormone treatment. Therefore measurements of spontaneous growth hormone secretion and insulin-like growth factor IGF-1 have also been used in the diagnosis of growth hormone-related short stature. The authors present a overview of the diagnosis of growth hormone deficiency in practice based on their own experience. PMID- 2195704 TI - [Effect on the lipid profile of diet supplemented with fish oil concentrate]. AB - Effects on serum lipids were examined in a double blind placebo controlled trial including 111 male and females with cholesterol values higher than 7.0 mmol/l. The patients were treated with 6 g Almarin capsules consisting of the highly concentrated fish-oil EPAX 6000 EE in a daily dose corresponding to 2.1 g eicosapentaenoic acid and 1.5 g docosahexaenoic acid, or olive oil control for 12 weeks. We registered the effects on serum triglycerides, total cholesterol and HDL cholesterol. Compared with baseline values a 19.5% median reduction in serum triglycerides could be observed in the n-3 treated group. This reduction was significantly different from control and baseline values. We also observed a favourable trend towards lower total serum cholesterol and higher serum HDL cholesterol. PMID- 2195705 TI - [Irreversible ischemic myocardial damage. Physiopathologic aspects of ischemia and myocardial revascularization]. AB - A substantial amount of research has been focused on the mechanism of irreversible ischemic cellular damage. An irreversibly damaged cell cannot restore normal function when reperfused. During ischemia the cellular level of high energy phosphates decreases, which induces a rise in the cytosolic level of free calcium. An elevated level of cytosolic calcium is probably harmful to the myocyte, partly because calcium activates proteases and phospholipases. Reperfusion of an ischemic myocyte disturbs cellular ion control, increases cellular volume, induces mechanical stress on cellular membranes and produces free oxygen radicals. Thus, the cause of irreversible injury during ischemia and reperfusion probably includes several factors. Knowledge about these mechanisms will hopefully provide new therapeutic options. PMID- 2195706 TI - [Children in distress]. PMID- 2195707 TI - [Intravenous abuse of crushed tablets. A case with fatal outcome]. AB - We present a case of fatal vascular destruction and granulomatosis of the lungs from intravenous injections of dissolved tablets containing microcrystalline cellulose as filler material. Numerous microcrystalline cellulose pulmonary emboli and foreign body granulomas were detected, and the pulmonary parenchyma showed signs of disturbed circulation with focal necrosis and oedema. PMID- 2195708 TI - [Pivampicillin (Pondocillin) and pivmecillinam (Selexid) can result in carnitine deficiency]. PMID- 2195709 TI - [George S. Nelson. Charismatic lecturer in tropical medicine]. PMID- 2195710 TI - [Biotechnology in perspective]. AB - Biotechnology is a collective term for a large number of manipulations of biological material. Fields of importance in stock-keeping include: (1) manipulation of reproductive processes; (2) genetic manipulation of macro-(farm) animals and micro-organisms and (3) manipulation of metabolism. Fitting in biotechnological findings in breeding-stock farming has repercussions in several fields such as the relationship between producers and the ancillary and processing industries, service industries, consumers and society as a whole. The use of biotechnical findings will also require further automation and adaptation of farm management. Biotechnology opens up a new area and new prospects for farm animal husbandry. These can only be regarded as positive when they take a permanent development of the entire section into account. PMID- 2195711 TI - Mosaicism in the mouse trophectoderm. AB - The issue of mosaicism in the mouse trophectoderm is examined by reviewing two sets of evidence: one arguing for a mosaic, the other for a non-mosaic character. Evidence for mosaicism includes documented cellular contribution from the inner cell mass to the trophectoderm, and data that reveal the gradual pace of the allocation process that separates the inner cell mass and trophectoderm lineages. Evidence suggesting a non-mosaic character for the trophectoderm is based on the polarization process undergone by exterior cells in the eight-celled embryo, the heritability of the changes brought about by this process, and the formation of gap junctions between the resulting apolar, trophectoderm progenitor cells. Since inner-cell-mass cells are developmentally labile, spatially heterogeneous and translocate to the polar trophectoderm, it is concluded that the polar trophectoderm is a mosaic tissue. PMID- 2195713 TI - Update and clarification on reimbursement of nurse practitioners by Medicare Part B in Wisconsin. PMID- 2195712 TI - Forces of change--an overview. PMID- 2195714 TI - Placebo-controlled trial of nimodipine in the treatment of acute ischemic cerebral infarction. AB - Nimodipine is a 1,4-dihydropyridine derivative that shows a preferential cerebrovascular activity in experimental animals. Clinical data suggest that nimodipine has a beneficial effect on the neurologic outcome of patients suffering an acute ischemic stroke. Our double-blind placebo-controlled multicenter trial was designed to assess the effects of oral nimodipine on the mortality rate and neurologic outcome of patients with an acute ischemic stroke. One hundred sixty-four patients were randomly allocated to receive either nimodipine tablets (30 mg q.i.d.) or identical placebo tablets for 28 days. Treatment was always started less than or equal to 48 hours after the acute event. The Mathew Scale, slightly modified by Gelmers et al, was used for neurologic assessment. Mortality rate and neurologic outcome after 28 days were used as evaluation criteria. We considered 123 patients to be valid for the analysis of efficacy. Mortality rates did not differ significantly between groups. Neurologic outcome after 28 days of therapy did not differ between groups. However, when only those patients most likely to benefit from any intervention (Mathew Scale sum score of less than or equal to 65 at baseline) were analyzed separately in post hoc-defined subgroups, the nimodipine-treated subgroups showed a significantly better neurologic outcome. This result suggests that some patients with acute ischemic stroke will benefit from treatment with nimodipine tablets. PMID- 2195715 TI - Ischemic stroke due to protein C deficiency. AB - Plasma protein C exerts anticoagulatory effects by inactivating factors V and VIII. Hereditary protein C deficiency is transmitted as an autosomal dominant disorder. Homozygous individuals usually develop purpura fulminans as newborns; heterozygous protein C-deficient individuals are at increased risk for venous thrombosis and pulmonary embolism. However, arterial thrombosis has been only rarely observed. We describe a young patient with heterozygous protein C deficiency who experienced a severe stroke due to thrombotic occlusion of the left middle cerebral artery. PMID- 2195716 TI - A review of stroke rehabilitation and physiotherapy. AB - Most of the members of the therapeutic team in stroke rehabilitation take the effectiveness of physical treatments after stroke for granted. Yet, published data show that the evidence is not so straightforward or easy to evaluate. The majority of the hard evidence, however, does imply that stroke patients benefit from rehabilitation with physiotherapy. This benefit may be statistically small, but for a given individual, it could mean the difference between living at home or in an institution. Few studies address the question of the optimal physiotherapy in stroke rehabilitation. The evidence available today suggests that it does not matter which form of treatment is chosen and that any of the available approaches will improve the patient's functional status. In other words, if an optimal treatment exists, we have, so far, failed to identify it. Until further evidence emerges, we should therefore select therapies that are most cost-effective and that can be given to the largest number of patients. Well planned clinical trials aimed at finding the best approach and discriminating potential responders from nonresponders are urgently needed. PMID- 2195717 TI - Free radicals in central nervous system ischemia. PMID- 2195718 TI - Animal stroke models. They are relevant to human disease. PMID- 2195719 TI - Evidence for prostaglandin mediation of the stimulation of luteinizing hormone releasing hormone release by calf thymus extract. PMID- 2195721 TI - Hospitals and the public purse. PMID- 2195720 TI - Tin and the thymus gland: a review. AB - Experimental studies over the last decade have suggested an association between thymus immune and homeostatic function and exogenous tin. It has been hypothesized that the thymus gland synthesizes and secretes one or more tin bearing factors that enhance immune defenses against malignancy and retard the gradual loss of immune capacity with senescence. This review conciliates data from several divergent areas of research in order to explore the rationale for the above concepts. PMID- 2195722 TI - A randomized trial of the immunosuppressive efficacy of vincristine in cardiac transplantation. AB - We evaluated the efficacy of the addition of the lymphoblasticidal agent vincristine to standard immunosuppression in heart transplantation in a prospective randomized study of 92 patients (46 to receive and 46 to not receive vincristine) with a follow-up period of 12 months. Patients received either equine antithymocyte globulin for the first week or OKT3 monoclonal antibody (OKT3) for the first 10 or 14 days after transplantation. Six to eight doses of vincristine were given over 9-12 weeks, beginning 2 days after completion of ATG or OKT3. The number of rejection episodes in the first six months posttransplantation, the percentage of patients corticosteroid maintenance-free at one year, cumulative immunosuppressive drug doses, deaths, infections, and neuropathy were followed. The addition of vincristine resulted in more patients achieving corticosteroid maintenance-free status at one year (vincristine 68%, no vincristine 38%, P = 0.01). In comparing patients at relatively high risk for rejection (those younger than 55 years and all females) with those at relatively low risk (males older than 55 years), only the high-risk vincristine-treated patients showed significantly fewer rejection episodes and a higher corticosteroid maintenance status at one year (66% vs. 32%, P = 0.01). There were no significant differences in survival (vincristine 96%, no vincristine 98%), infection, or amounts of other immunosuppressive agents used. The major side effect was neuropathy, which occurred more frequently in the vincristine-treated group (43% vs. 18%, P less than .001). We conclude that vincristine acts as an immunosuppressive agent in cardiac transplantation, particularly in patients at higher risk for rejection. PMID- 2195723 TI - Turbo-screening of bacterial colonies using microwave denaturation on paper filters. PMID- 2195724 TI - Catalytic RNA and the origin of genetic systems. AB - The recent discovery of catalytic RNA molecules has provoked enormous interest in the origin of life and has given rise to new speculations about how living systems developed on the primitive earth. Here we outline why the discovery of catalytic RNA molecules has profound evolutionary implications, and then go on to discuss models for the emergence of metabolic complexity and protein synthesis in a primitive 'RNA world', emphasizing the constraints imposed on such models by genetical arguments. PMID- 2195725 TI - Centromeres of budding and fission yeasts. AB - Centromeres of the budding yeast Saccharomyces cerevisiae are structurally relatively simple, are specified by only about 125 base pairs of DNA, and contain no repeated DNA sequences. The centromere regions in the fission yeast Schizosaccharomyces pombe span many kilobase pairs of DNA and contain repeated DNA sequences that appear to be necessary for full centromere function. A portion of the repeated sequences is organized into a large inverted repeated structure in the centromere region of each S. pombe chromosome. Fission yeast provides an excellent model system for studying the role of repeated DNA sequences in centromere function. PMID- 2195726 TI - [The effect of transforming growth factor beta on the intensity of cellular DNA synthesis in relation to the type and conditions of cultivation]. AB - A study was made of the influence of transforming growth factor beta (0.05-50.00 ng/ml) on the intensity of 3H-thymidine incorporation in the DNAs of pseudonormal mouse fibroblasts of NIH 3T3 line, of cells of NRK-49F line from normal rat kidney, and of cells of A-549 line from human lung adenocarcinoma. The experiments were carried out in the absence and in the presence of epidermal growth factor (5 ng/ml), and(or) insulin (1 micrograms/ml), as well as in the presence of different concentrations of fetal calf serum, and while using different time of incubation of cells with the above mentioned growth factors. It was shown that depending on the culture conditions the transforming growth factor beta exerted stimulatory, inhibitory or no action on the intensity of DNA synthesis in the cells of the same type. An attempt was made to analyse the reasons, which may significantly determine the direction of regulatory influence of the transforming growth factor beta on DNA replication in the cells. PMID- 2195727 TI - [Meiotic chromosomes of the spermatocytes ejaculated by bulls]. AB - The Sperling and Kaden (1971) approach was used in studies of the bull meiotic chromosomes. The number of meiocytes in the ejaculates of normal bulls ranged from 0.0001 to 0.0114% of the whole set of cellular elements in the ejaculate. Two of the studied bulls had a chromosomal abnormality in somatic cells (60, XX/60, XY mosaic). These bulls displayed no deviation as concerns the quantity of meiocytes in their ejaculates. In two other bulls examined, with cryptorchism and azoospermia, about 0.0017 and 4.75% meiocytes were counted in the ejaculate, respectively. A comparative analysis of ejaculated chromosomes and meiotic chromosomes obtained from the normal testes by biopsy did not reveal any differences in the chromosomal morphology. Various premeiotic and meiotic stages, from spermatogonium A and B to metaphase 1, were identified in the bull ejaculates. This technique may be valuable in cytogenetic diagnosis of meiotic abnormalities in sires. PMID- 2195728 TI - Extra-adrenal non-functioning paraganglioma. AB - Extra-adrenal non-functioning retroperitoneal paragangliomas are rare tumors. We herein report a case of retroperitoneal tumor which posed a diagnostic and management problem. Review of the literature shows only 16 previously reported cases of extra-adrenal paraganglioma which underwent complete surgical excision. PMID- 2195729 TI - Prognostic factors in stage IV ovarian carcinoma treated with platinum-based regimens. AB - Eight factors were analyzed for prognostic significance in univariate analyses in a series of 76 women with stage IV ovarian carcinoma treated with combination chemotherapies including cisplatin or carboplatin. The clinical objective and pathologic complete response rates were 51.2% and 27.3%, respectively. Median overall survival and progression-free survival were 15 and 7 months, respectively. No variables reached statistical significance. Trends toward better survival were noted for grades 1 and 2 for the adriamycin-containing regimen. Using progression-free survival as an end point, significant prognostic factors included complete clinical or pathologic response. Our data confirm that the standard approach is unlikely to modify the clinical outcome of stage IV ovarian cancer. New treatment modalities including high-dose-intensity regimens and neo adjuvant chemotherapy delivered before surgery could improve clinical results. Moreover, biologic characterization of ovarian tumors may provide information to design specifically targeted treatment. PMID- 2195730 TI - [Metabolism of methylglyoxal and malignant neoplasms]. AB - The present notions on the metabolism of methylglyoxal, an endogenic controller of cellular proliferation, are adduced. The interaction between metabolism of methylglyoxal and that of carbohydrates, proteins and lipids is demonstrated. The metabolic chart has been worked out and enzymes catalyzing methylglyoxal metabolic reactions are determined. The effect of methylglyoxal and its bisguanylhydrazones derivatives on the processes of cellular proliferation control has been examined. PMID- 2195731 TI - [Extracellular adenosine triphosphate, its sources and the effect on animal cell functions]. PMID- 2195732 TI - [Changes in the proteolytic activity of tissues during aging]. AB - The intensity of proteolytic processes and qualitative composition of autolysis products of the brain, liver and testicle tissues of young and old rats were studied. The gel-chromatographic analysis (Sephadex G-15 and G-50) revealed no considerable amount of high-molecular peptides (1500 Da and over) before and after autolysis. The measurement of the quantity of free amino groups in the gel chromatographic fraction after the complete acid hydrolysis has confirmed that result. The low-molecular peptides and free amino acids, are the main products of the tissue autolysis. The intensity of proteolytic processes, determined by an increase in the amount of amino acids depends on the autolysis duration and age of animals. The total increment of amino acids in the brain and liver tissues of old animals for the first hour of autolysis has been higher by 102 and 219% as compared to young ones. The autolysis of testicles of the young and old animals after the first hour of incubation is characterized by the same intensivity. Such a regularity is not revealed when analyzing the same processes by the Lowry method. PMID- 2195733 TI - [Standardized treatment]. AB - Treatment protocols have not been well-defined, and may comprise anything from mere instructions regarding simple procedures to guide-lines for the treatment of the whole course of a disease. The discussion about treatment protocols has continued on since the 70's, and the system has been introduced into the Health Service of a number of countries. Those in favour of the programmes have focused, in particular, on the economic advantages and the advantage of achieving a certain quality of treatment, while those opposing the programmes insist that clinical freedom is at stake. We have found, especially via literature studies, that little knowledge is available as to what extent treatment protocols or case management protocols are employed, e.g., in Sweden and the USA where there have been a number of advocates of these systems. We have only been able to find two evaluation studies of more comprehensive programmes. In these two studies, the total expenditure for treatment was not clearly reduced, and as there were no well-defined parameters for quality of care, it has not been possible to demonstrate any improvement in the quality itself. It is, of course, possible that the discussion in respect of treatment protocols has indirectly had an effect on clinical thought, including those countries where these systems have not been introduced. PMID- 2195734 TI - [Immunosuppression with cyclosporin induces clinical remission and improved beta cell function in patients with newly diagnosed insulin-dependent diabetes. A national and international multicenter study]. AB - A prospective, randomized, double-blind, placebo-controlled international multicenter trial including 188 newly diagnosed insulin-dependent diabetic (IDDM) patients was undertaken with the aim of investigating whether immunosuppression for one year with ciklosporin (Cs) could induce and maintain clinical remission and improvement of beta-cell function. The relative odds for non-insulin requiring remission at one year were increased approximately five times in the Cs treated group. After three months Cs-treated patients achieved more than a doubling of beta-cell function compared to baseline than did placebo-treated patients, and the Cs-treated group maintained this improvement in beta-cell function for 12 months, whereas the placebo-group lost beta-cell function during the same period. Short duration of disease (less than or equal to six weeks of symptoms, less than or equal to two weeks of insulin treatment) was associated positively with remission, as was an elevated proinsulin/C-peptide ratio, especially in patients with the tissue-type HLA-DR 3,4; 4,X and X,X. Cs-treatment inhibited the formation of antibodies against insulin and islet cell components, but islet cell antibody status at entry was not predictive of remission. Cs treatment caused a reversible decrement of kidney function as measured with serum creatinine and the calculated creatinine clearance, but studies of renal physiology and kidney biopsies performed on a limited subset of patients indicated that Cs treatment in IDDM patients for one year induced a slight chronic nephropathy in some of these.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2195735 TI - [Surgical treatment of abdominal aorta aneurysm 1983-1987. A multicenter study. 1266 operations, development and early results]. AB - During the years 1983-1987, 1,266 operations for abdominal aortic aneurysm (AAA) were carried out in eight surgical departments with vascular surgical function. The activity increased constantly corresponding to 311 patients in 1987 or 50% more than in 1983. During this period the distribution between patients subjected to elective operation and those operated upon as emergencies was very uniform. In the latter group, only a slight increase in the number of AAA patients with rupture was observed. The risk of complications was low with a significant decrease in the need for dialysis. The early mortality was constant for the patients subjected to elective operation remained constant about 5.5%. A marked decrease in the early mortality was observed for the patients operated upon as emergencies with rupture from 63 to 50% and without rupture from 37 to 25%. At the conclusion of the period, ultrasonic scanning became the preoperative investigation of election and introduction of an aortic prosthesis the method of operation of election. Patients with AAA should be recognized so that elective surgery can be offered before a condition endangering life develops. PMID- 2195736 TI - [Somatomedins (insulin-like growth factors), growth hormone and chronic liver disease]. AB - Somatomedins or insulin-like growth factors (IGF) are peptides synthesized in the liver. IGFs have different anabolic and metabolic actions and are important in normal growth and development. The concentration of IGF is low in patients with chronic liver disease mainly due to the decreased liver function. Low levels of somatomedins are also seen in patients with growth hormone (GH) insufficiency, renal impairment and malnutrition. GH stimulates the production of IGF-1, and both are part of a negative feed-back system acting on hepatic, pituitary and hypothalamic levels. The basal and stimulated GH concentration is pathologically elevated in patients with chronic liver disease. The total daily secretion is unknown as urinary measurements have only recently been introduced. Alterations in liver IGF receptors in patients with chronic liver disease require still investigation as they may be important for the liver function. PMID- 2195737 TI - [Stereochemistry--an overlooked problem in medical treatment and research]. AB - On the background of marketing of an increasing number of drug racemates with the subsequent problems for medical treatment and research, a short review is given focusing on the optic isomery and the significance of optic isomeric drugs for medical treatment and research. Different problems, which may arise in relation to the use of drug racemates are mentioned. The racemic problem is elucidated by examination of and reference to existing studies on drug racemates including studies on pharmacodynamic and pharmacokinetic properties of pure (+) and ( )enantiomers. As the receptor systems of the organism and the process of drug metabolization are stereoscelective, the ideal demand to drug racemates should be that they are regarded as two different drugs until investigations have clarified the degree of pharmacodynamic/pharmacokinetic differences between the (+) and ( )enantiomer. Whether the single enantiomer should be preferred to the racemate may be difficult to decide and may require considerable research, but solution of this can, on the other hand, give valuable advances in drug treatment, for instance in form of drugs with more selective and fewer side effects. PMID- 2195738 TI - [The treatment of hydrocele]. PMID- 2195739 TI - Echographic tissue characterization in diffuse parenchymal liver disease: correlation of image structure with histology. AB - Seventy livers were examined in vitro using a computerized ultrasound B-mode data acquisition and analysis system. For tissue characterization, statistical parameters from pattern recognition algorithms describing image brightness and image structure were used. Reference classification based on histopathology as well as on chemical/morphometrical analysis led to the diagnostic classes of normal, fatty liver, fibrosis/cirrhosis and fatty fibrosis/cirrhosis. Comparing the two reference methods for ultrasound tissue characterization, reclassification based on chemical/morphometrical analysis resulted in a significant increase in diagnostic accuracy. The strong correlations between statistical ultrasound image parameters and morphometrical features reflect the relevance of our statistical approach to ultrasound tissue characterization. PMID- 2195740 TI - Computerized ultrasound B-scan texture analysis of experimental fatty liver disease: influence of total lipid content and fat deposit distribution. AB - Statistical pattern recognition procedures allow a quantitative description of ultrasound-B-scan image texture. According to well-established animal models, different types of fatty liver disease were induced in female Wistar rats. For the correlation of the computerized ultrasound image with its underlying histology a variable tissue model based on histomorphological data, texture analysis of the histological image and biochemical measurements of total lipid, water and hydroxyproline content was created. Whereas a regional arrangement of large fat deposits leads to a significant increase in the "mean grey level" (measure of image brightness) of the ultrasound-B-scan image, there is no difference in image brightness between normal liver tissue and liver steatosis for the tissue model with diffuse homogeneous fatty infiltration. It is demonstrated by multiple linear regression analysis that the "mean grey level" of the ultrasound-B-scan image depends not only on total lipid content but even more on the histomorphological fat deposit distribution. PMID- 2195741 TI - Partially coherent transducers: the random phase transducer approach. AB - Ultrasound speckle is a consequence of the stochastic nature of the reflectivity of scattering media (e.g., biological tissue) and of the coherent nature of piezoelectric transducers. This speckle noise can be reduced by the use of incoherent processing techniques (e.g., spatial compounding, incoherent summation, random phase and phase insensitive transducers). We present a unified framework that explains the limitations of incoherent processing in terms of the information grain theory. This theory predicts the gains in SNR as well as the losses in directivity. We also present the random phase transducer approach to incoherence to total coherence. We present applications to speckle reduction, detection of specular reflectors, attenuation estimation and ultrasound imaging. We show that totally incoherent transducers completely remove diffraction effects. They might be used in attenuation estimation, in which case, correction for diffraction is no longer required, in order to obtain unbiased estimates. Partially coherent transducers might also be useful in imaging to reduce speckle noise. PMID- 2195742 TI - Aminoglycosides in urology. PMID- 2195743 TI - Infected urachal cysts. AB - Infected urachal cysts present with protean clinical manifestations. Diagnosis is frequently difficult in spite of the use of modern genitourinary radiologic imaging techniques. Patients with intra-abdominal or pelvic symptoms are frequently misdiagnosed. Surgical excision is the treatment of choice for infected urachal cysts. PMID- 2195744 TI - Establishment of new human prostatic cancer cell line (JCA-1). AB - The establishment of a new human prostatic cancer cell line is described. This cell line was derived from a poorly to moderately differentiated prostatic adenocarcinoma. It has been maintained in tissue culture for fourteen months and has been passed fifty-two times. This cell line has an ability to form colonies in soft agar suspension cultures, and also is transplantable to nude mice. Tumors grown in nude mice revealed a poorly differentiated adenocarcinoma with positive PSA staining. Acid phosphatase activity was detected in freeze-thawed cells by enzymatic assay. A karyotype analysis demonstrated aneuploidy with a model chromosomal number of 69 and six marker chromosomes. PMID- 2195745 TI - Carcinoma of prostate metastasizing to vocal cord. AB - Metastatic involvement of the larynx by carcinoma of the prostate is a rare event: only 5 cases are recorded in the English literature. We report a case of prostatic carcinoma with symptomatic metastasis to the right vocal cord. Five months after the diagnosis of metastatic disease in the vocal cord the patient died of widespread metastases. We report the sixth case of this event and review the reported cases in the literature. PMID- 2195746 TI - [A method of closed iridoplasty in transparent crystalline lens]. AB - The operation is performed through two punctures of the cornea with the normal depth of the anterior chamber artificially maintained with physiologic saline supplied via a flat cannula. Through a corneal puncture this cannula is brought under the contralateral edge of iridal defect, elevating this defect beyond the lens, and a needle brought via the other puncture pricks the iris and the needle tip enters the cannula canal. The needle and cannula joined together are brought to the second edge of iridal defect, similarly pricking it, and brought out of the anterior chamber, still joined together. Then the needle is brought back through the same corneal puncture, so that it joins the cannula brought through the other corneal puncture, and brought from the anterior chamber. The stitch is tied on the cornea, with the iris being tightened. PMID- 2195747 TI - [New reconstructive surgery in traumatic detachment of the ciliary body with recession of the angle of the anterior chamber]. AB - Penetrating wounds of the corneoscleral area are remarkable for particularly severe course of posttraumatic period, this being explained by direct injury to the ciliary body, impaired anatomic relationships in the anterior chamber corner, formation of this corner recession, this resulting in detachment of the ciliary body and development of the hypotonic syndrome. The authors suggest a new surgical technique of reconstructing the anterior chamber corner in its recession and detachment of the ciliary body with the aim of correcting the hypotension and fortifying the ciliary body at the site of its anatomic localization. This method was used in the treatment of 32 patients with subatrophy, detachment of the ciliary body, and hypotension; positive effect was achieved in 28. PMID- 2195748 TI - [Drug therapy of progressive myopia]. AB - To stabilize weak and medium-severity progressive myopia, instillations of cycloplegics (homatropin or tropicamid) and of hypotensive agents (clofelin or thymolol) were administered into the conjunctival cavity once a day (at bedtime). The course of treatment lasted 30 days and was repeated every 2-3 months. Complete stabilization of myopia was achieved in 65-58% of cases, as evidenced by a follow-up of 3 years, on an average. Incomplete stabilization of the condition was observed in 35-42% of patients, the annual progress gradient being above 0.15 diopters. Simultaneously an accumulation of the relative accommodation reserves was observed, by 38.3% on an average, and a resolution of asthenopia. In a reference group of 50 subjects (100 eyes) spontaneous stabilization took place in 27% of cases, the relative accommodation reserve being unchanged. PMID- 2195749 TI - [A new enriched balanced irrigation solution for intraocular surgery (experimental study)]. AB - Experimental trials of a new intraocular irrigation solution, one of the enriched balanced salines, were carried out. A comprehensive morphologic study has revealed the protector characteristics of lactosol plus (lactosol + taurin) used in the management of irrigation injury to the posterior epithelium of the cornea in the course of experimental intrachamber perfusion. The protective properties of lactosol + taurin, a new enriched balanced saline, are explained by the similarity of its chemical composition to that of the intraocular fluid and by the presence of a stable polyfunctional bioprotector, taurin amino acid. PMID- 2195750 TI - [Eximer lasers in ophthalmologic surgery (review of the literature)]. PMID- 2195751 TI - [Repeated anti-glaucoma filtering surgery (review of the literature)]. PMID- 2195752 TI - Orthopaedic problems in old dogs. AB - With advancing years a dog may suffer from a variety of conditions of its musculoskeletal system which adversely affect its ability to exercise and may cause it to be retired from activities in work and sport for which it has been trained. Arthritis is common, and in many cases arises from developmental errors suffered in puppyhood, such as hip dysplasia, osteochondrosis and growth plate disorders. Trauma to joints (ligament ruptures, dislocations and fractures) may also be the precursor of degenerative joint changes later in life. It is important, therefore, for all such conditions to be corrected as effectively as possible if joint disease is to be minimised as the dog grows older. Preventive action is also required for some conditions for which correction may not be entirely feasible, so the identification of modes of inheritance is important if those are to be controlled by breeding. Certain spinal disorders also tend to increase in prevalence with age, particularly spondylosis deformans, neoplasms and chronic degenerative radiculomyelopathy. As it happens, spondylosis in mild to moderate degree affects pet dogs very little, but a reduction in spinal flexibility can cause problems for dogs required to be agile in work or sport. In common with other body tissues, neoplasm of the locomotor system increases in occurrence in older dogs, and although the overall incidence of tumours of bones, joints, nervous tissue and muscle is relatively low, these are the most serious of all the limb and spinal conditions encountered because of their life threatening propensities. The treatment required covers a wide range from simple changes of management in order to reduce exercise, to the use of analgesics and anti-inflammatory drugs and to surgery to remove diseased tissue, stabilise joints or reduce pain with forms of arthroplasty or arthrodesis. PMID- 2195753 TI - Skin diseases of old dogs and cats. AB - The ageing process tends to predispose dogs and cats to certain skin diseases. Impaired immunosurveillance is believed to render the animals more susceptible to neoplasia which can affect any organ including the skin. Endocrinopathies are also more common in older animals. There are some diseases of internal organs which can affect the skin, and some of these tend to occur with increased frequency in old animals. Finally, seborrhoeic diseases are either more common in older animals, or become increasingly severe with age. PMID- 2195754 TI - Antibody response to experimental Salmonella typhimurium infection in chickens measured by ELISA. AB - An indirect ELISA has been developed to detect Salmonella typhimurium antibodies in chicken sera, using whole bacterial cell protein, flagellar protein or lipopolysaccharide as antigens. In experimental infections high concentrations of S typhimurium-specific IgG persisted after the faecal excretion of S typhimurium had ceased, whereas the specific IgM response was transitory. Some uninfected chickens placed in contact with experimentally infected birds developed high IgG titres in the absence of detectable faecal excretion. Other S typhimurium strains, which varied in their invasive abilities, also induced high titres of IgG. The ELISA allowed chickens infected experimentally with S typhimurium to be differentiated from chickens infected with 10 other serotypes, including S enteritidis. The use of whole blood in place of serum in the ELISA reduced the titres slightly. The storage of serum dried on to filter paper strips for four weeks produced little change in ELISA antibody titre, and the treatment of such strips with phenol or chloroform vapour had little or no effect on the antibody titre. PMID- 2195755 TI - Nephropathy in young lambs. AB - Renal disorders in lambs may be congenital, infectious, toxic, immunologically mediated or secondary to urethral obstruction. Congenital abnormalities are uncommon. Kidney infections often are only one aspect of more widespread diseases, for example, tick pyaemia or salmonellosis. Toxic diseases, which affect mainly the renal tubules, may be caused by bacterial, chemical or plant toxins, although in lamb nephrosis the cause is unknown. Immunecomplex glomerulonephritis is uncommon, and one form, mesangiocapillary glomerulonephritis of Finnish landrace lambs, is under genetic control. Urolithiasis may have secondary effects on the kidneys. PMID- 2195756 TI - Improving food quality through new technology. AB - New technological developments make it possible to improve the quality of animal disease therapy, prophylaxis and diagnosis, and to improve animals' growth and fertility. The term 'quality' includes not only objective measurements, such as the fatness or leanness of meat, but also organoleptic factors such as flavour and others which are of increasing importance to consumers, such as animal welfare. Is new technology consistent with the improvement of quality? For example, beta-agonists and porcine somatotrophin reduce the fatness and increase the protein content of carcases, but there are also subtle positive relationships between fatness and eating quality. In contrast, bovine somatotrophin appears to have no effect on milk composition but there are indications that it may affect the perception of milk quality by some consumers. Improved vaccines can increase food quality by improving animal health and welfare and increasing the uniformity of the product; immunological techniques may also be used to improve meat quality. A gulf has developed between the benefits from new technology and consumer perceptions; indeed there is evidence of political resistance to some technological advances. Despite the stringent regulation of veterinary medicinal products in the United Kingdom and other countries, there is continued pressure for greater political control over their approval. The exchange of information between scientists, industry, the legal regulators and consumers must be improved so that advances in technology are acceptable to the majority and used to the advantage of all. PMID- 2195757 TI - Enterohaemolysin and Shiga-like toxin genes in E coli. PMID- 2195758 TI - [Diagnosis of tumors of the bladder and rectum by the method of high-resolution transvaginal echography]. AB - Analysis of the results of high resolution transvaginal US-tomography in 32 women with malignant bladder and rectal tumors made it possible to assess the potentialities of this new method for the diagnosis of a degree of local spreading of these tumors. As compared to transabdominal echography UST proved to be more informative in tumors of the cervix, basis and anterior wall of the bladder and in calcifications on the tumor surface which were detected in 3 patients. Transvaginal US-tomography with a contrast study of the rectal walls provided good diagnostic information on a degree of local spreading of malignant rectal tumors. The transvaginal approach showed its advantages in noticeable tumor stenosis of the rectum. Tumor assessment in 3 women with stenosis was made possible owing to this method. PMID- 2195759 TI - [The ultrasonic picture of hypernephromas]. AB - For objective assessment of an ultrasound picture of the kidneys in tumors the authors compared the results of USI, angiography of the kidneys and the removed operative material. In 32 cases kidney tumors were hyperechogeneous, in 13 cases- medium echogeneous, and in 8 cases--hypoechogeneous. The authors detected no relationship between a degree of vascularization of the tumor and its echogeneous type. By their results hypernephromas can have a different echographic picture which may be determined by tumor macromorphology (the presence of necrosis, cystic cavities, etc.). Sizes of kidney tumors by USI findings were 10-15% less than true tumor sizes, and the determination of tumor borders based on USI findings, was rather difficult. PMID- 2195761 TI - [Digital radiography (review of the literature)]. PMID- 2195760 TI - [Problems and perspectives of radiotherapy of non-tumor diseases]. AB - The experience of the world leading hospitals confirms the high efficacy and appropriateness of radiation therapy of nontumorous diseases. The authors consider the general principles of the organization of radiotherapeutic service, discuss reasons that have led to a decrease in the use of this method for therapy of nontumorous diseases in this country. They also emphasize the fact that radiation therapy must have its place among therapeutic modalities used for nontumorous diseases. PMID- 2195763 TI - [On the 100th anniversary of Ruvim Iakovlevich Gasul']. PMID- 2195762 TI - [Ultrasonic and x-ray computed tomography in the diagnosis of diseases of the organs of the abdominal cavity and the retroperitoneal space (review of the literature)]. PMID- 2195764 TI - [Treatment of epilepsy in adults]. PMID- 2195765 TI - [The main military hospital of the Yugoslav National Liberation Army during the war from 25 October 1944 to 31 May 1945]. PMID- 2195766 TI - [Magnetotherapy in cardiology (a review of the literature)]. PMID- 2195767 TI - [Delta hepatitis as a mixed infection]. AB - Radioimmunoassay of 247 patients revealed in their sera 8 cases of anti-delta agents. On the basis of testing of HBV infection markers the authors revealed three cases of coinfection and five cases of delta superinfection. A fatal case of fulminant hepatitis with development of acute liver dystrophy was observed in one patient with coinfection. In two other patients the course of the disease was severe but ended in recovery. Superinfection with delta agent resulted in a progression of the disease with early formation of chronic active hepatitis. This form chronic disease was characterized by a malignant course and proved resistant to immunosuppressive therapy. The clinical and biochemical signs of coinfection and delta superinfection are discussed. PMID- 2195768 TI - [The malignant degeneration of stomach ulcers (a review of the literature)]. PMID- 2195769 TI - [Delta hepatitis (a review of the literature)]. PMID- 2195770 TI - [Cigarette smoking: a main preventable cause of death. The main public health problem of our times]. AB - Cigarette smoking is one of the most important factors endangering the health and life of modern man. Unfortunately the statistics in recent years showed that Poland is now among the countries with the highest consumption of cigarettes in the world. According to the data reported in 1982 by the Polish Anti-tobacco Association our population consists in a great part of habitual smokers, since about 12 million people are smoking cigarettes (over 60% of men and 30% of women). Another diquieting fact is the continuous rise of the proportion of heavy smokers, who smoke over 20 cigarettes daily, which increases many times the health risk. PMID- 2195771 TI - [Silent ischemia]. AB - Silent ischaemia is the term which has appeared with the development of such diagnostic techniques as exercise test or Holter ECG monitoring. The term relates to depression of the ST-T segment in ECG despite absence of pain felt by the patient. Episodes of silent ischaemia occur in all clinical forms of coronary disease, are of prognostic importance and require treatment with monitoring of treatment effectiveness. The problem of pain absence in certain ischaemic episodes has not yet been elucidated. PMID- 2195772 TI - [Ethyl alcohol and alcoholism and the macrophage-monocyte system]. PMID- 2195773 TI - [Professor Tytus Chalubinski--symbol for the physician and citizen (on the centenary of his death)]. PMID- 2195775 TI - [Local complications of long term treatment with intravenous cytostatic agents- prevention and treatment]. AB - Methods are described of preventing of accidental extravenous injection of cytostatics and treatment of this complication. PMID- 2195774 TI - [Usefulness of beta-2-microglobulin determination in the differential diagnosis of infections in the upper and lower parts of the urinary tract]. AB - The purpose of the study was assessment of the usefulness of renal excretion of beta 2-microglobulin (B2M) in the differential diagnosis of infections situated in the upper and lower parts of the urinary tract. The study was carried out in 15 patients with infections of the upper part of the urinary tract (acute pyelonephritis), 10 patients with infections of the lower part of this tract (cystitis), and 50 healthy controls. In all studied subjects the B2M concentration was assessed in the serum and urine by radioimmunoassay (Pharmacia B2-micro RIO 100, Uppsala, Sweden). From the obtained data B2M clearance (CB2M) and tubular reabsorption of B2M (TRB2M) were calculated. In patients with upper urinary tract infections a statistically significantly greater urinary B2M excretion, significantly higher CB2M value, and significantly decreased TRB2M were found as compared to patients with lower urinary tract infections. The obtained data suggest presence of dysfunction of the proximal tubule in upper urinary tract infections and demonstrate the usefulness of beta 2 microglobulinuria assessment in the differential diagnosis of upper and lower urinary tract infections. PMID- 2195776 TI - [Symptoms, diagnosis and prognosis of multiple sclerosis in children]. PMID- 2195777 TI - [Renal diseases in patients with the acquired immunodeficiency syndrome]. AB - A survey is presented of the views and opinions in the literature on renal diseases in AIDS. Particular attention is paid to acute renal failure, glomerulonephritis, nephrotic syndrome and management of patients treated with dialyses and renal transplantation. PMID- 2195778 TI - [Hypermagnesemia in hemodialysis due to excessive concentration of the element in the dialysate]. AB - Seven patients with chronic renal failure are reported in whom hypermagnesemia developed due to incorrect composition of the dialysing fluid used for haemodialysis. On the basis of these cases and literature reports the authors discuss modern views on the use of magnesium compounds in patients with chronic renal failure. It is thought that in the management of hypermagnesemia a great role is played, besides calcium preparations, by haemodialysis and peritoneal dialysis. PMID- 2195779 TI - [Multiple sclerosis--biochemical-immunologic and therapeutic aspects]. PMID- 2195780 TI - Converting enzyme inhibitors and calcium antagonists in the long-term treatment of hypertension in chronic renal failure. AB - Hypertension contributes to the inexorable decline of renal function in patients with chronic renal impairment. Studies on the long-term use of converting enzyme inhibitors and calcium antagonists in the treatment of hypertension in patients with chronic renal failure are hereby reviewed. The data demonstrate that converting enzyme inhibitors are effective antihypertensives in diabetic nephropathy and other forms of chronic renal failure. Furthermore, the results suggest that long-term treatment with captopril may slow the progression of renal impairment in diabetic nephropathy, whereas the data are inconclusive for non diabetic nephropathies. A reduction of proteinuria or albuminuria was also observed in most trials during long-term converting enzyme inhibition. Treatment with calcium antagonists also led to effective blood pressure control in hypertensive patients with renal disease. However, the very limited data in humans suggest no consistent beneficial effect on kidney function or proteinuria. More controlled studies are necessary to determine the relative efficacy and safety of converting enzyme inhibitors and calcium antagonists in comparison with "standard antihypertensives" in long-term antihypertensive treatment of patients with various forms of chronic renal failure. PMID- 2195781 TI - [Karl Frederik Wenkebach (1864-1940) and the establishment of the Institute for the History of Medicine in the historical building of the Joseph Academy in Vienna: 1990 as a double anniversary year]. AB - The Vienna Chair for the History of Medicine was founded in 1848, and the History of Medicine Department has been in existence since 1907-1913. Karel Frederik Wenckebach, the famous specialist in internal medicine, who died exactly 50 years ago, was instrumental in creating a permanent domicile for this institute in 1920, in the historical building of the Vienna Military Medical Academy (Joseph's Academy). PMID- 2195782 TI - [Milestones in heart surgery]. PMID- 2195783 TI - [Discussion forum on medical ethics. A8. How can ethics be made practical? 3 philosophical positions]. AB - Ethics as a theory of morality is expected to find a way into practical use. A short historical overview from Aristotle's hermeneutic ethic and the axiomatic position of Kant and Fichte leads to a modern "analysis of possibility" which shows up a new approach solving the practical dimensions of ethics. PMID- 2195785 TI - [The significance of Giardia lamblia for water hygiene]. AB - This paper gives a literature review about Giardia lamblia, an unicellular infectious agent, which is responsible for parasitic intestine-diseases. Morphologically, life-cycle, occurrence and caused symptoms of illnesses are described. The content of this publication is the question about the meaning of the importance of the pathogenic agent for water-borne epidemics. During the past 15-20 years the number of cases of water-transmitted giardiasis has increased enormously, especially in the USA, but in other countries, too. Modes of transmission of drinking-water supplied with surface-water are the origins as a rule. The set of problems becomes more interesting, because in Hungary cysts of Giardia lamblia in drinking-water were isolated recently. In this context it is to refer to the not unimportant number of unspecific diarrhoea with obscure origin in general. That's why it is necessary to value Giardia lamblia under the conditions of using surface-water for drinking-water as a potential water hygienic factor of risk. PMID- 2195784 TI - Hypoglycemia induced by excessive rebound secretion of insulin after removal of pheochromocytoma. AB - During an 8-year-period from 1981, a total of 6 of 45 patients with pheochromocytoma developed severe hypoglycemia (plasma glucose, 12-50 mg/dl) 2-4 1/2 hours after removal of the tumor. In order to elucidate the pathogenesis of the hypoglycemic attack, the levels of plasma immunoreactive insulin (IRI) and glucose were sequentially measured at surgery in 10 patients with pheochromocytoma, from the beginning of the operation until usually 5 hours after tumor resection. The same examinations were carried out in 4 patients with primary aldosteronism and 1 patient with Cushing's syndrome as controls. The highest plasma IRI levels observed in the 2 patients with postexcisional hypoglycemia were 174 and 2,081 microU/ml and those in the 8 patients without hypoglycemia were 13-222 microU/ml (mean, 77), but they were only 14-33 microU/ml (mean, 22) in the 5 control patients. The mean of the highest plasma IRI/glucose ratios in the immediate postoperative phase was 1.37 +/- 0.87 in the 10 patients with pheochromocytoma but only 0.16 +/- 0.04 in the 5 control patients (p less than 0.01). Review of the clinical data in our series disclosed that patients with higher levels of preoperative urinary epinephrine excretion and those with either diabetes mellitus or impaired glucose tolerance tended to develop postoperative hypoglycemia. These observations suggest that endogenous insulin secretion is suppressed by increase plasma catecholamines, and that excessive rebound secretion of insulin after removal of a pheochromocytoma is a rather common phenomenon. Intravenous infusion of glucose is necessary and plasma glucose levels should be monitored after resection of a pheochromocytoma. PMID- 2195786 TI - [Ultrasound examination of the skin in preoperative diagnosis]. PMID- 2195787 TI - [Psychology of youth in adolescence]. AB - Adolescence is a phase of human development characterized by major psychophysiological transformations and a high vulnerability and/or potential for disturbance. It can be divided into 5 subphases. For the assessment of the psychopathology and the resources it is important not only to evaluate the individual structure and psychodynamics but also to include the interpersonal relationships (family, peer group) in the diagnostic process. PMID- 2195788 TI - [Andrologic problems in adolescence]. AB - No precise distinction is usually made now between puberty and adolescence. Therefore, we describe the physiology and pathology of both phases with their characteristic clinical features, hormonal changes, and therapeutic consequences. In addition, we refer to the typical problems of this age group, the psychic and somatic variants of the norm; special regard is paid to puberal gynecomastia and obesity. PMID- 2195789 TI - [Skin changes in drug-dependent patients]. AB - In parenteral drug abuse, cutaneous manifestations are very common. A variety of skin lesions are indicators of a possible drug addiction: obliteration of peripheral veins and hyperpigmentation of the overlying skin, punched-out scars due to subcutaneous injection, persistent edema following thrombophlebitis, and excoriations due to heroin pruritus. Infectious and non-infectious complications may be accompanied by typical skin alterations, such as ecthyma in sepsis caused by Pseudomonas aeruginosa, multiple ulcers due to embolic infarct, or hypersensitivity reactions mediated by an immunological process. A variety of serious complications may develop at the injection sites: abscesses, gangrene, necrosis, or necrotizing fasciitis. These examples show that the dermatologist is in many ways involved in the care for addicted patients. In addition, these patients frequently suffer from sexually transmitted diseases or blood-borne infections; HIV-infection is rapidly spreading in this group. We now face new problems of differential diagnosis, especially since constitutional symptoms of HIV-infection may mimic symptoms of drug abuse and vice versa. Moreover, immunological alterations similar to those in HIV patients may even occur in drug addicts who are not infected with the virus. PMID- 2195790 TI - [Microbial ecosystems of the skin in antimicrobial therapy]. AB - Healthy human skin provides wet, dry, and sebaceous habitats for well-adapted microbes living in a community and occupying three-dimensional spaces of the skin. These resident microbes of the skin are reduced either intentionally or unintentionally under systemic or topical antimicrobial therapy, e.g. in acne or tinea versicolor. As a result, quantitative or qualitative alterations of the microbial communities might ensue, including the selection of multiresistent variants in a habitat or a total change of the microbial community followed by the so-called gram-negative folliculitis. Skin disinfectants are antimicrobially effective within 30 to 60 seconds. Their long-term efficacy varies according to the specific substance. Moreover, the antimicrobial efficacy of skin disinfectants may vary to a considerable degree in the individual habitats of the human skin. PMID- 2195791 TI - [A combination of psoriasis vulgaris and nevus cell nevus--clinical, histopathologic and histochemical findings]. AB - In a study on 76 patients suffering from psoriasis, we found melanocytic nevi (MCN) within psoriatic lesions in 7%, and in perilesional areas of about 2 cm in 13% of the patients. Under magnification (operating microscope), we failed to detect any signs of psoriasis in both the epidermis covering the MCN and the adjacent epidermis. Histopathologically, 6 out of 7 MCN examined did not show any psoriatic alterations of the epidermis, and in all the 7 cases, the adjacent epidermis was free of psoriasis. Using unfixed frozen sections in histochemistry, we studied the lectin binding of FITC-labeled ConA and UEA I in 5 MCN. The epidermal reaction was comparable to that of psoriatic lesions. In contrast to psoriatic lesions, there was no staining of the spinous layer with a polyclonal antiserum against calmodulin, but only the staining of basal cells as in non lesional psoriasis. We discuss possible 'protective' factors against psoriasis. PMID- 2195792 TI - A resin retained interim fixed partial denture. PMID- 2195794 TI - [Ideas and problems of medical anthropology]. PMID- 2195793 TI - [The Great French Revolution and medicine]. PMID- 2195795 TI - [Histiocytosis X. Letterer-Siwe disease]. PMID- 2195796 TI - [The functional characteristics of the interaction of lymphokine-producing lymphocytes with granulocytes of the peripheral blood and skin in dermatosis patients]. AB - PHA-induced mononuclear production of lymphokines altering leukocyte migration was studied in patients with psoriasis, mycosis, and scabies. The findings evidence that T-cells synthesize leukocyte migration inhibition factor (LMIF) in mycosis and scabies, whereas in psoriasis they produce both LMIF and leukocyte migration stimulation factor (LMSF). Blood leukocytes of mycosis and scabies patients were more sensitive to LMIF than the cells of psoriasis patients. The 'skin fenestra' cells (granulocytes) of these patients were functionally active only in respect of LMIF, even when mononuclears synthesized LMSF, this evidencing the participation of skin leukocytes of psoriasis patients in blockage of the functional activity of LMSF-producing immunocompetent cells. PMID- 2195797 TI - [Recurrences of gonorrhea in men (the characteristics of the course and treatment)]. AB - The examination has involved 218 patients. The incidence of relapses in acute and subacute gonorrhea has made up 6.3%, 5.2% in chronic and 4.5% in complicated condition. Recurrences were observed in 5.3 days on an average after therapy of new gonorrhea cases and in 8.8 days after treatment of chronic disease. Mixed urogenital infection was recorded in 37.8% of cases; in gonorrhea eventuating in clinical cure it was observed in 24% of cases. Relapses developed in 50.2% of patients after antibiotic therapy and in 49.8% after combined treatment. A single relapse occurred in 85.6% of patients; two and more relapses in 14.4%. The disease recurred after penicillin therapy in 6.5% after aminoglycosides in 6.9%, and after tetracyclin treatment in 4.2% of cases. Therapy with proteolytic enzymes (chymotrypsin, trypsin 5 mg i.m. twice a day) combined with antibiotics resulted in etiological cure in 99.3% of patients, the incidence of postgonorrheal symptoms reduced and made up 6.8% (in the patients not administered protease this share made up 19.2%), and the length of inpatient treatment shortened by 8-14.6 days. PMID- 2195798 TI - [Endogenous regulatory oligopeptides: their structure, functions and localization]. AB - A number of problems connected with the study of several hundreds of known endogenous peptide molecules have been considered on the basis of data obtained from EROP-Moscow database. A large number of peptide structures can be reduced to a relatively small number of peptide families formed on the basis of homology of amino acid sequence. The ability of most peptides to participate in different regulatory systems of an organism has been demonstrated and the physical and chemical basis for specificity and ambiguity has been discussed. Most problems of structure, function, and localization of endogenous regulatory peptides are similar both in higher and in lower organisms. PMID- 2195799 TI - [Experiences with ureterosigmoidostomy]. AB - It is reported on the experience with ureterosigmoideostomy in 59 patients. Because of the good long-term results with a maximum follow-up time of 20 years especially in patients suffering from benign congenital anomaly the authors emphasize the current value of ureterosigmoideostomy especially in the treatment of bladder extrophy and aplasy of the urethra and urethral sphincter. In 3 female patients some years after operation a healthy child was born on the natural way. PMID- 2195800 TI - [A clinical trial of pefloxacin (Abaktal) in the treatment of acute pyelonephritis]. AB - The therapeutic effect of Pefloxacin in the treatment of acute pyelonephritis was examined in a randomized clinical trial. The patients in the control group have been treated by gentamycin. With a success rate of 80% in the treatment of acute pyelonephritis caused by various bacteria (E. coli, Pseudomonas, Klebsiella, Staphylococcus aureus, Proteus mirab.), a side frequency of side effects and a good compliance Pefloxacin is recommended as an effective antimicrobiell drug. PMID- 2195801 TI - [Transplantation of the kidneys of donors with cancer--personal experiences and review of the literature]. AB - From 1980 to 1988 more than 1,549 organ donors were harvested, 125 of them (8%) died from cancer--116 brain tumors and 9 donors with extracerebral cancer. In 3 donors suffering from extracerebral cancer 5 kidneys were transplanted. All transplants functioned well without tumor signs up to 21 months after grafting. However, because of tumor recurrence in nearly 50% of the cases described in the literature generally organs from donors suffering from extracerebral cancer should not transplanted if possible. PMID- 2195802 TI - [Systematic aspects of the loop syndrome following stomach resection with reference to the Roux modification]. AB - The contradictions implied in any effort to differentiate from each other postoperative loop syndromes following partial gastrectomy were found to call for systematisation. Reference is made in this paper to syndromes of afferent and efferent loops. The authors present their own modification developed to prevent the Roux-Y syndrome. PMID- 2195803 TI - [Differential ultrasound diagnosis of the healthy, inflamed and diseased gallbladder]. AB - Sonography is helpful in detection of gallstones and can also provide information on pathological changes of the gallbladder. The diagnosis of changes of gallbladder walls is difficult without clinical symptoms. "Pharmakocholocystosonography" can provide information by diseases of gallbladder. It proves that the "asymptomatic" gallstone is one of symptoms of this disease. The sonography is helpful too in the diagnosis of the acute cholecystitis if the clinical symptoms are respected. PMID- 2195804 TI - [Almost 40 years' survival with the "Biebl stomach"]. PMID- 2195805 TI - [Isolated gallbladder hematoma and covered perforation following blunt abdominal trauma]. PMID- 2195806 TI - [Therapeutic strategy and prognosis of malignant struma]. AB - The systematic application of combined treatment modalities including surgery, radiotherapy and suppressive hormone administration is based on a biologically relevant histomorphologic tumour classification. Although the principle of an aggressive therapeutic approach is still valid meantime a limited radicality has proven equally successful for selected early cases. On the other hand an even extended radical strategy is followed by repeated surgery for local recurrencies and metastatic lesions. PMID- 2195807 TI - [How reliable is ultrasound fetometry?]. PMID- 2195808 TI - [Gastrointestinal side effects of cytostatic treatment of gynecologic neoplasms]. AB - Gastrointestinal complaints are the most frequent side effects of antineoplastic chemotherapy behind the bonemarrow depressions. Nearly all cytostatic drugs, favourably used treating gynaecological malignant tumours, show a high complication rats on the part of the digestive organs. Primary an secondary damages can be so serious that the continuation of an effective tumour therapy becomes impossible. Whereas mucous excitement and motility disturbances are caused by local toxicity of cytostatic drugs, on the other hand central and psychogenic factors are of essential importance concerning nausea and vomiting. Therefore all these side effects could not be treated effective antiemetics alone. Only by an ingenious combination of medical treatment, psychological guidance and appropriate nutrition complaints can be relieved so far that the patients quality of life is interfered as less as possible and that a sufficient compliance may be reached. PMID- 2195809 TI - [The transformation of legionellae by plasmid DNA]. AB - For the first time the possibility of the genetic transformation of L. pneumophila and L. bozemanii strains with the use of purified DNA of plasmids pUC19, pUC4K, pSC101 and RSF1010-pBR322 was shown. The frequency of transformation varied from 5.2 x 10(-6) to 5.8 x 10(-7), depending on the strain used in the experiment and plasmid DNA. In some of the transformants obtained in this investigation plasmid DNA whose molecular weight was similar to that of the plasmid DNA used for transformation was detected. The relatively stable preservation of plasmids pSC101 and RSF1010 in Legionella strains and the loss of plasmids pUC19, pUC4K and pBR322 in 80% of transformants during storage were shown. PMID- 2195810 TI - [Microbiologic and histomorphologic characteristics of experimental Mycoplasma pneumococcus infection]. AB - The specific features of the development of Mycoplasma pneumoniae and Streptococcus pneumoniae infections in mice have been studied in cases of mixed and monoinfections. As shown in this study, mixed infection is characterized by the mutual inhibition of the proliferation of both pneumococci and mycoplasmae in the lungs, the liver and the spleen of the animals, while the associative interaction of these infective agents in isolated mouse lung tissue is characterized by the inhibition of pneumococcal proliferation only. In mixed infection the early activation of cells of the immunocompetent system is observed, which is accompanied by the development of mainly cell-mediated immune processes manifested as delayed hypersensitivity with the late formation of fibrillogenesis. During the development of mixed mycoplasmal-pneumococcal infection the histopathology of mycoplasmal infection prevails, which is probably due to the early formation of delayed hypersensitivity to M. pneumoniae in the animals. PMID- 2195811 TI - [The importance of Shigella boydii in shigellosis morbidity in the USSR]. AB - The etiological role of S. boydii in Shigella infections registered at different territories of the USSR in 1986-1987 was analyzed. As established by this analysis, S. boydii infection occurred mainly at the territories with unsatisfactory water supply of the population; from these territories the infection spread to ther territories of the USSR. The dominating serovars causing S. boydii dysentery, as well as Shigella infections, at different territories of the USSR was shown to be identical, which was indicative of the fact that the immunological factor had no influence on the etiological structure of Shigella infections, determined by the activity of the main routes of the transfer of infection. On the whole, S. boydii serovars 2, 4 and 1 were found to prevail in the USSR. PMID- 2195812 TI - [Control of the mutagenicity of a new immunomodulator]. AB - New immunostimulator STP, peptide isolated from the cultivation medium of Streptococcus species producer strain TOM-1606 by chromatographic purification, was controlled for mutagenicity. The preparation, introduced into mice in doses of 6.7 X 10(2) - 6.7 X 10(4) micrograms/kg, i.e. exceeding the stimulating dose 1000-fold, did not induce the appearance of micronuclei in polychromatophilic erythrocytes of the marrow, the fixation of the material being made 24, 48 and 72 hours after the injection. In Ames' test on Salmonella typhimurium strains TA 98 and TA 100 neither native STP, nor STP activated with the microsomal fraction of rat liver enzymes did not increase the frequency of reversions to histidine independence. The absence of mutagenic properties in STP was demonstrated by the parallel pronounced genotoxic action of a number of known mutagens used as positive controls. PMID- 2195813 TI - [The capacity to produce cholera exotoxin in natural strains of Vibrio cholerae]. AB - The study of 27 V. cholerae strains, isolated from cholera patients and found to be hemolytically inactive, with a view to establish their capacity for the production of cholera toxin has revealed that 4 strains (V. cholerae cholerae Dacca 35, V. cholerae cholerae Dacca 3, V. cholerae cholerae B1307, V. cholerae cholerae J89) produce this protein. The quantitative determination of enterotoxin has been made with the use of GM1 ELISA technique. Strain Dacca 35 has been found to be highly toxigenic and, as regards the amount of exotoxin it produces, no different from V. cholerae cholerae strain 569B, a well-known producer of cholera toxin. In strain Dacca 35 correlation between the capacity of the cells for toxin production and the morphology of colonies has been established. The study has revealed that the chromosome of strain Dacca 35 contains two copies of gene vctAB responsible for the synthesis of cholera toxin. PMID- 2195814 TI - [Epidemiologic surveillance of obligate transmissible rickettsiosis with natural foci]. PMID- 2195815 TI - [The typing of the causative agents of infectious diseases today]. PMID- 2195816 TI - Prophylactic treatment with an aerosolized corticosteroid liposome in a porcine model of early ARDS induced by endotoxaemia. AB - The effects of prophylactic treatment with an aerosolized corticosteroid liposome (CSL) in high dose were evaluated in a porcine model of early Adult Respiratory Distress Syndrome (ARDS) induced by endotoxaemia. Intermittent positive pressure ventilated (IPPV) pigs under chlormethiazole anaesthesia were infused with E. coli endotoxin (18 micrograms.kg-1.h-1) over 4 h. Eight animals served as controls and were pretreated with aerosolized placebo liposomes, either 15 min or 2 h, before start of the endotoxin infusion. Eight animals were pretreated with CSL in aerosolized form 15 min before start of endotoxin, and eight animals were pretreated 2 h before start of endotoxin. Pretreatment with CSL, both 15 min and 2 h before endotoxin, modified and partly counteracted the late endotoxin-induced impairment in expiratory resistance (EXPres), dynamic compliance (Cdyn) and mean pulmonary artery pressure (MPAP). The administration of CSL did not seem to have a restrictive influence on the endogenous cortisol production estimated by repeated measurements of serum cortisol levels. These results indicate that CSL, administered prophylactically in an aerosolized form to the lung, might be valuable as a modulator without systemic side effects in regard to some of the endotoxin-induced pulmonary impairments seen in this experimental model of early ARDS. PMID- 2195817 TI - Popliteal valve incompetence and postoperative deep vein thrombosis. AB - In 79 patients undergoing hip or knee replacement surgery the preoperative condition of the popliteal vein valves was assessed by Doppler ultrasonography. Presence of postoperative deep vein thrombosis was determined by bilateral ascending phlebography seven to ten days after surgery. Antithrombotic prophylaxis consisted solely of TED stockings and early mobilization. The overall incidence of deep vein thrombosis was 20%. All thrombi were calf vein thrombi. One of these thrombi extended into the popliteal region and two into the femoral region. The incidence of deep vein thrombosis in patients with preoperative popliteal vein reflux when compared with patients with a normal popliteal valvular function was 55-15% (p less than 0.01). The incidence of deep vein thrombosis was also significantly lower in patients operated under epidural anaesthesia compared with patients under general anaesthesia. It is concluded that valvular incompetence of the popliteal vein predisposes to postoperative deep vein thrombosis. PMID- 2195818 TI - Radiotherapy additional to surgery in the management of primary rectal carcinoma. PMID- 2195819 TI - Optimal collaboration between the vascular diagnostic laboratory (VDL) and the surgeon. PMID- 2195820 TI - Management of late failures of femoro-popliteal and femoro-distal bypasses. PMID- 2195821 TI - Can prosthetic graft infection be avoided? If not, how do we treat it? AB - Most arterial prosthetic graft infections can be prevented although a few will inevitably still occur. Maintaining a high index of suspicion for graft infection permits prompt diagnosis which provides the opportunity for early surgical management and improved potential for a good result. Aortic graft infection is best managed with extra-anatomical prosthetic bypass through clean tissue followed by graft excision. Results with this surgical approach are improving. Recently, authors advocating in situ grafting for graft enteric fistula as well as others recommending nonresectional therapy for localized prosthetic graft infections, have obtained encouraging results comparable to the best series of more standard excisional therapy. Because prosthetic graft infection remains a difficult surgical problem, any potentially useful management innovations warrant serious consideration and analysis with extended follow-up. PMID- 2195823 TI - Optimal methods to assess the deep venous system in the lower limb. PMID- 2195822 TI - Diagnosis, treatment and prevention of aorto-enteric fistulas. PMID- 2195824 TI - Why do so few surgeons perform reconstructive venous surgery? Reconstruction for deep venous insufficiency in the 1990's. PMID- 2195825 TI - Does thrombectomy still have a place in the treatment of acute deep venous thrombosis? PMID- 2195826 TI - How to predict which patient with carotid atherosclerosis is "high risk". PMID- 2195827 TI - Optimal reconstruction of the renal arteries. PMID- 2195828 TI - Chronic intestinal ischaemia. PMID- 2195829 TI - Vascular grafts in the 1990s: lessons from the past. PMID- 2195830 TI - The best alternative to reduce thrombogenicity of small diameter grafts. PMID- 2195831 TI - The practical consequences of research in arteriosclerosis. AB - Despite the impressive volume of work that has been undertaken, the successful medical therapy of arteriosclerosis continues to elude us--preventive measures and surgical treatment of its complications persist as the primary modalities of treatment. While research into the fundamental pathophysiology surrounding arteriosclerosis is not complete and our understanding is plagued by the current plethora of confusing and contradictory reports, the cellular mechanisms underlying this process are gradually being clarified. As yet, this basic research has had limited impact for vascular surgical patients, who have benefited more as a result of epidemiological studies. For instance, we are more diligent in looking for occult disease, less ready to operate on obvious lesions, and more persuasive in our attempts to alter the patient's lifestyle- particularly smoking habits. PMID- 2195832 TI - Adjuvant medical therapy to improve patency rate following reconstruction for atherosclerosis obliterans (ASO). PMID- 2195833 TI - Extra-anatomic bypass for treatment of leg ischemia. PMID- 2195834 TI - Should screening for abdominal aortic aneurysms be advocated? PMID- 2195835 TI - [Epithelioma of the maxillary sinus with inguinal metastases. Case report and literature review of multiple tumors in gastroenterology]. AB - Squamous cell carcinoma of the maxillary sinus with inguinal metastases. Report of a case and review of the literature on multiple primaries and gastrointestinal malignancies. The authors report a case of squamous cell carcinoma of the maxillary sinus associated with an anaplastic carcinoma of the caecum with inguinal metastases. The authors review the literature about tumours of the gastrointestinal tract occurring simultaneously with primary tumours of other organs. PMID- 2195836 TI - Primary malignant lymphoma of the liver. Report of two cases and review of the literature. AB - We present two cases of primary malignant lymphoma of the liver, a very unusual localization of primary malignant lymphoma since only 31 similar cases were reported in the literature. The main symptoms included: hepatomegaly, fever, slight cholestasis and non specific alteration of the liver appearance on ultrasonography or computed tomodensitometry examination. Diagnosis was established in both cases by histopathological demonstration of infiltration by large lymphoid cells. Immunophenotyping in one case confirmed a B cell phenotype. Primary malignant lymphomas of the liver are high-grade malignant large-cell tumours and the immunophenotype, when known, is of the B type. The prognosis of these tumours is not well known due to their extreme rarity. They appear to be highly chemosensitive and cure may be obtained in the long-term in some cases. These data justify careful histological assessment in all cases of hepatomegaly of a tumoral nature. PMID- 2195837 TI - Ciclosporin administration during pregnancy induces ultrastructural changes on pancreatic beta-cells of newborn rats. AB - Ciclosporin (CS) is an immunosuppressive agent used in the prevention of graft rejections and in the management of type 1 diabetes. However, the drug is not without side effects. The aim of this study was to evaluate eventual cytotoxic phenomena in the pancreas of newborn rats whose mothers had been treated with therapeutic doses of CS. For this purpose, 25 female Wistar rats were used, 20 of which were subjected to daily injections of 10 mg/kg BW/day i.p. of CS dissolved in Intralipid, administered during the whole gestational period. The results obtained indicated that CS did not arrest fetal development, even though the number of newborns per mother was reduced when compared to controls. Moreover, mothers and newborn rats were subjected to vacuolation of kidney proximal tubular cells and of the insulin-secreting pancreatic beta-cells. This alteration was more evident in the islet beta-cells of newborn rats. Therefore, CS is not only toxic to the mothers' endocrine beta-cells but also to those of any eventual offspring. PMID- 2195838 TI - Morphology of day 7 bovine demi-embryos during in vitro reorganization. AB - Non-surgically collected day 7 bovine embryos were microsurgically cleaved and reinserted into surrogate zonae pellucidae. The demi-embryos were fixed immediately after splitting and at various intervals of in vitro incubation at 35 degrees C in modified Dulbecco's medium. At the light-microscopical level, the demi-embryos were found to have restored their prebisection morphology within 30 min after splitting. The electron microscopy confirmed these findings, by the presence of mitosis, cell polarization, neoformation and reaggregation of mitochondria, increased pinocytosis and cell-to-cell contact between trophoblastic and/or inner cell mass cells. The present observations therefore suggest that day 7 bovine demi-embryos intended for transfer should be cultured for 30 min before being morphologically evaluated. PMID- 2195839 TI - Proximo-occlusal composite restorations in primary molars: marginal adaptation, bacterial penetration, and pulpal reactions. AB - Marginal adaptation and bacterial penetration were studied in 32 primary molars filled with composite resin in shallow class II cavities. The restorations had served in the mouth for 3 years (mean, 3 years and 4 months; range, 8 months to 6 years and 4 months). Ground sections of the retrieved teeth were evaluated with polarized light microscopy and demineralized sections with light microscopy. Clinically excellent restorations, free from bacteria, were found in 25%. Gaps were recorded in 42%, under- or over-contouring and porosities in 95%, caries in the cervical area in 58%. Bacteria were observed subjacent to the fillings in 75% and in the dentin tubules in 61%. Pupal necrosis was found in 7 of 16 teeth. Marginal discoloration, visible crevice, or color mismatch was associated with marginal defects, bacterial leakage, and pulpal reactions. PMID- 2195840 TI - Effect of TiF4 solutions on bacterial growth in vitro and on tooth surfaces. AB - The purpose of this study was to assess the antimicrobial effect of TiF4 as compared with equimolar solutions of NaF, APF, and SnF2 and to evaluate the effect, if any, on bacterial growth on topically treated tooth surfaces. In an in vitro study, paper discs impregnated with 20 microliters of equimolar solutions of SnF2, NaF, APF, and TiF4 were placed on blood agar plates seeded with Streptococcus mutans and Bacteroides gingivalis. Sterile saline was used as control. Similar growth inhibition zones were found for all fluorides. In the second part of the study six volunteers carried intraoral appliances containing enamel and root surface specimens treated with 1% TiF4 and untreated specimens for 18 h. Scanning electron microscopic examination of the experimental tooth surfaces showed great variation in bacterial growth between subjects, but no systematic difference between fluoride-treated and untreated specimens. Bacteria from test and control specimens were grown under aerobic and anaerobic conditions on blood agar and on mitis salivarius agar. Colony-forming unit counts showed great interindividual variations, but no differences could be observed between treated and untreated enamel or root surfaces. Thus, the hypothesis that the presence of a Ti-rich coating may influence bacterial colonization on TiF4 treated tooth surfaces could not be substantiated. PMID- 2195842 TI - Orthopaedic glossary. PMID- 2195841 TI - An estimation of dental treatment needs in two groups of refugees in Sweden. AB - The aim of this study was to estimate dental treatment need in groups of Chilean and Polish refugees in Sweden. Of the Nordic countries, Sweden accepts the greatest number of refugees. An average of 5000 refugees arrived annually in 1981 85, increasing to 15,000 during 1986-87. Refugees and their families now comprise 93% of non-Nordic immigration. In 1981-83 a sample of 193 Chilean and 92 Polish refugees in the county of Stockholm was selected for this study. Dental treatment needs were calculated in accordance with CPITN and the working study of Swedish dentistry, which formed the basis for the Swedish scale of dental fees for the National Dental Insurance Scheme. The estimated mean treatment time (+/- SD) in the Chilean sample was 6.9 +/- 2.3 h and in the Polish group 8.4 +/- 3.0; in comparison with estimated treatment needs in a Swedish material, both would be classified as extreme risk groups. There was no correlation between the number of months in Sweden and the estimated treatment needs. The results indicate a cumulative, unmet need for dental care in these groups. Barriers to ensuring adequate health care for immigrants persist; special outreach programmes, conducted by dental health personnel, may be an effective means of introducing immigrants to the Swedish dental care system. PMID- 2195843 TI - Bone density changes in osteoporosis-prone women exposed to pulsed electromagnetic fields (PEMFs). AB - To determine the effect of a 72 Hz pulsating electromagnetic field (PEMF) on bone density of the radii of osteoporosis-prone women, the nondominant forearms of 20 subjects were exposed to PEMF 10 h daily for a period of 12 weeks. Bone density before, during, and after the exposure period was determined by use of a Norland Cameron bone mineral analyzer. Bone mineral densities of the treated radii measured by single-photon densitometry increased significantly in the immediate area of the field during the exposure period and decreased during the following 36 weeks. A similar but weaker response occurred in the opposite arm, suggesting a "cross-talk" effect on the nontreated radii, from either possible arm proximity during sleep or very weak general field effects. The data suggest that properly applied PEMFs, if scaled for whole-body use, may have clinical application in the prevention and treatment of osteoporosis. PMID- 2195844 TI - Bone mineral content in hypothyroid male patients with hormone replacement: a 3 year study. AB - Several studies have reported that short-term thyroid replacement to the euthyroid state in hypothyroid patients produces loss of both cortical and trabecular bone. However, long-term follow-up studies on this subject have not been reported. We conducted a 3 year follow-up study on 35 white male patients, including 24 patients (group 1 and 2) with hypothyroidism receiving thyroid hormone replacement to the euthyroid state and 11 patients (groups 3 and 4) with Graves' disease. The bone mineral content of the distal radius was determined by single-photon absorption techniques with an iodine 125 source. It was found that there was no statistically significant difference in bone mineral content by year for any group, indicating no evidence of significant loss of cortical bone mineral by thyroid hormone replacement to the euthyroid state in hypothyroid patients. PMID- 2195845 TI - Treatment of Paget's disease of bone with aminohydroxybutylidene bisphosphonate. AB - This study examined the effects of aminohydroxybutylidene bisphosphonate in 30 patients with Paget's disease of bone, administered as an intravenous infusion for 5 consecutive days. Treatment (5 mg IV daily) induced marked suppression of biochemical indices of disease activity. Urinary excretion of hydroxyproline fell to 50% of pretreatment values within 2 weeks and was followed by a similar, but later, decline in the serum activity of alkaline phosphatase. Disease activity remained suppressed throughout the 6 months of observation, and only 1 patients showed biochemical signs of an early relapse. Symptomatic improvement was noted in 27 of the 30 patients. Bone biopsies, undertaken in 10 patients, indicated no adverse effects on mineralization. Transient falls were noted in the total white cell count, particularly the lymphocyte and neutrophil fractions, and were associated with short-lived fever in 3 patients. We conclude that short courses of intravenous AHButBP provide a promising treatment for active Paget's disease of bone. PMID- 2195846 TI - [Seasonal nature of birth of schizophrenic patients]. AB - The author makes a bibliographical review of the studies on the seasonal nature of births of schizophrenic patients. These studies show the greatest rate of births to be in the winter months and at the beginning of spring. It can be deduced that the seasonal nature of births of schizophrenic patients may represent an important support for the hypothesis of the viral etiology of schizophrenia. PMID- 2195847 TI - [Anxiety disorders. Current rereading of the book "Vital anguish" by Prof. J.L. Lopez Ibor, 1950]. AB - Anxiety disorders are studied following the criteria established by Prof. J. J. Lopez Ibor in his book "La Angustia Vital" (The Vital Anxiety), 1950. D.S.M. III is criticized by saying that it has substituted psychopathology with a pseudo scientific operativeness. PMID- 2195848 TI - Axonal regeneration in the mammalian central nervous system. A critique of hypotheses. PMID- 2195849 TI - Lambda repressor: a model system for understanding protein-DNA interactions and protein stability. PMID- 2195850 TI - Proteins of iron storage and transport. PMID- 2195851 TI - Sickle cell hemoglobin polymerization. PMID- 2195852 TI - New trends in the management of peritonsillar abscess. AB - Peritonsillar abscess is the most common complication of acute tonsillitis. Signs and symptoms include fever, unilateral sore throat, odynophagia and trismus. Optimal management consists of antibiotic therapy and drainage of the abscess. Controversy exists about the drainage procedure, which includes needle aspiration, incision and drainage, or acute tonsillectomy. Data indicate that outpatient needle aspiration, antibiotics and pain medication are effective treatment in 85 to 90 percent of patients with uncomplicated peritonsillar abscesses. PMID- 2195853 TI - Meckel's diverticulum. AB - Meckel's diverticulum, a relatively common congenital anomaly of the gastrointestinal tract, is present in approximately 2 percent of the population. When symptoms develop, they are usually the result of inflammation, hemorrhage or obstruction. Diagnosis is made by maintaining a high index of suspicion, carefully reviewing data from the history and physical examination, and performing a radionuclide scan. Surgical removal is usually indicated when symptoms occur. An asymptomatic Meckel's diverticulum that is discovered incidentally at surgery should usually be removed unless contraindications exist. PMID- 2195854 TI - Pharmacologic management of the symptoms of dementia. AB - Many patients with dementia have symptoms of depression and agitation in addition to the underlying cognitive impairment. These symptoms can be management problems for both the physician and the caregiver. In many cases, however, pharmacologic intervention is helpful. Even in dementia, depressive symptoms usually respond to antidepressant therapy. Neuroleptic medications are the drugs most commonly used to manage behavioral symptoms, such as agitation, suspiciousness, emotional lability, hostility and sleeplessness. A few studies have shown that ergoloid mesylates (Hydergine) can modestly improve cognitive function. Some experimental drugs also show promise in partially reversing the symptoms of intellectual decline. PMID- 2195855 TI - Counseling to prevent household and environmental injuries. U.S. Preventive Services Task Force. AB - RECOMMENDATION: Patients who use alcohol or other drugs should be warned against engaging in potentially dangerous activities while intoxicated. It may also be clinically prudent to provide counseling on other measures to reduce the risk of unintentional household or environmental injuries from falls, drownings, fires or burns, poisoning and firearms. PMID- 2195856 TI - Ankylosing spondylitis. AB - Associated with the presence of HLA-B27 antigen, this inflammatory disorder of unknown etiology predominantly affects young adult men. Most patients present with low back pain and stiffness. Radiographs may show erosions, sclerosis and ankylosis in the pelvis and in the discovertebral, apophyseal, costovertebral and atlantoaxial joints. Hips and shoulders are the peripheral joints most commonly affected. Although most of the axial and appendicular skeleton may be involved, bilateral and symmetric sacroiliac involvement is the hallmark of ankylosing spondylitis. PMID- 2195857 TI - Solar-induced epidermal tumors in the elderly. AB - Solar lentigo, actinic keratosis and Bowen's disease are common, solar-induced epidermal tumors in the elderly. Management of these lesions depends on the correct diagnosis, which may require biopsy. Treatment of solar lentigo includes cryosurgery followed by topical tretinoin and topical hydroquinone. Actinic keratosis may be treated with cryosurgery, topical 5-fluorouracil, topical tretinoin and, rarely, oral isotretinoin. Bowen's disease requires excision, cryosurgery, electrodesiccation with curettage, or chemosurgery; close follow-up examination is necessary, regardless of the type of treatment. Use of sunscreen products should be stressed as an important preventive measure for all three conditions. PMID- 2195858 TI - Pheochromocytoma. AB - Pheochromocytoma is a rare, potentially lethal cause of hypertension that is surgically reversible. Diagnosis may be difficult, because catecholamine release is often intermittent and the location of the lesion is variable. Management consists of blocking alpha-adrenergic stimulation preoperatively. This controls hypertension both before and during surgery. It also allows expansion of the intravascular volume, preventing postsurgical hypotension. Associated arrhythmias must also be controlled. After surgery, routine evaluation for tumor recurrence is essential. PMID- 2195859 TI - Magnesium replacement therapy. AB - Magnesium is involved as a cofactor in many vital enzymatic reactions. It is also important in the maintenance of membrane electric potential. Diagnosis of magnesium disturbances must often be based on clinical judgment. Hypomagnesemia is frequently associated with hypokalemia and hypocalcemia; hypermagnesemia most often occurs in patients with acute or chronic renal failure. Hypomagnesemia presents as neuromuscular, central nervous system and cardiac abnormalities. Inadequate dietary intake of magnesium occurs in alcoholism, catabolic states and gastrointestinal diseases. Intravenous administration of magnesium can cause neuromuscular paralysis and cardiac arrhythmias. PMID- 2195860 TI - Secondary prevention after high-risk acute myocardial infarction with low-dose acebutolol. AB - Acebutolol et Prevention Secondaire de l'Infarctus (APSI), a randomized, placebo controlled trial, was designed to test long-term acebutolol, 200 mg twice daily, a beta blocker with mild intrinsic sympathomimetic activity, in the prevention of late death in high-risk postacute myocardial infarction (AMI) patients. APSI was planned because patients with a death rate greater than 20% have not been enrolled in significant numbers in previous trials and in such high-risk patients, it remained to be proven that beta blockers have a beneficial effect. Patients with an expected average risk of greater than 20% were to be selected based on clinical criteria. At the time of the second interim analysis, the placebo group 1-year mortality was much lower than expected (12%). The ethical board recommended to stop the trial: 309 patients had been allocated to placebo, 298 to acebutolol. The average delay between onset of symptoms and inclusion was 10.5 days. The average follow-up was 318 days after inclusion. About the same number of patients were discontinued from study treatment in both groups. All patients were included in the analysis. There were 17 deaths in the acebutolol group and 34 in the placebo group, a 48% decrease (p = 0.019). The vascular mortality decreased by 58% (p = 0.006), the highest ever observed with a beta blocker. All cardiovascular causes of death, including congestive heart failure, were less frequent in the acebutolol group. Although the objective was not achieved, APSI patients were at a higher risk than the average of the 9 previous trials with beta blockers (12% instead of 7%). In addition, the total mortality reduction did not decrease in 9 subgroups with increasing mortality risk from 2 to 23%. APSI shows that moderately severe postAMI patients can benefit from a beta-blocking treatment and a beta-blocker with mild intrinsic sympathomimetic activity can be effective. PMID- 2195861 TI - Effects of early intervention with low-dose aspirin (100 mg) on infarct size, reinfarction and mortality in anterior wall acute myocardial infarction. AB - Recently, it was shown that aspirin given early in acute myocardial infarction (AMI) improves hospital survival, but the mechanisms involved are unclear. In a prospective, randomized placebo-controlled trial, the influence of early intervention with low-dose aspirin (100 mg/day) on infarct size and clinical outcome was studied in 100 consecutive patients with first anterior wall AMI. Infarct size was calculated by cumulative lactate dehydrogenase release in the first 72 hours after admission and was found to be (mean +/- standard deviation) 1,431 +/- 782 U/liter in the aspirin group (n = 50) and 1,592 +/- 1,082 U/liter in the placebo group (n = 50, p = 0.35). The study medication was given for 3 months, during which mortality was 10 (20%) in the aspirin patients and 12 (24%) in the placebo patients (p = 0.65). However, reinfarction occurred in 2 patients (4%) in the aspirin group and in 9 (18%) in the placebo group (p less than 0.03). Early intervention with low-dose aspirin showed, in comparison to placebo, a 10% decrease of infarct size, but this difference was not statistically significant. However, early low-dose aspirin effectively decreased the risk of reinfarction. Therefore, the favor able results of early aspirin on mortality in acute myocardial infarction are probably due more to prevention of reinfarction than to decrease of infarct size. PMID- 2195862 TI - Beneficial effect of magnesium sulfate in acute myocardial infarction. AB - The effects of magnesium on the incidence of arrhythmias and on mortality were evaluated in 103 patients with documented acute myocardial infarction (AMI) in a randomized, double-blind, placebo-controlled study. Fifty patients received a magnesium infusion for 48 hours and 53 received only the vehicle (isotonic glucose) as placebo. The baseline characteristics of the population were similar in the 2 groups. Tachyarrhythmias requiring drug therapy were recorded in 32% of the patients in the magnesium group and in 45% of the placebo group. Conduction disturbances were found in 23% of the placebo group as compared to 14% in the magnesium group. The intrahospital mortality was 2% (1 patient) in the magnesium group, compared to 17% (9 patients) in the placebo group (p less than 0.01). No adverse effects were observed during and after the magnesium infusion. These data support a possible protective role of magnesium in patients with AMI. PMID- 2195863 TI - Effect of dipyridamole at the usual oral dose on exercise-induced myocardial ischemia in stable angina pectoris. AB - A randomized, double-blind, placebo-controlled study was performed to investigate the effect of dipyridamole at a usual oral dose of 150 mg/day on 18 patients with angina pectoris and positive treadmill exercise electrocardiography. After their angina pectoris was stabilized in phase 1, the patients were randomly assigned to sequence group A or B. Group A received a placebo 3 times daily in phase 2 and then 50 mg of dipyridamole 3 times daily in phase 3. Group B received the treatment in the reverse order. The degree of ST depression and the threshold for angina pectoris in treadmill exercise electrocardiography, which was performed on the last days of phases 2 and 3, were compared. The mean duration of exercise was 5 minutes and 23 seconds during dipyridamole and 5 minutes and 13 seconds during placebo administration, with no significant difference. Dipyridamole caused an aggravating effect on the ST change (earlier appearance of ST depression and/or deeper total sum of ST depression at the end of the exercise) in 3 patients, a salutary effect in 5 and no effect in 10. Dipyridamole decreased the threshold for angina pectoris in 5 patients, increased it in 6 and did not change it in 7. To summarize, dipyridamole showed adverse effects (aggravative effects on the ST change and/or on the threshold for angina pectoris) in 6 patients, beneficial effects in 8 and no effect in 4. A usual oral dose of dipyridamole induced myocardial ischemia during exercise in some patients while it improved it in a similar number of patients. PMID- 2195864 TI - Reduction of myocardial ischemia during percutaneous transluminal coronary angioplasty with oxygenated Fluosol. AB - The effects of perfusion of an oxygen-carrying perfluorochemical emulsion (Fluosol) in alleviating symptoms of myocardial ischemia during balloon occlusion were examined in a multicenter trial of 245 patients. Severe anginal pain occurred less frequently in patients receiving Fluosol perfusion (21%) than in those receiving routine angioplasty (34%) (p less than 0.05). ST-segment changes at balloon deflation in routine angioplasty patients were significantly greater than in patients who received oxygenated Fluosol perfusion (2.2 +/- 1.2 vs 1.7 +/ 0.9 mm; p less than 0.03). Profound regional wall dysfunction (-561 +/- 224 U) was observed in routine angioplasty patients by 2-dimensional echocardiography. Patients receiving oxygenated Fluosol perfusion, however, maintained near baseline levels of ventricular function (-61 +/- 335 U) during occlusion (p less than 0.0001). Mean global left ventricular ejection fraction was preserved at baseline levels during balloon inflation in patients perfused with oxygenated Fluosol but decreased significantly (p less than 0.001) during occlusion in routine angioplasty patients. A total of 26 complications (19 routine group; 7 perfusion group) was reported. Adverse responses to the perfusate were infrequent, occurring in 1.6 and 2.0% of patients after the test dose and during perfusion, respectively. Thus, transcatheter perfusion with an oxygen-carrying perfluorochemical emulsion is effective in alleviating myocardial ischemia during angioplasty and can be safely administered in this patient population. PMID- 2195866 TI - Rationale against the drug treatment of marginal diastolic systemic hypertension. PMID- 2195865 TI - Studies of left ventricular dysfunction (SOLVD)--rationale, design and methods: two trials that evaluate the effect of enalapril in patients with reduced ejection fraction. AB - The Studies of Left Ventricular Dysfunction (SOLVD) is an extensive program of research that has 3 components. (1) Two large double-blind randomized trials evaluate the effects of enalapril on mortality, morbidity and quality of life of patients with left ventricular (LV) dysfunction with overt congestive heart failure (CHF) (Treatment Trial in 2,500 patients) and without overt CHF (Prevention Trial in 4,600 patients). (2) Seven detailed sub-studies evaluate the effect of enalapril on a number of intermediate outcomes such as right and LV function and hemodynamics, LV mass and wall stress, hormones, arrhythmias, exercise capacity and quality of life in subsets of patients in the 2 large trials. (3) Finally, a registry of 6,336 patients with congestive heart failure or LV dysfunction is designed to describe the clinical course of an unselected group of patients. The rationale and design of a tiered approach to clinical trials that are large enough to provide reliable information on mortality and morbidity, yet provide relevant information on other endpoints, are described. PMID- 2195867 TI - Fibrinolysis and fibrinogenolysis in liver disease. AB - Patients with liver disease frequently have hemostatic abnormalities which include accelerated fibrinolysis. In order to assess the fibrinolytic state in liver disease, plasma levels of fibrinogenolysis products (FgDP), fibrinolysis products (FbDP), and fibrinogenolysis plus fibrinolysis products (TDP) were measured with newly developed enzyme-linked immunosorbent assays based on monoclonal antibodies in 36 patients with liver disease (six patients with acute hepatitis, seven with chronic hepatitis, ten with liver cirrhosis, 11 with hepatocellular carcinoma, and two with intrahepatic cholestasis). As compared with healthy subjects, mean plasma levels of FbDP (1,083 +/- SD 1,254 vs. 236 +/- 100 ng/ml, P = 0.005) and TDP (1,773 +/- 1,814 vs. 669 +/- 212 ng/ml, P = 0.001) were significantly elevated in patients with liver disease, whereas FgDP was normal (389 +/- 202 vs. 396 +/- 132 ng/ml, P = 0.87). Plasma FbDP correlated very well with TDP (r = 0.986, P less than 0.00001) in liver disease. In addition, FbDP and TDP but not FgDP correlated with plasma concentrations of thrombin antithrombin III complex. When plotted by the disease categories, the magnitude of elevations of FbDP and TDP was the most prominent in acute hepatitis followed by hepatocellular carcinoma. These findings indicate that activation of fibrinolysis occurs following thrombin generation, but increased primary fibrinogenolysis is rare in liver disease. PMID- 2195868 TI - Specific identification of fibrin(ogen) degradation products in plasma and serum using blotting and peroxidase labeled antiserum. AB - We describe a method for identifying fibrinogen and fibrin split products using electrophoresis on agarose gel with sodium dodecyl sulfate (SDS) followed by blotting in nitrocellulose paper. Detection of these derivatives after blotting is accomplished with peroxidase-conjugated rather than by isotopically labeled antibodies. This technique can detect diverse fibrinogen derivatives produced in vivo or in vitro by the combined action of thrombin, plasmin, and factor XIII. This methodology is applicable to plasma, serum, and other body fluids including urine and ascitic fluid. This sensitive and specific assay, distinguishing the products of cross-linked fibrin from those of fibrinogen and detecting fibrin polymers in plasma, can be achieved without the use of radioactivity. PMID- 2195869 TI - Idiopathic myelofibrosis: a clinical study of 80 patients. AB - A series of 122 consecutive patients with bone marrow fibrosis initially referred or categorized as idiopathic myelofibrosis is described. After a clinical and pathological review 14 patients were classified as postpolycythaemic myelofibrosis and 7 patients as a transitional myeloproliferative disorder. In 13 patients a diagnosis of hairy cell leukaemia was made, 3 patients had malignant lymphoma, 2 had malignant histiocytosis, and 1 patient had systemic lupus erythematosus with myelofibrosis. Two patients were excluded for further analysis owing to insufficient data. In the remaining 80 patients a diagnosis of idiopathic myelofibrosis was made. The clinical and laboratory findings in this series of patients are presented and compared to those in previous series. Infectious, cardiovascular, thromboembolic, and haemorrhagic complications were frequent, being recorded in 63%, 50%, 40%, and 33% of the patients, respectively. Various autoimmune phenomena were found in a proportion of the patients, but none had clinical evidence of connective tissue disease. Fifteen patients (19%) had a syndrome of acute myelofibrosis. The diagnostic criteria for this disease entity and its place within the spectrum of myeloproliferative disorders are discussed. In the present series acute myelofibrosis was found to encompass various transitional stages toward the evolution of acute leukaemia. It is proposed that acute or malignant myelofibrosis is considered as an acute variant of idiopathic myelofibrosis. Within this syndrome the acute variant seems to be far more common than previously recognized, which may also explain the marked clinical heterogeneity of the myelofibrosis/osteomyelosclerosis syndrome in this and most previous series. PMID- 2195870 TI - Evaluation of kidney function in renal transplant patients receiving long-term cyclosporine. AB - We prospectively assessed renal function in a group of 29 renal transplant patients receiving cyclosporine (CsA) in order to determine the course of their renal function over time and the relationship between different markers of glomerular function. We measured serum creatinine, DPTA, and creatinine clearances, and urinary albumin excretion. The clinical course of 24 patients (83%) permitted repeat studies over a period of 32 +/- 1 (SEM) months, and in these patients DTPA clearance, creatinine clearance, and the serum creatinine concentration did not vary with time. Five of the patients (17%) lost their grafts and returned to dialysis. On initial evaluation patients who lost their grafts had a lower DPTA clearance than those whose function was maintained (29 +/ 3 v 46 +/- 2 mL/min/1.73 m2 body surface area [BSA], respectively, P less than 0.005) and all of them had a DTPA clearance of less than 40 mL/min/1.73 m2 BSA. There was an inverse correlation between the log of the urinary albumin excretion and the DTPA clearance (n = 33, r = -0.59, P less than 0.001), a direct correlation with the serum creatinine concentration (N = 33, r = 0.89, P less than 0.0001), but no correlation with time after transplantation. Thus, despite the continued use of CsA, renal function over time was stable in patients who underwent repeated studies, as was the relationship between the DTPA clearance and the clinically used markers of transplant function, the serum creatinine concentration, and the creatinine clearance. PMID- 2195871 TI - Long-term outcome of renal transplantation in autosomal dominant polycystic kidney disease. AB - This study was performed to determine the long-term outcome of renal transplantation in 54 patients with end-stage renal failure secondary to autosomal dominant polycystic kidney disease (ADPKD) and in 107 patients with renal diseases other than ADPKD or diabetes mellitus matched by gender, age, year of transplantation, and source of the allograft. The overall patient survival and patient survival with a functioning first renal allograft were similar in both groups. Infection and cardiovascular accidents were the leading causes of early and late death in both groups. No cause of death was greatly overrepresented in the ADPKD group. Serious complications from extrarenal manifestations of ADPKD following renal transplantation included a ruptured intracranial aneurysm in one patient, a dissection of the ascending thoracic aorta in one patient, and infected hepatic cysts in two patients. Neoplasia (other than skin or cervical) occurred in four ADPKD patients and in one control patient and included one lymphoma in each group. Two ADPKD and one control patient had monoclonal gammopathies of undetermined significance. No complications related to the retention of native kidneys were detected in 12 ADPKD patients with a mean follow up of 3 years. Cysts were observed in the renal allografts of some patients in both groups at autopsy and in a prospective computed tomography (CT) study of the allograft. However, we failed to detect a significant difference in the occurrence and number of the cysts between ADPKD and control patients. PMID- 2195872 TI - Evaluation of renal transplant dysfunction by duplex Doppler sonography: a prospective study and review of the literature. AB - A disconcertingly wide variation exists in the literature as to the accuracy of duplex Doppler sonography in the detection of acute renal transplant rejection. Sensitivities range from 9% to 76%. In an attempt to explain the disparity of results, we undertook a double-blind prospective study of the accuracy of duplex Doppler ultrasound in the detection of acute rejection in renal transplants. We scanned 49 consecutive patients with a total of 65 biopsies; 46 biopsies in 33 consecutive patients were included in our study. In our population, the prevalence of acute rejection was 61% (28/46). Using a resistive index (RI) cutoff of greater than 0.90 based on the main renal artery flow pattern, the sensitivity of our test was 43%, with a 67% specificity. The positive predictive value was 67%. Our results are contrasted and compared with the published data from other groups in a critical survey of the literature. We conclude that duplex Doppler sonography alone is inadequate to evaluate acute rejection in renal transplants. PMID- 2195873 TI - A study of beta 2-microglobulin skin deposits in dialyzed patients and healthy controls. AB - This study reports on beta 2-microglobulin (beta 2M) deposits in the skin of 12 uremic patients and three kidney transplant recipients compared with eight healthy controls. Uremic patients were treated by hemodialysis (HD), hemofiltration (HF), hemodiafiltration (HDF), or continuous ambulatory peritoneal dialysis (CAPD) for a period lasting from 1 to 19 years. Congo red staining of the skin was negative in patients and controls. However, immunofluorescent staining with an anti-beta 2-microglobulin monoclonal antibody was positive in the skin of all patients and of six of the eight controls. Beta 2M skin deposition is more intense in patients than in controls and increases with patient age and the duration of dialysis. A stron correlation is observed between the extent of skin beta 2M deposits and clinical manifestations due to beta 2M deposits in internal organs. However, no correlation is found between beta 2M skin deposits and sex or beta 2M serum levels. PMID- 2195874 TI - Expression of renin and its mRNA in the adult rat kidney with chronic ureteral obstruction. AB - Angiotensin II has been implicated in mediating renal vasoconstriction resulting from chronic unilateral ureteral obstruction (UUO) in both mature and developing animals. We have previously shown that chronic neonatal UUO results in increased distribution of renin and its mRNA in the obstructed kidney, as well as of immunoreactive renin in the intact opposite kidney. The present study was designed to evaluate the effects of 24 hours versus 4 weeks of UUO on the distribution of renin mRNA and its protein in the adult rat kidney. Renin was detected by immunocytochemistry using a polyclonal anti-rat renin antibody. Renin mRNA was localized by in situ hybridization to an oligonucleotide complementary to renin mRNA. UUO of 24 hours' or 4 weeks' duration did not alter the distribution of renin and its mRNA in the obstructed kidneys as compared with sham-operated kidneys, although kidneys obstructed for 4 weeks had a significant increase in the percent of renin-containing juxtaglomerular apparatuses (JCA) when compared with the intact opposite kidneys (P less than 0.05). Compensatory hypertrophy was not present in the intact opposite kidneys after 24 hours of UUO and distribution of renin gene expression was not altered at that time. However, 4 weeks following contralateral UUO, the intact kidneys were hypertrophied and showed a decrease in renin gene expression relative to the obstructed and sham operated kidneys. We conclude that unlike UUO during early development, chronic UUO in the mature animal does not activate renin gene expression nor alter renin distribution in the obstructed kidneys. Renin gene expression is suppressed in the hypertrophied kidney with prolonged contralateral UUO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2195875 TI - Acquired immunodeficiency syndrome and the kidney. AB - Initial autopsy studies concerned primarily with the systemic manifestations of the acquired immunodeficiency syndrome (AIDS) did not indicate that significant renal problems were likely to occur in AIDS patients. However, several recent studies have suggested that important renal and electrolyte disorders develop frequently in at least some groups of AIDS patients. In this report, we review current information concerning such disorders and describe our study of the frequency and types of renal lesions in the first 50 AIDS patients undergoing autopsy at this institution. We conclude that a number of renal lesions and electrolyte abnormalities occur in AIDS patients, although the frequency and nature of these problems vary considerably from center to center. Studies from several centers, including our own, indicate that AIDS patients are particularly likely to develop tubulointerstitial lesions (such as nephrocalcinosis and interstitial nephritis) and electrolyte disorders. Additional studies from specific centers in New York City, Miami, Detroit, and Los Angeles indicate that AIDS patients can also develop glomerular lesions, including a variant of focal and segmental glomerulosclerosis (FSGS) associated with heavy proteinuria and rapidly progressive renal failure. Although FSGS is not commonly observed in all centers, AIDS patients with this lesion appear to have a distinctive combination of clinical and pathological features, suggesting that they have a specific "human immunodeficiency virus (HIV)-associated" nephropathy. Preliminary evidence suggests that this lesion may be related to direct renal HIV infection, although confirmation of this possibility is needed. The approach to the AIDS patient with renal disease should involve correction of reversible disorders and consideration of dialysis as necessary. PMID- 2195876 TI - Acquired immunodeficiency syndrome and renal disease: report of the National Kidney Foundation-National Institutes of Health Task Force on AIDS and Kidney Disease. PMID- 2195878 TI - Correlation of glomerular basement membrane alterations with clinical data in progressive hereditary nephritis (Alport's syndrome). AB - Electron microscopic examination of glomerular basement membrane (GBM) was performed in 19 patients whose morphological changes as well as clinical features indicated the diagnosis of progressive hereditary nephritis (Alport's syndrome). The percentage of characteristically thickened and split and of thin GBM portions was determined in all the cases. The clinical course was more severe in males, which corresponded to higher rate of GBM alterations. In males, 58% of GBM was thickened and split and 24% was thin, while in females, the reverse was true, 28% was split and 48% of GBM was thin. There was a positive correlation of the split lesions and age in males, but not in females. The degree of splitting was directly proportional to the grade of proteinuria, while GBM thinning did not significantly correlate with proteinuria. PMID- 2195877 TI - Anthropometric norms for the dialysis population. AB - Although norms are available for healthy subjects, it is preferable, when interpreting anthropometry in individual dialysis patients, to compare measurements with norms for the stable dialysis population. The purpose of this study was to develop these reference anthropometric norms for dialysis patients. Triceps skinfold (TSF), subscapular skinfold (SSF), and mid-upper arm circumference (MUAC) measurements were made in 925 patients with no major illness, who were being treated by chronic maintenance dialysis in 27 dialysis facilities. Of these, 609 patients treated by hemodialysis (HD) were in subgroups large enough to compare with those from the National Health and Nutrition Examination Survey (NHANES) II. Diabetic patients were significantly different from nondiabetic patients; therefore, the two groups were analyzed separately. Male HD patients (diabetic and nondiabetic) did not differ significantly from the NHANES II data. Diabetic HD females did not differ significantly from the NHANES II data, except for the TSF of black women older than 55 years. Measurements of nondiabetic HD females (black and white) were significantly below the NHANES II data. In 138 continuous ambulatory peritoneal dialysis (CAPD) patients, measurements were similar to those of HD patients. PMID- 2195879 TI - Cell proliferation in the end-stage kidney. PMID- 2195880 TI - Number of women holding leadership positions in ASHP from 1942 to 1989. PMID- 2195881 TI - Factors influencing restenosis after coronary angioplasty. AB - In 1989, it is estimated that coronary angioplasty will be performed in more than 250,000 patients for the relief of ischemic symptoms due to coronary artery disease. Despite its widespread acceptance, the overall success of coronary angioplasty has been limited by the development of recurrent ischemia due to restenosis in approximately 30% of patients undergoing this procedure. Restenosis, due to an excessive fibroproliferative response to endothelial denudation and vessel injury that occurs at the time of vessel dilatation, usually develops within six months after coronary angioplasty. Although a variety of clinical, anatomic, and procedural factors may identify patients at risk for the development of restenosis, intensive pharmacologic and, recently, mechanical interventions have generally been ineffective in its prevention. New therapies, including inhibition of platelet aggregation, receptor blockade of specific vasoactive mediators, and growth factor modification, appear to be promising methods for the future in the prevention of restenosis. Moreover, further refinement of the use of mechanical techniques such as excisional atherectomy, laser, and endoluminal stents may diminish the degree of vascular damage that occurs at the time of vessel dilatation, and attenuate the biologic processes that ultimately culminate in restenosis. PMID- 2195882 TI - Current role of the automatic implantable cardioverter-defibrillator in the treatment of life-threatening ventricular arrhythmias. AB - The automatic implantable cardioverter-defibrillator (AICD) has become widely accepted as an effective treatment for patients with ventricular fibrillation or hemodynamically unstable ventricular tachycardia. The use of an antitachycardia pacemaker in combination with the AICD has also provided an effective therapy for patients with hemodynamically stable ventricular tachycardia that is refractory to antiarrhythmic drugs. The risk of sudden cardiac death following implantation of an AICD in patients with malignant ventricular tachyarrhythmias is lower than has been observed during treatment with amiodarone, direct operations for ventricular tachycardia, or conventional antiarrhythmic drug therapy guided by either noninvasive or invasive electrophysiologic testing. Although the impact of this device on the subsequent risk of sudden death is widely recognized, the effect on overall mortality is more controversial. Careful preoperative evaluation, electrophysiologic testing, and patient selection are critical for the successful use of antitachycardia devices. Clinical trials of AICDs with the capability for antitachycardia and bradycardia pacing, programmable pulse energy and waveform, and extensive memory will soon begin in the United States. Despite considerable limitations in the currently available technology, future developments in implantable antitachycardia devices offer the greatest promise for improving the outcome of patients at risk for sudden cardiac death from ventricular arrhythmias. PMID- 2195883 TI - Survival in congestive heart failure: have we made a difference? AB - Congestive heart failure (CHF) affects approximately 400,000 new patients each year in the United States, resulting in death in more than 50% within five years, with traditional therapy including digitalis and diuretics. The aging of the population will only serve to aggravate this problem. Surgical treatment of CHF is a viable option in a minority of cases; a total of no more than 2,000 heart transplantation procedures were performed in the United States in 1988. Therefore, if survival is to improve in patients with CHF, effective alternative medical therapy may need to be added to or substituted for more traditional therapy. Vasodilator therapy with the angiotensin-converting enzyme inhibitors captopril and enalapril, or the combination of hydralazine and isosorbide dinitrate, improves survival in patients with severe heart failure when added to treatment with digitalis and diuretics. Nevertheless, the mortality rate remains extremely high once this stage of the disease process is reached. The prevention of left ventricular dilatation and remodeling, before the occurrence of overt heart failure, is the focus of much attention. Interventions that limit or interrupt the disease process at an even earlier stage will be necessary to make a major impact on survival. PMID- 2195884 TI - Systemic lupus erythematosus presenting as acute severe mitral regurgitation. PMID- 2195885 TI - Long-term survival from acute myocardial infarction: salutary effect of an open coronary vessel. PMID- 2195887 TI - Primary group A streptococcal peritonitis in adults. PMID- 2195886 TI - Prognosis of patients hospitalized with community-acquired pneumonia. AB - PURPOSE: Our purpose was to determine which clinical features predict short-term mortality in patients with community-acquired pneumonia. PATIENTS AND METHODS: We conducted a prospective multicenter study of 347 patients hospitalized in Pittsburgh (the derivation cohort) and 253 hospitalized and ambulatory patients in Boston (the validation cohort) with clinical and radiographic evidence of pneumonia. Patients in the derivation cohort underwent an extensive microbiologic evaluation including bacteriologic sputum culture, blood cultures, direct fluorescent antibody testing for Legionella species, and serologic testing for Mycoplasma pneumoniae, Legionella species, and Chlamydia TWAR. RESULTS: The overall mortality was 18% in the derivation cohort and 13.2% in the validation cohort. We identified five independent predictors of mortality in the derivation cohort: pleuritic chest pain (risk ratio, 0.4; 95% confidence interval [CI], 0.17 to 0.99), mental status changes (risk ratio, 2.6; 95% CI, 1.4 to 4.6), a severe vital sign abnormality (risk ratio, 2.1; 95% CI 1.2 to 3.6), neoplastic disease (risk ratio, 5.0; 95% CI, 2.7 to 9.1), and "high-risk" pneumonia etiology (risk ratio, 2.8; 95% CI, 1.6 to 5.0). A mortality index based on these factors accurately classified patients into five risk classes of increasing mortality. In the derivation cohort, the 6-week mortality rates were 0% in class I, 2.9% in class II, 13.1% in class III, 32.7% in class IV, and 89.5% in class V. There was little deterioration in the predictive accuracy of the model when tested in the validation cohort: mortality was 2.2% in class I, 0% in class II, 13.5% in class III, 33.3% in class IV, and 55.6% in class V. CONCLUSIONS: This prognostic classification may help direct triage decisions, assess appropriateness of care, and guide the design and analysis of therapeutic trials in patients with community-acquired pneumonia. PMID- 2195888 TI - Disseminated cryptococcosis diagnosed on peripheral blood smear in a patient with acquired immunodeficiency syndrome. PMID- 2195889 TI - Outcomes in patients with myocardial infarction who are initially admitted to stepdown units: data from the Multicenter Chest Pain Study. AB - PURPOSE: To assess whether the admission of patients with chest pain to a stepdown unit would jeopardize the outcome of those patients who ultimately "ruled in" for a myocardial infarction. PATIENTS AND METHODS: We compared the risk of an adverse outcome in initially uncomplicated, "rule-out myocardial infarction" patients who were admitted directly to a stepdown unit (n = 58) or to a coronary care unit (n = 409) at 6 hospitals and who then ultimately "ruled in" for a myocardial infarction. RESULTS: An adverse outcome (death, serious complication, or invasive intervention) occurred in 16 (28%) stepdown unit patients compared with 159 (39%) coronary care unit patients. Among patients eligible for initial care in either location, the risk of an adverse outcome after controlling for clinical characteristics was similar in the two groups using each of two different multivariate approaches. CONCLUSION: Although our study was not of sufficient size to exclude the possibility of a small benefit from initial triage to a coronary care unit, our data suggest that (1) admission of initially uncomplicated chest pain patients with a relatively low probability of acute myocardial infarction to a stepdown unit does not seriously jeopardize those who eventually "rule in" for myocardial infarction; and (2) larger observational or randomized studies, which could reduce the residual possibility of somewhat higher risk in the stepdown unit, would be ethical to perform. PMID- 2195891 TI - Neurologic manifestations of giant cell arteritis. AB - Giant cell arteritis (GCA) is a common vasculitic disease in the elderly, with a multitude of neurologic manifestations including, but not limited to, stroke and blindness. Many uncommon manifestations are often unrecognized and proper diagnosis and treatment delayed. This review focuses on the pathophysiology and neurologic symptoms of GCA, with special emphasis on the diversity of ocular involvement. PMID- 2195890 TI - Once-daily dosing regimen for aminoglycoside plus beta-lactam combination therapy of serious bacterial infections: comparative trial with netilmicin plus ceftriaxone. AB - PURPOSE: Once-daily dosing of aminoglycosides has been suggested to improve their efficacy and reduce their toxicity. To test the clinical validity of this suggestion, we conducted a prospective, randomized trial comparing a conventional multiple-daily-dosing regimen of netilmicin with once-daily administration of the same total daily dose of this aminoglycoside. PATIENTS AND METHODS: We enrolled 141 predominantly elderly patients with severe bacterial infections. All patients received once-daily doses of 2 g ceftriaxone, in addition to netilmicin. RESULTS: Patients randomized to either of the two dosing strategies were comparable regarding age, APACHE II score, concomitant diseases, infection site, and rate of culture-proven bacteremia. Netilmicin treatment did not differ significantly in mean daily dose per kg body weight and days of therapy between the two treatment arms. Compared to patients receiving conventional doses, patients treated with a once-daily dose had higher serum peak netilmicin levels and lower trough levels. Outcome of infection and mortality were not influenced by dosing strategy. Although the overall incidence of nephrotoxicity was similar in both groups (16%), the occurrence of nephrotoxicity in patients treated with once-daily doses of netilmicin was significantly shifted to those given prolonged treatment, i.e., beyond 9 days. Auditory toxicity was documented in one patient treated with conventional doses and two patients treated with once-daily doses. CONCLUSION: Once-daily dosing of an aminoglycoside plus a long-acting cephalosporin in these patients constituted cost-effective and safe treatment for severe bacterial infections. Netilmicin-induced toxicity may be reduced by using once-daily dosing regimens and limiting the duration of treatment. PMID- 2195892 TI - Advances in primary sclerosing cholangitis. AB - Primary sclerosing cholangitis is an increasingly recognized chronic cholestatic liver disease. It frequently occurs in association with chronic ulcerative colitis and is characterized by inflammation and fibrosis of the intrahepatic and extrahepatic bile ducts. The cause is unknown, although many mechanisms have been considered, including infectious, toxic, and immunologic. The prognosis varies. No adequate treatment exists, although a number of potential treatments have been evaluated in uncontrolled trials, and the results of controlled trials have only recently been reported. Liver transplantation has recently been shown to be an effective treatment for end-stage disease. These various advances in our understanding of primary sclerosing cholangitis are reviewed. PMID- 2195893 TI - Recurrent conjunctival papilloma causing nasolacrimal duct obstruction. AB - We treated two patients who had recurrent conjunctival papillomas that invaded the nasolacrimal sac and caused complete canalicular and nasolacrimal duct obstruction. The ophthalmologist should be aware of the possibility of a conjunctival papilloma invading the lacrimal sac when treating patients with conjunctival papillomas. Excision should be complete, and adjunctive therapy such as cryotherapy should be considered to reduce the chance of tumor recurrence. PMID- 2195894 TI - Simultaneous bilateral diffuse melanocytic uveal hyperplasia. AB - A 52-year-old woman noted loss of vision in August 1984. Clinical examination disclosed iris cysts and ciliary body cysts, macular edema, and uveal nevi. Cataract extraction and pressure-lowering operations were required in both eyes because of a tumor-induced angle-closure glaucoma. Vision, however, progressively decreased to light perception in each eye. Both eyes were finally enucleated because a malignant melanoma could not be ruled out, though iris tissue obtained in 1985 suggested a nevuslike process. Histologic study indicated a bilateral uveal hyperplasia. Results of light and electron microscopy, immunologic studies, and suspension cell culture suggested that the uveal hyperplasia was more likely a melanoma of low malignancy than a nevuslike process. We could not detect an extraocular primary tumor and assumed that this condition constituted an oncogenic syndrome. PMID- 2195895 TI - The use of crossed polarized filters in the measurement of the relative afferent pupillary defect. AB - We used crossed polarized neutral density filters to quantitate relative afferent pupillary defects. To prove reproducibility, the relative afferent pupillary defects of 20 patients were measured with this technique by two independent observers. There was no statistically significant difference between the two measurements. Relative afferent pupillary defects as low as 0.03 log unit were easily measured. These filters offer a convenient and reproducible technique that is more sensitive than the use of neutral density filters. PMID- 2195896 TI - Artificially produced quadrantanopsia in computed visual field testing. PMID- 2195897 TI - Delayed increased intraocular pressure after Nd:YAG laser posterior capsulotomy in a patient treated with apraclonidine. PMID- 2195898 TI - Tight scleral flap trabeculectomy with postoperative laser suture lysis. PMID- 2195899 TI - Dilemmas in the management of suicidal behavior in individuals with borderline personality disorder. AB - Managing suicidal behavior of individuals with borderline personality disorder presents both therapeutic and ethical/legal dilemmas. It is argued in this paper that clinicians treating borderline individuals need to carefully discriminate "acute" from "chronic" suicidal states. For "acute" suicidal situations, traditional management approaches are appropriate. However, for "chronic" situations, common among borderline individuals, traditional management approaches may be therapeutically counterproductive. A number of proposals for managing chronic suicidal behavior are reviewed. Unfortunately, current ethical standards and laws have evolved from considering suicide in an "acute" context and are insensitive to the "chronic" situation. Recommendations are made for clinicians to effectively manage chronic suicidal behaviors within present ethical and legal guidelines, and some suggestions for legal reform are offered. PMID- 2195900 TI - The functional dynamics of the narcissistic personality. AB - The majority of works on Narcissistic Personality Disorder analyze etiological, pathogenetic, structural, and/or clinical-diagnostic aspects of pathological narcissism. This article analyzes the functional dynamics of the narcissistic personality. More precisely, the author discusses the origin of chronically fragile (low) self-esteem of narcissistic personalities, as well as the uniquely narcissistic "way of life," which includes narcissistic mirroring in external objects and narcissistic object choice; the two maneuvers enable narcissistic persons to "confirm" their grandiose self-importance and significance in the external world. Next, stereotyped cycles (zest alternating with disappointment) that reflect narcissistic persons' futile attempts to feed their grandiose expectations, as well as pessimistic mood (characteristic emotional state of decompensated narcissistic persons) are discussed. The clinical features of Narcissistic Personality Disorder are systematized and presented in the framework of the accepted structural concept of this disorder at the end of the article. PMID- 2195901 TI - Enhancing the impact of therapeutic interventions. AB - A therapeutic intervention has impact if it reaches the patient's mind and remains available for times of need. Impact is the overcoming of attention, neglect and forgetfulness. Therapists enhance impact by: (a) building up patients' positive attention; (b) creating unusual and discrepant events; (c) strengthening the therapeutic message or the way it is conveyed; (d) drawing out patients' readiness for commitment and hard work; (e) creating bridges between therapy and the problem situation; (f) protecting the therapeutic message from trivializing and levelling events. These principles are nonspecific and are here illustrated by examples from widely different therapeutic approaches. Impact is not a substitute for the inherent value of a therapeutic message, but its lack can doom even our greatest inspirations. PMID- 2195902 TI - Malpractice in psychotherapy: an overview. AB - This paper gives a capsule review of the major issues on the subject of malpractice for individual practitioners of psychotherapy. It examines the elements necessary to support a malpractice claim and presents examples of cases in specific areas of liability. Historically, the field of psychotherapeutic malpractice was largely inactive. However, recent court rulings reveal that psychotherapists are no longer immune to malpractice suits. In decreasing order of the likelihood of the plantiffs being successful in their suits are cases involving the misuse of the therapeutic relationship, breach of confidentiality, and cases that involve prevention of harm to third parties and to patients themselves. Malpractice suits based on negligence in providing appropriate treatment are beginning to emerge and will probably increase in frequency as the efficacy of biological treatment is demonstrated. Available solutions to the problems of malpractice are discussed. It is suggested that in addition to the existing external sanctions, there is a need for consultation plus educational programs to enhance our ability to practice within the boundaries that the courts have set for us. PMID- 2195903 TI - Integrating individual and family treatment for outpatients vulnerable to psychosis. AB - Most clinicians favor family involvement in the treatment of adult outpatients who are at risk for major mental illness. New models for the family-oriented treatment of mental illness, particularly schizophreania, are, however, not readily adaptable to the situations encountered by practitioners working in clinics or private offices where one-to-one psychotherapy is the norm. This article describes a clinical model that is compatible with such an individualized outpatient practice (particularly for outpatients who are living with their family of origin or a spouse). The innovative feature of this model is the integration of the patient's family into the ongoing treatment on a regular basis, while continuing to maintain the primary focus on the patient and the therapist-patient relationship. To maintain a balanced response to the needs of both patient and family, prevent patient paranoia and family intrusiveness, and facilitate prompt and effective containment for patient losses of control, this model puts into place several mechanisms: (1) the scheduling of family meetings at predetermined times; (2) the establishment of protocol for handling unanticipated phone calls from family members; and (3) the creation of a three way therapist-patient-family contract for dealing with incipient emergencies. PMID- 2195904 TI - Hermeneutics for psychotherapists. AB - Hermeneutics as a method of approach has been used differently by many different authors, and in this paper I have reviewed the history and evolving employment of the hermeneutic approach. For the purposes of psychotherapists, the point of hermeneutics is that, in contrast to the natural sciences, it focusses away from the classical notion of the neutral independent observer (or subject or psychotherapist) as detached from the object of his or her study, the patient. All understanding in the human sciences is viewed by hermeneutics as arising out of a fusion of horizons between the investigator and the humans being investigated. The "knowledge" which arises from such an investigation is not some sort of immutable truth or essence, but is context dependent and a function of the "prejudices" which the investigator brings to the investigation. Diagnoses and formulations in the practice of psychotherapy, if the hermeneutic approach is employed, cannot be viewed as disease entities and natural science "facts," but rather as temporary formations that change with changing times, historical eras, cultures, and prevailing prejudices and practices. The problem of a hermeneutic psychiatry would be to steer between the Scylla of naive realism ignoring the major participation of the psychotherapist on the one hand, and the Charybdis of relativism, nihilism, and hopeless skepticism on the other. Much work remains to be done in order to clarify the role and limitations of hermeneutics, and to incorporate it into the clinical practice of psychotherapy, and this work must be done against the prevailing ideology of scientific materialism that characterizes our historical era. A hermeneutic psychiatry offers us the best hope of not losing sight of the methodological horizons that delimit our clinical work, and of widening these horizons so as to provide further understanding of our patients. PMID- 2195905 TI - Affect in psychodynamic psychotherapy. AB - The effectiveness of psychotherapy, in a generic sense, is no longer in doubt. There is also greater acceptance of the proposition that common elements in all approaches play a major role in therapeutic change. Accordingly, there is something to be said for teasing out some commonly accepted ingredients that effect change and for studying the nature of their involvement in psychodynamic psychotherapy whether it be long-term, short-term, crisis intervention, or whatever other type of therapy. With that in mind, it is proposed that affect and its vicissitudes lend themselves well to such investigation. PMID- 2195906 TI - Kettering Laboratory: a pioneer in lead research. PMID- 2195907 TI - Portal hypertension. W. Dean Warren, MD, Memorial issue. PMID- 2195908 TI - Surgical rescue for failures of cirrhotic sclerotherapy. AB - Bleeding from gastroesophageal varices remains the most devastating complication of the portal hypertensive syndrome. Endoscopic sclerotherapy has emerged as the best initial treatment for bleeding varices because surgery is obviated and survival may be improved. However, sclerotherapy will fail and surgical rescue will be required in at least a third of patients. There are two viable surgical rescue procedures: shunt surgery and liver transplantation. This paper summarizes the available data and concludes that there is a role for both procedures. PMID- 2195909 TI - Diagnosis and management of the Budd-Chiari syndrome. AB - Occlusion or obstruction of hepatic venous outflow results in the Budd-Chiari syndrome. The disorder should be suspected in any patient who suddenly develops massive ascites, and the diagnosis can be confirmed quickly and accurately by hepatic venography. In the absence of surgical intervention, survival is rare. Inferior venacavography and percutaneous liver biopsy can be performed safely in these patients, and both procedures provide useful information for the selection of appropriate surgical therapy. Most cases of the Budd-Chiari syndrome are amenable to mesocaval or mesoatrial shunting. Those patients with documented cirrhosis or fulminant hepatic failure are best managed by orthotopic liver transplantation. PMID- 2195910 TI - A hepatologist's view of variceal bleeding. AB - Patients with cirrhosis and esophagogastric varices have a 25% to 33% risk of initial variceal bleeding, a risk of up to 70% for recurrent variceal bleeding, and an associated mortality of up to 50%. Based on a review of prospective randomized trials, control of acute variceal bleeding should involve vasopressin plus nitroglycerin as indicated for minor bleeding episodes, sclerotherapy for more severe bleeding episodes, and staple transection of the esophagus for patients who do not respond to these initial measures. Emergency portasystemic shunt surgery cannot be recommended at this time. For prevention of recurrent variceal hemorrhage, the data support the use of nonselective beta-adrenergic blockers (propranolol or nadolol) for patients with good liver function (Child's class A and B) and the use of chronic sclerotherapy to obliterate esophageal varices for patients with decompensated cirrhosis (Child's class C). Surgical procedures should be reserved for failures of medical management. The use of beta adrenergic blockers offers the most promise for prevention of initial variceal bleeding. PMID- 2195911 TI - Status of sclerotherapy for variceal bleeding in 1990. AB - The enthusiasm for injection sclerotherapy over the last decade has almost certainly surpassed what was justified on the basis of objective evidence. This was most clearly emphasized by the widespread adoption of prophylactic sclerotherapy after the report of the first two trials, even though enough was known of the natural history of variceal hemorrhage in patients with cirrhosis to warrant caution. The use of sclerotherapy for an episode of variceal hemorrhage represents the role most supported by the available data. Diagnostic endoscopy, as an integral part of management, provides the optimum time to intervene with sclerotherapy. Sclerotherapy can then provide hemostasis in patients who are actively bleeding and prevent early rebleeding in those in whom bleeding has stopped spontaneously. The progression to long-term injection sclerotherapy is of proven benefit; however, doubts exist concerning the need for the intensive regimens currently in use. The continued use of long-term injection sclerotherapy is dependent not only on additional investigations, but also on the accumulating evidence arising from comparative studies encompassing other available therapy. PMID- 2195912 TI - Has sclerotherapy altered the management of patients with variceal bleeding? AB - Sclerotherapy is currently the primary treatment of choice for the majority of patients who present with esophageal variceal bleeding. Although it has altered the management of these patients, unanswered questions and controversies remain. Patients with acute variceal bleeding should preferably be treated in a specialized center. The primary treatment should be immediate sclerotherapy, when possible. Portosystemic shunts and esophageal transection should be reserved for the 5% to 10% of patients in whom sclerotherapy fails to control acute bleeding. There are several treatment options for long-term management after a variceal bleeding episode. Sclerotherapy is one option and has become the primary treatment in most major centers. All patients with end-stage liver disease must be considered for liver transplantation, and sclerotherapy should be the primary method of treatment in those who are selected. Pharmacologic therapy remains controversial. I propose that portosystemic shunts and devascularization and transection operations be reserved for those few patients in whom sclerotherapy fails to eradicate the varices and to prevent recurrent variceal bleeding. Patients in whom sclerotherapy is unsuccessful should be identified and treated early. PMID- 2195913 TI - The Emory perspective of the distal splenorenal shunt in 1990. AB - The distal splenorenal shunt (DSRS) has been extensively studied at Emory University over the past 18 years to define its role in the management of variceal bleeding. DSRS has been applied broadly in many different patient groups and has been evaluated in prospective randomized trials; thus, a considerable amount of data has accrued on the metabolic and hemodynamic consequences of selective variceal decompression. Its current role is defined as primary therapy for variceal bleeding in patients with portal vein thrombosis and good-risk patients with nonalcoholic cirrhosis. As a therapy for patients whose bleeding is not controlled by sclerotherapy, it should be used as the shunt procedure of choice, but patient evaluation must focus on the choice between DSRS and liver transplantation. PMID- 2195914 TI - Steroids in croup: do they increase the incidence of successful extubation? AB - Between January 1983 and July 1988, 2623 patients with croup were admitted to the Royal Children's Hospital, Melbourne. A total of 416 patients (16%) were admitted to the Intensive Care Unit and 176 of these patients required intubation. Of these patients 117 patients were successfully extubated at the first attempt and 59 needed reintubation. Of the patients who were reintubated 35 were given steroids prior to subsequent extubation attempts. Only one patient who had received steroids failed extubation. Of those who did not receive steroids 59% required reintubation. In patients with croup who fail the first extubation the results of this study suggest that steroids significantly increase the success of subsequent extubations. PMID- 2195915 TI - The fifty-sixth Bancroft Oration. "A transient popularity". Queensland's early anaesthetists. PMID- 2195916 TI - Adaptation of cancellous bone to aging and immobilization in the rat: a single photon absorptiometry and histomorphometry study. AB - Nine-month-old female rats were double-labeled with bone markers and subjected to right hindlimb immobilization or served as control for 0, 2, 10, 18, or 26 weeks. The right limb was immobilized against the abdomen, thus unloading it, while the left limb was overloaded during ambulation. Single photon absorptiometry and cancellous bone histomorphometry were performed on dissected intact femur and 20 microns-thick undecalcified specimens of the proximal tibial metaphysis. In the unloaded limb, immobilization-induced muscle and cancellous bone loss occurred rapidly before 10 weeks and stabilized at 50% less bone mass after 18 weeks. Unloading caused a negative bone balance from a combination of elevated bone resorption and depressed bone formation. At 2, 10, and 18 weeks of immobilization, the ratios of bone resorption to bone formation surfaces were 1.6, 1.5, and 1.3, respectively; at 26 weeks, the ratio was 1. The bone loss was accompanied by poorer trabecular architecture (trabecular number decreased and trabecular separation increased), reaching the maximum at 18 weeks and stabilizing thereafter. These observations are in general agreement with Frost's postulate for mechanical effects on lamellar bone remodeling, and the findings on disuse osteoporosis in man. Therefore, the one-legged immobilization model can be useful in studies of the mechanisms of structural adaptation to mechanical usage. PMID- 2195917 TI - Renin immunohistochemistry in the adrenal gland of the mouse fetus and neonate. AB - The development of renin-containing cells in fetal and neonatal adrenal glands of the mouse was studied using immunohistochemistry. On days 13-14 of gestation, immunoreactivity for renin was first observed in a few cortical cells of the gland, appearing as small patchy or granular reaction products in the perikaryon. The mitotic configurations of the cells demonstrating immunoreactivity were noted. On day 16 of gestation, a number of intensively immunoreactive cells were distributed in the aortal side of the cortical zone. On day 18 of gestation, and day 1 postparturition, a small number of potent immunoreactive cells were still found in the cortical area. Immunoreactivity of the cytoplasm was observed in the cells, some showing an intensive reaction and others possessing numerous tiny granules just below the cell membrane. On days 3, 5, and 7 after birth, no renin containing cells were found in the adrenal gland. The ratio of the numbers of renin-positive cells in certain areas to the numbers in the entire cortical area was significantly increased on day 16 of gestation, but there was no sexual difference in the ratios. The ratios were decreased subsequently until day 1 after birth. The possible significance of renin synthesis in specific adrenal cells in fetal life is discussed with respect to an important involvement of angiotensin II in the morphogenesis of the adrenal gland of the mouse. PMID- 2195918 TI - Golgi tendon organs in the proximal tendon of sheep extraocular muscles. AB - Sheep extraocular muscles were prepared for light and electron microscopy and their proximal tendons searched for Golgi tendon organs (GTO). An extensive aponeurotic lamina on the orbital surfaces contained numerous GTO 250-1350 microns in length with characteristic terminal form and relationship with collagen. They differed from usual GTO structure in containing large fluid-filled spaces dividing collagen into several well separated compartments and a muscle fiber entered and terminated in about one third of the receptors. The fibers, Felderstruktur in type, often penetrated deep within tendon organs, and in a few instances two or more fibers entered. This feature is shared by the rare GTO of monkey extraocular muscles. That the presence of GTO in the proximal tendons of extraocular muscles is previously unrecorded may be attributed to the practice of restricting attention to the long distal tendons. The possibility that receptors may be so placed in other species warrants further work especially in those purported to lack any receptor. PMID- 2195919 TI - Distribution of serotonin-immunoreactive cells around arteries arising from the common carotid artery in the chicken. AB - By using an immunoperoxidase method with antiserotonin antiserum, the distribution of serotonin-immunoreactive cells in the carotid body region was investigated in chickens. The thyroid gland, cranial and caudal parathyroid glands, carotid body, and ultimobranchial gland of chickens were located along the common carotid artery as a continuous series and were supplied with branches arising from the artery. Almost all chief cells of the chick carotid bodies were immunoreactive for serotonin. Furthermore, numerous serotonin-immunoreactive cells were widely distributed in the adventitial connective tissue around those arteries that issued from the common carotid artery to supply each endocrine organ, i.e., the carotid body artery, the esophagotracheobronchial artery, the ascending esophageal artery, and the inferior thyroid artery. These arteries usually arose by one trunk from the lateral aspect of the middle portion of the common carotid artery. The serotonin cells were most numerous around the carotid body artery and were dispersed along the whole length of the artery. In addition, they were detected around the common trunk of each artery and the roots of the ascending esophageal artery, the inferior thyroid artery, and the esophagotracheobronchial artery. The serotonin cells were also distributed in the tunica media of the common carotid artery. In that place, they were concentrated around the origin of the common trunk of each artery and were scattered below the origin along the longitudinal axis and on the opposite side of the origin. The serotonin-immunoreactive cells distributed around and in the arteries may be involved in the control of blood flow and may have chemoreceptive properties. PMID- 2195920 TI - Lyme disease. AB - Lyme disease is a complex multisystem disorder recognized on six continents that is epidemic in some parts of the world during spring, summer, and fall seasons. It is an infectious disease caused by a spirochete, B. burgdorferi, which is transmitted chiefly by I. dammini and pacificus ticks in the United States and I. ricinis in Europe. It is a disease with early and late cutaneous manifestations plus involvement of the nervous system, heart, eye, and joints in variable combinations. Diagnosis is based on patient contact with an endemic area, one or more characteristic clinical features, particularly erythema migrans rash, and a positive serologic test for B. burgdorferi infection in the majority of cases with illness greater than 4 to 6 weeks' duration. Although infection is the primary cause, immune mechanisms almost certainly play a synergistic role in some manifestations during late stages. Prompt diagnosis and treatment are important for full recovery. Therapy with doxycycline or amoxicillin is effective in the earliest stages but serious late complications require high doses of intravenous penicillin or ceftriaxone. Some sequelae respond well to antibiotic therapy while others such as chronic arthritis or advanced central nervous system disease may not. Anti-B. burgdorferi antibodies appear to be protective in certain experimental studies but data are limited and inconclusive in humans. PMID- 2195921 TI - Effect of low-dose troleandomycin on glucocorticoid pharmacokinetics and airway hyperresponsiveness in severely asthmatic children. AB - Fifteen hospitalized asthmatic children (8 to 18 years old) completed a 2-week randomized, parallel, double-blind placebo-controlled comparison of combination methylprednisolone and placebo troleandomycin, prednisone and troleandomycin (P TAO) or methylprednisolone-TAO (MPn-TAO). Troleandomycin (250 mg once daily or every other day) and glucocorticoid doses were reduced by a standard protocol. Symptom scores, blood chemistries, pulmonary function tests, airway response to methacholine, and glucocorticoid pharmacokinetics were compared. In each group, a steroid dose reduction of 50% was achieved without a deterioration in symptom scores. Methacholine response was unchanged in all five on methylprednisolone alone, but decreased 3-fold to 30-fold in two of five on combination P-TAO, and four of five on combination MPn-TAO. Troleandomycin decreased MPn clearance by an average of 62% but did not alter prednisolone clearance. Low-dose TAO combined with MPn has a significant effect on methylprednisolone clearance in children, an effect equivalent to that reported with higher dose TAO (1000 mg/d) therapy. In addition, this preliminary study suggests that TAO may decrease bronchial hyperresponsiveness to methacholine in severely asthmatic children. PMID- 2195922 TI - Open study of hydroxychloroquine in the treatment of severe symptomatic or corticosteroid-dependent asthma. AB - To examine the possible usefulness of the immunomodulating antiinflammatory drug, hydroxychloroquine (HCQ), in the treatment of asthma, we studied the response of 11 asthmatics, four severe symptomatic nonsteroid dependent and seven steroid dependent, in an open label 28 week trial at doses of 300 to 400 mg/d. Evaluation measures included daily symptom diary scores of six symptoms, subjective global evaluation, spirometric flow studies, and cumulative monthly steroid dosages. Baseline plasma theophylline and IgE levels were also obtained and compared with values during treatment. For the group as whole, mean FVC and FEV1 increased 10% and 17% respectively (P less than .01) and the mean of each of six symptom scores declined significantly (P less than .05). Among the nonsteroid-dependent asthmatics, the mean FVC and FEV1 rose 19% and 32% respectively (P less than .05) and mean symptom scores for five of six symptoms declined from baseline (P less than .05). Among the steroid-dependent patients, cumulative mean monthly steroid dosage required decreased 50% from 383 mg at entry to 191 mg at week 28 (P less than .01), mean FVC and FEV1 increased by 7% and 9%, although neither of these changes achieved significance, and two of six symptom scores improved (P less than .05). Comparison of pretreatment IgE levels to levels during treatment in ten patients demonstrated a fall from a mean of 645 to 339 IU/mL (P less than .05). Adverse reactions to HCQ were infrequent and did not require discontinuing therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2195923 TI - Allergic contact dermatitis to nickel in children with atopic dermatitis. AB - We report two atopic boys with allergic contact dermatitis to nickel. Both children had early onset of atopic dermatitis and subsequently presented with infraumbilical dermatitis corresponding to the site of contact with metal snaps. A positive patch test response to 2.5% nickel sulfate in petrolatum was observed in both boys. Allergic contact dermatitis in patients with atopic dermatitis is not uncommon and probably occurs more often than recognized. PMID- 2195924 TI - [Proteins, genes and early diagnosis of Alzheimer's disease]. AB - Proteic (neuritic plaques, amyloid substances...) and genetic characteristics of Alzheimer's disease are reviewed. An infectious origin appears unlikely. After production of specific antibodies, the reported abnormal Tau proteins might represent peripheral markers of the disease. Changes in olfactory neurons, accessible for biopsy specimens, might give rise to new biological diagnosis of Alzheimer's disease. PMID- 2195925 TI - Methods of theophylline assay and therapeutic monitoring of this drug. AB - The purpose of this article is to review various analytical methods of monitoring plasma theophylline. This article was investigated by the "Drug Commission" of SFBC (Societe Francaise de Biologie Clinique). The primary objective is to provide the "know-how", particular for this analysis, which allows the choice between various analytical methods available: immunochemical or physiochemical ones. The techniques described are not necessarily the best, they are approved and tested methods which are the most frequently used in routine practice. The proposed immunochemical methods are: absorption spectroscopy methods: Enzyme ImmunoAssay (EIA), Enzyme Multiplied ImmunoAssay Technique (EMIT); Reflectance spectroscopy method: Apoenzyme Reactivation Immunoassay System (ARIS); Fluorometry spectroscopy method: Substrate Labeled FluoroImmunoAssay (SLFIA); Fluorometry spectroscopy on solid base; Polarization fluorescence spectroscopy ImmunoAssay (FPIA); Turbidimetric measurements: Particle Enhanced Turbidimetric Inhibition ImmunoAssay (PETINIA); Nephelometric measurement: Nephelometric Inhibition ImmunoAssay (NIIA). And the proposed physicochemical methods are: High Performance Liquid Chromatography (HPLC), Gas Chromatography (GC). The second objective is a review of pharmacological properties of theophylline, necessary for a good understanding of therapeutic drug monitoring: intestinal resorption, distribution, metabolism and elimination, drug interactions, dose/response relationship, physiopathological variations and proposed "predictive" "theophylline test". The authors conclude that because of the multiplicity of methodologies used in theophylline therapeutic monitoring the choice of one of them is not easy. The best way to compare different techniques available would be the use of a "reference material" for theophylline monitoring and a quality control network between different clinical pharmacological laboratories. PMID- 2195926 TI - [Immunologic aging. Effect of denutrition]. AB - Ageing leads to decrease of immune functions. The T lymphocyte is more susceptible to ageing than the B lymphocyte for which in vitro functions are almost preserved. All functions of cell mediated immunity are decreased in elderly. T lymphocyte are less mature, present decreased T helper and T suppressive functions, decreased T proliferative ability responses to stimuli and lower interleukin synthesis. T dependent antibody responses are also decreased: primary responses are diminished and secondary responses less specific. Nevertheless in healthy elderly such immune deficiency remains minor. Underdiminution whatever it concerns (mostly proteins but also vitamin or trace elements) also leads to immunodeficiency. When it occurs in aged individuals, undernutrition rapidly induces a profound immunodeficit. Prevention of prompt treatment of all undernutrition states is a major concern in geriatrics. PMID- 2195927 TI - Serum and tissue cage fluid concentrations of ciprofloxacin after oral administration of the drug to healthy dogs. AB - Ciprofloxacin, a fluoroquinolone antimicrobial agent, was administered orally to 4 healthy dogs at dosage of approximately 11 and 23 mg/kg of body weight, every 12 hours for 4 days, with a 4-week interval between dosing regimens. Serum and tissue cage fluid (TCF) concentrations of ciprofloxacin were measured after the first and seventh dose of each dosing regimen. The peak concentration was greatest in the serum after multiple doses of 23 mg/kg (mean +/- SEM; 5.68 +/- 0.54 micrograms/ml) and least in the TCF after a single dose of 11 mg/kg (0.43 +/ 0.54 micrograms/ml). The time to peak concentration was not influenced by multiple dosing or drug dose, but was longer for TCF (6.41 +/- 0.52 hour) than for serum (1.53 +/- 0.52 hour). Accumulation of ciprofloxacin was reflected by the area under the concentration curve from 0 to 12 hours after administration (AUC0----12). The AUC0----12 was greatest in the serum after multiple doses of 23 mg/kg (31.95 +/- 1.90 micrograms.h/ml) and least in the TCF after a single dose of 11 mg/kg (3.87 +/- 1.90 micrograms.h/ml). The elimination half-life was not influenced by multiple dosing or dose concentration, but was greater for TCF (14.59 +/- 1.91 hours) than for serum (5.14 +/- 1.91 hours). The percentage of TCF penetration (AUCTCF/AUCserum) was greater after multiple doses (95.76 +/- 6.79%) than after a single dose (55.55 +/- 6.79%) and was not different between doses of 11 and 23 mg/kg. Both dosing regimens of ciprofloxacin resulted in continuous serum and TCF concentrations greater than 90% of the minimal inhibitory concentration for the aerobic and facultative anaerobic clinical isolates tested, including Pseudomonas aeruginosa. PMID- 2195928 TI - The use of stories in moral development. New psychological reasons for an old education method. AB - Contemporary approaches to moral development and moral education emphasize propositional thinking and verbal discussion of abstract moral dilemmas. In contrast, this article proposes that narratives (stories) are a central factor in a person's moral development. Support for this position comes from recent theoretical contributions of Bruner, Sarbin, Spence, Tulving, and others, who have emphasized narrative thought as a major form of cognition that is qualitatively different from abstract propositional or scientific thinking. In addition, over the last 10 to 20 years psychologists investigating and conceptualizing moral development have come to emphasize such processes as empathy (Hoffman), caring and commitment (Gilligan), interpersonal interaction (Haan), personal character and personality (Coles; Hogan; Staub; Rushton). It is proposed that narratives and narrative thinking are especially involved in how these processes lead to moral development and therefore that narrative should be rehabilitated as a valuable part of moral education. PMID- 2195929 TI - Treatment of steroid-induced osteopenia with calcitonin in corticosteroid dependent asthma. A one-year follow-up study. AB - Sixty-two steroid-dependent asthmatics who had not received any form of treatment to prevent bone loss were studied during a 12-month period. Patients were randomly divided into two groups. Thirty-one patients were treated with 1 g of elemental calcium taken daily plus 100 IU of salmon calcitonin every other day, administered subcutaneously; the remaining 31 patients received only calcium supplementation. In the calcitonin group, 11 patients dropped out of the study because of severe side effects (seven patients), lack of compliance (three patients), and exacerbation of asthma (one patient). The 20 patients who completed the 12-month follow-up period were analyzed and compared with 20 sex matched patients from the control group. At one year, bone mineral density (BMD) had increased in the calcitonin group by a mean of 4% (p less than or equal to 0.001), whereas in the control group BMD had decreased by 2.5% (p less than or equal to 0.05). Parameters of bone remodeling (alkaline phosphatase and osteocalcin) decreased significantly in the calcitonin-treated group but not in the control group. Our findings show that calcitonin 100 IU, given three times/wk, is an effective drug in the treatment of steroid-induced osteopenia. Side effects, however, are frequent and cause a high degree of dropout from therapy. These findings suggest that further studies should be carried out with lower doses of calcitonin or by other better tolerated forms of delivery such as in a nasal spray. PMID- 2195930 TI - Elevated levels of leukotriene C4 in bronchoalveolar lavage fluid from atopic asthmatics after endobronchial allergen challenge. AB - Sulfidopeptide leukotrienes have been implicated in the pathogenesis of asthma because of their ability to induce bronchospasm, airways hyperreactivity, and increased mucus production. In the present study, the leukotrienes (LT) C4, D4, and E4 were measured in bronchoalveolar lavage fluid (BALF) before and 5 min after endobronchial allergen challenge in four subject groups: nonatopic nonasthmatic, nonatopic asthmatic, atopic nonasthmatic, and atopic asthmatic. As determined by high performance liquid chromatography (HPLC), after allergen challenge, the predominant sulfidopeptide leukotriene found in BALF from atopic asthmatics was LTC4. Smaller amounts of LTD4 and LTE4 were detectable. The baseline level of leukotrienes in the atopic asthmatics was 64 +/- 18 pg/ml, with measurable levels being found in nine of 11 samples. Atopic nonasthmatics had measurable levels in only one of seven baseline samples, whereas five of six nonatopic subjects had undetectable levels. Allergen challenge in atopic asthmatics resulted in significant increases in LTC4 over prechallenge levels (64 +/- 18 to 616 +/- 193 pg/ml) (p less than 0.01) and over levels in the three control groups after challenge (p = 0.0297). The atopic nonasthmatic group also had detectable leukotriene levels after allergen challenge (88 +/- 32 pg/ml), whereas leukotrienes remained undetectable in five of the six nonatopic samples. For comparison, histamine and the prostanoids prostaglandin D2 (PGD2) and thromboxane B2 (TxB2) were also measured in BALF. The levels of all three of these mediators increased in BALF from atopic asthmatics after allergen challenge. After allergen challenge, the best correlation was found between the levels in BALF for the prostanoids PGD2 and TxB2 (r = 0.88).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2195931 TI - Preventive effects of indomethacin on diaphragmatic contractile alterations in endotoxemic rats. AB - We evaluated the effects of a sublethal Escherichia coli endotoxemia with and without concomitant administration of indomethacin on diaphragmatic strength in an in vivo rat model. Ninety-six rats were inoculated subcutaneously on two successive days with 0.3 and 0.6 mg/100 g body weight of E. coli lipopolysaccharide, respectively (E animals, n = 64), or saline (C group, n = 32). E animals were divided into two groups based on subcutaneous administration of endotoxin alone (E group, n = 32) or endotoxin plus indomethacin (2.5 mg/kg body weight/day) (EI group, n = 32). Diaphragmatic strength was evaluated in 14 animals from each group 2 days after the first endotoxin or saline administration. Diaphragmatic strength was assessed by measuring the transdiaphragmatic pressure (Pdi) during electrical stimulation of the phrenic nerves at different frequencies (0.5, 10, 20, 30, 50, and 100 Hz). Lung histologic examination and measurements of lung weights were performed 1 and 2 days after the first endotoxin or saline administration in nine animals of each group each day. A slight increase in the number of neutrophils without alveolar septal thickening and alveolar edema was observed in the lungs of endotoxin inoculated animals. No differences in the lung weight to body weight ratio nor in the dry to wet weight ratio of the lungs were noted between C, E, and EI groups. Diaphragmatic weight was not different in the three groups, whereas the weights of the extensor digitorum longus, tibialis anterior, and soleus muscles were significantly reduced in E compared with C and EI animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2195932 TI - Antibasement membrane antibody disease without clinical evidence of renal disease. AB - A 20-yr-old man is described with the rare presentation of antibasement membrane antibody (ABMA) disease confirmed on renal biopsy, but with normal renal function and urinary sediment. This distinct subgroup of ABMA appears to have an excellent prognosis. The relevant literature is reviewed and summarized. PMID- 2195933 TI - Lymphocyte recruitment to the lung. AB - Lymphocyte recruitment in lymphoid tissues and inflammatory sites occurs in response to two events. The first is adherence of lymphocytes to specialized molecules expressed on the surface of appropriately stimulated vascular endothelial cells known as vascular addressins. The interaction occurs via specialized lymphocyte surface molecules known as homing receptors. There is considerable diversity among these molecules. At least three, and possibly four, different addressin-homing receptor pairs exist, regulating entry into peripheral lymph nodes, gut lymphoid tissue, BALT and intrathoracic lymphoid tissue, and inflamed synovium. Vascular addressins are expressed by specialized endothelial cells known as HEV. HEV are not found in normal lung parenchyma but may be induced to appear during an immune response. The mechanism for induction of HEV is unknown, although it may involve the action of inflammatory cytokines. It is not known whether separate endothelial cells exist with a propensity to develop into HEV or if any endothelial cells will develop into HEV if stimulated in the proper manner. Other accessory, lymphocyte-endothelium adhesion molecule pairs have been described, including LFA-1-ICAM-1 and CD4-HLA-DR. These molecules are induced by exposure of the endothelium to inflammatory cytokines, chiefly IFN gamma. Thus, local humoral influences present during inflammation can alter the possibility of lymphocyte traffic through the endothelium by regulating the presence of lymphocyte adherence molecules. These processes have been documented to occur in the lung in normal homeostasis (e.g., BALT) and in disease (e.g., immunization with SRBC). After adherence, lymphocytes exit the circulation via amoeboid motility. This motility can be altered and enhanced through chemoattractant substances that act via surface receptors. The biochemical basis of cell motility is not entirely clear but appears to involve a link between the second messengers of receptor signaling and changes in the cytoskeleton, particularly actin filaments and microtubules. Like fibroblasts and smooth muscle cells, lymphocytes appear to respond to a number of "mitoattractants," substances that cause cell cycle entry and/or progression as well as enhanced motility. This relationship illustrates the integral relationship between cell motility and proliferation and suggests that the process of cell recruitment might also prime the recruitment cells to become activated to proliferate and perform effector function. Studies of lymphocyte-mediated lung disease confirm that antigen specific as well as antigen-nonspecific lymphocytes are selectively recruited to the lung from the circulation during an inflammatory reaction in the lung.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2195934 TI - A controlled trial of colchicine to reduce the elastase load in the lungs of cigarette smokers with chronic obstructive pulmonary disease. AB - Current data suggest that emphysema in smokers is caused at least in part by the unrestrained action of neutrophil elastase on pulmonary tissues. Since colchicine reduces the secretion of enzymes from stimulated neutrophils, we designed a clinical trial to determine if colchicine could reduce the elastase load in the lungs or several putative indicators of elastin destruction. We carried out a prospective, double-blind, randomized, and placebo-controlled clinical trial. Outpatients seeking treatment for chronic obstructive pulmonary disease at the University of Texas Health Center at Tyler who met specific criteria were recruited into the study. A group of 46 cigarette smokers between 45 and 75 yr of age with chronic obstructive pulmonary disease (COPD) were studied. Colchicine or placebo was given orally in disguised capsules, 0.6 mg three times per day. Volunteers were placed on a baseline bronchodilator regimen of Theodur orally and albuterol by inhalation. Blood, urine, and bronchoalveolar lavage fluids were obtained after 1 wk of stabilization. The patients were then randomized and treated for 14 days with colchicine, and the measurements were repeated. Modifications in plasma elastin peptides and neutrophil elastase-generated fibrinopeptide A, urinary desmosines, and bronchoalveolar lavage fluid neutrophils or neutrophil elastase were the indicators of success or failure of the treatment. Pre- and posttreatment measurements in each patient and the difference between colchicine-treated and placebo-treated groups were compared. There were no statistically significant differences in either of the two types of analyses in any of the variables. We conclude that variables related to elastase load in the lungs were not modified by colchicine treatment. If a drug can be identified that is successful in modifying one of these variables, it would then have to be tested in a large-scale clinical trial in which the rate of decline in the FEV1.0 or mortality would be measured. The data presented here may provide useful information about the variability of key measurements of elastase load in the lungs and the breakdown of elastin and may aid investigators in designing similar trials in the future. PMID- 2195935 TI - Urinary uric acid:creatinine ratio, serum erythropoietin, and blood 2,3 diphosphoglycerate in patients with obstructive sleep apnea. AB - A noninvasive, inexpensive method of excluding significant sleep-associated hypoxemia would be desirable for patients being investigated and treated for obstructive sleep apnea (OSA). Sixty-eight such patients provided specimens before and after sleep studies for estimation of urinary uric acid:creatinine ratio (UA:Cr), serum erythropoietin (EPO), and blood 2,3-diphosphoglycerate (2,3 DPG). Mean (SD) morning 2,3-DPG was higher in 26 patients with overnight hypoxemia than in 42 normoxemic patients (2.54 [0.46] versus 2.24 [0.44] mmol/L; p = 0.01). Neither overnight change nor absolute values of serum EPO or urinary UA:Cr were significantly different between hypoxemic and normoxemic groups. There was a diurnal variation in serum EPO in normoxemic patients (P.M. EPO = 14.8 [7.1] mU/ml; A.M. EPO = 10.7 [7.1] mU/ml; p less than 0.05) but not in hypoxemic patients. Eighteen hypoxemic patients were restudied after using nasal continuous positive airway pressure (nCPAP) for at least 4 wk. Seven normoxemic patients not using nCPAP were restudied after a similar time. There were no significant differences between pretreatment and posttreatment nights in absolute values or percentage overnight change of blood 2,3-DPG or serum EPO in either group. In the hypoxemic (nCPAP) group, overnight change in urinary UA:Cr was lower on the second night (p = 0.04); there was no significant change in the control group. We conclude that although urinary UA:Cr, serum EPO, and 2,3-DPG may be physiologically related to hypoxemia, none of these measures can be used to predict accurately the presence of moderate nocturnal hypoxemia in patients with OSA or in monitoring the effect of their therapy. PMID- 2195936 TI - Twenty-four hour lung function in adult patients with asthma. Chronoptimized theophylline therapy once-daily dosing in the evening versus conventional twice daily dosing. AB - Many patients with asthma experience a worsening of symptoms at night and in the early morning, resulting in sleep disruption and possibly altered daily performance. A bronchodilator agent that exerts its maximal effect overnight to control nocturnal symptoms, without a worsening of the disease during the daytime, should improve the treatment of asthma. This investigation examined the efficacy and kinetics of a new chronotherapeutically optimized, sustained-release theophylline formulation administered once daily (OD) in the evening at 8:00 P.M. in comparison with a conventional sustained-release theophylline administered twice daily (TD) at 8:00 A.M. and at 8:00 P.M. in the same dose. After a theophylline clearance study to substantiate normal or slow metabolism of the drug, a dose-titration period, and a 24-h baseline spirometric study of patients not receiving any medication, participants were randomized to 7-day treatment phases with either OD or TD. Each outpatient segment of 6 days of OD and TD was followed by a 24-h inpatient study on Day 7 when serum drug level and spirometric (PEF, FEV1, and FEF25-75) parameters were obtained every 2 h. The conventional TD treatment was associated with a constant serum theophylline level over the 24 h. In contrast, the OD treatment was associated with larger peak-to-trough drug level fluctuation, with higher levels produced overnight and lower ones in the evening at the end of the dosing interval. Compared with the baseline references, both OD and TD significantly improved airflow over the entire 24 h and to a comparable extent. However, between 2:00 and 6:00 A.M., PEF and FEV1 were significantly greater with OD than with TD. The improvement in PEF and FEV1 at this time, because of OD, was correlated with the serum theophylline level. This was not the case for TD. The improvement in airflow over baseline values between 2:00 and 6:00 P.M. was not correlated with theophylline level with either treatment regime. Overall, the chronotherapeutically conceptualized OD treatment administered in the evening resulted in better airflow levels overnight than did the TD regime without loss of airflow in the afternoon. PMID- 2195937 TI - Inflammatory cells and eosinophilic activity in asthmatics investigated by bronchoalveolar lavage. The effects of antiasthmatic treatment with budesonide or terbutaline. AB - We investigated the constituents of bronchoalveolar lavage (BAL) regarding cell profiles and released eosinophilic cationic protein (ECP) in 11 patients treated occasionally with inhaled bronchodilators (Group A) and 11 patients treated regularly with inhaled corticosteroids (Group B). A normal, healthy control group of 12 subjects was also recruited. Compared with Group A, Group B had a reduced recovery percentage of infused volume (p less than 0.05) and total cell number (p less than 0.01). Compared with the control group, there was a significant increase in the percentage of eosinophils (p less than 0.05) in both groups of asthmatics. In Group A there was also a significant increase in mast cells (p less than 0.05), serum-ECP (p less than 0.05), and BAL-ECP (p less than 0.001). No correlations between any of the cell variables and the level of airway responsiveness measured as PC20 histamine were found in any group. Group A patients were investigated twice--before and after 4 wk of randomly allocated treatment with either a regular beta-2-receptor agonist (terbutaline 250 micrograms, two puffs four times a day) or a regularly inhaled corticosteroid (budesonide 200 micrograms twice a day). The BAL differential cell counts were similar and not significantly affected by either treatment. However, BAL-ECP levels were decreased by budesonide treatment (p less than 0.05). ECP levels in serum and BAL were significantly correlated (p less than 0.05 to 0.001). The eosinophilic cell involvement in asthma is further emphasized by this study but the increase in numbers of eosinophils seems less important than their activity, here measured as release of one degranulation product, ECP. To suppress disease activity, repeated long-term treatment is important, but clear preference for either treatment cannot be given on the basis of our present results. PMID- 2195938 TI - "A glass a day keeps the doctor...". PMID- 2195939 TI - [Lengthening of the extremities in osteochondrodysplasias]. PMID- 2195940 TI - [Platelet immunoglobulins and complement in idiopathic thrombocytopenic purpura. Specificity to the IIb/IIIa membrane complex]. AB - Platelet-associated IgG, IgM and C3c was studied by an enzyme-linked immunosorbent assay (ELISA) procedure using polystyrene microter plates and solubilize platelets. At the time of investigation patients fell into the following disease categories: 24 chronic ITP, 10 acute ITP and 11 ITP in remission (normal platelet counts). A significant elevation of platelet IgG was found in acute and chronic ITP. The C3c was increased in acute categories and normal in the others. There was not significant difference in the immunoglobulins and complement values between ITP in remission and normal donors. The platelet specificity of IgG and IgM antibodies to IIb/IIIa membrane complex was positive in 20% from chronic ITP and in none from acute. It is concluded that an elevated platelet immunoglobulins or complement is usefull for ITP diagnosis but the difference between acute and chronic categories only is possible in some cases by the antibodies specificity. PMID- 2195941 TI - [Clinical evaluation of glycohemoglobin and serum glycoproteins using affinity chromatography in children with type I diabetes mellitus]. AB - We measured in 67 diabetic and 40 non-diabetic children glycosylated haemoglobin levels by both affinity chromatography (Gly Hb) and cation exchange chromatography (Hb A1), glycosylated plasma proteins by affinity chromatography (Gly PP) and glycosylated serum proteins by the colorimetric method of thiobarbituric acid (PSG). There was in the diabetic children a significant linear correlation between these four determinations, as well as between them and the values in mean glycaemias and mean glycosurias. The average Hb A1 over a 20 month observation period was 11.7%; the mean Gly Hb, 12.7%; the mean Gly PP, 5.3%, and the average PSG, 0.77 nmol HMF/mg protein. Glycohaemoglobin levels were within the normal range in only 5% of the cases. About 25% of the diabetic children showed a bad therapeutic compliance, which progressively deteriorated when age and duration of disease increased. Daily insulin requirements and glycosylated haemoglobin levels were significantly higher in diabetic girls than boys, but these differences between sexes did not exist where concentration of glycosylated proteins was concerned. Values in glycohaemoglobin and glycoproteins increased together with age, duration of disease and insulin requirements, existing an inverse relationship with both duration of clinical remission period and socioeconomic level. Motivation, dietetic obedience and, above all, self control compliance were the variables that exerted the greatest influence on glycohaemoglobin and glycoprotein levels. PMID- 2195943 TI - [Prenatal diagnosis of a splenic cyst]. PMID- 2195942 TI - [Ultrasonic diagnosis of neuroblastoma]. AB - Neuroblastoma is one of the most frequent tumors in childhood. Suprarenal area is its main abdominal location, appearing in lesser proportion in paravertebral ganglionar chains. Its prediction depends principally on the age of the patient and the pathological stage. US are the best method for its diagnosis. Its most frequent appearance is as an hyperechogenic heterogeneous mass with calcifications inside. In evaluation tumoral extension, other complementary methods such as CT and MRI should be used. PMID- 2195944 TI - [Fryns syndrome. Report of the first case in Spain]. PMID- 2195945 TI - [Role of T lymphocytes in systemic lupus erythematosus]. AB - In very active systemic lupus erythematosus (SLE), the serum levels of interleukin-2 (IL-2) are increased, indicating activation of T lymphocytes in the organism. The peripheral blood, however, contains T cells with a strongly reduced functional capacity, which results from a post-activation/refractory state; this hypofunction is reversible. Thus, the activity of the T lymphocytes in the circulating pool is the "mirror image" of the activity of these cells at the level of the whole organism. The B lymphocyte hyperactivity in SLE is T dependent. A highly specific mechanism is involved in the activation of the B cells producing anti-native DNA antibodies. The investigation of lymphocyte functions enables one to follow the effect of immunosuppressive therapy. PMID- 2195946 TI - [Contribution of murine models of spontaneous lupus to the analysis of genetic factors in human disease]. AB - Genetic factors contribute to the expression of human systemic lupus erythematosus (SLE): they appear to be complex and are difficult to study in man. Most advances have been made as a result of studies of spontaneous murine models of SLE, either by conventional genetics or molecular biology. The former demonstrated that no single or simple genetic explanation of the disease is likely and that the immune manifestations are multigenic. Molecular biology techniques suggest that disease-associated genes probably lie within the major histocompatibility complex (MHC) of NZW mice and seem to be genes coding for MHC class II antigens. Such an analysis of genes encoding elements involved in immune system functions (e.g., immunoglobulins, T cell antigen and MHC antigen receptors) provides valuable information concerning the role(s) of genetic factors leading to SLE. PMID- 2195947 TI - [Pathogenic role of antinuclear antibodies in lupus disease]. AB - The majority of anti-nuclear antibodies do not have a proven pathogenic role in systemic lupus erythematosus (SLE). The pathogenicity of native anti-DNA antibodies, suggested by clinical data, is difficult to confirm. It is linked to several factors: isotype and avidity of these antibodies, affinity for DNA, size of immune complexes. DNA, anti-DNA antibodies and cross-reactive anti-DNA idiotypes (16/6) have been isolated from human and NZB mouse glomeruli. Moreover, DNA has a particular affinity for the glomerular membrane due to its cross reactivity with some constituents of this membrane. Anti-SSA (Ro) antibodies may play a role in some cases of nephropathy in SLE and participate in photosensitization. They are associated with neonatal lupus, with some cases of fetal death in black women and with the atrioventricular heart block. However, factors other than these antibodies are needed to induce such lesions. Anti-U1 RNP antibodies do not protect against kidney involvement in SLE; however, they can decrease suppressive function by penetrating into suppressor T cells. Anti-Sm antibodies may have particular immunoregulation properties. Some antinuclear antibodies may at least in part, be responsible for the lesions in SLE, in conjunction with other still-unknown factors. PMID- 2195948 TI - [Evaluation of the clinical activity of systemic lupus erythematosus]. AB - It is difficult to measure clinical disease activity in systemic lupus erythematosus because many organs can be involved simultaneously and the corresponding symptoms are not easy to quantify. Disease activity is poorly defined and there is no consensus on what disease activity means or how it should be measured. More than 60 systems have been devised but none of them is commonly used because they do not have the 3 characteristics necessary for such a tool: validity, reliability and sensitivity. Three recent systems, BILAG (British Isles Lupus Assessment Group), SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) and SLAM (Systemic Lupus Activity Measures) are very valid. Comparisons of their reproducibility are in progress; however, more information is needed concerning their sensitivity and the feasibility of making these systems easy to manage for physicians. PMID- 2195949 TI - [Have lupus characteristics changed?]. AB - The features of lupus have been changing for 30 years. The aim of this study was to determine the main modifications and to search for the possible causes. Lupus epidemiology, the clinical symptoms and the prognostic subsets were investigated. The rising incidence of lupus closely paralleled improvements in diagnostic techniques (LE cell testing, anti-nuclear antibodies) but has since remained stable. The prevalence progressively increased over this time, but this evolution is associated with better detection of benign subsets and improvement in the management of the disease and its complications. More sensitive serological methods have attributed new symptoms to lupus, revealing that some forms are benign. Survival has been improving and infection has become the primary cause of death. Opportunistic infections in lupus are increasing, however the majority of them remain undiagnosed until the autopsy. PMID- 2195950 TI - [Protein-losing enteropathy and systemic lupus erythematosus]. PMID- 2195951 TI - [Rhabdomyolysis following insulin therapy in hyperosmolar syndrome]. PMID- 2195952 TI - [Radiation-induced cancer after treatment of seminoma. Apropos of a case of non Hodgkin's lymphoma occurring 18 years after cobalt therapy]. PMID- 2195953 TI - [Necrobiotic xanthogranulomatosis disclosing multiple myeloma]. PMID- 2195955 TI - Examination under anesthesia. AB - Examination under anesthesia, particularly in children, is a common practice in ophthalmology. It may yield valuable information as to the cause and management regimen of the condition under study. The proper equipment should be available to the clinician to expedite the examination. Rapid and useful information thus obtained can justify the risk and expense incurred when this modality is used. Efficient use of the equipment is essential to yield the best examination. PMID- 2195954 TI - Presumed choroidal metastasis of Merkel cell carcinoma. AB - Merkel cell carcinoma is a rare skin tumor of neural crest origin and is part of the amine precursor uptake and decarboxylase system. It typically occurs on the face of elderly people. Distant metastasis is almost uniformly fatal. Choroidal metastasis, to our knowledge, has not been described. We report a patient with Merkel cell carcinoma who had a synchronous solid choroidal tumor and a biopsy proven brain metastasis. Our 56-year-old patient presented with a rapidly growing, violaceous preauricular skin tumor. Computed tomography of the head disclosed incidental brain and choroidal tumors. Light and electron microscopy of biopsy specimens of both the skin and the brain lesions showed Merkel cell carcinoma. Ophthalmoscopy, fluorescein angiography, and A and B echography revealed a solid choroidal mass. The brain and skin tumors responded well to irradiation. A radioactive episcleral plaque was applied subsequently to the choroidal tumor. All tumors regressed, and the patient was doing well 28 months later. To our knowledge this is the first case of presumed choroidal metastasis of Merkel cell carcinoma. PMID- 2195956 TI - Nonclosure of pharyngeal muscle after laryngectomy. AB - A prospective study was carried out to evaluate a new technique of pharyngeal repair following laryngectomy. The purpose of this study was to see whether satisfactory healing would occur if the pharyngeal constrictors were not sutured across the closure in the pharynx. If healing proved to be satisfactory the procedure might eliminate the need for primary or secondary myotomy or pharyngeal plexus neurectomy to facilitate tracheoesophageal speech. The results indicate that healing is as good in the group who did not have muscle closure as in those who did. PMID- 2195957 TI - Ligneous conjunctivitis: an ophthalmic disease with potentially fatal tracheobronchial obstruction. Laryngeal and tracheobronchial features. AB - Ligneous conjunctivitis is a rare disease of unknown cause characterized by pseudomembranous, fibrous, woody, plaquelike deposits on the conjunctiva. The disease appears to be hereditary and/or familial. Deposits similar to those found in the eye occur in the larynx, tracheobronchial tree, nose and nasopharynx, and vagina. When these lesions occur in the larynx and tracheobronchial tree, voice change and potentially life-threatening obstruction and pulmonary disease may occur. This paper reports the findings in a child with ligneous conjunctivitis who was followed for 1 1/2 years and who had laryngeal and tracheobronchial involvement with voice change and airway obstruction. The literature is reviewed and the histopathologic findings and endoscopic findings and management of the patient are documented. Because the patient had multiple papillomata of both hands, a possible association with human papillomavirus was suspected but never confirmed. PMID- 2195958 TI - Use of the nasogastric tube after total laryngectomy: is it truly necessary? AB - The nasogastric tube has been routinely used to feed the patient during the first postoperative days after a total laryngectomy. In the last 21 years the author has performed 625 total laryngectomies without using the feeding tube. With this procedure oral feeding could be started during the third postoperative day, making the patient more comfortable and confident. In addition, the hospital stay was shortened. It was also observed that the incidence of pharyngeal fistulas (9%) was comparable to that of other reports in the literature. PMID- 2195959 TI - Laryngeal chondrosarcoma: incidence, pathology, biological behavior, and treatment. AB - Chondrosarcoma is the most common mesenchymal tumor of the larynx and approximately 200 cases have been collected in the world medical literature. It is less aggressive in the larynx than elsewhere: cervical or distant metastases are rare (8.5%), and although local recurrences are not uncommon, they are not catastrophic. A retrospective study was made on eight cases of laryngeal chondrosarcoma. Three cases had originally been diagnosed as idiopathic vocal cord paralysis, possibly because of early involvement of the cricoarytenoid joint or the distal portion of the recurrent nerve. This fact emphasizes the need for accurate laryngeal computed tomography in cases of vocal cord paralysis of unknown origin. Surgical excision is the treatment of choice for laryngeal chondrosarcoma, and conservative techniques may sometimes be appropriate. Supraglottic laryngectomy may be the technique of choice in the rare cases of epiglottic involvement. PMID- 2195960 TI - Bilateral endolymphatic hydrops in Meniere's disease: review of temporal bone autopsies. AB - The wide range in incidence rates reported for bilateral Meniere's disease results mainly from the lack of established clinical criteria for bilaterality, and from follow-ups of varying duration. In order to help determine a reasonable bilateral involvement rate, we examined histologic reports of temporal bones with endolymphatic hydrops. We reviewed the literature on temporal bone autopsies from 1938 to 1988, and selected 72 cases for histologic examination. Of the 72 cases, 67 (93%) showed endolymphatic hydrops, 2 (2.8%) showed collapse, and 3 (4.2%) showed membranous labyrinths of normal appearance. Twenty of the 67 endolymphatic hydrops cases (29.9%) displayed bilateral involvement, suggesting a rate of bilaterality in Meniere's disease of approximately 30%. PMID- 2195961 TI - Immunoglobulin E and circulating immune complexes in endolymphatic hydrops. AB - Levels of circulating immune complexes (CICs) in 59 patients with Meniere's disease and total serum immunoglobulin E (IgE) levels in a subgroup of 42 of the 59 were determined quantitatively for possible abnormalities of humoral immunity. Significant differences in average IgE levels between the 42 patients with Meniere's disease and 18 normal control subjects were not determined; however, five (11.9%) of the 42 patients were found to have obviously raised IgE levels. Elevated CIC levels were found in 19 (32.2%) of the 59 patients with Meniere's disease and in one (2.3%) of the 43 control subjects. This difference was statistically significant. The possible mechanisms of immune-mediated endolymphatic hydrops are discussed. PMID- 2195962 TI - Sensitivity and specificity of the head-shaking test for detecting vestibular system abnormalities. AB - The head-shaking nystagmus (HSN) test has been reported to be a sensitive screening test for the presence of peripheral and central vestibular system disease. Previous investigations have utilized few subjects who were drawn from well-defined patient populations. The purpose of the present investigation was twofold: first, to determine the prevalence of HSN in a large unselected population of dizzy patients seen in an otology and neurotology practice, and second, to determine the sensitivity and specificity of this evaluation in the detection of vestibular system abnormalities as reflected by results of electronystagmography and rotary chair testing. The results of the investigation have suggested that the HSN test has a 27% sensitivity and an 85% specificity. The HSN test yields an acceptable number of false positives (15%) and an unacceptably large number of false negatives (73%). PMID- 2195963 TI - Malignant transformation in a laryngeal hemangioma. AB - Laryngeal angiosarcoma is uncommon, with only 19 previously reported cases. Malignant transformation in nonirradiated hemangiomas is extremely rare, with only five equivocal cases reported, all of which occurred in the skin. We report the first documented case of malignant transformation in a laryngeal hemangioma, and review the literature. PMID- 2195964 TI - Primary lymphoplasmacytic lymphoma of the larynx: a rare localization of MALT type lymphoma. AB - Laryngoscopy carried out in a 46-year-old man revealed a left paralaryngeal tumor. The mass was entirely removed by left pharyngolaryngotomy. Microscopic study showed a diffuse malignant lymphoma of low-grade malignancy, exhibiting all the criteria of the MALT-type lymphoma: the proliferation of centrocyte-like and lymphoplasmacytic cells, lymphoepithelial lesions, and the presence of germinal centers. Primary lymphoma of the larynx is a rare condition. Most of the reported low-grade lymphomas and the pseudolymphomas probably belong to the category of MALT-type lymphoma. Remission can be obtained by surgery, radiotherapy, and polychemotherapy. PMID- 2195965 TI - Warthin's tumor. AB - Warthin's tumor, classed as a monomorphic adenoma, ranks second to pleomorphic adenoma in the incidence of benign neoplasms of the parotid gland. By embryologic and clinicopathologic definitions, it is a neoplasm of the parotid gland and its environs, including parotid lymph nodes. Histopathologic diagnosis requires an oncocytic (mitochondria-rich) epithelium and lymphoid stroma. Malignant Warthin's tumors are rare and are carcinomas arising from the ductal component, or non Hodgkin's lymphomas arising from the lymphoid tissue. PMID- 2195966 TI - [Surgical treatment of suppurative axillary hidradenitis: value of a musculocutaneous island flap of the latissimus dorsi. Apropos of 3 cases]. AB - We report our experience of the surgical management of severe, extensive, medically intractable axillary Hidradenitis suppurativa in three male patients. Under general anaesthesia, all patients underwent large, deep and full excision of the disease prone areas, i. e. zones of apocrine sweat gland distribution and not only of the skin involved at the time of surgery, for the best possible prevention of recurrence. The operation was bilateral in two patients and unilateral in one. In all cases closure was achieved using the latissimus dorsi flap technique. In the two patients with bilateral lesions surgery was carried out in two steps at about two months' interval. At present, after a follow-up of about two years, none of the patients have relapsed and their shoulder mobility is perfectly preserved with a normal abduction allowed by the total absence of axillary scar contracture. The latissimus dorsi flap technique consists of transplanting into the recipient's axillary defect the pedicellated lateral margin of the latissimus dorsi muscle with (2 patients) or without (1 patient) a cover of attached skin palette vascularized by the underlying muscle tissue. Mainly used hitherto for reconstructive mammary surgery, this technique perfectly fits axillary diseases, such as Hidradenitis suppurativa, which can only be cured by creating wide surgical skin defects. It is particularly reliable: covering of the defect is easy and the immediate muscle interposition effectively protects the otherwise widely exposed neurovascular pedicle. The need for a skin palette cover associated with the latissimus dorsi flap is discussed. PMID- 2195967 TI - [Adult Langerhans cell histiocytosis with cutaneous involvement. Review]. PMID- 2195968 TI - [Current use of thalidomide]. PMID- 2195969 TI - [Epidemiology of meningococcal infections and principles for the prevention of secondary cases]. AB - The incidence of meningococcal infections undergoes secular variations with modifications in the distribution of identified serotypes. Rhinopharyngeal carriage of meningococci, common in the community, is the natural means of immunization. Prevalence of this carriage varies across age groups and communities, as well as according to whether or not cases are present in the community under study. Identified factors that promote transmission of the bacteria include crowded living conditions, poor socioeconomic conditions, and, more controversially, respiratory tract viral infections. Development of meningococcal infection usually occurs within seven days of onset of carriage. Secondary cases account for approximately 3% of meningococcal infections in France. The risk of development of secondary cases is increased in subjects sharing the patient's home or exposed to his or her rhinopharyngeal secretions. Prevention of these secondary cases rests on chemoprophylaxis and immunization. The qualities of antimicrobial agents proposed for chemoprophylaxis are discussed, with special emphasis on spiramycin and rifampin which are the most widely used. This study, which rests on French epidemiologic surveillance findings and data from a review of the literature, forms the basis for new French guidelines. PMID- 2195970 TI - [Gastric teratoma in newborn children]. AB - In neonates, teratomas infrequently involve the abdomen: among 51 known cases, 39 were gastric teratomas, which account for less than 2% of all germ cell tumors in the neonatal period. Associated malformations are minor, located in the region of the tumor, and apparently less frequent than in other sites. Malignancy is exceedingly rare (a single case) and well controlled as a result of the anti tumor processes specific to the neonatal period. Gastric teratomas are diagnosed early and can be cured by tumorectomy removing a thin ring of the surrounding stomach wall. PMID- 2195971 TI - [Attachment for the aggressor: on the Stockholm syndrome in children]. PMID- 2195972 TI - [Autism in infants and young children. The value of early diagnosis]. AB - Clinical studies of early symptoms are among the most significant advances achieved during recent years in the field of autism. The first descriptions of early symptoms were retrospective and lacked precision. Autistic children are now being seen increasingly early and new insight is being gained into the initial manifestations and differences in clinical patterns. Similarly, differential diagnosis problems (borderline forms) are changing as clinicians evaluate children at younger ages. Although a definitive diagnosis is neither possible nor even desirable before the age of 18 to 24 months, detailed clinical data should be collected early. This data forms the basis for differential diagnosis and will be needed later for differentiating various clinical patterns of developmental disorders, establishing a prognosis, and monitoring therapeutic effects. In prospective longitudinal studies of autistic children, comparison of recent observations with detailed early data is essential. Early initial evaluation includes videotape recordings, assessment of cognitive functions and communication skills, and use of a scale for autistic symptoms. Using the results of evaluations of very young children, a specific semiology (communication disorders) can be developed. Several symptoms probably denote neurophysiologic and/or perceptive disorders. Primary symptoms are now being better distinguished from secondary anomalies (behavior disorders) that may be avoidable or treatable. PMID- 2195973 TI - [A cerebral abscess due to Listeria monocytogenes in a 15-month-old infant]. AB - We report a case of brain abscess due to Listeria monocytogenes in an infant. We recall that listeriosis is infrequent in pediatric patients beyond the neonatal period, that most cases occur in immunocompromised hosts, and that clinical features are non-specific in neuromeningeal forms. Management of brain abscesses is discussed. The role of the patient's general health condition seems to have a determinant influence on prognosis. PMID- 2195974 TI - [Benign paralysis of the 6th cranial nerve in children]. AB - Acquired sixth nerve palsies in infants and children that occur without fever primarily suggest a tumor or intracranial hypertension. In a few instances, the cause is benign and spontaneous recovery occurs although relapses are occasionally seen. We report seven episodes of benign sixth nerve palsy in four children aged 5 1/2 months to 8 1/2 years. An ENT infection was the precipitating factor in four of these seven episodes. Recovery consistently occurred within 4 days to 6 weeks. None of the children had residual oculomotor impairment. The various etiologic hypotheses put forward in the literature are discussed. No study provides a pathophysiologic explanation for these transient palsies. PMID- 2195975 TI - [False tendons of the left ventricle associated with vectorcardiographic changes. Preliminary study]. AB - False tendons are not simply a curiosity discovered on echocardiographic examination or at autopsy. These fibromuscular structures might be connective bundles which contribute to intraventricular activation. They have been implicated in the genesis of arrhythmia (extrasystole or even ventricular fibrillation) by certain authors. 26 subjects with a strictly normal vectorcardiogram (VCG) were chosen at random and 71 subjects with an abnormal VCG were selected from a large population of young, healthy subjects. Using echocardiography, a false tendon was discovered in one subject from the first group and in eight subjects in the second group. Such disproportion (1/26 versus 8/71) was quite unexpected and lends weight to the idea that the false tendon is frequently active and is capable of altering the process of intraventricular activation. The modifications might result in vectorcardiographic traces such as those occasionally observed in healthy subjects. PMID- 2195976 TI - [Efficacy and tolerability of verapamil in mild to moderate hypertension]. PMID- 2195977 TI - [The natural history of coronary disease. The role of cholesterol]. AB - The natural history of the complications of coronary heart disease has been defined by anatomicopathological and epidemiological studies, particularly the Framingham study. At the same time, research is being carried out on risk factors which play a role in the progressive development of atheromatous plaque (atherogenic factors: hypertension: hypercholesterolaemia) and those factors which lead to complications in the atheromatous plaque (aggravating or precipitating factors: smoking, thrombosis, etc.). This schematic perspective may lead to the redefinition of the strategy to adopt in fighting atherosclerotic arterial disease; a better aim will thus the taken in the fight against hypercholesterolaemia. PMID- 2195978 TI - [Hypertension in the elderly. Comparison of the efficacy and tolerability of labetalol and nifedipine. A multicenter, randomized, single-blind study]. AB - This randomized multicentre study in elderly hypertensives with two unbalanced groups (2 patients under labetalol for 1 patient under nifedipine) compared the efficacy and safety of labetalol, whose dosage could be adjusted (1, 2, then 3 tablets/day) according to blood pressure level (BP greater than or equal to 160/95 mmHg), to that of nifedipine given at its recommended dosage (2 tablets/day). The treatment period lasted 6 weeks (D42). The main judgment criteria was the rate of patients with normalized BP under treatment (SBP less than 160 and DBP less than 95 mmHg). The analysis was carried out on 170 patients, 112 labetalol and 58 nifedipine. Both groups were homogeneous when entering into the study. The only difference was a higher rate of smokers in the nifedipine group compared with labetalol's (29% vs 13%). The rate of patients with normalized BP (SBP less than 160 and DBP less than 95 mmHg) were 66% in the labetalol group and 48% in the nifedipine's (p less than 0.05). Treatment withdrawals for all causes during the study were more frequent in the nifedipine group (19%) than in the labetalol's (6%). Treatment withdrawals for adverse events occurred in 3.5% of patients in the labetalol group and in 12% of the nifedipine's. The overall adverse events rate was 9% with labetalol and 29% with nifedipine (p less than 0.001). In this comparative study in elderly hypertensives, labetalol given in a dose titration schedule proved significantly superior to nifedipine, given at recommended maximal dosage, in terms of both BP control and side effects profile.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2195979 TI - Ring chromosome 16: a new case. AB - A 46,XX,r(16) "de novo" karyotype is reported in a 4 7/12-year-old girl. In spite of the mild cranio-facial dysmorphism without visceral malformations in r(16) patients, the proband's phenotype is similar to the other four previous case reports. This could support the hypothesis of a specific "r(16) syndrome". PMID- 2195980 TI - Interstitial deletion of the short arm of chromosome 12. Report of a new patient and review of the literature. AB - In this report we describe a female neonate with 12p interstitial deletion (karyotype: 46,XX,del(12)(pter----p13.1::p11.2----cen----qter). In addition to severe psychomotor retardation, facial dysmorphism and Turner like stigmata, she presented marked hypoplasia of the external genitalia and right heart hypoplasia. Study of LDH activity showed a marked decrease of LDHB activity contrasting with an elevated LDHA. PMID- 2195981 TI - Direct duplication 16q11.1----16q13 is not associated with a typical dysmorphic syndrome. AB - In this report we present a 3-year-old girl with partial trisomy of the long arm of chromosome 16 due to a direct duplication 16q11.1----q13 (karyotype: 46, XX, dir dup(16) (pter----cen----q11.1----q13::q11.1----q13::q13----qter]. She presented moderate mental retardation and severe hyperkinetic behaviour. Slight dysmorphic stigmata but no internal anomalies were found. PMID- 2195982 TI - Diploid/tetraploid mosaicism in a stillborn infant with prune belly anomaly. AB - We report a case of a stillborn infant that presented multiple birth defects and a diploid/tetraploid mosaicism in skin fibroblasts. Clinical and cytogenetical findings are discussed and compared with those presented in previously reported cases. PMID- 2195983 TI - [A second case of (de novo) paracentric inversion of the short arm of the X chromosome]. AB - A de novo paracentric inversion of the short arm of an X chromosome (p11.2p22.1) was observed in a 17-year-old girl studied because of primary amenorrhea and a Turner phenotype. To our knowledge this is only the second case of a paracentric inversion of the X chromosome short arm reported, the first having been briefly described in 1982, in a young lady with the Turner phenotype. In spite of its balanced appearance, there is little doubt that this rearrangement is the cause of the phenotypic anomalies of the patient, probably as the result of gene(s) modification(s) at the breakpoints on the X chromosome, or because the inverted gene sequence resulted in modifications by position effect. It has become increasingly difficult to recognize obvious phenotype-genotype correlations in Turner syndrome, given the multiplicity of chromosome rearrangements--some of them quite subtle--which are associated with ovarian dysgenesis. PMID- 2195984 TI - Distal monosomy of the long arm of chromosome 6 (6q25----6qter) inherited by maternal translocation t(6q;17q) AB - Two half-sisters with distal monosomy of the long arm of chromosome 6 (q25--- qter) inherited by maternal translocation t(6q;17q) were investigated. The clinical manifestations of these patients are compared with eight cases reported in the literature for further characterization of the 6q-syndrome. The cytogenetic diagnosis of alterations involving small chromosome fragments and the different origins of this type of deletion are also discussed. PMID- 2195985 TI - Epidermal growth factor receptors in colorectal carcinoma. AB - Nineteen samples of primary colorectal carcinoma and adjacent mucosa were examined for EGFr expression using radioligand binding assays and immunohistochemical staining with the monoclonal antibody EGFR1. Radioligand binding experiments showed expression of EGFr in both tumour and mucosa in all cases. In tumour samples EGFr levels ranged between 4 and 79 fmole per mg membrane protein (Kd = 0.1-0.4 X 10(-9) M). There was no significant difference in the level of EGFr expression between tumour and mucosa overall. Immunohistochemical staining with the EGFR1 antibody was useful in localising EGFr to epithelial elements although it was less sensitive than ligand binding assays. PMID- 2195986 TI - Role of the Ha-ras (RasH) oncogene in mediating progression of the tumor cell phenotype (review). AB - Recent experimental evidence indicates that the c-Ha-ras (rasH) oncogene may be causally involved in the etiology and evolution of specific human neoplasms. In addition, cultured cells transformed by the rasH oncogene can induce both a tumorigenic and a metastatic phenotype when expressed in appropriate cultured cells. To begin to define the molecular and biochemical mechanism(s) by which the rasH oncogene induce their effects on expression of the transformed state we have employed a cloned rat embryo fibroblast (CREF) cell line. Transformation of CREF cells with wild-type 5 adenovirus (Wt) results in transformed cells which display anchorage-independence and an increased saturation density in monolayer culture, but are non-tumorigenic in both athymic nude mice and syngeneic Fischer rats. In contrast, when CREF cells are transformed with mutant type 5 adenoviruses, such as H5hrl, or the ElA transforming gene from hrl (0-4.5), tumors are induced in both nude mice and syngeneic rats. However, hrl (0-4.5)-transformed CREF cells are not metastatic following intravenous injection into the tail vein of syngeneic rats. Insertion of an activated T24 rasH oncogene or a wild-type v-rasH oncogene into CREF, wt-transformed CREF or hrl (0-4.5)-transformed CREF cells results in acquisition of a metastatic phenotype by these cells. A mutant v-rasH oncogene (mutant 116K), which is defective in GTP binding and the induction of transformation of NIH 3T3 cells, does not induce transformation in CREF cells, but it can progress wt-transformed CREF cells to a tumorigenic-non-metastatic state. Employing this model system which displays well-defined and stable stages in the tumor cell progression lineage, we have analyzed the potential role of changes in the phosphatidylinositol (PI) cycle and phospholipase A2 (PLA2) enzyme activity during progression to a tumorigenic and metastatic phenotype. An increase in PI cycle intermediates (primarily inositol triphosphate; IP3) were observed only in the wt-transformed and hrl (0-4.5)-transformed CREF cell lines transfected with the rasH oncogene. In the case of PLA2, all rasH-transformed CREF cell lines displayed increased activity. In contrast, CREF cells transformed only by Ad5 (Wt or hrl (0-4.5)) or the 116K v-rasH oncogene did not display increased PLA2 activity similar to that observed in rasH transfected cells. Since one important metabolite generated by PLA2 is arachidonic acid, which is converted into prostaglandins and leukotrienes by cyclooxygenase or lipooxygenase, respectively, the levels of prostaglandin E2 (PGE2) in the various cell lines were monitored.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2195987 TI - Comparison of in vitro drug sensitivity by inhibition of tritium release from [5 3H]-2'-deoxyuridine and a clonogenic assay. AB - In a search for a rapid and simple method to determine drug-induced cell lethality, the inhibition of tritium release from [5-3H]-2'-deoxyuridine (ITR) was compared with a standard clonogenic assay. Seven drugs were studied. After a 4 hr incubation period, [5-3H]-2'-deoxyuridine was added to cultures of human colon carcinoma cells (HCT-8) in vitro and four dose-response curves were generated for each drug by sampling the culture medium for tritiated H2O formation 4, 24, 48 and 72 hr later. These curves were compared to those obtained by a standard clonogenic assay. The ED50 values for 5 of the 7 drugs tested, methotrexate, 5-fluorouracil, doxorubicin, vincristine and cisplatin, as measured by inhibition of HCT-8 colony growth, were within 3 times the values observed with the metabolic assay. The ITR highly overestimated the cytotoxicity of 5 fluoro-2'-deoxyuridine: the irreversible inhibition of thymidylate synthase by this nucleoside resulted in an ED50 value 100-fold lower than that observed with the clonogenic assay. Opposite results were obtained with 5-fluorouridine. These data indicate that the ITR can be used to determine drug sensitivity of these cells to a host of compounds although it cannot be used indiscriminately for every antineoplastic agent as a cytotoxicity assay. PMID- 2195988 TI - Effectiveness of cis-platin and carboplatin in the chemotherapy of squamous cell carcinoma grown as multicellular spheroids. AB - We compared cis-platin (DDP) and its analogue, carboplatin (JM8, CBDCA) in their ability to inhibit spheroid growth. The activities of DDP and JM8 were also compared in an antimetabolic assay for their ability to inhibit (3H)-thymidine incorporation in multicellular tumor spheroids. The spheroids were derived from a squamous cell carcinoma cell line HN-1, originally derived from a tumor of the tongue. To produce equal levels of growth delay in spheroids, carboplatin was required at concentrations approximately 16 times that of DDP. Carboplatin also required much longer incubation periods than DDP to produce equivalent growth delay and proportions of cured spheroids. Reflecting the initial response to chemotherapy, the antimetabolic assay showed that carboplatin was required at higher concentrations and longer exposure times to produce equal inhibition of the nucleotide precursor thymidine. These findings may have implications for the clinical use of these drugs and in particular would support a role for carboplatin in the treatment of squamous cell carcinoma of the head and neck, since total free-drug exposure of patients to carboplatin may be up to 16-fold greater than with DDP, and the clinical side effects of carboplatin have been shown to be well tolerated. However, one must be cautious about applying in vitro data to clinical situations. PMID- 2195990 TI - Skin ulcers. Overview, nursing implications. PMID- 2195991 TI - Myocutaneous flaps. Surgical treatment of severe pressure ulcers. AB - Surgical treatment of pressure ulcers using the myocutaneous flap procedure is a relatively new approach for patients with spinal injuries. First, the pressure ulcers are treated conservatively; however, if they become large or infected, surgery is considered. We have performed approximately 1,500 of these surgeries in the past five years. Only 5% of the cases have developed complications. The primary complication experienced was small wound dehiscence, which we attributed to mechanical interference with wound healing. We attribute the overall success of these surgeries to the rigid protocol and interdisciplinary approach to management. PMID- 2195992 TI - Common bile duct strictures. Diagnosis, management, follow-up. PMID- 2195993 TI - Inhalation anesthetics. Comparing nitrous oxide, isoflurane, halothane, enflurane. PMID- 2195994 TI - Immunoaffinity purification of human thromboxane synthase. AB - A recently produced monoclonal antibody against human thromboxane synthase was used to purify the enzyme from platelets in a one-step procedure with good yields. The isolated protein exhibited a single band of about 58 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and contained one heme/mol. Although the visible spectrum of the oxidized enzyme displayed a peak at 418 nm like the previously isolated enzyme after dithionite reduction and CO addition, it shifted to 419 nm but not to 450 nm where only a small shoulder could be detected. Its catalytic activity was only 1-5% of the previous preparations, but with the same Km of about 10 microM and a ratio of thromboxane B2: 12 hydroxyheptadecatrienoic acid of 1:1. Studies with EPR spectrometry and inhibitors confirmed that only a minor part of the enzyme was in its native heme thiolate conformation, whereas the major part had been converted to the inactive P420 form by the elution procedure. The amino acid analysis revealed 46% hydrophobic residues. According to the sequence of 26 amino acids from the N terminus and two tryptic peptides no homology to one of the cytochrome P450 monooxygenases, or to cyclooxygenase, or to prostacyclin synthase was detected. PMID- 2195995 TI - Escherichia coli beta-hydroxydecanoyl thioester dehydrase reacts with native C10 acyl-acyl-carrier proteins of plant and bacterial origin. AB - beta-Hydroxydecanoyl-[acyl-carrier-protein] dehydrase catalyzes the essential step in the formation of unsaturated fatty acids in Escherichia coli. This reaction was characterized with native C10 acyl-acyl-carrier protein (ACP) structures in both an aqueous phase system and a substrate immobilization assay system. The dehydrase is equally active with E. coli ACP, recombinant ACP-I derived from spinach, or protein A:ACP-I fusion (acyl-thioesters). There were differences among the substrates in terms of the equilibrium product distribution. Both E. coli acyl-ACP and recombinant acyl-ACP-I as cosubstrates with beta-OH 10:0, trans-2 10:1, or cis-3 10:1 yielded about equal amounts (37 mol%) of the two monoenes regardless of the initial substrate. In contrast, the fusion acyl-ACP-I yielded only 17 mol% cis-3 10:1 with 49 mol% trans-2 10:1 present at equilibrium. These equilibrium values for native cis-3 10:1 are higher than those reported previously for the dehydrase using N-acetylcysteamine thioesters as substrates. The Km values for each beta-OH 10:0 ACP substrate were similar to each other and within the range of in vivo concentrations (5-10 microM). Dehydrase reactivity depends more on acyl chain length than ACP structure or origin and is therefore different from other branch point ACP utilizing enzymes (plant and bacterial) which discriminate according to ACP structure (D. J. Guerra, J. B. Ohlrogge, and M. Frentzen, 1986, Plant Physiol. 82, 448-453). PMID- 2195996 TI - Immunoaffinity purification of type I protein kinase C. AB - We designed a simple procedure for the purification of type I protein kinase C, using immunoaffinity chromatography with a monoclonal antibody, MC-1b, obtained by rescreening hybridoma cells available for an affinity ligand. Western blotting demonstrated that MC-1b specifically reacted with type I protein kinase C, and the enzyme molecule dissociated from MC-1b-coupled Sepharose 4B with mild eluants such as thiocyanate retained the kinase activity. A 1148-fold purification was achieved and 210 micrograms of type I protein kinase C was obtained from three rabbit brains, by means of a two-step procedure, using DEAE-cellulose and immunoaffinity chromatography. The resultant preparation was homogeneous, as indicated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis hydroxylapatite chromatography, and immunological analysis using MC-1a, MC-2a, and MC-3a. PMID- 2195997 TI - Kinetic assembling of the biologically active secondary structure for CAR, the target sequence for the Rev protein of HIV-1. AB - We predict the metastable secondary structure for the CAR (cis anti-repressor sequence) which is active in the regulation of the interaction with the Rev protein of HIV-1. We prove that the active structure sustained between nts 7364 and 7559 of the env RNA is the most probable metastable structure whose formation is kinetically governed and not thermodynamically determined. The structure is obtained by means of a Monte Carlo simulation which computes refolding events which occur as the CAR portion of the viral RNA is being assembled. Thus, the regulatory role of the secondary structure is determined as soon as the new RNA has been synthesized and it is preserved for further recognition by the Rev protein. In analogy with previous work by the author, it is shown that the destabilization by site-directed mutagenesis of the secondary structure for a non chain-specific recognition site enhances the Rev response. PMID- 2195998 TI - [Natural history of breast cancer among Japanese and Caucasian females]. AB - Breast cancer among Japanese females is characterized by its relatively low incidence and better prognosis than among Caucasian females. The annual mortality due to breast cancer among Japanese is about one-fifth that among Caucasians. Comparison of case distribution by histological type indicates that the ratio of well-differentiated carcinoma is slightly higher among Japanese, while the ratio of poorly differentiated carcinoma is slightly higher among Caucasian females. It is noteworthy that the incidence of in situ and invasive lobular carcinoma among Japanese is much lower than among Caucasian females. The age distribution shows that breast cancer is more frequent among middle-aged females in Japan, but more common among aged females in the West. Breast cancer among Japanese females shows a better prognosis than among Caucasian females as a whole, and even with equal tumor size and lymph node metastasis. It seems that postmenopausal breast cancer among Caucasian has a worse prognosis than the premenopausal one, although no remarkable difference in prognosis is found between premenopausal and postmenopausal patients in Japan. This suggests that the menopausal status is a critical factor for prognosis among Caucasians, but not among Japanese. As mentioned above, the morbidity and mortality rates of breast cancer among Japanese females are very low, but recently, both morbidity and mortality rates in Japan have been steeply increasing. For example, the mortality rate of breast cancer in Japan almost doubled during the past 20 years. Moreover, biological behavior of breast cancer among Japanese females has been recently changing. And time-trend data clearly indicate that breast cancer in Japan in future will be much more like that in the west, and nowadays it is westernized. PMID- 2195999 TI - [Carcinoembryonic antigen gene family and its clinical application]. AB - Carcinoembryonic antigen (CEA) gene was cloned in 1987. Thereafter, the structures of non-specific cross-reacting antigen (NCA) and biliary glycoprotein I (BGPI) have also been clarified. These three antigens contain immunoglobulin like domains in their basic structures and it could be possible that CEA gene was originated from this basic structure by internal gene multiplication. Each CEA and NCA has hydrophobic domain in the C-terminus consisting of 26 amino acids which is eliminated when it binds with membrane and is reconstituted by combining with phosphatidylinositol glycan, whereas BGPI contains transmembrane and cytoplasmic domains. It is of interest that CEA and NCA have been found to function as adhesion molecules. The structure and possible function of another CEA gene family, PS beta G, were also introduced in this short review. PMID- 2196000 TI - Effect of genetically determined immunodeficiency on epidermal dendritic cell populations in C57BL/6J mice. AB - Mice homozygous for three different recessive mutations known to cause pleiotropic defects in the immune system and in the skin were used to evaluate the relationship between the classical immune system and dendritic epidermal cell populations. Numbers of Langerhans cells (LCs) and Thy-1+ dendritic cells (Thy 1+DEC) were determined using indirect immunofluorescence microscopy of epidermal whole mounts taken from viable motheaten (mev), nude (nu), and rhino (rhhr) mice. All mutants were maintained on the C57BL/6J strain background and were compared with their respective littermate normal controls. Viable motheaten mice had normal numbers of LCs at 1 month of age. However, by 8 weeks of age, LC density had decreased threefold. Nude and rhino mice had normal numbers of LCs at all ages tested. There was no significant effect of the viable motheaten mutation on numbers of Thy-1+DEC. Although nude mice showed normal numbers of Thy-1+ DEC at 1 month of age, these athymic mice had a threefold decrease in numbers of such cells by 6 months. In contrast to the reduced numbers of Thy-1+DEC seen in nude mice, rhino mice showed a four- to fivefold increase in the numbers of these epidermal cells at all ages tested. These findings suggest new mouse models for investigating the development, regulation, and biological properties of epidermal dendritic cell populations. PMID- 2195989 TI - Immunogenicity and immunochemistry of Streptococcus pneumoniae capsular polysaccharides. PMID- 2196001 TI - Actin filament and desmosome formation in cultured human keratinocytes. PMID- 2196002 TI - [Segmental kidney dysplasia]. AB - The frequency of segmental renal dysplasia was studied in 15 patients with complete pyeloureteral duplication whose anatomopathologic diagnosis of the lesions of some of the renal segments of duplication were available (14 partial nephrectomies, one open renal biopsy). Evidence of dysplasia was found in 10 cases (67%), the remaining 5 were diagnosed as having chronic pyelonephritis. All patients had a coexisting ureteric anomaly that drained the dysplastic renal segment: 6 ureteral ectopias, 3 ectopic ureteroceles, 1 vesicoureteral reflux. The clinical and pathogenic importance of the associated anomalies of the excretory tract, the diagnostic difficulties arising from the minimally- or non functioning dysplastic renal segment, and the therapeutic modalities utilized are discussed. PMID- 2196003 TI - [Kidney hydatidosis]. AB - Seven cases of hydatid renal cyst seen at our department over the past 8 years are described. The literature is reviewed and the importance of conservative surgery in the treatment of this disease is highlighted. PMID- 2196004 TI - [Transrectal echography and cancer of the prostate. I. Echographic characteristics]. AB - Our diagnostic criteria in prostatic cancer using transrectal ultrasonography are described herein. A prospective study was undertaken since 1984 in a total of 1,512 patients. 75 of whom had cancer of the prostate. For the present study, we analyzed a series of ultrasonographic parameters that we have termed "intrinsic parameters" (IP) and "morphologic parameters" (MP). IP refer to the echo characteristic of the area within the prostate (intensity of brightness and size of granules) whereas MP refer to the general aspects of the prostate gland (ratio of transverse to anteroposterior diameter, shape deformity and rupture of capsule). The MP have proved to have a more diagnostics capacity; thus, when present, a diagnosis of prostatic cancer is made. IP changes alert us to suspect this condition. A T/AP ratio less than l, a "bell-shaped" prostate, is almost pathognomonic of prostate cancer since the foregoing has not been observed in benign conditions. PMID- 2196005 TI - [Transrectal echography and cancer of the prostate. II. Comparison with digital examination of the rectum]. AB - A comparative study was performed to determine the usefulness and diagnostic capacity in cancer of the prostate afforded by two different techniques: digital examination and transrectal ultrasonography. Our experience in 69 cases of prostate cancer show that more information is provided by transrectal ultrasound. Thus, the diagnostic capacity and usefulness of transrectal ultrasonography in the management of prostate cancer is greater than that of digital examination. However, on the sole basis of the number of cancers diagnosed, both techniques have very similar values for specificity, while transrectal ultrasonography is slightly superior with respect to sensitivity. The foregoing findings simply show that although both techniques have a similar diagnostic capacity, transrectal ultrasonography provides further important information (size, bladder involvement, graphic representation, etc.) that make it overall more useful and superior to the other technique in the management of prostate cancer. PMID- 2196006 TI - [Complete duplication of the urethra]. AB - A case of complete urethral duplication in a child is presented. The malformation consisted of a normal urethra and another epispadial dorsal urethra ending at the dome of the bladder. This is a rare variant of this type of malformation. Incontinence was the surgical indication. The classification, embryology, diagnosis, indications for surgery and treatment of this anomaly are presented. PMID- 2196007 TI - [Halofantrine hydrochloride in the treatment of Plasmodium falciparum malaria in a region of resistance. Analysis of 54 pediatric cases]. AB - 54 children (mean age: 43 months), with initial parasitemia up to 1,000 Plasmodium falciparum isolates per mm3, were treated with halofantrine hydrochloride 8 mg/kg twice daily at 6 hours intervals. 35 of these 54 children had received unsuccessful chloroquine and/or quinine treatment during 15 days before admission to the trial. Fever, which was observed in 52 of the children, and parasitemia disappeared respectively 18 hours and 37 hours after initial administration of the drug (mean values). Clinical and biological tolerance was excellent for all patients. Halofantrine is a new precious alternative for the treatment of malaria in regions with extensive multi-drug resistant strains of Plasmodium. PMID- 2196009 TI - Consequences of rural development on vectors and their control. PMID- 2196008 TI - [The emergence of chloroquine-resistant malaria in Dakar, Senegal]. AB - In October and November 1988 we carried out in vivo Plasmodium falciparum sensitivity tests for chloroquine in the town of Dakar, where malaria is endemic with increased transmission during the rainy season (July to October). 25 mg/kg/p.c of chloroquine has been administered to 35 patients on three consecutive days, according to the WHO protocol. Clinical and parasitological controls were carried out on D1, D2, D3, D4, D7 and D14. We observed two therapeutic failures: one on D7 among the 32 patients examined during that period, and one on D14 among the 24 patients who were present at control. The important drug pressure and population movements in Dakar are sources of chloroquine resistance which should receive special attention in terms of control and surveillance of this emerging problem. PMID- 2196010 TI - Right atrial myxoma originating from the inferior vena cava. AB - A patient undergoing successful excision of a right atrial myxoma arising from the inferior vena cava is reported. The rarity of this case prompted a review of the literature in which only 2 other patients with a right atrial myxoma originating from inferior vena cava tissue were found. PMID- 2196011 TI - Individual ligation technique for lower lobe lobectomy. AB - The classic description of the individual ligation technique for lower lobectomy was published in 1940. Doctor Brian Blades and Dr Edward Kent clearly described the anatomy of the bronchus, pulmonary artery, and vein to both the right and left lower lobes based on their dissection of 83 fresh cadaver lungs. They also provided a detailed description of their recommended technique for dissection, transection, and closure of each major structure. This was an important departure from the previously described mass ligation techniques. This cadaver experience was effectively transferred to the operating room. Kent and Blades reported on 18 patients who underwent lower lobectomy without mortality or the dreaded complication of "putrid empyema." They high-lighted several basic thoracic surgical principles necessary for successful lower lobectomy that are as valid today as they were then. This landmark report provided the impetus for thoracic surgeons to accept lobectomy as a safe and standard anatomical resection. PMID- 2196012 TI - Cardiac function with glucose-insulin-potassium solution. PMID- 2196013 TI - Ventricular septal defect associated with aortic valve incompetence: results of two surgical managements. AB - Aortic valve insufficiency with ventricular septal defect is usually treated by plication of the commissures. However, long-term deterioration is common. We propose a new technique that corrects the aortic annulus dilatation and the leaflet prolapse and reinforces the sinus of Valsalva. Two groups were compared: group I (29 patients) had plication of the prolapsed leaflet(s) and folding of the free edge; group II (26 patients) had triangular resection of the prolapse cusp, annuloplasty, and reinforcement of the aortic wall. The two groups were similar with regarding to preoperative clinical data. There was no perioperative mortality. Primary failure (aortic valve replacement) occurred in 8 patients in group I (28%) and in 2 patients in group II (8%). The rate of secondary failure was 31% in group I and 4% in group II. The actuarial rate of freedom from reoperation at 5 years is 55% in group I and 88% in group II (p less than 0.05). The late mortality was 6.5% in group I and 10.9% in group II (no difference). We conclude that aortic valve insufficiency with ventricular septal defect is a malformation of the aortic leaflets, the annulus, and the sinus of Valsalva, and that the proposed technique offers a better result than the usual methods in terms of residual aortic valve insufficiency. PMID- 2196014 TI - Initial report of the Veterans Administration Preoperative Risk Assessment Study for Cardiac Surgery. AB - This study was authorized by the Department of Veterans Affairs to improve the quality assurance of cardiac surgery by assessing preoperative risk factors and relating them to operative mortality. Data were received on 10,480 patients over a 2-year period. Preoperative risk variables were subjected to univariate and multivariate logistic regression analyses. Significant variables for coronary artery bypass grafting after logistic regression analysis in order of importance are previous cardiac operation, priority of operation, New York Heart Association functional class, peripheral vascular disease, age, pulmonary rales, current diuretic use, and chronic obstructive pulmonary disease. For patients undergoing valve or other cardiac operations with or without coronary artery bypass grafting, those variables found to be significant after multivariate logistic regression analysis are priority of operation; age; peripheral vascular disease; great vessel repair; all other except aortic valve replacement, mitral valve replacement, and great vessel repair; mitral valve replacement; and cardiomegaly. By identifying these current risk factors and the coefficients from the multivariate stepwise logistic regression analysis, expected mortality can be calculated. We propose that the ratio of observed to expected mortality is a better measure of quality of care than unadjusted mortality. PMID- 2196015 TI - Use of glue without graft replacement for type A dissections: a new surgical technique. AB - A new surgical technique for treating type A aortic dissections is described. It consists of the exclusive and extensive use of surgical glue without replacing a segment of the ascending aorta. Since 1984, 21 patients were operated on using this technique. No operative mortality occurred and one reoperation for redissection was required. The technique is simple and safe and yields excellent short-term and long-term results. PMID- 2196016 TI - Development of an artificial heart valve. AB - When I reviewed the 21-year results with the Bjork-Shiley tilting disc valves, I found out that to date, we still have to use these disc valves and all mechanical heart valves with anticoagulation therapy. The highest incidence of valve-related postoperative deaths after aortic valve replacements in Stockholm was anticoagulation-related bleeding, which continued at a rate of about 1% year after year. There is a need to improve the quality of life for heart valve patients, especially for children, for young females who want to have children, for the older generation who are on medical treatment, and for all patients in whom long-term anticoagulation of a perfect quality is impossible to guarantee. A series of tests on goats has been performed, using the Bjork-Shiley Monostrut valve used in 2,024 patients at the Karolinska Hospital in Stockholm and in 75,000 patients worldwide for up to 8 years with a modification of a microporous surface. In the mitral position, this modified partially microporous-surfaced Bjork-Shiley Monostrut valve has permitted goats to live for 5 years with four normal pregnancies without anticoagulation therapy. PMID- 2196018 TI - Cardiac transplantation. PMID- 2196017 TI - Mid-descending aortic traumatic aneurysms. AB - Two patients with traumatic rupture of the mid-descending aorta successfully repaired are presented. Most clinical series of aortic tears do not include this entity. A review of the world literature reveals only 9 previous cases. In 6 of the 11 patients the diagnosis was either missed or delayed. In 4 patients the diagnosis was delayed or missed because of the absence of a superior mediastinal hematoma, and in 2 patients the diagnosis was delayed because of inadequate (single-plane) aortography. Suspicion may be lacking because of absence of the upper mediastinal hematoma considered to be the sine qua non for the diagnosis of aortic rupture. Although deceleration is considered to be the mechanism of injury in tears at the isthmus, severe hyperextension (often associated with fracture dislocation of the underlying thoracic vertebra) is considered to be the causative factor in descending aortic tears. Experience with the 2 patients presented here demonstrates that a high index of suspicion and complete two-plane aortography is required to avoid the potential for catastrophic outcome subsequent to overlooking a tear of the mid-descending aorta. PMID- 2196019 TI - Carcinoid tumors of the thymus. AB - Carcinoid tumors arising in the thymus are rare. Since Rosai and Higa in 1972 distinguished these neoplasms from thymomas, fewer than 100 cases have been reported in the world literature. In a 38-year review (1950 to 1988) of surgically treated thymic tumors at Henry Ford Hospital, only 7 cases of thymic carcinoids were identified. These 6 men and 1 woman ranged in age from 27 to 70 years (mean, 48 years) at diagnosis. Follow-up was available in all patients with the longest survival being 12 years in 2 patients, and the shortest, 1 year, in 1. Recurrences and/or metastases developed in 4 of 7 patients between 1 and 9 years after initial resection. Recurrences were treated by reexcision in addition to radiation treatment and chemotherapy in 3 patients and reexcision with radiation treatment alone in 1 patient. A review of the literature along with our experience suggests that thymic carcinoids have a biological behavior distinct from thymoma in terms of cell origin, associated syndromes, neoplastic behavior, and prognosis. An aggressive surgical approach with complete initial excision of the tumor and of subsequent recurrences, along with radiation and probably chemotherapy, is the best available treatment today. PMID- 2196020 TI - Sutureless ring graft replacement of ascending aorta and aortic arch. AB - Complications after aortic replacement that result from prolonged graft insertion time and technical difficulties with suturing through friable, diseased aortic tissue can be addressed with use of the sutureless intraluminal ring graft. Between 1978 and 1989, we replaced the ascending aorta or aortic arch with this device in 49 patients. At no time were we unable to use a sutureless graft during a procedure. Twenty-eight cases of aneurysmal disease and 21 cases of acute or chronic dissection were treated. Twenty-six patients required replacement of the aortic valve, with annuloartic ectasia being the most common indication (71%). Ten patients underwent concomitant coronary artery bypass grafting. The operative mortality rate for ascending aortic aneurysm repairs was 4%, and that for dissections was 18%. Five of 8 patients requiring aortic arch replacement survived. Most patients were studied angiographically before discharge. No complications were related to anastomotic hemorrhage, pseudoaneurysm formation, graft migration, or thromboemboli. Individual cases of phrenic nerve palsy, acute tubular necrosis, and transient ischemic attack, all of which resolved completely, were identified. The actuarial 5-year survival rate is 64%. We conclude that modification of the sutureless intraluminal ring graft to suit the pathology encountered at operation allows the quickest repair with the least chance of anastomotic complication. PMID- 2196021 TI - Prophylactic digitalization for thoracotomy: a reassessment. AB - A prospective, controlled, randomized clinical study of 140 patients undergoing elective thoracic operations over a period of 1 year in a regional referral unit was performed in which one group received digoxin and the other did not. The incidence of cardiac arrhythmia was compared in each group. Overall mortality was 5.7%. There was no significant difference in incidence of cardiac arrhythmia in each group, and we conclude that the prophylactic use of digoxin in elective thoracic operations should be revised. PMID- 2196022 TI - Gastrointestinal tract hemorrhage. The value of a nasogastric aspirate. AB - A bloody nasogastric aspirate is believed to imply active upper gastrointestinal tract bleeding, while a nonbloody yellow-green nasogastric aspirate that contains duodenal secretions suggests the absence of bleeding proximal to the ligament of Treitz. To validate these beliefs, physicians were asked to predict the presence of active gastrointestinal tract bleeding and whether bile was present in a nasogastric aspirate obtained immediately before endoscopy in 73 episodes of bleeding in 62 patients. A relationship was found between the physician's assessment of the presence of active bleeding demonstrated endoscopically and the appearance of the nasogastric aspirate. However, the sensitivity and specificity were low (79% and 55%, respectively). No association between the assessment of bile in the nasogastric aspirate and the presence of bile acids was demonstrated. These data do not support the placement of a nasogastric tube to determine whether or not a patient is bleeding, the location of the bleeding, and whether endoscopy should be performed. PMID- 2196023 TI - Is the lung a 'target organ' in diabetes mellitus? AB - Histopathologic evidence of lung involvement in subjects with diabetes mellitus has included thickened alveolar epithelial and pulmonary capillary basal laminae, the latter being suggestive of existing pulmonary microangiopathy. Abnormal pulmonary function has been detected in some diabetic patients; the most consistent abnormalities are reduced lung volumes in young (aged less than 25 years) insulin-dependent diabetic subjects, reduced pulmonary elastic recoil in both young and adult (aged greater than 25 years) diabetic subjects, and impaired diffusion due to a reduced pulmonary capillary blood volume in the adult group. Nonenzymatic glycosylation-induced alteration of lung connective tissue is the most likely pathogenetic mechanism underlying mechanical pulmonary dysfunction in diabetic subjects, while the most tenable explanation for impaired pulmonary microangiopathy. these patients is the presence of underlying pulmonary microangiopathy. The finding of abnormal lung function in some diabetic subjects suggests that the lung should be considered a "target organ" in diabetes mellitus; however, the clinical implications of these findings in terms of respiratory disease are at present unknown. PMID- 2196024 TI - Asymptomatic bacteriuria. Which patients should be treated? AB - Asymptomatic bacteriuria is common in both the community nursing home and hospital settings. Few data, however, are available about the potential complications arising from asymptomatic bacteriuria (eg, the development of symptomatic infection and renal damage) for various patient populations and for various medical conditions. On the basis of data in the literature, we believe that neonates and preschool children with asymptomatic bacteriuria should be treated. Pregnant women and "nonelderly" (less than 60 years old) men should be treated. We do not think that school-age children, nonpregnant, nonelderly women, or elderly men and women need antimicrobial treatment if their urinary tracks are normal. In addition, antimicrobial treatment is recommended for patients with asymptomatic bacteriuria and abnormal urinary tracts and those undergoing clean intermittent catheterization, genitourinary manipulation, or instrumentation. Patients with long-term indwelling catheters should not be treated. The treatment of asymptomatic bacteriuria in patients with short-term indwelling catheters and those with ileal conduits is controversial. These treatment recommendations should not necessarily be accepted as the standards of practice, since treatment is often controversial due to the lack of published data describing the natural course of asymptomatic bacteriuria in various patient populations. PMID- 2196025 TI - How common is postpartum thyroiditis? A methodologic overview of the literature. AB - The incidence of postpartum thyroiditis (PPT) in the general population has been reported to range from 1.9% to 16.7%, depending on the study. To determine whether bias may have played a role in the generation of these widely varying estimates, a set of methodologic criteria were applied to the published original research dealing with the epidemiology of PPT. The articles that passed these methodologic filters reported a narrow range of incidences of PPT, varying between 3.7% and 5.9%. Reanalysis of these articles confirmed that thyrotoxicosis occurred more frequently in the first 3 months post partum than did hypothyroidism, and that a positive antimicrosomal antibody titer was strongly associated with postpartum thyroid dysfunction (odds ratio, 86.6; 95% confidence interval, 45.9 to 163.2). This article suggests that PPT is a common condition that occurs in the postpartum period. The best estimate of the incidence of PPT in an unselected cohort of postpartum women is 4.9%. PMID- 2196026 TI - A conservative procedure for the diagnosis of catheter-related infections. AB - A prospective study was done in 139 intravascular catheters (IVCs) that had been removed for different reasons. The purpose of the study was to compare laboratory procedures for the diagnosis of catheter-related infections and also to attempt to clarify the present controversy regarding the portal of entry of such infections. The IVCs were removed by one of us and multiple samples were studied according to a standard procedure. Semi-quantitative cultures were performed of the tips, the interior of the hub, and the skin around the insertion point. Quantitative cultures were performed of the infusion fluid and of the IVC tips. Of the 139 IVCs studied, 53 (38.1%) were infected (greater than or equal to 15 colony-forming units per plate in the semiquantitative culture). Semi quantitative and quantitative cultures gave comparable results, but the semiquantitative procedure proved to be easier and faster. All but three infected catheters had a positive (greater than or equal to 15 colony-forming units per plate) skin and/or hub culture (superficial cultures), with microorganisms identical to those isolated in the IVC tip. Our results showed two possible and differentiable portals of entry. Thirty (56.6%) had external origin (semiquantitative skin culture positive), 12 (22.6%) had an internal origin (semiquantitative hub culture positive), and 8 (15.1%) had both origins. All catheters with negative superficial cultures had a negative tip. The predictive value of positive superficial cultures in the diagnosis of catheter-related infection was 66.2% and that of negative cultures was 96.7%. In patients with suspected catheter-related infections but negative superficial cultures, the possibility of infection may reasonably be ruled out, thereby avoiding many unnecessary catheter withdrawals. PMID- 2196027 TI - Cystic thyroid nodules. The dilemma of malignant lesions. AB - A retrospective study of 221 surgically resected thyroid nodules disclosed that 71 (32%) were cystic and 150 (68%) were solid lesions. Ultrasonography correctly characterized cystic nodules in all but one case. Comparing cystic and solid nodules, there were no differences in patient demographics (mean ages, 47.7 +/- 1.8 SEM vs 45.9 +/- 1.2 years; sex, 78% females both groups), the proportion that were solitary (39% vs 40%), or the nodule size (49% vs 47% greater than or equal to 2 cm in diameter). Of cystic thyroid lesions, 4% were simple cysts, 82% were degenerating benign adenomas or colloid nodules, and 14% were malignant compared with 23% of solid lesions that were malignant. Most cystic lesions (81%) contained bloody fluid. One benign true cyst was filled with thick brown fluid, while clear yellow fluid was repeatedly aspirated from one malignant cystic nodule. Malignant fine-needle aspiration cytology was the best predictor of cancer (100%). Much less predictable were signs of local compression or invasion (43%), a history of head or neck irradiation (33%), cyst recurrence after aspiration (29%), or an increase in the cystic nodule's size (7%). Indeterminate cytology identified malignancy with about half the frequency in cystic lesions as compared with solid nodules (13% vs 27%). The only false-negative fine-needle aspiration cytology occurred in a cystic lesion. In patients with cystic papillary cancers, needle aspirates contained insufficient material for diagnosis in 20% that occurred in no patient with solid papillary carcinoma. The sensitivities and specificities of fine-needle aspiration cytology for solid nodules were 100% and 55%, and for cystic nodules were 88% and 52%. Thus, cystic lesions are as likely as solid thyroid lesions to harbor a malignancy that cannot be predicted from the cyst's clinical characteristics or the patient's demographic data. Although fine-needle biopsy is the best predictor of malignancy in either cystic or solid thyroid lesions, it is slightly less reliable when a thyroid lesion is fluid filled rather than solid. We believe that most cysts not abolished by aspiration should be surgically excised. PMID- 2196028 TI - A gonadotropin releasing hormone analogue prevents cyclical attacks of porphyria. AB - Acute intermittent porphyria is a genetic disease in which endogenous hormones affect clinical expression. Premenstrual exacerbations can occur, sometimes often, in women with this disease. Gonadotropin releasing hormone analogues can prevent ovulation by reducing secretion of luteinizing hormone and follicle stimulating hormone. In six patients with well-documented acute intermittent porphyria and frequent cyclical exacerbations, daily administration of an agonistic gonadotropin releasing hormone analogue, ([ImBzl]-D-His6,Pro9 NET)gonadotropin releasing hormone, intranasally or subcutaneously for as long as 26 months reduced or eliminated premenstrual attacks and caused only minor side effects. Adjustments in dosage or route of administration were sometimes needed. We conclude that endocrine manipulation by treatment with a gonadotropin releasing hormone agonist will prevent neurovisceral attacks of acute intermittent porphyria due to cyclical changes in endogenous hormones and is a safe alternative to exogenous steroids, which may induce attacks of this disease. PMID- 2196029 TI - Aerobic nitrate and nitrite reduction in continuous cultures of Escherichia coli E4. AB - Nitrate and nitrite was reduced by Escherichia coli E4 in a L-lactate (5 mM) limited culture in a chemostat operated at dissolved oxygen concentrations corresponding to 90-100% air saturation. Nitrate reductase and nitrite reductase activity was regulated by the growth rate, and oxygen and nitrate concentrations. At a low growth rate (0.11 h-1) nitrate and nitrite reductase activities of 200 nmol.mg-1 protein.min-1 and 250 nmol.mg-1 protein.min-1 were measured, respectively. At a high growth rate (0.55 h-1) both enzyme activities were considerably lower (25 and 12 nmol mg-1.protein.min-1). The steady state nitrite concentration in the chemostat was controlled by the combined action of the nitrate and nitrite reductase. Both nitrate and nitrite reductase activity were inversely proportional to the growth rate. The nitrite reductase activity decreased faster with growth rate than the nitrate reductase. The chemostat biomass concentration of E. coli E4, with ammonium either solely or combined with nitrate as a source of nitrogen, remained constant throughout all growth rates and was not affected by nitrite concentrations. Contrary to batch, E. coli E4 was able to grow in continuous cultures on nitrate as the sole source of nitrogen. When cultivated with nitrate as the sole source of nitrogen the chemostat biomass concentration is related to the activity of nitrate and nitrite reductase and hence, inversely proportional to growth rate. PMID- 2196031 TI - [Apropos of prenatal screening of tracheal and laryngeal atresia]. PMID- 2196030 TI - [Treatment of severe hyaline membrane disease with a single-dose of natural exogenous surfactant of porcine origin. A randomized trial: immediate effects and outcome at 28 days of life]. AB - The results obtained with porcine surfactant (Curosurf) administration for the treatment of hyaline membrane disease (HMD) are reported. Thirty premature infants weighing 700 to 2,000 g with severe HMD (mechanical ventilation and oxygen requirement (FiO2) greater than 60% were randomly allocated at 2 to 15 hours postnatal age. Eight of the 30 patients included in this group participated in a multicenter european trial. The fifteen infants with mean gestational age (GA) of 29.5 weeks included in the treatment group (T), were treated at 8.6 hours of life with a single dose of 200 mg/kg Curosurf given intratracheally while 15 infants of mean GA 30 weeks formed the control group (C). Infants in the T group showed an immediate, dramatic and sustained improvement of oxygenation as reflected by increased PaO2/FiO2 and arterial to alveolar PO2 ratios within 1 hour. This significant improvement in favor of T group (p less than 0.005) persisted for 2 days when control infants began to recover. This improvement in oxygenation allowed a significant decrease of FiO2 (p less than 0.005) and mean airway pressure (p less than 0.01) in the T group within 1 hour and up till the second day. Despite this early improvement obtained with Curosurf the survival rate at 28 days of life and the incidence of associated HMD complications were not significantly modified. However the tendency was towards decreased respiratory morbidity. The discussion will consider the value of multiple doses. PMID- 2196032 TI - The management of splenic trauma in a trauma system. AB - Large teaching centers have reported splenic salvage rates of 40% to 50% in adults after splenic trauma. It is unknown whether similar salvage rates can be achieved safely in community trauma centers with a lower volume of patients and less experience. Between August 1984 and August 1988, 117 patients with splenic injury were treated at a level I center and 311 were treated at four level II centers. Splenectomy was performed in 252 patients (59%), splenorrhaphy was performed in 160 patients (37%), and 16 patients (4%) were observed. While the splenic salvage rate was higher at the level I center (50% vs 38%), selective splenorrhaphy was successful in the level II centers where the volume of splenic injury was lower (15 to 25 cases per year). PMID- 2196034 TI - [An insufficiency of essential trace elements and its manifestations in pathology]. AB - There exist 11 essential elements (iron, copper, iodine, zinc, chromium, cobalt, molybdenum, manganese, nickel, selenium and fluorine) vitally important for human health. The deficiency of these trace elements results in many pathological processes, including such world-wide human diseases, as iron-deficient anemias and other forms of hyposiderosis, endemic hypothyroid goiter, endemic fluorine deficiency states, particularly manifested by dental caries in children and osteoporosis of the advanced age. Selenium deficiency causes endemic cardiopathy in China, is a risk factor for the development and severe course of congestive cardiopathies, as well as myocardial infarction in a number of European countries. Correction of selenium deficiency with sodium selenite reduced to the minimum the mortality rate from endemic cardiopathy in China (Keshan disease) and had a favourable effect on other forms of cardiovascular pathology. Essential trace element deficiency results in many forms of embryonal and fetal pathology and decreases the antitumour resistance in man. New essential trace elements are still being identified and their number reached 19 at present. Development of pathological anatomy of essential trace element deficiency is an important task of modern medicine. PMID- 2196033 TI - Immunity to human and bovine respiratory syncytial virus. AB - Human and bovine respiratory syncytial viruses resemble each other closely. During annual winter outbreaks, they cause similar respiratory tract disease in infants and calves. The disease is most severe in children and calves between 1 and 3 months old, when maternal antibodies against the virus are usually present. Reinfections, which are common, are accompanied by progressively milder illnesses in children, but are symptomless in calves. Because maternal antibodies suppress serum and mucosal antibody responses of all isotypes, the development of a vaccine that is effective in young children and calves with high levels of maternal antibodies has been severely hampered. Although virus administered intranasally to young calves with maternal antibodies does not evoke antibody responses, it can prime these calves for a protective memory response upon reinfection. Protection appears to be associated with the capacity to mount a mucosal memory IgA response. There are several indications that one or more immunopathologic mechanisms contribute to the disease. An Arthus reaction (type III) may have a role in the pathogenesis, because activated complement may cause most of the pathologic lesions, including edema and emphysema in uninfected parts of the lung. Lungs from calves with severe or fatal disease have depositions of complement component C3 and a low histamine content. The most immunogenic and protective antigen of the virus is the fusion (F) glycoprotein, which evokes a strong antibody response and is a target for cytotoxic T cells. On the F protein, epitopes that induce neutralizing and non-neutralizing antibodies, both of which may enhance complement activation, were identified. Immunity to the F protein may have beneficial and harmful effects. PMID- 2196036 TI - Early vitrectomy for severe vitreous hemorrhage in diabetic retinopathy. Four year results of a randomized trial: Diabetic Retinopathy Vitrectomy Study Report 5. AB - Six hundred sixteen eyes with recent severe diabetic vitreous hemorrhage reducing visual acuity to 5/200 or less for at least 1 month were randomly assigned to either early vitrectomy or deferral of vitrectomy for 1 year. The proportion of eyes with visual acuity of 10/20 or better was higher in the early vitrectomy group than in the deferral group throughout the 4-year follow-up period. Up to the 18-month visit, the early group had a higher proportion of eyes with visual acuity of no light perception. An increased chance of obtaining good vision with early vitrectomy was clearly present in the type I diabetes group, particularly in patients who developed severe vitreous hemorrhage after less than 20 years of diabetes, a patient group tending to have more severe proliferative retinopathy. This advantage was not found in the type II diabetes group, in which patients were older and tended to have less severe retinopathy. The findings of this and previous Diabetic Retinopathy Vitrectomy Study reports support early vitrectomy in eyes known or suspected to have very severe proliferative diabetic retinopathy as a means of increasing the chance of restoring or maintaining good vision. PMID- 2196038 TI - Ganzfeld blankout occurs in bowl perimetry and is eliminated by translucent occlusion. AB - An intermittent darkening of the visual field (ganzfeld "blankout") is perceived during bowl perimetry. Since this may be a form of rivalry, we hypothesized that occluding the nontested eye with a translucent occluder may eliminate the phenomenon. Ten normal subjects underwent visual field testing with both a translucent and an opaque occluder. Eight of the 10 reported darkening to occur with the opaque patch, while none reported it with the translucent occluder. The darkening occurred with a mean latency of 10.9 seconds, occupied 34.4% of the time, and on average occurred 3.25 times per minute. With the translucent occluder, retest threshold variability was 18.8% less and sensitivity was increased by 0.7 dB. The elimination of this darkening using translucent occluders in bowl perimetry will allow reduced variability and increased sensitivity and comfort. PMID- 2196035 TI - [Antigenic markers of precancer and cancer of the stomach]. AB - Three groups of antigens are distinguished: 1) those of normal stomach mucous membrane, 2) antigens characteristic of metaplastic epithelium in the enterolized mucous membrane; 3) other antigens. Each of these antigens is considered separately. Stomach, intestinal, oncofetal ectopic and other antigens expression allows to distinguish varieties of the stomach tissue differentiation and the features of the morphofunctional modification of the precancerous mucous membrane. PMID- 2196037 TI - Localized suprachoroidal hematomas. Ophthalmoscopic features, fluorescein angiography, and clinical course. AB - We describe the ophthalmoscopic characteristics, fluorescein angiographic features, and clinical course of four patients with a localized suprachoroidal hematoma. Each of the four patients developed a darkly pigmented fundus lesion a short time following uncomplicated intraocular surgery. In every case, the lesion appeared ophthalmoscopically similar to a choroidal malignant melanoma. However, fluorescein angiography showed neither choroidal fluorescence blockage nor the double-circulation pattern characteristic of choroidal melanomas. Instead, each lesion exhibited a central fluorescein pattern similar to that of the surrounding uninvolved choroid, relative marginal hypofluorescence, and overlying choroidal folds. Ultrasonography revealed acoustic hollowness of each lesion without choroidal excavation. The lesions disappeared completely within 1 to 2 months, leaving no visible trace. We discuss the differential diagnosis of these lesions and stress the diagnostic value of fluorescein angiography. PMID- 2196039 TI - "Portal" adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. PMID- 2196040 TI - Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease. AB - Several epidemiological studies have reported that the regional distribution of body fat is a significant and independent risk factor for cardiovascular disease (CVD) and related mortality. Although these associations are well established, the causal mechanisms are not fully understood. Numerous studies have, however, shown that specific topographic features of adipose tissue are associated with metabolic complications that are considered as risk factors for CVD such as insulin resistance, hyperinsulinemia, glucose intolerance and type II diabetes mellitus, hypertension, and changes in the concentration of plasma lipids and lipoproteins. The present article summarizes the evidence on the metabolic correlates of body fat distribution. Potential mechanisms for the association between body fat distribution, metabolic complications, and CVD are reviewed, with an emphasis on plasma lipoprotein levels and plasma lipid transport. From the evidence available, it seems likely that subjects with visceral obesity represent the subgroup of obese individuals with the highest risk for CVD. Although body fat distribution is now considered as a more significant risk factor for CVD and related death rate than obesity per se, further research is clearly needed to identify the determinants of body fat distribution and the causal mechanisms involved in the metabolic alterations. It appears certain, however, that an altered plasma lipid transport is a significant component of the relation between body fat distribution and CVD. PMID- 2196041 TI - Prevention of myocardial lesions in JCR:LA-corpulent rats by nifedipine. AB - Male rats of the JCR:LA-corpulent strain spontaneously develop atherosclerosis and myocardial lesions if corpulent. The corpulent rats exhibit a marked very low density hyperlipidemia and insulin resistance. The incidence of both vascular and myocardial lesions correlates strongly with the hyperinsulinemia, but not with the hyperlipidemia. Corpulent male rats were chronically treated with nifedipine or acetylsalicylic acid to explore the roles of smooth muscle spasm and platelet activity in induction of the myocardial lesions. Acetylsalicylic acid treatment was associated with no significant changes in fasting glucose, insulin, or lipid concentrations. Nifedipine caused no significant changes in glucose concentration but was associated with mildly increased insulin levels. Treatment with nifedipine resulted in significant decreases in serum triglyceride concentrations. The decreases were confined to longer-chain triacylglycerol molecular species with no change in the concentration of molecular species with 48 or 50 acyl carbon atoms. There was no effect on myocardial lesion frequency with acetylsalicylic acid treatment. In contrast, nifedipine prevented the development of old organized scarred lesions. This effect is similar to that seen with treatments that markedly reduce the insulin resistance. These findings suggest that platelet-initiated thrombus formation is not an important factor in lesion formation in the JCR:LA-cp rat, but that smooth muscle spasm is probably important. PMID- 2196042 TI - Epidemiologic studies on infectious coryza outbreaks in northern New South Wales, Australia, using serotyping, biotyping, and chromosomal DNA restriction endonuclease analysis. AB - The epidemiology of 16 cases of infectious coryza, an upper respiratory tract disease of chickens caused by Haemophilus paragallinarum, was investigated in a retrospective study. The cases occurred over a 14-month period on 10 farms in northern New South Wales. The available field data indicated that the cases formed six unrelated outbreaks. The 16 isolates of H. paragallinarum were subjected to serotyping by the Page and Kume schemes and biotyping based on carbohydrate fermentation and antimicrobial drug-resistance patterns. As well, newer fingerprinting techniques--plasmid profiles, whole-cell protein profiles, immunoblots of whole-cell protein profiles and total DNA restriction endonuclease analysis (REA)--were evaluated. Antimicrobial biotyping and REA profile typing proved most useful, allowing the recognition of three groups among the isolates. The other techniques gave either limited or no subdivision among the isolates. The combined results of the laboratory study indicated that, rather than six unrelated outbreaks, the 16 isolates represented three pairs of related outbreaks. This study represents the first application of sensitive biotyping and fingerprinting techniques to outbreaks of infectious coryza. The results have established that farms can be repeatedly infected with a single strain of H. paragallinarum that re-emerges at intervals. This study also obtained the first detailed evidence that replacement stock are a major source of infectious coryza. PMID- 2196043 TI - Replication of a waterfowl-origin influenza virus in the kidney and intestine of chickens. AB - Intravenous inoculation of chickens with a waterfowl-origin type A influenza virus resulted in high titers of virus in kidney tissues and viral nucleoprotein in renal tubular epithelial cells and in intestinal mucosal epithelial cells. Virus titers in kidneys of four of eight clinically normal chickens sampled on days 3 and 5 postinoculation (PI), one dead chicken on day 3 PI, and one dead chicken on day 7 PI exceeded 10(6) mean embryo infectious dose per gram of tissue. Using immunofluorescent and immunoperoxidase staining, viral nucleoprotein was identified in the cytoplasm and nucleus of tubular epithelial cells in kidneys and in nucleus of mucosal epithelial cells lining villi in the lower small intestine. Based on the low intravenous pathogenicity index for this virus (0.3) along with the high virus titers in kidney tissues and localization of viral antigen in kidney important site for replication of avian influenza (AI) virus of low pathogenicity. Recovery of type A influenza viruses from cloacal swabs could result from viral replication in kidneys as well as in the lower intestine and/or the bursa of Fabricius. PMID- 2196044 TI - Homogeneity of characteristics of Pasteurella multocida isolated from turkeys and wildlife in California, 1985-88. AB - Five hundred twenty isolates of Pasteurella multocida, collected in California from September 1985 to November 1988, were characterized in the laboratory. Characteristics examined included serotype, capsular type, biotype (subspecies), and possession of plasmid DNA. Three hundred thirty-three isolates recovered from turkeys dying from fowl cholera, 88 isolates from liver turkeys in flocks with fowl cholera outbreaks in the recent past, and 99 isolates from wildlife captured on fowl cholera-outbreak and non-outbreak turkey premises were studied in this manner. Characteristics were fairly homogeneous among isolates, especially those obtained from turkeys. The majority of isolates were serotype 3,4, capsular type A, subspecies multocida, and lacked plasmid DNA. Common serotypes of isolates from turkeys and wildlife sampled on the same premises were noted in eight of 13 cases examined. PMID- 2196045 TI - Reduction of Salmonella typhimurium concentration in broiler chickens by milk or whey. AB - Whey (5%) in the feed of chicks for the first 10 days of life reduced the mean log10 number of viable S. typhimurium from 5.68 in control chickens to 3.38 in whey-fed chickens. Lactose in drinking water or reconstituted dry milk (5% wt: vol) in drinking water reduced the mean log10 number of S. typhimurium to 2.60 and 2.11, respectively. Milk (5% wt: wt) in feed was not effective in reducing S. typhimurium colonization. The lack of effect of milk in the feed is believed to be because not enough lactose was provided at the 5% (wt: wt) concentration. Lactose in whey or nonfat dried milk offers alternatives to the use of pure lactose in preventing or lowering S. typhimurium numbers in young broiler chickens. PMID- 2196046 TI - Production of Salmonella enteritidis-contaminated eggs by experimentally infected hens. AB - Laying hens of three different ages were experimentally infected with a strain of Salmonella enteritidis by either oral inoculation or contact transmission. Total egg production was depressed in exposed hens of all three age groups. Persistent intestinal shedding was observed in a small number of hens. Eggs with contents contaminated by S. enteritidis were produced by exposed hens at a high frequency, but only during a fairly short period of time that extended through approximately 1 week postinoculation for older hens and through 2 weeks for younger hens. S. enteritidis was recovered from whole yolks and albumen of these eggs at similar frequencies, but not from the content of yolks. Eggs with contaminated shells were also produced, but at a lower frequency. Contaminated eggs were produced by orally inoculated and contact-exposed hens at similar frequencies. S. enteritidis was not isolated from the contents of eggs laid by hens infected with other S. enteritidis strains. PMID- 2196047 TI - Stunting syndrome in turkeys. Development of an experimental model. AB - Experiments were conducted to establish a stunting syndrome (SS) model to facilitate research on nutritional aspects of enteric disorders of poults. One day-old turkeys were dosed per os with tryptose phosphate broth (TPB) (controls) or inoculum (inoculated). The inoculum was prepared by homogenizing intestines from 11-day-old commercial poults diagnosed to have SS in TPB (1:0.5 [wt:wt]). Subsequently, intestines from 8-day-old inoculated poults from the previous experiment were used. Inoculation reduced growth (P less than 0.001) and feed consumption (P less than 0.001) at 8 and 14 days of age. In Expts. 1, 2, and 3, gain of inoculated poults was 60.9%, 58.8%, and 52.6% that of controls up to 8 days of age and 77.9%, 76.6%, and 80.9% that of controls from 8 to 15 days of age, respectively. Feed conversion was impaired (P less than 0.001) up to 8 days of age. The activity of maltase and sucrase in the jejunum and of pancreatic enzymes was determined every 2 days up to 13 days of age. Inoculation decreased (P less than 0.001) maltase and sucrase starting at 3 days of age (i.e., maltase activity was 17.45 and 1.70 mumols maltose hydrolyzed/hr.mg protein in control and inoculated poults, respectively). Inoculation had no effect on pancreatic lipase, amylase, or trypsin. PMID- 2196048 TI - Salmonella typhimurium penetration through the eggshell of hatching eggs. AB - This study was undertaken to demonstrate penetration of Salmonella typhimurium through the eggshell of newly laid broiler hatching eggs. Eggs were challenged either by lightly spraying the bacteria over the blunt end of the egg or by contact with contaminated dry nest litter. Exposure time for both groups was 10 minutes; afterward, all eggs were disinfected and incubated 19 days under normal conditions. Chorioallantoic membranes and yolk sacs were cultured in brain-heart infusion broth on day 19 to demonstrate penetration. Isolation of the bacteria from chorioallantoic membranes and yolk sacs, respectively, were as follows: sprayed group: 100% and 83%; contact group: 59% and 29%. These results showed that although water enhanced S. typhimurium penetration, its presence on the eggshell is not essential for penetration to occur. PMID- 2196049 TI - The thin ideal, depression and eating disorders in women. AB - It is proposed that a cultural ideal of thinness for women causes depression at a higher rate among women than among men. This model accounts for five currently unintegrated trends in the epidemiology of depression. It explains why: (1) twice as many women as men are likely to be depressed; (2) this sex difference emerges at puberty; (3) this sex difference is only found in western countries; (4) there is more depression today; (5) the average age of onset for depression is younger now than in the past. Four parallel trends in eating disorders can also be accounted for by the same factor. PMID- 2196050 TI - Eukaryotic transcription factors. AB - Many nuclear proteins have been found recently to interact with short conserved sequences which are involved in regulating the transcription of various genes. Nuclear transcription factors may be arbitrarily subdivided into two groups, ubiquitous and tissue-specific. The transcription of one gene is usually regulated by several factors which interact with different sequences located either in the promoter region of the gene or outside it. The appearance or disappearance of transcription factors for some genes corresponds to certain phases of cell differentiation or dedifferentiation and even to individual stages of the cell cycle. PMID- 2196051 TI - Induction of a phosphomannosyl binding lectin activity in Giardia. AB - Giardia lamblia, a protozoan parasite that causes widespread diarrheal disease, expresses a surface membrane associated lectin, taglin, which is specifically activated by limited proteolysis with trypsin, a protease that is present in abundance at the site of infection. When activated, taglin agglutinates enterocytes which are the cells to which the parasite adheres in vivo, and in addition, binds to isolated brush border membranes of these cells. These findings suggest that this lectin may be involved in the host-parasite interaction. Taglin is most specific for terminal phosphomannosyl residues and its binding to red cells is mediated by cell surface phosphate residues. Hemagglutinating activity induced by taglin is most active at pH 6.5 and is dependent on divalent cations. A monoclonal antibody to taglin reacts with the surface membrane of live trophozoites and recognizes a protein of 28/30 kDa in lysates of Giardia trophozoites, by immunoblotting. This finding is confirmed by direct demonstration of lectin activity by erythrocyte binding to proteins electroblotted to nitrocellulose, which revealed specific red cell binding to giardial protein bands in the same molecular weight range as those recognized by the monoclonal antibody. PMID- 2196052 TI - Topogenesis of peroxisomal proteins. AB - Molecular and biochemical analysis of the biogenesis of peroxisomes has made rapid progress in recent years. Research on the mechanism of targeting of peroxisomal proteins has revealed that many, but not all, peroxisomal proteins have a conserved tripeptide motif in their carboxy-terminal portions which is required for entry into peroxisomes; the topogenic signal mechanism thus differs in these instances from those employed in mitochondria and endoplasmic reticulum. Other factors involved in peroxisome biogenesis are also coming to light. PMID- 2196053 TI - DNA polymerase delta: a second eukaryotic DNA replicase. AB - During the past few years significant progress has been made in our understanding of the structure and function of the proteins involved in eukaryotic DNA replication. Data from several laboratories suggest that, in contrast to prokaryotic DNA replication, two distinct DNA polymerases are required for eukaryotic DNA replication, i.e. DNA polymerase delta for the synthesis of the leading strand and DNA polymerase alpha for the lagging strand. Several accessory proteins analogous to prokaryotic replication factors have been identified and some of these are specific for pol delta whereas others affect both DNA replicases. The replicases and their accessory proteins appear to be highly conserved in eukaryotes, as homologous proteins have been found in species ranging from humans to yeast. PMID- 2196054 TI - Nucleosome segregation--divided opinions? PMID- 2196055 TI - Short cuts for genomic walking: chromosome microdissection and the polymerase chain reaction. PMID- 2196056 TI - Magnesium induced activation of endogenous nucleases from isolated yeast nuclei: liberation of chromatin fragments of mono- and oligo- nucleosome size. AB - Isolated yeast nuclei were subjected to autodigestion by Mg2(+)-activated endogenous nucleases. The nuclear digests were analysed for their chromatin components. Gel electrophoresis and melting temperature analyses revealed the presence of DNA organized into nucleosomes. Our results demonstrate that magnesium activated endogenous endonucleases of yeast digest the chromatin into mono- and oligo- nucleosomal size fragments. PMID- 2196057 TI - Rapid increase of cellular UDP-glucuronide after mitogen stimulation of quiescent 3T3 mouse fibroblasts. AB - Chromatographic analysis of the acid soluble nucleotide pool in 3T3 fibroblasts 30 minutes after serum stimulation revealed one component that was increased compared to quiescent controls. This component was identified as UDP-glucuronide by chromatographic and chemical means. The time course and magnitude of the serum stimulated increase in UDP-glucuronide is similar to the time course and magnitude of the increase in [14C]uridine uptake. Other factors capable of stimulating [14C]uridine uptake, including epidermal growth factor, platelet derived growth factor, interleukin-1, and a phorbol ester also caused an increase in UDP-glucuronide. The results show that one of the earliest changes in pyrimidine nucleotide metabolism after mitogen stimulation is an increase in UDP glucuronide synthesis, which may be related to increased uridine uptake. PMID- 2196058 TI - Modulation of insulin receptors and catecholamines in rat brain in hyperthyroidism and hypothyroidism. AB - Insulin receptor activity and its relationship with catecholamines and serotonin were investigated in rat brain using Triton X-100 extracts from total membranes, synaptosomes and choroid plexus in experimental hypothyroidism and hyperthyroidism. Insulin receptor activity was assessed by binding to [125I]insulin and catecholamines by high performance liquid chromatography. In choroid plexus thyronines effects are well pronounced and there is modulation vis a vis plasma hormone concentrations. Triiodothyronine levels increase in brain in all experimental groups. This suggests that rat may serve as a useful model for thyronine homeostasis in brain and there may be involvement of very complex regulatory mechanisms in glucose tolerance. PMID- 2196059 TI - Histologic and electron microscopic characterization of the antiperinuclear factor antigen. AB - The presence of the antiperinuclear factor, an autoantibody that recognizes cytoplasmic antigens, was detected in sera from patients with rheumatoid arthritis (59%), seronegative rheumatoid arthritis (36%), systemic lupus erythematosus (46%), systemic sclerosis (26%), and in nonautoimmune controls (10%). The antigenic perinuclear granules were found in the stratum intermedium layer of the buccal mucosa. Granules exhibited histologic features of nucleoproteins, stained for ribonucleoprotein, and showed the ultrastructural characteristics of aggregated rough endoplasmic reticulum. The antiperinuclear factor may recognize a common autoantigen in connective tissue disease. PMID- 2196060 TI - Conversion of stable renal allografts at one year from cyclosporin A to azathioprine: a randomized controlled study. AB - Seventy-seven stable, nondiabetic, cadaveric renal transplants were randomized at 1 year to convert from cyclosporin A to azathioprine or to continue on cyclosporin A. Prednisolone was increased twofold during the period of conversion, and there was a 3-week overlap period during which azathioprine and cyclosporin A were given. No grafts were lost due to rejection related to conversion, but 9 of the 33 patients who were randomized to convert experienced rejection episodes and 6 were returned to cyclosporin A. Conversion to azathioprine resulted in a drop in creatinine and improvement in blood pressure control. In the group randomized to stay on cyclosporin A, 6 patients had to be subsequently converted to azathioprine because of cyclosporin A toxicity in spite of well-controlled plasma levels. The creatinine levels after successful conversion remained stable whereas those of the patients continuing on cyclosporin A showed a progressive decline. We conclude that conversion from cyclosporin A to azathioprine can be achieved safely. Progressive deterioration in graft function with continuing cyclosporin A therapy does occur and should be taken as an indication for conversion. PMID- 2196061 TI - A review of magnetic resonance imaging: considerations for the dental practitioner. PMID- 2196062 TI - A historical review of UTDB. PMID- 2196063 TI - Prediction of salt sensitivity. AB - The overall prevalence of salt sensitivity was studied in 75 men stratified by diagnosis (hypertensive v normotensive) and race (black v white). All were studied in a crossover design employing a 200 mEq and 10 mEq Na/day. High salt led to a decrease in diastolic pressure for all groups (P less than .002). For systolic pressure, there was no salt effect on blood pressure across the whole group; however amongst the hypertensives, particularly the black hypertensives, high salt led to increases in systolic pressure (P less than .022). Obese patients were more likely to increase their systolic pressure in response to salt loading (P less than .05). The patients whose pressure increased on high salt were those who manifested less of a decrease in plasma levels of norepinephrine and renin in response to salt loading (both P less than .05). Systolic salt sensitivity was predicted with high statistical power (R = 0.689, P less than .00001) by a multiple regression equation employing: race; diagnosis; the change in renin and norepinephrine levels with diet; and the change in BP sensitivity to infused norepinephrine across the two diets. In view of the findings of increased norepinephrine, renin and diastolic pressure on low salt and in view of the particular physiological and epidemiological setting associated with systolic salt sensitivity, one wonders about the advisability of across-the-board recommendations of low salt diets for all hypertensive patients. PMID- 2196064 TI - Chloride ion plays an important role in sodium induced volume expansion in normal humans. AB - Eight normal women took part in a randomized crossover study to investigate the effect of dietary supplementation with 105 mEq sodium chloride (NaCl) for 3 days or equimolar sodium citrate (NaCit) after salt depletion. NaCit supplement induced greater urinary sodium and potassium excretions than did the NaCl supplement (197 +/- 10 v 107 +/- 19 mEq/3 days for sodium, P less than .01, 130 +/- 7 v 96 +/- 6 mEq/3 days for potassium, P less than .01, respectively) and less body weight gain (+0.6 +/- 0.1 v +1.6 +/- 0.1 kg, P less than .01). Suppressions of plasma norepinephrine, renin activity and aldosterone concentration were significantly smaller with NaCit than with NaCl supplement. We conclude that the anionic component of sodium salts may have some effects on renal sodium handling and modulates volume expansion and humoral factors. PMID- 2196065 TI - Effects of magnesium on changes in blood pressure and plasma aldosterone induced by angiotensin II. AB - This study examined the effects of magnesium on changes in blood pressure and plasma aldosterone concentration (PAC) elicited by angiotensin II in rats. The infusion of angiotensin II (0.1 nmol/kg/min) for 30 min increased mean arterial pressure (MAP) and PAC. Simultaneous infusion of magnesium sulphate (5 mumols/kg/min) attenuated the MAP elevation (157.0 +/- 5.2 (SE) v 141.6 +/- 3.5 mm Hg, P less than .01) and the increase in PAC (447 +/- 70 v 233 +/- 50 pg/mL, P less than .01) brought about by angiotensin II. These effects of magnesium were abolished when endogenous angiotensin II was suppressed by the administration of captopril, an angiotensin converting enzyme inhibitor. The results suggest that magensium may attenuate the biological actions of angiotensin II. PMID- 2196067 TI - Aesthetics and osseointegration. PMID- 2196066 TI - Moderate sodium restriction. PMID- 2196068 TI - Soft tissue management. An organized approach to treating the periodontal patient. PMID- 2196069 TI - Immortalization of hypothalamic GnRH neurons by genetically targeted tumorigenesis. AB - By genetically targeting tumorigenesis to specific hypothalamic neurons in transgenic mice using the promoter region of the gonadotropin-releasing hormone (GnRH) gene to express the SV40 T-antigen oncogene, we have produced neuronal tumors and developed clonal, differentiated, neurosecretory cell lines. These cells extend neurites, express the endogenous mouse GnRH mRNA, release GnRH in response to depolarization, have regulatable fast Na+ channels found in neurons, and express neuronal, but not glial, cell markers. These immortalized cells will provide an invaluable model system for study of hypothalamic neurosecretory neurons that regulate reproduction. Significantly, their derivation demonstrates the feasibility of immortalizing differentiated neurons by targeting tumorigenesis in transgenic mice to specific neurons of the CNS. PMID- 2196070 TI - The second phagocyte discussion meeting dedicated to the memory of David Flenley 1933-1989. PMID- 2196071 TI - Specific inhibition of phagosome-lysosome fusion in murine macrophages mediated by Salmonella typhimurium infection. AB - Phagosome-lysosome fusion in murine macrophages infected with S. typhimurium LT2 or S. typhi 1079 was investigated. Fusion of phagosome containing S. typhimurium LT2 with lysosome was markedly impaired, whereas S. typhi 1079 did not inhibit phagosome-lysosome fusion in murine macrophages. A similar inhibition of fusion was observed with LPS-deficient mutants of S. typhimurium LT2, suggesting that O antigens do not contribute to the inhibition of fusion. Phagosome-lysosome fusion in macrophages after ingestion of UV-killed S. typhimurium LT2 was much greater than that of live bacteria. Furthermore, treatment of S. typhimurium LT2 with streptomycin, an inhibitor of bacterial protein synthesis, caused an increase in the extent of phagosome-lysosome fusion. Therefore protein synthesis in live bacteria is probably required for the inhibition of phagosome-lysosome fusion. These results suggest that phagosome-lysosome fusion in murine macrophages is impaired by some product(s) of viable S. typhimurium LT2. PMID- 2196072 TI - Single maxillary central incisor in association with mid-line anomalies. AB - A single maxillary central incisor may occur as an isolated dental finding. However, it has also been reported to occur in association with autosomal dominant holoprosencephaly, in association with growth retardation with or without growth hormone deficiency and occasionally in association with other mid line developmental defects. Holoprosencephaly and pituitary dysfunction are two specific examples of mid-line defects and this report emphasises that other mid line defects may be associated with a single maxillary central incisor. We recommend that patients with this dental anomaly should be referred for a detailed medical examination. PMID- 2196073 TI - Badges of the dental profession. The International Organization for Standardisation. PMID- 2196074 TI - Uptake and binding of 3'-(3-cyano-4-morpholinyl)-3'-deaminoadriamycin and 3'-(4 morpholinyl)-3'-deaminoadriamycin in L5178Y lymphoblasts in vitro. AB - 3'-(3-Cyano-4-morpholinyl)-3'-deaminoadriamycin (CMA) and 3'-(4-morpholinyl)-3' deaminoadriamycin (MA) are analogues of Adriamycin, with altered cytotoxic activity. CMA is 100- to 1500-fold more cytotoxic than Adriamycin and possesses unique DNA crosslinking activity. Intact MA does not crosslink DNA and has a cytotoxicity equivalent to Adriamycin, but it retains its activity in anthracycline-resistant cells. In this study, uptake and binding of [3H]CMA and [3H]MA in L5178Y lymphoblasts were examined. Both CMA and MA were rapidly taken up by cells at 37 degrees C and concentrated almost exclusively in the nucleus. All of the intracellular MA was TCA-soluble, but only 45% of this drug effluxed from the cells by 4 hr. More than 50% of CMA in the cells was TCA-insoluble, and approximately 40% effluxed from the cells by 4 hr through loss of the TCA-soluble fraction. CMA differed from other alkylating agents in that more than 97% of the bound drug was associated with DNA. The bound drug was partially lost from the DNA by a process that may have involved DNA repair. PMID- 2196075 TI - Rothmund-Thomson syndrome: a report of two patients and a review of the literature. AB - Two siblings with poikiloderma, short stature and other abnormalities are described. They were originally reported as having Morquio syndrome; subsequently, mucopolysaccharidosis was excluded biochemically and they were classified as 'a newly recognized syndrome of connective tissue dysplasia'. It is now clear that their disorder is the Rothmund-Thomson syndrome (RTS). PMID- 2196076 TI - A consensus report: cyclosporin A therapy for psoriasis. PMID- 2196077 TI - Renal side-effects of cyclosporin A with special reference to autoimmune diseases. AB - At therapeutic drug levels, the functional changes which occur are a reduction of glomerular filtration rate and renal plasma flow. At higher doses, morphological changes develop which may result, particularly in severe cases, in acute or chronic renal failure. The threshold for the development of irreversible vascular interstitial lesions mainly depends on the increment of serum creatinine, age and drug dosage or drug blood level. Based on the experience with cyclosporin A (CyA), the following recommendations have been made for its clinical use, especially in patients with autoimmune diseases. The initial dose should not exceed 5 mg/kg body weight and the dose should be reduced if blood CyA levels are over 250 ng/ml; in addition, a dose reduction is recommended if serum creatinine values exceed 30% of pre-treatment values or if other signs of CyA toxicity, such as hepatotoxicity or hypertension, are found. Strict adherence to these suggestions should allow treatment of patients for prolonged periods without irreversible morphological lesions. PMID- 2196078 TI - Side-effects of psoralen photochemotherapy (PUVA). AB - Although psoralen photochemotherapy (PUVA) is one of the most effective forms of therapy for psoriasis, the risk of potential long-term side-effects is, as yet, not clearly determined. Chronic degenerative and pigmentary skin changes similar to those of chronic solar exposure occur after long-term PUVA treatment; PUVA also causes non-melanoma skin cancers in man, although there is, as yet, no consensus as to what cumulative phototoxic PUVA dose is carcinogenic. Long-term multicentre studies from the U.S.A. indicate a definite risk of squamous cell carcinoma for long-term PUVA-treated patients, whereas European studies reveal no overall increase in skin cancers in similar patients except for those exposed to other carcinogens. Assignment to PUVA should be based on the risk:benefit ratio for the individual patient. Careful patient selection is therefore mandatory and should be limited to those who can be monitored and controlled by informed, competent and conscientious physicians. PMID- 2196079 TI - Methotrexate side-effects. AB - Methotrexate is by far the most widely used cytotoxic drug in psoriasis. Treatment requires normal kidney, liver and bone-marrow function, and pregnancy and alcohol abuse are absolute contraindications. Serious toxic reactions are recognized, but can be avoided if the drug is used correctly. The most important side-effects are haematopoietic and hepatotoxic. It is well established that long term methotrexate can induce liver damage which, in a number of patients, may lead to fibrosis or cirrhosis. Recent studies have, however, documented that the methotrexate-induced liver cirrhosis is not aggressive. Interaction can occur with a number of drugs; serious problems in particular may arise with concomitant use of sulphonamides and salicylates. The recommended guidelines for methotrexate use in psoriasis should be followed and patients given clear instructions. PMID- 2196080 TI - Efficacy of cyclosporin A in psoriasis: a summary of the United States' experience. AB - Since its discovery in 1972, cyclosporin A (CyA) has been widely used in the experimental treatment of multiple inflammatory diseases considered to be of immune-mediated aetiology. In dermatology, oral CyA is most effective in the treatment of psoriasis and has been used successfully for plaque-type, pustular and erythrodermic forms of the disease. While dosages ranging from 1 to 14 mg/kg/day have been used, a starting dose of 4 mg/kg/day gives a rapid response with few side-effects. Nephrotoxicity remains the greatest concern in long-term use of the drug. Although intralesional CyA has proven effective in psoriasis, topical preparations have not. It is hoped that future research will provide effective topical formulations of CyA which are efficacious without the risks inherent in systemic administration. PMID- 2196081 TI - Oral cyclosporin A in the treatment of psoriasis: an overview of studies performed in The Netherlands. AB - This is a review of the clinical studies performed so far in The Netherlands of the treatment of psoriasis with cyclosporin A (CyA), a selective immunosuppressive drug that has caused a major breakthrough in transplant medicine. Data derived from a double-blind placebo-controlled study (5 mg/kg/day of CyA), dose-finding studies (2.5 mg vs 5 mg/kg/day and 1 mg, 2 mg or 3 mg/kg/day), and long-term treatment of chronic plaque-type psoriasis (1.1-7.2 mg/kg/day) suggest an initial starting dose of 3 mg/kg/day irrespective of the severity of the disease. Long-term treatment brought about dose- and time dependent (reversible) side-effects, including renal dysfunction and hypertension. Efforts to reduce the dose included concomitant administration of drugs known to have anti-psoriatic efficacy. Only combination with topical steroids appeared to add to the clinical efficacy of CyA, but did not allow a dose reduction sufficient to restore renal function. Dose reduction through intermittent treatment, however, postponed exacerbations sufficiently to permit at least partial normalization of serum creatinine levels. A similar effect was seen in the treatment of pustular palmoplantar psoriasis, which responded to doses of 1.1-6.1 mg/kg/day. PMID- 2196082 TI - Efficacy of low-dose cyclosporin A in psoriasis: results of dose-finding studies. AB - The efficacy of cyclosporin A (CyA) in severe psoriasis was analysed in 457 adult patients included in five European multicentre dose-finding studies. Initial CyA doses were 1.25 mg/kg/day in 33 patients, 2.5-3 mg/kg/day in 285 and 5 mg/kg/day in 139. After 3 months of treatment, the reduction of the Psoriasis Area and Severity Index (PASI) score was 35 +/- 6% with 1.25 mg/kg/day of CyA, 57 +/- 2% with 2.5 mg or 3 mg/kg/day and 86 +/- 2% with 5 mg/kg/day (P less than 0.001). The rates of success, defined by a PASI score reduction greater than or equal to 75% or a score less than or equal to 8, were 24%, 52% and 88%, respectively. There were no differences in age, initial severity or duration of psoriasis. The improvement was maintained for 9 months or more in the majority of patients receiving continuous CyA therapy. PMID- 2196083 TI - Cyclosporin A in atopic dermatitis. AB - Over the past 10 years, oral cyclosporin A (CyA) has been used to treat a range of inflammatory and immunologically mediated dermatological conditions, but only psoriasis has been shown to be responsive in double-blind, controlled trials. Thirteen patients with severe atopic dermatitis were treated for up to 31 months. Ten patients had a good response, one patient a moderate response and two a slight response. In two of these patients, CyA was withdrawn after more than 2 years of continuous treatment because of increasing plasma creatinine levels. Cyclosporin A appears to be useful in the treatment of severe, therapy-resistant atopic dermatitis, but careful monitoring of side-effects and dose adjustments are required. PMID- 2196084 TI - Side-effect profile of cyclosporin A in patients treated for psoriasis. AB - This is a review of the side-effects of cyclosporin A (CyA) in patients with severe psoriasis; renal dysfunction and hypertension are discussed elsewhere. In particular, paraesthesia, hypertrichosis, gingival hyperplasia and gastrointestinal disorders may occur, but are generally transient, mild-to moderate in severity and only rarely require discontinuation of CyA. Infections are not a problem. As expected with an immunosuppressive drug, there is the possible risk of tumour development, particularly squamous cell carcinomas. However, these skin malignancies developed almost exclusively in patients previously treated with PUVA and/or methotrexate. The few lymphoproliferative disorders regressed spontaneously on discontinuation of the drug. Whether the isolated cases of solid tumours were CyA-related is not known. Apart from a raised serum creatinine, an important indicator of renal dysfunction, the laboratory abnormalities included hypomagnesaemia, hyperkalaemia, increased uric acid, changes in liver function tests, and fluctuations in the serum cholesterol and triglyceride levels. Although most of these changes were not clinically relevant, laboratory monitoring of patients with psoriasis treated with CyA is essential. PMID- 2196085 TI - Renal function and blood pressure in psoriatic patients treated with cyclosporin A. AB - Serum creatinine and blood pressure were measured in patients who had severe psoriasis and who were treated with cyclosporin A (CyA) in initial doses of 1.25 mg (n = 34), 2.5 or 3 mg (n = 314), or 5 (n = 215) mg/kg/day. Of the 563 patients involved, 201 were treated for more than 3 months, and 100 received CyA continuously for 12 months or more. Sixty-eight additional patients were included as controls and received placebo (n = 42) or etretinate (n = 26). At doses of 2.5 and 5 mg/kg/day, CyA induced slight but significant dose-dependent increases in serum creatinine and blood pressure. Creatinine increases of 50% or more over baseline values were detected in 4% of the patients receiving 2.5 mg/kg/day and in 13% of those receiving 5 mg/kg/day. After an initial rise during the first weeks of treatment, mean creatinine level remained stable over 1 year provided that the CyA dose was reduced whenever creatinine levels increased by 30% or more over baseline. The incidence of hypertension was 10.6% and did not vary whether the CyA dose was 2.5 or 5 mg/kg/day. The first elevated blood pressures were recorded early after starting CyA therapy (median: 1 month). However, 3 months after stopping treatment, the increases in creatinine as well as in blood pressure were reversible and the levels did not significantly differ from baseline values. PMID- 2196086 TI - Calcium-dependent fusion of the plasma membrane fraction from human neutrophils with liposomes. AB - A cell-free assay monitoring lipid mixing was used to investigate the role of Ca2+ in neutrophil membrane-liposome fusion. Micromolar concentrations of Ca2+ were found to directly stimulate fusion of inside-out neutrophil plasma membrane enriched fractions (from neutrophils subjected to nitrogen cavitation) with liposomes (phosphatidylethanolamine:phosphatidic acid, 4:1 molar ratio). In contrast, right-side-out plasma membranes and granule membranes did not fuse with liposomes in the presence of Ca2+. Similar results were obtained with two different lipid mixing assays. Fusion of the neutrophil plasma membrane-enriched fraction with liposomes was dependent upon the concentration of Ca2+, with threshold and 50% maximal rate of fusion occurring at 2 microM and 50 microM, respectively. Furthermore, the fusion was highly specific for Ca2+; other divalent cations such as Ba2+, Mg2+ and Sr2+ promoted fusion only at millimolar concentrations. Red blood cell (RBC) membranes were used in control studies. Ca2(+)-dependent fusion did not occur between right-side-out or inside-out RBC vesicles and liposomes. However, if the RBC-vesicles were exposed to conditions which depleted spectrin (i.e., low salt), then Ca2(+)-dependent fusion was detected. Other quantitative differences between neutrophil and RBC membranes were found; fusion of liposomes with RBC membranes was most readily achieved with La3+ while neutrophil membrane-liposome fusion was most readily obtained with Ca2+. Furthermore, GTP gamma S was found to enhance Ca2(+)-dependent fusion between liposomes and neutrophil plasma membranes, but not RBC membranes. These studies show that plasma membranes (enriched fractions) from neutrophils are readily capable of fusing with artificial lipid membranes in the presence of micromolar concentrations of Ca2+. PMID- 2196087 TI - Cell-free synthesis of mycolic acids in Mycobacterium aurum: radioactivity distribution in newly synthesized acids and presence of cell wall in the system. AB - Distribution of radiolabelling in different parts of the newly synthesized mycolic acids, by a cell-free system from Mycobacterium aurum previously described, is examined, [1-14C]acetate being the precursor. By oxidation cleavage of mycolic acids and examination of the fragments, it was shown that acetate was not uniformly incorporated into the molecule: the methyl terminal part was not labelled, while the central fragments--between unsaturations or between oxygenated functions (oxo or ester) and unsaturations--presented the major part of radioactivity, suggesting the elongation of a preformed compound that the cell free extract was unable to synthesize. Moreover, the side-chain R2-CH2-COOH was only weakly labelled compared to the central fragments. Since non-hydroxylated fatty acids were not synthesized by the system, it is suggested that de novo C18 fatty acids may be elongated with C2 units by the cell-free extract into C22 fatty derivative, only a low level of labelling being recorded (two C2 units for all the molecule). A scheme is proposed to summarize the main results. Identification of meso-DAP which is a characteristic amino-acid of the peptidoglycan in Actinomycetes and analysis of the profiles of total fatty esters, demonstrated that the cell-free extract is partly constituted by fragments of the cell wall as has already been noticed by examination of micrographs of the extract. PMID- 2196088 TI - [Valine substitution]. AB - The review deals with analysis of the literature data concerning the importance of valine substitution in certain proteins, namely p21 ras and hemoglobin. A model of the active site of p21 protein is discussed in the light of GTPase activities alterations as a result of monoaminoacid substitution in conservative sites of p21 protein. The established relationship between some forms of transformation and Plasmodium falciparum malaria on the molecular level is shown in a new aspect. The widespread opinion that Hb S is valid as the means of malaria resistance is questioned in terms of new molecular data. PMID- 2196089 TI - Progress toward human gene therapy. PMID- 2196090 TI - Human serum megakaryocyte colony-stimulating activity appears to be distinct from interleukin-3, granulocyte-macrophage colony-stimulating factor, and lymphocyte conditioned medium. AB - Sera from patients with bone marrow megakaryocyte aplasia are a rich source of megakaryocyte colony-stimulating activity (Meg-CSA). Other biologic materials exhibiting Meg-CSA include phytohemagglutinin-stimulated human lymphocyte conditioned medium (PHA-LCM), recombinant interleukin-3 (IL-3), and recombinant granulocyte macrophage colony-stimulating factor (GM-CSF). Neutralizing antisera to both recombinant IL-3 and GM-CSF were used to evaluate the relationship among these sources of Meg-CSA. Varying dilutions of IL-3 and GM-CSF antisera were tested in plasma clot cultures of normal human peripheral blood megakaryocyte progenitors optimally stimulated by either IL-3 (1 U/mL), GM-CSF (1 U/mL), PHA LCM (2.5% to 5% vol/vol), or aplastic human serum (10% vol/vol). IL-3 antiserum at dilutions up to 1/2,000 totally abrogated megakaryocyte colony growth stimulated by IL-3. A 1/500 dilution of GM-CSF antiserum completely eliminated GM CSF-induced megakaryocyte colony development. A combination of anti-IL-3 and anti GM-CSF, each at a 1/500 dilution, inhibited all megakaryocyte colony growth stimulated by optimal concentrations of IL-3 and GM-CSF together. There was no neutralizing crossreactivity between the IL-3 and GM-CSF antisera. At maximally neutralizing concentrations, IL-3 antiserum inhibited 66% of the megakaryocyte colony growth stimulated by PHA-LCM. Residual megakaryocyte colony growth was eliminated by the addition of a 1/500 dilution of anti-GM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196091 TI - Regulation of proto-oncogene and tumor necrosis factor gene expression by ethanol in HL-60 myeloid leukemia cells. AB - Previous studies have shown that certain low molecular weight polar solvents downregulate c-myc gene expression and induce terminal differentiation of human HL-60 myeloid leukemia cells. We have examined the effects of ethanol on gene expression in this cell line. The results show that while ethanol induces a more differentiated phenotype, this agent has little effect on the self-renewal capacity of HL-60 cells. Ethanol treatment was also associated with a concentration-dependent and transient downregulation of c-myc transcripts. Similar effects were observed for c-myb mRNA levels. The results further show that ethanol exposure is associated with induction of tumor necrosis factor gene expression. These findings indicate that ethanol induces changes in specific gene expression during non-terminal differentiation of HL-60 cells. The clinical effects of this agent could thus be related to altered patterns of gene expression in hematopoietic or other cells. PMID- 2196092 TI - Expression of platelet glycoprotein Ib by cultured human megakaryocytes: ultrastructural localization and biosynthesis. AB - Glycoprotein Ib (GPIb), the receptor for von Willebrand factor, is a two-chain member constituent of the platelet/megakaryocytic lineage. Studies on its expression have been hampered by the difficulties in obtaining purified megakaryocytes in a sufficient number. We report a suspension liquid culture procedure that allowed isolation of more than 1 x 10(6) megakaryocytes with a purity ranging from 3% to 88% from the blood of patients with chronic myeloid leukemia, from fetal liver or from normal human bone marrow. GPIb was detected on the plasma membrane of all maturing megakaryocytes and also of promegakaryoblasts devoid of demarcation membranes. GPIb was detected on demarcation membranes of maturing megakaryocytes but was absent from all other organelles, including alpha granules. Biosynthesis of 35S-methionine labeled megakaryocytes showed that GPIb with similar electrophoretic mobility to the platelet molecule was synthesized and that it was also composed of two chains, since its molecular weight shifted in reducing conditions from 170 Kd to 145 Kd. The beta chain remained undetectable after methionine metabolic labeling, but it was immunoprecipitated after 3H-leucine metabolic labeling, confirming that this subunit is devoid of methionine. GPIb was associated with GPIX, as it is in platelets, since anti-GPIb antibodies coprecipitated a 17 Kd polypeptide. PMID- 2196093 TI - Central pain. PMID- 2196094 TI - Aerosol inhalers. PMID- 2196095 TI - The penicillins today. PMID- 2196096 TI - Experiences of a battalion medical officer in the retreat to Dunkirk: III. PMID- 2196097 TI - ABC of major trauma. Initial assessment and management--II: Secondary survey. PMID- 2196098 TI - Nebulized amphotericin B as prophylaxis against invasive aspergillosis in granulocytopenic patients. AB - The efficacy of inhaled amphotericin B in prevention of invasive aspergillosis in patients with granulocytopenia (granulocytes less than 0.5 X 10(9)/l for greater than 10 days) was investigated over a 12-month period. Amphotericin B prophylaxis was administered twice daily for the period of granulocytopenia to 34 patients who were at risk during 144 episodes of granulocytopenia. The cohort at risk was compared with historical controls. In the 2 years prior to institution of prophylaxis, 14 patients (11.4% of those at risk) developed invasive aspergillosis. All cases occurred whilst the patients were nursed on the open wards. Aspergillosis did not develop in 25 granulocytopenic patients nursed in single rooms with HEPA filtration. Since institution of prophylaxis, there have been no cases of invasive aspergillosis. These data suggest that nebulized amphotericin B may be useful in preventing invasive pulmonary aspergillosis in granulocytopenic patients, especially those nursed on the open wards, and warrants further investigation. PMID- 2196100 TI - Seventy-five years of military dentistry in Canada. PMID- 2196099 TI - Osteoclasts and a small population of peripheral blood cells share common surface antigens. AB - Several methods have been tried to identify mononuclear osteoclast precursors. We used a panel of 13 osteoclast-recognizing monoclonal antibodies (mabs) for the identification of osteoclast precursor cells from the bone, bone marrow, and peripheral blood of egg laying hens. Almost all mabs stained some mononuclear cells in the bone. Seven mabs recognized few mononuclear cells in the bone marrow and five mabs gave the positive immunofluorescence reaction in the white blood cell fraction. Possible immediate osteoclast precursor cells differing from osteoclasts in their densities were identified in the bone. Three mabs (K38, K52, and K70) stained the same amount of mononuclear cells (2.6-3.4%) enriched in Percoll density centrifugation. Of the monoclonal antibodies that recognized few cells in blood, K41 stained only osteoclasts. K47 and K52 also recognized some mononuclear cells in the bone marrow. Other monoclonal antibodies K51 and K70 were more unspecific, since they stained cells derived from other tissues. Blood cells detected with these different monoclonal antibodies were negative for tartrate-resistant acid phosphatase (TRAP). On the basis of our results, we suggest that there is in the blood a specific TRAP-negative cell population, which is a good candidate for osteoclast precursor. PMID- 2196101 TI - Cyanoacrylates in dentistry: a review of the literature. AB - A discussion of the uses of cyanoacrylates in dentistry and an update of the literature have been presented. The biocompatibility and histotoxicity of this material has been considered. Studies have shown that the higher homologues are more tissue compatible than the lower. Local tissue responses show histiocytic proliferation and formation of giant cells. The foreign body cell responses are more pronounced when cyanoacrylate is placed deep in an extraction socket and under tissue flaps when compared with superficial application of the adhesive. While cyanoacrylate-induced neoplasia has been a concern, long-term studies are needed to provide more light on this and other histotoxicity problems. Cyanoacrylates are bacteriostatic for many bacterial types. It is apparent that cyanoacrylates could have some useful clinical applications in periodontics and oral surgery. They are very effective tissue adhesives and their use as a nonsuturing material would provide many advantages. Research indicates that use should be restricted to superficial application. The hemostatic properties of this material have been confirmed in virtually every study, but it should be used judiciously for this purpose. Several other potential periodontal and oral surgery applications were considered. It is expected that future research will examine new applications of the material for surgical use. Preventive and restorative applications were also discussed, but unfortunately, these have not met with much success. Newer techniques and materials seem superior in this aspect of dentistry. Possible application may eventually be shown in the desensitizing of dentin and cementum. Endodontic applications were also considered. While most studies indicate that cyanoacrylate would make an acceptable pulp-capping material, calcium hydroxide is still the material of choice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196102 TI - Commonly prescribed medical drugs and their significance in dental therapy. Part I--The antibiotics. AB - An analysis of Tables I and II reveals that the 20 drugs most frequently prescribed by family practitioners may be classified into 10 therapeutic categories. The antibiotics constitute the numerically largest group. The medical use, adverse reactions, and dental significance of these antibiotics have been described. The remaining drugs will be discussed using a similar format in subsequent papers. PMID- 2196103 TI - Endodontics and the elderly patient--management considerations. PMID- 2196104 TI - Endodontics, past, present, and future? PMID- 2196105 TI - Dental health status and treatment needs of elderly residents of Edmonton, Alberta. AB - The oral health of 140 independent elderly volunteers, selected from different sections of Edmonton, Alberta, was assessed in conjunction with their nutritional and medical status, in an attempt to evaluate the dental needs of this population. Dental caries was assessed using WHO standards and the CPITN was used in assessing periodontal and gingival health needs. The mean age of the participants was 70.9 +/- 2.6 years. The average time since they had last seen a dentist was 3.0 +/- 6.2 years. Twenty-six percent of the group were edentulous and wore full dentures. An evaluation of denture hygiene and retention showed that 53 per cent of all maxillary and 57 per cent of all mandibular appliances exhibited poor hygiene; 33 per cent and 54 per cent, respectively, had problems with retention and/or occlusion. Only 12 per cent of the group exhibited any sort of mucosal pathology, all of which was related to ill fitting dentures. The total population had a mean of 15.0 +/- 11.1 teeth, only 0.5 of these were decayed, while 8.9 were restored. CPITN scores taken from a total of 511 sextants with standing teeth showed that 16 per cent of the group exhibited bleeding upon probing, 29 per cent had calculus, 13 per cent exhibited pocketing, while 3.6 per cent had deep pockets. Sixty-seven per cent of the population required dental treatment, none of whom needed emergency intervention. Over 49 per cent of the dentate population could benefit from prophylaxis; 16 per cent required more definitive periodontal treatment. Forty-five per cent of the denture population required treatment. PMID- 2196106 TI - Occlusal adjustment. AB - Occlusal adjustment is a misunderstood and underutilized procedure that is often indicated in the management of occlusion-related disorders. To clarify the confusion extant about occlusal adjustment and to encourage its use, when appropriate, this paper examines optimal, normal and abnormal occlusions, classifies abnormal occlusions according to morphological and functional characteristics and treatment needs, and presents a rationale for occlusal adjustment based on these concepts. Differences between occlusal adjustment, occlusal equilibration and selective grinding are discussed, occlusal interferences are defined and described and the indications and contraindications for occlusal adjustment are presented. PMID- 2196107 TI - A randomized study comparing two regimens of neoadjuvant and adjuvant chemotherapy in multimodal therapy for locally advanced head and neck cancer. AB - Two regimens of neoadjuvant chemotherapy for previously untreated patients with locally advanced head and neck cancer were compared with the goal of identifying a regimen with a greater than 50% complete response (CR) rate. Patients with a performance status of 0 to 2 and normal end-organ function were randomized to receive either four cycles of neoadjuvant methotrexate, cisplatin, and continuous infusion 5-fluorouracil (5-FU) (MPF) (arm A), or four cycles of bleomycin, cisplatin, and methotrexate (PBM) alternating with cisplatin and 5-FU (PF) (arm B). Patients with a performance status of greater than 2 or a carbon monoxide diffusion capacity of less than 50% of the predicted value were assigned to the arm A regimen but were analyzed separately (arm C). Local therapy consisted of surgery (for patients with resectable disease) or radiation therapy followed by two cycles of adjuvant chemotherapy with the regimen that was administered initially. Of the 42 patients who were evaluated, 16 were randomized to arm A, 13 to arm B, and 13 to arm C. The clinical CR rate was 19% on arm A (95% confidence interval, 0% to 38%), 39% on arm B (95% confidence interval, 12% to 66%) (P = 0.41), and 54% on arm C (95% confidence interval, 27% to 81%). At a median follow up time of 35 months, the 2-year actuarial survival rate was 61% on arm A, 69% on arm B (the P value was not significant), and 38% on arm C. The 2-year survival rate for all 42 patients who were treated was 57% and the median survival time was 31 months. Toxicities of neoadjuvant chemotherapy on all arms consisted of mild to moderate myelosuppression and renal toxicity. The incidence of moderate to severe mucositis was significantly higher on arm A than arm B (P = 0.02). Two cycles of adjuvant chemotherapy were administered to only 11 of 42 patients due to patient refusal or cumulative toxicity. In conclusion, both neoadjuvant chemotherapy regimens resulted in similar response and survival rates, but mucositis was more severe with arm A. However, since neither regimen was likely to cause a CR rate of greater than 50%, this study was closed to further patient accrual. PMID- 2196108 TI - Evaluation of the worth of corynebacterium parvum in conjunction with chemotherapy as adjuvant treatment for primary breast cancer. Eight-year results from the National Surgical Adjuvant Breast and Bowel Project B-10. AB - During the 1970s, information obtained from animal tumor models and from patients with a spectrum of solid tumors indicated the worth of a variety of immunostimulating agents. These findings provided a biological and clinical rationale for conducting randomized trials to evaluate the worth of those agents. Consequently, in May 1977 the National Surgical Adjuvant Breast and Bowel Project (NSABP) implemented a randomized trial to determine whether Corynebacterium parvum (C. parvum, CP) plus chemotherapy would be more effective than chemotherapy alone in prolonging the disease-free survival (DFS) and survival (S) of patients with primary operable breast cancer and positive axillary nodes. The results of that trial through 8 years of follow-up fail to indicate that treatment with CP used in conjunction with l-phenylalanine mustard (L-PAM) plus 5 fluorouracil (PF) results in a better DFS and S than that observed after chemotherapy alone. Use of the immunomodulator has instead resulted in a poorer, but not statistically significant, outcome. Despite adjustments made to account for any imbalance in distribution of prognostic factors between the two treatment groups and despite considering treatment compliance as a factor, the unfavorable outcome persisted. A high incidence of fever and chills was associated with the administration of CP. The administration of hydrocortisone before each CP treatment reduced the frequency of those and other systemic effects. The failure to demonstrate a benefit from CP is in keeping with the failure of other nonspecific stimulating agents to contribute to the creation of a new paradigm for the treatment of breast cancer. PMID- 2196109 TI - Immunophenotype profile of childhood medulloblastomas and supratentorial primitive neuroectodermal tumors using 16 monoclonal antibodies. AB - Immunophenotype analysis of 17 childhood medulloblastoma (MED) and supratentorial primitive neuroectodermal tumors (SPNET) was performed on frozen sections using 16 monoclonal antibodies (MoAb) with the biotin-streptavidin alkaline phosphatase immunohistochemical technique. Neuroectodermal associated antigens, reacting with MoAb UJ13/A, UJ127.11, UJ167.11, and UJ223.8 were detected on greater than 10% of the cells in 15 of 17 MED/SPNET. Thy-1 was present on 14 of 17 tumors and absent on two of three SPNET. Neuronal (NF) and glial (GFAP) differentiation markers were evaluated. NF-H was demonstrated in 15 of 17, NF-M in six of 17 and NF-L in one of 17 tumors; GFAP was positive in nine of 17 patients. In nine of 17 MED/SPNET both proteins were present within the same tumor. Common leukocyte antigen was demonstrated on greater than 50% of the cells in four of 14 tumors as were shared tumor/leukocyte markers using monoclonal antibodies Thy-1, PI153/3, UJ308. The most frequent MED immunophenotype analysis was UJ 13/A+, UJ 127.11+, UJ 167.11+, UJ223.8+, PI 153/3+, A2B5+, GFAP+, NF-H+, and CLA-, NF-M-, NF-L-, 215 , 275-, 282.1-. The authors conclude that MED and SPNET are heterogeneous for expression of 16 markers and have similar immunophenotype analysis profiles, supporting the concept of their common, neuroectodermal origin. Common leukocyte antigen on both tumor cells and leukocytes precludes identification of tumor infiltrating leukocytes using monostaining techniques. PMID- 2196110 TI - Association of point mutation in c-Ki-ras oncogene in lung adenocarcinoma with particular reference to cytologic subtypes. AB - The correlation between clinicopathologic findings and point mutation in codon 12 of c-Ki-ras gene was examined in primary lung adenocarcinomas using polymerase chain reaction and oligonucleotide hybridization techniques. The mutation was detected in ten of 67 cases (15%). Microscopically, mutation-positive cases revealed a tendency to be well differentiated (P less than 0.01). Especially, the incidence of the mutation-positive cases was significantly higher in goblet cell type (three of four) than in other types (five of 56) (P less than 0.001). None of 21 cases of pure Clara cell type showed the mutation (P less than 0.05). The mutation was detected frequently in tumors with no lymph node metastasis (P less than 0.05), with larger tumor size (P = 0.01), and T2 cases (P less than 0.01). Cigarette smoking was not always a contributing factor for mutation. This study revealed that the point mutation of c-Ki-ras codon 12 in lung adenocarcinoma has been associated with the cytologic subtype. PMID- 2196111 TI - Ras oncogene expression and progression in intraepithelial neoplasia of the uterine cervix. AB - To examine the correlations between ras oncogene expression and the development of cervical cancer, the authors studied the reactivity of cervical intraepithelial neoplasia (CIN) and microinvasive lesions of the human uterine cervix by using anti-ras p21 mouse monoclonal antibody rp35. The frequency of positive p21 staining increased with increased grades of malignancy from 17.9% in CIN 1 to 28.9% in CIN 2 and 53.9% in CIN 3, whereas in microinvasive carcinoma it was 50.0%. Furthermore, ten cases of lesions that regressed during a 1-year follow-up period were positive for ras p21 in 20% of cases, but 14 cases of lesions that progressed and developed into higher graded lesions during the 2- to 5-year follow-up period had a 50.0% rate of positive p21 staining. It was concluded that ras oncogene product p21 correlates with the early phase of carcinogenesis of squamous cells of the uterine cervix. PMID- 2196112 TI - Report of an unusual small lymphocytic B-cell lymphoma selectively involving the B-zone of lymph node. AB - Selective involvement of the B-cell compartment of lymph node by B-cell malignant lymphomas is an occasional finding related to early phases of lymph node infiltration. The authors have observed a unique case of diffuse small lymphocytic lymphoma that consisted of immunohistologically and genotypically proven B-clonal population exhibiting a repetitive pattern of infiltration in three lymph node samples obtained from the patient during a 9-year period. This pattern consisted of a selective and complete replacement of the B-areas with disappearance of follicles and widening of the medullary cords, an expanded T zone showing features consistent with dermatopathic lymphadenitis and well preserved sinuses. Clinically, multiple involved sites at presentation (lymph nodes, spleen, skin, bone marrow, and peripheral blood) and during the 9-year follow-up (testis) were detected, and the disease was associated with a relative indolent course like other low-grade lymphomas. The phenotypic profile of lymphoma cells studied by immunoperoxidase method, and by single-labeling and double-labeling flow cytometric analyses (SIg+, K+, LN2+, MB1+, MB2+, HLA-DR+, CD 9+, CD19+, CD 20+, CD 21+, CD 22+, CD 24+, Leu 8+, CD 5-, CD 10-, CD 11b-, CD 11c , CD 25-, CD 38-, PCA-1-, FMC-7-, CD 23-) was consistent with a B-cell proliferation at an intermediate stage of differentiation but distinct from other well-defined B-cell neoplasms. Whether such unique B-zone pattern was due to an intrinsic property of this lymphoma or it is to be related to the coexisting reactive T-zone expansion remains controversial. PMID- 2196113 TI - Clinically isolated mandibular relapse in childhood acute leukemia. AB - With improved methods for preventing extramedullary relapse in the leptomeninges and gonads, the problem of clinically isolated relapse at other sites has become more significant. The authors report here two children with acute leukemia who developed mandibular relapse while in complete hematologic remission. One had been off chemotherapy for acute lymphoid leukemia for 2.5 years. The other child is apparently the first patient with promyeloid morphologic features to experience relapse at this site. Both children are in second complete remission and off treatment after local radiation therapy and second courses of chemotherapy. Review of these two and five previously reported isolated mandibular relapses in childhood leukemia indicate that they are usually delayed until after cessation of therapy. Treatment with radiation and combination chemotherapy can result in long remission and possibly cure. PMID- 2196114 TI - Thermal response of oncogene-transfected rat cells. AB - Rat embryo cells or Rat-1 fibroblasts were transfected with either an activated c myc or a c-Ha-ras from the T24/EJ bladder carcinoma, or they were cotransfected with both. A gene conferring neomycin or hygromycin resistance was also cotransfected so that independent cell lines could be selected by growth in medium containing the antibiotic. Certain isolates from cells transfected with only one type of oncogene were further transformed by exposure to 600 cGy of 250 kVp X-rays. Successful transfection and transformation were characterized by altered morphology, increased plating efficiency, shorter doubling time, longer life span, foci formation, anchorage-independent growth, and Southern and Northern hybridization analysis. The thermal response of these cells at different stages of oncogenic transformation was examined by exposing exponentially growing cells to 45 degrees C for 0 to 45 min and measuring cellular survivals using colony formation assay. We found that cells transfected with myc oncogene, singly or in combination with ras, were more sensitive to thermal stress. Aside from that, the cells' thermal sensitivity was not affected by the degree or the nature of transformation. PMID- 2196115 TI - In vitro biotransformations of tetrachloro(d,l-trans)-1,2 diaminocyclohexaneplatinum(IV) (tetraplatin) in rat plasma. AB - The in vitro biotransformation of tetrachloro(d,l-trans)-1,2, diaminocyclohexaneplantinum(IV) (tetraplatin) in the plasma of Fischer 344 rats were studied by the two-column high-performance liquid chromatography technique described previously (Mauldin et al., Cancer Res., 48: 5136-5144, 1988). The reduction of tetraplatin to dichloro(d,l-trans)-1,2 diaminocyclohexaneplatinum(II) [PtCl2(dach)] was extremely rapid. From experiments with diluted plasma, it was possible to estimate a t1/2 for tetraplatin of approximately 3 s at 37 degrees C in undiluted plasma. By titrating with N-ethylmaleimide, it was possible to show that sulfhydryl groups were responsible for 70-80% of the total reducing potential of plasma. The rapid reduction of tetraplatin to PtCl2(dach) was followed by slower substitution reactions involving the chloro ligands of PtCl2(dach). The t1/2 for PtCl2(dach) in plasma at 37 degrees C was 1.5 h. The monoaquamonochloro complex was an important biotransformation product at early times, reaching 10 to 12% of the total platinum present from 15 min to 2 h, when it was gradually replaced with more stable biotransformation products. Three major stable biotransformation products accumulated in the plasma. One of these biotransformation products was identified as the Pt(methionine)(dach) complex. The other two were tentatively identified as the Pt(cysteine)(dach) or Pt(ornithine)(dach) complex and the Pt(urea)(dach) or Pt(citrato)(dach) complex on the basis of coelution in two different high-performance liquid chromatography separation systems. These biotransformation products could play a role in tetraplatin effectiveness and/or toxicity. PMID- 2196116 TI - Interleukin 1-induced augmentation of experimental metastases from a human melanoma in nude mice. AB - This study has examined the effect of the cytokine interleukin 1 (IL-1) on metastasis formation by the human melanoma A375M in nude mice. We have found that human recombinant IL-1 beta (a single injection greater than 0.01 micrograms per mouse i.v. given before tumor cells) induced an augmentation of experimental lung metastases from the A375M tumor cells in nude mice. This effect was rapidly induced and reversible within 24 h after IL-1 injection. A similar effect was induced by human recombinant IL-1 alpha and human recombinant tumor necrosis factor, but not by human recombinant interleukin 6. 5-[125I]odo-2'-deoxyuridine radiolabeled A375M tumor cells injected i.v. remained at a higher level in the lungs of nude mice receiving IL-1 than in control mice. In addition, IL-1 injected 1 h, but not 24 h, after tumor cells enhanced lung colonization as well, thus suggesting an effect of IL-1 on the vascular transit of tumor cells. These findings may explain the observation of enhanced secondary localization of tumor cells at inflammatory sites and suggest that modulation of secondary spread should be carefully considered when assessing the ability of this cytokine to complement cytoreductive therapies. PMID- 2196118 TI - Expression of hepatocyte and oval cell antigens in hepatocellular carcinomas produced by oncogene-transfected liver epithelial cells. AB - We have established an in vivo/in vitro system in which epithelial cells ("oval cells") isolated from livers of rats fed a carcinogenic diet for a very brief period are placed in culture and transfected with an oncogene. Injection s.c. into nude mice of oval cells transfected with the activated c-Ha-ras (EJ oncogene) produces tumors with morphological features of differentiated hepatocellular carcinomas. Using monoclonal antibodies that can recognize hepatocyte, oval cell, and tumor antigens, we investigated the expression of these antigens in oval cells in culture, transfected with either the EJ oncogene or the normal c-Ha-ras allele and in tumors derived from the oncogene-transfected cells. We show that EJ-transfected cells and most particularly the tumors they produce expressed hepatocyte and oval cell antigens not detectable in untransfected cells or cells transfected with the normal c-Ha-ras gene. Furthermore, we found that in cloned tumor cells, the expression of hepatocyte antigens could be induced by changes in culture conditions and was accompanied by a decrease in the expression of oval cell markers. Trabecular hepatocellular carcinomas had higher reactivity toward monoclonal antibodies recognizing hepatocyte antigens while tumors with glandular architecture reacted predominantly with monoclonal antibodies against oval cells. We conclude that, in addition to its tumorigenic effect, the EJ oncogene induced the differentiation of tumor cells toward the hepatocyte lineage. In addition, the data provide further confirmation that oval cells can serve as progenitors of differentiated hepatocellular carcinomas. PMID- 2196117 TI - Analysis of human tumor associated Thomsen-Friedenreich antigen. AB - The Thomsen-Friedenrich (TF) antigen is a precursor structure of MN blood group antigens and is also expressed by about 90% of human carcinomas. The immunodominant group of TF antigen [beta-galactosyl(1-3)-alpha-N acetylglactosamine] is present in cryptic form in normal RBC and is revealed by neuraminidase treatment. A murine monoclonal antibody (Mab 49H.8) developed against neuraminidase treated human RBC was reactive against a variety of human tumors. We have characterized the human tumor associated TF antigen detected by this antibody from a human transitional bladder carcinoma cell line (647V), a human colon adenocarcinoma cell line (LS174T), and a pleural effusion fluid of a breast adenocarcinoma patient (PE 89). A heterologous sandwich radioimmunoassay for TF antigen was developed using Mab 49H.8 as the catcher and 125I-peanut agglutinin as the probe. Detergent extracts of 647V and LS174T cells, media conditioned by culturing these cells, and PE 89 were shown to contain the antigen by this assay. The specificity of the antigen capture by Mab 49H.8 in this assay was demonstrated by its selective inhibition by nitrophenyl-beta-D-galactoside, phenyl-beta-D-galactoside, and a TF hapten. Preliminary studies on TF antigen in serum samples using this assay showed that about 53.7% of the carcinoma samples contained an antigen concentration greater than 200 units/ml whereas for 90.9% of the normal samples the antigen concentration was below 200 units/ml. These studies demonstrated that the TF antigen is shed by the tumor cells both in vitro and in vivo. The TF antigen was sensitive to treatment with alkali (0.1 M NaOH for 5 h at 37 degrees C) and periodate (10 mM sodium periodate for 1 h at room temperature), was resistant to acidic pH (50 mM acetate buffer, pH 4.5, for 5 h at 37 degrees C), and could be extracted with perchloric acid (0.6 M for 1 h at 4 degrees C). The antigen was shown to be a high molecular weight glycoprotein (Mr greater than 1,000,000) by gel filtration chromatography. The density of the antigen was estimated to be about 1.35 g/ml by cesium chloride density gradient centrifugation. The antigen could be isolated from conditioned media by a combination of affinity chromatography and gel filtration with an overall purification of about 61,432-fold and a final recovery of 53.2%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2196120 TI - The treatment of sepsis and other complications in the trauma patient. AB - Immediate complications of trauma and shock include right heart failure, acute respiratory distress syndrome, coagulopathy, brain edema, small bowel dysfunction, renal failure, and immune dysfunction. Nosocomial infections are also common in trauma patients. These infections are the combined result of a compromised host defense and various iatrogenic risk factors, including the use of percutaneous drainage tubes, malnutrition, the injudicious use of prophylactic antibiotics, and treatment staff hygiene. The use of prophylactic antibiotics appears to be unwarranted in head, maxillofacial, and neck injuries and is debatable in chest and soft-tissue wounds, fractures, and injuries of the peritoneal cavity. The use of antibiotics in small bowel and colon injuries is justified. Antibiotics are necessary in crush or avulsive injuries. Combination antibiotic therapy often results in multiple complications that may compound the patient's problems. Therefore, a single antibiotic with minimal side effects is the therapy of choice in the surgical intensive care unit. PMID- 2196119 TI - Activation of K-ras by codon 13 mutations in C57BL/6 X C3H F1 mouse tumors induced by exposure to 1,3-butadiene. AB - 1,3-Butadiene has been detected in urban air, gasoline vapors, and cigarette smoke. It has been estimated that 65,000 workers are exposed to this chemical in occupational settings in the United States. Lymphomas, lung, and liver tumors were induced in female and male C57BL/6 X C3H F1 (hereafter called B6C3F1) mice by inhalation of 6.25 to 625 ppm 1,3-butadiene for 1 to 2 years. The objective of this study was to examine these tumors for the presence of activated protooncogenes by the NIH 3T3 transfection and nude mouse tumorigenicity assays. Transfection of DNA isolated from 7 of 9 lung tumors and 7 of 12 liver tumors induced morphological transformation of NIH 3T3 cells. Southern blot analysis indicated that the transformation induced by 6 lung and 3 liver tumor DNA samples was due to transfer of a K-ras oncogene. Four of the 7 liver tumors that were positive upon transfection contained an activated H-ras gene. The identity of the transforming gene in one of the lung tumors has not been determined but was not a member of the ras family or a met or raf gene. Eleven 1,3-butadiene-induced lymphomas were examined for transforming genes using the nude mouse tumorigenicity assay. Activated K-ras genes were detected in 2 of the 11 lymphomas assayed. DNA sequencing of polymerase chain reaction-amplified ras gene exons revealed that 9 of 11 of the activating K-ras mutations were G to C transversions in codon 13. One liver tumor contained an activated K-ras gene with mutations in both codons 60 and 61. The activating mutation in one of the K-ras genes from a lymphoma was not identified but DNA sequence analysis of amplified regions in proximity to codons 12, 13, and 61 demonstrated that the mutation was not located in or near these codons. Activation of K-ras genes by codon 13 mutations has not been found in any lung or liver tumors or lymphomas from untreated B6C3F1 mice. Thus, the K-ras activation found in 1,3-butadiene-induced B6C3F1 mouse tumors probably occurred as a result of genotoxic effects of this chemical. The oncogenes most frequently detected in human pulmonary adenocarcinomas are K-ras genes. Activated K-ras genes have also been found in some human lymphomas. This suggest that activation of K-ras may be important in the induction of human pulmonary adenocarcinomas and lymphomas.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2196122 TI - Intra-abdominal sepsis: a medical-surgical dilemma. AB - Much progress has been made in our understanding of the pathophysiology of intra abdominal infection over the past 100 years. By 1900, investigators had evidence of both an aerobic and an anaerobic component in these infections. By the 1970s, the role of gram-negative aerobic organisms in peritonitis and the role of anaerobes in abscess formation were emerging. Improved culture techniques have demonstrated the true polymicrobial nature of intra-abdominal infection. In our most recent study, an average of 3.9 isolates per patient was cultured. Because of the mixed flora present in these infections, antibiotic regimens must be active against both aerobes and anaerobes. This coverage has usually been accomplished with combinations of antibiotics, although some newer, single-agent regimens may also be effective. Even with our increased knowledge, intra abdominal infection followed by sepsis remains the most common cause of death among patients in the intensive care unit. Mortality is associated with multiple, recurrent, or persisting abscess; positive blood cultures; and organ failure. Surgery, if indicated, should be undertaken before the onset of significant organ failure. Reducing the mortality from organ failure will depend more on the ability to modulate the metabolic and immune pathways that lead to sepsis than on the development of broader-spectrum antibiotics and more aggressive surgical algorithms. PMID- 2196121 TI - Antimicrobial management of postoperative infections in abdominal surgery: single or combination regimen? AB - In a prospective, controlled, randomized study, the clinical and bacteriologic efficacy of imipenem/cilastatin was compared with that of a standard combination of an aminoglycoside, amoxicillin, and clindamycin in patients with serious postoperative infections. Doses used were imipenem/cilastatin 1 gm q 8 hr, amoxicillin 2 gm q 8 hr, and clindamycin 0.6 gm q 6 hr. Aminoglycoside doses were individualized and monitored six times weekly with serum concentration assays. Sixty-three patients were entered into the study: 31 in the imipenem/cilastatin group and 32 in the combination group. Diagnoses included pneumonia (ten in the imipenem/cilastatin group and seven in the combination group), peritonitis (eight in the imipenem/cilastatin group and 15 in the combination group), and septicemia (eight in the imipenem/cilastatin group and three in the combination group). The two groups were comparable with respect to sex, age, underlying diseases, and duration of antibiotic therapy. In the imipenem/cilastatin group, 26 patients were cured and one improved (87%). In the combination group, 21 were cured and five improved (81%). Four patients receiving imipenem/cilastatin and six receiving the combination therapy failed to respond to treatment. Eighty percent of the bacterial isolates were eradicated, and 15% were suppressed in the imipenem/cilastatin group. Corresponding frequencies in the combination group were 84% and 11%, respectively. Isolated pathogens persisted in 5% of the patients in each group. It is concluded that imipenem/cilastatin appears to be an effective and well-tolerated alternative to a triple antibiotic combination in the treatment of serious postoperative infections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196123 TI - Incidence and significance of intraperitoneal aerobic and anaerobic bacteria. AB - Intra-abdominal infections frequently occur after trauma, surgical resections, or intrinsic diseases of the gastrointestinal tract. These infections, which can be generalized or localized in intraperitoneal or extraperitoneal locations as well as in organs, are often difficult to diagnose and treat. They are usually polymicrobial, involving both aerobic and anaerobic bacteria. The average number of bacterial strains recovered is between two and five, with anaerobes dominating. The aerobic microorganisms most commonly recovered are Enterobacteriaceae (mainly Escherichia coli) and enterococci (mainly Enterococcus faecalis). Among the anaerobic microorganisms, Bacteroides fragilis, anaerobic cocci, and clostridia are usually isolated. Adequate surgical drainage and antimicrobial therapy improve the clinical course of intra-abdominal infections and reduce the risk of local complications and septicemia. The choice of antimicrobial agents should be based on the type of infection, the microorganisms most likely to be encountered, and the microbial sensitivity pattern of the clinic. The side-effect profile of the antimicrobial therapy should also be taken into consideration. PMID- 2196124 TI - [Bertina's Spa in Trebon]. PMID- 2196125 TI - HLA-DR expression on human peritoneal macrophages in vivo and in vitro. AB - Qualitative, semi-quantitative (immuno-electronmicroscopy), and quantitative (radioimmunoassay) measurements were made of the in vivo and in vitro expression of HLA-DR on continuous ambulatory peritoneal dialysis (CAPD) patients' peritoneal macrophages (M phi) and on healthy persons' blood monocytes (MO). In vivo, great variation is seen in both the qualitative and (semi-) quantitative expression of HLA-DR in peritoneal M phi. After culturing for 5 to 20 h, CAPD patients' M phi with low to intermediate numbers of HLA-DR molecules per cell (25 80 x 10(3] showed a two- to threefold enhancement of HLA-DR expression. This enhancement was determined for the total peritoneal cell (PC) population and for the adherent subpopulation of peritoneal M phi and blood MO. CAPD patients whose cells initially had high numbers of HLA-DR molecules (80-110 x 10(3] showed no or only slight enhancement of HLA-DR expression when cultured. PMID- 2196126 TI - Increased activity of digoxin-like substance in low-renin hypertension in acromegaly. AB - Arterial hypertension is common in acromegaly, but the pathogenesis of this complication remains unknown. To determine the role of an endogenous Na,K pump inhibitor/digoxin-like substance (DLS) in the pathogenesis of hypertension in acromegaly 76 subjects: 28 with acromegaly, 20 with essential hypertension and 28 healthy controls were studied. Serum DLS was measured with the use of radioimmunoassay and bioassay by the inhibition of digoxin-sensitive erythrocyte 86-Rb uptake. In acromegaly, the activity of DLS was significantly increased and plasma renin activity decreased in the hypertensive group, as compared with that of the normotensive group and controls. Moreover, DLS was elevated in the low renin group of essential hypertension, as compared with that of the normal/high renin group or controls. The activity of DLS correlated positively with mean arterial pressure and negatively with plasma renin activity, but not with growth hormone levels. IN CONCLUSION: an endogenous sodium pump inhibitor/digoxin-like substance may play a role in the pathogenesis of low-renin hypertension in acromegaly. PMID- 2196127 TI - Inhibitory effects of kinins on angiotensin I conversion in the local circulation. AB - The inhibition of angiotensin converting enzyme (ACE) by kinins was studied using bradykinin (BK), lysyl-bradykinin (Lys-BK), [Hydroxyproline3]-bradykinin ([Hyp3] BK) and [Hydroxyproline3]-lysyl-bradykinin ([Hyp3]-Lys-BK). The latter two are novel kinins recently identified in our laboratory. All the four kinins displayed competitive inhibition on the conversion of angiotensin I to angiotensin II by purified canine lung ACE. Inhibition constants (Ki) for the four kinins were estimated from Dixon's plot as follows-BK: 0.27 microM, Lys-BK: 0.57 microM, [Hyp3]-BK: 0.34 microM, and [Hyp3]-Lys-BK: 0.27 microM. In the rat hindlimb perfusion system, the kinins were demonstrated to partially inhibit angiotensin I conversion to angiotensin II by the vascular ACE. Taken together, these results suggest that angiotensin II formation by ACE in the vascular tissue is possibly inhibited by local kinins, especially after ACE inhibitor administration. This indirect action of kinins, coupled with its direct vasodilatory action, might indicate a cooperative participation in vasodilation. PMID- 2196128 TI - Pheochromocytoma in children: difficulties in diagnosis and localization. AB - Surgically confirmed pheochromocytoma was the cause of arterial hypertension in 6 out of 668 (0.8%) children with significant hypertension admitted to Child Health Centre in Warsaw. Among clinical features most characteristic was sustained hypertension observed in all patients, often complicated by the accelerated phase of malignant hypertension and encephalopathy. Sustained tachycardia was also found in all patients. Elevated sedimentation rate and electrocardiographic changes were observed in each child while other abnormal laboratory findings such as hyperglycemia, etc. occurred at similar rate as in adults. Increased urinary excretion of catecholamines and their metabolites confirmed the diagnosis. In our study the most sensitive methods for tumor localization were ultrasonography and computed tomography of the adrenals while scintigraphy with iodo-131 metabenzylguanidine gave a high percentage of false negative results. Clinical presentation of pheochromocytomas in children is different than in adults and all pediatric patients with severe hypertension should be screened for this disease. PMID- 2196130 TI - Pharmacologic approaches to the prevention and treatment of neonatal hyperbilirubinemia. AB - Because of the high frequency, serious sequelae, and complex and costly management, neonatal jaundice is a good candidate for preventive treatment. In this respect the clinical problem of neonatal jaundice has many similarities with the problem of hemorrhagic disease of the newborn. Both conditions are transient peculiarities of newborn metabolism. Most neonates exhibit the biochemical abnormality, but a small minority is placed in jeopardy of life or suffers serious sequelae. In both conditions a loose relationship exists between the degree of biochemical abnormality and the clinical manifestations that are poorly predicted by monitoring the abnormalities. The administration of vitamin K at birth corrected the biochemical abnormalities and eliminated clinical hemorrhagic disease. The simplicity, efficacy, and safety of vitamin K prevention of hemorrhagic disease of the newborn is the prototype in the search for the solution to the problem of neonatal jaundice. For most neonates, antenatal phenobarbital comes close to this prototype in terms of efficacy and simplicity. The combination of antenatal and postnatal therapy seems suitable for use in preterm labor in combination with tocolysis. This recommendation is conditional on the demonstration of safety by long-term follow-up. The competitive inhibition of HO by synthetic metalloporphyrins offers an even simpler solution, but the level of efficacy achieved with the doses and compounds used so far are not comparable with that of phenobarbital. For the time being, phenobarbital is recommended for population groups with high risk of severe neonatal jaundice, or scarcity of resources for the management of neonatal jaundice with phototherapy and exchange transfusion. PMID- 2196129 TI - Further studies on the noradrenergic and the renin-angiotensin systems in the brain of the rat. AB - Previous investigations have shown that depletion of brain norepinephrine (NE) induced by chemical sympathectomy resulted in significant changes in the central renin-angiotensin system. The purpose of the present work was to increase the NE concentration in the central nervous system (CNS) in order to analyze its effect on the peptidergic complex and on the blood pressure (BP) levels. Treated rats were given the following drugs in the drinking water: 1-dopa (12 mg/rat/day), carbidopa (6 mg/rat/day) and pargyline (10 mg/rat/day) during 25 days. BP was determined, blood and cerebrospinal fluid (CSF) samples were obtained. The CNS was dissected into several areas. NE, angiotensinogen (AoC) and renin concentration (RC) were determined in the brain parenchyma; AoC was evaluated in CSF and plasma samples. Pharmacological treatment resulted in an hypotensive effect and, at the same time, an increase of NE in the CNS (about 100%; p less than 0.0005). These changes were accompanied by a significant decrease in the peripheral and central AoC. These results add new evidence to the postulated relationship between these two important regulatory systems involved in cardiovascular control. PMID- 2196131 TI - Developmental biology of heme oxygenase. AB - The regulation of heme oxygenase activity in the developing neonate is essential to the control of bilirubin production as well as intracellular heme and hemoprotein metabolism. The coordinated activity of the microsomal enzymes, heme oxygenase and NADPH-cytochrome c (P450) reductase, and the cytosolic enzyme biliverdin reductase is responsible for the degradation of heme. The complete reaction sequence requires oxygen and NADPH, and produces bilirubin and carbon monoxide in equimolar amounts. Although heme oxygenase expresses a rather broad range of substrate affinities, the oxidative degradation of heme is exclusively alpha-specific. Heme oxygenase is found in several tissues, with significant activity levels in the liver, spleen, and erythropoeitic tissue. Heme oxygenase activity is inducible by heme and other metalloporphyrins, hormones, starvation, stress, toxins, and xenobiotics. Heme oxygenase induction is generally considered to be the result of an increased protein synthesis and gene transcription. This hypothesis is supported by recent studies of the heme oxygenase gene that identified inducer element binding sites responsive to metal administration, heat shock, and nutrient availability. In the developing fetus and neonate, hepatic heme oxygenase activity and mRNA levels are elevated above that of the adult. This suggests that the elevated heme catabolism observed in neonates may be associated with an increased transcription of the heme oxygenase gene. The apparent induction of hepatic heme oxygenase during the neonatal period is probably the result of tissue-specific and time-dependent transcriptional regulating factors including potentially hormones and heme. Several metalloporphyrins, such as the tin and zinc porphyrin complexes, inhibit heme oxygenase activity and thus have therapeutic potential for the treatment of neonatal jaundice. Recent studies suggest that the meso- and bis-glycol derivatives of these metalloporphyrins may be more potent inhibitors of heme oxygenase activity in vitro and in vivo than the protoporphyrin structures. As structural analogues of heme, however, these compounds may also have other less desirable effects on the regulation of heme and hemoprotein metabolism, particularly in the developing neonate. PMID- 2196132 TI - New approaches to assessing the risks of hyperbilirubinemia. AB - The issue of what is a critical threshold of bilirubin for the neonate in terms of long-term morbidity, however, remains unanswered. The recent large prospective study carried out in the Netherlands by Van de Bor et al. to evaluate the effect of bilirubin on 2-year neurodevelopmental outcome of premature infants with a birthweight less than 1500 gm identified a consistent increase in handicap rate for each 2.9 mg/dl (50 microns mol/L) increase in maximum bilirubin concentration. The percentage of children with both minor and major handicaps increased consistently with increased bilirubin concentration. Logistic regression analysis with the maximum serum bilirubin concentration as the continuous variable and controlling for seven other risk factors identified an odds ratio for handicap of 1.3 with a 95% confidence interval between 1.03 and 1.62, (P less than 0.02). These data suggest that a relationship exists between mild and moderate levels of bilirubin and neurodevelopmental handicap at 2 years of age in premature infants. Van de Bor's study is important because it suggests that we must continue to investigate the risk of low to moderate levels of bilirubin in both premature and full-term infants. The study of neonatal alterations of behavior, BAER conduction time, and cry characteristics in infants with hyperbilirubinemia lends support to the hypothesis that low levels of bilirubin result in neonatal neurobehavioral changes that can be easily measured and recorded by these techniques. BAER changes are mediated by the eighth cranial nerve pathway, and cry characteristics are mediated by the vagal complex cranial nerves. The nuclei of these cranial nerves are located in close proximity to one another in the brainstem, and therefore the insult imposed by bilirubin is reflected not only in changes of these two parameters but by behavioral manifestations (i.e., specifically orientation). Finally, however, evidence exists that reversals of these measured changes do occur after treatment modalities such as exchange transfusion or phototherapy are used. The question of a safe level of bilirubin concentration, and safe duration of exposure relative to long-term minor or soft neurodevelopmental handicaps remains unanswered. Large, controlled, prospective, epidemiologic studies are needed to provide these answers. PMID- 2196133 TI - Does hyperbilirubinemia damage the brain of healthy full-term infants? AB - In the 1950s, exchange transfusion to keep the total serum bilirubin below 20 mg/dl was shown to be an effective way of preventing kernicterus in babies with erythroblastosis fetalis. For the last 15 to 20 years this level has also been used to determine the need for intervention in healthy full-term infants who do not have hemolytic disease. A critical review of all the available data including six studies from the collaborative perinatal project (more than 30,000 infants) and several smaller studies of term infants without hemolysis reveals essentially no evidence of adverse effects of bilirubin on IQ, neurologic examination, or hearing. The investigation and treatment of normal infants with jaundice is expensive and potentially harmful. We need to reassess our approach to hyperbilirubinemia in healthy full-term infants. PMID- 2196134 TI - Is bilirubin good for you? AB - Bilirubin is generally considered to be a diagnostically useful, sometimes toxic, metabolic waste product--and nothing more. Many studies, however, summarized in this article, have shown that bilirubin is an effective lipid-soluble antioxidant in vitro, even at physiologic concentrations, vying with even vitamin E in its ability to intercept and inhibit free radical chain reactions that generate hazardous lipid peroxides. These studies suggest that bilirubin may have a biochemical function in vivo and belong to a group of low-molecular weight antioxidants that together provide protection from cellular damage by endogenous organic free radicals. Dovetailing with the notion that bilirubin may have a protective function is the recent discovery that heme oxygenase, one of the enzymes responsible for bilirubin formation, is a heat-shock protein, one of a group of proteins that are thought to protect organisms from oxidative and other forms of biochemical stress. Thus, the biochemical path from red to green to yellow may defend as well as degrade, and modest levels of the end product may possibly be physiologically beneficial. PMID- 2196135 TI - Clinical features of bilirubin encephalopathy. AB - Clinical features of bilirubin encephalopathy vary depending on the age of the infant and the degree of hyperbilirubinemia. In term infants with hyperbilirubinemia, three distinct clinical phases are apparent in the first weeks of life, and long-term consequences include extrapyramidal disturbances (particularly athetosis), hearing loss, gaze abnormalities (particularly limitation of upward gaze), and, in a minority, intellectual deficits. In term infants with moderate hyperbilirubinemia, minor delay in motor development during the first year has been demonstrated, but with longer follow-up this delay is not apparent. Associated conditions such as sepsis, anoxia, and acidosis may increase the likelihood of neurotoxicity of bilirubin in these infants. The clinical consequences of moderate hyperbilirubinemia in premature infants are unclear. No acute clinical syndrome is recognizable during the first weeks. The results of follow-up studies are variable. Hearing loss is the commonest consequence. Follow up through age 2 years in one large study suggests that static encephalopathy may be a sequel. Longer follow-up is needed to understand the clinical consequences of moderate hyperbilirubinemia in this important group of infants. PMID- 2196136 TI - Autopsy findings associated with neonatal hyperbilirubinemia. AB - Hyperbilirubinemia is associated with bilirubin deposition in tissue in the newborn including the liver, kidney, heart, adrenal, lung, and brain. High levels of serum bilirubin will stain the skin and sclera and be called "jaundice" clinically, and similarly high levels of bilirubin will stain tissues internally, preferentially in areas of tissue damage. Whether the bilirubin causes the damage or marks the damage because of other insults or both remains controversial. PMID- 2196137 TI - Laboratory measurement of bilirubin. AB - Several methods for determination of total bilirubin and its fractions have been critically discussed. Methods for serum determinations are summarized in Table 1. Because results of direct bilirubin cannot necessarily be equated with conjugated bilirubin, care must be taken in interpreting results from different laboratories, and clinicians are encouraged to become familiar with methods in use at their own institutions. Despite problems reported in the literature, bilirubin determinations, together with a reference range established for one's own patient population, should provide valuable information for patient management. PMID- 2196138 TI - Noninvasive measurements of bilirubin in the newborn. AB - Technologic advances have allowed a means for more precise measurement of cutaneous bilirubin. These advances have led investigators to examine the correlation between cutaneous and blood bilirubin in hopes of either replacing or reducing the number of serum bilirubin values obtained. In the past other investigators attempted to do the same, using visual estimates of jaundice with and without the help of reference devices. The establishment of an acceptable correlation between cutaneous and serum bilirubin requires (1) accurate measurement of serum bilirubin, (2) accurate measurement of cutaneous bilirubin, and (3) steady-state conditions between the blood-cutaneous bilirubin "compartments." The accuracy with which cutaneous bilirubin can be measured appears similar or better than that with which serum bilirubin is measured; with older transcutaneous devices significant interobserver variability may exist. Bias in the form of other skin chromogens also interferes with accuracy. Rapid changes in serum or cutaneous bilirubin concentration or nonhomogeneous distribution of cutaneous bilirubin interferes with our knowledge of cutaneous blood bilirubin kinetics. At present transcutaneous bilirubinometry cannot replace routine serum measurements, but both new and old transcutaneous devices can serve as effective screening devices. The choice of which device to use depends on its cost-effectiveness in any given clinical setting. PMID- 2196139 TI - The neurotoxicity of bilirubin. AB - Recent clinical and research findings on kernicterus and bilirubin toxicity are reviewed. Bilirubin binds to cell membranes and appears to interfere with the metabolism, depolarization, and transmitter functions of neurons. The neurobehavioral and clinical findings associated with bilirubin encephalopathy and low bilirubin kernicterus are presented and evaluated. Cardiorespiratory stabilization, avoidance of displacing drugs, and preventive use of phototherapy appear to have decreased the incidence of low bilirubin kernicterus in high-risk newborns. PMID- 2196140 TI - How bilirubin gets into the brain. AB - The last decades of bilirubin research seem to have clarified the basic mechanisms by which bilirubin enters the brain. Clinical studies have so far failed to show any value of the presently known risk factors in predicting bilirubin toxicity in the newborn infant, however. This indicates that bilirubin entry into the brain does not necessarily equal bilirubin toxicity. Future research must therefore concentrate on further clarifying the molecular basis for the interaction between the nerve cell membrane and bilirubin as well as bilirubin effects on nerve cell metabolism. Such studies may eventually form the basis for a more rational prophylaxis and a more specific therapy than that which is currently being employed. PMID- 2196141 TI - Blue light, green light, white light, more light: treatment of neonatal jaundice. AB - This article reviews the current understanding of how phototherapy, the most widely used treatment of neonatal jaundice, uses light energy to pump bilirubin out of a jaundiced infant. It provides a framework for understanding the often conflicting results of clinical comparisons of various phototherapeutic regimens, and stresses the importance of light intensity in the overall effectiveness of phototherapy. PMID- 2196142 TI - Cholestatic jaundice in the newborn. AB - Neonatal cholestasis or direct hyperbilirubinemia in the first 3 months of life is nearly always more pathologic than physiologic. This article reviews the extensive differential diagnosis of cholestatic jaundice and the approach to diagnosis. A sense of urgency is underscored by the value of early recognition and intervention in metabolic, iatrogenic, and anatomic disorders. The long-term management goals are reviewed, including indications for hepatic transplantation. PMID- 2196143 TI - The effect of olestra on systemic levels of oral contraceptives. AB - The effect of olestra, a nonabsorbable, noncaloric fat replacement, on the absorption and efficacy of a highly lipophilic oral contraceptive was investigated in a double-blind, placebo-controlled crossover study with 28 women. Subjects consumed 18 gm/day olestra for 28 days while taking an oral contraceptive containing 300 micrograms of norgestrel and 30 micrograms ethinyl estradiol (Lo/Ovral-28). Blood taken on days 12 to 14 of the treatment cycles was analyzed for ethinyl estradiol and norgestrel. There was no statistically significant difference in time to attain maximum concentration, maximum concentration, or area under the concentration-time curve between the olestra and placebo treatments for either drug component. Measurements of serum progesterone indicated that olestra ingestion did not reduce efficacy as indicated by ovulation. The data show that ingestion of 18 gm/day olestra did not affect the absorption or efficacy of the highly lipophilic oral contraceptive. PMID- 2196144 TI - Hemodynamic effects of quinapril, a novel angiotensin-converting enzyme inhibitor. AB - The hemodynamic effects of quinapril, a novel nonsulfhydryl-containing angiotensin-converting enzyme (ACE) inhibitor, were assessed in 10 patients with mild-to-moderate essential hypertension. Compared with placebo, quinapril (20 mg) administered twice daily for 4 weeks significantly lowered blood pressure by decreasing total peripheral resistance without producing tachycardia, an increase in cardiac output, or a rise in plasma catecholamines. Quinapril significantly reduced renal, but not forearm, vascular resistance. Renal blood flow, glomerular filtration rate, and filtration fraction remained unchanged. Left ventricular wall stress was markedly reduced by quinapril, but during the relatively short treatment period, only a nonsignificant trend toward reduction in left ventricular mass was observed. These findings suggest that quinapril is an effective antihypertensive agent that lowers peripheral resistance without increasing cardiac output or disturbing autoregulation of renal hemodynamics. PMID- 2196145 TI - Dose-response effects of pentoxifylline on erythrocyte filterability: clinical and animal model studies. AB - Ten patients with chronic occlusive arteriosclerosis received single oral doses of 100, 200, 400, 800, and 1200 mg pentoxifylline in a single-blind, placebo controlled study. Blood samples were drawn at baseline and at 2 hour intervals for 6 hours. Drug and metabolite levels, as well as red cell filterability (deformability), were determined on all blood samples. Statistically significant dose-response increases of red cell filterability were found 4 and 6 hours after oral medication with the dosages of 200 to 1200 mg pentoxifylline. These changes were proportional to the plasma levels of pentoxifylline and metabolites 1 and 5 of this agent. Attempts were made to develop a suitable animal-screening method for agents with similar activity and to determine whether red blood cells in the absence of disease-related abnormalities may respond to this type of therapy. Five healthy Macaca arctoides monkeys were given 24 mg/kg pentoxifylline intravenously, and measurable but lesser increases in red cell deformability were recorded than in the patients. PMID- 2196146 TI - Stimulant drug treatment of hyperactivity: biochemical correlates. AB - To compare the effects of the stimulant drugs dextroamphetamine and methylphenidate on urinary and plasma monoamines and metabolites within the same clinical sample, thirty-one children with attention-deficit disorder with hyperactivity were treated with dextroamphetamine (up to 1.5 mg/kg/day), methylphenidate (up to 3.0 mg/kg/day), and placebo in an 11-week double-blind crossover trial. As expected, both drugs showed striking clinical efficacy, and within a subsample of the group, earlier findings were confirmed, that dextroamphetamine but not methylphenidate lowered urinary and plasma 3-methoxy-4 hydroxyphenylglycol and whole body norepinephrine turnover, and that urinary and plasma concentration of homovanillic acid was unaltered by either drug. Methylphenidate but not dextroamphetamine increased plasma norepinephrine. Urinary epinephrine and metanephrine were increased with both drugs, but this increase did not correlate significantly with clinical improvement. PMID- 2196147 TI - Intrapatient comparison of acute hemodynamic, hormonal, and natriuretic responses to captopril versus enalapril in liver cirrhosis. AB - We compared acute hemodynamic, hormonal, and natriuretic responses to a single oral dose of captopril (50 mg) versus enalapril maleate (10 mg) administered to eight patients with biopsy-proved liver cirrhosis. Although the two angiotensin converting enzyme (ACE) inhibitors lowered (p less than 0.05) blood pressure with no change in heart rate during the early postdose period, captopril produced a greater (p less than 0.05) hypotensive effect than did enalapril. Enalapril caused a greater (p less than 0.01 to 0.05) ACE inhibition than did captopril during the 2- to 48-hour postdose period. Plasma renin activity increased (p less than 0.05) with the two drugs and returned toward baseline by 12 hours after administration. Plasma aldosterone levels, elevated before drug administration, were decreased by the two drugs in a stepwise fashion, but the suppressive effect was greater (p less than 0.01 or p less than 0.05) after captopril than after enalapril. Natriuresis was greater (p less than 0.05) during the first 24-hour period after enalapril than after captopril. The findings indicate that the acute pharmacodynamic responses to the two ACE inhibitors differ in patients with liver cirrhosis. However, the mechanism(s) of the divergent effects of the two drugs and the clinical implications remain obscure from this single-dose study. PMID- 2196148 TI - Extravascular penetration of ciprofloxacin. A review. AB - The pharmacokinetics of ciprofloxacin after oral and intravenous administration have been studied extensively, and the results have been published worldwide. This paper serves as a review of the pharmacokinetics of ciprofloxacin, with specific reference to its penetration into body fluids and tissues. Ciprofloxacin has a protein binding of approximately 30% and penetrates well into tissues. For instance, the total concentration (area under the serum concentration-time curve) in peripheral human lymph is 70% of the serum values, and the peak level in lymph appears with 1-2 hr. The corresponding value for suction skin blisters is 60% and for inflammatory blisters 120%. Ciprofloxacin is concentrated in white blood cells, lung, prostate, and kidney and reaches concentrations above serum in many other tissues as well. Urine concentrations are up to 100 times those in serum. The levels in bile are comparable or only slightly higher (less than or equal to x 10) than serum levels. The penetration into cerebrospinal fluid (CSF) is low; the CSF levels are 4-10% of the serum levels in noninflammatory CSF and 30-50% in CSF from patients with meningitis. PMID- 2196149 TI - Prospective randomized study comparing the efficacy and safety of ciprofloxacin with cefaclor in the treatment of patients with purulent bronchitis. AB - We compared safety and efficacy of ciprofloxacin and cefaclor in the treatment of patients with purulent bronchitis. Fifty-five patients were randomized prospectively to receive ciprofloxacin with a dose of 500 mg orally twice daily or cefaclor 250 mg over 8 hr for 5 days or longer. Patient groups did not differ with respect to age, duration of illness, severity of infection, or number of other concomitant disease states. A significantly larger number of patients in the ciprofloxacin group had poor health status (39.3% vs 7.4% for the ciprofloxacin and cefaclor groups, respectively, p = 0.02). The response to therapy did not differ between groups. Infection was completely resolved in 71.4% vs 66.7% and markedly improved in 7.1% and 11.1% for the ciprofloxacin and cefaclor groups, respectively. The response to therapy and adverse reaction rate did not differ between groups. Seven patients treated with ciprofloxacin and five patients treated with cefaclor developed adverse reactions. We conclude that ciprofloxacin is a useful agent for the treatment of purulent bronchitis. PMID- 2196150 TI - A prospective, double-blind, randomized study comparing the efficacy and safety of low-dose ciprofloxacin with ampicillin in the treatment of bronchitis. PMID- 2196151 TI - Parenteral ciprofloxacin compared with ceftazidime in the treatment of serious upper and lower urinary tract infection. PMID- 2196152 TI - Intravenous and oral ciprofloxacin versus intravenous ceftazidime for the treatment of severe urinary tract infections. PMID- 2196153 TI - Comparison of intravenous ciprofloxacin with ceftazidime in the treatment of serious soft tissue infections. PMID- 2196154 TI - Ciprofloxacin in the treatment of Staphylococcus aureus osteomyelitis. A review. PMID- 2196155 TI - Ciprofloxacin as single-dose antibiotic prophylaxis in colorectal surgery. Results of a randomized, double-blind trial. PMID- 2196156 TI - Safety of intravenous ciprofloxacin in healthy volunteers after multiple dosing. A review. PMID- 2196157 TI - Luteal oxytocin: characteristics and control of synchronous episodes of oxytocin and PGF2 alpha secretion at luteolysis in ruminants. PMID- 2196160 TI - Gonadotropin-releasing hormone inhibition of LH stimulated progesterone secretion by porcine granulosa cells in vitro. AB - GnRH has several direct actions on rat granulosa cells. Specific receptors for GnRH have been demonstrated on rat and human ovaries. Whether the porcine ovary has specific receptors for GnRH is still debated and the physiological actions of GnRH on porcine granulosa cells have not yet been clarified. Consequently, we have examined the actions of a GnRH agonist (GnRHa) on basal and LH stimulated progesterone secretion by porcine granulosa cells. GnRHa inhibited both basal and LH stimulated progesterone secretion by granulosa cells from medium (3-5 mm) and large (6-10 mm) antral follicles during 3 day incubations. LH stimulated progesterone secretion was more sensitive to inhibition than basal progesterone secretion. Studies on the time course for GnRHa inhibition of progesterone secretion indicated that the decrease in progesterone secretion occurred 48 to 72 hr after first exposure to GnRHa. Earlier inhibition occurred in only a fraction of the experiments. GnRHa did not have to be present during the time when inhibition occurred. Incubations of 2 days with GnRHa were just as effective as 3 day incubations at inhibiting progesterone secretion on day 3. Furthermore, a 30 min exposure to GnRHa on day 1 was just as inhibitory as a full 2 day incubation with GnRHa in inhibiting LH stimulated progesterone secretion on day 3. Incubation of the cells for 3 days prior to exposure of the cells to GnRHa did not alter the time course for GnRHa action. GnRHa did not alter the DNA content of the cultures in up to 6 day incubations or the number of viable cells attached to the wells in up to 3 day incubations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196159 TI - Effects of ractopamine on adipose tissue metabolism and insulin binding in finishing hogs. Interaction with genotype and slaughter weight. AB - Twenty-four barrows were divided among eight treatments in a 2 x 2 x 2 design to quantify the influence of ractopamine (0 or 20 mg/kg diet) over the final 40 kg of gain on metabolic activity in adipose tissue. Interactions with genotype (Hampshire cross or Landrace cross) and slaughter weight (100 or 127 kg) were investigated also. Backfat was removed at slaughter and rates of lipolysis and fatty acid synthesis (FS), activities of malic enzyme (ME) and fatty acid synthetase (FAS), and insulin binding to adipocytes were assessed. Adipocytes from ractopamine-fed pigs were less sensitive (EC50 increased 90%) and had a lower maximum lipolytic response (40%) to ractopamine stimulation. Rates of basal and insulin-stimulated FS were decreased 40% in ractopamine-fed pigs and were reflected in lower activities of ME (50%) and FAS (15%). Breed and slaughter weight had no consistent influence on the ractopamine response. Landrace-cross pigs had greater insulin binding capacity (30-60%) whether data were expressed on a cell or surface area basis. Ractopamine feeding did not consistently affect insulin binding capacity. Results suggest that ractopamine interacts in vivo with the beta-adrenergic receptor of swine adipocytes, decreasing lipogenic capacity and diminishing responsiveness to beta-adrenergic stimulation. PMID- 2196161 TI - Sequence signals in eukaryotic upstream regions. AB - Two DNA sequence elements are known to recur frequently upstream of eukaryotic polymerase II-transcribed genes. The TATAAA, at position -40, specifies the transcription initiation site. The GGCCAATCT is less frequent around -80. Sequence analysis of upstream regions reveals that the underlined yeast UAS2 consensus sequence, TGATTGGT, is also very frequent at -80 in higher polymerase II-transcribed animal sequences. The underlined CCAAT box and yeast UAS sequences are complementary. Structural analysis suggests some symmetry in their DNA structures. Upstream of the TATAAT-rich region there is an abundance of GC sequences. Analysis of nucleotide tracts indicates that these are preferentially flanked by their complementary nucleotides with a pyrimidine-purine junction, i.e., TTAN, CCGn, CnGG, TnAA. Here, I discuss DNA structural consideration in upstream regions along with protein readout of the major and minor groove information content. These sequence-structure aspects are put in the general context of protein (factors)-DNA (elements) recognition and regulation. PMID- 2196158 TI - Energy balance and body condition influence luteal function in Holstein heifers. AB - A factorial experiment was conducted to determine influence of energy balance (EB) and body condition (BC) on luteal function in heifers. Heifers with moderate (MBC) or fat (FBC) BC were fed individually to sustain positive EB (PEB) or to cause negative EB (NEB). Intake of feed was measured daily and body weight weekly. Progesterone was quantified daily in serum for 3.5 estrous cycles. On days 9, 10, or 11 after fourth estrus, blood was sampled every 15 min for 12 hr to quantify luteinizing hormone (LH), growth hormone (GH), insulin and non esterified fatty acids (NEFA). The next day, luteal cells were incubated and proportions of small to large cells were determined. After fourth estrus, area of progesterone profiles in serum for 10 days postestrus was reduced in all heifers relative to MBC-PEB heifers. But, luteal weight from FBC-PEB and MBC-NEB heifers was less than MBC-PEB heifers and FBC-NEB heifers were intermediate. Secretion of progesterone in vitro was increased by LH for PEB but not NEB heifers. MBC-NEB heifers had increased ratios of small to large luteal cells. Independent of BC, NEB decreased concentrations of insulin and increased GH and NEFA. Secretion of progesterone was not associated with LH, GH or insulin, but was correlated negatively with NEFA. We conclude that reduced concentrations of progesterone in serum of FBC-PEB and MBC-NEB heifers is due to impaired luteal development. But, reduced concentrations of progesterone in serum of NEB heifers is due also to reduced basal (MBC) and LH-induced (MBC and FBC) secretion of progesterone by luteal cells. Body condition at onset of NEB may determine when effects of NEB on progesterone are detected. PMID- 2196162 TI - Inhibition of bacterial attachment: examples from the urinary and respiratory tracts. PMID- 2196163 TI - Is salt restriction relevant and feasible as adjunctive treatment of hypertension? PMID- 2196165 TI - Rational treatment of acid-base disorders. AB - Acid-base derangements are encountered frequently in clinical practice and many have life-threatening implications. Treatment is dependent on correctly identifying the acid-base disorder and, whenever possible, repairing the underlying causal process. Bicarbonate is the agent of choice for the treatment of acute metabolic acidosis. Controversy surrounds the use of alkali therapy in lactic acidosis and diabetic ketoacidosis, but bicarbonate should clearly be administered for severe acidosis. In most patients with mild to moderate chloride responsive metabolic alkalosis, providing an adequate amount of a chloride salt will restore acid-base balance to normal over a matter of days. In contrast, therapy of the chloride-resistant metabolic alkalosis is best directed at the underlying disease. When alkalemia is severe, administering hydrochloric acid or a hydrochloric acid precursor may be necessary. Treatment of respiratory acidosis should be targeted at restoring ventilation; alkali should be administered only for superimposed metabolic acidosis. The therapy of respiratory alkalosis is centred on reversal of the root cause; short of this goal, there is no effective treatment of primary hypocapnia. The coexistence of more than one acid-base disorder (i.e. a mixed disorder) is not uncommon. When plasma bicarbonate concentration and arterial carbon dioxide tension (paCO2) are altered in opposite directions, extreme shifts in pH may occur. In such cases, it is imperative that the nature of the disturbance is identified early and therapy directed at both disorders. PMID- 2196164 TI - Current therapy of chronic liver disease. AB - The study of chronic liver disease has been hampered by insufficient information relative to the pathogenesis of the many forms of hepatitis. Consequently, well designed treatment strategies are frequently lacking. Wilson's disease is characterised by excessive copper accumulation in the liver and other organs. While d-penicillamine is clearly effective, many patients may not tolerate its many adverse effects. Trientine, oral zinc and unithiol have all shown promise as therapeutic alternatives. Autoimmune chronic active hepatitis responds well to prednisone and azathioprine. Cyclosporin has also produced clinical improvement in several case reports but no comparison has yet been made with the current standard therapy. Recombinant interferon-alpha (IFN alpha) has demonstrated the ability to inhibit hepatitis B viral replication, and the combination of oral corticosteroids followed by IFN alpha is more effective than either agent alone in eliminating viral replication in patients with chronic active hepatitis B. Currently, primary sclerosing cholangitis (PSC) has no standard medical management, but corticosteroids and methotrexate may each have a future role in its treatment. Drug treatment for primary biliary cirrhosis (PBC) has been disappointing, and early reports of success with d-penicillamine were not confirmed in large well-controlled trials. While some reports of improvement with several agents have been described, larger studies are still needed. Alcoholic liver disease continues to be associated with significant morbidity and mortality and numerous investigators have researched several different medical avenues of treatment. Success reported with androgens and the antithyroid agent propylthiouracil in alcoholic liver disease will need confirmation by other research before these agents can be recommended for routine use. Finally, colchicine may prove to be effective in slowing the rate of fibrosis in cirrhosis, but this has yet to be conclusively proven. PMID- 2196166 TI - Therapy of toxic shock syndrome. AB - Toxic shock syndrome (TSS) is an acute febrile, exanthematous illness associated with multisystem failure including shock, renal failure, myocardial failure and adult respiratory distress syndrome (ARDS). It usually presents with fever, pharyngitis, diarrhoea, vomiting, myalgia, and a scarlet fever-like rash, and may progress rapidly (within hours) to signs of hypovolaemic hypotension such as orthostatic dizziness or fainting. The signs and symptoms of toxic shock syndrome should be recognised early to permit successful therapy. Patients are usually suffering from hypovolaemia due to leaky capillaries and fluid loss into the interstitial space, and consequently large volumes of fluid, both crystalloid (e.g. saline, electrolyte-solutions) and colloid (e.g. albumin, intravenous gamma globulin), may be necessary to maintain adequate venous return and cardiac output. Patients with toxic shock syndrome usually have a focus of staphylococcal infection such as a surgical wound infection or soft tissue abscess, or they may have TSS associated with menstruation and use of a vaginal device such as tampons. The site of infection should be adequately drained and treated with antimicrobial therapy. Subacute complications including ARDS and myocardial failure require a thorough understanding of the underlying pathophysiology to ensure appropriate treatment. Recurrences of TSS can be avoided by appropriate antimicrobial treatment and avoidance of recurrent conditions which might favour staphylococcal toxin production (e.g. use of tampons during menstruation). More than 95% of patients survive toxic shock syndrome if appropriate therapy is instituted early. PMID- 2196169 TI - Ketamine, phencyclidine, and MK-801 protect against kainic acid-induced seizure related brain damage. AB - Recent evidence implicates the endogenous excitotoxin, glutamate (Glu), in several neurologic disorders, including seizure-related brain damage. Ketamine, phencyclidine, and MK-801, which are noncompetitive antagonists of the N-methyl-D aspartate (NMDA) subtype of Glu receptor (but do not antagonize kainic acid receptors) were tested in the present study for their effects on behavioral and/or electrographic seizures and seizure-related brain damage induced by kainic acid. Behavioral seizure activity was reduced by these agents, as was spread of electrographic seizures to neocortex, but seizures recorded from deep brain regions such as hippocampus, piriform cortex, and amygdala were not significantly diminished. All three agents prevented seizure-related brain damage in the amygdala, piriform cortex, thalamus, and CA1 region of the hippocampus but conferred little or no protection in the lateral septum and CA3 region of the hippocampus. The regional selectivity of the neuroprotective effect suggests that NMDA receptors may play a more dominant role in seizure-related brain damage in some brain regions than in others. The ability of NMDA antagonists to prevent seizure-related damage in several brain regions without suppressing seizure activity suggests that in these brain regions persistent seizure activity can be maintained by other transmitter systems, with or without NMDA receptor participation, but that seizure-related brain damage is critically dependent on NMDA receptor participation. PMID- 2196167 TI - Fluconazole. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in superficial and systemic mycoses. AB - Fluconazole is a bis-triazole antifungal drug with novel pharmacokinetic properties (metabolic stability, relatively high water solubility) which contribute to its therapeutic activity. Clinical experience is limited to a relatively small number of mycoses and, as might be expected at this early stage of development, optimal dosage and duration of treatment for some serious mycoses is not yet established. Further study to evaluate higher dosages and to establish the efficacy of fluconazole relative to more established antifungal agents is required. In patients with oropharyngeal or oesophageal candidiasis, fluconazole produces rapid relief and eradicates the yeast in 50 to 90% of patients. Relapse of oral infection is common in chronically immunocompromised patients regardless of the antifungal used, and adequate primary therapy plus long term prophylaxis appears necessary in patients with AIDS. A single oral dose of fluconazole was comparable to standard topical azole therapy in women with acute vaginal candidiasis. Preliminary reports of success against deep-seated candidiasis are encouraging; moreover, experience in noncomparative clinical trials suggests that fluconazole 200 to 400mg once daily resolves infection in the majority of seriously ill patients. Clinical improvement has been reported in a few cases of pulmonary Aspergillus infection but the overall efficacy of conventional dosages of fluconazole in this mycosis has not been as impressive. Early experience in coccidioidosis, predominantly meningitis, suggests a beneficial clinical effect with oral fluconazole in this difficult to treat mycosis but relapse remains a problem. Fluconazole is a promising treatment of cryptococcal meningitis. The rate of clinical resolution and eradication of Cryptococcus neoformans from cerebrospinal fluid has been similar between fluconazole and amphotericin B treatment groups in comparative trials. Comparative trials of maintenance therapy indicate a similar low rate of relapse among patients given oral fluconazole once daily and intravenous amphotericin B once weekly. However, these results are preliminary and further study is required. Fluconazole has been well tolerated to date but wider clinical experience is needed, especially with regard to the rate occurrence of hepatotoxicity and exfoliative skin reactions. The promising clinical response of patients with various forms of candidiasis or cryptococcosis -together with convenient administration regimens--recommends fluconazole as a useful addition to currently available systemic antifungal therapies, in particular for the treatment of mycoses in patients with AIDS. PMID- 2196168 TI - Pinacidil. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the treatment of hypertension. AB - Pinacidil is an orally administered antihypertensive drug that acts via direct relaxation of vascular smooth muscle to produce peripheral vasodilatation and a reduction in blood pressure without significant direct effects on cardiac electrophysiology. Pinacidil is unrelated to other antihypertensive drugs in clinical use, either in structure or mechanism of action. It belongs to a new class of agents called 'potassium channel openers' which act via potassium efflux to hyperpolarize cell membranes, indirectly causing a net reduction in intracellular calcium that leads to relaxation of vascular smooth muscle. Pinacidil is indicated in the management of essential hypertension. In clinical trials of up to 1 year duration, pinacidil administered twice daily in a controlled release capsule formulation has been shown to achieve adequate blood pressure control both in previously untreated patients and in those with blood pressure inadequately controlled by beta-adrenoceptor blocking drugs or thiazide diuretics. In long term (up to 1 year) comparative studies pinacidil was at least as effective as hydralazine, prazosin or nifedipine in maintaining blood pressure control. Pinacidil may also have a potential use in the treatment of patients with secondary renal hypertension. Clinical trials to date have usually allowed the addition of a thiazide diuretic and/or beta-adrenoceptor blocking drug to enhance the efficacy of pinacidil and/or to reduce the incidence of adverse effects. The main adverse effects of pinacidil treatment, which result from its peripheral vasodilator activity, are headache, oedema, palpitations and tachycardia. Although the overall incidence of adverse effects is quite high, they are usually mild, transient in nature and respond to a reduction in dose. Nevertheless, these effects may occasionally be severe, necessitating withdrawal from therapy. Thus, pinacidil is an effective antihypertensive drug for the treatment of mild to moderate essential hypertension. Despite its novel mechanism of action pinacidil causes adverse effects typical of peripheral vasodilators; during long term use with twice daily administration of the controlled release capsule formulation, the addition of a diuretic is often necessary to attenuate peripheral oedema and maintain adequate control of blood pressure. Further long term controlled trials are needed to determine the precise role of pinacidil relative to that of the angiotensin converting enzyme (ACE) inhibitors and calcium channel blocking drugs. PMID- 2196170 TI - Refractory epilepsy: an evaluation of psychological methods in outpatient management. AB - Two groups of adult outpatients (n = 19 and n = 21) with poorly controlled epilepsy and significant psychological disorder, assessed in terms of rating scales, received two psychological treatments in a balanced cross-over design after stable baseline seizure frequency had been established. A third group (n = 19), who had poorly controlled epilepsy but no significant psychological disturbance received one type of psychological treatment after a stable baseline. The treatments were educational and were designed to improve coping skills. Weekly seizure frequency was monitored for 42 weeks, and self-rating measures of anxiety and depression were obtained before treatment and at the end of follow up. All three groups showed a significant reduction in seizure frequency that was maintained at 6-month follow-up. The two groups with psychological symptoms showed a significant improvement in scores on the self-rating scales. We concluded that routine use of psychological intervention may be helpful in outpatient management of epilepsy. PMID- 2196171 TI - Refined crystal structure of the triphosphate conformation of H-ras p21 at 1.35 A resolution: implications for the mechanism of GTP hydrolysis. AB - The crystal structure of the H-ras oncogene protein p21 complexed to the slowly hydrolysing GTP analogue GppNp has been determined at 1.35 A resolution. 211 water molecules have been built into the electron density. The structure has been refined to a final R-factor of 19.8% for all data between 6 A and 1.35 A. The binding sites of the nucleotide and the magnesium ion are revealed in high detail. For the stretch of amino acid residues 61-65, the temperature factors of backbone atoms are four times the average value of 16.1 A2 due to the multiple conformations. In one of these conformations, the side chain of Gln61 makes contact with a water molecule, which is perfectly placed to be the nucleophile attacking the gamma-phosphate of GTP. Based on this observation, we propose a mechanism for GTP hydrolysis involving mainly Gln61 and Glu63 as activating species for in-line attack of water. Nucleophilic displacement is facilitated by hydrogen bonds from residues Thr35, Gly60 and Lys16. A mechanism for rate enhancement by GAP is also proposed. PMID- 2196172 TI - Efficient translocation of positively charged residues of M13 procoat protein across the membrane excludes electrophoresis as the primary force for membrane insertion. AB - The coat protein of bacteriophage M13 is inserted into the Escherichia coli plasma membrane as a precursor protein, termed procoat, with a typical leader peptide of 23 amino acid residues. Its membrane insertion requires the electrochemical potential but not the cellular components SecA and SecY. Since the electrochemical gradients result in the periplasmic side of the membrane being positively charged, the membrane potential could contribute to the transfer of the negatively charged central region of procoat across the membrane. Here we demonstrate that the central domain following the leader peptide can be translocated across the membrane even when the net charge of the region is changed from -3 to +3. This rules out an electrophoresis-like insertion mechanism for procoat. We also show that the sec independence of procoat insertion is linked to the presence of the second apolar domain. The deletion of most of the second apolar domain from a procoat fusion protein results in sec dependent membrane insertion of the hybrid protein. Moreover, like other proteins that require the sec genes, translocation of this sec dependent procoat protein is inhibited when positively charged residues are introduced after the leader peptide. Loop models involving one or two hydrophobic regions are presented that account for the differences in tolerance of positively charged residues. PMID- 2196173 TI - Colony-stimulating factor 1 activates protein kinase C in human monocytes. AB - Colony-stimulating factor 1 (CSF-1) is required for the survival, proliferation and differentiation of monocytes. We previously demonstrated that the CSF-1 receptor is linked to a pertussis toxin-sensitive G protein and that the induction of Na+ influx by CSF-1 is a pertussis toxin-sensitive event. The present studies have examined activation of protein kinase C as a potential intracellular signaling event induced by the activated CSF-1 receptor. The results demonstrate that CSF-1 stimulates translocation of protein kinase C activity from the cytosol to membrane fractions. This activation of protein kinase C was sensitive to pretreatment of the monocytes with pertussis toxin. Lipid distribution studies demonstrated that phosphatidylcholine (PC) is the major phospholipid in human monocytes. Moreover, the results indicate that CSF-1 stimulation is associated with decreases in PC, but not in phosphatidylinositol (PI), levels. The absence of an effect of CSF-1 on PI turnover was confirmed by the lack of changes in inositol phosphate production. In contrast, CSF-1 stimulation was associated with increased hydrolysis of PC to phosphorylcholine and diacylglycerol (DAG) in both intact monocytes and cell-free assays. Furthermore, the increase in PC turnover induced by CSF-1 was sensitive to pertussis toxin. The results also demonstrate that the induction of Na+ influx by CSF-1 is inhibited by the protein kinase C inhibitors staurosporine and the isoquinoline derivative H7, but not by HA1004.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196174 TI - Svp25, a synaptic vesicle membrane glycoprotein from Torpedo electric organ that binds calcium and forms a homo-oligomeric complex. AB - Svp25 is a major glycoprotein of cholinergic synaptic vesicles isolated from the Torpedo electric organ. On SDS-PAGE svp25 migrates as a protein of Mr 25,000 and on two dimensional gel electrophoresis separates into several isoforms around a pI of 6.0. It binds concanavalin A and on phase separation with Triton X-114 behaves as an integral membrane protein. Svp25 represents a major vesicular 45Ca2(+)-binding protein. Under non-reducing conditions svp25 forms complexes of higher molecular weight which are multiples of 25,000. Svp25 is contained in the dense web of nerve terminal ramifications at the ventral side of the electroplaque cells. Colloidal gold labelling using a monospecific antibody confirms the selective association of the protein with synaptic vesicles. Although the function of the vesicular svp25 glycoprotein is not known, its ability to bind Ca2+ suggests that it is regulated by activation of the nerve terminal. PMID- 2196175 TI - Role of trans-activating proteins in the generation of active chromatin at the PHO5 promoter in S. cerevisiae. AB - Induction of the PHO5 gene in Saccharomyces cerevisiae by phosphate starvation was previously shown to be accompanied by the removal of four positioned nucleosomes from the promoter. We have now investigated the role of two trans activating proteins, encoded by PHO2 and PHO4, which bind to the PHO5 promoter. Both proteins are absolutely required for the chromatin transition to occur as shown by analysis of null mutants of the two genes. Transformation of these mutant strains with plasmids containing the respective genes restores the wild type chromatin response. Increasing the gene dosage of PHO2 and of PHO4 makes it possible to differentiate functionally between the two proteins. From over expressing PHO4 in a wild type and also in a pho2 null mutant strain and complementary experiments with PHO2, it is concluded that the PHO4 protein is the primary trigger for the chromatin transition, consistent with one of its two binding sites being located between positioned nucleosomes in repressed chromatin and thereby accessible. PHO2, the binding site of which is located within a nucleosome under conditions of PHO5 repression, contributes to the chromatin transition either by destabilizing histone-DNA interactions or by under-going interactions with PHO4. PMID- 2196176 TI - Multiple cDNA clones encoding nuclear proteins that bind to the tax-dependent enhancer of HTLV-1: all contain a leucine zipper structure and basic amino acid domain. AB - A trans-activator protein, p40tax, of human T cell leukemia virus type 1 (HTLV-1) activates its own promoter and cellular promoters of IL-2, IL-2 receptor alpha and GM-CSF genes. We isolated three cDNA clones encoding cellular proteins that bind to the p40tax-dependent enhancer of HTLV-1 by screening a lambda gt11 cDNA library of an HTLV-1 infected cell line. All three proteins, TREB5, TREB7 and TREB36, contained a leucine zipper structure and basic amino acid domain, which are conserved in FOS, JUN and CREB, and also had multiple potential phosphorylation sites. The proteins expressed in Escherichia coli bound to the p40tax-dependent enhancer of the 21 bp sequence, but not to an inactive mutant carrying a mutation in the CRE region. In DNase I footprint analysis, all three proteins protected the 21 bp sequences in the LTR; however, the patterns were not identical to each other. TREB7 and TREB36 protected all three repeats of the 21 bp, but TREB5 protected only the second repeat. TREB7 and TREB36 protected the 5' and middle portions of the 21 bp which are essential for p40tax-mediated trans activation, whereas TREB5 and CREB1 protected a narrower part of the middle region of the second 21 bp repeat containing the CRE consensus sequence. These structural features and DNA binding properties suggest that TREB proteins are members of a CREB protein family and that some of them (i.e., TREB7 and TREB36) may be involved in p40tax-mediated trans-activation. PMID- 2196177 TI - A single base mutation at position 2661 in E. coli 23S ribosomal RNA affects the binding of ternary complex to the ribosome. AB - A single base substitution mutation from guanine to cytosine was constructed at position 2661 of Escherichia coli 23S rRNA and cloned into the rrnB operon of the multi-copy plasmid pKK3535. The mutant plasmid was transformed into E.coli to determine the effect of the mutation on cell growth as well as the structural and functional properties of the mutant ribosomes in vivo and in vitro. The results show that the mutant ribosomes have a slower elongation rate and an altered affinity for EF-Tu-tRNA-GTP ternary complex. This supports previous findings which indicated that position 2661 is part of a region of 23S rRNA that forms a recognition site for binding of the ternary complex in the ribosomal A site. Combinations of the 2661 mutation with various mutations in ribosomal protein S12 also demonstrate that elements of both ribosomal subunits work in concert to form this binding site. PMID- 2196178 TI - Human T cell proliferative responses to Plasmodium vivax antigens: evidence of immunosuppression following prolonged exposure to endemic malaria. AB - Human T cell proliferative responses, of 33 adult Sri Lankans convalescing from Plasmodium vivax infections, to several P. vivax antigens (i.e. a soluble extract of asexual erythrocytic stage parasites and two cloned antigens that are potential vaccine candidates PV200 and GAM-1) were assessed. The peripheral blood mononuclear cell proliferative responses to the soluble extract of P. vivax, as assessed by studying both the proportion of responders and the degree of the response, were significantly lower in a group of individuals resident in a malaria endemic area in Sri Lanka than in another group that did not have a life long exposure to malaria but had acquired the disease on a visit to an endemic region. Individuals of both groups responded equally well to mitogen. The responses to a non-malarial antigen such as purified protein derivative of tuberculin were only marginally lower in residents of the malaria-endemic region. These findings suggest that exposure to endemic P. vivax malaria leads to a specific immunosuppression to P. vivax antigens. Immunosuppression of a much lower degree was evident to a non-malarial antigen. PMID- 2196179 TI - Synthesis of tetrahydrobiopterin in Friend erythroleukemia cells and its modulator effect on cell proliferation. AB - The induction of the enzymes in the tetrahydrobiopterin pathway by dimethyl sulfoxide (DMSO) was investigated in subclones F4N and B8/3 of the proerythroblastoid Friend erythroleukemia cell line (MEL). GTP-cyclohydrolase, the initial enzyme in the biosynthetic pathway, is virtually absent in both clones, but expression increases during 3 days of DMSO treatment. The final enzyme levels show 12-fold (subclone B8/3) and 40-fold (subclone F4N) increases compared to initial values. Enhancement of 6-pyruvoyl tetrahydropterin synthase activity is detectable 6 h after exposure to DMSO and continues to increase in the 3-day time period to 2.4-fold and 1.8-fold levels in subclones B8/3 and F4N, respectively. Sepiapterin reductase is present in unstimulated F4N cells and absent in B8/3 cells. The enzyme activity is not affected by DMSO treatment in either cell line. This explains why DMSO treatment causes accumulation of tetrahydrobiopterin in the MEL subclone F4N, but not in subclone B8/3. MEL cells are devoid of phenylalanine hydroxylase for which tetrahydrobiopterin serves as cofactor. In F4N, but not in B8/3, tetrahydrobiopterin modulates the rate of [3H]thymidine incorporation, thus being functionally linked with cell proliferation rather than with differentiation. In contrast to T lymphocytes, periods of tetrahydrobiopterin synthesis and of modulator function are uncoupled in MEL cells. PMID- 2196180 TI - Expression of spasmolysin (FIM-A.1): an integumentary mucin from Xenopus laevis. AB - In the past, a unique type of precursor for a secretory protein was discovered. It contains a central repetitive domain rich in threonine residues and terminal cysteine-rich domains. Due to striking homologies of these terminal domains with pancreatic spasmolytic polypeptide, originally the name "prepro-spasmolysin" was proposed. Here we show that the mature protein has a MW of about 130 kDa, consisting of about 70% carbohydrate and 30% protein. Similar O-linked glycoproteins have been found in mucins from human intestine. For this and numerous other reasons we decided to rename this glycoprotein "frog integumentary mucin A.1" (FIM-A.1). Furthermore, analysis of the protein with specific antibodies against the predicted C-terminal end indicates that FIM-A.1 is probably not processed at pairs of basic residues. In situ hybridization as well as immunofluorescence studies revealed that FIM-A.1 is expressed and stored exclusively in mature mucous glands of Xenopus laevis skin. Only cone cells at the proximal part of these glands do not synthesize FIM-A.1. In contrast, all other physiologically active peptides from X. laevis skin investigated so far are synthesized in granular glands. A hypothetical function of FIMs for defense against microbial infections is discussed. PMID- 2196181 TI - Tissue-specific distribution of a novel component of epithelial basement membranes. AB - Monoclonal antibodies against basement membrane (BM) were generated using the matrix deposited by cultured rabbit corneal epithelial cells as immunogen. BM antibodies were identified by immunofluorescent staining of frozen tissue sections and of extracellular matrix of living cultured cells. BM localization was confirmed by immunoelectron microscopy. Antibody AE26 immunoprecipitates a 140,000 Mr component from radiolabeled corneal epithelial cells and recognizes this component plus a 95,000 Mr band on Western blots. The antigen resists extraction by high and low salt and by nonionic detergents, but is solubilized in 4 M urea/1% mercaptoethanol. On isoelectric focusing and nonequilibrium pH gradient gels, AE26 antigen migrates to the acidic region (pI less than 3). The molecule is destroyed by trypsin, but is insensitive to bacterial collagenase. In frozen tissue sections, AE26 stains only BM of stratified epithelia plus trachea, ureter, lung, and intestine, but no other epithelial or nonepithelial BM. AE26 antigen is detected on Western blots of cornea, skin, and lung extracts, but not liver, kidney, or muscle, indicating that this is not due to masking of the epitope. This tissue distribution is different from any previously described BM molecule. Although we have not ruled out the possibility that AE26 recognizes a modification or fragment of a known BM component (particularly entactin), the acidic pI, collagenase resistance, and unusual tissue specificity suggest that AE26 recognizes a new BM protein. The BM heterogeneity demonstrated by AE26 may play a structural role or provide positional signals to the overlying epithelium. PMID- 2196182 TI - Effects of dexamethasone on multiplication and differentiation of rat adipose precursor cells. AB - The effects of dexamethasone (DEX) on adipose precursor cells from rat adipose tissue were studied in primary culture. When added from the beginning of culture in media containing untreated fetal calf serum (SM), serum treated with charcoal to remove steroid hormones (CSM), or serum-free medium (SFM), DEX inhibited cellular growth. Lipoprotein lipase (LPL) as well as glycerophosphate dehydrogenase (GPDH) activities, markers of cellular differentiation, were also inhibited, except in CSM where LPL was stimulated. When added after cellular confluence, however, DEX had opposite effects and now stimulated cellular differentiation. This effect was highly dependent on insulin. These studies demonstrate that DEX affects adipose precursor cells in several ways, depending on the type of culture medium, the time period of exposure, and the presence of insulin. PMID- 2196183 TI - Glucoregulatory responses of adult and aged rats after exposure to chronic stress. AB - Stress has been implicated as an environmental factor that may accelerate the process of biological aging. However, this proposal has remained largely anecdotal due to relatively few studies that directly tested this hypothesis. In the present experiments groups of 6-month-old and 20-month-old male F-344 rats were chronically stressed for a six-month period. After the last stress session, when the animals were 12 months of age (adult) and 26 months of age (old), control and chronically stressed rats were tested for their ability to: (a) elicit glucose and insulin responses to an acute, novel stressor; (b) remove a circulatory glucose load elicited either by acute stress exposure or by injection of d-glucose; and (c) raise insulin levels after a glucose challenge. In control rats, we observed a deficit in each of these parameters in old compared to adult rats. Exposure to chronic stress did not exacerbate deterioration of these response mechanisms in either adult or old rats. In fact, the data showed a modest improvement in glucose tolerance in chronically stressed compared to age matched control rats. We conclude that chronic stress did not exacerbate age dependent decline of glucoregulatory capacity. From these results and from our earlier work, we speculate that the decline during aging of the functional integrity of systems involved in the response to stress may be sustained by periodic challenges from the organism's external environment. PMID- 2196184 TI - GM-CSF expands the eosinophilic compartment in chronic idiopathic neutropenia. PMID- 2196185 TI - [The chronopharmacology of the antidepressants]. AB - The conception of the specific activity of antidepressants is considered from the chronobiological positions. Depression can be based on phasic dissociation between different periods and first of all circadian fluctuation of some physiological functions. Various antidepressants modified biorhythms and promoted their resynchronization. This action probably depended on its influence on the activity of the cerebral pacemaker structures (suprachiasmatic nuclei, hypothalamus and pineal gland). PMID- 2196186 TI - [New concepts of nephron function and the mechanisms of action of diuretics]. AB - The hypothesis of gate charges of intracellular junctions of nephron wall is proposed. According to the hypothesis, negative charges at the entrance of the channel fixed on the lumenal side of nephron epithelium permit cation entry and block anion flow in the channel. The interaction of ions and fixed charges with sodium leads to increased reabsorption of various cations including sodium and also enhanced excretion of chloride and hydrogen ions in the urine resulting from osmotic fluid and ion diffusion through intracellular junctions. Mercurial diuretics, ethacrynic acid and osmotic agents but not furosemide enhance permeability of intracellular junctions for ions and eliminate the selective function of the fixed charges. PMID- 2196187 TI - Ontogenic maturation of the immune system in reptiles. PMID- 2196188 TI - A 12 kDa protein in chicken serum antigenically cross-reactive with, but unrelated to, beta 2-microglobulin. AB - A protein, isolated from chicken serum, showed the following beta 2-microglobulin like properties; an apparent molecular size of 12000 Mr, predominantly beta-sheet secondary structure, and antigenic cross-reaction with human beta 2 microglobulin. However, amino acid composition analysis and partial amino acid sequence analysis showed that this molecule was not only not a beta 2 microglobulin, but was unrelated to any other known class of protein. PMID- 2196189 TI - [Autonomic cardiac neuropathy in diabetics: methods of research and practical interest]. PMID- 2196190 TI - Effect of the insulin degradation inhibitors bacitracin and chloroquine on insulin binding data to H35 rat hepatoma cells. AB - The influence of correction for internalization and of inhibition degradation by the use of bacitracin or chloroquine on the insulin binding data of H35 rat hepatoma cells has been assessed. Internalized insulin represented about 50% of total cell bound insulin at tracer concentration and is not affected by bacitracin or chloroquine. The use of the insulin degradation inhibitors bacitracin and chloroquine resulted in Scatchard plots that were strikingly less curvilinear than control cells (as indicated by a decreased K1/K2 ratio (p less than 0.001) and Ke/Kf ratio (p less than 0.01)). In the two site model there was a significant increase in the number of high affinity binding sites concomitant with a significant decrease in the high affinity association constant; there was also a significant decrease in the number of the low affinity binding sites. The total number of binding sites did not change. For the negative cooperativity model the use of each drug resulted in a significant increase in the affinity constant of the filled site. These results indicate that insulin degradation induces negative cooperativity and that the results are inconsistent with the two site model. PMID- 2196192 TI - Low molecular weight heparin restores antithrombin III activity from hyperglycemia induced alterations. AB - Alteration of antithrombin III (ATIII) activity, glycemia level dependent, exists in diabetes mellitus. In this study the ability of a low molecular weight heparin (LMWH) (Fluxum, Alfa-Wassermann S.p.A., Bologna, Italy), as well as unfractioned heparin, to preserve ATIII activity from glucose-induced alterations, both in vitro and in vivo, is reported. The subcutaneous and intravenous LMWH and heparin administration increases basal depressed ATIII activity in diabetic patients. Heparin shows an equivalent effect on both anti-IIa and anti-Xa activity of ATIII, while LMWH is more effective in preserving the anti-Xa activity. Similarity, heparin preserves ATIII activity from hyperglycemia-induced alterations, during hyperglycemic clamp, and LMWH infusion is able to preserve a significant amount of anti-Xa activity from glucose-induced alterations. Since diabetic patients show a high incidence of thrombotic accidents, LMWH appears to be a promising innovation for the prevention of diabetic thrombophylia. PMID- 2196191 TI - Effect of short term fasting on glucose tolerance and insulin secretion: influence of the initial glucose level. AB - To evaluate the effect of fasting on glucose tolerance (GT) and insulin secretion, a 5 h oral glucose tolerance test was performed after an overnight fast and after 3-6 days of fasting in 66 obese subjects presenting a normal (n = 22), impaired (n = 23) or diabetic (n = 21) GT. Insulin secretory capacity was assessed using two glucose-independent parameters of beta cell function. In the normal group, fasting induced a fall in basal glycemia from 84 +/- 1 to 58 +/- 2 mg/dl (P less than 0.001) and an increase in the area of glucose (+58 +/- 8%, P less than 0.001), insulin (+75 +/- 10%; P less than 0.001) and C-peptide (+58 +/- 10%; P less than 0.001) during OGTT, these responses were consistent with the emergence of insulin resistance. The insulin secretory capacity was significantly decreased. In the diabetic group, fasting was associated with an increase in insulin (+34 +/- 10%; P less than 0.005) and C-peptide (+34 +/- 8%; P less than 0.001) responses to OGTT despite a reduction in basal glycemia from 174 +/- 11 to 86 +/- 4 mg/dl (P less than 0.001) and in glucose response (-20 +/- 3%; P less than 0.001), indicating an improvement of insulin secretory capacity. In the group with impaired GT, basal glycemia decreased from 97 +/- 2 to 70 +/- 2 mg/dl (P less than 0.001) but glucose, insulin and C-peptide curves were not significantly affected by fasting.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196194 TI - Selections from current literature: chronic fatigue syndrome. PMID- 2196193 TI - [Effect of glipizide on glycemic control and peripheral insulin sensitivity in type 1 diabetics]. AB - To assess the effect of Glipizide on glycaemic control and peripheral insulin sensitivity, 9 type 1 (insulin dependent) diabetic patients with normal BMI, mean age 42.1 +/- 11.0 years, diabetes duration 16.3 +/- 9.2 years were studied. They were treated by continuous subcutaneous insulin infusion for a mean duration of 32.2 +/- 11.0 months, they were in good glycaemic control (mean HbA1 7.9 +/- 1.2%, upper limit of normal value 7.5%). In a double blind randomized control study they were successively allocated for a three month period to 15 mg of Glipizide daily or a Placebo. At the end of each period the following parameters were recorded: HbA1, mean plasma glucose levels, daily insulin dosage: basal rate and pre prandial bolus, peripheral insulin sensitivity assessed by euglycaemic hyperinsulinic clamp technique, the addition of Glipizide did not induce any statistically significant modification of HbA1, glycaemic values, and daily insulin dosage: basal rate 18.2 +/- 8.7 vs. 17.9 +/- 7.3 IU/24 hours and pre prandial bolus 18.6 +/- 7.0 vs 17.6 +/- 6.3 IU/24 hours. During the glucose clamp, glucose uptake was similar under Glipizide or Placebo with the 3 levels of insulin infused. These results suggest that in type 1 diabetic patients the addition of Glipizide to insulin therapy does not alter glycaemic control and peripheral insulin sensitivity. PMID- 2196195 TI - [Scleroderma (progressive systemic sclerosis)]. PMID- 2196196 TI - [Immunity of the "deep lung"]. PMID- 2196197 TI - [Zolpidem tartrate]. PMID- 2196198 TI - [Hypoglycemia]. PMID- 2196200 TI - [Photodynamic therapy in gastroenterology]. PMID- 2196199 TI - [Neonatal thrombocytopenia caused by fetomaternal alloimmunization: clinical, immunological and therapeutic aspects]. PMID- 2196201 TI - Sick building syndrome: acute illness among office workers--the role of building ventilation, airborne contaminants and work stress. AB - Outbreaks of acute illness among office workers have been reported with increasing frequency during the past 10-15 years. In the majority of cases, hazardous levels of airborne contaminants have not been found. Generally, health complaints have involved mucous membrane and respiratory tract irritation and nonspecific symptoms such as headache and fatigue. Except for rare examples of hypersensitivity pneumonitis related to microbiologic antigens, there have been no reports of serious morbidity or permanent sequelae. However, the anxiety, lost work time, decreased productivity and resources spent in investigating complaints has been substantial. NIOSH has reported on 446 Health Hazards Evaluations that were done in response to indoor air complaints. This data base is the source of most of the published accounts of building-related illness. Their results are summarized here with a discussion of common pollutants (tobacco smoke, formaldehyde, other organic volatiles), and the limitations of the available industrial hygiene and epidemiologic data. There has been one large scale epidemiologic survey of symptoms among office workers. The results associate risk of symptoms to building design and characteristics of the heating/air conditioning systems, consistent with the NIOSH experience. Building construction since the 1970s has utilized energy conservation measures such as improved insulation, reduced air exchange, and construction without opening windows. These buildings are considered "airtight" and are commonly involved in episodes of building-associated illness in which no specific etiologic agent can be identified. After increasing the percentage of air exchange or correcting specific deficiencies found in the heating/air-conditioning systems, the health complaints often resolve, hence, the term "tight building syndrome" or "sick building syndrome."(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196202 TI - Through the centuries with food and drink, for better or worse. VI. PMID- 2196203 TI - Observations on heaves. An asthma-like syndrome in the horse. 1964. AB - Observations in six horses with heaves established a clear relationship between attacks of heaves and the feeding of hay. Severe acute attacks were accompanied by striking changes in the eosinophil count and the sedimentation rate. The variation in the severity of heaves in relation to the feeding and withholding of hay is accounted for by assuming that attacks result from a transient, obstructive lesion in the bronchial tree or lung caused by hypersensitivity to some component of hay. The observations strongly suggest that heaves is a respiratory allergic disease in the horse. The relation of heaves to pulmonary emphysema in the horse is discussed. PMID- 2196204 TI - Genetic analysis of polymorphic proteins of the human malaria parasite Plasmodium falciparum. AB - Five polymorphic proteins, detected by two-dimensional electrophoresis, were analysed in the parents and progeny of a cross between two clones of the malaria parasite Plasmodium falciparum. The information obtained showed that different forms of each protein were determined by allelic variants of each respective gene. One protein was identified as the parasite enzyme adenosine deaminase. Recombinant parasites were produced at a higher than expected frequency. PMID- 2196205 TI - Practical advice for the gastroenterologist dealing with symptomatic HIV disease. PMID- 2196206 TI - Nutcracker, neurosis, or sampling bias? PMID- 2196207 TI - Heat probe thermocoagulation and pure alcohol injection in massive peptic ulcer haemorrhage: a prospective, randomised controlled trial. AB - We conducted a prospective randomised controlled trial of 137 patients with massive peptic ulcer haemorrhage over a period of 12 months to compare the haemostatic effects of endoscopic heat probe thermocoagulation and pure alcohol injection. Seventy eight patients (56.9%) were in shock at the time of randomisation to the trial. The age, sex, number of patients in shock, haemoglobin value at the time of entry to the trial, number of patients with severe medical illness, location of bleeders, and stigmata of recent haemorrhage were comparable among the heat probe, pure alcohol, and control groups. The initial haemostatic effect of the heat probe was better than that of the pure alcohol injection (44 of 45 v 31 of 46, p = 0.0004). The ultimate haemostasis achieved by the heat probe group (41 of 45) was better than that of the pure alcohol group (31 of 46, p = 0.012) and of controls (24 of 46, p = 0.0001). The duration of hospital stay was shorter for patients in the heat probe group than for the control group (6.2 days v 13.8 days, p less than 0.05). The incidence of emergency surgery was less for the heat probe than the control group (three of 45 v 12 of 46, p = 0.027). The mortality rate was less in the heat probe than in the control group (one of 45 v seven of 46, p = 0.031). We suggest that heat probe thermocoagulation should be the first treatment of choice for arrest of massive peptic ulcer haemorrhage. PMID- 2196209 TI - Study on the population of the warble fly, Oestromyia leporina (Pallas. 1778) (Diptera, Hypodermatidae) in Bohemia. AB - A new population of the warble fly, Oestromyia leporina from Western Bohemia is described. The parasite was recorded on Microtus arvalis and M. agrestis. The infection of offspring in the den did not occur. PMID- 2196208 TI - Sucralfate in the treatment and prevention of gastric ulcer: multicentre double blind placebo controlled study. AB - A randomised controlled multicentre trial was performed in 160 patients with gastric ulcer, proved by endoscopy and biopsy, to compare ulcer healing with sucralfate and ranitidine (double blind double dummy design) and to assess the effect of maintenance treatment with sucralfate on ulcer recurrence (double blind placebo controlled design). The healing rates were similar with 4 g sucralfate suspension per day and 300 mg ranitidine per day (82% and 88% after 12 weeks, respectively). Of the 109 patients with healed ulcers, 92 were entered into the maintenance trial and treated with sucralfate tablets (2 g per day) or placebo tablets. Maintenance treatment with sucralfate delayed symptoms of gastric ulcer recurrence. Lifetable analysis showed significant differences between sucralfate and placebo, both after six months (p = 0.018) and after 12 months (p = 0.044). The rates of symptom recurrences were 13% and 34% after six months and 34% and 55% after 12 months for sucralfate and placebo, respectively. The rate of asymptomatic recurrences after 12 months was similar in the two groups (9% and 10%, respectively). The recurrence rate was higher in patients who had never taken non-steroidal anti-inflammatory drugs than in those who had but had stopped on admission to the study. It was also higher in patients with recurrent ulcer and in those with scarring deformation and narrowing of the pylorus. Maintenance treatment with sucralfate slowed the appearance of symptom recurrences of gastric ulcer. PMID- 2196210 TI - [Angiographic studies on the effects of a novel calcium antagonist AE0047 on cerebral arteries in dogs, with special reference to the preventive effects of AE0047 on cerebral vasoconstriction induced by endothelin]. AB - AE0047, a novel calcium antagonist, has mild and long-acting hypotensive effects. This drug also has more selective dilating action on cerebral arteries than on other systemic ones. We studied the cerebral vasodilatative effects of AE0047 by means of vertebral angiography in anesthetized dogs. Vertebral blood flow (VBF) was significantly increased by 91, 139 and 132% in 10, 30 and 60 min after intravenous administration of AE0047 at 30 micrograms/kg, respectively. No difference in vasodilating action was observed among basilar, posterior communicating, middle cerebral and internal carotid arteries. In basilar artery, the dilatative rate was about 30% between 10 and 60 min after injection of AE0047. Following intravertebral administration of endothelin at 100 pmol/kg, small vessels of the cerebral artery were constricted, and VBF was gradually decreased. AE0047 eliminated the vasoconstriction and increased VBF. Moreover, the vasoconstrictive effect of endothelin was prevented by pre-treatment of AE0047. These results indicate that AE0047 has potent vasodilating and spasmolytic actions on cerebral arteries. PMID- 2196211 TI - New AHA general counsel wants better business climate. PMID- 2196212 TI - Hospital chaplain pioneers new cancer support programs. PMID- 2196213 TI - Centromeric heterochromatin instability of chromosomes 1, 9, and 16 in variable immunodeficiency syndrome--a virus-induced phenomenon? AB - Centromeric instability of chromosomes 1, 9, and 16 has been described in eight patients with variable immunodeficiency. Although the pathogenetic relationship of these cytogenetic abnormalities with the clinical symptoms are unclear, it has nevertheless been proposed that they are a hallmark of this syndrome. Based on the clinical, immunological and cytogenetic data from the literature, a model is presented suggesting that the cytogenetic changes are not causatively involved in the immunodeficiency syndrome, but result from specific virus infections occurring as a consequence of the immunodeficiency in genetically predisposed individuals. PMID- 2196214 TI - The inaccessibility of the outer membrane of adherent Treponema pallidum (Nichols strain) to anti-treponemal antibodies, a possible role of serum proteins. AB - Fresh and aged adherent T pallidum were used to study the accessibility of their outer membrane to antibodies by means of an indirect immunofluorescent technique. The integrity of the outer membrane was demonstrated by the non-reactivity with a monoclonal antibody directed against the axial filaments. Using the sera from patients with sero-positive primary and secondary syphilis no binding of IgG and IgM antibodies was observed. However, IgG and IgM antibody fractions isolated from the sera of patients with secondary syphilis, gave with the fresh fibroblast adhering treponemes a mean of 14.5% IgG- and of 43.2% IgM positive treponemes. These means were 32.1% and 87.3% respectively for aged treponemes. Lower percentages were observed when fibronectin adhering treponemes were used. This demonstrates the inability of the outer membrane to bind antibodies in a majority of the fresh treponemes. This is partly lost on in vitro aging. Absence of IgG- and IgM fluorescence was also observed when sequential incubations with the antibody fractions and control sera were used. This was accompanied by the deposition of the third complement factor (C3) around the treponemes. Incubations of IgG- or IgM pre-coated adherent treponemes with heat-inactivated control sera or a C3 deficient serum did not result in the deposition of C3, and partially restored the detection of human antibodies. The most likely explanation for the absence of fluorescence is that antibodies become buried in an extra-cellular layer of serum proteins. The deposition of C3 from control sera alone most probably points to the classical pathway of complement activation and suggests that antibodies of rabbit origin constitute a part of the extracellular layer of treponemes. PMID- 2196215 TI - Anti-Treponema pallidum IgM, IgA, and IgG subclass antibody responses after treatment in patients with syphilis at various stages: 1. Assessments by enzyme linked immunosorbent assay. AB - Patients with syphilis at various stages were followed from the beginning by serial measurements of antibodies against Treponema pallidum that belonged to the classes IgM and IgA, and to the subclasses IgG1 to 4 by an enzyme-linked immunosorbent assay. A marked decrease in levels of antibodies was noted within three months after treatment. In the case of IgM this occurred in 19 of the 31 patients studied (61%), in the case of IgA in 15 patients (48%) and in the case of one or more of the subclasses of IgG in 18 patients (52%). These findings indicate the usefulness of levels of IgM antibodies as markers for evaluating the effects of treatment. There were, nevertheless, 12 patients (39%) whose levels of IgM antibodies remained consistently below the normal limits or failed to decline despite treatment. In five (16%) of these cases, the serum level of IgA antibodies or of one or more subclasses of IgG fell after treatment. The results suggest the potential usefulness of IgA antibodies in the various IgG subclasses as a marker for evaluating the results of treatment in those patients whose levels of IgM antibodies do not change in response to treatment. PMID- 2196216 TI - Genital infections in women attending a genito-urinary clinic in Harare, Zimbabwe. AB - One hundred women attending a sexually transmitted diseases clinic in Harare were examined for presenting features and genital infections. The most common presenting symptoms were of discharge, lower abdominal pain and dysuria, and on examination signs of discharge, inflammation, haemorrhage or ulcers/erosions were noticeable in all women. Fourteen women had genital warts. Pathogens were detected in 95% of patients. Gonococcal infection occurred in 19 women, with 60% of the strains isolated being penicillinase producing. Yeasts were detected in specimens from 25 women while chlamydial infection appeared to be rare, evidence of infection being detected in only eight women. Sera from 44 women were positive by the RPR test and sera from 33 women were positive by TPHA. Gardnerella vaginalis was isolated from 48 women, Group B streptococci from 37 women, and Trichomonas vaginalis from 32 women. PMID- 2196217 TI - Syphilis in art: an entertainment in four parts. Part 3. PMID- 2196218 TI - The choice of microscopes for use in genitourinary medicine clinics. AB - The current wide choice of microscopes and the use of the microscope as a diagnostic tool is discussed. The formation of images and the aberrations which occur with lenses and the ways in which these are corrected are described. The functions of eye pieces and illuminating systems are presented. The requirements for microscopes in every day use, research microscopes and portable microscopes are described, and suggestions made as to how these requirements may be fulfilled. Brief comments on the care and maintenance of microscopes are made, and a list of manufacturers and suppliers appended. PMID- 2196219 TI - Roles of adhesion molecules in T-cell recognition: fundamental similarities between four integrins on resting human T cells (LFA-1, VLA-4, VLA-5, VLA-6) in expression, binding, and costimulation. AB - This review summarizes our recent work on expression and function of 4 integrins on resting human CD4+ T cells. Three themes are highlighted: multiplicity of molecular pathways of adhesion, regulation of adhesion, and costimulation by adhesion molecules. Four distinct receptor/ligand interactions have been elucidated: LFA-1/ICAM-1, VLA-5/fibronection, VLA-4/fibronectin, and VLA 6/laminin. Our studies indicate fundamental similarities in function and regulation of these four receptor/ligand interactions: 1) acute activation of the T cell (by CD3/TCR crosslinking or by PMA) induces rapid but transient integrin binding function; and 2) higher expression of each integrin on memory T cells compared to naive T cells results in greater binding of memory cells to each ligand. The identification of T-cell integrins (VLA-4, VLA-5, VLA-6) which interact with ECM components directs attention to the potential importance of T cell interactions with ECM components which either may be immobilized in ECM or which may act as molecular bridges between cells. The existence of multiple adhesion pathways, of multiple ligands for a single receptor (such as LFA-1/ICAM 1 and LFA-1/ICAM-2), multiple receptors for a single ligand (such as VLA-4/FN and VLA-5/FN), and regulation of ligand expression (ICAM-1) provides opportunities for co-operativity, rebundancy and diversity which the T cell utilizes to exquisitely regulate its adhesive interactions. The thesis that adhesion molecules can be multifunctional receptors that also influence signalling is demonstrated by our findings that each of these integrin receptor/ligand interactions is capable of providing a potent costimulatory signal to CD3 mediated T-cell activation. The importance of interactions of T-cell integrins with their cell surface and ECM ligands is discussed with respect to T-cell migration, differentiation and recognition. Analysis of the precise mechanisms by which T cells regulate and exploit these multiple receptor/ligand interactions and the resulting functional consequences of those interactions will be exciting areas of future research. PMID- 2196220 TI - Structure and function of leukocyte integrins. PMID- 2196221 TI - Membrane proteins involved in phagocyte adherence to endothelium. PMID- 2196222 TI - Potassium induced insulin release from isolated islet of Langerhans of albino rats. AB - The secretory effect of Potassium (K+) on endocrine pancreas was studied using collagenase digested isolated islets of Langerhans. Isolated islets of Langerhans incubated in KRB containing 5 15, 30 and 45 mM, quantity of additional K ions caused the release of insulin from beta-cells (significant release of insulin, P less than 0.01, at 15, 30 and 45 mM K+ in presence of 2.8 mM glucose and at 30 mM K in presence of 16.7 mM glucose). But lysosomal AP and CB enzymes did not record proportionate change. Thus a definite stimulation in the release of insulin without significant change in AP and CB were seen. PMID- 2196223 TI - Hepatic superoxide dismutase, catalase and lipid peroxidation products in Mastomys natalensis infected with Plasmodium berghei. AB - P. berghei infection in M. natalensis caused a significant reduction in the hepatic SOD and catalase activities. Cu-Zn SOD was more susceptible to infection than Mn SOD. The inhibition of enzyme activities was associated with marked increase in the levels of lipid peroxides, lipid hydroperoxides and conjugated dienes in infected M. natalensis. The alterations in the hepatic SOD, catalase and lipid peroxides are related with the severity of infection. PMID- 2196224 TI - Monoclonal antibodies defining the skin-selective alloantigens, Skn. PMID- 2196225 TI - Factors which affect growth of amniotic fluid cells. AB - In a study on various factors which are known to influence the growth of amniotic fluid cells for successful cytogenetic analysis in 89 samples, amniotic fluid volume greater than 10 ml enhanced the chance of success (P = 0.0003). The presence of red blood cells reduced the success rate although this was not statistically significant. Among the techniques which proved successful were the use of closed culture method (plastic flasks in which 5% CO2 is blown), and the addition of Ultroser G, which enhances the adhesion and growth of amniotic fluid cells. PMID- 2196226 TI - Microbial "superantigens". PMID- 2196227 TI - Mouse model for colonization and disease caused by enterohemorrhagic Escherichia coli O157:H7. AB - Enterohemorrhagic Escherichia coli O157:H7 isolates produce Shiga-like toxins and carry a 60-megadalton plasmid which encodes an adhesin for Henle 407 intestinal cells. A streptomycin-treated mouse model was used to compare the intestinal colonizing capacity of E. coli O157:H7 strain 933 with that of its 60-megadalton plasmid-cured derivative, strain 933cu. When fed individually to mice, both 933 and 933cu maintained a stable number of organisms per gram of feces, and the greatest numbers of 933 or 933cu were isolated from cecal and proximal colonic epithelial cells. When 933 and 933cu were simultaneously fed to mice, 933cu was unable to maintain a stable level of colonization in about two-thirds of the mice tested. However, in one-third of the mice, the number of 933cu in feces began to increase rapidly until a stable level of co-colonization with 933 was attained. The isolate from these mice, 933cu-rev, was excreted in high numbers when fed alone to mice and was found on epithelial cells throughout the entire large bowel and distal small intestine. Moreover, 933cu-rev grew in mucus from all segments of the intestine and at higher levels than strain 933 or 933cu. Only mice fed strain 933cu-rev died. Histopathological studies confirmed that mice fed 933cu rev died from bilateral renal cortical tubular necrosis consistent with toxic insult, perhaps due to Shiga-like toxins. The virulence of 933cu-rev may reflect its ability to grow well in mucus and colonize the small as well as large bowel. PMID- 2196228 TI - Characterization and identification of early proteins in Chlamydia trachomatis serovar L2 by two-dimensional gel electrophoresis. AB - The synthesis of early proteins from Chlamydia trachomatis serovar L2 was analyzed by two-dimensional gel electrophoresis. By pulse-label experiments, the synthesis of seven proteins was observed at 2 to 8 h postinfection before the major outer membrane protein was detected at 8 to 10 h after infection. The early proteins were synthesized throughout the 30-h period investigated, but the synthesis of three proteins of 75, 62, and 45 kilodaltons decreased from 26 to 30 h postinfection. Pulse-chase analysis showed that the signals from the same three proteins declined 26 to 30 h after infection. Three of the early proteins were identified as the S1 ribosomal protein, the GroEL-like protein, and DnaK-like protein, respectively. PMID- 2196229 TI - Partial characterization of an interleukin-1-like factor in human gingival crevicular fluid from patients with chronic inflammatory periodontal disease. AB - A significant level of interleukin-1-(IL-1)-like activity was detected in gingival crevicular fluid obtained from sites in patients with chronic inflammatory periodontal disease, confirming a previous report of IL-1-like activity detected in human gingival crevicular fluid from patients with chronic inflammatory periodontitis (J. A. Charon, T. A. Luger, S. E. Mergenhagen, and J. J. Oppenheim, Infect. Immun. 38:1190-1195, 1982). In the present study, we sought to investigate whether this IL-1-like activity belonged to IL-1 alpha or IL-1 beta and to characterize some of the biochemical properties of this factor. Polyclonal antibodies against recombinant human IL-1 alpha or IL-1 beta (rIL-1 alpha or rIL-1 beta) have been used for serological comparison of the IL-1-like factor. IL-1-like activity was completely neutralized by anti-human rIL-1 alpha antiserum, but not by anti-human rIL-1 beta antiserum. On gel filtration with a high-pressure liquid chromatographic Superose 12 column, IL-1-like activity was separated into two peaks, one with a molecular weight of about 43,000 and the other with a molecular weight of less than 17,000. The majority of the IL-1-like factor with a low molecular weight in human gingival crevicular fluid migrated at a molecular weight of about 17,000 under the reducing conditions of sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The specificity of the IL-1 like factor was further confirmed by an immunochemical method (Western blotting [immunoblotting]) by using anti-human rIL-1 alpha monoclonal antibodies. On isoelectric chromatography with a high-pressure liquid chromatographic Mono P column, the pI of this IL-1-like factor was between pH 4.9 and 5.2. These results suggest that the IL-1-like factor in human gingival crevicular fluid from diseased sites in patients with chronic inflammatory periodontitis consists predominantly of IL-1 alpha. PMID- 2196230 TI - Comparison of candidacidal and candidastatic activities of human neutrophils. AB - Disruption of neutrophils causes the release of a cytoplasmic protein which can inhibit the growth of Candida albicans without killing the organisms. The present study was undertaken with a combined system in which candidacidal and candidastatic activities of human neutrophils could be compared. In this system it was found that disruption of either half or all of the neutrophils in the samples markedly improved the ability of the cells to handle an inoculum of Candida yeast cells over a 48-h period, even though the disrupted cells had primarily candidastatic activity, with very little candidacidal activity. PMID- 2196231 TI - The Chlamydia trachomatis hyp operon is homologous to the groE stress response operon of Escherichia coli. AB - The Chlamydia trachomatis serovar A hyp operon was cloned, sequenced, and expressed in Escherichia coli. Two cotranscribed open reading frames, hypA and hypB, encoded polypeptides of 17 and 57 kilodaltons, respectively. The deduced amino acid sequences of serovar A HypA and HypB proteins were (respectively) 85 and 94% identical with HypA and HypB proteins of Chlamydia psittaci GPIC, and HypB was greater than 50% identical to 60-kilodalton stress response proteins from other procaryotes and eucaryotes. The sequence should be useful in defining the antigenic structure of the Chlamydia trachomatis HypB protein, a necessary step toward understanding the relationship between the immune response to this protein and the pathogenesis of human chlamydial diseases. PMID- 2196232 TI - Cutaneous tuberculosis. Current concepts. PMID- 2196233 TI - Risks of infection to dermatologists, cosmetic workers, and the public. PMID- 2196234 TI - Dermatitis herpetiformis--what is it? PMID- 2196235 TI - Oral manifestations of cutaneous T cell lymphoma. AB - Oral manifestations of cutaneous T cell lymphoma (CTCL) have received little attention in the dermatologic literature. The authors report two patients with lingual lesions. The histologic features are similar to those of the glabrous skin. A review of the 22 previously reported cases indicate a shortened survival. A retrospective review of 82 patients with CTCL treated at the authors' medical center identified only three with oral involvement. Radiation therapy offers effective palliation for these lesions. PMID- 2196236 TI - Carl L. Sigmund (1810-1883). The world's first professor of syphilis. PMID- 2196237 TI - Recent advances in dermatology and medicine (1989). PMID- 2196238 TI - Immunoglobulin G, complement factor C3 and lymphocytes in proliferative intraocular disorders. AB - This study examines a possible immunological contribution to the development of proliferative intraocular disorders (PID) with traction retinal detachment. We analysed 24 periretinal membranes and 35 vitreous aspirates from patients with idiopathic proliferative vitreoretinopathy (PVR), traumatic PVR, and proliferative diabetic retinopathy (PDR). Lymphocytes and complement factor C3 deposits could not be detected in any of the membrane specimens. IgG was present in all but one of the PVR membranes but in less than half of the PDR specimens and there to a lesser extent. The IgG immunoreactivity was not collocalized with macrophages but instead located to the extracellular matrix. The intravitreal levels of IgG (ELISA) and protein were elevated in PID but the range of these biochemical changes was so wide that there were no significant differences of the IgG levels between the single types of PID. Using electrophoresis and Western blotting, C3 was detected in normal and pathologic vitreous but smaller C3 fragments indicative of C3 breakdown were only found in PID. PMID- 2196239 TI - Is nimodipine useful in migraine prophylaxis? Further considerations. AB - Nimodipine is one of the most discussed calcium antagonists used in cerebrovascular diseases and, recently, in migraine prophylaxis. Its specificity in preventing cerebral arterial constriction has been invoked to explain nimodipine's efficacy in migraine. The discovery of neuronal receptors specific for dihydropyridines, however, favours a mechanism of action for nimodipine that is not exclusively vascular. This is in accordance with a view of migraine pathogenesis which implicates a primary neuronal event as the basis of the vascular changes observed in migraine patients. PMID- 2196240 TI - A controlled evaluation of the addition of cognitive therapy to a home-based biofeedback and relaxation treatment of vascular headache. AB - Seventy-six patients with vascular (migraine or mixed migraine and tension) headache (HA) participated in a controlled evaluation of a minimal-therapist contact, largely home-based, treatment program which combined relaxation (R) training with thermal biofeedback (TBF). One group received TBF + R administered in 3 office visit over 8 weeks, supplemented by audio tapes and manuals. A second group received the TBF + R plus instruction in cognitive stress coping techniques, all of which was administered in 5 office visits over 8 weeks. A third group monitored headache activity for 8 weeks. Evaluations, based on 4 weeks of HA diary at pre-treatment and after treatment, revealed significantly greater reductions in HA activity and medication consumption for both treated groups than the HA monitoring controls who did not change. Significantly more of the treated patients had clinically significant reductions in HA activity than the controls. The two treated groups did not differ on any measure. PMID- 2196241 TI - Biokinetics of 237Pu citrate and nitrate in the rat: implications for Pu studies in man. AB - Plutonium-237 decays mainly by electron capture with a half-life of 45 d. Alpha particles are emitted in only 5 x 10(-3)% of its disintegrations. This nuclide can now be produced with relatively small amounts of alpha-emitting contaminants so that, in principle, 237Pu can be used for studies of Pu biokinetics in man. However, because of its high specific activity, there was some doubt that its metabolism would be the same as that of the alpha- and beta-emitting isotopes of Pu normally encountered in the nuclear industry. In this study, the biokinetics of nearly "pure," high specific activity 237Pu are compared with those of lower specific activity, "impure" 237Pu containing significant amounts of alpha emitting Pu, following administration to rats by intravenous injection as the citrate. Both the distribution and excretion of the "pure" and "impure" 237Pu used in the two studies were similar and also in good agreement with the results of previously reported studies using 239Pu and 241Pu citrate, thus validating the use of 237Pu for studies of Pu metabolism in man. Data on the biokinetics of 237Pu nitrate are also included. PMID- 2196242 TI - Cardiac care. Signal-averaged electrocardiograms. AB - The signal-averaged electrocardiogram (ECG) is a simple, noninvasive test used to predict which patients may be prone to sudden cardiac death because of ventricular tachycardia. Signal averaging allows detection of low-amplitude waveforms in the ECG that are normally masked by noise. The averaging process is done by a computerized ECG machine. The results of abnormal signal-averaged ECGs can be used to predict ventricular tachycardia in patients after a myocardial infarction, with syncope, and after subendocardial resections. Application of the signal-averaged ECG in many other types of patients is currently being studied. The use of this diagnostic tool is rapidly increasing. Cardiac nurses should be aware of the methods and current research results of signal averaging. PMID- 2196243 TI - "Auto-PEEP": incidence, magnitude, and contributing factors. AB - In patients receiving mechanical ventilation there occasionally occurs an unintentional positive end-expiratory pressure, known as auto-PEEP, a phenomenon that can easily go undetected. Potential adverse effects of auto-PEEP include misleading hemodynamic information, cardiopulmonary morbidity, or both. Our study was designed to evaluate the incidence of auto-PEEP, its magnitude, and factors influencing it in a university hospital. Every patient receiving ventilation was evaluated for controlled ventilation and auto-PEEP in medical and surgical intensive care units during a 3-month period. Expiration was stopped at the instant that the next inspiration would have been delivered. At this moment, when the pressures in the lung and the ventilator circuit had equilibrated, the level of auto-PEEP was systematically measured. Of 57 patients undergoing controlled mechanical ventilation, 27 (47%) had 1 to 6 cm H2O of auto-PEEP. The incidence of auto-PEEP increased significantly when the minute ventilation exceeded 18.4 L/min, the respiratory rate was higher than 27 breaths/min, or the set PEEP was greater than or equal to 10 cm H2O. Therefore, auto-PEEP is the result of several ventilator-related factors. Because auto-PEEP occurred in 47% of the patients in the study, routine monitoring for auto-PEEP in patients receiving controlled ventilation is recommended. Further studies of auto-PEEP and its clinical impact are warranted. PMID- 2196244 TI - Wound repair and the potential use of growth factors. AB - Failure of wounds to heal increases the physical and financial burden of hospitalization and increases the work load for health care professionals. Although careful attention to nutrition (including adequate replacement of vitamins and trace mineral elements), tissue perfusion and oxygenation, and wound dressing and sanitation promote more rapid and complete healing, some wounds respond only slowly or not at all to these conventional treatment modalities. A group of polypeptide growth factors, including epidermal growth factor, platelet derived growth factor, transforming growth factor beta, and basic fibroblast growth factor, have been found to promote or hasten healing in animal models. This technology is now moving into the clinical arena where its potential for human healing must be evaluated. PMID- 2196245 TI - Reassessing intensive care for patients with the acquired immunodeficiency syndrome. AB - The number of patients with the acquired immunodeficiency syndrome (AIDS) admitted to hospitals is increasing dramatically. Treatments such as zidovudine, aerosolized pentamidine, and nutritional support are being administered to subacutely ill patients with increasing effectiveness. The number of patients with AIDS treated in intensive care units, on the other hand, has been decreasing progressively, perhaps as a result of a mortality rate close to 90%. However, because recent data demonstrate (1) a lower mortality rate in patients with AIDS who receive mechanical ventilation and (2) the ability to reverse the wasting syndrome in selected groups, we propose a reassessment of the criteria for intensive care unit admission of patients with AIDS. PMID- 2196246 TI - What are the needs of families of critically ill patients? A review of the literature since 1976. AB - The research conducted on families' needs in critical care was reviewed to summarize the findings for practice and recommend future directions for research on this topic. A literature search yielded eight articles in which replicable primary research on the needs of families of critically ill patients was reported. These reports, although individually limited by small sample size, presented similar findings. Families rated information needs most important, followed by needs for reassurance and convenience. Strategies to enhance information to families, such as written information, daily contact with physician or nurse or both, and establishing a nurse contact person for families and a family contact person who can be called about changes in patient status, are presented. Recommendations for future research include the study of elderly and male family members and tests of interventions aimed at meeting families' needs. PMID- 2196247 TI - Changing concepts in the management of congestive heart failure. PMID- 2196248 TI - Critique of "Stereotactic radiosurgery for intracranial arteriovenous malformations using a standard linear accelerator". PMID- 2196249 TI - Causes of degenerative joint disease (osteoarthrosis) and dyschondroplasia (osteochondrosis) in pigs. PMID- 2196250 TI - Clinical pharmacology of rifampin. PMID- 2196251 TI - Following in father's footsteps. PMID- 2196252 TI - Tick parasitism and antibodies to Borrelia burgdorferi in cats. AB - Ticks were removed from naturally infested cats, and serum samples from these cats were tested for antibodies to Borrelia burgdorferi. Twenty-two of 93 cats (23.7%) had one or more motile stages of Ixodes dammini attached. Of 2 larvae and 20 nymphs removed from cats, 1 larva and 2 nymphs were infected with B burgdorferi. Spirochetes were not found in tissues of 13 female and 4 male ticks. Ten of 71 serum samples analyzed by indirect fluorescent antibody staining or ELISA contained antibodies to this spirochete. Maximal antibody titers were 1:256 and 1:2,560, respectively. At titers greater than or equal to 1:160 in ELISA, seropositivity ranged from 8.8% (n = 34 sera tested from 34 cats) in May through July to 33.3% (n = 12 cats tested) during February through April. In clinical studies of 30 cats, there were nearly equal percentages of seropositive cats with limb or joint disorders not accompanied by fever, anorexia, or fatigue (5 of 21 cats) and cats with these signs of illness but lacking lameness (2 of 9 cats.) PMID- 2196253 TI - The avian tubercle bacillus and its relatives. PMID- 2196255 TI - Inactivation of Legionella pneumophila by monochloramine. AB - Chloramination which is used in South Australia to control the growth of Naegleria fowleri, was investigated to see if it would also control that of Legionella pneumophila. It was found that L. pneumophila was more sensitive than Escherichia coli to monochloramine. At 1.0 mg/l, a 99% kill of L. pneumophila was achieved in 15 min compared with 37 min for a 99% kill of E. coli. Combined with the stability of monochloramine, even at elevated temperatures, the results suggest that this disinfectant would control the growth of L. pneumophila in water distribution systems. PMID- 2196254 TI - Differentiation of three serovars of Malassezia furfur. AB - Malassezia furfur strains were isolated from the clinically normal skin of 10 volunteers by swabbing four different sites (forehead, ear, back and chest). The strains could be divided into three basic groups on the basis of cultural characteristics. Both unabsorbed and absorbed specific rabbit antisera were prepared against nine of the strains, and both species and group specific antigens could be demonstrated. Serologically, three group specific surface antigens could be identified which corresponded to the three groups identifiable on cultural characteristics. The relevance of these findings to previous in vitro results is discussed. PMID- 2196256 TI - Physiological variants of Saccharomyces cerevisiae and Kloeckera apiculata from palm wine and cashew juice. AB - Physiological variants of Saccharomyces cerevisiae and Kloeckera apiculata have been identified in oil palm wine and cashew juice from Nigeria. Genomic DNA from the four S. cerevisiae variants had a % G + C of 36-41% while that of K. apiculata was 32.2%. Fermentation of cashew juice produced wine of alcoholic contents of 10% with S. cerevisiae, 8% with K. apiculata and 9.3% with both yeasts simultaneously. PMID- 2196257 TI - Survival of Legionella pneumophila within cysts of Acanthamoeba polyphaga following chlorine exposure. AB - The association between Legionella pneumophila and the free-living amoeba Acanthamoeba polyphaga was studied. Intracellular growth of L. pneumophila within amoebic trophozoite was confirmed by kinetic growth experiments, light and electron microscopy. Cysts produced from infected trophozoites were found to protect the legionellas from at least 50 mg/l free chlorine. The ability of L. pneumophila to survive within the cysts of A. polyphaga is suggested as a possible mechanism by which the organism evades disinfection and spreads to colonize new environments. PMID- 2196258 TI - The influence of magnesium on ofloxacin activity against different growth phases of Escherichia coli. PMID- 2196259 TI - Potentiation of aminoglycoside inhibition and reduction of capsular polysaccharide production in Klebsiella pneumoniae by sodium salicylate. AB - This study determined the effects of sodium salicylate combined with several aminoglycoside antibiotics on the growth and capsular polysaccharide (CPS) production of Klebsiella pneumoniae. Salicylate significantly enhanced in inhibitory effect of all aminoglycoside antibiotics against all bacterial strains tested. The production of CPS was decreased by 62-86% when 2.5 mM salicylate was used. Amikacin combined with salicylate reduced CPS only slightly more than salicylate alone. The chelating agents, ethylenediamine tetra-acetic acid and ethylene bis tetraacetic acid, which have similar CPS-reducing properties, did not enhance the inhibitory effect of amikacin. Noncapsular variants of strains of K. pneumoniae were as susceptible to amikacin as the fully encapsulated strains, with or without salicylate present. Therefore, the combination of salicylate and the aminoglycosides acted synergistically to inhibit K. pneumoniae growth, but the increase in antibiotic sensitivity with salicylate was not a result of a reduction in CPS production. The use of salicylate in maximum therapeutic doses may enhance the activity of aminoglycosides sufficiently to allow the dose of aminoglycoside to be reduced when infections due to K. pneumoniae are treated. PMID- 2196260 TI - Cefepime concentrations in bronchial mucosa and serum following a single 2 gram intravenous dose. AB - The concentrations of cefepime in bronchial mucosa were measured after intravenous administration of a single 2 g dose in 20 patients undergoing diagnostic fibreoptic bronchoscopy. These concentrations were compared with simultaneous serum concentrations. The mean bronchial mucosal concentration was 24.1 mg/kg (s.d. 17.8 mg/kg) and the mean serum concentration was 40.4 mg/l (s.d. 28.1 mg/l). The mean percentage penetration was 59.8% (s.d. 12.5%). We conclude that a twice daily dosing of cefepime would be adequate for most respiratory infections although an 8-hourly dose may be necessary in pseudomonal infections. PMID- 2196261 TI - Comparative efficacy and tolerance of erythromycin and josamycin in the prevention of bacteraemia following dental extraction. AB - The tolerance and pharmacokinetics of erythromycin stearate and josamycin base were compared in healthy dental students. The efficacy and tolerance of the two antibiotics were compared in the prevention of bacteraemia following dental extraction. Erythromycin achieved higher serum levels at the time of extraction in dental patients than did josamycin. Erythromycin was rapidly and better absorbed than josamycin in the student volunteers, but josamycin caused less gastrointestinal side effects than erythromycin. Both antibiotics were only marginally more effective than placebo in preventing bacteraemia following dental extraction. PMID- 2196262 TI - A review of pulmonary function testing in children. PMID- 2196263 TI - The role of colony-stimulating factors in acute leukemia. AB - This article summarises the effects of colony-stimulating factors and related molecules on leukemia blasts by focussing on autocrine and paracrine growth control. This information may lead to a better understanding of the pathobiology of this highly malignant disorder, and may have therapeutic implications. PMID- 2196264 TI - c-myc overexpression is a tumor-specific phenomenon in a subset of human colorectal carcinomas. AB - The transcriptional activity of the c-myc proto-oncogene was examined in 25 primary human colorectal carcinomas and their corresponding normal mucosae. The purpose was to determine whether the elevated levels of c-myc expression, frequently detected in this type of tumor, might be the consequence of alterations in the cell growth rate or the effect of a real transcriptional deregulation of the gene. In about 44% of the tumors the elevated c-myc expression was consequent to the enhanced growth rate of the neoplastic tissue, as estimated by the expression of the S-phase-specific histone H3 gene. In the other 56%, c-myc overexpression did not entirely depend on the proliferative activity of the neoplastic population. In this latter group, c-myc deregulation did not reside in structural modifications of the putative regulatory regions of the gene. Therefore, c-myc overexpression, at least in a subset of colorectal cancer, seems to be consequent to alterations in transregulative phenomena exerted on the c-myc gene by other genetic loci. PMID- 2196265 TI - Phase II study of carboplatin and cytosine arabinoside in patients with disseminated malignant melanoma. AB - Twenty-one patients with disseminated malignant melanoma were treated with a combination of carboplatin and cytosine arabinoside. Two complete and three partial remissions occurred. No complete cross-resistance was found with a regimen containing 5-(dimethyltriazeno)imidazole-4-carboxamide (DTIC) in two patients. It is suggested that this regimen might be studied further as a second line treatment for patients who fail on DTIC-containing treatment. PMID- 2196266 TI - Ischemia-reperfusion syndrome of skeletal muscle. PMID- 2196267 TI - Noninvasive imaging of the superficial femoral artery using ultrasound Duplex scanning. AB - A total of 56 lower extremities in 28 patients were evaluated by both conventional arteriography and ultrasound duplex scanning. Overall sensitivity for duplex scanning compared to arteriography in detecting stenotic or occlusive disease was 91%, specificity was 94%, positive predictive value 85% and negative predictive value 97%. Results for Duplex scanning were better in the proximal and middle segment compared to the distal third of the superficial femoral artery. The sensitivity of segmental lower extremity pressures and pulse volume recordings for predicting proximal superficial femoral artery disease compared to arteriography was 82%; specificity was 79% and accuracy 80%, all inferior to that of Duplex scanning. Duplex scanning is a promising technique suitable for noninvasive assessment of patients presenting with suspected superficial femoral artery disease. It should readily identify candidates for percutaneous interventional techniques in which a patent segment of proximal superficial femoral artery is required for access. It will also be useful in follow-up studies of patency of the superficial femoral artery following interventional procedures such as balloon dilatation and laser angioplasty. PMID- 2196268 TI - Inferior vena cava occlusion secondary to aortic aneurysm. AB - A case of inferior vena caval thrombosis secondary to aortic aneurysm is presented with management guidelines. CT scanning, as well as conventional venography and arteriography, is very useful in understanding this process preoperatively. Intraoperative management should prevent pulmonary embolism and should anticipate the possibility of blood loss in excess of that which usually occurs with an uncomplicated aneurysm repair. Detailed review of the literature reveals this is a rare complication of aneurysm disease and a potentially lethal one. PMID- 2196270 TI - The peripheral nervous system--central nervous system regeneration dichotomy: a role for glial cell transplantation. PMID- 2196269 TI - Bilateral superficial femoral giant cell arteritis. AB - Giant cell arteritis is a rare, poorly understood, and often misdiagnosed entity. A case is reported of giant cell arteritis in a 30-year-old white male who developed severe bilateral peripheral claudication affecting both legs. The erythrocyte sedimentation rate (ESR) was markedly elevated. The diagnosis of vasculitis was established by histology postoperatively following exploration of both superficial femoral arteries and the placement of a reversed saphenous vein bypass graft to the right leg. Biopsy of the temporal artery revealed no pathology. The patient has been completely asymptomatic postoperatively and has resumed all previous normal activities. This condition has persisted in spite of a failed graft determined by an arteriogram performed 3 months after surgery. He has been treated with steroids continuously since the procedure. PMID- 2196271 TI - The differentiation process of intestinal epithelial cells is associated with the appearance of statin, a non-proliferation-specific nuclear protein. AB - The expression of statin, a 57,000 Mr nuclear protein specifically present in non proliferating cultured fibroblasts, was studied in vivo in the differentiating epithelial cells of the rat intestine. Using immunofluorescence microscopy we found that undifferentiated, proliferating crypt enterocytes are statin negative, whereas the differentiated non-proliferating villus enterocytes are statin positive. The epithelial cells of the intestine were isolated according to different stages of differentiation and the expression of statin was studied biochemically by immunoblotting assays. The prominent band (57,000 Mr) was present in abundance in villus cell fractions but undetectable in crypt cell fractions. These findings were also confirmed by immunofluorescence microscopy on individual intestinal epithelial cells of the different isolated fractions. The results presented here, which are similar to observations made in cell cultures, suggest that statin is a unique protein associated with the non-proliferative state of differentiated cells in tissue. PMID- 2196272 TI - The circadian bioluminescence rhythm of Gonyaulax is related to daily variations in the number of light-emitting organelles. AB - The number of scintillons, which are cellular organelles responsible for light emission in the marine alga Gonyaulax, were counted by both immunofluorescence and electron microscopic methods and found to vary tenfold between subjective day and subjective night. The number of scintillons peaks during the subjective night, as does stimulated bioluminescence (flashing). Furthermore, the number drops sharply at the time of the maximal spontaneous bioluminescence (glow), which occurs at the end of the night phase, suggesting that the breakdown of scintillons may be responsible for this mode of emission. PMID- 2196273 TI - Production of avian antibodies to three potyviruses in coturnix quail. AB - Avian antibodies against three potyviruses were produced in a small bird, coturnix quail (Coturnix coturnix japonica Temminck et Schlegel), with 15-60 micrograms of purified virus preparations. Intramuscular injections of immunogen with Freund's incomplete or complete adjuvant into the birds did not result in higher titer of antibody compared to that of control birds given intravenous injections. Quail egg yolk antibody was as useful as hen antibody for indirect ELISA and allowed virus to be detected in purified preparation (10-50 ng/ml) and in crude extracts (10(-6)-10(-7) dilution). The advantages of using quail to produce avian antibodies are discussed. PMID- 2196274 TI - Automated electrokinetic analysis; description and application in virology and cell biology. AB - The electrophoretic mobility (EPM) of selected macromolecules in solution was shown to be accurately determined using an automated electrokinetic analyzer, the PenKem S3000. In addition, the S3000 was used to monitor the effects of T4 phage infection on the EPM of Escherichia coli B. EPM, expressed as the ratio of velocity in microns/sec to field strength in V/cm, was measured for calf thymus DNA, for pneumococcal capsular polysaccharide serotype 3 (PCP-3), and for bovine serum albumin (BSA) unbound in solution; values of -3.05, -2.736 and -1.176, respectively, were obtained. The EPM of these macromolecules remained the same when they were bound to latex beads. The S3000 may therefore be suitable for measurement of the EPM of unbound macromolecules. The EPM of T4 phage in solution was measured to be -1.203. However, both the zwitterionic latex-bound T4 phage as well as T4 phage disrupted by ultrasonication exhibited an EPM of approximately 2.50, suggesting to us that binding to zwitterionic latex may cause release of phage DNA. The notion that phage DNA is responsible for the increased negative charge was supported by the observation that the EPM of E. coli B increased to the level of free DNA within 5 min when E. coli B (the host cell for phage T4) had been exposed to 10 phage particles per cell. Electronmicrographs of phage infected E. coli B cells showed numerous strands of free DNA at the bacterial surface. It is concluded that the S3000 not only measures the EPM of macromolecules in solution but that the instrument can be used also to monitor the behavior of the host cell surface in response to attachment of viral particles. PMID- 2196275 TI - More support for the use of HIV combination assays. PMID- 2196276 TI - Clinical review 10: An endocrinologic approach to the patient with hirsutism. PMID- 2196277 TI - A potential primate model for bone loss resulting from medical oophorectomy or menopause. AB - This study examined the potential use of the GnRH agonist-treated female monkey as a model for bone loss after medical oophorectomy or the onset of menopause in women. Three female rhesus monkeys (13-16 yr of age) were treated continuously for 10 months with 25 micrograms/day GnRH agonist using osmotic minipumps. All three animals exhibited normal menstrual cycles before treatment. Within 5 weeks of the beginning of GnRH agonist treatment, serum progesterone and estradiol concentrations had fallen to low values and did not rise significantly during the remaining treatment period. The decline in ovarian steroidogenesis was correlated with a reduction in bone mineral density (BMD; bone mineral content/bone width) of the caudal vertebrae and humerus. The reduction of BMD of the caudal vertebrae occurred gradually. The downward trend was evident during the first 3 treatment months, but did not fall significantly below pretreatment levels until 9 months of GnRN agonist treatment. The overall decline in BMD for the caudal vertebrae was approximately 14% after 9 months of GnRH agonist treatment. The measured decline in BMD of the humorous was 11%. Serum osteocalcin levels rose more than 10-fold above pretreatment values between 4 and 7 months of GnRH agonist treatment before declining to levels that approached pretreatment concentrations between 8 and 10 months of treatment. Menstrual cycles were reinitiated within 4 weeks after the termination of treatment, as shown by luteal phase increases in serum progesterone concentrations. BMD of the humerus and caudal vertebrae remained subnormal 2 months posttreatment, but by 5 months had recovered to near pretreatment values. These data suggest that ovarian hormone deprivation induced by GnRH agonist administration is associated with a decline in BMD in female monkeys, and that this animal model may be an excellent model for postmenopausal bone loss or bone reduction resulting from medical oophorectomy. The GnRH agonist treated monkey also has the potential to be developed as a model for type I postmenopausal osteoporosis. PMID- 2196278 TI - Identification of placental human growth hormone as the growth hormone-V gene expression product. AB - A GH variant of placental origin, placental GH, has recently been shown to replace pituitary GH in maternal serum during pregnancy. Besides, the GH variant (GH-V) gene has been demonstrated to be expressed in the placenta. The similarities between their known properties strongly suggest that the placental GH and the GH-V protein are the same molecular species. Here we provide final evidence that this is indeed the case by sequence analysis of both the 22K and 25K forms. Furthermore, the 25K form is shown to be glycosylated, while the 22K form is not. Both size variants of placental GH are, thus, likely to reflect the partial glycosylation of a unique peptidic chain. PMID- 2196279 TI - Two unrelated patients with familial hyperproinsulinemia due to a mutation substituting histidine for arginine at position 65 in the proinsulin molecule: identification of the mutation by direct sequencing of genomic deoxyribonucleic acid amplified by polymerase chain reaction. AB - Mutations in the insulin gene can impair the bioactivity of the insulin molecule. Previously, two classes of mutations have been identified: 1) those that impair posttranslational processing of proinsulin to insulin, and 2) those that alter the structure of the insulin molecule, thereby reducing the affinity of the molecule for the insulin receptor. We have investigated two apparently unrelated patients, both of which have mutations that inhibit the conversion of proinsulin to insulin. By directly sequencing genomic DNA amplified by polymerase chain reaction, we have demonstrated that both patients are heterozygous for the same point mutation converting codon 65 from an arginine (CGT) to a histidine (CAT) codon. Because Arg65 is one of the two dibasic amino acids at the site of proteolytic cleavage between the insulin A-chain and C-peptide, this mutation explains the impairment in the cleavage of proinsulin to insulin. Interestingly, the same His65 mutation has been identified in the insulin gene of a Japanese kindred with familial hyperproinsulinemia. Thus, this mutation has occurred in three apparently unrelated kindreds from two different racial groups. This observation is consistent with the hypothesis that the dinucleotide sequence CpG, the first two nucleotides in the arginine (CGT) codon, is a "hot spot" for mutations. PMID- 2196280 TI - H-ras protooncogene mutations in human thyroid neoplasms. AB - Structural alterations of protooncogene sequences may be involved in the pathogenesis of human neoplasms. We screened 54 thyroid tumors (36 benign and 18 malignant) for gene rearrangements of the protooncogenes c-myc, c-myb, c-fos, c erb-B1, c-erb-B2, c-erb-A, N-ras, K-ras, and H-ras. Only mutations of H-ras were observed. None of the 15 colloid adenomas examined had detectable H-ras rearrangements. Of the remaining tumors, we observed mutations of H-ras in 4 benign and 4 malignant neoplasms. Gene amplification was found in 5 tumors. An aggressive recurrent papillary carcinoma had a marked amplification of one of the H-ras alleles. The amplified allele was truncated, in that the 3' variable tandem repeat was not a part of the amplification unit, and contained a codon 12 point mutation leading to a valine for glycine substitution. We also observed the association of low copy gene amplification with a codon 12 valine for glycine mutation in a follicular adenoma. Two tumors contained H-ras EcoRI polymorphisms not present in the DNA of normal thyroid from the same individuals, and one follicular carcinoma showed loss of an H-ras allele. Ras protooncogenes may become transforming by quantitative mutations, leading to increased expression, or qualitative mechanisms, through activating point mutations. Both of these appear to coexist in thyroid neoplasms, and it may be that a combination of both mechanisms is capable of inducing a more complete spectrum of neoplastic phenotypes. PMID- 2196281 TI - Attenuated pulsatile release of prolactin in men with insulin-dependent diabetes mellitus. AB - Pulsatile and circadian patterns of PRL release were studied in 11 insulin dependent diabetic men by sampling blood every 10 min for 24 h and comparing the results to those obtained in 12 normal nondiabetic men. The diabetic men had a mean (+/- SE) 24-h serum PRL concentration of 5.5 +/- 0.42 micrograms/L, which was significantly lower than that in the nondiabetic men (9.3 +/- 0.86; P = 0.0008). Quantitative Cluster analysis of pulsatile PRL time series revealed a normal pulse frequency, but decreased maximal peak amplitude (6.6 +/- 0.5 vs. 11.8 +/- 1.1 micrograms/L; P = 0.0009), peak increment (2.6 +/- 0.24 vs. 4.0 +/- 0.3 micrograms/L; P = 0.009), peak area (126 +/- 15 vs. 192 +/- 19 micrograms/L.min; P = 0.03), and interpulse valley mean concentration (4.8 +/- 0.4 vs. 8.6 +/- 1.2 micrograms/L; P = 0.0007). PRL pulse incremental amplitude correlated significantly (r2 = 0.577; P = 0.007) and negatively with duration of disease. Fourier analysis disclosed a normal circadian rhythm of PRL release in diabetic men, with a mean circadian amplitude of 1.5 micrograms/L +/- 0.31, which peaked at 0201 h +/- 89 min (+/- SE). In summary, we have demonstrated significantly reduced mean 24-h serum PRL concentrations in men with poorly controlled insulin-dependent diabetes mellitus. The concomitant suppression of spontaneous PRL pulse amplitude, peak increment, and interpulse valley mean concentrations in the presence of normal pulse frequency is consistent with a reduced mass of PRL secreted per burst and/or accelerated metabolic clearance of PRL in men with type I diabetes mellitus. PMID- 2196282 TI - Helicobacter pylori (formerly Campylobacter pyloridis/pylori) 1986-1989: a review. PMID- 2196284 TI - Leukaemic phase of mantle zone lymphoma. PMID- 2196283 TI - Prevalence of chlamydial antibody in Malaysians. AB - A single antigen indirect immunofluorescence test was used to screen for chlamydial antibody among Malaysian infants, children, sexually active adults and prostitutes. Of 794 serum samples tested, 361 (45.5%) were positive. Seropositivity increased with age and sexual activity and ranged from 10 to 16% among children under 10 years old to 94.4% among prostitutes. Pregnant women and female adolescents showed a higher antibody prevalence than nonpregnant and older women. Six (13%) infants under 6 months of age were positive for chlamydial IgM. PMID- 2196285 TI - Distribution of phosphate-activated glutaminase in the human cerebral cortex. AB - Phosphate-activated glutaminase (PAG), which catalyses conversion of glutamine to glutamate, is a potential marker for glutamatergic, and possibly GABA, neurons in the central nervous system. A polyclonal antibody, raised in rabbits against rat brain PAG, was applied to postmortem human brain tissue to reveal the distribution of PAG in the cerebral cortex. PAG immunoreactivity was observed in pyramidal and non-pyramidal neurons but not in glial cells. In the neocortex, large to medium-sized pyramidal neurons in layers III and V were stained most intensely, while the majority of smaller pyramidal cells were labeled either lightly or moderately. Such modified pyramids as the giant Betz cells, the large pyramidal cells of Meynert, and the solitary cells of Ramon y Cajal were also stained intensely. Fusiform cells in layer VI showed moderate to intense labeling. A number of cortical non-pyramidal neurons of various sizes stained moderately to intensely. These included large basket cells which were identified by their characteristic morphology and size in primary cortical areas. Pyramidal cells in the hippocampal formation as well as basket cells of the stratum oriens stained moderately to intensely. Since pyramidal cells are believed to be glutamatergic and large basket cells GABAergic, these results suggest that PAG plays a role in generating not only transmitter glutamate, but also GABA precursor glutamate. PMID- 2196286 TI - Mycosis fungoides in children and adolescents. AB - The clinical and histologic findings in five young patients with mycosis fungoides are reviewed. The skin specimen from a 16-year-old boy had an infiltrate predominantly Leu-1+, Leu-4+, Leu-3a + 3b+, OKT6+, Leu-2a-, Leu-8-, and Leu-9-, and rearrangements were noted in T cell receptor gene (beta chain [constant region probe] and gamma chain [J region probe]); no rearrangements were found in a histologically normal lymph node or peripheral blood. The skin specimen from an 11-year-old girl contained predominantly Leu-4+ and Leu-9+ lymphoid cells. No T cell receptor gene rearrangements were found in the skin or in an involved lymph node. The variations in clinical, histologic, and immunopathologic features suggest that mycosis fungoides in young patients represents a heterogeneous subgroup of cutaneous T cell lymphoma. PMID- 2196287 TI - Subcorneal pustular dermatosis in dogs and in human beings: comparative aspects. AB - Subcorneal pustular dermatosis is a rare disorder in dogs and in human beings. A retrospective study of 13 cases of canine subcorneal pustular dermatosis indicates that many of the clinicopathologic features of this disease are similar in both species. In both the condition is characterized by a variably pruritic, sterile, pustular eruption that is resistant to antibiotics and glucocorticoids. The therapeutic response to dapsone is not uniformly successful in either species, and the disorder tends to be chronic and recurrent. PMID- 2196288 TI - Sunscreening agent intolerance: contact and photocontact sensitization and contact urticaria. AB - Reports in the literature of sensitization associated with many commonly used sunscreening agents including p-aminobenzoic acid (PABA), PABA derivatives, anthranilates, salicylates, cinnamates, benzophenones, and dibenzoylmethane derivatives are reviewed. Several of these case reports involved subjects with various photodermatoses, implicating enhanced sensitivity of the patient's skin to both light and chemicals. Despite the widespread use of sunscreens, the small number of published reports of contact and photocontact sensitization to these agents suggests that either such sensitization is less than commonly perceived or is underreported. Establishment of a registry for reporting adverse effects associated with sunscreening agents would help to characterize the incidence of sensitization. PMID- 2196289 TI - Mononuclear phagocytic and dendritic cell systems. AB - This review presents a classification scheme for disorders of the mononuclear phagocyte and dendritic cell systems. Previous classifications, based primarily on cytomorphology, are now obsolete. Electron microscopy, enzyme histochemistry, and, especially, immunocytochemistry have revealed the histiocyte identified by hematoxylin-and-eosin staining to be not one but several cell types. Currently, two broad groups of histiocytic cells are recognized, the monocyte-macrophage group and the dendritic cells. Dendritic cells are further subclassified as Langerhans cells, indeterminate cells, interdigitating cells, and dermal dendrocytes. Many disorders of the skin and other organs are characterized by proliferation of "histiocytic"-appearing cells. Some of these diseases clearly behave in a malignant fashion, whereas others follow a benign or variable course. At present, the proliferating cell type has been identified in only a few of these disorders by ultramicroscopy and cytochemical and immunocytochemical methods. Nevertheless, the pieces of the puzzle are beginning to fall into place. In general, those disorders that typically behave in a malignant fashion have been more extensively studied. The benign histiocytic disorders of children and adults are a heterogeneous group of diseases. Currently, some of these disorders are unclassified or classified with uncertainty. For example, how should severe histiocytosis with massive lymphadenopathy be classified? There is a proliferation of nonlymphoid mononuclear cells that are positive for S-100 protein and negative for CD1 and that exhibit lymphophagocytosis. Is this then a mononuclear phagocytic or dendritic cell disorder? Juvenile xanthogranuloma is a disorder of macrophages. Self-healing reticulohistiocytosis and solitary Langerhans cell histiocytoma are benign proliferative disorders of Langerhans cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196290 TI - Isolation of viable virus from a patient with atypical measles and rash in an inverse photodistribution. PMID- 2196291 TI - Superficial thrombophlebitis. I. Primary hypercoagulable states. AB - This review concentrates on those disorders in which superficial thrombophlebitis can be a significant or presenting clinical sign. Primary hypercoagulable states are those conditions associated with an increased risk of thrombosis caused by a specific measurable defect in the proteins of coagulation and/or fibrinolytic systems. These disorders are frequently inherited and include deficiencies of antithrombin III, heparin cofactor 2, protein C, protein S, abnormal fibrinolytic activity, dysfibrinogenemia, and Hageman trait. Patients with a lupus anticoagulant and anticardiolipin antibody syndrome with thrombotic episodes are also considered to have a primary hypercoagulable state. The physiology, pathophysiology, clinical characteristics, and treatment of primary hypercoagulable states are reviewed. PMID- 2196292 TI - Fatty filum terminale: assessment with MR imaging. AB - Five cases of fatty filum terminale were encountered in a retrospective analysis of 332 routine lumbosacral magnetic resonance studies. The T1-weighted and GRASS images were particularly useful in evaluating the filum. An irregularly thickened fatty filum, especially if associated with a low conus, is likely to be pathologic and responsible for a patient's symptoms and signs. PMID- 2196293 TI - Lipomatous uterine tumors: diagnosis by ultrasound, CT, and MR. AB - Lipomatous uterine tumors are rare benign neoplasms that can be difficult to differentiate from benign cystic ovarian teratomas. However, if a fat containing mass can be clearly identified to be of uterine origin, the diagnosis of a lipomatous uterine tumor can be made. We present two cases in which a lipomatous uterine tumor was suggested by ultrasound and confirmed by CT and magnetic resonance. PMID- 2196294 TI - Preoperative CT and MR imaging of ischiopagus twins. AB - Each case of conjoint twins is unique. Preoperative imaging is helpful to determine the feasibility of separation. Shared and separate organs can be delineated; and operative technique and problems anticipated. We performed ultrasonography, CT, magnetic resonance imaging, and arteriography preoperatively on ischiopagus conjoint twins. The single most helpful study was CT performed during a bolus intravenous contrast medium injection into one twin. Arteriography was also very helpful. The other studies were complementary but added little additional structural details. Sedation of conjoint twins is complicated yet crucial for optimal imaging studies. A combination of oral and intramuscular sedation was used and worked well for all of the studies. PMID- 2196295 TI - Neurinoma of the oculomotor nerve: CT and MR features. AB - The authors present a case of neurinoma of the oculomotor nerve without evidence of von Recklinghausen disease. The literature is reviewed and CT and magnetic resonance findings are discussed. PMID- 2196296 TI - Why pick on teeth? AB - In the evolution of oral hygiene practices, the toothpick is the progenitor device. Although modern variations are used interdentally, with the current emphasis on plaque control rather than gingival massage and stimulation, the toothpick has been largely superseded by floss, interproximal brushes, and other supplementary aids. The natural hard bristle toothbrush and vigorous scrub brushing popular a generation ago have been replaced by soft bristle nylon brushes and gentler, more defined brushing procedures for plaque removal in the crevicular areas. Quantitative studies support the superiority of the current techniques in maintaining periodontal health with less trauma to the oral tissues. PMID- 2196297 TI - The oral mucosal punch biopsy: indications and technique. AB - The indications for advantages and disadvantages of the punch biopsy technique in the diagnosis of oral mucosal disease are discussed. The punch biopsy is recommended for use by the general practitioner as a simple, fast, inexpensive, and safe procedure for the diagnosis of oral mucosal lesions. PMID- 2196299 TI - Using glass ionomers. Council on Dental Materials, Instruments, and Equipment. PMID- 2196298 TI - Physical medicine procedures affect temporomandibular disorders: a review. AB - This article reviews the literature on the effectiveness of physical medicine procedures for treatment of temporomandibular disorders (TMD). Brief descriptions of some commonly used dental appliances, and pharmacological and surgical treatment methods are provided. PMID- 2196300 TI - Peanut anaphylaxis. PMID- 2196301 TI - Evidence for cross-reactive allergens among basidiomycetes: immunoprint inhibition studies. AB - Allergenic cross-reactivity among six basidiomycete species (Calvatia cyathiformis, Coprinus quadrifidus, Psilocybe cubensis, Pleurotus ostreatus, Ganoderma meredithae, and Pisolithus tinctorius) was determined by immunoprint inhibition. Extensive cross-reactivity was demonstrated among Coprinus quadrifidus, Psilocybe cubensis, and Pleurotus ostreatus of the order Agaricales, and Calvatia cyathiformis of the order Lycoperdales. However, G. meredithae (order Aphyllophorales) and Pisolithus tinctorius (order Sclerodermatales) did not demonstrate significant cross-reactivity with the other basidiomycete species. Generally, the two most potent inhibitors were Psilocybe cubensis and Pleurotus ostreatus. Inhibitory dose-response curves of a major allergenic band (isoelectric point, 9.3) were obtained by densitometry. Significant cross reactivity was demonstrated for the 9.3 band among the species of the order Agaricales and with Calvatia cyathiformis. The most potent inhibitors were again Psilocybe cubensis and Pleurotus ostreatus. Thus, there is substantial allergenic cross-reactivity among the species of the order Agaricales tested and with Calvatia cyathiformis but not between these four species and G. meredithae or Pisolithus tinctorius. These studies support earlier RAST-inhibition observations of shared allergenic epitopes among basidiomycetes, especially epitopes within the Agaricales. The presence of shared epitopes suggests the possibility of devising a panel of skin test reagents representative of a large group of basidiomycetes. PMID- 2196302 TI - Human conjunctival mast cells: distribution of MCT and MCTC in vernal conjunctivitis and giant papillary conjunctivitis. AB - The distribution and concentration of human tryptase-positive, chymase-negative mast cells (MCTS) and tryptase-positive, chymase-positive mast cells (MCTCS) were examined in conjunctival biopsy specimens from subjects with active vernal conjunctivitis (VC; n = 7), giant papillary conjunctivitis (GPC; n = 6), and allergic conjunctivitis (AC; n = 5), and from asymptomatic soft-contact lens wearers (SCL; n = 6) and normal control individuals (n = 19). Carnoy's fixed tissue sections were stained by a double immunohistochemical method using a biotinylated mouse monoclonal antichymase antibody with immunoperoxidase, followed by an alkaline phosphatase-conjugated mouse monoclonal antitryptase antibody. Epithelial mast cells (MCs) were found in all VC specimens (96% MCTCs) and in three GPC specimens (100% MCTCS) but in none of the other groups. In the substantia propria, MCTCS were the predominant type of MC observed in all specimens, accounting for 95% of the total MCs in the normal control group and 100% of the total MCs in the subjects with GPC, AC, and SCL. No significant differences were found in the total MC concentration of the substantia propria among the normal control subjects (11,054 +/- 6327 MCs per cubic millimeter), subjects in the SCL group (13,168 +/- 4685 MCs per cubic millimeter), subjects with GPC (17,313 +/- 8500 MCs per cubic millimeter), and subjects with AC (15,380 +/- 5660 MCs per cubic millimeter). In subjects with VC, the percentage of MCTs (18% +/- 13%) and the total MC concentration (24,689 +/- 18,978 MCs per cubic millimeter) in the substantia propria were significantly increased as compared to the normal control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196304 TI - Occupational challenge studies with laboratory workers allergic to rats. AB - To relate airborne Rat N I concentrations to airway responses in allergic laboratory workers, we collected allergen on personal monitors while workers and control subjects were exposed in a rat vivarium for 1 hour. Allergen concentrations ranged from less than 1.5 to 310 ng/m3 and were significantly (p less than 0.001) higher during cage cleaning (19 to 310 ng/m3) than during quiet activity (less than 1.5 to 9.7 ng/m3). Among 12 rat-allergic volunteers, all had a nasal response during the exposure with an increase in nasal lavage histamine concentrations or TAME-esterase activity, but only five volunteers had a lower respiratory tract response (fall in FEV1 greater than 10%). Two of five allergic control subjects had a small change in nasal TAME-esterase activity, and none had a 10% fall in FEV1. A dose response was demonstrated between the allergen concentrations and the intensity of the nasal allergic response. This occupational challenge procedure thus was able to measure the nasal and lower respiratory tract response to airborne allergen exposure in a work environment. It can be used to define further the determinants of this response. PMID- 2196303 TI - Resistance and allergy to recombinant human insulin. AB - Insulin allergy and antibody-mediated resistance may complicate therapy with animal insulins. We describe a 53-year-old man manifesting both resistance and persistent systemic allergy despite treatment with recombinant human insulin. Insulin resistance and symptoms of allergy appeared in this patient several months after initiating therapy with mixed beef-pork insulin, as is often the case. Symptoms initially improved, but persisted, and then worsened again, despite continuous human insulin therapy. Total insulin-binding capacity by Scatchard analysis, high plasma insulin-binding capacity, and specific anti insulin antibody levels were consistent with an immunologic form of insulin resistance. Glucocorticoid therapy was required both to reduce allergic findings and to restore glycemic control. Although recently available human insulins may be less immunogenic than animal forms, immune responses to exogenous human insulin still may pose significant clinical problems. PMID- 2196305 TI - An exploratory use of the Symptoms Checklist-90 in a mixed geriatric study group. AB - There are currently no self-rating scales of general psychopathology in the older population. Such scales can be used to screen patients who may then be referred on for psychiatric assessment. The validity of the Symptoms Checklist-90 (SCL 90), a self-rating scale of general psychopathology widely used in the nongeriatric adult population, was explored in 44 older subjects. It was compared with the Sandoz Clinical Assessment Geriatric (SCAG) scale and a measure of functional disability, the London Psychogeriatric Rating Scale (LPRS). Caregivers to all subjects also rated the degree of difficulty experienced with their care on a four-point scale. Thirty of the subjects attended a geriatric day hospital, and the remaining 14 were waiting to go into long-term care facilities. Symptoms Checklist-90 was not significantly different between the two groups of subjects (day hospital and preinstitutional) after Bonferroni corrections, though SCAG scale and LPRS were (P less than .01 for both). Although SCL-90 was correlated significantly with the SCAG scale (r = .46), it was not significantly correlated with the LPRS. It showed good internal consistency but poor face validity and an inability to differentiate between levels of difficulty for the caregiver. It is concluded that the use of SCL-90 in older people may be limited because of the lack of sensitivity to functional disability and care difficulty. This nevertheless needs to be further explored, perhaps with some modification of the scale for older people. PMID- 2196306 TI - Pygmalion in the nursing home. The effects of caregiver expectations on patient outcomes. AB - Several characteristics of nursing home care can diminish rather than enhance the clinical status of older residents. In view of evidence from other settings that "interpersonal expectancy effects" can influence outcomes in a variety of relations, we conducted a randomized controlled trial to test the effects of caregiver expectations on the clinical status of nursing home residents. Within 2 weeks of admission, 63 older residents at six nursing homes were given a comprehensive assessment of cognitive, functional, and emotional status. Residents were then randomly assigned to a "high-expectancy" or "average expectancy" condition. Nurses and aides were told that, in comparison with other residents having similar problems, residents in the high-expectancy group were predicted to perform above average in their rehabilitation. The assessment was repeated 3 months later; information on the health and psychosocial status of residents was drawn from their medical records covering the same period. Aides reported having higher expectations for treatment group residents. When assessed by a blinded research assistant, residents in the high-expectancy group experienced greater relief of depressive symptoms but showed greater decrements in functional independence in comparison with control residents. Treatment group residents were admitted significantly less frequently to hospitals despite a comparable number of emergency ward visits, suggesting a lower incidence of severe illness despite comparable medical surveillance. There was also a trend toward improved performance in mental status testing among the high-expectancy residents compared with controls (P = .08). Additional research is needed to define further the magnitude and mechanisms of expectancy effects in relations between nursing home caregivers and residents. PMID- 2196307 TI - Acquired hemostatic abnormalities in the elderly. PMID- 2196308 TI - Resource-based relative value scale: a new payment system for practitioners under Medicare. AB - Congress has directed the Physician Payment Review Commission to evaluate ways that the Part B Medicare program may be changed to modify the way physicians are reimbursed and to slow down the growth of expenditures in the program. This survey article summarizes the work in the development of a resource-based relative value scale (RVS), discusses the major issues dealt with by the PPRC, the results of Congressional action, and the issues of concern for optometrists. PMID- 2196309 TI - Cardiac output effects of endothelin-1, -2 and -3 and sarafotoxin S6b in conscious rats. AB - Conscious, Long-Evans rats, chronically-instrumented for the direct measurement of intra-arterial and central venous pressures and ascending aortic blood flow (i.e. cardiac output), were given bolus, intravenous doses (4 and 40 pmol) of endothelin-1, -2, or -3 or sarafotoxin S6b in random order. The lower dose of endothelin-1 and -3 and sarafotoxin S6b caused a significant increase in cardiac output. The higher bolus dose of the same three peptides caused initial hypotension and increases in cardiac output, stroke volume and total peripheral conductance. Endothelin-2 did not have these initial effects in all animals. Subsequently, all peptides increased mean arterial blood pressure and decreased cardiac output and total peripheral conductance. Overall the effects of endothelin-1 and sarafotoxin S6b were very similar, consistent with them acting at the same site. PMID- 2196310 TI - Pulmonary vagal sensory afferents and spontaneous EEG rhythms in the cat sensorimotor cortex. AB - Interactions between vagal afferent fibres and spontaneous electroencephalographic (EEG) activity, recorded on the sensorimotor cortex of the cat, were studied during the mechanical activation of pulmonary afferents. The interactions were compared to the cortical effects of the electrical stimulation of all vagal fibers or to the chemical activation of unmyelinated vagal afferents (C-fibers) by phenyldiguanide. The present study was performed on anesthetized cats, artificially ventilated with open chest. Over 60 locations were explored on the posterior sigmoid gyrus. Repetitive electrical stimulation (30 Hz, 0.8 ms shock duration) of the contralateral cervical vagus nerve or of both nerves induced within less than 5 s changes in the pattern and periodicity of EEG spindles, associated with depressed background rhythms or rhythmic EEG activities. Cortical responses were also observed after i.v. injection of phenyldiguanide. Changes in activity of pulmonary stretch receptors by lung hyperinflation or suppression of phasic lung inflations ('stop pump') had no effect on the EEG rhythms. On the other hand, expiratory threshold loading or passive hyperdeflation of the lungs elicited EEG changes similar to those obtained by electrical stimulation of all vagal fibers. After bilateral vagotomy, all these responses disappeared or were delayed. The present observations strongly suggest that sensory information carried by thin vagal fibers greatly influences cortical rhythms in the cat sensorimotor cortex. PMID- 2196312 TI - [Measurement of estrogen receptor and progesterone receptor in human endometrium and endometrial carcinoma]. AB - The concentration of cytosol estrogen receptors (ER) and progesterone receptors (PR) in the endometrium of the normal menstrual cycle and endometrial carcinoma, were measured by Enzyme Immunoassay (EIA) using monoclonal antibody, and were compared with Dextran Coated Charcoal (DCC) method. In DCC method, maximum binding sites were estimated according to Scatchard plot analysis. Following results were obtained in this study. 1) In the normal endometrium obtained from 20 cases, the correlation coefficients for ER and PR were 0.907 and 0.778, respectively. Regression lines were as follows; ER (EIA) = 1.68 (DCC) + 19.1 fmol/mg protein and PR (EIA) = 0.13 (DCC) + 24.8 fmol/mg protein. A good correlation was found between the two methods in ER assay. 2) In the normal menstrual cycle, DCC values and EIA values of ER were increased in proliferative phase, and were decreased in secretory phase. DCC values of PR were increased in proliferative phase and not decreased in secretory phase, but EIA values of PR were not remarkably changed. 3) In the endometrial carcinoma obtained from 14 cases, there was good correlation between EIA and DCC values in ER assay (r = 0.941), but correlation between the two methods was not found in PR assay. 4) In relation of histology, positive rates were highest in patients with well differentiated types, and in relation of clinical stage, positive rates were higher in the patients with early stages than progressive stages. These results suggest that EIA is as useful as DCC in ER assay in normal endometrium and endometrial carcinoma. PMID- 2196311 TI - [A double blind study of the evaluation of the optimal dose and its frequency in oral administration of OK-432 (Picibanil) by immunological parameters (the 1st report)]. AB - A biological response modifier, OK-432 (Picibanil) administered by injection has been used for cancer immunotherapy. The present study was designed to determine the optimal dose and frequency of oral administration of OK-432. Ninety-one stomach cancer patients were randomly assigned into 7 groups and were administered a placebo or OK-432 at a dose of 5, 20 or 40 KE, once or 3 times a week before their operation (5 KE X 1/W, 20 KE X 1/W, 40 KE X 1/W, or X3/W). ++Missregistration excluded 3 patients and the data of 88 patients were analysed. There was no significant difference in the background status of the patients in each group. The NK activity of PBL was augmented by the administration of 40 KE X 1/W or 20 KE X 3/W and that of RNL was augmented by the administration of 5 KE X 3/W or 40 KE X 1/W, in conjunction with an increase in the number of % positive cells of leu 11a+ or leu 19+ analysed by flow cytometry. The killing activity of PBL, RNL, or MNL against allogeneic lined gastric cancer cells (KATO III) was not augmented by the oral administration of OK-432 for one week. The skin reactivity to Su-PS or PPD, serum levels of tumor markers, or serum levels of immunoglobulins did not help in determining the optimal dose or its frequency. These results suggest that 5 KE X 3/W may be the optimal regimen to augment the antitumor immunity of RNL. PMID- 2196313 TI - [Mechanical studies on casting titanium alloy denture base]. AB - The mechanical properties of the Akers type clasp, bar and frame made by the newly developed Ti-20Cr-0.2Si alloy were studied in order to obtain the indices for designing the cast partial denture base. In the case of the clasp, the bending strength of the Ti-20Cr-0.2Si alloy and pure Ti was lower than that of the Co-Cr alloy. The Ti-20Cr-0.2Si alloy and pure Ti may have the same retentive force as the gold type IV alloy because its bending behavior was similar to that of the gold alloy. In the cyclic bending test, the permanent deflection of the Ti 20Cr-0.2Si alloy was lower than that of the pure Ti and Co-Cr alloy. It had almost the same value as that of the gold alloy. Considering the permanent deflection and fracture, it is preferable that the undercut of the abutment tooth for the Ti-20Cr-0.02Si alloy clasp is 0.50mm or less. The Ti-20Cr-0.2Si alloy bars and frame showed the same bending behavior and strain distribution as the gold alloy. In the case of the Ti-20Cr-0.2Si alloy bar thickened about 30%, the strain was decreased and close to that of the Co-Cr alloy. It was suggested that the Ti-20Cr-0.2Si alloy bar or frame should be designed like the gold alloy. PMID- 2196314 TI - [Familial gingival fibromatosis: report of a case]. AB - One family of familial gingival fibromatosis was presented. Case 1 is an 11 years old girl. Gingival fibromatosis was noted by delayed eruption of permanent teeth. Fibromatosis was seen in whole gingiva and lower 1/2 to 1/3 of the tooth crowns was covered. Gingivectomy was performed. Case 2 was 42 years old man, who was father of case 1. Firstly gingival swelling was noted at the age of 10 years. He had operations of gingivectomy at the age of 28 years. It recurred and fibromatosis was seen in whole gingiva and lower 1/2 to 1/3 of the tooth crowns was covered. Cytogenetically no abnormality was seen in the chromosomes of both cases. Reported cases of familial and non-familial gingival fibromatosis in Japan were reviewed. PMID- 2196315 TI - Tracheostomy--the horizontal tracheal incision. AB - The complication rate after emergency tracheostomy is two to five times greater than after elective procedures. One of the main causes of the high risk of complications in emergency tracheostomy appears to be the amount of time required to open the trachea. Therefore, simple and fast procedures are mandatory. We have developed a new procedure as follows: A horizontal skin incision is performed. Strap muscles are dissected and retracted laterally. A transverse cut between tracheal rings below the thyroid isthmus is performed up to membranous portion of the trachea. The cut ends of the trachea remain open naturally because of the elasticity of the trachea. Skin and tracheal cut-ends are then joined by interrupted sutures. We have used this procedure during the past three years and have not experienced any major complications. This demonstrates the clear advantage and the more physiological nature of the procedure over various other incisions of the tracheal wall. PMID- 2196316 TI - Oncocytoma of the larynx. AB - A case of oncocytoma of the larynx is presented. These lesions are rarely found in the larynx, and have been more commonly described in the salivary and thyroid glands. The histopathological diagnosis is often difficult and the light microscopy can be unreliable for oncocytic lesions. For a more accurate definition of these tumours, the use of histochemical stains together with electron microscopy are advocated. With adequate surgery, the prognosis is excellent, and tumours are unlikely to recur. This paper discusses the management of a patient with a benign oncocytoma of the true vocal cord, and presents a review of the world literature. PMID- 2196318 TI - Kramer v Wilde: an ideological debate. PMID- 2196317 TI - Thorotrast granuloma--a renascence. AB - A case of cervical thorotrast granuloma and its surgical complications is presented. The properties and usage of thorotrast and its later complications are described, and the management of the complications is discussed. It is emphasized that there is usually a long latent period between thorotrast exposure and the advent of complications and perhaps more cases of similar difficulty may be anticipated in the future. PMID- 2196319 TI - Immunolocalization of endosomal cathepsin D in rabbit alveolar macrophages. AB - Intravacuolar proteolysis appears to be an important component of antigen presentation, the activation of peptide hormones, and the conversion of biologically important mediators from inactive precursors. Cathepsin D has been identified in the endosomes of rabbit alveolar macrophages by biochemical analyses [Diment and Stahl, J. Biol. Chem. 260,15311, 1985; Diment et al., J. Biol. Chem. 263,6901, 1988]. Using affinity-purified goat antirabbit cathepsin D IgG, we have localized cathepsin D to the endosomes of rabbit alveolar macrophages. Immunofluorescent staining of frozen sections showed labeling in lysosomes and small vesicles in the periphery of the cell. Label was not seen on the plasma membrane. With immunoperoxidase labeling at the electron microscopic level on cells containing endocytosed mannose-BSA gold, we saw labeling in endosomes and classical lysosomes. When the results were quantitated using immunogold labeling of thin cryosections, we found that the majority of cathepsin D (62.2%) was present in lysosomes, 4.0% in large clear vacuoles, a surprisingly high percentage (29.3%) in small vesicles, 4.9% in endosomes, and none on the plasma membrane. We conclude from this study that, in addition to being present in lysosomes, cathepsin D is present in endosomes and in small peripheral vesicles. PMID- 2196320 TI - Neutrophil accumulation and plasma leakage induced in vivo by neutrophil activating peptide-1. AB - Neutrophil accumulation and plasma leakage induced in rabbit skin by neutrophil activating peptide-1 (NAP-1, a 72 amino acid peptide produced by monocytes and a variety of tissue cells), E. coli endotoxin, and interleukin-1 (IL-1) were compared. Neutrophil accumulation at sites injected with NAP-1 was intense, rapid, and long-lasting; it reached a maximum rate during the first 30 min, continued at constant rate for 4-6 h, and remained detectable up to at least 8 h. In contrast, the neutrophil-attracting effect of endotoxin and IL-1 was slower in onset and more transient; it peaked in the first 2 h and declined to a very low level after 4 h. Plasma leakage induced by NAP-1 had a shorter time course than neutrophil accumulation and ceased after 6 h. Depletion of blood neutrophils by treatment with hydroxyurea prevented the plasma leakage induced by NAP-1 or endotoxin but not by histamine. Desensitization to NAP-1 was studied by restimulation of lesions. Following restimulation with NAP-1 after intervals from 6-10 h, there was diminished infiltration of neutrophils, while nearly normal responses were obtained after an interval of 24 h. Desensitization was dose dependent and affected both plasma leakage and neutrophil accumulation. In lesions initiated with NAP-1 there were normal responses following restimulation with endotoxin but marked desensitization to IL-1, suggesting that NAP-1 may contribute to inflammation induced by IL-1 but not by endotoxin. This study indicates that NAP-1 is a potent mediator of neutrophil accumulation in vivo, with characteristics similar to those reported for C5 fragments, but with a more protracted action. PMID- 2196321 TI - Quantitative comparison of myeloid antigens on five lineages of mature peripheral blood cells. AB - Five-dimensional flow cytometry was used to identify the 5 lineages of peripheral blood leukocytes simultaneously in a single cell preparation. This technique was then used to compare quantitatively the distribution of cell surface antigens on each of these lineages of cells. Neutrophils, eosinophils, basophils, lymphocytes, and monocytes were uniquely identified by correlating their forward and orthogonal light scattering signals with the amount of cell surface-bound IgE. These three cellular characteristics were combined with two additional immunofluorescence labels to create a 5-dimensional space in which each leukocyte population occupied a unique position. The relative quantities of antigens on each cell type were determined for the monoclonal antibodies CD11b, CD13, CD14, CD15, CD16, CD33, CD38, CD45, CD45R, anti-HLA-DR, and anti-Leu-8 labeled with either fluorescein or phycoerythrin. The amount of antigen was described by the mean fluorescence intensity in comparison with the background fluorescence of each cell type. The distribution of the different cell surface antigens on the 5 major leukocyte populations as well as their interdonor variation were then correlated for 10 normal donors. Since none of the antigens studied was lineage specific, it was shown that the different lineages of blood cells could clearly be identified by quantitative comparison of the antigens. This study provides the basis for discrimination between mature cells and immature stages of differentiation of leukocytes and for distinction between normal and leukemic cells. PMID- 2196322 TI - Characteristics of the chemotactic activity of heparin cofactor II proteolysis products. AB - The physiological function of the serpin (serine proteinase inhibitor) heparin cofactor II (HCII) is not well understood. A role for HCII as an inhibitor of thrombin in the presence of dermatan sulfate and heparin has been proposed. Neutrophils (PMN) are the major cellular component of acute inflammation. HCII can be proteolytically inactivated by cathepsin G (CG) and elastase (LE), which are released by stimulated PMN. We have recently shown that reaction products of HCII with CG and LE are potent chemotaxins for PMN. Monocytes (monos) appear later in the course of inflammation than do PMN. They differentiate into macrophages in the tissues and participate in healing of damaged tissue and initiating immune responses. We found that the proteolysis products of HCII were chemotactic for monocytes in a fashion similar to their effects on PMN. At 10(-8) to 10(-9) M, the chemotactic activity of HCII proteolysis products was comparable to that of 10(-8) M N-formyl-Met-Leu-Phe (fMLP). The chemotactic activity of HCII proteinase reaction products is mediated by a different mechanism than that of alpha 1 proteinase inhibitor (alpha 1 PI)-LE complexes or fMLP. Our data suggest that chemotactic activity generated by proteolysis of HCII is not due to the conformational change induced by cleavage of the exposed loop near the reactive site nor by release of the reactive site peptide. We also compared the effects of HCII reaction products and fMLP on expression of Mac-1 and p150,95 adhesive proteins. Mac-1 has been implicated in mono adhesion and chemotaxis and as a potential initiator of coagulation. The surface expression of Mac-1 was not increased above control levels by incubation of leukocytes with HCII digests, even though fMLP did increase surface Mac-1. Proteolysis products of HCII could play a role in the initial influx of PMN into a thrombus, and in the transition from acute to chronic inflammation, or to granulation and healing. PMID- 2196323 TI - Dental education institutionalized: the "what" of the Baltimore College of Dental Surgery. PMID- 2196324 TI - The first dental college: all mortarboard and no bricks. PMID- 2196325 TI - The future of dental education and the Baltimore College of Dental Surgery. PMID- 2196326 TI - The world's first dental college: Why? When? and Where? PMID- 2196327 TI - Concerns about adjuvant chemotherapy for breast cancer. PMID- 2196328 TI - "Avoidable" mortality and health services: a review of aggregate data studies. AB - STUDY OBJECTIVE: The aim of the study was to review published work reporting mortality from conditions amenable to medical intervention and compare the methods used and the results obtained. SOURCE MATERIAL: Two types of analysis were examined: (1) analyses of time trends, relating decline in mortality from amenable conditions to improvements in medical care (3 papers); (2) analyses of geographical variation, either between or within countries, in which mortality was related to the availability of health care resources and to other factors (8 papers). RESULTS: Time-trend studies have in general shown that mortality from amenable causes has declined faster over the past decades than most other causes of death. Studies of geographical variation have shown that mortality from amenable causes is consistently associated with socioeconomic factors, and that the association with the provision of health care resources is rather weak and inconsistent. CONCLUSIONS: (1) The low levels of mortality from amenable causes which presently prevail in industrialised countries are likely to reflect, at least in part, the increased effectiveness of health services; (2) geographical variation in mortality from amenable causes has not yet been shown to reflect differences in effectiveness of health services; and (3) if geographical variation in avoidable mortality does reflect such differences, they must arise from circumstances other than the level of supply, for example from more specific aspects of health care delivery, and are probably closely related to socioeconomic circumstances. In depth studies at the individual level are now more likely to produce information about factors limiting the effectiveness of health services than further studies of aggregate data. PMID- 2196330 TI - What's in the future? PMID- 2196329 TI - Evaluation in health education. A review of progress, possibilities, and problems. PMID- 2196331 TI - HCFA-ball. PMID- 2196332 TI - Coexisting bacterial pyelonephritis and bilateral ureteral fungus balls in a diabetic patient. Case report. AB - Bacterial pyelonephritis is a common precipitating factor in the development of diabetic ketoacidosis. Prompt diagnosis and appropriate antimicrobial therapy usually result in resolution of constitutional symptoms and adequate control of serum glucose. However, occasional cases of presumed bacterial pyelonephritis may not respond to appropriate empiric antibiotic therapy, then causes should be sought such as obstruction or untreated fungal infections of the urinary tract. In this case a diabetic patient with classical pyelonephritis was found to have bilateral ureteral fungus balls as the underlying cause of refractory infection. PMID- 2196333 TI - Trauma systems. Economic and political considerations. AB - Mounting morbidity and mortality from trauma should be viewed as a societal problem. Preventable trauma deaths can be reduced to less than 10% with a regionalized trauma system. Trauma systems, however, incorporating categorization, regionalization, registry data, and prevention efforts, are difficult to design and maintain. As of 1988, only two states had full coverage of all components deemed essential to such a system. Burdens such as uncompensated care, increased malpractice liability, and the need for uniform standards must be overcome to insure survival of trauma systems. PMID- 2196334 TI - Nutritional implications of medication use and misuse in elderly. AB - Factors responsible for an increased risk of drug-nutrient interactions in the elderly are an increased exposure to drug use for chronic health conditions and the greater chance for marginal diets deficient in nutrients. Poor patient compliance and physicians' prescribing patterns further complicate the risk. Several nutrient-drug interactions cause changes in drug efficacy and affect nutritional status. To identify and assess elderly patients at risk, each should be evaluated through socioeconomic, dietary, and clinical parameters. The health care team must be knowledgeable regarding drug interactions to properly intervene using a multidisciplinary approach. An intervention program could prevent a decline in the elderly's health status, reduce healthcare costs and improve the quality of life. PMID- 2196335 TI - Detection of measles virus genomic sequences in SSPE brain tissue by the polymerase chain reaction. AB - The polymerase chain reaction (PCR) was modified to detect RNA genomic sequences by generating cDNA copies of these sequences as a preliminary step. Oligonucleotide primer pairs complementary to sequences in each of the five major structural protein genes of the measles virus (nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, and hemagglutinin protein) were synthesized. PCR products were tentatively identified by visualization of bands of the appropriate size by ethidium bromide staining after gel electrophoresis, and identity was confirmed by subsequent restriction enzyme cleavage of the products at predetermined sites to yield fragments of predicted size. This method successfully amplified 400-500 base regions from each of these five genes in RNA extracts of wild measles virus cultured in Vero cells and in RNA extracted from most of the SSPE brain tissues tested, but not in RNA from any control brain tissues. Measles virus genome was detected in SSPE brain tissues stored frozen for as long as 27 years and formalin-fixed paraffin-embedded subacute sclerosing panencephalitis (SSPE) brain tissues as old as 9 years. This method provides a simple, rapid and highly sensitive means of detecting and identifying sequences of RNA genomes by PCR. The success of this method in detecting measles virus in SSPE brain tissue suggests that PCR is appropriate to investigate the possible presence of RNA viruses in other neurological disorders of unknown etiology. PMID- 2196336 TI - Comparison of enzyme immunoassay with radioimmunoassay for the detection of antibody to hepatitis B core antigen as the only marker of hepatitis B infection in a population with a high prevalence of hepatitis B. AB - Enzyme immunoassay (EIA) and radioimmunoassay (RIA) for the detection of antibody to hepatitis B core antigen (anti-HBc) were compared using serum specimens from Alaska Natives screened during a hepatitis B control program that were initially positive by EIA for only anti-HBc. Of 36 specimens from persons previously HBsAg positive but who were now only anti-HBc positive by EIA, 94.4% were anti-HBc positive by both assays, with anti-HBc levels exceeding 93% inhibition. Low-level antibody to hepatitis B surface antigen (anti-HBs) (less than 10 SRU) and antibody to hepatitis Be (anti-HBe) were also present in 50% and 48% of specimens positive for anti-HBc, respectively. Of 148 specimens from persons initially positive for only anti-HBc by EIA who had no previous documentation of any hepatitis B virus (HBV) infection, 64.5% were positive by repeat testing for anti HBc by both assays, and anti-HBc levels in this sample exceeded 70% in 91.6% and 80.2% of specimens by EIA and RIA, respectively. Low-level anti-HBs and anti-HBe were present in 45.8% and 15.6%, respectively. EIA detection of anti-HBc was found to be less specific than RIA. Of specimens positive for anti-HBc by EIA, 14.8% were negative by RIA. The specificity of the EIA could be improved with respect to RIA by increasing the cut-off from 48% to 68%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196337 TI - Vertical maintenance of dengue-1 virus in sequential generations of Aedes albopictus. AB - Vertical transmission of dengue-1 virus was demonstrated over 3 consecutive generations of Aedes albopictus by tracing descendants of individual, vertically infected females. This study is the first to examine efficiency of vertical transmission of a flavivirus by vertically infected mosquitoes. Vertically infected Ae. albopictus females were more efficient vertical transmitters than females infected by inoculation (i.e., horizontally). Three of 4 vertically infected females examined transmitted virus to their offspring, whereas less than or equal to 0.7% of females infected by inoculation were capable of vertical transmission. PMID- 2196338 TI - Sulfated glucuronyl paragloboside in rat brain microvessels. AB - In patients with neuropathy associated with paraproteinemia, there are monoclonal immunoglobulin M antibodies reacting with myelin-associated glycoprotein and sulfated glucuronyl glycolipids. There are indications that the monoclonal antibodies may be responsible for these neuropathies. However, the mechanism by which the antibodies gain access to the nervous tissue, which is separated by the blood-brain barrier or blood-nerve barrier, is still unknown. In this study, we examined the presence of the sulfated glucuronyl glycolipid antigens on brain endothelial cells. Microvessels were isolated from adult Lewis rat brain cortex. Sulfated glucuronyl paragloboside (SGPG) was detected in the acidic lipid fraction by a TLC immunostaining method. Immunofluorescence studies showed positive staining on the surface of microvessels. In addition, SGPG could be detected in the cultured endothelial cells of human umbilical vein. These findings suggest that the endothelial cells contain antigenic sites for interaction with the autoantibodies. This type of interaction may result in damages to the endothelial cell function and may be responsible for changes in the blood-brain barrier permeability and the ensuing penetration of large molecules, such as immunoglobulins, into the endoneurial space. PMID- 2196339 TI - Role of endogenous taurine on the glutamate analogue-induced neurotoxicity in the rat hippocampus in vivo. AB - The glutamate analogues N-methyl-D-aspartate (NMDA), kainic acid (KA), and quisqualic acid (QA), prepared in different hypertonic media, were perfused in vivo in the hippocampal CA1 field of rats using a microdialysis technique. Extracellular taurine levels, estimated after analysis of the taurine content of dialysates, increased during perfusion of all three agonists but varied according to the osmolarity of the medium. The NMDA-induced increase in extracellular taurine content was only slightly inhibited by perfusion of 150 and 300 mM sucrose. The KA-evoked increase was partially dependent on extracellular osmolarity, because addition of 50 and 150 mM sucrose caused a dose-dependent inhibition that was not augmented using higher sucrose concentrations. QA caused a taurine increase that was totally abolished by addition of 50 mM sucrose. These results indicate that the rise in extracellular taurine level elicited by QA and part of the increase elicited by KA are probably due to a release caused by the cellular swelling that these substances evoke, a finding substantiating the previously proposed osmoregulatory role of taurine. However, almost all the increase in extracellular taurine content caused by NMDA and all the osmotically insensitive part of the KA-evoked rise cannot be explained as release triggered by cell swelling and may reflect a function of taurine other than osmoregulation. PMID- 2196340 TI - Diffuse Lewy body disease in Japan. AB - Thirty-seven Japanese autopsy cases with diffuse Lewy body disease (DLBD) were reviewed from a clinicopathological viewpoint. Based on the neuropathological finding of whether or not many concomitant senile plaques (SPs) and/or neurofibrillary tangles (NFTs) are present. DLBD is divided into two forms: a common form and a pure form. In the common form not only numerous Lewy bodies but also many SPs and/or NFTs are found in the cerebral cortex, whereas in the pure form there are no or few senile changes. Of the 37 cases, 28 cases had the common form, and 9 had the pure form of DLBD. In the common form all cases had shown progressive cortical dementia in the presenile or senile period. About 60% of the cases began with memory disturbance, while 25% showed Parkinson's or Shy-Drager syndrome initially. Parkinson's syndrome, consisting mainly of muscular rigidity and akinesia, was usually marked in the later stage, although there were also 8 cases (28.6%) in which no parkinsonian symptoms were detected even in the terminal stage. On the other hand, almost all cases with the pure form of DLBD showed juvenile Parkinson's syndrome, followed by progressive cortical dementia, although there was one presenile case with mild dementia and Parkinson's syndrome. These Japanese cases are compared with cases reported in Western countries. PMID- 2196341 TI - The hemimedullary syndrome: case report and review of the literature. AB - Hemi-infarction of the medulla causes the clinical constellation of symptoms and signs of both the lateral and medial medullary syndromes and nearly always results from occlusion of an intracranial vertebral artery. In the case reported here, with a clinical diagnosis of hemimedullary syndrome, the expected infarction was imaged by magnetic resonance. A review of the literature confirms that the hemimedullary syndrome, in which both medial and lateral syndromes occur simultaneously, is extremely rare, since it yielded only two previous cases with adequate anatomical confirmation. PMID- 2196342 TI - Cerebrotendinous xanthomatosis: clinical, electrophysiological and nerve biopsy findings, and response to treatment with chenodeoxycholic acid. AB - A 30-year-old patient with cerebrotendinous xanthomatosis was studied over a 6 year period. The clinical manifestations were cataracts, intellectual deterioration, ataxia, palatal and pharyngeal myoclonus, corticospinal tract damage and an electrophysiologically demonstrated sensorimotor peripheral neuropathy. Peripheral motor and sensory nerve conduction velocity was slowed. Sural nerve biopsy revealed reduced densities of both myelinated and unmyelinated axons and teased fibres showed evidence of axonal regeneration and some remyelination. The loss of myelinated nerve fibres particularly affected those of larger diameter, thus contributing to the slowing of nerve conduction. Chenodeoxycholic acid treatment for two separate periods of 10 and 6 months each increased nerve conduction velocity. This electrophysiological improvement was not matched by detectable clinical neurological improvement. PMID- 2196343 TI - Cluster analysis of an insulin-dependent diabetic cohort towards the definition of clinical subtypes. AB - Clinical and biochemical data on 111 consecutive insulin-dependent diabetic children enrolled in a longitudinal prospective study were analyzed to determine if more than one clinical expression of Type I diabetes exists. Use of multivariate statistical methods, including Correspondence Analysis, kappa-means clustering and RECPAM (RECursive Partition and AMalgamation), show that there are two well differentiated clinical expressions of IDDM each characterized by a cluster. One is characterized by later age, less severe onset, longer symptom duration, less beta-cell disappearance after 12 months, more females; the other by earlier age, more sudden and severe onset, DR 3/4, earlier disappearance of beta-cell function and more males. RECPAM analysis provides further insight into the structure of the two clusters. An other RECPAM tree identifies low, medium and high risk groups of disappearance of beta-cell function at 12 months after diagnosis. PMID- 2196344 TI - New bridge for an existing partial denture. PMID- 2196346 TI - New systems for finding information: DENTALPROJ and IO. PMID- 2196345 TI - Spontaneous splenic rupture secondary to angiosarcoma. AB - Angiosarcoma of the spleen is a rare tumor with a very poor prognosis. Review of the world literature reveals only 57 reported cases of this neoplasm. Sixteen of these presented with an acute abdomen secondary to splenic rupture. Patients with this tumor have a mean survival time of 14.4 months after detection, and this decreases to 4.4 months after splenic rupture. The only rational treatment is splenectomy prior to splenic rupture. This paper describes another case presenting as spontaneous splenic rupture. PMID- 2196347 TI - The Li-Fraumeni cancer family syndrome. PMID- 2196349 TI - Carrier detection and prenatal screening of the retinoblastoma gene. PMID- 2196348 TI - Immunohistochemical localization of parathyroid hormone-related protein in parathyroid adenoma and hyperplasia. AB - Parathyroid hormone-related protein (PTHrP) is invoked as the cause of humoral hypercalcaemia of malignancy (HHM); it is contained in the keratinocyte layer of normal skin; and there is evidence that is is produced by fetal parathyroids. Antibodies against synthetic PTHrP peptides have been raised in rabbits and sheep. This immunohistochemical study has found that primary parathyroid adenomata and hyperplastic glands from patients with chronic renal failure stain positively with antisera against PTHrP(1-34) and PTHrP(50-69). Primary hyperplastic glands are negative. No staining with anti-PTHrP(106-141) antiserum could be detected immunohistochemically in any of the parathyroid adenomata or hyperplasia. PMID- 2196350 TI - Natural killer cells in cutaneous malignant melanoma. AB - Using immunocytochemical techniques on fresh surgical samples, a series of 16 cases of cutaneous malignant melanoma (CMM) were examined to characterize further the host inflammatory response. Antibodies to the following cluster of differentiation (CD) antigens were used: CD-3, CD-4, CD-8 (T-cell markers), CD 11b, CD-14 (macrophage marker), CD-16 [an antigen expressed by natural killer (NK) cells and granulocytes], and CD-25. Also examined were a small number of other melanocytic lesions [two cases of lentigo maligna (Hutchinson's melanotic freckle) and five of intradermal naevi]. The results of the study document a population of cells with the morphological and immunophenotypic characteristics of NK cells in association with 10 of the 16 cases of CMM. These cells were consistently absent from the other melanocytic lesions studied. The presence of NK cells in association with some cases of CMM bears no clear relationship to the Breslow thickness, Clark level, tumour ulceration, or the presence of activated T cells as determined by expression of the CD-25 antigen. Whilst an explanation for the significant numbers of NK cells in some CMM lesions in unclear, their presence in intimate association with tumour cells does prompt speculation regarding a possible role in determining the biological behaviour of the tumour. Additionally, the study has confirmed and extended previous findings with respect to the broad characterization of mononuclear cells present in the host infiltrate associated with CMM. PMID- 2196351 TI - Endocrine cells in non-endocrine tumours. PMID- 2196352 TI - Molecular genetics of Duchenne and Becker muscular dystrophy. PMID- 2196353 TI - Double-blind, placebo-controlled trial of alternate-day furosemide therapy in infants with chronic bronchopulmonary dysplasia. AB - To test the hypothesis that alternate-day administration of furosemide will result in a sustained improvement in pulmonary function without causing alterations in electrolyte or mineral homeostasis, we conducted a randomized, double-blind, placebo-controlled study of 11 hospitalized, oxygen-dependent, spontaneously breathing infants with chronic bronchopulmonary dysplasia. Infants were randomly selected to receive either furosemide, 4 mg/kg in two divided doses on alternate days orally, or placebo for 8 days, followed by crossover to the alternate-therapy for an additional 8-day period. The two study periods were separated by a 48-hour washout period. Dynamic compliance, total pulmonary resistance, the concentration of electrolytes in serum, and the concentrations of calcium and creatinine in urine were measured on nontreatment days. Alternate-day furosemide therapy increased dynamic lung compliance by 76 +/- 112% and decreased total pulmonary resistance by 20 +/- 39%, compared with placebo (both variables p = 0.032). Alternate-day furosemide therapy did not result in increased urine output, electrolyte abnormalities, or increased urinary calcium excretion. We conclude that this simplified treatment regimen may be useful in the management of infants with chronic bronchopulmonary dysplasia. The results support our previous speculation that furosemide improves pulmonary function by mechanisms unrelated to its diuretic properties. PMID- 2196354 TI - Frequent handling in the neonatal intensive care unit and intraventricular hemorrhage. AB - The association between periventricular-intraventricular hemorrhage (PV-IVH) and frequent handling resulting from various neonatal intensive care procedures and routine interventions was evaluated in a prospective clinical study. Inborn premature babies with birth weight less than or equal to 1500 gm (n = 156) who did not have PV-IVH or who had grade 1 PV-IVH at less than or equal to 1 hour were randomly assigned to the reduced manipulation protocol (n = 62) or to standard care (n = 94). A bedside microcomputer-based data acquisition system was used to monitor the duration of rest or the number of interventions per day. Infants assigned to receive reduced manipulation spent a significantly higher percentage of time each day at rest than did those who received standard manipulation (p less than 0.006). However, the incidence of grades 2 to 4 PV-IVH did not differ significantly (30% in the study vs 37% in the standard manipulation group). When we analyzed the effect of manipulation in relation to risk of PV-IVH, while taking into account other perinatal variables, standard manipulation was not associated with increased risk of grades 2 to 4 PV-IVH. However, low birth weight, maternal smoking, general anesthesia, early grade 1 PV IVH, low hematocrit, lowest arterial oxygen pressure within the first 6 hours of life, and large base deficit at 6 hours of age all increased the relative risk of grades 2 to 4 PV-IVH. PMID- 2196355 TI - Prenatal and postnatal corticosteroid therapy to prevent neonatal necrotizing enterocolitis: a controlled trial. AB - To determine whether prenatal corticosteroid therapy would reduce the incidence of neonatal necrotizing enterocolitis (NEC), we assigned a total of 466 women admitted in premature labor either to receive placebo (group A, n = 256), if delivery was expected to occur within 24 hours of admission, or to receive betamethasone (group B, n = 210) if delivery was expected to take place more than 24 hours after admission. All women were free of severe medical complications or drug therapy; cases of intrauterine growth retardation or premature rupture of the membranes were excluded. Their newborn infants, excluding malformed, congenitally infected, and growth-retarded infants, were enrolled in the study unless they had died before the age of 10 postnatal days. Babies born to group A mothers (n = 248) were further assigned to a treatment group (group A1, n = 130) receiving dexamethasone, 2 mg/kg/day by intravenous injection during the first 7 days of life, or to a control group (group A2, n = 118) receiving 10% dextrose solution placebo. Group B infants (prenatal betamethasone, n = 205) received neither treatment nor placebo. The incidence of NEC in group A1 was 6.9% (9/130), and in group A2 it was 14.4% (17/118) (p less than 0.05). In group B the incidence was 3.4% (7/205); this was much lower than in group A2 (p less than 0.01) and lower than in group A combined (10.4%) (p less than 0.01). There was no death from NEC and no surgical intervention among group B patients. The mortality rate for group A1 (11%) was lower than for group A2 (56%) (p less than 0.02). There were fewer indications for surgical intervention for NEC in group A1 than in group A2. Histologic studies confirmed bowel ischemia in all specimens analyzed. These data support the hypothesis that the incidence of NEC is significantly reduced after prenatal steroid treatment. Although postnatal therapy with steroids does not decrease the incidence as effectively as prenatal therapy, it improves clinical outcome of NEC. PMID- 2196356 TI - Posttransfusion graft-versus-host disease in infancy. PMID- 2196357 TI - Growth hormone therapy for short stature: panacea or Pandora's box? AB - Increased availability of growth hormone (GH) because of increased production using recombinant DNA technology has led to increased demand. Many children who do not have classic GH deficiency may respond to GH therapy. These observations require rethinking of the medical indications for GH therapy, and raise two central ethical questions: (1) Is it justified to discriminate on the basis of GH deficiency? (2) Whatever the indication for GH treatment, at what height should GH therapy be considered an entitlement? We argue, first, that GH responsiveness, not GH deficiency, should be the criterion for GH treatment, and that prior arguments emphasizing GH deficiency are based on vague or faulty notions of disease, handicap, or potential. Second, we argue that children who are handicapped (arbitrarily defined as including those whose height is below the 1st percentile) and GH responsive are entitled to treatment. Children above that height, whether GH deficient or not, may permissibly be treated, but there is no societal obligation to do so. Such an approach would reduce, though not eliminate, some of the more severe burdens of short stature without aggravating the pernicious effects of "heightism" in American society. PMID- 2196358 TI - Mild hypoglycemia associated with deterioration of mental efficiency in children with insulin-dependent diabetes mellitus. AB - To assess the effects of mild hypoglycemia on cognitive functioning in diabetic children, we used an insulin glucose clamp technique to induce and maintain a hypoglycemic state. Eleven patients, 11 to 18 years of age, completed a series of cognitive tests during a baseline euglycemic state (100 mg/dl (5.5 mmol/L] and repeated those measures at the beginning and end of a hypoglycemic plateau (55 to 65 mg/dl (3.1 to 3.6 mmol/L], and again at restoration of euglycemia. At plasma glucose levels of 60 to 65 mg/dl (3.3 to 3.6 mmol/L), a significant decline in mental efficiency was found. This was most apparent on measures of mental "flexibility" (Trial Making Test) and on measures that required planning and decision making, attention to detail, and rapid responding. Moreover, complete recovery of cognitive function was not contemporaneous with restoration of euglycemia, particularly on those tests requiring rapid responding and decision making (choice reaction time). Not all subjects showed evidence of cognitive impairment during hypoglycemia. The very high degree of intersubject variability suggests that, in addition to plasma glucose values, unknown physiologic variables are responsible for triggering cognitive impairments in school-aged youngsters with diabetes during an episode of mild hypoglycemia. PMID- 2196359 TI - Angiotensin converting enzyme inhibitor therapy to decrease microalbuminuria in normotensive children with insulin-dependent diabetes mellitus. AB - It has been proposed that lowering glomerular pressure in children with insulin dependent diabetes mellitus will reduce microalbuminuria and that this reduction may preserve renal function. We therefore conducted a double-blind, placebo controlled, crossover trial to compare 3 months of treatment with the angiotensin converting enzyme inhibitor captopril (0.9 mg/kg/day), and 3 months of placebo administration to 12 normotensive adolescents with insulin-dependent diabetes mellitus, 11 with microalbuminuria (albumin excretion rate of 15 to 200 micrograms/min) and one with early overt nephropathy. Mean age (+/- SD) was 14.4 +/- 1.7 years, and disease duration was 5.1 +/- 2.5 years. Albumin excretion rate decreased significantly during captopril therapy (baseline 78 +/- 114 micrograms/min; mean of monthly measurements 38 +/- 55 micrograms/min vs placebo 78 +/- 140 micrograms/min; p less than 0.001). During captopril therapy, albumin excretion was reduced by 41 +/- 44% and decreased in 10 of 12 subjects, but was unchanged in two, one with a borderline albumin excretion rate (16.3 micrograms/min) and one with diabetes of short duration (2.9 years). Plasma renin activity rose significantly during captopril therapy, and mean arterial pressure decreased slightly (placebo 81 +/- 7 mm Hg; captopril 76 +/- 5 mm Hg; p = 0.004). After 3 months of captopril treatment, glomerular filtration rate and renal plasma flow did not change significantly. Hemoglobin Alc values remained stable during the study. The only side effect of captopril was diarrhea in one patient. We conclude that, in the short term, captopril is effective in decreasing albumin excretion rate in normotensive children with insulin-dependent diabetes mellitus and microalbuminuria, without significant side effects. Longer trials are indicated in an attempt to delay or prevent overt nephropathy. PMID- 2196360 TI - Comparison of an acellular pertussis-component diphtheria-tetanus-pertussis (DTP) vaccine with a whole-cell pertussis-component DTP vaccine in 17- to 24-month-old children, with measurement of 69-kilodalton outer membrane protein antibody. AB - Healthy 17- to 24-month-old children, previously immunized with three doses of whole-cell diphtheria-tetanus-pertussis (DTP) vaccine, were enrolled in a multi center double-blind, randomized study comparing a DTP vaccine with an acellular pertussis-component (APDT) and a conventional whole-cell pertussis-component DTP vaccine. Thirty-eight children received APDT vaccine, and 37 children received DTP vaccine. APDT vaccine recipients had significantly less local pain and warmth than DTP vaccine recipients. Antibody responses to lymphocytosis-promoting factor were similar in the two groups. The APDT vaccine recipients had a higher IgG antibody response to filamentous hemagglutinin than the DTP vaccinees had. Equivalent agglutinin responses were seen in the two groups. The APDT vaccine recipients had a significantly better antibody re-enzyme-linked immunosorbent assay, than DTP vaccinees had 1 month and 1 year after immunization. This APDT vaccine was immunogenic and caused fewer local reactions than conventional DTP vaccine when administered as a fourth dose to 17- to 24-month-old children. PMID- 2196362 TI - Operational aspects of bioreactor contamination control. AB - The contamination-free operation of a bioreactor demands constant attention to details. Assuming a well-designed and validated system exists, contamination control requires a skilled operating staff, clear and concise standard operating procedures, ongoing operations review and training, thorough cleaning of equipment, and an effective preventative maintenance program. This paper highlights basic operational aspects of contaminant-free bioreactor operation from inoculum development to bioreactor harvesting. PMID- 2196361 TI - Stress hyperglycemia in childhood: a very high risk group for the development of type I diabetes. PMID- 2196364 TI - A participatory planning process for wheelchair selection. PMID- 2196363 TI - The use of oil-in-water emulsions as a vehicle for parenteral drug administration. AB - Oil-in-water emulsion formulations are useful for the parenteral administration of drugs which have significant delivery problems. Drugs may be incorporated into emulsion formulations either by emulsification of the drug dissolved in the oil phase, or by extemporaneous addition of a concentrated solution in a cosolvent to a commercial i.v. emulsion. Examples are given of the use of parental emulsion dosage forms for the delivery of drugs which have low water solubility, lack stability to hydrolysis, are irritant or have substantial affinity for plastic infusion sets. These examples are largely drawn from studies of novel cytotoxic agents. Emulsion dosage forms may also have some potential for site-directed drug delivery or for sustained release applications. The potential hazards of parenteral emulsions and some of the means of size determination of the dispersed oil droplets are also examined. PMID- 2196365 TI - Some physiological studies on fungi isolated from poultry feedstuffs. AB - A total of 506 isolates of mesophilic, thermophilic and thermotolerant fungi isolated from the poultry feed ingredients included soybean meals, ground maize, cottonseed cake, wheat bran and fish meal, on glucose-Czapek's agar, Littman oxgall agar at 28 degrees C and yeast starch agar (YPSs) at 45 degrees C, were screened for their ability to produce hydrolytic protease enzyme on solid media. Most of the fungal isolates were able to produce such enzymes but with variable capabilities. The highest proteolytic activity was exhibited by some isolates of Penicillium chrysogenum, Aspergillus flavus, Thermoascus thermophilus and Rhizopus chizopodifarmis. Of all fungal isolates screened for proteolytic activity, Penicillium chrysogenum and Thermoascus thermophilus produced the highest amounts of proteases. These two isolates were used to study the effect of some environmental and nutritional factors on their proteolytic activity. It was found that the highest yield of protease by P. chrysogenum (12.5 units) was achieved 3 days after incubation at 30 degrees C. Marked reduction in protease activity was observed at 37 degrees C. The thermophilic fungus T. thermophillus exhibited maximum (18 units) proteolytic activity 6 days after incubation at 45 degrees C. The enzyme yield was reduced to 13 units at 50 degrees C. Among the seven carbon sources tested, sucrose was the most appropriate for maximum protease production by both P. chrysogenum and T. thermophilus (13.2 and 12.8 units, respectively). Of the sixteen nitrogen sources investigated, NaNO3 was the best inorganic additive nitrogenous salt which induced the highest proteolytic activity by P. chrysogenum and T. thermophilus, whereas DL-tryptophan was the most preferable organic nitrogen compound for maximum protease production by the two fungi tested. PMID- 2196366 TI - [Detection mechanism of verbal and environmental sounds]. PMID- 2196367 TI - Silent myocardial ischaemia: prevalence, pathophysiology and significance. AB - It is now generally accepted that in many individuals with ischaemic heart disease the bulk of transient 'ischaemic activity' is asymptomatic or silent. Moreover, a substantial proportion of acute myocardial infarctions occur without symptoms. Transient episodes of silent ischaemia (SI) may often occur in the absence of any evidence of an increase in myocardial demand. In line with this is the fact that they are usually associated with periods of normal, low levels of, physical activity and may occur at rest and during sleep. These findings imply that myocardial oxygen supply, mediated largely by coronary vasomotion, may be an important factor in the aetiology of SI: although in many instances myocardial demand is also important. Ischaemic activity in patients with coronary heart disease exhibits a circadian variation, with a peak in the morning and a smaller secondary peak in the early evening. This rhythm may also reflect, in part, an underlying variation in coronary artery tone. The prognostic significance of SI has still to be fully determined. Its frequency in daily life in individuals with proven coronary heart disease is related to recognised prognostic indicators on standard exercise testing, indicating potential prognostic importance. There is reasonably substantial evidence that the frequency and duration of SI in some patients with unstable angina, despite full medical treatment, is an important determinant of short- and long-term outcome. Limited data indicate that the frequency of SI during ambulant activity may also be of prognostic importance in some survivors of myocardial infarction. In patients with stable coronary heart disease, SI during exercise testing carries the same adverse prognosis as symptomatic ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196368 TI - J-shaped curves. AB - Antihypertensive treatment trials with more than 14,000 treated patients have indicated a J- or U-shaped relationship between achieved blood pressure (BP) and coronary heart disease (CHD) risk. However, similar studies involving more than 16,000 treated patients have not found such a relationship, only a rather flat response. Analysis bias may partly be responsible for the different results, but the findings of a non-linear relationship do appear to be significant in several of the studies. Pre-existing myocardial ischaemia (with or without symptoms) may explain some of the cases with increased CHD risk at low BP levels, but not others, However, myocardial ischaemia may still be a cause of the increased risk when BP is excessively lowered due to reduced myocardial autoregulatory reserve. In the long term it would appear reasonable to 'normalise' the BP as much as is possible. However, the question is whether a more gradual reduction would be advisable in some cases. As yet we do not know in which patients this would be so, hence at present no change of treatment practices are recommended. PMID- 2196369 TI - Problems in the measurement of blood pressure. AB - Several placebo-controlled trials have established the value of drug treatment in even mild hypertension. It is axiomatic, however, that prior to treatment of an individual patient it be known that blood pressure is consistently elevated. In addition, assessment of the value of any particular form of therapy depends upon the accurate measurement of blood pressure. Unfortunately current evidence would suggest that neither of these prerequisites pertain. This paper reviews the evidence for this and discusses ways of improving clinical practice. PMID- 2196370 TI - Effects of dilevalol, propranolol and placebo on retinal blood flow, blood pressure and heart rate: a double-blind study. PMID- 2196371 TI - Dilevalol: a dose-response study in normal volunteers. AB - Dilevalol, 100 mg, 200 mg and 400 mg, and placebo were given to eight normal volunteers and the effect on blood pressure and heart rate studied at rest and on exercise. There was a dose-dependent fall in exercising heart rate and in the increased heart rate on exercise with dilevalol, while exercising systolic blood pressure and the rise in systolic blood pressure on exercise fell dose dependently up to 200 mg, but the effect of 400 mg was similar. Diastolic blood pressure was not affected. Supine heart rate and blood pressure changes were not different from placebo. Tilt heart rate fell most constantly from 200 mg. Some fall in tilt systolic blood pressure was seen but this was not dose-dependent, diastolic blood pressure was not affected. There was wide variation in plasma concentration of dilevalol, as might be expected from a liver metabolised drug, with a relatively larger amount absorbed of the 400 mg dose compared to the 100 or 200 mg doses. PMID- 2196372 TI - Randomised, double-blind, three-way cross-over study of dilevalol 200 and 400 mg and atenolol 100 mg once-daily in patients with chronic stable angina pectoris. AB - Eighteen male patients (aged 40-66 years) with confirmed ischaemic heart disease and a minimum of four angina attacks per week were included in a double-blind comparison of dilevalol 200 mg, dilevalol 400 mg and atenolol 100 mg. Following a one-week placebo run-in period patients were randomly allocated to one of the three treatments, after which they crossed to the remaining two treatments according to a balanced Latin square design. Each treatment was given once-daily over four weeks. Symptom-limited treadmill exercise testing using a modified Bruce protocol was performed at the end of placebo, and after each treatment around 24 hours post-dosing. The mean exercise time on placebo was 7.0 (+/- 0.91) minutes which changed to 7.8 (+/- 0.93) minutes on dilevalol 200 mg, 7.3 (+/- 0.88) minutes on dilevalol 400 mg and 8.2 minutes (+/- 1.06) on atenolol 100 mg. Nine patients had a greater exercise tolerance on dilevalol (200 or 400 mg), and nine a greater exercise tolerance on atenolol. Maximum exercise heart rate on placebo was 113 (+/- 5.0) beats per minute (bpm) which was reduced to 101 (+/- 3.6), 96 (+/- 2.7) and 98 (+/- 4.9) bpm. on dilevalol 200 mg, dilevalol 400 mg and atenolol 100 mg, respectively. Correspondingly, the rate-pressure product was reduced from 18.1 (x 10(3)) units on placebo to 14.8, 13.4 and 14.4 (x 10(3)) units on each treatment. Pairwise comparisons by the least square mean procedure showed no significant differences between treatments for any of the measured parameters. All treatments caused a reduction in both angina attack rates and trinitrate consumption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196373 TI - Knowledge and competency in medicine. PMID- 2196374 TI - Direct protein sequencing of wheat mitochondrial ATP synthase subunit 9 confirms RNA editing in plants. AB - RNA editing, a process that results in the production of RNA molecules having a nucleotide sequence different from that of the initial DNA template, has been demonstrated in several organisms using different biochemical pathways. Very recently RNA editing was described in plant mitochondria following the discovery that the sequence of certain wheat and Oenothera cDNAs is different from the nucleotide sequence of the corresponding genes. The main conversion observed was C to U, leading to amino acid changes in the deduced protein sequence when these modifications occurred in an open reading frame. In this communication we show the first attempt to isolate and sequence a protein encoded by a plant mitochondrial gene. Subunit 9 of the wheat mitochondrial ATP synthase complex was purified to apparent homogeneity and the sequence of the first 32 amino acid residues was determined. We have observed that at position 7 leucine was obtained by protein sequencing, instead of the serine predicted from the previously determined genomic sequence. Also we found phenylalanine at position 28 instead of a leucine residue. Both amino acid conversions, UCA (serine) to UUA (leucine) and CUC (leucine) to UUC (phenylalanine), imply a C to U change. Thus our results seem to confirm, at the protein level, the RNA editing process in plant mitochondria. PMID- 2196375 TI - Crystal structure of thermitase at 1.4 A resolution. AB - The crystal structure of thermitase, a subtilisin-type serine proteinase from Thermoactinomyces vulgaris, was determined by X-ray diffraction at 1.4 A resolution. The structure was solved by a combination of molecular and isomorphous replacement. The starting model was that of subtilisin BPN' from the Protein Data Bank, determined at 2.5 A resolution. The high-resolution refinement was based on data collected using synchrotron radiation with a Fuji image plate as detector. The model of thermitase refined to a conventional R factor of 14.9% and contains 1997 protein atoms, 182 water molecules and two Ca ions. The tertiary structure of thermitase is similar to that of the other subtilisins although there are some significant differences in detail. Comparison with subtilisin BPN' revealed two major structural differences. The N-terminal region in thermitase, which is absent in subtilisin BPN', forms a number of contacts with the tight Ca2+ binding site and indeed provides the very tight binding of the Ca ion. In thermitase the loop of residues 60 to 65 forms an additional (10) beta-strand of the central beta-sheet and the second Ca2+ binding site that has no equivalent in the subtilisin BPN' structure. The observed differences in the Ca2+ binding and the increased number of ionic and aromatic interactions in thermitase are likely sources of the enhanced stability of thermitase. PMID- 2196376 TI - Genetic approach to the role of tryptophan residues in the activities and fluorescence of a bacterial periplasmic maltose-binding protein. AB - The periplasmic maltose-binding protein (MBP or MalE protein) of Escherichia coli is an essential element in the transport of maltose and maltodextrins and in the chemotaxis towards these sugars. On the basis of previous results suggesting their possible role in the activity and fluorescence of MBP, we have changed independently to alanine each of the eight tryptophan residues as well as asparagine 294, which is conserved among four periplasmic sugar-binding proteins. Five of the tryptophan mutations affected activity. In four cases (substitution of Trp62, Trp230, Trp232 and Trp340), there was a decrease in MBP affinity towards maltose correlated with modifications in transport and chemotaxis. According to the present state of the 2.3 A three-dimensional structure of MBP, all four residues are in the binding site. Residues Trp62 and Trp340 are in the immediate vicinity of the bound substrate and appear to have direct contacts with maltose; this is in agreement with the drastic increases in Kd values (respectively 67 and 300-fold) upon their substitution by alanine residues. The modest increase in Kd (12-fold) observed upon mutation of Trp230 would be compatible with the lesser degree of interaction this residue has with the bound substrate and the idea that it plays an indirect role, presumably by keeping other residues involved directly in binding in their proper orientation. Substitution of Trp232 resulted in a small increase in Kd value (2-fold) in spite of the fact that this residue is the closest to the ligand of the tryptophan residues according to the three-dimensional model. In the fifth case, replacement of Trp158, which is distant from the binding site, strongly reduced the chemotactic response towards maltose without affecting the transport parameters or the sugar-binding activities of the mutant protein. Trp158 may therefore be specifically implicated in the interaction of MBP with the chemotransducer Tar, but this effect is likely to be indirect, since Trp158 is buried in the structure of MBP. Of course, some structural rearrangements could be responsible in part for the effects of these mutations. The remaining four mutations were silent. The corresponding residues (Trp10, Trp94, Trp129 and Asn294) are all distant from the sugar-binding site on the crystallographic model of MBP, which is in agreement with their lack of effect on binding. In addition, our results show that they play no role in the interactions with the other proteins of the maltose transport (MalF, MalG or MalK) or chemotaxis (Tar) systems.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2196377 TI - Synaptic intermediates promoted by the FLP recombinase. AB - We have devised a novel assay to trap nucleoprotein synaptic intermediates of the FLP recombination reaction. DNase I footprinting analysis of these intermediates indicates that synapsis is mediated by protein-protein interactions between FLP molecules bound to each FLP recombination target (FRT) site. Under certain conditions we have observed a synaptic structure in which the FRT sites have come together in an aberrant arrangement. Although our analysis shows that homology between the core sequences of the sites is not a prerequisite for synapsis, the data suggest that homology between cores dictates the directionality of the reaction. Many of the intermediates contain a Holliday junction indicating that the FLP protein has catalysed strand exchanges between the FRT sites. The general scheme of the assay should prove useful to analyse nucleoprotein intermediates in other site-specific recombination systems, and to investigate protein-protein and protein-DNA interactions in intermediates important for DNA replication and transcription. PMID- 2196378 TI - Structural organization of flagellin. AB - The terminal regions of flagellin from Salmonella typhimurium have been reported to be disordered in solution, whereas the central part of the molecule contains protease-resistant, compact structural units. Here, conformational properties of flagellin and its proteolytic fragments were investigated and compared to characterize the domain organization and secondary structure of flagellin. Deconvolution analysis of the calorimetric melting profiles of flagellin and its fragments suggests that flagellin is composed of three co-operative units or domains. The central part of the molecule, residues 179 to 418, consists of two domains (G1 and G2), whereas the third domain (G3) is discontinuous, constructed from segments 67 to 178 and 419 to 448. Secondary structure prediction and analysis of far-ultraviolet circular dichroic spectra have revealed that G1 and G2 consist predominantly of beta-structure with a little alpha-helical content. G3 contains almost equal amounts of alpha and beta-structure, while in the terminal parts of flagellin the ordered secondary structure seems to be entirely alpha-helical. PMID- 2196379 TI - Chronic alcoholism and male sexual dysfunction. AB - Chronic alcoholism can profoundly influence marital relationships, but the nature of the effect of alcohol abuse on sexual interactions is not clear. This article critically reviews information on the prevalence of sexual disorders and possible endocrine, neurologic, and psychologic processes that may mediate the effects of chronic alcoholism on male sexual functioning. Emphasis is placed on a conceptual model that integrates biologic and psychologic perspectives, moving away from simplistic unidimensional approaches to the study of the behavioral effects of this serious medical and social problem. PMID- 2196380 TI - Human adenovirus-host cell interactions: comparative study with members of subgroups B and C. AB - Host cell interactions of human adenovirus serotypes belonging to subgroups B (adenovirus type 3 [Ad3] and Ad7) and C (Ad2 and Ad5) were comparatively analyzed at three levels: (i) binding of virus particles with host cell receptors; (ii) cointernalization of macromolecules with adenovirions; and (iii) adenovirus induced cytoskeletal alterations. The association constants with human cell receptors were found to be similar for Ad2 and Ad3 (8 x 10(9) to 9 x 10(9) M-1), and the number of receptor sites per cell ranged from 5,000 (Ad2) to 7,000 (Ad3). Affinity blottings, competition experiments, and immunofluorescence stainings suggested that the receptor sites for adenovirus were distinct for members of subgroups B and C. Adenovirions increased the permeability of cells to macromolecules. We showed that this global effect could be divided into two distinct events: (i) cointernalization of macromolecules and virions into endocytotic vesicles, a phenomenon that occurred in a serotype-independent way, and (ii) release of macromolecules into the cytoplasm upon adenovirus-induced lysis of endosomal membranes. The latter process was found to be type specific and to require unaltered and infectious virus particles of serotype 2 or 5. Perinuclear condensation of the vimentin filament network was observed at early stages of infection with Ad2 or Ad5 but not with Ad3, Ad7, and noninfectious particles of Ad2 or Ad5, obtained by heat inactivation of wild-type virions or with the H2 ts1 mutant. This phenomenon appeared to be a cytological marker for cytoplasmic transit of infectious virions within adenovirus-infected cells. It could be experimentally dissociated from vimentin proteolysis, which was found to be serotype dependent, occurring only with members of subgroup C, regardless of the infectivity of the input virus. PMID- 2196381 TI - Feedback regulation of human immunodeficiency virus type 1 expression by the Rev protein. AB - Rev is an essential regulatory protein of the human immunodeficiency virus type 1 (HIV-1) that affects the transport and half-life of certain viral mRNAs. Rev exerts its function via a unique element, the Rev-responsive element (RRE), located within the env region of HIV-1. It has been previously demonstrated that Rev affects the relative levels of RRE-containing and RRE-lacking mRNAs. We have studied the effects of Rev on the expression of the three different groups of small, multiply spliced mRNAs that lack the RRE sequence and encode the regulatory proteins Tat, Rev, and Nef. To monitor the tat, rev, and nef mRNAs we generated specific S1 nuclease mapping probes that distinguish among them. Analysis of all the mRNA species producing Tat, Rev, and Nef revealed that their levels are coordinately regulated by Rev. They are increased in the absence of Rev protein and are down regulated in the presence of Rev. The corresponding proteins were measured by immunoprecipitations, and their levels are in agreement with the RNA levels. These results verify the model proposing that Rev is a general regulator indirectly affecting all the multiply spliced mRNAs to a similar extent. Therefore, Rev down regulates its own expression and the expression of Tat and Nef. PMID- 2196382 TI - Conformational changes and fusion activity of influenza virus hemagglutinin of the H2 and H3 subtypes: effects of acid pretreatment. AB - Marked differences were observed between the H2 and H3 strains of influenza virus in their sensitivity to pretreatment at low pH. Whereas viral fusion and hemolysis mediated by influenza virus X:31 (H3 subtype) were inactivated by pretreatment of the virus at low pH, influenza virus A/Japan/305/57 (H2 subtype) retained those activities even after a 15-min incubation at pH 5.0 and 37 degrees C. Fusion with erythrocytes was measured by using the octadecylrhodamine dequenching assay with both intact virions and CV-1 monkey kidney cells expressing hemagglutinin (HA) on the plasma membrane. To study the nature of the differences between the two strains, we examined the effects of low-pH treatment on the conformational change of HA by its susceptibility to protease digestion, exposure of the fusion peptide, and electron microscopy of unstained, frozen, hydrated virus. We found that the respective HA molecules from the two strains assumed different conformational states after exposure to low pH. The relationship between the conformation of HA and its fusogenic activity is discussed in the context of these experiments. PMID- 2196383 TI - Q beta RNA bacteriophage: mapping cis-acting elements within an RNA genome. AB - We have identified, for the first time, regions of cis-acting RNA elements within the bacteriophage Q beta replicase cistron by analyzing the infectivities of 76 replicase gene mutant phages in the presence of a helper replicase. Two separate classes of mutant Q beta phage genomes (35 different insertion mutants, each containing an insertion of 3 to 15 nucleotides within the replicase gene, and 41 deletion genomes, each having from 15 to 935 nucleotides deleted from different regions of the gene) were constructed, and their corresponding RNAs were tested for the ability to direct the formation of progeny virus particles. Each mutant phage was tested for plaque formation in an Escherichia coli (F+) host strain that supplied helper Q beta replicase in trans from a plasmid DNA. Of the 76 mutant genomes, 34% were able to direct virus production at or close to wild-type levels (with plaque yield ratios of greater than 0.5), another 36% also produced virus particles, but at much lower levels than those of wild-type virus (with plaque yield ratios of less than 0.05), and the remaining 30% produced no virus at all. From these data, we have been able to define regions within the Q beta replicase gene that contain functional cis-acting RNA elements and further correlate them with regions of RNA that are solely required to code for functional RNA polymerase. PMID- 2196384 TI - Mutational analysis of a native substrate of the human immunodeficiency virus type 1 proteinase. AB - Proteolytic processing of the gag/pol precursor by the human immunodeficiency virus type 1 proteinase is essential for the production of infectious viral particles. Although the sites of virus-specific cleavages have been determined, the primary amino acid sequences surrounding these sites are heterogeneous and the determinants that direct the cleavage specificity exhibited by human immunodeficiency virus type 1 proteinase remain largely undefined. We performed mutational analysis of the Tyr/Pro site, which produces the amino terminus of the viral capsid protein, and the Phe/Pro site, which produces the amino terminus of the proteinase. Mutations were made in a clone encoding a frameshift mutation that results in the expression of equimolar amounts of the substrate and proteinase in the form of a truncated gag/pol precursor. After single-amino-acid substitutions were made, their effects on proteolytic processing were examined by in vitro transcription and in vitro translation of the synthetic mRNA; translation products were then processed by exogenously added purified proteinase. Single-amino-acid substitutions yielded both substrates which were processed with wild-type efficiency and substrates on which processing was impaired. At the Tyr/Pro site in gag, processing was severely inhibited by substitutions within the P4, P2, P1, and P2' positions. The Phe/Pro site in pol, however, demonstrated far greater tolerance to amino acid substitution. These data suggest that the primary amino acid sequence around a scissile bond is more critical for cleavage of the Tyr/Pro site than the Phe/Pro site. PMID- 2196386 TI - Hepatitis B virus X protein produced in Escherichia coli is biologically functional. AB - The hepatitis B virus X gene product trans activates transcription from a variety of viral and cellular regulatory elements. We expressed the complete, nonfused X protein in Escherichia coli and showed it to be active in trans activating a human immunodeficiency virus long terminal repeat-linked chloramphenicol acetyltransferase reporter gene. PMID- 2196385 TI - T-cell lymphoma lines derived from rat thymomas induced by Moloney murine leukemia virus: phenotypic diversity and its implications. AB - The phenotype of 27 Moloney murine leukemia virus-induced rat thymic lymphomas and 36 cell lines derived from these tumors was determined by using 18 monoclonal antibodies directed against hematopoietic cell surface determinants. The cell lines and the primary tumors from which they were derived were clonally related as determined by the pattern of provirus integration and the pattern of rearrangement of the T-cell receptor beta and delta and Igh loci. The differentiation phenotype of the primary tumors and the cell lines derived from them were related. The differences observed between the primary tumors and the cell lines could be explained either by the selection of subpopulations of tumor cells during establishment in culture or by the phenotypic instability of the tumor cells. One cell line (LE3Sp) underwent the transition from a CD4+ CD8+ to a CD4+ CD8- phenotype following exposure to interleukin-2 in culture. Both the primary tumors and the cell lines derived from them express a wide range of phenotypes which correspond to multiple stages in T-cell development. This observation suggests that the pleiomorphism of retrovirus-induced lymphomas, which had been suggested previously from the analysis of mouse tumors, is an intrinsic property of the process of oncogenesis and is not due to the transformation of different types of cells by spontaneously arising leukemogenic variants of the inoculated virus. The wide spectrum of phenotypes expressed by these tumors suggests that Moloney murine leukemia virus may infect and transform T cells at various stages of development. Alternatively, the target cells may be immature T-cell precursors which, following transformation, continue to differentiate. A host of early findings, suggesting that the repertoire of target cells is restricted to poorly differentiated hematopoietic progenitors, and the ability of the LE3Sp cell line to differentiate in culture indicate that the latter possibility may be more likely. The data in this report address the extent and mechanism of the phenotypic variability of retrovirus-induced rodent T-cell lymphomas. In addition, they demonstrate the potential usefulness of the T-cell lymphoma lines we have established in studies of oncogenesis and T-cell differentiation. PMID- 2196389 TI - Sonographic diagnosis of venocclusive disease of the liver and danazol therapy for autoimmune thrombocytopenia in an autologous marrow transplant patient. AB - A 16-Year-old boy with lymphoblastic lymphoma underwent an autologous bone marrow transplantation (ABMT) after conditioning with high-dose busulfan and cyclophosphamide. On day 39 post-transplant, right upper quadrant pain occurred with an increase in the size of the liver. Liver function tests showed a subsequent deterioration. Ultrasonographic studies of the abdomen disclosed hepatosplenomegaly, ascites, thickening of the gall bladder wall and a failure to visualize the major hepatic veins. The venocclusive disease of the liver (VOD) diagnosis was confirmed from these findings. Ultrasonographic monitoring reflected the disease status well and demonstrated a complete recovery from the VOD. We emphasize, thus, that abdominal ultrasonography can be applied easily, being a non-invasive procedure, and is useful in diagnosing VOD. Furthermore, the procedure can be repeated serially for evaluating the severity of VOD. Although engraftment was confirmed with granulocytes exceeding 500/microliters, platelet recovery was delayed; the megakaryocytes had not decreased in bone marrow aspirates and platelet-associated IgG was significantly elevated. Since autoimmune thrombocytopenia was highly suspected, to prevent immunosuppression danazol was given as an immune modulator instead of prednisolone, and a complete recovery was obtained. Accordingly, danazol can be used as an alternative to prednisolone for the treatment of autoimmune thrombocytopenia after bone marrow transplantation. PMID- 2196388 TI - Primary lung cancer in an 18-year-old boy: case report. AB - An autopsy case of an 18-year-old boy with adenocarcinoma of the lung is reported. He experienced dyspnea and hemosputum in July 1988. Chest radiographs showed a diffuse bilateral streaky shadow, bilateral pleural effusion and cardiac enlargement. The diagnosis of adenocarcinoma was made by transbronchial biopsy at another hospital. He visited the National Cancer Center Hospital on October 7, 1988. The diagnosis of lung cancer was strongly suggested by positive immunohistochemical staining for pulmonary surfactant apoprotein in biopsy specimens from supraclavicular lymph nodes. Intensive systemic survey demonstrated no other primary site than the lung. The patient was treated with cisplatin, adriamycin and etoposide and his subjective symptoms such as cough and dyspnea significantly improved over the next three months. Tumor shadows in the lung increased steadily, however after February, 1989. A significant lymphangitic spread of the carcinoma and marked obsteoblastic bone metastases were revealed at autopsy. PMID- 2196387 TI - Inducible nuclear factor binding to the kappa B elements of the human immunodeficiency virus enhancer in T cells can be blocked by cyclosporin A in a signal-dependent manner. AB - Cyclosporin A (CsA) is thought to exert its immunosuppressive effects by inhibiting the expression of a distinct set of lymphokine genes which are induced upon T-cell activation, among them the gene coding for interleukin-2. In addition, the activation of the human immunodeficiency virus (HIV) is partially suppressed. To better understand the molecular mechanisms underlying suppression by CsA, we have investigated the effects of this drug on transcription factors in T cells. Here we report that the formation of two distinct mitogen-inducible DNA binding complexes, the kappa B complex within the HIV enhancer and the NFAT-1 complex within the interleukin-2 enhancer, is inhibited in the presence of CsA. The kappa B-binding activity with the HIV enhancer is inhibited only if it is activated via the mitogen phytohemagglutinin whereas phorbol myristate acetate mediated activation is completely insensitive to the drug. This suggests a model in which functionally indistinguishable kappa B complexes can be activated via two separate pathways of signal transduction distinguishable by CsA. PMID- 2196390 TI - A case of ovarian cystadenocarcinoma associated with pregnancy. AB - A case of ovarian cystadenocarcinoma associated with pregnancy is reported. The semicystic left ovarian tumor was found in a 28-year-old woman, gravida 2, para 1 at 33 weeks' gestation. A primary Cesarean section, total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by chemotherapy were performed. The histological examination revealed the tumor to be a serous cystadenocarcinoma. The patient and infant have both remained well and free of disease for the eight years which have elapsed since the therapy started. PMID- 2196391 TI - [Pilomatrix carcinoma--report of the second case in Japan and a review of the literature]. AB - A 53-year-old man had a rapidly growing tumor, measured 3 cm in diameter, on his left temporal region of 2 months' duration. The lesion showed histological resemblance to pilomatricoma but differed by the presence of irregular nests of atypical basophilic cells (basaloid cells) with focal squamoid differentiation and a large number of atypical mitoses. A review of 16 cases of pilomatrix carcinoma documented since the year of 1980 indicated that this tumor occurs in males three times more frequently than in females. 75% of all patients were over forty years old. Recurrences were seen in 6 of the 10 patients whose tumor had been resected simply, but there was no evidence of recurrence in the 4 patients with a wide resection of tumor. PMID- 2196392 TI - [Diagnosis of intra-abdominal complications in the early postoperative period]. PMID- 2196393 TI - [Invasive interventions under the control of ultrasonic scanning in diseases of the abdominal organs]. PMID- 2196394 TI - [Cholelithiasis (mechanisms of lithogenesis and current aspects of treatment)]. PMID- 2196395 TI - [Antiviral therapy of generalized herpes infection]. PMID- 2196396 TI - [Pressor-depressor factors in renal vein blood in patients with renovascular hypertension]. AB - Development of renovascular hypertension was investigated in 68 patients. Interrelated defects found in components of renal pressor-depressor system may be a contributing factor in the disease onset. Contralateral pressor-depressor system is the first to start regulating deranged regional and general hemodynamics in functional failure of the kidneys. In organic lesion occurring in the affected kidney later than in the contralateral one, there is compensatory depressor activation upon the distress of the pressor function. This may be aimed at maintenance of adequate microcirculatory blood flow and metabolism. PMID- 2196397 TI - [Prognosis of clinical course in stomach ulcer]. AB - Basing on a complex of significant clinical signs of the disease and mathematical methods, algorithms and methodology of prognosticating a course, outcome and complications of gastric ulcer have been developed. The system may be used in variants of automatic and table processing of clinical data. PMID- 2196398 TI - [Combined diagnosis of focal hepatic lesions in repeated surgery of the liver]. PMID- 2196399 TI - Expression of ras oncogene p21 protein in esophageal squamous cell carcinoma. AB - In order to investigate the value of ras oncogene expression as a prognostic indicator in esophageal squamous cell carcinoma, we evaluated the level of ras oncogene protein product (p21) in 52 specimens resected between 1977 and 1986. All patients were followed until death or for at least 2 years. Pathology slides and archival paraffin blocks were retrieved for confirmation of the original diagnosis, study of histopathologic features, and measurement of p21 content. P21 titers were obtained using the RAP-5 monoclonal antibody in a semiquantitative immunohistochemical assay. Titer was expressed as the highest dilution of antibody giving definitive staining using the avidin-biotin peroxidase method. Ras oncogene was expressed in 88.5% of the specimens. We did not find a significant correlation between ras expression and any of a variety of clinical and histopathologic prognostic parameters. Although patients' median survival after resection of specimens with ras oncogene expression was less than half the median survival after removal of tumors without such expression, this difference was not statistically significant. Further prospective investigations are needed to assess the role of ras oncogene evaluation in clinical practice. PMID- 2196400 TI - Surgical treatment of the cancer patient: preoperative assessment and perioperative medical management. AB - Cancer patients undergoing surgery often present with unusual and challenging problems. Their age and the fact that they are often chronically ill place them at increased surgical risk. In many instances the need for surgical intervention is crucial to the extent that risk-assessment becomes an academic issue, especially for those patients whose only reasonable chance for either cure or palliation of unbearable disease is surgery. However, the internist's role in these situations often has preoperative, intraoperative, and postoperative ramifications. Preoperatively, the internist assesses operative risk and intervenes, when possible, to reduce the likelihood of surgical complications. Patients who clearly cannot survive surgery may be identified and channeled to other treatment modalities. Intraoperatively, the internist may be called upon to help with the management of acute organ failure, cardiac arrest, or vascular collapse. Following surgery, the internist may help by managing cardiopulmonary problems and treating infectious complications. The critical care internist is therefore an important member of the perioperative team and often provides valuable expertise, which can help to identify and treat problems expediently. PMID- 2196401 TI - Rat model for evaluating inhibitors of human renin. AB - A rat model that provides a rapid method for the in vivo evaluation of potential inhibitors of human renin has been developed and validated. Recombinant human renin was infused intravenously into anesthetized, nephrectomized, ganglion blocked rats. The resulting blood pressure had an approximate 60 mm Hg human renin-dependent component. The angiotensin I to angiotensin II converting enzyme inhibitor, captopril, and the renin inhibitor, ditekiren (U-71038), were capable of abolishing this component after oral administration. Oral administration of ditekiren to rats receiving human renin infusions evoked dose-dependent hypotensive responses that were greater in magnitude and longer in duration than those elicited in rats receiving hog renin infusions. Observations made in the renin-infused rats reflected the results of in vitro kinetic studies that had indicated a greater binding affinity of ditekiren for human renin than for hog renin. PMID- 2196402 TI - Statistical modeling of the effects of drug combinations. AB - A method is described for identifying and quantitating departures from additivity (i.e., synergism and antagonism) when drugs having like effects are given in combination. It is applicable for both graded and quantal (e.g., after probit or logit transformation) responses. Log(dose)-response curves of both drugs should be linear but need not be parallel. The following model is fitted to dose response data for both the individual drugs and combinations of drugs: Y = beta 0 + beta 1 log(A + P.B + beta 4(A.P.B)1/2) where Y is the response, A is the amount of drug A, B is the amount of drug B, and P is a relative potency of the drugs given by log(P) = beta 2 + beta 3 log(B'), in which B' is the solution to B' - B A/P = 0. If log(dose)-response curves of the two drugs are parallel, beta 3 = 0, and P becomes a constant parameter to be estimated. A positive value of beta 4 corresponds to synergism and a negative value to antagonism. Hypothesis tests may be carried out to determine whether beta 4 is significantly different from zero. PMID- 2196403 TI - The discovery and development of buspirone: a new approach to the treatment of anxiety. PMID- 2196405 TI - Synthetic immunomodulating agents. PMID- 2196404 TI - Polymethylene tetraamines: a novel class of cardioselective M2-antagonists. PMID- 2196407 TI - [The exocrine pancreas regulates food intake]. PMID- 2196406 TI - [Divided opinion on Streptococcus group A]. PMID- 2196408 TI - [The man behind the method: Christian Doppler--the man behind a revised, old established method. Doppler measurement improved diagnosis of cerebrovascular disorders]. PMID- 2196409 TI - Do severity of disease classification tools change patient care? PMID- 2196410 TI - Do objective estimates of chances for survival influence decisions to withhold or withdraw treatment? The French Multicentric Group of ICU Research. AB - The authors studied the impact on clinical decision making of providing feedback of objective prognostic information describing the probability of survival for ICU patients with multiple organ system failure (OSF). The prognostic estimates, derived from a control period (1), were to be provided on a daily basis to physicians providing treatment in 25 French ICUs during a subsequent experimental period (2). The types of, frequencies of, and reasons for decisions to limit or stop treatment in the two periods were compared. In the experimental period 2, 17 ICUs participated in the feedback study. Within these 17 units, there was a small but significant (p less than 0.05) increase in decisions to stop active treatment and provide comfort care that was limited to patients with three or more OSFs. There was no change in decision making in the eight units that did not participate in the feedback study. Although these results suggest a direct causal relationship between the provision of objective prognostic data and changes in physician decision making, the small increase in comfort care decisions (n = 14) between period 1 and period 2 and the fact that only 17 of the 25 original units participated in the feedback study make it difficult to eliminate other influences. There was no indication in this study, however, that explicit provision of prognostic data led to a sense of therapeutic futility. PMID- 2196411 TI - Judicial and legislative viewpoints on physician misestimation of patient dysutilities: a problem for decision analysts. AB - Appellate courts, state legislatures, and ethicists have recently (post-1972) been interested-through the evolving court doctrine of informed consent-in patient-physician joint decision making. Yet these professional groups' approaches differ markedly from that of decision analysis, failing to include an explicit role for patients' rational processing of information in informed consent. In addition, these groups charge that decision analysts are misestimating patient dysutilities. This paper examines three issues: 1) in what sense(s), if any, is decision-analytic work in individualized medical decision making misestimating patient dysutilities, 2) if this misestimation is real, whether it is an example of the normative-descriptive tensions that exist in medical decision making, and 3) in what ways do the relationships between decision-analytic and judicial decision making change when informed consent is viewed in terms of contract law as opposed to tort law. This paper argues that a key link dividing these professional groups is the differing weights given to the "value of information" by decision-analytic vs. non-decision-analytic frameworks. PMID- 2196412 TI - Using explicit decision rules to manage issues of justice, risk, and ethics in decision analysis: when is it not rational to maximize expected utility? AB - Concepts of justice, risk, and ethics can be merged with decision analysis by requiring the analyst to specify explicity a decision rule or sequence of rules. Decision rules are categorized by whether they consider: 1) aspects of outcome distributions beyond central tendencies; 2) probabilities as well as utilities of outcomes; and 3) means as well as ends. This formulation suggests that distribution-based decision rules could address both risk (for an individual) and justice (for the population). Rational choice under risk if choices are one-time only (vs. repeated events) or if one branch contains unlikely but disastrous outcomes might ignore probability information. Incorporating risk attitude into decision rules rather than utilities could facilitate use of multiattribute approaches to measuring outcomes. Certain ethical concerns could be addressed by prior specification of rules for allowing particular branches. Examples, including selection of polio vaccine strategies, are discussed, and theoretical and practical implications of a decision rule approach noted. PMID- 2196413 TI - Psychological androgyny and preference for intubation in a hypothetical case of end-stage lung disease. AB - Psychological androgyny theory (PAT) was employed as a model of the interpersonal (social) and task activities required of physicians for care of their patients. According to PAT, individuals with a large repertoire of task and social skills ("androgynous" individuals) should be optimally adaptable to contingencies reflecting varying combinations of task and social challenges. The authors examined the relationship between androgyny and preference for intubation on a patient management problem involving end-stage lung disease for 67 general internists and internal medicine housestaff from two hospitals. Results revealed a negative relationship between androgyny and preference for intubation, suggesting that androgynous and nonandrogynous physicians respond differently to complex and difficult decision-making tasks. Indirect evidence is offered to suggest that this response reflects a general tendency to utilize fewer health care resources. Discussion focuses on the need to improve the precision of measurement of these latent constructs. PMID- 2196414 TI - Management of intracranial aneurysms, or how to report decision analyses in clinical journals. PMID- 2196415 TI - Virulent Escherichia coli strains for chicks bind fibronectin and type II collagen. AB - 125I-fibronectin and 125I-collagen (type II) binding was detected in Escherichia coli strains isolated from chickens and poults. High fibronectin binding-strains also bind the 29 kD aminoterminal fragment of fibronectin. Binding properties in strain CK28 were partially characterized. The highest binding of 125I-fibronectin and 125I-collagen for strain CK28 was obtained with bacteria grown at 33 degrees C. Binding of 125I-fibronectin, its 125I-29 kD fragment, and 125I-collagen, was very rapid, reaching a maximum in 5 min. Binding of 125I-fibronectin and 125I collagen was considerably inhibited by preincubation of bacteria with unlabelled fibronectin and unlabelled type I collagen respectively, but not inhibited with human immunoglobulin G or bovine serum albumin. Inhibition experiments showed that the reversibility of 125I-fibronectin binding was estimated at approximately 50%, while reversibility for 125I-collagen binding was higher than 90%. Receptors for fibronectin, its 29 kD fragment, and collagen were released from the bacterial surface by treatment at different temperatures, and surface material released at 100 degrees C inhibited binding. There was cross-inhibition for both fibronectin and collagen binding when unlabelled fibronectin and unlabelled collagen were used as inhibitors, suggesting that binding receptors for both proteins may be closely located. PMID- 2196416 TI - Role of adenine nucleotides in the regulation of bacterial energy metabolism: theoretical problems and experimental pitfalls. AB - The effect of growth rate on ATP pool and adenylate energy charge (EC) value of Escherichia coli has been studied in batch culture on different media (mu max varying from 0.1 h-1 to 1.2 h-2) and in continuous culture at dilution rates (D = mu) from 0.045 h-1 to 0.310 h-1. Within the limits of error both ATP pool and EC values did not change with alterations in the relative growth rate of E. coli. The effect of in vivo EC values on experimental errors in ATP, ADP and AMP measurements with the luciferin-luciferase method, and, subsequently, on measurements of different ratios between adenylates, as in the case of adenylate kinase in vivo equilibrium, is discussed. PMID- 2196417 TI - Gonadorelin for induction of ovulation. PMID- 2196418 TI - Scientific and regulatory issues relevant to assessing risk for developmental neurotoxicity: an overview. AB - The effects of chemical exposure on the developing nervous system have been documented in both humans and animals for a variety of agents. However, the comparability of these effects has not been carefully evaluated to determine the predictability of animal models to adverse effects in humans. A workshop sponsored by the U.S. Environmental Protection Agency (EPA) and the National Institute on Drug Abuse was held on April 11-13, 1989, to address the Qualitative and Quantitative Comparability of Human and Animal Developmental Neurotoxicity. Invited experts were asked to review the human and animal data on several agents that are known to cause developmental neurotoxicity in humans, including lead, methylmercury, selected abused agents, anticonvulsants, polychlorinated biphenyls (PCBs), ethanol and X-irradiation, and to make quantitative comparisons on a specific end point basis as well as on a functional category basis. In addition, they were asked to make quantitative comparisons when adequate dose-effect data were available. The data also were evaluated in the context of the proposed EPA developmental neurotoxicity testing battery to determine whether or not the battery would adequately detect the effects of each agent. Finally, four work groups were asked to reach consensus on issues relating to: 1) comparability of end points across species for developmental neurotoxicity; 2) testing methods in developmental neurotoxicity for use in human risk assessment; 3) weight-of evidence and quantitative evaluation of data from developmental neurotoxicity studies; and 4) triggers for developmental neurotoxicity testing. PMID- 2196419 TI - Methylmercury developmental neurotoxicity: a comparison of effects in humans and animals. AB - A qualitative and quantitative comparison of the neuropathological and neurobehavioral effects of early methylmercury (MeHg) exposure is presented. The focus of the qualitative comparison is the examination of how specific end-points (and categories of behavioral functions) compare across species. The focus of the quantitative comparison is the investigation of the relationship between MeHg exposure, target-organ dose and effects in humans and animals. The results of the comparisons are discussed in the context of the adequacy of the proposed EPA neurotoxicity battery to characterize the risk of MeHg to humans. The comparisons reveal several qualitative and quantitative similarities in the neuropathological effects of MeHg on humans and animals at high levels of exposure. Reports of neuropathological effects at lower levels are available for animals only, precluding any comparison. At high levels of exposure, specific neurobehavioral end-points affected across species are also similar. Effects at lower levels of exposure are similar if categories of neurobehavioral functioning are compared. Changes in the EPA test battery consistent with the results of the comparisons are discussed. PMID- 2196420 TI - Developmental neurotoxicity of anticonvulsants: human and animal evidence on phenytoin. AB - Most epileptic women delivering children each year take anticonvulsants throughout pregnancy. The teratogenic potential of anticonvulsants is most notable for phenytoin, trimethadione, valproic acid, and carbamazepine. This review focuses on the human and animal evidence for the teratogenicity of phenytoin, with emphasis on neurobehavioral end points. The Fetal Hydantoin Syndrome (FHS) consists of craniofacial defects and any two of the following: pre/postnatal growth deficiency, limb defects, major malformations, and mental deficiency. Available data suggest a prevalence of FHS of 10-30% in infants of women ingesting 100-800 mg/kg of phenytoin during the first trimester or beyond. Unfortunately, data on neurobehavioral development in FHS children is limited. Animal models of FHS have been developed and those focusing on neurobehavioral effects are reviewed. Phenytoin produces multiple behavioral dysfunctions in rat offspring at subteratogenic and nongrowth retarding doses. These behaviorally teratogenic doses produce maternal serum phenytoin concentrations in rats comparable to those found in humans. The dysfunctions in rats are dose-dependent and exposure-period-dependent, but independent of nutritional, maternal rearing, or seizure disorder confounds. Effects include vestibular dysfunction, hyperactivity and deficits in learning and memory. General comparability between the human and animal findings for phenytoin are apparent, however, difficulties with existing studies prevent precise comparisons. Animal studies have not dealt satisfactorily with the potential contribution of epileptic disease state to the FHS, with fetal brain drug concentration determinations, a complete dose-effect range, effects in multiple species (although limited nonhuman primate data exist), site of CNS injury, and the comparability of end points assessed. Human studies have not dealt satisfactorily with issues of the need for prospective study designs, separation of the effects of different anticonvulsants, or adequate long-term follow-up of cases, especially with attention to neuropsychological assessment. PMID- 2196421 TI - The comparative developmental neurotoxicity of lead in humans and animals. AB - The effects of lead on neurobehavioral development have been extensively investigated in humans as well as animals. This valuable lode of research findings offers a basis for comparing the developmental neurobehavioral toxicity of lead across species and for assessing the validity of animal models of developmental neurotoxicity. Comparisons of human and animal findings suggest that the greatest qualitative similarities involve relatively complex behavioral processes such as cognition and learning. Quantitative comparisons based on dose response relationships for these endpoints are difficult to make because the relationships are sometimes nonmonotonic (U-shaped) and because blood lead levels may not be directly comparable between species. However, the lowest levels of exposure at which developmental neurobehavioral effects have been observed are similar: 10-15 micrograms/dl in children, less than 15 micrograms/dl in primates, and less than 20 micrograms/dl in rodents. Although the convergence between animal and human findings for other neurobehavioral endpoints is not as striking, sensory-evoked potentials and communicative processes offer two promising areas for continued investigation and cross-species comparison. PMID- 2196422 TI - Prenatal alcohol exposure: comparability of effects in humans and animal models. AB - Much is known about the potential consequences of prenatal alcohol exposure through data developed in animals and man. However, little attempt has been made to compare the human and animal literature with respect to qualitative and quantitative similarities and differences. To this end, a comparison was made between the effects reported in humans following moderate levels of alcohol exposure and the neurobehavioral effects detected using animal models. A good deal of congruence was found with respect to qualitative endpoints. General functional categories, such as deficits in learning, inhibition, attention, regulatory behaviors, and motor performance were reported to be affected in both animals and children. Quantitatively, although the dose required to produce an effect differs across species, the resultant circulating blood alcohol levels are quite similar. In addition, while compelling data are limited, the magnitude of the observed effects are generally dose-related for both humans and animals. PMID- 2196424 TI - Workshop on the qualitative and quantitative comparability of human and animal developmental neurotoxicity, Work Group II report: testing methods in developmental neurotoxicity for use in human risk assessment. AB - The Work Group addressed the design and content of a basic screening battery for detecting or flagging developmental neurotoxicity. It was agreed that a basic screening battery should be incorporated routinely into any developmental or reproductive toxicity study conducted for risk assessment purposes, and that a "triggered" stand-alone developmental neurotoxicity study, as exemplified by the current EPA proposal, should include greater in-depth evaluation of CNS function and pathology. Time constraints did not permit the group to address the design or content of such a stand-alone study. It was acknowledged unanimously that a basic screening battery may provide more information than simply the detection of neurotoxicity; however, it should not be expected to provide detailed dose response information nor to identify the precise mechanism of agent action. The Work Group also agreed that a basic screening battery should include evaluation of multiple CNS functions, that observed alterations may be indicative of primary or secondary effects on the nervous system, that the test methods selected may differ based on what is known about the agent, and that the protocol for study conduct can be as important as the methods employed. In light of these assumptions, the Work Group recommended schedules for monitoring offspring development using measures of: 1) physical landmarks, 2) brain weights, 3) neuropathology, 4) functional observations, 5) motor activity, 6) reactivity, and 7) learning and memory. The species tested, sample sizes, treatment parameters, etc., would be determined by the type of developmental or reproductive toxicity study into which the basic screening battery was incorporated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196423 TI - Ionizing radiation and the developing brain. AB - The unique susceptibility of the central nervous system to radiation exposure is attributable to its extensive period of development, the vulnerability of its neuronal cells, the migratory activity of many of its cells, its inability to replace mature neurons, and the complexity of the system itself. Radiation effects may be due to glial or neuronal cell death, interruption of migratory activity, impaired capacity to establish correct connections among cells, and/or alterations in dendritic development. These structural changes are often manifested as behavioral alterations later in life. Sensitivity to radiation (dose-response) is markedly similar among all mammalian species when developmental periods are compared. This review compares and contrasts human and animal behavioral data. Neonatal and postnatal adult behavioral tests have been shown to be sensitive, noninvasive measures of prenatal radiation exposure, although currently their predictive validity for humans is uncertain. Additional research is needed to determine the presence and significance of postnatal morphologic and functional alterations due to prenatal exposure to low levels of ionizing radiation. PMID- 2196425 TI - Workshop on the qualitative and quantitative comparability of human and animal developmental neurotoxicity, Work Group III report: weight of evidence and quantitative evaluation of developmental neurotoxicity data. AB - Work Group III discussed the qualitative and quantitative evaluation of developmental neurotoxicity data for risk assessment purposes. The Work Group concurred with the assumption that developmental neurotoxicity may result from as little as a single exposure, dependent on dose and gestational time of exposure. Maternal toxicity, during the pregnancy and/or lactational period, may confound interpretation of effects observed in the offspring, but the majority of the group agreed that if significant effects were observed in a developmental neurotoxicity study, these effects should be presumed relevant to potential risk in humans. Others in the group indicated that these effects should be designated developmental toxicity but not necessarily developmental neurotoxicity. Concurrent toxicity (in the same organism, at the same dose, etc.) was also discussed, with the same concern as with maternal toxicity, i.e., are the results observed from developmental neurotoxicity per se or from other toxicity impacting on and confounding the neurotoxicity test results. A majority of the group regarded any effect observed in a neurotoxicity test as consistent with developmental neurotoxicity. The minority reserved this designation only for neurotoxic results observed at the lowest adverse effect level and in the absence of other developmental toxicity. Discussion on weighting tests in the battery focussed on apical tests which require the most integrated functions with the caveat for confounding effects from other toxicities. Developmental neurotoxicity data were viewed as potentially useful in establishing a reference dose. The interpretation of statistically significant findings was discussed with caveats for Type I errors, consistency, biological plausibility of findings, and the concern that current draft guidelines and test rules require adult toxicity with the risk of confounding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196427 TI - Workshop on the qualitative and quantitative comparability of human and animal developmental neurotoxicity: summary and implications. AB - The Workshop on the Qualitative and Quantitative Comparability of Human and Animal Developmental Neurotoxicity was convened by the U.S. Environmental Protection Agency (EPA) and the National Institute on Drug Abuse to address issues related to when testing should be required, what test methodologies should be required, and how the data should be interpreted and applied to the risk assessment process. The background material for Work Group discussions included presentations made at the Workshop by invited experts summarizing qualitative and quantitative human and experimental animal data on specific chemicals or classes of chemicals and EPA's proposed developmental neurotoxicity testing protocol. This overview: 1) summarizes the qualitative comparisons presented at the Workshop and attempts to make some quantitative comparisons of findings across mammalian species following exposure to developmental neurotoxicants, 2) brings the common themes that were discussed among the Work Groups together into a regulatory perspective, 3) provides a status report on EPA's developmental neurotoxicity protocol, and 4) identifies research needs in the development of test methodologies and improvement of risk assessments for developmental neurotoxicants. PMID- 2196426 TI - Workshop on the qualitative and quantitative comparability of human and animal developmental neurotoxicity, Work Group IV report: triggers for developmental neurotoxicity testing. AB - A Work Group was formed to evaluate the criteria considered important in determining when to require developmental neurotoxicity testing in animal studies (i.e., triggers for testing). The primary objective of the Work Group was to determine whether there is sufficient scientific evidence to support the triggers identified by the Environmental Protection Agency and determine whether there is sufficient evidence to use structure activity relationships (SAR) to trigger automatic testing of certain classes of chemicals. A weight of evidence (WOE) approach was recommended by the Work Group in order to assist in determining which agents should undergo developmental neurotoxicity testing and to what level of testing. Evaluation of biological effects, length and duration of exposure, and quality and quantity of data available on an agent should be used in the WOE approach. Agents that are teratogenic to the central nervous system (CNS) were considered of highest priority for developmental neurotoxicity testing, especially if there is the potential for a high degree of exposure. Neuropathic and neuroactive compounds, chemicals with hormone-like activity, and developmental toxicants (with effects other than structural abnormalities of the CNS) were also considered likely candidates for such testing. Although reluctant to recommend testing based solely on SAR or chemical class, the Work Group recognized the importance of considering SAR along with other toxicity data, pharmacokinetic data and potential human exposure in making final requirements or recommendations for further testing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196428 TI - Gene fliA encodes an alternative sigma factor specific for flagellar operons in Salmonella typhimurium. AB - Through genetic studies, the fliA gene product has been shown to regulate positively gene expression in late operons of the flagellar regulon in Salmonella typhimurium. In the present study, the fliA gene was cloned and sequenced. The fliA coding region consisted of 717 nucleotides beginning with the GTG initiation codon and the conserved sequence specific to promoters for flagellar operons was found to exist upstream of the coding region. The fliA gene product deduced from the nucleotide sequence was a protein with 239 amino acid residues and the calculated molecular mass was 27,470 dalton. The deduced amino acid sequence was homologous with that of sigma 28, a flagellar specific sigma factor of Bacillus subtilis. The fliA gene product was identified as a protein of molecular mass 29 kDa in the in vitro transcription-translation system, while three proteins of 29 kDa, 31 kDa and 32 kDa were found in the products programmed by the fliA gene in minicells and in maxicells. The 29 kDa FliA protein was purified from the FliA overproducing strain which carried the ptac-fliA fusion. This protein activated the in vitro synthesis of flagellin, the fliC gene product. RNA polymerase containing the purified FliA protein was shown to transcribe the fliC gene. These results indicate that FliA protein functions as an alternative sigma factor specific for S. typhimurium flagellar operons. PMID- 2196429 TI - Cotranscription of the wild-type chloroplast atpE gene encoding the CF1/CF0 epsilon subunit with the 3' half of the rps7 gene in Chlamydomonas reinhardtii and characterization of frameshift mutations in atpE. AB - We have characterized two independently isolated point mutants in Chlamydomonas reinhardtii, ac-u-a-1-15 and FUD 17, mapping to the chloroplast ac-u-a locus which corresponds to the atpE gene. Both mutants have a single A:T base pair deletion in a sequence of 6 A:T base pairs at nucleotide positions 102 to 107. This causes a frameshift, altering the coding sequence for the next 8 amino acids and creating a termination codon at amino acid position 44, 98 amino acids from the C-terminus of the protein. Assembly of the ATP synthase is impaired in the mutants; less than 5% of the wild-type level of alpha and beta subunits and no gamma or epsilon subunits are associated with thylakoid membranes of the mutants. The genes encoding the beta and epsilon subunits of the chloroplast ATP synthase from C. reinhardtii are not cotranscribed, in contrast to all other photosynthetic organisms examined to date. Four transcripts, of approximately 1.7, 2.9, 3.3 and 7.0 x 10(3) nucleotides (nt), are found for the atpE gene. S1 nuclease mapping of the 1.7 x 10(3) nt transcript shows that the atpE gene message is preceded by a leader of about 1250 nt. DNA sequence analysis of this region revealed a 159 bp open reading frame corresponding to the 3' half of the rps7 gene, encoding the S7 protein of the small subunit of the chloroplast ribosome. Only the 5' portion of this gene is located in the opposite unique sequence region of the C. reinhardtii chloroplast genome where the rps7 gene was previously mapped by heterologous hybridization. PMID- 2196430 TI - Initiation of meiosis and sporulation in Saccharomyces cerevisiae requires a novel protein kinase homologue. AB - SME1 was cloned due to its high copy number effect: it enabled MATa/MAT alpha diploid cells to undergo meiosis and sporulation in a vegetative medium. Disruption of SME1 resulted in a recessive Spo- phenotype. These results suggest that SME1 is a positive regulator for meiosis. DNA sequencing analysis revealed an open reading frame of 645 amino acids. An amino terminal peptide of ca 400 amino acids in the deduced protein was similar to known protein kinases. Transcription of SME1 was regulated negatively by nitrogen and glucose and positively by MATa/MAT alpha and IME1, another positive regulator gene of meiosis. By complementation analysis, SME1 was found to be identical to IME2, which had been shown to be important in meiosis. These results suggest that IME1 product stimulates meiosis by activating transcription of SME1 (IME2) and that protein phosphorylation is required for initiation of meiosis. PMID- 2196431 TI - Isolation and nucleotide sequence of an autonomously replicating sequence (ARS) element functional in Candida albicans and Saccharomyces cerevisiae. AB - An 8.6-kb fragment was isolated from an EcoRI digest of Candida albicans ATCC 10261 genomic DNA which conferred the property of autonomous replication in Saccharomyces cervisiae on the otherwise non-replicative plasmid pMK155 (5.6 kb). The DNA responsible for the replicative function was subcloned as a 1.2-kb fragment onto a non-replicative plasmid (pRC3915) containing the C. albicans URA3 and LEU2 genes to form plasmid pRC3920. This plasmid was capable of autonomous replication in both S. cerevisiae and C. albicans and transformed S. cerevisiae AH22 (leu2-) to Leu+ at a frequency of 2.15 x 10(3) transformants per microgram DNA, and transformed C. albicans SGY-243 (delta ura3) to Ura+ at a frequency of 1.91 x 10(3) transformants per microgram DNA. Sequence analysis of the cloned DNA revealed the presence of two identical regions of eleven base pairs (5'TTTTATGTTTT3') which agreed with the consensus of autonomously replicating sequence (ARS) cores functional in S. cerevisiae. In addition there were two 10/11 and numerous 9/11 matches to the core consensus. The two 11/11 matches to the consensus, CaARS1 and CaARS2, were located on opposite strands in a non coding AT-rich region and were separated by 107 bp. Also present on the C. albicans DNA, 538 bp from the ARS cores, was a gene for 5S rRNA which showed sequence homology with several other yeast 5S rRNA genes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196432 TI - Effect of enhanced synthesis of the epsilon subunit of DNA polymerase III on spontaneous and UV-induced mutagenesis of the Escherichia coli glyU gene. AB - We have studied spontaneous and UV mutagenesis of the glyU gene in Escherichia coli trpA461 (GAG) strains carrying the pIP11 plasmid, in which the dnaQ gene encoding the 3'-5' exonuclease subunit (epsilon) of DNA polymerase III is fused to the tac(trp-lac) promoter. We have used a pair of M13glyU phage in which the gene encoding the glycyl-tRNA is cloned in opposite orientations, consequently the phage present either GGG or CCC anticodon triplets for mutagenesis. The presence of IPTG, the inducer of the tac-dnaQ fusion, results in about 100-fold decrease in frequency of spontaneous Su+ (GAG) mutations arising in the CCC phage. The enhanced expression of tac-dnaQ reduces 10-fold the frequency of UV induced Su+ (GAG) mutations in the CCC phage and nearly completely prevents generation by UV of Su+ (GAG) mutations in the GGG phage, in which UV-induced pyrimidine photo-products can be formed only in the vicinity of the target triplet. These results suggest that both locally and regionally targeted mutagenesis is affected by overproduction of the epsilon subunit. By delayed photoreversal mutagenesis we have shown that UV-induced chromosomal mutagenesis of the umuC36 trpA461 strain harboring pIP11 is completely abolished in the presence of IPTG. This result seems to indicate that the misinocorporation step of DNA translesion synthesis is affected by excess of the epsilon subunit. Finally, we have introduced the pIP13 plasmid carrying the dnaQ gene into the recA1207 strain, which is deficient in the recombinase activity of RecA but constitutive in the protease activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196433 TI - Construction of an integration vector for use in the archaebacterium Methanococcus voltae and expression of a eubacterial resistance gene. AB - An integration vector for use in Methanococcus voltae was constructed, based on the Escherichia coli vector pUC18. It carries the structural gene for puromycin transacetylase from Streptomyces alboniger, which is flanked by expression signals of M. voltae structural genes and hisA gene sequences of this bacterium. Transformed M. voltae cells are puromycin resistant. Several types of integration of the vector into the chromosome were found. Only one case was due to nonhomologous recombination. The integrated sequences were stable under selective pressure but were slowly lost in some cases in the absence of the selective drug. The vector could be excised from M. voltae chromosomal DNA, recircularized and transformed back into E. coli. PMID- 2196434 TI - Yeast telomere length varies in response to changes in the amount of polyC1-3A in the cell. AB - Yeast chromosomes terminate in a GC-rich tail of DNA. Previous investigations have shown that the length of this tail can change in response to genetic variation. Here we present data that show that the length can also alter in response to changes in the amount of the GC-rich DNA found elsewhere in the nucleus. PMID- 2196435 TI - Chromosome replication pattern in dam mutants of Escherichia coli. AB - The replication cycle of Escherichia coli dam mutants was analysed and compared with that of isogenic Dam+ strains. Marker frequency analyses indicated no gross difference between the strains. In the Dam- as well as in the Dam+ bacteria, initiation most likely occurs at oriC, replication forks move at a constant and invariant velocity, and termination takes place in the terC region. An analysis of replication terminator activity indicated that this activity is unaffected by the methylation status. Taken together with previous results, our data are compatible with Dam methylation controlling initiation timing but no subsequent step of the replication process. PMID- 2196436 TI - Pharmacological and molecular evidence that the contractile response to serotonin in rat stomach fundus is not mediated by activation of the 5-hydroxytryptamine1C receptor. AB - The receptor mediating contraction in response to serotonin in the rat stomach fundus has not been characterized in light of the currently acceptable serotonergic receptor classification scheme. Several biochemical and pharmacological approaches to a characterization of this receptor have demonstrated nonidentity with the 5-hydroxytryptamine2 (5HT2), 5HT3, 5HT1A, and 5HT1B receptors, as defined by radiolabeled ligand binding studies in brain cortical membranes. Although there have been reports suggesting that the receptor in the rat stomach fundus may be analogous to the 5HT1C receptor, other pharmacological and biochemical studies have not been consistent with this idea. The present study utilized high affinity ligands for the 5HT1C receptor and the recently derived 5HT1C receptor cDNA clone to provide a more definitive approach to the examination of the relationship between the 5HT1C receptor and the serotonergic contractile receptor in the rat stomach fundus. Using three ligands with high affinity at the 5HT1C receptor, LY53857, ritanserin, and SCH23390, the contractile response to serotonin was inhibited by all three ligands. However, inhibition did not appear competitive nor was the inhibitory potency of these ligands consistent with their affinity at 5HT1C binding sites in brain cortical membranes. We further showed that SCH23390, unlike LY53857 and ritanserin, was also a partial agonist, producing a maximal contraction that was approximately 50% of the maximal response to serotonin in the rat stomach fundus. Thus, the use of these ligands did not support the contention that the receptor mediating serotonin-induced contractions in the rat stomach is identical to the 5HT1C receptor. In more definitive studies using a 5HT1C receptor cDNA probe, we were unable to detect hybridization of the probe with any mRNA species from the rat stomach fundus, whereas the 5HT1C receptor cDNA probe did hybridize to the 5HT1C receptor mRNA in rat brain. Because the cathepsin-D cDNA probe hybridized equally in rat brain and stomach fundus, ensuring the integrity of the RNA preparation from both tissues, the absence of measurable quantities of the 5HT1C receptor mRNA in the rat stomach was probe specific and not an artifact. Furthermore, primers specific for the rat 5HT1C receptor sequence did not detect significant levels of receptor mRNA in rat fundus, although the target sequence was amplified a minimum of 10(5)-fold in a polymerase chain reaction. These studies do not support the contention that the receptor mediating contractile responses to serotonin in the rat stomach fundus is identical to the 5HT1C receptor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2196437 TI - Yeast and human TATA-binding proteins have nearly identical DNA sequence requirements for transcription in vitro. AB - We have analyzed the DNA sequence requirements for TATA element function by assaying the transcriptional activities of 25 promoters, including those representing each of the 18 single-point mutants of the consensus sequence TATAAA, in a reconstituted in vitro system that depends on the TATA element binding factor TFIID. Interestingly, yeast TFIID and HeLa cell TFIID were virtually identical in terms of their relative activities on this set of promoters. Of the mutated elements, only two had undetectable activity; the rest had activities ranging from 2 to 75% of the activity of the consensus element, which was the most active. In addition, mutations of the nucleotide following the TATAAA core strongly influenced transcriptional activity, although with somewhat different effects on yeast and HeLa TFIID. The activities of all these promoters depended upon TFIID, and the level of TFIID-dependent transcription in vitro correlated strongly with their activities in yeast cells. This suggests that the in vivo activities of these elements reflect their ability to functionally interact with a single TATA-binding factor. However, some elements with similar activities in vitro supported very different levels of transcriptional activation by GAL4 protein in vivo. These results extend the degree of evolutionary conservation between yeast and mammalian TFIID and are useful for predicting the level of TATA element function from the primary sequence. PMID- 2196438 TI - Adenylate cyclase in Saccharomyces cerevisiae is a peripheral membrane protein. AB - The adenylate cyclase system of the yeast Saccharomyces cerevisiae contains the CYR1 polypeptide, responsible for catalyzing formation of cyclic AMP (cAMP) from ATP, and two RAS polypeptides, which mediate stimulation of cAMP synthesis of guanine nucleotides. By analogy to the mammalian enzyme, models of yeast adenylate cyclase have depicted the enzyme as a membrane protein. We have concluded that adenylate cyclase is only peripherally bound to the yeast membrane, based on the following criteria: (i) substantial activity was found in cytoplasmic fractions; (ii) activity was released from membranes by the addition of 0.5 M NaCl; (iii) in the presence of 0.5 M NaCl, activity in detergent extracts had hydrodynamic properties identical to those of cytosolic or NaCl extracted enzyme; (iv) antibodies to yeast adenylate cyclase identified a full length adenylate cyclase in both membrane and cytosol fractions; and (v) activity from both cytosolic fractions and NaCl extracts could be functionally reconstituted into membranes lacking adenylate cyclase activity. The binding of adenylate cyclase to the membrane may have regulatory significance; the fraction of activity associated with the membrane increased as cultures approached stationary phase. In addition, binding of adenylate cyclase to membranes appeared to be inhibited by cAMP. These results indicate the existence of a protein anchoring adenylate cyclase to the membrane. The identity of this protein remains unknown. PMID- 2196439 TI - Mutational analysis of the consensus sequence of a replication origin from yeast chromosome III. AB - Yeast autonomously replicating sequence (ARS) elements contain an 11-base-pair core consensus sequence (5'-[A/T]TTTAT[A/G]TTT[A/T]-3') that is required for function. The contribution of each position within this sequence to ARS activity was tested by creating all possible single-base mutations within the core consensus sequence of ARS307 (formerly called the C2G1 ARS) and testing their effects on high-frequency transformation and on plasmid stability. Of the 33 mutations, 22 abolished ARS function as measured by high-frequency transformation, 7 caused more than twofold reductions in plasmid stability, and 4 had no effect on plasmid stability. Mutations that reduced or abolished ARS activity occurred at each position in the consensus sequence, demonstrating that each position of this sequence contributes to ARS function. Of the four mutations that had no effect on ARS activity, three created alternative perfect matches to the core consensus sequence, demonstrating that the alternate bases allowed by the consensus sequence are, indeed, interchangeable. In addition, a change from T to C at position 6 did not perturb wild-type efficiency. To test whether the essential region extends beyond the 11-base-pair consensus sequence, the effects on plasmid stability of point mutations one base 3' to the T-rich strand of the core consensus sequence (position 12) and deletion mutations that altered bases 5' to the T-rich strand of the core consensus sequence were examined. An A at position 12 or the removal of three T residues 5' to the core consensus sequence severely diminished ARS efficiency, showing that the region required for full ARS efficiency extends beyond the core consensus sequence in both directions. PMID- 2196440 TI - Enhanced translation and increased turnover of c-myc proteins occur during differentiation of murine erythroleukemia cells. AB - To determine whether regulation of c-myc proteins occurs during the differentiation of murine erythroleukemia cells, we examined c-myc protein synthesis and accumulation throughout dimethyl sulfoxide (DMSO)- or hypoxanthine induced differentiation. c-myc protein expression exhibited an overall biphasic reduction, with an initial concomitant decrease in c-myc RNA, protein synthesis, and protein accumulation early during the commitment phase. However, as the mRNA and protein levels recovered, c-myc protein synthesis levels dissociated from the levels of c-myc mRNA and protein accumulation. This dissociation appears to result from unusual translational and posttranslational regulation during differentiation. Translational enhancement was suggested by the observation that relatively high levels of c-myc proteins were synthesized from relatively moderate levels of c-myc RNA. This translational enhancement was not observed with c-myb. Under certain culture conditions, we also observed a change in the relative synthesis ratio of the two independently initiated c-myc proteins. Posttranslational regulation was evidenced by a dramatic postcommitment decrease in the accumulated c-myc protein levels despite relatively high levels of c-myc protein synthesis. This decrease corresponded with a twofold increase in the turnover of c-myc proteins. The consequence of this regulation was that the most substantial decrease in c-myc protein accumulation occurred during the postcommitment phase of differentiation. This result supports the hypothesis that the reduction in c-myc at relatively late times is most important for completion of murine erythroleukemia cell terminal differentiation. PMID- 2196441 TI - The cytokine response element of the rat alpha 1-acid glycoprotein gene is a complex of several interacting regulatory sequences. AB - Expression of the rat alpha 1-acid glycoprotein gene is stimulated by interleukin 1 (IL-1) and interleukin-6 (IL-6) and is synergistically enhanced by the combination of the two. The distal regulatory element (DRE), a 142-base-pair (bp) sequence located 5 kilobase pairs upstream of the transcriptional start site, appears to be crucial for this cytokine response. The cytokine-specific regulatory sequences within the DRE have been identified by inserting individual DRE subregions, selected combinations of these, or a few linker mutated fragments into a plasmid containing an enhancerless simian virus 40 promoter linked to the chloramphenicol acetyltransferase gene. The regulatory activity was determined in transiently transfected human and rat hepatoma cells. The IL-1 response region was confined to the 5'-most 62 bp of the DRE, and its function seemed to depend on at least two separate components. The same region was also responsive to phorbol ester treatment. The IL-6 regulatory function was dependent on a 54-bp sequence located within the 3' half of the DRE. When the IL-1 response region was recombined with the IL-6 regulatory region of the DRE or with IL-6 response elements of other plasma protein genes, a strong cooperative action by IL-1 and IL-6 was achieved. The functional DRE sequences were recognized by nuclear proteins extracted from rat liver and hepatoma cells. However, no cytokine inducible binding activity was detectable, which suggests that transcriptional regulation through the DRE might be controlled by posttranslational modification of constitutively bound trans-acting factors. PMID- 2196442 TI - Identification and characterization of the poly(A)-binding proteins from the sea urchin: a quantitative analysis. AB - Poly(A)-binding proteins (PABPs) are the best characterized messenger RNA-binding proteins of eucaryotic cells and have been identified in diverse organisms such as mammals and yeasts. The in vitro poly(A)-binding properties of these proteins have been studied intensively; however, little is known about their function in cells. In this report, we show that sea urchin eggs have two molecular weight forms of PABP (molecular weights of 66,000 and 80,000). Each of these has at least five posttranslationally modified forms. Both sea urchin PABPs are found in approximately 1:1 ratios in both cytoplasmic and nuclear fractions of embryonic cells. Quantification in eggs and embryos revealed that sea urchin PABPs are surprisingly abundant, composing about 0.6% of total cellular protein. This is 50 times more than required to bind all the poly(A) in the egg based on the binding stoichiometry of 1 PABP per 27 adenosine residues. We found that density gradient centrifugation strips PABP from poly(A) and therefore underestimates the amount of PABP complexed to poly(A)+ RNA in cell homogenates. However, large-pore gel filtration chromatography could be used to separate intact poly(A)-PABP complexes from free PABP. Using the gel filtration method, we found that the threefold increase in poly(A) content of the egg after fertilization is paralleled by an approximate fivefold increase in the amount of bound PABP. Furthermore, both translated and nontranslated poly(A)+ RNAs appear to be complexed to PABP. As expected from the observation that PABPs are so abundant, greater than 95% of the PABP of the cell is uncomplexed protein. PMID- 2196443 TI - Epidermal growth factor receptor, but not c-erbB-2, activation prevents lactogenic hormone induction of the beta-casein gene in mouse mammary epithelial cells. AB - The HC11 cell line was isolated from mammary gland cells of pregnant mice. The cells displayed a normal phenotype and retained some characteristics of mammary epithelial cell differentiation. After treatment with the lactogenic hormones prolactin and glucocorticoids, the HC11 cells expressed the milk protein beta casein. Various oncogenes were transfected and expressed in HC11 cells. The oncogenes were tested for their transformation ability and for their effects upon the differentiation of the HC11 cells. All of the oncogenes tested, including activated human Ha-ras, human transforming growth factor-alpha, activated rat neuT, and human c-erbB-2 activated by a point mutation in the transmembrane domain, caused transformation of the HC11 cells, as shown by tumor formation in nude mice. HC11 cells expressing the neuT and activated c-erbB-2 genes synthesized beta-casein in response to lactogenic hormones, whereas those expressing the Ha-ras or transforming growth factor-alpha oncogenes were no longer able to respond to the lactogenic hormones. This inhibition of beta-casein production occurs at the transcriptional level and in the transforming growth factor-alpha-transformed cells is due to an autocrine mechanism involving the activation of the epidermal growth factor receptor. This suggests that, although the c-erbB-2 and epidermal growth factor receptors are structurally quite similar, their activation has different effects upon mammary epithelial cell differentiation. PMID- 2196444 TI - Regulation of the Discoidin I gamma gene in Dictyostelium discoideum: identification of individual promoter elements mediating induction of transcription and repression by cyclic AMP. AB - We dissected the promoter of the developmentally induced and cyclic AMP-repressed discoidin I gamma gene and identified a sequence element essential for developmental induction. Transfer of the element to an inactive heterologous promoter demonstrated that this sequence is sufficient to confer expression in axenically growing cells and to induce gene activity in development after growth on bacteria. A 16-base-pair sequence within this element was shown to be sufficient for induction in the discoidin promoter context and was used to reactivate different truncated promoter constructs. This led to the localization of an element necessary for down regulation of gene expression by extracellular cyclic AMP. PMID- 2196445 TI - Isolation, sequencing, and disruption of the yeast CKA2 gene: casein kinase II is essential for viability in Saccharomyces cerevisiae. AB - Casein kinase II of Saccharomyces cerevisiae contains two distinct catalytic subunits, alpha and alpha', which are encoded by the CKA1 and CKA2 genes, respectively. Null mutations in the CKA1 gene do not confer a detectable phenotype (J. L.-P. Chen-Wu, R. Padmanabha, and C. V. C. Glover, Mol. Cell. Biol. 8:4981-4990, 1988), presumably because of the presence of the CKA2 gene. We report here the cloning, sequencing, and disruption of the CKA2 gene. The alpha' subunit encoded by the CKA2 gene is 60% identical to the CKA1-encoded alpha subunit and 55% identical to the Drosophila alpha subunit (A. Saxena, R. Padmanabha, and C. V. C. Glover, Mol. Cell. Biol. 7:3409-3417, 1987). Deletions of the CKA2 gene were constructed by gene replacement techniques. Haploid cells in which the CKA2 gene alone is disrupted show no detectable phenotype, but haploid cells carrying disruptions in both the CKA1 and CKA2 genes are inviable. Cells in which casein kinase II activity is depleted increase substantially in size prior to growth arrest, and a significant fraction of the arrested cells exhibit a pseudomycelial morphology. Disruption of the activity also results in flocculation. Yeast strains lacking both endogenous catalytic subunit genes can be rescued by expression of the alpha and beta subunits of Drosophila casein kinase II or by expression of the Drosophila alpha subunit alone, suggesting that casein kinase II function has been conserved through evolution. PMID- 2196446 TI - A transcription factor interacting with the class I gene enhancer is inactive in tumorigenic cell lines which suppress major histocompatibility complex class I genes. AB - AKR leukemias display different amounts of major histocompatibility complex class I antigens on the cell surface. The absence of H-2Kk molecules correlates with the ability of these cell lines to form tumors in vivo as well as to escape lysis by cytotoxic T lymphocytes in vitro. In this report it is shown that the 5' regulatory area of the H-2Kk gene failed to activate transcription in H-2Kk negative cells. Examination of the proteins interacting with the H-2Kk enhancer in expressing and nonexpressing cells revealed clear differences. In particular, the level of a nuclear protein interacting at position -166 was greatly reduced in the negative cell lines. A transcription factor, known as H2TF1 or KBF1, has been shown previously to interact with this binding site and to be essential for the expression of certain class I genes as well as the expression of beta 2 microglobulin. These results demonstrate that the molecular mechanism of class I gene suppression in malignant tumor cells is at the level of transcription and is most probably modulated by H2TF1/KBFI. In addition, it is shown that the same transcription factor is only present in mouse tissues expressing class I antigens. PMID- 2196447 TI - Structure and molecular analysis of RGR1, a gene required for glucose repression of Saccharomyces cerevisiae. AB - An RGR1 gene product is required to repress expression of glucose-regulated genes in Saccharomyces cerevisiae. The abnormal morphology of rgr1 cells was studied. Scanning and transmission electron microscopic observations revealed that the cell wall of the daughter cell remained attached to that of mother cell. We cloned the RGR1 gene by complementation and showed that the cloned DNA was tightly linked to the chromosomal RGR1 locus. The cloned RGR1 gene suppressed all of the phenotypes caused by the mutation and encoded a 3.6-kilobase poly(A)+ RNA. The RGR1 gene is located on chromosome XII, as determined by pulsed-field gel electrophoresis, and we mapped rgr1 between gal2 and pep3 by genetic analysis. rgr1 was shown to be a new locus. We also determined the nucleotide sequence of RGR1, which was predicted to encode a 123-kilodalton protein. The null mutation resulted in lethality, indicating that the RGR1 gene is essential for growth. On the other hand, a carboxy-terminal deletion of the gene caused phenotypes similar to but more severe than those caused by the original mutation. The amount of reserve carbohydrates was reduced in rgr1 cells. Possible functions of the RGR1 product are discussed. PMID- 2196448 TI - Function of two discrete regions is required for nuclear localization of polymerase basic protein 1 of A/WSN/33 influenza virus (H1 N1). AB - Polymerase basic protein 1 (PB1) of influenza virus (A/WSN/33), when expressed from cloned cDNA in the absence of other viral proteins, accumulates in the nucleus. We have examined the location and nature of the nuclear localization signal of PB1 by using deletion mutants and chimeric constructions with chicken muscle pyruvate kinase, a cytoplasmic protein. Our studies showed some novel features of the nuclear localization signal of PB1. The signal was present internally within residues 180 to 252 of PB1. Moreover, unlike most nuclear localization signals, it was not a single stretch of contiguous amino acids. Instead, it possessed two discontinuous regions separated by an intervening sequence which could be deleted without affecting its nuclear localization property. On the other hand, deletion of either of the two signal regions rendered the protein cytoplasmic, indicating that the function of both regions is required for nuclear localization and that one region alone is not sufficient. Both of these signal regions contained short stretches of basic residues. Possible ways by which this novel bipartite signal can function in nuclear localization are discussed. PMID- 2196449 TI - Modification and transfer into an embryonal carcinoma cell line of a 360-kilobase human-derived yeast artificial chromosome. AB - A neomycin resistance cassette was integrated into the human-derived insert of a 360-kilobase yeast artificial chromosome (YAC) by targeting homologous recombination to Alu repeat sequences. The modified YAC was transferred into an embryonal carcinoma cell line by using polyethylene glycol-mediated spheroplast fusion. A single copy of the human sequence was introduced intact and stably maintained in the absence of selection for over 40 generations. A substantial portion of the yeast genome was retained in hybrids in addition to the YAC. Hybrid cells containing the YAC retained the ability to differentiate when treated with retinoic acid. This approach provides a powerful tool for in vitro analysis because it can be used to modify any human DNA cloned as a YAC and to transfer large fragments of DNA intact into cultured mammalian cells, thereby facilitating functional studies of genes in the context of extensive flanking DNA sequences. PMID- 2196451 TI - Complementation by BCL2 and C-HA-RAS oncogenes in malignant transformation of rat embryo fibroblasts. AB - The BCL2 (B cell lymphoma/leukemia-2) and C-HA-RAS oncogenes encode membrane associated proteins of 26 and 21 kilodaltons, respectively. Although RAS proteins have long been known for their ability to bind and hydrolyze GTP, recent investigations suggest that BCL2 encodes a novel GTP-binding protein (S. Haldar, C. Beatty, Y. Tsujimoto, and C. M. Croce, Nature [London] 342:195-198, 1989). Cotransfection of BCL2 and HA-RAS oncogenes resulted in morphological transformation of early-passage rodent fibroblasts, rendering these cells tumorigenic in animals and enabling them to grow in semisolid medium. In contrast, cotransfection of BCL2 with oncogenes that encode nuclear proteins (E1A and C-MYC) did not produce malignant transformation, whereas HA-RAS did complement with these genes. These findings suggest that proteins encoded by oncogenes such as BCL2 and HA-RAS, although having similar subcellular locations and perhaps similar biochemical properties, can regulate distinct complementary pathways involved in cellular transformation. PMID- 2196450 TI - A nucleosome-positioning sequence is required for GCN4 to activate transcription in the absence of a TATA element. AB - In the gal-his3 hybrid promoter his3-GG1, the yeast upstream activator protein GCN4 stimulates transcription when bound at the position normally occupied by the TATA element. This TATA-independent activation by GCN4 requires two additional elements in the gal enhancer region that are distinct from those involved in normal galactose induction. Both additional elements appear to be functionally distinct from a classical TATA element because they cannot be replaced by the TFIID-binding sequence TATAAA. One of these elements, termed Q, is essential for GCN4-activated transcription and contains the sequence GTCAC CCG, which overlaps (but is distinct from) a GAL4 binding site. Surprisingly, relatively small increases in the distance between Q and the GCN4 binding site significantly reduce the level of transcription. The Q element specifically interacts with a yeast protein (Q-binding protein [QBP]) that may be equivalent to Y, a protein that binds at a sequence that forms a constraint to nucleosome positioning. Analysis of various deletion mutants indicates that the sequence requirements for binding by QBP in vitro are indistinguishable from those necessary for Q activity in vivo, strongly suggesting that QBP is required for the function of this TATA independent promoter. These results support the view that transcriptional activation can occur by an alternative mechanism in which the TATA-binding factor TFIID either is not required or is not directly bound to DNA. In addition, they suggest a potential role of nucleosome positioning for the activity of a promoter. PMID- 2196452 TI - Translational activation of GCN4 mRNA in a cell-free system is triggered by uncharged tRNAs. AB - Translation of GCN4 mRNA is activated when yeast cells are grown under conditions of amino acid limitation. In this study, we established the conditions through which translation of the GCN4 mRNA could be activated in a homologous in vitro system. This activation paralleled the in vivo situation: it required the small open reading frames located in the 5' untranslated region of the GCN4 mRNA, and it was coupled with reduced rates of 43S preinitiation complex formation. Translational derepression in vitro was triggered by uncharged tRNA molecules, demonstrating that deacylated tRNAs are more proximal signals for translational activation of the GCN4 mRNA. PMID- 2196453 TI - Sequencing of Saccharomyces telomeres cloned using T4 DNA polymerase reveals two domains. AB - By using T4 DNA polymerase rather than S1 or Bal31 nuclease to clone yeast telomeres, very little telomeric DNA is lost. These clones were used to determine the DNA sequence of virtually the entire telomeric tract. Our results demonstrated that a slightly modified version, C2-3A(CA)1-6, of the consensus derived from sequence analysis of more-internal regions (J. Shampay, J. W. Szostak, and E. H. Blackburn, Nature [London] 310:154-157, 1984) extends to the very end of the chromosome. The sequence analysis also suggests that yeast telomeres consist of two domains: the proximal 120 to 150 base pairs, which appear to be protected from processes such as recombination, degradation, and elongation, and the distal portion of the telomere, which is more susceptible to these events. PMID- 2196454 TI - Meiotic recombination between dispersed repeated genes is associated with heteroduplex formation. AB - In Saccharomyces cerevisiae, recombination events occurring between allelic genes located on homologous chromosomes are often associated with heteroduplex formation. We found that recombination events between repeated genes on nonhomologous chromosomes (ectopic events) are also associated with the formation of heteroduplexes, indicating that classical and ectopic recombination events involve similar mechanisms. PMID- 2196455 TI - Induction of c-Ha-ras gene expression by double-stranded RNA and interferon requirement. AB - The addition of double-stranded RNA (dsRNA) to NIH 3T3 cells led to an increase in the RNA levels of c-Ha-ras. The double-stranded configuration was required for the increase in c-Ha-ras mRNA levels, as heat-denatured dsRNA and single-stranded RNA did not have any effect. Nuclear run-on transcription experiments indicated that the increase in c-Ha-ras mRNA levels stimulated by dsRNA was due to transcriptional activation of the gene. The induction of c-Ha-ras gene expression by dsRNA was inhibited by anti-beta interferon antibodies, suggesting that interferon might mediate the induction. PMID- 2196456 TI - Psychosocial aspects of human immunodeficiency virus infection. AB - Infection with the human immunodeficiency virus (HIV) affects not only the physiological integrity of an individual but their psychological as well. The psychosocial aspects of HIV infection are varied and may be manifested in different behaviors and emotions specific to the stage of infection. These psychosocial aspects of HIV infection are explored using its chronology as a conceptual framework. An overview of issues pertinent to the asymptomatic, acquired immunodeficiency syndrome (AIDS)-related complex and AIDS client is given with suggestions for clinical management. PMID- 2196457 TI - Recent advances in detection of human T-cell leukemia viruses type I and type II infection. AB - The human T-cell leukemia viruses type I (HTLV-I) and type II (HTLV-II) have been implicated in the pathogenesis of a variety of neoplastic and neurological disorders. Classical techniques for detection involve assay of serum for antibodies by Western blotting or ELISA, which do not discriminate between infection with HTLV-I and HTLV-II. In order to provide appropriate prognostic information to infected individuals and to obtain an accurate assessment of the prevalence of both retroviruses in the United States, we and others have applied the technique of enzymatic DNA amplification to detect HTLV-I and HTLV-II. These techniques allow rapid detection of viral nucleic acids in freshly isolated peripheral blood samples. Recent studies indicate an unusually high rate of HTLV II infection among seropositive individuals in a sampling of New Orleans intravenous drug users, indicating a need for combined serological and molecular genetic screening of high-risk populations. PMID- 2196458 TI - Prospects of AIDS therapy by thymic humoral factor, a thymic hormone. AB - Research performed in our laboratory has established that thymic humoral factor (THF), a peptide hormone isolated from calf thymus, leads to clonal expansion, differentiation and maturation of T-cell lymphocytes. THF augments the response to T-cell lectins, mixed lymphocyte reactions, graft-versus-host reactivity, antibody response to SRBC, cytotoxic responses and production of interleukin-2. Clinical data based on the use of THF of natural sources in about 200 patients indicate that it regulates differentiation of T-cell precursors, leading to normalization of the ratio between helper and suppressor/cytotoxic subsets. THF reconstitutes the defective cell-mediated immunity in patients affected by various types of neoplasms and suffering from secondary immune deficiencies, as a result of chemo and/or radiotherapy. THF-gamma 2 was purified and synthesized and found to be an octapeptide which retains all the biological activity of the thymus extracts. It is presently available for extensive clinical use. PMID- 2196459 TI - Adenovirus vaccine strains genetically engineered to express HIV-1 or HBV antigens for use as live recombinant vaccines. AB - Types 4 and 7 adenovirus are currently used as live, oral vaccines for the prevention of adenovirus respiratory disease in military recruits. These vaccine strains have been genetically engineered in order to express HIV-1 or HBV antigens in infected cells. A dog model was developed to evaluate the immunogenicity of these recombinant vaccines. Dogs inoculated with live adenovirus-HBV recombinant vaccine produced antibody against hepatitis B surface antigen. PMID- 2196460 TI - Monoclonal antibodies against carcinoembryonic antigen (CEA) discriminate between CEA produced by gastrointestinal tumors and CEA produced by other tumors. AB - Carcinoembryonic antigen (CEA) is a common tumor marker. It is not specific since many tumor types express it. We report here the use of a series of monoclonal anti-CEA antibodies with apparent restricted activity. These antibodies reacted histochemically with CEA produced by tumors originating in the gastrointestinal tract, but they did not react with CEA-secreting tumors of nongastrointestinal origin. We have used this phenomenon to accurately diagnose the tumor of origin in 20 patients who had a CEA-producing metastatic tumor, but in whom the primary origin was clinically not yet discovered. The use of such antibodies for diagnostic purposes may be an adjunct to other methods in evaluating tumors of unknown origin. PMID- 2196461 TI - Mechanisms by which EGF receptor and TGF alpha contribute to malignant transformation. AB - Alterations affecting the epidermal growth factor/transforming growth factor alpha-responsive mitogenic pathway are frequently detected in malignancies. In particular, the epidermal growth factor receptor has been found overexpressed in a number of human tumors. Production and secretion of transforming growth factor type alpha has also been shown in several tumor cells but not in their normal counterparts. In this review we describe the establishment of in vitro model systems to study the transforming potential of these molecules and summarize our current understanding of the mechanisms involved in transformation by genes encoding a growth factor and a growth factor receptor. PMID- 2196462 TI - A clinical approach to Lyme disease. AB - Lyme disease (also known as Lyme borreliosis) is an emerging, newly described infectious disease with diverse clinical manifestations. The disease is caused by the spirochetal agent Borrelia burgdorferi, which is transmitted to humans by the bite of certain species of Ixodes ticks harboring the organism. The most readily identifiable clinical feature is the distinctive skin lesion, erythema migrans. If recently infected patients go untreated, approximately 15% will develop neurologic conditions (most commonly facial nerve palsy), 8% will develop myocarditis (typically with heart block), and 60% will develop migratory mono- or pauci-articular arthritis. Diagnosis depends on clinical suspicion, recognition of the characteristic signs and symptoms, and appropriate testing for antibody to B. burgdorferi. Serology for Lyme disease, although in need of better standardization, is most useful in diagnosing patients with manifestations of Lyme disease other than erythema migrans. All manifestations of Lyme disease are potentially treatable with either a beta-lactam antibiotic (for instance penicillin, amoxicillin, or ceftriaxone) or a tetracycline preparation. However, the optimal antimicrobial regimen, including choice of drug, drug dose, route of administration, and length of therapy, is unknown. Other important areas for future research include Ixodes biology and control, improved laboratory tests for diagnosis and for assessing response to therapy, and vaccine development. PMID- 2196463 TI - AIDS in Uganda--clinical and social features. PMID- 2196464 TI - Narcolepsy. PMID- 2196465 TI - A nosocomial outbreak of Salmonella enteritidis infection due to the consumption of raw eggs. PMID- 2196466 TI - Extracorporeal membrane oxygenation and the ethics of clinical research in pediatrics. PMID- 2196467 TI - [2 new treatment forms in lung tumors in the central airways; photodynamic therapy and brachytherapy]. PMID- 2196468 TI - [Orthostatic hypotension in the elderly]. PMID- 2196469 TI - [Bavaroise and an epidemic of Salmonella enteritidis]. AB - In the literature an association is made between the increasing prevalence of Salmonella enteritidis in poultry products and in the isolates of patients with gastroenteritis, without sufficient evidence of a causal relationship between the increasing prevalences. A microbiological and epidemiological analysis of a food poisoning incident among 239 visitors of a restaurant by way of food specific attack rates and food specific infection rates revealed an epidemic of 70 cases of S. enteritidis enteritis. The analysis supports the causal relationship with the consumption of an infected, unhygienically prepared egg product, in this case bavaroise. PMID- 2196470 TI - [Eurothemes. Are citizens of Europe-1992 being smoked out?]. PMID- 2196471 TI - Significance of lineage specific differentiation markers for complex classification of acute leukemias. I. Acute myeloid leukemias. AB - Acute leukemias are clonal malignant neoplastic diseases which do not originate from the transformation of totipotent hematopoietic stem cells but of progenitors committed to the myeloid, T-lymphatic or B-lymphatic differentiation lineage. The transforming event seems to be associated with a nonrandom aberrant DNA rearrangement. Although a leukemic population is clonal, originating from a single cell, it exhibits phenotypic, and sometimes even karyotypic, heterogeneity. Leukemic cells are allocated to a particular differentiation cell lineage on the basis of a positive finding of the lineage specific differentiation marker (LSDM) in the presented classification of acute leukemias. Criteria for common types of acute myeloid leukemias are described and the possible existence of several other types is discussed. PMID- 2196472 TI - Significance of lineage specific differentiation markers for complex classification of acute leukemias. II. Acute lymphoblastic leukemias. AB - Acute lymphoblastic leukemias originate from cells committed either to the T lineage (T-ALL) or B-lineage (nonT-ALL). Leukemic cells are allocated to these lineages according to the expression of lineage specific differentiation markers (LSDM), which are T-cell antigen receptors for the T-cell lineage and immunoglobulins for the B-cell lineage. T-ALL seem to be one type of disease, among nonT-ALL it is possible to distinguish several types of diseases according to the immunoglobulin expression and clinical findings. The specificity of monoclonal antibodies and other markers is discussed with regard to the classification of ALL and "hybrid acute leukemias" (hAL), the latter with cells differentiating into myeloid and lymphoid lineages. The existence of a single hAL has not yet been reliably proved with the use of LSDM. Short-term cultures of leukemic cells represent useful diagnostic tools particularly for acute unclassifiable leukemias. Present knowledge of karyotype findings in acute leukemias classified according to LSDM is reviewed and the necessity to introduce a complex classification on this basis stressed. PMID- 2196473 TI - Biochemical and immunological phenotype alterations in human monoblastoid cell line U-937 induced by physiological (interferon-alpha, retinoic acid) and nonphysiological (phorbol ester) inducers. AB - Human monoblastoid cell line U-937 was induced by recombinant or leukocyte human interferon-alpha, retinoic acid, by their combination, or by 12-0-tetradecanoyl phorbol-13-acetate (TPA), to express some differentiation-associated markers and characteristics. Induced biochemical alterations were studied with the aid of two dimensional electrophoretic analysis (isoelectrofocusing/SDS-PAGE) of 125I lactoperoxidase radioiodinated cell surface proteins, 35S-methionine metabolically radiolabeled cell proteins and 32P orthophosphate radiolabeled cell phosphoproteins. Alteration of immunophenotype markers was studied by continuous flow immunocytofluorometry with a panel of monoclonal antibodies directed to leukocyte antigens, cell proliferation, DNA, RNA, and protein synthesis by radioactive precursor incorporation techniques. Furthermore, cytochemical markers, cell adherence and nitroblue tetrazolium (NBT) reduction were utilized to follow the induction of differentiation-associated characteristics. Differential alterations of some immunophenotype markers induced by diverse inducers were observed. Major induced alterations included down-regulation of CD4 (induced by TPA, and to a lesser extent by IFN-alpha), TPA-induced decrease of cell surface expression of transferrin receptor (unmodified by IFN-alpha) and IFN alpha induced increase of antigen density (fluorescence intensity) of MHC class I antigen. Marked retinoic acid and interferon-alpha induced increase in membrane expression of antigen(s) detected by monoclonal antibodies BraC6 and BraC8, elicited with healthy donor's granulocytes, was also observed. PMID- 2196474 TI - Inositol lipid signaling during initiation of compensatory renal growth. PMID- 2196475 TI - Macroglossia and amyloidoma of the buttock: evidence of systemic involvement in dialysis amyloid. AB - A 48-year-old male on cuprophane haemodialysis for 18 years, with a history of dialysis arthropathy and recurrent carpal tunnel syndrome developed macroglossia and bilateral buttock tumoral masses. The tongue and buttock masses were biopsied. Histology of both biopsies showed amyloid deposits of the beta 2 microglobulin (B2M) variety. Amyloidomas in the gluteal region and macroglossia have not been previously described in amyloid derived from B2M. These findings suggest that systemic B2M amyloidosis can have a similar tissue distribution to AL amyloidosis. This case also stresses the importance of inspection of the tongue, and palpation of the gluteal region for masses, in the assessment of patients with dialysis arthropathy. PMID- 2196476 TI - Necrotizing myositis secondary to Serratia marcescens in a renal allograft recipient. AB - We describe a fatal case of spontaneous necrotizing myositis due to a highly resistant strain of Serratia marcescens in a renal transplant recipient. Though Staphylococcus aureus and Clostridium are the usual agents which cause either pyomyositis or necrotizing myositis, gram-negative bacteria are a dangerous and rarely suspected possibility. Such an aggressive disease should be promptly recognized because immunosuppression in susceptible hosts makes conservative management unsuccessful. The prognosis for myositis in immunodepressed hosts is poor and wide excision of all the necrotic muscles, leaving the wound open, and intensive antibiotic therapy are required. PMID- 2196477 TI - Short-term administration of colchicine to haemodialysis patients: plasma beta-2 microglobulin and phagocyte oxidative response. PMID- 2196478 TI - [What is the best treatment in massive pulmonary embolism: anticoagulants, thrombolytics or surgical embolectomy?]. AB - The aim of this work was to identify the best treatment available for massive pulmonary thromboembolism which still remains a frequent and sometimes lethal complication for surgical and non-surgical patients. The Authors underline the difficulties of diagnosis and the need for therapy at the earliest possible stage. At present, clinical management involves the use of: anticoagulants, thrombolytic agents and surgical embolectomy. In conclusion, the authors state that pulmonary thromboembolism, even when massive, has been transformed into a medically interesting pathology which can be cured using heparin and thrombolytic agents. However, surgical treatment is mandatory when patients reveal adverse effects to drug therapy, when medical therapy is insuccessful, or when patients are seriously ill with recurrent cardiac arrest. PMID- 2196479 TI - [Single cell preparation of the human heart. Technic of dissociation and isolation of myocytes]. AB - This paper describes a procedure of cellular dissociation which allows the isolation of single cells from the human heart while preserving their integrity and physiological function necessary for electrophysiological studies in vitro. During open heart surgery, biopsies were obtained from the right atrium of the beating heart in 16 patients immediately before starting the extracorporeal circulation. The tissue was immediately placed in a cardioplegic solution at 4 degrees, and subsequently in a free-calcium solution at 20 degrees from 20' to 30'. It was then exposed to the proteolytic action of Collagenase type I and Protease type VII (Sigma Chemical Co., St Louis, USA) at 35 degrees for a maximum of 5 hours. The cells were finally transferred into a Tyrode solution at room temperature. With this method we obtained up to 70% of intact human myocytes, 40% of which calcium-tolerant. The subsequent electrophysiological studies performed showed that the cells maintained their morphological and physiological properties. PMID- 2196480 TI - [Antibiotic prophylaxis with sulbactam/ampicillin in colon surgery]. AB - We evaluated the effectiveness of sulbactam/ampicillin (S/A) as a perioperative prophylaxis regimen in elective colic surgery (procedures lasting less than 4 hours). We studied 18 patients (11 males, 7 females; mean age 46 yrs, range 21 72), by an open, non-comparative trial: S/A was given soon before anesthesia (1 g + 2 g) and the same dose was repeated every 6 hours, up to 5 doses. The drug was well tolerated, and there were no side effects requiring the interruption of the prophylaxis. Infection rate was low (only one case of evident suppuration of the wound). PMID- 2196481 TI - [A rare thyroid vascular anomaly: a unique thyroid artery arising from the right carotid bifurcation]. AB - The evidence of thyroid vascular anomalies is is frequent and may manifest itself with an anatomic alteration. The absence of the inferior thyroid artery is reported in 1% of the cases, while a thyroid artery arising from the common carotid artery has been found in 2% of examined patients. In the observed case we retain that the rarity is not only due to the contemporary presence of two anomalies, but also to the presence of an anomalous vessel which arises from right carotideal bifurcation and bloody supplies either right lobular or left lobular of thyroid, thus resulting the sole gland's arterial vessel. PMID- 2196482 TI - Vitamin A and lung cancer. AB - In a dozen case-control and cohort studies, high intake of fruits and vegetables containing carotenoids has been associated with a reduced risk of lung cancer. In contrast, little relation has been found between intake of preformed vitamin A and this disease. Although initial studies suggested that persons with lower levels of serum retinol have higher future rates of lung cancer, this idea was not confirmed in subsequent investigations. Prediagnostic levels of beta-carotene in blood, however, have been inversely related with risk of lung cancer. Available data thus strongly support the hypothesis that dietary carotenoids reduce the risk of lung cancer, but the data are also compatible with the possibility that some other factor in these foods is responsible for the lower risk. Even if ultimately shown to be casual, the relation between diet and lung cancer is modest compared with the deleterious effect of cigarette smoking. PMID- 2196483 TI - American Journal of the Medical Sciences, Volume 245, 1963: Weanling diarrhea. PMID- 2196484 TI - Insulin regulation of lipoprotein lipase in adipocytes is not mediated by gene expression. PMID- 2196485 TI - Primary female syndromes: an update. PMID- 2196486 TI - Women in medicine since Flexner. PMID- 2196487 TI - Perspectives on women physicians in New York State: past, present, and future. PMID- 2196488 TI - History of the formation of the Committee on Women of the Westchester County Medical Society. PMID- 2196489 TI - The psychoneuroimmune network: expanding our understanding of immunity and disease. PMID- 2196490 TI - Epidemiology and health policy: how do we stop the band playing? PMID- 2196491 TI - Paediatric radiopharmaceutical dosimetry. PMID- 2196492 TI - The Intercollegiate Standing Committee on Nuclear Medicine. PMID- 2196493 TI - Augmentation of labor: does internal tocography result in better obstetric outcome than external tocography? AB - Labor was augmented in 250 patients for slow progress. These women were randomized to have uterine contractions recorded by either an external tocotransducer or an intrauterine catheter. Oxytocin was titrated to achieve an optimal frequency of contractions of six to seven every 15 minutes in each group; additional information on active contraction area profiles was available for those patients who had an intrauterine catheter. There was no statistically significant difference between the groups in the length of the post-augmentation period. The mean maximum dose of oxytocin was 11.1 mU/minute in the external tocography group and 11.0 mU/minute in the internal tocography group. Evidence of uterine hyperstimulation requiring temporary reduction of the oxytocin dose occurred in 19 and 20.2% of the patients in the external and internal tocography groups, respectively. Cesarean delivery was necessary in 12.6 and 16.9% of patients in the external and internal tocography groups, respectively, which is a nonsignificant difference. The incidence of low Apgar scores in the neonates and admission to neonatal intensive care was similar in both groups. The incidence of poor Apgar scores was not different between those who had transient hyperstimulation and those who had no hyperstimulation. In the management of augmented labor, monitoring of uterine contractions by intrauterine pressure catheters did not confer any advantage over tocography by external transducers. PMID- 2196494 TI - Measurement of cervical length in pregnancy: comparison between vaginal ultrasonography and digital examination. AB - Evaluation of the gravid cervix uteri is an important part of prenatal care, especially in the patient at risk for preterm birth. Seeking a method of cervical length measurement that could be used easily regardless of patient habitus, location of the cervix, and gestational age, we used a vaginal probe with a 240 degrees scanning angle in gravidas at various gestational ages to test the theoretical advantages of the wide scanning angle. Among the first 201 examinations, cervical length was measured successfully in 99.5% of cases. This success rate compares favorably with those of abdominal sonography and vaginal sonography using the standard 90 degrees scanning angle sector probes. We also compared this method with digital examination in a double-blind fashion. Only a fair degree of association between sonographic cervical measurements and measurements obtained by digital examination was found, reflected in a correlation coefficient of 0.49. PMID- 2196495 TI - Uterine and fetal Doppler flow changes from a single dose of a long-acting intranasal decongestant. AB - Oxymetazoline, an alpha-adrenergic agent, is the active vasoconstrictor in long acting intranasal decongestants. This investigation studied the effects of oxymetazoline on the maternal and fetal circulations. Twelve healthy gravid patients in the third trimester (27-39 weeks) underwent flow velocity measurements by the same sonographer using a pulsed Doppler system (ATL Ultramark 4 machine). Maternal and fetal indices were recorded 15 minutes before dosing, immediately thereafter, and at 15-minute intervals during the first 2 hours after the drug was given. No significant changes were found in either the maternal blood pressures or pulse rates. Blood flow velocities did not change significantly from baseline for the uterine arcuate artery, fetal aorta, or umbilical artery circulations. In no case did absolute blood flow velocity decrease significantly or systolic/diastolic ratios elevate to worrisome values. For uncomplicated pregnancies, we conclude there are no significant acute changes in the maternal and fetal circulations after a single dose of intranasal oxymetazoline. PMID- 2196496 TI - A randomized trial of routine prenatal ultrasound. AB - Nine hundred fifteen of 2171 pregnant patients had no indication for ultrasound at their first prenatal visit and were randomly assigned to receive either a single routine screening ultrasound or usual prenatal care. The estimated date of confinement was altered in 24.9% of routine-ultrasound patients and in 11.6% of usual-care patients through ultrasound examinations obtained for a subsequent clinical indication. Of these, 8.3% of routine-ultrasound and 5.2% of usual-care patients had gestational age errors of 2 weeks or more. There were no differences between the groups in inductions for post-dates pregnancy (7.0 versus 7.5%; P = .87), total inductions (22.6 versus 24.9%; P = .61), or adverse perinatal outcomes (6.7 versus 8.3%; P = .63). Both sets of twins were detected in the screened group. In the usual-care group, five of seven pairs of twins (71%) were diagnosed by 24 weeks' gestation. There was no benefit found from routine ultrasound as performed in this study. PMID- 2196497 TI - Prenatal diagnosis of congenital fetal arrhythmias by simultaneous pulsed Doppler velocimetry of the fetal abdominal aorta and inferior vena cava. AB - Various methods have been used for the diagnosis of congenital fetal arrhythmias. Currently, M-mode echocardiography is the most widely used method. However, good tracings are often difficult to obtain because of unfavorable fetal positions, resulting in long durations of examination. In early gestation, the fetal heart is often too small for clear M-mode echocardiography. Doppler velocity waveforms of the fetal inferior vena cava represent the right atrial activity, whereas those of the aorta reflect ventricular contraction. Because of the proximity of the vessels, it is easy to obtain simultaneous recording in opposite channels of Doppler waveforms from both vessels. A visual relationship between the atrial and ventricular contractions may be clearly established and a diagnosis may be made. The findings of simultaneous pulsed Doppler velocimetry of the fetal aorta and inferior vena cava were assessed in different types of congenital fetal arrhythmia: congenital heart block, premature atrial ectopic contractions, premature ventricular ectopic contractions, and supraventricular tachycardia. The correct diagnosis was made as early as 13 weeks' gestation, showing the application of this method in early pregnancy. PMID- 2196498 TI - Size of the fetal adrenal in bilateral renal agenesis. AB - Bilateral renal agenesis is a fetal malformation incompatible with extrauterine life. Accurate prenatal diagnosis is essential for patient counseling. False negative diagnoses have been reported and were attributed to the sonographic misidentification of apparently hypertrophied fetal adrenal glands as fetal kidneys. To study the relationship between renal agenesis and adrenal size, we reviewed autopsy records from 11 affected fetuses that had undergone careful autopsy and organ weight determination in our laboratory. Anomalies of distant structures were present in five affected fetuses. A sonographic diagnosis of adrenal hypertrophy had been made in two cases. In four of 11 fetuses, the glands had taken on a flattened discoid appearance. The autopsy records of 240 normal fetuses were similarly reviewed, and regression lines were generated for adrenal weight based on foot length and crown-rump length. The adrenal weights from affected fetuses were well within normal limits when compared with these normal regression lines and with organ weight standards from the literature. We conclude that adrenal hypertrophy is not a common finding in this syndrome and that the reported false-negative diagnoses are more likely attributable to a change in adrenal shape rather than a true increase in adrenal mass. PMID- 2196499 TI - Amniotic pressure in disorders of amniotic fluid volume. AB - Amniotic pressure was measured in 49 pregnancies with abnormal quantities of amniotic fluid. Among 17 with polyhydramnios, the pressure was always above the normal mean for gestation and exceeded the upper limit of normal in nine. In polyhydramnios, amniotic pressure correlated positively with the depth of the deepest pool (r = 0.65, P = .04) and negatively with fetal PO2 (r = -0.57, P = .03) and pH (r = -0.56, P = .04). Amniotic pressure was raised in all those with a deepest pool of greater than 15 cm, and was normal in all with a deepest pool less than 15 cm. Amniotic pressure fell significantly with drainage of amniotic fluid in those with raised pressure (mean 12.7 mmHg, 95% confidence interval 7.0 18.3; P = .002) but not in those with normal pressure (mean 0.3, 95% confidence interval -3.2 to +3.9; P = .82). Restoration of normal amniotic pressure in one pregnancy was accompanied by marked improvement in fetal acid-base status. Among 24 pregnancies with severe oligohydramnios, amniotic pressure was always below the normal mean, falling below the lower limit of normal in eight; whereas in another eight pregnancies with mild/moderate oligohydramnios, amniotic pressure was scattered evenly within the normal range. Amnioinfusion of 55-500 mL of normal saline in cases of severe oligohydramnios led to a significant rise in pressure (4.7 mmHg, 95% confidence interval 3.5-5.9; P less than .0001). We conclude that amniotic pressure is high in polyhydramnios and low in oligohydramnios. Pressure monitoring may be beneficial during amnioinfusion and therapeutic amniocentesis. PMID- 2196500 TI - Pelvic lymphocele following radical para-aortic and pelvic lymphadenectomy for cervical carcinoma: incidence rate and percutaneous management. AB - Thirty-six women, treated with radical hysterectomy (Piver types III-IV) plus systematic para-aortic and pelvic lymphadenectomy for cervical carcinoma, underwent serial postoperative ultrasound examinations to determine the incidence of lymphocele and the therapeutic efficacy of percutaneous catheter drainage. Pelvic lymphoceles, ranging in volume from 46-300 mL, occurred in eight patients (22.2%) between the 12-24th postoperative day. Percutaneous catheter drainage, inserted under local anesthesia, was used for a mean time of 14.5 days (range 4 32), resulting in a mean daily drainage of 92.2 mL and a mean total volume of 1727.5 mL per patient. Catheter drainage allowed complete clinical and sonographic remission in all cases, and only one asymptomatic recurrence was observed at 3-month and 6-month follow-up. Ultrasound-guided percutaneous catheter drainage has proved to be a well-tolerated, safe, and effective technique in the management of lymphocele that obviates the need for more invasive surgical procedures. PMID- 2196501 TI - A randomized clinical trial comparing Pipelle and Tis-u-trap for endometrial biopsy. PMID- 2196502 TI - Dental radiographic signs characteristic to Hallermann-Streiff syndrome. AB - A review of the literature and examination of a personally observed case led to the conclusion that anterior displacement of the temporomandibular joints provides a useful diagnostic criterion for the Hallermann-Streiff syndrome. PMID- 2196503 TI - Clinical application of dental implant with root of coated bioglass: short-term results. AB - During the last 4 years 73 dental implants with root-coated bioglass to replace one to three teeth in the premolar and molar sites of the mandible were inserted. The bonding ratio between implant and bone was observed clinically 1 year after implantation and installation of the superior structure. This ratio measured 52.4% to 63.3%. An acoustoelectric tester was developed that advanced our skills. The emphasis was placed on a tight fit between implant and surrounding bone. PMID- 2196504 TI - Displacement of a root form implant into the mandibular canal. AB - An unusual complication associated with the placement of osseointegrated root form implants is presented. Discussion of this complication focuses on treatment planning and anatomic considerations in the posterior mandible that impact the viability of implant placement. Vital structures in this location, including the mandibular canal, are often obscured on routine panoramic radiography. Tomograms of the maxilla or mandible can provide data on cortical plate thickness, location of vital structures, and the presence of large medullary spaces, information that will decrease the incidence of implant complications. PMID- 2196505 TI - The surgical mask unmasked: a review. PMID- 2196506 TI - Oral mucosal status and major salivary gland function. AB - Normal salivary function is considered to be critical for the maintenance of healthy oral mucosa. However, few studies have examined mucosal changes in patients with objectively documented salivary gland performance. In the present report, the mucosal status of 298 subjects being evaluated in a dry mouth clinic was assessed. A complete oral examination was performed and unstimulated and stimulated salivary samples were collected separately from the parotid and submandibular/sublingual glands. Data were analyzed according to diagnosis and salivary output after the assignment of an oral mucosal rating to each subject. In general, the mucosal surfaces were well preserved and infections were not seen. Patients evaluated for Sjogren's syndrome and radiation-induced xerostomia had the lowest salivary gland performance but displayed a mucosal status similar to denture-wearing healthy subjects or patients with normal salivary flow who had idiopathic xerostomia. However, those patients with a total lack of salivary flow rarely had normal-appearing oral mucosa. These results confirm a role for saliva in oral mucosal preservation and also suggest that other factors may act to maintain oral mucosal integrity. PMID- 2196507 TI - A pigmented adenomatoid odontogenic tumor. AB - Occasional reports have described the presence of melanin in various odontogenic lesions. A case of melanin pigmentation in an adenomatoid odontogenic tumor is described. PMID- 2196508 TI - Anomalous morphologic formation of deciduous and permanent teeth in a 5-year-old 15th century child: a variant of the Ekman-Westborg-Julin syndrome. AB - A gross morphologic anomaly affecting both the primary and secondary teeth of unknown cause is presented. A 5-year-old American Indian child exhibited macrodontia, extreme shovel-shaping, agenesis, three-rooted deciduous molars, dens invaginatus, and other less striking dental features. This case represents the earliest example of a variant of the Ekman-Westborg-Julin syndrome reported in the New World. PMID- 2196509 TI - Review of ophthalmic factors in dyslexia. AB - Dyslexia and the effect of visual problems on reading ability have long been subjects of controversy. This paper critically reviews the literature on the relationship between reading disability and visual acuity, refractive error, binocular vision anomalies, eye movements, ocular pathology and the transient and sustained visual systems. The limitations of much of the work in this field are described, with particular reference to the problems of subject selection and group matching. Tentative conclusions, with deference to the complex nature of dyslexia, are drawn and suggestions are made for future research. PMID- 2196510 TI - Age-related maculopathy. I: A review of its morphology and effects on visual function. AB - Age-related maculopathy (ARM) is a leading cause of permanent vision loss in elderly people. ARM therefore constitutes an important public health problem which will increase in magnitude as the number of aged people in the general population becomes greater. The consequences of this condition are exacerbated by the fact that treatment, especially of the atrophic form of the disease, is ineffective. While laser photocoagulation may be helpful in the exudative form of ARM, there is often an inexorable progression towards severe vision loss in these patients. Therefore considerable attention needs to be paid to the aetiology of ARM, the potential for its prevention or delayed onset and its recognition through functional disturbances. This is the first of three papers dealing with ARM and its effects on visual function. We review its morphology and the visual disturbances that may ensue. The second and third papers will discuss the nature and detection of the central visual field loss due to ARM. PMID- 2196511 TI - Liquid crystal lens review. AB - Liquid crystal lenses are possibly the spectacle lenses of the future for presbyopic corrections. They present a variable refractive index which can be used to produce the necessary addition needed for presbyopia. The variability of the refractive index is due to the fact that these materials are optically anisotropic. This effect is obtained by the application of an electric or magnetic field through the liquid crystal layer. A review of the literature relating to the evolution, the preparation and the operation of these lenses is given. A discussion is also included of the practical problems and drawbacks, which at present limit their use, and possible solutions. PMID- 2196512 TI - Reintroduction of continuous negative pressure ventilation in neonates: two-year experience. AB - Continuous negative pressure ventilation utilizes subatmospheric pressure around the thorax to improve oxygenation. It has not been routinely used since the mid 1970s. We treated 37 infants with the combination of continuous negative pressure (CNP) and intermittent mandatory ventilation (IMV), after failing to attain a PaO2 of greater than or equal to 50 torr on IMV alone. Lung diseases included pulmonary interstitial emphysema (PIE), respiratory distress syndrome (RDS), and pulmonary artery hypertension (PAH) due either to meconium aspiration syndrome (MAS) or other causes (non-MAS). All infants had evidence of severe parenchymal pulmonary disease, or pulmonary artery hypertension resulting in persistent hypoxemia and hypotension. In the PIE group, CNP was started later in the course of the disease, and both positive pressure and oxygen were maintained for a longer period. The group of infants with non-MAS PAH required CNP and positive pressure ventilation for the shortest period of time. The infants with PIE also had a greater incidence of bronchopulmonary dysplasia (BPD) and intraventricular hemorrhage (IVH). In addition, three patients with PIE died. In the non-MAS patients with PAH, no complications and no deaths occurred. The response to CNP was a rapid improvement in oxygenation in all groups with the greatest increase of PaO2 in the non-MAS PAH infants: from 30 torr prior to the initiation of CNP to 140 torr within 30 minutes. No significant changes in pH or PaCO2 occurred in any group. Significant decreases in ventilator rate, mean airway pressure (Paw) and FIO2 in peak inspiratory pressure were possible by 12 hours of CNP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196513 TI - Single breath versus panting technique in salbutamol delivery through a 750 mL spacing device. AB - Spacing devices have been widely advocated for asthmatic patients having difficulty actuating metered aerosols and co-ordinating inspiration. Studies have generally supported the slow inspiration/breath hold technique. This requires conscious respiratory control. Such control is often not possible in young children; consequently panting techniques are widely recommended. The panting technique has not been studied. The aim of this study was to compare the bronchodilator effectiveness of panting and the single breath maneuver, each followed by a breath hold, and each at functional residual capacity (FRC), using a Volumatic Space. The study design was a randomly allocated cross-over assessment of bronchodilator response for each technique. The drug dosage was controlled by limiting the inspired volumes of gas (single and cumulative) to the pretested inspiratory capacity. Two hundred micrograms of salbutamol was delivered into the spacer. Twenty-one patients were entered in the study and 15 (mean age +/- SD = 10.9 +/- 3.3 years) completed the protocol. There was no significant difference in bronchodilator response between the two groups. We conclude that the panting and the single breath techniques are equally effective in children of this age group. PMID- 2196514 TI - Correspondence between forced oscillation and body plethysmography during bronchoprovocation with carbachol in children. AB - We compared dose-response curves obtained with the forced oscillation technique (FOT) and with body plethysmography during bronchoprovocation in children. In 40 stable asthmatic children (age, 5-16 yr) we performed challenges with doubling concentrations of inhaled carbachol (0.15-10 mg/mL) until specific airway resistance SRaw had increased by 100% (PC100SRaw). The FOT-response was assessed by total respiratory system resistance (Rrs, cmH2O.1(-1).s) and reactance (Xrs, cmH2O.1(-1).s) from 8 to 26 Hz, expressed as mean Rrs (Rrs), mean Xrs (Xrs), Rrs at 8 Hz (Rrs8), and mean slope of Rrs (dRrs/df). Dose-response curves were analyzed for threshold concentrations (TC) causing a 3 SD change from baseline and sensitivity indices (SI) defined as differences between baseline and postchallenge values (at PC100SRaw) divided by baseline SD. Median TC of Rrs8, Rrs, Xrs, dRrs/df, and SRaw was 0.21, 0.30, 0.34, 0.41, and 0.42 mg/mL, respectively, indicating a slightly higher sensitivity for FOT. Median SI values of SRaw and Xrs (12.0 and 8.2; difference n.s.) were significantly higher than those of the other parameters. Multiple regression analysis revealed only the absolute change of Xrs (delta Xrs), baseline Rrs and age as significantly (P less than 0.001) correlated with the percentage change of SRaw (delta %SRaw). Best correlation (r = 0.86) with delta %SRaw was found for the function: FOT score = 102.5 X delta Xrs X exp(-0.196 X Rrs + 0.038 X age). Provocative concentrations estimated by this FOT score differed from PC100SRaw by less than one (two) concentration steps in 34 (40) out of 40 children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196515 TI - The spectrum of fusobacterial infections in children. PMID- 2196516 TI - Reliability of intradermal vaccination against hepatitis B for accelerated prophylaxis. PMID- 2196518 TI - Congenital malaria: a case report of a preventable disease. PMID- 2196517 TI - Disseminated neonatal trichosporosis associated with the hemophagocytic syndrome. PMID- 2196519 TI - Neonatal group A streptococcal septicemia. PMID- 2196520 TI - Side effects of methylphenidate in children with attention deficit hyperactivity disorder: a systemic, placebo-controlled evaluation. AB - The frequency and severity of 17 side effects presumably associated with stimulant medication were assessed during a rigorous, triple-blind, placebo controlled, crossover evaluation of methylphenidate, 0.3 and 0.5 mg/kg twice a day, in 83 children with attention deficit hyperactivity disorder. Side effects were rated by parents and teachers at the end of each weekly drug condition. Three children (3.6%) had side effects that were sufficiently serious to warrant immediate discontinuation of medication. Parent ratings indicated that only the side effects of decreased appetite, insomnia, stomachaches, and headaches increased significantly in frequency and severity during the two active medication doses as compared with the placebo condition. Fewer than half of the children experienced these side effects and among those who did, ratings of mean severity remained in the mild range. Teacher ratings showed little change over drug conditions, except on ratings of staring, sadness, and anxiety, which declined with increasing dose of medication. Parent ratings indicated that only the side effects of decreased appetite, insomnia, stomachaches, and headaches increased significantly in frequency and severity during the two active medication doses as compared with the placebo condition. Fewer than half of the children experienced these side effects and among those who did, ratings of mean severity remained in the mild range. Teacher ratings showed little change over drug conditions, except on ratings of staring, sadness, and anxiety, which declined with increasing dose of medication. Surprisingly, a high frequency of these behavior side effects were reported during the placebo condition. Stimulant medication within this therapeutic range, therefore, results in few, generally mild side effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196521 TI - Should promethazine in liquid form be available without prescription? AB - Promethazine, available by prescription only since its introduction in 1946, has been widely used for pediatric patients because of its antihistaminic, antiemetic, and sedative properties. Recently, it's makers have sought Federal Drug Administration approval to introduce two liquid over the counter allergy/cold/cough products containing promethazine as an active ingredient. Although millions of doses have been administered, promethazine use has not been free of risk. Promethazine has been reported to cause significant sedation, agitation, hallucinations, seizures, dystonic reactions, and possibly apparent life-threatening events or sudden infant death syndrome. The impact of these relatively uncommon adverse reactions on children would be minimal if parents would use over the counter promethazine only for appropriate indications and only in children greater than 2 years of age. However, according to results of research evaluating the use of various over the counter medications by families for their children, promethazine will be used inappropriately. Both its over the counter status, implying a certain margin of safety, and its formulation as a syrup, providing ease of administration, should increase its use in all age groups including that by children less than 2 years of age who may be most vulnerable to the adverse reactions associated with the drug's use. PMID- 2196522 TI - Relative efficacy of long-acting stimulants on children with attention deficit hyperactivity disorder: a comparison of standard methylphenidate, sustained release methylphenidate, sustained-release dextroamphetamine, and pemoline. AB - Twenty-two children with attention deficit-hyperactivity disorder underwent a double-blind, placebo-controlled, crossover evaluation of the efficacy of standard methylphenidate twice a day and comparable doses every morning of a sustained-release preparation of methylphenidate (SR-20 Ritalin), a sustained release form of dextroamphetamine (Dexedrine Spansule), and pemoline. The children were participating in a summer treatment program in which they engaged in recreational and classroom activities. Dependent measures include evaluations of social behavior during group recreational activities, classroom performance, and performance on a continuous performance task. Results revealed generally equivalent and beneficial effects of all four medications. Dexedrine Spansule and pemoline tended to produce the most consistent effects and were recommended for 10 of the 15 children who were responders to medication. The continuous performance task results showed that all four medications had an effect within 2 hours of ingestion, and the effects lasted for 9 hours. The implications of these results for the use of long-acting stimulant medication in children with attention deficit-hyperactivity disorder are discussed. PMID- 2196524 TI - Escherichia coli sepsis and prolonged hypophosphatemia following exertional heat stroke. PMID- 2196523 TI - Sucrose and delinquency: oral sucrose tolerance test and nutritional assessment. AB - Claims that juvenile delinquency may be associated with reactive hypoglycemia or nutritional deficiencies have received widespread attention but little objective evaluation. To assess the validity of these claims, nutritional and psychological indices of juvenile delinquents have been measured. Serum glucose and insulin profiles during an oral sucrose tolerance test were measured in 137 delinquent and 41 nondelinquent male adolescents aged 14 to 19. In addition, nutritional status of both populations was assessed by anthropometry (height, weight, arm circumference, triceps skin fold) and biochemical measures (hematocrit, red-blood cell thiamin, and serum copper, ferritin, and zinc). Delinquent subjects had slightly but significantly lower serum glucose values at four of six time points (fasting, 60 minutes, 120 minutes, 180 minutes) and higher serum insulin values at one time point (30 minutes) compared with nondelinquent subjects. Changes in glucose from fasting levels indicate that these subjects were regulating serum glucose adequately, but doing so at lower values; changes in insulin from fasting levels indicate that black delinquents initially secreted more insulin than either white subject group. There were no significant associations between excursions in serum glucose or insulin and any adrenergic signs or symptoms of low blood glucose levels. Nutritional status of incarcerated delinquents did not differ from that of nonincarcerated subjects on most measures. Although the significantly lower serum glucose levels and higher serum insulin levels are intriguing, no support is offered by results of this study for allegations that sucrose ingestion causes reactive hypoglycemia in juvenile delinquents or that delinquent male adolescents are at greater risk nutritionally than male adolescents of the same age who are not delinquent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196525 TI - Coagulase-negative staphylococcal bacteremia in neonates: confusion continued. PMID- 2196526 TI - The total costs of ultrasonography. PMID- 2196527 TI - [Combined treatment of homeostasis disorders caused by leukemic tumor and its treatment in children]. PMID- 2196528 TI - [Ways of reducing perinatal mortality in critical conditions of the fetus]. PMID- 2196529 TI - [Kidney diseases and major histocompatibility complex]. PMID- 2196530 TI - Aminoglycoside therapy. Current use and future prospects. AB - The microbiological, pharmacokinetic, toxicological and clinical aspects of aminoglycosides are reviewed. Aminoglycosides still have an important place in serious infections in neutropenic patients, endocarditis and Pseudomonas aeruginosa infections, all in combination with beta-lactams. Monotherapy (with streptomycin) is indicated in less common diseases like tularemia and bubonic plague. Several experimental studies support a once-daily dosing regimen for aminoglycosides (comparable or better efficacy with less ototoxicity and nephrotoxicity). Only a very limited number of prospective comparative studies have been performed, and much more data on efficacy, development of resistance and toxicity is needed before once-daily administration can be recommended. The choice of an aminoglycoside should be based primarily on the local sensitivity patterns and cost. Differences in ototoxicity and nephrotoxicity are usually minor. If the acquisition costs of amikacin decline, it is to be expected that amikacin will be the aminoglycoside of choice. PMID- 2196531 TI - Drug-utilization studies in The Netherlands. AB - Drug-utilization research is a research area of increasing importance, both in the Netherlands and elsewhere. In this article an overview of the situation in the Netherlands is given. Three types of studies are distinguished: descriptive studies, studies of the determinants of drug use and studies of the impact of drug use. Descriptive studies are needed to understand the present situation and to detect problems. If these problems are to be solved it is important to understand the factors that determine drug use. In the Netherlands research in the latter area is focused on the influence of policy measures and of educational measures for physicians, as well as for the general public. The main body of research into the impact of drug use is the study of adverse effects, but increasingly attention is paid to the effect on quality of life in a broader sense. A number of data bases exist that enable drug-utilization research. At present one of the main problems concerning the data bases is the absence of adequate diagnosis-related drug-utilization data. Despite the existence of a number of shortcomings and problems, the general impression of drug-utilization research in the Netherlands is one of a flourishing field of study. PMID- 2196532 TI - Utilization patterns of non-steroidal anti-inflammatory drugs in an open Dutch population. AB - Non-steroidal anti-inflammatory drugs represent an important drug class in ambulatory care. A utilization study among half a million persons showed that 8.6% could be identified as having used one or more non-steroidal anti inflammatory drugs (excluding salicylates) in 1987. Data were drawn from a representative sample of pharmacy records which comprise full medication histories of individual patients. Overall utilization of non-steroidal anti inflammatory drugs was 10.8 defined daily doses/(1000 persons.day). Approximately three quarters of the patients are 'incidental' users and receive non-steroidal anti-inflammatory drugs for a relatively short time (30 days or less). Patients who were identified as 'regular' (31-210 days of therapy) and 'heavy' (greater than 210 days of therapy) users, accounted for 21.2% respectively 4.8% of all users. 'Heavy' users are responsible for 17.3% of all non-steroidal anti inflammatory drug prescriptions. Especially the elderly and females are prone to be 'heavy' users. Five drugs account for 90.4% of all prescriptions (diclofenac, ibuprofen, naproxen, piroxicam, indomethacin). A total of 71.1% of the patients with more than one prescription for non-steroidal anti-inflammatory drugs switched in therapy. There are two classes of concomitant drug use especially relevant with respect to detecting non-steroidal anti-inflammatory drugs associated risks: H2 blockers and antacids (belonging to anatomical therapeutic and chemical anatomic class A) and diuretics (belonging to anatomical therapeutical chemical anatomic class C). More than half of the 'heavy' users showed concomitant use of drugs in these classes. PMID- 2196533 TI - Reconceptualizing TMJ diagnosis. I. PMID- 2196534 TI - The pharmacology of adenosine. AB - Adenosine is a purine nucleoside present in every cell of the human body. It is released into the extracellular space under physiologic and pathophysiologic conditions characterized by increased oxygen demand:supply ratio. Adenosine can exert a wide spectrum of effects in various organs and tissues. Exogenous adenosine has a wide spectrum of effects in experimental animal models as well as humans. The pharmacokinetics, pharmacodynamics, and the interaction of adenosine with other drugs are reviewed. PMID- 2196535 TI - Pharmacotherapy of obsessive-compulsive disorder. AB - Obsessive-compulsive disorder (OCD) is a potentially devastating illness, both to the patient and family members. Its etiology is unclear, but some evidence points toward dysfunction in an orbitofrontal striatal-limbic neuronal loop. Although many agents have been used, clomipramine, a tricyclic antidepressant, appears to be the most promising therapy. Clomipramine was approved by the Food and Drug Administration and released for general use in early 1990 under the brand name Anafranil. Clomipramine's adverse effect profile is similar to that of currently marketed tricyclic antidepressants; however, it is associated with a higher frequency of seizures, estimated to be 0.7%. Although other serotonergic agents such as fluoxetine have shown promise in OCD, they have been studied only in a limited number of patients. Other agents, with the possible exception of monoamine oxidase inhibitors, either have resulted in inconsistent improvement or have been reported in an anecdotal fashion. PMID- 2196536 TI - A multiinstitutional evaluation of the analgesic efficacy and safety of ketorolac tromethamine, acetaminophen plus codeine, and placebo in cancer pain. AB - Seventy-five patients with moderate to severe cancer pain were randomly assigned in a double-blind fashion to receive first-dose ketorolac tromethamine 10 mg orally, acetaminophen 600 mg plus codeine 60 mg orally, or placebo, followed by subsequent doses of ketorolac or acetaminophen plus codeine four times daily for 7 days. Patient characteristics were similar among the treatment groups. The first-dose observation documented that both ketorolac and acetaminophen plus codeine produced an equivalent reduction in cancer pain and were superior to placebo as measured by pain intensity differences and pain relief. Multidose comparison documented a small but statistically significant advantage in mean daily pain relief favoring acetaminophen plus codeine, although there were no differences in mean daily ratings of overall effects for either study medication. Adverse symptoms were acceptable with both ketorolac and acetaminophen plus codeine. We conclude that ketorolac has significant analgesic activity in patients with cancer pain, although its precise role in the treatment regimen of these patients remains undefined. PMID- 2196537 TI - Aminoglycosides: another look at current and future roles in antimicrobial therapy. PMID- 2196538 TI - Dopamine versus dobutamine: are all the facts there? AB - During the last 5 years we believe that the prescribing of dobutamine has increased over that of the older agent dopamine. The literature reports advantages such as less tachycardia, less peripheral vasoconstriction, and fewer increases in intracardiac pressures with dobutamine as opposed to dopamine. After a thorough review of the literature, we were unable to find conclusive evidence of these initial findings, and present several studies to show potential flaws in their interpretation that may help explain the increased use of dobutamine over dopamine. The overuse of dobutamine, if it does exist, must be dealt with by pharmacy departments in an informed, yet unbiased fashion, to aid in preventing the continued escalation of health care costs. PMID- 2196539 TI - Evaluation of the EZ-SCREEN enzyme immunoassay test for detection of cocaine and marijuana metabolites in urine specimens. AB - The EZ-SCREEN Cannabinoid/Cocaine test is a qualitative enzyme immunoassay card test for the detection of cannabinoid and cocaine metabolites in urine specimens. Results are available in about three minutes. The test kit costs approximately $12.00 per two-drug test, and there are no additional expenses for analytical equipment. We compared the results of the EZ-SCREEN test with results of specimens analyzed by gas chromatography/mass spectrometry (GC/MS) for 36 clinical specimens positive for cannabinoids (marijuana), 38 clinical specimens positive for benzoylecgonine (cocaine), and 33 drug-free specimens. Results from our study for marijuana included: sensitivity = 92%; specificity = 89%; and efficiency = 95, 67, and 87%, respectively. In the present study, there were five false-positive tests for cocaine and one false-positive test for cannabinoids. As with all screening test results, confirmation of positive specimens by a more specific quantitative analytical method such as GC/MS is recommended. PMID- 2196540 TI - Vomiting. PMID- 2196541 TI - Latex agglutination for the rapid diagnosis of streptococcal pharyngitis: use by house staff in a pediatric emergency service. AB - A rapid latex agglutination (LA) method was evaluated in 2401 consecutive pediatric patients presenting to an emergency service with suspected group A beta hemolytic streptococcal pharyngitis. LA tests were performed by the treating physicians, who were not blinded to the clinical condition of the children and who made therapeutic decisions based on the results of the tests. When compared with anaerobic culture, the LA method had a sensitivity of 91%, a specificity of 82%, and a positive predictive value of 43%. There was a marked seasonal variation in the positive predictive value: 62% in winter and 16% in summer. However, even in peak streptococcal pharyngitis season (January to March), basing therapy on a positive LA test leads to the unnecessary treatment of a large number of patients. Therefore, we cannot recommend the routine performance of this test by all practitioners in all clinical settings. PMID- 2196542 TI - Is nifedipine phototoxic? AB - Circumstantial evidence of phototoxicity of nifedipine is poor, being based only on uncontrolled clinical evidence. The authors have assessed nifedipine phototoxicity in vitro by photohemolysis and Candida albicans tests and found it measurable at 10 and 100 micrograms/ml. These dosages exceed the 0.1 microgram/ml blood levels that are usually attained in vivo. PMID- 2196543 TI - Spectral reflectance of human skin in vivo. AB - A newly developed skin reflectance spectrophotometer was evaluated for measurements of both melanin pigmentation and erythema. Physiological changes in blood flow and blood content in normal humans were induced by compression with an arm cuff during recording of skin reflectance spectra. Reflectance spectra of UV induced erythema were also recorded and compared with laser-Doppler flow measurements. Spectral reflectance measurements were found to be highly sensitive in determining minimal erythema, which was not clinically detectable. The measurements of erythema using reflectance spectroscopy and UV irradiation were very highly correlated (r = 0.996). It was possible to calculate the in vivo absorbance of oxygenized haemoglobin. The melanin pigmentation following UV irradiation was quantified by reflectance spectroscopy and correlates highly with the dose of UV irradiation (r = 0.995). Furthermore, regional variations in skin melanin and haemoglobin were analysed for fair Caucasian skin. PMID- 2196544 TI - Hibernoma of the pericardium presenting as pericardial effusion in a child. PMID- 2196545 TI - Polyorchidism in a newborn: case report and review of the literature. AB - A case of polyorchidism in a newborn is reported. The left scrotum contained two testes sharing the same epididymis and vas deferens. The histometric testicular parameters were normal in the three testes, except for a slightly reduced tubular fertility index in the supernumerary testis. PMID- 2196546 TI - Juvenile granulosa cell tumor. AB - A 2-year-old girl presented with isosexual precocity, and a juvenile granulosa cell tumor of the left ovary was removed. The tumor was unusual in that striated muscle differentiation of the tumor cells was demonstrated. This suggests that the mesenchymal cells retain the potential for divergent differentiation. PMID- 2196547 TI - Left atrial atheromatosis in childhood nephrotic syndrome. AB - Three male children who had onset, at approximately age 2 years, of nephrotic syndrome, which progressed to renal insufficiency had left atrial atheromatosis at autopsy disproportionate to the degree of aortic or vascular atheromatosis found. The atrial atheromatous process was distributed in elongated nodules, which had a ridged or corduroy-like appearance on gross examination. Two of the patients showed renal lesions of advanced focal glomerulosclerosis, but one had membranoproliferative glomerulopathy, suggesting that the "syndrome" of early onset nephrotic syndrome progressing to renal insufficiency, hyperlipidemia, and exaggerated left atrial atheromatosis, of which association we have not found a specific report, is etiologically heterogeneous. The patients reported died in 1943, 1952, and 1963. Whether more recent methods of treatment of nephrotic syndrome, hyperlipidemia, or chronic renal insufficiency in children have altered the incidence of such disproportionate left atrial atheromatosis is not known. PMID- 2196548 TI - Multivisceral dysplastic lesions in a patient with tuberous sclerosis and Langerhans cell histiocytosis. AB - Collections of large cells and smaller satellite-like cells arranged in an autonomic ganglion-like pattern and resembling the white matter lesions of tuberous sclerosis were found in the thymus, lungs, liver, appendix, and heart of an 8-month-old infant who exhibited other pathologic findings of tuberous sclerosis (rhabdomyomas of the heart and multiple kidney cysts). Focal cytoplasmic staining for S-100 and GFAP was noted in some large cells, suggesting neural (probably schwannian) differentiation. Dysplastic neurogenic foci appearing in internal organs may represent another morphologic marker of tuberous sclerosis. The simultaneous presence of Langerhans cell histiocytosis produced an unusual combination not previously reported. PMID- 2196551 TI - Use of ultra-sound for bleeding in early pregnancy. PMID- 2196550 TI - Occupational cancer: interaction with life style factors. AB - It is argued that as the major occupational cancer risks become matters of historical interest, research epidemiologists working in the field should broaden their approaches to encompass life style factors. In the investigation of possible low-cancer risks, it no longer makes any sense to confine their data collecting activities solely to exposure to dusts and chemicals at work and to regard exposure to chemicals at home, in the garden or during leisure activities simply as possible confounding variables. Furthermore it is becoming more and more meaningless to undertake any epidemiological investigation aimed at detecting or defining a low level of cancer risk without taking into account what and how much, for example, people eat, drink and smoke. Possible exposure to chemicals at work is increasingly becoming a source for confounding variables in relation to life-style-associated cancer risks, as distinct from life-style being a source of confounding variables in epidemiological studies of occupation associated cancer risks. PMID- 2196552 TI - Cardiovascular dopamine receptors: role of renal dopamine and dopamine receptors in sodium excretion. AB - Research efforts in the area of peripheral dopamine have now established the presence of two distinct subtypes--DA1 and DA2--of DA receptors, and have identified a potential role for dopamine produced within the kidney in the control of renal sodium excretion. Selective DA1 and DA2 receptor agonists are being developed because they exhibit therapeutic potential for treatment of cardiovascular and renal disorders. Furthermore, basic research efforts are aimed towards identifying the stimulus and/or stimuli for the production of dopamine within the kidney and characterizing the cellular signalling processes involved in mediating the renal effects of dopamine and selective DA receptor agonists. PMID- 2196553 TI - Pethidine is unsuitable for buccal administration. PMID- 2196549 TI - General surgery. PMID- 2196554 TI - Rationale for selective COMT inhibitors as adjuncts in the drug treatment of Parkinson's disease. PMID- 2196555 TI - Codeine in analgesic doses does not depress respiration in patients with severe chronic obstructive lung disease. AB - Nineteen normocapnic patients with chronic obstructive lung disease participated in an open single dose safety study (part one) followed by a randomized double blind cross-over study comparing two seven-days treatment periods of 1 g of paracetamol t.i.d. with 60 mg of codeine plus 1 g of paracetamol t.i.d., respectively (part two). In part one, continuous monitoring after a single dose of 2 g of paracetamol and 120 mg of codeine revealed no deterioration in the respiration and gas tensions. In part two, respiratory parameters and arterial gas tensions were recorded one hour after the last morning dose. PaCO2 increased insignificantly (0.05 less than P less than 0.10) by a median of 0.38 kPa during treatment with codeine and paracetamol compared to treatment with paracetamol alone. PaO2 decreased by 0.12 kPa (P greater than 0.10). There was no correlation between changes in PaCO2 and changes in PaO2. FVC, FEV1 and dyspnoea at rest were unchanged. Gastrointestinal side effects were reported significantly (P less than 0.02) more often during treatment with codeine plus paracetamol. There was no correlation between the plasma concentration of codeine or morphine and changes in respiratory parameters or adverse effects. The limitation for the short time clinical use of codeine as an analgesic to normocapnic patients with severe chronic obstructive lung disease in stable phase seem to be gastrointestinal side effects. PMID- 2196557 TI - An attempt to unify the structure of polymerases. AB - With the great availability of sequences from RNA- and DNA-dependent RNA and DNA polymerases, it has become possible to delineate a few highly conserved regions for various polymerase types. In this work a DNA polymerase sequence from bacteriophage SPO2 was found to be homologous to the polymerase domain of the Klenow fragment of polymerase I from Escherichia coli, which is known to be closely related to those from Staphylococcus pneumoniae, Thermus aquaticus and bacteriophages T7 and T5. The alignment of the SPO2 polymerase with the other five sequences considerably narrowed the conserved motifs in these proteins. Three of the motifs matched reasonably all the conserved motifs of another DNA polymerase type, characterized by human polymerase alpha. It is also possible to find these three motifs in monomeric DNA-dependent RNA polymerases and two of them in DNA polymerase beta and DNA terminal transferases. These latter two motifs also matched two of the four motifs recently identified in 84 RNA dependent polymerases. From the known tertiary architecture of the Klenow fragment of E. coli pol I, a spatial arrangement can be implied for these motifs. In addition, numerous biochemical experiments suggesting a role for the motifs in a common function (dNTP binding) also support these inferences. This speculative hypothesis, attempting to unify polymerase structure at least locally, if not globally, under the pol I fold, should provide a useful model to direct mutagenesis experiments to probe template and substrate specificity in polymerases. PMID- 2196556 TI - Fibronectin and laminin in the early human placenta. AB - The distribution of fibronectin and laminin was investigated in early intrauterine and ectopic tubal pregnancy using a standard immunoperoxidase technique on paraffin-embedded tissues. Localization of both fibronectin and laminin appeared identical in intrauterine and in ectopic pregnancy. Fibronectin was demonstrated in chorionic villous stroma, in the distal cytotrophoblast cell columns, in infiltrating mononuclear extravillous trophoblast and in endovascular trophoblast. Villous trophoblast and multinucleate interstitial trophoblast did not label. Extracellular fibronectin was demonstrated amidst sheets of infiltrating extravillous trophoblast. Laminin distribution was similar to that described for fibronectin but laminin was also present in the basement membrane of villous cytotrophoblast. Both fibronectin and laminin showed a pericellular distribution around decidual stromal cells. This study demonstrates further heterogeneity of human trophoblast populations. The presence of fibronectin in infiltrating extravillous trophoblast, endovascular trophoblast and in the distal columns may enhance trophoblast adhesion to maternal tissues and facilitate trophoblast migration. PMID- 2196558 TI - Site-directed mutagenesis of aspartic acid 372 at the ATP binding site of yeast phosphoglycerate kinase: over-expression and characterization of the mutant enzyme. AB - A new phosphoglycerate kinase over-expression vector, pYE-PGK, has been constructed which greatly facilitates the insertion and removal of mutant enzyme genes by cleavage at newly introduced BamHI sites. This vector has been used to prepare mutant protein in appreciable (100 mg) quantities for use in kinetic, crystallographic and NMR experiments. Aspartate 372 is an invariant amino acid residue in genes known to code for a functionally active PGK. The function of this acidic residue appears to be to help desolvate the magnesium ion complexed with either ADP or ATP when this substrate binds to the enzyme. Both crystallographic and nuclear magnetic resonance experiments show that the replacement of the residue with asparagine has only minimal effects on the overall structure. The substitution of the charged carboxyl group with that of the neutral amide affects the binding of the nucleotide substrate as predicted but not, as might have been expected, the binding of 3-phosphoglycerate. The overall velocity of the enzymic reaction (Vmax) is reduced 10-fold by the substitution of aspartic acid 372 by an asparagine residue (D372N). This reduction in Vmax is considerably less than one would expect from its known position within the structure of the enzyme. This result therefore poses questions about our understanding of charged groups at the active centres of enzymes and of the reason for their apparent conservation. PMID- 2196559 TI - Protein engineering of alcohol dehydrogenases: effects of amino acid changes at positions 93 and 48 of yeast ADH1. AB - By protein engineering we have investigated changes to two amino acid residues (Trp93 and Ser48) in the substrate pocket of yeast alcohol dehydrogenase 1. Upon changing Thr48 to serine we produced an enzyme which has markedly greater activity towards aliphatic alcohols with chain length up to 8, together with a general increase in catalytic activity (V/K). Changes at position 93 were less pronounced, with the Phe enzyme being more active than the parent towards the range of alcohols but with the alanine enzyme showing very little difference from the wild-type. Enzymes with the double changes at 48 and 93 showed increased activity towards alcohols with 3-8 carbons but the increases were not additive over the single changes. The enzymes with changes at the two positions would metabolize both stereoisomers of 2-octanol whereas the parent ADH would attack only one of them. None of the engineered enzymes would attack cyclohexanol or aromatic alcohols. The results are in general agreement with the prediction that reducing the size of amino acids in the substrate pocket would enhance the ability to oxidize alcohols larger than ethanol. PMID- 2196560 TI - Effect of inhibitory activity of mutation at reaction site P4 of the Streptomyces subtilisin inhibitor, SSI. AB - The protein Streptomyces subtilisin inhibitor, SSI, efficiently inhibits a bacterial serine protease, subtilisin BPN'. We recently demonstrated that functional change in SSI was possible simply by replacing the amino acid residue at the reactive P1 site (methionine 73) of SSI. The present paper reports the additional effect of replacing methionine 70 at the P4 site of SSI (Lys73) on inhibitory activity toward two types of serine proteases, trypsin (or lysyl endopeptidase) and subtilisin BPN'. Conversion of methionine 70 at the P4 site of SSI(Lys73) to glycine or alanine resulted in increased inhibitory activity toward trypsin and lysyl endopeptidase, while replacement with phenylalanine weakened the inhibitory activity toward trypsin. This suggests that steric hindrance at the P4 site of SSI(Lys73) is an obstacle for its binding with trypsin. In contrast, the same P4 replacements had hardly any effect on inhibitory activity toward subtilisin BPN'. Thus the subsite structure of subtilisin BPN' is tolerant to these replacements. This contrast in the effect of P4 substitution might be due to the differences in the S4 subsite structures between the trypsin-like and the subtilisin-like proteases. These findings demonstrate the importance of considering structural complementarity, not only at the main reactive site but also at subsites of a protease, when designing stronger inhibitors. PMID- 2196562 TI - Rapid and efficient site-specific mutagenesis. PMID- 2196561 TI - A dual-affinity gene fusion system to express small recombinant proteins in a soluble form: expression and characterization of protein A deletion mutants. AB - A novel gene fusion system to express and purify small recombinant proteins in Escherichia coli has been constructed. The concept allows for affinity purification of soluble gene products by sequential albumin- and Zn2(+)-affinity chromatography. The dual-affinity system is well suited for expression of unstable proteins as only full-length protein is obtained after purification and proteins gain proteolytic stability in the fusion protein. Here we show that the dual-affinity approach can be used for the expression of various unstable derivatives of a single IgG-binding domain based on staphylococcal protein A. Analysis of the proteolytic stabilities and the IgG-binding properties of the different mutant proteins suggest that the model for the structure of an IgG binding domain must be re-evaluated. PMID- 2196563 TI - Left atrial myxoma in a Chinese octogenarian. PMID- 2196564 TI - Complete amino acid sequence of bovine glia maturation factor beta. AB - The protein glia maturation factor beta, isolated from bovine brain, has been sequenced by automated Edman degradation and tandem mass spectrometry of overlapped peptide fragments generated by cyanogen bromide cleavage and enzymatic digestion with trypsin, chymotrypsin, and endoproteinases Asp-N and Lys-C. The protein has 141 amino acid residues and possesses no potential N-glycosylation sites. It contains three cysteines (at positions 7, 86, and 95), three methionines (at positions 33, 101, and 102), and one tryptophan (at position 132). The blocked amino terminus as determined by tandem mass spectrometry is an N-acetylated serine. The carboxyl terminus is a histidine. To our knowledge, the sequence shows no significant homology with other sequenced proteins. The molecular weight calculated from the sequence information is 16,582. PMID- 2196565 TI - Yeast Gal11 protein mediates the transcriptional activation signal of two different transacting factors, Gal4 and general regulatory factor I/repressor/activator site binding protein 1/translation upstream factor. AB - GAL11 was first identified as a gene required for full expression of some of the galactose-inducible genes in the yeast Saccharomyces cerevisiae. A null mutation within the GAL11 locus causes defects in mating, growth on nonfermentable carbon sources, and sporulation of gal11 homozygotes. The mating defect was observed only in MAT alpha gal11 strains. Northern hybridization analysis revealed that a gal11 mutation impaired transcription of alpha-specific genes (MF alpha 1 and STE3) but not of an a-specific gene (STE2). Furthermore, this mutation reduced expression of the MAT alpha locus, suggesting that a deficiency in MAT alpha 1 protein is responsible for the reduced expression of alpha-specific genes. Since general regulatory factor I (GRFI)/repressor/activator site binding protein 1 (RAP1)/translation upstream factor (TUF) is believed to be an activator of MAT alpha expression, we examined whether PYK1, which is known to be regulated by GRFI/RAP1/TUF, is also affected by the gal11 mutation. It was determined that the level of PYK1 message was significantly lowered by the mutation. The requirement for functional GAL11 in transcriptional activation was bypassed when either the upstream activating sequence of galactose-inducible genes or of PYK1 was placed very close to the TATA box, suggesting that one of the Gal11 protein functions is to mediate the activation signal of Gal4 and GRFI/RAP1/TUF, when the respective binding site is situated at the naturally occurring distance from the TATA box. PMID- 2196566 TI - The B subunit of a rat heteromeric CCAAT-binding transcription factor shows a striking sequence identity with the yeast Hap2 transcription factor. AB - CBF is a heteromeric mammalian transcription factor that binds to CCAAT sequences in a number of promoters such as the two type I collagen promoters, the albumin promoter, the major histocompatibility complex class II promoter, and others. It is composed of two components, A and B, that are both needed for DNA binding. We have isolated a rat cDNA containing the complete 341-amino acid coding sequence of the B component of CBF. Expression of this cDNA in vitro generates a polypeptide that shows the same dependency on the A component as the native B component in the formation of a complex with a CCAAT-containing DNA. The C terminal portion of the B component from residue 260 to residue 312 shows a 75% sequence identity with a portion of the Hap2 protein, a component of a heteromeric CCAAT-binding protein in yeast. In contrast, the rest of the protein shows little sequence homology with Hap2, although both proteins contain glutamine-rich domains. In the B component of CBF this domain spans the amino terminal 60% of the protein, whereas in Hap2 this domain is much smaller. Hence, only a few changes in one domain of this protein were tolerated during evolution between yeast and mammals, whereas the rest of the protein diverged much more extensively. PMID- 2196567 TI - Developmental repression of growth and gene expression in Aspergillus. AB - Asexual reproductive development can be initiated in Aspergillus nidulans in the presence of excess nutrients through artificial induction of the developmental regulatory genes brlA or abaA by fusing the genes to the promoter from the alcohol dehydrogenase I gene (alcA) and culturing cells in the presence of an inducing alcohol. Artificially induced development completely inhibits growth and represses expression of the endogenous alcA gene and the coordinately controlled aldehyde dehydrogenase gene (aldA). Repression of alcA and aldA expression probably occurs at both the transcriptional and posttranslational levels. We propose that developmental induction results in a generalized metabolic shutdown, leading to an inability of cells to acquire nutrients from the growth medium. Self-imposed nutrient limitation could reinforce the primary developmental stimulus and ensure progression through the asexual reproductive pathway. PMID- 2196568 TI - Monoclonal antibody R2D5 reveals midsagittal radial glial system in postnatally developing and adult brainstem. AB - Radial glial cells and their processes play critical roles in organizing the spatial arrangement of the nervous system in the embryonic brain. It has been thought that following completion of their roles in the embryo, most of the radial glial processes disappear before or shortly after birth. Here we use R2D5, a monoclonal antibody to a soluble cytosolic protein, to demonstrate that a specific system of midsagittal radial glial cells persists in postnatal and adult brain. In the brainstem of postnatally developing and adult rabbits and cats, the R2D5-positive processes of radial glial cells were observed to be arranged in a precisely parallel array at the midsagittal seam. These radial glial processes formed a continuous palisade separating the right and left brainstem. In early postnatal animals, R2D5-positive radial processes were found to reach the pial surface and to cover the entire midsagittal seam of the brainstem. These processes embraced dendrites and somata of neurons in almost all of the midsagittal nuclei, including the raphe nuclei, suggesting that the radial glial cells may interact with the midsagittal groups of neurons. In addition, the palisade of R2D5-positive radial processes formed loose openings for crossing axonal bundles at the midline decussations of fiber tracts. In more mature brains, somata of R2D5-positive radial glial cells that had migrated ventrally were observed within the palisades, and in adult cats, most of the R2D5-positive radial processes were found to have retracted from the ventral parts of the midsagittal seam. The spatial arrangement of R2D5-positive processes suggests that they may have persistent functional roles as an interface between ventricular humoral signals and midsagittal groups of neurons in the postnatally developing brainstem and in the adult brainstem. The structure of the midline glial system suggests also that it plays a role in organizing the spatial arrangement of decussating axons during development. PMID- 2196569 TI - High-resolution two-dimensional polyacrylamide gel electrophoresis reveals a glucose-response protein of 65 kDa in pancreatic islet cells. AB - High-resolution two-dimensional PAGE was used to search for glucose-response proteins in isolated pancreatic islets that were labeled with [35S]methionine at ambient glucose concentrations of 0-18 mM. A 65-kDa protein, isoelectric focusing point of approximately 6.6-7.0, was discovered that showed at least a 20-fold stimulation of radiolabeling when glucose in the labeling medium was increased from 3 to 18 mM, in contrast to a 2.5-fold enhancement of label incorporation into total islet proteins. This 65-kDa protein is evident after 30 min of labeling with 18 mM glucose and is preferentially synthesized compared to its nearest neighbors after both 30 and 60 min of labeling. Glucose induction of the 65-kDa protein was virtually blocked by D-mannoheptulose. Glucose induction of this 65-kDa protein is in practically all aspects comparable to glucose induction of insulin and glucokinase in pancreatic beta cells. A working hypothesis is developed proposing that glucose-response proteins or "glucospondins" are pivotal constituents of pancreatic islet cells and that their discovery and exploration promise new insights into normal and pathological islet cell function. PMID- 2196570 TI - Protein database searches for multiple alignments. AB - Protein database searches frequently can reveal biologically significant sequence relationships useful in understanding structure and function. Weak but meaningful sequence patterns can be obscured, however, by other similarities due only to chance. By searching a database for multiple as opposed to pairwise alignments, distant relationships are much more easily distinguished from background noise. Recent statistical results permit the power of this approach to be analyzed. Given a typical query sequence, an algorithm described here permits the current protein database to be searched for three-sequence alignments in less than 4 min. Such searches have revealed a variety of subtle relationships that pairwise search methods would be unable to detect. PMID- 2196571 TI - Guanosine 3'-diphosphate 5'-diphosphate is not required for growth rate-dependent control of rRNA synthesis in Escherichia coli. AB - rRNA synthesis in Escherichia coli is subject to at least two regulation systems, growth rate-dependent control and stringent control. The inverse correlation between rRNA synthesis rates and guanosine 3'-diphosphate 5'-diphosphate (ppGpp) levels under various physiological conditions has led to the supposition that ppGpp is the mediator of both control mechanisms by inhibiting transcription from rrn P1 promoters. Recently, relA- spoT- strains have been constructed in which both ppGpp synthesis pathways most likely have been removed (M. Cashel, personal communication). We have confirmed that such strains produce no detectable ppGpp and therefore offer a direct means for testing the involvement of ppGpp in the regulation of rRNA synthesis in vivo. Stringent control was determined by measurement of rRNA synthesis after amino acid starvation, while growth rate control was determined by measurement of rRNA synthesis under different nutritional conditions. As expected, the relA- spoT- strain is relaxed for stringent control. However, growth rate-dependent regulation is unimpaired. These results indicate that growth rate regulation can occur in the absence of ppGpp and imply that ppGpp is not the mediator, or at least is not the sole mediator, of growth rate-dependent control. Therefore, growth rate-dependent control and stringent control may utilize different mechanisms for regulating stable RNA synthesis. PMID- 2196572 TI - Isolation of mutants of human immunodeficiency virus protease based on the toxicity of the enzyme in Escherichia coli. AB - The protease encoded by the pol gene of human immunodeficiency virus was expressed in Escherichia coli and found to be toxic to strain BL21(DE3). This toxicity provided a convenient selection for isolating mutants of the protease that are nontoxic and enzymatically inactive. This strong correlation between functional protease and toxicity resulted in rapid identification of several protease mutations, including mutations that exhibit temperature sensitivity. A total of 24 missense mutations and 7 nonsense mutations were identified. The described selection procedure may have wider applications for isolating mutants of other eukaryotic proteins that exhibit a toxic phenotype in E. coli. PMID- 2196573 TI - The role of cell proliferation in chemical carcinogenesis. PMID- 2196574 TI - Cell proliferation and promotion in the hepatocarcinogenicity of peroxisome proliferating chemicals. PMID- 2196575 TI - A complementation analysis of suppression of tumorigenicity in human tumor cell hybrids. PMID- 2196576 TI - Role of free radicals in tumor promotion and progression by benzoyl peroxide. PMID- 2196577 TI - Changes of gap junctional intercellular communication during multistage carcinogenesis. PMID- 2196578 TI - The role of protein kinase C in signal transduction and cellular transformation. PMID- 2196579 TI - Malignant transformation of human fibroblasts by oncogene transfection or carcinogen treatment. AB - Exposure to chemical carcinogens or radiation is considered to cause most human cancer, but human cells in culture have not been successfully transformed to malignancy by such agents. Malignant transformation is a multi-step process and one explanation for the failure to induce such transformation of human cells in culture could be inability to recognize the phenotypes of carcinogen-treated cells that have undergone intermediate changes, so that these cells can be isolated and exposed a second time to cause further changes. To identify possible intermediates, we transfected diploid human fibroblasts with oncogenes known to be active in cells derived from fibrosarcomas and determined the phenotypes produced. H- or N-ras oncogenes flanked by suitable enhancer and promoter sequences caused the cells to exhibit several characteristics of malignant cells, but not to acquire an infinite life span or form tumors. Transfection of these oncogenes in the same constructions, or a viral K-ras oncogene, into an infinite life span, near-diploid, non-tumorigenic cell strain developed in this laboratory (MSU-1.1 cells) resulted in distinct foci of morphologically-altered, anchorage independent, and growth factor independent cells that formed progressively growing, invasive malignant sarcomas in athymic mice and expressed the p21s of the transfected ras genes. Transfection of two other infinite life span human cell lines with the H-ras oncogene in the same construction also yielded malignant cells. Recently, we succeeded in inducing the malignant state in MSU 1.1 cells using carcinogen identified that are one step removed from malignant transformation, others that are two-steps removed, etc. Furthermore, we know what new phenotypes these cells need to express to be malignantly transformed and which oncogenes can make such a change. If, as suggested above, proto-oncogenes are the cellular targets for carcinogen attack, it should be possible, by carcinogen treatment to bring about the malignant state. We have recently succeeded in achieving just such transformation by exposing MSU-1.1 cells to chemical carcinogens. PMID- 2196580 TI - Immortalization as an endpoint in studies on malignant transformation. PMID- 2196581 TI - Tumor suppression studies of human lung cancer. PMID- 2196582 TI - Carcinogenic potency and interspecies extrapolation. PMID- 2196583 TI - Sequence analysis of Salmonella typhimurium revertants. PMID- 2196584 TI - Leukemogenic risk prediction of the cytostatic treatment. PMID- 2196585 TI - Promotion and progression in carcinogenesis. PMID- 2196586 TI - Role of altered hepatic foci in the stages of carcinogenesis. PMID- 2196587 TI - Physiological methylation in carcinogenesis. PMID- 2196589 TI - [Synthetic drugs of abuse, the second generation (designer drugs). 1. Amphetamine and other arylalkane amines]. PMID- 2196588 TI - [Lethal therapy of leukemia. The role of methyltransferases in the administration of thiopurines]. PMID- 2196590 TI - Human recombinant interleukin-2 as an experimental therapeutic. PMID- 2196591 TI - Plants and men in space. A new field in plant physiology. PMID- 2196592 TI - Hemodynamic, plasma renin activity and norepinephrine changes induced by anti-G suit inflation in man. PMID- 2196593 TI - Cardiovascular responses to sustained acceleration. PMID- 2196594 TI - Physiologic bases for increased G-level and G-duration tolerances. PMID- 2196595 TI - The effect of external inspiratory resistance to breathing on man's orthostatic tolerance. PMID- 2196597 TI - A mathematical modeling of the cerebrovascular system. PMID- 2196596 TI - G-induced loss of consciousness detection limits with transcranial Doppler monitoring. PMID- 2196598 TI - Ultrasound technology and space cardio-vascular medicine. PMID- 2196599 TI - Metabolic consequences of fluid shifts induced by microgravity. PMID- 2196600 TI - Cardiovascular deconditioning during weightlessness simulation and the use of lower body negative pressure as a countermeasure to orthostatic intolerance. PMID- 2196601 TI - Destructive and adaptive processes in human vertebral column under altered gravitational potential. PMID- 2196602 TI - Gravity, calcium, and bone: update, 1989. PMID- 2196603 TI - Toward an univocous interpretation of cardiovascular biomechanics in hyper and microgravity. PMID- 2196604 TI - Bone cellular effects after weightlessness exposure--an hypothesis. PMID- 2196605 TI - Competing antagonists to energy production in space and their effect on calcium metabolism. PMID- 2196606 TI - Disorders of the external ear. AB - External ear disorders are diffuse, varying from cosmetically unacceptable anomalies to serious neoplasms. Between these extremes lie the more common problems presenting to the primary care physician in an ambulatory setting. These problems include trauma, obstructions, dermatoses, and infections, some or all of which may be vexing to the busy clinician. Most of these problems are not serious and can be approached with the confidence of a salutary outcome with appropriate therapy. PMID- 2196607 TI - Immitance audiometry. AB - Immitance audiometry is a safe, simple, reliable, and relatively objective method of determining middle-ear function that provides advantages for examining the difficult patient because minimal cooperation is needed. Acoustic-immitance measurements obtain sophisticated data that give us valuable information about the middle ear mechanism as a whole. It can be used in a quiet office environment. Immitance audiometry can confirm a doubtful otoscopic diagnosis and screen for ear disease. There are limitations to observer reliability with otoscopy, which has good sensitivity but poor specificity, in contrast to immitance audiometry. The tympanogram can be classified into four different patterns on the basis of its characteristics. These patterns are diagnostic, distinguishing normal function from various types of middle ear pathology. Immitance audiometry has very high sensitivity and specificity. The acoustic reflex, a contraction of the stapedius muscle following an intense auditory stimulus, can be valuable in determining a conductive hearing loss and many other otologic diagnoses. As a screening tool, immitance audiometry is most valuable in populations at risk for middle ear effusion, primarily those aged 7 months to 5 years. Significant improvements in measurements of ear function also allow us to be more precise in the diagnoses of otosclerosis, perforation of the tympanic membrane, ossicular discontinuity, facial nerve dysfunction, and brain stem disorders. PMID- 2196609 TI - Otitis media. AB - Otitis media, one of the most common problems encountered in the care of children, remains fraught with controversy on the most appropriate methods of management. A proliferation of effective antimicrobial regimens has kept pace with emergence of resistant strains of pathogens, and sufficient information now exists to guide the clinician in making logical therapeutic decisions. Recommendations are given on appropriate use of terminology, diagnostic procedures, and therapeutic interventions for the various phases of otitis media. PMID- 2196608 TI - Adult hearing loss. AB - Identification and evaluation of adult hearing loss is an important task for primary care physicians. Recent studies reporting the reliability and validity of simple testing instruments reinforce this conclusion. Although most cases will be secondary to noise exposure or age-related and benefit from amplification, a diligent search for more unusual causes, some of which have specific curative therapy, is always needed. The initial prescription and fitting of hearing aids is the realm of the audiologist. The primary care physician can enhance the treatment program by providing global evaluation, educating the patient as to likely therapy and realistic expectations of results, and providing long-term follow-up and functional assessment of hearing aid use. The burden of hearing loss is particularly heavy in the nursing home population. In this arena, the physician can ease the burden by being attentive to the possibility of hearing loss causing unexpected behavior, searching for, and when possible, treating reversible causes, and using assistive devices and behavioral techniques to enhance communication when the hearing impairment cannot be corrected. PMID- 2196610 TI - Tinnitus. AB - Sound without external stimuli may warn of serious conditions. Accurate history and physical examination along with ancillary testing, including audiograms, are essential in evaluation of these patients. Evaluation of sudden tinnitus may save hearing. Extra-auditory tinnitus may arise from respiratory, vascular, and muscular sources that are often treatable. Conductive tinnitus may indicate treatable malformation of the external or middle ear. Sensorineural tinnitus may be drug-related, noise-related, of central origin, or due to cochlear deterioration. Comprehensive diagnostic procedures can be followed by medical, surgical, psychologic, or masking therapies. All patients with tinnitus can benefit from patient education and preventive measures, and oftentimes the physician's reassurance and assistance with the psychologic aftereffects of tinnitus can be the therapy most valuable to the patient. PMID- 2196611 TI - Dizziness. AB - In evaluating a patient with dizziness, the history remains the main source of information for diagnosis. Peripheral labyrinthine abnormalities are responsible for the majority of vertiginous symptoms. These disorders may be multifactorially caused or secondary to trauma and inflammation. Diagnostic testing may be of some assistance in corroborating a diagnosis. Medical therapy and dietary restrictions remain the main treatment modalities along with physical rehabilitation. In some patients, however, surgical intervention is indicated. PMID- 2196612 TI - Rhinitis. AB - While it is a common problem, the differential considerations and treatment options can make the appropriate diagnosis and management of rhinitis a challenge. Frequent causes include the viral URI, allergic rhinitis, and vasomotor rhinitis. Eosinophilic nonallergic rhinitis is an interesting syndrome that must be considered in the patient whose presentation is suggestive of allergy but whose laboratory investigation is unrewarding for the same. Rhinitis medicamentosa is a distressing problem that is best managed by prevention. A careful history, physical examination, prudent clinical testing, and appropriate consultation will be beneficial to the primary care physician and allow management of most of these diseases in the ambulatory setting. PMID- 2196613 TI - Sinusitis. AB - Early and aggressive treatment of allergic, inflammatory, and infectious diseases of the nose and paranasal sinuses should reduce the potential for chronic and irreversible disease of the sinus mucosa. Identification of underlying allergies, reactive mucosa, impaired mucosal transport, anatomic obstruction, or narrowing are key elements in establishing an effective treatment plan and the ultimate resolution of these disease processes. PMID- 2196614 TI - Pharyngitis, croup, and epiglottitis. AB - The exact diagnosis of pharyngitis remains a problem despite the advent of rapid streptococcal screening. An apparent resurgence of rheumatic fever outbreaks makes it more important to attempt to accurately diagnose pharyngitis. Positive identification of streptococci should be followed by treatment with penicillin, or erythromycin in the patient with penicillin allergy. The patient without positive identification of streptococci will need either observation or further evaluation depending on the degree of illness. Classic croup or laryngotracheobronchitis is a clinical entity that can be diagnosed with reasonable confidence. The few patients that require hospitalization can be treated with humidity, racemic epinephrine, corticosteroids, parental and child support, or any combination of these with good results. Continued observation of all patients with croup is necessary to recognize the uncommon complication of bacterial tracheitis when it occurs. Epiglottitis has a varied clinical appearance and management according to age groups. Infants show a mixed clinical picture similar to croup, but with more obstruction. The classic epiglottitis with acute airway obstruction is seen in the 3-8-year-old age group. Adults have a less fulminant form of supraglottitis. Infants and children will need artificial airway management in most cases, whereas many adults can be treated simply with observation. PMID- 2196615 TI - Hoarseness. AB - The symptom of hoarseness is one with many causes and several treatments. It is the abnormal production of sound, perceived as raspiness, breathiness, harshness, vocal tension, or lower pitched voice. Whether the patient notices vocal fatigue or says that it's harder to talk with a worsening voice as the day progresses, the underlying cause of the hoarseness must be found. Only then can the hoarseness or the disease leading to it be treated competently to bring the patient and the voice back to health. PMID- 2196616 TI - Common problems of the oral cavity. AB - The oral cavity is an area of the human body that is often given only cursory surveillance by primary care physicians. In this article, I have discussed a comprehensive approach for collecting subjective and objective data from the patient that is pertinent to oral conditions. Most common and critical problems have been reviewed in detail, focusing on their definition, epidemiology, pathophysiology, clinical manifestations, diagnosis, and management. This review is intended to sensitize physicians to the need to evaluate oral complaints more completely, to diagnose them more accurately, and to treat them more successfully. PMID- 2196617 TI - Disorders of the salivary glands. AB - A careful history and physical examination is essential in diagnosing and treating salivary gland disorders. This alone may identify congenital lesions, trauma, acute and chronic inflammatory diseases, and a variety of other conditions affecting the salivary glands. The most common presenting complaint is that of a lump in a salivary gland, and the onus is on the physician to prove the presence or absence of malignancy. Laboratory and radiographic studies are of minimum value in making this distinction, and biopsy, under general anesthesia, by a competent head and neck surgeon with microscopic evaluation is often necessary. Office biopsy or large or fine-needle aspiration should not be attempted. Fortunately, most neoplasms are benign, and many malignant forms are low grade and have a good prognosis. PMID- 2196618 TI - Evaluation of masses in the neck. AB - A mass in the neck represents a diverse number of possible pathologic conditions. The importance of obtaining a thorough history and ensuring that a complete head and neck examination is performed has been emphasized. The physician should then be able to determine if the mass is insignificant and warrants observation or significant and warrants action. Physicians must determine, to the best of their abilities, that appropriate evaluation and treatment are done for the patient. Common errors should be avoided. PMID- 2196619 TI - Facial nerve paralysis. AB - Bell's palsy, an idiopathic facial nerve palsy, is the most common cause for acute facial nerve paralysis. Bell's palsy is not synonymous with facial nerve paralysis but is a diagnosis of exclusion for acute onset of idiopathic facial nerve paralysis. The differential diagnosis for facial nerve paralysis should be considered to correctly evaluate and give appropriate therapy in a timely fashion for the treatable causes of facial nerve paralysis. The status of facial nerve paralysis should be monitored by repeat electrical examinations, preferably ENoG. Most importantly, no one treatment is appropriate for all patients with facial nerve paralysis. PMID- 2196620 TI - Phenelzine and atenolol in social phobia. AB - Seventy-four patients meeting DSM-III criteria for social phobia completed 4 or more weeks of double-blind, randomized treatment with the monoamine oxidase inhibitor phenelzine, the cardioselective beta-adrenergic blocker atenolol, or placebo. Sixty-four percent of the patients on phenelzine demonstrated moderate or marked improvement, compared to 30 percent on atenolol and 23 percent on placebo. Phenelzine was significantly more effective than atenolol or placebo, whereas the efficacy of atenolol and placebo did not differ significantly. Patients were also prospectively divided into generalized and discrete subtypes of social phobia. Phenelzine appeared to be a particularly effective treatment for the generalized form of social phobia. Atenolol may be useful for discrete forms of social phobia such as performance anxiety. PMID- 2196621 TI - Naltrexone in autistic children: a double-blind and placebo-controlled study. AB - A double-blind, placebo-controlled study was designed to assess critically the effects of naltrexone on behavioral symptoms and learning in autistic children, and its safety. This is a preliminary report on 18 children, ages 3.08 to 7.99 years, who completed this ongoing study. Subjects were randomly assigned to naltrexone or placebo and received daily doses over a period of 21 days. Naltrexone was superior to placebo according to blind Clinical Global Consensus Ratings (unpublished scale). However, other behavioral rating measures did not confirm this result. There was only a suggestion that naltrexone reduced fidgety and hyperactive behavior and tended to alleviate overall symptomatology in older children. Naltrexone did not appear to affect discrimination learning. Results are preliminary and, owing to the small sample size, can be considered only suggestive until this study is completed or replication is obtained from independent research. PMID- 2196622 TI - Placebo-controlled dose-ranging trial designs in phase II development of nefazodone. AB - Nefazodone is a selective 5-HT2 receptor antagonist. Nefazodone has a pharmacologic profile similar to trazodone and other phenylpiperazine antidepressants, but distinct from nonselective first-generation agents and other selectively acting second-generation agents. Results of a multicenter, double blind, fixed-dose trial indicate nefazodone is effective in improving depressive symptoms of outpatients with major depressive disorder treated with daily doses of 100 mg to 200 mg. A comparison of the fixed-dose trial design with an alternative design permitting dose titration within fixed ranges is presented. The relative merits of each design for establishing therapeutic dose ranges are discussed. PMID- 2196623 TI - Fluoxetine: relationships among dose, response, adverse events, and plasma concentrations in the treatment of depression. AB - Data from two large, fixed-dose trials support the efficacy of a fixed 20 mg/day dose of fluoxetine in the treatment of depression. Data pooled from these two studies suggest a dose relationship for adverse events during fluoxetine therapy. At a fixed 20 mg/day dose, only nausea and insomnia were reported by a significantly greater percentage of patients (p less than .05) than those treated with placebo. However, at 60 mg/day, nausea, anxiety, dizziness, and insomnia were reported by a significantly greater percentage of patients (p less than .05) than those treated with placebo. The potential relationship of response rate [Hamilton Rating Scale for Depression (HAM-D) total decrease greater than or equal to 50%] to plasma concentrations of fluoxetine, norfluoxetine, and fluoxetine plus norfluoxetine was evaluated in one study which excluded early responders (less than or equal to 3 weeks of therapy). No significant relationship was found. Furthermore, adverse events were not related to plasma concentrations. PMID- 2196624 TI - Anticonvulsants in affective disorders. AB - The current status of anticonvulsant drugs compared to other treatments for the management of affective disorders is evaluated. Data from controlled studies suggest that carbamazepine is superior to placebo, equivalent to neuroleptics, and comparable to lithium for mania, at least in relatively treatment-refractory patients. Carbamazepine may also be useful as an antidepressant and for prophylaxis. Valproate and clonazepam show promise in the treatment of mania and for prophylaxis, but the number of patients studied in controlled trials is small. Lorazepam and other benzodiazepines may be useful antimanic agents, and alprazolam exerts antidepressant effects, although its efficacy relative to the tricyclics is unclear. Electroconvulsive therapy (ECT) is effective for both mania and depression. Established treatments are carbamazepine and ECT for mania and ECT for depression. Still experimental are valproate and clonazepam for mania; carbamazepine and alprazolam for depression; and carbamazepine, ECT, valproate, and clonazepam for maintenance. Combinations with lithium appear promising but await double-blind trials. The place of other anticonvulsants in the treatment of affective disorders is unknown. PMID- 2196625 TI - Treatment of rapid cycling bipolar illness. AB - Rapid cycling patients (greater than or equal to 4 episodes/year) often show inadequate response to lithium carbonate and are vulnerable to antidepressant induced switches or cycle acceleration. Treatment with the anticonvulsant carbamazepine is now an accepted adjunct or alternative, and a series of uncontrolled studies also suggest the utility of valproate in this patient population. Clonazepam, suppressive doses of thyroid, calcium channel blockers, and other innovative treatments appear promising and deserve careful clinical investigation. PMID- 2196626 TI - New issues in the prediction of antidepressant response. AB - Over the past three decades, certain clinical factors have been identified as either positive or negative predictors of response to treatment with the tricyclic antidepressants (TCAs), and have been well reviewed in the psychopharmacology literature. The current report is an effort to focus attention on methodologic and clinical issues that have recently been given attention in this area and that may be useful to clinicians and researchers. The specific issues addressed are (a) the implications of the definitions of "response" in studies of predictive factors, (b) the importance of compliance with treatment, (c) the potentially confounding issues of severity of illness and psychoticism in depression, (d) the status of chronicity of illness as a factor in prediction of treatment response, and (e) the possible value of a definition of "atypical depression" for differential selection of treatment. PMID- 2196627 TI - Clinical predictors of treatment response in obsessive compulsive disorder: exploratory analyses from multicenter trials of clomipramine. AB - Two multicenter, double-blind trials were conducted in adults with DSM-III (American Psychiatric Association 1980) defined Obsessive Compulsive Disorder (OCD), comparing clomipramine (Anafranil, CMI) up to 300 mg daily with placebo. Of 519 patients evaluated, 260 received CMI for up to 10 weeks. More than half of the CMI treated patients were significantly improved, approximately 30 percent were minimally improved, and 15 percent showed no improvement after CMI treatment. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was used to assess treatment effects and attempts were made to correlate change in Y-BOCS score from baseline with a number of baseline characteristics, including age, sex, duration of OCD, baseline Y-BOCS score, baseline Hamilton Rating Scale for Depression (HAM D) score, presence or absence of secondary depression, and predominance of obsessions or compulsions. Pearson and/or Spearman correlations failed to reveal any statistically significant correlations between outcome and any of the baseline characteristics studied. While the differences were not statistically significant, it did appear that male patients and patients with a longer duration of illness may be less likely to respond to CMI treatment; however, the overall conclusion from this analysis is that none of the variables studied is a reliable predictor of responses to treatment with CMI. PMID- 2196628 TI - Current pharmacotherapies for opioid dependence. AB - Pharmacotherapy of intravenous opioid abusers has taken on increased urgency with the acquired immunodeficiency syndrome (AIDS) epidemic, because in major cities intravenous drug abuse now accounts for half of new AIDS cases. The pharmacotherapy of acute dependence and withdrawal has benefited from the use of clonidine, particularly in combination with antagonist-precipitated withdrawal. However, protracted abstinence and its associated risk of relapse to drug abuse has underscored the need for maintenance pharmacotherapies. Maintenance pharmacotherapies such as methadone and naltrexone are frequently needed to sustain outpatient retention and abstinence from heroin. Methadone is more widely used than is naltrexone, an oral, long acting heroin blocker that can maintain drug abstinence after detoxification. Because of limitations in both of these maintenance agents, two investigational maintenance treatments have been tested: levo-alpha-acetylmethadol (LAAM), a long-acting form of methadone, and buprenorphine, a long-acting mixed opioid agonist-antagonist with properties similar to either methadone or naltrexone, depending on dose. Clinical use, limitations, and outcome with each medication are reviewed. PMID- 2196629 TI - Pharmacotherapy of adolescent major depression: beyond TCAs. AB - To date, controlled studies of tricyclic antidepressant (TCA) treatment of adolescent major depression have failed to demonstrate efficacy of these compounds despite multiple lines of evidence suggesting that adolescent major depression is related to the adult form of the disorder. One possible means of increasing the power of such studies is explored: examination of the pattern of response to medication and separation of placebo responders from medication responders using the technique proposed by Quitkin and colleagues (1984). Open label studies of nontricyclic antidepressant agents in adolescents are reviewed, and suggestions are made for future pharmacological trials in this population. PMID- 2196630 TI - The pharmacotherapy of depressive illness in adolescence: I. An open label trial of imipramine. AB - The efficacy of imipramine hydrochloride (IMI) for adolescents with major depressive illness meeting Research Diagnostic Criteria (RDC) and DSM-III criteria was assessed in an open-label trial of 35 inpatients. Patients were treated for 6 weeks up to a target dosage of 5 mg/kg/day and assessed weekly by the Hamilton Rating Scale for Depression (HAM-D) and Clinical Global Impressions Improvement scale (CGI). A total of 34 patients in the sample completed the trial, 28 achieving the full target dosage (mean = 222 mg; mean IMI plus desmethylimipramine (DMI) plasma level = 237 ng/ml). Among 24 nondelusional patients, only one third were considered responders based on pattern analysis of the time of onset and persistence of symptom reduction. Among 10 delusional patients, the response rate was 10 percent. Although total IMI plus DMI plasma level did not differ between responders and nonresponders, no responder had a level below 180 ng/ml. In univariate linear regression analysis, no single variable was predictive of response status at 6 weeks. These findings underscore the importance of a comprehensive study of the potency of antidepressant compounds in adolescents and the need for further investigation of psychobiological process mediating drug effects. PMID- 2196631 TI - Double-blind placebo-controlled study of nortriptyline in depressed adolescents using a "fixed plasma level" design. AB - We performed a random assignment, double-blind, placebo-controlled study of nortriptyline (NT) in postpubertal 12- to 17-year-olds with Research Diagnostic Criteria (RDC) and DSM-III major depressive disorder. The protocol included a 2 week placebo washout phase and an 8-week double-blind, placebo-controlled phase with weekly plasma level monitoring. Active subjects had their plasma level placed at 80 +/- 20 ng/ml by using previously developed tables to determine the starting dose from a plasma level drawn 24 hours after a single dose administered at baseline. The study population was severely depressed and had a chronic, unremitting course prior to study; a high percentage of family histories with affective disorder, alcoholism, and suicidality; and a high rate of comorbidity. Of the 52 subjects enrolled, there were 17 placebo washout responders, 4 dropouts, and 31 completers (12 active and 19 placebo). Only one active subject responded; therefore, the study was terminated early. The mean NT plasma level was 91.1 (18.3 SD) ng/ml. The two treatment groups had similar postprotocol severity ratings. Subjects on active drug did not evidence the anticholinergic side effects reported in adult samples. The negative outcome in this study is similar to the findings in our previously reported NT study in prepubertal 6- to 12-year-olds. PMID- 2196632 TI - Heavy ion effects on yeast: inhibition of ribosomal RNA synthesis. AB - Diploid wild-type yeast cells were exposed to beams of heavy ions covering a wide range of linear energy transfer (LET) (43-13,700 keV/microns). Synthesis of ribosomal RNA (rRNA) was assessed as a functional measure of damage produced by particle radiation. An exponential decrease of relative rRNA synthesis with particle fluence was demonstrated in all cases. The inactivation cross sections derived were found to increase with LET over the entire range of LET studied. The corresponding values for relative biological effectiveness were slightly less than unity. Maximum cross sections measured were close to 1 micron 2, implying that some larger structure within the yeast nucleus (e.g., the nucleolus) might represent the target for an impairment of synthetic activity by very heavy ions rather than the genes coding for rRNA. Where tested, an oxygen effect for rRNA synthesis could not be demonstrated. PMID- 2196633 TI - [The proteinase activity in the cell nuclei of rats following exposure to gamma radiation and methylnitrosourea]. AB - Activity of nuclear proteinases in blood and liver cells of rats exposed to whole body gamma-irradiation (10 Gy) has been comparatively studied by the capacity of splitting the casein substrate. Proteinase activity in nuclei of irradiated rat leukocytes was shown to increase by 2.5 times and to gradually decrease after 48 h reaching 150-160% as compared to the control. Two hours following a single injection of methyl nitrosourea the alteration in the activity of proteinases in nuclei of rat hepatocytes and leukocytes was different from the alteration of this index after gamma-irradiation. PMID- 2196634 TI - Formaldehyde in drinking water: comparative hazard evaluation and an approach to regulation. AB - Formaldehyde, a widely used industrial chemical to which humans are ubiquitously exposed, presented cause for concern when it was demonstrated to be carcinogenic in laboratory animals. Risk assessment protocols subsequently applied to formaldehyde are of questionable validity in light of the results of recent mechanistic investigations of biological responses to formaldehyde. Further, the hazard of ingested formaldehyde is not addressed in current assessment protocols. This paper addresses the potential human health risks accompanying low-level exposure to formaldehyde as a contaminant in drinking water. In this exposure scenario, noncarcinogenic risk from inhalation of formaldehyde from drinking water is evaluated through knowledge of the metabolism and biological effects of formaldehyde exposure. Noncarcinogenic risk from ingestion of formaldehyde in drinking water is evaluated from the perspective gained by comparison with dietary sources of formaldehyde. Carcinogenic risk to humans is evaluated in light of recent investigations into the mechanisms underlying biological responses to formaldehyde exposure. Finally, based on a comparison of ingestion of formaldehyde in drinking water with ingestion of naturally occurring formaldehyde in foods, a comparative hazard approach to formaldehyde regulation is offered as a supplement to the rigid evaluation protocols currently used. PMID- 2196635 TI - Literature-derived absorption coefficients for 39 chemicals via oral and inhalation routes of exposure. AB - Absorption refers to the amount of a chemical or substance that is able to cross biological membranes and be taken up by the blood for subsequent distribution to target tissues. The term absorption coefficient, as used here, is a numerical descriptor characterizing that fractional uptake by the blood and represents an approximation of the biological "dose" ultimately responsible for toxicity or other effects following exposure or chemical administration. Regulatory agencies utilize absorption coefficients in deriving acceptable daily intake values and health advisory indices, as well as in quantifying radiological risk. However, absorption coefficients do not exist for many chemicals due to a paucity of appropriate toxicological data. As a result, regulatory policy must often provide default options that assume, for example, 100% absorption by all routes to permit evaluation of "data-gap" chemicals. This paper attempts to improve the situation by providing a discrete source of route-specific absorption coefficients that are based on experimental data reported in the open literature. The estimates presented here are the result of an extensive investigation of three data bases (TOXLINE, HSDB, and CIS), many agency documents, and nearly 200 articles from 30 scientific journals. Acknowledging that absorption efficiency varies with dietary status, age, and several other situation-specific factors, the estimates presented here are intended to reflect absorption by the average adult human. PMID- 2196636 TI - Trends in centralized control of the executive branch. AB - One purpose of this essay is to review the major federal regulatory accomplishments and shortfalls in the area of health and safety and to assess where we are headed in order to suggest desirable directions for regulatory reform. The thesis of this paper is that the most persistent, conspicuous, and pervasive effect on regulation today has been centralization, which broadly denotes the expansion of federal executive responsibilities, primarily at the presidential level, and extensive governmental rules. The author posits that this trend has moved through three notable stages. First, President Franklin Delano Roosevelt created a paradigm for centralization within the executive branch of the federal government to enlarge the position of the national government in regulating American life as he confronted broadened domestic and foreign responsibilities. Second, there was a long span from Truman's stewardship to that of Carter, characterized by ensconcement of, and accretions to, FDR's model and by an acceptance of the vastly augmented role of the federal government in American society. Third, President Reagan carried centralization to its furthest point yet, structurally and managerially, but for a different ultimate purpose: a reversal of a nearly half-century tradition--a deregulation of the federal government's position in American's economic life while increasing it in the areas of national defense, internal security, and personal morality. In the conclusion the writer contends that the precedent of Mr. Reagan's centralizing efforts will weigh heavily on his successors as they seek either to perpetuate his priorities or to magnify the national government in a fourth stage. PMID- 2196637 TI - Analysis of OSHA's short-term-exposure limit for benzene. AB - A review of the data cited by OSHA in its final standard for exposure to benzene provides no clear scientific basis for a short-term-exposure limit (STEL). While leukemia and bone marrow toxicity were related to cumulative exposures of benzene received by workers, no evidence was presented that the rate of exposure at a given cumulative exposure contributed to the effects. Likewise, animal experiments suggested that exposures of several hours duration at a given level of benzene induced more bone-marrow toxicity when administered 3 rather than 5 days/week but did not indicate that the rate of exposure over shorter time scales played any role. The toxicokinetics of benzene in humans were also studied to determine whether nonlinear dose-rate effects would be likely to result from peak exposures associated with an exposure dose of 8 ppm-hr, which is allowed under the permissible exposure limit. This led to three conclusions. First, the concentration of benzene in the bone marrow should be sufficiently damped that the impact of a peak exposure should be minimal. Second, the peak concentration of benzene in the liver should be within the capacity of the cytochrome P450 system to maintain first-order metabolism. And finally, the maximum blood concentration of metabolites should be well below levels which have been shown to induce toxic effects in vitro. Taken together, the toxicokinetic relationships and the absence of clear experimental dose-rate effects suggest that the current STEL for benzene is unwarranted, assuming that 8-hr average exposures are kept below 1 ppm. While the argument can be made, on the basis of health considerations, that the existing 8-hr limit for benzene is too high, the rate of exposure during short periods appears to be irrelevant. Thus, we recommend that health professionals focus upon long-term exposures to benzene received by large numbers of workers rather than devote scarce resources to evaluate transient air levels. PMID- 2196638 TI - The importance of pharmacokinetic and receptor studies in drug safety evaluation. AB - The importance of pharmacokinetic and receptor studies in the preclinical and clinical safety evaluation of candidate drugs is reviewed with reference to a number of recently developed drugs. Different aspects of the relationships between pathways of metabolism, pharmacokinetics, receptor interactions, and drug toxicity are illustrated. The failure of animal toxicity studies to predict drug toxicity in humans, due to species differences in metabolism and pharmacokinetics, is illustrated by reference to the anti-inflammatory antiviral terpenoid carbenoxolone, the antiasthmatic candidate drug FPL 52757, and the cardiotonic drug amrinone. The false prediction of adverse effects in man from toxicity manifested in experimental animals, due to species differences in pharmacokinetics or receptor activities, is exemplified with reference to the antiepileptic valproic acid, the hypolipidemic drug ciprofibrate, the antipeptic ulcer drug, omeprazole, and the progestogen lynestrenol. Finally, the importance of adequate, repeat-dose, clinical pharmacokinetic studies in patients as distinct from healthy volunteers to evaluate any effect of the disease state, in the elderly and the young to examine the effects of age, and in sufficiently large populations to detect genetic anomalies and idiosyncrasies is illustrated by reference to the anti-rheumatoid drug benoxaprofen, the antiangina drug perhexiline, and the diuretic tienilic acid. PMID- 2196639 TI - A new approach to deriving community exposure guidelines from "no-observed adverse-effect levels". PMID- 2196640 TI - Management of massive haemoptysis. PMID- 2196641 TI - Catamenial haemoptysis from endobronchial endometriosis--a case report and review of previously reported cases. PMID- 2196642 TI - Empyema thoracis: what is the role of surgery? PMID- 2196643 TI - [Measurement of airway resistance by an interrupter technique in anesthetized dogs during methacholine induced bronchoconstriction]. AB - Airway resistance was measured by an interrupter technique in anesthetized and paralyzed dogs. Bronchoconstriction was then induced by the inhalation of methacholine hydrochloride at a concentration of 25 or 50 mg . ml-1 for ten minutes. Airway resistance was measured again immediately after the inhalation of methacholine and 50 minutes later. Under normal conditions, airway resistance increased with a linear relationship to the expiratory airflow as expressed by a function of Y = K1 + K2X. K1 and K2 were calculated by a least square method. As a result, K1 increased markedly immediately after the inhalation of methacholine and returned to the control level thereafter. However, it was still higher than the control 50 minutes later. On the other hand, no statistically significant changes were observed because the changes in K2 were variable. In some cases, K2 increased, while in others it was unchanged. K2 decreased in more cases, however, and a negative value was often seen. This inverse correlation between flow and resistance was supposed to reflect the occurrence of small airway obstructions during the end expiratory phase. Therefore, it was considered that this method is capable of detecting small airway abnormalities which could not be detected by %FEV1.0. PMID- 2196644 TI - Pathophysiology of hepatic encephalopathy. PMID- 2196645 TI - Medical management of animals with portosystemic shunts. PMID- 2196646 TI - Diagnostic imaging of portosystemic shunts. PMID- 2196647 TI - Surgical management of extrahepatic portosystemic shunts in the dog and cat. PMID- 2196648 TI - The anatomy and embryology of portosystemic shunts in dogs and cats. PMID- 2196649 TI - Historical, physical examination, and clinicopathologic features of portosystemic vascular anomalies in the dog and cat. PMID- 2196650 TI - Liver function tests in the diagnosis of portosystemic vascular anomalies. PMID- 2196651 TI - [Molecular and diagnostic genetics]. AB - Using the recent developments of molecular biology techniques, our laboratory is offering carrier and prenatal diagnosis for a variety of genetic disorders including cystic fibrosis, phenylketonuria, thalassaemia alpha and beta, sickle cell anaemia, myotonic dystrophy, von Recklinghausen's disease, autosomal polycystic kidney disease, haemophilia A and B, Martin-Bell syndrome (fragile X), Becker and Duchenne muscular dystrophy, etc. It is likely that the rapid advances made in the establishment of the human genetic map will considerably expand the spectrum of diseases for which diagnosis by molecular genetics will become available. PMID- 2196652 TI - [Should certain carotid artery stenoses be surgically treated?]. AB - Carotid endarterectomy is controverted. We present the available data and endeavour to answer the following questions: 1) what is the probability of morbidity and mortality from ipsilateral cerebral infarction due to asymptomatic or symptomatic extracranial carotid stenosis (transient or prolonged regressive ischaemic strokes) medically treated or untreated? 2) what is the peri-operative morbidity-mortality rate? 3) does the degree of stenosis affect the clinical course? 4) does the presence of ulcerations play a role? 5) what is the long-term probability of ipsilateral cerebral infarction when the stenosis has been operated with success? 6) should endarterectomy be regarded as an effective treatment? and if so, in which cases? Our study of asymptomatic stenoses has shown that the mean peri-operative morbidity-mortality rate was 4.22 percent and the long-term incidence of ipsilateral infarction was 0.34 percent/year for operated stenoses and 0.50 percent/year for all nonoperated stenoses; the latter figure rose to 1.18 percent/year in cases with severe stenosis and to more than 10 percent/year in cases with extensive and irregular ulcerations. In symptomatic stenoses, the cumulative peri-operative morbidity-mortality rate was 5.5 percent. The long-term annual incidence of ipsilateral cerebral infarction was 0.67 percent in patients operated upon and 2.70 percent in patients unoperated upon. A comparison of the natural history of asymptomatic carotid stenoses and of stenoses which were responsible for transient or prolonged regressive ischaemic strokes with the results of surgery showed that endarterectomy is: 1) probably justified in cases with deep and irregular ulcerations with or without symptoms and stenotic or nonstenotic; 2) perhaps justified in cases with symptomatic stenosis without ulcerations. These conclusions should be moderated as they rest on general data and do not take into account a number of factors that are often neglected in the literature, notably the quality of the results obtained by each individual surgeon. PMID- 2196653 TI - [Disorders of voluntary motor activity and lesions of caudate nuclei]. AB - Three clinical cases are reported, resulting in apathy, uninterest, flattened affect and lack of initiative for usual daily activities. Intellectual performances were normal and there was no depression. This syndrome was reversible when patients were stimulated. Stereotyped behaviors resembling compulsions were frequent. One of the patients presented with prolonged akinetic episodes reversible by verbal stimulation. CT and MRI showed bilateral lesions, mainly in and around the head of the caudate nucleus. Such behavioral disorders have been termed psychic akinesia or athymhormia syndrome, suggesting that the patients suffered from a loss of drive and motivation. The lesions involved bilaterally the globus pallidus, the striatum or the frontal lobe. Recently, anatomical findings have shown several circuits through the basal ganglia additional to the motor circuit. The caudate nucleus receives inputs from the prefrontal and limbic cortex. These inputs are transmitted to the globus pallidus, then to the thalamus and ultimately return to the dorsolateral prefrontal, lateral orbitofrontal and anterior cingulate areas. Lesions in any part of these cortico-subcortical loops may be responsible for a dramatic behavioral syndrome, emphasizing their functional specificity in drive. However, a procedural learning impairment in neostriatal dysfunction could possibly explain the disorders observed in our patients. PMID- 2196654 TI - [Internal carotid occlusion and essential thrombocythemia. 2 cases]. AB - We report 2 cases of occlusion of the internal carotid artery in young, non atherosclerotic patients with essential thrombocythemia (ET). This complication of ET seems to be rare, but is probably underdiagnosed since transient ischemia, which is frequent in ET patients, is seldom explored by angiography. The excess of thrombocytes and the thrombopathy may account for the microvascular complications, but in the absence of any other contributory factor, occlusions of large arteries, such as the ICA, is more difficult to explain. PMID- 2196655 TI - [Cerebral necrosis found 13 years after irradiation of osteosarcoma of the cranial vault]. AB - Delayed cerebral radiation necrosis was discovered 13 years after irradiation of the skull for osteosarcoma. Conservative treatment with glucocorticoids is discussed. PMID- 2196656 TI - [Fulminating cryptococcal meningoencephalitis. An anatomo-clinical case]. AB - We report a case of cryptococcal meningoencephalitis in a 52 year-old man. The patient had complained of headache and drowsiness for a few hours before he became comatose with a bilateral sixth cranial nerve palsy. The cerebrospinal fluid contained less than one lymphocyte per cubic millimeter, a low glucose level (0.20 g/l) and numerous Cryptococcus neoformans encapsulated yeasts. A neuropathological study showed that the cortex and midbrain were involved. To our knowledge, such an acute case with death within the first 20 hours has not yet been reported. PMID- 2196657 TI - [When to begin antiepileptic treatment?]. AB - The decision to begin an antiepileptic treatment is not always an easy one, as this treatment will be long lasting with possible side-effects. However, if the patient has had several seizures or if, after a first seizure, there are certain features predicting that other seizures will follow, then in all but very rare cases this decision must be made and applied as soon as possible. Patients who will have chronic epilepsy are recognized within the first two years, and among the factors preventing a therapeutic failure, early treatment is of the utmost importance. After a first, strictly isolated seizure, and for lack of convincing figures as to the risk of recurrence, many data must be examined, the most important being the patient's wish. All this shows that there is room for various decisions. PMID- 2196658 TI - [Stopping antiepileptic treatment]. AB - Antiepileptic drug withdrawal must be considered in seizure-free patients. It is theoretically possible. A seizure relapse is frequent. Numerous factors predictive of relapse are known, but they are of limited value. A favorable outcome depends mainly on the patient's epileptic syndrome. Drug reduction must be carried out stepwise, with a slow dose-tapering. A partial withdrawal: reduction of polytherapy to monotherapy, or reduction in daily doses, can also be wise. PMID- 2196659 TI - [Sarcoidosis and heredity. 3 familial cases]. AB - It is very uncommon to find several cases of sarcoidosis in the same family. In the majority of published reports, only 2 persons are involved in each family. Genetic predisposition is probably, but its true importance as compared with environmental conditions is uncertain owing to the lack of epidemiology studies. We report 3 cases of sarcoidosis in the same family. In 2 of these cases (2 black sisters) the clinical set up was similar, consisting of multivisceral sarcoidosis involving the lung and mediastinum, the skin and the peripheral lymph nodes and muscles, with poor general condition and dependence on, or resistance to corticosteroids. Although the two sisters lived in different countries for several years and despite the 4-year age difference between them, the disease began in both cases at the age of 40 years. The history of this family is exemplarily in favour of a genetic predisposition and suggests than the penetrance of genetic transmission is underevaluated. Systematic pulmonary clinical and radiological examinations performed in the relatives of patients with sarcoidosis might provide information on the true incidence of familial cases. Studies of the genetic equipment of these familial cases would perhaps constitute a line of research aimed at determining the pathogenesis of the disease. PMID- 2196660 TI - [A rare tumor of the mediastinum: benign hemangioma]. AB - Mediastinal hemangiomas are rare tumours occurring more often in children and young adults. A new case is reported in a 21 years old male who had an anterior mediastinal mass detected on a routine chest roentgenogram. Pre-operative investigations including CT, venous digital angiography, MRI did not aid in the right diagnosis. The mass was totally removed surgically although involving extensively adjacent structures. Histologic examination of the tumour showed it to be a benign venous hemangioma. Clinical, radiological, pathologic features of mediastinal hemangiomas are reviewed and discussed. PMID- 2196661 TI - [Computers against isolation]. PMID- 2196662 TI - Diagnostic and prognostic significance of beta 2-microglobulin during HIV infection. AB - The serum levels of beta 2-microglobulin (beta 2-m) were determined in 80 intravenous drug addicts (IVDA) with acquired immunodeficiency syndrome (AIDS), in 128 HIV-positive IVDA with persistent generalized lymphadenopathy (PGL) and in 44 HIV-seronegative IVDA. Seventy-two out of 80 (90%) AIDS patients had elevated serum beta 2-m levels and high levels of beta 2-m were also found in 105 of 128 (82%) HIV-infected subjects without AIDS. The mean beta 2-m level was significantly higher in HIV-infected patients with PGL than in HIV-negative IVDA. Nine out of 64 (14%) PGL patients developed AIDS in a period of 24-54 months. In these patients the mean beta 2-m level (5.16 +/- 2.37 mg/l), obtained from sera stored at the first observation, was significantly higher than in the other PGL patients (3.40 +/- 1.03 mg/l); in particular, 5 out of 7 PGL patients with beta 2 m levels greater than 5.0 mg/l showed an advanced disease. PMID- 2196663 TI - The von Willebrand factor. AB - Von Willebrand factor (vWf) is a multimeric and multivalent adhesive protein which is essential for platelet adhesion to subendothelium and for stabilization of factor VIII procoagulant activity in circulation. The quantitative measurement of vWf involves essentially two different approaches. The first is based on the interaction between vWf and Gp Ib of the platelet membrane in presence of ristocetin (ristocetin cofactor activity, RiCof) and depends not only on the amount of the factor but also on its ability to bring about this interaction, large multimers being more active. The second approach involves the immunological quantitation of vWf (vWf:Ag) by its interaction with specific polyclonal or monoclonal antibodies as measured by several methods, i.e., electroimmunoassay, immunoradiometric assay and immunoenzymatic assay. Although in the majority of type II von Willebrand disease (vWd) with dysfunctional vWf there is a discrepancy between RiCof and vWf:Ag, it should be emphasized that RiCof activity does not entirely reflect the 'true' activity of vWf since it does not explore all the functions of this factor; furthermore, the relationship between degree of multimerization and RiCof level is not always tenable, as for example in vWd 'Vicenza'. For the diagnosis of congenital and acquired vWd RiCof assay together with family investigation is the eligible test, with an estimated ability to detect at least 50% of the carriers of the abnormal gene, including mildly affected patients; vWf:Ag appears less sensitive and, on the basis of studies carried out in our laboratory, a relative sensitivity of 64% is proposed. Both assays require the definition of separate normal ranges for children and adults and for 0 and non-0 blood group subjects; a nonparametric approach in a large sample of normal subjects is advisable. With RiCof assay performed by an aggregometric method using formalin-fixed platelets an interassay variability of 6% and 8.5% respectively for high- and low-control plasma was found in our laboratory. With vWf:Ag assayed by an ELISA method a variability of 7% for low- and 6% for high-control plasma was found. Thus, both methods appear sufficiently precise for clinical use. The use of an internal pool calibrated against an international standard allows to perform comparable interlaboratory measurements. To further improve standardization of these assays, collaborative studies seem urgently required. PMID- 2196664 TI - Specific assays of hemostasis proteins: fibrinogen. AB - Fibrinogen levels are considered a useful indicator in several pathological conditions and recent epidemiological studies have indicated a relationship between fibrinogen levels and increased risk of cardiovascular disease. An accurate measurement of this protein is therefore recommended and the Italian Committee for Standardization of Methods in Hematology and Laboratory has carried out a collaborative study to determine accuracy, precision and comparability of results obtained by six different methods, i.e., 1. Blomback and Blomback method, 2. clotting assay according to von Clauss, 3. radial immunodiffusion according to Mancini et al., 4. total amount of clottable fibrinogen by means of turbidimetric assay according to Ellis and Stransky, and 5. with ChromotimeSystem, 6. prothrombin time (PT)-derived fibrinogen assay on ACL coagulometer. The most accurate resulted the von Clauss method, but only if calibrated with an internal standard; in fact, when the manufacturer's tables are used, the method proved to be highly inaccurate. The best precision, both intra- and between-laboratory, was obtained by the PT-derived test on ACL. On the basis of this still incomplete evaluation of the CISMEL study data, we can conclude that: i. some methods used in clinical laboratories give accurate results only after adequate calibration; ii. a reference standard pool may be a valid tool for calibration and for a better between-laboratory comparability; iii. a predilution of the samples with high fibrinogen levels seems indicated; iv. automation markedly increases the precision of methods. PMID- 2196665 TI - Expression of HLA class I antigens in human tumors and their involvement in tumor growth. AB - A decreased expression of major histocompatibility complex (MHC) class I antigens is a common feature of many experimental and human tumors and can often be correlated with malignancy grade. In fact, reduction of class I antigens is associated in most tumors with an enhanced ability to elude immune surveillance. Loss of HLA-A,B,C antigens ranges from a decrease in the percentage of A,B,C positive cells to selective loss of particular antigens and total loss of class I molecule expression. In man, this has been documented in melanomas, carcinomas, lymphomas, neuroblastoma and acute leukemias. The reduction in membrane antigens is generally associated with a parallel fall in immunoprecipitable intracellular proteins and the corresponding mRNAs in the absence of structural changes in the coding genes. The literature concerning the above mentioned topics is reviewed and discussed. PMID- 2196666 TI - [The place of nuclear medicine procedures in clarifying the state of gastrointestinal bleeding--radionuclide monitoring]. AB - Radionuclide studies today can specify the actual state of gastrointestinal bleeding. "Radionuclide monitoring" characterises a method that allows a long term surveillance of the patient for hours or even days (sequential scintigraphy). Labelling of the intravasal space is best met by in vivo/vitro labelling of the red blood cells with 99mTc, "Radionuclide monitoring" may positively influence current concepts of diagnosis or treatment control of patients suffering from gastrointestinal bleeding. PMID- 2196667 TI - [Comparative efficacy of sonography, computed tomography, ERCP and angiography in the diagnosis of primary carcinomas of the gallbladder]. AB - Based on a patient material of 12 patients suffering from a histologically confirmed primary carcinoma of the gallbladder the preoperative diagnoses via the four imaging methods of sonography, CT, ERCP and angiography were compared with the intraoperative findings. Surprisingly, ERCP and angiography turned out to be the most accurate of these diagnostic methods. PMID- 2196668 TI - [Comparative efficacy of sonography, computed tomography, ERCP and angiography in the diagnosis of primary papillary carcinomas]. AB - In a patient group of 19 patients suffering from a primary carcinoma of the papilla of Vater that had been confirmed by surgery and histology, the preoperative diagnoses arrived at by the four imaging methods of sonography, CT, ERCP and angiography were compared on the basis of the intraoperatively produced tumour findings, and the accuracy of the methods was assessed. It was found that ERCP is superior to all the other diagnostic methods in respect of carcinomas of the papilla of Vater, diagnosis being correct in more than half of the cases. Sonography yielded the diagnosis of a space-occupying growth in barely one-half of the cases, whereas CT reported a mass in two-thirds of the cases, but no clear organotopic diagnosis was possible. In no case did angiography supply a pointer towards the correct final diagnosis. PMID- 2196669 TI - Spinal epidural abscesses in adults: review and report of iatrogenic cases. AB - A retrospective review of the medical records of adults with diagnosed spinal epidural abscess (SEA) admitted to the Departments of Neurosurgery and Infectious Diseases at the University Hospital of Umea, Sweden, during a 10-year-period (1978-1987) is presented. 10 patients were diagnosed as having SEA during the study period. An iatrogenic origin was suspected in 5. Spondylitis was the most common source of infection. Bacteriological aetiology was confirmed in 8 cases and Staphylococcus aureus was the most common aetiological agent. Trauma and degenerative diseases of the spine, were underlying conditions in 6 cases. Laminectomy was performed in 7 cases. 5/6 patients operated within 48 h after onset of neurological symptoms improved. The remaining case with therapy resistant tuberculous spondylitis died. One patient with surgery after 96 h became paretic. 2/3 conservatively treated patients had a successful outcome while the third patient had a permanent paraparesis due to missed diagnosis. Early diagnosis and early laminectomy are still the most important prognostic factors. Recommended initial antibiotic therapy is the combination of a cephalosporin with extended spectrum and metronidazole. PMID- 2196670 TI - Norfloxacin vs. pivmecillinam in the treatment of uncomplicated lower urinary tract infections in hospitalized elderly patients. AB - In a single-blind, randomized study of multicentre trial design 343 hospitalized geriatric patients (median age 83 years) suffering from symptomatic urinary tract infections (UTI) were treated with either norfloxacin 200 mg twice daily or pivmecillinam 200 mg 3 times daily orally for 7 days to compare the clinical efficacy and safety of the antibiotics in the elderly. The pathogen was Escherichia coli in 56.7%, other gram-negative rods in 37.2% and gram-positive cocci in 6.1%. Up to 18 days after cessation of treatment the original pathogen was eradicated in 60.5% of the 114 who were assessable for the effect of norfloxacin therapy and in 36.5% of the 96 patients in the pivmecillinam group (p less than 0.001). Adverse drug reactions, mostly gastrointestinal disturbances, were noticed in single cases. PMID- 2196671 TI - Effect of cloxacillin prophylaxis on the bacterial flora of craniotomy wounds. AB - During a double-blind placebo-controlled study, the effect of cloxacillin prophylaxis in craniotomies on samples taken for culture from 334 operation wounds in 279 patients was assessed. Patients and operations were equally divided over the cloxacillin and placebo groups. In the cloxacillin group significantly fewer samples contained microorganisms than was the case in the placebo group both just after the incision was made (p less than 0.05) and just before closure of the wound (p less than 0.001). The contaminating bacteria found most frequently were Propionibacterium acnes and Staphylococcus epidermidis. For material collected immediately after the incision, the percentage of cultures positive for S. epidermidis was significantly (p = 0.001) lower in the cloxacillin group than in the placebo group; the percentage of cultures with P. acnes did not differ between the two groups. For samples taken just before the wound was closed, the percentage of cultures with P. acnes or S. epidermidis was significantly (p = 0.008 and 0.003, respectively) lower in the cloxacillin than in the placebo group. In the placebo group neurosurgical infections occurred with P. acnes and/or S. epidermidis as causative microorganisms; in almost all cases those bacteria could be cultured from the edge of the wound. In none of the patients with an infection caused by S. aureus was the bacteria found in the operation area. In 2/6 infections in the cloxacillin group the infecting microorganisms could be cultured from the operation area. These findings support a significant reduction in the infection rate after craniotomy under cloxacillin prophylaxis compared with placebo. PMID- 2196672 TI - Acute oral candidiasis during febrile episodes in immunocompromised patients with haematologic malignancies. AB - To estimate clinical, pathogenic and serological aspects of acute oral candidiasis (AOC) during febril episodes in patients with haematologic malignancies, 23 consecutive patients who developed AOC within 7 days from start of fever were compared with 23 consecutive patients who did not develop AOC. The duration of fever and severe granulocytopenia (less than 0.5 x 10(9)/l) was significantly longer in patients with AOC than in patients without AOC, the median differences between the patients with and without AOC being 4 and 3 days, respectively. Development of AOC could not be correlated to a change in the qualitative composition of the oral microflora. The thrombocyte count was lower in patients with AOC on day 4, whereas no differences were found in leukocyte counts. The prevalences of Candida albicans agglutinin titres greater than or equal to 5 were similar in patients with (24%) and without AOC (33%), and in controls (29%). Seroconversion or a significant increase in the agglutinin titre occurred in 4 patients with AOC and long-lasting fever, who became afebrile after systemic antifungal therapy. It is concluded that AOC is associated with long lasting fever and decreased bone marrow function as judged by low thrombocyte counts, but not related to specific bacteria in the oral cavity or to an increased occurrence of C. albicans antibodies in the serum. PMID- 2196673 TI - Comparing brains. AB - Some animals have larger brains than others, but it is not yet known why. Species differences in life-style, including dietary habits and patterns of development of the young, are associated with variation in brain weight, independently of the effects of body weight and evolutionary history. Taken together with behavioral and neuroanatomical analyses, these studies begin to suggest the evolutionary pressures that favor different sized brains and brain components. PMID- 2196674 TI - Systemic steroid therapy for acute gout: a clinical trial and review of the literature. AB - Nonsteroidal antiinflammatory drugs are frequently used as initial therapy in acute gout. In select cases, however, colchicine has been recommended as an alternative therapy. A review of the literature raises significant concerns regarding the cost to benefit ratio of using colchicine in this setting. A survey of alternative forms of therapies showed few studies investigating the efficacy and side effects of a short course of oral steroids, and little support for this modality in standard textbooks. Our preliminary study suggests that a short course of oral corticosteroid therapy can be used effectively for acute gout when NSAIDs are contraindicated. The use of prednisone 30 to 50 mg or its equivalent initially, and gradually tapered over 10 days, results in clinical resolution without rebound arthropathy or steroid complications in most patients. As a result, we rarely use colchicine in the management of acute gout in our practice. PMID- 2196675 TI - Risk factors of second-line antirheumatic drugs in rheumatoid arthritis. PMID- 2196676 TI - Pulmonary complications of antirheumatic drug therapy. AB - Drug-induced pulmonary disease should be considered in all patients receiving these antirheumatic agents who develop new pulmonary symptoms. When a drug reaction is suspected, the possible offending agents should be discontinued, required respiratory support instituted, and infection or other pulmonary processes excluded. Pathological evaluation by lung biopsy may be needed to define the disorder and rule out infection. Treatment with corticosteroids should be considered in patients with acute pneumonitis. While significant morbidity and even death may occur with drug-induced pulmonary disease, prompt evaluation and treatment of these disorders often results in complete resolution of the process. PMID- 2196677 TI - Purely granulomatous Wegener's granulomatosis: a new concept for an old disease. AB - In summary, PGWG corresponds to an early phase of WG, presenting only with extravascular granuloma. Primarily, ENT, eye, or lung tissues are involved, but any organ may be affected. The diagnosis is made by typical palisading granuloma associated with elevated c-ANCA levels in the patients' serum. The concept of an early granulomatous lesion (PGWG) facilitates the early diagnosis of WG and leads to classification of different forms of disease according to the multistep evolution hypothesis: first PGWG, then localized or limited forms of the disease, and ultimately generalized vasculitis with renal involvement (classical WG). The concept of PGWG forms the basis for future therapeutic trials where folate antagonists are restricted to PGWG, while immunosuppressive treatment is required for the other stages of WG. PMID- 2196678 TI - Alcohol abuse and osteoporosis. PMID- 2196679 TI - Magnetic resonance: safety considerations and future directions. PMID- 2196680 TI - Nuclear magnetic resonance in clinical medicine: an overview. PMID- 2196681 TI - The use of nuclear magnetic resonance to study muscle metabolism in very low birth weight infants. PMID- 2196683 TI - 31P nuclear magnetic resonance spectroscopy in the human neonatal brain. PMID- 2196682 TI - Neonatal seizure: magnetic resonance spectroscopic findings. PMID- 2196684 TI - In vivo multinuclear magnetic resonance spectroscopy investigations of cerebral development and metabolic encephalopathy using neonatal animal models. AB - This review has attempted to indicate areas of investigation that in vivo MRS methodology is particularly suited for and would answer important questions related to neonatal cerebral development or injury. There are several metabolites (PEth, PCr, NAA, taurine, glutamate) and lipids detectable by in vivo 31P or 1H MRS, which show substantial changes in concentration during ontogenesis. Do these biochemical markers correlate with major morphological changes, such as myelination? If they do, can this be used to quantitate abnormalities in brain development from congenital abnormalities or metabolic encephalopathies? In the neutral to mild acidic range (7.0 greater than pHi greater than 6.5) adult and neonatal brain appear to have similar intrinsic physicochemical buffering capacity. However, at the extremes of pHi induced by respiratory alkalosis or severe acidosis from partial ischemia, the possibility exists that the buffering capacities of adult and neonatal brain differ. Whether this is true requires further investigations using both neonates and adults, or perhaps more preferably, multiple measurements on a single species throughout its developmental period. Such studies are now feasible because multinuclear in vivo MRS can provide a large body of information from individual animals. A similar study design could prove useful for investigations of changes in cerebral resistance to hypoxia, ischemia, or asphyxia during development. The roles that blood pressure, glucose, temperature, or the administration of extrinsic buffers and drugs have on modulating the severity of and relationship between changes in blood flow, energy metabolites, or pHi, are all amenable to study using in vivo MRS. Furthermore, all of these variables can be measured simultaneously. The kinetics of brain acid and lactate homeostasis during chronic cerebral insults or following acute insults has not been thoroughly examined in either neonates or adult animals. There is evidence to suggest that following ischemia or seizures, brain acidosis resolves before brain lactosis. However, the clinical diagnostic significance of this post-insult uncoupling between pHi and lactate remains to be established. Finally, the application of in vivo MRS methodology to study the effects of trauma, drugs, environmental toxins, and other metabolic encephalopathies on neonatal cerebral perfusion and metabolism are virtually unexplored. Hopefully, the material presented here will prompt researchers to consider the application of in vivo MRS to new avenues of investigation. PMID- 2196685 TI - Myelodysplastic syndrome: a review from University Hospital, Kuala Lumpur. AB - Twenty patients with Myelodysplastic Syndrome (MDS) were diagnosed in University Hospital, Kuala Lumpur over a 5 year period. They were subclassified using the French American British (FAB) criteria. 90% of the patients were above 40 years old and the sex ratio was about equal. The predominant presenting symptom was anaemia and there was paucity of physical signs at presentation. Patients with 'aggressive' subtypes of MDS i.e. refractory anaemia with excess blasts (RAEB), refractory anaemia with excess blasts in transformation (RAEB(-)+) and chronic myelomonocytic leukaemia (CMML) had more frequent thrombocytopenia and neutropenia and their marrow pictures frequently had dysmegakaryopoiesis and dysgranulopoiesis as compared to more the "benign" subtypes i.e. refractory anaemia (RA) and refractory leukaemic anaemia with ringed sideroblasts (RARS). Four patients had leukaemic transformation and all of them came from the 'aggressive' subtypes. The current views on treatment of MDS are discussed. PMID- 2196686 TI - Management of diabetes mellitus in pregnancy. AB - Diabetes is a common problem in pregnancy and the incidence depends on the racial predisposition and geographical distribution where the reports originate. Despite improvement in perinatal care, many serious clinical problems are still associated with diabetes during pregnancy. The overall strategy of management includes early identification of diabetes during pregnancy, combined management to achieve optimal glucose control with dietary manipulation and insulin, maternal and fetal monitoring during the antenatal period and determination of the delivery time. Intensive intrapartum monitoring and neonatal care at delivery and thereafter are also essential. The outlook for the newborn of the diabetic mother has changed dramatically in recent years and both perinatal mortality and morbidity rate have declined as a result of pre-pregnancy preparation and meticulous control of maternal blood glucose throughout pregnancy. Successful pregnancy outcome depends on the cooperation of the patient, the obstetrician, the physician, the neonatologist and the health educator. PMID- 2196687 TI - Fiberoptic bronchoscopy in the diagnosis of pulmonary tuberculosis. AB - We reviewed the records of 80 patients with culture-positive pulmonary tuberculosis. Forty (50%) had their diagnoses established by sputum smears and cultures alone, 20 (25%) by brush/wash specimens from fiberoptic bronchoscopy alone, 18 (22.5%) from both sources, and two (2.5%) by gastric smears. The average age of the patients was 71.3 years, and only 20% had symptoms typical of pulmonary tuberculosis. Our data reveal that findings in smears from fiberoptic bronchoscopy were of comparable sensitivity (80%) to those of sputum (72.5%); in 25/80 (31.25%), diagnosis was made exclusively by fiberoptic bronchoscopy. Such a high sensitivity of fiberoptic bronchoscopy in the diagnosis of pulmonary tuberculosis indicates a threefold rise (P = .018) in the number of diagnoses made in this manner compared to our figures from 1983 (10% of diagnoses made by fiberoptic bronchoscopy). Forty-three of the 80 patients (53.8%) had either a negative sputum smear or no sputum available. Thirty of the 43 patients (69.8%) had diagnostic bronchoscopy, which provided an immediate diagnosis (smear positivity) in 18 patients (60%). Transbronchial biopsy was most useful in excluding associated malignancy. Fiberoptic bronchoscopy is playing an increasingly significant role in the diagnosis of pulmonary tuberculosis. Further studies are essential to evaluate cost effectiveness, specificity of fiberoptic bronchoscopy, and the influence of the procedure on morbidity and mortality in pulmonary tuberculosis. PMID- 2196689 TI - Gastritis: a common source of acute bleeding in the upper gastrointestinal tract? AB - Gastritis is commonly reported as a frequent cause of acute hemorrhage of the upper gastrointestinal tract. Our experience and a review of the literature suggest that gastritis, a relatively common endoscopic finding, is rarely the source of acute upper gastrointestinal bleeding. PMID- 2196688 TI - Obstetric ultrasonography in a tertiary military medical referral center. AB - Antenatal ultrasonography is an integral component of diagnostic tests available to the practicing obstetrician. Periodic assessment of sonographic services offered and their diagnostic reliability is necessary for good patient care and quality assurance/risk management (QA/RM) documentation. We report the findings from a 1-year review of antenatal ultrasonographic services provided in a military referral center serving the Department of Defense in the southeastern United States. During the study period, 1627 obstetric scans were done by our Department of Radiology. Most of the examinations (139 [85%]) were done on patients served on a continuing basis by USAF Medical Center, Keesler; 236 (15%) studies were done on patients referred by other military hospitals throughout the region. Of all scans available for review, 1529 were normal, whereas 98 (6%) revealed clinically significant abnormalities. We address herein the results of this periodic assessment, as well as implications for referral among Department of Defense hospitals. PMID- 2196691 TI - Plasma cell leukemia and hyperviscosity syndrome. AB - A 56-year-old man had dyspnea, weight loss, hemoptysis, and a generalized bleeding diathesis. Physical examination disclosed hepatosplenomegaly, congestive heart failure, and multiple sites of bleeding. Severe anemia, thrombocytopenia, rouleaux formation, and a leukocytosis with circulating immature plasma cells were observed, along with azotemia, hyperuricemia, and marked elevation of total proteins with a monoclonal IgG kappa spike. The finding of increased serum viscosity confirmed the clinical impression of the hyperviscosity syndrome. Emergency plasma exchange produced marked improvement in the clinical manifestations of hyperviscosity syndrome. Systemic chemotherapy resulted in a partial remission of the disease, but the patient ultimately died of complications of treatment. In this review, we discuss the diagnosis and management of the hyperviscosity syndrome. PMID- 2196690 TI - Sigmoid volvulus in childhood. AB - Although it is common in the adult population, sigmoid volvulus is unusual in childhood. We report the cases of four children treated for sigmoid volvulus, and we review an additional 44 cases. The mean age of occurrence was 8 years. Predisposing factors were present in 33%. Abdominal pain (66%), vomiting (31%), and obstipation (10%) were the most common symptoms. Abdominal findings included distention (69%), tenderness (41%), and a mass (10%). The classic roentgenographic omega sign of volvulus was present on plain films in only 29% of the cases. Barium enema examination was diagnostic in 61% of the cases in which it was used. Nonoperative treatment by barium enema or proctoscopy was successful in all 17 cases in which it was attempted. The recurrence rate after nonoperative treatment was 31%. Thirty children had operation. The mortality in the group of patients having "derotation" alone was 29%. Immediate resection was associated with a 25% mortality; none of the patients who had elective resection died. Sigmoid resection is the definitive treatment for children as well as adults, but nonoperative decompression to allow for elective resection should be attempted in patients who have no evidence of peritonitis. PMID- 2196692 TI - Stenosing flexor tenosynovitis. AB - A review of 253 consecutive digits with stenosing flexor tenosynovitis was done to clarify the respective role of steroid injection and surgical release in the management of stenosing flexor tenosynovitis. Treatment selection was based on the patient's age and severity of presenting complaints. In patients aged 10 years or more, analysis showed no statistically significant difference between results with steroid injection and surgical release. Surgical treatment was associated with higher cost and more complications. Based on this review, we recommend up to three injections of 20 mg of triamcinolone into the digital flexor sheath as the initial management of nonlocking, stenosing flexor tenosynovitis in adults. Initial management by surgical release is reserved for children and patients with digits locked in flexion. PMID- 2196693 TI - Efficacy of bomb shelters: with lessons from the Hamburg firestorm. AB - Shelters for protection against the effects of nuclear weapons are often stated to be useless, largely because of firestorms. Recent models purport to show that nuclear weapons are more likely to cause firestorms than previously thought. These controversial models are based on uncertain assumptions, which are difficult or impossible to test. Regardless of the predictive validity of fire models, conclusions about the ability of shelters to protect their occupants against firestorms, if they occur, are based primarily on historical experience. A review of the original data from the Hamburg firestorm shows that almost all persons in adequate shelters survived, contradicting a currently prevailing belief that all died. The results of the strategic bombing during World War II and of nuclear weapons tests show that a considerable level of population protection can be achieved through attention to proper shelter design. PMID- 2196694 TI - George J. Heuer: a commemorative review. AB - George J. Heuer was the 13th resident surgeon trained by William S. Halsted. A leading proponent of the halstedian school of surgery, he went on to develop leading surgical programs at Cincinnati and Cornell. A master technician, he emphasized surgical education during a career that spanned four decades. This biographic review commemorates Dr. Heuer's contributions to the growth of surgery and restores him to his proper place as a founding father of American surgery. PMID- 2196695 TI - Chronic necrotizing pulmonary aspergillosis treated by endobronchial amphotericin B. AB - Chronic necrotizing pulmonary aspergillosis is an indolent, locally invasive form of Aspergillus infection. Treatment options are limited and controversial. Resection is often curative if the patient has sufficient ventilatory reserve. Even though intravenous amphotericin B is effective in a few patients, toxicity limits its use. Aerosolized amphotericin B has proven ineffective. Anecdotal reports of intracavitary and endobronchial antifungal therapy show limited success. Our patient had unresectable chronic necrotizing pulmonary aspergillosis treated successfully with intracavitary instillation of amphotericin B, delivered via the flexible fiberoptic bronchoscope. PMID- 2196696 TI - Disulfiram-induced hepatitis. AB - We reported a case of disulfiram-induced hepatitis with unique clinical features and compared our case with others in the literature. Our patient had headache, mild fever, nausea, vomiting, rash, and eosinophilia after 3 weeks of disulfiram therapy. Subsequent liver biopsy showed low-grade lobular hepatitis. After disulfiram therapy was discontinued, symptoms subsided and results of liver function tests returned to normal. PMID- 2196698 TI - Hangman's fracture resulting from improper seat belt use. AB - Diagonal seat belt application without accompanying lap belt closure may produce severe cervical spine injuries, including hangman's fracture and decapitation. Seat belts are effective in reducing injury, but they must be worn properly to do so. Passive restraint systems involving a diagonal seat belt may be hazardous if the motorist does not use the accompanying lap belt. We have presented a case in which the driver in a motor vehicle accident sustained a hangman's fracture (bilateral fracture of the pedicles of C-2) caused by use of a diagonal seat belt without accompanying lap belt closure. The mechanism of injury, as classically described in judicial hanging, is hyperextension and distraction, which occurred when the victim "submarined" under the diagonal seat belt and was caught at the neck. PMID- 2196697 TI - Systemic Torulopsis glabrata infection in a neonate. AB - We have reported a case of neonatal Torulopsis glabrata peritonitis and ventriculitis associated with a ventriculoperitoneal shunt. Treatment of fungemia and ventriculitis with amphotericin B and 5-fluorocytosine was successful. PMID- 2196699 TI - [Pages from the life of S.I. Kantorovich, a prominent public health administrator of Ukraine]. PMID- 2196700 TI - Comparison of an enzyme-immunoassay with a radio-immunoassay method for the detection of the hepatitis markers anti-HBs, anti-HBc and HBsAg. AB - A comparative study was carried out on a radio-immunoassay (RIA) and enzyme immunoassay (EIA) method for detecting the hepatitis markers anti-HBs, anti-HBc and HBsAg. The results indicated that the RIA and EIA were comparable for the HBsAg marker but that the RIA test was more sensitive for anti-HBs and more specific for anti-HBc. The conclusion was that if the EIA test is used for these markers, the laboratory and clinician must be aware of these limitations. PMID- 2196701 TI - Actuarial status of the SMI Trust Fund. PMID- 2196702 TI - Actuarial status of the HI Trust Fund. PMID- 2196704 TI - Heterogeneity and natural history of hereditary breast cancer. Surgical implications. AB - The properly compiled cancer family history can prove to be one of the most cost effective and powerful instruments for cancer control in breast cancer. Needed, however, is an understanding of the heterogeneity of hereditary breast cancer and knowledge of those facets of its natural history that can expedite a syndrome diagnosis. Priority concerns for cancer control in hereditary breast cancer are the development of registries of cancer-prone families, willingness by third party carriers to help defray the costs of surveillance, and more research in molecular genetics. PMID- 2196703 TI - Epidemiology and natural history of breast cancer. Implications for the body weight-breast cancer controversy. AB - The mechanisms of differentiation of the mammary gland apparently can explain the contradictory findings on the association of breast cancer with excess body weight. Excess weight may be related to the initiation of breast cancer in premenopausal women through its effect on menstrual cycles and on progesterone secretion and to the promotion of breast cancer in postmenopausal women through its effect on estrogen metabolism. Although body weight is unlikely to be as strong a risk factor for breast cancer as it is for endometrial cancer, it may have a greater importance from a public health point of view, because the ratio of the incidence of breast cancer to that of endometrial cancer is 4.5 in whites and 6 in blacks. Thus, more studies seem warranted. It is not possible, however, to rule out the view that the reported correlation between excess weight and breast cancer is attributable to failure to adjust for potential confounders, such as dietary fat. New insights may come from the combined assessment of weight, different types of dietary fat, and reproductive history factors known to be involved in the natural history of breast cancer. For example, in the Women's Intervention Nutrition Study (WINS), the survival rate of breast cancer patients on a 20 per cent fat diet is being compared with that of breast cancer patients of similar weight keeping their usual 35 to 40 per cent fat diet. This investigation will show whether dietary fat influences the rate of progression (metastasis) and of promotion (occurrence of cancer in the other breast) independent of body weight. PMID- 2196706 TI - Techniques and results of aspiration cytology for diagnosis of benign and malignant diseases of the breast. AB - The use of fine needle aspiration to obtain cellular material for pathologic examination was introduced in 1930 but fell out of favor for several years. In today's medical environment, fine needle aspiration is proving to be more efficacious and cost effective than conventional breast biopsy. The authors detail the technique, its complications, the reliability of the results and ways to improve it, and the suitability of the material for hormone receptor assays, detection of tumor-related problems, and ultrastructural study as well as for standard cytologic diagnosis. PMID- 2196705 TI - Mammography and breast cancer screening. AB - Breast radiography should be performed only with film-screen mammography or xeromammography. At least two views of each breast should be obtained, and for film-screen mammography, at least one of these should be the oblique view. Quality assurance is becoming a significant concern in breast cancer screening. The ACR Mammography Accreditation Program takes into account the qualifications of the personnel, the performance of the x-ray equipment, and a peer review of the final product: the diagnostic image. The mammographic signs of malignancy can be divided into primary, secondary, and indirect. The accuracy of mammography depends on several factors, but the greatest limitation is the density of the breast tissue. Very dense tissue makes detection of breast cancer difficult, and a negative mammogram should never deter one from a biopsy of a clinically suspect mass. New consensus guidelines for breast cancer screening were developed to bring uniformity to the recommendations of the American Cancer Society, the National Cancer Institute, and various professional medical societies. These new guidelines reflect the encouraging results from recent clinical trials, as well as some discouraging reports on breast self-examination and the baseline mammogram. The underutilization of screening mammography is a problem of significant concern to both private and public health agencies. Barriers to mammographic screening include lack of awareness of the benefits of screening, physicians' misconceptions about patient compliance, concerns about radiation risk and overdiagnosis, fear of mastectomy, a perception that a mammogram involves great discomfort, and relatively high cost. Nationwide educational programs are under way to counter misconceptions about mammography, and various strategies are evolving to overcome the other barriers. Sonography is a useful adjunct to mammography for cyst-solid differentiation, but mammography is the only imaging modality effective for the early detection of breast cancer. PMID- 2196707 TI - Factors influencing cosmetic outcome of conservative surgery and radiotherapy for breast cancer. AB - Increasing acceptance of conservative therapy for early breast cancer has made the cosmetic outcome of the treated breast an important endpoint for evaluation. A number of interrelated patient, tumor, and treatment factors will determine the ultimate cosmetic outcome. Attention to surgical and radiotherapeutic technique should lead to good to excellent overall cosmetic results in the majority of patients. PMID- 2196708 TI - On occlusal forces in dentitions with implant-supported fixed cantilever prostheses. AB - The main aims of this thesis were (1) to study the functional characteristics of dentitions with mandibular implant-supported fixed cantilever prostheses - IFCP s occluding with complete dentures, (2) to study in detail the magnitudes and distributions of axially directed closing and chewing forces in such dentitions, (3) to study the influence of number and distribution of occlusal contacts on the magnitude and distribution of closing and chewing forces, (4) to assess the vertical bending moment and the resulting vertical bending stress in the cantilever joints and (5) to find out whether the force distribution over the cantilever beams and the resulting vertical bending stress in the cantilever joint are influenced by the type of prosthetic construction in the opposing jaw. Closing and chewing forces were registered in altogether seventeen subjects by means of miniature strain gauge transducers mounted bilaterally and symmetrically in performed matrices in prosthetic appliances. Four, six or eight transducers, evenly distributed over the tooth-arch, permitted registrations of axially directed occlusal forces in several occluding areas simultaneously. In Papers I IV, the implant-supported prostheses were installed in the mandible and occluded with complete dentures. In Paper V, group A, the fixture-supported prostheses were installed in the maxilla and occluded with tooth-supported fixed partial dentures whereas in group B, the arrangements were analogous to those in Papers I IV. All subjects exhibited a rhythmic chewing pattern and preferred one side for chewing although both sides were used. Most chewing sequences were terminated with swallowing with occlusal force development. The mean total forces acting over the tooth-arch varied somewhat between groups and occlusal arrangements but averaged 350 and 170 N for closing and chewing respectively. Closing and chewing forces increased distally along the cantilever beams when occluding with complete dentures and decreased distally when occluding with fixed partial dentures. The distally increasing force distribution pattern could be altered to a distally decreasing force distribution pattern by infraoccluding the second cantilever unit by as little as 100 microns. Calculated vertical bending moments and stresses in the cantilever joints of the preferred chewing sides created by closing and chewing forces were larger in dentitions where the IFCP occluded with a complete denture than in dentitions where the IFCP occluded with a tooth supported fixed partial denture. PMID- 2196709 TI - [Florence Nightingale's ideas highly current in 1990]. PMID- 2196710 TI - [Worthwhile to know about insulin injections]. PMID- 2196711 TI - [Nurses' House]. PMID- 2196712 TI - [Nurses and the right to vote]. PMID- 2196713 TI - [Militant Miss Norrie]. PMID- 2196714 TI - [Exocrine pancreatic insufficiency in dogs]. AB - Pancreatic exocrine insufficiency is the most common cause of maldigestion in dogs. This is usually caused by irreversible atrophy of the pancreas which subsequently requires life-long substitution therapy. The pathophysiology, symptoms and diagnosis are briefly reviewed in the present paper. The Trypsin like-immunoreactivity test is recommended for establishing the diagnosis. Finally, treatment and possible causes of the failure of therapy are discussed. PMID- 2196715 TI - [The effect of tobacco smoke on the activity of proteolytic enzymes and their inhibitors in human oral fluid]. AB - In vitro experiments have shown that unfractionated tobacco smoke in the known concentrations inactivates salivary proteolysis inhibitors, not influencing proteolytic enzymes activities. This phenomenon may be one of the pathogenetic factors contributing to the development of local inflammatory reaction of the oral mucosa in tobacco smokers. PMID- 2196716 TI - [Regulation of the blood-brain barrier permeability in suppurative-inflammatory diseases of the maxillofacial area]. AB - Hematoencephalic barrier (HEB) permeability was studied in 78 rabbits. HEB permeability for 32P was examined in animals with phlegmons on the posterior paws and on the maxillofacial area; HEB permeability was sharply increased in the latter group animals. Central cholinolytics and antioxidants were used to normalize this parameter in the rabbits with maxillofacial phlegmons. PMID- 2196717 TI - [A comparative study of breast feeding and artificial infant feeding by ultrasonic scanning]. AB - Sucking process was examined in 22 breast- and formula-fed infants by ultrasonic scanning. Analysis of the obtained echographic images of the oral cavity along the middle sagittal line has led the authors to a conclusion that employment of traditional milk soothers with both large and small holes is harmful for articulation and forms an erroneous pattern of sucking and swallowing function, this possibly resulting in abnormal development of the jaws and oral cavity organs. PMID- 2196718 TI - [A method for preparing complete removable dentures with a light-weight base]. PMID- 2196719 TI - [Lock fasteners for denture fixation]. PMID- 2196720 TI - [I. V. Buial'skii and his contribution to the development of dentistry (on the 200th anniversary of his birth)]. PMID- 2196721 TI - Evolution of the P450 gene superfamily: animal-plant 'warfare', molecular drive and human genetic differences in drug oxidation. AB - Drug-metabolizing enzymes, such as those encoded by the cytochrome P450 genes, are noted for their high degree of interspecies and intraspecies variability. We believe that much of this diversity is the result of continuous molecularly driven coevolution of plants producing phytoalexins and animals responding with new enzymes to detoxify these chemicals. One consequence of human P450 gene evolution is polymorphism in drug metabolism, leading to marked differences in the response of individuals to the toxic and carcinogenic effects of drugs and other environmental chemicals. PMID- 2196722 TI - Nitrate reductase: a target for molecular and cellular studies in higher plants. AB - Nitrate reductase (NR) is a key enzyme in the assimilation of nitrate by plants. NR expression can be selected either for or against, both at the cellular level and at the level of the whole plant, and numerous mutants affected at the locus for the nia structural gene--which encodes the NR apoenzyme--have been identified. The nia gene, which has now been cloned, is a useful tool for molecular genetic studies in higher plants; furthermore, a combined genetic and biochemical approach to studying NR should allow an insight into the catalytic process of a multicenter redox enzyme. PMID- 2196723 TI - Transcriptional repression in eukaryotes. AB - Gene transcription can be controlled by positive or negative regulatory mechanisms; a combination of both is frequently responsible for the observed expression patterns. Analysis of a number of eukaryotic systems suggests that repressors can interfere with many and perhaps all the steps required for transcriptional activation. Transcriptional repression mechanisms can usefully be divided into three major classes: inhibition of DNA binding, blocking of activation and silencing. PMID- 2196725 TI - The treatment of superficial tuberculous lymphadenitis. AB - Tuberculosis of the superficial lymph nodes responds well to chemotherapy, with uneventful resolution of the condition in 70% of patients. Nodes can appear afresh or enlarge during treatment but usually resolve. Fluctuation, discharge, sinus formation and scar breakdown occur in the minority. At the end of chemotherapy 10% may be left with residual nodes. After chemotherapy nodes can enlarge or appear afresh, usually transiently. Such events do not imply relapse, nor does the persistence of nodes presage relapse. Initial excision does not seem to affect outcome and surgical procedures should be reserved for the relief of discomfort caused by enlarged nodes or tense, fluctuant nodes. Nine months of rifampicin and isoniazid, supplemented by ethambutol for the first 2 months, is the current treatment of choice for tuberculous lymphadenitis. Shorter regimens are under investigation. PMID- 2196724 TI - Tick-borne diseases of cattle in Paraguay. II. Immunisation against anaplasmosis and babesiosis. AB - A total of 102 susceptible adult Holstein Friesian cattle imported into an area of Paraguay where anaplasmosis and babesiosis are endemic were immunised by infection with Anaplasma centrale and attenuated forms of Babesia bigemina and Babesia bovis obtained from Uruguay. The results indicated that the attenuated forms of both Babesia species protected cattle against heterologous field challenge whereas A. centrale did not invariably confer sufficient protection against a field challenge of A. marginale. PMID- 2196726 TI - The use of paraffin wax metabolism in the speciation of Mycobacterium avium intracellulare. AB - Paraffin-wax utilisation or baiting of Mycobacterium avium-intracellulare (MAI) complex organisms and other 'atypical mycobacteria' and the inability of Mycobacterium tuberculosis to utilise paraffin are known and useful if forgotten facts. Strains of possible AIDS-related MAI have been introduced into Czapek broth devoid of any carbon source other than paraffin-wax coated slides. Replicate slides showing 'in situ' growth were subjected to the following battery of tests: acid alcohol fast staining and microscopic examination of 'in situ' growth, tellurite reduction in 3 days, absence of urea hydrolysis, inability to reduce nitrates and inability to hydrolyse Tween 80. The system has been utilised to isolate and identify MAI organisms in blood from AIDS patients. The simplicity, low cost, and reduced risk of contamination make the system especially suitable for small rural laboratories and field stations as well as laboratories in developing countries. PMID- 2196727 TI - BCG vaccination and cancer. PMID- 2196728 TI - Adjuvant chemotherapy for sarcomas and carcinomas. AB - The use of adjuvant chemotherapy appears to offer many advantages to the patient with cancer. However, objective information is difficult to compile. Clinical trials all too often have only a small number of patients. In order to best demonstrate the usefulness of adjuvant chemotherapy, many of the cases discussed here had bulky disease. Based on the known principles of chemotherapy, animals with minimal residual disease following surgery would most likely benefit from adjuvant chemotherapy. By using the principles discussed at the beginning of this article and information from clinical trials, veterinarians will better be able to inform clients of possible benefits and risks in treating their pets with chemotherapy. PMID- 2196729 TI - Management of complications of cancer chemotherapy. AB - Although the use of anticancer agents can be associated with severe side effects, on a practical basis complications of therapy are minimal to nonexistent. The clinician usually learns to feel more comfortable with these drugs as he or she treats more patients, to the point where treating a cancer patient with chemotherapy will become routine practice. PMID- 2196730 TI - Biologic response modifiers: the future of cancer therapy? AB - The major shift today has been away from nonspecific compounds acting on immune mechanisms to using biologics which have specific, defined roles in acting on the immune response. The field of biologic response modification is progressing very rapidly. New peptides are being identified, as are receptors for these peptides, autocrines, lymphokines, cytokines, growth factors, differentiation factors, hormones, and so on-all of which will control body function, cell populations, and cell to cell interactions. This rapidly advancing area of research in cancer biology and cancer therapy may hold the key to the future of successful therapy. PMID- 2196731 TI - Clinical indications and applications of radiotherapy and hyperthermia in veterinary oncology. AB - The response of dogs and cats with neoplasia to radiation therapy has improved significantly during the past 10 years. This has largely been due to more aggressive radiation therapy treatment schedules, more accurate planning, and refinement of clinical indications. Sufficient numbers of dogs and cats irradiated with curative intent have not been accumulated to yet define the full impact of more aggressive therapy. However, many tumors will likely remain resistant to irradiation because of concomitant normal tissue injury that must be minimized. Systematic investigation of combination therapy (surgery, radiation, chemotherapy, and hyperthermia) should succeed in reducing local tissue side effects and increased local tumor control. A comprehensive approach to tumor management begins with decisions thoughtful of optimal treatment for suspected malignant tumors even at the time of initial examination and client counseling. An incisional biopsy provides essential information to determine the therapeutic course and should be considered prior to initial excision. More aggressive treatment, of even small tumors, early in the clinical course will lead to prolonged tumor control. Radiation therapy should be considered fundamental in the comprehensive treatment plan of many solid tumors. PMID- 2196732 TI - The treatment of multicentric canine lymphoma. AB - Canine LSA is a fatal disease if untreated, but fortunately it is also a disease that is very responsive to therapeutic intervention. It is likely that most cases seen and treated by practitioners will be managed with the currently effective drugs and with new protocols as they are developed. Other approaches, including immunotherapy and BMT, are likely to remain more in the arena of the academic institution but should be available in the referral setting for appropriate cases. Great strides have been made in the less than 30 years that canine LSA has been widely treated; it is reasonable that similar progress is to be expected in the years to come. PMID- 2196733 TI - Aggressive surgery in the management of oral neoplasia. AB - Aggressive surgical techniques such as mandibulectomy and maxillectomy have become the standard surgical treatment for oral neoplasia. The development of these procedures has provided some hope for a cure or at least extended life span in animals with oral tumors. Although large segments of bone and soft tissue are usually removed, function and cosmesis are acceptable. Postoperative complications are common but are usually treatable. Best prognosis for long-term survival is for patients with benign tumors or early SCC. Less favorable results have been found with fibrosarcoma and MM. Continued research in adjunctive treatment of these tumors may further improve the results of combined surgical and medical management. PMID- 2196734 TI - Management of canine appendicular osteosarcoma. AB - Canine appendicular osteosarcoma is a highly malignant primary bone cancer that closely resembles the same disease in humans. Although amputation alone usually controls local disease, metastatic cancer is common and is the cause of death or euthanasia in 90% of dogs by 1 year. Cisplatin (+/- doxorubicin) chemotherapy appears to improve survival time in dogs; however, metastatic cancer remains a problem. Pulmonary metastasectomy may prolong survival in carefully selected dogs. Limb-sparing, although involved and potentially fraught with complications, can result in local disease control and a functional, pain-free limb in selected dogs without adversely affecting their survival. Studies are ongoing to improve local disease control with limb-sparing and improve disease-free survival in dogs with appendicular osteosarcoma. In conclusion, dogs with osteosarcoma were previously thought to have a hopeless prognosis, but the outlook is beginning to appear more optimistic. Limb-sparing in dogs is still evolving; however, it is possible in selected cases to optimize survival and preserve limb function. PMID- 2196735 TI - Clinical approach to tumors of the skin and subcutaneous tissues. AB - With skin tumors, "a lump is only a lump" until a definitive diagnosis has been made. It is nearly impossible to make an accurate diagnosis solely on clinical signs. In some instances, fine-needle aspirate may be diagnostic; however, in all instances biopsy is the preferred method for definitively diagnosing canine and feline skin tumors. Prognosis and treatment depend on the diagnosis. PMID- 2196736 TI - The owner of the pet with cancer. AB - Cancer is an emotionally charged disease. During treatment, it is not uncommon for pet owners to engage veterinarians in frank discussions and emotional confrontations based on their fears and anxieties about cancer. Pet loss counseling skills are invaluable when dealing with clients after the death of their companion animal. Incorporating pet loss counseling into a veterinary practice is pragmatic as well as compassionate because clients who feel that they have received good emotional care in addition to medical care return to the veterinarian with new pets and recommend the practice to others. PMID- 2196737 TI - Laboratory abnormalities in patients with cancer. AB - In this problem-oriented review of abnormalities associated with cancer, we have emphasized distinctive diagnostic points related to pathogenesis for each condition and outlined how the approach to management is determined by pathogenesis. For abnormalities of the complete blood count, it is important to distinguish between abnormalities directly related to marrow malignancy and abnormalities associated with extramarrow malignancy. Hemopoietic tumors consist of developmentally deficient blood cells produced by a clonal population of malignant stem cells. Tumors infiltrating marrow cause overcrowding in the limited marrow microenviroment. Extramarrow malignancies cause blood abnormalities, but the potential for normal marrow function is present. Abnormalities of blood cells secondary to therapy are usually clearly identified by consideration of clinical history. The initial differential diagnosis for hypercalcemia is malignancy. An aggressive diagnostic approach may be needed to identify the neoplasm, and therapy should incorporate measures to prevent renal failure. Hypoproteinemia and hyperproteinemia may be caused by neoplasia. Monoclonal gammopathies should be identified and may be associated with hyperviscosity syndrome. Hypoglycemia in the adult animal is most frequently caused by insulin-secreting tumors, but it has also been associated with hepatic and other tumors. Increased blood urea nitrogen, creatinine, lipase, amylase, and liver enzyme activities may also be caused by malignancy. Inadequate urine concentrating ability may be caused by hypercalcemia or malignancy-associated renal insufficiency. Hematuria in older animals is suggestive of urinary tract neoplasia. Exfoliated tumor cells may be identified in the urine sediment of these patients. PMID- 2196738 TI - The cytologic diagnosis of neoplasia. AB - With minimal skill, most veterinarians can use cytology to differentiate inflammation from neoplasia and thus provide useful information for the direction of further diagnostic testing. The experienced cytologist can definitively diagnose several specific neoplasms and make a tentative diagnosis of neoplasia for many other types of tumors. This information is useful in establishing a prognosis and in directing appropriate therapy. Cytologic findings should be correlated with other clinical and laboratory information. When the cytologic diagnosis of neoplasia is uncertain, the presence of tumor and tumor cell type should be confirmed histopathologically. PMID- 2196739 TI - Clinical management of the cancer patient. Taking a biopsy. AB - Good biopsy protocol depends on excellent interaction with diagnostic pathologists. This article reviews the essentials of diagnostic appraisal, specimen preparation, biopsy interpretation, proper reporting, and implementation of biopsy results in case management. The emphasis is on biopsy of malignancy. PMID- 2196740 TI - Clinical management of the cancer patient. Principles and applications of chemotherapy. AB - Chemotherapy is an important and effective modality of modern cancer treatment. Practitioners are encouraged to become familiar with this branch of medicine because it can be employed in the local practice setting. In the process of providing service for clientele and care for their pets, practicing clinicians will inevitably be confronted with involvement in some aspect of a chemotherapeutic protocol initiated by a veterinary oncologist. With an understanding of the principles of chemotherapy, the toxicities inherent in the use of these compounds, and the judicious handling of these agents, veterinarians will be able to provide a better standard of care for the animals presented to them. PMID- 2196741 TI - Capsomer proteins of bacteriophage PRD1, a bacterial virus with a membrane. AB - Bacteriophage PRD1 infecting Escherichia coli and Salmonella typhimurium translocates its membrane from the host plasma membrane to the virus particle. One obligatory component in this process is the major capsid protein. In this investigation we describe characteristics of the homomultimeric major and minor capsid proteins including the sequences of the corresponding genes. The minor capsid protein was found to contain a short collagen-like region (Gly-X-Y)6. This is the first time this motif has been reported for a prokaryotic protein. PMID- 2196742 TI - Identification and nucleotide sequence of the gene encoding a surface antigen induced by vaccinia virus. AB - The gene encoding the specific antigen (S antigen) induced on the surface of vaccinia virus-infected cells was mapped on the viral genome by the construction of recombinant viruses. The S gene is located in the 1.5-kbp XbaI-AccII fragment between 11.1 and 12.6 kbp from the right end of the viral genome. Nucleotide sequencing of the fragment revealed an open reading frame (ORF) of 351 codons capable of producing a polypeptide with a molecular weight (MW) of 40,701 Da. Mapping of the S mRNA by primer extension indicates the presence of the transcription initiation site that precedes the translation initiation codon by 14 nucleotides. The region preceding the S mRNA start site is extremely A/T-rich and has sequence similarity with other early genes. The signal for termination of transcription of the early genes, TTTTTAT, is included near the end of the ORF. The deduced amino acid sequence contains a typical membrane signal characterized by a hydrophobic region in the N-terminus. An early polypeptide with a MW of 40 kDa, in agreement with the size predicted from the ORF, was synthesized by cell free translation of the mRNA selected by hybridization to a plasmid containing the region of the ORF. PMID- 2196743 TI - Characterization of preearly genes in the terminal repetition of bacteriophage BF23 DNA by nucleotide sequencing and restriction mapping. AB - A finer restriction map of the terminal repetition of bacteriophage BF23 DNA was determined and used to localize a 3.4-kbp deletion in the terminal repetition and to determine the physical location of preearly gene A2-A3. The nucleotide sequence of gene A2-A3 was determined and shown to code for a protein of 125 amino acids with no indication of a membrane transport sequence. The beginning of an adjacent gene, probably gene A1, was also sequenced. PMID- 2196744 TI - Identity of genes A2 and A3 of bacteriophage BF23. AB - The polypeptide coded by gene A3 of bacteriophage BF23 has been purified and its N-terminal amino acid sequence determined. This sequence is identical to the N terminal sequence of the polypeptide coded by gene A2. The two gene products have identical molecular weight. We conclude that these two gene products are identical, and are coded by one and the same gene, namely gene A2-A3, which was previously thought to be two genes, A2 and A3. PMID- 2196745 TI - Restricted expression of measles virus in primary rat astroglial cells. AB - Persistent infection of the central nervous system (CNS) with measles virus (MV) is associated with characteristic restrictions of viral envelope gene expression as documented in subacute sclerosing panencephalitis (SSPE), measles inclusion body encephalitis (MIBE), or subacute measles encephalitis (SAME) in rats. To determine whether these restrictions are the result of a long lasting virus-host cell interaction or primarily based on intrinsic brain cell factors MV gene expression was analyzed in primary rat astroglial cultures. It could be shown that MV infection of these cells led to a defective replication cycle with a reduced synthesis of viral envelope proteins and a steep expression gradient of the monocistronic viral mRNAs similar to the findings in brain tissue of SSPE, MIBE, and SAME. This restriction of MV gene expression has not been observed in cells of nonneural origin. We suggest that this cell-type specific regulation of MV gene expression contributes to early events in the establishment of MV persistent infection in CNS tissue. PMID- 2196746 TI - [Long-term arterial blockade and retrograde venous perfusion in peripheral arterial occlusive diseases]. AB - The method of longterm artificial arterial blockade in patients with peripheral arterial occlusive disease (PAOD) opens new therapeutic possibilities. However, it is yet not clear if and how the suspected dilation of collateral arteries can be therapeutically used. The retrograde venous perfusion permits the transport of active substances in high concentrations into ischemic areas. The resulting temporary local damping or even blockade of sympathetic innervation can under certain conditions achieve therapeutic effects. A longterm arterial blockade can be performed even in case of trophic lesions. This permits treatment in stage IV of PAOD. It has been proved that antibiotics reach a lesion by retrograde venous perfusion faster and better than by systemic application, especially in badly compensated cases. However, sufficient experience on the therapeutic effect and possible side effects in stage IV is still lacking. PMID- 2196748 TI - Application of an alternative approach for using the SOS chromotest to screen complex indeterminate mixtures. AB - We report on the application of an alternative approach to screen two complex indeterminate mixtures for genotoxic activity with the SOS chromotest, a simple quantitative colorimetric short-term bacterial genotoxicity assay. Considering the mixtures as a complex matrix, we evaluated the shape of the dose response curve of the direct acting reference genotoxin 4-nitroquinoline-1-oxide (4-NQO) with and without the matrix and found for one mixture a previously unrecognized genotoxic potential. PMID- 2196747 TI - Discrepancies between total and nutritional skin microcirculation in patients with peripheral arterial occlusive disease (PAOD). AB - Clinical observations indicate that a discrepancy may exist between the total and nutritional skin microcirculation in extremities of patients with peripheral arterial occlusive disease (PAOD), which suggests a local maldistribution of blood flow. The present study was performed to investigate how the skin blood flow is locally distributed in the toes of patients with PAOD. The total skin microcirculation was evaluated by laser Doppler fluxmetry (LDF), and the blood flow in the nutritional skin capillaries by dynamic capillaroscopy. This combination was simultaneously used to study the nailfold microcirculation in the big toe of 12 legs of 8 patients with various degrees of PAOD, using 10 legs of 8 healthy subjects as control. Capillary blood cell velocity (CBV) was evaluated by a new computerized videophotometric technique (CapiFlow). It was found that the nutritional blood flow, as evaluated by CBV, was similar in both groups (0.2 vs. 0.25 mm/s, NS), whereas the total blood flow, as evaluated by LDF, was significantly (p less than 0.05) increased in toes of patients with PAOD (11.7 AU) in comparison to normal subjects (2.0 AU). The postocclusive reactive hyperemia was impaired for both CBV (6% vs. 70%, p less than 0.05) and LDF (14% vs. 50%, p less than 0.01) in the PAOD group. The prevalence of flow motion (30% vs. 80%) was significantly (p less than 0.05) lower in patients as compared to controls. It is concluded that the resting blood flow in the skin microcirculation is increased but maldistributed in patients with PAOD. The reactivity of the microcirculation is also impaired in the affected region.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196749 TI - [Recent findings in fetal lung development: structure, surfactant, lung fluid]. AB - A great deal of lung development takes place after birth; new alveoli continue to develop until 8-11 years. However, the differentiation of epithelial cells is characteristic of the fetal lung from 24 weeks of gestation onwards: this is the point at which the surfactant containing type II cells can first be identified. Lung blood flow and the metabolic rate of type II cells increase in parallel rates the last 20% of the gestation period. The timely synthesis of surfactant depends on the availability of the fetal hormones T3, cortisol and prolactin, whereas this synthesis is inhibited by insulin and testosterone. Endogenous surfactant consists of 80% phosphatidylcholine and 10% protein. A sufficient quantity of surfactant is only available at term. Nowadayx, surfactant deficiency can be treated successfully with various exogenous surfactant preparations. Fetal lung liquid contributes about one half to the amniotic fluid. It is partly secreted by an active transport system. Secretion is inhibited by the stimulation of beta-adrenergic receptors in the lung tissue. The epithelial surface of the alveoli is a barrier which limits protein penetration considerably; lung liquid contains minimal amounts of protein. Under pathological conditions (RDS, haemorrhagic lung oedema) the alveolar barrier is disturbed so that plasma protein penetrate into the air spaces and form hyaline membranes. PMID- 2196750 TI - [Qualitative analysis with Doppler spectra of the umbilical artery and fetal aorta in normal pregnancies]. AB - Blood flow velocity waveforms were recorded between the 20th and 40th week of gestation from the umbilical and fetal aorta (n = 230 each) in 130 uncomplicated pregnancies. The S/D ratio, the Resistance Index (RI) and the Pulsatility Index (PI) were calculated. In the umbilical artery the indices showed a significant decrease in the observation interval. In the fetal aorta we could not register any significant change of these indices. All values are presented as reference curves. The importance of the Doppler assessment of the circulation in these vessels for the management of high-risk pregnancy is emphasized. PMID- 2196751 TI - [A case of septic ovarian vein thrombosis]. AB - Puerperal ovarian vein thrombosis commonly originates from purulent necrotic endomyometritis. The incidence is published to be 1 to 600 deliveries. According to the puerperal uterine drainage, the predominant location is the right ovarian vein in 90% of all cases. The leading symptoms are lower abdominal pain, fever and leucocytosis. Discrepancy between the given clinical picture and the insignificant findings on gynaecologic examinations is common. PMID- 2196752 TI - [Case report of a clinically silent perforation of a Medusa intrauterine device into the abdominal cavity with simultaneous intact mens II pregnancy]. AB - In this article is reported on an unnoticed perforation of IUD (Medusa) in the abdomen during an intact pregnancy in the second month. The practice of diagnosis and treatment is described. PMID- 2196753 TI - Muscle diseases relevant to the anesthetist. PMID- 2196754 TI - Anesthesia in neuromuscular diseases. AB - Neuromuscular diseases raise a lot of anesthesia related problems. The first is the hitherto unknown disease discovered by an unexpected adverse reaction to anesthetics or/and muscle relaxants up to a life-threatening incident. A second problem is the probable, suspected or proven disposition to malignant hyperthermia in patients with other neuromuscular diseases. Furthermore, severe rhabdomyolysis can be induced in myopathic muscle by the application of succinylcholine alone or in combination with inhalational anesthetics resulting in hyperkalemia, myoglobinuria and CK-elevation, sometimes followed by cardiac arrest. Cardiomyopathy is a common feature in many neuromuscular diseases. All cardiodepressant agents must be avoided. Specific problems with muscle relaxants arise in myasthenia gravis and in the myotonias. In the later stages of severe neuromuscular diseases the main problem concerning anesthesia is respiratory failure. The individual risk of every patient has to be evaluated before anesthesia. Recommendations for the anesthetic management are given. PMID- 2196755 TI - Malignant hyperthermia. Treatment of the acute episode. PMID- 2196756 TI - In vivo bone-mineral measurement. How and why--a review. PMID- 2196757 TI - DNA cytometry of musculoskeletal tumors. A review. AB - In conclusion, all the benign soft tissue tumors analyzed so far have been been diploid, whereas the malignant entities include both diploid or aneuploid variants. Further, there is a relationship between ploidy level and histologic malignancy grade. The main value of DNA analysis seems to be that it provides objective support for histologic diagnosis as to benignity and malignancy grade. Occasionally, a discrepancy between ploidy and grade is encountered. Apart from the fact that aneuploidy precludes benignity, it may prove that ploidy level in malignancy is a better predictor of clinical course than histologic grade. However, this can only be established by analyzing each malignant entity separately, because the validity of DNA cytometry probably varies with histogenetic tumor type. PMID- 2196758 TI - In vivo and in vitro effects of cytokines on the generation of NK cell-mediated antitumor activity. PMID- 2196759 TI - Multicenter study of hospital adverse drug reactions. PMID- 2196760 TI - Sensitivity to endothelin-1 in mesenteric beds and aortic rings of 4-week-old spontaneously hypertensive rats. PMID- 2196761 TI - Histamine in the retina: recent progress and perspectives. AB - This article presents some new findings, and shortly surveys recently published data, on histamine (HA) in the retina of several vertebrates (carp, hen, rabbit, rat, guinea pig, cow, man). Analysis of various parameters (HA level, activity of histidine decarboxylase and HA-methyltransferase, release and uptake of HA, 3H mepyramine binding, effect of HA on cAMP accumulation, diurnal variations) in vertebrate retina and brain shows that histaminergic systems in these sites are comparable, although some species-dependent differences have been observed. Interestingly, exposure of dark-adapted rabbits to light affects several histaminergic parameters selectively, i.e. in the retina and not in the brain. The reviewed data suggest that in retinas of at least some vertebrates HA may be a physiologically important amine. PMID- 2196763 TI - Plasma histamine levels in polytraumatized patients. AB - In a prospective clinical trial, plasma histamine levels were measured in 28 polytrauma patients on day 1, 5 and 14 after trauma. Only those subjects who died were drop-outs. All patients had severe polytrauma with at least 3 body regions involved. The median plasma histamine levels at all three time points were significantly higher than in patients with single trauma of the extremities or before selective orthopaedic surgery but still in the normal range (less than 1 ng/ml). However, all patients with plasma levels above 1 ng/ml on days 1 and 5 died, as did all patients with levels above 0.5 ng/ml on day 1. Thus the elevation of plasma histamine levels, for whatever reason, appears to be a prognostic factor for bad outcome in polytrauma patients. PMID- 2196764 TI - An immunoenzymoassay for histamine. AB - The clinical diagnosis of allergies needs appropriate tools for the measurement of histamine release from leukocyte suspension of affected patients. In the last few years the established fluorometric procedure has been challenged by alternatives like histamine radioimmunoassays (RIA). Although measurements of histamine with the latter methods make this procedure more accessible as a diagnostic tool, further simplifications are always welcomed. A newly developed immunoenzymoassay for histamine is described in the present work and compared to a recent radioimmunoassay. Sensitivity and specificity are shown to be comparable in both procedures. PMID- 2196762 TI - Staub and Bovet Award 1989 lecture. Some aspects of mast cell subtypes from human lung tissue. PMID- 2196765 TI - Our approach to primary enuresis in children. AB - In 150 children with enuresis following protocol was applied: a detailed questionnaire, a voiding chart, clinical examination, ultrasound of the kidneys, and uroflow. A tentative treatment based on the flowchart shown in the paper is installed. If after 4-5 weeks no amelioration is observed observation is completed by a urodynamical examination and a permictional urethocystography and the treatment adapted to the results. On this bases each enuresis case could be categorized in one of 4 groups with typical clinical and urodynamical characteristics requiring a specific treatment. The study shows that by an appropriate selective treatment including physical and psychological training and medication nearly all children can get dry. PMID- 2196766 TI - [Prenatal diagnosis and neonatal management of posterior urethral valves: apropos of 33 case reports]. AB - The existence of valves in the posterior urethra (33 cases) carries a poor prognosis since 25 to 50% of these newborns will develop terminal renal insufficiency. Antenatal diagnosis permits early treatment and should lead to an improved functional prognosis in cases where the number of nephrons is not too low. PMID- 2196767 TI - Prenatal diagnosis and postpartal therapy of fetal obstructions related to the urinary tract. AB - 114 fetal malformations were diagnosed by ultrasound in the years 1983-1987 at our institute. 32 of these malformations involved the urinary tract. Fetuses with multicystic dysplasic kidneys and oligohydramnios have only a poor prognosis. In obstructive uropathy, however, exact antenatal diagnosis makes early leads to specific postpartal urological therapy. Modern ultrasound equipment makes it possible to localize the site of obstruction and/or dilatation in fetuses. The amount of amnion fluid indicates the degree of obstruction and is an important factor the postpartal prognosis of the children. Relieve of obstruction should be the first step of urological therapy directly after birth. We prefer to perform reconstructive surgery as soon as possible in the first 2 to 3 weeks of life. In children with subpelvic stenosis pyeloplasty is performed in the first weeks of life. Our results of 13 pyeloplasties in newborn are favourable. In children with megaureters dynamic scintigraphy or pressure flow studies (Whitaker test) are performed to diagnose or to exclude obstruction as a cause of dilatation (n = 14). In case of obstruction we perform an ureterocutaneostomy (Ring- or Sober procedure) immediately. Urethral valves causing subvesical obstruction could be treated by transvesical antegrade valve ablation, performed in 9 newborn with good success. PMID- 2196768 TI - [Ureterocele: diagnosis and treatment at birth]. AB - Antenatal ultrasound diagnosis of ureterocele remains difficult. Two cases are presented. The presumption of the diagnosis was realized at 25 weeks of amenorrhea in one case; in the other case, the diagnosis was sure at 38 weeks. A vesical exploration was performed after visualization of a dilatation of the upper pole of the kidney associated with an ureteral distension. An ectopic ureterocele was display in one case and an orthotopic ureterocele in the other case. These findings were confirmed during the radiologic examination after the birth. An hemi-nephroureterectomy was realized for an ectopic ureterocele in the first case, and an enucleation for an orthotopic bilateral ureterocele in the second case. doses of 1 and 100 micrograms+100 g BW, T3 was without effect of inhibited 45Ca uptake. In ventricles and atria, the stimulatory effect of T3 on 45Ca uptake was very rapid [within 2 min, at which time it was at or near maximum (50-90% above control] and then declined gradually and was not seen after 10-20 min. Of the several calcium blockers employees, verapamil (organic) and cadmium (inorganic) were found to be the most effective. Verapamil and cadmium produced a rapid, transient, and dose-related inhibition of 45Ca uptake in the tissues examined (except fat tissue where, under the experimental conditions employed, 45Ca uptake was undetected). Verapamil, given iv (200 micrograms/100 g BW) or ip (1 mg+100 g BW), reduced tissue 45Ca uptake by 50-90% within 2 or 10 min, respectively, and then its inhibitory effect diminished rapidly and was not seen after 20-30 min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196769 TI - [Urodynamic, radiological and clinical studies in children with spina bifida]. AB - In 61 children with myelomeningocele urodynamic, radiological and clinical data are correlated. Bladder hyperactivity (low compliance and instability) was present in 77% of the cases. No correlation was observed with the clinical neurological level. However impairment of renal function by hydronephrosis or reflux occurred in 19 of the 33 cases presenting a bladder hyperpressure of more than 40 cm of water for bladder filling volumes lower than the bladder capacity accepted as normal for the children's age. Two thirds of urinary infections occurred in the children with hyperactive bladders. Detrusor-sphincter dyssynergia is observed in only 29% of cases. PMID- 2196770 TI - [2 classical contraindications for enteroplasty in spina bifida]. AB - The authors report two cases of spina bifida which illustrate the two major contraindications of enteroplasty and stress the importance of a detubulated intestinal patch and an isometric ureterocystometry in the diagnosis and treatment of neurogenic bladder. PMID- 2196771 TI - Effects of propranolol in non-Q-wave acute myocardial infarction in the beta blocker heart attack trial. AB - Although the beneficial effects of long-term therapy with beta-adrenergic blocking agents in patients recovering from acute myocardial infarction (AMI) are established, the effect of this therapy on the cardiac event rate in patients recovering from a non-Q-wave AMI is unknown. This post hoc analysis of the Beta Blocker Heart Attack Trial (BHAT) evaluates the effects of daily administration of propranolol 180 or 240 mg/day after non-Q-wave AMI. The study population consisted of 601 patients with enzymatically proven non-Q-wave AMI, which represented 17% of the BHAT patients. Of these, 310 patients were randomized to receive propranolol and 291 patients to placebo. There were no significant baseline differences between groups. The median follow-up was 24.6 months. Mortality was 7.8% (sudden death 4.8%) in the propranolol group and 7.9% (sudden death 4.8%) in the placebo group (p greater than 0.99, log rank test). Reinfarction rate was 7.4% in the propranolol group and 6.5% in the placebo group (p greater than 0.63, log rank test). The need for coronary bypass surgery was similar in the 2 groups. However, more patients randomized to placebo developed angina. In this post hoc group analysis of the BHAT, propranolol was not shown to be beneficial in reducing the cardiac event rate in patients recovering from a non-Q-wave AMI. PMID- 2196772 TI - Myocardial protection by intravenous diltiazem during angioplasty of single vessel coronary artery disease. AB - The possible cardioprotective effect of diltiazem during ischemia caused by percutaneous transluminal coronary angioplasty was tested. Electrocardiograms and myocardial lactate, hypoxanthine and urate production were determined in 26 patients with a stenosis in the left anterior descending artery without angiographically demonstrable collaterals. Measurements took place before angioplasty, after each of 4 occlusions and 15 minutes after the last balloon inflation. Patients were randomly given placebo or DL-diltiazem (0.4 mg/kg as a bolus intravenously, followed by an infusion of 15 mg/hr). During angioplasty the ST-segment elevation for the anterior wall leads V2, V4 and V6, and the intracoronary lead was similar for both groups, as was lactate release. Diltiazem significantly reduced cardiac hypoxanthine release immediately after angioplasty from 63 to 88% (p less than 0.05). The drug diminished urate production after the last dilatation by 82% (p less than 0.05). In conclusion, intravenous infusion of diltiazem reduced cardiac adenosine triphosphate breakdown during angioplasty as shown by diminished hypoxanthine and urate production. In contrast, diltiazem was unable to attenuate ST-segment elevation and lactate release. PMID- 2196773 TI - Quantitative exercise thallium-201 rotational tomography for evaluation of patients with prior myocardial infarction. AB - The utility of stress-redistribution thallium-201 myocardial perfusion single photon emission computed tomography (SPECT) in patients with a prior single myocardial infarction was studied in 66 patients who were tested by both SPECT and coronary angiography. SPECT was quantified by comparing the patients' circumferential count profiles to a previously established normal data base and by plotting the results onto a polar coordinate map that localized defects to the 3 major coronary artery territories. The pattern of reversibility of the quantitatively detected defects was assessed by consensus visual analysis. SPECT thallium-201 detected myocardial infarction in 62 of 66 patients (sensitivity = 94%). Sixty-five percent of the infarct zones showed some reversibility at 4-hour imaging which corresponded with angiographic evidence of flow to the infarct zones in 95.5% of cases. Late (18 to 24 hours) imaging, done in 26 patients, showed complete or partial reversibility of 29% of infarct zone segments which were nonreversible on 4-hour images. To improve specificity for detection of disease in coronary arteries supplying the non-infarct territories, new quantitative criteria were developed that took into consideration contiguity of defects with the infarct zone. Accuracy for detection of patients with multivessel coronary disease by quantitative thallium-201 SPECT was 86%, which was significantly higher than those of the clinical response to exercise (48%), the exercise electrocardiographic response (56%) or their combination (65%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196774 TI - Antianginal, hemodynamic and coronary vascular effects of captopril in stable angina pectoris. AB - A pilot study was performed to assess the short-term effects of intravenous captopril on anginal threshold and systemic and coronary hemodynamics in patients with stable angina pectoris. Twelve patients with documented coronary artery disease, stable angina pectoris and normal left ventricular function were studied by an incremental atrial pacing stress test before and after intravenous captopril (n = 8) or placebo (n = 4). There were no significant differences in the extent of coronary disease or left ventricular function between the 2 groups and resting plasma-renin levels were normal. Captopril increased the time to angina (14 +/- 4 to 9 +/- 5 minutes, p less than 0.05), increased heart rate at development of angina (126 +/- 7 to 142 +/- 7 beats/min, p less than 0.05) and tended to increase coronary blood flow (229 +/- 154 to 296 +/- 259 ml/min, p = 0.11) and decrease coronary vascular resistance (53 +/- 10 to 47 +/- 3 dynes s cm 5/1,000, p = 0.11) at peak stress without alteration in systemic hemodynamics. No significant changes were seen after placebo administration. Therefore, intravenous captopril appears to cause a short-term increase of coronary vascular reserve, and anginal threshold in patients with chronic stable angina. This effect appears to be independent of inhibition of the systemic renin-angiotensin system or systemic hemodynamic changes. PMID- 2196775 TI - Effect of Type A behavior on exercise test outcome in coronary artery disease. AB - The outcome of the diagnostic exercise test depends on such patient-related factors as age, maximum exercise heart rate, exercise time and severity of the underlying coronary artery disease (CAD). This study examined the hypothesis that type A behavior would affect the amount of effort expended, as indicated by the exercise time and the maximum heart rate achieved, thereby resulting in differences in exercise test outcome. A total of 1,260 patients with suspected CAD, all of whom had coronary angiography, a structured interview to assess type A behavior and a treadmill exercise test, participated. Of these patients, 818 (65%) had significant CAD, and 852 (68%) were type A. There were no differences between type A and B patients in either maximum heart rate or total exercise time. Among both type A and B subjects, 36% of treadmill tests were positive. Exercise test sensitivity was similar for both groups (69% for type A vs 72% for type B, p = 0.39). Similarly, specificity was similar for both groups (87% for type A vs 80% for type B, p = 0.09). Results did not change after using logistic regression to control for potential confounding factors. Thus, type A behavior does not need to be taken into account when interpreting exercise test outcome. PMID- 2196776 TI - Development of the embryonic chick wing bud from stage 24 to stage 32. AB - If a graft is placed in an early chick wing bud, the location of the graft after several days of further development cannot be predicted solely from the rate of proximal-distal outgrowth. The movement of the graft depends on the rate of outgrowth of the wing but also on morphogenetic tissue movements intrinsic to the wing and on accommodation to the growth and morphogenetic movements of the body of the embryo. Numerous experiments have been reported in which tissue grafted into ectopic sites in the wing causes abnormal wing development. These experiments have been discussed in terms of pattern formation or positional information. However, until the movement of wing tissue during normal development is understood, it cannot be known in what way the development of grafts placed in ectopic sites is abnormal. Previous experiments have demonstrated that carbon particles placed in the wing move in the same manner as grafts of wing mesenchyme, but the carbon particles do not affect normal wing development. Carbon particles were placed in the wing, dorsal to the base of the wing, and cranial and caudal to the wing, to plot the expected movement of a graft and to discover how this movement can be predicted from the tissue movements at the base of the wing. It is concluded that three tissue movements are responsible for the movement of a graft. These are outgrowth at a rate determined by the rate of cell division, formation of the shoulder through caudal movement of the tissues cranial to the wing, and ventral movement of prospective flank ventral to somite 19. These three tissue movements and their influence on normal wing development are discussed. PMID- 2196777 TI - Dendritic reticulum cells and immunophenotype in aspiration biopsies of lymph nodes. Value in the subclassification of non-Hodgkin's lymphomas. AB - Twenty-seven lymph node aspirates were identified for which histologic confirmation of non-Hodgkin's lymphoma was subsequently obtained. Fifteen aspirates interpreted as reactive hyperplasia were also examined. All aspirates were studied by immunoperoxidase on cytospin preparations with the use of antibodies DRC1, kappa, lambda, CD3, CD5, and CD20. The follicular lymphomas could not be identified reliably by morphologic examination of aspirate smears. Clusters of DRC1-positive (DRC1+) cells were present in seven of seven follicular lymphomas, one of one mantle zone lymphoma, and one of seven small lymphocytic lymphomas. Rare DRC1+ cells were present in one of one diffuse mixed and one of seven large cell lymphomas. One lymphoblastic, one Burkitt's, and two diffuse small cleaved cell lymphomas had no DRC1+ cells. None of the seven follicular lymphomas was CD5 positive (CD5+), whereas five of the seven small lymphocytic lymphomas were CD5+. Conversely, all seven follicular lymphomas were CD20 positive (CD20+), but only one of seven small lymphocytic lymphomas was CD20+. Nineteen of the lymphomas, including all 7 of the follicular lymphomas, were either kappa or lambda positive. The other eight lymphomas were T-cell (1), B cell (1), true histiocytic (1), or "null" cell (5). The reactive aspirates had both kappa- and lambda-positive B-cells. Seven of the 15 had clusters of DRC1+ cells. To further evaluate these antibodies, the authors studied 29 additional, surgically biopsied, non-Hodgkin's lymphomas that had not been aspirated. Similar results were obtained, except that three of five diffuse small cleaved cell lymphomas had DRC1+ cells. DRC1, in conjunction with antibodies to CD5, CD20, kappa, and lambda, helps to distinguish follicular lymphoma from small lymphocytic lymphoma. DRC1 is not useful in separating reactive hyperplasia from follicular lymphoma. PMID- 2196778 TI - Human proliferative sparganosis. A new Japanese case. AB - Human proliferative sparganosis is a rare parasitic disease in which the larval cestodes of unknown species proliferate in the various organs in the whole body. The authors describe a patient with innumerable parasites in the buttock and pelvic bone. The parasites were of globular or egg-like forms, up to 3 mm in diameter. Histologically, the wavy tegument, a few layers of epidermal cells, underdeveloped muscle cells, excretory channels, and calcareous corpuscles were found in the parasites. These morphologic findings confirmed the nature of maldifferentiated plerocercoid. The serologic data suggested a close relation between Sparganum proliferum and Spirometra erinacei. PMID- 2196779 TI - Philip Levine award lecture. Chromosome translocations and oncogenes in human lymphoid tumors. AB - Chromosome studies are helping to identify oncogenes, both known and previously unknown, involved in the pathogenesis of human lymphocytic tumors; and mechanisms by which the function of these genes is critically altered. Most extensively studied have been the chromosome translocations involving the myc gene in Burkitt's lymphomas and the bcl-2 gene in low-grade lymphomas, where "activation" of the oncogene results from association with a transcriptionally active immunoglobulin gene. Other putative oncogenes, similarly involved in translocations with immunoglobulin genes (in B-cell tumors) or T-cell receptor genes (in T-cell tumors), are currently being investigated, as well as alternative mechanisms of myc gene activation in these neoplasms. Limited clinical applications of these studies have already been forthcoming, and they should eventually lead to improvements in diagnosis, prognosis, and even therapy. PMID- 2196780 TI - Oncogene amplification and expression. Importance of methodologic considerations. PMID- 2196781 TI - Meckel's diverticulum. PMID- 2196782 TI - Gastrointestinal motility disorders in diabetes mellitus. AB - Gastrointestinal motor abnormalities are common in patients with diabetes mellitus and may result in significant morbidity. Patients may present with a wide range of symptoms, including manifestations of organ involvement or poor glucose control. Derangements of motility may result in complicated and difficult management problems. This paper reviews the clinical features, pathophysiology, and treatment of diabetic gastrointestinal motility disorders. PMID- 2196783 TI - A new mechanical lithotripter for the treatment of large common bile duct stones. AB - A prospective uncontrolled multi-center trial of a prototype mechanical lithotripter was performed in 30 patients with common bile duct calculi. Standard endoscopic sphincterotomy had failed to remove all stones, primarily because of large size (26 patients). Stone size ranged from 13 to 35 mm. Forty-three of 45 stones (97%) were successfully captured, fragmented, and extracted with this newly designed mechanical lithotripter. The overall success rate of 93% using this simple and inexpensive modality compares favorably with other methods under investigation for the treatment of common bile duct stones not amenable to routine endoscopic measures. PMID- 2196784 TI - A prospective, multi-center clinical trial of the Taylor intragastric balloon for the treatment of morbid obesity. AB - This report describes the result of a prospective, multicenter clinical trial of the Taylor intragastric balloon for the treatment of morbid obesity. Sixty patients, who had failed sustained weight loss on prior dietary restriction and behavior modification programs, were enrolled in four clinical centers. The Taylor intragastric balloon, a 550-ml, pear-shaped, liquid-filled, silicone device, was inserted in all patients for a period of 16 wk, and patients were maintained on a dietary restriction and behavior modification program. During the study period, patients experienced a 11.6% decrease in mean weight and an 11.4% decrease in body mass index. Seven balloons deflated spontaneously. Examination of these balloons revealed a manufacturing defect that was subsequently corrected. No further deflations occurred. Effects of the balloons on gastric mucosa were minimal with no gastric erosions or ulcerations noted. PMID- 2196785 TI - Deciduosis of the appendix. AB - A clinicopathologic and immunohistochemical study of six cases of deciduosis of the appendix is presented. The patients were pregnant women aged 18-40 years. In four cases, the patients presented with signs and symptoms of acute appendicitis during their 26th to 31st week of pregnancy; in the other two, the lesions were discovered incidentally in appendectomy specimens obtained during cesarean section and tubal ligation at term. Histologically, the lesions were characterized by the presence of multiple, irregularly distributed submesothelial deposits of decidualized cells in the serosa of the appendix, without any associated evidence of endometriosis. By immunohistochemistry, the decidualized cells strongly labelled with vimentin antibodies, consistent with their stromal origin. In two cases, coexpression of vimentin and desmin intermediate filaments was observed, suggestive of myoid differentiation. The possible relationship of the lesions with the development of symptoms of peritoneal irritation in these patients is discussed along with a review of the literature on the abdominal complications of ectopic decidua. PMID- 2196787 TI - Central nervous system infection after endoscopic injection sclerotherapy. AB - Central nervous system (CNS) infection is a rare complication of endoscopic injection sclerotherapy (EIS) for esophageal varices. We report two patients, one of whom developed a solitary brain abscess, and the other, acute meningitis, after EIS. They presented with high fever initially, and then with changes in mental status. In the case of the solitary brain abscess, the CSF revealed evidence of infection, and CT scan disclosed a brain abscess in the left temporo parieto-occipital region. This patient received EIS six times and developed the CNS complication 4 wk after the last EIS. There was no growth in either the CSF or the abscess cultures in this case. The other patient with acute meningitis, which developed on the second day after the second session of EIS, had a positive CSF culture of Klebsiella pneumoniae. Both of these patients died despite antibiotic treatment, and craniotomy with drainage in the patient with a brain abscess. PMID- 2196786 TI - Squamous cell carcinoma after endoscopic injection sclerotherapy for esophageal varices. AB - We report two cases of squamous cell carcinoma of the esophagus following endoscopic injection sclerotherapy for esophageal varices. The interval between sclerotherapy and the development of carcinoma was 24 months in case 1 and 21 months in case 2. The sclerosant was 5% sodium morrhuate in case 1 (total dose, 10 ml) and 5% ethanolamine oleate in case 2 (45.5 ml). Although no recurrent variceal bleeding occurred after sclerotherapy, we could not perform any curative surgical treatment for esophageal cancer because of the advanced stage of the cancer and the severity of the accompanying liver dysfunction. It is difficult to determine the relationship between sclerotherapy and carcinoma; however, long term surveillance is essential to avoid overlooking a neoplasm in the esophagus after endoscopic injection sclerotherapy. PMID- 2196788 TI - Tracheoesophageal-aortic fistula complicating lye ingestion. PMID- 2196789 TI - Endoscopic leukemic polyposis. AB - Gastrointestinal involvement in leukemia and lymphoma is common and may present with varying clinical manifestations (1). We report a case of gastrointestinal bleeding with endoscopic findings of diffuse leukemic polyposis and the response to radiotherapy, with a brief review of the literature. PMID- 2196790 TI - A statewide outbreak of Escherichia coli O157:H7 infections in Washington State. AB - In November 1986, a statewide outbreak of Escherichia coli O157:H7 infections in Washington State was identified after a physician in an eastern Washington community hospitalized three patients with hemorrhagic colitis which progressed to thrombotic thrombocytopenic purpura. Epidemiologic investigation identified 37 cases in this community and linked the illnesses to a local restaurant which had served ground beef that was the suspected initial vehicle of transmission. The plasmid profile and toxin production pattern (Shiga-like toxin II alone) of the outbreak strain provided a unique strain marker. E. coli O157:H7 infections caused by this strain were simultaneously seen in other parts of the state among nursing home residents and in patients with the hemolytic-uremic syndrome, and an increase in sporadic cases of hemorrhagic colitis was noted at a Seattle health maintenance organization. It is suspected that a contaminated product, probably ground beef distributed statewide, was the common source. Tracing of this meat led to farms where rectal swabs from six (1%) of 539 cattle tested yielded E. coli O157:H7, although the plasmids and toxin production patterns of these isolates differed from the human outbreak strain. Introduction of a single strain of E. coli O157:H7 has the potential to cause widespread concurrent outbreaks. Such outbreaks are likely to escape recognition until heightened screening and surveillance for E. coli O157:H7 is established. PMID- 2196791 TI - Seroepidemiology of Strongyloides infection in the Southeast Asian refugee population in Canada. AB - As part of a screening and treatment program for intestinal parasite infections offered to newly arrived Southeast Asian refugees in Canada between July 1982 and February 1983, a total of 232 sera were tested for Strongyloides infection using an enzyme-linked immunosorbent assay (immunoglobulin G). These results were compared with coprologic results and eosinophil counts. The seroprevalence was 76.6% (131 of 171) among Kampucheans, 55.6% (15 of 27) among Laotians, and 11.8% (4 of 34) among Vietnamese. A statistically significant relation (p less than 0.001) was found between Strongyloides serology and Strongyloides infection on stool examination (prevalence, 24.7%) among Kampucheans. Eosinophilia (greater than or equal to 10%) was found to be significantly associated with both infection measures. Using coprologic results as the "gold standard," the properties of the serologic test were estimated to be: sensitivity (95%), specificity (29%), positive predictive value (30%), and negative predictive value (95%). These estimates should be regarded as minimal values, as stool examination for Strongyloides infection can be an unreliable diagnostic reference. Further evaluation of the discrepancies observed between coprologic and serologic testing is required to determine the usefulness of these tests in epidemiologic studies. PMID- 2196792 TI - Increased prevalence of clinical gallbladder disease in subjects with non-insulin dependent diabetes mellitus. AB - The association between non-insulin-dependent diabetes mellitus (NIDDM) and the prevalence of gallbladder disease remains controversial. The authors investigated this association in 1,250 men and 1,656 women from the San Antonio Heart Study (1984-1988) a population-based study of diabetes and cardiovascular disease. A total of 68% of the subjects were Mexican American, a population at high risk for both gallbladder disease and NIDDM. Gallbladder disease was assessed by self report, and the prevalence of diabetes was determined using National Diabetes Data Group criteria. NIDDM was significantly associated with gallbladder disease in Mexican-American men and women and in non-Hispanic white women. After adjustment for age, body mass index, ratio of waist-to-hip circumference, and ethnicity, using multiple logistic regression, the odds of gallbladder disease in women was 1.6 times higher if NIDDM was present (odds ratio = 1.60, 95% confidence interval 1.08-2.37). Mexican-American women also had a significantly increased prevalence of gallbladder disease relative to non-Hispanic white women (odds ratio = 2.21, 95% confidence interval 1.50-3.28). In nondiabetic women, fasting insulin was significantly related to prevalence of gallbladder disease in univariate analyses, but not in multivariate analyses. The authors conclude that women with diabetes have an increased prevalence of gallbladder disease relative to nondiabetic women and that this association is not explained by the greater adiposity or unfavorable body fat distribution of the diabetic subjects. PMID- 2196793 TI - Methotrexate in sarcoidosis. PMID- 2196794 TI - Pneumococcal vaccination: work to date and future prospects. AB - In our opinion, the conclusion from all these studies is that pneumococcal polysaccharides in the form in which they have been administered are relatively poor immunogens when compared, for example, to certain proteins such as tetanus toxoid. Had pneumococcal vaccination been the success that might reasonably have been predicted, there would be no argument, this many years later, over its merits. Although polysaccharide vaccines appear to have been effective in mass vaccination programs and in epidemic situations where presumably healthy adults have been involved, it has been more difficult to document their efficacy in individuals who are most in need of them, namely those with aberrant or senescent immune systems. There seems to be no disagreement that antibody at some concentration (the precise level remains to be determined) will, in general, be associated with protection, although in any one individual, for a variety of reasons, infection with a vaccine serotype might still occur. Thus, the clear direction for the future should be not to argue further the merits of currently available vaccine preparations, but rather to work rapidly and efficiently to develop and test new and more effective polysaccharide antigens. Studies in the past 10 years have shown that the polyribosyl ribitolphosphate (PRP) of Haemophilus influenzae type b is a far more effective antigen when conjugated to diphtheria toxoid. For example, in a study in our laboratory, vaccination of healthy young adults with PRP-conjugated diphtheria toxoid yielded serum antibody levels 10- to 100-fold higher than after PRP alone. Responses may be even better if other proteins are used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196795 TI - Medical considerations in the evaluation of the obstructed renal artery. PMID- 2196797 TI - A fungi snack? PMID- 2196796 TI - Activation of cancer cell proteases and cytotoxicity by EGF and PDGF growth factors. AB - The biological effects of EGF and PDGF growth factors on A172 and hEGFr-3T3 cell lines were studied using RBC induced cytolysis and polyacrylamide-gelatin gel electrophoresis assays. The authors report that growth factor-induced cytotoxicity in these cells is mediated by proteolytic enzymes. Treatment of A172 cells with either EGF or PDGF resulted in marked increase of their cytotoxicity (Release Index = 150%). Similarly, RBC induced release index by hEGFr-3T3 cells was elevated to 420% in the presence of 3.4 pM of EGF. However, in A172 cells, PDGF did not have a significant effect on DNA and protein synthesis indicating that stimulation of proteolytic activity is independent of the growth factor signaling pathway. Growth factor induced cytotoxicity was significantly reduced by protease inhibitors in both cell lines. Using EDTA and leupeptin several proteolytic species were identified and localized to cellular membranes as evidenced by polyacrylamide-gelatin electrophoresis assay. These data suggest that growth factors regulate the activation or secretion of proteolytic enzymes in cancer cells and may mediate the invasive and metastatic behavior of these cells. PMID- 2196798 TI - The spectrum of suffering. 1974. PMID- 2196799 TI - An epidemiologic survey of cardiovascular disease in women taking oral contraceptives. AB - Earlier epidemiologic studies have indicated an increase in mortality from certain cardiovascular diseases in young women associated with the use of oral contraceptives. However, since these studies were conducted, newer oral contraceptives containing less estrogen and progestogen have been widely adopted. In addition, an increasing majority of oral contraceptive use is by women under the age of 30 years. Early results from a new case-control study suggest the possibility that the risk of myocardial infarction associated with oral contraceptive use is now lower than in the past, although the previously observed small increase in the risk of subarachnoid hemorrhage appears to be unchanged. PMID- 2196800 TI - Role of plasma lipoproteins in the pathogenesis of atherosclerotic disease, with special reference to sex hormone effects. AB - Plasma lipoproteins constitute a complex lipid transport system. Very low-density lipoproteins transport triglycerides to peripheral tissues, whereas low-density lipoproteins are the main carriers of cholesterol. Cholesterol transport in low density lipoprotein enters body cells by way of "low-density lipoprotein receptor pathway" but may also be taken up by macrophages by way of the "scavenger pathway." Excessive influx of cholesterol by way of the "scavenger pathway" may result in deposition of cholesterol in arterial walls and atheroma formation. In a yet incompletely known process of "reverse cholesterol transport," cholesterol is carried away from the tissues to the liver by high-density lipoproteins. The above-mentioned transport processes are regulated by a well-synchronized system that involves several enzymes and lipid transport proteins. Under normal conditions, the lipoprotein system is able to balance the flow of cholesterol and other lipids in both directions between the liver and peripheral tissues. This delicate balance may be disturbed by many factors, including contraceptive steroids. The metabolic steps influenced by administration of contraceptive steroids are summarized. PMID- 2196801 TI - Disorders of the hemostatic system and the risk of the development of thrombotic and cardiovascular diseases: limitations of laboratory diagnosis. AB - The relationship between hemostatic abnormalities and thrombotic and cardiovascular diseases is summarized. All known congenital and acquired abnormalities in the biochemistry of hemostasis are related to thrombotic and cardiovascular diseases in the way that would be expected on the basis of theories about the role of balances between coagulation and fibrinolysis and between activating and inhibiting factors. Notwithstanding the consistency between theory and observed abnormalities, a causal relationship between biochemical abnormality and clinical symptoms has been proved only in a limited number of situations, and it is possible that certain abnormalities only (or also) mark pathologic events. The limitations of laboratory diagnosis of hemostatic disorders in relation to hemostasis as a local process are discussed. It is proposed that more attention be paid to methods of evaluating the local aspects, for example, methods that assess reaction products in the circulation and that can provide an averaged message of the local phenomena. In addition, such methods can provide information about the dynamic balances in the hemostatic system, whereas historically more attention has been paid to the static balances in the potential of hemostatic processes. PMID- 2196802 TI - Interrelations between carbohydrates, lipids, and the hemostatic system in relation to the risk of thrombotic and cardiovascular disease. AB - Metabolic diseases, such as obesity, impaired glucose tolerance, type I and type II diabetes, hypercholesterolemia, and hypertriglyceridemia, are among the main risk factors for the development of atherothrombosis. Various abnormalities of the hemostatic system (platelet hyperaggregability, hypercoagulability, and hypofibrinolysis) have been described in all these situations. The individual effect of each of these disease on the hemostatic system is difficult to evaluate because these states are often associated in the same patient and the treatment of one can benefit the others. Therefore it may be queried if a common abnormality of these pathologic states might explain their impact on the cardiovascular system. We have been interested by hyperinsulinemia, which is observed in obesity, impaired glucose tolerance, type II diabetes, and hypertriglyceridemia, and we have shown a very strong correlation between plasma insulin, body mass index, triglyceride levels, and one of the main inhibitors of the fibrinolytic system, plasminogen activator inhibitor-1. Partial correlation analysis showed that only the correlation between insulin and plasminogen activator inhibitor-1 was independent. Therefore a high plasma insulin level could be responsible for elevated levels of plasminogen activator inhibitor-1, which by inducing an hypofibrinolysis, could play a role in the deposition of fibrin and the development of atherothrombosis. The description of some interrelations between metabolic diseases and hemostasis is satisfactory but does not exclude specific effects of these diseases on hemostasis, such as glycation of the coagulation and fibrinolytic factors in diabetes or toxic action of lipoprotein on endothelial cells in hyperlipoproteinemia. PMID- 2196803 TI - Why do we need pharmacokinetic studies? AB - Data on the fate of sex steroids in the human organism, such as absorption, distribution, total clearance, and elimination routes, are necessary to understand and predict drug action. However, except for a few exceptions, such data are sparsely available. It is necessary to apply several approaches (descriptive, mathematic, and analytic) to describe variability and dose-response correlations, all of which are important for individualized treatment, and therefore of therapeutic relevance. In addition, such data are now unavoidable requirements for the evaluation of safety, efficacy, and quality performed by the regulatory authorities. Therefore human kinetic information is an integral part of the knowledge that forms the basis for any treatment with sex steroids. PMID- 2196804 TI - Selected aspects of the pharmacokinetics and metabolism of ethinyl estrogens and their clinical implications. AB - Careful studies in an adequate sample of subjects show a very marked degree of variability in the pharmacokinetics of ethinyl estradiol--specifically, in parameters such as area under the curve, half-life, and time to peak. This variability is seen in differences between different populations, as well as from one individual to another. These studies also show variability in area under the curve and other parameters in the same person from time to time. Such differences may equal or exceed the differences between low dose (35 micrograms) and high dose (50 micrograms) formulations. The levels of plasma ethinyl estradiol produced by a 50 micrograms dose of mestranol are similar to those from 35 micrograms of ethinyl estradiol. Thus a high-dose pill may be no higher than a low-dose pill if the nature of the estrogen is not kept in mind. Qualitative differences in the oxidative metabolites of estrogens may be of significance with respect to oncogenic potential. PMID- 2196805 TI - Clinical aspects of the relationship between oral contraceptives, abnormalities in carbohydrate metabolism, and the development of cardiovascular disease. AB - Although large epidemiologic studies indicated no difference in the frequency of diabetes mellitus in nonusers and everusers of high-dose combination oral contraceptives, other studies had shown an increased risk of impaired glucose tolerance in current users, which is estimated to be roughly twice as frequent as that in nonusers. Women at risk of developing impaired glucose tolerance while receiving high-dose oral contraceptives either had previous gestational diabetes mellitus or were older, obese, or had a positive family history of diabetes mellitus. The tendency to decreased glucose tolerance seems essentially related to the dosage and chemical structure of the progestogen used in oral contraceptives, namely, estrane and particularly gonane progestins. However, increased frequency of impaired glucose tolerance and potentially diabetes mellitus are obviously not linked to the use of the more potent gonane progestins. The use of low-dose oral contraceptives, particularly with reduced progestogen content (such as in the triphasic formulations and last-generation monophasic preparations), is accompanied by a low risk of impaired glucose tolerance, even in previous gestational diabetes mellitus. The mechanism of decreased glucose tolerance in oral contraceptive users is unknown but seems related partially to increased peripheral resistance that is potentially caused by a postreceptor defect in insulin action. Changes in insulin production or metabolic clearance rate are not excluded by recent, sophisticated investigations of carbohydrate metabolism in oral contraceptive users. Impaired glucose tolerance and diabetes mellitus, chronic hyperglycemia, and hyperinsulinemia are believed to increase atherogenic risk either by their direct action or their effects on lipid metabolism. Newer epidemiologic studies now indicate that the incidence of cardiovascular disease in low-dose, low-risk, current oral contraceptive users has been substantially decreased. The use of low-dose oral contraceptives with reduced dosages of better adapted progestogens seems effective in decreasing alterations in carbohydrate metabolism and may thereby contribute to decrease further atherogenic risk in oral contraceptive users. PMID- 2196806 TI - Mechanism of action of oral contraceptives on carbohydrate metabolism at the cellular level. AB - Although the available scientific data on the undesired metabolic effects of sex steroids have accumulated rapidly, most are of a descriptive nature, and only a few studies elucidate the impact at the cellular level and the possible interrelationship between different metabolic systems. This review summarizes the influence of different contraceptive steroid combinations on glucose metabolism and points to the possible mechanisms behind a disturbance of the euglycemic homeostasis with a concomitant change in lipid metabolism. Today the general concept is that the influence of combined sex steroid products on glucose metabolism is mainly caused by the progestogen components, although artificial estrogens may act synergistically. The diabetogenic effects of the progestogens make it important to consider the development during the last decade of the new more selective progestogens of the gonane type. From recent studies it seems, however, that intake of contraceptive combinations of ethinyl estradiol in combination with these types of gonanes, such as desogestrel and gestodene, may also be accompanied by increased insulin resistance, specifically, a hyperinsulinemic response to a glucose challenge despite unchanged glucose values compared with a baseline test. This is similar to observations made with combinations of ethinyl estradiol and other more traditional types of progestogens of the gonane and estrane type. It is conceivable that the diabetogenic effects of the progestogens are caused by a change in insulin receptor binding or a postreceptor defect in the cellular insulin action. The clinical implications of the diabetogenic effects of the sex steroids are hard to interpret, but more long-term exposure of arterial tissue to elevated concentrations of glucose and insulin results in inhibition of lipolysis and synthesis of cholesterol and triglycerides, which result in the development of lipid-filled lesions--fatty streaks--similar to those of early atherosclerosis. PMID- 2196807 TI - Low-dose oral contraceptives and carbohydrate metabolism. AB - Combined oral contraceptive use has been associated with increased incidence of impaired and diabetic glucose tolerance. Although increased risk of overt symptoms of diabetes has not been associated with oral contraceptive use, increased risk of coronary heart disease has been consistently demonstrated. Diabetes is associated with increased risk of coronary heart disease, especially in women. Elevated plasma glucose and insulin concentrations are also associated with increased risk of coronary heart disease. Studies of the effects of low-dose oral contraceptives on glucose tolerance test plasma glucose and insulin levels are reviewed. Low-dose combined oral contraceptives induced changes in measures of carbohydrate metabolism in directions consistent with increased risk of coronary heart disease. The magnitude of these changes may depend on the dose and type of progestogen. The clinical implications of these changes are unknown, but it would seem advisable to minimize them where possible. PMID- 2196808 TI - Some aspects of the relationship between oral contraceptives, lipid abnormalities, and cardiovascular disease. AB - Most epidemiologic studies suggest an association between current use of combined oral contraceptives and certain manifestations of cardiovascular disease. Most of the data relate to older preparations little used today. Decreased levels of high density lipoprotein cholesterol and increased amounts of low-density lipoprotein cholesterol were common findings with the older formulations. More recent experimental and epidemiologic data suggest that the potential risk of cardiovascular disease in oral contraceptive users is hardly predicated on an arteriosclerosis basis but related more to thromboembolic events. Because changes in the serum lipid profile are often associated with alterations in the factors of hemostasis, it seems reasonable to suggest the use of preparations void of profound changes in lipid metabolism, especially when other means of efficacy are available inclusive of the newer low-dose oral contraceptives. When risk factors for cardiovascular disease are present, determination of total cholesterol is desirable. In subjects with elevated serum cholesterol, a serum lipid profile should be determined. A woman at risk of cardiovascular disease should be carefully monitored, and repeated lipid determinations are recommended. PMID- 2196809 TI - Effects of oral contraceptives on carbohydrate and lipid metabolisms in a healthy population: the Telecom study. AB - In a cross-sectional study that aimed to identify risk factors for diabetes, 1290 consecutive, healthy, nonpregnant women of child-bearing age were examined in a center for preventive medicine. An in-depth interview about menses, use of oral contraceptives, and menopause was performed. Plasma glucose at fasting and 2 hours after a 75 gm glucose load, glycated hemoglobin A1c, fasting plasma insulin, total plasma cholesterol, and triglycerides were measured. Compared with nonusers taking no progestogens, oral contraceptive users (n = 431; 33.4%) were younger (p less than 0.001) and leaner (p less than 0.001). After adjustment for age and body mass index, oral contraceptive users had higher 2-hour plasma glucose (p less than 0.001), higher fasting plasma insulin (p less than 0.01), and higher triglycerides levels (p less than 0.01). Fasting plasma glucose, glycated hemoglobin A1c, and total cholesterol did not significantly differ between the two groups. In relation to dosage and types of steroid components, few differences have been found between high-dose and low-dose oral contraceptives or according to the estrogen-progestogen balance of the preparations. Use of oral contraceptives appears to induce an increase of insulin resistance markers, which have recently been cited as risk factors for ischemic vascular diseases. These markers should be carefully monitored in oral contraceptive users. PMID- 2196810 TI - The clinical relevance of oral contraceptive pill-induced plasma lipid changes: facts and fiction. AB - The changes in plasma lipids induced by the use of oral contraceptive pills have been shown in several studies to remain within normal physiologic limits. These changes are then probably without any clinical relevance because there is no evidence in the huge volume of oral contraceptive and cardiovascular literature that the use of oral contraceptives promotes or retards the development of atherosclerotic disease. What may appear to be favorable changes in the lipid profile attributed to oral contraceptive use may actually be associated with unfavorable changes in other parameters, such as the balance of clotting and fibrinolytic factors. A well-balanced, low-dose oral contraceptive formulation should alter any of the cardiovascular risk indicators as little as possible in either a supposedly positive or negative direction. PMID- 2196811 TI - Clinical aspects of the relationship between oral contraceptives and abnormalities of the hemostatic system: relation to the development of cardiovascular disease. AB - Epidemiologic evidence has established that oral contraceptives increase the risk of both arterial and venous thromboembolic disease. This is dose related in the case of the estrogen component for both arterial and venous events and in the case of progestogens for arterial events. It is probable that the increased rate of thromboembolic events caused by estrogen is related to hypercoagulability. Plasma levels of several clotting factors have been shown to be elevated in oral contraceptive users, and this increase is graduated according to the dose of estrogen. In pregnancy, factor VIIc is increased after cold activation of plasma at 4 degrees C overnight. Likewise, in users of oral contraceptives, both factors VIIc and XIIc are increased, which suggests a direct effect of factor XIIc on the extrinsic system. In men, the risk of ischemic heart disease is strongly and independently related to factor VIIc and fibrinogen levels; thus it is possible that in women taking oral contraceptives, the mechanism of risk is similarly mediated. There is a good case for factor VIIc as the index of flux in the coagulation system and hence of a hypercoagulable state, and indeed it may directly contribute to the generation of thrombin. This article examines the available evidence on clotting factor activity in the risk of cardiovascular disease in oral contraceptive users. PMID- 2196812 TI - Effects of newer oral contraceptives on the inhibition of coagulation and fibrinolysis in relation to dosage and type of steroid. AB - Oral contraceptives influence plasma proteins, causing changes in plasma procoagulants and fibrinolytic effectors. Estrogen is thought to be responsible for these changes, whereas progestogens, in particular those with an androgenic effect, may influence the magnitude of the changes. This concept is consistent with epidemiologic studies, suggesting a correlation between estrogen dose and cardiovascular episodes in oral contraceptive users. A delayed resolution of fibrin might contribute to an increased risk caused by decreased coagulation inhibition or fibrinolytic efficacy. Estrogen (30 micrograms or more) has a dose dependent effect on clotting factors, including antithrombin III and proteins C and S. The effect of high- and low-dose oral contraceptives containing various progestogens on the fibrinolytic system is less clear. We have found that low dose oral contraceptives containing levonorgestrel or lynestrenol enhance fibrinolysis, as revealed by an increase in plasminogen (30% to 40%), a decrease in histidine-rich glycoprotein (15% to 26%), an increase in tissue plasminogen activator activity (greater than 150%), and a decrease in tissue plasminogen activator inhibition (30% to 40%), concomitant with a slight decrease in tissue plasminogen activator antigen level (15% to 20%). New oral contraceptives contain less androgenic progestogens. Preliminary results of an ongoing study of women receiving either 20 micrograms of ethinyl estradiol with 150 micrograms of desogestrel or 30 micrograms of ethinyl estradiol plus 75 micrograms of gestodene revealed no change or changes similar to the older low-dose preparations after 6 months of treatment. Of particular importance was the finding that coagulation activation, expressed by the levels of thrombin-antithrombin III-complexes, fibrin formation, and the efficacy of fibrinolysis, expressed by the levels of fibrin degradation products, was identical in the two groups. PMID- 2196813 TI - Oral contraceptives in risk groups: exclusion or monitoring? AB - Careful consideration of absolute and relative contraindications, including newly appreciated factors such as past pregnancy-related hypertension, is essential to select what is termed the "safer women." A family history of either arterial or venous thrombosis indicates preliminary blood analysis to exclude atherogenic lipid states and thrombophilias. The goal then is to prescribe "safer pills." One should also allow for biologic variation in pharmacokinetics and end-organ responses. This can be done to a limited extent in clinical practice by using bleeding from the uterus as a "threshold bioassay." Namely, by identifying for each woman the lowest dose of a chosen estrogen-progestogen combination that is just sufficient to prevent breakthrough bleeding. Thereafter, monitoring requires attention to the development of new risk factors, regular blood pressure checks, and specific attention to the important side effects of headaches and migraines, especially if there are focal (cerebral ischemic) symptoms. PMID- 2196814 TI - Detection of Philadelphia chromosome-positive cells from glass slide smears using the polymerase chain reaction. AB - Southern and Northern blot hybridization studies and the polymerase chain reaction (PCR) have been used to analyze the bcr-abl gene complex in chronic myelogenous leukemia (CML). Because fresh or cryopreserved cells may not always be available for molecular analyses, we investigated the possibility of using routinely prepared glass slide smears of blood or bone marrow as our source of cellular material. Cellular RNA was prepared directly from the blood or bone marrow smears using a modified RNA extraction procedure. cDNA was synthesized from RNA and amplified with PCR using bcr and abl-specific primers. Using this procedure, the bcr-abl fusion gene was detected by PCR in 21 of 21 patients with CML. Three patients who had undergone allogenic bone marrow transplantation (BMT) for CML were also studied by PCR. bcr-abl was identified transiently in one patient, persisted in one patient after BMT for 2 years until relapse occurred, and was absent in one patient to 18 months after BMT. We have shown that PCR can detect the bcr-abl gene of CML using material from glass-slide smears. This technique may be useful as a general approach in evaluating archival hematologic specimens for the expression of critical gene products. PMID- 2196816 TI - A morphometric study of normodense and hypodense human eosinophils that are derived in vivo and in vitro. AB - Hypodense eosinophils were obtained from two patients with the idiopathic hyperosinophilic syndrome (IHES), and hypodense eosinophils were derived by culturing normodense human eosinophils from control donors in the presence of endothelial cells alone, granulocyte/macrophage-colony-stimulating factor (GM CSF) alone, or GM-CSF and fibroblasts. These eosinophils were examined ultrastructurally and stereologically for alterations in the volume density (Vv) of their electron-dense granules, the Vv of their lucent granules, the Vv of their lipid droplets, the numerical density of their granules with respect to cytoplasm (Nv), and the plasma membrane surface area-to-cell volume ratio (Sv) that might account for their decreased sedimentation density. The hypodense eosinophils that were obtained from the two patients with IHES exhibited a one third reduction in granule Vv relative to normodense eosinophils from control donors, primarily because of a decrease in granule size. The culture-derived hypodense eosinophils exhibited 10% to 16% decreases in their granule Vv, significant increases in their lucent granules, and a approximately 7.5% decrease in their Sv. Calculation of the cell volume from cross-sectional area measurements showed that the eosinophils that had been cocultured with fibroblasts in the presence of GM-CSF increased their volume by approximately 15%. The eosinophils that had been cocultured with endothelial cells exocytosed some of their granules. In conclusion, a composite of factors including cell swelling, a decrease in the volume of the cytoplasm occupied by granules, and an increase in granule lucency contributes to the hypodense phenotype in vitro, but only cell swelling and hypogranulation are seen in cells from patients with IHES. The latter could reflect the response of 'primed' hypodense eosinophils in vivo to pertinent tissue ligands. PMID- 2196815 TI - Loss and rearrangement of glomerular basement membrane laminin during acute nephrotoxic nephritis in the rat. AB - Many earlier studies have shown that the intravenous injection into rats of sheep antibodies against rat glomerular basement membrane (GBM) induces a rapid influx of neutrophils and proteinuria (nephrotoxic nephritis or NTN). The GBM antigens recognized by nephrotoxic antibodies (NTAbs) have not been identified conclusively. Our experiments presented here, however, showed that NTAbs did not significantly reduce binding of anti-laminin IgGs to laminin-coated enzyme-linked immunosorbent assay (ELISA) plates or to the GBM in vivo, indicating little cross reactivity between the NTAbs and laminin. To evaluate possible changes in GBM architecture during acute stages of NTN, the ultrastructural distribution of laminin was determined by postfixation, postembedding immunogold labeling, and compared between normal and nephritic rats. The density of immunoreactive GBM laminin was significantly reduced in rats with acute NTN. In addition, conjugates of anti-laminin IgG and horseradish peroxidase were intravenously injected into rats that then received injections of NTAbs. Anti-laminin peroxidase conjugates were also injected after administering NTAbs. In both cases, an overall decrease in anti-laminin peroxidase reaction product was observed as compared to normal controls. The densest labeling was seen in the lamina rara interna, especially in areas of endothelial cell detachment. Some immunoperoxidase reaction product was also bound to basal surfaces of detaching endothelial cells, demonstrating the removal of at least some laminin from the GBM. A decrease in GBM binding of intravenously injected anti-laminin IgG, both before and after injection of rats with NTAbs, was also confirmed by postembedding immunogold labeling. Furthermore, morphometry showed that the GBM was significantly wider in nephritic rats than in controls, indicating a redistribution of laminin over a greatly increased area. These immunoultrastructural findings show, therefore, that GBM architecture is altered in the early phase of NTN. PMID- 2196817 TI - Synthesis of chromogranin A, dopamine beta-hydroxylase, and chromaffin vesicles. AB - Primary cultures of bovine adrenal medullary cells synthesize chromogranin A (CgA) and dopamine beta-hydroxylase (DBH) and incorporate them into chromaffin vesicles. The incorporation of L-[35S]methionine into CgA, DBH, and total protein was approximately linear for 8 h at methionine concentrations of 12.5, 25, and 50 microM. Newly synthesized CgA and DBH were initially incorporated into vesicles of low buoyant density that matured over 24 h into vesicles having the greater buoyant density of chromaffin vesicles. Approximately 10% of the newly synthesized CgA is released constitutively within 4 h of formation, approximately 30-40% appears to be degraded, and the remainder is incorporated into chromaffin vesicles, which can secrete CgA in response to nicotinic stimulation. Newly synthesized DBH follows a similar course. Once incorporated into chromaffin vesicles, the newly synthesized CgA and DBH appear to be stable for 2-3 days and then decline with a half-time of 3-4 days. Primary cultures of bovine adrenal medullary cells are a good model system for studying factors regulating CgA and DBH synthesis and the formation of chromaffin vesicles. PMID- 2196818 TI - Calcium and the heat-shock response in the human monocytic line U-937. AB - In the human monocytic line U-937, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] increases cytosolic free calcium concentration ([Ca2+]i). 1,25-(OH)2D3 also enhances the synthesis of heat-shock proteins (HSPs) when U-937 cells are exposed to elevated temperatures. To establish whether these two effects of 1,25-(OH)2D3 are related, we examined the effects of calcium on the heat-shock (HS) response, as well as the influence of 1,25-(OH)2D3 on this system. The equilibrium dissociation constant (Kd) of the fluorescent probe used to measure [Ca2+]i, fura 2, at 37 and 45 degrees C was found to be 191 and 234 nM, respectively. Exposure of U-937 cells to 45 degrees C did not increase [Ca2+]i under conditions in which active efflux of the dye was prevented by the organic anion transport inhibitor probenecid (1 mM). In cells preincubated in calcium-free medium, with subsequent addition of 4 mM EGTA before HS, or exposed to the calmodulin antagonist N-(6 aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7), the increase in HSPs synthesis was not affected. Cell viability, assessed by [3H]thymidine uptake, was not different between cells exposed to HS in calcium-containing or calcium-free media. Moreover, the effects of 1,25-(OH)2D3 on the HS response were also observed in a calcium-depleted medium, indicating that the effects of 1,25 (OH)2D3 on HSP synthesis were not mediated by [Ca2+]i. PMID- 2196819 TI - Peptide transport systems for opiates across the blood-brain barrier. AB - Opiate peptides administered on one side of the blood-brain barrier can exert powerful effects on processes occurring on the other side. There is evidence for direct passage of opiate peptides and their analogues across this barrier. Beta Endorphin can enter the cerebrospinal fluid after systemic administration, but its entry into brain tissue has been more difficult to demonstrate, even though analogues enter at a modest rate. Enkephalins enter and exit the central nervous system as intact molecules by a combination of saturable and nonsaturable mechanisms. A family of transport systems may exist with varying affinities for the opiate enkephalins, antiopiates like tyrosine melanocyte-stimulating hormone inhibitory factor 1 (Tyr-MIF-1), and related peptides. The major system transporting these peptides, termed Peptide transport system 1, can be influenced by several factors with entry and exit rates affected by aging, drugs, amino acids, monoamines, aluminum, stress, and ethanol addiction and withdrawal. The homeostatic role of the blood-brain barrier thus extends to the regulation of the bidirectional transport of informational peptides such as the opiates. PMID- 2196820 TI - Ketone bodies and islet function: 45Ca handling, insulin synthesis, and release. AB - D-(-)-beta-Hydroxybutyrate and acetoacetate cause a rapid, sustained, and rapidly reversible stimulation of insulin release from rat pancreatic islets incubated in the presence, but not absence, of D-glucose. This coincides with stimulation of both proinsulin biosynthesis and 45Ca net uptake. The ketone bodies also decrease 45Ca outflow from prelabeled islets perifused in the absence of Ca2+ and, in contrast, enhance effluent radioactivity in the presence of Ca2+. In the presence of D-glucose, the secretory response to D-(-)-beta-hydroxybutyrate is concentration related in the 2.5-20 mM range, abolished in the absence of Ca2+ or presence of KCN, and enhanced by theophylline and forskolin. It corresponds grossly to a shift to the left of the sigmoidal curve relating insulin output to the ambient concentration of D-glucose. The secretory, biosynthetic, and cationic response to acetoacetate is less marked than that evoked by an equimolar concentration of D-(-)-beta-hydroxybutyrate. These features are compatible with the view that the insulinotropic action of ketone bodies would be causally linked to their metabolism in islet cells. PMID- 2196821 TI - Ketone bodies and islet function: 86Rb handling and metabolic data. AB - The metabolism of ketone bodies was investigated in rat pancreatic islets incubated in the absence or presence of D-glucose. The generation of 14CO2 from 3 14C-labeled ketone bodies, the interconversion of D-(-)-beta-hydroxybutyrate and acetoacetate (AcAc), the reciprocal effects of ketone bodies and D-glucose on their respective catabolism, and the influence of these exogenous nutrients on the output of 14CO2 from islets preincubated with either L-[U-14C]glutamine or [U 14C]palmitate provided an estimation of the nutrient-induced changes in O2 uptake that was in fair agreement with the observed modifications of islet respiration. There was a close correlation between such changes and the corresponding values for insulin output. Because the stimulation of insulin release by ketone bodies also coincided with a decrease in 86Rb outflow from prelabeled islets, these findings suggest that the insulinotropic action of ketone bodies is causally linked to their catabolism through an increase in ATP generation rate and a subsequent decrease in K+ conductance. A complementary participation of changes in mitochondrial redox state to stimulus-secretion coupling is considered, however, in the light of comparisons between the effects of D-(-)-beta hydroxybutyrate and AcAc, respectively, on mitochondrial NADH generation, 45Ca net uptake, and D-[6-14C]glucose oxidation. PMID- 2196822 TI - Influence of age and endurance training on metabolic rate and hormones in healthy men. AB - The associations among age, maximal aerobic capacity (VO2max), and body composition with resting metabolic rate (RMR), and fasting plasma hormones were examined in endurance-trained and untrained older and younger men. A higher RMR (approximately 6%; P less than 0.05), normalized per kilogram of fat-free weight (FFW), was found in endurance-trained younger and older men relative to untrained men. VO2max, independent of FFW, accounted for a significant portion of the variation in RMR. Fasting insulin and the fasting insulin-to-glucose ratio were higher in older men relative to younger men. This difference was diminished when differences in percent body fat were taken into account. Plasma thyroid hormones and glucagon were not associated with age, VO2max, or percent body fat. We conclude that endurance-trained and older men have a higher RMR than untrained younger and older men that is independent of differences in FFW. Plasma levels of thyroid hormones and glucagon are not influenced by age, VO2max, or adiposity in healthy nonobese men. PMID- 2196823 TI - Effects of insulin on whole body and forearm leucine and KIC metabolism in type 1 diabetes. AB - To investigate whole body rates of appearance (Ra) and forearm metabolism of leucine and alpha-ketoisocaproate (KIC) in type 1 diabetes, before and after insulin administration, seven diabetic subjects were studied in the postabsorptive state with primed-constant infusions of L-[4,5-3H]leucine and [1 14C]KIC, and forearm arterial deep-venous catheterization. This combined technique allowed the selective quantitation of the two processes regulating forearm leucine and KIC metabolism (release and uptake) that may occur simultaneously. Before insulin (arterial plasma glucose, 284 +/- 24 mg/dl; leucine, 215 +/- 24 mumol/l; KIC, 42 +/- 3 mumol/l) forearm leucine and KIC release exceeded uptake slightly but significantly (P less than 0.05). During a 180-min insulin infusion, arterial glucose (144 +/- 27 mg/dl) and leucine concentrations (130 +/- 15 mumol/l) decreased (P less than 0.05 or less vs. base line) toward normal, whereas KIC did not change (33 +/- 4 mumol/l, NS). However, no net uptake of either leucine or KIC across the forearm was detected at any time point. In contrast, a significant net release of these substrates occurred throughout the insulin infusion. By the end of the hormone administration, whole body leucine and KIC Ra decreased 17 and 33%, respectively (P less than 0.01). However, forearm uptake and release of leucine and KIC did not significantly change with respect to base line. The fraction of whole body leucine released from estimated total muscle mass did not change (54 to 48%, NS) before vs. after insulin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2196824 TI - A rapid in vitro test for chloroquine-resistant Plasmodium falciparum. AB - We report a rapid (2-3 hr) in vitro test for chloroquine resistance in Plasmodium falciparum. The test is based on the inhibition of chloroquine efflux by verapamil; it is performed by diluting infected blood in culture medium and incubating the diluted blood for 60 min at 37 degrees C with 50 nM 3H chloroquine, with and without 10 microM verapamil. The test can be performed with the ring stage parasites in the blood of infected patients and in the presence of white cells, platelets and anticoagulants (heparin, EDTA, or citrate). Although the test can be performed in triplicate with 20 microliters of blood and specimens may be kept in anticoagulants at 4 degrees C for up to 24 hr, parasitemias less than 0.1% limit the sensitivity of the assay. Inhibition of chloroquine efflux by verapamil may permit the rapid identification of chloroquine resistant P. falciparum in blood specimens from infected patients. PMID- 2196825 TI - Comparison of Dot-ELISA with Sandwich-ELISA for the detection of circulating antigens in patients with bancroftian filariasis. AB - We compared the performance of a newly developed Dot-ELISA with that of a previously described Sandwich-ELISA to detect parasite antigens in sera from patients with bancroftian filariasis. The same monoclonal antibody and the same sera were used in both tests. In the Dot-ELISA, 67 of 70 sera from microfilaremic donors were deemed to contain filarial antigens when screened at a dilution of 1:50. End titers were 1:80-1:1280. With the Sandwich-ELISA, 64 of the same sera were positive at a dilution of 1:10 and 42 were positive at a dilution of 1:50. End titers were 1:10-1:320. The specificity of both assays was greater than 95%, but their sensitivity was remarkably different. The Dot-ELISA could detect as little as 0.055 ng/ml microfilarial antigen added to normal human sera, whereas the lower limit with the Sandwich-ELISA was 10 ng/ml parasite antigen. Additionally, the Dot-ELISA does not require radioactivity or sophisticated equipment and, therefore, can be performed in virtually all filariasis-endemic areas. PMID- 2196826 TI - [The indirect echographic signs in the prenatal diagnosis of spina bifida aperta in the second trimester of pregnancy. A report on 2 cases]. AB - The authors present a brief literary review on the frequency and etiological factors of the opened spinal dysraphism. The importance of its echographic diagnosis is indicated by using indirect signs, mainly microcephaly, ventriculomegaly, cerebellar pathology ("a sign of the banana") and characteristic fronto-temporal configuration of the fetal encephalic cranium ("a sign of the lemon") up to 24 week's of gestation. Two cases of diagnosed spinal dysraphism during the second trimester of pregnancy with established indirect echographic signs, promoting active search for direct echographic image of this congenital defect of the neural tube, are described. PMID- 2196827 TI - [The therapeutic aspect and management in condylomata acuminata]. PMID- 2196828 TI - [Doppler study of the fetal and uteroplacental blood flows in normal pregnancy]. AB - The Doppler examination of the fetal and uteroplacental blood flow established that the mean velocity of the blood flow in the fetal aorta was 32.46 +/- 2.13 cm/s, in the arcuate artery--60.46 +/- 10.75 cm/s, in the umbilical artery--33.54 +/- 7.14 cm/s, but in the umbilical vena--15.83 +/- 1.00 cm/s. It was indicated that the volume of the blood flow of the fetal aorta in ml/min was increased with advancement of the gestational age, but it remained relatively constant during pregnancy when it was estimated in ml/min/kg. The characteristic of Doppler wave of the fetal aorta as well as of the umbilical artery and arcuate artery were analysed. It is pointed out that the Doppler examination of the fetal and uteroplacental blood flow is a new, noninvasive, valuable and objective method in the diagnosis of the fetal state. PMID- 2196829 TI - [The current principles of the surgical and combined treatments of cancer of the cervix uteri at the 1st clinical stage]. PMID- 2196831 TI - Detection of glycoproteins separated by nondenaturing polyacrylamide gel electrophoresis using the periodic acid-Schiff stain. AB - We observed that published methods for staining glycoproteins in sodium dodecyl sulfate-polyacrylamide gels did not stain glycoproteins separated by nondenaturing polyacrylamide gel electrophoresis. Therefore, the periodic acid Schiff stain for glycoprotein was adapted for use with proteins analyzed by nondenaturing polyacrylamide gel electrophoresis. Following nondenaturing polyacrylamide gel electrophoresis proteins were denatured in situ by incubation with aqueous 2% sodium dodecyl sulfate, 5% 2-mercaptoethanol, 40% ethanol, and 5% acetic acid at 90 degrees C for 15 min followed by periodic acid-Schiff staining. This modified procedure will detect at least 0.2 micrograms protein-associated carbohydrate. Omission of the periodic acid treatment from the protocol was used as a control to detect nonspecific staining of some proteins. This modified procedure was validated using both purified glycoproteins and extracellular culture fluid containing carbohydrate-associated proteins of Ruminococcus flavefaciens. PMID- 2196830 TI - DNA contents of replication without DNA density labeling. AB - A new method for determining the timing of DNA replication in specific regions of the mammalian genome without the use of DNA density labeling and DNA density centrifugation is described. The method is based on determination of average relative DNA copy numbers in specific genomic regions as cells progress through S phase, and "time of replication" for a specific region is described in terms of the cell's DNA content when the region is replicated. DNA is isolated from synchronized populations of G1 and S phase cells, it is slot-blotted at the same DNA concentration(s) for each population, and it is hybridized with 32P-labeled DNA probes that are specific to the regions of interest. Quantitation of the slot blot autoradiograms and flow cytometric analysis allows determination of (a) average relative DNA copy numbers for the regions of interest in synchronized cell populations, and (b) the average total DNA content in each population of synchronized cells. This information and the flow cytometry histograms are then used to calculate the cellular DNA content at which each region of interest is replicated. The results have a precision of less than or equal to +/- 10% of S phase for Chinese hamster (line CHO) rhodopsin, metallothionein II, the 5'-end of dihydrofolate reductase, the telomeric repeated sequence, pHuR-093 (also located near the centromeres in CHO chromosomes), and the c-Ki-ras family. PMID- 2196832 TI - Nuclear magnetic resonance spectroscopy. PMID- 2196833 TI - Mass spectrometry. PMID- 2196834 TI - Liquid chromatography: theory and methodology. PMID- 2196835 TI - DNA amplification by the polymerase chain reaction. AB - The polymerase chain reaction (PCR) is a technique involving enzymatic amplification of nucleic acid sequences via repeated cycles of denaturation, oligonucleotide annealing, and DNA polymerase extension. PCR has revolutionized the practice of DNA technology as it allows virtually any nucleic acid sequence to be readily generated in vitro in relatively great abundance, so that subsequent analyses are not confounded by the presence of other DNA fragments or a lack of material with which to work. PCR also enables the sequence of individual DNA fragments to be altered. The method has advantages over conventional procedures for DNA cloning and analysis in many circumstances because it is faster, simpler, and more flexible. The total range and number of applications that have evolved in the short time since the first report of PCR are enormous. This review describes some of the history of PCR, the principle of the method, practical considerations for performing PCR, and a variety of applications. PMID- 2196837 TI - Development of the dorsal pancreatic primordium transplanted into the third ventricle of rats. AB - The dorsal pancreatic primordia of 12.5-day-old rat embryos transplanted into the third ventricle of adult female rats were immunohistochemically examined 10, 20 and 40 days after transplantation. On day 10, the grafts grew into an epithelial sacculus (S) with a thick subepithelial tissue (ST). Tubular and vesicular structures with a single cuboidal epithelium were found within the wall of the S, but they underwent thereafter a regression without allowing the primordia to differentiate into the exocrine acinar tissues. In contrast with this, pancreatic hormone-containing cells existed in the ST, and were arranged like the islands of a mature animal. The tissue also has smooth muscle fibers and neurons. When the primordium was grafted along with its root connected to the duodenum, gut-like tubular structures differentiated, showing mucosa with villi and crypts, submucous mesenchymal tissue and muscle layers. The mucosa possesses epithelial cells immunoreactive for the pancreatic hormones, and the muscle layers have the myenteric plexuses. These findings seem to provide further evidence that in the rat pancreas, pancreatic-hormone-containing cells differ from the acinar cells in origin. PMID- 2196836 TI - The parvalbumin-containing nonpyramidal neurons in the rat hippocampus. AB - The calcium-binding protein parvalbumin is considered to be involved in the control of intracellular ion homeostasis of highly active inhibitory neurons. A review of the light and electron microscopical features as well as the identified synaptic connections of these neurons is presented. Parvalbumin-containing neurons are mostly located within or in the vicinity of the granule or pyramidal cell layer. They form a subgroup of GABAergic neurons that has a target specificity for the cell body region. Their fine structural characteristics are identical to those known for hippocampal inhibitory neurons. Parvalbumin containing neurons are involved in several inhibitory pathways: feed-back inhibition, feed-forward inhibition and disinhibition. The functional implications of our own as well as published data are discussed. Special consideration is given to the possible physiological role of parvalbumin in these neurons. PMID- 2196838 TI - Glycogen metabolism in cultured chick hepatocytes: a morphological study. AB - Ultrastructural and autoradiographic observations of cultured chick hepatocytes under the following conditions are described: Induction of glycogen synthesis with glucose alone and glucose plus insulin, and glucagon-induced glycogen breakdown. Profiles of hepatocytes cultured in medium containing 10 mM glucose showed typical cellular organelles and occasionally a few glycogen granules. After incubation of hepatocytes with 3H-glucose, silver grains were found over these sparse glycogen granules, indicating a low level of glycogen synthesis by a few cells. After addition of 75 mM glucose for 1 hr about 3% of the profiles of cells showed glycogen, and by 24 hr half of the hepatocytes had glycogen. Addition of insulin plus glucose induced glycogen synthesis in 82% of the cells after 6 hr, and by 24 hr almost every cellular profile showed glycogen particles. Morphologically, glycogen accumulation was similar whether the cells were stimulated by high glucose or by glucose plus insulin: glycogen granules appeared in restricted regions of the cytoplasm, which were rich in smooth endoplasmic reticulum (SER), and peroxisomes were found close to the newly deposited glycogen particles. At maximum glycogen accumulation the association of SER and peroxisomes with glycogen was less obvious. Glycogenolysis induced by incubation of glycogen-rich hepatocytes with glucagon resulted in proliferation of SER in the glycogen regions of the cells. These observations are compatible with the concept of regions in the hepatocyte cytoplasm specialized for glycogen metabolism. Possible roles for SER and peroxisomes found near glycogen particles and other organelles in hepatic glycogen metabolism are discussed. PMID- 2196839 TI - Ultrasound investigation of fetal human upper respiratory anatomy. AB - Although the human upper respiratory-upper digestive tract is an area of vital importance, relatively little is known about either the structural or functional changes that occur in the region during the fetal period. While investigations in our laboratory have begun to chart these changes through the use of postmortem materials, in vivo studies have been rarely attempted. This study combines ultrasonography with new applications of video editing to examine aspects of prenatal upper respiratory development. Structures of the fetal upper respiratory digestive tract and their movements were studied through the use of ultrasonography and detailed frame-by-frame analysis. Twenty-five living fetuses, aged 18-36 weeks gestation, were studied in utero during routine diagnostic ultrasound examination. These real-time linear array sonograms were videotaped during each study. Videotapes were next analyzed for anatomical structures and movement patterns, played back through the ultrasound machine in normal speed, and then examined with a frame-by-frame video editor (FFVE) to identify structures and movements. Still images were photographed directly from the video monitor using a 35 mm camera. Results show that upper respiratory and digestive structures, as well as their movements, could be seen clearly during normal speed and repeat frame-by-frame analysis. Major structures that could be identified in the majority of subjects included trachea in 20 of 25 fetuses (80%); larynx, 76%; pharynx, 76%. Smaller structures were more variable, but were nevertheless observed on both sagittal and coronal section: piriform sinuses, 76%; thyroid cartilage, 36%; cricoid cartilage, 32%; and epiglottis, 16%. Movements of structures could also be seen and were those typically observed in connection with swallowing: fluttering tongue movements, changes in pharyngeal shape, and passage of a bolus via the piriform sinuses to esophagus. Fetal swallows had minimal laryngeal motion. This study represents the first time that the appearance of upper airway and digestive tract structures have been quantified in conjunction with their movements in the living fetus. PMID- 2196840 TI - [Acute necrotizing hemorrhagic pancreatitis]. AB - There is no etiologic treatment for acute necrotizing pancreatitis. Advances in intensive care resulted in a reduction in early death rate by a better control of systemic complications. Delayed death rate from infection is high (20-60%). Diagnostic problems are an important cause, in spite of the aid of computed tomography and echography. The prognosis will further be improved by earlier diagnosis, a better definition of surgical treatment when complications arise, and constant medicosurgical collaboration. PMID- 2196841 TI - [Central anticholinergic syndrome during postoperative period]. AB - The central anticholinergic syndrome (CAS) includes central signs (somnolence, confusion, amnesia, agitation, hallucinations, dysarthria, ataxia, delirium, stupor, coma) and peripheral signs (dry mouth, dry skin, tachycardia, visual disturbances and difficulty in micturition). It occurs when central cholinergic sites are occupied by specific drugs and also as a result of an insufficient release of acetylcholine. The CAS can be caused by atropine sulphate, hyoscine (scopolamine), promethazine, benzodiazepines, opioids, halothane, influrane, ketamine. The incidence of CAS during the postoperative period depends on choice and dose of anaesthetic agents, type of surgery, patient's condition and diagnostic criteria. It is close to 10% following general anaesthesia and 4% following regional anaesthesia with sedation. The differential diagnosis of CAS includes an overdose of anaesthetic drugs or an alteration in pharmacokinetics, altered hydratation, electrolyte or acid-base state, hypoglycaemia, hypoxia, hypercapnia, hypocapnia, hyperthermia, hypothermia, hormonal disorders, neurological damage resulting from surgery, embolism, haemorrhage or trauma. The diagnosis of CAS is often determined by a process of exclusion and not actually made until a positive therapeutic response to physostigmine, a centrally active anticholinesterase agent has taken place. PMID- 2196842 TI - [Fatal Lyell's syndrome caused by griseofulvin]. AB - A case of toxic epidermolysis (TE) with a fatal outcome is reported. It occurred after administration of 500 mg griseofulvin twice daily in a 19-year-old female patient. She developed the first skin lesions on the sixth day of treatment. All the body surface was involved, except for the scalp. Several complications arose in the course of the disease, thrombocytopaenia, lymphocytopaenia, rhabdomyolysis, and non cardiogenic pulmonary oedema. Death occurred as a result of multiple organ failure following septic shock associated with adult respiratory distress syndrome. The pathogenesis of these complications and the major therapeutic difficulties encountered are discussed. The involvement of griseofulvin in TE has only been reported once before. The arguments in favour of its involvement in the present case are discussed. PMID- 2196843 TI - [Consensus development conferences in intensive care medicine. V conference: diagnosis of nosocomial pneumonia in resuscitation. (Bicetre University Hospital Center, Paris, October 13, 1989)]. PMID- 2196844 TI - Group B Streptococcus hemorrhagic tonsillopharyngitis. PMID- 2196845 TI - Occupational hygiene aspects of biological monitoring. AB - Biological monitoring of workers exposed to toxic substances has been used for many years for a variety of differing purposes. This has caused some confusion amongst the professions concerned as to its proper use in any defined circumstances. This paper attempts to clarify the position, particularly as regards the role of biological monitoring in occupational hygiene practice. PMID- 2196846 TI - A review of the health effects of hydrogen sulphide exposure. PMID- 2196847 TI - [Preoperative imaging in primary hyperparathyroidism before first cervicotomy]. AB - A primary neck exploration for primary hyperparathyroidism can be performed without any previous morphological investigations. However, ultrasonography, CT scan and thallium technetium isotope scan can facilitate the surgical procedure as they frequently reveal and localize a parathyroid adenoma, due to the frequently large size of most adenomas. Although not all of these morphological investigations are always successful, we strongly recommend the use, in particular, of ultrasonography which is a non-invasive and inexpensive method. The other investigations, which are more expensive and less widely available can be discussed for each individual patient. These morphological investigations are obviously indicated in persistent recurrent primary hyperparathyroidism. PMID- 2196848 TI - [First cervicotomy for primary hyperparathyroidism. Argument against preoperative imaging]. AB - The sensitivity of various pre-operative imaging methods for enlarged parathyroid glands ranges between 40 and 80%. These dismal results can be explained by the limits of resolution and uneven specificity of the methods and by parathyroid ectopias. Conversely, in primary hyperparathyroidism (PHT), multiple gland enlargement occurs in 12-30% of cases and therefore, even a positive imaging study can overlook a second enlarged gland. A prospective study conducted in 34 patients, all successfully operated, confirmed the lack of value of pre-operative imaging before a first neck exploration, with a sensitivity of 33 to 80%, depending on the method. PMID- 2196849 TI - The problem of the taxonomy of the fusiform bacillus of acute necrotizing ulcerative gingivitis (Vincent's gingivitis). AB - The characteristic microscopic appearance of the fusospirochaetal complex in smears from patients with acute necrotizing ulcerative gingivitis has long been regarded as virtually pathognomonic of the disease. Unfortunately there is considerable confusion surrounding the taxonomy of the fusiform organism in the fusospirochaetal complex. The conflicting views appear to be irreconcilable and a re-evaluation of the taxonomy of oral fusiforms is urgently required. PMID- 2196850 TI - Polydipsia in the chronically mentally ill: a review. AB - Polydipsia, or excessive intake of water, is reviewed in the chronically mentally ill from a nursing perspective. The purpose of this article is to review research related to excessive water ingestion, the magnitude and types of problems that these patients experience, and the treatment interventions reported. Future research and practice should focus on understanding the patient's experience of polydipsia and how it relates to the patient's level of functioning, testing assessment tools, and determining appropriate interventions. PMID- 2196851 TI - The paranoid person: a biopsychosocial perspective. AB - Paranoia is not a uniquely medical term. Articles on the subject appear in the literature of fields as diverse as psychology, sociology, linguistics, cognitive processing, and computers. Paranoia is also a human response to physical, psychical, interpersonal, and social ills and, as such, is a phenomenon of interest to nursing. The study of paranoia by several disciplines provides nurses with a variety of perspectives from which to understand the experiences of paranoid clients. Paranoia will be presented as a phenomenon that can be viewed from levels ranging from the suborganismic level to the sociocultural. Implications for nursing interventions geared to each level will be discussed. PMID- 2196852 TI - Seasonal affective disorder, the depression of winter: a literature review and description from a nursing perspective. AB - This article presents a literature review and description of seasonal affective disorder (SAD). SAD is a newly recognized disorder, differentiated from other affective illnesses by its seasonality (with midwinter dysthymia and spring/summer remission), and its atypical symptoms of hypersomnia and hyperphagia. SAD symptoms remit with travel towards the equator or with bright light treatments, possibly indicating a chronobiological circadian etiology. This article introduces aspects of SAD that are amenable to the nursing process, including assessment of the seasonality of dysthymic symptoms; diagnoses of patient responses; referral, education, and psychotherapeutic interventions; and evaluation of patient responses to interventions. Since SAD is found predominantly in young women, and because symptoms may be exacerbated by rotating shifts, it is possible that nurses may have a higher incidence of SAD, compared with other professions. PMID- 2196853 TI - Nonadrenergic, noncholinergic control of mucus secretion in the airways. PMID- 2196854 TI - Mechanisms of purine-induced bronchoconstriction in asthma. PMID- 2196855 TI - The human pharmacology of capsaicin. PMID- 2196856 TI - Capsaicin-sensitive nerves in the gastrointestinal tract. PMID- 2196857 TI - Central organization of the vagal drive to the nonadrenergic, noncholinergic neurones controlling gastric motility. PMID- 2196858 TI - Regulation of the peristaltic reflex by peptides of the myenteric plexus. PMID- 2196859 TI - Peptidergic mechanisms in the pancreas. PMID- 2196860 TI - P1- and P2-purinoceptor subtypes--an update. AB - It is suggested that neither the P1- nor the P2-purinoceptor forms a homogeneous group and that each can be separated into at least two subtypes. Biochemical, ligand binding and pharmacological studies clearly indicate that the P1 purinoceptor can be subdivided into the A1- and A2-subtypes. The recent development of antagonists, selective for the A1-subtype, supports this conclusion. Evidence for an A3-receptor also exists. On the basis of the rank order of potency of structural analogues of ATP and on the activity of antagonists, it is suggested that the P2-purinoceptor may be divided into the P2x and P2y-subtypes. beta,gamma-methylene-L-ATP is a specific agonist at the P2x subtype and ADP-beta-F a specific agonist at the P2y-subtype. Suramin acts as an antagonist at both subtypes, but reactive blue 2 appears to display selectivity for the P2y-purinoceptor. There is also evidence for P2t- and P2z-purinoceptors. PMID- 2196861 TI - Neurogenic inflammation in airways and its modulation. PMID- 2196862 TI - The NANC system and airway vasculature. AB - The different structures of the nasal, tracheal and bronchial vascular beds are described. All the vasculatures are influenced by neuropeptides released from three types of nerve: (1) sympathetic nerves release both noradrenaline and neuropeptide Y (NPY), both of which cause vasoconstriction; (2) parasympathetic nerves release both acetylcholine and either vasoactive intestinal polypeptide (VIP), peptide histidine methionine (PHM) or peptide histidine isoleucine (PHI), all of which cause vasodilatation; and (3) sensory nerves release sensory neuropeptides such as substance P (SP), calcitonin gene-related peptide (CGRP) and neurokinins A and B (NKA, NKB). Direct application of the neuropeptides to various preparations of the vascular beds confirms their actions. Stimulation of nerves to the airways in vivo causes vascular changes in the presence of anti acetylcholine, anti-noradrenaline and ganglionic-blocking drugs, suggesting that they are mediated by neuropeptides. Reflex activation of the parasympathetic and sympathetic nerves to the airway vasculature has been established, but the relative importance of classical neurotransmitters and of neuropeptides has not been analyzed. The neuropeptides in sensory nerves are released when the nerves are stimulated by capsaicin, various chemical irritants and inflammatory mediators such as histamine and bradykinin. The sensory neuropeptides cause not only vasodilatation but also, in some instances, extravasation of plasma protein and an increase in interstitial fluid volume. The interaction of the different neuropeptide systems, and their interplay with classical transmitters released from motor nerves, require further exploration. PMID- 2196863 TI - The Cd-Chelex assay: a new sensitive method to determine metallothionein containing zinc and cadmium. AB - A rapid and sensitive one-vial procedure to determine metallothionein (MT) containing zinc (Zn) and cadmium (Cd) is described. New features of this Cd saturation method are: high molecular weight Cd-binding proteins are denatured by treatment with acetonitrile (50% final concentration), and excess of Cd is bound to a cation exchange resin (Chelex-100). With this method, MT has been measured, e.g. in liver of control and zinc- or cadmium-treated rats, in human liver and in cultured human fibroblasts down to absolute amounts of 0.1 microgram. The Cd Chelex assay is 10 times more sensitive than the established Cd-heme assay (Dieter et al. 1986) and therefore is particularly suitable to quantify MT in small tissue samples (e.g., liver biopsies of a few milligrams) and in extrahepatic tissues or cell cultures with low MT concentrations. PMID- 2196864 TI - Spectrophotometric determination of pyrrole-like substances in urine of rat and man: an assay for the evaluation of 2,5-hexanedione formed from n-hexane. AB - Male Wistar rats exposed to atmospheric n-hexane excreted in their urine substances which gave rise to absorption spectra like those of pyrroles after the reaction with Ehrlich's reagent. A simple spectrophotometric assay was developed to determine these "pyrrole-like substances" in urine. Their excretion kinetics were evaluated by exposing rats for 8 h to atmospheric n-hexane concentrations between 50 and 3000 ppm. The dose-response curve revealed saturation kinetics according to Michaelis-Menten, Vmax being 1.12 [delta E526.ml urine/8 h n-hexane exposure] and "Km", the atmospheric n-hexane concentration at Vmax/2, being 250 ppm. The excretion of pyrrole-like substances closely correlated with that of 2,5 hexanedione measured by Fedtke and Bolt (1987). Pyrrole-like substances were also found in the urine of a male volunteer. When exposing the person for 3 h to atmospheric n-hexane at a concentration of 146 ppm (equivalent to 55 ppm/8 h) the excreted amount was twice the background value. Due to the sensitivity of this assay it is possible to determine pyrrole-like substances in urine according to the present German MAK or US TLV conditions for n-hexane (50 ppm/8 h). PMID- 2196865 TI - Protease activity in gingival crevicular fluid from discrete periodontal sites in humans with periodontitis or gingivitis. AB - Sensitive fluorogenic assays were used to compare the protease activities of fluid collected from eight such sites in each of 21 adult patients with gingivitis and 22 with periodontitis. The degradation of N-carbobenzoxy-gly-gly arginine-AMC, L-arginine-AMC, glyproline-AMC, L-leucine-AMC, N-alpha-benzoyl-L arginine-AMC, N-[p-toluenesulphonyl]-gly-pro-arginine-AMC, N-tert-butoxycarbonyl leu-ser-thr-arginine-AMC, N-tert-butoxycarbonyl-ileu-glut-gly-arginine-AMC and N tert-butoxycarbonyl-val-leu-lysine-AMC was significantly greater by fluid from the periodontitis group. The specific rates of degradation of L-arginine-AMC, gly proline-AMC, N-alpha-benzoyl-L-arginine-AMC and N-[p-toluene-sulphonyl]gly-pro arginine-AMC were significantly greater in that group, indicating that the composition of their gingival crevicular fluid was different from that of the gingivitis group. Discriminant analysis of the substrate hydrolysis data alone correctly identified 77.6% of sites with sensitivity and specificity values of 73.3 and 82.1%, respectively. The predictive value of these assays requires further investigation, but it is possible that they will prove useful for monitoring the success of periodontal treatment. PMID- 2196866 TI - Early hominid dental pathology: interproximal caries in 1.5 million-year-old Paranthropus robustus from Swartkrans. AB - Carious lesions on the mesial and distal aspects of a RM1 of a young adult 'robust' australopithecine. Paranthropus robustus, are described. The specimen is from Member 1 sediments of the Swartkrans cave, which are dated to between about 1.8 and 1.5 million years before present. The mesial lesion, located cervically, had progressed further than the two distal lesions, which were situated along the cervix and in the enamel of the interproximal contact facet. This is the third specimen of P. robustus to be discovered with dental caries, but the other two cases were associated with occlusal and buccal enamel hypoplasia. Caries is present in less than about 3.0% of the approx. 116-128 P. robustus specimens at Swartkrans, and this incidence is noticeably lower than in the small Homo erectus sample from the same site. While this difference may simply be a sampling artefact, it may reflect dietary differences between these two synchronic and presumably sympatric early hominid species. PMID- 2196868 TI - Tumour necrosis factor alpha in gingival crevicular fluid as a possible indicator of periodontal disease in humans. AB - The suitability of using the cytokine TNF as an indicator of periodontal disease was assessed. Gingival crevicular fluid was collected from 162 sites on filter strips and analysed for TNF by ELISA. About 21% of the sites contained TNF: the amount recovered per site ranged from 0.2 to 998.8 fmol with a median value of 3.7 fmol. The periodontal disease status of each site was documented by recording the gingival and plaque indices, and by measuring pocket depth. About 62% of TNF containing sites had a gingival index of 1, 76% had a plaque index of 0 or 1, and 47% had pockets of 3 mm or less. When the periodontal status of sites with and without TNF was compared by chi 2 analysis, no significant differences were found. These findings suggest that TNF may be found in sites prior to clinically observable disease and therefore may prove to be a suitable indicator for periodontal disease. PMID- 2196867 TI - Comparison of pulpal blood flow in dog canine teeth determined by the laser Doppler and the 133xenon washout methods. AB - Pulpal blood flow measurements by laser Doppler flowmetry were compared with those made simultaneously and on the same teeth by the 133Xe washout method. Pulpal method flow in the resting state was 82.4 ml/min per 100 g as calculated from the fast component of the 133Xe washout, whereas laser Doppler flowmetry recorded 263 mV. The close intra-arterial (i.a.) injection of the vasoconstrictor norepinephrine (10(-2)-10(-1) micrograms/kg) caused a reduction of pulpal blood flow by 20.2% with the 133Xe washout and by 9.7% with the laser Doppler flowmetry in 6 observations in 4 dogs. The laser Doppler flowmetry measurements of these norepinephrine-induced changes correlated significantly with changes measured by the 133Xe washout method as analysed by linear regression (p = 0.004). PMID- 2196869 TI - Computer awareness. PMID- 2196870 TI - Bugs, bytes and blood pressure. PMID- 2196871 TI - Pulmonary toxicity following MOPP chemotherapy. AB - Pulmonary toxicity is a well recognised side effect of anticancer agents particularly bleomycin, cyclophosphamide, methotrexate, and busulphan. In contrast this problem has been infrequently reported following MOPP (nitrogen mustard, vincristine, prednisolone, procarbazine) chemotherapy for Hodgkin's disease and has been attributed principally to the procarbazine. We report a further instance of MOPP associated pulmonary toxicity. This case and a review of previously published cases indicate that MOPP chemotherapy may be associated with the development of permanent lung damage as well as an acute reversible hypersensitivity lung disease. PMID- 2196872 TI - Anti-neutrophil cytoplasm antibodies (ANCA). AB - Circulating antibodies directed against cytoplasmic constituents of granulocytes and monocytes (anti-neutrophil cytoplasm antibodies, ANCA) are found in about 80% of active cases of Wegener's granulomatosis and microscopic polyarteritis. Antibodies are detected by indirect immunofluorescence on normal peripheral blood leucocytes, or by ELISA or radio-immunoassay using a neutrophil cytoplasm extract. There are 2 patterns of staining seen on indirect immunofluorescent examination of leucocytes and a number of different molecules recognised on Western blots. In Wegener's granulomatosis diffusely granular cytoplasmic staining (cANCA) is associated with a 29KD molecule that has recently been identified as neutrophil proteinase 3. A finely granular pattern may also be seen in microscopic polyarteritis. A perinuclear pattern (pANCA) is present in some other cases of segmental necrotising glomerulonephritis and occasionally in rheumatoid arthritis but almost never in Wegener's granulomatosis. This pattern is often associated with the presence of anti-myeloperoxidase and anti-elastase antibodies. Levels of anti-neutrophil cytoplasm antibodies usually reflect disease activity but a pathogenetic role for these antibodies in the development of small vessel vasculitides is, as yet, unproven. PMID- 2196873 TI - Proarrhythmic actions of antiarrhythmic drugs: a review. AB - The ability of antiarrhythmic drugs to aggravate and even cause arrhythmias is now well-established. The incidence of such effects for a wide range of agents is of the order of 3-15%. The two major mechanisms are facilitation of reentry circuits and the production of triggered activity due to early after depolarisations. This latter effect probably underlies the drug-induced long QT syndromes and associated arrhythmias including 'torsade de pointes' and is more likely to occur in association with bradycardia, hypokalaemia, or concomitant digitalis therapy. While some or all of these mechanisms are capable of producing or aggravating both supraventricular and ventricular arrhythmias, this review deals only with 'proarrhythmic' effects in the ventricles. These are known to be more likely in the presence of poor ventricular function (left ventricular rejection fraction less than 35%). Optimal management may include withdrawal of antiarrhythmic agents, replacement of potassium, infusion of magnesium and overdrive pacing. PMID- 2196874 TI - Creutzfeldt-Jakob disease and slow infections: a review. PMID- 2196875 TI - Temperature dependence of transcriptional activity of yeast 3 phosphoglycerokinase promoter in Escherichia coli. AB - We have studied the activity of yeast PGK promoter in E. coli at different temperatures using lacZ as the reporter gene. The B-galactosidase activity was found to be less at 42 degrees C than at 30 degrees C. Northern blot analysis showed that the level of lacZ transcript was less in recombinant cells grown at 42 degrees C, whereas plasmid copy number per cell was more as compared to recombinant cells grown at 30 degrees C. Data suggest that the yeast PGK promoter is less active at 42 degrees C and that this activity is regulated at the level of transcription. PMID- 2196876 TI - Synthesis of a new helical protein: the effect of secondary structure rearrangement on structure formation. AB - A new helical protein was designed and synthesized to alter the sequential connectivity of the 4 helices in human growth hormone and to delete the long surface loop structures. The protein accumulated as an insoluble form in E. coli was solubilized and purified to apparent homogeneity in the presence of 7M urea, and refolded by the aid of 1% n-octyl-beta-D-glucopyranoside. The circular dichroism spectrum was typical of a highly helical protein. The molecular weight estimated by gel permeation chromatography and the red-shift of the fluorescence maximum by urea-induced denaturation suggest that the protein folds into a compact globular form. The new protein obtained, however, was destabilized relative to the original human growth hormone. PMID- 2196878 TI - Expression of a normal and variant Alzheimer's beta-protein gene in amyloid of hereditary cerebral hemorrhage, Dutch type: DNA and protein diagnostic assays. AB - Amyloid fibrils deposited in cerebral vessel walls in Dutch patients with hereditary cerebral hemorrhage with amyloidosis (HCHWA-D) are formed by polymerization of a 39-residue peptide similar to the beta-protein of Alzheimer's disease, Down syndrome, sporadic cerebral amyloid angiopathy and normal aging. Sequence analysis of genomic DNA in HCHWA-D patients demonstrated a point mutation, cytosine for guanine at position 1852 of the precursor beta-protein gene, which causes a single amino acid substitution (glutamine for glutamic acid) corresponding to position 22 of the amyloid protein. The normal allele was also present in these patients. To examine the expression of normal and variant beta protein alleles in HCHWA-D we analyzed all the tryptic peptides obtained from several amyloid fractions from leptomeningeal vascular walls. Amino acid sequence of two peptides (T3a and T3b) with identical amino acid composition revealed that T3a had glutamine and T3b had glutamic acid at position 22. Thus both the normal and variant Alzheimer's beta-protein alleles are expressed in vascular amyloid in HCHWA-D and may be detected by tryptic peptide mapping. Moreover, we have developed a diagnostic assay for high risk populations and prenatal evaluation that is based on the existence of the mutation. PMID- 2196877 TI - Evidence for Pro-dermorphin processing products in rat tissues. AB - Dermorphin (Tyr-D.Ala-Phe-Gly-Tyr-Pro-Ser-NH2) and dermenkephalin (Tyr-D.Met-Phe His-Leu-Met-Asp-NH2), two powerful opioid peptides issued from a common biosynthetic precursor, were recently isolated from the skin of the frog phyllomedusa sauvagii. Since many amphibian's skin secretory peptides or their homologues are found in the mammalian central nervous system and gastrointestinal tract, dermorphin and dermenkephalin may have counterparts in mammals. We have prepared antibodies directed against dermorphin, dermenkephalin and the spacer sequence lying between them in the progenitor form and developed sensitive enzyme immunoassays that detect under the picogram level to verify the occurrence of these peptides in rat tissues. Immunocytochemical studies of rat brain sections revealed a similar distribution of immunoreactivities both at the regional and the cellular levels when either one of these three anti-sera was used. Characterization of the immunoreactive peptides was achieved with molecular sieve filtration followed with Reverse Phase High Performance Liquid Chromatography of various rat tissues extracts. Identification was achieved by immunological analysis and chromatographic comparison with synthetic peptides. Immunoreactive materials corresponding to dermorphin, dermenkephalin and the spacer peptide were detected in either brain, stomach or intestine, indicating processing of the dermorphin precursor in these tissues. Immunoreactive species of higher Mr were also detected in all three tissues and may represent extended forms or homologous peptides. PMID- 2196879 TI - Insulin enhancer binding protein has helix-loop-helix structure. AB - Insulin gene expression is restricted to pancreatic B cells and the 5' flanking region is responsible for the tissue specificity. The GCCATCTG motif in this region of the rat insulin 1 gene functions as an enhancer for insulin transcription. A cDNA coding for a GCCATCTG motif-binding protein (IEBP1) was isolated from a rat pancreatic B cell tumor lambda gt11 library. The IEBP1 protein was found to be the rat counterpart of the immunoglobulin (Ig) enhancer binding protein E12/47 having a helix-loop-helix domain. This result indicates that the Ig gene and insulin gene employ the same (or a similar) binding protein as a part of their transcriptional apparatus. PMID- 2196881 TI - NMR studies of interactions of ligands with dihydrofolate reductase. AB - NMR spectroscopy is a useful technique for studying interactions, conformations and dynamic processes within ligand-protein complexes. Several examples of the application of the method to studies of complexes of anti-folate drugs with their target enzyme, dihydrofolate reductase, are discussed. PMID- 2196880 TI - Structural elements pertinent to the interaction of cyclosporin A with its specific receptor protein, cyclophilin. AB - Cyclophilin (163 amino acids; 17,737 daltons) is a ubiquitous cytosolic protein that specifically binds the potent immunosuppressive drug cyclosporin A (CsA). To characterize the structural details of this interaction, extensive use has been made of two-dimensional (2D) NMR methods. For studies on CsA, these methods are being used to assign the conformational space accessible to CsA by analysis of the spectra from the multiple CsA conformers present in slow exchange in mixed solvent systems. These same 2D NMR methods also have been used for extensive studies of the major bovine thymus cyclophilin (CyP) isoform and its complex with stoichiometric amounts of CsA. In the former case, these studies have revealed 81% of the 156 expected HN-H alpha crosspeaks. The complete spin-coupled spin systems for one-third of these amide resonances have been assigned according to amino acid type. After exhaustive D2O exchange, there remain 44 amide protons which exhibit 2D NMR features indicative of a hydrophobic domain with beta-sheet secondary structure. The CsA-complexed form of CyP exhibits a discrete structure and set of resonances in slow exchange with the drug-free CyP. The amino acids that have been specifically identified to be affected by the interaction are limited in number and include three Phe residues, the unique Trp at position 120, and two Ala residues. PMID- 2196882 TI - Computational methods for determining protein structures from NMR data. AB - The general procedures by which solution structures of proteins may be deduced from distance and angular constraints derived from NMR are reviewed, with an emphasis on practical aspects of the calculations. In addition, novel methods based on chemical shift calculations and on quantitative fits to nuclear Overhauser effect intensities are presented; these should provide improved understanding of the limits of our ability to simulate complex spectra, and may permit higher precision structures to be determined. PMID- 2196883 TI - NMR studies of the active site of DNA polymerase I and of a 50-residue peptide fragment of the enzyme. AB - Transferred nuclear Overhauser effects (NOEs) and selective T1 measurements were used to determine interproton distances in the substrates Mg2+dATP and Mg2+TTP bound to the large fragment of DNA polymerase I (Pol I). The distances are consistent with high anti, O1' endo conformations for the enzyme-bound substrates, similar to nucleotides of B-DNA. These substrate conformations show little or no change when the complementary RNA templates (rU)57 or (rA)50 are bound. In contrast, multiple conformations, including syn and anti species, are required to fit the interproton distances measured on the enzyme-bound guanine nucleotide substrates Mg2+dGTP and Mg2+ddGTP. These multiple substrate conformations simplify to a single high anti, O1' endo conformation when the complementary template (rC)37 is bound, possibly due to base-pairing with the template, as in the active complex. In the presence of both template and primer, enzyme-bound Mg2+ddGTP reverts to multiple conformations. This ability of Pol I to decrease the fraction of bound substrate which is appropriate for primer elongation may be an error-preventing mechanism. In all cases, the conformations of the average nucleotide of the enzyme-bound RNA templates are also B-like. Transferred NOEs from protons of the enzyme to those of bound dNTP substrates suggest hydrophobic (Ile, Leu) and an aromatic amino acid (Tyr) at the substrate binding site. Peptide I, a synthetic 50-residue peptide based on residues 728 to 777 of the Pol I sequence, containing the conserved sequence L-I-Y-G, retains significant secondary and tertiary structure in solution as found by circular dichroism (CD) and 2D NMR. While the X-ray structure shows 48% helix in this region, the sequence specific NOESY analysis suggests 18% helix, and the preservation of two of the three beta turns. Peptide I shows tight binding of dNTP substrates, the substrate analog 2',3'-trinitrophenyl-ATP, and duplex DNA, providing direct evidence that the active site for polymerization lies in this region of the enzyme, with the substrate binding along the O-helix near Leu-764, Ile-765, and Tyr-766. Another synthetic peptide, peptide II, based on residues 840 to 888 of the Pol I sequence also retains much secondary structure as detected by CD but does not bind the substrate analog TNP-ATP. PMID- 2196884 TI - Motional effects on NMR structural data. Comparison of spinach and Escherichia coli acyl carrier proteins. AB - Proteins in solution need not exist in a single rigid structure but can exist in a dynamic equilibrium among structural forms. The problems that this poses for structure determination using nuclear Overhauser effect data from two-dimensional NMR experiments are discussed and illustrated with data on functionally equivalent proteins from two different species. One of these proteins, acyl carrier protein from Escherichia coli, shows a single set of resonances, easily interpreted on the basis of a single rigid structure. However, the related protein, acyl carrier protein from spinach, shows two sets of resonances, suggesting that two conformers in dynamic equilibrium would be a better structural model. PMID- 2196885 TI - Measurement of cardiac output in pregnancy by Doppler technique. AB - Doppler technique of measuring cardiac output was evaluated during pregnancy. In a study of accuracy Doppler technique correlated well with thermodilution, (r = 0.95, y = 1.05x - 0.35). In a study of interoperator variability, the technique was found to be reproducible, (r = 0.92, y = 0.91x + 0.74). PMID- 2196887 TI - Microbiology of the lower genital tract and amniotic fluid in asymptomatic preterm patients with intact membranes and moderate to advanced degrees of cervical effacement and dilation. AB - The purpose of this prospective investigation was to evaluate the microbiology of the lower genital tract and amniotic fluid in asymptomatic women with preterm labor. We limited inclusion in the study to patients at 20 to 36 weeks' gestation whose membranes were intact and whose cervix was at least 50% effaced and 2 cm dilated. At the time of admission, we obtained an endocervical specimen for culture for Neisseria gonorrhoeae and for enzyme-linked immunoabsorbent assay for Chlamydia trachomatis and a vaginal specimen for culture for group B streptococci (GBS). We also performed transabdominal amniocentesis to collect amniotic fluid for Gram's stain, latex fixation test for GBS, and aerobic and anaerobic cultures. All patients received parenteral tocolytics. Women who had an immature lecithin to sphingomyelin ratio also received betamethasone. Only 1 of 72 women (1.4%, 95% confidence interval 0 to 4.1%) had a positive amniotic fluid culture. One patient (1.4%) had a positive Gram's stain, and two (2.8%) had positive latex fixation tests. None of these individuals subsequently had a positive culture. Eight women (11.1%) had positive tests for chlamydia, and four (5.5%) had positive vaginal cultures for GBS. None of the patients developed clinical evidence of chorioamnionitis, and only one had puerperal endometritis. None of the neonates had any complications due to infection. We conclude that, in our population, intra-amniotic infection is not a common cause of preterm labor in asymptomatic patients with intact membranes and that amniocentesis should not be performed routinely to assess the bacteriology of the amniotic fluid. PMID- 2196886 TI - Left ventricular stroke volume and output in healthy term infants. AB - Left ventricular output, left ventricular stroke volume, and systemic vascular resistance were measured noninvasively in 16 healthy term infants at 6 predefined time intervals from less than 15 minutes to 72 hours after birth. The blood flow velocity in the ascending aorta was measured by range-gated Doppler technique and multiplied by the cross-sectional area, measured by 2-dimensional and M-mode echocardiography to yield left ventricular output. Stroke volume was calculated by dividing left ventricular output by heart rate. Mean arterial blood pressure was measured by oscillometric technique and used for calculation of systemic vascular resistance. A poor association between heart rate and left ventricular output was found, whereas there was a very close relationship between stroke volume and left ventricular output. There was also a reciprocal relationship between systemic vascular resistance and stroke volume. This suggests that stroke volume and not heart rate is the main determinant of neonatal left ventricular output and that the low postnatal afterload might strengthen this relationship. PMID- 2196888 TI - Severe preeclampsia: is vasodilation therapy with hydralazine dangerous for the preterm fetus? AB - Increasing experimental and clinical evidence points to a subset of severe preeclamptic women who are hypovalemic with a low cardiac index and a high systemic vascular resistance, and in whom vasodilatory therapy may cause precipitate falls in maternal perfusion pressure, unless anticipated by prior correction of the hypovolemia. Since there is a paucity of adequately controlled clinical trials with appropriate definitions of hypotension or perinatal outcome, the consequences of such episodes for the preterm fetus are unknown. Epidemiologic evidence, using a logistic regression analysis model, is reviewed, which points to an association between a hypotensive episode following a commonly used drug, hydralazine, and a worse perinatal outcome in a study of severely hypertensive women delivered less than 32 weeks. An estimate of this risk, using the odds ratio, is 5.97 (95% confidence interval 1.84 to 19.35). PMID- 2196889 TI - Doppler assessment of fetal blood flow velocity waveforms during acute maternal oxygen administration as predictor of fetal outcome in post-term pregnancy. AB - The changes in fetal blood flow velocity waveforms during maternal administration of 60% humidified oxygen were assessed by Doppler ultrasonography in 45 post-term fetuses. During oxygen treatment, nine fetuses exhibited temporary increases (24.3 +/- 2.0% [1 standard deviation] above pretreatment values) in the pulsatility index at the level of internal carotid artery. Although no significant changes (2.9 +/- 5.1%) were found in the remaining 36 fetuses. In this former group a higher incidence of emergency cesarean delivery due to fetal distress and more neonatal complications were observed. Also, meconium staining of the amniotic fluid and low 1- and 5-minute Apgar scores occurred more frequently in the group of fetuses who responded to maternal oxygen administration. An increase of at least 20% in the pulsatility index of internal carotid artery during maternal hyperoxygenation may be a useful marker of adverse outcome in post-term fetuses. PMID- 2196890 TI - Review of endosseous implants for partially edentulous patients. AB - The scientific documentation of the biologic acceptability of the Branemark osseointegrated implant has increased the interest in implants. This documentation was done on completely edentulous patients and therefore is not necessarily transferable to partially edentulous patients. Demographic studies indicate an increased need for implant restoration, yet clinical documentation of the effectiveness of implants in the partially edentulous is not nearly as strong as for the completely edentulous patient. There is a great need for well-designed research to compare prosthodontic materials and techniques. This review summarizes the literature on implants in the partially dentate mouth. PMID- 2196891 TI - Implants in the treatment of the maxillofacial patient. AB - Despite the apparent advantages provided by implants to the maxillofacial patient, complete documentation of these benefits is lacking in the literature. This review uses existing published material as a basis to discuss the efficacy of implant use in maxillofacial prosthetics and the biologic rationale of the procedures. The use of implants with bone-anchored hearing aids; in maxillofacial surgery; and in maxillary, mandibular, and facial defects is presented. Reliable and valid patient-based evidence of treatment success, as suggested by the NIH Consensus Conference of 1988, is needed. PMID- 2196892 TI - Role of implants in the treatment of edentulous patients. AB - People wearing complete dentures need to develop considerable skills if they are to use their dentures successfully. A number of people are unable to master these skills and demand something better. The dental profession's attempts to satisfy this demand have taken a number of forms, but one consistent approach has been the attempt to produce dental implants that endure. This article reviews the literature relating to the use of implants in treating the edentulous patient, with emphasis being given to implants using the principle of osseointegration. These implants are used to support both fixed restorations and removable overdentures. Brief consideration is also given to the situation in which the quantity of available bone is insufficient to use implant fixtures. PMID- 2196893 TI - Influence of preparation site on the effectiveness of two dentine adhesives. AB - There are morphologic and chemical variations in dentine in different parts of a single tooth. The aim of this study was to ascertain whether the site of restoration cavities was related to marginal contraction gaps at the restoration/dentine interface. The results showed no significant relationship when using a commercially available dentine adhesive. However, when an experimental dentine adhesive was used, there was a significant difference in the size of the marginal contraction gaps on the buccal and lingual surfaces of restorations. PMID- 2196894 TI - Light-polymerized materials for custom impression trays. AB - Custom trays are indispensable for making impressions with elastomeric products. Previous studies have demonstrated that certain autopolymerized materials are particularly suitable, but had some limitations. The recently introduced halogen light-polymerized resins permit fabrication of custom trays that have the needed physical properties for accuracy and strength. No storage period is necessary for completion of polymerization, and the trays are not subject to distortion in moisture, making them suitable for use in the electroforming of casts. PMID- 2196896 TI - Complications, supplementary treatment, and maintenance in edentulous arches with implant-supported fixed prostheses. AB - The first 50 edentulous arches treated with osseointegrated fixed partial dentures at the Postgraduate Dental Education Center, Orebro, Sweden, were studied retrospectively with concern for complications and time used for supplementary treatment and maintenance. The longest observation period was 9 years, the shortest 3 years, and the mean 5.2 years. Twenty-two percent of the patients experienced fractures of artificial teeth and/or the acrylic resin superstructure. The most severe technical complications were fractured or bent abutment screws (three) and fracture of the framework (one). The average time for supplementary treatment and maintenance was as follows: for surgery, 0.16 hours per prosthesis and year; for prosthodontics, 0.64 hours per prosthesis and year; and for dental laboratory procedures, 1.0 hour per prosthesis and year. PMID- 2196895 TI - Chemical retention of composite resin to metal. AB - Three dental adhesives were used to chemically bond three dental veneering resins to a nickel-chromium alloy and a 52% gold alloy. As a control, all three veneering resins were applied directly to the aluminum-oxide-abraded surface without using an adhesive. The various combinations were subjected to a tensile load, and the tensile bond strength and failure location were recorded. The results indicated that the adhesives provided a statistically significant bond between the resin and the alloys. PMID- 2196897 TI - Tensile bond strengths of an electrolytically and chemically etched base metal. AB - This study compared the tensile bond strengths of a Ni-Cr-Be alloy electrolytically etched and chemically etched with three commercially available gels. Etched metal cylinders were bonded end-to-end with a resin luting agent and subsequently tested for tensile strength. Mean bond strengths and the character of bond failure were recorded. Significant differences were found between the electrolytically and chemically etched specimens. PMID- 2196898 TI - Review of attachments for removable partial denture design: 1. Classification and selection. AB - An attachment is a mechanical device, other than a clasp assembly, that functions as a direct retainer. Attachments for removable partial denture treatment are reviewed and a method for classifying different types of attachments is provided. Attachments are categorized as precision or semiprecision, depending upon the method of manufacture; internal or external, according to their intracoronal or extracoronal location relative to the abutment tooth; and rigid or resilient, as determined by the amount of movement allowed between the component parts. They are also classified by design. The advantages and disadvantages of attachment use as well as indications and contraindications are considered. Additionally, the conventional clasp-type direct retainer is compared to attachments. PMID- 2196899 TI - Ras genes may not always be targets of chemical carcinogen action. PMID- 2196900 TI - Mutational specificities of environmental carcinogens in the lacl gene of Escherichia coli. III: The cyclic nitrosamine N-nitrosopyrrolidine is a complex mutagen. AB - The mutational specificity of the cyclic nitrosamine N-nitrosopyrrolidine (NPYR) was determined through the DNA sequence characterization of 33 lacl-d mutations of Escherichia coli. Base substitution was the predominant class of mutation induced (91%). The majority of these (64%) occurred at GC base pairs, in accordance with the predicted significance of NPYR-derived guanine adducts. In addition, this nitrosamine efficiently produced other kinds of base substitution events as 11 of the 33 mutations occurred at AT base pairs. Deletion, frameshift, and duplication events were also recovered. The complexity of the NPYR mutational spectrum appears to be consistent with the suggestion that this compound acts through both direct and indirect mutational pathways. PMID- 2196901 TI - Plasma membrane-mediated nuclear uptake and chromatin binding of insulin in tumor cell lines. AB - Analysis of different cellular fractions after incubation of SW 948 and SW 707 colorectal carcinoma cells or WM 266-4 melanoma cells with 125I-insulin revealed the nondegraded hormone in the chromatin of these cells. Nuclear 125I-insulin was bound to specific fragments of EcoRI-, HaeIII-, and HincII-digested chromatin. A 45-kDa chromatin protein species that binds 125I-insulin was identified. Actinomycin D and cycloheximide inhibited the insulin-stimulated expression of chromatin receptors. Uptake of 125I-insulin by isolated nuclei occurred only in the presence of plasma membranes. Thus, at least some effects of insulin on target cells can be explained by direct gene regulation instead of "second messenger" action. PMID- 2196902 TI - Activation of c-Ki-ras not detectable in adenomas or adenocarcinomas arising in rat pancreas. AB - The objective of this study was to determine whether activation of c-Ki-ras occurs in carcinogen-induced rat pancreatic tumors. DNAs from 27 samples, which included adenomas, carcinomas in situ, and adenocarcinomas arising in azaserine treated rats and corn oil-gavaged rats along with a nafenopin-induced rat pancreatic adenocarcinoma were examined for mutation of c-Ki-ras at codons 12, 13, and 61 by using the polymerase chain reaction. Our results indicate that activation of c-Ki-ras is not a common event during pancreatic carcinogenesis in the rat. PMID- 2196903 TI - Expression and characterization of human CD4:immunoglobulin fusion proteins. AB - Different chimeric antibody-like molecules consisting of the four human CD4 extracellular domains (amino acids 1-369) fused to different parts of human IgG1 and IgM heavy-chain constant regions have been created and expressed in mammalian cells. For both IgG1 and IgM fusion proteins, the best expression in COS cells was observed for molecules lacking the CH1 domain of the heavy-chain constant region. The chimeric molecules are potent inhibitors of human immunodeficiency virus (HIV) infection and HIV-mediated cytotoxicity. A CD4:IgG1 hinge fusion protein, which was analyzed in more detail, binds efficiently to HIV gp160 and human Fc receptors and shows complement-assisted inhibition of viral propagation in culture. Half-life studies after intravenous application of the latter human fusion protein into mice and monkeys showed significant prolongation of serum survival compared to soluble CD4. An IgG2b murine homolog of the human CD4:IgG1 hinge fusion protein was prepared and evaluated in mice, where it was found to be nontoxic and to have no detectable effect on the humoral response to soluble antigen. PMID- 2196904 TI - Use of short oligonucleotides to screen cosmid libraries for clones containing G/C-rich sequences. AB - We have developed a method to identify clones containing recognition sequences for enzymes that cut mammalian genomes infrequently by direct screening of genomic libraries. The degenerate oligonucleotide NNGCGGCCGCNN, in which the internal 8 bases correspond to the recognition sequence of Not I, was used to screen a cosmid library, and it led to a greater than 10-fold enrichment in the number of clones containing Not I sites. This technique permits the efficient identification of sufficient clones from a chromosome-specific library to allow the construction of a complete pulsed-field map of that chromosome and to assist in finding genes in genomic DNA. PMID- 2196905 TI - Bibliography of the current world literature. PMID- 2196906 TI - Non-organic psychiatric and psychosocial syndromes associated with HIV-1 infection and disease. PMID- 2196907 TI - Parameters involved in the cell fusion induced by HIV. AB - Studies evaluating cell fusion by HIV indicate that optimal conditions for measuring this biological process involve the use of appropriate numbers of cells, the expression of HIV gp120 in infected cells, the presence of the CD4 protein on the surface of uninfected cells, and sugar moieties. Cellular metabolism and nucleic acid synthesis as measured by DNA, RNA and protein synthesis are not requires. Proteolytic enzymes eliminate virus fusion only when the uninfected cells involved in the process are treated. Since the CD4 protein remains on the surface of the treated cells, the structure of this receptor must be changed sufficiently so that it cannot participate in the fusion process. Alternatively, the results may indicate the elimination by trypsin of a specific fusion receptor. PMID- 2196908 TI - Detection of salivary immunoglobulin A antibodies to HIV-1 in infants and children. AB - Secretory immunoglobulin A (slgA) antibodies of non-maternal origin are present in newborns and slgA to HIV-1 antigens has been detected in infected adults. In this study we investigated the presence of HIV-1-specific IgA in saliva from 41 children (aged 1 day-46 months) born to women at risk for HIV-1 infection. Saliva samples were assayed for HIV-1 antibodies with IgA-specific Western blot. The samples from 10 out of 11 children with subsequently proven infection, including one aged 6 months, demonstrated IgA antibodies to HIV-1 envelope antigens. Samples from infants under 15 months, who were born to infected mothers and subsequently shown to be uninfected, were slgA negative. Of the 12 children with continued indeterminate HIV-1 status, eight showed neither slgA nor serologic evidence of infection and four showed slgA antibodies. HIV-1-specific slgA was detectable before the age of 15 months and may prove to be valuable in the diagnosis of HIV-1 infection in infants. PMID- 2196909 TI - Temporary increase in serum beta 2-microglobulin during treatment with interferon alpha for AIDS-associated Kaposi's sarcoma. AB - Beta 2-microglobulin (beta 2-M) levels were determined in the serum of 24 patients treated with high-dose human recombinant interferon-alpha (IFN alpha) for AIDS-associated Kaposi's sarcoma. There was a significant increase in serum beta 2-M levels, irrespective of the response to treatment. However, the increase of serum beta 2-M levels in responders appeared to be more pronounced than in those with progressive disease, but this difference was not significant. The increase was only found during the initial 8 weeks; thereafter, beta 2-M levels declined in patients with continuing clinical improvement during ongoing treatment with IFN alpha. This may have been related to IFN alpha dose modification at 8 weeks for all patients. The initial rise in serum beta 2-M might be related to the immunomodulation properties of IFN alpha. Because serum beta 2-M levels were also enhanced in non-responders, this rise does not demonstrate that immunomodulation by IFN alpha is a mechanism of anti-tumour activity in AIDS-associated Kaposi's sarcoma. PMID- 2196910 TI - [Absolute driving incapacity at 1.0 promille--an erroneous limit]. AB - Following a well known decision of the Bundesgerichtshof (BGH, German Federal Court) a driver with a blood alcohol concentration (BAC) of more than 0.13% is seen as "absolutely unfit for driving" and will be prosecuted by criminal law. This decision was based on the results of a comprehensive review of the literature about the effects of alcohol done 1966 by the Bundesgesundheitsamt (BGA, National Bureau of Health). There, severe impairments were described at levels above 0.1%, a value which the BGH "rounded up" to 0.11%. The possible errors of measurement were estimated as 0.02%. Adding both values yielded the legal limit of 0.13%. Most recently Salger (vice-president of the BGH) in a decisive manner pleaded for a reduction of this limit to 0.11% both by lowering the assumed measurement error to 0.01% and by taking back the rounding-up operation. Explicitely he based these intended corrections of the former decision on two arguments he derived from the scientific research on alcohol and driving: 1. Significant impairments are linked with BACs higher than 0.1%. 2. This was demonstrated by road-side studies, studies with instrumented cars, and driving simulators which are more valid methods to predict driving behavior than studies conducted in the laboratory. We proved these assumptions by analyzing the literature about driving studies as well as the literature from laboratory studies on alcohol. This article mainly concentrates on the empirical results coming from driving studies. It demonstrates a clear-cut empirical evidence that no single limit can be determined from where alcohol-induced impairment begins. Quality and quantity of this impairment strongly depends on how difficult the driving situation actually is. Therefore, BAC and situational difficulty act together in a synergistic way. A driver only confronted with standard traffic situations which are easy to handle may react correctly despite a BAC of 0.1% and quite more. If difficulty is slightly augmented to situations where a more controlled and/or precision-oriented non-automatic driving is required, significant impairments were seen at levels of 0.07%. In traffic situations with unpredictable events and/or extreme driving conditions severe impairments are found even at levels below 0.05%. These results perfectly match with the results from the laboratory studies. As a consequence, any public policy decision as to the acceptable legal limit of alcohol has to include a decision as to the difficulty of traffic situations which has to be mastered by the driver. Claiming that a normal driver has to deal efficiently with a medium level of difficulty the scientific evidence demands a legal limit of about 0.07%. PMID- 2196911 TI - Genetic aspects of ataxia-telangiectasia. AB - Ataxia-telangiectasia (A-T) is an autosomal recessive syndrome whose principal features are progressive cerebellar ataxia, oculocutaneous telangiectasia, varied immune defects, a high cancer incidence, and clinical and cellular sensitivity to ionizing radiation and certain radiomimetic compounds. Cell and chromosome complementation studies have provided some evidence that mutations leading to the A-T phenotype may have occurred at more than one locus. Mapping with DNA polymorphisms has localized the predominant A-T mutation to chromosome 11q22-23. Heterozygous carriers of an A-T allele constitute about 1% of the United States population and are at a high risk for certain cancers, most notably female breast cancer. Cloning of the A-T allele(s) will assist in the early or prenatal diagnosis of A-T and provide a firm basis for determining who, in the general population, carries this gene and is therefore at a high risk of cancer. PMID- 2196912 TI - Carbohydrates and fertilization in animals. AB - A frequently used mechanism for sperm-egg recognition in many species involves complementary protein-carbohydrate interaction. The usual paradigm includes complex glycoconjugates in reproductive tract fluids or on the eggs which are recognized by carbohydrate-binding proteins on the sperm surface. Various glycoconjugates are utilized in the steps of sperm capacitation, sperm binding to the egg extracellular matrix and vitelline membrane and induction of the acrosome reaction. Several types of complex glycoconjugates are involved in these processes, including proteoglycans, lactosaminoglycans, sulfated fucose containing glycoconjugates, and glycoproteins. There appear to be some structural similarities between active glycoconjugates; they are large in molecular weight and complex, and they are often sulfated, fucosylated, and attached to a protein through serine or threonine residues. In some species, the protein core of the glycoconjugates also participates in the interaction by limiting the binding of carbohydrates to sperm only of the relevant species, likely by providing the proper steric arrangement for the interaction. In other cases the protein core seems to serve more as a crosslinker of the carbohydrate moieties. This review discusses the types of glycoconjugates implicated in fertilization and the complementary lectin-like proteins found on sperm. PMID- 2196914 TI - [Replication characteristics of plasmids and their dependence of recA gene for the initiation of Escherichia coli chromosome replication in the integrated state]. AB - E. coli dnaA46 fails to grow and form colonies at 40 degrees C; integrated with plasmid enables it to grow at 40 degrees C or 42 degrees C. In a previous paper we reported that the replication of chromosome initiated by the integrated F' plasmid was recA gene dependent. In this paper we report further the behavior of 5 plasmids and 2 phages as to their dependence of recA gene in the integrated state. It was demonstrated that the dependence or independence of recA gene is not related to the direction of replication of the plasmids or phages in the free state. The hypothesis that the function of recA gene is to convert the unidirectionally replicating machinery in the free state to the bidirectionally replicating one in the integrated state is refuted accordingly. PMID- 2196913 TI - [The selective isolation of cosmid clones by homologous recombination in Escherichia coli--a cosmid clone containing t complex linkage DNA sequence of mouse was isolated]. AB - A procedure for the selective isolation of specific cosmid clones by homologous recombination between cosmid clones of genomic library and a probe DNA sequence cloned in a plasmid in vivo has been developed. The cosmid library was constructed in a rec- host cell strain and packaged into phage particles in vivo. The rec+ host cells containing a DNA sequence used as selection probe cloned in the pUC plasmid were infected by packaged cosmid phage particles. There is no homology between cosmid and the plasmid vectors. After a period of 1-3 hr. for the recombination to take place, the probe plasmids were integrated into cosmid, in which the DNA sequence are homologous with the probe, by homologous recombination. The cosmids are then packaged in vivo and transferred into a rec- cell strain. The specific cosmid clones were selected by double antibiotic resistance carried by both vectors. The probe plasmid can be excised by lambda excision enzyme by using superinfection with red+ phage. After packaging in vivo, these cosmid revertants can be identified on Xgal plate. A cosmid clone containing the t complex linkage DNA sequence of mouse was selected by using the procedure above with a probe derived from microdissected metaphase chromosome. PMID- 2196915 TI - Factors affecting the Gates' measurement of glomerular filtration rate. AB - The following technical factors affect the Gates' measurement of glomerular filtration rate (GFR): 1) net injected activity, 2) kidney depth, 3) corrected kidney counts. In the syringe measurement prior to injection, self-attenuation causes 16% data loss for a volume of 0.5 ml if the syringe is positioned perpendicular to the collimator face. A +/- 1 cm error in true kidney depth may cause a 16% difference in GFR in an adult. The choice of the background region of interest (ROI), for background subtraction significantly affects the calculation. To minimize errors in the Gates' estimate of GFR we recommend 1) that syringe counting be done with the syringe parallel to the collimator face; 2) that the i.v. set be included in the postsyringe measurement; in cases of extravasation, the injection site should also be counted; 3) that kidney depth, especially for ectopic and transplanted kidneys be estimated by ultrasound or using lateral views; and 4) that a background ROI for each kidney be used. PMID- 2196916 TI - Radionuclide imaging in osteitis deformans. AB - New knowledge of osteoclastic function and new treatments to reduce osteolytic activity have combined to yield new degrees of biochemical control over the increased rate of bone resorption and formation that characterized osteitis deformans (OD; Paget's disease). We have briefly outlined current concepts, and provided an example of the role radionuclide imaging can play in delineating the skeletal areas involved in this disease. PMID- 2196918 TI - [Individual selection of programs for single-chamber electrocardiostimulators]. PMID- 2196917 TI - Exocytosis: the role of Ca2+, GTP and ATP as regulators and modulators in the rat mast cell model. AB - Cells and tissues release preformed materials contained in secretory granules into the extracellular environment by the mechanism of exocytosis which involves selective fusion of perigranular membranes with the plasma membrane. While the mechanism is believed to be shared between all cells that undergo exocytotic secretion, the molecular details of the interaction between the two fusing membranes are far from being understood. Recent advances have been based on the technique of membrane permeabilization which allows the composition of the cytosol to be precisely controlled. A role for a previously unsuspected GTP binding protein (GE) in the regulation of the terminal steps of exocytosis has thereby been revealed. Among mammalian secretory cells, the mast cell has proved to be particularly amenable for investigations in this area. PMID- 2196919 TI - Histologic changes in the mouse epididymis fixed in the abdominal cavity. AB - Histologic changes in the mouse epididymides were examined by light and electron microscopy 1, 3, 6 and 10 weeks after surgical fixation of the testes and epididymides to the internal abdominal wall at 2 months of age. In the epididymides subjected to the cryptorchid surgery, the principal cells in the segment next to the initial segment became taller, the nuclei were translocated to a higher position, and the widened infranuclear cytoplasm turned pale. The supranuclear cytoplasm showed a decrease in PAS stainability. Electron microscopy revealed that the infranuclear cytoplasm, which is occupied by small vesicular endoplasmic reticulum in the normal cells, was filled with distended rough endoplasmic reticulum. These changes first appeared one week after operation, further developing with time. Similar changes were observed when the epididymis was in the abdominal position with the testis in the scrotal position, or with the efferent duct ligated to block the testicular fluid flow into the epididymis. It is suggested that the epididymal changes recorded in this paper are induced by the elevation of temperature caused by the translocation from the scrotum to the abdomen. PMID- 2196920 TI - Management of the unerupted maxillary canine. AB - In orthodontic practice, many patients present with unerupted and impacted maxillary canine teeth. The clinical outcome is frequently compromised by a failure to diagnose the problem at the appropriate age. This article reviews the development of the maxillary canine, the assessment of normal and abnormal eruptive paths and the options for treatment, with particular emphasis on interceptive measures. PMID- 2196921 TI - Roentgen stereophotogrammetric analysis. AB - Soon after Roentgen's discovery, the 'new' rays were used to produce stereoscopic images or used for spatial reconstruction of positions of foreign bodies. However, no systematic use of roentgen stereo measurements seems to have occurred until the 1970's, although many attempts have been made before. Since 1972, a system for roentgen stereophotogrammetry has been in use at the University Hospital in Lund. The system has been named RSA, roentgen stereophotogrammetric analysis. It is a complete system, including instrumentation for implanting tantalum landmarks, devices for calibration of the stereo roentgen set-up, and comprehensive software. Using different calibration set-ups, any part of the body can be investigated under different conditions using standard roentgen equipment. The computer programs make it possible to calculate spatial landmark coordinates from measured film coordinates, and further to calculate growth, and volume changes or kinematic variables in well-defined and generally used terms. After the basic principles have been established, a survey of applications grouped according to anatomic regions follows. Special emphasis is laid on total hip and knee replacement, which besides complex craniofacial and spinal disorders, are the most rewarding fields of study. PMID- 2196923 TI - Ultrasonically guided percutaneous drainage of breast abscesses. AB - Four patients with breast abscesses developed during lactation were successfully treated by ultrasonically guided percutaneous drainage under local anaesthesia. Three patients continued nursing during and after the period of treatment and 2 patients were treated as out-patients. The cosmetic results were excellent. No recurrence of abscess was observed following the treatment. Ultrasonically guided percutaneous drainage as an alternative to surgery is discussed. PMID- 2196922 TI - Ultrasonography of jumper's knee. AB - The aim of the study was to evaluate the role of ultrasonography (US) in the management of jumper's knees. Sixty-two cases of clinically suggested jumper's knees, 52 asymptomatic contralateral knees and 100 asymptomatic knees of healthy middle aged men were examined. In the symptomatic group US was normal in 25 cases, all recovered with conservative therapy. In 31 symptomatic knees the findings were consistent with jumper's knee as a hypoechoic lesion located in the upper insertion of the patellar tendon in 23 cases and in the distal insertion in one case. In 7 cases the lesion was situated in the insertion of the quadriceps tendon. Surgery was performed on 20 knees and in all of them there was a lesion matching the lesion detected by US. In 6 cases US findings were pathologic, but different from jumper's knee. US findings consistent with jumper's knee could not be detected in the asymptomatic group. PMID- 2196924 TI - Pharmacological elimination of tumor cells contaminating normal human bone marrow using PTT-119. AB - In this study, we evaluated the inhibitory effects of PTT-119, a new tripeptide which is known to be a bifunctional alkylating agent, on two tumor cell lines with different origins: SK-DHL-2 (B-cell diffuse histiocytic lymphoma cell line) and RPMI 8226 (Multiple myeloma patient cell line) and compared the toxicity of PTT-119 toward normal human bone marrow granulocyte macrophage (CFU-GM), erythroid (BFU-E), and pluripotent (CFU-GEM) progenitors. Reduction of at least four logs was achieved on clonogenic myeloma cells after 1 hr of treatment with 25 micrograms/mL of PTT-119 either in the presence or absence of irradiated bone marrow (BM) cells. More than three and at least four logs of lymphoma cell kill were found after 1 hr of incubation with 25 and 40 micrograms/mL of the tripeptide, respectively. PTT-119 antitumor effects on SK-DHL-2 were only slightly affected in the presence of an excess of BM cells. BM cells treated for 1 hr with 25 micrograms/mL of PTT-119 showed a mean recovery of 4.5, 3.8, and 13.8% of CFU-GM, BFU-E, and CFU-GEM, respectively. The addition of 5- and 10-fold excesses of red blood cells (RBC) produced a slightly higher recovery of these hematopoietic progenitors. These results suggest that PTT-119 may be useful as a chemotherapeutic agent for the ex vivo treatment of bone marrow grafts. PMID- 2196925 TI - Therapeutic focus. Management of insomnia. PMID- 2196926 TI - Problems with clinical trials in general practice--a double-blind comparison of cream containing miconazole and hydrocortisone with hydrocortisone alone in the treatment of intertrigo. AB - A double-blind comparative study between 1% hydrocortisone cream and a combination of 1% hydrocortisone cream and 2% miconazole cream has highlighted some of the problems with this type of research in general practice. The collection of adequate patient numbers within a predefined time scale proved a major problem. However, the study demonstrated the safety and efficacy of both these preparations in the treatment of intertrigo. PMID- 2196927 TI - Effect of 1% mandelic acid as a bladder irrigation fluid in patients with in dwelling catheters. AB - The effect of 1% mandelic acid bladder washouts on 40 patients who were using in dwelling catheters was studied. The procedure appeared to benefit those colonised with Pseudomonas species but not those colonised with Proteus species. The subject of bladder irrigation is briefly reviewed. PMID- 2196928 TI - Similar effects on murine haemopoietic compartment of low dose rate single dose and high dose rate fractionated total body irradiation. Preliminary results after a unique dose of 750 cGy. AB - This study was designed to compare two different modalities of TBI which are currently used in clinical practice. The same dose of 750 cGy was given to CBA mice either in a single dose at a low dose rate (4 cGy min-1) (STBI) or in a fractionated regimen (six fractions of 125 cGy three times a day) at a higher dose rate (25 cGy min-1) (FTBI). After TBI completion we simultaneously studied the in vivo radiation response of bone marrow cells, two murine bone marrow clonogenic cells (CFU-S and GM-CFC) and peripheral blood lymphocytes and granulocytes for a period of 1 month. The percentage of spleen erythrocytic and granulocytic colonies was also determined. No significant differences were observed between the two groups in the first 48 hours after irradiation except in bone marrow cell numbers, probably due to differences in the overall treatment time between the two TBI schedules. After the first 48 hours the repopulation patterns of the different cells were very similar in both groups. These findings suggest that the different dose rates and fractionation used in this study caused similar radiation damage to the murine haemopoietic system. Moreover, no significant repopulation occurred during the longer overall treatment time of the fractionated regimen. These preliminary results must be corroborated with a larger range of doses before any firm conclusion can be drawn. PMID- 2196929 TI - Gene therapy: current status and future directions. PMID- 2196930 TI - Vitamin K and vitamin K-dependent proteins. PMID- 2196931 TI - The effects of rhGM-CSF on the neutrophil respiratory burst when studied in whole blood. AB - A simple semiquantitative cytofluorometric method has been developed for measuring neutrophil respiratory burst activity in whole blood samples. This technique avoids the introduction of laboratory artefacts which modulate neutrophil function. In addition, flow cytometric analysis allows the response to be studied in individual cells. We show here that neutrophils examined freshly ex vivo, exhibit only weak respiratory burst activity in response to stimulation with the chemotactic peptide FMLP (10(-6) M). Prior incubation with rhGM-CSF results in an increase in the number of responding cells from 13.5 +/- 2.36% (mean +/- SEM) to 46.7 +/- 6.3% (P less than 0.0001) with an increase in total respiratory burst activity of 567% (P = 0.001). The majority of neutrophils in whole blood (67.1 +/- 8.1%) exhibit respiratory burst activity in response to stimulation with phorbol ester (1 micrograms/ml of TPA), and this response is also significantly primed by rhGM-CSF (P = 0.004). The enhancement of respiratory burst activity induced by rhGM-CSF is due to both recruitment of previously unresponsive neutrophils, and to intensification of the response of the responding cells. In vivo administration of rhGM-CSF also results in priming of the respiratory burst in response to FMLP, although the enhancement of activity is not as great as that obtained when pre-infusion blood samples are incubated with rhGM-CSF in vitro. PMID- 2196932 TI - Frequencies of Band 3 variants of human red cell membranes in some different populations. AB - A variant of Band 3, the major protein of the erythrocyte membrane, was observed by Mueller and Morrison in 1977 in 6-7% of healthy blood donors on sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of erythrocyte membranes treated with pronase. Pronase treated red cells containing this first recognized variant [here designated 'Band 3-Memphis (m)'] section had two bands of about 63,000 and 60,000 Mr while pronase treated normal cells had only the lighter Mr band. The present study includes data on the frequency of variants resembling Band 3-Memphis in patients of different ethnic groups and on random donors obtained earlier in Memphis. These variants were detected by the original method of Mueller and Morrison and were not associated with recognized clinical or haematological abnormalities. Significantly higher gene frequencies for the variants of the (m) type were observed in American Indians, African Americans and Filipinos than in Caucasians; putative heterozygotes and homozygotes were identified among each of these groups. The frequency of silent Band 3 polymorphisms in different populations should be considered in the interpretation of clinical findings associated with the presence of Band 3 variants. PMID- 2196933 TI - Adjuvant immunotherapy with BCG of acute myeloid leukemia: a 15-year follow-up. PMID- 2196934 TI - Preventing IUCD-related pelvic infection: the efficacy of prophylactic doxycycline at insertion. AB - Most of the small increased risk in pelvic inflammatory disease (PID) associated with the intrauterine contraceptive device (IUCD) appears to be caused by bacterial contamination of the endometrial cavity at the time of insertion. This randomized clinical trial of 1813 women in Nairobi, Kenya, assessed the effectiveness of 200 mg of doxycycline given orally at the time of insertion in reducing the occurrence of PID. The rate of this infection in the doxycycline treated group was 31% lower than that in the placebo-treated group (1.3 and 1.9%, respectively; RR 0.69; 95% CI 0.32 to 1.5). The rate of an unplanned IUCD-related visit to the clinic was also 31% lower in the doxycycline-treated group (RR 0.69; 95% CI 0.52 to 0.91). Although the significance level (P = 0.17) for the reduction is PID does not meet the conventional standard of 0.05, the results may be suggestive of an effect. Moreover, the reduction in IUCD-related visits (P = 0.004) not only represents an important decrease in morbidity but also substantiates the reduction found for PID. Further studies are needed to corroborate these results. Consideration should be given to the prophylactic use of doxycycline at the time of IUCD insertion as an approach to preventing PID and other IUCD-related morbidity. PMID- 2196935 TI - Alterations in bladder volume and the ultrasound appearance of the cervix. PMID- 2196936 TI - Planned trial of transcervical resection of the endometrium versus hysterectomy. PMID- 2196937 TI - Saccharomyces cerevisiae phosphoenolpyruvate carboxykinase: physicochemical characteristics of the nucleotide binding site, as deduced from fluorescent spectroscopy measurements. AB - Saccharomyces cerevisiae phosphoenolpyruvate carboxykinase [ATP:oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.49] is inactivated by the fluorescent sulfhydryl reagent N-(iodoacetyl-N'-(5-sulfo-1 naphthyl)ethylenediamine (1,5-IAEDANS). The inactivation reaction follows pseudo first-order kinetics with respect to active enzyme to less than 10% remaining enzyme activity, with a second-order inactivation rate constant of 2.6 min-1 mM-1 at pH 7.5 and 30 degrees C. A stoichiometry of 1.05 mol of reagent incorporated per mole of enzyme subunit was found for the completely inactivated enzyme. Almost complete protection of the enzyme activity and of dansyl label incorporation are afforded by MnADP or MnATP, thus suggesting that 1,5-IAEDANS interacts with an enzyme sulfhydryl group at the nucleotide binding site. The fluorescence decay of the AEDANS attached to the protein shows a single exponential behavior with a lifetime of 18 ns. A comparison of the fluorescence band position and the fluorescence decay with those of the adduct AEDANS acetylcysteine indicates a reduced polarity for the microenvironment of the substrate binding site. The quenching of the AEDANS moiety in the protein can be described in terms of a collisional and a static component. The rate constant for the collisional component is much lower than that obtained for the adduct in a medium of reduced polarity. These last results indicate that the AEDANS moiety is considerably shielded from the solvent when it is covalently attached to PEPCK. PMID- 2196938 TI - Insulin binding to its receptor induces a conformational change in the receptor C terminus. AB - Antibodies against peptides corresponding to sequences in the C-terminus of the insulin receptor beta-subunit were used to approach the putative role of this receptor domain in signal generation. Two sequences were chosen and correspond to peptide C1, comprising amino acids 1309-1326, and peptide C2, comprising amino acids 1294-1317. The two antibodies produced distinct immunoprecipitation patterns as a function of the insulin receptor form and recognized changes in the insulin receptor molecule induced by ligand binding and autophosphorylation. Both antipeptides, anti-C1 and anti-C2, showed an important decrease in their recognition capacity for the receptor occupied by insulin when compared to the empty receptor. Further, anti-C1 had a lower affinity for the phosphorylated receptor compared to the unphosphorylated receptor and failed to recognize a fraction of the phosphoreceptor population. In contrast, anti-C2 had similar affinities for the phosphorylated and unphosphorylated receptors but was unable to interact with part of the unphosphorylated receptors. Finally, using immunoblotting of the receptor to analyze the denatured molecules, we showed that the phosphorylation-induced changes detected by anti-C1 are retained, suggesting that they are likely not of a conformational nature. In contrast, the insulin induced changes in the receptor molecule disappear with receptor denaturation which points to their reversible nature. We conclude from these data that (i) antipeptides against the receptor C-terminal sequence are able to distinguish between phosphorylated and unphosphorylated receptor forms and (ii) binding of insulin to its receptor leads to a reversible, phosphorylation-independent, and possibly conformational change at the level of the receptor C-terminal domain. PMID- 2196939 TI - Electrostatic control of charge separation in bacterial photosynthesis. AB - Electrostatic interaction energies of the electron carriers with their surroundings in a photosynthetic bacterial reaction center are calculated. The calculations are based on the detailed crystal structure of reaction centers from Rhodopseu-domonas viridis, and use an iterative, self-consistent procedure to evaluate the effects of induced dipoles in the protein and the surrounding membrane. To obtain the free energies of radical-pair states, the calculated electrostatic interaction energies are combined with the experimentally measured midpoint redox potentials of the electron carriers and of bacteriochlorophyll (BChl) and bacteriopheophytin (BPh) in vitro. The P+HL- radical-pair, in which an electron has moved from the primary electron donor (P) to a BPh on the 'L' side of the reaction center (HL), is found to lie approx. 2.0 kcal/mol below the lowest excited singlet state (P*), when the radical-pair is formed in the static crystallographic structure. The reorganization energy for the subsequent relaxation of P+HL- is calculated to be 5.0 kcal/mol, so that the relaxed radical pair lies about 7 kcal/mol below P*. The unrelaxed P+BL- radical-pair, in which the electron acceptor is the accessory BChl located between P and HL, appears to be essentially isoenergetic with P*.P+BM-, in which an electron moves to the BChl on the 'M' side, is calculated to lie about 5.5 kcal/mol above P*. These results have an estimated error range of +/- 2.5 kcal/mol. They are shown to be relatively insensitive to various details of the model, including the charge distribution in P+, the atomic charges used for the amino acid residues, the boundaries of the structural region that is considered microscopically and the treatments of the histidyl ligands of P and of potentially ionizable amino acids. The calculated free energies are consistent with rapid electron transfer from P* to HL by way of BL, and with a much slower electron transfer to the pigments on the M side. Tyrosine M208 appears to play a particularly important role in lowering the energy of P+BL-. Electrostatic interactions with the protein favor localization of the positive charge of P+ on PM, one of the two BChl molecules that make up the electron donor. PMID- 2196940 TI - [The methodological problems of the correlation of biochemistry and physiology in current research]. AB - An attempt to treat critically the key methodological positions of modern biochemistry, primarily, the medical biochemistry with reference to the physiologic, pathophysiologic and clinical tasks is made. The author puts forward questions: 1) if it is possible to apply traditional approaches (principles) of biochemical investigation developed on purified systems to the whole organism systems in situ and etc.; 2) if it coincides the methodical approaches of biochemistry on the one hand and physiology (pathophysiology)--on the other one, considering the mechanisms of disease development and correspondingly the assessment and choice of therapeutic methods; 3) if there exists a necessity to create a unite methodology of biochemical and physiologic knowledge as a basis of modern medical science as a whole. Some examples showing the possible ways of new methodic consideration of traditional conceptions of in vitro biochemistry are given. PMID- 2196942 TI - Cytometric and histopathologic features of tumors detected in a randomized mammography screening program: correlation and relative prognostic influence. AB - Cytometric determination of S-phase fraction and ploidy type was performed on 430 tumors detected within a randomized trial of mammographic screening. The results were compared to several histopathologic features. A high S-phase fraction was estimated in tumors with a high grade of malignancy and other histopathologic findings related to rapid tumor progression, including lack of tubule formation, a high mitotic index, marked nuclear pleomorphism, multifocal cancer growth, tumor emboli in lymphatic and blood vessels, tumor necrosis, and inflammatory reaction. DNA aneuploidy was correlated with a high malignancy grade, frequent mitoses, a high degree of nuclear pleomorphism, vascular invasion, necrosis, and the presence of noninvasive ductal carcinoma. Both cytometric variables were inversely related to the degree of elastosis. Positive nodes, large tumor size, DNA aneuploidy, a high S-phase fraction, high grade of malignancy, lack of tubule formation, as well as high mitotic index and pleomorphism, presence of multifocal cancer, and vascular invasion, predicted a significantly shorter distant recurrence-free interval after a median follow-up time of 46.6 months. Elastosis and the presence of estrogen and progesterone receptors indicated favorable prognosis. In the multivariate analysis, only lymph node status, tumor size, S phase fraction, and multifocal growth pattern had independent prognostic value. PMID- 2196943 TI - Legal duties of psychiatric patients. AB - Psychiatric practice involves an implied contract in which each party fulfills a specialized role and incurs corresponding duties and obligations to be discharged as best able. Patients incur duties at three levels. First are specific duties that arise from patients' specialized role in their own health care: (1) to provide accurate and complete information, and (2) to cooperate with treatment within the bounds of informed consent. Second are general duties that apply to all citizens, but are especially relevant within the mental health context: (1) to respect the physical integrity of self, others, and property, and (2) to obey the law. The controversial "duty to protect" is at a third level, a transcendent duty that is specific to the context at hand, but in principle can apply to more than one party. Advantages of enforcing patients' duties include better care by treating professionals, optimum level of functioning of patients, and improved systems-wide morale and safety. Breach of patients' duty has many potential consequences in the forensic sphere: termination of care, malpractice defense, criminal prosecution, and tort liability. Complicating factors include the degree and effect of patients' psychiatric impairment, patients' legal status, and the role played by psychotherapeutic transference. PMID- 2196941 TI - Long-term adjuvant tamoxifen therapy for breast cancer. AB - Tamoxifen (ICI46,474) is a competitive inhibitor of estrogen action which has found ubiquitous application in the treatment of breast cancer. The drug is the front line endocrine therapy for breast cancer and is the proven treatment of choice for the adjuvant therapy of postmenopausal women with node-positive disease. Tamoxifen is available for the treatment of premenopausal patients with advanced disease, and is being evaluated in clinical trials as an adjuvant therapy for premenopausal patients with either node-positive or node-negative disease. Laboratory studies demonstrate that tamoxifen is a tumoristatic agent and long-term treatment strategies (chemosuppression) should be considered to apply the antiestrogen to its maximal therapeutic advantage. Optimal therapy with tamoxifen may also be achieved by treatment strategies to lower circulating estrogen levels in the premenopausal patient. Tamoxifen is a well tolerated drug, and long-term therapy does not appear to induce metabolic tolerance. Concerns about premature osteoporosis or cardiovascular disease appear to be unfounded because tamoxifen has an appropriate level of target site-directed estrogenic activity. Isolated reports about the growth or appearance of endometrial carcinoma during long-term adjuvant tamoxifen therapy must be balanced against the risks of withholding treatment to patients with a fatal disease. PMID- 2196945 TI - Cervical cytology. PMID- 2196944 TI - Graves' ophthalmopathy. PMID- 2196947 TI - Experiences of a battalion medical officer in the retreat to Dunkirk: IV. PMID- 2196946 TI - Relaxation therapy and continuous ambulatory blood pressure in mild hypertension: a controlled study. AB - OBJECTIVE: To determine the long term effects of relaxation therapy on 24 hour ambulatory intra-arterial blood pressure in patients with mild untreated and uncomplicated hypertension. DESIGN: Four week screening period followed by randomisation to receive either relaxation therapy or non-specific counselling for one year. Ambulatory intra-arterial blood pressure was measured before and after treatment. SETTING: Outpatient clinic in Amsterdam's university hospital. SUBJECTS: 35 Subjects aged 20-60 who were being treated by general practitioners for hypertension but were referred to take part in the study. At three consecutive screening visits all subjects had a diastolic blood pressure without treatment of 95-110 mm Hg. Subjects were excluded if they had damaged target organs, secondary hypertension, diabetes mellitus, a cholesterol concentration greater than 8 mmol/l, or a history of malignant hypertension. INTERVENTIONS: The group allocated to relaxation therapy was trained for eight weeks (one hour a week) in muscle relaxation, yoga exercises, and stress management and continued exercising twice daily for one year with monthly visits to the clinic. The control group had the same attendance schedule but had no training and were requested just to sit and relax twice a day. All subjects were asked not to change their diet or physical activity. MAIN OUTCOME MEASURE: Changes in ambulatory intra-arterial blood pressure after one year of relaxation therapy or non-specific counselling. RESULTS: Mean urinary sodium excretion, serum concentration of cholesterol, and body weight did not change in either group. Diastolic pressures measured by sphygmomanometry were 2 and 3 mm Hg lower in subjects in the relaxation group and control group respectively at the one year follow up compared with initial readings. The mean diastolic ambulatory intra arterial pressure during the daytime had not changed after one year in either group, but small treatment effects could not be excluded: the mean change for the relaxation group was -1 mm Hg (95% confidence interval -6 to 3.9 mm Hg) and for the control group -0.4 mm Hg (-5.3 to 4.6 mm Hg). Mean ambulatory pressure in the evening also had not changed over the year, and in both groups nighttime pressure was 5 mm Hg higher. The variability in blood pressure was the same at both measurements. CONCLUSIONS: Relaxation therapy was an ineffective method of lowering 24 hour blood pressure, being no more beneficial than non-specific advice, support, and reassurance--themselves ineffective as a treatment for hypertension. PMID- 2196948 TI - Management of urinary tract infection and vesicoureteric reflux in children. 1. Operative treatment has no advantage over medical management. PMID- 2196949 TI - Management of urinary tract infection and vesicoureteric reflux in children. 2. The case for surgery. PMID- 2196950 TI - Infectious disease control. PMID- 2196951 TI - ABC of major trauma. Head injuries--I. PMID- 2196952 TI - Intrauterine growth retardation and umbilical artery flow. PMID- 2196953 TI - Management of menorrhagia. PMID- 2196954 TI - A randomised controlled trial of surgery for glue ear. AB - OBJECTIVE: To assess the effect of five different surgical treatments for glue ear (secretory otitis media) on improvement in hearing and, assuming one or more treatments to be effective, to identify the appropriate indications for surgery. DESIGN: Randomised controlled trial of children receiving (a) adenoidectomy, bilateral myringotomy, and insertion of a unilateral grommet; (b) adenoidectomy, unilateral myringotomy, and insertion of a unilateral grommet; (c) bilateral myringotomy and insertion of a unilateral grommet; and (d) unilateral myringotomy and insertion of a grommet. Children were followed up at seven weeks, six months, 12 months, and 24 months by symptom history and clinical investigations. SETTING: Otolaryngology department in an urban hospital. PATIENTS: 149 Children aged 4-9 years who were admitted for surgery for glue ear and who had no history of previous operations on tonsils, adenoids, or ears and no evidence of sensorineural deafness. Inadequate follow up information on levels of hearing and on middle ear function was obtained from 22. MAIN OUTCOME MEASURES: Mean hearing loss (dB) of the three worst heard frequencies between 250 and 4000 Hz, results of impedance tympanometry, and parental views on their child's progress. RESULTS: In the 127 children for whom adequate information was available ears in which a grommet had been inserted performed better in the short term (for at least six months) than those in which no grommet had been inserted, irrespective of any accompanying procedure. Most of the benefit had disappeared by 12 months. Adenoidectomy produced a slight improvement that was not significant, though was sustained for at least two years. The ears of children who had had an adenoidectomy with myringotomy and grommet insertion, however, continued to improve so that two years after surgery about 50% had abnormal tympanometry compared with 83% of those who had had only myringotomy and grommet insertion, and 93% of the group that had had no treatment. Logistic regression analyses identified preoperative hearing level as the single best predictor of good outcome from surgery. Other variables contributed little additional predictive power. CONCLUSIONS: If the principal objective of surgery for glue ear is to restore hearing then our study shows that insertion of grommets is the treatment of choice. The addition of an adenoidectomy will increase the likelihood of restoration of normal function of the middle ear but will not improve hearing. When deciding appropriate indications for surgery, a balance has to be made between performing unnecessary operations and failing to treat patients who might benefit from surgical intervention. Preoperative audiometry scores might be the best predictor in helping to make this decision. PMID- 2196955 TI - A simple method to detect Helicobacter pylori in gastric specimens. PMID- 2196956 TI - ABC of major trauma. Head injuries--II. PMID- 2196957 TI - Psychological treatment for depressive disorder. PMID- 2196958 TI - Audit of amniocentesis. PMID- 2196959 TI - Late onset asthma. PMID- 2196960 TI - Antireflux surgery. PMID- 2196961 TI - "It isn't epilepsy is it, doctor?". PMID- 2196962 TI - Randomised double blind trial of single dose doxycycline for treating cholera in adults. AB - OBJECTIVE: To compare the efficacy of a single dose of doxycycline (200 or 300 mg) with the standard multiple doses of tetracycline in patients with cholera. DESIGN: Randomised double blind controlled trial. Patients were given a single 200 mg dose of doxycycline, a single 300 mg dose of doxycycline, or multiple doses of tetracycline (500 mg, six hourly intervals). SETTING: Hospital in Bangladesh treating diarrhoea. PATIENTS: 261 Patients aged over 15 admitted to the hospital with severe dehydration due to acute watery diarrhoea associated with Vibrio cholerae. All vibrios isolated from the stools and rectal swabs of patients, including those patients with prolonged excretion of vibrios, were sensitive to tetracycline. The stools of all patients at admission were negative for shigella and salmonella. INTERVENTIONS: All patients received rapid intravenous acetate solution for the first four hours after admission to hospital. They were then entered in the study and randomised. Oral rehydration was started immediately after the intravenous treatment. If signs of severe dehydration reappeared during oral treatment patients were given rapid intravenous acetate solution until dehydration was fully corrected. MAIN OUTCOME MEASURES: Stool output in first 24 hours and till diarrhoea stopped, total intake of oral rehydration fluid, duration of diarrhoea, and excretion of vibrio after receiving antibiotic treatment. RESULTS: The median stool outputs during the first 24 hours (275 ml/kg body weight) and till diarrhoea stopped (296 ml/kg body weight) were significantly higher in patients receiving 200 mg doxycycline as a single dose than in patients receiving either standard tetracycline (242 ml/kg body weight and 254 ml/kg body weight) or 300 mg doxycycline (226 ml/kg body weight and 255 ml/kg body weight). Similarly, median consumption of oral rehydration solution (18.45 l) was significantly higher in patients receiving 200 mg doxycycline than in patients receiving either 300 mg doxycycline (16.10 l) or standard tetracycline (14.80 l). Almost equal numbers of patients in each group required unscheduled intravenous acetate solution to correct dehydration during antibiotic treatment. Patients treated with doxycycline (low or high dose), however, had more prolonged excretion of bacteria. CONCLUSIONS: A single 300 mg dose of doxycycline is as effective as the standard multiple dose tetracycline treatment for cholera in terms of stool output, duration of diarrhoea, vomiting, and requirement for oral rehydration solution. PMID- 2196963 TI - ABC of major trauma. Thoracic trauma--I. PMID- 2196964 TI - Microionophoretic study with milacemide, a glycine precursor, on mammalian central nervous system cells. AB - 1. The effect of milacemide, a glycine percursor known to increase gamma aminobutyric acid (GABA) and glycine content in the brain, and to have anticonvulsant properties, was tested by ionophoresis on 247 neurones situated in the cerebral cortex and in deeper structures of cats and rats anaesthetized with urethane. 2. Virtually all the neurones, either firing spontaneously or exogenously driven by the excitatory amino acids, glutamate, N-methyl-D-aspartate (NMDA), kainate and quisqualate or by acetylcholine, were reversibly depressed in a dose-dependent fashion. The same depressant effect was observed in animals pretreated with the monoamine oxidase B inhibitor (IMAO-B) deprenyl which is known to reduce milacemide metabolism into glycinamide and glycine. Intravenous administration of milacemide (10 to 100 mg kg-1) also depressed the firing induced by glutamate, NMDA and acetylcholine. 3. When compared to GABA, milacemide was a weaker depressant. However, its effect could still be observed in the presence of the reversible GABAA antagonist, SR 95531, and thus milacemide is unlikely to act through GABA receptors. In addition, on cells unaffected by glycine, milacemide also had a depressant effect, and on cells inhibited by glycine, it was still capable of depressing cell firing during reversible blockade by strychnine of the glycine inhibitory action; thus milacemide is unlikely to act through glycine receptors. Simultaneous release of milacemide and GABA or of milacemide and glycine, did not show potentiation of the inhibitory amino acid action. However, the depressant effect of milacemide was additive with that of GABA and glycine. 4. No consistent depression of glutamate-induced firing was obtained by ionophoresis of glycinamide, the first metabolite of milacemide. 5. It is concluded that milacemide by itself is a depressant agent and that its depressant effect does not necessarily require its metabolism into glycine, or its stimulator effect on the production of GABA. PMID- 2196965 TI - Effects of indomethacin on the regional haemodynamic responses to low doses of endothelins and sarafotoxin. AB - 1. Regional haemodynamic responses to i.v. bolus injections of low doses (4 pmol and 40 pmol) of endothelin-1, -2, -3 and sarafotoxin-S6b were assessed in conscious, Long Evans rats in the absence and presence of indomethacin. 2. Both doses of endothelin-3 and sarafotoxin-S6b caused early renal vasodilatations that were not affected by indomethacin. Endothelin-1 caused an initial renal vasodilatation only in the presence of indomethacin, indicating that this peptide produced concurrent release of cyclo-oxygenase products that caused renal vasoconstriction. Neither dose of endothelin-2 produced an increase in renal conductance. 3. The 4 pmol dose of all four peptides caused mesenteric vasoconstrictions only. With the 40 pmol dose of the peptides, none caused early mesenteric vasoconstriction except in the presence of indomethacin. Thus, in this vascular bed the primary vasoconstrictor effects of the peptides (seen with the 4 pmol dose) were offset, following the 40 pmol dose, by release of vasodilator cyclo-oxygenase products. Indomethacin alone caused significant vasoconstriction only in the mesenteric vascular bed, indicating that in this region of the circulation, vasodilator prostanoids might be involved also in the tonic control of vascular conductance. 4. All four peptides at both doses caused early hindquarters vasodilatation. However, only the initial hypotensive and hindquarters vasodilator effects of the 40 pmol dose of sarafotoxin-S6b were attenuated by indomethacin. Under these conditions the hindquarters vasodilator effects of sarafotoxin-S6b were similar to those of the other peptides, indicating that the more marked effects of sarafotoxin-S6b in the absence of indomethacin were contributed to by vasodilator cyclo-oxygenase products in the hindquarters. PMID- 2196966 TI - Reactivity and sensitivity of mesenteric vascular beds and aortic rings of spontaneously hypertensive rats to endothelin: effects of calcium entry blockers. AB - 1. The vasoconstrictor effects of endothelin-1 were studied in perfused mesenteric vascular beds (MVB) and aortic rings of 14-16 week-old spontaneously hypertensive rats (SHR) and age-matched Wistar Kyoto rats (WKY). 2. Reactivity to endothelin-1 was increased in MVBs of SHR, as indicated by the maximum perfusion pressure obtained (264 +/- 8 and 141 +/- 9 mmHg respectively) (P less than 0.001), whereas sensitivity was not significantly different between the two strains (EC50 171 +/- 21 and 102 +/- 19, respectively). 3. In aortic rings, in contrast, reactivity to endothelin-1 was reduced in SHR as compared to WKY, whereas sensitivity was similar (EC50 0.78 +/- 0.08 and 0.87 +/- 0.09 nM). 4. As with endothelin-1, reactivity to noradrenaline and potassium chloride was increased in MVBs, but not in aortic rings of SHR. Endothelin-1 was 30 times more potent than noradrenaline in MVBs of SHR, and 15 times more potent than noradrenaline in aortic rings. 5. In both strains, nifedipine and nitrendipine almost completely blocked potassium-induced contractions in MVB and aortic rings, respectively, whereas contractions induced by endothelin-1 or noradrenaline were only partially inhibited. 6. It is concluded that calcium influx via the voltage operated calcium channel is only partially responsible for the vasoconstrictor action of endothelin-1 in MVBs and aortic rings of SHR and WKY rats. The increased reactivity of the MVB of SHR to endothelin-1 at this stage of the hypertensive process is most likely to be the result of a change in vascular structure rather than due to a primary hypertensive mechanism. PMID- 2196968 TI - Video-endoscopy: the remote operating technique. PMID- 2196967 TI - Effects of epithelium removal on relaxation of airway smooth muscle induced by vasoactive intestinal peptide and electrical field stimulation. AB - 1. We have studied the effect of epithelium removal on relaxation of guinea-pig isolated tracheal smooth muscle induced by vasoactive intestinal peptide (VIP) or stimulation of non-adrenergic, non-cholinergic (NANC) inhibitory nerves. Also examined were the effects of inhibitors of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE). 2. Epithelium removal produced a 3.6 +/- 0.4 fold leftward shift in the VIP concentration-response curve. The supersensitivity to VIP, following epithelium removal was abolished by phosphoramidon or thiorphan (NEP inhibitors), but unaffected by captopril (an ACE inhibitor). In intact trachea, the NEP inhibitors produced leftward shifts in the VIP curves similar to those produced by epithelium removal. 3. In contrast to responses to exogenous VIP, neurogenic NANC inhibitory responses to electrical field stimulation were affected neither by epithelial denudation nor by the peptidase inhibitors. 4. As in previous studies, epithelium removal increased tracheal sensitivity to isoprenaline. This was not altered by pretreatment with a cocktail of peptidase inhibitors. Thus, the effect of the NEP inhibitors on responses to VIP appears to be relatively specific. 5. These data indicate that exogenous VIP is a substrate for airway NEP, since inhibition of the enzyme potentiates the peptide. This is further evidence that the airway epithelium provides a source for the metabolism of mediators. 6. In guinea-pig trachea the NEP responsible for cleaving VIP may be located largely in the epithelial layer, since NEP inhibition was without effect on sensitivity to VIP in epithelium-denuded preparations. If VIP is a NANC inhibitory neurotransmitter in this tissue its degradation endogenously does not appear to involve epithelial NEP. PMID- 2196969 TI - Renal transplant biopsy using real time ultrasound guidance. AB - We describe a safe method of percutaneous renal transplant biopsy using real time ultrasound guidance. The method provides a good histological sample, is straightforward and has a low complication rate. PMID- 2196970 TI - Diuretic ultrasound. A non-invasive technique for the assessment of upper tract obstruction. AB - A study was made of the diagnostic reliability of renal ultrasound with a diuretic in the evaluation of upper tract obstruction. The test comprised an initial renal ultrasound examination followed by the intravenous injection of 250 ml physiological saline with 40 mg frusemide; further ultrasound scans were carried out from 5 to 150 minutes later. A total of 67 patients was studied and the results were compared with those of diuretic intravenous urography, diuretic renography and, in some cases, the Whitaker test. Dynamic ultrasound with a diuretic showed a sensitivity of 94%, specificity of 94%, positive predictive value of 91% (obstructive), negative predictive value of 96% (non-obstruction) and a total diagnostic capacity of 94%. PMID- 2196971 TI - Treatment of ureteric colic. Intravenous versus rectal administration of indomethacin. AB - A randomised multicentre clinical trial was undertaken to compare the effect on pain of indomethacin administered either intravenously or rectally to 116 patients with ureteric colic. Adverse reactions were also assessed. Of the patients receiving the intravenous injection, 48/53 (91%) achieved good pain relief (i.e. no supplementary analgesia was required) 30 min after administration, compared with 46/63 (73%) receiving the enema. Significantly more side effects occurred in the group treated intravenously. It was concluded that indomethacin administered as an enema was less effective than the intravenous form, but it should be regarded as a good alternative in the treatment of ureteric colic. PMID- 2196972 TI - Intraprostatic antibody deposition in chronic abacterial prostatitis. AB - Sixty patients with chronic abacterial prostatitis and 21 men without prostatitis were studied. Transperineal prostatic biopsies taken under transrectal ultrasound control were examined for antibody, complement (C3) and fibrinogen deposition using a direct immunofluorescence (IF) technique; 34 patients (57%) had prostatic tissue that displayed IF staining compared with only 1 (5%) in the non prostatitis group. IF staining for IgM was found in 85%, for C3 in 44%, for IgA in 35% and for fibrinogen in 24%, but the IgG subclass was not detected. Antibody deposition was mainly periglandular and glandular and in the wall of vessels. Five symptoms, particularly poor urinary flow, irritative voiding and urgency, were significantly correlated with IgM and C3 deposition and, to a lesser extent, fibrinogen deposition. The aetiology of chronic abacterial prostatitis remains obscure but several possible mechanisms are discussed. The link between symptomatology and immunology could rest with functional outflow obstruction causing intraprostatic reflux of urine, this in turn inciting an immunological response, the inducing antigens being organism remnants or products, urinary constituents or autoantibodies. PMID- 2196973 TI - Risk of recurrent stricture following internal urethrotomy. Prospective ultrasound study of distal male urethra. AB - A group of 60 patients was examined prior to surgery in a prospective ultrasound study of the distal male urethra to predict the individual rate of stricture recurrence after internal urethrotomy. The patients were divided into 2 groups according to the ultrasound findings. One group had no evidence of scarred tissue and no recurrence was predicted. The other group did have periurethral scarring and stricture recurrence within approximately 6 months was predicted. We present the ultrasound findings and discuss the accuracy of the predictions. Correct prognoses were made in 92.9% of cases. PMID- 2196974 TI - Endoscopic correction of vesicoureteric reflux in children with spina bifida. AB - Twenty patients with vesicoureteric reflux (VUR) secondary to a neuropathic bladder and associated spina bifida were treated with the endoscopic injection of subureteric polytetrafluoroethylene (Teflon) paste. Of the 19 patients (29 ureters) followed up, 13 have persistent reflux, although only 3 of these ureters have needed a second injection. Twelve of the 16, where reflux resolved, required only 1 injection. PMID- 2196975 TI - Retrovirus-mediated gene transfer into mouse cerebellar primary culture and its application to the neural transplantation. AB - To develop a procedure for the transplantation of genetically modified brain primary cells, we transplanted cultured mouse cerebellar cells infected with recombinant retroviruses into the cerebella of adult mice and examined the expression of introduced gene-products in the host cerebellum after transplantation. After infection of cultured cerebellar cells with recombinant retroviruses harboring chloramphenicol acetyltransferase (CAT) gene, we selected only virus-infected cells for transplantation by culturing the cells in medium containing G418 for 3 weeks. CAT was continuously expressed in the cultured cerebellar cells during the 3-week incubation, but by immunoblotting analysis with antiglial fibrillar acidic protein (GFAP) or antineurofilament protein (NFP) antiserum the population of cultured cerebellar cells was found to change during the incubation. Immunocytochemical analyses using anti-CAT antiserum demonstrated that the transplanted cell mass containing CAT-positive cells was detectable in the cerebellum up to 3 weeks, but not 3 months after the transplantation of G418 selected cells into the cerebella of 7-week-old mice. PMID- 2196976 TI - Effects of quisqualic acid nucleus basalis lesioning on cortical EEG, passive avoidance and water maze performance. AB - The study examines the effects of unilateral quisqualic acid nucleus basalis (NB) lesioning on cortical EEG and learning behavior. Lesions produced both gliosis in the ventral pallidum and a marked reduction in the cortical ChAT activity. Normal cortical EEG activity was abolished on the side of NB lesion, i.e., slow wave activity and the incidence of high voltage spindles was higher on the side of lesion compared with the control side. NB lesioning impaired passive avoidance retention, but not spatial learning ability. These results suggest that EEG and passive avoidance deficits induced by NB quisqualic acid lesion may result from the damage specifically to cholinergic neurons. Thus, the restoration of EEG and passive avoidance performance defects in quisqualic-lesioned rats may be used as an index of the efficacy of the cholinergic replacement therapies. PMID- 2196978 TI - [The battle of schizophrenia]. AB - The notion of "dementia praecox" was introduced by Kraeplin to create a new mental illness like dementia paralytica of Bayle. Afterwards this new illness was called schizophrenia by Bleuler. From more half a century. I have studied this illness, specially the "Catatonia" theses researches pointed that catatonia is not an incurable disease but is a toxic reaction especially to colibacillar toxin and others toxins. I could reproduce the catatonia in animals with several toxics (in the beginning with de Jong from Amsterdam with bulbocapnine and afterwards with other toxins). To conclude, psychiatry must remain a part of general medicine with the arm of complete cura and with human feelings. PMID- 2196977 TI - Macrophage inflammatory protein-1: unique action on the hypothalamus to evoke fever. AB - Macrophage inflammatory protein (MIP-1) administered systemically causes a fever not blocked by a prostaglandin (PGE) synthesis inhibitor. The purpose of this study was to examine the central mechanism of pyrexic action of this cytokine in the unrestrained rat. After guide cannulae for microinjection were implanted stereotaxically just above the anterior hypothalamic preoptic area (AH/POA), the body temperature of each rat was monitored by a colonic thermistor probe. Saline control vehicle or MIP-1 was microinjected into the AH/POA in one of eight concentrations ranging from 0.0028-9.0 ng per 0.5 mu 1 volume. MIP-1 induced a biphasic or monophasic fever of short latency characterized by an inverse dose response curve. The potency of MIP-1 was in the femtomolar (10(-15)) range with the lowest dose of 0.028 ng producing a fever of over 2.0 degrees C with a latency of 15 min or less. To determine whether a PGE mediates MIP-1 fever, indomethacin was administered either intraperitoneally in a dose of 5.0 mg/kg or directly into the MIP-1 injection site in a dose of 0.5 microgram/0.5 mu 1, both injected 15 min before MIP-1. Pretreatment of the injection site in the AH/POA with indomethacin failed to prevent the febrile response evoked by MIP-1 injected at the same locus. Further, the dose of systemic indomethacin, which blocks PGE induced fever in the rat, attenuated only partially the MIP-1 fever. The results demonstrate that MIP-1 is the most potent endopyrogen discovered thus far, and that its action is directly in the region of the hypothalamus which contains both thermosensitive and pyrogen-sensitive neurons. The local action of MIP-1 on cells of the AH/POA in evoking fever is unaffected by the PGE inhibitor which indicates, therefore, that a cellular mechanism operates in the hypothalamus to evoke fever independently of the central synthesis of a PGE. PMID- 2196979 TI - The laryngeal mucocele. Imaging analysis of a rare lesion. AB - Four patients with laryngeal mucocele (fluid-filled laryngocele) are described. Two laryngeal mucoceles were external, lying outside the thyrohyoid membrane, and two were combined, lying both internal and external to the membrane. The combined laryngeal mucoceles presented with both neck mass and hoarseness. The external lesions and one combined lesion were diagnosed using computed tomography (CT) and ultrasound. Another combined lesion had the benefit of CT and magnetic resonance imaging (MRI) prior to exploration. All were homogeneously hypodense at CT with rim enhancement only in the case of the laryngopyocele. The mucocele evaluated with MRI had homogeneously long T1 and T2 relaxation times similar to cerebrospinal fluid. PMID- 2196980 TI - Imaging of prenatally detected intra-abdominal extralobar pulmonary sequestration. AB - Intra-abdominal extralobar pulmonary sequestration is a rare congenital anomaly which may present as an abdominal mass. We describe a case of intra-abdominal extralobar pulmonary sequestration detected prenatally as a left suprarenal mass. The ultrasound, computed tomography and magnetic resonance imaging findings are illustrated and correlated with the pathologic findings. PMID- 2196981 TI - Empyema of the gallbladder in a patient with AIDS-related complex. AB - A case of staphylococcus aureus empyema of the gallbladder in a patient with AIDS related complex is presented. The case is remarkable for the indolence of the clinical presentation and the magnitude of gallbladder dilatation noted at computed tomographic (CT) examination. Empyema of the gallbladder may constitute an unusual manifestation of bacterial disease in patients with AIDS or AIDS related complex and cholelithiasis. PMID- 2196982 TI - Problematic renal masses in ultrasonography and computed tomography. AB - The diagnosis of renal masses is based upon the contribution of ultrasonography (US) and computed tomography (CT), which enable the recognition of these lesions with high diagnostic accuracy. However, a number of diagnostic difficulties exist in the definition of the nature of the mass, both for cystic and solid lesions, and to a lesser extent in the identification of the mass. "Complicated" cystic masses, such as calcified cysts, hemorrhagic cysts, inflammatory cysts, abscesses, and cystic tumors may be difficult to diagnose with US and sometimes with CT. CT is helpful in most of these cases because it enables the evaluation of the calcifications and the density of the fluid content. CT is also helpful in cases of cystic tumors because it shows the enhancement of septae within the masses. Problems with solid masses are the identification of small renal tumors and the definition of the benign or malignant nature of the mass. Although both techniques enable the recognition of most tumors, even if small in diameter, they are still limited in defining the pathological structure of the tumor. PMID- 2196983 TI - Expression and catalysis of sex-specific cytochrome P450 isozymes in rat liver. AB - Research interest in the study of cytochromes P450 has recently been shifting to the characterization of "constitutively" expressed isozymes from that of the inducible forms. Several "constitutive" cytochrome P450 isozymes have been purified from rat liver including five immunochemically related proteins designated cytochromes P450f, P450g, P450h, P450i, and P450k. These hemoproteins have been identified as distinct isozymes on the basis of spectral, electrophoretic, and catalytic properties and NH2-terminal sequence analysis. Purification and immunoquantitation studies have indicated that these isozymes are expressed in a developmental as well as sex-related manner, and are relatively refractory to induction by xenobiotics. Cytochromes P450h and P450g are male-specific proteins, cytochrome P450i is a female-specific isozyme, while cytochromes P450f and P450k are present in both male and female adult rats. In addition, the expression of cytochrome P450g was shown to segregate into two phenotypes in outbred rats. Genetic studies utilizing inbred strains have indicated that the gene responsible for inheritance of high levels of cytochrome P450g is autosomal. Although considerable progress has been made in understanding the role of gonadal hormones and growth hormone in the hepatic regulation of cytochromes P450g, P450h, and P450i in particular, the physiological significance of the "constitutive" isozymes in the liver remains largely unresolved. PMID- 2196984 TI - On the usefulness of the DSM-III-R versus the DSM-III for child psychiatrists. AB - The purpose of this paper is to compare and contrast the disorders of infancy, childhood and adolescence in the DSM-III-R with those of its predecessor, the DSM III. Design features of the child psychiatry sections of the DSM-III-R are described, with comparisons of reliability and validity assessments in the two classifications. Categorical and dimensional systems of psychiatric nosology are described; the DSM-III-R has features of both systems. To be most useful for child psychiatrists in ordinary clinical practice, DSM-III-R symptom criteria should be available in a standardized but brief fashion to ensure adequate data gathering from both child and parent. This avoids problems inherent in lengthy standardized interviews are based on DSM-III-R criteria; although these interviews are excellent for research purposes, clinicians tend to avoid them as clinically constraining. The commonly used alternate of clinicians' overall evaluations is of uncertain reliability and validity, since it is unclear whether all symptoms have been asked for. A symptom checklist approach is therefore suggested as a intermediate procedure to ensure that appropriate questions are asked from the parent and child, while allowing fuller exploration by the clinician. This approach also indicates parent-child variance, and allows for rank ordering of diagnoses which may indicate priorities for treatment of child psychiatric disorders. Overall, the DSM-III-R is a positive step towards more adequate diagnosis and treatment for child and adolescent psychiatric disorders, which will lead to further improvement in the future DSM-IV. PMID- 2196985 TI - Contributions of epidemiology to psychiatric thought. AB - As a result of trying to apply both science and humanism to psychological problems, psychiatry is exposed to a welter of confusing issues in which science and intuition are pitted against each other. A growing awareness of the importance of quantification in clinical research and theory construction is having the effect of increasing the polarization. It is suggested in this paper that Karl Jaspers' formulation of erklaren and verstehen provide a conceptual frame by which orderly relationships can replace much of the confusion and polarization. It is further suggested that this line of thought can be implemented and developed by the use of epidemiologic strategies. Historic and recent examples from the literature are provided in order to illustrate how this can be done. PMID- 2196986 TI - Psychiatric epidemiology in Quebec: an overview. AB - This paper reviews the development of psychiatric epidemiology in Quebec from 1960 to the present. The research in this area is divided into three periods: 1960 to 1980, 1980 to 1985, and 1985 onward. Child psychiatric epidemiology is addressed separately. The authors conclude that psychiatric epidemiology has been an active area of research in Quebec and will likely be even more so in the future given the increasing interest in the field. PMID- 2196987 TI - N-myc oncogene and stage IV-S neuroblastoma. Preliminary observations on ten cases. AB - We studied the clinical significance of genomic amplification of N-myc in Stage IV-S neuroblastoma, with reference to spontaneous regression. Among 103 neuroblastomas in which N-myc was measured, ten were Stage IV-S (eight children were younger than and two were older than 1 year of age). The number of copies of N-myc was 1 to 3 in five patients, four to ten in one patient, and more than ten in four patients, and the survivors of each group were four, one, and one (recurrent), respectively. Of 41 patients younger than 1 year of age, N-myc amplification of more than three copies was found only in Stage IV-S neuroblastoma. Cure with a tendency to regress spontaneously was seen in five of eight patients younger than 1 year of age. However, two patients older than 1 year of age classified as Stage IV-S (one with N-myc amplification) died of progressive disease. In two patients (1 and 3 months of age) with a huge hepatic involvement and in whom the tumor had an amplified N-myc of more than ten copies, tumor regression occurred but there was a relapse to a progressive state later. The overexpression of N-myc mRNA occurred in nine of ten stage IV-S tumors and did not correlate with the prognosis. The vanillylmandelic acid (VMA) to homovanillic acid (HVA) ratio was low in tumors with an increased number of copies of N-myc. Serum lactate dehydrogenase (LDH) levels were increased in Stage IV-S patients with N-myc amplification but not in those with regressing tumors and without N-myc amplification. These data suggest that N-myc amplification may affect the final outcome in the patient classified as Stage IV-S, but tumor regression can occur early after birth and appears to be independent of N-myc amplification. PMID- 2196988 TI - Establishment of a human undifferentiated thyroid cancer cell line producing several growth factors and cytokines. AB - A cell line was established from undifferentiated giant cell carcinoma of the thyroid. The authors obtained cells from a 44-year-old patient admitted because of a rapidly growing anterior neck mass. The patient had significant leukocytosis and hypercalcemia shortly before her death. An autopsy revealed epidermoid metaplasia of the tumor cells. The cells (HTC/C3) had lost most of their differentiated functions. However, their thyroid nature was shown by peroxidase staining and by enzyme-linked immunostaining with Hashimoto patients' sera. The tumor extract was found to contain parathyroid (PTH)-like activity. Significant amounts of colony stimulating factor (CSF), which was further defined to be GM CSF, and interleukin-1 alpha (IL-1 alpha) were detected in the conditioned media. Epidermal growth factor (EGF) binding to the HTC/C3 showed rich EGF receptors. Furthermore, the conditioned medium inhibited the binding of 125I-mEGF to HeLa cells, and transforming growth factor (TGF) was found repeatedly in the media. PMID- 2196989 TI - A cell culture, chromosomal and quantitative DNA analysis of a metastatic epithelioid sarcoma. Deletion 1p, a possible primary chromosomal abnormality in epithelioid sarcoma. AB - The chromosomal banding pattern and the in vitro growth characteristics of a metastatic epithelioid sarcoma are described. The cultured tumor cells retained growth characteristics as well as ultrastructural and immunohistochemical properties similar to the cells of the primary tumor. Cytogenetic analysis revealed a modal range in the diploid-hypodiploid region, a finding which was corroborated by quantitative DNA determinations of both the primary tumor and a lymph node metastasis. Fourteen different marker chromosomes were identified. The most frequent clonal rearrangement was a 1p-marker resulting from a short arm terminal deletion, i.e., del (1) (p21-22). A similar 1p- marker has previously been observed in an established epithelioid sarcoma cell line. The finding of an apparently identical 1p-marker in two of two analyzed epithelioid sarcomas suggests that this rearrangement may be a primary cytogenetic abnormality in epithelioid sarcoma. An elevated ras p21 expression was demonstrated using immunohistochemical methods. The possible involvement of the N-ras gene and/or a tumor suppressor in the 1p deletion is considered. PMID- 2196991 TI - [The history of social pediatrics in Ostrava]. PMID- 2196990 TI - Epidermal Langerhans' cell densities influence survival in mycosis fungoides and Sezary syndrome. AB - Because Langerhans' cells (LC) (CD1a-positive epidermal cells) have been discussed to be involved in the pathogenesis of mycosis fungoides and Sezary syndrome, the authors examined the influence of densities of Langerhans' cells and, concurrently, of other phenotypes retrospectively on survival of 35 patients. Cell densities were assessed on cryostat sections (alkaline phosphatase antialkaline phosphatase-technique) of the respective diagnostic biopsy specimens. Additionally, two clinical parameters (age, stage of disease) were evaluated. CD1a-positive epidermal cells were demonstrated to be the only cell population being significantly associated (P = 0.011) with survival. Death resulting from mycosis fungoides and Sezary syndrome was significantly (P = 0.003) less frequent in patients with epidermal CD1a-positive cell densities higher than 90 cells/mm2 (optimal break point) as compared with patients with lower numbers. These results suggest that Langerhans' cells have a significant impact on prognosis of patients with mycosis fungoides and Sezary syndrome. They play an important role in the host defense mechanisms against these lymphomas rather than to favor their progression as proposed recently. PMID- 2196992 TI - [Epidemiologic trends in dengue fever and dengue hemorrhagic fever]. PMID- 2196993 TI - [The progress in the research of disinfection and sterilization of the hepatitis B virus]. PMID- 2196994 TI - Polarized sorting in epithelia. PMID- 2196995 TI - A candidate protein kinase C gene, PKC1, is required for the S. cerevisiae cell cycle. AB - Probes derived from cDNAs encoding isozymes of rat protein kinase C (PKC) were used to screen the genome of the budding yeast S. cerevisiae. A single gene (PKC1) was isolated that encodes a putative protein kinase closely related to the alpha, beta, and gamma subspecies of mammalian PKC. Deletion of PKC1 resulted in recessive lethality. Cells depleted of the PKC1 gene product displayed a uniform phenotype, a characteristic of cell division cycle (cdc) mutants, and arrested cell division at a point subsequent to DNA replication, but prior to mitosis. Unlike most cdc mutants, which continue to grow in the absence of cell division, PKC1-depleted cells arrested growth with small buds. PKC1 may regulate a previously unrecognized checkpoint in the cell cycle. PMID- 2196996 TI - Assembly of MHC class I molecules analyzed in vitro. AB - Recent evidence suggests that peptide ligands take part in the assembly of class I molecules in living cells. We now describe a simple system for studying class I assembly in vitro. Detergent extracts of the mutant cells RMA-S and .174, in which class I assembly does not occur spontaneously, will support assembly in vitro when specific peptides are added. Peptides stabilize a conformational change in the class I heavy chain and association with beta 2-microglobulin, at concentrations approximately 100-fold lower than required in "peptide feeding" experiments with whole cells. We show that peptides bind class I molecules during assembly and demonstrate that the conformational change induced in the heavy chain is influenced by the concentrations of both peptide and beta 2 microglobulin. PMID- 2196997 TI - Regulation of insulin receptor functions by a peptide derived from a major histocompatibility complex class I antigen. AB - A 25 residue peptide, Dk-(61-85), derived from the alpha 1 domain of a murine MHC class I molecule (H-2Dk), enhances cellular glucose uptake, prolongs the effect of insulin, and inhibits insulin receptor internalization without affecting insulin binding or dissociation. Full effect of the peptide is obtained at 10-100 microM. The magnitude of the peptide-mediated enhancement of glucose uptake is insulin dependent and is at maximum approximately 50% above that of full insulin stimulation, excluding a merely insulinomimetic action of the peptide. Dk-(61-85) does not interact directly with the glucose transporter molecule. Furthermore, the peptide-mediated inhibition of insulin receptor internalization results in 2 3 times more receptors in the plasma membrane. The peptide also causes hypoglycemia in rats. The biological activity of Dk-(61-85) suggests that an important nonimmunological role of MHC class I molecules is to affect some of the key functions of ligand-activated receptors. PMID- 2196998 TI - [Epidemiology of vaginal mycoplasmas]. AB - The authors made in 456 women mycoplasmatological examinations of the vaginal secretion by cultivation. Mycoplasma hominis was obtained in 158 women (34.6%). U. urealyticum in 295 women (64.7%) In 120 women (26.3%) both microorganisms were present. The prevalence of vaginal mycoplasms is markedly influenced by the sexual activity of women. The relative risk of colonization of the vagina with M. hominis rises with the frequency of sexual intercourse more than four times. In case of a larger number of sexual partners the relative risk of colonization of the vagina with U. urealyticum is 7.7 times higher than in women with a single partner. PMID- 2196999 TI - [Extrauterine localization of an IUD]. PMID- 2197000 TI - [New possibilities in the prevention and therapy of EPH gestosis]. PMID- 2197001 TI - Clear fluids three hours before surgery do not affect the gastric fluid contents of children. AB - This prospective, randomized, single-blind study of 121 healthy children aged 2 to 12 yr investigated the effect of clear fluids on gastric contents. Gastric fluid volume and pH were measured immediately following the induction of general anaesthesia and were not significantly affected by the ingestion of unlimited clear fluids up to three hours preoperatively. After a prolonged fast (mean fast 14 hr), gastric fluid volume was 0.39 +/- 0.37 ml.kg-1 and gastric pH was 1.7 +/- 0.4; after unlimited clear fluids (203 +/- 109 ml) up to three hours before surgery gastric fluid volume was 0.34 +/- 0.28 ml.kg-1 and gastric pH was 1.8 +/- 0.7 (mean +/- SD). Gastric fluid volume (ml.kg-1) increased in both the control and study groups as age increased, P less than 0.005. It is concluded that drinking clear fluid up to three hours before scheduled surgery does not have a measurable effect on gastric volume and pH of healthy children of ages 2 to 12 yr. PMID- 2197002 TI - Propofol infusion anaesthesia for caesarean section. AB - Two propofol infusion regimens and a standard general anaesthetic were compared in thirty Chinese women undergoing elective Caesarean section. After induction of anaesthesia with propofol 2 mg.kg-1, ten patients received propofol 6 mg.kg-1.hr 1 and nitrous oxide 50 per cent in oxygen while ten were given propofol 9 mg.kg 1.hr-1 with 100 per cent oxygen. The other ten patients received thiopentone 4 mg.kg-1 and nitrous oxide 50 per cent in oxygen with enflurane one per cent. Maternal recovery times and psychomotor performance were recorded. Neonates were assessed by Apgar scores, neurologic and adapative capacity scores (NACS) and umbilical cord blood gas analysis. Haemodynamic changes were similar immediately following induction but the low propofol infusion group had the best haemodynamic stability subsequently. Recovery times were fastest in the low-infusion group but there were no differences in later postbox testing. Neonatal Apgar scores and umbilical blood gas analysis were similar but NACS at two hours were poorer in the high infusion group. A propofol infusion coupled with nitrous oxide appears to be a satisfactory technique for Caesarean section. PMID- 2197003 TI - A randomized comparison of midazolam and diazepam injectable emulsion in cataract surgery. AB - The purpose of this study was to compare the psychomotor recovery of patients sedated with either midazolam or Diazemuls using the digit symbol substitution test and the Trieger test. Sixty patients were allocated in random double-blind fashion to receive either midazolam or diazepam in oil emulsion (Diazemuls) as intravenous sedation for cataract surgery. Both groups received fentanyl 0.5 micrograms.kg-1 IV. Tests of cognition were performed by the patients prior to sedation and at half-hourly intervals for three hours after cataract surgery. In a dose ratio of 1:4, midazolam was found to produce better sedation but more prolonged recovery than Diazemuls. Anterograde amnesia was comparable in the two groups, while more patients in the Diazemuls group developed episodes of apnoea and venous irritation. PMID- 2197004 TI - [Lidocaine aerosol following tonsillectomy in children]. AB - Post-tonsillectomy analgesia was compared using ten per cent aerosol lidocaine or 1.5 mg.kg-1 intramuscular codeine. Thirty ASA physical status I or II children between two and ten years of age were assigned, in a random fashion, to one of two groups: Group A received codeine 1.5 mg.kg-1 intramuscularly, Group B received a total dose of 4 mg.kg-1 of ten per cent aerosol lidocaine on the tonsillar beds. For both groups, the treatment was administered at the end of the surgical procedure. The postoperative comfort state was assessed on a global scale using the following statement: (1) comfortable = 1, (2) agitation = 2, (3) uncontrollable = 3. Assessment of postoperative comfort was recorded after 20 min in the post-anaesthetic recovery room. Blood samples for lidocaine concentration estimation were obtained at 5, 7.5, 10, and 15 min after administration. Finally, the time of recovery was recorded. The immediate post-anaesthetic comfort observed with ten per cent aerosol lidocaine was statistically superior to that obtained with 1.5 mg.kg-1 intramuscular codeine. The maximal systemic lidocaine concentration which was 2.1 +/- 0.2 micrograms.ml-1 was well below the accepted toxic level of 5.3 micrograms.ml-1. The recovery room times were not statistically different between the two groups. In conclusion, 4 mg.kg-1 of ten per cent aerosol lidocaine applied directly on the tonsillar beds was shown a superior immediate post-tonsillectomy analgesic technique. PMID- 2197005 TI - Comparison of intrathecal meperidine and lidocaine in endoscopic urological procedures. AB - The purpose of this study was to determine if a small dose of intrathecal meperidine would achieve adequate spinal anaesthesia while minimizing complications and to compare its effectiveness with lidocaine. The spinal anaesthetic effects of five per cent lidocaine 0.5 mg.kg-1 in 7.5 percent glucose (n = 20) or five per cent meperidine 0.5 mg.kg-1 (n = 22) were evaluated in 42 ASA physical status II or III patients. Intrathecal injection of the anaesthetic agent was given with the patient in the sitting position in which he remained for ten minutes before being placed in the lithotomy position. The onset time for sensory blockade was seven minutes in the lidocaine group and ten minutes in the meperidine group. Final sensory levels were identical in both groups. Mean arterial blood pressure decreased significantly in the lidocaine group but not in the meperidine group. Motor block was absent in ten patients in the meperidine group but was present in all the patients in the lidocaine group. Duration of postoperative analgesia was 968 min in the meperidine group and 681 min in the lidocaine group (NS). Complications such as nausea, vomiting, itching, drowsiness and respiratory depression were similar in the two groups. It is concluded that low-dose meperidine, 0.5 mg.kg-1, is effective as a spinal anaesthetic agent and has few complications. PMID- 2197006 TI - Anaesthetic implications for bone marrow transplant recipients. PMID- 2197007 TI - History of Canadian anaesthesia. Dr. C.H. Robson (1884-1969). PMID- 2197009 TI - Gap junctional intercellular communication and carcinogenesis. PMID- 2197008 TI - Intraoperative anaphylaxis to latex. AB - This case report describes intraoperative anaphylaxis occurring in a fourteen year-old female with spina bifida in which latex surgical gloves were incriminated as the aetiologic agent. The patient was non-atopic but since eight years of age she had developed localized angioedema and urticarial skin reactions on exposure to rubber. She had previously undergone several uneventful surgical procedures. Forty-five minutes following induction of anaesthesia and during laparotomy for elective cholecystectomy she experienced sudden onset of increased airway pressure, oxygen desaturation, tachycardia, profound hypotension and erythema consistent with an anaphylactic reaction. Resuscitation with manual ventilation and oxygen, intravenous fluids and an epinephrine infusion was successful. Subsequent investigations for allergies demonstrated a strongly positive skin prick test and RAST to latex antigen, with negative results to anaesthetic agents, antibiotics and inhalant allergens. During two later operations prophylaxis consisting of diphenhydramine, ranitidine and hydrocortisone appeared to prevent further reactions. Latex should be considered as a cause of life-threatening intraoperative allergic reactions in patients with a history of rubber allergy or frequent exposure to latex products. PMID- 2197010 TI - N-acetoxy-N-acetyl-2-aminofluorene-induced mutagenesis in the lacI gene of Escherichia coli. AB - To study the mechanisms of mutagenesis by the carcinogen N-acetyl-2-aminofluorene (AAF), we determined by DNA sequencing the spectrum of mutations in the Escherichia coli lacI gene induced by the ultimate metabolite N-acetoxy-N-acetyl 2-aminofluorene, using an E. coli derivative with increased permeability to this compound. Several different classes of mutations were recovered, including base substitutions (11%), single-base frameshifts (11%), double-base frameshifts (22%), deletions (21%), duplications (2%) and 'spontaneous hot-spot' mutations [26%; the gain (19%) or loss (7%) of TGGC at the sequence TGGCTGGCTGGC]. Among the base substitutions, both transitions and transversions occurred. The single base frameshifts were all the loss of a base. The double-base frameshifts represented the loss of a (GpC) or (ApC) dinucleotide from alternating (GpC)n or (ApC)n sequences. The deletion, duplication and hot-spot mutations showed relative G,C-richness at their endpoints, suggesting that AAF-induced lesions at or near the endpoints promoted their occurrence. Taken together, the data are consistent with several previous findings on AAF mutagenesis, extending in particular the importance of frameshift mutagenesis at alternating purine pyrimidine sequences and establishing deletion and duplication mutations as an important consequence of treatment with this carcinogen. PMID- 2197012 TI - Activation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) to mutagenic metabolites. AB - Metabolism of heterocyclic amines to N-hydroxy intermediates appears critical in the mutagenic and carcinogenic actions of these compounds. We have studied the murine hepatic microsomal and cytosolic activation of 2-amino-1-methyl-6 phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine mutagen formed in cooked meats. PhIP (25 microM) was almost completely converted to N-hydroxy-PhIP and 4'-hydroxy-PhIP in 30 min by reaction with 3-methylcholanthrene-induced microsomal preparations. Microsomal formation of the active N-hydroxy-PhIP metabolite was slightly favored over the 4'-hydroxy-PhIP detoxification product at all concentrations studied (25-200 microM). Metabolism of PhIP in microsomal preparations derived from control mice was approximately 10% of the induced preparations. Metabolically activated PhIP and synthetic N-hydroxy-PhIP produced concentration-dependent increases in mutagenic activity in both Salmonella strains TA98 and TA98/1,8-DNP6, indicating that acetylated intermediates were not important in the mutagenicity of N-hydroxy-PhIP in these bacteria. Significant stabilization of the N-hydroxy-PhIP intermediate by both microsomal protein and BSA was observed. Addition of cytosol to microsomal incubations with PhIP (25 microM) resulted in an increase in mutagenic activity which could be attributable to stabilization by glutathione. An additional increase in mutagenicity resulted from addition of 3'-phosphoadenosine 5'-phosphosulfate (PAPS), but not acetyl coenzyme A to microsomal preparations containing the cytosolic fraction. Furthermore, addition of PAPS to cytosolic preparations containing synthetic N hydroxy-PhIP produced a 17% decrease in levels of the arylhydroxylamine relative to controls over 30 min, suggesting that secondary metabolism of N-hydroxy-PhIP to a sulfate conjugate may be relevant to the mutagenic and carcinogenic actions of PhIP. PMID- 2197011 TI - Regulation of rat hepatocyte epidermal growth factor receptor by the liver tumor promoter ethinyl estradiol. AB - We have previously demonstrated that the liver tumor promoter ethinyl estradiol (EE) greatly enhanced the DNA synthetic response of rat hepatocytes in primary culture to epidermal growth factor (EGF). This effect was associated with a 2 fold increase in surface EGF receptor number. In this report, we demonstrate that the increase in cell surface [125I]EGF binding caused by EE is time dependent, beginning at 8 h and reaching a plateau at 18 h. This increased EGF binding was accompanied by a comparable increase in the amount of total EGF receptor protein. In vivo, EE treatment also increased the number of EGF binding sites. EE treatment did not increase the rate of [35S]methionine incorporation into immunoprecipitated EGF receptor protein, nor did it appear to affect the steady state levels of EGF receptor mRNA compared to that found in controls. However, EE treatment did cause an increase in the half-life of EGF receptor protein from 4.5 +/- 0.5 h in control hepatocytes to 10.4 +/- 1.8 h. Taken together, these results indicate that the EE-induced 2-fold increase in EGF receptor levels, which is associated with the potentiation of responsiveness to EGF, was brought about by stabilization of receptor protein. PMID- 2197013 TI - Negative results of short-term genotoxicity tests with 1,4-bis[2-(3,5 dichloropyridyloxy)]benzene. AB - The phenobarbital-like enzyme inducer and tumor promoter of murine hepatocarcinogenesis, 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene has been assayed in short-term genotoxicity tests, i.e. the Salmonella mutagenicity test, micronucleus and chromosomal aberrations analysis in mouse bone marrow cells in vivo, DNA alkaline elution and DNA unwinding assays in mouse liver in vivo. All the assays performed proved negative. PMID- 2197014 TI - Characterization of dihydrodiol dehydrogenase in human liver and lung. AB - Dihydrodiol dehydrogenase (DD; EC 1.3.1.20) will oxidize non-K-region trans dihydrodiols of polycyclic aromatic hydrocarbons (PAHs), a reaction that can suppress the formation of PAHs) anti-diol epoxides or ultimate carcinogens. Using benzenedihydrodiol [(+/-)-trans-1,2-dihydroxy-3,5-cyclohexadiene] as a model substrate for trans-dihydrodiol metabolites of PAHs, 23 human liver and eight human lung samples were examined for enzyme activity. In human liver, enzyme activity could be measured spectrophotometrically and specific activities ranged from 0.16 to 6.1 nmol benzenedihydrodiol oxidized min/mg protein. Western blot analysis of human liver cytosol using rabbit anti-rat DD serum detected two bands of mol. wts 34,000 and 27,000. The former mol. wt is identical to that observed for the homogeneous rat liver enzyme. Gel-filtration experiments indicate that human liver DD activity elutes as a single peak and co-elutes with the purified rat liver enzyme, suggesting that the lower mol. wt species may be an artefact of degradation. Preparations of the human liver enzyme required NADP- for activity and were in general, insensitive to inhibition by dicoumarol, indomethacin and 6 medroxyprogesterone acetate. These properties distinguish the enzyme from alcohol dehydrogenase, quinone reductase and rat liver DD. In human lung, DD activity was barely detectable using a sensitive radiochemical assay in which the oxidation of benzenedihydrodiol to catechol is linked to catechol-O-methyl transferase using [3H]S-adenosyl methionine as methyl donor. Specific activities were approximately 1000th of that observed for human liver and ranged from 1 to 4 pmol benzenedihydrodiol oxidized/min/mg protein. Western blot analysis of lung cytosol detected three bands of mol. wts 34,000, 31,000 and 28,000. The relatively high levels of DD in human liver suggest that this enzyme may play an important role in PAH detoxication in this organ, while the low levels of DD in lung may contribute to the susceptibility of this tissue to PAH-induced carcinogenesis. PMID- 2197015 TI - Induction and purification of O6-methylguanine-DNA-methyltransferase from rat liver. AB - O6-Methylguanine-DNA-methyltransferase (OMMT) is a DNA repair protein that plays an important role in chemotherapy, mutagenesis and carcinogenesis. The sp. act. of OMMT in rat liver can be induced by approximately 12- to 20-fold by treatment of the rats with ionizing radiation. The effects of dose and time were investigated in this study. We have found that OMMT sp. act. can be increased, although to a lower extent, in kidney, spleen and brain in addition to liver. However, the sp. act. of OMMT in lung was reduced by irradiation. OMMT has been purified from the livers of irradiated rats by solubilization in high-salt containing buffer, ammonium sulfate precipitation and a series of column chromatographic steps, including phenyl-Sepharose, heparin-agarose, double stranded DNA-cellulose and FPLC. A 3000-fold enrichment of OMMT was achieved from the induced liver preparations. However, with regard to the sp. act. of this protein in normal rat liver, the fold purification was approximately 35,000. After methylation, OMMT during the course of its action exhibited a mol. wt of 28 kd under SDS-PAGE conditions. PMID- 2197016 TI - Genetic mechanisms that determine oxidative capacity of striated muscles. Control of gene transcription. PMID- 2197017 TI - Role of neural crest in congenital heart disease. PMID- 2197018 TI - Automated quantitation of indexes of coronary lesion complexity. Comparison between patients with stable and unstable angina. AB - Analysis of lesion morphology is becoming increasingly important in the study of coronary artery disease. Lesion irregularity has been shown to be one of the most important predictive features for development of myocardial infarction. Most studies to date have used only qualitative assessments of morphology and are thus subject to variability and lack of standardization inherent in subjective visual inspection. We describe a new approach that allows quantitation of lesion morphology. Fifty-nine patients with unstable angina and 17 patients with stable angina were compared. Five morphometric parameters were tested (peaks per centimeter, summed maximum error per centimeter, integrated error per centimeter, number of major features per centimeter, and scaled edge length ratio), four of which were significantly different between the two groups and indicated greater lesion complexity in unstable compared with stable angina patients. No correlation was found between the parameters tested and the degree of luminal narrowing, showing the method's independence from traditional assessments of lesion severity. Excellent intraobserver and interobserver reproducibility was found for all of the parameters. This technique provides a more rigorous approach for analysis of lesion morphology than has previously been available, may provide a method for premorbid detection of high-risk lesions amenable to interventional therapy, and is especially well suited to detect subtle changes in lesion morphology after therapeutic interventions because the parameters are derived on a continuous scale and are not categorical. PMID- 2197019 TI - Cardiovascular effects of fish oils. Beyond the platelet. PMID- 2197020 TI - Sudden cardiac death in children. PMID- 2197021 TI - ACC/AHA guidelines for the early management of patients with acute myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (subcommittee to develop guidelines for the early management of patients with acute myocardial infarction). PMID- 2197022 TI - Role of the sympathetic nervous system in chronic heart failure. A historical and philosophical perspective. PMID- 2197023 TI - Myocardial catecholamines and the pathophysiology of heart failure. AB - The sympathetic nervous system contributes importantly to the clinical expression and, perhaps, to the course of myocardial failure. The failing heart exhibits both anatomic and functional defects in its sympathetic innervation and adrenergic receptor function. The nature of these abnormalities is at least partially dependent on the etiology of the underlying myocardial injury. Both efferent cardiac sympathetic tone and circulating catecholamines are elevated during the later stages of most forms of heart failure. This increase is not merely a reflex compensatory response but is also a reflection of defects in parasympathetic function, baroreceptor afferent nerve traffic, and regulation of sympathetic tone within the central nervous system through a serotonergic pathway. Prolonged stimulation of the heart may exhaust myocardial stores of norepinephrine and may lead to the destruction of sympathetic nerve terminals. Importantly, these abnormalities of autonomic function are distributed nonuniformly across the myocardium. Such heterogeneity can have profound effects on the temporal coordination of myocardial contraction and relaxation as well as the duration and configuration of the cardiac action potential and, thus, may contribute to both the mechanical and electrophysiological derangements seen in the failing heart. Therapy that makes sympathetic responses more uniform may improve the temporal coordination of excitation and contraction between innervated and denervated segments. This hypothesis might explain why both sympathetic agonists and antagonists may improve cardiac function since both types of drugs can restore the uniformity of neural stimulation. PMID- 2197024 TI - Sympathetic control of diastolic function in congestive heart failure. AB - Sympathetic cardiac stimulation is a major extrinsic compensatory mechanism that maintains or augments systolic and diastolic ventricular function during physiological stress or pathological conditions. In particular, catecholamines may selectively improve diastolic function by reducing myofilament calcium sensitivity, accelerating sequestration of calcium into the sarcoplasmic reticulum, and increasing the rate of actin-myosin cross-bridge turnover. These subcellular mechanisms, unique to inotropic agents that increase myocyte cyclic adenosine monophosphate, result in an increased rate and extent of ventricular relaxation and diastolic filling and a decrease in cardiac filling pressures. Despite these potentially favorable biochemical and mechanical actions, a number of limitations and theoretical concerns remain to be addressed before catecholamine therapy is widely administered to patients with congestive heart failure and diastolic dysfunction. PMID- 2197025 TI - The clinical challenge of Lyme disease. AB - Lyme disease is a systemic infection with protean clinical manifestations. In the past decade the disease has evolved from a medical curiosity to the most common vector-borne disease in the United States. The diverse clinical manifestations together with the lack of standardized serologic tests pose a significant diagnostic challenge for the practicing physician. The epidemiology, clinical presentation, diagnosis, and recommended therapy of Lyme borreliosis are reviewed. PMID- 2197026 TI - Proteolytic measurement of mitochondrial aspartate aminotransferase in human serum. AB - A new proteolytic measurement of serum mitochondrial aspartate aminotransferase was evaluated using cytosolic aspartate aminotransferase inactivating protease. Some of the proteases, such as, alpha-chymotrypsin, subtilisin and cytosolic aspartate aminotransferase inactivating protease 401 from Streptomyces species, also specifically inactivated cytosolic aspartate aminotransferase, but not mitochondrial, aspartate aminotransferase. The protease 401 was the most heat stable for storage and showed a higher inactivation rate for cytosolic aspartate aminotransferase--up to 7000 IU/L--more than 200-fold the upper limit. The coefficient of variation of the proteolytic method was less than 10%. Results by the present method correlated with those by the immunochemical method (r = 0.970) and the regression curve was Y = 0.95X + 1.60 (Y: immunochemical method; X: proteolytic method). In the present assay system, reference values for mitochondrial aspartate aminotransferase activity in 500 healthy people ranged from 2.0-7.2 U/L (mean 3.8 U/L). PMID- 2197027 TI - Pyruvate kinase deficiency. AB - Pyruvate kinase (PK) deficiency was initially described by Valentine et al. in 1961. Since then, more than 300 cases have been described, including 65 in Japan. PK deficiency is the most common hereditary nonspherocytic hemolytic anemia among several red cell enzyme defects of the Embden-Meyerhof glycolytic pathway. The clinical manifestations are highly variable. Splenectomy usually increases the hemoglobin level by about 2 g/100 mL. Standardization of methods for characterization of PK variants was achieved in 1979. There are four PK isozymes, M1, M2, L and R, in mammalian tissues. We have clarified the switch from M2-type to L-type PK during maturation of erythroid precursor cells. Recently we cloned and sequenced a full length human L-type PK cDNA. It will be useful to clarify the molecular basis of PK deficiency. PMID- 2197028 TI - The calcium signal and neutrophil activation. AB - The cytosolic free calcium concentration, [Ca2+]i in phagocytic cells (e.g. neutrophils, human leukemic cell line HL-60) is an important determinant of cellular activity. In resting phagocytes [Ca2+]i is low (approximately 100 nM), but in response to occupation of cell surface receptors, it rises to micromolar levels, thereby activating a variety of cellular functions. The increases in [Ca2+]i consist of two components: an immediate that is independent of extracellular Ca2+, and a more delayed that is abolished by the removal of extracellular Ca2+. These two components reflect the involvement of two subcellular structures in intracellular Ca2+ homeostasis: an intracellular Ca2+ store, referred to as the calciosome; and the plasma membrane. The function of the intracellular Ca2(+)-store depends on a Ca2(+)-pump, functionally and immunologically related to the cardiac sarcoplasmic reticulum Ca2(+)-ATPase, a Ca2(+)-storage protein, similar to muscle calsequestrin, and a Ca2(+)-release channel, which is sensitive to inositol 1,4,5-trisphosphate. The Ca2(+) regulatory function of the plasma membrane depends on a Ca2+ pump, similar to the erythrocyte-type Ca2(+)-ATPase, and a Ca2+ channel; the activity of the Ca2+ channel is closely coupled to phosphatidylinositol turnover. PMID- 2197030 TI - Biochemical and biological aspects of the plasminogen activation system. AB - Plasminogen activators (PAs) are specific proteolytic enzymes which convert the inactive proenzyme plasminogen to plasmin. The plasmin formed is a potent and nonspecific protease which cleaves blood fibrin clots and several other extracellular proteins. In addition to their primary role in the initiation of fibrinolysis, PAs are implicated in a variety of basic biological processes, such as, degradation of the extracellular matrix, tumor invasiveness, tissue remodelling, and cellular differentiation. This review describes recent observations on the biochemical and biophysical characteristics of the different components of the plasminogen activation system. This complex system includes: the proenzymes of tissue type PA (tPA) and urokinase type PA (uPA); the active enzymes tPA, uPA and plasmin; the substrate plasminogen; several natural inhibitors of PA and plasmin activity; and the cellular receptors that bind the proenzymes, enzymes, and inhibitor-enzyme complexes. Through the coordinated interactions of these components, the location, timing, and extent of potent proteolytic activity is controlled. Recent findings on the structure, properties, biological functions, and regulation of the different components of the plasminogen activation cascade are reviewed. Current methods for assay of the amount and activity of the enzymes, inhibitors, and receptors are described. Observations implying specific functions of the system in health and disease, and its potential utilization for diagnosis are examined. Specifically, the potential application of PAs as laboratory markers of neoplasia, as diagnostic tools in diseases of the blood clotting system, their use for monitoring of thrombolytic therapy, and their possible relevance in certain disease states are described. PMID- 2197029 TI - Alkaline phosphatase isozymes: recent progress. AB - The past few years have witnessed the reports of significant new events in alkaline phosphatase (AP) isozymes. The cloning of the relevant genes and their nucleotide sequencing have all been accomplished. As a group, the genes for the intestinal, germ cell and placental isozymes have considerable sequence similarity; it is noteworthy that they occupy vicinal positions on chromosome 2, while the tissue unspecific AP gene is located on chromosome 1. The latter makes evolutionary lineage and instances of coordinate expression understandable. Another new development is the demonstration of a phosphatidyl inositol glycan tail on the C-terminus of these chromosome-2 AP genes. This is the major membrane insertion mechanism for AP, which is a cell surface membrane enzyme. This information may be helpful in understanding the phenomenon of the depletion of intestinal mucosal AP during fat absorption. Finally, a discussion has been focussed on recent studies on seminoma and AP, including immunodetection and immunoradiotherapy. PMID- 2197031 TI - An evaluation of an enzyme immunoassay method for immunoreactive trypsin in dried blood spots. AB - A novel monoclonal antibody based enzyme immunoassay (EIA) method for the measurement of the human cationic trypsinogen (NeoScreen, AGEN Biomedical Ltd., Acacia Ridge, Australia) in dried blood spots for the neonatal screening of cystic fibrosis was evaluated. The calibration standards provided as dried blood spots by AGEN are highly unstable and must be replaced with user prepared materials. Reference values from control individuals were obtained by parametric methods. A preliminary comparison with a polyclonal antibody based RIA method (Trypsik, SORIN Biomedica, Saluggia, Italy) was performed. Regression analysis between the RIA and the EIA methods gave a coefficient of correlation of 0.58 for RIA values less than 40 micrograms/L and of 0.77 for RIA values greater than or equal to 40 micrograms/L. Average CV of the within-run imprecision for the EIA method was 19.6% and for the RIA method 28.8%. CVs of the between-run imprecision at low, intermediate and high values for the EIA method were 23.7%, 15.8%, 15.6% and for the RIA method 20.6%, 14.4%, 11.2%. The diagnostic accuracy analyzed by a Receiver Operating Characteristics (ROC) curve of the RIA method gave a maximum accuracy of 190.9 while that of a simulated ROC curve for the EIA method was 193.0. We found that the precision and the diagnostic accuracy of the EIA method (AGEN) are equal to or better than those of one of the RIA methods. PMID- 2197032 TI - Cytokines in disease. AB - Cytokines are peptides used by immune and inflammatory cells to communicate with each other and to control the milieu interieur in which they operate. Recent evidence suggests that they are of immense importance in controlling the local and systemic events of the immune response, inflammation, hemopoiesis, healing, and the systemic response to injury. Many of them can now be measured by immunoassay, and the role of such measurements in the diagnosis and management of disease is actively under investigation. Similarly, the availability of recombinant DNA techniques to produce cytokines in almost unlimited quantities is leading to new and exciting therapeutic applications. PMID- 2197033 TI - Development and performance of a highly sensitive and specific two-site immunometric assay of calcitonin gene-related peptide. AB - Calcitonin gene-related peptide (CGRP), a potent endogenous circulating vasodilator, is produced by the alternative splicing of the calcitonin/CGRP gene and is expressed mainly in neural and cardiovascular tissues. We recently reported a highly sensitive radioimmunoassay of CGRP, based on an antiserum recognizing the C-terminus of the molecule. We have also found that circulating immunoreactive CGRP is heterogeneous; thus we are unable to measure selectively the intact molecule with our one-site competitive approach. We therefore attempted to construct a two-site immunometric assay involving two antibodies, one that detects the C-terminus and another that recognizes the midregion of the molecule. To enhance assay sensitivity, we applied a colorimetric amplification system to this assay. This rapid, robust, and reproducible assay provides more nearly accurate estimates of circulating CGRP and offers a sensitive and more specific alternative to the radioimmunoassay, with advantages in speed, simplicity, and convenience. PMID- 2197034 TI - Two new two-step immunoassays for free thyroxin evaluated: solid-phase radioimmunoassay and time-resolved fluoroimmunoassay. AB - We measured concentrations of free thyroxin (FT4) in serum by using two new two step FT4 assays--a solid-phase two-step radioimmunoassay. Spectria, and a time resolved fluoroimmunoassay. Delfia--and compared the results with those by a two step FT4 assay (RIA-gnost), a one-step FT4 analog assay (Amerlex-M), and FT4 measured after equilibrium dialysis. The new FT4 assays classified 30 hypothyroid and 43 hyperthyroid patients (untreated) well. In 138 patients with nonthyroidal illness (NTI) and in late pregnancy (n = 36), fewer subnormal FT4 values were reported by Spectria (P less than 0.001), Delfia (P less than 0.001), and RIA gnost (P less than 0.01) than by Amerlex-M. The results of the Spectria and Delfia methods correlated with the results of the dialysis method (r = 0.76) in NTI patients and pregnancy, and were in better agreement with the clinical state than was FT4 by Amerlex-M. The FT4 values by Amerlex-M, but not by other methods, correlated with albumin concentration. We conclude that these new two-step methods present good alternatives for FT4 analysis. PMID- 2197035 TI - Discordant CA 125 measurements in normal healthy women. PMID- 2197036 TI - Irreproducible results. PMID- 2197038 TI - Cultural considerations in the treatment of Latinos with craniofacial malformations. AB - Latinos are expected to form the largest ethnic minority in the United States by the year 2000. Although there is considerable diversity within this group, a number of similarities prevail. Folk theories of etiology and treatment, family loyalties, attitudes toward health professionals, and hospitals appear similar across Latino subgroups. Successful treatment requires the knowledge and appreciation of cultural attitudes. PMID- 2197037 TI - Pharyngeal flap and facial growth. AB - The present study addressed two questions. Does the skeletal pattern of children with cleft lip and palate who require a pharyngeal flap differ from children with similar clefts who do not? Following a pharyngeal flap does the pattern of facial development change? Skeletal form prior to pharyngeal flap was compared using cephalograms in 52 subjects with unilateral cleft lip and palate (UCLP) who subsequently received a superiorly based pharyngeal flap and 52 UCLP controls matched for sex and age. The flap group had slightly smaller maxillary length and anterior face heights and greater mandibular protrusion (p less than 0.5) before the pharyngeal flaps were done. Preoperative and five year (minimum) postoperative records were analyzed for 29 early pharyngeal flap cases and 29 matched controls. Subsequent growth demonstrated some assimilation of the flap group with the controls, but repeated measures analysis of variance failed to identify any important differences in growth after pharyngeal flap, suggesting that the superiorly based pharyngeal flap carries no systematic risk of interference with facial growth. PMID- 2197039 TI - Cultural considerations in the treatment of craniofacial malformations in African Americans. AB - African Americans represent the second largest ethnic group in the United States. Even though there are mixtures of other races and cultures, their primary ancestry is African. Because of their heritage and cultural practices in the United States, the acceptance of the diagnosis and treatment of craniofacial anomalies is different from that of other groups. Positive aspects of the culture that augment the treatment of disorders include the strength of the family and a strong religious belief system. Factors that may impede the effectiveness of clinical intervention are economics and accessibility to medical care. PMID- 2197040 TI - Asian-American cultural perspectives on birth defects: focus on cleft palate. AB - The treatment of birth defects and other disabilities is influenced by cultural beliefs of the individual, family and society. The recent influx of Asian/Pacific immigrants and refugees has challenged professionals to provide appropriate services to individuals with cleft palate and their families from these populations. The issues of folk and religious beliefs are complex, and the variations among them are often intertwined. Their comprehension is important because studies have reported a higher incidence of cleft lip and/or palate among Asian/Pacific populations. Successful communication with Asian individuals requires recognition and consideration of cultural diversity and differing interactional styles. PMID- 2197041 TI - Feedforward and feedback control mechanisms in the gut. With special emphasis on inhibitory feedback by nutrients in the distal small bowel and colon. PMID- 2197042 TI - Idiopathic retroperitoneal fibrosis--an update. AB - Our belief in a non-operative approach to the management of RPF hinges on the differential diagnosis; the closer the approach to the certainty in establishing the diagnosis, the less is the risk of error in medical treatment. Careful history taking and intelligent use of the available range of investigations should allow near certainty in diagnostic accuracy and thus the progression to non-operative management in most patients. The cause of RPF remains obscure, further research into the possibility of an auto-immune reaction, perhaps a response to some factor introduced in the latter half of this century would seem to offer most prospect of success. PMID- 2197043 TI - Obstruction of the hepatic veins. PMID- 2197044 TI - Stomas in colorectal surgery: options and alternatives. PMID- 2197045 TI - Is macrophage death on the field of battle essential to victory, or a tactical weakness in immunity against tuberculosis? PMID- 2197046 TI - Beneficial effects of the thymic hormone preparation thymostimulin in patients with defects in cell-mediated immunity and chronic purulent rhinosinusitis. A double-blind cross-over trial on improvements in monocyte polarization and clinical effects. AB - Twenty patients with chronic purulent rhinosinusitis were treated with TP-1 (Serono; 1 mg/kg body weight), in a double-blind cross-over trial. TP-1 was administered by daily i.m. injections for the first 14 days followed by two injections/week for 6 further weeks. The patients were immunologically special in that they had defects in their cell-mediated immune system. Fourteen showed a decreased chemotactic responsiveness of their peripheral blood monocytes as measured in the polarization assay. This defective function can probably be ascribed to the presence in serum of low molecular weight factors (LMWFs; less than 25 kD). As reported earlier, this factor shows a structural homology to the envelope protein of murine and feline leukaemia virus (P15E). Thirteen patients showed a defective delayed-type hypersensitivity (DTH) skin test reactivity towards candidin and/or streptokinase-streptodornase (Sk/Sd) antigen, 14 had a defective MIF production from their peripheral blood lymphocytes towards candidin, Sk/Sd and/or Haemophilus influenzae antigen. Eighteen patients completed the TP-1 trial and showed clinical improvements: 12 out of 15 were feeling better during TP-1 therapy and the nasal mucosa showed on inspection absent mucopurulent secretion in 13 patients. Positive bacterial culture rates for the nose decreased from 14 out of 16 to five out of 15. Placebo treatment had no significant effects. The clinical improvements were accompanied by a better performance of the cell-mediated immune system; the most significant effects were recorded in the monocyte polarization assay. The suppressive P15E-like LMWFs in serum clearly decreased during TP-1 treatment. In vitro TP-1 neutralized the immunosuppressive effect of the LMWFs. The restoring effects of TP-1 on monocyte polarization and its neutralizing activity of P15E-like LMWFs could explain the beneficial effects of thymic hormone treatment reported in adults with clinical signs of immunodeficiency in the presence of a full T cell repertoire. PMID- 2197047 TI - Strain differences in mouse cellular responses to Mycobacterium lepraemurium and BCG subcutaneous infections. I. Analysis of cell surface phenotype in local granulomas. AB - C57BL/6, BALB/c and CBA mice were subcutaneously infected with either Mycobacterium lepraemurium (MLM) or BCG, and studied for bacillary growth, granuloma size of infected footpads and draining lymph nodes (DLN), and DLN cell surface phenotype. Whereas, BCG-infected mice controlled the infection and developed early and large granulomas, MLM-infected mice exhibited major strain variations in their resistance to the infection, as well as in the granuloma size and kinetics. C57BL/6 mice, highly resistant, displayed early and regressive granulomas; BALB/c mice showed lower resistance and early granulomas that grew continuously; CBA mice, highly susceptible, developed late, soft, phagocyte-rich granulomas. Important strain differences in lymph node lymphocyte subset distribution could be observed prior to any infection: C57BL/6 mice displayed higher B cell percentages than both of the other strains and BALB/c mice showed the highest CD4/CD8 ratios, followed by CBA and C57BL/6 mice. BCG and MLM infections both induced similar changes of these parameters in all three strains: that is a decrease of the B cell percentage and a decrease of the CD4/CD8 ratio, and the strain differences observed in uninfected mice persisted. On the other hand, DLN cells stimulated by the infecting bacillus and interleukin 2 also displayed an increase of the CD8 T cell percentage as compared with normal lymph node cells, but this phenomenon was much less pronounced in BALB/c mice, whether infected by MLM or BCG, and in MLM-infected CBA mice, than in BCG- or MLM infected C57BL/6 (B6) mice. Thus the ability of C57BL/6 mice to generate an early and persistent CD8 T cell response to mycobacteria may contribute to their resistance to MLM. PMID- 2197048 TI - The effects of recombinant granulocyte-macrophage colony-stimulating factor (GM CSF) and interleukin-3 on the secretory capacity of human blood eosinophils. AB - The effects of recombinant human GM-CSF and interleukin-3 (IL-3) on human blood eosinophil survival, activation, and secretion were studied. Purified normal density eosinophils from patients with the idiopathic hypereosinophilic syndrome (HES) survived in culture for 7 days (50% viable) in the presence of 50 nM GM-CSF or 50 nM IL-3. Neutrophils did not survive after 4 days. No eosinophils survived in the absence of GM-CSF or IL-3. In two out of five patients studied, the cultured eosinophils became elongated with numerous processes. In all five patients the cells became adherent, but there were no morphological signs of degranulation. Both GM-CSF and IL-3 activated eosinophils, transforming the storage form of eosinophil cationic protein (ECP) into the secreted form. The proportion of activated cells increased from less than 20% to over 50% after 4 days in culture. However, GM-CSF and IL-3 did not induce secretion on their own. On the other hand, when GM-CSF/IL-3-activated eosinophils were exposed to known secretory stimuli, there was a six-fold increase in the amount of ECP released when the cells were stimulated with sepharose coated with C3b, and a two-fold increase when they were stimulated with sepharose-activated whole autologous serum. Eosinophils from patients taking steroids were unable to secrete their granule contents, even though they became activated by GM-CSF and IL-3. A novel finding was that sepharose-activated whole serum was an extremely potent secretory signal for ECP, releasing up to 50% of the total ECP content. These studies showed that GM-CSF and IL-3 prime eosinophil effector function by initiating granule solubilization which is the first step in the secretory event, without affecting the subsequent extracellular release of granule proteins. PMID- 2197049 TI - Macrophage heterogeneity in human fetal tissue. Fetal macrophages. AB - The immunophenotype of the macrophage population in human fetal tissue was studied, using a panel of monoclonal antibodies against cells of the macrophage/monocyte lineage. Using a double-labelling technique two main populations were observed in tissue from 14 weeks of estimated gestational age (EGA); EBM11+ DR+ and EBM11+ DR- cells of which a small proportion were also RFD7+. Most macrophages were negative with 3.9, an antibody specific for the adhesion molecule P150.95 and LP9 which is specific for a lysosomal enzyme. The exception to this was a small population of positive cells in the thymus. Small numbers of 3.9+ cells were also infrequently observed in tissue at and above 17 weeks of EGA, while occasional RFD9+ cells were only observed in most tissues, before this time. The higher percentage of macrophages were DR+ DQ- DP-, with a few DQ+ cells appearing at 15 weeks of EGA. In the thymus, DQ+ cells outnumbered DP+ cells especially in the medulla. These results indicate the heterogeneous and immature nature of the fetal macrophage population and point to the importance of age, tissue-specific factors and probable immune mediators in macrophage differentiation. PMID- 2197050 TI - Pharmacokinetics of drug overdose. AB - Drugs ingested in overdose can have altered pharmacokinetics of absorption, distribution, and elimination. The pathophysiologic consequences of overdose can also change a drug's pharmacokinetic properties. Many toxicologic interventions are based on modifying the drug's pharmacokinetics (e.g., impairing absorption or enhancing elimination). Serum drug monitoring, even with its limitations, does have a role in managing the patient who has taken an overdose. PMID- 2197051 TI - Mechanisms of toxic cell injury. AB - The biochemical mechanisms by which xenobiotic agents initiate cell injury involve networks of interactions at a variety of molecular and structural targets. The author highlights current concepts in six major areas of investigation: covalent binding, oxidative stress, alterations of glutathione and protein thiols, peroxidation and hydrolysis of phospholipids, mitochondrial deenergization, and alterations of intracellular calcium homeostasis. PMID- 2197052 TI - Nephrotoxic and ototoxic agents. AB - It is well established that many drugs, such as the aminoglycoside antibiotics and the chemotherapeutic drug cisplatin, are capable of inducing both nephrotoxicity and ototoxicity. The factors that selectively predispose the kidney and inner ear to the toxic effects of these agents as well as the mechanism by which damage is produced are not well defined. The two organs differ greatly in their exposure to these toxic agents. The kidney has an abundant vascular supply and tends to selectively concentrate a number of drugs within the renal cortex or medulla, often to toxic levels. The vascular supply of the inner ear is not as extensive. In addition, the stria vascularis of the cochlea may act as a functional regulator of drug entry into inner ear fluids. The absorption of drugs into perilymph and endolymph is poorly understood. Selective accumulation theories of drug accumulation in the inner ear must be questioned because of the results of recent pharmacokinetic studies, which give contrary data. Drug-induced ototoxicity and nephrotoxicity can be explained on a cellular level. Studies using radiolabeled gentamicin suggest that binding mechanisms of the drug to the plasma membrane of the outer hair cells of the cochlea and vestibular apparatus and to the brush border receptors of the renal proximal convoluted tubules are similar. This suggests the same receptor sites for aminoglycosides occur in otic and renal organs. Calcium channels are implicated because of the reversibility of aminoglycoside-induced changes in the cochlear microphonic by calcium and other divalent cations. Calcium channel blockers, such as verapamil, reduce the nephrotoxicity of a number of drugs that are also ototoxic. Studies are needed to assess potential prevention of ototoxicity by use of these same calcium channel blocking agents. Aminoglycosides concentrate within the lysosomes of renal proximal tubular cells. Possibly, they also may concentrate in lysosomes within the cells of cochlear and vestibular structures. Nephrotoxic heavy metals concentrate within proximal tubular cells and, some, such as lead or bismuth, specifically concentrate within intracytoplasmic or intranuclear inclusion bodies. Studies are necessary to determine if the same metals accumulate within the cochlear and vestibular cells, inclusion bodies, or both. These questions and others must be answered before it can be determined why many nephrotoxic drugs and agents are also ototoxic. PMID- 2197053 TI - Alcohol. AB - Ethyl alcohol is readily available and is, therefore, a frequent cause of poisoning. Alcohol is also an important substance of abuse. The author discusses the approaches to medicolegal alcohol determinations. The pharmacokinetics of alcohol are explained, and ramifications for substance abuse testing are examined. PMID- 2197054 TI - Clinical toxicology of drugs used in the treatment of opiate dependency. AB - Many aspects of the pharmacokinetics of methadone have been evaluated since 1970. Analytic techniques used to monitor urine and serum or plasma concentrations of methadone and its metabolites have improved with advances in chromatography and development of immunoassay techniques. On reviewing the literature on methadone since 1970, however, there were several recurring limitations of the experimental design in a large number of the studies reported. These include: 1. No appreciation for the effect of urinary pH on excretion of methadone 2. Small number of patients enrolled with inadequate control subjects 3. The effect of smoking cigarettes was not evaluated or adequately controlled 4. Urine collections were often obtained without supervision and correcting results to creatinine excretion 5. Blood specimens were generally not collected from 0-15 minutes after intravenous dosing 6. Incomplete excretion data (nonhydrolysis of glucuronide conjugates) in the urine 7. Most studies did not evaluate protein binding of methadone when attempting to correlate therapeutic control or failure with serum concentrations of methadone. In general, the literature supporting the use of naltrexone was more favorable than for methadone, buprenorphine, LAAM, and clonidine. The major limitation on the use of naltrexone, however, is the lack of incentive for the patient to keep taking the medication. If the use of naltrexone, LAAM, buprenorphine, or clonidine becomes widely available, robust analytic techniques must be developed for monitoring of these drugs, their metabolites, or both in the urine to verify patient compliance. PMID- 2197056 TI - Technical aspects of quantification of aluminum. AB - Aluminum has been implicated as a contributing factor to dialysis encephalopathy syndrome (DES) and osteomalacic osteodystrophy. Monitoring of its level together with i-PTH, desferoxamine infusion test, or bone biopsy gives the degree of intoxication. Specimens for aluminum must be collected in containers washed in nitric acid or disodium EDTA to avoid contamination. Determination is made with flameless atomic absorption spectrometry or neutron activation. Various experimental conditions for the former together with discussion on their merits and shortcomings are given. Included are protein precipitation, matrix modification, background correction, and sampling technique. PMID- 2197055 TI - Aspects of aluminum toxicity. AB - Aluminum is the most abundant metal in the earth's crust. The widespread occurrence of aluminum, both in the environment and in foodstuffs, makes it virtually impossible for man to avoid exposure to this metal ion. Attention was first drawn to the potential role of aluminum as a toxic metal over 50 years ago, but was dismissed as a toxic agent as recently as 15 years ago. The accumulation of aluminum, in some patients with chronic renal failure, is associated with the development of toxic phenomena; dialysis encephalopathy, osteomalacic dialysis osteodystrophy, and an anemia. Aluminum accumulation also occurs in patients who are not on dialysis, predominantly infants and children with immature or impaired renal function. Aluminum has also been implicated as a toxic agent in the etiology of Alzheimer's disease, Guamiam amyotrophic lateral sclerosis, and parkinsonism-dementia. PMID- 2197057 TI - The management of myocardial infarction: an update. PMID- 2197058 TI - Techniques and applications of Doppler echocardiography. PMID- 2197059 TI - Diagnosis and management of patients with asymptomatic carotid artery bruit. AB - Asymptomatic lesions cause approximately 150,000 strokes in the U.S. each year. Lesions associated with significant risk of stroke include atherosclerotic plaques of the carotid bifurcation that compromise the lumen of the internal carotid artery by 75% or more, particularly if the plaque consists of soft material. A group of individuals with significant risk are those with atherosclerotic plaques containing large ulcerations. The risk of carotid endarterectomy is lower for patients with critical lesions that are asymptomatic than for patients with any other surgical indication, and averages a combined risk of morbidity and mortality of less than 1%. Two randomized, prospective studies are currently underway to compare the risks and the benefits of medical and of surgical management of this disease. Until the results of the randomized studies are available, prophylactic carotid endarterectomy for critical lesions is justified if the risk of surgery in the hands of an individual surgeon is less than 3% combined morbidity and mortality. PMID- 2197060 TI - Incidence of listeriosis in Connecticut. AB - In Connecticut, 92 cases of human listeriosis were reported to the Department of Health Services from 1984 to 1988. The annual incidence per million population ranged from 7.3 in 1984 to 4.2 in 1988. The average annual incidence was 5.6 per million population. Case rates were highest in those aged 70 years and older (15.8 per million). Cases included 12 pregnant women and 11 newborns. Bacterial meningitis was the primary diagnosis in 23 cases. Of the 49 isolates of Listeria monocytogenes that were serotyped, 21 (43%) were type 4, 24 (49%) were type 1, and 4 (8%) were nontypable. PMID- 2197061 TI - Illicit price of cocaine in two eras: 1908-14 and 1982-89. PMID- 2197062 TI - The magic mountain. PMID- 2197063 TI - Update on topical cyclosporin A. Background, immunology, and pharmacology. AB - Systemic cyclosporin A (CsA) is currently being used for immunosuppression in solid organ transplantation. Its unique mechanism of action and low myelotoxicity have vastly improved the prognosis for patient survival. A reversible and irreversible nephrotoxicity has complicated its use. CsA works via the inhibition of both lymphokine release and subsequent activation of cytotoxic T cells. The corneal allograft model presents several unique features that make it amenable to local immunosuppressant therapy. Following topical application, CsA corneal levels have been obtained above the experimentally determined levels necessary for local immunosuppression. CsA represents one of a new class of specific, potent immunomodulators, which may improve the prognosis for patients at high risk for allograft rejection. PMID- 2197064 TI - Liver transplantation: a 31-year perspective. Part I. PMID- 2197065 TI - Prostate cancer. PMID- 2197067 TI - The mas oncogene as a neural peptide receptor: expression, regulation and mechanism of action. AB - The human mas oncogene, which renders transfected NIH/3T3 cells tumorigenic, was identified as a subtype of angiotensin receptor by transient expression in Xenopus oocytes and stable expression in the mammalian neuronal cell line, NG115 401L. The mas receptor preferentially recognizes angiotensin III, and is expressed at high levels in brain. The mas/angiotensin receptor functions through the breakdown of inositol lipids and can drive DNA synthesis, unlike another inositol-linked peptide receptor, that for bradykinin. Comparative analysis of several early biochemical events elicited by either angiotensin or bradykinin stimulation of mas-transfected cells has not indicated a specific difference correlated with mitogenic activity. In particular, the inositol lipid kinase, phosphatidylinositol-3-kinase, thought to be involved in the mitogenic mechanism of platelet-derived growth factor receptors, is unaffected by activation of mas. These results have shown that a proto-oncogene encodes a neural peptide receptor, indicating that peptide receptors may be involved in differentiation and proliferation processes, as are other identified proto-oncogenes. PMID- 2197066 TI - Controls of cell proliferation in yeast and animals. AB - Genetic studies using fission yeast (Schizosaccharomyces pombe) have identified a gene, cdc2, whose product (p34cdc2) is a protein kinase required for traversal of both the G1 and G2 cell cycle control points. Genetic complementation has been used to demonstrate that p34cdc2 homologues are functionally and structurally conserved in distantly related eukaryotes, and p34cdc2-related proteins are components of both maturation-promoting factor (MPF) and the M phase (growth associated) histone H1 kinase. The p34cdc2 homologues of multicellular eukaryotes undergo potentially regulatory phosphorylation changes through the cell cycle. Phosphorylation on serine during late G1 is accompanied by a significant increase in p34cdc2 kinase activity which, by analogy with fission yeast, may betray a function related to control over entry into S phase. Phosphorylation on threonine and tyrosine in G2 precedes dephosphorylation of these residues during kinase hyperactivation and entry into mitosis. In addition, long-term control of expression of mammalian p34cdc2 homologues is likely to be exerted at the transcriptional level. These observations provide the framework of a universal model for the control of eukaryotic cell proliferation, in which the p34cdc2 protein kinase integrates multiple cues to signal the initiation of S phase and, subsequently, mitosis. PMID- 2197068 TI - Acute respiratory distress syndrome (ARDS). AB - The acute respiratory distress syndrome (ARDS) is a common clinical catastrophe following acute lung injury. A multiplicity of clinical states can lead to ARDS. A new classification system has been proposed to deal with associated organ system failure and varying degrees of acute lung injury. ARDS is a permeability and inflammatory edema with damage and destruction at the air blood interface. Many cellular and humoral mediators probably attack the lung's surfactant system which in turn enhances edema formation. Supportive care with mechanical ventilation and positive end expiratory pressure results with the salvage of less than 50% of patients. Lung regeneration requires weeks or months to become complete in those who survive. Thus far no individual pharmacological agents have been shown to alter prognosis. Controlled clinical trials are required to evaluate new and older pharmacological agents alone or in combination, and surfactant replacement. PMID- 2197069 TI - [Intrarectal ultrasonography in the preoperative assessment of the depth of infiltration of rectal tumors]. AB - From June 1987 to February 1990, 142 out of 319 patients with rectal tumours were investigated by ultrasound scanning with the object of ascertaining the depth to which the tumour had infiltrated. This examination proved completely feasible in 130 of these patients (84 men, 46 women, mean age 61.7 [42-84] years). Postoperative histological examination revealed an adenoma (n = 59) or a T1 carcinoma (n = 19), while intrarectal ultrasonography disclosed the same findings in 79 patients (true-positive in 75 cases). A T2-tumour was diagnosed by histological examination in 24 patients, and by ultrasonography in 22 (true positive in 18 cases). The histological diagnosis of a tumour in stage T3 or T4 (n = 27) was in close agreement with the ultrasound findings (n = 24). The positive predictive value of ultrasonography ranged between 0.94 and 0.97 depending on the staging of the tumour, and the sensitivity between 0.75 and 0.96. Preoperative ultrasonographic determination of the depth of invasion of a rectal tumour enables the surgeon to devise a therapeutic plan to suit the individual patient's needs; one option may be local excision. PMID- 2197070 TI - [Recommendations for the treatment of infectious endocarditis]. PMID- 2197071 TI - [Treatment of Behcet's syndrome with azathioprine]. PMID- 2197072 TI - Appetite disturbance and the problems of overweight. AB - During the past 50 years, obesity has increasingly become a problem in Western societies. If low energy output by these individuals (i.e. lack of exercise) cannot be held totally accountable for this problem, then their energy input (i.e. appetite) must play a significant role. There are many elements that give rise to appetite disturbances and their effects on weight gain, weight loss or its maintenance. Previously, it was thought that emotional disturbances led to overeating and overweight; a theory that was supplanted later by the theory that physiological rather than psychological causes were to blame. Today, it is generally believed that appetite is controlled by the interaction of internal (genetic, physiological and chemical) and external (environmental and psychosocial) processes. The role of nutritional and dietary factors in controlling the expression of appetite are particularly important. Thus, appetite (hyperphagia or increased hunger) can be induced by changes in brain neurotransmitters and neuromodulators, altered liver metabolism, adjustments of the nutrient/sensory components of the diet, environmentally applied stressors, the mental and behavioural imposition of dieting and the administration of various psychotropic medications. This review focuses on the role of each of these mechanisms plays in the genesis and maintenance of appetite disturbances; the conclusion of each of these contributions is the same--control of appetite must be achieved in order to treat obesity, and to do this, control must be exerted via regulation of the food supply, cognitive methods, environmental adjustment or by pharmacological tools. PMID- 2197073 TI - Management strategies for weight control. Eating, exercise and behaviour. AB - Obesity is a major health and social problem worldwide for which no single satisfactory treatment exists. Because of the prevalence of the disease, numerous therapeutic strategies have been attempted--often unsuccessfully. Weight loss programmes based on dietary restriction of caloric intake and nutritional education, exercise, surgical (gastroplasty, gastric bypass) and procedural (gastric balloon, waist cord, jaw wiring, liposuction) intervention and pharmacotherapy (appetite suppressants, thermogenic agents, bulking agents) used alone or in combination, have produced weight loss in the short to medium term; however, weight is generally regained on discontinuation of treatment. Behaviour modification programmes appear to offer the highest success rate in the long term. Weight loss is not rapid, although losses of 10 to 15 kg have been achieved after 6 months, and this may be increased when behaviour modification therapy is combined with more aggressive treatments such as severe caloric restriction or jaw wiring. Behaviour modification is particularly beneficial in special patient groups such as the obese elderly, children or adolescents, and disabled patients. Thus, although it appears that each of the treatments developed for the management of obese patients has its place, the cornerstone of therapy for most patients remains a programme of dietary restriction, combined with exercise and behaviour modification. PMID- 2197075 TI - Carbohydrate craving. Relationship between carbohydrate intake and disorders of mood. AB - Common to repetitive episodes of weight gain or failures to succeed on weight loss regimens is the excessive consumption of carbohydrate-rich foods in association with dysphoria. The brain neurotransmitter, serotonin, seems to be involved in the abnormal regulation of mood and food intake that underlies diet failures or weight gain in individuals who suffer from carbohydrate craving obesity (CCO), premenstrual syndrome (PMS) and seasonal affective disorder (SAD). All 3 syndromes are characterized by episodic bouts of increased carbohydrate consumption and depressed mood. Studies with dietary treatment or drugs that enhance serotoninergic neurotransmission have found that increased serotonin neurotransmission is associated with normalised food intake and mood. These results suggest that periodic intervention with dietary or drug treatment that increases serotonin availability may help sustain weight or assist in weight loss. PMID- 2197074 TI - The role of serotonin in eating disorders. AB - Recent pharmacological studies have more precisely characterised the nature of the inhibitory effect of brain serotonin (5-hydroxytryptamine) on feeding behaviour. Thus, the brain sites and receptors involved have been identified, and a possible physiological role of endogenous serotonin in controlling natural patterns of eating and nutrient selection has been defined. The medial hypothalamus is believed to be a critical location in the mediation of serotonin's action. Specifically, the paraventricular and ventromedial nuclei are known to be involved in controlling energy balance, while the suprachiasmatic nucleus determines circadian patterns of eating. Serotonergic stimulation of these 3 nuclei with exogenous serotonin or drugs that release endogenous serotonin, preferentially reduces carbohydrate intake in naturally feeding animals through satiety mechanisms involved in the termination of feeding. This phenomenon is mediated by serotonin and possibly serotonin receptors, in contrast to serotonin autoreceptors which potentiate feeding possibly by inhibiting serotonin release. The activity of serotonergic function in the medial hypothalamus exhibits a circadian rhythm which is characterised by a peak at the beginning of the active cycle when the motivation to eat is strongest and is triggered by deficits in energy stores. At this time, carbohydrate is found to be the naturally preferred macronutrient, and it appears that serotonin becomes most activated under these conditions to terminate the carbohydrate-rich meal, possibly by activating satiety neurons localised in the medial hypothalamus. In this process, serotonin may interact antagonistically with noradrenaline (norepinephrine) and its alpha 2-noradrenergic receptors that normally function to enhance carbohydrate intake at the onset of the natural feeding cycle. Moreover, while inducing satiety for carbohydrate, serotonin may also play a role in switching the animal's preference towards protein. The regulation of this macronutrient is closely linked to that of carbohydrate, and it is normally preferred in the second meal of the natural feeding cycle. Most of the pharmacological evidence to date generally supports the hypothesis that disturbances in serotonin function occur in eating disorders. Decreases in plasma tryptophan, urinary 5-hydroxyindoleacetic acid (5-HIAA), platelet serotonin binding and basal cerebrospinal fluid 5-HIAA in anorexia nervosa normalise upon weight restoration and appear to be starvation effects. These alterations in serotonergic function may however perpetuate the symptomatology of anorexia nervosa once the illness is set in motion. Some drugs which in part affect serotonergic function facilitate weight gain in conjunction with an integrated psychotherapeutic and behavioural programme. Patients with bulimia nervosa, regardless of the presence of anorexia nervosa or major depression, who have been relatively weight stable and free of binge/vomit episodes for at least 3 weeks, have significantly blunted prolactin responses to the serotonin agonists. These findings indicate that post-synaptic responsiveness in hypothalamic-pituitary serotonergic pathways is reduced in bulimia. Similar alterations in other serotonin pathways at or above the level of the hypothalamus may contribute to binge eating and other behavioural symptoms in bulimic patients. The clinical response to several psychotropic agents known to potentiate serotonergic transmission further substantiates a serotonin dysregulation hypothesis of bulimia nervosa.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2197077 TI - Regulation and adaptation at the molecular level. PMID- 2197076 TI - Dexfenfluramine. Its place in weight control. AB - Dexfenfluramine, the dextrostereoisomer of fenfluramine, is a pure serotonin (5 hydroxytryptamine) agonist, apparently devoid of any additional antidopaminergic or sympathomimetic effects. The drug is approximately twice as effective as its racemic predecessor in reducing food intake in animals, and at a dose of 30 mg/day dexfenfluramine substantially modifies eating behaviour in man. Thus, a reduction in the motivation to eat and fewer snacking episodes were seen in volunteers treated with the drug, while total caloric and carbohydrate (but not protein) intakes were reduced in obese carbohydrate cravers. In clinical studies in obesity, dexfenfluramine combined with dietary support has produced mean weight reductions superior to those achieved with placebo over 3-month treatment periods. Importantly, the drug appears to maintain its weight-reducing effects for at least 12 months, without serious adverse effects. Dexfenfluramine appears to possess many of the properties of an 'ideal' pharmacotherapeutic agent for obesity. However, further long term clinical studies are required to confirm the promising efficacy and safety data obtained to date, and to further define the most appropriate indications for its use. Ideally, the drug should be used as adjunctive treatment in the clinical management of more severe cases of obesity, which are refractory to simpler supportive measures such as dietary or psychological counseling. PMID- 2197078 TI - Gonadotropin-releasing hormone messenger ribonucleic acid levels are unaltered with changes in the gonadal hormone milieu of the adult male rat. AB - Testicular function is regulated by the negative feedback effect of sex hormones acting at the brain and pituitary to inhibit the secretion of LH and FSH. An important component of this feedback axis is presumed to involve regulation of secretion and possibly synthesis of GnRH by the brain. We tested the hypothesis that the castration-induced increase in gonadotropin secretion is subserved, at least in part, by increased synthesis of GnRH. Using in situ hybridization and an oligonucleotide probe to pro-GnRH messenger RNA (GnRH mRNA), we compared the level of cellular GnRH mRNA and the relative number of GnRH mRNA-containing neurons between intact and 21-day castrate adult male rats. To derive estimates of the number of GnRH cells and the cellular GnRH mRNA content, coronal sections from each animal were anatomically matched between intact and castrate groups. All identifiable cells within these sections were counted and analyzed with the aid of a computerized image analysis system, by an observer unaware of the animal's experimental group and were assigned an anatomical location for reference. In an initial experiment, we observed no difference in cellular GnRH mRNA signal level between intact (n = 4) and castrate (n = 5) animals (129 +/- 8 vs. 139 +/- 5 grains per cell); however, we did find a statistical difference between the intact and castrated groups in the relative number of GnRH mRNA containing cells (intact: 212 +/- 15 vs. castrate: 320 +/- 18). To confirm this observation, we repeated the experiment by again comparing the number of GnRH mRNA-positive cells between intact (n = 4) and castrate (n = 4) rats. In this second experiment, we found no difference in the number of identifiable GnRH mRNA containing cells between intact and castrate animals (272 +/- 14 vs. 274 +/- 36, respectively); this was the case for the total cell count as well as when the data were analyzed by anatomical region. To clarify the conflicting results on cell counts of Exps 1 and 2, we repeated the experiment a third time, again comparing both the number of GnRH mRNA-containing cells and the cellular content of GnRH mRNA. In this experiment, we observed that neither cell number nor content of GnRH mRNA differed between the intact and castrate groups. Again, this was the case for total cell count, as well as when the data were analyzed by anatomical region.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2197079 TI - A modulatory role for luteinizing hormone-releasing hormone in nociceptive responses of female rats. AB - We have shown that responsiveness to noxious stimuli change after gonadal steroid treatment and during the estrous cycle. In the present study, we evaluate the role of LHRH in modulating nociceptive responses in female rats. In ovariectomized (OVX) rats, an LHRH agonist ([ Des-Gly10] LHRH ethyl amide; 1 ng/rat/microliters), given intraventricularly (icv) at either 90, 60, or 30 min before a hot-plate test caused a time-dependent, significant increase in sensitivity to the noxious thermal stimulus (hyperalgesia) vs. saline-treated controls. Further, the LHRH agonist (1 ng/rat/microliters; icv) attenuated morphine (5 mg/kg, sc)-induced antinociception. The injection of an LHRH antagonist, [D-Phe2,Pro3,D-Phe6] LHRH, to OVX rats in doses of 0.1, 1, or 10 ng/rat 30 min prior to morphine, enhanced and prolonged morphine-induced antinociception in a dose-dependent manner. Moreover, the hyperalgesia observed in OVX rats treated with naloxone (1 mg/kg, sc) was reversed by preinjection of either the LHRH antagonist (0.1 ng/rat, icv) or LHRH antiserum. OVX rats primed with estradiol benzoate (EB) and progesterone (P) were less sensitive to the antinociceptive effect of morphine than OVX rats. When EBP-treated rats received the LHRH antagonist prior to morphine, a twofold increase in morphine-induced antinociception was observed. A similar effect was observed in EBP-treated rats after the injection of LHRH antiserum. In conclusion, LHRH may interact with central opioid systems causing an increased sensitivity to nociceptive stimulation (hyperalgesia) and reduction of the antinociceptive effect of morphine. PMID- 2197080 TI - Unexpected inhibitory action of N-methyl-D,L-aspartate or luteinizing hormone release in adult ovariectomized rhesus monkeys: a role of the hypothalamic adrenal axis. AB - N-methyl-D,L,-aspartate (NMA), an analog of the excitatory neurotransmitter aspartate, has been previously shown to acutely stimulate LH release in the rodent and primate. In this study, we examine the effect of NMA on LH secretion in the long term ovariectomized adult rhesus monkey. After a 3-h control period, three successive iv bolus injections of NMA (10 or 45 mg) were administered at hourly intervals, and LH and cortisol responses were compared with those after iv administration of physiological saline. LH concentrations remained unchanged throughout the saline infusion (n = 6) and during the 10-mg NMA injection regimen (n = 5). Unexpectedly, LH decreased during NMA injections at a dose of 45 mg (n = 10): areas under the LH curve, expressed as percentage of baseline control, were: hour 1, -16.0% (+/- 2.7 SE); hour 2, -28.4 (+/- 3.2 SE); hour 3; -30.9 (+/- 3.2 SE), P less than 0.005 vs. saline or 10 mg NMA. This inhibitory effect of NMA was prevented by the coadministration of GnRH (3 micrograms) (n = 5), suggesting that NMA acts at a suprapituitary level. Cortisol secretion was significantly increased by 45 mg of NMA; Total areas under the cortisol curve, expressed as percentage of baseline control, were: saline, -24.2% (+/- 4.2 SE); NMA (10 mg), 24.2 (+/- 2.0); NMA (45 mg), +22.2 (+/- 6.2); P less than 0.001 vs. NMA (10 mg) and saline, suggesting that NMA at the higher dose may activate the adrenal axis. To examine a possible role of the adrenal axis on NMA-induced LH inhibition, we next examined the effects of intraventricular administration of antiserum to CRF. Pretreatment with CRF antiserum prevented the decrease in LH levels seen during NMA (45 mg) in 4 of 8 monkeys (hour 2, -8.5% (+/- 6.5); hour 3, -10.3% (+/- 4.3); P less than 0.01 vs. NMA). The NMA-induced cortisol increase was prevented in the antiserum responsive but not in the nonresponsive animals. A similar preventive action on LH was seen after administration of the endogenous opiate receptor antagonist naloxone (2 or 5 mg/h), most notably in caged animals (n = 4: hour 1, 6.2% (+/- 3.8); hour 2, -2.8 (+/- 4.0); hour 3, -9.9 (+/- 5.0); P less than 0.005 vs. NMA, 45 mg, for hour 1 and hour 2). We conclude that the unexpected inhibitory effects of NMA on LH secretion in the adult ovariectomized monkey are the result of the activation of the hypothalamic-pituitary-adrenal axis by NMA and specifically of the release of CRF and endogenous opioid peptides. PMID- 2197081 TI - Rapid augmentation by progesterone of agonist-stimulated luteinizing hormone secretion by cultured pituitary cells. AB - Progesterone acts bimodally at the hypothalamus and at the pituitary gland, the sequelae in vivo being either stimulation or inhibition of gonadotropin secretion depending on a host of preconditions. Pituitary cells in culture were studied to characterize the acute action of progesterone on LH secretion. Preliminary studies established that anterior pituitary cells from adult female rats cultured for three days in 10% charcoal treated fetal bovine serum (c/t FBS) resulted in LH secretory responses to GnRH pulses which were half that for cells cultured in untreated FBS or c/t FBS + 0.2 nM 17 beta-estradiol (E2). Under standardized culture conditions (c/t FBS + E2), GnRH self-potentiation was evident. With this system, 90 min exposure to 200 nM progesterone resulted in a 3-fold augmentation of GnRH-stimulated LH secretion without affecting baseline LH. This action was manifested by 45 but not 15 min of progesterone exposure and was inhibited by simultaneous addition of cycloheximide. The augmentation of agonist-stimulated LH release could be elicited up to 4-5 h after progesterone addition. The estimated half-maximal effect was 10(-9) M, and this concentration of progesterone required E2-pretreatment of the cultured cells. In summary, addition of progesterone to cultured anterior pituitary cells pretreated with E2 leads to a concentration-, time-, and protein synthesis-dependent augmentation of pulsatile GnRH-stimulated LH secretion within 45 min of progesterone exposure. This rapid and unambiguous progesterone action in pituitary cells could function in vivo to define the final magnitude of the preovulatory LH surge. PMID- 2197083 TI - The Endocrine Society 1990 annual awards. PMID- 2197082 TI - Vascular endothelial growth factor is expressed in rat corpus luteum. AB - In the course of the development of the ovarian follicle and differentiation of granulosa cells into corpus luteum (CL), extensive changes in the microvasculature of these structures take place. This suggests the local release of angiogenic factors. In the present work we examined whether a newly described secreted vascular endothelial growth factor (VEGF) is expressed in normal rat ovary by in situ hybridization. Our results demonstrate the expression of VEGF in the CL but not in mural granulosa cells, suggesting a temporal relation between VEGF expression and growth of capillary vessels. The hybridization pattern in the CL was consistent with localization of VEGF message to luteal cells. Expression of VEGF was detected also in cumulus oophorus cells. These findings suggest that VEGF is involved in the process of CL angiogenesis. PMID- 2197084 TI - Transgenic Chinese hamster V79 cell lines which exhibit variable levels of gpt mutagenesis. AB - The Escherichia coli gpt gene coding for xanthine-guanine phosphoribosyl transferase has been stably transfected into HPRT- Chinese hamster V79 cells. Several gpt- cell lines have been established, which retain the sequence(s) even after long-term culture without selection for gpt. Each cell line exhibits a characteristic spontaneous mutation frequency (10(-5) to 10(-2)) in 6-thioguanine (6TG) selection. While spontaneous mutagenesis to gpt- occurs rather frequently for most cell lines, it cannot be correlated with either the number of plasmid integration sites or deletion of the plasmid sequence(s). One transgenic cell line (g12), which continuously maintains a low spontaneous mutation frequency (approximately 3 x 10(-5)), was used in comparative mutagenesis studies with wild type V79 cells (gpt vs. hprt). Alkylating agents such as N-methyl-N'-nitro-N nitrosoguanidine (MNNG) and beta-propiolactone (BPL) are shown to be equally toxic and mutagenic in both g12 and V79 cells. UV and X-rays are also equally toxic to both cell lines. The gpt locus of the g12 transfectants, however, is two to three times more sensitive to UV and 2.5-4.5 times more sensitive to X-ray mutagenesis than the endogenous hprt of wild-type V79 cells. The data presented here suggests that g12 cells may be useful to study mammalian mutagenesis by agents which yield limited response at the hprt locus. Future studies with these transgenic cells and other transgenic lines are planned to compare the mutability and repair of the same gene (gpt) at different integration sites in mammalian cells. PMID- 2197085 TI - The SIMULTEST approach for testing mutagens in the Salmonella microtitre fluctuation assay. AB - The concept of combining several histidine-dependent Salmonella strains in a single test, the SIMULTEST, has been applied to the microtitre fluctuation test. The activity of five mutagens was determined in strains TA97, TA98, TA100, and TA102 individually as well as in a SIMULTEST mixture. All five compounds were mutagenic in the SIMULTEST, demonstrating the utility of this time and labour saving approach of combining strains for testing with this method. The microtitre fluctuation SIMULTEST results were quantitatively comparable to those of the SIMULTEST Salmonella/microsome plate test. The microtitre fluctuation test compared with the plate incorporation assay generally showed more favourable "sensitivity" and "quantity" indices in that four of the five chemicals tested in the fluctuation test were mutagenic at lower doses than in the plate test. PMID- 2197086 TI - Genotoxic activity of benomyl in different test systems. AB - Benomyl (methyl-1-[butylcarbamoyl]-2-benzimidazole carbamate), a benzimidazole derivative fungicide, was tested in the Ames test for point mutations; in human lymphocyte cultures for cell division disturbances, chromosomal aberrations, and SCE; in rat bone marrow cells in vivo for micronuclei; and in rats in vivo for dominant lethals. Benomyl was negative in the Ames test. In human lymphocytes, benomyl at concentrations of 0.5, 1.0, and 2.0 micrograms/ml decreased the number of cells undergoing third division whereas at the concentrations of 0.25 to 4.0 micrograms/ml it strongly increased the number of aneuploid cells. Benomyl was also shown to induce sister chromatid exchanges and micronuclei but not chromosome aberrations. Benomyl decreased the number of female rats with implants but did not cause any dominant lethals. PMID- 2197087 TI - Study of mutational specificity in the lacl gene of Escherichia coli as a window on the mechanisms of mutation. AB - Whereas in the past we had to be content with mutation induction and survival curves, the recently developed technologies permitting the rapid cloning and sequencing of mutant alleles have provided a new window through which to examine the nature of mutation. These technologies make it possible to determine the precise nature of the mutational alteration as well as the local DNA context. This information has contributed significantly to our knowledge of the mutational process including the identification of likely pre-mutagenic lesions and the influence of DNA sequence and structure of the distribution of damage and its subsequent repair. This article discusses these issues as they relate to mutagenesis by alkylating agents. PMID- 2197088 TI - Insulin-like growth factors I and II. PMID- 2197089 TI - Characterization of the human cyclophilin gene and of related processed pseudogenes. AB - The human cyclophilin gene was isolated from a genomic library derived from leucocyte DNA and sequenced. The gene contains five exons and four introns. The amino acid sequence deduced from the exons matches perfectly the one previously determined from the T-cell cyclophilin cDNA. A TATA box is visible in the promoter region and putative Sp1 binding sites are also found there as well as in the first intron. Six members of the middle repetitive Alu gene family are present in one or other orientation in the non-coding regions of the cyclophilin gene. Hybridisation of genomic DNA to probes derived from the promoter region or the first intron indicates that the cyclophilin gene is present as a single copy in the human haploid genome. Seven other cyclophilin-related DNA clones isolated from the same library were also characterized. They show a high degree of similarity to the cyclophilin cDNA and are colinear to it. However, multiple genetic lesions, often including deletion and/or insertion events which modify the reading frame, are found in these clones which are therefore likely to represent processed pseudogenes. PMID- 2197090 TI - Regulation of glucokinase by a fructose-1-phosphate-sensitive protein in pancreatic islets. AB - In the post-microsomal supernatant of pancreatic islets, prepared from fasted or fed rats, D-fructose 1-phosphate increased the activity of glucokinase by 20-30% as measured in the presence of D-glucose 6-phosphate and D-fructose 6-phosphate. Such an activation was less marked than that found in liver extracts. The islet cytosol was also found to inhibit purified liver glucokinase, and this effect was antagonized by D-fructose 1-phosphate. In the presence of hexose 6-phosphates, partially purified islet glucokinase was inhibited by the hepatic glucokinase regulatory protein in a D-fructose-1-phosphate-sensitive manner. In intact islets, D-glyceraldehyde stimulated the generation of 14C-labelled D-fructose 1 phosphate from D-[U-14C]glucose and increased the production of 3H2O from D-[5 3H]glucose. These findings suggest that the activity of glucokinase in islet cells may be regulated by a protein mediating the antagonistic effects of D fructose 6-phosphate and D-fructose 1-phosphate in a manner qualitatively similar to that operating in hepatocytes, but with lower efficiency. PMID- 2197091 TI - Randomised double-blind study of norfloxacin and cefadroxil in the treatment of acute pyelonephritis. AB - In a coordinated, double-blind multi-centre trial, adults with symptoms of acute pyelonephritis were randomly assigned to receive a two-week course of oral treatment with either 400 mg norfloxacin twice daily or 1 g cefadroxil twice daily. Of 197 patients enrolled in the study, 140 could be evaluated for drug efficacy and 193 for drug safety. Norfloxacin gave a significantly higher bacteriological cure rate than cefadroxil, both at 3 to 10 days (98% versus 65%; p less than 0.0001; 95% confidence interval (CI) for difference in proportions 21 46%) and up to eight weeks (87% versus 48%; p less than 0.0001; 95% CI 25-54%) after cessation of treatment. The differences between the two regimens were most pronounced in men and in patients with complicating factors such as diabetes mellitus and urinary tract abnormalities. The clinical response during treatment did not differ between the two groups, but symptomatic recurrences at follow-up were more common in the cefadroxil group (28% versus 3%; p less than 0.0001; 95% CI 14-36%). Adverse events were more often reported by patients receiving cefadroxil (39% versus 22%; p = 0.011; 95% CI 4-30%) and consisted mainly of gastrointestinal disturbances and vulvo-vaginitis. In terms of bacteriological and clinical efficacy and safety, a two-week course of norfloxacin was superior to a two-week course of cefadroxil for oral treatment of community-acquired acute pyelonephritis. PMID- 2197092 TI - Isolation of fluoroquinolone-resistant Escherichia coli and Klebsiella pneumoniae from an infected Hickman catheter. AB - Escherichia coli and Klebsiella pneumoniae resistant to fluoroquinolones were isolated from an infected Hickman catheter in a 43-year-old diabetic patient who had previously been treated with a 24-day course of ciprofloxacin (200 mg/12 h i.v.). MICs and MBCs of nalidixic acid, norfloxacin, ciprofloxacin, ofloxacin, pefloxacin and fleroxacin were determined for the strains using the methodology recommended by the NCCLS. Both strains were resistant to all the quinolones tested. Since long-term treatment with quinolones might favour the emergence of quinolone resistance or colonization with quinolone-resistant organisms, it is important to monitor for the development of bacterial resistance during therapy with the new fluoroquinolones. PMID- 2197093 TI - Prevalence of antibodies to Chlamydia pneumoniae in a pediatric hospital population in Belgium. AB - To evaluate the prevalence of antibodies to Chlamydia pneumoniae in a pediatric hospital population, 207 patients admitted to the pediatric unit of the hospital during the period January to April 1989 were screened. A microimmunofluorescence test was used to measure both Chlamydia pneumoniae specific total antibody and IgM antibody. Fifty-eight (28%) patients were found to have antibodies to Chlamydia pneumoniae. Only one serum contained specific IgM. Analysis of the age specific prevalence of antibody showed a sudden rise in the 10 to 12 year old age group. Cross-reaction in the test with the other Chlamydia species is discussed. It is concluded that the incidence of primary Chlamydia pneumoniae infection during the study period was low, but that the infection occurs in Belgium with about the same prevalence as in other countries. PMID- 2197094 TI - A rapid test for detection of respiratory syncytial virus in nasopharyngeal secretion. AB - A new rapid membrane enzyme immunoassay (MEIA; Directigen RSV) for detection of respiratory syncytial virus (RSV) was evaluated using samples of nasopharyngeal secretion from infants and children with acute respiratory disease. The MEIA was compared with an immunofluorescent antibody (IF) technique using a sensitive biotin-avidin (BA) EIA as reference. Of 242 samples tested, 108 were positive by the MEIA and 123 by the BA-EIA. Of 144 samples which were also tested by the IF technique, 57 were positive by the BA-EIA and 43 by the IF technique. These results give a sensitivity of 86% and 72% for the MEIA and IF technique respectively. Of 57 samples found to be positive by the BA-EIA, 41 were positive by the IF technique, but 48 were positive by the MEIA. The MEIA is thus more sensitive than the IF technique but less sensitive than the BA-EIA in detecting RSV in nasopharyngeal secretions. PMID- 2197095 TI - Heart valve replacement with the Bjork-Shiley and St Jude Medical prostheses: a randomized comparison in 178 patients. AB - In 178 patients, a randomized prospective comparison between the 60 degrees spherical disc Bjork-Shiley (BS) and the St Jude Medical (SJM) heart valve prostheses was performed. Four-week perioperative mortality was zero in the BS (n = 84) and 4.3% in the SJM group (n = 94). During a mean (+/- SD) follow-up of 52 +/- 20 months or 778 patient-years, late cardiac mortality per year was 2.4% in the BS and 2.2% in the SJM group. The yearly thromboembolic rates were 1.4% in the BS and 2.0% in the SJM group. There was no mechanical valve failure or haemolytic anaemia. Paravalvular leaks and major bleeding complications occurred at low rates in both groups (1.1% and 2.2% per year in BS; 0.7% and 1.7% per year in SJM). Functional results were similarly good with 96% of patients with BS valves and 95% of patients with SJM prostheses being in NYHA classes I and II, respectively. We conclude that heart valve replacement with mechanical prostheses can be performed with equally good results using either the Bjork-Shiley spherical disc valve or the St Jude Medical bileaflet prosthesis. PMID- 2197096 TI - Edward Jenner (1749-1823). PMID- 2197097 TI - The interpretation of oesophageal pH monitoring data. AB - Continuous monitoring of oesophageal pH is regarded as the gold standard for all reflux investigations. However, since gastro-oesophageal reflux is considered a normal phenomenon which occurs to a certain extent in each individual, the distinction between "normal" and "abnormal" is not always obvious and is not possible to achieve with a single test. Moreover, data depend on technical hardware such as recording devices and electrodes together with such patient characteristics as age, position, activity, and medication. Although much literature on pH monitoring has appeared recently, many investigations have failed to take into account the basic principles that are of major importance for any biomedical test such as reproducibility, sample reliability, and indications. There is a need to standardize the technique in order to compare studies performed in different centres, provided the technique is reproducible. PMID- 2197098 TI - Effects of single doses of quinapril and atenolol on autonomic nervous function and exercise capacity in healthy volunteers. AB - The effects of single oral doses of the angiotensin converting enzyme (ACE) inhibitor quinapril (CI-906) 40 mg and the cardioselective beta-adrenoceptor blocker atenolol 100 mg on sympathetic and parasympathetic function and on exercise capacity have been studied in 8 healthy young men. The trial followed a double-blind, placebo controlled, randomized cross-over design, with at least one week between treatments. Blood pressure (BP) and heart rate (HR) at rest were slightly reduced by atenolol but were not affected by quinapril. Atenolol impaired the sympathetically mediated increases in HR and BP caused by standing, immersion of the hand into melting ice, the Valsalva manoeuvre and isometric forearm exercise. Quinapril did not influence those responses nor the vagally mediated bradycardia of the diving reflex. Atenolol, however, augmented the vagal bradycardia, presumably by sympathetic inhibition. In a dynamic bicycle ergometer test with a stepwise increasing work load, exercise performance was decreased by atenolol but not by quinapril. Inhibition of the renin-angiotensin system by quinapril was shown by a marked decrease in serum ACE activity and a several-fold increase in plasma renin activity (PRA). Atenolol produced a moderate reduction in PRA. Before or during exercise, plasma noradrenaline and adrenaline were not influenced by either drug. The results indicate that, unlike the atenolol-induced beta-adrenoceptor blockade, ACE inhibition by a single dose of quinapril had no clear effect on autonomic nervous function or exercise capacity. PMID- 2197100 TI - Alpha-1 proteinase inhibitor levels in keratoconus. AB - The levels of alpha 1-proteinase inhibitor (alpha 1-antitrypsin) in keratoconus, normal human, and other diseased corneas were examined. Using an immunoperoxidase technique, the presence of this inhibitor was demonstrated in the epithelium, stroma and endothelium of all corneal sections. Compared with normal human controls, the staining intensity in the epithelium and stromal lamellae of keratoconus corneas was markedly reduced. Such a reduction was not seen in either scarred or other diseased corneas. Extracts of keratoconus and normal human corneas were subsequently analyzed for alpha 1-proteinase inhibitor by a dot blot assay using a monoclonal antibody against the inhibitor and a 125I-labelled secondary antibody. In agreement with the immunohistochemical findings, the alpha 1-proteinase inhibitor level found in the epithelium of keratoconus corneas was approximately one-fourth of that found in normal human controls. In addition, the stromal extracts of keratoconus corneas contained about one-sixth the inhibitor level of that in normal human extracts. These results lend further support to the hypothesis that degradation processes may be aberrant in keratoconus. PMID- 2197099 TI - Metamizole: reassessment of its therapeutic role. AB - The use of metamizole is controversial, as reflected in the very different national regulations affecting it. The striking disparities between policies for metamizole made us try to determine if there were reasons to ban, limit or liberalize its utilization. After reviewing the literature, it was concluded that metamizole should not be withdrawn from the countries where its use is still relatively free. However, metamizole causes life-threatening adverse events that are usually unpredictable and can only be prevented by better prescribing habits, so it is suggested that its use as a first-line agent should be restricted to the treatment of the pain of acute colic and circumstances in which parenteral administration of a non-narcotic agent is mandatory. Studies are needed to determine the role of second-line oral analgesics in terms of their overall toxicity and efficacy. In the meantime it is proposed that oral metamizole should be used only when other analgesics (e.g. paracetamol) have failed. PMID- 2197101 TI - The origin of the intrinsic glycoproteins of the rabbit vitreous body: an immunohistochemical and autoradiographic study. AB - A cartilage matrix glycoprotein (CMGP), previously identified in human and bovine vitreous, now has been found in the vitreous body of rabbits aged 1-22 months by immunohistochemical techniques. Epithelial cells of the inner layer of the ciliary epithelium contain material that has immunologic cross-reactivity with a specific antibody to CMGP. These cells also secrete glycoproteins, as determined by autoradiography after intravitreal injection of [3H]fucose. Approximately 14 bands, representing intrinsic glycoproteins containing fucose residues, can be identified in fluorograms of SDS-polyacrylamide gels of vitreous bodies from 6- and 22-month-old rabbits. Fluorograms of gels of samples of vitreous and ciliary bodies from several time points after intravitreal injection of [3H]fucose reveal at least seven comigrating protein bands and also demonstrate turnover of the labeled ciliary body glycoproteins. These results suggest that the inner layer of the ciliary epithelium is the source of the glycoproteins of the vitreous body and that these glycoproteins undergo turnover, probably throughout the entire life of the animals. PMID- 2197102 TI - Jin H. Kinoshita International Symposium. 7 - 10 September, 1989. Proceedings. PMID- 2197103 TI - Intermediary metabolism of the lens: a historical perspective 1928-1989. PMID- 2197104 TI - Sorbitol pathway--reminiscences. PMID- 2197105 TI - Animal models for the study of maturity-onset and hereditary cataract. AB - The increasing use of animal models in the study of cataract has been one of the most important trends in lens research over the last two decades. The number of animal models available for both hereditary congenital cataracts and for maturity onset cataracts has grown substantially during this time. Analysis of some of these systems by biochemical and molecular biology techniques has resulted in significant and often surprising insights into the basic biology of the lens, as well as the process of cataractogenesis. The following is a brief overview of those animal models for which biochemical studies have been reported. PMID- 2197106 TI - Late onset hereditary cataract of the emory mouse. A model for human senile cataract. AB - The late onset cataract of the Emory mouse has appealed to many investigators as a useful animal model for human senile cataract. It has been the subject of about 15 publications, beginning in 1982. These have explored many features, including histology, chromatography and isoelectric focusing of the crystallins, enzyme profiles, amino acid and ion transport, membrane studies including changes in MP24 and MP26, analysis for a number of biochemical constituents, and its use as an assay system for testing the effect of anticataractogenic drugs and dietary restriction. These investigations have not uncovered a single metabolic lesion marked enough to be considered an important cause of this cataract. There is some evidence that the effect of oxidation may be a major factor; likewise there is evidence for faulty protein synthesis. In many cases, the changes in cataractogenesis appear to be accelerated aging changes. For this reason, any study of this cataract must employ age-matched controls of the cataract-resistant strain. A recent discovery is the finding that many earlier studies used a mixture of both early and late-onset forms, accounting for the wide variability in analytical results. The two substrains may have somewhat different applications in cataract research. Thus, the availability of these two substrains should extend the usefulness of this animal model. PMID- 2197107 TI - Hereditary cataract of the Nakano mouse. AB - The Nakano mouse is a hereditary cataract model whose most characteristic change is a deficiency in lens Na+,K(+)-ATPase. Consequently, there is a change in lenticular sodium and potassium ion levels just before cataract formation. The amounts of calcium ion also change suddenly in the lens, with accumulated levels higher than any other type of cataract. Other biochemical changes coincide with the development of lens opacity, including decreases in the levels of reduced glutathione, ATP, biosynthetic activity of proteoglycans in epithelial cells, and the permeability of gap junction channels in fiber cells. The decrease in the activity of Na+,K(+)-ATPase results in changes in a number of key metabolic parameters, resulting in the eventual opacification of the Nakano mouse lens at approximately 30 days of age. PMID- 2197108 TI - Role of site-specific, metal-catalyzed oxidation in lens aging and cataract: a hypothesis. AB - The evidence reviewed here supports the hypothesis that metal catalyzed oxidation reactions occur in the lens and may make a significant contribution to the changes seen in the lens with age and in cataract formation. The major support for this hypothesis is as follows. (1) All of the components of the non-enzymic metal catalyzed oxidation systems are present in the lens normally. Ascorbate, glutathione and oxygen are present in much lower concentrations. Although, even at low concentrations, the reactions could occur over many years with significant consequences. Components of some of the enzymic systems are also present, although primarily in the epithelial layer and outer cortical region. Copper and iron levels may be increased in some cataracts. (2) Protein carbonyl derivatives are increased in both aging and cataractous lenses. Amino acid-derived protein carbonyl derivatives have only been demonstrated in oxidative reactions derived from oxygen radical generation, particularly those catalyzed by metal-catalyzed oxidation systems. (3) Treatment of isolated bovine crystallins with metal catalyzed oxidation systems generates modifications similar to those found in vivo. The proposed mechanism of site-specific metal catalyzed oxidation appears to be a feasible mechanism of oxidation in the lens, and verification of the mechanism requires further study. Although the focus of this manuscript has been on the oxidative modification induced in proteins,m oxidative damage to DNA or membrane resulting from similar mechanisms may also play an important role in alteration of lens function during aging and cataractogenesis. PMID- 2197109 TI - Some aspects of Dr Kinoshita's contributions to lens protein chemistry. AB - A review of some of Dr Kinoshita's contributions to our understanding of lens protein and glutathione biochemistry is presented. Particular emphasis is placed on Dr Kinoshita's work involved with the relationship of carbohydrate metabolism and the maintenance of reduced glutathione, the question of the biological function of glutathione in the lens, the effect of oxidative stress provided by diamide and azoester on glutathione, membrane pump function and protein and also ascorbate and H2O2 effects on Na+, K(+)-ATPase. The importance of oxidative stress was recognized early by Dr Kinoshita and he has continued to make significant contributions in this area as illustrated by his work with Dr Zigler on posterior subcapsular cataracts and with Drs Garland and Zigler on mixed function oxidation. It is concluded that Dr Kinoshita's overall contributions in the areas mentioned above have been broad and of considerable importance. PMID- 2197110 TI - Molecular biology: recent studies on enzyme/crystallins and alpha-crystallin gene expression. AB - Jin H. Kinoshita has had a major role in fostering investigations on the molecular biology of the eye during his tenure as Scientific Director of the National Eye Institute (N.E.I.). His appreciation and support of molecular biology have been the basis for many advances in this area in the N.E.I. and have led to a fertile breeding ground for molecular studies on the normal and diseased eye. Our recent studies have shown that the taxon-specific crystallins have been recruited from numerous metabolic enzymes; they are expressed in the lens as abundant structural proteins and in other tissues as enzymes, a situation we call gene sharing. Although not taxon-specific, alpha B-crystallin, structurally related to the small heat-shock proteins, is expressed in diverse tissues; by contrast, alpha A-crystallin appears to be lens-specific. Recombinant DNA studies indicate that the two alpha-crystallin genes use different promoter sequences and trans factors for their expression. Thus, the ubiquitous alpha-crystallin genes may provide some insight into the mechanisms used to recruit metabolic enzymes as taxon-specific lens crystallins. PMID- 2197111 TI - S-antigen: from gene to autoimmune uveitis. AB - Retinal S-antigen (S-Ag) is capable of inducing experimental autoimmune uveitis (EAU) in laboratory animals. EAU may serve as an animal model for studying human uveitis. As a first step we have determined the nucleotide sequence of an S-Ag gene and its cDNAs. The amino acid sequences were deduced from the cDNAs of various animals and human. Four uveitopathogenic sites in bovine S-Ag were characterized. One of the sites (peptide M) has sequence homology with non-self proteins from baker's yeast, potato, E. coli, hepatitis B virus, moloney murine leukemia virus, Moloney murine sarcoma virus, AKR murine leukemia virus and baboon endogenous virus. Mononuclear cells from animals immunized with peptide M showed significant proliferation when incubated with synthetic peptides corresponding to the amino acid sequences of the above-mentioned foreign proteins. In addition, all the peptides induced EAU in Lewis rats with a dose of 10-2000 micrograms. Moreover, native histone H3 from baker's yeast histone H3 induced EAU in Lewis rats. Thus, we found several examples of antigenic mimicry between self and non-self proteins. These findings establish a base to study further the mechanism of autoimmune inflammation. PMID- 2197112 TI - Glutathione and its function in the lens--an overview. AB - This paper presents an overview of the current state of our knowledge concerning the metabolism and function of glutathione (GSH) in the lens, with particular reference to the contributions of Dr Jin H. Kinoshita to this field. Glutathione in the lens is synthesized from its constituent amino acids and degraded by mechanisms involving transpeptidation and hydrolysis. The turnover of GSH in the lens is due to its catabolism rather than transport of GSSG as is the case in red blood cells and some other tissues. Three aspects of the functional role of GSH in cataract formation are considered. First, GSH may be important in maintaining protein thiols in the reduced state, thus preventing the formation of high molecular weight protein aggregates which are the basis for light scattering and lens opacification. A second function may be to protect membrane -SH groups that are important in cation transport and permeability. A third functional role is to detoxify hydrogen peroxide and other organoperoxides. The glutathione redox cycle is intimately involved in the detoxification of H2O2 which is normally present in the aqueous humor. PMID- 2197113 TI - Plasmodium falciparum: analysis of chromosomes separated by contour-clamped homogenous electric fields. AB - We have established improved conditions for separating the chromosomes of Plasmodium falciparum by pulsed field gradient gel electrophoresis (PFG) using a contour-clamped homogenous electric field (CHEF) apparatus. Thirteen clearly separable chromosomal bands were reproducibly isolated from the strain FCR3 and their sizes have been determined. Evidence that indicates one band may contain two chromosomes is presented. The relationship between the PFG separable DNA and the number of unique chromosomes in P. falciparum is considered. We have established a relationship between the maximum resolvable sizes of the chromosomes and the pulse times. The chromosomal location of twenty-seven P. falciparum DNA probes is also reported. PMID- 2197114 TI - Biosynthesis of the 25-kDa protein in the macrogametes/zygotes of Plasmodium falciparum. AB - Synthesis of the 25-kDa protein in the early midgut stages of Plasmodium falciparum was studied, using metabolic inhibitors (colchicine and actinomycin D) and pulse-labeling experiments. Experiments with colchicine showed that, immediately after induction of macrogametogenesis, 25-kDa protein synthesis occurs in both fertilized and nonfertilized macrogametes. The amount of 25-kDa protein synthesized increased slowly during time. Experiments with actinomycin D revealed that the slow increase of synthesis may be dependent on de novo messenger RNA synthesis. PMID- 2197115 TI - The acid-active hemolysin of Trypanosoma cruzi. PMID- 2197116 TI - Immunocytochemical demonstration of contractile cells in the human ovarian follicle. AB - Actin- and myosin-like immunoreactivity is found in cells located in the theca externa of the follicle wall of the human ovary, and corresponding to previously observed myoid cells. The immunocytochemical observation provides direct structural evidence that non-vascular contractile cells are also present in the follicle wall in humans. As expected, perifollicular blood vessels showed a positive immunoreaction for actin and myosin in their smooth muscle walls. PMID- 2197118 TI - Historic review of the management of tooth hypersensitivity. AB - For well over a century, there has been cognizance that sensitivity is a serious problem, that it arises when the dentin and cementum are exposed, that fluid movement within the dentinal tubules acts as a provocative stimulus, that tubules can be sealed off (apparently in most instances) without damage to the tooth or the dental pulp, and that the problem can also be at least partially resolved by suppressing nerve firing within the pulp. Most of the therapies proposed to date for treatment rely on one of two major suppressive mechanisms, that is, sealing off the dentinal tubules or dampening neural impulses, even though at the time of their development and use they have been mostly empiric in nature. At present, there appear to be a number of effective therapies, although admittedly none meet all of the hypothetic requirements proposed by Grossman over 50 years ago. Included among the agents with reasonable documentation of effectiveness and little in the way of negatives are fluorides, strontium chloride, potassium nitrate, potassium oxalate, sodium citrate, surface sealing agents (varnishes, resins, cyanoacrylate), calcium hydroxide, and others. There are many dedicated workers who are still concerned with achieving better insight into the problem and methods to resolve it. PMID- 2197117 TI - Prothoracic gland synthesis of 3-dehydroecdysone and its hemolymph 3 beta reductase mediated conversion to ecdysone in representative insects. AB - The prothoracic glands of a variety of insects were tested for their ability to synthesize ecdysteroids in vitro. More specifically, they were evaluated for their ability to produce 3-dehydroecdysone and ecdysone using both radioimmunoassay and reverse phase high performance liquid chromatography. Three categories of insect prothoracic glands were noted: a) those producing much more 3-dehydroecdysone than ecdysone; b) glands synthesizing almost equivalent amounts of each of these two ecdysteroids; c) prothoracic glands that yielded more ecdysone than 3-dehydroecdysone. In addition, the 3-oxoecdysteroid 3 beta reductase activity of the hemolymph of these insects was evaluated for its ability to convert 3-dehydroecdysone to ecdysone. The lepidopteran species tested yielded the most potent enzyme activity, although activity was demonstrated in members of other orders. These data indicate that the dehydroecdysone-ecdysone axis is not restricted to moths and butterflies. PMID- 2197119 TI - Tooth hypersensitivity in the spectrum of pain. AB - Dentinal hypersensitivity satisfies all the criteria to be classified as a true pain syndrome that can be acute, but for our purposes is a chronic condition with acute episodes without the disabling characteristics and severe dysfunction of a chronic pain syndrome. It is estimated that the frequency of dentinal hypersensitivity affects one of six people, and one or more teeth can be affected. The incidence of dentinal hypersensitivity appears to peak around the third decade of life and may appear as root sensitivity in the fifth decade of life as root sensitivity particularly in patients undergoing periodontal surgery. The relationship of dentinal hypersensitivity to acute and chronic pain is shown in Table 1. Dentists' ability to soothe or stop pain has always been their greatest asset in establishing patient rapport. The experience of pain is so subjective that none of us can ever be sure another person is having it. Physicians, dentists, and especially those affiliated with pain centers and clinics have resolved this dilemma in a commonsensical way. They simply treat the pain as if it were real, and their track record in confronting this inscrutable condition has contributed to their high regard as professionals. PMID- 2197120 TI - The neurophysiology of the teeth. AB - Irritation of human teeth can evoke pain sensations of varying qualities depending on the type and intensity of the stimuli used. For example, drilling or air drying of dentin typically induces sharp, piercing pain, while intense heating of the tooth can cause dull, aching pain sensation. The dental pulp is richly innervated by both myelinated (A-fibers, mostly A delta-type) and unmyelinated (C-fibers) axons. A-fibers seem to be responsible for the sensitivity of dentin. They respond to stimuli that induce sharp pain in human teeth, for example, drilling of dentin and drying of dentin with air blasts. C fibers are activated only when the stimuli used reach the pulp proper. They respond to intense heating. In human teeth, dull pain is induced at a temperature level corresponding to the heat thresholds of intradental C-fibers. The other functional characteristics of C-fibers indicate that they may play a role in the mediation of the dull pain connected with pulpal inflammation. Accordingly, activation of intradental nerve fibers of A- and C-type may contribute to the varying qualities of pain sensations induced by stimulation of human teeth. PMID- 2197121 TI - Mechanisms of dentin sensitivity. AB - This article reviews dentin sensitivity from a mechanistic perspective beginning with short treatments of pulpal innervation, the hydrodynamic considerations of dentin, and how various stimuli may cause pain. Speculation is raised about the contribution of bacteria and their products on dentin sensitivity and how dentin might become truly hypersensitive, especially following periodontal therapy. Wherever possible, the clinical considerations of basic research is stressed. PMID- 2197122 TI - Dentinal permeability in assessing therapeutic agents. AB - The measurement of dentinal permeability has been useful in confirming the mechanism of the hydrodynamic hypothesis for pain transmission in hypersensitive patients, has advanced our understanding of how neural agents can reach the pulpal nerves, and has provided useful data to compare and evaluate therapeutic agents. Methods to assess permeability have varied from direct dye penetration techniques to measurement of fluid flow through dentin sections to SEM photography of impression replicas in vivo. A number of clinical therapeutic strategies have emerged from this work as well as ways to mitigate the progressive nature of the condition. PMID- 2197123 TI - Hypersensitive teeth. Experimental studies of dentinal desensitizing agents. AB - The effect of dentinal desensitizing agents on nerve activity was tested. Effective agents such as KNO3 reduce dentinal sensory nerve activity. This effect is due to the depolarizing action of the K+ ion. PMID- 2197124 TI - Etiology and clinical implications of dentine hypersensitivity. AB - In conclusion, if dentine hypersensitivity is to be prevented or more effectively managed, greater consideration must be given to the etiology of the condition than has been the norm to date. In established cases of dentine hypersensitivity, exclusion of other possible causes of pain is essential by considering a differential diagnosis. Management requires the determination of etiologic factors and predisposing influences, and where possible, their control or modification. In particular, the presence of erosive elements should be identified and separated from abrasive influences such as toothbrushing. To ensure the successful management of the clinical implications of dentine hypersensitivity, a careful assessment of the etiologic factors must be considered in evaluating the dental patient presenting with these symptoms. PMID- 2197125 TI - Methods of measuring tooth hypersensitivity. AB - Thermal, tactile, osmotic, and electrical stimuli, as well as exposure to air, can each elicit a painful response in individuals with hypersensitive teeth, and thus provide the basis for the different methods used to measure dentinal hypersensitivity. Tactile methods range from simple use of a sharp dental explorer to devices that can quantify the probing or scratching pressure exerted generally along the cementoenamel junction. Thermal methods involve flow of air or metal probes applied in different ways. Electrical stimulus is more complex and generally consists of progressive elevation of the magnitude of the stimulus until a sense of prepain rather than pain is felt. More than one method is usually needed in order to assess dentinal hypersensitivity, which has been estimated to affect one in every seven patients that visit a dental office. PMID- 2197126 TI - Designing hypersensitivity clinical studies. AB - A dentinal hypersensitivity study is really a clinical pain study. The fundamental difficulties in reproducibly and reliably measuring pain impact heavily on the study. Other critical issues include investigator and subject selection, study design, randomization strategy, study duration, sample size, and statistical analysis. This article discusses principles involved in establishing the efficacy of a desensitizing agent. PMID- 2197127 TI - Over-the-counter dentifrices in the treatment of tooth hypersensitivity. Review of clinical studies. AB - Dentinal hypersensitivity is a common condition. Most cases, after professional diagnosis, can be treated simply and inexpensively by home use of a desensitizing dentifrice. Because the habit of toothbrushing with a dentifrice for cosmetic reasons is well established in the population, compliance with this regimen is not a problem. Dentifrices incorporating potassium nitrate, strontium chloride, and dibasic sodium citrate have all been clinically determined to be effective desensitizers, and several brands have been critically evaluated and accepted by the Council on Dental Therapeutics of the ADA. During the years, clinical methodology has evolved from monadically designed, subjective investigator reports to present-day, double-blind, placebo-controlled clinical trials employing stimuli that are quantifiable in physical units. Future development of more effective desensitizing dentifrices will depend on standardization in clinical design, especially regarding stimulus choice and mode of application. PMID- 2197128 TI - A review of current approaches to in-office management of tooth hypersensitivity. AB - In-office treatment of dentinal hypersensitivity should be capable of providing the patient with immediate and lasting relief of pain. Regardless of the type of treatment employed, 20 to 40 per cent of hypersensitive teeth usually improve over a period of 4 to 8 weeks. Partial obturation of open tubules is the most widely practiced treatment, with other forms of therapy being recommended as a backup for patients in whom this approach fails. Obturation can be achieved with topical application of agents that form insoluble precipitates within the orifices of the tubules. Burnishing the exposed root surface produces a smear layer, which in itself can significantly reduce dentin permeability. At times, the use of a restorative resin or dentin bonding agent can be successful in reducing sensitivity when other forms of therapy have failed. Proper patient management should stress dietary counseling when dietary acids are an important etiologic factor. The importance of proper tooth brushing and plaque control must be stressed. At the present time, the use of oxalates for the obturation of tubules shows promise as a future in-office clinical agent; however, further clinical studies are required to evaluate and compare their efficacy with other currently effective methods and agents. PMID- 2197129 TI - The Golgi apparatus: insights from lipid biochemistry. PMID- 2197130 TI - The relationship between cytoplasmic free Ca2+ and the release of glutamate from synaptosomes. PMID- 2197131 TI - Characterization of novel post-synaptic-density-enriched glycoproteins gp130 and gp117 with a monoclonal antibody. PMID- 2197133 TI - A novel approach to reduce background colour development by diaminobenzidine in peroxidase-based assays. PMID- 2197132 TI - Dystrophin and dystrophin-like proteins in muscle and brain of normal and mdx mice. PMID- 2197134 TI - Calmodulin involvement in Ca2(+)-induced insulin release from electropermeabilized islets of Langerhans. PMID- 2197135 TI - Effects of capsaicin on glucose metabolism in isolated incubated skeletal muscle in vitro. PMID- 2197136 TI - A sequence-specific protease cleaves a maternal, cortical protein during early embryogenesis in Sciara coprophila (Diptera). AB - One of the first events of egg activation in Sciara coprophila (Diptera) is the disappearance of an abundant maternal 38-kDa protein (p38) and the simultaneous emergence of an abundant 35-kDa protein (p35). Western blotting experiments using monoclonal antibodies directed against p38 reveal that p38 and p35 are serologically related and indicate that maternal p38 is transformed into p35 during early development. This transition is possibly accompanied by a conformational change in the part of the protein that is common to both protein species. The processing of p38 to p35 can be mimicked by trypsin treatment in vitro, suggesting that a trypsin-like protease is responsible for this conversion in vivo. Immunostaining indicates that the p38 class of antigens is evenly distributed in the periplasm of early cleavage embryos. After the arrival of nuclei in the periplasm, the antigens become associated with the infolding cellular membranes. A similar membrane association of actin can be observed with anti-actin antibodies. Nevertheless, p38 and actin are clearly distinct from each other. We presume that p38 is a product of a maternal effect gene necessary for early dipteran development. PMID- 2197137 TI - Development of the hypothalamic luteinizing hormone-releasing hormone-containing neuron system in the rat: in vivo and in transplantation studies. AB - The development of the hypothalamic LHRH-containing neuron system was immunohistochemically investigated in vivo and in tissue transplantation using rat embryos aged from 12.5 to 17.5 days of gestation. The sera used were generated against rat gonadotropic hormone-releasing hormone-associated peptide (28-56) (rGAP) and LHRH. Immunoreaction for rGAP was first found in cells migrated from and in the vomeronasal organ on Days 13.5 and 14.5 of gestation. Immunoreactive cells seem to ascend along the terminal nerves, reaching the medial surface of the forebrain vesicles. Subsequently the cells occurred in the septum and further into their final position in the septopreoptic-diagonal band area on Days 16.5-17.5 of gestation; during this traverse the cells become secretory neurons after changes in morphology and in behavior. Intraventricular transplantation revealed that nasal epithelia of Day 12.5 embryos raised only a few cells immunoreactive both for LHRH and rGAP, but a great number of immunoreactive cells and fibers in the presence of the medial basal hypothalamus (MBH). The fibers formed a median eminence-like structure together with dense capillary plexus that had grown in the cografted MBH. The same phenomenon was apparently observed in the grafts obtained from older embryos of gestation, but not in the combined grafts of the anterior septum and the nasal epithelium or the MBH. We conclude that hypothalamic LHRH neurons originate from the nasal placode and acquire secretory behavior in the presence of the MBH. PMID- 2197138 TI - Transgenic mouse models of type I diabetes. AB - Transgenic mouse technology has gained recognition as an important tool for examining many fundamental biological questions in vivo. Recently, transgenic mouse techniques have been applied to the study of type I (insulin-dependent) diabetes. These studies have been particularly informative in elucidating 1) mechanisms whereby immune tolerance is maintained to antigens on rare specialized cells such as the pancreatic beta-cell, 2) disease susceptibility and resistance genes, and 3) potentially important immune effector mechanisms. In this article, we discuss these studies, their impact on understanding of the pathogenesis of type I diabetes, and the potential of the transgenic mouse approach for future research. PMID- 2197139 TI - Insulitis and diabetes in NOD mice reduced by prophylactic insulin therapy. AB - Intensive insulin therapy in patients with recently diagnosed insulin-dependent diabetes mellitus (IDDM) has been reported to result in a prolonged increase in endogenous insulin-secreting capacity. Because the clinical onset of IDDM occurs only after most insulin-secreting beta-cells have been destroyed, we tested whether prophylactic insulin therapy might prevent IDDM in nonobese diabetic (NOD) mice. One hundred fourteen NOD mice were randomized at weaning into a protamine zinc pork insulin-treated (I) group or a placebo-treated (P) group given insulin diluent. All insulin treatments were adjusted to the maximum tolerable dosages and continued until 180 days of age. The cumulative IDDM frequency within the female I group was significantly less (3 of 34, 8%) than in female P controls (17 of 26, 65%; P less than 0.0001). This beneficial effect was limited to females, however, because the frequency of IDDM in male I mice (3 of 32, 9%) was not significantly different from the frequency in male P controls (1 of 22, 5%; P less than 0.5). Pancreatic histological examinations of nondiabetic animals revealed that insulin treatment resulted in significant reductions in islet cell inflammation and damage and improvements in insulin content. In summary, NOD mice given insulin therapy from weaning until 180 days of age had significantly lower frequencies of diabetes and pancreatic insulitis than sex matched control littermates treated with insulin diluent. These results suggest that prophylactic insulin therapy to prevent IDDM in humans should be considered for clinical trials. PMID- 2197141 TI - Self-replication of enterochromaffin-like cells in the mouse stomach. AB - The renewal mechanisms for enterochromaffin-like (ECL) cells, the predominating endocrine cell population in the oxyntic mucosa of the stomach, were investigated in the mouse. The ECL cells were selectively demonstrated by immunostaining using histamine antibodies. Under basal conditions, when observed during the night, ECL cells in mitosis could be seen. This observation proved their ability to divide. Autoradiography after a single pulse and after multiple injections of 3H thymidine made it possible to study some of their cytokinetic characteristics. The observed replication rate of the labeled ECL cells suggested that self replication is the main mechanism by which the ECL cell population is renewed. The time interval between two successive divisions of labeled ECL cells was estimated to be around 60 days. Since ECL cells proliferate through mitosis, it may be expected that specific mitogenic stimuli might promote the induction of ECL cell hyperplasia and eventually ECL cell tumors (gastric carcinoids). PMID- 2197140 TI - Kinetics of in vivo muscle insulin-mediated glucose uptake in human obesity. AB - The kinetics of in vivo insulin-mediated glucose uptake in human obesity have not been previously studied. To examine this, we used the glucose-clamp technique to measure whole-body and leg muscle glucose uptake in seven lean and six obese men during hyperinsulinemia (approximately 2000 pM) at four glucose levels (approximately 4.5, approximately 8.3, approximately 13.5, and approximately 23.5 mM). To measure leg glucose uptake, the femoral artery and vein were catheterized, and blood flow was measured by thermodilution (leg glucose uptake = arteriovenous glucose difference x blood flow). With this approach, we found that rates of whole-body and leg glucose uptake were significantly lower in obese than in lean subjects at each glucose plateau. Leg blood flow rates increased from 4.3 +/- 0.4 to 6.5 +/- 0.8 dl/min over the range of glucose in lean subjects (P less than 0.05) but remained unchanged in obese subjects. The apparent maximal capacity (Vmax), based on whole-body and leg glucose uptake, was reduced in obese compared with lean subjects, but the apparent Km was similar in the lean and obese subjects (6-9 mM, NS). To assess the affinity of muscle for glucose extraction independent of changes in muscle plasma flow, we determined the mean half-maximal effective glucose concentration (EG50) and found it was similar in the lean and obese subjects (6.0 +/- 0.3 vs. 6.0 +/- 0.8 mM, NS). We conclude that 1) the kinetics of in vivo insulin-mediated glucose uptake in skeletal muscle in human obesity are characterized by reduced Vmax but normal Km; 2) the EG50 for insulin-mediated glucose extraction in skeletal muscle was 6 mM in both lean and obese subjects, consistent with a Km characteristic of the glucose transport system; 3) obese subjects were unable to generate increases in blood flow in response to hyperglycemia under hyperinsulinemic conditions, and this contributed significantly to lower rates of leg and whole-body glucose uptake. PMID- 2197142 TI - Smooth muscle actin expression during rat gut development and induction in fetal skin fibroblastic cells associated with intestinal embryonic epithelium. AB - Cytodifferentiation of smooth muscle cells has been analyzed immunocytochemically during rat intestinal development and in chimaeric intestines by using monoclonal antibodies reacting specifically with smooth muscle actin species (CGA7 [10] and anti-alpha SM-1 [40]). As development proceeds, the various intestinal muscle layers differentiate in the following order: (1) cells expressing smooth muscle actin appear within the mesenchyme of the 15-day fetal rat intestine, in the circular muscle-forming area, the differentiation of cells in the presumptive longitudinal muscle layer starting with a 48-h delay; (2) smooth muscle fibers appear within the connective tissue core of the villi shortly after birth, in parallel with a progressive formation of the muscularis mucosae, which becomes clear-cut only in the course of the 2nd week after birth; (3) a distinct cell layer in the innermost part of the circular muscle layer arises during the perinatal period. Thereafter, the fluorescence pattern remains unchanged until the adult stage. Chimaeric intestines were constructed by the association of 14 day fetal intestinal epithelium and cultured fetal rat or human skin fibroblasts. These fibroblastic cells did not express actin at the time at which they were associated. The immunocytochemical analysis of smooth muscle actin in the hybrid intestines, which had developed as intracoelomic grafts for 12 days, revealed that the skin fibroblastic cells had been induced by the intestinal epithelial cells to differentiate into smooth muscle cells. Such a result was also obtained with allantoic endoderm. It was not obvious in cocultures of intestinal epithelium with skin fibroblastic cells. However, when intestinal epithelial cells were cocultured with intestinal mesenchymal cells, actin expression was stimulated in the latter cell population. PMID- 2197143 TI - Contributions of the laboratory animal veterinarian to refining animal experiments in toxicology. AB - Although most people support the appropriate use of animals for research and safety testing, the public expects that animals will be treated in a humane manner. The advancement of science and the ethical considerations of animal use are not antithetical. Toxicologists should be cognizant that animal pain and distress may result from their studies and should recognize their duty in minimizing or preventing this potential outcome. While the ultimate responsibility for preventing animal pain and distress is with the individual toxicologist, the responsibility for the well-being of laboratory animals is shared with the Institutional Animal Care and Use Committee (IACUC) and the veterinary staff. The role of the veterinarian in working with toxicologists to refine animal studies is multifaceted and includes such activities as assisting in the planning stages of studies and in presubmission review of protocols, providing training in anticipation and recognition of pain and distress, providing information concerning pharmacologic and nonpharmacologic methods for alleviating or minimizing pain and distress, providing a high quality animal care and health program to support studies, and assisting toxicology staff in monitoring all phases of the study and in addressing problems in a timely manner. Veterinarians, toxicologists and IACUCs are faced with a significant, but not insurmountable, challenge in the prevention and alleviation of pain in research animals. We are beginning to categorize and agree upon subjective signs of pain and distress in various laboratory species. More research is required to develop more objective methods for recognizing pain and for providing better methods for prevention and alleviation. PMID- 2197144 TI - Refinement of animal research technique and validity of research data. AB - Refinement of research techniques using animals will lead to less animal distress and, at the same time, will usually lead to higher quality and more robust data. For example, acclimation of laboratory animals to handling and experimental procedures will produce not only an animal that is easier to handle but also one that reacts to the experimental stimulus rather than to the handler. Even when the animal is acclimated to handling, handling or anesthesia can cause marked changes to commonly measured biological parameters such as serum hormone and tissue metabolite levels. Standard animal housing systems are also stressful to the animals. One research report, for example, found that mice in conventional facilities had plasma corticosterone values of 150-500 ng/ml compared to values below 35 ng/ml from mice kept in special "low-stress" housing. However, assessment of stress in animal research is not easy and few technicians or research scientists are good judges of moderate stress. Investigators in the United Kingdom have recently published a report on a new technique that might allow more objective assessment of discomfort in laboratory rats and mice. The amount of exploratory behavior in treated and control animals can be used for developing a Disturbance Index (DI). The DI is a measure of the extent to which a procedure or treatment causes a departure from normal behavior. The initial data using the DI indicate that it could be a promising approach for assessing animal well-being (or the lack of it). PMID- 2197145 TI - Refinement of long-term toxicity and carcinogenesis studies. AB - The chance that alternatives will completely replace animals for toxicology research in the foreseeable future is nil. Continual refinement of animal toxicity and carcinogenesis studies, however, can be an effective means of reducing the numbers of animals used and conserving time and resources without compromising scientific quality. We must continue to strive to find species and strains that can metabolize chemicals similar to humans, are small enough to be housed in large numbers, and have low prevalence of spontaneous lesions with sufficient life span to express the toxic and carcinogenic potential of chemicals. Adequate care of animals with control of variables such as light, temperature, diet, bedding, diseases, and genetic characters of laboratory animals will decrease the variability. Humane considerations and euthanasia of animals with large masses and other conditions interfering with eating and drinking, major injuries and ulcers related to husbandry and treatment, and diseases indicating pain and suffering will help not only to alleviate further pain and distress but also to facilitate collection of tissues without secondary complications for detection of chemical treatment-related lesions. Limiting the duration of studies to decrease the variability due to age-associated changes will also refine long-term studies. Other considerations for refinement of carcinogenesis studies include selection of the most sensitive sex of one or more species for evaluation of selected chemicals in a class where toxic and carcinogenic potential of other representative chemicals are known. Genetically engineered animal models with known oncogenes may reduce the duration and increase the sensitivity of carcinogenesis studies with a reduction in the use of animals. PMID- 2197146 TI - Comparison of assays for gap junctional communication using human embryocarcinoma cells exposed to dieldrin. AB - Several assays were compared for their ability to detect inhibition of gap junctional communication in human embryocarcinoma cells exposed to the pesticide dieldrin. Included in this evaluation was a recently developed assay based on the transfer of the fluorescent dye derived metabolically from 5(and 6)-carboxy-2,7 dichlorofluorescein diacetate. This assay was compared to assays for fluorescence return after photobleaching (FRAP), transfer of Lucifer yellow after scrape loading, autoradiographic visualization of [3H]-uridine nucleotide transfer, and metabolic coupling of 6-thioguanine (6-TG) metabolites. The scrape-loading assay was the most sensitive assay, detecting inhibition of junctional communication at all concentrations tested. Additionally, the scrape-loading assay provided the clearest demonstration of concentration-dependent inhibition of junctional communication, although the [3H]uridine assay also showed significant concentration-related effects. The 5(and 6)-carboxy-2,7-dichlorofluorescein diacetate and 6-TG metabolic coupling assays detected significant inhibition at the two highest concentrations of dieldrin only. The FRAP assay also detected substantial inhibition at the two highest concentrations only. These results show that scrape-loading is the most sensitive assay of those compared in this study for the detection of inhibited junctional communication. Furthermore, compared to the other assays evaluated, the newly developed 5(and 6)-carboxy-2,7 dichlorofluorescein diacetate assay is at least as sensitive, yet less cumbersome, less expensive, and more rapid. Finally, the results show that each of these assays was easily applied to embryonic cells, suggesting that they may be useful for evaluating disruption of junctional communication in embryonic cell cultures. PMID- 2197147 TI - Recent developments in replacing, reducing, and refining animal use in toxicologic research and testing. AB - Significant progress has been made in replacing animals in toxicology/safety assessment with in vitro systems, in reducing the number of animals used, and in refining how they are used. Review of annual reports of the numbers of animals used in testing in the United States, the United Kingdom, and Japan shows a continuing reduction in the numbers for all species. Multiple in vitro systems have been developed for screening/testing for eye and skin irritation, skin sensitization, teratology, and other endpoints and a scientific consensus has been formed on requirements and process for validation. However, the use of these test systems in place of existing in vivo tests is minimal. At the same time, innovative designs have been developed (and are in wide use) for in vivo tests which reduce both the numbers and the pain and distress of animals used in testing. Progress and dialogue continue on modification of both U.S. and international requirements and guidelines for testing, and for defining an "approval" process for alternatives and innovations. PMID- 2197148 TI - [The characteristics of the processing of visual information in the right and left hemispheres of the human brain]. PMID- 2197149 TI - [The neurophysiological correlates of the system of supraspinal regulation of muscle tonus in parkinsonism]. PMID- 2197150 TI - [The interpretation of an expert classification of the human EEG in machine analysis terms]. PMID- 2197151 TI - Cystic fibrosis: a disease in electrolyte transport. AB - Cystic fibrosis (CF) is a fatal genetic disease caused by abnormalities in fluid and electrolyte transport in exocrine epithelia. Both absorptive and secretory processes are affected by an underlying membrane defect in Cl- permeability. However, the impact of the defect on transport function is tissue specific. Net electrolyte absorption is decreased in the sweat duct, increased in airway epithelia, and not affected in intestine. The defect is expressed in secretion as a consistent failure in most, if not all, exocrine tissues, to beta adrenergically stimulated and cAMP mediated secretory response. However, the secretory response to cholinergic and Ca2(+)-mediated stimulation is normal in the sweat gland, apparently normal in the airway, but absent in the intestine. The basic defect is not fatal in and of itself, and the imbalance between absorption and secretory functions may be of some selective advantage to heterozygotes in surviving complications of intestinal infections. The inherent defect in transport is probably the primary physiological cause of the ultimately fatal secondary infections in the lungs of CF homozygotes. PMID- 2197152 TI - Prospects for specific immunotherapy in myasthenia gravis. AB - Myasthenia gravis is an autoimmune disease resulting from a breakdown in T and B cell tolerance to acetylcholine receptor (AChR). Autoantibodies to AChR mediate the disease. Recent advances in experimental immunotherapy of autoimmune disease provide several possibilities for specific intervention in this well characterized condition. PMID- 2197153 TI - Asthma: a disorder of adrenergic receptors? AB - For the past 20 years, the hypothesis that bronchial asthma represents an imbalance between deficient activity of the beta-adrenergic receptor pathway and/or enhanced activity of alpha-adrenergic/muscarinic cholinergic pathways in the regulation of airway smooth muscle has been a popular idea. Although some evidence supports this hypothesis, direct proof of its validity has been elusive. Concepts regarding the pathobiology of asthma have shifted from a focus on changes in smooth muscle per se to the prominent inflammatory nature of this disorder. We review some of the evolving information regarding the pathogenesis of this disorder and discuss how altered neurohormonal regulation of key inflammatory cells may contribute to the asthmatic condition. PMID- 2197154 TI - Dopamine receptors and transporters in Parkinson's disease and schizophrenia. AB - The loss of midbrain dopamine in Parkinson's disease is accompanied by a matching loss in the dopamine transporter and a rise in the D1 and D2 receptor densities. This is found in the brain putamen and caudate tissues from unmedicated patients, and may account for the good early clinical response to L-dopa. Long-term L-dopa treatment reverts the receptor densities toward normal levels. Positron emission tomography (PET) data and in vitro data generally concur. In schizophrenia the density of the dopamine transporter as well as that of the D1 dopamine receptor is normal. The D2 receptor density, however, is consistently elevated in postmortem brain putamen and caudate nucleus, even in tissues from neuroleptic free or drug-naive patients. Three sets of PET and single photon emission computed tomography (SPECT) data support the postmortem findings. Early evidence indicating abnormal D2 structure as well as a reduced link between D1 and D2 warrant a detailed study of the genes for these two receptors in schizophrenia. PMID- 2197155 TI - Nicotine receptors in the mammalian brain. AB - Nicotine is a drug of abuse that presumably exerts its psychoactive effect through its interactions with nicotine binding sites in the central nervous system. Among its potential sites of action are the neuronal nicotinic acetylcholine receptors and the neuronal alpha-bungarotoxin binding sites. In this review we focus on the neuronal nicotinic acetylcholine receptors, their diversity, distribution, and functions as nicotine receptors or as mediators of synaptic transmission in the mammalian brain. We find that the complexity characteristic of the gene family encoding the subunits of these receptors is reflected both in the pattern of expression of the genes and in the pharmacological diversity of the expressed receptors. PMID- 2197156 TI - Muscular dysgenesis: a model system for studying skeletal muscle development. AB - Muscular dysgenesis, caused by an autosomal recessive lethal mutation (mdg) in mice, is characterized by an absence of contraction of skeletal muscle. A historical review of the investigation of this disorder is presented. The early studies of the morphological and physiological aspects of the disorder in vivo and in vitro presented evidence for dysfunction in the skeletal muscle excitation contraction (E-C) system, and thus suggested that skeletal muscle was the primary target of dysfunction in dysgenesis. Subsequent evidence, including the phenomenon of rescue (restoration of contraction) of dysgenic muscle in culture by spinal cord cells, argued for involvement of the nervous system in the disorder. Experiments demonstrating that dysgenic muscle lacks the slow calcium current associated with E-C coupling, and the protein (the dihydropyridine receptor) also associated with such coupling, led to the discovery of the probable site of the mutation: the gene for the alpha 1 subunit of the dihydropyridine receptor. The neuronal involvement hypothesis was further countered by several lines of evidence, including the phenomenon of fusion of nonmyogenic normal cells with dysgenic myotubes in cocultures of normal cells and dysgenic muscle. The use of the mutant as a model for studying the development of normal skeletal muscle is discussed and future avenues of research are explored. PMID- 2197157 TI - [High prevalence of obstructive lesions of the extracranial carotid arteries in reno-vascular hypertension]. AB - Ischemic stroke represents a leading cause of death in patients with renovascular hypertension. In the vast majority it is related to obstructive lesions of the extracranial tracts of the carotid arteries. Since no data were previously available on carotid artery lesions in patients (pts) with renovascular hypertension, a prospective case-control study was undertaken to assess the prevalence of carotid artery lesions in renovascular hypertension. Nineteen pts (10 females and 9 males, age: 26-77 yrs) with a diagnosis of renovascular hypertension based on the presence of uni- or bilateral renal artery stenosis and favourable outcome after either percutaneous transluminal renal angioplasty or surgery, and/or renal vein studies, were evaluated. The cause of renal artery stenosis was atherosclerosis in 12 pts and fibrodysplasia in 7. Each pt was matched with a control pt with primary hypertension for sex, race, age, blood pressure levels, smoking habits and serum cholesterol levels. Carotid artery lesions were assessed using a high resolution echo-Doppler (Duplex) system (Biosound 2000, probe 4 cm, 8 mHz). After the matching, the two groups were almost identical in terms of demographic features and risk profile. In the control group the prevalence of carotid artery lesions was similar to that reported in the literature. On the contrary, a highly significant higher prevalence of carotid artery lesions was observed in the pts with renovascular hypertension (92.1 vs 42.1%, respectively; p less than 0.001). Subgroup analysis showed that this difference was found mainly in pts with atherosclerotic renal artery stenoses.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2197158 TI - Antihypertensive activity and duration of action of dilevalol in hypertensive patients at rest and during exercise. A comparison with captopril. AB - The aim of this study was to compare the effect of dilevalol and captopril on blood pressure and heart rate in hypertensive subjects, both at rest and during bicycle exercise. Thirty mild hypertensive patients (24 men, 6 women), aged 34 55, were studied in a randomized, double-blind, parallel group trial. After a 3 week placebo run-in, patients were randomized to receive either dilevalol (200 mg once daily) or captopril (50 mg twice daily) for 4 weeks. Dilevalol-treated patients whose diastolic blood pressure had not decreased by more than 8 mmHg from baseline (or to less than 95 mmHg) were given 400 mg once daily for a further 2 weeks. Treatment was stopped for all other patients. Blood pressure and heart rate were measured at rest and during bicycle exercise tests 4 ("peak") and 24 hours ("trough") after dosing in the dilevalol group and 4 ("peak") and 12 hours ("trough") after dosing in the captopril group. At the end of the placebo run-in, mean resting blood pressure was 156/102 mmHg in the dilevalol group and 157/103 in the captopril group. Six patients had blood pressure normalization with captopril and 9 with dilevalol 200 mg; a further 2 patients achieved normalized blood pressure levels with dilevalol 400 mg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2197159 TI - [A computerized support system for the ambulatory treatment of patients with arterial hypertension]. AB - AGAPE (Computer-based Outpatients' Clinic Programme) is a programme for IBM compatible microcomputers realised by physicians for the management of hypertensive patients. The programme is planned to make the operators' work complete and expeditious while, at the same time, respecting the standard formulation of the clinical approach to the patient. The collection, organisation, recording and communication of data are handled on line by the programme under the operator's control. Special attention has been given to the control of the quality of the data collected as well as to their easy use for clinical, research and statistical purposes. This programme was used for 52 months in a hypertension clinic where physicians and nurses work jointly. Up to April 1989, 1924 new patient visits and 10,639 control visits together with 3,375 groups of lab tests were inserted. The mean training time for new operators was 3.2 hours; the mean data insertion time was 12.5 minutes for the first visit, 3 minutes for the subsequent visits and 2.5 minutes for lab tests. The drop-outs, evaluated at one-year follow-up on each 250 patients before and after the introduction of the computerized system, were 84/250 and 64/250 respectively (p less than 0.05), with a trend to wards the better control of hypertension (diastolic blood pressure less than 90 mmHg, 128/250 vs 143/250, n.s.). PMID- 2197160 TI - [Antihypertensive therapy and primary prevention of ischemic cardiopathy]. PMID- 2197161 TI - [Epidemiology of the avoidable delay in patients with acute myocardial infarct admitted to the coronary care unit]. AB - Despite the availability of safe and effective drugs for the treatment of acute myocardial infarction, nowadays, only a minority of patients arrive at the hospital early enough to receive the benefit of these treatments. The reason for this is still uncertain. Our intention was to review the literature on this topic, check if there were some issues that could be identified as delay promoters, and see if any Italian data were available, in order to make a comparison with international data. We found a substantial agreement among the Authors that median total delay (i.e. the time between the onset of symptoms and the arrival at the hospital) is between three and five hours, and it seems that this has remained fairly stable over the years. The decision delay (i.e. the time between the onset of symptoms and the first medical contact) is almost unanimously indicated as the major single component in the total delay. This represents around 40% of the pre-hospital phase. Transportation time appears to play only a slight role, if indeed any, in the total delay. Nonetheless, mobile coronary units have consistently shown that they can reduce thrombolysis time (e.g. the time between the onset of symptoms and the start of thrombolytic infusion) by almost 60 minutes, and this time-gain is comparable with the reduction in total delay obtained in Sweden with a media campaign. Strongly contrasting results were obtained from the analysis of the delay-determining factors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2197162 TI - [Research protocol for the epidemiology and clinical aspects of silent ischemic cardiopathy]. PMID- 2197163 TI - [Pregnancy in Crohn disease and ulcerative colitis. Maternal and fetal risks]. AB - Familial occurrence in chronic inflammatory bowel disease is well established. Recurrence risks for first degree relatives range from 1 to 5%. A pregnancy is usually not negatively influenced by the disease. The risks for miscarriages are slightly increased, if conception takes place during periods of inflammatory activity. In the case of first manifestation during pregnancy, however, mother and child are exposed to increased risks. The course of the disease is usually not negatively influenced by pregnancy. The rate of relapse is similar to that of comparable samples without pregnancy. In women with an active disease, the prognosis is considerably poorer. The risk to children as a result of drug therapy can be regarded as low. Family planning, pregnancy and birth entail an increased psychological demand, which, in turn, necessitates specific therapy in some cases. PMID- 2197164 TI - [A rapid test procedure for the detection of B streptococci in the perinatal period]. AB - At the Hospital of the Department of Gynaecology of the University of Heidelberg, a latex agglutination test (Strep B Patho Dx Test) was applied after extraction of antigens from amniotic fluid and gastric aspirate, parallel to the routine screening programme (vaginal and anal swabs) for maternal colonization with B streptococci. The latex agglutination test was applied in 1336 cases. Maternal vaginal colonization was detected in 14%, anal colonization in 17% of the cases. A comparison of the results obtained with the latex agglutination test and with conventional bacteriological procedures (no gradual bacteriology, incubation 48 hours) showed antigen identification in amniotic fluid in 54%, respectively 24%. In gastric aspirates a B streptococcal contamination was detected by bacteriology in 40% of cases, by the rapid latex agglutination test in 22%. If no streptococci were found in the mother, amniotic fluid or gastric aspirates were contaminated in 4% or 6%, respectively (agglutination test or bacteriology, respectively). With a sensitivity of approximately 50% and a specificity of 98%, the latex agglutination test proved superior to routine bacteriology. All clinically contaminated newborn (positive blood specimens) were clearly identified by this test. With this new latex agglutination test, a procedure is now available to detect B streptococcal contamination in newborns within less than half an hour, thus an intra- or postpartal antibiotic therapy can be applied early. PMID- 2197165 TI - [Surfactant substitution in severe respiratory distress syndrome in premature infants weighing less than 1,000 g]. AB - 19 preterm infants with severe respiratory distress syndrome (RDS) were treated with a single dose of natural porcine surfactant (Curosurf, 200 mg/kg). 9 patients had a birth weight of less than 1000 g (845 +/- 112 g, mean +/- SD and the mean gestational age was 27.2 +/- 2.1 weeks). The other 10 had a birth weight of greater than 1000 g (1521 +/- 218 g and a mean gestational age 31 +/- 2.8 weeks). Age at treatment was 3 h in infants less than 1000 g and 4 h in patients greater than 1000 g. Both groups of infants showed a rapid improvement in oxygenation and gas exchange within minutes after surfactant replacement. Exposition to greater than 60% and greater than 40% oxygen was identical in both groups. However, time in greater than 21% oxygen was significantly longer in infants less than 1000 g (median 30 days, 8.5 days in patients greater than 1000 g, p less than 0.01). The duration of mechanical ventilation was 33 days, in patients greater than 1000 g and 5 days; p less than 0.01. None of the infants developed a pneumothorax, but 6 out of 9 patients less than 1000 g developed mild bronchopulmonary dysplasia. 2 infants less than 1000 g died at day 5 and day 11 from cardio-circulatory arrest following ligation of a patent ductus arteriosus, and nosocomial septicaemia, respectively. Prolonged mechanical ventilation and exposure to oxygen in patients less than 1000 g cannot be attributed to surfactant deficiency alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2197166 TI - [Cultural and serologic Chlamydia detection in diagnosis of sterility and increased risk of infection]. AB - 364 women were studied for the possible role of chlamydia trachomatis infection as a factor related to infertility. C. trachomatis was isolated from the cervix in 20% of our high-risk STD patients and in a much lower proportion in patients with tubal (5%) or unexplained (4%) infertility. IgG-antibodies to C. trachomatis were found in 75% of patients with tubal infertility, in 44% of women without gynaecological diseases and in 87% of the high-risk STD patients. By contrast, the difference was significant in the IgA-antibody tests. 67% of the women with tubal infertility and only 25% of the women with nontubal infertility were positive. From these data it appears, that antecedent infections with C. trachomatis, as measured by antibody prevalence, are an important factor in infertility of tubal origin. PMID- 2197167 TI - [Vaginal sonography: pilot study for using in ovarian screening procedures]. AB - From May to September 1987, 221 women of over 45 years of age were examined by transvaginal ultrasound at the Department of Gynaecology (Gynaecological Hospital) of the University of Marburg. Transvaginal ultrasound proved to be significantly superior to clinical examination, since palpation had resulted in "NAD" findings in all cases. The average diameter and the volume of postmenopausal ovaries, determined by transabdominal sonographic studies, were easily confirmed by the new method. In 6% of the 221 patients, pathological findings of the ovaries were clinically "NAD". Since the usefulness of transabdominal ultrasound in screening for ovarian cancer has already been confirmed by other authors, this pilot study aims at providing an opportunity to test transvaginal ultrasound also in a large ovarian cancer screening programme by furnishing the essential basic research data. Age-adapted average ovarian sizes and significant differences in size between the right and the left ovary were used to differentiate between normal and pathological findings as well as changes in the ovarian parenchymal patterns. PMID- 2197168 TI - [Doppler examination as an indication for surgical delivery. A case report]. AB - Pathological alterations in foetoplacental circulation can lead to zero flow or even to reverse flow in the diastole. In these cases, a high fetal risk can be expected. Based on our Doppler measurements, we recommend by zero flow in the umbilical artery or foetal aorta, that the childbirth could be postponed under an observant attitude using intensive controls (CTG, foetal movements), but pregnancy has to be terminated immediately by Caesarean section at the first sign of reverse flow. PMID- 2197169 TI - [Monoclonal antibodies: immunobiotechnologic principles of production and prospects of use]. PMID- 2197170 TI - Effect of crown preparation height on the retention and resistance of gold castings. PMID- 2197171 TI - Amalgam repair: an in vitro evaluation of bond integrity. PMID- 2197172 TI - Comparison of microleakage between direct placement composites and direct composite inlays. PMID- 2197173 TI - [The problem of the adaptive norm in human populations]. AB - The results of some investigations recently fulfilled in the framework of population-genetics approach to the problem of adaptive norm in human populations are summarized in this review. The main items considered are: methods of identification of morphologically "average" phenotypes, the role of stabilizing selection in maintaining the population adaptive norm, the problem of joint variation of monogenic and polygenic traits ant its relevance to "norm" and pathology. The significance of the concept of adaptive norm for preventive medicine and genetic monitoring is discussed. PMID- 2197175 TI - Symmetric lac operator derivatives: effects of half-operator sequence and spacing on repressor affinity. AB - We have analyzed lac repressor binding in vivo and in vitro to several symmetric lac operator sequences. Two features of the operator appear to be important for repressor binding: sequence, both of the operator and of its extended regions, and the spacing of the operator halves. Host mutations that alter DNA superhelical density (topA, gyrB) did not change the relative affinity of cloned symmetric operator sequences for repressor. Analysis by dimethylsulfate methylation and DNaseI digestion of repressor-operator complexes indicated that repressor makes symmetric contacts with the symmetric operator, in contrast to its contacts with the two halves of the natural operator. PMID- 2197174 TI - [Cloning of the RIB1 gene coding for the enzyme of the first stage of flavinogenesis in the yeast Pichia guilliermondi, GTP cyclohydrolase, in Escherichia coli cells]. AB - The RIB1 gene encoding the enzyme of the first stage of the yeast Pichia guillermondii-GTP-cyclohydrolase- was cloned on pFL38 shuttle vector as the Sau3A fragment of chromosomal DNA of about 9 kb. EcoRI fragment of 4 kb with RIB1 gene was subcloned from the pFRI hybrid plasmid obtained into the pUC18 plasmid and then shortened to give 2.9 kb via deletion in SalGI site. The plasmid constructed was designated pR1. Activity of GTP-cyclohydrolase was 80-100-fold higher in extracts of transformants than in the prototroph strain, which evidence of effective expression of the yeast gene within recombinant plasmids in the cells of this species of bacteria. The enzyme isolated from transformants has molecular mass 179 kDa, is inhibited by PAD and adenyl-nucleotides, which is characteristic of GTP-cyclohydrolase of P. guilliermondii but not of Escherichia coli. PMID- 2197176 TI - Blunt-end and single-strand ligations by Escherichia coli ligase: influence on an in vitro amplification scheme. AB - A ligase-based, in vitro DNA amplification system (LAR) has been described by Wu and Wallace [Genomics 4 (1989) 560-569]. This strategy is based on the ability of a DNA ligase to join the 5' phosphate of one DNA molecule to the 3' hydroxyl of a second during a nick-closing reaction. Escherichia coli DNA ligase has been used in place of the T4 DNA ligase in our study in order to limit template-independent ligation activities, which lower the sensitivity of this amplification procedure. The results of this study indicate that E. coli ligase also joins blunt-ended DNA molecules and some single-stranded oligodeoxyribonucleotides, in the absence of a complementary template, with an efficiency which is sensitive to both the concentrations of DNA substrate and enzyme. PMID- 2197177 TI - Expression of cloned restriction and modification genes, hjaIRM from Hyphomonas jannaschiana in Escherichia coli. AB - A type-II RM system, HjaI, was identified in the marine bacterium, Hyphomonas jannaschiana. The ENase recognizes GATATC, and DNA fragments generated after cleavage with this enzyme contain blunt ends. A DNA fragment encoding these enzymes was cloned and expressed in Escherichia coli, although the level of expression of the cloned genes was low. DNA methylated by M.HjaI was not restricted by the Mcr or Mrr restriction systems of E. coli. Although H. jannaschiana is a marine bacterium isolated near the thermal vents on the floor of the Pacific Ocean, the biochemical properties of the ENase were similar to those of EcoRV, an isoschizomer isolated from E. coli. PMID- 2197178 TI - Requirement of integration host factor (IHF) for growth of Escherichia coli deficient in HU protein. AB - Escherichia coli mutants deficient in histone-like protein, HU, and integration host factor (IHF) were constructed and their growth characteristics were examined. Mutants deficient in both HU and IHF grew slowly and were filamentous at both 30 degrees C and 37 degrees C. These mutants scarcely grew in LB broth at 42 degrees C. They formed minute colonies on LB plates at 42 degrees C and no colonies at 46 degrees C, indicating temperature-sensitive (ts) growth. On the contrary, mutants deficient in either HU or IHF were not ts for growth. These results indicate that IHF compensates for the absence of HU and permits normal cell growth; this suggests functional similarity between HU and IHF. PMID- 2197179 TI - Heterogeneity among the 2 microns plasmids in Saccharomyces cerevisiae: a new sequence for the REP1 gene. AB - Some species of yeasts contain naturally-occurring circular DNA plasmids. The most studied of these plasmids is the 2 microns circle of Saccharomyces cerevisiae. Three variants of this plasmid, Scp1, Scp2 and Scp3, have been described according to their restriction maps [Cameron et al., Nucleic Acids Res. 4 (1977) 1429-1448; Livingston, Genetics 86 (1977) 73-84]. The entire nucleotide (nt) sequence of the Scp1 variant from strain A364A has been published [Hartley and Donelson, Nature 286 (1980) 860-864]. We report here the nt sequence of the 2 microns plasmid REP1 gene from S. cerevisiae strain SKQ2n. According to the restriction analysis, this plasmid is the Scp3 variant previously described. The only observed differences between the Scp1 and Scp3 variants were the loss of one EcoRI restriction site and an apparent deletion in Scp3. The nt sequence we report differs significantly from the previously published one for Scp1. The differences correspond to 128 (about 8.5%) substituted, deleted or additional nt of 1510 nt compared. These differences affect the coding region (8%) as well as the noncoding regions (9.7%). Regarding the putative encoded proteins, 38 (about 10%) amino acids (aa) are modified or deleted in our sequence and 11 are added. Most of these aa modifications are not randomly distributed but are concentrated in certain regions. These observations are indicative of important intraspecific evolution between the two 2 microns plasmid variants considered, as well as of conservative selection pressure on some domains of the REP1 protein. PMID- 2197180 TI - Identification of a seventh operon on plasmid RK2 regulated by the korA gene product. AB - Broad-host-range IncP plasmids possess a series of operons involved in plasmid maintenance, whose expression is coordinated by a series of regulators, most of which are encoded in a central regulatory operon. The nucleotide sequence of a new monocistronic operon located between coordinates 55.0 and 56.0 kb on the genome of the IncP alpha plasmids RK2 and RP4 is presented. The operon encodes a 34 kDa protein which has a net negative charge. Transcription of the operon, designated by us kfrA (korF-regulated), is repressed not only by the product of the previously described korA gene but also by the product of a gene which we have designated korF and which has not been described previously. The korF gene is encoded downstream from korB within the key korA/korB regulatory operon. We propose that K or F binds to a novel inverted repeat overlapping the promoter for the kfrA operon. PMID- 2197181 TI - Expression in Escherichia coli of two mutated genes encoding the cholera toxin B subunit. AB - To allow subsequent genetically mediated fusion of foreign antigens to cholera toxin B subunit (CTB), two mutated CTB encoding genes (ctxB) were constructed and overexpressed in Escherichia coli. The signal peptide coding sequence was deleted and restriction sites were created at both ends of the modified sequence. Both synthesized CTBs contain additional amino acid(s) at the N terminus (one and three). They were purified as insoluble products and refolded into the natural pentameric CTB structure by a denaturation-renaturation cycle. After renaturation, both recombinant proteins recovered CTB antigenicity and the ability to bind to GM1 gangliosides, as shown by in vitro analysis. Preliminary data indicated that both properties were unaltered by fusion of a foreign peptide to the mutated CTBs. PMID- 2197182 TI - Nucleotide sequence and deletion analysis of the cellulase-encoding gene celH of Clostridium thermocellum. AB - The complete nucleotide sequence of the celH gene of Clostridium thermocellum was determined. The open reading frame extended over 2.7-kb DNA fragment and encoded a 900-amino acid (aa) protein (Mr 102,301) which hydrolyzes carboxymethylcellulose, p-nitrophenyl-beta-D-cellobioside, methylumbelliferyl- beta-D-cellobioside, barley beta-glucan, and larchwood xylan. The N terminus showed a typical signal peptide, and a cleavage site after Ser44 was predicted. Two Pro-Thr-Ser-rich regions divided the protein into three approximately equal domains. The central 328-aa region was similar to the N-terminal part, carrying the active site, of C. thermocellum endoglucanase E (EGE; 30.2%). The C-terminal region ended with two conserved 24-aa stretches showing close similarity with those previously described in EGA, EGB, EGD, EGE, EGX, and xylanase from C. thermocellum. Deletions of celH removing up to 327 codons from the 5' end and up to 245 codons from the 3' end of the coding sequence did not affect enzyme activity, confirming that the central domain was indeed responsible for catalytic activity. Production of truncated EGH in Escherichia coli was increased up to 120 fold by fusing fragments containing the 3' portion of the gene with the start of lacZ' present in pTZ19R. PMID- 2197183 TI - Recombinant RNA polymerase: inducible overexpression, purification and assembly of Escherichia coli rpo gene products. AB - The genes, rpoA, rpoB and rpoC of Escherichia coli, which encode the RNA polymerase alpha-, beta- and beta'-subunits, respectively, have been individually placed on expression plasmids under the control of the bacteriophage T7 promoter. Induction of the T7 RNA polymerase gene in host cells harboring each of the three plasmids resulted in the extensive overproduction of the three polypeptides. The overproduced subunits were purified and assembled into a functional enzyme, whose specific activity and dependence on the sigma-factor were indistinguishable from native RNA polymerase purified by conventional methods. PMID- 2197184 TI - Expression of a yeast glycolytic gene is subject to dosage limitation. AB - The Saccharomyces cerevisiae pyruvate kinase-encoding gene (PYK1) has been transformed back into yeast using a derivative of the multicopy vector, pJDB207. High levels of PYK1 expression in these transformants are limited by at least two separate mechanisms. Pyruvate kinase assays and polysome analyses demonstrate that the translation of the PYK1 mRNA is inhibited as its abundance increases. The abundance of the PYK1 mRNA per gene copy also decreases as the copy number of the PYK1 gene increases. This is the first report which demonstrates that a eukaryotic glycolytic gene is subject to dosage limitation at the translational level. PMID- 2197185 TI - Cloning of the yeast SFL2 gene: its disruption results in pleiotropic phenotypes characteristic for tup1 mutants. AB - We have identified a yeast gene, SFL2 (suppressor gene for flocculation), which complemented a newly isolated sfl2 mutant. This mutation causes asexual cell aggregation. The strain bearing the SFL2 gene disruption exhibited pleiotropic phenotypes characteristic for tup1 mutants. Physical mapping and complementation analysis suggested that the cloned SFL2 gene is identical to the TUP1 gene. The SFL2 gene encodes a 669-amino acid protein which has domains rich in glutamine, as does the SSN6 protein. PMID- 2197186 TI - The essential region for assembly and particle formation in hepatitis B virus surface antigen produced in yeast cells. AB - The hepatitis B virus (HBV) genome carries a HBV surface antigen (HBsAg) gene that can encode a polypeptide of 226 amino acids (aa). This gene can be expressed in the yeast, Saccharomyces cerevisiae, and the products can be assembled into 22 nm particles indistinguishable from those recovered from a patient's serum. We constructed a set of deletion derivatives of the HBsAg gene, and examined the particle-forming ability of the resulting polypeptides by expressing the gene in yeast. Elimination of 9 aa from the N terminus had no effect, whereas the elimination of 21-80 aa decreased the ability to form particles, and the particles formed were correspondingly smaller. Elimination of 100 aa that delete the major hydrophobic domain of the molecule abolished the ability to form particles completely. Deletion of 53 aa from the C terminus showed little effect. However, deletions proceeding further toward the center of the molecule rendered the polypeptides unstable. PMID- 2197187 TI - Identification of a novel alpha-amylase by expression of a newly cloned human amy3 cDNA in yeast. AB - A novel amylase gene (amy3) that differs in nucleotide sequence from salivary amylase gene (amy1) and pancreatic amylase gene (amy2) has been described [Tomita et al., Gene 76 (1989) 11-18], but whether this gene can ever code for an active enzyme has not been shown. We prepared cDNA of this gene from an mRNA obtained from lung carcinoid tissue, and expressed it in Saccharomyces cerevisiae under the control of an acid phosphatase promoter. The product was secreted into culture media, and showed enzymatic activity, demonstrating that this novel alpha amylase gene (amy3) can code for a functional isozyme. We purified this enzyme, and compared its biological properties with those of salivary and pancreatic human amylases similarly expressed in yeast. We observed that the novel amylase isozyme is more heat-sensitive than others, and that its substrate specificity is different from the other two isozymes. PMID- 2197188 TI - [Embryotoxic and teratogenic effects of alkaline protease and a synthetic enzyme containing detergent]. PMID- 2197189 TI - [Use of cell culture for the assessment of pathogenicity of destructive microorganisms]. PMID- 2197190 TI - [Approbation of biological tests for control of sterilization]. PMID- 2197191 TI - [Experiences with a new microvascular anastomosis. Experimental studies in the rat]. PMID- 2197192 TI - [Regeneration of taste buds following injury of the lingual nerve]. PMID- 2197193 TI - [Results of microsurgery of sensory peripheral branches of the mandibular nerve]. PMID- 2197194 TI - [Possibilities for microsurgical reconstruction of the facial nerve]. PMID- 2197195 TI - [Imaging procedures as principle aids in functional surgical therapy of the temporomandibular joint]. PMID- 2197196 TI - [Historical development and current status of microvascular surgery]. PMID- 2197197 TI - [Role of monitoring in microvascular or vascular pedicled tissue transfer]. PMID- 2197198 TI - [Angiodynography: a noninvasive procedure for planning and follow-up of microsurgical anastomosis of transplants]. PMID- 2197199 TI - [Microsurgical soft tissue transfer in the area of the mouth-jaw-face]. PMID- 2197200 TI - [Problems and experiences in microsurgical replantation of complete forehead, scalp and neck scalping]. PMID- 2197201 TI - [Anterior tooth trauma--the endodontic aspects]. PMID- 2197202 TI - [Comparative studies of the prognosis of supporting areas]. AB - After measuring average supporting zones in the deciduous and permanent dentition the "leeway space" is determined. The prognostic value of three methods is compared with the average supporting zones in the eugnathic permanent dentition. Separate measurements for the upper and lower jaw in the male and female were done. Correlations between early erupted teeth were considered in the prognosis of the size of the supporting zones. Prognostic values differ, they could be smaller, of equal size or larger compared with the average supporting zones. Average discrepancies range from 0 mm to 1.04 mm. Individual differences are larger amounting up to 3.24 mm. The average differences, but not the individual ones are probably only relevant in important clinical areas. PMID- 2197203 TI - Reminiscences of the first FSMFN graduate: a nurse called Mitch. PMID- 2197204 TI - Chronic pancreatitis. PMID- 2197205 TI - Pancreatic resections for chronic pancreatitis. PMID- 2197206 TI - Venous, biliary, and duodenal obstruction in chronic pancreatitis. PMID- 2197207 TI - Advances in diagnosis and management of hydatid disease. AB - Over the last decade substantial improvements have been made in the diagnosis and management of hydatid disease. New diagnostic tests, imaging procedures including ultrasonography, computerized tomography, magnetic resonance and ERCP. Until recently the only definitive treatment for hydatid disease has been surgery, which carries high morbidity, mortality and recurrence. Advances in drug therapy has been influenced by the introduction of Albendazole. In our own study, Albendazole was administered to 22 patients with hydatid disease of the liver, and encouraging results were achieved in most of the patients. Another recent improvement has been the introduction of a non-surgical endoscopic method for the management of biliary and liver echinococcus. In 1985 we published the first report on the use of this procedure. The fourth recent aspect of treatment is the percutaneous aspiration and drainage of hydatid cyst of the liver. These recent developments, used either alone or in combination, are, we believe, good potential alternatives to operative surgery that carry a smaller incidence of complications, morbidity and mortality. PMID- 2197208 TI - Improved survival after prophylactic portal nondecompression surgery for esophageal varices: a randomized clinical trial. Cooperative Study Group of Portal Hypertension of Japan. AB - To evaluate prophylactic surgery for esophageal varices, a prospective randomized controlled trial was begun in 1980 by the Japanese Research Society for Portal Hypertension. Methods of operation included selective shunts and nonshunting interruption procedures. One hundred and twelve Japanese patients, in whom endoscopic findings suggested risk of bleeding but who had no bleeding episode, were randomly allocated to the operated group of 60 patients or nonoperated group of 52 patients. Nine patients with idiopathic portal hypertension, histologically proven noncirrhotic disease, which all fell in the operated group, were excluded from the study and the remaining 103 patients (51 operated and 52 nonoperated) were analyzed. Long-term follow-up of patients for a median of 49 mo with a maximum of 73 mo showed a total of 11 (22%) deaths, including 2 operative deaths, in the operated group compared with 23 (49%) deaths in the nonoperated group. The cumulative survival rate at 5 yr in the operated group was 72%, which was significantly higher than the 45% of the nonoperated group (p less than 0.05). The cumulative variceal bleeding rate at 5 yr was 7% in the operated group, which was significantly lower than that of the nonoperated group of 46% (p less than 0.001). It was concluded that portal nondecompression surgery was effective in preventing the variceal bleeding and in improving survival. PMID- 2197209 TI - Renal and systemic hemodynamics in experimental cirrhosis in rats: relation to hepatic function. AB - The onset of sodium retention in the phenobarbital and carbon tetrachloride model of cirrhosis in the rat is preceded by a linear decrease in hepatic function as measured by the aminopyrine breath test. Sodium retention occurs when liver function decreases below a critical threshold. Changes in systemic hemodynamics may be responsible for initiating the development of renal sodium retention. The objective of this study was to investigate the relationship between hepatic function and systemic and renal hemodynamics of experimental cirrhosis in rats maintained on a constant salt diet. Cirrhosis was induced in phenobarbital treated rats by weekly administration of carbon tetrachloride. The aminopyrine breath test served as a measure of hepatic function. Three groups of animals were studied to evaluate the contribution of changes in systemic and renal hemodynamics to the onset of sodium retention: a group with sodium retention and aminopyrine breath test results just below the critical threshold, a group without sodium retention and aminopyrine breath test results just above the critical threshold and a phenobarbital-treated control group. In each group, urinary sodium excretion, renal plasma flow, glomerular filtration rate, mean arterial pressure and arterial and renal venous plasma renin activities were determined. A progressive, significant reduction in mean arterial pressure was seen, comparing controls with the other two groups. No differences in renal plasma flow were observed between the three groups, but glomerular filtration rate and filtration fraction were slightly reduced in the sodium-retaining group compared with the non-retaining group and controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2197210 TI - Why is prophylactic portal nondecompressive surgery effective in preventing hemorrhage from esophageal varices? PMID- 2197211 TI - Ursodeoxycholic acid in the treatment of primary biliary cirrhosis: first controlled data. PMID- 2197212 TI - The demography of primary biliary cirrhosis in Ontario, Canada. AB - The demographics of primary biliary cirrhosis in Ontario, Canada, are described. Two hundred and twenty-five primary biliary cirrhosis patients were identified by 85 of 502 gastroenterologists (or internists) practicing in Ontario acute care hospitals that have 150 or more beds. Two hundred and six patients were verified as being antimitochondrial antibody-positive, resulting in an incidence of 3.26 per million per year and a prevalence of 22.39 per million. Questionnaire data were obtained on 88.5% of these patients. Twenty-nine percent of the patients were found to be asymptomatic. Geographical clustering and racial predisposition were not seen. No increase in breast cancer prevalence was noted. By the time the diagnosis of primary biliary cirrhosis was established, the patients had consulted a median number of 3.5 physicians. Fatigue was reported as the most disabling symptom. The diagnosis of primary biliary cirrhosis in patients referred from across the province of Ontario was independently confirmed by us, using standard criteria (antimitochondrial antibody testing and liver biopsy), and was found to be reliable. PMID- 2197213 TI - CEOs: keep capital fold-in out of budget politics. AB - Hospital CEOs don't want to see Medicare capital reimbursement fall victim to budget politics. Yet, that's likely to happen if the Health Care Financing Administration folds capital reimbursement into the prospective pricing system (PPS), CEOs say. Moreover, the majority of CEOs say that no fair method of including capital payments in PPS rates can be developed. PMID- 2197214 TI - Cyclophosphamide- and testosterone-induced alteration in chicken bursal stroma identified by monoclonal antibodies. AB - Both cyclophosphamide (Cy) and testosterone propionate (TP) treatments ablate B cells in chickens. Essential bursal microenvironmental elements, however, are altered or lost following TP treatment, while bursae from Cy-injected birds can be reconstituted with donor precursors. These two models can thus be utilized to distinguish which bursal stromal molecules are functionally most important in the specific microenvironment of this organ. Monoclonal antibodies (mAb) reactive with non-lymphoid components of the chicken bursa of Fabricius have been used to examine bursal sections from birds treated with Cy or TP. Molecules have been identified on the epithelial buds and follicle-associated epithelium (FAE) that are enhanced following Cy treatment (MUI-52 and 58) and are absent in TP-treated birds. The expression of these molecules may correspond to the ability of Cy treated but not TP-treated bursae to attract lymphoid precursors. Molecules have also been identified on cells in the subepithelial mesenchymal layer (MUI-63, 65 and 75). These cells interact with the surface epithelium (sEp) prior to epithelial bud formation, an interaction which appears to be TP sensitive. Additionally, two potentially important molecules have been identified in the bursal medulla (MUI-54 and 72) which may have an interactive role with developing B lymphocytes. PMID- 2197215 TI - T cells do not mediate the initial suppression of a Salmonella infection in the RES. AB - The course of a sublethal salmonella infection was followed in mice rendered susceptible by irradiation, reconstituted with T-cell-depleted bone marrow from normal donors and given a synergistic pool of CD4 and CD8 monoclonal antibodies. The results indicate that the host response causing the early plateau and suppression of bacterial growth at the end of the first week of the infection, which is essential for survival, does not require T cells. PMID- 2197216 TI - Granulocyte-macrophage colony-stimulating factor and interleukin-3 induce surface expression of interleukin-2 receptor p55-chain and CD4 by human eosinophils. AB - In this report it is shown by immunofluorescence analysis, biochemical analysis and mRNA hybridization that human eosinophils express surface CD4 and interleukin 2 receptor (IL-2R) (CD25) when exposed to eosinophil activators granulocyte macrophage colony-stimulating factor (GM-CSF) and IL-3. Although the functional role of eosinophil CD4/CD25 expression has to be elucidated, it will be of interest in further studies to investigate whether in vivo induction of these molecules occurs in association with certain disease processes such as the hypereosinophilic syndrome or in immunological responses during allergic and helminthic parasitic diseases. PMID- 2197217 TI - A novel monoclonal antibody, Mar 1, directed specifically against mononuclear phagocyte system cells in rats. AB - Three different monoclonal antibodies (mAb), designated Mar 1, Mar 2, and Mar 3, recognizing three distinct novel antigen molecules expressed preferentially in rat macrophages, were produced by the hybridoma technique. Binding of these mAb to isolated cells or fixed cells was detected by radioactive binding assay, immunohistochemical technique and flow cytometry. Mar 1 binds specifically to the cells constituting the mononuclear phagocyte system (MPS), but not to granulocytes nor endocytosis-positive cells from non-lymphoid tissues. Mar 2 and Mar 3 recognize both the former and the latter. The isotypes of Mar 1, Mar 2 and Mar 3 were defined as IgG1, IgG1 and IgG2b, respectively. These mAb were species specific, allo-non-specific and not cytotoxic for rat peritoneal macrophages. Immunoelectron microscopic observation demonstrated that Mar 1-3 antigens are located on both surface membrane and cytoplasmic membrane structures of peritoneal macrophages, particularly on the limiting membrane of phagocytic small vesicles and large phagosomes. Immunoprecipitation experiments demonstrated that the apparent molecular weights (MW) of the reactive antigens of Mar 1, Mar 2 and Mar 3 are 95,000, 100,000 and 55,000 and 27,000, respectively. These findings indicate that all of Mar 1-3 mAb have considerable value in the identification of rat phagocytes and that, of the three kinds of antigens detected with Mar 1-3, Mar 1 antigen is a specific marker for identification of the cells constituting the MPS and may offer the means to assess the functional capability and differentiation process of the macrophage populations. PMID- 2197218 TI - Demonstration and phenotypic characterization of resident macrophages in rat skeletal muscle. AB - Using immunohistochemical techniques and a panel of murine monoclonal antibodies that recognize rat cells of the mononuclear/phagocyte lineage, it has been demonstrated that the cells labelled with these antibodies are widely distributed throughout the perimysial and endomysial sites in the rat skeletal muscle. These cells have a distinctive dendritic morphology and form phenotypically heterogenous populations. Double immunoperoxidase staining with the monoclonal antibody and anti-Von Willebrand factor antiserum, which recognize vascular endothelial cells, revealed that most of these resident macrophages are closely associated with microvasculature. The perivascular location of these cells suggests that at least some of the resident macrophages may be pericytes. These observations indicate that the macrophages form an important component of the non muscle cell population in the muscle tissue, and may be intimately involved in various immunopathological conditions of the skeletal muscle. PMID- 2197219 TI - Interleukin-6: historical background, genetics and biological significance. AB - Interleukin-6 (IL-6) is a pleiotropic cytokine previously known as B cell stimulatory factor (BSF-2), interferon-beta 2 (IFN-beta 2), 26-kDa protein, and hepatocyte stimulating factor (HSF). The name IL-6 was proposed when the nucleotide sequences of the cDNAs for these proteins had been determined and the molecules were found to be identical. IL-6 production can be induced by a wide variety of agents in a wide range of cells, although IL-6 gene expression seems to be regulated in a tissue and stimulus specific manner. At least 3 different signal pathways regulate IL-6 gene expression, emphasizing its multiply inducible nature. The currently known activities of IL-6 include regulatory functions in hematopoiesis, immune reactions and acute phase responses. IL-6 appears to be a key member of the IL family; however, it is still poorly understood how IL-6 interacts with other lymphokines within the network. The anti-viral activity of IL-6 seems to be negligible. Elevated IL-6 levels have been found in diseases like rheumatoid arthritis, multiple myeloma and systemic lupus erythematosus. The abnormal expression and dysregulation of IL-6 in certain disorders may be a typical feature of this cytokine, making it the first cytokine that may be directly related to pathogenesis. PMID- 2197220 TI - Early induction of anti-double-stranded DNA antibodies in lupus-prone MRL mice inoculated with Ly-24+ cells cloned from lymph node cells of an MRL/Mp-lpr/lpr mouse: possible effect of putative cytokines produced by cloned Ly-24+ cells. AB - We have reported that a cell line, KML1, obtained from lymph node cells of a 16 week-old female MRL/Mp-lpr/lpr (MRL/1) mouse produces a soluble factor(s) that promotes formation of anti-single-stranded (ss) DNA antibodies by cultures of spleen cells from old MRL/l mice (greater than 16 weeks old). Detailed examination revealed that KML1-7 cells cloned from the cell line KML1 were only positive for the Lys-24 (Pgp-1) phenotype, and were negative for other typical phenotypes tested, such as Thy-1, Ly-1, Ly-2, Ly-4 (L3T4) and Ly-5 (B220). This finding suggested that this line was of prothymocyte or myeloid cell lineage. From day 70 after subcutaneous inoculation of KML1-7 cells into 10-week-old MRL/Mp(-)+/+(MRL/n) mice, IgG anti-dsDNA antibodies began to replace IgM anti dsDNA antibodies in the serum of these mice, but anticardiolipin, anti trinitrophenyl hapten (TNP) and anti-poly(ADP-ribose) antibodies did not increase significantly. The predominant subclasses of anti-dsDNA antibodies that increased were IgG2a and IgG2b. IgG anti-dsDNA antibodies also became detectable as early as day 22 after inoculation of KML1-7 cells into MRL/l mice of 10 weeks old. The finding that in MRL/n mice the IgM isotype was increased first and was soon replaced by the IgG isotype was consistent with findings when spleen cells from MRL/n mice of 20 weeks old primed with ssDNA were cultured in the presence of conditioned medium containing a putative cytokine(s) (PC) produced by KML1-7 cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2197221 TI - An avian B-lymphocyte protein associated with beta 2-microglobulin. AB - A member of the family of beta 2-microglobulin (beta 2m)-associated cell surface glycoproteins was identified by the CB3 monoclonal antibody. The Mr 50,000 heavy chain of the CB3 antigen differs from conventional class I heavy chains (Mr 45,000) in the extent of glycosylation, charge, and peptide composition. Because of its selective expression on avian B cells and its similarity to mammalian class I-like molecules, we speculate that the CB3 antigen may play a role in T- and B-cell interactions, PMID- 2197222 TI - Review of available trials of selective decontamination of the digestive tract (SDD). AB - Eighteen studies on Selective Decontamination of the Digestive Tract (SDD) have been published up to now. A statistically significant reduction of infection rate was found in fourteen out of the fifteen controlled studies. Although all the studies were designed to evaluate infection-related morbidity as the end point, ten centres have reported fatality rates. Six centres out of the ten showed a statistically significant reduction in mortality in patients receiving SDD versus control. A recent French study describes the eradication of an outbreak of a multi-resistant Klebsiella with SDD. The Paris trial suggests a major impact of the SDD maneuver on the ICU ecology. Emergence of resistance to the SDD agents among gram-positive cocci has been described, although the clinical impact of this antibiotic side effect has not been reported so far. There are three indications for SDD, as follows: (i) trauma patients; (ii) liver transplant recipients and (iii) outbreaks of multi-resistant organisms. PMID- 2197223 TI - [Arterial oxygen status as a limiting factor in hemodilution]. AB - Normovolemic hemodilution under normoxic conditions (arterial oxygen partial pressure normal) at rest is limited by the critical arterial oxygen content of about 10 ml/dl corresponding to a hemoglobin concentration of 7.5 g/dl. This critical oxygen content is derived from the arteriovenous oxygen difference of the myocardium, assumed that the coronary blood flow is increased by 33% and the available oxygen is utilized nearly totally. Furthermore, stored blood (blood bag) seems to be of minor therapeutic effect because of the left shifted oxygen content curve combined with a reduced effective Hb concentration. PMID- 2197224 TI - [Myocardial oxygen supply in hemodilution in patients with healthy hearts and heart surgery patients]. AB - Infusion of colloid solutions for intentional isovolemic hemodilution can help to save homologous blood in surgical patients. In addition, hemodilution improves blood fluidity which leads to an increased organ blood flow and better tissue oxygenation. A major limiting factor for the degree of dilutional anemia induced by hemodilution is the oxygen supply of the myocardium since unimpaired heart function is of utmost importance. The basic mechanism that compensates for the reduction of hemoglobin-concentration (fall of oxygen capacity) of the diluted blood is a rise in cardiac output and coronary blood flow which maintains or even enhances systemic and coronary oxygen transport capacity (hemoglobin concentration x saturation x cardiac output or coronary blood flow). In normovolemic patients with unimpaired cardiac function there is no problem in this respect and clinical experience has shown that even high degrees of dilutional anemia are well tolerated. Patients with heart disease, however, may have a limited ability to increase cardiac output and coronary blood flow. Therefore, in these cases the risks of intentional hemodilution can exceed its benefits and a careful evaluation of risks is mandatory for every individual patient. In the following, we review knowledge from the literature and our own experimental and clinical data to explain the influence of dilutional anemia on the physiology and pathophysiology of myocardial oxygen supply. PMID- 2197225 TI - [Hypovolemic-hemorrhagic shock. Pathophysiology and therapy]. AB - The common features of all different kinds of circulatory shock are a disturbance of the microcirculation and an imbalance between cellular oxygen demand and supply. The pathophysiology is discussed by the example of hypovolemic hemorrhagic shock, including macrocirculation, humoral regulatory mechanisms, the role of vascular endothelium, and cellular dysfunction. The first aim of therapeutic efforts is the rapid restitution of a normal circulatory volume as a basic requirement for the normalisation of the microcirculation. Actual concepts of volume substitution and transfusion therapy are presented. PMID- 2197226 TI - [Perioperative blood coagulation therapy and diagnosis]. AB - The risks and adverse reactions of fresh frozen plasma (FFP) and coagulation components have changed considerably in the last few years because of the spread of HIV on the one hand, and the advances in preparation and sterilisation of the coagulation components on the other hand. Therefore, the indication for FFP and the various coagulation components deserves permanent consideration. FFP is still the therapeutical means of choice for the treatment of acquired (complex) plasmatic coagulation disorders, even though the (still) small risk of virus transmission in Middle Europe has to be taken into account. Coagulation components are primarily indicated in congenital (isolated) plasmatic coagulation disorders. Only in gross or very acute acquired coagulation disorders are coagulation components needed in addition to FFP. The same regimen is recommended for the use of antithrombin III (AT III) concentrates. In cases of acquired antithrombin deficiency, antithrombin III substitution is indicated only when the anticoagulation by heparin alone or in combination with FFP is insufficient or when the heparin dose required might cause an unacceptable bleeding risk, e.g. in simultaneous thrombocytopenia. Then AT III becomes an important therapeutic agent, especially in DIC. In addition, information regarding a rational and economic substitution of FFP and coagulation components is given, and other substitutes are mentioned which could possibly be used with less risk. Finally, the necessity of accurate diagnosing is emphasized. Close cooperation between the physicians in the clinics and in the department of transfusion medicine/hemostaseology reduces unnecessary and inadequate application of coagulation components. This also means an improvement in the patient's therapy. PMID- 2197227 TI - Electroencephalography for epilepsy surgery. PMID- 2197228 TI - The use of electroencephalography in carotid endarterectomy. PMID- 2197229 TI - Short-latency auditory evoked potentials: intraoperative applications. PMID- 2197230 TI - Somatosensory evoked potentials. PMID- 2197231 TI - Monitoring of flash visual evoked potentials during neurosurgical operations. AB - In summary, our results suggest that flash VEP monitoring is not specific for visual acuity and has not proved helpful as an intraoperative warning system. The future challenge will be to devise a method which activates only those fibers specific to visual acuity and which provides reproducible and reliable information quickly enough that adjustments in patient management can be made. PMID- 2197232 TI - Motor evoked potentials. PMID- 2197233 TI - Neurosurgical applications for intraoperative stimulation. AB - Intraoperative neurostimulation can be most useful to the surgeon whenever the need arises to assess physiological function or identify fiber pathways and/or neuronal populations in critical areas of brain, spinal cord, or peripheral nerve. Low-level (threshold) stimulation allows for the nearest populations of axons or neuronal cell bodies (in the vicinity of the electrode tip) to be activated in the safest possible fashion. When motor pathways are being tested, attention must be paid to the control and administration of muscle relaxant drugs, which can dampen or abolish muscle responsiveness during stimulation. Peripheral nerve conduction studies can be carried out intraoperatively and may be beneficial for assessing the physiological status of a section of traumatized nerve. Cortical mapping is valuable when surgical resections near motor or speech areas in the brain are contemplated and may help the surgeon avoid significant postoperative deficits in movement or language. Intraoperative stimulation for identifying spinal motor pathways may be used to guide surgical exploration. Finally, selective intraoperative stimulation for identifying nerve fibers encased in tumor may be useful for procedures involving difficult dissections along the brachial plexus or other major nerves in the arm or leg. PMID- 2197234 TI - Vanadium in chronic hemodialysis patients. PMID- 2197235 TI - Beta 2-microglobulin elimination characteristics during hemofiltration with acrylonitrile and polysulfone membrane hemofilters. AB - Elimination characteristics of beta 2-microglobulin (BMG) during hemofiltration (HF) with acrylonitrile (AN69) and polysulfone (PS) hemofilters were investigated in a prospective clinical investigation. Seven chronic uremics on regular HF were treated for 4 weeks, three times a week, with AN69 hemofilters. The study was then repeated with PS hemofilters. There were no significant differences in the patients' body weight, the ultrafiltrate volume per session, and the duration of each HF session between both treatments. At the start of HF, arterial plasma concentration of BMG was (for AN69) 33.5 +/- 4.0 mg/L (mean +/- SD) and (for PS) 35.8 +/- 6.5 mg/L (NS); at the end of HF it was (for AN69) 11.0 +/- 1.8 mg/L and (for PS) 17.5 +/- 4.2 mg/L (p less than 0.001). The amount of BMG in total ultrafiltrate was (for AN69) 179.3 +/- 22.6 mg and (for PS) 140.6 +/- 26.8 mg (p less than 0.02). With AN69 hemofilter, maximum BMG plasma clearance and sieving coefficient were 51.0 +/- 9.5 mL/min and 0.42 +/- 0.04 at 60 minutes. With PS hemofilter, maximum BMG plasma clearance and sieving coefficient were 37.4 +/- 5.7 mL/min and 0.27 +/- 0.03 at 15 minutes. Twenty-two percents of BMG entering the AN69 hemofilter at 15 minutes were adsorbed on the membrane (p less than 0.001). BMG elimination with the AN69 hemofilter was more efficient than with the PS hemofilter. Long-term studies will be necessary to demonstrate whether this difference is of any clinical significance. PMID- 2197236 TI - Hypothermia and respiratory care. PMID- 2197237 TI - [Indications for scintigraphy with gallium 67 and with indium 111 labelled leukocytes in the diagnosis of postoperative infections in osteo-articular surgery]. AB - A prospective scintigraphic study using Gallium 67 and granulocytes labelled with Indium 111 was carried out in 60 patients who were thought to have infection following orthopaedic operations. Both investigations gave positive results in 11 of the 16 infections observed. The Indium 111 labelled leucocyte scan was more accurate than the Gallium 67 studies in delineating patients who did not have an infection, and appears to be more reliable in the diagnosis of post-operative sepsis. PMID- 2197238 TI - Treatment of infected joint arthroplasty. AB - Sixty-two patients presented with an infected total hip arthroplasty. Their management depended on their general medical condition, the clinical signs of infection, the type of infection, the degree of fixation of the components and the available bone stock. Treatment consisted of one of the following: debridement and lavage without removing the prosthesis, one or two stage revision arthroplasty, or excision arthroplasty. There were 11 early and 51 late infections. The commonest bacterium isolated was Staphylococcus epidermidis (30%). Primary revision of the femoral component was slightly more successful with a cemented prosthesis than with an uncemented prosthesis. The overall success rates for cemented and uncemented femoral components were roughly comparable (91.5%:90%). We make various recommendations for the management of infected total hip arthroplasties based on our experience. PMID- 2197239 TI - Tumor markers of epithelial ovarian neoplasms. AB - Ninety-three formalin-fixed, paraffin-embedded surgical specimens from 69 ovarian tumors representing all five epithelial cell types were studied by immunohistochemistry, peanut and ulex lectin binding, and carbohydrate histochemistry. Carcinoembryonic antigen (CEA) was mostly noticeable in mucinous tumors (21 of 26). Glycogen was highly prevalent in clear cell (8 of 9) and endometrioid (4 of 6) carcinomas, in contrast to serous carcinomas (3 of 6), where it was only focally distributed, and was completely absent in all mucinous tumors. Among the different types of malignant tumors examined, mucinous carcinomas most frequently contained neutral mucins (6 of 8). In mucinous tumors, an increase in CEA content and a decrease in the total mucin secretion, particularly the strongly acidic sulfated group, were found to parallel the increased malignant potential of the tumor. Peanut and/or ulex lectin binding was a feature common to almost all epithelial neoplasms. Although peanut lectin showed a slightly higher affinity to serous and clear cell tumors, while ulex lectin was bound more to mucinous and endometrioid neoplasms, distribution of D galactose and L-fucose does not have a diagnostic utility in these tumors. Placental lactogen was detected in 3 of 17 benign tumors and one of 19 tumors of low malignant potential (LMP). The beta subunit of hCG was found in one of 17 benign tumors, in 2 of 19 LMP tumors, and in 3 of 31 carcinomas. PMID- 2197240 TI - Immunohistochemical characterization of a monoclonal antibody detecting an endometrioid ovarian cancer-associated antigen. AB - Murine monoclonal antibody FEN-1 was derived by immunizing Balb/c mice with an affinity-purified endometrioid ovarian cancer-associated antigen recovered from ascites-derived immune complexes. Splenic lymphocytes from the immunized mouse were fused with the myeloma cells SP2/0-AG14 in the presence of PEG 1500. The hybrid cultures were screened for production of immunoglobulins reactive with an extract preparation of an endometrioid ovarian tumor by enzyme-linked immunosorbent assay and flow cytometry. One of the hybrids secretes a monoclonal antibody of the IgG3 subtype designated FEN-1, which reacts with 100% of endometrioid ovarian cancer containing adenoacanthoma by indirect immunoperoxidase on paraffin-embedded tissue. No detectable levels of antigen were found in squamous metaplasia associated with nonendometrioid tumors, and no reactivity occurred against endometrial adenocarcinomas, endometriosis, or normal ovary and endometrium. The antibody does not cross-react with mucinous tumors, nonepithelial tumors of the ovary, or gastrointestinal tissue. This antibody may be used as an aid in the diagnosis of nonmucinous ovarian carcinomas by immunohistology. PMID- 2197241 TI - Epidermal growth factor receptor expression in the normal and inflamed cervix uteri: a comparison with estrogen receptor expression. AB - The expression of epidermal growth factor receptor (EGFR) was studied in the normal and inflamed cervix uteri, and the results were compared with estrogen receptor (ER) expression. The study was performed on fresh frozen specimens from 18 cases by means of immunohistochemistry, with application of EGFR1 antibody and an ER-ICA kit (Abbott, Wiesbaden, F.R.G.). The EGFR was expressed by the basal and parabasal layers of ectocervical and metaplastic epithelium and by reserve cells. No cyclic fluctuations in EGFR expression were noted. The glandular epithelium did not express EGFR. Some glands stained positive in the region of the basement membrane. Staining was not diminished in inflammatory foci, in contrast to ER expression, which was trace or absent. This was observed in both normal and dysplastic squamous epithelium. It may be assumed that the change of the normal relationship between ERs and EGFRs influences the process of proliferation and maturation of the squamous epithelium and may play a role in its disturbances. PMID- 2197242 TI - Malignant mixed mullerian tumor of the ovary with prominent neuroectodermal differentiation (teratoid carcinosarcoma). AB - We report a unique carcinosarcoma of the ovary having an organoid growth pattern that resembled immature teratoma. The tumor contained both adenocarcinoma and squamous carcinoma (focally sebaceous) admixed with chondrosarcoma, rhabdomyosarcoma, and malignant neuroectodermal components. The neuroectodermal components were prominent, resembling ependymoblastoma, medulloepithelioma, ganglioneuroblastoma, glioblastoma multiforme, and pigmented neuroectodermal tumor. Immunohistochemical studies dramatically revealed carcinoma and rhabdomyosarcoma admixed with malignant neuroectodermal tumor. Implants of papillary serous carcinoma (with psammoma bodies) were present in the opposite ovary, uterine serosa, omentum, and appendiceal serosa. Although a variant not previously described in the ovary, this ovarian carcinosarcoma closely resembled nasopharyngeal tumors described as teratoid carcinosarcoma or terato carcinosarcoma. PMID- 2197244 TI - Pseudocyesis--a review and report of six cases. AB - Pseudocyesis is a rare condition in which a woman believes herself to be pregnant when she is not. Its incidence has fallen in the last fifty years, probably due to a number of sociocultural and medical factors. Six cases are described which show common features of recent pregnancy loss or infertility, psychological and medical naivete, social isolation, recent loss and membership in a cultural or religious group that focuses on childbearing as the central role of women. Etiology includes psychological, sociocultural and endocrine factors which interact with each other demonstrating the reciprocal interplay between mind and body. Guidelines are provided for the assessment and management of this ancient and fascinating condition. PMID- 2197243 TI - Assessment of social relationships in elderly patients. AB - This article provides an overview of measures for assessing the importance of social relationships to the outcome of illness in the elderly. Review of the evidence associating social relationships with the variability in health outcome emphasizes the need for separating social relationships into three components: Social network structure and composition; Type and amount of social support provided through the network; and, perceived adequacy of the social support. Because of physical and social changes during the life cycle, care must be exercised in selecting and interpreting social relationship measures for use with the elderly. Available measures relevant for assessing the three components of social relationships in the elderly are described. PMID- 2197246 TI - Congenital aglossia and situs inversus. AB - Lingual agenesis is a rare anomaly caused by failed embryogenesis of the lateral lingual swellings during the fourth and fifth gestational weeks. Most reported cases have been part of oromandibular limb hypogenesis syndromes. A review of the literature reveals two previously reported cases of congenital aglossia and situs inversus. A case of lingual agenesis associated with micrognathia and situs inversus is reported in a newborn presenting with upper airway obstruction at birth. PMID- 2197245 TI - Abnormalities of the bony thorax causing tracheobronchial compression. AB - A number of intrathoracic and extrathoracic causes of airway obstruction have been well documented in the literature. At times, tracheal compression may be caused by abnormalities of the bony thorax whose previously unrecognized significance can result in unexpected difficulties when extubation is attempted following a routine intubation. Alternatively, patients may develop progressive distress secondary to their skeletal abnormalities. We report on cases illustrating anomalies of the manubrium, sternum and spine which have caused significant, occasionally life-threatening, tracheal and bronchial narrowing including pectus excavatum and scoliosis. A protocol is presented detailing the appropriate methods of diagnosis and treatment of these types of deformities. PMID- 2197247 TI - Orbital complications of sickle cell disease. AB - Swelling and pain of the peri-orbital tissues in patients with sickle cell disease has been described. This has most often been ascribed to orbital apex syndrome, but there are recent reports in the literature of frontal bone infarctions compounding this syndrome. We will present a case report of a child with sickle cell disease with bilateral orbital abscesses and frontal bone infarctions. The literature pertaining to the diagnosis and treatment of the orbital complications of sickle cell disease is reviewed. We stress that intravenous antibiotics are not adequate therapy for orbital abscesses and that these must be drained surgically. PMID- 2197248 TI - A European and global strategy for a nursing information network. AB - Information at every nurse researcher's fingertips. That is the goal of an information system for nursing services in Europe. Not only would it be able to provide fast information for analyzing and developing nursing but it also aspires to end the costly duplication of research work regionally and worldwide. Below, a report on how a European network can be developed to become a potential hub for a global nursing system. PMID- 2197249 TI - Comparative evaluation of an immunofluorescent antibody test, enzyme immunoassay and western blot for the detection of HIV-1 antibody. AB - Screening blood and blood products for human immunodeficiency virus type 1 (HIV 1) antibody is predominantly performed by enzyme immunoassay (EIA), and results must be confirmed by the more immunospecific Western blot (WB) assay. This study evaluated an HIV immunofluorescent antibody (IFA) test relative to WB assay for use in confirming EIA designated HIV-1 antibody-positive sera. Specimens from seroconversion and CDC panels as well as clinical specimens obtained for routine EIA HIV-1 antibody screening were evaluated. Results with 209 specimens indicated that sensitivity and specificity of the Fluorognost-HIV assay were equivalent relative to WB. In addition, the Fluorognost-HIV IFA test was faster and easier to perform than the WB assay, and unlike the WB assay was not prone to indeterminate results. PMID- 2197250 TI - [Cutaneous amyloidoses]. AB - Significant advances in basic research in biochemistry and immunology has tremendously increased our understanding of amyloidoses. The chemical structure of several amyloid proteins has been partly characterized. Specific antibodies may provide new methods for immunohistological diagnosis of amyloidoses. Cutaneous manifestations can affect the skin only or develop during the course of systemic amyloidoses. Although these conditions are so rare, dermatologists should be aware of the changing clinical manifestations of cutaneous amyloidoses if they wish to avoid diagnostic failures. PMID- 2197251 TI - [Integrins--new receptor molecules: their significance for the differentiation, regeneration and immune response of the skin]. AB - The integrins are a newly defined family of cell surface receptors. They are involved in the adhesion of cells to the extracellular matrix and to other cells. Integrins and their ligands may be required for complex physiological and pathophysiological events, such as epidermal differentiation, inflammation, immune response, wound healing or tumour progression. Some of the integrin receptor molecules are expressed in a distinct distribution pattern within the skin. Three of them are found selectively in the basal layer of the epidermis, suggesting an important role in establishment of the functional integrity of the dermo-epidermal junction. In the present paper we summarize the available data on the structure and function of integrins and report on the expression of these molecules within the skin and their regulation in cell cultures. PMID- 2197252 TI - [Halo eczema and nevus cell nevi (Meyerson nevi)]. AB - In the same way as a halo of depigmentation surrounds a sutton naevus, a halo of eczema can appear around a naevocellular naevus. This phenomenon was first described in 1971 by Meyerson, but publications on the topic are relatively sparse. We report a patient who consulted us because of such lesions. A review of literature is appended. PMID- 2197253 TI - [History of the Munich Dermatology Society]. PMID- 2197254 TI - [Soft tissue infection--osteitis--osteomyelitis]. AB - Statistically the posttraumatic osteitis shows a clear tendency to decrease from 1972-76 in comparison with 1982-86 (AO/ASIF-documentation). The incidence of infection varies considerably according to the different anatomical location of fractures. More recently atypical manifestations became of more importance and ask for differentiated bacteriological examinations. A close postoperative follow up and exact wound-observations enable an immediate and adequate therapy in case of an infection. PMID- 2197255 TI - [Post-traumatic osteitis. The acute infection]. AB - The acute infection is defined as bacterial growth within the surgical wound, that may occur within days to weeks after initial surgery but before bone union. The chances of complete recovery after an acute soft tissue inflammation are closely related to the interval between initial surgery and first signs of infection, the early recognition of the complication, the type of bacteria involved and the therapeutic measures. The first symptoms of an impending infection are the classical clinical ones of any inflammation: tenderness, swelling and reddening. All imaging procedures are of little or no value. The therapy consists of very aggressive and, if required, repeated wound revisions with debridement of all necrotic tissue, removal of loose bone fragments or loose implant material, wash-outs with antiseptic solutions (e.g. Taurolin) or even deposition of gentamycin beads. Systemic antibiotics may be added temporarily. The in- or external fixation devices must provide stable fracture fixation and the bone as well as the soft tissue envelope must be well vascularized. PMID- 2197256 TI - [Value of hyperbaric oxygen therapy in the treatment of post-traumatic osteitis]. PMID- 2197257 TI - [Value of systemic and local administration of antibiotics in soft tissue and bone infections]. AB - There is little data to support the efficacy of prophylactic antibiotics in traumatology. In closed fractures three randomized controlled studies using a 1-3 day prophylaxis with Cephalosporins of the first or second generation or a Penicillinase-resistent Penicillin demonstrated a reduction of the infection rate. For the Cephalosporins of the second generation it was shown, that a single dose was less efficient than five repeated applications over 24 hours. In hip fractures a prophylaxis with Cephalothin or Cefotiam reduced the frequency of infections when compared with controls. In open fractures a treatment over 10 days using Cephalothin or Isoxazolyl-Penicillin showed a significant drop of the infection rate. If however the fractures were not treated using the principles of rigid internal fixation and were covered with Dicloxacillin over 2 days only there was no significant improvement. A multicenter study finally indicates that a one day course of cefonicid sodium is not inferior to a prolonged course of antibiotics for prevention of early postoperative fracture-site infections. We conclude, that open and closed fractures can profit from antibiotic prophylaxis which starts immediately before surgery and is continued over 24 hours. We favour Isoxazolyl-Penicillin because of its efficacy against staphylococcus aureus and epidermidis which predominate in early infection. In established bone and soft tissue infections antibiotics are used when there is local spreading, sepsis, involvement of joints or when reinterventions in the infectious focus are necessary. In these cases bacteriological testing in the laboratory is essential for the selection of antibiotics. Local application of antibiotics in irrigation drainage solutions can not be recommended. PMMA-chains serve as temporary spacers, but should be removed early before their extraction becomes difficult and resistant bacteria develop. When defects are closed with cancellous bone or soft tissues the use of Gentamycin-fleece or Taurolin-gels is recommended. PMID- 2197258 TI - [Intraoperative sonography]. AB - Intraoperative sonography was introduced at our institution in November 1987. We have since examined 55 patients, of which 27 suffered from liver disease, 16 from pancreatic problems and 11 from hyperparathyroidism. A short description of the technique applied is given for each organ. The intraoperative sonography of the liver showed additional information in one third of the cases. The sensitivity of intraoperative sonography in hyperparathyroidism was 78%, the specificity 72%. PMID- 2197259 TI - [Single-layer suture to re-establish the digestive continuity following partial gastrectomy]. AB - We have introduced progressively since 1985 the single-layer continuous suture technique for gastroenteric anastomoses, since this technique has been proved to be safe in colonic anastomosis. From 117 gastrectomies performed between 1985 and 1988, 68 gastroenteric anastomoses were performed with the single-layer continuous suture technique (58%). In 1988 this technique has been applied to 92.5% of the gastroenteric anastomoses. The complication rate is low: 3% clinical leakage were found. We concluded that the single-layer continuous suture technique for gastroenteric anastomoses is safe, very simple and easy to perform. It is the logical extension to large and small bowel anastomoses that we have been doing, using this technique for over 4 years now with excellent results. PMID- 2197260 TI - [Status of the Delorme operation in surgery of rectal prolapse]. AB - The surgical treatment of complete rectal prolapse has been the object of great controversy. Currently, it is believed that best results are obtained by transabdominal rectopexy. Even though these operations have low morbidity and mortality, a laparotomy may not be advisable for certain elderly or poor-risk patients. An alternative would then be the Delorme operation. The principle consists of an extensive perineal excision of the mucosa covering the prolapse, and a longitudinal plication of the rectal wall. From January 1988 to March 1989, 12 patients underwent the Delorme repair of rectal prolapse in our service with good results. PMID- 2197261 TI - Treatment of pelvic inflammatory disease and related matters. PMID- 2197262 TI - Use of a non-radioactive DNA hybridization technique to study the effect of quinolone antibiotics on plasmid replication and curing. AB - A biotin-labelled DNA probe was used to detect the presence of bacteria carrying plasmid DNA and to study the effect of ciprofloxacin and nalidixic acid on plasmid carriage. The colour intensity generated in dot-blot hybridization tests was measured with a computer-controlled image analysis system and was shown to be related to the number of plasmid copies present. Ciprofloxacin, at about 0.5 x MIC, reduced the plasmid copy number in a bacterial population, while nalidixic acid, used at a similar ratio to MIC, had a much smaller effect. The method could potentially be used to study the effect of antibiotics on plasmid replication and curing in any bacterial system for which a suitable DNA probe is available. PMID- 2197263 TI - Beta-lactam antibiotics (aztreonam, ampicillin, cefazolin and ceftazidime) in the control and eradication of Salmonella typhimurium in naturally resistant and susceptible mice. AB - This study was undertaken to investigate the efficacy of different beta-lactam antibiotics in the treatment of systemic salmonella infections in the mouse typhoid model. Innately susceptible BALB/c (Itys) and resistant CBA (Ityr) mice were used to investigate the efficacy of one monocyclic (aztreonam) and three bicyclic (ampicillin, cefazolin, ceftazidime) beta-lactam antibiotics in controlling systemic salmonella infections when given for brief or prolonged periods. The present study confirms and amplifies earlier reports on ampicillin therapy, demonstrates marked differences in the efficacy of the different antibiotics and shows that aztreonam is not only very effective but can completely eradicate the salmonellae from the RES when given early in the infection. PMID- 2197264 TI - Intraperitoneal ciprofloxacin for the treatment of peritonitis in patients receiving continuous ambulatory peritoneal dialysis (CAPD). AB - Ciprofloxacin was evaluated as single-agent therapy for the empirical treatment of patients presenting with CAPD peritonitis in an open, uncontrolled trial. Seventy-five episodes of peritonitis in 44 patients receiving continuous ambulatory peritoneal dialysis were entered in the study. The antibiotic was administered intraperitoneally, at a dose of 50 mg/l in each bag of dialysate, for seven days. Treatment with ciprofloxacin was appropriate (organisms isolated sensitive to ciprofloxacin) and successful (clinical and bacteriological cure of peritonitis) in 62 (83%) of the 75 episodes. The mean ciprofloxacin concentrations in serum and effluent were 1.1 mg/l (range 0-2.9 mg/l) and 10.0 mg/l (range 0.2-33.4 mg/l), respectively, with no evidence of accumulation. Side effects were seen in two patients only, and were mild and transitory. PMID- 2197265 TI - Chronic myelogenous leukemia with typical clinical and morphological features can be Philadelphia chromosome negative and "bcr negative". AB - The Philadelphia (Ph1) chromosome is found in the majority of patients affected by chronic myelogenous leukemia (CML), being considered the hallmark of the disease, but around 5-8% of patients diagnosed as CML lack the Ph1 chromosome negative (Ph-) CML has been discussed extensively in the literature because of its heterogeneity. However, it is now accepted that some of the Ph1-CML patients have a disease indistinguishable from Ph1-positive (Ph+) CML. It was investigated whether Ph- CML with clinical and morphological features indicating true CML would always have bcr rearrangements, as the relocation of c-abl from 9q34 into the breakpoint cluster region on 22q11 is considered a crucial event in the pathogenesis of CML. From molecular studies, it seemed that Ph- CML with features of true CML always have the bcr rearrangement, while Ph- patients, lacking such rearrangement, have atypical forms of CML. Here we describe 8 Ph- CML and myeloproliferative syndrome (MPS) patients of whom 6 were by all respects true CML cases. Nevertheless, bcr rearrangement and expression of the classic bcr/abl chimeric mRNA was found in only 1 of the 6 patients. More advanced molecular techniques will be needed to understand which molecular mechanisms underlie Ph-, bcr- CML, resulting in phenotypes sometimes indistinguishable from Ph+, bcr+ CML. PMID- 2197266 TI - Bone marrow changes in patients with refractory aplastic anemia treated by recombinant GM-CSF. AB - The morphologic changes in the bone marrow of eight patients with refractory aplastic anemia who received 4 or more weeks of granulocyte macrophage-colony stimulating factor (GM-CSF) are described. All eight patients demonstrated a continuous rise in the absolute number of neutrophils, eosinophils, and monocytes over the first four weeks of therapy. Bone marrow examination revealed a progressive increase in bone marrow cellularity in all patients except one. An increase in myeloid: erythroid ratio was seen with progressive maturation of granulocytic cells. Neutrophilic and eosinophilic myelocytes were the most prominent cells. The percentage of myeloblasts and promyelocytes did not increase significantly, and the proportions of postmitotic granulocytic cells did not change either. No significant morphologic changes were noted in the basophilic, erythroid, and megakaryocytic series. The most prominent topographic observation in the bone marrow during GM-CSF therapy was the frequent clustering of myeloid cells close to the bone trabeculae. The periosteal localization of myeloid precursors may reflect a higher concentration of stem cells and/or stromal cells in the bone marrow adjacent to the bone trabeculae or a higher concentration of growth factors. Careful morphologic examination of bone marrow in CSF clinical trials will provide useful information regarding the in vivo effects of these growth factors, and will aid in the development of a rational approach to combining them for therapy. PMID- 2197267 TI - Differential effect of continuous versus cyclic maintenance chemotherapy on cytokine-induced myeloid colony growth. AB - Myeloid colony growth by bone marrow cells obtained from pediatric cancer patients was stimulated by granulocyte-macrophage colony-stimulating factor (GM CSF) and/or interleukin 1 (IL-1). Although patients recovering from cyclic high dose chemotherapy showed normal colony growth in response to GM-CSF, patients with acute lymphoblastic leukemia (ALL) receiving continuous maintenance chemotherapy at moderate dose had variable but often severe decreases in myeloid colony growth compared with controls. Marrow from all patients and controls demonstrated enhanced colony growth in GM-CSF-stimulated cultures which also contained IL-1. For patients on continuous daily maintenance therapy for ALL, enhancement of myeloid colony growth in response to IL-1 was proportional to the decrease in colony growth in response to GM-CSF. These observations support a possible clinical role for GM-CSF or other direct stimulators of myeloid growth in the patients receiving episodic high doses of chemotherapy, but suggest that alternative strategies may be more effective for those patients receiving chronic moderate-dose chemotherapy. PMID- 2197268 TI - The Edgerton time microscope. PMID- 2197269 TI - Heat shock proteins. PMID- 2197270 TI - Insulin activates the kinase activity of the Raf-1 proto-oncogene by increasing its serine phosphorylation. AB - Insulin was found to stimulate the serine/threonine kinase activity of the proto oncogene product Raf-1. This stimulation was observed in HeLa, NIH 3T3, and Chinese hamster ovary cells, all overexpressing the human insulin receptor. In the HeLa cells, 100 pM insulin gave a significant increase in Raf-1 kinase activity, and 100 nM insulin caused a maximal 2-5-fold increase in activity. The increase in activity was detected after 2 min of insulin treatment and peaked after 5 min. In addition to stimulating Raf-1 kinase activity, insulin caused a shift in the electrophoretic mobility of the Raf-1 protein and an increase in the amount of serine phosphorylation of Raf-1. Moreover, a serine/threonine-specific phosphatase, phosphatase 1, but not two tyrosine-specific phosphatases, was found to deactivate the insulin-activated Raf-1 kinase activity. These findings indicate that insulin activates the serine/threonine kinase activity of the Raf-1 proto-oncogene by increasing its content of phosphoserine. PMID- 2197271 TI - Insulin activates the Raf-1 protein kinase. AB - Several growth factors and mitogens have been shown to activate the proto oncogene product Raf-1 protein kinase in murine fibroblasts, apparently through a direct agonist-stimulated tyrosine phosphorylation of the Raf-1 protein. We investigated the possibility that insulin could also activate the Raf-1 kinase, since its receptor also contains an intrinsic insulin-activated protein tyrosine kinase activity. In several cell lines expressing relatively large numbers of insulin receptors, insulin rapidly stimulated the phosphorylation of immunoreactive Raf-1 protein. In H35 cells, a line of well differentiated rat hepatoma cells, the effect of insulin was maximal by 6 min and at 7 nM insulin and occurred normally in cells virtually completely depleted of protein kinase C activity. The insulin-stimulated increase in Raf-1 protein phosphorylation occurred concurrently with a 3-fold increase in Raf-1 protein kinase activity. However, phosphoamino acid analysis showed that only phosphoserine and a trace of phosphothreonine were present in the Raf-1 protein after insulin stimulation of the cells. This was true even when investigated at shorter times (4 min) after insulin stimulation and despite the use of phosphotyrosine phosphatase inhibitors. We conclude that insulin can rapidly activate the Raf-1 kinase in some insulin-sensitive cell types but that this activation probably occurs through a mechanism distinct from direct phosphorylation of the Raf-1 protein by the insulin receptor protein tyrosine kinase. PMID- 2197272 TI - UhpT, the sugar phosphate antiporter of Escherichia coli, functions as a monomer. AB - We have characterized the minimal functioning unit of UhpT, the secondary carrier that mediates exchange of phosphate and glucose 6-phosphate in Escherichia coli. Membranes of a UhpT overproducing strain were solubilized with 1.25% octyl beta-D glucopyranoside, in the presence of 0.1% E. coli phospholipid and with 20% glycerol as the osmolyte stabilant. That soluble UhpT could bind its natural substrates was indicated by the protections afforded by sugar phosphates against thermal inactivation or chemical modification with pyridoxal 5'-phosphate. Moreover, the degree of protection correlated with the strength of interaction between UhpT and the test substrate (2-deoxyglucose 6-phosphate = glucose 6 phosphate greater than galactose 6-phosphate = glucose 1-phosphate much greater than glucose 6-sulfate). Other experiments demonstrated that soluble UhpT existed as a monomer. For example, during both high performance liquid chromatography and conventional gel permeation chromatography, the elution pattern of UhpT activity was measured directly by a rapid reconstitution technique. In both cases, and in the presence and absence of substrate, UhpT activity traveled as a single component of Mr 53,000, corresponding closely to the sequence prediction of 50,600. Finally, reconstitution was studied at protein to lipid ratios low enough to achieve between 0.075 and 1.5 UhpT monomers/proteoliposome. Specific activity was constant throughout this range, a finding consistent with the idea of a functional monomer. Mitochondria and chloroplasts provide the only other anion exchange carriers described at this level of biochemical resolution, and these organelle antiporters function as dimers. By contrast, work summarized here places their bacterial counterpart, UhpT, in the same class as the lactose carrier of E. coli and the glucose carrier of the human erythrocyte, both of which function as monomers. Consideration of this pattern in conjunction with the known hydropathy profiles of these proteins suggests a novel scheme for the classification of all secondary carriers, with implications for both the structure and origin of these transport proteins. PMID- 2197273 TI - Cloning metabolic pathway genes by complementation in Escherichia coli. Isolation and expression of Plasmodium falciparum glucose phosphate isomerase. AB - Genetic complementation of an Escherichia coli double mutant was used to isolate and express the gene coding for Plasmodium falciparum glucose phosphate isomerase. The gene contains a 1773-base pair open reading frame, has no introns, and maps to P. falciparum chromosome 14. 34% of the deduced amino acid sequence is identical to human glucose phosphate isomerase, with highest similarity in regions of the proposed active sites. The putative initiation site of translation was determined by deletional and oligonucleotide mediated, site-specific mutageneses. Our data suggest that key metabolic enzymes of Plasmodia can be cloned and expressed in E. coli without prior knowledge of the primary amino acid or nucleic acid structure. PMID- 2197274 TI - Cloning, sequencing, and expression of the genes encoding the adenosylcobalamin dependent ethanolamine ammonia-lyase of Salmonella typhimurium. AB - Ethanolamine ammonia-lyase is a bacterial enzyme that catalyzes the adenosylcobalamin-dependent conversion of certain vicinal amino alcohols to oxo compounds and ammonia. Studies of ethanolamine ammonia-lyase from Clostridium sp. and Escherichia coli have suggested that the enzyme is a heterodimer composed of subunits of Mr approximately 55,000 and 35,000. Using a partial Sau3A Salmonella typhimurium library ligated into pBR328 and selecting by complementation of a mutant lacking ethanolamine ammonia-lyase activity, we have cloned the genes for the 2 subunits of the S. typhimurium enzyme. The genes were localized to a 6.5 kilobase fragment of S. typhimurium DNA, from which they could be expressed in E. coli under noninducing conditions. Sequencing of a 2526-base pair portion of this 6.5-kilobase DNA fragment revealed two open reading frames separated by 21 base pairs. The open reading frames encoded proteins of 452 and 286 residues whose derived N-terminal sequences were identical to the N-terminal sequences of the 2 subunits of the E. coli ethanolamine ammonia-lyase, except that residue 16 of the large subunit was asparagine in the E. coli sequence and aspartic acid in the S. typhimurium sequence. PMID- 2197275 TI - Sequence and structure of Clp P, the proteolytic component of the ATP-dependent Clp protease of Escherichia coli. AB - The ATP-dependent Clp protease of Escherichia coli contains two dissimilar components: the Clp A regulatory polypeptide, with two ATP binding sites and intrinsic ATPase activity, and the Clp P subunit, which contains the proteolytic active site. The DNA sequence of the clpP gene predicts a protein of 207 amino acids (Mr 21,679), which is in close agreement with the size determined by sodium dodecyl sulfate-gel electrophoresis of purified Clp P. Clp P has a native Mr of approximately 240,000, and electron micrographs of the protein show superimposed disk-like structures with a central cavity, similar in appearance to purified proteasomes from eukaryotic cells. Clp P is synthesized with a 14-amino acid leader which is rapidly cleaved in vivo to yield the 193-amino acid protein which has activity in vitro. The clpP gene is at 10 min on the E. coli map, close to that for the ATP-dependent Lon protease of E. coli and far from the gene for clpA. Primer extension experiments indicate that transcription initiates immediately upstream of the coding region for Clp P, with a major transcription start at 120 bases in front of the start of translation. Insertion mutations in clpP have been isolated and transferred to the chromosome; strains devoid of Clp P are viable in the presence or absence of Lon protease. Mutations in clpP stabilize the same Clp A-beta-galactosidase fusion protein specifically stabilized by clpA mutations, providing the first genetic evidence that Clp A and Clp P act together in vivo. PMID- 2197276 TI - Clp P represents a unique family of serine proteases. AB - The amino acid sequence of Clp P, the proteolytic subunit of the ATP-dependent Clp protease of Escherichia coli, closely resembles a protein encoded by chloroplast DNA, which is well conserved between chloroplasts of different plant species. The homology extends over almost the full length of the sequences of both proteins and consists of approximately 46% identical and approximately 70% similar amino acids. Antibodies against E. coli Clp P cross-reacted with proteins with Mr of 20,000-30,000 in bacteria, lower eukaryotes, plants, and animal cells. Since the regulatory subunit of Clp protease, Clp A, also has a homolog in plants, as well as in other bacteria and in lower eukaryotes, it is likely that ATP-dependent proteolysis in chloroplasts is catalyzed in part by a Clp-like protease and that both components of Clp-like proteases are widespread in living cells. We have identified Ser-111 as the active site serine in E. coli Clp P modified by diisopropyl fluorophosphate. Mutational alteration of Ser-111 or His 136 eliminates proteolytic activity of Clp P. Both residues are found in highly conserved regions of the protein. The sequences around the active site residues suggest that Clp P represents a unique class of serine protease. Amino-terminal processing of cloned Clp P mutated at either Ser-111 or His-136 occurs efficiently when wild-type clpP is present in the chromosome but is blocked in clpP- hosts. Processing of Clp P appears, therefore, to involve an intermolecular autocatalytic cleavage reaction. Since processing of Clp P occurs in clpA- cells, the autoprocessing activity of Clp P is independent of Clp A. PMID- 2197277 TI - A biological role of the carbohydrate moieties of laminin. AB - The ways in which the carbohydrate moieties of laminin affect its cellular interactions have been examined by two different experimental approaches. In one approach, we used lectins in order to block specific carbohydrates on laminin which previously had been dried onto a plastic surface. We found that wheat germ agglutinin and Griffonia simplicifolia agglutinin I blocked the binding of the neuron-like rat pheochromocytoma cell line PC12. However, when concanavalin A was used cell binding was unaffected but neurite outgrowth was prevented, compared to controls, over a 24-h period. In the second approach we used unglycosylated laminin as a substratum on the plastic surface. We have developed a method for the purification of unglycosylated laminin from tunicamycin treated cultures of a mouse embryonal carcinoma derived cell line, M1536 B3, and have partially characterized the purified material. A mixture of unglycosylated and glycosylated laminin was selectively purified from the M1536 B3 cell lysate by an anti-EHS laminin monoclonal antibody immunoaffinity column. The unglycosylated laminin was separated from glycosylated laminin using G. simplicifolia lectin affinity chromatography. The lectins, wheat germ agglutinin, G. simplicifolia agglutinin I, and concanavalin A, did not bind to any of the subunits of unglycosylated laminin in Western blots. The unglycosylated laminin migrated as a single band in agarose-gel electrophoresis under nonreducing conditions indicating that it is a fully assembled and disulfide bonded molecule. Circular dichroism studies showed no differences between glycosylated and unglycosylated laminin, indicating similar molecular conformations. Western blots using antibodies specific for the A, B1, and B2 chains of laminin showed that unglycosylated laminin contained each of these subunits. We then performed cell binding and spreading or neurite outgrowth assays using unglycosylated laminin. A mouse melanoma cell line, B16 F1, bound to this laminin in the same numbers as to the control glycosylated laminin, but cell spreading was minimal. When this unglycosylated laminin was used as a substrate for PC12 cells neurite outgrowth was impaired; no effect was noted on the number of cells bound, compared to glycosylated laminin. We conclude from these results that once cells become bound to laminin the carbohydrate residues of that glycoprotein must be available to enable the cells to spread or to extend neurite processes. PMID- 2197278 TI - Light-dependent D1 protein synthesis and translocation is regulated by reaction center II. Reaction center II serves as an acceptor for the D1 precursor. AB - Light induces an irreversible modification of the photosystem II reaction center (RCII) affecting specifically one of its major components, the D1 protein (Ohad, I., Adir, N., Koike, H., Kyle, D. J., and Inoue, Y. I. (1990) J. Biol. Chem. 265, 1972-1979) which is degraded and replaced continuously (turnover). The turnover rate of D1 is related to light intensity. Evidence is presented showing that RCII translocates from the site of damage in the grana (appressed) domain of the chloroplast membranes to unappressed membrane domains where the D1 precursor protein (pD1) is translated and becomes integrated into RCII. Several forms of RCII (a, a*, and b) were identified on the basis of their electrophoretic mobility. pD1 was found only in the a and b forms in the unappressed membranes. Processing of pD1 occurs after its integration into RCII. Mature D1 appeared mostly in the a form of RCII and following its translocation to the appressed membrane domains also in the a* form. Thus the light intensity-dependent synthesis of D1 protein is related to the availability of modified RCII which serves as an acceptor for pD1. The shuttling of RCII between the two membrane domains may represent a control mechanism of thylakoid membrane protein synthesis. PMID- 2197279 TI - Mammalian DNA ligases. Biosynthesis and intracellular localization of DNA ligase I. AB - Mammalian DNA ligase I is presumed to act in DNA replication. Rabbit antibodies against the homogeneous enzyme from calf thymus inhibited DNA ligase I activity and consistently recognized a single polypeptide of 125 kDa when cells from an established bovine kidney cell line (MDBK) were lysed rapidly by a variety of procedures and subjected to immunoblotting analysis. After biosynthetic labeling of MDBK cells with [35S]methionine, immunoprecipitation experiments revealed a polypeptide of 125 kDa that did not appear when purified calf thymus DNA ligase I was used in competition. A 125-kDa polypeptide was adenylated when immunoprecipitated protein from MDBK cells was incubated with [alpha-32P]ATP. Thus, the apparent molecular mass of the initial translation product is identical or nearly so to that of the purified enzyme. The half-life of the protein is 7 h as determined by pulse-chase experiments in asynchronous MDBK cells. Immunocytochemistry and indirect immunofluorescence experiments showed that DNA ligase I is localized to cell nuclei. PMID- 2197280 TI - Protein composition of Vitreoscilla hemoglobin inclusion bodies produced in Escherichia coli. AB - The protein composition of inclusion bodies produced in recombinant Escherichia coli overproducing Vitreoscilla hemoglobin (VHb) was analyzed by one-dimensional and two-dimensional electrophoresis techniques. Results indicate the presence of two types of cytoplasmic aggregates of differing morphology in single bacterial cells. These aggregates also differ in their relative content of VHb and pre-beta lactamase and are separable by differential centrifugation. Results further suggest that the cytoplasmic protein elongation factor Tu is integrated into VHb inclusion bodies. The presence of the outer membrane proteins OmpA and OmpF in inclusion body preparations is attributed to cell envelope contamination rather than specific involvement in inclusion bodies. The specificity of in vivo protein aggregation is discussed. PMID- 2197281 TI - A numerical analysis of steady flow in a three-dimensional model of the carotid artery bifurcation. AB - A finite element approximation of steady flow in a rigid three-dimensional model of the carotid artery bifurcation is presented. A Reynolds number of 640 and a flow division ratio of about 50/50, simulating systolic flow, was used. To limit the CPU- and I/O-times needed for solving the systems of equations, a mesh generator was developed, which gives full control over the number of elements into which the bifurcation is divided. A mini-supercomputer, based on parallel and vector processing techniques, was used to solve the system of equations. The numerical results of axial and secondary flow compare favorably with those obtained from previously performed laser-Doppler velocity measurements. Also, the influence of the Reynolds number, the flow division ratio, and the bifurcation angle on axial and secondary flow in the carotid sinus were studied in the three dimensional model. The influence of the interventions is limited to a relatively small variation in the region with reversed axial flow, more or less pronounced C shaped axial velocity contours, and increasing or decreasing axial velocity maxima. PMID- 2197282 TI - Bilateral femoral neck fractures after electrical injury: a case report and literature review. AB - Simultaneous bilateral fractures of the femoral necks are rare injuries, especially when there is no underlying pathologic condition. A review of the literature revealed only 10 cases of this injury as a result of trauma, only one of which was due to accidental electric shock. A second case in which such an injury was caused by accidental electric shock is presented here. It is important to be aware of this injury and to diagnose it early to avoid the increased risk of complications after a delay in diagnosis or treatment. PMID- 2197283 TI - Cardiovascular rehabilitation of patients with burns. PMID- 2197284 TI - Vitamin supplementation in the patient with burns. PMID- 2197285 TI - A filamentous network surrounding secretory granules from mast cells. AB - A freezing-thawing method for rupturing mast cells has made it possible to show that each of the secretory granules is surrounded by a regular network of filaments forming a basket-like structure. The filaments attach to the membrane with hook-like structures. Immunoelectron microscopy of intact mast cells shows that actin occurs mainly in the subplasmalemmal space, whereas in ruptured cells it is seen around granules, indicating that the granule network might consist of actin. PMID- 2197286 TI - Pulsed field gel electrophoresis and investigations into mammalian genome organization. PMID- 2197287 TI - Distribution of tubulin and actin through the cell division cycle of the fission yeast Schizosaccharomyces japonicus var. versatilis: a comparison with Schizosaccharomyces pombe. AB - Changes in the distribution of microtubules and F-actin through the cell division cycle of the fission yeast Schizosaccharomyces japonicus var. versatilis were investigated by fluorescence microscopy. The fluorescence images obtained with S. japonicus were markedly superior to those previously reported for S. pombe and revealed new details of cytoskeletal organization in this important genus. As in S. pombe, F-actin in S. japonicus was present as a concentration of 'dots' at the growing poles of interphase cells and as a filamentous equatorial ring directing the deposition of the cytokinetic septum. The transition between these two states occurred at late anaphase, in contrast to the situation in S. pombe where the appearance of the equatorial actin ring is tightly coupled to the early events of mitosis. During the course of cytokinesis in S. japonicus the actin ring constricted and broadened, suggesting that it is contractile. Microtubule organization in S. japonicus also revealed interesting differences from S. pombe. Whereas in S. pombe cytoplasmic microtubules are reinitiated from a pair of microtubule organizing centres (MTOCs) at the cell equator, in S. japonicus they arise by extensive microtubule growth from the spindle poles. Western blots of cell extracts enriched for tubulin by DEAE-Sephadex chromatography showed that, like S. pombe, S. japonicus contains two alpha-tubulins and a single beta tubulin. Whilst the alpha 1- and beta-tubulins from the two species comigrated on one-dimensional polyacrylamide gels, the alpha 2 species were electrophoretically distinct. Although fundamental differences clearly exist between the two species, S. japonicus could prove to be a useful tool in basic studies of fission yeast cell biology. PMID- 2197288 TI - Stability of microtubule attachment to metaphase kinetochores in PtK1 cells. AB - Kinetochore microtubules are known to be differentially stable to a variety of microtubule depolymerization agents compared to the non-kinetochore polar microtubules, but the dynamics of microtubule attachment to the kinetochore is currently controversial. We have examined the stability of kinetochore microtubules in metaphase PtK1 spindles at 23 degrees C when microtubule assembly is abruptly blocked with the drug nocodazole. Metaphase cells were incubated in medium containing 34 microM nocodazole for various times before fixation and processing either for immunofluorescence light microscopy or serial-section electron microscopy. Microtubules not associated with kinetochore fibers disappeared completely in less than 1 min. Kinetochore fibers persisted and shortened, as the spindle poles moved close to the chromosomes over a 10-20 min interval. During this shortening process, the number of kinetochore microtubules decreased slowly. The mean number of kinetochore microtubules was 24 +/- 5 in control cells and zero in cells incubated with nocodazole for 20 min. The half time of microtubule attachment to the kinetochore was approximately 7.5 min. These results show that when microtubule assembly is blocked, kinetochore microtubules shorten more slowly and persist about 10 times longer than the labile polar microtubules. If kinetochore microtubules shorten by tubulin dissociation at their plus-ends like the non-kinetochore polar microtubules, then the microtubule surface lattice must be able to translocate through the kinetochore attachment site without frequent detachment occurring. PMID- 2197289 TI - Identification and protein kinase C-dependent phosphorylation of alpha-adducin in human fibroblasts. AB - A protein of Mr approximately 120,000, related to the human erythrocyte membrane skeletal protein alpha-adducin, has been identified by immunological criteria in human fibroblasts. Using similar methods, beta-adducin (an Mr approximately 110,000 protein that forms a dimeric complex with alpha-adducin in the erythrocyte) is not present in fibroblasts. Subcellular distribution studies reveal that fibroblast alpha-adducin is largely associated with the particulate fraction and is most effectively solubilized from that fraction by a combination of nonionic detergent and high salt. Immunocytochemistry of quiescent fibroblasts shows that alpha-adducin is clustered in large perinuclear arrays that may correspond to vesicular structures; weak staining was also found in the sub plasma membrane region. As in erythrocytes, the phosphorylation of fibroblast alpha-adducin is elevated on exposure of cells to phorbol esters that activate protein kinase C (PK-C). In addition, various mitogens such as serum, bradykinin and vasopressin also stimulate alpha-adducin phosphorylation by a PK-C-dependent pathway. The elevation in alpha-adducin phosphorylation is maintained for up to 30 min after mitogen addition. Peptide maps of phospho-alpha-adducin from both fibroblasts and erythrocytes after PK-C-mediated phosphorylation showed multiple phosphorylated peptides but with dissimilar migration patterns, suggesting divergence of structure around the phosphorylation sites. Adducin appears to play an important role in the regulation of spectrin-actin interactions in the red cell and may play a role in cytoskeletal function in the fibroblasts. PMID- 2197290 TI - [Duodenal leiomyoblastoma. Apropos of a new case and review of the literature]. AB - The authors report a new case of duodenal leiomyoblastoma. Since local anatomical factors were favorable, the tumor was removed by resecting the entire second portion of duodenum with reanastomosis of the remaining ends. This case can be added to the very small number of cases reported in the literature regarding leiomyoblastoma at this site in the gastrointestinal tract. Since diagnostic is difficult, and often made per-operatively following and acute complication, a precise topographical study of the region needs to be performed. It is only by this means that a completely safe operative procedure may be chosen and performed. From an anatomo-pathological viewpoint, several criteria exist to distinguish the potentially benign from the potentially malignant form. However, this remains to be confirmed given the controversial aspects of the subject. Study has mainly involved gastric localisations where a greater number of lesions have been found. At present, only time will show whether these tumors are benign or malignant. PMID- 2197291 TI - [Angiomyolipoma and polycystic kidney secondary to Bourneville's tuberous sclerosis]. AB - We describe the case of a previously healthy young woman admitted to hospital for abdominal pain and symptoms of shock. The preoperative diagnosis arrived at was polycystic kidney disease associated with ruptured angiomyolipoma. This combined pathology is pathognomonic of tuberous sclerosis; skin signs of the disease were also present in the patient, although undetected till then. The lack of neurological symptoms was an extraordinary finding. Cure is achieved at the cost of nephrectomy. PMID- 2197292 TI - [Carcinoid liver tumors. Apropos of a case]. AB - The authors report here a case of a young 35 years-woman presenting a probably primitive liver carcinoid tumor, surgically managed by hepatectomy followed by a complete disappearance of the carcinoidal syndrome. Through this case, the authors discuss the diagnostic difficulties, actuality of primitive hepatic carcinoids, their course, prognosis elements and the therapeutical management means. PMID- 2197293 TI - [Lipoma of the stomach. Apropos of a case. Review of the literature]. PMID- 2197294 TI - In memoriam. L. Stefan Levin. 1939-1989. PMID- 2197296 TI - A computerized approach to cognitive behavioural assessment: an introduction to CBA-2.0 primary scales. AB - The Cognitive Behavioural Assessment-2.0 (CBA-2.0) Primary Scales is an automated assessment package investigating the cognitive-verbal response system. It consists of: (1) self-reports and questionnaires aimed at identifying and specifying patients' problems; (2) a group of programs and logical rules, implemented on personal computers, providing an editor with items, questionnaire scoring and an analysis of responses; (3) an intelligent program which analyzes the responses emerging from the questionnaires and forms hypotheses for the selection of Secondary Scales and for further assessment. The package is part of a research project aimed at reducing part of the decision-making process to an operational language and simulating behavioral therapists decisions in cases of clinical assessment. PMID- 2197295 TI - A morphometric analysis of the fetal craniofacies by ultrasound: fetal cephalometry. AB - We present here a set of 24 standardized linear measurements that describe the growth of different craniofacial structures in the normal fetus from 16 to 36 weeks of gestation. These measurements were taken from 89 pregnant women, who had from 1 to 3 ultrasonographic evaluations during the pregnancy (16, 26, and 36 weeks of gestation). All the values presented here were obtained using the technique described by Escobar et al. The mean and standard deviation was calculated for each measurement and was used to estimate the normal growth pattern of each variable. Approximate confidence intervals for the mean of each variable were constructed for use in identifying unusually low or high values. The confidence intervals are available in graphic form by request. These data will not only contribute to an understanding of fetal craniofacial growth and development in utero, but in addition, it will help to make the diagnoses of mild craniofacial anomalies that would not be detected by the routine ultrasonographic examination. We suggest that this procedure should be included if not in all routine obstetrical ultrasound evaluations, then at least in the more extensive level II obstetrical ultrasound. PMID- 2197297 TI - Muscle stretching as an alternative relaxation training procedure. AB - The purpose of this program of research was to explore the use of muscle stretching procedures in relaxation training with a clinical population. In the first controlled study, stretching exercises for four muscle groups (obicularis occuli, sternocleidomastoid/trapezius, triceps/pectoralis major, and forearm/wrist flexors) were prepared. A group of people using these procedures (SR, N = 8) was compared to a group using the Bernstein and Borkovec (1973) tense release (TR; N = 8) techniques for those same muscle groups, as well as compared to an appropriate group of controls (WL; N = 8). Assessment of physiological (multi-site EMG) and subjective (emotions, muscle tension, and self-efficacy) responses showed that persons in the SR displayed less sadness, less self reported muscle tension at four sites, and less EMG activity on the r.masseter than persons in the TR group. In the second study, 15 subjects were administered an expanded version of the SR relaxation procedures. Results showed that all subjects reported significant decreases in self-reported levels of muscle tension; muscle tension responders showed lowered trapezius EMG and respiration rates and cardiovascular responders showed lowered diastolic blood pressure. The results are discussed in terms of the utility of relaxation procedures based primarily on muscle stretching exercises for lowering subjective and objective states of arousal. PMID- 2197299 TI - Dentin bonding. PMID- 2197298 TI - Effect of biofeedback assisted relaxation training on blood glucose levels in a type I insulin dependent diabetic. A case report. AB - Treatment of unstable Type I insulin dependent diabetes in a female client using relaxation training, biofeedback and stress management is described. Both average and standard deviation of blood glucose values decreased during treatment and improvements were maintained at one year follow-up with constant or slightly decreased insulin dosage. The results are discussed in the light of describing factors which may predispose diabetics to success in relaxation based treatment programs. PMID- 2197300 TI - Development and breakdown of written language. AB - This article presents an overview of the development and breakdown of written language. Development of written language is reviewed for both the species and the child. Breakdown in written language is discussed in relation to the disorder of linguistic agraphia, with particular reference to studies involving cases that have resulted from a cerebral vascular accident. It is hoped that the juxtaposition of these perspectives of development and breakdown of written language may act as a catalyst for new research endeavors. PMID- 2197301 TI - A method of assessing the written language of hearing-impaired students. AB - A carefully conceptualized and well-organized evaluation system can provide important information about students' writing abilities. By measuring students' skill proficiency before instruction, teachers can begin a program with an accurate picture of their students' strengths and areas of concern in writing. This article presents an overview of several ways to assess written language. In addition, it provides a rationale and method for assessing the written expression of hearing-impaired individuals that reflects all facets of the writing product and guides instruction in the writing process. PMID- 2197302 TI - Heterogeneity of keratinocytes in the epidermal basal cell layer. PMID- 2197303 TI - Use of 1M NaCl split skin in the indirect immunofluorescence of the linear IgA bullous dermatoses. AB - We compared 1M NaCl split skin with intact skin as substrates for detection of circulating IgA anti-basement membrane (BMZ) antibodies in linear IgA dermatosis (LAD). The sera of 63 patients with LAD including 27 adults and 36 with chronic bullous dermatosis of childhood (CBDC) were examined. 62% of patients overall had circulating IgA anti-BMZ antibodies detectable on intact skin. 73% of patients had circulating antibodies detectable on 1M NaCl split skin as an additional 7 sera were positive. This was a statistically significant increase (p less than 0.01). The sera were mostly positive at a higher titre on the split skin when compared with intact skin. On routine indirect immunofluorescence (IIF) all positive sera produced linear fluorescence on the epidermal side of the split. Twenty serum samples were incubated with split skin overnight; 4 of these specimens exhibited linear fluorescence on the epidermal and dermal sides of the split after this prolonged incubation. These findings suggest that 1M NaCl split skin is a more sensitive substrate for detection of circulating IgA anti-BMZ antibodies in LAD, that these antibodies are heterogeneous and that the target antigen has an epidermal component. PMID- 2197304 TI - Immunohistochemical classification of cutaneous pseudolymphomas: delineation of distinct patterns. AB - Because of the broad spectrum of clinical and histological features, cutaneous pseudolymphomas are difficult to classify. To delineate objective criteria for classification, we investigated the immunoarchitecture of 53 cases of pseudolymphomas; 29 were classified as T cell pseudolymphomas. The immunohistologic characteristics were the absence of B cell compartments, the predominance of T helper-inducer cells and the presence of Langerhans cells/indeterminate cells. Lymphomatoid contact dermatitis showed the bandlike (superficial) T cell pattern. Lymphocytic infiltration of the skin, lymphomatoid papulosis, lymphomatoid drug reactions, and persistent nodules following assaults by arthropods revealed a nodular T cell pattern. Twenty-four cases represented B cell pseudolymphomas containing a nodular arrangement of B lymphocytes. In 6 lesions, there were B cell aggregates without the association of dendritic reticulum cells (non follicular B cell pattern); in 18, the B cell clusters were associated with dendritic reticulum cells and a typical expression of IgM and IgD, thus forming fully developed germinal centers (follicular B cell pattern). The B cell clusters were always surrounded by distinct T zones. B cell patterns were present in lymphadenosis benigna cutis, large cell lymphocytoma and occasionally, in persistent nodules, following assaults by arthropods. PMID- 2197305 TI - A clinical review of preventive resin restorations. AB - Since the 1981-1982 academic year, the University of Iowa Department of Pediatric Dentistry had placed approximately 2000 composite/sealants or preventive resin restorations in children's molars. When these children appeared again for examination or treatment, their restorations were evaluated for retention, maintenance, and quality. Results were encouraging: more than 80 percent of the sealant material was "all present"; and more than 98 percent of the composite restorative material was rated quite satisfactory (the "Alfa" category). PMID- 2197306 TI - Idiopathic odontoma formation following avulsion of immature permanent incisors: two case reports. AB - From the findings of Case 1 and those cases reviewed in the literature it would appear that overfilling a canal with gutta percha prevents continued root formation after reimplantation of the tooth. The canal should be underfilled, therefore, if gutta percha is used as the obturating medium. Consequently, the authors recommend that calcium hydroxide be used as the root canal filling material of choice after reimplanting immature permanent teeth subsequent to traumatic avulsion. Since, however, calcium hydroxide paste tends to be resorbed, periodic refilling of the canal with the paste is required. Case 2 emphasizes the importance of periodic postoperative radiographic evaluation for several years after traumatic avulsion of immature permanent teeth. PMID- 2197307 TI - Temperature elevation generated by a focused Gaussian ultrasonic beam at a tissue bone interface. AB - When a focused Gaussian ultrasonic beam in soft tissue normally impinges on the boundary of a contiguous bone, reflection and transmission occur. Taking account of the reflection, the steady-state temperature elevation along the beam axis for this case was calculated. The effect of perfusion is also included. PMID- 2197308 TI - References to contemporary papers on acoustics. PMID- 2197309 TI - Guidelines for the early management of patients with acute myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee to Develop Guidelines for the Early Management of Patients with Acute Myocardial Infarction) PMID- 2197310 TI - Percutaneous coronary laser balloon angioplasty: initial results of a multicenter experience. AB - A multicenter clinical trial was initiated to test the potential safety and short term efficacy of a percutaneous coronary application of laser balloon angioplasty, which has been shown experimentally to alleviate the common causes (dissection, recoil, thrombus) of suboptimal luminal results of conventional balloon angioplasty. Fifty-five patients, the majority (62%) of whom had relatively high risk lesions, were treated in 10 centers with a laser balloon that was identical in size (3 x 20 mm) to a balloon used for conventional balloon angioplasty performed on the same lesion immediately before laser balloon angioplasty. One or more neodymium:yttrium aluminum garnet (Nd:YAG) (1,060 nm) laser doses of 250 to 450 J were each delivered over a 20 s duration per exposure. Immediately and 1 day after laser balloon angioplasty no significant adverse effects on the arterial lumen were noted in any patient. By computerized image analysis of cineangiograms initial conventional balloon angioplasty failed to achieve a minimal luminal diameter greater than 1.5 mm in 14 patients (25%), including 3 patients with acute closure. However, after subsequent laser balloon angioplasty, minimal luminal diameter exceeded this value in all patients including this subgroup. Overall, minimal luminal diameter increased from 1.74 +/ 0.46 mm after conventional balloon angioplasty to 2.32 +/- 0.31 mm after laser balloon angioplasty (p less than 0.001) with no change found on 1 day and 1 month follow-up angiograms. Thus, laser balloon angioplasty is a safe, effective procedure for improving luminal dimensions after conventional balloon angioplasty. PMID- 2197311 TI - Ischemic heart disease: the old versus the new. PMID- 2197312 TI - Safety and efficacy of a new transpulmonary ultrasound contrast agent: initial multicenter clinical results. AB - Myocardial contrast echocardiography has been found to be a safe and useful technique for evaluating relative changes in myocardial perfusion and delineating areas at risk. Although earlier contrast agents required direct delivery into the coronary arteries or aortic root, a new echocardiographic contrast agent, sonicated albumin microspheres (Albunex), has been found to cross the pulmonary circulation in experimental models. To determine the safety and preliminary efficacy of intravenous injections of Albunex in humans, 71 patients at three independent medical institutions underwent two-dimensional echocardiographic examination before, during and after the administration of three intravenous doses of Albunex, ranging from 0.01 to 0.12 ml/kg body weight. All patients provided a complete history and underwent physical and neurologic examination and laboratory and electrocardiographic evaluation before the injections; all evaluations (except for the history) were repeated at 2 h and 3 days after the injections of Albunex. The efficacy of the injections was qualitatively assessed by two independent blinded observers using a grading system of 0 to +3, with 0 indicating an absence of contrast effect and +3 indicating full opacification of the cavities examined. All injections were well tolerated and no serious side effects were noted in any of the patients. Irrespective of dose group, a cavity opacification greater than or equal to +2 was seen in the right ventricle in 212 (88%) of 240 injections and in the left ventricle in 151 (63%) of 240 injections as judged by the independent observers. The degree of ventricular cavity opacification appeared to be dose and concentration related.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2197313 TI - Endothelial cell dysfunction: an emerging endocrinopathy linked to coronary disease. PMID- 2197314 TI - Long-term nifedipine unloading therapy in asymptomatic patients with chronic severe aortic regurgitation. AB - Vasodilating agents acutely reduce regurgitant volume and improve left ventricular performance in aortic regurgitation, but more information is necessary about their long-term efficacy. To evaluate the effects of 12 months of therapy with nifedipine, a randomized, double-blind, placebo-controlled trial was performed in 72 asymptomatic patients with severe aortic regurgitation. At 12 months, patients receiving nifedipine had a significant reduction in left ventricular end-diastolic volume index (110 +/- 19 versus 136 +/- 22 ml/m2, p less than 0.01) and mass (115 +/- 19 versus 142 +/- 16 g/m2, p less than 0.01) measured by two-dimensional echocardiography. They also had a reduction in left ventricular mean wall stress (360 +/- 27 versus 479 +/- 36 kdyne/cm2, p less than 0.001) and an increase in ejection fraction (72 +/- 8% versus 60 +/- 6%, p less than 0.05). These data show that the long-term unloading action of nifedipine is able to reverse left ventricular dilation and hypertrophy and suggest that such therapy has the potential to delay the need for valve replacement in asymptomatic patients. PMID- 2197315 TI - Vasodilator therapy in chronic severe aortic regurgitation. PMID- 2197316 TI - Transesophageal echocardiography in children with congenital heart disease: an initial experience. AB - Transesophageal echocardiography with a single plane (transverse axis), dedicated pediatric probe was performed prospectively in 25 anesthetized children undergoing routine cardiac catheterization or intracardiac surgery, to assess the potential role of this technique in the initial diagnosis, perioperative management and postoperative follow-up of children with congenital heart disease. The group ranged in age from 1 year to 14.8 years (mean 6.1) and weight from 6.5 to 52 kg (mean 22.4). Studies were successful in all patients and no complications were encountered. The results of the transesophageal studies (combined imaging, color flow mapping and pulsed wave Doppler sampling) were correlated both with the results of prior precordial studies and the information obtained at cardiac catheterization. Transesophageal echocardiography provided a more detailed evaluation of the morphology and function of systemic and pulmonary venous return, the atria, interatrial baffles, atrioventricular valves and the left ventricular outflow tract. Additional information was obtained in 15 patients (60%). Problem areas for single plane transesophageal imaging were the apical interventricular septum, the right ventricular outflow tract and the left pulmonary artery. The intraoperative use of transesophageal echocardiography allowed assessment of the surgical repair and monitoring of ventricular function and volume status while the patient was weaned from cardiopulmonary bypass. Transesophageal echocardiography in pediatric patients is of additional value in three main areas: 1) the precise morphologic diagnosis of congenital heart disease, 2) perioperative monitoring, and 3) postsurgical follow-up. PMID- 2197317 TI - Transesophageal echocardiography in children: new peephole to the heart. PMID- 2197318 TI - Factors influencing choice of procedure in transposition of the great arteries: a decision analysis approach. AB - Clinicians have a difficult choice between the arterial switch (Jatene et al.) and the atrial baffle operation (Mustard or Senning) for transposition of the great arteries. The surgical decision is essentially a determination of whether the long-term course after the arterial switch procedure (thought to be more favorable than after the atrial baffle procedure) plus elimination of presurgical attrition with the atrial baffle is substantial enough to offset the higher early mortality rate associated with the arterial switch. Decision analysis was undertaken to answer the following questions: 1) are there clinical circumstances under which published surgical results support a clear procedure of choice in transposition of the great arteries? and 2) what short- and long-term outcomes must be anticipated for the arterial switch to compare favorably with the published experience with the atrial baffle? A decision tree was constructed accounting for the major variables influencing mortality and morbidity in the surgical management of transposition of the great arteries. Presuming that the arterial switch has moderate advantages over the atrial baffle in terms of late morbidity and mortality for simple transposition of the great arteries at an institution with average results from the atrial baffle, the early mortality rate of the arterial switch must be less than 24% to recommend the switch operation. Assuming extremely good surgical results from the atrial baffle, an early mortality rate of the arterial switch less than 20% is required to recommend the switch procedure over the atrial baffle operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2197319 TI - Wanted: dead or alive--the search for markers of myocardial viability. PMID- 2197320 TI - Multicenter HIV and hepatitis B seroprevalence study. AB - Prior single institutional investigations have found unrecognized HIV seroprevalence in emergency department (ED) patients to range from 0.38% to 4%. A prospective, anonymous study of HIV and hepatitis B (HB) seroprevalence was performed on excess serum of all ED patients over two 48-hour periods in May and August, 1988, from 7 hospitals in the Portland metropolitan area. Demographics were known for 338/444 (76%) of patients. Forty-six percent were male, 85% white, with a median age group of 30-39 years. Ambulance transport, trauma, external blood, presentations requiring ED procedure(s), and acuity resulting in ICU admission were present on 21%, 7%, 10%, 34%, and 14% of patients, respectively. Two of 444 (.45%) patients were HIV +, one previously undiagnosed. Fifty-five of the 444 (12%) and 3 of 444 (0.6%) samples were positive for HBcAB and HBsAG respectively. Risk factor assessment was possible on 180/444 (40%) patients. HBcAB seroprevalence correlated with race (P less than 0.01), IV drug use (P less than 0.0001), and hospital location, (P less than 0.006) but were sensitive in detecting only 14%, 18%, and 38%, respectively, of HBcAB+ patients. HBcAB was not associated with the following factors: sex, area of residence, presence of blood externally, trauma, acuity of illness, ED procedures, or mode of transport. This data strongly support the use of universal body fluid precautions. Hepatitis B poses a significant and distinct risk to all emergency care providers. HB vaccination should be strongly advocated for all ED health care workers (HCWs). Emergency medicine multicenter studies are both desirable and feasible. PMID- 2197321 TI - A beveled, conventional cutting edge surgical needle: a new innovation in wound closure. AB - A new beveled, conventional cutting edge needle has been developed with superior performance characteristics over those of other conventional cutting edge needles. It is composed of a unique stainless steel, ASTM 45500, that has been heat-treated after the curving process to enhance its resistance to bending. The angle of presentation of its cutting edges has been decreased to enhance needle sharpness. On the basis of the results of experimental and clinical investigations, this new needle is recommended for closure of lacerations. PMID- 2197322 TI - Functional airway obstruction presenting as stridor: a case report and literature review. AB - We report the case of a young man who presented to 3 emergency departments with apparent upper airway obstruction and was intubated each time before being diagnosed with paradoxical vocal cord motion. His previous discharge diagnoses were laryngeal edema secondary to anaphylaxis, even though he had no other objective findings of IgE-mediated disease. Flexible fiberoptic laryngoscopy demonstrated tight apposition of the vocal cords during inspiration while symptomatic, but normal movement when asymptomatic. Psychiatric evaluation revealed severe posttraumatic stress disorder. Of the approximately 41 reported cases of functional airway obstruction in the medical literature, only two have been adult males and none have been associated with posttraumatic stress disorder. The current literature is reviewed, and an approach to evaluation and management of such patients is provided. PMID- 2197324 TI - Strychnine poisoning. AB - Strychnine poisoning is an unusual but dramatic poisoning in which convulsions are the major threat to life. Convulsions are predominantly at the spinal level, and the key to recognition of this poisoning is observation of convulsive activity in the awake patient without a postictal phase. Successful treatment requires aggressive airway control and treatment of seizures with benzodiazepines or barbiturates. Neuromuscular blockade may be required. Gastrointestinal decontamination is usually indicated in recent acute ingestions but may precipitate convulsions. Recovery from strychnine poisoning is usually complete and rapid if treatment is aggressive. In the absence of trauma, compartment syndrome, rhabdomyolysis, or anoxic central nervous system injury, no neurologic or musculoskeletal sequelae are expected. Confirmation of strychnine poisoning is best obtained by submitting urine or gastric aspirate for analysis utilizing a qualitative test such as thin layer chromatography (TLC). PMID- 2197323 TI - Iron poisoning: report of three cases and a review of therapeutic intervention. AB - Although the acute ingestion of iron-containing preparations can produce very serious consequences, the majority of reported exposures are not associated with significant morbidity or mortality. We present 3 cases of acute iron ingestion and review the aspects of general management, with an emphasis on the appropriate choice of a gastrointestinal decontamination procedure. PMID- 2197325 TI - Human T-cell lymphotropic virus-type I. AB - HTLV-I is a retrovirus now identified as the etiologic agent of two diverse disease processes: ATLL, an aggressive T-cell malignancy; and TSP/HAM, a chronic progressive myelopathy. Transmission can occur horizontally through blood transfusions, IV drug abuse and sexual intercourse. Vertical transmission may also occur. Available diagnostic modalities are serologic in nature and include the EIA and the more specific confirmatory assays WIB and RIPA. These studies are thus far suboptimal in terms of sensitivity and specificity, and await refinement. DNA amplification by the polymerase chain reaction seems to hold the most immediate diagnostic promise for the future. AZT apparently is not useful clinically, and current treatment is only palliative in nature. The diverse diseases caused by HTLV-I underscore the insidious nature of the Retroviridae family. These subtle cell-associated pathogens will undoubtedly be shown to play a significant role in other disease processes of uncertain etiology. PMID- 2197326 TI - The management and treatment of an abnormal Pap smear. AB - Table 2 summarizes the management of the abnormal Pap smear. Management of dysplasia in this institution is aggressive--as destructive therapy of mild dysplasia is advised, opposed to watching the patient and treating only if the disease persists. The rationale for this is the 33% to 45% failure rate for follow-up appointments in the primarily inner-city population served. The key to follow-up is to repeat cervical cytology in all patients treated, even those treated with hysterectomy, every three months until two consecutive normal smears are obtained. At that time, surveillance and intervals may be modified, but screening should continue at least annually. The mortality rate of carcinoma of the cervix has dropped precipitously during the last 40 years, in part, from simple screening of the cervix with the Papanicolaou smear. The effort to treat premalignant changes has been rewarded. The use of the colposcope and destructive forms of therapy have allowed successful treatment of patients with less morbidity and mortality than the immediate reliance on cervical conization. Remember, conization is still indicated and prudent in selected patients. Following these guidelines may contribute to the downward trend. PMID- 2197327 TI - Processing surgically removed lymph nodes. AB - Delicate lymph nodal tissue must be processed accurately and evaluated for proper patient management. In more than 125 cases at Methodist Hospital of Indiana, we devised a procedure that has allowed accurate diagnosis in 98% of cases. The pathologist's approach and the variety of studies necessary to confirm the diagnosis are presented, as well as important procedural considerations. PMID- 2197328 TI - The role of the physician in identifying and treating abused women. AB - The physician can identify abuse when probable or suspicious symptoms are presented. Interviewing and assessment techniques that help the patient disclose her abuse and make positive use of referral sources are discussed and illustrated. Identification of the abuse is the first step for most victims as they struggle toward social and psychological rehabilitation. PMID- 2197329 TI - Post-transcriptional regulation of granulocyte-macrophage colony-stimulating factor synthesis in murine T cells. AB - The granulocyte-macrophage CSF (GM-CSF) gene is known to be controlled at a variety of levels in different cell types. We showed previously that GM-CSF production by lectin or phorbol ester (12-O-tetradecanoyl-phorbol-13-acetate (TPA]-treated T cells was unaffected by cyclosporin A whereas IL-2 and IL-3 expression were. Cyclosporin A is thought to inhibit transcription that suggests that IL-2 and IL-3 are regulated primarily at the transcriptional level while GM CSF is not. The lack of coordinate gene expression is of particular interest because all three mRNA share the presence of adenosine uridine-rich sequences in the 3' untranslated region and these sequences are believed to act by modulating mRNA stability. We measured the level of GM-CSF mRNA in untreated cells and found it to be extremely low. GM-CSF mRNA levels increased approximately 60-fold within 6 h of TPA-treatment. Nuclear run-on transcription analysis of the same cells showed readily detectable GM-CSF transcription in unstimulated cells that increased less than twofold after TPA treatment. However, IL-2 transcription was insignificant before TPA addition. Actinomycin D chase experiments showed that GM CSF transcripts in untreated cells have a very short half-life (approximately 45 min) although transcripts in TPA-treated cells have a half-life exceeding 3 h. These findings indicate that GM-CSF production in EL-4 cells treated with TPA is regulated predominantly by modulation of cytoplasmic mRNA half-life. PMID- 2197330 TI - Determination of mixed chimerism by a simple flow cytometry method. AB - A simple, sensitive and accurate method was developed to determine the level of lymphoid chimerism in bone marrow-transplanted rodents. The method is based on flow cytometry using polyclonal alloantisera and labeled second step anti-IgG antibodies. Using mixtures of spleen cells from different mouse strains, it was demonstrated that low levels of chimeric cells (less than 1%) could easily be detected. Moreover, using two-color fluorescence analysis, the level of chimerism could also be determined in subpopulations of lymphoid cells, e.g., CD4 or CD8 cells and was found to be identical to the results obtained in unseparated lymphoid populations. The method was compared to the complement dependent cytotoxicity assay (CDCA) and to the flow cytometric determination of chimerism using labeled monoclonal antibodies against specific MHC antigens. CDCA was found to be more labor intensive and could only estimate the composition of the cell mixtures without detecting low levels of chimerism (less than 5%). The results of flow cytometry, using directly labeled monoclonal antibodies or polyclonal antibodies with second step reagents, were identical. It is concluded that, due to its simplicity and high sensitivity, the method described permits reliable determination of the level of mixed chimerism in rodents and is an excellent alternative when no anti-MHC mAbs are available. PMID- 2197331 TI - Quantitation of polymorphonuclear leukocyte adherence to endothelial cells by electronic particle size discrimination. AB - A method for quantitating the number of polymorphonuclear leukocytes (PMNs) adhering to endothelial cells in vitro is presented. Confluent human umbilical vein endothelial cells cultured in 24-well multiplates and treated with tumor necrosis factor alpha (TNF alpha) were incubated subsequently with PMNs which adhere to the endothelial cell as a function of TNF alpha concentration. Adherent PMNs and endothelial cells were proteolytically dissociated from the multiwell and, using an electronic particle counter, the number of endothelial cells and PMNs were determined simultaneously on the basis of size. The average number of PMNs adhering per endothelial cell was then calculated. The method is rapid and precise and offers an alternative to both tedious microscopic counting and the hazardous radiolabeling of PMNs. PMID- 2197332 TI - Microenzyme immunoassay for the measurement of brain natriuretic peptide (BNP) like immunoreactivity in porcine plasma. AB - A sensitive and specific microenzyme immunoassay (EIA) procedure for porcine brain natriuretic peptide (BNP)-like immunoreactivity has been developed. Enzyme labeled antigen was prepared by conjugation of synthetic BNP with beta-D galactosidase using N-(epsilon-maleimidocaproyloxy)succinimide method. Using a second antibody-coated immunoplate, the minimum amount of BNP-like immunoreactivity (BNP-LI) detectable by this assay system was 1.6 fmol/well. When porcine BNP-LI in porcine plasma was assayed by the present method levels between 1 and 8 pmol/l were detected. Gel filtration of porcine plasma extracts on Sephadex G-25 revealed the presence of two immunoreactive peaks; one eluted at a position identical with that of BNP-26 and the other eluted earlier, close the position of BNP-32. PMID- 2197333 TI - An improved double fluorescence flow cytometry method for the quantification of killer cell/target cell conjugate formation. AB - We have developed an improved method to analyse stable associations (conjugate formation) between effector and target cells. Hydroethidine (red) stained lymphoblastoid target cells were cocentrifuged with carboxyfluorescein diacetate acetoxymethylester (green) stained human IL-2 activated cytotoxic cells (LAK). In the present studies either enriched or purified CD3 negative large granular lymphocytes (LGL) were used as cytotoxic cells. These fluorescent vital dyes localize intracellularly and therefore do not modify the cell to cell contact which eventually leads to the lytic events. Both dyes can be excited at a common wavelength (488 nm) using a single argon laser. Effectors firmly bound to target(s) (stable conjugates) were detected as two color fluorescent events (red and green). This method has several features: (a) the number of conjugates is recorded with reference to a fixed number of target cells; (b) the composition of conjugates (number of effectors or targets per conjugate) can be studied by analysis of the fluorescence intensities (red or green); (c) conjugate formation can be studied at E:T ratios comparable to those used in the classical 51Cr release cytotoxic assay; (d) it gives reproducible results and permits the study of very weak differences in binding properties. This method was used to study conjugate formation between human IL-2-activated cytotoxic cells (or purified CD3 negative LGL) and various lymphoblastoid target cells. We were able to demonstrate that cell lines susceptible to lysis formed more conjugates and were surrounded by more LAK effectors than their resistant counterparts and that no conjugate contained more than one target. PMID- 2197334 TI - Regeneration of immunosorbent surfaces used in clinical, industrial and environmental biosensors. Role of covalent and non-covalent interactions. AB - The durability and regeneration of antibodies immobilized to commercial immunosorbents were investigated by monitoring Ag-Ab dissociation. Solutions consisting of 0.01 M hydrochloric acid (HCl), 10% propionic acid, 50% ethylene glycol and 10% SDS in 6 M urea were used in the evaluation of antigen dissociation from antibody covalently immobilized to glass and polystyrene beads, microtiter plates and Immobilon filters. RAH-IgG, used as a model antibody, bound strongly to all covalent surfaces. However, on adsorption to Nunc-1 microtiter plates, 25-60% of RAH-IgG was removed by all dissociating solutions. Covalent binding to Sanger beads was weakest relative to other covalent surfaces, exhibiting 30% and 65% detachment with ethylene glycol and SDS in urea, respectively. Although all four solutions dissociated antigen from surface-bound antibody, HCl and propionic acid were more effective on most surfaces. The antibody remained functional following antigen dissociation and reassociated to nearly 100% on all surfaces except Sanger beads and Nunc-1 microtiter plates. This study was initiated to evaluate regeneration and reuse of microelisa plates and emerging biosensors as a means of reducing routine laboratory analysis costs. Data are presented to demonstrate the reusability of microtiter plates in ELISAs following antigen dissociation from covalently bound antibody. PMID- 2197335 TI - Comparison of live attenuated cold-adapted and avian-human influenza A/Bethesda/85 (H3N2) reassortant virus vaccines in infants and children. AB - Randomized, placebo-controlled studies with 10(3)-10(7) 50% tissue-culture infectious dose (TCID50) of avian-human (ah) and cold-adapted (ca) influenza A/Bethesda/85 (H3N2) reassortant viruses were completed in 106 seronegative young children 6-48 months of age. Although the reassortants differed in six of eight RNA segments, they exhibited similar properties in level of attenuation, infectivity, immunogenicity, and efficacy. The 50% human infectious dose was 10(4.6) TCID50 for ah and 10(4.4) for ca vaccines. Both reassortants were satisfactorily attenuated with restricted replication and were no more reactogenic than placebo. The mean peak titer of virus shed was 10(1.5) (ah) to 10(2.0) (ca) TCID50/ml, and each of 37 isolates tested retained their characteristic vaccine phenotypes. Infection with ah or ca virus conferred immunity to experimental challenge with homologous virus. These findings indicate that both ah and ca influenza A/Bethesda/85 (H3N2) reassortants should be suitable vaccine candidates for use in healthy infants and young children. PMID- 2197336 TI - Bacteroides lipopolysaccharides (LPS) induce anaphylactoid and lethal reactions in LPS-responsive and -nonresponsive mice primed with muramyl dipeptide. AB - Lipopolysaccharides (LPS) (100 micrograms/mouse) from Bacteroides gingivalis elicited anaphylactoid reactions in N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) (100 micrograms)-primed C3H/HeN mice 0-48 h after MDP injection. The reaction resulted in death within 1 h when the LPS was injected 2-10 h after the MDP injection. LPS prepared from other Bacteroides and Salmonella species but not from others, including Escherichia coli, could induce the reaction. LPS nonresponsive C3H/HeJ and C57BL/6 and C57BL/10 strains were also responsive to the reaction, while AKR, BALB/c, DBA/2, and ICR mice were not. By contrast, Bacteroides LPS exhibited weak lethal toxicity compared with E. coli LPS in galactosamine-sensitized C3H/HeN mice, while neither LPS had activity in C3H/HeJ mice. LPS from E. coli and Bacteroides intermedius induced serum tumor necrosis factor (TNF) activity in MDP-primed mice, except for C3H/HeJ mice; B. gingivalis LPS rarely induced TNF in C3H/HeN or C3H/HeJ mice, indicating no involvement of TNF in the anaphylactoid reaction. Serotonin could substitute for MDP for the reaction, and methysergide, a serotonin antagonist, inhibited the activity. PMID- 2197337 TI - Seroepidemiologic evaluation of anti-toxic and anti-colonization factor immunity against infections by LT-producing Escherichia coli in rural Bangladesh. AB - To evaluate serologic immunity against clinical infections by heat-labile enterotoxin-producing Escherichia coli (LT-ETEC) in rural Bangladesh, 124 children and adult women with LT-ETEC diarrhea (cases) were compared with 347 age matched community controls. In paired acute-convalescent sera from the cases, IgG anti-CFA I and anti-CFA II antibody titers increased eight-to ninefold after infection by LT-ETEC with the homologous CFA, and IgG anti-LT antibody titers increased fourfold for all LT-ETEC infections. Anti-CFA and anti-LT titers peaked in controls aged 12-23 months, the age group with the highest incidence of ETEC infections. However, antibody titers were similar in acute sera from cases and in sera from controls. Although serum IgG anti-CFA and anti-LT antibodies rose in response to LT-ETEC infections and paralleled the age-specific incidence of ETEC in the community, these antibodies were not associated with a lower risk of LT ETEC diarrhea. PMID- 2197338 TI - Monoclonal antibody to endotoxin core protects mice from Escherichia coli sepsis by a mechanism independent of tumor necrosis factor and interleukin-6. AB - To study the role of cytokines as mediators of endotoxin-induced shock, the serum levels of tumor necrosis factor (TNF) and interleukin-6 (IL-6) were compared in mice receiving either a monoclonal antibody to endotoxin core (clone 20), an irrelevant monoclonal antibody (A1), or culture media (DMEM/FCS) alone before lethal challenge with live Escherichia coli O111:B4. Clone 20 given 1.5 h before the bacterial challenge protected mice from death (mortality at 48 h 3% vs. 87%, P less than .001). The pattern of IL-6 release was indistinguishable in clone 20 recipients and controls: The area under the curve (AUC) for 5 h was 1.22 +/- 0.07 x 10(6), 1.03 +/- 0.17 x 10(6), and 1.22 +/- 0.07 x 10(6) units/ml for clone 20, A1, and DMEM/FCS, respectively. Similarly, the timing and extent of TNF release in the serum was virtually identical in clone 20 recipients that survived and control animals that died. AUC for 5 h was 30.8 +/- 4.0 x 10(3), 28.1 +/- 1.1 x 10(3), and 30.4 +/- 4.7 x 10(3) ng/ml in clone 20, A1, and DMEM/FCS recipients, respectively. Thus, TNF and IL-6 appear insufficient to cause death in this model of experimental gram-negative shock. PMID- 2197339 TI - A novel chromosomal TEM derivative and alterations in outer membrane proteins together mediate selective ceftazidime resistance in Escherichia coli. AB - A clinical Escherichia coli isolate (MG32) resistant to ceftazidime but susceptible to other third-generation cephalosporins was previously examined and found to harbor TEM-1 and exhibit alterations in outer membrane proteins. Reexamination of this isolate revealed the additional presence of a novel TEM-1 derivative, now designated TEM-12. Evaluation of ceftazidime and cefotaxime minimum inhibitory concentrations for isogenic derivatives demonstrated a major role for TEM-12 in the decreased susceptibility observed. This was selectively enhanced for ceftazidime resistance by the altered porins of E. coli MG32. TEM-12 appeared identical to TEM-101, an in vitro TEM derivative, in both isoelectric point (pI 5.25) and substrate profile. Hybridization and cloning of the TEM-12 determinant revealed that, unlike other TEM derivatives, TEM-12 is chromosomally encoded, not plasmid-encoded. PMID- 2197340 TI - Novel dihydrofolate reductases isolated from epidemic strains of trimethoprim/sulfamethoxazole-resistant Shigella sonnei. AB - Two strains of trimethoprim-resistant Shigella sonnei bearing R plasmids pBH600 and pBH700 each elaborated a dihydrofolate reductase (DHFR) and were moderately resistant to trimethoprim (minimum inhibitory concentrations, 128 and 256 micrograms/ml, respectively). Neither plasmid hybridized to probes for DHFR types I, II, or III. The trimethoprim resistance genes from the R plasmids resided on a 1600-base pair (bp) PstI fragment of pBH600 and an 1800-bp PstI fragment of pBH700. Isoelectric focusing showed distinct isoelectric points for the enzymes coded for on pBH600 (5.3) and pBH700 (5.6-5.7). Trimethoprim-resistant S. sonnei from 10 locations in nine states were examined. Isolates from 8 locations hybridized only to a pBH700-derived probe and one isolate hybridized to a pBH600 derived probe. These two trimethoprim resistance genes appear novel. The gene on plasmid pBH700 codes for an enzyme that seems widespread among S. sonnei isolates in the USA. PMID- 2197341 TI - Role of complement receptors in opsonophagocytosis of group B streptococci by adult and neonatal neutrophils. AB - The role of complement receptors in bactericidal activity for types III and Ia group B streptococci (GBS) by adult or neonatal polymorphonuclear leukocytes (PMNL) was explored using polyclonal and monoclonal antibodies to complement receptors one (CR1) and three (CR3). In an opsonophagocytic assay, selective blockade of the CR3 sugar or lectin-like binding site on adult or neonatal PMNL effected a significant reduction in killing of both GBS serotypes that was more pronounced for type III. In contrast, blockade of the iC3b binding site effected greater inhibition of bactericidal activity for type Ia than for type III GBS. When both the CR3 sugar or lectin-like binding site and CR1 were blocked, inhibition was enhanced for type Ia GBS by adult PMNL and for both serotypes by neonatal PMNL. These results demonstrate a role for both CR1 and CR3 in the opsonophagocytosis of GBS. Possibly, differences in CR3 epitope utilization contribute to the differential virulence among GBS serotypes in neonates. PMID- 2197342 TI - Response to tetanus toxoid immunization after allogeneic bone marrow transplantation. AB - An ELISA was used to study long-term immunity and immunization responses to tetanus toxoid in 48 bone marrow transplant recipients. Among patients who were seropositive to tetanus before transplant, 51% had lost their seropositivity 1 year later. All patients who were not reimmunized with tetanus toxoid were seronegative 2 years after transplant. All patients who were seronegative before transplant remained seronegative 1 year later regardless of the donor's serologic status. There was no difference in the ability to remain seropositive to tetanus toxoid between patients with and without chronic graft-versus-host disease. Of 21 patients immunized with one dose of tetanus toxoid 1 year after transplant, 14 were seronegative at the time of immunization (response rate, 64%). At 1 year after immunization, 7 remained seropositive. Ten patients were reimmunized with two doses of tetanus toxoid. All responded and 90% remained seropositive 1 year later. When 21 patients were primarily immunized with three doses of tetanus toxoid, all patients seronegative at immunization responded and all tested patients remained seropositive 2 years later. The immunization responses were significantly superior in patients receiving three doses compared with those who received one. Reimmunization with tetanus toxoid of long-term survivors after marrow transplant seems necessary. A three-dose immunization schedule is recommended to obtain an adequate immune response. PMID- 2197343 TI - Elevated antibody levels to mycobacterial 65-kDa stress protein in patients with superficial candidiasis. AB - Antibody levels to the mycobacterial 65-kDa stress protein (mSP65) were determined by ELISA in sera from patients with chronic atrophic oral candidiasis, vulvovaginal candidiasis, Candida albicans-infected or noninfected oral lichen planus, or recurrent aphthous ulceration and from subjects with clinically healthy oral mucosa. The results showed significantly elevated anti-mSP65 antibody levels in patients with oral or vulvovaginal candidiasis and in patients with Candida-infected lesions of lichen planus when compared with patients with noninfected lichen planus or recurrent oral ulceration and with matched healthy controls (P less than .001). Immunoblot analysis showed that the rabbit antiserum that strongly bound to mSP65 cross-reacted only weakly with a homologous band of a soluble C. albicans extract. Moreover, the binding of antibodies from patients with candidiasis to the mSP65 antigen was not inhibited in the presence of Candida extract. In view of the poor serologic cross-reactivity, it seems plausible that the recall stimulation of anti-mSP65-producing B cells could be induced by helper T cells that cross-react with the structurally homologous protein of C. albicans. PMID- 2197344 TI - Changes in antibody profile after treatment of human onchocerciasis. AB - To define the changes in antibody response to Onchocerca volvulus antigens after treatment of patients with onchocerciasis, IgG and IgE antibodies were examined quantitatively and qualitatively in 21 patients and 3 control individuals before and sequentially for 14 days after treatment with diethylcarbamazine. The quantitative levels of IgE and IgG responses (both polyclonal and O. volvulus specific) remained essentially unchanged for all patients, but 9 of the 21 patients showed intensified responses to one or more parasite-specific antigens, and 8 of 21 developed antibodies to previously undetected antigens. There was a significant correlation between the intensities of infection and the development of newly recognized anti-O. volvulus antibodies. These studies demonstrate that O. volvulus-specific IgE and IgG antibody responses are, at least transiently, enhanced by treatment with diethylcarbamazine and that after treatment, parasites possibly release antigens previously hidden from the host's immune response. PMID- 2197345 TI - Challenge studies in volunteers using Escherichia coli strains with diffuse adherence to HEp-2 cells. AB - Diffusely adherent (DA) Escherichia coli, a newly described category, has been associated with diarrhea in children in some but not all epidemiologic studies. To investigate its diarrheagenic potential, two strains of DA E. coli were fed to adult volunteers in doses of 10(5)-10(10) colony-forming units. None of 22 volunteers who received strain 57-1 or of 21 who received strain C1845 developed symptoms of diarrhea as defined for this study. All volunteers shed the challenge DA E. coli in their stools. Duodenal string cultures were positive in some volunteers only at the highest doses. Only 6 developed IgG or IgA antibodies to whole DA E. coli. Thus, the pathogenic potential of DA E. coli could not be shown in this model. Further studies are needed to characterize potential virulence factors of DA E. coli that might distinguish a pathogenic subset. PMID- 2197346 TI - Escherichia coli O157:H7 and the hemolytic uremic syndrome: importance of early cultures in establishing the etiology. AB - Fifty-two patients were studied prospectively to determine the etiology of postdiarrheal hemolytic uremic syndrome (HUS). Escherichia coli O157:H7 was isolated from 33 patients (63.4%). If stool obtained within 2 days of the onset of diarrhea was cultured for E. coli O157:H7, the recovery rate was 100%. This rate decreased to 91.7% and 33.3% if stool was cultured for this pathogen 3-6 or greater than or equal to 7 days, respectively, after diarrhea began. The culture positive group was more likely to have had bloody diarrhea and fecal leukocytes and to have received transfusions than the culture-negative group but was otherwise similar in clinical characteristics. E. coli O157:H7 is the predominant pathogen associated with HUS in western Washington. Recovery of this pathogen is highly dependent on obtaining stool cultures within 6 days of onset of diarrhea. PMID- 2197347 TI - Limulus lysate positivity and Herxheimer-like reactions in leptospirosis: a placebo-controlled study. AB - Jarisch-Herxheimer reactions are characteristic of some spirochetal diseases and have been reported in leptospirosis, but their pathogenesis and relationship to endotoxin remain unclear. Serial limulus amebocyte lysate assays (LAL) for endotoxin were performed on 40 patients with proven leptospirosis who were monitored for reactions after receiving either intravenous penicillin (24) or saline placebo (16). No Herxheimer-like reactions were observed, although 78% of patients had at least one positive LAL. Serum creatinine, serum bilirubin, and white blood cell counts were significantly higher (P less than .01) in simultaneously drawn LAL-positive specimens than in negative ones. Delayed hepatic clearance of endotoxin due to liver dysfunction may explain the high LAL positivity rate, since assay results correlated with severity of disease but not with the presence or absence of spirochetes. Fear of a Herxheimer-like reaction should not dissuade clinicians from administering antibiotics to patients with leptospirosis. PMID- 2197348 TI - Serologic evidence of respiratory syncytial virus infection in nursing home patients. PMID- 2197349 TI - [Surgical repair of total anomalous pulmonary venous connection in neonates and infants--prevention for pulmonary venous obstruction at the site of anastomosis]. AB - From October, 1980, to June, 1987, thirty-eight infants less than one year old underwent correction for total anomalous pulmonary venous connection (TAPVC). Overall operative mortality and late mortality were 13% and 6%, respectively. Residual pulmonary hypertension was noted in 4 patients: three had pulmonary venous obstruction at the site of atrial anastomosis (PVOA) and one had supracardiac (Ia) lesion left after repair of mixed type (IV: Ia + III) of TAPVC. Two late deaths occurred in these with PVOA. Twenty-two patients with supracardiac (I) or infracardiac (III) TAPVC were divided into three groups according to the technical development in atrial anastomosis: the large anastomosis in which venous incision reached into at least one pulmonary vein beyond common pulmonary vein and the continuous running suture were used in 10 patients (group 1), the appropriate size of anastomosis in which venous incision limited within the common pulmonary vein and the continuous running suture used in 4 patients (group 2), and the appropriate size of anastomosis and the interrupted suture in 8 patients (group 3). PVOA were 3 (33%) in group 1, but 0 (0%) in group 2 and 3. Two late death occurred all in group 1 with PVOA. Cardiopulmonary bypass time and aortic clamp time in group 3 were 91 min and 74 min respectively, which did not become longer than those in both group 1 and group 2. Interrupted suture technique does not make operating time longer than continuous running suture one. PVOA is one of the important factors predicting late operative result.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2197350 TI - [Konno procedure for congenital aortic valve stenosis with pulmonary valve stenosis]. AB - Although aortic and pulmonary valve stenosis are among the most common congenital heart defects, the combination of both aortic and pulmonary valve stenosis in the same patient appears to be very uncommon. Accurate diagnosis of combined valvular stenosis is imperative prior to surgical correction, otherwise surgery of one of the lesions may result in an insufficient hemodynamic improvement. A seven-year old girl with congenital aortic and pulmonary valve stenosis associated with hypoplastic aortic annulus underwent Konno's operation, pulmonary valvotomy and resection of anomalous muscle of the right ventricular outflow tract simultaneously. The operation was successfully performed and postoperative course was uneventful. PMID- 2197352 TI - [Biochemistry and Kant's philosophy the "Thing-in-itself]. PMID- 2197351 TI - [Intrapericardial bronchogenic cyst--a report of two surgical cases]. AB - Two cases of intrapericardial bronchogenic cyst are reported. Case 1 was a 58 year-old man with a complaint of exertional dyspnea. A chest X-ray film showed a right hilar mass shadow. Echocardiographically the mass showed cystic pattern in the pericardium. A pulmonary angiogram revealed a mass displacing the right pulmonary artery superiolaterally and left atrium and pulmonary vein inferiorly. The preoperative diagnosis was intrapericardial cyst. Subtotal resection of intrapericardial cyst was performed via right thoracotomy. Histological diagnosis was bronchogenic cyst. The postoperative course was uneventful. Case 2 was a 41 year-old man. A displacement of the esophagus and duodenal ulcer was pointed out in the upper gastrointestinal series. A chest X-ray film showed a right hilar mass shadow. Since echocardiogram and pulmonary angiogram revealed similar findings to those in case 1, intrapericardial bronchogenic cyst was suspected preoperatively. Complete resection of the intrapericardial cyst was made via right thoracotomy. Histological diagnosis was bronchogenic cyst. The postoperative course was uneventful. PMID- 2197353 TI - [Recognition mechanisms of receptor sialooligosaccharides by influenza virus hemagglutinin and sialidase]. PMID- 2197354 TI - [Recent progress in casein kinase research]. PMID- 2197355 TI - Soft tissue profile changes following orthodontic treatment of Chinese adults with Class III malocclusion. AB - Thirty-eight adult Chinese patients (mean age 24.3 +/- 3.2 years) exhibiting true Class III dental and skeletal malocclusions were treated orthodontically with the edgewise appliance and extractions of mandibular first premolars together with simultaneous anterior expansion of the maxillary arch. A retrospective cephalometric study was undertaken to determine the soft tissue profile changes at least 6 months postretention. Significant cephalometric changes included decrease in the mandibular incisor protrusiveness by 6.4 mm (P less than .001) and accompanying lower lip protrusiveness by 4.4 mm (P less than .01), together with a slight forward movement of the maxillary incisors by 1.7 mm (P less than .05) and, consequently, a slight increase in upper lip protrusiveness by 1.2 mm (P less than .05) and decrease in nasolabial angle (P less than .05). The overall improvement in lip profile provided by this mandibular arch contraction/maxillary arch expansion orthodontic approach appears to be a viable alternative in mild-to moderate Class III patients who decline orthognathic surgery. PMID- 2197356 TI - [Fundamental studies on the subrenal capsule assay as chemosensitivity test for nonsolid tumors]. AB - Fundamental evaluation of the subrenal capsule assay (SRCA) method in nonsolid tumors was made, using two types of murine malignant ascites. Malignant ascites were obtained from mice bearing M-5076 ovarian reticular cell sarcoma or MH-134 hepatoma. These tumor cells were allowed to settle by standing at 4 degrees C to form a jelly-like clot. This clot was cut into fragments about 1mm3 in size and one of these fragments was mashed in trypan blue to estimate the viability grade of the implanted tumor cells. The rest of the fragments were implanted beneath the renal capsule of the mice. On the 6th day after implantation, the assay mice were killed, the increase in the size of the tumor was determined and histological examination was carried out. The results were as follows: (1) The clot was formed reproductively by allowing ascites to settle for one or two days and there was a high viability rate for the tumor cells: 79.9 +/- 11.0% of M-5076 and 90.1 +/- 5.9% of MH-134. (2) The ascites clot thus implanted grew rapidly in the control groups but growth was inhibited by chemotherapy: Tumors were reduced significantly (p less than 0.05-0.005) in the group treated with a single agent. This trend towards a suppressive effect of carcinocidal agents on the tumor growth was more conspicuous as a combination regimen was utilized, a combination of three agents producing the maximum effect. (3) The clot grew more quickly than the solid tumor in both the control and the treated groups. There was a high correlation (r = 0.93 in M-5076, and r = 0.64 in MH-134) between the growth rates of ascites and solid tumor in SRCA. (4) Histological examination revealed that viable tumor cells infiltrated widely under the renal capsule in both types of tumors. These results suggest that ascites and solid tumor are useful materials for the subrenal capsule assay method. PMID- 2197357 TI - [Studies on cross correlation coefficient of fetal heart rate and fetal movement signals detected by ultrasonic Doppler fetal actocardiograph]. AB - Cross correlation coefficients of fetal heart rate (FHR) and fetal movement (FM) signals detected by ultrasonic Doppler actocardiograph were studies. Actocardiographic output was stored in a floppy disk through an AD converter. The parameters for every 5 minute period were calculated in 461 periods for 68 normal pregnant women at 14 to 41 weeks of gestation. 1) Between FHR acceleration (ACC) and the maximum coefficient, the averages for the maximum coefficients in 5 minute periods without and with ACC were 0.141 and 0.275, respectively. The respective lag time averages were 13.1 and 7.6 seconds. These results may indicate that the FHR ACC temporarily follow FM with a time lag of several seconds in the active state. 2) The largest value for the maximum coefficients and the lag times in each examination were investigated according for each gestational week. The coefficients increased and the lag times decreased as gestation advanced. 3) The coefficients in the periods showing typical fetal breathing movement and fetal hiccups were very small. Periodic fetal suckling observed with real-time B mode showed large coefficient with a 3 sec' delay in FM. PMID- 2197358 TI - Hematologic evaluation of growth retarded fetus by cordocentesis. AB - Fetal blood sampling by ultrasound-guided cordocentesis was performed in 22 IUGR fetuses in order to evaluate the fetal condition. All patients were referred to our hospital for further examination and management. In addition to hematological assessment we measured the velocity profiles of the umbilical artery with pulse gated Doppler equipment. On the whole, pH and pO2 in the umbilical vein of IUGR fetuses were significantly lower and pCO2 higher, respectively, the corresponding values in controls. In particular, IUGR fetuses which had an etiology of maternal pre-eclampsia had fallen into hypoxemia. However, other laboratory values in IUGR did not differ from those of the controls except for the platelet count, which was low in the IUGR fetuses. Five fetuses with chromosomal abnormalities were found by analyzing the fetal blood. Since there are different etiologies inducing IUGR, fetus and umbilical artery velocimetry is not always predictive of the state of the IUGR fetus, hematological assessment is considered indispensable for further management. PMID- 2197359 TI - [Three cases of malignant lymphoma of the cervix uteri]. PMID- 2197360 TI - Computerized ICU data management: pitfalls and promises. PMID- 2197361 TI - Novel fatty acyl substrates for myristoyl-CoA:protein N-myristoyl-transferase. AB - Myristoyl-CoA:protein N-myristoyltransferase (NMT) catalyzes the covalent attachment of myristic acid to the NH2-terminal Gly residues of a number of viral and cellular proteins. The remarkable specificity of this enzyme for myristoyl CoA observed in vivo appears to arise in large part from a cooperativity between NMT's acylCoA and peptide binding sites: the length of the acylCoA bound to NMT influences the interactions of peptide substrates with NMT. We have previously synthesized analogs of myristic acid with single oxygen or sulfur for methylene substitutions. These heteroatom substitutions produce significant reductions in acyl chain hydrophobicity without accompanying alterations in chain length or stereochemical restrictions. In vitro studies have shown that the CoA thioesters of these analogs are substrates for S. cerevisiae NMT and that the efficiency of their transfer to octapeptide substrates is peptide sequence-dependent. In vivo studies with cultured mammalian cells have confirmed that these fatty acid analogs are selectively incorporated into a subset of cellular N myristoylproteins, that only a subset of analog-substituted proteins undergo redistribution from membrane to cytosolic fractions, and that these analogs can inhibit the replication of human immunodeficiency virus I and Moloney murine leukemia viruses--two retroviruses that depend upon N-myristoylation of their gag polyprotein precursors for assembly. We have now extended our analysis of NMT acylCoA interactions by synthesizing additional analogs of myristic acid and testing them in a coupled in vitro assay system. Myristic acid analogs with two oxygen or two sulfur substitutions have hydrophobicities comparable to that of hexanoic acid and decanoic acid, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2197363 TI - Tissue-specific regulation of prolactin gene expression. AB - The past 2 years have seen dramatic progress in our understanding of the molecular basis of prolactin gene expression in the pituitary gland. The identification of the pituitary-specific factor Pit-1/GHF-1 has been a major advance, and it leads to new questions, such as the basis for the tissue specificity of Pit-1/GHF-1 expression itself. It clearly cannot be the only factor involved, as it is found in three pituitary cell types, yet prolactin is expressed in only one of these. It is probable that a network of trans-acting factors, some tissue-specific and some ubiquitous but hormonally activated, interact to determine the overall pattern of expression of the prolactin gene, and the dissection of this system should provide some valuable insights into endocrine gene regulation in general. PMID- 2197362 TI - Defining the application portfolio for an integrated hospital information system: a tutorial. AB - Although many successful applications in the hospital environment have been introduced and implemented, hospital information systems have had little impact upon the daily operation of hospitals. Furthermore, integrated hospital information systems, although vital to the hospitals' functioning, have proved to be more complicated to develop and difficult to harness than expected. This paper discusses the need for an integrated hospital information system and provides a framework for the development of its application portfolio. The scope of such a system is the integration of the medical, administrative and fiscal information elements of the hospital into a unified systems environment. PMID- 2197365 TI - Intracrine regulation at the nucleus--a further mechanism of growth factor activity? PMID- 2197364 TI - The paracrine role of angiotensin in gonadotrophin-releasing hormone-stimulated prolactin release in rats. AB - It is well known that lactotrophs are in close proximity to gonadotrophs in the lateral region of the pituitary gland, and thus there is interest in interactions between these two types of cell. The present study was undertaken to investigate the role of angiotensin II (AII) in gonadotrophin-releasing hormone (GnRH) induced prolactin release, and to examine the effect of oestradiol on the paracrine interaction among anterior pituitary cells of young male rats. Over a 3 day period, one group of rats was injected twice with polyoestradiol phosphate (0.5 microgram/g body weight; PEP-treated group), and a second with saline (control group). Their anterior pituitary glands were enzymatically dispersed and, subsequently, the cells were allowed to reaggregate for 48 h. A 20-min perifusion with 100 nmol GnRH/l increased (P less than 0.01) prolactin release from these anterior pituitary cell aggregates. The integrated value for prolactin release was 9.1 +/- 2.9 ng/10(7) cells. In the PEP-treated group, basal release of prolactin was greater than that in the control group (P less than 0.01). However, during exposure to GnRH, the integrated amount of prolactin release by the PEP-treated group (12.5 +/- 4.8 ng/10(7) cells) was not significantly different from that of the control group, although in each individual experiment the GnRH-stimulated prolactin release from the PEP-treated cells was higher than that from the cells that had not been exposed to PEP. The release of angiotensin I (AI) from these perifused pituitary aggregates was significantly (P less than 0.01) increased by GnRH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2197366 TI - Regulation of insulin-like growth factor-I gene expression by growth factors in cultured vascular smooth muscle cells. AB - The aim of this investigation was to study the regulation of insulin-like growth factor-I (IGF-I) gene expression in cultured rat aortic smooth muscle cells. Near confluent cells were deprived of serum for 24 h and then exposed to IGF-I, insulin, serum, basic fibroblast growth factor (basic FGF), platelet-derived growth factor (PDGF-BB; consisting of B-chain homodimer) or GH for 24 h. Levels of IGF-I mRNA were measured by solution hybridization. The level of IGF-I mRNA was markedly decreased by 10% (v/v) newborn calf serum (78 +/- 4 (S.E.M.) % decrease), 1 nmol basic FGF/l (53 +/- 8%), and 1 nmol PDGF-BB/l (40 +/- 3%) when measured after 24 h. The effect of PDGF-BB was significant after 6 h and became more marked after 24 h. GH (1 nmol/l or 0.1 mumol/l) or insulin (1 nmol/l) had no effect after 24 h, whereas IGF-I (1 nmol/l) and insulin (10 mumol/l) increased IGF-I mRNA 64 +/- 20% and 46 +/- 14% respectively. The increase caused by IGF-I was demonstrated after 3 h, and was most marked after 24 h. Using Northern blot analysis of cultured aortic smooth muscle cells, IGF-I transcripts of 7.4, 1.7 and 1.1-0.8 kilobases were observed. Exposure of the cells to 10% serum, 1 nmol basic FGF/l or 1 nmol PDGF-BB/l for 48 h increased the cell number by 104 +/- 7%, 64 +/- 3% and 61 +/- 22% respectively, while IGF-I, insulin and GH had little effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2197367 TI - Role of the paraventricular nucleus in controlling the frequency of milk ejection and the facilitatory effect of centrally administered oxytocin in the suckled rat. AB - The milk-ejection reflex was studied in anaesthetized, lactating Wistar rats in order to evaluate the contribution of the paraventricular nucleus (PVN) to the patterning of milk ejection and the facilitatory action of centrally administered oxytocin. In the first series of experiments, radiofrequency lesions were performed and centred: (1) antero-dorsal to the PVN, damaging parts of the medial septum and anterior hypothalamus; (2) in the PVN, such that much of the parvocellular division was destroyed, but parts of the magnocellular division remained intact; or (3) in the PVN, destroying both parvocellular and magnocellular divisions. Suckling tests performed before and after lesioning showed that the milk-ejection interval was significantly increased (decreased frequency) after lesioning in groups 2 and 3, but that milk-ejection amplitude was significantly decreased only in group 3. These results suggest that damage to the parvocellular division of the PVN affects milk-ejection frequency, but that damage to the magnocellular PVN only affects amplitude. Subsequent tests on rats injected into the PVN with the neurotoxin N-methyl-D,L-aspartate revealed a fall in the amplitude and frequency of milk ejection, similar to that after complete radiofrequency lesions of the PVN. In the second series of experiments, the facilitatory action of centrally administered oxytocin (1 mU, 2.2 ng) was examined in animals bearing either sham or complete PVN lesions. In both groups, intracerebroventricular injection of oxytocin was able to increase the frequency of milk ejections, although the incidence of milk ejection was lower in the pre- and post-injection period in the PVN-lesioned animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2197368 TI - Delayed rectifying and calcium-activated K+ channels and their significance for action potential repolarization in mouse pancreatic beta-cells. AB - The contribution of Ca2(+)-activated and delayed rectifying K+ channels to the voltage-dependent outward current involved in spike repolarization in mouse pancreatic beta-cells (Rorsman, P., and G. Trube. 1986. J. Physiol. 374:531-550) was assessed using patch-clamp techniques. A Ca2(+)-dependent component could be identified by its rapid inactivation and sensitivity to the Ca2+ channel blocker Cd2+. This current showed the same voltage dependence as the voltage-activated (Cd2(+)-sensitive) Ca2+ current and contributed 10-20% to the total beta-cell delayed outward current. The single-channel events underlying the Ca2(+) activated component were investigated in cell-attached patches. Increase of [Ca2+]i invariably induced a dramatic increase in the open state probability of a Ca2(+)-activated K+ channel. This channel had a single-channel conductance of 70 pS [( K+]o = 5.6 mM). The Ca2(+)-independent outward current (constituting greater than 80% of the total) reflected the activation of an 8 pS [( K+]o = 5.6 mM; [K+]i = 155 mM) K+ channel. This channel was the only type observed to be associated with action potentials in cell-attached patches. It is suggested that in mouse beta-cells spike repolarization results mainly from the opening of the 8 pS delayed rectifying K+ channel. PMID- 2197369 TI - Analysis of very late gene expression by Autographa californica nuclear polyhedrosis virus and the further development of multiple expression vectors. AB - The consequences of locating the polyhedrin gene coding sequences and the p10 promoter at heterologous positions within the Autographa californica nuclear polyhedrosis virus (AcMNPV) genome were investigated. Positioning the polyhedrin or beta-galactosidase coding sequences under the control of the p10 gene promoter via the use of the new transfer vector, pAcUW1, resulted in viable recombinant viruses able to produce high levels of each non-fused gene product at the appropriate time. Polyhedra were also produced by the virus with the p10 promoter polyhedrin hybrid gene and appeared normal in thin sections. Therefore the combination of polyhedrin promoter and coding sequences is evidently not essential for efficient expression of this protein. The p10 promoter can serve this function equally well. Viruses with the p10 promoter and beta-galactosidase coding sequences placed upstream from the polyhedrin gene in either orientation produced large amounts of beta-galactosidase protein in infected cells, thus demonstrating that the p10 promoter can function at an alternative position within the virus genome. A second transfer vector, pAcUW2B, was constructed, with a copy of the p10 gene promoter placed upstream and in opposition to the polyhedrin gene. This mediates the insertion of any foreign gene under the control of the p10 promoter while preserving normal p10 gene expression. The advantages of these constructs over the conventional vectors presently used to express foreign genes in insect cell systems and their utilization in the production of virus insecticides are discussed. PMID- 2197370 TI - Expression of influenza A and B virus nucleoprotein antigens in baculovirus. AB - Full-length cDNA clones of the nucleoprotein (NP) genes of influenza A/Ann Arbor/6/60 and B/Ann Arbor/1/86 viruses were constructed from virion RNA and subsequently expressed in Spodoptera frugiperda (Sf9) cells using the baculovirus vector, Autographa californica nuclear polyhedrosis virus. Western blot analysis of lysates prepared from Sf9 cells infected with the recombinant viruses confirmed that the baculovirus-expressed NP antigens were reactive with monoclonal antibodies specific for either type A or B NP and with anti-NP antibodies in human serum samples. Electrophoretic analysis indicated that the expressed NP antigens comigrated with NP purified from influenza A or B virions and that the recombinant NP antigens represented greater than 10% of total protein in infected cells. Dilutions of clarified Sf9 cell lysates were used as antigens in a standard enzyme immunoassay to detect serum antibody specific for influenza A or B viruses. The results from assays using the baculovirus-expressed NP antigens showed good correlation with the results obtained using bacterially expressed NP antigen as well as complement fixation. Therefore, baculovirus expressed NP antigens have the potential to be used to develop reproducible and routine assays for the serodiagnosis of influenza virus infections as an alternative to the complement fixation or haemagglutination inhibition tests. PMID- 2197371 TI - Analysis of the local and systemic immune responses induced in BALB/c mice by experimental respiratory syncytial virus infection. AB - Pulmonary A2 strain respiratory syncytial virus infection of BALB/c laboratory mice persisted for up to 7 days after initial infection with peak virus titres being recovered on day 4. Virus antigen within the lungs was found to be restricted essentially to the alveolar regions. Similarly, pulmonary histopathological changes remained confined to the peri-alveolar regions being consistent with mild pneumonia. Infection was found to elicit a pulmonary major histocompatibility complex-restricted cytotoxic T lymphocyte (CTL) response which was first detectable 6 days after infection and optimal 7 to 9 days after infection. This local CTL response was preceded by a rapid transient virus specific lymphocyte transformation response which was detectable only 3 days after intranasal infection. In addition, infection induced rapid interferon production within the lungs which was accompanied by an equally rapid rise in pulmonary natural killer (NK) cell cytotoxic activity. Enhanced NK cell cytotoxicity could be detected after only 1 day post-infection and continued to rise to maximum levels on day 3. This response like the acute CTL response was found to be restricted to the lower respiratory tract. IgG was the first class of virus-specific immunoglobulin to be detected in the lungs of infected animals after experimental infection. However, IgG was not detected until day 10 post infection, 5 days after the initial decline of virus shedding. Virus-specific IgA although detectable did not appear in the lung until day 24. PMID- 2197373 TI - MOPAC: a semiempirical molecular orbital program. PMID- 2197372 TI - Detection of the trans activity of the plum pox virus NIa-like protease in infected plants. AB - The NIa-like protein of plum pox virus is a protease with high sequence specificity that is autocatalytically released from the viral polyprotein. In order to determine whether the protease is active in trans we constructed a fusion protein consisting of the C-terminal region of the plum pox virus polyprotein and the staphylococcal Protein A. The authentic protease recognition sequence Asn-Val-Val-Val-His-Gln-Ala occurs in the centre of this protein fusion. This protein was cleaved specifically by extracts of plum pox virus-infected plants due to the strong activity of the viral protease making it a useful tool for diagnostic purposes. PMID- 2197374 TI - Organization of microtubules in cochlear hair cells. AB - The organization of microtubules in hair cells of the guinea-pig cochlea has been investigated using transmission electron microscopy and correlated with the location of tubulin-associated immunofluorescence in surface preparations of the organ of Corti. Results from both techniques reveal consistent distributions of microtubules in inner and outer hair cells. In the inner hair cells, microtubules are most concentrated in the apex. Reconstruction from serial sections shows three main groups: firstly, in channels through the cuticular plate and in a discontinuous belt around its upper perimeter; secondly, forming a ring inside a rim extending down from the lower perimeter of the plate; and thirdly, in a meshwork underlying the main body of the plate. In the cell body, microtubules line the inner face of the subsurface cistern and extend longitudinally through a tubulo-vesicular track between the apex and base. In outer hair cells, the pattern of microtubules associated with the cuticular plate is similar, although there are fewer present than in inner hair cells. In outer hair cells from the apex of the cochlea, microtubules occur around an infracuticular protrusion of cuticular plate material. In the cell body, many more microtubules occur in the region below the nucleus compared with inner hair cells. The possible functions of microtubules in hair cells are discussed by comparison with those found in other systems. These include morphogenesis and maintenance of cell shape; intracellular transport, e.g., of neurotransmitter vesicles; providing a possible substrate for motility; mechanical support of structures associated with sensory transduction. PMID- 2197375 TI - Institutionalized patients with hip fractures: characteristics associated with returning to community dwelling. AB - The authors sought to identify patient- and nursing home-specific characteristics associated with a return to community living among patients with hip fractures discharged initially to nursing homes. One hundred eighty-nine free-living elderly patients were admitted for hip fractures to a 1,120-bed community hospital during 1984-1986. At hospital discharge, 114 (60%) of these patients were institutionalized. One year later, 49/114 (43%) had returned to the community. Three factors independently correlated with patients' return to community living: being discharged to a nursing home with a large ratio of annual admissions to number of beds (RR = 2.51, 95% CI 1.65, 3.94), achieving any in hospital ambulation (RR = 4.24, 95% CI 1.77, 8.14), and receiving conventional Medicare insurance (RR = 0.37, 95% CI 0.05, 0.53). These data suggest the existence of patient and nursing home features that identify those institutionalized patients with hip fractures who are more likely to return to community dwelling. PMID- 2197376 TI - Cognitive function in hypertensives treated with atenolol or propranolol. AB - STUDY OBJECTIVE: To test reports that beta blockers, particularly lipophilic forms, impair cognitive function and cause psychiatric disturbances. DESIGN: Randomized, double-blind, controlled crossover trial with eight-week treatment periods. PATIENTS: Sequential sample of 42 male veterans, with untreated diastolic blood pressures (DBP) between 90 and 110 mmHg, aged 35-64 years. INTERVENTIONS: Propranolol-LA, 80-mg tablets, or atenolol, 50-mg tablets, were given daily, incremented by one tablet at weekly intervals until DBP less than or equal to 90 mmHg. Hydrochlorothiazide was added, if necessary. MAIN RESULTS: Repeated-measures ANOVA was performed on all cognitive tests. Cognitive test performance was not affected by beta blocker therapy in seven of nine tests and was enhanced on Trail Making Test. Performance was impaired only on Digit Cancellation. Neither Speilberger's State Trait Anxiety Inventory nor the Beck Depression Inventory was affected by either beta blocker. CONCLUSIONS: Atenolol or propranolol therapy does not impair cognitive function or contribute significantly to psychiatric side effects. PMID- 2197377 TI - An evaluation of residency training in interviewing skills and the psychosocial domain of medical practice. AB - Competent use of interviewing skills is important for the care of all patients but is especially critical, and frequently deficient, in meeting the needs of patients experiencing emotional distress. This study presents an evaluation of a curriculum in communication and psychosocial skills taught to first-year medical residents. A randomized experimental design compared trained and untrained residents' (n = 48) performances with a simulated patient presenting with atypical chest pain and psychosocial distress. Evaluation was based on analysis of videotapes, simulated patient report of residents' behaviors, and chart notation. Trained compared with untrained residents asked more open-ended questions and fewer leading questions, summarized main points more frequently, did more psychosocial counseling, and were rated as having better communication skills by the simulated patient. The use of more focused and psychosocially directed questions, and fewer leading and grab-bag questions, was associated with more accurate diagnoses and management recorded in the medical chart. However, no significant difference was found in the charting practices of trained versus untrained residents. PMID- 2197379 TI - Leaders in medicine: Jess D. Herrmann, MD. PMID- 2197380 TI - A.B.Cs periodontics. "N" is for Nonsurgical treatment. PMID- 2197381 TI - Double-blind comparison of meclofenamate sodium plus codeine, meclofenamate sodium, codeine, and placebo for relief of pain following surgical removal of third molars. AB - A single-dose, randomized, double-blind, parallel-treatment study was performed in 200 outpatients with acute pain caused by the surgical removal of impacted third molars. Meclofenamate 100 mg plus codeine 60 mg, meclofenamate 50 mg plus codeine 30 mg, meclofenamate 100 mg, codeine 60 mg, and placebo treatment groups were compared for sum of pain intensity differences, peak pain intensity difference, sum of pain relief scores, peak pain relief, number of observations at which pain was half relieved, overall evaluation of effectiveness, and time to remedication with a backup analgesic. Meclofenamate 100 mg plus codeine 60 mg was significantly more effective (P less than .005) than codeine 60 mg for all variables except number of observations at which pain was half relieved. Both meclofenamate-codeine combinations and meclofenamate 100 mg alone were significantly more effective (P less than .005) than placebo for all variables. Eleven adverse experiences were reported in 7 patients (3.5%); the most common was somnolence in 1 patient receiving meclofenamate 100 mg plus codeine 60 mg, in 2 treated with meclofenamate 50 mg plus codeine 30 mg, and in 1 treated with codeine 60 mg. PMID- 2197378 TI - Detecting acute cardiac ischemia in the emergency department: a review of the literature. PMID- 2197382 TI - Preanesthetic medication with rectal midazolam in children undergoing dental extractions. AB - Three different dosages (0.25, 0.35, and 0.45 mg/kg) of rectally administered midazolam were compared with each other and with placebo for preanesthetic medication in children undergoing dental extractions. Eighty patients between the ages of 2 and 10 years were randomly allocated into four groups in this double blind study. The results from this trial show that 30 minutes after rectal administration of all doses of midazolam, good anxiolysis, sedation, and cooperation were obtained in most patients. A high prevalence (23%) of disinhibition reactions was observed, particularly in the 0.45 mg/kg group. For this reason, 0.25 or 0.35 mg/kg appears to be the dose of choice when rectal midazolam is used for premedication in children. PMID- 2197383 TI - Foreign body giant cell reaction related to placement of tetracycline-treated polylactic acid: report of 18 cases. AB - Presented are 18 cases of foreign body giant cell reaction in mandibular third molar extraction wounds previously treated with 40 mg of dry tetracycline powder carried into the wound with a biodegradable polymer dressing. The lesions vary in intensity from local, soft tissue granulomas to osteolytic, central bone pathologies. Several reports of foreign body giant cell reaction to insoluble tetracycline preparations are cited, along with a brief review of the relationship between myospherulosis and various formulations of tetracycline powder in petroleum-based carrier vehicles. The authors suggest that the foreign body giant cell lesions reported here were initiated by micron-sized particles of insoluble tetracycline powder and were further aggravated by certain hydrophobic characteristics of the associated biodegradeable polymer. The authors caution against use of dry, powdered forms of topical antibiotics in fresh dental extraction wounds. PMID- 2197384 TI - Cutaneous approaches to the orbital skeleton and periorbital structures. AB - Multiple cutaneous approaches to both the superior and inferior orbit have been reviewed. Incisional choices are optimally based on both facial esthetics and orbital function, which are achieved by an understanding of the unique anatomy of this region. The superior orbit is best approached by a blepharoplasty (lid crease) incision in conjunction with a lateral extension if additional exposure is necessary. Almost all aspects of the bony orbit can be reached with the exception of the frontal bone superior to the supraorbital rim. When wide exposure of the orbital skeleton is necessary, a bicoronal scalp flap is most effective in a nonalopecic patient. The inferior orbit can be approached by a ciliary, blepharoplasty, or conjunctival incision with a lateral canthotomy. None has proven esthetic advantages over the others, with the exception of the conjunctival incision when used alone. The lid incisions must be used with the understanding that orbital function must be assessed both pre- and postoperatively and meticulous attention paid to protection and care of the anterior globe. In addition, because of the thinness of the tissues being manipulated, edema, bruising, and final settling of lid form may require more postoperative time than is typical of more peripheral approaches. PMID- 2197385 TI - Central mucoepidermoid carcinoma of the jaws: report of four cases with analysis of the literature and discussion of the relationship to mucoepidermoid, sialodontogenic, and glandular odontogenic cysts. PMID- 2197386 TI - Hemangioma and malignant hemangioendothelioma of the maxillary sinus: case reports and clinical consideration. PMID- 2197387 TI - The use of perimandibular sutures in isolated vestibuloplasty or floor of the mouth plasty procedures. PMID- 2197388 TI - Relapse to substance abuse: empirical findings within a cognitive-social learning approach. AB - A cognitive-social learning model of relapse prevention, specifically Albert Bandura's theory of self-efficacy, is one of the most influential theoretical frameworks that has been applied to the problem of relapse in the substance abuse field. Theory and related empirical findings within this approach are reviewed, including the following: the assessment of a client's high-risk situations for relapse; the development of an individualized treatment plan; the distinction between treatment strategies aimed at "initiation" versus "maintenance" of behavior change; the importance of growth in client self-efficacy; the difference between the process of lapse versus relapse; the use of drugs in relapse prevention counseling; and the role of client-treatment matching. On the basis of the empirical evidence reviewed, it is concluded that a cognitive-social learning approach to relapse prevention is showing promise. Future directions for research are suggested. PMID- 2197389 TI - The Cenaps model of relapse prevention: basic principles and procedures. AB - Nine basic principles that underlie the Cenaps relapse prevention planning process are described. Each principle is complemented with a procedure or clinical technique that can be used to operationalize that principle with patients: the first principle of self-regulation is operationalized with a procedure for physical, psychological, and social stabilization; the second principle of integration is operationalized by the technique of self-assessment; the third principle of understanding is operationalized by a relapse education procedure; the fourth principle of self-knowledge is operationalized with a procedure of relapse warning-sign identification; the fifth principle of coping skills is operationalized through a procedure of warning-sign management; the sixth principle of change is operationalized in a procedure for reviewing the recovery plan; the seventh principle of awareness is operationalized by a procedure of inventory training; the eighth principle of support is operationalized by the involvement of significant others; and the ninth principle is maintenance, which is operationalized by a comprehensive follow-up plan. PMID- 2197390 TI - Abstinence and relapse in outpatient cocaine addicts. AB - A discussion is provided of clinical techniques for establishing abstinence and preventing relapse in cocaine addicts within the context of an intensive outpatient treatment program. A basic tenet of this article is that to produce higher success rates in these and other drug-dependent patients more attention must be paid to some very fundamental treatment issues, such as program structure, counselor attitude, and patient motivation. PMID- 2197391 TI - Treating crack cocaine dependence: the critical role of relapse prevention. AB - In order to adequately address the treatment needs of crack cocaine dependent persons, a multidimensional approach to relapse prevention must be utilized. The value of a biopsychosocial model of crack addiction and the concept of phases of recovery in providing a rationale for the recommended approach to relapse prevention are emphasized. Research findings on the determinants of relapse for crack dependent patients and the psychosocial characteristics of the crack dependent individual justify the utility of certain relapse prevention strategies. Specifically, an approach to relapse is advocated that includes the provision of pharmacological adjuncts, psychoeducation on the multideterminants of relapse, and psychotherapy that attempts to remediate underlying psychological problems that are typically found in crack dependent patients. PMID- 2197392 TI - Neurobehavioral treatment for cocaine dependency. AB - Relapse prevention techniques have recently been incorporated into some nonpharmacologic models of chemical dependency treatment. The neurobehavioral model of cocaine dependency treatment establishes a clear timetable for recovery from cocaine dependency and focuses on four distinct areas of functioning. Strategies for addressing these areas of functioning include the use of relapse prevention methods and individual therapy procedures, family systems materials, 12-Step involvement, and urine testing. The model constructs a comprehensive framework for facilitating involvement in recovery activities that promote positive behavior change. The relapse prevention group component of the model is described, the use of a systematic relapse analysis procedure is presented, and an outline of plans for evaluating the model is discussed. The development of a comprehensive outpatient treatment model for treating cocaine dependency provides a standardized structure within which other treatment interventions (e.g., medication, acupuncture) could be evaluated. PMID- 2197393 TI - Applications of relapse prevention with moderation goals. AB - A brief description of the controversy surrounding moderation goals for individuals with alcohol problems is provided. Although the controversy is as yet unresolved, particularly for severely dependent individuals, evidence for the utility and appropriateness of offering goal choices (including moderation goals) to less dependent problem drinkers is discussed. In addition, secondary prevention of alcohol problems with high-risk drinkers often utilizes moderation goals; these individuals are unlikely to fit the traditional alcoholic pattern, but are at risk for a variety of intoxication-related problems. Relapse prevention, an example of a tertiary prevention program to facilitate abstinence in the treatment of addiction, may also be applied to secondary prevention (moderation) goals. Following a description of the relapse prevention approach and its use with moderation goals, two studies applying this approach to secondary prevention are discussed, and summaries of the results are presented. PMID- 2197394 TI - A randomized controlled trial of recovery training and self-help for opioid addicts in New England and Hong Kong. AB - The efficacy of a group relapse prevention program, Recovery Training and Self help (RTSH), was investigated experimentally with opioid addicts in New England and Hong Kong. The experimental program featured weekly attendance at a professionally led recovery-training session, a peer-led self-help style meeting and a weekend recreational activity. Researchers randomly assigned newly recovering opioid addicts (N = 168) to experimental and control conditions, and followed them to assess their outcomes; 98% provided follow-up data. The intervention significantly reduced the probability and extent of relapse and helped unemployed subjects find work. RTSH also significantly reduced self reported criminality. These findings suggest that relapse prevention programs can be effective in helping opioid addicts achieve long-term recovery. PMID- 2197395 TI - Preventing relapse in the treatment of nicotine addiction: current issues and future directions. AB - Although smoking-cessation rates have continued to increase, the vast majority of smokers who quit eventually relapse. Between 1974 and 1985, over 1.3 million smokers quit during each of those years. However, 75% to 80% of those individuals resumed smoking within six months. This article describes the dynamic phenomenon of smoking relapse within the context of cyclical episodes of smoking and quitting during an individual's lifetime. Theories of the determinants of smoking relapse are reviewed and methods designed to prevent relapse are described. Smoking relapse is discussed in terms of three aspects of tobacco addiction: (1) biological-addiction mechanisms, (2) conditioning processes, and (3) cognitive social learning factors. The major determinants of smoking relapse are reviewed, including nicotine withdrawal, stress, weight gain, social influences, conditioning factors, causal attributions, and environmental variables. A trans theoretical-developmental model is explored in the longitudinal investigation of the natural history of slips (lapses) and relapse episodes. Relapse prevention interventions are described that emphasize self-awareness, self-regulation, self efficacy, affect regulation, social support, and lifestyle balance. Recent developments in pharmacological adjuncts to treatment are also examined. It is concluded that innovative relapse prevention methods need to be designed for hard core smokers with histories of cessation failures, substance abuse and/or psychiatric impairment. These and other recommendations for future research on smoking relapse and relapse prevention are discussed. PMID- 2197396 TI - The role of incest issues in relapse. AB - Comprehensive studies have established that relapse is the most common outcome of recovery programs treating addictive behaviors. This article examines the fact that relapse is often related to uncovering painful early childhood incest experiences that have been defended against through self-destructive addictive behaviors. Another aspect of relapse is the phenomenon of multiaddictions: withdrawal from an identified addictive behavior will often lead to the unmasking of other addictive behaviors. The phenomenon of cross-addiction is widely acknowledged in the addictions field, but the connection between cross-addiction and relapse needs to be more fully explored. This article focuses on the following points: (1) addictive behaviors may serve to defend against memories of sexual abuse; (2) unidentified incest material may precipitate relapse or result from relapse, and therefore must be considered as a possible component of treatment in recovery--indications for treatment in terms of 12-Step recovery in conjunction with therapy are explored; (3) relapse may indicate the existence of additional addictions that must be identified and explored in order for recovery to proceed; and (4) sex and love addiction is often found in conjunction with alcoholism, codependency and compulsive overeating, and often comes to light through the emergence of incest memories. The identification and treatment of this hidden addiction (i.e., sex and love addiction) will determine the extent and depth of recovery. PMID- 2197397 TI - Sampling issues in research with nonorganic failure-to-thrive children. AB - Describes the methodological problems posed by sampling characteristics of nonorganic failure-to-thrive (NOFT) children and strategies to address them. Sources of variance in sample characteristics include the criteria used to define NOFT, populations from which samples are drawn, parent refusal and sample attrition, medical and psychological treatment, and individual differences in environmental or biologic risk factors. Undesirable consequences of unrecognized intrasample variation in NOFT include sample bias, limited generalizability of findings across different settings, and erroneous assumption of sample homogeneity. Comprehensive description of sample selection and characteristics will enhance more accurate definition of NOFT, generalizability of findings, and evaluation of the impact of sampling characteristics. Future studies should focus on objective assessment of subtypes of NOFT and the relationship of individual difference variables to psychological status and prognosis. PMID- 2197398 TI - Toothgate scandal: how Florida's department of health and rehabilitative services have operated the Medicaid dental program (EPSDT) illegally. PMID- 2197399 TI - Effects of cleaning, polishing pretreatments and acid etching times on unground primary enamel. AB - The purpose of this study was to investigate the influence of cleaning and polishing pretreatments and etching times on unground primary enamel smooth surfaces with respect to the quality of etching patterns. Labial surfaces of 117 extracted or exfoliated caries free primary anterior teeth were used. Various cleaning and polishing methods were used before etching. Etching times with 40% phosphoric acid gel were 10, 30 and 60 seconds and all specimens were washed with an air water spray for 30 seconds. The following observations were obtained using the SEM. 1. There was not a significant difference between the appearance of prism structures by etching and the pretreatment methods in the 60 and 30 seconds etching. 2. The shorter the etching time, the higher was the rate of the cases which did not show any prism structure after etching. PMID- 2197400 TI - Estimation of sensitivity and specificity of site-specific diagnostic tests. AB - Clinical trials designed to estimate the sensitivity and specificity of periodontal diagnostic tests often use multiple sites per patient as experimental units of analyses. Since site-specific test results within a patient are dependent observations, a correlated binomial model should be employed to estimate the sensitivity and specificity of these diagnostic tests. Ignoring the within-patient correlation can result in an over- or underestimation of the true standard errors. PMID- 2197401 TI - [Intracellular calcium ion mobilization and nicotinic acetylcholine receptor mediated signal transduction in neuro-skeletal muscle synapse]. AB - Intracellular Ca2+ mobilization in neuro-skeletal muscle synapse was studied by measuring Ca2(+)-aequorin luminescence transients (Ca2+ transients). Ca2+ transients were categorized into three groups as follows: (1) The 1st phase of rapid Ca2+ mobilization was accompanied with twitch tension, (2) the 2nd phase of slow Ca2+ mobilization was not accompanied with twitch tension, and only observed in the presence of cholinesterase inhibitors, and (3) the 3rd phase was spontaneous Ca2+ mobilization which was rather related to contracture. The caffeine effects were composed of 1st phase-potentiation (cyclic AMP increase?), 2nd phase-inhibition (n-acetylcholine receptor (AChR) closely related), and the increase of 3rd phase (Ca2+ release from salcoplasmic reticulum). d-Tubocurarine showed much higher potency for the inhibition of the 2nd phase than for that of the 1st phase. These results suggest that the 1st phase Ca2+ transients are related to T-type n-AChR channel, whereas the 2nd phase Ca2+ transients are related to S-type n-AChR channel and its mediated signal transduction. PMID- 2197402 TI - Development and application of antibiotic-loaded bone cement beads. AB - The authors presented an overview of the development of antibiotic-loaded bone cement beads and their indications for usage, method of application, advantages, disadvantages, and causes of failure. This method of treatment for bone and soft tissue infections of the foot is not a panacea and should be used only in selected cases. The vascular status and the physiologic ability of the patient to heal a peripheral wound or infection are the basis for the success of this method of therapy. European literature makes little mention of adjunctive systemic antibiotic therapy with local antibiotic-loaded bone cement bead use. It is the authors' opinion that clinical judgment should be used to determine the necessity for such therapy. PMID- 2197403 TI - Foot deformity of unknown etiology in a prehistoric skeleton from Texas. AB - An unusual foot deformity in an archaeological specimen from Oldham County, Texas, is presented. It is hoped that through description and radiographic and photographic examination the readers will be able to offer opinions concerning the frequency or possible etiology of the condition. PMID- 2197404 TI - Chirurgeon: look to the wounded. PMID- 2197405 TI - Space motion sickness. AB - Space Motion Sickness (SMS) is the malady which frequently occurs shortly after attainment of sustained exposure to hypogravity. It is characterised by a variety of symptoms, which may proceed to nausea and eventually vomiting. Natural adaptation usually occurs if exposure to hypogravity is maintained. The condition appears to be the manifestation of motion sickness that is specific to hypogravity. It is associated with otolith-canal and otolith-eye conflict. SMS may have operational significance in impairing the performance of spacecraft crews. The condition is likely to be amenable to treatment with anti-motion sickness drugs. It may be possible to reduce any operational effects of SMS by suitable crew selection and training procedures. PMID- 2197406 TI - The diary of assistant surgeon Henry Piers, HMS Investigator, 1850-54. AB - From the 16th to the mid 19th century, many voyages were made from England to discover a North West Passage between the Atlantic and the Pacific oceans. The Investigator was one of some 40 vessels that searched for the lost North West Passage expedition of 1845-48 under the command of Sir John Franklin in HM Ships Erebus and Terror, which became beset among what are now known as the Canadian Arctic Islands. The "Investigators" found no trace of Franklin, but were the first to traverse the North West Passage, although their ship had to be abandoned in Mercy Bay on Banks Island after two winters there. The diary of Assistant Surgeon Henry Piers, from the manuscript collection of the National Maritime Museum, Greenwich, is here examined. Reference is also made to the narrative and report published by the senior surgeon of the Investigator, Dr Alexander Armstrong. PMID- 2197407 TI - The Journal of the Royal Naval Medical Service: seventy-five years on. PMID- 2197408 TI - Sickle cell trait and military service. AB - In the community great efforts have been made to educate those with sickle cell trait that their condition is not a handicap and that they are fit to lead a normal life. It would be seen as a retrograde step for the Armed Forces to imply that they are in some way unfit for normal duties. The evidence presented demonstrates that with the exception of a small excess risk of sudden unexplained death during training there is no objection to recruiting those with sickle cell trait into the Royal Navy. At present those with sickle cell disorders are barred from service in the Royal Marine Commandos and from diving, submarine and aircrew service. On the basis of the evidence presented in this review a case can be made for allowing those with sickle cell trait to enter as aircrew in helicopters but not as pilots. In view of the requirements for military divers to operate in cold water under stressful conditions the exclusion of those with sickle cell trait is entirely justified. The overriding requirement must be the safety of both the affected individual and of others and the current regulations reflect this. Screening of all recruits and officer entrants in appropriate racial groups is not performed at present but would allow counselling and advice to be given to those affected by sickle cell trait at an early stage of their careers and the reasons for their exclusion from certain branches fully explained either by establishment Medical Officers or by the haematologist.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2197409 TI - Characterization of a decapacitation factor associated with epididymal mouse spermatozoa. AB - Earlier studies demonstrated that epididymal mouse spermatozoa have a surface associated factor which inhibits fertilizing ability in a reversible manner. The factor can be removed from uncapacitated spermatozoa by gentle centrifugation, resulting in immediately highly fertile gametes, and it can be added back to capacitated spermatozoa, resulting in poorly fertile cells in which the acrosome reaction has been blocked. Using such inhibition of in-vitro fertilizing ability as an assay, we have carried out experiments to characterize the factor. It appears to be an anionic polypeptide with Mr of approximately 40,000 (according to its behaviour on gel filtration). It is stable to heating at 100 degrees C for 15 min and is not destroyed by proteases at pH 8.0, yet inhibitory activity decreases during sperm incubation in capacitating conditions and is also destroyed in partially purified preparations by endogenous enzyme action during incubation at pH 5.0. Activity is not adsorbed to either concanavalin A-agarose or wheat-germ agglutinin-agarose, suggesting that terminal mannose and N acetylglucosamine residues are not abundant. The factor causes rapid changes in the patterns of chlortetracycline fluorescence seen on sperm heads, a parameter used to assess the capacitated state. Removal of the factor from uncapacitated cells results in a shift to a predominance of capacitated patterns, while the addition of crude or partially purified factor to capacitated cells inhibits the acrosome reaction and causes a shift to the uncapacitated pattern in acrosome intact spermatozoa. The factor therefore behaves as a decapacitation factor. However, it appears to differ from other characterized decapacitation factors in terms both of molecular size and of abundance of mannose and N-acetylglucosamine residues. PMID- 2197410 TI - LH responses of female naked mole-rats, Heterocephalus glaber, to single and multiple doses of exogenous GnRH. AB - To investigate possible differential pituitary secretion of LH in breeding and non-breeding female naked mole-rats, the LH responses to administration of exogenous GnRH were measured in 55 females from 20 captive colonies. Single doses of 0.1, 0.5 or 1.0 micrograms GnRH produced a significant rise in plasma LH concentrations 20 min after s.c. injection in breeding and non-breeding females at all doses (P less than 0.001). While at the highest dose of 1.0 microgram there was no difference in the LH response between breeding and non-breeding females, as the dose was lowered there was a progressive decline in the LH response in non-breeding females such that, at the 0.1 microgram dose, GnRH produced only a small, but significant, increase in plasma LH (1.3 +/- 0.2 to 2.9 +/- 0.5 mi.u./ml, N = 5) compared with breeding females (3.4 +/- 0.8 to 9.6 +/- 2.0 mi.u./ml, N = 6). The LH responses of the latter were not significantly reduced at the lower doses of GnRH. The apparent lack of sensitivity to low doses of exogenous GnRH in non-breeding females was reversed by 4 consecutive 1-h injections of 0.1 microgram, which produced a rise in LH from 1.2 +/- 0.2 to 9.0 +/- 0.2 mi.u./ml (N = 4), comparable to that of breeding females given a single injection of 0.1 microgram GnRH. These results suggest that the anterior pituitary in non-breeding female naked mole-rats is less sensitive to low doses of exogenous GnRH than in breeding females, possibly due to a lack of priming by endogenous GnRH. Therefore, the socially-induced block to ovulation in non breeding female naked mole-rats may be due to inhibition of hypothalamic GnRH secretion. PMID- 2197411 TI - Thermodynamics of the interaction of inhibitors with the binding site of recombinant human renin. AB - The independent subsite model is widely used for the design of peptide inhibitors of enzymes with extended active sites. This model assumes that the subsites are independent of each other and that the free energies of binding contributed by the several subsites are additive. We questioned the strict application of this model for structure-activity studies, since one can, a priori, conceive of likely deviations from this model. Accordingly, we tested the independent subsite model by measuring the thermodynamic binding parameters of a series of peptide inhibitors of human renin. This enzyme-inhibitor system was chosen as a model by virtue of the high degree of specificity of renin for its natural substrate, angiotensinogen, and the availability of a large number of structurally similar peptide inhibitors. Although we found the general mode of binding of these renin inhibitors to be primarily hydrophobic, serious deviations from additivity and independent subsite model constraints were observed. We conclude that an important determinant of binding is most probably the conformation assumed by the peptide inhibitor in solution. Thus, we suggest that caution be exercised in using affinity constants to assess the interactions of peptide inhibitors with human renin and possibly with other enzymes having extended binding sites. Furthermore, the thermodynamic parameters of a class of compounds provide more information as to the mode of binding of ligands to their respective receptors than do dissociation constants. PMID- 2197412 TI - 2-(4-Amino-4-carboxybutyl)aziridine-2-carboxylic acid. A potent irreversible inhibitor of diaminopimelic acid epimerase. Spontaneous formation from alpha (halomethyl)diaminopimelic acids. AB - 2-(4-Amino-4-carboxybutyl)aziridine-2-carboxylic acid (3) (aziridino-DAP) was identified as the product of spontaneous hydrolysis of alpha (halomethyl)diaminopimelic acids (alpha-halomethyl-DAPs) 2a-c. Under physiological conditions, 3 is an extremely potent irreversible inhibitor of the bacterial enzyme diaminopimelic acid epimerase (DAP-epimerase; EC 5.1.1.7). This unusual mode of action of an alpha-halomethyl amino acid with a non-pyridoxal enzyme is investigated. Synthesis and characterization of 2a-c and 3, kinetics of spontaneous formation of 3 from alpha-halomethyl-DAPs, and kinetics of enzyme inhibition by both 3 and by alpha-halomethyl-DAPs are reported. PMID- 2197413 TI - Potent renin inhibitory peptides containing hydrophilic end groups. AB - A previously reported renin inhibitor, Boc-Pro-Phe-N(Me)His-Leu psi [CHOHCH2]Val Ile-Amp (U-71038), was altered by the incorporation of polar, hydrophilic moieties at either end, e.g., tris(hydroxymethyl)aminomethane (THAM) or glucosamine urea groups at the N-terminus, and the THAM amide or aminomethylpyridine N-oxide at the C-terminus. These modified analogues, with dramatically improved water solubility, all retained the potent renin inhibitory activity of U-71038 in vitro. The fact that good activity was maintained in these new analogues, which possess hydrophilicity and steric bulk considerably different from the parent compound, suggests that neither end of these molecules is critical for recognition and binding of the inhibitors by renin. These modified analogues were evaluated in a rat model, and several exhibited hypotensive activity after both oral and iv administration which was greater in magnitude and longer in duration than that caused by equimolar doses of U-71038. Furthermore, unlike U-71038, the oral activity of these analogues was not dependent upon administration in a citric acid vehicle. PMID- 2197414 TI - N-terminal amino-acid sequence and subunit structure of the type IV trimethoprim resistant plasmid-encoded dihydrofolate reductase. AB - The type IV plasmid-mediated dihydrofolate reductase (DHFR), from a clinical strain of Escherichia coli isolated in South India, was prepared from a transconjugant containing the original clinical plasmid, E. coli J62-2 (pUK1123), and from E. coli C600 (pUK1150) containing a 2.6-kb HindIII fragment of pUK1123 cloned into plasmid pBR322. Both preparations were purified by methotrexate affinity chromatography. Automatic amino-acid sequencing of the N-terminal of the purified type IV enzyme from both sources gave an identical sequence which was clearly distinct from other plasmid-mediated trimethoprim-resistant DHFRs. The type IV DHFR showed most homology with the endogenous, chromosomally-encoded E. coli enzyme. Amino-acid sequence analysis also showed that the type IV enzyme preparation from E. coli J62-2 harbouring the original clinical plasmid, pUK1123, also contained the E. coli DNA-binding protein NS1. Analysis by polyacrylamide gel electrophoresis suggested that the type IV enzyme, in its native form, consists of a DHFR of Mr 33,000 coupled to a DNA-binding protein. PMID- 2197416 TI - Confusion and the patient on an intensive topical ocular antibiotic regimen: a case analysis. AB - Round-the-clock instillation of antibiotics disrupts the sleep-wake cycle and may concomitantly result in an acute confusional state. Behavioral manifestations can be attributed to alterations in the sleep-wake cycle; sensory/environmental deficit related to hospitalization; alterations in nutrition and electrolyte balance; age; and medication. Patients at high risk for confusion must be identified and given priority attention. Acute confusion, if not detected and addressed early, may have serious consequences as threatening as the loss of sight. PMID- 2197417 TI - The history of lens implantation in Canada. AB - The first successful intraocular lens implantation in a patient after cataract removal was performed in 1949 by Dr Harold Ridley. Although several ophthalmologists attempted lens implantation with the Ridley implant in the years that followed, the success rate was so poor and the results so inconsistent that the procedure was abandoned until the Binkhorst system was introduced by Dr Kwitko (1966). Lens implantation gained a certain measure of acceptance by 1975; however, major problems still existed, for example, a lack of satisfactory magnification and frequently occurring flat chambers. These problems were solved largely by the introduction of the co-axial microscope and viscoelastic material. PMID- 2197415 TI - The signal peptide. PMID- 2197418 TI - Medicare to help pay for cervical cancer screening every 3 years. PMID- 2197419 TI - Prediction of fatty liver from serum triglyceride levels and body weight indexes. AB - Fatty liver is a common disease in Taiwan. In this study, we tried to evaluate the validity of predicting the presence of fatty liver from clinical data instead of liver biopsy or sonography. From a community survey in Putai, a total of 873 adults older than 30 years and quantified as to triglyceride level, body height, body weight, and the results of the oral glucose tolerance test and upper abdominal sonography were recruited for analysis. Using a receiver operating characteristic (ROC) curve, the best 'cutoff values' for determination of fatty liver were predicted from body weight index and serum triglyceride level in 8 clusters grouped by sex, age and presence or absence of diabetes mellitus. The best cutoff values of triglyceride in the 8 clusters varied from 100 to 170 mg/dl with worse validity. Most of the values were 130 and 140 mg/dl. The cutoff values of body weight index were constant in all clusters and showed greater validity than those for triglyceride. They were 115% or 120%. Their accuracy for the prediction of fatty liver was positively correlated with its prevalence. However, their accuracy was lower than 70% in non-diabetic females. We conclude that body weight index is a good parameter for prediction of fatty liver especially in the high risk groups and we recommend that health-determining cutoff values of serum triglyceride and body weight index should be set at 130 mg/dl and 115%, respectively. PMID- 2197420 TI - Ultrasound of the septum pellucidum. Recognition of evolving fenestrations in the hydrocephalic infant. AB - Fenestrations of the septum pellucidum may be noted in hydrocephalic infants. This finding and its changing image was noted in six premature infants evaluated by neurosonography over time periods ranging from weeks to months. Breaks in the septum were noted to occur from 14 days to 23 weeks after the sonographic diagnosis of hydrocephalus. Some of these fenestrations were noted to increase in size and/or become bilateral over time. The awareness of evolving fenestrations and their late-stage images helps avoid confusion with partial and complete agenesis of the septum pellucidum and their possible associated neuroanatomical abnormalities. PMID- 2197421 TI - Ultrasonography in amebic colitis. AB - Ultrasonography was performed on eight patients with confirmed amebic colitis to determine whether it is possible to differentiate amebic colitis from Crohn's disease or ulcerative colitis. Bowel wall thickening was similar to that found in Crohn's disease and ulcerative colitis; thus, other tests should be used to confirm sonographic findings. However, ultrasonographic findings of thickened bowel wall should suggest amebic colitis in areas endemic for amebiasis. PMID- 2197422 TI - Side-to-side differences and day-to-day variations of transcranial Doppler parameters in normal subjects. AB - We investigated 35 normal adults to assess variations in cerebral artery blood velocities, hemispheric blood velocity ratios, and pulsatility indices, both with regard to changes between the sides and between days. We found no significant variations between sides or days. Changes from one day to the next exceeding 20% in blood velocity in the middle cerebral artery (VMCA), the anterior cerebral artery (VACA), the distal extracranial internal carotid artery (VICA), and in the hemispheric VMCA/VICA, VACA/VICA, or VACA/VMCA ratios, may be considered significant at the 95% level. PMID- 2197423 TI - Intraluminal colonic calcifications associated with anorectal atresia. Prenatal sonographic detection. PMID- 2197424 TI - Serial renal sonographic changes in preeclampsia. PMID- 2197425 TI - An angiomyxoma involving the whole length of the umbilical cord. Prenatal diagnosis by ultrasonography. PMID- 2197426 TI - Ultrasound diagnosis of recurrent intussusception due to inflammatory fibroid polyp of the ileum. PMID- 2197427 TI - Amphotericin B in urological practice. PMID- 2197428 TI - Recurrent superficial transitional cell carcinoma of the bladder: adjuvant topical chemotherapy versus immunotherapy. A prospective randomized trial. AB - A multicenter, prospective, randomized controlled study was begun in 1985 on the effect of ethoglucid and keyhole-limpet hemocyanin in the prevention of recurrent superficial transitional cell carcinoma of the bladder (stages pTa to pT1, grades 1 to 3 according to the recommendation of the International Union Against Cancer and the World Health Organization). The study was performed on a selected group of patients at high risk for further recurrences. All of these patients were pre treated with different chemotherapeutic agents (doxorubicin or mitomycin C) and still had recurrent superficial transitional cell carcinoma. All tumors were removed by transurethral resection and all patients were presumed to be free of tumor at initiation of the prophylactic instillations. Patients in the ethoglucid group received 0.565 gm. (solution of 1%) ethoglucid weekly for 6 weeks and then monthly for 1 year. Patients in the keyhole-limpet hemocyanin group were immunized with 1 mg. keyhole-limpet hemocyanin intracutaneously, and then weekly bladder instillations of 30 mg. were given for 6 weeks and then monthly for 1 year. The percentage of recurrences, recurrence rate, interval free of disease, tumor progression and effect on downstaging were evaluated for both therapeutic arms. The percentage of recurrences (60.9% in the ethoglucid group versus 55.3% in the keyhole-limpet hemocyanin group) and the comparison of interval to recurrence for all patients showed no statistical significant difference (p = 0.808, Mantel-Cox test). A comparison of the interval to recurrence in patients with recurrent tumors only showed a mean interval free of disease of 8.8 months for patients given ethoglucid versus 5.5 months for those given keyhole-limpet hemocyanin (p = 0.006, Wilcoxon test). Recurrence rate (4.8 versus 6.5, respectively) and tumor progression rate (21.7 versus 21.1%, respectively) showed no statistically significant difference (p greater than 0.1). PMID- 2197429 TI - The loop-loosening procedure for urination difficulties after Stamey suspension of the vesical neck. AB - A main complication of an anti-stress urinary incontinence operation in women is postoperative urinary retention or difficulty in urination caused by the urethrovesical junction being suspended too tightly. A total of 7 women who complained of the complication after a modified Stamey operation underwent our procedure in which the suspension loops were loosened to an adequate tension with the patient under local anesthesia. All patients recovered normal voiding without incontinence immediately after the procedure. The Stamey operation uses a nylon loop for suspension of the urethrovesical junction. Therefore, the tightness of the suspension loop can easily be readjusted postoperatively by the procedure, even though initially the suspension of the urethrovesical junction was too tight or too loose. We believe the procedure will enhance the value of the Stamey operation. PMID- 2197430 TI - Cystic dilatations within the pelvis in patients with ipsilateral renal agenesis or dysplasia. AB - A total of 13 cases of cystic dilatations in the pelvis with ipsilateral renal agenesis or dysplasia was detected during renal ultrasonic mass screenings among 280,000 children within the last 2.5 years. The frequency was approximately 0.00464%. These anomalies included 7 cases of Gartner's cyst and 6 of seminal vesicle cyst. Sonographically, the cystic dilatations displayed a typically cystic nature with no internal echoes. The cysts were located laterally or posteriorly to the bladder, and the cystic mass protruded into or was behind the bladder and sometimes bulged the bladder wall. The dysplastic kidney in the patients with ipsilateral cystic dilatations was not detected by sonography due to its small size and the fact that it was obscured by bowel gas or overlying tissue densities. Three cases of dilated ureter communicating with the cyst were found on sonography. Since ultrasonic examination is an excellent method to identify a fluid-filled cystic structure, ultrasonography has become an important modality in the early detection, diagnosis and followup of these cystic dilatations. PMID- 2197431 TI - A case of fibrous hamartoma of infancy in the scrotum including immunohistochemical findings. AB - Fibrous hamartoma of infancy is a benign, uncommon, predominantly fibrous tissue proliferation arising from the subcutaneous tissue during the first 2 years of life. We report a case of fibrous hamartoma of infancy in the scrotum. Clinical and pathological characteristics, including immunohistochemical findings, as well as management are discussed with reference to similar reported cases. PMID- 2197432 TI - Tuberculous cold abscess of the corpus cavernosum: a case report. AB - A rare case of tuberculous cold abscess of the corpus cavernosum is presented. The only presenting symptom was obstructive urinary symptoms caused by external compression of the urethra by the abscess. Diagnosis was reached after surgical drainage and specific antituberculosis therapy led to a satisfactory conclusion. PMID- 2197433 TI - Transrectal prostate ultrasonography as a diagnostic and therapeutic aid for ejaculatory duct obstruction. AB - Preoperative transrectal ultrasonography was used to establish the diagnosis of ejaculatory duct obstruction and also to determine the distal level of extension of the obstructed system within prostatic parenchyma. Transrectal ultrasonography not only established the diagnosis but also enabled precise transurethral resection into the obstructed system. Prostatic ultrasound facilitates evaluation and treatment of azoospermia caused by ejaculatory duct obstruction and may eliminate the need for vasography in such cases. PMID- 2197434 TI - Occult spinal dysraphism: clinical and urodynamic outcome after division of the filum terminale. AB - A highly select group of 31 patients presenting with urinary incontinence failed to respond to conservative management and were found to have unstable bladders and spina bifida occulta. After thorough evaluation they were suspected of having neurogenic bladder dysfunction possibly due to a tethered cord. Following division of the filum terminale daytime incontinence resolved in 72%, urodynamic detrusor hyperreflexia disappeared in 59% and bladder compliance improved in 66% of the patients. The operation was well tolerated and did not result in any neurological complications. The clinical, radiological and urodynamic characteristics of these patients before and after treatment are reported. PMID- 2197435 TI - Effects of the artificial urinary sphincter on prostatic development and sexual function in pubertal boys with meningomyelocele. AB - Although sexual development in boys with meningiomyelocele may progress normally through puberty, the effects of surgical correction of incontinence by insertion of an artificial sphincter device around the bladder neck remain unclear. We studied 13 boys who received an artificial urinary sphincter before puberty and compared them to 12 age-matched pubertal controls with meningomyelocele. The prostate morphology was evaluated by means of transrectal ultrasonography, and we compared this finding, as well as sexual development, erectile function and seminal emissions between the 2 groups. Boys in both groups had similar development of secondary sexual characteristics and reported similar erectile function. Ultrasonography demonstrated an imprint of the sphincter cuff on the prostate but patients and controls had equal prostatic growth. In both groups an unexpected finding was the unexplained presence of sonolucent and sonodense lesions within the prostate glands. We conclude that transrectal ultrasonography is an excellent means of examining the prostate in pubertal boys with meningomyelocele. An artificial urinary sphincter placed around the bladder neck does not alter sexual development, function, prostatic growth or prostatic morphology. PMID- 2197436 TI - Association of type 1 blood group antigens with urinary tract infections in children with genitourinary structural abnormalities. AB - Bacterial adherence to carbohydrate receptors on the surface of urothelial cells is important in the pathogenesis of urinary tract infections. Blood group-related antigens, genetically determined carbohydrate structures found on the urothelial cell surface, may influence the availability of these receptors thereby affecting bacterial adherence and the susceptibility to urinary tract infections. Recent evidence indicates that the immunoanatomical distribution of type 1 blood group related antigens in urothelium is influenced by ABO, Lewis and secretor phenotypes, women with Le(a-b-) and Le(a+b-) blood phenotypes have more than a 3 fold greater risk of recurrent urinary tract infections compared to Le(a-b+) women and epithelial cells from nonsecretors have more bacterial receptors than cells from secretors. To determine the relation between the expression of type 1 blood group-related antigens and urinary tract infections we performed an immunohistochemical analysis using a well characterized panel of monoclonal antibodies on 72 surgical specimens obtained from children who underwent correction of a structural genitourinary anomaly at the University of Rochester Medical Center from December 1983 to May 1988. Of 72 children 48 had a history of at least 1 documented urinary tract infection. The differences in the distribution of children by type 1 blood group immunophenotype in the infection and noninfection groups were highly significant (p = 0.003, Fisher's exact test). There is an increased frequency of urinary tract infections in children with genitourinary structural anomalies whose urothelium reflects the nonsecretor phenotype, that is they have minimal or undetectable levels of ABO and Leb reactivity compared to those with intense ABO and/or Leb immunoreactivity. Of 17 children with minimal or no ABO or Leb immunoreactivity 16 (94.1%) belonged to the infection group. Furthermore, 23 of 24 patients (95.8%) without a history of urinary tract infection expressed intense ABO and/or Leb immunoreactivity. It appears that the type 1 blood group-related antigen profile of urothelium influences susceptibility to urinary tract infection and it may be important in identifying patients who would benefit from prophylactic antibiotic therapy or earlier surgical intervention. PMID- 2197437 TI - Pediatric Urology Medal. Dr. Jack Lapides: clinician, teacher, investigator and innovator. PMID- 2197438 TI - Submucosal injection of polyvinyl alcohol foam in rabbit bladder. AB - Submucosal injection of either polytetrafluoroethylene (Teflon) or collagen has been used in the treatment of vesicoureteral reflux. Although the methods and principles of this treatment are effective, there are concerns regarding the safety and long-term effectiveness of these substances. We present a pilot study to explore the potential of an alternate substance (polyvinyl alcohol foam) for this treatment. Polyvinyl alcohol foam (Ivalon) particles measuring 150 to 250 mu. were injected submucosally into the bladder of New Zealand white rabbits. The bladder was examined macroscopically and microscopically at 1 and 2 weeks, and 1, 2 and 3 months after the injection. The particles created a raised lesion under the mucosa that was visible to the naked eye as late as 3 months after the submucosal injection. The particles remained in a submucosal location after 3 months. At 1 week after injection there was a foreign body giant cell response to the particles. At 3 months the giant cell response persisted and the particles were surrounded by a fibrotic reaction. There was little inflammatory response otherwise. These preliminary results indicate that polyvinyl alcohol foam may be suitable for subureteral injection in the treatment of vesicoureteral reflux. PMID- 2197439 TI - Evaluation of fetal renal function: unreliability of fetal urinary electrolytes. AB - In the fetus with bilateral hydronephrosis it has been reported that a normal volume of amniotic fluid, absence of renal cortical cysts, urinary sodium less than 100 mEq./l., chloride less than 90 mEq./l. and osmolarity less than 210 mOsm. are prognostic factors indicative of good renal function, whereas oligohydramnios, cortical cysts and higher urinary levels of sodium, chloride or osmolarity suggest irreversible renal dysplasia. We report 5 cases in which the fetal urinary electrolytes were not predictive of ultimate renal function. In 3 instances fetal urinary electrolytes and osmolarity were abnormally elevated but the infants survived without ventilatory support. In 2 of these 3 patients the volume of amniotic fluid was normal. Diagnoses included posterior urethral valves, prune belly variant and bilateral ureteropelvic junction obstruction. In 2 cases with oligohydramnios fetal urinary electrolytes were suggestive of satisfactory renal function but the infants died of pulmonary hypoplasia and had bilateral renal dysplasia, prune belly syndrome and urethral atresia. Presently, the volume of amniotic fluid remains the most important prognostic sign in the fetus with bilateral hydronephrosis. Further work is necessary to identify other factors that may be more reliable as prognostic indexes of fetal renal function. PMID- 2197440 TI - Transitional hydronephrosis of the newborn and infant. AB - Between 1986 and 1988, 187 hydronephrotic renal units were discovered antenatally in 134 subjects and confirmed in the neonatal period. Of these cases 119 (64%) were due to anomalies of the ureteropelvic junction. The remainder (36%) were due to various congenital uropathic conditions. Investigation consisted of renal ultrasonography, voiding cystourethrography and diuretic renography with 99mtechnetium-diethylenetriaminepentaacetic acid augmented with furosemide. Of the 119 renal units 36 (30%) underwent pyeloplasty, while 42 (35.7%) were considered normal without obstruction or dilatation. In 41 units (34.3%) diuretic renography showed partial obstruction or dilatation without obstruction that washed out readily with furosemide. Serial renal ultrasonography and renography were performed in these patients. A 12-month followup showed improvement or stabilization in 80% of the renal units and deterioration to significant obstruction in 20%. In attempting to identify the renal units that were most at risk for deterioration, it was realized that the initial ultrasound had a predictive role. None of the mildly hydronephrotic units deteriorated, whereas 14% of the moderately hydronephrotic and 32% of the markedly hydronephrotic units showed further deterioration. However, whether diuretic renography initially demonstrated partial obstruction or dilatation without obstruction, the ultimate outcome could not be predicted. Based on this experience an algorithm is proposed for the evaluation and management of antenatally detected hydronephrosis with currently available imaging techniques. PMID- 2197441 TI - The postnatal management of hydronephrosis diagnosed by prenatal ultrasound. AB - A total of 112 patients (142 kidneys) presented with hydronephrosis consistent with ureteropelvic junction obstruction that had been diagnosed by prenatal ultrasound. The kidneys were classified as having poor, moderate or good function based on isotope imaging at 3 months after birth. Of 9 kidneys that showed poor function 3 recovered sufficient function on pigtail drainage to justify preservation and these patients underwent pyeloplasty. Of 27 kidneys with moderate function 23 also underwent pyeloplasty and 14 of these demonstrated improvement in function postoperatively. Of the 100 kidneys in the good function group that were followed conservatively 23 underwent pyeloplasty during followup primarily because of an observed decrease in function. We propose that there is no indication for immediate pyeloplasty in infants with prenatally diagnosed hydronephrosis who demonstrate good function postnatally. PMID- 2197442 TI - Abdominal aortic aneurysms infected with salmonella: problems of treatment. AB - Seven patients with abdominal aortic aneurysms infected with salmonella organisms were surgically treated between 1985 and 1988. Salmonella culture was obtained from the wall of the aneurysm in every patient, and in five patients it was identified as Salmonella typhimurium. S. choleraesuis and salmonella group D (isolated from this patient but not speciated) were found in the other two remaining patients. Three patients underwent aneurysmal resection with axillofemoral bypass grafting, and three patients were treated by aneurysmal resection with in situ graft; two of this group had the wall and infective periaortic tissue excised. One patient died during the operation as a result of rupture of the aneurysm. Therapeutic doses of antibiotic drugs were given to all of the patients. Although two of the patients in the first group (with the axillofemoral bypass graft) died and the remaining patient had very complicated postoperative course, all the patients in the second group (with in situ graft) survived. We think that in situ graft placement after an extensive debridement of the aneurysmal wall and infected periaortic tissue together with more effective and adequate antibiotic therapy for at least 6 weeks after the operation is a satisfactory method of surgical treatment of this condition. However, graft infection is still a possibility, therefore regular follow-up is needed. PMID- 2197443 TI - Strain gauge plethysmography in the assessment of venous reflux after subfascial closure of perforating veins: a prospective study of twenty patients. AB - Doppler ultrasonography and strain gauge plethysmography were used prospectively to study the hemodynamic changes in 20 patients' (5 men and 15 women) legs operated on by means of subfascial closure for insufficiency of perforating veins. In 10 patients (50%) the valves of the deep veins were incompetent as verified by Doppler ultrasonography, and deep vein thrombosis had previously been diagnosed in seven patients. After subfascial ligature, strain gauge plethysmography showed no changes in arterial flow, venous capacity, or in venous emptying rate. However, both venous reflux flow and reflux volume were significantly lowered (p less than 0.01) after surgery as compared to values before operation. The clinical objective results were good in all cases. In two of four patients with fair subjective results the arterial flow was pathologically high, which probably implies the presence of microscopic arteriovenous fistulas. It is concluded that strain gauge plethysmography can quantitate the change in deep venous reflux after ligation of perforating veins. PMID- 2197444 TI - Variability of Doppler ophthalmic pressure index with occlusive carotid artery disease. AB - To evaluate day-to-day variability of Doppler ophthalmic pressure index by means of the ophthalmomanometry-Doppler technique, bilateral ophthalmic artery pressure and indirect systemic blood pressure determinations were repeated within 1 month in 40 patients with clinically stable occlusive carotid disease. No difference in Doppler ophthalmic pressure and calculated pressure index between both days could be demonstrated. The standard deviation of differences in ophthalmic pressure index between first and second day measurements was 0.04. Correlation between bilateral ophthalmic pressure index measurements on both days was high (r = 0.93, n = 80). It is concluded that individual Doppler ophthalmic pressure index must change at least 0.08 before it can be considered significant. In 37 patients with occlusive carotid artery disease (greater than 60% diameter reduction) undergoing 38 endarterectomies, Doppler ophthalmic pressure index was evaluated before and after surgery. Mean +/- SD ipsilateral Doppler ophthalmic pressure index increased from 0.59 +/- 0.07 to 0.71 +/- 0.05 (p less than 0.001) after endarterectomy. In 12 patients with significant bilateral occlusive carotid disease, mean +/- SD contralateral Doppler ophthalmic pressure index increased from 0.54 +/- 0.05 to 0.61 +/- 0.06 (p less than 0.02), whereas contralateral pressure index in patients with unilateral disease showed no change (0.71 vs 0.71) after ipsilateral endarterectomy. These results indicate that carotid endarterectomy not only normalizes ipsilateral Doppler ophthalmic pressure index but also improves contralateral Doppler ophthalmic pressure index provided significant bilateral occlusive carotid disease is present. PMID- 2197445 TI - Abdominal aortic aneurysm and coronary artery disease: frequent companions, but an uneasy relationship. PMID- 2197446 TI - Research and research funding in vascular surgery. AB - The presentation summarized the current status of funding available for vascular surgeons. In spite of the shrinking support for research by the federal government, there are opportunities for young investigators to pursue an academic career. Success of a grant application depends on preparation, design, and hypothesis. Potential applicants are encouraged to pay special attention to the many publications on how to prepare a research grant. Although there is an increase in participation by vascular surgeons in NIH-supported research, the funding support and focus on vascular surgery remains unsatisfactory. Despite the high ranking of death from aortic aneurysm, there is virtually no funded project on aortic aneurysm in either basic or clinical study. New technology such as laser has received some support, but clinical trial comparing this modality with standard treatment is lacking and not forthcoming. The participation by vascular surgeons in the American Heart Association-funded research activities remains unknown, even though the American Heart Association claims to have spent millions on research in heart and vascular diseases. To promote the study of and research in vascular disease, the members of this distinguished Society need to guide young vascular surgeons to submit grant proposals to various organizations. PMID- 2197447 TI - Scientifically astute activists seek common ground with clinicians on testing new AIDS drugs. PMID- 2197448 TI - From the Food and Drug Administration. PMID- 2197449 TI - Orthopedic research and patient outcomes. PMID- 2197450 TI - Postcoital antimicrobial prophylaxis for recurrent urinary tract infection. A randomized, double-blind, placebo-controlled trial. AB - We conducted a randomized, double-blind, placebo-controlled study to determine the efficacy of postcoital antibiotic prophylaxis in healthy young women prone to recurrent urinary tract infections. Sixteen patients were randomized to receive postcoital administration of a combination product of trimethoprim and sulfamethoxazole, while 11 received postcoital placebo. The treatment groups were similar with respect to age, parity, diaphragm use, history of lifetime urinary tract infections, frequency of intercourse, and number of lifetime sexual partners. In over 6 months of observation, postcoital administration of trimethoprim-sulfamethoxazole was highly effective in preventing recurrent urinary tract infections. Nine of 11 patients who took the placebo developed urinary tract infections (infection rate, 3.6 per patient-year), compared with only two of 16 patients who received postcoital trimethoprim-sulfamethoxazole (infection rate, 0.3 per patient-year). Postcoital administration of trimethoprim sulfamethoxazole was effective in patients with both low (two or fewer times per week) and high (three or more times per week) intercourse frequencies. Side effects were few and compliance was excellent. We conclude that postcoital trimethoprim-sulfamethoxazole is a safe, effective, and inexpensive approach to management of recurrent urinary tract infections in young women. PMID- 2197453 TI - Medical schools in the United States. PMID- 2197451 TI - Impact of the Medicare fee schedule on payments to physicians. AB - Beginning in 1992, the Medicare program will pay physicians by the Medicare Fee Schedule, a system of geographically adjusted standardized payment rates based in part on the Resource-Based Relative Value Scale developed by Hsaio et al and in part on current Medicare payments. In our simulations of the Medicare Fee Schedule, we find that (1) redistributions of Medicare-allowed charges across specialities will be substantial but approximately only half the size projected by Hsaio, (2) there will be large redistributions among geographic areas that tend to compound the specialty redistributions, and (3) there will be wide variation within specialties as to how individual providers are affected. The majority of the redistributive impact of the Medicare Fee Schedule is attributable to implementation of a geographically adjusted system of standardized payments rather than to the particular work values developed by Hsiao et al in the Resource-Based Relative Value Scale. PMID- 2197452 TI - National Institutes of Health Consensus Conference. Surgery for epilepsy. PMID- 2197454 TI - Medical schools in Canada. PMID- 2197455 TI - Tris(2-chloroethyl) phosphate. PMID- 2197456 TI - Disperse Blue 1. PMID- 2197457 TI - Disperse Yellow 3. PMID- 2197458 TI - Vat Yellow 4. PMID- 2197459 TI - 5-Nitro-ortho-toluidine. PMID- 2197460 TI - Nitrilotriacetic acid and its salts. PMID- 2197461 TI - Exposures in the textile manufacturing industry. PMID- 2197462 TI - Chlorendic acid. PMID- 2197463 TI - Chlorinated paraffins. PMID- 2197464 TI - Decabromodiphenyl oxide. PMID- 2197465 TI - Dimethyl hydrogen phosphite. PMID- 2197466 TI - Tetrakis(hydroxymethyl) phosphonium salts. PMID- 2197467 TI - [Pharmacokinetic, bacteriological and clinical studies on aztreonam in neonates]. AB - Pharmacokinetic, bacteriological and clinical studies on aztreonam (AZT) were performed in neonates. The results obtained are summarized as follows. 1. Plasma levels and urinary excretion of AZT were determined in 18 neonates with ages between 1 and 30 days (gestation periods were 36 to 40 weeks and birth weights were 1,890 to 4,300 g) and in 2 infants with 54 and 60 days of age (gestation periods were 36 and 40 weeks, and birth weights were 2,300 and 3,300 g, respectively) upon one-shot intravenous injection of AZT 10 mg/kg (7 cases) or 20 mg/kg (11 cases) to the 18 neonates and 20 mg/kg to the 2 infants. Ampicillin (ABPC) 25 mg/kg was simultaneously injected to 5 cases of the neonates given AZT 20 mg/kg by one-shot intravenous injection and plasma concentrations of ABPC in these 5 cases were also studied. Plasma concentrations in neonates at 0.5 hour after intravenous injection of AZT 10 mg/kg were 11.5 to 27.6 micrograms/ml (average 20.3 +/- 5.5 micrograms/ml) and decreased with half-lives of 2.72 to 5.70 hours (average 3.81 +/- 1.28 hours), and the plasma levels at 8 hours after administration were 3.3 to 8.7 micrograms/ml (average 5.8 +/- 2.5 micrograms/ml). In the cases given AZT at 20 mg/kg, plasma levels at 0.5 hour were 12.4 to 48.8 micrograms/ml (average 35.9 +/- 11.6 micrograms/ml) and decreased with half-lives of 1.69 to 4.14 hours (average 2.94 +/- 0.76 hours) and AZT levels at 8 hours were 1.1 to 10.6 micrograms/ml (average 5.6 +/- 3.6 micrograms/ml). Urinary recovery rates in the first 8 hours after intravenous injection of the 10 mg/kg group were 15.5 to 61.9% (average 37.8 +/- 21.8%) and 16.3 to 62.2% (average 43.5 +/- 16.2%) for the 20 mg/kg group. Plasma concentrations in infants after administration of AZT 20 mg/kg were 33.0 to 35.6 micrograms/ml (average 34.3 +/- 1.8 micrograms/ml) at 0.5 hour and decreased with half-lives of 1.76 to 3.77 hours (average 2.77 +/- 1.42 hours) and AZT plasma levels at 8 hours were 1.4 to 5.8 micrograms/ml (average 3.6 +/- 3.1 micrograms/ml). Urinary recovery rates were 35.4 to 64.8% (average 50.1 +/- 20.8%). These results suggested that AZT shows a dose-dependent, high plasma concentration even in the neonatal period, as well as good urinary excretion from an early stage of the administration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2197468 TI - [Pharmacokinetics and clinical studies on aztreonam in neonates and premature infants (the first report). Study on effectiveness and safety in mono-therapy with aztreonam. A study of aztreonam in the Perinatal Co-research Group]. AB - Pharmacokinetics and clinical study of aztreonam (AZT) in neonates and premature infants were conducted with the following results: 1. Pharmacokinetics (1) Serum concentrations of AZT at 30 minutes after one-shot intravenous injection of 10 mg/kg and 20 mg/kg to neonates including premature infants were 20.6-26.6 micrograms/ml and 38.5-46.4 micrograms/ml, respectively, and decreased thereafter. A dose response was observed in the serum concentrations with administration of AZT 10 mg/kg and 20 mg/kg. (2) Serum half-lives (T1/2) tended to be shorter in both mature and premature infants as their day-ages increased and T1/2 tended to be prolonged in premature infants compared with mature infants. (3) Changes in serum concentration upon one-hour intravenous drip infusion of AZT 20 mg/kg were very similar to those upon one-shot intravenous injection. (4) Urinary excretions in the first 6 hours after one-shot intravenous injection of AZT 10 mg/kg or 20 mg/kg tended to increase in mature infants as they grew and showed excretion rate of 26.2-54.3% but those in premature infants did not show any specific tendency with rate of 17.5-45.1%. Urinary excretions upon intravenous drip-infusion showed a tendency very similar to those upon intravenous injection. 2. Clinical studies (1) Clinically evaluable cases of AZT treatment were 88 cases (91 diseases), in which pathogenic organisms were identified in 56 cases (Group A), i.e., sepsis 9, purulent meningitis 2, pneumonia 8, urinary tract infection (UTI) 33 and others. Total efficacy rate was 98.2% including "excellent" (39), "good" (16) and "fair" (1). Number of cases in which pathogenic organisms were unknown (Group B) was 11, i.e., suspected sepsis (4), pneumonia (3) and intrauterine infection (4) and the efficacy rate was 100% with "excellent" (4) and "good" (7). Thus, both group A and B showed excellent results. AZT was also given to 24 cases for prophylaxis and all the cases showed prophylactic effect of AZT.4+ Bacteriologically AZT was deemed effective in 53 cases out of 56 (Group A) with identified pathogens "eradicated" and "unchanged" (2), thus the bacterial eradication rate was 96.2%. (3) A minor degree of loose feces was observed in 1 (1.3%) of 80 cases as a side effect. Abnormal laboratory test values found were eosinophilia (3 cases), elevation of GOT and GPT (2), platelet-increase (1), elevation of GOT (1), and thrombocytopenia.elevation of GOT.GPT.LDH (1). Every one of these was of a minor degree and transient. From the above pharmacokinetics and clinical results, standard dosage of AZT to neonates and premature infants should be in a unit dose of 20 mg/kg, twice daily to those with ages between 0 and 3 days, and 2 to 3 times daily to those with ages 4 days and above, by intravenous injection or intravenous drip infusion. PMID- 2197469 TI - [Pharmacokinetics and clinical studies on aztreonam in neonates and premature infants (the second report). Study on effectiveness and safety in combination therapy using aztreonam and ampicillin. A study of aztreonam in the Perinatal Co research Group]. AB - Pharmacokinetics and clinical effects were studied in a combination therapy with aztreonam (AZT) and ampicillin (ABPC) in neonates and premature infants. The results obtained are summarized as follows. 1. Pharmacokinetics (1) Average serum concentrations at 30 minutes after one-shot intravenous injection of AZT 20 mg/kg and ABPC 25 mg/kg to a 4-7 days age-group of neonates were 41.3 (AZT) and 30.5 (ABPC) micrograms/ml, respectively. They gradually decreased to 14.7 and 2.7 micrograms/ml at 6 hours after the administration, but the concentration of AZT was always higher than that of ABPC. (2) Serum half-lives (T1/2) in the 4-7 days age-group were 3.61 hours for AZT and 1.42 hours for ABPC, thus T1/2 of AZT was longer. However, T1/2 of AZT was scarcely affected in the concomitant administration of ABPC. (3) Urinary excretion of AZT in the concomitant administration to the 4-7 days age-group was 52.7%, which was the same or a little higher comparing to that in AZT alone administration. 2. Clinical studies (1) AZT and ABPC were concomitantly administered to 160 cases and 133 cases were evaluated for efficacy. Pathogenic organisms were identified in 29 cases (Group A) and the efficacy rate was 86.2% (25/29). The number of cases in which pathogenic organisms were not identified (Group B) was 50 and in this group, the efficacy rate was excellent, 94.0% (47/50). AZT and ABPC were concomitantly administered to 54 cases for prophylaxis and in all the cases the administrations showed prophylactic effect. (2) Bacterial changes were confirmed in 21 of the 29 cases in which pathogenic organisms were identified initially and all of these 21 cases showed bacterial eradication, i.e., the bacterial eradication rate in the treatment was 100%. (3) There were 2 cases in which side-effects were observed among the analyzed 152 cases (1.3%). The side effects found were 1 case each of diarrhea and eruption. Abnormal laboratory values were found in 23 cases (15.9%), i.e., eosinophilia (9 cases), platelet-increase (4), elevation of GOT (4), elevation of GOT and GPT (3) and others (3). From the above pharmacokinetics and clinical results, the combination therapy of AZT and ABPC is considered to be one of the useful empiric antibiotic-therapies when pathogenic organisms are unknown in the infections of neonates and premature infants. PMID- 2197470 TI - [Immunopathological study of proliferation-associated antigens in proliferative skin diseases]. AB - 59 specimens consisting of 10 psoriasis vulgaris, 1 squamous cell carcinoma, 1 Paget disease, 3 keratoacanthomas, 1 pemphigus vulgaris, 18 cutaneous T cell lymphomas, 2 ATLs, and other skin diseases were studied by immunoperoxidase technique. We used four antibodies to demonstrate a cell proliferation-associated antigen (PC, DNA polymerase-alpha and transferrin receptor) and epidermal growth factor receptor. Our observations suggested that the expression of PC and DNA polymerase-alpha may correlate well with cell proliferation, which were demonstrated in the epidermis of psoriasis vulgaris. Primary and metastatic squamous cell carcinoma and some of psoriasis vulgaris had a positive staining for EGF-R, while normal epidermis and almost all other skin diseases were negative. PMID- 2197471 TI - [A case of cutaneous localized cryptococcosis]. AB - A 65-year-old Japanese male with cutaneous localized cryptococcosis, which was developed as an erythematous infiltrated plaque on the right side of the face, was reported. The biopsy specimen taken from the lesion showed a granulomatous change with many spores in the dermis. Culture of the biopsy specimen gave Cryptococcus neoformans serotype D. There were no cryptococcal infections in the other organs. The skin lesion was improved by a systemic administration of miconazole. This patient was unusual since the cryptococcal lesion was limited to the skin, nevertheless he was under a severe cellular immunity deficiency. The reason for this may be that the infected C. neoformans strain belonged to serotype D. PMID- 2197472 TI - [Relation between movement of acid or alkaline proteinase from Trichophyton rubrum and the growth of fungus, pH in medium]. AB - We have previously reported that T. rubrum produced a new type of extracellular proteinase in liquid medium containing bovine serum albumin. This enzyme had an optimal pH 4.5 for azocoll. In this paper, we studied about the relation between movement of acid or alkaline proteinase and environmental pH. In the beginning of cultivation, acid proteolytic activity increased radically, and 3 or 4 weeks later, it was decreased. In place of acid proteinase, alkaline proteinase which had an optimal pH 8.0 was increased gradually. During incubation of T. rubrum in bovine serum albumin medium which was adjusted to pH 6.0, the pH of medium was gradually increased to about pH 7.0 toward 4 weeks. The growth of T. rubrum increased until pH in medium was fixed to pH 7.0. PMID- 2197473 TI - [A case report of hyperosmolar hyperglycemic non-ketotic coma after aortic valve replacement]. AB - A 56-year-old man without a past history of diabetes mellitus underwent aortic valve replacement. On the 8th postoperative day, the patient became confused with a peak blood glucose level of 600 mg/dl and peak serum osmolarity level of 411 mOsm/l, without ketotic urine. The diagnosis of hyperosmolar hyperglycemic non ketotic coma (HHNKC) was made, and the patient was immediately treated with massive infusion of 0.45% saline water and continuous insulin administration, and the patient could completely recover. It is important to prevent and keep in mind the complication of HHNKC for the postoperative care after open heart surgery. PMID- 2197474 TI - [Atrial septal defect with idiopathic thrombocytopenic purpura: a case of open heart surgery]. AB - A 40-year-old woman of atrial septal defect associated with idiopathic thrombocytopenic purpura (ITP) was successfully operated upon under cardio pulmonary bypass. Steroids had been given preoperatively, resulting in an increase of the platelet count from 0.7 X 10(4)/mm3 to 20.6 X 10(4)/mm3. Steroids could be withdrawn before the operation. No bleeding tendency was encountered during and after surgery. This is the 6th case of open-heart surgery associated with ITP in the literature. PMID- 2197476 TI - [Reconstruction of urinary bladder]. AB - Reconstruction of the urinary tract was reviewed. Reconstruction of the ureter dealt with end to end ureteroureterostomy, transureteroureterostomy, bladder flap procedure, psoas hitch procedure, ureterovesiconeostomy, ileal inter position and autotransplantation of the kidney. Bladder augmentation concerned with use of the ileum, ileocecal segment and sigmoid colon, together with artificial material. Reconstruction of the bladder included urinary diversion such as ileal, jejunal, sigmoid, transverse and ileocecal conduit, ureterureterostomy, continent urinary reservoir such as Kock, Mainz and Indiana pouch, and total replacement of the bladder using various segments of intestine anastomosed to the urethra. Surgical endeavor performed by urologists during the past 100 years from 1890 to 1990 was tremendous and it was mainly reviewed from the standpoints of surgical technique and complications. PMID- 2197475 TI - [A case of mediastinal schwannoma originating from the thoracic vagal nerve complicated by early stomach cancer]. AB - Most of primary tumors of the nerves arising in the mediastinum originate from the sympathetic or intercostal nerves. Schwannoma developing from the vagal nerve is very rare. The patient was a 73-year-old male referred to us with abnormal chest X-rays and stomach cancer. One-staged operation was performed by thoracic and upper abdominal median incision. The tumor was removed, which measured 6 X 5 X 4 cm and involved the origin of the left recurrent nerve, by neurectomy. To our knowledge, this was the 18th reported case of schwannoma of the intrathoracic vagal nerve in Japan. A similar schwannoma was observed also in the celiac plexus, and this case was also a rare instance of multiple schwannoma. PMID- 2197477 TI - [Treatment of urological anomalies detected by prenatal ultrasonography]. AB - By the recent advance in ultrasonography, an increasing number of patients with prenatally detected urological anomalies have been reported. Herein, we present 19 cases experienced in the last 3 years in our institution and review the problems in their diagnosis and treatment. In all cases but 2 ultrasonography revealed fetal abnormalities after the 30th gestational week. No cases with abnormal amniotic fluid or severe fetal growth retardation were experienced. No cases were treated in utero. However, 7 cases required an early delivery because of progressive hydronephrosis or enlargement of tumor mass. Postnatally 6 cases were treated by emergency drainage such as percutaneous nephrostomy and placement of an indwelling catheter. However most of the cases with proven urinary tract dilatation were evaluated by diuretic renogram and followed conservatively thereafter. In equivocal cases, pressure-flow study was added. Spontaneous involution of multicystic kidney was also experienced. Erroneous interpretation can occur in fetal diagnosis and the accuracy of prenatal diagnosis was 52.6% in our series. In determining the management of prenatally detected urological anomalies, several factors such as reliability of ultrasonography, fetal renal function, maturity of the lung and the volume of amniotic fluid, must be taken into consideration. Considering the increasing number of fetuses thus detected, it is very important for the pediatric urologists to make consensus on the fetal intervention and postnatal management. PMID- 2197478 TI - [Evaluation of renal function in children with primary VUR up to two years old]. AB - The function of 99 refluxing kidneys of 61 children up to two years old at the time of diagnosis was evaluated by 99mTc-DMSA renoscintigraphy, urinary beta 2 microglobulin (beta 2-MG), alpha 1-microglobulin (alpha 1-MG) and N-acetyl-beta-D glucosamidase (NAG). High grade reflex (grade IV, V) was found in 45% of the cases. 76%, 51% and 92% of the cases showed abnormally high value of urinary beta 2-MG, alpha 1-MG and NAG, respectively. These results indicate that they have already had tubular dysfunction at the time of diagnosis. DMSA renoscintigraphy of 82 refluxing kidneys of 49 children was performed. Of these, 48% had renal scar and 28% had serious renal dysfunction [DMSA uptake rate less than 18%]. 10 20% of low grade VUR had less than 18% DMSA uptake rate. Two patterns were noticed in the group in which urinary beta 2-MG ranged 0.33-1.0. One was characterized by good bilateral renal function with slight tubular damage and the other serious renal dysfunction with fixed tubular damage. No remarkable recovery of the renal function was noticed after antireflux operation in the second pattern cases. In many cases, in which urinary beta 2-MG was more than 1.0, improvement of DMSA uptake rate was noticed after antireflux operation. PMID- 2197480 TI - [Identification of blood vessels using ultrasonic flowmetry during surgery of the abdominal cavity]. PMID- 2197479 TI - [Study of a monoclonal antibody against new epithelial membrane antigens of transitional cell carcinoma]. AB - Immunizing mice with a transitional cell cancer (TCC) tissue in the renal pelvis, we produced a monoclonal antibody (EH14) against new epithelial antigens. After the mice were immunized repeatedly, their splenic cells were harvested and fused with NS/1 myeloma cells. The normal kidney tissue of the same patient was used on Dot blots to select the hybridoma. A a result, one hybridoma whose antibody (EH14) reacted very strongly with TCC but only faintly with normal kidney tissue or normal bladder mucosa was obtained. On immunohistochemistry, EH14 stained all of the 29 TCC tissues. EH14 also stained uterus cancer (7/7) and gastric cancer (6/6) as well as the normal squamous cell and many types of the normal epithelium. All of the lymphnodes containing metastatic bladder cancer were strongly stained with EH14. EH14, however, did not stain interstitial tissues, muscles and sarcomas. The molecular weight of the antigen recognized by EH14 was 14KD and 28 KD on Western blot analysis, and the antigen was stable with formalin or ethanol. The antigen was not the same as that reported previously, and may be useful as a histological marker of TCC. PMID- 2197481 TI - [Restoration of the continuity of the digestive tract after gastrectomy]. PMID- 2197482 TI - [Arrest of massive pulmonary hemorrhage by endobronchial laser photocoagulation]. PMID- 2197483 TI - [Histiocytic proliferative diseases]. PMID- 2197484 TI - [Complications of angiofollicular lymphoma of the duodenum]. PMID- 2197485 TI - [Diagnosis and treatment of cancer of the lung apex (review of the literature)]. PMID- 2197486 TI - [Roentgenologic and endoscopic procedures in the diagnosis and treatment of benign diseases of the biliary tract (review of the literature)]. PMID- 2197488 TI - [Aleksandr Vasil'evich Mel'nikov (on the centenary of his birth)]. PMID- 2197487 TI - [A method of managing the bronchial stump after surgical and combined treatment of patients with cancer of the lung]. AB - The authors developed a complex of measures for the prevention of purulent bronchopleural complications, among which the "stumpless" method of manual treatment of the bronchus is the principal measure. With this method, the incidence of a bronchial fistula reduced to 0.5% in lobe-bilobectomy and to 1.4% in pulmonectomy. Due to the sharp drop in the incidence of this complication, the total postoperative mortality reduced to 3.3%. The developed methods of manual treatment of the bronchus made it possible to level out the difference in the incidence of a bronchial fistula in surgical and combined treatment (preoperative radiotherapy), 2.1% and 3.9%, respectively. The "stumpless" methods of manual treatment of the bronchus in lung carcinoma improve the conditions for oncological radicalism of the operation and prevent economical losses by reducing the hospital stay of patients. PMID- 2197489 TI - [Simultaneous resection with the creation of 2 anastomoses in synchronous multiple primary cancer of the large intestine]. AB - The authors analysed surgical treatment of 26 patients with primary multiple carcinoma of the large intestine with localization of synchronous malignant tumors in distal parts of the large intestine. Eight of these patients underwent one-stage resection of the large intestine with the creation of two anastomoses. Establishment of primary anastomoses during one-stage resections for synchronous primary multiple carcinoma of the large intestine with an AKA-2 compression anastomosis apparatus and a "Skalpel-1" laser device did not deteriorate the immediate results of treatment of this group of patients. One-stage resections of the large intestine are more physiological than subtotal and total colectomy and are sufficiently radical operative interventions. PMID- 2197490 TI - [Treatment of postoperative peritonitis in oncology patients]. PMID- 2197491 TI - [Ways of reducing postoperative mortality and the incidence of suppurative complications in tumors of the large intestine]. PMID- 2197492 TI - Thyroid volume by ultrasound in boys and girls 6-16 years of age under marginal iodine deficiency as related to the age of puberty. AB - The results of thyroid volume estimation with the aid of ultrasound in a total of 921 boys and girls 6-16 years of age are reported. The thyroid volume was found to be increasing slowly between the age of 6 and 12 years, but somewhat more remarkable increase occurred at 13 and 14 years of age. However, in both sexes it was nearly doubled at the age of 15-16 years as compared with the values at 13-14 years irrespective of body weight. The thyroid growth rate (as calculated from the least squares analysis of the correlation between thyroid volume and body weight) in girls was significantly higher (P less than 0.001) than in boys. In spite of long-term mandatory iodine prophylaxis the average urinary excretion of iodine as estimated in 69 randomly selected subjects was 78.06 micrograms/g creatinine (geometrical mean). It may be suggested that such intake of iodine, though marginally deficient, may be satisfactory up to the age of about 12-14 years, while it appeared to be inadequate for the adolescents at the age of puberty. PMID- 2197493 TI - [Various forms of humidifier lung]. AB - Clinical and immunological investigations of 15 workers in a repro-printing house revealed a prevalence of 7% for the occurrence of humidifier-lung. Serological sensitization to humidifier water and fungi respectively was found in 73%, fragmentary symptoms in 53%. In comparison to smokers, elevated antibody levels occurred more frequently in nonsmokers (33% vs. 100%). The results are supposed to reflect subclinical stages of disease, but they are not yet of a definite predictive value. Reduction of microorganisms in humidifiers seems to be essential for the prevention of disease. PMID- 2197494 TI - Toxic shock-like syndrome due to severe hemolytic group A streptococcal infection. AB - A 33-year-old woman suffering from anal erosions developed severe illness with fever, diarrhea, ischalgia, hypotension, acute abdominal pain, dyspnea, renal and hepatic impairment, myalgia, desquamation of the skin, leukocytosis, anemia, hypocalcemia, decreased serum albumin, and cholesterol levels. Exploratory laparotomy did not reveal pathologic findings. Hemolytic group A streptococci were grown from peritoneal swabs and pleural exudate in bacteriologic cultures. The patient slowly recovered after intense penicillin and tobramycin therapy. PMID- 2197495 TI - [Malaria tropica in HIV infection]. AB - This is a case report of a 24 year-old woman who is HIV-infected since three years (stage III B, CDC). She developed malaria tropica during her touristic stay in the Cameroons, Africa. No clinical complications were detectable even though she had a high parasitemia of 18% blood cells infected with Plasmodium falciparum. After quinine therapy defervescence occurred and blood smears were continuously free of malaria parasites. P. falciparum infection may increase HIV related immunosuppression which favours the earlier occurrence of AIDS indicative opportunistic infections. Malaria in combination with HIV-infection can lead to a higher parasitemia; this does not necessarily lead to a higher rate of complications. PMID- 2197496 TI - Transdermal oestrogene application a contraindication in therapy of endometriosis with gonadotropin-releasing hormone analogues. PMID- 2197497 TI - [The category of health as a theoretical problem in aerospace medicine]. AB - This paper presents methods for studying the health of the flying personnel based on systemic approaches. The basic principles of these methods are: improvement of interdisciplinary interaction, use of information systems, automatization of psychophysiological monitoring, etc. Special attention is given to the control of the health status and compensatory capabilities of man exposed to occupation related stress-agents. It is emphasized that the highest priority in medical support of flights should be given to the detection of pre-nosological changes and premorbid states. PMID- 2197498 TI - [Delta-sleep peptide as a modulator of cardiac activity: theoretical recommendations for practice]. AB - In acute and chronic animal (rabbits, rats) experiments it has been shown that delta-sleep producing peptide (DSPP) exerts a noticeable effect on the cardiac function and regulation. DSPP at a dose of 60 nm/kg can prolong the effects of vagus and inhibit those of sympathetic nerves on the cardiac function and, consequently, can influence the function of choline- and adrenergic transmitters. DSPP blocks pressor vascular reactions in response to direct electrical stimulation of ventromedian hypothalamus and thus increases the survival of animals exposed to an acute emotional stress. DSPP normalizes the electrical stability of the heart and produces an antiarrhythmic effect on ventricular ectopic beats that occur in response to emotional stresses. In view of this, DSPP can be recommended for clinical trials as a drug preventing cardiac arrhythmias in stressful situations. PMID- 2197499 TI - [The phenomenon of the adaptive stabilization of cardiac structure and the protection of the heart]. AB - It is known that adaptation to short-term repeated stress-effects may significantly increase human resistance to many factors; it may particularly prevent lethal cardiac fibrillation in the case of acute ischemia and reperfusion of the heart and limit the area of necrotized myocardium in the case of ischemia. The present investigations have shown that the mechanism responsible for this resistance improvement is related not only to neurohormonal factors but also to heart structures as such. Isolated hearts of adapted animals display substantially increased resistance to contractural and arrhythmogenic effects of ischemia and reperfusion, cardio-toxic doses of catecholamines and toxic concentrations of calcium. In all these situations, CPK loss, which is a quantitative characterization of the damage, diminishes as a result of adaptation. Analysis of this phenomenon shows that the structures isolated from hearts of adapted animals, i.e. Ca-pump of the sarcoplasmic reticulum and mitochondria, display a markedly greater resistance to autolysis during prolonged storage. Thus during adaptation to short-term repeated stress-effects the phenomenon of adaptation stabilization of cardiac structures develops at the organ level. This phenomenon is accompanied by an increase in the thermal stability of the heart. From this point of view the role of thermal stress proteins in the phenomenon of adaptation stabilization is discussed and the genetic mechanism underlying the phenomenon is described. PMID- 2197500 TI - [Effect of low-frequency electromagnetic fields on the individual functional systems of the body]. AB - This paper is a review of recent publications about the effects of low frequency electromagnetic fields (EMF) (constant and pulsed) on the cardiovascular, neuroendocrine, and blood systems of experimental animals and industrial workers exposed to them. It is reported that the regulatory systems (nervous and endocrine) are highly sensitive to EMF. It is obvious that investigations of hormone-receptor interactions can help better understand EMF effects on the endocrine system and the body as a whole. Published data about EMF effects on the cardiovascular system and blood are often contradictory, probably, because of different estimates of allowable limits recognized in various countries. It is hypothesized that circulatory changes are largely dependent on the central regulatory structures, particularly hypothalamus. White blood responses to the exposure, being most significant among hematological reactions, are also induced, to a certain extent, by regulatory mechanisms. The EMF effects may depend on the initial state and individual properties of the biological organism. It is postulated that the EMF effects on regulatory mechanisms may be related to primary disorders in cellular and mitochondrial membranes. PMID- 2197501 TI - [Stress and blood circulation in man]. AB - This paper presents the results of studying stress effects on the heart, systemic circulation and cerebral circulation by various methods (ECG, Doppler technique, isotopes, etc). Patterns of circulation changes in response to mental stresses have been identified and variations in circulation regulation as a function of stress enhancement have been revealed. Cerebral circulation changes produced by heavy mental work under stressful conditions are described (increase of blood flow velocity in carotid arteries and of tone of cerebral arteries of large and medium caliber, change in reactivity of anastomoses between branches of the internal and external carotid arteries, patterns of increase and decrease of blood flow in the gray matter of the brain cortex). During prolonged bed rest the type of stressor changes in blood circulation becomes modified and susceptibility to hypertensive states developed. In the course of stressor reactions circulation parameters vary substantially. In this situation changes in systemic circulation are closely related to emotional responses and those in cerebral circulation--to adaptive processes supporting mental activities. PMID- 2197502 TI - The mysteries of the myofibroblast (partially) unmasked. PMID- 2197504 TI - Cell lineages and differentiation programs in epidermal, urothelial and hepatic tissues and their neoplasms. PMID- 2197503 TI - Alpha-smooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing. AB - We have studied the expression of alpha-smooth muscle actin, smooth muscle myosin, and desmin in granulation tissue during the healing of an open wound in the rat by means of electron microscopy and immunohistochemistry, at the light and electron microscopic levels, using specific antibodies directed against these proteins. Important amounts of the three antigens were always expressed in pericytic and/or smooth muscle cells of neoformed small vessels. In fibroblastic cells, microfilaments were absent 4 days after wounding but accumulated gradually, starting from the 6th up to the 15th day; at this time, they were evident in about 70% of fibroblastic cells (myofibroblasts). They then regressed progressively, and on the 30th day, microfilaments were no longer present in scar fibroblasts. alpha-Smooth muscle actin, but not smooth muscle myosin and desmin, was always present in microfilament bundles of myofibroblasts. The staining intensity was progressive from the 6th to the 15th day and decreased thereafter; no staining was seen at the 30th day. Between the 20th and the 25th day, many apoptotic figures were seen in fibroblastic and endothelial cells, suggesting that apoptosis is the mechanism of their disappearance. We conclude that myofibroblasts develop gradually from granulation tissue fibroblasts and temporarily express a marker of smooth muscle differentiation. These results may be relevant for the understanding of the mechanisms of normal and pathologic wound healing. PMID- 2197505 TI - Cutoff of 25 ng/mL for the EMIT d.a.u. phencyclidine assay. PMID- 2197506 TI - Intentional adulteration of urine specimens for drugs of abuse testing to produce false positive results. PMID- 2197507 TI - High level positive end expiratory pressure in a trauma patient with adult respiratory distress syndrome. PMID- 2197509 TI - Models of haemopoiesis. AB - To date, various models have been proposed to explain the diversification of haemopoietic stem cells along one of at least six pathways of differentiation. Consideration of evidence for and against particular models leads to the conclusion that a precise lineage map for the haemopoietic system is, as yet, unavailable. However, recently available cell and molecular biology techniques provide the means to resolve this problem. PMID- 2197508 TI - Modeling the Drosophila pair-rule pattern by reaction-diffusion: gap input and pattern control in a 4-morphogen system. AB - Various reaction-diffusion models will produce striped patterns, but the most effective models so far devised to do this require two matched pairs of interacting morphogens, i.e. four substances in all. This paper examines the behavior of one such model, of a fairly generalized type, and its application to the process of pair-rule pattern formation during Drosophila embryogenesis. It is assumed that the two self-activating morphogens required by the model, expressed in complementary out-of-phase stripes, are products of early-acting pair-rule genes. Possible candidates include the primary pair-rule genes, hairy and runt. The conditions under which regular stripes are generated by the model are then examined, with emphasis on the way pre-existing patterns act to control stripe formation via their effect on rates of reaction within the pair-rule system, specifically rates of pair-rule gene transcription, to show how gap gene products may act during pattern formation. A fully symmetrical set of reactions, in which rates of formation, self- and cross-activation are exactly matched, gives unaligned stripes. Pronounced asymmetries in this regard, e.g. differential rates of formation or self-activation, destabilize stripes or produce local interruptions in the pattern like those seen in gap mutants. A limited degree of asymmetry, coupled with a gradient in the value of one or more parameters will give a correctly aligned, well-controlled pattern of stripes. The experimental evidence indicates that gap genes could be responsible for both of these effects: they activate the pair-rule system asymmetrically and, when first expressed, generate a sufficiently complex landscape of concentration peaks and gradations to provide the local cues needed to correctly position and align the pair-rule stripes. In this respect, the pair-rule system can be viewed as having an intrinsic pattern-forming capability, but it depends on the input of gap genes for pattern control. Gradients are involved, but from this analysis, it is the graded distribution of gap products that is important, not the overall antero posterior gradient. The uniform spacing of stripes, despite underlying peaks and troughs of gap gene expression, shows that pattern wavelength is relatively insensitive to parameter change, also a property of the model.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2197510 TI - Induced differentiation of K562 leukemia cells: a model for studies of gene expression in early megakaryoblasts. AB - The K562 leukemia cell line has been extensively used in studies of erythroid differentiation but it has been less well appreciated that treatment of K562 cells with the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) leads to loss of their erythroid properties and to acquisition of several megakaryoblastoid characteristics. These include synthesis and surface expression of glycoprotein IIIa, an increase in platelet peroxidase positivity, enhancement of thromboxane A2 receptors, and increased cell volume and DNA ploidy. TPA treated K562 cells also synthesize and secrete platelet derived growth factor (PDGF), transforming growth factor beta 1 (TGF beta 1), urokinase-plasminogen activator (u-PA) and its specific inhibitor, type 1 plasminogen activator inhibitor (PAI-1). Induction of all these proteins, which have also been found in platelet granules (u-PA on platelet surface receptors) occurs at the level of mRNA accumulation. Therefore, in addition to facilitating studies and cloning of genes specific for erythroid differentiation, the K562 cells offer a tool to approach early steps of megakaryoblast commitment and differentiation. Observations made with the K562 cell line and several other leukemia cell lines co-expressing erythroid and megakaryocyte markers suggest that the erythroid and megakaryocyte lineages diverge from a common bipotent precursor cell. PMID- 2197511 TI - Abortion law in England: the medicalization of a crime. PMID- 2197513 TI - The "crisis" in medical malpractice: a comparison of trends in the United States, Canada, the United Kingdom and Australia. PMID- 2197512 TI - HIV screening: nosocomial epidemiologic risks and decision analysis. PMID- 2197514 TI - History of the Alabama dental hygiene program. PMID- 2197516 TI - GM-CSF: intravenous versus subcutaneous treatment. PMID- 2197515 TI - Mechanisms of growth factor expression in acute myeloid leukemia (AML). AB - To investigate possible mechanisms of growth factor expression in acute myeloid leukemia, genes for granulocyte macrophage colony-stimulating factor (GM-CSF) were analyzed by Southern blots in 20 patients, for M-CSF in 13, for interleukin 6 (IL-6) in 14, for IL-6 receptor in 14 and for G-CSF in five patients. Only in one patient a complex rearrangement of the G-CSF gene with possible amplification was noted indicating rarity of direct alterations of growth factor genes in acute myelogenous leukemia (AML). Spontaneous m-RNA expression for GM-CSF was found in only one of 20 patients, and for IL-6 in eight of 11 patients. In vitro incubation of AML cells of eight patients with recombinant tumor necrosis factor for 24 hr revealed induction of GM-CSF m-RNA expression in three cases and GM-CSF protein expression in two of them. These data suggest that spontaneous GM-CSF production occurs rarely in AML and that monokines, such as tumor necrosis factor, may induce GM-CSF in AML cells. Therefore, interactions of AML cells with normal or malignant accessory cells may be important for autocrine stimulation in AML. Our data suggest that ectopic growth factor secretion is not the primary cause of generating AML but may contribute to progression of the disease. Alternatively, AML may represent a heterogenous group of leukemias with different etiology but similar phenotype. PMID- 2197517 TI - Computer-assisted radiology--requirements and solutions for digital diagnostic imaging. AB - More and more digital imaging equipment is used in the daily routine of radiology departments. Computerized diagnostic equipment provides new capabilities for radiologists. It provides improvement of the work flow within the department, of the exchange of information between radiologists and referring physicians, and the exchange of information between radiologists specialized in specific diagnostic procedures. This exchange of information has to be performed locally within the department, between different buildings belonging to one department or between widely separated buildings in different hospital. The penetration of 'computer-assisted radiology' makes the organization of an imaging department and the information to be handled within it more and more complex. Specific requirements result from this increasing complexity. To meet these requirements, Siemens has developed technical solutions for integrated digital diagnostic imaging. These solutions allow the functional integration of physically separated systems such as multiple computed tomography (CT) units or CT plus magnetic resonance (MR) units belonging to one department, centralized archiving, hard copy generation and image display, rapid access to images from multiple locations and effective image communication for intensive care units, child care units and trauma patients. Some of these requirements are discussed and the corresponding products are described. It is shown how these solutions will migrate to future comprehensive picture archiving and communication systems (PACS) configurations. PMID- 2197518 TI - Building two medical databanks. AB - Two medical databanks are described: one for poison control centres, and one for gastroenterology. They include a diagnostic system built up since 1961 with logistic and statistical trial solutions, barring symptoms and the addition of not-found symptoms in the first data processing of the files. Up to 40 questions are answered by the databank concerning poisons. Around 60,000 items of information are stored. The databank for gastroenterology took 50 man-years for its development. 1381 diagnoses and 35,750 symptoms are now stored, with 445 test cases. Answers for 22 questions are provided. The correct diagnosis is found in 84% and 87% respectively in the first line of the printout; nearly 90% seems possible. PMID- 2197519 TI - Absorption characteristics of insulin through the buccal mucosa. AB - The purpose of the study was to investigate absorption characteristics of insulin through the buccal mucosa by studying the influence of application time of the buccal cell on the hypoglycemic response as well as the plasma insulin level. Three application times of the buccal cell (0.5, 1.0 and 1.5 h) were studied. A marked increase in the extent of hypoglycemia was observed when the application time was extended from 0.5 to 1.0 h. Correspondingly, the amount of insulin absorbed increased in the same order. However, a further increase in application time from 1.0 to 1.5 h did not seem to significantly enhance the hypoglycemic response. This finding was also confirmed by the insulin blood levels. It can be suggested that a certain amount of time is required for insulin molecules to be taken up by the buccal mucosa. Tmax of hypoglycemia was observed about 1.0 h after the removal of the cell, irrespective of the application time. Absorption profile of plasma insulin was found to be application time-dependent. These results can be attributed to the reservoir function of the buccal mucosa and time dependent equilibrium of insulin with the buccal mucosa. PMID- 2197520 TI - [The ultrasonic picture of the abdominal vessels in focal lesions of the liver]. AB - Ultrasound investigation of the abdominal vessels was conducted in 41 patients with liver tumors (17 patients with liver hemangiomas, 9 with primary liver cancer, and 15 with cancer metastases to the liver) and 100 controls. Shifting, compression, occlusion of the intrahepatic portal and hepatic veins as well as of the inferior vena cava and right renal vessels were observed in patients with malignant and benign liver tumors. Malignant tumors were accountable for shifting and compression of the extrahepatic segment of the portal vein and the upper mesenteric artery as a result of metastatic involvement of the lymph nodes. Statistically significant dilatation of the total hepatic artery was noted in patients with malignant and benign liver tumors, determined, probably, by an increase in the arterial inflow in the liver. A decrease in a degree of change of calibers of the portal and hepatic veins in malignant liver tumors was noted in patients with hepatocellular cancer, developing against a background of cirrhosis with portal hypertension as well as in patients with secondary malignant tumors without clinical signs of portal hypertension that might result from an obstacle posed by tumor nodes in the liver parenchyma to venous wall dilatation. PMID- 2197521 TI - [238Pu body distribution in dogs after intravenous administration and early complexon therapy]. AB - The paper is concerned with the assessment of the level and concentration of 238Pu in different organs and tissues of dogs after iv injection of 238Pu-citrate at the amount of 92.5 kBq.kg-1 and during early complexon therapy. Ninety per cent of Pu detected in the body was shown to be deposited in the skeleton and liver in the ratio 4.5:1. The concentration of 238Pu in per cent to 1 g of tissue in the critical organs (the skeleton, liver, bone marrow) was (28.7--46.9) X 10( 3)%. The concentration of the radionuclide in the organs and tissues regarded as uncritical, was 1-2 orders lower: the endocrine organs--(0.7--7.5) X 10(-3)%, the lymph nodes--(3.8--5.4) X 10(-3)%, the G. I. tract portions--(1.05--1.5) X 10( 3)%, the CNS portions--(0.1--2.0) X 10(-3)%; the kidneys, muscles, heart, spleen and lungs--(0.63--8.8) X 10(-3)%. Early use of octacine or pentacine decreased Pu concentration in all investigated organs and tissues 2 +/- 0.06 times on an average. The efficacy of octacine was no inferior to that of pentacine. PMID- 2197523 TI - [The comprehensive diagnosis of osteogenic sarcoma]. PMID- 2197522 TI - [A method for the integrated echo and x-ray contrast study of the uterus]. PMID- 2197524 TI - Histoplasma capsulatum infections of the central nervous system. A clinical review. AB - Central nervous system manifestations occur in 10 to 20% of patients with disseminated histoplasmosis. Additionally, histoplasmosis may be the cause of cases of chronic meningitis in patients with no other evidence for dissemination. Histoplasmosis may also cause cerebral or spinal cord mass lesions resembling neoplasms or abscesses, and encephalitis. Diagnosis of chronic meningitis or mass lesions caused by H. capsulatum may be difficult and involves careful analysis of serologic tests for antibodies, cultures and tests for HPA in body fluids. Amphotericin B remains the treatment of choice, but relapses occur in half of cases despite total courses of at least 35 mg/kg. Accordingly, careful long-term follow-up is required to identify patients with relapsing infection. Newer antifungal agents which cross the blood brain barrier are needed. A trial of amphotericin B treatment without surgical excision can be justified in patients with cerebral or spinal cord histoplasmomas, in view of the apparent success of such treatment in a few cases. Progression of clinical abnormalities or persistence of the lesion following completion of treatment would support the need for surgical excision. PMID- 2197525 TI - [Relation between the energy parameters and the free pool of polyamines in Escherichia coli during synchronous growth]. AB - The cell cycle of Escherichia coli is characterised by synchronous oscillations in the levels of ATP and putrescine. Oscillations in the pool of putrescine are determined by ATP content which exerts a strong stimulating effect on the activity of ornithine decarboxylase, the key enzyme of polyamine synthesis. The results allow one to consider the system of polyamine synthesis as a point in the regulatory interaction (coupling) between the constructive and energetic types of E. coli metabolism. PMID- 2197526 TI - [Storage of Pseudomonas strains degrading the surfactants]. AB - The survival rate and the destruction activity of Pseudomonas strains decomposing anionic and ampholytic surfactants were studied in the course of their storage for a long period of time. The strains were shown to remain viable and active after being freeze-dried for a year. Therefore, lyophilisation can be recommended as the main method of storage for bacterial strains decomposing the following surfactants: sulfoethoxylate, sulfonate, cyclimide, and amidobetaine. PMID- 2197527 TI - [Electrophysical analysis of the damage of Escherichia coli outer membrane]. AB - The method of electro-orientational spectroscopy was used to study the damaging action of SDS and Triton X-100 on Escherichia coli cells in which the barrier properties of the outer membrane were impaired by treatment with Triton B (10(-2) M Tris-HCl buffer, pH 8.0) and a heat shock (47 degrees C, 15 min). When either SDS (10(-4)-2.10(-4) M) or Triton X-100 (10(-4)-10(-3) M) was added to such cells, the high-frequency region of their electroorientational spectrum was found to undergo considerable changes. The mode of these changes indicated that the barrier properties of cell cytoplasmic membranes were damaged. These changes were not detected in the case of intact cells. Changes in the low-frequency region of the spectra for intact and damaged cells stemmed from the adsorption of these surfactant molecules on the cell surface. PMID- 2197528 TI - [Physiological properties of Saccharomyces cerevisiae during sine-modulated and stepwise changes in the medium pH]. AB - The responses of a chemostat Saccharomyces cerevisiae culture (D = 0.1 h-1) to a stepwise increase or decrease in the pH of the medium were shown to be asymmetric. When the pH was lowered from 6.5 to a value above 0.3, the rates of oxygen uptake and carbon dioxide evolution rose for a sort period of time whereas the optical density of the culture fell down. The detected changes in the properties of the culture were identical with those which had been observed in the course of spontaneous undamped oscillations in the physiological parameters of the continuous C. cerevisiae culture. Apparently, in both cases, the energy status of cells changed when the oxidative type of metabolism was substituted by fermentation. When the pH of the medium was elevated within the same range (4.7 6.5), the response of the culture was three times as low and its properties changed in the opposite direction. When the pH of the medium was changed in a cyclic sinusoidal manner, oscillations in the physiological characteristics of the culture, identical with spontaneous oscillations were induced at certain values of the amplitude and the frequency of pH changes. PMID- 2197529 TI - [Smoking and health]. PMID- 2197530 TI - [Passive smoking]. PMID- 2197531 TI - [Use of pentamidine in protozoan diseases]. PMID- 2197532 TI - [Lung deposition of 300 and 600 mg pentamidine, inhaled with 3 different inhalers]. AB - Intracorporal, especially pulmonary, and extracorporal deposition of pentamidine was studied following inhalation of 300 or 600 mg in 6 ml Aqua dest. each dose in six patients with one previous episode of pneumocystis carinii pneumonia. Three different nebulizers--two mechanical nebulizers (Respirgard II and Pari-IS-2) and one ultrasonic device (Portasonic) - were compared. The following results were obtained: 1.300 mg pentamidine in 6 ml Aqua dest. is a sufficient dose for prophylaxis provided an appropriately constructed nebulizer and an optimal respiratory manoeuvre (inspiratory vital capacity breathing) are employed. With the nebulizer Portasonic, the frequency of cough was higher compared with the two mechanical nebulizers, which is attributed to its higher mist density. 2. Application of 600 mg pentamidine in 6 ml Aqua dest. as an aerosol is difficult to apply owing to clinical and technical problems caused by severe respiratory tract irritation and a high viscosity of the nebulizer solution. We assume that ultrasonic nebulization is affected more by the high viscosity than mechanical pneumatic nebulization. 3. Inspiratory vital capacity breathing (12/min) leads to five- to eight-fold higher pulmonary and improved peripheral deposition rates compared with commonly used spontaneous respiration. We therefore recommend to shorten the duration of inhalation by applying this respiratory technique while maintaining a generally tolerated and optimally nebulizable concentration of pentamidine, i.e. about 300 mg in 6 ml Aqua dest. PMID- 2197533 TI - [Unwanted drug side effects with pentamidine inhalation]. AB - The incidence of systemic side effects under aerosolized pentamidine treatment or prophylaxis for pneumocystis carinii pneumonia is low when compared to intravenous application. Erythema, hypotension, hypoglycemia, renal failure are infrequently seen. Local side effects--cough, bronchial spasm, metallic taste- are frequent complications of aerosolized pentamidine treatment. Cystic lung disease, pneumothorax, and atypical pneumonia may be a late sequelae of pneumocystis carinii pneumonia, and not a primary effect of pentamidine. Poor apical ventilation due to suboptimal inhalation technique etc. and decreased deposition of pentamidine in these areas may be of some consequence for the development of these unusual complications. Extrapulmonary pneumocystis infections under preventive pentamidine aerosol treatment for pneumocystis carinii pneumonia have been seen in single cases, a causal relationship to pentamidine application is not yet established. PMID- 2197534 TI - [Therapy of HIV associated mild and moderately severe Pneumocystis carinii pneumonia with 600 mg/die pentamidine aerosol. Results of a multicenter study]. AB - In 22 HIV positive patients a mild to moderate pneumocystis carinii pneumonia was treated by daily inhalation for 21 days of 600 mg pentamidine, divided into two inhalation phases with the inhalation of 300 mg pentamidin each. In 13 patients (59%) treatment was successful. In five cases, therapy was stopped in the first treatment week because of lacking clinical effectiveness resp. clinical deterioration. In four cases, therapy was discontinued in the further course. The subsequent treatment was successful in all cases. In the case of otherwise good tolerance, in two cases there was a hypoglycemia, in one case with clinical signs. In no case there was any sign of an extrapulmonary pneumocystosis. PMID- 2197535 TI - [Treatment of mild to moderately severe Pneumocystis carinii pneumonia with cotrimoxazole versus pentamidine aerosol. Preliminary results of a prospective randomized therapy study]. AB - In an open, prospective, randomized study we compared efficacy and side effects of 8 g/d cotrimoxazole (TMP/SMX) i.v. vs. 600 mg aerosolized pentamidine. 29 of 60 planned case record forms are now evaluated. Efficacy in both groups was comparable, but side effects in the pentamidine arm were very rare (7.2% vs. 40% in the TMP/SMX group). In moderate pneumocystis carinii pneumonia aerosolized pentamidine could be the first choice therapy. Necessary conditions are to use proper inhalation systems, experience, and the treatment of relevant accompaning bacterias, which we found in 80% of pneumocystis carinii positive bronchoalveolar lavages. PMID- 2197536 TI - Primary prevention of Pneumocystis carinii pneumonia by inhalation of pentamidine. Preliminary results from a placebo-controlled randomized trial. Swiss Group for Clinical Studies on AIDS. AB - Patients with AIDS but without pneumocystis carinii pneumonia, patients with advanced AIDS-related complex (ARC), and asymptomatic patients with less than 200 CD4-positive lymphocytes/mm3 were randomized to one of two groups: group I: Inhalation of 300 mg of pentamidine every 28 days; group II: Inhalation of placebo (300 mg of Na isethionate) every 28 days. From May to November 28, 1989, 160 patients have entered the trial. Inhalations were well tolerated, with only a 6% use of bronchodilators and a 15% incidence of cough. Until now five patients died, none of them drug related. So far, six patients have developed pneumocystis carinii pneumonia; four of these were on pentamidine, and two on placebo. Five of the six cases occurred before the second inhalation. Recruitment will continue until 250 patients are enrolled. PMID- 2197537 TI - [Preventive pentamidine inhalation of Pneumocystis carinii pneumonia in patients with immune deficiency. Preliminary evaluation of a multicenter study]. AB - In the first evaluation of an uncontrolled multicenter study on inhalative pentamidine prophylaxis (300 mg pentamidine-isethionate monthly) of pneumocystis carinii pneumonia in immunocompromised patients, 48 patients (all 48 patients HIV1-infected, 36 without preceding pneumocystis carinii pneumonia (primary prophylaxis), twelve after pneumocystis carinii pneumonia (secondary prophylaxis); age 20 to 68 years (median 38); 45 male, two female, one unknown; 22 patients AIDS) were observed for 0 to 8.5 months (mean 4 +/- 2 months, intended observation time twelve months). No proven pneumocystis carinii pneumonia was found in the observed patients. One patient was treated with cotrimoxazole because of a suggested pneumocystis carinii pneumonia-relapse, which could not be proven. Out of seven (14.6%) patients, whose therapy was discontinued, three patients died, three refused further therapy, one patient had a relapse of a cerebral toxoplasmosis. Six patients (12.5%) reported adverse reactions (cough, metallic or bitter taste, slight nausea). New opportunistic infections appeared in four patients (8.3%). PMID- 2197538 TI - [Randomized comparative study of secondary prevention of Pneumocystis carinii pneumonia in patients with acquired immunologic deficiency syndrome]. AB - Pneumocystis carinii pneumonia is one of the most frequent infectious complications in patients with the acquired immunodeficiency syndrome (AIDS). A prospective trial was initiated to compare azidothymidine alone with azidothymidine plus aerosolized pentamidine as a secondary prophylaxis for pneumocystis carinii pneumonia. 27 patients (24 male, three female, average age 39 years) were enrolled, 14 patients receiving azidothymidine and pentamidine aerosol and 13 azidothymidine alone. After 166 days of follow-up, this trial had to be terminated prematurely, since the efficacy of pentamidine aerosol in the prevention of pneumocystis carinii pneumonia was clearly demonstrated in two recently published studies. Two patients died during the study period, one in either group, but neither due to pneumocystis carinii pneumonia. Two patients developed histologically proven pneumocystis carinii pneumonia; both patients were allocated to the azidothymidine arm. Pneumocystis carinii pneumonia was suspected clinically but not proven in four patients, three were randomized in the azidothymidine arm. Pentamidine was well tolerated and produced no severe side effects. The sample size is too small to draw definitive conclusions concerning the efficacy of pentamidine aerosol in AIDS patients. PMID- 2197539 TI - [The evolution of dental echography: clinical and experimental research. The ultrasonic anatomy of the teeth and periodontal tissues]. AB - Early clinico-experimental findings with real-time B-mode Echography of the odontological district are reported. On the basis of previous in vitro application references and using a unidimensional A-Mode technique, preliminary data of in vivo ultrasound semeiotics regarding the tooth and its periodontal structures are outlined experimentally. Although current "in vivo" experience relates exclusively to front central and para-central teeth, it can be hypothesised that further technical and methodological developments of echographic instruments may permit systematic employment of ultrasound diagnosis in the odontological sector. PMID- 2197540 TI - [The maxillofacial prosthesis: palatal obturators. The principles of treatment and rehabilitation in a case of buccorhinosinusal communication]. AB - Having analysed the causes which lead to the loss of substance from the palatal vault, the different types of communication which then result, their evolution and the consequent functional defects are identified. By describing a complex clinical case, and having taken into consideration both aims and materials, the techniques of prosthetic rehabilitation are illustrated using obturator devices. The results of the various phases are examined. PMID- 2197542 TI - [The diagnosis and treatment of traumatic root fractures of the coronal third in the mature permanent anterior teeth]. AB - Diagnostic and treatment implications of traumatic root fractures in the coronal third of permanent anterior teeth are reported. A review of the literature imposes a reevaluation of the treatment of these fractures. The teeth with root fractures should not be extracted and endodontic therapy should not be performed unless there is evidence of a pulp necrosis. The authors suggest trying a conservative treatment by repositioning, fixation and relief of occlusion of the teeth with fractures. The fixation is maintained over six months to improve the possibility of recovery. The clinical cases presented prove the long-term prognosis is good even if the location of fracture is near the gingival crevice. The conservative treatment doesn't preclude in case of failure, endodontic, orthodontic and prosthetic therapy. Moreover, according to the authors, conservative treatment represents the most simple, immediate and physiologic solution of functional aesthetic and psychologic problems, especially in young patients. PMID- 2197541 TI - [Stomatomucositis due to the chemo- and radiotherapy in the treatment of malignant hemo- and lymphopathies]. PMID- 2197543 TI - Marginal leakage of restorations using a glass-ionomer liner in bonding composite resins to dentin. PMID- 2197544 TI - Fungal infections in patients infected with HIV. AB - HIV-positive patients are at risk for a number of serious fungal infections. The author reviews the common fungal infections and stresses the importance of early detection and appropriate treatment. PMID- 2197545 TI - Improving perinatal outcome for rural Missouri. AB - Improving perinatal outcome in rural Missouri as reflected by a lowering of the perinatal mortality rate is a realistic and achievable goal for the state. The authors present information and data with suggestions for reaching this goal. PMID- 2197546 TI - Medicolegal aspects of testicular torsion. AB - Testicular torsion is a surgical emergency which requires prompt exploration, detorsion, and bilateral orchiopexy. The authors present information helping to explain why testicular torsion often leads to lawsuits for physicians. PMID- 2197547 TI - Serious infections caused by coagulase-negative staphylococci in intravenous drug users. AB - While Staphylococcus aureus has been a well-recognized pathogen in patients who use illicit intravenous drugs, coagulase-negative staphylococci are not generally appreciated as causes of infectious complications in intravenous drug users. The authors present data suggesting the coagulase-negative staphylococci are potential pathogens in these high risk patients. PMID- 2197548 TI - [Human genetics, today and tomorrow]. PMID- 2197549 TI - [The significance of imaging procedures]. AB - Pediatric imaging today is mainly characterized by avoiding ionizing radiation. In this regard magnetic resonance imaging and ultrasonography are most suitable modalities. Compared to other methods--radiography, CT, nuclear scans and angiography--the importance of MRI and ultrasonography as primary or supplementary diagnostic tools for various organ systems--CNS and spinal canal, musculo-skeletal system, thorax, abdomen, small parts--are emphasized. As demonstrated in other western countries integrated diagnostic imaging in pediatrics must be the pediatric radiologist's chief task also in our hospitals. PMID- 2197550 TI - [Evaluation of a modified immunomagnetic procedure for the purging of neuroblastoma cells from bone marrow]. AB - The immunomagnetic depletion method for removing tumor cells from bone marrow, previously refined using a Burkitt lymphoma model, was tested with neuroblastoma cells. The efficiency of depletion was quantified by immunofluorescence with a detection limit of 3.3 log of cell depletion corresponding to the elimination of 99.84% of an initial tumor cell content of 10%. A panel of five monoclonal antibodies (UJ13A; UJ127.11; UJ181.4; alpha-Thy1; H11) purged 2.8 log of SKNBE and LAN-1 cells, while two of these antibodies as single agents allowed only for a 1.7 log (UJ13A) and a 1.7 to 2.0 log (alpha-Thy1) depletion. This underlines the advantage of an antibody panel for neuroblastoma purging. The new antibody S L 11.14, an IgG2a against small cell lung cancer which recognizes 90% of neuroblastoma cells purged 2.8 log. PMID- 2197551 TI - [Color-coded Doppler sonography of the kidney blood vessels in childhood. II. Pathological findings]. AB - Pathologic flow profiles in renal arteries can be found in cardiovascular and renovascular disease. Obstructions of the left hart (aortic stenosis, hypoplastic left heart syndrome, coarctation of the aorta) cause diminished flow with low peak systolic velocities. In renal arteries of infants with leakage of the aortic "Windkessel" (persistent ductus arteriosus, truncus arteriosus communis etc.) a low diastolic amplitude can be found. Significant left-to-right shunts can lead to a diminished or even retrograde diastolic flow. In renal artery stenosis a high velocity jet with spectral broadening can be found in the region of the stenosis. Distal to the stenosis low blood flow velocities can be shown. In renal vein thrombosis the obstruction of the peripheral vessels cause a missing or even negative diastolic flow in the renal arteries, whereas venous blood flow is diminished or even missing. Kidney diseases with swelling of the organ (acute rejection of a transplanted kidney) can cause diminished, missing or even retrograde diastolic flow in the renal arteries dependent on the severity of the edema. These alterations can be used for the early diagnosis of acute rejection which offers the opportunity for early and efficient therapeutic management. PMID- 2197552 TI - Effects of vanillin and o-vanillin on induction of DNA-repair networks: modulation of mutagenesis in Escherichia coli. AB - Vanillin and its isomer o-vanillin have an effect on the adaptive and SOS responses, as well as mutagenesis, induced in Escherichia coli by N-methyl-N nitrosourea (MNU) and UV irradiation, potentiating in some cases and suppressing in others. o-Vanillin markedly inhibited the MNU-induced adaptive response, while both vanillins potentiated the UV-induced SOS response. These phenomena appear to be responsible for the comutagenic or antimutagenic role of these chemicals in MNU and UV mutagenesis. PMID- 2197553 TI - Frequency of spontaneous and induced recessive mutations in a diploid strain of Aspergillus nidulans. AB - The spontaneous and UV-induced frequencies of recessive mutations have been studied in a diploid strain of Aspergillus nidulans, by the p-fluoro phenylalanine (FPA) and 8-azaguanine (8-AZA) resistance tests, on either resting or germinating conidia. Observed frequencies are in the order of magnitude of those expected, which have been calculated considering the observed mutation frequencies in the haploid strain as well as the mitotic recombination frequencies. We also review some papers which claim to have found higher rates of recessive mutations in mammalian cell lines; in some cases no really higher rates are evident and the authors' conclusions often rest on misinterpretation of their own data. PMID- 2197554 TI - Drinking and flying--the problem of alcohol use by pilots. PMID- 2197555 TI - Reactions to the stings of the imported fire ant. PMID- 2197556 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 33-1990. A 72-year-old Chinese woman with recent abdominal pain and a right-sided abdominal mass. PMID- 2197557 TI - Editorial position vacant. PMID- 2197558 TI - Striking conservation of TFIID in Schizosaccharomyces pombe and Saccharomyces cerevisiae. AB - Eukaryotic promoters contain binding sites for basic transcription factors and gene-specific activator proteins. The transcription factors interact at the TATA box, which lies close to the position of transcription initiation. Activators typically bind to distant sites that can lie kilobases away from the initiation site. The factor TFIID binds specifically to the TATA box to initiate an ordered pathway of assembly of the basic transcription factors. Biochemical analyses have shown that human and Saccharomyces cerevisiae TFIID are functionally interchangeable in vitro. To study further the functional conservation of this critical factor, we are surveying proteins from divergent organisms that can substitute in vivo for the S. cerevisiae TFIID. We report here the isolation of a unique gene from Schizosaccharomyces pombe that fully complements a null mutation in SPT15, the gene that encodes TFIID in S. cerevisiae. The Schiz. pombe gene encodes a protein 93% identical (166/178) to S. cerevisiae TFIID in a region consisting of a direct repeat. PMID- 2197559 TI - First UK trial of AIDS vaccine approved. PMID- 2197560 TI - No evidence for expression of the insulin-regulatable glucose transporter in endothelial cells. AB - A major effect of insulin is to increase glucose transport in muscle and fat. A family of genes encoding distinct mammalian glucose transporters has recently been elucidated. One of these, the insulin-regulatable glucose transporter (IRGT), is primarily expressed in muscle and fat, tissues that exhibit insulin dependent glucose transport. Insulin promotes glucose transport in these tissues by stimulating movement of the glucose transporter from an intracellular location to the plasma membrane. Recent studies, however, suggest that an additional effect of insulin in these tissues may be the facilitation of glucose transport, presumably across capillary endothelium. This hypothesis is based on the localization of the IRGT in endothelial cells specific to muscle and adipose tissue. We report here, however, on morphological and biochemical studies using several different IRGT-specific antibodies in which we could not reproduce these results. PMID- 2197561 TI - Arabidopsis thaliana contains two genes for TFIID. AB - The general transcription initiation factor TFIID plays a primary part in the activation of eukaryotic genes transcribed by RNA polymerase II. Binding of TFIID to the TATA box initiates the assembly of other general transcription factors as well as RNA polymerase II at the promoter resulting in a preinitiation complex capable of accurate transcription initiation in vitro. Human TFIID has been shown to interact with various regulatory factors. The observation that stimulation of transcription by different trans-acting factors is mediated through distinct TATA elements led to the suggestion that different types of TFIID may exist in yeast, humans and plants. Here we report the cloning and characterization of two distinct TFIID complementary DNA clones from Arabidopsis thaliana. Furthermore, we have found that TFIID from Arabidopsis and other organisms shows homology to helix-loop-helix proteins. PMID- 2197562 TI - Spontaneous shuffling of domains between introns of phage T4. AB - The three self-splicing introns in phage T4 (in the td, sunY and nrdB genes) (Fig. 1a) each have the conserved group I catalytic RNA core structure (Fig. 1b), out of which is looped an open reading frame. Although the core sequences are very similar (approximately 60% identity), the open reading frames seem to be unrelated. Single crossover recombination events between homologous core sequences in the closely linked td and nrdB introns have led to 'exon shuffling. Here we describe spontaneous double crossovers between the unlinked td and sun Y introns that result in shuffling of an intron structure element, P7.1 (refs 3 and 4). The intron domain-switch variants were isolated as genetic suppressors of a splicing-defective P7.1 deletion in the td intron. This unprecedented example of suppression through inter-intron sequence substitution indicates that the introns are in a state of genetic flux and implies the functional interchangeability of the two analogous but nonidentical P7.1 elements. The implications of such recombination events are discussed in the light of the evolution of the introns themselves as well as that of their host genomes. PMID- 2197563 TI - [Dutch ticks as vectors of infectious diseases]. PMID- 2197564 TI - [Deep venous thrombosis in pregnancy: diagnosis, treatment and prevention]. PMID- 2197565 TI - [Risk factors for the development of side effects during treatment of rheumatoid arthritis with second-line antirheumatic agents; a review of the literature]. PMID- 2197566 TI - [Neurotraumatology in ancient Egypt]. PMID- 2197567 TI - [Chronic hydrocephalus in adults]. AB - The aim of this study is to sum up our current knowledge on the so-called "normal pressure hydrocephalus" syndrome, revisited by the authors as the "adult chronic hydrocephalus" syndrome (A.C.H.). It is based upon 1) a review of the literature dealing with the subject (518 references) and 2) an original series of 243 cases summarizing a 10 year experience of 2 french neurosurgical teams (Lyon: 123 cases, Clermont-Ferrand: 120 cases). Part I is devoted to the review of pathologic and pathophysiologic data. Both autopsy and microscopic findings clearly show 2 categories of anomalies in the brains of patients showing this condition: "non specific" lesions may be either causative (leptomeningeal thickening, villositar sclerosis) or secondary to hydrocephalus (ependymal wall disruption, sub-ependymal "edema"). Conversely, "specific lesions" are either degenerative (Alzheimer-type) or ischemic in origin. They seem unrelated to hydrocephalus, but may play a role in the ventricular enlargement by favoring changes in brain elastic properties. Data available from brain biopsies (13 cases) have confirmed the high incidence of such "specific lesions" of the parenchyma. Following the Hakim's initial hypothesis, several mechanisms have been proposed to explain the progressive ventricular dilation despite a fall in C.S.F. pressure. Experimental and clinical data (namely those referring to the pathogenesis of secondary A.C.H.) are reviewed. The sequence of events following acute ventricular obstruction is analysed. The ultimate state of chronic uncompensated hydrocephalus involve multiple factors among which a trans-cerebral mantle pressure gradient may play a major role. The intervention of compensatory mechanisms (reduction of C.S.F. production, establishment of alternative pathways of C.S.F. absorption) is also discussed. Part II is devoted to the presentation of the clinical material. Series of the literature including more than 20 surgical cases are briefly reviewed together with the authors' material and methods. Criteria of selection of patients, methods of clinical evaluation and of statistical analysis of results are exposed. Of the 243 patients of the present series, 225 were managed by C.S.F. shunt (V.A.: 137, V.P.:60, L.P.:28). Results were as follows (mean follow-up:31 mths +/- 28): good results (including excellent results): 128 (52.6%), fair: 52 (21.3%), poor and aggravated: 49 (20%), early deaths: 14 (5.7%), 12 of those post-operatively. The rate of surgical complications was 35% (S.D.H.: 16.8%, sepsis: 4%, seizures: 4%, shunt malfunction: 10.6%) leading to reoperation in 25.7%. Long-term survival rate was 75% (172 alive patients and 57 late deaths).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2197568 TI - [The beginning of experimental nephrology? The bilateral nephrectomies of J.N. Comhaire in 1803]. PMID- 2197569 TI - [Biological markers of allograft rejection]. AB - The main cause of graft failure is rejection. Beside clinical manifestations of graft dysfunction, biological markers of graft rejection have been proposed. These are biochemical markers related to inflammatory response or lymphocyte activation (cytokines, thromboxane B2, beta 2 microglobulin, neopterin) and cellular markers. Cells may be obtained from peripheral blood, the graft itself or urine, biliary or pancreatic fluid. Phenotypic (IL2 receptors, HLA DR, CD4, CD8) or functional (mitotic index, cell specific cytotoxicity) properties have been studied. Numerous markers have been proposed but few of them are specific enough and routinely used. PMID- 2197570 TI - [Physiopathology of idiopathic calcium lithiasis]. AB - In this review article the various steps and local mechanisms of stone formations are summarized. Then the pathophysiology of the various risk factors namely urinary excretion of calcium, oxalate, uric acid, urine volume, urine pH and urinary inhibitors of stone formation is extensively discussed. PMID- 2197571 TI - [High dose chemotherapy in malignant gliomas using autologous bone marrow transplantation and GM-CSF: granulocyte-macrophage colony stimulating factors]. PMID- 2197572 TI - [A case of cerebral cysticercosis: cyst growth is confirmed by CT scan during 6 years of follow-up]. AB - A rare case of a 40-year-old woman with cerebral cysticercosis is reported. She has lived on the Island of Tokunoshima and has never travelled overseas. She was hospitalized in the hospital of Kagoshima University in 1980. A small cyst in the right temporal lobe, and a calcified area in the left parietal lobe was noticed on CT scan. When she was admitted to our hospital in December 1986, the cyst in the right temporal lobe was larger than it was 6 years before. An operation was performed for the cyst in the right temporal lobe. The cyst was pathologically confirmed as cysticercosis. Postoperatively, immunological reaction of cysticercosis was positive, but X-rays and CT scan of extremities showed no abnormal findings. Cerebral cysticercosis is a rare disease in Japan. CT scan is very useful in the diagnosis of this disease. Multiple cysts and calcified area in the parenchymal region are specific findings on CT scan. PMID- 2197574 TI - [Therapeutic aspects of the polycystic ovary]. PMID- 2197573 TI - [The use of LHRH analogs in gynecologic oncology]. AB - The use of LHRH analogues in gynecological oncology is related to the capacity of these compounds to determine pharmacological sterilisation which represents an alternative to surgical ovariectomy in the treatment of hormone-sensitive carcinoma. The modes of administration, metabolism and mechanisms of action of these drugs are illustrated. A section of the action of these drugs are illustrated. A section of the work is dedicated to the side-effects; they are divided into adverse effects, in the accepted meaning of the term, and the consequences of secondary hypoestrogenism. The paper concludes with the presentation of experimental data, both in animal studies and in vitro, which are the basis for the use of analogue therapy in the treatment of advanced stage breast cancer. PMID- 2197575 TI - [A case of primary ovarian pregnancy in an IUD-wearing patient]. AB - A case of primary ovarian pregnancy in a patient fitted with an IUD is reported. Anatomic, pathological, clinical, etiological and therapeutical aspects of ovarian pregnancy are discussed with reference to published data. The case study presented in this paper shows the characteristics aspects of this pathology of pregnancy: the patient is a multipara, fitted with an IUD; clinical diagnosis was intraoperatively and adnexectomy was chosen as the most appropriate treatment. Anatomic and pathological tests were used to confirm the diagnosis of ovarian pregnancy. PMID- 2197576 TI - [Epidemiologic evaluation of precursors of cervix cancer, early diagnosis and treatment]. PMID- 2197577 TI - Glial cell intrusions actively remove detritus due to toxic chemicals from within nerve cells. AB - It has been observed that when neurons are acutely damaged by toxic chemicals leading to accumulations of effete materials, glial supporting cells insert cytoplasmic processes into neuronal cytoplasm and appear to transfer this material into themselves. Essentially the same phenomenon has now been seen in several situations, namely in peripheral nerve axons in a number of experimental peripheral nerve intoxications, especially in spinal roots, as well as occasionally in normal axons in paranodal regions and more frequently above a nerve ligation. It has been seen, too, in cerebellar Purkinje cells after acrylamide intoxication and in hippocampal pyramidal neurons and in neurons of the pyriform cortex after triethyllead and trimethyltin intoxications. A similar process may also be taking place regularly both in normal and chemically damaged spinal ganglion cells through their satellite cell sheath. While probing of neurons by glia has also been noted normally in pre-synaptic regions of mammalian neurons as well as in the perikarya of certain goldfish neurons, the purpose for this is less apparent. Such findings in relation to removal of bulk residual material from neurons raise intriguing questions as to the signals required between cells to enable such evidently cooperative intercellular events to take place, and whether this process, that is apparently so inefficient in removing lipofuscin pigment from ageing neurons, may not, perhaps, be adversely influenced by environmental agents. PMID- 2197578 TI - Stereospecificity of N-MDA-induced functional deficits. AB - Male Fischer-344N rats were pretreated bilaterally with intrahippocampal (D) (-) 2-amino-7-phosphonoheptanoic acid [(D)-2-APH] (2.5, 5.0 and 10 micrograms/site), a competitive N-methyl-d-aspartate (NMDA) antagonist, prior to the administration of bilateral N-MDA (10 micrograms/site). (D)-2-APH completely attenuated NMDA induced hyperactivity and water maze acquisition deficits. (D)-2-APH also attenuated hippocampal pyramidal and granule cell loss induced by NMDA. These effects were stereospecific since pretreatment of the isomer L-(+)-2-APH (10 micrograms/site) had no effect on hyperactivity and water maze acquisition deficits produced by NMDA. In addition, (L)-2-APH provided no protection from NMDA-induced hippocampal granule and pyramidal cell loss. Together, these results suggest that the intrahippocampal administration of NMDA might serve as a useful in vivo model for evaluating the effects associated with the overactivation of NMDA receptors. PMID- 2197579 TI - The effects of 2,5-hexanedione on the retina of albino rats. AB - Male Sprague-Dawley rats received 1% 2,5-hexanedione in their drinking water for a period of 5 weeks. The rats were by this time paralyzed in the hind limbs. Half of the rats were then sacrificed while the remaining rats were allowed to recover for 13 weeks. A control group of rats were housed and fed under identical conditions and were studied in parallel. The axonal changes in the optic pathways and the abnormalities of the retina were examined histologically in all groups including immuno-peroxidase staining with antibodies for neurofilament proteins. The retinas of the rats sacrificed immediately following treatment showed a reduction of the outer nuclear layer and the outer and inner segments of the rods and cones as compared with the controls (p less than or equal to 0.01). The rats permitted recovery for 13 weeks and then sacrificed had lost almost completely their rods and cones (p less than or equal to 0.001). Some of the rats had a small residue of the rods and cones at the Ora Serrata. No decrease in the thickness of any other retinal layer was seen. Swellings of the axons in the optic pathways and of the axons innervating the iris were discerned in the treated rats. There was no evidence of an inflammatory response in the retina to the cell loss at any time. Whether this lethal damage to the rods and cones is caused by the 2,5-hexanedione alone or in combination with light energy remains to be elucidated. PMID- 2197580 TI - Interactions between lead and essential elements: a review. AB - Young children are especially susceptible to the toxic effects of lead. Although the effects of overt lead intoxication have been well studied, critical information on the long-term effects of low level lead exposure is lacking. The results of recent clinical studies indicate that "chronic" low level lead exposure during development can result in behavioral alterations in the absence of overt neurotoxicity. The perturbation of central nervous system functioning may be the result of essential mineral deficiencies resulting from lead-induced impairment of mineral availability and/or an increased sensitivity to lead in the absence of adequate levels of essential minerals. This article reviews research undertaken to examine the interactions between calcium, iron, zinc, copper and lead with reference to how this may impact central nervous system functioning. PMID- 2197581 TI - [Serum ferritin--a tumor marker in malignant lymphomas?]. AB - Serum ferritin concentration as a tumor associated marker was investigated in 535 patients with malignant lymphomas. The study included 207 patients with Hodgkin lymphomas, 196 patients with low grade malignant Non Hodgkin lymphomas and 132 patients with high grade malignant Non Hodgkin lymphomas of different tumor stages. Increased serum ferritin concentrations were found in 54% of the unselected patients. In particular, serum ferritin concentration was elevated in 12.3% of patients with stage I, in 33.8% of patients with stage II, in 72.2% of patients with stage III and in 94% of patients with stage IV. The serum ferritin levels correlated with the tumor mass. There was no difference between Hodgkin lymphomas and Non Hodgkin lymphomas. In patients with concomittant hepatocellular disease or during chemotherapy inadequate high serum ferritin concentrations were found, which did not correlate with tumor mass. In patients with primary bone marrow infiltration by some low grade malignant Non Hodgkin lymphomas serum ferritin levels correlated better with the tumor stages according to Rai than with the Ann-Arbor-classification. The serum ferritin concentration followed closely the activity of the disease: Increased pretreatment serum ferritin levels normalized completely, when patients achieved complete remission. In contrast, in patients with tumor relapse or tumor progression serum ferritin levels increased again. The data suggest that the serum ferritin concentration can be used for follow-up of patients with malignant lymphomas. Because of its limited specifity and low sensitivity it cannot be used as a screening test. Nevertheless, it is a helpful additional parameter for the control of the activity of the disease. PMID- 2197582 TI - Improved tolerance of interferon alpha-2a by continuous subcutaneous infusion. AB - Fifteen patients with progressing melanomas, hypernephromas or B-cell malignancies were treated in a phase I study with Interferon (IFN) alpha-2a by continuous subcutaneous infusion. With the help of a syringe driver pump daily doses of 12-15 MU resulting in median weekly doses of 90 MU could be safely given with little side effects. Flu-like symptoms and side effects from the gastrointestinal tract were mainly of grade 1 or 2 only. The major dose limiting but reversible toxicity was leukopenia. Five patients developed local inflammatory reactions at the infusion site. The pharmacokinetic data demonstrate that by this route of administration median serum levels of 54 IU/ml (range 9.6 192.0 IU/ml) (EIA-F-assay) can be achieved. Antibody formation was observed in 4 patients. - One out of 9 patients evaluable for tumor response demonstrated a partial tumor regression and 4 patients had a stabilisation of their disease. In comparison to intermittent i.m. or s.c. schedules, this novel route of administration by continuous subcutaneous infusion results in significant serum concentrations, biological activity and little clinical side effects. This may facilitate in the future the combination of IFN alpha-2a with other biological response modifiers like interleukin-2 or tumor necrosis factor. PMID- 2197583 TI - Preoperative immunostimulation with propionibacterium avidum KP-40 in patients with gastric carcinoma: a prospective randomized study. AB - Sixty-eight patients admitted for resection of gastric carcinoma entered a prospectively randomized trial. Patients in the therapy group (n = 34) received a preoperative controlled infusion of 10 mg Propionibacterium avidum KP-40. The therapy and control group did not differ with regard to postoperative complications, tumor recurrence rates (therapy group: 41%, control group: 38%), and patient survival rates (survival rate in the therapy group after 25 months: 53%, in the control group after 25 months: 50%). PMID- 2197584 TI - [Breast cancer in the male--a retrospective analysis of 15 cases]. AB - We report about 15 cases of cancer of the male breast treated within the period 1972-1988 at the Surgical Department of the Hanusch-Krankenhaus, Vienna. Patients age ranged from 38 to 82 years, averaging 61.7 years. After a median follow-up period of 40 months (ranging from 1-171 months) two-thirds of our patients had died, 40% from the primary disease. In cases with a follow-up period of more than 5 years, only 1 out of 11 patients is still alive, 6 of them having died in the meantime. In 40% of our patients the first symptom noticed was a painful lump accompanied by gynecomastia. Seven patients out of 15 (i.e. 46.6%) had been treated previously with aldosterone antagonists of spironolactone type. Except for 1 patient who had had X-ray radiation in the past, no other exposure to possible risks could be observed. A multicentre data input and central processing of generic data for the evaluation of optimal treatment of this rare disease is desirable. PMID- 2197585 TI - Interleukin-2 in combination with interferon-alpha in disseminated malignant melanoma and advanced renal cell carcinoma. A phase I/II study. AB - In vitro, the combination of interleukin-2 (Il-2) with interferon-alpha (IFN alpha) seems to act synergistically on the generation of lymphokine activated killer (LAK) cells. Due to this fact two clinical trials with the combination of Il-2 and IFN-alpha were initiated in malignant melanoma (MM) and renal cell cancer (RCC). Patients with disseminated MM were treated by a sequential application of 10 x 10(6) U/m2 rIFN-alpha 2b s.c. on days 1-7 followed by continuous intravenous infusion of 3 x 10(6) U/m2 rIl-2 on days 8-13 and 15-20. After a pause of 4 weeks the cycle was repeated. In advanced or disseminated RCC, the patients were treated with a daily alternating scheme of 10 x 10(6) U/m2 rIFN alpha and rIl-2 as 1 h infusion 1 x /day for 14 days. The rIl-2 escalates intra- and interindividually beginning with a dose of 3 x 10(6) U/m2. The cycles were repeated after a pause of 3 and 4 weeks, respectively. The preliminary results show that the schedules are practicable and that the toxicity of the combination of rIl-2 and IFN-alpha does not accumulate. Within the MM group 3/11 evaluable patients achieved partial remission and 2/11 stable disease. In the RCC-group 2/5 evaluable patients achieved partial remission and 2/5 had stable disease so far. PMID- 2197586 TI - Ethical considerations in phase I clinical trials. AB - Medical ethics has developed methods of differential ethics for a more rigid integration of bioethical reasoning into biomedical research. Due to high levels of risk and uncertainty in phase I trials, established principles of medical ethics need a specific assessment in order to provide for better moral design and moral monitoring of trial procedures, a better translation of medical health status data into individual quality of life criteria, and strong support for trust-based cooperation between physician, research team and patient. Existing bioethical questionnaires and detailed methodological research in differential ethics could be improved further. PMID- 2197587 TI - Statistical requirements of phase I studies. AB - Methodological aspects of planning and evaluating phase I studies in oncology- the link between preclinical research and approval of clinical efficacy--include the human starting dose, maximum tolerable dose and dose escalation schemes. Statistical requirements of phase I studies are presented here, emphasizing the urgency of their application in current practice. For the maximum tolerable dose a distinction will be made between an individual- and a population-based approach, which is crucial for a correct definition and statistical parameter estimation. Weaknesses of the dose escalation scheme according to the modified Fibonacci scheme are shown and contrasted with the recently proposed pharmacokinetically guided dose escalation. Comprehensive phase I/II information processing is recommended for validating current practice. PMID- 2197588 TI - [Overdose with melphalan (Alkeran): symptoms and treatment. A review]. AB - The symptomatology and outcome of three of our own cases with Melphalan overdose are presented. The literature regarding Melphalan overdose and its toxicity when given in normal and high doses is reviewed. Two of our cases with injection of less than 100 mg/m2 recovered from marrow aplasia within 3 weeks without major complications. The third patient died 6 days after injection of 290 mg/m2 Melphalan, probably due to cardiac arrhythmia before complete marrow failure had established. After intravenous application of more than 125 mg/m2 gastrointestinal side effects such as hemorrhagic diarrhea or even bowl perforation may be observed. These, together with a syndrome of inadequate ADH secretion and electrolyte disturbances were the predominant clinical problems and the reasons for early death before infectious or bleeding complications due to prolonged marrow aplasia occur. Therapeutic measures are discussed. Due to the lack of a clinically useful antidote and detoxification method only symptomatic treatment is recommended. Colony stimulating factors such as GM-CSF G-CSF may improve the prognosis of moderate to severe Melphalan overdose. PMID- 2197589 TI - Sclerokeratitis after keratoplasty in atopy. AB - The authors report a series of five markedly atopic patients in whom a severe sclerokeratitis developed within 1 to 4 weeks of keratoplasty. The onset was acute with discomfort, photophobia, hyperemia, and mucus production. This resulted in early loosening of sutures and was associated with microbial keratitis in two cases and graft rejection in one. The inflammatory reaction was controlled with high-dose oral steroids and did not recur when the treatment was terminated. Serum IgE levels were elevated in all these patients (range, 421-8434 kU/l). Binding of this IgE onto the surface of mast cells in the conjunctiva with subsequent degranulation may be involved in the pathogenesis of the induced inflammation. Principal recommendations include the use of interrupted sutures and early immunosuppression with high-dose oral steroids at the onset of this condition together with the control of risk factors for microbial keratitis. PMID- 2197590 TI - Pleomorphic adenocarcinoma of the ciliary body. Immunohistochemical and electron microscopic features. AB - An 80-year-old man was evaluated for an epibulbar tumor on a phthisical eye. The initial biopsy diagnosis of the epibulbar tumor was poorly differentiated neoplasm. Exenteration of the phthisical eye and orbital contents showed an extensive pleomorphic adenocarcinoma of the nonpigmented epithelium of the ciliary body with extraocular extension. There was evidence of hyaluronic acid secretion and immunohistochemical staining was strong for vimentin, focal for epithelial membrane antigen and S-100 protein, and weak for neuron-specific enolase. Electron microscopy demonstrated desmosomes between tumor cells, areas of thick, multilaminar basement membrane production surrounding individual tumor cells, and occasional intracytoplasmic intermediate filaments. PMID- 2197591 TI - Detection of ras gene mutations in human lung cancers by single-strand conformation polymorphism analysis of polymerase chain reaction products. AB - A simple, sensitive method of DNA analysis of nucleotide substitutions, namely, single-strand conformation polymorphism analysis of polymerase chain reaction products (PCR-SSCP analysis), was used for detection of mutated ras genes in surgical specimens of human lung cancer. Of a total of 129 tumors analysed, 22 contained a mutated ras gene. Of the 66 adenocarcinomas analysed, 14 contained an activated c-Ki-ras2 gene (the mutations in codon 12 in 6, in codon 13 in 4, in codon 18 in one, and in codon 61 in 3), one contained a c-Ha-ras1 gene with a mutation in codon 61 and 3 contained N-ras genes with mutations (in codon 12 in one and in codon 61 in 2). Mutated rats genes were also found in 2 of 36 squamous cell carcinomas (c-Ha-ras1 genes with mutations in codon 61) and 2 of 14 large cell carcinomas (c-Ki-ras2 genes with mutations in codon 12). No mutation of the ras gene was detected in 8 small cell carcinomas and 5 adenosquamous cell carcinomas. These results indicate that activation of the ras gene was not frequent (17%) in human lung cancers, that among these lung cancers mutation of the ras gene was most frequent in adenocarcinomas (27%) and 73% of the point mutations were in the c-Ki-ras2 gene in codon 12, 13, 18 or 61. PMID- 2197592 TI - The Ha-ras protein, p21, is modified by a derivative of mevalonate and methyl esterified when expressed in the insect/baculovirus system. AB - Using the insect/baculovirus expression system, we demonstrate the incorporation of [3H]mevalonate and [3H]methyl groups into recombinant c-Ha-ras protein (p21). Unlike the post-translational palmitoylation of p21 expressed in this system, the modification by mevalonate is not removed by hydroxylamine suggesting the absence of a thioester linkage. It is highly likely that the insect expression system recognizes the C-terminal CAAX Motif in p21, incorporates the mevalonate into the recently described polyisoprenylation modification and carboxyl-methylates the protein. PMID- 2197593 TI - [Spontaneous fluctuation of extracellular matrix molecules on the surface of human skin fibroblasts in culture: flow cytometric analysis]. AB - The evolution of five surface markers (CD 10, fibronectin, collagens I, III, IV) was analysed in cytofluorometry after immunolabelling of cultured human skin fibroblasts. The expression of the CD10 molecule and collagen IV remained stable. On the contrary, there was a spontaneous variation of the cell surface distribution of fibronectin and collagens I and III. This variation was periodical and followed the subculture rhythm. After every passage, the density of matrix components increased at the cell surface. The maximum of the density was achieved on confluent fibroblasts then decreased until the next passage. The fibronectin and collagens I and III expression was permanently altered on senescent fibroblasts. Modifications of the expression of extracellular matrix proteins on the fibroblasts surface were closely linked with cellular density and senescence. PMID- 2197594 TI - [The role of a parathyroid hormone analogue in the pathogenesis of malignant hypercalcemia]. AB - Patients with malignant hypercalcemia can display not only an increase in bone resorption, but also changes in the renal tubular reabsorption of calcium and phosphate similar to those found in primary hyperparathyroidism. A protein of tumoral origin likely responsible for this syndrome has been described. Even if produced by another gene than parathyroid hormone, it shares a homology in the aminoterminus and seems to exert a similar spectrum of action. Besides its role in malignant hypercalcemia, this analogue may be involved in physiological regulatory processes. PMID- 2197595 TI - Detection of latent sequence periodicities. AB - A method is proposed for the automatic detection of serial periodicities in a linear sequence. Its application to DNA subtelomeric sequences from two lower eukaryotes, P.falciparum and S.cerevisiae, reveals ordered patterns organised in hierarchical periodicities, not easily recognizable by other methods. The possible implications concerning the evolution of tandemly repetitive arrays are discussed in light of a model which involves, as successive steps, random repeat modification, the fusion of differently modified repeat versions into longer units, and the amplification of (and/or homogenization to) the more recent repeat units. PMID- 2197596 TI - MutY, an adenine glycosylase active on G-A mispairs, has homology to endonuclease III. AB - The mutY gene of Escherichia coli, which codes for an adenine glycosylase that excises the adenine of a G-A mispair, has been cloned and sequenced. The mutY gene codes for a protein of 350 amino acids (Mr = 39,123) and the clone genetically complements the mutY strain. The protein shows significant sequence homology to E. coli endonuclease III, an enzyme that has previously been shown to have glycosylase activity on damaged base pairs. Sequence analysis suggests that, like endonuclease III, MutY is an iron-sulfur protein with a [4Fe-4S]2+ cluster. PMID- 2197597 TI - An F factor based cloning system for large DNA fragments. AB - An effective technique using an Escherichia coli plasmid system was developed to clone fragments of exogenous DNA of as large as 100 kilobase pairs. The characteristic features of this technique are the use of a low copy number (one to two) mini-F based plasmid vector and the introduction of artificial lambda cosR ends into the termini of DNA sources and then of the cosL ends into those of linearized vector molecules. This terminal modification greatly facilitated the formation of active large recombinant molecules, which was rarely achieved when the modification was omitted. The efficiency with which large recombinant clones can be generated is high enough to allow construction of a comprehensive library of higher organisms. All analyses of the plasmids recovered have revealed that the inserts were faithful replicas of the human DNAs used as sources. PMID- 2197598 TI - The tL structure within the leader region of Escherichia coli ribosomal RNA operons has post-transcriptional functions. AB - We have investigated a series of mutations within a plasmid encoded E. coli ribosomal RNA leader region. The mutations are localized within a structure known as tL, which has been shown to mediate RNA polymerase pausing in vitro, and which is assumed to have a control function in rRNA transcription antitermination. The effects of the mutated plasmids were analyzed by in vivo and in vitro experiments. Some of the base change mutations led to severely reduced cell growth. As opposed to previous results obtained with mutants where the tL structure has been deleted in part or totally, the tL base change mutations did not result in polar transcription in vivo, rather they revealed a general reduction in the amount of the promoter proximal 16S versus the distal 23S RNA. The deficiency of the 16S RNA, which was most pronounced for some of the slowly growing transformants, can only be explained by a post-transcriptional degradation. In addition, many mutants showed a defective processing after the initial RNase III cut. In line with these results a quantitative analysis of the ratio of ribosomal subunits and 70S tight couple ribosomes showed a reduced capacity to form stable 70S particles for the slowly growing mutants. Together, these findings indicate an important function of the tL structure in post transcriptional events like processing of rRNA precursors and correct assembly of 30S subunits. PMID- 2197599 TI - The upstream activating sequence for L-leucine gene regulation in Saccharomyces cerevisiae. AB - The upstream activating sequence (UAS) conferring leucine-specific regulation of transcription in Saccharomyces cerevisiae was identified by analysis of the LEU2 promoter and by comparison to other genes regulated by leucine. The UAS was localized with deletions and cloned synthetic DNA. Point mutations and sequence rearrangements were used to identify important basepairs and to construct an improved UAS with increased regulation and expression. The improved UAS contains a core ten basepair, GC-rich, palindromic sequence, which is sufficient to confer minimal levels of activation and regulation, within a 36 basepair palindromic sequence which confers maximal activation and regulation. Deletions downstream of the UAS indicated that the UAS must act in conjunction with at least one other site, perhaps a TATAA region, in order to confer high levels of activation. Tandem copies of the UAS in front of LEU2 increased expression and regulation. Tandem UAS elements in trans on a multi-copy 2 mu-based plasmid decreased expression and regulation. These results are consistent with a model that the UAS serves as the DNA-binding site for diffusible activation factor(s), possibly the LEU3 gene product. PMID- 2197600 TI - DNA polymerase I and a protein complex bind specifically to E. coli palindromic unit highly repetitive DNA: implications for bacterial chromosome organization. AB - Starting from a crude E. coli extract, two activities which specifically protect highly repetitive bacterial DNA sequences (called PU for Palindromic Unit or REP for Repetitive Extragenic Palindromic sequence) against a digestion with Exonuclease III have been purified. We show that one of these activities is due to the DNA polymerase I (Pol I). This constitutes the first indication for a specific interaction between Pol I and a duplex DNA. This interaction requires the presence of PU. It was confirmed and analyzed by native gel electrophoresis and DNase I footprinting experiments. The other activity contained at least five polypeptides. Its binding to PU DNA sequences was confirmed by native gel electrophoresis. Implications for the possible origin and functions of PU are discussed. PMID- 2197601 TI - Evidence that covalent complex formation between BCNU-treated oligonucleotides and E. coli alkyltransferases requires the O6-alkylguanine function. AB - Chloroethylnitrosoureas (CENUs) are thought to induce cytotoxic DNA interstrand cross-links via an initial reaction at O6-position of guanine, yielding a rearranged intermediate, O6,N1-ethanoguanine. Repair of these adducts by mammalian and bacterial DNA alkyltransferases blocks the formation of cross links. Human alkyltransferase can form a covalent complex with DNA containing BCNU-induced cross-link precursors, but the nature of the DNA-protein linkage remains unknown. Using E. coli alkyltransferases expressed by the ada and ogt genes, we now demonstrate that both enzymes can form such complexes with CENU treated DNA. We attribute this reaction to the O6-alkylguanine repair function, because an N-terminal fragment of the ada protein, which has only alkylphosphotriester repair activity, failed to form a similar complex. This result is consistent with the idea that complex formation requires an alkyltransferase reaction with a guanine adduct, such as O6,N1-ethanoguanine. It tends to exclude the possibility that such reactions simply involve alkylation of the enzyme by reactive DNA adducts such as chloroethylphosphate or chloroethylguanine. PMID- 2197603 TI - Nucleotide sequence involving murG and murC in the mra gene cluster region of Escherichia coli. PMID- 2197602 TI - Nucleotide sequence of the 32 kDa-protein gene (antigen 85 A) of Mycobacterium bovis BCG. PMID- 2197604 TI - Nucleotide sequence of a cDNA coding for mouse cyclophilin. PMID- 2197605 TI - Nucleotide sequence of the Saccharomyces cerevisiae CLN1 and CLN2 genes. PMID- 2197606 TI - Porcelain inlay: a historical view. PMID- 2197607 TI - Review of dentinal bonding in vitro: the substrate. AB - This article reviews common substrates and testing conditions used in dentinal bond strength studies in vitro. The available literature supports the use of freshly extracted, hydrated human teeth for studies in vitro. No one testing condition has proven superior accuracy over the others. Evidence is presented to support the implementation of infection control measures when handling the substrates. PMID- 2197608 TI - Turning towards the father. PMID- 2197609 TI - Fumes from the spleen. PMID- 2197610 TI - Methodological considerations in research on child sexual abuse. AB - Child sexual abuse research presents practical, methodological and statistical challenges. This paper examines some recent literature about the incidence and effects of child sexual abuse. Researchers who use epidemiological studies to attempt to ascertain the prevalence of different forms of abuse should be aware of the different populations studied, different methodologies used, diverse definitions of sexual abuse and practical limitations on participants' memories. Common problems in retrospective and prospective studies into the effects of child sexual abuse include the use of atypical populations, inappropriate statistical analyses, the use of unvalidated psychometric instruments and limited sources of information on child functioning. Attention must also be paid to potentially confounding demographic and family variables. A thorough understanding of, and attention to, these problem areas in child sexual abuse research will give a clearer picture of the prevalence and effects of abuse, thus indicating the most appropriate forms of prevention and treatment. PMID- 2197611 TI - Fractures of the base of the fifth metatarsal distal to the tuberosity. PMID- 2197612 TI - Chondroblastoma of bone. PMID- 2197613 TI - Radiologic case study. Periosteal osteosarcoma. PMID- 2197614 TI - [Clinical autopsies: allowed, necessary, prohibited?]. PMID- 2197615 TI - [Oncocytic hepatocytes]. PMID- 2197616 TI - [ABO incompatibility: on immunohistochemistry of fatal transfusion reactions]. PMID- 2197617 TI - [Destructive spondylodiskopathy in beta 2 microglobulin-induced amyloidosis]. PMID- 2197618 TI - [Localized peritoneal mesotheliomas. Report of a fibrous peritoneal mesothelioma (localized fibrous tumor) and 2 multicystic mesotheliomas]. PMID- 2197619 TI - [Intratesticular papillary cystadenoma. A rare analogue of serous papillary cystadenoma of the ovary]. PMID- 2197620 TI - Methodology and evaluation of dietary factors in Japan. PMID- 2197621 TI - Roles of micronutrients in cancer prevention: recent evidence from the laboratory. AB - In addition to differences in needs for dietary quality and quantity, humans, as individuals and as subsets of the population, are exposed to variations in climate, stress, environmental contaminants and other confounding factors which likely impinge on susceptibility to cancer. Despite the complexity of lifestyles and dietary habits, it is impressive to review available data on the relation of nutrients to cancer. There is sufficient parallelism between controlled animal studies and human behavior that we are compelled to believe that a variety of essential nutrients can modify carcinogenesis in humans and in lower animals. The micronutrients which appear to meet criteria for classifying them as protective agents in animal models include vitamin A and some of the synthetic retinoids; beta carotene; folic acid; vitamin C; choline/methionine; zinc, and selenium. Some of the others have suggestive effects but in the view of this author, the data are often equivocal, inadequate, or conflicting. These observations clearly support the proposal that animal studies have made enormous contributions in the past 15-20 years to our understanding of carcinogenesis and that this will continue into the future. From the data now available we can state with confidence that animal studies have shown that nutrients can modify the carcinogenesis process at specific sites and through a variety of mechanisms. These include effects on the formation of carcinogens from precursors; effects on metabolism of the carcinogen; effects on one or more stages of initiation, promotion, and progression; host defense mechanisms; cellular differentiation and on growth and metastasis of the tumor. The tools of the molecular biology, just now emerging in the field of nutrition, should have an immense impact on determining more accurately where nutrients exert their effects, how this is accomplished, and to suggest appropriate prevention and intervention techniques. Using molecular biology, combined with traditional and newer methods of toxicology and pathology, we should be able within a few years to better understand carcinogenesis and with such knowledge in hand to make sound recommendations about dietary habits to the public. PMID- 2197622 TI - The place of chemoprevention studies in cancer prevention planning. PMID- 2197623 TI - Epidemiologic studies of diet and cancer. AB - Prospective cohort studies conducted within the U.S., including older cohorts established to investigate causes of cardiovascular disease as well as newer cohorts designed to address hypotheses related cancer risk, have already contributed to our understanding of the relation of diet and cancer. During the coming years, however, a much greater wealth of data will emerge from the cohorts that have been initiated within the past decade. The principle strength of these studies is that they will provide an assessment of diet unbiased by the diagnosis of cancer. In addition, the cohort studies provide an assessment of diet closer to the actual onset of cancer. Importantly, validation studies have been conducted of the dietary questionnaires used in several of these studies, thus allowing a quantitative evaluation of the influence of measurement error on the observed measures of association and their confidence intervals. PMID- 2197624 TI - Linkage of serum sample bank and cancer registry in epidemiological studies. PMID- 2197625 TI - The IARC program of prospective studies on nutrition and cancer. PMID- 2197626 TI - Feasibility and importance of clinical trials of a low fat diet to reduce cancer risk. PMID- 2197627 TI - Time trends and international geographic variations related to diet and cancer. PMID- 2197628 TI - The feasibility of testing experimentally the dietary fat-breast cancer hypothesis. PMID- 2197629 TI - The American Cancer Society's strategic plan for dietary change. PMID- 2197630 TI - Implications of recent Australian epidemiological studies for cancer prevention through dietary change. PMID- 2197631 TI - Diet and cancer: methodological complexities and case-control studies in Greece. AB - Some methodological difficulties of epidemiological studies exploring the role of diet in the etiology of human cancer are considered and suggested corrective approaches are discussed. The advantages and disadvantages of case-control studies in this field are critically examined. The results and implications of several such studies undertaken in Greece are reviewed. PMID- 2197632 TI - Retrospective studies of diet and cancer at Roswell Park Memorial Institute. PMID- 2197633 TI - Retrospective studies of diet and cancer in Denmark. PMID- 2197634 TI - Diet and nasopharyngeal carcinoma. AB - Nasopharyngeal carcinoma (NPC) is a disease with a remarkable racial and geographical distribution. It is very rare (incidence of less than 1 per 100,000 person-years) in most parts of the world and only a handful of populations are known to deviate from this low-risk profile, which include people of southern China, Eskimos and other natives of the Arctic region, natives of southeast Asia, and the mainly Arab populations of north Africa and Kuwait. There is now convincing evidence implicating dietary factors as the primary cause of NPC among Chinese. A series of case-control studies conducted in various Chinese populations with distinct risks of NPC, ranging from the very high-risk Cantonese to the relatively low-risk Northern Chinese, have suggested that ingestion of salted fish and other kinds of preserved foods by the Chinese constitutes the most important cause of NPC development among these people. Preliminary data on Malays in southeast Asia, Eskimos in Alaska, and Arabs of north Africa also suggest that ingestion of preserved foods by these population groups may be responsible for their raised incidence of NPC. Regardless of race and geography, the commonest form of nasopharyngeal cancers are those that arise from the epithelial cells lining the nasopharynx. These carcinomas (commonly referred to as NPCs) constitute 75-95% of nasopharyngeal cancers in low-risk populations and virtually all nasopharyngeal cancers in high-risk populations (Ho, 1971; Sugano et al, 1978; Levine and Connelly, 1985). PMID- 2197635 TI - Efficacy of xantinolnicotinate in patients with dementia. AB - Activation of cerebral metabolism and improvement of microcirculation by influencing rheological parameters are claimed to be the underlying pharmacological principles responsible for the efficacy of xantinolnicotinate. This dual mechanism of action led the authors to perform a double-blind, randomized, placebo-controlled study in patients with mild to moderate dementia (DSM III), characterized by a score of 40-90 on the Sandoz Clinical Geriatric Scale (SCAG), with a separate randomization for patients with Multi-Infarct Dementia (MID) and Senile Dementia of Alzheimer Type (SDAT). It was calculated that 150 patients would have to be recruited for each group. Allocation to the respective group (MID or SDAT) was based on the Hachinski Ischemic Score and computer tomogram. Preceded by a 2-week placebo run-in period, a 12-week treatment period followed with either 3 x 1 g xantinolnicotinate (Complamin) or placebo. Prior to the study, the physician's rating of the global therapeutic effect from the clinical global impression (CGI) was designated as the primary criterion of efficacy. Secondary efficacy criteria were SCAG, the BGP nursing rating, and, as psychometric variables, tests from the Nuremberg Psychogeriatric Inventory (NAI). The improvement compared to placebo was statistically significant for the CGI in both treatment groups (p less than 0.0001) and hence independent of etiology. Concerning the nurses' rating (BGP), apart from a marginally statistically significant difference for the factor "need of help" in the SDAT group, no remarkable changes were registered during treatment. However, in the SCAG the differences between verum and placebo were significant (MID p less than 0.0002; SDAT p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2197636 TI - ICD-10 field trial in German-speaking countries. PMID- 2197637 TI - Chapter V (F) of ICD-10: mental, behavioural and developmental disorders- introduction and overview. AB - The need for precise psychiatric diagnoses is indisputable, both for cooperation within the health service systems and for scientific purposes. Over the last few years there has been a revival of interest in psychiatric nosology. Despite new strategies and the results of numerous individual research efforts, no uniform and general satisfactory theory, and thus no classification of mental disorders, has been developed. After the Second World War, the WHO succeeded in introducing an internationally accepted diagnostic system, the ICD-classification. In 1980 the American Psychiatric Association (APA) introduced its DSM-III classification with explicit diagnostic criteria and rules. The ICD-10 has been in preparation since 1982, and will differ considerably from ICD-9: An alpha-numerical system of coding expands the possibilities for diagnoses. For the first time in the history of ICD operational diagnostic criteria and rules are being introduced. The new structure will permit adjustments without the need to completely change the entire classification. The WHO division of mental health is preparing a range of documents and instruments for various purposes; clinical descriptions and diagnostic guidelines for daily clinical use, a short version and the more detailed research criteria; a multiaxial coding is planned as well. The classification of the mental disorders is based on etiological considerations, as far as these are known, in particular in the case of organic disorders, disorders due to the use of psychoactive substances, and stress-related disorders. In other areas, a more non-theoretical and descriptive approach was chosen. As a major change the large "blocks" psychoses and neuroses have been abandoned.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2197638 TI - Design of the ICD-10 field trial in German-speaking countries. AB - The study design of the international multicentric field trial on ICD-10, chapter V (F) "Mental, Behavioural and Developmental Disorders: Clinical Descriptions and Diagnostic Guidelines" (1987 draft) including some modifications for the study in German-speaking countries, is described. The various stages of the field trial, instruments used, and the data base, are presented. PMID- 2197639 TI - Organic, including symptomatic, mental disorders (section F0)--results of the ICD 10 field trial. AB - The natural history of classification systems for the organic mental disorders from ICD-8 through ICD-10 and DSM-III is presented. Out of a total of 31 cases the 6 with a main diagnosis of the F0-section of ICD-10 are described and field trial results analysed in terms of classification errors, goodness of fit, difficulty, and interrater-reliability. Specific categories (instead of "collective categories") were used more frequently and fewer classification errors made on the basis of ICD-10 as compared with ICD-9. The authors suggest that an operationalized differentiation of dementia as one of the core categories would further increase the reliability and clinical practicability of this section. PMID- 2197640 TI - Mental and behavioural disorders due to psychoactive substance use (section F1): results of the ICD-10 field trial. AB - The ICD-10 field trial of section F1 (mental and behavioural disorders due to psychoactive substance use) shows comparatively high acceptance of the new classification in German-speaking countries. Goodness of fit and subjective confidence of the main diagnosis are above average. Analysis of interrater reliability with regard to main diagnostic categories reveal certain problems. The reliability values are flow average within the ICD-10 field study. Possible causes for low interrater reliability are inadequate differentiation from section F0 (organic disorders) and uncertainties in the differential assessment of psychopathological symptoms between F1 and F2, as also between F1 and F4. Interrater reliability could be improved by introducing "psychoactive substance use" as a separate axis in a forthcoming multiaxial scheme for ICD-10. PMID- 2197641 TI - Schizophrenia, schizotypal and delusional disorders (section F2): results of the ICD-10 field trial. AB - To determine whether the use of ICD-10 provides greater diagnostic reliability than ICD-9, a field trial of the ICD-10 draft (WHO, 1987) was carried out. A total of 1,778 diagnoses made on the basis of ICD-10, ICD-9 and, in part, DSM-III were established by 134 clinicians in 10 centres using case reports and interviews. The corrected reliability coefficients of schizophrenic disorders obtained with ICD-10, with kappa-coefficients of reliability of 0.69 for the 2 character category and 0.67 for the 3-character category are higher than those reported for the diagnosis of schizophrenia made without specified criteria, but lower than those reported for DSM-III. Despite the operationally defined diagnostic guidelines, diagnostic discrepancies still persist when organic disturbances, substance abuse or psychogenic features are additionally present. The diagnoses of each rater remain stable on change over from ICD-9 to ICD-10. Our data suggest that ICD-10 is suitable for worldwide use in diagnosing schizophrenia. PMID- 2197642 TI - Neurotic, stress-related and somatoform disorders (section F4) and physiological dysfunction associated with mental or behavioural factors (section F5): results of the ICD-10 field trial. AB - The results of the ICD-10 field trial in German-speaking countries relevant to sections F4 (neurotic, stress-related and somatoform disorders) and F5 (physiological dysfunction associated with mental or behavioural factors) show a comparatively low level of acceptance. Interrater-reliability in various diagnostic categories is not always adequate. In particular the allocation of some of the "old" diagnostic entities of ICD-9 to various sections of ICD-10, and in part unsatisfactory classificatory distinctions gave rise to certain problems. PMID- 2197643 TI - Abnormalities of adult personality and behaviour (section F 6)--results of the ICD-10 field trial. AB - Personality disorders, the most important category of section F6, were studied in the ICD-10 field trial. The overall Kappa values for interrater reliability of section F6 is 0.64, for personality disorders 0.61 and for dyssocial personality 0.73. These results are very close to those of the DSM-III field trials. Subjective assessments of feasibility, suitability and goodness of fit demonstrate good acceptance of the diagnostic guidelines by the clinicians. A comparison of ICD-9, DSM-III and ICD-10 diagnoses yielded broad agreement for diagnoses of personality disorders with overlapping Kappa values of 0.91 and 0.94. The acceptance and reliability of the new classification could be increased by a number of improvements and the planned introduction of a multiaxial system. PMID- 2197644 TI - Psychiatric disorders in children and adolescents: results of the ICD-10 field trial. AB - Of the numerous changes made in the classification of psychiatric disorders in children and adolescents in ICD-10 the most important are described. In an evaluation of the revised scheme, 7 raters from 2 facilities classified 40 case histories with both ICD-10 and ICD-9 codes. For ICD-10 and 4 character codes the level of agreement was 56% (ICD-9: 60%). As expected, 3-character codes yielded better agreement (ICD-10: 71%; ICD-9: 72%). Within-facility agreement was roughly the same for each. The lowest levels of agreement for a given category were for mixed disorders of conduct and emotions (F92) and depressive disorders (F31, F43). The reasons for this are discussed. PMID- 2197645 TI - Phenomenal and operationalized classification of psychiatric disorders in children and adolescents with ICD-9 and ICD-10, on the basis of a field study. AB - In connection with the implementation of ICD-10, a further multicenter field study was conducted with 33 raters from 9 facilities for child and adolescent psychiatry. Each rater evaluated the same 29 case studies, resulting in a total of 957 ratings. When coding was done with 4-character ICD-10 codes interrater agreement on a given diagnosis averaged 50.3% (ICD-9: 47.3%); with 3-character ICD-10 codes the figure was 61.0% (ICD-9: 66.5%). When alternative diagnoses were also considered, agreement improved by about 7% (4-character codes) and 7.4% (3 digit codes), respectively. The highest levels of agreement were found for monosymptomatic disorders (F94, F95 and F98), the lowest for mixed disorders of conduct and emotions (F92) and depressive disorders (F31, F43). These results indicate that, on the whole, psychiatric disorders in children and adolescents can be classified reliably with the ICD-10, even when the raters have had no experience with the scheme. PMID- 2197646 TI - Comparison of the ICD-10-classification with the ICD-9- and the DSM-III classification of mental disorders. AB - The diagnostic concepts in ICD-10 show better congruence with those in DSM-III than with those in ICD-9. The diagnostic definitions used by ICD-10 and DSM-III for the majority of diagnoses turn out to be similar; the definitions of anxiety disorders and schizoaffective disorders are, however, still at variance. Consequently, the empirical results from the WHO field trial in German-speaking countries reveal a high degree of overlap between the two systems; the degree of overlap between ICD-9 and ICD-10 was lower, but still surprisingly high overall. These empirical results support the validity of ICD-10. PMID- 2197647 TI - Feasibility, suitability, and interrater reliability of ICD-10 during different stages of the ICD-10 field trial. AB - A total of 134 clinicians in 10 centres participated in the WHO-initiated field trial in German-speaking countries prior to the introduction of ICD-10 (chapter V; categories F00-F99. Mental, Behavioural, and Developmental Disorders), and provided 1,778 diagnostic assessments of 90 cases. Since these assessments were made in different phases of the field trial, the present study investigated how the "feasibility" and "suitability" of the so-called "Clinical Descriptions and Diagnostic Guidelines" was assessed within the individual phases. In addition, the interrater reliability of diagnostic assessments for the respective phases was investigated. The results show that ICD-10 was accepted both at the beginning of the study, and after several months of use. With respect to interrater reliability, improvements in some of the categories are necessary. PMID- 2197648 TI - ICD-10 field trial in German-speaking countries--summary of the quantitative empirical results. AB - The summary of the quantitative results of the ICD-10 field trial in German speaking countries shows a adequate acceptance of ICD-10. The figures for interrater reliability for the diagnostic categories are adequate for most categories considering the comparatively low level of familiarity with the new system. The high degree of overlap between the diagnostic categories in ICD-9 and ICD-10 is an indication of the validity of ICD-10. The major source of disagreement is the relocation of several diagnostic categories to different sections. PMID- 2197649 TI - Summary of the qualitative criticisms made during the ICD-10 field trial and remarks on the German translation of ICD-10. AB - The 1987 draft of ICD-10 presents many new aspects of the psychiatric diagnostic evaluation. Some were readily accepted by the participants of the field study, including: the purely descriptive approach with the abautonment of many theoretical concepts; the more operationalized descriptions of the diagnoses; similarity in structure and terms to DSM-III-R. Others proved controversial: extension of the term dementia to include even mild and moderately severe organic psychosyndromes; inclusion of all forms of depression in one chapter, and their subdivisioning only by severity; different time criteria for the diagnosis of schizophrenia in DSM-III-R (6 months) and ICD-10 (1 month). Considerable criticism was levelled at the overly long and often tediously formulated text, and the lack of didactic organisation. A number of examples of translation difficulties are given, and the differences between a too literal and a technically correct equivalent translation disu-used. PMID- 2197650 TI - ICD-10 field trial in German-speaking countries--summary, judgement and perspectives. AB - On the basis of the results of the field trial, the most important classificatory innovations of ICD-10, together with their advantages and disadvantages are described. The initial good acceptance of the new system could be further improved by structural modifications, such as a uniform and systematic description of the individual diagnostic categories. Criticism of content was focused on affective and neurotic disorders and adult personality disorders. When it is introduced, the psychiatric chapter of ICD-10 will surpass most of the hitherto existing psychiatric classification systems in size, differentiation and international testing. PMID- 2197651 TI - Metaliteral dreaming: a right hemisphere dominant linguistic activity. AB - Many dream reports, which take the form of propositional speech, are more meaningful if understood as metaliteral speech. To achieve this understanding the speech sounds must be decoded according to different linguistic rules than govern propositional speech. The basic rules for metaliteral speech were outlined in a recent paper. Those rules came from empirical observation. This paper proposes that the right hemisphere is dominant for the linguistic activity of metaliteral speech because, in one way or another, the rules all seem to depend on the cognitive use of right hemisphere functions, or sometimes, on the absence of left hemisphere functions. The proposed theory rejects an exclusive role for the right hemisphere in metaliteral behavior. By recognizing the subordinate role of the left, the puzzles are solved of the story-like quality to dream reports and the central role of prosody in decoding metaliteral speech. PMID- 2197652 TI - Our unacknowledged ancestors: dream theorists of antiquity, the middle ages, and the renaissance. AB - Exploring the dream world from a modern, or post-modern, perspective, especially through the lens of contemporary technologies, often leads us as researchers to see ourselves as engaged in a new and revolutionary discourse. In fact, this self image is a profoundly ahistorical one, because it ignores the contributions of ancient, medieval and Renaissance oneirologists who wrote extensively, albeit in different terms and images of lucidity, prerecognition, day residue, wish fulfillment, incubation, problem solving, REM, obe, and the collective unconscious. There are also analogues in these early accounts to anxiety, recurrent, mirror, telepathic, shared, flying, and death dreams. Dream interpretation through music, analysis of dream as narrative, sophisticated theories about memory and language and symbolization are all part of the tradition. Further, early texts pose many issues in sleep and dream research which are not currently being pursued. We dream workers of the late twentieth century should therefore fortify ourselves with knowledge of the oneiric past as one important way to enhance our dream work in the twenty-first century. PMID- 2197653 TI - A clinical view of mandibular premolars in removable partial denture design. AB - Mandibular premolars are used as a model to discuss various strategies for the design of removable partial dentures. Factors that must be taken into consideration as the prosthesis is designed, such as coronal and radicular anatomy of the abutment teeth, the relationship of the abutment teeth to other teeth, and the presence of existing restorations, are also identified. PMID- 2197654 TI - In vitro study on the inhibiting effect of different agents on the growth of Candida albicans on acrylic resin surfaces. AB - This study evaluated at the in vitro level the antifungal effectiveness of nystatin, chlorhexidine, and a homologous histidine polypeptide on the surface of acrylic resin disks. The agents were used in a way that simulated storage of a denture by a denture wearer. Results indicated that pretreatment with poly-L histidine was not protective against C albicans adherence and growth regardless of whether disks were stored in water or in the open air for the 8-hour period following yeast contamination. Chlorhexidine was totally effective in preventing C albicans attachment to, and growth on, the acrylic resin, even after a period of 8 days of turbidimetric monitoring. Pretreatment with Nystatin, followed by drying, was protective, yielding results similar to those obtained with chlorhexidine. PMID- 2197655 TI - Evaluation of a dental unit designed to prevent retraction of oral fluids. AB - Most older units that drive high-speed dental handpieces include a retraction device designed to prevent dripping of fluids from the water-spray line after the unit has been turned off. Oral fluids and debris may be drawn, along with water, into the water line. Bacteria and debris, unless deliberately flushed out of the water line, may be transmitted to the next patient. Most new units now have mechanisms to prevent retraction. A new dental control unit, designed to eliminate mechanical aspiration of oral fluids, was tested. A kit to test the level of retraction in the water-spray line was also examined. The new unit was found to be effective in protecting the unit water from contamination by oral microorganisms, thereby protecting patients from cross-contamination. However, the control of retraction did not prevent the colonization of the water line by aquatic bacteria. Both internal and external sources of microorganisms must be controlled. PMID- 2197656 TI - An esthetic, bonded inlay/onlay technique for posterior teeth. AB - In the past, the primary focus of dentistry has been on the alleviation of pain and stopping the progression of disease. The reduction in the prevalence of dental caries, along with advances in adhesive technology, have combined to revolutionize the practice of dentistry today. The modern dentist, using the latest available cosmetic techniques, is now able to satisfy the emotional wants and needs of patients. The public, well informed about the possibilities for anterior esthetics, now desire tooth-colored restorations in the posterior. A new heat- and pressure-curing resin inlay/onlay material and the clinical and laboratory technique for its use are discussed. PMID- 2197657 TI - The use of the splint bar in conjunction with removable partial denture treatment. AB - The use of a bar, joined to lone-standing abutment teeth, that spans an edentulous space is an important treatment option for many partially edentulous situations. The splint bar provides positive vertical support for the removable partial denture while rigidly splinting the abutment teeth. This article defines the situations in which this treatment should be considered and describes the technique to achieve a successful result. PMID- 2197658 TI - A 12-year clinical evaluation of two composite resins. AB - Two composite resin materials were clinically evaluated after 12 years in vivo. Although the Class III restorations did not have the benefit of acid etching and bevels, all 32 restorations in the nine patients who were located were intact, and none needed to be replaced. Stain was the most prominent problem, both at the margins and on the surface of the restorations. Neither wear or marginal integrity appeared to be a problem. PMID- 2197659 TI - Microleakage and marginal placement of a glass-ionomer liner. AB - Glass-ionomer cements, with their ability to bond to dentin, have been reported to produce less microleakage than several other restorative resin materials. This matched-pair study reports the effect on microleakage of placement of a light curing glass-ionomer cement used as a liner when extended out to the dentinal cervical cavosurface margin or held short of that margin. Pairs of circular Class V cavities involving 50% enamel, with bevel, and 50% cementum were cut in 31 extracted third molars. After placement of the glass-ionomer cement, etching of the bevel, and placement of a resin bonding system, microfilled resin was placed over the bonding agent in one increment, light-cured, finished, and given 500 thermocycled 500 times between 5 and 55 degrees C. A silver nitrate staining technique was used to evaluate microleakage measured in graticular units (gu) along the dentinal interface under stereomicroscopy. The extension of the glass ionomer liner out to the dentinal cavosurface margin did not significantly improve microleakage performance compared to performance of the liner when it was placed short of that margin and covered by a resin veneer. From other considerations, such as the potential for mechanical breakdown of the glass ionomer cement when exposed to the oral environment and abrasion, and the possibility for improved esthetics, the clinician should consider holding the glass-ionomer liner short of the dentinal cavosurface margin and covering it with a composite resin veneer of a thickness consistent with structural integrity. PMID- 2197660 TI - Inflammatory papillary hyperplasia: review of literature and case report involving a 10-year-old child. AB - Inflammatory papillary hyperplasia is a benign lesion of the palate seen most often in patients with a history of ill-fitting dentures or poor oral hygiene. The specific cause is unknown. Inflammatory papillary hyperplasia can occur at any age. However, it is most often seen in patients in the third to fifth decades. It occurs more frequently in males and whites. The best treatment is surgical removal. The prognosis is excellent, once the lesion is removed. The patient presented in this case report is a 10-year-old black girl without a history of a dental prosthesis. It is conjectured that poor oral hygiene and a habit of mouth breathing contributed to the occurrence of inflammatory papillary hyperplasia in this patient. The lesion was surgically removed, and the patient was followed up for a period of 18 months without recurrence of the lesion. PMID- 2197661 TI - Oral ulcerations. AB - Ulcerations are common occurrences in the mouth. Causes include physical trauma, radiation, chemical injury, and microbial infection (bacterial, viral, and fungal). Some ulcerations, such as recurrent aphthous stomatitis, Behcet's syndrome, and erythema multiforme, are of uncertain etiology, whereas others (eg, pemphigus, pemphigoid) are apparently of immunologic origin. Malignant neoplasms also may present as ulcerations. Because the natural history and treatment varies with the diagnosis, the practitioner should become familiar with the clinical appearance of the various types of ulcerations so that appropriate treatment can be instituted. PMID- 2197662 TI - Bonded composite resin crowns for primary incisors: technique update. AB - A technique for restoration of carious primary maxillary incisors with a hybrid visible light-curing composite resin and a dentinal bonding agent is described. Careful use of this technique and the new materials can provide a restoration that is esthetic and resistant to fracture and displacement. The technique requires careful preparation of the operative field and precise handling of the restorative materials. The method is illustrated by the placement of bonded composite resin crowns in a 3-year-old boy. PMID- 2197663 TI - An alternative hypothesis to the cause of pulpal inflammation in teeth treated with phosphoric acid on the dentin. AB - This paper explores the possibility that the inflammatory response in pulpal tissues noted in some early studies when dentin was treated with phosphoric acid was not caused by the acid. It suggests that the inflammatory response was caused by the prolonged exposure to zinc oxide-eugenol and documents many reports that show ZOE to be a relatively toxic material. The paper also suggests that biocompatibility studies as performed today may be inappropriate. PMID- 2197664 TI - The effect of etching on the dentin of the clinical cavity floor. AB - The most conservative cavity preparation, which takes full advantage of chemically adhesive composite resin, involves removal of only the infected outer carious dentin that is stainable by the caries detector. This preparation exposes in the cavity floor either the turbid layer at the top of the inner carious dentin or the underlying transparent layer. Examination by scanning electron microscope revealed that etching the cavity floor demineralized the intertubular dentinal surface slightly and produced tapered, cylindrical holes or ring-shaped holes at the dentinal tubule apertures of the turbid or transparent layer, respectively. The holes were blind with solid floors of intratubular crystal deposits of the transparent layer, suggesting that etching increases permeability little. Placement of the adhesive resin on the etched cavity floors produced a resin-impregnated dentinal layer and tapered, cylindrical or tubular-shaped resin tags, which apparently improved the bond and tubule aperture seal. PMID- 2197665 TI - Esthetics with glass-ionomer cements and the "sandwich" technique. AB - The Type II restorative esthetic glass-ionomer cement has not been generally regarded as a useful esthetic restorative. However, as long as its relatively slow-setting chemistry is understood and accepted and provision is made to maintain the water balance for the first 24 hours, it can be just as useful as composite resin. Taking into account the fluoride release, its tissue compatibility, and the chemical union with underlying tooth structure that is available, it is suggested that it has a valuable place in restorative routines. Manufacturers have been encouraged recently to try to produce a fast-setting cement that can be polished at the insertion appointment. A varnish to seal newly placed restorations is supplied by most manufacturers, but these are not completely waterproof. A low-viscosity, single-component, light-activated resin bonding agent has been shown to work satisfactorily as a sealant, and, with its use, it is possible to develop adequate translucency and optimal physical properties in the oral cavity. PMID- 2197666 TI - Improving the adaptation of denture bases by anchorage to the casts: a comparative study. AB - The purpose of this study was to investigate the adaptation of complete maxillary dentures to stone casts processed by the conventional, and two anchoring, methods. The anchoring methods used holes drilled on the cast and a special flange extended onto the posterior aspect of the maxillary cast. Both anchoring methods improved the adaptation of denture bases by minimizing the discrepancy between the denture base and cast. The greatest discrepancies observed in all methods were at the central portion of the posterior border. PMID- 2197667 TI - Effects of smoking and/or vitamin C on crevicular fluid flow in clinically healthy gingiva. AB - The purpose of this study was to (1) compare crevicular fluid flow in smokers and nonsmokers with clinically healthy gingiva; (2) compare crevicular fluid flow of smokers in the areas physically exposed to smoke (maxillary lingual) to that in areas not physically exposed to smoke (maxillary buccal); and (3) compare crevicular fluid flow in smokers and nonsmokers before and after 1 month of (500 mg) twice daily vitamin C supplementation. All sampled areas were required to exhibit clinical health for all measurements (gingival, plaque, and bleeding indices at 0). Ten smoking (at least one pack a day) and ten nonsmoking male dental students were subjects of the study. Areas sampled were midbuccal and midlingual of teeth 3, 5, 12, and 14. Smokers were found to have significantly less crevicular fluid flow than did nonsmokers. Lingual areas of smokers showed no significant difference from buccal areas in crevicular fluid flow. One month of (500 mg) twice daily vitamin C supplementation resulted in a significant decrease in crevicular fluid flow in smokers and nonsmokers. The effect of tobacco smoke on clinically healthy gingiva may be a physiologic result of vasoconstriction rather than a physical irritation. PMID- 2197668 TI - Retentive strength of six temporary dental cements. AB - The retentive strength of three zinc oxide-eugenol cements and three noneugenol containing zinc oxide cements and the effect of the addition of petrolatum on retention were tested. The addition of petrolatum was found to affect retention of the cements significantly. Retention strengths varied from 1.6 kg to 40.0 kg. Of the Class 1, Type 2, systems tested, noneugenol cements had higher retentive values than did the eugenol-containing cements. PMID- 2197669 TI - Avoidance of cast breakage during removal from the impression. AB - Breakage of a dental cast during its removal from the impression may result in inaccuracies in the finished appliance. The origin and prevention of the factors that can lead to cast breakage are found in the diagnostic phase. Casts of isolated teeth that are long, have marked gingival recession, and have a narrow clinical neck are prone to fracture. If casts of these types of teeth cannot be avoided, measures can be taken to prevent fracture. Wax can be used to thicken teeth with narrow clinical necks or to block out interproximal spaces in adjacent teeth without proximal contacts. The materials used to make the impressions and casts should also be chosen carefully. Methods of removing the cast to avoid fracture include the use of a soldering iron to cut the tray. Once the tray is sectioned, the impression material is free to elongate, and the cast can be removed easily. PMID- 2197670 TI - RLS--the lingually retained clasp assembly for distal extension removable partial dentures. AB - The design of clasp for a distal extension removable partial denture that helps preserve both the abutment teeth and the tissues of the edentulous ridge is described. The clasp assembly takes advantage of surveyed lingual undercuts to provide support, retention, and stability. It consists of a mesio-occlusal rest, a distolingual L-bar direct retainer that is located on the abutment tooth adjacent to the residual ridge, and a distobuccal stabilizer (RLS). PMID- 2197671 TI - Reversible agar agar hydrocolloid. AB - Reversible agar agar hydrocolloid remains an excellent, cost-effective impression material. A review of the history of the development of the material and a sound technique for its use are presented. PMID- 2197672 TI - [Molecular mechanisms of SOS response of E. coli]. PMID- 2197673 TI - [Herpes simplex virus: molecular basis of replication and pathogenesis]. PMID- 2197674 TI - [Transcriptional regulation of major histocompatibility complex class I gene]. PMID- 2197675 TI - [Regulation of phosphatidylcholine (phosphatidylethanolamine) biosynthesis in animal cells]. PMID- 2197676 TI - [Transport proteins for drugs and bile acids in the liver cytosol and plasma membrane--its multiplicity and functions]. PMID- 2197677 TI - [Production of recombinant proteins using baculovirus]. PMID- 2197678 TI - [Structure and reaction mechanism of ribozyme]. PMID- 2197679 TI - A critical review of visual analogue scales in the measurement of clinical phenomena. AB - Visual analogue scales (VAS) have been used in the social and behavioral sciences to measure a variety of subjective phenomena. The VAS method has potential utility for the measurement of a variety of clinical phenomena of interest to nurse investigators. In this review a description of the various forms of the VAS and an historical overview of their development are presented. In addition, conceptual, psychometric, and statistical aspects of the VAS are considered. Finally, strengths and limitations of the VAS method are addressed. PMID- 2197680 TI - [Prevention of post-transfusional malaria in France: a descriptive survey]. AB - Due to an expansion in international travel, an increasing number of blood donors are at risk of exposure to malaria. Preventions of transfusional malaria is required by law in France. Acting as National Reference Center for Malarial Immunology we noticed that this regulation was not being respected by all blood banks. We conducted a questionnaire study concerning 181 blood banks to evaluate under which circumstances serological tests were requested, the policy employed in case of seropositivity, the cost of screening, and wishes concerning modification of the law. The response rate was 46.9%. We noticed a great variability in attitude: only 21% of blood banks followed the regulation; 63% added extra criteria to the law; 16% did not follow the regulation. Indirect immunofluorescence was the main method used by 91.5% of blood banks. However the specificity threshold fluctuated. The fate of the blood unit in case of seropositivity was variable (discard of blood bags, plasma fractionation, blood used). Centers who answered to questionnaire performed 2,513,687 blood donations during the survey. A serology was carried out in 2.6% of donations, and was positive in 9.4% of cases i.e. 0.24% of donations. The average cost of screening was 35 FF. The profit loss due to discard of positive blood was estimated at 1.7 million FF. for the duration of the survey and the blood banks studied. 99% of centers answering the questionnaire expressed desire for standardisation of screening method. PMID- 2197681 TI - [A study of various smoking cessation programs based on close to 1000 volunteers recruited from the general population: 1-month results]. AB - The harmful effect of tobacco on health is well known. To help smokers to stop smoking, a study was designed in 1987 to assess the efficacy of two treatments and the advantage of combining them. The treatments, nicotine chewing gum and acupuncture, were randomly allocated. The 996 subjects required are now included. The characteristics of the participants, the number of nicotine gums used as well as the need for a cigarette are described. Cessation rates in the four groups, one month after the beginning of the treatment, differed significantly (p less than 5%). The efficacy of acupuncture was not shown (abstinence rates of 22 and 23% for the active and placebo groups respectively), whereas the efficacy of nicotine gum was (26 and 19% for the active and placebo groups respectively). The interest of the association of the two treatments was not observed. PMID- 2197682 TI - Review of randomized trials of homoeopathy. AB - The present review covers forty published randomized trials in which the results of a homoeopathic treatment were compared to those of a standard treatment, a placebo, or no treatment at all. These trials were identified after an extensive search through the literature. They cover a wide range of pathologies. Most were double-blind and used subjective and/or multiple endpoints. The median number of patients per group was 28. The analysis only included all the randomized patients in one third of the trials. In our opinion, the results do not provide acceptable evidence that homoeopathic treatments are effective. PMID- 2197683 TI - The use of sleep studies in neurologic practice. AB - Polysomnographic studies have been shown to be useful in the diagnosis of many sleep disorders, particularly those associated with impaired respiration during sleep or impairment of daytime alertness. As with any test, unless it is performed under ideal conditions, the amount of information obtained may be limited. Because of the interaction between nighttime sleep and daytime alertness, disorders associated with impaired alertness usually require at least 24-hour assessment. The polysomnogram and MSLT, although detailed and time consuming, are essential for the accurate diagnosis of many sleep disorders. If a primary sleep disorder is suspected, polysomnographic testing, particularly early in the patient's evaluation, may obviate unnecessary neurologic and medical tests, which yield little information in the assessment of disorders of sleep and wakefulness. PMID- 2197684 TI - Ambulatory polysomnography in the study of patients with disorders of initiating and maintaining sleep. AB - We have presented the rationale, treatment implications, and recording and data reducing techniques of ambulatory PSG. We find the method well accepted by patients, the data of adequate quality, the scoring of tape-recorded data far easier than with paper recorded data, and the interpretations of value in the diagnosis and treatment of patients presenting with DIMS. PMID- 2197685 TI - Electromyography and nerve conduction laboratory in clinical neurologic practice. PMID- 2197686 TI - Neurophysiologic monitoring during surgery of peripheral and cranial nerves, and in selective dorsal rhizotomy. AB - Physiologic monitoring may warn of impending neural damage and intraoperative assessment may provide critical information used to direct the surgical procedure itself. Intraoperative techniques utilize methods modified from the diagnostic neurophysiologic laboratory. Simultaneous multimodality recording of different signal sources is of particular value for several types of procedures. Intraoperative studies must be tailored to each patient's clinical condition and to the specific surgical risks. Since studies have supported the benefits of intraoperative monitoring for peripheral nerve and cranial nerve surgery, monitoring is not likely to be subjected to the rigors of a randomized controlled study for these procedures. PMID- 2197687 TI - The role of the electroencephalogram in neurologic practice. PMID- 2197688 TI - EEG topographic mapping and frequency analysis: techniques and studies in clinical setting. PMID- 2197689 TI - Paperless electroencephalography. AB - "Paperless EEG" incorporates a variety of techniques for recording, storing, reformatting, transmitting, and analyzing EEG records. The general advance in microelectronics has provided the EEG community with this collection of options. Many of these will come to be commonplace in the EEG laboratory of the future, and indeed some of these are making inroads into EEG practice. Storage of EEG may be the simplest area in which these tools can be used at present, and they may be cost-effective for many laboratories even now. Other features offer ways to improve the EEG product, including the ability to change the filters, paper speed, and montage after the recording has been made. In these ways, even reading of the traditional polygraph EEG can be enhanced by paperless tools. Some other tools are still under development or are best used at specialty centers. Methods of artifact removal, event detectors, and spike detectors still are not quite ready for routine use everywhere, but can now enhance EEG techniques in specific settings. As the field of EEG moves toward the 21st century, the impact of modern electronics should continue to encourage advances toward more widespread use of all of these tools. These advances should help to create an EEG that is cost competitive with existing services while providing a qualitatively better product. PMID- 2197690 TI - Clinical utility of event-related potentials in neurology and psychiatry. PMID- 2197691 TI - The electroretinogram in neurologic practice. AB - The ERG can be helpful to the neurologist who must evaluate patients with known or suspected retinal disease. The test is most useful in detecting (or excluding) outer retinal disease, especially in presymptomatic, very young, or mentally enfeebled patients. It can also help in interpreting the meaning of an abnormal VEP. PMID- 2197692 TI - Amo Amand/Amant. PMID- 2197693 TI - [Traumatic ossifying myositis]. PMID- 2197694 TI - [History of medicine. Poisons and pre-Columbian and traditional American Indian remedies]. PMID- 2197695 TI - [Entomology and legal medicine: origins, development, actualization]. PMID- 2197696 TI - Running shoes. Their relationship to running injuries. PMID- 2197697 TI - Athletic performance following rapid traversal of multiple time zones. A review. AB - Athletes travel across multiple time zones in order to engage in national or international competition. It has often been assumed that rapid transmeridian translocation has a negative impact on athletic performance. However, the available studies are characterised by major methodological problems. Consequently, no compelling evidence exists demonstrating that air travel adversely influences athletic performance. Evidence suggests that distance and sprint running performance, as well as dynamic muscular strength and endurance of the elbow flexors, is impaired following west-east travel across 6 times zones in untrained individuals. However, there is no evidence that these findings for untrained subjects generalise to athletes. Both physiological and psychological mechanisms might account for potential effects of travel on athletic performance, but little is known about these potential mechanisms with regards to athletic performance. Systematic research is needed if the relationship between air travel and athletic performance is to be elucidated. PMID- 2197698 TI - Applied physiology of squash. AB - Squash is a moderate- to high-intensity intermittent exercise. Players are active 50 to 70% of the playing time. 80% of the time, the ball is in play 10 seconds or less. The rest intervals fit a normal distribution with an average duration of 8 seconds. Heart rate increases rapidly in the first minutes of play and remains stable at approximately 160 beats/min for the whole match no matter what levels the players are. The energy expenditure for medium-skilled players is approximately 2850 kJ/h and over 3000 kJ/h for A grade players. The thermal and metabolic response to squash is similar to that of moderate intensity running. Hyperglycaemia, elevated free fatty acids and growth hormone levels, and low serum insulin values are the common metabolic changes. Blood lactate levels are understandably low due to the very short work to rest pattern of play. Injuries are not frequent in squash but they can occur. Serious eye injuries have been documented and as a result protective equipment is highly recommended. To reduce the possibility of sudden death on the court or after the game, older players that present some risk factors for cardiovascular disease should be warned against smoking after the game and informed of the serious implications of the development of chest pain, or undue tiredness before, during or after squash. PMID- 2197699 TI - Muscular atrophy following immobilisation. A review. AB - Muscular atrophy regularly occurs as a consequence of immobilisation or disuse after sports injuries. Several experimental models deal with muscle atrophy and are suitable for investigations of the underlying mechanisms of muscle atrophy. Strength loss is the most evident response to atrophy. Muscle strength decreases most dramatically during the first week of immobilisation; little further weakening occurs later on. This is reflected in changes in the EMG of disused muscles and can also be observed in muscle weight and size of muscle fibres. Slow muscles with predominantly oxidative metabolism are most susceptible to atrophy as indicated by various findings: slow muscle fibers show greater atrophy than fast fibres; their relative and probably absolute number is decreased in atrophic muscles; in addition, the oxidative enzyme content is most severely affected by disuse. Atrophic muscle is characterised by a catabolic metabolism. The rate of protein synthesis is reduced and that of protein breakdown increased. Autophagic activities probably play an important role in early stages of muscular atrophy. The oxygen supply to disused muscle may be impaired, although myoglobin content is increased in atrophic muscle. The complete loss of mitochondrial function during the first days of disuse may be of aetiological importance. The amount of connective tissue is increased in atrophic muscle and surrounding periarticular tissue which may lead into a vicious circle of musculoskeletal degeneration. An almost complete recovery from atrophy is possible, yet often the recovery phase is much longer than the total immobilisation period. PMID- 2197700 TI - Injuries in badminton. AB - Though badminton is one of the most widely played sports in the world, it has received little sports medical interest. Based on the few existing studies on injuries in badminton, compared to other sports it is of relatively low risk and dominated by overuse injuries. The injury duration is relatively long, but only a few working days are lost. Anatomically, most injuries are localised to the foot and ankle. The single most frequent injuries are Achilles tendinitis and tennis elbow. Rupture of the Achilles tendon is a rare injury, which is typically seen in older recreational players. When the time of exposure is taken into account men are found to have a higher injury risk than women, and recreational players a higher injury risk than elite players. In contrast to most other sports the relative injury risk is higher during training than in competition. Based on suggested causes of injury and injury mechanisms, together with the known injury pattern in badminton the following preventive matters are suggested: (a) changes in the badminton shoe, towards a higher heel, with shock absorption and a stiffer anatomically fitting heel counter; (b) adjustment of the friction between the individual shoe-soles and playing surfaces; and (c) specific badminton training including stretching and strengthening of the triceps surae and the muscles involved in the internal and external rotation of the shoulder and elbow during the badminton strokes. PMID- 2197701 TI - Epilepsy and sports. AB - Millions of healthy people participate in sport on a regular basis. Moreover, in the last decade patients with chronic disorders have been encouraged to take part in sporting activities as a part of their rehabilitation. Can epileptic patients freely participate in sport or whether they are restricted to a certain extent by their disorder? An important factor is freedom from seizures. If seizures have been controlled for over 2 years the risk of relapse is the same as the risk of a first seizure. The risk of patients drowning or falling, or their epilepsy worsening because they are engaged in sport is thought to be low. Clinical data suggest that the incidence of seizures during sports and exercise is reduced. In the cooling down period, however, seizures tend to occur more frequently. Physicians should encourage epileptic patients to participate in sporting activities to enhance their physical fitness, self-esteem, and social integration. Before giving advice about the most suitable type of sport, the physician should known the patient's medical history, have a good insight into the different types of sport and be able to judge the role and function of sport to the particular patient. With certain precautions virtually all sports are suitable for most epileptic patients and should therefore be encouraged. However, a small minority of hospitalised patients with severe epilepsy need the supervision of qualified trainers, coaches and volunteers. PMID- 2197702 TI - [Irritable colon and colonic disease due to laxatives]. AB - Diarrhea of colonic origin is fairly common in irritable colon and after long term abuse of laxatives. This form of diarrhea causes difficulties not only in diagnosis but also in treatment. Irritable colon is a functional disorder sometimes involving other segments of the bowel. The term "irritable bowel disease" is thus more appropriate. Extraintestinal symptoms are in addition quite common. Although the diagnosis can be established with great reliability using an index we consider some laboratory tests, recto-sigmoidoscopy and abdominal sonography essential to rule out organic lesions. Therapy comprises (small) psychotherapy, dietary measures and eventually transient medication. Symptoms usually persist but tolerance of the disorder should be improved. Laxative induced colonic dysfunction results usually from false assumptions about normal defecation. Loss of water and potassium deteriorates the symptomatology leading to a vicious circle. Alterations of neurons in the enteric nervous system of the colon can be the cause but eventually the consequence of chronic intake of laxatives. Hidden abuse of laxatives can cause great diagnostic difficulties. The therapy of choice is weaning which usually is only possible gradually. Cisapride can be a useful adjuvant. PMID- 2197703 TI - [The past and future of proctology]. AB - Since antiquity, surgical treatments of anorectal lesions were performed by barbers and surgeons; proctology became with time a surgical speciality well defined and recognized todays. History of proctology is illustrated by some important figures and events: St. Fiacre, Felix the surgeon who operated on King Louis XIV's fistula and the acutely thrombosed hemorrhoidal prolapse of Napoleon. PMID- 2197705 TI - [Diagnostic value of ultrasound in dentistry]. PMID- 2197704 TI - [Comparison of current proctological diagnostic studies]. AB - The proctological investigation is explained, and the importance of the digital examination is stressed. Modern techniques do not alter the traditional examination but give more information on specific questions. Endosonography, computed tomography and magnetic resonance imaging help a great deal in tumor investigation. Endosonography is especially helpful in the definition of tumor extension, judgement of the anastomosis and rectal wall and lymph node involvement. Computer tomography permits to detect infiltration in the bone, and magnetic resonance imaging a precise tumor extension because of the multiplanar image. The distinction between recurrent tumor and postoperative fibrosis is possible by the latter and endosonography. PMID- 2197706 TI - [The contribution of umbilical and cerebral Doppler velocimetry in the diagnosis and monitoring of intrauterine growth retardation]. AB - The authors studied the arterial circulation in the umbilicus and brain in 140 cases of intrauterine delayed growth using a pulsed Doppler system. Results were expressed in terms of a circulatory index. The Pourcelot resistance index is defined as S-D/S, where S represents the maximum systolic rate and D the maximum telediastolic rate and is used both for the umbilicus (Rp) and the brain (Rc). In order to evaluate the diagnostic and prognostic performance of the Doppler method, the values of the various indices were analyzed as a function of the foetal cardiac rhythm during labour, the method of delivery and the state of the infant at birth. The authors concluded that umbilical blood flow measurement was of moderate diagnostic values, while the unitary placental resistance index was of undeniable prognostic value (76 p. cent of foetal distress at birth, perinatal mortality of 30.30 p. cent). A pathological brain resistance index preceded the occurrence of abnormalities in foetal cardiac rhythm by 24 hours to 5 days in 64.28 p. cent of the cases and was always associated with foetal distress at birth. The authors considered it was important to take the respective short-term changes in values of the various circulatory indices into consideration rather than the isolated values themselves. The brain-placenta ratio (BPR = Rc/Rp) may perhaps constitute the best indication in the early screening of foetal hypoxia. PMID- 2197707 TI - [Invasive cervix cancer stage I and II in women less than 35 years old]. AB - The results of a retrospective study of 74 women under the age of 35, treated invasive cervical cancer, stage I and stage II, between 1973 and 1985, were compared with those obtained in 547 women over 35, treated during the same period of time for a similar cervical cancer. The treatment consisted of: association radium therapy-surgery for stages IB less than 25 mm and II A moderately extended and an association radiotherapy-radium therapy for stages IB greater than 25 mm and II A extended, II B and II C. A better distribution per stage is found in women under 35, identical regarding the histological type with 5-year survival identical in both groups at the same stage. Relapses or recurrences occur much earlier in younger women. In the literature, the age as a prognosis factor is very much controverted. On the contrary, other factors should be taken into consideration: clinical stage, node invasion, size and volume of the tumor, depth of infiltration of the cervix. PMID- 2197708 TI - [The contemporary history of breech delivery]. AB - After the last 50 years, the problems raised by breech presentation may be summarized as follows: during this period, foetal prognosis has been notably improved, the improvement is, nevertheless, considered to be insufficient in the present sociocultural context, the improvement has been brought about by various means and methods for which it is not easy to establish a ranking of values, too many differences remain concerning the significance of the presentation itself, as well as the results obtained with the various therapeutic approaches, these uncertainties prevent definition of the best management approach and, consequently, prevent fresh progress from being made, these uncertainties can only be removed by making an effort to integrate and summarize all that has been or will be published concerning the subject. PMID- 2197709 TI - [Epidemiology of rheumatic diseases in an ancient population. Study of the Necropole du Haut-Empire de Saint-Lambert (Frejus, Var)]. PMID- 2197710 TI - [Myasthenia associated with rheumatoid polyarthritis. An entity different from induced myasthenia?]. PMID- 2197711 TI - [The development of bone mass during a lifetime]. AB - The authors present a reminder of the methods used to evaluate the bone mass and density and, with population studies, specify the profile and significance of the physiological osteopenia in both sexes. Analysis of these studies shows that the age of onset of the bone loss and its percentage vary markedly between the various sites of the skeleton, according to the type of bone, cortical or trabecular. It seems that the "smooth" aspect of the physiological osteopenia curves obtained is women during population studies, essentially results from the disparity between the times of menopause. A general protocol of the physiological osteopenia, synthesizing all data collected with nine different methods of measurement of the mineral bone content, is presented for educational purposes. PMID- 2197712 TI - [Posterior articular pseudocyst]. PMID- 2197713 TI - The role of estrogens in schizophrenia gender differences. AB - The male/female differences that have been described in schizophrenia are important because they may ultimately shed light on factors that mediate the expression of schizophrenic illness. The hypothesis of this article is that estrogens, either directly or indirectly, modify symptom expression and account for many of the observed gender differences. The role of sex hormones is divided into organizational and activational effects. Organizational effects take place during a critical period in fetal life and put a permanent stamp on the developing brain. Activational effects are the direct influences of circulating hormones that appear when hormonal levels rise, and wane when hormonal levels drop. Because levels of sex hormones in adult women fluctuate during the menstrual cycle, cyclic effects of high and low female hormones may induce specific responses by the adult female brain. All these effects have implications for genetic, environmental, pharmacological, neurocognitive, clinical, and epidemiological research in schizophrenia. PMID- 2197714 TI - Influence of gender in schizophrenia as related to other psychopathological syndromes. AB - The evidence indicating that the forms of schizophrenia in men and women represent different morbid states is reviewed. Age of onset and gender are considered to be of fundamental importance in determining the different symptomatological and evolutionary features of the syndrome in the two sexes. Early-onset forms in males are associated with chronicity, absence of familial predisposition for psychosis, and the presence of structural cerebral pathology specifically involving the dominant hemisphere. Later onset forms in females are characterized by more florid symptoms, more affective features, more familial psychosis, and more favorable outcome with no or less pronounced structural cerebral involvement. It is argued that these differential characteristics derive from the differential hemispheric organization of the male and female brain- which also determines the male susceptibility to other psychopathological syndromes such as psychopathy and sexual deviations as well as the excess in women of schizoaffective states, affective disorders, and late-onset schizophrenia. PMID- 2197715 TI - Implications of olfactory agnosia for understanding sex differences in schizophrenia. AB - In our studies, 50 percent of the male patients with schizophrenia have an olfactory agnosia. This finding is of interest because the olfactory neuroanatomical network involves brain regions found to be abnormal in patients with schizophrenia, and this olfactory deficit appears to be sex dependent. This article reviews conceptual models for assessing olfactory function, describes the neuroanatomical structures involved, and reviews the findings of olfactory performance in patients with neurological dysfunction. The findings are then integrated with neuropathological studies of patients with schizophrenia. Finally, as there is increasing evidence for a sex difference in patients with schizophrenia, a model is suggested to account for these differences based on neuro-developmental and latent lesion hypotheses. PMID- 2197716 TI - Gender and schizophrenia outcome: a clinical trial of an inpatient family intervention. AB - Several studies document sex differences in premorbid and intermorbid role functioning, showing less functional deficit among females. The specific nature of sex differences in role functioning is still poorly understood. The purpose of the present study was to investigate sex differences in symptomatology and role functioning in a sample of 92 inpatients hospitalized for an episode of DSM-III diagnosed schizophrenic disorder. Patients were randomized at hospital admission to either of two treatment conditions: (1) multimodal hospital treatment with the addition of an inpatient family intervention (IFI) or (2) multimodal hospital treatment without IFI. Results indicated (1) sex differences in levels of substance abuse and antisocial behavior (worse for males both at admission and followup)--dimensions of psychopathology unrelated to the core features of schizophrenia; (2) superior family and occupational functioning in females at followup; and (3) superior clinical response of females to IFI. Data on family response to IFI suggest some ameliorative effects of IFI on critical family attitudes toward female patients as well as greater family compliance with IFI treatment among the families of females. Sex differences in intermorbid family and occupational functioning and response to a family-based psychosocial intervention are discussed in light of data on rejecting family attitudes toward the patient and sex differences in symptomatology. The possible influence of sex differentiated social role demands on response to IFI is also discussed. PMID- 2197717 TI - Blink rates in schizophrenia. AB - In schizophrenia, blink rates are frequently elevated and the peak of the electroencephalographic alpha rhythm is often absent or of a lower frequency. Emerging evidence suggests that both blinks and the alpha rhythm may be controlled by a linked neuroanatomical circuit that begins in rostral pons and involves several subcortical structures as well as the occipital cortex. Blink alpha abnormalities in schizophrenia further suggest that this blink-alpha neurocircuit may be a locus of the pathophysiological process of this disorder. PMID- 2197718 TI - [Combination insulin and sulfonylurea compounds in the therapy of type II diabetes mellitus]. PMID- 2197719 TI - [Supratentorial intracerebral hemorrhage]. AB - The data were reviewed of 76 patients with supratentorial intracerebral hemorrhage, including 38 lobar (LH) and 38 basal ganglion (BGH) hemorrhages. Our aim was to define the clinical and tomodensitometric profiles of the two lesions. Men seem to be at higher risk of BGH and women more frequently of LH. Among the risk factors and causes, only chronic hypertension proved to be clearly associated with BGH. Wide variability of clinical course was observed. However, LH was associated more frequently with headache, initial seizure and show installation over more than 12 hours. CT sections revealed association of intraventricular hemorrhage with BGH. No difference in short term prognosis was found between LH and BGH. PMID- 2197720 TI - What causes diabetes? PMID- 2197722 TI - Looking at medical history: vaccination. AB - Controversy with regard to medical procedures is not a new phenomenon. Two hundred years ago, vaccination against smallpox was both derided and acclaimed. The controversy engendered then can be "pictured" through the work of such graphic artists as James Gillray and Isaac Cruikshank. PMID- 2197721 TI - Ophthalmopathy in early thyrotoxicosis--relationship to thyroid receptor antibodies and effects of treatment. AB - A prospective study of 25 newly diagnosed thyrotoxic patients was undertaken to determine the incidence and severity of ophthalmopathy in the early stages of the disease. A quantitative analysis of the ocular muscle changes was made using B scan ultrasonography, and the effects of treatment for the thyroid disease on the course of the eye changes was assessed. Although the majority (75%) of patients showed only mild clinical signs of ophthalmopathy (Werner Class 3 or less), 92% had ultrasonographic evidence of ocular muscle enlargement. Clinical involvement of the extraocular muscles was seen in 12% of the cases. There was an inverse correlation between the serum level of thyroid stimulating hormone receptor antibody (TR Ab) and the size of the extraocular muscles. Recovery of the euthyroid state with treatment was accompanied by a decrease in orbital infiltration in some cases, both clinically (reduced amplitude of intraocular pressure rise on elevation of the globe) and by ultrasonography, but the improvement was not statistically significant. PMID- 2197723 TI - "Liver cancer ... or is it?". AB - There has been a gradual change in the pattern of presentation of pyogenic liver abscess with an increasing incidence in the elderly. At the same time an improvement in mortality with early diagnosis and treatment has been recognised. We describe two patients in whom the diagnosis of liver abscess was not suspected until autopsy in one and aspiration of pus during biopsy of a liver "tumour" in the other. PMID- 2197724 TI - John Knox Stuart, accoucheur extraordinaire. AB - John Knox Stuart of Glasgow epitomises the kind of 19th-century medical entrepreneur whose activities were intended to be curbed by the 1858 Medical Act. Druggist, obstetrician, builder, lecturer, poet and philanderer, his career was a chequered and eventful one. PMID- 2197725 TI - The thalassemia syndromes: molecular basis and prenatal diagnosis in 1990. AB - In this review I have outlined the molecular basis and prenatal diagnosis of alpha-thalassemia and then concentrated on the state of our knowledge of the molecular basis of beta-thalassemia and its prenatal diagnosis. I discussed the improved but more complicated genetic counselling now available as a result of our increased knowledge of the effects of various defects in the beta-globin gene. Our knowledge of the heterogeneous molecular basis of the thalassemia syndromes has become very impressive and it is hoped that effective therapy will soon follow. For the present, however, prevention of the birth of affected children is the most effective means of reducing the suffering associated with the thalassemia syndromes, and prevention of this type is succeeding in many parts of the world, including North America. PMID- 2197726 TI - Structural hemoglobin variants that produce the phenotype of thalassemia. PMID- 2197727 TI - Southeast Asian immigrants: the new thalassemias in Americans. PMID- 2197728 TI - Chronic granulomatous disease. PMID- 2197729 TI - Introduction and overview of interferon alfa in myeloproliferative and hemangiomatous diseases. AB - Both myeloproliferative and hemangiomatous diseases are characterized by abnormal cell proliferation. In myeloproliferative disorders, the abnormal growth involves hematopoietic progenitor cells of the marrow, whereas in hemangiomatous diseases, the abnormal growth involves endothelial cells of capillary blood vessels. Recombinant interferon alfa has shown promise in inducing remission in a number of myeloproliferative diseases, and, more recently, it has also been shown to be effective in treating several hemangiomatous disorders. In neither case is the mechanism of action of interferon alfa completely understood. PMID- 2197730 TI - Treatment of hemangiomatosis with recombinant interferon alfa. AB - Hemangiomas and lymphangiomas are two main types of angiomatous disease that occur most commonly in infancy and childhood. Most hemangiomas resolve spontaneously, but some endanger vital structures such as the lung, as in pulmonary hemangiomatosis, a rare and universally fatal disease. Occasionally, hemangiomatous lesions are associated with thrombocytopenia, consumptive coagulopathy (Kasabach-Merritt syndrome), and microangiopathic hemolytic anemia. In the past, treatment of hemangiomatosis has included corticosteroids, cytotoxic drugs, laser therapy, embolization or other surgical approaches, radiation therapy, cryotherapy, and supportive measures such as the administration of platelets or clotting factors. Recently, it has been found that recombinant interferon alfa is effective in treating pulmonary hemangiomatosis, as well as other variants of hemangiomatous disease such as hemangioendotheliomas. Possible mechanisms of action for interferon include inhibiting proliferation of endothelial cells, smooth muscle cells, or fibroblasts that have been stimulated by endothelial cell or fibroblast growth factors; enhancing the production of endothelial prostacyclin; or decreasing the production of collagen. It is also possible that interferon alfa antagonizes angiogenesis indirectly through its immunostimulatory actions. With the exception of significant hemodynamic changes in some patients during the first 48 to 72 hours of therapy with interferon, side effects are relatively mild. PMID- 2197731 TI - Update on therapeutic options for chronic myelogenous leukemia. AB - Chronic myelogenous leukemia (CML) is a myeloproliferative disorder triggered by a chromosomally induced mutation in a pluripotent stem cell. Its progressive clinical course consists of a chronic or benign phase, which terminates in blast crisis. Historically, treatment has been limited: conventional chemotherapy yields a median survival of approximately 36 to 42 months, and bone marrow transplantation, while achieving success in more than half of patients treated, is limited to younger patients with HLA-matched siblings. Treatment with interferon alfa in CML was initiated in 1981. The first studies were performed using partially pure interferon alfa; these studies were followed by treatment regimens employing interferon alfa-2a. PMID- 2197732 TI - [A decade of development of world culture and problems of health care]. PMID- 2197733 TI - [The history of eradication of pellagra in the USSR]. PMID- 2197734 TI - [Students of the Military Medical Academy during the reactionary period of 1907 1910]. PMID- 2197735 TI - [Historical and medical events and scientific medical discoveries]. PMID- 2197736 TI - [Problem of staging of the WHO activities]. PMID- 2197737 TI - [Experience with the work at a history of medicine museum]. PMID- 2197738 TI - [Efforts of the department of social hygiene and public health administration to preserve the memory of public health and medicine workers in Ufa]. AB - The authors believe that chairs of social hygiene and public health organization should carry out the work to perpetuate the memory of health workers, important events in the field of public health and medicine of different regions, districts, republics. Examples are found in the work conducted by the Chair of Social Hygiene and Organization of Public Health of the Bashkir Medical Institute. PMID- 2197739 TI - [Heroic deeds of medical personnel during the battle for Dnepr]. PMID- 2197740 TI - [History of public health in Kiev during the Second World War]. PMID- 2197741 TI - [A. T. Bolotov and Russian medicine in the 18th century]. PMID- 2197742 TI - [A. I. Meshchaninov: physician, scientist, patriot]. PMID- 2197743 TI - [Cooperative studies on the treatment of breast neoplasms, stage I, IIA, IIB and IIIB]. PMID- 2197744 TI - [Echography: a method of dynamic monitoring of the treatment of ovarian cancer]. PMID- 2197745 TI - [Splenectomy in diseases of the blood system]. PMID- 2197746 TI - [Epidemiology and surgical treatment of acute hemorrhoids]. PMID- 2197747 TI - Surgery in postmenopausal women--the value of transvaginal sonography. AB - Transvaginal sonography is a recent addition to the diagnostic techniques available for the evaluation of the female pelvis. Transvaginal sonography is performed with a high-frequency transducer placed in the vagina where it is in close anatomic proximity to the pelvic structures. The procedure overcomes difficulties in imaging obese patients, those with a large amount of bowel gas, and those with inadequate bladder filling. Our experience in over 200 cases of postmenopausal women is the subject of this review. This technique has been employed to detect ovarian and adnexal abnormalities, endometrial changes (hyperplasia and endometrial carcinoma), myometrial invasion, fibroids, adnexal torsion and free fluid in the rectouterine fossa. The results suggest that transvaginal sonography has considerable advantages in the evaluation of pelvic structures in postmenopausal women prior to planned surgical exploration. PMID- 2197748 TI - Rat liver model for testing intraoperative echo contrast sonography. AB - The present animal experimental study showed that intraoperative hepatic ultrasonography using an echo contrast medium can visualize small hepatomas (with a diameter of between 3 and 15 mm) induced in the rat liver, although they were not recognizable with plain ultrasonography. A homogeneous increase in the echogenicity of the liver tissue was achieved by using an echo contrast medium (Echovist) based on galactose microparticles. Self-made bubble preparations such as those used in echocardiography were far less effective. When the dosage was optimal (0.01-0.003 ml/g liver weight with concentrations of 200 and 300 mg/ml Echovist), homogeneous contrast enhancement of the liver was achieved for at least 10 min after a single bolus injection via all routes of contrast administration (hepatic artery, portal vein, bile duct). As a result, hepatomas appeared as hypodense formations (portal vein and bile duct) or as hyperdense zones (hepatic artery). PMID- 2197749 TI - Primary malignant melanoma of the esophagus. AB - This report describes a case of primary malignant melanoma of the esophagus in a 66-year-old man treated by esophagogastrectomy. Radiographic, endoscopic, echoendoscopic and histological features are given and a short review of the literature is presented. PMID- 2197750 TI - Esophageal varices evaluated by endoscopic ultrasonography: observation of collateral circulation during non-shunting operations. AB - To clarify the inflow and outflow vessels of esophagogastric varices, we investigated the collateral circulation using endoscopic ultrasonography (EUS; Olympus GF-UM2, 7.5 MHz, radial type) during non-shunting operations in 16 cases of portal hypertension. The main inflow vessels were the left gastric veins and the short gastric veins. The paraesophageal vessels coalescent with esophageal varices were distributed up to 7 cm from the esophagogastric junction. It was possible to devascularize these inflow vessels from the transabdominal approach, and it was also easy to evaluate the complete devascularization by the intraoperative EUS. The main outflow vein seemed to be the azygos arch from the investigation of cross-sectional areas of the azygos system. EUS is very useful in evaluating portal hypertension and in determining the indications and the efficacy of the treatment. PMID- 2197751 TI - [Loss of osseointegrated implants: analysis of causes of failure]. PMID- 2197752 TI - [Historical development of the cholesterol-atherosclerosis concept]. AB - The development of the cholesterol hypothesis to the cholesterol theory, as related to atherogenesis, is followed in chronological sequence. The major milestones in terms of chemical pathology of the lesions, clinical observations on serum cholesterol levels in patients with coronary heart disease, lipoprotein research, epidemiological investigations and prevention of diseases due to atherosclerosis are described within three time periods: from the 19th till the beginning of the 20th century, the years between the two World Wars and the last 40 years. A total picture emerges which assigns to cholesterol and its lipoprotein carriers a key role in the origins and progression of atherosclerosis. These causal relationships have opened the way to the prevention of the disease, supported by intervention studies aimed at reduction of serum cholesterol levels. PMID- 2197753 TI - Strategy for diagnosis and treatment of hyperlipidemia. AB - As hypercholesterolemia is an essential risk factor of atherosclerosis, a strategy for diagnosis and treatment of hyperlipidemia is indispensable. Differences in mortality from coronary heart disease in different cultures seem to be due to environmental, not to genetic factors. Trials in Finland and the United States have shown that cholesterol levels and smoking can be reduced by information and education with an ensuing drop in cardiovascular mortality. This experience warrants national programmes for cholesterol-lowering in high risk countries. Programmes should be directed to doctors and health officials as well as legislators and the public. Within any given population individual differences of lipid levels are due to both nutritional habits and genetic variations concerning e.g. LDL-receptors and lipase activity. At present the only means of identifying subjects at risk is to measure their lipid levels and to scrutinize their family history. Measurements should be repeated to exclude biologic and laboratory variability. Drugs currently available include HMG CoA reductase inhibitors, bile acid binding resins, clofibrate derivatives and nicotinic acid. Formerly defined age groups with regard to therapeutic measures have meanwhile been abandoned. PMID- 2197754 TI - [A favorable hyperlipoproteinemia: high-density lipoproteins and atherosclerosis]. AB - A full, clinical appreciation of blood cholesterol levels necessitates recognition of the divergent influences of cholesterol associated with low density lipoprotein (atherogenic) and high density lipoproteins (HDL, anti atherogenic) on the atherosclerotic process. Convincing evidence now exists to show that raising HDL-cholesterol levels reduces the incidence of cardiovascular disease, thus providing a firm rationale for therapeutic measures designed to favourably modify its plasma concentrations. In this respect, association of lower HDL-cholesterol levels with an unhealthy life style (smoking, lack of exercise, obesity) is of particular relevance. Whilst still a subject of discussion, available data strongly support the inclusion of HDL-cholesterol measurements when establishing plasma lipid profiles. PMID- 2197755 TI - [Drug treatment of hyperlipidemia]. AB - The working panel of the Swiss Foundation for Cardiology has elaborated in 1989 new directives for the treatment of hyperlipaemias. Cholesterol values over 6.5 mmol/l with a cholesterol/HDL ratio over 5 and, in case of coronary heart disease, cholesterol values over 5.2 mmol/l should first be treated by diet. If after 3-6 months, in spite of dietary treatment, cholesterol values remain superior to 6.5 mmol/l or the cholesterol/HDL ratio superior to 6.5, drug treatment must be considered in case of coronary heart disease or arteriosclerosis, considerably abnormal lipid values (cholesterol greater than 7.8 mmol/l; in case of coronary heart disease: cholesterol greater than 6.5 mmol/l), other risk factors, positive family history for coronary heart disease and younger men. Most of the medicaments available today reduce total cholesterol by 10-30%. Combined therapies can be indicated, if in the presence of high risks the different possibilities of monotherapy have not led to the desired success. PMID- 2197756 TI - [Gastroenterologic laser surgery]. PMID- 2197757 TI - [Health status during the occupation years--morbidity]. AB - We refer to several studies on different aspects of the health status of the Norwegian population during World War II. The failure of the food supply led to various symptoms caused by deficient diet which reduced the resistance to infection. Hygienic problems increased, access to medical services deteriorated, and resources in terms of hospital beds, economic appropriations and number of health personnel were reduced, in particular during the final years. A network of factors contributed to deterioration in the health of the population. After the occupation the health status improved very quickly, evidently due to rapid access to the medical resources organized by the Norwegian public authorities in exile. PMID- 2197758 TI - [Health status during the occupation years--mortality]. AB - The crude total death rate of the Norwegian population gradually decreased from the early 1930s until 1940. During the German occupation the total death rate increased moderately, but markedly, particularly among males and age groups below 45 years. Children too had a high death rate, due to an extremely high occurrence of infectious diseases. Infant mortality declined, however, particularly in the cities, probably due to increased resources in mother and child health care. In all age groups mortality was generally dominated by injuries and violent causes of death, in addition to infectious diseases. The concept that cardiovascular diseases became less frequent due to favourable changes in diet and life style is doubtful. The statistical decline in mortality from these diseases started before the quality or quantity of the diet was reduced to any extent, and the rise began before diet and nourishment improved. Further, the routines for reporting death, and the nomenclature, were changed already in 1941, making comparisons between the prewar and the war period difficult. The figures may thus be due to artefacts. In addition, the high frequency of violent and unknown causes of death may mask the possible effects of chronic and lethal diseases. PMID- 2197759 TI - [Health conditions in Sor-Varanger during the war years 1940-44]. AB - The author, who was District Medical Officer in the municipality of Sor-Varanger during World War II, has described the health status of the 7,000 Norwegians during these years of German occupation. Sor-Varanger is situated in the northern part of Norway and was close to the German-Russian combat zone. The municipality was heavily attacked by air raids. The population suffered from undernourishment and there were outbreaks of several types of epidemics. PMID- 2197760 TI - [Health status during the occupation years--from a family practice at Laksevag]. AB - Patient records for the period 1940-46 from a "double" family practice at Laksevag near Bergen were analysed in order to study the occurrence of different diagnoses. The main diagnoses from 8,025 consultations were processed. The panorama of diseases seems to be dominated by infectious diseases and injuries. These complaints were more frequent than in similar records of practice 30 years later. By comparison, cardiovascular, psychiatric and musculosceletal diagnoses were much more rare. On average, the patients were younger than those described, in the records from 30 years later. PMID- 2197761 TI - [From the history of brain research]. AB - This paper describes the understanding of the brain and central nerve system from antiquity up to our own century. It also describes the first attempts at brain research in the Nordic countries, and in Norway in particular. PMID- 2197762 TI - [The black death in Norway]. AB - The old Icelandic annals tell that the Black Death came to Bergen, Norway, in 1349 with a ship from England. This was probably at the beginning of September. From Bergen the plague spread rapidly northwards and southwards along the coast and over land to Eastern Norway. The Black Death remained in Norway for approximately six months. The epidemic must have been started by infected black rats and rat fleas in the grain cargo of the ship. The account in the annals, and experiences from other countries, indicate that pneumonic plague was dominant in Bergen at the start of the epidemic. After that the Black Death must have spread partly as pneumonic plague but mainly probably as bubonic plague, transmitted via human fleas from person to person. The rats cannot have played a part except in the initial phase. The annals say that 2/3 of Norway's population died. This is probably a big exaggeration. The mortality in Norway can hardly have been more than 40-50%. Even this is high compared with an estimated mortality of approximately 33% in England and on the continent. PMID- 2197763 TI - [Anatomy of the pelvic joints]. PMID- 2197764 TI - [Toxicology in development and its relationship to pharmacology]. PMID- 2197765 TI - Arteriovenous fistulas after median sternotomy--report of 2 cases and review of the literature. AB - We report 2 cases of arteriovenous fistulas as a very rare complication following median sternotomy. In the first case a fistula was observed between the right internal mammary artery and vein caused by a sternal wire. The second patient developed a fistula between the innominate artery and left innominate vein after suture repair of a slight hemorrhage from the innominate vein. The latter localization has not been previously described. In both cases the fistulas were discovered by a continuous murmur appearing 12 and 11 days postoperatively. The therapy consisted of resternotomy and resection of the fistulas. The literature is reviewed and etiology, diagnosis and therapy are discussed. PMID- 2197766 TI - [The possibility of the incorporation of macromolecules, including exogenous DNA, into the germ cells of male mice. The liposome method and Ca-P coprecipitation method]. AB - Liposomes loaded with FITC-labeled albumin in the presence of PEG-1,500 are actively sorbed on the membranes of mature spermatozoa and remain attached even after thorough washing. Immature sperm cells are able to incorporate alien DNA carried by liposomes. In contrast, the mature spermatozoa could not incorporate plasmid DNA loaded with positively charged liposomes. Chlortetracycline in Ca-P coprecipitate crystals is tightly fixed in the postacrosomal region of mature sperms. Intensity of staining of chlortetracycline is stimulated by DNA load in Ca-P coprecipitate as well as by DMSO or EDTA. The method of Ca-P coprecipitation could not provide for plasmid DNA incorporation into taure sperms. Foreign DNA incorporation in postacrosomal regions of sperm heads seems quite possible in experiments with dimethylsulphoxide (DMSO). PMID- 2197768 TI - Transurethral prostatectomy. AB - Transurethral prostatectomy is one of the most common operations today. In the United States, more than 90 per cent of patients with bladder outlet obstruction from BPH have their surgery done transurethrally. The operation is associated with a very low mortality rate, and the immediate postoperative results are excellent. The long-term results also appear to be satisfactory according to chart review data. However, insurance claims data suggest higher later mortality and reoperation rates than have been reported previously. Further studies, such as a randomized trial, will be necessary to evaluate the long-term outcome of transurethral prostatectomy further. PMID- 2197767 TI - Detection of clinically occult prostate cancer. AB - A large number of cases of prostatic carcinoma are discovered unexpectedly by simple prostatectomy performed for presumed benign disease. The ability to discover these cancers preoperatively is an appealing concept, in other words, to screen: the use of a test to detect a disease in an asymptomatic individual. The ideal screening test would be noninvasive, inexpensive, reliable, and reproducible. It would also have a high sensitivity and specificity, neither allowing a disease process to be missed by a falsely negative result nor leading to unnecessary and more invasive studies by a falsely positive one. It has been suggested that an acceptable screening test have a sensitivity of at least 95 per cent and a specificity of 100 per cent. An equally important criterion for a successful screening program for cancer has to do with the biologic potential of the discovered malignancy. The adage is that more men die with prostate cancer than of prostate cancer. However, the biologic potential of prostate cancer has not been fully elucidated, and it is not entirely clear who will benefit from treatment and who should be left alone. At the present time, noninvasive imaging modalities and biochemical markers are not clinically useful in detecting occult prostatic carcinoma. Furthermore, no study has proved that routine screening reduces the mortality rate from prostate cancer. Many authors believe that screening men for prostate cancer should be regarded as investigational and that currently, only screening programs for breast and cervical cancer have been fully demonstrated to be effective. New studies are needed that include control groups who are not subjected to the early diagnostic modality, assessing both the disadvantages of the screening program and the potential benefits. PMID- 2197769 TI - American Urological Association survey of transurethral prostatectomy and the impact of changing medicare reimbursement. AB - The American Urological Association, in a survey of all American urologists, found that TURP accounts for 38 per cent of their major surgery and also found that activities associated with the operation account for nearly 25 per cent of their total patient workload. American urologists regard TURP as complex, and they believe proficiency requires more practical case experience during residency training than is required for any other urologic operation. American urologists assign TURP a significantly higher relative value than that proposed in the pending national Medicare Fee Schedule formulated by medical economists and the Physician Payment Review Commission. The legislated reductions in allowable Medicare fees for TURP and the possible shift in management of benign prostatic hyperplasia to nonsurgical methods create a financial vulnerability for American urologists who remain economically dependent on this dominant operation. Adjustments in practice patterns and manpower policy planning may well be required. PMID- 2197770 TI - Use of antimicrobials for patients undergoing prostatectomy. AB - Our suggestions for the use of antimicrobials in patients undergoing prostatectomy are summarized in Table 2. The use of antimicrobial prophylaxis perioperatively for patients without bacteriuria remains controversial. Some authors recommend and others do not recommend antimicrobial prophylaxis. We do not recommend perioperative prophylaxis for low-risk patients without previous urinary tract infections or an indwelling urethral catheter. We do recommend that patients with risk factors that increase the rate or consequence of urinary tract infection, those with previous urinary tract infections, or those with indwelling urethral catheters, even though the urine shows no growth, receive perioperative antimicrobial prophylaxis. Antimicrobial therapy is mandatory for patients with preoperative bacteriuria. The drug must be selected according to the susceptibility of the pathogen, and the duration of treatment must be guided by the severity of the infection. At the time of catheter removal, antimicrobial prophylaxis is probably beneficial, and antimicrobial therapy is essential if bacteriuria is present prior to catheter removal. All patients must have cultures after catheter removal and antimicrobial therapy if a urinary tract infection is identified. PMID- 2197771 TI - Impotence after prostatectomy. AB - Reportedly, 4 to 30 per cent of patients suffer impotence after prostatectomy. Some cases of neurovascular impotence can be attributed to the surgical technique. The author examines the incidence and mechanisms of such impotence and outlines the evaluation and treatment options. PMID- 2197772 TI - Transurethral resection versus transurethral incision of the prostate. A prospective randomized study. AB - In this ongoing study, patients with an estimated prostate size of no more than 20 gm are randomized to undergo either transurethral resection of the prostate (TURP) or transurethral incision (TUIP) at the 6 o'clock position. To date, 93 patients have been included, and 3 months postoperatively, 80 to 90 per cent of the patients in each group reported improvement. There was also a significant decrease in symptom scores and a significant increase in maximum urinary flow rate, with great variation within each group but without difference between the groups. In both groups, there appears to be some deterioration over time. Operating time, estimated blood loss, time to catheter removal postoperatively, and duration of postoperative hospital stay were all significantly in favor of TUIP. Loss of ejaculation was reported by 37 per cent of patients after TURP and by 13 per cent after TUIP (not statistically significant). There was no difference between the groups in the need for further surgery. Therefore, TUIP is recommended as an alternative to TURP in patients with small prostates. PMID- 2197774 TI - [In search of reserves of renewal (Rinat Fattakhovich Tagirov)]. PMID- 2197773 TI - [Determination of antibodies to Streptococcus agalactiae in the milk of dairy cows using the ELISA test]. AB - A sensitive 4-layers ELISA test for determination of antibodies against the pathogens of Streptococcus agalactiae in cows' milk was used for diagnosis of mastitis, with the aim to broaden these methods. Antigen was linked on the solid phase in the form of the whole bacteria, and milk was tested, diluted in the ratio of 1:10. Antigen bound-specific antibodies were labelled with pig antibodies against bovine immunoglobulins and in the next layer with rabbit antibody conjugated with peroxidases against pig immunoglobulins. After test visualisation and reading on the photometre, the results were given in the positivity per cent as a 100-multiple of the proportion of absorbance of the unknown sample and the positive control after subtraction of the negative control. Milk was examined in 36 dairy cows from three various breeding herds by that method. The samples were parallelly examined bacteriologically and cytologically. In the milk of dairy cows with positive S. agalactiae finding, the main level of antibodies expressed a positivity per cent, was 15.0%, while in bacteriologically negative animals it was only 6.2%. The dairy cows were divided into 8 groups, characterizing various stages of mastitis, according to the results of the individual treatments. PMID- 2197775 TI - [The organization of medical support for the Soviet troops in the Vistula-Oder operation]. PMID- 2197776 TI - [Supplying medical services to the Balaton defensive operation]. PMID- 2197777 TI - [A device for the acquisition of stable relaxation habits]. PMID- 2197778 TI - [N. P. Kravkov--the first laureate of the V. I. Lenin Prize]. PMID- 2197779 TI - [50 years guarding the health of soldiers]. PMID- 2197780 TI - [The experience of military field surgery in the Soviet-Finnish War]. PMID- 2197781 TI - [V. I. Lenin and Soviet public health]. PMID- 2197782 TI - Pulmonary artery pressure measurements. PMID- 2197783 TI - Analysis of nursing administration research, 1976-1986. PMID- 2197784 TI - [The 1st University Women's Hospital from Friedrich Schauta until today]. PMID- 2197785 TI - [From the establishment of the 1st Women's Hospital in Vienna (1789) until the appointment of Friedrich Schauta (1891)]. PMID- 2197786 TI - [Obstetrics in Vienna until the establishment of the University Women's Hospital]. PMID- 2197787 TI - [The development of the Radium Department of the 1st University Women's Hospital into the Radiation Department of the 1st and 2d University Women's Hospital, Vienna (a 39-year retrospective)]. PMID- 2197788 TI - [The Hormone Laboratory of the 1st University Women's Hospital, Vienna, from 1969 to 1989]. PMID- 2197789 TI - World malaria situation, 1988. Division of Control of Tropical Diseases. AB - Indigenous malaria continues to occur in some 100 countries or areas. Excluding the WHO African Region where reporting is fragmentary and irregular, the trends in individual countries of the different regions vary, but an upward trend in the number of malaria cases reported in the Americas and some Asian countries, is clearly visible. Some 83% of the total number of cases reported annually to WHO (excluding the African Region) are concentrated in Afghanistan, Brazil, China, India, Mexico, the Philippines, Sri Lanka, Thailand and Viet Nam. Within these countries malaria shows a marked focalization. Of a total world population of about 5,061 million people (1988), 2,988 million (59%) live in areas free of malaria (it never existed, disappeared or was eliminated by antimalaria campaigns and the malaria-free situation has been maintained). 1,599 million people (32%) live in areas where endemic malaria was considerably reduced or even eliminated but transmission was reinstated and the situation is unstable or deteriorating. These areas include zones with the most severe malaria problems which developed following major ecological or social changes; these zones comprise only about 1% of the world population. Areas where endemic malaria remains basically unchanged and no national anti-malaria programme was ever implemented, are inhabited by 474 million people (9%), mainly in tropical Africa. In Africa south of the Sahara, 2 7 million cases are reported each year, but by extrapolating from fever and parasite surveys one can estimate that about 90 million clinical malaria cases may occur in tropical Africa every year, and that prevalence of infection may be in the order of 250 million parasite carriers. Endemicity reaches the highest levels in the world, with very large areas classified as holoendemic. Where endemicity decreases, marked seasonality and the quasi-cyclic occurrence of heavy rains lead occasionally to epidemics or serious exacerbations of endemicity. The lack or shortage of trained personnel for the planning, organization, monitoring and evaluation of programmes remains one of the major constraints in many countries. The policy advocated is the development of malaria control within the framework of primary health care at the district level. The aim is the prevention and reduction of malaria mortality by providing prompt diagnosis or recognition and adequate treatment of malaria cases through the basic health services and primary health care. This implies also the creation of efficient referral systems for the management of severe and complicated cases, and for treatment failures.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2197790 TI - Genetic and nutritional factors in the etiology and pathogenesis of diabetes mellitus. PMID- 2197791 TI - Hypertension: genetics and nutrition. PMID- 2197792 TI - Cancer: genetic and nutritional aspects. PMID- 2197793 TI - Genetic individuality and nutrition. PMID- 2197794 TI - Genetic epidemiology of ethanol metabolic enzymes: a role for selection. AB - Human ethanol consumption has a profound impact on nutritional status, causing major alterations in intermediary metabolism and critical deficiencies of vitamins and trace elements. The major enzyme systems responsible for the principal steps in ethanol metabolism have been characterized and the genes cloned, and significant functional polymorphisms have been identified. An inactive allele of the mitochondrial ALDH is associated with flushing and reduced alcohol intake. This allele may also confer greater sensitivity to some of ethanol's toxic effects. In populations not possessing this variant, twin and adoptive studies have revealed that heritability for alcoholism is greater than 50%. The occurrence of three functional polymorphisms in the ethanol metabolic pathway, including two mutations which are conserved across populations, suggests a role for selection in their maintenance. The two general categories of selective forces to maintain these polymorphisms are food toxins and infectious diseases. Of the infectious agents, amoebi and other anaerobic and microaerophilic organisms of the gut are the most logical candidates. PMID- 2197795 TI - Genetic influences on nutritional thresholds. PMID- 2197796 TI - Nutrition, genetics, and aging. PMID- 2197797 TI - The role of nutrients in gene expression. PMID- 2197798 TI - Genetics of taste and smell. PMID- 2197799 TI - The role of genetics in idiosyncratic reactions or adverse reactions to foods. PMID- 2197800 TI - Genetic differences in risk of disease within and between populations. PMID- 2197801 TI - Linkage methods for identifying genetic risk factors. PMID- 2197802 TI - Genetics and nutrition: or what your genes can tell you about nutrition. PMID- 2197803 TI - Risk estimates and genetic screening as public policy. PMID- 2197804 TI - Genetic variation and nutrition: obstacles and opportunities in science education. PMID- 2197805 TI - Cultural transmission and nutrition. PMID- 2197806 TI - Molecular genetics and nutrition. PMID- 2197807 TI - Changing heritability of nutritional disease: another explanation for clustering. PMID- 2197808 TI - Individuality, hyperlipidemia, and premature coronary artery disease. PMID- 2197809 TI - Environmental and genetic risk factors for coronary heart disease. Current state of the WHO genetic case-control and family study. PMID- 2197810 TI - Potassium supplements vs. potassium-sparing diuretics. PMID- 2197811 TI - Inhaled aminoglycosides in cystic fibrosis. PMID- 2197812 TI - Accuracy of home pregnancy tests. PMID- 2197813 TI - Coagulase-negative staphylococci: incidence, pathogenicity, and treatment in the 1990s. AB - Coagulase-negative staphylococci (CNS), which historically have been viewed as contaminants when recovered in culture media, are now recognized as opportunistic pathogens of increasing importance in hospital-acquired infections. They are frequently found colonizing prosthetic devices and intravenous lines. CNS are capable of producing a variety of infections including deep-seated infections such as endocarditis and meningitis. Staphylococcus epidermidis is the most commonly isolated CNS and it appears to be the most resistant to antibiotics, making antimicrobial therapy challenging. Treatment of the infection will very often require removal of a prosthetic device, if present. An adequate infection control program is imperative in prophylaxis against this infection. PMID- 2197814 TI - Pharmacologic interventions for the treatment of opioid dependence and withdrawal. AB - This article discusses current pharmacologic methods in the treatment of heroin dependence and withdrawal. Methadone hydrochloride, the most commonly used opiate agonist, is used for both withdrawal and maintenance therapy. However, it produces dependence and withdrawal results upon abrupt discontinuation. Other opiate agonists including L-alpha acetyl methadyl (LAAM) and propoxyphene napsylate have been used for both withdrawal and maintenance therapy. LAAM is currently available only as an investigational agent and propoxyphene is easily accessible but has been associated with hallucinations and dysphoria at high doses. Alpha 2-adrenergic agonists decrease opiate withdrawal symptoms by decreasing the central adrenergic hyperarousal that is associated with withdrawal. Clonidine effectively attenuates but does not totally eliminate withdrawal symptoms. Other alpha 2-adrenergic agonists (e.g., lofexidine hydrochloride, guanfacine hydrochloride, and guanabenz) have undergone only preliminary investigations. Although alpha 2 agonists effectively decrease most withdrawal symptoms they often cause hypotension. Buprenorphine hydrochloride is a partial opiate agonist that shows some promise in the treatment of the heroin dependent population. It attenuates opiate craving and causes only minimal withdrawal upon abrupt discontinuation. Because it is well accepted by the heroin dependent population, however, it may ultimately become an abused substance. Naltrexone is a potent, orally acting opiate antagonist that blocks all opiate agonist effects and causes no euphoria. Unfortunately, it has not been well accepted by the heroin-dependent population. Scant research has been conducted concerning the use of adjunctive medications during opioid withdrawal. PMID- 2197815 TI - What is the clinical role of aerosolized ribavirin? AB - Aerosolized ribavirin is the first approved agent for the treatment of respiratory syncytial virus (RSV) infection. However, the clinical use of ribavirin is controversial. Although ribavirin-treated patients appear to be subjectively improved, the benefit in terms of decreased morbidity and mortality is not well established. Furthermore, the drug has been found to be teratogenic, carcinogenic, and mutagenic, depending upon the scientific model. Because of its unique mode of administration, environmental exposure of healthcare personnel and other patients may occur. Although administration in mechanically ventilated patients decreases the amount of ribavirin liberated into the atmosphere, the drug crystallizes in the endotracheal tube, occasionally resulting in reduced ventilation. The lack of data documenting efficacy and the above environmental concerns result in difficult decisions for hospitals. Further studies are necessary to clarify the value and safety of ribavirin in the treatment of RSV infection. PMID- 2197816 TI - Clomipramine: a tricyclic antidepressant effective in obsessive compulsive disorder. AB - Clomipramine hydrochloride, a chlorinated analog of imipramine, is a widely used antidepressant recently approved for use in the U.S. for the treatment of obsessive-compulsive disorder (OCD), a potentially incapacitating affliction. Its primary pharmacologic action is blockade of the reuptake of the neurotransmitter serotonin. Its metabolite, desmethylclomipramine, is a potent norepinephrine reuptake inhibitor. Significant first-pass metabolism reduces oral bioavailability to less than 62 percent. The drug is widely distributed throughout the body (volume of distribution 9-25 L/kg) and is 90-98 percent protein-bound. Clomipramine follows first-order elimination pharmacokinetics, with a plasma half-life of 20-24 hours. Recent double-blind controlled clinical trials have demonstrated the drug's effectiveness in the treatment of OCD. Response is most often associated with doses greater than 75 mg/d, with 250 mg the maximum recommended daily dose. Relapse upon withdrawal is frequently reported. The adverse effect profile of clomipramine is similar to other tricyclic antidepressants, with anticholinergic, cardiovascular, sexual, and central nervous system effects the most prominent. PMID- 2197817 TI - Moricizine: a novel antiarrhythmic agent. AB - Moricizine is a phenothiazine derivative with Vaughan Williams class 1 antiarrhythmic properties. It undergoes extensive first-pass metabolism, has a bioavailability of 34-38 percent, and is 95 percent bound to plasma proteins. Moricizine is extensively metabolized and may have pharmacologically active metabolites. A recent clinical study has shown that moricizine is slightly less effective than encainide or flecainide in suppressing ventricular premature depolarizations. Compared with disopyramide and quinidine, moricizine was equally or more effective in suppressing ventricular premature depolarizations, couplets, and nonsustained ventricular tachycardia. Further studies are needed comparing moricizine with other class 1 agents in the treatment of life-threatening arrhythmias; available data suggest that moricizine is comparable with these agents in the treatment of ventricular tachycardias and fibrillation. Moricizine appears to have a low incidence of serious adverse effects compared with other antiarrhythmics. This combination of apparently similar efficacy with a decreased incidence of adverse effects makes moricizine a worthwhile addition to currently available antiarrhythmic agents. PMID- 2197818 TI - Zidovudine update: 1990. AB - Zidovudine (ZDV) is the only approved antiviral for the treatment of human immunodeficiency virus infection (HIV) in the U.S. Although newer antivirals have reached Phase II testing, ZDV is now the accepted therapy against which all other agents will be compared. Zidovudine 1500 mg/d was previously prescribed only to adult HIV-infected patients who had developed AIDS or AIDS-related complex (ARC). However, results obtained from recently completed studies indicate that a lower daily dose (500 mg) appears to be equivalent. In addition, ZDV therapy appears to be beneficial to asymptomatic HIV-infected patients with CD4+ counts less than 500/mm3. The toxicity profile of ZDV, previously obtained from patients receiving 1500 mg/d, consisted of either acute (e.g., fever, rash, headache) or chronic (e.g., anemia, neutropenia, myopathy) adverse effects. ZDV pharmacokinetics are variable within and between the different subpopulations of HIV-infected patients who have been studied. Bioavailability ranges from 50 to 70 percent, and values for half-life, total body clearance, and volume of distribution are 1-2 h, 20-40 mL/min/kg, and 1-2 L/kg, respectively. Drug interactions occur primarily between ZDV and other agents that undergo hepatic glucuronidation (e.g., probenecid, sulfamethoxazole) resulting in decreased ZDV clearance. ZDV is currently measured by HPLC, radioimmunoassay and FPIA; however, the role of therapeutic monitoring is currently under investigation. Studies of ZDV therapy in neonates, pediatric patients, patients with resistant isolates of HIV, and HIV-infected patients receiving combined treatment with other reverse transcriptase inhibitors or immunomodulators are ongoing. PMID- 2197819 TI - [The significance of free radicals in cardiology]. PMID- 2197820 TI - [Shift work and hypertension]. PMID- 2197821 TI - [Chronic lymphedema of the extremities]. PMID- 2197822 TI - [New aspects in therapeutic use of ursodeoxycholic acid]. PMID- 2197823 TI - [Diagnostic imaging in liver diseases--personal experiences]. PMID- 2197824 TI - [Planning clinical trials and observing ethical principles from the biometric viewpoint]. PMID- 2197825 TI - [Developmental status and trends in laser medicine technics]. PMID- 2197826 TI - [Application procedures and indication areas for using lasers in gynecology]. PMID- 2197827 TI - [Laser surgery experiences in ENT practice]. PMID- 2197828 TI - [Nocturnal continuous subcutaneous insulin infusion--a therapeutic possibility in labile type I diabetes under exceptional conditions]. AB - The whole-day continuous subcutaneous insulin infusion (CSII) with portable pumps in daily blood glucose autocontrol guarantees a more stabile and favourable glycaemia than multiple injections in labile type I diabetics. The success is mainly to be traced back to the continuous replacement of the basal secretion, particularly to the nocturnal fasting phase. In this study the effect on the glycaemia is investigated with exclusively nocturnal administration of the CSII under maintenance of multiple insulin injections during this day. In a group of 18 type I diabetics the nocturnal CSII in comparison to intermediate insulin administrations in the evening led to a significant improvement of glycaemia (p less than 0.01), in particular to the decrease of the fasting blood sugars (p less than 0.05). In two casuistic observations in comparison to all the other conventional methods for the compensation of the nocturnal glycaemia (depot insulin, nocturnal injection of normal insulin) the nocturnal CSII proved to be superior. Therefore, the nocturnal CSII is an--though more rarely to be used- alternative, which may be taken into consideration, of a whole-day CSII is temporarily unwished for. PMID- 2197829 TI - [Halle physicians as historians and specialty chronologists. VI. From the early memoir literature]. AB - The regional contribution about physicians as witnesses of time directed to Halle and the university of the city on river Saale in the 20th century dazzles into dark chapters of the history of German medicine and higher education. Thereby the recent local literature of memoirs contains remarkable statements concerning the events of the years between 1933 and 1945. The written reminiscences of several university teachers really do justice to the postulates to be directed to this genre. PMID- 2197831 TI - The Fifteenth International Conference on Yeast Genetics and Molecular Biology. The Hague, The Netherlands. July 21-26, 1990. Book of abstracts. PMID- 2197830 TI - [Primary malignant teratoma of the spleen]. AB - It is reported on the unusually rare case of a primary malignant teratoma of the spleen. Course of diagnosis and therapy are discussed. PMID- 2197832 TI - The International Community of Yeast Genetics and Molecular Biology. PMID- 2197833 TI - Detection of significant vesico-ureteric reflux by ultrasound in infants and children. AB - We evaluated real-time ultrasonography in the diagnosis of vesico-ureteric reflux by comparing its findings to those of dynamic micturition cystourethrography. The study material comprised 124 consecutive infants and children referred to uroradiological workup, usually because of a relapsing febrile urinary tract infection. Both examinations were done during the same session. Consistent findings were obtained on 232 ureters, of which 37 displayed II. and 19 III. + reflux. II. reflux was found in 12 ureters by cystography only; thus one-fourth of low-grade refluxes escaped the diagnosis by ultrasound. The false negative findings of ultrasound examination included also two ureters showing III. reflux in cystography. As calculated for therapy-requiring (grade III or higher) reflux, the sensitivity of ultrasound was 90 per cent and its specificity 100 per cent. We conclude that ultrasound can be used as a primary diagnostic technique for girls, and in the follow-up of both boys and girls. PMID- 2197834 TI - Congenital urethroperineal fistula: a case report and literature review. AB - Congenital "H type" urethroanal and urethroperineal fistulas are extremely rate anomalies. The treatment of these pathologies is very complex and there is no well established surgical approach. An urethroperineal fistula is presented and the treatment is discussed. Additionally the literature in English on the subject is reviewed. PMID- 2197835 TI - [Hamartoma of the breast]. AB - Two cases of hamartoma of the breast are presented. The clinical findings of this benign, rare lesion are not specific. It is characterized radiologically by its typical features of a clear or heterogeneous well defined picture with radiolucent zones on mammography. Echography provides no specific picture. Histologically, the tumor is composed of normal or dysplastic mammary tissue. Surgical treatment is mandatory, an enucleation can usually be performed. PMID- 2197837 TI - [Acute acalculous cholecystitis: apropos of 6 cases]. AB - Authors relate their experience of six cases of acute acalculous cholecystitis (4 postoperative, 2 posttraumatic and postoperative). Five cases were correctly diagnosed preoperatively and another case was operated on the basis of a high index of suspicion. Acute acalculous cholecystitis is often misdiagnosed and its frequency is probably higher than suspected. Associated diseases, the natural history of the disease as well as delayed diagnosis explain its poor prognosis. The diagnosis of acute acalculous cholecystitis should be routinely ruled out in high risk patients (polyoperated, polytraumatised) in order to improve the mortality rate. Ultrasonography and biliary scintigraphy are useful for the diagnosis in high risk patients. Emergency cholecystectomy is still the best long term treatment. PMID- 2197836 TI - Elective cholecystectomy without drainage and without prophylactic antibiotics. A prospective randomized trial with clinical and bacteriological aspects. AB - A consecutive series of 50 patients undergoing elective cholecystectomy without prophylactic antibiotics entered a prospective randomized trial to compare the post-operative clinical course whether the subhepatic space was drained or not. 26 patients (mean age 58 yrs) were drained and 24 patients (mean age 59 yrs) were not. The incidence of positive gallbladder bile cultures were respectively 8 and 19% (N.S.) in the drained and undrained groups. The incidence of post-operative mortality, thrombo-phlebitis and intra-abdominal sepsis was zero in both groups. In the drained or undrained series, the incidence of wound infection was respectively 4% and 0% (N.S.), that of urinary infection was 8% and 13% (N.S.) and that of pulmonary atelectasis was 15 and 17% (N.S.). A further consecutive series of 100 undrained elective cholecystectomies (18% positive bile cultures) without prophylactic antibiotics was then performed with the same uneventful postoperative course. This study therefore indicates that even in the presence of bacterobilia elective cholecystectomy can be safely performed without subhepatic space drainage and without prophylactic antibiotics. PMID- 2197838 TI - The pathognomonic cytologic picture of rheumatoid pleuritis. The 1989 Maurice Goldblatt Cytology award lecture. AB - Patients with rheumatoid arthritis of any degree of severity or duration may develop necrotizing granulomatous pleuritis, a morphologic replica of the inflammatory reaction characteristic of rheumatoid synovitis and rheumatoid nodules. The ensuing pleural effusion may show a unique cytologic picture consisting of slender, elongated multinucleated macrophages, round giant multinucleated macrophages and necrotic background material. A review of 24 such cases from our laboratory as well as the relevant literature clearly demonstrated that not only is this cytologic picture unique, but that it is pathognomonic of rheumatoid disease, even in patients who have not yet developed arthritis. PMID- 2197839 TI - Myeloma with involvement of the serous cavities. Cytologic and immunochemical diagnosis and literature review. AB - The significance of serous cavity involvement by myeloma was evaluated in two patients with pleural involvement and two with peritoneal involvement. The involvement occurred at presentation in two patients and after the diagnosis of myeloma in two. The effusions were bloody exudates containing numerous atypical plasma cells. The diagnosis of cavitary involvement was made by morphologic examination of air-dried smears of the effusions, supplemented by the immunocytochemical demonstration of monoclonal proliferation of the plasma cells. In all four cases, these cells contained cytoplasmic kappa light chain immunoglobulins; many of them also stained positively for epithelial membrane antigen. It was best to interpret these immunocytochemical findings with those of the morphologic and additional immunocytochemical studies; the best results for studies for cytoplasmic immunoglobulins were obtained only if the cells in the effusions were washed before they were used for smear preparations and staining. The four patients responded poorly to treatment, dying 12 days, 16 months, 1 month and 10 days after cavitary involvement was recognized. Review of the literature confirmed that the findings in these cases were similar to those in other cases. Cavitary involvement by myeloma carries an ominous prognosis; an accurate recognition of the plasma cells by morphologic and immunocytochemical studies provides the best method of diagnosing cavitary involvement of myeloma and of predicting the poor outcome in such patients. PMID- 2197840 TI - Distinction between carcinoma cells and mesothelial cells in serous effusions. Usefulness of immunohistochemistry. AB - The usefulness of an immunoperoxidase battery to distinguish carcinomatous from benign effusions was examined. Cell block sections from 90 previously diagnosed effusions were stained with antibodies to Leu-M1, B72.3, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA) and vimentin. The 90 cases comprised 69 carcinomas (23 mammary, 16 ovarian, 10 pulmonary, 7 gastrointestinal [GI] and 13 others), 2 malignant mesotheliomas and 19 cases with reactive mesothelial cells only. EMA and vimentin were the most useful markers for distinguishing carcinoma cells from reactive mesothelial cells. EMA reacted with 86% of the carcinomas while vimentin reacted with 90% of the reactive cases. Leu M1, B72.3 and CEA, although generally less sensitive than EMA, were also helpful in this regard. Additionally, the use of Leu-M1 and CEA together may help to distinguish pulmonary from GI carcinomas. PMID- 2197841 TI - Cytologic findings in multicystic peritoneal mesothelioma. AB - The cytologic findings in a case of multicystic peritoneal mesothelioma are presented. A 70-year-old man had a slowly enlarging and intermittently painful abdominal mass that was multicystic and avascular on radiologic evaluation. Percutaneous drainage of the mass was performed over a four-year period for symptomatic relief. Large sheets of benign mesothelial cells were consistently present in the cytologic preparations of each of the drainage specimens. The mass has remained localized to the abdomen, and the patient is alive and well seven years after the onset of symptoms. The radiologic features and the clinical course of the patient were most suggestive of a rare benign multicystic peritoneal mesothelioma; the cytologic findings supported this diagnosis. A review of the pertinent literature is presented. PMID- 2197842 TI - Identification of adenocarcinoma in effusions: a comparison of immunoperoxidase staining for monoclonal antibody B72.3 and carcinoembryonic antigen. PMID- 2197843 TI - Diagnosis of two childhood cases of T lymphoblastic lymphoma by immunocytochemical study of pleural fluid. PMID- 2197844 TI - Diagnosis of Pneumocystis carinii in sputum samples using a modified toluidine blue O method. PMID- 2197846 TI - The development of intimate relationships in late adolescence. AB - Adolescence is a time of burgeoning social relationships. Further, adolescents begin to develop the capacity to be intimate. Yet, little attention has been paid to the development of intimacy in adolescence. In this paper, relationship maturity, a developmental conception of intimacy, is presented as a unifying conceptual framework for understanding these intimate involvements as part of a major developmental process. Relevant empirical literature is reviewed. Issues addressed include: specific contexts of intimacy in adolescence, the role of gender in intimacy development, the interplay of identity and intimacy development, and the effects of social issues on this process. PMID- 2197845 TI - Effect of one year continuous subcutaneous infusion of a somatostatin analogue, octreotide, on early retinopathy, metabolic control and thyroid function in Type I (insulin-dependent) diabetes mellitus. AB - Growth hormone is assumed to be involved in the development of diabetic retinopathy. In a randomized study we evaluated the possible effects of one year treatment with a somatostatin (SRIH) analogue, octreotide, on early retinopathy and on metabolism in Type I (insulin-dependent) diabetes mellitus. Eleven patients were allocated to treatment with a continuous sc infusion of 400 micrograms octreotide per day and 9 served as controls. Only 7 patients from each group completed the study. Three octreotide-treated patients left the study owing to severe diarrhea. The subjects were evaluated at entry, after 2, 6 and 12 months treatment, and 2 months after withdrawal. Octreotide induced a decrease in GH secretion, expressed as the area under the 24 h serum GH profiles (p less than 0.05), and of the serum levels of IGF-I (p less than 0.05). The entire decline in GH levels occurred during the daytime, whereas the nocturnal levels were unaffected. Retinopathy, as assessed by determination of the blood retina barrier permeability, by colour fundus photography, and flurescein angiography was unchanged in both groups. Apart from a decline in insulin requirements, octreotide had no major effect on glycemic control, but induced a mild transient pituitary hypothyroidism, not clinically relevant. We conclude that treatment with octreotide for one year has modest effects on GH, IGF-I, and glucose metabolism, but has no significant effect on early retinopathy in Type I (insulin dependent) diabetes. PMID- 2197847 TI - In pride and anxiety. PMID- 2197848 TI - Evaluation of vitamin A toxicity. AB - Toxicity has been associated with abuse of vitamin A supplements and with diets extremely high in preformed vitamin A. Consumption of 25,000-50,000 IU/d for periods of several months or more can produce multiple adverse effects. The lowest reported intakes causing toxicity have occurred in persons with liver function compromised by drugs, viral hepatitis, or protein-energy malnutrition. Certain drugs or other chemicals may markedly potentiate vitamin A toxicity in animals. Especially vulnerable groups include children, with adverse effects occurring with intakes as low as 1,500 IU.kg-1.d-1, and pregnant women, with birth defects being associated with maternal intakes as low as approximately 25,000 IU/d. The maternal dose threshold for birth defects cannot be identified from present data. An identifiable fraction of the population surveyed consumes vitamin A supplements at 25,000 IU/d and a few individuals consume much more. beta-Carotene is much less toxic than vitamin A. PMID- 2197849 TI - Validation of bioelectrical-impedance analysis as a measurement of change in body composition in obesity. AB - The bioelectrical-impedance-analysis (BIA) method accurately measures body composition in weight-stable subjects. This study validates the use of BIA to measure change in body composition. Twelve obese females underwent weight loss at a mean rate of 1.16 kg/wk. Body composition was measured by deuterium oxide dilution (D2O), BIA, and skinfold anthropometry (SFA) at baseline and at 5% decrements in weight. Highly significant correlations were obtained between D2O and BIA (r = 0.971) and between D2O and SFA (r = 0.932). Overall, BIA predicted change in fat-free mass with greater accuracy (to 0.4 kg) and precision (+/- 1.28 kg) than did anthropometry (to 0.8 kg and +/- 2.58 kg, respectively). We conclude that BIA is a useful clinical method for measuring change in body composition. PMID- 2197850 TI - Do obese individuals gain weight more easily than nonobese individuals? AB - A review of studies done on human subjects who were overfed under controlled conditions for periods ranging from 2 to 12 wk shows that the energy cost of induced weight gain is a function of initial body weight and of lean body mass, body fat, and percent body fat. Therefore, bigger and fatter people need to eat more to gain a given amount of weight than do those who are thin. A likely explanation is that obese individuals tend to put on a large proportion of fat, a high-energy tissue, whereas thin people tend to gain more lean, which is a low energy tissue. PMID- 2197851 TI - Metabolic response to glucose ingested with various amounts of protein. AB - Seven healthy, normal-weight subjects were fed breakfasts of 50 g protein, 50 g glucose, and 10, 30, or 50 g protein plus 50 g glucose in random sequence. Plasma glucose, insulin, C peptide, glucagon, nonesterified fatty acids, and alpha-amino nitrogen were then measured from samples obtained over 4 h. The postmeal net area of each response curve was calculated. Ingestion of 50 g protein alone did not change the serum glucose concentration. The various amounts of protein ingested with 50 g glucose also did not alter the serum glucose response compared with that observed with 50 g glucose alone. Ingestion of the various amounts of protein also did not result in a further increase in insulin concentration when ingested with glucose, except with the 50-g-protein dose. This increase was modest. Ingestion of glucose resulted in a decrease in alpha-amino nitrogen and glucagon concentrations whereas ingestion of protein increased them as expected. Additions of progressively larger amounts of protein to the glucose meal resulted in a progressive increase in the alpha-amino-nitrogen- and glucagon-area responses. The relationship was curvilinear for both the alpha-amino-nitrogen response and the glucagon response. The null point, that is, the protein dose ingested with 50 g glucose at which there would be no change in area response, was estimated to be 9 g protein for alpha-amino nitrogen and 5 g protein for glucagon. PMID- 2197852 TI - Effect of sucrose on the metabolic disposition of aspartame. AB - Twelve normal adult subjects ingested a beverage providing 0.136 mmol aspartame/kg body wt on 2 different days. On 1 study day the beverage provided only aspartame, on the other the beverage provided both aspartame and 3.51 mmol sucrose/kg body wt. The high mean plasma phenylalanine concentrations were similar after administration of aspartame alone (158 +/- 28.9 mumol/L, mean +/- SD) and administration of aspartame plus sucrose (134 +/- 44.1 mumol/L). Evaluation of the area under the plasma concentration-time curve (AUC) for phenylalanine also showed no significant difference between groups (197 +/- 49.1 vs 182 +/- 28.3 mumol.L-1.h for aspartame alone and aspartame plus sucrose, respectively). Similarly, the high mean ratio of phenylalanine to large neutral amino acids (Phe:LNAA) in plasma did not differ significantly (0.265 +/- 0.046 for aspartame alone, 0.275 +/- 0.107 for aspartame plus sucrose). However, there was a small but significant difference between groups for the 4-h AUC values for plasma Phe:LNAA. The simultaneous ingestion of sucrose with aspartame had only minor effects on aspartame's metabolic disposition. PMID- 2197853 TI - Duodenum-preserving resection of the head of the pancreas in treatment of chronic pancreatitis. AB - Twenty-four patients underwent duodenum-preserving resection of the head of the pancreas for chronic pancreatitis of the head. All patients were reassessed in our follow-up clinic. Comparison with partial duodenopancreatectomy showed that both procedures can alleviate the majority of symptoms. However, duodenum preserving resection of the head of the pancreas has lower early and late postoperative complication rates. It facilitates occupational rehabilitation, does not alter the patients glucose metabolism, and leaves fewer patients symptomatic in long-term follow-up. A higher rate of recurrence of pancreatitis of the tail is not found. Duodenum-preserving resection of the head of the pancreas is thus considered to be an alternative to partial duodenopancreatectomy in treatment of severe chronic pancreatitis of the head. PMID- 2197854 TI - Successful short-term medical management of an elderly man with Caroli's disease. PMID- 2197855 TI - Congenital hypoplasia of the dorsal pancreas: with special reference to duodenal papillary dysfunction. AB - We report a case of dorsal pancreatic hypoplasia complicated with atresia of the vagina, type-A chronic atrophic gastritis, duodenal papillary dysfunction, and insulin-requiring diabetes mellitus, in a 32-yr-old woman. The laboratory data showed elevated hepatobiliary enzymes. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a slightly dilated common bile duct and a short major pancreatic duct connected with a minor pancreatic duct. Ultrasonography and computerized tomography could not identify any pancreatic tissue in the region of the body or tail of the pancreas. The pancreatic tissue weight calculated by the serial thin slice of computerized tomography was 43.1 g, approximately 45% of the standard Japanese adult pancreas. Reevaluated pancreatic exocrine function based on this weight showed a hypersecretory state. The pancreatic ductal pressure was slightly increased, and the motility of the sphincter of Oddi (SO) was abnormal when measured with a 4Fr. microtransducer inserted through a duodenoscope. These findings suggest that dysfunction of the sphincter of Oddi may play some role in the pathophysiology in the hypoplasia of the dorsal pancreas and pancreaticobiliary diseases associated with it. PMID- 2197856 TI - Recurrent massive upper gastrointestinal hemorrhage due to Strongyloides stercoralis infection. AB - A 29-yr-old black male immigrant from Africa presented with recurrent life threatening upper gastrointestinal bleeding due to massive duodenal infection by Strongyloides stercoralis. The diagnosis was missed by repeated examinations of fresh stool specimens for ova and parasites and by an initial esophagogastroduodenoscopy. The diagnosis was made by pathologic examination of a duodenal biopsy and of a duodenal aspirate obtained at a second esophagogastroduodenoscopy. This has been previously reported as a cause of massive upper gastrointestinal hemorrhage in four cases. Patients with obscure gastrointestinal bleeding who have travelled or lived in an endemic area should have a duodenal aspiration performed at esophagogastroduodenoscopy. PMID- 2197857 TI - Duodenal obstruction: a complication of percutaneous endoscopic gastrostomy tube migration. AB - Percutaneous endoscopic gastrostomy (PEG) is now a well-established technique for providing long-term enteral feeding. The procedure is being increasingly utilized and, although generally well tolerated, it may be associated with complications. We report two patients in whom a replacement Foley balloon tip catheter migrated into the small bowel and caused obstruction. The diagnosis, management, and preventive measures of tube migration are discussed. PMID- 2197858 TI - The peritoneovenous shunt: expectations and reality. AB - Since the introduction of the LeVeen modification of the peritoneovenous shunt (PVS) in 1974, these devices have been placed in a relatively large number of patients. The most common indication has been for medically intractable ascites in the setting of chronic liver disease. A review of a series of studies shows that we can expect approximately an 18% perioperative overall mortality rate, a 46% survival rate at 21 months, and loss of ascites in 59% of the survivors at 18 months. The PVS has not been shown by prospective trials to prolong survival significantly in patients with either intractable ascites or the hepatorenal syndrome (HRS), although it may shorten hospitalizations, compared with medical controls. A few well-documented cases of reversal of the HRS have been documented. The best results of PVS therapy have been evident in those patients with milder liver disease. The loss of ascites need not correlate with a functioning shunt. Alcohol abstinance is associated with hepatic functional recovery and may relate to the disappearance of renal sodium retention, resulting in shunt occlusion due to low flow. A number of serious complications with the PVS have been described. Nutritional repletion follows successful shunting, but might, in part, relate to simultaneous alcohol abstention. The more common complications of coagulopathy and fluid overload are preventable by total ascitic drainage at the time of surgery. Shunt patency remains a clinical problem. Only 18.6% of the total shunts placed functioned in the survivors at 2 yr. Perioperative infections with staphylococcal and Gram-negative organisms occur. Postoperative bacterial peritonitis or septicemia requires shunt removal for cure. PMID- 2197859 TI - Eroded polypoid hyperplasia of the rectosigmoid. AB - We studied histologic sections and clinical data from six patients with multiple rectosigmoid polyps that could not be readily classified. Features common to all were: 1) numerous polyps restricted to the rectosigmoid colon without evidence of polyposis or gastrointestinal disease elsewhere, 2) severe clinical symptoms mimicking inflammatory bowel disease, 3) no family history of polyposis or evidence of infection and 4) histology showing minimally inflamed polypoid hyperplastic mucosa with surface erosions or pseudomembranes. Three patients underwent colectomies; three showed a response to oral steroids. One had rectal prolapse. Although reminiscent of inflammatory cloacogenic polyps or solitary rectal ulcer syndrome, the polyps extended into the sigmoid colon, were quite numerous, and showed only mild smooth muscle insinuation in the lamina propria. Whether these lesions are due to occult prolapse or are an unusual manifestation of inflammatory bowel disease remains unclear. PMID- 2197860 TI - A comparison of tocolysis with nifedipine or ritodrine: analysis of efficacy and maternal, fetal, and neonatal outcome. AB - Nifedipine, a dihydropyridone calcium entry blocker, has been used with increasing frequency in the treatment of preterm labor. We studied 66 patients in this prospective, randomized trial to evaluate the efficacy and maternal, fetal, and neonatal outcome associated with tocolysis with nifedipine or ritodrine. Delivery was delayed for 48 hours, 7 days, and until the thirty-sixth week of gestation in 84%, 70%, and 41%, respectively, of patients in the nifedipine group, compared with 72%, 63%, and 52% of patients in the ritodrine group (difference not significant). Maternal side effects were more common and more serious in the group of patients who received ritodrine compared with those who received nifedipine (18 of 38 versus 5 of 38, p less than 0.01); however, fetal and neonatal outcome appeared to be similar when the groups were compared. On the basis of this study, it appears that tocolysis with either nifedipine or ritodrine is equally efficacious; however, maternal side effects are less common with nifedipine treatment. We conclude that nifedipine may have a role in the treatment of preterm labor but suggest further careful evaluation of this agent before it is considered for routine clinical use. PMID- 2197861 TI - Endometrial assessment by vaginal ultrasonography before endometrial sampling in patients with postmenopausal bleeding. AB - Endometrial sampling is the mainstay of management of the postmenopausal patient with uterine bleeding. Thirty women with postmenopausal bleeding were studied prospectively. Before endometrial sampling, a vaginal probe ultrasonographic examination was performed. Eleven patients demonstrated a thin "pencil line" endometrial echo in which the maximum anteroposterior thickness on the long axis view was less than or equal to 5 mm. All eleven patients had minimal tissue obtained on biopsy and a pathology report of "tissue insufficient for diagnosis." Seventeen patients had an echogenic endometrium greater than or equal to 6 mm. Pathology reports of their samples revealed tissue insufficient for diagnosis (two cases), proliferative endometrium (six), secretory endometrium (three), hyperplastic endometrium (three), polyp (two), and endometrial cancer (one case). Two additional patients had no endometrial echo visualized because of associated myomas. These findings suggest (1) that the absence of significant endometrial tissue (echo less than or equal to 5 mm) on vaginal ultrasonography in cases with postmenopausal bleeding is uniformly associated with tissue insufficient for diagnosis, and (2) when endometrial thickness is greater than or equal to 6 mm the histologic diagnosis should be determined in the pathology laboratory. PMID- 2197862 TI - Transabdominal and transvaginal ultrasonography in the diagnosis of ectopic pregnancy: a comparative study. AB - Thirty-four patients believed to have ectopic pregnancies were examined by transabdominal and transvaginal ultrasonography. Twenty-five patients had tubal pregnancy confirmed operatively within 24 hours after ultrasonographic examination. In these cases adnexal findings highly suspicious for ectopic pregnancy were found in 68% of cases by transabdominal ultrasonography and in 84% by transvaginal ultrasonography. A distinct adnexal gestational sac was apparent in 32% of cases by transabdominal ultrasonography and in 64% of cases by transvaginal ultrasonography. Transvaginal ultrasonography was significantly more accurate (p less than 0.01) in identifying an adnexal gestational sac and allows more detailed adnexal imaging. PMID- 2197863 TI - Risk factors for preterm premature rupture of fetal membranes: a multicenter case control study. AB - To assess the association between women with preterm premature rupture of membranes and 41 potential risk factors, we conducted a case-control study in six United States tertiary perinatal centers. The study involved completion of a comprehensive questionnaire for 341 women with preterm premature rupture of membranes in singleton pregnancies from 20 to 36 weeks' gestation and 253 control women matched for maternal age, gestational age, parity, clinic or private patient status, and previous vaginal or cesarean delivery. Univariate analysis revealed 11 variables associated with a significantly (p less than 0.05) increased risk of preterm premature rupture of membranes. After multiple logistic regression analysis, three variables remained in the model as independent risk factors: antepartum vaginal bleeding in more than one trimester (odds ratio 7.4; 95% confidence interval, 2.2, 25.6), current cigarette smoking (odds ratio, 2.1; 95% confidence interval, 1.4, 3.1), and previous preterm delivery (odds ratio, 2.5; 95% confidence interval, 1.4, 2.5). Cessation of cigarette smoking by pregnant women may reduce the risk of preterm premature rupture of membranes. Further study is necessary to determine the nature of the relationship between antepartum vaginal bleeding and preterm premature rupture of membranes. PMID- 2197864 TI - Changes in platelet angiotensin II binding sites associated with the human menstrual cycle. PMID- 2197865 TI - Risk factors for perinatal group B streptococcal disease after amniotic fluid colonization. AB - A group of 1031 parturient women at high risk for intraamniotic infection were studied. Women in whom group B streptococci grew from cultures of the amniotic fluid did not differ in clinical risk factors when compared with similar parturient women without group B streptococcal colonization of amniotic fluid. Patients who had perinatal group B streptococcal disease (maternal or neonatal bacteremia) did not differ from those without disease, by maternal or neonatal acute antibody levels or antibody response, inoculum size, or serotype of the colonizing strain. PMID- 2197867 TI - Relationship between the ovine fetal umbilical artery blood flow waveform and umbilical vascular resistance. AB - Ultrasonic umbilical artery blood flow velocity waveform indexes decrease throughout gestation as umbilical blood flow increases. However, it is not known whether the decrease in indexes such as systolic/diastolic ratio is a direct result of a change in umbilical vascular resistance. Umbilical artery blood flow was measured as vasoactive agents angiotensin II, arginine vasopressin, norepinephrine, serotonin, and the thromboxane A2 sympathomimetic agent U-46619 were infused into the inferior vena cava of chronically instrumented ovine fetuses. Angiotensin II, arginine vasopressin, norepinephrine, serotonin, and U 46619 all significantly increased fetal arterial pressure levels. Angiotensin II, arginine vasopressin, and U-46619 significantly reduced umbilical blood flow and fetal heart rate. All five pressor agents increased umbilical vascular resistance. Systolic/diastolic ratios were obtained from pulsatile umbilical blood flow tracings. Systolic/diastolic ratios before infusions were significantly correlated with baseline values of umbilical blood flow (r = -0.55) and umbilical vascular resistance (r = 0.52). Systolic/diastolic ratios decreased with increasing infusion rates of angiotensin II, arginine vasopressin, norepinephrine, and serotonin, and increased with infusion of U-46619. There was no significant correlation between systolic/diastolic ratio and either umbilical blood flow or umbilical vascular resistance during infusion of angiotensin II, arginine vasopressin, or serotonin. Systolic/diastolic ratio decreased with increasing umbilical vascular resistance during norepinephrine infusion (r = 0.44). Systolic/diastolic ratio changed in the predicted direction only when umbilical vascular resistance was increased by infusion of U-46619 (r = 0.80). We conclude that umbilical artery waveform analysis is not an adequate predictor of acute changes in umbilical blood flow or vascular resistance. PMID- 2197866 TI - Immunoglobulin G fractions from patients with antiphospholipid antibodies cause fetal death in BALB/c mice: a model for autoimmune fetal loss. AB - We determined whether purified immunoglobulin G from patients with antiphospholipid antibodies causes fetal loss in pregnant mice. Sera were obtained from nonpregnant parous women (group 1) and nonpregnant women with antiphospholipid antibodies and a history of fetal loss (group 2). Pregnant BALB/c mice were given an intraperitoneal injection of 15 mg of IgG on day 8 of pregnancy. Typically, mice treated with IgG from antiphospholipid antibodies aborted within 48 hours. When animals were sacrificed on days 9 to 15, the uterus of each animal was inspected for the presence of live, dead, or resorbing fetuses. In contrast to mice injected with control IgG or saline solution, each mouse injected with IgG from antiphospholipid antibodies aborted and no live fetuses were found (p less than 0.05). Histologic examination of the uteroplacental interface showed decidual necrosis in the mice treated with IgG containing antiphospholipid antibodies, and immunofluorescent studies also showed prominent intravascular decidual IgG and fibrin deposition. We conclude that IgG from antiphospholipid antibodies of women with fetal loss causes fetal loss in BALB/c mice. It appears that the fetal loss is mediated by IgG binding in the maternal decidual vasculature. PMID- 2197868 TI - Accuracy of apical four-chamber view as screen for congenital heart disease. PMID- 2197869 TI - Blood flow velocity and pulsatile diameter changes in the fetal descending aorta: a longitudinal study. AB - Blood flow velocity and pulsatile diameter changes in the fetal descending aorta were measured subsequently with pulsed Doppler ultrasonography and phase-locked echo-tracking technique, respectively. Blood flow velocity and pulse-wave curves with equal beat-to-beat intervals were synchronized by external fetal electrocardiogram. The systolic increase in blood flow velocity and in vessel diameter started simultaneously. The velocity peak preceded the diameter peak by a significant margin (p in the range 0.0001 to 0.0014). The time interval was more pronounced in the thoracic than in the abdominal part of the aorta and was slightly smaller near term. The effective diameter, calculated from the synchronized integrals of the blood flow velocity and the diameter curves, was significantly greater (p in the range 0.0001 to 0.0016) than the mean diameter. The difference tended to decrease with advancing gestational age and was more pronounced in the thoracic than in the abdominal aorta. The maximum error incurred by the use of nonsimultaneous measurements of blood flow velocity and vessel diameter when calculating volume blood flow was found to be less than 8% and thus probably of little practical importance. PMID- 2197870 TI - Study results vary in count-to-10 method of fetal movement screening. PMID- 2197871 TI - How sperm commence movement and their isolation for in vitro fertilization and sex selection. PMID- 2197872 TI - Blood pressure measured telemetrically from home throughout pregnancy. AB - Sixty-eight healthy pregnant women measured their blood pressure at home for 1 day every 4 weeks from 14 weeks' gestation until delivery. Blood pressure measurements were made with the Cambridge blood pressure telemetry system, which was composed of a Dinamap 1846 monitor linked to and controlled by a dedicated microprocessor which communicated transtelephonically with a hospital-based microcomputer. On each measurement day each woman measured her blood pressure five times: on first rising and then at 10 AM, 2 PM, 6 PM and 10 PM. At each measurement session the blood pressure was automatically taken 10 times at 1 minute intervals. A total of 23,790 individual blood pressure measurements were analyzed. Systolic, diastolic, and mean arterial blood pressures were lowest at 18 weeks' gestation, rising slowly thereafter at a rate of 0.4 mm Hg systolic and 0.2 mm Hg diastolic per week. The maternal pulse rate also increased steadily after 18 weeks at a rate of 0.25 beats/min per week. There was a strong correlation between the blood pressures at 18, 26, and 38 weeks. All blood pressure parameters were significantly lower on first rising than at other times of the day, although the differences were small: 5 mm Hg for systolic, 4 mm Hg for mean arterial, and 3 mm Hg for diastolic blood pressure. After 10 AM, however, there was no significant daytime variation in any blood pressure parameter, indicating that for most purposes the time of day at which pressure measurements are made is unimportant. PMID- 2197873 TI - Systemic cystic angiomatosis in pregnancy: a case presentation and review of the literature. AB - Systemic cystic angiomatosis is the involvement of multiple organ systems with a congenital vascular malformation. A combination of vascular anomalies, namely lymphangioma and hemangioma, can coexist. The liver, spleen, kidney, and colon are the most commonly affected organs. The clinical presentation varies and generally reflects the involved organ system. A case of systemic cystic angiomatosis involving the spleen, liver, and kidney is presented. The diagnosis and management during pregnancy is discussed. PMID- 2197874 TI - In utero detection of cardiac failure from an aneurysm of the vein of Galen. AB - The detection of a vein of Galen aneurysm in a hydrocephalic fetus is presented. The differential diagnosis for the midline cystic structure was made on the basis of the presence of high-velocity flow on Doppler ultrasonographic examination. PMID- 2197875 TI - Indomethacin treatment for polyhydramnios and subsequent infantile nephrogenic diabetes insipidus. AB - A case of polyhydramnios was effectively treated with amniotic fluid decompression and indomethacin. Six months later nephrogenic diabetes insipidus was diagnosed and indomethacin was again effectively used. By reducing urine output, indomethacin controlled both in utero and extrauterine polyuria in this patient. PMID- 2197876 TI - A nonracial craniofacial perspective on human variation: A(ustralia) to Z(uni). AB - Dental and craniofacial measurements were collected for 57 samples from Asia, the Pacific, the aboriginal western hemisphere, and Europe. The craniofacial dimensions include many that are not obviously under the control of specific selective forces. Similar configurations for these in different samples should yield indications of recency of common ancestry according to the logic expressed by Darwin and evident in the relationships indicated by nuclear DNA comparisons. Dental dimensions, however, vary according to the length of time that different intensities in selective forces have been in operation. The craniofacial measurements were transformed into C scores and used to generate Euclidean distance dendrograms. When all the material was used to generate a single dendrogram, the European and Amerindian samples sorted into two regionally identifiable clusters, and the Asian and Pacific material sorted into the three clusters identified in separate previous studies: a Mainland Asian cluster, a Jomon-Pacific cluster and an Australo-Melanesian cluster. Since these clusters are based on variation in traits that are basically nonadaptive in nature, no hierarchical ranking is possible. The clusters simply reflect degree of relationship. This technique holds forth the promise of producing a nonracial assessment of the relationships of all the peoples of the world, past and present. PMID- 2197877 TI - Periodontal defects of pulpal origin: evidence in early man. AB - False assumptions have led to the widespread opinion that periodontitis of gingival origin is a ubiquitous disease and a common cause of tooth loss among ancient populations. Evaluation of dry skulls reveals that horizontal loss of crestal alveolar bone was unusual and of minor severity. Localized vertical bone defects of pulpal etiology were common and severe, often resulting in tooth mortality. The present paper identifies a number of factors that have contributed to the development of some important misconceptions about the nature of periodontal disease, its incidence, and its etiology. PMID- 2197878 TI - Characterization of the macula densa stimulus for renin secretion. AB - These studies utilize the isolated perfused rabbit juxtaglomerular apparatus (JGA) to study the macula densa signal for renin secretion in the absence of the confounding influences of intravascular pressure and renal nerve activity. In the first experimental series, JGAs were perfused alternately with high- and low-NaCl solutions to determine the reversibility of the renin response to changes in NaCl concentration. Compared with high-NaCl controls, perfusion with a low-NaCl solution resulted in a fivefold increase in renin secretion rate (RSR) [2.1-10.0 nano-Goldblatt hog units (nGU)/min], and this response was largely reversible. When the solutions were presented in the reverse order, a similar inhibition by high NaCl was observed. In the second series, JGAs were perfused with high-, medium-, and low-NaCl solutions to determine the sensitive range of the renin response to NaCl concentration changes. The full renin response (3.2-16.6 nGU/min), similar in magnitude to that seen in series 1, was found to occur between 80 and 24 mM for Na+ and 61 and 7 mM for Cl-. In the third series, the NaCl concentration and flow rate of the perfusate were altered independently to separate the effects of flow rate, NaCl delivery, and NaCl concentration on RSR. Although a decrease in perfusate flow rate slightly increased RSR (3.4-8.1 nGU/min), a comparable decrease in NaCl concentration resulted in a much higher RSR (26.3 nGU/min). We conclude that in this preparation 1) RSR responds equally to both increases and decreases in macula densa NaCl concentration, and these changes are rapid and largely reversible, 2) the full renin response occurs within the concentration range normally occurring at the macula densa, i.e., below 80 mM Na+ and 61 mM Cl-, and 3) RSR responds with a larger change to alterations in NaCl concentration than in NaCl delivery or fluid flow rate. PMID- 2197879 TI - Plasma profiles of IL-6 and TNF with fever-inducing doses of lipopolysaccharide in dogs. AB - This study was designed to test the tumor necrosis factor (TNF) WEHI 164 clone 13 bioassay and the interleukin 6 (IL-6) B9 bioassay for sensitivity to endogenously produced dog TNF and IL-6 and then to use these assays to examine the associations between these cytokines and lipopolysaccharide (LPS)-induced fever. When dogs were injected with LPS (40, 10, 1, 0.1, and 0.01 microgram/kg), the resulting fever was dose dependent. A plot of plasma cytokine changes over time following LPS injections showed that the plasma TNF-like activity appeared to increase in an all-or-none dose response, whereas the increase in plasma IL-6 like activity appeared to be log dose dependent. Plasma TNF-like and IL-6-like activity were then separately plotted against temperature change (fever). Statistical analysis supported the interpretation that both TNF-like and IL-6 like activity were related to LPS-fever in an all-or-none manner, with IL-6 having a threshold region. We conclude that if these cytokines are circulating mediators of fever, they may induce fever in an all-or-none fashion. PMID- 2197880 TI - Reduced adipsin mRNA and circulating adipsin protein are modulated by adrenal steroids in obese Zucker rats. AB - We investigated expression of the adipose-specific serine protease adipsin in genetically obese Zucker rats and whether adrenalectomy modifies expression. Adipsin mRNA levels were determined by slot blot and Northern blot analysis of total RNA samples extracted from epididymal adipose tissue and isolated retroperitoneal adipocytes of obese (fa/fa) and homozygous lean (Fa/Fa) Zucker rats. Both 30-day-old and 4-mo-old animals were analyzed in experiment 1. In experiment 2, 10-wk-old obese and lean rats were either bilaterally adrenalectomized or sham operated, and adipsin mRNA levels were determined on tissue and cell samples 2 wk postsurgery. In both experiments, serum adipsin protein was determined by Western blot analysis and plasma insulin by radioimmunoassay. The data show that both adipsin mRNA and adipsin protein are reduced in obese compared with lean rats and that adrenalectomy restores these values toward normal in obese rats. The data thus suggest that adrenal steroids are involved in modulating adipsin expression in obese Zucker rats and that insulin may be an intermediary factor in such modulation. PMID- 2197881 TI - Effect of intrarenal renin inhibition on renal hemodynamics and excretory function. AB - This study was designed to investigate in sodium-depleted monkeys the renal hemodynamic and excretory effects resulting from blockade of the renin angiotensin system induced by intrarenal infusion of the primate-selective renin inhibitor A-65317. Intrarenal infusion of A-65317 (n = 6) at a dose of 0.01 micrograms.kg-1.min-1 elicited an increase (P less than 0.05) in renal blood flow (RBF) from 43.5 +/- 2.7 to 49.4 +/- 4.4 ml/min and glomerular filtration rate (GFR) from 6.3 +/- 0.3 to 6.9 +/- 0.4 ml/min, with no significant changes in mean arterial pressure (MAP) or plasma renin activity (PRA). Increases (P less than 0.05) in the urine flow rate (0.18 +/- 0.04 to 0.28 +/- 0.04 ml/min) and the fractional excretion of sodium (0.18 +/- 0.06 to 0.35 +/- 0.13%) were also observed. After a recovery period, the intrarenal infusion dose of A-65317 was increased to 0.1 microgram.kg-1.min-1 and RBF increased (P less than 0.05) from 42.9 +/- 3.9 to 53.0 +/- 3.7 ml/min in conjunction with a significant 85 +/- 4% inhibition of PRA and a 14 +/- 4 mmHg reduction in MAP. GFR and electrolyte excretion remained at control levels. Intrarenal infusion of vehicle (n = 6) had no significant effect on any of the variables studied. In a separate group of monkeys, intravenous (iv) infusion of A-65317 at 0.01 microgram.kg-1.min-1 (n = 5) did not result in significant changes from control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2197882 TI - A comparison of manual and MEDLARS reviews of the literature on consultation liaison psychiatry. AB - A systematic manual search for articles related to consultation-liaison psychiatry was compared to a computerized search of the same journals during the same period that was done with the Medical Literature Analysis and Retrieval System (MEDLARS). More articles were located with the manual method (94%) than with MEDLARS (65%). PMID- 2197883 TI - Validity of the Personality Diagnostic Questionnaire--revised: comparison with two structured interviews. AB - The authors gave the self-report Personality Diagnostic Questionnaire--Revised (PDQ-R) to 87 applicants for inpatient treatment of severe personality psychopathology and, blind to these results, diagnosed personality disorders in the applicants by using the Personality Disorder Examination and the Structured Clinical Interview for DSM-III-R Personality Disorders. The PDQ-R was not a substitute for a structured interview assessment of axis II disorders because many of its diagnoses were false positives. Its high sensitivity and moderate specificity for most of the axis II disorders suggest, however, that it is an efficient instrument for screening patients with DSM-III-R personality disorders. PMID- 2197884 TI - Freud's major case histories. PMID- 2197885 TI - Utilization management of mental health services by private third parties. AB - The author describes approaches to utilization management and the growth of this segment of the health care industry. Issues posed for the mental health field by introducing a third party as the arbiter of care include professional uncertainty and the discretionary behavior of practitioners and third parties, the availability of clinically appropriate alternative services, shifting of costs between the public and private sectors, safeguarding privacy, accountability and the integrity of the review process, financial risk versus professional responsibility, and the impact of utilization management on the outcome of care. PMID- 2197886 TI - The relation of ulcerative colitis to psychiatric factors: a review of findings and methods. AB - The authors reviewed all known English-language literature on the association between psychiatric factors and ulcerative colitis to ascertain the evidence for such an association and evaluate the methods used in these studies. Most of the 138 studies contained serious flaws in research design, such as lack of control subjects, unspecified manner of data collection, and absence of diagnostic criteria. Analysis revealed that methodological flaws were significantly related to the finding of a positive association between psychiatric factors and ulcerative colitis. Seven studies represented solid systematic investigation, and all seven failed to find such an association. PMID- 2197887 TI - [Mechanisms of drug metabolism in the feto-placental system]. PMID- 2197888 TI - [Prognostic value of placental maturity staging for pregnancy outcome of the fetus and newborn infant]. AB - Prenatal ultrasonographic diagnosis in 267 pregnant women, examination of their newborns and ultrasonographic/morphological comparison of the placenta have demonstrated the value of placenta staging in the prediction of fetal and neonatal outcomes with reference to the gestational age and morphological maturity of the villous placenta. The simplicity and predictive value of these criteria make them recommendable for routine use in practical medical care. PMID- 2197889 TI - [Diagnosis of placental insufficiency in patients with acquired heart defects]. AB - The feto-placental unit has been evaluated in 102 patients with acquired heart disease presenting as different circulatory states (Grade 0 insufficiency in 43, Grade I in 34 and Grade II A-B in 25 women). Placental scintigraphy was performed in 102, cardiotocography in 77, ultrasonographic fetal and placental biometry in 102 and placental pathological examination in 15 women. The neonatal study included 104 infants, with 2 twin pairs. Scintigraphy revealed utero-placental blood flow (UPBF) impairment in 72 (70.6%) pregnancies; cardiotocography showed chronic fetal hypoxia in 51 (66.1%) and ultrasonography showed intrauterine growth retardation in 44 (43.1%) pregnancies. Disorders of UPBF coexisted with chronic fetal hypoxia and intrauterine growth retardation in 33 (42.8%) pregnancies, with chronic fetal hypoxia in 18 (23.4%) pregnancies. Impairment of UPBF alone was seen in 13 (16.9%) pregnancies. The digoxin test was done concomitantly with placental scintigraphy in 28 patients; it improved diagnostic precision and provided a measure of compensation of impaired UPBF. PMID- 2197890 TI - [Comparative evaluation of Doppler ultrasonic and cardiotocographic data in critical states of fetoplacental circulation]. PMID- 2197891 TI - [Characteristics of the course and outcome of pregnancy in developmental anomalies of the uterus]. AB - Ultrasonographic follow-up of 311 pregnant women with a history of habitual abortion has revealed uterine malformations in 61 (19.6%) women. An arcuate uterus was found in 25, bicornuate and duplex uterus in 20, septate uterus in 15 and unicornuate uterus in 1 women. The paper presents ultrasonographic criteria for the identification of uterine malformations and certain pregnancy complications. The study showed pregnancy outcomes to be correlated to malformation severity. The outcomes were satisfactory in the presence of the arcuate uterus and poor in the presence of the bicornuate and septate uterus. The findings suggest that all women with uterine malformations require a close follow up throughout the pregnancy to make an earlier diagnosis and to remedy the abnormalities detected. PMID- 2197893 TI - [Echographic dynamic control of the urinary system and fetal development in pregnant women with acute pyelonephritis]. AB - Ultrasonography in 52 pregnant women with acute pyelonephritis has been found to be a useful marker of efficacy of aggressive care. Reversal of inflammation in acute pyelonephritis without an associated disease reduced the kidney size and restored urine flow by the end of the 7-9th day of therapy. In pyelonephritis coexisting with nephrolithiasis, reversal of inflammation did not completely restore urine flow until a stone in the urinary tract was passed or surgically removed. The clinical patterns of pyelonephritis were elucidated in congenital renal malformations. The urine flow was completely restored and kidney sizes were maximally contracted postpartum. With an early therapy, the fetal development was appropriate for gestational age. Frequently relapsing pyelonephritis concomitant with toxemia or severe congenital renal disease led to intrauterine growth retardation. PMID- 2197892 TI - [Prevention of hypotonic hemorrhage in the placental and early puerperal period with prostenone]. AB - To prevent afterbirth and early postpartum hemorrhages the authors used prostenone in 46 (the main group) and oxytocin in 20 females (control group). Intraplacental blood pressure and coagulation parameters were studied. With prostenone, the mean amount of the blood loss turned to be significantly lower (137 +/- 13 ml) than with oxytocin (208 +/- 17 ml). Administration of prostenone led to a significant elevation of prothrombin index alone and tolerance to heparine. As there was an insignificant difference between the parameters in the main and control groups, the mechanism of prostenone's effect on the myometrium required further studies. PMID- 2197894 TI - [Methodologic aspects of studying the effects of ecologic factors on the reproductive system of women]. PMID- 2197895 TI - [Ultrasonic scanning in the diagnosis of threatened premature labor]. PMID- 2197896 TI - [The 60th anniversary of the Moscow District Research Institute of Obstetrics and Gynecology]. PMID- 2197897 TI - [Hormonal and immunologic interrelations in the mother-placenta-fetus system in pregnant women with pyelonephritis]. PMID- 2197898 TI - [Recovery, amnesia and affective state following propofol in comparison with thiopental]. AB - Numerous reports have described a definite sense of well-being after anesthesia with propofol (Disoprivan). The present study was designed to assess postoperative mood as recorded with a quantitative self-rating method. Postoperative recovery and amnesia were also investigated. Thirty unpremedicated female patients aged 20-60 (ASA grade 1 or 2) who were scheduled for minor gynecological operations were enrolled in the study after informed consent. The patients were randomly allocated to three study groups: group A, induction with propofol 2 mg/kg and maintenance with propofol 0.15 mg/kg per min together with N2O/O2; group B, induction with propofol 2 mg/kg and maintenance with enfluran and N2O/O2; group C, induction with thiopental until loss of the eye lash reflex and maintenance with enfluran and N2O/O2. Postoperative amnesia was assessed by showing five picture cards at 5-min intervals, starting when the patients were able to state the correct date of birth. A test of recovery (p-deletion) was carried out after 30 and again after 60 min. The postoperative mood state was evaluated with the adjective checklist of Janke and Debus 5 h after waking. In good agreement with published reports, propofol patients recovered more rapidly than thiopental patients. A significant but irrelevant amnesia occurred after 5 min in group B. However, in some cases amnesia lasting up to 20 min was observed. The global mood status showed a significantly higher score for positive items and a lower score for negative items after propofol administered by either technique than after thiopental (P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2197899 TI - [Routine throat swabs in artificially ventilated patients: meaningful bacteriologic monitoring or a needless procedure?]. AB - Organisms colonizing the oropharynx of patients in the intensive care unit (ICU) play an important role in the development of nosocomial infection. Thus, routine throat swab specimens of ICU patients are recommended to screen for potential pathogens [20]. This investigation was designed to clarify the value of throat swabs taken in addition to tracheal aspirates, urine cultures, and wound swabs with regard to antibiotic therapy in patients with pneumonia and other infections. MATERIALS AND METHODS. A total 627 intubated patients were examined in a surgical ICU during a 12 month period. Pharyngeal swabs, tracheal aspirates, urine cultures, and-if necessary-swabs from wounds and drains were taken immediately after admission to the ICU and routinely thereafter three times each week. DEFINITIONS: Early onset pneumonia: pneumonia occurring within 4 days; late onset pneumonia: pneumonia occurring after the 4th day. Intra-abdominal infection: diffuse or localized peritonitis or abdominal abscess. Wound infection: soft-tissue or bone infection. Corresponding organisms: the same species of bacteria with the same sensitivity pattern (Table 1). RESULTS. Sixty eight of the patients developed pneumonia. 37 had early onset pneumonia. In 22 of these patients, throat and tracheal specimens had been obtained 2-3 days before the pneumonia was diagnosed. In these specimens, the causative organisms for the subsequent pneumonia were isolated in the throat in 60% of cases and in tracheal secretions in 40% (Table 3). In 35 patients with late onset pneumonia, the causative bacteria were found in 66% of the cases in the throat swabs obtained 2 3 days before the diagnosis was made, in tracheal aspirates in 74% (Table 4). Throat swabs obtained at admission to the ICU from already infected patients or from patients who developed an infection were significantly more colonized with potentially pathogenic micro-organisms (Fig. 1). In 4 patients with early onset pneumonia the results of the throat swab cultures influenced antibiotic therapy, but none of the throat culture results influenced the therapy of the patients with late onset pneumonia or other infections (intra-abdominal infection, wound infection, urinary tract infection). CONCLUSIONS. The throat swab taken at admission may indicate patients at risk for infection. However, throat cultures taken routinely thereafter, parallel with tracheal aspirate cultures, do not provide additional information that is diagnostically or therapeutically helpful. Therefore, throat swab cultures are not necessary for routine bacteriological monitoring. For the prevention of colonization by local administration of antimicrobial agents, regular throat cultures are mandatory. PMID- 2197900 TI - [Gert-Horst Schumacher on his 65th birthday]. PMID- 2197901 TI - [The history of morphological research of the vascular bed of the skeletal muscles]. AB - The present paper briefly reports on the history of vascular research with special emphasis to the contribution of G. Prochaska and W. Spalteholz in the topic of the vascular pattern in the skeletal muscle. The merit of Prochaska was to summarize the findings of earlier investigators and to perform own experiments using injection techniques to demonstrate vessels in the muscle. For a longer period his results has served as the morphological base for the physiological understanding of the muscular circulation. 100 years later W. Spalteholz was the first scientist which has elaborated a complete scheme of the vascular distribution in the muscle including the capillaries, using his special method, to make tissue translucent combined with injection techniques. His fundamental work "Die Vertheilung der Blutgefasse im Muskel" was published in 1888. In many details it is valid up to recent time because the concept of Chambers and Zweifach can not be applied to the circulation of the muscle. Additionally our report gives information of further development of vascular research in the muscle with respects to theoretical problems and practical application in the muscle surgery. PMID- 2197902 TI - [The history of anatomy in Magdeburg]. PMID- 2197903 TI - The pregnant woman in the work place: potential embryopathic risks. AB - Many women of childbearing age now work in an environment that is associated with reproductive and teratogenic risks. Problems relating to the assessment and control of potential teratogenic hazards in the work place are discussed in this paper. Risk factors include industrial solvents, air pollution, water pollution, noise, anesthetic agents, and video display terminals. PMID- 2197904 TI - Elements of a general theory of joints. 1. Basic kinematic and static function of diarthrosis. AB - The kinematicaly open, dimeric link chain represents the simpliest module of a diarthrosis. The simpliest synarthrosis is represented by a (visco-)elastic disk that connects two rigid bodies. Diarthroses and synarthroses are statically distinguished by the character of force transfer. Because of their adhesive connection to the corresponding bony structures synarthroses can transfer shear stresses while diarthroses can only be loaded by forces which act normal to their functional surfaces. Therefore, the interface between the body structure and the elastic synarthrosis can be considered as a surface of infinite static (adhesive) friction, while the contacting surfaces in a diathrosis possess vanishing static friction. Kinematically, the difference between diarthroses and synarthroses is established by the fact that diarthroses possess axes of rotation which are approximately fixed relatively to the morphology of the corresponding functional surfaces while in synarthroses the positions of rotational axes depend on the geometric structure of the applied and transferred force system. The first part entire paper presents the most simple module of a diarthrosis, the kinematically open dimeric link chain. PMID- 2197906 TI - Fluconazole, a new antifungal agent. PMID- 2197905 TI - Assessment of deep venous incompetence: a prospective study comparing duplex scanning with descending phlebography. AB - In this prospective study duplex scanning was performed in 21 consecutive patients (23 lower extremities) referred for descending phlebography. The grade of deep venous insufficiency (Grades 1-4) was estimated in a blinded fashion with phlebography and duplex technique. Agreement occurred in 15 of 23 lower extremities. Discrepancies were found particularly in patients with minor degrees of reflux. The patients with reflux below the knee according to phlebography were also identified with ultrasonography. The authors found duplex scanning to be accurate method of evaluating deep venous valvular function. With duplex--but not with phlebography--it was also possible to diagnose isolated lower extremity valvular insufficiency. PMID- 2197907 TI - Pharmacoepidemiology: current status, prospects, and problems. PMID- 2197908 TI - Fluconazole compared with amphotericin B plus flucytosine for cryptococcal meningitis in AIDS. A randomized trial. AB - OBJECTIVE: To compare the efficacy of fluconazole with amphotericin B plus flucytosine in the treatment of cryptococcal meningitis. DESIGN: Patients were randomly assigned to oral fluconazole, 400 mg/d, for 10 weeks or to amphotericin B, 0.7 mg/kg body weight daily for 1 week, then three times weekly for 9 weeks combined with flucytosine, 150 mg/kg d, in four divided doses. SETTING: Los Angeles County-University of Southern California Medical Center. PATIENTS: Between 15 February and 7 December 1988, 42 patients had evidence of their first episode of cryptococcal meningitis, of whom 21 participated in the trial. All patients enrolled were men with the acquired immunodeficiency syndrome (AIDS) except one woman who was receiving prednisone therapy and was excluded from the final analysis. RESULTS: Of 14 patients with AIDS assigned to fluconazole, 8 (57%; 95% CI, 29% to 82%) failed; none of the 6 patients with AIDS failed who were assigned to amphotericin B plus flucytosine therapy (0%; CI, 0% to 46%) (Fisher exact test, P = 0.04). The mean duration of positive cerebrospinal fluid cultures was 40.6 +/- 5.4 days in patients receiving fluconazole and 15.6 +/- 6.6 days in patients receiving amphotericin B plus flucytosine (Mann-Whitney test, P = 0.02). Overall, 4 patients assigned to fluconazole therapy died whereas no patient assigned to amphotericin B plus flucytosine therapy died (Fisher exact test, P = 0.27). CONCLUSION: Amphotericin B used in combination with flucytosine has superior mycologic and clinical efficacy compared with fluconazole for the treatment of cryptococcal meningitis in patients with AIDS. PMID- 2197909 TI - Quality-of-life changes and hearing impairment. A randomized trial. AB - OBJECTIVE: To assess whether hearing aids improve the quality of life of elderly persons with hearing loss. SETTING: Primary care clinics at a Bureau of Veterans Affairs hospital. PATIENTS: One hundred and ninety-four elderly veterans who were identified as being hearing impaired from a screening survey involving 771 consecutive clinic patients. Of the original 194, 188 (97%) completed the trial. INTERVENTION: Subjects were randomly assigned to either receive a hearing aid (n = 95) or join a waiting list (n = 99). MAIN ENDPOINTS: A comprehensive battery of disease-specific and generic quality-of-life measures were administered at baseline, 6 weeks, and 4 months. MEASUREMENTS AND MAIN RESULTS: Persons assigned to the two groups were similar in age, ethnicity, education, marital status, occupation, and comorbid diseases. At baseline, 82% of subjects reported adverse effects on quality of life due to hearing impairment, and 24% were depressed. At follow-up, a significant change in score improvements for social and emotional function (34.0; 95% CI, 27.3 to 40.8; P less than 0.0001), communication function (24.2; CI, 17.2 to 31.2; P less than 0.0001), cognitive function (0.28; CI, 0.08 to 0.48; P = 0.008), and depression (0.80; CI, 0.09 to 1.51; P = 0.03) was seen in subjects who received hearing aids compared with those assigned to the waiting list. Six drop-outs (three per group), no crossovers, and no significant changes in cointerventions were seen. Average, self-reported, daily aid use in the hearing aid group was 8 hours. CONCLUSION: Hearing loss is associated with important adverse effects on the quality of life of elderly persons, effects which are reversible with hearing aids. PMID- 2197910 TI - Inhaled or intravenous pentamidine therapy for Pneumocystis carinii pneumonia in AIDS. A randomized trial. AB - OBJECTIVE: To compare inhaled pentamidine with intravenous pentamidine for the treatment of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome (AIDS). DESIGN: A randomized trial. SETTING: Community teaching hospital and hospital-based outpatient treatment center. PATIENTS: Twenty-one homosexual men with pneumocystis pneumonia; 11 received inhaled pentamidine and 10 received intravenous pentamidine. INTERVENTION: Inhaled (8 mg/kg body weight) or intravenous (4 mg/kg body weight) pentamidine administered daily for 21 days. MEASUREMENTS AND MAIN RESULTS: All patients responded to intravenous pentamidine, whereas 6 of 11 (55%; 95% CI, 23% to 83%; P = 0.02, Fisher exact test) responded to inhaled pentamidine therapy. Two patients who failed inhaled pentamidine therapy eventually died despite appropriate intravenous therapy (mortality rate, 18%; CI, -6% to 42%). Nonresponders to inhaled pentamidine had a greater severity of illness compared with responders to this therapy, as shown by a lower mean (+/ SE) Pao2 (8.0 +/- 0.4 kPa compared with 10.8 +/- 0.6 kPa; P = 0.005) and higher alveolararterial Po2 difference (6.8 +/- 0.6 kPa compared with 2.8 +/- 0.8 kPa; P = 0.003). CONCLUSIONS: Inhaled pentamidine is probably as effective as intravenous pentamidine in patients with mild pneumocystis pneumonia. However, its use as sole therapy in patients with moderate to severe pneumocystis pneumonia is not supported by the results of our study and is not warranted. PMID- 2197911 TI - Intravenous or inhaled pentamidine for treating Pneumocystis carinii pneumonia in AIDS. A randomized trial. AB - OBJECTIVE: To evaluate the efficacy and toxicity of aerosolized pentamidine and of reduced-dose intravenous pentamidine for the treatment of mild to moderate Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Randomized open study with serial pulmonary function testing and measurement of pentamidine concentrations in plasma and bronchoalveolar lavage fluid. PATIENTS: Of 44 men and 1 woman with a mild to moderate first episode of P. carinii pneumonia (Pao2 greater than or equal to 7.3 kPa [55 mm Hg]), 23 received aerosolized pentamidine and 22, intravenous pentamidine. INTERVENTIONS: Pentamidine isethionate, 600 mg by inhalation using a Respirgard II nebulizer (Marquest Medical Products, Inc., Englewood, Colorado) or 3 mg/kg body weight intravenously, administered once daily for 2 to 3 weeks. MEASUREMENTS AND MAIN RESULTS: The planned 60-patient study was stopped after 45 patients had been enrolled. The rates (aerosolized compared with intravenous pentamidine) of initial failure, early recrudescence of symptoms, and relapse were 12% and 19% (difference, 7%; 99% confidence interval [CI], - 23% to 37%; P = 0.67), 35% and 0% (difference, 35%; CI, 13% to 58%; P = 0.02), and 24% and 0% (difference, 24%; CI, 4% to 49%; P = 0.03). The rates (aerosolized compared with intravenous pentamidine) of major toxicity were 0% (0 of 17 patients) and 10% (2 of 21 patients) (difference 10%; CI, -1% to 29%; P = 0.24). The mean (+/- SD) pentamidine concentration in bronchoalveolar lavage fluid for patients receiving aerosolized pentamidine was 96.6 +/- 65.1 ng/mL compared with 14.4 +/- 17.7 ng/mL for patients receiving intravenous treatment. Trough concentrations of pentamidine in plasma increased from 0 to 25.4 +/- 16.4, 56.5 +/- 26.1, and 61.1 +/- 56.0 ng/mL at the end of weeks 1, 2, and 3 of intravenous therapy, respectively. CONCLUSIONS: The data suggest that reduced-dose intravenous pentamidine was more effective than aerosolized pentamidine for treating mild to moderate P. carinii pneumonia. Systemic absorption during aerosolized therapy was minimal; daily doses of intravenous pentamidine resulted in increased accumulation of pentamidine in plasma. PMID- 2197912 TI - Septic shock in humans. Advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy. AB - Septic shock is the commonest cause of death in intensive care units. Although sepsis usually produces a low systemic vascular resistance and elevated cardiac output, strong evidence (decreased ejection fraction and reduced response to fluid administration) suggests that the ventricular myocardium is depressed and the ventricle dilated. In survivors, these abnormalities are reversible. Failure to develop ventricular dilatation in nonsurvivors suggests that dilatation is a compensatory mechanism needed to maintain adequate cardiac output. With a canine model of septic shock that is very similar to human sepsis, myocardial depression was confirmed using load-independent measures of ventricular performance. Endotoxin administration to humans simulates the qualitative, cardiovascular abnormalities of sepsis. The pathogenesis of septic shock is extraordinarily complex. Diverse microorganisms can generate toxins, stimulating release of potent mediators that act on vasculature and myocardium. A circulating myocardial depressant substance has been closely associated with the myocardial depression of human septic shock. Therapy has emphasized early use of antibiotics, critical care monitoring, aggressive volume resuscitation, and, if shock continues, use of inotropic agents and vasopressors. Pharmacologic or immunologic antagonism of endotoxin or other mediators may prove to enhance survival in this highly lethal syndrome. PMID- 2197913 TI - Injury prevention in primary care. PMID- 2197914 TI - Medical authorship: traditions, trends, and tribulations. PMID- 2197915 TI - Mortality from Plasmodium falciparum malaria in travelers from the United States, 1959 to 1987. PMID- 2197916 TI - Feedback mechanisms and dynamics of atrioventricular node propagation. PMID- 2197918 TI - Dynamics of synchronization in the sinoatrial node. PMID- 2197917 TI - Resonance in oscillatory and excitable systems. PMID- 2197919 TI - The sinus node and atrial arrhythmias. PMID- 2197920 TI - Modeling ventricular parasystole. PMID- 2197921 TI - Vortex action potentials in normal ventricular muscle. AB - A remarkable feature of healthy ventricular myocardium, exposed by electrical stimulation and high-resolution mapping, is that, despite its gross nonuniformities and structural discontinuities on the submillimeter scale, it behaves electrically so much like a continuous uniformly anisotropic excitable medium. Such media are susceptible to a self-sustaining high-frequency periodic mode of activity in the form of freely movable paired vortices in two dimensions or vortex filaments in three dimensions. These can be evoked by a timely stimulus of the right size, for example, in myocardium by an electrical stimulus during the vulnerable period. Such stimuli may occur at random within complex patterns of stimulation and activation, even in healthy uniform tissue. Discontinuities and heterogeneity apparently make diseased tissue more vulnerable. Such vortices may underlie common reentrant tachycardias that degenerate into ventricular fibrillation, the commonest cause of sudden cardiac death. If the normal mechanism here reviewed also plays a role in diseased tissue, then it provides a quantitative basis for design of improved procedures for management of reentrant ventricular tachycardias that threaten to degrade to fibrillation. PMID- 2197922 TI - Autowave approaches to cessation of reentrant arrhythmias. PMID- 2197923 TI - Electrophysiology of spiral waves in two dimensions: the role of anisotropy. PMID- 2197924 TI - The effects of gap junctions on propagation in myocardium: a modified cable theory. PMID- 2197925 TI - Mechanisms underlying ventricular tachycardia and fibrillation in the ischemic heart: relation to nonlinear dynamics. PMID- 2197926 TI - Chaotic behavior in excitable systems. AB - This paper has dealt with biophysically accurate, or plausible, excitation systems. These are obtained from experiments, and so are complicated, often of high order, and are continually being updated by new experimental results. This is especially true for the excitation equations that represent cardiac tissue. Biophysically relevant problems require quantitatively accurate answers: What happens at what values of what parameter? Thus, numerical methods and results are important, and there is a strong tendency for both the model and the method of analysis to be given as computer algorithms; a current model for cardiac membrane dynamics is a computer package, and the use of path tracking procedures such as AUTO or PATH is becoming common. Perhaps the best way to proceed in the investigation of complicated and exotic dynamics in models of cardiac tissue would be to combine model formulation from voltage clamp data (the derivation of the excitation equations) with bifurcation, and even perhaps singularity theory analysis of dynamical systems, into an expert system. PMID- 2197928 TI - Toward very simple generic models of excitable cells. Order and chaos in cardiac tissues. Facts and conjectures. PMID- 2197927 TI - Complex bifurcations and chaos in simple theoretical models of cardiac oscillations. PMID- 2197929 TI - Searching for chaos in fibrillation. PMID- 2197930 TI - Fractal activity in cell membrane ion channels. PMID- 2197931 TI - Fractal branchings: the basis of myocardial flow heterogeneities? PMID- 2197932 TI - Fractal electrodynamics of the heartbeat. PMID- 2197933 TI - Mechanisms for nonuniform propagation along excitable cables. AB - We have discussed two classes of mechanisms that can lead to propagation with nonconstant velocity, and to disruption of temporal patterning of action potentials. Inhomogenieties along the cable due to geometrical change or to altered cell coupling can result in conduction delays, with the possibility of block or reflection. Such conduction irregularities have been considered relevant to cardiac reentry phenomena. Our simulations with a discrete number of excitable cells, coupled by gap junctions, showed that the underlying mathematical structure of a saddle point threshold in an ionic model also contributes in an important way to creating a long delay. Such threshold behavior, although not yet demonstrated for some of the most well-studied models of excitability, should not be viewed as extraordinary; we have seen it in models other than those of references 6 and 7, and have produced it in the Hodgkin-Huxley model with reasonable parameter variations (but have not yet checked for reflections with these modifications). We are unaware of any computations with theoretical models of cardiac membrane that yield robust reflection behavior. Perhaps modifications of these models will be necessary in order to obtain adequate delays for reflection. The mechanism we have described here may serve as a guideline for additional features to seek in such parametric tuning. A different class of factors that contribute to interferring with action potential timing include the effects of previous activity on propagation speed. These influences may be described in terms of the dispersion relation, c(T), the dependence of speed on time between action potentials. The form of this function, for large T, reflects the exponential behavior of the action potential's return to rest. Supernormal conduction reveals itself in the dispersion relation when there is an overshoot of excitability in the return to rest, either a single overshoot or an alternating sequence of over- and undershoots (as seen in some nerve membrane models). A simple kinematic recipe was described for quantitatively predicting timing changes during propagation without having to solve the full cable equations. To apply these concepts to cardiac models it will be necessary to compute the dispersion relation for these models. By studying the dependence of c(T) and the waveform trajectory (including conductances as well as membrane potential) on various parameters one may gain insight into the ionic basis for experimentally observed supernormal conduction. PMID- 2197934 TI - Properties of discontinuous anisotropic propagation at a microscopic level. PMID- 2197935 TI - Spiral waves in two-dimensional excitable media. PMID- 2197936 TI - Anisotropic reentry in the epicardial border zone of myocardial infarcts. PMID- 2197937 TI - The menopause in perspective. From potions to patches. AB - This article attempts to survey our current understanding of the human female climacteric and the role of hormone replacement in its treatment. As a potential endocrinopathy, the climacteric deserves appropriate diagnostic recognition and selective preventive pharmacotherapy. The impact of sometimes conflicting influences such as nutritional, dietary or lifestyle changes, exercise, smoking, drugs, alcohol and other medications, all need differentiation from true hormonal responses. The climacteric, one syndrome occurring over a period of time, has potentially lethal effects, notably coronary heart disease and complications of osteoporotic fractures. However, therapy itself carries major problems, the cancer question being the most important. The dilemma of risk-benefit planning is reviewed and likely future developments are outlined. The role of the new North American Menopause Society is explained. PMID- 2197938 TI - Methodological issues in menopause research. PMID- 2197939 TI - Follicular depletion during the menopausal transition. AB - From mid-fetal life, the human ovary steadily loses follicles. While age-related alterations at the level of the hypothalamus-pituitary appear to determine the timing of menarche, the number of follicles remaining in the mature ovary is the major determinant of the timing of both the perimenopause and the menopause. As the residual follicle reserve nears exhaustion, some of the remaining follicles appear to be defective, as evidenced by the higher incidence of chromosomal abnormalities in the ova of older women. It is presently not possible, however, to distinguish the specific contribution of the ovum to the age-related decrease in fecundity and higher abortion rate because of such confounding variables as aging sperm or changes in the endometrium. When follicle counts from peri- and postmenopausal ovaries are placed with those from previous studies of younger women and children there appears to be an acceleration in the rate of follicle loss in the decade preceding menopause. We hypothesize that the elevated FSH levels observed in normal women in the decade preceding the menopause may be responsible for this apparent acceleration in the rate of follicle loss. PMID- 2197941 TI - Menopause and adult development. PMID- 2197940 TI - Cultural and subcultural meanings of the menopause. PMID- 2197942 TI - Sociological perspectives on the medicalization of menopause. PMID- 2197943 TI - Nurse-researchers respond to the medicalization of menopause. PMID- 2197945 TI - Exercise and health maintenance in menopausal women. PMID- 2197944 TI - Menopause and heart disease. A review. AB - A large number of studies of disparate design are reasonably consistent in demonstrating that women with early bilateral oophorectomy are at increased risk of coronary heart disease. The evidence for an increase in risk among women with a surgical menopause but without bilateral oophorectomy is inconclusive, but such an effect, if any, could plausibly be explained by decreased ovarian function in many of those women as a consequence of the surgery. These findings, taken together with the lack of excess risk in women with bilateral oophorectomy who take replacement estrogen, support the view that the increased risk is due to estrogen deficiency. This view is further supported by the improvement in the lipid profile induced by estrogen replacement therapy in postmenopausal women. Because ovarian function begins to decline well before menopause, and continues to decline after menopause, it is not surprising that the moment of menopause is not associated with an abrupt increase in risk of heart disease. Moreover, some time is required for the adverse changes in coronary risk factors that occur during the climacteric to be reflected in increased rates of coronary disease. Although natural menopause does not cause an immediate increase in risk of heart disease, it does signal a period of increasing risk that is probably related both to age and to estrogen deficiency. PMID- 2197946 TI - The epidemiology of cardiovascular disease in postmenopausal women. AB - This manuscript has described the principal modifiable risk factors for the major killer of postmenopausal women. Clearly women who smoke should be convinced to quit, and those who have hypertension and hypercholesterolemia should be encouraged initially to adopt hygienic interventions (that is weight reduction and moderate exercise) to lower their blood pressures and cholesterol levels. Further, given the magnitude of the risk reduction in CVD seen in estrogen users, estrogen use ought to be considered as a preventive therapy for postmenopausal women, but particularly for those who are at high risk of cardiovascular disease. PMID- 2197947 TI - Estrogen and cardiovascular disease. PMID- 2197948 TI - Epidemiology of osteoporosis: predicting who is at risk. AB - A number of risk factors have been associated with osteoporosis, but few of them are particularly strong predictors of low bone mass or increased fracture incidence and the "best" set of variables changes from study to study. This does not provide adequate precision for classifying individual patients, and the focus of risk assessment, especially in perimenopausal women, has been on in vivo bone mass measurements. Prospective studies show that these values correspond to subsequent fracture incidence, and there is currently no alternative to bone mass measurements for stratifying patients by fracture risk. However, the level of risk at which treatment should be initiated for fracture prevention has not been agreed upon. Additional research is needed to refine risk factors for low bone mass and for falls and to design interventions to reduce the impact of osteoporosis in the population. PMID- 2197949 TI - Progress in radiology: dual-energy radiographic absorptiometry for bone densitometry. Current status and perspective. PMID- 2197950 TI - Estrogen in prevention and treatment of osteoporosis. AB - Estrogen has clearly been shown to decrease bone loss and frequency of osteoporotic fractures. Calcitonin has been shown in several studies to reduce the rate of bone loss, although no data are yet available demonstrating a reduction in fracture frequency. Studies of osteoporosis intrinsically assume that prevention of further loss, or increments in bone mass, will be associated with declines in fracture recurrence. That may not always be the case. Recent controlled studies in which fluoride was used to increase bone mass in vertebral bodies resulted in no significant decline in fracture recurrence, and there was even a suggestion of increased fracture risk at some sites. Thus further data on calcitonin will be important, even though calcitonin is not expected to alter bone quality as does fluoride. Alternative therapies to calcitonin and estrogen are being investigated in clinical studies since both are currently limited in their use. Because calcitonin currently requires nearly daily injections, estrogen remains the principal agent available for both prevention and treatment in spite of its wide effect on multiple body systems. Bisphosphonates, given continuously or intermittently, appear to be relatively safe oral alternatives to calcitonin. The long-term effects of these agents need to be evaluated in greater detail before they can be recommended for prevention, but a role in therapy of the established disorder seems likely. The skeletal effect of bisphosphonates is also inhibition of bone remodeling and therefore prevention of further bone loss. Thus, they add nothing to the other therapeutic regimens from this perspective and as with calcitonin therapy, documentation of decreased frequency of fracture is lacking. Agents to increase bone mass are purely investigational at this time and many years may elapse before efficacy can be shown for such interventions. PMID- 2197951 TI - Menopause and the risk of breast cancer. AB - In summary, although there is a fair amount of inconsistency regarding the effects of menopausal estrogen therapy on the risk of breast cancer, this may relate to inability of some studies to fully assess effects related to long-term and/or high-dosage usage, the exposures that appear to be most consistently related to elevations in breast cancer risk. Many relationships, however, remain unresolved. For example, there is only scant epidemiologic information available on the relationship of breast cancer risk to exposure to estrogens in forms other than pills, such as injectable estrogen cream, or patches. Also unclear is whether different estrogens have discrepant effects. For example, in the recent Swedish study, the primary estrogen prescribed was estradiol, a more potent estrogen than the conjugated estrogens commonly prescribed in the United States. Few studies, all based on limited numbers of exposed women, have provided data regarding effects of combined estrogen/progestin therapy, and further investigations are vitally needed to assess effects on breast cancer risk of progestins added to the commonly used estrogens in this country, including conjugated estrogens and diethylstilbestrol. Given the absence of information on the risks of breast cancer associated with menopausal estrogen therapy, especially when combined with progestins, it is extremely difficult to develop counseling approaches and for informed decisions to be made. Decisions must be made, recognizing that there are considerable benefits that have been associated with estrogen therapy, including substantial reductions in the risk of both osteoporosis and certain cardiovascular diseases. However, many relationships of risk with specific patterns of usage remain unresolved, particularly with respect to the effects on risk of combined estrogen/progestin therapy. PMID- 2197952 TI - Epidemiologic aspects of early menopause and ovarian cancer. AB - The concept of ovarian cancer as a consequence of hypergonadotropic hypogonadism implies that risk factors for early menopause may also be risk factors for ovarian cancer. Gonadal radiation and the oophoritis of mumps are possible examples of environmental risk factors for early menopause and ovarian cancer. Family history is a strong determinant for both early menopause and ovarian cancer, implicating genetic factors in these disorders. Case-control data suggest that galactose consumption through the ingestion of high-lactose dairy foods may be a dietary risk factor and that galactose metabolism, as measured by galactose 1-phosphate uridyl transferase, may be a genetic risk factor for early menopause and ovarian cancer. Supporting evidence includes animal studies, case reports, and ecologic studies. Avoidance of a high-galactose diet may decrease the risk for early menopause and ovarian cancer. Alternatively, hormonal agents that lower gonadotropins may block ovarian cancer as a consequence of oocyte toxins, even if they do not prevent the early menopause. PMID- 2197953 TI - Integrating biological and social scientific research on menopause. PMID- 2197954 TI - Hot flashes: epidemiology and physiology. AB - A review of the literature illustrates the many questions about hot flashes that remain unanswered. My survey addresses some of these questions. The prospective and retrospective descriptions of hot flashes provide a more detailed profile of the hot flash than has previously been available. Further, data from this survey demonstrate that while the patterns of hot flashes may be varied, there are commonalities in hot flash physiology and subjective manifestation. The data indicate that hot flashes may start much earlier and continue far longer than is commonly recognized by physicians or acknowledged in textbooks of gynecology. Studies of hot flash duration must control for age or age at hot flash onset, since the older the subjects, the more potential years of hot flashes and the greater the probability of encompassing the entire period of hot flashes. Hot flashes are not static; patterns may change with time. For some women, hot flashes become less frequent and less intense; for others, hot flashes may continue at hourly intervals well into old age. How common these experiences are for women of all ages still needs to be discovered. As expounded by Kaufert, McKinlay, Goodman, and many others, a greater effort must be made to standardize definitions and question formats as well as to improve methodology in epidemiologic investigations to facilitate comparability between studies and insure that proffered conclusions indeed reflect the questions being asked. Physiological studies are critical counterparts to the epidemiology; yet such studies have been too few. My work, by examining the physiology and psychophysiology of hot flashes, has raised additional questions about central and peripheral inputs that may affect the subjective experience of hot flashes. A more complete understanding of the thermoregulatory, cardiovascular, and psychophysiology of women with hot flashes are compared to women without will facilitate the prediction of who is most likely to be affected and the identification of additional approaches to the management of hot flashes. PMID- 2197955 TI - Hormonal influences on reproductive aging in mice. PMID- 2197956 TI - Sexual issues at menopause. AB - Although the desire for sexual encounters and the frequency of coitus decrease with menopause, sex in the elderly is no longer considered taboo and continues to be an important and acceptable activity for most older persons. Couples in their 50s or older expect continued sexual involvement, but most consider intercourse the only legitimate form of sexual exchange and reject other forms of sexual activity. Sexual dysfunctions which impair coital ability, especially ejaculatory difficulties in the male and genital atrophy and loss of vaginal lubrication in the female, are frequent. Menopausal couples are often not knowledgeable about physiologic aging changes that affect sexual performance and are reluctant to communicate sexual difficulties to their partner. Without professional counseling and/or pharmacologic intervention, these conditions may lead to sexual frustration and abstinence. The identification and treatment of problems, as well as patient education, are imperative in caring for the menopausal patient. PMID- 2197957 TI - Stress as a factor in lowered estrogen levels in the early postmenopause. PMID- 2197958 TI - The transforming growth factor-betas: past, present, and future. PMID- 2197959 TI - Role of transforming growth factor-beta in fracture repair. PMID- 2197960 TI - The transforming growth factor-betas. A new family of immunoregulatory molecules. AB - Within the past three years there has been a rapid expansion in our knowledge of the role TGF-beta mediates in regulating immune responses in vitro. Whether the TGF-beta will be clinically useful to suppress immune responses to transplanted organs or autoimmune responses is unknown. However, now that highly purified quantities of TGF-beta are available through recombinant DNA technologies, questions concerning the in vivo immunosuppressive activities of TGF-beta can be answered. PMID- 2197961 TI - Pharmacokinetics of TGF beta with emphasis on effects in liver and gut. PMID- 2197962 TI - Transcriptional control of expression of the TGF-betas. PMID- 2197963 TI - Analysis of proteolytic cleavage of recombinant TGF-beta 1: production of hybrid molecules with increased processing efficiency. PMID- 2197964 TI - Role of TGF beta in bone remodeling. PMID- 2197965 TI - Master lecture. Reconsidering some of the biosynthetic pathways leading to formation of C19-steroids. PMID- 2197966 TI - Experimental designs used to estimate rates of steroid production and metabolism in vivo and in vitro. PMID- 2197967 TI - Regulation of estrogen concentrations in human breast tissues. PMID- 2197968 TI - Steroid hormones and growth factors in breast cancer. PMID- 2197969 TI - Receptor-associated nuclear proteins and steroid/antisteroid action. PMID- 2197970 TI - Purification, cloning, complementary DNA structure, and predicted amino acid sequence of human estradiol 17 beta-dehydrogenase. PMID- 2197972 TI - Estradiol-fatty acid esters. Endogenous long-lived estrogens. PMID- 2197971 TI - Progestin-induced fatty acid synthetase in breast cancer. From molecular biology to clinical applications. PMID- 2197973 TI - Immunohistochemical study of cerebral amyloid angiopathy. III. Widespread Alzheimer A4 peptide in cerebral microvessel walls colocalizes with gamma trace in patients with leukoencephalopathy. AB - Brain tissue from 11 patients with cerebral amyloid angiopathy, changes of Alzheimer's disease, and variable degrees of subcortical leukoencephalopathy was examined by immunohistochemical methods, using primary antibodies to peptide segments representing portions of the Alzheimer A4 (beta-) peptide or gamma-trace peptide (seen most commonly in Icelandic patients with cerebral hemorrhage (hereditary cerebral hemorrhage with amyloidosis [HCHWA-I]). Variable A4 immunostaining was seen within cortical (and rarely white matter) parenchyma in the form of senile plaques (with or without central cores), and within capillary and arteriolar walls. Within individual patients, A4 deposits were often primarily parenchymal or vascular, and when they were vascular they tended to be more prominent in arteriolar than in capillary wall segments. Perivascular A4 deposits were often detected around strongly immunoreactive microvessels. Gamma trace immunoreactivity was noted in many A4-positive microvessel walls, but staining was always less intense than with the anti-A4 antibody. We conclude that patients with severe cerebral amyloid angiopathy may show wide variation in the severity and topography of A4 deposits within brain parenchyma. A4 may colocalize with gamma-trace peptide, suggesting that A4 and gamma-trace forms of cerebral amyloid angiopathy may not be as biochemically distinctive as has been suggested. Other proteases or protease inhibitors may contribute to the pathogenesis of cerebral amyloid angiopathy or cerebral amyloid angiopathy-related stroke syndromes. PMID- 2197974 TI - How to succeed in research without being a genius. PMID- 2197975 TI - The classification and origins of protein folding patterns. PMID- 2197976 TI - Cadherins: a molecular family important in selective cell-cell adhesion. PMID- 2197977 TI - Pyruvoyl-dependent enzymes. PMID- 2197978 TI - The mitochondrial protein import apparatus. PMID- 2197979 TI - Peptides from frog skin. PMID- 2197980 TI - Antibody-antigen complexes. PMID- 2197981 TI - T cell receptor gene diversity and selection. PMID- 2197982 TI - The bacterial phosphoenolpyruvate: glycose phosphotransferase system. PMID- 2197983 TI - Self-splicing of group I introns. PMID- 2197984 TI - Transition-state analogues in protein crystallography: probes of the structural source of enzyme catalysis. PMID- 2197985 TI - Phytochelatins. PMID- 2197986 TI - Intermediates in the folding reactions of small proteins. PMID- 2197987 TI - Regulation of vaccinia virus transcription. PMID- 2197988 TI - Biochemical aspects of obesity. PMID- 2197989 TI - RNA polymerase B (II) and general transcription factors. PMID- 2197990 TI - Sequence-directed curvature of DNA. PMID- 2197991 TI - The family of collagen genes. PMID- 2197992 TI - Recent topics in pyridoxal 5'-phosphate enzyme studies. PMID- 2197993 TI - Defense-related proteins in higher plants. PMID- 2197994 TI - DNA recognition by proteins with the helix-turn-helix motif. PMID- 2197995 TI - In situ hybridisation. AB - In situ hybridisation of mRNA in tissues or cell preparations is a powerful technique for studying gene expression. When combined with cell phenotyping with monoclonal antibodies it gives insights into the cellular basis of disease in vivo. The technique has also been used widely to identify foreign nucleic acids- for example, bacterial or viral, in host cells. The major disadvantages of this approach in the past have been that it was technically demanding, time consuming, and provided qualitative rather than quantitative results. Now, with the use of non-radioactive probes and improved imaging systems, the full potential of this form of molecular analysis is increasingly accessible and should generate rapid advances in many fields. PMID- 2197996 TI - Recombinant autoantigens. AB - Highly specific serum autoantibodies directed at cellular macromolecules are detectable in the serum of many patients with autoimmune connective tissue diseases. This phenomenon has been useful in diagnosis and in identifying disease subsets. The mechanism whereby the immune system selects these specific targets, and their relation to the events of disease pathogenesis, remains unclear. The use of monoclonal autoantibodies has increased our knowledge of the molecular associations and components of the often complex heteropolymeric antigenic particles. The advent of antigen cDNA cloning now heralds the next stage in resolution of this understanding with the complete primary structure of the component proteins. PMID- 2197997 TI - Immunoglobulin V genes expression and mRNA sequencing in rheumatoid arthritis. AB - Antibodies to exogenous antigen and to self antigen--that is, autoantibodies, are both encoded by the combining of V, D, and J genetic elements in the heavy chain, and V and J in the light chain immunoglobulins. The mechanism which generates autoantibodies does not seem to differ from that which generates the immune response to foreign antigen, and analysis of DNA from normal and autoimmune strains of mice appears similar with no appreciable defects in the immunoglobulin germline genes. Although there is restricted use of particular gene families in murine antibodies to exogenous antigen, the preferential use of particular V genes in murine autoantibodies remains controversial. Until recently, because of the obvious limitations on human experimentation, there was little information about the genetics of the human autoimmune response. Recent developments in molecular cloning techniques, however, some of which are discussed here, have shown that the germline arrangement of the human immunoglobulin variable genes differs from that found in the mouse. Furthermore, there is increasing evidence that human autoantibodies make restricted use of the V gene repertoire, and this indicates that the human autoimmune response is less polymorphic than the murine autoimmune response. PMID- 2197998 TI - The tissue metalloproteinase family and the inhibitor TIMP: a study using cDNAs and recombinant proteins. AB - Loss of connective tissue integrity occurs in many disease processes, including rheumatoid arthritis and osteoarthritis. Although there is a high incidence of these diseases in the developed world, there is no treatment that prevents the tissue damage that occurs. Several lines of evidence suggest that uncontrolled connective tissue metalloproteinase activity is responsible for the damage, and as a consequence the inhibition of these enzymes has become the target for therapeutic intervention. Several connective tissue metalloproteinases, including collagenase, stromelysin, and gelatinase, together with tissue inhibitors of metalloproteinases (TIMPs), have been described. Because of difficulties in isolating the metalloproteinases in sufficient quantity as pure separate enzymes, however, very little knowledge has accumulated about their detailed biochemistry. For similar reasons the way in which TIMPs inhibit tissue metalloproteinases is not yet fully understood. In this article it is shown how cloning metalloproteinase and TIMP cDNAs can provide information about the structure of these enzyme and inhibitor families and how the cDNAs can be used to generate recombinant cell lines from which enzymes and inhibitors can be readily purified for further studies. PMID- 2197999 TI - Cytokine production in the rheumatoid joint: implications for treatment. AB - Cytokines are protein mediators that play a part in inflammation, the immune response, cell growth, repair, and fibrosis. All of these are continuing processes in active rheumatoid arthritis (RA), and so it would be expected that many cytokines would be actively produced in RA joints. Here, the molecular strategies devised to study the possible role of cytokines in the pathogenesis of RA, are reviewed and some of the initial results described. The relative abundance of various cytokines is 'catalogued' and then attention is turned to an attempt to discover which cytokines are of major importance in the pathogenesis. Neutralising antibodies to cytokines were used for that purpose, and it was found that tumour necrosis factor alpha (TNF alpha) is one of the major signals regulating the production of interleukin-1 in the RA, but not in the osteoarthritic joint. To understand further the dynamics of the cytokine network localisation of the cytokine producing cells by immunostaining--for example, TNF alpha, is currently being established. PMID- 2198000 TI - Pathogenicity of the enterococcus in surgical infections. AB - The enterococcus has been relegated to a position of unimportance in the pathogenesis of surgical infections. However the increasing prevalence and virulence of these bacteria prompt reconsideration of this view, particularly because the surgical patient has become increasingly vulnerable to infectious morbidity due to debility, immunosuppression, and therapy with increasingly potent antibiotics. The enterococcus is a versatile opportunistic nosocomial pathogen, causing such diverse infections as wound, intra-abdominal, and urinary tract infections; catheter-associated infection; suppurative thrombophlebitis; endocarditis; and pneumonia. Although surgical drainage remains the cornerstone of therapy for enterococcal infections involving a discrete focus, in the circumstances typified by the compromised surgical patient, specific antibacterial therapy directed against the enterococcus is warranted. Recent evidence indicates that parenteral antibiotic therapy for enterococcal bacteremia is mandatory and that appropriate therapy clearly reduces the number of deaths. PMID- 2198003 TI - Cystic lymphoepithelial lesion of the pancreas. AB - A rare lymphoepithelial lesion of the pancreas was discovered incidentally at autopsy. This lesion is composed of epithelial-lined cystic spaces encompassed by lymphoid stroma, similar to lesions reported in the salivary glands. Review of the literature revealed only three similar cases. This lesion should be considered in the differential diagnosis of pancreatic cysts. PMID- 2198001 TI - Survival following locoregional recurrence after breast conservation therapy for cancer. AB - We postulated that locoregional recurrence after limited surgery and radiotherapy for breast cancer might be associated with an additional survival hazard, similar to that of a second primary tumor with the same extent of local and regional disease. Using this hypothesis we examined the likely resultant effect on survival. Our calculations indicated that no statistically significant survival deficit due to such recurrence would be detectable until a randomized controlled trial comparing breast conservation with mastectomy had monitored more than 10,000 patients for more than 10 years. A simple mathematical model predicted 5 year survival rates in a cohort of patients treated with breast conservation of 75%, compared to 83% in those without locoregional recurrence. From the date of locoregional recurrence, a 61% 5-year survival rate was predicted, compared to 83% if no hazard was associated with locoregional recurrence. These predictions were compared with the actuarial survival rates of 499 patients with unilateral breast cancer, 49 of whom had developed locoregional recurrence. From the date of initial treatment, the 5-year survival rate of those whose disease recurred was 79%, compared to 88% for those without locoregional recurrence (p = 0.19). The actuarial 5-year survival rate from the date of locoregional recurrence was 63%. The similarity between the patient data and the predictions of the mathematical model indicates that locoregional failure after breast conservation therapy may result in reduced survival. The lack of a significant survival deficit in our cohort or in controlled trials comparing breast conservation therapy with mastectomy is compatible to the small size of the overall effect. PMID- 2198002 TI - Effects of age and body composition on the metabolic responses to elective colon resection. AB - Advancing age tends to be accompanied by predictable changes in organ-system function and body composition, as well as an increased prevalence of various diseases. Our knowledge of the metabolic responses to surgical stress is derived largely from studies of young and middle-aged individuals. Whether these responses are altered in the elderly is not well established; the characteristic changes in metabolic function and body composition that occur in the elderly may limit their ability to respond adequately and to survive severe or complicated surgical procedures. To evaluate the effects of age and differences in body composition on the metabolic responses to surgery, we studied 20 active and otherwise healthy men aged 43 to 77 years, before and after elective colon resection. Age was not related to weight or total body water (TBW) in the patients studied. Resting preoperative energy expenditure was strongly dependent on TBW (reflecting lean body mass) and age (r2 = 0.80, p less than 0.001), and to TBW and creatinine excretion (reflecting muscle mass) (r2 = 0.85, p less than 0.001). Energy expenditure increased 18 +/- 2% (range, 4% to 40%) after operation but this response was unrelated to age. Postoperative urine nitrogen was related to body weight or TBW, but not to age. Serum glucose, cortisol, white blood cell count count, and C-reactive protein responses were also independent of patient age. The metabolic responses of generally healthy men to a moderate surgical stress do not vary with age in the range studied. The metabolic responses to more severe or prolonged stress may be altered with advancing age and changes in body composition, and in patients with concomitant diseases. PMID- 2198005 TI - Non-Hodgkin's lymphoma of the adrenal gland. AB - Primary non-Hodgkin's lymphoma of the adrenal gland was diagnosed in a 64-year old woman. The histologic and immunohistologic features are characteristic of a large-cell noncleaved lymphoma (B-cell origin). The patient died 3 weeks after right-sided adrenalectomy. The patient's family refused an autopsy. PMID- 2198004 TI - Hemolytic transfusion reaction due to interdonor kell incompatibility. Report of two cases and review of the literature. AB - A 74-year-old man experienced an acute hemolytic reaction following transfusion of 4 units of red blood cells. The recipient was K negative, one of the transfused units was K positive, and another contained a previously undetected anti-K with an indirect antiglobulin titer of 512. Further investigation led to the discovery of a hemolytic transfusion reaction in a second K-negative patient who received a platelet transfusion containing 50 mL of plasma from the same donor. The clinical and serologic features of these two cases and five previously reported cases of hemolytic transfusion reaction due to interdonor Kell incompatibility are summarized. PMID- 2198006 TI - Paraganglioma of the spermatic cord. Report of a case with immunohistochemical and ultrastructural studies. AB - We describe a case of paraganglioma arising in the spermatic cord, which is an extremely rare location. Immunohistochemical studies characterized two types of cells: (1) polygonal cells expressing neuron-specific enolase, chromogranin A, and synaptophysin and (2) S100 protein-positive sustentacular cells. Electron microscopy revealed that within the cytoplasm of the polygonal cells, there were electron-dense granules whose morphological appearance was consistent with that of neurosecretory granules. Paraganglioma of the spermatic cord may originate from embryonic chromaffin cells that have followed the testis into the scrotum. PMID- 2198007 TI - Pigmented choroid plexus papilloma. AB - A pigmented choroid plexus papilloma was found in the left lateral ventricle of a 15-year-old white boy with a 10-year history of seizures. Grossly the lesion appeared finely lobular, orangish brown, rubbery, gritty, and friable. Microscopic examination revealed delicate papillary formations reminiscent of normal choroid plexus, with simple cuboidal to columnar epithelium overlying fibrovascular cores. Light- and electron-microscopic studies demonstrated that the neoplastic cell pigment consisted of both neuromelanin and lipofuscin. To our knowledge, this is the first reported case of neuromelanin pigmentation within a choroid plexus papilloma. PMID- 2198008 TI - Design of a measurement system for electrophysiological cardiac surgery. AB - The treatment of cardiac arrhythmias by surgical removal of abnormal electrical pathways across the atrio-ventricular ring or re-entrant circuits within the myocardium is dependent on the ability to accurately locate the abnormality by measuring and displaying the activation front of muscle depolarisation as it spreads across the surface of the heart. The localisation of the aberration requires induction of the arrhythmia, simultaneous measurement of activity from many (100-200) sites over the surface of the heart, attachment of fiducial markers to this data, and display of the activation sequence in the form of an isochronous map. An instrument has been built at Green Lane Hospital to provide the necessary measurement, control, and analysis facilities required by this procedure. The purpose built measurement system is a multiprocessor unit which incorporates up to 512 programmable intracardiac amplifiers, two multifunction cardiac pacing stimulators, a versatile real time data display, a patient safety isolation system, and digital storage for eight seconds of electrocardiographic data. Signals are acquired from a mesh of bipolar electrodes attached to either a 'sock' or a 'band' which is placed on the heart during open heart surgery. The analysis of data is carried out on a personal computer, connected to the measurement system via a serial command link and a high speed parallel data link. Corrective surgery is now being carried out on a routine basis for some types of arrhythmias. PMID- 2198009 TI - Stimulation with electrosurgical current. PMID- 2198010 TI - Eradication of bovine tuberculosis from New South Wales--a century of endeavour. PMID- 2198011 TI - The use of sutures in Australian veterinary practices. AB - One hundred and twenty six respondents at a continuing education course in February 1986 provided information on suture use in their practice. The 100 responses from four Australian states were subject to analysis of suture type and size used for various procedures and correlated with practice type, location and state. The use of gut and nonabsorbable sutures in cassettes was pervasive. Superior materials and sutures in individual foil packets were used commonly only for a more complicated procedure (enterotomy). PMID- 2198012 TI - Concern over publicity for ultrasound pregnancy testing of cows. PMID- 2198013 TI - The timer. AB - This article reviews the evidence that living systems at all levels, including cells, organs, organisms, groups, organizations, communities, societies, and supranational systems, have an information-processing system, the timer. The timer consists of one or more oscillators known as clocks or pacemakers, the phase of which can be reset. They measure duration or order in time or underlie rhythms of various sorts. The timer subsystem synchronizes internal processes of the system and coordinates the system with its environment. By 1965, 19 matter energy and information processing subsystems were identified in living systems theory. Based on scientific evidence accumulated particularly in recent years, the timer is now recognized as an information processing subsystem, the 20th subsystem, which carries out an essential life process. PMID- 2198014 TI - Etiological models of child maltreatment. A behavioral perspective. AB - Child abuse and neglect are complex phenomena that require a multidisciplinary perspective. This article describes current etiological formulations of child maltreatment. Three models (ecological, transactional, and transitional) are described that delineate the multiple pathways leading to abuse and neglect. These approaches emphasize the interaction of causative factors in bringing about maltreatment and the importance of high- and low-risk characteristics that differentially influence the development of maltreatment. Behavioral explanations of child maltreatment are also discussed. Particularly relevant here are observational learning, anger control, and coercive family processes. Finally, the implications of our understanding of etiology to assessment, treatment, and prevention are outlined and considered. PMID- 2198015 TI - Behavioral assessment of child-abusive and neglectful families. Recent developments and current issues. AB - Recent developments and current issues in the behavioral assessment of child abusive and neglectful families are described. Procedures for the assessment of target behaviors in a variety of areas that may be related to the occurrence of further maltreatment and improved family functioning are reviewed. The primary emphasis is on measures recently developed for maltreating populations, although some measures discussed were developed for nonmaltreating populations. A variety of issues that commonly arise in the assessment of maltreating families and future directions for practice and research are also addressed. PMID- 2198016 TI - Behavioral treatment of child abuse. A developmental perspective. AB - This article reviews cognitive and behavioral treatment strategies that have been employed with parents who physically abuse their children. Using a developmental framework, a broadened view of abuse is presented that emphasizes targets for intervention that not only reduce aversive parental behavior but also increase behaviors that lead to more optimal child outcome. Interventions with maltreaters are then described, focusing on three periods of childhood--infancy, middle childhood, and adolescence. An argument is made for there being different goal parental behaviors during each of these periods, as well as unique child-based demands that act as obstacles to parents' successfully meeting these goals. Where behavioral treatments with abusive parents do not yet exist, treatments with similar parent populations are described. The article concludes with a discussion of the treatment issues facing the field in the future. PMID- 2198017 TI - Behavioral treatment of child neglect. AB - Child neglect is a serious and prevalent problem. It is often chronic, and parents accused of child neglect may refuse treatment or may fail to cooperate fully. Described here are some examples of empirically evaluated treatments for child neglect dealing with hygiene, nutrition, home safety, and cleanliness, affective skills training, infant stimulation, and teaching health-related skills. Also discussed is a concern for a need for primary prevention programs. PMID- 2198018 TI - Behavioral treatment of the victims of child abuse and neglect. AB - Although there is a little debate that victims of child abuse and neglect suffer ill effect, scientifically validated, behavioral treatment of child victims is virtually nonexistent. This article examines three pertinent facets of the child maltreatment knowledge base: (a) national child abuse and neglect reporting, (b) empirical investigations of the psychological effects of maltreatment, and (c) a small number of treatment outcome studies. Based on this review, guidelines are presented to promote the development of practical, treatment outcome investigations that adequately reflect existing data about child victims and their life circumstances and that are responsive to their specific needs and available resources. PMID- 2198019 TI - [Intervertebral disk endoprosthesis--development and current status]. AB - The clinical use of SB endoprosthesis and new international models and research results have increased the importance of functional intervertebral disc prosthetics as an alternative method to certain fusion operations. An analysis of the development of intervertebral disc prostheses and special problems regarding this development will be discussed. PMID- 2198021 TI - Regulation of lipoprotein lipase activity and mRNA content in rat epididymal adipose tissue in vitro by recombinant tumour necrosis factor. AB - Tumour necrosis factor (TNF) has previously been shown to decrease lipoprotein lipase (LPL) activity and mRNA levels in 3T3-L1 cells and in adipose tissue from rats and guinea pigs when injected in vivo, but not to alter LPL activity in human adipocytes incubated in vitro. The effect of recombinant human TNF on LPL activity and mRNA levels in rat epididymal adipose tissue incubated in vitro was examined. LPL activity and mRNA levels fell in adipose tissue taken from fed rats and incubated in Krebs-Henseleit bicarbonate medium with glucose. The addition of insulin and dexamethasone prevented these falls. TNF (400 ng/ml) produced a fall of approx. 50% in LPL activity after 2 h of incubation and of approx. 30% in LPL mRNA levels after 3 h. TNF did not decrease LPL activity in isolated adipocytes. These results demonstrate that rat adipose tissue incubated in vitro is responsive to TNF whereas isolated adipocytes are not. PMID- 2198020 TI - The glyoxalase system: new developments towards functional characterization of a metabolic pathway fundamental to biological life. PMID- 2198022 TI - Purification and characterization of cytosolic aldolase from carrot storage root. AB - A single fructose-1,6-bisphosphate (FBP) aldolase has been detected in extracts from carrot storage roots (Daucus carota L.). The enzyme was purified 850-fold to electrophoretic homogeneity and a final specific activity of 26.3 mumols of FBP utilized/min per mg of protein. SDS/PAGE of the final preparation revealed a single protein-staining band of 40 kDa. The native molecular mass was determined by analytical gel filtration to be 159 kDa, indicating that the enzyme is a homotetramer. Denaturing isoelectric focusing revealed two predominant protein staining bands, with pI values of 5.6 and 5.7. The enzyme is a class I aldolase, since EDTA or metal ions had no effect on its activity. The enzyme was relatively heat-stable, had an activation energy (Ea) of 68.3 kJ.mol-1, and had an absorption coefficient of 8.08 x 10(4) M-1.cm-1 at 280 nm. Km values for FBP and sedoheptulose 1,7-bisphosphate (SBP) were both determined to be 6 microM (pH optima 7.4). The specificity constant with FBP was 2.6 times that obtained with SBP. Ribose 5-phosphate, 6-phosphogluconate, MgAMP, glucose 1-phosphate and phosphoenolpyruvate (PEP) were inhibitors. PEP was a mixed-type inhibitor with respect to FBP (Ki = 3.2 mM, K'i = 5.1 mM). No activators were found. Rabbit anti (carrot aldolase) polyclonal antibodies immunoprecipitated the activity of both carrot root aldolase and spinach leaf cytosolic aldolase, but not that of spinach leaf plastid aldolase. Western-blot analysis also revealed cross-reactivity with cytosolic, but not plastid, spinach leaf aldolase, indicating that the single carrot root aldolase is cytosolic. PMID- 2198023 TI - The effects of amylin on carbohydrate metabolism in skeletal muscle in vitro and in vivo. AB - 1. The effects of synthetic human amylin on basal and insulin-stimulated (100 and 1000 microunits/ml) rates of lactate formation, glucose oxidation and glycogen synthesis were measured in the isolated rat soleus muscle preparation incubated in the presence of various concentrations of glucose (5, 11 and 22 mM). 2. The rate of glucose utilization was increased by about 2-fold by increasing the glucose concentration from 5 to 22 mM. 3. Synthetic human amylin (10 nM) significantly inhibited (by 46-56%) glycogen synthesis, irrespective of the concentration of insulin or glucose present in the incubation medium. 4. Amylin (10 nM) did not affect insulin-stimulated rates of 2-deoxy[3H]glucose transport and phosphorylation. 5. Intraperitoneal administration of insulin (100 micrograms/kg) to rats in vivo stimulated the rate of [U-14C]glucose incorporation into glycogen in the diaphragm by about 80-fold. This rate was decreased (by 28%) by co-administration of amylin (66 micrograms/kg). PMID- 2198024 TI - Revised interpretation of the sequence containing the murE gene encoding the UDP N-acetylmuramyl-tripeptide synthetase of Escherichia coli. PMID- 2198025 TI - Intermediate filaments in smooth muscle from pregnant and non-pregnant human uterus. AB - The intermediate filament proteins desmin and vimentin from pregnant and non pregnant uterine muscle and smooth-muscle cells in culture were analysed using SDS/PAGE. The desmin content in uterine muscle increases dramatically during pregnancy, whereas vimentin remains unchanged or changes very little. When muscle cells are kept in culture, a considerable increase in vimentin content is observed as compared with vimentin in freshly isolated non-pregnant uterine tissue. Our results strengthen the view that vimentin and desmin filaments have independent function and turnover, and point to a predominantly structural role for desmin filaments. PMID- 2198026 TI - Comparative study on glucocerebrosidase in spleens from patients with Gaucher disease. AB - In Gaucher disease (glucosylceramide lipidosis), deficiency of glucocerebrosidase causes pathological storage of glucosylceramide, particularly in the spleen. A comparative biochemical and immunological analysis has therefore been made of glucocerebrosidase in spleens from normal subjects (n = 4) and from Gaucher disease patients with non-neuronopathic (n = 5) and neuronopathic (n = 5) phenotypes. The spleens from all Gaucher disease patients showed markedly decreased glucocerebrosidase activity. Discrimination of different phenotypes of Gaucher disease was not possible on the basis of the level of residual enzyme activity, or by measurements, using the immunopurified enzyme, of kinetic constants, pI or molecular mass forms. A severe decrease was found in the specific activity of glucocerebrosidase purified to homogeneity from the spleen of a patient with the non-neuronopathic phenotype of Gaucher disease, as compared with that of the enzyme purified from the spleen of a normal subject. This finding was confirmed by an immunological method developed for accurate assessment of the relative enzyme activity per molecule of glucocerebrosidase protein. The method revealed that the residual enzyme in the spleens of all investigated patients with a non-neuronopathic course of Gaucher disease had a more than 7-fold decreased activity of glucocerebrosidase (measured in the presence of taurocholate) per molecule of enzyme, and that the concentration of glucocerebrosidase molecules in the spleens of these patients was near normal. Observations made with immunoblotting experiments were consistent with these findings. In contrast, in the spleens of patients with neuronopathic phenotypes of Gaucher disease, the concentration of glucocerebrosidase molecules was severely decreased. PMID- 2198027 TI - Comparison of the in vitro activities of quassinoids with activity against Plasmodium falciparum, anisomycin and some other inhibitors of eukaryotic protein synthesis. AB - Using the inhibition of incorporation of [3H]hypoxanthine as an index of viability of malaria parasites, it was shown that a chloroquine-sensitive strain of Plasmodium falciparum (T9-96) and a chloroquine-resistant strain (K1) did not differ in their sensitivities to the quassinoids ailanthinone, bruceantin and chaparrin. Similarly, there were no differences between the strains in their sensitivities to the protein synthesis inhibitors anisomycin, deacetylanisomycin, cephalotaxine, homoharringtonine, cycloheximide, puromycin and puromycin aminonucleoside. The IC50 values derived for ailanthinone and bruceantin, cycloheximide, homoharringtonine and puromycin were in the nanomolar range, whereas those for the anisomycins, cephalotaxine and the aminonucleoside of puromycin were micromolar or greater. Those drugs tested which contain an ester moiety (ailanthinone, bruceantin, anisomycin, homoharringtonine) were more active than the related drugs (chaparrin, deacetylanisomycin, cephalotaxine) that do not. Cross-resistance to inhibitors of protein synthesis appeared not to accompany resistance to chloroquine. PMID- 2198028 TI - [Crystal structure of thermitase and stability of subtilisins]. AB - Crystal structure of thermitase, a serine proteinase from Thermoactinomyces vulgaris, has been determined by X-ray diffraction at 1.4 A resolution. The atomic model of thermitase refined to an R-factor of 0.149 contains 1997 protein atoms, 182 water molecules and 2 Ca2+ ions. The tertiary structure of thermitase is similar to that of subtilisin BPN'. The greatest variations are connected with insertions and deletions in the amino acid sequence, which are located on the surface of the molecule. Higher thermostability of thermitase can be explained in terms of the three-dimensional structure. The Ca2+ ions, bound to the protein molecule, as well as the ionic and hydrophobic interactions are supposed to give the main contribution to the stabilization of the structure. PMID- 2198029 TI - Visualization of apo B, fibrinogen/fibrin, and fibronectin in the intima of normal human aorta and large arteries and during atherosclerosis. AB - Apolipoprotein B (apo B), fibrinogen/fibrin, blood platelets, factor VIII-related antigen of the blood coagulation system, and smooth muscle cells (SMC) were identified in the intima of normal and atherosclerotic human aorta and large arteries by the indirect immunofluorescence technique. Fibrinogen/fibrin was revealed by a monoclonal antibody (monAb) against the C-terminal region of human fibrinogen A alpha-chain. Fibronectin was visualized by monAb to the cellular form and against an epitope shared by different fibronectin subunit variants. In normal intima, fatty streaks, small amounts of fibrinogen/fibrin together with large amounts of apo B were observed. Fibronectin detected by two types of monAb was not found in extracellular matrix (ECM), whereas cellular fibronectin encircled SMC. According to the data obtained, fibrinogen/fibrin accumulates in plaques as a result of intramural thrombus incorporation, blood insudation, intramural haemorrhage, and in or around cells, apparently macrophages. PMID- 2198031 TI - Alcohol and membrane-associated signal transduction. AB - In recent years, ethanol has been shown to interact with membrane-associated signal transduction mechanisms which rely on the reaction of phospholipases with their phospholipid substrates in the membrane. In several cell and membrane preparations, ethanol activates the polyphosphoinositide-specific phospholipase C and triggers the complete battery of intracellular signalling responses that are characteristic for hormones acting through this pathway, including the formation of inositol-1,4,5-trisphosphate, the release of Ca2+ from intracellular storage sites with the consequent activation of cytosolic Ca2(+)-dependent enzymes, and the formation of diacylglycerol leading to the stimulation of protein kinase C. The activation of phospholipase C appears to be due to an interaction of ethanol with the intramembrane complex of receptor-G-protein-phospholipase C, presumably promoting the release of bound GDP and the binding of GTP to activate the G protein which controls phospholipase C activity. In many intact cells, the phospholipase C is subject to a feedback inhibitory control by protein kinase C. In liver cells, ethanol also triggers this feedback inhibition, leading to a rapid decline in the phospholipase C activation; at the same time, ethanol also causes the desensitization of the response to vasopressin and other phospholipase C-linked agonists. At hormone concentrations in the physiological range, the heterologous desensitization by ethanol of the agonist-mediated phospholipase C activation may be a significant factor at ethanol concentrations that are readily attained in vivo. Further interaction of ethanol with the intracellular second messenger system is mediated through a hormone-sensitive phospholipase D. This enzyme uses phosphatidylcholine to generate phosphatidic acid which can be further converted to diacylglycerol. In the presence of ethanol the enzyme catalyzes the transphosphatidylation to phosphatidylethanol. It is not clear, however, under what conditions this process could affect the normal pattern of formation of second messenger molecules. After chronic ethanol intake, a tolerance can develop at the cellular level to the effects of ethanol on agonist induced signal transduction processes. However, the mechanism by which this tolerance develops is currently a matter of conjecture. Studies on liver cells indicate that the activity of protein kinase C may play a role in the development of this type of tolerance to ethanol. A better understanding of the interaction of ethanol with these phospholipid-dependent signal transduction processes could point to mechanisms by which ethanol could interfere with physiological control mechanism in a variety of cells and tissues. PMID- 2198030 TI - Alcohol and aldehyde dehydrogenase. AB - The enzymes mainly responsible for ethanol degradation in humans are liver alcohol dehydrogenases (ADH) and aldehyde dehydrogenases (ALDH). Polymorphisms occur in both enzymes, with marked differences in the steady-state kinetic constants. The Km-values for ethanol of ADH isoenzymes relevant for alcohol degradation range from 49 microM to 36 microM, and the Vmax-values from 0.6 to 10 U/mg. Expression of an inactive form of the ALDH2 isoenzyme, the so-called Oriental variant, results in impaired acetaldehyde metabolizing capacity. The differences in ethanol and acetaldehyde metabolizing activities of allelic enzyme forms may be responsible in part for the large variation in the alcohol metabolism rate in humans. Interindividual differences in the isoenzyme pattern may contribute to the genetically determined predisposition for excessive alcohol intake. PMID- 2198032 TI - Interaction of ethanol with drugs, hepatotoxic agents, carcinogens and vitamins. AB - Ethanol has been shown to have a multitude of acute and chronic interactions with xenobiotic agents, many of which can now be explained on the basis of the existence of a newly recognized microsomal ethanol oxidizing system (MEOS) involving a specific cytochrome P-450 (P450IIE1). Although such a system was proposed already two decades ago, its role was viewed with skepticism: until recently, it was commonly believed that the primary pathway for hepatic ethanol metabolism is due almost exclusively to the activity of cytosolic alcohol dehydrogenase, with a minor contribution from peroxisomal catalase. It is now recognized, however, that liver microsomes (through MEOS) participate in ethanol metabolism. The existence of this system and its inducibility contribute to the metabolic tolerance to ethanol in the alcoholic. Cross induction of other microsomal enzymes also explains the tolerance to many commonly used drugs. Most importantly, the alcohol-inducible form (P450IIE1) has a unique capacity to activate xenobiotic agents to toxic metabolites, thereby explaining the unusual susceptibility of the alcoholic to the adverse effects of other drugs, hepatotoxic agents, carcinogens and even vitamins. PMID- 2198033 TI - Alcohol and skeletal muscle disease. AB - Skeletal muscle myopathy is caused by prolonged ethanol misuse and affects between half and two-thirds of chronic alcohol misusers. This chronic myopathy is characterized by a selective reduction in Type II (fast twitch) fibre area; Type I (slow twitch) fibres are relatively unaffected. The myopathy is not mediated by the patients' corticosteroid and nutritional status, liver dysfunction or neurological changes, and there is little correlation between alcoholic myopathy and alcohol intake. However, plasma alpha-tocopherol and selenium levels in myopathic alcoholics are reduced. The myopathy may in some way be related to the reduced fractional rates of skeletal muscle protein synthesis that occur in alcohol misusers and implicates free radical reactions in the pathogenesis of the myopathy. We have established a rat model of chronic alcoholic myopathy. In this model anatomically distinct skeletal muscles were taken to represent Type I (i.e. soleus) or Type II (i.e. plantaris) fibres. There were selective losses of Type II muscle protein at the end of 6 weeks of ethanol feeding. These changes were also not apparently mediated by nutritional limitations, neurological changes or liver dysfunction. Skeletal muscle protein synthesis was also reduced, as was plasma alpha tocopherol and selenium levels. Thus the rat model is amendable for further work to elucidate the molecular mechanisms responsible for alcohol induced muscle loss. PMID- 2198034 TI - Alcoholic hepatitis. AB - Alcoholic hepatitis is a serious consequence of alcohol misuse and the usual precursor of cirrhosis. Risk factors, histology, pathogenesis, clinical features, prognosis and treatment are discussed in this review. PMID- 2198035 TI - Treatment of advanced alcoholic liver disease. AB - The poor prognosis of severe acute alcoholic hepatitis has stimulated interest in specific forms of treatment aimed at reducing the short term mortality as well as preventing progression to cirrhosis. Several controlled trials of steroid therapy have suggested an improvement in short-term survival, but the benefit seems to apply to highly selected cases only. Treatment with propylthiouracil and insulin and glucagon infusions has also shown promising results in controlled studies but there is still no general agreement on their value. Despite recent interest in the use of colchicine to prevent progression of cirrhosis in chronic liver disease of other aetiologies, its role in alcoholic liver disease is not yet clear. In end-stage alcoholic cirrhosis, excellent results are now being achieved with liver transplantation, although this is limited to patients who are not alcohol dependent and in whom there is no alcohol-induced extrahepatic disease. PMID- 2198036 TI - Neuropathology of alcoholism. AB - There are wide ranging effects of alcohol on the nervous system. Some interfere with physiological and neurochemical functions but ultimately structural damage occurs. During life one of the most impressive changes is brain shrinkage which can be visualized using neuroradiological imaging techniques. This article reviews the pathological explanations for brain shrinkage and addresses the question of the pathogenesis of the reversible component of this damage in relation to prolonged abstinence from alcohol. This shrinkage seems to relate to a loss of white matter. However, the cortex is also abnormal in that there is a loss of neurones from the frontal region. In this and other regions of the cortex examined there is shrinkage of the neuronal soma. This is reflected in a retraction of the neuronal dendritic arbor which plays a crucial role in cell-to cell communication. In addition, the cerebellum appears to be vulnerable in alcoholic patients although it may well be that associated nutritional deficiencies play an important role. The Wernicke-Korsakoff syndrome is another important deficiency disorder which is seen most frequently in alcoholic patients. Two important population groups which are considered in this review are females and moderate ('social') drinkers. Females are thought to be more susceptible to the damaging effects of alcohol than males and this is examined in the light of the scant data available. Similarly, there are few neuropathological data on people who drink 30-80 grams of alcohol per day. In order to assess so called 'safe levels of drinking' this is an important group to study. PMID- 2198037 TI - The genesis of alcoholic brain tissue injury. AB - 1. Acetaldehyde has been implicated in the pathogenesis of alcohol-related liver damage by two mechanisms. Adduct formation with many tissue constituents, especially proteins, makes them immunologically foreign or reduces enzyme activity and formation of cytotoxic free radicals from acetaldehyde metabolism. Adduct formation damage to microtubule associated proteins and to hepatocyte membranes impedes protein movement into, out of and around the cell. 2. Evidence that these mechanisms also have a role in alcoholic brain damage includes raised blood acetaldehyde in alcoholics, especially in those chemically dependent, or in other abnormal states; effects of extra-hepatic free radical toxicity, including induction of superoxide dismutase activity and damaged, abnormal variants of the thiamin-dependent enzyme transketolase and extrahepatic acetaldehyde-adduct formation with haemoglobin. That acetaldehyde-mediated impairment of microtubule systems also damages the brain is suggested by its importance for the maintenance by protein transport of often greatly extended brain cell processes. 3. Oxygen derived free radicals can damage brain tissue, the effects including cerebral oedema, neuronal loss and damage to the blood-brain barrier, all changes also reported in the brains from alcoholic patients. Alcohol-related pathology in the brain differing from that in the liver, shows sharper regional variations in vulnerability and adverse effects due to nutritional deficiencies, especially of B-group vitamins. Even though some such deficits are capable of causing encephalopathy in the non-alcoholic, the strong association between them and chronic alcoholism points to possible aggravation by metabolic interactions at various levels between acetaldehyde and thiamin or other B-vitamins. Selective regional vulnerability may reflect differences in ease of acetaldehyde access or to important metabolic differences. Alteration of animal behaviour by acetaldehyde points to a need to correlate clinical evidence of acetaldehyde central nervous cytotoxicity with the incidence of different types of cognitive defect. PMID- 2198038 TI - Ethanol-induced lipid peroxidation and oxidative stress in extrahepatic tissues. AB - An ethanol-induced oxidative stress is not restricted to the liver, where ethanol is actively oxidized, but can affect various extrahepatic tissues as shown by experimental data obtained in the rat during acute or chronic ethanol intoxication. Most of these data concern the central nervous system, the heart and the testes. An acute ethanol load has been reported to enhance lipid peroxidation in the cerebellum. This is accompanied by an increase in the cytosolic concentration of low-molecular-weight iron derivatives which may contribute to the generation of aggressive free radicals. The ethanol-induced decrease in the main antioxidant systems (superoxide dismutase, alpha-tocopherol, ascorbate and selenium) is a likely contributor to the cerebellar oxidative stress. Most of these disturbances can be prevented by allopurinol administration. Some experimental data support also the occurrence of pro- and anti-oxidant disturbances in the cerebellum and in other regions of the central nervous system after chronic ethanol administration. Chronic ethanol administration enhances lipid peroxidation in the heart. The increased conversion of xanthine dehydrogenase into xanthine oxidase as well as the activation of peroxisomal acyl CoA-oxidase linked to ethanol administration could contribute to the oxidative stress. Chronic ethanol administration elicits in the testes an enhancement in mitochondrial lipid peroxidation and a decrease in the glutathione level, which appear to be correlated to the gross testicular atrophy observed. Vitamin A supplementation attenuates the changes in lipid peroxidation, glutathione and testicular morphology. Whether the reported disturbances are involved in the pathogenesis of the tissue disorders observed in alcoholic patients remains unanswered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198039 TI - Neuroelectric processes in individuals at risk for alcoholism. AB - The literature dealing with electrophysiologic research in alcoholics and individuals at risk for alcoholism is reviewed. Event-related potential (ERP) differences between family history positive (FHP) and family history negative (FHN) males have been reported both prior to the ingestion of alcohol and following alcohol challenge doses. At present, the most robust of these electrophysiological findings is the lower P3 amplitude of the ERP, which has now been replicated in several laboratories. This perhaps provides a phenotypic marker, distinguishing those at risk for alcoholism. PMID- 2198040 TI - The alcohol problem in universities and the professions. AB - Over the past few decades the belief has grown that the drinking habits of medical students and doctors are abnormal. The literature on the subject is, however, equivocal. Some studies suggest that medical drinking is not particularly excessive. Others indicate that it is when compared with the general population but not when compared with the drinking rates and patterns of comparable professional groups. Medical student drinking is often analysed without reference to that of other young adult groups and university students. However, the growing concern about medical drinking has stimulated a number of 'impaired physician' treatment programmes designed, implemented and monitored by the profession itself. Preliminary results suggest that such programmes achieve impressive therapeutic results and contain useful indicators relating to therapeutic efficacy which may well have wider application. PMID- 2198041 TI - What's the harm in just a drink? AB - A major characteristic of prenatal alcohol intake is a subsequent birth weight decrement. Experimental animal work has demonstrated that nutritional effects apart, there is a strong, direct alcohol effect responsible for this decrement. Consistency in this effect of birth weight decrement has been demonstrated in a range of species. Early work with animals had equally demonstrated that this effect can be transitory and that catch up is possible. Quite recently, human studies have supported such animal findings to the extent that now we need to question even more strongly our approach required for counselling on alcohol consumption during pregnancy. PMID- 2198042 TI - Alcohol, sex and AIDS. AB - The association between alcohol consumption and AIDS risks is examined. It is concluded that chronic heavy drinking or alcohol consumption levels consistent with alcohol dependence or alcohol-related liver disease does damage the immune system. In addition alcohol consumption influences sexual behaviour for a variety of psychological, social and physical reasons. Attention is focused on the disinhibiting effects of alcohol and the popular belief that drinking may be used to facilitate or excuse otherwise unacceptable behaviour. Several studies indicate that alcohol consumption is associated with 'high risk' sexual behaviour. Accordingly drinking appears to be a risk factor for potential exposure to HIV infection and for relapse into 'high risk' sexual activities. Evidence does not support the conclusion that alcohol is a cofactor in the course of AIDS-related illnesses. PMID- 2198043 TI - One hundred years of excellence in nursing. The University of Cincinnati College of Nursing and Health, 1889-1989. AB - The history of the College of Nursing and Health mirrors the history of the profession. In 1889, students were handmaidens to the doctor; now they are educated to be professionals functioning within the framework of the nursing process. The College of Nursing and Health at the University of Cincinnati has flourished. It began in 1889 as a small private hospital school with five students. There are now 855 students, 54 full-time faculty and 17 part-time faculty. A doctoral program in nursing at the College of Nursing and Health, approved by the National League of Nursing, began in 1989. The College of Nursing and Health has a long history of including occupational health content in its programs, dating back to 1914. The master's program to prepare occupational health nurses was a core program in the first Education Resource Center in the United States. PMID- 2198044 TI - Lyme disease: facts & essential assessments. AB - This review will encompass a description, pathogenesis, nursing assessments, lab studies, and interventions related to Lyme Disease. Contemporary research will be utilized to provide additional detail for the interested reader. PMID- 2198045 TI - [The Pharmacia CAP system as a new measure of specific IgE. Application in the diagnosis of hypersensitivity to the venom of the Vespula wasp]. AB - Every improvement can make the measurement of specific IgE more effective. This is the case with the CAP system, a new solid phase technique which uses an Immunocap made from hydrophilic polymer, encased in a capsule, for the fixation of anti-IgE or allergen. The Immunocap fixes 3 times more protein than paper discs. Another improvement is that of calibration of the CAP System by the WHO standard for IgE, with the results expressed in KUI/I: 0.35 to 100 KUI/I for specific IgE and 2 to 2,000 KUI/I for total IgE. The study was of patients who had an anaphylactic or systemic reaction after wasp stings. The subjects were divided into two groups A and B and compared with a reference Groupe C. The study also included subjects who were sensitive to mites, grass pollens and egg. Finally, the technique itself was submitted to a reproducibility test. The results confirm that the sensitivity and specificity of the test were both equal to unity. The CAP System therefore offers the possibility of detecting the lowest amounts of IgE. PMID- 2198046 TI - Mononuclear cell subpopulations in human follicular fluid from stimulated cycles. AB - The study of lymphocyte subsets from human follicular fluid (FF) provides an opportunity to evaluate immunological features of the ovary. We investigated the mononuclear cell subsets in FF and peripheral blood obtained at the time of laparoscopy from ten in vitro fertilization (IVF) patients. Midcycle nonpregnant peripheral blood was used as the control. A marked increase in the proportion of monocytes (CD14+) was observed in FF. Although FF was enriched with CD8+ lymphocytes, a decrease in the proportion of CD4+ lymphocytes was observed. "Memory" T cells in FF, identified by the CD4+ CD45R- phenotype, predominated over "naive" T cells (CD4+ CD45R+) at a ratio of 2:1, which differs from the ratio yielded by control blood samples (1:1). The percentage of activated T cells (CD3+ HLA-DR+ cell) increased significantly in FF. When lymphocyte subsets were studied in the peripheral blood of IVF patients, changes similar to but less significant than those in FF were found. These data support the concept that lymphocytes play an important role in ovarian physiology. PMID- 2198047 TI - Formaldehyde toxicity--new understanding. PMID- 2198048 TI - Cobalt exposure and cancer risk. AB - Cobalt is a technically important metal, used mainly as a binder in the hard metal industry and as a constituent of many alloys. Cobalt compounds are used as drying agents in paints and laquers. Since ancient times, cobalt compounds have been used as coloring agents for pottery, ceramics, and glass. Soluble cobalt salts interfere adversely with cell division, bind irreversibly to nucleic acids in the cell nucleus, induce chromosome aberrations in plants, and are weakly mutagenic in some in vitro tests with cultured animal cells, bacteria, and yeast. Injections or implantation of cobalt metal, cobalt alloys, and cobalt compounds induced local and sometimes metastasizing sarcomas in rats, rabbits, and mice. Mouse is the least susceptible animal. The only published inhalation study with hamsters exposed to CoO aerosols remained non-positive. Indication of possible carcinogenic effects of cobalt alloys or compounds in human populations has arisen from medical use, in hard-metal industries, and at cobalt production. Unfortunately, confounding by nickel and arsenic is a major problem, and the size of most of the investigated populations has been rather small, so none of the investigations alone gives sufficient evidence of a carcinogenic effect in humans, but taken together there is an indication of a carcinogenic potential that should be explored further. PMID- 2198049 TI - Methods of assessing the effect of drug therapy on quality of life. PMID- 2198050 TI - Paraquat poisoning. An overview of the current status. AB - Paraquat is a bipyridyl compound with no known chronic toxicity or teratogenicity. It is poorly absorbed when inhaled, but causes severe illness when ingested orally, death usually occurring within 2 days of ingestion of 50 mg/kg. At lower doses death may be delayed for several weeks. The toxic compound accumulates in lung tissue where free radicals are formed, lipid peroxidation is induced and nicotinamide adenine dinucleotide phosphate (NADPH) is depleted. This produces diffuse alveolitis followed by extensive pulmonary fibrosis. The most important prognostic indicator is the quantity of paraquat absorbed, as shown by the plasma paraquat concentration. While renal failure will develop in the majority of those patients who eventually die, it may not, if present alone, indicate a fatal outcome. The absence of caustic burns in the upper digestive tract indicates a good prognosis. Treatment of paraquat poisoning remains ineffective, but Fuller's earth, activated charcoal and resins may prevent some absorption of the toxin. When tubular necrosis occurs, renal excretion of the compound decreases rapidly. A 3-compartment pharmacokinetic model has been described following ingestion of tracer doses including a 'deep' compartment for active pulmonary accumulation. Haemodialysis, haemoperfusion and forced dialysis have been attempted, with no clear improvement in survival rates. Superoxide dismutase, glutathione peroxidase, N-acetylcysteine and other 'free radical scavengers' have failed to alter the outcome in poisoned patients. Other theoretical treatments, such as deferoxamine, immunotherapy, NADPH repletion and lung transplantation still require clinical validation. PMID- 2198051 TI - Toxic effects of nonsteroidal anti-inflammatory drugs in overdose. An overview of recent evidence on clinical effects and dose-response relationships. AB - Nonsalicylate, nonsteroidal anti-inflammatory drugs (NSAIDs) can be divided into 4 chemical classes: acetic acids, fenamic acids, oxicams and propionic acids. Most NSAID overdoses result in a benign outcome. Of 50,614 exposures reported to poison centres in the United States in a 2-year period, 131 (0.26%) had a major outcome, with 10 deaths. Despite the generally mild effects reported in large patient series, isolated case reports have documented serious toxicity, such as seizures, hypotension, apnoea, coma and renal failure. The majority of these consequences occur after ingestion of substantial quantities by adults attempting suicide. Rarely, with ibuprofen and piroxicam, children who ingest small amounts in accidental exposure develop serious toxicity. Typical signs and symptoms of NSAID overdose include nausea, vomiting, headache, drowsiness, blurred vision and dizziness. Seizures are rarely documented across all NSAID classes, with the exception of mefenamic acid (where seizures occur in over one-third of cases), or following massive ingestion of other agents. Drugs in the propionic acid group have produced metabolic acidosis, respiratory depression and coma in severe cases. Ibuprofen is the agent with the most published data on overdose, probably because it is available without a prescription in many countries. Symptoms are unlikely after ingestion of 100 mg/kg or less, and are usually not life threatening unless more than 400 mg/kg is ingested. There is some relationship between plasma concentrations and the potential for development of symptoms, but plasma concentrations have no impact on treatment decisions. Treatment of NSAID overdose is entirely supportive. Recent trends in emergency department procedures regarding gastric decontamination are evolving towards the recommended administration of activated charcoal without gastric emptying in patients presenting more than 1 hour after ingestion, although gastric lavage, followed by administration of activated charcoal, may be advisable in patients who present earlier. Home administration of syrup of ipecac is still recommended if treatment is given shortly after ingestion, with a few exceptions: for example, ipecac is contraindicated after ingestion of mefenamic acid or ibuprofen in amounts greater than 400 mg/kg. Urine alkalinisation and diuresis have been recommended to enhance the elimination of NSAIDs, based on a pKa in the range of 3 to 5. However, because the drugs are universally highly protein bound, with little unchanged renal excretion, this technique is not likely to be beneficial. Haemodialysis is also unlikely to enhance elimination, but may be required if oliguric renal failure develops. Multiple dose activated charcoal may be useful in enhancing elimination of NSAIDs with long half-lives, such as piroxicam and sulindac. PMID- 2198053 TI - Risk-benefit assessment of amiodarone in the treatment of cardiac arrhythmias. AB - Cardiac arrhythmias are a cause of significant morbidity and mortality in patients with cardiac disease, and thus represent a major management problem. The recognition that antiarrhythmic drugs have the potential to aggravate as well as to attenuate arrhythmias has prompted clinicians to reconsider treatment strategies and weight the benefits of treatment against the risks. In this context, amiodarone has emerged as an effective antiarrhythmic agent and when used at the lowest effective dose has an acceptable side effect profile. This review focuses on the current clinical usage of amiodarone in a broad variety of cardiac arrhythmias, and addresses the risk-benefits arising from its use. It further discusses the current position of amiodarone in the management of sudden cardiac death. PMID- 2198054 TI - Periodontal regeneration. PMID- 2198055 TI - Fabrication of porcelain crown dies. PMID- 2198056 TI - "Connective tissue fibers of the marginal gingiva--1950" update. PMID- 2198052 TI - Adverse reactions and interactions with theophylline. AB - Despite the trend towards newer therapeutic agents, theophylline continues to play a major role in the treatment of reversible airway obstruction. Clinical use of the drug is complicated by a relatively narrow therapeutic range and a large pharmacokinetic variability between patients. Generally, however, theophylline toxicity is foreseeable and preventable. Most cases can be attributed to either inadvertent or intentional overdosing of the drug. Age, disease state and drug interactions are other factors which may contribute to its toxicity. Nausea, vomiting and tachycardia are common signs of mild theophylline toxicity; seizures, ventricular arrhythmias and hypotension are life-threatening manifestations of severe toxicity which may respond poorly to standard therapy. Although serum theophylline concentration correlates with toxicity in a general fashion, life-threatening adverse reactions are not readily predictable from the drug concentration alone. Treatment of theophylline toxicity primarily involves supportive care along with gastric lavage and administration of activated charcoal to facilitate drug removal. The early use of haemoperfusion may be life saving in cases of severe toxicity. PMID- 2198057 TI - Efficacy of a prebrushing rinse in reducing dental plaque. AB - A double-blind parallel design controlled clinical trial was conducted to determine the effect of rinsing with Plax prebrushing rinse on supragingival plaque when used alone and when used just after toothbrushing. One hundred-three (103) subjects refrained from oral hygiene measures for 24 hours. Following a baseline plaque examination, subjects were randomly assigned to either a Plax or to a placebo group, rinsed with 15 ml of their respective rinse for 30 seconds, and were rescored for plaque (postrinse evaluation). Subjects then rinsed again with their assigned rinse, brushed immediately with water for 15 seconds, and were rescored for plaque (postbrush evaluation). Rinsing alone reduced plaque from baseline by 9.0% for Plax and by 10.7% for control. Plax and the control rinse followed by brushing both significantly reduced plaque area scores from baseline by 39.6% and 36.3%, respectively. There were no significant differences between Plax and control mouthrinse in reducing plaque area scores, whether used alone (postrinse) or used just prior to brushing for 15 seconds with water (postbrush evaluation). Use of Plax therefore did not increase the plaque removing efficacy of toothbrushing. PMID- 2198058 TI - Effect of a ZOE temporary cement on the bond strength of a resin luting cement. AB - This study was conducted to determine if a eugenol-based temporary cement affected the bond strength of a dual-cure cement to etched enamel. Dicor buttons were cemented to etched enamel surfaces after pretreatment with a non-eugenol containing cement, a eugenol containing cement and a control. This study concluded that shear bond strengths were unaffected by the temporary cement, provided the enamel surface was cleaned with pumice and etched with 37% phosphoric acid. PMID- 2198059 TI - Calcium binding proteins. Elucidating the contributions to calcium affinity from an analysis of species variants and peptide fragments. AB - This paper describes the sequence homology of calcium-binding proteins belonging to the troponin C superfamily. Specifically, this similarity has been examined for 276 twelve-residue calcium-binding loops. It has been found that, in the calcium-binding loop, several residues appear invariant, regardless of the species of origin or the affinity of the protein. These residues are Asp at position 1 (+X of the coordinating position of the calcium), Asp or Asn at position 3 (+Y), Gly at position 6, Ile at position 8, and Glu at position 12 ( Z). It has also been found that conservation of certain residues can vary in similar sites in similar proteins. For example, position 3 (+Y) in site 3 of troponin C is always an Asn, whereas in calmodulin the residue is always Asp. This study also examined the calcium-binding affinities of peptide fragments comprising the loop, helix-loop, loop-helix, and helix-loop-helix. These were compared with larger enzymatic or chemically generated protein fragments in an effort to understand the various contributions to the calcium-binding affinity of a single-site versus a two-site domain as found in troponin C and calmodulin. Based on free energy differences, it was found that a 34-residue helix-loop-helix peptide represents about 60% of the binding affinity found in the intact protein. Cooperativity with a second calcium binding site accounted for the remaining 40% of the affinity. PMID- 2198060 TI - Relationship of alcohol production to lipid composition of yeast in a continuous flow bioreactor. AB - Saccharomyces cerevisiae was cultivated in a controlled aerated, dual-stage (column), continuous flow bioreactor in a hybrid free-cell and immobilized-cell state. The yeast cells maintained an ethanol concentration of 58-64 and 91-98 g/L in stages I and II, respectively. The lipid composition of the cells cultivated under these conditions was correlated to the effects of aeration by interrupting the aeration on days 113 and 266 of continuous operation. Under conditions of aeration or nonaeration, an alternating increase and decrease in the contents of squalene, sterols, and fatty acids of the respiratory-competent and -deficient unattached free cells was observed. The cellular free lipid compositions of the immobilized cells in the aerated and nonaerated conditions were similar and characteristic of respiratory-deficient cells with the exception of the immobilized cells exposed to a higher ethanol concentration (stage II). These cells contained a broader range of sterol components and increased levels of unsaturated fatty acids than immobilized cells at a lower ethanol concentration (stage I). The neutral lipid to phospholipid ratio decreased for respiratory deficient cells with phosphatidylethanolamine and phosphatidylinositol being the principal phospholipids. The data demonstrated the essentiality of the hybrid bioreactor design for continuous long term performance and the importance of maintaining specific yeast lipid constituents for continuous high alcohol productivity. PMID- 2198061 TI - The present and future role of BCG vaccine in tuberculosis control. PMID- 2198062 TI - Cell mass of Mycobacterium bovis BCG estimated by gas chromatography. AB - The presence of additives and large cellular aggregates in freeze-dried BCG vaccines precludes accurate measurement of total cell content by traditional methods. The possibility that extraction and quantitation of a cell membrane fatty acid may provide a suitable means of cell mass determination was tested. The palmitic acid methyl ester peak area determined by gas chromatography was directly proportional to the wet weight of freshly grown Tice-, Pasteur-, and Glaxo-substrain BCG, as well as the dry weight of the ampoule contents after removal of soluble material. Extraction of palmitic acid from Tice BCG vaccine was not appreciably affected by lyophilization and the calculated dry cell mass values of freeze-dried vaccine samples correlated well with particle number. This method, therefore, may be useful in measuring BCG cell mass during all stages of vaccine manufacture and storage. PMID- 2198063 TI - Survival of Mycoplasma hyorhinis in trypsin solutions. AB - The survival of four strains of Mycoplasma hyorhinis in stock solutions of trypsin was tested at 22, 4 and -15 degrees C. Low (10(4)-10(5) cfu/ml) and high (10(6)-10(7) cfu/ml) initial concentrations of each strain were used, each was tested three times. A regular decrease of low and high concentrations (1 log in 10 and 20 min, respectively) was seen at 22 degrees C. At 4 degrees C the low concentrations showed a reduction of about 1 log/h, while apart from one strain high concentrations hardly decreased during the first 6 h and the survival time ranged from 24 to more than 30 h at the end of which there was a reduction of 4 logs. At -15 degrees C low concentrations survived up to 1 week in only one of the three tests, high concentrations survived for more than 12 weeks (reduction 3 logs). These latter results suggest that mycoplasmas may be present in trypsin as clumps, which deteriorate very slowly. A study was also performed to compare the sensitivity of different cultural procedures for detecting mycoplasmas. PMID- 2198064 TI - Progressive fatal dementia (Creutzfeldt-Jakob disease) in a patient who received homograft tissue for tympanic membrane closure. AB - We report the case history of a 54-year-old man who developed a fatal neurological disorder 4 years after a successful tympanoplasty with homograft pericardium. The final diagnosis of this case was Creutzfeldt-Jakob disease. This infectious spongiform encephalopathy is probably caused by a slow virus that can be transmitted by transplantation materials. The possible accidental transmission of Creutzfeldt-Jacob disease by the use of homograft materials in otologic surgery is discussed. PMID- 2198065 TI - The demonstration of choline acetyltransferase activity in cultured vestibular ganglion cells from the fetal rat. AB - Incubation of vestibular ganglion cells from the rat fetus was successfully done demonstrating bipolar and multipolar cells in the cell cultures produced. Further, the presence of choline-acetyltransferase-positive cells was confirmed immunohistochemically. PMID- 2198066 TI - Functions of maternal mRNA in early development. AB - In this review, the types of mRNAs found in oocytes and eggs of several animal species, particularly Drosophila, marine invertebrates, frogs, and mice, are described. The roles that proteins derived from these mRNAs play in early development are discussed, and connections between maternally inherited information and embryonic pattern are sought. Comparisons between genetically identified maternally expressed genes in Drosophila and maternal mRNAs biochemically characterized in other species are made when possible. Regulation of the meiotic and early embryonic cell cycles is reviewed, and translational control of maternal mRNA following maturation and/or fertilization is discussed with regard to specific mRNAs. PMID- 2198067 TI - Paracetamol poisoning in pregnancy: an analysis of the outcomes of cases referred to the Teratology Information Service of the National Poisons Information Service. AB - A study was carried out to investigate the outcome of pregnancy in 115 women who had been exposed to paracetamol overdose. Follow up was obtained in 48 cases. Exposure occurred in all trimesters, and the most striking feature of this series is that the majority of the pregnancy outcomes were normal. None of the mothers died. There were 39 live born infants with no malformation, 14 of whom had been exposed in the first trimester. Four babies, exposed in the third trimester had neonatal problems, but these seem unrelated to paracetamol. There were two live born infants with gross malformations (spina bifida occulta; and cleft lip and palate). However, as the overdoses occurred at weeks 26 and 28 respectively, long after the structural development of these organs, the malformations could not have been caused by the paracetamol. There were two spontaneous abortions, both in the first trimester, which occurred two weeks after the overdose which may be related to the paracetamol. The overall conclusion is that paracetamol overdose per se is not necessarily an indication for termination of pregnancy. PMID- 2198068 TI - Restrictive cardiomyopathy. PMID- 2198070 TI - The decision-making process in child language assessment. AB - The task of assessing a child's language for the purpose of intervention requires the ability to interpret information from a variety of sources. Knowing how that information is to be used during therapy plays an important part in deciding what type of information needs to be collected and how it will be interpreted. There needs to be a plan that will assist the speech therapist in analysing and interpreting most of the data that would be needed when making therapy-related diagnostic statements. A systems approach offers concepts and methods for devising a plan which will outline the necessary decisions. The purpose of this paper is to present, in a flow chart, the questions that need to be asked in the process of assessing a child's language development for the purpose of intervention; to indicate the type of information that would be needed to answer the questions; to state how the information would be interpreted; to suggest the type of tools that would be needed to collect this information; and to outline how the information can be presented so that a greater quantity of data can be summarised and interpreted in a systematic manner. PMID- 2198069 TI - Auditory impressions of the speech of normal elderly adults. AB - Forty speech-language pathologists listened to randomised recorded samples of the 'Grandfather Passage' read aloud by 10 normal elderly male adults, 10 normal young male adults and 6 dysarthric subjects. The speech samples were rated according to the 38 dimensions devised by Darley and colleagues for the study of the dysarthrias. The ratings of the speech of the older adults fell significantly further from 'normal' on a seven-point continuum than those given to the young adults on nine of the dimensions. The most apparent young/old differences involved laryngeal dimensions. Ratings for the normal geriatric subjects resembled those of the dysarthric groups in some respects. Several instances of misclassification of the normal elderly individuals as 'dysarthric' were also observed. PMID- 2198071 TI - The consequences of excess levels of haemopoietic growth factors. PMID- 2198072 TI - The Second Sheffield Psychotherapy Project: rationale, design and preliminary outcome data. AB - The cost-efficiency of psychotherapy research can be enhanced by (a) dissemination of the rationale and design of large-scale investigations whilst still under way, (b) incorporation of process measures within comparative outcome studies, (c) cumulative development of a series of related studies, and (d) sharing of recordings and other data with other investigators. We present the rationale and design, including full details of process and outcome measures, of the second Sheffield psychotherapy project, in which 120 white-collar, professional and managerial employees presenting with major depressive disorder receive either eight or 16 sessions of either prescriptive (cognitive/behavioural) or exploratory (relationship-oriented) therapy in a 2 x 2 design. Ethical considerations prompted the analysis of preliminary outcome data on 48 clients. Results suggested substantial clinical improvement, of similar magnitude for both methods and both durations of treatment, except that exploratory therapy appeared more effective than prescriptive in relation to interpersonal difficulties. Other workers are invited to build collaboratively on this research by making their own process analyses of recordings available from this study, relating these analyses to the existing impact and outcome data, and developing comparable data sets based on the design and initial results of this project. PMID- 2198073 TI - Crosslinking and radiation inactivation analysis of the subunit structure of the pyridine nucleotide transhydrogenase of Escherichia coli. AB - The pyridine nucleotide transhydrogenase of Escherichia coli consists of two types of subunit (alpha: Mr 53,906; beta: Mr 48,667). The purified and membrane bound enzymes were crosslinked with a series of bifunctional crosslinking agents and by catalyzing the formation of inter-chain disulfides in the presence of cupric 1,10-phenanthrolinate. Crosslinked dimers alpha 2, alpha beta and beta 2, and the trimer alpha 2 beta were obtained. A small amount of tetramer, probably alpha 2 beta 2, was also formed. Radiation inactivation was used to determine the molecular size of the transhydrogenase. The radiation inactivation size (217,000) and chemical crosslinking are consistent with the structure (Mr 205,146) being the oligomer that is responsible for biological activity. PMID- 2198074 TI - Functions and relevance of the terminal complement sequence. AB - The terminal complement sequence is initiated upon cleavage of C5 with liberation of C5a anaphylatoxin, and involves the assembly of macromolecular C5b-9 complexes either on cell surfaces or in plasma. Cell-bound C5b-9 complexes generate transmembrane pores that can cause cell death, or they can elicit secondary cellular reactions triggered, for example, by passive flux of calcium ions into the cells. In vivo functions of the fluid-phase SC5b-9 complex have not yet been defined, but the identity of S-protein with vitronectin (serum spreading factor) provokes the anticipation that significant biological functions of this complex do exist. The terminal complement sequence may fulfil protective functions when it is triggered on alien cells that are marked for destruction. Dysregulation in the complement sequence may, however, result in detrimental attack by C5b-9 on autologous cells. Examples include not only autoimmune disease states, but also the activation of complement on dead or dying cells, and bystander attack on blood cells during cardiopulmonary bypass. Methods for detecting and quantifying C5b-9 are outlined, and the potential usefulness of such assays in clinical research is discussed. PMID- 2198075 TI - A randomized multicentric study comparing alternating combination chemotherapy (VCMP/VBAP) and melphalan-prednisone in multiple myeloma. AB - Between January 1985 and December 1988, 386 patients with multiple myeloma were randomized to receive either MP or combination chemotherapy based on alternating cycles of VCMP and VBAP. The major prognostic parameters did not differ significantly between both treatment groups. A significantly higher proportion of objective responses was observed with combination chemotherapy as compared to MP (47.8 vs 32.2, P = 0.01). The median survival for all patients was 33.5 months. So far no significant differences were found when comparing the survival curves from both groups of patients. However, the median survival of MP-treated patients is 26.8 months, whereas the median survival of patients receiving VCMP/VBAP has not yet been reached. The definitive analysis must await the evaluation of all patients entered into the study and a longer follow-up time. PMID- 2198076 TI - Extramedullary plasmacytoma of the testicle. Sonographic appearance and ultrasonically guided biopsy. AB - Extramedullary plasmacytomas of the testis are extremely rare. This is a report of a patient with plasmacytoma of the testicle who also had an extramedullary plasmacytoma of the epipharynx 12 months earlier. Sonography (US) scans showed a heterogeneous mass of the right testicle with hypoechoic echo pattern; ultrasonically guided fine-needle aspiration biopsy (UGFNAB) allowed confirmation of the diagnosis. Immunoperoxidase studies, performed on histologic specimen after a radical right orchiectomy showed a monoclonal staining pattern of intracellular immunoglobulin for IgA-K type. Bone marrow biopsy, skeletal X-ray and immunoelectrophoresis were all within normal limits. The patient was successfully treated by surgery and is still alive with no evidence of disease. PMID- 2198078 TI - The ontogeny of hemispheric specialization: some old hypotheses revisited. AB - This paper re-examines two hypotheses on the ontogeny of hemispheric specialization that long ago fell into disfavor in neuropsychology. It is argued that these hypotheses, equipotentiality and progressive lateralization, may have suffered from misinterpretation that fostered premature acceptance of the developmental invariance view of hemispheric specialization. An alternative view is presented that incorporates both hypotheses within a neurodevelopmental context using anatomical (postmortem) and childhood aphasia data. PMID- 2198077 TI - Neurite outgrowth and proliferation of non-neuronal cells on cryostat sections of adult muscle. AB - Rat spinal cord cells were cultured on cryostat sections of innervated and denervated muscle. Neurite outgrowth was greater on sections of denervated muscle, which therefore appeared to act on in vivo nerve regeneration. It seems that muscle sections were able to release into the culture medium factors that increase proliferation of fibroblasts. The muscle therefore appeared able to modulate its interaction with its environment by acting on different types of cells. PMID- 2198079 TI - Acute administration of estrogen suppresses LH secretion without altering GnRH release in ovariectomized rhesus macaques. AB - The pattern of hypothalamic gonadotropin-releasing hormone (GnRH) release was examined during estrogen (E)-induced suppression of plasma luteinizing hormone (LH) in ovariectomized (OVX) rhesus macaques. In Expt. 1, 4 OVX macaques were fitted with a jugular catheter and a push-pull cannula (PPC) directed into the median eminence (ME). Push-pull perfusion (PPP) was initiated 10 h before and continued for 10 h after subcutaneous estradiol benzoate (EB) injection (42 micrograms/kg b.wt.). In Expt. 2, 4 additional monkeys were subjected to local intrahypothalamic perfusion with estradiol-17 beta (E2, 3 microM) for the last 10 h of a 20-h PPP. In Expt. 2, OVX animals were challenged with 5 micrograms exogenous GnRH 3 h before and 8 h after EB injection to test for changes in altered LH release. Integrated 10-min ME perfusate and intermittent 10- or 60-min peripheral plasma samples were assayed for GnRH and LH by radioimmunoassay and bioassay, respectively. In addition, 2 other OVX macaques that received similar ME-PPC placement were sacrificed 2 days after the completion of a PPP for immunocytochemical labeling of GnRH neurons at the perfusion site. The results show that after EB, hypothalamic GnRH (MBH-GnRH) release remained unaltered while LH levels declined rapidly (Expt. 1). Similarly, intrahypothalamic perfusion of E2 failed to change the pattern of MBH-GnRH release in any of 4 monkeys (Expt. 2). Conversely, plasma LH release in response to exogenous GnRH was greatly reduced after EB (Expt. 3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198080 TI - [Killing of seroresistant plasmid bearing E. coli strains in polymorphonuclear leukocytes]. AB - Killing of 61 seroresistant E. coli strains equipped with virulence plasmids (F, Ent, Hly, Col) and resistance plasmids (R) in polymorphonuclear leukocytes (PMNL) of healthy donors was determined by the cultivation plate and fluorescence methods of phagocytosis. Killing of the control E. coli strain K12 which does not possess any plasmids was studied by the fluorescent method. Compared to the fluorescent method, the cultivation plate method yielded a significantly higher killing rate of the bacteria after opsonization by 5% (p less than 0.05) and concentrated serum (p less than 0.001). Compared to the control E. coli strain K12, the killing rate of seroresistant E. coli strains in PMNL of healthy donors was significantly lower (p less than 0.001). PMID- 2198081 TI - [The in vitro effect of a combination of sulbactam with cephalothin and cefazolin on strains of Escherichia coli and Proteus mirabilis which produce beta lactamase]. AB - The effect of the combination of sulbactam, cephalothin, and cephazolin was studied in vitro on 88 strains of E. coli and 11 strains of P. mirabilis producing beta-lactamases. Quantitative susceptibility of the tested strains to cephalothin was examined by the disk dilution method and the effect of the combinations with sulbactam by the micromethod. The production of beta-lactamases was determined by the qualitative test with the chromogenic substrate PODAC. Of the total number of 160 E. coli strains beta-lactamases were established in 53.3% of the strains. Of the 47 P. mirabilis strains 23.4% were found to produce beta lactamases. The effect of the combinations with sulbactam was assessed as synergistic, additive, indifferent or antagonistic. In the combination of sulbactam in the concentration of 16.0 mg/l with cephalothin and cephazolin a higher rate of synergistic and additive effect was recorded on both strains. In none of the combinations did sulbactam exert an antagonistic effect. PMID- 2198082 TI - Bronchopulmonary effects of endothelin. PMID- 2198083 TI - Determination of histamine in human plasma: the European external quality control study 1988. AB - There is an increasing interest in measuring human plasma histamine levels in various clinical conditions. A variety of 'old' and newly developed techniques are applied to meet this demand. However, the discrepancy between reported reference values for histamine in human plasma measured using this variety of techniques, suggests the existence of a certain degree of inaccuracy and imprecision. We therefore organized an external quality control study on the reliability of current histamine determinations in European laboratories. Three lyophilized plasma quality control samples, in duplicate, covering the normal and pathological range of histamine concentrations (0-45 nmol/l), two different aqueous histamine standard samples and one solvent sample were sent to 10 laboratories for the analysis of their histamine content. The following methods were used: gas chromatography-mass spectrometry (n = 2), enzymatic single isotopic assay (n = 1), fluorometric-fluoroenzymatic assay (n = 3), radioimmunoassay (n = 3) and high performance liquid chromatography (n = 2). The study was performed and evaluated according to the approved recommendations (1983) of the International Federation of Clinical Chemistry (IFCC). The target values +/- s.d. of the three plasma samples were: 39.5 +/- 4.6 nmol/l (CV = 11.6%), 2.3 +/- 2.2 nmol/l (CV = 96%) and 8.9 +/- 1.5 nmol/l (CV = 17%), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198084 TI - Allergy and cot death: with special focus on allergic sensitivity to cows' milk and anaphylaxis. PMID- 2198085 TI - Venous blood platelets decrease during allergen-induced asthmatic reactions. AB - To determine whether circulating platelets alter during asthmatic reactions induced by allergens, we studied nine subjects previously shown to develop an early or dual asthmatic reaction after inhalation challenge with extracts of house dust mite or grass pollen. In each subject, FEV1, circulating platelets and leucocytes were measured before, 15, 30 and 60 min, and 2, 4, 6 and 8 hr after inhalation of allergen and diluent control administered in a single-blind, randomized fashion. The same procedure was repeated in six of the nine subjects after bronchoconstriction induced by methacholine. Each subject developed an early asthmatic reaction after allergen inhalation challenge, which was followed by a late asthmatic reaction in six subjects and by an equivocal late asthmatic reaction in two of them (fall in FEV1 of 15 and 17% respectively). Compared with the control day, circulating platelets significantly decreased during the allergen-induced early asthmatic reaction (P less than 0.025, at 30 min). Platelet counts returned to baseline values within 4 hr and remained steady thereafter both in subjects who did and did not develop a late asthmatic reaction. No changes in platelet counts occurred after bronchoconstriction induced by methacholine. Diurnal increase of leucocyte numbers occurred after challenge with both allergen and diluent control. These results suggest that platelets may be involved in the pathogenesis of allergen-induced asthmatic reactions. PMID- 2198087 TI - [Systems for the delivery of health care]. AB - Re-examining the role of the nurse, the authors remind us of the importance of understanding how our system of health care has evolved, as well as what it holds for the future. Presenting an historical overview of the past 50 years, they discuss concepts related to moving the profession forward and suggest the decade ahead offers key opportunities. PMID- 2198086 TI - Serum levels of IgE-binding factor (soluble CD23) in diseases associated with elevated IgE. AB - Several in-vitro experiments suggest that the low affinity receptor for IgE (Fc epsilon RII) and its soluble fragment (IgE-binding factor, IgE-BF) are multi functional molecules and more particularly that they are capable of regulating the synthesis of human IgE. In an attempt to examine the in-vivo significance of these in-vitro observations, the serum level of IgE-BF was measured in individuals with allergic or parasitic diseases, both associated with an increased production of IgE. IgE-BF was measured by a radioimmunoassay employing two mAbs against Fc epsilon RII (mAbER). We first compared 257 allergic subjects to 172 non-allergic controls matched for age and sex. Statistical analysis of the data, after logarithmic transformation of IgE-BF and IgE values, revealed that despite a great overlap, the allergic subjects had significantly higher levels of IgE-BF. The correlation between IgE and IgE-BF was very weak but significant. Allergic or non-allergic children had significantly higher IgE-BF levels than the corresponding groups of adults; moreover, the inverse correlation between age and IgE-BF levels was significant only in the children and not in the adults. The IgE BF levels were not influenced by gender, by hyposensitization therapy or by treatment with local steroids. Subjects receiving systemic steroids had lower IgE BF levels than untreated subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198088 TI - Significant prolongation of disease-free period gained by oral polysaccharide K (PSK) administration after curative surgical operation of colorectal cancer. AB - To examine the clinical efficacy and the mechanism of action of polysaccharide K (PSK), a protein-bound polysaccharide extracted from a Basidiomycetes fungus, a randomized double-blind trial was performed by administering PSK to 56 patients and a placebo to another group of 55 patients after surgical operations on their colorectal cancers. The rate of patients in remission (or disease-free) was significantly higher in the PSK group than in the placebo group; the difference between both groups was statistically significant at P less than 0.05 by the log rank test. The survival rate of patients was also significantly (P less than 0.05) higher in the PSK group than in the control group. The most significant laboratory finding was that polymorphonuclear leukocytes from PSK-treated patients showed remarkable enhancement in their activities, such as random and/or chemotactic locomotion, and phagocytic activity, when compared with those in the control group. In conclusion, PSK was useful as a maintenance therapy for patients after their curative surgical operations for colorectal cancer. The beneficial effects were probably due to the activation of leukocyte functions as one of the many biological-response-modifying (activities induced by PSK). PMID- 2198089 TI - Idiotype vaccine for tumor by anti-idiotypic antibody prepared against anti (bacillus Calmette Guerin)BCG monoclonal antibody. AB - The anti-idiotypic antibody (Ab2) prepared against the anti-BCG monoclonal antibody (mAb) (Ab1) exhibited potential vaccine activity against Meth A fibrosarcoma that shared a common antigen(s) with Mycobacterium bovis strain bacillus Calmette Guerin (BCG). Mice vaccinated with the anti-idiotypic antibody (Ab2) were protected significantly against growth of the transplanted Meth A tumor (66%), and the presence of anti-(anti-idiotypic antibody) (Ab3) was proved in the Ab2-vaccinated mice by enzyme-linked immunosorbent assay and indirect immunofluorescence analyses using unabsorbed or absorbed sera against the BCG antigen(s) and Meth A tumor cells. This indicated that the anti-idiotypic antibody (Ab2) mimicked the structures of the BCG antigen(s) and behaved as the BCG antigen(s) to induce the Ab1-like antibody (Ab3) in vivo. Presumably the Ab2 induced Ab3 plays a significant role in preventing growth of the transplanted tumor in animals. By contrast, the control mice treated with normal mouse serum failed to inhibit the tumor growth. These results suggest the possible development of a tumor vaccine from the anti-idiotypic antibody (Ab2) prepared against the anti-BCG monoclonal antibody, for tumors sharing a common antigen(s) with Mycobacterium bovis strain BCG. PMID- 2198091 TI - Coronary thrombolysis in women. AB - Acute myocardial infarction (AMI) is a major cause of morbidity and mortality throughout the world. Although the incidence of AMI is higher in men than women, it is responsible for more than 250,000 annual deaths among women within the United States alone. Coronary thrombolysis is the treatment of choice for AMI and reduces mortality rates in both men and women. However, the absolute benefit may be less in women and, in addition, may not be maintained beyond the early postinfarction period. Bleeding complications, including intracranial hemorrhage, may be more common in women, particularly those more than 65 years of age. The author reviews the topic of coronary thrombolysis in women. PMID- 2198090 TI - [Ventricular tachycardia induced by a bent catheter electrode migrated to the pulmonary artery]. AB - The possibility of migration of a transvenous electrode bend in the infundibulum of the pulmonary artery is a very rare complication of permanent pacing. The Authors describe the case of a patient whose transvenous electrode, positioned in the pulmonary artery 5 years after implantation, was presumably the cause of a ventricular hyperkinetic arrhythmia (VT) and of cerebral disturbances (sublipothymia, syncope). The re-position of the electrode removed the arrhythmia thus considerably improving the symptoms of the patient. PMID- 2198092 TI - Percutaneous transluminal coronary angioplasty in women. AB - Percutaneous transluminal coronary angioplasty (PTCA) for coronary artery disease is currently as successful in women as it is in men. Acute and long-term results are similar for both sexes. Differences in the size of the coronary arteries may have accounted for gender differences in earlier series. However, improved PTCA technology has eliminated gender differences in outcome. PMID- 2198093 TI - Hypertension in women. AB - Hypertension is a common disorder which affects over 40 million individuals in the United States alone. Systemic (idiopathic) hypertension is particularly prevalent in elderly women who seem to tolerate this affliction better than their male counterparts. Women with hypertension should be cautioned about the effects of estrogen-containing oral contraceptives which may cause a further elevation in systemic blood pressure. However, postmenopausal estrogen supplementation does not produce adverse effects on blood pressure and, in fact, may offer cardiovascular protection. Renovascular hypertension, particularly as a result of fibromuscular hyperplasia, is more prevalent in women than men. For women, as for men, tobacco abuse and advanced age are associated with an increased prevalence of atherosclerotic renal artery stenosis. PMID- 2198094 TI - Myocardial infarction in women. AB - Cardiovascular disease is the leading cause of mortality in the United States regardless of gender. Women infrequently present with myocardial infarction as the initial presentation of coronary heart disease and have unrecognized infarctions more frequently than men. Myocardial infarction in women has a similar clinical presentation as in men, with the exception of an increased incidence of non-Q wave myocardial infarctions. Complications of acute infarction in women are probably similar although the majority of data has been drawn from studies involving predominantly men. Women do however experience more strokes and have less postinfarction pericarditis than their male counterparts. Left ventricular function remains the key prognostic determinant in both sexes. Recurrent infarction is increased in women with resultant elevated mortality rates. However, complex ventricular ectopy following myocardial infarction is not predictive of cardiovascular mortality in women. Early and late survival is decreased in women, an effect probably related to the increase in mean age of women as compared with men. Overall, gender distinctions are not usually made in the majority of studies involving myocardial infarction. As epidemiologic, pathophysiologic and clinical factors may be different regarding heart disease in women, further research in this important area is warranted. PMID- 2198095 TI - Recovery from acute myocardial infarction in women. AB - This paper is a review of the literature on recovery from acute myocardial infarction in women. The topic has been subdivided into three areas for presentation: cardiac rehabilitation, return to work and sexual activity. The exploration of the literature revealed the paucity of research on women, but some comparisons could be made between men and women. Compared to men, women appear to utilize cardiac rehabilitation programs less frequently than men and have higher dropout rates, they return to work less frequently and after a longer period of time and resume sexual activity after a longer period of time reporting more symptoms during and after the activity. Investigation of the literature showed that the recovery period for women is incompletely explored and that there is a critical need for research. PMID- 2198096 TI - Cardiovascular disease in women: scope of the problem. AB - Coronary heart disease (CHD) is a major health problem in both men and women. Each year over 250,000 women in the United States alone die as a result of CHD, many of them suddenly. Women sustaining an acute myocardial infarction have a poor in-hospital and long-term prognosis, with a high incidence of stroke, congestive heart failure, nonfatal reinfarction and cardiac death. PMID- 2198097 TI - Congestive heart failure in women: focus on heart failure due to coronary artery disease and diabetes. AB - Congestive heart failure (CHF) is an important clinical syndrome. Evidence from several observational studies suggests sex-related differences in the incidence and prognosis of CHF, particularly in the setting of coronary artery disease. Women appear to be more prone than men to develop heart failure late after myocardial infarction as well as in the peri-infarction period. Additionally, diabetes mellitus appears to promote heart failure to a greater extent in women than in men. PMID- 2198098 TI - Coronary heart disease risk factors in women. AB - Although men and women share a number of coronary risk factors including age, hypertension, cigarette smoking, diabetes, obesity, plasma lipoprotein concentration, and family history, the overall impact of these factors on the incidence and clinical manifestations of coronary heart disease (CHD) may differ. Additional risk factors which solely impact upon women include the use of oral contraceptives, menopause, and postmenopausal hormones. The impact of psychosocial and behavioral factors on CHD risk in women requires further investigation given that our current knowledge of traditional risk factors alone inadequately predicts all cases of CHD. PMID- 2198099 TI - Cerebrovascular disease and stroke in women. AB - There are many special conditions which may predispose women to have a higher risk of stroke. These conditions include pregnancy and the puerperium, exogenous estrogen use, cerebral vasculitis, mitral valve prolapse and migraine. Recognition that certain stroke syndromes are more likely to affect women may aid the clinician in determining the optimal management of cerebrovascular disease and stroke in women. PMID- 2198100 TI - Noninvasive diagnosis of coronary heart disease in women. AB - Coronary heart disease (CHD) is the leading cause of death in the United States accounting for over 600,000 deaths and 1 million hospital admissions each year. Although the overall prevalence of disease is lower in women than in men, one quarter of all deaths in women is caused by CHD. Observations in clinical practice have uncovered a number of interesting facts regarding CHD in women. Despite pathoanatomic similarities in atherosclerotic coronary arteries of men and women, the clinical presentation of CHD frequently differs. Furthermore, the diagnostic approach and interpretation of findings, particularly those yielded from noninvasive tests, may be different, at times drastically so. In this review, the authors discuss the current noninvasive strategy for diagnosing CHD in women. PMID- 2198101 TI - Antithrombotic therapy in the primary and secondary prevention of coronary related death and infarction: focus on gender differences. AB - Much of our understanding of the role of antithrombotic therapy for postmyocardial infarction patients comes from studies which often included few or no women. Despite this shortcoming there are data available which identify gender differences in risk factors, presentation, natural history and treatment results for myocardial infarction. The use of anticoagulants and antiplatelet agents in the prevention and management of myocardial infarction has evolved over 30 years of investigation. The major randomized, controlled and blinded studies of antithrombotics and myocardial infarction are reviewed, with special emphasis on the female population. PMID- 2198103 TI - An overview of removable partial overdentures. AB - As an alternative to complete dentures, overdentures are well established as a sound therapeutic modality for patients with terminal dentition. By utilizing natural tooth roots and their periodontal structures to aid in support, overdentures maintain proprioceptive mediation and a mechanism for masticatory force vectors that favor bone retention over bond resorption. The degree of stability enhancement and denture retention from retained roots varies with the design and environment of the prosthesis. This article reviews various aspects of removable partial over-denture use. PMID- 2198102 TI - Long-acting local anesthetics: a review of clinical efficacy in dentistry. AB - Two long-acting local anesthetics, bupivacaine and etidocaine, have been added to the dental armamentarium. The efficacies, onset times, durations, and hemostatic characteristics of these agents have been well described for a variety of clinical applications. Assessments of their usefulness in managing postoperative pain following oral surgery, endodontics, and periodontics have also been published. This article reviews the clinical utility of these agents and provides recommendations for their safe use in dentistry. PMID- 2198104 TI - An unusual presentation of a silicone implant as a prosthetic complication. AB - This article explores a case of migration and bony cavitation of a silicone implant on the lateral border of the mandible and its prosthetic implications. PMID- 2198105 TI - Burning mouth symptoms: a clinical review, Part I. AB - The multiple etiologies proposed in the literature for burning mouth symptoms (BMS) make definitive clinical diagnosis and treatment difficult. Proposed etiologies can be divided into local systemic, and psychogenic factors. Part I of this two-part article provides a review of the BMS literature focusing on local etiological factors and possible approaches to their treatment. PMID- 2198106 TI - Vital tooth bleaching: the White and Brite technique. AB - A new system of vital and nonvital teeth bleaching is a cosmetic and conservative method of treating dentition discolored by ingested substances, trauma, or other causes. The system also allows individuals with normal range dentition to whiten their teeth to meet cosmetic demands. This article reviews the literature, examines the effects of conventional teeth bleaching techniques, presents a new method for bleaching vital and nonvital teeth, and discusses the impact of new methods on the science of teeth whitening. PMID- 2198107 TI - Contraindications in the use of the periodontal ligament injection. AB - How many times have practitioners used a periodontal ligament injection as a last resort or even in preference to the standard subcutaneous injection? In the past 5 years, the periodontal ligament injection has been implicated in compromising pulpal blood flow, damaging the developing crowns of underlying subcedaneous teeth, causing an increase in systemic absorption of epinephrine from the anesthetic solution, and causing resorption of the cementum. This article discusses some of the disadvantages concerning the periodontal ligament injection in view of some recent research findings. PMID- 2198108 TI - Burning mouth symptoms, Part II: A clinical review. AB - Part I of this series presented a review of the literature on Burning Mouth Symptoms (BMS) focusing on its prevalence, its symptoms, and proposed local etiologic factors associated with the condition. Part II will focus on the possible systemic and psychological etiologic factors in order to provide the dental clinician with a perspective on the alternative factors that may cause BMS. PMID- 2198109 TI - Oral manifestations of HIV infection, Part I. AB - Several signs of human immunodeficiency virus (HIV) infection, such as candidiasis, hairy leukoplakia, and Kaposi's sarcoma, may first appear in the mouth. The dentist is in a unique position to detect the oral manifestations of HIV infection. The purpose of this review article is to provide the dentist with baseline knowledge concerning the oral manifestations of HIV infection, to help the dentist identify such lesions, and to contribute to the early diagnosis and timely treatment of HIV-positive individuals. PMID- 2198110 TI - Mucous membrane pemphigoid: a case report. AB - A protracted 30-year course of oral mucous membrane pemphigoid, with repeated exacerbations and remissions, is reported in an 83-year-old white woman. Its clinical, microscopic, and immunologic features are discussed in this article for differential diagnosis from other mucocutaneous vesiculo-bullous diseases. PMID- 2198111 TI - Toward a structural and molecular definition of the kinetochore. PMID- 2198112 TI - T-1, a mitotic arrester, alters centrosome configurations in fertilized sea urchin eggs. AB - T-1 induces modifications in the shape of the centrosome at division in fertilized eggs of the North American sea urchin, Lytechinus pictus. Phase contrast microscopy observations of mitotic apparatus isolated from T-1-treated (1.7-8.5 microM) eggs at first division shows that the centrosomes already begin to spread or to separate by prophase and that the mitotic spindle is barrel shaped. When eggs are fertilized with sperm that have been preteated with T-1, the centrosomes become flattened; the spindles are of normal length. Immunofluorescence microscopy using an anti-centrosomal monoclonal antibody reveals that T-1 modifies the structure of the centrosome so that barrel-shaped spindles with broad centrosomes are observed at metaphase, rather than the expected focused poles and fusiform spindle. Higher concentrations of T-1 induce fragmentation of centrosomes, causing abnormal accumulation of microtubules in polar regions. These results indicate that T-1 directly alters centrosomal configuration from a compact structure to a flattened or a spread structure. T-1 can be classified as a new category of mitotic drugs that may prove valuable in dissecting the molecular nature of centrosomes. PMID- 2198113 TI - Tubulin flux in the mitotic spindle: where does it come from, where is it going? PMID- 2198114 TI - Antiparallel microtubule interactions: spindle formation and anaphase B. PMID- 2198115 TI - Calculation of left ventricular wall stress. AB - Chamber-stress equations relate wall stresses to pressure and wall dimensions. Such equations play a central role in the analysis and understanding of heart chamber function. Over the past three decades, several stress equations giving radically different results have been derived, used, and/or espoused. They can be classified into two categories, according to the definition of stress underlying the equation. The stresses in one class of equations are total forces per unit normal area, excluding ambient pressure but including pressure in the wall exerted by more external elements of the wall. The stresses in the other class of equations are fiber-pulling forces per unit normal area, that is, total forces per unit normal area excluding all pressure. The validity of stress equations can be tested at least three ways: 1) Do they predict that the pressure inside a small chamber nested in a larger chamber would be the sum of transmural pressures of the two chambers? 2) Do they satisfy the expectation from Laplace's law that a sphere with a given circular stress and thickness/radius ratio would exert twice the pressure of a cylinder with the same circular stress and thickness/radius ratio? 3) Do they predict that the ratio of principle stresses depends on chamber shape but not on wall/cavity ratio, with the circular/longitudinal stress ratio of a cylinder being 2 and that of a prolate spheroid being between 1 and 2? Stress equations of the first class fail all of these tests by large margins, whereas those of the second class pass all of these tests exactly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198116 TI - Effect of protein intake on regional vascular resistance and reactivity to angiotensin II in the rat. AB - Male Sprague-Dawley rats (200-250 g) were fed low protein (6%) diets (LP rats), high protein (50%) diets (HP rats), or regular rat chow (approximately 16% protein) (control rats) and studied under anesthesia after 2 weeks. Dietary protein intake did not affect mean arterial pressure, but renal blood flow was increased in the HP rats and decreased in the LP rats compared with the control rats. Mesenteric blood flow was not significantly different in the three diet groups. Captopril (10 mg.kg-1 i.v.) had no effect on renal vascular resistance in the HP rat but did reduce the elevated renal vascular resistance seen in the LP rat. Meclofenamate (5 mg.kg-1 i.v.) did not significantly affect renal hemodynamics in either HP or LP rats. Finally, the HP rat exhibited resistance to the systemic pressor, renal, and mesenteric vasoconstrictor effects of angiotensin II. Captopril restored the systemic pressor and the mesenteric vasoconstrictor response but not the renal vasoconstrictor response to angiotensin II. Meclofenamate, on the other hand, restored both the systemic pressor response and the renal vasoconstrictor response. Thus, in the LP rat, the vascular response to angiotensin II remains intact, and renal vasoconstriction appears to be mediated by angiotensin II. In contrast, in the HP rat, the renovascular response to angiotensin II is blunted apparently because of enhanced renal prostaglandin production. However, neither increased renal prostaglandin synthesis nor blunting of the renovascular response to angiotensin II appears to account for the chronic vasodilation seen in the HP rat. PMID- 2198117 TI - Diagnosis of salivary gland dysfunction. PMID- 2198118 TI - Response of plasma immunoreactive active renin, inactive renin, plasma renin activity, and aldosterone to hemodialysis in patients with diabetic nephropathy. AB - Several alterations in plasma active renin, inactive renin (prorenin), and aldosterone have been described in patients with diabetes mellitus. Such changes could be of some importance for patients on hemodialysis treatment, who must undergo severe changes in fluid and electrolyte status during each dialysis session. Therefore we studied the response of renin and aldosterone to hemodialysis in uremic diabetic nephropathy patients, using direct immunometric assays to measure plasma active renin concentration (ARC), inactive renin concentration (IRC), total renin concentration (TRC), plasma renin activity (PRA), and plasma aldosterone concentration (PAC) in 11 male patients aged 39-69 (mean 53 +/- 2) with diabetic nephropathy and 11 male age-matched non-diabetics who had been on maintenance hemodialysis for 1-10 years. Although baseline values of IRC were slightly higher, and values of PAC lower in diabetics compared to non diabetics, the results did not reach statistical significance. During hemodialysis, significant increases in ARC (p less than 0.01), TRC (p less than 0.05), and PRA (p less than 0.01), and a significant decrease (p less than 0.05) in PAC were seen in non-diabetic patients but no significant changes were observed in patients with diabetic nephropathy. IRC did not change during hemodialysis in either group of patients. There were no significant differences in body weight, blood pressure, or electrolyte changes in the two groups. These results suggest an altered response of plasma renin and aldosterone to hemodialysis in patients with diabetic nephropathy compared to non-diabetics. The reduced renin response could not be explained by a defect in conversion from inactive renin, but may be caused by decreased secretion of active renin in these patients. PMID- 2198119 TI - Mental status changes in children receiving glucocorticoids. Review of the literature. AB - Glucocorticoid preparations are used commonly in the treatment of many diseases in children and adolescents. Although their physiologic side of effects have been described well, the psychiatric side effects of these medications have received little attention. Limited data suggest that disturbances of affect and behavior may occur in 25-50% of children receiving glucocorticoid. These steroid-induced mental changes may be underrecognized in children, and yet these changes can have considerable impact on social and psychological functioning and treatment outcome. An enhanced awareness and reporting of this phenomenon by clinicians, parents, and teachers would likely lead to better compliance with treatment, improved outcomes, and greater understanding of emotional concomitants of illness. PMID- 2198120 TI - Neonatal mitral valve endocarditis: diagnosis and successful management. AB - Although still considered to be a rare and mostly fatal illness, the reported incidence of neonatal bacterial endocarditis has increased during the past decade. This parallels the establishment of intensive supportive management of severely ill newborns with multiple medical problems. An extremely difficult diagnostic problem with protean manifestations, the presence of neonatal endocarditis should be vigorously sought in the at risk neonate. The authors report the first known case in America of successfully diagnosed and treated neonatal endocarditis involving the mitral valve. PMID- 2198121 TI - Rhabdomyosarcoma of the testicular appendage in an infant: case report. AB - This is a case report of embryonal rhabdomyosarcoma of the epididymal appendage in a 15-month old infant. It is a rare tumor with a good prognosis when treated promptly. The ultrasound examination showed the testicle to be enlarged but hypo echoic in comparison to the epididymis which was infiltrated with tumor. An inflammatory mass or enlargement of a testicle demands careful diagnosis and appropriate therapy with immediate referral to a urologist if the normal clinical course deviates. Representative images are included. Rhabdomyosarcoma of the testicle or extra testicular scrotal structures is rare. A report in 1983 by Kage et al from Japan revealed two cases of the tumor, however, both were in adult males. This case report is an embryonal rhabdomyosarcoma in a fifteen month old infant which presented with a confusing clinical picture. This case is presented in an effort to alert the clinician to the possibility of a rare, non-germ cell tumor presenting as an inflammatory lesion. PMID- 2198122 TI - Consensus conference evaluates key issues concerning use of intravenous immune globulin. PMID- 2198123 TI - Consensus panel considers adjuvant therapy for colon and rectal cancer, identifies levamisole--fluorouracil as standard in colon cancer. PMID- 2198124 TI - Clinical uses of intravenous immune globulin. AB - The preparation, pharmacokinetics, clinical uses, dosage and administration, and adverse effects of intravenous immune globulin (IVIG) are reviewed. IVIG, which consists primarily of immunoglobulin G (IgG), is initially prepared from pooled human plasma by using the Cohn-Oncley fractionation procedure. Secondary treatments render the preparation suitable for i.v. use. The specific antibody content of IVIG depends on the geographic location of the plasma donors, the product, and the product lot. The metabolism of IgG appears to follow a multicompartmental, first-order process. The half-life of IgG is dependent on the half-lives of the IgG subclasses; three of the four subclasses have half-lives in the range of 23-25 days. IVIG is indicated in the treatment of idiopathic thrombocytopenic purpura (ITP) and as replacement therapy in primary humoral immunodeficiencies (PHI). IVIG has also been used for antimicrobial prophylaxis in bone marrow transplant and burn patients and in patients with malignancies. Patients with HIV infection, cystic fibrosis, neonatal sepsis, and respiratory syncytial virus infection may also benefit from prophylaxis or treatment with IVIG. The recommended dosage of IVIG in ITP is 400 mg/kg/day for two to five days. For the treatment of PHI, the usual dosage is 100-400 mg/kg every three or four weeks. Adverse reactions are often mild and are usually related to the infusion rate. Intravenous immune globulin is a valuable therapeutic tool in several immunodeficiency and autoimmune states, but IVIG products are expensive, and conclusive data on their efficacy in the treatment of many disorders remain to be obtained. PMID- 2198125 TI - Anistreplase: a new thrombolytic for the treatment of acute myocardial infarction. AB - The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of anistreplase in the treatment of acute myocardial infarction (AMI) are reviewed. Anistreplase is an acylated form of the streptokinase-plasminogen complex. Acylation makes the complex temporarily inactive but protects it from neutralization by plasmin inhibitors. After deacylation, which begins immediately after injection, the streptokinase plasminogen complex promotes thrombolysis by speeding the conversion of plasminogen to plasmin. Like other thrombolytic agents, anistreplase induces a systemic fibrinogenolytic state. The plasma half-life of anistreplase, 88-112 minutes, is longer than that of the other thrombolytic drugs marketed in the United States. Anistreplase lyses coronary artery thrombi when given by the intracoronary or i.v. route. I.V. anistreplase is comparable in efficacy to i.v. streptokinase but has not been directly compared with i.v. alteplase. Anistreplase therapy in patients with AMI may help preserve left ventricular function and prolong survival. Anistreplase is comparable in safety to other thrombolytic drugs. Although bleeding has occurred in 4-47% of patients treated with anistreplase, most episodes have been clinically unimportant and have occurred at a vascular puncture site; intracranial hemorrhage has occurred in less than 1% of patients. Cardiac arrhythmia and transient hypotension are common after anistreplase administration. Anistreplase is easy to administer and may be appropriate for use in patients with suspected AMI before hospital admission. The recommended dose is 30 units i.v. given over two to five minutes. Anistreplase is similar in efficacy and safety to other thrombolytic agents in the treatment of AMI. The drug's ease of administration may be an important clinical consideration. PMID- 2198127 TI - Trials and tribulations. PMID- 2198126 TI - Criteria for use of intravenous immune globulin (IVIG). PMID- 2198128 TI - Pressure support ventilation. PMID- 2198129 TI - Dreams and suicidal behaviour. AB - Oneirology, the study and interpretation of dream content, has been part of human experience throughout recorded history. In modern times, the interpretation of dreams has been used as a tool in the practice of psychotherapy for the purpose of developing insight into the individual's intrapsychic and interpersonal relationships. Ringel, Jung, and others have noted that the content of dreams may be used to assess the individual's state of mind with regard to suicidal intent. Litman has noted the difference between dreams related to suicide and dreams expressing the presence of a clinical depression. Death dreams of the elderly may be considered expressions of depressive symptoms, although this conclusion should be approached with caution. Taylor, Sanford, and others have noted that death dreams generally may be considered as the need for transformation within the individual's personality. The author's impressions taken from clinical experience as well as his experience in teaching university-level courses both in dream interpretation and suicidology are also included in this paper. PMID- 2198130 TI - The study of suicide from a feminist perspective. AB - The present paper presents a feminist transformation of the study of suicide, following a stage model proposed by Schuster and Van Dyne for the feminist transformation of research in general: (1) invisible women, (2) the search for missing female scholars or suicide, (3) suicidal women as disadvantaged, (4) suicidal women studied on their own terms, and (5) a genuine transformation of the perspectives guiding the field of study. In particular, it has been suggested that a feminist transformation of suicidology would lead us to focus on attempted suicide as the norm while viewing completed suicide as a failed behavior in which the individual inappropriately died. PMID- 2198131 TI - Was a magic bullet aimed in the right direction? PMID- 2198132 TI - Classification of immediate-type, life-threatening allergic or pseudoallergic reactions. PMID- 2198133 TI - Recurrent pneumothorax in AIDS patients with Pneumocystis pneumonia. A clinicopathologic report of three cases and review of the literature. AB - Spontaneous pneumothorax associated with Pneumocystis carinii pneumonia (PCP) in AIDS patients has been reported with increasing frequency; however, little is known about the causative histopathology. In the past year, we treated three patients with documented PCP subsequently complicated by multiple spontaneous pneumothoraces. All patients underwent open surgical repair. In contrast to traditional pathologic findings of PCP in AIDS, histologic sections of lung from each patient consistently demonstrated an extensive interstitial inflammatory process with destruction of lung tissue primarily involving the periphery of the lung. Subpleural necrosis with bleb formation as well as bullous changes persisted even in the absence of an alveolar filling process. We conclude that the mechanism for pneumothorax in PCP is spontaneous rupture of necrotic lung tissue occurring in a subgroup of AIDS patients in which the interstitial inflammatory response to Pneumocystis has been accelerated. PMID- 2198134 TI - Obstructive sleep apnea treated by independently adjusted inspiratory and expiratory positive airway pressures via nasal mask. Physiologic and clinical implications. AB - Treatment of obstructive sleep apnea with nasal continuous positive airway pressure mandates simultaneous increases of both inspiratory and expiratory positive airway pressures to eliminate apneas as well as nonapneic oxyhemoglobin desaturation events. We hypothesized that the forces acting to collapse the upper airway during inspiration and expiration are of different magnitudes and that obstructive sleep-disordered breathing events (including apneas, hypopneas and nonapneic desaturation events) could be eliminated at lower levels of EPAP than IPAP. To test these hypotheses, a device was built that allows the independent adjustment of EPAP and IPAP (nasal BiPAP). Our data support the hypotheses that expiratory phase events are important in the pathogenesis of OSA and that there are differences in the magnitudes of the forces destabilizing the upper airway during inspiration and expiration. Finally, applying these concepts, we have shown that by using a device that permits independent adjustment of EPAP and IPAP, obstructive sleep-disordered breathing can be eliminated at lower levels of expiratory airway pressure compared with conventional nasal CPAP therapy. This may reduce the adverse effects associated with nasal CPAP therapy and improve long-term therapeutic compliance. PMID- 2198135 TI - Treatment of obstructive sleep apnea. A preliminary report comparing nasal CPAP to nasal oxygen in patients with mild OSA. AB - Nasal CPAP is presently accepted as first-line therapy for obstructive sleep apnea, but a significant minority of patients do not tolerate nasal CPAP. The purpose of this study was to compare the benefits of nasal CPAP, nasal oxygen (O2), and placebo (air) using patients as their own controls. We studied eight men, aged 33 to 72 (mean 57 years), who had mild obstructive sleep apnea. To be eligible for study, patients had to have an apnea plus hypopnea index greater than or equal to 5, plus one or more of the following: blood pressure greater than 150/95 mm Hg, multiple sleep latency test mean score less than or equal to 10 minutes, or significant nocturnal cardiac ectopy. After a baseline study, patients received a month each of nocturnal O2 at 4 LPM and air at 4 LPM, presented in random order. The third month of treatment consisted of nasal CPAP (range 2.5 to 12.5 cm H2O). Patients underwent evaluation at baseline and after each month of treatment. It was concluded that oxygen was more effective in improving oxygenation and hypopneas than is nasal CPAP. However, oxygen did not reduce apneas or improve daytime hypersomnolence as well as nasal CPAP in patients with mild OSA. Oxygen might be considered as an alternate form of treatment for patients who are not hypersomnolent, or as an adjunct to nasal CPAP. PMID- 2198137 TI - An evaluation of flow-volume curves as a screening test for obstructive sleep apnea. AB - We examined flow-volume curves for their potential as screening tests for obstructive sleep apnea (OSA) in 401 patients referred for investigation of snoring. In all patients, we performed nocturnal polysomnography, maximum inspiratory and maximum expiratory flow-volume curves. The curves were examined for two features: 1) presence of flow oscillations (the "saw-tooth" sign), and 2) changes in their configuration that might suggest upper airway obstruction as documented by the expiratory/inspiratory flow ratios calculated at 50 and 75 percent of exhaled vital capacity (FR50 and FR25, respectively). Based on the results of nocturnal polysomnography, the patients were stratified according to severity into apnea groups, and the flow ratios and flow oscillations were compared among these groups. We found that neither the FR50 nor FR25 were significantly different among the groups. Inspiratory and expiratory flow oscillations were seen infrequently (32 patients) and tended to occur in patients with more severe sleep apnea. Neither the flow ratios nor the flow oscillations had good predictive values for snoring or sleep apnea. The sensitivity of the flow volume curve abnormalities ranged between 0 and 14 percent, but the specificity was high, ranging between 93 and 95 percent. We conclude that because of low sensitivity, flow-volume loops are not a useful screening test for the diagnosis of OSA in snoring patients. PMID- 2198136 TI - Erythema multiforme and Stevens-Johnson syndrome. Descriptive and therapeutic controversy. AB - Diagnosis and particularly the management of erythema multiforme and Stevens Johnson syndrome are controversial in medical textbooks and thus in individual cases. In these diseases, fatalities may result from various causes, including secondary infection or visceral organ damage to lung, liver, or kidneys. We present a series of 13 cases managed by one group of physicians which demonstrates the controversy in certain cases, and we review the controversy in the medical literature. Corticosteroid therapy used in this series was considered beneficial in every case by the managing physician and lifesaving in some cases. There were no fatalities in this series. Although the summation may be considered as our opinion only, the frequently suggested "controlled trial of corticosteroid therapy" can probably never be done for ethical reasons, and series such as this will have to establish the standard of therapy. PMID- 2198138 TI - The radiographic appearance of pulmonary nocardiosis associated with AIDS. AB - Pulmonary nocardiosis is a well-described infection in immunocompromised patients; however, it is less well documented in patients with AIDS. The pulmonary manifestation in 21 HIV-positive patients who developed pulmonary infection with Nocardia asteroides is described. The radiographic picture included lobar or multilobar consolidation (52 percent [11/21]), solitary masses (24 percent [5/21]), reticulonodular infiltrates (33 percent [7/21]), and pleural effusion (33 percent [7/21]). Cavitation was common (62 percent [13/21]), and upper lobes were more commonly involved (71 percent [15/21]). Although the radiographic picture is variable, nocardiosis should be suspected in an HIV positive patient who has subacute pulmonary disease with an unexplained lung mass or cavitary lesions. PMID- 2198139 TI - Airway carcinoembryonic antigen concentrations in patients with central lung cancer or chronic bronchitis. AB - To determine the clinical utility of airway carcinoembryonic antigen (CEA) concentrations to distinguish malignant from inflammatory airway disease in patients undergoing bronchoscopy, we determined CEA concentrations by enzyme immunoassay in bronchial washings recovered in 48 subjects, including 20 patients with central lung cancer, 18 patients with chronic bronchitis, and ten nonsmoking patients with a diagnosis of pneumonia or peripheral granuloma. Concentrations of CEA in bronchial washings were standardized by using the total protein concentration in recovered fluid (CEA/TP). Concentrations of CEA were significantly increased in bronchial washings recovered from both patients with chronic bronchitis and lung cancer compared with patients with pneumonia or granuloma (252 +/- 47 ng/mg and 199 +/- 64 ng/ml vs 62 +/- 11 ng/mg, SEM, p less than 0.005). Airway CEA concentrations in patients with chronic bronchitis were somewhat increased compared with concentrations recovered from a cancer-involved airway (252 +/- 47 ng/ml vs 199 +/- 64 ng/mg, SEM, p less than 0.05). Measurement of airway CEA concentrations is not useful in distinguishing malignant from inflammatory airway disease as airway concentrations of CEA may be markedly increased in patients with both conditions. PMID- 2198140 TI - Effects of prostaglandin E1 on oxygen delivery and consumption in patients with the adult respiratory distress syndrome. Results from the prostaglandin E1 multicenter trial. The Prostaglandin E1 Study Group. AB - We wanted to determine the long-term effects of a continuous infusion of PGE1 on DO2 and VO2 in patients with ARDS. Data were obtained from a randomized double blind multicenter trial, which evaluated the effects of PGE1 on survival in patients with ARDS. Patients were stratified according to treatment and outcome: placebo-died (n = 8); PGE1-died (n = 12); placebo-survived (n = 9); and PGE1 survived (n = 8). In the placebo-died group, elevations occurred in VO2, which were associated with increases in O2ext and a constant DO2. In contrast, in the PGE1-died group, elevations in VO2 were associated with increases in DO2 and an unchanged O2ext. In the placebo-survived group, VO2 and DO2 decreased, whereas in the PGE1-survived group, VO2 and DO2 increased; however, O2ext decreased in both of these groups. Since impaired O2ext occurs in ARDS, PGE1-induced elevations in DO2, rather than compensatory increases in O2ext, may achieve better tissue oxygenation. We conclude that although the recently completed multicenter trial failed to show an enhancing effect of PGE1 on survival in patients with advanced ARDS, PGE1 may have important effects on oxygen transport and, therefore, may still have a role in the treatment of early manifestations of ARDS, either alone or in combination with other agents. PMID- 2198141 TI - Oxygen cost of breathing and diaphragmatic pressure-time index. Measurement in patients with COPD during weaning with pressure support ventilation. AB - The oxygen cost of breathing and the time integral of the transdiaphragmatic pressure were measured at the onset of the weaning period in eight patients with chronic obstructive pulmonary disease requiring mechanical ventilation. Measurements were achieved during continuous positive airway pressure ventilation and during 15 cmH2O pressure support ventilation. For both periods, the O2COB was estimated as the difference between oxygen uptake of the period and that during controlled ventilation. During CPAP ventilation, the O2COB was 16.9 +/- 1.5 percent. During PSV, it was only 6.3 +/- 1.3 percent, and PTdi decreased by 73 percent compared to the CPAP period. Both effects illustrate the ability of PSV to facilitate spontaneous breathing during weaning from mechanical ventilation. However, we found these measurements to be of no help in predicting the duration of the weaning process. PMID- 2198142 TI - Propafenone: a promising new antiarrhythmic agent. PMID- 2198143 TI - Current use of imaging in the evaluation of primary mediastinal masses. AB - A wide variety of lesions occur in the mediastinum in patients of every age. Twenty five to 50 percent of these primary mediastinal masses may be malignant, making early diagnosis and therapy crucial. Since most arise from normal structures in the region, localization of lesions to compartments of the mediastinum may assist in diagnosis. This article reviews imaging techniques for lesions originating in the mediastinum. PMID- 2198144 TI - The management of chronic hypoventilation. PMID- 2198145 TI - Fungal infection with non-Hodgkin's lymphoma. PMID- 2198146 TI - School avoidance behavior: motivational bases and implications for intervention. AB - Intrinsic motivational constructs relevant to understanding and ameliorating school avoidance are discussed. Specifically, the concepts of self-determination, competence, and relatedness are highlighted in differentiating proactive and reactive avoidance behavior. From this perspective, five groups are described. Intervention implications are illustrated for proactive and reactive school avoiders, with special attention to strategies for the crucial period of transition back to school. PMID- 2198147 TI - Endorectal ultrasound in the preoperative staging of rectal tumors. A learning experience. AB - The preoperative staging of rectal cancer has important implications for treatment as local therapies become increasingly utilized. Seventy-seven patients underwent preoperative staging using endorectal ultrasonography. All patients had complete pathologic staging and none had preoperative radiotherapy. Depth of invasion of the tumor was accurately predicted in 75 percent of cases in the entire group, with 22 percent overstaged and 3 percent understaged. Accuracy improved greatly over the study period, and in the past six months, 95 percent have been accurately staged for depth of invasion with 5 percent overstaged. Lymph nodes have been properly classified into positive and negative groups in 88 percent of cases in the past year, with a specificity of 90 percent and a sensitivity of 88 percent. Endorectal ultrasound is an accurate preoperative staging modality. Accuracy is improved greatly with increased experience and it has been found that the 5-layer anatomical model facilitates accurate staging. Introduction of the ultrasound probe through a previously placed proctoscope ensures complete scanning of the entire lesion and should be used for the majority of examinations. PMID- 2198148 TI - Intussusception and its relation to rectal prolapse--a 19th century account. PMID- 2198149 TI - Gerodontics: the evolution of a new dental specialty. PMID- 2198150 TI - The epidemiology and immunogenetics of IDDM in Italian-heritage populations. Diabetes Epidemiology Research International (DERI) Study Group. PMID- 2198151 TI - Noninsulin-dependent diabetes mellitus in black and white Americans. AB - This report presents an overview of the prevalence, characteristics, morbidity, mortality, and risk factors for noninsulin-dependent diabetes (NIDDM) in Blacks and Whites in the United States. Data are drawn primarily from national surveys, but the report also includes the few clinical studies that have differentiated the two races. NIDDM constitutes 90-95% of all diabetes in the United States and is more prevalent in Black Americans than in Whites. Diabetes prevalence increases with age for both races and reaches 26% among Blacks aged 65-74 years compared with 18% among Whites. Rates of diabetes among persons aged 20-74 years are 30% higher in White women, 70% higher in Black men, and 100% higher in Black women, compared with White men. Approximately half of diabetes is undiagnosed in both races. White and Black diabetics are similar with regard to age, duration of diabetes, and diabetes therapies, although Blacks of both sexes are more obese than their White counterparts. Rates of vision loss, amputations, and renal disease are 1.5-4 times higher in Blacks than in Whites, although prevalence of hypertension is about equal in the two races. Blacks and Whites see the same physician specialists for their diabetes, but Whites have approximately 40% more visits to office-based physicians each year. Diabetes-specific mortality has declined significantly in the past decade and may now be lower in Black than in White diabetics. Risk factors for diabetes, including age, sex, obesity, and family history of diabetes, all operate within both race groups and probably interact with each other. The effect of gender and family history on rates of diabetes is similar in Blacks and Whites. Blacks have higher rates of diabetes at each obesity level, indicating that obesity alone cannot explain the differential in prevalence between the races. Impaired glucose tolerance (IGT), a strong risk factor for development of diabetes, increases with age in all race/sex groups except for Black women older than 54 years in whom rates of IGT, decline, possibly because of conversion of IGT to diabetes. PMID- 2198152 TI - The epidemiology and natural history of NIDDM--lessons from the South Pacific. PMID- 2198153 TI - The endogenous insulin secretion was suppressed during insulin therapy in NIDDM patients. AB - Urinary C-peptide excretion (U-C-peptide) was measured in order to examine the changes in endogenous insulin secretion after the beginning of insulin therapy. U C-peptide in the 24-h urine (TU-C-peptide) of non-insulin-dependent diabetes mellitus (NIDDM) patients was measured on the 6,7,8th (period-A), 13,14,15th (period-B) and 20,21,22nd day (period-C) after admission. The TU-C-peptide of NIDDM patients, newly receiving insulin therapy from the 9th day, decreased to 58.7 +/- 6.2% (mean +/- SEM) of its basal level (period-A, 19.8 +/- 3.8 nmol/day) at period-B and remained at the same level at period-C, although U-C-peptide in the urine collected between 04.00 h and 06.30 h did not decrease significantly. Their plasma C-peptide levels from 2-5 h after the ingestion of a mixed meal at period-C decreased significantly compared with those at period-A. On the other hand, the TU-C-peptide of NIDDM patients who continued therapy with insulin or sulfonylureas in the outpatient clinic at period-B and -C did not decrease significantly from the basal level at period-A, although fasting plasma glucose decreased to the same level in both groups of patients. These results suggest that the endogenous insulin secretion after food ingestion is suppressed during insulin therapy in NIDDM patients. PMID- 2198154 TI - The relationship of family dynamics/social support to patient functioning in IDDM patients on intensive insulin therapy. AB - A 6 month pilot study was conducted to examine the relationship between family dynamics/social support and patient functioning in diabetic patients on intensive insulin therapy. Intensified therapy was associated with improvements in the DUHP symptom score, MHI psychological well-being score, and in the DUHP social functioning score. In diabetic patients, regardless of therapy, extreme family dynamics were correlated with higher DUHP symptom scores and lower MHI psychological well-being scores at the initial measurement time. However, over the 6 month study period, extreme family dynamics were predictive of improvements in the DUHP symptoms score and in the quality of friendships in diabetic patients on intensive insuline therapy. In diabetic patients, regardless of therapy, higher levels of social support correlated with higher levels of psychological and social functioning at the initial measurement time, and with improvements in quality of family life over the 6 month measurement time. Higher social support was also associated with improvements in quantity of friends and the DUHP social functioning score in diabetic patients on intensive insulin therapy. The study also generated empiric support for co-evolutionary models of disease states/family dynamics/treatment systems by showing that 6 month changes in family dynamics were predicted by the initial FACES adaptability measure and the initial mean monthly glucose value. Intensified therapy predicted lower family cohesion and more family rigidity over the 6 month study period. These findings also suggest, when combined with the result that diabetic patients from more cohesive families experienced a rise in monthly mean glucose values, that some diabetic patients may become trapped in a vicious cycle which perpetuates poor glucose control and extreme family dynamics. PMID- 2198155 TI - Long-term effects of bezafibrate on in vivo VLDL-triglyceride production in the rat. AB - Long-term effects of bezafibrate on in vivo production of VLDL-triglyceride were studied in the rat. Bezafibrate given at a daily dose of 30 mg/kg body weight for 14 days produced a decrease not only in triglyceride by 51% but in cholesterol by 28% and phospholipid by 18%. Despite a marked reduction in plasma triglyceride concentrations, there was no significant change in the rate of VLDL-triglyceride secretion from the liver into the circulation between bezafibrate-treated and control animals (1113 +/- 58 and 1234 +/- 63 micrograms/min, respectively). In addition, bezafibrate produced no change in lipid composition in VLDL. These results suggest that bezafibrate enhances triglyceride removal from the circulation, which leads to reduction in plasma triglyceride. PMID- 2198156 TI - Multicentre double-blind study of the efficacy, safety and tolerance of pirazolac compared with sulindac in patients with rheumatoid arthritis. AB - Of the 160 patients (80 pirazolac/80 sulindac) who entered the study through 14 investigators, three-quarters completed a 12-weeks therapy and three-fifths completed the entire 24-weeks therapy. In the pirazolac group 15% of the patients and in the sulindac group 11% dropped out from the study due to adverse clinical experience. The drop-out rates due to unsatisfactory therapeutic response were respectively 15% and 16% in the pirazolac and the sulindac groups. Both treatment groups showed significant improvement from baseline for all parameters except for the erythrocyte sedimentation rate at weeks 4, 8, 12 and 16 for the sulindac group and weeks 4 and 8 for the pirazolac group. The two treatment groups were comparable as to effectiveness; however, the improvement rates in 36 out of 41 efficacy measurements based on the definition of clinically relevant changes in relation to baseline were estimated to be superior for the group under pirazolac therapy. The rate of improvement for the American Rheumatism Association functional class at the end of the study was 23% in the pirazolac group and 9% in the sulindac group (p less than 0.05). Of the patients in the pirazolac and sulindac groups, 45% and 44% respectively reported no adverse effects at all throughout the whole 24-weeks study. The rates of patients reporting at least one adverse reaction in a body system were not different between the two groups. An exception was the body as a whole where ten patients (12.5%) in the sulindac group and only two (2.5%) in the pirazolac group reported adverse reactions (p = 0.03). No differences occurred between the two treatment groups with regards to intensity, causality or the number of occurrences of adverse clinical experiences. One death in the sulindac treatment group was reported during the study. In both treatment groups, alterations in laboratory tests were minor or negligible or associated with abnormal pre-treatment values and, generally speaking, without any clinical relevance. There were some patients, who had increases from baseline in alkaline phosphate in both treatment groups. However, these were usually transient, occasionally complemented by a slight increase of serum glutamic oxaloacetic acid transaminase. PMID- 2198157 TI - A 12-week double-blind study of the efficacy, safety and tolerance of pirazolac b.i.d. compared with indomethacin t.i.d. in patients with ankylosing spondylitis. AB - A 12-week trial was carried out to compare the efficacy of pirazolac (300-600 mg b.i.d.) with that of indomethacin (25-50 mg t.i.d.) in patients with ankylosing spondylitis. A total of 119 patients completed the treatment period, with 32 drop outs. Both therapies showed significant improvements in clinical symptoms. PMID- 2198158 TI - Virology of the human immunodeficiency virus type 1. AB - Understanding the mode of replication of the human immunodeficiency virus (HIV) is necessary for explaining the natural history of HIV infection and for the development of therapeutic and prophylactic agents. The life cycle of HIV involves infective particles, the attachment of the virus to specific cell receptors, reverse transcription of the viral RNA into DNA by using viral encoded enzymes, integration of the viral DNA into the host genome, use of the host machinery to transcribe and translate viral genes, and the formation of budding particles. Viral encoded genes, regulated by a complex interaction of viral and host proteins with viral sequences, ultimately encode for the viral structural proteins, regulatory proteins, and enzymes necessary for the formation of mature infectious particles. Blocking one or more steps in the viral life cycle and preventing enhancement of virus production are important approaches in the control of HIV. PMID- 2198159 TI - Occupational transmission of human immunodeficiency virus. AB - As the number of patients requiring treatment for HIV-1 infection has increased, there has been increasing concern among health-care providers regarding the risks of occupational infection. Fortunately, this risk is low and may be made lower by adherence to infection-control guidelines. The incidence of occupational infection with HIV-1, risk of transmission in the occupational setting, guidelines regarding the handling and contact with infected blood and body fluids, and the approach to the occupationally exposed worker are reviewed. PMID- 2198160 TI - Pathologic manifestations of acquired immunodeficiency syndrome in the head and neck. AB - Various diseases of the head and neck that appear in association with AIDS have been delineated. These diseases may be the initial manifestations of AIDS or may be part of systemic involvement following HIV infection. Both clinicians and pathologists must be aware of the protean manifestations of AIDS in order to establish an accurate and complete diagnosis. Once the diagnosis is established, therapy, which may potentially enhance the quality of life of the infected individual, can be initiated. PMID- 2198161 TI - Head and neck manifestations of the acquired immunodeficiency syndrome in children. AB - The head-and-neck manifestations of HIV infection in children are very different from those in the adult population. Recurrent bacterial and viral infections are common manifestations, and persistent sinusitis or otitis media should make the otolaryngologist suspicious of HIV infection if the child has been exposed to the virus. Other common problems include mucocutaneous and esophageal candidiasis, recurrent herpes I and II and zoster infections, parotid swelling, and cervical lymphadeopathy. PMID- 2198162 TI - Upper and lower airway manifestations of human immunodeficiency virus infection. AB - Patients with HIV infection can have a variety of infectious, neoplastic, and noninfectious but inflammatory processes that involve their upper or lower airways. Knowledge of these pathologic processes as well as a suitable diagnostic approach are essential to care effectively for these patients. PMID- 2198163 TI - Metered dose pressurized aerosols and the ozone layer. PMID- 2198164 TI - Ventilatory effects of nasal continuous positive airway pressure. AB - Nasal continuous positive airway pressure (nCPAP) improved arterial oxygenation in patients with sleep apnoea as well as those with acute pulmonary processes such as Pneumocystis carinii pneumonia. Despite an expanding pool of clinical information, little if any attempt seems to have been made to see whether nCPAP alters ventilatory patterns. The effect of nCPAP was assessed by respiratory inductance plethysmography in 14 healthy males. nCPAP reduced respiratory rate (14.3 +/- 1.47 to 9.7 +/- 1.98, p less than 0.0001) but increased tidal volume (0.483 +/- 0.090 to 0.602 +/- 0.140 l, p = 0.01). Accordingly, minute ventilation decreased (6.91 +/- 1.20 to 5.64 +/- 0.93 l.min-1, p = 0.0002). Duty cycle (TI/TTOT) decreased from 0.43 +/- 0.04 to 0.35 +/- 0.05 s during nCPAP (p less than 0.0001). Mean inspiratory time and mean expiratory time increased with nCPAP (1.79 +/- 0.19 to 2.20 +/- 0.41 and 2.44 +/- 0.38 to 4.27 +/- 1.07 s, respectively, p less than 0.02), but there were no significant changes in mean inspiratory flow rate or partitioning of rib cage and abdominal/diaphragmatic contributions to tidal volume. We conclude that nCPAP effects ventilatory pattern in a manner similar to that described for expiratory threshold loading; that is, by decreasing respiratory frequency and minute ventilation. nCPAP does not appear to stimulate healthy subjects to increase their level of ventilation. PMID- 2198165 TI - Choline magnesium trisalicylate in patients with aspirin-induced asthma. AB - Treatment of inflammatory diseases of asthmatics can be a serious problem since some patients show intolerance to aspirin and other non-steroidal, anti inflammatory drugs that are cyclooxygenase inhibitors. Salicylates were believed to be well tolerated, but recent reports have demonstrated that diflunisal and salicylsalicylic acid can precipitate asthma attacks in aspirin-intolerant patients. This study was designed to determine the tolerance of choline magnesium trisalicylate (CMT), a nonacetylated salicylate with potent analgesic and anti inflammatory activity, in 23 asthmatics with aspirin hypersensitivity confirmed by oral challenge. The study consisted of three phases: 1) patients received increasing doses (50-1,500 mg) of CMT under a single-blind protocol; 2) patients received either a placebo or CMT challenge in a double-blind, randomized, cross over design; 3) patients received CMT at daily 3,000 mg doses for 1 week. Throughout the study, pulmonary function tests, peak nasal inspiratory flow, and serum salicylate and thromboxane B2 (TXB2) levels were monitored. Results showed no airway obstruction, nasal congestion or rhinorrhea after CMT. There was no significant decrease in serum TXB2 levels, indicating the absence of cyclooxygenase inhibition with CMT. We conclude that choline magnesium trisalicylate is a safe drug for treatment of different anti-inflammatory disorders in asthmatics with aspirin hypersensitivity. PMID- 2198166 TI - Increased bronchial responsiveness in primary and secondary Sjogren's syndrome. AB - We examined one group of 33 patients with primary Sjogren's syndrome, one group of 17 patients with secondary Sjogren's syndrome, i.e. associated with other connective tissue diseases, and one group of 14 patients with connective tissue diseases but without Sjogren's syndrome. In each patient we obtained chest radiographs and measured lung volumes, carbon monoxide diffusing capacity and airway responsiveness to methacholine. We observed no difference in chest radiograph abnormalities, in lung volumes and in carbon monoxide diffusing capacity among the three groups. However, we found a slight but significant increase of bronchial responsiveness in patients with primary and secondary Sjogren's syndrome compared with patients with connective tissue disorders but without Sjogren's syndrome. Thus PD20FEV1 methacholine was 1.07 mg (1.2) (geometric mean and GSEM) in primary Sjogren's syndrome, 0.91 mg (1.4) in secondary Sjogren's syndrome (NS), and 2.24 mg (1.09) in patients with connective tissue diseases but without Sjogren's syndrome (t = 2.59 and t = 2.8, both p less than 0.05, vs primary and secondary Sjogren's syndrome, respectively). These results show that some patients with Sjogren's syndrome have mild bronchial hyperresponsiveness, which may be related to the specific airway abnormalities of this disease. PMID- 2198167 TI - Prostaglandin E1 enhances the histamine induced stimulation of the mucociliary activity in the rabbit maxillary sinus. AB - Inflammatory mediators are released in the airways during both inflammatory and allergic reactions, and many of these mediators affect mucociliary activity. To discover whether mucociliary activity is changed by a combination of mediators, the interaction between prostaglandins and histamine or methacholine was studied in vivo in the rabbit maxillary sinus. We used a photoelectric technique and recorded frequency changes induced by tested substances. Prostaglandins E1 and F2 alpha (PGE1 and PGF2 alpha) were given as ia. infusions followed by bolus injections of histamine or methacholine. Infusion with PGE1 (0.1 microgram.kg-1) enhanced the stimulating effect of a subsequent injection of histamine (10 micrograms.kg-1), maximum stimulation being 33 +/- 6% compared to 14 +/- 4% after histamine alone (p = 0.02). When the histamine injection was given 20 min after PGE1 no enhancement was observed. PGE1 did not enhance the stimulating effect of methacholine. In contrast to PGE1, PGF2 alpha failed to enhance the effect of histamine. It is proposed that a role of PGE1 is to modify the mucociliary response to other mediators released during inflammatory and allergic reactions. PMID- 2198168 TI - Transplantation of the lung. AB - The introduction of cyclosporine as a highly effective immunosuppressive agent and the development of new techniques for heart-lung and lung transplantation have led to a new treatment for a wide range of fatal cardiopulmonary diseases. Indications for surgery are now becoming clear, together with major contra indications. Suppurative lung disease, such as cystic fibrosis, can be effectively treated by heart-lung transplant (HLT). A whole new field of pulmonary medicine is emerging to provide the physiological monitoring and diagnostic techniques for major complications such as opportunistic lung infection and pulmonary rejection. Obliterative bronchiolitis, a consequence of frequent and severe rejection, still provides a major challenge to the immunological scientist and respiratory physician. Lung transplantation, by disrupting the vascular supply and innervation of the lung, is raising major questions about the generally accepted beliefs of regulation of breathing and pulmonary mechanics. Finally, as the survival rate improves beyond the current 50% at 3 yrs, lung transplantation will perhaps present further challenges to our understanding of the pathogenesis of various diseases such as asthma and cystic fibrosis. PMID- 2198169 TI - The dental assistant in an orthodontic practice. PMID- 2198171 TI - International Dental Hygienists' Federation. Brief history International Liaison Committee/International Dental Hygienists' Federation. PMID- 2198170 TI - The cleft lip and cleft palate child: an overview. PMID- 2198172 TI - [Detection of IgA in diseased skin and serum of patients with psoriasis vulgaris]. AB - Origin and function of IgA in the psoriatic skin are unknown. Including a monoclonal antibody against the secretory component (SC) of the secretory IgA (SIga), we have tried to characterize the IgA in psoriasis. With help of a polyclonal antiserum we found depots of IgA in the skin in 69% of all investigated patients. There was a correlation between the degree of akanthosis and the amount of intraepidermal IgA. In the serum of the psoriasis total IgA was significant increased, but never we found SC-bound SIgA in the skin or elevated levels in serum of patients. PMID- 2198173 TI - [Determination of IgA anti-endomysium antibodies in different tissue substrates]. PMID- 2198175 TI - The clinical implications of absent or reversed end-diastolic frequencies in umbilical artery flow velocity waveforms. AB - We describe the clinical details of 37 pregnancies with loss or reversal of end diastolic frequencies in the umbilical artery, as detected by Doppler ultrasound. This finding is an ominous sign of serious fetal compromise in the majority of cases, with a high incidence of growth retardation, oligohydramnios, preterm delivery and maternal hypertension. However, current knowledge does not indicate when these pregnancies should be delivered. The possible pathophysiology and available literature are discussed. PMID- 2198174 TI - Oral candidosis: an old disease in new guises. PMID- 2198176 TI - The labour of Constanze Mozart--a musical occasion? AB - In the diary of Mary and Vincent Novello it is mentioned that Constanze Mozart has told that the Quartet in D Minor (K 421/417 b) was written by Mozart during her delivery. The evidence for this information is discussed. PMID- 2198177 TI - Early and late germinal matrix hemorrhage may have different antecedents. AB - The time of occurrence of germinal matrix hemorrhage (GMH) in preterm babies might convey information about risk. We compared the risk profile of babies whose GMH was evident on a cranial ultrasonogram before the 12th postnatal hour (i.e., early GMH) to that of babies whose GMH did not become evident until after that time (i.e., late GMH). Overall, the two groups were similar. Babies with early GMH, however, were more likely to have been born after a course of labor (p = 0.03), for the first measurement of arterial blood pH to have been less than 7.2 (p = 0.02), and to have received bicarbonate (p = less than 0.00001). These findings lend support to the view that the risk profiles of early and late GMH are not identical, and also to the view that intranatal and immediate postnatal factors contribute to the early onset of GMH in susceptible babies. PMID- 2198178 TI - Umbilical artery Doppler flow velocity waveforms and maternal prostaglandin E2 and F2 alpha metabolite concentrations during cervical ripening with prostaglandin E2. AB - In 20 women, the umbilical artery flow velocity waveform (FVW) was recorded immediately before and 30-40 min after administering vaginal or extraamniotic prostaglandin E2 to ripen the cervix. Maternal plasma concentrations of prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) metabolites (bicyclo-PGEM and PGFM, respectively) were measured at the time of the Doppler recordings. The administration of prostaglandin E2 was associated with a significant rise in maternal plasma PGFM and bicyclo-PGEM concentrations, but there was no change in the umbilical artery FVW Pulsatility index (PI). These results suggest that cervical ripening with local prostaglandin E2 has no effect on the umbilical artery FVW. PMID- 2198179 TI - Pregnancy complicated by severe Chlamydia psittaci infection acquired from a goat flock: a case report. PMID- 2198180 TI - New perspectives in the function of pituitary folliculo-stellate cells. AB - Classical morphological studies of the folliculo-stellate (FS) cells of the anterior pituitary have suggested that these cells play roles as supporting cells, in metabolism and in macromolecular transport. Over the last 10 years the details of their activity in both trophic and catabolic processes has been clarified, and recent work has demonstrated several transport systems in these cells. Various novel peptides with growth factor or cytokine activity have been identified in FS cells and/or FS cell conditioned media. These recent functional experiments confirm and extend previous morphological and experimental studies, and in addition open new perspectives on the physiological roles of FS cells. PMID- 2198181 TI - Marginal microleakage of resin-retained bridges in association with existing resin composite and amalgam restorations. AB - The aim of this study was to determine the microleakage associated with resin retained bridge retainers cemented over amalgam and resin composite restorations. Cavities prepared on the labial surfaces of bovine incisors were restored with either amalgam or a posterior resin composite. Non-precious nickel-chromium alloy frameworks were then attached to the teeth by use of one of four cements: Conclude, ABC, Panavia Ex, and Superbond. The specimens were then stored for two weeks or six months, thermocycled, and tested for microleakage by use of a radioactive tracer and an autoradiographic technique. The results showed that more leakage was associated with the amalgam restorations than with the teeth filled with resin composite. Leakage scores increased with time with both the amalgam and composite restorations, except for the Panavia Ex and ABC materials, respectively. PMID- 2198182 TI - Correlation among dentin depth, permeability, and bond strength of adhesive resins. AB - Correlations among dentin permeability, dentin depth, and dentin bonding of Scotchbond, Clearfil New Bond, and Superbond C&B were studied in bovine incisor crown segments. Since the dentin surface was prepared on deeper dentin, the permeability of the dentin increased both in the presence of, and especially after removal of, the smear layer. In general, the deeper the dentin, the lower the bond strengths of Scotchbond, Clearfil New Bond, and Superbond C&B. The higher the dentin permeability, the lower the bond strength of Superbond C&B, but there was no simple relationship in the case of either Scotchbond or Clearfil New Bond. The bond strength of Superbond C&B was much higher than those of Scotchbond or Clearfil New Bond at any depth of dentin. Superbond C&B should be considered as both an enamel- and dentin-bonding agent. PMID- 2198183 TI - Effect of ring length and diameter on effective radial setting expansion. AB - It was previously demonstrated that flaring of MOD inlay castings was inversely proportional to the diameters of casting rings. The purpose of this study was (1) to determine if radial setting expansion of investment was primarily responsible for the inverse proportion and (2) to characterize further the fluid mechanics of setting expansion by determination of setting expansion in casting rings of different lengths and diameters. Eight sets of ten MOD inlay wax patterns with radiopaque markers at the axiogingival and axiopulpal junctions were individually invested in plastic casting rings in two groups: (A) 28 mm diameter and 30 mm, 32 mm, 34 mm, and 42 mm long; and (B) 28 mm, 40 mm, 51 mm, and 60 mm diameter and 34 mm long. All specimens were imaged (by xeroradiography) at specific intervals during the setting reaction; dimensions were measured on the images at each interval. In casting rings of different lengths, no significant differences (p greater than 0.05) were found in total effective setting expansion. Because setting expansion in the 28-mm-diameter rings was from 1.3% to 1.5% and diminished proportionately in rings of increasing diameter, setting expansion of investment appears to be the primary determinant of mold expansion. In casting rings of different diameters, significant differences (p less than 0.001) were found in total expansion in an apparent inverse proportion (p less than 0.001). Changes in dimension at intervals were strongly associated with time, and with time combined with diameter (p less than 0.001). PMID- 2198184 TI - HbA1 in assessment of metabolic control in diabetic BB/E rats. AB - Estimations of HbA1 levels have been used to assess long-term glycaemic control in spontaneously diabetic BB/E rats. The degree of metabolic control achieved by once daily insulin injections and continuous insulin infusion by osmotic minipump was compared. Citrate gel electrophoresis of lysed erythrocytes, previously washed and incubated in 0.9% NaCl, gave accurate HbA1 values without interference from either abnormal Hb variants or labile glycosylation products. Over a 12 week period there was no significant difference in the mean random weekly plasma glucose concentrations between diabetic rats maintained on insulin injections or continuous infusion therapy. The HbA1 values in the injection-treated animals remained unchanged throughout the study period (mean +/- SEM = 5.1 +/- 0.1%). Diabetic rats treated by osmotic minipump showed a steady decline in values over the same period (4.1 +/- 0.1%; p less than 0.001 vs injected rats) but levels remained higher than those recorded in non-diabetic control rats (2.9 +/- 0.01%; p less than 0.001 vs pump-treated rats). These differences in HbA1 were reflected in the plasma glucose values obtained during a 30 h glucose profile performed after six weeks of insulin therapy. Diabetic rats on injection therapy showed considerable diurnal variation in plasma glucose concentration (5.5-11.2 mmol/l; mean 8.9 +/- 0.5) but continuous insulin infusion eliminated the fluctuations giving a significantly lower mean glucose level over the 30 h period (7.3 +/- 0.1 mmol/l; p less than 0.005). HbA1 levels show a poor correlation with random plasma glucose estimations (r = 0.43) but provide a simple and accurate assessment of long-term glycaemic control without the need for multiple 24 h glucose profiles. PMID- 2198185 TI - A laser Doppler velocimetry study of the effect of hypoglycaemia on retinal blood flow in the minipig. AB - The effect of acute hypoglycaemia (plasma glucose less than 2.2 mmol/l) on retinal venous blood flow in the minipig has been determined using bidirectional laser Doppler velocimetry and red free retinal photography. In six pigs the mean flow in a retinal vein increased from 19.3 (+/- 2.8 SEM) microliters/min to 29.7 (+/- 7.5) microliters/min during hypoglycaemia (p less than 0.05) with a return to 18.6 (+/- 3.6) microliters/min when euglycaemia was restored. Retinal blood flow is affected by hypoglycaemia or its haemodynamic consequences. PMID- 2198186 TI - Pulsatile glucagon has greater hyperglycaemic, lipolytic and ketogenic effects than continuous hormone delivery in man: effect of age. AB - The present study aimed at investigating the hyperglycaemic, lipolytic and ketogenic effects of small doses of glucagon delivered continuously or in a pulsatile manner. The study was performed in eight healthy young volunteers (24.2 +/- 1.2 years) and in eight healthy aged subjects (69.4 +/- 2.0 years). In all the subjects, endogenous pancreatic hormone secretion was inhibited by somatostatin and only glucagon was replaced. Consequently, the effects of pulsatile and continuous glucagon delivery were studied in conditions of progressive somatostatin-induced insulin deficiency. In both the young and the aged subjects, pulsatile glucagon delivery resulted in increases in plasma glucose, non-esterified fatty acid, glycerol and beta-hydroxybutyrate levels greater than those observed when the same amount of glucagon was delivered in a continuous manner. The net increases in plasma glucose, glycerol and non esterified fatty acid levels were similar between the young and the aged subjects when glucagon was infused continuously; in contrast, the rise in plasma beta hydroxybutyrate in the aged was only about half that observed in the young subjects. Surprisingly, when glucagon was infused in a pulsatile manner, the rises in plasma glycerol, non-esterified fatty acid and beta-hydroxybutyrate levels were all significantly smaller in the aged subjects, while no significant differences were observed in the blood glucose responses. We conclude that, in the presence of somatostatin-induced insulin deficiency, pulsatile glucagon exerts greater effects on blood glucose, plasma non-esterified fatty acid, glycerol and beta-hydroxybutyrate levels than its continuous delivery. In the elderly, the lipolytic and ketogenic, but not the hyperglycaemic, responses to pulsatile glucagon are significantly reduced. PMID- 2198189 TI - Neurophysiological changes during insulin-induced hypoglycaemia and in the recovery period following glucose infusion in type 1 (insulin-dependent) diabetes mellitus and in normal man. AB - Hypoglycaemia (median venous blood glucose 1.8 mmol/l; range 1.6-2.3) was induced by an intravenous infusion of regular insulin in eight patients with Type 1 (insulin-dependent) diabetes mellitus (age 28.0 +/- 7.4 years; mean +/- SD, duration 15.5 +/- 5.1 years) and in 12 age-matched healthy male control subjects. Multi-channel frequency analysis of electroencephalogram (electrophysiologic brain mapping) and recording of P300 and somatosensory evoked potentials were performed before, during and immediately after the hypoglycaemic period. The hypoglycaemia produced a significant increase in low frequency electroencephalographic activity in both groups, most pronounced over anterior regions of the brain. The electroencephalographic activity was normalised immediately after the hypoglycaemic period. The patients with diabetes showed somewhat longer P300 latencies during the initial normoglycaemic examination. Hypoglycaemia caused a marked reduction of the P300 amplitude in both groups of subjects and the amplitude was not restored immediately after normalisation of blood glucose levels. The somatosensory cortical responses were not affected by hypoglycaemia. We conclude that hypoglycaemia results in impairment in cerebral function, as measured by neurophysiological techniques, which is not immediately normalised when blood glucose is restored to normal. PMID- 2198188 TI - Elevated plasma endothelin in patients with diabetes mellitus. AB - Plasma concentrations of endothelin, a vasoconstrictor peptide released from vascular endothelial cells, have been measured by radioimmunoassay in 100 patients with diabetes mellitus and 19 healthy subjects. The plasma immunoreactive-endothelin concentrations were found to be greatly raised in the patients with diabetes (1,880 +/- 120 fmol/l, mean +/- SEM) compared with the healthy subjects (540 +/- 50 fmol/l, p less than 0.005). The elevation of immunoreactive-endothelin could not be explained by secondary changes in blood pressure or renal disease and did not correlate with the presence of diabetic retinopathy, duration of diabetes mellitus, fasting blood glucose or serum fructosamine. Fast protein liquid chromatographic analysis of the diabetic plasma immunoreactive-endothelin showed three forms, one in a very big molecular weight position, one intermediate and one in the position of endothelin-1 itself. No material appeared in the positions of endothelin-2 and 3. Chromatographic analysis of normal plasma showed only the big molecular weight peak while material in the endothelin-1, 2 or 3 positions was below detection. The elevation of endothelin in diabetic patients may be a marker of, and further exacerbate, their vascular disease. PMID- 2198190 TI - [Sickle cell disease and pregnancy]. AB - Three million out of 4.5 million foreigners in Germany are from countries, where sickle cell anaemia is found. Today, this disease occurs in Germany with sufficient frequency and this makes it imperative for every physician to be familiar with it. Most of the sickle cell patients today attain the reproductive age. During pregnancy, sickle cell patients need very thorough medical care, because of the high foetal and maternal morbidity in this patient group. The main features of sickle cell disease are discussed and a survey of complications in pregnant sickle cell patients is presented. Suggestions are made regarding contraception and prenatal care. PMID- 2198187 TI - Islet amyloid polypeptide in diabetic and non-diabetic Pima Indians. AB - Islet amyloid may have a pathological role in the development of Type 2 (non insulin-dependent) diabetes mellitus. The prevalence of islet amyloid has been investigated on post-mortem pancreatic tissue from both diabetic and non-diabetic Pima Indian subjects who had previously been assessed by oral glucose tolerance tests. Islets were examined for amyloid deposits and for cellular immunoreactivity to pancreatic hormones and islet amyloid polypeptide, the constituent peptide of islet amyloid. Twenty of 26 diabetic subjects (77%) had islet amyloid, compared with one of 14 non-diabetic subjects (7%). Twelve of the diabetic subjects (46%) had amyloid in more than 10% of their islets, whereas only 4% of islets were affected in a single non-diabetic subject. Positive immunoreactivity for islet amyloid peptide was present in the islet amyloid and in islet cells in 54% of the diabetic and 50% of the non-diabetic subjects. Islet amyloid in diabetic Pima Indians may indicate a primary Beta-cell defect which interacts with insulin resistance to produce diabetes, or may develop as a result of Beta-cell dysfunction induced by insulin resistance and hyperglycaemia. PMID- 2198191 TI - [The Arabin cerclage pessary--an alternative to surgical cerclage]. AB - During 1986-1988, the Arabin-cerclage pessary was used alternatively to surgical cerclage in 58 patients for prophylactic and in 44 cases of therapeutic indications. In 5 additional patients, the pessary was applied instead of emergency cerclage. The advantages of the cerclage pessary compared to other rigid pessary types, are based on its flexibility and adjustment to the anatomic conditions of vagina and cervix. The bowl-shaped pessary is inserted with the curvature upwards and the cervix is fixed in the central opening of the cerclage pessary. Thus a constriction, reconfiguration, and elongation of the incompetent cervix is obtained as evidenced by ultrasonography. The only side effect of the pessary treatment is an increase in cervical secretion and subsequent vaginal discharge. No infectious complications occurred. In 92% of the treated gravidae the cerclage pessary could be removed after the 36th week of gestation. Cerclage pessary can be recommended as a favourable alternative to surgical procedures as prophylactic or therapeutic approach, reducing surgical treatment significantly to less than 0.5%. PMID- 2198192 TI - [Surgical correction of uterus abnormalities: experiences with the Tompkins method]. AB - In the last 10 years, 12 abdominal metroplasties (Tompkins) were performed at the 2nd Department of Obstetrics and Gynaecology, Vienna. All patients had a history of at least 2 spontaneous abortions, caused by a deformity of the uterus. The operation according to Tompkins, is technically simple and does not result in a defect in the uterus. There were no intraoperative or postoperative complications. Follow-up was possible in 10 patients, 8 of whom had a persisting wish for a child. 5 of these women became pregnant again, one had an abortion. All children were delivered by elective Caesarean section after the 36th week; the fetal outcome was satisfactory. In our experience, Tompkins' operation is the surgical therapy of choice in habitual abortion cause by Mullerian anomalies. PMID- 2198193 TI - [Iniencephaly: prenatal and postnatal findings]. AB - A 33-year-old para-3 was admitted in the 33rd week of gestation because of a suspected foetal anomaly. Ultrasound examination showed polyhydramnios, exaggerated cervico-thoracic lordosis and significant shortening of the spine because of a reduced number of vertebrae. The facial profile was flat, the foetal movements were rare and slow, and the extremities normal. A biopsy of the placenta revealed a normal female karyotype. Based on ultrasound examination, the diagnosis of iniencephaly was made. Because of the fatal prognosis of this malformation, labour was induced at 35 weeks of gestation. The patient delivered spontaneously. The infant died after 90 minutes. The postmortem examination confirmed the diagnosis of iniencephaly. Iniencephaly is a very rare malformation comprising a bone defect at the occiput, malformation of the cervical and thoracic vertebrae, spina bifida, and retroflexion of the head. The aetiology is not clear. 90% of the probands are female. The malformation is incompatible with survival after birth. PMID- 2198194 TI - [Prenatal diagnosis of type II adenomatoid lung dysplasia]. AB - Congenital adenomatoid malformation of the lung is a rare form of lung disease, characterised by excessive overgrowth of terminal respiratory elements. From the histological as well as the sonographical point of view it can be classified into 3 subtypes. The prognosis depends on the type and the associated malformations. We report on two cases of congenital adenomatoid malformation of the lung type II, diagnosed by ultrasound before the 23rd week of gestation. Criteria that may be useful in the prenatal diagnosis of this malformation are described, and the clinical management is discussed. PMID- 2198195 TI - An examination of periodontal curettes: an SEM study. PMID- 2198196 TI - Interventions in consultation/liaison psychiatry. Part I: Patterns of recommendations. AB - In a previous study, a checklist and a schema for operationalized interventions have been described. In this study, these operationalized interventions have been used in clinical practice in 820 cases. In 287 cases (35%), recommendations focusing on the medical treatment, other than diagnostic action (41%) and medication (68%), were provided. This emphasis on the intensity of medical treatment is an unreported finding. The further distribution of recommendations over the different intervention domains was: obtaining additional psychosocial information, 30%; psychosocial management on the ward, 61%, specifically its organization; discharge planning, 41%; and aftercare management, 24%. Recommendations infrequently used included: monitoring of cognition and behavior, referrals to occupational therapy and alcohol- and drug-related facilities, and a detailed specification of postdischarge care. Since consultee concordance with the consultant's recommendations is important to treatment outcome, this method of a systematic recording of operationalized recommendations is a first step toward enhancing the evaluation of treatment recommended and provided by consultation/liaison (C/L) psychiatrists. Moreover, these operationalized recommendations help advance the specification of protocols for psychiatric intervention studies. PMID- 2198197 TI - Review: thyroid function in psychiatric illness. AB - The development of highly sensitive immunometric assays for thyroid-stimulating hormone (TSH) has provided increased understanding of thyroid hormone regulation but, paradoxically, has contributed to a kaleidoscopic complexity of thyroid function test variability in hospitalized patients with nonthyroidal illness (NTI). In primary hypothyroidism, an elevated TSH is the most sensitive chemical index available, although early cases may show a hyperresponse of TSH to thyrotropin-releasing hormone (TRH) stimulation when the TSH is still within the normal range. The ability of the new TSH assays to discriminate between normal and low levels now allows the diagnosis of thyrotoxicosis to be confirmed by a suppressed TSH in the presence of elevated serum thyroxine (T4) and/or triiodothyronine (T3). The TRH stimulation test is virtually obsolete for the diagnosis of thyrotoxicosis but remains of much interest in the investigation of psychiatric syndromes. Approximately 25% of patients with depression have a blunted TSH response (a rise of less than 5 microU/mL) that differs from thyrotoxicosis, wherein the TSH response is suppressed under 1 microU/mL. The cause of the blunted TSH is uncertain but is not due to hyperthyroidism. In contrast, close to 15% may have a TSH hyperresponse to TRH and/or elevated antithyroid antibodies. Thyroid hormone treatment may benefit the depression in some of these cases. In the sick thyroid state of nonthyroidal illness, a low T3 level is the initial manifestation. In more severe cases, the T4 also falls, the free T4 level in this situation is variable, both normal and low levels being reported from different laboratories. A diagnosis of hypothyroidism requiring treatment with thyroid hormone therapy is unlikely unless there is a concomitant lowfree T4 and elevated TSH in a patient who is not in the process of recovery. In acute psychiatric admissions, there is a high frequency of hyperthyroxinemia. The TSH in these cases is generally either normal or high, suggesting central activation of the hypothalamic-pituitary-thyroid axis. In most instances, the thyroid function tests normalize within 2 weeks, and treatment directed toward the thyroid gland is not indicated. Suppressed TSH levels, usually associated with a normal free T4, has also been described in such patients. Finally, various medications utilized in psychiatric practice have diverse effects on thyroid function and can cause diagnostic difficulty. These include lithium, phenytoin sodium, and carbamazepine, and their effects are reviewed. PMID- 2198198 TI - Should neuroleptic malignant syndrome be treated in a private psychiatric hospital or a general hospital? AB - Neuroleptic malignant syndrome (NMS) has come to be recognized as one of the most serious adverse reactions to neuroleptic therapy. Complications may include cardiopulmonary failure, rhabdomyolysis and renal failure, disseminated intravascular coagulation, infection, dehydration, and shock. This article points out the need for intensive medical management for patients with NMS and questions whether private psychiatric hospitals are adequate to the task. PMID- 2198199 TI - [Carcinogenic nitroso compounds in the industrial environment (review of the literature)]. PMID- 2198200 TI - [Incisura scapulae syndrome]. AB - The suprascapular nerve may rarely be entrapped in the suprascapular notch. This causes weakness of the supra- and infraspinatus muscles and pain in the glenohumeral and acromioclavicular joints, which are innervated by this nerve. The entrapment syndrome may result from direct or indirect trauma, fracture of the neck of the scapula, kinking or traction on a sling affecting the nerve, from the shape of the notch, compression by a ganglion, or its cause may be idiopathic. Diagnosis of the syndrome is based upon deep unceasing pain reported at the postero-lateral shoulder, atrophy of the supra- and infraspinatus muscles, and impaired shoulder external rotation and a lidocaine test. The final proof is taken from polyphasic EMG potentials which are decreased in amplitude and increased in distal latency. Initially the entrapment neuropathy may be treated by immobilization, analgesics, and physiotherapy. A tear of the rotator cuff as well as a frozen shoulder have to be excluded by arthrography. In persistent cases of pain and pathologic EMG findings surgical decompression of the nerve should be done. The trapezius muscle is approached by a postero-superior incision. Via the suprascapular fossa the notch may be reached. Then the nerve is decompressed by removing the transverse scapular ligament. Reports of the cases operated so far are promising, though their number is small. PMID- 2198201 TI - Reverse vascular pedicle hypothenar island flap. AB - The vascular supply of the skin of the hypothenar region was investigated using 12 cadavers and 24 hands. The ramifications of the proper palmar digital artery of the little finger were also investigated by angiogram in 20 hands. It was found that it is possible to raise the hypothenar skin as an island flap, using the reverse vascular pedicle of the proper palmar digital artery of the little finger. We applied this island flap in three cases. With the result of these anatomical and radiological studies, the details of three cases are described. PMID- 2198202 TI - [Microcirculation of the Achilles tendon and significance of the paratenon. A study with the plastination method]. AB - Rupture of a healthy Achilles tendon is disputed. A previous degenerative process with ischemia after recurrent microtraumas is usually held to be responsible. The vascular anatomy of eight human specimens was defined with a new method after perfusion through the femoral artery. This method allows exact analysis of the vessels even at a microscopic level. In contrast with the literature, the authors found a large number of anastomoses between the extra- and the intratendinous vessel system. The well-vascularized paratenon is therefore very important for the nutrition of the Achilles tendon. This fact must be taken into account during the surgical treatment of a rupture. The authors agree with the studies of the anatomist Lang who found a decrease of the intratendinous vascularization in an area 3 to 5 cm above the insertion in the os calcis. However a relationship between the frequency of rupture in this area and the vascular anatomy has not yet been shown. PMID- 2198203 TI - [Direct cyclopexy in cyclodialysis with persistent hypotony syndrome]. AB - We report the results of direct cyclopexy performed on all 16 eyes of 16 patients between 1980 and 1988. The follow-up was 7 months to 95 months (mean 51.4 months). All eyes had developed persistent ocular hypotony following traumatic (15 eyes) or surgical (1 eye) cyclodialysis. The cyclodialyses extended from 45 degrees-255 degrees (mean 120 degrees). Preoperative intraocular pressure was 0 to 8 mm Hg (mean 2.9 mm Hg); preoperative visual acuity ranged from light perception to 20/50. Direct cyclopexy by suture of the insertion of the ciliary muscle to the scleral spur with 10/0 nylon was performed in 16 eyes according to the technique described earlier. In addition, 7 eyes simultaneously underwent the following operative procedures: tectonic keratoplasty (2 eyes), intracapsular cataract extraction and anterior vitrectomy (3 eyes), extracapsular cataract extraction and implantation of a posterior chamber lens (1 eye), and encircling procedure (1 eye). During and after cyclopexy no severe complications were observed. During the immediate postoperative course four eyes developed temporary increased intraocular pressure (26 to 50 mm Hg), which was controlled by medication and was fully reversible. After cyclopexy the cyclodialysis cleft was closed in 15 of 16 eyes with a small persisting cleft (30 degrees) without ocular hypotony persisting in one eye. No new anterior synechiae developed. Visual acuity improved in 14 of 16 eyes (20/80 to 20/20) being 20/40 or better in 10 eyes. In only two eyes was there no improvement in visual acuity as a result of severe traumatic posterior changes. During further postoperative follow-up, the intraocular pressure was below 20 mm Hg in all eyes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198205 TI - [Duration of eyelid suture following tarso-conjunctival transposition]. AB - Temporary closure of the lids is an obvious handicap for elderly tumor patients after the first step of the modified Hughes' tarsoconjunctival flap. So far, it has been suggested that the duration of lid closure should be between 2 weeks and 3 months. We report on 36 patients who were operated on between 1984 and 1989. In 16 patients, the lids were divided after 3 weeks. In another 13 patients, they were divided up to the end of the 5th week postoperatively. Neither dehiscence of the wounds nor tissue necrosis appeared. No progressive lowering of the lid margin occurred. This observation suggests that division of the lids can be performed without risk after 3 to 4 weeks. PMID- 2198204 TI - [Detection of coagulation factor XIII in the vitreous body and periretinal membranes in proliferative retinal diseases]. AB - The human blood coagulation factor catalyses the cross-linking of fibrin monomers at the end of the coagulation cascade. Additional functions are the coupling of fibronectin and collagen to each other and fibrin. Therefore we tried to investigate the significance of factor XIII in the development of intraocular membranes. Using gel electrophoresis and western blotting, both subunits (A and B) of factor XIII could be detected in vitreous aspirates from patients with "idiopathic" proliferative vitreoretinopathy (PVR) (n = 5), traumatic PVR (n = 5), and proliferative diabetic retinopathy (n = 5). In contrast the vitreous of five human "normal" post mortem eyes did not contain the subunits of factor XIII. Furthermore, we observed immunofluorescence staining for both subunits of factor XIII in 20 surgically obtained periretinal membranes. In early cellular as opposed to late hypocellular membranes we observed stronger labeling for both subunits of factor XIII. With double label staining techniques, the fibroblastic cells recognized by vimentin staining did not contain factor XIII. About 50% of the macrophages stained positive for the A-subunit of factor XIII. We observed no labeling for the B-subunit in macrophages. Therefore, we hypothesize that factor XIII in proliferative vitreoretinal disorders (PVR, PDR) is derived from the exudation of plasma and platelets through disrupted blood-retinal barriers. PMID- 2198206 TI - [Vascular tumors of the liver. Morphology, differential diagnosis, prognosis]. AB - A group of 5 primary angiomas of the liver (4 angiosarcomas, 1 cavernous hemangioma) was studied. Classification, differential diagnosis and pathogenesis are discussed. Angiosarcomas may be caused by exposure to thorotrast (2 of our 4 tumors) or of polyvinylchloride. Highly cellular tumors with a herringbone pattern must be differentiated from primarily extrahepatic fibrosarcomas or myosarcomas, and highly cellular solid or medullary tumors from metastasis from a carcinoma or lymphoma. Immunohistology--also in our tumors--permits the identification of angiomas by the demonstration of factor VIII and basement membrane protein, which are negative in other tumors. The binding of lectin Ulex europaeus can also be helpful. The common benign cavernous hemangioma is diagnosed very readily morphologically, but clinical and sonographic diagnosis can be difficult. Its biological significance is to be seen merely in possible rupture and hemorrhage. PMID- 2198207 TI - [Raw food and immunity]. AB - Uncooked food is an integral component of human nutrition, and is a necessary precondition for an intact immune system. Its therapeutic effect is complex, and a variety of influences of raw food and its constituents on the immune system have been documented. Such effects include antibiotic, antiallergic, tumor protective, immunomodulatory, and anti-inflammatory actions. In view of this, uncooked food can be seen as a useful adjunct to drugs in the treatment of allergic, rheumatic and infectious diseases. PMID- 2198208 TI - [Ranitidine in stomach ulcer. Controlled clinical trial of a comparison of administration after the evening meal or before bedtime]. AB - In a randomized, double-blind comparative trial, 44 patients with gastric ulcer received one dose of ranitidine 300 mg following the evening meal (between 17.30 and 20.00 hours), and a placebo tablet just before retiring for the night (21.30 to 23.00 hours) (R-P group). In the comparative group, 43 patients received the same substances in the reverse order (P-R group). After four weeks' treatment, the endoscopic follow-up examinations revealed a 76% healing rate in the R-P group and a 63% healing rate in the P-R group. After six weeks, cumulative healing rates of 98% and 81%, respectively (p less than 0.05) were obtained, showing a better healing effect after early evening ingestion of ranitidine. The number of symptoms recorded at the start of treatment had, after four weeks of treatment, decreased considerably more following early-evening ingestion of ranitidine than after late-evening ingestion (p = 0.05). The results of this trial suggest that, in the treatment of gastric ulcers, the early-evening administration of ranitidine 300 mg is more effective than other modes of ingestion. PMID- 2198209 TI - [Prenatal diagnosis of genetic diseases]. AB - Many severe genetic disorders can be identified in utero to offer parents the option to terminating the pregnancy und preventing the birth of an affected child. Various techniques of gaining tissues or cells for prenatal testings are available such as fetal blood or liver sampling, amniocentesis and chorionic villous sampling (CVS). The first step of the diagnosis is at the cell function level which involves the identification of accumulated or missing metabolites in amniotic fluid by chemical methods. The second step is to study the protein function, biochemical analysis of blood cells, cultured amniocytes and direct or cultured chorionic villi. The third step is the molecular genetic, the deoxyribonucleic acid (DNA) analysis in fetal cells or tissues. The recently developed first-trimester CVS procedure represents a rapid and safe diagnosis in utero. PMID- 2198210 TI - [Gastroesophageal reflux disease]. AB - Gastro-esophageal reflux disease is primarily a functional disorder. Morphological manifestations occur secondarily. Primary functional changes include spontaneous relaxation and insufficiency of the lower esophageal sphincter, delayed gastric emptying and impaired esophageal peristalsis. The diagnosis is established by endoscopy--in special cases by pH-metry. Therapy comprises general measures and specific drug treatment with H2-blockers, omeprazole and prokinetics. Prophylaxis of recurrence is a problem that remains to be solved. PMID- 2198211 TI - [Treatment of uncomplicated urinary tract infections. Effectiveness and tolerance of sultamicillin compared with amoxicillin/clavulanic acid]. AB - In an open, randomized multicenter trial two aminopenicillin/betalactamase inhibitor combinations were compared in 132 patients suffering from acute, uncomplicated urinary tract infections. In each of two groups 66 patients were included. They received 750 mg sultamicillin (STM) b.i.d. and 625 mg amoxicillin/clavulanate (AMX/CLA) t.i.d., respectively. A total of 126 patients who had positive urine cultures prior to therapy were evaluable for effectiveness. In the STM-group, 61 patients (= 95.3%) were cured as compared with 56 patients (= 90.3%) of the AMX/CLA-group. Both combinations were well tolerated; serious side effects were not observed. This study indicates that sultamicillin is as effective and safe as amoxicillin/clavulanate in the treatment of acute uncomplicated urinary tract infections, but with the advantage of b.i.d. dosage. PMID- 2198213 TI - Physiological basis for neuroimmunomodulation. AB - A large number of clinical and experimental observations indicate that immune responses may be modulated by the central nervous system (CNS). The immune system (IS) and CNS are known to communicate via the endocrine and the autonomic nervous systems. In this overview, we will focus on the immunomodulating role of neurotransmitters and neuropeptides. Immune cells appear to express membrane antigens similar to those of neural cells. Similarities re-enforce analogies between CNS and IS cells. The concept that the CNS modulates immune functions implies that the immune system feeds back information to the CNS. In fact, interleukins have neuroendocrine functions whether they are produced at the periphery by immune cells or at the CNS level by glial cells. Finally, the possible endocrine functions of lymphocytes are described and it is suggested that a complete regulatory loop between immune and neuro-endocrine systems exists. Studies in neuro-immunomodulation are of great importance from a theoretical point of view, the CNS-IS inter-relationships may not be considered only between the CNS and the periphery but also at the level of the immune micro environment which may be considered as an immune-neuro-endocrine complex. PMID- 2198212 TI - Failure of aerosolized endothelin (ET-1) to induce bronchial hyperreactivity in the guinea pig. AB - Aerosol administration of endothelin (ET-1) has been shown to provoke a potent bronchoconstriction in the guinea pig. We investigated whether or not, aerosolized ET-1 induces a bronchial hyperreactivity in the guinea pig. Aerosolized ET-1 (10 micrograms/ml for 60 min) did not alter the dose-response curve, established by successive aerosol administration of acetylcholine (ACh) 3 4 h and 18-24 h after challenge with the peptide. In a second protocol, aerosolized ET-1 (10 micrograms/ml for 3 min) induced, in anaesthetized guinea pigs a bronchopulmonary response but did not alter the dose-response curve to aerosolized ACh established 30 min after the challenge. These results suggest that ET-1 may participate to the early, but not the late alteration of the bronchopulmonary tone observed during pathophysiological conditions. PMID- 2198214 TI - Neuropeptide Y: localization in the central nervous system and neuroendocrine functions. AB - Neuropeptide Y (NPY) is a 36-amino acid peptide first isolated and characterized from porcine brain extracts. A number of immunocytochemical investigations have been conducted to determine the localization of NPY-containing neurons in various animal species including both vertebrates and invertebrates. These studies have established the widespread distribution of NPY in the brain and in sympathetic neurons. In the rat brain, a high density of immunoreactive cell bodies and fibers is observed in the cortex, caudate putamen and hippocampus. In the diencephalon, NPY-containing perikarya are mainly located in the arcuate nucleus of the hypothalamus; numerous fibers innervate the paraventricular and suprachiasmatic nuclei of the hypothalamus, as well as the paraventricular nucleus of the thalamus and the periaqueductal gray. At the electron microscope level, using the pre- and post-embedding immunoperoxidase techniques, NPY-like immunoreactivity has been observed in neuronal cell body dendrites and axonal processes. In nerve terminals of the hypothalamus, the product of the immunoreaction is associated with large dense core vesicles. In lower vertebrates, including amphibians and fish, neurons originating from the diencephalic (or telencephalic) region innervate the intermediate lobe of the pituitary where a dense network of immunoreactive fibers has been detected. At the ultrastructural level, positive endings have been observed in direct contact with pituitary melanotrophs of frog and dogfish. These anatomical data suggest that NPY can act both as a neurotransmitter (or neuromodulator) and as a hypophysiotropic neurohormone. In the rat a few NPY-containing fibers are found in the internal zone of the median eminence and high concentrations of NPY-like immunoreactivity are detected in the hypothalamo-hypophyseal portal blood, suggesting that NPY may affect anterior pituitary hormone secretion. Intrajugular injection of NPY causes a marked inhibition of LH release but does not significantly affect other pituitary hormones. Passive immunoneutralization of endogenous NPY by specific NPY antibodies induces stimulation of LH release in female rats, suggesting that NPY could affect LH secretion at the pituitary level. However, NPY has no effect on LH release from cultured pituitary cells or hemipituitaries. In addition, autoradiographic studies show that sites for 125I labeled Bolton-Hunter NPY or 125I-labeled PYY (2 specific ligands of NPY receptors) are not present in the adenohypophysis, while moderate concentrations of these binding sites are found in the neural lobe of the pituitary. It thus appears that the inhibitory effect of NPY on LH secretion must be mediated at the hypothalamic level.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2198215 TI - [Pathophysiologic and diagnostic aspects of heart failure]. AB - Ventricular dysfunction due to an abnormality of the heart which is associated with typical hemodynamic, renal and hormonal reactions, characterizes the clinical syndrome heart failure. The traditional definition of heart failure as the inability to pump an amount of blood sufficient to cover the metabolic needs of the body in the presence of adequate venous return, emphasizes mainly the reduction in cardiac output but not the increase in intracardiac pressures. Pressure or volume overload, decreased contractility, loss of muscle mass or restricted filling represent the most important pathological processes leading to heart failure. The disturbance of systolic ventricular function due to pressure or volume overload or diminished contractility is characterized by a decrease in the ejection fraction, the disturbance in diastolic ventricular function associated with restricted filling is characterized by elevated chamber stiffness. Decreased contractility is most commonly responsible for the development of heart failure. Impairment of diastolic ventricular function can only be regarded as the dominant mechanism leading to heart failure in the presence of a small noncompliant ventricle. Impairment of diastolic ventricular function in an enlarged heart is always associated with an impairment of systolic ventricular function and is, then, relegated to a subordinate role. Common causes of heart failure are coronary artery disease, hypertension, cardiomyopathies, valvular heart diseases and congenital heart diseases, for the incidence of which coronary artery disease is most frequently responsible. Most of these diseases lead to heart failure not via a single, but rather several of the specified pathophysiological processes. Possible mechanisms for loss of contractility include structural changes as well as alterations in excitation-contraction coupling. Possible mechanisms responsible for impaired diastolic ventricular function encompass, in addition to altered calcium flux, structural changes such as fibrosis and hypertrophy and factors such as asynchrony and abnormal loading conditions. With increasing derangement of cardiac function, there is recruitment of the compensatory mechanisms: hypertrophy of the cardiac muscle, Frank-Starling mechanism, activation of the sympathetic nervous system, the renin-angiotensin aldosterone system and the arginine-vasopressin system. The goal is maintenance of adequate blood pressure and cardiac output whereby blood flow is redistributed in favor of the heart and brain and away from the skin, musculature and visceral organs. Activation of the neurohumoral system can lead to excessive vasoconstriction as well as sodium and water retention resulting in an undesired elevation of preload and afterload which, in turn, leads to further worsening of the heart failure.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2198216 TI - [Modification of hemodynamics by angiotensin converting enzyme inhibitors in heart failure]. AB - Challenge to a new therapeutic principle to treat heart failure is to ameliorate or eliminate symptoms, decelerate progression of the disease and reduce mortality. However, to begin, one would request improvement of objective hemodynamic parameters. Angiotensin converting enzyme (ACE) inhibitors may have acute and chronic, global and regional effects. ACE inhibitors acutely and chronically reduce pre- and afterload without reflex tachycardia. They lower myocardial oxygen consumption and improve the relation of coronary blood flow to myocardial oxygen consumption. Cerebral and renal blood flow generally are beneficially influenced if the blood pressure is not lowered too much. Left ventricular dilatation following extensive myocardial infarction which is prognostically unfavourable, may be retarded or prevented by ACE-inhibitors. It is not yet clear whether mortality may thus be reduced as in patients with severe heart failure. Large multicenter studies currently address this question. It is unclear as well whether the effects of ACE-inhibitors are exclusively due to a reduction of circulating angiotensin II. Most likely, interference is of major importance with local renin-angiotensin systems, other hormone systems and the central and peripheral nervous system. PMID- 2198217 TI - [Sympathetic activity in patients with heart failure due to idiopathic dilated cardiomyopathy: effect of ACE inhibitors and other vasodilators]. AB - A decrease in cardiac output in patients with congestive heart failure due to dilated cardiomyopathy is compensated by stimulation of the sympathetic nervous system and the renin-angiotensin-aldosterone system. The increase in plasma norepinephrine and depletion of norepinephrine in the myocardium as well as the disturbance of beta-adrenal and baroreceptor function reflect the limits of the sympathetic nervous stimulation. Together with augmented levels of angiotensin II and vasopressin, this stimulation leads to a significant increase in systemic vascular resistance. Sustained stimulation of at least one of these mechanisms can cause further impairment of the left ventricular function. The severity and prognosis of congestive heart failure due to dilated cardiomyopathy is expressed by the plasma norepinephrine concentration and by its myocardial depletion. Ultimately, activation of the compensatory mechanisms provides the basis for therapeutic approaches: 1. reduction of afterload and systemic vascular resistance and/or 2. diminution of the sympathetic nervous activity. For about the last ten years, ACE inhibitors have been used as pharmacological treatment in addition to positive inotropic and vasodilating substances. Captopril, one of the first orally applicable drugs, reduces left ventricular filling pressure, pulmonary capillary pressure, systemic vascular resistance and increases the cardiac output. Beside the hemodynamic improvement, a decrease in plasma norepinephrine and aldosterone can be observed. Vasodilators and alpha-blocking agents can also reduce afterload and systemic vascular resistance in patients with congestive heart failure due to dilated cardiomyopathy, and may lead to hemodynamic improvement. The main limitations of their long-term application are relatively short duration of action, reflex activation of the renin-angiotensin system due to vasodilation and induction of tolerance. PMID- 2198218 TI - [Treatment of heart failure with calcium antagonists]. AB - Vasodilators have a well-established role in the treatment of congestive heart failure. By virtue of their vasodilating properties, the calcium channel blockers have been advocated for use in the treatment of heart failure, in particular, in consideration of the fact that the left ventricular dysfunction in 60 to 70% of the patients with this condition is due to ischemic heart disease, the primary disorder for which the calcium channel blockers are intended to treat. The net hemodynamic effect of calcium channel blockade is the result of two opposing actions: negative inotropy and systemic vasodilation with reflex-induced sympathetic stimulation. The balance is dependent on the prevailing cardiovascular status prior to administration of the drug. In the presence of no or only mild-to-moderate left ventricular dysfunction and intact adrenergic reflexes, a small amount of negative inotropy is readily offset by afterload reduction and adrenergic stimulation. In the presence of severe left ventricular dysfunction sufficiently extensive to lead to heart failure, a condition in which homeostatic reflexes are already attenuated, even a slight amount of negative inotropy can lead to unequivocal deterioration of hemodynamics. Of the three conventional calcium channel blockers, verapamil exerts the most marked negative inotropic effects. Even verapamil, however, has been shown to lead to hemodynamic improvement in some patients, at least after acute administration. Apparently, the cut-off point between beneficial and adverse actions lies at an ejection fraction between 30 and 40% and a pulmonary capillary pressure of about 20 mm Hg. In patients beyond these limits, if treated with verapamil, worsening of heart failure is not uncommon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198219 TI - [The role of diuretics in the treatment of chronic heart failure]. AB - Altered renal function with renal NaCl-retention can be observed early in the course of congestive heart failure. The afferent pathway of this altered regulation involves changes occurring in the high pressure system as a consequence of foreward failure such as an increase in baroreceptor reflex activity. Efferent pathways may include the renin-angiotensin-aldosterone system, the sympathetic nervous system, prostaglandins, dopamine, ANF, and AVP. At present, the relative importance of these systems in mediating renal NaCl retention in heart failure is still unclear. Expansion of the extracellular fluid volume as a consequence of renal NaCl-retention may, at least acutely, compensate for compromised myocardial function via the Frank-Starling mechanism. As a consequence of volume expansion, chronically increased cardiac preload and possibly afterload may however even aggravate cardiac failure. Diuretics may therefore induce variable effects in patients with congestive heart failure. Acutely, they may ameliorate symptoms of congestion in spite of the possibility of a further decrease in cardiac index. Chronically, they may reduce cardiac pre- and afterload. Through a variety of mechanisms, they may therefore increase cardiac performance in spite of a fall in filling pressures. PMID- 2198220 TI - [Chronic heart failure: effect and evaluation of therapy with positive inotropic substances]. AB - In congestive heart failure (CHF), even today, pharmacotherapy renders primarily only symptomatic improvement. The success of the treatment is basically dependent on the degree of functional myocardial impairment, that is, the condition of the inadequately treatable underlying disease. Treatment should be differentially oriented to the nature of the LV dysfunction as systolic or diastolic whereby the latter may account for 20 to 40% of those with CHF. In the case of diastolic LV dysfunction, because of the impaired compliance, vasodilators are not beneficial since small changes in volume may cause marked changes in filling pressures and vice versa. Additionally, inotropic substances are unfavorable since they further increase filling pressure and impedance, that is, diastolic LV function may become more compromised. For systolic LV dysfunction both vasodilators and positive inotropic substances can be employed. Some unsettled issues remaining include the appropriate time to begin treatment, the most suitable form of combined treatment and the best dosing regimens. Digitalis, as dobutamine, increases measured contractility; those seen to profit from digitalis include symptomatic patients with LV dilatation and impaired pump function as well as patients with supraventricular tachyarrhythmias. Prior to use of positive inotropic drugs in CHF, consideration should be given to whether favorable acute effects can be maintained during longterm treatment, adverse reactions such as arrhythmogenicity are acceptable, and the actions on myocardial oxygen balance. New nonglycoside positive inotropic agents which can also be administered orally, acutely improve hemodynamics; these include catecholamine derivatives, phosphodiesterase inhibitors (PDH). Both substance groups increase contractility but arrhythmogenicity as well, in general via increased concentrations of intracellular cyclic AMP. Reservations regarding the use of positive inotropic drugs for CHF have been supported by the results of studies showing that beta 1 agonists such as prenalterol and beta 2 agonists such as salbutamol or pirbuterol, due to down-regulation of beta-receptor density, are not capable of maintaining improved contractility during chronic treatment; intermittent dobutamine treatment resulted in higher mortality; beta-blockers without intrinsic sympathomimetic activity reduced mortality in patients with CHF after myocardial infarction while on use of beta-receptor blockers with intrinsic sympathomimetic activity, this favorable effect was not observed; during chronic PDH treatment, there was an unfavorable one-year mortality rate (50 to 100%); a controlled study with amrinone did not show a higher mortality than placebo. For most PDH, it is not known with certainty at which therapeutically effective dose the positive inotropic effect can best be realized and whether the acute hemodynamic effects are not predominantly attributable to the vasodilatory properties.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2198221 TI - [How are tachycardic cardiac arrhythmias modified by therapy of congestive heart failure?]. AB - Previous studies have demonstrated the high prevalence of frequent and complex ventricular arrhythmias in patients with severe congestive heart failure. It has been claimed that these arrhythmias are independent risk factors of prognosis. Moreover in severely depressed left ventricular function frequent and repetitive arrhythmias may deteriorate the hemodynamic situation. Recent clinical studies have drawn increasing attention to the possibility that the desired therapeutic effect of Class I antiarrhythmic agents may be complicated by their ability to aggravate the arrhythmia or to provoke new arrhythmias. These "proarrhythmical effects" were more frequent in patients with life-threatening arrhythmias and in those with severely depressed left ventricular function. Prevention trials with Class I antiarrhythmic agents have failed to show beneficial effects on the arrhythmia profile and on the prognosis of those patients. On the other hand, it is now well recognized that the incidence of cardiac death can be reduced by the use of ACE-inhibitors in this patient population. Accordingly, there is evidence of a reduced incidence of complex ventricular arrhythmias during treatment with these drugs in some of the patients with congestive heart failure. The influence of digitalis on the arrhythmia profile and the cardiac mortality in these patients is still a matter of debate. On the other hand, there is evidence that newer positive inotropic agents such as phosphodiesterase-inhibitors rather increase the number of arrhythmias and the prevalence of sudden cardiac death in this patient population. PMID- 2198222 TI - Primary lymphomas of the lung: morphological, immunohistochemical and clinical features. AB - Sixty-two cases of primary malignant lymphoma of the lung were investigated. Fifty-eight lymphomas were of B- and two of T-cell type. Two cases of high-grade lymphoma could not be further classified. The largest group (43 cases) consisted of low-grade B-cell lymphoma of the bronchus-associated lymphoid tissue. These showed features similar to low-grade B-cell lymphomas of the mucosa-associated lymphoid tissue of the stomach. The low-grade lymphomas showed a peak occurrence in the sixth decade, the high-grade lymphomas in the seventh decade. Males predominated slightly. Three-quarters of the patients with low-grade B-cell lymphoma of the bronchus-associated lymphoid tissue showed solitary or multiple sharply defined nodules of the lung. The prognosis of the B-cell-derived lung lymphomas without constitutional symptoms was relatively favourable, regardless of whether they were of low- or high-grade malignancy, whereas patients with constitutional symptoms and the two patients with T-cell lymphomas showed a bad prognosis. However, recurrences and metastases in the lung, stomach, lymph nodes and salivary glands were seen in about 46% of the cases of low-grade B-cell lymphoma of the bronchus-associated lymphoid tissue. PMID- 2198223 TI - Osteoclastoma-like giant cell tumour of the skin. PMID- 2198224 TI - Massive congenital mesenchymal malformation of the lung: another cause of non immune hydrops. PMID- 2198225 TI - Pitfalls in the conception, manipulation, and measurement of visual accommodation. AB - Reports of applied research in visual accommodation frequently contain points of confusion, suggesting that there may be some widespread misunderstanding regarding the nature of accommodation, the complexities involved in its measurement, and the multiple meanings inherent in its terminology. The present paper reviews several of these problem areas. Included are discussions of the effect of refractive error on accommodation assessment; the dangers involved in assuming equivalence among physiological, refractive power, and conjugate distance changes; and multiple meanings in the conception of resting accommodation. A variety of manipulation and measurement problems also are reviewed, including the specification of accommodative target distance, the use of lenses, and the correction of refractive error. The review concludes with recommendations regarding conceptions and procedures useful in avoiding the difficulties described. PMID- 2198226 TI - Selection of the width of the maxillary six anteriors. AB - This article describes an expeditious method to aid in the selection of the combined width of the maxillary six anteriors. A measurement is made on the maxillary cast, from the crest of one pterygomaxillary notch straight across to that on the opposite side of the arch. This number, in millimeters, is used to search a tooth mould chart to find a mould, of the proper facial form, with this approximate combined width when measured laid flat. If the chart shows the measurement on the curve, 5 mm must be added to the notch measurement before referring to the chart. A mould close to this measurement or one that is either one size wider or narrower may be used, based on one's clinical judgement, and the desire of the patient. A survey of 50 consecutive clinical cases showed that when using the notch measurement method 78 percent of the selections were the same or within one mould size of that selected by other techniques. This method is not satisfactory in all situations and more time consuming procedures must then be used. PMID- 2198227 TI - [Etiopathogenesis of malignant melanoma of the skin. I. Clinico-biological and nosologic considerations]. AB - Melanoma incidence is rapidly increasing in several countries. This neoplasm has been consistently studied in patients with dysplastic (pleomorphic) nevus, mainly in Anglo-Saxon populations. There is no evidence that among Italians the sequence pleomorphic nervus----cutaneous malignant melanoma shares the identical pathophysiologic mechanisms with the above mentioned form. Pleomorphic nevi are generally thought to be precursors of malignant melanoma of the skin, due to their chromosomal instability. Also common acquired nevi are lesions which can exhibit, although exceptionally, chromosomal abnormalities. Consequently, the sequence pleomorphic nevus----cutaneous malignant melanoma could also include the common nevus. The clinical implications of this stand-point, however, are to be more extensively investigated. PMID- 2198228 TI - [Etiopathogenesis of malignant melanoma of the skin. II. Disease factors inherent in the organism]. AB - Familial malignant melanoma with dysplastic (pleomorphic) nevus has been the most extensively investigated form of this neoplasm. Searches for dominant oncogenes and tumour recessive genes have been performed in various populations to clarify the pathogenesis of the disease. Some of the them have made in possible to localize the gene of the familial cutaneous melanoma with pleomorphic nevus on 1p chromosome. In various progression stages of this neoplasm different chromosomal abnormalities have been reported, which are only relatively specific of the disease stage. Growth substance (sex steroids, hormones, vitamins, immune factors, ions, prostaglandins, and others) regulate melanocyte proliferation and, perhaps, that of melanoma cells. PMID- 2198229 TI - [Etiopathogenesis of malignant melanoma of the skin. III. Disease factors inherent in the environment. Pathogenetic hypothesis]. AB - Sunlight, particularly its UVB component, is thought to be the most important environmental factor for oncogenesis of melanoma. Its intensity, at the ground level, is a positive function of altitude and a negative function of latitude. Sun exposure and susceptibility in childhood seem to be major risk factors at least in Anglo-saxon countries. UV radiations are able to act as complete carcinogen. Eumelanin/pheomelanin ratio also appears as an important risk factor. Ionizing radiations, heat and traumas have been seldom related to melanoma carcinogenesis. Several chemicals, among them drugs and toxic drugs, add to the list of possible causative agents. Loss of alleles encoding for suppressor factors, caused by UV radiation, might play a significant role in carcinogenesis. A model is proposed, for "mediterranean" vs "caledonian" melanoma, in which the phenotypic sequence melanocytic nevus----melanoma would exhibit peculiar characteristics. PMID- 2198230 TI - [Culture of human normal keratinocytes. Main models and clinical applications]. AB - In the last fifteen years various epidermal cell (EC) culture systems have been developed suitable both for investigation purposes and for clinical applications. In organ and explant cultures skin pieces are grown to obtain in the first case vertical proliferation of epidermis and in the second outward migration and proliferation of EC. In isolated EC cultures, EC suspensions are seeded on plastic or specific substrates (collagens, fibronectin, 3T3 fibroblasts). EC attach to the substrate, proliferate to form a confluent multilayered epithelium and can be subcultured. Using a serum-free medium (MCDB 153) EC can be grown in culture free of any undefined supplement. In organotypical culture systems, EC are seeded on a biological matrix (dermis, dermal equivalent) and lifted at the air-liquid interface. Under these conditions a high level of differentiation of the cultured epidermis can be obtained. The availability of a culture-grown epithelium, similar to the in vivo epidermis, has led to the use of cultured epidermal sheets for the treatment of wounds, in particular burns. The therapeutic results have been quite promising. PMID- 2198231 TI - [Crow-Fukase syndrome (POEMS syndrome). The first Italian presentation of a case and review of the literature]. AB - A 42-year-old Italian man affected with a multisystemic disease is presented. The main features were: polyneuropathy, organomegaly (liver, spleen and lymph nodes enlargement), endocrinopathy (loss of libido, low plasmatic levels of testosterone), monoclonal protein (k-light chains only in 100-fold-concentrated urine sample, without other signs of plasmocytic proliferation), skin changes. Clinical skin alterations were striking: diffuse thickening, hyperpigmentation, hyperhidrosis , hypertrichosis, while histo- and immunopathological examination of skin biopsies showed proliferation of dermal collagen fibers and deposition of melanin in the epidermis. These findings were suggestive for the diagnosis of Crow-Fukase (POEMS) syndrome, associated with peculiar angiofollicular lymph node hyperplasia (Castleman's disease). The patient was followed up for 15 months with steroids, systemic chemotherapy, plasma-exchange and immunomodulating drugs. A massive anasarca complicated the picture leading him to death. Actually the pathomechanisms of this rare disease have not been fully elucidated. The relations between this syndrome and some malignant lymphoproliferative diseases (i.e. osteosclerotic myeloma) are controversial; at least a part of its features could be either reactive or tissue-specific-antibody mediated. A genetic influence should be suggested from the Japanese reports. PMID- 2198232 TI - Pharmacological interaction between tolbutamide and acetylsalicylic acid: study on insulin secretion in man. AB - This study has been planned to investigate some aspects of the interaction between acetylsalicylic acid (ASA) and tolbutamide on insulin secretion. In healthy subjects, oral administration of 3.2 g daily of ASA for 3 days significantly enhanced a) basal insulin levels (p less than 0.01), b) arginine stimulated insulin secretion (25 g i.v. over 30 min) (p less than 0.01) and c) tolbutamide-stimulated insulin secretion (1 g or 0.25 g i.v. as a bolus) (areas under curves: p less than 0.02). Corresponding decreases in glycemia were observed. Tolbutamide binding to serum proteins was significantly reduced after ASA treatment (p less than 0.02). We conclude that, in case of tolbutamide test, interferences between ASA and tolbutamide on insulin secretion might be dependent, at least in part, on enhancement of free-tolbutamide percentage in plasma and not only on a direct or synergic action of ASA on pancreatic B-cell. Therefore, acute stimulation of insulin secretion by tolbutamide appears not to be completely comparable to other traditional stimuli, when ASA effects are studied. PMID- 2198233 TI - Controlled clinical trial of propranolol alone and in combination with dilazep in patients with angina pectoris. AB - The present study was performed to see if the combined treatment with propranolol and dilazep offers any advantage over monotherapy with propranolol alone in angina of effort. Thirty-four patients out of 40 with classical stable angina of effort completed this double-blind, randomized, parallel design comparative clinical trial. Both propranolol alone (20-80 mg) and in combination with dilazep (50 mg) three times a day produced a significant reduction in anginal attacks, consumption of nitroglycerin tablets and increased exercise tolerance. Propranolol in combination with dilazep produced more reduction in these parameters as compared to when it was given alone. However, this difference was not significant. The combination of the two drugs produced a significant reduction in supine systolic blood pressure and in rate-pressure product. Laboratory data did not reveal any dysfunction of liver, kidneys and hemopoietic system. The results obtained support the anticipated additional benefit from combined therapy with propranolol and dilazep in terms of some increase in efficacy. PMID- 2198234 TI - Heterogeneity in the familial aggregation of fasting plasma glucose in five North American populations: the Lipid Research Clinics Family Study. AB - Heterogeneity in the familial aggregation of plasma glucose in five samples of the Lipid Research Clinics Family Study (LRC) was investigated using path analysis. This study was deemed appropriate since recent investigations reported a wide range of estimates for genetic and cultural factors. The path model incorporated a measured index of the familial environment in order to separate the effects of genes and environments in the nuclear family design, genetic and environmental heritabilities, spouse resemblance, sibling environmental effects, and parental cultural transmission. The methodology was completely general in allowing sample-specific, as well as pooled-sample, estimation of all or any subset of the model parameters. Genetic heritability estimates were heterogeneous, ranging from zero to 33% across the clinics. Environmental heritability (7%), spouse resemblance, non-transmitted sibling environmental effects, and parental cultural transmission were homogeneous across samples. No support was found for specific maternal effects, nor for intergenerational differences in cultural or genetic heritability. We conclude that the genetic and environmental heritabilities for plasma glucose in the LRC are consistent with the diverse reports by earlier investigators. In addition, we were able to exclude methodological differences as a cause of this heterogeneity. Furthermore, formal hypothesis tests suggest that the aetiology of this heterogeneity is genetic (and not cultural), taking the form of two distinct homogeneous patterns (one for no genetic effect, and one for a moderate genetic effect). Only formal heterogeneity tests of the type described here can detect these effects, and allow pooling of separate studies in order to obtain more precise estimates of the parameters of interest. PMID- 2198235 TI - Twenty-year stroke mortality and prediction in twelve cohorts of the Seven Countries Study. AB - Twelve cohorts of men aged 40-59 for a total of 8287 individuals in six countries (Finland, the Netherlands, Italy, Yugoslavia, Greece and Japan) were examined in the late 1950s or early 1960s for the measurement of some risk factors and then followed up for mortality and causes of death through 20 years. Large differences in 20-year death rates from stroke were recorded among cohorts, with the highest levels in the pool of the Yugoslavia (67 per 1000) and Japanese cohorts (62 per 1000) and the lowest in the Dutch cohort (22 per 1000). The simple linear correlation (among cohorts) of stroke mortality on mean levels at entry of some factors showed inverse significant coefficients for systolic (-0.63) diastolic ( 0.51) and mean blood pressure (-0.72), and for serum cholesterol (-0.72), whereas no significant coefficients were found for mean body mass index, mean cigarette consumption and mean physical activity. The Cox model solved for six national pools of cohorts showed that only age and mean blood pressure carry significant positive coefficients, whereas all the other available factors (cigarette consumption, serum cholesterol, body mass index, physical activity) did not approach significant levels except the negative coefficients of smoking habits in Greece. PMID- 2198236 TI - Repetitive BOP coupling (REBOP) in solid phase peptide synthesis. Luliberin synthesis as model. AB - The coupling reagent (benzotriazol-1-yloxy)tris-(dimethylamino)phosphonium (BOP) hexafluorophosphate was tested in the synthesis of luliberin (LH-RH) with inexpensive classically protected Boc-amino acids, in slight excess, and benzhydryl amino resin, without any other additive. The good solubility of this reagent and its by-products is of particular interest for automated peptide synthesis. [D-His2]LH-RH was also synthesized and compared with LH-RH by proton nuclear magnetic resonance spectroscopy. As shown by the biological tests and the high performance liquid chromatography study, unprotected pyroGlu and Boc-His can be used without any significant racemization but Boc-His(Boc) was found to be preferable since it gave no detectable racemization and no by-products. The difficult isolation of the minority D-derivative from the crude preparation of LH RH was resolved by a recycling procedure in reversed phase HPLC. PMID- 2198237 TI - [Importation of important infectious diseases and consequences for preventive immunization before foreign travel]. PMID- 2198238 TI - [Prevention of malaria]. PMID- 2198239 TI - [Intestinal protozoa--new aspects]. PMID- 2198240 TI - [Skin changes in patients returning from the tropics]. PMID- 2198241 TI - [Poisoning caused by maritime poisonous animals]. PMID- 2198242 TI - [Studies on tropical fitness and return from the tropics]. PMID- 2198243 TI - Medicare and the nurse. The 1980s in review. PMID- 2198244 TI - Pharmacologic manipulation of the respiratory control center in the infant. AB - The respiratory control center receives afferent stimuli from mechanical and neuromechanical sources. Information from both these sources, combined with voluntary and involuntary CNS control, effects stimulation of the respiratory muscles. In the infant, insufficiency of one or more of these elements of the respiratory control center is associated with considerable morbidity and mortality. Pharmacologic manipulation may provide a means of intervention. The xanthine derivative theophylline has been successfully used in the treatment of bronchopulmonary dysplasia and apnea in the infant. Naloxone, an endorphin antagonist, is widely used for the reversal of narcotic-induced respiratory depression but has not been shown to be clinically effective for either severely or moderately asphyxiated infants. Although doxapram has not been extensively studied and lacks an oral preparation, it is a potentially viable therapy in the treatment of refractory apnea and congenital hypoventilation syndromes. Almitrine's success in adults with chronic obstructive pulmonary disease has not been duplicated in infants with similar respiratory impairments. Progesterone and prostaglandin, although proved to influence respiratory activity, should be regarded as very experimental therapeutic modalities. PMID- 2198245 TI - Evaluation of protein digestibility-corrected amino acid score method for assessing protein quality of foods. AB - The current concepts of protein quality evaluation were reviewed. A detailed examination of existing animal assays and more promising amino acid scoring methods has been carried out by an Ad Hoc Working Group on Protein Quality Measurement for the Codex Committee on Vegetable Proteins during the last 5 years. Several factors such as inadequacies of protein efficiency ratio (PER, the poorest test) and other animal assays, advancements made in standardizing methods for amino acid analysis and protein digestibility, availability of data on digestibility of protein and individual amino acids in a variety of foods, and reliability of human amino acid requirements and scoring patterns were evaluated. On the basis of this evaluation, amino acid score, corrected for true digestibility of protein, was recommended to be the most suitable routine method for predicting protein quality of foods for humans. Amino acid scores corrected for true digestibility of protein (as determined by rat balance method) were termed "protein digestibility-corrected amino acid scores." A detailed method for the determination of the protein digestibility-corrected amino acid score was proposed, and information about the range of scores to be expected in foods or food products was provided in the present investigation. The protein digestibility-corrected amino acid score method is a simple and scientifically sound approach for routine evaluation of protein quality of foods. Accuracy of the method would, however, be confirmed after validation with growth or metabolic balance studies in humans. PMID- 2198246 TI - Genome rearrangement and genetic instability in Streptomyces spp. PMID- 2198247 TI - Regulation of NAD metabolism in Salmonella typhimurium: molecular sequence analysis of the bifunctional nadR regulator and the nadA-pnuC operon. AB - In Salmonella typhimurium, de novo synthesis of NAD is regulated through the transcriptional control of the nadA and nadB loci. Likewise, the pyridine nucleotide salvage pathway is controlled at pncB. The transcriptional expression of these three loci is coordinately regulated by the product of nadR. However, there is genetic evidence suggesting that NadR is bifunctional, serving in both regulatory and transport capacities. One class of mutations in the nadR locus imparts a transport-defective PnuA- phenotype. These mutants retain regulation properties but are unable to transport nicotinamide mononucleotide (NMN) intact across the cell membrane. Other nadR mutants lose both regulatory and transport capabilities, while a third class loses only regulatory ability. The unusual NMN transport activity requires both the PnuC and NadR proteins, with the pnuC locus residing in an operon with nadA. To prove that nadR encoded a single protein and to gain insight into a regulatory target locus, the nadR and nadA pnuC loci were cloned and sequenced. A DNA fragment which complemented both regulatory and transport mutations was found to contain a single open reading frame capable of encoding a 409-amino-acid protein (47,022 daltons), indicating that NadR is indeed bifunctional. Confirmation of the operon arrangement for nadA and pnuC was obtained through the sequence analysis of a 2.4-kilobase DNA fragment which complemented both NadA and PnuC mutant phenotypes. The nadA product, confirmed in maxicells, was a 365-amino-acid protein (40,759 daltons), while pnuC encoded a 322-amino-acid protein (36,930 daltons). The extremely hydrophobic (71%) nature of the PnuC protein indicated that it was an integral membrane protein, consistent with its central role in the transport of NMN across the cytoplasmic membrane. The results presented here and in previous studies suggest a hypothetical model in which NadR interacts with PnuC at low internal NAD levels, permitting transport of NMN intact into the cell. As NAD levels increase within the cell, the affinity of NadR for the operator regions of nadA, nadB, and pncB increases, repressing the transcription of these target genes. PMID- 2198248 TI - A gene required for very short patch repair in Escherichia coli is adjacent to the DNA cytosine methylase gene. AB - Deamination of 5-methylcytosine in DNA results in T/G mismatches. If unrepaired, these mismatches can lead to C-to-T transition mutations. The very short patch (VSP) repair process in Escherichia coli counteracts the mutagenic process by repairing the mismatches in favor of the G-containing strand. Previously we have shown that a plasmid containing an 11-kilobase fragment from the E. coli chromosome can complement a chromosomal mutation defective in both cytosine methylation and VSP repair. We have now mapped the regions essential for the two phenotypes. In the process, we have constructed plasmids that complement the chromosomal mutation for methylation, but not for repair, and vice versa. The genes responsible for these phenotypes have been identified by DNA sequence analysis. The gene essential for cytosine methylation, dcm, is predicted to code for a 473-amino-acid protein and is not required for VSP repair. It is similar to other DNA cytosine methylases and shares extensive sequence similarity with its isoschizomer, EcoRII methylase. The segment of DNA essential for VSP repair contains a gene that should code for a 156-amino-acid protein. This gene, named vsr, is not essential for DNA methylation. Remarkably, the 5' end of this gene appears to overlap the 3' end of dcm. The two genes appear to be transcribed from a common promoter but are in different translational registers. This gene arrangement may assure that Vsr is produced along with Dcm and may minimize the mutagenic effects of cytosine methylation. PMID- 2198249 TI - Cloning, sequencing, and expression of a xylanase gene from the anaerobic ruminal bacterium Butyrivibrio fibrisolvens. AB - A gene coding for xylanase activity, xynA, from the anaerobic ruminal bacterium Butyrivibrio fibrisolvens 49 was cloned into Escherichia coli JM83 by using plasmid pUC19. The gene was located on a 2.3-kilobase (kb) DNA insert composed of two adjacent EcoRI fragments of 1.65 and 0.65 kb. Expression of xylanase activity required parts of both EcoRI segments. In E. coli, the cloned xylanase enzyme was not secreted and remained cell associated. The enzyme exhibited no arabinosidase, cellulase, alpha-glucosidase, or xylosidase activity. The isoelectric point of the cloned protein was approximately 9.8, and optimal xylanase activity was obtained at pH 5.4. The nucleotide sequence of the 1,535-base-pair EcoRV-EcoRI segment from the B. fibrisolvens chromosome that included the xynA gene was determined. An open reading frame was found that encoded a 411-amino-acid-residue polypeptide of 46,664 daltons. A putative ribosome-binding site, promoter, and leader sequence were identified. Comparison of the XynA protein sequence with that of the XynA protein from alkalophilic Bacillus sp. strain C-125 revealed considerable homology, with 37% identical residues or conservative changes. The presence of the cloned xylanase gene in other strains of Butyrivibrio was examined by Southern hybridization. The cloned xylanase gene hybridized strongly to chromosomal sequences in only two of five closely related strains. PMID- 2198250 TI - Characterization of the F-plasmid conjugative transfer gene traU. AB - We characterized the traU gene of the Escherichia coli K-12 conjugative plasmid F. Plasmids carrying segments of the F transfer operon were tested for their capacity to complement F lac traU526. The protein products of TraU+ clones were identified, and the nucleotide sequence of traU was determined. traU mapped between traW and trbC. It encodes a 330-amino-acid, Mr36,786 polypeptide that is processed. Ethanol caused accumulation of a precursor polypeptide; removal of ethanol permitted processing of the protein to occur. Because F lac traU526 strains appear to be resistant to F-pilus-specific phages, traU has been considered an F-pilus assembly gene. However, electron microscopic analysis indicated that the traU526 amber mutation caused only a 50% reduction in F piliation. Since F lac traU526 strains also retain considerable transfer proficiency, new traU mutations were constructed by replacing a segment of traU with a kanamycin resistance gene. Introduction of these mutations into a transfer proficient plasmid caused a drastic reduction in transfer proficiency, but pilus filaments remained visible at approximately 20% of the wild-type frequency. Like traU526 strains, such mutants were unable to plaque F-pilus-specific phages but exhibited a slight sensitivity on spot tests. Complementation with a TraU+ plasmid restored the wild-type transfer and phage sensitivity phenotypes. Thus, an intact traU product appears to be more essential to conjugal DNA transfer than to assembly of pilus filaments. PMID- 2198251 TI - Subunit structure, expression, and function of NAD(H)-specific isocitrate dehydrogenase in Saccharomyces cerevisiae. AB - Mitochondrial NAD(H)-specific isocitrate dehydrogenase was purified from Saccharomyces cerevisiae for analyses of subunit structure and expression. Two subunits of the enzyme with different molecular weights (39,000 and 40,000) and slightly different isoelectric points were resolved by denaturing electrophoretic techniques. Sequence analysis of the purified subunits showed that the polypeptides have different amino termini. By using an antiserum to the native enzyme prepared in rabbits, subunit-specific immunoglobulin G fractions were obtained by affinity purification, indicating that the subunits are also immunochemically distinct. The levels of NAD(H)-specific isocitrate dehydrogenase activity and immunoreactivity were found to correlate closely with those of a second tricarboxylic acid cycle enzyme, malate dehydrogenase, in yeast cells grown under a variety of conditions. S. cerevisiae mutants with defects in NAD(H) specific isocitrate dehydrogenase were identified by screening a collection of yeast mutants with acetate-negative growth phenotypes. Immunochemical assays were used to demonstrate that one mutant strain lacks the 40,000-molecular-weight subunit (IDH1) and that a second strain lacks the 39,000-molecular-weight subunit (IDH2). Mitochondria isolated from the IDH1 and IDH2 mutants exhibited a markedly reduced capacity for utilization of either isocitrate or citrate for respiratory O2 consumption. This confirms an essential role for NAD(H)-specific isocitrate dehydrogenase in oxidative functions in the tricarboxylic acid cycle. PMID- 2198252 TI - Cloning of aldB, which encodes alpha-acetolactate decarboxylase, an exoenzyme from Bacillus brevis. AB - A gene for alpha-acetolactate decarboxylase (ALDC) was cloned from Bacillus brevis in Escherichia coli and in Bacillus subtilis. The 1.3-kilobase-pair nucleotide sequence of the gene, aldB, encoding ALDC and its flanking regions was determined. An open reading frame of 285 amino acids included a typical N terminal signal peptide of 24 or 27 amino acids. A B. subtilis strain harboring the aldB gene on a recombinant plasmid processed and secreted ALDC. In contrast, a similar enzyme from Enterobacter aerogenes is intracellular. PMID- 2198253 TI - Differentiation of Serratia marcescens 274 into swimmer and swarmer cells. AB - We describe a new sensory response in the enteric bacterium Serratia marcescens. When grown in liquid media, the bacteria were short rods with one to two flagella and displayed classical swimming behavior. Upon transfer to a solid surface (0.7 to 0.8T% agar medium), the bacteria underwent a dramatic change of form. They ceased septation, elongated, and expressed numerous (10 to 100) flagella that covered the lateral sides of the cells. The bacteria now displayed a different form of locomotion--swarming--which allowed them to rapidly move over the top of the solid surface. The differentiation to either swimmer or swarmer cells could be reversed by growth on solid or liquid medium, respectively. To identify conditions that influence this differentiation, the growth environment of S. marcescens was manipulated extensively. The swarming response was monitored by visual and microscopic observation of cell movement on solid surfaces, by immunofluorescent labeling followed by microscopic observation for the presence of elongated, profusely flagellated cells, as well as by estimation of induction of flagellin protein, using Western immunoblot analysis. Conditions that imposed a physical constraint on bacterial movement, such as solid or viscous media, were the most efficient at inducing the swarming response. No chemical constituent of the medium that might contribute to the response could be identified, although the existence of such a component cannot be ruled out. Both swimmer and swarmer cells had flagellin proteins of identical molecular weight, which produced similar proteolysis patterns upon digestion with trypsin. PMID- 2198254 TI - Thermotolerance is independent of induction of the full spectrum of heat shock proteins and of cell cycle blockage in the yeast Saccharomyces cerevisiae. AB - Cells of the yeast Saccharomyces cerevisiae are known to acquire thermotolerance in response to the stresses of starvation or heat shock. We show here through the use of cell cycle inhibitors that blockage of yeast cells in the G1, S, or G2 phases of the mitotic cell cycle is not a stress that induces thermotolerance; arrested cells remained as sensitive to thermal killing as proliferating cells. These G1- or S-phase-arrested cells were unimpaired in the acquisition of thermotolerance when subjected to a mild heat shock by incubation at 37 degrees C. One cell cycle inhibitor, o-phenanthroline, did in fact cause cells to become thermotolerant but without induction of the characteristic pattern of heat shock proteins. Thermal induction of heat shock protein synthesis was unaffected; the o phenanthroline-treated cells could still synthesize heat shock proteins upon transfer to 37 degrees C. Use of a novel mutant conditionally defective only for the resumption of proliferation from stationary phase (M. A. Drebot, G. C. Johnston, and R. A. Singer, Proc. Natl. Acad. Sci. USA 84:7948-7952, 1987) indicated that o-phenanthroline inhibition produces a stationary-phase arrest, a finding which is consistent with the increased thermotolerance and regulated cessation of proliferation exhibited by the inhibited cells. These findings show that the acquired thermotolerance of cells is unrelated to blockage of the mitotic cell cycle or to the rapid synthesis of the characteristic spectrum of heat shock proteins. PMID- 2198255 TI - Genetic and behavioral analysis of flagellar switch mutants of Salmonella typhimurium. AB - At the interface between the sensory transduction system and the flagellar motor system of Salmonella typhimurium, the switch complex plays an important role in both sensory transduction and energy transduction. To examine the function of the switch complex, we isolated from 10 cheY mutants 500 pseudorevertants with a suppressor mutation in one of the three genes (fliG, fliM, and fliN) encoding the switch complex. Detailed mapping revealed that these suppressor mutations were localized to several segments of each switch gene, suggesting localization of functional sites on the switch complex. These switch mutations were introduced into the wild-type background and into a chemotaxis deletion background. Behavior of the pseudorevertants and their derivatives (1,500 strains in all) was observed by light microscopy. In the chemotaxis deletion background, about 70% of the switch mutants showed smooth swimming and the rest showed more or less tumbly swimming. There was some correlation between the mutational sites and the swimming patterns in the chemotaxis deletion background, suggesting that there is segregation of functional sites on the switch complex. The interaction of the switch complex with the chemotaxis protein, CheY, and the stochastic nature of switching in the absence of CheY are discussed. PMID- 2198256 TI - Molecular cloning and physical and functional characterization of the Salmonella typhimurium and Salmonella typhi galactose utilization operons. AB - The chromosomally encoded galactose utilization (gal) operons of Salmonella typhimurium and S. typhi were each cloned on similar 5.5-kilobase HindIII fragments into pBR322 and were identified by complementation of Gal- Escherichia coli strains. Restriction endonuclease analyses indicated that these Salmonellae operons share considerable homology, but some heterogeneities in restriction sites were observed. Subcloning and exonuclease mapping experiments showed that both operons have the same genetic organization as that established for the E. coli gal operon (i.e., 5' end, promoter, epimerase, transferase, kinase, and 3' end). Two gal operator regions (oE and oI) of S. typhimurium, identified by repressor titration in an E. coli superrepressor [galR(Sup)] mutant, were sequenced and found to flank the promoter region. This promoter region is identical to the -10 and -35 regions of the E. coli gal operon. Minicell studies demonstrated that the three gal structural genes of S. typhimurium encode separate polypeptides of 39 kilodaltons (kDa) (epimerase, 337 amino acids [aa's]), 41 kDa (transferase, 348 aa's), and 43 kDa (kinase, 380 aa's). Despite functional and organizational similarities, DNA sequence analysis revealed that the S. typhimurium gal genes show less than 70% homology to the E. coli gal operon. Because of codon degeneracy, the deduced amino acid sequences of these polypeptides are highly conserved (greater than 90% homology) as compared with those of the E. coli gal enzymes. These studies have defined basic genetic parameters of the gal genes of two medically important Salmonella species, and our findings support the hypothesized divergent evolution of E. coli and Salmonella spp. from a common ancestral parent bacterium. PMID- 2198258 TI - Phospholipid biosynthesis in Candida albicans: regulation by the precursors inositol and choline. AB - Phospholipid metabolism in the pathogenic fungus Candida albicans was examined. The phospholipid biosynthetic pathways of C. albicans were elucidated and were shown to be similar to those of Saccharomyces cerevisiae. However, marked differences were seen between these two fungi in the regulation of the pathways in response to exogenously provided precursors inositol and choline. In S. cerevisiae, the biosynthesis of phosphatidylcholine via methylation of phosphatidylethanolamine appears to be regulated in response to inositol and choline; provision of choline alone does not repress the activity of this pathway (G. M. Carman and S. A. Henry, Annu. Rev. Biochem. 58:636-669, 1989). The same pathway in C. albicans responds to the exogenous provision of choline. Possible explanations for the observed differences in regulation are discussed. PMID- 2198257 TI - Complementation of Escherichia coli sigma 54 (NtrA)-dependent formate hydrogenlyase activity by a cloned Thiobacillus ferrooxidans ntrA gene. AB - The ntrA gene of Thiobacillus ferrooxidans was cloned by complementation of an Escherichia coli ntrA mutant that was unable to produce gas via the sigma 54 (NtrA)-dependent formate hydrogenlyase pathway. Analysis of the DNA sequence showed that the T. ferrooxidans ntrA gene coded for a protein of 475 amino acids (calculated Mr, 52,972). The T. ferrooxidans NtrA protein had 49, 44, 33, and 18% amino acid similarity with the NtrA proteins of Klebsiella pneumoniae, Azotobacter vinelandii, Rhizobium meliloti, and Rhodobacter capsulatus, respectively. The ability of the T. ferrooxidans NtrA protein to direct transcription from sigma 54-dependent promoters was demonstrated in E. coli by using fdhF-lacZ and nifH-lacZ fusions. An open reading frame coding for a protein of 241 amino acids (calculated Mr, 27,023) was situated 12 base pairs upstream of the T. ferrooxidans ntrA gene. Comparison of this protein with the product of the open reading frame ORF1, located upstream of the R. meliloti ntrA gene, showed that the two proteins had 55% amino acid similarity. The cloned T. ferrooxidans ntrA gene was expressed in E. coli from a promoter located within the ORF1 coding region. PMID- 2198259 TI - Location of a P1 plasmid replication inhibitor determinant within the initiator gene. AB - The P1 plasmid replication initiator protein, RepA, binds to its own promoter and represses transcription efficiently. There are only about 20 RepA dimers present per repA gene. A possible reason for this highly restrained expression became evident when repA expression was increased by using foreign promoters: with fivefold overexpression, the replication rate was diminished, and with 40-fold overexpression, replication was not detectable. The inhibition was P1 specific: growth of Escherichia coli and replication of pSC101, R6K, and mini-F plasmids were not affected. The activity is apparently not from RepA itself. Excess purified RepA did not inhibit replication in vitro. Mutations of the repA translation initiation codon reduced synthesis of the initiator but not the inhibitory activity. Deletion from either the N- or C-terminal ends of repA (28 and 69 codons, respectively, out of the 286-codon open reading frame) affected the initiator but not the inhibitory activity. Further deletions affected both the activities. These results demonstrate that the integrity of the initiator is not required for inhibition, but involvement of an unstable initiator fragment or of initiator mRNA cannot be ruled out. PMID- 2198260 TI - Cloning and expression of the ponB gene, encoding penicillin-binding protein 1B of Escherichia coli, in heterologous systems. AB - A fragment from the ponB region of the Escherichia coli chromosome comprising the promoterless sequence encoding penicillin-binding protein 1B (PBP 1B) has been cloned in a broad-host-range expression vector under the control of the kanamycin resistance gene promoter present in the vector. The hybrid plasmid (pJP3) was used to transform appropriate strains of Salmonella typhimurium, Pseudomonas putida, and Pseudomonas aeruginosa. In all instances, the coding sequence was expressed in the heterologous hosts, yielding a product with electrophoretic mobility, protease accessibility, membrane location, and beta-lactam-binding properties identical to those of native PBP 1B in E. coli. These results indicated that PBP 1B of E. coli is compatible with the cytoplasmic membrane environment of unrelated bacterial species and support the idea that interspecific transfer of mutated alleles of genes coding for PBPs could potentially be an efficient spreading mechanism for intrinsic resistance to beta lactams. PMID- 2198261 TI - Genetic evidence that NarL function is not required for nitrate regulation of nitrate assimilation in Klebsiella pneumoniae M5al. AB - We cloned the narL gene, required for nitrate induction of respiratory nitrate reductase synthesis, from Klebsiella pneumoniae. The E. coli narL gene product shares sequence similarity with the response regulator proteins of two-component regulatory systems. We found that narL(+)-containing plasmids restored nitrate regulation of anaerobic respiratory gene expression in appropriate Escherichia coli hosts. The K. pneumoniae narL region encoded a protein whose migration in Laemmli gels was indistinguishable from that of the narL product of E. coli. We constructed a narL::Km mutant of K. pneumoniae. This mutation abolished nitrate induction of respiratory nitrate reductase synthesis but had no effect on nitrate induction of assimilatory nitrate and nitrite reductase synthesis. We conclude that K. pneumoniae has distinct nitrate-responsive regulators for controlling respiratory and assimilatory gene expression. PMID- 2198262 TI - Rhizobitoxine inhibition of hydrogenase synthesis in free-living Bradyrhizobium japonicum. AB - Rhizobitoxine produced by Bradyrhizobium species strongly prevented derepression of hydrogenase expression in free-living Bradyrhizobium japonicum, although the toxin had no effect on the activity of cells which had already synthesized hydrogenase protein. Dihydrorhizobitoxine, a structural analog of rhizobitoxine, proved to be a less potent inhibitor of hydrogenase derepression. Rhizobitoxine did not cause cell death at a concentration sufficient to eliminate hydrogenase expression. The large subunit of hydrogenase was not detectable with antibody after derepression in the presence of rhizobitoxine. The general pattern of proteins synthesized from 14C-labeled amino acids during derepression was not significantly different in the presence or absence of rhizobitoxine. These results indicated that rhizobitoxine inhibited hydrogenase synthesis in free living B. japonicum. Cystathionine and methionine strongly prevented the inhibition of hydrogenase derepression by rhizobitoxine, suggesting that the inhibition involves the level of sulfur-containing amino acids in the cell. PMID- 2198263 TI - Cloning and characterization of Kluyveromyces lactis SEC14, a gene whose product stimulates Golgi secretory function in Saccharomyces cerevisiae. AB - The Saccharomyces cerevisiae SEC14 gene encodes a cytosolic factor that is required for secretory protein movement from the Golgi complex. That some conservation of SEC14p function may exist was initially suggested by experiments that revealed immunoreactive polypeptides in cell extracts of the divergent yeasts Kluyveromyces lactis and Schizosaccharomyces pombe. We have cloned and characterized the K. lactis SEC14 gene (SEC14KL). Immunoprecipitation experiments indicated that SEC14KL encoded the K. lactis structural homolog of SEC14p. In agreement with those results, nucleotide sequence analysis of SEC14KL revealed a gene product of 301 residues (Mr, 34,615) and 77% identity to SEC14p. Moreover, a single ectopic copy of SEC14KL was sufficient to render S. cerevisiae sec14-1(Ts) mutants, or otherwise inviable sec14-129::HIS3 mutant strains, completely proficient for secretory pathway function by the criteria of growth, invertase secretion, and kinetics of vacuolar protein localization. This efficient complementation of sec14-129::HIS3 was observed to occur when the rates of SEC14pKL and SEC14p synthesis were reduced by a factor of 7 to 10 with respect to the wild-type rate of SEC14p synthesis. Taken together, these data provide evidence that the high level of structural conservation between SEC14p and SEC14pKL reflects a functional identity between these polypeptides as well. On the basis of the SEC14p and SEC14pKL primary sequence homology to the human retinaldehyde-binding protein, we suggest that the general function of these SEC14p species may be to regulate the delivery of a hydrophobic ligand to Golgi membranes so that biosynthetic secretory traffic can be supported. PMID- 2198264 TI - Nucleotide sequence of the streptococcal pyrogenic exotoxin type B gene and relationship between the toxin and the streptococcal proteinase precursor. AB - The streptococcal pyrogenic exotoxin (SPE) type B-encoding structural gene, speB, was subcloned from a 4.5-kilobase streptococcal DNA insert onto a 2.4-kilobase insert, which was then sequenced. Studies indicated that a 1,194-base-pair open reading frame encoded a 398-amino-acid protein. Removal of the putative signal peptide resulted in a mature protein with 371 residues (molecular weight, 40,314), which was subsequently proteolyzed to yield a 253-residue breakdown product (molecular weight, 27,588). This processing was confirmed by amino terminal sequencing of both the 40,314-molecular-weight protein and the breakdown product. Monte Carlo analysis indicated that SPE B was relatively dissimilar to other members of the pyrogenic toxin family that also includes SPEs A and C, toxic shock syndrome toxin 1, and the staphylococcal enterotoxins. Comparison with the published amino acid sequence of streptococcal proteinase precursor as well as DNA hybridization experiments indicated that SPE B is a variant of this protein even though the particular gene sequenced did not encode a proteolytically active molecule. PMID- 2198265 TI - Plus-origin mapping of single-stranded DNA plasmid pE194 and nick site homologies with other plasmids. AB - Staphylococcus aureus plasmid pE194 manifests a natural thermosensitivity for replication and can be established in several species, both gram positive and gram negative, thus making it attractive for use as a delivery vector. Like most characterized plasmids of gram-positive bacteria, pE194 generates single-stranded DNA. The direction of pE194 replication is clockwise, as determined by the strandedness of free single-stranded DNA. Significant homology exists between a 50-base-pair sequence in the origin of pE194 and sequences present in plasmids pMV158 (Streptococcus agalactiae), pADB201 (Mycoplasma mycoides), and pSH71 (Lactococcus lactis). We used an initiation-termination reaction, in which pE194 initiates replication at its own origin and is induced to terminate at the related pMV158 sequence, to demonstrate that pE194 replicates by a rolling-circle mechanism; the initiation nick site was localized to an 8-base-pair sequence. PMID- 2198266 TI - Genes of the Escherichia coli pur regulon are negatively controlled by a repressor-operator interaction. AB - Fusions of lacZ were constructed to genes in each of the loci involved in de novo synthesis of IMP. The expression of each pur-lacZ fusion was determined in isogenic purR and purR+ strains. These measurements indicated 5- to 17-fold coregulation of genes purF, purHD, purC, purMN, purL, and purEK and thus confirm the existence of a pur regulon. Gene purB, which encodes an enzyme involved in synthesis of IMP and in the AMP branch of the pathway, was not regulated by purR. Each locus of the pur regulon contains a 16-base-pair conserved operator sequence that overlaps with the promoter. The purR product, purine repressor, was shown to bind specifically to each operator. Thus, binding of repressor to each operator of pur regulon genes negatively coregulates expression. PMID- 2198267 TI - Development of an integrative DNA transformation system for the yeast Candida tropicalis. AB - We developed the alkane and fatty-acid utilizing yeast Candida tropicalis as a host for DNA transformations. The system is based on an auxotrophic mutant host of C. tropicalis which is defective in orotidine monophosphate decarboxylase (ura3). The ura3 host was isolated by mutagenesis and a double-selection procedure that combined nystatin enrichment selection and 5-fluoro-orotic acid resistance selection. As a selectable marker, we isolated and characterized the C. tropicalis URA3 gene. Plasmid vectors that contained the C. tropicalis URA3 gene transformed the C. tropicalis mutant host at a frequency of 10(3) to 10(4) transformants per micrograms of plasmid DNA. Vectors that contained the Saccharomyces cerevisiae URA3 gene could not transform C. tropicalis. DNA transfer was accomplished by modified versions of either spheroplast generation (CaCl2-polyethylene glycol)-fusion or cation (LiCl) procedures developed for S. cerevisiae. Plasmid vectors that had been cut within the C. tropicalis URA3 fragment integrated by homologous recombination at the URA3 locus. PMID- 2198268 TI - Actinobacillus pleuropneumoniae hlyX gene homology with the fnr gene of Escherichia coli. AB - The hlyX gene from Actinobacillus pleuropneumoniae, which confers a hemolytic phenotype on Escherichia coli, was sequenced, and its role in regulation of gene expression was investigated. No similarity was found between the hlyX sequence and sequences of known hemolysin or cytotoxin genes. However, the hlyX sequence was very similar to that of the fnr gene of Escherichia coli which encodes the global regulatory protein, FNR. Comparison of the deduced amino acid sequence of the hlyX gene product (HlyX) with that of FNR revealed a high degree of well aligned sequence correlation throughout the polypeptide chain. For example, 23 of 24 amino acids in the DNA-binding region of FNR are identical in the corresponding region of HlyX. Four cysteine residues in the amino-terminal region are also conserved. The promoter region of hlyX is very similar to that of fnr. It has a putative -10 sequence which closely resembles the E. coli -10 consensus sequence. This sequence is overlapped by a potential operator which is very similar to the FNR-binding-site consensus sequence. Functional homology between HlyX and FNR was also demonstrated. Plasmids carrying hlyX complemented the nutritional lesion of an fnr deletion strain of E. coli. These data suggest that HlyX may regulate, rather than mediate, hemolytic activity in E. coli, but the possibility that HlyX is both a regulator of gene expression and a hemolysin cannot be excluded. PMID- 2198269 TI - Intrinsic bends and integration host factor binding at F plasmid oriT. AB - F plasmid oriT DNA extending from the F kilobase coordinate 66.7 (base pair [bp] 1 on the oriT sequence map) rightward to bp 527 was analyzed for intrinsic bends (by permutation assays) and for binding of integration host factor (IHF) (by gel retardation and DNase footprinting). Intrinsic bending of the 527-bp fragment (bend center approximately at bp 240) was represented as a composite of at least two components located near bp 170 and near bp 260. IHF bound primarily to a site extending from bp 165 to 195 and with lower affinity to a site extending from bp 287 to 319. The intrinsic curvature and sequences to which IHF binds (IHF is known to bend DNA) may play a structural role in oriT function. PMID- 2198272 TI - Isogenic variants of Escherichia coli with altered morphology have peptidoglycan with identical muropeptide composition. AB - The peptidoglycan compositions of three isogenic morphological mutants of Escherichia coli were determined by high-pressure liquid chromatography analysis. The muropeptide compositions of the peptidoglycan of these mutants were the same, indicating that the shape of E. coli is not (solely) determined by the chemical composition of the peptidoglycan. Furthermore, it appeared that the muropeptide composition of the peptidoglycan was not affected by growth temperature. PMID- 2198270 TI - Nucleotide sequence and analysis of the speA gene encoding biosynthetic arginine decarboxylase in Escherichia coli. AB - The DNA sequence of a 3.23-kilobase fragment of the Escherichia coli chromosome encoding biosynthetic arginine decarboxylase (ADC) was determined. This sequence contained the speA open reading frame (ORF) as well as partial speB and metK ORFs. The ADC ORF is 1,974 nucleotides long; the deduced polypeptide contains 658 amino acids with a molecular size of 73,980 daltons. The molecular weight and predicted ADC amino acid composition are nearly identical to the amino acid analysis of purified ADC performed by Wu and Morris (J. Biol. Chem. 248:1687 1695, 1973). A translational speA-lacZ fusion, pRM65, including 1,389 base pairs (463 amino acids) of the 5' end of speA was constructed. Western blots (immunoblots) with beta-galactosidase antisera revealed two ADC::beta galactosidase fusion proteins in E. coli bearing pRM65: 160,000 and 156,000 daltons representing precursor and mature hybrid proteins, respectively. The predicted amino acid sequence of ADC contains a region of six amino acid residues found in two bacterial diaminopimelic acid decarboxylases and three eucaryotic ornithine decarboxylases. This conserved sequence is located approximately eight amino acids from the putative pyridoxal phosphate-binding site of ADC and is predicted to be involved in substrate binding. PMID- 2198271 TI - Cloning, expression, and characterization of the Escherichia coli K-12 rfaD gene. AB - The rfaD gene encodes ADP-L-glycero-D-mannoheptose-6-epimerase, an enzyme required for the biosynthesis of the lipopolysaccharide precursor ADP-L-glycerol D-mannoheptose. The precise localization of the rfaD gene on a 1.3-kilobase SspI HpaI fragment is reported. The rfaD gene and the flanking regions were completely sequenced. The location of the rfaD gene on the physical map of the Escherichia coli chromosome was determined. Primer extension studies were used to define the regulatory region of the rfaD gene. The cloned rfaD gene directed the synthesis of a 37,000-dalton polypeptide in several in vivo and in vitro expression systems. N-terminal analysis of purified ADP-L-glycero-D-mannoheptose-6-epimerase confirmed the first 34-amino-acid sequence deduced from the nucleotide sequence of the rfaD gene coding region. The primary structure of the rfaD protein contains the sequence fingerprint for the ADP-binding beta alpha beta fold at the N terminus. PMID- 2198273 TI - Molecular cloning, nucleotide sequence, and expression of shl, a new gene in the 2-minute region of the genetic map of Escherichia coli. AB - Cells of Escherichia coli that harbor supH (an allele of the wild-type gene serU) are sensitive to UV irradiation and temperature and appear to have an impaired cell division control mechanism. We found that a gene located at the 2-min region, designated shl, inhibited the growth of supH-harboring cells when carried by a high-copy-number plasmid, whereas the same plasmid had no visible effect when present in parental cells. The amino acid sequence predicted from the nucleotide sequence of the shl gene indicated a similarity to the GalR and LacI repressor proteins, suggesting it is a transcription regulator. The sequence between the promoter and the structural genes revealed the presence of a short open reading frame of 28 amino acid residues followed by a segment of 81 base pairs. These structural features suggest that a transcription antitermination mechanism may be involved in the regulation of expression of the shl gene. The possibility that shl is a regulator of serU is discussed. PMID- 2198274 TI - High-level expression of the FtsA protein inhibits cell septation in Escherichia coli K-12. AB - DNA fragments encoding the ftsA gene were subcloned into plasmids downstream of a lac promoter or a tac promoter. These plasmid constructs, when transformed into wild-type and mutant strains, inhibited normal cell septation, causing the formation of long nonseptate filaments. This phenotype is due to overproduction of the FtsA protein. PMID- 2198276 TI - Molecular scanning methods of mutation detection. PMID- 2198275 TI - Stimulation of glutamine transport by osmotic stress in Escherichia coli K-12. AB - Osmotic stress produced by high concentrations of sucrose stimulated the high affinity transport of glutamine in Escherichia coli cells. Glutamine transport via a low-affinity system was not affected. Osmotic stress produced by NaCl, in contrast, inhibited the transport of glutamine and some other amino acids. Maltose transport was strongly inhibited by osmotic stress. PMID- 2198277 TI - Antibody exchange immunochemistry. AB - Antibodies are found to transfer rapidly between antigen samples attached to separate solid supports. The half-times for this antibody exchange at 20 and 37 degrees C were 7 and 1 h, respectively. Antibody exchange was exhibited by all 17 polyclonal and monoclonal antibodies tested and was readily detected by enzyme linked immunosorbent assay, immunoblotting, or immunocytochemical assays. Taking advantage of this phenomenon, antibodies can be affinity-purified using less than a picomole of antigen and small amounts of antibody. PMID- 2198278 TI - Identification of HPV-16 E7 peptides that are potent antagonists of E7 binding to the retinoblastoma suppressor protein. AB - Complex formation between the human papilloma virus type-16 E7 protein (HPV-16 E7) and the retinoblastoma suppressor protein (pRB) is believed to be important in the process of cellular transformation that leads to cervical carcinoma. Utilizing an in vitro solution assay as well as a plate binding assay that measures the association between HPV-16 E7 and pRB proteins, we have examined a series of synthetic HPV-16 E7 peptides. HPV-16 E7 peptides which lie between amino acid residues 14 and 32 were found to be potent inhibitors of E7/pRB binding. The minimal peptide structure that possessed full antagonist activity was N-acetyl-E7-(21-29)-peptide amide. This peptide inhibited 100% of E7/pRB binding and exhibited an IC50 of 40 nM in the plate binding assay. A purified beta-galactosidase-E7 fusion protein exhibited an IC50 of 2 nM in the same assay. These results suggest that other regions of the E7 molecule in addition to amino acids 21-29 may contributed to E7/pRB interaction. Analysis of E7-(20-29) peptides containing single amino acid substitutions suggests that Cys24, Tyr23, Tyr25, Asp21, and Glu26 are important residues for maintaining maximal antagonist activity. This series of peptides should prove useful in analyzing the biological consequences of E7/pRB binding in HPV-infected cells. PMID- 2198279 TI - Reaction of LexA repressor with diisopropyl fluorophosphate. A test of the serine protease model. AB - The LexA repressor of Escherichia coli modulates the expression of the SOS regulon. In the presence of DNA damaging agents in vivo, the 202-amino acid LexA repressor is inactivated by specific RecA-mediated cleavage of the Ala-84/Gly-85 peptide bond. In vitro. LexA cleavage requires activated RecA at neutral pH, and proceeds spontaneously at high pH in an intramolecular reaction termed autodigestion. A model has been proposed for the mechanism of autodigestion in which serine 119 serves as the reactive nucleophile that attacks the Ala-84/Gly 85 peptide bond in a manner analogous to a serine protease, while uncharged lysine 156 activates the serine 119 hydroxyl group. In this work, we have tested this model by examining the effect of the serine protease inhibitor diisopropyl fluorophosphate (DFP) on autodigestion. We found that DFP inhibited autodigestion and that serine 119 was the only serine residue to react with DFP. We also examined [3H]DFP incorporation by a number of cleavage-impaired LexA mutant proteins and found that mutations in the proposed active site, but not in the cleavage site, significantly reduced the rate of [3H]DFP incorporation. Finally, we showed that the purified carboxyl-terminal domain, which contains the proposed catalytic residues, incorporated [3H]DFP at a rate indistinguishable from the intact protein. These data further support our current model for the mechanism of autodigestion and the organization of LexA. PMID- 2198280 TI - Human monocyte colony-stimulating factor enhances the clearance of lipoproteins containing apolipoprotein B-100 via both low density lipoprotein receptor dependent and -independent pathways in rabbits. AB - To investigate the effects of recombinant human monocyte colony-stimulating factor (M-CSF) on plasma cholesterol metabolism, we injected M-CSF intravenously into New Zealand White rabbits (n = 13) at a dose of 100 micrograms/day for 7 days. After the treatment, the plasma cholesterol levels fell by 33.2% from 61.4 +/- 25.9 to 41.0 +/- 10.2 mg/dl (mean +/- S.D.). We also injected a large dose of M-CSF (500 micrograms/day) for 6 days into Watanabe Heritable Hyperlipidemic rabbits, which are deficient in low density lipoprotein (LDL) receptors. Again, there was a significant reduction in plasma cholesterol levels by 36.2% from 730.5 +/- 176.4 to 466.0 +/- 104.9 mg/dl (n = 4). In the kinetic studies in New Zealand White rabbits with very low density lipoprotein, LDL, and methylated LDL, the removal rates of those lipoproteins were increased 1.9-, 1.7-, and 2.0-fold, respectively, after the treatment. Immunoblot analysis of LDL receptors in the treated rabbits showed no significant changes in LDL receptor proteins in livers but a great increase in spleens and bone marrows compared with the controls. Messenger RNA was also estimated by Northern blotting in both groups, and the results were compatible with those from the immunoblot. The data suggest that M CSF stimulates the clearance of lipoproteins containing apolipoprotein B-100 via both LDL receptor-dependent and -independent pathways in target cells of M-CSF and reduces plasma cholesterol. PMID- 2198281 TI - Kinetic mechanism of dihydropyrimidine dehydrogenase from pig liver. AB - Data on initial velocity and isotope exchange at equilibrium suggest a nonclassical ping-pong mechanism for the dihydropyrimidine dehydrogenase from pig liver. Initial velocity patterns in the absence of inhibitors appeared parallel at low reactant concentration, with substrate inhibition by NADPH that is competitive with uracil and with substrate inhibition by uracil that is uncompetitive with NADPH. The Km values for both uracil (1 microM) and NADPH (7 microM) are low. As a result, it was difficult to determine whether the initial velocity pattern in the absence of added inhibitors was parallel. Thus, the pattern was redetermined in the presence of the dead-end inhibitor 2,6 dihydroxypyridine, which binds to both sites. This treatment effectively eliminates the inhibition by both substrates and increases their Km values, giving a strictly parallel pattern. Product and dead-end inhibition patterns are consistent with a mechanism in which NADPH reduces the enzyme at site 1 and electrons are transferred to site 2 to reduce uracil to dihydrouracil. The predicted mechanism is corroborated by exchange between [14C] NADP and NADPH as well as [14C]thymine and dihydrothymine in the absence of the other substrate product pair. PMID- 2198282 TI - Identification of key residues in the amino-terminal third of human interleukin-1 alpha. AB - Two mutational approaches were used to perform a thorough structure-function analysis of the first 53 residues of the 159-residue cytokine human interleukin-1 alpha (hIL-1 alpha). In this study, a total of 26 deletions, 97 multiple amino acid substitutions, and 46 single amino acid substitutions were examined. A synthetic hIL-1 alpha gene with many unique restriction sites was constructed to facilitate the molecular manipulations that were performed. The mutational methods employed include: Bal-31 exonuclease-generated deletions at unique restriction sites and combinatorial cassette mutagenesis via segment replacement with synthetic DNA. The mutant hIL-1 alpha proteins were expressed at high levels in Escherichia coli and were assayed for biological activity in a mouse T cell proliferation assay. We observed that the activity of hIL-1 alpha was extraordinarily sensitive to deletion mutations. Most internal deletions of as few as 1 or 2 residues substantially reduced biological activity. Combinatorial cassette mutagenesis on residues 13-53 of hIL-1 alpha identified 15 important residue positions. Of these, 8 displayed strong preferences for residues with hydrophilic side chains, and the remainder preferred hydrophobic side chains. We found that functional hIL-1 alpha had an absolute requirement for a basic residue (Arg, Lys, or His) at either position 15 or 16, and that Leu was preferred at position 40. PMID- 2198283 TI - Baculovirus-directed expression of the human insulin receptor and an insulin binding ectodomain. AB - In this report we describe the use of the baculovirus expression system to overproduce the human insulin holoreceptor (HIR) and a truncated, secretory version of the HIR cDNA (HIRsec) consisting of the alpha subunit and the extracellular portion of the beta subunit (beta'). Sf9 cells infected with the full-length HIR viruses synthesize recombinant HIR (rHIR) with an insulin-binding alpha subunit of apparent Mr = 110,000 and a beta subunit of apparent Mr = 80,000. Uncleaved alpha beta proreceptor accumulates in infected cells. Both of these forms assemble into higher order disulfide-linked dimers or heterotetramers of apparent Mr greater than 350,000. Insulin-binding activity in cells infected with rHIR viruses is present predominantly on the extracellular aspect of the plasma membrane (greater than 80%). Insulin binding to the full-length rHIR occurs with typical complex kinetics with Kd1 = 0.5-1 x 10(-9) M and Kd2 = 10(-7) M and receptors are present in large amounts in infected cells (1 x 10(6) receptors/cell; 1-2 mg HIR/10(9) cells). The full-length rHIR undergoes insulin dependent autophosphorylation; half-maximal activation of beta subunit autophosphorylation occurs at 1-2 x 10(-8) M. The alpha beta proreceptor also becomes phosphorylated in vitro. Analysis of tryptic phosphopeptides derived from in vitro autophosphorylated beta subunit and alpha beta proreceptor reveals a pattern of phosphorylation that is indistinguishable from that of authentic placental HIR. Sf9 cells infected with rHIRsec viruses synthesize and secrete an (alpha beta')2 heterotetrameric complex having an insulin-binding alpha subunit of apparent Mr = 110,000 and a truncated beta' subunit of apparent Mr = 45,000 that lacks kinase activity. The rHIRsec complex purified from the conditioned medium of infected cells binds insulin with high affinity (Kd = 10(-9) M). PMID- 2198284 TI - Biosynthesis and turnover of O-acetyl and N-acetyl groups in the gangliosides of human melanoma cells. AB - We and others previously described the melanoma-associated oncofetal glycosphingolipid antigen 9-O-acetyl-GD3, a disialoganglioside O-acetylated at the 9-position of the outer sialic acid residue. We have now developed methods to examine the biosynthesis and turnover of disialogangliosides in cultured melanoma cells and in Golgi-enriched vesicles from these cells. O-Acetylation was selectively expressed on di- and trisialogangliosides, but not on monosialogangliosides, nor on glycoprotein-bound sialic acids. Double-labeling of cells with [3H]acetate and [14C]glucosamine introduced easily detectable labels into each of the components of the ganglioside molecules. Pulse-chase studies of such doubly labeled molecules indicated that the O-acetyl groups turn over faster than the parent molecule. When Golgi-enriched vesicles from these cells were incubated with [acetyl-3H]acetyl-coenzyme A, the major labeled products were disialogangliosides. [Acetyl-3H]O-acetyl groups were found at both the 7- and the 9-positions, indicating that both 7-O-acetyl GD3 and 9-O-acetyl GD3 were synthesized by the action of O-acetyltransferase(s) on endogenous GD3. Analysis of the metabolically labeled molecules confirmed the existence of both 7- and 9-O acetylated GD3 in the intact cells. Surprisingly, the major 3H-labeled product of the in vitro labeling reaction was not O-acetyl-GD3, but GD3, with the label exclusively in the sialic acid residues. Fragmentation of the labeled sialic acids by enzymatic and chemical methods showed that the 3H-label was exclusively in [3H]N-acetyl groups. Analyses of the double-labeled sialic acids from intact cells also showed that the 3H-label from [3H]acetate was exclusively in the form of [3H]N-acetyl groups, whereas the 14C-label was at the 4-position. Pulse-chase analysis of the 3H/14C ratio showed that the N-acetyl groups of both GD3 and of the monosialoganglioside GM3 were turning over faster than the parent molecules. Selective periodate oxidation showed that both the inner and outer sialic acid residues of GD3 incorporated 3H-label in the in vitro reaction, and showed similar turnover of N-acetylation in the pulse-chase study. Taken together, these results indicate that both the O- and N-acetyl groups of the sialic acid residues of gangliosides turn over faster than the parent molecules. They also demonstrate a novel re-N-acetylation reaction that predicts the existence of de-N-acetyl gangliosides in melanoma cells. PMID- 2198285 TI - In vitro gamma-carboxylation of a 59-residue recombinant peptide including the propeptide and the gamma-carboxyglutamic acid domain of coagulation factor IX. Effect of mutations near the propeptide cleavage site. AB - We report the expression in Escherichia coli of a fusion protein that contains the propeptide sequence and gamma-carboxyglutamic acid domain (residues -18 to 41) of human factor IX (FIXGla). CNBr was used to release FIXGla from the fusion protein. The 59-amino acid peptide is an efficient substrate for in vitro gamma carboxylation. Its Km,app (0.55 microM) is several thousand-fold lower than that of the commonly used substrate FLEEL and about 5 times lower than proPT28 or proFIX28, (Hubbard, B. R., Jacobs, M., Ulrich, M. M. W., Walsh, C., Furie, B., and Furie, B. C. (1989) J. Biol. Chem. 264, 14145-14150). In addition, FIXGla is the first peptide substrate that is carboxylated in vitro to more than one gamma carboxyglutamic acid/molecule (6-11 gamma-carboxyglutamic acids/molecule). We created peptides with mutations identical to FIXSan Dimas or FIXCambridge as well as a peptide with both mutations in the propeptide sequence and examined the effect of the mutations on in vitro carboxylation. Enzyme kinetic studies revealed no significant difference in Vmax/Km values between normal and mutant substrates. Maximum carbon dioxide incorporation was achieved with the double mutant. From these data we conclude the following. 1) FIXGla and its mutants are excellent substrates for studying the mechanism of gamma-carboxylase. 2) Although arginines at positions -4 and -1 are highly conserved in the propeptide sequence of all the vitamin K-dependent proteins, neither is critical for gamma carboxylation. PMID- 2198286 TI - Elucidation of the deficiency in two yeast coenzyme Q mutants. Characterization of the structural gene encoding hexaprenyl pyrophosphate synthetase. AB - The assembly of a polyisoprenoid side chain and its transfer to para hydroxybenzoate are the first two steps of coenzyme Q biosynthesis. In yeast these reactions are catalyzed by hexaprenyl pyrophosphate synthetase and PHB:polyprenyltransferase, respectively. We have screened nine complementation groups of yeast coenzyme Q mutants for the activities of these two enzymes and found two strains deficient in either activity. The strain deficient in hexaprenyl pyrophosphate synthetase activity, C296-LH3, is complemented by the plasmid pG3/T1. When C296-LH3 was transformed with a shuttle vector containing a 2,187-base pair fragment from the genomic insert of pG3/T1, both glycerol growth and hexaprenyl pyrophosphate synthetase activity were restored. The activity of the latter enzyme was higher than that seen in wild-type yeast. The increase in activity could be attributed to a gene dosage effect of the multi-copy plasmid. A 1,419-base pair open reading frame encoding a 52,560-dalton protein was found on the genomic fragment. The size of the RNA transcript and the location of transcriptional initiation indicate that the entire open reading frame is contained within the mRNA. Comparison of the hexaprenyl pyrophosphate synthetase amino acid sequence with amino acid sequences from the related enzyme farnesyl pyrophosphate synthetase show the presence of three highly conserved domains. Within two of the domains is an aspartate-rich motif found invariantly in the amino acid sequences of farnesyl pyrophosphate synthetase from three species and the hexaprenyl pyrophosphate synthetase amino acid sequence reported here. These aspartic acid motifs may comprise binding sites for the allylic and homoallylic substrates. The hydrophobicity profiles of the hexaprenyl pyrophosphate synthetase sequence and the farnesyl pyrophosphate synthetase sequence from rat appear similar. Furthermore, the hydrophobicity correlation coefficient of the comparison of these two sequences indicate with a high degree of confidence (p less than 0.001) that the two proteins will fold into similar three-dimensional structures. PMID- 2198288 TI - Deletion analysis of the human insulin receptor ectodomain reveals independently folded soluble subdomains and insulin binding by a monomeric alpha-subunit. AB - A series of 13 deletions within the extracellular domain of the human insulin receptor delineates the boundaries of subdomains that fold de novo into stable proteins that are efficiently secreted and retain the epitopes required for interaction with two conformation-specific monoclonal antibodies. While most of these proteins fail to bind insulin, a truncation that includes only the alpha subunit is secreted as a monomer that binds the hormone with an affinity only slightly less than that of the complete heterotetrameric extracellular domain. These results thus demarcate landmarks within the primary sequence which will now guide further analysis of the structure and function of this complex domain of the receptor. PMID- 2198287 TI - Genetic reconstruction and characterization of the recombinant transacylase (E2b) component of bovine branched-chain alpha-keto acid dehydrogenase complex. Implication of histidine 391 as an active site residue. AB - Genetically altered transacylase (E2b) proteins of the bovine branched-chain alpha-keto acid dehydrogenase complex were overexpressed in Escherichia coli and characterized. Deletion by PstI or Bal31 digestion of the amino-terminal region of the inner-core domain (residues 175-421) beyond residue 209 resulted in a complete loss of transacylase activity. The enzyme assay was carried out using [1 14C]isovaleryl-CoA and exogenous dihydrolipoamide as substrates. The removal of 4 residues (Thr-Ile-Pro-Ile) (residues 175-178) from the amino terminus of the inner-core domain significantly reduced the level of transacylase activity. The results establish that the segment between residues 175 and 209 is an integral part of the active site of E2b. The residue His-391 in the recombinant inner-core domain (E2b delta 167) was changed to Asn or Gln by site-directed mutagenesis. The wild-type and the two mutant inner-core domains were assembled into 24-mers as determined by gel filtration. However, both Asn and Gln mutations were accompanied by a complete loss of the enzymatic activity. Titration of the natural branched-chain alpha-keto dehydrogenase complex from pH 8 to 6 sharply reduced transacylase activity. The above data support the hypothesis that a conserved histidine residue in E2 acts as a general base for the transacylation reaction by analogy with E. coli chloramphenicol acetyltransferases. PMID- 2198289 TI - LAC9 DNA-binding domain coordinates two zinc atoms per monomer and contacts DNA as a dimer. AB - The LAC9 protein of Kluyveromyces lactis activates transcription by binding to upstream activating sequences lying in front of genes of the lactose-galactose regulon. LAC9 belongs to a family of fungal proteins having a conserved domain containing 6 cysteines. This domain, termed a C6 zinc finger, is thought to bind one zinc atom and to play a vital role in DNA binding. To further characterize the DNA-binding domain of LAC9, we have developed a procedure to produce and to purify milligram amounts of LAC9 peptides. The two larger peptides, one containing amino acids 1-228 and the other containing amino acids 85-228, formed dimers in solution and bound DNA specifically as a dimer. The smallest LAC9 peptide, amino acids 85-160, failed to dimerize and did not bind DNA. Atomic absorption spectroscopy revealed that each LAC9 monomer coordinated two zinc atoms, not one, as had been predicted. This result suggests, as does previously published data, that the C6 zinc finger domain has a unique conformation that may represent a new type of DNA-binding motif. PMID- 2198290 TI - Expression of a synthetic gene for horseradish peroxidase C in Escherichia coli and folding and activation of the recombinant enzyme with Ca2+ and heme. AB - A synthetic gene encoding horseradish peroxidase isoenzyme C (HRP C) has been synthesized and expressed in Escherichia coli. The nonglycosylated recombinant enzyme (HRP C*) was produced in inclusion bodies in an insoluble inactive form containing only traces of heme. HRP C* was solubilized and conditions under which it folded to give active enzyme were determined. Folding was shown to be critically dependent upon the concentrations of urea, Ca2+, and heme and on oxidation by oxidized glutathione. Purification of active HRP C* from the folding mixture gave a peroxidase, with about half the activity of HRP C. Glycosylation is thus not essential for correct folding and activity. The C-terminal and N terminal extensions to HRP identified previously in cloned cDNA sequences are also not required for correct folding. However, Ca2+ appears to play a key role in folding to give the active enzyme. The overall yield of purified active enzyme was 2-3%, but this could be increased by reprocessing material that precipitated during folding. PMID- 2198292 TI - Essential role for induced Ca2+ influx followed by [Ca2+]i rise in maintaining viability of yeast cells late in the mating pheromone response pathway. A study of [Ca2+]i in single Saccharomyces cerevisiae cells with imaging of fura-2. AB - We established an experimental system for measuring the cytosolic-free Ca2+ concentration ([Ca2+]i) in individual Saccharomyces cerevisiae cells using fura-2 as a Ca2(+)-specific probe in conjunction with digital image processing and examined changes in [Ca2+]i in response to alpha-factor in single cells of a mating type. The addition of alpha-factor to a cells raised [Ca2+]i to several hundred nanomolar in the cells from a basal level of approximately 100 nM, simultaneous with the induction of Ca2+ influx. When the cells were incubated with alpha-factor in a Ca2(+)-deficient medium, Ca2+ influx was greatly reduced, and the rise in [Ca2+]i was not detected. This indicates that the alpha-factor induced rise in [Ca2+]i is generated by Ca2+ influx through the plasma membrane and not by release from internal stores. In the Ca2(+)-deficient medium, a cells died specifically after they had changed into cells with one projection on the cell surface. This indicates that the rise in [Ca2+]i is essential for the late response to alpha-factor. The duration of Ca2+ requirement for maintaining viability was limited to this stage, and the earlier and later stages were not affected by Ca2+ deprivation. Mating between a and alpha mating type cells was impaired in this medium due to cell death at and before the stage of conjugation. These findings are the first evidence for an essential role for mobilized Ca2+ in the yeast life cycle. PMID- 2198291 TI - Structural and functional studies of Saccharomyces cerevisiae myristoyl CoA:protein N-myristoyltransferase produced in Escherichia coli. Evidence for an acyl-enzyme intermediate. AB - Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase has been efficiently expressed in Escherichia coli and subsequently purified to homogeneity using phosphocellulose chromatography. The interactions between apoenzyme and its acyl-CoA and peptide ligands were examined by an isoelectric focusing gel shift assay, circular dichroism, and fluorescence spectroscopy, and a continuous assay of enzyme activity which measures the release of CoA from acyl CoA using the thiol-specific reagent 5-5'-dithiobis-2-nitrobenzoate. Addition of myristoyl-CoA (without a substrate peptide) results in the formation of a high affinity reaction intermediate which can be operationally defined by the appearance of a more acidic enzyme isoform and by quenching of the tryptophan emission with a maximal difference at 340 nm. Circular dichroism spectroscopy indicates that these changes are accompanied by minimal changes in the enzyme's secondary structure. Incubation of purified NMT with [1-14C] myristoyl-CoA, followed by chymotryptic digestion, denaturing polyacrylamide gel electrophoresis, and treatment with hydroxylamine yielded results that are highly suggestive of a covalent ester-linked acyl-enzyme complex. Edman degradation of chymotryptic peptides has narrowed the site of interaction to a domain spanning Arg42 to Thr220 of the 455 amino acid acyltransferase. An octapeptide containing Gly but not Ala at position 1 is able to reverse the change in pI and reduce the quenching almost entirely. These data suggest a preferred order or ping-pong reaction mechanism with the acyl-CoA substrate binding event occurring first. They also indicate that Gly1 is absolutely necessary for the reaction to proceed forward from the acyl-enzyme reaction intermediate. PMID- 2198293 TI - Lipid-vesicle-surface chromatography. AB - Egg-yolk phospholipid vesicles (liposomes) containing stearylamine cations or phosphatidylserine anions, were formed and entrapped in agarose gel beads (Sepharose 6B) by a dialysis procedure. On a column of entrapped phospholipid stearylamine (4:1) (cationic) vesicles, 0.36 mg of ferritin was bound per mumol lipids at 0.05 M ionic strength and pH 7. About 30% of the vesicle surface thus became covered with ferritin. Only 0.04 mg of citraconylated myoglobin was bound per mumol lipids, as myoglobin is much smaller than ferritin. Haeme groups were readily inserted into the lipid bilayers. An excess amount of bovine serum albumin (BSA) or ribonuclease A was applied to entrapped ionic vesicles and the bound proteins were eluted by increasing the ionic strength from 0.01 to 0.2 or 0.5 M. After three to five runs, 82-88% of the vesicles (the phospholipids) remained entrapped. The capacity of the cationic vesicle-column for BSA decreased more than did the amount of entrapped vesicles, which indicates a preferential loss of stearylamine. Ion-exchange experiments were done with human plasma and with BSA monomers and dimers on entrapped cationic vesicles. Plasma proteins could be separated. BSA dimers were eluted later than BSA monomers in a sodium chloride gradient and the separation was better than on DEAE-Sepharose. The contact area between the protein and the vesicle surface is important for the binding strength. Protein-vesicle surface interactions can be studied by chromatography on entrapped vesicles. PMID- 2198294 TI - Dose-response evaluation of the amnestic effects of triazolam and pentobarbital in normal subjects. AB - The effects of placebo, triazolam (0.25, 0.5, and 0.75 mg), and pentobarbital (100, 200, and 300 mg) were examined in seven normal male volunteers using a double-blind, Latin Square, balanced crossover design. Before and at hourly intervals after oral drug administration at approximately 10 a.m., subjects completed subject ratings of drug effects, psychomotor performance tasks, and two versions of a number recall task in which eight-digit number stimuli were recalled by reproduction on a numeric keypad. In one version, number stimuli were displayed on a video screen for varying lengths of time (3, 6, or 9 seconds) before immediate recall. In another version, subjects initially reproduced a continuously displayed number and then recalled the number following an immediate or a 16-second delay interval. Both triazolam and pentobarbital produced dose related effects on all measures. Relative potency comparisons showed that triazolam was 270-384 times more potent than pentobarbital on subject ratings and psychomotor measures but was 406-647 times more potent than pentobarbital on measures of recall impairment. Recall performance deficits produced by both triazolam and pentobarbital at short (3-second) stimulus presentation times were attenuated at longer presentation times. With the variable delay task, triazolam but not pentobarbital interacted with the delay interval and produced impairments only at the 16-second delay condition. These data indicate that both triazolam and pentobarbital quantitatively impair acquisitional processes involved in short term recall performance. Furthermore, triazolam may have a greater potential than pentobarbital to produce memory impairment, as reflected by its greater relative potency on these measures and its tendency to interfere with retention over short delay intervals. PMID- 2198295 TI - Effects of fenfluramine on neuropsychological and communicative functioning in treatment-refractory schizophrenic patients. AB - Reported behavioral improvement among autistic patients following feufluramine treatment and a high serotonin level among certain chronic schizophrenic patients suggested that fenfluramine treatment might be beneficial with such schizophrenic patients, especially within the realm of neuropsychological and communicative functioning. A brief neuropsychological battery was administered to eight chronic schizophrenic subjects before, during, and after fenfluramine treatment. Conversations in controlled settings were audiotaped before and during fenfluramine treatment for seven of these subjects and one additional subject. These language samples were analyzed for communicative competence and evidence of thought disorder. Overall, neuropsychological and communicative functioning was worse under the fenfluramine condition, even though blood serotonin levels were about half those at baseline conditions. The results suggest that it is not the higher levels of blood serotonin by themselves that are related to depressed neuropsychological, communicative, and other functioning. In fact, the higher levels of serotonin may well be related to adaptations for maximal level of functioning. These results suggest caution in the use of fenfluramine for other schizophrenic populations. PMID- 2198296 TI - Transient insomnia associated with a 3-hour phase advance of sleep time and treatment with zolpidem. AB - A 3-hour phase advance of sleep time was employed to produce a model of transient insomnia. The degree to which this manipulation was effective varied substantially among young, healthy normal sleepers. Zolpidem, an imidazopyridine hypnotic compound, was effective in reversing the sleep disruption in those individuals displaying transient insomnia in this model. PMID- 2198297 TI - Preference for diazepam in anxious adults. AB - This study investigated whether anxious adults desiring treatment for their anxiety would choose to take 10 mg of diazepam (Valium) or placebo after sampling both substances under double-blind conditions. Subjective effects of the drugs were also assessed, and the relationship between self-reported subjective effects and the number of times subjects chose diazepam or placebo was examined. Fourteen male and female volunteers meeting criteria for generalized anxiety disorder were recruited. They participated in a nine-session choice experiment in which they sampled diazepam 10 mg and a placebo on the first four sessions and chose whichever they preferred on the next five sessions. Only three subjects chose diazepam on all five choice occasions, no subjects chose diazepam on three or four occasions, and 11 subjects chose diazepam on two or fewer occasions. Overall, diazepam produced typical, tranquilizer-like subjective effects. However, subjective responses to diazepam differed in the 0-2-time choosers compared with the 5-time choosers: the 0-2-time choosers showed an increase on the measure of confusion, while the 5-time choosers showed decreases on measures of anxiety and confusion and increases on measures of stimulation. PMID- 2198298 TI - Fluoxetine drug-drug interactions. II. PMID- 2198299 TI - Serotonin: a common neurobiologic substrate in anxiety and depression. AB - Anxiety and depression have traditionally been considered independent pathologies. Recent evidence suggests that these disorders may be related. Some tricyclic antidepressant drugs appear to be effective against generalized anxiety disorders in man, and in animal models, chronic administration of some anxiolytic drugs produces activities predictive of antidepressant potential. It is proposed that imbalances in serotonergic neurotransmission may contribute significantly to both pathologies and that agents that act as serotonin partial agonists may normalize neurotransmission in both serotonin deficit (depression) and excess (anxiety) diseases. The azapirones, a new class of drugs that includes buspirone, ipsapirone, and gepirone, act as serotonin partial agonists at the serotonergic type1A receptor, and may prove useful in treating multiple psychopathologies characterized by aberrant serotonin neurotransmission. PMID- 2198300 TI - Comorbidity of anxiety and depression. AB - Many factors obscure the diagnosis of psychogenic disorders, especially anxiety and depression. The factors involved include an overlap of symptoms, discrepancies in diagnostic criteria, and the unreliability of self- and observer reporting. Differentiation among the various personality disorders is, however, extremely important, both for identifying the most appropriate treatment plan for a given patient and for evaluating the therapeutic activity of newly developed pharmacologic agents. Emerging factors that may have an impact on differential diagnoses of anxiety and depression include age at onset, family history, and personality traits associated with different types of psychopathology. PMID- 2198301 TI - Buspirone therapy in anxious elderly patients: a controlled clinical trial. AB - Forty patients over 65 years of age with anxiety symptoms due to an anxiety state (N = 20) or secondary to neurotic depression (N = 20) took part in a double blind, placebo-controlled trial conducted in a primary care practice. All patients were receiving concomitant drug therapy for chronic medical conditions; 70% were receiving two or more nonpsychotropic drugs in addition to the study medication. Patients were randomly assigned to treatment with buspirone 5-30 mg/day or placebo for 4 weeks, with clinical evaluations made weekly. One buspirone-treated and two placebo-treated patients discontinued treatment after 2 weeks because of lack of efficacy. Buspirone treatment resulted in significantly greater (p less than or equal to 0.05) improvement on the Hamilton Rating Scale for Anxiety, Hamilton Rating Scale for Depression, and Clinical Global Impression assessment than did placebo. Mild adverse experiences were reported by five buspirone-treated and nine placebo-treated patients. Buspirone (mean dose, 18 mg/day) proved equally effective for elderly patients suffering anxiety states or neurotic depression at doses similar to those used in younger patients, and was well tolerated by elderly patients receiving treatment for other chronic medical conditions. PMID- 2198302 TI - Anxiety and depression: discrete diagnostic entities? AB - Some forms of anxiety and affective disorder, such as panic disorder and major depression, appear distinct, while other forms, such as generalized anxiety disorder and chronic depression or dysthymia, may lie on a continuum and blend with each other. However, even panic disorder and major depression have many common features. Moreover, for reasons not yet clear, they occur together frequently, and their combined occurrence in the same patient has been associated with greater severity and chronicity, decreased treatment responsiveness, and, possibly, increased familial prevalence of anxiety and/or depression. Finally, studies of primary care patients suggest the frequent occurrence of a mixed anxiety-depressive disorder that may often be subsyndromal by DSM-III-R criteria but is nevertheless associated with prominent distress and/or impairment. PMID- 2198303 TI - Clinical effects of the 5-HT1A partial agonists in depression: a composite analysis of buspirone in the treatment of depression. AB - The azapirone class of anxiolytic drugs is being evaluated for clinical use in the treatment of depression. Buspirone, a serotonin (5-hydroxytryptamine, 5-HT) partial agonist active at the 5-HT1A receptor subtype, was evaluated in the treatment of depression in a series of five placebo-controlled, parallel group studies involving 382 patients with DSM-III major depression and significant associated anxiety symptoms (both Hamilton depression [HAM-D] and Hamilton anxiety [HAM-A] scales greater than or equal to 18). Buspirone therapy was initiated at 15 mg/day with individual dose titration to a maximum of 90 mg/day and resulted in marked improvement in both depressive and anxiety symptoms. Analyses of the composite data base from the five studies show significant (p less than 0.05) improvement in mean HAM-D, HAM-A, and Clinical Global Impression Global Improvement scale ratings for buspirone-treated compared with placebo treated patients. Of particular interest was significant improvement in cardinal depression symptoms, e.g., depressed mood, guilt, work and interest, anergia, and diurnal variation of mood. Subset analyses revealed that patients with melancholic-type major depression and patients with more severe symptoms (judged by higher initial HAM-D or HAM-A total scores) responded better to buspirone than did patients who were less ill. The buspirone dose most frequently associated with clinically significant improvement was 40 mg/day. Gepirone, an analogue of buspirone with highly selective binding affinity for the 5-HT1A receptor subtype, also shows promise of antidepressant efficacy in preliminary controlled clinical trials. These data suggest that azapirones, which as partial agonists modulate 5 HT1A receptor function, have clinically important antidepressant properties. PMID- 2198304 TI - Quantitative genetic tools for insecticide resistance risk assessment: estimating the heritability of resistance. AB - Quantitative genetic studies of resistance can provide estimates of genetic parameters not available with other types of genetic analyses. Three methods are discussed for estimating the amount of additive genetic variation in resistance to individual insecticides and subsequent estimation of the heritability (h2) of resistance. Sibling analysis and offspring-parent regression permit direct estimates of h2 by comparing the resistance phenotypes of individuals of known relatedness. Threshold trait analyses, performed on data from selection experiments, provide estimates of realized heritability. Procedures are outlined for predicting changes in resistance to insecticides based on h2 estimates. Quantitative genetic theory is examined as it relates to resistance and resistance as a quantitative trait; quantitative genetic methods also are unique in providing estimates of genetic correlations between traits. Comments are included on estimates of genetic correlation between resistance and phenotypic traits (e.g., development time) and how they may be used to predict changes in the genetic aspects of phenology that result from insecticide applications (i.e., to predict how the reproductive capacity of future generations will differ from that of the treated generation). PMID- 2198305 TI - Inquiry, insights, and history. The making of history. PMID- 2198306 TI - Historical roots and future perspectives related to nursing ethics. AB - This article traces the evolution of the development and the refinement of the professional code from concerns about the ethical conduct of nurses to its present state as a professional code for all nurses. The importance and the relationship of the Ethics Committee of the American Nurses' Association (ANA) to the development of the code and other ANA programs and structural units is also presented. The recognized need for a code of ethics to establish nursing as a profession has been present throughout the evolution of the professional nursing organization. A distinction between ethical conduct of nurses and a code of ethics for professional nurses has been made by nursing leaders. The code has been refined to reflect nursing's changing relationship to society and the societal concerns of the times. PMID- 2198307 TI - On the nature and place of empathy in clinical nursing practice. AB - Empathy has long been thought of as a fundamental component of nurse-patient interactions. Despite the central role empathy has been accorded, understanding how the concept is operationalized in practice is difficult. A review of nursing literature on empathy is presented to help clarify the concept, and an analysis is given concerning the relationship of empathy to recent findings on expert caring in nursing. Vignettes are presented as illustrations of the concepts discussed. PMID- 2198308 TI - Social judgment processes in hyperactive boys: effects of methylphenidate and comparisons with normal peers. AB - Although there is consensus that ADHD children have serious social problems, there is little understanding of the mechanisms underlying or accompanying such problems. To examine the possibility of atypical or faulty social reasoning, we presented ADHD and normal boys with a social perception task that entailed evaluating the behaviors of unknown peers. ADHD "judges" participated under both methylphenidate and placebo conditions, and on each occasion they evaluated an unfamiliar ADHD "target" in each medication state. In contrast to placebo, methylphenidate appeared to dampen overall response rates in ADHD judges, but there was no effect on sensitivity to medication-related differences. Regardless of their own medication state, ADHD judges identified more undesirable behaviors in peers on placebo than in those taking methylphenidate. Judges with the most serious behavior problems tended to identify the greatest number of negative behaviors in peers, especially when both judge and target were unmedicated. There were no effects of target medication status on detections of positive behaviors and few differences in detection patterns of ADHD versus normal judges. Discussion focused on the need to distinguish general regulatory from specific social-cognitive processes. PMID- 2198309 TI - Emporiatrics: protecting travelers from malaria. AB - Travelers to malarious areas of the world should take precautions against mosquito bites and take medications to prevent the disease. Chloroquine is the prophylactic agent of choice in areas where malaria remains sensitive. If no contraindications exist, mefloquine is recommended in areas where chloroquine resistance occurs. Alternative regimens would include doxycycline taken as the sole prophylactic agent, or weekly chloroquine with a treatment dose of Fansidar to be taken if symptoms compatible with malaria occur. PMID- 2198310 TI - Practical considerations in designing data collection forms. PMID- 2198311 TI - Head and neck cancers: results of thermoradiotherapy versus radiotherapy. AB - Sixty-five patients were included in a randomized clinical study to evaluate the efficacy of local hyperthermia as a concomitant agent to radiotherapy in the treatment of carcinoma of the head and neck region. Local hyperthermia at 42-43 degrees C was generated by a 27 x 12 MHz radiofrequency diathermy unit and was used before radiotherapy in 33 patients; the remaining 32 patients were subjected to radiotherapy alone. The response in patients with early lesions (Stage I and II) was similar for both the groups, while in patients with advanced disease (Stage III and IV) a significantly better tumour control was obtained by the use of the combined treatment. PMID- 2198312 TI - Treatment of disseminated malignant melanoma with cisplatin in combination with whole-body hyperthermia and doxorubicin. AB - Twenty-three patients with disseminated malignant melanoma were entered in a pilot study conducted from January 1983 to January 1988. There were 14 men and nine women. Fifteen patients were available for final evaluation. The criterion for evaluation was the completion of the two thermochemotherapy cycles. Patients received multiple-drug chemotherapy consisting of cisplatin (80 mg/m2, i.v., day 1) and doxorubicin (50 mg/m2, i.v., day 2); applications were repeated on days 22 29. Cisplatin was administered concurrently with whole-body hyperthermia (WBH) on day 1 (body core temperature 41 +/- 0.5 degrees C/h). The following response rates were achieved: complete remission (CR) 0/15; partial remission (PR) 3/15; minor response (MR) 4/15, no change (NC) 3/15; progressive disease (PD) 5/15. These findings are within the range known from the literature of the response to multiple-drug chemotherapy without hyperthermia. Toxicity, in particular renal toxicity, was not enhanced by the combined application of cisplatin and hyperthermia, with the exception of the bone marrow toxicity, which seemed to be slightly more pronounced than that known from normothermic application. Concurrent administration of thermochemotherapy with cisplatin and WBH (41 +/- 0.5 degrees C/h) is no more effective than the multiple-drug chemotherapy without hyperthermia as reported in the literature. PMID- 2198314 TI - Controlled clinical trial of two multidrug regimens with and without rifampin in highly bacilliferous BL/LL south Indian patients: a five-year report. AB - A controlled clinical trial of two multidrug regimens in multibacillary lepromatous and near-lepromatous patients with a bacterial index (BI) of 2.5 or more was conducted. Patients were randomly allocated to either a two-drug regimen of dapsone plus clofazimine for 60 months or a four-drug regimen of rifampin, isoniazid, dapsone, and clofazimine for the first 3 months and clofazimine plus dapsone for the next 57 months. There was no difference between the rifampin and nonrifampin regimens with respect to the clinical improvement or bacteriological status of the patients at 60 months. Reactive states and neuritis were observed to be equal in the two patient groups. PMID- 2198313 TI - Effects of heat and other agents on amino acid uptake in Escherichia coli. AB - In Escherichia coli K1060 grown at 37 degrees C we observed that the uptake of both L-[3H]leucine and L-[35S]methionine was inhibited by exposure of the cells to 48 degrees C. The calcium channel blockers diltiazem and verapamil, and the anti-arrhythmic agent quinidine, inhibited the uptake of L-[3H]leucine at both 37 degrees C and 48 degrees C. Verapamil also inhibited the uptake of L [35S]methionine at 37 degrees C, but at 48 degrees C protected against some of the heat-induced decrease in the uptake of this amino acid. The local anaesthetic procaine markedly inhibited the uptake of both labelled amino acids at temperatures between 37 degrees C and 48 degrees C. Amino acid uptake and cell killing were not correlated. PMID- 2198315 TI - Clinical trial of pefloxacin and ofloxacin in the treatment of lepromatous leprosy. AB - Twenty-one previously untreated lepromatous patients were randomized into two groups and treated with either 800 mg pefloxacin (PEFLO) or 400 mg ofloxacin (OFLO) once daily. The trial consisted of two parts: monotherapy from day 0 to day 56; and combined with the World Health Organization multidrug therapy (WHO/MDT) regimen for multibacillary (MB) leprosy from day 57 to day 180. Four patients were removed from the trial because the organisms recovered from their pretreatment biopsies failed to infect mice. Among the remaining 17 cases, four (23.5%) had primary resistance to dapsone but all of them were susceptible to rifampin. The initial (day 0) proportion of viable organisms, as measured by mouse foot pad inoculation, varied tremendously from patient to patient despite randomization during admission. Definite clinical improvement was noticed in virtually all patients after 22 doses of treatment with either PEFLO or OFLO. A significant fall in the morphological index (MI) occurred as early as after 8 doses of PEFLO or after 22 doses of OFLO; the bacterial load also showed a moderate degree of reduction during the period of monotherapy. Although single dose PEFLO or OFLO displayed only a modest degree of bactericidal effect against Mycobacterium leprae, about 99.9%, or 4 logs, of organisms viable on day 0 were killed by 22 doses of either PEFLO or OFLO. No significant difference in the therapeutic effect was detected between the two regimens. During PEFLO or OFLO monotherapy, except in one patient (case no. 10), the side effects were few and mild. Case no. 10 developed a psychic disorder after 27 days of PEFLO monotherapy, presumably due to the treatment with PEFLO. All of the patients tolerated the period of combined therapy extremely well, although some asymptomatic and transient laboratory abnormalities were observed. Because both PEFLO and OFLO displayed rapid bactericidal activities in human leprosy and were well tolerated by the patients, further clinical trials and field trials in evaluating the therapeutic effects of combined regimens containing both rifampin and PEFLO or OFLO are being organized. Since this is the first clinical trial in leprosy employing nude mice, in combination with normal mice, for monitoring the therapeutic effects of antimicrobials, the advantages, limitations and appropriate timing in using nude mice are discussed. PMID- 2198316 TI - Rapid serodiagnosis for leprosy--a preliminary study on latex agglutination test. AB - In this study, we have developed two latex agglutination tests (LATs) with phenolic glycolipid-I (PGL-I) and natural disaccharide-octyl-bovine serum albumin (ND-O-BSA) as antigens in 110 leprosy patients (LL = 30, BL = 30, BT = 30, and TT = 20), 50 tuberculosis cases, and 30 normal controls. These two LATs were compared with corresponding ELISAs (ND-O-BSA ELISA and PGL-I ELISA) and analyzed by the chi-squared test. There were no significant differences between the two LATs (PGL-I LAT and ND-O-BSA LAT) and their corresponding ELISAs. There was an increase in the proportion of positive cases detectable which coincided with the clinical classification of leprosy, i.e., lepromatous cases were more likely to be positive than tuberculoid cases. LATs are more simple and rapid than ELISAs and have high sensitivity (77% in ND-O-BSA LAT, 80.5% in PGL-I LAT) and specificity (99% in both LATs). LATs may become useful tools for the immunodiagnosis of leprosy in the field. The stability and repeatability of LATs are discussed in detail. PMID- 2198317 TI - A quantitative study of the relationship between systemic and histological parameters of immunity in individual leprosy patients. AB - A group of 52 untreated leprosy patients were examined to determine the relationship between local and systemic immunological parameters across the clinico-pathological spectrum. The Ridley-Jopling classification, bacterial index (BI), and granuloma fraction (GF) were assessed in biopsies from 40 cases. The densities of apoptoses, mitoses, and plasma cells were also measured. Systemic immunity to mycobacteria was assessed by skin tests with leprosin A and PPD, and by measurement of the serum antibody responses to Mycobacterium leprae, M. tuberculosis, and M. scrofulaceum. The serum responses to phenolic glycolipid-I (PGL-I) of M. leprae was assessed using a glycoconjugate which mimics an immunodominant epitope. The serum antibody levels and skin test results showed the expected inverse relationship. The BI within lesions showed an inverse correlation with the skin test results, but none of the other histological parameters studied showed a significant relationship with the other measurements of systemic immunity. Our findings suggest that the inverse relationship between delayed-type hypersensitivity and humoral immunity in leprosy patients, which is strong in groups of patients across the leprosy spectrum, is less strong in individual patients than is often thought. The lack of correlation of many histological and systemic parameters suggests that local factors modulate systemic immunity in the pathogenesis of leprosy lesions. PMID- 2198318 TI - Controlled clinical trials. PMID- 2198319 TI - Extreme hyperferremia in two instances of hemochromatosis with notes on the treatment of one patient by means of repeated venesection. 1952. PMID- 2198320 TI - George E. Cartwright, MD (1917-1980). PMID- 2198321 TI - Fibrin polymerization and its regulatory role in hemostasis. AB - Proteolytic conversion of fibrinogen to fibrin results in self-assembly to form a three-dimensional clot matrix that subsequently becomes cross-linked by fXIIIa to form the central structural element of the in vivo thrombus. The process of fibrin formation and assembly leads to new properties that serve to regulate the rate and extent of clotting, cross-linking, and fibrinolysis. These are brought about by the ability of fibrin (1) to bind thrombin at a noncatalytic site, thus limiting its diffusability but at the same time preserving its catalytic potential; (2) to bind fXIII, regulate its activation to fXIIIa, and limit further activation of fXIII once fibrin cross-linking has occurred; and (3) to bind alpha 2-PI, tPA, and plasminogen and regulate the initiation and propagation of fibrinolysis. Additional interactions not covered in this review between fibrin(ogen), and other plasma proteins, cells or matrix components suggest other functions for fibrin that, along with those discussed above, define a critical role in modulating hemostasis, inflammation, and the wound healing process. PMID- 2198322 TI - Reliability of conventional ear swabs in tubotympanic CSOM. AB - Conventional external ear swab cultures were compared with cultures obtained from the middle ear, in 25 cases of tubotympanic type ('safe'), chronic suppurative otitis media. These cultures were identical in 22 of the 25 cases. Anaerobic organisms were isolated in only one case. Mixed infections of both gram-positive and gram-negative organisms were seen in nine cases (36 per cent). Staphylococcus aureus was the commonest single agent isolated (16 cases). Multidrug resistance was seen in 12 of these isolates. PMID- 2198323 TI - Addressing the issue of cataloging and making chiropractic literature accessible: Part I: Defining the problem. AB - Health science journals are a principle source of new knowledge for chiropractors, chiropractic faculty and students. Regrettably, clinically or educationally relevant articles (appearing in the nearly 20,000 journals annually) are often overlooked due to access difficulties. Innovations are needed to assist the reader to select articles relevant to chiropractic and reduce the time spent sorting through the volumes of literature. A review of the literature shows there is a trend toward database management for cataloging and accessibility of other, nonchiropractic, literature. Most notable of these is an endeavor by National Technical Information Service, commonly referred to as MEDLARS (Medline). It is interesting to note that a computer-assisted library database program does not exist on any chiropractic campus. This is in contrast with the trend on campuses of other health care fields. Manual search strategies within the chiropractic literature are time consuming, subject to a high failure rate, and even if the search produces citations, there is no assurance the journal can be accessed unless a chiropractic campus is nearby. Furthermore, difficulties exist when a chiropractic literature search is attempted in any computerized database, e.g., MEDLARS (Medline). Journals/articles that are unique to chiropractic (national, international or on the state level) are not specifically included in these computerized databases. Aside from these difficulties, there exists the problem of finding those articles that contain valid and relevant information from among those that are less valid or informative. PMID- 2198325 TI - Hepatitis B virus DNA in peripheral blood leukocytes: a brief review. AB - Despite being essentially hepatotropic, hepatitis B virus has frequently been detected in peripheral blood leukocytes. In most cases, viral DNA has been detected by hybridisation, though, occasionally, evidence of viral RNA and virus specific proteins has been reported. Though definitive evidence is lacking, it appears likely that the virus is able to replicate in at least a subfraction of these cells. The possible consequences with respect to the transmission and reactivation of virus infections are discussed. PMID- 2198324 TI - Occupational repetitive motion injury: clinical overview and chiropractic implication. AB - Repetitive motion injury of occupational etiology provides chiropractic an opportunity to expand its clinical use to both industry as well as its patients. An overview of repetitive motion injury is presented including workplace epidemiology, pathophysiology and risk factor assessment. A coordinated plan of action aimed at reducing repetitive motion injury incidence through engineering controls, patient education and clinical therapeutics is offered. PMID- 2198326 TI - Molecular mechanisms of nucleic acid integration. AB - There are three known mechanisms by which foreign DNA can be made a permanent part of the genome of an animal cell, and their properties are summarized in this report. Naked DNA introduced into cells is usually rapidly lost, but a small fraction can be integrated by illegitimate recombination, usually accompanied by major and unpredictable rearrangements in both inserted DNA and target. This mechanism, although inefficient and disruptive, accounts for virtually all integrated DNA seen in virus infections, and is often used for making cell lines carrying specific genes as well as transgenic mice. Homologous recombination between inserted and resident DNA is much rarer but can be detected and put to use. The best understood mechanism is that employed by retroviruses and related elements. In contrast to the other mechanisms, retroviral integration results in a predictable, stable association between virus and cell DNA with only minor sequence changes. However, it occurs only when the DNA is derived by reverse transcription of the RNA in an incoming viral particle and contains the correct sequences at its ends. Thus, from a standpoint of vaccine safety, only the first of the three mechanisms is at all relevant. Based on some prior experimentation in animals, the risk of introduction of activated oncogenes or other dangerous sequences by this means is extremely small. PMID- 2198327 TI - History, precedent, and progress in the development of mammalian cell culture systems for preparing vaccines: safety considerations revisited. AB - The use of cell substrates to propagate viruses or recombinant plasmids for vaccine productions has been the subject of long evolutionary conflict, primarily from the standpoint of product safety, and especially from the viewpoint of cancer induction. The present concern is for safety of vaccines made using transformed or neoplastic mammalian cells that may contain endogenous contaminating viruses or integrated gene sequences from oncogenic viruses. There is also concern for use of plasmid vectors employing promoter elements from oncogenic viruses. The principal concern for safety lies with retention of residual DNA in the vaccine, especially since induction of cancer is a single cell phenomenon, and a single functional unit of foreign DNA integrated into the host cell genome might serve to induce cell transformation as a single event or part of a series of multifactorial events. Current proposed standards for vaccines would permit contamination with up to 100 pg of heterologous DNA per dose. This is equivalent to about 10(8) "functional lengths" of DNA. Total safety would seem to require complete absence of DNA from the product. While preparation of biologicals used to treat serious disease might demand the use of mammalian cells, this is not the situation with vaccines that are given prophylactically to persons who might be given equally efficacious vaccines produced in bacterial cells or in yeast that have attributes for greater safety. Careful assessment of safety and risk vs. benefit of continuous mammalian cell-produced vaccines should be made by technically expert scientists in the relevant disciplines and a consensus needs to be evolved in the scientific community at large. PMID- 2198328 TI - Risk of tumor induction in vivo by residual cellular DNA: quantitative considerations. AB - Certain genes, termed oncogenes, have the ability to transmit the transformed phenotype from tumor cells to hitherto normal cells in vitro and in vivo. This observation is the basis for the concern that medicinal products derived from tumor cell lines could contain possibly tumorigenic contaminating cellular DNA. A comparison between the number of oncogenes necessary for the induction of tumors in a suitable animal model and the quantity in 100 pg residual cellular DNA was carried out. It is shown that the latter contains less than a billionth of the number needed to induce tumors in half of the animals tested. Some factors implicit to this calculation such as the validity of the model system, the linearity of the dose response curve, the concept of multistep carcinogenesis, the amplification of oncogenes, and the transfection enhancing effect of other constituents of the drug are discussed. In summary, 100 pg residual cellular DNA per dose seems to be a safe and, therefore, an acceptable upper limit provided that some factors such as excessive amplification of oncogenes, co-purification of oncogenic DNA with the product or some transfection mediating activity can be excluded. PMID- 2198329 TI - Repeat pregnancy among adolescent mothers: a review of the literature. AB - Repeat pregnancy among adolescent mothers is a major problem facing healthcare providers today. Adolescents who experience multiple pregnancies often are subjected to overwhelming physical, social, economic, and psychological outcomes. Research is needed to investigate the problem of repeat pregnancy and provide empirical support for intervention programs developed to reduce the incidence. This paper is a review of previous research. Major factors related to repeat pregnancy are examined. In addition, recommendations for future research are discussed. PMID- 2198330 TI - Sexual issues and research in counseling the postmyocardial infarction patient. AB - This article reviews the literature relevant to the postmyocardial infarction (MI) patient and sexual activities. It begins with an analysis of the published accounts of the physiologic effects of sexual activity (including intercourse) and the anticipated concerns associated with coital deaths. The article includes an examination of the need for sexual counseling in any treatment and rehabilitation setting. In addition, general sexual adjustment guidelines for the uncomplicated post-MI patient are presented. PMID- 2198331 TI - Color and contrast sensitivity in the lateral geniculate body and primary visual cortex of the macaque monkey. AB - We tested color and contrast sensitivity in the magnocellular and parvocellular subdivisions of the lateral geniculate body and in layers 2, 3, 4B, and 4C alpha of visual area 1 to obtain physiological data on the degree of segregation of the 2 pathways and on the fate of the color and contrast information as it is transmitted from the geniculate to the cortex. On average, magnocellular geniculate cells were much less responsive than parvocellular cells to shifts between 2 equiluminant colors. Nevertheless, many magnocellular cells (though not all) continued to give some response at equiluminance. As expected from previous studies, luminance contrast sensitivity differed markedly between magnocellular and parvocellular layers. In V-1, the properties of cells in the magnorecipient layers 4C alpha and 4B faithfully reflected the properties of magnocellular geniculate cells, showing no evidence of any parvocellular input. Like magnocellular geniculate cells, they showed high contrast sensitivity, and with color contrast stimuli they showed large response decrements at equiluminance. In the interblob regions of cortical layers 2 and 3, which anatomically appear to receive most of their inputs from parvorecipient layer 4C beta, contrast sensitivities of some of the cells were compatible with a predominantly parvocellular input. Other interblob cells had sensitivities intermediate between magno- and parvocellular geniculate cells, suggesting a possible contribution from the magnocellular system. Many cells in cortical layers 2 and 3 responded to color-contrast borders equally well at all relative brightnesses of the 2 colors, including equiluminance. We recorded from many direction- and disparity-selective cells in V-1: most of the direction-selective and all of the clearly stereo selective cells were located in layer 4B. PMID- 2198332 TI - Cocaine use during pregnancy. Research findings and clinical implications. AB - Cocaine's popularity has escalated drastically within the past decade, and pregnant women from all socioeconomic, racial, and cultural groups are among the burgeoning number of users. The pharmacologic properties of this highly addictive, mind-altering drug and its profound effects on the pregnant woman and fetus are presented. Recent clinical research findings on cocaine use during pregnancy are reviewed, implications for nursing care are examined, and specific nursing interventions are identified. PMID- 2198333 TI - Systemic lupus erythematosus during pregnancy. AB - Today, more women with systemic lupus erythematosus are opting for pregnancy than in the past. Nurses need to be familiar with maternal, fetal, and neonatal manifestations of the disease, as well as antenatal surveillance and treatment options. A review of the literature outlines current pharmacologic management and provides the basis for both medical and nursing considerations. PMID- 2198334 TI - Surfactant for neonatal respiratory distress syndrome. PMID- 2198335 TI - Toward a biologically informed psychology of personality. AB - This article describes nine ways in which biological approaches can inform issues of central and long-standing concern to personality psychologists. These include: (a) developing an adequate description of human nature, (b) providing several solutions to the puzzle of within-species genetic variability, (c) identifying the most important ways in which individuals differ, (d) giving precision to the concepts of adaptation and adjustment, (e) identifying the origins of personality dispositions, (f) providing insight into personality development and the life course, (g) providing conceptual and evidential standards for invoking personality types as opposed to personality dimensions, (h) addressing the psychophysiology of personality, and (i) focusing attention on psychological mechanisms as evolved dispositional strategies. PMID- 2198336 TI - Personality development in the evolutionary perspective. AB - A relationship between personality processes and evolution can be seen when behaviors associated with sexual maturation, mating, and parenting are examined. This article stipulates the types of proximal cues implicated in the shaping of personality variables that become important in the development of the individual's reproductive behavior. PMID- 2198337 TI - Is parent-offspring conflict sex-linked? Freudian and Darwinian models. AB - Freud's Oedipal theory sees parent-offspring conflict as a within-gender rivalry, whereas most modern evolutionary models interpret it as a gender-blind disagreement about resource allocation. New analyses of family homicides and a critical review of prior evidence do not support the central Freudian claim of a same-sex contingency in parent-offspring antagonism during the Oedipal phase. Several errors of fact and interpretation in psychoanalytic theorizing about family relations are discussed. We argue that psychoanalysts mistake substantive conflicts between nonrelatives for symbolic manifestations of family conflicts. PMID- 2198338 TI - On the universality of human nature and the uniqueness of the individual: the role of genetics and adaptation. AB - The concept of a universal human nature, based on a species-typical collection of complex psychological adaptations, is defended as valid, despite the existence of substantial genetic variation that makes each human genetically and biochemically unique. These apparently contradictory facts can be reconciled by considering that (a) complex adaptations necessarily require many genes to regulate their development, and (b) sexual recombination makes it improbable that all the necessary genes for a complex adaptation would be together at once in the same individual, if genes coding for complex adaptations varied substantially between individuals. Selection, interacting with sexual recombination, tends to impose relative uniformity at the functional level in complex adaptive designs, suggesting that most heritable psychological differences are not themselves likely to be complex psychological adaptations. Instead, they are mostly evolutionary by-products, such as concomitants of parasite-driven selection for biochemical individuality. An evolutionary approach to psychological variation reconceptualizes traits as either the output of species-typical, adaptively designed development and psychological mechanisms, or as the result of genetic noise creating perturbations in these mechanisms. PMID- 2198339 TI - Behavioral genetics and personality change. AB - Although research on personality and behavioral genetics has focused on the continuity of traits, both fields and their interface will profit from the consideration of trait change. In this article we review personality research on age differences in heritability and propose the counterintuitive hypothesis that, when developmental changes in heritability are found, heritability tends to increase. We also focus on behavioral genetic analyses of long-term developmental change. Research to date suggests that genetic involvement in adult personality change is slight whereas personality change in childhood is governed substantially be genetic factors. Finally, we consider a new topic, genetic influence on short-term change in personality. PMID- 2198340 TI - Biological bases of extraversion: psychophysiological evidence. AB - There is a good deal of evidence, particularly from electrodermal and electrocortical recording procedures, that introverts exhibit greater reactivity to sensory stimulation than extraverts. There is little evidence that introverts and extraverts differ in base level of arousal in neutral conditions, and there is no clear evidence that their differences in sensitivity to stimulation are determined by differences in attentional state. Faster auditory brainstem evoked response latencies observed for introverts implicate differences in peripheral sensory processes that are not determined by mechanisms in the reticular system as proposed in the arousal hypothesis. There is also evidence that individual differences in the expression of motor activity between introverts and extraverts involve differences in motoneuronal excitability. PMID- 2198341 TI - The psychophysiology of sensation seeking. AB - This article summarizes studies relating the trait of sensation seeking to electrodermal and heart-rate responses and cortical evoked potential arousal. Stimulus factors of novelty, intensity, and stimulus significance are important. High sensation seekers tend to give stronger physiological orienting responses than lows to novel stimuli of moderate intensity, particularly when such stimuli are of specific interest. Lows tend to show defensive responses as defined by heart-rate acceleration. The cortical reaction of the highs tends to be augmented by intense visual or auditory stimuli, while that of the lows tends to be reduced or unresponsive to variations in stimulus intensity. Differences between psychophysiological responses of high and low sensation seekers are interpreted as reflective of different evolved biological strategies for processing novel or intense stimulation. PMID- 2198342 TI - [Studies on quinolone antibacterials. I. Synthesis and antibacterial activity of 7-(2-aminoethoxy)-, 7-(2-aminoethylthio)-, and 7-(2-aminoethylamino)-1 cyclopropyl-6-fluoro-1,4-dihydro-4-oxo qui noline -3-carboxylic acids and their derivatives]. AB - 7-(2-Aminoethoxy)-, 7-(2-aminoethylthio)-, and 7-(2-aminoethylamino)-1 cyclopropyl-6-fluoro-1,4-dihydro-4-oxoq uin oline-3- carboxylic acids and their derivatives (11a--f, h, j, k, 12a--f, and 13a--f) were synthesized and their antibacterial activities were tested. Among them, compounds (13a, d) having a primary amino group at the terminal position of alkoxy and alkylthio groups were found to have excellent in vitro and in vivo antibacterial activity comparable to those of ciprofloxacin (5). Structure-activity relationship of these compounds was also stated. PMID- 2198343 TI - [Molecular mechanism of N4-aminocytidine mutagenesis]. AB - N4-Aminocytidine is strongly mutagenic towards E. coli, S. typhimurium, B. subtilis and coliphages phi X174 and M13mp2. It also causes mutations in mammalian cell lines and somatic cell mutations in D. melanogaster. The sequence analysis of deoxyribonucleic acid (DNA) from mutated phages revealed that N4 aminocytidine induces both adenine-thymine (AT) to guanine-cytosine (GC) and GC to AT transitions. No transversions are detectable. When E. coli and the mammalian cells were cultured in the presence of [3H]-N4-aminocytidine, [3H]-N4 aminodeoxycytidine was found in their DNA. It is likely that N4-aminocytidine is metabolized within the cells into N4-aminodeoxy-cytidine 5'-triphosphate (dCamTP), which is then incorporated into DNA, thereby causing base-pair transitions. To prove this hypothesis, we studied the incorporation of dCamTP into polynucleotides in the in vitro DNA synthesis catalyzed by E. coli DNA polymerase I large fragment (Klenow enzyme) and DNA polymerase alpha from a mouse cell line. Both polymerases catalyze incorporation of dCamTP into DNA efficiently in place of dCTP opposite guanine, and less efficiently, but to a significant extent, in place of dTTP opposite adenine. These observations prove the erroneous nature of dCamTP as a substrate for DNA synthesis. DNA containing N4 aminocytosine was prepared by the incorporation of dCamTP into single-stranded phage DNA annealed to complementary oligonucleotides. The DNA was transfected to E. coli cells. The analysis of progeny phages indicates that N4-aminocytosine residue in DNA causes A to G or G to A mutation in the position opposite to the site where N4-aminocytosine should be incorporated. PMID- 2198344 TI - Hepatitis. The forgotten disease. AB - Hepatitis is a significant disease process for health care professionals. Because of the large number of procedures performed by podiatrists in the course of patient care, they are at particular risk. The variants of hepatitis are reviewed, and the modes of transmission are discussed. Recommendations are made on protective measures to reduce contraction of this disease. PMID- 2198345 TI - Invited review: post-traumatic stress disorder; a new clinical entity? AB - Recently a spate of large scale disasters has caught public attention. Survivors of unexpected catastrophes find their lives radically changed. They may develop a characteristic pattern of symptoms in response to their exposure to overwhelming stress. Ten years ago, American psychiatrists introduced a new diagnostic category, post-traumatic stress disorder (PTSD), referring to the range of psychological symptoms survivors demonstrate after extreme trauma (Diagnostic and Statistical Manual of Mental Disorders, APA, Washington D.C.). Although the validity of this syndrome remains debatable, the term PTSD is increasingly in use, a practice likely to continue given its inclusion in the draft edition of ICD 10 (WHO, Geneva). This review looks at the evidence that PTSD describes a specific clinical entity. The historical background to the belief that individuals respond to stress is summarized. The criteria that must be fulfilled and methods of establishing a diagnosis are described. A discussion of aetiological factors and the natural history of the psychological response to stress follows, with reference to clinical management, including the provision of effective intervention for survivors to prevent a full blown stress reaction emerging. PMID- 2198346 TI - Case management: caring for psychiatric clients. PMID- 2198347 TI - The challenge of maternal phenylketonuria screening and treatment. AB - All newborn infants, male and female, have been screened for phenylketonuria (PKU) since 1961. Medical therapy is generally continued until age 6. The first cohort of treated females reached reproductive age 15 years ago, and new members are joining this cohort annually. This paper reviews the implications of childbearing in women who were treated for PKU as children and are no longer under treatment. Untreated maternal PKU can lead to mental retardation in utero. PMID- 2198348 TI - Amniotic fluid index measurement with the four-quadrant technique during pregnancy. AB - Eleven hundred thirty-four pregnant women with reliable dates underwent ultrasound evaluation for amniotic fluid index (AFI) measurement with the modified four-quadrant technique. We found that from 13 weeks' gestation the AFI rose progressively until 26 weeks. From then to 38 weeks the AFI measurements demonstrated little variation. After 38 weeks the AFI appeared to decline gradually. In the third trimester the mean AFI was 16.0 +/- 4.8 cm; 5% of cases had an AFI less than or equal to 8 cm, and 5% had an AFI greater than or equal to 24 cm. These results confirm the reproducibility of the semiquantitative technique and suggest that in estimating amniotic fluid volume, AFI measurement may be a more appropriate means than measurement of the single largest pocket or subjective assessment. Serial AFI measurement would be an effective way of assessing fetal status throughout pregnancy. PMID- 2198349 TI - The Pyridium pad test for diagnosing urinary incontinence. A comparative study of asymptomatic and incontinent women. AB - Eighteen women with urodynamically proven genuine stress incontinence awaiting surgery and 23 normal, asymptomatic, continent female volunteers took part in a study to compare the accuracy of a qualitative pad test with a quantitative pad weighing test in detecting urine loss. Each woman took 600 mg of phenazopyridine hydrochloride (Pyridium, Parke-Davis) in three equally divided doses over 18-24 hours and then underwent a standardized, one-hour pad test as described by the International Continence Society. The Pyridium pad test was regarded as positive if there was any orange staining on the pad. The quantitative pad-weighing test was considered positive if there was a weight gain of 1.0 g or more at the end of the one-hour test period. All 18 patients with genuine stress incontinence had positive Pyridium pad tests, and all had pad weight gains of greater than or equal to 1.0 g (mean, 16.5). The maximum pad weight gain in the asymptomatic, continent volunteers was 0.7 g (mean, 0.1), and none was aware of any urinary leakage during the test; however, 12 (52%) had positive Pyridium pad tests. The Pyridium pad test appears 100% sensitive in detecting urine loss in symptomatic women with genuine stress incontinence, but it has a high false-positive rate in healthy, asymptomatic, continent women. If pad-weighing tests are done, the addition of Pyridium generally will not be useful, and if Pyridium is used by itself, the results may be misleading. PMID- 2198350 TI - Nipple stimulation for labor augmentation. AB - A randomized, prospective study was undertaken to evaluate the efficacy of nipple stimulation with a breast pump as compared to oxytocin for augmentation of labor. The average and maximal uterine activity achieved was significantly higher in the oxytocin-stimulated group, without significant differences in the length of labor stages, cesarean section rate, Apgar scores or umbilical artery pH. Fifty percent of the patients failed to respond to nipple stimulation after 30 minutes and were switched to oxytocin. These patients experienced a more rapid rate of cervical dilation in the active phase and reached higher maximal uterine activity with oxytocin stimulation; however, the cesarean section rate was highest in this group. Nipple stimulation with a breast pump appears to be a safe and effective alternative to oxytocin for the augmentation of labor. PMID- 2198351 TI - Intrapartum amniotic fluid volume at term. Association of ruptured membranes, oligohydramnios and increased fetal risk. AB - The amniotic fluid index (AFI), a semiquantitative technique for assessing amniotic fluid volume, has been shown to be a useful adjunct in antepartum surveillance. We evaluated the usefulness of the AFI in the early intrapartum period as it relates to subsequent fetal morbidity and fetal heart rate patterns. Two hundred term gravidas presenting in the latent phase of labor with vertex presenting fetuses were studied. An intrapartum AFI less than or equal to 5.0 cm was associated with a significant increase in the risk of cesarean section for fetal distress and of an Apgar score of less than 7 at one minute as well as abnormal fetal heart rate patterns in late labor. The majority (71.4%) of the patients with an intrapartum AFI less than or equal to 5.0 cm had ruptured membranes on entry; however, there was no significant difference in outcome when they were compared to patients with intact membranes and oligohydramnios. Variable decelerations on entry were associated with oligohydramnios in 43.8% of the patients. An AFI less than or equal to 5.0 cm in the early intrapartum period is a risk factor for perinatal morbidity and abnormal fetal heart rate patterns in subsequent labor, and ruptured membranes in early labor are a risk factor for oligohydramnios. PMID- 2198352 TI - Synovial fluid tests. What should be ordered? AB - To determine which synovial fluid tests are most useful, we prospectively analyzed the synovial fluid test results of 100 consecutive patients undergoing diagnostic arthrocentesis. Each patient's diagnosis was established independently of synovial fluid laboratory test results; in 69 patients a definite inflammatory or noninflammatory categorization could be made. Sensitivity and specificity were estimated for synovial fluid white blood cell count (sensitivity, 0.84; specificity, 0.84), percentage of polymorphonuclear cells (sensitivity, 0.75; specificity, 0.92), glucose (sensitivity, 0.20; specificity, 0.84), protein (sensitivity, 0.52; specificity, 0.56), and lactate dehydrogenase (sensitivity, 0.83; specificity 0.71). Receiver operating characteristic regression analysis indicated that both white blood cell count and percentage of polymorphonuclear cells were found to contribute independent diagnostic information but lactate dehydrogenase did not. In a separate, retrospective analysis of 19 patients with definite septic arthritis, similar results were observed. We conclude that synovial fluid white blood cell count and percentage of polymorphonuclear cells perform well as discriminators between inflammatory and noninflammatory disease. Ordering chemistry studies of synovial fluid should be discouraged because they are likely to provide misleading or redundant information. PMID- 2198353 TI - Treatment of hypertension in the elderly. AB - Hypertension, both combined diastolic plus systolic and isolated systolic, is common in the elderly. Elderly hypertensive patients pose a number of diagnostic dilemmas, including pseudohypertension, postural and postprandial decreases in blood pressure, and the potential for renovascular hypertension. Data from large clinical trials have documented protection from cardiovascular complications by antihypertensive therapy for elderly people with combined systolic and diastolic hypertension. However, no data are available concerning the value of therapy for those with isolated systolic hypertension. Until such data become available from the Systolic Hypertension in the Elderly Program in 1991, cautious reduction of elevated systolic blood pressure levels is recommended. The fragile physiologic characteristics of the elderly demand caution and gentleness in the use of any therapy to lower blood pressure. Nondrug therapies are safe and may be effective. A variety of drugs are available and can be used to gradually reduce blood pressure to presumably safer levels. PMID- 2198354 TI - Beyond 'abortion': RU-486 and the needs of the crisis constituency. PMID- 2198355 TI - [Regional distribution and function of brain renin angiotensin system]. PMID- 2198356 TI - [Mechanism of generating neuropeptide family--selective regulation of gene transcription and processing enzyme]. PMID- 2198357 TI - [The effect of partial hepatectomy on glucose-stimulated insulin release from the isolated perfused pancreas in rats]. AB - To investigate the functional changes of endocrine pancreas in the early stage after partial hepatectomy, we evaluated the changes in the secretion of insulin to glucose load in perfused rat pancreas at 4 and 7 days after about 70% hepatectomy. Insulin responses to glucose load were significantly augmented at 4 days compared with both the normal and sham-operation rats and at 7 days also significantly augmented compared with the normal rats. These results are in accordance with the morphological changes of islet and indicate that in the early stage after hepatectomy, the response of islet B-cells to glucose load are increased in order to support the glucose metabolism in this stage. Thus, insulin seems to play an important role in the regenerating liver after hepatectomy and these changes seem to be one of the adaptation of endocrine pancreas after hepatectomy to support the regenerating liver. PMID- 2198358 TI - [A case of progressive systemic sclerosis associated with pseudo-obstruction]. PMID- 2198359 TI - [A case report of true enterolith (bile acid) with gastrointestinal bleeding, hypoproteinemia and subacute ileus--reference to reported 13 cases in Japan]. PMID- 2198360 TI - [A case of liver cystadenoma--significance of tumor marker level of the cyst fluid in differentiating pathological nature]. PMID- 2198361 TI - [Portal hemodynamic changes from partial hepatectomy--quantitative analysis of portal flow before, during and after hepatectomy, using an Doppler ultrasound system]. AB - We investigated portal hemodynamic changes in 86 patients with hepatic tumors who underwent partial hepatectomy. Portal blood flow was measured using a sector type Doppler ultrasound system before, during and after operation. In the intraoperative studies, the portal flow in patients who underwent massive liver resection decreased significantly. On the other hand, the portal flow in patients with minor liver resection tended to increase, but not significantly. Overall, portal flow per unit of cardiac out put decreased significantly; it also decreased significantly in patients who underwent massive or major liver resection, in patients with liver cirrhosis, and in patients whose post operative clinical course was satisfactory. In the post-operative studies (10-12 days after surgery), the portal blood flow decreased significantly in patients who manifested a severe post-operative clinical course; it showed no significant change in other patients. It is thus essential to monitor the portal hemodynamics of partial-hepatectomy patients. This is most readily realized using Doppler ultrasound. PMID- 2198362 TI - [Study of the changes in glomerular antigenicity in various renal diseases with anti-human renal monoclonal antibodies]. AB - We produced 22 different kinds of monoclonal antibody (Mab) by immunizing mice with human GBM antigens. In these Mabs, Mab-G1 to G5 recognized only GBM in the glomerulus, Mab-E1 and E2 recognized only glomerular epithelial cells, and Mab-M1 to M4 recognized mainly mesangium. The reactions of these Mabs with known GBM antigens such as type IV collagen, fibronectin and laminin were negative by immunoblotting. Using Mab-G1, Mab-E1 and Mab-M1, changes in the antigenicity of antigens recognized by Mabs were examined on kidney sections from the patients with various renal diseases by the indirect immunofluorescence test. When Mab-G1 recognizing GBM was used, there was no particular change of antigenicity in minimal change nephrotic syndrome (MCNS) and IgA nephropathy (IgA), whereas in membranous nephropathy (MN) thickened GBM was found to maintain antigenicity and the region of deposits was observed as negative punched-out region. In type I and III of membranoproliferative glomerulonephritis (MPGN), GBM was observed only outside of subendothelial deposits without showing double contour. In type II MPGN, GBM showed a double linear pattern and antigenicity of GBM in regions of dense deposits was not detected. When Mab-E1 recognizing glomerular epithelial cells was used, there was no change of antigenicity in the renal diseases. Further, in crescentic glomerulonephritis, the region of the cellular crescents was not stained. When Mab-M1 recognizing mesangium was used, extensive staining was observed in the increased mesangium in IgA, MPGN, and diabetic nephropathy. We feel that it is of significance in elucidating the pathogenesis of renal diseases to study the changes of glomerular antigenicity in diseased kidneys by using anti-human renal monoclonal antibodies. PMID- 2198363 TI - [Studies on the intraglomerular distribution of fibronectin in IgA nephropathy- in relation to clinical pictures and prognosis]. AB - Forty-seven patients with IgA nephropathy were classified as having mesangial pattern (M: 29 cases) or mesangiocapillary pattern (C: 18 cases) according to an intraglomerular distribution of fibronectin (FN) observed by the immunofluorescence (IF) technique. The relationships between these IF patterns and the clinical pictures, and that between these IF patterns and prognosis of the disease were investigated. Significantly higher diastolic blood pressure, proteinuria, serum creatinine (Cr), total cholesterol and IgA, and lower total protein were noted in C pattern as compared with M pattern. beta-thromboglobulin, fibrinogen (Fib) and platelet factor 4 were found to be significantly higher in C pattern. Platelet aggregation (ADP 1 microM/ml) and FN tended to increase (p less than 0.1) as well. The distribution of FN in the glomeruli was similar to those of IgA and Fib, although perfect agreement was not observed. The picture in which FN might be infiltrated into the endothelial side of the glomerular basement membrane from the mesangium was observed in C pattern by the immunoelectron microscopic study. In the follow-up study, proteinuria showed a tendency to decrease in M pattern. On the other hand no marked change was observed in C pattern. C pattern showed high serum Cr levels throughout the course of the study as compared with M pattern. A significantly greater number of C pattern cases had serum Cr of 2 mg/dl or higher, C pattern showed a significant decrease of 1/Cr over time as compared with M pattern. Higher serum Fib and FN, platelet aggregation (ADP 1 microM/ml), antithrombin III and plasminogen were observed in C pattern as compared with M pattern. These results suggest that an involvement of tissue FN, especially the existence of FN in the capillary loop, may be an aggravating factor of IgA nephropathy, in addition to an augmented platelets blood coagulation mechanisms. Therefore, it may be possible to evaluate the prognosis of IgA nephropathy by FN deposit patterns. PMID- 2198364 TI - [A new automated renal biopsy technique under ultrasound guidance]. AB - We evaluated a new automated biopsy device for percutaneous renal biopsies under ultrasound guidance, which was recently introduced in Japan for prostate biopsies. This device (Biopty-Gun: Bard Biopty Instrument Uppsala, Sweden) employs a Tru-Cut type smaller needle (18 gauge). We were able to obtain one or two renal tissues in all 57 cases with great ease and in little time. The length of specimen was sufficient (5-17 mm), but the width was thinner than the samples with the Vim-Silverman or Tru-Cut needles. We could achieve a definitive pathological diagnosis in 54 of 57 cases (94.7%), but now, we try to obtain two pieces of tissue for taking more adequate tissue. Only three patients had perirenal hematomas noted by computerized tomography or ultrasonography. We believe that this new automated technique offers a safer and more effective means of obtaining renal tissue. PMID- 2198365 TI - [Serum beta 2-microglobulin concentration and its removal in patients treated with continuous ambulatory peritoneal dialysis]. AB - This study was performed to clarify serum beta-2 microglobulin (beta 2-M) level and its change in 50 CAPD and 56 HD patients. There was significant correlation between duration of dialysis and serum beta 2-M level in CAPD and HD patients treated under 12 months, but no correlation in those treated over 12 months. Serum beta 2-M level was 33.5 +/- 9.1 mg/l in 45 CAPD patients treated over 12 months, and 46.2 +/- 21.1 mg/l in 35 HD patients. In 26 CAPD patients treated over 12 months, clearance and removal of beta 2-M were 1.0 +/- 0.3 ml/min and 43.0 +/- 17.8 mg/day. There was significant correlation between dwell time and beta 2-M removal (p less than 0.01), and these results suggested beta 2-M was removed by diffusion. Because CAPD treatment can lower serum beta 2-M level compared to HD, there is possibility that CAPD is useful at prevention of dialysis associated amyloidosis. PMID- 2198366 TI - [Effect of renin inhibitor (ES-1005) on expression of the kidney renin gene in sodium-depleted marmosets]. AB - Effect of renin inhibitor ES-1005 or captopril on the renin synthesis by the kidney was investigated in sodium-depleted marmosets. The level of kidney renin mRNA was measured after 2-hour (acute study) and one-week (chronic study) administrations of the two agents. Relative amounts of kidney renin mRNA were measured by densitometric Northern blot analysis using an alpha-32P-labelled human renin cDNA fragment as a hybridization probe. In the acute study, treatment with captopril significantly increased plasma renin activity (PRA) (p less than 0.05), but did not change the level of kidney renin mRNA. In the chronic study, treatment with captopril markedly increased PRA as well as the level of kidney renin mRNA (4.7-fold and 6.3-fold increases, respectively). In contrast, treatment with ES-1005 completely inhibited PRA and significantly suppressed the level of kidney renin mRNA in both acute and chronic studies (about one-third of the normal control, p less than 0.05). These results suggest that renin inhibitor ES-1005 not only inhibits plasma renin activity but also suppresses the synthesis of renin by the kidney. PMID- 2198367 TI - [Evaluation of image quality and lesion detectability on I-123 IMP brain SPECT]. AB - Influence of image quality on lesion detectability in I-123 IMP brain SPECT was discussed in forty-two cases with various cerebrovascular disorders. Fifty nine lesions, which were considered to show decreased uptake of I-123 IMP, were analyzed in this study. In all cases, SPECT examinations were started within 30 minutes after intravenous administration of 3 mCi of I-123 IMP. To determine the lesion detectability, fourteen radiologists from nine hospitals were gathered and film reading was carried out. To classify the image quality into valuable or not, findings of five points on SPECT image were visually evaluated; 1) uniformity of cortex accumulation, 2) separation of bilateral visual cortices, 3) density of white matter, 4) separation between basal ganglion and thalamus, 5) density of basal ganglion and thalamus. Mean lesion detections were 10.3/14 for the lesions of cerebral cortex, 9 for cerebellum, 3.58 for white matter and 3.22 for basal ganglion and thalamus, respectively. The detectability was certainly influenced by the image quality in the lesion of basal ganglion and thalamus, white matter and single lobe of cerebral cortex. We concluded that detection of small lesions and deep lesions with I-123 IMP SPECT was dependent on the image quality and the proposed classification of I-123 IMP SPECT image was useful for evaluating image quality from the points of view of the lesion detectability. PMID- 2198369 TI - [Captopril-enhanced renography using 99mTc-DTPA in renovascular hypertensive patients]. AB - Dynamic renal scintigraphy with 99mTc-DTPA before (baseline renography: BS-RG) and 1 hour after administration of 25 mg to 50 mg of captopril (captopril enhanced renography: CP-RG) was performed in a selected series of 18 patients suspected of having renovascular hypertension. Final diagnosis was made by angiography and further clinical follow-up. Eight patients were considered as renovascular hypertension (RVH), 6 with bilateral renal artery stenosis (BRAS) and 2 with unilateral renal artery stenosis (URAS). The remaining 10 patients were non-renovascular (non-RVH). Two criteria were prospectively employed for evaluating positive response induced by captopril. Glomerular filtration rate (GFR) on BS-RG (GFRbase) and on CP-RG (GFRcap) was estimated by early (120-180 seconds) DTPA uptake by the kidney, and then captopril response rate (CRR) was calculated in the following: CRR = (GFRcap-GFRbase)/GFRbase X 100 (%). CP-RG was considered positive when it was less than 20%. Renogram shape was also independently evaluated. CP-RG was also considered positive when either a delay of time to peak activity of more than 5 min or conversion of renogram shape to an obstructive or non-functioning pattern was observed. The sensitivity and specificity of CRR and change in renogram were 50% and 80%, 63% and 100%, respectively. In BRAS, positive response was observed in the unilateral kidney alone which maintained relatively a good renal function. CP-RG could not differentiate RVH with URAS from that with BRAS. Four patients were followed after the surgical or angioplastic treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198368 TI - [Clinical evaluation of immunoscintigraphy with 131I anti-CEA and 131I anti-CA 19 9 monoclonal antibody cocktail (IMACIS-1)--report of the phase II study]. AB - The clinical trials of immunoscintigraphy with a cocktail of 131I anti CEA monoclonal antibody F(ab')2 and 131I anti CA 19-9 monoclonal antibody F(ab')2 (IMACIS-1) were performed to evaluate the safety and clinical usefulness. Thirty five patients with proven cancer in six hospitals were examined in the phase two study. No significant changes of the heart rates, temperature, blood pressure, respiratory rates and clinical laboratory data were observed after i.v. IMACIS-1. Significant elevation of HAMA and IgE values in serum were not shown. Positive scintigrams which were interpreted by each hospital were obtained in 31/35 (89%) patients and in 39/53 (74%) lesions. The safety and clinical usefulness of immunoscintigraphy with IMACIS-1 were proven in the phase two study. PMID- 2198370 TI - [Adrenal surgery]. AB - In adrenal surgery, of note are increase of the incidence of incidentaloma because of a rapid advance of various image diagnostic procedures, change of the approach of choice due to the more accurate preoperative localization of the adrenal lesions, and the treatment of bilateral lesions. Additionally, the treatments of adrenocortical carcinoma and malignant pheochromocytoma and the method of cortisol withdrawal in Cushing's syndrome were reviewed and discussed. It is important for urologists to perform adrenal surgery appropriately by preoperatively elucidating the full picture of adrenal disorder. PMID- 2198371 TI - [Renal cell carcinomas. Clinical studies on diagnostic opportunities]. AB - We clinically investigated 150 subjects suffering from renal cellular cancers as to their diagnostic opportunities. They underwent medical treatment after being hospitalized in the urology section of Gunma University from 1961 to 1988. We divided the cases into two groups to be compared: 63 cases in the first period (1961 to 1979) before introduction of ultrasound (US) and scan (CT), and 87 cases in the second period (1980 to 1988) after introduction of the above devices. The number of patients increased in the second period, year by year. Evaluation of symptoms indicated that 62 of the 63 cases in the first period belonged to the suspected category; the remaining one (1.6%) belonged to the incidental category, but its diagnosis followed intravenous pyelography (IVP). Out of the 87 cases in the second period, 29 (33.3%) belonged to the incidental category which was recognized to be increasing; 19 cases were diagnosed based on US findings, and 6 cases on CT. Concerning prognosis, a significantly favorable prognosis was indicated for the second-period cases as compared with those of the first period, from the statistical point of view. With respect to progressive degree and prognosis of 58 suspected cases and 29 incidental cases in the second period, statistically there were significantly more cases of low grade and, therefore, with favorable prognosis in the latter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198372 TI - [Localizing methods of primary hyperparathyroidism and those results]. AB - The results of several pre-operative localizing methods and pathological findings were compared in 11 patients with primary hyperparathyroidism. 1. The accuracy rate was highest with selective blood sampling from the thyroid vein and MRI, which was 75% with both methods. The 3rd was dual photon scintigraphy, the accuracy rate being 62.5%. The 4th was ultrasonography, 57.1%, and the rate was lowest with CT, 25%. 2. MRI-a new localizing method-has a weak point that it cannot differentiate lymph nodes from parathyroid adenoma/hyperplasia. 3. Not to overlook small lesion of primary hyperplasia, several localizing methods should be performed before initial neck exploration. PMID- 2198373 TI - [An experience of single dose captopril renal scintigraphy in the diagnosis and management of bilateral renovascular hypertension]. AB - A 41-year-old woman visited our hospital with chief complaint of hypertension which was refractory to multiple antihypertensive drugs. Her blood pressure was 200/140 mmHg and her plasma renin activity was as high as 3.1 ng/ml/hr. Angiography revealed bilateral renal artery stenosis. To determine the laterality of the kidney which were responsible for her hypertension, the 99mTc-DTPA renal scintigraphy with captopril was performed. The estimated GFR of the right kidney was lowered than that of the control, while there was no change in the left kidney. Subsequently Percutaneous Transluminal Angioplasty (PTA) was performed to the right kidney. Postoperatively blood pressure remained elevated as well as serum renin level. 99mTc-DTPA scintigraphy with captopril was repeated and revealed no decrease in the GFR of the right kidney this time, but significant reduction in the GFR of the left kidney. After the second PTA to the left kidney, her blood pressure was finally normalized. Postoperatively GFR of both kidneys was not affected by captopril on renal scintigraphy, and currently she has remained normotensive without medication. 99mTc-DTPA scintigraphy with captopril appears to be a useful method to diagnose the laterality and to evaluate in clinical response to therapeutic intervention. PMID- 2198374 TI - [Serological diagnosis of pulmonary aspergillosis--measurement of IgG-, IgM- and IgA- antibodies against Aspergillus fumigatus by means of ELISA]. AB - Serological diagnosis plays an important role in the diagnosis of pulmonary aspergillosis, however, precipitation-in-gel test is neither sensitive nor quantitative. Recently, several investigators have used the ELISA technique for the detection of antibodies against Aspergillus fumigatus and reported the usefulness of this method. In this report, we measured IgG-, IgM-, and IgA- antibody titers against Aspergillus fumigatus by means of ELISA in sera from patients with several different lung diseases including pulmonary aspergillosis. The results obtained were as follows: 1) Measurement of IgG-antibody titers was most useful for the diagnosis of pulmonary aspergillosis. 2) Measurement of IgG antibody titers was more sensitive than precipitation-in-gel test. 3) IgG antibody titer was quantitative and reflected the clinical course of pulmonary aspergillosis. PMID- 2198375 TI - [Effect and correlation of various risk factors in the development of retinopathy of prematurity. A retrospective study of 338 premature infants]. AB - The statistical significance of ophthalmological and pediatric findings in the development of retinopathy of prematurity (ROP) was evaluated in a retrospective study of 338 premature infants. Short gestation time, frequent hypoxia, and low birthweight were strongly correlated with advanced stages of ROP. The influence of Vitamin E treatment, duration of oxygen therapy, and need for transfusions was less significant. Neither multiple births nor the infant's sex had any influence on the development of ROP. Cryotherapy appears to reduce ROP, but the number of cases in the present study was too small to permit statistical analysis. PMID- 2198376 TI - [Iritis following cataract operations. Historical retrospective with critical comments on a so-called "toxic lens" syndrome]. AB - Postoperative inflammation is one of the oldest complications of cataract surgery. It was described by the Indian Susruta as early as 500 BC. Following the introduction of cataract extraction by Daviel in 1745, these operations attracted increasing interest. In 1786 de Wenzel distinguished two types of postoperative inflammation. In the dangerous type there was involvement of the entire eye and severe pain; in the benign type, which began in the first few postoperative days, the conjunctiva and lids were not involved, and even if hypopyon developed there was no severe pain. During the 19th century, the possible causes of the benign type of iritis were discussed, including infection, phacoanaphylaxis, trauma, toxicity of irrigation solutions etc. In the early days of implantation of intraocular lenses, from 1949 onward, postoperative inflammation was common. However, it was not until 1980 that the term "toxic lens syndrome" was introduced. The clinical descriptions do not differ much from other descriptions of benign iritis published during the last 200 years. Therefore, it does not seem that there is any great advantage to be gained by using this new term. PMID- 2198377 TI - Refractory and relapsing Hodgkin's disease: role of high-dose chemotherapy with bone marrow transplantation. AB - Thirty percent of adult patients with Hodgkin's disease fail primary treatment or relapse after treatment. Whereas overall mortality for Hodgkin's disease is about 20%, half the patients who relapse will die. Among patients with refractory or relapsing disease, about a third can be rescued by conventional salvage treatment. Unfortunately, except for patients with late relapse, remission after conventional salvage treatment is generally not of long duration. However, durable complete remissions can now be achieved in nearly a third of patients with refractory or relapsing disease by means of very aggressive (myeloablative) chemotherapy with consecutive autologous bone marrow transplantation (aBMT). The rate of durable complete remissions seems to be even higher if previous exposure to chemotherapeutic agents is not in excess of two different treatment protocols (optimal timing of aBMT) and if responsiveness to cytotoxic drugs is preserved (low degree of drug resistance). Bone marrow transplantation should be restricted to patients whose resulting long-term prognosis justifies such radical treatment. Reflecting ongoing clinical therapy-studies, in particular in Germany, the role of bone marrow transplantation in a general concept of salvage treatment should be pointed out. Patients should be considered candidates if they fail alternating primary chemotherapy or develop an early relapse after this treatment, but still show responsiveness to chemotherapeutic agents. PMID- 2198378 TI - Prediction of diuretic mobilization of cirrhotic ascites by pretreatment fractional sodium excretion. AB - In a randomized prospective study the efficacy and side effects of xipamide versus the combination spironolactone/furosemide in the treatment of cirrhotic ascites were studied. Out of 27 patients four responded to a basic treatment consisting of salt and water restriction and one had to be excluded because of deterioration of kidney function. The remaining 22 patients were randomized to additional treatment with either 20 mg xipamide/day (group I) or 200 mg spironolactone/day combined with 40 mg of furosemide every other day (group II). A response to treatment during the first 4 days was seen in 7 of 11 patients of group I versus only 3 of 11 patients in group II. In the latter group 7 of 11 patients finally responded after 8 days of treatment. Responsiveness to either diuretic treatment strongly depended on pretreatment fractional Na excretion, FENa. The resistance to diuretic treatment can be predicted by a FENa less than 0.2%, and could be overcome by additional strategies known to reduce avid proximal Na reabsorption. Xipamide frequently induced hypokalemia, whereas hyperkalemia was seen following treatment with spironolactone/furosemide. Kidney function remained stable during either diuretic treatment. PMID- 2198379 TI - [Experiences with the use of an intravascular 6 French endosonography catheter in vivo]. AB - Further progress in intraluminal sonography has led to the development of a 6 French ultrasound imaging catheter. This report demonstrates in vivo results using this new technique in a swine. Intraluminal echographic images obtained from the aorta and iliac arteries were of good quality. Artifacts such as image distortion were related to the 20 Mhz mechanically rotating tip motion and caused a loss of image quality. Atherosclerotic lesions could be visualized. The characteristics of the echo image of an atherosclerotic lesion related to the composition of corresponding histological sections of the lesion. Intraluminal sonography may develop into a new diagnostic tool, further enhancing progress in atherosclerosis research and improving the evaluation of coronary arteries and perivascular structures. Combined use with balloon angioplasty might also improve invasive therapeutic procedures. PMID- 2198380 TI - Acromegaly and hypertension: prevalence and relationship to the renin-angiotensin aldosterone system. AB - The prevalence of arterial hypertension was evaluated in a retrospective study of 158 patients with acromegaly, and results were compared to control populations, namely, the Munich Blood Pressure Study (MBPS) and the Framingham Study. The prevalence of hypertension (defined according to WHO criteria) was significantly increased in female patients but not in men; hypertensive acromegalics were older and tended to have higher body weight compared to normotensive patients. Hypertension was not related to serum concentrations of growth hormone. After successful treatment of acromegaly, growth hormone levels and systolic and diastolic blood pressure fell only in female hypertensive acromegalics; this did not occur in normotensives. The rise in plasma renin activity in response to upright posture was diminished in 57.9% of acromegalic patients. The prevalence of low-renin hypertension in our group of patients was 31.6%, which is similar to figures reported for unselected non-acromegalic subjects with essential hypertension. Orthostatic renin activity was weakly and inversely related (r = 0.3) to blood pressure. No relationship between plasma aldosterone concentration and blood pressure could be detected; however, in acromegalic women, aldosterone rose higher after ambulation than in men. In conclusion, hypertension is a common problem in acromegaly and at least in part related to similar risk factors in control populations. The association with abnormalities of the renin-angiotensin aldosterone system is difficult to interpret and does not offer an explanation for the slight increase in the prevalence of hypertension. PMID- 2198381 TI - [Effect of cisapride on esophageal motility in healthy probands and patients with progressive systemic scleroderma]. AB - Prokinetic agents might be useful in patients with progressive systemic sclerosis (PSS) who have disturbed function of the lower esophageal sphincter and impaired acid-clearance of the tubular esophagus. We therefore compared, by means of esophageal manometry, the effect of 20 mg cisapride orally vs. placebo in 12 patients with progressive systemic sclerosis and proven esophageal dysfunction as well as in 10 healthy volunteers in a double-blind, prospective trial. An increase of the lower esophageal resting pressure from 18.1 +/- 2.4 mm Hg to 23.9 +/- 8.1 mm Hg* after cisapride administration was observed in healthy volunteers, and from 10.9 +/- 3.2 mm Hg to 13.6 +/- 4.0 mm Hg* in the PSS patients. The amplitudes of peristaltic waves in the distal part of the esophagus were increased by cisapride from 83.8 +/- 10.6 mm Hg to 95.6 +/- 15.5 mm Hg* in volunteers and from 28.9 +/- 12.8 mm Hg to 36.8 +/- 16.2 mm Hg in patients (*:P less than 0.05). These results indicate that cisapride has a therapeutic rationale in the treatment of esophageal dysfunction in PSS; further clinical investigations are justified. PMID- 2198382 TI - Newer aspects of drug therapy in the elderly. PMID- 2198383 TI - [Pathophysiology of various forms of hyperthyroidism]. PMID- 2198384 TI - [Differential diagnosis in hyperthyroid metabolic status]. PMID- 2198386 TI - [Severe courses of hyperthyroidism up to a thyrotoxic crisis]. PMID- 2198385 TI - [Therapy of thyroid gland autonomy]. PMID- 2198387 TI - Drugs in autoimmune diseases. AB - Autoimmune diseases arise when autoimmunity or the loss of self tolerance results in tissue damages. Many mechanisms have been proposed for the origin of autoimmunity, including immunologic, viral, hormonal and genetic factors. All known parts of the immunological network are involved in causing immunopathologic symptoms. Therefore, more or less specific immunosuppressants are widely used in the treatment of autoimmune disorders which range from organ-specific, i.e. Hashimoto's thyroiditis, to non-organ-specific or systemic diseases, i.e. systemic lupus erythematosus. Unspecifically acting cytostatics do not only suppress autoimmune reactions but also create severe side-effects due to the impairment of immune responses against foreign antigens, leading, for example, to an increased risk of infections. Moreover, the genotoxic activity of cytostatics might induce malignancies. Corticosteroids are clinically well known and very active agents for the management of acute symptoms but different side-effects limit their use in the treatment of chronic diseases. Cyclosporin A has been an important step forward to a more specific prevention of organ transplant rejections and to the therapy of some autoimmune disorders. Modern approaches to immunosuppression include monoclonal antibodies directed against a variety of different determinants on immunocompetent cells. Ciamexone and Leflunomide which are in early clinical and preclinical development, respectively, might be interesting new drugs. Future immunopharmacologic drug research and development should lead to more specific, low molecular weight, orally active and chemically defined immunosuppressive compounds with good tolerability under long-term treatment of autoimmune diseases. PMID- 2198388 TI - On the pathogenesis of type 1 (insulin-dependent) diabetes mellitus: facts, areas still under development and new perspectives. AB - The observations emerged from the pancreatic transplant experiments in identical twins indicate that Type I diabetic patients maintain memory cytotoxic T cells for several years and these can be "re-awakened" when Class I identical beta cells are re-introduced into the diabetic melieu. In addition, these data have shown that these lymphocytes can (in a matter of a few weeks) cause rapid irreversible decompensation of beta cell function. From this, an important lesson is learnt: cytotoxic T cells, when generated in sufficient number against beta cells do not leave much "breathing space" for these cells. This has important implications for explaining the long latency period preceding the acute onset of Type I diabetes. ICA, when produced, seem unable to cause gross damage to beta cells. They persist for several years in the blood, but beta cell function remains apparently unaltered. It is only when cytotoxic T cells, with fine specificity for beta cells are generated that the 'killing cycle' is completed. Whether these cells are present all the time, and kept under tight control by active suppressor mechanisms or whether they appear only after an environmental trigger (e.g., retroviruses) is unknown. If the former is the case, this would give strong support to the suggested important role of suppressor T cells in the pathogenetic circuit. Some evidence for this has been produced (rev. in [116]) but, obviously, it requires confirmation (see debate which followed [116]). If, on the other hand, the latter is experimentally confirmed, one can return to the theory that cytotoxic T cells acquire the characteristics of autoreactivity by expressing receptors on their surface in a configuration which enables combination with self-autoantigens (rev. in [45]). In summary, the study of the etiopathogenesis of Type I diabetes and human autoimmunity in general has attracted a great deal of interest among immunologists. It is only by further dissecting the various limbs of the undesirable immune response against beta cells and, by trying to formulate novel hypotheses, sometimes against accepted dogmas [32], that the complete picture will be finally disclosed. At this stage it will be possible to design effective therapy trials, so that Type I diabetes and other related autoimmune disorders ultimately may be prevented. PMID- 2198389 TI - Specific therapeutic attempts in experimental and clinical type-I diabetes. AB - The morphological basis of type-I diabetes is the destruction of the islets of Langerhans by an inflammatory process. Immunosuppressive and immunomodulatory mechanisms can prevent diabetes in NOD-mice and BB-rats when given before onset of the disease. In man at the time of diagnosis of diabetes insulitis has progressed already to a loss of more than 80% of the Beta-cells. Several immunosuppressive drugs and immunobiological regimen may influence the course of the disease only in the sense of a temporary remission. Cyclosporine-A was the most effective drug, but can not be recommended for general use at present time because of side effects on the kidney at least when given in higher doses. Whether minimizing the effective dose will be equally effective remains open. Other drugs as ciamexone which seems to be safer have to be taken into account for further studies. Suppression of insulitis most probably will be more successful when the treatment starts at an earlier phase i.e. before onset of the disease. The criteria at what time this may be justified have to be elaborated. PMID- 2198390 TI - Diagnostic, prognostic and therapeutic aspects of systemic lupus erythematosus and rheumatoid arthritis. AB - Rheumatoid arthritis and systemic lupus erythematosus are rheumatic diseases characterized by excessive immunoreactivity. Exaggerated immunity is manifested as auto-antibody production and aberrant cell-mediated reactions directed against autologous tissue. Although the mechanisms and site for abnormal immune responses are not completely understood, risk factors that predispose an individual to develop rheumatoid arthritis or systemic lupus erythematosus can be defined. Genetic factors, especially HLA genes, play an important role in rendering a host susceptible to the sequelae of immunologically mediated diseases. Modern technology, such as T-cell cloning, can be used to dissect polymorphic HLA determinants involved in the genetic susceptibility for rheumatoid arthritis and systemic lupus erythematosus. Mapping of disease-associated determinants in rheumatoid arthritis patients suggests that polymorphic sites within the third hypervariable region of the HLA-DR beta 1-chain are functionally involved in the initiation and perpetuation of the disease. These HLA-determinants function to mediate the contact between the HLA- and the T-cell receptor molecules. In systemic lupus erythematosus patients, the role of disease associated molecules appears to be distinct; genetic susceptibility is correlated to patterns of auto antibody productions. Immunogenetic studies may provide diagnostic tools to subset patients with rheumatoid arthritis and systemic lupus erythematosus and develop prognostic markers to tailor immunomodulatory therapy. Both diseases are characterized by high levels of morbidity and mortality, but can now be mitigated by the careful and judicious use of immunosuppressives. PMID- 2198391 TI - [Learning by computer]. PMID- 2198392 TI - Determination of diastolic function by radionuclide ventriculography. AB - Diastolic filling can be measured by radionuclide ventriculography with use of several techniques including those based on gated and list-mode acquisitions, the first-pass method, and the nuclear probe. Radionuclide ventriculography specifically assesses volumes, rates of volume change, and intervals during ventricular filling. Normal values for diastolic filling measurement vary depending on the individual radionuclide methods used and the age of the patient. Comparative studies of the radionuclide method with contrast angiographic and Doppler echocardiographic techniques for measuring diastole are discussed, and the advantages and disadvantages of the radionuclide techniques are explored. The role of radionuclide assessment of diastolic function in specific clinical examples of hypertrophic cardiomyopathy, hypertension, anthracycline-induced cardiomyopathy, and coronary artery disease is reviewed. Radionuclide ventriculography is an accurate and easily applicable procedure for studying left ventricular volume changes in diastole. PMID- 2198393 TI - Hepatic cysts in autosomal dominant polycystic kidney disease. AB - Hepatic cysts are one of several extrarenal manifestations of the ADPKD gene. Several factors, including age, gender, pregnancy, the degree of renal cystic disease, and the extent of renal functional impairment, may modify the expression of hepatic cystic disease. With advances in medical care, such as improvement in the management of end-stage renal disease, hemodialysis, and renal transplantation, patients with ADPKD will experience an increased life expectancy. As a result, complications associated with hepatic cysts may become more common, and physicians may encounter an increasing number of patients with ADPKD who have infected hepatic cysts. Several issues in the management of this complication remain unresolved, but the article by Telenti and associates in this issue of the Proceedings addresses some of the critical issues that physicians who are responsible for the care of these patients will certainly confront in future years. PMID- 2198394 TI - Decision analysis for management of solitary pulmonary nodules. PMID- 2198395 TI - Dr. William J. Mayo and the University of Michigan. PMID- 2198396 TI - Hepatic cyst infection in autosomal dominant polycystic kidney disease. AB - To characterize the syndrome of hepatic cyst infection in autosomal dominant polycystic kidney disease (ADPKD) and to review its diagnosis and management, we retrospectively studied five such cases in patients from our institution and nine detailed case reports from the literature. The clinical manifestations were an acute (58%) or subacute (42%) febrile illness, typically associated with tenderness in the right upper quadrant, leukocytosis, a very high erythrocyte sedimentation rate, but minor abnormalities of liver function tests. Bacteremia was present in 7 of 11 patients. Enterobacteriaceae grew in pure culture from the cyst fluid in 9 of 12 patients. Complex cysts were observed by ultrasonography (in four of eight patients), computed tomography (in six of nine), and magnetic resonance imaging (in two of two). 111In leukocyte scans were positive in all four patients in whom they were done, and 67Ga scans were positive in only one of three patients. An unfavorable outcome was observed in six of seven patients treated with only antibiotics, in contrast with one of seven patients who received antibiotics and early drainage. In two patients, ciprofloxacin cyst levels were 2.3 and 4.8 times higher than the level in serum; in a third patient, cyst levels remained in therapeutic range 30 hours after the last dose of ciprofloxacin, at which time serum levels were undetectable. Clinical and laboratory features and the use of modern scanning techniques facilitate a prompt diagnosis of infection in hepatic cysts in ADPKD. The treatment of choice is a combination of percutaneous drainage and antimicrobial therapy. PMID- 2198397 TI - Infections related to central venous catheters. AB - Infection is a potentially life-threatening complication of central venous catheterization. Although line-related bacteremias and sepsis are relatively uncommon, the frequent use of central lines in the intensive-care unit makes these infections a common consideration. Semiquantitative culture techniques for analysis of the catheter tip provide evidence for the diagnosis of catheter related infections. Bacterial growth of more than 15 colony-forming units/plate is typically considered significant. Preventive measures include using sterile insertion techniques, providing meticulous care for the local site, and minimizing the duration of catheter use. The practice of changing lines over a guidewire is controversial. For treatment of most catheter-related infections, the catheter should be removed and antibiotics should be administered if associated systemic infection occurs. PMID- 2198398 TI - Medical symbols: Shou. PMID- 2198399 TI - Narcolepsy update. AB - Narcolepsy, a disorder of excessive daytime sleepiness that affects more than 125,000 people in the United States, is technically defined as a daytime mean sleep latency (time elapsed before falling asleep) of less than 5 minutes in conjunction with verification of rapid eye movement sleep in at least two of five daytime nap periods. Cataplexy, hypnagogic hallucinations, and sleep paralysis are frequently associated with narcolepsy. Currently, overnight polysomnography and multiple sleep latency testing in a sleep disorders laboratory are used to diagnose narcolepsy. Standard pharmacologic therapy consists of the judicious use of stimulants to improve alertness and the administration of tricyclic and other antidepressant drugs to suppress cataplexy. In addition, good sleep hygiene (a regular sleep-wake schedule, an adequate amount of sleep at night, and scheduled daytime naps) is essential for optimal management of this disorder. Patient and family education about narcolepsy and its treatment is also important. Even with use of the best available treatment regimens, many patients with narcolepsy have substantial vocational and social impairments. PMID- 2198400 TI - Restless legs syndrome and periodic movements of sleep. AB - Two entities of special interest in sleep disorders medicine are restless legs syndrome and periodic movements of sleep. Most patients with restless legs syndrome have periodic movements of sleep, but most patients with the nocturnal disorder do not have restless legs when awake. In both conditions, the underlying cause is obscure, and the frequency of occurrence increases with advancing age. In most patients with restless legs syndrome, the results of complete blood cell counts and iron, ferritin, folate, and vitamin B12 levels are normal. No hematologic or chemical abnormalities have been reported in patients with periodic movements of sleep who do not also have restless legs syndrome. Various pharmacologic agents, including benzodiazepines, opiates, and levodopa, have been proposed for the treatment of both disorders. Although some patients respond to a single drug for long periods, in many patients tolerance develops and the efficacy diminishes. In such circumstances, a reasonable approach is to alternate chemically unrelated agents on a weekly or biweekly schedule. Transcutaneous electric nerve stimulation may be beneficial. PMID- 2198401 TI - Computer imaging: dentistry's crystal ball. PMID- 2198402 TI - Analysis of the pressure perturbation due to the introduction of a measuring probe under an elastic garment. AB - Attention is drawn to the increase of the pressure on the skin due to the introduction of a measuring probe under an elastic garment. The increase of pressure is explained by looking at the force equilibrium on the transducer. Making some assumptions on the geometry and the conditions that actually prevail at the interface, this mechanical phenomenon is expressed mathematically. Expressions for estimating the order of magnitude of the relative pressure perturbation are derived both for the case of a cylindrical probe and for a thin plate probe with the same curvature as the limb. Thanks to the geometrical assumptions, these expressions are independent of the mechanical properties of the probe and the soft tissue. As in some of these formulas the magnitude of the indentation appears, a measurement is necessary for estimating the error. Other expressions, only taking in account the dimensions of the limb and the probe, give a rougher estimation of the error. It is shown through a few practical examples that the error cannot be disregarded and cannot be calculated precisely, which means that this measuring technique is unreliable. The same mathematical expressions are used to show that pressure paddings effectively increase the pressure. It is also shown that the introduction of an optical fibre under the garment, used in laser Doppler flowmetry, creates an important additional pressure on the skin. PMID- 2198403 TI - Architecture and design of a computerised stereogram generator for vision test. AB - A new microcomputer-based stereogram generator was designed and implemented to generate various visual stimuli that are used for testing the binocular vision system. The system is capable of generating static and dynamic stereoscopic stereograms that can be varied in size, shape, speed and disparity. It can also be used to generate a luminous stimulus on a dark background which, except for the depth parameters, can be varied in a similar way to the stereoscopic stimulus. A 16/32-bit microprocessor has been employed for the overall control of the stereogram parameters, which provides flexibility, versatility, compactness and speed at reduced cost. We have applied this system to the measurement of eye movement and computer vision. PMID- 2198404 TI - Simple system for automatic intermittent recording of blood flow in femoro-distal bypass grafts using Doppler ultrasound. PMID- 2198405 TI - Modified electrode surface in amperometric biosensors. AB - The electron transfer reactions of biological molecules are frequently very slow at ordinary electrodes. To overcome this problem, and thus to facilitate the direct coupling of biological redox reactions to electrodes for biosensor or bioelectronic applications, various types of modified electrode have been used. These include electrodes modified by the covalent attachment of species to the surface, by the reversible adsorption of promotors, or by the deposition of polymeric species, and the use of conducting polymers or conducting organic salts as electrode materials. Some of these different approaches are reviewed and their applications to biosensors and bioelectrochemistry are discussed. PMID- 2198406 TI - Optimisation of enzyme electrodes. AB - Enzyme electrodes have been fabricated in a variety of ways and used successfully for aqueous solution measurement. Knowledge about the fundamental basis of their operation has increased substantially in recent years, but the final, partly technological, hurdle of adaptation for practical use remains to be fully surmounted. Key aspects requiring attention are dependence on solution parameters capable of changing the kinetics of the immobilised enzyme reaction, direct fouling at the enzyme electrode, and the distorting effect of the biological matrix, notably blood and tissue, on the electrode environment due to the deposition of surface-active macromolecules and cellular elements. This review of enzyme electrode optimisation deals primarily with the various membranes which have been used to try to overcome such highly practical limitations to the biomedical use of enzyme electrodes. The classical amperometric glucose electrode based on detection of H2O2/O2 by the underlying sensor will be emphasised, but pH based sensors for pyruvate and urea will also be discussed. The amperometric systems described indicate that with appropriate covering membranes, many, though by no means all, interfacing problems can be overcome, and also that the type of optimisation engineered is dictated by the specific application envisaged. PMID- 2198407 TI - Sampling: a critical problem in biosensing. AB - Biosensing is widely recognised to be of potentially major importance to medicine and related fields, but in spite of a large number of impressive and important advances, widespread practical application has lagged. We examine the thesis that 'sampling' is a process which involves all of the phenomena which are associated with the transport of analyte molecules to the active sensor site, and that problems associated with this process are now the limiting factor in further use of many existing biosensors. We conclude that an integrated process of sampling and sensing should be emphasised in developing new biosensing systems, and propose several new approaches. PMID- 2198409 TI - [Serologic diagnosis of tuberculosis and other mycobacteriosis (II). Current situation of the serologic studies on these diseases]. PMID- 2198408 TI - In vivo chemical sensors for intensive-care monitoring. AB - There is a need for rapid assessment of a patient's biochemical status during intensive care so that therapies may be optimised. Chemical sensors for key species have the potential to allow continuous in vivo monitoring, and some progress is being made with certain sensors. Gases, ions and certain catabolites such as glucose and urea may be measured with devices based on mass spectrometric, electrochemical or optical principles. The physical form, and size of sensors must be matched to the measurement site, which can include the airway, the intravascular space, tissue and the skin surface. Electrochemical sensors for measurement of O2, pH and glucose have been the most widely used to date, although fibre-optic devices are currently attracting considerable interest. Invasive sensors still suffer from the problem of poor biocompatibility, particularly devices used in arteries and veins. Noninvasive methods may be successful in certain circumstances and in some patient groups, but peripheral measurements are often significantly influenced by circulatory phenomena such as shock. Further research is required if these limitations of both invasive and noninvasive sensors are to be overcome and continuous chemical monitoring is to be established as a routine clinical technique. PMID- 2198410 TI - [The prognostic value of liver function tests--clinical aspects, laboratory chemical parameters and quantitative function tests]. AB - In view of increasing therapeutic possibilities interest focuses on prognosis of liver cirrhosis. Until nowadays studies on prognosis revealed significant importance only for some parameters: Ascites, encephalopathy and portal hypertension as signs of decompensation, bilirubin, albumin and prothrombin time as laboratory indices of decreasing liver function. The commonly used Child-Pugh score is based on these parameters and allows a reasonable classification of diseased patients. Cholestasis and inflammation seem to be of minor prognostic importance. Assessment of liver function by quantitative tests is desirable (e.g. aminopyrine breath test, bile acids). The prognostic value, however, has not yet been proven in large studies. Use of these tests should therefore be restricted to studies (prognosis, therapy, indication to liver transplantation). PMID- 2198411 TI - [Stomach lymphomas in an endoscopy patient sample]. PMID- 2198412 TI - The pathology of the eye in armadillos experimentally infected with Mycobacterium leprae. AB - One hundred and twenty-seven eyes from 66 Mycobacterium leprae inoculated armadillos were studied histologically and some ultrastructurally. Inflammatory reactions were found in the following extraocular tissues: the eyelid, including the orbicularis muscle and the third eyelid, extraocular muscles, tear gland and Harder's gland. The early and slight changes of the intraocular tissues, small amounts of lymphocytes, plasma cells and macrophage infiltrations were confined to the area around the anterior angle specifically within the trabeculae and the adjacent ciliary body, the root of the iris and the limbus region of the cornea. But in the cases with severe lesions the whole uvea was densely infiltrated with large, foamy macrophages intermingled with small amounts of lymphocytes, plasma cells and frequently, neutrophils. No specific necrosis of the granulomas was seen. No explanation for the neutrophil infiltrations was given. The lesions in the cornea were significantly less severe than those in the uvea. Retinal lesions comprised of macrophage infiltrations were all obvious extensions of the adjacent uvea lesions. Acid-fast bacilla (AFB) were found within all tissues. The infection of the intraocular tissues in the armadillo eyes seemed to be mainly, if not solely, haematogenous. PMID- 2198413 TI - Experiences with Mycobacterium leprae soluble antigens in a leprosy endemic population. AB - Rees and Convit antigens prepared from armadillo-derived Mycobacterium leprae were used for skin testing in two leprosy endemic villages to understand their use in the epidemiology of leprosy. In all, 2602 individuals comprising 202 patients with leprosy detected in a prevalence survey, 476 household contacts and 1924 persons residing in non-case households were tested with two antigens. There was a strong and positive correlation (r = 0.85) between reactions to the Rees and Convit antigens. The distribution of reactions was bimodal and considering reactions of 12 mm or more as 'positive', the positivity rate steeply increased with the increase in age. However, the distributions of reactions to these antigens in patients with leprosy, their household contacts and persons living in non-case households were very similar. These results indicate that Rees and Convit antigens are not useful in the identification of M. leprae infection or in the confirmation of leprosy diagnosis in a leprosy endemic population with a high prevalence of nonspecific sensitivity. PMID- 2198414 TI - Evaluation of five treatment regimens, using either dapsone monotherapy or several doses of rifampicin in the treatment of paucibacillary leprosy. AB - The objective of the present study was to define short-course treatment regimens for PB leprosy and to compare them with the 'classical' dapsone treatment and the WHO-PB regimen. Five treatment regimens were studied and evaluated by the histologic evolution. The regimens were: (1) dapsone 100 mg daily, non-supervised for 3 years; (2) RMP 900 mg supervised, once weekly, 8 doses; (3) idem 12 doses; (4) RMP 600 mg, once monthly, supervised, 6 doses and during this treatment dapsone 100 mg daily unsupervised; (5) RMP 600 mg together with dapsone 100 mg daily, supervised for 6 days. For each of these regimens there were between 114 and 195 person-years of follow-up. Results are comparable for the 5 treatment regimens, and reach 65-75% cure rates at 36 months and 80-90% at 48 months after the start of therapy. The relapse rate for all groups is about 0.5% per year. The difficulty for the diagnosis of relapse in PB leprosy is discussed. It is concluded that treatment of PB leprosy can be relatively simple but that a relatively long time is needed to evaluate its effect. PMID- 2198415 TI - A study of relapse in paucibacillary leprosy in a multidrug therapy project, Baroda District, India. AB - In order to judge the value of therapeutic regimens in paucibacillary leprosy, knowledge of incubation time of relapses is essential, as this will define the length of time patients have to be followed up after treatment has been stopped. The prospective study of relapse includes paucibacillary cases of leprosy belonging to a non-lepromatous group consisting of tuberculoid, neuritic and indeterminate. Data are presented on the incubation time of 21 relapses after multidrug therapy in Baroda district; 76.19% of relapses occur during the first 2 years. This figure is most important in the analysis of results of drug trials in paucibacillary leprosy. This figure should also be relevant to regimens including drugs that are more bacteriocidal than dapsone, since the bacteriocidal activity has a bearing on the minimal necessary duration of treatment, but not on the incubation time of relapses. With the introduction of bactericidal drugs e.g. rifampicin in multidrug therapy, the incidence of relapse are very low, hence relapse rates fall down to a very low level after multidrug therapy. Our study shows a mean relapse rate of 0.19% after multidrug therapy. Factors associated with the occurrence of relapse are discussed. PMID- 2198416 TI - Leprosy control in Zimbabwe: from a vertical to a horizontal programme. AB - In Zimbabwe leprosy control services were re-established in 1983, following the war of independence. Its main objectives were the nation-wide implementation of multiple drug treatment (MDT) and the integration of leprosy control into the general health services. The MDT regimens have led to a rapid reduction of the prevalence of leprosy. At the beginning of 1989 357 patients were on treatment and 1299 under follow-up. Six hundred and twenty-seven new cases have been detected since 1984, which represents an annual case detection rate of 1.6 per 100,000. This seems a fair reflection of the incidence rate, as the new cases are characterized by a minority of patients under the age of 15 (4%) and a lepromatous percentage of 50%. As the budget of the programme has remained unchanged integration of leprosy control into the general health services has become imperative. However, this transition is now hindered by a number of obstacles that were not foreseen at the start of the programme, because they are in measure corollaries of the successful implementation of MDT. Most of the problems that leprosy control is facing in Zimbabwe could have been avoided if instruction in leprosy had been introduced into the curricula of the (para) medical training schools 20 years ago. PMID- 2198417 TI - Severity of leprosy eye lesions in armadillos infected with Mycobacterium leprae. PMID- 2198418 TI - Redefining health education in leprosy: a personal view. PMID- 2198419 TI - Corynebacteria: incidence among samples submitted to a clinical laboratory for culture. AB - Over the period of one year, 83 corynebacteria isolates were identified in our laboratory, and their clinical relevance assessed by reference to patients whose clinical notes were available. Eleven species of corynebacteria were identified including four biotypes of C. jeikeium; six organisms were non-typeable; C. jeikeium and C. xerosis predominated. Species identified in the literature as causing clinical infection were also isolated--though in smaller proportions--as were strains of C. jeikeium which were not multi-resistant to antibiotics. Immuno compromised patients and those with renal impairment had an increased frequency of corynebacteria. The isolation of C. jeikeium from the blood of a neonate suggests that this may be a potential pathogen in these patients. Antibiotic susceptibility of an organism was not a reliable marker of significance, and a reliable biotyping scheme should be adopted. PMID- 2198420 TI - Enteric pathogen screening: a multipoint technique with a simple numerical profile. AB - The use of peptone water sugars to screen non-lactose fermenting enteric isolates is expensive and has limited potential for identification. The multipoint system uses seven media from a commercial system containing either single sugars or biochemical substrates. Up to 20 organisms can be tested on each set of plates, the results being used to generate a four figure profile from which a presumptive identity can be obtained. This identity must still be confirmed, but the number of organisms requiring further investigation can be as low as one third of those following use of peptone water sugars. The multipoint system represents a rapid, more accurate and considerably cheaper alternative. PMID- 2198422 TI - [Ultrasonic diagnosis in gynecologic practice]. PMID- 2198421 TI - [Linda Smith's visit to Moscow]. PMID- 2198423 TI - [With what was Napoleon ill?]. PMID- 2198424 TI - [Lenin's humanism and public health (on the 120th anniversary of his birth)]. PMID- 2198425 TI - ["Live by truth and for others" (Petr Frantsevich Lesgraft)]. PMID- 2198426 TI - [The respiratory therapy service in the USA]. PMID- 2198427 TI - [A device based on the use of single-crystal microcomputers for auricular diagnosis and therapy]. AB - The paper treats of the problems related to the design of the apparatus and programmed means of a set up for auricular diagnosis and therapy based on the experimental and reported data the authors substantiate the selection of the modes of the set up running in the course of search for active acupuncture areas, their diagnosis and therapy, describe technical decisions aimed at the enhancement of the ergonometric and technical characteristics of the set up. Provide a block diagram of the set up and algorithm maintaining its work in different modes. PMID- 2198428 TI - [A complex unit EKGS3T-01 for ECG recording and processing with preserving the syndromal findings]. AB - Functional and technical parameters of the microprocessor diagnostic complex are being considered herein. It allows one to combine the automatic ECG data analysis and the possibility of the active participation in the processing of the cardiological information. PMID- 2198429 TI - [Microprocessor control devices in the apparatus for psycho- physiological studies]. PMID- 2198430 TI - Insulin resistance in rats with non-insulin-dependent diabetes induced by neonatal (5 days) streptozotocin: evidence for reversal following phlorizin treatment. AB - We have examined the effect of chronic (4 weeks) phlorizin treatment (osmotic minipumps) on tissue sensitivity to insulin in adult female rats with non-insulin dependent diabetes (NIDD) induced by streptozotocin (STZ) (80 mg/kg) administered 5 days after birth. Insulin sensitivity was assessed with the euglycemic hyperinsulinemic clamp technique in anesthetized animals. In the untreated diabetic rats, the basal glucose production (GP) and glucose utilization (GU) were increased (P less than .001), and both the liver and peripheral tissues showed insulin resistance. In the phlorizin-treated diabetic rats, postabsorptive plasma glucose levels were decreased and remained stable during the last 3 weeks of the treatment (142 +/- 3 mg/dL as compared with 308 +/- 19 in the untreated diabetic rats and 119 +/- 3 in the phlorizin-control rats); their percent glycosylated hemoglobin values returned to normal (3.2 +/- 0.2 as compared with 5.8 +/- 0.4 in the untreated diabetic rats); their basal plasma insulin levels (55 +/- 5 microU/mL as compared with 52 +/- 3 in the untreated diabetic rats and 130 +/- 10 in the phlorizin-control rats), their in vivo glucose-induced insulin secretion, and their pancreatic insulin content were kept unchanged. In the phlorizin-treated diabetic rats, the basal GP and GU were normalized. Following a submaximal or maximal hyperinsulinemia, GP was normally suppressed and GU normally enhanced. Phlorizin treatment in the control rats did not affect any of the above parameters. These data demonstrate that correction of hyperglycemia with phlorizin normalizes insulin action on glucose metabolism by the liver and peripheral tissues in this diabetic model. This is in line with the proposal that hyperglycemia per se can lead to the development of insulin resistance. PMID- 2198431 TI - In vivo enzyme activity in inborn errors of metabolism. AB - Low-dose continuous infusions of [2H5]phenylalanine, [1-13C]propionate, and [1 13C]leucine were used to quantitate phenylalanine hydroxylation in phenylketonuria (PKU, four subjects), propionate oxidation in methylmalonic acidaemia (MMA, four subjects), and propionic acidaemia (PA, four subjects) and leucine oxidation in maple syrup urine disease (MSUD, four subjects). In vivo enzyme activity in PKU, MMA, and PA subjects was similar to or in excess of that in adult controls (range of phenylalanine hydroxylation in PKU, 3.7 to 6.5 mumol/kg/h, control 3.2 to 7.9, n = 7; propionate oxidation in MMA, 15.2 to 64.8 mumol/kg/h, and in PA, 11.1 to 36.0, control 5.1 to 19.0, n = 5). By contrast, in vivo leucine oxidation was undetectable in three of the four MSUD subjects (less than 0.5 mumol/kg/h) and negligible in the remaining subject (2 mumol/kg/h, control 10.4 to 15.7, n = 6). These results suggest that significant substrate removal can be achieved in some inborn metabolic errors either through stimulation of residual enzyme activity in defective enzyme systems or by activation of alternate metabolic pathways. Both possibilities almost certainly depend on gross elevation of substrate concentrations. By contrast, only minimal in vivo oxidation of leucine appears possible in MSUD. PMID- 2198432 TI - The growth hormone clamp technique: inhibition of growth hormone release by growth hormone occurs independently of free fatty acids. AB - It has been suggested that growth hormone (GH) can inhibit its own release: in fact it has repeatedly been shown that an acute methionyl-GH (met-GH) infusion blocks the GH response to GH-releasing hormone (GHRH). However, met-GH infusions are accompanied by a significant increase of free fatty acids (FFA), which can block GH release. The aim of this study was to evaluate whether the inhibition of GH response to GHRH also occurs when lipolysis is pharmacologically blocked. Therefore, six normal subjects received GHRH, 50 micrograms intravenously (IV), after a 4-hour saline infusion and a 4-hour met-GH infusion (80 ng/kg/min, yielding a constant GH level of 33.6 +/- 4.63 micrograms/L), and GH release was evaluated during the following 2 hours. To prevent lipolysis, all subjects received on both occasions acipimox, an antilipolytic agent, 500 mg during the 6 hours before IV GHRH. GHRH induced a clear GH release during saline infusion (46.6 +/- 2.70 micrograms/L) and a scanty GH release during met-GH infusion (9.3 +/- 1.52 micrograms/L; P less than .01). Plasma levels of FFA, somatostatin, insulin-like growth factor I (IGF-I), and glucagon and serum insulin levels were unaffected, while blood glucose levels slightly decreased during saline infusion, but not during GH infusion. These data confirm that met-GH inhibits GHRH-induced GH release, and demonstrate that this inhibition is not mediated by FFA levels. PMID- 2198433 TI - Characterization of the late posthypoglycemic insulin resistance in insulin dependent diabetes mellitus. AB - The insulin effect (6.5 to 7.5 hours) following hypoglycemia was studied with the euglycemic clamp technique in eight patients with insulin-dependent diabeteses mellitus (IDDM). The results were compared with a control study with the same insulin infusion, but where hypoglycemia was prevented by a glucose infusion. Glucose production (Ra) and utilization (Rd) were evaluated with D-(3-3H) glucose infusion. Hypoglycemia (glucose nadir, 1.5 +/- 0.1 mmol/L) caused a marked increase in cortisol and growth hormone, whereas the release of adrenaline and, in particular, glucagon was low. The plasma free insulin levels were similar in the studies, including during the clamp periods. The glucose infusion rates (GIR) were significantly lower after the hypoglycemia as compared with the control study (control, 2.4 +/- 0.3; hypoglycemia, 1.5 +/- 0.3 mg/kg x min; P less than .05). Thus, hypoglycemia induces prolonged insulin resistance. The posthypoglycemic insulin resistance during a moderate hyperinsulinemic (approximately 30 mU/L) clamp was mainly due to a decreased insulin effect on glucose utilization (control, 2.9 +/- 0.2; hypoglycemia, 2.2 +/- 0.2 mg/kg x min; P less than .02), whereas the insulin effect on glucose production was not significantly different after hypoglycemia. PMID- 2198434 TI - Lack of effect of high-dose biosynthetic human C-peptide on pancreatic hormone release in normal subjects. AB - We studied the effect of high doses of biosynthetic human C-peptide on pancreatic hormone secretion in response to oral (75 g) and intravenous [( IV] 0.33 g/kg of D50%) glucose on normal volunteers. The infusion of human C-peptide at a rate of 360 ng/kg/min body weight, increased the plasma C-peptide concentration from a basal level of 0.32 +/- 0.04 pmol/mL to 38.5 +/- 1.8 pmol/ml. Overall, C-peptide had no significant effect on the serum levels of glucose, insulin, proinsulin, glucagon, and pancreatic polypeptide, either under basal conditions or following IV and oral glucose administration. However, small decreases in glucose and insulin concentrations that were not statistically significant were seen during the first hour after C-peptide infusion. The results of the present studies are therefore consistent with the conclusion that even supraphysiologic plasma concentrations of infused C-peptide do not affect basal insulin secretion or overall insulin secretory responses to oral or IV glucose. However, we cannot definitively exclude a small reduction in insulin secretion in the first hour after oral glucose ingestion. PMID- 2198435 TI - Diminished insulin sensitivity and increased insulin response in nonobese, nondiabetic Mexican Americans. AB - The contributions of diminished insulin sensitivity and decreased insulin response to the development of non-insulin-dependent diabetes mellitus (NIDDM) remain controversial. Nondiabetics in high-risk populations for NIDDM, including Pima Indians and Mexican Americans, are characterized by obesity and hyperinsulinemia relative to nondiabetics in the lower-risk white population. However, it is not clear to what extent diminished insulin sensitivity in the high-risk groups reflects obesity per se or is an inherent characteristic of these groups. Insulin sensitivity and secretion were determined in 10 nonobese, normoglycemic Mexican Americans (mean body mass index [BMI], 23.8 kg/m2) and 11 normoglycemic non-Hispanic whites (mean BMI, 22.5 kg/m2) using the intravenous glucose tolerance test (IVGTT) and the minimal model approach of Bergman et al. Age, BMI, sum of skinfolds, and the ratio of waist-to-hip circumference (WHR) were similar in both ethnic groups. Mexican Americans had decreased insulin sensitivity compared with non-Hispanic whites (4.06 +/- 0.72 in Mexican Americans v 7.56 +/- 1.13 in non-Hispanic whites, P = .017). The areas under the C-peptide and insulin curves were significantly greater in Mexican Americans than in non Hispanic whites (P less than .01), suggesting greater insulin secretion in the former. This study provides evidence for diminished insulin sensitivity and increased insulin response in young, nonobese, normoglycemic Mexican Americans. PMID- 2198436 TI - Effects of partial replacement of dietary fat by olestra on dietary cholesterol absorption in man. AB - Olestra, a nonabsorbable fat substitute comprising long-chain fatty acid esters of sucrose, had been previously shown to reduce cholesterol absorption in humans when ingested at a level of 50 g/d. To determine whether or not a lower level of dietary olestra would also reduce cholesterol absorption, we studied the effect of 7 g of olestra twice a day in 20 normocholesterolemic male inpatients in a double-blind, crossover trial. Two 6-day diet treatment and stool collection periods were separated by a 14-day washout period. Half of the subjects received butter, and half, a butter-olestra blend during each treatment period according to a crossover design. All subjects ingested trace amounts of 3H-cholesterol and 14C-beta-sitosterol with the butter or the butter-olestra blend. Cholesterol absorption was determined from the 3H/14C ratios in the diet and in saponified and extracted stools according to previously validated methodology. Cholesterol absorption during the butter regimen was significantly greater than that during the olestra regimen (56.1% +/- 1.6% v 46.7% +/- 1.1%, P less than .01). PMID- 2198437 TI - Regulation of plasma lactate concentration in resting human subjects. AB - We evaluated the relative contributions of glucose, insulin, and the rate of glucose disposal to the regulation of the plasma lactate concentration. Rates of glucose disposal were measured in 88 separate studies in whole body and across the forearm at varying plasma insulin (9, 50, 160, and 1,800 microU/mL) concentrations, and at each insulin concentration at four different glucose concentrations (90, 160, 250, and 400 mg/dL) in healthy male subjects. The rate of glucose disposal was positively correlated with the plasma lactate concentration (r = .83, n = 88, P less than .0001). When the plasma lactate concentration was adjusted for the rate of glucose disposal, plasma glucose or insulin concentrations did not contribute significantly to the residual variation in plasma lactate. When plasma lactate concentrations were compared at matched rates of glucose disposal, the lactate levels were similar regardless of whether glucose disposal was induced by hyperglycemia or hyperinsulinemia. At the lowest glucose and insulin concentrations, forearm tissues released lactate, but at all other glucose and insulin concentrations, no significant net lactate flux was observed. After subtraction of the rate of forearm glucose disposal from whole body glucose disposal, the plasma lactate concentration correlated with the remaining, extramuscular, rate of glucose disposal (r = .60, P less than .0001). These data suggest that in resting normal subjects the plasma lactate concentration may be determined by the rate of glucose disposal in extramuscular tissues, rather than the ambient glucose or insulin concentration. PMID- 2198438 TI - [The isolation and characteristics of Yersinia pestis membranes]. AB - A method for fractionation of membrane structures of Yersinia pestis is developed. It involves the following basic stages: the cultivation of bacteria in a liquid nutrient medium, mechanical destruction from the solid state in the X press or ultrasound treatment of the suspension, subsequent two-stage centrifugation in the step (70-15%) and linear (70-45%) gradients of the sucrose density, collection of fractions and their storage. The method makes it possible to separate rapidly and efficiently the outer and cytoplasmic membranes which preserve biochemical and morphological integrity. This is confirmed by the distribution pattern of marker enzyme activities, by the electron microscopic control as well as by other modern sediment tests. High heterogeneity of the polypeptide composition of the isolated membrane preparations has been shown by electrophoresis in PAAG in the presence of sodium dodecyl sulphate as well as definite sensitivity of certain protein subunits to variations of the temperature (28 or 37 degrees C) during cultivation of a plague agent. PMID- 2198439 TI - [The biological characteristics of micromycetes isolated from fish roe]. AB - The fungi Aspergillus fumigatus Fres., and Fusarium sporotrichiella Bilai were studied for their effect on certain biochemical indices of two-year carp and spawn of grass carp under laboratory conditions. The intraperitoneal introduction of A. fumigatus in a dose of 5 and 20 min conidia per individual to two-year carp decreased significantly the protein level in blood serum, the decrease being more considerable with the introduction of the smaller dose of fungal conidia. Joint incubation of the grass carp spawn and F. sporotrichiella induced changes in the protein level, amylolytic and phosphate (acid phosphatase) activity in spawn. In that case the time of the fungus action on grass carp spawn was a decisive factor. Activity of certain hydrolytic enzymes in mycelium and conidia of A. fumigatus and F. sporotrichiella was determined. The amylolytic activity was not revealed in the checked samples. The proteolytic activity was established in all samples of fungi and culture liquid, the highest level being observed in mycelia and conidia of A. fumigatus. The alkaline and acid phosphatase activity was found in F. sporotrichiella: the acid phosphatase activity was higher in mycelium, the acid phosphatase one in the fungus conidia. The problem on the A. fumigatus ability to produce extracellular enzymes is under discussion. PMID- 2198440 TI - [A toxicological evaluation of micromycetes isolated from salmon roe]. AB - Three species of micromycetes (Aspergillus clavatus Desm., Cladosporium herbarum (Pers) Lk., Penicillium canescens Sopp.) isolated from the cultivated salmon spawn have been studied for their toxigenic properties and pathogenicity for warm blooded animals. LD50 are determined for mice perorally administered mycelium suspension of the first two species; the third of the studied species proved to be nontoxicogenic. The possible pathogenic action of mycotoxins on fish spawn in aquarium is discussed. PMID- 2198441 TI - The age incidence of multiple sclerosis: a decision theory model. AB - It is proposed that multiple sclerosis (MS) arises as an auto-immune response to antigens shared by common commensal bacteria and brain tissues. In particular it is suggested that the causative bacteria are normally spread by the faecal-oral route but first exposure can occur in the nasopharynx, particularly following a viral respiratory infection, and this increases the risk of MS. The interaction between bacterial colonisation and the immune response is analysed in terms of an information model derived from statistical decision theory. The model predicts a finite chance of autoimmune disease on first exposure which rises with age at exposure. The predicted age incidence of MS, which is the resultant of the rising error function and the age incidence of first exposure to common bacteria, rises to a peak in the third decade and matches published age incidence data. Furthermore the model predicts that subsets of the population, such as women, in whom the risk of MS is increased will have an earlier mean age of onset. This accords with observation which is hitherto unexplained. The model also explains the decreased incidence of MS in equatorial regions, data on migration studies, and is consistent with the observation that the mean age of onset is not consistently lower in low incidence regions. It also offers an explanation for conflicting data on the effect of social class, economic conditions and birth order. The hypothesis is amenable to laboratory investigation and should be pursued. PMID- 2198442 TI - Autoantibodies in aging: an attempt to correct a weakening debridement mechanism. AB - Autoantibodies are present in small quantities throughout most of the host life but increase with aging. It is unlikely they are the etiologic cause of aging. They probably do contribute to some of the pathologic changes seen in aging such as amyloid deposits. Autoantibodies, when they are part of a functioning microdebridement system, like other antibodies, are one method of increasing tissue debridement. Autoantibodies are a broad biologic phenomenon capable of doing far more good than harm. Inflammation weakens with aging and thus microdebridement is weakened. The immune system weakens with aging but is stimulated by the increasing accumulation of antigen derived from tissue debris. Autoantibodies are an attempt to enhance debridement in a weakening system. The autoantibody should not be condemned because of the failure of other aspects of the debridement system. Improving tissue debridement would not stop eventual senescence but it might decrease some of the pathologic and physiologic changes of aging and improve the quality of life. Improving tissue debridement is currently more attainable than altering the etiology of senescence. Factors promoting immunologic stimulation by tissue fractions are reviewed. The possible value of increasing tissue debridement in damage preceding arteriosclerotic vascular change is discussed. The role of the aging extracellular matrix in the weakening of ground substance and decreasing early cellular inflammation is reviewed. PMID- 2198443 TI - The diagnosis of breast cancer: a clinical and mammographic comparison. AB - The early and accurate diagnosis of breast cancer is of paramount importance in the symptomatic patient. In this study, the sensitivity and false negative rates of clinical assessment and community mammographic imaging are measured and compared. One hundred and sixty-nine histologically proven breast cancers, derived from one surgeon's practice, were clinically assessed. Of these, 108 were additionally assessed by mammography. Eighty-seven per cent of the patients with breast cancer presented with a lump. In 82.8% of cases the patient or her partner found the lump, while 12.3% of lumps were found by the family practitioner. The false negative rate for clinical diagnosis was 19%, and for mammographic diagnosis it was 29%. Premenopausal mammographic diagnosis had a significantly higher false negative rate (54%) than postmenopausal diagnosis (14%). Mammographic examination had a particularly high false negative rate (65%) when cancer was thought clinically to be of "low index of suspicion". The clinical evaluation of and the indications for biopsy of the symptomatic breast remain the essential step in the diagnosis of breast cancer. PMID- 2198444 TI - An Australia-wide epidemic of Pseudomonas pickettii bacteraemia due to contaminated "sterile" water for injection. AB - Nineteen cases of Pseudomonas pickettii bacteraemia and one case of Pseudomonas cepacia bacteraemia were identified in an Australia-wide outbreak of nosocomial sepsis associated with contaminated water for injection. The contamination was limited to one batch of commercially produced water for injection. Four different organisms were identified (three biotypes of P. pickettii and one of P. cepacia). However, P. pickettii biotype 1 appeared to be relatively more virulent than the other biotypes as it was the only identified organism in blood cultures in nearly all cases of sepsis. The ampoules of "sterile" water were each contaminated with approximately 10(3) organisms per millilitre. The lack of an Australian central reporting system for bacteraemia delayed the recognition of this outbreak. PMID- 2198445 TI - The diagnosis and management of pathological anxiety. AB - The anxiety disorders are common reasons for patients approaching their doctors for help. While benzodiazepines used to be the treatments most commonly used, increasing concern about the wisdom of prescribing these drugs means that other treatments have to be considered. A differential diagnostic schema for patients who complain of anxiety is presented and an outline for counselling these patients is described. Treatment of the four major anxiety disorders is evaluated, and the efficacy of drug treatment compared to various levels of behaviour therapy. Cognitive behaviour therapy is recommended for all four disorders on the grounds of a short-term effectiveness comparable to drug therapy and evidence for stability of improvement after treatment has concluded, evidence that is lacking for the drug therapies. PMID- 2198447 TI - [Insulin therapy. Possibilities and limits]. PMID- 2198446 TI - Deafness: diagnosis and management. PMID- 2198448 TI - [Interleukin-1 production in patients with unilocular echinococcosis]. AB - The production of interleukin-1 (IL-1) by peripheral blood monocytes was estimated by the H. R. Recalde method (1984) in 45 patients with echinococcosis and 10 virtually healthy controls. In echinococcosis patients interleukin-1 turned to be significantly lower (p less than 0.05) than in the controls (Kact 1.2 +/- 0.1 and 2.2 +/- 0.1 respectively). In patients with a malignant course of the disease (mostly in those with disseminated lung damages) Kact of Il-1 was 0.93 +/- 0.1. In patients who underwent surgical interventions 1.5-6 years before Kact of Il-1 reached 1.43 +/- 0.1 but was still lower (p less than 0.05) than in the controls. The lowest production of IL-1 was identified in patients with lung disseminated lesions and bone damages (Kact 0.9 +/- 0.1 and 0.79 +/- 0.1, respectively). PMID- 2198449 TI - [Helminthic zoonoses in the Far North of the USSR]. PMID- 2198450 TI - [Opisthorchiasis, the pancreas and diabetes mellitus]. AB - The authors reviewed the data on pathogenesis, pathomorphology and clinical appearance of the incretory pancreatic involvement in opisthorchiasis patients. Besides, the authors presented their own data on the impact of opisthorchiasis invasion on the formation of diabetes mellitus. The concept of a diphasic involvement of the insular system was considered. PMID- 2198451 TI - [A modification of an immunoenzyme test system for the serodiagnosis of opisthorchiasis]. AB - Based on the antigen derived from the whole Opisthorchis marita extraction in cats and A-peroxidase protein conjugate the authors modified the enzyme immunoassay system for the detection of IgG antibodies to the causative agent of opisthorchiasis. A vibroshaker used in all stages of study permitted them to reduce the time of the reaction and its analysis providing the visualized consideration of the results. PMID- 2198452 TI - [Bronchoalveolar lavage: interim evaluation following 10 years clinical use]. PMID- 2198453 TI - [Therapy of obstructive respiratory tract diseases. III: Glucocorticosteroids]. PMID- 2198454 TI - [Acute adult respiratory distress syndrome. II: Therapy]. PMID- 2198455 TI - [Scoliosis and lateral gaze paralysis. Description of a case and review of the literature]. AB - The paper reports the case of a girl affected by progressive scoliosis and paralysis of the horizontal gaze, and reviews previously published cases. This is a rare and little known neurological entity transmitted by recessive autosomal inheritance. To all effects, this appears to be the first report of an Italian case. A correct early diagnosis is of considerable importance in view of appropriate genetic counselling. PMID- 2198456 TI - [Ultrasonic diagnosis of cerebellar hemorrhage in newborn infants. Apropos of 2 cases]. AB - The sonographic diagnosis of cerebral hemorrhage, in preterm infants is quite easy. On the contrary the prematurity degree of the patient and the anatomic location of the intracerebellar hemorrhage makes of this important lesion a difficult diagnosis to achieve. We present our results of 248 preterm infants scanned by ultrasound, in our Institute, to detect intraventricular or subependymal hemorrhage. Out of the 248 patients the incidence of SEH or IVH was 21%, only 1 case of intracerebellar hemorrhage, as complication of IVH-SHE, was found. Another intracerebellar hemorrhage was diagnosed in a full term newborn without other signs of hemorrhage. PMID- 2198457 TI - [Comparative study between carcinoembryonic antigen (CEA) in breast cancer tissue and morphological regional immunoreaction: preliminary report]. PMID- 2198458 TI - [Haemophilus influenzae type B. Disease and prevention]. AB - Haemophilus influenzae is a gram-negative rod, causing severe infections in childhood, including meningitis, sepsis, epiglottits, pneumonia and otitis. Most of the invasive infections are due to serotype b. Since ampicillin-resistance is increasing, modern cephalosporines like cefotaxime and ceftriaxone are the antibiotics of choice in severe disease. Bacterial meningitis due to Haemophilus influenzae and epiglottitis are both still life-threatening diseases with a lethality of 5% to 25%, and there are severe sequelae in 35% of meningitis cases. Efforts have been made to develop efficacious vaccines. While immunogenicity of type b polysaccharide was low in the high-risk age (below 18 months), conjugated vaccines with either diphtheria-toxoid or Neisseria meningitis outer membrane protein and the Hib polysaccharide were found to be strongly immunogenic even in the first months of life. These vaccines show every few side-effects and can easily be combined with other immunizations such as DPT and DT. Thus, the incidence of invasive infections due to Haemophilus influenzae type b might decline in future. PMID- 2198459 TI - [Pertussis: diagnosis, clinical aspects and therapy]. AB - Isolation of the causative agent remains the "gold standard" for the early diagnosis of pertussis. For this purpose, the nasopharynx is swabbed with a calcium alginate swab. Cephalexin-containing charcoal horse blood medium is used for the transport of the swabs to the bacteriology laboratory. As an alternative, the isolation of bordetellae can be performed at the paediatrician's office by direct inoculation of charcoal horse blood agar plates. Long-lasting cough of unknown aetiology is the main field for pertussis serology (ELISA). Even today, severe courses of whooping cough requiring hospitalization are not rare, especially in infants. Erythromycin (given in high doses for 14 days) is the antibiotic of choice for pertussis. As an alternative to the macrolides, cotrimoxazole may be administered or amoxycillin. Salbutamol and the corticosteroids have been shown to be useful for the symptomatic treatment of severe pertussis in infants. PMID- 2198460 TI - [Symptomatic HIV infection. Approaches to rational therapy]. AB - The symptomatic HIV-infection is characterized by the involvement of multiple organs with a predominance of infectious complications. Treatment of these complications usually follows established therapeutic regimens for the resulting diseases of affected organs. Successful reconstitution of the immunodeficiency resulting from HIV-infection has been unsuccessful so far. Recently, promising results have been obtained by the treatment of patients with antiviral substances which inhibit viral replication. The prototype substance, Zidovudine (AZT) has been proven to be beneficial for patients in advanced stages of the disease and more recently has been shown to delay the occurrence of full-blown AIDS in patients with AIDS-related complex. In consequence, substances with less side effects such as Dideoxycytidine or Dideoxyinosine are currently under investigation. PMID- 2198461 TI - [Color-coded Doppler sonography of renal vessels in childhood. I. Method and normal values]. AB - Doppler sonography allows measurement of renal blood flow velocities non invasively. Combination of pulsed Doppler with gray scale imaging (Duplex-scan) yields precise measurement of the flow in defined vessels. By means of the Duplex technique not only the flow parameters in the renal artery and vein can be measured, but also in the segmental, interlobar and interlobular arteries and veins. Colour coded Doppler sonography allows simultaneous display of the flow within the vessels and the gray scale image. With the help of colour coded Doppler sonography the sample volume of the pulsed Doppler device can be placed precisely within the vessels, which makes possible the determination of absolute flow velocities. Besides the flow velocities other different indices have been defined in the literature. All indices result from comparison of systolic and diastolic flow amplitudes in different ways. The flow parameters in the renal vessels are dependent on the site of the flow measurement and the age of the children. When pathologic flow parameters are analyzed the vessel and the age of the child have to be mentioned always. The interpretation of pathologic flow profiles becomes easier by knowledge of normal values for the flow velocities and the different indices. PMID- 2198462 TI - [The diagnostic value of captopril radionuclide nephrography for renovascular hypertension in childhood]. AB - In four children the role of captopril-radionuclide nephrography in the diagnosis of renovascular hypertension was studied. Captopril (0.5-1.0 mg/kg orally) did not affect Iodine-123 Hippuran nephrography in two children with mild renal artery stenosis, but induced an accumulation of the tracer within the kidneys in two children with hemodynamically significant renal artery stenosis. As in adults Iodine 123 Hippuran nephrography appears to be a useful tool to identify patients with significant renal artery stenosis. PMID- 2198463 TI - [Diagnosis and treatment of adnexa tumors in childhood and adolescence]. AB - From 1968 to 1988, 47 children and adolescents, their ages ranged from a few days to 21 years, were treated for tumors of the ovary in the hospital for children and adolescents and the surgical department of the University of Erlangen Nurnberg. In 33 cases ovarian cysts were found, 14 patients suffered from a neoplasm of the ovary. 8 of the neoplasms were benign cystic and solid teratomata, 4 were of epithelial origin and 2 identified as juvenile granulosa cell tumors. There was a follow up in all patients with tumors ranging up to 19 years. PMID- 2198464 TI - [Variability of clinical symptoms in neuronal intestinal dysplasia]. AB - Neuronal intestinal dysplasia is defined as a structural disorder of the innervation of the gut which clinically resembles Hirschsprung's disease. Between 1977 and 1988 12 patients were diagnosed by enzyme histochemistry. In 3 of these patients Hirschsprung's disease was associated. Constipation was the main symptom in 6 patients with neuronal intestinal disease and in all three patients with associated Hirschsprung's disease. The other patients firstly presented with an enterocolitis, a congenital atresia of the jejunum and a chronic enteritis with malabsorption. The wide clinical variability and the lack of a clear therapeutic management valid for all patients is conspicuous. PMID- 2198465 TI - Evaluation of the mutagenicity of 'pan masala', a chewing substitute widely used in India. AB - Mutagenicity of polar and non-polar extracts of a popular brand of 'pan masala' was examined using the Salmonella/mammalian microsome test (Ames assay) and 2 tester strains of Salmonella typhimurium, TA98 and TA100. These extracts were also subjected to pretreatment with sodium nitrite at acidic pH, to simulate conditions for endogenous nitrosation. The aqueous, aqueous:ethanolic and chloroform extracts as well as their nitrosated mixtures were non-mutagenic in the Ames assay, in the presence and absence of metabolic activation. Only the ethanolic extract elicited a weak mutagenic response in strain TA98 without metabolic activation demonstrating the presence of direct-acting frameshift mutagens in 'pan masala'. PMID- 2198466 TI - Mutagenic and recombinogenic consequences of DNA-repair inhibition during treatment with 1,3-bis(2-chloroethyl)-1-nitrosourea in Saccharomyces cerevisiae. AB - The yeast Saccharomyces cerevisiae has been used as a model system to explore whether the clinical combination of the antitumour agent BCNU (1,3-bis(2 chloroethyl)-1-nitrosourea) with DNA-repair inhibitors would affect the drug's mutagenic or recombinogenic potential. Preliminary experiments suggested that mitotic crossing-over and other mutagenic events are controlled in a separate fashion. BCNU was more toxic in yeast derivatives with specific defects in any of the three recognised major DNA repair pathways than in the DNA-repair-proficient parent strain. However, in a diploid homozygous for rad18, BCNU showed enhanced mutagenic and recombinogenic potential. Both of these effects were reduced in a comparable rad3 strain, and mitotic crossing-over but not other types of mutagenic event eliminated in the rad52 derivative. Experiments were performed in the presence of three DNA-repair inhibitors which are currently in clinical use and which might be available for combination chemotherapy. Hydroxyurea and amsacrine themselves caused mitotic crossing-over and other events, and did not reduce mutagenic or recombinogenic potential of the BCNU. Hydroxyurea actually decreased toxicity of the BCNU. Caffeine, however, showed some effect in enhancing toxicity and decreasing both mutagenic and recombinogenic potential of the drug. Development of more specific repair inhibitors related to amsacrine or to caffeine, using these repair-deficient strains as model systems, might lead to an enhanced clinical potential of this bisalkylating drug and related compounds. PMID- 2198467 TI - Geriatrics: sleep disorders and aging. PMID- 2198469 TI - The past and future of the association. PMID- 2198468 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 34-1990. A 74-year-old man with a failed right-hip replacement, constant pain centered in the right hip, and an osteolytic lesion in the right acetabulum. PMID- 2198470 TI - Primate evolution. African dawn for primates. PMID- 2198471 TI - Empty MHC class I molecules come out in the cold. AB - Major histocompatibility complex (MHC) class I molecules present antigen by transporting peptides from intracellularly degraded proteins to the cell surface for scrutiny by cytotoxic T cells. Recent work suggests that peptide binding may be required for efficient assembly and intracellular transport of MHC class I molecules, but it is not clear whether class I molecules can ever assemble in the absence of peptide. We report here that culture of the murine lymphoma mutant cell line RMA-S at reduced temperature (19-33 degrees C) promotes assembly, and results in a high level of cell surface expression of H-2/beta 2-microglobulin complexes that do not present endogenous antigens, and are labile at 37 degrees C. They can be stabilized at 37 degrees C by exposure to specific peptides known to interact with H-2Kb or Db. Our findings suggest that, in the absence of peptides, class I molecules can assemble but are unstable at body temperature. The induction of such molecules at reduced temperature opens new ways to analyse the nature of MHC class I peptide interactions at the cell surface. PMID- 2198472 TI - Stepwise phosphorylation of myo-inositol leading to myo-inositol hexakisphosphate in Dictyostelium. AB - Although myo-inositol hexakisphosphate (InsP6; phytate) is the most abundant inositol phosphate in nature and probably has a wide variety of functions, neither the route of its synthesis from myo-inositol nor its metabolic relationships with other inositol-containing compounds (such as the second messenger inositol 1,4,5-trisphosphate, Ins(1,4,5)P3) are known. Here we report that the pathway by which InsP6 is synthesized in the cellular slime mould Dictyostelium, and in cell-free preparations derived from them, is catalysed by a series of soluble ATP-dependent kinases independently of the metabolism of both phosphatidylinositol and Ins(1,4,5)P3. The intermediates between myo-inositol and InsP6 are Ins3P, Ins(3,6)P2, Ins(3,4,6)P3, Ins(1,3,4,6)P4 and Ins(1,3,4,5,6)P5. The 3- and 5-phosphates of InsP6 take part in futile cycles in which Ins(1,2,4,5,6)P5 and Ins(1,2,3,4,6)P5 are rapidly formed by dephosphorylation of InsP6, only to be rephosphorylated to yield their precursor. PMID- 2198473 TI - [The distribution of neurons in the caudate nucleus of the cat that respond to sensory stimulation and the organization of the topical projections]. AB - It has been shown in chronic experiments that cells responding to somatic and visual stimuli are unevenly distributed in the caudate nucleus of a cat and areas of high and low activity alternate. Representational maps of somatic and visual space in the caudate nucleus are not single. These data as well as those on the morphological heterogeneity of the caudate nucleus suggest the presence of multiple somato- and retinotopic maps projecting independently on striosome surfaces. PMID- 2198474 TI - [An electron microscopic study of the origins of the projections of the first auditory area of the cortex (AI) to the medial geniculate body in cats]. AB - An electron microscope study of retrogradely labelled neurons in layer VI of the primary auditory cortex (AI) after injection of the horseradish peroxidase to the medial geniculate body was carried out in cats. Three-eight synapses (4.6 +/- 0.6 at an average) were revealed on the somata profiles of these retrogradely labelled cortico-geniculate neurons. Synapses occupied 10.8 +/- 1.0% of the somatic profile of cortico-geniculate neurons. Almost all (98.7%) of these axosomatic synapses had symmetrical contacts and were formed by axonal terminals with small elongated synaptic vesicles. HRP retrogradely labelled axonal terminals of geniculo-cortical fibres were revealed in neuropil of layer VI. They contained large round synaptic vesicles and formed asymmetrical synapses, mainly on spines. The role of axo-somatic synapses in regulation of the activity of cortico-geniculate neurons was discussed. PMID- 2198475 TI - [Dystrophia myotonica (Steinert disease)--a frequently misdiagnosed disease]. AB - Dystrophia myotonica (Steinert's disease) is the most common hereditary disease of the neuromuscular system in adults. Its mode of inheritance is autosomal dominant. The gene responsible for its is located on chromosome 19 in the linkage domain of the loci for the apolipoproteins C2, C1 und E and of the creatine kinase of skeletal muscle (CKMM). Myotonic dystrophy is categorized in an adult and in a congenital form. In the adult form, the characteristic findings are muscular atrophy in certain regions of the body (face, neck and distally in the extremities) and myotonia. Cataract, intraocular hypotension, gonadal atrophy, conduction abnormalities in the heart and hearing deficiencies appear quite often in the course of the disease. In the congenital form, general muscle weekness (particularly pronounced in the face) is the leading finding, combined with retarded loco motor and mental development. A decisive criterion for the diagnosis of this form is the occurrence of myotonic dystrophy in the patient's mother. Electromyographic investigation is indicated when a suspicion of myotonic dystrophy cannot be ascertained on the basis of clinical and genetic findings. Myotonic runs in the EMG will then corroborate the suspicion. Recent electrophysiological investigations have indicated that at least three different types of channels for the passage of ions through the membrane of the skeletal muscle cells show abnormal behaviour, i.e. the channel for Cl-, Na+ and K+. These findings corroborate the hypothesis that the abnormality responsible for myotonic dystrophy is situated in the membrane systems. A pharmacological treatment of the muscular dystrophy has not yet been developed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198476 TI - [Neurologic problems in HIV infection. A current overview]. PMID- 2198477 TI - [Immunoadsorption in the treatment of Guillain-Barre type polyradiculitis]. PMID- 2198478 TI - [Vertigo caused by neurovascular compression, "vestibular paroxysm"?]. PMID- 2198479 TI - [Comments on the contribution by D. F. Braus et al. Significance of stereotaxic brain biopsy in atypical multiple sclerosis]. PMID- 2198480 TI - The molecular basis of brain injury and brain edema: the role of oxygen free radicals. AB - This review article outlines basic concepts and pathophysiological aspects of the chemistry of oxygen free radicals in all forms of brain injury and brain edema. Recent experimental studies have demonstrated that oxygen free radicals may be important mediators of brain injury and brain edema, and pharmacological antagonism of oxygen free radicals shows beneficial therapeutic results. A number of fundamental questions need to resolved, and advanced techniques for detecting oxygen free radicals will be needed. No clinical data are available, but oxygen free radical scavengers may possibly become a critical therapeutic modality for brain injury and brain edema. PMID- 2198481 TI - Evaluation of posttraumatic cerebral blood flow velocities by transcranial Doppler ultrasonography. AB - Thirty-five patients were admitted to the hospital with Glasgow coma scale scores of 4 to 7 after severe, blunt head injury. Blood flow velocities of the middle cerebral artery (MCA) and the ipsilateral internal carotid artery (ICA), high in the neck, were recorded noninvasively by Doppler ultrasonography. Serial examinations were begun within 48 hours of trauma and continued until the patient either died or was discharged. Spasm of the MCA was assumed if the ratio of the velocity of blood flow in the MCA (VMCA) to the velocity of blood flow in the ICA (VICA) exceeded 3 (normal value, 1.7 +/- 0.4). In cases of severe MCA spasm, this ratio is higher because of increased flow velocity in the MCA and reduced flow in the ICA due to increased cerebrovascular resistance. Higher MCA velocities with VMCA/VICA above 3, consistent with MCA spasm, were found in 14 of the 35 patients (40%). The increase began as early as 48 hours after injury, reached a maximum between Days 5 and 7, and lasted until 2 weeks after injury. There was a significant correlation between the occurrence of vasospasm and the quantity of cisternal or intracerebral blood seen on a computed tomographic scan. No correlation was found with the age of the patients, the Glasgow coma scale score at admission, the intracranial pressure, or the functional outcome 6 months after injury. The occurrence of a secondary infarction in a patient with severe MCA spasm suggests that, at least in some cases, spasm may influence the prognosis. PMID- 2198482 TI - Congenital fistula of the dural carotid-cavernous sinus: case report and review of the literature. AB - The case of a 2-month-old boy with a congenital fistula of the dural carotid cavernous sinus is presented. This is a rare vascular anomaly in infancy, and it may cause acute changes in vision. The child was initially followed up for 1 year to see if spontaneous thrombosis would occur. The symptoms persisted, however, and intravascular surgery using platinum coils was performed for closure. After treatment, the symptoms completely resolved. Literature pertaining to this anomaly has been reviewed with particular emphasis on dural fistulas of the cavernous, transverse, sigmoid, and straight sinuses in infancy. PMID- 2198483 TI - Symptomatic arachnoid cyst at the clivus drained stereotactically through the vertex. AB - A 40-year-old man had an acute ischemic event affecting the pons. He had no cardiac illness or vasculities and was not diabetic or hypertensive. The contrast enhanced computed tomographic scan disclosed nothing abnormal, and a vertebral angiogram showed an avascular mass markedly displacing the basilar artery and pons posteriorly and toward the right. A magnetic resonance image clearly delineated a homogeneous arachnoid cyst containing cerebrospinal fluid. To avoid manipulating posterior fossa arteries, after the recent pontine stroke, this arachnoid cyst with unusually favorable anatomical landmarks was approached stereotactically through the vertex. Fenestration and drainage of the cyst was accomplished under local anesthesia and benzodiazepine sedation with low morbidity. The procedure was well tolerated, and the patient returned to gainful employment shortly afterward. He remains asymptomatic at 3 years' follow-up. The successful outcome of this case suggests that in carefully selected symptomatic arachnoid cysts, stereotactic interventions could become a useful surgical alternative. Stereotaxis may also be helpful in other cumbersome surgical cases in which a second port for contrast injection or simple manipulation would be advantageous. PMID- 2198484 TI - Primary intracerebral plasma cell granuloma: a light, immunocytochemical, and ultrastructural study of one case. AB - A case of primary intracerebral plasma cell granuloma without meningeal attachment is presented. Histologically, the lesion showed two different patterns. At the center, it displayed the features of a benign fibrous histiocytoma. At the periphery, a mixture of polyclonal plasma cells, lymphocytes, and "epithelial-like" cells was observed. Electron microscopy and immunocytochemistry confirmed the histiocytic nature of the "epithelial-like cells." The differential diagnosis and histogenesis of such a lesion are discussed. PMID- 2198485 TI - Cavernous angioma of the cavernous sinus: case report. AB - An unusual case of cavernous angioma in the cavernous sinus ("cavernous cavernoma") is presented. The acute onset of symptoms simulated Tolosa-Hunt syndrome, and after neuroradiological investigations, the suspected diagnosis was an intracavernous meningioma. Macroscopical intraoperative and histopathological findings demonstrated a cavernous angioma. The lesion was completely removed from the cavernous sinus without additional neurological deficits and with improvement of the symptoms. Three additional cases in the literature are reviewed. The rarity of these lesions and the management problems related to their location in the cavernous sinus are stressed. PMID- 2198486 TI - Interventional neuroradiological management of vein of Galen malformations in the neonate. AB - Since 1978, the authors have seen 14 neonates with vein of Galen malformations who were born with severe congestive heart failure. The 5 infants treated before 1983 underwent craniotomy and clipping of feeding vessels; all died in the perioperative period. Since 1983, 8 neonates have been treated with combined arterial and venous interventional neuroradiological techniques; 6 infants survived. Two-dimensional echocardiography, color Doppler flow imaging, and pulsed Doppler ultrasound were used to assess blood flow within the malformation before and after staged transluminal embolic procedures were performed. The results of the diagnostic studies and the clinical status of the infants were used to evaluate the success of embolic therapy and the need for further neuroradiological intervention. PMID- 2198487 TI - [Current approach in the treatment of Zollinger-Ellison syndrome]. AB - On the basis of six surgically operated patients, current thinking with regard to the treatment of Zollinger-Ellison syndrome is outlined. Total gastrectomy which for many years was the most common surgical intervention, is now confined to just a very specially indicated few cases because the introduction of anti-H2 gives good control of gastric secretion. The operation should therefore be targeted at removing the gastrinoma, helped in this by modern methodologies for pinpointing the neoplasia. Long-term however include a certain number of failures. PMID- 2198488 TI - [Manual and mechanic anastomosis. Comparison in oncologic surgery of the colon and rectum]. AB - Personal experience in the treatment of 60 cases of cancer of the large bowel with left hemicolon and rectal localisation is reported. 20 manual double layer anastomoses (group I), 20 single layer (group II) and with mechanical stapler (EEA stapler) (group III) were carried out in consecutive series. The results are reported in terms of early local and general complications: specifically 13 cases of anastomotic dehiscence of which 69.2% were observed in group I, 15.4% in group II and 15.4% in group III. Total postoperative mortality was 5%, average hospitalisation was as follows: 19 days group I, 14 days group II, 17 days group III. The value of single layer anastomoses, which is comparable to results with the stapler whose use is essential in cases of real manual technical difficulty, is stressed. PMID- 2198490 TI - [Treatment of traumatic oto-hematoma with transfixed compression sutures]. AB - The effective early treatment of oto-hematoma is important so as to prevent reaccumulation of fluid and the typical chronic "cauliflower ear" deformity. A simple method of treatment with the use of transfixed tie-through compression mattress sutures, incorporating bolster dressings on both surfaces of the ear, following drainage of the hematoma via a small skin incision, is presented. This allows an optimal immobilisation of the skin over underlying cartilage for 7-10 days, preventing the reaccumulation of fluid with subsequent thickening and fibrosis, frequent complications of the other current methods of treatment. PMID- 2198489 TI - [Distal gastrectomy with Y gastroenteroanastomosis not associated with vagotomy in elective surgical treatment of gastroduodenal ulcer. Clinical and functional long-term results]. AB - During the period 1977-1984, 53 patients with peptic ulcer resistant to H2 blockers (29 gastric and 24 duodenal ulcers) were submitted to distal gastrectomy with Roux-en-Y gastroenteroanastomosis not associated with vagotomy. The indication was used as an alternative to proximal vagotomy in cases with delayed gastric emptying, high acid output, perforation or bleeding. The study plan consisted of serial clinical and instrumental controls including determination of basal (BAO) or maximal (MAO) acid output. Operative mortality was nil. At various times after the operation, 4 patients died for unrelated reasons and 3 were lost to follow-up. Median follow-up was 84 months with an interval of from 4 to 137 months. Fifty-one patients were followed up for at least one year and 49 for at least two. Five patients (2 gastric and 3 duodenal ulcers) developed peptic recurrences (Visick IV, 9.8%) by the end of the first postoperative year and, in all cases but one, healed stably by the second year after medical (3 cases) or surgical (1 case) therapy. In the remaining patients, Visick was grade III in 6 cases (4 gastric and 2 duodenal ulcers), grade II in 6 and grade I in 34. Before operation, mean values (+/- SD) of BAO and MAO were respectively 5.84 +/- 5.03 and 29.6 +/- 18.6 mEq/h. In the immediate postoperative period there was a considerable reduction in BAO (p less than 0.02) and MAO (p less than 0.03) which continued up to the third postoperative year with a tendency to further progressive reduction in MAO. In spite of a considerable individual variability in dimensions and temporal evolution, the phenomenon occurred qualitatively in all cases. No significant difference was observed in the behaviour of BAO and MAO in gastric ulcers by comparison with duodenal ulcers and in cases with recurrence and Visick III compared to those with a favourable clinical result. PMID- 2198491 TI - [Differential diagnosis of acute abdomen and latrodectism]. AB - Among the causes of pseudo-acute abdomen the Latrodectism, or poisoning by malmignatta spider Latrodectus mactans tredecimguttatus bite, is often forgotten in Italy, Unfortunately, it is common knowledge that its severe clinical picture sometimes induces the surgeon to make diagnostic mistakes, and to unnecessary laparotomy. The Authors briefly describe the toxic syndrome and supply the first principles for a correct differential diagnosis to acute abdomen. PMID- 2198492 TI - [Aneurysm of the left gastric artery. Clinical contribution and review of the literature]. AB - The extra-visceral aneurysms of the gastric arteries are very rare and their diagnosis occurs mostly in the presence of haemoperitoneum and shock due to their rupture. Through echography and selective arteriography a right diagnosis can be made before a rupture. The treatment is surgical with good results but treatment with embolisation through arteriography is preconized. Two cases treated in emergency are reported. PMID- 2198493 TI - [Carcinosarcoma of the lung]. AB - The Authors report about one surgical case of pulmonary carcinosarcoma recently observed. The literature is reviewed and the histogenesis of this rare affection is discussed. PMID- 2198494 TI - [Diabetic enteropathy]. AB - This review of the literature is designed to identify the state of our knowledge about the ileal, colonic and biliary damage arising in diabetes mellitus. The approach is primarily clinical with the emphasis on the major symptoms involved: diarrhea, constipation and anal sphincter incontinence. The most common symptom, found in 20% of diabetics with neurological disease, is constipation. While the peculiar features of diabetic diarrhea have been well described, there is considerable controversy over its pathogenesis. As for sphincter dysfunction, manometric examinations will already reveal the autonomic neuropathy involved in the early asymptomatic phase. There is considerable debate over the possible involvement of the gallbladder in diabetes mellitus. Some believe that the autonomic neuropathy is involved in the pathogenesis of the lithiasis and helps to mask the pain in cholecystitis as well. PMID- 2198495 TI - [Bone densitometry. A critical review and the authors' own experience]. AB - After an updated review of computerised bone densitometry, personal experience of the bone density found in healthy subjects and rheumatoid arthritis patients both those treated with prednisone and untreated is reported. In addition certain biohumoral parameters like bone calcium, PTH, CT and l'1-25 (OH)2D3 were investigated. The results show significantly lower levels of bone calcium in treated than untreated patients. PMID- 2198496 TI - [Paget's disease of bone: recent findings]. PMID- 2198497 TI - [Primary empty sella syndrome (ESS). Clinical observations on 20 cases]. AB - The authors report 20 cases of primary empty sella syndrome (ESS) observed during the last 5 years in their Department of Internal Medicine. Clinical data and particular syndromes are discussed and compared with data of partially reviewed literature. The authors discuss the classification of primary and secondary ESS with their possible endocrine, ophthalmological and neurological symptoms, or--on the contrary--without clinical signs as more frequently observed. The usual diagnostic and therapeutic procedures are also reported. PMID- 2198498 TI - [The function of trace elements in human nutrition and their possible role in neoplastic disease]. PMID- 2198499 TI - [Thymopentin as adjuvant therapy in the hepatitis B vaccination of non- or hyporesponsive subjects]. AB - The efficacy of thymopentin as adjuvant therapy was assessed in 13 people who did not respond to standard anti-hepatitis B vaccination with Pasteur HEVAC or Merck HV-VAX. Thymopentin (Sindtomodulina, Italfarmaco)--was given in doses of 50 mg 3 times a week for 3 consecutive weeks, a booster dose of the vaccine (40 mcg HB VAX injected into the deltoid muscle, or 10 mcg HEVAC subcutaneous) being given at the start of the second week. In 69.23% of the patients whose anamnesis revealed no immune deficiency, the Merrieux Multitest showed defective cell mediated immunity. The adjuvant treatment produced an adequate immune response to the vaccine (anti ABc antibody titre 10 mU/ml) in 76.9% of cases and normalised cell-mediated immunity in 66.6% of those found to be hypoanergic at basal screening. PMID- 2198500 TI - Generator mechanisms of epileptic potentials analyzed by dipole tracing method. AB - A new dipole tracing method, based on a realistic head model, was used to determine dipole locations and vector moments of interictal convexity sharp waves recorded (with conventional EEG technique) from the right fronto-temporal region in a patient with partial complex seizures. When the dipole locations in the head model were compared to MRI scans, the majority of the sharp wave dipoles were found to be located in the right hippocampal area. For individual sharp waves, the hippocampal dipoles moved along tracks corresponding to the vector moment directions, suggesting that the electrical sources of the convexity sharp waves were somato-dendritic currents which spread rapidly from one neuron group to the next in the hippocampal area. Previous long-term subdural recording had shown seizure onset in this area. After right-sided anterior temporal lobectomy including the hippocampus the patient has been seizure-free for three months. PMID- 2198501 TI - Wound management. Computer assisted learning. PMID- 2198502 TI - Adrenal morphologic considerations in polycystic ovary syndrome. PMID- 2198504 TI - Polymers of prolactin and their clinical significance. AB - Elevated levels of prolactin are known to cause a range of disturbances of ovarian function. However, in a small number of women, sustained hyperprolactinemia has been found by chance in association with apparently normal ovarian function and normal fertility. In these women the dominant form of circulating prolactin has been found by gel chromatography to be a polymeric form of large molecular size, 'big-big' prolactin (BBPRL), with similar immunoreactivity to monomeric prolactin (PRL) but much lower biological activity. In a few cases an intermediate polymeric form, 'big' prolactin (BPRL), has also been described. The exact nature and biological significance of polymeric forms of prolactin remain unclear. It has been shown that concentrations of BBPRL in the circulation in individual women change more slowly and less profoundly than concentrations of PRL in various physiological and pharmacological situations. Minor changes occur during the menstrual cycle, while increases of PRL and BBPRL occur progressively during pregnancy. In pregnancy PRL rises much more than BBPRL. Acute stimulation with metoclopramide, TRH, or suckling favors the production of PRL, although BBPRL also rises to a small extent. During treatment with bromocriptine the proportion of PRL in the circulation is markedly reduced, while BBPRL falls to a much lesser extent. Further study is required before it can be proved that BBPRL and BPRL have no biological significance. There is much controversy regarding the structure and mechanism of production of polymeric forms of prolactin. There is no evidence of a circulating factor in serum which binds several molecules to form BBPRL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198503 TI - Cancer in pregnancy: identification of unanswered questions on maternal and fetal risks. PMID- 2198505 TI - The frequency of platelet alloantibodies in pregnant women and the occurrence and management of neonatal alloimmune thrombocytopenic purpura. AB - Neonatal alloimmune thrombocytopenic purpura (NAITP) is induced by maternal antibodies to fetal platelet alloantigens. The disease is rare, but is often responsible for intracranial hemorrhages leaving severe neurological damage. Although this occurrence is rare, its frequency may be underestimated. In order to determine the frequency of alloimmunization to platelet antigens, serum from pregnant women were investigated in platelet-ELISA and lymphocytotoxic test (LCT). Seventy-eight out of 556 pregnant women (14%) were found to have antibodies to platelet antigens in ELISA and/or LCT. In one case (0.18%) a platelet specific antibody, anti-Zwa(-PIA1), was found in the platelet-ELISA. In all of the other cases only HLA-antibodies were detected. The only mother who was delivered of a child with clinical NAITP was the woman with anti-Zwa(PIA1) in serum. Furthermore, in a review from the currently available literature the following items will be discussed: 1) human platelet antigens involved in NAITP, 2) clinical aspects and prognosis of NAITP, 3) immunological diagnosis of NAITP, and 4) prevention and treatment of the disease. PMID- 2198506 TI - Learn to relax and counter stress. PMID- 2198507 TI - The Morning Glory syndrome associated with sphenoethmoidal encephalocele. AB - A 10-month-old infant was referred to the ophthalmic department of the Royal Victoria Hospital for assessment. Pregnancy and delivery had been normal. At birth, cleft lip, cleft palate, hypertelorism and a soft tissue mass in the mouth were noted. At two days of age he developed meningitis, axial computerized tomography showed a sphenoethmoidal encephalocele, and agenesis of the corpus callosum. The basal encephalocele was surgically repaired. On examination in the ophthalmic department he was able to follow a light with the left eye. He perceived light with the right eye but did not follow. There was a manifest right divergent squint, measuring -10 degrees, and a right afferent nerve defect. Examination under anaesthetic was performed. The right fundus showed a Morning Glory syndrome. The disc was pink and deeply excavated, and surrounded by a ring of chorioretinal pigmentary disturbance. There was a central tuft of glial tissue. The left fundus was normal. The association of Morning Glory syndrome and basal encephalocele is rare; four previous cases have been reported. In all patients there were associated mid-facial congenital anomalies such as cleft lip and cleft palate. The presence of a basal encephalocele should be suspected if the Morning Glory syndrome occurs in association with mid-facial congenital anomalies. PMID- 2198508 TI - [Current trends in perinatal mortality statistics at the New Jersey Obstetric Center]. AB - The study presents an overview of the changes in perinatal mortality rates at the Statewide Perinatal Center of New Jersey during the past decades. According to the data, the increase in the rate of cesarean sections from 4.5 percent to 17 percent, and the comparable reduction of the rates of manipulative intrapartum and extraction procedures, contributed significantly to the decrease of the perinatal mortality rates from 51/1000 to 17/1000 between 1971 and 1983. Of the new technical tools, those utilized for the evaluation of fetal well-being antepartum appeared to be more useful then those used intrapartum. On account of the high prevalence of genital infections in the population, the recent acceptance in the service of the use of invasive intrapartum technology, appears to have impacted unfavorably upon the perinatal mortality trends. The increased rate of births of premature babies, the widespread abuse of habit forming drugs in the community, and the routine use of procedures requiring artificial rupture of the membranes, probably all contributed to the rapid increase of the perinatal mortality rate in the Center from 15/1000 in 1986 to 28/1000 in 1988. It is concluded that perinatal care is a complex medical and social task. The overall result of the relevant efforts depends to a great extent upon the social environment, and the moral standing, educational level and motivation of the recipients. PMID- 2198509 TI - [Serum cortisol and ceruloplasmin determination in neonates with intrauterine growth retardation]. AB - The authors have shown recently that coeruloplasmin deficiency was associated with severe respiratory distress in premature neonates. In the present study they measured the serum cortisol and coeruloplasmin levels in 58 intrauterine growth retarded infants. The results were compared to the data of 44 appropriate for gestational age neonates. Both parameters showed association with the fetal distress in term babies (cortisol: 17.2 vs 12.3 ug/100 ml, coeruloplasmin: 29.7 vs 11.9 U/l). Coeruloplasmin activity was also higher in growth retarded prematures (48.5 vs 16.5 U/l), while cortisol concentration increased irrespective of intrauterine malnutrition. There was a significant positive correlation between serum cortisol and coeruloplasmin in dysmaturity. This is the first report suggesting a possible role for coeruloplasmin, an important extracellular antioxidant enzyme in the precocious development of intrauterine growth retarded infants. PMID- 2198510 TI - [T-lymphocyte subgroups and the activity of human natural killer cells in non Hodgkin lymphoma of moderate and high malignancy]. AB - T-lymphocyte subgroups and the percentage and the activity of Human Natural Killer cells (HNK) were investigated by the authors in their 24 patients suffering with low grade and 24 with high grade malignancies of non-Hodgkin lymphoma (NHL). According to their observations, the ratio of CD3, CD4, Leu-7, and HNK cells as well as the release by HNK cells of 51Cr bound to target cells decreased, depending on the pathological stage. The tests were performed with monoclonal antibodies. A significant change could also be observed in the reactivity of bone marrow cells to monoclonal sera, which showed complete correspondence in character with the behavior of lymphocytes isolated from peripheral blood. No significant changes could be observed in the quantitative relations of immunoglobulins. Discussing the supposed immunological relation in detail, the role of plasma factor that reduces the formation of T-lymphocytes, is assumed to have primary importance in this phenomenon. PMID- 2198511 TI - [The role of exchangeable sodium content of the body in cases of hypertension of various etiology]. AB - Measurement of exchangeable sodium by isotope dilution is a relatively simple, reliable method for the determination of body sodium contents, which can be used in the clinical practice without significant health hazard to the patient. When computed to body surface area, the values for exchangeable sodium can be compared in patients of different body build. Exchangeable sodium may be variably increased in different clinical conditions associated with hypertension, thus increased sodium contents of the body is of major importance in the pathogenesis of hypertension caused by all forms of mineralocorticoid excess, and in the majority of patients with chronic renal insufficiency. In several endocrine disorders, e. g., acromegaly, hypothyroidism, increased sodium space does not play any significant part in the pathogenesis of hypertension. In diabetes mellitus, exchangeable sodium may be increased already prior to the development of hypertension, however it is still a matter of debate whether this abnormality is involved in the pathogenesis of hypertension in these patients. It seems now beyond any doubt that body sodium is normal in patients with essential hypertension, including those with the low renin form of the disease; nevertheless, some data indicate that blood pressure may be volume dependent in elderly patients with essential hypertension. PMID- 2198512 TI - [The 125th anniversary of the birth of Gyula Magyary-Kossa (1865-1944), the great master of Hungarian medical historiography]. PMID- 2198513 TI - [Ultrasonic methods used in the diagnosis of changes in the carotid artery system]. AB - The duplex method has been recommended as the most effective means, because it is able to detect both morphological and hemodynamical changes, respectively. The duplex is also useful in screening and follow up of stroke patients and the number of conventional angiography can be reduced. Any other ultrasonic diagnostic methods (B-mode, directional Doppler etc.) have a more little diagnostic accuracy but they can be used as complementary methods rising the diagnostic effectiveness. The author summarizes also his own experiences with different ultrasonic equipment compared with angiography. The B-mode has a diagnostic accuracy of 78%. This method is most useful in detecting of stenoses of small and medium size. The diagnostic accuracy of directional Doppler ultrasonography of periorbital vessels has an accuracy of 95% in detecting stenoses greater than 50%, but this method provides no information about the morphology and localization of plaques. The measurement of common carotid artery flow by UQFM--1000 (ultrasonic quantitative flow measurement) was diagnostically effective only in patients with completed occlusion. PMID- 2198514 TI - [The role of SPECT-supported three-phase scintigraphy of red blood cells in the diagnosis of liver hemangioma]. AB - The roles of planar and SPECT 99mTc labeled red blood cell (RBC) scintigraphy in the diagnosis of hepatic cavernous hemangioma were evaluated. Out of the 29 patients with various focal intrahepatic lesions 13 were diagnosed as having hemangiomas: 6 proven by surgery, and 7 proven by maintaining stable clinical course ranging from 6 to 12 month with no change in the size or appearance of the lesion on US. In the 13 patients a total of 16 hemangiomas were found. 12 of these detected by planar imaging, 2 detected by SPECT only. The sensitivity of planar RBC scintigraphy was 75%, the specificity was 100%. Although planar imaging is probably sufficient for all large or superficial hemangioma, delayed SPECT should be used with small (2-3 cm) or deeply seated lesions. PMID- 2198515 TI - [Vitamin D-induced tissue calcinosis and arteriosclerosis changes. I: A contribution to the 60 year history of vitamin D research with special reference to childhood]. AB - Already in 1927, a short time after the detection of the vitamin D, the danger of a hypervitaminosis was put into the field of view. Overdoses of vitamin D may effect calciferous infiltrations in the soft tissue and arteriosclerotic changes. These findings are important especially under consideration of the up-to-now large-dosed vitamin-D-application in the field of the rachitis-prophylaxis. The appearance of nephrocalcinoses could have been demonstrated in predisposed infants and children suffering from disorders in calcium metabolism. In order to optimize the rachitis-prophylaxis in the GDR we comment on the problems and dangers by vitamin-D-overdosages on the basis of animal-experimental and clinical examinations. PMID- 2198516 TI - [Vitamin D-induced tissue calcinosis and arteriosclerosis changes. II. Current knowledge and conclusions for preventive vitamin D administration in infancy and early childhood]. AB - By means of the actual literature we clear up that vitamin-D is considered to be a risk factor for arteriosclerosis. In vitamin-D-susceptible children elevated vitamin doses may--to begin with--lead to a nephrocalcinosis and--subsequently- to a coronary sclerosis. The combination of a nourishment, rich in calcium, an over-supply of vitamin-D, and high cholesterol-contents, is considered to be especially unfavourable. In order to avoid a potential danger of arteriosclerosis the rachitis-prophylaxis in infants and babies should be taken up with physiological vitamin-D-dosages. PMID- 2198517 TI - NAON: the first decade. A firm foundation for a successful future. PMID- 2198518 TI - Crush syndrome: pathophysiology and management. AB - Crush syndrome is characterized by a predictable sequence of events that include hypovolemia, compartment syndrome, rhabdomyolysis and acute tubular necrosis (ATN). Cardiac dysrhythmias are common. Pathophysiology, current management, and a plan of nursing care for patients with crush syndrome are presented. PMID- 2198519 TI - The physiologic responses to the use of a pneumatic antishock garment (PASG) in the care of the patient experiencing shock. AB - The Pneumatic Antishock Garment (PASG) remains a controversial therapy. This article examines the benefits of the garment as well as the potential complications. PMID- 2198520 TI - Understanding therapeutic beds. AB - The use of "high-tech" therapeutic beds has increased during the past 5 years as a result of advances in medical technology, the early stabilization of trauma patients, and changes in the reimbursement system. Orthopaedic nurses need to understand how specialty beds can help them more effectively care for the immobilized patient. This article provides an overview of five categories of therapeutic beds along with criteria for patient selection, reviews of pertinent scientific studies, and relevant nursing considerations. PMID- 2198521 TI - [Effect of antibiotics on bacterial adherence to foreign material]. AB - Microbial adherence is the first step of foreign body infection. In vitro and ex vivo experiments have studied the mechanisms of the anti-adherent effect of antimicrobial agents. Adherence of bacteria onto foreign bodies is a complex phenomenon where several factors from the bacteria, the foreign body and the host, are involved. Bacterial factors are physicochemical factors such as cell surface charges, hydrophobicity, and adhesins such as exopolysaccharides or "slime". Foreign body factors are irregularities of the surface and hydrophobicity. Human factors are serum proteins as fibronectin, collagen, laminin and vitronectin, which are deposited onto the material and act as receptors for bacteria. In vitro models can study the interactions between the bacteria, the foreign body and the antimicrobial agent. They can be useful to analyse the molecular mechanisms of the effects of the antimicrobial agents on microbial adherence. Different studies have shown: 1) no relation between the effect of antimicrobial agents on microbial adherence and their bacteriostatic or bactericidal effects, 2) antimicrobial agents of the same class may have different effects on the same strain, 3) no correlation between effect of antimicrobial agents on microbial hydrophobicity, slime production or fibronectin receptors, and effect on adherence. PMID- 2198522 TI - [Antibiotics and anti-inflammatory agents: drug interactions]. AB - Antibiotics (AB) are sometimes used in patients taking anti-inflammatory drugs (AID) (steroidal and non steroidal anti-inflammatory drugs). At the present time, the usefulness of AID in bacterial infections has been established in a limited number of clinical situations. AID are able to modify the kinetics of AB through different mechanisms which are illustrated by results obtained with cephalosporins and phenylbutazone or diclofenac. In some conditions, these modifications might have consequences on in vivo effect of AB. Conversely, some AB are able to alter metabolism and/or kinetics of some steroids. Interactions of AI on AB toxicity have also been investigated on kidney and central nervous system. AB/AI kinetic interactions have to be investigated for a better understanding of the mechanisms through which AI improve the evolution of an infectious process. PMID- 2198524 TI - [Antibiotherapy in chronic familial granulomatosis]. AB - Antibacterial therapy in chronic granulomatous disease requires antimicrobials active on Staphylococcus aureus and enterobacteria, which also have a good intracellular penetration and activity as rifampicin, fluoroquinolone, fosfomycin, cotrimoxazole. Several trials showed that cotrimoxazole was effective for the prevention of bacterial infection: thus, this antimicrobial can be used as long-term and continuous prophylaxia. Fungal infections require the use of amphotericin B. The place of new imidazole compounds as itraconazole should be assessed. PMID- 2198523 TI - Mycobacteria, cytokines and antibiotics. AB - We still do not understand the mechanism of immunity ty mycobacteria in man, and convincing reproducible kill of M. tuberculosis by human macrophages has not been achieved. The pathways so far elucidated, involving gamma interferon, 1,25(OH)2 vitamin D3, and TNF release seem more likely to lead to immunopathology than to protection. Meanwhile the major problem for the clinician is the existence of "persister" bacteria, which are not eliminated by the immune response, even when therapy has greatly reduced the bacterial load. It seems unlikely that it will be possible to design antibiotics which will rapidly kill dormant persister bacilli, so new strategies for therapy may need to concentrate on modulation of the host response. The objectives of such therapies would be: 1) "Reawakening" of dormant persisters. 2) Rapid immune recognition of persisters. 3) Suppression of the tissue-damaging pathway. 4) Enhancement of the optimally protective mechanism, but this has not yet been defined. PMID- 2198525 TI - [Therapeutic aspects of salmonellosis in AIDS]. AB - For the HIV positive patient, salmonella raises numerous epidemiological and therapeutic problems. This microorganism, quite common before zidovudine therapy, seems to have diminished since this antiviral also has an antibiotic activity against salmonella. When bacterial contamination occurs, the decreased immunitary activity might play a role, but hypochloridria, frequently afflicting these patients, might also be involved. Therapeutically, antibiotics with high intramacrophagic diffusion yield excellent results and limit the incidence of recurrence. The effect of gamma interferon is well documented in vitro. However, the efficacy of these quinolones does not lead us to believe that it is the treatment of choice. PMID- 2198526 TI - [Antibiotherapy in the patient with granulocytopenic cancer]. AB - Granulocytopenia is the leading alteration of the natural host defense mechanisms, whether caused by an underlying disease or associated with anticancer chemotherapy and radiation therapy. Severe granulocytopenia predisposes to septicemia which is now more often due to Gram positive than to Gram negative bacteria. The empiric therapy of febrile episodes with rapidly bactericidal antibiotics has dramatically modified the prognosis of septicemia. The optimal treatment remains controversial although the usual regimen include both a cephalosporin (or a large spectrum penicillin) with an aminoglycoside. The empiric treatment with a specific anti-Gram positive antibiotic such as vancomycin does not modify prognosis, adds significant side-effects and increases the cost. Monotherapy has been associated with the need for treatment modification in 30-80% of the episodes depending on the type of infection (fever of unknown origin, clinically or microbiologically documented infection). The patients who remain febrile despite adequate antibacterial empiric treatment beneficiate of an empiric antifungal treatment. Care should be taken about the recent emergence of vancomycin-resistant Staph. haemolyticus, Corynebacterium JK and non-JK, and non-aeruginosa pseudomonas (only susceptible to cotrimoxazole). More fungal infections are observed with a significant emergence of non-albicans Candida, dermatophytes and filamentous fungi (P. boydii, Fusarium, ...) associated with disseminated infections. PMID- 2198527 TI - Elevated c-myc expression in childhood medulloblastomas. AB - Medulloblastoma is a rare brain tumor usually occurring in late childhood or early adolescence. Little is known regarding the cell of origin or cellular events leading to its malignant transformation. We have studied the expression of developmentally regulated mRNA in tumor samples by the Northern hybridization assay to determine a relative stage at which a block to further differentiation occurs. In a series of five medulloblastoma tumors analyzed, only one of eight markers for cellular differentiation, the glial fibrillary acidic protein mRNA, was expressed at significant levels. Interestingly, three of six medulloblastoma tumor samples were found to have elevated levels of c-myc mRNA. In one of these tumors, we have found evidence of mutation of the c-myc protooncogene. We discuss possible mechanisms of c-myc activation in medulloblastoma tumors. PMID- 2198528 TI - Effects of parental presence/absence on size of children's human figure drawings. AB - The effects of parental presence or absence in the home on the size of male and female human figure drawings were examined for a sample of 480 Barbadian children ages 7 to 13 yr. Most children of both sexes drew larger female than male figures, but significant effects relating to mother-absence and father-absence were found for boys and girls, respectively. Findings were not entirely consistent with those of previous research but would seem to reflect the matrifocality of Caribbean households. PMID- 2198529 TI - Effect of instructions given to reactors and nonreactors to produce visual imagery sequences following an imagined pleasant scene. AB - 15 Visual Imagery Reactors and 15 Nonreactors were instructed to produce Visual Imagery Sequences using as a point of departure a pleasant scene imagined by themselves. Despite these instructions, Reactors developed significantly less pleasant scene materials, more High and Low Affect/Conflict, less Neutral Content, and briefer sequences preceding all Affect/Conflict. Four Reactors and no Nonreactors expressed difficulty in visualizing pleasant scenes. Reactors made more interruptions when attempting to continue imagery of the pleasant scene. Several additional scores occurred almost exclusively within a subgroup of Reactors. These results are consistent with previous studies using different test stimuli and are congruent with previously advanced theoretical formulations. PMID- 2198530 TI - The gene map and genome organization. PMID- 2198531 TI - Treatment of acute myeloid leukemia in elderly patients: the influence of maintenance therapy (BGM 84 protocol). AB - Ninety-two elderly patients (ages 50-70) with "de novo" acute myeloid leukemia were given induction chemotherapy consisting of aclacinomycin-A (ACLA) (100 mg/m2/day x 3) and cytosine arabinoside (ARA-C) (100 mg/m2 day, continuous infusion, 7 days). Fifty-one patients (55%) achieved complete remission (CR), 8 patients exhibited drug resistance and 33 patients died during chemotherapy or aplasia. Three patients had severe cardiac toxicity. The only prognostic factor significantly affecting CR was the initial leukocyte count. After consolidation using ACLA (80 mg/m2/day x 2) and ARA-C (100 mg/m2/day x 5), 47 CR patients were randomly assigned to 2 different treatment arms: 23 patients (Group A) received intensive sequential chemotherapy consisting of 4 monthly courses of 8 different drugs while 24 other patients (Group B) were given ACLA and ARA-C at regular intervals, associated with continuous chemotherapy consisting of 6 mercaptopurine, methotrexate and androgens. The probability of disease-free survival at 2 years was significantly higher (33 +/- 22%) for Group B patients than for Group A (13 +/- 16%) (P less than 0.05). We conclude that continuous maintenance chemotherapy may be useful in increasing the number of long-term survivors, at least in the elderly who have not received very intense consolidation chemotherapy following CR. PMID- 2198532 TI - Alternative base pairing between 5'- and 3'-terminal sequences of small subunit RNA may provide the basis of a conformational switch of the small ribosomal subunit. AB - The compiled sequences of small subunit ribosomal RNAs have been screened for base complementary between 5'- and 3'-terminal regions. Highly conserved complementary sequences are found which allow formation of a helix between the two ends of 5 or 6 base pairs. This helix is composed of sequences from the loop region of the first 5'-terminal stem and from sequences immediately distal to the last stem (the Me2A-stem) of the 3' terminus and therefore allows a coaxial stacking with either of these two flanking stems. Formation of the 5'/3'-helical arrangement is, however, only possible at the cost of dissolving the 'pseudo knot' helix between the 5'-terminal region and the internal region of small subunit RNA. It is postulated that the mutually exclusive conformational states are in dynamic equilibrium and that they correlate with distinct functional states of the small ribosomal subunit. The 'pseudo-knot' containing conformation with the 3'-terminal sequences more exposed is likely to represent the initiating state, whereas the 5'/3' terminal paired 'closed' conformation may represent the elongating state in which interaction with fortuitous ribosomal binding sequences of mRNAs is avoided. PMID- 2198533 TI - Study of Vitreoscilla globin (vgb) gene expression and promoter activity in E. coli through transcriptional fusion. AB - Bacterial hemoglobin (VtHb) is produced by the gram-negative bacterium, Vitreoscilla, in large quantity in response to hypoxic environmental conditions. The vgb gene coding for VtHb has been cloned in E. coli where it is expressed strongly by its natural promoter. The expression of the vgb gene in Vitreoscilla is transcriptionally regulated by oxygen. When E. coli cells were shifted from 20% to 5% oxygen, vgb specific transcript increased. In E. coli cells with plasmids carrying transcriptional fusions of the vgb gene promoter to either CAT (chloramphenicol acetyl transferase) or xylE (catechol-2,3-dioxygenase) genes, the promoter activity depended on the oxygen level. The concentration of CAT and xylE gene products in cells grown under 5% oxygen was 5-7 times that of aerobically (20% oxygen) grown cells. When the vgb gene promoter was deleted, VtHb was not produced under any conditions. When the promoter was replaced by the E. coli tac promoter, hypoxic oxygen did not affect the level of expression of vgb, but adding IPTG did increase the expression of this gene. These results indicate that the vgb gene promoter is transcriptionally regulated by oxygen even in E. coli, and that microaerobiosis is sufficient to induce vgb expression. The size of S1 nuclease-resistant hybrids, prepared using RNA transcripts protected with restriction enzyme fragments containing the promoter proximal region of vgb, was the same for both Vitreoscilla and E. coli, further evidence that the same promoter is used in both organisms. Transcriptional fusion of the vgb gene promoter to the xylE reporter gene on the broad host range plasmid, pKD-49, was used to demonstrate that the vgb promoter can be expressed in other gram-negative organisms, including Pseudomonas, Azotobacter, and Rhizobium. PMID- 2198534 TI - Transcriptional regulatory elements of the RAS2 gene of Saccharomyces cerevisiae. AB - We have analyzed a series of 5' deletions of the RAS2 gene to investigate its complex transcriptional regulation in the yeast Saccharomyces cerevisiae. Two positive transcriptional regulatory elements were identified. Element A regulates two of the three clusters of RAS2 transcripts. This element is capable of activating a heterologous promoter and contains two copies of the sequence CCTCGCCCC. Although one copy is sufficient for partial transcriptional activation, both copies are required for maximal RAS2 induction. Deletion of one copy resulted in a reduced level of RAS2 mRNA, selective loss of cluster II transcripts and reduced ability to activate the heterologous CYC1 promoter. Each of the 9 bp C rich repeats of element A is part of a sequence with extensive homology to a transcriptional regulatory element upstream of the human epidermal growth factor receptor (EGFR) gene. Element B contains a tandem duplication of a 21 nucleotide sequence TACATATATATATATCTTAG and activates cluster I RAS2 transcripts in the absence of Element A. The physiological role of these deletions was determined by assaying their ability to support growth on a nonfermentable carbon source. RAS2 promoter deletions containing either element A or B were able to overcome this growth defect characteristic of ras2 mutants cells. Deletion of both elements resulted in an insufficient amount of RAS2 protein for growth on a non-fermentable carbon source. PMID- 2198535 TI - Expression of yeast 5S RNA is independent of the rDNA enhancer region. AB - In the yeast Saccharomyces cerevisiae, each of the tandemly repeated ribosomal RNA genes carries a 5S gene within the 'non-transcribed' spacer region. These 5S RNA genes lie between the rDNA enhancer and the promoter of rRNA transcription. Since there is roughly equimolar synthesis of 5S RNA and the 35S rRNA precursor transcript we asked whether the enhancer plays a role in regulating the transcription of 5S RNA. A marked 5S gene was inserted into plasmids designed to test rDNA enhancer function. The enhancer failed to stimulate 5S RNA synthesis even though it stimulated transcription of a distal rRNA test gene greater than 10-fold. This failure is consistent with a model of enhancer function that proposes specific interactions between the enhancer and the 35S rRNA promoter via a looping out of the intervening 5S RNA gene. PMID- 2198537 TI - Branch capture reactions: effect of recipient structure. AB - Branch capture reactions (BCR) contain two DNA species: (i) a recipient restriction fragment terminating in an overhang and (ii) a displacer-linker duplex terminating in a displacer tail complementary to the overhang as well as contiguous nucleotides within the recipient duplex. Branched complexes containing both species are captured by ligation of the linker to the recipient overhang. Specificity depends upon branch migration and is increased by substitution of bromodeoxycytidine for deoxycytidine in the displacer. BCR rates and specificities were determined for recipient overhangs that were (i) 5' and 3', (ii) 3 and 4 nucleotides long, and (iii) 0-100% G+C. Model systems permitted independent determination of G+C and branching effects on ligation rates and verification of rapid equilibrium between the branched complex and its component species. With all 4-base overhangs, recipient duplexes permitting extensive branch migration became saturated with displacer-linker duplexes. With increasing G+C, increasing ligation at competing sites led to decreased BCR specificity. BCR may be used to label a DNA fragment prior to electrophoresis, mark a fragment for affinity chromatography, or introduce a new overhang sequence compatible with a restriction endonuclease site in a cloning vector. A protocol was confirmed for mapping restriction sites in cloned DNA. PMID- 2198536 TI - In vitro capping in Trypanosoma cruzi identifies and shows specificity for the spliced leader RNA and U-RNAs. AB - Messenger RNA maturation in trypanosomes requires a trans-splicing event in which a capped 39 nucleotide leader sequence, the spliced leader (SL), from the 5' terminus of a small RNA (SL-RNA) is joined to the 5' termini of protein coding gene transcripts. We have developed nuclear extracts from Trypanosoma cruzi that label three small endogenous RNAs in the presence of [alpha-32P]GTP. Herein, we have characterized this labelling as 5' capping and shown that the capping activity exhibits an unusual ATP dependence. Moreover, partial sequence analysis identified the three cap-labelled RNAs as the T. cruzi SL-RNA, and two U-RNAs previously uncharacterized in T. cruzi, U2 and Ux. Finally, the capping reaction in the T. cruzi extracts showed apparent specificity for these RNAs--other endogenous or exogenous transcripts were not capped. The apparent specificity of this in vitro capping activity closely reflects the in vivo requirements; i.e., only the SL- and U-RNAs need to be capped since mature mRNAs are capped via trans splicing. These observations are consistent with the hypothesis that one of the functions of trans-splicing is to supply 5' caps to mature trypanosome mRNAs. PMID- 2198538 TI - Yeast tRNATrp genes with anticodons corresponding to UAA and UGA nonsense codons. AB - Naturally occurring suppressor mutants derived from tRNATrp genes have never been identified in S. cerevisiae. Oligonucleotide-directed mutagenesis was used to generate potential ochre and opal suppressors from a cloned tRNATrp gene. In vitro transcription analyses show the ochre suppressor form of the gene, TRPO, accumulates precursors and tRNA in amounts comparable to the parent. The opal suppressor, TRPOP, accumulates 4-5 fold less tRNA. Both forms of the gene are processed and spliced in vitro to produce tRNAs with the expected base sequences. The altered genes were subcloned into yeast vectors and introduced into yeast strains carrying a variety of amber, ochre, and opal mutations. When introduced on a CEN vector, neither ochre nor opal suppressor forms show suppressor activity. Deletion of the CEN region from the clones increases the copy number to 10-20/cell. The opal suppressor form shows moderate suppressor activity when the gene is introduced on this vector, however, the ochre suppressor form exhibits no detectable biological activity regardless of gene copy number. Northern blot analyses of the steady state levels of tRNATrp in cells containing the high copy number clones reveal 20-100% increases in the abundance of tRNATrp. PMID- 2198539 TI - A putative flagellar Ca2(+)-binding protein of the flagellum of trypanosomatid protozoan parasites. PMID- 2198540 TI - Nucleotide sequence of the Salmonella serC gene. PMID- 2198541 TI - Nucleotide sequence of endothelin cDNA from bovine endothelial cells. PMID- 2198542 TI - New vectors for expression of the E.coli lacZ gene in Dictyostelium. PMID- 2198543 TI - Three component system consisting of host bacteria, phage and plasmid, for efficient gene expression controlled by the SP6 promoter. PMID- 2198545 TI - Coming of age. PMID- 2198544 TI - Helping a dependent patient. PMID- 2198546 TI - [Children with hemorrhagic diathesis: correct diagnostic and therapeutic approach]. AB - Bleeding defects are of great interest in pediatrics since the prevalence of congenital forms and the early appearance of acquired ones. The pathology itself and the therapy indeed can often interfere with the growing-up patients. Bleeding defects have been identified with an heterogeneous group of clinical disease that differs from one another in etiology, pathogenesis, epidemiology and incidence in population. Bleeding diathesis is the common symptom: bleeding tendency may be mild, moderate or severe, localized or generalized, cutaneous or mucosal, superficial or deep. Bleeding disorders may be classified as a) defects in the primary haemostasis, which include quantitative and qualitative abnormalities of platelets and vascular disorders and b) defects in secondary haemostasis, which include intravascular disorders (blood coagulation). Careful history and clinical examination are essential in diagnosis of bleeding disorders. History of patient should be taken a) to differentiate acquired from congenital disease and to know the way of hereditary transmission (family history); b) to know exactly the disease's start and the mutual relation with former or accompanying disease; c) mutual relation with drugs token. Subsequently a careful physical examination should be done. A specific hemorrhagic diathesis has been seen with a deficiency of primary or secondary haemostasis. A deficient or late haemostatic plug in small vessels can cause superficial, interstitial bleeding that may be intracutaneous or intramucosal and is called purpura. In coagulation factor deficiency the haemostatic plug cannot be consolidated by fibrin: spontaneous hematomas, hemarthrosis and ecchymoses often occurs. The initial laboratory work up for screening patients with bleeding disorders should include first step tests to differentiate bleeding disorders for bone-marrow malignancies; from virus infections carrying screening of major viruses and from hepatic diseases. Second step laboratory examination includes a) platelet count or estimation of platelet number on blood smear; b) bleeding time to test small vessel integrity and platelet function; c) aPTT, PT, AP to measure clotting activity; d) fibrinogen determination. With this battery of screening test it is usually possible to determine the general area of the defect (abnormalities of platelets number or function or congenital defect of one or more clotting factors activity). Acute idiopathic thrombocytopenic purpura is the most common bleeding disorders in childhood. Usually no therapy may be required no matter platelet count. Patients with a significant hemorrhagic tendency are treated either with prednisone (2 mg/kg orally in divided daily doses) for a period of 2 weeks or with a 5 days course of special polyvalent intact immunoglobulin (400 mg/kg/die) for intravenous use.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2198547 TI - [Treatment of neonatal hyperbilirubinemia]. AB - Hyperbilirubinemia remains one of the most common and more important pathological conditions in the newborn. The possibility that low levels of serum bilirubin could be responsible for bilirubin encephalopathy in the small premature infant is of great concern for the neonatologist. In fact, premature newborns, as recognized more than 70 years ago by Y1ppo, are prone to develop hyperbilirubinemia. The so-called physiologic of developmental hyperbilirubinemia could be harmful for the small preterm infant, who is at risk of developing bilirubin encephalopathy in the presence of low plasma bilirubin concentrations. Current methodologies for suppressing severe neonatal jaundice include: 1) Attempts to stimulate liver conjugating enzymes by drugs, such as phenobarbital. 2) Attempts to degrade bilirubin "in vivo" by phototherapy. 3) Exchange transfusion. It is too soon to consider Sn-protoporphyrin as a drug for the prevention and treatment of neonatal hyperbilirubinemia. However, if it can be shown that the use of tin-protoporphyrin can serve as a safe and less costly alternate treatment, a considerable improvement in the management of neonatal jaundice will be achieved. PMID- 2198548 TI - [Neutrophil chemotaxis. II. Clinical implications and therapeutic indications in children]. AB - Defects of neutrophil chemotaxis are usually accompanied by recurrent or chronic infections of the skin and the respiratory tract. The onset of clinical symptoms may occur early in infancy; infections tend to be severe and they are generally due by organisms which are of relatively low pathogenicity in the healthy subject. Abnormalities of neutrophil chemotaxis were classified and described as humoral, cellular and unclassified defects. The relevance of neutrophil chemotaxis in the single clinical entities was discussed, taking in particular account the most recent views on the argument. Some details on practical and theoretical therapeutic approaches were also reviewed. PMID- 2198549 TI - [Brain tumors: classification and clinical aspects]. AB - Brain tumors represent 40% to 50% of all solid tumors in children under 18 years of age, with an average incidence of 2 to 5 cases per 100,000/annum. These tumors are gliomas in 60% to 70% of cases. The most common location is infratentorial (60% of cases), with cerebellar astrocytomas, medulloblastomas and brain stem gliomas occurring in equal measure (20%). Astrocytomas are the predominant form (25%) in the supratentorial compartment. This review analyses clinical symptoms and instrumental procedures for the diagnosis of various types of brain tumor, together with recommendations for their management based on controlled clinical trials. PMID- 2198550 TI - [Intracranial aneurysm in children. Peculiar clinico-radiologic aspects and the choice of surgical timing]. AB - The authors report their experience with 11 patients in pediatric age affected by intracranial aneurysms. They try to reply to the question: "Are aneurysms congenital?" and consider the different problems concerning clinical suspect of intracranial haemorrhage. Vasospasm is an important prognostic factor in adults but in children it doesn't affect surgical "timing" as it happens in older patients. Since the incidence of rebleeding in patients treated conservatively is very high, Authors conclude that a prompt surgery in necessary in these young patients. PMID- 2198551 TI - [Psycho-affective and relational aspects of children with congenital cardiopathy]. AB - The psychological and relational problems present in pediatric patients with congenital cardiac anomalies and in their families are reviewed based on an analysis of the current literature and on the personal experience of the authors. The need for all caretakers, especially the cardiologist and the cardiac surgeon, to be aware of these critical aspects is emphasized. The psychological experience of the patient and of his family is thoroughly addressed. Moreover, the complex relationship that developed between the family and the physician as a result of the family's expectations, requests and unconscious projections are discussed. PMID- 2198553 TI - Evaluation of morphological criteria in the cytological diagnosis of thyroid cold nodules. A preliminary study. AB - Although cytological diagnosis plays a significant role in the management of thyroid cold nodules, the rather high rates of false negative cases diminishes its usefulness. The purpose of this preliminary study is to evaluate the utility of numerous morphological criteria used by the cytologist to exclude benign tumours. Thirty-one cytological criteria were routinely scored as binary (yes/no) or as categories: 6 referred to the general arrangement and frequency of thyroid cells, 9 to the associated cellular and cell product elements, and 16 to the morphological features of the cells. We examined the manner in which these criteria, alone or combined, contributed to the diagnosis. The data base consisted of 171 intraoperative imprint cytological samples (143 histologically benign, 1 atypical adenoma and 27 cancers), as well as 257 thyroid cold nodule aspirates from another set of patients (198 histologically benign, 7 atypical adenomas and 52 cancers). For the imprint cytology, the diagnostic power of each criterion was individually assessed by the likelihood ratio (LR) which eliminated 11 as being undiscriminatory. The remaining independent criteria were subjected to logistic regression analysis to determine the most discriminant. Three were selected: Cellular clustering organisation, nuclear hypertrophy and colloid quantity with the latter being somewhat less powerful. Furthermore, it appears that the diagnostic power of the criteria was significantly lower when there was at least one nucleolus (number of nucleoli greater than 0). The smears gave essentially the same results as the imprints.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198552 TI - Genotypic analysis in large cell lymphomas expressing a restricted set of differentiation antigens. AB - Immunophenotyping and immunogenotyping were performed in a series of 8 large cell lymphomas exhibiting anaplastic or "histiocytic" morphology and displaying an uncertain phenotype due to a restricted number of differentiation antigens. 6 cases expressed the Ki-1 antigen. 4 cases expressed one or two B-cell markers and contained rearrangements of the immunoglobulin genes. One of them also exhibited a T-cell receptor (TCR) beta gene rearrangement. 3 cases expressed a single T cell differentiation antigen. Among them, only 1 displayed both gamma and beta TCR gene rearrangement; 1 only contained a gamma TCR gene rearrangement and 1 completely lacked clonal rearrangements. The eight cases expressed an inconclusive immunophenotype due to an abundant population of reactive cells but showed an immunoglobulin gene rearrangement. In conclusion, 5 out of the 8 unusual lymphomas studied here could be characterized by immunogenotyping. This approach was, however, inconclusive in the 3 remaining cases, whose lineage and differentiation stage remain poorly defined. PMID- 2198554 TI - What's new in the role of complement in diseases? AB - The importance of complement in the potentiation of the immune response is now firmly established. More recently, however, evidence has accumulated which suggests that complement may influence biological events following non immunologically mediated tissue damage. Several of the many different genetically controlled structural forms of complement components, which are now recognised, have been shown to influence immunoregulation and disease susceptibility. Furthermore, molecular and genetic analyses have revealed that some of the regulatory elements such as S-protein may have multiple biological functions. As a consequence, it is likely that reference to detailed functional and molecular properties of various complement components, with special reference to regulatory elements will provide new insights into mechanisms of pathogenesis of disease. PMID- 2198555 TI - What's new in the causes of hemorrhage in acute myelogenous leukemia? AB - Hemorrhages in AML are still a major problem, although not the most important and different factors are involved in its genesis. The causes that predispose an AML patient to bleed will be reviewed, the hypotheses concerning the coagulation disorder specially found in the FAB M3 type will be discussed and the increasingly recognized role of plasminogen activators and enzymes released from blasts will be emphasized. PMID- 2198556 TI - [Violence in families and its prevention. Also a plea for abolishing the parental right to inflict physical punishment. A report of the "Violence Commission" of the federal government]. AB - Violence in families is rather frequent. Different forms of violent acts can be distinguished: violence between partners, violence between parents and children, violence among siblings, and violence against elder family members. This report gives an overview--with the emphasis on violence in families--of the work of the "Violence Commission" of the Federal Government. This commission worked out proposals for intervention in the case of intrafamiliar violence as well as for prevention. Two proposals of the commission are explained in detail: (1) Rejection of violence and prohibition of corporal punishment in education and (2) punishability of conjugal violation. PMID- 2198557 TI - Garlic: a review of its relationship to malignant disease. AB - Garlic (Allium sativum) has had an important dietary and medicinal role for centuries. It is now known that garlic contains chemical constituents with antibiotic, lipid-lowering, detoxification, and other medicinal effects in the body. This article reviews some of the physiological characteristics of garlic and examines the relationship between garlic and cancer prevention and treatment. Hypotheses regarding the possible role of garlic in modulating mechanisms that may alter the carcinogenic process are discussed. PMID- 2198558 TI - Measuring the efficacy of psychotropic drugs: clinical symptoms and rating scales. PMID- 2198559 TI - Methodological problems in assessing quality of life as outcome in psychopharmacology: a multiaxial approach. PMID- 2198560 TI - Ascertainment of side effects in psychopharmacologic clinical trials. PMID- 2198561 TI - Diagnoses as selection criteria in drug trials. PMID- 2198562 TI - Functional classification and response to psychotropic drugs. PMID- 2198563 TI - Evaluation of drugs in Alzheimer's disease and age-associated memory impairment. PMID- 2198564 TI - Testing the efficacy of new hypnotic drugs. PMID- 2198565 TI - Placebo-controlled studies in depression: necessity and feasibility. PMID- 2198566 TI - Statistical issues: sample size and dropout. PMID- 2198567 TI - Ribosomes as sensors of heat and cold shock in Escherichia coli. AB - Nearly all cells respond to an increase in temperature by inducing a set of proteins, called heat shock proteins (HSPs). Because a large number of other stress conditions induce the HSPs (or at least the most abundant ones), this response is often termed the universal stress response. However, a careful study of conditions that truly mimic a temperature shift suggested that these proteins are induced in response to a change in the translational capacity of the cell. To test this directly, Escherichia coli cells were treated with antibiotics that target the prokaryotic ribosome. Two-dimensional gels were used to evaluate the ability of these drugs to alter the rate of synthesis of the HSPs. One group of antibiotics induced the HSPs, whereas a second group repressed the HSPs and induced another set of proteins normally induced in response to a cold shock. Depending on the concentration used, the induction of the heat or cold shock proteins mimicked a mild or severe temperature shift. In addition, antibiotics of the cold shock-inducing group were found to block high temperature induction of the HSPs. The results implicate the ribosome as a prokaryotic sensor for the heat and cold shock response networks, a role it may serve in eukaryotes as well. PMID- 2198568 TI - Initial extracellular development in vitro of erythrocytic stages of malaria parasites (Plasmodium falciparum). AB - Merozoites of Plasmodium falciparum placed in culture medium with a 50% erythrocyte extract and supplemented with ATP and pyruvate differentiated extracellularly into early trophic forms. Erythrocyte extract prepared by sonication was found superior to extract prepared by freezing and thawing. Under the best conditions, up to 30% of the merozoites showed some development after 16 hr of incubation and approximately 5% developed into larger forms, often ring shaped and occasionally showing pigment. The small as well as the larger forms took up the fluorescent dye rhodamine 123. Under similar conditions, partial further development was also obtained of young rings freed from their host cells. Again, the sonicated erythrocyte extract gave better development than the frozen thawed extract, and ATP with pyruvate had a marked favorable effect. These parasites had both a plasma membrane and a surrounding closely apposed parasitophorous membrane, whereas the forms derived by extracellular development of merozoites had only their plasma membrane. We conclude that initial development requires neither an intact erythrocyte nor a parasitophorous membrane. PMID- 2198569 TI - Stark spectroscopy of the Rhodobacter sphaeroides reaction center heterodimer mutant. AB - The effect of an electric field has been measured on the absorption spectrum (Stark effect) of the heterodimer mutant (M)H202L of Rhodobacter sphaeroides reaction centers, where the primary electron donor consists of one bacteriochlorophyll alpha and one bacteriopheophytin alpha. The electronic absorption spectrum of the heterodimer mutant from 820-950 nm is relatively featureless in a poly(vinyl alcohol) film, but it exhibits some structure in a glycerol/water glass at 77 K. A feature is seen in the Stark effect spectrum of the heterodimer at 77 K centered at 927 and 936 nm in poly(vinyl alcohol) and a glycerol/water glass, respectively. This feature has approximately the same shape and width as the Stark effect for the primary electron donor of the wild type, which consists of a pair of bacteriochlorophyll alpha molecules. The angle zeta A between the transition moment at the frequency of absorption and the difference dipole delta muA is 36 +/- 2 degrees in the wild type and 32 +/- 2 degrees for that feature in the heterodimer. A range of values for [delta muA] = (13-17)/f Debye units (where f is the local field correction) is obtained for the 936-nm feature in glycerol/water, depending on analysis method. This feature is interpreted as arising from a transition to the lower exciton state of the heterodimer, which is more strongly mixed with a low-lying charge transfer transition than in the wild type. PMID- 2198570 TI - Serum half-life and tumor localization of a chimeric antibody deleted of the CH2 domain and directed against the disialoganglioside GD2. AB - Recombinant techniques allow one to engineer an antibody molecule and, in this way, manipulate its properties and functions. We engineered a chimeric human/mouse antibody to the tumor-associated antigen ganglioside GD2, with the aim of decreasing its serum half-life, maintaining its full antigen-binding capacity, and deleting its effector functions, thus making it a potentially useful reagent for the radioimaging of tumors. To this end, the constant region of the human gamma 1 chain was mutated by deleting the second domain (CH2). Here we show that the CH2-deleted antibody (ch14.18-delta CH2) was cleared from the blood of athymic (nu/nu) mice bearing human melanoma tumors with the same kinetics as human IgG F(ab')2. At a beta t1/2 of 12 hr, 0.9% of the injected dose of 125I-labeled ch14.18-delta CH2 was found per milliliter of blood 24 hr after i.v. injection. In biodistribution experiments, 125I-labeled ch14.18-delta CH2 targeted specifically to melanoma xenografts, achieving optimal tumor-to-tissue ratios 12-16 hr after i.v. injection. ch14.18-delta CH2 was localized to the melanoma tumors more rapidly and with better localization ratios than the intact chimeric antibody ch14.18. Sixteen hours after i.v. injection, the tumor-to-blood and tumor-to-liver ratios of ch14.18-delta CH2 were 5 and 12, respectively, while optimal localization ratios obtained for ch14.18 were 1 and 5, respectively, but 96 hr after injection. A reagent such as ch14.18-delta CH2 should be useful for radioimmunodetection of human tumors because of reduced immunogenicity, increased targeting specificity, and rapid clearance from circulation. PMID- 2198571 TI - The complete coding sequence of arg defines the Abelson subfamily of cytoplasmic tyrosine kinases. AB - We have previously described partial genomic sequences of arg, a human gene related to c-abl, and shown that it is expressed as a 12-kilobase transcript and is located at chromosome position 1q24-25. In this study we elucidate the complete coding sequence of arg by characterization of cDNA clones. Analysis of the predicted amino acid sequence of arg revealed that it is indeed closely related to that of c-abl. The two proteins are strikingly similar with regard to overall structural architecture as well as the amino acid sequences of their tyrosine kinase and src homologous 2 and 3 domains. In addition, arg, like c-abl, is expressed as two transcripts that result from a process of alternative splicing and encode alternative protein forms that differ only in their amino termini. The two genes define the Abelson subfamily of cytoplasmic tyrosine kinases and share a common homolog in Drosophila. PMID- 2198573 TI - Photoreduction of NADP+ by isolated reaction centers of photosystem II: requirement for plastocyanin. AB - The carrier of photosynthetically generated reducing power is the iron-sulfur protein ferredoxin, which provides directly, or via NADP+, reducing equivalents needed for CO2 assimilation and other metabolic reactions in the cell. It is now widely held that, in oxygenic photosynthesis, the generation of reduced ferredoxin-NADP+ requires the collaboration in series of two photosystems: photosystem II (PSII), which energizes electrons to an intermediate reducing potential and transfers them to photosystem I (PSI), which in turn is solely competent to energize electrons to the strong reducing potential required for the reduction of ferredoxin-NADP+ (the Z scheme). This investigation tested the premise of an alternative scheme, which envisions that PSII, without the involvement of PSI, is also capable of photoreducing ferredoxin-NADP+. We report here unexpected findings consistent with the alternative scheme. Isolated PSII reaction centers (completely free of PSI components), when supplemented with ferredoxin, ferredoxin-NADP+ oxidoreductase, and a PSII electron donor,1,5 diphenylcarbazide, gave a significant photoreduction of NADP+. A striking feature of this electron transfer from a PSII donor to the perceived terminal acceptor of PSI was its total dependence on catalytic quantities of plastocyanin, a copper containing electron-transport protein hitherto known only as an electron donor to PSI. PMID- 2198572 TI - Endogenous biosynthesis of arachidonic acid epoxides in humans: increased formation in pregnancy-induced hypertension. AB - Arachidonic acid is metabolized by means of P450 isoenzyme(s) to form epoxyeicosatrienoic acids (EETs) and their corresponding dihydroxy derivatives (DHETs). In the present study, we established the presence in human urine of 8,9 , 11,12-, and 14,15-EETs and their corresponding DHETs by developing quantitative assays and using negative ion, chemical ionization GC/MS and octadeuterated internal standards. Urinary excretion of 8,9- and 11,12-DHET increased in healthy pregnant women compared with nonpregnant female volunteers. By contrast, excretion of 11,12-DHET and 14,15-DHET, but not the 8,9-DHET regioisomer, increased even further in patients with pregnancy-induced hypertension. Intravenous administration of [3H]14,15-EET to three dogs markedly increased its DHET in plasma. The terminal half-life ranged from 7.9-12.3 min and the volume of distribution (3.5-5.3 liters) suggested limited distribution outside the plasma compartment. Negligible radioactivity was detected in urine; this fact infers that under physiological circumstances, urinary DHETs largely derive from the kidney. That P450 metabolites of arachidonic acid are formed in humans supports the hypothesis that these metabolites contribute to the physiological response to normal pregnancy and the pathophysiology of pregnancy-induced hypertension. PMID- 2198574 TI - Enhancement of RNA polymerase binding to promoters by a transcriptional activator, OmpR, in Escherichia coli: its positive and negative effects on transcription. AB - The OmpR binding sequence (OBS) in the upstream region of the ompF promoter of Escherichia coli was fused to 27 synthetic promoters. Transcription from a number of weak promoters, regardless of their sequences, was dramatically activated in the presence of OmpR, a transcriptional activator. In vivo DNA footprinting revealed that OmpR enhanced the binding of RNA polymerase to the promoters. This enhancement was essential for transcription of weak promoters, while OmpR binding to the OBS fused to a strong promoter was inhibitory for transcription. These results indicate that OmpR stabilizes the formation of an RNA polymerase-promoter complex, possibly a closed promoter complex, and that a transcription activator can serve not only as a positive but also as a negative regulator for gene expression. PMID- 2198575 TI - Treatment of Pneumocystis carinii pneumonia with 1,3-beta-glucan synthesis inhibitors. AB - Pneumocystis carinii pneumonia is a major cause of death in AIDS patients in the United States. The presently available treatments have limited use due to a high incidence of adverse reactions. Therefore, there is an urgent need for a safer method for treatment and prevention of this disease. Recent evidence has suggested that P. carinii is related to fungi and that the wall of the cyst form contains 1,3-beta-glucan as a major constituent. Based on this, several proposed 1,3-beta-glucan synthesis inhibitors were evaluated for their ability to control P. carinii pneumonia in vivo. Compounds from two classes of 1,3-beta-glucan synthesis inhibitors, the echinocandins and papulacandins, were found to be effective against P. carinii. PMID- 2198576 TI - Reduced DNA adduct formation in replicating liver cells during continuous feeding of a chemical carcinogen. AB - To investigate early cellular alterations in liver DNA during hepatocarcinogenesis, we have visualized replicating cells and analyzed their DNA adduct content in livers of rats continuously fed a carcinogenic level (0.02%) of 2-acetylaminofluorene for periods up to 4 weeks. One hour prior to sacrifice, cells undergoing DNA synthesis were pulse-labeled with the thymidine analogue 5 bromodeoxyuridine. Replicating cells were visualized immunohistochemically with anti-(5-bromodeoxyuridine), and identification of aminofluorene-DNA adducts in replicating nuclei was achieved by staining with an antiserum specific for N (deoxyguanosin-8-yl)-2-aminofluorene; both stains were observed simultaneously by two-color immunofluorescence. Data were obtained for all cells, including large hepatocytes (nuclei greater than 6 microns) and small cells (nuclei less than 6 microns), such as hepatocytes sliced asymmetrically, oval cells, Kuppfer cells, and sinusoidal lining cells. Based on the size of their nuclei, the hepatocytes were the only cells that could be identified separately from the total. A distinct increase in the number of cells synthesizing DNA was observed after 25 days of 2-acetylaminofluorene feeding; replicating cells were either scattered randomly throughout the liver or clustered in discrete foci. At times up to 28 days, cells with both large and small nuclei that were synthesizing DNA showed reduced aminofluorene-DNA adduct immunofluorescence compared to nonreplicating cells. The results suggest that liver cells replicating during carcinogen exposure have altered metabolic capacities resulting in reduced aminofluorene-DNA adduct formation. It is possible that such cells constitute the progenitors of preneoplastic foci, which have a replicative advantage as compared to normal liver. PMID- 2198578 TI - Relationships between binding, phagocytosis and membrane fusion of enveloped viruses. PMID- 2198579 TI - CD4 inserted in red blood cell membranes or reconstituted in liposome bilayers as a potential therapeutic agent against AIDS. PMID- 2198577 TI - Platelet-derived growth factor stimulates formation of active p21ras.GTP complex in Swiss mouse 3T3 cells. AB - The ras gene product (p21) is a GTP-binding protein and is thought to play an important role in signal transduction of growth and differentiation in many types of mammalian cells. The p21.GTP complex is an active conformation, as described previously for polypeptide chain elongation factors (EF-Tu and EF-G) and heterotrimeric GTP-binding proteins (G proteins). In the study reported here, we measured the amounts of p21-bound guanine nucleotides under various conditions in the G54 cell line, a derivative of Swiss 3T3 cells that overexpresses normal c-Ha ras. More p21.GTP complexes were present in growing cells than in quiescent cells. When quiescent cells were stimulated with fetal bovine serum to promote DNA synthesis, p21.GTP increased approximately 2-fold. Among a number of purified growth factors, platelet-derived growth factor enhanced the formation of p21.GTP, whereas the combination of bombesin and insulin, which also induces DNA synthesis, did not. These results strongly suggest that p21 is a transducer of the growth signal from the platelet-derived growth factor receptor in Swiss 3T3 cells and that the signal is transmitted through a p21.GTP complex. PMID- 2198580 TI - Fusion of human immunodeficiency virus type 1 (HIV-1) with human cells as measured by membrane fluorescence dequenching (DQ) method; roles of HIV-1-cell fusion in AIDS pathogenesis. AB - HIV-1, the primary etiologic agent of AIDS, is a non-transforming human retrovirus which shares many physical and functional characteristics with viruses from the lentivirus family. One of these characteristics is that HIV-1 infection has profound cytopathic effects on host cells. Studies by the membrane fluorescence dequenching (DQ) method using HIV-1 virions labeled with octadecylrhodamine B-chloride (R-18) have shown that HIV-1 enters host cells by a process of fusion between viral envelope and target cell plasma membrane. The parameters of HIV-1-cell fusion are similar to those established for paramyxoviruses and other enveloped fusogenic viruses. HIV-1-cell fusion requires the presence of surface CD4 receptors on human T cell and monocytes, but not on human glial and neuronal cells. It is proposed that cell surface effects of HIV-1 due to the interaction between HIV-1 fusion glycoproteins and membrane receptors are major contributors to the cytopathic and pathogenic function of this virus. PMID- 2198581 TI - Endocytotic processes in the differentiable intestinal cell line HT29. PMID- 2198582 TI - The "microassembly" of integral membrane proteins: applications & implications. AB - We summarize some evidence in favor of the view that the transmembrane region of many, perhaps most integral membrane proteins is made up of an aggregate of hydrophobic alpha-helices, each of which behaves as an autonomous folding domain. Folding of these proteins is seen as a two-stage process during which individual transmembrane helices first form in response to local interactions between the polypeptide and the aqueous and lipid phases, and then pack without extensive rearrangement to yield the three-dimensional structure. This two-stage model is supported by examination of those few structures that are known to a sufficient resolution, by experiments in which functional integral membrane proteins are "microassembled" from separately folded fragments, and by the existence in the inner membranes of organelles of a large number of very small integral subunits, often barely longer than a single transmembrane alpha-helix. We describe application of microassembly to establishing the path of the polypeptide in the tertiary structure of bacteriorhodopsin by neutron diffraction and we briefly discuss its possible role in the biosynthesis of organelle inner membrane complexes and its implications for model building from sequence data. PMID- 2198583 TI - Liposomal MTP-PE for the adjuvant therapy of osteosarcoma. PMID- 2198584 TI - Antibodies to liposomes, phospholipids, and cholesterol: implications for autoimmunity, atherosclerosis, and aging. PMID- 2198585 TI - Membrane electroporation: the dye method to determine the cell membrane conductivity. PMID- 2198586 TI - Liposomes designed to avoid the reticuloendothelial system. AB - Recent work has revealed some new and important characteristics of liposomes: Inclusion of certain glycolipids within liposomes composed of phosphatidylcholine or sphingomyelin and cholesterol drastically prolongs the circulation time and reduces their uptake by liver and spleen. Concomitantly, their accumulation in several implanted tumors is substantially increased. These studies suggest that controlling the circulation time of liposomes and limiting their non-specific uptake by the Reticuloendothelial system (RES) opens up new opportunities for achieving specific targeting to tumors in vivo, with both diagnostic and therapeutic possibilities. PMID- 2198587 TI - Targeted liposomes and intracellular delivery of macromolecules. PMID- 2198588 TI - Endogenous sleep factors: relationships to physiological variables. PMID- 2198589 TI - Role of mammalian hyoid muscles in the maintenance of pharyngeal patency. PMID- 2198590 TI - Role of the genioglossus in periodic breathing during sleep. PMID- 2198592 TI - A method for measuring pharyngeal volumes using magnetic resonance imaging in subjects who snore with and without nasal CPAP. PMID- 2198591 TI - The nature of the wakefulness stimulus for breathing. PMID- 2198593 TI - Multimodality imaging of the upper airway: MRI, MR spectroscopy, and ultrafast X ray CT. PMID- 2198595 TI - Automobile driving in sleep apnea. PMID- 2198594 TI - Suprapontine influences on respiratory patterning during sleep-waking states. PMID- 2198596 TI - Hemodynamics in sleep apnea. PMID- 2198597 TI - Sleep apnea in patients with left ventricular dysfunction: beneficial effects of nasal CPAP. AB - Five patients with congestive heart failure (CHF) and 1 with left ventricular dysfunction but without CHF were found to have sleep apnea. Central sleep apnea (CSA) related to Cheyne-Stokes respiration was seen in 4 cases while obstructive sleep apnea (OSA) was seen in 2. All patients had symptoms of sleep apnea. Nasal continuous positive airway pressure (NCPAP) was effective in reversing CSA and OSA in all patients with improvement in sleep structure and alleviation of symptoms of sleep apnea. In addition, all experienced a reduction in cardiac dyspnea. This was associated with a 5% or greater increase in left ventricular ejection fraction while on NCPAP, compared to baseline value off NCPAP in 5 patients and resolution of chronic pleural effusion and pulmonary edema in the sixth. We conclude that Cheyne-Stokes respiration during sleep may give rise to a CSA syndrome that is reversible by NCPAP. In addition, NCPAP therapy may lead to a reduction in cardiac dyspnea and improvement in left ventricular function in patients with left ventricular dysfunction and sleep apnea. PMID- 2198598 TI - Cardiovascular consequences of sleep apnea. PMID- 2198599 TI - Surgery for obstructive sleep apnea. PMID- 2198600 TI - Comparative physiology of sleep, thermoregulation and metabolism from the perspective of energy conservation. PMID- 2198601 TI - Obstructive sleep apnea syndrome: whom to treat and how to treat. PMID- 2198602 TI - Response of laryngeal mechanoreceptors to transmural pressure: influence of muscle activity and temperature. PMID- 2198603 TI - Postsynaptic control of lumbar motoneurons during the atonia of active sleep. PMID- 2198604 TI - Cardiovascular responses in ageing: a review. PMID- 2198605 TI - Experimental models in skin pharmacology. PMID- 2198606 TI - Selectivity in the inhibition of mammalian cytochromes P-450 by chemical agents. PMID- 2198607 TI - Uses of humor in psychotherapy. AB - Given demonstrated usefulness in facilitating learning, aiding healing, and reducing stress, humor has gained recognition as a clinical tool. This article reviews some uses and potential misuses of humor in psychotherapy and suggests directions for practice and research. PMID- 2198609 TI - Calcium-binding proteins in avian and mammalian central nervous system: localization, development and possible functions. PMID- 2198608 TI - Time courses in visual-information processing: some theoretical considerations. AB - In the literature two different views with regard to the time course of activation of "recognition units"--hypothetical entities that represent identity information--are proposed. Both views are derived from a restricted set of phenomena in visual perception. The first view gets its intuitions from phenomena such as those summarized by Bloch's law; these phenomena show integration or summation of activation over time. This "grow-and-grow" view assumes that recognition units accumulate activation gradually over time. The second view finds its inspiration in phenomena such as Mach-bands and simultaneous contrast; these phenomena show inhibition or steady-state suppression over time. This "grow and-shrink" view assumes that the activation levels increase fast initially and then start to decrease. The perception literature strongly suggests that it may be light intensity that determines whether mainly integration (and phenomena such as Bloch's law) or inhibition (and phenomena such as Mach-bands) is obtained. So it is also likely that both information-processing views apply only to a limited range of intensity conditions; the "grow-and-grow" view to conditions of low light intensities, and the "grow-and-shrink" view to conditions of intermediate- and high-light intensities. It is argued that, to arrive at a complete view, a visual phenomenon that applies to the complete range of light intensities should be taken as a background for generating hypotheses about time courses in visual information processing. The Broca-Sulzer effect is such a phenomenon. Starting from this phenomenon a simple, synthesizing, information-processing model is derived that is compatible with both the "grow-and-grow" view and the "grow-and shrink" view.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198610 TI - Schizophrenia, the history of an illness. PMID- 2198611 TI - Current concepts in the psychosocial management of schizophrenia. PMID- 2198612 TI - Diagnosis of the schizophrenic disorders. PMID- 2198613 TI - Event-related potentials in schizophrenia. PMID- 2198614 TI - Early information processing in schizophrenia. AB - In summary, approaches from various sensory modalities indicate a similar processing deficit for various schizophrenics occurring at approximately 100 milliseconds during or post-stimulus presentation. This deficit occurs during the time period that has been associated with a dysfunctional inhibitory mechanism that is maximally activated during the 100 millisecond time period (e.g., during the period of temporal integration). The inhibitory mechanism is presently conceptualized as being a "transient" or "fast" system involved in the serial/sequential processing of information. The inability of certain schizophrenics to serially process may suggest a dysfunctional inhibitory mechanism for which GABA is a potential candidate. PMID- 2198615 TI - Psychoneuroimmunology: an autoimmune pathogenesis for schizophrenia. PMID- 2198616 TI - Abnormal fluid transport by the epididymis as a cause of obstructive azoospermia. AB - It has been known for more than a decade that in many mammalian species including man, spermatozoa once shed from the testis are immature, immotile and incapable of fertilizing the ovum. During their transit through the epididymis, they undergo various morphological and functional changes that confer on them the ability to ascend the female tract, to undergo an acrosome reaction, to penetrate the zona pellucida and to effect a successful fertilization. By the time spermatozoa have reached the cauda epididymidis, they are held in a quiescent state by factors in the epididymal fluid. The epididymis plays a vital role by creating a favourable fluid environment for sperm maturation and storage. The exact mechanisms underlying sperm maturation and storage are unclear and it appears that no single epididymal factor is held entirely responsible. In contrast, spermatozoa are directly bathed in the epididymal fluid; the fluidity of the microenvironmental has a direct effect on epididymal spermatozoa. The epididymal epithelium has been shown to transport electrolytes and water by processes involving ion pumps, ion carriers and ion channels. These components are under nervous, hormonal and paracrine control and are susceptible to interference by pharmacological agents. This paper reviews the physiology of electrolytes and fluid transport in the epididymis and describes how abnormal fluid transport across the epididymal duct could predispose towards epididymal obstruction, a condition that may occur in cystic fibrosis, Young's syndrome or other unexplained cases of male infertility. PMID- 2198617 TI - Production and regulation of progesterone in bovine corpus luteum and placenta in mid and late gestation: a personal review. AB - In late pregnancy the secretory activity of the corpus luteum of the cow is markedly diminished. This reduced secretion is due to a decline in the number of viable luteal cells as well as reduction in the secretory activity and responsiveness of the cells to trophic agents. The principal extra-ovarian source of progesterone in late gestation appears to be the placenta, especially the fetal cotyledon, which was shown to produce progesterone throughout gestation. Uniquely, this progesterone biosynthesis is cyclic-nucleotide independent, but Ca2+ dependent. It therefore appears that the Ca2(+)-second messenger and protein kinase C systems are responsible for regulation of sterol biosynthesis in the cow placenta. PMID- 2198619 TI - Mechanisms of endometrial bleeding. PMID- 2198618 TI - Steroidogenic cytochrome P450 enzymes and ovarian steroidogenesis. PMID- 2198620 TI - The search for the mammalian testis-determining factor is on again. PMID- 2198621 TI - [Notes for an historical narrative on radiology in Sicily]. PMID- 2198622 TI - [Endorectal echography as a guide to the surgical approach to tumors of the median-lower rectum]. AB - There is no difference in the late results of destructive and conservative surgery in the treatment of rectal cancers, provided that preoperative staging is correct. Thirty-two patients with medium-low rectal cancer underwent endorectal US to evaluate local cancer spread; the aim was allow the correct surgical treatment to be carried out. US findings were compared with pathology: US diagnostic reliability was 93.75%, with 1 case of understaging (T2 as T1) and 1 case of overstaging (T2 as T3). Endorectal US, thanks to its high reliability, is therefore of basic importance because it allows the best local therapy to be chosen and risk margin to be determined. Moreover, US correctly evaluates the degree of parietal infiltration and local spread, thus helping preserve a more or less wide resection margin during destructive surgery. Therefore, endorectal US stands out as a basic research method in the correct preoperative staging of medium-low rectal cancers according to T, thus allowing a rational surgical approach and helping avoid not only unnecessary destructive surgery but also local recurrences. PMID- 2198623 TI - [Portal hypertension of hepatic origin. A qualitative assessment by color and echo Doppler US]. AB - One hundred and twenty-eight subjects were studied: 103 of them were affected with portal hypertension diagnosed both radiologically and clinically. Twenty five healthy subjects were studied, as a control group, by means of combined real time US and color Doppler. US parameters were evaluated, specific to chronic hepatopathy, together with the Doppler qualitative parameters relative to splanchnic vessels hemodynamics. Our results allowed a sort of noninvasive angiogram of the portal system to be obtained, which is to be of use for diagnosing portal hypertension, and for assessing its causes, risks, and consequences. This study was also aimed at suggesting an examination protocol for portal hypertension, employing real-time and color Doppler US, which any radiologist with enough experience in abdominal US could use. Color Doppler, although not strictly necessary to obtain good results, dramatically shortens execution times. Moreover, color Doppler allows the method to be more quickly learned. PMID- 2198624 TI - [Abdominal lymph nodes: the echographic evaluation criteria]. AB - US patterns of abdominal lymph nodes were investigated in patients with neoplastic and non-neoplastic diseases, and in randomly-chosen subjects with no evidence of any pathologic condition. Major longitudinal diameter (DMax) was statistically evaluated, together with minor transverse diameter (DMin), roundness index (RI), and structural index (IS)-i.e., the presence of a central hyperechoic line (as the US sign of normal lymph node architecture). DMax proved to be useless for distinguishing between groups. The presence of a central hyperechoic line was the most useful parameter, although the extant 3 (DMin, RI, IS) were also useful for distinguishing between groups. By correlating each numerical parameter with the hyperechoic line sign an even better discrimination was obtained. Thus, it can be assumed that only a combined and comprehensive evaluation of the above parameters makes the best criterion to differentiate between neoplastic and non-neoplastic abdominal lymph nodes. PMID- 2198625 TI - [CT-guided percutaneous biopsy of adrenal masses. Experience of the technic in 54 neoplasm patients]. AB - Cross-sectional CT and US imaging have allowed the visualization of adrenal glands anatomy and abnormalities. In cancer patients a unilateral or bilateral adrenal enlargement may result from metastasis because the adrenal gland is one of the most common locations for metastasis in thoracic and abdominal tumors. We report our experience in 54 patients who underwent adrenal biopsy for unilateral (44 cases) or bilateral (10 cases) masses during CT examination mostly for lung cancer studies. Twenty-nine of 54 patients (53.7%) had metastatic deposits in the enlarged parenchyma. Other lesions included various pathologic conditions such as primary malignant tumors (2 carcinomas, 2 lymphomas, and 1 pheochromoblastoma) (5.5%), pheochromocytomas (3.7%), nonfunctioning adenomas (14.8%), and simple hyperplasias (12.4%). Eight of 10 patients with bilateral enlargement were metastatic; the extant 2 had simple hyperplasia. Biopsy was useless in 5 cases (9.2%), especially in the beginning and due to poor technique. All procedures were carried out with 18 and 19 G needles and under CT guidance, after standard scanning. The posterior approach was initially used, for both right (15%) and left (7.4%) lesions, but 3 pneumothoraces occurred. At present, we prefer transhepatic approach for the right adrenal gland: this access route is, in our experience, the safest and quickest. Left adrenal masses were approached anteriorly through the left hepatic lobe; when possible, in other patients, we used an oblique posterior transrenal approach, even though macroscopic hematuria occurred in 2 patients, without sequelae. We never used trans-splenic approach, even though this access has been described in literature for pancreatic masses. Transhepatic and transrenal CT-guided biopsy for adrenal masses in cancer patients provides, in our opinion, a correct and unquestionable diagnosis of possible metastasis, also for lesions smaller than 3 cm. PMID- 2198626 TI - [The special "owl's eye" echographic aspect of an aneurysm of the aortic bifurcation]. PMID- 2198627 TI - [Spontaneous urinary extravasation of the contrast medium during urography]. PMID- 2198628 TI - [Schwannoma of the 2d portion of the duodenum: the US and CT aspects]. PMID- 2198629 TI - [Intrascrotal metastases from prostatic carcinoma. A report of a case studied by echography]. PMID- 2198630 TI - [At the roots of the tree of imaging. Notes on the original personalities of radiology]. PMID- 2198631 TI - CT and MR imaging of the central skull base. Part 1: Techniques, embryologic development, and anatomy. AB - Recent advances in surgical techniques have enabled surgeons to approach previously inoperable deep-seated lesions of the skull base. The radiologist requires a thorough knowledge of the normal anatomy and the pathologic spectrum of this region and an understanding of imaging modalities in order to determine the extent of pathologic conditions and help plan the surgical approach. The embryologic development of the central skull base, normal gross anatomy, and anatomy as seen on computed tomographic and magnetic resonance images are presented. PMID- 2198632 TI - CT of malignant melanoma in the chest, abdomen, and musculoskeletal system. AB - Malignant melanoma is an aggressive neoplasm that can involve virtually every organ system. This article provides a review of the various appearances on computed tomographic (CT) scans of melanoma involving the chest, abdomen, and musculoskeletal system. Specific emphasis is placed on the typical and atypical CT manifestations of disease as well as the similarity of these findings to those for other disease entities. The importance of accurate staging of melanoma is stressed. PMID- 2198633 TI - Acute abdomen in AIDS: CT diagnosis and triage. AB - Computed tomographic (CT) scans of 80 patients with acquired immunodeficiency syndrome (AIDS) and acute abdominal pain were reviewed for the purpose of highlighting the use of CT in diagnosis and triage. Common and uncommon causes of acute abdominal pain in patients with AIDS are discussed and their CT findings illustrated. Clinical case histories demonstrate how CT can be used to quickly narrow diagnostic possibilities to perform triage between surgical and nonsurgical management and to further direct diagnostic workup. PMID- 2198634 TI - Sonography of complications in pediatric renal allografts. AB - A total of 420 sonograms of renal transplants in 80 children were obtained because of decreased renal function or to establish a baseline after surgery. We describe normal anatomy of a renal transplant on sonograms, including duplex Doppler and color flow images, and a spectrum of complications. The complications are categorized as follows: parenchymal (drug toxicity rejection, acute tubular necrosis, infection), vascular (pseudoaneurysm, arteriovenous fistula, renal artery stenosis and occlusion), obstructive uropathy, and postoperative fluid collections. PMID- 2198635 TI - [Captopril in single doses in the treatment mild-moderated arterial hypertension]. AB - The effect of single dose (50 mg) Captopril (C) used either alone or associated to diuretics (50 mg hydrochlorothiazide -HCTI) in the treatment of mild-moderate essential arterial hypertension was studied in a multicentric study. Eighty eight patients were chosen. After a minimum of 4 month follow-up period 53.4% responded (BDP less than 95 mm Hg) to single dose C (group 1:47 patients), 89.77% to 50 mg C in single dose together with 50 mg HTIT (group 2: 32 patients), 95.45% of two 50 mg doses of C and 50 mg HCIT (group 3: 5 patients), and 97.72% responded to 3 doses of C and 50 mg of HCTI (group 4: 2 patients). The decrease in blood pressure values was statistically significant (p, 000, Wilcoxon test) in groups 1 and 2, having a mean decrease in blood pressure (BP) of 14%. In group 1 (n = 42) the SBP which initially was 165.72 +/- 11.32, decreased to 148.28 +/- 11.5 and the DBP decreased from 101.55 +/- 5.68 to 87.28 +/- 6.59. In group 2 (n = 32) the SBP decreased from 173.50 +/- 14.08 to 152.44 +/- 20.8 and the DBP from 103.34 +/ 5.29 to 87.47 +/- 6.39. The response to monotherapy could not be statistically correlated either to early essential hypertension or to the patients age. Treatment was discontinued in three cases due to the secondary effects, cough, ageusia and nervousness, showing the remaining patients a good tolerance. No changes were observed in the analytical parameters. This study shows the usefulness and tolerance of single dose C as the initial treatment of mild to moderate essential hypertension. PMID- 2198636 TI - [Prevalence, physiopathology and processes associated with hypouricemia in a hospitalized population: analysis of 27,987 analytic determinations]. AB - A prospective analysis of 27,987 serum samples revealed a uricemia less than 2.0 mg/dl in 172 patients (prevalence of 0.61%). One hundred and six patients were being treated with more than one drug. Amongst the 21 hypouricemic patients receiving only one drug the more frequently associated drugs were beta lactamases, salicylates at high doses, and carbamazepine. Out of the 45 hypouricemic patients who were under no treatment, there were 12 cases of pregnancies, 6 had a neoplastic disease, 2 suffered chronic hepatopathy and one presented hereditary xanthinuria. Out of 7 non treated patients, 6 were uric acid hypersecretors and only one was hyposecretor. The results indicate that hypouricemia: a) is usually associated with an elevated renal excretion of uric acid and b) it is frequently associated with the administration of drugs although it can also be included in the context of multiple systemic disease. PMID- 2198637 TI - [Pseudothrombocytopenia. A medical problem stemmed from a technical advance]. PMID- 2198638 TI - [The right ventricle and pulmonary circulation in hypertensive patients]. AB - Elevated blood pressure and vascular resistance in patients with systemic hypertension are paralleled by a proportional rise in pressure and resistance in the lesser circulation. It was hypothesized that increased systemic reaction to adrenergic stimulation is shared by the pulmonary vessels. Thus normotensive subjects and patients with primary hypertension were investigated during mental arithmetic and the cold pressor test. Both groups responded to both stimuli; during arithmetic pressure reaction was mediated through an increase of cardiac output, and during the cold pressor test through a predominant rise in systemic vascular resistance. The pressure changes were emphasized in the hypertensive population. Pressure in the pulmonary artery in normotensive subjects was not affected by cold and was slightly raised (systolic) during arithmetic. In hypertensive patients, on the other hand, systolic and diastolic pressures were consistently augmented by both tests, and pulmonary arteriolar resistance rose by 42% and 29% of control during the cold pressor test and arithmetic, respectively. Changes in resistance reflected neurally-mediated vasoconstriction but not variations in the passive relationship between pressure and flow, since during arithmetic, for a similar rise in flow the driving pressure across the lungs was steady in normotensive subjects and rose significantly in hypertensive patients. In these same patients pressure was augmented by cold test in the absence of substantial changes in flow. At baseline and during tests pulmonary wedge pressure, pleural pressure, arterial blood gases, and pH were similar in the two populations. The intravenous infusion of similar scalar doses of norepinephrine (the same mediator released during cold test) was not effective on the pulmonary vessels of normotensives and caused an obvious vasoconstriction in hypertensives.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198639 TI - [Heart aging and its clinical implications]. AB - Aging-induced cardiac modifications are almost never different--at least qualitatively--from those linked to chronic pathologies that are usually found in advanced age. Due to many factors, as myocyte hypertrophy, increase in the amount of collagen and subepicardial fat accumulation, the aging heart increases its own weight. All cardiac structures undergo regressive modifications: valvular apparatus show fibrosis, collagen fragmentation, lipid accumulation and calcifications, the coronary arteries are characterized by tortuosity, minimal atherosclerotic lesions, calcium precipitates and--at least in animals--by an imbalance between the capillary bed extension and the myocyte hypertrophy. The most peculiar changes of interstitium, aside from fibrosis, are represented by lipofuscins and amyloid deposits. From a functional point of view, the aging heart does not show any substantial difference from the adult one in the basal state. Cardiac output seems to be maintained during exercise in the elderly. Nevertheless, such a result is achieved by an end-diastolic volume increase, instead of positive chronotropic and inotropic response and to the peripheral resistance decrease of the younger. This could be partly due to a damped cardiovascular response to sympathetic beta-receptor stimulation. The diastolic phase undergoes a progressive dysfunction, as its duration increases, the early filling falls and the atrial contribution plays a major role. The reduction of many mitochondrial enzymatic processes--such as fatty acid oxidation and oxidative phosphorylation--has been documented in animals, as well as transmembrane ionic fluxes alteration. The maximal oxygen consumption is progressively reduced, although this does not seem to be due to a cardiac performance impairment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198640 TI - Coronary atherosclerosis and thrombosis. AB - The relationship of thrombus to atherosclerosis is complex and far more wide reaching than the obvious causal association of a thrombotic occlusion in a coronary artery with myocardial infarction. An atherosclerotic plaque may be eccentric (localized primarily along one segment of the arterial wall) or concentric (localized circumferentially) and is a complex structure composed of connective tissue, calcium, inflammatory cells and lipid in proportions differing from plaque to plaque. The consistency of plaques depends on the proportion of their component elements: a heavily fibrotic and calcified plaque is hard, whereas a plaque composed predominantly of cholesterol-ester and lipid-containing macrophages is soft. Plaques with a soft lipid core may be covered by a relatively thin cap of fibrous connective tissue separating the plaque material from the luminal blood flow. A rupture or fissure of this cap allows blood to enter the plaque causing dissection of its structure and deposition of fibrin in the plaque. Fissuring commonly promotes thrombosis also in the lumen of the artery and may be followed by thrombus fragmentation and embolization. Mural thrombi may wax and wane, causing intermittent occlusions and fleeting, minor clinical symptoms. Further episodes of thrombosis increase the mass of the mural thrombus in the already restricted lumen and may herald the onset of ischemic symptoms, abruptly aggravate a stable clinical state and produce the crescendo type of unstable angina, dysrhythmias, myocardial infarction or sudden coronary death. The episodic dynamic progress of atherosclerotic disease and local thrombosis governs the episodic evolution of the clinical course. PMID- 2198641 TI - [Monitoring of respiratory exchange during ergometric test in patients with heart failure: current aspects and prospects]. AB - The current techniques of respiratory gas-exchange monitoring during stress testing in patients with congestive heart failure have provided new physiopathologic and clinical data. The "breath-by-breath" measurement of oxygen consumption and carbon dioxide production and the evaluation of the relationship between these parameters and respiratory volumes, allow to determine both ventilatory and metabolic responses during exercise, thus giving a precise estimate of the effective cardiopulmonary functional capacity. The demonstration of peripheral vascular and metabolic abnormalities by these techniques have provided new insights into the mechanism of dyspnea and fatigue in patients with heart failure. Although the relationship between respiratory and metabolic parameters and hemodynamics has been extensively studied, its mechanisms are still unclear. Moreover, controversy still exists as to the link between functional capacity and prognosis. Finally, recent studies on the cardiopulmonary adaptations to exercise training in patients with left ventricular dysfunction, have clearly demonstrated clinical and hemodynamic improvement after conditioning. These data, if confirmed, may provide a new approach in the management of patients with this disorder. PMID- 2198642 TI - [Clinical usefulness of non-invasive automatic monitoring of arterial blood pressure]. AB - Recently, new devices for ambulatory blood pressure monitoring have been developed, which have become widely used as highly reliable diagnostic tools. It is now necessary to establish the rationale for their use, and to fully elucidate the diagnostic, prognostic and therapeutic advantages for their use in hypertensive patients. Average 24-hour blood pressure is more closely correlated with the degree of structural cardiovascular alterations than casual blood pressure measurements. Non-invasive blood pressure monitoring therefore seems to be more useful, from a prognostic point of view, than traditional, sphygmomanometric measurement. There is some evidence that ambulatory blood pressure monitoring is more reliable than casual measurements in assessing the efficacy of antihypertensive therapy. From a diagnostic point of view, the significance of blood pressure values obtained with these devices, and the most appropriate index to evaluate the 24-hour blood pressure load remain to be clarified. It is necessary to identify new normal limits for monitored blood pressure values i.e. to establish the baseline level for the start of treatment. At present, due to the lack of widely accepted upper limits of monitored blood pressure, the therapeutic decision should be based on casual blood pressure values, obtained with traditional mercury sphygmomanometer. PMID- 2198643 TI - [Physiology of fibrinolysis and thrombolytic agents]. AB - We briefly summarize the physiology of fibrinolysis, with particular regard to structure and function of its most important activators, zymogens, enzymes, inhibitors and co-factors. Thrombolytic drug action, the dose commonly used and the main clinical indications, as reported in the literature, are described. PMID- 2198644 TI - [Thrombolytic therapy in acute myocardial infarct]. AB - All thrombolytic agents convert plasminogen to plasmin, either directly as urokinase, saruplase and alteplase or indirectly as streptokinase. In the majority of recent clinical trials with streptokinase, a high-dose (0.7 to 1.5 mega-units), brief-duration (30 to 90 minutes) drug regimen has been used. After a mean time interval of 4.2 hours from onset of pain to intravenous infusion of streptokinase, a repeat angiography performed 60 to 90 min after start of thrombolytic treatment gives a reperfusion rate of 43%, the corresponding figures for anistreplase, saruplase and alteplase are 56%, 67% and 69%. The patency rates of similar studies with the same endpoint are for streptokinase 56%, for anistreplase 77%, for urokinase 62%, for saruplase 71% and for alteplase 75%. The reduction in hospital mortality in randomized trials with intravenous streptokinase (high-dose) is in 6 large studies in a total of 23,267 randomized patients from 10.7% in the control group to 7.0% in the streptokinase group. In a mortality study involving 1,004 patients randomized to intravenous anistreplase or placebo the 30-day mortality was reduced by 47%, from 12.2% to 6.4%. A large trial in which 5,011 patients were randomized to alteplase or placebo, the 30-day mortality was 7.2% compared to 9.8% in controls, a reduction of 27% by alteplase. In another trial 721 patients were randomized to placebo or alteplase; all patients were on aspirin. The 14-day mortality was only 2.8%, 51% less than that in the control group. It is most important that the favourable impact on hospital survival is maintained at 1 year with any thrombolytic drug. Large scale trials directly comparing mortality after alteplase, streptokinase or anistreplase are being performed or in the planning phase. The risk of bleeding exists with any thrombolytic agent but intracranial bleeding is the most serious one. In a large trial on 5,011 patients with acute myocardial infarction, stroke occurred in 1.1% of alteplase treated patients compared with 1.0% in placebo treated controls. Crucial problems are residual stenosis of the coronary artery and reocclusion. Urgent angioplasty does not seem to be the right answer; more effective antithrombotic strategies still have to be developed. PMID- 2198645 TI - Autosomal mendelian disorders and microcytogenetics. AB - The development of cytogenetic high resolution banding techniques has allowed the observation of specific chromosome rearrangements--i.e. microdeletions, translocations--in patients with morbid conditions suspected to have a genetic component but for which a precise etiology had not, or rarely, been recognized. The most striking examples are retinoblastoma, the WAGR complex, Beckwith Wiedemann syndrome, Langer-Giedion syndrome, Prader-Willi syndrome, Miller-Dieker syndrome and others, which thus could be mapped to the genome. Molecular technology further allowed in a number of cases cloning of the genes proper or of linked DNA polymorphisms permitting genetic counseling. PMID- 2198646 TI - [Role of magnetic resonance spectroscopy in the diagnosis of ischemic cerebrovasculopathy]. AB - NMR is still considered essentially, in the field of ischemic brain vascular disease, an imaging method. On the contrary, Authors review MR-spectroscopy possibilities, emphasizing that by this method it is possible to achieve a complete and dynamic study of brain energy metabolism, and therefore to identify markers of cellular injury clearly more sensitive and precocious than MRI morphological findings. Moreover, this method allows to easily evaluate cerebral blood flow, pharmacologic treatment efficacy, effects of eventual metabolic abnormalities on ischemia's evolution. PMID- 2198647 TI - [Liver and thyroid gland. Physiopathologic and clinical relationships]. AB - The liver plays a dominant role in the metabolism of the thyroidal hormones; it is here that the 5' deiodase acts to convert part of T4 to T3. There are eight further circulating iodothyronines: the rT3, mainly derived from T4, appears to be the major inhibitor of T4 and T3. Thus, if rT3 increases, the metabolic effects of T3 and T4 can be quite different. In the course of some chronic systemic diseases (e.g. hepatic cirrhosis) rT3 increases simultaneously with the decrease of T3 levels. Therefore we can describe particular alterations of the thyroidal pattern typical of chronic liver diseases: low T3 syndrome, low T3 and T4 syndrome, high T4 syndrome, mixed forms. T3 and T4 diminish due to inefficient hepatic deiodination and defective hepatocellular uptake. Inefficient hepatic deiodination and defective hepatocellular uptake. T4 levels decrease, most likely because of an inefficient production of thyroid binding globulin, or the action of a peripheral binding inhibitor. During acute liver diseases and primitive biliary cirrhosis, we can observe an increase of T4 and TBG together with an increase of the acute phase proteins. Such complex hormonal mechanisms are not influenced by TSH, which appears normal or inhibited, as the TRH stimulus test is normal. The explication can be found in an enhanced conversion of T4 to T3 in the pituitary gland. The biological and clinical significance of these mechanisms might be that of creating a "protective" state for an organism in a catabolic state by reducing the circulating T3. A relationship has been found between circulating thyroidal hormones levels, particularly the T3, rT3 and rT3/T3 ratio, and the state of hepatic functional insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198648 TI - [ Physiopathology and treatment of accidental hypothermia]. AB - Severe hypothermia is seldom observed in our country due to the mild climate. But it can represent a difficult medical problem. Severe hypothermia occurs when body temperature falls below 28 degrees. The victim may be unconscious with a severe depression of vital functions. All such patients should undergo vigorous cardiopulmonary resuscitation and rapid rewarming. The most efficient methods of rewarming are represented by peritoneal irrigation and esophageal thermal tube. PMID- 2198649 TI - [Lung cancer, diet and nutrition]. PMID- 2198650 TI - [Clinical studies of interleukin-2]. PMID- 2198651 TI - [Systemic lupus erythematosus and pregnancy]. PMID- 2198652 TI - [Kashin-Bek disease]. PMID- 2198653 TI - [Diabetes mellitus: a challenge in primary health care]. PMID- 2198654 TI - [The marginal adaptation of mechanically produced onlays in vitro]. AB - In this study, 24 extracted human molars were restored with onlays fabricated by using the Cerec System. The teeth were divided into 4 groups: in groups 1, 2 and 3 the proximal cervical margin was located coronally to the CEJ so that enamel was still present; in group 4 the proximal cervical margin was located in dentin. Vita-Cerec porcelain was the restorative material in groups 1 and 4; compressed HT-Hybrid composite in group 2 and glass-ceramic in group 3. Marginal adaptation of the onlays was examined by SEM before and after a combined occlusal loading and thermocycling test (72.5 N, 500,000X, 1.6 Hz; 1250X 5 degrees C - 55 degrees C - 5 degrees C, 4 minutes interval). In addition, a dye-penetration test was performed. The SEM evaluation and the penetration test revealed marginal adaptation values of the composite-luting agent both to enamel and the three restorative materials close to 100%. Marginal adaptation scores did not differ between porcelain, glass-ceramic and HT-composite and the three materials were equally adequate for being used with the Cerec method. PMID- 2198655 TI - [Implant-bearing crowns and bridges. The indications, therapeutic planning and crown-bridge prosthetic aspects]. PMID- 2198656 TI - Oravske kuru. A human dementia raises the stakes in mad cow disease. PMID- 2198657 TI - Profile: gene doctor. W. French Anderson pioneers gene therapy. PMID- 2198658 TI - The Salk Institute at a crossroads. PMID- 2198659 TI - Overview of myeloid growth factors. AB - Initial steps in dissecting the regulatory influences on the process of hematopoiesis have involved the characterization of humoral modulators able to stimulate in vitro colony formation by myeloid progenitors. Several colony stimulating factors (CSFs) have been molecularly characterized and produced in quantity through the use of recombinant DNA technology. Investigation of the myeloid CSFs indicate that they are potent stimulators of the production of mature neutrophils, monocytes, eosinophils, and, in some cases, augment platelets and red cell elaboration. CSFs also have important direct effects on mature circulating leukocytes. Granulocyte-CSF and granulocyte-macrophage-CSF prime neutrophils for enhanced function including enhanced oxidative metabolism, phagocytosis, and cytotoxicity. Granulocyte-macrophage colony-stimulating factor and interleukin-3 have stimulatory action on eosinophils and macrophages while the effects of macrophage-CSF appear to be limited to cells of the mononuclear phagocyte series. The development of the myeloid growth factors as therapeutic agents offers the prospect of unique strategies for enhancing overall host defense. Results of clinical trials with some of these factors suggest beneficial effects in a variety of settings. PMID- 2198660 TI - Effects of granulocyte-macrophage colony-stimulating factor in iatrogenic myelosuppression, bone marrow failure, and regulation of host defense. AB - In early studies, recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) has been found to reduce the depth and duration of granulocytopenia in the settings of cancer chemotherapy and autologous bone marrow transplantation. In patients with myelodysplastic syndrome or aplastic anemia. GM-CSF has produced increased marrow cellularity and marked leukocyte responses, and multilineage effects have been observed in some patients. The available data suggest that the use of GM-CSF in these settings is associated with a decreased incidence of infection as compared with that in historical controls or pretreatment periods and that it may enhance the ability to deliver optimal doses of cancer chemotherapy. Other findings suggest that GM-CSF may be useful in regulating host response to infection when used in combination with antimicrobial therapy in neutropenic patients. However, a precise determination of the ability of this agent to significantly affect patient morbidity or mortality in these various contexts awaits the results of larger, longer-term, randomized, controlled trials. PMID- 2198661 TI - Erythropoietin: physiology and clinical experience. AB - Erythropoietin is a glycoprotein hormone of primarily renal origin that promotes the proliferation and differentiation of erythrocyte precursors. Technological advances have resulted in the production of recombinant hormone suitable for therapeutic use and have permitted significant progress in the characterization of the physiologic and pathologic processes involved in endogenous erythropoietin production. In situ hybridization studies have shown that erythropoietin production in the hypoxic kidney occurs primarily in peritubular cells, most likely endothelial cells. In renal carcinoma associated with polycythemia, however, erythropoietin mRNA has been detected in the tumor cells, which are tubular in origin. New information regarding the biochemistry of the erythropoietin receptor has been gleaned subsequent to the cloning of the gene encoding the receptor; however, much remains to be learned about the interaction of the hormone with its target cells. With regard to clinical experience, recombinant erythropoietin has been shown to correct the anemia associated with chronic renal failure in patients requiring dialysis, having a significant beneficial effect on the overall physical and psychological state of the patient; the major adverse effect of such treatment is hypertension. The role of recombinant erythropoietin in predialysis patients, patients with anemias of other origin, and other clinical settings is currently being evaluated. PMID- 2198662 TI - Granulocyte-macrophage colony-stimulating factor in human immunodeficiency virus disease. AB - Factors contributing to the development of cytopenias in patients with advanced human immunodeficiency virus (HIV) disease include primary HIV-related suppression of blood cell production, opportunistic infections and neoplasms that directly involve the marrow cavity, and the toxicity of antiviral, antiinfective, and antineoplastic therapy. Indeed, bone marrow toxicity is often the complication limiting delivery of effective therapy in such patients. Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to increase the leukocyte count in this patient population. Although there is concern that GM-CSF administration may increase HIV replication in myeloid cells, this effect has not been observed in clinical studies. In addition, the most appropriate use of hematopoietic growth factors would be in combination with effective antiretroviral agents, such as zidovudine. A pharmacologic basis for such combination is provided by the finding that inhibition of HIV by zidovudine may be augmented by GM-CSF. It recently has been shown that patients with severe leukopenia and intolerance to zidovudine can have reconstitution of effective myelopoiesis with low doses of subcutaneously self-administered GM-CSF and become hematologically tolerant of zidovudine 1,200 mg/d. The major adverse effects of this combination regimen were constitutional symptoms and thrombocytopenia. Further investigation of GM-CSF and other hematopoietic growth factors in this patient population is warranted. PMID- 2198663 TI - Osteoarthritis: a review of old myths and current concepts. AB - Radiology is dependent on an accurate understanding of the pathological process. This review of primary osteoarthritis identifies eight areas in which widely held concepts are either demonstrably false or fall short of proof. In some, the concepts have been disproved by the gradual accumulation of evidence. In others, the error is due to radiological misinterpretation while in a third group, the evidence is not in dispute, but the logical framework used in its assessment is flawed. Awareness of these deficiencies simplifies radiological interpretation and clarifies research objectives. PMID- 2198664 TI - [Anorexia nervosa. A specific eating disorder]. PMID- 2198665 TI - Molecular genetics of signal transduction by muscarinic acetylcholine receptors. PMID- 2198666 TI - Structure/function relationships of ras and guanosine triphosphatase-activating protein. PMID- 2198667 TI - The impact of the fee-for-service reimbursement system on the utilisation of health services. Part I. A review of the determinants of doctors' practice patterns. AB - The impact of different methods of reimbursement on the practice patterns of doctors has received little attention in the local literature. This series of three papers attempts to address this gap. Here the international evidence on this issue is reviewed. The 'information gap' between doctors and their patients allows doctors to induce demand for their services. This leads to the potential for doctors to increase the supply of services when they stand to gain financially from doing so, as is the case in the fee-for-service system. There is extensive international evidence, at both national and micro levels, of the link between increased utilisation and the fee-for-service payment system. This is in contrast with the pattern noted in the salary system, used in some health maintenance organisations (HMOs) in the USA, or in the capitation system, used in the British National Health Service. The 'practice setting' in which doctors operate also affects patterns of practice. In the local fee-for-service sector, 'third-party payment' means that both doctors and patients have little awareness of the direct costs of services. In other systems, such as HMOs, there is a strong cost consciousness on the part of practitioners. These differences in practice setting account in part for the different patterns of utilisation in these systems. The fee-for-service system, as it is structured in South Africa, thus leads to extreme inefficiency, and the development of alternatives is becoming an urgent necessity. All systems of reimbursement have certain problems, and some combination may be the best solution. PMID- 2198668 TI - [Methods of breast disease diagnosis. Value and limits]. PMID- 2198669 TI - [Breast diseases. Radio-echo-histological correlations]. PMID- 2198671 TI - Nondiscrimination: the enemy is us. PMID- 2198670 TI - [Description of tooth morphology by Jacob Winslow, 1732]. AB - J.W. was the author of Exposition Anatomique de la Structure du Corpses Humain" which was published in 1732. The translation into Danish was used as a basis for this article. It describes Winslow's impact on the understanding of the morfology of the human dentition. A short description of Winslow's work in other fields of anatomy is also given. PMID- 2198672 TI - 'Safe harbors' protect physicians from the Medicare storm. PMID- 2198673 TI - Texas physicians fare poorly with geographic practice cost index. AB - Big changes in the way Medicare pays physicians are coming, thanks to the Omnibus Budget Reconciliation Act of 1989 (OBRA). TMA is monitoring and participating in the plans for those changes. Beginning in 1992, a new fee schedule-based payment system will be phased in over the following 5 years. The Medicare Fee Schedule will be based on three components: the Resource Based Relative Value Scale (RBRVS), a conversion factor, and a geographic adjustment factor, known as the geographic practice cost index (GPCI). In this special section on GPCIs, three experts discuss the effect the GPCIs may have on Texas physicians. PMID- 2198674 TI - Searching for equal pay for equal service. PMID- 2198675 TI - TMA seeks fairness in physician payment reform. PMID- 2198676 TI - Andrology today. AB - Andrology is an interdisciplinary field of medicine which developed in the second half of this century. Schirren was the first one to use this term. In Hungary, andrology was established by Jeno Molnar. Certain question of topical interest of andrology are discussed in the present study. Besides the endocrinologically well definable male hypogonadism caused by primary lesions of the hypothalamus pituitary-testis-androgen periphery system andrological anomalies of known or unknown origin also occur in a great number of cases. As collective designation the use of "consecutive hypogonadisms" is recommended for these conditions. Other endocrine and non-endocrine disturbances, injuries of the male gonad system caused by drug therapy, environmental noxa and unknown factors may be ranged also into this group. In vitro fertilization applied in certain cases of infertility and cryostorage of human embryo pose several problems even to the andrologist. The development of an effective and harmless male contraceptive has to be realized in the future. The diagnosis of male climacteric may be assessed only after excluding other diseases. For the treatment of this condition low doses of androgen preparations are recommended. PMID- 2198677 TI - Loperamide (imodium)--clinical trial. AB - 1. Imodium (loperamide) produced by Chemical Works of Gedeon Richter, Budapest, is a useful preparation for the symptomatic treatment of both acute and chronic diarrhoea of various etiologies. 2. In chronic diarrhoea cases the best results were obtained in the treatment of functional disorders of the guts. 3. Side effects occurred only in few patients and with low intensity, the treatment had to be interrupted in none of the cases. PMID- 2198679 TI - Stages of the development of the electron microscope. PMID- 2198678 TI - Use of tensiomin (captopril) in the antihypertensive treatment of haemodialysis patients. AB - The observations of a 16-week Tensiomin therapy of 10 hypertensive patients treated with hemodialysis have been discussed. The patients have been treated for about 5 years with hemodialysis, suffered from anuria and required besides systhematical ultrafiltration a combination antihypertensive therapy. Tensiomin was combined with Minipress, Trasicor, Depressan, Estulic and Corinfar by using three- or four-drug combinations. In the course of the administration of Tensiomin the doses of the other antihypertensive drugs could be decreased by 50% on average, while the blood pressure of the patients was normalized. By controlling the patients on weeks 1, 4, 12 and 16 of therapy toxic side-effects or notable pathological changes of the examined laboratory parameters (WBC, serum total protein, Na, K, Ca, P, bilirubin, blood sugar and SGOT values) were not seen. It has been concluded that Tensiomin is an effective drug in combination therapy applied for normalizing the hypertension of dialysed patients. PMID- 2198680 TI - [Meaningful combinations of chemotherapeutic agents]. AB - It is frequently assumed that, in general, combinations of antibiotics and similar chemotherapeutic agents are more efficient than the single chemotherapeutic, and that they can be combined without disadvantages for the activity of the single component. However, the specific properties of the combined substances, such as their antimicrobial spectrum and resistance, their pharmacokinetics and side effects, as well as their physical properties and formulation, have an enormous impact on the activity of combined chemotherapeutics. They may lead to an advantageous, but also to an indifferent or diminished activity of the combination in patients. Some of the important requirements for an advantageous combination of antibiotics and similarly functioning compounds will be reviewed and ways of avoiding mistakes are described. PMID- 2198681 TI - [Recent information on tick-borne diseases (II)]. AB - Tick-borne encephalitis (central european encephalitis) and Lyme disease (erythema chronicum migrans) are diseases mainly transmitted by ticks of the ixodus ricinus species. The tick-borne encephalitis, a virus infection, can produce severe encephalitic symptoms. There is no specific treatment but the infection can be prevented by active or passive immunization. Lyme disease is caused by a spirochete (borrelia burgdorferi). Due to the variety of often uncharacteristic symptoms this infection is not easily recognized. However, early diagnosis and antibiotic treatment are necessary to prevent chronic damage to skin, joints, heart or nervous system. PMID- 2198682 TI - [Parasitic diseases in sheep and goats in Germany]. AB - A review is presented on the species spectrum, biology and epidemiology of endo- and ectoparasites of sheep and goats in Germany. Current therapeutic, prophylactic and metaphylactic measures are given and discussed. PMID- 2198684 TI - Pulmonary toxicity of inhaled and intravenous talc. AB - Talc (magnesium silicate) is a widely used, generally considered benign substance. It is principally used as an inert filler material in drug tablets or as a drying ingredient in baby powders. However, in both cases inappropriate use can lead to severe pulmonary toxicological responses. On the one hand, intravenous injection of 'solubilized', CNS active pills can produce microemboli in small pulmonary vessels. This can lead to various degrees of granuloma formation, compromised pulmonary function, or death. Overzealous application of baby powder can also produce severe pulmonary complications if the infant inspires the powder. Although the data are relatively scarce, a number of reports suggest the existence of a chronic problem in this area. PMID- 2198683 TI - [Clinical diagnosis and differential diagnosis in ornamental birds]. AB - Clinical diagnosis in companion birds consists of well established procedures such as case history, clinical observation, physical examination and further special investigations, e.g. radiology, endoscopy or clinical chemistry. Also some peculiarities of the numerous bird species have to be taken into consideration. These are, for example, certain characteristics of the different species, the varieties of husbandry and environment as single caged birds or flocks in zoos and aviaries and, especially, the lack of typical clinical symptoms in most cases. In regard to those aspects, case history concerning aspects such as age, sex, feeding or course of the disease and special investigations in the case of single caged birds and diagnostic dissections and etiological laboratory examinations, e.g. microbiology, parasitology and toxicology, in the case of flock problems are of major significance. Examples of differential diagnosis in single caged birds, e.g. abnormal behaviour ("feather plucking"), gout, intestinal foreign bodies, tumors or pneumomycosis, and flock health problems, e.g. acariasis, canary pox, coccidiosis or bacterial infections complete this paper. PMID- 2198685 TI - Pharmacologic agents in the management of bleeding disorders. PMID- 2198686 TI - [The possibility for studying the ischemia of the optic disk in primary open angle glaucoma]. AB - The suggested quantitative method for the assessment of the microcirculation in the anterior segment of the optic disk in the patients with primary open-angle glaucoma has revealed reduced local and total fluorescence of the optic disk vascular net, this reduction augmenting with the disease progress and indicating an ischemic type of the optic disk impairment. Rationale for the use of the suggested method for the diagnosis of open-angle glaucoma is given. PMID- 2198687 TI - [The prevention of the transmission of the human immunodeficiency virus in ophthalmological practice]. PMID- 2198688 TI - [Jan Evangelista Purkinje and ophthalmology]. PMID- 2198689 TI - Multidisciplinary team dismisses BSE 'threat'. PMID- 2198690 TI - [The oncological aspects of infection caused by the human immunodeficiency virus]. PMID- 2198691 TI - [Puncture biopsy with ultrasonic control in the diagnosis of space-occupying lesions of the organs of the abdominal cavity and lesser pelvis]. AB - Fine-needle puncture aspiration biopsy was performed in 182 patients with various visceral tumors. The results were negative in 4 (2.2%) cases only. The malignant nature of tumor was established in 140 cases whereas benign--in 38. The histogenetic type of tumor was reliably established in 75% of patients. In 25% of cases, biopsy revealed a malignancy but failed to identify its origin. PMID- 2198692 TI - [The antitumor effect of Baikal skullcap]. PMID- 2198693 TI - [The history of oncology in postage stamps]. PMID- 2198694 TI - [The epidemiological problems of the vitamin prophylaxis of cancer]. PMID- 2198695 TI - [The epidemiology and primary prevention of cancer of the large intestine]. PMID- 2198696 TI - [The mechanism of the therapeutic effect of norethisterone in hyperplastic diseases of the endo- and myometrium in women of reproductive age]. AB - The paper is concerned with results of a study of clinico-biologic effect of a gestagen norsteroid drug--norcolut--on solitary and combined lesions of the endo- and myometrium. Four hundred and thirty-four patients of reproductive age with hyperplasia or polyps of the endometrium, uterine myoma, internal endometriosis or a combination of the pathologies were examined prior to administration of norcolut and during posttreatment cycle to evaluate the influence of the drug on the female reproductive system. Norcolut exerted the regulatory effect on the rhythm and pattern of menstruation and inhibited tumor growth. Also, changes in localization of myoma nodes, normalization of steroid hormone profile, decrease in the level of estradiol and progesterone receptors, and secretory transformation of the endometrium were observed. Those changes resulted in regression of endometrial lesions. PMID- 2198697 TI - [Immunologic prognosis in hemoblastoses in children]. AB - The diagnostic value of monoclonal antibodies is discussed. The expression of ICO GM1 and ICO-G2 myeloid antigens in pediatric patients with nonlymphoblastic leukemia was associated with poor prognosis whereas patients with the expression of T-cell markers fared better. The prognostic value of the antigens was not altered by brief cytotoxic treatment. The prognosis for non-T-cell ICO-II+ type childhood lymphosarcoma was worse as compared to Ia+ICO-II- lymphoma subset. It was concluded that the biology of malignant cells and degree of cell differentiation (as assessed immunologically) affects treatment outcome significantly and should be considered in individualizing therapy for childhood lymphosarcoma and leukemia. PMID- 2198698 TI - [The results of a clinical study of the preparation hydrazine sulfate]. AB - The paper discusses results of a cooperative study of effectiveness of hydrazine sulfate therapy in 740 patients with primary advanced, recurrent and metastatic solid tumors and malignant lymphomas who had failed all other treatment modalities. Both objective response and symptomatic effect were assessed. Objective response was observed in neuroblastoma, recurrent desmoid, Hodgkin's disease, lung cancer, fibrosarcoma and other tumors. Since hydrazine sulfate provided relief of a wide spectrum of cancer symptoms, it may be recommended for patients with end-stage cancer. PMID- 2198699 TI - [In memoriam Nikolai Petrovich Mazurenko]. PMID- 2198700 TI - [Enzymatic protein hydrolysates for the nutrition of children suffering from a food allergy]. PMID- 2198701 TI - [A reexamination of the norms for the thiamine requirement]. PMID- 2198702 TI - [New possibilities for glucocorticoid therapy of diseases in internal medicine]. PMID- 2198703 TI - [Extracorporeal shockwave lithotripsy of gallbladder calculi]. PMID- 2198704 TI - [Shift work and cardiovascular risk factors]. PMID- 2198705 TI - [Thrombophlebitis--rational diagnosis using real time sonography]. PMID- 2198706 TI - [Availability and proper use of common sunscreening agents]. PMID- 2198707 TI - [Tattooing--a summary of an ancient ritual]. PMID- 2198708 TI - [Preventive vaccinations in HIV infected patients]. PMID- 2198709 TI - [Friedrich Loeffler (1852-1915)--his contributions to bacteriology and virology. In memory of the 75th anniversary of his death]. PMID- 2198710 TI - [The average radiation exposure of the population in middle Europe and its genetic-biologic effect. 1: The different radiation qualities: sources and measured dosage]. PMID- 2198711 TI - [The average radiation exposure of the population of middle Europe and its genetic-biologic effect. 2: The effect of various radiation qualities on the organism]. PMID- 2198712 TI - [Long-term ECG recording--principles, methods, clinical significance]. PMID- 2198713 TI - [Thrombolytic therapy in acute myocardial infarct. 1. Markers for evaluating effectiveness and thrombolytic substances]. AB - By means of serial investigations of coronary angiographies and acute dissections in the acute myocardial infarction (AMI) in the vast majority of the patients fresh thrombi could be made evident as cause of the vascular occlusion. By lysins produced within the body parts of the thrombi can be lyzed (spontaneous lysis up to 20%). However, thrombolytically effective substances considerably increase the recanalization in the first hours after the beginning of the symptomatology. These substances with clinical significance are as follows: streptokinase (SK), urokinase, tissue plasminogen activator (TPA) and acylated streptokinase (APSAC). The broad application of the thrombolytic therapy (TT) is possible only by the intravenous, highly dosed short-term method and demands non-invasive parameters for the judgment of effectiveness [(ECG, ejection fraction globally (EFg), marker protein monitoring)]. Though the ECG allows only conditionedly quantitative statements concerning the size of the myocardial infarction, an estimation of the successful TT in sufficient early recanalization is possible by a dynamics of criterias of ECG and electrocardiographic signs are less distinctly expressed, respectively. The limitation of the size of the myocardial infarction by the successful reperfusion which finds its expression in the remaining left ventricular function is the decisive link for the influence on the quality of the life and the prognosis of these patients. A dynamics of the ejection fraction globally in the effective thrombolytic therapy is to be expressed. For this purpose at least two single measurements (acute phase, control 1st and 2nd week) are necessary. A non-invasive monitoring of marker proteins (enzymes/isoenzymes: CK, CK-MB, LDH and myoglobin, respectively) is suitable for the recognition of the effective thrombolytic therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198714 TI - [Christian Andreas Cothenius (1708-1789). A pro-memoria on the occasion of the 200th anniversary of his death]. AB - The 200th anniversary of the death of Christian Andreas Cothenius gave occasion to appreciate life and work of this personage of a physician. Cothenius maintained manifold connections to Halle, of which the golden doctorate and the heritage of the pharmaceutic enterprises of his teacher Friedrich Hoffmann were treated in this place. The picture of the local relations was supplemented by the history of the Cothenius medal which is today awarded by the Leopoldina of Halle. PMID- 2198715 TI - [Some recent discoveries of metabolism and function of ascorbic acid]. AB - Some newer knowledge concerning the metabolism of the ascorbic acid as well as its importance for the pituitary gland, the adrenal glands, the immune system and the bone formation are described. A large enrichment of the ascorbic acid is present in the pituitary gland and in the adrenal glands. In the pituitary gland the compound is constituent of the Cu-containing peptidyl-glycine-alpha amidizating-monooxygenase which among others is necessary for the formation of alpha-MSH a lack of ascorbic acid diminishes the formation of alpha-MSH at stress the increased binding of ACTH to the cells of the middle and inner layer of the adrenal cortex leads to the fact that about 40 to 60% of the quantity of ascorbic acid are delivered. This evokes an increase of the activity of the adenylate cyclase as well as of the C21-hydroxylase: The synthesis and secretion of glucocorticosteroids increases. When there is a deficiency of ascorbic acid the content of cortisol in the plasma increases. The ascorbic acid is a constituent of the dopamine-beta-hydroxylase. PMID- 2198716 TI - [Pathogenicity of glomerular hyperfiltration, a question of glomerular tolerance?]. AB - As an introduction the concept of the hyperfiltration nephropathy is described. Since it was essentially derived from animal-experimental observations on the rat, the question after the importance for human medicine arises. To this is now argued that a comparable nephronal hyperfiltration possesses a species-different pathogenicity, since the glomerular tolerance to among others the mesangial protein load is also species-different. From this the diagnostic demand for the determination of the glomerular filtration reserve for the recognition of the glomerular hyperfiltration and for the investigation of the microalbuminuria for recognizing the glomerular tolerance. PMID- 2198717 TI - [Johann Georg Lesser (1707-1778) and his contribution to military medicine in the 18th century]. AB - The physician in ordinary and army-surgeon Johann Georg Lesser occupies a considerable position among the physicians about Frederick the Great. In 1735 Lesser was awarded the degree of Doctor of Medicine with a thesis in the field of military medicine. He deserved well of a contemporary organization of military hospitals. Later on he held several offices in the field of medical organization and worked as town physician of Berlin. PMID- 2198718 TI - [The origin of internal medicine roentgen diagnosis in Leipzig. A contribution to the 575 year anniversary of the Leipzig medical faculty]. AB - The detection of the X-rays by Wilhelm Conrad Rontgen in 1895 within shortest time acquired numerous subjects of application in various specialties of medicine. It is tried to describe this development on the basis of internal radiology at the Leipzig Faculty of Medicine. PMID- 2198719 TI - [Pre-, intra- and postoperative echocardiography in cardiovascular diseases. Diseases of the aortic valve]. AB - Nowadays, by means of the conventional and Doppler echocardiography it is possible to diagnose with high sensitivity and specificity a defect of the aortic valve. Apart from references to the etiology kind and size of the lesion of the aortic valve, the degree of an obstruction and/or regurgitation as well as degree of hypertrophy and function of the left ventricle are reliably recognizable. Thereby the one- and two-dimensional echocardiography on the one hand and the Doppler methods on the other a different value is ascribed to in the diagnostic statement. By means of Doppler echocardiography the essential functional parameters of a stenosis of the aortic stenosis such as pressure gradient and surface of the opening of the aortic valve are to be determined noninvasively. An insufficiency of the aortic valve only by Doppler methods can be determined non invasively without doubt. Under certain prerequisites the complex echocardiography can be made dispensable the invasive diagnostics in patients with defects of the aortic valve under preoperative aspects--apart from a coronary angiography. PMID- 2198720 TI - [Transesophageal echocardiography in pre- and postoperative diagnosis of heart diseases]. AB - Transesophageal echocardiography (TEE) represents a substantial methodological extension of the transthoracic approach (TTE). Limitations of TTE can be overcome, furthermore cardiac regions - for instance atrial appendages - can be scanned, which are only difficult to valuate by TTE. The introduction of the endoscope succeed in above 95% of the patients without problems. The transducers work with 30, 48 or 60 single elements and frequencies of 3.5 to 7.5 MHz. The clinical indications for this procedure have included severe cardiac pathology, insufficient TTE, thoracic aortic dissection, prosthetic cardiac valve dysfunction, detection of intracardiac and paracardiac masses, structure lesions and complications of endocarditis, intraoperative monitoring and assessment of critical ill patients in an intensive-care unit. Attending to the prerequisitis and contraindications TEE growth up to an important method for cardiac surgery with regard to prae-, intra- and postoperative diagnostic and evaluation of treatment effectiveness. PMID- 2198721 TI - [Echocardiographic evaluation of mechanical and biological heart valve prostheses]. AB - The complex echocardiography is the method of choice for the non-invasive assessment of patients with prostheses of the cardiac valve. The particular advantages of the method lie in the non-invasiveness, the common ability of repetition, the complete risklessness, the lacking radiation exposure and, what is particularly of importance for the early postoperative phase, the bedside applicability also on the intensive care unit. With regard to potential complications (thrombo-embolism, prosthetic endocarditis) the echocardiography is superior to the invasive examination methods with suspicion to malfunction or leak. The most important prerequisite for an exact interpretation of the findings is the possibility of the comparison with the basis documentation. Moreover, the judgement of prostheses of the cardiac valve demands particular echocardiographic experience, as it in general can be acquired only in a centre. Disturbing echos by valve ring and valve body must be regarded as disadvantage. Disturbances of the cardiac rhythm may simulate defective functions particularly in replacement of the mitral valve with mechanical prostheses. PMID- 2198722 TI - [Hypertrophic obstructive cardiomyopathy]. AB - Today, with the help of modern echocardiographic techniques we are able not only to describe the characteristic changes when a HOCM is present and to determine the intracavitary pressure gradient, but also recognize the functional irregularities typical for the HOCM. Thus, the methodical progress of the echocardiography has essentially enlarged our knowledge about the pathophysiology of this clinical picture. Today, the echocardiography is the method of choice for the diagnostics of the HOCM and for the judgment of the functional consequences of therapeutic interventions. PMID- 2198723 TI - [Measuring subcutaneous fatty tissue as a sonographic parameter for detection of fetal growth retardation and fetal hypertrophy in pregnancy]. AB - This investigation contains a statistical evaluation of sonographic results concerning fetal subcutaneous adipose tissue aiming to examine and assess the relevance of this new sonographic parameter for the detection of fetal growth retardation, resp. fetal hypertrophy during pregnancy. The diagrammatic presentation of the growth of the subcutaneous adipose tissue of eutrophic fetuses shows low validity for the differentiation of hyper- and hypotrophic fetuses. To enable the differentiation between "asymmetric" and "symmetric" types of retardation, the different degrees of growth of the subcutaneous adipose tissue of hypertrophic fetuses have to be taken into consideration. The relation between birthweight and growth of the subcutaneous adipose tissue shows no distinct differentiation of the birthweight, however, presents overlapping categories of the birthweight for diagnostic orientation. PMID- 2198724 TI - [Chorioamniotic dissociation and C-reactive protein as predictors of early premature amniotic rupture]. AB - In 30 cases of cervical incompetence in pregnancy morphological and infectious factors of the amnial membranes were examined with regard to a predictive function versus premature rupture of membranes (PROM). The sonographically visible chorioamniotic dissociation (CAD, cut-off-value greater than or equal to 3 mm) and the C-reactive protein (CRP, cut-off-value greater than or equal to 6 mg/l) showed an sufficient predictive force. The combination of CAD and CRP could predict all cases of PROM. In addition, it could be shown that ascending infections are not only cause of PROM but also of morphological changes of the cervix and the amnial membranes in cervical incompetence. So therapy of an incompetent cervix should include competent vaginal sanitation. An immunological model of premature cervical ripening and damage of the membranes by proteases, kinins and prostaglandins started by phagocytosis activity is discussed. PMID- 2198725 TI - [Control of postoperative vaginal sonographic findings following Shirodkar cerclage]. AB - Up to now postoperative control of the uterine cervix following cerclage was performed by bimanual palpation. Since clinical use of transvaginal sonography it is possible to get objective results about preoperative morphology of the cervix (exact cervical length, dilatation of the cervical canal and opening of internal and external os). Besides postoperative vaginal sonography following cerclage can ascertain lengthening and stabilization of the incompetent cervix and localize the ligature's position. 75 pregnant women between 15th and 30th week of gestation were examined using a 5-MHz vaginal sector scanner probe following Shirodkar cerclage to gain information about the residual cervical length and the distance from the surface of the ectocervix to the ligature's position within the anterior and posterior lip of the cervix. The mean postoperative cervical length was 3.75 cm (1.5 cm-6.5 cm). Compared to the preoperative average length of 3.0 cm (0.5 cm-5.0 cm) the cerclage resulted in an increase of about 25%. The average distance from the surface of the ectocervix to the ligature at anterior lip of the cervix was 1.85 cm, ranging from 0.9 cm to 2.6 cm. The mean value at the posterior lip was 1.56 cm, ranging from 0.8 cm to 2.0 cm. This study showed that the actual positions of ligatures after cerclage operations varied very much. Unsatisfying position can be an explanation why some preterm deliveries can not be prevented. Therefore it is recommended to control the position of the cerclage ligation postoperatively using transvaginal sonography. PMID- 2198726 TI - Ovarian cysts in the fetus and neonate. AB - Three cases of antenatally detected cystic ovarian tumor are reported. Differential diagnostic aspects and management are discussed. PMID- 2198728 TI - [Change in therapy as a model for interaction problems between dermatologists, nurses and patients]. AB - We studied both the frequency of changes in the therapeutic management regarding in-patients with skin diseases and the estimation of these changes by dermatologists, nurses, and the patients concerned. Changing the procedures of topical treatment have been found a special source of conflict between doctors, nurses, and patients. PMID- 2198727 TI - [Detection of fetal growth retardation by instrumental and biochemical monitoring methods]. AB - In 311 high-risk pregnancies between 28 and 42 weeks of gestation a fetal weight estimation by ultrasound, a Doppler sonography of the umbilical artery, an analysis of estriol and HPL-levels in maternal serum and a CTG nonstress-test were performed approximately at the same time. The aim of the study was to compare the value of these methods in the diagnosis of fetal growth retardation. By variation of cut-off levels between normal and pathological range, ROC curves were created which allowed an objective comparison of methods at any cut-off level from ranges of high sensitivity to ranges of high specificity. The course of these ROC curves determine the following rank of test validity: 1. ultrasound measurement, 2. Doppler sonography, 3. HPL assay, 4. CTG nonstress-test, 5. estriol assay. PMID- 2198729 TI - [Current developments in dermatologic virology]. AB - We give a survey of the latest developments in dermatovirology. The actual epidemiologic situation is described with special reference to the increasing incidences of AIDS, condylomata acuminata, mollusca contagiosa, and herpes simplex type 2. The dermatovirological progress achieved during the last few years is mostly due to improved diagnostic techniques, including electron microscopy, and to the introduction of specific virostatic agents. PMID- 2198730 TI - [30 years cardiac pacemaker therapy: a status evaluation]. AB - Antibradycardiac pacemaker therapy has become established as one of the most effective forms of cardiological therapy for the indications AV-block, sick sinus syndrome, bradyarrhythmia, and hypersensitive carotid sinus. About 220,000 systems are implanted per year worldwide, about 32,000 in West Germany. Of the pacing modes, the fixed-rate ventricular single chamber systems (VVI) dominate with a share of almost 90%. Prognostic importance: For AV-block, the improvement of the prognosis by pacemaker therapy is unquestionable, since it increases the cumulative survival rates to 81% and 95% after 1 year and 50% to 65% after 5 years. For sick sinus syndrome, VVI-pacing proves to be a symptomatic measure, no prognostic importance can be proven. It is not conclusively clarified at present whether physiological pacing modes (AAI, DDD) have any such importance. Pacemaker therapy also has no prognostic importance for bradyarrhythmia. Hemodynamic importance: Numerous hemodynamic studies show that fixed-rate VVI-pacing fails to produce a long-term hemodynamic improvement for either an AV-block or a sick sinus syndrome. In sick sinus syndrome hemodynamic improvement can only be achieved by physiological pacing modes (AAI, DVI, DDD), whereby the increase in cardiac output is between 11% to 30%. For AV-block a long-term hemodynamic improvement can only be obtained by atrial triggered pacing modes (VAT, VDD, DDD); this is higher than the values of fixed-rate VVI-pacing by 7-25% at rest, or 10-40% under exercise. Similar results with improvements of the exercise hemodynamics between 22% and 66% are reported for rate-modulated single-chamber pacing (VVIR) for AV-block. Future trends: In the fourth decade of pacemaker therapy, developments point toward the "smart pacemaker", toward rate-modulated systems with combinations of parameters, toward rate-modulated dual-chamber systems and universal antibradycardiac and antitachycardiac systems. PMID- 2198731 TI - [Comparison of enalapril and captopril in the treatment of chronic heart failure]. AB - The long-term effect of enalapril (group 1) and captopril (group 2) on clinical symptomatology and left ventricular function was evaluated in 29 patients with severe congestive heart failure (13 ischemic and 12 dilated cardiomyopathy, four valvular heart disease). During the 6-month observation period, five patients died (two on enalapril and three on captopril therapy = 6-month mortality rate 18%). Nine patients showed no beneficial effect of enalapril or captopril on clinical and hemodynamic findings (= nonresponders). The initial findings on these nine patients were, however, not significantly different from the clinical and hemodynamic findings on the patients who improved. Enalapril had to be discontinued in two patients because of side effects (progressive renal failure and gastrointestinal symptoms, respectively). A total of 22 patients completed the study, 11 treated with enalapril (mean dosage 25 +/- 10 mg/day) and 11 treated with captopril (mean dosage 77 +/- 26 mg/day). After 6 months there was a significant improvement according to the New York Heart Association (NYHA) classification, from 2.4 to 1.9 in group 1 (p less than 0.01) and from 2.7 to 1.9 in group 2 (p less than 0.001). The cardio-thoracic ratio (chest x-ray) decreased significantly from 0.59 to 0.56 (p less than 0.001) in group 1 and from 0.56 to 0.53 (p less than 0.001) in group 2. Physical working capacity (bicycle ergometry) showed a significant increase in both groups from 61% to 81% in group 1 (p less than 0.01) and from 66% to 83% in group 2 (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198732 TI - [The possible reasons for the similarity of the immune and nervous systems]. PMID- 2198733 TI - [The molecular and cellular mechanisms of the bile-secreting function of the liver]. PMID- 2198735 TI - [Neural regulation of the absorptive activity of the gastrointestinal tract]. PMID- 2198734 TI - [The central control of vestibular system reactions]. PMID- 2198736 TI - [Current concepts of the heart conduction system in birds]. PMID- 2198737 TI - [Hormones and neuropeptides--in integrative processes]. PMID- 2198738 TI - [Music for rheumatism--a historical overview]. AB - The history of the use of music to lessen the pain of rheumatism is seen in the use of musical therapy in medicine as a whole. Sources citing the use of music specifically in rheumatism are rare; often, rather than rheumatism, terms like "gout (podagra)" or "joint-pain" are mentioned. This is connected with the obscure and pathognomic perceptions of rheumatism. In the archeo-medicine and for primitive cultures the considered potency of music was primarily dominated by animistic thinking. In antiquity humoral pathology developed a philosophy that tried to explain the benefits of music, even for rheumatism, but found little acceptance. In the Middle Ages and in the Baroque period iatromechanistic conceptions determined music as useful in fight against pain. In the Romantic period there was speculation about music as a causal therapy, but it was shortlived. In the 20th century music is applied as an active therapy in the care of persons suffering from rheumatism; its empiric success as a remedy in rehabilitative and palliative therapy is recognized. PMID- 2198739 TI - [The significance of extra-articular manifestations for the differential diagnosis of musculoskeletal diseases in children]. AB - Musculoskeletal complaints comprise about 7% of all pediatric office visits. The differential diagnosis of these complaints is very extensive. A great diagnostic aid offer quality, distribution and temporal course of the pain of joints, bone and muscles, of an objectively detectable arthritis, and especially of the numerous manifestations of other organ systems: Constitutional signs, fever, skin, mucous membranes, eyes, nervous system, heart, vasculature, lungs, digestive system and urogenital system. Combinations of these often early manifestations are crucial to determine the disease category, which is urgent for further diagnostic measures and for therapy: Bacterial, rheumatic, collagen vascular, traumatic, orthopedic, and neoplastic disease. They are as important for making the final diagnosis and for the early recognition of later manifestations and complications. To achieve an optimal diagnostic efficiency, laboratory investigations should be carefully selected according to the clinical findings and diagnoses. A few regular investigations are valuable for the assessment of disease activity and therapy, and others for the early detection of initially asymptomatic manifestations. PMID- 2198740 TI - [Ultrasound findings in chondrocalcinosis]. AB - The diagnosis of chondrocalcinosis is based on typical radiographic findings and synoviaanalysis. We examined 10 patients with chondrocalcinosis to see whether pathognomonic findings of the disease could also be seen by ultrasound. Ultrasound and x-ray findings were compared. Calcifications of the knee menisci were seen by ultrasound in all patients (10/10). Moreover, in three of six patients calcified carpal disci were observed by ultrasound. Joint mouse, exostosis and calcinosis of the capsula could be demonstrated by ultrasound in all instances. In one case the joint mouse was only seen by ultrasound; tomography finally confirmed this diagnosis. Though ultrasound findings in chondrocalcinosis cannot be considered pathognomonic, typical changes of the diseases can be found by this technique. Since ultrasound is a method of increasing interest in rheumatic diseases, those findings may initiate the consideration of the diagnosis. PMID- 2198741 TI - [Septic arthritis as an initial manifestation of endocarditis]. AB - A 60-year-old female patient was admitted to the hospital with high fever and an acute onset of pauciarticular arthritis. Clinical examination and ultrasound imaging of the right knee demonstrated a severe synovitis with a large synovial effusion and a Baker's cyst. Arthrocentesis showed an opaque viscous synovial fluid with a highly elevated white blood cell count. In synovial fluid cultures and in serial blood cultures Aerococcus viridans (Av) was detected. Further examination revealed a mitral valve endocarditis as the origin of the septicemia. This case report is the first one to describe the association of an endocarditis and a septic arthritis due to Av. PMID- 2198742 TI - [Johannes Volkmann (1889-1982)--his contribution to the development of excretory urography. Medical historical considerations on the occasion of his 100th birthday]. AB - On the occasion of his 100th birthday the curriculum vitae and the scientific work of the surgeon Johannes Volkmann (1889-1982) are presented. The influence of his teacher Friedrich Voelcker (1872-1955) and the importance of Volkmann to the development of intravenous urography are emphasized. PMID- 2198743 TI - [Fetal respiratory movements and their regulation]. AB - In 1972, fetal breathing movements were clinically rediscovered. Details of their episodic occurrence, frequency, inspired volume, pleural pressure, and the nearly absolute independence of fetal blood gases were investigated in animal experiments. In the human being, there is also an association between fetal breathing and sleep state: fetal breathing movements were confined almost exclusively to periods of REM sleep. The pattern of respiratory frequency changes as gestation progresses; the rates decrease as term approaches. Hardly any breathing movement can be detected during labor. The fetal respiratory centre is capable of rhythmic movements, but there is a lack of response to basic chemical stimuli from the periphery of the body. The association between fetal breathing and REM sleep implies that the connection between breathing and behaviour is already established before birth; but in the fetus, the link between breathing and metabolism is not yet forged. Throughout postnatal life this linkage predominantly regulates breathing. The difference between fetus and newborn in the reaction to chemical stimuli implies a change at birth related to the glomera cells of the carotid bodies. Under the influence of the marked increase in the sympathetic tone there is a major increase in the sensitivity of the receptor cells to oxygen deficiency immediately after birth. PMID- 2198744 TI - [Response to the contribution, "Chlamydia infections", by U. B. Hoyme]. PMID- 2198745 TI - Low dose metformin in the treatment of type II non-insulin-dependent diabetes: clinical and metabolic evaluations. AB - Low doses of metformin (500 mg twice daily) were administered to 20 diabetic patients, combined with the original sulfonylurea treatment which had become ineffective even at full dosage. After 1 and 5 weeks, the effects of the drug on glycemic control, blood intermediate metabolites and monocyte insulin receptors were monitored. Metformin clearly improved glycemic control by reducing both fasting blood glucose from 189.88 +/- 21.11 mg/dl to 131.12 +/- 16.02 mg/dl after 1 week and to 130.11 +/- 13.29 mg/dl after 5 weeks (p less than 0.025 both after 1 and 5 weeks); the diurnal blood glucose average fell from 235.33 +/- 24.11 mg/dl to 174.66 +/- 23.45 mg/dl (p less than 0.0025) after 1 week and to 177.65 +/- 21.71 mg/dl (p less than 0.0005) after 5 weeks. Consequently both blood glycosylated hemoglobin (p = n.s. after 1 week, p less than 0.025 after 5 weeks) and serum fructosamine (p less than 0.0025 after both 1 and 5 weeks) also decreased after metformin treatment. No change in plasma insulin and C-peptide levels was reported and no modification in diurnal rhythms of blood lactate, pyruvate, alanine glycerol and beta-OH-butyrate was detected at any time during metformin treatment. All the changes documented in the binding values were already complete at the end of the first week; insulin binding to monocytes increased slightly but significantly (p less than 0.05) and the number of receptors per cell rose (p less than 0.05) but could not be correlated to any index of glycemic control. These data suggest that the antidiabetic action of metformin is neither related to its lactate-increasing activity nor does it depend upon its inducing an increase in insulin binding values. This metformin related hypoglycemic effect might be the result, at least in part, of a reduced oxidative phosphorylation without inhibition of hepatic gluconeogenesis and/or of decreased hepatic glucose output. Moreover, our data are also consistent with the hypothesis that metformin might affect insulin action at a post-receptor level. PMID- 2198746 TI - Comparison of BT-PABA test and fecal chymotrypsin measurements in normal subjects and diabetic patients. AB - A N-benzoil-L-tyrosil-PABA test on 6h urine collection, a plasma PABA assay 2 h after administration and a fecal chymotrypsin assay were performed on 66 patients (36 controls and 30 type 2 diabetic patients on insulin therapy). All patients were hospitalized and without gastrointestinal and renal disease. The mean values of plasmatic PABA and fecal chymotrypsin were significantly lower in the diabetic group than in the controls (p less than 0.025 and p less than 0.01, respectively), although they remained within normal range. But this was not the case for PABA urinary excretion values. This may indicate a slower but more protracted PABA absorption during the third or fourth hour with the result that urinary excretion over 6h is not greatly affected. There was good correlation between fecal chymotrypsin values and both PABA urinary excretion values and serum PABA values, a trend observed both in diabetics (p less than 0.005 and p less than 0.001, respectively) and in controls (p less than 0.001 and p less than 0.005, respectively). This could indicate that even at lower mean levels, the diabetic patients show the same behavior pattern and therefore maintain the same indexes of correlation as the control population. Our results suggest that these indirect, but simple, economical and well-tolerated tests could be considered a valid alternative for investigating pancreatic function especially in those patients that cannot be tested by a Secretin-Cerulein test. PMID- 2198747 TI - Pancreatic polypeptide secretion after insulin infusion and protein meal in juvenile type 1 diabetic subjects. AB - An impaired pancreatic polypeptide response (PP) after hypoglycemia has been described in type I diabetic patients with overt autonomic neuropathy. Some authors have suggested that PP release might be useful as sensitive indicator of autonomic neuropathy. The meal test is safer and simpler than the insulin infusion test as PP stimulus. The aim of this study was to compare PP response to insulin infusion and protein meal test and to correlate these responses to the presence of measurable neuropathic disturbances. We thus studied 13 IDDM children and adolescents and 6 normal children. In diabetics the PP response to both tests was not different from that of the control subjects, but PP response to insulin infusion was inversely correlated to the duration of illness and was significantly lower in subjects with pathological heart rate response when compared to the control group. PP responses to the two stimuli were not correlated. We suggest that reduced PP response to hypoglycemia is an early sign of autonomic neuropathy as well as impairment of beat-to-beat variation when impaired PP response to meal test is still not evident. PMID- 2198748 TI - The role of hypertension in the development of nephropathy in type 1 (insulin dependent) diabetes mellitus. AB - Which comes first when developing clinical diabetic nephropathy, the blood pressure rise or the increasing urinary albumin excretion? This issue is discussed based on recent literature of studies in humans with Type 1 (insulin dependent) diabetes mellitus. We conclude that hypertension has a central role in the progression of diabetic nephropathy and has deleterious effects on the life expectancy of patients who already have signs of diabetic renal disease in terms of elevated urinary albumin excretion. However, blood pressure is preceded by small increments of urinary albumin excretion rates, an indicator of universally increased vascular leakiness, and thus does not seem to be the cause of diabetic nephropathy. PMID- 2198749 TI - Ivermectin--clinical trials and treatment schedules in onchocerciasis. AB - Initial clinical trials with ivermectin were performed in patients with both roundworm infestation and onchocerciasis. Obvious clinical safety allowed for rapid progression through 5-30-50-100-150-200 mcg/kg in infected patients. Initial studies showed some effect at 50 mcg/kg; subsequent double-blind controlled studies, either with placebo or diethylcarbamazine (DEC), confirmed the efficacy of ivermectin as well as further defining its safety profile. Absence of adverse eye findings or serious systemic reactions justified the further open trials. Studies of patients treated at 6, 12, or 18 month intervals showed a long lasting effect of ivermectin in reducing skin microfilaria counts. Phase III studies confirmed safety and efficacy and further refined the dose to 150 mcg/kg every 12 months. Large trials in Liberia and other countries in West Africa, and subsequently under Onchocerciasis Control Program (OCP), included approximately 120,000 persons carefully followed during which few patients with serious adverse experiences were reported. These extensive field trials confirmed the relative safety allowing for broad distribution of ivermectin in programs not able to provide physician monitoring. PMID- 2198750 TI - Large scale ivermectin distribution and its epidemiological consequences. AB - Community trials were started to address questions concerning the safety of ivermectin during large scale treatment, its potential for transmission control, its effect in preventing ocular onchocercal disease, its acceptability and the organization of large scale treatment. A summary is presented of the major, latest results on the short-term epidemiological impact of large scale ivermectin treatment, as observed in eight community trials undertaken in the Onchocerciasis Control Programme in West Africa (OCP). Ivermectin treatment resulted in a 96% 99% reduction in the mean load of microfilariae (mf) in the skin in treated patients. The subsequent mf-repopulation of the skin was faster than in the clinical trials and after 12 months the mean loads had returned to more than 40% of the pre-treatment load. Ocular mf loads were also greatly reduced and a post treatment regression of early lesions of the anterior segment of the eye was observed. The transmission of Onchocerca volvulus was reduced by some 60% during the first year after treatment in one trial but no additional reduction was observed after the second treatment round. These results, and other recent research findings, have been used to quantify an epidemiological model for the transmission and control of onchocerciasis. Preliminary results of computer simulations of the predicted long-term epidemiological impact of large scale ivermectin treatment indicate that ivermectin treatment may play a very important role in disease control but that it is unlikely to become a practical tool for transmission control in endemic foci. Ivermectin treatment appears to be the most appropriate method for control of recrudescence of infection in an area where the parasite reservoir has been virtually eliminated by vector control, such as in the core area of the OCP. PMID- 2198751 TI - Ivermectin treatment of ocular onchocerciasis. AB - Ivermectin, a recently developed macrocyclic lactone with broad antiparasitic activity, has been shown by a series of clinical trials to be safe and effective in the treatment of human infection with Onchocerca volvulus. Although it is rapidly microfilaricidal, it does not cause a severe reaction as is seen with diethylcarbamazine treatment. In patients with onchocerciasis, a single oral dose of ivermectin (150 micrograms/Kg) repeated once a year leads to a marked reduction in skin microfilaria counts and ocular involvement, although ivermectin has no known long-lasting effects on the adult worms. With treatment there is no significant exacerbation of either anterior or posterior segment eye disease even in those with severe ocular disease. Treatment leads to a marked and prolonged improvement in ocular status. Because of its safety and efficacy, ivermectin can be used on a mass scale and promises to revolutionize the treatment of onchocerciasis. PMID- 2198752 TI - Veterinary use of ivermectin. AB - Following the development of a unique claim structure encompassing both nematode and arthropod species, ivermectin was first introduced as a veterinary parasiticide in 1981. For cattle(c), sheep(s), horses(h) and pigs(p) injectable(c,s,p), oral(c,s,h) and topical(c) products are available delivering ivermectin at 200 to 500 micrograms/kg. Efficacy extends to nematodes of the gastrointestinal and respiratory tracts, conjunctival sac and soft tissues. Among the arthropod parasites claims have been established for the biting fly Haematobia irritans(c), the screw-worm Chrysomyia bezziana(c), larvae of the oestrid flies Hypoderma spp.(c), Dermatobia hominis(c), Oestrus ovis(s) and Gastrophilus spp.(h), lice(c,p), mange mites(c,s,p) and the ticks Boophilus spp.(c) and Ornithodorus savignyi(c). In the dog two oral formulations are available for the prevention of heartworm disease caused by Dirofilaria immitis by administration of 6 micrograms/kg once monthly during the mosquito season. PMID- 2198753 TI - Abamectin as a pesticide for agricultural use. AB - The avermectins are a family of macrocyclic lactones, produced by the soil organism Streptomyces avermitilis, which were discovered in the mid-1970's as a direct result of a screening effort for natural products with anthelmintic properties. Avermectin B1 (abamectin), the major component of the fermentation, also showed potent activity against arthropods in preliminary laboratory evaluations and was subsequently selected for development to control phytophagous mites and insect pests on a variety of agricultural and horticultural crops worldwide. Major applications for which abamectin is currently registered include uses on ornamental plants, citrus, cotton, pears and vegetable crops at rates in the range of 5 to 27 grams abamectin per hectare as a foliar spray. Abamectin has shown low toxicity to non-target beneficial arthropods which has accelerated its acceptance into Integrated Pest Management (IPM) programs. Extensive studies have been conducted to support the safety of agricultural uses of abamectin to man and the environment. Abamectin is highly unstable to light and has been shown to photodegrade rapidly on plant and soil surfaces and in water following agricultural applications. Abamectin was also found to be degraded readily by soil microorganisms. Abamectin residues in or on crops are very low, typically less than 0.025 ppm, resulting in minimal exposure to man from harvesting or consumption of treated crops. In addition, abamectin does not persist or accumulate in the environment. Its instability as well as its low water solubility and tight binding to soil, limit abamectin's bioavailability in non target organisms and, furthermore, prevent it from leaching into groundwater or entering the aquatic environment. PMID- 2198755 TI - Species complex of vectors and epidemiology. AB - This work collates previous and recent cytotaxonomically defined segregates of the Simulium damnosum complex from western and eastern Africa. Standard cytotaxonomic procedures were used on new samples from Nigeria, Cameroon and Malawi. The main onchocerciasis vectors comprising cytotypes, cytoforms and cytospecies are highlighted and indications of host preferences are given. Thyolo form, the vector implicated in the Thyolo Highlands of Malawi, is reported for the first time. Also reported are new foci of two genetically distinct savanna taxa: Volta form and S. damnosum s.s.. The associations between forest taxa and onchocerciasis in the Forest Zone of west Africa together with the interplay of vector distributions at the interface of this and the Savanna Zone in relation to the epidemiology of onchocerciasis are discussed. The role of individual members of the species complex in epidemiology is less understood in east Africa and the Yemen but is briefly discussed. PMID- 2198754 TI - The effect of ivermectin on the uptake and development of O. volvulus microfilariae in S. damnosum s.l. PMID- 2198756 TI - Molecular/biochemical development of new drugs against macro- and microfilariae. PMID- 2198757 TI - Clinical pharmacokinetics of drugs against onchocerciasis. PMID- 2198758 TI - The Wellcome Foundation/World Health Organisation Onchocerciasis Chemotherapy Project Joint Programme to discover and develop a macrofilaricide for onchocerciasis. AB - The primary objective of the Wellcome Foundation/World Health Organisation Onchocerciasis Chemotherapy Project, which began in July 1982, was the discovery and development of a safe and effective macrofilaricide for the treatment of onchocerciasis in man. A multidisciplinary Team of biologists, biochemists and medicinal chemists was assembled. They investigated a variety of potential targets in filariae and carried out in-depth lead optimisation studies on a number of different chemical series. A valuable contribution was made to our understanding of filarial biology and biochemistry and the susceptibility of filariae to various metabolic inhibitors. However, the ultimate goal of identification of a compound worthy of evaluation in man was not achieved and the programme was closed at the end of June 1989. Factors that contributed to this situation and some overall conclusions are discussed. PMID- 2198759 TI - Factors affecting the differential susceptibility of males and females to onchocerciasis. AB - The evidence for male/female differences in prevalence, density of infection and clinical disease due to onchocerciasis is reviewed and related to what is known about differential exposure of females to infective vectors. Sex differentials are most marked in savanna areas of high transmission, and in these areas, worm burdens are lower from early childhood in females--as are ocular lesions. In forest areas, sex differences are less marked and ocular lesions are similar in men and women. Sex differences are most evident under conditions of high transmission and it is suggested that females are more resistant to infection than males. There is little substantive evidence that onchocerciasis is less frequent in females on the basis of exposure but controlled exposure and immunological studies, analysed by age and sex, are needed to confirm this. Little is known about onchocerciasis in pregnancy but increased resistance could influence the risk of transmission of infection from mother to child in highly endemic areas. Onchocerciasis in pregnancy is also likely to affect immune response to tetanus toxoid vaccination in mothers and birthweight of children. The disease therefore represents an important public health problem for women and their offspring. PMID- 2198760 TI - Review of vector control prior to the OCP. AB - It is a little over 60 years since Blacklock, in an elegant study, demonstrated that in Sierra Leone human onchocerciasis was transmitted by a Simulium fly. Amazingly within 6 years of Blacklock's discovery an attempt was made, mainly using environmental management, to control Simulium in the Chiapas focus of Mexico, though this was not successful. Later Buckley was successful in eradicating Simulium neavei from the small Riana focus in Kenya by clearing riverine forest. However, it was not until DDT became widely available that Simulium control entered its heroic phase with campaigns in Kenya, Uganda and Zaire, some of which were highly successful. This led to an interest in controlling the vector in West Africa. The very different pattern of disease with very large foci virtually contiguous across tens of thousands of square kilometers suggested a difficult proposition and early attempts were not very successful. There is much of interest in the East and Central African schemes and in the West African forerunners of the OCP. In this talk an attempt will be made to capture something of the flavour of these pioneering efforts, to give credit to the men involved, and to highlight the successes against both the S. neavei and S. damnosum complex, and the advances which contributed to the successful planning of the OCP. PMID- 2198761 TI - Human onchocerciasis--an overview of the disease. AB - The general characteristics of Onchocerca volvulus infection and its transmission are outlined in this overview of human onchocerciasis. The pathogenic role of the microfilariae, producing lesions of the skin, lymphatic system, eye and deep organs, are described, along with the main clinical manifestations of the disease. The global prevalence and distribution of onchocerciasis are given. Best estimates in 1985 gave 86 million persons at risk, 17.8 million infected, 336,400 blind and a like number suffering from severe visual impairment. The vast majority was in Africa. The impact of onchocerciasis on communities in the Sudano Guinean savanna zone of Africa is outlined, emphasizing the very high blindness rates and the increased mortality among the blind. Communities so affected cannot remain economically viable. They are forced to desert their villages and the fertile land near rivers. The background to the establishment of the Onchocerciasis Control Programme in West Africa (OCP) is given and the successful 10-year results of this campaign, which is based on prolonged, regular Simulium larviciding, are outlined. In the context of the future of the OCP and of the control of onchocerciasis elsewhere in the world, the need for improved chemotherapy is discussed. The prospects for large-scale suppressive therapy have greatly improved following the registration of ivermectin in 1988 for use in human onchocerciasis. The potential and possible uses of this drug, as a single dose, non-toxic microfilaricide, which excites very little Mazzotti reaction and has a prolonged microfilarial suppressant action, are discussed. It is considered that an effective non-toxic macrofilaricide is still a prime need for onchocerciasis control. PMID- 2198762 TI - Medicare budget physician payment and the CRNA fee schedule. PMID- 2198763 TI - Human immunodeficiency virus and the fetus. AB - About 2 percent of current cases of acquired immunodeficiency syndrome are among patients less than 13 years of age. When a woman infected by the human immunodeficiency virus (HIV) becomes pregnant, her neonate has approximately a 40 percent chance of becoming infected vertically in the perinatal period. Experience in detecting HIV-infected pregnant women and in diagnosing their affected neonates has been less than satisfactory. In this review, the epidemiology, pathogenesis, transmission, clinical manifestations, diagnosis, and treatment-prevention of perinatal HIV infection are discussed. PMID- 2198764 TI - Diagnosis and management of infectious vaginitis. AB - Vaginitis is an important gynecologic disorder that accounts for nearly 5 million office visits to physicians each year. Infectious vaginitis is the most common cause for an abnormal vaginal discharge; other possible causes include cervicitis, atrophic vaginitis, physiologic discharge, physicochemical vaginitis, and psychosomatic vaginitis. Although the history and physical examination may suggest the diagnosis, laboratory confirmation is required. The vaginal pool wet mount remains the cornerstone in the office diagnosis of vaginitis, with the "sniff" test, vaginal pH determination, and the "swab" test all playing important adjunctive roles. Metronidazole is the only effective treatment for trichomoniasis in the United States. The vaginal administration of an imidazole antifungal agent is the mainstay of treatment of vaginal candidiasis. Despite a search for alternative drug regimens, a 7-day course of metronidazole therapy remains the treatment of choice for bacterial vaginosis. PMID- 2198765 TI - [Primary abscess of the psoas]. AB - We present in this paper a series of cases from our Service of primary abscesses in psoas. We consider the appearance of immunosuppressed patients as a relevant factor of its etiopathogenicity. We believe that a C.A.T. is the best diagnostic method. All three patients that underwent open surgery have had complications. The patients treated with percutaneous puncture has shown a favourable evolution. PMID- 2198766 TI - [Secondary tumors of the bladder of metastatic origin; a new case and review of the literature]. AB - We present a fresh case of gastric carcinoma with metastasis at vesical level in the year subsequent to the performance of a Billroth II type gastrectomy for this reason. The vesicle tumour manifested itself in the form of hematuria, irritative miction syndrome and obstruction of the upper left urinary tract. We have reviewed the literature of the last 10 years and confirmed, on the one hand, the infrequency of these tumours and, on the other, that the commonest localization of primary neoplasia is the stomach. PMID- 2198767 TI - [30 years of alkalinizing treatment]. PMID- 2198768 TI - Transient induction of gene expression in the nervous system in response to extracellular signals. PMID- 2198769 TI - A role of ras oncogenes in carcinogenesis and differentiation. PMID- 2198771 TI - Neural cell adhesion molecule as a regulator of cell-cell interactions. PMID- 2198770 TI - Cerebellar granule cell migration involves proteolysis. PMID- 2198772 TI - Structure and function of the neural cell adhesion molecules NCAM and L1. PMID- 2198773 TI - Monosialogangliosides and their action in modulating neuroplastic behaviors of neuronal cells. PMID- 2198774 TI - Serotonin and morphogenesis in the cultured mouse embryo. PMID- 2198776 TI - Early experimental influences on serotonin pathways during brain development. PMID- 2198775 TI - The ontogeny of adrenergic fibers in rat spinal cord. PMID- 2198777 TI - Ontogeny of the glucocorticoid receptor in the rat brain. PMID- 2198778 TI - Molecular genetic approaches in the therapy of Alzheimer's disease. PMID- 2198779 TI - Aberrant protein kinase C cascades in Alzheimer's disease. PMID- 2198780 TI - Cell lineage studies in avian neural crest ontogeny. PMID- 2198781 TI - Characterization of trophic factors stored and secreted by neurons. PMID- 2198782 TI - Basic fibroblast growth factor affects the survival and development of mesencephalic neurons in culture. PMID- 2198783 TI - Relative addiction potential of major centrally-active drugs and drug classes- inhalants and anesthetics. AB - The inhalation of a wide variety of substances for recreational purposes is a health problem of worldwide proportions. The inhalation of non-narcotic agents, such as volatile inhalants (e.g., solvents and glues), anesthetics and nitrites, adds significantly to the growing number of substance abusers. This is of particular concern because it affects the younger members of the population, and the substances abused are, for the most part, legally obtainable. The toxicity of these inhaled substances are reviewed and compared, as are their potentials for addiction and dependence. PMID- 2198784 TI - PCP and hallucinogens. AB - In this review phencyclidine and related arylcyclohexylamines and hallucinogens, using LSD as the prototype, are considered as two distinct classes of abused drugs. Within these classes drugs that are found on the street are discussed, and a current epidemiological summary is provided. The abuse liability and dependence potential of these drugs are evaluated by considering four major determinants of their abuse. First, is the ability of a drug to function as a positive reinforcer and increase the probability of operant behavior leading to its delivery. Animal data describing the reinforcing effects of PCP are reviewed with respect to the influence of variables controlling drug-reinforced behavior; however, there are no animal models of hallucinogen-reinforced behavior. Several methods of quantifying reinforcing efficacy are discussed. A second determinant is the subjective effects of the respective drugs. These effects are described and compared across drugs based on clinical reports in humans and drug discrimination studies in animals. A third determinant is the behavioral and physiological toxicity that results from acute and chronic use of these drugs. Clinical reports and results of sensitive tests that have been developed for laboratory animals are reviewed. A fourth determinant is the dependence potential that exists with these drugs, measured by tolerance development and the extent to which behavioral and physiological disturbances occur when drug use is terminated. PMID- 2198785 TI - The opioids: abuse liability and treatments for dependence. AB - The opioids vary greatly in addictive potential, from the highly addictive such as heroin to the opioid antagonists such as naltrexone, which can be used to treat opioid dependence and overdose. The various opioid compounds have different euphorigenic properties and also produce withdrawal syndromes of distinct patterns of duration and intensity. Dependence liability is affected by both the pleasure-seeking motives for initiating drug use and the painful consequences of abstinence or withdrawal. Detoxification, which takes 7-10 days for the short acting opioids, is usually the first stage in treatment. Methadone is often used as a preliminary stage in detoxification, but some patients are maintained on methadone for years, since it allows them to lead relatively normal lives. Non opioid drugs used to control withdrawal symptoms include clonidine. After detoxification, naltrexone, a long-acting opioid antagonist, can be administered orally to prevent relapse. PMID- 2198786 TI - Abuse liability of barbiturates and other sedative-hypnotics. AB - The principal action of the sedative-hypnotic drugs, of whom the barbiturates are the most widely known and utilized, is to produce drowsiness and promote sleep. At one time these were also the only drugs available to calm seriously anxious or disturbed people. Unfortunately, in addition to their clinical applications these drugs manifest a very high abuse potential. Experienced drug abusers report feelings of well-being and euphoria while under the influence of these drugs. Self-administration experiments conducted in animals have shown that the barbiturates are potent reinforcing agents. In controlled studies in humans, former drug abusers express a preference for barbiturates over benzodiazepines and will "work" to receive barbiturates. Long term consumption of the sedative hypnotics, particularly barbiturates, leads to dependence characterized by a severe, potentially life-threatening abstinence syndrome following the abrupt withdrawal of the drug. Withdrawal manifestations include delirium and grand mal seizures. Because of the high abuse potential of these drugs, their manufacture and distribution has been greatly curtailed, and for most clinical applications they have been largely replaced by drugs, e.g., the benzodiazepines, which appear to have much less abuse liability. PMID- 2198787 TI - An analysis of the addiction liability of nicotine. AB - Even though the percent of adults who smoke has been reduced dramatically in the last 20 years, more than 50 million people continue to use tobacco on a daily basis. A majority of these people claim that they would like to stop smoking, but cannot. This review discusses the data suggesting that tobacco smokers are seeking nicotine. The behavioral effects elicited by nicotine and its relative reinforcing properties, as well as the development of tolerance to nicotine and the role of nicotine in the tobacco withdrawal syndrome are discussed. The data indicate that nicotine has addiction liability, but this liability is probably not equal to that of other agents such as cocaine and the opiates. PMID- 2198788 TI - [The retroperitoneal rhabdomyosarcoma: a case report]. AB - A case of rhabdomyosarcoma in the retroperitoneal space is reported. The patient, a 71-year-old man, visited us with a complaint of left flank pain. The tumor measuring 13 x 10 x 7 cm and weighing 700 g, was removed operatively. The patient had no evidence of recurrence in 12 months following surgery. PMID- 2198789 TI - [Multilocular cystic renal cell carcinoma: a report of 2 cases]. AB - We report 2 cases of renal cell carcinoma which rarely occur as multilocular cystic masses. By means of echography, both cases were discovered as abnormal shadows occupying the middle portion of the left kidney. Using computerized tomography and selected renal arteriography, we tried to obtain an accurate diagnosis, but few specific malignant findings were gained. Finally, we made the histopathological diagnosis. In addition, we concluded by careful pathological examination that they were multilocular cystic growths. It was difficult to differentiate them preoperatively from multilocular cystic nephroma. Both patients are still alive without tumor recurrence. PMID- 2198790 TI - [A case of primary localized amyloidosis of the urinary bladder]. AB - A case of primary localized amyloidosis is reported. The patient was a 73-year old female who suffered from miction pain and consulted our department. There was a 1.5 x 1.5 cm slightly red, nonpapillary tumor around the right ureteral orifice in cystoscopy. The diagnosis was amyloidosis with cystitis hemorrhagica histopathologically. After the treatment with antibiotics for about one month there were no symptoms and no tumors in the urinary bladder cystoscopically. The clinical course was relatively good. The treatment varies from transurethral resection to total cystectomy with urinary diversion. This case was cured by non operative treatment, but close follow-up of the patient is necessary because of the frequency of multiple recurrence. PMID- 2198791 TI - Low-dose total body irradiation in non-Hodgkin lymphoma: short- and long-term toxicity and prognostic factor. AB - The toxicity of low-dose total body irradiation (LTBI), the prognostic factors related to survival and relapse-free survival, and the efficacy of treatment given for relapse after LTBI were analyzed in 68 patients with non-Hodgkin lymphoma (NHL) treated at the Rotterdamsch Radiotherapeutisch Instituut. All patients received LTBI between 1973 and 1979. The patient material was heterogeneous with respect to malignancy grade, stage, age, and therapy given before or after LTBI; the unifying principle was that all patients received LTBI and had symptomatic NHL. Analysis of prognostic variables with Cox's model revealed grade (p less than 0.001) and age (p = 0.004) as predictors for survival and grade (p less than 0.001) and dose of LTBI (p = 0.056) as predictors for relapse-free survival after LTBI. No subjective toxicity was observed during or after LTBI treatment. Hematologic toxicity was dose-limiting and was increased if patients had received cytotoxic treatment before LTBI. LTBI-related hematologic toxicity was lower in patients with low-grade NHL than in those with intermediate or high-grade NHL, was limited in time, and recovered in all patients. Patients relapsing after LTBI received a variety of therapies. Response rates were high, but of short duration, especially in intermediate or high-grade NHL. Duration of response was progressively shorter after multiple relapses. PMID- 2198792 TI - Successful treatment of hair cell leukemia with 2'-deoxycoformycin after failure of interferons alpha or beta. AB - Two patients with hairy cell leukemia (HCL) who failed alpha-2a-interferon and one who failed beta-ser-interferon were treated with 2'-deoxycoformycin (DCF), 4 mg/m2, by intravenous bolus infusion every 2 weeks. All three patients achieved a complete response, continuing for 9+, 14+, and 15+ months. Treatment was discontinued when complete remission was diagnosed. DCF-induced remission has not been previously reported after beta-ser-interferon failure. These patients, as well as 12 others in the literature reviewed herein, demonstrate the efficacy of DCF in HCL patients unresponsive to alpha, beta, and gamma interferon. PMID- 2198794 TI - Echinomycin (NSC 526417) in advanced ovarian cancer. A phase II trial of the Gynecologic Oncology Group. AB - Twenty-two patients with recurrent carcinoma of the ovary progressive after initial chemotherapy (21 with cisplatin-based treatment) were entered on a phase II trial utilizing Echinomycin at a dosage of 1,500 micrograms/m2 every 4 weeks. There were two complete responders and no partial responders (9% response, 95% confidence intervals for complete and partial responses of 1-29%). Major toxicity was modest and consisted mainly of nausea and vomiting. Echinomycin displays minimal activity as salvage therapy in women with advanced ovarian cancer at this dose and schedule. PMID- 2198793 TI - Bone-only versus visceral-only metastatic pattern in breast cancer: analysis of 150 patients. A GOCS study. Grupo Oncologico Cooperativo del Sur. AB - The medical records of 510 patients with metastatic breast cancer were retrospectively reviewed. Seventy-seven patients with metastases confined to skeleton and 73 patients bearing visceral-only disease were identified. All patients had a disease-free interval greater than or equal to 6 months and received systemic therapy with any of the following modalities: chemotherapy, hormonotherapy, or chemohormonotherapy. The clinical features, response to treatment, and survival were analyzed and compared for both groups. Median survival of patients with osseous metastases was 28 months, while it was 13 months for those patients with a visceral pattern (p less than 0.001). Response rates to first and second line systemic therapy for both metastatic patterns showed no significant differences, suggesting a similar degree of sensitivity or resistance in both groups. Objective regression to first therapy was 45% in the group with bony disease and 41% among patients with visceral involvement; median duration of response was 16 months and 13 months, respectively. In both groups progressive disease conserved the original metastatic pattern in most patients. We conclude that although a superiority in survival was evident for the osseous metastatic pattern, for these patients efforts should be made to select the least aggressive therapy in order to avoid excessive toxicity. Further studies are needed to confirm our findings. PMID- 2198796 TI - 3-D radiation therapy treatment planning: overview and assessment. AB - A 3-D treatment planning system is one that can represent all radiation therapy treatment machine motions, and which can calculate the dose at any point in the patient treatment volume. As a corollary to these two requirements, a 3-D planning system must also be able to display 3-D plan geometry and doses in some useful way. This article reviews three visible aspects of 3-D planning systems: graphic displays, dose computation methods, and ease of use. It also discusses a less visible, but no less important, aspect: the underlying software engineering. Although 3-D planning systems first appeared in research institutions more than a decade ago, and potential benefits have been demonstrated, they are used only rarely in routine clinical practice. This review concludes that adequate displays and computation techniques are now available, but improved packaging, engineering, and ease of use are required before 3-D planning will be practiced widely. PMID- 2198795 TI - A phase II trial of carbetimer for the treatment of colorectal cancer. A trial of the Northern California Oncology Group. AB - Carbetimer (carboxyimamidate) was administered at a dose of 6,500 mg/m2/day intravenously for 5 consecutive days to 14 patients with measurable metastatic or recurrent colorectal cancer in a single institution phase II study of the Northern California Oncology Group. A total of 38 cycles of therapy were administered; nine patients completed at least three cycles of treatment. No partial or complete responses were observed. One patient did have a greater than 50% response in the liver while developing new retroperitoneal lymphadenopathy and is considered a nonresponder. Carbetimer was well tolerated with elevations of calcium from 10.2 to 12.5 mg/dl in nine patients, prolongation of prothrombin time and partial thromboplastin time in 14 patients, proteinuria in 10 patients, dizziness in six patients, nausea in two patients, and venous pain during infusion in three patients. Myelosuppression was not observed. Carbetimer at this dose and schedule is inactive in the treatment of colorectal cancer. PMID- 2198798 TI - Interstitial thermoradiotherapy: review on technical and clinical aspects. AB - Interstitial hyperthermia (IHT) combined with brachycurietherapy (thermoradiotherapy) has gained increasing popularity among radiation oncologists due to its potential as an effective radio- and chemosensitizer. IHT offers considerable advantages over percutaneous methods: confined treatment volume, better sparing of normal tissue, accessibility of deeper tumors, more homogeneous therapeutic temperature distribution, and better control and evaluation of thermal parameters using extensive "thermal mapping" procedures. This article addresses technical principles and clinical applications of IHT methods, radiofrequency (RF), microwave (MW), and hot source (HS) hyperthermia. Clinical phase I/II studies have used IHT palliatively for primary advanced, persistent, or local recurrent tumors, which have responded poorly to conventional treatment. The preliminary clinical data on greater than 500 patients treated with interstitial thermoradiotherapy are extremely promising despite the broad variation among the different treatment approaches. The observed complete response (CR) rate in various clinical trials ranges between 11 and 74%. The differences between the various techniques are minor, with a CR of 57% for interstitial RF hyperthermia (169 of 299 patients) and 60% for interstitial MW hyperthermia (130 of 215 patients). Despite extensive pretreatment, the total observed compliation rate of 22% for RF hyperthermia (67 of 299) and 21% for MW hyperthermia (45 of 215) is acceptable. The prognostic treatment factors identified are tumor volume, applied radiation dose, sufficiently high minimum tumor temperatures, and good thermal parameters, i.e., good quality of the hyperthermia treatment sessions. Technical innovations may facilitate and improve clinical applications and should allow broad clinical implementations of IHT, e.g., intraoperative hyperthermia, and even intracavitary hyperthermia. From these experiences it would appear that IHT is an effective and safe treatment modality, especially when combined with radiotherapy for tumor palliation. Prospective randomized multicentric studies have already been initiated to investigate its role in palliative and adjuvant tumor therapy. PMID- 2198797 TI - Knowledge-based computer systems for radiotherapy planning. AB - Radiation therapy is one of the first areas of clinical medicine to utilize computers in support of routine clinical decision making. The role of the computer has evolved from simple dose calculations to elaborate interactive graphic three-dimensional simulations. These simulations can combine external irradiation from megavoltage photons, electrons, and particle beams with interstitial and intracavitary sources. With the flexibility and power of modern radiotherapy equipment and the ability of computer programs that simulate anything the machinery can do, we now face a challenge to utilize this capability to design more effective radiation treatments. How can we manage the increased complexity of sophisticated treatment planning? A promising approach will be to use artificial intelligence techniques to systematize our present knowledge about design of treatment plans, and to provide a framework for developing new treatment strategies. Far from replacing the physician, physicist, or dosimetrist, artificial intelligence-based software tools can assist the treatment planning team in producing more powerful and effective treatment plans. Research in progress using knowledge-based (AI) programming in treatment planning already has indicated the usefulness of such concepts as rule-based reasoning, hierarchical organization of knowledge, and reasoning from prototypes. Problems to be solved include how to handle continuously varying parameters and how to evaluate plans in order to direct improvements. PMID- 2198799 TI - Self-help groups at the turning point: emerging egalitarian alliances with the formal health care system? AB - Review of the historical development and current status of mutual aid self-help groups (SHGs) in the U.S. The SHGs social movements received an impetus from the 1987 Surgeon General's Workshop. Some alliances forming to link SHGs with the health care system are described. The Workshop recommended principles to guide these alliances. What direction will linkages actually take? Professional or bureaucratic cooptation and control of SHGs? Professionals can take a stand to respect SHG autonomy and self-determination. Professionals need training about SHGs. Research is needed on usefulness of experiential knowledge created and disseminated in SHGs and their social movement aspects. PMID- 2198800 TI - Comparisons of different debonding techniques for ceramic brackets: an in vitro study. Part I. Background and methods. AB - Techniques for removing metal orthodontic attachments are, for the most part, not as effective with ceramic brackets because the properties of ceramic brackets differ greatly from those of the conventional metal orthodontic brackets. Currently available ceramic brackets are composed of aluminum oxide crystals in either a polycrystalline or monocrystalline form that has a low fracture toughness compared with that of stainless steel. Metal brackets will deform 20% under stress before fracturing, whereas ceramic brackets will deform less than 1% before failing. The purpose of this study was (1) to evaluate the debonding characteristics of three different types of ceramic brackets when removed by techniques recommended by the manufacturers; (2) to evaluate and compare the conventional, ultrasonic, and electrothermal bracket-removal techniques, and (3) to evaluate and compare the mean enamel loss from removal by high-speed bur, by slow-speed bur, and by the ultrasonic method. In the first phase of the investigation, 140 teeth (70 maxillary central incisors and 70 third molars) were bonded with one of three types of ceramic brackets. Three different debonding methods were tested--(1) the conventional method recommended by the manufacturer (either pliers or wrench), (2) an ultrasonic method that employed specially designed tips, and (3) an electrothermal method involving an apparatus that transmits heat to the bracket. In each of the test groups, five variables were evaluated during and after bracket removal: (1) the incidence of bracket failure, (2) the amount of adhesive remaining after bracket removal, (3) the site of bond failure, (4) the debonding time for each technique, and (5) enamel damage resulting from bracket removal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198801 TI - Effects of phosphoric acid concentration and etch duration on enamel depth of etch: an in vitro study. AB - In a previous study we reported no significant differences among the shear bond strengths resulting from the application of an orthodontic bonding resin to enamel surfaces etched with three phosphoric acid (H3PO4) concentrations, each for three etch durations. The objective of the current study was to determine the depths of etch on ground enamel surfaces exposed to the nine etching procedures. The facial surfaces of 45 extracted human maxillary permanent central incisors were ground wet on 600-grit silicon carbide paper. Annular adhesive disks of 6 mm outer diameter and 3 mm inner diameter were positioned on the ground enamel surfaces and etched with 10 mm3 of 37%, 15%, and 5% H3PO4 for 60, 30, and 15 seconds, respectively. The calcium concentrations of the etching solutions were determined and the depths of etch calculated. The depths of etch were then measured with a surface profilometer. A stepwise decrease in the calculated depths of etch with decreasing acid concentration and duration of etching was obtained. The calculated etch depths ranged from 27.1 microns by etching with 37% H3PO4 for 60 seconds to 3.5 microns by etching with 5% H3PO4 for 15 seconds. The measured depths of etch followed a similar pattern. A highly significant correlation between calculated and measured depths of etch was obtained. PMID- 2198802 TI - A brief history of orthodontics. PMID- 2198803 TI - Legal aspects of orthodontic practice: risk management concepts. Ceramic bracket update. PMID- 2198804 TI - And the children shall teach us ... PMID- 2198805 TI - Carotid artery reconstruction following extracorporeal membrane oxygenation. AB - Right hemispheric brain injury has been noted in surviving infants treated with venoarterial extracorporeal membrane oxygenation (ECMO). This phenomenon may be secondary to permanent ligation of the right carotid artery. At our institution, conventional ventilatory therapy failed in five neonates with respiratory insufficiency, and they were treated successfully with ECMO. In four of the five neonates, the right carotid artery was reconstructed at the time of decannulation. At discharge, all newborns with carotid artery repair showed no signs of unilateral brain injury and had excellent antegrade flow in the right carotid artery as assessed by both duplex and transcranial Doppler ultrasound scanning. Carotid artery reconstruction after ECMO is a technically simple procedure that may reduce the incidence of right hemispheric brain injury and long-term consequences of marginal cerebral perfusion. PMID- 2198806 TI - Prolonged bacteremia with catheter-related central venous thrombosis. AB - Infection of a central venous thrombus is a serious but rarely recognized complication of the use of central venous catheters in children. We report the cases of seven children with persistent bacteremia or fungemia in which central venous thrombosis was demonstrated by ultrasonography after removal of the catheter. All patients had signs and symptoms of infection, but only one had clinical evidence of central venous stasis. Bacteremia persisted from 6 to 35 days. Infection did not resolve in any patient prior to catheter removal, and five patients had positive blood cultures for 5 or more days after removal of the catheter. Six patients, including all who survived, were treated parenterally with antibiotics for more than 28 days. Two patients died; neither death was directly attributable to infection. Central venous thrombosis should be suspected in patients with persistent catheter-related bacteremia. Optimal treatment of this problem is not yet known. PMID- 2198807 TI - A new combined trivalent live measles (AIK-C strain), mumps (Hoshino strain), and rubella (Takahashi strain) vaccine. Findings in clinical and laboratory studies. AB - Trivalent virus vaccine, containing measles AIK-C strain, mumps Hoshino strain, and rubella Takahashi strain, was administered to a total of 1369 healthy children, 8 months to 18 years of age. For comparative study, monovalent vaccines of AIK-C strain and Hoshino strain were administered to 147 and 122 initially seronegative children, respectively. The clinical and serological responses following vaccination were analyzed. Among the recipients of the trivalent vaccine, 893 were initially seronegative to all three viruses. Inoculation induced sufficient serological responses: 99.7% for measles and rubella viruses and 96.3% for mumps virus. The incidence of febrile reaction (greater than or equal to 37.5 degrees C axillary temperature) was low, 15.9%, and a temperature of 39.0 degrees C or higher occurred in only 1.3% of the subjects. The seroconversion rate, magnitude of antibody titers, and incidence of clinical reactions following the trivalent vaccination were similar to those occurring after the monovalent measles vaccination. PMID- 2198808 TI - Radiological case of the month. Idiopathic aortic thrombosis. PMID- 2198810 TI - Prophylaxis of asbestos-induced diseases: studies and perspectives. AB - In recent years, implementation of dust-suppressing measures in USSR asbestos mills has led to significant decrease in dust levels. New cases of asbestosis and asbestotuberculosis in annual medical examinations have not been detected. For prevention of possible future incidence of these diseases, we plan to concentrate efforts on the medical selection of new employees, taking into account not only dust exposure, but also other ascertained risk factors (social, demographic, and biological, especially genetic). It seems to us that the grounds for complete prohibition of asbestos are insufficient. Substitution with alternative materials is discussed. PMID- 2198811 TI - Enchondromatosis and hemangioma (Maffucci's syndrome) with orbital involvement. AB - Maffucci's syndrome is a rare, congenital disease of unknown cause characterized by the development of multiple enchondromas and soft-tissue hemangiomas. We treated a 34-year-old man with Maffucci's syndrome, bilateral proptosis secondary to multiple intraorbital hemangiomas, corneal exposure secondary to a left facial nerve palsy, and multiple intra-abdominal tumors. The skeletal manifestations were not clinically apparent and were only discovered after a careful radiologic survey. Simultaneous bilateral orbital cavernous hemangiomas should alert the physician to the possibility of Maffucci's syndrome. PMID- 2198809 TI - Mutations causing hemophilia B: direct estimate of the underlying rates of spontaneous germ-line transitions, transversions, and deletions in a human gene. AB - Spontaneous mutation provides the substrate for evolution on one hand and for genetic susceptibility to disease on the other hand. X-linked diseases such as hemophilia B offer an opportunity to examine recent germ-line mutations in humans. By utilizing the direct sequencing method of genomic amplification with transcript sequencing, eight regions (2.46 kb) of likely functional significance in the factor IX gene have been sequenced in a total of 60 consecutive, unrelated hemophiliacs. The high frequency of patient ascertainment from three regions in the midwestern United States and Canada suggests that the sample is representative of hemophiliacs of northern European descent. Twenty-six of the delineated mutations are reported herein, and the group of 60 is analyzed as a whole. From the pattern of mutations causing disease and from a knowledge of evolutionarily conserved amino acids, it is possible to reconstruct the underlying pattern of mutation and to calculate the mutation rates per base pair per generation for transitions (27 x 10(-10)), transversions (4.1 x 10(-10), and deletions (0.9 x 10(-10)) for a total mutation rate of 32 x 10(-10). The proportion of transitions at non-CpG nucleotides is elevated sevenfold over that expected if one base substitution were as likely as another. At the dinucleotide CpG, transitions are elevated 24-fold relative to transitions at other sites. The pattern of spontaneous mutations in factor IX resembles that observed in Escherichia coli when the data are corrected for ascertainment bias. The aggregate data hint that most mutations may be due to endogenous processes. The following additional conclusions emerge from the data: (1) Although in recent decades reproductive fitness in individuals with mild and moderate hemophilia has been approximately normal, the large number of different mutations found strongly suggest that these levels of disease substantially compromised reproduction in previous centuries. (2) Mutations which putatively affect splicing account for at least 13% of independent mutations, indicating that the division of the gene into eight exons presents a significant genetic cost for the organism. In one individual a "silent" mutation at lysine 5 is likely to cause hemophilia by generating a perfect splice donor consensus sequence in exon b. (3) All the missense mutations occurred at evolutionarily conserved amino acids. As additional data are generated on the pattern of mutations caused by specific mutagens, it will be possible to utilize the pattern of spontaneous mutation to estimate the maximal contribution of that mutagen during the past century. PMID- 2198812 TI - A double-masked three-month comparison between 0.25% betaxolol suspension and 0.5% betaxolol ophthalmic solution. AB - In 352 patients with primary open-angle glaucoma or ocular hypertension, a multicenter double-masked, parallel-group clinical study compared the effects on intraocular pressure and ocular comfort of 0.5% betaxolol ophthalmic solution, a cardioselective beta-adrenergic blocking agent, with 0.25% betaxolol suspension. With twice-daily dosages, baseline intraocular pressure was significantly reduced (P = .0005), with no significant difference between the two groups, at Week 2 and at Months 1, 2, and 3. Further, the prevalence of ocular discomfort upon topical instillation was significantly lower for 0.25% betaxolol suspension than for 0.5% betaxolol solution (P = .0005). PMID- 2198813 TI - Lymphocytic lymphoma of intermediate differentiation. Morphologic and immunophenotypic spectrum and clinical correlations. AB - All cases of lymphocytic lymphoma of intermediate differentiation (IDL) referred to the National Cancer Institute were reviewed in order to define the histopathologic spectrum of the disease and to investigate morphologic and immunophenotypic features with potential prognostic relevance. Thirty-three cases were classified as IDL according to histologic criteria. Immunophenotypic analysis was performed in 27 cases, and clinical records were available for 22 patients. The median age was 58 years, and the male-to-female ratio, 3.4:1. All patients presented with stage III or IV disease, and five had extranodal presentations. Median survival was 56.3 months, with only three patients having a prolonged relapse-free survival (greater than 2 years). Morphologically, 14 cases were diffuse or only vaguely nodular; 18 cases showed a mantle zone pattern with naked germinal centers. There was a trend toward prolonged median survival for patients with the mantle zone (77.4 months, p = 0.098). The neoplastic population was composed of irregular or cleaved small lymphoid cells with a mitotic rate ranging from 5 to 62 per 20 high-power fields (hpf). A histologically distinctive variant with blastic cytologic features was identified (seven cases). The blastic variant was associated with a higher mitotic index (51.3 versus 19.0) and shortened survival (24.9 months). In contrast to the histologic progression often observed in follicular lymphomas, in no case was transformation to a large-cell or small noncleaved lymphoma observed. All cases had a mature B-cell phenotype demonstrating monoclonal Ig and B-cell surface antigens. Seventy-eight percent were CD5 positive; three of six CD5-negative cases presented in mucosal associated extranodal sites. CD10 and CD25 were expressed in 52% and 44%, respectively, but did not show clinical correlations. The proliferative rate measured by Ki-67 positivity correlated with the mitotic index, but neither of these parameters had a statistically significant influence on survival. PMID- 2198814 TI - The 1989 Fred W. Stewart award. PMID- 2198816 TI - [Diagnosis, therapy and echographic monitoring of the treatment of girls with juvenile uterine bleeding]. AB - The study group included 49 patients aged 16 to 19 years with combined hemostatic and reproductive disorders (n = 26) and reproductive disease without hemostatic defects (n = 23). The study yielded a differential diagnostic protocol for juvenile uterine bleedings, pathogenetically relevant therapy and echographic monitoring of its efficacy. PMID- 2198815 TI - [Ovulation and proteolytic enzymes]. PMID- 2198817 TI - [Ultrasonic screening of a group at risk of developing ovarian tumors]. PMID- 2198818 TI - [Hyperprolactinemia and dysfunction of the reproductive system]. PMID- 2198819 TI - [Contributions of R. V. Kiparskii to the development of Soviet gynecology]. PMID- 2198820 TI - [Epidemiological method of studying obstetric-gynecologic diseases]. PMID- 2198821 TI - Clinical features and biological implications of acute mixed lineage (hybrid) leukemias. AB - The composite phenotype of a population of leukemic blast cells is derived through analysis of morphology, cytochemistry, cytogenetics, surface antigens, and gene structure. When analyzed in such a fashion, approximately 10-25% of childhood acute leukemias will show markers of more than one lineage; these may be coexpressed on individual cells (biphenotypic) or appear on two distinct blast populations (bilineal or biclonal). Occasionally, there is conversion from one leukemic phenotype at diagnosis to another phenotype at relapse (lineage shift). Mixed lineage features appear to have biologic and prognostic significance. Some specific mixed lineage leukemia syndromes have been identified; among them are acute nonlymphoid leukemia with T-lymphoid features, CD7+, CD4-, CD8- acute leukemia, CD2+/CD19+ acute lymphoid leukemia, and acute leukemias associated with specific cytogenetic markers, e.g., t(4;11) and t(9;22). In general, these forms of acute leukemia along with others with mixed lineage markers have a poor prognosis, and new therapeutic approaches appear to be indicated. PMID- 2198822 TI - Immunomodulation by intravenous immunoglobulin. AB - In 1980, it was observed in a child with idiopathic thrombocytopenic purpura (ITP) that intravenous administration of pooled human immunoglobulin-G (IVIG) was followed by a rapid increase of the platelet count. Prompted by this finding, a pilot study and two prospective multicenter studies on children with ITP were organized. Efficacy of this new treatment for ITP was soon confirmed worldwide. In addition to the immediate effect, long-term observations following administration of IVIG suggested the occurrence of modulation of the immune response. Also, concomitant with studies on the mechanism of action of IVIG, the use of IVIG in the treatment of patients with other immune-related disorders was explored. PMID- 2198823 TI - A retrospective review of undifferentiated malignancy in childhood. AB - We reviewed the experience of children with "undifferentiated" cancer at The Children's Hospital of Pittsburgh (CHP) from 1971 through 1987. Of 2,095 patients 0-18 years old with diagnoses during that time of any cancer, the initial CHP pathology report rendered a diagnosis in 22 children (1.1%) of "undifferentiated malignancy" or "malignant tumor" (15 cases), "undifferentiated carcinoma" (two cases) or "anaplastic tumor or carcinoma" not otherwise specified (five cases). A review of pathologic findings using current methods and immunostaining led to the assignment of a specific diagnosis in 15 of the 20 cases so studied. Thus, the incidence of undifferentiated cancer by current criteria was reduced to no more than 0.23%. Two of the five tumors for which an alternative diagnosis could not be established were described as "rhabdoid," but because it is not clear that these tumors fit into a single category they were still considered to be undifferentiated. Clinical features and management of the 22 cases including the five persistently diagnosed as undifferentiated malignancy were heterogeneous. In the face of reassigned diagnoses, a number of patients would likely have received different chemotherapy as well as radiation. Nonetheless, seven patients with malignancy show no evidence of disease (NED), including several whose therapy, given the current best diagnosis, would not be considered to have been optimal. We recommend that for patients undergoing biopsy of a tumor, sufficient material be obtained for extensive pathologic evaluation. In this way, the diagnosis of undifferentiated malignancy in children can be almost eliminated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198824 TI - Thyroid adenoma following treatment of acute lymphocytic leukemia. AB - Sequelae of the treatment of children with acute lymphocytic leukemia (ALL) include multiple effects on the endocrine system, especially as it relates to growth and puberty. Thyroid dysfunction, and in particular, the occurrence of thyroid neoplasia, has been only rarely described. We report the development of benign thyroid neoplasms in two patients 9 years following the diagnosis and treatment of ALL. Both patients were clinically and biochemically euthyroid with noncystic "cold" nodules found on thyroid scan. In light of these observations, and along with previous reports of malignant thyroid neoplasia in children with ALL, long-term careful observation of children successfully treated for ALL is indicated. PMID- 2198825 TI - Integration of biological and psychosocial research on alcoholism. AB - This paper weights the extent and potential of efforts to integrate biological and psychosocial research on alcoholism. It begins with a review of what is known in five crucial domains--pathophysiology, psychopathology, etiology and course, treatment, and prevention--that could facilitate this integration. It then considers, for the same five domains, the modest additional increments in knowledge that would markedly enhance the effectiveness of these integration efforts. The paper concludes with a brief discussion of how we might proceed from what we know to what we need to know in the further pursuit of biological psychosocial integration. PMID- 2198826 TI - Behavioral and subjective effects of ethanol: relationship to cerebral metabolism using PET. AB - This study examined the effects of ethanol on regional cerebral metabolic rate using positron emission tomography (PET). The study explored the relationship between the mood-altering effects of ethanol and its effects on regional cerebral glucose utilization (CMRglu) in eight healthy male volunteers. In the first phase of the study, the subjects participated in a behavioral preference procedure conducted in a recreational environment to determine their responses to ethanol (0.5 g/kg) in a naturalistic setting. They then participated in three PET sessions, receiving at three to seven day intervals, in counterbalanced order, placebo, 0.5 g/kg or 0.8 g/kg ethanol. PET scans were conducted using a PETT-VI scanner with F-18-2-fluoro-2-deoxyglucose (FDG) as the tracer. The mood-altering effects of ethanol were measured in both the naturalistic and the PET phases of the study. Ethanol produced comparable effects on mood in the naturalistic and the PET settings (i.e., increases in positive mood). The lower dose of ethanol produced variable effects on whole brain and regional CMRglu across subjects. There was some suggestion that certain regional metabolic changes after ethanol were correlated with subjective responses to the drug. The higher dose of ethanol decreased whole brain CMRglu in most subjects. All regions were affected about equally. It was concluded that the mood-altering effects of ethanol are not related in a simple manner to regional changes in CMRglu. PMID- 2198829 TI - The role of host factors in the severity of spotted fever and typhus rickettsioses. PMID- 2198827 TI - Neonate blood IgE levels on filter paper as indicators of atopic disease. AB - Measurements of IgE levels in the blood of neonates were investigated using filter paper for blood collection in mass screening of congenital metabolic disorders. Time-resolved fluoroimmunometric assay system for the measurement of filter paper blood IgE levels was also studied. In an analysis of the present results, IgE values of at least 0.015U/ml, the measurement limit, were considered as high. High IgE levels in filter paper blood were seen in 28 (7.2%) of the 389 cases. When the relation with serum IgE levels at 18 months of age was investigated in 134 of 389 subjects, high serum IgE levels were also found in about 86.7% of the subjects with high IgE levels in filter paper blood. In addition, when the relation between family history of atopic disease and presence of atopic disease in the first 18 months of age was investigated in 203 of the 389 subjects, about 90% of the subjects with a family history of atopic disease and high IgE levels in filter paper blood developed atopic disease. Since filter paper blood is routinely collected in Japan, IgE levels in this blood should be widely checked for the prediction of onset of atopic disease in infants. PMID- 2198830 TI - Induction of heat-shock proteins in Coxiella burnetii. PMID- 2198831 TI - Diagnosis of human ehrlichiosis with the indirect fluorescent antibody test: kinetics and specificity. PMID- 2198833 TI - Host factors in the severity of Q fever. AB - The author has reviewed different aspects of the role of immunocompetence in the development of Q fever. Coxiella burnetii lives within the phagolysosomes of infected cells. In animals, the immunosuppression caused by either cortisone or X irradiation reactivates Q fever. In humans, cases of Q fever are reported in immunocompromised hosts suffering from leukemia, cancer, and human immunodeficiency virus infection (AIDS). Similar data are reported with strict or facultative intracellular parasites living within the phagolysosome. Sporadic publications reported the appearance of auto-antibodies during Q fever which may change the clinical picture of the disease. The pathological findings of hepatitis diagnosed during acute Q fever and those with C. burnetii chronic endocarditis are quite different and may reflect a different immunological response to C. burnetii. These facts emphasize the importance of host factors in the clinical expression and outcome of Q fever. PMID- 2198832 TI - Poxvirus recombinant vaccines. AB - The poxvirus family, subfamily Chordopoxviridae, contains six genera. The basic criteria distinguishing membership in a genus is cross-neutralization and host range predilection. Members of the genus Orthopoxvirus (vaccinia) and of the genus Avipoxvirus (fowlpox) have been genetically engineered to express genes from heterologous pathogens, thus providing a means of assessing these recombinant viruses as live recombinant vaccines. Vaccinia virus recombinants which have a broad host range can be useful vectors for both human and veterinary applications, while fowlpox virus recombinants, with a host range restricted to avian species, provide useful vectors for application to poultry diseases. Significantly, avipoxviruses have also been shown to be useful as vaccinating vectors in non-avian species. The results presented in this paper were selected to provide the reader with a sense of the extensive potential present in recombinant poxviruses as live recombinant vaccine candidates. The broad host range of vaccinia vectors and the narrower host range of avipoxvirus provide interesting applications. The surprising results obtained in non-avian species with recombinant fowlpox viruses are quite intriguing. The ability to generate a recombinant live vaccine that can readily be amplified in tissue culture, yet is non-proliferative in vivo, provides unique properties and interesting potential applications. PMID- 2198834 TI - A structural and immunological comparison of rickettsial HSP60 antigens with those of other species. PMID- 2198835 TI - Characterization of the origin of DNA replication of the Coxiella burnetii chromosome. PMID- 2198836 TI - Similarity in pathogenic features in lung and peritoneal infection by Coxiella burnetii, typhus group rickettsiae, and Chlamydiae. PMID- 2198837 TI - Immunology. A state of the art lecture. PMID- 2198839 TI - Metabolic and endocrine actions of interleukin-1. Effects on insulin-resistant animals. PMID- 2198838 TI - The multisubunit interleukin-2 receptor. PMID- 2198840 TI - Interactions of HIV gp120 with the CD4 molecule on lymphocytes and in the nervous system. PMID- 2198841 TI - Opioid peptides. Immunological significance? PMID- 2198842 TI - The role of growth hormone in modulation of the immune response. AB - Growth hormone was originally discovered because of its ability to promote linear growth in rodents and humans. It is now known that this molecule also augments a number of activities of leukocytes, such as antibody synthesis, cytolytic activity of T lymphocytes, natural killer cell activity, differentiation of neutrophils, production of tumor necrosis factor-alpha (TNF-alpha), and the synthesis of a thymic hormone known as thymulin. We have shown that growth hormone mimics one action of interferon-gamma (IFN-gamma) by augmenting the production of superoxide anion by macrophages and neutrophils. Growth hormone also is synthesized by leukocytes, which creates the possibility that it may act locally as a cytokine in lymphoid tissue. These findings show that a hormone that was originally isolated from the pituitary gland is involved in regulating host defense responses of leukocytes. PMID- 2198843 TI - The effects of prior exposure to silicone on capsule formation, histology, and pressure. AB - Investigations into the effects of prior silicone exposure on subsequent capsule formation around silicone implants assume particular relevance in light of the exponential increase in the medical application of polymers such as silicone. The inert nature of silicone has been in question with regard to its effects on the immune system, specifically whether or not it may act as a hapten or antigen. The present study analyzes the effects of prior silicone exposure on subsequent capsule formation, histological consistency, and pressures when an animal is reexposed to a silicone implant. Twelve female Lewis rats (body weight 250 g) were randomly divided into two groups. Group 1 (n = 6) rats were subcutaneously injected with 2.5 ml of Freund's Complete Adjuvant, Group 2 (n = 6) rats were injected with an equal volume of adjuvant sonicated with silicone gel. At 4 weeks a gel-filled silicone implant was placed subcutaneously in each animal. Capsule pressures were obtained at 4 months and the capsules from 3 rats from Group 2 were excised and examined microscopically. Pressures were measured again at 8 months and all remaining capsules were excised and examined. No statistically significant differences were noted when comparing two profiles over time between silicone-exposed and nonexposed animals in regard to capsule thickness or capsule pressure. However, capsule pressures were significantly lower at 8 months than at 4 months in both groups (p less than 0.034). In this model, significant reductions in capsule pressure were noted in both groups over time, but prior exposure to silicone did not appear to alter capsule histology, thickness, or pressure. PMID- 2198844 TI - Fat embolism syndrome after liposuction: a case report and review of the literature. AB - There have been three previous case reports of fat embolism syndrome (FES) after lipectomy. We present a case of FES diagnosed by pulmonary angiography. It seems likely that there is an incidence of subclinical fat embolization after liposuction, but conservative patient selection and aggressive postoperative management can lessen the morbidity and mortality of FES. PMID- 2198846 TI - [Late antiquity constitutional historical and social-anthropologic observations of middle and north European populations at the time of population migrations]. AB - This review on reports of mostly late antique authors concerning the physical appearance of Teutonic and Nordic populations of the so-called "Volkerwanderungszeit" is part of an extensive study of possible nutritional effects on somatotypes in early periods of the German history. It is linked up with a similar study on Teutonics of protohistorical periods (Wurm 1986a). The authors of the late antique periods were again and again impressed by the comparatively tall and sturdy stature as well as by the permanent martial aggressiveness and the considerable population growth of Northern peoples. One can observe a marked social variability in the distribution of somatotypes, and one can suppose, too, that physical superiority was favourable to social rise. However, as compared with Roman soliders the Teutonic-Nordic warriors of the "Volkerwanderungszeit" were obviously inferior as far as permanent physical stress is concerned. This seems to be caused by nutritional differences. Furthermore, the repeatedly claimed inclination of Teutonic-Nordic populations to a considerable consumption of alcoholics seems also be due to nutritional factors. Hair and eye colour of these populations are described by the various antique authors in a different way. The reported geographical differences in the distribution of hair and eye colour seem to indicate considerable Celtic elements in certain populations, which originally were designed as Teutonics. Apart from that no clear anthropological differences were recorded between different populations of this period. PMID- 2198845 TI - [Environmental history as an anthropologic topic. Contribution to "chemical anthropology"]. AB - Human population history is firmly connected with temporal and regional changes of the environment. Whether natural or anthropogene, alteration of environmental features lead to changes of human life-style and to the development of adaptive strategies. The demand of resources for his subsistence has led man to diverse impacts on his environment since ever. Thus, environmental history is a scientific topic for anthropologists. The research potential of trace element studies of excavated human skeletons for the reconstruction of natural and socio cultural environments as well as for distribution patterns of hazardous substances is outlined for the European Middle Ages. The scientific value of unravelling past man/environment-interrelationships for both the historical and applied sciences and the place of any "chemical anthropology" within this context is discussed. PMID- 2198847 TI - [The life and work of Prof. Dr. Ales Hrdlicka]. PMID- 2198848 TI - Two enteric coated microspheres in cystic fibrosis. AB - In a randomised single blind crossover study in children with cystic fibrosis and pancreatic insufficiency, two enteric coated microsphere preparations of pancreatin were compared on a capsule for capsule basis, by measuring the coefficient of fat absorption, nitrogen excretion, weight change, and symptom scores after four weeks' treatment with each preparation. Thirty nine subjects were randomly allocated to receive Pancrease followed by Creon or vice versa. Each individual subject received the same number of capsules per day in each study period. Data from 27 children (Pancrease/Creon, n = 13 and Creon/Pancrease, n = 14) wer suitable for analysis. Results showed no significant differences between the two preparations in any variable studied. We conclude that there is no significant difference between Pancrease and Creon when compared on a capsule for capsule basis. PMID- 2198849 TI - Forty years ago. Coeliac disease. PMID- 2198850 TI - Self hypnotherapeutic treatment of habitual reflex vomiting. AB - A 9 year old boy with intractable postprandial reflex vomiting was taught a self hypnotherapy technique incorporating relaxation exercises, mental imagery, and suggestions of symptom relief. The sequence was recorded on a personal stereo cassette tape. Vomiting was completely eliminated within four weeks. At 12 month review vomiting had not recurred. PMID- 2198851 TI - [Chagas cardiomyopathy: a myth and a challenge]. PMID- 2198852 TI - [Arteriosclerosis obliterans. Treatment with angiotensin-converting enzyme inhibitors]. AB - We compare the effects of two of the main angiotensin convertase enzyme inhibitors, captopril and enalapril, aiming to evaluate their effects in the arterial circulation performance, micro-circulation, and changes in regional blood flow, assuming their property of lowering the angiotensin II blood levels, a very strong peripheral vasoconstrictor. We studied 22 patients: all of them with hypertension and/or skin ulcerations, dropping out those who had venous. They were evaluated periodically, clinically and with photoelectric plethysmography of lower extremities. To interpret the traces we designed an ideogram which gathered the plethysmographic behavior before and after the treatment. Nearly 80% showed considerable improvement in pain, functional capacity and plethysmographic traces patterns. healing of the ulcerations was achieved in all case. We propose some hypothesis to explain the good effect that we have observed. PMID- 2198853 TI - [Hemolytic anemia in patients with heart valve prosthesis]. AB - This article analyzes the historic evolution of the Starr-Edwards prosthesis manufacture and its association to hemolysis. It describes also the information related to bioprosthesis and hemolysis. The mechanisms involved in mechanical hemolysis are discussed (turbulent flux, red cells trapping, construction material and autoimmunity). Reviews the pathophysiology and criteria for clinical and laboratory diagnosis of hemolysis. We describe the value of the quantitation of unconjugated bilirubin, free plasmatic hemoglobin, DHL and it's DHL1 iso enzyme, methemalbumin and urinary hemosiderin for the specific diagnosis of this entity. Finally we comment on the utility of bed rest, cellular maturity inductors, propranolol and sulfinpyrazone therapy for the control of the hemolytic process. PMID- 2198854 TI - CCCVA, MANOVA, my black hen. Comments on repeated measures. PMID- 2198855 TI - Surreptitious noncompliance with oral fluphenazine in a voluntary inpatient population. PMID- 2198856 TI - Complex hemangiomas of infants and children. Individualized management in 22 cases. AB - Large hemangiomas in infants and children are rare but can be life-threatening if they involve vital structures or produce thrombocytopenia or congestive heart failure. During a 6-year period, 22 infants and children, aged newborn to 7 years, were treated for complex, symptomatic hemangiomas. The lesions were located in the liver in seven, face or parotid gland in five, neck in four, extremity in two, and mediastinum, chest wall-spinal cord, trachea, and retroperitoneum in one patient each. The diagnosis was suggested by physical examination in all patients and was confirmed by radiologic examination in most patients. The treatment was individualized, usually progressed from less to more invasive, and included observation, prednisone therapy, arterial ligation, and resection. All children were eventually cured, with minimal morbidity. Children with life-threatening hemangiomas can be successfully managed with the use of a variety of techniques. PMID- 2198857 TI - Unilateral neck exploration for primary hyperparathyroidism. AB - The operative approach to primary hyperparathyroidism due to a single adenoma remains controversial. We evaluated our experience with 75 patients presenting with primary hyperparathyroidism between January 1979 and September 1988. Prior to 1985 all patients underwent bilateral exploration. During this period, ultrasonographic localization in 6 patients proved highly accurate. Subsequently, routine preoperative ultrasonographic localization was used and patients were prospectively evaluated for the following: (1) incidence of unilateral exploration, (2) accuracy of ultrasonographic localization, (3) incidence of complications, and (4) operative time. Localization permitted unilateral exploration in 19 of 36 patients, although its accuracy depended on the interest of the radiologist involved. Institution A had an accuracy of 92%, while institution B had an accuracy of only 43%. There were fewer complications with unilateral exploration, and operative time was significantly less. Unilateral exploration based on preoperative ultrasonographic localization is recommended as the initial approach to primary hyperparathyroidism due to a single adenoma. PMID- 2198858 TI - Electron and immunoelectron microscopy of rabbit haemorrhagic disease virus (RHDV). AB - Rabbit haemorrhagic disease virus (RHDV) had a calicivirus-like structure and a diameter of 31.5-33.0 nm. Antigenic relationship between the investigated RHDV strain and the causal agent of RHD in China was demonstrated by immunoelectron microscopy. PMID- 2198859 TI - [Neurocysticercosis. II. Evaluation of treatment with praziquantel]. AB - The results of the use of praziquantel (PZQ) for the etiologic treatment of neurocysticercosis (NC) are presented. The drug was administered to 45 patients (24 women and 21 men) at increasing doses of 10 to 50 mg/kg/day during the first week and with maintenance on the last dose for two additional weeks, preferentially for patients that presented intraparenchymatous cystic lesions in the computed axial tomography. Follow-up ranged from 8 months to 4 years and a half (median, 2.7 years). During PZQ administration 27 patients (60%) presented side effects which required interruption of treatment in three cases. Decompensation of the increased ICP occurred in two cases (one of them fatal). Exacerbation of CSF pleocytosis occurred in 26 patients (57.7%). Evaluation of the results of PZQ treatment showed a lower clinical-laboratory rate of success than reported in the literature. The most appropriate indications for the use of PZQ are discussed on the basis of the present data and of reports by other investigators. In view of the risks and fallibility of treatment with PZQ, the solution of NC resides in the prevention of infestation. PMID- 2198860 TI - Hydrocele following placement of a ventriculoperitoneal shunt: case report. PMID- 2198861 TI - [Treatment of the carotid-cavernous fistula: a historical review]. PMID- 2198862 TI - [Myasthenia gravis: critical evaluation of the treatment]. AB - The author emphasizes the difficulty of the subject since on the one hand there is no assurance about the value of the treatment methods performed commonly at the moment, and on the other hand there is an evident lack of prospectively controlled trials and double-blind studies. Mostly this dilemma occurs by the lack at the moment of any specific treatment. The author deals with the four therapeutic methods most commonly used: cholinergic drugs, thymectomy, immunosuppressive drugs and plasmapheresis. At last, the experimental specific immunotherapy by the use of antibodies and suppressive cells and the irradiation methods are discussed. PMID- 2198864 TI - [Chronic subdural hematoma: surgical treatment and results in 96 patients]. AB - Ninety-six patients with chronic subdural hematoma were treated surgically and their clinical features presented in detail. Carotid angiography gave the correct diagnosis in all patients. CT scan was performed in 38 and was diagnostic in 92.1% of the cases. The clots were removed through burr-holes or small trephines: 78 (81.3%) patients were cured, 6 (6.2%) had permanent disabilities and 12 (12.5%) died. Operative mortality was related to the degree of neurological impairment, advanced age and systemic diseases. Neurologic sequelae were mostly related to reoperations due to recurrence of the hematoma and bilateral clots, as well. Low intracranial pressure syndrome with brain collapse was seen in 3 cases and treated with lumbar injection of saline solution. The delay in diagnosis and operation as cause of bad outcome is stressed. PMID- 2198863 TI - [Infantile hydrocephalus: long-term results in 102 patients and the importance of neurosonography]. AB - A personal series (in 94% of the cases) of 102 children who underwent 170 procedures (1.66 procedures/patient) for hydrocephalus has been followed for 5 1/2 years (Jan-83 to June-88). Most of the children were under two years of age (80%) and in these cases brain sonography was the examination of choice for both diagnosis and follow-up (307 examinations, 4.4 per patient). Only occasionally was computed tomography necessary for better study in these cases. Our results suggest that there was no significant difference between our cases and those published in the literature concerning the number or procedures/patient (1.66)., infection rate (5.2%), mortality rate (6.8%) and intellectual performance. We recommend the use of brain sonography both in diagnosis and follow-up studies for hydrocephalic children since this examination is innocuous, inexpensive and easy to perform by neurosurgeons. Also it provides a good interaction between the examiner, the child and the parents, which is of utmost importance for the comprehension of the disease by the parents and early diagnosis of complications by the neurosurgeon. PMID- 2198865 TI - Effects of parasympathectomy on androgen responses of the rat submandibular gland. AB - The effects of androgen on the activities of esteropeptidase and delta 4-3 ketosteroid 5 alpha-reductase were investigated. Ratios of the denervated side to the non-operated side for gland weight and esteropeptidase activity were higher in androgenized females than in untreated females. The specific activities of 5 alpha-reductase were increased by denervation but the total activities were decreased. The results suggest that parasympathectomy leads to higher androgen responsiveness in the rat submandibular gland, which relates to the observed reduction in weight loss of the gland and the increases in its esteropeptidase activities. PMID- 2198866 TI - Assay of ascorbic acid in human crevicular fluid from clinically healthy gingival sites by high-performance liquid chromatography. AB - The volume of fluid on filter paper strips was measured with a Periotron, eluted, and the ascorbic acid measured by chromatography. In preliminary experiments, pre impregnation of the strips with citric acid increased the recovery of standard ascorbic acid from 37 to 89% and significantly reduced loss of water from the strips over a 3 min period. Samples of crevicular fluid were then collected from clinically healthy gingival sites of 21 healthy volunteers using pre-impregnated strips and assayed for ascorbic acid concentration, together with samples of blood plasma. The mean ascorbic acid concentration in gingival crevicular fluid (207.3 mumol/l; SD: +/- 81.8) was significantly higher (p less than 0.001) than the corresponding plasma concentration (mean 72 mumol/l; SD: +/- 23.3). PMID- 2198867 TI - A simple regression model for estimating gestational age in later pregnancy by ultrasonography. AB - Three hundred and six antenatal women with confirmed LMP underwent a single real time ultrasonographic examination between 32-40 weeks of gestation. Four parameters viz. BPD, HL, FL and AP having a positive correlation with gestational age were studied. A multiple regression model for predicting gestational age by a single ultrasonographic examination was developed by forward selection method after eliminating multicollinearity; as a high degree of intercorrelation was found between FL and HL, HL was eliminated from the data. The BPD does not have a significant role in predicting gestational age in later pregnancy. The proposed regression equation with FL and AP predicts gestational age 75% of time within +/ 10 days of 95% confidence limit. PMID- 2198868 TI - Comparative efficacy of crystalline and amorphous oxfendazole in sheep. PMID- 2198870 TI - [Are cialit-preserved ossicles as middle ear implants still bacteriologically defensible? Their replacement by pre-formed implants fashioned from teeth]. AB - Recent studies have demonstrated a limited bactericidal activity of Cialit in the preservation of otologic transplants. The authors therefore performed several tests following routine treatment of the grafts. First, the contamination of allogenic ossicles was studied; afterwards, the bactericidal activity of Cialit was tested against standardized germs and clinical isolates. At the highly toxic concentration of 1:2000, Cialit is bactericidal. For clinical purposes, however, the less toxic solution of 1:5000 is generally used, which is not sufficiently safe against certain resistant clinical isolates. The fact that the activity of Cialit depends on its concentration explains the controversial findings in the literature. Furthermore, it is doubtful whether a weaker solution would prevent transmission of an HIV or hepatitis infection. Therefore, the authors recommend the autoclaving of otologic allografts. This also has forensic reasons; for example if the serologic status of the donor is unknown. As ossicles become brittle under this procedure, the authors now use sculptured parts of teeth, in which the hydroxyl-apatite is much more compact. The preformed prostheses can be autoclaved without problem. More than 150 reconstructions have proved the acceptance of this cheap implant material. Furthermore, forensic problems with ossicles from corpses do not arise. PMID- 2198869 TI - Nucleus basalis magnocellularis and memory: differential effects of two neurotoxins. AB - Although the cholinergic system is involved in memory, noncholinergic systems may also contribute to memory. Lesions of the nucleus basalis magnocellularis (NBM) produce behavioral impairments and reduction of cholinergic markers in the frontal cortex (FC). The present study compared the behavioral effects of lesions made with two different neurotoxins, ibotenic (IBO) acid and quisqualic (QUIS) acid. IBO or QUIS was injected into the NBM, and rats were tested in three different tasks: cued delayed nonmatch-to-sample (CDNMS), spatial delayed nonmatch-to-sample (SDNMS), and spatial two-choice simultaneous discrimination (STCSD). IBO producted a greater behavioral impairment than QUIS in the CDNMS and the SDNMS, although QUIS produced a greater drop in choline acetyltransferase (ChAT) activity in the cortex than IBO. At the end of behavioral testing, IBO rats, but not QUIS rats, were impaired in the retention of both tasks. The fact that QUIS lesions produced a greater loss of NBM cholinergic neurons, as determined by decreased ChAT activity, but less of a behavioral impairment in both a spatial and nonspatial task, suggests that the loss of noncholinergic NBM neurons must contribute to the memory impairments following NBM cell loss. PMID- 2198871 TI - Determination of catabolism of the photosystem II D 1 subunit by structural motifs in the polypeptide sequence. AB - Proteolytic mapping of the D 1 subunit of photosystem two and a degradation product which arises during its rapid catabolism shows that the latter is a result of proteolysis within the peptide motif QEEET. This motif is located in a portion of the D 1 protein thought to form a stroma-exposed connection between fourth and fifth transmembrane segments. This connection domain also contains a "PEST"-like sequence and forms part of the QB/herbicide binding niche. The QEEET motif seems to provide a major epitope in immunological studies, as judged from reaction of D 1 and its fragments with polyclonal antibodies. Antibodies against D 1 were found to react with other animal and plant proteins which contain similar sequence motifs. PMID- 2198872 TI - Photoinactivation of photosystem II and degradation of the D 1 protein are reduced in a cytochrome b6/f-less mutant of Chlamydomonas reinhardtii. AB - The effect of unoccupancy of the QB site by plastoquinone on the photoinactivation of reaction center II in a Cyt b6/f-less mutant of Chlamydomonas reinhardtii, B6, was investigated. In these cells the oxidation of plastoquinol generated by electron flow via RC II to plastoquinone and thus the turnover of PQH2/PQ via the QB site are drastically reduced. Reaction center II of the mutant cells was resistant to photoinactivation relative to the control cells as demonstrated by measurements of light-induced destabilization of S2-QB- charge recombination, rise in intrinsic fluorescence and loss of variable fluorescence. These parameters relate to functions involving the reaction center II D 1 protein. The light-induced degradation of D 1 in the mutant cells was also considerably reduced, with a t1/2 value of 7 h as compared, under similar conditions, to about 1.5 h for the control cells. These results indicate that the photoinactivation of RC II and turnover of the D 1 protein are related and require occupancy of the QB site by PQ and its light-driven reduction. PMID- 2198874 TI - Sequence analysis of four atrazine-resistant mutants from Rhodopseudomonas viridis. AB - Four atrazine-resistant mutants from the purple bacterium Rhodopseudomonas viridis were isolated. Sequence analysis revealed three different mutant strains carrying mutations in the herbicide-binding pocket: i) MAV 2: L212-Glu----Lys, ii) MAV 3: L216-Phe----Ser and iii) MAV 4 = MAV 5: L217-Arg----His, L220-Val--- Leu. Except MAV 3 all Rps. viridis mutants are different from those selected by their resistance towards the closely related triazine terbutryn. PMID- 2198873 TI - First glance on the three-dimensional structure of the photosynthetic reaction center from a herbicide-resistant Rhodopseudomonas viridis mutant. AB - A first model of the three-dimensional structure of the photosynthetic reaction center of the mutant T1 (SerL223----Ala, ArgL217----His) from Rhodopseudomonas viridis, resistant toward the triazine herbicide terbutryn (2-methylthio-4 ethylamino-6-t-butylamino-s-triazine), has been developed from X-ray data measured to a resolution of 2.5 A. The secondary quinone, QB, which in T1 binds better than in the wild type, is present in the crystals. Both substituted residues are clearly visible in the difference fourier map. The replacement of these two residues in the QB site causes only minor changes in the overall structure of the protein. PMID- 2198875 TI - Cobamide-dependent methyl transferases. PMID- 2198876 TI - Aluminum, a neurotoxin which affects diverse metabolic reactions. AB - Experimental evidence is summarized to support the hypothesis that chronic exposure to low levels of aluminum may lead to neurological disorders. These disorders result from defective phosphorylation--dephosphorylation reactions, reduced glucose utilization and site-specific damage inflicted by free radicals produced by altered iron metabolism. The brain is a highly compartmentalized organ. Therefore, a co-localization of critical mass of metabolic errors rather than a single event may be essential to precipitate a neural disease. Aluminum appears to participate in formulating this critical mass. Patients with dialysis dementia get partial relief by desferroxamine which chelates aluminum. However, it also chelates iron and therefore limits its applicability. While the specific chelator for aluminum is yet to be made available, exercising a caution in aluminum intake appears prudent. PMID- 2198877 TI - Mechanisms of metal ion incorporation into metalloproteins. AB - Although the structure and function of protein metallocenters have been extensively characterized, much less is known about their assembly. Here, I describe several general strategies for metallocenter biosynthesis and provide literature precedents for each mechanism. The simplest mechanism involves reversible metal ion binding to amino acid ligands of the apo-protein. In a variation of this mechanism, the apo-protein first must be phosphorylated, carboxylated or otherwise covalently modified in order to create the metal ion binding site. Alternatively, passive metal ion binding may require the presence of an associated compound, such as a nucleotide, carbonate or inorganic sulfide, which is co-incorporated into the protein along with the metal ion. In addition, reversible binding may occur using a pre-formed organometallic cofactor such as a metal-tetrapyrrole. Electron transfer reactions are coupled to biosynthesis of certain metallocenters, i.e. oxidation or reduction of the metallocenter or apo protein may be required prior to binding, or once bound the metallocenter may be oxidatively trapped in the protein. An effector molecule may bind to apo-protein to open up or stabilize the metallocenter binding site, then after the metallocenter is incorporated the effector molecule dissociates. A transferase or insertase protein first may bind the metallocenter and then incorporate it into the appropriate apo-protein. Finally, metal cofactors may be covalently attached to proteins. Regardless of the metallocenter biosynthetic mechanism, intracellular metal ion concentrations must be sufficient; hence, metal ion transport systems also are briefly discussed. PMID- 2198878 TI - Characterization of the recombinant Clostridium pasteurianum ferredoxin and comparison of its properties with those of the native protein. AB - Ferredoxins (Fds) constitute an important class of nonheme iron-sulfur proteins. One of the most studied Fds is the [8Fe-8S] Fd from Clostridium pasteurianum. The gene for this Fd has previously been cloned and sequenced. We report the expression of this Fd in Escherichia coli, and the characterization and comparison of this recombinant protein to the native Fd. We have found that the purified recombinant protein has the same enzymatic, redox, magnetic and electronic properties as the native Fd isolated from C. pasteurianum, which indicates that the two [4Fe-4S] clusters present in the Fd were correctly formed in E. coli. PMID- 2198879 TI - Pregnancy-blocking progesterone antibody targets specifically the uterus through its progesterone-binding sites. AB - Passive immunization with a mouse monoclonal antibody against progesterone, designated DB3, blocks pregnancy in several species. We have previously reported that DB3 localizes in the mouse uterine epithelium shortly before normal implantation. This phenomenon is pregnancy dependent and specific for the progesterone antibody. In this study we demonstrate that DB3 is present in the lumen of the uterus 36 h after an i.p. injection; this correlates with the time of maximum antibody reaction on the uterine epithelium. Incubation of DB3 with free progesterone, progesterone-hemisuccinate or progesterone-bovine serum albumin before administration prevented its localization on the epithelium, indicating that the localization requires free progesterone-binding sites and thus probably depends upon progesterone binding. In addition, studies in vitro show that DB3 can effectively bind to progesterone carried by high-affinity progesterone-binding protein purified from coypu plasma. We suggest that specific targeting of DB3 may be through progesterone associated with a progesterone binding molecule on the membrane of the uterine epithelia. This may be an important part of the mechanism of antibody action against implantation. PMID- 2198880 TI - [Adhesion molecules: their potential implication for dermatology]. AB - Many biological events involve an initial stage of adhesion. The molecules that are responsible for the process of adhesion have been studied extensively in recent years. The most widespread receptors taking part in cell-external matrix and cell-cell reactions are from the families of integrins and immunogloblins. In normal skin, the keratinocytes and fibroblasts essentially express beta 1 (VLA) receptors and the cells of Langerhans the beta 2 receptors of the integrin family. Their pathological modification is under study. In contrast, involvement of the ICAM-1 molecule (ligand of receptor LFA-1) in pathology seems to be considerable. ICAM-1 is expressed by keratinocytes in many benign and malignant skin diseases and this makes possible interaction with LFA-1 lymphocytes. The passage of lymphocytes towards the epidermis is the basis of all inflammatory and immune reactions and is dependent on adhesion molecules. It will doubtless, in the future, be possible to explain the physiopathology of inflammatory skin reactions in terms of excessive expression or insufficient ICAM-1 by pathological keratinocytes. PMID- 2198881 TI - [Lyell syndrome and its attributability to medications: methodological problems]. AB - Lyell's syndrome, the most serious of the secondary effects of drugs, is a good example of difficult methodology in the establishment of a causal link between the observed accident and a particular drug (association). In each patient, in the absence of a reliable test, in vivo or in vitro, this association rests on a probability step based on comparison of essentially chronological criteria. On a country scale, accumulation of cases attributed to one product only allows a calculation of the risks if the number is known of the patients exposed to the drug. It is possible to make only indirect estimations of this "denominator", calculated from the sales figures. Only prospective epidemiological studies by the method "cases/controls" permits rigorous calculation of the risks of the drugs implicated in the etiology of Lyell's syndrome. They do not control the problem of association in individual cases. PMID- 2198882 TI - [Allergy to dermocorticoids]. PMID- 2198883 TI - The applications and future implications of bitterness reduction and inhibition in food products. AB - Numerous food and beverage products, bulking agents, and pharmaceuticals have pleasant as well as unpleasant bitter-tasting components in their taste profile. In numerous cases, the bitter taste modality is an undesirable trait of the product. Bitter characteristics found in some food systems have been removed or diminished by various known processes, but no universally applicable bitter inhibitor has ever been recognized. Some indications point to a receptor-mediated phenomenon for sweetness and bitterness. Research on sweet compounds has led to knowledge of sweetness inhibitors and could ultimately lead to bitterness inhibitors. To facilitate efforts to rationally design a universal bitter inhibitor or cocktail of such, a review of the bitter taste phenomena and known methods of bitterness reduction and inhibition have been compiled. PMID- 2198884 TI - The formation and properties of wheat flour doughs. AB - Among the cereal flours, only wheat flour will form a viscoelastic dough when mixed with water. The viscoelasticity appears to be because the gluten proteins are water compatible and thus will swell and interact. The gluten protein's large molecular size and low charge density appear to allow them to interact by both hydrogen and hydrophobic bonds. Wheat flour doughs are also unique in their ability to retain gas. This property appears to result from a slow rate of gas diffusion in the dough. The third major unique property of wheat flour doughs is their ability to set in the oven during baking, and thereby to produce a rigid loaf of bread. Although not clearly understood, this appears to be a heat-induced crosslinking of the gluten proteins. PMID- 2198885 TI - Binding of the bovine basic pancreatic trypsin inhibitor (Kunitz inhibitor) to human and bovine factor Xa. A thermodynamic study. AB - The effect of pH and temperature on the apparent association equilibrium constant (Ka) for the binding of the bovine basic pancreatic trypsin inhibitor (BPTI, Kunitz inhibitor) to human and bovine factor Xa (Stuart-Prower factor; EC 3.4.21.6) has been investigated. Under all the experimental conditions, values of Ka for BPTI binding to human and bovine factor Xa are identical. On lowering the pH from 9.5 to 4.5, values of Ka (at 21.0 degrees C) for BPTI binding to human and bovine factor Xa decrease, thus reflecting the acidic pK shift of the His57 catalytic residue from 7.1, in the free enzyme, to 5.2, in the proteinase inhibitor complex. At pH 8.0, values of the apparent thermodynamic parameters for BPTI binding to human and bovine factor Xa are: Ka = 2.1 x 10(5)M-1 (at 21.0 degrees C), delta G degree = -29.7 kJ/mol (at 21.0 degrees C), delta S degree = +161 entropy units (at 21.0 degrees C), and delta H degree = +17.6 kJ/mol (temperature-independent over the explored range, from 5.0 degrees C to 45.0 degrees C). Thermodynamics of BPTI binding to human and bovine factor Xa have been analysed in parallel with those of related serine (pro)enzyme/Kazal- and /Kunitz-type inhibitor systems. Considering the known molecular models, the observed binding behaviour of BPTI to human and bovine factor Xa was related to the inferred stereochemistry of the proteinase/inhibitor contact region. PMID- 2198886 TI - Mechanism of the inhibition by insulin of the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene in rat hepatocyte cultures. Action on gene transcription, mRNA level and -stability as well as hysteresis effect. AB - The mechanism of the antagonistic action of insulin on the glucagon-dependent stimulation of the phosphoenolpyruvate carboxykinase (PEPCK) gene was studied in primary cultures of rat hepatocytes. Gene expression was monitored by the transcriptional activity of the PEPCK gene and the accumulation and degradation of PEPCK mRNA. 1) Insulin in concentrations from 0.1 to 100nM shifted the dose response curve of the glucagon-dependent accumulation of PEPCK mRNA to the right, increasing the half-maximally effective glucagon concentration gradually from 0.1 to 0.7nM. At saturating 10nM glucagon concentrations insulin was not antagonistic. 2) Glucagon at 0.1nM concentrations increased PEPCK gene transcription and PEPCK mRNA to a transient maximum at 0.5 and 2 h, respectively. Insulin, added at 10nM concentrations simultaneously with glucagon, reduced the maximal increase in PEPCK gene transcription by 70% and in PEPCK mRNA by 45%, respectively. 3) Following the maximal glucagon-induced increase after 2 h PEPCK mRNA declined to half-maximal levels after another 2.3 h. Insulin, added at 2 h at the PEPCK mRNA maximum, accelerated the disappearance of PEPCK mRNA, which reached half-maximal values already after another 1.2 h. 4) The transcriptional inhibitor cordycepin, added at 2 h at the PEPCK mRNA maximum, clearly retarded the normal and the insulin-accelerated decay of PEPCK mRNA so that half-maximal levels were reached only after another 5 h and 3 h, respectively. However, cordycepin did not retard the decay of PEPCK mRNA, when insulin was present from the beginning of induction by glucagon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198887 TI - Intensity-based domain refinement of oriented but unpositioned molecular replacement models. AB - A program is described that performs least-squares group refinement of oriented molecular replacement models whose positions in the unit cell are unknown. The program (INTREF) is designed to produce improved models for use in a translation function by optimizing the orientations and relative translations of the model domains. The molecular contents of the asymmetric unit are refined as a small number of rigid bodies whose origins relative to each other may be unknown. More than one molecule in the asymmetric unit can be accommodated. The refinement seeks to minimize the residual error between the observed and calculated intensities that have been modified to produce the equivalent of a radial weighting in Patterson space. Calculated intensities include contributions from all symmetry-related molecules, enabling meaningful refinement in high-symmetry space groups. Derivatives of the intensities with respect to the rigid-body parameters are evaluated numerically using fast Fourier transforms and the shifts are obtained by non-linear least-squares analysis. Results with test cases show that the program is capable of adjusting the orientations and relative translations of protein domains to give models that more closely resemble the known structures. Consequently, the resulting models produce more accurate and more interpretable results in translation functions. The importance of including all crystallographically related molecules and of downweighting the contribution of the longer-radius region of the Patterson function is demonstrated. PMID- 2198888 TI - Long-term continuous ambulatory peritoneal dialysis. Mass transfer and nutritional and metabolic stability. AB - Long-term mass transfer and nutritional and metabolic stability of end-stage renal disease patients maintained on continuous ambulatory peritoneal dialysis (CAPD) continue to be of concern. This study longitudinally monitored 43 Japanese CAPD patients (29 males, 14 females) from three centres within the Tokyo Metropolitan Area for an average period of 15 +/- (SD) 8 months. The mean time for patients on CAPD at study initiation was 18 +/- 15 months. Monitored parameters included urea and creatinine mass transfer coefficients, clearances and blood levels, ultrafiltration, lipid levels, dietary protein intake, and weight. Lipid data were also gathered retrospectively from patient records from the time of CAPD initiation. The results were analyzed using regression growth curve analysis and analysis of variance. Statistically significant linear rises with time were apparent only for the creatinine mass transfer coefficients, although this was not considered clinically significant in terms of changes either in peritoneal creatinine clearances or ultrafiltration. Serum cholesterol levels were found to rise significantly above pre-dialysis levels 11 months after CAPD onset, thereafter returning to levels not significantly above baseline levels. In summary, CAPD provided stable, acceptable treatment over the study period. PMID- 2198889 TI - Evaluation of a new polyamide membrane (Polyflux 130) in high-flux dialysis. AB - Removal of beta 2-microglobulin has become a major objective of dialysis therapy. The present study was performed to evaluate both compatibility and elimination capacity for beta 2-microglobulin of a newly developed high-flux polyamide membrane (Polyflux 130) during hemodialysis. The degree of leukopenia was moderate (-22%) and comparable with Polysulfone 600 (-25%). C3a desarg generation had a tendency to be lower with the Polyflux 130 membrane, and C5a desarg formation was identical with both types of membranes. As for degranulation of polymorphonuclear leukocytes, plasma elastase levels increased by 209% with Polyflux 130 and by 160% with Polysulfone 600 membranes. Likewise, plasma lactoferrin values rose during hemodialysis by 233% (Polyflux 130) and 160% (Polysulfone 600). The differences between membranes, however, were statistically not significant. There was a sharp drop in the serum levels of beta 2 microglobulin during dialysis with both membranes (Polyflux 130: -46%; Polysulfone 600: -48%). Accordingly, sieving coefficients were calculated to be 0.77 +/- 0.06 for Polyflux 130 and 0.80 +/- 0.06 for the Polysulfone 600 membrane. Both membranes were capable to remove large quantities of beta 2 microglobulin, amounting to 235 +/- 11 and 250 +/- 10 mg/4 h of dialysis for Polyflux 130 and Polysulfone 600, respectively. PMID- 2198890 TI - Intradialytic body weight changes and dialyzer pore size as main contributing factors to the evolution of beta-2-microglobulin in dialysis. AB - Cuprophane hemodialysis is associated with an early fall of leukocyte counts and an intradialytic rise in serum beta 2-microglobulin (beta 2M), in contrast to dialysis with more compatible dialyzers. It has been suggested that these two phenomena may be related. This study sets out to verify this hypothesis by comparing the evolution of leukocyte counts with that of beta 2M: (1) during dialysis with 5 dialyzer types with different pore size and/or leukocyte biocompatibility; (2) during first use and reuse of 3 dialyzer types, and (3) during sequential ultrafiltration and dialysis with cuprophane. In first-use dialyses, no relation could be found between changes in leukocyte counts and the evolution of beta 2M levels. Reuse of cuprophane and saponified cellulose ester resulted in a marked attenuation of the intradialytic fall in leukocyte counts after 15 min (change in white blood cell count: -72 and -17% for first-use and third-reuse cuprophane, -72 and -23% for saponified cellulose, respectively), but had no influence on the increase in beta 2M. Correlation studies of these data revealed that the intradialytic evolution of beta 2M was related to membrane pore size and, for membranes with a small pore size, to the intradialytic fluid losses: first-use cuprophane (p less than 0.05), saponified cellulose ester (p less than 0.001) and hemophane (p less than 0.01), and pooled first-use and reuse cuprophane and saponified cellulose ester (p less than 0.001). Cuprophane dialysis without ultrafiltration (dialysate Na+: 138 and 132 mEq/l) caused a fall in leukocytes, but induced no rise in beta 2M. Ultrafiltration with cuprophane either preceding or following dialysis consistently caused a rise in serum beta 2M, although a fall in leukocyte counts only occurred in the first case. Our data point away from a relationship between membrane biocompatibility, expressed as changes in leukocyte counts, and beta 2M concentration during hemodialysis. The major contributing factors appear to be dialytic fluid losses and membrane pore size. PMID- 2198891 TI - Stereotactic radiosurgery for acoustic neuromas. PMID- 2198892 TI - Image-guided needle biopsy of inaccessible head and neck lesions. AB - Fine-needle biopsy and large-needle core biopsy of inaccessible and deep-space lesions of the head and neck are difficult and sometimes hazardous to perform. Patients subsequently may have to undergo a major surgical procedure with exploration of the neck and open biopsy. We describe our experience with computed tomography and ultrasound-guided fine-needle and core-needle biopsy for 11 patients with inaccessible lesions in the head and neck. Carcinoma was diagnosed in three patients and nonmalignant pathologic findings in eight patients. Three of the needle biopsy findings were confirmed by surgical excision. The initial diagnoses made from the cytopathologic findings have remained unchanged in all patients. Compared with the alternative of open biopsy, we have found this method to be technically easy, diagnostically expeditious, and safe. Head and neck surgical oncologists should be familiar with image-guided biopsy techniques, since many of their patients may benefit from these diagnostic procedures. PMID- 2198893 TI - Total human exposure: basic concepts, EPA field studies, and future research needs. AB - Historically, environmental regulatory programs designed to protect public health have monitored pollutants only in geophysical carrier media (for example, outdoor air, streams, soil). Field studies have identified a gap between the levels observed in geophysical carrier media and the concentrations with which people actually come into contact: their daily exposures. A new approach--Total Human Exposure (THE)--has evolved to fill this gap and provide the critical data needed for accurately assessing public health risk. The THE approach considers a three dimensional "bubble" around each person and measures the concentrations of all pollutants contacting that bubble, either through the air, food, water, or skin. Two basic THE approaches have emerged: (1) the direct approach using probability samples of populations and measuring pollutant concentrations in the food eaten, air breathed, water drunk, and skin contacted; and (2) the indirect approach using human activity pattern-exposure models to predict population exposure distributions. Using the direct approach, EPA has conducted over 20 field studies for pollutants representing four groups--volatile organic compounds, carbon monoxide, pesticides, and particles--in 15 cities in 12 states. The indirect modeling approach has been applied to several of these pollutants. Additional research is needed in a great variety of areas. Even from the few projects completed thus far, the THE approach has yielded a rich new data base for risk assessments and has provided many surprises about the relative contribution of various pollutant sources to public health risk. PMID- 2198894 TI - Lymphocytes in the lung: should we continue to exalt only BALT? PMID- 2198895 TI - Specific binding of endothelin on human bronchial smooth muscle cells in culture and secretion of endothelin-like material from bronchial epithelial cells. AB - Endothelin, synthesized by endothelial cells, is the most potent vasoconstrictor and bronchoconstrictor agent known. We investigated endothelin release from human bronchial epithelial cells and the binding of the peptide to autologous bronchial smooth muscle cells in culture. Epithelial and smooth muscle cells were isolated by enzymatic digestion of bronchial tissue obtained on surgery, and cultured to confluency by standard methods. Epithelial cells stained positively for cytokeratin filaments. Smooth muscle cells stained uniformly for alpha-smooth muscle actin. Immunoreactive endothelin contents in the supernatants of epithelial cells extracted on C8 Amprep columns were evaluated by radioimmunoassay. Epithelial cells released appreciable amounts of immunoreactive endothelin into the culture medium (from 0.65 to 2.1 pmol/ml). A single specific binding site for [125I]endothelin 1 was identified on bronchial smooth muscle cells with an apparent Kd of 113 pM and a maximal binding capacity of 22.1 fmol/10(6) cells. At room temperature the binding was saturable, reached equilibrium at 120 min (25 pM endothelin 1), and was slowly and incompletely reversed by unlabeled endothelin over a period of 8 h. Conditioned medium from epithelial cells inhibited the [125I]endothelin 1 binding, dose dependently, and the effect was antagonized by monospecific antiserum. Thus, human bronchial smooth muscle cells possess specific binding sites for endothelin 1 and human bronchial epithelial cells secrete an endothelin-like material. This may have a role in the pathogenesis of asthma. PMID- 2198896 TI - Chromatin structure and gene activity. PMID- 2198897 TI - Centromeres and kinetochores: integrated domains on eukaryotic chromosomes. PMID- 2198898 TI - Gene transcription: basal and regulated transcription by RNA polymerase II. PMID- 2198899 TI - The myb and myc nuclear oncogenes as transcriptional activators. PMID- 2198900 TI - Chloroplast gene regulation: interaction of the nuclear and chloroplast genomes in the expression of photosynthetic proteins. PMID- 2198901 TI - The nuclear envelope and nuclear transport. PMID- 2198902 TI - The nucleolus and ribosome formation. PMID- 2198903 TI - Nucleus and gene expression. PMID- 2198904 TI - Novel UGA-suppressors in Escherichia coli K-12. AB - UGA-specific nonsense suppressors from Escherichia coli K-12 were isolated and characterized. One of them (Su+UGA-11) was identified as a mutant of the prfB gene for the peptide releasing factor RF2. It appears that in this strain, while peptide release at sites of UGA mutations is retarded, the UGA stop codon is read through even in the absence of a tRNA suppressor, exhibiting a novel type of passive nonsense suppression. Three suppressors (Su+UGA-12, -16 and -34) were capable of restoring the streptomycin sensitive phenotype in resistant bacteria (strAr). Because of their drug-related phenotype, these are possibly mutations in the components of the ribosomal machinery, particularly those concerned with peptide release at UGA nonsense codons. A tRNA suppressor was also obtained which was derived from the tRNA(Trp) gene. In this strain, a long region between rrnC (84.5 min) and rrnB (89.5 min) was duplicated and one of the duplicated genes of tRNA(Trp) was mutated to the suppressor. The mechanism of UGA-suppression is discussed in terms of translation termination at the nonsense codon in both active and passive fashions. PMID- 2198905 TI - [Hemangiomatous lesions with lymphangiectasias in the large intestine]. AB - We present the case of a 16 year-old male who presented intestinal hemorrhages since childhood; he was operated in emergency for microhemangiomas located in sigmoid colon and rectum. This lesion can be considered as a complex vascular hamartoma. We review the literature and discuss the differences between this lesion and angiodysplasia. PMID- 2198906 TI - [Immune thrombocytopenia and HIV-1 infection. Response to splenectomy]. AB - We present a case of thrombocytopenic purpura associated to acquired immunodeficiency; this disease is very infrequently associated to AIDS; the clinical characteristics are similar to the classical Idiopathic Thrombocytopenic Purpura, including the response to splenectomy. We discuss the therapeutic approach of this condition and review the literature, adding this new case of a patient with AIDS, Walter and Reed's stage II, who responded to splenectomy. PMID- 2198907 TI - [Medical treatment of cholelithiasis (II)]. AB - In the second part of this paper we review the potential side effects of orally administrated bile acids as well as recurrences after dissolution. We also discuss two new methods of medical treatment for cholelithiasis: the percutaneous instillation of contact solvents, particularly methyl-tert-butyl-ether and lithotripsy with external shock waves. PMID- 2198908 TI - Preoperative sedation before regional anaesthesia: comparison between zolpidem, midazolam and placebo. AB - The quality of premedication induced by oral midazolam and zolpidem, a new imidazopyridine hypnotic, was assessed in a controlled, double-blind study in 93 patients undergoing elective surgery under spinal or extradural anaesthesia. The patients were allocated randomly to three groups. Each group received the same treatment twice at two different doses. The night before operation, patients received zolpidem 10 mg, midazolam 7.5 mg or placebo and, 1 h before operation, zolpidem 20 mg, midazolam 15 mg or placebo. The sleep inducing effects of the drugs were comparable. Zolpidem and midazolam were significantly more effective sedatives than placebo 45 min after administration, but no difference was noted between the drugs. There was a comparable incidence of anterograde amnesia with zolpidem and midazolam, but the onset was shorter after zolpidem. Side effects were comparable in the three groups. Zolpidem is an effective hypnotic with a rapid onset and short duration of action which may be an alternative to midazolam for premedication. PMID- 2198909 TI - Anaesthesia, movement and emesis. AB - One hundred and eighty-two women undergoing dilatation and curettage were allocated randomly to receive premedication comprising temazepam, papaveretum hyoscine or placebo. The temazepam recipients reported significantly fewer episodes of postoperative nausea. Movement was blamed by 66% of patients who identified a cause for nausea. These patients had higher scores on a motion sickness susceptibility questionnaire and were more likely to have been treated previously for nausea or vomiting. It may be possible to identify susceptible patients before surgery. PMID- 2198910 TI - Enhanced Ca2(+)-dependent proteolysis associated with Adriamycin-resistant HL-60 cells. AB - Adriamycin-resistant HL-60 (HL-60/ADR) cells possess high constitutive levels of the proteolytically generated catalytic fragment of protein kinase C, M-kinase, resulting in the generation of pp130 in vitro. In this report, we have demonstrated the presence of a Ca2(+)-activated protease in extracts from HL 60/ADR cells, but not in wild-type cells, which resulted in the generation of 26 and 86 kDa phosphoproteins in vitro, as well as in the reduction of pp130. The formation of pp26 and pp86 and the reduction in pp130 were prevented by the serine/cysteine protease inhibitor, leupeptin. A 26 kDa phosphoprotein with a similar isoelectric point was also evident in both cell lines following metabolic labeling in vivo, although the phosphorylation of pp26 was much greater in resistant cells. These data suggest that the presence of Ca2(+)-dependent protease activity is a phenotypic characteristic of this multidrug resistant cell line. PMID- 2198911 TI - Comparative effects of dilevalol and atenolol on lung function and airway response to methacholine in hypertensive subjects. AB - 1. In this double-blind randomized study, after a 4-weeks placebo period, 18 patients with mild to moderate primary hypertension were assigned to treatment with either dilevalol (n = 9) daily or atenolol (n = 9) over a period of 3 months. 2. Expiratory flows, lung volumes and airway responsiveness (AR) to methacholine were assessed at the end of the placebo period and after an active treatment of 12 weeks. Blood pressure (BP), heart rate (HR) and ECG were monitored during the methacholine challenges. Twice daily peak expiratory flow rates and respiratory symptoms were recorded on a diary card. 3. No significant effects on ECG, HR and BP were observed after methacholine inhalation. In all but one subjects there was no significant change in expiratory flows, lung volumes or AR throughout the study. Mean FEV1, FVC, PEFR, FRC and PC20 methacholine were unchanged after 3 months of treatment, and not statistically different between patients on dilevalol or atenolol. 4. One subject, without previous history of asthma, developed transient airflow obstruction 8 weeks after beginning dilevalol. 5. Dilevalol and atenolol have no significant effects on pulmonary function and AR in most subjects with no baseline airflow limitation. 6. Airflow obstruction may develop in normal subjects on dilevalol. Methacholine challenges are safe in subjects with uncomplicated hypertension. PMID- 2198912 TI - Quinine induces reversible high-tone hearing loss. AB - Serial audiometry was performed in ten patients receiving quinine treatment for acute falciparum malaria. Quinine reduced high tone auditory acuity in all patients, resulting in flattening of the audiograms. The effect was rapid in onset, usually unnoticed (although tinnitus was reported in seven patients), and resolved completely after treatment was completed. PMID- 2198913 TI - War, again. History of the Columbia University School of Nursing 1940-1950. PMID- 2198914 TI - Pediatric nurse practitioners: a view from the founder. Inaugural Jansson lecture. PMID- 2198915 TI - Occupational health education in the United Kingdom workplace: looking backwards and going forwards? The Industrial Health Education Society at work 1922-40. AB - Education on occupational medicine is a neglected area in the United Kingdom in terms of resources and staffing. Education on occupational health and safety is even more neglected and education in the workplace on occupational health is most neglected of all. 1944 saw the demise of the Industrial Health Education Society. This society had been established with the explicit aims of educating and informing ordinary shopfloor workers about occupational hazards and how to deal with them. The emphasis was almost exclusively on occupational health and not occupational safety. In this and indeed in several other respects the society was unique. The society functioned effectively between 1924 and 1940. Large numbers of doctors were recruited to give their time and services free to the IHES by talking to workers on occupational health topics. In this manner the society succeeded in attracting many thousands of workers to its meetings and worked without openly alienating employers, trade unions, the government, or the medical profession--a remarkable feat of diplomacy. The strengths and weaknesses of the society are charted as are the themes and issues still relevant in the 1990s. Progress in the 1980s is assessed against the background of the IHES achievements. PMID- 2198916 TI - Detrusor instability--current management. PMID- 2198917 TI - The efficacy and tolerance of mifepristone and prostaglandin in first trimester termination of pregnancy. UK Multicentre Trial. AB - OBJECTIVE: To investigate the use of oral mifepristone (RU 486) and vaginal gemeprost for the induction of legal first trimester abortion. DESIGN: An uncontrolled multicentre observational study. SETTING: 13 Hospital gynaecological units in Scotland and England. SUBJECTS: 588 Pregnant women with up to nine weeks amenorrhoea having legal abortions. INTERVENTIONS: Oral mifepristone 600 mg followed 48 h later by vaginal gemeprost 1 mg. Women stayed in the hospital for a minimum of 4 h on each occasion. MAIN OUTCOME MEASURES: Frequency of complete abortion and the need for subsequent surgical evacuation, analgesia and blood transfusion. RESULTS: There was complete abortion in 94% (95% CI 92-96%). None of the 46 women at less than 43 days gestation needed surgical evacuation. This was performed in 6.5% of the remainder but among these the rate did not increase with gestation. Five women (four from one centre) required both curettage and blood transfusion. A fall in haemoglobin concentration of 2-4 g/dl occurred in only 1%. Narcotic analgesia was required after gemeprost by 37% of nullipara and 13% of multipara. Overall 26% had vomiting and 13% diarrhoea. CONCLUSION: The sequential use of oral mifepristone and vaginal gemeprost is effective in inducing abortion up to the 63rd day of pregnancy. Efficient management of pain and bleeding is easier if women are in a hospital for some hours after the gemeprost. PMID- 2198919 TI - Thrombin-antithrombin III complex levels in normal pregnancy with hypertensive disorders and after delivery. AB - The plasma concentration of the thrombin-antithrombin III-complex (TAT) was investigated during uncomplicated pregnancy in 15 women in the first, 22 in the second and 46 in the third trimester, and in 19 women with hypertensive disorders between 25 and 40 weeks gestation. Eight women at term after a normal pregnancy were studied before the onset of labour and within 60 min and 24 h after delivery. A comparison group of 16 healthy, non-pregnant women was investigated. The mean TAT concentration in normal pregnancies increased significantly in the second and third trimester compared with values in the first trimester and in non pregnant women. In the group with hypertensive disorders during pregnancy TAT levels were significantly higher than in uncomplicated pregnancies. Within 60 min after delivery a distinct increase of TAT concentrations occurred compared to levels before the onset of labour but the levels had returned to normal by 24 h after delivery. Our findings suggest that an activation of the coagulation system occurs in normal pregnancy. A further activation takes place immediately after delivery. The significantly increased TAT levels in pregnancies with hypertensive disorders suggest a state of chronic disseminated intravascular coagulation leading to an enhanced consumption of and a decreased plasma concentration of antithrombin III. PMID- 2198918 TI - The physiological and clinical effects of progesterone inhibition with mifepristone (RU 486) in the second trimester. AB - A double-blind placebo-controlled trial was performed in 20 primigravidae to assess the physiological and clinical effects of oral mifepristone on myometrial contractility and sensitivity in the second trimester. Ten women received 600 mg of oral mifepristone and 10 women a placebo 24 h before abortion was induced in both groups, with extra-amniotic PGE2 instillation. Intrauterine pressure recordings demonstrated increased spontaneous uterine activity and increased sensitivity to PGE2 and ergometrine, but no change in oxytocin sensitivity after mifepristone treatment. There were no significant differences in PGE or PGF metabolite concentrations in peripheral maternal plasma over the 24-h study period after treatment between the mifepristone and placebo groups. The mean induction abortion interval in the mifepristone group was 512 (SD 321) min compared with 1128 (SD 606) min in the placebo group (P less than or equal to 0.02). The mechanism whereby mifepristone provokes enhanced uterine contractility and sensitivity to prostaglandins, with a reduction in abortion times, does not appear to be through endogenous production of PGE or PGF. PMID- 2198920 TI - Twin pregnancy complicated by single intrauterine death. Problems and outcome with conservative management. AB - During an 11-year period we encountered 16 pregnancies in which one twin died in utero and the pregnancy continued. Eight of these twin pregnancies were monochorionic. None of the women developed severe disseminated intravascular coagulation. The fetal outcome indicates that the prognosis for a surviving dichorionic twin is relatively good, with immaturity the main hazard. By contrast the surviving monochorionic twin has a poor prognosis with a high frequency of neurological damage. This damage is not related to intrapartum or neonatal problems and at present cannot be diagnosed before birth. There is no evidence that birth of the surviving twin by caesarean section will improve the prognosis. Early diagnosis of monochorionic twins and subsequent ultrasound follow up should identify fetal growth discrepancy and possible twin to twin transfusion requiring early delivery. PMID- 2198921 TI - The treatment of detrusor instability in post-menopausal women with oxybutynin chloride: a double blind placebo controlled study. AB - Idiopathic detrusor instability is a common cause of incontinence in the elderly for which anticholinergic agents are regularly prescribed. Oxybutynin chloride combines anticholinergic action with direct muscle relaxant properties. We performed a double blind placebo controlled fixed dose cross over study of oxybutynin chloride in post-menopausal women suffering from detrusor instability. We found oxybutynin chloride significantly more effective than placebo at reducing the symptoms of urgency and urge incontinence and more effective at reducing the height of the highest unstable detrusor contraction. This was at the expense of an increased residual urine and considerable side effects. PMID- 2198922 TI - Successful outcome of pregnancy with severe hypothyroidism. Case report and literature review. PMID- 2198923 TI - Relation between maternal-to-fetal blood glucose gradient and uterine and umbilical Doppler blood flow measurements. PMID- 2198924 TI - Variation in the measurement of fetal abdominal circumference. PMID- 2198925 TI - Listeriosis revisited: the role of the obstetrician. PMID- 2198926 TI - Lyme disease. PMID- 2198927 TI - Ocular Lyme disease: case report and review of the literature. AB - Lyme disease is an emerging new spirochaetal disease in which ocular complications may arise. We have seen a 45-year-old woman who developed unilateral endophthalmitis leading to blindness during the course of this disease. Ocular tissue showed the characteristic spirochete. A literature review shows that the commonest ocular manifestation of Lyme disease is a mild conjunctivitis, but other symptoms may include periorbital oedema, oculomotor palsies, uveitis, papilloedema, papillitis, interstitial keratitis, and others. Ophthalmologists treating patients from Lyme disease endemic areas need to be aware of the protean clinical manifestation of this disease. PMID- 2198929 TI - Anterior segment surgery. PMID- 2198928 TI - Cyclosporin in the treatment of severe chronic idiopathic uveitis. AB - In a randomised double-masked study of 27 patients with a severe chronic idiopathic uveitis we evaluated the efficacy, safety, and tolerability of cyclosporin. All received prednisone in a low dose (0.3 mg/kg/day). In 14 patients this was combined with cyclosporin in a single daily dose of 10 mg/kg/day, while 13 patients received a placebo. The dosages were tapered off in accordance with a protocol, and we compared the number of months of successful therapy before the uveitis relapsed. The efficacy results, as expressed in a Kaplan-Meier curve, were in favour of cyclosporin. Owing to the small sample size, however, this difference did not reach statistical significance. The immunosuppressive effect of cyclosporin was not permanent, and in all but one patient the intraocular inflammation relapsed on reduction of dosage. Rather small cumulative doses of cyclosporin proved to be nephrotoxic, but subjective tolerability for cyclosporin was good. PMID- 2198930 TI - Diabetes and retinal function. PMID- 2198931 TI - A single dose of the topical carbonic anhydrase inhibitor MK-927 decreases IOP in patients. AB - MK-927 is a novel topical carbonic anhydrase inhibitor (CAI). We present the first single-dose clinical trial of MK-927 in 24 patients with bilateral primary open-angle glaucoma or ocular hypertension. This investigation was conducted as a two-centre, double-masked, randomised, placebo controlled study. Patients received one drop of 2% MK-927 in one eye and placebo in the other eye. Modified diurnal intraocular pressure (IOP) curves were performed before the study and on one treatment day. A single dose of 2% MK-927 induced a peak mean IOP decrease of 10.5 mmHg at 4.5 hours postdose. With compensation for diurnal variation, as determined by the prestudy diurnal pressure curve, the net peak mean reduction of IOP caused by MK-927 was 7.5 mmHg versus a corresponding net change of 1.4 mmHg in the contralateral placebo treated eye. Thus a single dose of MK-927 gave a clinically significant IOP reduction in patients. PMID- 2198933 TI - Ocular fluorophotometry. PMID- 2198932 TI - Comparison of the effect of acetazolamide tablets and sustets on diurnal intraocular pressure in patients with chronic simple glaucoma. AB - Twenty patients with primary open-angle glaucoma uncontrolled on single topical therapy completed a double dummy crossover study to compare acetazolamide tablets with a sustained release formulation (Sustet). The two preparations were equally effective, but no direct relationship was found between the intraocular pressure and the plasma concentration of acetazolamide. No difference between the formulations was found in the frequency or severity of side effects. PMID- 2198934 TI - Endogenous Nocardia asteroides endophthalmitis in a patient with systemic lupus erythematosus. AB - We report a case of endogenous Nocardia endophthalmitis in a patient with systemic lupus erythematosus (SLE). He developed a parafoveal lesion in the right fundus while on systemic corticosteroid and antibiotic treatment. Initially we suspected a fungal origin and treated him with antifungal drugs. The intraocular disease progressed without improvement and advanced to the vitreous cavity. Nocardia asteroides was found in a specimen obtained at pars plana vitrectomy and was also cultured from the same specimen. The intraocular infection was controlled by antibacterial drugs, though the visual acuity of the right eye was reduced to only light perception owing to heavy vitreous opacity and secondary cataract. This case is the first report of endogenous Nocardia endophthalmitis in Japan and also the first case of this disease reported from outside the United States of America. PMID- 2198935 TI - The allosteric three-site model for the ribosomal elongation cycle: features and future. AB - The ribosome contains three binding sites for tRNA, viz., the A site for aminoacyl-tRNA (decoding site), the P site for peptidyl-tRNA, and the E site for deacylated tRNA (E for exit). The surprising finding of an allosteric linkage between the E and A sites in the sense of a negative cooperativity has three consequences: (a) it improves the proper selection of aminoacyl-tRNAs while preventing interference from noncognate aminoacyl-tRNAs in the decoding process, (b) it provides an explanation for the ribosomal accuracy without having to resort to the proofreading hypothesis, and (c) it has deepened our understanding of the mode of action of some antibiotics. PMID- 2198936 TI - Site-directed mutagenesis of recombinant rat DNA polymerase beta: involvement of arginine-183 in primer recognition. AB - By site-directed mutagenesis using synthetic oligonucleotides, amino acid residues 181Phe-Arg-Arg183 of recombinant rat DNA polymerase beta were replaced by other amino acids to clarify the roles of these residues in the DNA synthesizing reaction. Replacement of Phe-181 by alanine reduced the enzyme activity only 30%. Replacement of Arg-182 by alanine and glutamine resulted in reduction of the activity by about 67% and 95%, respectively. The Arg-182----Gln replacement increased the binding strength to single-stranded DNA but did not significantly change the Km's for the primer and dTTP, suggesting that Arg-182 is involved in modulation of binding to the template rather than to the primer or deoxyribonucleoside triphosphate. Replacement of Arg-183 by Gln resulted in reduction of the activity by about 95%, and this change, although causing little change in binding strength to single-stranded DNA, resulted in a 3-4-fold increase in the Km's for the primer and deoxyribonucleoside triphosphate. A more dramatic change was observed when Arg-183 was replaced by Ala, which resulted in a 99.98% reduction of enzyme activity. Although the Km for deoxyribonucleoside triphosphate of this mutant enzyme was hardly changed, that for the primer increased 159-fold. Therefore, it is concluded that Arg-183 occupies an important part of the primer recognition site of DNA polymerase beta. PMID- 2198937 TI - DNase I susceptibility of bent DNA and its alteration by ditercalinium and distamycin. AB - The bending of kinetoplast DNA from Crithidia fasciculata is thought to be related to the periodic distribution of AA or TT cluster sequences. The sensitivity to DNase I of the two strands of this DNA was analyzed at nucleotide resolution by sequencing gel electrophoresis. The effect on the DNase I cleavage pattern of two drugs, ditercalinium and distamycin, that are able to remove bending was analyzed. The same analysis was done on a pBR 322 DNA fragment of random sequence as a control. The periodic distribution of the AA or TT clusters in the bent DNA fragment was first analyzed by computing the autocorrelation function of the AA or TT clusters in the bent DNA fragment. It is shown that the AT tracts are on average 10.5 base pairs apart. This value is almost identical with that of the B-DNA helix pitch in solution [10.5 (Wang, 1979); 10.6 +/- 0.1 (Rhodes & Klug, 1980)]. To reveal the periodic pattern of DNase I cleavage on this bent DNA, alone or in presence of drugs, the cross correlation between the different bands obtained from DNAse I cleavage and the presence of AA or TT sequences was computed. This shows that GC and mixed sequences are the most sensitive regions. These data also suggest that there is a periodic fluctuation in the width of the minor groove in the bent fragment. Ditercalinium and distamycin alter the DNase I cutting pattern of the bent DNA fragment but in an inverse fashion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198938 TI - Kinetics of photoinhibition in hydroxylamine-extracted photosystem II membranes: relevance to photoactivation and sites of electron donation. AB - Kinetic analyses were made of the effects of weak-light photoinhibition on the capacity of NH2OH-extracted photosystem II membranes to photooxidize the exogenous electron donors Mn2+, diphenylcarbazide, and I- or to assemble functional water-oxidizing complexes during photoactivation. The loss of capacity for photooxidation of the donors showed two first-order components (half-times of 2-3 min and 1-4 h) with relative amplitudes dependent on the donor, suggesting two photodamageable sites of electron donation (sites 1 and 2, respectively), a conclusion confirmed by analyses of velocity curves of electron donation by each donor. All of the donors appear to be oxidized preferentially by site 1 both at saturating and at limiting light intensity; however, the contribution by site 2 was nearly comparable in saturating light. Loss of photoactivation also exhibited biphasic kinetics, with components having half-times of approximately 0.8 and 3.2 min. The major component (t1/2 = 3.2 min) corresponded to loss of site 1; essentially no photoactivation was observed after its loss. From these and other analyses, we conclude (1) the relative contributions of site 1 and site 2 to the photooxidation of various exogenous electron donors is determined largely by the rates of equilibration of the donors with the two sites, and (2) only site 1 contributes to photoactivation of the water-oxidizing complex. Site 1 is attributed to tyrosine Z of the reaction center's D1 polypeptide. The molecular identity of site 2 is unknown but may be tyrosine D of the D2 polypeptide. PMID- 2198939 TI - Preparation and properties of recombinant DNA derived tobacco mosaic virus coat protein. AB - Recombinant DNA derived tobacco mosaic virus (vulgare strain) coat protein (r TMVP) was obtained by cloning and expression in Escherichia coli and was purified by column chromatography, self-assembly polymerization, and precipitation. SDS PAGE, amino terminal sequencing, and immunoblotting with polyclonal antibodies raised against TMVP confirmed the identify and purity of the recombinant protein. Isoelectric focusing in 8 M urea and fast atom bombardment mass spectrometry demonstrated that the r-TMVP is not acetylated at the amino terminus, unlike the wild-type protein isolated from the tobacco plant derived virus. The characterization of r-TMVP with regard to its self-assembly properties revealed reversible endothermic polymerization as studied by analytical ultracentrifugation, circular dichroism, and electron microscopy. However, the details of the assembly process differed from those of the wild-type protein. At neutral pH, low ionic strength, and 20 degrees C, TMVP forms a 20S two-turn helical rod that acts as a nucleus for further assembly with RNA and additional TMVP to form TMV. Under more acidic conditions, this 20S structure also acts as a nucleus for protein self-assembly to form viruslike RNA-free rods. The r-TMVP that is not acetylated carries an extra positive charge at the amino terminus and does not appear to form the 20S nucleus. Instead, it forms a 28S four-layer structure, which resembles in size and structure the dimer of the bilayer disk formed by the wild-type protein at pH 8.0, high ionic strength, and 20 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2198940 TI - A putative K(+)-selective channel in the plasma membrane of yeast that is blocked by micromolar concentrations of external divalent cations and is insensitive to tetraethylammonium. AB - At pH 7, addition of glucose to an anaerobic suspension of non-metabolizing yeast cells causes a transient net efflux of K+ from the cells and a concomitant transient hyperpolarization of the plasma membrane (Van de Mortel, J.B.J., et al. (1988) Biochem. Biophys. Acta 936, 421-428). Both phenomena are effectively suppressed in the presence of low concentrations of polyvalent cations. The concentrations of Mn2+, Ca2+, Ba2+, Mg2+, Sr2+ and La3+ required for half-maximal suppression of the transient hyperpolarization are 10, 17, 20, 38, 47 and 5 microM, respectively. Subsequent addition of EDTA 90 s after that of Ca2+ immediately restores both K+ efflux and cellular uptake of the fluorescent membrane potential probe 2-(dimethylaminostyryl)-1-ethylpyridinium (DMP). This suggests that an interaction of polyvalent cations with an external binding site blocks the putative K(+)-selective channel. Opening of this channel is not blocked by 20 mM tetraethylammonium nor by 100 microM 3,4-diaminopyridine. It is argued that this glucose-induced K(+)-conductive pathway is not identical to the voltage-gated K+ channels identified until now in patch-clamp studies of the yeast plasma membrane. PMID- 2198941 TI - The role of carbohydrate in the function of human plasminogen: comparison of the protein obtained from molecular cloning and expression in Escherichia coli and COS cells. AB - A cDNA library was constructed in the phage lambda gt11 from human liver mRNA enriched for plasminogen mRNA by chromatography on Sepharose 4B. A full-length cDNA clone of human plasminogen was isolated. The 2.7 kb cDNA encoded the entire plasminogen molecule, a signal peptide sequence and two start codons with a 5' untranslated region of about 80 base pairs. In the 3'-non coding region of 280 base pairs a consensus signal AATAAA was found at a distance of 46 base pairs upstream of the poly(A) tail. The plasminogen cDNA was subcloned in the eukaryotic expression vector p91023 (B), and human plasminogen was expressed in monkey kidney (COS m6) cells and in Escherichia coli. The recombinant molecule obtained from COS cells has physicochemical and biological properties similar to native human plasminogen I, indicating that it has folded in a manner similar to plasminogen synthesized by liver. By contrast, plasminogen expressed in E. coli could not be activated and showed biological properties which are very different from glycosylated forms of plasminogen. However, the non-glycosylated plasminogen was bound by lysine-Sepharose and reacted with a conformation dependent monoclonal antibody to kringles 1 to 3. These data suggest that the protein has properly folded kringle domains. Our studies suggest that the carbohydrate domains may play an important role in the function of the plasminogen molecule. PMID- 2198942 TI - Amino acid sequences of the ribosomal proteins HL30 and HmaL5 from the archaebacterium Halobacterium marismortui. AB - The complete amino acid sequences of the ribosomal proteins HL30 and HmaL5 from the archaebacterium Halobacterium marismortui were determined. Protein HL30 was found to be acetylated at its N-terminal amino acid and shows homology to the eukaryotic ribosomal proteins YL34 from yeast and RL31 from rat. Protein HmaL5 was homologous to the protein L5 from Escherichia coli and Bacillus stearothermophilus as well as to YL16 from yeast. HmaL5 shows more similarities to its eukaryotic counterpart than to eubacterial ones. PMID- 2198943 TI - Structural studies on the subunits of glutamate synthase from Azospirillum brasilense. AB - The amino acid composition and the N-terminal sequences of the two dissimilar subunits of glutamate synthase from Azospirillum brasilense have been determined along with the sequences of selected CNBr peptides. Comparison of our data with those available for Escherichia coli glutamate synthase revealed an overall good homology between the enzymes from the two sources. This is more evident for the heavy subunits where the highly conserved N-terminal sequence containing Cys-1, suggests that this region may be involved in catalysis. However, it appears that the light subunits are different with respect to both their amino acid composition and their N-terminal region, suggesting that the latter may not be part of the enzyme active site. Finally, an extinction coefficient at 444 nm of 62.66 +/- 4.61 mM-1.cm-1 was determined. PMID- 2198944 TI - Bifunctional antibodies: concept, production and applications. AB - Immunoglobulins, or antibodies, are monospecific, bivalent antigen-binding molecules. Bifunctional antibodies are bispecific, with each arm binding to a different antigen, and may be produced by biological or chemical methods. Biological production involves the fusion of two monoclonal antibody-producing hybridomas or of an immunised spleen cell and a hybridoma. The resulting hybrid hybridomas (quadromas or triomas) secrete a mixture of parenteral monoclonal antibodies and bifunctional antibody. In chemical production, the parental monoclonal antibodies can be 'chopped up and reconstituted' to produce the bifunctional antibody only. Bifunctional antibodies have a variety of potential uses. They were originally proposed as an aid to cancer chemotherapy where one of the arms of the antibody would bind to a tumour marker and the other to a drug, toxin, or cytotoxic cell. Functional agents can thus be target directly onto tumour cells, accumulating with higher density, yet with reduced side effects for the patient. Further applications have been proposed involving enzyme immobilization and novel immunoassay techniques. This review describes developments that have taken place in bifunctional antibody technology to date. PMID- 2198945 TI - Reactive sulfhydryl groups in Saccharomyces cerevisiae phosphoenolpyruvate carboxykinase. AB - Saccharomyces cerevisiae phosphoenolpyruvate carboxykinase (ATP:oxaloacetate carboxy-lyase (transphosphorylating), EC 4.1.1.49) is inactivated by several thiol- and vicinal dithiol-specific reagents. Titration experiments of the enzyme with 5,5'-dithiobis(2-nitrobenzoate) (DTNB) show the presence of reactive monothiol and vicinal dithiol groups, whose modifications lead to enzyme inactivation. The enzyme is also inactivated by N-(1-pyrenyl)iodoacetamide (PyrIAM), with a binding stoichiometry of approx. 2 mol per mol of enzyme subunit. A high level of pyrene excimer fluorescence is detected on the labeled enzyme, thus implying the reaction of the reagent with two spatially close sulfhydryl groups in the protein. The carboxykinase is not completely inactivated by different vicinal dithiol-specific reagents, thus implying a catalytically non essential character for these groups. From substrate protection experiments of the enzyme inactivation by DTNB, PyrIAM and vicinal dithiol-specific reagents, it is concluded that the loss of enzyme activity is caused by the modification of both thiol and vicinal dithiol groups in the substrate binding region. PMID- 2198946 TI - Non-sterol structural probes of the lanosterol 14 alpha-demethylase from Saccharomyces cerevisiae. AB - A number of non-sterol iron-liganding molecules were used to probe the active site of the lanosterol 14 alpha-demethylase from Saccharomyces cerevisiae. Simple bi- and tricyclic aromatic amines were found to exhibit Type II binding spectra with the demethylase. Stereochemical and positional effects appear to play critical roles in the binding of these compounds to the demethylase. These compounds have been used to generate additional active-site structural information on this enzyme, currently a target for the development of new antifungal agents. PMID- 2198947 TI - Phosphatidylethanolamine methyltransferase and phospholipid methyltransferase activities from Saccharomyces cerevisiae. Enzymological and kinetic properties. AB - In the yeast Saccharomyces cerevisiae, two membrane-associated enzymes catalyze the three-step methylation of phosphatidylethanolamine (PE) to phosphatidylcholine (PC). Phosphatidylethanolamine methyltransferase (PEMT) catalyzes the first methylation reactions (PE--- phosphatidylmonomethylethanolamine (PMME] and phospholipid methyltransferase (PLMT) catalyzes the second two methylation reactions (PMME--- phosphatidyldimethylethanolamine (PDME)----PC). Using gene disruption mutants of the S. cerevisiae OP13 and CHO2 genes, we independently studied the enzymological properties of microsome-associated PEMT and PLMT, respectively. The enzymological properties of the enzymes differed with respect to their pH optima, cofactor requirements and thermal lability. For the PEMT reactions, the apparent Km values for PE and S-Adenosylmethionine (AdoMet) were 57 microM and 110 microM, respectively. For the PLMT reactions, the apparent Km values for PMME and PDME were 380 microM and 180 microM, respectively. The apparent Km values for AdoMet were 54 microM and 59 microM with PMME and PDME as substrates, respectively. S Adenosylhomocysteine (AdoHcy) was a competitive inhibitor of PEMT (Ki = 12 microM) and PLMT (Ki = 57 microM and Ki = 54 microM for PMME and PDME, respectively) with respect to AdoMet. AdoHcy was a noncompetitive inhibitor of PEMT (Ki = 160 microM) and PLMT (Ki = 120 microM) with respect to PE and PMME and PDME, respectively. PMID- 2198948 TI - [Complexes of phorbol tumor promoters with protein kinase C]. AB - Based on the literature data, a systematic comparison of relationships between the structures of incomplete and complete phorbol tumor promoters, diacylglycerols and their activities in various biological test-systems was carried out. The specific features of the phorbol esters-protein kinase C complexes responsible for the induction of the first and second stages of the tumor promotion in mouse skin, were established. The type of diacylglycerol binding to protein kinase C which confers to the latter noncarcinogenic properties, was specified. PMID- 2198949 TI - [The effect of various forms of thrombin on nonspecific high molecular weight substrates]. AB - The ability of native alpha- and non-coagulating gamma-thrombin to catalyze the hydrolysis of nonspecific high molecular weight substrates was studied using chymotrypsinogen and the oxidized insulin B-chain as substrates. The effect of thrombin on chymotrypsinogen was estimated by the appearance of caseinolytic activity measured by the increase in the number of terminal NH2-groups in the 2,4,6-trinitrobenzol sulfonic acid reaction. The same reaction was used to study the hydrolysis of insulin by thrombin. It was found that the destruction of the additional center necessary for fibrinogen proteolysis during the alpha-thrombin conversion to the gamma-form did not affect the enzyme ability to hydrolyze nonspecific protein substrates. It was assumed that the low efficiency of non physiological high molecular weight substrate hydrolysis by thrombin is due to the lack of specific remote interactions in the regulatory site outside the enzyme active center. PMID- 2198950 TI - [Kinetics of L-gamma-Glu-pNA hydrolysis by destabilase, the enzyme from the medicinal leech Hirudo medicinalis]. AB - The molecular mass of destabilase isolated from the medicinae leech Hirudo medicinalis was found to be equal to 12.3 kDa. A kinetic analysis of the sole presently known synthetic substrate, L-gamma-Glu-pNA, showed that the enzyme is relatively stable to heating (5 min, 70 degrees C); the pH optimum lies at 7.0 8.5. The enzyme has a specific activity of 0.15 x 10(-9) mol.s-1.mg-1; Km = 2.2 x 10(-4) M, kcat is 3.53 x 10(-3) s-1 (pH 8.0, 37 degrees C). PMID- 2198951 TI - Asymmetric metabolism over basal ganglia in catatonia. PMID- 2198952 TI - Comorbidity in the interpretation of dexamethasone suppression test results in children: a review and report. AB - The dexamethasone suppression test (DST) was administered as part of the initial clinical assessment to 83 children and adolescents who were consecutively referred for outpatient evaluation. All diagnoses were made clinically by a child psychiatrist according to DSM-III criteria. A weight-corrected dose of dexamethasone of 17 micrograms/kg was used. DSM-III diagnoses were made independent of DST results. Patients were stratified into four main diagnostic groups: major depressive disorder (MDD) (N = 27); attention deficit disorder with hyperactivity (ADDH) (N = 22); major depressive disorder plus attention deficit disorder with hyperactivity (MDD + ADDH) (N = 29); and psychiatric controls (PC) (N = 5). Rates of dexamethasone nonsuppression were found to be similarly elevated in children with MDD (29.6%), ADDH (22.7%), and MDD + ADDH (37.9%). All 5 psychiatric control patients had a normal postdexamethasone suppression (0%). A similar pattern of results emerged in a reexamination of the literature on available studies of DST in juveniles which revealed that children with major affective disorders, attention deficit disorder (ADDH), and anxiety disorders had comparable DST results that were significantly higher than the 5.6% rate found in normal controls. These findings provide further support for similarities in DST results between ADDH and MDD in outpatients. Although these results suggest a lack of specificity of the DST as a laboratory aid for the diagnosis of juvenile affective disorders, they are also consistent with findings indicating that the DST may be an index of clinical severity and other findings suggesting a possible association between ADDH and MDD. Despite its limitations, the DST may provide potentially useful clinical and research information regarding the pathophysiology of psychiatric disorders and in alerting clinicians to the presence of serious psychiatric disorders. The findings also stress the relevance of assessing comorbidity in interpreting DST results. PMID- 2198953 TI - Pituitary responsiveness to luteinizing hormone-releasing hormone in prepubertal and postpubertal male ferrets. AB - The pituitary response to three different doses of exogenously administered LHRH was examined in prepubertal (9-wk-old) and postpubertal (32-wk-old) male ferrets. The doses of 5, 10, and 15 ng LHRH/kg body weight tested in this study produced dose-related increases in circulating LH concentrations in both pre- and postpubertal groups. In addition, a significant effect of age on LH response was observed, with the prepubertal animals demonstrating significantly greater serum LH values in response to the two higher doses than the postpubertal males. Prepubertal ferrets also exhibited a significant increase in endogenous LH pulse amplitude in sampling periods following exogenous administration of LHRH compared to baseline pulse amplitudes in periods prior to the LHRH infusions. These results suggest that the low frequency of endogenous LH pulses previously observed in prepubertal ferrets is not due to unresponsiveness of the pituitary gland to LHRH. Thus, suppression of the hypothalamo-hypophyseal axis observed in the prepubertal ferret is probably mediated at the level of the hypothalamus. PMID- 2198954 TI - Localization of oviductal glycoproteins within the zona pellucida and perivitelline space of ovulated ova and early embryos in baboons (Papio anubis). AB - The estrogen-dominated baboon oviductal epithelium synthesizes and secretes a family of oviduct-specific glycoproteins. The objective of this study was to determine if these glycoproteins become associated with ova and early embryos. Ovarian and oviductal eggs obtained from superovulated baboons 72 h post-hCG were subjected to an indirect immunofluorescent assay that used a polyclonal antibody prepared toward the baboon oviduct-specific glycoproteins. Oviductal ova as well as 2-cell and 4-cell embryos showed intense, specific fluorescence within their zonae pellucidae. Ovarian ova did not exhibit fluorescence. Oviductal eggs were also fixed and processed for peroxidase-antiperoxidase immunocytochemistry and colloidal gold immunoelectron microscopy to confirm the immunofluorescent data and to determine the subcellular distribution of the antigens. Oviductal ova as well as 2-cell and 3-cell embryos exhibited immunolabeling localized within the zona. Gold particles were distributed uniformly throughout the width of the zona. Occasional groupings of gold particles were observed within the zona. Also, in most eggs, immunoreactivity was observed associated with flocculent material in the perivitelline space as well as the vitelline membrane. Furthermore, immunogold labeling above background level was noted in the cytoplasm of the eggs, particularly in the blastomeres of 3-cell embryos. Collectively, these results indicate that baboon estrogen-dependent oviductal secretory glycoproteins become intimately associated with oviductal ova and with embryos. PMID- 2198955 TI - [Induction by corticosteroids of systemic candidiasis in adult mice infected during the neonatal period]. PMID- 2198956 TI - Treatment of Cooley's anemia. PMID- 2198957 TI - Subcutaneous recombinant granulocyte-macrophage colony-stimulating factor used as a single agent and in an alternating regimen with azidothymidine in leukopenic patients with severe human immunodeficiency virus infection. AB - We investigated the effects of recombinant human granulocyte-macrophage colony stimulating factor (rGM-CSF) administered by the subcutaneous route, first alone and then alternating with azidothymidine (AZT), in leukopenic patients with severe human immunodeficiency virus (HIV) infection. Ten patients with acquired immunodeficiency syndrome (AIDS) or related disorders, five of whom could not tolerate conventional doses of AZT, were administered rGM-CSF subcutaneously for 12 days. They then were administered an alternating regimen using AZT for 1 week, followed by 5 days of subcutaneous rGM-CSF and 2 days without any medication. During the initial 12 days of GM-CSF administration, there was an increase in the mean white blood cell (WBC) value. In addition, rGM-CSF stimulated circulating monocytes as evidenced by an increase in superoxide anion production and expression of surface HLA-DR antigen. However, at the same time rGM-CSF increased the serum HIV p24 antigen in each of the six evaluable patients from 189 x/divided by 2.02 pg/mL (geometric mean x/divided by SEM) at entry to 375 x/divided by 2.11 pg/mL (P less than .05). During the subsequent period of alternating AZT and rGM-CSF treatment, serum HIV p24 antigen fell below the day 14 value in most patients, particularly after the weeks of AZT administration. The mean T4 cell value increased in patients who had not previously received AZT, but generally did not change in those who had prior AZT exposure. Hematologic toxicity appeared to be somewhat reduced compared with continuous full-dose AZT therapy, and two patients with previous AZT hematologic toxicity tolerated this alternating regimen for 25 weeks. Additional regimens simultaneously combining these two agents are worth exploring. PMID- 2198958 TI - Detection of the target progenitor cells of granulomonopoietic enhancing activity. AB - Macrophage-derived granulomonopoietic enhancing activity (GM-EA) is a novel mediator that amplifies colony formation of myeloid progenitor cells (CFU-GM) in conjunction with colony-stimulating factors (CSFs), and is distinct from other hematopoietic synergizing factors such as interleukin (IL)-1, IL-4, and IL-6. In the present study, we try to ascertain whether or not there is a GM-EA-specific responsive myeloid progenitor cell population. Human bone marrow cells deleted of adherent cells and T lymphocytes were separated by velocity sedimentation into three subpopulations with respective sedimentation rates (millimeters per hour) of 7.4 +/- 0.4, 6.0 +/- 0.6, and 4.7 +/- 0.3. These subpopulations corresponded to the day 7 CFU-GM, day 14 CFU-GM, and the earlier myeloid progenitor cells, pre CFU-GM, respectively. Pre-CFU-GM failed to respond to the colony-inducing effect of GM-CSF but could be stimulated by GM-EA alone to generate small clusters (5 to 25 cells) in soft agar after 14 days of incubation. Correspondingly, suspension preculture of the fractionated bone marrow cells also showed that only the progenitor cells with low sedimentation rate (4.7 mm/h) could be activated by GM EA to generate CFU-GM. Taken together, our results suggest that the specific target cell of GM-EA is the pre-CFU-GM, and that GM-EA acts on these cells as a growth/maturation factor, but on the day 7 and day 14 CFU-GM as a synergistic growth factor. PMID- 2198959 TI - A new hematopoietic cell line, KMT-2, having human interleukin-3 receptors. AB - A novel human cell line, KMT-2, from umbilical cord blood cells was established based on the selection of cultures in the presence of recombinant human interleukin-3 (IL-3) and the sorting of cells with anti-My 10 antibody. Morphologic and cytochemical studies (peroxidase negative, Sudan-black negative, chloroacetate esterase negative, PAS positive, nonspecific esterase positive) and phenotyping (HLA-DR, My7 = CD13, My9 = CD33, My10 = CD34, MCS-2, LeuM1 positive, glycophorin A negative, and P2 negative) suggest that the KMT-2 cells are myelomonocytic cells, probably of immature progenitor origin. Besides IL-3, granulocyte-macrophage colony-stimulating factor supported the growth of the KMT 2 cells, but IL-1 alpha, IL-2, IL-4, IL-5, and erythropoietin did not. IL-6 showed only slight activity. Binding studies with 125I-labeled recombinant human (rh) IL-3 indicated that IL-3 bound to a single class of high affinity receptors (approximately 4,000 receptors/cell) on KMT-2 cells with a kd of approximately 200 pmol/L. The chemical cross-linking assay demonstrated that radiolabeled hIL-3 bound three molecules with molecular masses of 170, 130, and 70 Kd. Present data suggest that the newly established human cell line will be a valuable tool for the biologic assay of hIL-3, and a model for biochemical studies of IL-3 receptors. PMID- 2198960 TI - Cytokine regulation of the human burst-forming unit-megakaryocyte. AB - The human burst-forming unit-megakaryocyte (BFU-MK) is a primitive megakaryocytic progenitor cell. A marrow cell population enriched for BFU-MK (CD34+ DR-) was obtained by monoclonal antibody labeling and fluorescence-activated cell sorting. CD34+DR- cells were assayed in a serum-depleted, fibrin clot culture system. Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF), recombinant interleukin-3 (rIL-3), and megakaryocyte colony-stimulating factor (MK-CSF), partially purified from human plasma, were each individually capable of promoting BFU-MK-derived colony formation. Recombinant erythropoietin, rG-CSF, rIL-4, rIL-6, and thrombocytopiesis stimulating factor, partially purified from human embryonic kidney cell conditioned media, had no stimulatory effect on BFU MK-derived colony formation when added alone or in various combinations with either GM-CSF, IL-3, or MK-CSF, GM-CSF and IL-3, GM-CSF and MK-CSF, but not IL-3 and MK-CSF had additive actions in promoting BFU-MK-derived colony formation, rIL 1 alpha had no influence alone on BFU-MK cloning efficiency, but had a dose dependent, synergistic effect with IL-3, but not with GM-CSF or MK-CSF. The synergistic relationship between IL-1 alpha and IL-3 was abrogated by addition of an IL-1 alpha neutralizing antibody but not by a GM-CSF neutralizing antiserum, suggesting that IL-1 alpha acts directly on the BFU-MK and not by stimulating marrow auxiliary cells to secondarily release additional cytokines. Information presented here indicates that the regulatory influence, acting on the different stages of megakaryocyte development, are stage-specific and accomplished by multiple cytokines. PMID- 2198961 TI - Establishment and characterization of a granulocyte-macrophage colony-stimulating factor-dependent human myeloid cell line. AB - A new human myeloid cell line has been established recently from the bone marrow cells of a patient with chronic myelogenous leukemia in blast crisis. The active proliferation and survival of the cells in RPMI 1640 medium containing fetal calf serum are clearly dependent on the presence of either natural or recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Despite permanent culturing in rhGM-CSF (100 U/mL), the cells do not differentiate and bear the myelomonocytic surface markers CD34, CD13, CD36, as well as HLA-DR, but not CD3, CD7, CD10, CD11b, CD14, CD20, or CD42b. The predominant karyotype, apart from tetraploidy in several cells, is 45, XX, -9, -17, -19, -22, 7p-, 9q+ (der t[9;22]), der (13q), with three additional marker chromosomes, from which one was observed in the patient's leukemic cells. On BglII-digested DNA, Southern blot analysis with bcr 5' as the probe detected two additional hybridizing restriction fragments of 8.6 and 11.0 kilobase pairs. PMID- 2198962 TI - Chromosomal breakpoints within the first intron of the ABL gene are nonrandom in patients with chronic myelogenous leukemia. AB - Bone marrow cells from 37 patients with chronic myelogenous leukemia (CML), who had the characteristic Philadelphia chromosome in their leukemic cells, were examined for ABL gene rearrangement by pulsed-field gel electrophoresis. By using several probes from the ABL gene, we found that in 33 of 37 (89%) patients studied, the translocation breakpoints in ABL fell within the 175-kilobase (kb) intron between exons 1b and 1a. Furthermore, breakpoints in this intron clustered in three regions, approximately 30 +/- 5, 100 +/- 13, and 135 +/- 8 kb downstream from exon 1b. These findings suggest that there may be specific sequences in this intron that facilitate the processes of chromosomal translocation. PMID- 2198964 TI - Human immunodeficiency virus DNA amplification and serology in blood donors. AB - The significance of indeterminate screening antibody test for human immunodeficiency virus (HIV) serology is still difficult to evaluate, especially in low-risk populations. One hundred twenty-seven blood donors with an initially reactive screening test for HIV antibodies were enrolled in this study. The sera of 95 of these blood donors were reactive on repetition of the test, and none had detectable circulating p24 antigen. Western blot (WB) analysis of the repeatedly reactive sera was as follows: 9 positive, 31 indeterminate, and 55 negative. One of the blood donors with indeterminate WB later presented a seroconversion. On subsequent control 3 to 12 months later, the sera from donors with indeterminate or negative WB did not present any parameters that may indicate a seroconversion. DNA was purified from citrated blood collected from the 127 blood donors at the time of the initial antibody screening. Five micrograms of each DNA sample corresponding to 7 x 10(5) nucleated white blood cells was amplified by polymerase chain reaction (PCR) in the presence of oligonucleotides (primers) corresponding to a highly conserved segment of the pol gene. The detection of amplified DNA was achieved by dot blot and Southern blot using appropriate 32P labeled oligonucleotides. Ten DNA samples were positive, 9 corresponded to blood donors with a positive HIV serology, and 1 to the blood donor who later presented a seroconversion. These results confirm the sensitivity of the PCR for the diagnosis of HIV infection; they also suggest that repetition of the serology at 3- to 12-month intervals is a valuable procedure for the control of HIV infection status in blood donors. PMID- 2198963 TI - An antibody that facilitates hematopoietic engraftment recognizes CD44. AB - Pretreatment of recipients with the monoclonal antibody (MoAb) S5 facilitates engraftment of bone marrow from mismatched, unrelated donors in the canine transplantation model. In the direct comparisons reported here, the S5 glycoprotein (gp) was found to have structural homology to CD44 that in humans has been implicated in adhesive interactions of one type of effector cell, the lymphocyte. The S5 antigen and gp90Hermes-1 exhibited codistribution on canine peripheral blood cells. Both S5 and Hermes-1 (anti-CD44) MoAbs recognized 90-Kd species in radioimmune precipitations of 125I surface-labeled canine peripheral blood lymphocytes and bone marrow cells. Competitive antibody binding experiments showed that the epitope detected by S5 was distinct from that bound by Hermes-1 but overlapped with those defined by two other known anti-CD44 reagents, IM7 and Hutch-1. Sequential immunoprecipitation with S5 and Hermes-1 indicated that the two antibodies recognize the same or overlapping subsets of membrane gps. Tryptic digestion of S5 and anti-CD44 immunoprecipitates generated two major iodinated peptides of 27 and 35 Kd in both cases, a further indication of structural homology. Similarly, after N-glycanase digestion, S5 and CD44 immunoprecipitates were resolved to a single 68-Kd species. These findings suggest that CD44 mediated adhesive events may affect the fate of transplanted hematopoietic cells. The previous implications of this gp in T-lymphocyte activation and lymphocyte adhesion to endothelium thus provide useful paradigms to analyze its function in the bone marrow transplant setting. PMID- 2198965 TI - The tobacco use research program at Oregon Research Institute. AB - The research program at ORI deals with both adolescent and adult tobacco use and is guided by a behavioral framework which emphasizes the role of the social context in tobacco use onset, maintenance and cessation. Growing appreciation of the importance of social context variables, combined with an emerging recognition of the need for a public health rather than clinical perspective on tobacco use, have led to a focus on interventions in larger social systems such as schools, worksites, health care plans, and communities. This research requires attention to the science of behavior change at both the individual and organizational levels. PMID- 2198966 TI - Conditioned learning in alcohol dependence: implications for cue exposure treatment. AB - A review of the literature pertinent to cue exposure treatment in alcohol dependence is presented. Psychological models of relapse, based on conditioning and social learning theories, are critically evaluated. In particular, attention is drawn to the potential implications for cue exposure research and treatment of an interaction between Pavlovian and operant conditioning, problems with the application of the concepts of arousal and craving and the importance of a systems model to understand physiological responses. It is concluded that no study has so far demonstrated a link between conditioned responses to alcohol related cues and relapse, an assumption on which cue exposure treatment is based. Further, the evidence for the effectiveness of cue exposure as a treatment is lacking. Promising research directions are identified. PMID- 2198967 TI - Rapid viral diagnosis in perspective. PMID- 2198968 TI - The natural course of myasthenia gravis. PMID- 2198969 TI - Desensitisation today. PMID- 2198970 TI - Experiences of a battalion medical officer in the retreat to Dunkirk: V. PMID- 2198971 TI - ABC of major trauma. Management of hypovolaemic shock. PMID- 2198972 TI - The expected fraction of clonable genomic DNA. AB - Random clone mapping of genomic DNA is a subject of great interest in molecular biology. E. coli has just been mapped and work is progressing on some human chromosomes. In this paper we give estimates of the fraction of genomic DNA which is not clonable by partial digest with a restriction enzyme. PMID- 2198973 TI - Detection of Salmonella typhi carriers in food handlers by Vi serology in Lima, Peru. AB - The work described here sought to assess the merits of using an indirect hemagglutination test employing highly purified Vi antigen to screen a high-risk population for chronic S. typhi carriers in Lima, Peru. A total of 1,931 female food handlers over 30 years old were enrolled in the study. Indirect hemagglutination tests performed on these subjects' sera, taking a titer of 1:40 or more as positive, yielded 29 positive results. Subsequent bacteriologic testing performed on 26 of these 29 subjects identified four (15%) as S. typhi carriers. The procedure had a sensitivity of 79%, indicating that the prevalence of S. typhi carriers among the population studied was on the order of 262 per 100,000. It appears that Vi serology employing highly purified Vi antigen offers a practical and cost-effective way of screening for S. typhi carriers in both endemic and nonendemic typhoid fever areas. PMID- 2198974 TI - The rationale for controlling dietary lipids in the prevention of coronary heart disease. AB - Despite the acknowledged association between blood cholesterol levels and coronary heart disease, many people throughout the Americas remain uncertain about the importance of that association and available countermeasures. This article reviews the subject's historical background, results of recent studies, and current recommendations of leading expert groups in the United States. It also examines ways in which the body's cholesterol level is influenced by changes in the dietary intake of calories, saturated and unsaturated fats, and cholesterol, and recommends the adoption of specific dietary measures as a way of markedly improving public health. PMID- 2198975 TI - Local formation of angiotensin II in the rat aorta: effect of endothelium. AB - 1. The local formation of angiotensin II (AII) from its precursors, angiotensin I (AI) and tetradecapeptide (TDP) renin substrate, was studied in intact (with endothelium) and rubbed (without endothelium) aortic rings of the rat. 2. AI and TDP renin substrate maximally contracted intact tissues in a similar way to AII. The same observations were made in rubbed tissues. 3. The maximal response and the sensitivity of the aorta to these agonists were greater in rubbed than in intact tissues. 4. In intact preparations, methylene blue increased the contractile response to AII and TDP to the same extent as endothelium removal. 5. In intact preparations, AII receptor blockade completely suppressed all contractile responses, converting enzyme inhibition completely blocked the responses to AI and TDP, and renin inhibition partially blocked the responses to TDP. 6. In rubbed preparations, AII receptor blockade completely inhibited all contractile responses, converting enzyme inhibition completely suppressed the responses to AI but only partially inhibited those to TDP, and renin inhibition partially blocked the responses to TDP. 7. In conclusion, the formation of AII from TDP and its blockade by a converting enzyme inhibitor and a renin inhibitor shows that converting enzyme and a renin-like aspartic proteinase are present in the aortic wall. Furthermore, the results show that the endothelium is not essential for the conversion of the TDP to AII, but modulates the responses to locally formed AII through the release of endothelium-derived relaxing factor (EDRF). PMID- 2198976 TI - Immunohistological reassessment of accessory cell populations in normal and diseased human synovium. AB - Accessory cell populations in normal and diseased synovial tissue have been reanalyzed following the development of the monoclonal antibody, EBM11, directed against the CD68 epitope which is expressed by macrophages in all locations so far examined. Previous studies used as a macrophage marker the monoclonal antibody RFD7 which binds only a proportion of (mature) macrophages. Using double indirect immunofluorescence, normal and rheumatoid synovial samples were examined for the presence of cells which bind the putative dendritic cell marker, RFD1, in conjunction with either RFD7 or EBM11. RFD1 positive cells were found in five of 40 normal synovia. Of these cells, 30-35% were negative for RFD7 or EBM11 and, when closely apposed to T-lymphocytes, showed a typical interdigitating morphology. In contrast, all of ten rheumatoid synovia contained RFD1 positive cells; the extent of double labelling with macrophage markers varied with the position of the cells in the tissue. As expected, EBM11 stained a larger number of cells with macrophage morphology than RFD7. The combination of RFD1 and EBM11 appears to be a useful method for identifying interdigitating dendritic cells in connective tissue, these cells being characterized by positive RFD1 and negative EBM11 binding. On this criterion, interdigitating dendritic cells were plentiful in rheumatoid synovium and present, albeit infrequently, in normal synovium. PMID- 2198978 TI - Review of UK data on the rheumatic diseases--2. Rheumatoid arthritis. PMID- 2198977 TI - Intramuscular depot methylprednisolone induction of chrysotherapy in rheumatoid arthritis: a 24-week randomized controlled trial. AB - Fifty-nine patients commencing intramuscular sodium aurothiomalate therapy were randomized to receive three doses of 120 mg intramuscular depot methylprednisolone acetate or matching placebo at weeks 0, 4, and 8 in addition to chrysotherapy. The group receiving methylprednisolone had more rapid disease improvement. This advantage persisted for up to 12 weeks, although by 24 weeks both groups exhibited similar benefits due to continued improvement in the group treated with gold alone. Withdrawals secondary to gold-induced side-effects occurred later in the steroid group (median time to withdrawal: 15 weeks steroid; 4.5 weeks placebo, P less than 0.05), and there were fewer withdrawals due to a lack of effect in the steroid group (one steroid versus three placebo, P NS). We conclude that glucocorticoids given as intermittent, intramuscular depot injections have a significant short term benefit which can be maintained by concomitant administration of intramuscular gold. PMID- 2198979 TI - Thyroid imaging using positron emission tomography--a comparison with ultrasound imaging and conventional scintigraphy in thyrotoxicosis. AB - Forty-six comparative studies were performed on 41 patients with hyperthyroidism. Clinically these comprised two groups: those with Graves' disease, and those with multinodular goitre. All patients underwent an ultrasound examination and positron emission tomography (PET) using 124I, then gamma camera pinhole imaging following their 131I therapy administration. Although the 131I pinhole imaging was not performed for diagnostic purposes, there was good correlation (78% agreement) between it and 124I PET in determining relative lobe size. Hence either imaging modality could be used as an indicator of the relative radiation dose delivered to each thyroid lobe at a macroscopic level. In terms of gland morphology the PET images corresponded well to the high resolution ultrasound images (78% agreement), unlike the pinhole images which correlated poorly (only 28% agreement). The results showed that PET imaging gives better anatomical and physiological detail than 131I pinhole imaging. In 77% of cases where the pinhole image showed a uniform distribution of radioisotope, the improved spatial resolution of the PET images revealed non-homogeneous distribution indicating a non-uniform distribution of radiation dose. Since all dosimetry calculations are based on the assumption of uniform distribution of radioiodine, this non uniformity could possibly have important consequences in the outcome of radioiodine therapy in thyrotoxicosis. PMID- 2198980 TI - The ultrasound cystodynamogram--a new radiological technique. AB - Voiding dysfunction may be assessed using the intravenous urodynamogram (IVUD) or combined with pressure studies in the videocystometrogram (VCMG). However, VCMG requires bladder catheterization and voiding in public which often leads to inhibition of sphincter relaxation. For this reason the urinary flow rate measurement performed in private is more representative of the true voiding pattern. The ultrasound cystodynamogram (USCD) evaluates the bladder capacity, mean and maximum flow rates, flow pattern and post-micturition residual. The diagnostic capability of USCD was studied in 116 consecutive cases 46 of whom had also had VCMG. Comparison of the data obtained using both techniques revealed no significant difference. USCD has proved to be accurate, safe and reproducible and is of particular value in patient follow-up. PMID- 2198981 TI - Congenital biliary dilatation: a spectrum of disease detailed by ultrasound. AB - Recently we have examined six children with the diagnosis of choledochal cyst who demonstrate a greater spectrum of biliary involvement than expected. Classically choledochal cysts have been divided into types and subtypes based on the configuration of common bile duct dilatation; however, this simplified information is misleading since surgical management is dependent on the exact extent of intrahepatic and extrahepatic biliary abnormalities. The pre-operative ultrasound examination must be meticulous to provide enough pertinent anatomic details. Much of the intrahepatic anatomy is not visualized at surgery nor on the operative cholangiograms where reflux of contrast into the intrahepatic ducts may not be consistently achieved. PMID- 2198982 TI - The effect of Captopril on benign and malignant reactions in irradiated rat skin. AB - The effect of the angiotensin converting enzyme inhibitor Captopril on the severity of radiation-induced epilation and moist desquamation and the incidence of skin tumours was determined for up to 52 weeks in male rats. The irradiation consisted of a range of single doses (0, 10, 20, 30 Gy) of 60Co gamma rays to a 3.5 cm2 right hemithorax port. Half of each radiation dose group consumed control powdered chow, and half consumed chow containing Captopril (50 mg/kg/day) continuously after irradiation. There were time- and radiation-dose-dependent increases in all three skin reactions. Rats exposed to 10 Gy exhibited a mild and transient epilation, but no moist desquamation or neoplasia in the radiation port. In animals exposed to 30 Gy, however, epilation began at 2 weeks after irradiation, reached a peak at approximately 7 weeks, then persisted essentially unchanged through 52 weeks. Captopril had no significant effect on the epilation reaction. Two waves of moist desquamation were observed after 30 Gy. The first appeared at 3 weeks after irradiation, reached a peak from 6-10 weeks, then subsided partially but significantly from 12-26 weeks. The second wave of moist desquamation began at 26-28 weeks, often was ulcerative, and occasionally was accompanied by the appearance of tumours in the irradiated volume. Captopril significantly (p less than 0.05) reduced the severity of both phases of the moist desquamation reaction after 30 Gy, and reduced the percentage of animals exhibiting the most severe desquamation score (involving 50% of the radiation port). Of particular interest was the observation that Captopril also reduced the incidence of tumours. Of the 14 tumours detected, all were malignant (fibrosarcomas, squamous cell carcinomas), and only three (p less than 0.05) occurred in rats receiving Captopril. Multiple tumours (three cases), tumours induced by 20 Gy (three cases), and tumours appearing before 6 months (one case) were observed only in rats consuming control diet, never in Captopril-treated animals. Animals which developed tumours in the second 6 months post-irradiation exhibited significantly more severe moist desquamation during the first 6 months than did the tumour-free members of their treatment group. Thus Captopril, known to ameliorate acute lung damage in irradiated rats, also reduces chronic benign and malignant skin reactions in the radiation treatment field. PMID- 2198983 TI - Can ultrasound replace the intravenous urogram? PMID- 2198984 TI - Twenty-first annual meeting of the British Medical Ultrasound Society. Torquay, December 5-7, 1989. Abstracts. PMID- 2198985 TI - Recent advances and future projections in clinical radionuclide imaging. PMID- 2198986 TI - Pelvic haematoma following orchidectomy: a pitfall in the staging of non seminomatous germ cell tumour. PMID- 2198987 TI - Topical infusion of metronidazole in the radiotherapy of tumours of the uterine cervix: interim report on the 2 year survival. PMID- 2198988 TI - Total abdominal and pelvic ultrasound: incidental findings and a comparison between outpatient and general practice referrals in 1000 cases. PMID- 2198989 TI - Changing epidemiology and clinical aspects of hepatitis A. AB - The picornavirus responsible for hepatitis A is no longer thought directly cytopathic; it is probable that pathogenesis is dependent on T-cell mediation. Although well known to cause a generally milder illness in young children, it is now clear that the severity of hepatitis A continues to increase steadily with increasing age through adulthood also. Earlier and controversial reports of relapsing hepatitis A are now better supported by investigatory data. Cyclic epidemics are becoming less apparent in the developed world, where particular groups, such as intravenous drug abusers and those in contact with children, account for an increasing proportion of cases. Endemicity is gradually being overcome in developing countries, an effect mainly of improved sanitation, and it has been shown that hepatitis A may disappear entirely from isolated communities. PMID- 2198990 TI - Molecular biology of hepadnavirus replication. AB - Hepatitis B virus was discovered to be the causative agent of hepatitis B (serum hepatitis) almost 25 years ago. However, a detailed understanding of the biology of this clinically important virus has only developed in the last ten years. Among the problems faced by early researchers, were the very limited host range exhibited by HBV and the lack of any tissue culture system in which to propagate the virus. The advent of molecular cloning techniques and the discovery of HBV like viruses in certain animals, lead to rapid advances in the late 1970s. More recently, several systems have been described for studying hepadnavirus infection and replication in vitro, which promise to yield exciting developments in the near future. In this chapter we will review the molecular biology of HBV replication, and the contributions made by the various animal models and in vitro systems to our present level of understanding. PMID- 2198991 TI - Immunology of hepatitis B virus infection. AB - The hepatitis B virus (HBV) is believed widely to be noncytopathic in its natural host, man, although this may not be true in animal models, for example the transgenic mouse where expression of HBsAg is associated with the onset of hepatocellular degeneration and necrosis. The basis for this belief is simply that in the earlier stages of chronic HBV infection, when viral replication is most efficient, 'patients' remains asymptomatic and a liver biopsy reveals no evidence of inflammation or parenchymal liver damage. The major features of immunological interest in HBV infection are first that a proportion of those exposed to the virus become chronically infected and second that once chronic infection is established, most will gradually eliminate the nucleocapsid antigen from the liver, while the envelope antigens continue to be expressed. During the elimination of nucleocapsid antigens, many patients develop permanent liver damage. PMID- 2198992 TI - Delta hepatitis. The disease and the virus. AB - Delta hepatitis virus is a new human pathogen always found associated with hepatitis B virus (HBV) causing both fulminant hepatitis and the accelerated progression of pre-existing HBV hepatitis. The virus is coated in HBsAg and contains circular single stranded RNA genome with very high intramolecular base pairing, similar to the genomes of plant viroids, and the HDV antigen, a specific marker of HDV infection also found in the nuclei of infected hepatocytes. The genome is about 1700 nucleotides long and of minus polarity with a major constant antigenomic Open Reading Frame (ORF) which codes for the antigen. Replication of viral RNA appears to proceed by a rolling circle mechanism and specific self cleavage and self-ligation of both genomic and antigenomic HDV RNA strands has been demonstrated in vitro. HDV appears to require HBsAg for its propagation and hepatotropism but not to depend on HBV for replication. PMID- 2198993 TI - A historical perspective of mechanical ventilation. AB - The fascinating history of mechanical ventilation reveals many approaches to support failing respiration. New technologies continue to evolve. Understanding the intricacies of the patient-machine interface and the use, abuse, and mystique of certain methods of mechanical ventilation such as positive end expiratory pressure (PEEP) are considered in this article. The future promises exciting new approaches in mechanical ventilation. PMID- 2198994 TI - Negative-pressure ventilation. AB - In this review, we make the following major points: (1) Canine experiments indicate that in an experimental model of ARDS, cyclic NPV plus NEEP is as effective as cyclic PPV plus PEEP in treating arterial hypoxemia. Because cyclic NPV plus NEEP does not depress cardiac output as much as cyclic PPV plus PEEP, further study of this potential therapy is warranted. (2) At the present time, NPV has little use in neonatal medicine. (3) However, in adult medicine, NPV is efficacious for providing chronic ventilatory support in patients with neuromuscular and chest wall diseases. Additionally, the role of NPV in postoperative weaning warrants further study. (4) Some data in the literature suggest that some subsets of patients with CAL may benefit from chronic intermittent NPV therapy. However, criteria for identifying these patients have not been established. (5) Some investigators have recently demonstrated that PPV delivered via the nares can elicit VMR. Because this technique provides us with the opportunity to elicit VMR by a method other than NPV, nasal PPV provides us with a method to directly validate our presumption that improvements in COPD patients are related to VMR per se. PMID- 2198995 TI - Airway management in the critically ill patient. AB - Decisions regarding the application and care of airways in respiratory failure are important determinants of outcome in critically ill patients. Specialized procedures for institution of translaryngeal intubation in difficult circumstances, such as fiberoptic intubation, and provision of immediate surgical airway access, such as cricothyroidotomy, are requisite skills for the intensivist. The evolving application of standard techniques and advent of newer procedures for airway cannulation require extensive experience and cognitive skills in the management of tracheal intubation to enhance patient benefit and limit adverse effects from tracheal intubation. PMID- 2198996 TI - The new generation of mechanical ventilators. AB - The newest generation of mechanical ventilators has allowed increased flexibility and enhanced mechanical performance. Primary advantages of these units are improved interfacing during spontaneous breathing, improved monitoring capabilities, and increased safety by the addition of apnea/back-up ventilation during all spontaneous breathing modes. The major drawbacks of these units are their operational complexity and the inclusion of a large number of highly sensitive alarms. Finally, in spite of the scope and capabilities of these ventilators, the vast majority of patients can be very capably managed with the "mid-range" ventilators discussed as well as the majority of well maintained older generation ventilators. All the bells and whistles available on top-of-the line units do not necessarily constitute an improvement in patient care. PMID- 2198997 TI - Non-conventional techniques of ventilatory support. AB - The non-conventional techniques for ventilatory support represent a new approach to the management of patients with respiratory failure. A large number of studies indicate that these techniques can maintain adequate gas exchange under conditions in which the traditional concepts of gas transport no longer hold. We have reviewed the group of techniques, collectively called high frequency ventilation (HFV), in which the tidal volumes are much less (1 to 5 ml per kg) than those observed during conventional mechanical ventilation. Although HFV has theoretical advantages in some clinical settings, it has been shown to be superior to conventional mechanical ventilation in but a few. HFV appears to provide adequate ventilation while still allowing access to tracheal and laryngeal surgical fields. It has been successful during pneumonectomy, and in the treatment of bronchopleural fistulae. The relevance of tracheal insufflation (TRIO) of oxygen and constant flow ventilation (CFV) to the human clinical setting is uncertain. TRIO may be useful to oxygenate patients who are difficult to intubate, or TRIO could be applied for ventilation of patients involved in mass casualties. Although CFV does not maintain normal levels of PaCO2 in humans, it can provide adequate oxygenation. It might be clinically applicable during thoracic surgery, in which movement of the abdominal and thoracic contents associated with conventional mechanical ventilation is undesirable. During CFV, the lung is kept motionless with sufficient airway pressures to maintain patency of airways and alveoli. CFV is useful as a tool for studying phenomena affected by breathing. The rationale for the use of an artificial lung during extracorporeal membrane oxygenation (ECMO) or extracorporeal carbon dioxide removal with low positive pressure ventilation (ECCO2R-LFPPV) in the treatment of acute respiratory failure is to provide temporary respiratory function while the pulmonary lesion is being treated or is resolving. The factors that most limit the usefulness of ECMO are not technical but relate to the ability of the lung to recover structurally and functionally after a severe insult. Poor survival figures in the published series of ECMO in adults reflect the gravity of illness prior to treatment. However, results in neonates have been quite encouraging. ECCO2R allows less exposure of blood to the extracorporeal circuit and avoids the reduction in pulmonary blood flow associated with ECMO. Although the reported survival of adults with severe acute respiratory failure treated with ECCO2R is extremely promising, it is important to point out that none of the published reports are controlled, randomized studies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2198998 TI - Ventilator modes: old and new. AB - CPPV is an accepted standard of treatment in patients with acute respiratory failure. Because of rapid technologic advancements, new modes of ventilation have been developed. Unfortunately, this occurs at a time when there are still many controversies about the relative benefits and modes of action of CPPV. Before the proliferation of use of these newer modes in the intensive care units, documentation of the beneficial effects and safety of these modalities under controlled condition is of utmost importance. Although some of the "new" ventilatory modes (PSV, PAV) improve patient comfort and synchrony, and PAV has the potential to replace CPPV, the superiority of the "new" ventilatory modes over that of CPPV remains to be established, particularly in the area of patient survival, morbidity, and cost. PMID- 2198999 TI - Strategies to minimize breathing effort during mechanical ventilation. AB - A primary objective of mechanical ventilation is to alleviate the intolerable effort of breathing while allowing the patient to perform enough work to prevent atrophy. By assuming the workload associated with breathing, mechanical support averts ventilatory failure, prevents respiratory arrest, assures CO2 removal and pH homeostasis, while permitting the overtaxed respiratory muscles to replenish energy reserves as the primary process is addressed. Skillful manipulation of the breathing workload can often facilitate the ventilator withdrawal process. The objectives of this article are to characterize the magnitude of ventilatory work performed by the machine and patient during mechanical ventilation and to formulate a strategy for minimizing the breathing workload. PMID- 2199000 TI - The effects of mechanical ventilation on the cardiovascular system. AB - Positive-pressure ventilation may improve gas exchange, decrease the work-cost of breathing, and rest respiratory muscles, but it also will alter cardiac output and may modify blood flow distribution. Ventilation may induce these hemodynamic changes by altering systemic venous return to the RV (RV preload), pulmonary arterial pressure (RV afterload), ventricular interdependence (LV preload), or transmural LV ejection pressure (LV afterload). These interactions are magnified when the changes in lung volume and intrathoracic pressure are increased or under conditions associated with a reduced effective circulating blood volume or cardiac contractility. An understanding of these interactions is central to the effective management of the ventilator-dependent patient. PMID- 2199001 TI - Respiratory monitoring during mechanical ventilation. AB - Continuous monitoring of important respiratory indices has the potential for predicting catastrophes and for providing an opportunity for the timely institution of lifesaving measures. Pulmonary gas exchange can be assessed by indices derived from arterial blood gas measurements, but these are limited by their invasive and intermittent nature. Intra-arterial electrodes that provide a continuous recording of blood gases are under development and appear very promising. Specially designed pulmonary artery catheters permit continuous recording of mixed venous O2 saturation, whereas continuous, non-invasive recordings of arterial oxygenation can be obtained with pulse oximetry and transcutaneous electrodes. A satisfactory method of monitoring CO2 tension does not exist. Measurements of respiratory drive can be obtained at the bedside, but their clinical usefulness remains unknown. Assessment of respiratory muscle strength is helpful in determining the need for mechanical ventilation, but a practical method of diagnosing respiratory muscle fatigue remains elusive. Recordings of the airway pressure waveform, calculation of thoracic compliance, and detailed examination of the pattern of breathing are helpful in assessing pulmonary mechanics. Although respiratory monitoring provides much useful information, it does not substitute for careful bedside examination. PMID- 2199002 TI - Complications associated with mechanical ventilation. AB - A constellation of adverse effects and complications may be associated with mechanical ventilation, although in many instances the causal role of the ventilator itself has not been established. Complications occur with greater frequency than is generally appreciated, and tend to be under-reported in the medical literature. Among the potential adverse physiologic effects of positive pressure ventilation are decreased cardiac output, unintended respiratory alkalosis, increased intracranial pressure, gastric distension, and impairment of hepatic and renal function. Failure of the ventilator to cycle, of safety alarms to function properly, and of inspired gas to be properly heated or humidified are examples of equipment-related complications. Perhaps most feared among medical complications occurring during mechanical ventilation are pneumothorax, bronchopleural fistula, and the development of nosocomial pneumonia; these entities may owe as much to the impairment of host defenses and normal tissue integrity as to the presence of the ventilator per se. Finally, a variety of avoidable "misadventures," due primarily to lapses of understanding and communication among the physicians, nurses, and respiratory care practitioners managing the ventilated patient, can adversely affect comfort, morbidity, and ultimate outcome. PMID- 2199003 TI - Weaning from mechanical ventilation. AB - Although the majority of patients can be easily weaned from mechanical ventilation, a substantial minority pose considerable difficulty. These patients account for a disproportionate amount of health care costs, and they pose enormous clinical, economic, and ethical problems. The major determinants of weaning outcome include the adequacy of pulmonary gas exchange, respiratory muscle pump function, and psychological problems. Many of the physiologic indices that have been used to predict weaning outcome are frequently inaccurate. Several techniques of weaning can be used, and there are no data to suggest the superiority of one technique over another. Management of the problem patient should be directed at the underlying cause of ventilator dependency, and an organized plan should be followed. PMID- 2199004 TI - Oxygen toxicity. AB - The paradox of oxygen therapy is that it can be both life saving and life destroying. Considered as one of the most important drugs available to the clinician, its "dose," determined as the product of the oxygen concentration used and the duration of its use, must be titrated to avoid toxicity while still achieving adequate systemic oxygenation. PMID- 2199005 TI - Mechanical ventilation in the home. AB - Despite advances in the application of mechanical ventilation as a short-term, life-saving technique, intensive care units are increasingly faced with patients who cannot be weaned from ventilatory assistance and who require mechanical ventilation as a long-term, life-supporting necessity. Because of limited resources in health care facilities for the management of chronic ventilator assisted individuals, home care has become an important option. With careful selection of appropriate candidates, home care for ventilator-assisted individuals can result in not only decreased respiratory symptoms, reduction in hospitalization, and improved physiologic measures, but also an improved quality of life with substantial survival and a reduction in the costs of medical care. PMID- 2199006 TI - Early strategic never took 'no' for an answer. PMID- 2199007 TI - A computer-derived protocol using recursive partitioning to aid in estimating prognosis of horses with abdominal pain in referral hospitals. AB - In order to determine which variables are useful and accurate in estimating prognosis in horses with abdominal pain, data were analyzed from 231 horses presented at a veterinary teaching hospital. Using multiple stepwise discriminant analysis in a recursive partition model, we obtained a decision protocol that identified survivors and nonsurvivors. The prevalence of survivors was 61% in this population. The sensitivity, specificity, and positive and negative predictive values of this model were 71, 83, 87 and 65%, respectively. This decision protocol was validated by Jackknife classification and also by evaluation with a referral population of 100 horses in which the prevalence of survivors was 83%. This led to sensitivity, specificity, and positive and negative predictive values of 83, 78, 94 and 50%, respectively. PMID- 2199008 TI - Clinical trials for patients with AIDS or HIV infection. PMID- 2199009 TI - An overview of bone marrow transplantation for chronic myeloid leukemia. AB - The use of intensive therapy together with transplantation of marrow from a suitable donor is the only established curative treatment for patients with chronic myeloid leukemia (CML). However, marrow transplantation is hazardous, costly and applicable to relatively few patients. Therefore, we evaluated the results and limitations of marrow transplantation for CML and discussed new treatment strategies. We decided to select a limited number of papers that focused on the relevant issues rather than to undertake an exhaustive comparison of treatment results from different centres. Patients with CML in the chronic phase who receive marrow from a sibling with the same human leukocyte antigen type can expect to have a long-term disease-free survival rate of 50%. However, the procedure is associated with a mortality rate of 30%, mainly because of graft versus-host disease (GVHD) and interstitial pneumonitis. Moreover, because of the requirements for age and histocompatibility only 10% of patients with chronic phase CML are currently eligible. Transplantation earlier in the chronic phase (within 1 year after diagnosis), the use of marrow from matched, unrelated donors and the development of improved methods for reducing the incidence of GVHD all hold promise. In addition, the preliminary results of intensive therapy followed by transplantation with cultured autologous marrow have been encouraging. If further progress is to be made, continued optimism coupled with carefully developed and executed studies will be necessary. PMID- 2199010 TI - The BMA comes to Winnipeg. PMID- 2199011 TI - Perioperative responsibilities of the physician/geriatrician. AB - The number of elderly patients undergoing surgery is increasing. A model that identifies sources of perioperative risk to the elderly patient is presented and discussed. We suggest that the perioperative responsibility of the physician/geriatrician lies in a self-conscious examination of these sources of risk in order to maximize the likelihood of a beneficial outcome. PMID- 2199012 TI - Perioperative responsibilities of the surgeon. AB - Surgery is as effective in the elderly as in any age group and should not be denied on the basis of age. The elderly need and deserve more courtesy and respect. Meticulous attention to preoperative preparation is critical. Anticipation of problems such as hypokalemia and dependency on tranquilizers and prompt preemptive action go a long way toward the prevention of complications. Preoperative invasive monitoring in the ICU using a Swan-Ganz catheter and appropriate volume preloading will reduce operative mortality in high-risk patients. Suitable candidates are best recognized by lung function studies and blood gases in addition to a global assessment. The operation itself must be kept simple, and the surgeon needs to work swiftly but gently. The elderly require particular attention to the prevention of specific complications. Urinary catheters, nasogastric tubes, and prolonged parenteral nutrition should be avoided whenever possible. Immobility for any length of time is to be condemned. Heparin prophylaxis against thromboembolism and antibiotic prophylaxis are liberally employed. Finally, should the elderly patient develop a major complication, this complex situation must be handled with both skill and compassion. The surgeon must not lose sight of the fact that the goal is most often palliation and that quality of life is paramount. PMID- 2199013 TI - Alternatives to major surgery in the high-risk elderly. AB - The frail elderly patent with surgical disease presents a unique challenge to the geriatrician. Coexisting medical disease and increasing surgical risk coupled with a perceived reduction in benefit based on limited functional capacity or life span often make the frail elderly unable or unwilling to undergo major surgery. The many recent advances in medical therapy outlined in this review offer alternatives to major surgery in this population. PMID- 2199014 TI - Choosing the site of surgery. An overview of ambulatory surgery in geriatric patients. AB - The elderly population in the United States has been subjected to a massive experiment in mandatory outpatient surgery. Fortunately, this experiment has proven successful. Outpatient surgery of the elderly is feasible and routinely safe if common sense is used and appropriate precautions are undertaken. PMID- 2199015 TI - Anesthetic considerations in geriatric patients. AB - The increasing number of geriatric patients presenting for surgical procedures provides continuing anesthetic challenges. With an understanding of each patient's situation and communication among all the participants in the procedural chain (patient, family, and the anesthesia, surgical, and nursing teams), a well-planned and well-executed anesthetic should help ensure a favorable outcome. The complexities outlined demonstrate that there is not one best way for every patient; rather, an individualized approach is necessary. PMID- 2199016 TI - Noncardiac surgery in the elderly patient with cardiovascular disease. AB - The elderly patient with cardiovascular disease who undergoes noncardiac surgery presents a challenge to the medical-surgical team. A high prevalence of cardiac disease necessitates a preoperative in-depth search for the presence of cardiovascular risk factors and their reversal if possible. Aging is associated with an altered physiologic response to the stress of surgery as well as to anesthetic agents and perioperative medications, requiring that the elderly patient often be treated quite differently than the younger surgical patient. This article provides guidelines for the estimation of the risk of cardiac complication due to noncardiac surgery and discusses the identification and management of acute and chronic cardiovascular problems in the perioperative period. PMID- 2199017 TI - Prophylaxis for deep vein thrombosis and pulmonary embolism in the geriatric patient undergoing surgery. AB - The difficulty surrounding guidelines for the prophylaxis of deep vein thrombosis (DVT) and pulmonary embolism (PE) stems from the willingness to accept some degree of DVT in the calf, with the resultant lower risk of fatal PE, versus the risk of bleeding from a more effective prophylaxis that prevents DVT. This article reviews the etiology, risk factors, methods of prophylaxis, incidence of DVT/PE in various surgeries, and guidelines for DVT/PE prophylaxis. PMID- 2199018 TI - Perioperative psychiatric considerations in the elderly. AB - This article deals with common issues encountered in elderly persons who are medically ill. Agitation and delirium, including alcohol withdrawal syndrome, are frequently encountered problems, and useful intervention strategies are presented. Depression in this population is discussed, and a brief review of the use of antidepressants is given. Finally, the approach to and management of anxiety, with special focus on the intensive care unit setting, is summarized. Principles of pharmacotherapy in the elderly are reviewed. PMID- 2199019 TI - Perioperative renal, fluid, and electrolyte management. AB - Normal physiologic changes of aging increase the likelihood of renal-electrolyte disorders in the elderly surgical patient. The most important of these changes are a decrease in the GFR, decreased urinary concentrating ability, and narrowed limits for the excretion of water, sodium, potassium, and acid. Because of the decrease in GFR, the elderly surgical patient is at increased risk for virtually every cause of acute renal failure, an outcome associated with a mortality of greater than 50%. Certain types of surgery, especially cardiac, aortic, and biliary tract operations, are associated with a higher risk of acute renal failure than are others. The most important principles of prevention in the elderly surgical patient are to maintain normal intravascular volume and avoid hypovolemia. Meticulous attention must be paid to salt and water balance and to drug dosing. Should perioperative renal insufficiency occur, evaluation and management in the elderly patient are similar to usual practices in a younger individual. PMID- 2199020 TI - Surgical management of the hip in the elderly patient. AB - Hip surgery is the most common major orthopedic procedure performed in the elderly. The indications are fracture and pain secondary to degenerative arthritis. Patients undergoing hip replacement for arthritis have excellent outcomes with decreased pain, increased mobility, and a low mortality. Age should not be a contraindication to hip replacement, with patient selection being made on the basis of symptomatology and overall health. In hip fracture, the prognosis is more guarded. Poor functional outcome results from complications of the fracture, such as avascular necrosis of the femoral head and fracture nonunion in femoral neck fractures and instability with delayed weight bearing in intertrochanteric fractures. In addition, patients sustaining hip fracture are more likely to have significant comorbidity and subsequent perioperative complications. Pressure ulcers, delirium, deep venous thrombosis, urinary retention and urinary tract infection, and cardiac events are the most frequent complications seen. These complications can be anticipated and prevented with careful preoperative assessment and post-operative prophylactic management. A team approach including the orthopedic surgeon, primary care physician, nursing staff, and physical therapists is essential for optimal outcome. PMID- 2199021 TI - Abdominal surgery in the elderly patient. AB - The accurate diagnosis of abdominal disease is important in the elderly, both to avoid negative exploration and to plan timely and appropriate operation. Emergency abdominal surgery has a higher mortality than elective surgery and is best avoided. A definitive planned elective procedure in the well-prepared elderly patient will avoid multiple operations and reduce mortality and morbidity. PMID- 2199022 TI - Plastic surgery in the elderly. AB - Plastic surgery has an ever-increasing role in the management of medical problems in the elderly. These procedures can be performed with minimal risk to the patient in order to maximize the quality of life for these patients and their families. PMID- 2199023 TI - Eye surgery in the elderly. AB - The overall risk of eye surgery is quite low, and surgery can generally be performed in all but the sickest patients. Ambulatory eye surgery is now the rule rather than the exception and is generally well tolerated under local anesthesia. It is important for the consultant to remember those conditions that will increase morbidity and appropriately inform the ophthalmologist and anesthesiologist. PMID- 2199024 TI - Post-discharge care planning and rehabilitation of the elderly surgical patient. AB - Successful discharge planning, home care, and rehabilitation for surgical patients can be very satisfying. However, everyone involved should be aware that it can also be frustrating when, despite careful plans and organization, everything falls apart, often because the patient's disease course is different from that expected or the patient or family are not satisfied with the services. There are multiple other reasons for plans to fail, but with experience the failures should become less frequent. All too often in life we take success for granted and weigh failures twice as much. The danger of this type of thinking becomes especially important in discharge planning--successfully discharged patients may be "invisible" but the failures are back very quickly. Everyone involved in discharge planning should be made aware of the successes in order to prevent "burn out." Certain predictable complications can often be prevented or rapidly reversed, and rehabilitation is achieved by a team of varied health care providers. A home visit is often very helpful before discharge of an elderly surgical patient. PMID- 2199025 TI - Enhancement of dimethylnitrosamine-induced glutathione S-transferase P-positive hepatic foci by Clonorchis sinensis infestation in F344 rats. AB - The modifying potential of Clonorchis sinensis (CS) infestation on dimethylnitrosamine (DMN)-induced hepatocarcinogenesis was studied in male F344 rats. The metacercariae of CS were infected, 60 to each animal, by a single intragastric intubation at various times, before, during or after an 8-week period of DMN (25 ppm in drinking water) treatment. Controls were treated with DMN alone or infected with CS without carcinogen. Animals killed at the end of the 40-week experimental period showed a significant enhancing effect of CS on GST-P+ foci induction when CS was infected 4 weeks before DMN treatment, although no such influence was evident with CS infection during or following DMN exposure. The present findings suggest that CS might facilitate the proliferation of DMN induced preneoplastic lesions of liver in rats. PMID- 2199027 TI - Coffee and tea consumption in relation to the risk of large bowel cancer: a review of epidemiologic studies. AB - Most of the few epidemiologic investigations of the relation of methylxanthine ingestion to risk of large bowel cancer have concerned coffee consumption. A slightly increased risk in coffee drinkers was suggested by one study, no association by another and an inverse association by four, but there was a statistically significant trend across levels of consumption in only one of the latter studies. Based on the data on hand, there is little reason for concern that coffee consumption increases the risk. Although some evidence suggests an inverse association, the data are not compelling and a biologic mechanism is not established. There is even less information on tea consumption and the relation of consumption of this beverage to risk of large bowel cancer is unknown. PMID- 2199026 TI - The effects of the Bowman-Birk protease inhibitor on c-myc expression and cell proliferation in the unirradiated and irradiated mouse colon. AB - The levels of c-myc RNA and crypt cell proliferation were monitored in the mouse colonic mucosa following X-irradiation with and without oral administration of the Bowman-Birk protease inhibitor (BBI). Mice were divided into 4 groups and treated as follows: (A) daily gavage with water; (B) daily gavage with BBI; (C) daily gavage with water and 12 Gy of abdominal irradiation 1 day after the first gavage; (D) daily gavage with BBI and 12 Gy of abdominal irradiation 1 day after the first gavage. Samples were collected at various times after X-irradiation and ascending colon samples were taken for crypt cell proliferation analysis. The mucosa was removed from the remaining sample and total cellular RNA was isolated. The levels of c-myc mRNA underwent a time-dependent change following X irradiation. Expression of the c-myc gene was unchanged at 1 day and 3 weeks after irradiation, but was markedly elevated at 1 week after X-irradiation. BBI was found to suppress the radiation induced elevation of c-myc mRNA, while having no effect on the rate of crypt cell proliferation or body weight of the mice. PMID- 2199028 TI - Naturally-occurring age-dependent glutathione S-transferase pi immunoreactive hepatocytes in aging female F344 rat liver as potential promotable targets for non-genotoxic carcinogens. AB - Naturally occurring basophilic foci (focal hepatocellular proliferative lesions) (FHPL) in the livers of aging female F344/NCr rats could not be promoted to grow or progress into tumors after phenobarbital (PB) exposure. Instead, PB induced new unique eosinophilic hepatocellular foci and adenomas much quicker in old rats than in young rats. We now report that these foci are immunoreactive for glutathione S-transferase pi (GSTP) and that they appear to arise from some naturally occurring single and double GSTP-reactive cells and foci which occur spontaneously in the liver of aging F344 rats in an age-related fashion. PB and other nongenotoxic chemicals may act as "carcinogens" by promoting the growth (clonal expansion) of some of these putative spontaneously-initiated cells and foci into tumors. PMID- 2199029 TI - Detection of rare cells expressing shared lymphoma idiotypes in fetal spleens. AB - Monoclonal antibodies have been derived against the shared and private idiotypes of immunoglobulin expressed by human B-cell lymphomas. We performed indirect immunofluorescence assays on cells from 3 fetal spleens, 3 adult spleens and 10 hyperplastic lymph nodes with a panel of 5 monoclonal antibodies directed to private lymphoma idiotypes, 2 antibodies directed to shared lymphoma idiotypes and various positive and negative control antibodies. Rare (less than 5%) cells in the fetal spleens, adult spleens and hyperplastic lymph nodes reacted with the 2 antibodies directed to shared lymphoma idiotypes. No cells in any of the specimens were reactive with the antibodies directed to private lymphoma idiotypes. We conclude that rare cells expressing shared lymphoma idiotypes are present during fetal development and in mature lymphoid tissue. This suggests that shared lymphoma idiotypes are expressed as part of a developmental process rather than in response to a specific environmental antigen. PMID- 2199030 TI - The final common pathway of cancer. PMID- 2199031 TI - No evidence for point mutations in codons 12, 13, and 61 of the ras gene in a high-incidence area for esophageal and gastric cancers. AB - The molecular mechanisms underlying the induction of esophageal and gastric cancer are not yet understood. It is possible that different etiological factors from geographically distinct areas play a role in the onset of these cancers. Twenty-seven primary esophageal and 11 gastric cancers originating from the high incidence areas of South Africa were analyzed for the presence of ras protooncogene mutations. We found no evidence for mutations in codons 12, 13, or 61 or the H-ras, K-ras, and N-ras genes in these primary cancers. Our results indicate that etiological factors such as fungal contamination of basic foodstuffs in a high-incidence area for these cancers do not play a role in the activation of ras genes and that mutations in these genes are not directly involved in the development of primary esophageal and gastric cancers in the South African population. PMID- 2199032 TI - Modulation of IdUrd-DNA incorporation and radiosensitization in human bladder carcinoma cells. AB - 5' Amino-5'-deoxythymidine (5'-AdThd) has been demonstrated previously to antagonize dTTP-mediated feedback inhibition of purified thymidine kinase from 647V, a human bladder cancer cell line. Low concentrations of 5'-AdThd (3-30 microM) have also been shown to stimulate cellular uptake of iododeoxyuridine (IdUrd) in 647V cells at clinically relevant IdUrd concentrations (2 microM). We report that the combination of 30 microM 5'-AdThd plus 2 microM IdUrd results in a significant increase of IdUrd replacement of thymidine (dThd) (18%) in the DNA of 647V cells over that obtained by exposure to 2 microM IdUrd alone (7.9%). However, increasing the 5'-AdThd concentration to 300 microM inhibited the incorporation of IdUrd into DNA (3%). IdUrd-induced radiosensitization of 647V cells, as measured by clonogenic survival, was enhanced by coincubation with 30 microM 5'-AdThd, while 300 microM 5'-AdThd reduced the IdUrd radiosensitization. Additionally, radiation-induced single strand break generation when IdUrd was incorporated into 647V DNA, as measured by rapid alkaline elution, was also enhanced by coincubation with 30 microM 5'-AdThd, while 300 microM 5'-AdThd resulted in a decrease in the number of single strand breaks produced. In T24, another bladder cancer cell line, and SV-HUC-TT1, a tumorigenic cell line derived from SV-HUC, 3-10 microM 5'-AdThd was also able to enhance IdUrd replacement of dThd in DNA. However, no stimulation of dThd replacement by 5'-AdThd occurred in SV-HUC, a prototypic "normal" bladder urothelial cell line. Since 5'-AdThd is not a substrate for mammalian thymidine kinase and has little or no cytotoxicity in vitro and in vivo, it may be a selective modulator of IdUrd radiosensitization of human bladder carcinoma and should be tested in vivo. PMID- 2199033 TI - Formation and persistence of novel benzo(a)pyrene adducts in rat lung, liver, and peripheral blood lymphocyte DNA. AB - Male CD rats were injected with single i.p. doses of benzo(a)pyrene (B(a)P), and peripheral blood lymphocytes (PBLs), livers, and lungs were removed at various times after administration. DNA adducts were analyzed in each tissue by 32P postlabeling with nuclease P1 enhancement. Sister chromatid exchange frequencies were concomitantly measured in cultured whole blood. B(a)P-DNA adducts were observed in all three tissues from animals sacrificed between 1 and 56 days after injection. Maximal adduction levels occurred at about 4 days after administration, followed by a gradual loss of adducts over the period examined. The apparent half-lives of total DNA adducts were 15 days in liver, 17 days in PBLs, and 22 days in lung. Induced sister chromatid exchanges were linearly related to the amount of DNA adducts remaining in the PBLs at the time of harvest up to 56 days and were significantly elevated above concurrent controls up to 14 days. One of the major adducts found in each tissue was N2-(10 beta-[7 beta,8 alpha,9 alpha-trihydroxy-7,8,9,10-tetrahydrobenzo(a) pyrene]yl)deoxyguanosine. An additional novel major adduct was found in the liver DNA and is derived from the further metabolism of B(a)P-trans-7,8-dihydrodiol. A second major novel B(a)P adduct was found in the DNA of lung tissues and accounts for about 40% of the total adducts present. Experimental evidence suggests that this adduct is derived from a metabolic pathway that includes the formation of 9-hydroxy-B(a)P. PMID- 2199034 TI - Are biochemical markers for treatment-resistant schizophrenia state dependent or traits? AB - With increased understanding of antipsychotic drug treatment, the emphasis in research and clinical practice is shifting toward patients who do not respond or who respond only in part. At present the clinician can determine only after the fact whether a schizophrenic patient will respond to drug treatment. Antipsychotic drug response is seen as state dependent and may be determined by the biochemical condition of the patient. The authors have reviewed studies of biochemical measures and antipsychotic drug response. It appears that psychotic patients with elevated catecholamine release are likely to respond rapidly to neuroleptic treatment, whereas psychotic patients with lower cerebrospinal fluid (CSF) or plasma catecholamine levels are most likely to be treatment nonresponders. A dysregulation of the locus ceruleus may affect the dopamine system's responsivity to pharmacological interventions. PMID- 2199035 TI - Inadequate dosing and pharmacokinetic variability as confounding factors in assessment of efficacy of antidepressants. AB - The scientific literature on tricyclic antidepressants contains few studies on the dose-effect relationship, and this aspect of the treatment has for many years been given little attention. However, recent reviews point out inadequate dosing as an important factor in "drug resistant depressions." Tricyclic antidepressants have a narrow therapeutic range and standard doses, which are frequently recommended, will not be therapeutic in some patients and toxic in other patients. Use of flexible dose schemes, which has been customary in clinical trials, carry a considerable risk of underdosing because common side effects occur at subtherapeutic doses. Dosing according to therapeutic effect is not feasible in light of the slow and variable rate of response. Much of the difficulties in establishing a dose-effect relationship appears to be related to the considerable pharmacokinetic variability. The major source of this variability is the genetic polymorphism related to the sparteine/debrisoquine oxygenase. For some of the tricyclic antidepressants, a concentration effect relationship has been established, but almost exclusively on the basis of retrospective studies. The dose-response problem is particularly important in clinical trials. Apparent differences or equivalence between a new drug and the control therapy thus may entirely be related to differences in doses of the two drugs. For tricyclic antidepressants, the use of flexible dose schedules and poor control of compliance may often lead to underdosing and a response rate below the real potentials of these drugs. Underdosing combined with a high rate of placebo response will increase the type 2 error risk considerably and may ultimately lead to the introduction of drugs that are less effective than the classical drugs. PMID- 2199036 TI - Manipulations of sleep and phototherapy: nonpharmacological alternatives in the treatment of depression. AB - Manipulations of sleep and light (for winter depression) rapidly improve mood in 60% of depressed patients. These two unconventional treatments for depression may prove useful in patients who do not respond to drug treatments, in patients who prefer nonpharmacological treatments, or as adjuncts to drug treatments. This article reviews research on the parameters of effective sleep and light treatments and their biological mechanisms. The results of recent experiments suggest that the depressant effect of sleep may depend on thermoregulatory adjustments that occur after sleep begins. PMID- 2199037 TI - Possible mechanism of antidepressant effect of L-sulpiride. AB - L-Sulpiride is a dopamine (DA)-receptor blocker that acts as an antidepressant at low doses. We have reviewed evidence suggesting that the antidepressant effect of L-sulpiride may depend on the activation of DA transmission secondary to the blockade of DA autoreceptors. PMID- 2199038 TI - An n.m.r. and conformational analysis of the terminal trisaccharide from the serologically active glycolipid of Mycobacterium leprae in different solvents. AB - The 1H- and 13C-n.m.r. spectra of allyl 2-O-[4-O-(3,6-di-O-methyl-beta-D glucopyranosyl)-2,3-di-O-methyl-alpha-L -rhamnopyranosyl]-3-O-methyl-alpha-L rhamnopyranoside (3), a glycoside of the terminal trisaccharide found in the phenolic glycolipid I from Mycobacterium leprae, and those of the two component disaccharides, allyl 4-O-(3,6-di-O-methyl-beta-D-glucopyranosyl)-2,3-di-O- methyl alpha-L-rhamnopyranoside (1) and allyl 2-O-(2,3-di-O-methyl-alpha-L rhamnopyranosyl)-3-O-methyl-alpha-L- rhamnopyranoside (2) have been assigned completely by 1D and 2D techniques. The preferred conformations, determined by chemical shift and n.O.e. studies, were different in D2O, CD3OD, and CDCl3. The preferred conformation of 3 accorded with the results of hard-sphere exo-anomeric (HSEA) calculations. PMID- 2199039 TI - A structural investigation of the capsular polysaccharide of Escherichia coli O9:K57:H32. AB - The primary structure of the acidic capsular polysaccharide of Escherichia coli K57 was elucidated by methylation analysis and 1D- and 2D-n.m.r. spectroscopy. The repeating unit was identified as a linear tetrasaccharide having the structure shown. ----2)-beta-D-Ribf-(1----4)-beta-D-Galp-(1----3)-alpha-D-GlcpNAc ( 1----4)-alpha - D-GalpA-(1----. PMID- 2199040 TI - The structure of Escherichia coli K26 antigen. AB - The structure of the capsular antigen of E. coli K26 has been found by a combination of chemical and spectroscopic techniques to be of the "5 + 1" type shown. An important step was the simultaneous separation and identification of a mixture of neutral and acidic oligosaccharides by g.l.c.-c.i.-m.s. [formula: see text] PMID- 2199041 TI - High-sensitivity structural analyses of oligosaccharide probes (neoglycolipids) by liquid-secondary-ion mass spectrometry. AB - The sensitivity of detection and extent of information on structure obtainable by liquid-secondary-ion mass spectrometry (l.s.i.-m.s.) of neoglycolipids on the conventional target probe and directly from the surface of silica plates following t.l.c. has been assessed. Neoglycolipids were derived from malto oligosaccharides, chitin oligosaccharides, and a range of deoxyhexose-, hexose-, 2-acetamido-2-deoxyhexose-, and sialic acid-containing mammalian oligosaccharides by reductive amination using phosphatidylethanolamine dipalmitoate (PPEADP). Sub pmol amounts of the maltopentaose-PPEADP derivative applied directly to the target probe provided information on molecular weight, whereas approximately 1 pmol was required when analysed on the silica gel t.l.c. plate. With a biantennary octasaccharide derivative, the sensitivity of detection was 20-50 times lower and the other oligosaccharides had intermediate sensitivities. Information on composition and sequence was obtained readily from fragment ions, using 5 pmol of the maltopentaose derivative and 50 pmol of the octasaccharide derivative on the target probe, and 50 and 200 pmol, respectively, on the silica gel chromatogram. The optimised conditions formed the basis for characterising the structures of the components of mixtures of oligosaccharides generated from glycoproteins. PMID- 2199043 TI - Should patients with large anterior wall myocardial infarction have echocardiography to identify left ventricular thrombus and should they be anticoagulated? PMID- 2199042 TI - Granulocyte-monocyte colony-stimulating-factor augments the interleukin-2-induced cytotoxic activity of human lymphocytes in the absence and presence of mouse or chimeric monoclonal antibodies (mAb 17-1A). AB - Blood lymphocytes stimulated for 96 h with interleukin-2 (IL-2; 100 BRMP U/ml) (lymphokine-activated killer, LAK, cells) or granulocyte-monocyte colony stimulating-factor (GM-CSF) (10 ng/ml) became cytotoxic for Daudi cells. IL-2 was significantly more effective than GM-CSF. Only IL-2-activated cells killed SW948 (a human colorectal carcinoma cell line) while GM-CSF-stimulated cell did not. GM CSF and IL-2 acted synergistically in a dose-dependent fashion for induction of a highly effective cytotoxic cell population (IL-2/GM-CSF cells). Il-2/GM-CSF cells were statistically significantly more effective than LAK cells in lysing Daudi cells and SW948 (P less than 0.05). The enhancing effect was most pronounced during the first 48-96 h of activation. Incubation periods longer than 192 h did not contribute to augmented cytotoxicity. The combination of IL-2 and GM-CSF significantly increased the number of CD25+ cells compared to IL-2 and GM-CSF alone. Furthermore, IL-2/GM-CSF cells were significantly more effective in antibody-dependent cellular cytotoxicity assays (SW948 + mAb 17-1A) than LAK cells. The chimeric mAb 17-1A was significantly more effective in tumor cell lysis than the mouse mAb. Thus, combination of various biological therapeutics might be a way to enhance their antitumoral effects. PMID- 2199045 TI - Is the mitral valve prolapse patient at high risk of sudden death identifiable? PMID- 2199044 TI - Has multivessel angioplasty displaced surgical revascularization? AB - Over the years, PTCA has been proved a safe and effective therapy for single vessel CAD. Given the record of favorable results for single-vessel angioplasty, the extension of angioplasty to multivessel CAD soon followed. The successful application of PTCA to multivessel disease has been facilitated by developments in balloon, guidewire, and guide catheter technology. Success rates have been satisfactory, and complications have remained acceptable. Furthermore, as an outgrowth of an understanding of the mechanism and effect of PTCA, guidelines have been developed to aid case selection. As emphasized earlier, these guidelines should weigh heavily in deciding whether to select PTCA as a treatment modality. Presently, in our opinion, PTCA has not yet completely displaced surgery for multivessel CAD. Surgical standby is required for safe PTCA, because emergency surgery can be lifesaving and limit myocardial infarction after failed angioplasty. It is doubtful that surgery will ever relinquish its position as the treatment of choice for left main coronary artery disease. Nor will elective surgery find wide application in single-vessel disease. Whether one mode of revascularization will emerge as the most efficacious for multivessel disease related to long-term survival, limitation of cardiac events, and cost will be addressed in the analysis of the ongoing randomized trials of surgery versus angioplasty. Andreas Gruentzig established that it was possible to work within the coronary artery in an alert and comfortable patient. Interventional cardiology has experienced rapid technologic growth. Many patients formerly treated with bypass surgery can be managed effectively with angioplasty. If effective bail-out methods for acute closure are proven effective and restenosis is limited to a small percentage of patients, angioplasty in some form will further displace CABG. Until those ultimate goals are achieved, the value of angioplasty compared with bypass surgery must rest with current local experience and the eagerly awaited results of randomized trials. PMID- 2199046 TI - Is valve surgery indicated in patients with severe mitral regurgitation even if they are asymptomatic? AB - There is a natural reluctance among clinicians to recommend surgery in asymptomatic patients with cardiac disease and in patients with stenotic disease of the mitral and aortic valves; this instinct will mislead us very rarely. However, among patients with chronic volume overload of the LV, this rule-of thumb does not always apply. For truly asymptomatic patients with severe MR who clearly have normal LV function, continued medical therapy with serial monitoring of LV dynamics is a prudent alternative to the small risk of corrective surgery. However, the major challenge in addressing this problem is the definition and detection of LV dysfunction in chronic MR. Thus, for MR patients with questionable impairment of myocardial function (generally those with an SEF between 0.55 and 0.70), an examination of chamber dimensions and particularly stress-shortening relations may be necessary to detect early LV dysfunction. Should LV dysfunction be identified or should serial studies indicate an adverse trend in LV performance, a strong case can be made for proceeding with surgery. Patients with an SEF of less than 0.55 must be assumed to have LV dysfunction and analogous data from patients with chronic AR suggest that a satisfactory surgical result may be achieved if the duration of LV dysfunction is brief. Those patients with chronic MR whose disease is likely to be amenable to mitral valve repair rather than valve replacement deserve a lower threshold for corrective surgery. PMID- 2199047 TI - Should patients with mitral stenosis who are acceptable surgical commissurotomy candidates now have balloon valvuloplasty treatment? AB - This review of the surgical and valvuloplasty literature demonstrates that mitral valve morphology rather than the type of intervention determines the therapeutic results after surgical commissurotomy or balloon valvuloplasty treatment of mitral stenosis. The mechanism of dilatation and hemodynamic results of transventricular mitral commissurotomy and of mitral balloon valvuloplasty are similar. Both techniques should be considered palliative. Because the balloon catheter technique can achieve hemodynamic results similar to surgery and may delay the trauma and expense of surgery, it can be offered to patients as a primary treatment for relief of symptomatic mitral stenosis. PMID- 2199048 TI - Is valve replacement indicated in asymptomatic patients with aortic stenosis or aortic regurgitation? AB - With rare exceptions, aortic valve replacement should be performed in all symptomatic patients with hemodynamically significant aortic stenosis; however, the asymptomatic patient requires a difficult risk-benefit analysis. In most asymptomatic patients the risks of aortic valve replacement outweigh the risks of conservative therapy and careful follow-up. Symptomatic patients with chronic aortic regurgitation should undergo aortic valve replacement. Asymptomatic patients with normal left ventricular function are not surgical candidates, but aortic valve replacement should be performed in most patients with reliable evidence for left ventricle dysfunction, even if symptoms are not yet present. PMID- 2199049 TI - Does the patient with infective endocarditis and a large vegetation on the mitral or aortic valve need surgery? PMID- 2199050 TI - Should patients with atrial fibrillation be anticoagulated prior to and chronically following cardioversion? PMID- 2199052 TI - Should patients with pulmonary hypertension and increased pulmonary resistance be treated with vasodilators? PMID- 2199051 TI - Should all patients with congestive heart failure and dilated cardiomyopathy be treated with vasodilators? AB - From the discussion of these questions, several conclusions seem firm, whereas other issues await resolution. Patients with severe CHF should be treated with diuretics, digoxin, and an ACE inhibitor. In mild and moderate CHF, a diuretic should be combined with either digoxin or an ACE inhibitor--usually the latter. However, most of these patients would benefit from receiving all three drugs. Patients with asymptomatic left ventricular systolic dysfunction are at jeopardy for progressive deterioration. Angiotensin converting enzyme inhibitors and, possibly, direct vasodilators may prevent progression. In initiating vasodilator therapy, ACE inhibitors usually should be the agent of choice. Exceptions may be patients with ongoing ischemia in whom nitrates are an appropriate alternative and those who are poor candidates because of hypotension, renal insufficiency, or hyperkalemia. PMID- 2199053 TI - Is intermittent dobutamine infusion useful in the treatment of patients with refractory congestive heart failure? PMID- 2199054 TI - Should the patient with suspected acute dissection of the aorta have MRI, CAT scan, or aortography as the definitive study? PMID- 2199055 TI - Is noninvasive risk stratification sufficient, or should all patients undergo cardiac catheterization and angiography after a myocardial infarction? AB - From the foregoing discussion, it becomes apparent that although noninvasive risk stratification is a reasonable approach to assessment of patients following an uncomplicated myocardial infarction, the performance of early cardiac catheterization and angiography on nearly all such patients is not unreasonable and may in fact be the most practical approach. The basis for this rationalization may be summarized as follows: 1. Many subgroups will need early catheterization anyway a. Myocardial infarction complicated by recurrent ischemia, heart failure, or complex ventricular arrhythmias b. Patients receiving thrombolytic treatment c. "Young" patients (less than 50 years old?) d. "Older" patients (over ages 65 to 70?) in otherwise good medical condition e. Patients unable to exercise f. Patients with abnormal or inconclusive noninvasive test results (approximately 70 percent of patients) 2. Cardiac catheterization and angiography as a single test provides the two most powerful prognostic variables following myocardial infarction, namely, the extent of coronary artery disease and residual left ventricular function. This knowledge is reassuring to both physician and patient and allows for planning of optimal long-term management. 3. Certain limitations exist in noninvasive risk assessment strategies. 4. This approach need not be significantly more costly, if all tests are used wisely. The major risk inherent in the definition of the extent of coronary artery disease in all survivors of acute myocardial infarction might be the performance of unnecessary revascularization procedures (percutaneous transluminal coronary angioplasty or coronary bypass surgery). The burden rests with the individual clinician to (1) collect all useful and necessary data; (2) assess reliability and accuracy of various tests available at one's own institution; (3) avoid performing unnecessary and repetitive tests; (4) interpret the data in the proper context; and (5) counsel patients appropriately, correctly, and judiciously about their prognosis and therapeutic options. In this manner, all patients who might benefit appropriately from revascularization can be discovered early and offered this therapeutic option. Other patients can also be managed more appropriately; for example, those who are truly at very low risk (normal left ventricular function and either normal coronary arteries or "mild" coronary artery disease). However, it is most important to avoid unnecessary revascularization procedures. Although this discussion has focused on noninvasive and invasive testing following myocardial infarction, it is necessary to emphasize that comprehensive management of coronary artery disease and its complications should not be neglected in these patients; for example, control or amelioration of risk factors for coronary artery disease is mandatory in all these patients, and in their families as well. PMID- 2199056 TI - How should we manage continuing asymptomatic ischemia in patients treated for angina pectoris? PMID- 2199057 TI - Should asymptomatic patients with coronary artery disease and nonsustained ventricular tachycardia be treated with antiarrhythmic drugs? PMID- 2199058 TI - Pathophysiology of gallstone formation. AB - Research on gallstone formation has been focused on the role of supersaturated bile in cholesterol gallstone disease. But now investigators have advanced the concept of nucleation, which holds that the interaction of pronucleators and antinucleators is responsible for the formation of cholesterol crystals and the subsequent development of gallstones. Ultrasonography can identify biliary sludge, the chemical composition of which appears to depend on the type of medical disorder present. The chemical composition of sludge will determine the composition of the gallstones--either cholesterol stones or pigment stones--that eventually form. Nonsurgical interventions, such as bile acids, are effective in the treatment of cholesterol gallstones, which account for approximately 80% of cases that develop in Western populations. Bile acids are not effective in treating calcium bilirubinate stones. PMID- 2199059 TI - The management of house dust mite allergies. AB - A safe and practical home sanitation procedure for the removal of house dust mites (Dermatophagoides pteronyssinus) and their allergens is described. The severity of mite infestation was assessed with the use of the Acarex test, which measures the concentration of guanine in house dust, and all affected house textiles were then treated with an Acarosan product. The active ingredient of Acarosan is benzyl benzoate, which has been used as a scabicide for over 100 years. The results of several studies of Acarosan treatment were reviewed and it was concluded that use of the guanine test and Acarosan products allows many sensitized persons to control the concentration of house dust mite allergens in their homes. PMID- 2199060 TI - A review of the analytic performance of the Reflotron System for cholesterol testing. AB - The analytic performance of the Reflotron System for cholesterol testing has been assessed in 17 studies since 1987. The precision of the test (total coefficient of variation) ranged from 0.8% to 9.9% and was between 1% and 5% in 23 of the 27 specimen types tested. The correlation coefficient of the Reflotron with that of a reference methods was over .9 in 15 specimen types tested and over .95 in ten of 15. The type of specimen tested and the training of the test personnel affected both precision and accuracy. It is concluded that the Reflotron analyzer provides reliable and accurate cholesterol measurements. PMID- 2199061 TI - Retraction: copy choice illegitimate DNA recombination. PMID- 2199062 TI - Ribosome gymnastics--degree of difficulty 9.5, style 10.0. PMID- 2199064 TI - Three-dimensional structures of H-ras p21 mutants: molecular basis for their inability to function as signal switch molecules. AB - The X-ray structures of the guanine nucleotide binding domains (amino acids 1 166) of five mutants of the H-ras oncogene product p21 were determined. The mutations described are Gly-12----Arg, Gly-12----Val, Gln-61----His, Gln-61--- Leu, which are all oncogenic, and the effector region mutant Asp-38----Glu. The resolutions of the crystal structures range from 2.0 to 2.6 A. Cellular and mutant p21 proteins are almost identical, and the only significant differences are seen in loop L4 and in the vicinity of the gamma-phosphate. For the Gly-12 mutants the larger side chains interfere with GTP binding and/or hydrolysis. Gln 61 in cellular p21 adopts a conformation where it is able to catalyze GTP hydrolysis. This conformation has not been found for the mutants of Gln-61. Furthermore, Leu-61 cannot activate the nucleophilic water because of the chemical nature of its side chain. The D38E mutation preserves its ability to bind GAP. PMID- 2199063 TI - The three postblastoderm cell cycles of Drosophila embryogenesis are regulated in G2 by string. AB - The string (stg) locus of Drosophila encodes a factor that is thought to trigger mitosis by activating the p34cdc2 protein kinase. stg is required for mitosis early in development and is transcribed in a dynamic pattern that anticipates the pattern of embryonic cell divisions. Here we show that differential cell cycle regulation during postblastoderm development (cell cycles 14-16) occurs in G2. We demonstrate that stg mRNA expressed from a heat shock promotor triggers mitosis, and an associated S phase, in G2 cells during these cycles. Hence, differential cell cycle timing at this developmental stage is controlled by stg. Finally, we use heat-induced stg expression to alter the normal pattern of embryonic mitoses. Surprisingly, the complex mitotic pattern evident during normal development is not essential for many features of pattern formation or for viability. PMID- 2199065 TI - Direct binding of peptide to empty MHC class I molecules on intact cells and in vitro. AB - MHC class I molecules devoid of peptide are expressed on the cell surface of the mouse mutant lymphoma cell line RMA-S upon culture at reduced temperature. Empty class I molecules are thermolabile at the cell surface and in detergent lysates, but can be stabilized by the addition of presentable peptide; peptide binding appears to be a rapid process. Furthermore, class I molecules on the surface of RMA-S (H-2b haplotype) cells cultured at 26 degrees C can efficiently and specifically bind iodinated peptide presented by H-2Kb. Binding of iodinated peptide is also observed at a lower level for nonmutant cells (RMA) cultured at 26 degrees C. These experiments underscore the role for peptide in maintenance of the structure of class I molecules and, more importantly, provide two assay systems to study the interactions of peptides with MHC class I molecules independent of the availability of T cells that recognize a particular peptide MHC class I complex. PMID- 2199066 TI - Anatomy and biomechanics of the menisci. AB - The shape of the menisci and the orientation of the collagen fibers are optimal for weight bearing and shock absorption. The menisci are of clinical importance to knee biomechanics as they function to maintain knee joint stability and congruity, resist capsular and synovial impingement during knee motion, support the screw home mechanism, and distribute load over a large area of the articular surface. Because of these vital roles, an attempt should be made to save viable meniscus when performing knee surgery. PMID- 2199067 TI - Magnetic resonance imaging of the meniscus. AB - This article discusses normal anatomy of the knee and meniscal pathology using magnetic resonance imaging. A summary of the current literature is included to evaluate the sensitivity and specificity of magnetic resonance imaging and to help determine its role in the evaluation of meniscal pathology. PMID- 2199068 TI - Arthrography. Where does it fit in? AB - Although magnetic resonance imaging and arthroscopy, respectively, have become state-of-the-art techniques for imaging and treating knee ailments, arthrography remains a useful, cost-effective technique in the evaluation of the meniscal abnormalities. Arthrography is a viable procedure in the initial assessment of suspected meniscus pathology. PMID- 2199069 TI - Current status of meniscus salvage. AB - The direct repair of meniscus tears with rasp preparation of all tear surfaces, stable suture fixation, and exogenous clot injection is effective for single longitudinal tears with peripheral white rims of 4 mm and less. Radial split and flap tears at the posterior horn of the lateral meniscus can be directly repaired as well. Single longitudinal tears typically in chronic knees with peripheral white rims of 5 mm and greater may have better reliability with use of the fascia sheath. The sheath is indicated in complex tears including flaps and radial splits. A structured rehabilitation program is necessary for improved reliability of meniscus healing. Tears out in the white substance are significantly more sensitive to rapid return to weight bearing than the peripheral tears or the ligament-reconstruction portions of the procedure. Contraindications to meniscus repair would include short tears (less than 10 mm), stable partial thickness tears with less than 50% of the vertical height of the meniscus torn, and shallow radial tears of 3 mm depth or less. A posterior incision and use of the popliteal retractor at all times are necessary for protection of the popliteal neurovascular structures. PMID- 2199070 TI - Open meniscus repair. Indications, technique, and results. AB - As noted through the work of Fairbank, total meniscectomy is not a benign operation. Cox et al found that meniscectomies in canine knees lead to gross and microscopic degenerative changes. They also noted that partial meniscectomies lead to less severe degenerative changes. They believed that there was a direct relationship between the degree of degenerative change and the amount of meniscus removed. McGinty et al reported early return to function with decreased morbidity and decreased complication rates after partial meniscectomy; this was compared to both open and arthroscopic techniques for total meniscectomy. Jackson and Dandy have documented improved results of partial meniscectomy when compared with total meniscectomy in an intermediate range (average 5 to 10 years) follow-up study. Earlier studies by the senior author, Hamberg et al, and Cassidy and Shaffer have documented that meniscal repairs can heal. The more recent follow-up study of DeHaven et al has documented that repaired menisci not only heal satisfactorily but that durability and biomechanical function can also be maintained. Of course, long-term review of these same patients will be necessary to prove that successful repair will prevent the degenerative changes noted in knees following meniscectomy. PMID- 2199071 TI - Arthroscopic meniscal repair. AB - The advent of arthroscopy and advanced arthroscopic techniques has made meniscal repair the preferred approach for many meniscal tears. This article reviews the blood supply of the meniscus and discusses the supporting scientific evidence, decision making, and techniques for meniscal repair. PMID- 2199072 TI - Complications in arthroscopic meniscal surgery. AB - Arthroscopic meniscal procedures as a whole have an acceptably low complication rate. The rate is no higher than the average for all arthroscopic procedures. In the hands of experienced arthroscopic surgeons the complication rate for meniscal repair is slightly lower than that for arthroscopic partial meniscectomy. Attention to anatomic detail, knee positioning, and proper surgical technique has resulted in a significant decrease in the incidence of major neurovascular injuries. The complication rate for outside-in meniscal repair is no lower than that for inside-out meniscal repair. Further refinements in surgical technique, suture materials, and instrumentation should result in an even lower complication rate. Ongoing studies to determine when the repaired meniscus has achieved clinical stability may allow earlier range of motion and further lessen postoperative stiffness. PMID- 2199073 TI - Arthroscopic techniques to improve access to posterior meniscal lesions. AB - Unsatisfactory results following partial meniscectomy and problems related to a retained posterior horn of the medial meniscus are problems often attributed to inadequate arthroscopic partial meniscectomy. Although there are multiple techniques to gain better access to the various compartments in a truly tight knee, most of the problems in obtaining maximum visualization and instrumentation to the posterior aspects of the medial or lateral meniscus can usually be solved by adhering to a strict surgical technique that attempts to control the multiple variables encountered during arthroscopic surgery. These include the use of a tourniquet, leg holder, maximum distention of the knee provided by a large inflow cannula with large-bore tubing connected to 3-L bags, and an 18-gauge needle as a predecessor to the larger arthroscopic instruments. Of utmost importance is establishing the correct portal for the arthroscope, and it is time well spent at the beginning of the surgical procedure to verify the proper location of the arthroscope and not simply insert the arthroscope "a thumb-breadth above the joint line." Once these variables have been controlled, one can usually visualize and perform arthroscopic surgery on most meniscal lesions with minimal scuffing to the articular surfaces. PMID- 2199074 TI - Results of arthroscopic meniscectomy. AB - It would appear that arthroscopic partial menisectomy offers as good, if not better, results compared with open meniscectomy. Authors who have compared patients undergoing open meniscectomy with those undergoing arthroscopic meniscectomy have also shown that the other variables and parameters so important to the patient in the early postoperative period weight very heavily in favor of arthroscopic meniscectomy. PMID- 2199076 TI - Meniscal injuries in children and adolescents. AB - Meniscal tears occur in children and adolescents even though they have open physeal plates. Appropriate clinical evaluation and use of imaging studies is important because making a diagnosis can be difficult. Meniscectomy and partial meniscectomy are associated with long-term morbidity. Repair of meniscal tears in youths is the preferred treatment. PMID- 2199075 TI - Failed partial meniscectomy. AB - Both patients and doctors have come to expect a high rate of success from arthroscopic partial meniscectomy. Failure of this procedure may result from a number of causes, most of which can be detected preoperatively. This article elucidates these potential pitfalls so that the patient can be offered better preoperative counseling. PMID- 2199077 TI - Meniscal injuries in the cruciate-deficient knee. AB - The appropriate treatment of meniscal pathology, in the knee with an associated cruciate insufficiency, is dependent on a thorough understanding of the patient's clinical symptom complex, activity level, and the demands that that individual places on his or her knee. In the individual whose lifestyle places high demands on the knee, there is a high failure rate of meniscal repair in the presence of cruciate insufficiency. This failure rate can be obviated by either concomitant stabilization of the anterior cruciate or by significant activity modification or bracing of the knee. In those individuals in whom stabilization is not indicated because of a low demand on the knee, meniscal surgery may be performed as an isolated procedure with anticipated good results. That includes both resection of nonrepairable tears for the knee that presents primarily as locking as well as meniscal repair of appropriate lesions. In the knee with posterior cruciate insufficiency, there is greater concern about the development of degenerative changes, especially in the medial compartment. The surgeon should be aggressive in attempts at preservation of the meniscus in this setting. Posterior cruciate stabilization is less predictable given the present state of the art. However, it is recommended in the face of progressive degenerative changes. Additional considerations include appropriately timed osteotomy, especially in the face of combination injuries to the posterior cruciate and posterolateral corner as well as in future the possibility of meniscal allograft transplantation. PMID- 2199078 TI - Discoid meniscus. AB - The discoid meniscus is probably a congenital deviation that usually occurs laterally. The Watanabe classification consists of complete, incomplete, or Wrisburg ligament types. Complete and incomplete discoid menisci normally require treatment only when a tear occurs. The Wrisburg ligament type lacks a posterior capsular attachment. The preferred treatment is repair of the posterior capsular disruption with saucerization of the remaining meniscus. PMID- 2199079 TI - Meniscal cysts. AB - Meniscal cysts are cysts that occur as a direct extension, or within the substance of the meniscus. The incidence varies in reports from 1% to 20% and are much more common laterally. They usually present as joint-line pain, swelling, or both in young adult men, and are often associated with meniscal tears. The exact etiology of meniscal cysts is unknown. A myxoid degenerative process is identified histologically. There is often a history of precedent trauma. Diagnosis is often suspected clinically and can be confirmed by arthrogram, CT, or MRI when necessary. Conservative treatment in the patient with few symptoms is recommended. Should the cyst become significantly symptomatic, it is necessary to treat the meniscal pathology to prevent a cyst recurrence. At the present time it is our recommendation that this be done by arthroscopically resecting the meniscus back to normal meniscus and either aspirating and injecting the cyst with steroid or local cyst excision if the aspiration and injection fails. If no meniscal tear is documented at arthroscopy, exploration and excision of the cyst are recommended. PMID- 2199080 TI - [Jiri Josef Camel, pharmacist and botanist]. AB - Jiri Josef Camel (1661-1706), a pharmacist and botanist, was born in Brno, educated at a grammar school and then joined the Jesuit Order as a laic brother. He worked in the college pharmacies in Brno, Jindrichuv Hradec and Cesky Krumlov. In 1687 he left for a religious mission to the Philippine Islands, where he worked for 17 years in a hospital as a pharmacist. He died in Manila in 1706. He wrote 19 treatises, in which he acquainted European medicine and pharmacy with the flora and fauna of the Philippines. Camel sent his papers to London to J. Ray, the then most distinguished authority in botany. Ray published them in the 3rd volume of Historia Plantarum in 1704. The most valuable part of his work are drawings of plants, published by Petiver in the journal Gazophylacei naturae et artis (1702-1709). More than 400 of them have survived till nowadays in the collection of the British Museum. Further 260 drawings were acquired in the course of years by the University Library in Louvain. PMID- 2199081 TI - [Thromboxane and prostacyclin in endotoxin-induced lung injury]. AB - Hypotension, respiratory failure and ARDS-like pulmonary morphological changes were induced by given continuous intravenous infusion of E. coli endotoxin (1-1.5 micrograms.kg/h) in goats. During endotoxin infusion, plasma TXB2 level rose markedly with peak at 0.5 h and then lowered, while 6-keto-PGF1 alpha elevated progressively with its highest level before death, and correlated with blood pressure and survival times negatively. So we suggested that prostacyclin may be one of the factors responsible for hypotension and death in late period of endotoxin induced shock and lung injury. PMID- 2199082 TI - [Advances in the use and mechanism of action of theophylline]. PMID- 2199083 TI - Glutathione S-transferases in relation to their role in the biotransformation of xenobiotics. AB - The glutathione S-transferases (GST) are a family of isoenzymes serving a major role in the biotransformation of many reactive compounds. The isoenzymes from rat, man and mouse are divided into three classes, alpha, mu and pi, on the basis of similar structural and enzymatic properties. In view of the fact that the individual isoenzymes demonstrate differential though overlapping substrate selectivities, the extent to which biotransformation occurs is dependent on the actual profile of isoenzymes present. Consequently, both genetic factors as well as external factors causing changes in the levels or activities of individual isoenzymes are of relevance with respect to an individual's susceptibility towards electrophilic compounds. This review article deals with a number of determinants of GST isoenzyme patterns and/or activities, including tissue distribution, developmental patterns, hormonal influences, induction and inhibition. In addition, current knowledge on specific properties of class alpha, class mu and class pi isoenzymes is presented. PMID- 2199084 TI - Does vitamin E prevent retinopathy of prematurity in low birth weight babies? PMID- 2199085 TI - Toxic polyneuropathies. PMID- 2199086 TI - Synthesis of biologically active pentapeptide analogs of the N-terminal part of lipoprotein from the outer membrane of Escherichia coli. PMID- 2199087 TI - Micro-enzyme immunoassay of vasoactive intestinal polypeptide (VIP)-like immunoreactive substance in bovine milk. AB - A sensitive and specific enzyme immunoassay for vasoactive intestinal polypeptide (VIP)-like immunoreactivity was developed with the use of synthetic carboxy terminal (C-terminal) fragment (residue 11-28) of porcine VIP conjugated with beta-D-galactosidase and a second antibody-coated immunoplate. Using 4 methylumbelliferyl beta-D-galactopyranoside as a fluorogenic substrate, the minimum amount of VIP-like immunoreactive substance (VIP-IS) detectable by this method was 0.1 fmol/well (2.5 pmol/l). The level of VIP-IS in bovine foremilk was above 100 pmol/l, which was more than eightfold higher than that in normal milk. PMID- 2199088 TI - Induction of differentiation of human leukemia cells by various combinations of cytokines and low-molecular-weight inducers. AB - To explore agents for differentiation therapy of leukemias, various combinations of cytokines and low-molecular-weight inducers were examined for differentiation inducing activity toward three kinds of human leukemia-derived cell lines. The strongest differentiation inducing activity on promyelocytic HL60 cells and histiocytic U937 cells was obtained by combining recombinant tumor necrosis factor (rTNF), interferon-gamma (IFN-gamma), retinoic acid (RA), and 1 alpha,25 dihydroxyvitamin D3 (1 alpha,25(OH)2D3). For myeloblastic ML1 cells, the combination of rTNF, IFN-gamma, and RA had the strongest differentiation-inducing activity. PMID- 2199089 TI - The effects of new cytochalasins from Phomopsis sp. and the derivatives on cellular structure and actin polymerization. AB - The effects of ten 10-phenyl-[11]cytochalasins produced by Phomopsis sp. including novel compounds having 5,7- or 6,7-glycol structures and their derivatives, on the cell morphology and actin distribution in C3H-2K cells, as well as on lymphocyte capping and actin polymerization, were examined. The structure-activity relationship reported in the previous papers has been confirmed. The novel glycol type compounds showed little or no activity, suggesting the importance of the perhydroisoindol-1-one nucleus for the manifestation of the cytochalasin actions. PMID- 2199090 TI - [Effect of ke-tang-Ling administration on the function of pancreatic islets cells in non-insulin-dependent diabetes mellitus]. AB - Radioimmunoassay methods were modified for insulin(IRI), C-peptide (IRCP) and glucagon (IRG) in the clinical investigation on normal subjects and 38 patients with non-insulin-dependent diabetes mellitus (NIDDM). In the control group, the peaks of glucose and IRI appeared 1 hour after glucose was taken. IRCP peak, however, appeared 1 hour later. IRG showed its maximum value on fasting and then reached its lowest point at the second hour after glucose loading. The authors' interests were focused on the changes of blood glucose, IRI, IRCP, and IRG in oral glucose tolerance test (OGTT) before and after Ke-Tang-Ling (KTL) was administered in NIDDM. The results demonstrate that the glucose levels and undercure areas at various phases in OGTT were significantly decreased (P less than 0.01) in comparison of before and after the treatment with KTL in NIDDM (including obese and non-obese groups). In non-obese group, however, IRI, IRCP, and their undercure were remarkably increased (P less than 0.01). In obese group their values were decreased. It suggests that KTL plays a therapeutic role in decreasing blood glucose in non-obese NIDDM. The mechanism involved in this process may be related to its stimulating effect. IRG levels were decreased also (P less than 0.01) after the treatment with KTL in both obese and non-obese NIDDM, suggesting an inhibitory effect on glucagon secretion from alpha cells in pancrease. PMID- 2199091 TI - [Prostaglandins and traditional Chinese medicine]. PMID- 2199092 TI - Eosinophil granule major basic protein in contact lenses of patients with giant papillary conjunctivitis. AB - Conjunctival reaction to substances deposited on soft contact lenses is thought to be important in the development of contact lens-associated giant papillary conjunctivitis (GPC). Eosinophil granule major basic protein (MBP), a potent cytotoxin released by eosinophils, has previously been demonstrated in conjunctiva from patients with GPC. We therefore evaluated soft contact lenses from ten patients with GPC for the presence of MBP by means of an indirect immunofluorescence assay. Deposition of MBP was demonstrated in lenses from one patient, the only subject with a history of atopy. The results suggest that MBP deposits on nonionic, low water content lenses are unlikely to play a role in the development of GPC, except, perhaps, in patients with atopy. PMID- 2199093 TI - Quantitative determination of IgM-rheumatoid factor by enzyme immunoassay- standardization using a serum from a rheumatoid arthritis patient. AB - A method to standardize the quantitation of IgM-rheumatoid factor (RF) by enzymeimmunoassay (EIA) is presented. Serially diluted sera from rheumatoid arthritis patients were added to immobilized human IgG, and bound IgM-RF was detected by addition of horseradish peroxidase labeled anti-human IgM (HRPOaM). The concentration of IgM-RF which produced half of the maximal absorbance at 492 nm given by a saturating concentration of IgM-RF in the EIA plate, was defined as 1 U/ml. The IgM-RF values of test samples were measured as the dilution of the sample which provided half-maximal absorbance. The IgM-RF values determined by this method coincided with those determined by referring to a standard curve made from a serum containing known amounts of IgM-RF. Differences in IgM-RF values, which were caused by varying preparations of horseradish peroxidase anti-IgM (HRPOaM) were corrected for the binding capacity of each preparation to various concentrations of human IgM adherent to the plate. The IgM-RF values determined by this method correlated well with the RF values determined by latex photometric immunoassay (r = 0.956, p less than 0.001). IgM-RF values determined by EIA were converted into WHO-units by an empirical formula described. The data observed suggest that the method here reported can standardize IgM-RF values obtained by EIA. PMID- 2199094 TI - Lessons about autoantibody specificity in systemic lupus erythematosus from animal models. PMID- 2199095 TI - Differential expression of the calcium-binding proteins MRP8 and MRP14 in granulomatous conditions: an immunohistochemical study. AB - MRP14 and MRP8 are well-characterized calcium-binding proteins present in myeloid cells and mononuclear phagocytes. These antigens can easily be visualized in paraffin-embedded tissue, making use of monospecific polyclonal antibodies. This study evaluates MRP14 and MRP8 expression in mononuclear phagocytes in various granulomatous conditions. MRP14 is strongly expressed in all granulomatous conditions. MRP8 is variably expressed. Mononuclear phagocytes in granulomas of foreign body type, cat-scratch disease and erythema nodosum strongly express MRP8. In contrast, MRP8 expression is weak or absent in mononuclear phagocytes of sarcoidosis and tuberculosis. These results show differences in immunophenotype between non-phagocytic mononuclear phagocytes in delayed hypersensitivity type granulomas and phagocytic mononuclear phagocytes in non-hypersensitivity and non immunological granulomas. PMID- 2199096 TI - A phenotypic study of B lymphocyte subpopulations in human bone marrow. AB - The regulatory mechanisms that monitor the size of the peripheral B cell pool and determine cell death or survival are poorly understood. In rodents B lymphopoiesis is maintained at a high rate throughout adult life, and under resting conditions there is little recruitment into the long-lived peripheral pool; it therefore follows that most newly formed B lymphocytes have a very short lifespan. The maturation stages of B lymphopoiesis in humans and in experimental mammals appear to be similar. We have determined the phenotype of sIgM- and sIgD expressing cells from normal adult human bone-marrow and peripheral blood by dual immunofluorescence with an extensive panel of monoclonal antibodies representative of major B cell clusters, in order to identify antigenic differences that may play a regulatory role. Antibodies of the CD21, CD22 and CD9 clusters, the unclustered restricted B antibody 7-F-7 and anti-IgD were reactive with different proportions of sIgM+ cells in blood and bone marrow; 29.5% (range 5-60%) of sIgM+ cells in marrow were sIgD- and most of these cells were also CD21 and CD22-, thus defining a unique marrow population. However, newly formed and mature re-circulating cells comprising the sIgM+sIgD+ population could not be distinguished by the panel of antibodies. PMID- 2199097 TI - Identification of protein components reactive with anti-PM/Scl autoantibodies. AB - The PM/Scl antigen from mammalian cells has been characterized as a nucleolar and nucleoplasmic molecular complex containing at least 16 polypeptides ranging in molecular weight from 110 to 20 kD. Of these polypeptides, we have found those of 68, 39 and 20 kD to be in a phosphorilated form. Whereas the entire complex was precipitated by all the anti-PM/Scl sera tested, in immunoblots the antibodies specifically recognized determinants on the 110-kD protein. This protein was immunoprecipitated more preferentially from nucleoli extracts than from total cell extracts. Moreover, this protein disappeared from the immunoprecipitates when treated with DNAse. Likewise, the immunoblot reaction of the specific antibodies with the 110-kD protein was abolished by treatment of the extracts with DNAse and trypsin, and was resistant when extracts were treated with RNAse. Affinity-purified antibodies from this protein selectively stained the nucleoli and the nucleoplasm of the mammalian cells. Moreover, when the cultured cells used in immunofluorescence were treated with DNAse, the affinity purified antibodies from the 110-kD protein gave negative fluorescence. However, when whole anti-PM/Scl sera were used, a nucleolar and nucleoplasmic staining was found. We conclude that the 110-kD protein has at least one of the autoimmunogenic epitopes of the PM/Scl antigen, recognized by all anti-PM/Scl sera tested. Other epitopes differing in their DNAse sensitivity may also be present in the PM/Scl antigen. PMID- 2199098 TI - Autoantibodies to epithelial cells in patients on long-term therapy with leucocyte-derived interferon-alpha (IFN-alpha). AB - During routine screening for anti-nuclear antibodies, using rat liver tissue as substrate, a reactivity against bile duct epithelium was observed in sera from carcinoid tumour patients given human leucocyte-derived IFN-alpha (HuLe IFN alpha). In a retrospective study, initiated by this observation, the development of serum antibodies to bile duct epithelium was observed in nine out of 12 patients with carcinoid tumours and in three out of 14 patients with hairy-cell leukaemia during their treatment with HuLe IFN-alpha. However, no bile duct reactivity was observed in sera from carcinoid or hairy-cell leukaemia in patients given recombinant IFN-alpha. When analysing the reactivity of positive sera against a panel of rat and human tissues, a uniform reactivity was observed against simple epithelial cells lining the gastrointestinal tract, pancreatic secretory ducts, fallopian tube, kidney tubuli, mesothelium and also against carcinoid tumour cells. The mechanisms promoting autoreactivity against this simple epithelial cell autoantigen is so far unknown. The cytoplasmic as well as the restricted staining pattern of simple epithelial cells may indicate autoreactivity against certain cytoskeletal intermediate filaments, such as cytokeratin 19, 18 and 8, known to be exclusively present in simple epithelial cells and tumours derived from them. PMID- 2199100 TI - Interleukin-6 production by tumor necrosis factor and lipopolysaccharide stimulated rat renal cells. AB - Interleukin-6 (IL-6) is produced by various cell types, including monocytes, fibroblasts, and endothelial cells. IL-6 has also been detected in the urine of normal and renal transplant patients. Thus, the possible production of this cytokine by glomeruli and mesangial cells was investigated. Rat glomeruli were obtained by serial sieving of cortical homogenates of blood-free kidneys. Mesangial cells were obtained from the glomeruli and cultured under standard methods in RPMI 1640 medium containing 15% fetal calf serum. Glomeruli or confluent monolayers cells were then incubated in RPMI 1640 for 18 hr, in the presence or not of tumor necrosis factor-alpha (TNF alpha), lipopolysaccharide (LPS), or platelet-activating factor (PAF). IL-6 activity was measured using the IL-6-dependent cell line subclone (B 9-9) and expressed with respect to a standard curve established with recombinant IL-6. Glomeruli generate IL-6 upon TNF alpha (100 ng/ml) and LPS (1 microgram/ml), 11,500 +/- 3000 and 22,000 +/- 7500 U/ml, respectively. Nonstimulated mesangial cells produced 50 +/- 5 U/ml (mean +/- SEM, n = 4) of IL-6. TNF alpha (1 ng/ml) and LPS (1 microgram/ml) induced the production of 800 +/- 90 and 40,000 +/- 5000 U/ml, respectively (n = 4). In contrast, PAF (0.1 nM-1 microM) did not increase IL-6 production from glomeruli or mesangial cells. These results demonstrate that renal cells spontaneously generate minimal amounts of IL-6 and that this production is significantly increased by TNF alpha or LPS. A synergy between LPS and TNF alpha was induced in glomerular cells with 10 ng/ml of TNF alpha and graded concentrations of LPS. Thus, the production of IL-6 by glomerular cells and its modulation by other cytokines or endotoxins may play a role in the local immunological processes leading to immune glomerular diseases. PMID- 2199099 TI - Kinetics and pathogenicity of autoantibodies induced by mercuric chloride in the brown Norway rat. AB - Repeated low-dose injections of mercuric chloride (HgCl2) in the brown Norway (BN) rat result in polyclonal activation which includes the induction of anti glomerular basement membrane (GBM) autoantibodies. We examined the kinetics of various autoantibodies produced in vivo, general features of polyclonal activation such as total IgG levels and immune complex formation, and the relationship between organ specific autoimmunity and tissue injury in the kidney and thyroid. The production of immune complexes and autoantibodies to GBM and thyroglobulin was short lived, and the increase in levels of total IgG and antibodies to ssDNA and dsDNA was prolonged; the antibody response to collagen types I and II was intermediate in duration. Autoantibodies induced by HgCl2 caused only mild and variable tissue injury in the kidneys and did not induce abnormalities in the thyroid. These studies demonstrate that immunostimulation by mercury may result in the formation of a range of autoantibodies, with variable kinetics and pathogenicity. PMID- 2199101 TI - The history of dermatologic liposuction. AB - Dermatologists have been involved in liposuction even before its introduction into the United States. Liposuction has rapidly become part of the dermatologic surgeon's armamentarium. Dermatologic surgeons have been innovators in teaching and research in liposuction. They have been largely responsible for developments in fat transfer surgery. PMID- 2199102 TI - The biochemistry and development of adipose tissue and the pathophysiology of obesity as it relates to liposuction surgery. AB - It is clear that central obesity is a strong predictor of multiple health risks. It appears likely that much of the influence for the preferential deposition of fat in these various stores is related to sex hormones, although other factors clearly play a role, including genetic, environmental, nutritional, and other factors. Whereas a great deal has been discovered about these relationships in the past 10 years, further study is necessary to clarify them and determine what role dietary and surgical interventions may play in the prevention and reversal of those risk factors. PMID- 2199103 TI - A regional approach to patient selection and evaluation for liposuction. AB - Any area of the body where the deformity is due to regional excess fat and where there is overlying good skin tone is presumably amenable to body contouring by liposuction. It is an understandable temptation to attempt to remove large quantities of fat without major surgery and without noticeable scars. With experience, the surgeon will be able to estimate preoperatively the amount of fat that should be removed. However, liposuction is a procedure that requires conservatism because overzealous fat removal can generally leave unsightly permanent sequelae. Careful patient selection and proper identification of the correct indications of the technique are of paramount importance in achieving good aesthetic results and in avoiding complications. The ideal candidate is young, with good skin tone, moderate localized fatty deposits, and realistic expectations. There is certainly a wide range of patients who will benefit from the use of liposuction, and the average patient with less-than-ideal indications is more commonly encountered. The poor candidate is obese or has a significant deformity, poor skin tone, and, ironically, the most unrealistic expectations. Old age is not an absolute contraindication, although with increased age there is a concomitant decrease in elastic fibers, resulting in decreased capability to adapt a new contour. However, many patients "past their prime" will also have an acceptable cosmetic result and are particularly pleased with their changed, clothed silhouette. Appropriate patient selection, appreciation of the underlying anatomy, and judicious surgical technique are all essential for optimal results and patient satisfaction. Liposuction as described, either alone or as an adjunct to other procedures, allows for optimal aesthetic correction of figure faults due to adipose tissue. PMID- 2199104 TI - Perils and pearls of liposuction. AB - Facial and body liposuction has become a liposculpturing technique. As is usually the case, the more one performs a particular procedure, the more one realizes its difficulties, dangers, and challenges. The surgeon should never perform liposuction in a routine and casual manner. Such an approach can only lead to problems because each patient has different requirements. The goal of this chapter is to inspire the reading physician to approach each case as if it were the first one, i.e., with a great deal of prudence. This will lead to better results and fewer complications. PMID- 2199105 TI - The tumescent technique. Anesthesia and modified liposuction technique. AB - Using the tumescent technique, liposuction can remove large volumes of fat with minimal blood loss. A maximal safe dosage of dilute lidocaine using the tumescent technique is estimated to be 35 mg/kg. The slow infiltration of a local anesthetic solution of lidocaine and epinephrine minimizes the rate of systemic absorption and reduces the potential for toxicity. Dilution of lidocaine (0.05% of 0.1%) and epinephrine (1:1,000,000) further delays absorption and reduces the magnitude of peak plasma lidocaine concentrations. Using the tumescent technique for liposuction, peak plasma lidocaine levels occur 12 hours after the initial injection. Clinically significant local anesthesia persists for up to 18 hours. For liposuction, it is not necessary to use local anesthetics, which are longer acting and potentially more cardiotoxic than lidocaine. PMID- 2199106 TI - The tumescent technique for liposuction surgery. AB - The tumescent technique, developed by dermatologists, has revolutionized the approach to liposuction. It has eliminated concerns about blood loss, fluid replacement and fluid shifts, and the risks and morbidity of general anesthesia. It has also significantly decreased the cost of liposuction by eliminating the need for general anesthesia, an anesthesiologist, a hospital or outpatient operating room, and the need for blood transfusion. PMID- 2199107 TI - Gynecomastia. Treatment by liposuction subcutaneous mastectomy. AB - Gynecomastia is a common finding in both adolescents and mature adult males. The previous surgical techniques of direct subcutaneous mastectomy were associated with high frequency of complications and unsatisfactory aesthetic results. Application of liposuction techniques to the prepectoral region has provided an effective and safe technique for reliably contouring and reducing the prepectoral region. The technique described in this article includes proper placement of the incision, the injection of low-dose Xylocaine and epinephrine, and the utilization of three different types of cannulas to significantly reduce the tissue mound. The author has operated upon 60 patients utilizing this technique without having a single operative complication. PMID- 2199108 TI - Liposuction for treatment of axillary hyperhidrosis. AB - Axillary hyperhidrosis is a common and often troublesome problem. Current therapy includes topical antiperspirants, systemic anticholinergic medications, iontophoresis, and surgery. Axillary liposuction promises to be the surgical treatment of choice for those patients refractory to other modalities. PMID- 2199109 TI - Liposuction of lipomas. AB - When lipomas reach 4 cm or more in size or are multiple, liposuction becomes an excellent alternative to excisional surgery. The basic concept is that fat lobules are bluntly broken down or curetted by a cannula and then removed through the cannula's aperture by a vacuum force generated from a suction machine. There are few minor sequelae, and these are rarely of a prolonged nature. The benefits of liposuction are decreased surgical time, a shorter scar, a better final contour, and the ability to remove several lipomas through one opening. In addition, liposuction surgery is a useful modality for the removal of lipomas because of the low recurrence rate and minimal malignant potential of these tumors. PMID- 2199110 TI - Flap elevation and mobilization by blunt liposuction cannula dissection in reconstructive surgery. AB - One may accomplish certain closures without tension or distortion using blunt liposuction cannula dissection with or without suction-assisted lipectomy. If closure cannot be accomplished with adequate undermining and an appropriate flap design, the surgeon may first aspirate fat to allow use of the focally expanded skin over the fat. If still unsuccessful, fibrous neurovascular septae are progressively sacrificed as necessary to allow adequate movement and closure. Preservation of the maximal number of blood vessels and nerves within the flap is a given fact. These techniques provide more rapid and safe methods for elevating flaps with significantly less morbidity than sharp dissection methods alone. PMID- 2199111 TI - The safety of dermatologic liposuction surgery. AB - The safety of liposuction surgery begins with appropriate preoperative evaluation and patient selection. Operative considerations include the type of anesthesia used, the volume of fat aspirated, and the liposuction technique utilized. Results from a recent survey revealed that liposuction surgery can be extremely safe when done under local anesthesia with conservative fat removal. PMID- 2199112 TI - The effects of interleukin-1 on articular cartilage destruction as observed in arthritic diseases, and its therapeutic control. AB - At present there is substantial evidence to suggest that interleukin 1 (IL-1) may act as a key mediator in the normal physiologic regulation of cartilage as well as in the pathogenesis of cartilage destruction in arthritic disorders. IL-1 induces stimulation of chondrocyte catabolism and alters chondrocyte biosynthesis in articular cartilage. These actions of IL-1 may lead to destruction and inappropriate repair following degradation of the cartilage matrix. Moreover, IL 1 induced biological activities in chondrocytes may be influenced by growth factors (e.g. fibroblast growth factor, insulin-like growth factor, transforming growth factor-beta), guanine nucleotide proteins, or other cytokines. With respect to the widely suggested potential significance of IL-1 in arthritis, pharmacological control of IL-1 action is of important clinical relevance. Today the therapeutic control of IL-1 induced effects in articular cartilage destruction as observed in arthritic diseases can be divided into drugs which affect IL-1 production, drugs which modify or block the IL-1 effect before stimulation of the target cell, or drugs that interfere with the IL-1 induced effects, e.g. steroidal drugs, non-steroidal anti-inflammatory drugs, immunoregulatory drugs or class-specific proteinase inhibitors. However, these drugs do not specifically block IL-1 activity. For the development of therapeutic agents capable of specifically blocking IL-1 effects, a better understanding of IL-1 induced activities is needed. In conclusion, knowledge about chondrocyte metabolic and regulatory alterations would be beneficial in unraveling the events that take place in arthritic diseases and would favor therapeutic research for agents that might arrest the progressive destruction of articular cartilage in pathological conditions. PMID- 2199114 TI - Roentgenographic assessment of the biologic fixation of porous-surfaced femoral components. AB - Certain roentgenographic signs have value in predicting the fixation of a cementless femoral component to bone by osseointegration. Other signs have value in predicting the gross stability of a cementless femoral component. The authors have determined the specificity and sensitivity of the signs for osseointegration in cases in which the histologic fixation has been confirmed after implant removal. The authors have also determined the specificity and sensitivity of the signs for gross implant stability in cases in which the stability has been confirmed at reoperation. Statistical methods were used to determine a numeric value for each of these roentgenographic signs, and these values were combined into a score. The score was divided into fixation by osseointegration and mechanical implant stability. The two scores were then combined into an overall score. When signs of osseointegration were present, the implant was always stable, and the overall scores were the highest. When signs of osseointegration were absent, the mechanical stability varied, and the scores were lower. A neutral or slightly negative score correlated with failed osseointegration but secondary successful implant stabilization. A very low negative score correlated with gross implant instability. To confirm the validity of the scoring system, the two-year postoperative score was determined for 1005 cases in which the clinical outcome was known. A strong correlation between the presence of symptoms and a low score confirmed the value of the scoring system for diagnosing implant loosening as the cause of symptoms. As a second test, the two-year and five-year postoperative results were compared in the same patients. A high two-year score correlated with durable implant stability through five years. A low two-year score correlated with a higher incidence of late symptomatic loosening. PMID- 2199115 TI - The development of orthopedic certification in the United States. AB - The development of medical education standards and state licensure requirements occurred simultaneously in the 1900s. The result was that annual state licensure became the physician's certification. Eventually, the explosion of scientific knowledge due to hospital-based clinical practices and stimulation from national societies led to specialization within medicine. Primary specialty boards were organized in the 1930s to issue credentials and define qualifications for specialists. Just as licensure became the certification of a physician, primary boards became the certification of a physician specialist. Certification has become progressively more important in relationship to individual patients, national societies, hospitals, and third-party carriers. Recertification is the recognition by a primary board of a diplomate's continuing qualifications. The majority of primary boards have plans to institute recertification in order to evaluate pertinent cognitive knowledge of a diplomate and to respond to inadequate ongoing peer review. The expansion of scientific and technical knowledge, which led to specialization in the 1930s, inevitably has led to subspecialization. Orthopedic surgeons are using a wide range of fellowships, especially those just completing their residency education. The first certificate of added qualifications for orthopedics was in surgery of the hand. PMID- 2199113 TI - Is onset type evaluated during the first 3 months of disease satisfactory for defining the sub-groups of juvenile chronic arthritis? A EULAR Cooperative Study (1983-1986). AB - This study represents an attempt to collect observations from co-operating countries to evaluate the previously suggested criteria for juvenile chronic arthritis during the onset periods 0-3 and 3-6 months, preferably studied prospectively. Only 267 of 378 forms returned were satisfactory for inclusion because of failure to observe exclusion criteria or insufficient information. Despite this it was possible to conclude that systemic disease represented 25% of the group and that these features tended to decline during the 6 month period. Gut inflammation was seen in 4.5% and the frequency of chronic iridocyclitis increased during the observation period to 4.5%. Variation in joint state during this period suggests that course classification may be important, as 23 of 118 who were pauciarticular at 3 months became polyarticular by six months, but only 46 of 76 who were polyarticular at 3 months remained in this state at six months. PMID- 2199116 TI - Steroid-related osteonecrosis of the knee. Two case reports and a literature review. AB - Steroid-related osteonecrosis of the knee has been only rarely reported, especially without concomitant hip involvement. Two such cases are documented with correlated roentgenographic and magnetic resonance imaging. A comprehensive review of the literature illustrates the diverse circumstances in which this rare condition may occur. PMID- 2199117 TI - The accreditation of graduate educational programs in orthopedic surgery. AB - The development and evaluation of graduate medical education in the United States from the late 19th century to the present are founded on the structure, role, and function of the accrediting bodies (the Accreditation Council for Graduate Medical Education and the Residency Review Committees). The general and specific requirements for accreditation of orthopedic programs, the processes for accreditation of existing and new residency programs, and the current status of fellowship accreditation are continuously under evaluation. PMID- 2199118 TI - Eosinophilic granuloma. The management of solitary lesions of bone. AB - Solitary eosinophilic granuloma (EG) lesions of bone can represent diagnostic and treatment dilemmas for the orthopedic surgeon. A retrospective review of one institution's experience with isolated EG skeletal lesions over a 30-year period was undertaken. Solitary lesions responded well to most treatment modalities (e.g., curettage, excision, and irradiation) and infrequently resulted in functional impairment. While EG involvement in bone can be a manifestation of a systemic histiocytosis, single-focus skeletal involvement appears to be a benign pathophysiologic process. PMID- 2199119 TI - Acute septic arthritis in infancy and childhood. AB - Despite intensive study of acute septic arthritis in infancy and childhood, poor outcomes continue to occur. Failures are often due to delayed diagnosis and inadequate therapy, but can be due to factors beyond physicians' control such as associated osteomyelitis and occurrence during infancy. Recent advances in the understanding and management of septic arthritis include: (1) demonstration of beneficial effects of continuous passive motion in rabbits; (2) identification of inflammatory mediators of cartilage destruction and their respective sources; (3) recognition of changing patterns of pathologic organisms; (4) evolution of new antibiotics and standards for oral and home intravenous therapy; (5) development of arthroscopic debridement of septic knees; and (6) further refinement of indications for aspiration-irrigation versus open surgical drainage of septic joints. Permanent sequelae from septic arthritis can only be prevented by early diagnosis and aggressive treatment. PMID- 2199121 TI - Fibroblast growth factor. Chemical structure and biologic function. AB - Basic and acidic fibroblast growth factor (FGF) are two closely related growth factors that interact with the same receptor. Structurally related to FGF are five different oncogenes that have been involved in mammary, stomach, and bladder cancers but whose precise functions in physiologic processes are presently unknown. Both basic and acidic FGF exert similar biologic effects on a wide range of mesoderm- and neuroectoderm-derived cells, acting both as morphogens and mitogens. In addition, basic FGF has been shown to act as a ventrovegetalizing factor, inducing, at the midblastulae stage, mesoderm formation from animal pole cells destined to form ectodermal structures. This primordial role explains the wide variety of tissues, ranging from the central and peripheral nervous system to the vascular system, that are affected by FGF during the late embryonic, neonatal, and adult phases of development. PMID- 2199120 TI - Medical specialty credentialing in the United States. AB - Specialty boards serve the function of defining qualifications and issuing credentials to assure the public of the specialist's preparation and skill. Over the past 72 years, 23 such boards have been approved and now issue 31 different types of general specialty certificates and 57 types of subspecialty credentials. For 50 years, the American Board of Medical Specialties has encouraged a system of recertification to demonstrate that the certified specialist has maintained skill and has incorporated the new knowledge associated with advancing medical science. Presently, 17 of the 23 boards are committed to time-limited certificates requiring recertification every seven to ten years, and others are currently planning such a process. New methods of performance assessment are being used for recertification processes. In addition to recertification, the other major change in specialty credentialing is the number of subspecialty certificates sought and authorized. The numbers have increased dramatically during the past 20 years and reflect the advances in science as well as new styles of practice. As a consequence, some specialties are moving toward accreditation without certification to improve training, even if there is no authorized type of certification. Another consequence of subspecialty proliferation is concern about fragmentation of medical care and its effect on the costs of health care. PMID- 2199123 TI - Fifty years of the American Board of Orthopaedic Surgery. 1934. PMID- 2199122 TI - Rationale and protocol for postoperative anterior cruciate ligament rehabilitation. AB - A rehabilitation program for postoperative anterior cruciate ligament (ACL) reconstruction permits adequate tissue healing time and allows early protected muscular conditioning. The program is based on kinematic, biomechanical, and kinesiologic factors as they pertain to ACL function. The program is divided into five phases. The early phases, zero to 12 weeks, are intended to control translational forces across the ACL and to allow necessary time for ligament revascularization and soft-tissue healing. During this period, isometric and isotonic training of the hamstrings and quadriceps muscle groups in a restricted active arc of motion is permitted. Passive motion is encouraged, and progressive weight bearing is allowed. Conditioning of the upper body as well as the nonsurgical lower limb is stressed. During the advanced phases, 12-31 weeks, isotonic muscle training continues throughout a full range of motion. Greater strength, coordination, and endurance to achieve dynamic stability of the knee, preparing the patient for unrestricted activity, are stressed. Approximately 52 weeks of active rehabilitation after ACL reconstruction surgery are usually required to return to a preinjury level of function. PMID- 2199124 TI - Prostaglandin E2 levels in the membrane surrounding bulk and particulate polymethylmethacrylate in the rabbit tibia. A preliminary study. AB - Fourteen mature New Zealand white female rabbits were allocated into two groups. Group 1 received a bolus doughy Simplex polymethylmethacrylate (PMMA) cement injected into the proximal tibia through a drill hole. Group 2 received an equal volume of particulate PMMA cement powder. The operated but nonimplanted left tibiae served as controls. The animals were killed after four months. The membrane surrounding the implant area was harvested aseptically and grown in tissue culture. The supernatants were assayed for prostaglandin E2 (PGE2) via radioimmunoassay. Bulk cement specimens produced on average 12.39 +/- 4.11 ng PGE2 on the right experimental side and 12.29 +/- 3.56 ng PGE2 on the left control side (not statistically different). Cement powder specimens produced 8.82 +/- 1.64 ng PGE2 on the right experimental side, which was statistically different from 4.21 +/- 0.88 ng PGE2 produced on the left control side. The ratio of PGE2 values for the right divided by the left side and the arithmetic difference between right and left sides were significantly higher in the particle group compared with the bulk group. Small, undigestable cement particles may be phagocytosed by foreign-body giant cells and histiocytes and then extruded into the extracellular compartment, along with substances such as PGE2. PGE2 has been implicated as the biologic mechanism for stimulating the bone lysis associated with prosthetic loosening. PMID- 2199125 TI - Therapeutic drug monitoring in the neonate and paediatric age group. Problems and clinical pharmacokinetic implications. AB - Therapeutic drug monitoring should encompass not only serum concentration monitoring but also assessments of organ and clinical functions. This is especially important in children, in whom receptor drug concentration or sensitivity may be different from that seen in the adult population. Therapeutic end-points should be identified and serum drug concentrations adjusted to meet these goals. This is further complicated by the added impact of pharmacokinetic idiosyncrasies displayed by children, coupled with the routine pitfalls of therapeutic drug monitoring seen in any patient population. Neonates and infants present the additional challenge of having a set of mechanisms whose degree of maturation sometimes changes on a day-to-day basis with alarming rapidity. It is this phenomenon which makes the definition of pharmacokinetic parameters following a single dose so unreliable and potentially hazardous. Therapy should be based not only on the capacity of the infant to eliminate and respond to a particular agent, but also on the understanding of the dynamic changes that will occur on an ongoing maturational basis. A basic familiarity with the patient population under study is essential in obtaining relevant data for pharmacokinetic analysis. Special consideration in children should focus on potential problems with drug administration, drug absorption, metabolite patterns, changing drug disposition, idiosyncratic reactions, receptor sensitivity and chronopharmacokinetics. As with other patient populations, serum drug concentration monitoring is only a small part of the clinical scenario, the whole of which must be the basis for therapeutic decisions and pharmacodynamic titration. PMID- 2199126 TI - Influence of exercise on the pharmacokinetics of drugs. AB - Since many patients with a wide variety of diseases are nowadays stimulated to adopt a physically active lifestyle, the question of the influence of exercise on the pharmacokinetics of drugs has become more and more relevant. Because exercise influences a large number of physiological factors that also determine the pharmacokinetics of drugs, including haemodynamics, metabolism, pH, temperature and gastrointestinal function, it can be expected to have an effect on the pharmacokinetic parameters (absorption, distribution, elimination) of certain agents. However, only a very limited number of studies has been directed towards this issue, and only a very few drugs have been studied. Nevertheless, it is clear that exercise does influence the pharmacokinetics of certain drugs, although the magnitude and direction of the effects vary. This is not surprising in view of the widely differing physicochemical properties of drugs, the many possible--often opposing--effects of exercise on the parameters affecting drug pharmacokinetics and the different types of exercise performed. The chance of a clinically relevant effect of exercise on the pharmacokinetics of a particular drug is largest in those with a steep dose-response curve, a narrow therapeutic range, a need for continuity of therapeutic effectiveness and a relatively short half-life, in combination with intensive exercise of long duration. If untoward drug effects occur during or after exercise, a change in the pharmacokinetics of the drug related to the exercise should be seriously considered as a possible cause. PMID- 2199129 TI - Disease-induced variations in plasma protein levels. Implications for drug dosage regimens (Part I). AB - Many diseases appear to lead to a decrease of drug plasma binding due either to hypoalbuminaemia or to a modification of albumin structure. In other diseases, the binding of a drug may increase due to elevated concentrations of alpha 1-acid glycoprotein or lipoproteins. However that may be, the free fraction of a drug may vary in different pathologies. But an increase or decrease of the drug free fraction does not automatically mean an increase or decrease of the free drug concentration. Whatever the drug, a variation in the volume of distribution more or less proportional to the variation in the plasma free fraction can be expected. With respect to the clearance, the problem is much more complex and depends on the hepatic extraction ratio of drug. If the extraction is related to the free fraction (fu) of drug, a variation in fu will lead to a variation in the total drug concentration but no variation in the free drug concentration and no change in the pharmacological effect. If the extraction of a drug is dependent on hepatic flow, a variation in fu will lead to a change in the free drug concentration (with no change in the total drug concentration) and hence changes in the pharmacological effect. The aim of this article is to review the literature concerning disease-induced variations in plasma protein levels during the past 10 years. Finally, possible implications for drug dosage regimens are discussed generally from examples studies in the literature. PMID- 2199128 TI - Clinical pharmacokinetics of prednisone and prednisolone. AB - The growth of knowledge in the field of the pharmacokinetics of prednisolone/prednisone has been slow for several reasons. First, convenient and specific methods for measuring these steroids only became available with the development of high performance liquid chromatographic methods. Secondly, prednisolone is nonlinearly bound to transcortin and albumin: since the unbound concentrations of prednisolone are biologically relevant, it was necessary to determine the free fraction in each plasma sample. Thirdly, due to the short half life of prednisolone no steady-state is achieved, and therefore area under the concentration-time curve needed to be determined in all studies. Fourthly, prednisolone and prednisone are interconvertible and prednisolone is given intravenously as an ester prodrug, features which created controversies about the correct interpretation of pharmacokinetic results. Finally, the total body clearances of total and (to a lesser degree) of unbound prednisolone increase with increasing concentrations of prednisolone. Therefore, in order to compare pharmacokinetic results between different subjects, standardised doses had to be administered. The investigations performed so far have revealed that: (1) the dose-dependent pharmacokinetics partly explain the clinical observation that an alternate-day regimen with prednisone yields fewer biological effects; (2) the interconversion of prednisone into prednisolone is not a limiting factor, even in patients with severely impaired liver function; (3) hypoproteinaemia per se does not cause increased unbound concentrations of prednisolone in vivo; (4) patients with liver failure, renal failure or a renal transplant, subjects older than 65 years, women on estrogen-containing oral contraceptive steroids or subjects taking ketoconazole have increased unbound concentrations of prednisolone-whereas hyperthyroid patients, some patients with Crohn's disease, subjects taking microsomal liver enzyme-inducing agents or patients on intravenous prednisolone phthalate (instead of prednisolone phosphate) or on some brands of enteric coated prednisolone tablets have decreased concentrations of prednisolone. The biological relevance of the altered pharmacokinetics is supported in part by altered clinical effects and altered effects on cellular immunofunctions. PMID- 2199127 TI - Pharmacokinetic drug interactions with nonsteroidal anti-inflammatory drugs. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs. Drug interactions with this class of compounds are frequently reported and can be pharmacokinetic and/or pharmacodynamic in nature. The pharmacokinetic interactions can be divided into 3 classes: (1) drugs affecting the pharmacokinetics of an NSAID. (2) an NSAID interfering with the pharmacokinetics of another NSAID and (3) NSAIDs altering the pharmacokinetics of another drug. Although the pharmacokinetics of some NSAIDs may be significantly affected by the concurrent administration of certain other drugs (including other NSAIDs), this type of interaction only occasionally leads to serious complications. Concurrent administration of antacids or sucralfate may delay the rate of oral absorption of NSAIDs but generally has little effect on the extent. Use of antacids increases urinary pH, leading to increased renal excretion of unchanged salicylic acid and decreased plasma concentrations of this antirheumatic agent. The H2-receptor blocking agent cimetidine inhibits the oxidative metabolism of many concurrently administered drugs, including certain NSAIDs. Probenecid inhibits the renal secretion of drug glucuronides and this will lead to accumulation in plasma of those NSAIDs eliminated primarily by the formation of labile acyl glucuronides such as naproxen, ketoprofen, indomethacin, carprofen. Cholestyramine decreases the oral absorption of many concurrently administered drugs, including NSAIDs. It may also decrease plasma concentrations of those NSAIDs undergoing enterohepatic circulation (e.g. piroxicam, tenoxicam) by interrupting the enterohepatic cycle. Corticosteroids stimulate the clearance of salicylic acid, leading to low plasma salicylate concentrations. Plasma concentrations of many NSAIDs are significantly reduced when the NSAID is coadministered with aspirin. The clinical relevance of most of these interactions is not well established. However, in those cases where the interaction results in elevated plasma concentrations of the NSAID, special caution should be exercised to avoid excessive accumulation of the NSAID especially in elderly and/or very sick patients who may be more sensitive to the more serious gastroduodenal and renal side-effects of these agents. By virtue of their pharmacokinetic and pharmacodynamic properties, NSAIDs may significantly affect the disposition kinetics of a number of other drugs. They can displace other drugs from their plasma protein binding sites, inhibit their metabolism or interfere with their renal excretion. If the affected drug has a narrow therapeutic index, the interaction may be clinically significant. The pyrazole NSAIDs (phenylbutazone, oxyphenbutazone, azapropazone) inhibit the metabolism of many drugs such as the coumarin anticoagulants, oral antidiabetics and anticonvulsants such as phenytoin. Salicylates displace oral anticoagulants from their plasma protein binding sites.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2199131 TI - Serum concentrations and effects of (+/-)-nicardipine compared with nifedipine in a population of healthy subjects. AB - The dihydropyridine calcium antagonist (+/-)-nicardipine shares some of the pharmacologic properties of the dihydropyridine prototype nifedipine. To compare them, serum concentrations and cardiovascular effects of 10 mg nifedipine and 20 mg (+/-)-nicardipine were evaluated at 1, 2, and 3 hours after oral intake in a randomized, crossover, single-blind study involving 79 healthy volunteers. (+/-) Nicardipine serum concentrations were much lower than those of nifedipine, indicating a greater hepatic first-pass metabolism of (+/-)-nicardipine. There was a significant correlation between serum concentrations of both drugs. The frequency distributions of nifedipine and (+/-)-nicardipine AUC (0-3), heart rate increase, and mean arterial pressure decrease showed no bimodality. This does not confirm the proposed polymorphism of nifedipine oxidation. Concentration-effect plots indicate that (+/-)-nicardipine is more potent than nifedipine but shows comparable efficacy in blood pressure reduction. PMID- 2199132 TI - Population pharmacokinetics of zidovudine. The Veterans Administration Cooperative Studies Group. AB - The epidemic of human immunodeficiency virus infection has forced an unprecedented acceleration of drug development. The lack of effective therapy at present against many of the infectious complications of acquired immunodeficiency syndrome (AIDS) has forced the rapid clinical introduction of new agents. Population pharmacokinetic models are particularly attractive as a means of assessing drug disposition in cohorts different from those studied during necessarily abbreviated phase I trials. We have used the population pharmacokinetics model as implemented by the computer program NONMEM to study the distribution of zidovudine in a large number of patients who have AIDS-related complex and who are therefore at an earlier stage of immunosuppression than subjects in other studies. We confirm a clearance of drug identical to that seen by traditional methods but a larger volume of distribution than estimated previously in patients with AIDS. Possible reasons for this discrepancy and the use of this method in the development of antiretroviral therapy are discussed. PMID- 2199133 TI - Effects of the ACAT inhibitor CL 277,082 on cholesterol metabolism in humans. AB - A common pharmacologic approach to lowering elevated serum cholesterol levels has been to interfere with intestinal sterol absorption. Inhibitors of acyl coenzyme A: cholesterol acyltransferase (ACAT) should produce this effect. In this study, we examined the effects of CL 277,082, N-(2,4-difluorophenyl)-N-(4 neopentylbenzyl)-N-(n-heptyl)urea, an ACAT inhibitor, on cholesterol metabolism in humans. Eight healthy male volunteers were given a placebo for 14 days, followed by 750 mg/day CL 277,082 for 20 days in a single-blind, crossover design. Subjects were studied in a hospital research unit and were fed strictly controlled diets. Cholesterol absorption was measured by the dual isotope method during the final week of both the placebo and the drug phases. Sterol balance was also assessed during these two periods by measuring cholesterol intake, and fecal neutral and acidic sterol excretion rates. Plasma lipids and lipoproteins were measured at the end of each period. The drug was well tolerated and produced no detectable clinical or laboratory side effects. Cholesterol absorption, sterol excretion rates, and plasma lipoprotein levels were all unaffected by treatment. We conclude that CL 277,082 may not interfere with ACAT activity or cholesterol absorption in humans at the doses given under the conditions tested in this study. PMID- 2199134 TI - Peptide growth factors and wound healing. AB - An analysis of peptide growth factors and wound healing should not fail to give credit to its foundations in cancer research. Add the recent advances in peptide chemistry and molecular genetics that have permitted complete definitions and in vivo studies for the first time. The result is an enormous break-through in wound healing research. The potential for understanding and then using the growth factors to enhance healing in the aged or debilitated is incalculable. PMID- 2199135 TI - Immune aspects of wound repair. AB - During the past few years, it has become evident that the cellular immune system plays a major role in the regulation of various phases of wound healing. Although there is much to learn about the interaction of the immune system with the healing wound, the explosion of knowledge in the field of growth factors and of monokines and lymphokines has generated information that greatly increases our understanding of the wound healing phenomenon. This discussion of the cellular immune system is restricted to macrophages and T lymphocytes. PMID- 2199136 TI - Wound metabolism. AB - The science of wound healing is vital to all aspects of plastic surgery. Knowledge of wound metabolism is essential to a complete understanding of wound healing. Through various laboratory models, we have isolated and studied many of the parameters involved in tissue repair and metabolism. Our findings suggest that biochemical aspects of wound healing are directed by the metabolism of the cellular infiltrate in the wound. These findings help to explain the independent nature of the wound during its healing process ("biological priority"). PMID- 2199137 TI - Oxygen and wound healing. AB - Surgeons have been aware of the detrimental effect of ischemia and hypoxia on healing tissues. In order to assist repair in such circumstances, a variety of modalities including revascularization, flaps, and hyperbaric O2 have been developed. Although these are apparently successful from a clinical standpoint, only recently has experimental evidence demonstrated conclusively that oxygen is a controlling factor in wound repair. Furthermore, it is now clear that traditional expectations of repair can often be exceeded by increasing the partial pressure at which oxygen is supplied to wounds. PMID- 2199138 TI - Oxygen free radicals and wound healing. AB - Oxygen-dependent mechanisms for intracellular killing by leukocytes result in the generation of highly reactive oxygen metabolites. These are called oxygen radicals. The purpose of this article is to define the oxygen free radical and the methods by which it is generated as well as the mechanisms by which these radicals produce injury. Specifically, recent studies investigating the role of oxygen-derived free radicals in wound healing are reviewed. PMID- 2199139 TI - Wound healing alterations caused by infection. AB - The theoretical alterations of wound healing caused by infection apply to the clinical situation. The level of bacteria is clinically important as are the specific qualities of a given species. This latter consideration has not been as completely studied as have the quantitative aspects. However, as pharmacologic means of overcoming the wound healing alterations are sought, specific bacterial species' idiosyncrasies will have to be examined. This has already been identified for the beta-hemolytic streptococcus. That species has not adhered to the level of greater than 10(5) organisms to produce wound complications. It has been repeatedly shown to cause wound problems at a much lower inoculum. Similar information may become available for other organisms. However, it is clear that because wound healing in the clinical situation occurs in the presence of bacteria, it is important to be aware of potential alterations in the repair process that these bacteria can cause. PMID- 2199140 TI - Wound healing in diabetes mellitus. AB - Diabetes mellitus is a complex metabolic disorder whose components have several direct and indirect effects on the healing of wounds. This article examines how diabetes affects wound healing from the standpoint of alterations in the microvasculature, nerve function, and the immune system. PMID- 2199142 TI - Alterations in wound healing secondary to infusion injury. AB - Though uncommon, the occurrence of an extravasation of a tissue-toxic drug can be a very disconcerting event in the physician's practice. A wound specialist, such as a plastic surgeon, is frequently consulted. The author reviews the "state of the art" approach to these challenging wounds. PMID- 2199141 TI - Healing in the irradiated wound. AB - Poor or nonhealing of irradiated wounds has been attributed to progressive obliterative endarteritis. Permanently damaged fibroblasts may also play an important part in poor healing. Regardless of the cause, the key to management of irradiated skin is careful attention to prevent its breakdown and conservative, but adequate, treatment when wounds are minor. When wounds become larger and are painful, complete excision of the wound or ulcer is called for and coverage should be provided by a well-vascularized nonparasitic distant flap. PMID- 2199143 TI - Biologic skin substitutes. AB - The absence or loss of skin, because of the resulting drain of fluids and protein and because of the risk of invasive infection, requires wound closure with a skin substitute. Split-thickness skin graft is the gold standard for skin substitutes. Human cadaver allografts are the ideal temporary skin substitute, and their life can be prolonged by immunosuppression in the recipient. The potential for transmission of human immunodeficiency virus infections from these grafts limits their use. Epidermis can be replaced with tissue-cultured autogenous keratinocyte sheets. Several groups have used these grafts in patients successfully. Recent evidence indicates that the new epidermis directs the differentiation of the subjacent collagen tissue into an architecture resembling a papillary and reticular dermis. Several methods are being evaluated for the direct replacement of the dermis, including cadaver dermis, collagen-GAG matrices, and fibroblast impregnated collagen gels. Clinically useful advances in skin substitutes have been made in the last decade, and these advances will lead to the answer to the problem of missing skin. PMID- 2199144 TI - The healing of bone and cartilage. AB - Transplantation of bone should be preceded by careful assessment of the recipient site. The function of the transplanted bone as an interposition graft, as an onlay graft, or in restoration or construction of a missing part of the skeleton must be considered. Cortical bone provides superior mechanical strength and can be incorporated with plate fixation to span interposition defects. Membranous bone used as onlay grafts for augmentation of craniofacial skeletal contour has been shown to be superior to endochondral grafts in maintaining volume. The use of rigid fixation to secure onlay grafts may eliminate the differences in resorption seen with membranous versus endochondral bone. The vascularity and quality of soft tissue at the recipient site may necessitate the use of vascularized bone or composite free tissue transfer. The calvarium is the most popular donor site for bone grafts used in craniofacial skeletal procedures. This membranous bone undergoes less resorption and revascularizes faster than endochondral bone. Cranial bone has excellent mechanical strength due to its large cortical component. The calvarial donor site causes less discomfort to the patient compared with rib or iliac crest, and the scar is well hidden. Harvesting and shaping cranial bone require special expertise, and there is potential morbidity. In cartilage transplantation, the surgeon must take into account the properties of viscoelasticity, the intrinsic balanced system of forces, and immunologic privilege. Cartilage deformed by an external force will tend to return to its original shape unless the deformation is maintained for several months. Surgical carving produces changes in the balance of intrinsic tensile and expansile forces, causing distortion in cartilage shape. Distortion can be minimized by carving in balanced cross-section. Carved cartilage grafts should be used for special indications in rhinoplasty. Autogenous cartilage is the framework of choice in ear construction. Composite grafts incorporating cartilage have been used successfully in eyelid reconstruction. Fresh autogenous cartilage is preferable to preserved allogeneic sources, as the latter undergo eventual resorption because there are no viable chondrocytes to maintain the matrix. PMID- 2199145 TI - Wound healing in nerve. AB - The scope of this article is to provide a framework for the surgical approach to wound healing in nerve for the twenty-first century. The last decade has contributed information on the ultra-microscopic structure and function of nerve, the molecular events relating to neural regeneration, and the capabilities of nerve as a cell and nerve as tissue to respond to injury. PMID- 2199146 TI - Scientific basis for selecting staple and tape skin closures. AB - Use of tape and skin staples has many important clinical applications for surgical wounds. During the past two decades, our research program has identified the optimal performance parameters of these wound closure devices. On the basis of their unique performance characteristics, specific staplers and tapes are recommended for wound closure. The scientific basis for selecting staples and tapes for wound closure is based on their influences on the biology of wound repair and infection. PMID- 2199147 TI - Scientific basis for selecting surgical needles and needle holders for wound closure. AB - Standardized reproducible tests have been devised to determine surgical needle sharpness, resistance to bending, and ductility. Three comparable groups of reverse cutting edge needles were selected from different manufacturers for measurement of these needle performance parameters. This testing demonstrated that needle diameter, manufacturing process, needle material composition, cross sectional design, and the manufacturer were all important determinants of surgical needle performance. In addition, the biomechanics of curved surgical needle bending has been related to the clamping moment of surgical needle holders. This relationship identifies the surgical needle holder that can be used with surgical needles without deformation. The results of these studies provide a scientific basis for the selection of surgical needles and needle holders for use in surgery. PMID- 2199148 TI - Use of a nasal continuous positive airway pressure mask in the treatment of postoperative atelectasis in aortocoronary bypass surgery. AB - Pulmonary oxygen transfer, defined by PaO2/FIO2, and radiologic presence of atelectasis were measured pre-, intra-, and postoperatively to postoperative day 9 in elective cardiac aortocoronary bypass surgical patients, who were randomly allocated either to receive 18 h PEEP while on the ventilator followed by 12 h of nasal continuous positive airway pressure (nasal CPAP) or to be control subjects. The two groups were comparable in age, sex, forced expiratory volume in 1 sec (FEV1), the ratio of FEV1 over forced vital capacity (FVC), time on pump, units of blood transfused, New York Heart Association grading, and cardiac performance indices. The PaO2/FIO2 was significantly (p less than .05) better from half an hour after extubation until 24 h postextubation in the nasal CPAP group, but was decreased for the remainder of the study in both groups. Incidence of atelectasis/consolidation was not different in both groups during the study period. We conclude that nasal CPAP is well tolerated as a treatment of hypoxemia in the immediate postoperative period of aortocoronary bypass patients. CPAP does not change the course of postoperative atelectasis. PMID- 2199149 TI - Does continuous positive airway pressure compensate for loss of glottic function during tracheal intubation? AB - Adult patients with acute lung injury (ALI) exhibit increased PaO2 when receiving continuous positive airway pressure (CPAP). Some have increased PaO2 after extubation. To determine the role a competent glottis played in improving gas exchange, we anesthetized seven rabbits and inserted central venous and carotid artery catheters. After recovery from anesthesia, ALI was induced with oleic acid (0.08 ml/kg). Twenty-four hours later, the animals were sedated and placed in a sling. The pHa and blood gas tensions were measured. The animals were placed supine and were given inhalation anesthesia to facilitate tracheal intubation. A polyethylene catheter was placed slightly distal to the tracheal tube outlet to measure tracheal pressure (PT). Intubated rabbits were repositioned in the sling and were given either zero end-expiratory pressure (ZEEP) or 5 cm H2O CPAP, alternately. After the animals had breathed room air for 60 min, pHa and blood gas tensions were again measured, and PT was recorded. Animals were extubated, but the PT catheter was left in place. Data were collected again 60 min later, the catheter was removed, and the animals were returned to their cages. Forty eight hours after onset of ALI, the protocol was repeated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2199150 TI - Laboratory evaluation and use of the Engstrom metabolic computer in the clinical setting. AB - Laboratory evaluation and use of the Engstrom metabolic computer (EMC) in a clinical setting are described. The accuracy of the EMC was tested using an inert gas dilution technique. Mean errors in oxygen consumption (VO2) and CO2 production compared with predicted values were less than 2% of predicted, and generally less than 1%, but with an SD of less than or equal to 5.1%. At an FIO2 of greater than or equal to 0.7, the errors in VO2 were erratic and generally greater than 15%. The apparatus has the facility to assume an RQ in the calculation of VO2 and the errors in measured VO2 were less than 1% up to an FIO2 of 0.8. PMID- 2199151 TI - Usefulness of an antireflux valve in the intensive care unit. AB - The Keith Antireflux Valve (ARV) is a one-way valve placed on the sump port of a double-lumen NG tube. ARV use in critically injured patients significantly prevents reflux through the sump port and decreases the incidence of both patient gown and linen change and NG tube repositioning. There is no evidence to indicate that the ARV may lead to malfunction of the NG tube, aspiration, or gastric dilation. The cost savings in materials and nursing time are significant. PMID- 2199152 TI - Treatment of an infant with tracheobronchomalacia at home with a lightweight, high-humidity, continuous positive airway pressure system. PMID- 2199130 TI - Clinical pharmacokinetics of drugs used in the treatment of gastrointestinal diseases (Part II). AB - Part I of this article, which appeared in the previous issue of the Journal, covered the following agents: histamine H2-receptor antagonists (cimetidine, ranitidine, famotidine, nizatidine); muscarinic-M1-receptor antagonists (pirenzepine); proton pump inhibitors (omeprazole); site-protective agents (colloidal bismuth subcitrate, sucralfate); antacids and prostaglandin analogues; antiemetics and prokinetics (metoclopramide, domperidone, cisapride); and antispasmodics. In Part II, we consider the anti-inflammatory salicylates, nonspecific antidiarrhoeal agents, laxatives and cathartics. PMID- 2199153 TI - Cryoprotectant toxicity and cryoprotectant toxicity reduction: in search of molecular mechanisms. AB - Cryoprotectant toxicity is a fundamental obstacle to the full potential of artificial cryoprotection, yet it remains in general a poorly understood phenomenon. Unfortunately, most relevant biochemical studies to date have not met the basic criteria required for demonstrating mechanisms of toxicity. A model biochemical study of cryoprotectant toxicity was that of Baxter and Lathe, which demonstrated that alteration of a specific enzyme (fructose diphosphatase, or FDPase) was the cause of impaired glycolysis after treatment with and removal of dimethyl sulfoxide (D). FDPase alteration by D was reported to be preventable by the simultaneous presence of amides. This protection could be due to a "counteracting solute" effect similar to that employed by nature, but we find no meaningful correlation between the general protein stabilizing or destabilizing tendency of the cryoprotectant medium and its toxicity. Baxter and Lathe postulated that the effect of D arises from hydrogen bonding between D and the epsilon amino groups of surface lysine residues on FDPase, and it was found that molecules which resembled this group could block the alteration induced by D, presumably by competing with lysine residues for association with D. However, we find that the interaction between D and lysine in the presence of water is actually thermochemically repulsive, and that the presence of formamide does not affect the interaction between D and lysine, implying no useful complex formation between formamide and D. We were also unable to demonstrate that the blocking compounds consistently reduce toxicity when added to D rather than substituting for D, contrary to predictions based on complex formation between blocking compounds and D. In summary, it seems that present concepts of cryoprotectant toxicity are in need of serious revision. PMID- 2199154 TI - Developmental activities of the epidermal growth factor receptor. AB - EGF-Rs are encoded by a single gene which produces two main transcripts that are translated and processed into a single polypeptide chain. The membrane-inserted receptor kinase binds EGF or TGF-alpha at high and low affinities, but how these are related to the pleiotropic activities of the EGF-R is unknown. The widespread distribution of fetal EGF-Rs suggests that they have many functions during mammalian development. The stage- and cell type-specific expression of receptors in tissues such as the placenta, together with the localized production of EGF/TGF-alpha, suggests that fetal EGF-Rs have specific activities and roles. The proliferation of the fetal trophoblast and the maternal deciduum is likely to provide the location for a major and necessary role of TGF-alpha and EGF-Rs, which probably act by autocrine and paracrine means to establish the placenta as rapidly as possible. There is evidence that if placental EGF-Rs malfunction, the fetus is at a disadvantage. This could be partly due to poor placental growth and development, as well as a reduced ability of the placenta to perform a barrier function. The murine fertilized egg at preimplantation stages produces a number of growth factors, including TGF-alpha, but the significance of this is still uncertain. It is likely that several fetal and adult tissues produce low amounts of EGF/TGF-alpha for their self-maintenance. The precise roles for the putative EGF/TGF-alpha produced in the brain, kidney, tooth, and various head tissues are also obscure and will be subjects of close scrutiny in the future. PMID- 2199155 TI - Nerve growth factor and the issue of mitosis in the nervous system. PMID- 2199156 TI - Developmental roles for growth factor-regulated secreted proteins. PMID- 2199157 TI - Growth factor-regulated proteases and extracellular matrix remodeling during mammalian development. AB - Although specific details may vary from system to system, some general concepts have emerged from studies of the regulation of ECM components, proteases, and protease inhibitors by growth factors. Growth factors may be divided into those that enhance matrix synthesis and inhibit matrix degradation and those that stimulate protease production and result in a general degradation of ECM. These relationships are illustrated in Fig. 3. In general, growth factors such as EGF, PDGF, bFGF, and IL-1 induce genes for ECM-degrading proteinases and their activators (e.g., metalloproteinases and PAs). This concerted release of proteases results in the degradation of the many components of basement membranes or ECM. Other growth factors (e.g., the TGF-beta family) stimulate the synthesis of ECM structural proteins (e.g., collagens and fibronectin), elevate levels of inhibitors of proteases (e.g., TIMP and PAI-1), and repress expression of the matrix-degrading metalloproteinases and PA. The overall result is systems in which such a relationship seems very likely. Direct evidence should become available within the next few years now that the technology exists to correlate spatial and temporal expression of growth factors with expression of ECM associated proteases and inhibitors and to misregulate this expression in specific ways, for example, in transgenic mice. Future studies involving the use of model systems in which complex tissue interactions and organogenesis can be followed in culture should also provide the opportunity to examine cause-and effect relationships between growth factors and ECM-modulating proteins. PMID- 2199158 TI - The role of growth factors in embryonic induction in amphibians. PMID- 2199159 TI - Epidermal growth factor and transforming growth factor-alpha in the development of epithelial-mesenchymal organs of the mouse. AB - Taken together, there is a substantial amount of evidence that EGF-like growth factors have a physiological role in organ development and that the action of EGF or TGF-alpha in the development of epithelial-mesenchymal organs is associated with tissue interactions that guide morphogenesis and differentiation. The functions of growth factors in these interactions are not known at present, but they can be speculated in light of recent data. EGF and TGF-alpha might act as paracrine mediators of tissue interactions during organ development, as has been suggested for TGF-beta, which, together with fibroblast growth factor, acts as a morphogen to induce differentiation of embryonic tissue that is normally induced by tissue interactions (Kimelman and Kirschner, 1987). By in situ hybridization, TGF-beta mRNA was shown to be expressed by epithelial cells in many epithelial mesenchymal organs (Lehnert and Akhurst, 1988), whereas by immunolocalization the TGF-beta protein was found in the mesenchymal stroma (Heine et al., 1987). Although there have been some studies of the localization of EGF and the EGF-R in the embryo, which are discussed in Chapter 1 of this volume, there is a need for more detailed studies of the relative distribution of cells that synthesize the receptor and its ligand at various stages of organogenesis. The use of appropriate cDNA probes and the in situ hybridization technique will enable the localization of sites of EGF or TGF-alpha synthesis in relation to sites of receptor expression in developing organs and thus provide a deeper understanding of how EGF/TGF-alpha coordinates epithelial-mesenchymal interactions throughout development. PMID- 2199160 TI - Fibroblast growth factor and its involvement in developmental processes. PMID- 2199161 TI - The spontaneously diabetic BB rat: sites of the defects leading to autoimmunity and diabetes mellitus. A review. AB - In summary, our bone marrow chimeras studies suggest that there are two defects in the BB rat associated with diabetes and/or lymphopenia, one residing at the level of the bone marrow lymphoid stem cell and the other within the T-cell differentiative environment, apparently postthymic. Our neonatal thymus transplantation studies and the adult thymus transplantation studies of others suggest a third defect in the BB rat, within the thymus itself, but this defect appears not to be responsible for the development of either the diabetes or the T lymphocytopenia. Rather, the thymic defect appears to control, at least in part, the lymphocyte hyporesponsiveness characteristic of the diabetes-prone BB rat. The role of the RT6 T-cell differentiation antigen in the etiopathogenesis of diabetes in this animal model remains unclear. PMID- 2199162 TI - The role of class II molecules in development of insulin-dependent diabetes mellitus in mice, rats and humans. PMID- 2199163 TI - Major histocompatibility complex molecules and the beta cell: inferences from transgenic models. PMID- 2199164 TI - Immune pathogenesis of diabetes in the nonobese diabetic mouse: an overview. PMID- 2199165 TI - Autoantigen (64000-Mr) expression in coxsackievirus B4-induced experimental diabetes. PMID- 2199166 TI - Effects of rubella virus infection on islet function. PMID- 2199167 TI - Monoclonal (auto)antibodies in insulin-dependent diabetes mellitus. PMID- 2199168 TI - The genetics of insulin-dependent diabetes in the BB rat. AB - Very little is known about the genes involved in the pathogenesis of IDDM. One component is known to be linked to the major histocompatibility complex, but the other components are unknown. We know from the major animals models of IDDM, both the NOD mouse and the BB rat, that the disease is under multigenic control. However, due to the size and complexity of the mammalian genome as well as to the lack of useful clues, the location and identity of the other genes remains a mystery. This is compounded by the fact that well-characterized genetic markers are not available for all regions of the mammalian genome, and it is likely that at least some of the genes of interest are located in these regions. The testing of pedigrees for the linkage of RFLP with the genetic factors involved in IDDM promises to be the most effective means of mapping, and ultimately identifying, these genes. However, the number of genes which are theoretically necessary to test for linkage makes even this approach impractical. Here, we have described here how the amount of work and time can be significantly reduced by utilizing repetitive DNA sequences as probes for the linkage of random RFLPs to diabetes. With each screening, one can simultaneously test multiple unlinked loci in the genome. Preliminary results which show promising linkage to two of the genetic components have been presented, thereby supporting the usefulness of this approach. PMID- 2199169 TI - [Ultrasonic pulsed Doppler duplex system determination of portal hemodynamic changes in portal hypertension]. AB - Ultrasonic pulsed Doppler duplex system was used to observe the portal hemodynamic changes before and after shunting or nonshunting operations. The results of preoperative measurements revealed significant increases of blood flow volumes of portal and splenic veins in portal hypertension subjects, and a positive correlation was obtained in the subjects with portal hypertension. Postoperative results showed significant reduction of portal blood flow volume more after shunting than the nonshunting operations. The etiology of portal hypertension and the causes of portal hemodynamic changes due to operations were discussed. PMID- 2199171 TI - [Teratoma of the lung: report of 3 cases]. AB - In this paper, 20 cases of teratoma of the lung (3 cases were presented and 17 reviewed) were analyzed. There were 13 males and 7 females, the age ranging from 16-47 years. The primary symptoms were: cough (19 cases, 95%), blood sputum or hemoptysis (16 cases, 80%), chest pain (12 cases, 60%), fever (7 cases, 35%) and expectoration of hair (4 cases, 20%) etc. The histogenesis, diagnosis and treatment of the disease were discussed. PMID- 2199172 TI - [Cytological study of giant cell bone tumors: a 10-year summary]. PMID- 2199173 TI - [Orthopedic surgery of cerebral palsy]. PMID- 2199170 TI - [Clinical use of naproxen sodium in muscular skeletal disorders]. AB - Naproxen sodium is a new non-steroid antiinflammatory drug. This paper reported the results of clinical trial of the drug in 229 cases of orthopedic conditions. Among them, 103 cases were observed with double method. The rate of symptomatic relief was 81.3% (75 cases) for rheumatoid arthritis, 72.4% (29 cases) for osteoarthritis, 76.5% (34 cases) for herniations of lumbar discs and 93% (91 cases) for mild post-operative pain. The overall efficacy of the drug was 84.2% with 6.1% side effects, chiefly gastric reactions. PMID- 2199174 TI - Triple labeling with two-color immunofluorescence using one light source: a useful approach for the analysis of cells positive for one label and negative for the other two. AB - Many laboratories do not have access to a flow cytometer allowing three-color immunofluorescence analysis through the use of multiple light sources. In view of the usefulness of such analyses in the dissection of cell parameters, we describe an approach permitting the study of three labels by using one light source and the two-color immunofluorescence assay. It is useful for the enumeration of cell subpopulations positive for one label and negative for two or more others as well as for qualitative analysis concerning the expression of these labels. This approach is simple and rapid; it does not require additional material and technical steps other than that used in the two-color immunofluorescence assay. Briefly, it consists of the use of a label coupled to a dye (PE or FITC or instance) and two different labels coupled to the other dye. An argon ion laser, operating at 488 nm and 60 mW, excites both fluorescein and phycoerythrin conjugated antibodies. We provided a general example, using three hypothetical labels (X, Y, and Z), and four practical applications: CD3+CD4CD8- and CD8+CD16 CD3- peripheral blood lymphocytes, CD2+CD16-CD3- and CD56+CD16-CD3- peripheral blood, and decidual infiltrating lymphocytes. PMID- 2199175 TI - The clinical rationale of cardiac resuscitation. AB - After failure of external defibrillation, return of cardiac activity with spontaneous circulation is contingent on rapid and effective reversal of myocardial ischemia. Closed-chest cardiopulmonary resuscitation (CPR) evolved about 30 years ago and was almost universally implemented by both professional providers and lay bystanders because of its technical simplicity and noninvasiveness. However, there is growing concern since the limited hemodynamic efficacy of precordial compression accounts for a disappointingly low success rate; especially so if there is a delay of more than 3 minutes before resuscitation is started. There is also increasing concern with the lack of objective hemodynamic measurements currently available for the assessment and quantitation of the effectiveness of resuscitation efforts. Accordingly, the resuscitation procedure proceeds without confirmation that it increases systemic and myocardial blood flows to levels that would be likely to restore spontaneous circulation. Continuous monitoring of end-tidal carbon dioxide (PETCO2) now appears to be a practical measurement which provides a noninvasive quantitative indication of both systemic blood flow and coronary perfusion pressure. Consequently, PETCO2 predicts the likelihood of successful resuscitation and guides the operator who may modify the technique of precordial compression to improve systemic and myocardial perfusion. Among the large polypharmacy for cardiac resuscitation, only alpha-adrenergic agents (which increase coronary perfusion pressure) and especially epinephrine are of proven benefit. Neither buffer agents nor calcium salts appear to improve outcome except under unique conditions. To the contrary, there is increasing awareness of adverse effects of pharmacologic interventions such that they may hinder the return of viable myocardial and cerebral function. This has constrained the routine use of all drugs except for the use of alpha-adrenergic agonists. More invasive interventions by which blood flow is restored such as open-chest cardiac massage or extra-corporeal pump oxygenation (ECPO) are consistently more effective than conventional CPR. Experimentally, both methods promptly restore systemic and myocardial perfusion to viable levels and thereby increase the likelihood that spontaneous circulation is restored even after prolonged cardiac arrest or failure of conventional CPR. PMID- 2199176 TI - The cytochrome P450 I gene family of microsomal hemoproteins and their role in the metabolic activation of chemicals. PMID- 2199178 TI - [Diagnostic value of sonography of the spleen]. PMID- 2199179 TI - [Diagnosis by nuclear medicine in gastroenterology. An analysis from the viewpoint of gastroenterology]. PMID- 2199177 TI - Drug-protein conjugation and its immunological consequences. PMID- 2199180 TI - [Treatment of primary osteoporosis with calcium and salmon calcitonin]. AB - Fifty-nine consecutive patients (19 men, 40 women, mean age 60.8 [27-80] years) with primary osteoporosis were studied to see if there was any significant gain in bone mass after treatment with salmon calcitonin. All the patients were given 1 g calcium by mouth every morning. Group 1 (n = 20) received no other specific medication while group 2 (n = 19) were given 100 I.U. calcitonin subcutaneously every second evening and group 3 (n = 20) received the same dose every evening. The pain reported by the patients was subdivided into four severity grades, and analgesic consumption was recorded. In group 1 there was a nonsignificant decrease in pain, but in groups 2 and 3 there was a highly significant diminution in pain (P less than 0.005) and in analgesic intake (P less than 0.01). Measurements of bone density carried out by photon absorption at the end of 12 months showed a 5.5% increase in the distal radius in group 2 (P = 0.0001) and a 7.1% increase in group 3 (P = 0.0001), while in group 1 mineral content had decreased by 4.3% (nonsignificant). These results show that a significant gain in bone mass can be achieved by administration of calcitonin, either daily or on alternate days. The incidence of extravertebral fractures and of new or progressive vertebral deformity tended to be lower in groups 2 and 3 than in group 1. PMID- 2199181 TI - [Pathophysiology and symptomatology of an acute glaucoma attack]. PMID- 2199182 TI - [Treatment of an acute glaucoma attack]. PMID- 2199183 TI - [What is dispensable in the diagnosis of coronary heart disease?]. PMID- 2199184 TI - Nocardiosis of the upper aerodigestive tract. AB - Nocardia asteroides is the major cause of nocardiosis in the respiratory tract. The primary site of infection is the lung, with the upper aerodigestive tract being a rare region for localized disease to occur. We describe a case of a nocardial vallecular cyst and discuss the diagnosis and management of this unusual infection. PMID- 2199185 TI - [Increase in the level of polypeptide growth factors and their receptors in induced carcinogenesis and regeneration of the intestinal mucosa in rats]. AB - It has been established for the first time that in extracts of the regenerating and preneoplastic (4 months after the beginning of carcinogen introduction) intestine as well as in the peritumor tissue the content of EPR-similar polypeptides and insulin raises, whereas in tumours it remains not high. Proteins with molecular weight greater than 120 kD able to compete with 125I-EPR for the binding with the receptors of EPR and being, evidently, the precursors of EPP are found in case of carcinogenesis. Besides, the content of insulin receptors rises, this process being most typical of the large intestine. PMID- 2199186 TI - [Characteristics of genotoxic and carcinogenic action of metals]. AB - The data on carcinogenic activity of certain metals and their compounds to humans and experimental animals are reviewed. Cellular uptake and intracellular distribution of metal compounds, metal-induced genotoxicity in different short term tests are described. Specific lesions of DNA produced by carcinogenic metals, the influence of metal ions on the cell growth, DNA replication and DNA repair involved in mutagenesis and oncogenesis are under discussion. Mechanisms of metal carcinogenesis are studied to a less extent as compared with organic carcinogenesis. PMID- 2199187 TI - [Tissue specificity of monoclonal antibodies to cells of human pulmonary adenocarcinoma]. AB - Immunohistological localization of antigens revealed by 5 MoAbs to human lung adenocarcinoma cell line was studied by indirect immunoperoxidase technique. One of the MoAbs--A2F4--showed a relative specificity to epithelial tissues having a glandular differentiation. Except approximately 50% of normal cells of lungs and those of pulmonary tumours (mostly adenocarcinomas) they reacted with some other normal (stomach, oesophagus, breast) and tumoral (gastric, mammary and colonic) tissue cells. Other four MoAbs reacted with the much larger number of cells including some nonepithelial (granulocytes and histiocytes) ones. PMID- 2199188 TI - [Immunocytochemical detection of antigen associated with squamous cell cancer of the cervix uteri in women]. AB - Cervical preparations from 89 women were studied for antigen associated with squamous-cell cervical cancer (SCCC) by the indirect immunofluorescence method. The antigen was revealed specifically in 77.8% of samples of SCCC (stages Ib, II and III) in 64.3% of samples of cancer (in situ and stage Ia) in 55.5% of samples of displasia (stages II and III) and in 17.2% of samples from tumours of other organs. In samples of 9 healthy women the antigen was not revealed. Thus, the detection of antigen associated with SCCC may be useful in elaboration of adjuvant diagnostic and prognostic tests. PMID- 2199189 TI - [Expert systems in oncology: concepts, problems, perspectives]. AB - The architecture and fields of application of the expert systems in oncology are described. These systems allow systematization, developing and realizing the approximate knowledge, heuristics and algorithms of the expert-oncologists by the computer systems for solution of optimization problems of diagnosis and treatment of cancer patients. Principles of the functioning of expert systems are considered through the examples of solutions of concrete problems in oncology. Intellectual possibilities of the man-machine interaction under clinical conditions are discussed. The vistas of technological development of expert systems in oncology are evaluated. PMID- 2199190 TI - Regulation of intracellular Ca2+. PMID- 2199191 TI - Ethanol metabolism and alcoholic liver disease. PMID- 2199192 TI - Biochemistry and neurochemistry in the 1800s: their origins in comparative animal chemistry. PMID- 2199193 TI - Metabolic heterogeneity of liver parenchymal cells. PMID- 2199194 TI - Translational dynamics. Interactions between the translational factors, tRNA and ribosomes during eukaryotic protein synthesis. PMID- 2199196 TI - Two-dimensional NMR studies on des-pentapeptide-insulin. Proton resonance assignments and secondary structure analysis. AB - The shortened analogue of insulin, des-(B26-B30)-pentapeptide insulin, has been characterized by two-dimensional 1H NMR. The 1H resonance assignments and the secondary structure in water solution are discussed The results indicate that the secondary structure in solution is very similar to that reported for the crystalline state. A high flexibility of both A and B chains is observed. Of the two conformations seen in the 2-Zn insulin crystals and indicated as molecules 1 and 2 (Chinese nomenclature), the structure of the analogue is more similar to that of molecule 1. PMID- 2199195 TI - Valyl-tRNA synthetase from yeast. Discrimination between 20 amino acids in aminoacylation of tRNA(Val)-C-C-A and tRNA(Val)-C-C-A(3'NH2). AB - For discrimination between valine and the 19 naturally occurring noncognate amino acids, as well as between valine and 2-amino-isobutyric acid by valyl-tRNA synthetase from baker's yeast, discrimination factors (D) have been determined from kcat and Km values in aminoacylation of tRNA(Val)-C-C-A. The lowest values were found for Trp, Ser, Cys, Lys, Met and Thr (D = 90-870), showing that valine is 90-870 times more frequently attached to tRNA(Val)-C-C-A than the noncognate amino acids at the same amino acid concentrations. The other amino acids exhibit D values between 1,100 and 6200. Generally, valyl-tRNA synthetase is considerably less specific than isoleucyl-tRNA synthetase, but this may be partly compensated in the cell by valine concentrations higher than those of noncognate acids. In aminoacylation of tRNA(Val)-C-C-A(3'NH2) discrimination factors D1 are in the range of 40-1260. From D1 values and AMP formation stoichiometry, pretransfer proof-reading factors pi 1 were determined: post-transfer proof-reading factors II 2 were determined from D values and AMP formation stoichiometry in acylation of tRNA(Val)-C-C-A. II 1 values (7-168) show that pretransfer proof-reading is the main correction step, post-transfer proof-reading (II 2 approximately 1-7) is less effective and in some cases negligible. Initial discrimination factors were calculated from discrimination and proof-reading factors according to a two-step binding process. These factors, due to different Gibbs free energies of binding can be related to hydrophobic interaction forces, and a hypothetical 'stopper' model of the amino-acid-binding site is discussed. PMID- 2199197 TI - Solution NMR studies of colicin E1 C-terminal thermolytic peptide. Structural comparison with colicin A and the effects of pH changes. AB - The aqueous solution structure of the C-terminal thermolytic peptide of colicin E1 has been investigated using both one- and two-dimensional NMR techniques. The NMR data are consistent with a fold for the peptide very similar to that reported for the colicin A C-terminal peptide in the crystalline state, although some differences have been noted. The one-dimensional NMR spectrum of the peptide has been used to follow changes in both the structure and dynamics of the peptide on changing pH. The in vitro functionally competent form of the peptide (present in solution only below pH 6) does not differ in structure significantly from the higher pH form. However, small local conformational changes are observed together with an increase in mobility in some of the more hydrophilic regions. This suggests that the effect of lower pH is to change the ease with which the major conformational changes during insertion into a membrane can occur. PMID- 2199198 TI - Investigation into the fluidity of lipopolysaccharide and free lipid A membrane systems by Fourier-transform infrared spectroscopy and differential scanning calorimetry. AB - The phase behaviour, particularly the fluidity within each phase state and the transitions between them, of lipopolysaccharides and of their lipid moiety, free lipid A, of various species of Gram-negative bacteria, especially of Salmonella minnesota and Escherichia coli, has been investigated by applying mainly Fourier transform infrared spectroscopy and differential scanning calorimetry. For enterobacterial strains, the transition temperatures of the gel----liquid crystalline (beta----alpha) phase transition of the hydrocarbon chains in dependence on the length of the sugar moiety are highest for free lipids A (around 45 degrees C) and lowest for deep rough mutant lipopolysaccharides (around 30 degrees C). Evaluating certain infrared active vibration bands of the hydrocarbon moiety, mainly the symmetric stretching vibration of the methylene groups around 2850 cm-1, it was found that, in the gel state, the acyl chains of lipopolysaccharides and free lipid A have a higher fluidity as compared with saturated and the same fluidity as compared with unsaturated phospholipids. This 'partial fluidization' of lipopolysaccharide below the transition temperature correlates with its reduced enthalpy change at that temperature compared to phospholipids with the same chain length. The fluidity depends strongly on ambient conditions, i.e. on the Mg2+ and H+ content: higher Mg2+ concentrations and low pH values make the acyl chains of free lipid A and lipopolysaccharide preparations significantly more rigid and also partially increase the transition temperature. The influence of Mg2+ is highest for free lipid A and decreases with increasing length of the sugar side chain within the lipopolysaccharide molecules, whereas the effect of a low pH is similar for all preparations. At basic pH, a fluidization of the lipopolysaccharide and lipid A acyl chains and a decrease in transition temperature take place. Free lipid A and all investigated rough mutant lipopolysaccharides exhibit an extremely strong lyotropic behaviour in the beta----alpha melting enthalpy but not in the value of the transition temperature. The phase transition is distinctly expressed only at water concentrations higher than 50-60%. A further increase of the water content still leads to an increase in the phase-transition enthalpy, particularly for lipopolysaccharides with a more complete sugar moiety. The fluidity of the hydrocarbon chains is shown to be an important parameter with respect to the expression of biological activities.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2199200 TI - Methylprednisolone in high doses gives different effects on the early and the late part of complement. AB - The effects of methylprednisolone (MP) on endotoxin-induced activation of complement were studied in citrated pool plasma. Complement activation was tested in two immunoassays: one evaluating C3 activation fragments (C3act) and the other the terminal complement complex (TCC). These components are indicators of initial and terminal complement activation, respectively. Plasma samples were obtained at 1, 2, 4 and 6 h of incubation. Plasma containing endotoxin (2.10(9) ng/l) without MP revealed a marked increase of both C3act and TCC after 1 h. MP in high doses (10 mg/ml) gave an additive effect on activation of the initial part of the complement cascade compared to test plasma containing only endotoxin. In contrast, endotoxin-induced activation of the terminal part of the complement cascade was inhibited by the same dose of MP. The influence of lower doses of MP (0.1 and 1 mg/ml) on endotoxin-induced activation of complement was insignificant. Interestingly, MP without endotoxin induced activation of the initial part of complement. In test plasmas containing 5 and 10 mg/ml of MP (without endotoxin) marked increases of C3act values were seen. Despite this obvious activation of the early part of complement, only insignificant changes were found in TCC values. Test plasmas containing 0.1 and 1 mg/ml of MP revealed only minor changes in both C3act and TCC. In conclusion, the present study shows that high doses of MP activate the initial part of complement and that the endotoxin-induced activation of this cascade system was facilitated by MP. The terminal part of complement was, on the other hand, inhibited by high doses of MP. PMID- 2199201 TI - A specific fluorescent dye for ex situ staining of vital islets of Langerhans: neutral red. AB - We present a new technique for specific ex situ fluorescent staining of islets of Langerhans with neutral red. Depending on the concentration of neutral red (1 microgram/ml), this technique allows the differentiation between exocrine and endocrine pancreatic tissue, according to differences in fluorescence intensity. Pancreatic islets can be stained not only in situ, but in particular ex situ after pancreas digestion. Since intravital staining of the pancreas in situ with neutral red is not applicable in human transplantation, the staining procedure ex situ may be a useful tool for islet purification by particle sorting, using a fluorescent-light-activated system; thus, a sufficient mass of purified islets for free transplantation may be isolated. PMID- 2199199 TI - Adenomatoid tumors of the uterus. AB - The Adenomatoid Tumour is a rare benign neoplasm of the male and female genital tract. In the female it is seen with equal frequency in the uterus and the Fallopian tubes. In rare cases it is described in the ovarian and paraovarian connective tissue. In the uterus, AT is usually located in the cornual region, and its size usually varies between 0.5 and 2.0 cm in at its greatest dimension. The histogenesis of the AT is still a controversial subject, but the growing body of evidence now seems to favour a mesothelial origin. There is a frequent association between AT and leiomyomas in the uterus, with a variation between 56% and 80%. The treatment of the AT is simple excision of the tumour, if the uterus is not going to be removed for other reasons. Follow-up examinations of patients, who have undergone surgery for an AT have never, even over a period of up to 22 years, revealed recurrences and "malignant degeneration" is extremely rare. PMID- 2199202 TI - The effects of ingestion time of gliclazide in relationship to meals on plasma glucose, insulin and C-peptide levels. AB - The effect of altering the timing of gliclazide administration in relation to a meal was studied in ten type 2 (non-insulin dependent) chronically treated diabetics. Gliclazide was given 30 min before, at the start of and 30 min after breakfast or omitted altogether. Plasma gliclazide was present at greater than 2 mg/l throughout the study periods. Administration at 30 min after the meal significantly delayed the time to peak for plasma gliclazide. No significant difference was noted in plasma glucose, insulin or c-peptide patterns with any protocol. It is concluded that, in clinical practice, with chronically treated diabetics the timing of gliclazide ingestion in relation to meals is not critical. PMID- 2199203 TI - Effect of posture on total phenytoin plasma concentration. PMID- 2199204 TI - Thrombopoiesis-stimulating factor: its effects on megakaryocyte colony formation in vitro and its relation to human granulocyte-macrophage colony-stimulating factor. AB - The effects of thrombopoiesis-stimulating factor (TSF) on human marrow megakaryocyte colony formation in vitro were studied by the plasma clot method. TSF was found to stimulate megakaryocyte as well as granulocyte-macrophage colony formation in vitro at optimal concentrations of 200-300 pg/ml of medium containing 2.5% horse serum. This colony-stimulating effect of TSF was not affected by polyclonal antibodies to human (h) interleukin 3 (IL-3) or to granulocyte colony-stimulating factor (G-CSF) but was neutralized by monoclonal or polyclonal antibodies to human granulocyte-macrophage colony-stimulating factor (hGM-CSF). In order to differentiate among cross-reactivity between TSF and hGM-CSF, induction of colony growth via release of GM-CSF, and presence of hGM-CSF in TSF preparations, TSF was tested on murine marrow cells, which are not responsive to hGM-CSF. TSF induced growth of murine megakaryocyte colony-forming units (CFU-MK) and granulocyte-macrophage colony-forming units (CFU-GM) in vitro with a dose response similar to that observed on human marrow cells; however, this effect could not be neutralized by antibodies to either human or murine GM CSF. Using a double-antibody enzyme-linked immunosorbent assay, TSF preparations were found to contain 36 +/- 4 U of hGM-CSF per picogram of TSF protein. These findings indicate that hGM-CSF is responsible for the megakaryocyte colony promoting effects of TSF on human marrow cells in vitro. PMID- 2199205 TI - Thrombopoietin derived from human embryonic kidney cells stimulates an increase in DNA content of murine megakaryocytes in vivo. AB - A thrombocytopoiesis-stimulating factor (TSF or thrombopoietin) is known to increase the size and number of mouse bone marrow megakaryocytes, to increase the proportion of megakaryocytes in endomitosis, and to increase the number of small acetylcholinesterase-positive cells. Megakaryocyte ploidy values have not previously been measured in mice treated with TSF from human embryonic kidney (HEK) cells. Therefore, in the present study C3H mice were injected with approximately 4 U of step II TSF; platelet production indices and megakaryocyte ploidy values were measured 1-5 days after treatment. For controls, other mice were injected with saline, human serum albumin (HSA), normal rabbit serum (NRS), or rabbit anti-mouse platelet serum (RAMPS). Platelet counts, platelet sizes, and percent 35S incorporation into platelets were measured using standard techniques. For measurement of megakaryocyte DNA content, bone marrow cells were collected into CATCH medium and incubated with RAMPS, followed by labeling with a saturating concentration of fluorescein-conjugated goat anti-rabbit immunoglobulin F(ab')2 fragment. After washing, the cells were resuspended in propidium iodide, and DNA content was measured by flow cytometry. When compared to suitable control values, the results showed that TSF caused a significant (p less than 0.025) increase in platelet counts of treated mice by 3 days; both TSF and RAMPS caused significant (p less than 0.0005) increases in platelet sizes and percent 35S incorporation into platelets of mice at 2 and 3 days after treatment. The most frequent polyploid DNA class of megakaryocytes from untreated C3H mice was 32N, confirming our previous observation. Both TSF and RAMPS caused significant (p less than 0.0005) increases in the average polyploid megakaryocyte DNA content, with peak values on days 2 and 3. These data show that TSF administered in vivo significantly increases DNA content of mouse bone marrow megakaryocytes. PMID- 2199206 TI - Mechanisms of hyperinflation in asthma. AB - We studied 11 mild asthmatics to verify whether the mechanisms of hyperinflation in asthma could be inhibited or overcome by passively changing lung volumes. On day 1, we induced a fall in forced expiratory volume in one second (FEV1) of 30 60% by methacholine inhalation and measured the resulting increase in FRC (delta FRC). The delta FRC was 729 +/- 378 ml (mean +/- SD). On day 2, with the subject supine in an iron lung, we measured oesophageal (Poes), gastric (Pgas) and transdiaphragmatic (Pdi) pressures, and changes in functional residual capacity (FRC) (delta V) induced by extrathoracic pressures from -20 to +20 cmH2O before and after bronchoprovocation. With positive pressures, the FRC decreased and reached a plateau at 10 cmH2O pressure or higher. This plateau was at a mean FRC of 839 ml higher after the bronchoprovocation than before. Pdi at FRC varied in the same direction as the extrathoracic pressure and was not modified by the bronchospasm. Peak inspiratory Pdi, without pressure applied in the iron lung, increased from 13.6 +/- 5.4 to 28.1 +/- 13.5 cmH2O after methacholine; extrathoracic pressure of -20 cmH2O decreased this latter value to 15.4 +/- 7.3 cmH2O (p less than 0.01). The increased lung volume and the displaced chest wall recoil curve after provocation were not inhibited by positive or negative extrathoracic pressures. Our data show that the mechanisms of hyperinflation are not eliminated or overcome by passively changing lung volumes and support the hypothesis that persisting activity of inspiratory muscles other than the diaphragm during expiration and perhaps a prolonged expiratory time constant are responsible for hyperinflation in asthma. PMID- 2199207 TI - Comparative effects of volume history on bronchoconstriction induced by hyperventilation and methacholine in asthmatic subjects. AB - The aim of this study was to find out if bronchodilatation following deep inspiration can be induced by the inhalation of a "natural" stimulus (hyperventilation of cold dry air), and if the effect is similar to that induced by methacholine. After baseline assessment of lung resistance (RL), 10 asthmatic subjects were asked to inhale cold dry air for 3 min. RL was monitored continuously for 3-4 min, at which time subjects were asked to take a fast deep inspiration. After recovery, the manoeuvre was repeated and RL was reassessed. The manoeuvre was then repeated a third time. After functional recovery, progressive doses of methacholine were inhaled until the increase in RL was comparable to that obtained after hyperventilation (56 +/- 16% and 65 +/- 24%, respectively, mean +/- SD, NS). The same deep inspiration manoeuvre was repeated three times with recovery as after hyperventilation of cold dry air. Maximum changes in RL were not significantly different after each of the three manoeuvres for either type of bronchoconstriction. The mean fall in RL was 14.2 +/- 9.9% after hyperventilation and 16.4 +/- 10.5% after methacholine. There was a satisfactory correlation (r = 0.80, p less than 0.01) between the bronchodilatation after deep inspiration for both types of stimuli. We conclude that the bronchodilator effect of deep inspiration is no different using either a pharmacological stimulus (methacholine) or a "natural" stimulus (hyperventilation of unconditioned air). These results show that assessing the response to hyperventilation with manoeuvres requiring deep inspiration, forced expiratory volume in one second (FEV1) may alter airway tone in a way similar to pharmacological stimuli. PMID- 2199208 TI - Fibroblast-alveolar cell interactions in sarcoidosis and idiopathic pulmonary fibrosis: evidence for stimulatory and inhibitory cytokine production by alveolar cells. AB - To better understand how the activity of inflammatory cells collected by bronchoalveolar lavage (BAL) could affect the outcome of granulomatous and fibrotic pulmonary diseases, we studied secretory products and messenger ribonucleic acid (mRNA) expression for certain cytokines of BAL cells in 10 controls, 14 patients with interstitial pulmonary fibrosis (IPF) and 22 patients with sarcoidosis. We assayed the activity of 48 h conditioned media for: 1) their biological action on fibroblast proliferation and prostaglandin E2 (PGE2), collagenase and collagen production by fibroblasts; 2) TNF alpha levels by bioassay and radioimmunoassay; 3) interleukin 1 (IL-1) alpha and beta and beta levels by solid phase enzyme immunoassay (EIA); 4) tumor necrosis factor (TNF) and IL-1 inhibitory activity. We also measured, in freshly isolated BAL cells: 1) mRNA levels for IL-1 alpha and beta and TNF alpha; 2) cell-associated IL-1 alpha and beta by EIA. The only difference found in the assessment of the biological activity of BAL cells conditioned medium was an increase in fibroblast proliferation in sarcoidosis vs IPF patients. The IL-1 alpha and beta, and TNF alpha contents of conditioned media were similar in the three groups. Inhibitory activity against IL-1 and TNF alpha was found in a few patients. Further analysis revealed two peaks of inhibitory activity against IL-1 (20-25 kD and 35-40 kD), as well as a distinct TNF alpha inhibitory activity which could be retained on a TNF alpha-binding affinity column. No mRNA expression for TNF alpha was found in freshly isolated BAL cells, whereas very variable levels of IL-1 alpha and beta mRNA levels were detected in the three groups. Because of these variable results of differences in functional state between freshly isolated and cultured BAL cells, and of the presence of inhibitory substances against IL-1 and TNF alpha, it is unlikely that the development of fibrosis could be ascribed to a single disorder or abnormality. PMID- 2199209 TI - Inhibition of adenosine 5'-monophosphate- and methacholine-induced bronchoconstriction in asthma by inhaled frusemide. AB - Recent studies have shown that inhaled frusemide exerts a protective effect against various bronchoconstrictor stimuli in asthma including exercise, fog and allergen. Since mast cell activation seems to be a component of bronchoconstriction by these stimuli it is possible that inhibition of mediator release accounts for some or all of the inhibitory effects of frusemide in asthma. Since inhaled adenosine 5'-monophosphate (AMP) is another stimulus that produces bronchoconstriction by augmenting mast cell mediator release, we have investigated the ability of this drug to antagonise the airway effects of inhaled AMP and methacholine in a randomized, placebo-controlled, double-blind study of 12 asthmatic subjects. Inhaled frusemide (approximately 28 mg) administered 5 min prior to challenge increased the provocation concentration of inhaled AMP and methacholine required to reduce forced expiratory volume in one second (FEV) by 20% from baseline from 30 to 96 mg.ml-1 (p less than 0.01) and from 1.1 to 1.8 mg.ml-1 (p less than 0.01), respectively. The protection that frusemide afforded against AMP was significantly greater than that against methacholine (p less than 0.05). These data suggest that inhaled frusemide may serve as a functional antagonist against a smooth muscle spasmogen, such as methacholine, possibly by augmenting prostanoid generation. Its more potent activity against AMP and other bronchoconstrictor stimuli, that are considered to involve mast cell mediators, suggests an additional action on mast cell functions possibly at the level of the Ca++/Mg(++)-ATPase. PMID- 2199210 TI - Pharmacokinetics of antibiotics in the lungs. AB - This paper reviews current knowledge on the relationship between local penetration or antibiotics and therapeutic efficacy in pulmonary and bronchial infections. The antimicrobial drug concentration at the site of infection is supposedly determinative for the efficacy of the antibiotic treatment but the number of studies in respiratory infections supporting this hypothesis is limited. The mechanisms responsible for the pulmonary deposition or orally or systemically administered antibiotics include passive diffusion, active transport, bulk flow and permeation. The penetration of antimicrobial drugs into the respiratory tract is influenced by both host-related factors, such as inflammation or mechanical injury, and drug-related factors, such as molecular weight. In addition, local bio-inactivation can occur. The final bioactive antibiotic concentration at the site of the respiratory infection is, therefore, the result or a very complex dynamic process. Different sampling and measuring methods have been used for the assessment of antibiotic concentrations at the site of respiratory infections. Concentrations in sputum, bronchial secretions and biopsy specimens have been correlated with serum concentrations and clinical outcome. Bronchoalveolar lavage could be a promising technique for evaluating antibiotic drug concentrations in alveolar lining fluid. For many antibiotics, data concerning penetration and pharmacokinetic behaviour in the respiratory tract are lacking. PMID- 2199212 TI - Neural cell adhesion molecule (N-CAM) in fetal and mature human heart. AB - Using Northern blot analysis and immunoblotting techniques we report for the first time, that the neural cell adhesion molecule, N-CAM, is expressed in human heart. We found several different N-CAM transcripts in human fetal (13-17 weeks gestation) and mature heart (left ventricle from a 5-year-old child). Northern blotting showed that a 5.2 kb transcript was the most abundant and progressively increased with age, both in fetal and mature heart. These transcripts may correspond with the different protein isoforms shown by immunoblotting. We also confirmed the presence of N-CAM in fetal and mature myocytes by immunohistochemical techniques, using a monoclonal antibody to human N-CAM. Results demonstrated that N-CAM is mainly confined to the myocyte cell surface. PMID- 2199211 TI - The airways effects of inhaled chlorbutol in asthmatic subjects. AB - Chlorbutol is an antibacterial and antifungal agent incorporated in terbutaline (Bricanyl) nebulizer solution. Ten stable atopic asthmatic subjects undertook bronchial challenge testing, according to a double-blind protocol. Patients inhaled doubling concentrations of either methacholine (0.13-4.0 mg.ml-1) or chlorbutol (0.16-5.0 mg.ml-1) for 2 min until the forced expiratory volume in one second (FEV1) had fallen by 20% from baseline. If this had not occurred following the administration of the final concentration, then this highest concentration was repeated for 4 min. The nine subjects completing the study had a geometric mean provocation concentration producing a 20% fall from baseline FEV1 (PC20) methacholine of 0.16 mg.ml-1 (range less than 0.125-0.475 mg.ml-1). After inhalation of 2.5 mg.ml-1 chlorbutol one subject experienced a fall in FEV1 greater than 20%. In the remaining eight subjects, inhalation of chlorbutol did not affect airway calibre. We conclude that chlorbutol, in the concentration present in Bricanyl nebulizer solution, has no clinically significant effect on airway calibre. PMID- 2199213 TI - Selective solubilization of chlorosome proteins in Chloroflexus aurantiacus. AB - Proteins were solubilized selectively from chlorosomes of Chloroflexus aurantiacus by electrophoretic gel filtration according to Griebenow et al. Whereas the 11 kDa and 18 kDa proteins were extracted almost completely, the remaining modified chlorosomes contained high amounts of pigment and c-protein. It was concluded that the c-protein in contradiction to the publication by Griebenow et al. is indeed localized in the interior of Chloroflexus chlorosomes. PMID- 2199214 TI - Restoration of light induced photosystem II inhibition without de novo protein synthesis. AB - Illumination of isolated spinach thylakoid membranes under anaerobic conditions gave rise to severe inhibition of photosystem II electron transport but did not result in D1-protein degradation. When these photoinhibited thylakoids were incubated in total darkness the photosystem II activity could be fully restored in vitro in a process that required 1-2 h for completion. PMID- 2199215 TI - Interleukin-1 beta inhibits glucokinase activity in clonal HIT-T15 beta-cells. AB - Interleukin-1 beta (IL-1 beta) has been implicated in the pathogenesis of insulin dependent diabetes mellitus. In the present study we have investigated the effects of IL-1 beta on glucose metabolism in clonal HIT-T15 beta cells. In the short-term (1 h), 25 U/ml IL-1 beta significantly increased the rates of insulin release and glucose utilisation, but not glucose oxidation. In contrast, after 48 h, IL-1 beta inhibited insulin release and glucose utilisation and oxidation. By assaying enzymes (hexokinase, glucokinase, pyruvate dehydrogenase, glucose 6 phosphatase) and nucleotides (ATP, ADP) associated with the regulation of glycolysis and glucose oxidation, we conclude that the inhibitory effects of IL-1 beta may be due to impaired glucokinase activity. PMID- 2199216 TI - Pressure-induced dissociation of tight couple ribosomes. AB - Ribosomes from Escherichia coli have been shown to undergo subunit dissociation at elevated hydrostatic pressure. This holds for both crude and highly purified ribosomes. No inhibitory effect could be detected by addition of either the S100 supernatant, or tRNA, polyuridylic acid, and spermine. Light scattering experiments at pressures up to 1000 bar reveal different susceptibility of tight couple and loose couple ribosomes toward pressure dissociation. Tight couples are subjected to EF-Tu-catalyzed binding of aminoacyl-tRNA, thus yielding a model system of the elongating ribosome before the peptidyl transfer step. High pressure dissociation of this compound suggests that enzymatic binding converts tight couples into loose couples. A hypothesis referring to conformational changes during the elongation cycle is presented. PMID- 2199218 TI - Regulation of the level of uncoupling protein in brown adipose tissue by insulin requires the mediation of the sympathetic nervous system. AB - The role of the sympathetic nervous system in the regulation by insulin of the level of uncoupling protein in brown adipose tissue has been examined. The amount of uncoupling protein was substantially reduced in streptozotocin-diabetic rats, while insulin replacement to diabetic animals induced a partial restoration. Unilateral denervation of the interscapular brown fat pads also lowered the amount of uncoupling protein, and in diabetic animals inhibited the stimulation of the level of the protein by insulin replacement. Maintenance of normal uncoupling protein levels requires both insulin and the sympathetic system; regulation of the protein by insulin involves sympathetic mediation. PMID- 2199219 TI - Special issue to celebrate the 100th birthday of Karl-Heinrich Bauer. PMID- 2199217 TI - Properties and nature of a cysteine proteinase inhibitor located in keratohyalin granules of rat epidermis. AB - The pI 4.7, 14.5 kDa hematoxylin-stainable protein (HSP) from rat epidermis inhibited the activities of the cysteine proteinases papain, ficin, cathepsins B, H and L with similar inhibitory characteristics as recombinant cystatin-alpha. Proteinases of other classes were not inhibited. The inhibitory activity of HSP was heat stable in the wide pH range of 3.0-10.0. Polyclonal antibodies against HSP cross-reacted with cystatin-alpha and the molecular mass of HSP was similar to that of cystatin-alpha, though its isoelectric point was different. The in vivo location of both HSP and cystatin-alpha is on keratohyalin granules in epidermis as detected by indirect immunofluorescence technique using individual antibodies. Therefore it is highly probable that HSP is a cystatin-alpha derivative or a very similar proteinase inhibitor belonging to a family of cystatins. PMID- 2199220 TI - 100th anniversary of the birthday of Karl-Heinrich Bauer. PMID- 2199221 TI - Proposal for a new carcinoid tumour staging system based on tumour tissue infiltration and primary metastasis; a prospective multicentre carcinoid tumour evaluation study. West German Surgical Oncologists' Group. AB - In order to evaluate the significance of different prognostic factors, a multicentre prospective carcinoid tumour study was launched in early 1987, under the auspices of CAO (Chirurgische Arbeitsgemeinschaft Onkologie, a West German surgical oncologists' collaboration group) and UICC (Union Internationale Contre le Cancer). Up to March 1990 we received and evaluated clinical data from 94 patients from 16 hospitals. Carcinoid localization was distributed as follows: stomach 4, duodenum 7, pancreas 3, jejunum 5, ileum 21, Meckel's diverticulum 1, appendix 29, colon 5, rectum 14, and 5 cases of tumour metastases of unknown origin. The mean age was 54.7 years, overall sex ratio (m/w) was 1:1.09. Thirty one patients presented with simultaneous lymph-node metastases and 27 with distant metastases. Based on these data, a metastases staging system (four stages) has been defined for study stratification. This work also aims at evaluating the correlation of tumour diameter and tumour tissue invasion with primary metastases occurrence; primary tumour diameter remains the most important prognosis-related factor for appendiceal location. For other locations, tumour tissue invasion can be markedly better correlated with regional lymphatic and distant spread than is the case with tumour diameter. Tumour tissue invasion has, therefore, been selected to define a local staging (four stages) for further study stratification. Tumour location, metastases stage and local stage combined, best describe the current state of the disease and will serve to evaluate further pathological stratification and to correlate survival data. PMID- 2199222 TI - Influence of endorectal ultrasound on surgical treatment of rectal cancer. AB - Refined surgical treatment of carcinoma of the rectum, such as sphincter preserving operations, pouch anal anastomosis, and pre-operative irradation require exact assessment of tumor and lymph-node involvement before therapy. To improve pre-operative staging we used endorectal ultrasound to determine the depth of tumor infiltration and the presence of lymph-node metastases. A 7.0 MHz transducer (Bruel and Kjaer, Denmark) was used in the pre-operative staging of 110 patients with rectal carcinomas. In 90% of the cases it was possible to perform a correct tumor staging pre-operatively in comparison with histopathology. Sensitivity for detection of perirectal fat infiltration was 96% and the negative predictive value was 96%. Lymph-node involvement was accurately identified in approximately 80% of the cases. Endorectal ultrasound is a highly accurate tool in the pre-operative staging of rectal carcinoma, as well as in the detection of lymph-node involvement. It will identify patients suitable for sphincter-saving procedures or local treatment and define those with a considerable risk of local recurrence, where combined surgery and radiotherapy may be considered. PMID- 2199223 TI - Current status of immunoscintigraphy in colorectal cancer--results of 5 years' clinical experiences. AB - In 100 patients with suspected colorectal cancer, findings of conventional diagnostic methods were compared with immunoscintigraphy results. In a first trial 131-J-labelled F (ab') 2-fragments against CEA and CA 19-9 were used in 42 patients. Evidence was confirmed by surgical exploration in 69% of cases and by close follow-up examination in 31%. In a second trial 58 patients were included, and 81% of these were explored surgically. Conventional diagnostic methods achieved better results in both series in imaging liver and extrahepatic tumor manifestations, and in both series immunoscintigraphy was especially disappointing with regard to extrahepatic tumor diagnosis (sensitivity 23% and 38%, respectively). Accuracy could not be improved by technical modifications such as change of antibodies, radiolabels or imaging techniques. The value of immunoscintigraphy as a helpful tool for the operative management of metastatic or recurrent colorectal cancer must, therefore, be viewed critically. PMID- 2199224 TI - Interventional radiological treatment of malignant biliary obstruction. AB - Percutaneous transhepatic procedures have gained a strong position in the diagnosis and treatment of malignant biliary obstruction. Diagnostic cholangiography can easily be converted into therapeutic drainage, which is often the first step towards further diagnostic work-up (biopsy, percutaneous cholangioscopy) and tumour ablation and/or intraductal irradiation. Plastic endoprostheses and balloon- or self-expandable metallic stents are the therapeutic alternatives to achieve permanent internal drainage of bile. PMID- 2199225 TI - [V. I. Lenin and the protection of the health of women and children]. PMID- 2199226 TI - [Insurance medicine--supplementary means for health protection]. PMID- 2199227 TI - [The differential diagnosis, treatment and prevention of malaria]. PMID- 2199228 TI - Hormonal and biochemical changes during treatment of endometriosis with the luteinizing hormone-releasing hormone (LH-RH) agonist [D-Trp6,des-Gly-NH2(10)]LH RH ethylamide. AB - The effect of medical oophorectomy induced by treatment with the luteinizing hormone-releasing hormone (LH-RH) agonist [D-Trp6,des-Gly-NH2(10)]LH-RH ethylamide was studied in 34 patients with laparoscopically proven endometriosis. Tamoxifen was administered during the 1st month of therapy to prevent flare-up of the disease during the estrogen surge. Fifteen women had a decrease of their laparoscopy scores translated into an improvement in the stage of disease, whereas in 12 others, the decrease in their scores was not enough to allow a change of disease stage. The 2nd laparoscopy was not performed in 7 women. Medical oophorectomy, after daily injection of the LH-RH agonist (LH-RH-a), was accompanied by low levels of circulating estradiol. The serum concentration of all delta 4-3-ketosteroids was significantly decreased during medical oophorectomy, whereas the level of circulating delta 5-3 beta-hydroxysteroids was not altered except for pregnenolone. The present data indicate that medical oophorectomy induced by an LH-RH-a in association with tamoxifen is a very efficient and well tolerated therapy in endometriosis. PMID- 2199229 TI - Predicting pregnancy outcome by the observation of a gestational sac or of early fetal cardiac motion with transvaginal ultrasonography. AB - Transvaginal ultrasound (US) allows for observation of the gestational sac and cardiac motion as early as 3 and 4 weeks after ovulation, respectively. The purpose of this study was to determine how well the first observation of cardiac motion, using weekly transvaginal US examinations, predicted pregnancy outcome. Three hundred sixteen pregnancies wherein the date of ovulation was known and a single gestational sac was visualized at 3 weeks after ovulation were studied. Cardiac motion was first detected at 4 weeks after ovulation in 226 (71.5%), and at 5 weeks in 67 (21.2%). In 23 patients, cardiac motion was never observed. In those patients with cardiac motion visible at 4 weeks after ovulation, 94.2% have subsequently delivered viable infants. This contrasts with only 70.1% for those patients who first had observable cardiac motion 1 week later (P = 6.7 X 10(-6]. This study demonstrates that the solo finding of a gestational sac is a poor predictor of pregnancy outcome (82.3% accurate) and that the earlier that cardiac motion is initially observed, the better the pregnancy prognosis. PMID- 2199230 TI - Transcervical intrafallopian transfer of zygotes. AB - Reportedly, gamete intrafallopian transfer and zygote intrafallopian transfer are successful methods in assisted conception. This pilot study describes the experiences and results of a recently developed technique of vaginal transcervical intrafallopian transfer. In a group of 38 women with unexplained infertility, oocytes were retrieved. In 25 patients, pronucleate embryos were transferred to the fallopian tubes. A positive pregnancy test was reported in 8 cases. Considerations pertaining to this method and technical implications are discussed. PMID- 2199231 TI - Cervical mucus and serum estradiol as predictors of response to progestin challenge. AB - The present study was undertaken to assess the correlation between and relative predictive value of each of the following variables and progestin-induced withdrawal bleeding: cervical mucus appearance, serum E2 level, patient age, duration of amenorrhea, smoking and exercise habits, and body composition. Of 120 oligomenorrheic and amenorrheic women evaluated, only cervical mucus appearance and serum E2 level were significantly associated with response to progestin challenge. A multivariate logistical regression analysis showed cervical mucus to be the most predictive variable followed by serum E2 level. No absolute E2 level was found to discriminate between those who did and those who did not have withdrawal bleeding after progestin challenge. These data suggest that office examination of cervical mucus may be a useful indicator and guideline in planning therapy. PMID- 2199232 TI - Clinical usefulness of CA-125 levels in the menstrual discharge in patients with endometriosis. PMID- 2199233 TI - The choroidal circulation and retinal metabolism--an overview. PMID- 2199234 TI - The blood-brain interface. AB - The properties of the blood-brain barrier are those of the capillary endothelium in brain. This endothelium contrasts with that elsewhere in being sealed with tight junctions, having a high electrical resistance and low permeability to polar solutes. It is exceptional in having a paucity of pits and vesicles, a specialised enzyme content and a high density of mitochondria. Functionally, a range of transport mechanisms allow rapid movement of certain specific metabolic substrates. Ion pumps are concerned with secretion of brain interstitial fluid and regulation of its ionic concentration. The retinal capillaries are largely identical to those of the brain, but entry of solutes into retina is also determined by the properties of the pigment epithelium, functionally separating the retina from the highly vascular choroid. A clear difference lies in the greater resistance of cerebral microvessels to diabetic damage. The mechanism of this difference is unclear, but may relate to a better control of the brain interstitial fluid at a lower glucose concentration than is possible in the retinal interstitial fluid. PMID- 2199235 TI - Development of the choroid and related structures. AB - The development of the choriocapillaris and the choroid is described using light and electron microscopy. Up to the seventh week after conception, the endothelium of the choriocapillaris is thick and contains many cytoplasmic vesicles. By the ninth week the endothelium flattens and becomes vesiculated. Fenestrations are found as early as the seventh week, whereas the continuous basement membrane is only observed at the ninth week. The first choroidal arterioles and venules can be seen during the fifteenth week and the arteries and veins become distinguishable at the twenty-second week. Haller's and Sattler's layers are both venous and arterial at the time of their first appearance. PMID- 2199236 TI - In vivo choroidal circulation and its watershed zones. AB - In vivo studies on choroidal vascular bed have shown that the posterior ciliary arteries (PCAs) right down to their terminal arterioles in the choroid have strictly segmental blood flow and they behave as end-arteries. These studies totally contradict the picture shown by all the postmortem cast studies of the choroidal vascular bed as a freely communicating system. The in vivo pattern helps to explain the typically localised nature of inflammatory, ischaemic, degenerative and metastatic nature of the choroidal lesions. Like other end arterial vascular systems in the body, the choroidal vascular bed has watershed zones situated between the various PCAs, the short PCAs, the choroidal arteries, the arterioles, and the vortex veins. The end-arterial nature of the choroidal vasculature and the existence of watershed zones in the choroid are of great clinical importance; their role in the production of various ischaemic lesions in the choroid, anterior ischaemic optic neuropathy (AION) and other ischaemic disorders of the optic nerve head is discussed. PMID- 2199237 TI - Permeability of ocular vessels and transport across the blood-retinal-barrier. AB - This paper reviews quantitative studies on the permeability of retinal and choroidal vessels and the exchange of nutrients over the blood retinal barrier (BRB). The fenestrated capillaries in the choroid are very permeable to low molecular weight substances; sodium permeability in the choroid is probably 50 times that in skeletal muscle. This results in high concentrations and rapid turnover of nutrients in the extra-vascular compartment of the choroid. Free diffusion is restricted by the pigment epithelium barrier. Also the retinal capillaries, with tight junctions between the endothelial cells, have very low permeability even to sodium. The uptake index technique has provided evidence for several carrier systems in the BRB; hexoses, neutral and basic amino acids, and monocarboxylic acids, very similar to those found in the brain. At least for glucose and lactate these carriers operate at both levels of the BRB; the RPE and the endothelium of the retinal capillaries, and in both directions; i.e. inwards and outwards. PMID- 2199238 TI - Pulsatile flow in the choroidal circulation: a preliminary investigation. AB - A preliminary investigation has been made of choroidal blood flow using a computer-aided image analysis approach to interpretation of indocyanine green (ICG) dye choroidal angiograms. The goal of the study was to characterise blood flow through the choroidal arteries vs. choroidal capillaries and veins. The methods of analysis used are briefly reviewed, and preliminary data obtained mainly from monkey eyes are presented. Preliminary conclusions are made regarding the relationship between compliance of choroidal arterial vessels and blood flow through them. PMID- 2199239 TI - Control of retinal and choroidal blood flow. AB - Earlier studies on the control of retinal and choroidal blood flow are reviewed and some recent observations on the effects of light on retinal metabolism and retinal and choroidal blood flow in monkeys (Macaca fascicularis) are reported in preliminary form. The retina is nourished by the retinal blood vessels, where blood flow is autoregulated and the choroidal blood vessels where autoregulation is absent. Studies with the deoxyglucose method of Sokoloff indicate that flickering light tends to increase the metabolism of the inner retina, while constant light reduces the metabolism in the outer retina. Retinal blood flow in flickering light, 8 Hz, is higher than in constant light. The sympathetic nerves of the choroid are probably involved in a protective mechanism, preventing overperfusion in fight and flight situations with acute increments in blood pressure. The facial nerve contains parasympathetic vasodilator fibres to the choroid; the physiological significance of these fibres is unknown. The neuropeptides NPY, VIP and PHI are likely to be involved in autonomic reflexes in the eye. PMID- 2199240 TI - Processing and transport of retinoids by the retinal pigment epithelium. AB - Recent developments regarding our understanding of retinoid processing and transport during the visual cycle and related events are reviewed. Retinoids are bound and protected by a cohort of retinoid binding proteins, each of which is unique. The production of retinol (Vitamin A) derivatives is accomplished by a group of membrane-bound enzymes, some of which appear to be coupled in their actions. PMID- 2199241 TI - Regional variation within the interphotoreceptor matrix from fovea to the retinal periphery. AB - The interphotoreceptor matrix in the human retina comprises a highly organised extracellular compartment. Using fluorescent labelled peanut agglutinin and the cationic dyes Cupromeronic and Cuprolinic Blue, unique cylindrical domains surrounding cone photoreceptors can be demonstrated. These cone specific domains are relatively insoluble and are closely adherent to cone photoreceptors and to the pigment epithelium, suggesting that these structures may play a role in retinal attachment. PMID- 2199242 TI - Control of subretinal fluid: experimental and clinical studies. AB - Experimental work shows that subretinal fluid is removed both by active transport across the retinal pigment epithelium (RPE) and by passive hydrostatic and oncotic forces that work most effectively when the RPE barrier has been damaged. The retina will stay attached whether or not the RPE is intact--but retinal function requires the RPE barrier and thus active transport is the primary mechanism of subretinal fluid control. RPE fluid transport is normally limited by the retina (which resists water flow from the vitreous) but can be quite powerful when a reservoir of subretinal fluid is present. Clinical serous detachments are unlikely to form solely as a result of small RPE defects or leaks, since the active and passive transport systems for removing subretinal fluid are both so strong. It is suggested that the primary pathology in most serous retinopathy is a diffuse metabolic or vascular abnormality of RPE fluid transport, and that RPE defects or leaks are necessary but only secondary components of the disease. Several hypotheses for removing subretinal fluid therapeutically are considered in terms of their physiology. The subretinal space between the photoreceptors and the retinal pigment epithelium (RPE) is the remnant of the embryonic optic vesicle. In the developed eye the subretinal space is of minimal size, but no tissue junctions form across it and it can re-open under pathological conditions of retinal detachment. In a sense, the title of this paper is misleading since normally there should be no subretinal fluid to control. However, ocular mechanisms are necessary to prevent an accumulation of fluid, and to remove it under conditions of stress or disease. PMID- 2199243 TI - Disruption of the choroidoretinal interface by toxoplasma. AB - Toxoplasmosis is a common zoonotic infection of the retina caused by Toxoplasma gondii. The disease causes severe damage that affects the retina and subjacent choroid. Invasion of the retinal cells by the parasite leads to the major damage seen in the retina. Subsequent reactions to the invasion by toxoplasma leads to the influx of inflammatory cells. Although hypersensitivity reactions have been described to both toxoplasma and to retinal autoantigens, the major disruption of the choroidoretinal interface is probably secondary to the tissue invasion by the parasite. Patients with AIDS may show extensive necrosis of the retina in the absence of inflammatory cells. Healing of the active lesion leads to scar formation. Toxoplasma retinochoroiditis may be pigmented, nonpigmented or punched out. Vascular anastomoses between the retina and choroid, retinal and subretinal neovascularization may occur in the aftermath of choroidoretinal interface disruption. PMID- 2199244 TI - Tumour-associated retinal pigment epitheliopathy. AB - Choroidal tumours are associated with several degenerative changes in the overlying tissues, which can be called 'Tumour-Associated Retinal Pigment Epitheliopathy (TARPE)'. These changes include (i) proliferation, detachment, atrophy, and metaplasia of the retinal pigment epithelium, (ii) the accumulation of hard and soft drusen and basal laminar deposits in Bruch's membrane, (iii) disorganisation of the choriocapillaris, (iv) atrophy, cystic degeneration and detachment of the retina. The changes at the chorio-retinal interface are clinically relevant because they can exacerbate visual loss. In addition, they can be misinterpreted on ophthalmoscopy and fluorescein angiography. An amelanotic choroidal tumour may appear to be pigmented on ophthalmoscopy because of lipofuscin and melanin accumulation overlying the tumour. The hyperfluorescence associated with pigmented choroidal melanomas is more likely to be related to degenerative changes in the retinal pigment epithelium than to dye leakage from abnormal tumour vessels. PMID- 2199245 TI - The correspondence between U.K. 'action levels' for lead in blood and in water. AB - This paper considers whether the Department of the Environment's water lead concentration criterion for lead pipe replacement and action in individual cases, i.e. 50 micrograms/l in any sample, is too high when set against the Department of Health's advisory action limit for blood lead concentration of 25 micrograms/100 ml. The relationships between blood lead and water lead concentrations found in the Glasgow and Ayr duplicate diet studies, together with unpublished data from Glasgow and Liverpool, indicate that over 10% of people exposed to an average water lead concentration of 100 micrograms/l (the earlier action level) would have blood lead concentrations above 25 micrograms/100 ml, as would about 4% of those exposed to 50 micrograms/l (the Maximum Admissible Concentration in an EEC Directive). For adults, average water lead concentrations should not exceed 30 micrograms/l to ensure compliance with the limit for blood lead, i.e. so that not more than 2% exceed 25 micrograms/100 ml. However, for one of the critical groups, bottle-fed infants (whose diet is 90% water), average water lead concentrations should not exceed 10-15 micrograms/l. The WHO's Provisional Tolerable Weekly Intake (PTWI) for children (25 micrograms/kg body weight) also implies that their water lead concentrations should not exceed 10-15 micrograms/l. PMID- 2199246 TI - CA 125 and OA 3 as target antigens for immunodiagnosis and immunotherapy in ovarian cancer. PMID- 2199247 TI - Cervical cancer as a natural phenomenon. AB - Recognizing cervical cancer as a natural stochastic phenomenon, that is in the first stage of its self-organization into a new biological dissipative structure (initiation) and sustaining its development in the second stage (promotion), is a basic requirement in conquering cancer and preventing neoplastic disease, i.e., the third stage of neogenesis (progression). A dissipathogenic state inside an organism is the only common primary cause of neoplasia. Thus, medical thermodynamics clarifies why so many non-specific factors enable the origin of cervical cancer, that is, can cause cervical dissipathogenic states. This thermodynamical theory abolishes opposition and unites the heretofore cellular neoplastic theories by bringing them to an atomic level. Diagnosis and treatment of dissipathogenic processes implies true causal prophylaxis of cancer, therapy of which always has to encompass its environment. PMID- 2199248 TI - Transabdominal and transvaginal color Doppler in the assessment of fetomaternal circulation during all three trimesters of pregnancy. PMID- 2199249 TI - Regulation of carbohydrate metabolism by glucose 1,6-bisphosphate in extrahepatic tissues; comparison with fructose 2,6-bisphosphate. PMID- 2199250 TI - Biosynthesis of collagen crosslinks. PMID- 2199251 TI - Heme production in animal tissues: the regulation of biogenesis of delta aminolevulinate synthase. PMID- 2199253 TI - Biochemical aspects of drug-induced Parkinson's disease. PMID- 2199252 TI - Molecular action of progesterone. PMID- 2199254 TI - Membrane lipid phase behaviour and lipid-protein interactions. PMID- 2199255 TI - Aspartate aminotransferases and malate dehydrogenases: patterns of evolution. PMID- 2199256 TI - Alcohol dehydrogenases. PMID- 2199257 TI - Glutathione S-transferases. PMID- 2199258 TI - Hexokinases and glucokinases. PMID- 2199259 TI - The fructose-1,6-bisphosphate aldolases: same reaction, different enzymes. PMID- 2199260 TI - Proteoglycans: structure and function. PMID- 2199261 TI - Structural variability of large and small chondroitin sulphate/dermatan sulphate proteoglycans. PMID- 2199263 TI - Large-scale manufacture of monoclonal antibodies for use in humans. PMID- 2199262 TI - Purification of recombinant proteins for pharmaceutical use. PMID- 2199264 TI - Metabolic mosaics: a computer-assisted learning package for metabolism. PMID- 2199265 TI - Mutant insulins: a case-study for computer-assisted learning. PMID- 2199266 TI - Amino acid sequences of aspartate aminotransferases: the cytosolic isoenzymes from yeast and from human liver. PMID- 2199267 TI - Site-directed mutagenesis as a tool for the study of the allosteric control of pyruvate kinase. PMID- 2199268 TI - Peptidases of Helix aspersa. PMID- 2199269 TI - Immobilization of proteolytic enzymes. PMID- 2199270 TI - Design and synthesis of putative inhibitors of glucosamine synthetase. PMID- 2199271 TI - Regeneration of yeast protoplasts prepared using Novozym 234. PMID- 2199272 TI - Isolation of fragments with a blocked N-terminus by selective labelling with 9 fluorenylmethyl chloroformate. PMID- 2199273 TI - Immunizing against adipose plasma membranes to reduce body fat: effects on plasma metabolites and insulin. PMID- 2199275 TI - Effects of the pyridinamines octenidine and pirtenidine on yeast mitochondrial function. PMID- 2199276 TI - Two distinct modes of action, namely ab initio and ad finem, of the yeast culture Yea-Sacc on ruminal fermentation in sheep. PMID- 2199274 TI - Identification of a putative Plasmodium berghei (a rodent malaria parasite) reticulocyte receptor. PMID- 2199277 TI - The suggestion that the yeast cell Saccharomyces cerevisiae may absorb sufficient hydrogen ions to increase ruminal fluid pH is untenable. PMID- 2199278 TI - Class-switch recombination in extrachromosomal DNA substrates in murine pre-B cells. PMID- 2199279 TI - Kidney IGF-I mRNA in initial renal hypertrophy in experimental diabetes in rats. AB - It has recently been demonstrated that immunoassayable kidney insulin-like growth factor I concentration increases 24-48 h after induction of diabetes, preceding the initial renal hypertrophy. To elucidate whether this increase is due to increased local production we studied rat kidney insulin-like growth factor I gene expression during the first four days after induction of streptozotocin diabetes. Eighteen hours after injection with streptozotocin the diabetic animals were divided into two groups, one of which was treated with insulin, and daily for four days animals from each group were taken out for investigation. After four days the wet kidney weight had increased from baseline by 20% (from 687 +/- 23 to 827 +/- 6 mg (mean +/- SEM), p less than 0.01) in the untreated diabetic group, while no significant increase occurred in the insulin-treated group (687 +/- 23 vs 732 +/- 21 mg, NS). Kidney insulin-like growth factor I increased rapidly from baseline, the rise amounting to 52% after 48 h (from 271 +/- 11 to 411 +/- 32 ng/g, p less than 0.01) with a decline to control level on day four in the untreated diabetic group. Kidney insulin-like growth factor I remained unchanged in the insulin-treated diabetic group. Insulin-like growth factor I mRNA was measured by solution-hybridization assay. No differences were found in kidney insulin-like growth factor I mRNA between the two diabetic groups over the study period, while in liver, insulin-like growth factor I mRNA tended to be lower on day four in diabetic rats when compared to insulin-treated rats (p = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2199281 TI - Action profiles of fast onset insulin analogues. AB - Recombinant DNA technology allows the production of insulin analogues with faster absorption rates from subcutaneous tissue as compared to conventional human regular insulin. We report the time-action profiles of 12 U subcutaneously injected insulin analogues (B9Asp + B27Glu or B10Asp) as evaluated against human regular insulin by means of the euglycaemic clamp technique (blood glucose 5.0 mmol/l) in healthy men. After injection of 12 U of either insulin preparation identical values were found for maximal insulin action (maximal glucose infusion rate, time to peak action), total amount of glucose infused as well as area under the curve of glucose infusion rate. Half-maximal glucose infusion rate was reached significantly earlier after injection of modified insulins (mean +/- SD 38 +/- 7 and 43 +/- 5 min) as compared to regular insulin (56 +/- 14 min, p less than 0.01). Forty-five min after injection of both insulin analogues glucose infusion rate had increased by 7.4 +/- 1.8 or 6.1 +/- 1.8 mg.kg-1.min-1, reflecting 83 +/- 27 or 67 +/- 15% of maximal regular insulin action. In conclusion, the two tested insulin analogues showed similar action profiles, but a significantly faster onset of action as compared to regular insulin. PMID- 2199282 TI - Going both ways: bispecific antibodies and targeted cellular cytotoxicity. PMID- 2199280 TI - Direct relationship of antepartum glucose control and fetal erythropoietin in human type 1 (insulin-dependent) diabetic pregnancy. AB - In the present study the antepartum relationship between maternal diabetic glucose control and fetal hypoxaemia was examined in 44 Type 1 (insulin dependent) diabetic and 23 non-diabetic control pregnancies. Maternal HbA1C was used to assess maternal integrated blood glucose control while fetal metabolic control was evaluated by antepartum glucose, insulin, and C-peptide determinations in amniotic fluid at elective caesarean delivery. Fetal hypoxaemia was assessed indirectly by fetal umbilical vein plasma erythropoietin level at delivery. A prospectively developed statistical pathway model was used to examine the relationship of these variables. In applying forced stepwise multiple regression with this model, we observed in the diabetic subjects that mean maternal HbA1C during the last month of pregnancy correlated significantly with fetal umbilical venous erythropoietin at delivery (r = 0.57, p less than 0.001). Additional significant contributions to umbilical venous erythropoietin were found for amniotic fluid glucose and amniotic fluid insulin when these two independent variables were added in stepwise fashion (p less than 0.01). We conclude that in diabetic pregnancy, antepartum control of maternal hyperglycaemia is a significant factor associated with fetal hypoxaemia. We speculate that this effect is mediated through perturbations which accelerate fetal metabolism and which is expressed by amniotic fluid levels of glucose and insulin. PMID- 2199283 TI - Animal models of spontaneous diabetic kidney disease. AB - Kidney disease, characterized by proteinuria and glomerular lesions, is a common complication of spontaneous diabetes mellitus in many animal species. It occurs in animals with hypoinsulinemia, hyperinsulinemia, or impaired glucose tolerance. The renal functional and structural abnormalities in spontaneously diabetic animals resemble human diabetic nephropathy in many respects. Mesangial expansion and glomerular basement membrane thickening, two structural hallmarks of diabetic glomerulopathy in humans, are the most frequently encountered lesions in animals. In addition, a nodular form of mesangial expansion that resembles but is not identical with human nodular glomerulosclerosis or the Kimmelstiel-Wilson lesion has been observed in some animal models. Other abnormalities, such as exudative hyaline lesions and arteriolar hyalinosis, have also been noted occasionally in other models. Although diabetic animals may develop kidney disease that resembles human diabetic nephropathy, no single animal model develops renal changes identical to those seen in humans. Nonetheless, animal models with spontaneous diabetic kidney disease may be useful for investigating the mechanisms of development of diabetic nephropathy and the effects of various treatment modalities on the progression of renal disease. PMID- 2199284 TI - Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF). AB - Interleukin 1 (IL 1), IL 6, and tumor necrosis factor (TNF) are typical examples of multifunctional cytokines involved in the regulation of the immune response, hematopoiesis, and inflammation. Their functions are widely overlapping but each shows its own characteristic properties. IL 6 was originally identified as a B cell differentiation factor, and thus one of the major functions of IL 6 is antibody induction. Transgenic mice have provided much needed information on the pathophysiological role of cytokines. With IL 6 transgenic mice, deregulation of the IL 6 expression was suggested to be involved in the generation of plasmacytoma/myeloma and mesangium proliferative glomerulonephritis. The cis regulatory elements and trans-acting nuclear factor (or factors) for the IL 6 expression (NF-IL 6) have been identified. NF-IL 6 was shown to be a member of a C/EBP family, and the possible involvement of NF-IL 6 not only in the IL 6 regulation but also in the induction of various acute phase proteins was also observed. The findings suggest the presence of a positive regulatory loop in acute-phase reaction. IL 1 receptor belongs to an Ig superfamily, but the IL 6 receptor is a member of a newly identified cytokine receptor family. The IL 6 receptor system was shown to be composed of a ligand binding chain and a signal transducing molecule. IL 6 was found to trigger the association of these two polypeptide chains. This unique mechanism may be applied to other cytokine receptor systems. PMID- 2199285 TI - Integrins and other cell adhesion molecules. AB - Cell-cell and cell-substratum interactions are mediated through several different families of receptors. In addition to targeting cell adhesion to specific extracellular matrix proteins and ligands on adjacent cells, these receptors influence many diverse processes including cellular growth, differentiation, junction formation, and polarity. Several families of adhesion receptors have been identified. These include: 1) the integrins, heterodimeric molecules that function both as cell-substratum and cell-cell adhesion receptors; 2) the adhesion molecules of the immunoglobulin superfamily, which are involved in cell cell adhesion and especially important during embryo-genesis, wound healing, and the inflammatory response; 3) the cadherins, developmentally regulated, calcium dependent homophilic cell-cell adhesion proteins; 4) the LEC-CAMs, cell adhesion molecules with lectin-like domains that mediate white blood cell/endothelial cell adhesion; and 5) homing receptors that target lymphocytes to specific lymphoid tissue. In this review we summarize recent data describing the structure and function of some of these cell adhesion molecules (with special emphasis on the integrin family) and discuss the possible role of these molecules in development, inflammation, wound healing, coagulation, and tumor metastasis. PMID- 2199286 TI - Brown adipose tissue thermogenesis: interdisciplinary studies. AB - Energy expenditure for thermogenesis in brown adipose tissue (BAT) serves either to maintain body temperature in the cold or to waste food energy. It has roles in thermal balance and energy balance, and when defective, is usually associated with obesity. BAT can grow or atrophy; it is usually atrophied in obese animals. Control of BAT thermogenesis and growth is by the sympathetic nervous system, with integration of signals in the hypothalamus. Sensory nerves may also be involved. Understanding the control of growth and differentiation of BAT is important for discovering how to reactivate it is obesity. Studies on control of gene expression in BAT are concentrating on thermogenically important components such as the uncoupling protein (which allows BAT mitochondria to operate in a thermogenic uncoupled mode), lipoprotein lipase (which allows BAT to compete with white adipose tissue for dietary lipid), and thyroxine 5'-deiodinase (which allows endogenous triiodothyronine generation, part of the control of differentiation and growth of BAT). Differentiation of BAT cell precursors in culture has recently been achieved. BAT is present in adult humans and some anti obesity drugs are targeted to stimulation of BAT thermogenesis. However, extrapolation to humans of results of studies of BAT requires the development of novel approaches to the noninvasive assessment of amount and function of human BAT. PMID- 2199287 TI - Secondary 18O isotope effects as a tool for studying reactions of phosphate mono , di-, and triesters. AB - Secondary 18O isotope effects have been developed as a tool for determining transition state structures in enzymatic and nonenzymatic phosphoryl transfer reactions. 18O substitution in the nonbridge oxygens of a phosphoryl group makes the reaction go faster when the bond order is higher to these oxygens in the transition state than in the reactant, whereas the reaction goes slower if the bond order is less. The isotope effects are measured by the remote label method, using an isotope ratio mass spectrometer for analysis. The bond order to p nitrophenolate ion when it is the leaving group is indicated by the secondary 15N isotope effect in the nitro group, with a value of 1.0028 representing nearly complete bond cleavage. It appears that the transition states for phosphoryl transfer have no more than one negative charge on the nonbridge oxygens, so that reactions of monoesters are dissociative, reactions of triesters are associative, and reactions of diesters are SN2 with half bond order to entering and leaving groups. PMID- 2199288 TI - Effect of long-term treatment with omeprazole on serum gastrin and serum group A and C pepsinogens in patients with reflux esophagitis. AB - Twenty-nine nongastrectomized and three partially gastrectomized patients with chronic reflux esophagitis resistant to 12 weeks' treatment with histamine H2 receptor antagonists were treated with a daily oral dose of 20-40 mg of omeprazole for 12-30 months. Basal serum gastrin, serum pepsinogen A, and serum pepsinogen C concentrations were monitored at regular intervals. Serum gastrin levels significantly (P less than 0.01) increased threefold to fourfold during the first 1-2 months of the study when all patients ingested 40 mg of omeprazole daily. Dose reduction to 20 mg did not significantly decrease gastrin levels. Serum gastrin levels showed a trend to further increase after the first 3 months of treatment, reaching statistically significant differences for values from the 3-12-month period (P less than 0.05) and from the 3-24-month period (P less than 0.005). Women and patients with high basal serum gastrin levels before omeprazole treatment were more likely to achieve higher serum gastrin levels during omeprazole treatment. Serum pepsinogen A and C levels were significantly (P less than 0.01) increased at all time intervals during long-term treatment with omeprazole. No significant tendency toward higher serum pepsinogen C levels in time was observed. However, serum pepsinogen A levels and the ratio of pepsinogen A to pepsinogen C further increased significantly (P less than or equal to 0.05) during the initial 3-12-month period. However, this trend was not observed anymore afterward. Antrectomized patients did not show increases in serum gastrin and serum pepsinogen A and C levels, suggesting that hypergastrinemia may be involved in the observed hyperpepsinogenemia. PMID- 2199289 TI - Efficacy of different doses of cimetidine in the treatment of reflux esophagitis. A review of three large, double-blind, controlled trials. AB - Four different cimetidine dosage regimens--800 mg u.i.d. HS or nocte, 800 mg u.i.d. dinnertime, 400 mg q.i.d., and 800 mg b.i.d.--were investigated for the treatment of reflux esophagitis in three independent large-scale, double-blind, controlled multicenter trials in which more than 1100 patients participated. Analysis of the data shows that the percentage of endoscopic healing after 6 and 12 weeks of treatment was fairly constant in patients with the same endoscopic grade of severity of reflux esophagitis at the start of treatment, whether they were treated with 800 mg u.i.d. (HS or dinnertime), 800 mg b.i.d., or 400 mg q.i.d. Healing percentages after 12 weeks of therapy ranged from 79%-92% for grade I, from 65%-70% for grade II, and from 41%-54% for grade III. Differences within the three grades for the various treatment regimens did not reach statistical significance. Symptomatic improvement was evaluated with the Standardized Total Heartburn Index, which is based on frequency and severity of heartburn as well as on the number of patients in the study population experiencing heartburn at a given time in relation to the total heartburn load at the start of the study. All three treatment schedules resulted in a substantial reduction of the Standardized Total Heartburn Index. Treatment with cimetidine, 800 mg u.i.d., for 6-12 weeks was efficacious in the majority of patients with reflux esophagitis grade I-III. Symptom relief was superior with dosing after dinner time compared with dosing HS. A single dose of 800 mg administered after the evening meal approached the efficacy achieved with 400 mg q.i.d. Based on these objectives and symptomatic results, a u.i.d. cimetidine regimen appears to be the treatment of choice for the initial approach of a patient with reflux esophagitis. A u.i.d. regimen may enhance patient compliance, comfort, and safety as well as ease of prescription while also being less expensive. PMID- 2199290 TI - Failure of colchicine to improve short-term survival in patients with alcoholic hepatitis. AB - Colchicine treatment was used in this randomized placebo-controlled trial in patients with severe acute alcoholic hepatitis [serum bilirubin greater than or equal to 5 mg/dL (85.5 mumol/L) mean, 17.5 +/- 7.5 mg/dL (299.25 +/- 128.25 mumol/L)]. Hospitalization mortality and morbidity and the effect on biochemical test results were the end points of the treatment. Patients in the two groups were evenly matched by demographics and laboratory test results. Mean time to study entry was less than 7 days from admission. The duration of the trial was 30 days. Thirty-six patients (24 men, 12 women) received colchicine (1 mg orally every morning) and 36 (25 men, 11 women) received an identical placebo. Seven (19%) colchicine-treated and six (17%) control patients died during the index hospitalization after a mean of 17.4 +/- 10.8 and 17.8 +/- 5.3 days, respectively (NS). During a 4-month follow-up period from entry into the trial, there were two additional deaths in each group. No differences between placebo- and colchicine treated patients were observed in any of the laboratory parameters (serum bilirubin, aspartate transaminase, alanine transaminase, prothrombin activity, albumin, white blood cell count, hemoglobin, and creatinine) that were followed up over the 30-day treatment period. The frequency of complications did not differ statistically between the two groups. This study showed no effect of colchicine treatment on mortality and morbidity of severe alcoholic hepatitis. Colchicine cannot be recommended for the treatment of patients with alcoholic hepatitis. PMID- 2199291 TI - Effects of ursodeoxycholic acid on gallbladder contraction and cholecystokinin release in gallstone patients and normal subjects. AB - It has been previously suggested that treatment with ursodeoxycholic acid leads to decreased gallbladder emptying. The proposed mechanism is decreased release of cholecystokinin through negative feedback control by an increased amount of intraduodenal bile acids. In the present study we examined cholecystokinin release and gallbladder contraction after oral administration of a commercial fatty meal (Sorbitract; Dagra, Diemen, The Netherlands) using ultrasonography in eight normal subjects and eight gallstone patients before and after 1 and 4 weeks of treatment with ursodeoxycholic acid (10 mg kg-1.day-1). Fasting gallbladder volume increased in 15 of 16 subjects during treatment (P less than 0.01). Minimal volume did not change. Therefore, both absolute and relative gallbladder emptying increased during therapy. Maximal decrement of gallbladder volume in milliliters and percentage as well as integrated gallbladder contraction during 90 minutes in milliliters and percentage were significantly increased after 1 and 4 weeks of treatment with ursodeoxycholic acid when compared with data before therapy. Gallstone patients tended to have larger fasting and residual gallbladder volumes than normal subjects, whereas parameters for the amount of bile expelled (maximal decrement of gallbladder volume and integrated gallbladder contraction in milliliters and percentage) did not differ. Release of cholecystokinin did not change during treatment and did not differ significantly between patients and normal subjects. Mean relative percentage of ursodeoxycholic acid in bile during treatment in 13 subjects consenting to have duodenal intubation was 47% (range 31%-60%). Changes of fasting gallbladder volume after institution of bile acid treatment correlated significantly (r = 0.74, P less than 0.01) with changes of cholesterol saturation index but not with relative percentage of ursodeoxycholic acid in bile. This study indicates that gallbladder emptying does not decrease during treatment with ursodeoxycholic acid. Moreover, there is no evidence of decreased cholecystokinin release. PMID- 2199292 TI - Bismuth therapy in gastrointestinal diseases. AB - Bismuth therapy has shown efficacy against two major gastrointestinal disorders: peptic ulcer disease and diarrhea. In peptic ulcer disease it is as effective as the H2-receptor antagonists, costs considerably less, and offers a lower rate of relapse. When Helicobacter pylori is implicated, bismuth acts as an antimicrobial agent, suppressing the organism but not eliminating it. In recent studies, bismuth compounds have been used with conventional antibiotics, producing elimination of the organism, histological improvement, and amelioration of symptoms for periods longer than one year. Bismuth subsalicylate has shown modest efficacy in treating traveler's diarrhea and acute and chronic diarrhea in children, and it is effective prophylactically for traveler's diarrhea. An epidemic of neurological toxicity was reported in France in the 1970's with prolonged bismuth treatment, usually bismuth subgallate and subnitrate. Such toxicity has been rare with bismuth subsalicylate and colloidal bismuth subcitrate. However, recent studies have demonstrated intestinal absorption of bismuth (about 0.2% of the ingested dose) and sequestration of this heavy metal in multiple tissue sites, even occurring with conventional dosing over a 6-week period. These findings have inspired recommendations that treatment periods with any bismuth-containing compound should last no longer than 6-8 weeks, followed by 8-week bismuth-free intervals. PMID- 2199293 TI - Asbestos and colorectal cancer. AB - Reports in the literature on 21 cohorts of workers exposed to asbestos were reviewed and analyzed to determine whether there is a causal association between asbestos and colorectal cancer. The latest report up to 1988 was used for each cohort. The end point was the standardized morbidity or mortality ratio as the measure of relative risk. Two additional cohorts using mortality as the end point were excluded because the authors failed to use comparable diagnostic methods for the asbestos-exposed populations and controls. The summary standardized morbidity or mortality ratio for all 21 cohorts was 0.97 (P greater than 0.05), and there was no dose-response relationship in the two studies with such data. The evidence does not meet the established criteria for making a judgment that there is a causal relationship between asbestos and colorectal cancer. PMID- 2199294 TI - Human cytochrome P450 isoforms. Their genetic heterogeneity and induction by omeprazole. PMID- 2199295 TI - Preoperative radiotherapy is better than postoperative radiotherapy in patients with rectal cancer. PMID- 2199296 TI - Release of intracellularly stored Ca2+ by inositol 1,4,5-trisphosphate--an overview. AB - 1. Inositol 1,4,5-trisphosphate (I(1,4,5)P3) releases Ca2+ from ATP-dependent Ca2+ stores in permeabilized cells and in microsomal fractions. 2. Various factors affect the amount of Ca2+ released by I(1,4,5)P3. 3. The molecular mechanism involved in the I(1,4,5)P3-induced Ca2+ release is now being investigated and I(1,4,5)P3-specific receptors and/or specific release channels are being given special attention. 4. While the I(1,4,5)P3-sensitive Ca2+ stores are presumed to locate at the endoplasmic reticulum, the relation between the I(1,4,5)P3- and the agonist-sensitive Ca2+ stores remains to be elucidated. PMID- 2199297 TI - The effects of testosterone or insulin treatment on contractile responses of the rat vas deferens following castration or streptozotocin-induced diabetes mellitus. AB - 1. Castration and streptozotocin-induced diabetes produce significant decreases in serum testosterone levels accompanied by decreased vas deferens weights, a decreased responsiveness to nerve stimulation, and altered contractile responses to carbachol and phenylephrine. 2. Treatment of castrated rats with testosterone for 8 weeks prevented the decreased vas deferens weights and contractile changes associated with castration. 3. Treatment of diabetic rats with testosterone for 8 weeks prevented the decreased vas deferens weights and the supersensitivity to contractile agonists associated with diabetes. Testosterone treatment only partially prevented the decreased response to nerve stimulation. 4. Treatment of diabetic rats with testosterone plus insulin for 8 weeks prevented the decreased vas deferens weights and decreased the sensitivity to carbachol and phenylephrine compared to controls. Testosterone plus insulin treatment prevented the decreased response to nerve stimulation. 5. There were no differences in the IC50 values for nitrendipine among any of the groups studied, suggesting that the contractile changes observed in vasa deferentia following castration or diabetes are not the result of changes in calcium movements. 6. The results suggest that decreased testosterone levels are at least partially responsible for the changes in contractility of the vas deferens of streptozotocin-diabetic rats. PMID- 2199298 TI - Simultaneous release of endothelium-derived relaxing and contracting factors induced by noradrenaline in normotensive rats. AB - 1. Noradrenaline produced a biphasic response in indomethacin (10(-5) M)-treated aorta isolated from normotensive rats. 2. The relaxation phase is enhanced by previous treatment of the animals with estrogen. 3. Blockade of the relaxant effect elicited by supramaximal concentration of noradrenaline was observed when 10(-5) M of methylene blue was present in the bathing fluid for 15 min. 4. Noradrenaline caused a simultaneous release of endothelium-derived relaxing and contracting factors in aorta from normotensive rats. PMID- 2199300 TI - Conjugative transfer of a shuttle plasmid from Escherichia coli to Mycobacterium smegmatis [corrected]. AB - The chimeric plasmid pMY10 containing the origin of replication of pAL5000, the origin of replication of pBR322, the origin of transfer of pRK2 and a kanamycin resistance gene was constructed and successfully transferred by conjugation from Escherichia coli harbouring the helper plasmid pRK4.24 into Mycobacterium smegmatis. This is the first report of conjugtive transfer of plasmid between E. coli and an acid fast organism. PMID- 2199299 TI - Does kinin mediate the hypotensive action of angiotensin converting enzyme (ACE) inhibitors? AB - The lack of kinin formation in systemic circulation and in the renal system may lead to the pathogenesis of high blood pressure (hypertension). Angiotensin converting enzyme inhibitors are able to protect the kinin inactivation by kininase II, therefore, causing an accumulation of kinin. Although the concentrations of kinin in plasma after oral administration of ACE inhibitors are conflicting this is mainly due to methodological difficulties. Kinin receptor antagonists are becoming most reliable pharmacological probes for defining the molecular actions of kinin in several physiopathological states, and in the mechanism of actions of drugs which are dependent on the kinin system. The blood pressure lowering effect of ACE inhibitors can be antagonized by the pretreatment with kinin receptor antagonists. I have therefore proposed that the hypotensive action of ACE inhibitors may reflect the activation of kinin receptor. It is suggested that the development of compounds having protective properties on the kallikrein-kinin system might be therapeutically applicable as anti-hypertensive drugs. PMID- 2199302 TI - Pathways to acetyl-CoA formation in Candida albicans. AB - The supply of acetyl units from the mitochondrion to the cytosol of Candida albicans appears to be dependent only upon the activity of carnitine acetyltransferase (CAT). The enzyme ATP:citrate lyase (ACL), the major source of acetyl units in oleaginous yeasts, is absent from C. albicans in both the mycelial and yeast forms. There appears to be no other active translocation of acetate or acetyl groups except via the action of carnitine acetyltransferase. PMID- 2199301 TI - Biochemical and genetic analysis of an alpha-mannosidase mutant from Saccharomyces cerevisiae. AB - A yeast mutant lacking non-specific alpha-mannosidase activity was found as a background marker during our search for dap2 mutants (Suarez-Rendueles, P. and Wolf, D. H. (1987) J. Bacteriol. 169, 4041-4048). The mutant (DPS-15) is characterized in detail. The mutation called amd1 segregates 2:2 in meiotic tetrads, indicating a single chromosomal gene mutation which is recessive. Diploids heterozygous for amd1 show gene dosage. Thus, it appears that AMD1 might be the structural gene for alpha-mannosidase. Results obtained with this mutant show that alpha-mannosidase is not a vital component of the vegetative cell cycle. The differentiation process of sporulation is not disturbed in homozygous mutant diploids. Mannose turnover does not seem to be altered in mutant cells. PMID- 2199303 TI - HEp-2 cell adherence and Vero cell cytotoxin production by EPEC strains isolated from children with diarrhoea in New Zealand. AB - A total of 112 EPEC strains isolated from children with diarrhoea in New Zealand were examined for mannose-resistant HEp-2 cell adherence and production of exotoxins. Enterotoxin production was not detected in any of the strains examined. Verotoxin production was detected in 13 (11.6%) strains and of these 4 were also found to adhere to HEp-2 cells. HEp-2 cell adherence was displayed by a total of 29 (25.8%) strains of which 22 were diffusely adherent. Only 3 (2.7%) strains were shown to belong to the new virulence phenotype, entero-aggregative adherence, when examined in the adherence assay. We identified one strain with the novel characteristic of causing detachment of HEp-2 cells from glass coverslips and are further investigating this possible virulence mechanism. These results suggest that if EPEC strains are to be considered as a cause of diarrhoea, the search for new virulence factors must be extended. PMID- 2199304 TI - Acid shock proteins of Escherichia coli. AB - Synthesis of total cellular proteins of Escherichia coli was studied after transfer of cultures from pH 6.9 to pH 4.3. Proteins induced by such an external pH shift down were identified by mono- and bi-dimensional electrophoresis. 30 to 45 min after an acid shift, a group of at least sixteen polypeptides was markedly induced. Four of these polypeptides corresponded to the well known heat shock proteins GroEL, DnaK, HtpG and HtpM. Their pH induction was RpoH-dependent. Three other pH-induced proteins were previously identified as stress proteins induced either by osmolarity or aerobiosis or low temperature (proteins 32 (defined in this paper), C70.0 and C62.7). Seven other proteins were specifically induced after an acid shift and were called acid shock proteins (ASP). The induction of one of these proteins was RpoH-dependent, whereas that of others was RpoH independent. PMID- 2199305 TI - Analysis of OmpC-beta-lactamase hybrid proteins: OmpC appears not to contain discrete localization signals. AB - Fusions to the beta-lactamase (bla) gene were employed to analyze the presence of localization information in the mature part of OmpC, a major pore-forming outer membrane protein in Escherichia coli K-12. Six translational ompC-bla gene fusions were constructed, the shortest of them containing only part of the ompC signal sequence and the largest approximately 90% of the sequence encoding mature OmpC protein. Export of the hybrid proteins to a non-cytoplasmic location was a prerequisite for ampicillin resistance. Localization of the hybrid proteins by cell fractionation and solid phase iodination of whole cells suggested that the exported hybrid proteins possibly interacted with the outer membrane in vivo. No specific sequence of the mature OmpC protein, however, was found to promote this interaction. PMID- 2199306 TI - A comparison of HEp-2 cell invasion by enteropathogenic and enteroinvasive Escherichia coli. AB - In order to further characterize cellular invasion by enteropathogenic Escherichia coli (EPEC), we compared invasion of HEp-2 cells by EPEC and enteroinvasive E. coli (EIEC). We used a gentamicin HEp-2 cell assay and measured bacterial recovery under conditions of varying incubation time and temperature, and in the presence or absence of inhibitors of cellular microfilaments and microtubules. We found that, unlike EIEC, EPEC did not rapidly multiply within HEp-2 cell but invaded well at 32 degrees C. While microfilament inhibitors reduced invasion by both EIEC and EPEC, microtubule inhibitors reduced invasion by EPEC only. These results suggest that EPEC and EIEC differ in their mechanisms of epithelial cell invasion. PMID- 2199307 TI - L. C. Dunn and mouse genetic mapping. PMID- 2199308 TI - Physical analysis of spontaneous and mutagen-induced mutants of Escherichia coli K-12 expressing DNA exonuclease VIII activity. AB - We have mapped the extents of two deletion sbcA mutations which result in production of DNA exonuclease VIII (ExoVIII). One mutation, sbcA8, deletes about 140 kb of DNA which includes most of the Rac prophage and the trg gene. Western blot analysis shows that the protein produced is larger than wild type ExoVIII. The nucleotide sequence shows that a translational gene fusion has occurred. The N-terminal 294 codons of recE have been deleted and the remaining C-terminal codons have been fused to the N-terminal portion of another reading frame we call sfcA. Analysis of the protein sequence encoded by sfcA shows an 83% similarity with rat and mouse NADP-linked malic enzyme. We discuss the possibility that sfcA is identical to maeA which encodes NAD-linked malic enzyme from Escherichia coli. Restriction nuclease analysis of a second deletion, sbcA81, by Southern blot technique indicates that about 105 kb of DNA have been deleted and a transcriptional gene fusion has occurred between recE and the regulatory region of an E. coli chromosomal gene. We also examined eight other sbc mutations that result in ExoVIII production. Five have no effect on restriction nucleotide fragment sizes detected by complementarity to lambda rev as probe. These are presumed point mutations. Three seem to produce additional restriction nucleotide fragments complementary to lambda rev. The possible nature of these sbc mutations is discussed. PMID- 2199309 TI - A set of lacZ mutations in Escherichia coli that allow rapid detection of specific frameshift mutations. AB - We have used site-directed mutagenesis to alter bases in lacZ near the region encoding essential residues in the active site of beta-galactosidase. The altered sequences generate runs of six or seven identical base pairs which create a frameshift, resulting in a Lac- phenotype. Reversion to Lac+ in each strain can occur only by a specific frameshift at these sequences. Monotonous runs of A's (or of T's on the opposite strand) and G's (or C's) have been constructed, as has an alternating -C-G- sequence. These specific frameshift indicator strains complement a set of six previously described strains which detect each of the base substitutions. We have examined a variety of mutagens and mutators for their ability to cause reversion to Lac+. Surprisingly, frameshifts are well stimulated at many of these runs by ethyl methanesulfonate, N-methyl-N'-nitro-N nitrosoguanidine and 2-amino-purine, mutagens not widely known to induce frameshifts. A comparison of ethyl methanesulfonate, N-methyl-N'-nitro-N nitrosoguanidine and 2-aminopurine frameshift specificity with that found with a mutH strain suggests that these mutagens partially or fully saturate or inactivate the methylation-directed mismatch repair system and allow replication errors leading to frameshifts to escape repair. This results in a form of indirect mutagenesis, which can be detected at certain sites. PMID- 2199310 TI - Analysis of the GAL3 signal transduction pathway activating GAL4 protein dependent transcription in Saccharomyces cerevisiae. AB - The Saccharomyces cerevisiae GAL/MEL regulon genes are normally induced within minutes of galactose addition, but gal3 mutants exhibit a 3-5-day induction lag. We have discovered that this long-term adaptation (LTA) phenotype conferred by gal3 is complemented by multiple copies of the GAL1 gene. Based on this result and the striking similarity between the GAL3 and GAL1 protein sequences we attempted to detect galactokinase activity that might be associated with the GAL3 protein. By both in vivo and in vitro tests the GAL3 gene product does not appear to catalyze a galactokinase-like reaction. In complementary experiments, Escherichia coli galactokinase expressed in yeast was shown to complement the gal1 but not the gal3 mutation. Thus, the complementation activity provided by GAL1 is not likely due to galactokinase activity, but rather due to a distinct GAL3-like activity. Overall, the results indicate that GAL1 encodes a bifunctional protein. In related experiments we tested for function of the LTA induction pathway in gal3 cells deficient for other gene functions. It has been known for some time that gal3gal1, gal3gal7, gal3gal10, and gal3 rho- are incapable of induction. We constructed isogenic haploid strains bearing the gal3 mutation in combination with either gal15 or pgi1 mutations: the gal15 and pgi1 blocks are not specific for the galactose pathway in contrast to the gal1, gal7 and gal10 blocks. The gal3gal5 and gal3pgi1 double mutants were not inducible, whereas both the gal5 and pgi1 single mutants were inducible. We conclude that, in addition to the GAL3-like activity of GAL1, functions beyond the galactose specific GAL1, GAL7 and GAL10 enzymes are required for the LTA induction pathway. PMID- 2199311 TI - ret1-1, a yeast mutant affecting transcription termination by RNA polymerase III. AB - In eukaryotes, extended tracts of T residues are known to signal the termination of RNA polymerase III transcription. However, it is not understood how the transcription complex interacts with this signal. We have developed a selection system in yeast that uses ochre suppressors weakened by altered transcription termination signals to identify mutations in the proteins involved in termination of transcription by RNA polymerase III. Over 7600 suppression-plus yeast mutants were selected and screened, leading to the identification of one whose effect is mediated transcriptionally. The ret1-1 mutation arose in conjunction with multiple rare events, including uninduced sporulation, gene amplification, and mutation. In vitro transcription extracts from ret1-1 cells terminate less efficiently at weak transcription termination signals than those from RET1 cells, using a variety of tRNA templates. In vivo this reduced termination efficiency can lead to either an increase or a further decrease in suppressor strength, depending on the location of the altered termination signal present in the suppressor tRNA gene. Fractionation of in vitro transcription extracts and purification of RNA polymerase III has shown that the mutant effect is mediated by highly purified polymerase in a reconstituted system. PMID- 2199312 TI - TRK2 is required for low affinity K+ transport in Saccharomyces cerevisiae. AB - TRK1, the gene encoding the high affinity K+ transporter in Saccharomyces cerevisiae, is nonessential due to the existence of a functionally independent low affinity transporter. To identify the gene(s) encoding the low affinity K+ transporter, we screened trk1 delta cells for mutants (Kla-) that require higher concentrations of K+ in the medium to support growth. trk1 delta trk2 mutants require up to tenfold higher concentrations of K+ to exhibit normal growth compared to trk1 delta TRK2 cells. K+ and 86Rb+ transport assays demonstrate that the mutant phenotype is due to defective K+ transport (uptake). Each of 38 independent mutants contains a mutation in the same gene, TRK2. Cells deficient for both high and low affinity K+ transport (trk1 delta trk2) exhibit hypersensitivity to low extracellular pH that can be suppressed by high concentrations of K+ but not Na+. TRK1 completely suppresses both the K+ transport defect and low pH hypersensitivity of trk2 cells, suggesting that TRK1 and TRK2 are functionally independent. PMID- 2199313 TI - Direct selection for mutants with increased K+ transport in Saccharomyces cerevisiae. AB - Saccharomyces cerevisiae cells containing a deletion of TRK1, the gene encoding the high affinity potassium transporter, retain only low affinity uptake of this ion and consequently lose the ability to grow in media containing low levels (0.2 mM) of potassium. Using a trk1 delta strain, we selected spontaneous Trk+ pseudorevertants that regained the ability to grow on low concentrations of potassium. The revertants define three unlinked extragenic suppressors of trk1 delta. Dominant RPD2 mutations and recessive rpd1 and rpd3 mutations confer increased potassium uptake in trk1 delta cells. Genetic evidence suggests that RPD2 mutations are alleles of TRK2, the putative low affinity transporter gene, whereas rpd1 and rpd3 mutations increase TRK2 activity: (1) RPD2 mutations are closely linked to trk2, and (2) trk2 mutations are epistatic to both rpd1 and rpd3. rpd1 maps near pho80 on chromosome XV and rpd3 maps on the left arm of chromosome XIV, closely linked to kre1. PMID- 2199314 TI - Extragenic suppressors of mar2(sir3) mutations in Saccharomyces cerevisiae. AB - The silent mating-type genes (HML and HMR) of Saccharomyces cerevisiae are kept under negative transcriptional control by four trans-acting MAR (or SIR) loci. We have isolated extragenic suppressors of the mar2-1 mutation which, based on genetic complementation tests, define two additional loci involved in regulating the expression of HML and HMR. A strain with the genotype HMLa MAT alpha HMRa mar2-1 is sterile due to the simultaneous expression of a and alpha information. Two mutants exhibiting an alpha phenotype (which may result from the restoration of MAR/SIR repression) were isolated and genetically characterized. The mutations in these strains: (1) are recessive, (2) are capable of suppressing a mar2 deletion mutation, (3) are unlinked to MAT, (4) complement one another as well as the previously identified sum1-1 mutation, and (5) are not new alleles of the known MAR/SIR loci. We designate these new regulatory loci SUM2 and SUM3 (suppressor of mar). Unlike the sum1-1 mutation, suppression by sum2-1 and sum3-1 is mar2-locus specific. Both sum2-1 and sum3-1 affect the expression of a information at the HM loci. Transcript analysis shows a significant reduction in HMLa and HMRa gene transcription in mar2-1 sum2-1 and mar2-1 sum3-1 cells. Furthermore, we have found genetic evidence to suggest that mar2-1 sum2-1 cells exhibit only partial expression of silent alpha information. We conclude that the SUM2 and SUM3 gene products are required for expression of the HM loci and act downstream of the MAR2 (SIR3) gene function. Possible mechanisms for the action of the SUM gene products are discussed. PMID- 2199315 TI - Chromosomal assignment of mutations by specific chromosome loss in the yeast Saccharomyces cerevisiae. AB - Yeast 2-microns plasmids were integrated near the centromere of a different chromosome in each of 16 cir0 mapping strains of Saccharomyces cerevisiae. The specific chromosomes containing the integrated 2-microns plasmid DNA were lost at a high frequency after crossing the cir0 strains to cir+ strains. A recessive mutation in a cir+ strain can then be easily assigned to its chromosome using this set of mapping strains, since the phenotype of the recessive mutation will be manifested only in diploids having the integrated 2-microns plasmid and the unmapped mutation on homologous chromosomes. PMID- 2199317 TI - The role of similarity and difference in fungal mating. PMID- 2199316 TI - Cloning of the DNA repair gene, uvsF, by transformation of Aspergillus nidulans. AB - As a first step in the cloning of the DNA repair gene uvsF of Aspergillus nidulans, uvsF pyrG double mutant strains were transformed with a genomic library which carried the complementing Neurospora pyr-4 gene in the vector. Rare pyr+ uvs+ cotransformants were obtained on media lacking pyrimidines, overlayed with MMS (methyl-methane sulfonate) to which uvsF is hypersensitive. Among MMS resistant transformants, Southerns revealed two types which showed single bands of different sizes when BglII-digested genomic DNA was probed with the vector. Both types produced uvsF- recombinants without vector sequences in homozygous crosses, but only those with the larger band also produced haploid uvs+ progeny. Using BglII-digested genomic DNA to transform Escherichia coli, plasmids of the corresponding two sizes could be rescued. Their inserts had a short internal region in common, giving evidence of rearrangement(s). In secondary transformation of uvsF mutants, only the plasmids with the larger insert showed complementation and these were used to screen Aspergillus libraries. Three types of genomic and two overlapping cDNA clones were identified. The cDNAs hybridized not only to each other, but also to the common region of the rescued plasmids. Therefore, cDNA subclones were used to map the putative uvsF sequences to a short segment in one genomic clone. In Northerns, the complementing large plasmid hybridized to three mRNAs, while the cDNA subclone identified one of these as the probable uvsF message. PMID- 2199318 TI - Mixed segregation of chromosomes during single-division meiosis of Saccharomyces cerevisiae. AB - Normal meiosis consists of two consecutive cell divisions in which all the chromosomes behave in a concerted manner. Yeast cells homozygous for the mutation cdc5, however, may be directed through a single meiotic division of a novel type. Dyad analysis of a cdc5/cdc5 strain with centromere-linked markers on four different chromosomes has shown that, in these meioses, some chromosomes within a given cell segregate reductionally whereas others segregate equationally. The choice between the two types of segregation in these meioses is made individually by each chromosome pair. Different chromosome pairs exhibit different segregation tendencies. Similar results were obtained for cells homozygous for cdc14. PMID- 2199319 TI - Centromeric regions control autonomous segregation tendencies in single-division meiosis of Saccharomyces cerevisiae. AB - We have previously shown that yeast cdc5 or cdc14 homozygotes can be led through a single-division meiosis in which some of the chromosomes segregate reductionally whereas others, within the same cell, segregate equationally. Chromosomes XI tend to segregate reductionally, whereas chromosomes IV tend to segregate equationally. In this report we present experiments with cdc5 homozygous strains, in which the centromeres of one or both chromosomes XI was replaced by the centromeric region from chromosome IV. Analysis of the products of single-division meioses in these strains demonstrates that the choice between reductional or equational segregation is directed by sequences in the vicinity of the centromeres. Although the choice is made separately for each individual chromosome, the analysis also reveals the existence of a system responsible for coordinated segregation of the two chromosomes of a given pair. PMID- 2199320 TI - Two genes differentially regulated in the cell cycle and by DNA-damaging agents encode alternative regulatory subunits of ribonucleotide reductase. AB - Ribonucleotide reductase activity is essential for progression through the cell cycle, catalyzing the rate-limiting step for the production of deoxyribonucleotides needed for DNA synthesis. The enzymatic activity of the enzyme fluctuates in the cell cycle with an activity maximum in S phase. We have identified and characterized two Saccharomyces cerevisiae genes encoding the regulatory subunit of ribonucleotide reductase, RNR1 and RNR3. They share approximately 80% amino acid identity with each other and 60% with the mammalian homolog, M1. Genetic disruption reveals that the RNR1 gene is essential for mitotic viability, whereas the RNR3 gene is not essential. A high-copy-number clone of RNR3 is able to suppress the lethality of rnr1 mutations. Analysis of mRNA levels in cell-cycle-synchronized cultures reveals that the RNR1 mRNA is tightly cell-cycle regulated, fluctuating 15- to 30-fold, and is coordinately regulated with the POL1 mRNA, being expressed in the late G1 and S phases of the cell cycle. Progression from the alpha-factor-induced G1 block to induction of RNR1 mRNA is blocked by cycloheximide, further defining the requirement for protein synthesis in the G1- to S-phase transition. Both RNR1 and RNR3 transcripts are inducible by treatments that damage DNA, such as 4-nitroquinoline 1-oxide and methylmethanesulfonate, or block DNA replication, such as hydroxyurea. RNR1 is inducible 3- to 5-fold, and RNR3 is inducible greater than 100-fold. When MATa cells are arrested in G1 by alpha-factor, RNR1 and RNR3 mRNA is still inducible by DNA damage, indicating that the observed induction can occur outside of S phase. Inhibition of ribonucleotide reductase activity by hydroxyurea treatment results in arrest of the cell cycle in S phase as large budded, uninucleate cells. This specific cell-cycle arrest is independent of the RAD9 gene, defining a separate pathway for the coordination of DNA synthesis and cell-cycle progression. PMID- 2199321 TI - A yeast H2A-H2B promoter can be regulated by changes in histone gene copy number. AB - The two divergently transcribed H2A-H2B gene pairs in yeast are differentially regulated as a function of the copy number of histone genes. Transcription of an HTA2-lacZ reporter gene is independent of histone gene copy number. Transcription of an HTA1-lacZ gene can be repressed or derepressed, depending on the number of HTA plus HTB genes in cells. Regulation by histone gene dosage is dependent on a negative site in the HTA1-HTB1 promoter and the products of regulatory genes that act through this site. The level of H2A plus H2B protein in the cell may signal the response to histone gene copy number, suggesting that transcription of the HTA1-HTB1 locus can be autogenously regulated. This phenomenon may be used, in part, to maintain the balanced synthesis of histones, a critical parameter in nucleosome assembly. PMID- 2199322 TI - Escherichia coli RNase E has a role in the decay of bacteriophage T4 mRNA. AB - Bacteriophage T4 mRNAs are markedly stabilized, both chemically and functionally, in an Escherichia coli strain deficient in the RNA-processing endonuclease RNase E. The functional stability of total T4 messages increased 6-fold; we were unable to detect a T4 message whose functional stability was not increased. There was a 4-fold increase in the chemical stability of total T4 RNA. The degree of chemical stabilization of six specific T4 mRNAs examined varied from a maximum of 28-fold to a minimum of 1.5-fold. In the RNase E-deficient strain, several minutes delay and a slower rate of progeny production led to a reduction in final phage yield of approximately 50%. Although the effect of the rne temperature-sensitive mutation could be indirect, the simplest interpretation of our results is that RNase E acts directly in the degradation of many T4 mRNAs. PMID- 2199323 TI - Protein polymorphism and genetic distance in South American cricetid rodents of the genus Calomys. AB - Allozymic variation in population samples of Calomys laucha, C. musculinus and C. venustus collected simultaneously from the province of Cordoba, Argentina, was analyzed by gel electrophoresis. These three species showed high levels of polymorphism: for C. laucha, the P value was 72.7% and the H value was 0.147 (19 loci); for C. musculinus, P = 61.9% and H = 0.149 (20 loci); for C. venustus, P = 66.7% and H = 0.146 (18 loci). These species are non-fossorial generalists, have a high reproductive rate and live in disturbed habitats. The similarity indices (S) range between 0.613 and 0.681. On the basis of genetic distance, D (between 0.354 and 0.476), divergence time was estimated to be from 6.3 to 8.5 million years (late Miocene). Even admitting some imprecision for this estimate, the remarkable differences at the structural gene level shown by the species analyzed, suggest they had an early origin. PMID- 2199324 TI - Transcriptional control by galactose of a yeast gene encoding a protein homologous to mammalian aldo/keto reductases. AB - Expression of the S. cerevisiae gene, GCY, encoding a 35-kDa protein with striking homology to mammalian aldo/keto reductases, is under the control of galactose: the intracellular concentration of the respective mRNA (about 1300 nt in length) varies strongly with the carbon source. It is particularly high when galactose is the sole energy source but is low as soon as glucose is present. Lactate, glycerol and raffinose lead to intermediate expression. Both Northern blot analyses and lacZ fusion data indicate a 20- to 50-fold increase in the steady state concentrations of mRNA and beta Gal activity, respectively, when grown on galactose as compared to glucose. The gene is derepressed after cultivation on glycerol in the wt and in a gal80 mutant background but remains uninducible by galactose in strains carrying either a gal2 or a gal4 mutation, affecting galactose permease and the GAL gene trans-activator, respectively. Analysis of GCY expression in gal regulatory mutants reveals epistasis interactions of the gal4 and the gal80 mutations as expected if GCY is regulated by the Gal control system. Repression of GCY transcription by glucose is observed in all three above gal mutant strains. The results suggest that the gene is both positively controlled by galactose and negatively by glucose. Analysis of a set of upstream deletions identifies a single UAS matching the consensus for GAL gene upstream regulation sites. By contrast to other genes regulated by galactose, disruption mutants of GCY exhibit no obvious phenotype, and in particular do not lose the ability to grow on and adapt to galactose. Enzyme tests with AKR specific substrates suggest that GCY encodes a carbonyl reductase. PMID- 2199325 TI - Functional expression of the Candida albicans beta-tubulin gene in Saccharomyces cerevisiae. AB - Expression of the beta-tubulin-encoding gene (TUB2) of Candida albicans has been examined in Saccharomyces cerevisiae. Overexpression of the TUB2 gene of C. albicans, as well as that of S. cerevisiae, was found to be lethal. Chromosomal integration of the C. albicans TUB2 gene into a strain in which the native TUB2 gene had been deleted led to functional complementation. The results demonstrate that correct splicing of the two introns present in the C. albicans TUB2 gene occurs in the heterologous host strain containing this gene. Such strains are supersensitive to the tubulin-binding agent benomyl, indicating that the natural resistance of C. albicans to benomyl is not related to the structure of its beta tubulin. PMID- 2199326 TI - Construction of Escherichia coli vectors for expression and mutagenesis: synthesis of human c-Myc protein that is initiated at a non-AUG codon in exon 1. AB - Three types of Escherichia coli vector for both gene expression and mutagenesis were constructed from a plasmid/phage chimera vector pUC118. Each vector contains the lac (pTD-lac), tac (pTD-tac), or T7 promoter (pTD-T7). Downstream from the promoter, these vectors have sequences in common, including a Shine-Dalgarno (SD), multiple cloning sequence, sequence-primer binding site, transcription termination signal, and M13 origin of replication. Using single-stranded circular DNA obtained by infection with helper phage, oligodeoxyribonucleotide (oligo) directed mutagenesis allows the appropriate fusion between the vector SD sequence and the start codon in the inserted fragment. Since a complementary oligo representing a large deletion is generally used for this construction, the extra nucleotides in the opposing strand form a loop structure. Thus, we have designated this mutagenesis as 'loop-out mutagenesis'. Expression plasmid encoding the larger human c-Myc protein that is initiated at a non-AUG codon in exon 1 and its derivatives were constructed using a pTD-T7 vector. Expression experiments indicated that the wild-type (wt) protein was synthesized poorly after induction with isopropyl-beta-D-thiogalactopyranoside, while one of the derivatives, p62M1T, in which a threonine residue was added at the N terminus of the wt protein, was produced in a large quantity in E. coli. PMID- 2199327 TI - Construction of broad-host-range vectors for the selection of divergent promoters. AB - A series of promoter-probe plasmid vectors has been constructed which allows for the selection of DNA sequences containing divergent control elements. Each vector contains a pair of promoterless genes [encoding beta-galactosidase (lacZ), alkaline phosphatase (phoA), and bacterial luciferase (luxAB)] arranged in an antiparallel fashion and separated by a large intervening multiple cloning site. The vectors permit direct detection of promoter activity on indicator plates after transformation. Cloned promoters are selected based on production of coloured products in the case of lacZ and phoA, and by the emission of light in the case of luxAB. These vectors have been tested using known divergent promoter elements from pBR322 and Pseudomonas phage D3. PMID- 2199328 TI - Cloning of genes involved in erythromycin biosynthesis from Saccharopolyspora erythraea using a novel actinomycete-Escherichia coli cosmid. AB - Two plasmids were constructed that replicate in Saccharopolyspora (Sac.) erythraea, Escherichia coli and Streptomyces (S.) lividans, and used for the cloning of a locus involved in the synthesis of the macrolide antibiotic erythromycin (Er). Plasmid pAL7002 contains the thiostrepton-resistance gene (tsr), a replicon-containing fragment from pJVI and pUC9. Plasmid pNJI contains the lambda cos site but is otherwise similar to pAL7002. A library of total DNA from Sac. erythraea was constructed in pNJI and probed in colony hybridizations with a DNA fragment containing ermE, the Sac. erythraea ErR-encoding gene. Plasmids obtained were subsequently introduced into EryA mutants of Sac. erythraea blocked in synthesis of Er (Ery-) and transformants were screened for restoration of Er production (Ery+). Several plasmids were found to convert two mutants to Ery+, but a third EryA strain could not be restored to Ery+ by any of the plasmids employed. A 5-kb segment, designated eryAI, responsible for restoring the Ery+ phenotype in the EryA strains, was identified and mapped in the segment 12 to 17 kb downstream from ermE. Gene disruption experiments indicated that the 5-kb length of eryAI is fully internal to an eryAI-containing transcript. In Southern blots it was shown that one of the EryA strains carried a small deletion in eryAI and that, in at least some of the transformants restored to Ery+, the deletion had been replaced by the wild-type eryAI allele.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2199329 TI - Cloning and characterization of the histidine biosynthetic gene cluster of Streptomyces coelicolor A3(2). AB - Biochemical and genetic data indicate that in Streptomyces coelicolor A3(2) the majority of the genes involved in the biosynthesis of histidine are clustered in a small region of the chromosome [Carere et al., Mol. Gen. Genet. 123 (1973) 219 224; Russi et al., Mol. Gen. Genet. 123 (1973) 225-232]. To investigate the structural organization and the regulation of these genes, we have constructed genomic libraries from S. coelicolor A3(2) in pUC vectors. Recombinant clones were isolated by complementation of an Escherichia coli hisBd auxotroph. A recombinant plasmid containing a 3.4-kb fragment of genomic DNA was further characterized. When cloned in the plasmid vector, pIJ699, this fragment was able to complement S. coelicolor A3(2) hisB mutants. Overlapping clones spanning a 15 kb genomic region were isolated by screening other libraries with labeled DNA fragments obtained from the first clone. Derivative clones were able to complement mutations in four different cistrons of the his cluster of S. coelicolor A3(2). Nucleotide sequence analysis of a 4-kb region allowed the identification of five ORFs which showed significant homology with the his gene products of E. coli. The order of the genes in S. coelicolor A3(2) (5'--hisD-hisC hisBd-hisH-hisA-3') is the same as in the his operon of E. coli. PMID- 2199330 TI - Escherichia coli and Saccharomyces cerevisiae acetylornithine aminotransferase: evolutionary relationship with ornithine aminotransferase. AB - Genes argD and ARG8, encoding the acetylornithine aminotransferase (ACOAT) subunit in Escherichia coli and Saccharomyces cerevisiae, respectively, have been cloned and sequenced. The deduced amino acid sequences show substantial similarity. Moreover, they resemble ornithine aminotransferase (OAT) sequences (i.e., those from yeast, rat and man); the observed similarities are statistically significant, indicating that the enzymes are homologous. However, in contrast to OATs, which appear to be substrate (i.e., ornithine)-specific, S. cerevisiae ACOAT transaminates ornithine about as efficiently as E. coli does. The evolutionary relationship between ACOATs and OATs is discussed in terms of substrate ambiguity. PMID- 2199331 TI - Efficient expression of the Saccharomyces cerevisiae glycolytic gene ADH1 is dependent upon a cis-acting regulatory element (UASRPG) found initially in genes encoding ribosomal proteins. AB - The glycolytic form of alcohol dehydrogenase (ADHI) is encoded by the ADH1 gene of Saccharomyces cerevisiae. We found that efficient expression of the ADH1 gene requires a sequence between bp -635 and -615 with respect to the +1 mRNA start point; removal of this sequence reduced ADH1 mRNA levels 25-fold but did not affect carbon-source regulation. DNaseI footprinting analysis of the ADH1 promoter revealed the specific protection of a perfect match to UASRPG at -630 to -615. UASRPG is thought to be responsible for activation of transcription, via binding of the translation upstream factor (TUF), of genes encoding components of the translational apparatus. In band retardation assays, the promoters for the elongation factor 1 alpha-encoding genes (TEF1 and TEF2) competed for binding of the protein to the copy of UASRPG in the ADH1 promoter. We conclude that TUF is probably involved in activation of the bulk of ADH1 transcription. Further, we propose that TUF has a role in the activation of many or most glycolytic genes. If so, it is essential for efficient expression of a wide variety of functionally disparate products that are required by yeast cells for rapid growth. PMID- 2199332 TI - Isolation of a novel protein kinase-encoding gene from yeast by oligodeoxyribonucleotide probing. AB - We have identified a novel protein kinase-encoding gene, KIN3, in the genome of the budding yeast Saccharomyces cerevisiae. The gene was isolated from a library of cloned genomic fragments by probing with an oligodeoxyribonucleotide mixture corresponding to part of a highly-conserved region in the catalytic domain of protein serine-threonine kinases. KIN3 is unique in the yeast genome, maps to chromosome VI and is actively expressed in mitotically dividing cells to produce a 1400 nucleotide (nt) message. The nt sequence of KIN3 predicts a protein product of 43.4 kDa which contains all of the conserved elements found in known protein serine-threonine kinases, although the organisation of these elements in the KIN3 gene product differs significantly from the consensus. The function of the KIN3-encoded protein kinase is unclear although it appears not to be essential for growth, conjugation or sporulation. PMID- 2199333 TI - Isolation and sequence analysis of CDC43, a gene involved in the control of cell polarity in Saccharomyces cerevisiae. AB - The Saccharomyces cerevisiae CDC43 gene product is involved in establishing cell polarity during the cell-division cycle. When grown at restrictive temperatures, temperature-sensitive cdc43 mutants are unable to form buds and display delocalized cell-surface deposition [Adams et al., J. Cell Biol. (1990) in press]. We have isolated a cdc43-complementing plasmid from a yeast genomic-DNA library and localized the CDC43 gene, by subcloning and transposon-mutagenesis experiments, to a 1.2-kb region of DNA that contained only one significant ATG initiated open reading frame of 213 codons. The putative CDC43 gene product contains a possible nuclear-localization signal sequence, a cysteine-rich domain and a histidine-rich domain, and a region that is similar in structure to alpha helix-turn-alpha-helix structural domains present in some prokaryotic and eukaryotic DNA-binding proteins. PMID- 2199334 TI - Nucleotide sequence and characterization of temperature-sensitive pol1 mutants of Saccharomyces cerevisiae. AB - We have analyzed the effects of temperature-sensitivity (ts)-conferring mutations in the Saccharomyces cerevisiae DNA polymerase I-encoding gene on cell growth, in vivo DNA synthesis, intrachromosomal gene conversion and pop-out recombination. Also, we have identified the molecular defect responsible for the ts phenotype. Two mutant alleles (cdc17-1, cdc17-2) were originally identified as cell-cycle mutations, while a third mutation (hpr3) was found during a genetic screening for mutants with a hyper-recombination phenotype. Both cdc17-2 and hpr3 cells complete one round of cell division and DNA replication after shift to nonpermissive temperature, before being arrested as dumbbell-shaped cells. Conversely, the cdc17-1 mutation immediately blocks growth and DNA synthesis at 37 degrees C. No substantial difference was observed in the frequency of intrachromosomal gene conversion and pop-out recombination events, when hpr3 and cdc17-1 were compared to the previously characterized pol1-1 mutant. These two frequencies were ten- to 30-fold above wild-type level at semipermissive temperature. In each mutant, a single bp substitution, causing the replacement of Gly residues by either Asp (cdc17-1, cdc17-2) or Glu (hpr3) in yeast DNA polymerase I is responsible for the ts phenotype. PMID- 2199335 TI - Cutaneous signs of internal disease in the elderly. AB - The elderly are prone to several systemic diseases that have their own particular cutaneous markers. These include pruritus, pigmentary changes, and the various manifestations associated with diabetes mellitus, among others. Physician recognition of the cutaneous signs of internal disorders will prompt early diagnosis and prompt treatment of the primary disease. PMID- 2199336 TI - Injuries in the elderly: evaluation and initial response. AB - The injured elderly patient presents a special challenge to the treating physician; there tends to be less margin for error than in younger patients and a greater chance that mortality will result. Beyond the general need for rapid assessment of an often complicated situation, there are specific evaluative and therapeutic techniques, system-by-system and organ-by-organ, that can help expedite the patient's recovery. Guidelines for ICU admission and possible withholding of care are also suggested. PMID- 2199337 TI - A physician's guide to coordinating oral health and primary care. AB - Knowledge of specific issues of mutual concern and clear communication between primary care physicians and dentists are of special importance for the safe dental treatment of elderly patients. This article reviews the medical-dental management of patients at risk for infective endocarditis, late prosthetic joint infection, excessive bleeding due to anticoagulants, and complications from ischemic heart disease. Behavior management of mentally impaired individuals who are resistant or combative during dental treatment is also discussed. PMID- 2199338 TI - Meningitis as it presents in the elderly: diagnosis and care. AB - The clinical presentation of bacterial meningitis in the elderly is often more subtle than in younger patients. Delay in diagnosis and treatment contributes significantly to morbidity and mortality. The presence of fever and a change in mental status in an elderly patient should raise suspicion for the presence of meningitis and prompt examination of the cerebrospinal fluid. Knowledge of the bacterial pathogens causing meningitis in this age group and administration of the recommended antimicrobial agents can greatly reduce morbidity and neurologic sequelae. This review updates the primary care physician in the diagnosis and management of this serious infection. PMID- 2199339 TI - [Observations on Roman medicine]. AB - How far are we entitled to speak of Roman medicine at all? After the arrival of Greek medicine at Rome, the genuine medicine of the earlier Romans, the only one that may be qualified as authentically Roman, survived in rural areas only. Otherwise, medicine in Rome and her Empire was Greek by language and doctrine as well as by its practitioners. Nevertheless, there exists an important medical literature in Latin. Although its inspiration, its sources and its models are Greek, this literature reveals, here and there, the intention to bend that medicine imported from Greece towards the Roman medicine of the old times. It shows, too, a certain reshaping of the Greek substance according to specific Roman elements. This paper, which is just the beginning of a broader investigation, is based on the major work of Latin medical literature, i. e. Celsus's De medicina. PMID- 2199340 TI - [Charles Durand, Charles Daremberg and Gerard Marchant, or the patient, the historian of medicine and the psychiatrist]. AB - Between 1850 and 1870, a pathetic patient by the name of Charles Durand meets the famous historian of medicine Charles Daremberg and the dedicated psychiatrist Georges Marchant. Thus, relying upon every day life events, the authors tell the story of French psychiatry for the generation that came after the 1838 law on Mental Patient Care. PMID- 2199341 TI - [Luigi Belloni. 1914-1989]. PMID- 2199342 TI - Effects of paraquat on cultures of Escherichia coli: turbidity versus enumeration. AB - The dioxygen-dependent toxicity of paraquat has been studied both in terms of its effects on growth, monitored as increases in turbidity, and on viability, measured by plating and counting of colonies. In the absence of paraquat, turbidity and enumeration increased in parallel. However, in the presence of paraquat, turbidity increased for several hours even while enumeration indicated a marked decrease in viability. The basis for this apparent discrepancy is continued increase in size of individual cells, which have stopped dividing and are losing viability under the influence of paraquat. It can evidently be misleading to study the effects of paraquat on microorganisms in terms of changes in turbidity. PMID- 2199343 TI - Mechanisms for regulating oxygen toxicity in phytophagous insects. AB - The antioxidant enzymatic defense of insects for the regulation of oxygen toxicity was investigated. Insect species examined were lepidopterous larvae of the cabbage looper (Trichoplusia ni), southern armyworm (Spodoptera eridania), and black swallowtail (Papilio polyxenes). These phytophagous species are subject to both endogenous and exogenous sources of oxidative stress from toxic oxygen radicals, hydrogen peroxide (H2O2) and lipid peroxides (LOOH). In general, the constitutive levels of the enzymes superoxide dismutase (SOD), catalase (CAT), glutathione transferase (GT), and its peroxidase activity (GTpx), and glutathione reductase (GR), correlate well with natural feeding habits of these insects and their relative susceptibility to prooxidant plant allelochemicals, quercetin (a flavonoid), and xanthotoxin (a photoactive furanocoumarin). Induction of SOD activity which rapidly destroys superoxide radicals, appears to be the main response to dietary prooxidant exposure. A unique observation includes high constitutive activity of CAT and a broader subcellular distribution in all three insects than observed in most mammalian species. These attributes of CAT appear to be important in the prevention of excessive accumulation of cytotoxic H2O2. Unlike mammalian species, insects possess very low levels of a GPOX-like activity toward H2O2. Irrefutable proof that this activity is due to a selenium-dependent GPOX found in mammals, is lacking at this time. However, the activity of selenium independent GTpx is unusually high in insects, suggesting that GTpx and not GPOX plays a prominent role in scavenging deleterious LOOHs. The GSSG generated from the GPOX and GTpx reactions may be reduced to GSH by GR activity. A key role of SOD in protecting insects from prooxidant toxicity was evident when its inhibition resulted in enhanced toxicity towards prooxidants. The role of antioxidant compounds in protecting these insects from toxic forms of oxygen has not been explored in depth. A major finding, however, is that these insects are lutein accumulators. Lutein is a dihydroxy (diol) derivative of beta-carotene, and it is a good quencher of activated forms of oxygen and free radicals. Levels of lutein are highest in P. polyxenes which specializes in feeding on prooxidant containing plants. PMID- 2199344 TI - Free radical generation by redox cycling of estrogens. AB - Natural and synthetic estrogens elicit normal hormonal responses in concentrations in a clearly defined yet low range. At elevated doses, metabolic reactions of the phenolic moiety, while harmless at low levels, may become the predominant biochemical activity and may exert deleterious effects. These metabolic pathways, such as i) oxidation of estrogens to catechol estrogens and further to their respective quinones, and ii) free radical generation by redox cycling between catechol estrogens or diethylstilbestrol and their quinones, are investigated for their influence in physiological or pathophysiological processes. In this review, the in vitro capacity of various enzymes to oxidize estrogen hydroquinones to quinones or to reduce corresponding quinones to hydroquinones is evaluated. The in vivo activities of enzymes supporting redox cycling of estrogens and free radical generation is correlated with induction of kidney tumors in Syrian hamsters. Concomitant changes in activities in quinone reductase and other detoxifying enzymes in kidneys of hamsters treated with estrogen support a role of free radicals in the induction of tumors by estrogen. Free radical damage to protein and possibly to DNA in kidneys of estrogen-treated hamsters may be used as markers of free radical action in vivo. PMID- 2199345 TI - Pathogenesis of chronic pancreatitis. PMID- 2199346 TI - Relation between T cell number and epithelial HLA class II expression quantified by image analysis in normal and inflamed human gastric mucosa. AB - Epithelial expression of HLA class II determinants and the number of lamina propria and intraepithelial T cells were quantified in gastric body mucosa by means of paired immunofluorescence staining which was subjected to computerised image analysis. In normal mucosa, epithelial HLA-DR expression was virtually absent. A significantly increased expression was seen in simple chronic gastritis, most extensively in the isthmus zone, where a positive reaction was seen in 34% of the epithelial area when the gastritis was of low degree and in 85% when it was of moderate severity. The most extensive HLA-DR expression was found in moderate 'stump gastritis' 28 to 32 years after Billroth II resections. In these patients the epithelial area in the foveolar and isthmus zones showed 83% and 92% positive responses, respectively. The HLA subregion products were expressed in a differential manner (DR greater than DP greater than DQ). The number of both intraepithelial and lamina propria T cells increased significantly with increasing severity of gastritis, and the fraction of putative memory T cells was also raised. Correlation analyses showed a positive relation between the epithelial expression of HLA-DR and the intraepithelial as well as the lamina propria density of T cell. These results suggest a biological link between T cells, aberrant HLA-DR expression, and gastritis, although the pathogenic importance of this relation is unknown. Enhanced epithelial presentation of autoantigens or luminal antigens, or both leading to increased activation of T cells is one possible explanation. PMID- 2199347 TI - Double blind comparative study of omeprazole and ranitidine in patients with duodenal or gastric ulcer: a multicentre trial. Cooperative study group. AB - We studied omeprazole and ranitidine in promoting duodenal ulcer healing in a multicentre trial by comparing the proportion of healed ulcers after two, four, and eight weeks of treatment. Altogether, 194 patients (143 men) were randomly allocated according to a prearranged treatment schedule to either drug and were treated double blind. Each received 40 mg omeprazole in the morning and a ranitidine placebo morning and evening or 150 mg ranitidine morning and evening with an omeprazole placebo in the morning. A total of 188 patients (94 taking omeprazole, 94 taking ranitidine) completed the trial. Sixty four (68%) omeprazole treated and 45 (48%) ranitidine treated patients had healed ulcers at two weeks, 91 (99%) omeprazole treated and 79 (88%) ranitidine treated had healed ulcers by four weeks, and 91 (100%) omeprazole treated and 86 (97%) ranitidine treated patients had healed ulcers by eight weeks. The overall difference in healing rates was significant (p = 0.0008, Mantel-Haenszel test). The differences were significant also at two weeks (20%, 95% confidence interval 5.6 to 34.4, p less than 0.01) and at four weeks (11%, 95% CI 3.7 to 17.3, p less than 0.01), but not at eight weeks (3%, 95% CI -0.5 to + 7.3, p = 0.25), using the chi 2 statistic, the study having a power to detect a 20% difference on 90% of occasions. After two weeks of treatment complete symptom relief was observed in 70 (74%) patients receiving omeprazole and in 58 (62%) receiving ranitidine. Diary cards showed a significantly lower percentage of days with pain in the omeprazole treated group (7.4% v 21.4%, p < 0.02) when assessed over either the first two weeks or over weeks three and four treatment. A total of 144 patients with healed duodenal ulcer were followed up, with no treatment, for six months. At the end of this period 19 (26%) of 74 patients healed with omeprazole and 17 (24%) of 70 patients healed with ranitidine were still in remission. A similar protocol was used for 46 patients (25 men) with gastric ulcer who were randomly allocated to treatment with omeprazole or ranitidine as described above. Forty patients (16 omeprazole, 24 ranitidine) completed trial. Thirteen (81%) omeprazole treated and 14 (58%) ranitidine treated patients had healed ulcers at four weeks; at eight weeks 14 (93%) omeprazole treated and 20 (87%) ranitidine treated patients had healed ulcers. These differences were not significant at four weeks (p = 0.25) or eight weeks (p = 0.96). Twenty seven gastric ulcer patients were followed up for six months and seven (58%) of the 12 omeprazole healed and five (33%) of the 15 ranitidine healed patients were in remission at six months. Unwanted adverse events were trivial except for one fatality in a 67 year old women, who died from bronchopneumonia and myocardial ischaemia while receiving treatment with omeprazole, which was judged to be unrelated to her death. PMID- 2199348 TI - Bile duct antibodies crossreacting with blood group antigens in primary sclerosing cholangitis. AB - Indirect immunoperoxidase histochemistry was used to localise and determine the disease, species, and tissue specificity of bile duct antibodies in primary sclerosing cholangitis. Serum was collected from: 29 patients with primary sclerosing cholangitis, 18 patients with ulcerative colitis alone, 19 patients with extrahepatic biliary obstruction of other causes, and 42 healthy control subjects. Bile duct antibodies reacted with an antigen localised to the small and large intrahepatic bile ducts. When blood group A human liver was used they were detected in 34% of patients with primary sclerosing cholangitis. They were not detected when blood group O human liver was used. Bile duct antibodies that reacted with obstructed and normal rabbit liver were detected in 34% and 17% respectively of patients with primary sclerosing cholangitis but were also present in similar proportions of control subjects. Colon antibodies that reacted with human and rabbit colon were found in 52% and 24% respectively of patients with primary sclerosing cholangitis. Absorption studies using blood group substances A and B abolished the reactivity of bile duct antibodies with human and rabbit liver and that of colon antibodies' with rabbit colon. Colon antibodies that reacted with human colon were not absorbed. Absorption studies using isolated peripheral white blood cells did not affect reactivity of bile duct or colon antibodies. We conclude that bile duct antibodies are disease, species, and tissue non-specific and react with blood group A/B antigens present in human and rabbit bile ducts and rabbit colon. This suggests that they do not play a role in the pathogenesis of primary sclerosing cholangitis. PMID- 2199349 TI - Successful use of vancomycin hydrochloride in the treatment of lactulose resistant chronic hepatic encephalopathy. AB - Vancomycin hydrochloride (2 g daily) was administered to 12 patients with cirrhosis and lactulose resistant portal systemic encephalopathy in a double blind crossover trial. All 12 patients showed a remarkable clinical improvement after vancomycin treatment. The mean (SE) electroencephalographic (EEG) frequency changed from 6.3 (0.2) to 8.5 (0.2) cps (p less than 0.001) and the mean arterial ammonia concentration from 152 (4) micrograms/ml to 97 (8) micrograms/ml (p less than 0.001). Their clinical condition deteriorated when treatment was switched to lactulose, returning to the previous slower EEG frequency and high arterial ammonia concentrations. Vancomycin seems to be effective in chronic portal systemic encephalopathy in patients who are not helped by lactulose alone. PMID- 2199350 TI - Review of methods for measuring gliadins in food. PMID- 2199351 TI - Selection of a hyperproducing strain of Aspergillus niger for biosynthesis of citric acid on unusual carbon substrates. AB - Several tens of mutants were obtained by UV irradiation of a spore suspension of Aspergillus niger. Producers yielding large amounts of citric acid were selected on a modified Czapek agar containing methyl red as pH indicator. After a submerged cultivation in flasks with baffles, a mutant characterized by yellow pigmentation on wort agar and by yields of citric acid up to 74.6% in the medium containing glucose was chosen from 130 isolates tested. PMID- 2199352 TI - Dominant resistance to oxythiamin in Saccharomyces cerevisiae and its mapping. AB - A dominant mutation, responsible for the resistance to oxythiamin in Saccharomyces cerevisiae was mapped on the right arm of chromosome IV, 4.6 cM centromere-distally to trp1. The corresponding gene is not involved in the control of intracellular content of total thiamin during growth on a minimal medium without thiamin. PMID- 2199353 TI - Survey of the QSAR and in vitro approaches for developing non-animal methods to supersede the in vivo LD50 test. AB - Quantitative structure-activity relationship (QSAR) studies and in vitro studies in which correlations with LD50 have been sought are reviewed. QSAR methods have shown some success in relating LD50 to certain physicochemical properties of the compound, particularly lipophilicity, but have been less successful in correlating LD50 with electronic properties of molecules (related to reactivity) or structural variables. It is concluded that insufficient evidence is available to determine whether QSAR methods can be of general use in predicting the acute toxicity (LD50) of chemicals, and that until further work is undertaken to develop QSARs for a much wider range of homologous series of compounds, this situation is unlikely to be resolved. New chemical descriptors that are more directly relevant to the mechanism of toxic action of the chemical should be identified. Cytotoxicity in vitro is poorly correlated with LD50, but good correlations have been obtained between toxicity in vivo and in vitro, using systems in which the toxic endpoint reflects the probable mechanism(s) of acute toxicity of the test chemical (e.g. the assessment of neurotoxins using neural cell systems). Therefore, it seems that the successful application of in vitro methods requires a better understanding of the mechanisms of acute toxicity in vivo and the development of mammalian cell culture systems that can model more closely the metabolic fate of the chemicals in vivo. PMID- 2199354 TI - [Hormonal changes in the elderly from the viewpoint of the andrologist]. AB - Although the aging male experiences a decrease in genital function, it is not as pronounced or as complete as in the female ovary, so that this process is only remotely similar to the climacteric. The most important sign is a decrease in erection frequency and other sexual functions. This is, however, not due simply to a decrease in testosterone levels. For numerous studies have clearly shown that the number of sexual performances is independent of current testosterone levels. A qualitative change in Leydig cell function can, however, be concluded from the "latent androgen deficit", reduced stimulability of the Leydig cells, and the frequent anomalies of the levels of such other hormones as FSH and LH in patients with impotence. Thus, the treatment of "impotence" with oral or depot testosterone is indicated in proven manifest or latent androgen deficiency. PMID- 2199355 TI - [Diagnosis and therapy of erectile disorders]. AB - The current diagnostic and therapeutic possibilities in patients with erectile dysfunction are discussed. The anatomical and physiological aspects of erection, and the most frequent causes of erectile dysfunction are presented, with special consideration being given to the situation in the older man. PMID- 2199356 TI - [Sex disorders following urologic surgery]. PMID- 2199357 TI - [Sex disorders in male diabetic patients]. AB - Sexual disorders occur in about 50% of male diabetics, appearing in two different forms: (1) temporary disorders caused mainly be general disturbances due to metabolic derangements; (2) chronic disorders characteristic of diabetes, although their symptomatology is not typical. Here, erectile dysfunction predominates. The etiology has not yet been definitely clarified. Psychological, neurogenic, vascular and endocrine factors are all involved. In the individual case, it is necessary to identify the major causes by employing subtile investigative measures, in order to be able to plan rational treatment. PMID- 2199358 TI - [Drug therapy of disorders of cerebral performance. Randomized comparative study of dihydroergotoxine and Ginkgo biloba extract]. AB - In a randomized trial lasting six weeks and involving 80 elderly patients with cerebrovascular disorders, the effectiveness and tolerance of dihydroergotoxine was compared with an extract of Ginkgo biloba. On the basis of psychometric tests and assessment scales, it was shown that treatment with either substance improved the condition of the patients. While, for the most part, intergroup comparison revealed no major statistically significant differences, such changes, affecting various parameters, were found during follow-up--more frequently within the dihydroergotoxine group than within the group treated with Ginkgo biloba extract. PMID- 2199359 TI - [Cefuroxime axetil. An antibiotic advances]. PMID- 2199360 TI - [Giant axonal neuropathy--comparing with acrylamide poisoning]. PMID- 2199361 TI - [Experimental studies of the significance of pancreatico-enterostomy on the chronic pancreatitis]. AB - Little is known about endocrine function of the pancreas after it was treated with pancreatico-enterostomy for its chronic inflammation. In order to study this, an experimental model of chronic pancreatitis was made by ligating the canine main pancreatic duct, which was reconstructed eight weeks later by performing pancreatico-duodenostomy in the study group. Pancreatic endocrine function was studied before ligating the main pancreatic duct, 4, 8, 12, and 16 weeks after the ligation in the control group, or 4 and 8 weeks after the reconstruction in the study group. Histological changes of the whole pancreas were also examined when animal was sacrificed. The results of our study are as follows. 1) The endocrine function, which was studied by using IVGTT and calculating K-values, showed significant deterioration eight weeks after the main pancreatic duct ligation. 2) The endocrine function was significantly recovered eight weeks after the reconstruction. 3) Histological evidence of chronic pancreatitis was demonstrated 8 weeks after the main pancreatic duct ligation which was progressed to acinus loss and fibrosis after 16 weeks. The islets of Langerhans were shown to be structurally preserved 8 weeks after the ligation, but ultrastructural alternations 16 weeks after the ligation included apparent degeneration of islet cells. 4) Compared with the control group, fibrotic change of the pancreas was restrained and most of islets did not show degeneration 8 weeks after the reconstruction in the study group. 5) These results suggest that early surgical intervention is to be warranted for chronic pancreatitis, in order to preserve and recover the endocrine function. PMID- 2199362 TI - Sequelae to acromegaly: reversibility with treatment of the primary disease. AB - Acromegalic patients suffer from a number of cardiovascular, metabolic, and rheumatologic problems, and they may also have an increased incidence of malignancy. We reviewed the literature concerning the reversibility of acromegalic complications. Hypertension, myocardial hypertrophy, left ventricular dysfunction and some rheumatologic abnormalities often continue despite successful treatment of the acromegaly. In contrast, glucose intolerance, soft tissue changes, and carpal tunnel syndrome usually resolve when the acromegaly is cured. Studies of the incidence and mortality of cancer in acromegaly are conflicting, but several suggest an increased incidence of colorectal cancer. PMID- 2199363 TI - Increase in glucose-stimulated insulin release and insulin biosynthesis in isolated pancreatic islets from D-galactosamine-treated rats. AB - Insulin secretion in response to glucose, glucose-stimulated insulin biosynthesis and insulin content was studied in pancreatic islets freshly isolated from male Wistar rats (150-200 g) with galactosamine-induced hepatitis. Animals were sacrificed by decapitation 3, 6, 12 and 24 hours after a single intraperitoneal injection of 500 mg/kg of galactosamine. Isolated islets prepared by collagenase method were perifused in Swim's medium with 20 mM glucose at 37 degrees C up to 30 minutes. Samples were taken at 2-10 min intervals for insulin assay. Insulin biosynthesis was assessed by the incorporation of [3H]-leucine into immunoprecipitable products (insulin and proinsulin) in pancreatic islets after 120 min incubation with 20 mM glucose. Glucose-stimulated insulin secretion was significantly increased at 6, 12 and 24 hours following the administration of galactosamine compared to control. The rate of insulin biosynthesis was stimulated to 170, 138 and 185% of control level 3, 6 and 12 hours after galactosamine-treatment, respectively. Significant increase in insulin content of islets was found 24 hours after galactosamine treatment, following the increased insulin biosynthesis. The present results indicate that pancreatic B cell function is activated in early stage of acute liver injury. PMID- 2199364 TI - Standard breakfast test: an alternative to glucagon testing for C-peptide reserve? AB - We measured C-peptide after glucagon and breakfast tests to compare the effectiveness of both tests in evaluating residual beta cell function in normal and diabetic subjects. A significantly higher C-peptide response was elicited after standard breakfast in patients with insulin-dependent diabetes mellitus of less than two years' evolution, ranging from 0.12 +/- 0.07 to 0.83 +/- 0.18 ng/ml (P less than 0.05). In nonobese noninsulin-dependent diabetes mellitus the response ranged from 0.86 +/- 0.02 to 1.89 +/- 0.48 ng/ml (P less than 0.0025); in obese NIDDM from 1.02 +/- 0.37 to 1.55 +/- 0.46 ng/ml (P less than 0.05), and in normal subjects from 0.77 +/- 0.23 to 2.11 +/- 1.22 ng/ml (P less than 0.0025). We conclude that the standard breakfast test is a useful and practical approach to the study of residual beta cell function. PMID- 2199365 TI - Urinary excretion of digoxin-like factor (DLF) and ADH during DOCA-salt and Goldblatt 2 kidney-1 clip hypertension development. AB - Urinary digoxin-like factor, ADH, sodium and potassium excretion and urine osmolality were studied during the development of two pathogenically different models of hypertension, DOCA-salt (low-renin) and Gold-blatt 2 kidney-1 clip (renin-dependent). Urinary digoxin-like factor was increased in rats that were given saline (NaCl 1%) to drink, uninephrectomized-salt and DOCA-salt rats, with no significant differences between the two groups urinary ADH was elevated in DOCA-salt rats during the study, compared with uninephrectomized-salt rats. Urinary digoxin-like factor and urinary ADH were not significantly modified in Goldblatt 2 kidney-1 clip and sham-operated rats. In addition, positive correlations between digoxin-like factor urinary excretion and urinary ADH and also with sodium urinary excretion were found. These data suggest that: a) digoxin-like factor and ADH could play a role in the pathogenesis of DOCA-salt but not in Goldblatt 2 kidney-1 clip hypertension. b) A common mechanism may stimulate ADH and digoxin-like factor simultaneously. c) Digoxin-like factor plays a role in the control of urinary sodium excretion. PMID- 2199366 TI - Inhibition of insulin secretion by rat mesenteric lymphocytes in incubated pancreatic islet cells. PMID- 2199367 TI - Genetic studies of human apolipoproteins. XV. An overview of IEF immunoblotting methods to screen apolipoprotein polymorphisms. AB - Genetically determined structural variation in the gene products of various apolipoproteins plays a significant role in modulating lipid levels in the population at large. However, due to tedious and cumbersome experimental problems involved, the detailed characterization of this genetic variation has been limited. The recent development of simple and sensitive isoelectric focusing and immunoblotting methods has circumvented these technically associated problems to a large extent, and this has allowed us to expand the genetic data on various apolipoproteins to previously uncharacterized populations. We have reviewed here these isoelectric focusing and immunoblotting methods. A comprehensive listing of allele frequencies has also been given for the polymorphic apolipoproteins. PMID- 2199368 TI - [Functions and relevance of the terminal complement sequence]. AB - The terminal complement sequence is initiated upon cleavage of C5 with liberation of C5a anaphylatoxin, and involves the assembly of macromolecular C5b-9 complexes either on cell surfaces or in plasma. Cell-bound C5b-9 complexes generate transmembrane pores that can cause cell death, or they can elicit secondary cellular reactions triggered, for example, by passive flux of calcium ions into the cells. In vivo functions of the fluid-phase SC5b-9 complex have not yet been defined, but the identity of S-protein with vitronectin (serum spreading factor) provokes the anticipation that significant biological functions of this complex do exist. The terminal complement sequence may fulfill protective functions when it is triggered on alien cells that are marked for destruction. Dysregulation in the complement sequence may, however, result in detrimental attack by C5b-9 on autologous cells. Examples include not only autoimmune disease states, but also the activation of complement on dead or dying cells, and bystander attack on blood cells during cardiopulmonary bypass. Methods for detecting and quantifying C5b-9 are outlined, and the potential usefulness of such assays in clinical research is discussed. PMID- 2199369 TI - Increased activity of FIM in serum of mice during a Mycobacterium bovis (BCG) infection. AB - In mice given an intravenous injection of Mycobacterium bovis (BCG), the bacilli proliferated in the spleen, liver and lungs but the peritoneal cavity remained sterile. The numbers of blood monocytes and alveolar macrophages were increased during the first 2 weeks of the infection, whereas the number of peritoneal macrophages remained constant. To study whether factor-increasing monocytopoiesis (FIM) plays a role in the regulation of the monocytosis during the BCG infection, the activity of this factor in the serum of mice at various intervals during the infection was determined. Previous studies have shown that FIM stimulates monocyte production by its effect on the mitotic activity of monoblasts and promonocytes in the bone marrow. The FIM activity of the serum reached a maximum on Day 4 and remained elevated during the first 21 days of the BCG infection. Since FIM is synthesized and secreted by macrophages that have phagocytosed opsonized particles, it is highly probable that FIM occurring in serum originates from macrophages that have ingested BCG. The results of the present study led to the conclusion that FIM plays a role in the monocytosis developing during infection with BCG. PMID- 2199370 TI - Distribution of lymphocyte subsets in the large intestinal lymphoid follicles of lambs. AB - The phenotypes of lymphocytes in the large intestinal patches (LIP) of lambs were examined by flow cytometry and immunohistology, using a panel of monoclonal antibodies (mAb), and compared to those found in the jejunal (JPP) and ileal Peyer's patches (IPP). T-cell markers were detected on 25% of the LIP and JPP lymphocytes by cytofluorometry, and nearly all T cells expressed the CD4 molecule. In contrast, T cells were scarce in the IPP (less than 1%). The B-cell marker p220 was expressed by 74% of the LIP lymphocytes, whereas surface immunoglobulin-positive cells comprised 50-60% of the lymphocyte population. The adhesion molecule CD2 was expressed by a larger proportion of cells from the LIP and JPP than from the IPP, whereas the adhesion molecule CD44 was detected on more IPP lymphocytes. Major histocompatibility complex (MHC) class I antigens were expressed by nearly all lymphocytes from the LIP, JPP and IPP. The LIP contained 70-80% cells with MHC class II expression, whereas the majority of IPP cells (greater than 95%) were MHC class II positive. Immunohistology showed many CD4+ T lymphocytes in the follicles of the LIP and JPP, but none in the IPP follicles. CD8+ lymphocytes were found in the interfollicular areas and were absent from the follicles. The interfollicular areas of the rectal patch contained about 15% tau delta T cells. In contrast, the JPP, IPP and the colon patch at the beginning of spiral colon contained less than 3% tau delta T cells. PMID- 2199371 TI - The experimental observation that led to discovery of angiotensin. 1939 Buenos Aires, Argentina. PMID- 2199372 TI - Hypertension research. A memoir 1920-1960. PMID- 2199374 TI - Occupational ethylene oxide exposure and reproduction. AB - Animal and epidemiological studies on the reproductive toxic effects of ethylene oxide (ETO) were considered in relation to occupational exposure levels (OELs) of ETO in the occupational environment of sterilisation units. Actual exposure levels in sterilisation units at Belgian and Dutch hospitals are presented and compared to data from recent studies conducted elsewhere. The animal studies did not match the actual exposure situation, involving a pattern of high peak levels and low time-weighted average levels. This may be the reason why epidemiological studies show contrasting results; they suggest reproductive toxicity of ETO at actual exposure levels. However, human data are scarce. There is a need for animal studies with a design that reflects the actual exposure situation. Epidemiological studies on reproductive events are also needed and a multi country study would seem to be a possible approach, provided that the study design and data collection method are standardised. PMID- 2199373 TI - Embryotoxic/teratogenic potential of halothane. AB - The embryotoxic/teratogenic potential of halothane was evaluated on the basis of available data obtained in an extensive literature search. It was found that halothane induced ultrastructural visible changes in the offspring of rats exposed to concentrations of 10 ppm during gestation. These consisted of degenerative changes in the cerebral cortex and, in particular, the weakening of cell membranes and the vacuolisation of the Golgi-complex. Macroscopically visible morphological changes were seen in rats only after exposure to concentrations equivalent to 320-fold (1600 ppm) the MAK value (maximum concentration value at the workplace). Furthermore, behavioural disorders were seen when exposure to concentrations greater than or equal to 10 ppm occurred during gestation and after parturition. In mice, only macroscopical investigations were performed. The first disturbances scored were only visible as retardation in the offspring, and occurred after exposure to concentrations of halothane 200-fold (1000 ppm) the MAK-value. In the rabbit, anaesthetic concentrations of 22000 ppm halothane did not result in an embryotoxic/teratogenic effect. The individual epidemiological findings in humans were discussed controversially. The studies are inconclusive in establishing an embryotoxic/teratogenic risk following sole exposure to halothane at the MAK level, since mixed exposures occurred and data on the concentrations of halothane in the inhaled air were missing. Therefore, the decision on whether halothane can impair intrauterine development is primarily based on the animal experimental findings. As long as a threshold value has not been established for the observed lesions, halothane should not be inhaled during pregnancy. PMID- 2199376 TI - Bioartificial pancreas: status and bottlenecks. PMID- 2199375 TI - The quest for interaction: studies on combined exposure. AB - A literature review was performed on the subject of combined exposure to stressors in the working situation. A general, dynamic model of workload served as the theoretical framework for the study. In this model, every factor that triggers a physiological or psychological response in the worker is regarded as a stressor. Decision latitude plays an important role in the model. A quantitative and qualitative analysis was performed on the available literature. It was concluded that the stressors that appear in studies on combined exposure stem mostly from the physical, chemical and biological environment. The task contents, the labor conditions, social relationships at work and the decision latitude are considerably less often studied in relation to combined exposure. It is concluded that important concepts in the study of combined exposure (e.g. interaction, independence, synergism, antagonism) are often quite carelessly mentioned in the literature. Explicit definition of these concepts is lacking in many publications. Establishment of maximum exposure levels is not yet possible for most stressor combinations. Examples are given of combinations that do allow more or less definite conclusions. It is recommended that more studies should be interdisciplinary organized. More studies are necessary in the field, studying effects of long exposure periods in the working population instead of studying students in laboratory situations. Exposure of susceptible groups, such as older workers and partially disabled workers, deserves special attention. PMID- 2199377 TI - The invention of the artificial kidney. PMID- 2199378 TI - Recombinant human erythropoietin and peritoneal dialysis. PMID- 2199380 TI - Alternatives to natural science foundations for nursing. AB - The underlying philosophical assumptions associated with the current vogue for humanistic and holistic approaches to nursing have not been subjected to systematic scrutiny, laying nursing open to the charge of being anti-scientific and even irrational. This paper outlines some of these assumptions and their origins, and proceeds to a brief survey of their impact on nursing theory, education and practice. It concludes with a call for the elucidation and consolidation of nursing practice which reflects phenomenological and humanistic alternatives to the natural science principles which have characterized traditional medical practice. In this connection I have used the term 'positivism' to refer to a general orientation according to which the world can only be known through observable entities, and regularities may be demonstrated and general laws verified through their measurement and quantification. PMID- 2199379 TI - Influence of membranes on generation of beta 2 M and release of leukocyte lysosomal enzymes. AB - Normal leukocyte functional capacity was investigated by evaluation of phagocytosis of opsonised yeast cells in a radiometric test system. After incubation with dialysis membranes (different cellulosic membranes, polysulfon membrane (PS), polymethylmetacrylate membrane (PMMN), the phagocytosis index, expressed as percent decrease with respect to initial values without membrane, decreased by 10%-25%. The most pronounced effect was observed with PS, cuprophane, modified cellulose and PMMA. The results are not related to differences in the viability of PMN during the test procedure; dead PMN amounted to about 4-6.5%. A significant increase in beta-NAG and beta-Gluc activities was released in the supernatants of the phagocytosis suspensions. This increase activity can be explained by the phagocytosis of PMN but it was not influenced by membrane contact. There was no influence of membrane contact or phagocytosis activity of PMN on the beta 2 M concentration in the supernatant demonstrating that no in vitro generation during incubation with either membrane exists. PMID- 2199381 TI - Expressed emotion and psychosocial intervention: a review. AB - For thirty years research has been consistently demonstrating the validity of the concept of 'High Expressed Emotion' (HEE). After early pioneering work by Brown it was established that environmental influences, particularly, the emotion expressed by relatives to sufferers of schizophrenia, are strongly implicated in relapse. Consequently, the predictive validity of HEE has been revealed in a number of cross-cultural studies around the world. In addition, there is strong evidence from well designed intervention studies, that relapse, in schizophrenic clients living at home, can be prevented by the manipulation of social and environmental factors. The combined body of research that has now accumulated allows an hypothesis to be made about the aetiology of the illness, schizophrenia, itself. This theory has been described as the 'stress vulnerability' model. The paper concludes that psychosocial intervention strategies are effective but that, unfortunately, to date, their application has been mostly restricted to the intervention studies themselves. PMID- 2199382 TI - The application of the concept of expressed emotion to the role of the community psychiatric nurse: a research study. AB - The previous article examined the development of the concept of 'expressed emotion', argued that controlled studies had successfully demonstrated the value of psychosocial intervention, but demonstrated that such a therapeutic approach had been mostly limited to the research studies themselves. In the light of the demonstrable efficacy of psychosocial intervention, the psychiatric nursing literature is reviewed in order to establish how far nurses have capitalized on the utility of the 'expressed emotion' concept, to date, in their work with schizophrenic clients and their families. In addition, a brief historical overview of the Community Psychiatric Nurses' (CPNs) role with schizophrenic clients is presented which relates to current ongoing research in this area which is described. In brief, the research project, which is funded by the Department of Health, is evaluating the outcome of teaching CPNs to deliver psychosocial interventions to families caring for a schizophrenic relative at home. PMID- 2199383 TI - Initiating breastfeeding: a world survey of the timing of postpartum breastfeeding. AB - A survey of the 'Human Relations Area Files' and ethnographic infant feeding literature from all cultures on the timing of infant feeding revealed that the practice of withholding colostrum from the infant was widespread. Data obtained from 120 cultures showed that in 50 cultures this delay in implementing breastfeeding was more than two days. In many groups, substitute prelacteal feeds were given, while in others, practices such as the use of purgatives exacerbated the risk of dehydration in the infant. The authors warn that nurses and midwives must be aware of the practice of withholding colostrum from the infant, and note that if a mother does not wish to breastfeed in the immediate postpartum, this does not necessarily mean that she wishes to bottle feed the infant. PMID- 2199384 TI - Epidemiological features of glaucoma. PMID- 2199385 TI - Genetic influences in open-angle glaucoma. PMID- 2199386 TI - Glaucomatous visual loss: field, color, and contrast. PMID- 2199387 TI - Angle-closure glaucoma. PMID- 2199388 TI - Laser therapy in glaucoma: an overview and update. PMID- 2199389 TI - Drainage implant surgery for refractory glaucoma. PMID- 2199390 TI - Extracapsular cataract extraction, intraocular lens implantation, and trabeculectomy: the combined procedure. PMID- 2199391 TI - Glaucoma and myopia: are they related? PMID- 2199392 TI - Use of a new device in cannulation of the great vessels: cannula introducer. AB - To improve the existing complications of the arterial cannulation technique, an introducer was developed that could minimize the trauma to the vessel wall and intima, simplify the operation and avoid the usual complications such as air or emboli strokes, misdirection and malrotation of the cannula tip within the artery. The Introducer consists of an extendable blade proportionate to the size of the cannula to be inserted. The movement of the blade is accomplished by a trigger in the handle of the device. The cannula is also released by another trigger in the handle. Ninety heart patients in whom this device was used underwent open heart surgery, and there were no single case of a major stroke, air or thrombo-embolism, or undue blood loss. One patient developed a transient right hand paresis that subsided after removal of the arterial line. The results were compared to 65 patients with the current method of cannulation and in whom this device was not used. In this latter group there were five cases of major neurological deficits, one aortic dissection, one case of embolism to the leg and four cases of abnormal bleeding which necessitated takebacks in the first 24 hours of post-operative period. PMID- 2199393 TI - Ultrasonographically demonstrated nutcracker phenomenon: alternative to angiography. AB - We report on a child with nutcracker phenomenon, which is a possible cause of intermittent gross haematuria of unknown origin. Early serial ultrasound examinations can demonstrate the lesions. The merits and demerits of conventional angiographic imaging are also discussed. PMID- 2199394 TI - Efficacy of orchiectomy versus high dose polyoestradiol phosphate (160 mg) in relieving infravesical obstruction in patients with prostatic cancer. AB - Post voiding residual urine volume (78 patients) and maximum urinary flow rate (59 patients) were measured in prostatic cancer patients treated by orchiectomy or oestrogen (polyoestradiol phosphate 160 mg i.m. monthly) to compare the effects of these endocrine treatments on bladder outlet obstruction caused by prostatic carcinoma. The relieving effect of orchiectomy seemed to be more apparent than that of high dose oestrogen during the first six months of therapy. PMID- 2199395 TI - [Echocardiography. Function analysis from morphology and dynamics]. PMID- 2199396 TI - [Digital image processing in echocardiography]. PMID- 2199397 TI - [Computerized tomography versus nuclear magnetic resonance tomography in clinical diagnosis of cardiac diseases]. PMID- 2199398 TI - [Nuclear medicine methods in cardiologic diagnosis]. PMID- 2199399 TI - [Coronary angiography and ventriculography]. PMID- 2199400 TI - [Mapping methods for localizing the origin of tachycardic arrhythmia]. PMID- 2199401 TI - [Differential diagnosis of thoracic aortic aneurysm]. PMID- 2199402 TI - A phase II trial of carboplatin (NSC 241240) in advanced prostate cancer, refractory to hormonal therapy. An Eastern Cooperative Oncology Group pilot study. AB - Twenty-nine patients with metastatic prostate cancer progressing after hormonal therapy (orchiectomy 19, diethylstilbestrol 10) and who had never received cytotoxic therapy were treated with carboplatin. Patients had good clinical performance status (66% PS 0,1) and adequate renal (creatinine less than 2.0 mg/dL) and bone marrow function. The standard dose of carboplatin administered was 400 mg/sq m. Seventeen patients received this dose and 12 either 320 mg/sq m or 250 mg/sq m based on reduced renal function or prior radiation. Five patients had bidimensionally measurable disease: one experienced a partial regression of cervical lymph node metastases of 97 days duration. Twenty-four patients had metastatic disease evaluable by clinical status, bone scan and acid phosphatase. In one patient greater than 50% reduction in number of abnormal areas of bone scan uptake occurred; 3 patients experienced improvement in clinical status; in no patient did an elevated prostate acid phosphatase return to normal. All patients entered on study have progressed and died: median time to progression was 94 days (6 to 625 days); median survival was 297 days (6-1152 days). The primary toxicity of carboplatin was myelosuppression. The median WBC and platelet nadirs after cycle one were 3150/cu mm and 93,000/cu mm, respectively. Dose escalations to grade 2 or greater myelosuppression were mandated. Twenty-six achieved at least grade 2 myelosuppression during carboplatin treatment. We conclude that carboplatin administered at this dose and schedule has no important activity in hormone refractory prostate cancer. PMID- 2199403 TI - Moshe Prywes, editor-in chief of the Israel Journal of Medical Sciences--laureate of the Israel prize for medicine. The Israel Journal of Medical Sciences celebrates its 25th anniversary. PMID- 2199404 TI - Fetal blood flow velocity waveforms in pregnancies complicated by intrauterine growth retardation. AB - Fifty-three pregnancies suspected for a small-for-gestational age fetus (SGA) by ultrasonographic weight estimation (below the 10th percentile of Brenner nomograms) were studied using pulsed Doppler (Duplex) for recording fetal blood flow velocity waveforms from the umbilical artery and fetal internal carotid artery. The pulsatility index (PI) for each artery was calculated as an index of vascular resistance. The gestational age ranged from 29 to 40 weeks. In 42 cases an SGA newborn was delivered (according to Brenner tables corrected for maternal parity and fetal sex), 34 newborns were SGA according to Usher and McLean (2 SD below the mean). Fetal structural and/or chromosomal defects were found in four cases, all of which showed symmetric intrauterine growth retardation and normal PI values in the fetal internal carotid artery. After excluding the infants with congenital abnormalities and using nomograms constructed for our own population, the ratio between the PI of the umbilical artery and the internal carotid artery was found to be the best predictor of SGA (sensitivity 84.2%, specificity 90.9%, positive predictive value 97.0%, negative predictive value 62.5%). Using the more demanding criteria for SGA according to Usher and McLean, sensitivity improved to 100%, specificity was 80.0%, positive predictive value 87.9%, and negative predictive value 100%. PMID- 2199405 TI - Unusual presentations of aortoiliac aneurysms. AB - Unusual presentations of aortoiliac aneurysms may be the reason for a delay in diagnosis of potentially life-threatening conditions. Five such unusual clinical pictures are presented and discussed. The aneurysms were falsely diagnosed as malignant disease, renal colic, sciatic syndrome, intra-abdominal bleeding of unknown origin, and psoas muscle abscess. The medical staff was misled by the atypical complaints, signs and symptoms, which resulted in a dangerous delay in diagnosis. The use of currently available ultrasonography and CAT scans, which enables early diagnosis, depends on the alertness of clinicians when they confront an atypical clinical picture that may be the first clue of a noninnocent aneurysm of the aortoiliac complex. Early surgical intervention before dissection, rupture or fistulization occur ensures a positive outcome and avoids emergency procedures with their attendant high operative mortality and postoperative morbidity. PMID- 2199406 TI - Early prenatal ultrasonic diagnosis of thanatophoric dwarfism. PMID- 2199407 TI - Calcium-activated, phospholipid-dependent protein kinase (protein kinase C): general aspects and experimental considerations. AB - Calcium-activated, phospholipid-dependent protein kinase (protein kinase C) is a ubiquitous serine and threonine protein kinase that has been implicated in the regulation of a wide variety of cellular functions. Protein kinase C is tightly linked to signal transduction through phosphatidylinositol turnover, and interacts with the cAMP-protein kinase A pathway in either a "monodirectional" or "bidirectional" mode. The discovery and development of protein kinase C inhibitors and activators offer useful tools to investigate the role of the kinase in specific cellular functions. However, caution should be exercised in interpreting the results of these studies, with special attention directed at experimental design. The present review summarizes some of the general aspects of protein kinase C. Methodological considerations for planning experiments and interpretation of results are described. In addition, we present some examples for the role of protein kinase C in the pathogenesis of disease. PMID- 2199408 TI - Acute gastroenteritis due to double infection with enteropathogenic Escherichia coli or Salmonella and another bacterial pathogen. AB - Two enteric bacterial pathogens were concomitantly isolated from the feces of 18 infants less than 6 months of age admitted to the Assaf Harofeh Medical Center over a 7-year period. In all but two patients stool cultures grew enteropathogenic Escherichia coli, six of serogroup 0119. The other organisms cultured were Shigella, Salmonella, Campylobacter jejuni and Aeromonas hydrophila. The usual clinical presentation was diarrhea, dehydration and vomiting of acute onset, and low grade fever. Patients with gastroenteritis due to a single agent compared with multiple pathogens had a milder course of disease, a milder degree of dehydration and acidosis, a lesser need for i.v. fluid treatment and shorter hospitalization. PMID- 2199409 TI - Mast cells in nonallergic immune responses in vivo. PMID- 2199410 TI - A comparison between conservative treatment and operative treatment (capsulosyndesmorrhaphy) in severe acute capsuloligamentous lateral lesions of the ankle joint. AB - The authors report 31 cases of acute severe capsuloligamentous lateral lesions of the ankle joint, 12 of which were treated surgically and 18 with a below knee plaster cast. An evaluation of the results at an average 20 months follow-up showed the superiority of the conservative method. PMID- 2199411 TI - Models of hip prosthesis mobilisation. AB - The mechanisms of prosthetic hip mobilisation are analysed, both in regard to the acetabular component and the femoral component. These are correlated with the clinical and radiographic manifestations with the aim of facilitating the comprehension and memorisation of different types of mobilisation. These are summarised in a chart illustrating the eight different mechanisms which provide both the orthopaedist and the radiologist with a rapid "aide memoire" when faced with a radiograph in a case of aseptic prosthetic hip mobilisation. PMID- 2199412 TI - [Granuloma annulare following Pfeiffer glandular fever]. PMID- 2199413 TI - [Digital 20 MHz sonography of basalioma in the B-scan]. AB - Digital 20 MHz b-scan sonography is a new non-invasive tool in dermatological routine diagnostics. The 20-MHz linear scanner employed in this study has a signal penetration of 7 mm, a lateral resolution of 200 microns and an axial resolution of 80 microns. Seventy-five basal cell carcinomas were examined by ultrasound. An exact correlation of histological slides and sonographic images allowed us to explain the sonographic phenomena of basal cell carcinoma (BC). BCs exhibit a well-defined area with poor echoes; they sometimes even show a total loss of reflection. In the tumor parenchyma inhomogenously distributed internal echos were found. Below the tumor post-tumoral enhancement of the signal reflection is common (depending on the type of BC -up to 70%). Our results prove that digital 20 MHz ultrasonic imaging systems are well suited for studying the extension, thickness and tissue texture of basal cell carcinoma. PMID- 2199414 TI - Medicare home health utilization as a function of nursing home market factors. AB - Rapid increases in the size and costs of the home health market, unknown impacts of Medicare's DRG hospital reimbursement on the posthospital market, and general lack of knowledge about factors that explain interstate variation in home health utilization all suggest the importance of developing and testing models of Medicare home health use. This article proposes and tests a model of state home health utilization as a function of the nursing home market. This model proposes that home health utilization is a function of nursing home bed capacity, of the utilization of nursing home beds by Medicaid patients, of other demand factors, and of supply factors. This model is supported by the data. Specifically, Medicare home health use in the 1978-1984 period was found to be negatively related to nursing home bed stock, positively related to Medicaid nursing home utilization, and related to several other supply and demand factors, as hypothesized by the model. The further model assumption that home health utilization does not affect the nursing home market could not be tested in this analysis, but will be addressed in future research by the authors. PMID- 2199415 TI - [Perioperative preventive use of antibiotics in head and neck surgery]. AB - The results of five consecutive prospective trials define the role of perioperative antibiotic prophylaxis in head and neck surgery. For contaminated head and neck cases and for endonasal sinus surgery, a single-dose prophylaxis seems to be sufficient. Most clean cases do not need antibiotic prophylaxis. Risk factors for wound infection include nicotine or alcohol abuse, poor oral hygiene and increasing age. Previous radiotherapy seems to be of minor importance. PMID- 2199416 TI - [(Chemo-) prevention of second tumors in patients with head and neck neoplasms]. AB - This review discusses the possible role of chemoprevention in the improvement of survival rates and the prevention of secondary primary tumours in patients with head and neck cancer. Chemoprevention is a new treatment that is especially promising for high risk groups. The fear that the advantages of this treatment will be outweighed by the disadvantages of side-effects and toxicity has not been confirmed by current studies. Randomized studies are needed to show whether chemoprevention can reduce the frequency of second primary tumours. PMID- 2199417 TI - [Therapy of ear hematoma and ear seroma]. AB - Conservative techniques for the treatment of auricular haematomas are unsuccessful. We discuss different operative methods and compare our results with these techniques. In our opinion the method described by Kelleher is a simple and reliable method for the treatment of auricular haematoma and seroma. After incision and evacuation of the fluid, tie-over sutures over wet sponges achieve efficient obliteration of the subperichondrial space. The most important advantages of the technique are that no resection of cartilage is necessary, the obliteration of the subperichondral space is stable, the cosmetic results are good, and the complication rate is low. PMID- 2199419 TI - Estimation of complications for linear accelerator radiosurgery with the integrated logistic formula. AB - Radiosurgery techniques permit high doses of single fraction irradiation to be administered to small volumes of tumor with relative sparing of surrounding brain tissue. The tolerance of surrounding normal brain tissue to dose distributions from linear accelerator radiosurgery with different collimator sizes is an important factor that must be estimated by anyone using these treatment techniques. The exponential and linear quadratic versions of the integrated logistic formula were used to estimate the probability of brain necrosis at different doses for radiosurgical dose distributions administered by a 6 MV linear accelerator with a 5 arc technique for collimator sizes from 12.5 to 30 mm in diameter. Dose-volume isoeffect curves for a 3% risk of brain necrosis from linear accelerator radiosurgery were then calculated. These curves approximate those calculated for gamma knife radiosurgery and a published 1% dose-volume isoeffect line predicted for proton beam irradiation. Similar dose-volume isoeffect curves were calculated for single fraction radiosurgery boosts administered after 30 Gy of whole brain irradiation in 12 fractions. The integrated logistic formula appears to be a useful tool for estimating tolerance and providing guidelines for prescribing radiation doses for linear accelerator radiosurgery. PMID- 2199418 TI - Intraoperative radiotherapy during lung cancer surgery: technical description and early clinical results. AB - A phase I-II study of intraoperative radiotherapy (IORT) for Stage III lung cancer was performed in 34 patients during a period of 58 months. Loco-regional treatment included tumor resection if technically feasible, IORT boost of electron beams using moderate single doses (10-15 Gy) to tumor bearing areas and external photon beam irradiation (46-50 Gy in 5 weeks) using conventional fields. Indications for this study were unresectable hiliar tumors (14, 41%), and mediastinal, hiliar and/or chest wall residual disease following resection (20, 59%). Thirty-four procedures, with 40 IORT fields, have been analyzed to describe the relevant technical aspects and the toxicity. IORT was delivered using acrylic transparent cones of different diameters. Surgical approach consisted in a lateral thoracotomy in all patients (21 right side and 13 left side). Tissues included within the IORT field were: tumor or residual tumor tissues (34, 100%), collapsed lung parenchyma and main bronchus not surgically manipulated (14, 41%), bronchial stump and vascular suture following resection (19, 55%), mediastinal structures (20, 58%), and brachial plexus (1, 3%). The bronchial suture was covered with pleural or pericardial flap after IORT in 10 cases (29%). Life threatening toxicity related to IORT consisted in broncho-pleural fistula (1, 3%) and massive hemoptysis (1, 3%). Other reversible toxic events were acute pneumonitis (12, 85%) and esophagitis (10, 50%). Long term asymptomatic lung fibrosis was detected in 11 cases (32%). Median survival time for the entire group has been 12 months. With a median follow-up time of 12 months the freedom from thoracic recurrence rate is 30% (65% in cases with tumor resection). Projected actuarial survival rates at 4 years were 28% for resected group and 7% for unresected cases. This experience supports IORT as a feasible alternative modality to be used in the management of locally advanced lung cancer. Tolerance of thoracic organs to moderate doses of IORT appeared to be adequate and local control is achieved in certain patients. These results deserve further investigation and confirmation trials. PMID- 2199420 TI - Aladapcin, a new microbial metabolite that enhances host resistance against bacterial infection. Production, isolation, physico-chemical properties and biological activities. AB - We have constructed a new screening system for detecting microbial products that enhance host resistance against bacterial infection. It was found that a new compound with such activity is produced by a soil isolate classified as Nocardia sp. SANK 60484. The compound was isolated from the culture filtrate of the organism and named aladapcin after its amino acid composition. Aladapcin was obtained as an amphoteric white amorphous powder with the molecular formula, C13H25N5O5. It consists of 2 mol of D-alanine and 1 mol of meso-diaminopimelic acid. From the analysis of IR, 1H NMR and FAB-MS spectra, the structure was assigned to be a tripeptide. Aladapcin enhanced host resistance against an experimental Escherichia coli infection in mice at doses ranging between 1 and 100 micrograms/kg. PMID- 2199421 TI - Calcium-dependent anticandidal action of pradimicin A. AB - Pradimicin A shows candicidal activity at 10 micrograms/ml in vitro. The action of pradimicin A on Candida albicans cells involves a set of specific cell surface interactions in a Ca2(+)-dependent manner. These include binding to the mannan components on the cell surface and subsequent interactions at the level of the plasma membrane, causing K+ leakage and cell death. The protoplasts prepared from C. albicans undergo lysis rapidly when treated with pradimicin A. These results suggest that pradimicin A acts primarily on the candidal plasma membrane, leading to a perturbation of membrane function. PMID- 2199422 TI - Prof. Rezso Bognar. PMID- 2199423 TI - The neurology of organophosphorus insecticide poisoning newer findings a view point. PMID- 2199424 TI - Prophylactic use of mexiletine in the elderly with acute myocardial infarction. AB - A double blind randomised study comparing the effects of oral mexiletine and placebo given to elderly patients (65 years and older) immediately following hospital admission with suspected myocardial infarction (MI) is described. The study comprised one hundred and fifty-four patients of which 74 had confirmed myocardial infarction according to the diagnostic criteria of the study. Eighty patients without definite evidence of myocardial infarction were subsequently excluded from the study. Thirty-three patients (44.5%) with confirmed MI treated with mexiletine, compared with 41 (51%) in the placebo group showed no significant difference in mortality at 48 hours and 14 days. The mexiletine treated group showed a significant reduction (p less than 0.05) in certain forms of ventricular dysrhythmias. Six of these patients (18%) taking mexiletine had the drug withdrawn because of possible adverse drug reactions compared with two (4.8%) of the placebo group. None of the patients withdrawn because of possible adverse drug reactions had any long term side effect. Mild confusion observed in one patient was reversed after withdrawal of therapy. Results of this study indicate the safety of mexiletine as an anti-arrhythmic drug and its efficacy in suppression of certain ventricular dysrhythmias in the elderly with acute myocardial infarction. The overall mortality rate in both groups (mexiletine and placebo) remained unchanged. PMID- 2199425 TI - Campylobacter pylori. A new era in gastroduodenal disorders? PMID- 2199426 TI - Gemfibrozil in dyslipidaemia. AB - A new lipid regulating agent, Gemfibrozil was evaluated in different types of dyslipidaemias. Out of a total of 34 patients, all completed 12 weeks' treatment and 26 completed 24 weeks' of treatment. A significant reduction in total cholesterol, LDL-c triglyceride and apo-B and an increase in HDL cholesterol and its apoprotein--apo-A were observed. The patients belonged to hyperlipidaemias- types IIa, IIb, and IV. Patients' compliance was good and side effects were minimal. PMID- 2199427 TI - Diet, diabetes and atherosclerosis. PMID- 2199428 TI - Herniography in adults: review and personal studies. AB - In 120 adults (87 men, 33 women) with suspicion of a hernia but with normal physical examination, herniography disclosed 125 positive findings correlated with the clinical manifestations. There were no false positive or false negative herniographic diagnoses among 25 patients who underwent surgery. Herniography is a useful examination to evaluate patients with an uncertain or normal physical examination and with clinical manifestations suggestive for hernia. This relatively simple technique and the use of a non-ionic contrast medium are well tolerated. PMID- 2199429 TI - [Rapidly destructive coxarthrosis: case study and literature review]. AB - Rapidly destructive coxarthrosis is a rather rare disease that affects most frequently women between 60 and 66 years. This bone disease is defined by a rapid chondrolysis with total obliteration of the joint space in the superolateral segment of the joint in an average period of one year, followed by rapid bone destruction of the femoral head and the roof of the acetabulum. This periarticular osteolysis causes a rising of the femoral head. The radiographic appearance shows minimal osteophytosis but this is never absent. The study of follow-up radiographs is helpful to make a choice in the differential diagnosis among the ethiologies of a rapidly destructive hip. PMID- 2199430 TI - Winter depression responds to an open trial of tranylcypromine. AB - Seasonal affective disorder (SAD) is a disturbance of mood bearing a fixed relationship to season. Winter depression is characterized by the onset of a depressive syndrome in the fall or winter and spontaneous remission in the spring, this condition responds to full-spectrum, bright artificial light. In the first study assessing responsiveness of winter depression to a standard pharmacologic treatment for depression, the authors found that 14 patients meeting National Institute of Mental Health criteria for winter depression responded to treatment with tranylcypromine. PMID- 2199431 TI - The relationship between blood perphenazine levels, early resolution of psychotic symptoms, and side effects. AB - Serum perphenazine concentrations and early resolution of psychosis were examined to determine if blood level monitoring could be used to maximize drug efficacy while limiting extrapyramidal side effects (EPS). Sixty-six acutely psychotic inpatients were given perphenazine 0.5 mg/kg/day for 10 days, and their response was rated blind to blood level. Although 36 of 66 patients showed resolution of psychosis, neither perphenazine nor N-dealkylated perphenazine levels were related to global response or to Brief Psychiatric Rating Scale (BPRS) totals. Improvement in two individual BPRS items (hallucinations and conceptual disorganization) was related to serum perphenazine levels and suggestive of a lower therapeutic threshold of 0.8 ng/mL. Perphenazine level was not correlated with EPS; but benztropine, given only if required for serious EPS, was more likely to be used when perphenazine levels were elevated. The data suggest that higher perphenazine levels were no more effective than moderate levels but that higher levels may be associated with increased EPS; the data also suggest that individual symptoms rather than global response were associated with a lower therapeutic perphenazine threshold. PMID- 2199432 TI - Neurobiology of obsessive compulsive disorder: a possible role for serotonin. AB - At the current time, it appears that the only medications with consistent antiobsessional effects are the potent serotonin uptake blockers (clomipramine, fluoxetine, and fluvoxamine). Not only is serotonin uptake blockade an apparent prerequisite for clinical improvement, but there is a correlation between the magnitude of clinical response and the reduction in various serotonin markers during treatment with these drugs. Further evidence for the importance of serotonin in pharmacologic mediation of antiobsessional effects comes from a recent study in which administration of a serotonin antagonist (metergoline) to obsessive compulsive disorder (OCD) patients partly reversed the clinical improvement observed with clomipramine treatment. Although these observations have implicated serotonin in the mechanism of antiobsessional drug action, there is still little evidence demonstrating a role for serotonin in the pathophysiology of OCD. This review summarizes various studies of serotonin function in untreated OCD patients and concludes that the most compelling evidence for an abnormality has come from single-dose challenge studies of serotonin receptor agonists in untreated OCD patients. These studies remain controversial, but a preliminary interpretation of the results suggests that OCD patients may be more sensitive than healthy controls to the behavioral effects of one such serotonin agonist, m-CPP. An abnormality in the sensitivity to endogenous serotonin may link OCD research to the broader scientific question of serotonin's role in the modulation of aggression. PMID- 2199433 TI - Beyond the serotonin hypothesis: a role for dopamine in some forms of obsessive compulsive disorder? AB - It seems unlikely that a solitary disturbance in serotonin function can fully account for the pathophysiology of obsessive compulsive disorder. The authors propose that some forms of obsessive compulsive disorder, e.g., obsessive compulsive disorder with a history of Tourette's syndrome, may involve a relative or absolute derangement in both brain serotoninergic and dopaminergic systems. A role for dopamine in the pathophysiology of obsessive compulsive disorder is supported by a review of the preclinical and clinical evidence. Additional studies are needed to more directly evaluate dopamine function in patients with obsessive compulsive disorder. PMID- 2199434 TI - Lithium: the present and the future. AB - The potential benefits of lithium extend beyond the treatment of acute mania and maintenance of patients with bipolar disorder, the only indications currently approved by the U.S. Food and Drug Administration. When used as adjunctive therapy, lithium augments the therapeutic effects of conventional antidepressants and is particularly useful in patients with resistant depression. The efficacy of the drug in the treatment of alcoholism has been a matter of controversy for several years; the most recent data suggest that the agent has limited, if any, utility in this population. More promising applications have emerged in the management of obsessive compulsive disorder. Some evidence has also suggested that lithium may possess antiviral properties. Side effects, particularly those involving the thyroid and kidney, continue to generate concern, and drug-drug interactions must also be considered whenever lithium is prescribed. PMID- 2199435 TI - Worldwide use of clomipramine. AB - Clomipramine, a preferential inhibitor of 5-hydroxytryptamine uptake, has proven effective in the management of depression, resistant depression, and obsessive compulsive disorder. Investigators have also reported benefits of this medication in patients with phobia, panic disorder, chronic pain, Gilles de la Tourette's syndrome, premature ejaculation, anorexia nervosa, cataplexy, and enuresis. In double-blind studies of patients with depression, clomipramine has been significantly more effective than placebo and equivalent to standard tricyclics. Clomipramine is particularly well suited for the treatment of resistant depression, for which its efficacy may be enhanced by combination therapy with tryptophan and/or lithium. In at least 12 double-blind comparative trials, clomipramine has exhibited significant benefit in patients with obsessive compulsive disorder, this efficacy not being limited to patients with an associated depressive illness. In the United States, clomipramine is approved only for the treatment of obsessive compulsive disorder. PMID- 2199436 TI - Exercise induces recruitment of the "insulin-responsive glucose transporter". Evidence for distinct intracellular insulin- and exercise-recruitable transporter pools in skeletal muscle. AB - Acute exercise, like insulin, increases D-glucose uptake into rat hind limb muscles. Here we examine the distribution of the muscle glucose transporters GLUT 4 and GLUT-1 in plasma membrane and intracellular membrane fractions of skeletal muscle prepared from control, exercised, and acutely insulin-treated rats. Immunoblotting with an anti-GLUT-4 polyclonal antibody showed that acute insulin treatment (by hind limb perfusion or in vivo injection) increased GLUT-4 transporters in a plasma membrane fraction and decreased them in an intracellular membrane fraction. Exercise also increased the GLUT-4 transporters in the plasma membrane, but in contrast to insulin, did not significantly decrease them in the intracellular fraction. Immunoblotting with anti-GLUT-1 antibody revealed that this transporter is largely localized in the plasma membrane. Neither insulin nor exercise significantly increased GLUT-1 transporters in the plasma membrane. The data show that GLUT-4 is an insulin-responsive glucose transporter in skeletal muscle and, furthermore, that GLUT-4 also responds to acute exercise. The results are consistent with recruitment of GLUT-4 glucose transporters to the plasma membrane from intracellular stores. Moreover, exercise-sensitive GLUT-4 transporters do not originate from the insulin-sensitive intracellular membrane fraction, suggesting the existence of distinct intracellular insulin- and exercise-recruitable GLUT-4 transporter pools. PMID- 2199437 TI - Identification of catalytic residues in the beta-glucoside permease of Escherichia coli by site-specific mutagenesis and demonstration of interdomain cross-reactivity between the beta-glucoside and glucose systems. AB - beta-Glucoside Enzyme II (IIBgl) of the Escherichia coli phosphotransferase system transports and phosphorylates beta-glucosides, whereas the glucose Enzyme II-III pair (IIGlc-IIIGlc) transports and phosphorylates glucose as well as certain aliphatic alpha- and beta-glucosides. Comparisons of their respective amino acid sequences previously revealed that both systems are homologous and must be evolutionarily related. To gain more insight into the details of the transport mechanism, we made use of the observed homologies among phosphotransferase system permeases to design a suitable set of site-specific mutants within the gene encoding IIBgl. This set was used to study in vivo fermentation and to analyze in vitro P-enolpyruvate-dependent sugar phosphorylation as well as sugar phosphate-dependent sugar transphosphorylation. The following results were obtained. (i) IIBgl transports and phosphorylates glucose as well as aryl- and alkyl-beta-glucosides; (ii) histidyl 547 is essential for the phosphorylation of IIBgl by the histidine-containing phosphoryl carrier protein of the phosphotransferase system (HPr) (first phosphorylation site); (iii) both cysteyl 24 and histidyl 306 are essential for the transfer of the phosphoryl group to the sugar; (iv) replacement of Cys-24 by serine leads to uncoupling of sugar transport from phosphorylation; and (v) histidyl 183 is important for substrate specificity. Our studies also revealed heterologous phosphoryl transfer between the beta-glucoside and glucose permease components which probably occurs as follows: 1) HPr-P----IIBgl (His-547)----IIGlc----alkyl alpha- or -beta-glucosides or glucose (but not aryl-beta-glucosides) and 2) HPr-P ---IIIGlc----IIBgl (Cys-24 or His-306)----alkyl- or aryl-beta-glucosides or glucose (but not methyl-alpha-glucoside). In addition to the essential residues noted above, several residues in IIBgl were identified which when mutated reduced the in vitro catalytic efficiency of the enzyme more than 10-fold. Thus, aspartyl 551 and arginyl 625 appeared to function together with histidyl 547 in phosphoryl transfer involving the first phosphorylation site in the permease, whereas histidyl 183 appeared to function together with cysteyl 24 and histidyl 306 in phosphoryl transfer involving the second phosphorylation site in the permease. PMID- 2199438 TI - [32P]3'-O-(4-benzoyl)benzoyl ATP as a photoaffinity label for a phospholipase C coupled P2Y-purinergic receptor. AB - A 32P-labelled ATP analog, 3'-O-(4-benzoyl)benzoyl ATP (BzATP) previously shown to be an agonist at P2Y-purinergic receptors (Boyer J. L., and Harden T. K. (1989) Mol. Pharmacol. 36, 831-835), has been used as a probe for the P2Y purinergic receptor on turkey erythrocyte plasma membranes. In the absence of light, [32P]BzATP bound to membranes with high affinity (KD approximately 5 nM), and in a saturable and reversible manner. The binding of [32P]BzATP was competitively inhibited by ATP and ADP analogs (2-methylthioadenosine 5' triphosphate greater than adenosine 5'-O-(2-thiodiphosphate) greater than BzATP greater than ATP greater than beta,gamma-methyleneadenosine 5'-triphosphate greater than 5'-adenylylimidodiphosphate) with pharmacological specificity consistent with that of a P2Y-purinergic receptor. Guanine nucleotides (guanosine 5'-O-(3-thiotriphosphate) greater than GTP greater than guanosine 5'-O-(2 thiodiphosphate) greater than GMP) noncompetitively inhibited the binding of radioligand. Photolysis of [32P] BzATP-prelabeled membranes resulted in incorporation of radiolabel into a protein of approximately 53,000 Da. Photolabeling was inhibited in a concentration-dependent manner by ATP and ADP analogs with a potency order characteristic for a P2Y-purinergic receptor and was modulated by guanine nucleotides. A protein of approximately 53,000 daltons was also labeled by [32P]BzATP in membranes from several other tissues known to express the P2Y-purinergic receptor. These results suggest that [32P]BzATP can be used to label covalently the P2Y-purinergic receptor and that this radioprobe will be a useful reagent for further characterization and purification of the P2Y purinergic receptor. PMID- 2199439 TI - The hypoxanthine-guanine phosphoribosyltransferase of Schistosoma mansoni. Further characterization and gene expression in Escherichia coli. AB - Due to the lack of de novo purine nucleotide biosynthesis, hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) is an essential enzyme in the human parasite Schistosoma mansoni for supplying guanine nucleotides and has been proposed as a potential target for antiparasitic chemotherapy. While the enzyme can be purified from adult schistosome worms, yields are too low to allow extensive structural and kinetic studies. We therefore cloned and sequenced the cDNA and gene encoding the schistosomal enzyme but were unable to positively identify the amino-terminal sequence of the enzyme from the DNA sequence. Knowledge of the exact amino terminus was necessary before accurate expression of active enzyme could be attempted. Therefore, we purified the HGPRTase from crude extracts of the adult worms. The purified enzyme has a subunit molecular mass of 26 kDa and an amino terminal sequence of Met-Ser-Ser-Asn-Met. This sequence matched one of the potential initiation sites predicted from the cDNA and gene sequence. We next expressed the correct size cDNA of the S. mansoni HGPRTase in Escherichia coli using a vector that is regulated by a bacterial alkaline phosphatase promoter and uses an E. coli signal peptide for secretion of expressed product into the periplasmic space. Using this expression system, some of the recombinant enzyme is secreted and found to have a correct amino terminus. That remaining in the cytoplasm has part of the signal peptide attached to the amino terminus. The recombinant schistosomal HGPRTase isolated from the periplasm of the transformed E. coli was purified and found to have kinetic and physical properties identical to those of the native enzyme. PMID- 2199440 TI - Expression, purification, and crystallization of natural and selenomethionyl recombinant ribonuclease H from Escherichia coli. AB - Ribonuclease H (RNase H) from Escherichia coli is an endonuclease that specifically degrades the RNAs of RNA:DNA hybrids. The enzyme is a single polypeptide chain of 155 amino acid residues, of which 4 are methionines. To solve the crystallographic three-dimensional structure of E. coli RNase H by the multi-wavelength anomalous diffraction technique, we have constructed methionine auxotrophic strains of E. coli that overexpress selenomethionyl RNase H. MIC88 yields about 10 mg of selenomethionyl RNase H per liter of culture, which is comparable to the overexpression of the natural recombinant protein. We have purified both proteins to homogeneity and crystallized them isomorphously in the presence of sulfate. These are Type I crystals of space group P2(1)2(1)2(1) with the cell parameters a = 41.8 A, b = 86.4 A, c = 36.4 A, one monomer per asymmetric unit, and approximately 36% (v/v) solvent. Crystals of both proteins diffract to beyond 2-A Bragg spacings and are relatively durable in an x-ray beam. On replacement of sulfate with NaCl, crystals of natural RNase H grow as Type I' (very similar to Type I) at pH between 7.0 and 8.0; at pH 8.8, crystals of Type II are obtained in space group P2(1)2(1)2(1) with a = 44.3 A, b = 87.3 A, and c = 35.7 A. Type II crystals can be converted to Type I by soaking in phosphate buffer. RNase H crystals of Type II have also been reported by Kanaya et al. (Kanaya, S., Kohara, A., Miyakawa, M., Matsuzaki, T., Morikawa, K., and Ikehara, M. (1989) J. Biol. Chem. 264, 11546-11549). PMID- 2199441 TI - In vitro synthesis of chlorophyll a in the dark triggers accumulation of chlorophyll a apoproteins in barley etioplasts. AB - An in vitro translation system using lysed etioplasts was developed to test if the accumulation of plastid-encoded chlorophyll a apoproteins is dependent on the de novo synthesis of chlorophyll a. The P700 apoproteins, CP47 and CP43, were not radiolabeled in pulsechase translation assays employing lysed etioplasts in the absence of added chlorophyll precursors. When chlorophyllide a plus phytylpyrophosphate were added to lysed etioplast translation assays in the dark, chlorophyll a was synthesized and radiolabeled P700 apoproteins, CP47 and CP43, and a protein which comigrates with D1 accumulated. Chlorophyllide a or phytylpyrophosphate added separately to the translation assay in darkness did not induce chlorophyll a formation or chlorophyll a apoprotein accumulation. Chlorophyll a formation and chlorophyll a apoprotein accumulation were also induced in the lysed etioplast translation system by the photoreduction of protochlorophyllide to chlorophyllide a in the presence of exogenous phytylpyrophosphate. Accumulation of radiolabeled CP47 was detectable when very low levels of chlorophyll a were synthesized de novo (less than 0.01 nmol/10(7) plastids), and radiolabel increased linearly with increasing de novo chlorophyll a formation. Higher levels of de novo synthesized chlorophyll a were required prior to detection of radiolabel incorporation into the P700 apoproteins and CP43 (greater than 0.01 nmol/10(7) plastids). Radiolabel incorporation into the P700 apoproteins, CP47 and CP43, saturated at a chlorophyll a concentration which corresponds to 50% of the etioplast protochlorophyllide content (0.06 nmol of chlorophyll a/10(7) plastids). PMID- 2199442 TI - Characterization and expression of the unique calmodulin gene of Aspergillus nidulans. AB - Complete cDNA and genomic clones for the unique calmodulin (CaM) gene of the filamentous fungus Aspergillus nidulans have been isolated and characterized. The gene contains five introns, of which three are at unique positions relative to other CaM genes. The A. nidulans CaM gene is transcribed as a single, 0.85 kilobase mRNA species that encodes a predicted protein 84% identical (93% similar if conservative changes are considered) to vertebrate CaM. The complete cDNA was ligated into a lambda PL promoter-regulated bacterial expression vector to allow expression of A. nidulans CaM in Escherichia coli. The expressed protein was purified from bacterial lysates by phenyl-Sepharose chromatography and migrated as a single species on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In the presence of Ca2+, A. nidulans CaM exhibited a shift in apparent Mr identical to vertebrate CaM. The bacterially synthesized protein activated vertebrate CaM-dependent phosphodiesterase, CaM-dependent protein kinase II, and myosin light chain kinase with kinetics similar to vertebrate CaM. Isolated conidia (G0 spores) were germinated to induce synchronous cell cycle re-entry and the levels of CaM mRNA and protein determined. Both CaM and its mRNA were regulated during cell cycle re-entry. Calmodulin mRNA levels increased 20-fold as germlings progressed through the G1 phase, while CaM levels increased 2-fold prior to the initiation of DNA synthesis. Messenger RNA levels decreased during S phase while protein levels increased an additional 2-fold, peaking at the onset of mitosis followed by a subsequent decrease as cells completed mitosis. Disruption of the CaM gene by site-specific homologous recombination was lethal, indicating that CaM is essential for cell cycle progression. PMID- 2199443 TI - Insulin regulation of the two glucose transporters in 3T3-L1 adipocytes. AB - The amounts of the brain type and muscle type glucose transporters (designated Glut 1 and 4, respectively) in 3T3-L1 adipocytes have been determined by quantitative immunoblotting with antibodies against their carboxyl-terminal peptides. There are about 950,000 and 280,000 copies of Glut 1 and 4, respectively, per cell. Insulin caused the translocation of both types of transporters from an intracellular location to the plasma membrane. The insulin elicited increase in cell surface transporters was assessed by labeling the surface transporters with a newly developed, membrane-impermeant, photoaffinity labeling reagent for glucose transporters. The increases in Glut 1 and 4 averaged 6.5- and 17-fold, respectively, whereas there was a 21-fold in hexose transport. These results indicate that the translocation of Glut 4 could largely account for the insulin effect on transport rate, but only if the intrinsic activity of Glut 4 is much higher than that of Glut 1. The two transporters are colocalized intracellularly: vesicles (average diameter 72 nm) isolated from the intracellular membranes by immunoadsorption with antibodies against Glut 1 contained 95% of the Glut 4 and, conversely, vesicles isolated with antibodies against Glut 4 contained 85% of the Glut 1. PMID- 2199444 TI - The fidelity of DNA synthesis catalyzed by derivatives of Escherichia coli DNA polymerase I. AB - The fidelity of DNA synthesis by an exonuclease-proficient DNA polymerase results from the selectivity of the polymerization reaction and from exonucleolytic proofreading. We have examined the contribution of these two steps to the fidelity of DNA synthesis catalyzed by the large Klenow fragment of Escherichia coli DNA polymerase I, using enzymes engineered by site-directed mutagenesis to inactivate the proofreading exonuclease. Measurements with two mutant Klenow polymerases lacking exonuclease activity but retaining normal polymerase activity and protein structure demonstrate that the base substitution fidelity of polymerization averages one error for each 10,000 to 40,000 bases polymerized, and can vary more than 30-fold depending on the mispair and its position. Steady state enzyme kinetic measurements of selectivity at the initial insertion step by the exonuclease-deficient polymerase demonstrate differences in both the Km and the Vmax for incorrect versus correct nucleotides. Exonucleolytic proofreading by the wild-type enzyme improves the average base substitution fidelity by 4- to 7 fold, reflecting efficient proofreading of some mispairs and less efficient proofreading of others. The wild-type polymerase is highly accurate for -1 base frameshift errors, with an error rate of less than or equal to 10(-6). The exonuclease-deficient polymerase is less accurate, suggesting that proofreading also enhances frameshift fidelity. Even without a proofreading exonuclease, Klenow polymerase has high frameshift fidelity relative to several other DNA polymerases, including eucaryotic DNA polymerase-alpha, an exonuclease-deficient, 4-subunit complex whose catalytic subunit is almost three times larger. The Klenow polymerase has a large (46 kDa) domain containing the polymerase active site and a smaller (22 kDa) domain containing the active site for the 3'----5' exonuclease. Upon removal of the small domain, the large polymerase domain has altered base substitution error specificity when compared to the two-domain but exonuclease-deficient enzyme. It is also less accurate for -1 base errors at reiterated template nucleotides and for a 276-nucleotide deletion error. Thus, removal of a protein domain of a DNA polymerase can affect its fidelity. PMID- 2199445 TI - Human recombinant factor XIII from Saccharomyces cerevisiae. Crystallization and preliminary x-ray data. AB - Crystals of human recombinant factor XIII from the yeast Saccharomyces cerevisiae have been grown from solutions of ammonium sulfate at pH 5.8. The crystals are orthorhombic, with space group P2(1)2(1)2 and unit cell dimensions gamma a = 101.2, b = 182.7, and c = 93.4 A. The asymmetric unit consists of one a2 dimer of molecular mass 166 kDa. A 3.5-A resolution data set for the native protein has been collected. Practical resolution limits for these crystals have not been determined, but reflections have been observed to a Bragg spacing of 2.8-A resolution. PMID- 2199446 TI - Recombinant HIV2 protease processes HIV1 Pr53gag and analogous junction peptides in vitro. AB - A synthetic DNA fragment encoding a protease precursor of the human immunodeficiency virus type 2 (HIV2) was cloned and expressed in bacteria and yeast. A recombinant plasmid encoding a hybrid polypeptide consisting of human superoxide dismutase and an HIV2 protease precursor of 113 amino acids was constructed for regulated intracellular expression in bacteria. Induction of this plasmid produced an autoprocessed form of the retroviral enzyme possessing the correct molecular weight. Overexpression and secretion of the protease from yeast was achieved with an expression vector encoding the yeast pheromone alpha-factor signal/leader sequence fused to a protease precursor of 115 amino acids. Amino terminal sequence analysis confirmed that the viral enzyme exported from yeast was correctly processed from its precursor by cleavage of the predicted Ala-Pro peptide bond located at the NH2 terminus of the protease in the pol open reading frame. No additional amino acid residues were required at the COOH terminus of the protease for this autoproteolytic event. The HIV2 protease expressed in bacteria and yeast was active in an in vitro assay when tested on the HIV1 polyprotein precursor, myristylated Pr53gag. Two synthetic peptides representing junction sequences in the HIV1 gag-pol precursor were used to assay purified HIV2 protease. The enzyme exhibited a kcat/KM of 23.2 min-1 mM-1 on the HIV1 matrix capsid junction peptide and a kcat/KM of 71.4 min-1 mM-1 on the protease-reverse transcriptase junction peptide. These rates show that the HIV2 enzyme is efficient at hydrolyzing the HIV1 peptide junctions, revealing the analogous nature of the substrate specificities of the two enzymes. PMID- 2199447 TI - Resolution of Holliday junction analogs by T4 endonuclease VII can be directed by substrate structure. AB - Endonuclease VII is an enzyme from bacteriophage T4 capable of resolving four-arm Holliday junction intermediates in recombination. Since natural Holliday junctions have homologous (2-fold) sequence symmetry, they can branch migrate, creating a population of substrates that have the branch point at different sites. We have explored the substrate requirements of endonuclease VII by using immobile analogs of Holliday junctions that lack this homology, thereby situating the branch point at a fixed site in the molecule. We have found that immobile junctions whose double-helical arms contain fewer than nine nucleotide pairs do not serve as substrates for resolution by endonuclease VII. Scission of substrates with 2-fold symmetrically elongated arms produces resolution products that are a function of the particular arms that are lengthened. We have confirmed that the scission products are those of resolution, rather than nicking of individual strands, by using shamrock junction molecules formed from a single oligonucleotide strand. A combination of end-labeled and internally labeled shamrock molecules has been used to demonstrate that all of the scission is due to coordinated cleavage of DNA on opposite sides of the junction, 3' to the branch point. Endonuclease VII is known to cleave the crossover strands of Holliday junctions in this fashion. The relationship of the long arms to the cleavage direction suggests that the portion of the enzyme which requires the minimum arm length interacts with the pair of arms containing the 3' portion of the crossover strands on the bound surface of the antiparallel junction. PMID- 2199448 TI - Phosphorylation of a neuronal-specific beta-tubulin isotype. AB - Adult rats were intracraneally injected with [32P] phosphate and brain microtubules isolated. The electrophoretically purified, in vivo phospholabeled, beta-tubulin was digested with the V8-protease and the labeled peptide purified by reversed-phase liquid chromatography. Its amino acid sequence corresponds to the COOH-terminal sequence of a minor neuronal beta 3-tubulin isoform from chicken and human. The phosphorylation site was at serine 444. A synthetic peptide with sequence EMYEDDEEESESQGPK, corresponding to that of the COOH terminus of beta 3-tubulin, was efficiently phosphorylated in vitro by casein kinase II at the same serine 444. The functional meaning of tubulin phosphorylation is still unclear. However, the modification of the protein takes place after microtubule assembly, and phosphorylated tubulin is mainly present in the assembled microtubule protein fraction. PMID- 2199449 TI - Three-dimensional structure of thymidine phosphorylase from Escherichia coli at 2.8 A resolution. AB - The three-dimensional structure of thymidine phosphorylase from Escherichia coli has been determined at 2.8 A resolution using multiple-isomorphous-replacement techniques. The amino acid sequence deduced from the deoA DNA sequence is also reported. Thymidine phosphorylase exists in the crystal as an S-shaped dimer in which the subunits are related by a crystallographic 2-fold axis. Each subunit is composed of a small alpha-helical domain of six helices and a large alpha/beta domain. The alpha/beta domain includes a six-stranded mixed beta-sheet and a four stranded antiparallel beta-sheet. The active site has been identified by difference Fourier analyses of the binding of thymine and thymidine and lies in a cavity between the small and large domains. The central beta-sheet is splayed open to accommodate a putative phosphate-binding site which is probably occupied by a sulfate ion in the crystal. PMID- 2199450 TI - Physicochemical properties of the lipopolysaccharide unit that activates B lymphocytes. AB - We have examined the physical state of highly purified deep rough chemotype lipopolysaccharide (ReLPS) from Escherichia coli D31m4 as an aqueous suspension and as complexes with bovine serum albumin min (BSA). The ReLPS suspension showed large ellipsoidal particles 12-38 nm wide and 40-100 nm long. The solubility of this form of ReLPS was determined by equilibrium dialysis experiments to be 3.3 x 10(-8) M at 22 degrees C and 2.8 x 10(-8) M at 37 degrees C in 150 mM Tris-KCl, pH 7.5; 3.0 x 10(-8) M at 37 degrees C in 0.75 mM Tris-KCl, pH 7.5. The BSA-ReLPS complexes were fractionated on a Sephacryl S-200 column to yield peaks I and II with apparent masses of about 240 and 70 kDa, respectively. Peak II was a BSA monomer with estimated BSA:ReLPS molar ratios of 1:1-1:7. The ReLPS suspension and the two complexes were compared as antigens in enzyme-linked immunosorbent assays using three select monoclonal antibodies to lipopolysaccharide. The results were consistent with the high state of disaggregation of the ReLPS in both peaks I and II. Since the ReLPS in these complexes were not visible by electron microscopy, they did not contain vesicles or large particles. All forms of ReLPS tested were capable of stimulating 70Z/3, a lipopolysaccharide responsive murine pre-B cell line. However, peak II was consistently more stimulatory at very low concentrations than the other preparations. The maximally stimulatory concentration of ReLPS for 70Z/3 cells was 40 ng/ml (1.6 x 10(-8) M) for peak II and 70 ng/ml (2.8 x 10(-8) M) for the ReLPS suspension. As expected, the above concentrations were at or below the solubility of the ReLPS. These results suggested that the highly disaggregated form of ReLPS (possibly the monomer) is the active unit that stimulates the cellular response in 70Z/3 cells. PMID- 2199451 TI - Ultrasound examination of the irritable hip. AB - We made a prospective study of 111 children with acute hip pain to assess whether ultrasound can replace traditional radiography. An effusion was diagnosed in 71% by ultrasound but in only 15% by radiography. This effusion persisted for a mean of nine days; symptoms lasted for five days. Two patients found to have Perthes' disease had longer-lasting effusion and symptoms. Patients without an effusion had no obvious cause for their pain, so the pressure of an effusion from a transient synovitis does not account for all patients with irritable hips. Patients with an effusion persisting for over 24 days (the mean + 2 s.d. of our series) had more symptoms, a significantly larger effusion and greater limitation of movement. They may be more at risk for avascular necrosis. We found that radiographic examination influenced the immediate management of only two patients, those with Perthes' disease. We therefore propose a protocol of management for irritable hip, using ultrasonography at the first presentation of certain categories of patients. This would reduce the number of early radiographs by 75%. PMID- 2199452 TI - Foreign-body reactions to fracture fixation implants of biodegradable synthetic polymers. AB - Biodegradable rods of polyglycolide or lactide-glycolide copolymer were used in the internal fixation of a variety of fractures and osteotomies in 516 patients. A clinically manifest foreign-body reaction occurred in 41 patients (7.9%), producing a fluctuant swelling at the implantation site after an average of 12 weeks. Spontaneous sinus formation or surgical drainage yielded a sterile exudate containing liquid remnants of the degrading implants. After prompt drainage this discharge subsided within three weeks. Histological examination showed a typical nonspecific foreign-body reaction with abundant giant cells both in patients with the reaction and in some patients with an uneventful clinical course. The factors determining the nature of the reaction were probably related to the local capacity of the tissues to clear the polymeric debris. The reactions did not influence the clinical or radiographic results, but recognition of the incidence and the features of the reaction is necessary in view of the increasing use of such implants. PMID- 2199453 TI - Primary migration of fully-threaded acetabular prostheses. A roentgen stereophotogrammetric analysis. AB - We investigated the fixation of fully-threaded cementless acetabular prostheses in 20 patients with osteoarthritis, measuring the migration of the cup using roentgen stereophotogrammetric analysis (RSA). All the cups migrated proximally, 13 moved laterally or medially, and nine moved anteriorly or posteriorly in the first two postoperative years, the average migration being 1.1 to 1.4 mm in either direction. Rotatory movements of up to 5.7 degrees were found in nine of the 13 hips where this analysis could be performed. Movements of cobalt-chrome (12) and titanium alloy (8) cups did not differ significantly. Seventeen of the 20 patients had some pain two years after the operation. The migration of the prostheses indicates that 'osseointegration' had not occurred. The combination of this with persistent pain suggests that the long-term results will be unfavourable. PMID- 2199454 TI - Tissue-specific sorting of the human LDL receptor in polarized epithelia of transgenic mice. AB - The distribution of human low density lipoprotein (LDL) receptors was studied by immunofluorescence and immunoelectron microscopy in epithelial cells of transgenic mice that express high levels of receptors under control of the metallothionein-I promoter. In hepatocytes and intestinal epithelial cells, the receptors were confined to the basal and basolateral surfaces, respectively. Very few LDL receptors were present in coated pits or intracellular vesicles. In striking contrast, in the epithelium of the renal tubule the receptors were present on the apical (lumenal) surface where they appeared to be concentrated at the base of microvilli and were abundant in vesicles of the endocytic recycling pathway. Intravenously administered LDL colloidal gold conjugates bound to the receptors on hepatocyte microvilli and were slowly internalized, apparently through slow migration into coated pits. We conclude that (a) sorting of LDL receptors to the surface of different epithelial cells varies with each tissue; and (b) in addition to a signal for clustering in coated pits, the LDL receptor may contain a signal for retention in noncoated membrane that is manifest in hepatocytes and intestinal epithelial cells, but not in renal epithelial cells or cultured human fibroblasts. PMID- 2199455 TI - Yeast carboxypeptidase Y vacuolar targeting signal is defined by four propeptide amino acids. AB - The amino-terminal propeptide of carboxypeptidase Y (CPY) is necessary and sufficient for targeting this glycoprotein to the vacuole of Saccharomyces cerevisiae. A 16 amino acid stretch of the propeptide was subjected to region directed mutagenesis using randomized oligonucleotides. Mutations altering any of four contiguous amino acids, Gln-Arg-Pro-Leu, resulted in secretion of the encoded CPY precursor (proCPY), demonstrating that these residues form the core of the vacuolar targeting signal. Cells that simultaneously synthesize both wild type and sorting-defective forms of proCPY efficiently sort and deliver only the wild-type molecule to the vacuole. These results indicate that the PRC1 missorting mutations are cis-dominant, implying that the mutant forms of proCPY are secreted as a consequence of failing to interact with the sorting apparatus, rather than a general poisoning of the vacuolar protein targeting system. PMID- 2199456 TI - Recycling of proteins from the Golgi compartment to the ER in yeast. AB - In the yeast Saccharomyces cerevisiae, the carboxyl terminal sequence His-Asp-Glu Leu (HDEL) has been shown to function as an ER retention sequence (Pelham, H. R. B., K. G. Hardwick, and M. J. Lewis. 1988. EMBO (Eur. Mol. Biol. Organ.) J. 7:1757-1762). To examine the mechanism of retention of soluble ER proteins in yeast, we have analyzed the expression of a preproalpha factor fusion protein, tagged at the carboxyl terminus with the HDEL sequence. We demonstrate that this fusion protein, expressed in vivo, accumulates intracellularly as a precursor containing both ER and Golgi-specific oligosaccharide modifications. The Golgi specific carbohydrate modification, which occurs in a SEC18-dependent manner, consists of alpha 1-6 mannose linkages, with no detectable alpha 1-3 mannose additions, indicating that the transit of the HDEL-tagged fusion protein is confined to an early Golgi compartment. Results obtained from the fractionation of subcellular organelles from yeast expressing HDEL-tagged fusion proteins suggest that the Golgi-modified species are present in the ER. Overexpression of HDEL-tagged preproalpha factor results in the secretion of an endogenous HDEL containing protein, demonstrating that the HDEL recognition system can be saturated. These results support the model in which the retention of these proteins in the ER is dependent on their receptor-mediated recycling from the Golgi complex back to the ER. PMID- 2199457 TI - A rapid posttranslational myristylation of a 68-kD protein in D. discoideum. AB - Cells incubated with [3H]myristate were shown to rapidly and specifically acylate a 68-kD protein, p68, in a developmentally-regulated manner. The fatty acid incorporated into p68 was identified as myristate, and is linked to the protein via an amide bond, apparently to an NH2-terminal glycine. The acylation of p68 in D. discoideum displays some unusual properties. Unexpectedly, myristylation of p68 is a posttranslational event and occurs in the presence of inhibitors of protein synthesis. Another unusual finding was that although p68 is a stable protein, the acyl moiety is removed with a half time of approximately 15 min. PMID- 2199458 TI - Individual microtubules in the axon consist of domains that differ in both composition and stability. AB - We have explored the composition and stability properties of individual microtubules (MTs) in the axons of cultured sympathetic neurons. Using morphometric means to quantify the MT mass remaining in axons after various times in 2 micrograms/ml nocodazole, we observed that approximately 48% of the MT mass in the axon is labile, depolymerizing with a t1/2 of approximately 5 min, whereas the remaining 52% of the MT mass is stable, depolymerizing with a t1/2 of approximately 240 min. Immunofluorescence analyses show that the labile MTs in the axon are rich in tyrosinated alpha-tubulin, whereas the stable MTs contain little or no tyrosinated alpha-tubulin and are instead rich in posttranslationally detyrosinated and acetylated alpha-tubulin. These results were confirmed quantitatively by immunoelectron microscopic analyses of the distribution of tyrosinated alpha-tubulin among axonal MTs. Individual MT profiles were typically either uniformly labeled for tyrosinated alpha-tubulin all along their length, or were completely unlabeled. Roughly 48% of the MT mass was tyrosinated, approximately 52% was detyrosinated, and approximately 85% of the tyrosinated MTs were depleted within 15 min of nocodazole treatment. Thus, the proportion of MT profiles that were either tyrosinated or detyrosinated corresponded precisely with the proportion of MTs that were either labile or stable respectively. We also observed MT profiles that were densely labeled for tyrosinated alpha-tubulin at one end but completely unlabeled at the other end. In all of these latter cases, the tyrosinated, and therefore labile domain, was situated at the plus end of the MT, whereas the detyrosinated, and therefore stable domain was situated at the minus end of the MT, and in each case there was an abrupt transition between the two domains. Based on the frequency with which these latter MT profiles were observed, we estimate that minimally 40% of the MTs in the axon are composite, consisting of a stable detyrosinated domain in direct continuity with a labile tyrosinated domain. The extreme drug sensitivity of the labile domains suggests that they are very dynamic, turning over rapidly within the axon. The direct continuity between the labile and stable domains indicates that labile MTs assemble directly from stable MTs. We propose that stable MTs act as MT nucleating structures that spatially regulate MT dynamics in the axon. PMID- 2199459 TI - A monoclonal antibody to a mitotic microtubule-associated protein blocks mitotic progression. AB - A monoclonal antibody raised against mitotic spindles isolated from CHO cells ([CHO1], Sellitto, C., and R. Kuriyama. 1988. J. Cell Biol. 106:431-439) identifies an epitope that resides on polypeptides of 95 and 105 kD and is localized in the spindles of diverse organisms. The antigen is distributed throughout the spindle at metaphase but becomes concentrated in a progressively narrower zone on either side of the spindle midplane as anaphase progresses. Microinjection of CHO1, either as an ascites fluid or as purified IgM, results in mitotic inhibition in a stage-specific and dose-dependent manner. Parallel control injections with nonimmune IgMs do not yield significant mitotic inhibition. Immunofluorescence analysis of injected cells reveals that those which complete mitosis display normal localization of CHO1, whereas arrested cells show no specific localization of the CHO1 antigen within the spindle. Immunoelectron microscopic images of such arrested cells indicate aberrant microtubule organization. The CHO1 antigen in HeLa cell extracts copurifies with taxol-stabilized microtubules. Neither of the polypeptides bearing the antigen is extracted from microtubules by ATP or GTP, but both are approximately 60% extracted with 0.5 M NaCl. Sucrose gradient analysis reveals that the antigens sediment at approximately 11S. The CHO 1 antigen appears to be a novel mitotic MAP whose proper distribution within the spindle is required for mitosis. The properties of the antigen(s) suggest that the corresponding protein(s) are part of the mechanism that holds the antiparallel microtubules of the two interdigitating half spindles together during anaphase. PMID- 2199460 TI - The molecular cloning and identification of a gene product specifically required for nuclear movement in Aspergillus nidulans. AB - A temperature-sensitive mutation in the nudC gene (nudC3) of Aspergillus nidulans specifically prevents the microtubule-based movement of nuclei in this organism at the restrictive temperature. The mutation does not affect short term growth, nuclear division, or the movement of other subcellular organelles. Immunofluorescence analysis of cells blocked at the restrictive temperature, using antitubulin antibodies, shows that the inability of nuclei to move under these conditions is not related to an inability of a particular class of microtubule to form. The inability to move nuclei in this mutant is also shown to be independent of both mitosis and the number of nuclei in the cell as a double mutant carrying both nudC3 and a cell cycle-specific mutation blocks with a single immotile nucleus at the restrictive temperature. The molecular cloning of the nudC gene and sequence analysis reveal that it encodes a previously unidentified protein of 22 kd. Affinity-purified antisera reactive to the nudC protein cross reacts to a single protein of 22 kD in Aspergillus protein extracts. This purified sera failed to reveal a subcellular location for the nudC protein at the level of indirect immunofluorescence. The data presented suggest that the 22-kD nudC gene product functions by interacting between microtubules and nuclei and/or is involved in the generation of force used to move nuclei during interphase. PMID- 2199461 TI - A protein antigenically related to nuclear lamin B mediates the association of intermediate filaments with desmosomes. AB - Desmosomes are specialized domains of epithelial cell plasma membranes engaged in the anchoring of intermediate filaments (IF). So far, the desmosomal component(s) responsible for this binding has not been unambiguously identified. In the present work, we have examined bovine muzzle epidermis desmosomes for the presence of protein(s) structurally and functionally related to lamin B, the major receptor for IF in the nuclear envelope (Georgatos, S. D., and G. Blobel. 1987. J. Cell Biol. 105:105-115). By using polyclonal antibodies to lamin B in immunoblotting experiments, we find that a desmosomal protein of 140-kD shares epitope(s) with lamin B. Immunoelectron microscopic and urea extraction experiments show that this protein is a peripheral protein localized at the cytoplasmic side of the desmosomes (desmosomal plaques). Furthermore, this protein binds vimentin in an in vitro assay. Since this binding is inhibited by lamin B antibodies, the epitopes common to the 140-kD protein and to lamin B may be responsible for anchoring of intermediate filaments to desmosomes. These data suggest that lamin B-related proteins (see also Cartaud, A., J. C. Courvalin, M. A. Ludosky, and J. Cartaud. 1989. J. Cell Biol. 109:1745-1752) together with lamin B, provide cells with several nucleation sites, which can account for the multiplicity of IF organization in tissues. PMID- 2199462 TI - Extracellular matrix-associated molecules collaborate with ciliary neurotrophic factor to induce type-2 astrocyte development. AB - O-2A progenitor cells give rise to both oligodendrocytes and type-2 astrocytes in vitro. Whereas oligodendrocyte differentiation occurs constitutively, type-2 astrocyte differentiation requires extracellular signals, one of which is thought to be ciliary neurotrophic factor (CNTF). CNTF, however, is insufficient by itself to induce the development of stable type-2 astrocytes. In this report we show the following: (a) that molecules associated with the extracellular matrix (ECM) cooperate with CNTF to induce stable type-2 astrocyte differentiation in serum-free cultures. The combination of CNTF and the ECM-associated molecules thus mimics the effect of FCS, which has been shown previously to induce stable type-2 astrocyte differentiation in vitro. (b) Both the ECM-associated molecules and CNTF act directly on O-2A progenitor cells and can induce them to differentiate prematurely into type-2 astrocytes. (c) ECM-associated molecules also inhibit oligodendrocyte differentiation, even in the absence of CNTF, but this inhibition is not sufficient on its own to induce type-2 astrocyte differentiation. (d) Whereas the effect of ECM on oligodendrocyte differentiation is mimicked by basic fibroblast growth factor (bFGF), the effect of ECM on type-2 astrocyte differentiation is not. (e) The ECM-associated molecules that are responsible for inhibiting oligodendrocyte differentiation and for cooperating with CNTF to induce type-2 astrocyte differentiation are made by non-glial cells in vitro. (f) Molecules that have these activities and bind to ECM are present in the optic nerve at the time type-2 astrocytes are thought to be developing. PMID- 2199464 TI - Colony stimulating factor-1 is a negative regulator of the macrophage respiratory burst. AB - Several cytokines have previously been shown to prime macrophages for enhanced release of oxygen radicals in response to subsequent stimulation. We now demonstrate that the presence of the macrophage-specific colony stimulating factor-1 (CSF-1) inhibits the priming of murine macrophages by a variety of agents including tumor necrosis factor alpha, granulocyte/macrophage colony stimulating factor, interferon-gamma, and bacterial lipopolysaccharide. CSF-1 is also able to reduce the respiratory burst in the absence of priming. Our results indicate that CSF-1 is a potent negative regulator of the macrophage respiratory burst which acts to oppose the priming (enhancing) action of macrophage activating agents. We propose that CSF-1 may have a potentially important and previously unrecognized, role as a physiological regulator which restricts or terminates the activation of macrophages in order to prevent an uncontrolled inflammatory reaction. PMID- 2199463 TI - Differentiation expression during proliferative activity induced through different pathways: in situ hybridization study of thyroglobulin gene expression in thyroid epithelial cells. AB - In canine thyrocytes in primary culture, our previous studies have identified three mitogenic agents and pathways: thyrotropin (TSH) acting through cyclic AMP (cAMP), EGF and its receptor tyrosine protein kinase, and the phorbol esters that stimulate protein kinase C. TSH enhances, while EGF and phorbol esters inhibit, the expression of differentiation. Given that growth and differentiation expression are often considered as mutually exclusive activities of the cells, it was conceivable that the differentiating action of TSH was restricted to noncycling (Go) cells, while the inhibition of the differentiation expression by EGF and phorbol esters only concerned proliferating cells. Therefore, the capacity to express the thyroglobulin (Tg) gene, the most prominent marker of differentiation in thyrocytes, was studied in proliferative cells (with insulin) and in quiescent cells (without insulin). Using cRNA in situ hybridization, we observed that TSH (and, to a lesser extent, insulin and insulin-like growth factor I) restored or maintained the expression of the Tg gene. Without these hormones, the Tg mRNA content became undetectable in most of the cells. EGF and 12-0-tetradecanoyl phorbol-13-acetate (TPA) inhibited the Tg mRNA accumulation induced by TSH (and/or insulin). Most of the cells (up to 90%) responded to both TSH and EGF. Nevertheless, the range of individual response was quite variable. The effects of TSH and EGF on differentiation expression were not dependent on insulin and can therefore be dissociated from their mitogenic effects. Cell cycling did not affect the induction of Tg gene. Indeed, the same cell distribution of Tg mRNA content was observed in quiescent cells stimulated by TSH alone, or in cells approximately 50% of which had performed one mitotic cycle in response to TSH + insulin. Moreover, after proliferation in "dedifferentiating" conditions (EGF + serum + insulin), thyrocytes had acquired a fusiform fibroblast like morphology, and responded to TSH by regaining a characteristic epithelial shape and high Tg mRNA content. 32 h after the replacement of EGF by TSH, cells in mitosis presented the same distribution of the Tg mRNA content as the rest of the cell population. This implies that cell cycling (at least 27 h, as previously shown) did not affect the induction of the Tg gene which is clearly detectable after a time lag of at least 24 h. The data unequivocally show that the reexpression of differentiation and proliferative activity are separate but fully compatible processes when induced by cAMP in thyrocytes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2199465 TI - Stimulating effects of insulin and low-density lipoprotein on cell growth and macromolecular syntheses of HeLa cells cultured in K(+)-depleted medium. AB - The influence of the intracellular K+ concentration on the effects of growth factors (insulin, EGF, hydrocortisone, and transferrin) and LDL on growth of HeLa cells was investigated. Upon replacement of K+ in a chemically defined medium (K(+)-CDM) by Rb+ (Rb(+)-CDM), about 80% of the intracellular K+ was replaced by Rb+ within 24 h, but showed no further change in the next 24 h, irrespective of addition of dialyzed calf serum (5%) or growth factors to the medium. In Rb(+) CDM, cell growth and DNA synthesis were greatly suppressed, although cell viability was not significantly altered for 72 h. The suppression of cell growth was partially restored by addition of serum, insulin (5 micrograms/ml), or LDL (2.5 mg/ml) to Rb(+)-CDM. A combination of serum and insulin or insulin and LDL stimulated cell growth to approximately the level in K(+)-CDM without any addition, but a combination of serum and LDL did not have more effect than that of serum alone. Unexpectedly, other factors were ineffective in stimulating growth in Rb(+)-CDM. In Rb(+)-CDM, the effect of insulin was lost in 24-48 h, whereas that of LDL persisted for at least 96 h. Insulin and LDL also enhanced growth in K(+)-CDM. After cessation of cell growth in Rb(+)-CDM for 24 h, addition of insulin and/or LDL markedly restored cell growth and DNA synthesis. Therefore, insulin and LDL may stimulate certain mechanisms required for cell growth that can operate in K(+)-deficient conditions. PMID- 2199466 TI - Plasminogen activators and their inhibitors in the neuromuscular system: I. Developmental regulation of plasminogen activator isoforms during in vitro myogenesis in two cell lines. AB - Plasminogen activators (PAs), were estimated qualitatively and quantitatively in two different clonal murine skeletal muscle cell lines. Both cell lines produced the two major types of PAs found in mammalian cells, urokinase-type (uPA) and tissue type (tPA). These two lines are models for the study of myogenesis in vitro, but differ in several growth and differentiation characteristics. Because of their possible involvement in these characteristics we assayed the expression of PAs in both cell systems during development in culture. Utilizing fibrin zymography two isoforms of tPA were detected. One co-migrated with human tPA at 75 kd and another may represent a tPA:inhibitor complex at 105 Kd. Several isoenzymes of uPA were detected and these changed depending on whether cell homogenates or conditioned medium was analyzed and whether myogenic cells were at single-cell myoblast or multi-nucleated myotube stage. Species-specific antisera to mouse uPA identified 4 uPA bands in muscle cell medium and 5 in cell layers. Antigenic uPA bands also varied depending on stage of myogenesis. Quantitative amidolytic studies using chromogenic substrates showed that maximal PA activity, both uPA and tPA, occurred at the time of myoblast fusion. Furthermore, uPA activity in membranes increased during myogenesis, while both uPA and tPA in medium decreased after fusion. These studies indicate that muscle PA expression is developmentally regulated and may correlate with growth and differentiation in skeletal muscle. PMID- 2199467 TI - Expression and regulation of pOb24 and lipoprotein lipase genes during adipose conversion. AB - Lipoprotein lipase (LPL) and pOb24 mRNAs are known to be early markers of adipose cell differentiation. Comparative studies of the expression of pOb24 and LPL genes during adipose conversion of Ob1771 preadipocyte cells and in mouse adipose tissue have shown the following: 1) the expression of both genes takes place at confluence; this event can also be triggered by growth arrest of exponentially growing cells at the G1/S stage of the cell cycle; 2) In contrast to glycerol-3 phosphate dehydrogenase mRNA, the emergence of pOb24 and lipoprotein lipase mRNAs requires neither growth hormone or tri-iodothyronine as obligatory hormones nor insulin as a modulating hormone; 3) in mouse adipose tissue, pOb24 mRNA is present at a high level in stromal-vascular cells and at a low level in mature adipocytes, and in contrast LPL mRNAs are preferentially expressed in mature adipocytes. Thus, these two genes do not appear to be regulated in a similar manner, as also shown by the differential inhibition of their expression by tumor necrosis factor (TNF) and transforming growth factor-beta (TGF-beta). PMID- 2199468 TI - Interaction of growth factors during progression towards steroid independence in T-47-D human breast cancer cells. AB - When deprived of steroid in the long term, T-47-D human breast cancer cells lose estrogen sensitivity of cell growth. This loss of response results from an increased basal growth rate in the absence of steroid, not from a loss of estrogen-stimulated growth, and it occurs without any loss of estrogen receptor number or function. Growth factor gene expression and sensitivity have been investigated in this model system in an attempt to unravel the molecular mechanisms underlying the progression to steroid autonomy. The transition was accompanied by a decreased dependence on added serum and by a loss of the stimulatory effects of insulin and basic fibroblast growth factor, but also by an acquired sensitivity to stimulation by transforming growth factor-beta (TGF beta). An increase in TGF-beta 1 mRNA was detected following loss of steroid sensitivity. There was no increase in epidermal growth factor (EGF) receptor number. These findings are discussed in relation to current knowledge concerning the mechanisms by which estrogens stimulate breast cancer cell proliferation. PMID- 2199469 TI - Neutral endopeptidase from nuchal ligament of fetal calves. AB - The nuchal ligament of unborn calves contains a neutral endopeptidase that is biochemically and immunologically similar to the neutral endopeptidase (NEP), or enkephalinase, from human kidney. Enzymatic activity was inhibited more than 90% by phosphoramidon (1 microM). The specific activity in membrane fractions, as determined by hydrolysis of the dansylated substrate, DAPGN, was similar in tissue from fetuses of gestational ages ranging from 100 to 280 days. NEP activity in adult ligament tissue, however, was less than 10% of that in fetal tissue. Fibroblasts dissociated from ligament tissue by collagenase displayed less NEP activity than did preparations of intact ligament, and activity was even lower in cultured cells. By contrast, fibroblasts cultured from fetal calf lungs had NEP activity comparable to that in the ligament tissue. When ligament fibroblasts were cultured on subcellular matrices derived from fetal lung fibroblasts the NEP activity increased relative to those cultured on plastic alone. These studies confirm the presence of neutral endopeptidase (NEP) in the nuchal ligament of the fetal calf. The consistent activity through a range of gestational ages and the influence of the subcellular matrix suggest that this enzyme might be involved in growth of the ligament during fetal life. PMID- 2199470 TI - On the pragmatics of contrast. AB - In this paper, I review properties and consequences of the PRINCIPLE OF CONTRAST. This principle, which I have argued from the beginning has a pragmatic basis, captures facts about the inferences speakers and addresses make for both conventional and novel words. Along with a PRINCIPLE OF CONVENTIONALITY, it accounts for the pre-emption of novel words by well-established ones. And it holds just as much for morphology as it does for words and larger expressions. In short, Contrast has the major properties Gathercole (1989) proposed as characteristic of her alternative to Contrast. PMID- 2199471 TI - An update on the CHILDES/BIB (formerly ISU/CHILDES) database. AB - A description is given of the CHILDES/BIB database, its contents, and its relationship to the CHILDES database. CHILDES is a depository of child language corpora, and the publisher of CHAT (a transcription manual), and CLAN (an electronic package for child language research). CHILDES/BIB is an electronic bibliographic database that is an autonomous unit of CHILDES. PMID- 2199472 TI - Use of high-performance liquid chromatography in the pharmaceutical industry. AB - Requirements for new pharmaceutical products and their impact on applications of high-performance liquid chromatography (HPLC) are discussed. The strengths and weaknesses of HPLC in this context are evaluated and compared with current trends and expectation in separation science. PMID- 2199473 TI - Combination of positron emission tomography with liquid chromatography in neuropharmacologic research. AB - Positron emission tomography (PET) is an in vivo autoradiographic technique that determines the radioactive distribution and kinetics of a radiolabelled tracer in a tissue. By choice of tracer, it is possible to study physiological processes in living animals and man non-invasively. PET has certain disadvantages such as limited spatial resolution and simultaneous measurement of radiolabelled tracer with the metabolites formed. For an adequate interpretation of the data obtained, complementary techniques such as column liquid chromatography of radioactive composition in blood, plasma, urine and tissue samples have to be used. The prerequisites for any chromatographic technique used for the radioanalysis of substances are speed, high selectivity and high separation efficiency. Examples from PET studies in combination with chromatographic analysis will be given. The utilization of L-dopa in the brain constitutes several steps. Analysis by column liquid chromatography of metabolites in plasma and in monkey brain tissue will make it possible to elucidate different utilization processes of the tracer. Kinetic studies of 11C-labelled neuropeptides such as methionine-enkephalin and substance P revealed high radioactivities in the brain of monkeys. However, simultaneous determination plasma and urine radioactivities using liquid chromatography with radiochemical and photometric detection both indicated that the brain radioactivities emanated to a large extent from 11C-labelled metabolites formed in vivo. Studies with PET using radiotracers having a rapid and extensive metabolism require complementary techniques in the evaluation. High detection selectivity, by combination of photometric and radiochemical detection and rapid and efficient separation, will make liquid chromatography a most important complement in the analysis. PMID- 2199474 TI - Documentation of the nursing process in an outpatient clinic. PMID- 2199475 TI - Clinical review 11: The rational use of growth hormone during childhood. PMID- 2199476 TI - Thyroid status in normal pregnancy. PMID- 2199477 TI - Genetic abnormalities in sporadic parathyroid adenomas. AB - We analyzed genomic DNA from 43 sporadic benign parathyroid adenomas for rearrangements of the PTH gene, and for point mutations of the H-ras (codons 12, 13, and 61), N-ras (codons 12, 13, and 61), and K-ras (codons 12 and 13) genes. One of 43 parathyroid adenomas showed a chromosome 11 rearrangement involving both the PTH gene on the short arm of chromosome 11 (at band p15) and a locus on the long arm (11q13). This rearrangement was indistinguishable from one that was previously described in a parathyroid adenoma by Arnold et al., indicating that this may be an important contributor to tumorigenesis in a small subset of patients with parathyroid adenoma. H-ras, K-ras, and N-ras oncogene activation by point mutation at codons 12, 13, or 61, known to occur in many tumors, could not be detected in any parathyroid adenoma. PMID- 2199478 TI - The 24-hour pattern of the levels of serum progesterone and immunoreactive human chorionic gonadotropin in normal early pregnancy. AB - The purpose of this study was to characterize the levels of progesterone and hCG and the variability of those levels over 24 h in early pregnancy. Venous blood sampling was performed every 30 min during the first trimester of a subsequently normal pregnancy in 19 women. The variability in each progesterone and hCG data series was evaluated by three methods: 1) comparing the coefficient of variation (CV) of each individual hormone data set to the respective assay CV, 2) examining each data set for pulses, and 3) relating changes in hormone levels to the ingestion of a meal. The CV for each individual progesterone data set was greater than the assay CV (CV progesterone, 3.7%) in all subjects (range, 5.58-21.90%). The CV for each individual hCG data set was greater than the assay CV for hCG (CV hCG, 4.3%) in 17 of 19 subjects (range, 3.27-10.95%). Mean (+/- SE) progesterone and hCG peak frequencies were 2.4 +/- 0.3 and 1.7 +/- 0.3/24 h, respectively. When postprandial levels of progesterone were normalized to a percentage of preprandial levels, there were maximum decreases in mean progesterone levels of 15.4 +/- 2.6% and 13.1 +/- 1.9% 1 h after initiation of the lunch and dinner meals, respectively (P less than 0.05). Postprandial hCG levels decreased by 2.3 +/- 1.9% and 0.4 +/- 1.6% during this same time period (P greater than 0.05). These findings suggest that 1) both progesterone and hCG levels fluctuate during a 24-h period in early pregnancy; 2) this variability of both hormones is greater than inherent assay variability and can be resolved into a short term pattern of pulses, suggesting alterations in episodic secretion, metabolic clearance, or volume of distribution of the hormone; and 3) a portion of the variability in the progesterone time set may be due to the ingestion of meals. PMID- 2199479 TI - Long term effect of incremental doses of the somatostatin analog SMS 201-995 in 58 acromegalic patients. French SMS 201-995 approximately equal to Acromegaly Study Group. AB - Fifty-eight acromegalic patients were included in a multicenter prospective study of increasing doses (300-1500 micrograms) of SMS 201-995 (octreotide, Sandostatin) administered 3 times daily, sc, during 6 months to determine its effect on signs and symptoms of GH hypersecretion. Subsequently, 34 of the patients were maintained for 12-26 months on the minimal efficacious dose, determined from the previous dose-response study. Some adverse effects were frequently encountered, mostly at the initiation of treatment, and disappeared with time. Asymptomatic gallstones occurred in 5 patients. Minimal changes in carbohydrate tolerance, consisting of a rise in blood glucose and a transient decrease in plasma insulin level after meals, were noted. GH normalized in 22% of the patients, improved in 56%, and remained unchanged in 22% regardless of the dose. The optimal daily dose was 300 micrograms in 50% of the patients and 1500 micrograms in 20%. Pituitary tumor size reduction occurred in 47% of the patients harboring large tumors or tumor remnants. No additional improvement or escape from being controlled occurred with time. These data indicate that SMS 201-995 is an effective treatment for refractory acromegaly and for some de novo patients for whom surgical therapy is not advisable. PMID- 2199480 TI - Presence and synthesis of inhibin subunits in human decidua. AB - A growing number of studies provided the evidence that human decidua is a pregnancy-related tissue capable of hormone production and metabolism. The aim of the present study was to evaluate the possible presence of inhibin subunits in human decidua. Tissue samples were collected in pregnant women during the first (8 weeks) and second trimester (18 weeks) of gestation and at term (40 weeks). Immunohistochemical data were obtained using affinity purified polyclonal antisera raised in rabbit against porcine alpha, beta A, or beta B subunits. Levels of the respective inhibin subunits were evaluated by Northern blot analysis using cDNA probes encoding sequences corresponding to each subunit. The present results indicated that human decidua contains and synthesizes inhibin alpha, beta A, and beta B subunits. The immunohistochemical data showed that decidual cells were stained with both inhibin alpha and beta B antisera, showing a similar localization. On the other hand, cells stained with inhibin beta A antisera were sparse and followed a distribution pattern different from that of cells stained with alpha or beta B antisera. The first inhibin alpha and beta B subunit mRNAs were both expressed in first trimester of pregnancy, and those mRNA levels showed a gestational related increase. The beta A subunit mRNA was expressed at very low levels at term and could not be detected earlier during pregnancy. The present data showed that human decidua actively produces inhibin subunits with a gestational-related profile. The results suggest that decidua may be a further source of inhibin-related proteins during pregnancy and emphasize the endocrine competence of human decidua. PMID- 2199481 TI - The Endocrine Society 1990 annual awards. PMID- 2199482 TI - Detection of Borrelia burgdorferi using the polymerase chain reaction. AB - Segments of the ospA gene of Borrelia burgdorferi were amplified by the polymerase chain reaction (PCR). Oligonucleotide primers used in the reaction flank a 309-base-pair segment within the ospA gene. After 35 cycles of amplification, the product could be detected by agarose gel electrophoresis or dot hybridization with a 32P-labeled probe. This segment was amplified in all strains of B. burgdorferi tested, but it was not detected in other bacterial species. An additional primer pair which has a broad specificity for conserved 16S rRNA sequences that are present in eubacteria amplified a 215-base-pair fragment in all organisms tested. The sensitivity of PCR for the detection of B. burgdorferi in clinical samples was evaluated by seeding blood and urine specimens with B. burgdorferi and subjecting them to amplification. We were able to detect 10 organisms per ml of blood or urine, using PCR with dot hybridization detection. DNA extraction is not required for sample preparation. Blood and urine specimens were obtained from canines with clinical and serologic evidence of Lyme disease and subjected to PCR analysis. Of 17 clinical specimens from 15 animals, one blood specimen showed reactivity in the PCR. PMID- 2199483 TI - Effect of endocervical specimen quality on detection of Chlamydia trachomatis and on the incidence of false-positive results with the Chlamydiazyme method. AB - Duplicate endocervical swabs were collected from 1,675 patients to assess the effects of variations in specimen quality on Chlamydiazyme (Abbott Laboratories) detection of Chlamydia trachomatis and the incidence of false-positive results. One swab (at random) from each patient was tested for C. trachomatis antigen by using the standard Chlamydiazyme procedure. A 200-microliter volume of 0.9% saline was added to the other swab from each patient. After vortexing, 20 microliters was smeared on a slide for Papanicolaou (Pap) staining and the remaining specimen was then tested with the Chlamydiazyme assay. The Chlamydiazyme result was positive for 170 (10.1%) and 165 (9.8%) of the stained and unstained duplicate specimens, respectively (no significant difference). Pap stains on smears from 1,536 (91.7%) of the patients were analyzed, and endocervical and/or metaplastic (E-M) cells were detected in 789 (51.4%) smears. Of these 1,536 stained and analyzed specimens, 150 (9.8%) were Chlamydiazyme positive but only 132 (88.0%) of the positive results were confirmed by repeating the test and using a monoclonal blocking antibody (Abbott). Confirmed Chlamydiazyme-positive results were obtained from only 34 (4.6%) of 747 specimens lacking E-M cells but from 98 (12.4%) of 789 specimens containing the cells (P less than 0.001). Of the 150 initially Chlamydiazyme-positive results obtained with Pap-stained, analyzed specimens, 12 (26.1%) of 46 were falsely positive from specimens lacking E-M cells but only 6 (5.8%) of 104 were falsely positive from specimens containing E-M cells (P less than 0.01). C. trachomatis antigen was detected significantly more frequently and false-positive results were significantly less common from specimens in which E-M cells were detected. PMID- 2199484 TI - Comparison of restriction endonuclease analysis and phenotypic typing methods for differentiation of Yersinia enterocolitica isolates. AB - Restriction endonuclease analysis of chromosomal DNA (REAC) was used to study polymorphism in restriction fragment patterns among Yersinia enterocolitica isolates belonging to serogroups O3, O5,27, O8, O9, O13, and O21. Using the enzyme HaeIII and electrophoresis on thin (0.75-mm) vertical 5% polyacrylamide gels, we were able to distinguish at least 22 DNA fragment patterns among the 72 strains examined. The method showed the greatest discriminatory power with regard to serogroup O8, within which as many as 10 different DNA fragment patterns were detected among the 16 strains examined. Compared with O8, serogroups O3 and O9 were relatively homogeneous with regard to REAC patterns. The discriminatory power of the method was compared with H-antigen typing, biotyping, phage typing, antimicrobial susceptibility typing, and restriction enzyme analysis of the virulence plasmid (REAP), by means of Simpson's index of diversity. The results showed that REAC and REAP constitute an effective supplement or alternative to conventional phenotypic methods for tracing epidemiologically related isolates of Y. enterocolitica. Our finding that human and porcine isolates exhibited the same REAC, REAP, and H-antigen patterns provides additional support for the hypothesis that pigs play an important role in the epidemiology of human Y. enterocolitica infection. PMID- 2199485 TI - Accuracy and reproducibility of the MicroScan rapid anaerobe identification system with an automated reader. AB - Rapid anaerobe identification (MicroScan) panels (4 h) were evaluated both visually and by the AutoScan-4, a computer-controlled microplate reader. The results of both reading methods were compared with identifications obtained by the conventional (Virginia Polytechnic Institute) method. In total, 237 anaerobes were tested. Correct identifications were obtained for 166 strains (70%) by visual reading and 157 strains (66.2%) by the AutoScan-4. Supplementary tests resulted in 80.1 and 76.7% total correct identifications, respectively. Comparison of the two reading methods revealed complete agreement for 169 strains. Differences between the two reading methods were due to difficulties in reading specific reactions. This was especially true with the clostridial species. The performance of the MicroScan system in the identification of anaerobic bacteria appears comparable to that of other 4-h identification systems for anaerobes, but this system shows significant variance from the conventional system. Improvements in the trays and data base are required before the system can be recommended for routine use. PMID- 2199486 TI - Serological evaluation of Escherichia coli-expressed human T-cell leukemia virus type I env, gag p24, and tax proteins. AB - Three proteins (env, gag, and tax) encoded by the human T-cell leukemia virus type I (HTLV-I) genome were cloned and expressed in Escherichia coli. The env protein contained a substantial part of the gp46 domain and a majority of the p21e domain. The gag protein contained all of p24 and portions of p19 and p15. In addition to these two structural proteins, a full-length tax (p40X) construct was obtained. All three recombinant proteins were purified to near homogeneity. When used in an immunoblot assay, the three recombinant proteins detected antibodies in more HTLV-I antibody-positive patient sera than did the corresponding native proteins. Antibodies to at least two of these three different gene products were detected in 98.4% of adult T-cell leukemia patients, 100% of HTLV-I-associated myelopathy patients, 97.4% of asymptomatic carriers, and 94% of uncharacterized HTLV-I-positive patients. Antibody to recombinant tax was found in 4.9% of adult T-cell leukemia patients, whereas antibody to recombinant env could not be detected. These recombinant proteins from three different gene products may be useful in detecting or confirming the presence of antibodies to HTLV-I. PMID- 2199487 TI - Specificity of bovine serum antibody to capsular carbohydrate antigens from Pasteurella haemolytica. AB - A more complete understanding of the bovine immune response to antigens of Pasteurella haemolytica biotype A, serotype 1, will improve control of bovine respiratory disease (BRD). Sera were obtained from blood samples of calves as they transited the market system of eastern Tennessee and were transported to a feedlot in Texas. The clinical histories and performance data were recorded and compared with serologic findings. The calves underwent a natural challenge of BRD. Serologic and bacteriologic evaluation indicated that P. haemolytica A1 was a significant component of the challenge. Serum antibody titers against P. haemolytica A1 capsular antigens (in enzyme-linked immunosorbent assay and hemolysin-in-gel test) increased by day 15 and continued at high levels through day 56. The animals that remained free of BRD had higher initial serum antibody concentrations than those that succumbed to BRD. The specificity of the immunoglobulin G subclass 1 (IgG1) anticapsular antibody to P. haemolytica A1 increased from day 8 to day 29 as evidenced by a decrease in P. haemolytica A2 absorption inhibition from 60% (day 8) to 15% (day 29). However, IgA, IgG2, and IgM were more serotype specific on both days 8 and 29. There were no significant changes in anti-P. haemolytica A2 antibody titers. Both in vitro complement dependent bacteriolysis and C3 deposition on the surface of the bacteria increased significantly (P less than 0.01) in a serotype-specific fashion from day 8 to day 29. These calves showed a humoral immune response to capsular polysaccharide antigens of P. haemolytica A1. Such a response may be an important component of immunity to BRD. PMID- 2199488 TI - Rapid detection of respiratory syncytial virus and influenza A virus in cell cultures by immunoperoxidase staining with monoclonal antibodies. AB - Peroxidase-labeled monoclonal antibodies against respiratory syncytial virus (RSV) and influenza A virus were used for immunoperoxidase staining (IPS) of cell cultures inoculated with nasopharyngeal aspirates. Cells were grown in 24-well plates, and specimens were inoculated by low-speed centrifugation. Cultures were incubated for 2 days at 37 degrees C and then fixed, stained, and observed by light microscopy. IPS was compared with standard virus isolation by using cultures of human diploid fibroblasts and Vero, HEp-2, and HeLa cell lines for RSV and Madin-Darby canine kidney cells for influenza A virus; these cultures were inoculated with specimens that were previously stored at -70 degrees C. Of 40 known RSV-positive specimens, 30 were found to be positive on reinoculation by both methods, and an additional 5 specimens were found to be positive by IPS only. Of 190 specimens tested for influenza A virus, 14 were positive by IPS and in tubes, and a further 8 specimens were positive by IPS only. IPS was also compared with direct detection of viral antigens in nasopharyngeal aspirates by a time-resolved fluoroimmunoassay (TR-FIA). Fresh nasopharyngeal aspirates were inoculated into human diploid fibroblasts and Madin-Darby canine kidney cells and tested for RSV and influenza A virus, respectively, by IPS. Of 110 specimens tested for RSV, 37 were positive in total, 32 were positive by IPS, and 33 were positive by TR-FIA. Of 150 specimens tested for influenza A virus, 39 were positive in total, 35 were positive by IPS, and 34 were positive by TR-FIA. IPS of cultures inoculated by centrifugation and incubated for 2 days is a sensitive method for the diagnosis of respiratory virus infections, and 24-well plates allow for the easy processing of a large number of specimens. PMID- 2199489 TI - Use of two-dimensional gas chromatography with electron-capture detection for the measurement of lipopolysaccharides in peritoneal fluid and plasma from rats with induced peritonitis. AB - The content of 3-hydroxymyristic acid from Escherichia coli lipopolysaccharide in peritoneal fluid and plasma from rats was determined by two-dimensional gas chromatography with electron-capture detection of the 3-O-pentafluorobenzoyl methyl ester derivative. The detection limit of lipopolysaccharide in peritoneal fluid was 3 ng/ml. An experimental model of E. coli peritonitis in the rat was used, with and without coinjection of bile. The concentrations of lipopolysaccharide were highest in both peritoneal fluid and plasma samples from rats injected with E. coli and bile, reaching a maximum 1 h after injection by the gas chromatographic method. Corresponding Limulus assay results for peritoneal samples showed a small increase of lipopolysaccharide concentrations during the first 4 h after injection, followed by a substantial increase. The results indicate that bile salts cause an increased release of lipopolysaccharide from gram-negative bacterial cells in vivo and that this may be responsible for the high mortality caused by peritonitis. In contrast to the Limulus assay, gas chromatography enables the total amount of lipopolysaccharide in a clinical sample to be determined. PMID- 2199490 TI - Evaluation of a human immunodeficiency virus test algorithm utilizing a recombinant protein enzyme immunoassay. AB - Many truly human immunodeficiency virus (HIV) antibody-negative serum samples may be unnecessarily subjected to costly and time-consuming Western blots (immunoblots). An investigation was undertaken to evaluate the efficiency of using a recombinant protein-based enzyme immunosorbent assay (EIA; Cambridge BioScience [CBC] Recombigen HIV EIA) as an adjunct to whole viral lysate EIA. A total of 2,212 serum samples which had been screened by viral lysate EIA were tested by CBC EIA in parallel with the Western blot. The sensitivity and specificity of the CBC kit were 99.9 and 99.7%, respectively. Positive and negative predictive values were 99.7 and 99.9%, respectively. The high sensitivity of this kit and its high negative predictive value make it an attractive addition to an HIV testing algorithm by reducing the number of Western blot tests on truly antibody negative serum samples. PMID- 2199491 TI - Antibody-independent inhibition of Plasmodium falciparum in vitro cultures. AB - The sera of 100 Colombian individuals of African origin living in a malaria endemic area of the Pacific coast were studied with regard to their capacity to inhibit Plasmodium falciparum cultures in vitro. Antimalarial antibody levels determined by indirect immunofluorescence were higher in the group of infected individuals than in the noninfected individuals, and inhibitory activity assessed by the inhibition of parasite incorporation of 3H-hypoxanthine in vitro was present in the sera of both the infected and noninfected patients. We believe that the noninfected patients were probably immune. The sera of some of the infected patients had high inhibitory capacities for the P. falciparum FCB-1 isolate. When the inhibitory effects of some of the sera were tested by using four parasite isolates from different regions of the world, striking differences among them were found. PMID- 2199492 TI - Proposal of a new serovar and altered nomenclature for Haemophilus paragallinarum in the Kume hemagglutinin scheme. AB - By using the Kume hemagglutinin serotyping scheme, 13 Australian isolates of Haemophilus paragallinarum were shown to constitute a new serovar within the presently termed serogroup II. Because of the likelihood that new serovars will continue to be established, we propose a rationalization of the nomenclature of the Kume scheme. Under this altered scheme, the three recognized serogroups I, II, and III are renamed A, C, and B, respectively. Within each of the serogroups, the serovars are numbered sequentially, allowing new serovars to be added in numerical order. Thus, the nine currently recognized Kume serovars are termed A 1, A-2, A-3, A-4, B-1, C-1, C-2, C-3, and C-4. PMID- 2199493 TI - Computer-assisted methods for assessing strain relatedness in Candida albicans by fingerprinting with the moderately repetitive sequence Ca3. AB - When used to probe EcoRI-digested Candida albicans DNA, the moderately repetitive sequence Ca3 generated a Southern blot hybridization pattern which included 15 to 25 bands, depending upon the strain. The pattern was stable through 400 generations in each of three independent strains but variable between most of 46 unrelated tester strains, making it a very effective probe for discrimination between strains. Computer-assisted methods (Dendron) were developed for storage of Ca3 patterns in data files, calculation of similarity (SAB) values between strains based upon band positions and intensities, and generation of histograms and dendrograms based on SAB values for all strains or any subset of strains in large epidemiological studies. In testing the effectiveness of the system, it was found that (i) multiple isolates from different body locations of the same healthy individual could represent either the same strain or different strains, (ii) isolates from oral lesions of a husband and wife represented the same strain, (iii) strains isolated from the mouths of 10 healthy individuals on the same day and in the same geographical location were as dissimilar on average as the 46 unrelated tester strains, and (iv) strains isolated from seven immunocompromised patients hospitalized over a 2.5-month period in the same hospital were highly similar, indicating nosocomial origin. The apparent effectiveness of these fingerprinting methods and the Dendron program suggests that interlaboratory procedures for fingerprinting should be standardized and all patterns should be analyzed and stored in a common and accessible data base for broad epidemiological analysis. PMID- 2199494 TI - Enzyme-linked immunosorbent assay for immunoglobulin M specific antibody for the diagnosis of melioidosis. AB - Indirect hemagglutination (IHA) is commonly used for serodiagnosis of melioidosis. However, in endemic areas, high background titers in normal populations and occasional low titers in patients with septicemic melioidosis prompted a search for a more sensitive and more specific method of serodiagnosis. An indirect fluorescent-antibody test for immunoglobulin M (IgM) specific antibody to Pseudomonas pseudomallei was more sensitive and more specific, but fluorescence microscopes are rarely available in the endemic areas. An enzyme linked immunosorbent assay (ELISA) for IgM antibody is an attractive alternative. An indirect ELISA for IgM antibody (IgM ELISA) and an IgM antibody capture ELISA for melioidosis were developed. Both tests, together with IHA, were evaluated for 153 serum specimens from blood donors and 16 serum specimens from 16 melioidosis patients. It was found that IHA, the IgM ELISA, and the IgM antibody capture ELISA had sensitivities of 88, 88, and 75%, respectively, with specificities of 97.4, 92.2, and 91.5%, respectively. When IHA was combined with IgM ELISA, a sensitivity of 100% and a specificity of 95.4% were obtained. The IgM ELISA and IHA should be used in combination for serodiagnosis of melioidosis. PMID- 2199495 TI - Use of polymerase chain reaction for detection of Chlamydia trachomatis. AB - A polymerase chain reaction (PCR) assay was developed for detection of Chlamydia trachomatis DNA. From the published sequence of the common C. trachomatis plasmid, two primer sets were selected. Detection of amplified sequences was done by agarose gel electrophoresis of cleaved or uncleaved amplified sequences, Southern hybridization, or dot blot analysis. The PCR assay was optimized and, after 40 cycles of amplification with primer set II, demonstrated a sensitivity of 10(-17) g of DNA, which corresponds to the detection of one copy of the plasmid. Because of the high sensitivity, we developed a closed system in which airborne contamination was minimized. Analysis of 228 clinical samples tested by cell culture, IDEIA enzyme immunosorbent assay (Medico-Nobel, Boots-Celltech Ltd., Berkshire, United Kingdom), and PCR showed a sensitivity of 100%, a specificity of 93% when PCR was compared with cell culture, and a corrected specificity of 99% when PCR was compared with cell culture or IDEIA. PMID- 2199496 TI - Isolation and identification of autoagglutinating serogroup O:11 Aeromonas strains in the clinical laboratory. AB - We evaluated the extent to which serogroup O:11 Aeromonas strains could be recovered from both clinical and environmental specimens and the cultural parameters that affected the phenotypic marker (autoagglutination) associated with this group. Of over 200 Aeromonas strains screened, serogroup O:11 was identified only among the phenospecies A. hydrophila and A. sobria and was associated with clinical isolates more frequently than with environmental strains. Blood and wound isolates accounted for almost 50% of all O:11 strains identified. The autoagglutination phenotype associated with O:11 strains could be detected in most commercial liquid media, under a wide range of growth temperatures, and within 15 min of incubation at 100 degrees C. The results suggest that clinical laboratories can recognize this important group of Aeromonas strains by two simple tests. PMID- 2199497 TI - Isolation, characterization, and host-cell-binding properties of a cytotoxin from Campylobacter jejuni. AB - A 68,000-molecular-weight protein was isolated by polyacrylamide gel electrophoresis from the organism-free filtrate of a fully virulent clinical strain of Campylobacter jejuni. The eluted protein was heat labile, was inactivated at either pH 3.0 or 9.0, was sensitive to trypsin, and was lethal for fertile chicken eggs. It also had toxic effects on chicken embryo fibroblast, Chinese hamster ovary (CHO), and intestinal 407 (Int407) cells. A monoclonal antibody (CETPMAb4) raised to this eluted toxic protein (ETP) from C. jejuni abolished these toxic activities. Homology between C. jejuni ETP and Vibrio cholerae toxin was not observed in that specific antisera to each did not block their respective toxic activities. In enzyme-linked immunosorbent assays, ETP, unlike chlorea enterotoxin, did not bind to GM1 ganglioside. Furthermore, the C. jejuni toxin had cytotoxinlike properties and induced rounding of CHO cells. Binding of ETP to Int407 and primary chicken embryo fibroblast cells was maximal after 2 h as assessed by enzyme-linked immunosorbent assay, and this toxin adherence to host cell membranes was significantly reduced by prior treatment of the cells with proteolytic enzymes, neuraminidase, or glutaraldehyde but not by treatment with beta-galactosidase, lipase, Nonidet P-40, or sodium metaperiodate. In competitive binding assays, sugars, lectins, or GM1 ganglioside did not adversely influence uptake of ETP by these cells. These results suggest that the ETP produced by C. jejuni is a cytotoxin which binds to Int407 cells via a protein- or glycoproteinlike receptor on cell membranes and possesses properties dissimilar to those of V. cholerae toxin. PMID- 2199498 TI - Epidemiological markers for epidemic strain and carrier isolates in an outbreak of nosocomial oxacillin-resistant Staphylococcus aureus. AB - An outbreak of nosocomial infections occurring in a postoperative intensive care unit was caused by a single strain of oxacillin-resistant Staphylococcus aureus. Six patients were infected, or colonized, by this strain, which was traced by using the following four epidemiological markers: antibiogram, bacteriophage type, capsular polysaccharide type, and esterase electrophoretic type. This strain was compared with S. aureus isolates obtained from the noses of 13 carriers from a group of 42 staff members. A good correlation in terms of phenotypic markers was found between the epidemic strain and a strain isolated from one carrier. Both exhibited the same pattern of multiple resistance as well as the same phage type, 77, capsular polysaccharide type, 5, and esterase electrophoretic type, 6. In contrast, an oxacillin-resistant strain, isolated from another carrier, differed from the epidemic strain by susceptibility to rifampin and by susceptibility to four additional bacteriophages. The other 11 strains isolated from carriers were susceptible to oxacillin and exhibited widely different phenotypes. These results confirm the interest of using several epidemiological markers to trace the spread of epidemic S. aureus strains and to delineate the carrier strains. PMID- 2199499 TI - Characterization of a tick isolate of Borrelia burgdorferi that possesses a major low-molecular-weight surface protein. AB - An unusual strain of Borrelia burgdorferi (DN 127 cl 9-2) that was isolated from an Ixodes pacificus tick did not react with monoclonal antibodies (MAbs) to OspA and OspB surface proteins, which are found in most U.S. strains. The strain exhibited an abundant protein with an apparent molecular weight of 25,000 (25K protein). A MAb, 86 DN-1, that was prepared to the 25K protein was used in studies on the effect of proteases on the intact spirochetes, immune electron microscopy, and Western blot (immunoblot) analyses; the results indicated that the low-molecular-weight protein was an apparent surface protein that was loosely attached to the spirochete. Five tick isolates from California possessed low molecular-weight proteins in the 20,000- to 25,000-molecular-weight range that reacted with the 86 DN-1 MAb. The 25K protein of DN 127 cl 9-2 was unaffected by prolonged in vitro passage of cultures in BSK II medium, while the low-molecular weight proteins of the other strains of B. burgdorferi from California either decreased in quantity or became undetectable on long-term in vitro passage. PMID- 2199500 TI - Detection of respiratory syncytial virus antigen in nasal washings by Abbott TestPack enzyme immunoassay. AB - We compared the new Abbott TestPack (TP) respiratory syncytial virus (RSV) enzyme immunoassay (EIA) with cell culture and two commercial RSV EIAs (from Abbott Diagnostics and Kallestad Laboratories) by using split samples of fresh nasal washings from children with suspected RSV disease. Two tubes of HEp-2 cells were inoculated and observed for cytopathic effect for 14 days, and isolates were confirmed by immunofluorescence. The TP EIA was performed by following the manufacturer's instructions. Specimens positive by TP EIA but negative by culture were examined in a competitive inhibition (blocking) assay using the TP EIA, and rabbit anti-RSV serum. Of 218 specimens, 93 were positive by culture, 105 were positive by TP EIA, 80 were positive by the Abbott Diagnostics EIA, and 87 were positive by the Kallestad Laboratories EIA. The sensitivity, specificity, positive predictive value, and negative predictive value of the TP EIA were 92, 86, 81, and 93%, respectively. Of 20 apparently false-positive TP EIAs, 10 of 14 that were positive when retested were neutralized in the blocking assay, indicating that they were truly positive. The recalculated sensitivity, specificity, positive predictive value, and negative predictive value of the TP EIA were 92, 91, 90, and 93%, respectively. We conclude that the TP EIA is easy to perform, rapid (less than 0.5 h), and accurate. PMID- 2199501 TI - Detection of hepatitis B virus DNA in serum by polymerase chain reaction amplification and microtiter sandwich hybridization. AB - We have developed a microtiter sandwich hybridization assay for the detection of polymerase chain reaction (PCR)-amplified hepatitis B virus (HBV) sequences. This assay utilizes an enzyme-linked immunosorbent assay-like format in which cloned DNA containing a sequence complementary to half of one PCR product strand is immobilized in microtiter wells. A biotin-labeled DNA sequence complementary to the other portion of the same PCR product strand is used as the probe. The DNAs from 69 hepatitis B surface antigen-positive serum samples and 16 antigen negative control samples were amplified by the PCR procedure, and the product was detected by Southern and sandwich hybridization. Both detection procedures were capable of detecting as few as five copies of HBV DNA. Compared with Southern hybridization, the sandwich hybridization assay exhibited a sensitivity of 100% and a specificity of 95% for the detection of amplified HBV sequences. Unlike Southern hybridization, however, the sandwich hybridization assay employs a nonradioactive probe and allows easy handling of large numbers of samples. DNA was detected in 74% of the antigen-positive samples. All of the antigen-negative samples (healthy blood donors) were negative for HBV DNA by both procedures. PMID- 2199502 TI - Detection and characterization of fecal verotoxin-producing Escherichia coli from healthy cattle. AB - Verotoxin-producing Escherichia coli isolates from feces of healthy cattle were identified by DNA hybridization with verotoxin 1- and verotoxin 2-specific gene probes. Among 259 animals investigated, 28 (10.8%) were found to carry verotoxin producing E. coli strains. Characterization of the verotoxin-producing isolates revealed a heterogeneous population in terms of serotype and toxin type. Nearly 40% of the strains belonged to serogroups known to be pathogenic for humans, i.e., O22, O39, O82, O91, O113, O116, O126, and O136. Two isolates from different bulls were identified as serotype O157:H7. Results obtained in this study indicate that cattle may be an important source of verotoxigenic E. coli involved in human disease. PMID- 2199503 TI - Evaluation of a new bicolored latex agglutination test for immunological diagnosis of hepatic amoebiasis. AB - A new bicolored latex agglutination amoeba test (BLA) for detection of antibodies against Entamoeba histolytica was evaluated for its practicability and diagnostic sensitivity and specificity. BLA is rapid (5 min) and simple to perform. It requires only 20 microliters of a 1/3-diluted serum, 17 microliters of reagent, and a glass slide. Reading of the test is easy because a positive result shows a green spot with a red surrounding edge. This bicolored pattern is easily distinguishable from the negative test result, which shows a homogeneous dark brown spot. By using serum samples from 348 individuals, BLA was compared with immunofluorescence assay, indirect hemagglutination, and counterimmunoelectrophoresis. Sensitivity, specificity, efficiency, and positive and negative predictive values of the four methods were almost identical. The results of this study indicate that BLA could be very useful both as a screening method for the diagnosis of invasive amoebiasis and for epidemiological purposes. PMID- 2199504 TI - Comparison of three enzyme immunoassays to tissue culture for the diagnosis of rotavirus gastroenteritis in infants and young children. AB - Three enzyme immunoassays (EIAs), Rotazyme II, IDL, and Pathfinder, were evaluated for rotavirus detection in stool and rectal swab specimens from children with symptomatic gastroenteritis and compared with virus isolation in primary African green monkey kidney cells. Of 125 specimens tested, 49 were rotavirus positive by tissue culture isolation; of these 49, 40 were positive by Rotazyme II, 43 were positive by IDL, and 46 were positive by Pathfinder EIAs. As compared with tissue culture isolation, the Rotazyme II, IDL, and Pathfinder EIAs had sensitivities of 82, 88, and 94%, specificities of 90, 99, and 95%, and overall agreements of 86, 94, and 94%, respectively. PMID- 2199505 TI - Sialidase activity of the "Streptococcus milleri group" and other viridans group streptococci. AB - Viridans group streptococci were examined for the production of sialidase (neuraminidase) activity, using the fluorescent substrate 4-methylumbelliferyl alpha-D-N-acetylneuraminic acid in a simple and rapid (15-min) assay. Sialidase was produced by all strains of Streptococcus oralis and S. intermedius and by a majority of S. mitis strains. S. mutans, S. sobrinus, S. gordonii, S. sanguis, S. vestibularis, S. salivarius, S. anginosus, S. constellatus, "S. parasanguis," and the "tufted fibril group" were uniformly negative. Sialidase production may be a useful characteristic to assist in the identification of viridans group streptococci. PMID- 2199506 TI - Comparison of Kodak Surecell Chlamydia Test Kit with culture for the diagnosis of chlamydial conjunctivitis in infants. AB - The accuracy of the Surecell Chlamydia Test Kit (Kodak Clinical Products, Rochester, N.Y.) in detecting neonatal conjunctival infection caused by Chlamydia trachomatis was determined by comparison of this enzyme immunoassay with the isolation of C. trachomatis in tissue culture. Kodak Surecell is a rapid monoclonal antibody-based membrane capture enzyme immunoassay which can be processed in the office of a physician. The sensitivity and specificity compared to culture in detecting C. trachomatis in conjunctival specimens from infants with conjunctivitis were 93 and 96%, respectively. The test does not require specialized equipment or trained personnel and would be ideal for physicians who see low numbers of infants with possible chlamydial conjunctivitis in their offices. PMID- 2199507 TI - Identification of Yersinia species by the API 20E. AB - A prospective study was performed to assess the effectiveness of the API 20E in the identification of 183 Yersinia isolates incubated at 28 degrees C for 18 to 24 h. The results showed an overall correct-identification rate of 90%, with positive predictive values for Yersinia enterocolitica and Yersinia frederiksenii of 94 and 92%, respectively. Yersinia intermedia results were unacceptable. PMID- 2199509 TI - Evaluation of the LOGIC system for the rapid identification of members of the family Enterobacteriaceae in the clinical microbiology laboratory. AB - The LOGIC identification system (J.D. Perry, M. Ford, N. Hjersing, and F.K. Gould, J. Clin. Pathol. 41: 1010-1012, 1988) for gram-negative rods, performed with microdilution plates instead of tubes, was evaluated for strains isolated from all tested specimens except those obtained from stools (for which a different strategy was followed). Systematically extended with the oxidase test and lactose fermentation, it proved to be very reliable and extremely simple and economical. PMID- 2199508 TI - Comparison of IDEIA III and cell culture for the detection of Chlamydia trachomatis in endocervical specimens. AB - A total of 803 endocervical samples were obtained from females with clinical or epidemiological histories suggesting chlamydia infection. These specimens were tested by IDEIA III and cell culture for the presence of Chlamydia trachomatis. After resolution of discrepant results by direct fluorescent-antibody staining of pelleted cell culture transport materials, IDEIA III demonstrated sensitivity, specificity, and positive and negative predictive values of 93.8, 99, 92.9, and 99.1%, respectively. PMID- 2199510 TI - Evaluation of the Becton Dickinson Directigen test for respiratory syncytial virus in nasopharyngeal aspirates. AB - A premarket trial of the Becton Dickinson Directigen respiratory syncytial virus membrane-based enzyme immunoassay compared the test with virus isolation for the detection of respiratory syncytial virus in 583 nasopharyngeal aspirates. After modification, the Directigen test showed a sensitivity of 83% and a specificity of 90%. It offers the potential for an efficient bedside test--without the need for any equipment--for the diagnosis of respiratory syncytial virus infection and requires only a 0.25-ml sample volume. However, for optimum reliability, freezing thawing of samples and access to a confirmatory test were shown to be necessary. PMID- 2199511 TI - Production of Shiga-like toxin among Escherichia coli strains and other bacteria isolated from diarrhea in Sao Paulo, Brazil. AB - An elevated level of Shiga-like toxin I (SLT-I) production was found in 1 of 466 Escherichia coli strains studied. Among the 34 sonic lysates obtained from classical enteropathogenic E. coli, 5 produced SLT-I. The Aeromonas, Citrobacter, Edwardsiella, Enterobacter, Klebsiella, Proteus, Providencia, Pseudomonas, Salmonella, Serratia, Shigella, Yersinia, and Vibrio strains also studied were not SLT producers, except for a Shigella dysenteriae type 1 strain. Although SLT I-producing E. coli strains were isolated from diarrhea, they seem to be an uncommon cause of disease in children less than 1 year old in our community. PMID- 2199512 TI - Liposome immunoassay for rapid identification of group A streptococci directly from throat swabs. AB - The Q Test Strep (Becton Dickinson and Co., Franklin Lakes, N.J.) is a new solid phase liposome immunoassay for the rapid diagnosis of group A beta-hemolytic streptococcal pharyngitis. Compared with blood agar plate cultures, the Q Test Strep had a sensitivity of 91%, a specificity of 83%, a positive predictive value of 88%, and a negative predictive value of 87%. Liposome technology can be used to facilitate the rapid diagnosis of group A beta-hemolytic streptococcal pharyngitis. PMID- 2199513 TI - Identification of enterotoxigenic Escherichia coli by colony hybridization with nonradioactive digoxigenin-labeled DNA probes. AB - Enterotoxigenic Escherichia coli (ETEC) strains were readily identified in pure and mixed cultures with nonradioactive, digoxigenin-labeled DNA probes coding for heat-labile (LTI) and heat-stable (STaI, STaII, and STb) enterotoxins. Digoxigenin-labeled ETEC fragments were more sensitive than and exhibited less nonspecific background contamination than biotinylated ETEC probes. PMID- 2199514 TI - Evaluation of the indoxyl acetate hydrolysis test for the differentiation of Campylobacters. AB - Indoxyl acetate hydrolysis is a rapid, inexpensive differential test which can be performed easily to help identify campylobacter. A total of 571 Campylobacter cultures, including atypical variants, representing 10 species was tested. PMID- 2199515 TI - Discriminant analysis of cellular fatty acids of Candida species, Torulopsis glabrata, and Cryptococcus neoformans determined by gas-liquid chromatography. AB - We used discriminant analysis of cellular fatty acid compositions determined by gas-liquid chromatography to differentiate yeastlike fungi (a total of 190 strains; including 37 Candida albicans strains, 21 Candida krusei strains, 13 Candida guilliermondii strains, 37 Candida tropicalis strains, 10 Candida pseudotropicalis strains, 24 Candida parapsilosis strains, 32 Torulopsis glabrata strains, and 16 Cryptococcus neoformans strains). Previous results with a standard strain of C. albicans indicated that reproducible fatty acid chromatograms can be obtained with cells grown in a medium of 2% Sabouraud glucose agar at 35 degrees C for between 48 and 72 h. These conditions were also maintained in cultures of the other organisms that we studied. The cellular fatty acid compositions of the organisms were determined quantitatively by gas-liquid chromatography and analyzed by discriminant analysis. The total correct identification expressed as relative peak percent was 95.8% (89.2% for C. albicans to 100% for C. krusei, C. guilliermondii, C. pseudotropicalis, T. glabrata, and C. neoformans). The total correct identification expressed as the common peak (palmitic acid) ratio was 94.7% (87.5% for C. parapsilosis to 100% for C. pseudotropicalis, T. glabrata, and C. neoformans). Both results suggest that cellular fatty acid compositions can be differentiated by this method. PMID- 2199516 TI - Evaluation of the ATB 32 A system for identification of anaerobic bacteria isolated from clinical specimens. AB - A new miniaturized 4-h method for the identification of anaerobic bacteria, ATB 32 A (API System SA, Montalieu Vercieu, France), was evaluated against conventional methods of identification. The evaluation was done by using 260 recent clinical isolates and 21 reference strains of anaerobic bacteria. All reference strains were correctly identified and did not figure in the detailed analysis. Of the 140 gram-negative bacilli, 90.6% of Bacteroides spp. and 95.5% of Fusobacterium spp. were correctly identified to the species level, with an additional 8.4% of the Bacteroides spp. being identified to the genus level. Clostridia were correctly identified in 85.9% of cases, with an additional 9.9% being identified to the genus level. Peptostreptococci were correctly identified in 91.6% of cases. The 4 strains of Actinomyces spp. were all identified correctly, as were 10 of the 11 strains of Propionibacterium spp. A total of 3.1% of strains were not identified by ATB 32 A, while for 1.9% of strains, completely false identifications were obtained. Estimation of the individual preformed enzyme results may pose problems, although these decrease with familiarity with the system. With certain enzyme profiles, additional testing was necessary to arrive at an identification; however, there was no requirement for gas-liquid chromatography. If certain additions are made to the data base and the difficulties of determination of organisms to the species level among the non Bacteroides fragilis (sensu stricto) members of the B. fragilis group can be reduced, this system holds promise as a reliable standardized alternative for the identification of anaerobic bacteria in clinical laboratories. PMID- 2199517 TI - Evaluation of Syva enzyme immunoassay for detection of Chlamydia trachomatis in genital specimens. AB - Detection of Chlamydia trachomatis infection was evaluated by culture and a new Syva enzyme immunoassay (EIA) in 1,012 patients at two Baltimore, Md., sexually transmitted disease clinics. The overall chlamydia prevalence determined by culture was 12%. For 506 fresh cervical and urethral specimens, the sensitivity of Syva EIA was 90% and its specificity was 94% compared with culture. Discordant Syva EIA results were further evaluated by staining the sediment in centrifuged culture transport media and Syva EIA transport tubes with a fluorescent monoclonal antibody to C. trachomatis to detect elementary bodies. Reanalysis of the data after use of this technique to resolve discordant results increased sensitivity and specificity to 92 and 96%, respectively. A subsample of 307 fresh cervical specimens was also tested in a three-way comparison using Abbott Chlamydiazyme, Syva EIA, and culture. In this sample, compared with culture, the sensitivity and specificity of Syva EIA were 87 and 95%, respectively, and for Chlamydiazyme they were 77 and 98%, respectively. Syva EIA is a 4-h, easy-to perform enzyme-linked immunosorbent assay which has a high sensitivity with fresh genital specimens and offers an excellent alternative to culture. PMID- 2199519 TI - Use of immunoblotting to detect Aspergillus fumigatus antigen in sera and urines of rats with experimental invasive aspergillosis. AB - Immunoblotting was used to detect Aspergillus fumigatus antigen in sera and urines of immunosuppressed rats experimentally infected with A. fumigatus. Organisms were administered by both intravenous and intratracheal injections. Intravenously infected rats developed disseminated aspergillosis, but intratracheally infected rats developed pulmonary disease only. Fungal cultures of blood and urine samples from infected rats were negative. In the urines of intravenously infected rats, antigen was detected 24 to 48 h after infection; in the urines of intratracheally infected animals, antigen was detected on days 4 to 5 after infection. Antigen in serum was detected later than antigen in urine was. Following sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting of serum and urine samples, the most strongly reacting antigenic materials were found in the 88-, 40-, 27-, and 20-kilodalton regions. These dominant antigens appeared to be the same as those of control antigens prepared from A. fumigatus grown in vitro. Rabbit antiserum to Aspergillus filtrate antigen was found to be more immunoreactive than antiserum to mycelial or conidial antigen. No mycelium-specific antigens were detected. PMID- 2199518 TI - Longitudinal survey in an endemic region of plasma soluble interleukin-2 receptor and antibody levels in Plasmodium falciparum malaria. AB - A survey involving 81 individuals living in Dafinso and Vallee du Kou no. 4 (near Bobo-Dioulasso), Burkina Faso, was performed in June 1987, August to September 1987, and January 1988, respectively, at the beginning of, during, and after the transmission season of malaria. The clinical longitudinal study during the transmission period allowed us to define three different groups in terms of both age and occurrence of malaria attack (5,000 Plasmodium falciparum per mm3 of blood and axillary fever of greater than 37.7 degrees C) as follows: group 1, persons less than or equal to 15 years old who had at least one malaria attack during the transmission period; group 2, individuals less than or equal to 15 years old who did not have any malaria attacks; and group 3, individuals considered to be protected (adults greater than 15 years old with no malaria attacks). Soluble interleukin-2 receptor (sIL-2R) levels were found to be significantly increased (P less than 0.001) in the first two groups (1,047 +/- 481 U/ml [mean +/- standard deviation]) as compared with the adult group (605 +/- 307 U/ml). Considering all the groups, no significant difference was observed between observation periods. Levels of sIL-2R were inversely correlated (r = 0.39, n = 237, P less than 0.01) with age (range, 4 to 67 years). Negative correlations were also noticed between the levels of sIL-2R and those of antibodies to somatic antigen of P. falciparum (immunoglobulin G [IgG] class [r = -0.33, n = 237, P less than 0.01] and IgM class [r = -0.20, n = 237, P less than 0.05]). IgG antibody levels to somatic antigen were correlated with age, but IgM antibody levels to somatic antigen were not. The possible role played by sIL-2R in effector mechanisms against malaria is discussed. PMID- 2199520 TI - Accuracy of Chlamydia trachomatis antigen detection methods in a low-prevalence population in a primary care setting. AB - We compared a direct fluorescent-antibody stain (DFA) and an enzyme immunoassay (EIA) with a standard cell culture technique for the detection of Chlamydia trachomatis infection in women in an urban family practice setting. We also evaluated a DFA sample in a commercial laboratory to determine the interlaboratory reliability of this test. There were 268 women in the study; the EIA provided a higher sensitivity (83 versus 50%) and a higher positive predictive value (83 versus 69%) than the DFA test and comparably high specificity (99 versus 98%). Concordance between the two laboratories on the DFA test was not high when data were adjusted for chance agreement (kappa coefficient = 0.64). DFA validity was optimal with an elementary body cutoff of greater than 5, while EIA validity was optimal at the recommended cutoff of 0.1 optical density unit. None of 11 women with negative cultures after treatment had false positive antigen tests. False-negative results with both tests were associated with low culture inclusion counts but were not strongly associated with the presence or absence of symptoms, menses, pregnancy, or recent antibiotic use. False-positive results with EIA were seen only for three women who had a chief complaint of vaginal discharge. Although the positive predictive value of DFA could be increased in high-prevalence subpopulations, EIA was still more valid in two such groups: teenagers and prenatal patients. These results indicate that EIA might be preferable for low- or moderate-prevalence populations in primary care settings and that a falloff in DFA sensitivity could be explained by lower infection burdens in low-prevalence groups. PMID- 2199522 TI - Evaluation of autoSCAN-W/A automated microbiology system for the identification of non-glucose-fermenting gram-negative bacilli. AB - We evaluated the ability of the autoSCAN-W/A (MicroScan Division, Baxter Healthcare Corporation, West Sacramento, Calif.), in conjunction with the dried colorimetric Neg ID type 2 panel (DCP) and new rapid fluorometric Neg ID panel (RFP), to identify non-glucose-fermenting gram-negative bacilli by challenging the system with 310 previously identified reference strains. Of these 310 isolates, 286 organisms were in the DCP data base and 269 were in the RFP data base. Use of the DCP panels resulted in 118 (41.3%) correct and 64 (22.4%) incorrect first choice identifications at greater than or equal to 85% probability, 61 (21.3%) low-probability identifications, and 43 (15.0%) reports of unidentified organisms. The RFP system reported 135 (50.1%) correct and 25 (9.3%) incorrect identifications at greater than or equal to 85% probability and 109 (40.5%) low-probability identifications. Unidentified isolates (DCP system only) and isolates producing low-probability first choice identifications (both systems) required supplementary biochemical testing. Over half (37 of 64 [57.8%]) of the DCP misidentifications were due to four commonly isolated, saccharolytic organisms (Alcaligenes xylosoxidans subsp. xylosoxidans, Pseudomonas putida, Pseudomonas fluorescens, and Xanthomonas maltophilia), while 7 of 25 (28%) of misidentifications in the RFP system were due to P. fluorescens. Of note, the RFP system identified non-glucose-fermenting gram-negative bacilli within 2 h of panel inoculation, allowing additional conventional biochemical tests to be set up the same day on low-probability isolates, whereas only 13.5% of the DCPs could be read at 18 h, with the remainder requiring 42 h of incubation before reading. When organism identifications were recalculated with the updated RFP data base and revised software, only 8.1% of all 310 isolates were misidentified at greater than or equal to 85% probability while 77.1% of the isolates were now correctly reported at this same high probability. PMID- 2199521 TI - A new attempt to distinguish serologically the subspecies of Treponema pallidum causing syphilis and yaws. AB - In an effort to serologically differentiate syphilis from yaws, 69 monoclonal antibody species raised against Treponema pallidum subsp. pallidum were tested by immunoblotting for their reactivity with Treponema pallidum subsp. pertenue. All monoclonal antibodies reacted with antigens with the same molecular weight of both subspecies. Furthermore, no differences in reactivity between sera from yaws patients and from syphilis patients were found by Western blot (immunoblot) analysis of cell lysates of T. pallidum subsp. pallidum and T. pallidum subsp. pertenue. We tried to exploit the only known molecular difference between the subspecies. The subunits of the 190-kilodalton multimeric proteins TpF1 and TyF1 of T. pallidum subsp. pallidum and T. pallidum subsp. pertenue, respectively, have previously been shown to differ in one amino acid residue at position 40. In this study, no difference was found in immunoreactivity of TpF1 or TyF1 with either syphilis sera or yaws sera. Synthetic peptides based on the sequence of TpF1 and of TyF1 were used in an enzyme-linked immunosorbent assay with syphilis sera and yaws sera. Again, no difference in reactivity between the T. pallidum subsp. pallidum- and T. pallidum subsp. pertenue-derived peptides was observed. PMID- 2199523 TI - Ophthalmia neonatorum caused by Neisseria cinerea. AB - Neisseria cinerea is an organism that has only recently been implicated as a human pathogen. In this case, N. cinerea was identified as the cause of ophthalmia neonatorum (conjunctivitis) in a 2-day-old girl. PMID- 2199524 TI - Natural habitat of Cryptococcus neoformans var. gattii. AB - Environmental isolations have established that Cryptococcus neoformans var. gattii appears to have a specific ecological association with Eucalyptus camaldulensis. So far, we have isolated C. neoformans var. gattii on 35 separate occasions, all from samples associated with E. camaldulensis. The global distribution of E. camaldulensis appears to correspond to the epidemiologic distribution of cryptococcosis caused by C. neoformans var. gattii. No other environmental source for the fungus has yet been detected, and no other eucalypt has the distribution pattern corresponding to reported cases caused by this fungus. These findings may provided an explanation for the high incidence of infections caused by C. neoformans var. gattii in Australian aborigines living in the Northern Territory and for its low worldwide incidence in acquired immunodeficiency syndrome patients. PMID- 2199525 TI - Comparison of Vitek Gram-Positive Identification system with API Staph-Trac system for species identification of staphylococci of bovine origin. AB - Staphylococci (n = 130) of bovine origin representing 14 species were evaluated. Agreements of Vitek and API systems with conventional methods were 44.6 and 80.8%, respectively. The poor performance of the Vitek system was attributed primarily to inability to identify S. chromogenes. Incorporation of additional veterinary strains into the Vitek data base is needed to increase accuracy. PMID- 2199526 TI - Evaluation of the Directigen 1,2,3 Group A Strep Test for diagnosis of streptococcal pharyngitis. AB - The Directigen 1,2,3 Group A Strep Test (DGAST; BBL Microbiology Systems, Cockeysville, Md.) was compared with conventional culture methods for the detection of group A streptococci. Among 327 children, the DGAST has a sensitivity of 75.0%, a specificity of 99.1%, and positive and negative predictive values of 97.5 and 89.3%, respectively, as compared with 48-h culture results. The lower sensitivity (60.0%) in 322 adults was related to the low incidence of group A streptococcal pharyngitis in that population (7.8%). The positive and negative predictive values for adults were 93.8 and 96.7%, respectively. Only 3 of 327 (0.9%) pediatric and 2 of 322 (0.6%) adult specimens yielded uninterpretable results in the DGAST. PMID- 2199527 TI - Methanogenic bacteria in human vaginal samples. AB - Twelve vaginal samples were collected from separate patients, processed anaerobically, and added to methanogenic enrichment medium. Methanogenic activity was detected in two samples, both of which were from patients with bacterial vaginosis. None of the samples from healthy patients yielded positive methanogen cultures. One sample from a patient with bacterial vaginosis did not show any detectable methanogenic activity. Two methanogen isolates were obtained from one of the methanogen-positive samples, and both were identified as Methanobrevibacter smithii on the basis of morphological, cultural, and immunological features. PMID- 2199528 TI - Identification of a high-virulence clone of serotype III Streptococcus agalactiae by growth characteristics at 40 degrees C. AB - A high-virulence clone of serotype III Streptococcus agalactiae causing invasive neonatal disease was previously identified by multilocus enzyme electrophoresis. A simple procedure involving growth at 40 degrees C distinguished all isolates classified in this high-virulence clone from other serotype III isolates, which are more frequently associated with asymptomatically colonized infants, as well as the other serotypes of group B streptococci. The high-virulence clone failed to grow at 40 degrees C in FMC, a chemically defined medium, in contrast to the other organisms, which grew readily. PMID- 2199529 TI - Septicemia caused by vancomycin-resistant Pediococcus acidilactici. AB - A case of septicemia caused by vancomycin-resistant Pediococcus acidilactici is discussed. This appears to be the first reported case of septicemia caused by this organism. The characteristics and antimicrobial susceptibilities of this organism are described. PMID- 2199530 TI - Merifluor-Legionella cross-reactivity. PMID- 2199531 TI - Ploidy of smooth muscle tumours: retrospective image analysis study of formalin fixed, paraffin wax embedded tissue. AB - The feasibility of using an image analyser, the CAS 100, to assess the ploidy of smooth muscle tumours on formalin fixed paraffin wax embedded tissue was assessed. Various different methods of assessment were compared. A paraffin wax block of 15 leiomyomata and 13 leiomyosarcomata yielded serial sections of 3 microns, 5 microns, and 7 microns and a cytospin preparation (from a 50 micron section). Sections and cytospin preparations were stained with Feulgen and quantified using the CAS 100. The suitability of lymphocytes, previously suggested to be unsuitable as control cells in tissue sections due to the compact nature of their DNA, was assessed in sections and cytospin preparations and compared with endothelial cells, the standard alternative, on the same slide. Despite having a mean nuclear area of only 18.5 microns 2 in sections lymphocytes had a similar diploid peak--that is, 4.1 pg--to endothelial cells (mean nuclear area 39 microns 2). A comparison of 3 microns, 5 microns, and 7 microns sections showed 5 microns to be the optimal thickness. Cytospin preparations yielded histograms of superior quality than those from tissue sections. All 15 leiomyomata had a 5C exceeding rate of less than 0.3%. Ten of 11 histologically malignant tumours had a 5C exceeding rate of more than 5% (mean 14%) in sections and cytospins. Two leiomyosarcomata that had arisen in the lower gastrointestinal tract had a mitotic rate of less than or equal to 1/10 per high power fields and yielded histograms similar to those of the leiomyomata. It is concluded that formalin fixed, paraffin wax embedded tissue can be used for DNA quantification by image analysis; that tissue sections yield poorer results than cytospin preparations; that lymphocytes are reliable control cells in cytospin preparations; and that a population of cell greater than 5C is seen in 90% of leiomyosarcomata. PMID- 2199532 TI - Bone marrow biopsy in monoclonal gammopathies: correlations between pathological findings and clinical data. The Cooperative Group for Study and Treatment of Multiple Myeloma. AB - Between January 1987 and October 1989, 561 consecutive untreated patients with monoclonal gammopathy of undetermined clinical importance (MGUS) (n = 295) or with multiple myeloma (n = 266) were evaluated in a multicentre trial. Both bone marrow biopsy and aspiration (performed at different anatomical sites) were required at presentation. Bone marrow biopsy data indicated that changes in bone marrow composition from MGUS to early multiple myeloma and to advanced multiple myeloma followed a precise pattern, including an increased percentage of bone marrow plasma cells (BMPC%), a shift from plasmocytic to plasmoblastic cytology, an increase in bone marrow cellularity and fibrosis, a change in bone marrow infiltration (becoming diffuse rather than interstitial), a decrease in residual haemopoiesis and an increase in osteoclasts. In multiple myeloma the BMPC% of biopsy specimens and aspirate were closely related, although in 5% of cases the difference between the two values was greater than 20%. Some histological features were remarkably associated with each other. For example, BMPC% was higher in cases with plasmoblastic cytology, heavy fibrosis, or reduced residual haemopoiesis. Anaemia was the clinical characteristic most influenced by bone marrow histology. The BMPC% was the only histological variable which affected the greatest number of clinical and laboratory characteristics, including, besides haemoglobin concentration, erythrocyte sedimentation rate, radiographic skeletal bone disease, and serum concentrations of monoclonal component, calcium, beta 2 microglobulin and thymidine kinase activity. These data indicate that comparative bone marrow histology in monoclonal gammopathies has clinical importance. PMID- 2199533 TI - Microbiological investigations into an outbreak of Pontiac fever due to Legionella micdadei associated with use of a whirlpool. AB - In the investigation of a large outbreak of non-pneumonic legionellosis at a leisure complex in Lochgoilhead, Scotland all direct cultures of environmental samples were initially negative for legionellae. Legionellae readily infect appropriate protozoa under suitable conditions, and following immunofluorescence to select specimens for special study, Legionella micdadei was isolated from whirlpool water via co-cultivation with Acanthamoeba polyphaga. L micdadei was also isolated, along with host amoebae, from the whirlpool filter. The use of amoebae in the isolation of legionellae from environmental (and other) sources can be of great value, especially if specimens shown by indirect immunofluorescence to contain legionellae fail to yield legionellae on routine culture. PMID- 2199534 TI - Technique for identifying cutting artefacts in sections of undecalcified bone biopsy specimens. AB - Areas of fragmentation found in trabecular and cortical bone of iliac crest biopsy specimens have been described as bone quality defects and were thought to be the major factor responsible for femoral neck fractures. These appearances have also been regarded as cutting artefacts and to resolve this difference of opinion consecutive sections cut at right angles to each other in biopsy specimens from 15 patients with femoral neck fractures were compared. Sections were assessed by four independent observers; agreement by at least three was required before an area was accepted as a bone quality defect. In all, 270 were identified. Of the 161 found in sections cut parallel to the cortices, there were only 20 (12%) in coincident areas in consecutive sections. This study shows conclusively that areas of fragmentation previously described as bone quality defects are not artefacts which may be created or excluded depending on the plane of section. PMID- 2199535 TI - Immunocytochemical detection of Helicobacter pylori in formalin fixed tissue biopsy specimens. PMID- 2199536 TI - Multiple drug resistance in salmonellae in England and Wales: a comparison between 1981 and 1988. AB - Each year from 1981 through to 1988 the most common serotypes isolated from man in England and Wales and identified at the Division of Enteric Pathogens were S typhimurium, S enteritidis, and S virchow. In 1981 these three serotypes accounted for 45%, 12%, and 7% of isolations. The remaining 35% comprised strains belonging to a further 188 different serotypes, none of which accounted for more than 1% of the total. In 1988 S typhimurium accounted for 24% of isolations, S enteritidis 57%, and S virchow 4%. The remaining 15% comprised strains of a further 184 serotypes. The resistances to the common antimicrobial drugs in non typhoidal salmonellas isolated in England and Wales in 1981 and 1988 were reported with particular reference to resistance to four or more antimicrobial drugs (multiple resistance). For S typhimurium the overall percentage of resistant strains varied little, but multiple resistance more than doubled from 5% to 12%; in S enteritidis the incidence remained the same. In S virchow the percentages of strains resistant to all the antimicrobial drugs and in particular, to chloramphenicol, streptomycin, trimethoprim and furazolidone, rose from 0.2% to 10.4%. Salmonella enteritis in man is usually a self limiting disease and antimicrobial treatment is seldom required; but should spread beyond the intestine occur, effective antimicrobial treatment is essential. Under these circumstances a knowledge of the likelihood of resistances to commonly available drugs could be of considerable value to the clinician. PMID- 2199537 TI - Evaluation of two rapid methods for identifying and biotyping Haemophilus influenzae. AB - Several rapid method kits (one to four hours) have become available for the identification of Haemophilus and related genera. Two kits (the "Rapid NH" system and the "RIM Haemophilus" system), which include the identification and biotyping of H influenzae, were investigated for the rapid identification and biotyping of 193 isolates of H influenzae and the results compared with those obtained by more standard overnight methods. The kits were convenient to use and gave reliable and rapid speciation of all isolates. Both test systems were unreliable for biotyping: 42 isolates were wrongly biotyped by the RIM kit and 40 isolates wrongly biotyped by the rapid NH kit. It is concluded that the test kits may be useful for the rapid identification of H influenzae but that they are not reliable for the biotyping of this species. PMID- 2199538 TI - Evaluation of Cathra system for identifying gram negative aerobic bacteria. AB - The Cathra system is a commercial multipoint inoculation method for the identification of aerobic Gram negative bacteria. The system uses a replicator technique in which 21 different agar media can be inoculated simultaneously with 36 organisms. Identifications are made by use of a special computer database. The performance of this system was compared with that of the API 20E for the identification of 372 clinical isolates of Enterobacteriaceae and 133 miscellaneous Gram negative bacteria. For enterobacteria, the Cathra system was in 97% agreement with API 20E at species level and 98% at genus level. For miscellaneous Gram negative strains the two systems were in 59% agreement at species level and 77% at genus level. The Cathra system is suitable for use in diagnostic laboratories, especially those with a heavy workload and a wish to use break-point sensitivity testing. The identification database for miscellaneous Gram negative organisms, however, needs to be expanded. PMID- 2199539 TI - Does delay in fixation affect the number of mitotic figures in processed tissue? AB - The effect of delay in fixation on the number of mitotic figures in tissues has received little attention, and previous studies have reached differing conclusions. The numbers of mitotic figures in the normal mucosa of six colectomy specimens were counted with delays in fixation of 30 minutes, one hour, two hours, three hours and six hours for samples from each specimen. The numbers of mitotic figures were counted in 50 whole crypts in each specimen by two observers. All phases of mitosis were counted. The number of observable mitotic figures declined by about 30% with a delay in fixation of two hours and by 50% with a delay of six hours. This observation has important implications for the handling of surgical specimens. PMID- 2199540 TI - Use of benzidine for histological demonstration of haemoglobin in human bite marks. AB - Macroscopic evidence of bruising from human bite marks may be inconclusive and routine histochemical methods of showing extravasated erythrocytes can be unreliable. Leuco patent blue staining, for the presence of peroxidase, Amido black B, a tinctorial staining method for haemoglobin, Perls's reaction for ferric iron (haemosiderin), Masson-Fontana for melanin, Masson's trichrome, a connective tissue strain, and the benzidine reaction for haemoglobin peroxidase were carried out in three forensic cases and one experimental case. A modified benzidine method was the most reliable indicator of haemoglobin activity, especially where dispersion into extra-cellular tissues had occurred. The resilience of the erythrocyte peroxidase enzyme to temperature changes and fixation supports the concept of a "pseudo-peroxidase" in those cells. It is concluded that free haemoglobin from bite marks, or indeed other forms of blunt trauma, may best be shown by the benzidine reaction and that exemption certificates for use of this prohibited substance may be worth pursuing. PMID- 2199541 TI - Congenital malaria in one identical twin. PMID- 2199542 TI - Survival of Helicobacter pylori in water and saline. PMID- 2199543 TI - Nutrition in the curriculum: medical experience. AB - Nutrition in the Curriculum--Medical experience, current practices, and educational status in U.S. medical schools are briefly reviewed. There continues to be a need for more adequate instruction of clinical nutrition to physicians in training and in practice. A major problem is the failure to provide patient oriented, case-related, nutrition teaching in the clinical years to all clinical clerks. Desirable changes are listed to help achieve better training in this field. PMID- 2199544 TI - Applied nutrition in dental education; issues and challenges. PMID- 2199546 TI - Cicatricial pemphigoid with linear IgA deposit. AB - A Japanese woman with typical clinical and histological manifestations of cicatricial pemphigoid was presented. Direct immunofluorescent (IF) investigation of perilesional skin revealed in vivo deposits of IgA but not of IgG, IgM, or C3. Indirect IF study revealed that this patient had circulating antibody against epidermal basement membrane zone of the IgA class. We would like to classify this case as cicatricial pemphigoid with IgA deposits rather than as a cicatricial variant of linear IgA bullous dermatosis. PMID- 2199545 TI - Urinary incontinence: managing the problem. PMID- 2199547 TI - Direct estimation of aberrating delays in pulse-echo imaging systems. AB - Nearfield fluctuations in wave propagation velocity and system timing errors are among the sources of focusing aberrations in pulse-echo imaging systems. For situations in which the source of these errors can be modeled by a stationary phase aberrator placed in front of the transmitter and receiver aperture, appropriate electronic delays might be applied to the signals associated with each array element in order to restore the system to focus. A method is described and evaluated for estimating the set of aberrating delays in a linear array utilizing data from a single two-dimensional scan. The underlying principle is analogous to that of phase closure used for one-way passive interferometry and readily generalizes to two-dimensional arrays. Although the following theory is developed in the context of acoustic imaging, the general approach is applicable to other pulse-echo systems, such as radar. PMID- 2199548 TI - Increased heating by diagnostic ultrasound due to nonlinear propagation. AB - The heating of tissues by the absorption of ultrasound is an important safety consideration in the use of diagnostic ultrasound. This paper shows that models of ultrasonic heating for this situation need to take account of nonlinear propagation. Measurements were made of the temperature rise in a sample of tissue mimicking gel, caused by the application of 3.6-MHz focused ultrasonic beams for 3 min. The propagation path to the focus was in water, to mimic the situation where the fetus is scanned through the full bladder. The effect of nonlinear propagation was seen by changing the pressure amplitude of the pulse, while altering the pulsing regime to preserve a constant spatial-peak temporal-average intensity of 1 W cm-2. When nonlinear distortion was present, an enhancement in the temperature rise was observed, which correlated with the value of the shock parameter. The enhancement ratio was typically up to a factor of 3, and the maximum temperature rise observed was 2 degrees C. This enhanced heating was seen both at the surface of the tissue-mimicking gel and after propagation through 23 mm of the material. Under conditions of nonlinear propagation, the maximum heating usually occurs in the prefocal region, rather than at the focus. PMID- 2199549 TI - Medicaid regulations for long-term care. PMID- 2199550 TI - Will Medicaid parity follow Medicare parity? PMID- 2199551 TI - Comprehensive vision care under third party programs: increased services and increased scrutiny. AB - Physician reimbursement under Medicare has been rising by about 15 percent each year. Part of this increase is due to an increase in unnecessary tests and procedures. To control provider billing, Congress passed legislation that will establish a Medicare fees schedule and expenditure targets. Increased surveillance and monitoring of Medicare claims are taking place. Diagnostic procedures are being questioned and denied when deemed inappropriate in relation to a diagnosis. Managed care techniques also are being implemented by private insurance carriers to prevent overutilization. Clinic practice guidelines are being developed by the health professions. Optometry, as well as all other health professions, will be subject to increased utilization and quality review. PMID- 2199552 TI - A review of non-retinal ocular complications of diabetes mellitus. AB - Significant attention is paid to the retinal complications of diabetes mellitus and their potentially devastating effects on vision. Diabetes mellitus, however, is a multisystem disease, and diabetic eye disease is an end-organ response to the effects of the condition on the human system. Each portion of the eye is susceptible to the harmful effects of diabetes. This article reviews diabetic effects on non-retinal ocular structures and provides references for those interested in pursuing further studies on diabetic eye disease. PMID- 2199553 TI - Management of infantile-onset esotropia. AB - Background information on the prevalence, clinical characteristics, and differential diagnosis of infantile-onset esotropia is presented. A brief overview of early development of binocularity is also presented to set the stage for management, as well as a sequential treatment plan for two age groups of infantile esotropes: 1) infants and toddlers, and 2) preschool and "older" patients. Flowcharts and case examples are included to highlight the management principles for attaining maximum binocular function. PMID- 2199554 TI - Mutagenicity and genotoxicity of ethylvinyl ketone in bacterial tests. AB - The mutagenic and genotoxic effects of ethylvinyl ketone were investigated. This alpha, beta-unsaturated carbonyl compound is widely distributed in the environment, in particular in food. Whereas ethylvinyl ketone shows only weak genotoxicity in the SOS Chromotest with Escherichia coli PQ37, it was distinctly mutagenic per se in the Salmonella preincubation assay with TA100. Using SKF 525 (an inhibitor of microsomal monooxygenase) and trichloropropene oxide (an inhibitor of epoxide hydrolase) we found indication for additional activation via epoxidation by S9 mix. The need for further investigation of the genotoxic, mutagenic and carcinogenic effects of this compound is strongly indicated. PMID- 2199555 TI - Traumatic dislocations of the tibialis posterior tendon: a review of the literature and two case reports. AB - Dislocation of the tibialis posterior tendon from behind the medial malleolus is a very rare lesion. The authors present two cases of this pathology with special reference to surgical correction. Historical review, mechanism of injury, diagnosis, and treatment will also be discussed. PMID- 2199556 TI - Effectiveness of an epineurial barrier in reducing axonal regeneration and neuroma formation in the rat. AB - Neuroma excision is a common surgical practice that typically leads to axon regeneration and/or Schwann cell overproliferation from the proximal nerve stump. The effectiveness of the epineurium as a barrier to this reaction to nerve severing was studied in 31 rats. The right sciatic nerve was severed in each case. Control groups that had no further treatment displayed typical neuromas with axon regeneration 3, 6, and 8 months postoperatively. Experimental groups that had a "cap" of epineurium microsutured tightly over the proximal stump displayed significantly reduced neuromas up to 8 months postoperatively. PMID- 2199557 TI - Tumoral calcinosis of the foot: case report and literature review. AB - Soft tissue tumors occur in all parts of the body. Once identified, they must be thoroughly evaluated and treated. Tumoral calcinosis is a metabolic disorder that presents as a soft tissue deposit near large joints in the body. Occasionally, it may occur in the foot and become symptomatic. Once the etiology and pathophysiology is understood, the proper course of treatment may begin. PMID- 2199558 TI - [Sports and pregnancy. A review of the literature]. AB - A review of the literature concerning sport during pregnancy is presented. The mother's heart rate, arterial blood pressure, systolic ejection fraction and cardiac output undergo the same changes during exercise in the pregnant and non pregnant patient. The increase in the fetal heart rate during maternal physical exercise does not adversely affect the fetal outcome. The uterine blood flow is diminished during exercise. The respiratory rate increases equally in pregnant and non-pregnant women. The maternal response to effort is also modified by weight gain during pregnancy, by changes in the musculo-skeletal system, and by maternal temperature control during exercise. Weight gain, uterine contractility, duration of pregnancy, labour and neo-natal conditions are not altered by sport during pregnancy. Contra-indications to sport during pregnancy include threatened premature labour, and conditions associated with an increased risk of prematurity. A previous history of fetal growth retardation, acute fetal distress, or the presence of diabetes or arterial hypertension is a contra indication to sport during pregnancy. The advice which should be given to a pregnant woman wishing to continue her sporting activities during pregnancy is outlined. PMID- 2199559 TI - [Multiple pregnancies. II. Epidemiology, clinical aspects]. AB - It used to be rare for multiple pregnancies to occur but we have seen a spectacular rise in them in France between 1970 and 1986. Triplet deliveries increased threefold. The authors analyse a personal series of 23 pregnancies (19 triplets, 3 quadruplets and 1 quintuplet pregnancy). Sixteen of these 23 were medically induced. The main complications that have been observed were: threatened premature delivery in 86%, high blood pressure in 34.7%, anaemia in 50%, and urinary tract infections in 30.4%, 6.8% of the babies had congenital malformations. Reviewing the literature has made it possible to discern the epidemiological factors causing multi-fetal pregnancies: family history, high female fertility, maternal age, ethnic factors, hormonal contraception etc... At present it is medically assisted reproduction that is the big supplier of multi fetal pregnancies in developed countries. We have reviews of several maternal as well as fetal complications: the ovarian hyperstimulation syndrome, extra-uterine pregnancy, hypertension, anaemia, spontaneous abortion, prematurity, intra uterine growth retardation and malformations. PMID- 2199560 TI - [Diaphragmatic hernia and pregnancy]. AB - Congenital or traumatic hernia complicating pregnancy is a rarity but death occurs in half of the cases. Complications (respiratory distress, intestinal obstruction) are more frequent during the third trimester, during delivery and in the post-partum hours. In the asymptomatic patient, surgery should be performed specially in the first and second trimesters. During the third trimester, fetal maturity should be watched and the defect should be repaired at the time of elective cesarean section. Active labor should be avoided because of the increased abdominal pressure produced during the expulsion period. If an unexpected labor occurs, forceps application, if cesarean section could not be performed, should be realised. If signs of respiratory distress or of obstruction arise at any time, immediate repair should be undertaken, regardless of the age of pregnancy. An hernia operated before the pregnancy could recur during this one (this is the case of the author). Il is possible that some diaphragmatic hernias no complicated during previous pregnancies could be aggravated without symptoms and are complicated during a further pregnancy. PMID- 2199561 TI - [Meta-analysis as a synthesis of clinical and epidemiologic information. Its application to treatments in gynecology and obstetrics]. AB - Multiple clinical studies require a structured synthesis of their results, especially where heterogeneous results are reported. Meta-analysis is a method that does just that. Such an epidemiological study of results across studies replaces the traditional narrative review of literature, and its study completes, but does not replace medical record linkage. Diuretics in pre-eclampsia, progestational agents in the control of major failures of pregnancy and fetal monitoring as a possible trigger for more frequent caesarean sections are given as examples of interest in gynaecology and obstetrics. PMID- 2199562 TI - [Is sexual abstinence a factor in the etiology of chromosome abnormalities?]. AB - Some epidemiological and experimental data in mouse have suggested that there could exist a relationship between sexual abstinence duration and occurrence of chromosomal disorders. In order to determine whether sexual abstinence exerts an effect on the incidence of chromosomal abnormalities in Human, sperm chromosome complements of 4 men were analyzed after fusion with golden hamster eggs. The period of abstinence ranged from 2 days to 15 days. Seven hundred and seventy five karyotypes were obtained. The overall frequency of abnormalities was 9.4% that is not different from controls. There was no correlation between the length of the sexual abstinence and each type of chromosomal abnormality but an indirect effect of paternal aging cannot be excluded. PMID- 2199563 TI - [The diagnosis of a pseudo-unicornous uterus. Apropos of a pregnancy in a rudimentary uterine horn]. AB - The following is a report of an unusual case of a patient who had a rupture of the rudimentary horn at 21 weeks of pregnancy. Hysterography had shown that she had a unicornuate uterus but she had not had a laparoscopy. Later ultrasound pictures at the beginning of pregnancy failed to reveal that the pregnancy sac was ectopic. The authors also stress the absolute need to carry out laparoscopy in cases of unilateral Mullerian hypoplasia. They show how to read ultrasounds in cases of pregnancies in rudimentary horns. They try to point out the best procedures for diagnosis using the literature. PMID- 2199564 TI - [Icteric complications related to pregnancy vomiting in the 1st trimester (hyperemesis gravidarum). Review of the literature apropos of a case]. AB - The authors report a case of jaundice occurring secondary to severe vomiting in pregnancy in the first trimester. This is a rare clinical entity (occurring in 0.2-3 cases per thousand) although some people say it does not exist. The physiopathology is still badly understood but it occurs most often between the fourth and eighth week of amenorrhoea. It is characterised by jaundice occurring secondarily to vomiting in the first trimester, with a rise in the bilirubin level in the blood and in the alkaline phosphatases. Sometimes there is a slight rise in the transaminases. The diagnosis can only be arrived at after having excluded all the other possible causes of jaundice which are mentioned in the text. Furthermore the way the condition progresses is an important argument for its aetiology because once vomiting ceases the jaundice goes. The treatment has to be symptomatic with correction of the dehydration. PMID- 2199565 TI - [Parkinson disease and pregnancy. Apropos of a case]. AB - Parkinson's disease is a neurological condition associated with neuronal degeneration in the corpora nigra with a drop in the level of dopamine in the striatum. It is rarely encountered in women of reproductive age. Treatment is by giving levodopa. We report a case of pregnancy in a woman of 34 years of age who was suffering from severe Parkinson's disease treated with levodopa. We have assessed this case in the light of viewing the literature which confirms that there is no effect on the pregnancy or on the fetus although the symptoms of Parkinson's disease are made worse. Levodopa seems to be quite innocuous as far as the fetus is concerned. There is no teratogenicity although in animal experiments high doses teratogenic effects have been noted. PMID- 2199567 TI - [Macrosomia and maternal insulinemia in gestational diabetes]. AB - Macrosomia is an important cause of neonatal morbidity. To detect the utility of plasma insulin level to predict neonatal macrosomia, we studied the glycemic and insulin responses to 100 g oral glucose tolerance test (OGTT) in 57 gestational diabetic women on diet therapy. Ten (17.5%) of them had macrosomic newborns. Macrosomia was defined as a birthweight higher than the 90th centile on our population scale. The mothers of the macrosomic newborns exhibited similar parity, body mass index, gestational age at OGTT and at delivery. Fasting capillary plasma glucose value was higher in women with macrosomic newborns (5.3 mmol/l +/- 0.4 vs 4.8 mmol/l +/- 0.4; p less than 0.01) as well as fasting capillary plasma insulin concentration (28.7 mU/L +/- 9.3 vs 17.7 mU/L +/- 6.4; p less than 0.01). The fasting glucose value was found to be more accurate than fasting insulin concentration to predict macrosomia (logistic regression and discriminant analysis). Thus, measuring insulin concentrations during an OGTT seemed to be unhelpful to predict macrosomia in gestational diabetic women. PMID- 2199566 TI - [Magnetic resonance imaging in the evaluation in utero of Siamese twins]. AB - The authors report a case of twins conjoined at the umbilicus and diagnosed by ultrasound after 19 weeks of amenorrhoea in whom an assessment in utero was carried out using magnetic resonance imaging after the patient had been curarized. A review of the literature on this very difficult problem of conjoined twins has given us the possibility to assess the diagnostic measures as well as the prognosis of this pathology. In particular we point out the results that can be obtained using MRI in utero during the second and third trimesters of the pregnancy. PMID- 2199568 TI - [A uterine cleft with a digestive intra-uterine adhesion detected during a cesarean section at term]. AB - A gap in the wall of the uterus that was discovered by chance during a Caesarean operation carried out at term for a twin pregnancy is reported. This gap was accompanied by adhesion of the digestive tract within the uterus. After the adhesions had been cut away the gap was sutured. The reason for this pathological condition was suction evacuation at termination of pregnancy. We could find no reference in the literature to the combination of such a gap with a pregnancy that continued normally. PMID- 2199569 TI - Thermal self-regulation for pain control in reflex sympathetic dystrophy syndrome. AB - Reflex sympathetic dystrophy syndrome is comprised of a variety of changes in vasomotor and trophic responsivity, as well as, stiffness, edema and severe pain. This study examined 20 patients with reflex sympathetic dystrophy syndrome who had failed to respond to a variety of techniques commonly used to treat this disorder. These patients had documented histories of reflex sympathetic dystrophy syndrome ranging from 18 to 60 months. All had been referred for psychological evaluation and provision of pain management. A combination of thermal biofeedback, relaxation training, and supportive psychotherapy were used to reduce subjective pain. The results indicate that patients were able to significantly increase their initial (p less than 0.0001) and postrelaxation (p less than 0.0001) hand temperatures, as well as to significantly reduce their subjective pain ratings (p less than 0.0001). This reduction in pain was maintained at 1-year telephone follow-up, with 14 of the 20 patients returning to work by that time. This intervention was effective as a pain reduction strategy for our patients with reflex sympathetic dystrophy syndrome who had failed to benefit from other treatments. PMID- 2199570 TI - Barber's interdigital pilonidal sinus of the hand: a foreign body hair granuloma. AB - Interdigital pilonidal sinus of the hand is an occupational disease of male barbers. Customers' hairs penetrate the supple interdigital skin, cause a sinus, and later a cyst. Through the sinus, the hairs get entrapped and may occasionally be expressed. Excision of the sinus or the cyst is curative. PMID- 2199571 TI - Chondrosarcoma of small bones of the hand arising from enchondroma. AB - We report the clinicopathologic findings in two cases of chondrosarcoma of the small bones of the hand arising from a preexisting solitary enchondroma. A critical review of the previously reported 18 cases shows that only one is actually well-documented. PMID- 2199572 TI - Ramazzini and occupational diseases. PMID- 2199573 TI - The 1988 Bunnell traveling fellow report. PMID- 2199574 TI - High permeability pulmonary oedema: pathophysiology and mechanisms of injury. AB - Many critically ill patients are at risk for developing HPPE. Since 60% of patients develop HPPE within 24 hours of the pulmonary insult with 11% developing respiratory failure within 72 hours, it is imperative that the critical care nurse understand the pathophysiological responses (Bernard & Bradley, 1986). While the pathophysiological responses are specific, injury to the alveolar capillary membrane, the mechanisms of injury are diffuse. Knowing the mechanisms can alert health care providers to those patients who are at risk for developing HPPE and more quickly mobilize interventions to alleviate or lessen its occurrence. PMID- 2199575 TI - Pharmacokinetic and pharmacodynamic effects of a single nocturnal dose of alprazolam. AB - Six healthy volunteers participated in a study of the pharmacokinetic and psychomotor effects of a single dose of 2 mg of alprazolam compared to placebo when given at night. Alprazolam reached a maximum concentration in the plasma between 0.5 and 2.5 h after the dose. It was extensively distributed to the tissues as shown by the large apparent volume of distribution (1.42 l/kg) and slowly eliminated (t1/2 = 13.7 h). Significant impairment of choice reaction time occurred 1 and 11 h after the dose of alprazolam compared to placebo. Critical flicker fusion was also impaired after alprazolam but the difference from the placebo administration did not reach significance. PMID- 2199576 TI - On the species specificity of the interaction of LFA-1 with intercellular adhesion molecules. AB - Species restrictions in immune cell interactions have been demonstrated both in Ag-specific responses of T lymphocytes and the phenomenon of natural attachment. To determine the possible contribution of adhesion receptors to these restrictions, we have studied binding between the murine and human homologues of LFA-1 (CD11a/CD18) and ICAM employing purified human LFA-1 and ICAM-1 (CD54) bound to solid substrates. Murine cell lines bind to purified human LFA-1 through ICAM-1 and at least one other counter-receptor. This provides evidence for multiple counter-receptors for LFA-1 in the mouse as well as in the human. In contrast to binding of murine ICAM-1 to human LFA-1, murine LFA-1 does not bind to human ICAM-1. The species specificity maps to the LFA-1 alpha subunit, because mouse x human hybrid cells expressing the human alpha subunit associated with a mouse beta subunit bind to human ICAM-1, whereas those with a human beta subunit associated with a murine alpha subunit do not. Increased adhesiveness for ICAM-1 stimulated by phorbol esters could be demonstrated for hybrid LFA-1 molecules with human alpha and murine beta subunits. PMID- 2199577 TI - Analysis of glycosylation changes in IgG using lectins. AB - A simple rapid assay based on the ability of lectins to bind carbohydrates has been developed to analyse changes in the oligosaccharide chains of IgG. Bandeiraea simplicifolia lectin and Ricinus communis agglutinin have been used to detect terminal N-acetylglucosamine and galactose moieties respectively in IgG using immunodot-blotting. IgG samples (approximately 1 micrograms) were dot blotted onto nitrocellulose followed by boiling of the blots to expose the carbohydrate moieties. The blots were then treated with biotinylated lectins followed by either streptavidin-biotin-hydrogen peroxidase conjugate or 125I labelled streptavidin. The colour was developed using chloronaphthol and the blots read on a densitometer. The labelled blots were cut and read on a gamma counter. The use of a monoclonal antibody to N-acetylglucosamine is also discussed. The results obtained using this method are comparable to those obtained by structural analysis. PMID- 2199578 TI - Enzyme-linked immuno-filtration assay applied to accelerated immunodetection of gel transferred proteins on immobilizing matrices. AB - The enzyme-linked immunofiltration assay (ELIFA) has been used for the rapid detection of electrophoresed proteins transferred from gels to immobilizing matrices. By controlled filtration, ELIFA permits the saturation of nylon or nitrocellulose membranes and the immunodetection of blotted antigens to be carried out in 15 min. The method is simple, can be automated and requires no handling of membranes. It complements the well standardized steps of gel electrophoresis and semi-dry horizontal electroblotting which can themselves be carried out in less than an hour. The sensitivity is at least 1-5 ng. The same process can be extended to the accelerated characterization of glycoproteins using appropriate ligands, or to the identification of antigens in a variety of biological fluids. PMID- 2199579 TI - Removal of liposomes with incompletely encapsulated enzyme using a monoclonal anti-alkaline phosphatase immunosorbent. PMID- 2199580 TI - Chromatographic enzyme immunoassay for T-2 toxin. AB - Both the active ester and maleimide moieties of the cross-linking reagent, N [(gamma-maleimidobutyryl)oxy]succinimide (GMBS), were found to react with the primary amino groups on ribonuclease (RNase). This largely inactivated RNase towards a polymeric (but not monomeric) substrate. Citraconylating the RNase first, so that essentially only a single primary amino group remained to react with GMBS, overcame this problem. The subsequent maleimido-citraconyl-RNase was used to prepare a 1:1.1 M conjugate of anti-T-2 toxin Fab' and RNase (Fab'-RNase) in a 76% yield. The conjugate was used to detect as little as 0.1 microgram of T 2 toxin based on the ability of T-2 toxin to specifically displace Fab'-RNase complexed to a T-2 agarose affinity gel. PMID- 2199581 TI - A fast and efficient method for quantification of monoclonal antibodies in an ELISA using a novel incubation system. AB - We have developed a sensitive, reliable, optimized ELISA to measure human IgM monoclonal antibodies using a novel shaking incubator system with short incubation periods of 15 min at 37 degrees C for all stages. The shaking incubator is compared with a static incubator over a range of incubation times and temperatures. For each stage using static incubation conditions the system does not reach a saturation level and the results are inconsistent, unlike the shaking incubator. No 'edge effects' are observed in the shaking system due to even heating from beneath and across the plate. The orbital shaking ensures optimal mixing of reagents which eliminates a diffusion limited reaction rate caused by a depletion of reactants at the solid phase as observed in the static system. The optimized shaking system permits economical use of reagents since the coating antibody can be used at high dilutions. PMID- 2199583 TI - Expression of basic fibroblast growth factor (bFGF) in Kaposi's sarcoma: an immunohistologic study. AB - Ten cases of Kaposi's sarcoma (KS) including five AIDS-KS, one classical KS, and four pseudo-KS (acroangiodermatitis) were investigated for their expression of basic fibroblast growth factor. Antigen expression was demonstrated by immunoperoxidase staining of cryostat sections with affinity-purified anti-bFGF antibodies. It was found that bFGF was strongly expressed in basal and suprabasal keratinocytes, which were also intensively stained in normal skin biopsies. The growth factor was generally absent from the endothelial cells and spindle cells of the neoplasms. These cell types exhibited a very faint staining in a small number of lesions. The studies provide strong evidence that proliferation of KS tumor cells may not be explained by autocrine secretion mechanism of the growth factor, which has been suggested in previous reports with in vitro cultured KS cell lines. PMID- 2199582 TI - Recombinant human cytokines stimulate neutrophil adherence to IgG autoantibody treated epithelial basement membranes. AB - We investigated the ability of the purified recombinant human cytokines: tumor necrosis factor-alpha (rTNF), granulocyte-macrophage colony-stimulating factor (rGM-CSF), interleukin-1 beta (rIL-1), interleukin-3, and tumor necrosis factor beta (rTNF-beta) to stimulate neutrophil adherence (NA) to basement membranes (BMs) of stratified squamous epithelia pretreated with autoantibodies (ABM) specific for the BM matrix protein, type-VII collagen. rTNF, rGM-CSF, rIL-1, and rTNF-beta, but not IL-3, stimulated NA and stimulation was ABM- and cytokine concentration-dependent. Stimulation was cytokine-specific and not due to endotoxin since it was significantly inhibited by cytokine-specific antibodies but not by polymyxin B (PB). rTNF and rGM-CSF were the most potent stimulators, were effective at concentrations less than 0.067 ng/ml, and stimulated NA greater than 600%. Relative potency was: rTNF = rGM-CSF greater than rTNF-beta greater than rIL-1. Stimulation by rTNF was due to a rapid, time-dependent effect on the neutrophil, and NA appeared to be dependent, in part, on the low-affinity neutrophil receptor for IgG, Fc(gamma)RIII, because it could be specifically inhibited by monoclonal antibody (3G8) to Fc(gamma)RIII. These results suggest that rTNF, rGM-CSF, rIL-1, and rTNF-beta may contribute individually or in combination to immune-mediated inflammation and tissue injury by stimulating immune adherence of neutrophils to tissue-bound autoantibodies and immune complexes. PMID- 2199584 TI - [Fundamental structure of group I intron ribozyme]. PMID- 2199585 TI - [Induction of rheumatoid factor-like substance and synovial lining cell hyperplasia in rats immunized with heat-killed Escherichia coli 0:14]. AB - Histological changes in the ankle joints and serum anti-IgG rheumatoid factor like substance detected by enzyme-linked immunosorbent assay (ELISA) were investigated in Sprague Dawley (SD), Wistar, and Lewis rats immunized with heat killed Escherichia coli 0:14. Synovial lining cell hyperplasia was observed in 23 of 46 joints and pannus formation in 7 of 46 joints in SD rats immunized for 29 weeks. RFLS levels were elevated from the 15th, 7th, and 5th week of immunization in rats receiving doses of 0.1, 1, and 10 mg of E. coli respectively, and remained elevated dose-dependently. RFLS levels in SD and Wistar rats were significantly higher (p less than 0.01) than in Lewis rats during the period from the 7th to the 13th week of immunization. These results imply that immunization of rats with E. coli induces arthritic changes in the ankle joints and produces RFLS in the serum in a dose-dependent and different manner in each rat strain. PMID- 2199586 TI - [The concept of and countermeasures in refractory anemia]. PMID- 2199587 TI - [A case of recurrent hepatitis A due to autoimmunity]. PMID- 2199588 TI - Prediction of implantation by the sonographic appearance of the endometrium during controlled ovarian stimulation for in vitro fertilization (IVF) AB - The texture and the thickness of the endometrium as assessed by transvaginal sonography were prospectively evaluated in 123 patients undergoing IVF treatment. Three different types of endometrial patterns could be distinguished: (A) an entirely homogenous, hyperechogenic endometrium; (B) an intermediate type characterized by the same reflectivity of ultrasound as the myometrium, with a nonprominent or absent central echogenic line; and (C) a multilayered endometrium consisting of prominent outer and midline hyperechogenic lines and inner hypoechogenic regions. On the day before oocyte retrieval, endometrial thickness was significantly greater in the group of patients who achieved pregnancy than in the group who did not (8.7 +/- 0.4 vs 7.5 +/- 0.2 mm, respectively; P less than 0.01) and significantly more patients had multilayered, pattern C, endometrium (75% in pregnant women vs 42.4% in nonpregnant women; P less than 0.01). No pregnancy occurred when the endometrial thickness was less than 6 mm. When type C endometrium greater than or equal to 6 mm thick was seen, the pregnancy rate per embryo transfer was 39%. When type A or B endometrial pattern was seen, the negative predictive value for the occurrence of pregnancy was 90.5%. Our results suggest that transvaginal sonographic evaluation of endometrial texture and thickness may be an indicator of the likelihood of achieving pregnancy. PMID- 2199589 TI - Trimetazidine and stable angina a double-blind trial. AB - The effect of trimetazidine was evaluated in patients with stable angina by adding it to the other antianginal regimen in a double blind crossover design each of 8 week's duration. The method of evaluation made use of symptom recall, daily dairy of the intake of sublingual nitrates or of anginal discomfort and in some, symptom limited treadmill exercise stress test (EST). Thirty-six patients completed the trial. Symptom-wise, 16 patients could not differentiate the effect of the true tablet from the placebo. Eight had less and 12 had more angina while on the drug. Of the 17 evaluable EST, 9 showed no change in the degree of ischemic changes while 4 performed with less and 4 with more ischemia while on the drug. Symptom-wise and taking into account the pre and post trial periods, a placebo effect was not found to be dominant. It is concluded that trimetazidine does not improve angina among those already being treated with conventional doses of nitrates, beta and calcium blockers. PMID- 2199590 TI - A gonadotrophin surge attenuating factor? PMID- 2199591 TI - Immunohistochemical localization of androgen receptors with mono- and polyclonal antibodies to androgen receptor. AB - Rat, human, and mouse tissues were stained immunohistochemically using mono- and polyclonal androgen receptor antibodies. Monoclonal antibodies were raised in rats and used to stain human and mouse tissues; polyclonal antibodies were raised in rabbits and used to stain rat tissues. Frozen tissue sections were incubated with the appropriate androgen receptor antibody and staining was completed by the indirect avidin-biotin peroxidase method. A comprehensive survey of rat and mouse tissues was performed. Antibody staining was found exclusively in the nucleus of certain specific cell types, suggesting that the androgen receptor is a nuclear protein. All male sexual organs in the rat showed strong positive nuclear staining for androgen receptor. Weaker positive reactions were seen in kidney, liver, adrenal cortex and pituitary gland. Furthermore, positive staining for androgen receptor was exhibited in skeletal, cardiac and smooth muscle cells, and central nervous tissue. Female reproductive organs also contained androgen receptor-positive cells. The spleen was found to be the only organ examined which did not stain for androgen receptor. The monoclonal antibody could also demonstrate androgen receptor-positive cells in a human prostatic cancer and in a prostate with benign hyperplasia. These data demonstrate the use of antibodies in revealing cellular/subcellular distribution of androgen receptor in target tissues. PMID- 2199592 TI - Carnitine: metabolism, function and clinical application. PMID- 2199594 TI - Transport and functions of carnitine in muscles. AB - The transport, function and metabolism of carnitine are discussed with regard to their importance in clinical chemistry. In humans carnitine is synthesized from protein-derived trimethyllysine in liver, brain and kidney. Muscles take up carnitine from the blood in an exchange-diffusion process with endogenous deoxycarnitine, the immediate precursor of carnitine. Besides catalysing the transport of long-chain acyl groups in mitochondria, carnitine is necessary for the export of intramitochondrially produced short-chain acyl residues and for the trapping and the elimination of unphysiological compounds (benzoic, pivalic, valproic acids etc.). The detection and quantitation in urine of these physiological and unphysiological carnitine esters is necessary for the diagnosis of carnitine deficiencies. The carnitine esters may be eliminated in the urine and/or distributed in tissues, where some of them (acetyl-, propionyl- and isovaleryl-carnitine) may be utilized for specific purposes. The most important carnitine-dependent metabolic disorders are listed according to their causes. PMID- 2199593 TI - The role of carnitine in intracellular metabolism. AB - In animal cells long chain fatty acids are transferred into the mitochondria for oxidation as acylcarnitines. Carnitine palmitoyltransferase I in the outer membrane, and carnitine translocase plus carnitine palmitoyltransferase II in the inner membrane catalyse the transfer. Carnitine palmitoyltransferase I is inhibited by malonyl-CoA, an intermediate in fatty acid synthesis. In the liver of fasted, diabetic, or thyreotoxic animals this enzyme shows increased activity and less inhibition by malonyl-CoA. Peroxisomes also contain carnitine acyltransferases and a beta-oxidation enzyme system. This system is particularly active in the shortening of very long chain fatty acids. The carnitine acyltransferases of the peroxisomes presumably are active in the transfer of the shortened acyl-CoAs and the acetyl-CoA to the mitochondria for complete oxidation. The carnitine acyltransferases of the mitochondria can catalyse the formation of propionylcarnitine and branched chain acylcarnitines from branched chain amino acids, and methylthiopropionylcarnitine from methionine. Their formation may represent a "security valve" preventing acyl-CoA accumulation in the mitochondria. The liver, which normally releases carnitine for other tissues, releases the branched chain acylcarnitines even more easily. This may be important for the development of secondary carnitine deficiency in some inborn errors of metabolism which are accompanied by the accumulation of acyl-CoAs in the tissue. PMID- 2199595 TI - The role of the kidney in carnitine metabolism. AB - The kidney plays a major role in carnitine biosynthesis, excretion and acylation. Unlike in the rat, human kidney contains all enzymes needed to form carnitine from trimethyllysine in activities exceeding those of the liver. This carnitine precursor is found to be increased in plasma of patients with chronic renal failure. Free carnitine formed in the kidney as well as carnitine reabsorbed from the glomerular filtrate may be acylated in the proximal tubule. Isolated rat cortical tubule suspensions contain total carnitine concentrations of 2.85 mumols/g protein. During incubation over 60 min the acylcarnitine/carnitine ratio decreased, indicating deacylation of acylcarnitine in proximal tubules. Exogenous carnitine was acylated at a rate of 35 mumols/h.g protein. Besides pyruvate and acetate, ketone bodies stimulated the acylation rate severalfold, indicating that these substrates are a major source of acetyl-CoA for the acylation reaction. This may explain the higher acetylcarnitine/carnitine ratio found in urine under ketotic conditions. PMID- 2199596 TI - Primary carnitine deficiency. AB - Carnitine deficiency can be defined as a decrease of intracellular carnitine, leading to an accumulation of acyl-CoA esters and an inhibition of acyl-transport via the mitochondrial inner membrane. This may cause disease by the following processes. A. Inhibition of the mitochondrial oxidation of long-chain fatty acids during fasting causes heart or liver failure. The latter may cause encephalopathy by hypoketonaemia, hypoglycaemia and hyperammonaemia. B. Increased acyl-CoA esters inhibit many enzymes and carriers. Long-chain acyl-CoA affects mitochondrial oxidative phosphorylation at the adenine nucleotide carrier, and also inhibits other mitochondrial enzymes such as glutamate dehydrogenase, carnitine acetyltransferase and NAD(P) transhydrogenase. C. Accumulation of triacylglycerols in organs increases stress susceptibility by an exaggerated response to hormonal stimuli. D. Decreased mitochondrial acetyl-export lowers acetylcholine synthesis in the nervous system. Primary carnitine deficiency can be defined as a genetic defect in the transport or biosynthesis of carnitine. Until now only defects at the level of carnitine transport have been discovered. The most severe form of primary carnitine deficiency is the consequence of a lesion of the carnitine transport protein in the brush border membrane of the renal tubules. This defect causes cardiomyopathy or hepatic encephalopathy usually in combination with skeletal myopathy. In a patient with cardiomyopathy and without myopathy, we found that carnitine transport at the level of the small intestinal epithelial brush border was also inhibited. The patient was cured by carnitine supplementation. Muscle carnitine increased, but remained too low. This suggests that carnitine transport in muscle is also inhibited. Carnitine transport in fibroblasts was normal, which disagrees with literature reports for similar patients. PMID- 2199597 TI - Secondary carnitine deficiency. AB - For any given tissue the normal carnitine content is that which is necessary for an optimal rate of long-chain fatty acid oxidation. Tissues especially rich in carnitine are liver, muscle and heart. The endogenous rate of carnitine biosynthesis from lysine and methionine is not known to be influenced by fluctuations in the levels of the parent amino acids, as exemplified by hypermethioninaemic patients. Inadequate dietary supply of carnitine, leading to a deficiency, may occur in vegetarians and especially in subjects on total parenteral nutrition. Premature babies are especially at risk in this respect, and this has led to the addition of carnitine to solutions for intravenous alimentation. It has been suggested that carnitine plays an important role in the intramitochondrial regulations of coenzyme A homeostasis by expelling short-chain and medium-chain acyl groups from the mitochondrion in the form of acylcarnitines. These esters are preferentially excreted into the urine and thus result in a depletion of the body's carnitine stores. Important conditions in this respect are the inherited organic acidurias and disorders of fatty acid oxidation. Urinary acylcarnitines can be identified by indirect gas chromatographic or direct mass spectrometric methods. Patients on haemodialysis treatment will lose carnitine in the dialysis fluid, whereas excessive urinary losses of free and acetylated carnitine occur in the Fanconi syndrome. Secondary carnitine deficiency may be accompanied by a moderate degree of muscular dysfunction. Reassuringly, however, no signs of hepatic or cardiac involvement, as often seen in primary carnitine deficiency, have been observed. PMID- 2199598 TI - Ultrasound in pregnancy. PMID- 2199600 TI - Optimized urinary microscopy for assessment of bacteriuria in primary care. AB - Microscopy of wet-stained urinary sediment as an indicator of bacteriuria was evaluated in 418 consecutive primary care visits in a small community. Delivery of morning urine was encouraged and contributed to bladder incubation times of 4 or more hours in 79% of the visits; the overall culture positivity was about 80%. Bacteria or leukocytes alone or together as minimal requirements were suboptimal microscopy criteria for bacteriuria, whereas a minimum of moderate amounts of bacteria or 5 leukocytes per high-power field (x400) as a cutoff point yielded the best diagnostic accuracy. Optimization of urinary sediment microscopy in this way resulted in a desirable high sensitivity (97%) and efficacy (86%) in acutely symptomatic patients, as well as reasonably high efficacy (79%) in other patients, independent of sex or bladder incubation time. The method's simplicity and speed recommend it for use in primary care, particularly in patients with acute symptoms of urinary tract infection. PMID- 2199599 TI - Single-dose 500-mg clotrimazole vaginal tablets compared with placebo in the treatment of Candida vaginitis. AB - In a double-blind controlled clinical trial, 29 practitioners randomized 55 women with culture-proven Candida vaginitis to treatment with single-dose 500-mg clotrimazole vaginal tablets, and 40 to placebo. At a follow-up visit 7 to 10 days after treatment, Candida was present in 21 (38%) of those treated with clotrimazole and in 30 (75%) in the placebo group (P less than .05). Symptoms had improved or disappeared in 38 (69%) treated with clotrimazole, compared with 22 (55%) in the placebo group (P greater than .05). In 10 (23%) of the mycologically cured women, symptoms were unchanged or worse, whereas symptoms had improved or disappeared in 26 (51%) in whom Candida was isolated at the follow-up visit (P = .015). Questionnaires sent to the 95 women 4 weeks after the follow-up visit were returned by 62. Vaginal symptoms were reported by 50% in both groups. Further clinical trials including placebo are needed in general practice in the evaluation of the treatment of Candida vaginitis. PMID- 2199601 TI - Clinical applications of hypnotherapy. AB - Hypnosis has been used as a therapeutic tool for centuries, but only in the past 50 years have the clinical applications been delineated. As evident in the medical literature, the use of hypnosis by the medical community has increased, partly as a result of a growing awareness of hypnotherapy as an available treatment modality, and also as a result of major improvements in research methodology through strict standardization. Hypnotherapy, once considered to be limited to entertainment, has now proven useful in the treatment of a wide variety of medical illness. Two cases of the use of hypnosis are presented. In the first case, hypnosis is used to alleviate pain in a gravid patient in sickle cell crisis. In the second case, hypnosis is used for desensitization of dental phobia in a 27-year-old women. The historical, theoretical, and clinical applications of hypnosis are reviewed. PMID- 2199603 TI - Conjugative plasmid transfer from Escherichia coli to Clostridium acetobutylicum. AB - The conjugation mechanism of IncP plasmids may be employed to mobilize small non conjugative plasmids from Escherichia coli to a wide range of different organisms. This strategy has been adapted for use with the Gram-positive anaerobe, Clostridium acetobutylicum NCIB 8052. Several shuttle vectors containing replicons from pAM beta 1 (Enterococcus faecalis), pCB101 (Clostridium butyricum) or pWV01 (Streptococcus cremoris), together with the cis-acting oriT region of RK2, have been constructed, and transferred to and established in this organism. One of the vectors apparently contains a hot spot for insertion of IS1. Conjugative mobilization of plasmids from E. coli will provide a useful alternative to electroporation for effecting gene transfer to this industrially important anaerobe. PMID- 2199602 TI - Cloning and expression of an alpha-amylase gene from Streptomyces thermoviolaceus CUB74 in Escherichia coli JM107 and S. lividans TK24. AB - A gene coding for a thermostable extracellular alpha-amylase, carried by a 5.7 kb BamHI chromosomal DNA fragment isolated from Streptomyces thermoviolaceus strain CUB74, was cloned into Escherichia coli JM107 using, as a cloning vector, the high-copy-number plasmid pUC8. E. coli containing a recombinant plasmid pQR300 expressed the amylase gene and exported the enzyme into the periplasmic space and the culture medium. The amylase protein expressed by E. coli had the same molecular mass (50 kDa) as that expressed by the Streptomyces parent strain, which suggests that the enzyme is processed similarly by both strains. The amylase gene was also cloned into Streptomyces lividans TK24 using pIJ702 as vector. The enzyme was stable at 70 degrees C when CaCl2 was present. PMID- 2199604 TI - Misregulation of maltose uptake in a glucose repression defective mutant of Saccharomyces cerevisiae leads to glucose poisoning. AB - In hex2 mutants of Saccharomyces cerevisiae, which are defective in glucose repression of several enzymes, growth is inhibited if maltose is present in the medium. After adding [14C]maltose to cultures growing with ethanol, maltose metabolism was followed in both hex2 mutant and wild-type cells. The amount of radioactivity incorporated was much higher in hex2 than in wild-type cells. Most of the radioactivity in hex2 cells was located in the low molecular mass fraction. Pulse-chase experiments showed that 2 h after addition of maltose, hex2 cells hydrolysed maltose to glucose, which was partially excreted into the medium. 31P-NMR studies gave evidence that turnover of sugar phosphates was completely abolished in hex2 cells after 2 h incubation with maltose. 13C-NMR spectra confirmed these results: unlike those for the wild-type, no resonances corresponding to fermentation products (ethanol, glycerol) were found for hex2 cells, whereas there were resonances corresponding to glucose. Although maltose is taken up by proton symport, the internal pH in the hex2 mutant did not change markedly during the 5 h after adding maltose. The intracellular accumulation of glucose seems to explain the inhibition of growth by maltose, probably by means of osmotic damage and/or unspecific O-glycosylation of proteins. Neither maltose permease nor maltase was over-expressed, and so these enzymes were not the cause of glucose accumulation. Hence, the coordination of maltose uptake, hydrolysis to glucose and glycolysis of glucose is not regulated simply by the specific activity of the catabolic enzymes involved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2199605 TI - Activation of Ca2+ influx by metabolic substrates in Saccharomyces cerevisiae: role of membrane potential and cellular ATP levels. AB - Influx of Ca2+ into cells of Saccharomyces cerevisiae was measured under non steady-state conditions, which enable measurements of the initial rate of transport across plasma membranes without interference by the vacuolar Ca2+ transport system. Removal of glucose from the incubation medium led to inactivation of Ca2+ influx within 5 min. Readdition of glucose led to a transient increase in the rate of Ca2+ transport, reaching a peak after 3-5 min. A second increase was observed 60-80 min later. To examine whether the first transient activation of Ca2+ influx by glucose was mediated by membrane hyperpolarization, influx of 45Ca2+ was measured in the presence and absence of metabolic substrates (glucose, glycerol, and glucose plus antimycin A) in cells hyperpolarized to different values of membrane potential (delta psi). Logarithms of the rate of Ca2+ influx were plotted against values of delta psi. Two different slopes were obtained, depending upon whether the metabolic substrate was present or absent. Ca2+ influx in the presence of the metabolic substrates was always higher than expected by their effect on delta psi. Glycerol plus antimycin A did not affect Ca2+ influx. It was concluded that metabolized substrates activate Ca2+ influx not only by effects on delta psi but also by additional mechanism(s). Since no simple correlation between Ca2+ influx and intracellular ATP levels was observed, it was concluded that ATP levels do not affect the initial rates of Ca2+ transport across the plasma membrane of S. cerevisiae. PMID- 2199607 TI - Anorexia nervosa in 19th century America. AB - Compared with late 19th century publications in Great Britain and France, medical writers in the United States of the same era apparently had less interest in anorexia nervosa as a distinct clinical syndrome. A review of the literature of that period shows that American physicians very rarely referred to the "new" syndrome described in 1873 by Gull and Lasegue. Except for some short or oblique references, the first explicit clinical description of a case of anorexia nervosa by an American author (James Hendrie Lloyd) did not appear until 1893. The controversy about "fasting girls" and the all-dominating diagnosis of neurasthenia may explain the delay in the American interest in the new disorder. The present article documents and discusses this hitherto little known fragment in the history of medicine and psychiatry. PMID- 2199606 TI - Analysis of the proteinases of Trypanosoma brucei. AB - A method comprising enzyme separation by SDS-PAGE and subsequent use of peptidyl aminomethylcoumarins as substrates has been used to study proteinases of the protozoan parasite Trypanosoma brucei. The application of this method has allowed investigation of the substrate specificities of individual proteinases in cell lysates without the need for enzyme purification. The results show that T. brucei contains a group of cysteine proteinases, probably four in number, with substrate and inhibitor specificities similar to those of cathepsin L. A second group of proteinases, larger enzymes with significantly different substrate specificities and sensitivity to inhibitors, was also detected. Peptidyl diazomethanes inhibited the cysteine proteinases and also parasite growth, offering promise that peculiarities in the substrate specificity of trypanosomal cysteine proteinases could be exploited by compounds of this type. PMID- 2199608 TI - Annonaceous acetogenins: a review. AB - The Annonaceous acetogenins are a series of apparently polyketide-derived fatty acid derivatives that possess tetrahydrofuran rings and a methylated gamma lactone (sometimes rearranged to a methyl ketolactone) with various hydroxyl, acetoxyl, and/or ketoxyl groups along the hydrocarbon chain. They exhibit a broad range of potent biological activities (cytotoxicity, antitumor, antimalarial, antimicrobial, immunosuppressant, antifeedant, and pesticidal). The sources, isolation, chemistry, biogenesis, and biological actions of these compounds, published to date, are tabulated and discussed. Strategies for structural elucidation are reviewed, and structural revisions and refinements are suggested for some of the previously published compounds. PMID- 2199609 TI - Norman Dott's contribution to aneurysm surgery. AB - Between 1926-36 Norman Dott managed 39 patients with suspected intracranial haemorrhage. During this period he established important principles of diagnosis and developed new methods for the medical and surgical treatment of aneurysmal subarachnoid haemorrhage. Dott performed the first intracranial operation to treat an aneurysm and the first angiogram to demonstrate an intracranial aneurysm. This article reviews Dott's early experiences of aneurysmal subarachnoid haemorrhage. PMID- 2199610 TI - Geographical distribution of cases of Creutzfeldt-Jakob disease in England and Wales 1970-84. AB - Two hundred and sixty seven patients with a definite or probable diagnosis of Creutzfeldt-Jakob disease (CJD) were identified in an attempt to ascertain all cases of the disease in England and Wales in the period 1970-84. No evidence of space-time clustering of dates and places of onset was found for these cases. Two age- and sex-matched controls were selected for 72 of the 122 cases diagnosed in the period 1980-84 and life histories of places of residence were obtained for these cases and the controls. No evidence was found that cases had lived closer to each other than had controls at any time in their lives, except that there was an excess of cases born in London. The study does not provide supportive evidence for case-to-case transmission of CJD being an important component in the aetiology of the disease. PMID- 2199611 TI - Cerebral radiation necrosis complicating stereotactic radiosurgery for arteriovenous malformation. AB - A patient presented with symptoms and signs of raised intracranial pressure and increasing focal deficit 13 months after stereotactic radiosurgical treatment of an arteriovenous malformation (AVM). Computed Tomography (CT) showed a mass lesion at the site of the previous abnormality typical of radiation necrosis, but with features identical to those of a malignant neoplasm. Biopsy confirmed cerebral radiation necrosis. The radiation dose was 25 Gray to the periphery of two overlapping 14 mm collimator fields, delivered in a single dose. Treatment with steroids led to improvement in the symptoms and signs of raised intracranial pressure, but not the focal deficit. Radiation necrosis is a consequence of the large doses required to obliterate AVMs and is a limiting factor in their treatment. It is important for clinicians referring patients for stereotactic radiosurgery to be aware of this complication, and to be able to recognise and treat it. PMID- 2199612 TI - Development of multifocal haemorrhage in a cerebral infarct during computed tomography. PMID- 2199613 TI - Immunomodulation of T cell deficiency in humans by thymic humoral factor: from crude extract to synthetic thymic humoral factor-gamma 2. PMID- 2199614 TI - Human recombinant interleukin-2 provokes infiltration of lymphocytes into myocardium and liver in rabbits. AB - Treatment with human recombinant interleukin-2 (rIL-2) is associated with multiple organ dysfunctions, including hepatic and cardiac toxicities. We present a rabbit model that may be highly suited to investigations of these organ toxicities. Rabbits were treated with rIL-2 at a dose of 3 x 10(6) Cetus units/kg/day in divided doses every 8 h for 9-11 doses. Control animals received either excipient or 5% dextrose in water. Treatment with rIL-2 resulted in hepatic and myocardial infiltration by lymphocytes and mononuclear cells. Monoclonal antibody-staining techniques revealed a high percentage of T lymphocytes. It remains to be shown whether these infiltrates are responsible for the respective organ toxicities or represent merely an epiphenomenon of rIL-2 treatment. PMID- 2199615 TI - Induction of tumor necrosis factor by macrophage colony-stimulating factor in vivo. AB - The effect of human urinary colony-stimulating factor (CSF-1) on the production of tumor necrosis factor (TNF) in vivo was assessed. Purified CSF-1 was administered i.v. to rabbits 4 days prior to injection with lipopolysaccharide (LPS). TNF in the serum prepared from rabbits bled 90 min after LPS injection was measured using cytotoxicity assays employing mouse L929 cells and antirabbit TNF monoclonal antibody. The results indicated that CSF-1 was able to induce the production of TNF in vivo and had a synergistic effect with Propionibacterium acnes. PMID- 2199616 TI - Transcutaneous PCO2 and PO2: a multicenter study of accuracy. AB - A multicenter study used 756 samples from 251 patients in 12 institutions to compare arterial (PaO2, PaCO2) with transcutaneous (PsO2, PsCO2) oxygen and carbon dioxide tensions, measured usually at 44 degrees C. Of these samples, 336 were obtained from 116 neonates, 27 from 25 children with cystic fibrosis, and 140 from 40 patients under general anesthesia. Ninety-one patients were between 4 weeks and 18 years of age, 32 were between 18 and 60 years, and 12 were over 60. The ratio of transcutaneous to arterial P(s/a)CO2 was 1.01 +/- 0.11 with PaCO2 less than 30 mm Hg, increasing to 1.04 +/- 0.08 at PaCO2 greater than 40 mm Hg. Mean bias and its standard deviation (PsCO2 - PaCO2) were + 1.3 +/- 3.9 mm Hg in the entire group, + 1.8 +/- 4.2 mm Hg in neonates (NS). Bias was + 0.2 +/- 2.7 mm Hg when PaCO2 was less than 30 mm Hg (N = 175, NS), 1.0 +/- 3.4 with 30 less than PaCO2 less than 40 (n = 329, p less than 0.001), and + 2.04 +/- 4.00 mm Hg with 40 less than PaCO2 less than 70 (n = 229, p less than 0.001). These data suggest that, using transcutaneous PCO2 monitors with inbuilt temperature correction of 4.5%/degrees C, the skin metabolic offset should be set to 6 mm Hg. The linear regression was PsCO2 = 1.052(PaCO2) - 0.56, Sy.x = 3.92, R = 0.929 (n = 756); and PsCO2 = 1.09(PaCO2) - 1.57, Sy.x = 4.17, R = 0.928 in neonates (n = 336).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2199617 TI - Small differences, big implications. PMID- 2199618 TI - Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node positive, estrogen receptor-positive breast cancer patients: results of a multicentric Italian study. Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group. AB - Between November 1, 1983 and June 30, 1987, 510 node-positive, estrogen receptor (ER)-positive breast cancer patients have been randomly allocated to receive either chemotherapy (six intravenous [IV] cyclophosphamide, methotrexate, and fluorouracil [CMF] courses followed by four IV epirubicin courses) or 5 years of tamoxifen treatment or a combination of both therapies. After a median follow-up of 40 months, patients receiving the combined treatment achieved the best results, and those treated with chemotherapy alone achieved the worst, the difference being particularly evident in postmenopausal women. However, while the concurrent use of chemotherapy and tamoxifen did improve the results achieved by chemotherapy alone, particularly in postmenopausal women and in those with four or more involved nodes, it did not significantly improve the results achieved by tamoxifen alone, particularly in patients with higher ER tumor concentrations. Side effects were more numerous and more severe in patients receiving chemotherapy (with or without tamoxifen). Our findings, although still preliminary, confirm that tamoxifen should be the treatment of choice for postmenopausal breast cancer patients with node-positive, ER-positive tumors. In addition, the findings suggest that tamoxifen may represent a safe alternative to chemotherapy (at least to the cytotoxic regimen we used) for younger women, provided they have ER-positive tumors. In patients with ER-positive tumors, the addition of chemotherapy to tamoxifen does not seem to improve significantly the effectiveness of tamoxifen alone. PMID- 2199619 TI - Weight change in women treated with adjuvant therapy or observed following mastectomy for node-positive breast cancer. AB - Six hundred forty-six women with node-positive breast cancer from two prospective, randomized, adjuvant breast cancer trials were evaluated for changes in weight during and after receiving 60 weeks of chemotherapy, chemohormonal therapy, or observation. The median weight change in the 545 patients remaining on protocol at 60 weeks for observed postmenopausal patients was +1.8 kg, for treated postmenopausal patients +3.6 kg, and for treated premenopausal patients +5.9 kg (P less than .001). After a median follow-up of 6.6 years, premenopausal women who gained more than the median weight at 60 weeks had a risk of relapse 1.5 times greater (covariate P = .17) and a risk of death 1.6 times greater (covariate P = .04) than premenopausal women who had gained less than the median weight. In the postmenopausal patients, the trend for inferior relapse-free and overall survival in those who gained more than the median weight at 60 weeks was not significant (P = .05). We conclude that, relative to observation, adjuvant chemotherapy is associated with greater weight gain in node-positive, postmenopausal breast cancer patients; the amount of weight gain appears greater for premenopausal than postmenopausal women, and in premenopausal women, excessive weight gain may be associated with an increase in relapse and cancer related deaths in the selected patients who show no evidence of recurrence during 60 weeks of adjuvant chemotherapy. This last point must be interpreted with caution because of the exploratory nature of the analyses. PMID- 2199620 TI - Intraperitoneal carboplatin: favorable results in women with minimal residual ovarian cancer after cisplatin therapy. AB - From August 1985 to November 1989 we conducted a trial of intraperitoneal (IP) carboplatin including a dose-escalation design in 25 women with advanced gynecologic malignancies. All had extensive prior therapy with cisplatin (median cumulative dose, 525 mg/m2). Carboplatin was administered IP in 2 L of 1.5% dextrose with a 4-hour dwell time every 4 weeks for six cycles at a starting dose of 200 mg/m2. Patients with reduced creatinine clearance (30 to 60 cc/min) were escalated more slowly than those with high (greater than 60 cc/min) clearance. Thrombocytopenia was dose-limiting and often more severe in patients with compromised renal function; there was no local drug toxicity. The median time of follow-up is 25 months. Complete responses (CRs) were documented in six of 23 assessable patients (26%) by repeat laparotomy, and an additional 11 patients (48%) had no disease evident by noninvasive restaging. Five of the CRs and six of the patients with no clinically evident disease have relapsed from 3 to 40 months after therapy. Six patients (26%) are alive and free of disease 8 to 47 (median, 20) months after therapy. IP carboplatin is effective against relapsed ovarian cancer, even after prior cisplatin therapy. PMID- 2199621 TI - Chemo-radiotherapy in patients with locally advanced nasopharyngeal carcinoma: a radiation therapy oncology group study. AB - The results of radiotherapy alone for patients with locally advanced (stage III or IV) nasopharyngeal cancer (NPC) are poor in spite of the initial complete clearance. Twenty-seven patients (26 stage IV) were treated with concurrent standard radiotherapy and cisplatin 100 mg/m2 intravenously on day 1 and every 3 weeks for three courses. In 24 (89%) patients, complete response (CR) was achieved. The CR rate was higher for poorly undifferentiated cancer (100%). The major side effects were leukopenia (97%), anemia (54%), nausea and vomiting (81%), stomatitis (92%), and renal impairment (52%). Most of these side effects were either mild or moderate and reversible. All patients finished the radiotherapy dose (greater than 6,450 cGy), 19 (70%) had three courses of cisplatin, and eight had only two courses, six due to drug toxicity. Twenty-six patients with stage IV disease were compared with 78 patients treated with radiotherapy alone by the Radiation Therapy Oncology Group (RTOG). The disease free survival (DFS), overall survival, and the incidence of distant organ metastasis appear to be better in the combined group. It was concluded that the combination of chemo-radiotherapy in patients with locally advanced NPC needs to be evaluated in a phase III randomized trial. PMID- 2199622 TI - A randomized trial comparing adjuvant fluorouracil, doxorubicin, and mitomycin with no treatment in operable gastric cancer. International Collaborative Cancer Group. AB - Three hundred fifteen patients with operable gastric cancer were randomized to receive fluorouracil, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and mitomycin (FAM) or no adjuvant treatment between September 1981 and July 1984. After excluding ineligible patients, 281 patients are included in this analysis. Treatment was moderately well tolerated by the majority of patients, the common side effects being nausea and vomiting (58%) and alopecia (57%). Three possible treatment-related deaths were seen, all due to cardiac failure. At median follow-up of 68 months, 164 patients have died, 73 in the treated arm and 91 in the control arm. There was no significant difference in disease-free or overall survival between the two arms of the study (P = 0.21). There is some evidence that patients with more advanced carcinoma (T3-T4) derived some benefit from treatment (P = 0.04). The interpretation of this finding must take into account that all subgroups were defined retrospectively, and this could, therefore, be a chance finding. We conclude that adjuvant chemotherapy as given in this trial is not indicated as routine treatment in operable gastric cancer, but that further evaluation in stage T3-T4 patients is warranted. PMID- 2199623 TI - Large-cell lymphomas: clinical and prognostic features. AB - We reviewed the clinical and pathologic features in 186 patients with large-cell lymphomas seen at Vanderbilt University Hospital between 1970 and 1986. Ninety two cases (49%) were large noncleaved-cell lymphoma (LNCCL), 61 cases (33%) were large-cleaved-cell lymphoma (LCCL), 17 cases (9%) were peripheral T-cell lymphoma (PTCL), and 16 cases (9%) were immunoblastic sarcoma of B cells (IBS-B). These subsets of large-cell lymphoma did not differ with respect to median age, distribution by stage, or incidence of bone marrow involvement. Significant differences between groups were noted with regard to male:female ratio, incidence of symptoms, incidence of extranodal disease, and pattern of adenopathy. However, when LCCL was excluded from the analysis, none of these differences were significant. By univariate analysis, age, stage, marrow involvement, extranodal disease, B symptoms, elevated serum lactic dehydrogenase (LDH), and diffuse pattern were unfavorable prognostic features in large-cell lymphoma. However, when cases were stratified by cell of origin, nodular versus diffuse pattern was of no prognostic significance. Nodularity was favorable only because 71% of nodular and nodular-diffuse cases were LCCL, while the majority of diffuse cases were LNCCL. Although IBS-B is considered a "high-grade" lymphoma, we found no evidence for inferior survival in these patients compared with LNCCL or LCCL. In fact, survival was better in IBS-B than in LNCCL or LCCL, although this difference was not significant. However, survival was significantly inferior in PTCL (median, 11 months) compared with the other subsets of large-cell lymphoma (median, 46 months; P = .038, log-rank test). Since the association of PTCL and an inferior survival has most often been noted in the context of "second generation" chemotherapy, we believe that this association may be therapy dependent and may be minimized by the use of more aggressive chemotherapy regimens. PMID- 2199624 TI - Phase II trial of Serratia marcescens extract in recurrent malignant astrocytoma. AB - Nineteen assessable patients with recurrent malignant astrocytomas who had failed standard therapy (surgery, radiation, and/or chemotherapy) were treated on a phase I-II trial with a biologic extract of Serratia marcescens (ImuVert; Cell Technology, Boulder, CO) a new biologic response modifier (BRM). Two complete responses (CRs) were seen, of 63 and 77+ weeks duration. One minor response (MR) occurred, of 6 weeks duration. There were four additional stable (S) patients, with durations of 58+, 39, 12, and 7 weeks. Median time to progression and median survival in the CR plus MR patients were 63 and 129+ weeks, respectively. Overall, median time to progression and median survival were 12 and 19 weeks, respectively. Three patients are alive greater than or equal to 2.5 years from study entry. Common toxicities included transient (less than 72 hours) tenderness, induration, and erythema at the injection sites. Systemic toxicities were less frequent and included fever, chills, nausea/vomiting, headache, arthralgia, and hypotension. The response rate (CR plus MR) to this new BRM is modest (16%). However, the observation of CRs in patients with advanced recurrent malignant astrocytomas, with acceptable overall toxicity, warrants further study of this agent. PMID- 2199625 TI - Susceptibility of Eikenella corrodens to antimicrobial agents. AB - Twelve Eikenella corrodens strains were isolated from dental infections and tested for their susceptibility to antimicrobial agents by an agar dilution method. All strains were susceptible to penicillin, ampicillin and tetracycline, and resistant to cephalexin and metronidazole and moderately resistant to erythromycin, gentamicin and cefaclor. PMID- 2199626 TI - The effect of fresh human serum on ofloxacin bactericidal activity. AB - We have studied the possibility of an increase in ofloxacin bactericidal activity when it is combined with fresh human serum. The tested strains were 10 clinical isolates of Klebsiella pneumoniae. From among our strains 5 were susceptible to serum bactericidal activity and 5 were found to be resistant. We selected two serum concentrations (15 and 35%) to test against susceptible strains and two (55 and 75%) to test against resistant strains in combination with the minimum inhibitory concentration (MIC), 1/2MIC and 1/4MIC of ofloxacin. The results show a slight variability among the tested strains depending on microbiological characteristics of single strains, however, the serum + ofloxacin combination was advantageous. Only one exception was observed: a resistant strain that had an increased survival percentage against ofloxacin and serum in combination. PMID- 2199627 TI - Pharmacokinetics and tissue distribution of amoxicillin plus clavulanic acid after oral administration in man. AB - Augmentin (875 amoxicillin and 125 mg potassium clavulanate) was administered orally to patients with chronic bronchitis. Concentrations of amoxicillin and clavulanic acid were measured in serum, sputum and urine. Peak serum levels for amoxicillin of 11.23 +/- 2.61 micrograms/ml were observed at 2 hours and for clavulanic acid of 2.55 +/- 0.54 micrograms/ml at 1 hour. After 9 hours, 50% of the amoxicillin and 39% of the clavulanic acid had been renally excreted. The peak sputum concentration of amoxicillin was 1.31 +/- 0.42 micrograms/ml at 4 hours and of clavulanate was 0.79 +/- 0.23 micrograms/ml at 2 hours. Patients awaiting surgery received an oral dose of augmentin as above. Samples of lung, tonsil, middle ear mucosa and prostate were obtained and tissue concentrations of both compounds measured. Peak levels of amoxicillin ranged from 0.87 micrograms/g (tonsil) to 2.56 micrograms/g (lung) and of clavulanic acid from 0.20 micrograms/g (prostate) to 0.56 micrograms/g (lung) between 3 and 4 hours after dosing. PMID- 2199628 TI - A single dose of aztreonam in the prevention of urinary tract infections in elderly catheterized patients. AB - We have compared the effects of aztreonam and placebo in the prevention of urinary tract infections (UTI) in elderly hospitalized patients who needed urethral catheterization. 162 patients (96 males, 66 females; age range 60-91 years) were randomly allocated to receive double-blind a single dose of aztreonam (2 g i.m. 80 patients) or placebo (4 ml lidocaine 2%, 82 patients) three hours before catheterization. All patients were followed-up for 7 days. Urine culture was performed before, at the first, third and seventh day of catheterization. At the end of follow-up 71/80 patients (88.7%) who received a single preventing dose of aztreonam had negative urine culture without clinical signs of UTI. On the contrary, in the group treated with placebo at the end of follow-up only 38/82 patients (46.3%) had negative urine without clinical signs of UTI. In conclusion, our data suggest that a single 2g i.m. dose of aztreonam is effective in preventing UTI in elderly patients needing indwelling urethral catheterization. PMID- 2199629 TI - Pefloxacin in the antibacterial treatment of immunodepressed patients. AB - Pefloxacin 800 to 1200 mg daily was given for 3 to 20 days, orally or intravenously, to 84 immunocompromised patients. Five patients dropped out because of side effects and 2 for other causes. Treatment efficacy was evaluated in 77 patients, 43 men and 34 women, aged 18 to 80 years. Immunodepression resulted from malignancy in 46 patients, LAS/ARC or AIDS in 28, and from unknown causes in 3. Fifty-eight patients had documented infections (respiratory-tract infections 29, urinary-tract infections 13, septicemia 10, other 6) and 19 had a fever of unknown origin (FUO). Cure or significant improvement of symptoms was achieved in 81% of patients with documented infections and in 74% of patients with FUO. Side effects (mainly gastrointestinal disturbances and skin rash) occurred in 7 patients (8.2%), including dropouts. These results suggest that pefloxacin may be useful for the antibacterial treatment of immunodepressed patients. PMID- 2199631 TI - The committee meeting alternative. Using the Delphi technique. AB - Decision making is an important component of the role of nursing administrators; yet, committee meetings for decision making have limitations. The author describes the characteristics of the Delphi technique and compares the Delphi process to the face-to-face discussions occurring in committee meetings. Specific information about the use of the Delphi technique as well as examples of its use are presented. PMID- 2199630 TI - Strategic decision making. AB - A key management function is making strategic decisions when there is competition for scarce resources. The authors report an in-depth study of decision making and the choices made by nurse executives when acquiring, distributing, and redistributing funds, information, space, and personnel. They describe successful strategies for resource allocation and present a model for analyzing strategic decisions. PMID- 2199632 TI - JONA's Semiannual Directory of Consultants to Nursing Administration. PMID- 2199633 TI - Bernard S. Schweigert (1921-1989). PMID- 2199634 TI - Endogenous zinc excretion in relation to various levels of dietary zinc intake in the mink (Mustela vison). AB - Endogenous zinc excretion was studied in adult male mink fed experimental diets for 73 d, including a collection period from d 69 to 73. Dietary zinc levels were 2.8, 26 or 121 mg/kg wet weight. In accordance with the results of a methodological study, also reported here, the animals had an intramuscular injection of 65ZnCl2 12 d before the start of the collection period. Total fecal (endogenous + unabsorbed) zinc excretion for d 69-73 in the three groups was 2.3, 20.4 and 91.0 mg. The endogenous zinc excretion was 1.3, 2.0 and 6.4 mg, corresponding to 80.8, 10.6 and 6.4% of the zinc intake. Thus, the endogenous excretion was mainly important for the zinc homeostasis at low zinc intake, whereas at high intake the homeostasis was regulated via absorption from the digestive tract. The overall conclusion of the experiment was that mink are comparable to other species (including man) in regard to mechanisms controlling zinc homeostasis. PMID- 2199635 TI - Iron deficiency: improved exercise performance within 15 hours of iron treatment in rats. AB - We tested the hypothesis that a very rapid improvement in exercise performance of iron-deficient rats after treatment with iron might reveal a rate-limiting role of ionic iron as an enzyme cofactor in energy metabolism. Rats were given iron deficient or control diets after weaning at 21 d of age and intraperitoneal iron dextran (50 mg/kg) at 45 d of age. Time to fatigue during an easy walking exercise (endurance) was measured 15 and 18 h after iron dextran or saline injection. Endurance increased more than threefold compared to the saline treated, iron-deficient animals without a significant change in hemoglobin concentration. This prompt improvement suggests that lack of cofactor iron might play a metabolically important role in impairing exercise performance in the severely iron-deficient rat. PMID- 2199636 TI - Hunger and undernutrition in the United States. AB - In the United States, where food is plentiful nationwide, detection of populations at risk of hunger and malnutrition must rely more on social and economic indicators than on physiological indices, important as these are. Large federal programs expanded or created after the 1969 White House Conference on Food, Nutrition, and Health were shown to be successful during the 1970s in reducing hunger and malnutrition as a massive social phenomenon, even though poverty conditions remained the same. Studies that apply our knowledge of nutritional and dietary requirements to construct a "market basket" of inexpensive, commonly used foods that meet the Recommended Dietary Allowances (RDA) and that set estimated minimum incomes as a multiple of the cost of such an "RDA-based market basket" plus the costs of other necessities would identify populations and families at risk and permit better targeting of food programs. PMID- 2199637 TI - Functional indicators and outcomes of undernutrition. AB - The advantages and limitations of using functional methods are discussed in the context of identifying undernutrition and hunger in children in the United States. At this time many of these methods have been used only in developing countries where undernutrition is more serious. However, there is great need to investigate whether, when and how undernutrition in the United States affects children's development. Functional measures can detect undernutrition and hunger in some situations where biochemical or clinical measures cannot. PMID- 2199638 TI - Defining undernutrition for public health purposes in the United States. AB - Lack of consistency among definitions of undernutrition used for different public health purposes in the United States hinders an effective diagnosis of the problem and the design of interventions to prevent and treat undernutrition. No single-case definition of undernutrition is appropriate for all purposes. These purposes include surveillance of the prevalence of undernutrition in the population, epidemiological research on risk factors and consequences of undernutrition within population subgroups and communities, and screening, monitoring and evaluation of nutritional programs. We recommend that a cut-off of -2.0 SD (2.3 percentile) for weight-for-age, height-for-age, and weight-for height on National Center for Health Statistics (NCHS) reference growth charts be used to estimate and monitor the prevalence of undernutrition in the United States, in accordance with guidelines of the World Health Organization. Epidemiological research on population-based risk factors for undernutrition and its functional consequences is required to identify the appropriate nutritional indicator and cut-off for screening and monitoring and evaluation of interventions. PMID- 2199639 TI - Occupational reproductive risks: sources, surveillance, and testing. PMID- 2199640 TI - Is immunohistochemical analysis of oestrogen and progesterone receptors in endometrial carcinoma superior to the radioligand binding assay? AB - The aim of this study was to evaluate tissue and steroid receptor heterogeneity in endometrial carcinoma specimens as a possible source of discordance between biochemically assayed receptor status and response to endocrine treatment. For this purpose the oestrogen receptor (OR) and progesterone receptor (PR) levels in specimens from 16 endometrial carcinoma patients were analysed on adjacent tissue sections using both a radiochemical and an immunohistochemical assay. With immunohistochemical receptor analysis extensive tissue and tumour cell receptor heterogeneity was observed. Many tumour samples revealed up to 75 per cent contamination with benign tissue. In the majority of cases, evaluation of immunoreactivity in normal tissue elements of the specimen could explain the apparent discordance between semiquantitative immunohistochemical receptor scoring of tumour cells and radiochemical receptor assay. Immunohistochemical analysis of OR and PR in endometrial carcinoma specimens allows a more specific determination of tumour cell receptor content and hence may yield a more accurate prediction of response to endocrine therapy than the biochemical assay. PMID- 2199641 TI - Ki-ras oncogene mutations in non-HPV-associated anal carcinoma. AB - Human papillomavirus 16 (HPV 16) DNA is found in a high proportion of anal squamous cell carcinomas in whose genesis it is thought to play an important role. In addition, it can be shown to cooperate in vitro with activated ras oncogenes in cellular transformation. We have therefore screened a series of such tumours for activating mutations of the ras oncogene family using DNA amplified in vitro by the polymerase chain reaction (PCR) and a series of synthetic oligonucleotide probes. Mutations were seen in only two cases (both Ki-ras codon 12), neither of which was HPV-associated. Our results suggest that ras activation is not a common event in the genesis of these tumours and, when it does occur, it does not appear to cooperate with HPV. PMID- 2199642 TI - Early postnatal dexamethasone therapy in premature infants with severe respiratory distress syndrome: a double-blind, controlled study. AB - To determine whether early (less than or equal to 12 hours) postnatal dexamethasone therapy would facilitate removal of the endotracheal tube and improve outcome in premature infants with severe respiratory distress syndrome, we conducted a double-blind, controlled study of 57 infants whose birth weights were less than 2000 gm. The placebo (n = 29) and treated (n = 28) groups were comparable in birth weight (mean +/- SD: 1273 +/- 323 vs 1318 +/- 359 gm), gestational age (30.1 +/- 2.1 vs 30.8 +/- 2.7 weeks), postnatal age (8.7 +/- 3.1 vs 8.5 +/- 3.1 hours), and pulmonary function at the start of the study. The dose of dexamethasone was 1.0 mg/kg/day for 3 days and then was progressively decreased for 12 days. Infants in the dexamethasone group had significantly higher pulmonary compliance, tidal volume, and minute ventilation, and required lower mean airway pressure for ventilation than infants in the placebo group. The endotracheal tube was successfully removed from more infants in the dexamethasone group (16/28 vs 8/29; p less than 0.025). Nineteen infants (65%) in the placebo group and 11 (39%) in the dexamethasone group (p less than 0.05) had lung injuries. Dexamethasone therapy was associated with a temporary increase in blood pressure and plasma glucose concentration and a delay in somatic growth. We conclude that early postnatal dexamethasone therapy improves pulmonary status, facilitates removal of the endotracheal tube, and minimizes lung injuries in premature infants with severe respiratory distress syndrome. PMID- 2199643 TI - Effect of lactose on mineral absorption in preterm infants. AB - To determine whether a reduction of dietary lactose affects mineral absorption in preterm infants, a controlled, randomized, 72-hour balance study was conducted with very low birth weight infants (birth weights less than 1400 gm) fed Similac Special Care formula with a 50:50 carbohydrate blend of glucose polymers and lactose (n = 8) or a nearly identical formula with 100% carbohydrate as lactose (n = 10). The studies were conducted after at least 3 consecutive days of full oral feeds at a mean age of approximately 23 days. There was no difference between groups in percentage of apparent absorption of calcium, phosphorus, magnesium, zinc, copper, or manganese. Retention of these nutrients was similar to or greater than that which occurs in utero. Calcium absorption was 75% of intake. These results indicate that reducing the lactose content of premature infant formulas to 50% of the carbohydrate does not impair mineral absorption. PMID- 2199644 TI - Growth patterns of low birth weight preterm infants: a longitudinal analysis of a large, varied sample. AB - To obtain growth data on a large sample of low birth weight preterm infants, we monitored 608 infants longitudinally in an eight-site collaborative program. Ninety-nine infants weighed less than or equal to 1250 gm at birth, 289 between 1250 and 2000 gm, and 220 infants between 2000 and 2500 gm. Thirty-four percent were white, 52% black, and 14% Hispanic. Weight, height, and head circumference were measured at birth and at 40 weeks and 4, 8, and 12 months of gestation corrected age on at least 553 infants each time. Descriptive statistics for all growth variables and a body mass index (kilograms per square meter), plotted by sex and birth weight group, demonstrated growth patterns lower than published standards for term infants of the same age and sex. These patterns of growth differed by birth weight group. No catch-up growth was noted by the 12-month examination (gestation-corrected age) for any birth weight group. We conclude that low birth weight preterm infants have different patterns of growth than term infants during the first year of life, even with plotting corrected for gestational age. PMID- 2199645 TI - Age-adjusted thyrotropin criteria for neonatal screening for hypothyroidism. PMID- 2199646 TI - Hypoglycemia in children with insulin-dependent diabetes mellitus. PMID- 2199647 TI - Infant nutrient supplementation. AB - This review addresses vitamin and mineral supplementation recommendations, practices and rationales, patterns of supplement use, and the relationship between supplementation and nutrient concerns for older infants. According to current recommendations, healthy infants do not need supplements if vitamin D fortified milk is used, the diet includes adequate vitamin C, and iron-fortified cereals or formula are used. Infants fed human milk exclusively may need vitamin D supplements. Nevertheless, approximately one third to one half of 6- to 12 month-old U.S. infants receive nutrient supplements, as liquid vitamin A, D, and C preparations or multivitamin preparations, with or without iron or fluoride. Recent surveys suggest that most infants have more than adequate vitamin and mineral intakes, with the possible exception of iron. The risk of poor vitamin A status is less likely than the risk of poor water-soluble-vitamin or iron status in the United States. Possibly marginal intakes of zinc and copper (not in currently available infant supplements) suggest the need for further research. Research, infant supplement formulation reevaluation, and education are suggested so that nutrient supplements for prophylaxis can be used most effectively and appropriately. PMID- 2199648 TI - Mineral and vitamin D adequacy in infants fed human milk or formula between 6 and 12 months of age. AB - During the latter half of an infant's first year, adequate mineral and vitamin D intakes may be important not only for the prevention of rickets but also for the attainment of optimal adult peak bone mass. Ingestion of 400 IU vitamin D per day, either as a supplement or contained in formula or table milk, will result in normal serum concentrations of vitamin D,25-hydroxyvitamin D, and 1,25 dihydroxyvitamin D. Human milk from a vitamin D-sufficient mother provides a marginal amount, less than 100 IU/L/day of total vitamin D activity from the vitamin D and 25-hydroxyvitamin D. Infants exclusively fed human milk of vitamin D-deficient mothers, who do not receive additional vitamin D or adequate exposure to sunlight, are at significant risk for vitamin D-deficiency rickets. The low concentration of phosphorus in human milk is adequate for most term infants but probably compounds any vitamin D deficiency. Intake of phosphorus from formula or table milk is more than adequate, and the addition of baby foods increases this mineral's intake to generous levels. Calcium is well absorbed and adequate in human milk if vitamin D is sufficient, but concern exists about calcium intake from infant formulas for this older group. My colleagues and I have conducted studies of bone mineral content and mineral homeostasis in term infants fed human milk (300 mg/L calcium), standard cow milk formula (440/mg/L calcium), or a soybean formula (600 mg/L calcium); our findings suggest that all three types of feedings provided comparable bone mineralization and normal indicators of mineral homeostasis. Mean calcium retentions at 6 months, 9 months, and 12 months in all three groups were between 138 and 205 mg/day, substantially more than the 130 mg/day estimated to be needed from body composition data. Estimates for phosphorus were similarly generous. The questions of whether higher calcium intakes will result in further increases in bone mineral content and of the effect of beikost on calcium absorption from different milks require further study. PMID- 2199649 TI - Iron needs during rapid growth and mental development. AB - Growth and behavioral development during infancy is highly dependent on a bioavailable source of dietary iron. This brief review examines the extent of iron deficiency anemia in the United States in the late 1980s, the daily dietary intake of iron, and the impact of iron deficiency on growth and on mental and psychomotor development. It is incumbent on physicians and other health care professionals caring for infants to direct infant feeding toward the prevention of nutritional iron deficiency. PMID- 2199650 TI - Trace minerals in the nutrition of children. AB - Trace elements perform important functions in growth and development. However, little information exists about their dietary requirements during the demanding period of infancy. Opportunities to add to knowledge of the physiologic significance and dietary adequacy of trace elements in human nutrition are provided by recent analytic advances. Specific, sensitive, and reliable methods for the detection of trace element imbalances are sorely needed. Although several factors influence the dietary needs of these essential elements, the basis for establishing dietary needs in infants is hindered by the death of studies that have assessed their bioavailability in this age group. Thus until it has been conclusively shown otherwise, the physiologic response to human milk is used as the standard for infant feeding practices. This review is limited primarily to the physiologic significance and bioavailability of zinc, copper, manganese, molybdenum, chromium, fluoride, and selenium. The space devoted to each trace element is not meant to represent the element's importance but, rather, to reflect some of the present understanding of its metabolism and utilization. PMID- 2199651 TI - The feeding relationship: problems and interventions. AB - The feeding relationship is the complex of interactions that take place between parent and child as they engage in food selection, ingestion, and regulation behaviors. Effective feeding supports a child's developmental tasks of homeostasis, attachment, and separation. Feeding of the newborn infant is most successful when parents allow the infant to determine timing, amount, preference, pacing, and eating capability. During the attachment phase, such infant controlled behaviors allow parents to engage affectively with the child. Successful regulation of state and attachment provides the groundwork for the separation-individuation phase. In feeding, effective parents provide opportunities to explore but also provide structure and limits. Feeding and growth problems often stem from distorted dynamics around feeding, which can be indicative of distorted parent-child interactions. Incidence estimates range from 1% to 2% for severe and prolonged problems to 25% to 35% for common difficulties such as food refusal and "overeating." An evaluation of feeding dynamics should always be made as part of the diagnostic study of a child who is eating or growing inappropriately. To prevent problems in feeding, practitioners may teach and support positive feeding dynamics as part of primary care, refer parents for instruction in positive approaches to feeding, and detect and refer attitudinal and behavioral problems early. PMID- 2199652 TI - Reduction in cell entry of Eimeria tenella (Coccidia) sporozoites by protease inhibitors, and partial characterization of proteolytic activity associated with intact sporozoites and merozoites. AB - The role of proteases in the invasion of host cells by Eimeria tenella (Wisconsin strain) was studied in vitro. Protease inhibitors were used to treat sporozoites before inoculation or were applied to cultured chicken kidney cells before infection. The inhibitors antipain, leupeptin, aprotinin, L-1-tosylamide-2-phenyl ethyl chloromethyl ketone (TPCK), or N-alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK) reduced parasite invasion to 16-66% of control after treatment of cultured cells or sporozoites with 5- or 50-micrograms/ml concentrations of inhibitors in the culture medium. Phenylmethylsulfonyl fluoride (PMSF) reduced invasion to 32 57.7% at concentrations of 1-4 mM. The optimum pH for hydrolysis of azocasein by intact sporozoites or merozoites was determined over a range of pH 5.0 to pH 9.0. Sporozoites were highly active over a broad range from pH 5.5 to pH 9.0, with an apparent optimum at pH 8.0. Merozoites had a much lower specific activity with pH optima at 7.0 and 8.5. The protease activity of sporozoites or merozoites could be inhibited completely by the addition of 50 micrograms/ml of leupeptin, TPCK, or TLCK or of 4 mM PMSF. Antipain inhibited proteases of sporozoites but not of merozoites. Pepstatin had little effect on either sporozoites or merozoites. The results suggest that parasite proteases of Eimeria may be necessary for invasion of host cells. PMID- 2199653 TI - Inhibition of leukocyte function by serum from patients with trichinellosis. AB - Modification of leukocytic function has been reported in only a few human parasitic diseases. In this study we evaluated the effects of the sera from patients infected with Trichinella on chemotactic and phagocytic responses in leukocytes. Leukocyte chemotaxis was tested by the agarose method and phagocytosis by the technique of Yamamura, modified for Saccharomyces cerevisiae. Sera were acquired from patients during a trichinellosis outbreak that occurred in northern Italy in 1986. The parasite was isolated from 1 patient and isoenzymatically typed as Trichinella sp. 3, a new taxon, previously considered Trichinella nelsoni. The results indicated that sera from Trichinella-infected humans inhibited both chemotaxis and phagocytic responses in leukocytes. These findings suggest the existence of serum factor(s) in trichinellosis patients that modify host leukocytic functions. The source and nature of active serum components and the mechanism by which they modulate leukocyte function remain to be clarified. PMID- 2199654 TI - Localization of a 24-kilodalton glycoprotein in adult Schistosoma mansoni using immunofluorescence and immunoelectron microscopy. AB - Studies on schistosome protective immune responses have focused mainly on antigens of the parasite's syncytial surface. One of the characterized schistosome antigens, a 24-kDa glycoprotein, has been considered important in mechanisms of immune evasion by the parasites. In the present study, using affinity-purified antibodies to the 24-kDa protein for immunofluorescence and immunoelectron microscopy, we demonstrated an association of the 24-kDa antigen with the discoid bodies (the major syncytial inclusion bodies; DBs) and the surface membrane complex (most likely the apical plasma membrane) of adult Schistosoma mansoni. This is consistent with previous observations that the 24 kDa antigen appeared to be localized to the syncytial membrane and DB fractions. The present results also support the suggestion that the DBs are the precursor organelles of the apical plasma membrane. PMID- 2199655 TI - Social consequences of pediatric conditions: fertile area for future investigation and intervention. AB - Very little systematic research has examined the peer relations and social functioning of youngsters with chronic illness. In order to stimulate empirical and clinical interest in this potentially important area of pediatric psychology, the present paper discusses several pertinent tissues. These include (a) the role of peers in disease adaptation and treatment management, (b) specific aspects of diseases or treatments that are likely to have implications for youngsters' social functioning, (c) guidelines for further investigation in this area, and (d) suggestions for incorporating peer/social issues into educational programs and intervention efforts for youngsters with chronic disease. Throughout the discussion, the complex interplay between peer relations and adaptation to chronic illness is highlighted. PMID- 2199656 TI - Variation in lipid and sterol contents in Candida albicans white and opaque phenotypes. AB - In the white-opaque transition, cells of Candida albicans strain WO-1 switch reversibly and at high frequency between phases which differ both in colony and cellular phenotype. The lipid and sterol contents of the two phases were compared. White cells were higher in lipid and sterol contents in both mid exponential and stationary phase cultures. In mid-exponential phase cultures, the lipids of white cells accumulated substantial amounts of apolar compounds, including steryl esters, alkyl esters, triacylglycerols, fatty acids, free sterols and mono- and di-glycerides, while opaque cells accumulated nearly equal proportions of apolar and and polar compounds, mainly phosphatidylethanolamines and phosphatidylcholines. In stationary phase cultures, both white and opaque cells had slightly higher proportions of polar lipids. Major differences in the lipid composition between white and opaque cells involved the contents of free sterols and derivatives of sterols. White cells contained higher proportions of free sterols than opaque cells, while opaque cells contained more steryl glycosides and steryl esters (approximately 2.5 times higher). Comparison of the sterols of the white and opaque cells by UV, TLC and GLC showed that a qualitative as well as quantitative difference exists between the two phenotypes. Fatty acid analysis of white and opaque cells showed that C-16 and C-18 fatty acids are the most abundant in both phenotypes. White and opaque cells varied in their fatty acid composition. The former had higher proportions of palmitoleic (16:1) and stearic (18:0) but lower proportions of linoleic (18:2) fatty acids than opaque cells. Analysis of fatty acids of major lipid classes present in both forms showed that fatty acid pattern varied dramatically according to whether the class had been isolated from white or opaque cells. Our results suggest that the lipid composition (particularly sterol and polyunsaturated fatty acids) of the opaque phenotype resembles that of mycelial cultures. Opaque cells showed more resistance to amphotericin B, nystatin, 5-fluorocytosine (flucytosine) and miconazole nitrate than white cells. PMID- 2199657 TI - Experimental pathogenicity and acid proteinase secretion of vaginal isolates of Candida parapsilosis. AB - Isolates of Candida parapsilosis from women with or without candidal vaginitis were compared for their ability to produce secretory aspartate (acid) proteinase and their virulence for normal or cyclophosphamide-immunodepressed mice. Although all isolates were strongly proteolytic in vitro, only those from candidosis affected subjects were appreciably pathogenic for neutropenic mice. In these animals, organ invasion was monitored after challenge with representative isolates of each category. The number of yeast cells in the kidneys of animals infected with an isolate from a subject without candidal vaginitis was approximately one order of magnitude less than that in mice infected with either one of two isolates from patients with candidal vaginitis. Mice infected with either category of C. parapsilosis isolates developed antibodies against a mannoprotein-rich extract of the cell wall, and these antibodies did not cross react with a chemically similar preparation from Candida albicans. However, only those animals which had been challenged with one of the isolates from a candidosis subject produced a low level of antibodies, detectable by ELISA, against an acid proteinase of C. parapsilosis. These antibodies cross-reacted with a highly purified enzyme preparation of C. albicans. The data demonstrate differences in the potential virulence of different isolates of C. parapsilosis and suggest that the ability to express the acid proteinase in vivo may be related to differences in pathogenicity. PMID- 2199658 TI - Transanal mucosal sleeve resection for the treatment of rectal prolapse in children. AB - This is a report of a simple transanal operation performed on six patients (age range, 19 months to 18 years), who underwent unsuccessful nonoperative management of complete rectal prolapse for at least 1 month (range, 1 month to 13 years). All patients had normal sweat chloride levels, normal chest radiographs, and normal barium enemas. None of the patients were neurologically compromised. At the time of surgery, all but one patient had occurrence of reducible prolapse with minor straining or with every bowel movement. No severe mucosal ulcerations were present. Surgical therapy consisted of the transanal mucosal sleeve resection described herein. In this series, there were no anastomotic leaks, no clinically evident strictures and no recurrence of prolapse in 1.5- to 19-year follow-up. Surgical therapy for rectal prolapse in infants and children is rarely necessary. Various complicated or ineffective operations for the treatment of this condition have been recommended in the past. This technique offers a simple, safe, and effective method of treating complete, medically intractable rectal prolapse in children. PMID- 2199659 TI - Ultrasonography in the management of possible appendicitis in childhood. AB - One hundred thirty-four children referred to the pediatric surgical service with the diagnosis of possible acute appendicitis underwent abdominal ultrasonography within 24 hours of admission. A final diagnosis of appendicitis was made in 45, and of gynecological disease in 11 children. One child had pancreatitis, another jejunal perforation, and a third gross mesenteric lymphadenopathy. In 75 children the clinical picture completely resolved without a definitive diagnosis being made. Clinical diagnosis of gynecological disease showed two false-negatives, and three false-positives, whereas the ultrasonographic diagnosis was accurate in all patients. The sensitivity of the pediatric surgical diagnosis at the time of admission for acute appendicitis was 49% (23 false-negatives) and the specificity was 95% (three false-positives). Ultrasonographic diagnosis of appendicitis had a sensitivity of 89% (five false-negatives) and a specificity of 92% (five false positives). There was a negative laparotomy rate of 0.7% (one patient) using both clinical evaluation and ultrasonography. These data suggest that abdominal ultrasonography in the child with possible appendicitis is an important diagnostic adjunct. PMID- 2199660 TI - Internal jugular phlebectasia in two siblings: manometric and histopathologic studies of the pathogenesis. AB - Two brothers, 4 years and 6 years of age, presented with a swelling in the right side of the neck. Ultrasonography and venography confirmed a diagnosis of phlebectasia of the right internal jugular vein (IJV). In an attempt to elucidate the etiology of this rare lesion, venous pressures in both the dilated right IJV and in the left IJV were taken under general anesthesia with intratracheal intubation at the time of surgery in each patient. No significant difference in pressure elevation with increase of intrathoracic pressure by overinflating the breathing bag was observed between the right and left IJV, suggesting that there would be no mechanical obstructive process generated on exertion, in each case. Microscopic examinations of a dissected portion of the dilated IJV showed paucity of muscle layer of the vein wall in the younger patient, and absence of that in the elder. Therefore, we assume that congenital muscle defect of the right IJV wall, rather than mechanical obstruction in the lower neck or the mediastinum, might cause phlebectasia. To our knowledge, this is the first report of IJV phlebectasia in siblings. PMID- 2199661 TI - Cystic and solid heterotopic brain in the face and neck: a review and report of an unusual case. AB - An unusual case of heterotopic brain tissue was confused as a lymphangioma in the neck. Although these lesions are rare, they should be included in the differential diagnosis of congenital head and neck masses. They can compress and deform surrounding structures and cause airway obstruction in the newborn. Excision is curative, but the possibility of encephalocele should be eliminated by prior computed tomography scan. PMID- 2199662 TI - Delayed puberty in girls having biliary atresia. AB - Biliary atresia patients have several problems even after undergoing successful Kasai operation. Fourteen female patients have been followed for over 12 years after successful Kasai original portoenterostomy procedures. The oldest patient is 21 years of age. All patients are jaundice-free, but 10 patients have a history of esophageal varices and/or hypersplenism. Five patients complain of menstrual disorders. The average age of menarche was delayed 1 year, 9 months, compared with Japanese controls. Two cases of 11 (18.2%) presented primary amenorrhea after 14 years, 6 months, which is mean + 2SD of Japanese controls. Four cases of 11 (36.4%) showed secondary amenorrhea. Unestablished menstrual cycles after 2 years of menarche were observed in two patients of nine (22.2%). Four cases had regular menstruation. Five patients showed delay in the development of pubic hair and breasts. Six patients showed atypical body height velocity pattern that showed no peaking, and one patient showed no growth spurt. All the patients with amenorrhea had portal hypertension. In hormonal evaluation, the patients with menstruation showed normal or slightly good reaction of luteinizing hormone and follicle stimulating hormone in the luteinizing hormone releasing hormone test, having normal to high estradiol levels. The patients with menstrual abnormality showed overreaction of LH, having normal estradiol levels. PMID- 2199663 TI - Pediatric application of the bladder volume instrument. PMID- 2199664 TI - Multifocal intraocular lenses. AB - Current multifocal intraocular lens designs incorporate refractive or diffractive optical principles to achieve increased depth of focus. Information about four basic design concepts is presented. Early clinical results with two of these, the IOLAB Nuvue two-zone refractive multifocal and the 3M diffractive multifocal, are summarized. PMID- 2199665 TI - Astigmatic keratotomy: a review of basic concepts with case reports. AB - Despite the use of small incisions, better wound closure, and other technical improvements in cataract and corneal surgery, astigmatism remains a problem for the cataract and refractive surgeon. Case reports illustrate the applicability of astigmatic keratotomy in post-cataract and idiopathic astigmatism. The basic concepts of corneal relaxing incisions are reviewed and the frequently misunderstood coupling phenomenon is explained in the light of the "law of elastic domes." Properly used, astigmatic keratotomy with coupling effectively corrects a wide variety of types of astigmatism. PMID- 2199666 TI - Postcataract extraction ptosis: effect of the bridle suture. AB - Postcataract extraction ptosis is a common complication of cataract surgery. While many factors have been implicated in its etiology, trauma to the superior rectus/levator complex is considered the most important factor. We prospectively evaluated the effect of two superior rectus bridling techniques on the degree and severity of ptosis present three months after cataract surgery. All other potential variables were controlled for. Bridling the tendon of the superior rectus muscle using the direct, subconjunctival (open) approach results in significantly less severe ptosis than the standard technique of indirect transconjunctival (closed) bridling. PMID- 2199667 TI - Recollections of the early days of intraocular lens implantation. PMID- 2199668 TI - Suprachoroidal hemorrhage after placement of a scleral-fixated lens. AB - Six days after suture-fixation of a posterior chamber lens to the sclera, a suprachoroidal hemorrhage occurred causing pain and intraocular lens dislocation. Placing the sutures at the 3 o'clock and 9 o'clock positions and having the needles exit 2 mm posterior to the limbus may have inadvertently increased the possibility of the hemorrhage. Suprachoroidal hemorrhage after suture-fixating lenses to the sclera and ciliary body area is a potential complication that patients should be advised of preoperatively. PMID- 2199669 TI - Peribulbar anesthesia. PMID- 2199670 TI - Opportunistic smears. PMID- 2199671 TI - A screening programme that worked: discussion paper. PMID- 2199673 TI - Watson-Jones, the book and the Third World. PMID- 2199672 TI - On insight and psychosis: discussion paper. AB - The concept of insight into psychosis has received scant attention in the psychiatric literature. Various types of insight are described after drawing on such sources as phenomenology, clinical observation and experimental psychology. It is proposed that insight is far from an all or none phenomenon but comprises three overlapping dimensions, namely, the recognition that one has a mental illness, compliance with treatment and the ability to re-label unusual mental events (delusions and hallucinations) as pathological. PMID- 2199674 TI - Seaweed and its synthetic analogues in obstetrics and gynaecology 450BC-1990AD. PMID- 2199675 TI - Therapeutics in retrospect: iron carbonate in chorea and tic douloureux. PMID- 2199676 TI - 'Two minutes with venus, two years with mercury'--mercury as an antisyphilitic chemotherapeutic agent. PMID- 2199677 TI - From Da Vinci to Harvey: the development of mechanical analogy in medicine from 1500 to 1650. PMID- 2199678 TI - The death of Mozart. PMID- 2199680 TI - Synergistic activation of transcription by multiple binding sites for NF-kappa B even in absence of co-operative factor binding to DNA. AB - Regulation of eukaryotic genes is largely governed by multiple cis-acting DNA sequences recognized by specific transcription factors. The transcription factor NF-kappa B has been implicated as an important regulator of cellular and viral genes, including those of immunoglobulin kappa light chain, interleukin-2, beta interferon, HIV-1 and cytomegalovirus. We have analyzed the effect of increasing the number of NF-kappa B sites, located directly upstream from the TATA box. Four copies of the sequence gave a more than 100-fold stimulation relative to a single copy, suggesting that NF-kappa B proteins act synergistically to bring about this dramatic increase in transcription. By DNase I footprinting we demonstrated factor binding to two adjacent NF-kappa B sites in vitro. However, we found no evidence for co-operative binding to these DNA sites. We propose that the high transcriptional activity results from another type of co-operation, based on multiple weak interactions of the NF-kappa B factors with another component of the transcription apparatus, perhaps RNA polymerase II itself. PMID- 2199679 TI - Genetic analysis of clathrin function in yeast. AB - The use of yeast mutants to study the function and dynamics of clathrin-coated membranes has offered new insights into clathrin's role in the secretory pathway and has raised additional questions. Most strains of yeast can incur a disruption of clathrin heavy or light chain genes and remain viable. However, in rare cases, alleles of genes other than clathrin affect the viability of clathrin-deficient cells. The relationship of the products of these genes to clathrin awaits clarification. Phenotypic characterization of clathrin-deficient yeast mutants suggests that clathrin is not essential for the generation of secretory pathway transport vesicles at the ER or the Golgi complex but is required for the intracellular retention of a Golgi membrane protein, Kex2p. With this genetic evidence for clathrin's function in vivo, biochemical and genetic experiments can be designed to address the mechanism by which clathrin effects retention of Kex2p. Clathrin-deficient yeast carry out protein secretion, receptor-mediated endocytosis of mating pheromone, and efficient targeting of newly synthesized vacuolar proteins. These observations challenge aspects of clathrin's proposed involvement in protein transport through the secretory pathway and to lysosomes in mammalian cells. However, the differences are beginning to recede in the face of additional experiments; the formation of clathrin coated vesicles is no longer commonly thought to be obligately coupled to transport through the secretory pathway in mammalian cells (Rothman 1986; Brodsky, 1988), and the role of clathrin in retaining a Golgi membrane protein in yeast may have its precedents in receptor-mediated endocytosis by mammalian cells or in secretory granule formation in endocrine cells. A unified theory of clathrin function is emerging (Brodsky, 1988) which suggests that the clathrin coat assemblage (clathrin heavy and light chains and the associated proteins) acts as a facilitator of intracellular protein transport by sorting and concentrating cargo molecules. The results from studies of clathrin-deficient yeast support this theory. Future experiments will determine whether clathrin provides its functions at different transport stages in different organisms or whether all eukaryotic cells employ clathrin at the same stages of intracellular protein transport. PMID- 2199682 TI - Recombinant interleukin-2 and adoptive immunotherapy alternated with dacarbazine therapy in melanoma: a National Biotherapy Study Group trial. AB - We evaluated adoptive cellular therapy with recombinant interleukin-2 (rIL-2) plus lymphokine-activated killer (LAK) cells alternating with sequential dacarbazine chemotherapy in 27 patients with metastatic melanoma. rIL-2 was given to the patients as a 5-day continuous-infusion priming cycle followed by 1 day of rest, 4 days of leukapheresis for in vitro LAK cell expansion, and then 4 1/2 days of continuous rIL-2 infusion in conjunction with reinfusion of LAK cells during the first 3 days of the continuous infusion. Two weeks later, patients received dacarbazine (1,200 mg/m2) chemotherapy. Two patients achieved complete remission, and five achieved a partial remission for a response rate of 26% (95% confidence interval = 12%-47%). Three patients had mixed responses. The partial and mixed responses were brief, ranging from 1 month to 6 months, whereas the two complete responses have been sustained for 13+ and 24+ months. There were no additive toxic effects except for thrombocytopenia, which delayed treatment in two patients. Alternating adoptive immunotherapy and dacarbazine chemotherapy appear to be reasonably tolerated by patients, but the response rate is not clearly better than that achieved with other rIL-2 regimens or with chemotherapy alone. PMID- 2199681 TI - Effects of tamoxifen therapy on lipid and lipoprotein levels in postmenopausal patients with node-negative breast cancer. AB - We conducted a 2-year, randomized, double-blind, placebo-controlled toxicity trial of therapy with tamoxifen (10 mg twice a day) in 140 postmenopausal women with a history of breast cancer and histologically negative axillary lymph nodes. These women had been treated with surgery with or without radiotherapy. At a 3 month evaluation, tamoxifen-treated women showed a significant decrease in fasting plasma levels of total cholesterol and low-density lipoprotein (LDL) cholesterol, which persisted at 6- and 12-month evaluations. During the first 12 months, plasma triglyceride levels increased; small but significant decreases in high-density lipoprotein cholesterol (HDL) were observed in tamoxifen-treated women, but ratios of total cholesterol to HDL cholesterol and of LDL to HDL cholesterol changed favorably. While data relating lipid/lipoprotein profiles and cardiovascular disease are limited in women, current evidence suggests that total cholesterol and possibly low-density lipoprotein cholesterol are risk factors. We conclude that during the first 12 months of treatment, tamoxifen exerts a favorable effect on the lipid profile in postmenopausal women with early stage breast cancer. PMID- 2199683 TI - The hospital trauma team: a model for trauma management. AB - A triage system was established as the initiating mechanism for a trauma team response to assist the assessment and early management of patients presenting to an accident and emergency department. A checklist of triage criteria was used. During a 6-month period, 342 patients (29.7% of trauma admissions) satisfied the triage criteria, which should have resulted in an average of 1.9 trauma team calls per day. Staff compliance with the triage tool was 75.4%. The overtriage rate for the checklist criteria was 52.7%. The triage tool identified patients with severe injuries who were not initially considered sufficiently injured to justify initiation of the trauma team response. The sensitivity of the triage tool in identifying patients with serious injury was 95.0%. Comparison of the review with a similar review performed 12 months earlier demonstrated that staff compliance with initiating the trauma team response had improved. Using data from 564 patients from both series, logistic regression analysis of the power of the triage criteria to predict serious injury contributed to a revision of the triage criteria. This trauma triage tool and trauma team response constitute a valid approach to the early hospital management of trauma patients. This system may be more appropriate or achievable in many hospitals than the construction of dedicated trauma reception units or permanent surgical staffing of general Accident and Emergency departments. PMID- 2199684 TI - Implantable sensor for intraoperative and postoperative monitoring of blood flow: a preliminary report. AB - We have developed an implantable 20 MHz Doppler flow sensor, to monitor blood flow in patients after operation. During surgery the sensor is wrapped around a blood vessel and secured in place with a releasable tie. No tissue puncturing techniques are required. The lead wires, together with a release cable, are exteriorized through the chest wall. Several days after operation, the tie is externally released, and the sensor is pulled out. Twenty-seven sensors were implanted in 24 dogs for up to 16 days. All were extracted successfully with minimal visible behavioral reaction in the awake dogs and caused no thrombosis or vascular damage. The Doppler velocity signals had excellent linear correlations (r = 0.99) with data from electromagnetic flow sensors and timed blood collections. In addition, the sensors were applied to coronary artery bypass grafts in 31 patients for up to 2 days after operation. High-quality signals were obtained, and intraoperatively recorded signals agreed well with simultaneous electromagnetic flow tracings. All sensors were extracted with minimal discomfort to the awake patients and with no complications. Thus, the implantable flow sensor is a safe, reliable, accurate, and simple method for intraoperative and postoperative monitoring of blood flow in vessels 2.5 to 5 mm in diameter. PMID- 2199685 TI - A rapid, accurate, noninvasive technique for diagnosing critical and subcritical stenoses in aortoiliac arteries. AB - Accurate hemodynamic evaluation of the aortoiliac system for the purpose of determining the need for an inflow procedure currently requires invasive pressure measurements. This study was undertaken to evaluate a noninvasive technique with the aortofemoral transfer function. Twenty-eight human aortoiliac segments were studied with intraarterial pressure measurements, with and without papaverine injection, and by calculation of the Doppler-derived mean power frequency index obtained by digital signal processing of aortic and femoral spectra. The procedure is menu driven and can be performed by any duplex ultrasound technologist. This technique involves recording 20 aortic and 20 femoral Doppler signals, requiring less than 1 minute of data acquisition time. Intraarterial pressure measurements were used to classify arteries into the three following groups: (1) normal arteries, (2) arteries with subcritical stenoses, and (3) arteries with critical stenoses. The mean power frequency index of group 1 arteries (n = 7) was 0.63 +/- 0.04, of group 2 arteries (n = 6) was 0.46 +/- 0.02, and of group 3 arteries (n = 15) was 0.21 +/- 0.05. These mean power frequency index values were significantly different by analysis of variance (ANOVA) (p less than 0.0001). Each group could be differentiated from the other groups with a sensitivity of 0.83 to 1.00, a specificity of 1.00, and an accuracy of 0.92 to 1.00 compared to intraarterial pressure measurements, including papaverine testing. Measurement of the mean power frequency index is a rapid, noninvasive technique that diagnoses and quantifies aortoiliac stenoses with an accuracy similar to intraarterial pressure measurements. PMID- 2199686 TI - In situ cannulation, microgrid follow-up and low-density plating provide first passage endothelial cell masscultures for in vitro lining. AB - A rapid and reliable harvest and culture technique was developed to provide a sufficient number of autologous endothelial cells for the confluent in vitro lining of cardiovascular prostheses. Enzymatic endothelial cell detachment was achieved by the in situ application of collagenase to short vessel segments. This harvest technique resulted in a complete lack of contaminating smooth muscle cells in all of 124 cultures from nonhuman primates and 13 cultures from human adults. The use of a microgrid technique enabled the daily in situ quantification of available endothelial cells. To assess ideal plating densities after passage the population doubling time was continuously related to the cell density. Surprisingly, a low plating density of 1.5 X 10(3) endothelial cells/cm2 achieved 43% shorter cell cycles than the usual plating density of 1.0 X 10(4) endothelial cells/cm2. Moreover, low density plating enabled mass cultures after one single cell passage, thereby reducing the cell damaging effect of trypsin. When the growth characteristics of endothelial cells from five anatomically different vessel sites were compared, the external jugular vein--which would be easily accessible and dispensable in each patient--proved to be an excellent source for endothelial cell cultures. By applying in situ administration of collagenase, low density plating and microgrid follow-up to adult human saphenous vein endothelial cells, 14,000,000 first passage endothelial cells--sufficient for the in vitro lining of long vascular prostheses--were obtained 26.2 days after harvest. (95% confidence interval:22.3 to 32.2 days). PMID- 2199687 TI - [Tosufloxacin tosilate]. PMID- 2199688 TI - [Experimental and clinical studies on cefodizime in pediatrics]. AB - Cefodizime (CDZM), a newly developed injectable cephem antibiotic, was given via bolus intravenous injection at each of 3 dose levels of 10, 20 and 40 mg/kg to each 3 children, and serum and urinary levels and urinary recovery rates were followed. A total of 57 patients received CDZM in the following regimen via bolus intravenous injection, and clinical efficacies, and microbial responses were evaluated. Mean dosage per application: 20.9 mg/kg, number of application per day: between 2 and 4 (2 times for 3 patients, 3 for 26 patients and 4 for 28 patients), mean duration of the therapy: 1 week. Patients consisted of 1 case of peritonsillar abscess, 2 acute bronchitis, 38 pneumonia, 8 urinary tract infection, 1 staphylococcal scalded skin syndrome, 2 cellulitis, 4 purulent lymphadenitis and 1 typhoid fever. In addition to the patients mentioned above 6 patients who dropped out were involved in the evaluation of adverse reactions and influence of the drug on laboratory test data, and the following results were obtained. 1. Five minutes after bolus intravenous injection in doses of 10, 20 and 40 mg/kg, serum levels determined by the bioassay method were at their maxima, i.e. 114.0, 264.6 and 461.6 micrograms/ml, respectively. Serum levels of drugs were dose-dependent throughout all the dosage levels tested. Mean serum half-lives of the drug were 1.757, 1.552 and 1.668 hours, respectively, for the 3 dose levels. Serum levels of the drug determined by the HPLC method were similar to those by the bioassay method: The maximum serum levels occurred at 5 minutes after administration, mean maximum concentrations were 105.5, 264.0 and 461.7 micrograms/ml for the 3 dose levels, and a dose response was noted for the 3 dose levels. The half-lives were 1.755, 1.598 and 1.668 hours, respectively. 2. Mean maximum concentrations in urine determined by bioassay for 2 of 3 cases received 10 mg/kg and 3 cases each given 20 and 40 mg/kg of CDZM were 884.3, 3,061 and 7,352 micrograms/ml, respectively, in the first 2 hours after administration. These levels were also dose-dependent. Mean recovery rates were 74.4, 78.4 and 71.5%, respectively, in the first 8 hours after administration. Mean maximum concentrations in urine measured by HPLC were similar to those determined by bioassay, i.e. 962.3, 3,404 and 7,899 micrograms/ml in the first 2 hours. They were, also, dose-dependent. Mean recovery rates were 82.1, 86.0 and 76.5%, respectively, in the first 8 hours after administration. The HPLC determinations gave slightly higher levels than the bioassay.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2199689 TI - [Combined effect of sulbactam/cefoperazone and other antibiotics against clinical isolates of multi-resistant strains. I. Effect of sulbactam against beta-lactams resistant strains and in vitro combined effect of sulbactam/cefoperazone with each of piperacillin, latamoxef, ceftazidime, fosfomycin and doxycycline]. AB - We evaluated relationships between production of beta-lactamase and their resistances to beta-lactams, effect of sulbactam (SBT), a beta-lactamase inhibitor, against beta-lactam resistant strains, and combined effect of sulbactam/cefoperazone (SBT/CPZ) with other antibiotics against multi-resistant strains. Through these studies, we obtained the following results. 1. Most of the strains resistant to beta-lactams were beta-lactamase producers. 2. Relationships between the production of beta-lactamase and their resistances to beta-lactams indicate that their resistances generally were the highest in producers of both penicillinase (PCase) and cephalosporinase (CEPase), moderate in producers of either PCase or CEPase, and the lowest in beta-lactamase non-producers. Most of highly-resistant strains of MRSA appeared to be beta-lactamase non-producers though some exceptions were observed among methicillin-resistant Staphylococcus aureus (MRSA), Serratia marcescens and Pseudomonas aeruginosa. 3. SBT showed good effect against PCase producers, moderate effect against producers of both PCase and CEPase, little effect against CEPase producers, and no effect against beta lactamase non-producers. 4. Results of combined effect of SBT/CPZ with other antibiotics indicated that good synergism was obtained by combining SBT/CPZ with fosfomycin (FOM) or piperacillin against multi-resistant strains of Proteus spp., Enterobacter cloacae, and S. marcescens, by combining SBT/CPZ with ceftazidime (CAZ) or FOM in methicillin-sensitive S. aureus and by combining SBT/CPZ with CAZ in P. aeruginosa. 5. Better synergism was obtained with the higher concentrations of antibiotics. PMID- 2199690 TI - [In vitro susceptibility of Escherichia coli and Klebsiella sp. to antibiotics]. AB - A nationwide susceptibility survey of clinical isolates of Escherichia coli and Klebsiella pneumoniae initiated in 1980 was continued for the 8th consecutive year. A total of 4,421 strains of E. coli and 2,825 strains of K. pneumoniae isolated mainly from urine, sputum and pus, were obtained from 69 hospitals throughout Japan during the 2 years (1986-1987). MICs were determined using the agar plate dilution method (Mueller-Hinton agar, BBL) with inoculation of 10(8)CFU/ml bacteria. Antibiotics tested in this survey were 2 penicillins, 7 cephems and 2 aminoglycosides. Most of the strains of the two species of bacteria were susceptible to ceftizoxime (CZX), cefotetan (CTT), latamoxef (LMOX), cefotiam (CTM) and cefmetazole (CMZ) and also gentamicin (GM) and netilmicin (NTL) were active against both species of bacteria. About 90% of the E. coli strains were inhibited at a concentration of 0.20 micrograms/ml of CZX, 0.39 micrograms/ml of LMOX, 0.78 micrograms/ml of CTT, 1.56 micrograms/ml of CTM or NTL, or 3.13 micrograms/ml of CMZ or GM. Most of the strains were resistant to ampicillin (ABPC) and piperacillin. For the strains of K. pneumoniae, similar results were obtained. Yearly changes in susceptibility of E. coli and K. pneumoniae were not obvious with ABPC, cefazolin, CMZ or GM. No significant differences were observed during 1986-1987 in susceptibilities of the isolates of both species of bacteria due to different clinical specimens. These results suggest that the 2nd and the 3rd generation cephems and aminoglycosides, alone or in combination, may be efficacious in treating infections due to E. coli and K. pneumoniae. PMID- 2199691 TI - [Pharmacokinetics and clinical evaluations on aztreonam in perinatal infections in obstetrics and gynecology. A study of aztreonam in the perinatal co-research group]. AB - Pharmacokinetics and clinical studies on an injectable monobactam antibiotic aztreonam (AZT), were carried out in perinatal infections in obstetrics and gynecology and the obtained results are summarized as follows. 1. Pharmacokinetic study (1) Upon one-shot intravenous injection of AZT 1 g before delivery, maternal serum concentration of AZT was 89.0 micrograms/ml immediately after the injection and a half-life (T 1/2) of 0.96 hour was observed. Umbilical-cord serum concentration showed a peak value of 16.5 micrograms/ml at 1.26 hours after the injection and gradually decreased with a T 1/2 of 1.91 hours. The transfer into amniotic fluid was observed and the peak value of AZT in amniotic fluid reached 12.9 micrograms/ml at 5.57 hours after the injection and slowly decreased thereafter with a T 1/2 of 4.42 hours. Transfer and disappearance in one-shot 2 g intravenous injection and 1 g intravenous drip infusion (1 hour) of AZT were very similar to the results obtained with the one-shot 1 g intravenous injection. (2) The residual serum concentration in neonates after one-shot 1 g intravenous injection of AZT to the mother was almost below the detectable limit. Transfer of AZT into milk was scarcely recognized. 2. Clinical studies (1) AZT was injected to 47 cases with various perinatal infections and it was more than "effective" in 45 cases with an efficacy rate of 95.7%. Also, all the 12 cases to which AZT was administered for prophylaxis of infections showed prophylactic effect. Bacterial eradication was obtained with 25 strains out of 29 aerobic Gram-negative bacteria, but 1 strain "persisted" and for 3 strains results were "unknown", hence an eradication rate of 96.2% was obtained. However, AZT treatment resulted in a little lower eradication rate against Gram-positive bacteria. (2) One case (1.3%) of minor degree of urticaria was found as a side effect, and one case each of eosinophilia and elevation of GOT, GPT and Al-P was observed as abnormal laboratory value. From the above results of pharmacokinetics and clinical evaluation, it has been concluded that AZT is a useful and highly safe drug in various perinatal infections and prophylaxis. PMID- 2199692 TI - [Identification of enterotoxic Escherichia coli by hybridization with nucleic acid probe]. PMID- 2199693 TI - [An undifferentiated carcinoma of the esophagus--a case of an elderly patient]. AB - Reported is the case of an undifferentiated carcinoma of the esophagus that had developed in an 80-year-old man. This polypoid a tumor was an elevated nodular mass, 9 x 5 cm in diameter, that had invaded the muscle layer. Microscopically, the tumor was composed of small polygonal cells with hyperchromatic nuclei that were unaffected by either Grimelius or PAS staining. An epidermal growth factor immunoreactivity was found in a few of the tumor cells. Ultrastructurally, the tumor cells had abundant ribosomes, a rough endoplasmic reticulum, and mitochondria. Coamplification of HST-1 or INT-2 genes was not observed by slot blot analysis. The patient is now well with no evidence of a tumor recurrence or a distant metastasis 11 months after surgery. PMID- 2199694 TI - [A case of long surviving gastric cancer with an malignant acanthosis nigricans]. AB - Reported the case of a 73 year old female who was diagnosed as having a gastric cancer with malignant acanthosis nigricans and had a long survival, totaling about 8 years 6 months after operation. Further, her skin lesion completely disappeared. In general, a gastric cancer with malignant acanthosis nigricans is said to have a very poor prognosis and an analysis of recent cases has indicated that the average survival is about 10 months. The reason for such a bad prognosis is thought to be that the diagnosis of a gastric cancer with malignant acanthosis nigricans is usually determined only after the cancer is far advanced. PMID- 2199695 TI - [An inflammatory pseudotumor of the appendix]. AB - A 41-year-old male, complaining of an abdominal pain and suspected of having acute appendicitis, underwent examination on hospitalization. Ultrasonography revealed a tumorous lesion of the appendix. Thus, a laparotomy was performed and mass lesions were found in the mid and distal parts of the appendix. A subsequent histological examination revealed an inflammatory pseudotumor consisting of remarkable eosinophilic cell and fibroblastic infiltrations, similar to that seen in a inflammatory fibroid polyp (Helwig). Although such lesions, polypoid in appearance, have been found to occur in the stomach and intestines, to find them in the appendix is extremely rare. In this instance, as the growth of this mass of lesions was more predominant in the wall rather than in intraluminal area, it was decided that pseudotumor was the appropriate term to describe this case. PMID- 2199696 TI - Approaches to more effective induction of cytodifferentiation of transformed cells and potential for cancer treatment. AB - Conceptually, the use of cytodifferentiation agents to suppress oncogenicity may prove most effective in long-term continuous treatment of patients whose tumors display some inherent expression of differentiated characteristics. This is the case in many pre-malignant lesions. The difficulty in evaluating the therapeutic role for HMBA is often times in separating in vivo cytotoxic from cytodifferentiation effects. Only with further studies will it be determined whether these and other cytodifferentiation agents are therapeutically useful and whether study of the mechanism faction of these agents provides additional understanding of the processes of cellular transformation and differentiation with which they interact. PMID- 2199697 TI - [Detection of minimal residual leukemic cells in acute leukemia]. PMID- 2199698 TI - [Detection of bacterial virulence factors]. AB - Several newly developed methods, including immunological and DNA hybridization techniques, have been recently introduced in clinical diagnosis. Target molecules for these detection methods are either avirulent materials or virulence factors specific to the individual causative pathogen. Examples requiring the detection of bacterial virulence factors for the accurate identification of causative agents are increasing; for example differentiation of enterotoxigenic Escherichia coli from nonpathogenic E. coli, and identification of cholera toxin-producing (or non-producing) V. cholerae 01. Recent progress in the detection of virulence factors is described. Advantages and disadvantages of various detection methods of bacterial virulence factors are also discussed. PMID- 2199699 TI - [Guidelines of initial diagnostic procedures for bacterial infectious disease]. AB - The practice of the initial diagnostic procedures for infectious disease in febrile patients is important. The rational screening steps to the correct diagnosis of infections are: 1) thorough history taking and physical examination (identification of the organs affected), 2) simpler essential laboratory tests such as white blood cell count, microscopy of blood smear, determination of C reactive protein, electrocardiography and chest x-ray film (confirmation of infection), 3) direct or indirect demonstration of pathogenic organisms by stain enhanced microscopy and culture of specific specimens (identification of etiologic organisms). Extensive culture and serologic testing on febrile patients for identification of organisms depend on individual basis. Indeed, medical care is a team effort with collaboration of doctors, nurses and technologists. More importantly the doctor in charge is fully responsible for interrogation and examination of the patients, interpretation of laboratory results, diagnoses and treatments. PMID- 2199700 TI - [The problems of the report in microbiological examination--ideological and technological aspects]. AB - In the report of microbiological examination, clinicians are required to differentiate infectious diseases from other diseases, to determine the causative organism, and to select suitable antimicrobial agents for chemotherapy. To obtain accurate results, good material must be collected and suitable methods applied. In the microbiological field, rapid diagnosis is very important. New immunological and genetical new methods are being used, to obtain earlier laboratory results and these methods will be commonly used in the not-too-distant future. On the other hand, recently opportunistic infections have increased in hospital. The causative organism and the clinical role of such isolates are very difficult to determine. Such information as the underlying disease, number of leucocytes, and premedication, of the patients must be studied carefully. In future, the laboratory should play the role of the information center for infectious diseases and chemotherapy, but there are very few medical specialists in this field in Japan, which makes it very hard to establish these systems in many hospitals. PMID- 2199701 TI - [Chromosome aberrations and genes in human and experimental leukemias]. AB - Although determination of chromosomal abnormalities may be of limited usefulness for the diagnosis of leukemia, the recent advances in the molecular mechanism associated with chromosome aberration has been rapid. Chromosome translocation in Burkitt lymphoma and chronic myeloid leukemia was the most striking evidence for the oncogene activation. Other specific chromosome abnormalities for FAB classified leukemias are also known. Translocated type of chromosome abnormalities between immunoglobulin or T-cell receptor genes and oncogenes may also affect the T and B-cell leukemogenesis. However, the role of trisomies found in human and experimental leukemias and the gene dosages had been thought to be most important until 1982, has not been unclear. Many types of phenotypically heterogeneous leukemias have been reported. t(4 ; 11) acute leukemia is one such leukemia which shows early B-cell and myelomonocytic nature. Heterogeneous leukemias have been called biphenotypic, hybrid and acute mixed leukemias. The terminology must be used the unified. Recent trials to use paraffin-fixed tissues and bone marrow smear for molecular analysis has been successfully reported. Basic analysis on the DNA degradation mechanism revealed the enzymatic activity might play an important role before the complete fixation. PMID- 2199702 TI - [Lipid metabolism and aging]. AB - Lipids have important biochemical functions, but their excess in plasma is a risk factor for atherosclerotic disease. After puberty, the plasma total and low density lipoprotein (LDL) cholesterol concentrations increase with age as a consequence of an increase in production and a decrease in catabolism mediated by LDL receptors. On the other hand, the plasma high-density lipoprotein (HDL) cholesterol concentrations remain constant. The correlation between serum cholesterol and coronary risk becomes weak with age but also exists in the elderly, while low levels of HDL cholesterol remain to be a risk. The rise in serum triglycerides with age results mainly from the increase in body weight and the decrease in physical activity. Dietary polyunsaturated fatty acids (PUFAs) such as linoleic acid protect against progression of atherosclerosis in part by their hypocholesterolemic effect. The proportion of linoleic acid in serum phospholipids decreases with age. This change also is a separate risk factor for cardiac and cerebral infarction. Among many prostanoids, prostaglandin I2 has antiaggregatory and vasodilatory effects and thromboxane A2 has the opposite effects. Lipid peroxides which are produced inevitably from PUFAs may damage biomembranes and might accelerate cellular aging. The questions of whether dietary manipulation can reduce the age-related changes in lipid metabolism and can improve cellular functions are of major importance. PMID- 2199703 TI - [Care of cardiac insufficiency and laboratory test informations]. AB - Measurement of serum myoglobin, CK-MM isoforms and CK-MB isoenzyme protein are useful for diagnosis and therapy of acute myocardial infarction (AMI). As latex agglutination turbidimetry of serum myoglobin is an easy and rapid assay method, it can be applied for early diagnosis of AMI and its observation of progress after break out of AMI. CK-MM isoforms also can be applicable for early diagnosis of AMI. The assay method of CK-MB isoenzyme protein by immunochemiluminescence is useful for anticipating the infarct size of AMI since this format is not influenced by CK-BB, myokinase, or mitochondria CK. PMID- 2199704 TI - [Pathogenesis and treatment of hypertension]. AB - Many hypotheses have been advocated to explain the pathogenesis of essential hypertension: Guyton's autoregulation theory, the natriuretic hormone theory represented by de Wardner, the sympathetic nervous system theory, and the genetic theory etc. However, none of these theories alone explain the single etiology of hypertension and as stated in Page's Mosaic theory, complicated interaction of many factors has been implicated. We have performed a series of studies to evaluate the interaction between the pressor and depressor systems in relation to salt balances and found in general that hyperfunction of the pressor system and the reduced activity of the depressor systems exist in essential hypertension. Many substances also have been found to be involved in the blood pressure regulation and recently endothelin, a most potent pressor peptide which derives from endothelial cell, was discovered and synthesized by Yanagisawa et al. and its pathophysiological roles are now being extensively investigated. On the other hand, the development of many antihypertensive drugs with different modes of action has enabled us to individualize the treatment of hypertension. Further development of drugs with fewer adverse side effects, whether symptomatic or of abnormality in the clinical laboratory data, and which can maintain or even improve the quality of life is mandatory to pursue life-long treatment of hypertension for successful prevention of the fatal vascular complications. PMID- 2199705 TI - [Structure of hepatitis B virus and its related serological markers]. AB - Hepatitis B virus (HBV) is a small DNA virus belonging to hepadnaviridae. Genomic DNA of HBV has four open reading frames representing the S gene with pre-S1 and pre-S2 regions for envelope protein, the C gene coding for a nucleocapsid protein, the P gene for the putative DNA polymerase, and the X gene encoding a protein with transcriptional transactivating function. The C gene is preceded in phase by the precore region. Recently, this region has been attracting attention because of its role in the synthesis and secretion of HBe Ag. It has been postulated that HBV mutants with precore region defects prevail in persistently infected hosts along with seroconversion to anti-HBe. Recent advances in molecular biology have enabled us to detect minute amounts of HBV DNA by means of polymerase chain reaction (PCR) and to analyze gene function in detail. The advanced techniques and conventional serological assay systems will help in clarifying the pathogenesis of acute and chronic hepatitis B, in preventing and eradicating HBV infection. PMID- 2199706 TI - [Diagnosis of type B hepatitis]. AB - Since 1965, when Blumberg discovered the Australia antigen, the hepatitis B surface antigen (HBsAg), the research on viral hepatitis has rapidly progressed. The identification of specific hepatitis B associated antigens and antibodies in blood, and liver tissue, together with the improvement of detection systems, have enhanced our knowledge about the mechanism of liver injury and the natural history of hepatitis B virus (HBV) infection. Now it has been recognized that HBV has no direct cytopathic effect on hepatocytes and that hepatocyte necrosis is associated with the virus induced immunological reaction of the host. From the reaction, there are two types of HBV infection, i.e., transient (acute) and persistent (chronic) infection. In addition to the conventional measurements, such as HBsAg, anti-HBs, anti-HBc, HBeAg, anti-HBe and anti-IgM HBc, recently pre S1, pre S2 antigen/antibody systems and polymerized human albumin receptor and antibody have been developed. The significance of the detection of these antigen/antibody systems was discussed. On the other hand, to determine the presence of HBV, the state of HBV replication or the infectivity directly, HBV associated DNA polymerase and HBVDNA should have been detected. (Very recently, the polymerase chain reaction method has been introduced to detect very small amounts of HBVDNA). In this presentation, the change of these viral markers in various cases was shown, and especially emphasized was anti-IgM HBc in acute hepatitis and HBeAg/Ab status in chronic liver disease. Lastly, the present state of Interferon therapy for type B chronic hepatitis was mentioned. PMID- 2199708 TI - [Medical decision making: its history and technical terms]. AB - Medical decision making, an application of decision sciences to medicine, has been increasingly recognized as an important clinical armamentarium in the past several decades. Clinical medicine abounds in uncertainties arising from the very nature of clinical data and physicians' judgments. These uncertainties provide room for decision sciences to be widely used in clinical medicine. There are two major research areas in medical decision making, i.e., prescriptive and descriptive approaches. The prescriptive approach, an endeavor to explore how decisions should be made, is quantitative and probabilistic, and employs decision analytical procedures which are designed to maximize expected value or utility. An example of a decision tree is shown as well as such essential technical terms as decision node, chance node, averaging out, folding back, sensitivity, specificity, predictive values, Bayes' theorem, and expected value of clinical information. The descriptive approach, on the other hand, is related to how people behave. In this context, strict meaning of judgment and decision making, some heuristics and psychological pitfalls, and the necessity of elucidating patients' preferences, though difficult, are recapitulated. PMID- 2199707 TI - [Prevention of hepatitis B virus infection]. AB - The incidence of the carrier of hepatitis B virus (HBV) in Japan is about ten times higher than that in U.S.A. and Western Europe. Countermeasures against HBV infection have been proposed on a national basis. The main route of HBV infection is due to contamination of blood and secretion from the carrier of HBV. The contamination would occur in many circumstances such as in the case of blood transfusion, needle accidents in hospital, vertical infection from mother to baby at the time of delivery and infection within family members. To prevent the posttransfusion hepatitis due to HBV, rapid and high sensitive measurement of HBs antigen should be introduced. Countermeasures have begun against the vertical infection from mother to baby at the time of delivery by the National Treasury. Already, a good result has been obtained. Recently the vaccination against HBV is generally performed. However, a low incidence of people have a high anti-HBs titer for a long period. The new countermeasure against this problem should be worked up as soon as possible. PMID- 2199710 TI - [Recent progress in computer-assisted laboratory diagnosis]. AB - To assist the physician in the clinical decision making process, the CALD (computer-assisted laboratory diagnosis) system was constructed. This was serially connected with a multi-center laboratory information system for practical use. From among the examples of CALD used, a diagnostic system for the blood spectrum and peripheral hemogram was selected for the evaluation of the principle and usefulness, and for a discussion of further problems. The method of selection of suitable tests for hepatobiliary disease screening (from a normal group and 10 groups of other diseases) and its diagnostic logic and usefulness of quantitative diagnosis using a discriminant curve were then discussed. The optimal combinations were most often found to involve 1-5 tests. Near maximal diagnostic efficiency was achieved by 50-100 combinations. The diagnostic efficiency of the optimal test was higher than expected, with a range of 80-100% (92.7% on average). PMID- 2199709 TI - [A decision analysis model in laboratory medicine--appropriate usage of microbiological examination in women with dysuria]. AB - Decision analysis is a noteworthy methods to solve complex medical problems and select best alternative under uncertainty, and its practical applications in laboratory medicine are anticipated for appropriate usage of laboratory resources. From the view of classical microbiology, it is necessary to identify bacteria causing an infection and select sensitive antibiotics to this pathogen. Decision analysis was used to estimate the clinical and economic implications of microbiological testing for urinary tract infections at the initial visit for all women with acute dysuria. A strategy of initial culture was compared with a strategy involving the use of culture only for patients with symptoms persisting 3 days after initial therapy (wait 3 days strategy). Expected direct cost and medical care days were 10,748 yen and 7.12 days for initial culture strategy and 6872 yen and 7.24 days for wait 3 days strategy. Sensitivity analysis showed that initial culture strategy was not cost effective when the frequency of antibiotics resistant organisms would be increased or required days to obtain microbiological tests results would be decreased. PMID- 2199711 TI - [The application of medical decision making to the mass screening: the basic principles on ROC analysis]. AB - The basic principles on receiver-operating characteristic (ROC) analysis were discussed. ROC curves showed the discriminative ability of a test by the position of the full curve in a graph plotting the relation between the true positive rate (TPR) and the false positive rate (FPR) over a wide range of cut-off points of a test. The increase in the area under the ROC curve, or the shift of the curve upward and to the left in the diagram means that the test has better discriminative ability. A manual was given to conduct the ROC analysis with special reference to calculation of TPR, FPR, and the area under the ROC curve. Also discussed was the method to decide the best or optimal cut-off point as the positivity criterion of a test, based on the ROC analysis. Attention was paid to balance the risk of false negatives and false positives. We made an equation to decide the best cut-off point, which showed us the variables to be considered in the analysis of cut-off problems: the prevalence of disease and the outcome associated with each state classified by the test, i.e., true positive, false positive, true negative, and false negative. PMID- 2199712 TI - [Comment on the application of medical decision making]. AB - There are three features in decision making in medicine. Decisions must be made on uncertain diagnostic and therapeutic information, a selected course of action may have an unwanted outcome, and finally, actions can not be retried from the beginning. We often assume that, by ordering a test, we can obtain more information to assist better decision making. It should be pointed out, however, that the test itself may be harmful and/or costly, may cause delay of treatment, and may misguide the decision by giving a false result. The benefit/risk ratio of choosing a test depends on the prior probability of disease, sensitivity and specificity of the test, and the outcome (utilities) of the correct and incorrect diagnosis. By drawing decision trees and making a sensitivity analysis, decision analysis helps to make the balance explicit. PMID- 2199713 TI - [Study of non specific reactive phenomena in EIA method of CA 125]. AB - We studied the false positive phenomena in immunoassay of CA 125 using mouse monoclonal antibody, and studied the natures of interfering substances. The serum CA 125 level in 405 patients was determined simultaneously by using the EIA and RIA methods. The overall correlation was good between CA 125 levels of the EIA and RIA methods. However, CA 125 levels in 41 cases were remarkably higher in the EIA method as compared with the RIA method. None of these patients had any disease that was known to result in elevation of the serum CA 125 level. The CA 125 activity of sera from five patients with remarkably discrepant values was contained in the column fractions corresponding to a molecular weight of human IgM in gel chromatography of TSK gel G 4000 SWXL that was smaller than the molecular weight of CA 125. To further determine whether IgM was involved in the CA 125 activity, we investigated the effect of adding anti-human IgM serum to discrepant sera. CA 125 activity was markedly reduced by the antiserum, whereas CA 125 activity in non-discrepant sera were not effected by this antiserum. Thus, data obtained from this group of experiments indicate that the interfering material in discrepant serum is IgM. PMID- 2199714 TI - [Magnetic resonance tomography in the examination of the heart]. PMID- 2199715 TI - [Time of surgery on patients with chronic aortic valve insufficiency]. PMID- 2199716 TI - [Pulmonary hypertension in ventricular septal defect]. PMID- 2199717 TI - [The effect of various types of stress-limiting therapy on the outcome of myocardial infarction]. AB - A method for computed determination of death probability was used to examine the effects of various modalities of stress-limiting therapy on mortality rates within a month after myocardial infarction. The examination was made in 591 patients with large myocardial infarction. A significant decrease in mortality rates was seen in patients on finoptin and phosphocreatine (by 9.6 and 11.2, respectively) as compared to the expected drop. Other agents given within the first hours of myocardial infarction such as beta-blockers, opioid peptides, sodium oxybutyrate, piracetam, antioxidants were demonstrated to cause no reduction in mortality rates. PMID- 2199718 TI - [Pharmacodynamics, pharmacokinetics and clinical effectiveness of captopril in patients with hypertension]. AB - Captopril was tested for pharmacokinetics. Its hypotensive effect was compared with plasma renin activity (PRA) and blood captopril levels in single and prolonged administrations of its various doses in 58 hypertensive patients. When a single dose (25 mg) of captopril was given, a relationship was found between its hypotensive effect and higher blood concentration, baseline PRA. The detection rate of its antihypertensive effect was not related to the baseline PRA. The efficient and safe dose of captopril was shown to be 75-150 mg daily, maintaining its blood concentration within ranges of 75-175 ng/ml. PMID- 2199720 TI - [Clinical aspects of the progression of nonspecific brachiocephalic aortoarteritis]. AB - Based on the features of the clinical course of nonspecific aorto-arteritis, three types of the course were identified: slowly progressive, rapidly progressive, and recurrent. The progression of the disease and involvement of new arterial beds into the pathological process were found to primarily depend on persistent inflammation. It is suggested that the types of the clinical disease course are directly related to immunological responsiveness. PMID- 2199721 TI - [Comparative evaluation of the effects of isoptin and obsidan on central and cerebral hemodynamics in patients with hypertension during physical exercise]. AB - Isoptin and obsidan were demonstrated to cause a significant increase in exercise tolerance in patients with Stages I and II hypertensive disease. The response of blood pressure to isoptin and obsidan was virtually identical, yet isoptin acted longer. When obsidan was administered, there was a decrease in specific peripheral vascular resistance with a stepwise elevation of blood pressure, whereas isoptin promoted its slight rise with maximally elevated blood pressure. Isoptin administration prevented brain hyperperfusion at maximum blood pressures. PMID- 2199719 TI - [Use of beta 1-adrenostimulants in circulatory failure in patients with chronic inflammatory lung diseases]. AB - In 34 patients with chronic cor pulmonale, the drugs from a group of beta adrenostimulants, nonachlazinum and oxyphedrinum, were tested for effects on their hemodynamics, pulmonary ventilation function, blood gas composition and acid-base balance. In patients with circulatory failure due to lung diseases, nonachlazinum and oxyphedrinum were found to exert a pronounced positive intropic action, to contribute to an increase in cardiac output. The agents may be included into the multimodality therapy of patients with decompensated chronic cor pulmonale. PMID- 2199722 TI - [Blood pressure and relative body weight, alcohol consumption and electrolyte excretion in the FRG and the GDR: the Intersalt Study. The Intersalt Study Group form the FRG and the GDR]. AB - The relationships between body mass index (BMI) and age, alcohol consumption, 24 hr urinary electrolyte excretion, and BP were studied in 588 subjects from three German centers participating in Intersalt, a highly standardized, previously reported protocol. Men and women aged 20-59 were sampled in Bernried, FRG; Cottbus, GDR; and Heidelberg, FRG. The subjects from the three centers did not differ in BMI, level of education, physical activity, cigarette- or alcohol consumption patterns, or urinary Cl excretion. Mean Na excretion was 167, 147, and 172 mmol/24 hr in Bernried, Cottbus, and Heidelberg, while mean K excretion was 72, 55, and 73 mmol/24 hr, respectively. The excretion of these electrolytes was significantly lower in Cottbus than in Bernried or Heidelberg. BMI increased progressively in men with age; in women BMI plateaued until the 5th decade, after which it increased to equal that of men. In individual centers, the excretion of electrolytes was correlated with BMI. Sodium and chloride excretion were highly correlated. The data from each individual center were fitted to a multiple regression model. Age, BMI, sex, and alcohol consumption entered the model. PMID- 2199723 TI - Cardiovascular reflexes during vibration stress. AB - Vibration disease due to hand-held vibratory tools has various symptoms and signs which can be characterized by the severity. They include disorders of the central and autonomic nervous systems, as well as peripheral system disorders. The mechanism of Raynaud's phenomenon in vibration disease is proposed to be: Vibration and cold affect the local vessels and nerves directly, leading to enhanced release of chemical vasoconstrictors. Vibration, noise, cold, ergonomic and biodynamic conditions, and emotional stress during work result in disorders of the central and autonomic nervous systems. In the early stages, the autonomic nervous system may be stimulated, and in the later stages it is suppressed. When local vessel injuries and disorders of the central and local autonomic nervous mechanisms controlling the vessels occur, vasospasms in the fingers develop when the whole body is exposed to cold. The cardiovascular system, other than the peripheral circulatory system, may adapt to vibration stress. The adaptation subsides 7 to 8 years after discontinuation of the use of hand-held vibratory tools. PMID- 2199724 TI - Horror Autotoxicus and homing: implications for autoimmunity. PMID- 2199726 TI - Identification and localization of epidermal growth factor and its receptor in the human glomerulus. AB - Radioimmunoassay for epidermal growth factor (EGF) was performed using the homogenates of glomeruli and tubular preparations obtained from normal human kidneys. EGF-immunoreactive material was 3- to 5-fold higher in the glomerular fractions than in the tubular fraction. By indirect immunofluorescence with a monoclonal antibody, EGF was positive in three of five normal human kidney tissues and in tissues of 24 of 33 patients with proliferative and nonproliferative types of glomerular diseases. Acid-urea treatment of tissue sections to unmask a hidden epitope of the EGF molecule disclosed EGF immunoreactivity in four more kidney specimens. EGF was localized along the glomerular capillary walls and was also present in the arterioles and small arteries. Staining with three monoclonal antibodies recognizing two different epitopes of EGF receptor (EGF-R) was positive in tissues of 2 normal subjects and 15 patients with glomerular diseases. EGF-R was found along the glomerular capillary walls, in peritubular capillaries, and within the epithelial cells of distal tubules and collecting ducts. Immunoelectron microscopy with colloidal gold staining showed that EGF and EGF-R were localized in the plasma membrane of glomerular endothelial cells. Immunofluorescence with or without acid-urea denaturation showed coexpression of EGF and EGF-R in glomeruli of 1 normal subject and 12 patients. This study demonstrated the presence of EGF and EGF-R in human glomeruli. There was no obvious difference in EGF and EGF-R expression in glomeruli derived from normal or diseased state. PMID- 2199725 TI - Another mechanism for the defect in type III collagen accumulation in Ehlers Danlos syndrome type IV: increased intracellular degradation of the procollagen. AB - The nature of type III collagen was examined in the skin and cultured skin fibroblasts from a patient with Ehlers-Danlos syndrome type IV. Although the culture medium contained a much lower amount of Type III collagen than the controls, the cells contained an apparently normal amount of Type III collagen. The patient's Type III procollagen showed no abnormalities in apparent molecular weight, the peptide length as examined by cyanogen bromide cleavage, the genomic DNA size including its C- and N-propeptide portion, mRNA size, or thermal stability; but a pulse-chase study revealed prolonged retention of the type III collagen in the cells. Degradation of Type III procollagen was induced by cell extracts but did not occur in the extracellular space and was inhibited in intact cells by the addition of ammonium chloride or leupeptin to the culture medium. Fluorescent staining showed a characteristic granular deposition of Type III procollagen in the peripheral region of the cytoplasm but no granular deposition of Type I procollagen. These results offer new insight into the mechanism of the decreased amount of Type III collagen in the tissue of patients with Ehlers Danlos syndrome type IV. PMID- 2199727 TI - Glomerular lesions in nonobese diabetic mouse: before and after the onset of hyperglycemia. AB - The natural history of renal lesions in nonobese diabetic mice was assessed. This strain develops a spontaneous overt insulin-dependent diabetes that has a female predominance and an autoimmune pathogenesis. We compared mice that had a normal glucose tolerance test with mice that had a diabetes of 2 to 15 weeks' duration. The glomerular surface area was increased in all diabetic mice regardless of the duration of hyperglycemia. There was an increase in the albumin/creatinine ratio in the urine of diabetic mice. Finally, nonobese diabetic mice all showed mesangial sclerosis that was more pronounced in the diabetic mice. This suggests that this strain is susceptible to glomerulosclerosis and that the occurrence of hyperglycemia results in an increase of glomerular size, mesangial sclerosis, and proteinuria, soon after glycosuria is first demonstrated. PMID- 2199728 TI - What is stuttering? AB - The most definitive evidence about any aspect of stuttering is that listeners are unable to judge unit-by-unit occurrences of it acceptably. This result has been replicated repeatedly in every decade for a half century. Nonetheless, for virtually all research and most clinical practice, stuttering has been defined perceptually as if listeners could identify it accurately. Reasons for this state of affairs and its implications for therapy, theory, and research are analyzed. An alternative speech production definition with its implications is proposed. Further, a diagnostic method of validating authentic stuttering is described, as is an objective for fluency-skill therapy that reduces rather than reinforces avoidance behavior. PMID- 2199730 TI - The relationship between psychopathology and speech and language disorders in neurologic patients. AB - Depression, anxiety, and conversion reaction are common in neurologic patients. These disorders can produce neurologic-like symptoms that either mask or intensify those produced by the neurologic disease. This paper reviews clinical and research findings relating psychopathology to the formation and remediation of speech and language disorders in neurologic patients. The need to consider the psychosocial and psychopathological aspects of neurologic communicative disorders, and the link between emotional and communicative processes, are emphasized. Diagnostic criteria for the identification of psychogenic communicative disorders are outlined. PMID- 2199729 TI - The identification of language impairment in the selection of specifically language-impaired subjects. AB - This review focused on the methods used to identify language impairment in specifically language-impaired subjects participating in 72 research studies that were described in four journals from 1983 to 1988. The single most frequent source of information used in the identification process was found to be test data. There was, however, considerable variability and, often, a lack of clarity regarding the specific number and identity of tests used. More specific findings on test use indicated that researchers routinely assessed both expressive and receptive language and that they used incomplete tests. When test scores used in identification and selection were examined, there was a wide range of score types, and age-equivalent scores were by far the most common and often the only type of score utilized. Conclusions are drawn regarding the impact of these findings on the interpretation and generalizability of this research literature. PMID- 2199731 TI - Description of laryngeal pathologies in children evaluated by otolaryngologists. AB - The purpose of this investigation was to describe the occurrence of laryngeal pathologies and their distribution across age, sex, and race in a pediatric sample. Data were collected on 731 patients seeking evaluation or treatment at a children's hospital otolaryngology clinic. The most frequent laryngeal pathologies were subglottic stenosis, vocal nodules, laryngomalacia, and vocal fold paralysis. For the total sample, laryngeal pathologies were significantly more common to males than females. Laryngeal pathologies were most common in the youngest patients. The distribution of pathologies within each race was similar to that found throughout the total sample. Comparisons with similar investigations are made. Implications for management are discussed. PMID- 2199732 TI - Biliary response to glucagon and insulin following hepatic transplantation in humans. AB - Glucagon and insulin are postulated to be physiologic regulators of hepatic biliary secretion. Effects of these hormones were studied following orthotopic transplantation. Five adult hepatic graft recipients had triple lumen t-tubes placed at the time of surgery and were studied 3 months after surgery. Experiments were performed after cholangiographic confirmation of t-tube placement and function. After overnight fast, t-tubes were inflated and bile was collected. A small quantity was saved for analysis and the remainder was reinfused to maintain enterohepatic circulation. After 1 hr of observation, the patients received a 2-hr infusion of insulin (0.125 U kg-1 hr-1), glucagon (2 micrograms kg-1 hr-1), or 0.9% saline. During saline infusions, all parameters remained stable. As has been previously demonstrated in the canine model and intact patients, bile salt outputs were constant under all experimental conditions. Glucagon stimulated bile secretion by 30% (6.7 +/- 1.5 to 8.7 +/- 1.2 ml/15 min) and inhibited biliary cholesterol output by 47% (16.4 +/- 3.2 to 8.7 +/- 1.5 mg/15 min). Bile flow and lipid secretion were not affected by insulin. Glucagon had profound effects on bile flow and lipid secretion, suggesting effects independent of innervation, while insulin at this dose had no statistically significant effects. PMID- 2199734 TI - Influences of ischemia and reperfusion on the feline small-intestinal mucosa. AB - The alterations of several small-intestinal mucosal enzymes have been examined in cats that underwent different periods (1-4 hr) of occlusion of the superior mesenteric artery, followed by 4 hr of reperfusion. The damage progressed during ischemia and reperfusion from the villus tips to the crypts: first, there was a rapid decrease in the activity of maltase, a brush-border enzyme; a slower decline occurred in two cytoplasmic enzymes, aldolase A (with preferential location in feline villus cells) and lactate dehydrogenase (with an ubiquitous distribution); a lag preceded the decrease in aldolase B (a cytoplasmic enzyme shown to occur mainly in feline crypt cells). For all these enzymes, the initial period of reperfusion was associated with a greater decrease in enzyme activity than persisting ischemia. By determination of the unsedimentable proportion of glutamate dehydrogenase (a mitochondrial matrix enzyme) and of acid phosphatase (a lysosomal enzyme) it was demonstrated that ischemia caused important mitochondrial damage before the cells were lost, whereas no lysosomal damage was observed in any condition. These sensitive parameters of cell damage can serve as a criterion for an adequate evaluation of potential cytoprotective agents. PMID- 2199735 TI - Laboratory models of sepsis and septic shock. AB - That there are so many models of sepsis and septic shock is tacit evidence that none of them are perfect. Although sepsis presents in many forms clinically, most clinicians would probably agree that virtually all severely septic patients manifest respiratory failure and ventilator dependence. Furthermore, failure of organs other than the lungs typically occurs days to weeks after the onset of the septic process. Although early deaths occur commonly in some situations (e.g., meningococcemia, pneumococcal bacteremia in asplenic individuals, Gram-negative bacteremia in the setting of profound granulocytopenia), most deaths due to sepsis occur after a protracted course in an intensive care unit. Thus, for certain important experiments, there is a need for an animal model of severe chronic sepsis characterized by these features: persistent hypermetabolism, low systemic vascular resistance, respiratory failure severe enough to require mechanical ventilation, late (nonpulmonary) organ system failure, and death. Obviously, creation of such a model will require a major commitment of resources, because it will require, in essence, the creation of an animal intensive care unit. Nevertheless, we believe that progress in sepsis-related research would be substantially facilitated were such a model available. Even without such a model, progress will continue in this field. A wide variety of good animal models are already available to investigators. In the next decade, as new methods, such as the powerful tools of molecular biology, are applied to problems related to the sepsis syndrome, these models will be invaluable in improving our understanding of pathophysiology and in developing new and more effective approaches toward therapy. PMID- 2199733 TI - Induction of endogenous tissue antioxidant enzyme activity attenuates myocardial reperfusion injury. AB - Efforts to reduce reperfusion injury have focused on exogenous therapies; however, endogenous attenuation of reperfusion injury can be induced by a single sublethal dose of endotoxin (ETX) prior to ischemia. The purposes of this study were to investigate (i) the early neutrophil-endothelial (PMN-EC) adherence, (ii) the associated myocardial oxidant stress, (iii) the relationship of oxidant stress to antioxidant enzyme activity, and (iv) the correlation of increased antioxidant enzyme activity to myocardial recovery following ischemia/reperfusion (I-R) injury at 36 hr. Rats were administered a sublethal dose (2% of LD50) of endotoxin (500 micrograms/kg, ip, Salmonella typhimurium). At 6 hr, myocardial neutrophil accumulation (histology), hydrogen peroxide (H2O2) levels, and myocardial tissue glutathione (glutathione and oxidized glutathione) levels were determined. At 24 hr myocardial tissue glutathione levels and catalase (CAT) activity were assayed. At 36 hr, myocardial tissue superoxide dismutase, glutathione peroxidase, glutathione reductase, catalase, and glucose-6-phosphate dehydrogenase (G-6-PD) were assayed. At 36 hr, hearts were subjected to a standard (20 min, global, 37 degrees C) ischemic insult followed by reperfusion. At 40 min of reperfusion, ventricular function was assessed (ventricular balloon; ventricular developed pressure +dP/dt, and -dP/dt).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2199736 TI - The hypothesized hormonal control of human sex ratio at birth--an update. AB - I have reviewed the literature on the human sex ratio at birth (W.H. James, 1987 a. Hum. Biol. 59, 721), and proposed a hypothesis to account for its variation (W.H. James, 1987 b. Hum. Biol. 59, 873). Since submitting those papers, some sets of data have been published which bear on the hypothesis and on how it may be tested. In this note some comments are made on these new data sets. The hypothesis proposes that hormone levels of both parents at the time of conception affect the sex of the resulting zygotes. This suggestion is unlikely to gain wide credence unless and until it has been demonstrated that sex ratios can thus be manipulated in experimental animals. This paper is offered in the hope that it may prompt workers to try testing the hypothesis in whatever way is open to them. PMID- 2199737 TI - [The lithotriptor and its widespread use. An example of lack of evaluation of medical technologies]. PMID- 2199739 TI - Localization of the carotid artery within the tonsillar fossa by Doppler flow mapping. AB - Injury to the internal carotid artery during procedures performed in the tonsillar fossa can be catastrophic. Tonsillectomy or uvulopalatopharyngoplasty was performed on 32 patients at the Hospital of the University of Pennsylvania or the Children's Hospital of Philadelphia. Using Doppler ultrasonography, the course of the internal carotid artery in the postsurgical tonsillar fossa was mapped. The results indicate that, in the majority of patients, the internal carotid artery is located between 20% and 60% of the total width across the tonsillar fossa, as measured from the posterior pillar. Appreciation of the surgical anatomy of the tonsillar fossa with respect to the internal carotid artery should contribute to improved intraoperative judgment and further limit the risk of vascular injury during oropharyngeal procedures. PMID- 2199738 TI - [The rational use of medications]. PMID- 2199740 TI - The predictive value of tumor classification compared with results of the British Institute of Radiology fractionation trial in the treatment of laryngopharyngeal carcinoma. AB - Data from a clinical trial involving 734 patients have shown the value and the deficiencies of the current Union Internationale Contre le Cancer's tumor, node, and metastasis classification system for prognostic purposes. The tumor-category classification provides a good discriminant for both nodal involvement and survival; however, the previous node classification system only discriminated between node-negative and node-positive patients, as nodal fixity was not found to be a discriminator. The current anatomical site classification is ambiguous for some laryngeal and pharyngeal subsites, and modifications to the present system based on prognostic values are proposed. A difference in patient age between tumor categories has been shown, and various differences in incidence and survival data for the sexes have been demonstrated. Differences in observed and expected survival rates are related to continued late deaths from tumor. Multivariate analyses have shown that stage grouping is the most powerful prognostic discriminator, followed by anatomical site and age. PMID- 2199741 TI - Tumour cell purging for autologous bone marrow transplantation. AB - Interest in autologous bone marrow transplantation as treatment for haematological disease has increased considerably in the past 10 years. Remission bone marrow can be collected, stored until the patient has received myeloablative therapy, then re-infused. A disadvantage of this form of treatment is the possibility of re-infusion of residual malignant cells. The methods currently available for removal of neoplastic cells from autologous marrow prior to transplantation are reviewed. PMID- 2199743 TI - [Secretory otitis media: current aspects and therapeutic role of adenoidectomy]. AB - The prognostic influence of adenoidectomy on the clinical course of secretory otitis media (S.O.M.) was evaluated in 46 children with abnormal tympanometry, i.e. a flat curve (type B tympanogram) or a middle ear pressure less than 100 mm H2O (type C tympanogram). The children were divided by randomized, blind allocation into one group of 22 subjected to myringotomy with adenoidectomy and another group of 24 subjected to myringotomy without adenoidectomy. All 46 children were followed up by impedance audiometry, pure tone audiometry and otomicroscopy 1, 3, 6 and 15 months after surgery. No significant differences were found between the two groups. Possible pathogenetic mechanisms leading to the development of S.O.M. in the presence of large adenoids are discussed. PMID- 2199742 TI - [The monocyte-macrophage system and acquired immunodeficiency syndrome (AIDS)]. AB - The pathogenesis of HIV infection and the definition of the cell types target of HIV is the crucial background for the improvement of the therapeutic strategies against HIV infection. Monocyte-macrophages (M/M) are easily infected by HIV, and play a crucial role in the maintenance and the progression of HIV-related disease; HIV infection of M/M is the principal cause of HIV-related "dementia complex". Thus it is crucial that drugs used in the therapy of HIV infection are active against HIV replicating in cells of M/M lineage. In this paper the interaction between HIV and M/M is analyzed and the characteristics of viral replication in these cells, and the in vitro antiviral activity of several drugs in M/M are discussed. These data suggest that patients should be treated with drugs, that inhibit HIV also in M/M and, consequently, are able to block the clinical manifestations related to M/M infection, such as "dementia complex". PMID- 2199744 TI - [Pathogenetic and clinical significance of the adhesion molecule expression on T cells of the lung in sarcoid alveolitis]. AB - A double immunofluorescence analysis of CD4+ cell population from bronchoalveolar lavage (BAL) fluid samples of patients with active pulmonary sarcoidosis was carried out. The results showed that, unlike BAL and peripheral blood CD4+ cells of healthy subjects, almost all BAL CD4+ cells of the patients highly express, besides CDw29 antigen, LFA-1 and ICAM-1 adhesion molecules. The co-expression of these molecules on BAL CD4+ cells during high intensity sarcoid alveolitis could represent a marker of immunological memory. The relevant pathogenetic and clinical implications of this observation are discussed. PMID- 2199745 TI - [Computers in emergency medicine]. AB - Computer's applications in emergency medicine are reviewed. In the Emergency Health Care computer science provides support to the solution of medical problems (with diagnostic and medical decision making softwares) and to the management of emergency departments. Computer interfaced to instrumental equipments allows the monitoring of biomedical signals and their transmission at distance. Finally, the possibilities of computer-aided instruction are presented. Teaching methods such as the tutor-system and the simulation are discussed. PMID- 2199746 TI - [Cancer: the history of its study, its epidemiology and the problems]. PMID- 2199747 TI - [The operating room nurse (on the centenary of the A. G. SavinykhHospital Surgical Clinic of the Tomsk Medical Institute)]. PMID- 2199748 TI - Effects of exercise training on the menstrual cycle: existence and mechanisms. AB - This review evaluates the status of the evidence that exercise training affects the menstrual cycle beginning with evidence for the existence of delayed menarche, amenorrhea, and luteal suppression in athletes. A later age of menarche and a higher prevalence of amenorrhea and luteal suppression have been observed in athletes, but there is no experimental evidence that athletic training delays menarche, and alternative sociological and statistical explanations for delayed menarche have been offered. Cross-sectional studies of amenorrheic athletes have revealed abnormal reproductive hormone patterns, suggesting that the GnRH pulse generator in the hypothalamus is failing to initiate normal hypothalamic pituitary-ovarian function. Longitudinal data show that the abrupt initiation of a high volume of aerobic training can disrupt the menstrual cycle in at least some women, but these women may be more susceptible to reproductive disruption than others, and some aspect of athletic training other than exercise (such as caloric deficiency) may be responsible for the observed disruption. Luteal suppression may be an intermediate condition between menstrual regularity and amenorrhea in athletes, or it may be the endpoint of a successful acclimation to exercise training. A potential endocrine mechanism of menstrual disruption in athletes involving the hypothalamic-pituitary-adrenal axis is discussed. Finally, promising future directions for research on this topic are described. PMID- 2199749 TI - Effect of exercise on bone: permissive influence of estrogen and calcium. AB - Estrogen deficiency in postmenopausal women is associated with low lumbar bone mineral density and an increased incidence of fractures of the vertebrae and proximal femur. Estrogen deficiency in premenopausal women with secondary amenorrhea related to athletic training or anorexia nervosa is also associated with decreased lumbar bone mineral density. The purpose of this review is to present four concepts related to the adaptations of bone to physical exercise, as a basis to explain the loss of bone mass in women with athletic amenorrhea. These concepts are based on Lanyon's theory of a Minimum Effective Strain-Related Stimulus. The bone remodeling response to estrogen deficiency is an increase in the rate of bone remodeling activity and in the rate of bone resorption relative to formation, resulting in a net loss of bone mass. In the presence of estrogen deficiency, the stimulus of physical activity is thought first to decrease the rate of turnover and secondly to increase bone formation. Endurance exercise training appears to be an insufficient stimulus to accomplish both tasks, which may explain why these athletes often have low lumbar bone mineral density. PMID- 2199751 TI - Body fat distribution in females: metabolic consequences and implications for weight loss. AB - The main function of adipose tissue is to store triglyceride during relative affluence and to break down this fat and release fatty acids and glycerol when needed. Both the deposition and degradation of lipid are under precise hormonal and neural control. Recently, it has become evident that adipose tissue is not homogeneous and that the regional distribution of fat may be important with respect to metabolism and hormonal responsiveness and, thus, of interest from a number of viewpoints. This review will focus on the physiological significance of differences in adipose tissue distribution and implications for the female. Included will be the hormonal and metabolic consequences of child bearing and the metabolic outcome for chronic disease risk. Furthermore, the influence of the distribution of adiposity on weight loss by diet and exercise, as well as changes in fat and lean tissue, will be examined. Possible directions for future research in this area will be discussed. PMID- 2199750 TI - Metabolic actions of estradiol: significance for acute and chronic exercise responses. AB - Although estradiol (E2) is considered primarily for its role in reproduction, it can exert numerous physiological actions on a variety of tissues. However, there are several difficulties in isolating these actions and determining its impact for in vivo situations. Despite the limitations, it does appear that E2 can alter, under certain conditions, resting and acute exercise metabolism and blood glucose regulation. Specifically, E2 can increase lipid availability and utilization and decrease gluconeogenesis and glycogenolysis. Development of glucose intolerance as a result of insulin insensitivity has also been documented. The mechanisms of E2 may be through direct alterations in key enzyme activity and membrane permeability or indirectly via changes in insulin:glucagon, cortisol, hGH, and catecholamine levels or sensitivity. Future research should focus on understanding the effects of exercise and diet on chronic E2 status and the resulting impact for a variety of conditions that include reproductive and skeletal integrity and predisposing metabolic risk factors for CAD and diabetes. In order to make meaningful correlations between E2 levels and physiological measurements such as bone mineral content, lipid profiles, glucose intolerance, etc., there needs to be a standard guideline for determining and defining one's "estrogen status." Finally, in order to identify underlying mechanisms, an understanding of and appreciation for the interrelationships among the numerous compositional, metabolic, and (neuro)endocrine factors involved is needed. A general model is presented, along with specific applications, to study these interactions. PMID- 2199752 TI - Fiber-type discrimination in disuse and glucocorticoid-induced atrophy. AB - Data are presented which demonstrate that phasic/glycolytic muscles atrophy more than tonic/oxidative muscles in response to exogenously introduced glucocorticoids. Data are also presented demonstrating that immobilization makes a muscle unusually sensitive to glucocorticoid-induced atrophy and that remobilization of a previously immobilized muscle protects a muscle from glucocorticoid-induced atrophy. These observations are discussed within the context of the role of mechanical activity in the acquisition and maintenance of fiber-type characteristics. In addition, the available data on the glucocorticoid receptor population in skeletal muscles of various types and circumstance are reviewed within the context of the recent observations concerning the glucocorticoid induction of the enzyme glutamine synthetase in skeletal muscle. It is proposed here that atrophy is not necessarily the response of skeletal muscle to glucocorticoids. Rather, atrophy is a possible consequence of the glucocorticoid-induced increase in export of amino acid carbon from the muscle. Whether such export causes a muscle to atrophy or perhaps even hypertrophy will depend on the capacity of the muscle to sustain its free amino acid pools. Mechanical activity greatly promotes the uptake of free amino acids in skeletal muscle. Such promotion takes the form of both contraction-induced uptake and increased insulin sensitivity. Within this perspective, it is suggested that tonic muscles and remobilized muscles are protected from atrophy by exogenous glucocorticoids because their high level of mechanical activity allows them to maintain their free amino acid pools. PMID- 2199753 TI - Glucocorticoid antagonism by exercise and androgenic-anabolic steroids. AB - This work evaluated the anticatabolic capacity of androgenic-anabolic steroids and exercise (contractile activity) in inhibiting skeletal muscle atrophy associated with excessive levels of circulating glucocorticoids. With androgenic anabolic steroids, most binding studies indicate that they have very low binding specificity for the glucocorticoid receptor. Androgens may interact through their own receptor to interfere with glucocorticoid functioning at the gene level, but this remains unproven. Current literature suggests that androgens do not prevent atrophy but may retard growth suppression accompanying glucocorticoid treatment. With exercise, functional overload, resistance, and endurance types of training are capable of preventing muscle atrophy from glucocorticoids. Androgen and glucocorticoid-receptor binding and glucocorticoid-receptor activation studies have, thus far, not established that atrophy prevention is mediated through the receptor. In conclusion, the role of androgenic-anabolic steroids as glucocorticoid antagonists requires further study. Study of the effects of exercise on muscle gene expression of glucocorticoid-inducible proteins is needed to gain additional understanding of this mechanism of atrophy prevention. PMID- 2199754 TI - Effect of polyinosinic-polycytidylic acid (pl:C) on experimental mouse salmonellosis. AB - The effect of the non-specific immunomodulator polyinosinic-polycytidylic acid (pl:C) on the resistance to experimental salmonellosis was studied in the mouse. The polynucleotide was unexpectedly found to decrease the innate relative resistance of the mouse to this intracellular infection. pl:C (100 micrograms/mouse) injected 24 h before either intravenous (i.v.) or intraperitoneal (i.p.) challenge resulted in an increased intracellular rate of growth of the Salmonella in the liver, but did not affect the initial extracellular survival of the bacteria in the peritoneal cavity. By contrast, pl:C did not affect the course of mouse peritonitis caused by E. coli O18:K1, which multiplies extracellularly or that of Listeria monocytogenes, which, like Salmonella, grows intracellularly in the liver. The effect of pl:C on salmonellosis could not be explained by production of alpha or beta interferon (IFN) since it could not be demonstrated by injecting purified IFN nor could it be abolished by injecting neutralizing anti-IFN antibodies. Thus, pl:C seems to have a specific effect on salmonellosis by impairing the growth restriction of these bacteria in the liver macrophages. PMID- 2199755 TI - Relationship between intracellular survival in macrophages and pathogenicity of Streptococcus suis type 2 isolates. AB - Naturally-occurring Streptococcus suis type 2 meningitis affects pigs and man; experimental models of the disease have also been established in pigs and mice. A sustained, high-level bacteraemia is an important phase preceding the development of S. suis type 2 meningitis. The main cellular clearance mechanism for circulating bacteria is the resident hepatic and splenic macrophages. The interaction between various isolates of S. suis type 2 and murine macrophages was investigated to determine whether there were differences in the outcome of the interaction that would reflect observed differences in pathogenicity. Phagocytosed non-pathogenic isolates were killed whereas intracellular pathogenic organisms survived and replicated within phagosomes in the absence of anti-S. suis type 2 antibody and complement. The addition of anti-S. suis type 2 antibody and complement to macrophages containing ingested pathogenic organisms resulted in inactivation of the intracellular bacteria. Thus whilst the pathogenicity of S. suis type 2 isolates may be related to an ability to survive within macrophages, immunity to S. suis type 2 meningitis may result from anti-S. suis type 2 antibody preventing pathogenic organisms surviving within macrophages. PMID- 2199757 TI - Preparation of extracts and assay of ribosomal RNA maturation in Escherichia coli. PMID- 2199756 TI - Small-scale preparation of extracts from radiolabeled cells efficient in pre-mRNA splicing. PMID- 2199758 TI - Yeast suppressor mutations and transfer RNA processing. PMID- 2199759 TI - Genetic methods for study of trans-acting genes involved in processing of precursors to yeast cytoplasmic transfer RNAs. AB - All of the strategies to identify mutants defective in pre-tRNA processing have proved to be useful. However, in some of these strategies (such as inability to derepress a nonsense suppressor, correction of processing-defective substrates, and reverse genetics) only a single mutant has been isolated. This is not because the methods have proved to be inefficient, but rather because the field is still in infancy. Further work is needed to saturate the types of mutants found by each procedure. Undoubtedly, new strategies will be designed. PMID- 2199760 TI - Transfer RNA nucleotidyltransferase. PMID- 2199761 TI - Yeast extracts for transfer RNA gene transcription and processing. PMID- 2199762 TI - RNA 3'-terminal phosphate cyclase from HeLa cells. PMID- 2199763 TI - Transfer RNA splicing endonuclease from Xenopus laevis. PMID- 2199764 TI - Genetic and molecular analysis of RNA splicing in Escherichia coli. PMID- 2199765 TI - Genetic analysis of RNA splicing in yeast mitochondria. PMID- 2199766 TI - Self-splicing and enzymatic cleavage of RNA by a group I intervening sequence. PMID- 2199768 TI - Characterization of self-cleavage of viroid and virusoid RNAs. PMID- 2199767 TI - Preparation and characterization of RNase P from Escherichia coli. PMID- 2199769 TI - Preparation and fractionation of yeast splicing extract. PMID- 2199770 TI - Gene expression technology. PMID- 2199771 TI - Sequences within ribosome binding site affecting messenger RNA translatability and method to direct ribosomes to single messenger RNA species. PMID- 2199772 TI - Expression of heterologous proteins in Escherichia coli. PMID- 2199773 TI - Vector for enhanced translation of foreign genes in Escherichia coli. PMID- 2199774 TI - Minimizing proteolysis in Escherichia coli: genetic solutions. PMID- 2199775 TI - Gene fusions for purpose of expression: an introduction. PMID- 2199777 TI - Fusions to staphylococcal protein A. PMID- 2199776 TI - Design and construction of expression plasmid vectors in Escherichia coli. PMID- 2199778 TI - Expression as trpE fusion. PMID- 2199779 TI - Refolding of recombinant proteins. PMID- 2199780 TI - Heterologous gene expression in yeast. PMID- 2199781 TI - Propagation and expression of cloned genes in yeast: 2-microns circle-based vectors. PMID- 2199782 TI - Manipulating yeast genome using plasmid vectors. AB - The vectors and techniques described here enable one to manipulate the yeast genome to meet specific needs. Genes can be cloned, and the clone used to delete the wild-type gene from the chromosome, or replace it with mutant versions. Mutants derived by classical methods, such as mutagenesis of whole cells, or by reversion of a phenotype, can be cloned and analyzed in vitro. Yeast genes and foreign genes can either be inserted into autonomously replicating plasmid vectors that are reasonably stable or integrated into a yeast chromosome where they are maintained at one copy per genome. The combination of these techniques with the characterized promoter systems available in yeast make it possible to express almost any gene in yeast. Once this is achieved, the entire repertoire of yeast genetics is available to probe the function of the gene, or to engineer the expression in useful ways. PMID- 2199783 TI - Regulated GAL4 expression cassette providing controllable and high-level output from high-copy galactose promoters in yeast. PMID- 2199784 TI - Induced expression using yeast copper metallothionein promoter. PMID- 2199785 TI - High-efficiency yeast expression vectors based on the promoter of the phosphoglycerate kinase gene. PMID- 2199786 TI - Glyceraldehyde-3-phosphate dehydrogenase-derived expression cassettes for constitutive synthesis of heterologous proteins. PMID- 2199787 TI - Sequence and structural requirements for efficient translation in yeast. PMID- 2199788 TI - Promoter recognition and mRNA initiation by Escherichia coli E sigma 70. PMID- 2199789 TI - Vacuolar proteases in yeast Saccharomyces cerevisiae. PMID- 2199790 TI - Alpha-factor leader-directed secretion of heterologous proteins from yeast. PMID- 2199791 TI - Use of heterologous and homologous signal sequences for secretion of heterologous proteins from yeast. PMID- 2199793 TI - Expression of heterologous genes in mammalian cells. PMID- 2199792 TI - Isolation, characterization, and properties of Saccharomyces cerevisiae mnn mutants with nonconditional protein glycosylation defects. PMID- 2199794 TI - Use of Escherichia coli trp promoter for direct expression of proteins. PMID- 2199795 TI - Optimizing cell and culture environment for production of recombinant proteins. PMID- 2199796 TI - Use of T7 RNA polymerase to direct expression of cloned genes. PMID- 2199797 TI - High-level translation initiation. PMID- 2199798 TI - Enhanced translational efficiency with two-cistron expression system. PMID- 2199799 TI - Measles--eradication or procrastination? PMID- 2199800 TI - Inhaled corticosteroids in asthma. PMID- 2199801 TI - Comparison of simvastatin and cholestyramine in the treatment of primary hypercholesterolaemia. AB - The effects of simvastatin, a competitive inhibitor of the enzyme 3-hydroxy-3 methylglutaryl-coenzyme A reductase, on plasma lipid levels were compared with those of the bile acid sequestrant cholestyramine in a randomized parallel study of 60 subjects with primary hypercholesterolaemia. After a 12-week direct comparison period 37 subjects with inadequate cholesterol reduction received a combination of both drugs and all subjects were followed for a further 40 weeks. Simvastatin was more effective than cholestyramine in lowering total and LDL cholesterol levels and the LDL/HDL ratio (-31.7% v. -19.7% [P less than 0.01], 41.0% v. -31.8% [P less than 0.05] and -46.7% v. -33.6% [P less than 0.01], respectively at Week 12). Only simvastatin significantly increased the HDL cholesterol concentration (+13.3% [P less than 0.01] v. +6.4%). Cholestyramine increased plasma triglyceride levels by 37.5% (P less than 0.01) whereas simvastatin caused a slight non-significant reduction. Combined therapy produced a further decrease in total and LDL cholesterol levels, and in the LDL/HDL ratio, which was sustained for the duration of the study. Simvastatin was better tolerated than cholestyramine (P less than 0.01), and combining the two drugs enhanced efficacy without increasing the frequency of side effects. PMID- 2199802 TI - Effect of a single dose (3 mg/kg) of diethylcarbamazine on Wuchereria bancrofti var pacifica microfilaraemia. PMID- 2199803 TI - Voluntary HIV antibody testing among STD clinic patients: a pilot study. AB - A pilot study was conducted with the aim of measuring the acceptability of voluntary testing for human immunodeficiency virus (HIV) antibody among patients attending sexually transmissible disease (STD) clinics. Three STD clinics, two public and one private, participated in the study which was conducted over a three-month period beginning in November 1988. For each patient attending the clinics, sex, date of birth, HIV transmission category and previous HIV test result were recorded. Patients who did not request the HIV antibody test were offered testing. Of the 2356 patients who were included in the analyses, 784 (34%) requested testing. For almost all patients (97%) who requested testing, a serum sample was collected and testing completed. Approximately half (55%) of those patients who were offered the test accepted testing. Overall, 70% of patients completed HIV antibody testing. Of the major transmission categories, the acceptance rate for those offered the test was lowest among homosexual men (45%), who also had the highest rate of HIV antibody seropositivity (11%) among those tested. Of patients who reported themselves to be HIV antibody seronegative prior to the pilot study, 78% were retested during the study and seven had a positive test for HIV antibody. We conclude that voluntary HIV antibody testing is acceptable in both public and private STD clinic settings, although a substantial amount of additional resources would need to be allocated to counselling if voluntary testing is to be introduced on a routine basis. PMID- 2199804 TI - Proarrhythmic effects of antiarrhythmic drugs. AB - Drugs that are described as antiarrhythmic drugs may actually aggravate arrhythmia in several ways and these are termed proarrhythmic effects. The most common type of proarrhythmia is a paradoxical increase in the frequency of episodes of the target arrhythmia. This type of effect had not been suspected until recently and has not been widely publicized. It is a phenomenon common to all antiarrhythmic drugs when they are used to treat arrhythmias based on a re entrant mechanism (the most common mechanism of clinical arrhythmias). Different drugs vary in their tendency to produce this type of proarrhythmic response. These differences are explicable in terms of the relative effects of the drugs on refractoriness and conduction times in the re-entrant circuit. Proarrhythmic effects are most important in the treatment of ventricular tachycardias because recurrences are often fatal. Proarrhythmic effects on ventricular tachycardia can now be predicted at electrophysiological study before commencement of long-term therapy, and potentially dangerous treatment can be avoided. The key to proper treatment to proarrhythmia is to recognize that it is a drug-induced problem and to withdraw the offending drug. PMID- 2199805 TI - [Pathology caused by microdoses of chemical substances]. AB - Improvement in environmental conditions in industry is producing a progressive reduction in the dose of absorbed substances. This has repercussions on the work of the occupational health physician, who now has to face a new set of problems, problems which at the same time offer occasions for further research in risk assessment of chemical agents. The most obvious finding, which has perhaps been handled more systematically, concerns the change in occupational diseases, whence the need to extend designs and protocols of health surveillance. The expected effects of occupational exposure to low doses of a chemical fall within the category of what may be defined as long-term effects, carcinogenic effects and, above all, effects involving systems or apparatuses that are sensitive to low doses but over long periods, such as, for example, the immune and the reproductive systems. This new situation than has repercussions on biological monitoring: in the first place on the problem of setting reference values and on the study and control of confounding factors; secondly, on the predictivity of the biological indicators used. In some cases, in fact, the indicators of dose that the occupational health physician has learnt to use and on which his approach to prevention his based, proved to be no longer predictive in such new exposure situations. PMID- 2199806 TI - [The AMES test in environmental and occupational medicine]. AB - The authors review the use of the gene mutation test on Salmonella typhimurium, better known as the Ames test, in environmental and occupational health. This test, which was originally intended as a predictive test of the carcinogenicity of chemical substances, has been widely applied in in vitro screening of complex mixtures of substances present in the environment and in the biological monitoring of high risk populations. Data are reported on the main environmental exposures that were positive with the Ames test and it is stressed how this biological assay has contributed to the identification of new classes of genotoxic compounds (nitropyrenes, mutagen X). The Ames test performed on extracts of human urine was used to study exposure to carcinogenic substances in the working environment. Many occupational exposures can cause an increase in mutagenic activity in the exposed subjects (cytostatic drugs, rubber manufacture, polycyclic aromatic hydrocarbons). It is recommended to restrict the use of the urinary mutagenesis test to group studies and carefully check confounding factors (e.g., smoking and diet). PMID- 2199807 TI - [Mutagen activity of barium chloride in Salmonella typhimurium]. AB - Barium chloride, which is an important industrial chemical used in pigments, lacquers, dyes, glass and pesticide production, leather tanning and cloth dying, was tested on Salmonella typhimurium (TA 1535, TA 1537, TA 1538, TA 97, TA 98, TA 100) with the reverse mutation test, with and without metabolic activation, to assess its possible genotoxic effects and any possible action with respect to standard mutagens (sodium azide, 9-aminoacridine, 2-nitrofluorene, mitomycine-C, 2 aminoacridine). Using the platelet incorporation technique, barium chloride at various progressive concentrations gave negative results under the experimental conditions of the study. PMID- 2199808 TI - [Determination of blood bile acids using high pressure liquid chromatography: comparison of chromatographic, enzymatic and immunoenzymatic methods]. AB - A method has been developed for measuring serum conjugated bile acids by HPLC. Serum samples, to which the internal standard is added, are purified by a solid phase procedure and injected on a reverse phase C18 column. Elution is accomplished by means of a flow gradient and peaks are detected at 198 nm. The detection limit ranges between 0.05 and 0.20 mumol/l for different analytes; between-day precision (CV 5.8%), working linear range (up to 50 mumol/l) and recovery (87%) were established. Comparison of the results obtained with HPLC, enzymatic and immuno-enzymatic methods gave high correlation coefficients. The method was applied for diagnostic purpose to a group of subjects suffering from various liver diseases. Also, 106 healthy workers, not occupationally exposed to known or potentially hepatotoxic agents, were studied in order to establish reference values for use in biological monitoring of chronic low level exposure to solvents. The method has the advantage of a more simple procedure compared to previously reported HPLC methods and appears to be well suited for routine use in toxicological and clinical test laboratories. PMID- 2199809 TI - Ketorolac tromethamine. PMID- 2199811 TI - [A case of congenital multiple arthrogryposis. Considerations]. AB - The paper describes the diagnosis, clinical, anatomopathological and etiopathogenetic aspects of a case of congenital multiple arthrogryposis. The importance of the dialogue between the obstetrician and the parents is underlined in terms of the latters' psychological preparation. The obstetrician must also prepare for an atraumatic delivery, in addition to planning the treatment protocol for the neonate. PMID- 2199812 TI - [Tumors and the histogenesis of Schwann cells of maxillofacial competence]. AB - After a brief review of published data relating to the clinical and anatomicopathological characteristics and therapeutic problems of tumours deriving from the nerve sheaths of the oromaxillofacial area, the paper reports 13 cases of these neoplasias observed from 1975 to 1988 in the maxillofacial surgery ward of the Dentistry Clinic at the University of Turin. The group include 6 schwannomas (neurinomas), 6 neurofibromas and 1 malignant schwannoma. Clinical symptoms and methods of diagnosis are described. PMID- 2199813 TI - [A longitudinal clinical study of the efficacy of tetracyclines combined with root planing in patients with periodontal disease]. AB - A retrospective longitudinal study was performed to assess the effectiveness of tetracycline therapy associated with root planing compared with root planing alone in patients affected by medium to severe periodontal disease. From an analysis of results it appeared that the combined therapy was generally more successful, even though statistical significance was only achieved in cases of healing angular bone lesions. In conclusion, larger studies should be carried out to contribute to broaden the spectrum of indications for the use of antibiotic therapy in periodontal disease in adults. PMID- 2199814 TI - [The role of Streptococcus mutans in human caries]. AB - Definite proof has been found that S. mutans, and probably S. sobrinus and lactobacilli, are responsible for caries in man. The aciduria of S. mutans encourages the selection inside the plaque and is directly responsible for its cariogenicity. Other aciduric species, as S. sobrinus, cause caries on the smooth surface of the tooth, where the principal causes of the rampant caries reside. If during the eruption of the tooth the fissures become colonized in depth by S. mutans, the development of caries becomes a highly probable event. Instead, if the colonization of the tooth by S. mutans takes place after the fissure depth have been occupied by other microbic species not cariogenic, it is probable that the caries will not manifest or will appear in a less severe form. In conclusion, the knowledge already acquired on the ecology of S. mutans and the mechanism of cariogenesis clearly indicate that all factors that interfere with the colonization of the tooth by S. mutans can greatly reduce the incidence of caries in man. PMID- 2199815 TI - A soybean gene encoding delta 1-pyrroline-5-carboxylate reductase was isolated by functional complementation in Escherichia coli and is found to be osmoregulated. AB - We have isolated several cDNA clones encoding delta 1-pyrroline-5-carboxylate reductase (P5CR, L-proline: NAD(P)+ 5-oxidoreductase, EC 1.5.1.2) which catalyzes the terminal step in proline biosynthesis, by direct complementation of a proC mutation in Escherichia coli with an expression library of soybean root nodule cDNA. The library was constructed in the lambda ZapII vector, converted to a plasmid library by in vivo excision of recombinant pBluescript phagemids, and used for transformation of the E. coli mutant. Complementing plasmids contained inserts of about 1.2 kb which hybridized to a 1.3 kb RNA transcript in nodules, uninfected roots and leaves. DNA sequence analysis of one full length cDNA clone showed that it encodes a 28 586 Mr polypeptide with 39% amino acid identity to the E. coli P5CR sequence. Genomic analysis showed that there are two to three copies of the P5CR gene in the soybean genome. The steady-state level of P5CR mRNA in root nodules was twice as high as in uninfected roots and about five times higher than in leaves. Subjecting young seedlings to osmotic stress by watering with 400 mM NaCl resulted in an almost six-fold increase in the level of root P5CR mRNA, suggesting that this gene may be osmoregulated. PMID- 2199816 TI - Induction of -2 frameshift mutations within alternating GC sequences by carcinogens that bind to the C8 position of guanine residues: development of a specific mutation assay. AB - Using a forward mutation assay we have previously found that N-2 acetylaminofluorene (AAF), a strong chemical carcinogen, induces a majority of frameshift mutations located at specific sequences called mutation hot spots. Among these hot spot sequences, the NarI sequence (GGCGCC), is specific for -2 frameshifts (GGCGCC)----GGCC). Interestingly, these frameshift mutations occur independently of a functional umuDC locus. Being interested in elucidating this mutation pathway we have developed a reversion assay that is specific for this class of mutations. The assay is based on the reversion of a +2 frameshift mutant of plasmid pBR322 from tetracycline sensitivity to tetracycline resistance. It is shown that only "true" reversion events lead to tetracycline resistance. The carcinogen AAF induces this reversion event at a frequency that is increased four to fivefold over the background frequency. A series of chemical carcinogens which, like AAF, bind covalently to the C8 position of guanine, are compared for their efficiency to induce this specific mutation event. Large variations in the mutagenic efficiency of these chemicals are observed and discussed in terms of the anti/syn conformation of the carcinogen-modified guanine residue. Based on this test, we describe a convenient spot assay that this presently used in our laboratory to isolate Escherichia coli mutants affected in this mutation pathway. PMID- 2199817 TI - Repair of alkylation damage in Saccharomyces cerevisiae. AB - Repair of methylated bases in Saccharomyces cerevisiae was measured by two methods: in vitro in cell extracts, and in vivo, by determining the loss of methylated bases from yeast DNA after treatment of stationary cultures with [3H] N-methyl-N'-nitro-N-nitrosoguanidine. Whereas no repair activity could be detected by the in vitro method, the methylated bases were removed in vivo very efficiently. These contradictory results of in vitro and in vivo repair measurements suggest that either the repair enzymes of yeast are sufficiently different from those of bacteria and mammalian cells that they are not active in the in vitro assay, or that methylated bases are repaired in yeast by a different pathway. PMID- 2199819 TI - Analysis of a mutated phage T6 receptor protein of Escherichia coli K 12. AB - The tsx-206 allele encodes an altered Tsx protein, Tsx-206, that can no longer function as the T6 receptor. We show here that this allele also confers resistance to the Tsx-specific phages H1, H3, H8, K9, K18 and Ox1 but not to colicin K. The Tsx-206 protein still mediates the efficient permeation of deoxyadenosine across the outer membrane at low substrate concentration. A host range mutant of phage T6, T6h3.1, was isolated which can use both the Tsx-206 and the Tsx wild-type protein as its receptor. Cloning and DNA sequence analysis of the tsx-206 allele showed that the phage resistant phenotype was associated with an Asn to Tyr substitution at position 254 of the 272-residue Tsx protein. PMID- 2199818 TI - Export incompatibility of N-terminal basic residues in a mature polypeptide of Escherichia coli can be alleviated by optimising the signal peptide. AB - Export of the outer membrane protein, OmpA, across the cytoplasmic membrane of Escherichia coli was severely inhibited by the presence of two, three, four or six additional basic residues at the N-terminus of the mature polypeptide, but not by three similarly positioned acidic residues. Because a few bacterial proteins do possess basic residues close to the leader peptidase cleavage site and because the type of inhibition described here could pose problems in the construction of hybrid secretory proteins, we also studied means of alleviating this form of export incompatibility. Inhibition was abolished when basic residues were preceded by acidic ones. Also, the processing rates of the mutants with two or six basic residues could be partially restored by increasing the length of the hydrophobic core of the signal peptide. Taking this as a precedent, it is suggested that the structure of the signal peptide is an important feature for maintenance of a reasonable rate of translocation of those exported proteins which possess basic residue(s) at the N-terminus of the mature polypeptide. PMID- 2199820 TI - Protein H--a novel IgG binding bacterial protein. AB - Forty-eight group A streptococcal strains of different M types were screened for binding of human radiolabeled IgG. Three of the strains bound more than 80% of the added radioactivity and one of them, an M protein type 1 strain designated AP1, was selected for further analysis. Attempts were made to solubilize the IgG binding bacterial molecule, and small amounts of an IgG binding protein with a mol. wt of 40 kDa could be solubilized with mutanolysin, a muramolytic agent. The gene encoding this streptococcal protein was cloned and expressed in E. coli, and the E. coli-produced protein was purified in a single step by affinity chromatography on IgG-Sepharose. When tested with IgGs from different species, the molecule was found to bind human IgG almost exclusively. The N-terminal amino acid sequence was determined and showed no homology with previously isolated Ig binding proteins, and the name protein H (as in human IgG) is suggested for this novel Ig binding bacterial protein. Protein H showed preferential affinity for heavy chains and Fc fragments of human IgG, and did not bind Ig light chains. The affinity constant, determined by Scatchard plots, between protein H and human polyclonal IgG was 1.6 x 10(9). No binding was observed between protein H and IgM, IgA, IgD, or IgE. Finally, when tested against several additional proteins and human plasma, protein H only showed weak binding to alpha 2-macroglobulin, a proteinase inhibitor. PMID- 2199821 TI - A comparison of alkaline phosphatase and radiolabelled gene probes with bioassays for enterotoxigenic Escherichia coli. AB - Alkaline phosphatase-conjugated oligonucleotide probes (APO), 32P-labelled oligonucleotide (RO) and cloned polynucleotide (RP) probes were evaluated for their ability to detect enterotoxigenic Escherichia coli (ETEC) as defined by bioassay. These three sets of probes were applied to 301 E. coli strains that had previously been defined by the Y1 adrenal cell assay for heat-labile enterotoxin (LT) and the infant mouse assay for heat-stable enterotoxin (ST). The correlation of the APO probe for LT with the bioassay was 98% with five discrepancies and a positive predictive value (PPV) of 100%. For the APO/ST probe the correlation with the bioassay was 98% with seven discrepancies and a PPV of 96%. The correlation of the RO probe for LT was 99% with four discrepancies and a PPV of 100%, while the overall correlation for the two RO/ST probes was 97% with eight discrepancies and a PPV of 97%. For the RP probes, the correlation for LT was 99% with four discrepancies and a PPV of 100% and for ST was 98% with seven discrepancies and a PPV of 98%. These findings suggest that the APO probes were as sensitive as the RO and RP probes in detecting ETEC by colony hybridization and could be a practical alternative to bioassays and radiolabelled probes for ETEC since they do not require expensive equipment or extensive technical training. PMID- 2199822 TI - Specific identification of Mycobacterium leprae by the polymerase chain reaction. AB - Oligonucleotide primers have been used to amplify DNA regions of the M. leprae genome by the polymerase chain reaction. A first set of primers, PLp1 and PLp2, identifies a specific 386 bp DNA fragment located in the gene coding for the 65 kDa antigen of M. leprae. A second pair of primers, targetted to the same gene, leads to the amplification of a 154 bp DNA piece conserved in mycobacteria. Primers PLp1 and PLp2 discriminate the pathogenic species from other mycobacteria, detect down to 40 bacilli, and constitute potentially useful tools for the identification of M. leprae in clinical specimens. PMID- 2199823 TI - A DNA hybridization test for detection of Bordetella in nasopharyngeal specimens. AB - A cloned Bam H1 fragment of genomic Bordetella pertussis DNA which recognized a frequently repeated sequence in the genome of B. pertussis was used as a probe in a DNA hybridization assay for the detection of Bordetella. Extensive studies on cross-reactivity were carried out in standardized strains and in cultured swab specimens from patients without suspected pertussis. Hybridizations of cultured clinical specimens from 142 patients with suspected pertussis were in complete agreement with the standard identification methods. The recovery rate of B. pertussis from nasopharyngeal swabs was less than 50%. Therefore the possibility to detect low numbers of B. pertussis in solution (nasopharyngeal aspirates) was investigated. The detection limit of direct hybridization by dot-blot technique was 5 x 10(3)-10(4) B. pertussis. Culturing bacteria on membranes placed on agar plates prior to hybridization showed that the detection limit could be lowered to 10(4), 10(2), and 10(1) cfu after 1, 2 and 3 days' culture, respectively. DNA hybridization under these conditions was found to be sufficiently sensitive and specific for further evaluation in clinical specimens for diagnosis of pertussis. PMID- 2199824 TI - [The incidence of Hodgkin's disease: characteristics of its appearance, histological types]. AB - In study of lymphogranulomatosis (LGM), epidemiological surveys and so-called "Rye Classification" for separation of histological types significantly helped to get to know the background and circumscription of etiopathogenesis of the disease. In her paper author analysed histological distribution of types, distribution of sex of patients, their average age, age-specific incidence of disease in LGM registered cases of ten years in Malignant Lymphoma Reference Centre. On basis of rate of histological types, compared to each other, and of number of LGM cases in childhood, it can be established that in MLRC incidence of LGM corresponded to so-called intermediary types (II), namely it showed characteristics of distribution between developed and economically underdeveloped countries. Age-specific incidence of 716 LGM cases studied by author was ot bimodal character, age-specific incidence of nodular sclerosis was different from it. Presumably this fact and different nature of LGMs of other type or its different pathogenesis are in the background. PMID- 2199825 TI - [Optimization of expression of hepatitis B surface antigen gene in yeasts]. AB - A series of recombinant plasmids has been constructed for expression of the hepatitis B viral surface antigen gene (HBsAg) under the control of the regulatory elements of the yeast acidic phosphatase gene (PHO5). The obtained plasmids possess the high mitotic and structural stability in the transformant yeast cells. The effect of different structural modifications of the vector on the level of HBsAg synthesis in yeasts has been studied. Optimal construction devoid of the bacterial DNA sequences and pre-S region has been selected. PMID- 2199826 TI - [Synthesis and secretion of recombinant protein--the product of v-sis oncogene in Saccharomyces cerevisiae cells]. AB - The recombinant plasmid DNA YEp secl-v-sis was constructed. This plasmid was able to code for the synthesis and secretion into the cultural medium of the protein product of oncogene v-sis. Transcription, copy number and stability of the plasmid DNA were studied under the conditions of galactose induction. The v-sis protein was determined by gel electrophoresis and immunoblotting methods and assayed for cell-proliferation activity in the mammalian cell culture. PMID- 2199827 TI - [Mutational analysis of the starch utilization system in the yeast Saccharomyces cerevisiae]. AB - Seven mutants of Saccharomyces cerevisiae deficient in production of extracellular glucoamylase have been analyzed. For each of the seven a monogenic pattern of inheriting the mutant phenotype has been observed. The mutations have been shown to map within five different genetic loci, three independent mutations affecting the STA2 locus and the other four residing in four formerly unidentified genes. As expected, the sta2 mutants recover the wild phenotype when transformed with a STA2-bearing multicopy plasmid. Such reversion has also been observed for the transformed stall mutant. Unlike the others, the sta16 mutant is unable to secrete heterologous alpha-amylase encoded by a plasmid-borne DNA fragment. All the mutants have a moderately reduced ability to secrete the invertase and acid phosphatase. PMID- 2199828 TI - [Fusion of Erwinia chrysanthemi spheroplasts in an electric fields]. AB - A new approach has been elaborated for electrofusion of Erwinia chrysanthemi spheroplasts. The new approach consists of superimposition of high voltage impulses on the pellet of tightly contacting cells in the course of centrifugation. The mixture of spheroplasts of two genetically marked strains was placed into the special centrifuge chambers and spinned for 15 min at 2500 g to get a compressed pellet between chamber electrodes. Three successive pulses of 6.6 kv/cm amplitude and 30 microseconds duration were applied to spheroplast pellet during centrifugation. Fusion products were viable and after plating on the surface of hypertonic medium regenerated to the rod forms. As a result, the hybrid clones carrying the markers of both parents were isolated. PMID- 2199829 TI - K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung. AB - BACKGROUND: The capability of activated oncogenes to induce malignant transformation of immortalized cells in vitro has suggested that they have a similar role in the pathogenesis of human tumors. We previously found that activation of the K-ras oncogene by a point mutation in codon 12 occurs in about one third of human lung adenocarcinomas. METHODS: We studied the clinical importance of this oncogene-activation in 69 patients with lung adenocarcinoma in whom complete resection of the tumor was possible. The polymerase chain reaction was used to amplify ras-specific sequences of DNA isolated from frozen or paraffin-embedded tumor samples. Ras point mutations were subsequently detected and classified with the use of mutation-specific oligonucleotide probes. RESULTS: Nineteen of the tumors harbored a point mutation in codon 12 of the K-ras oncogene. There was no association between the K-ras point mutation and the age at diagnosis, sex, or presence of previous or concurrent neoplasms. Tumors positive for K-ras point mutations tended to be smaller and less differentiated than those without mutations. The K-ras codon-12 point mutation was a strong (and unfavorable) prognostic factor: 12 of the 19 patients with K-ras point-mutation positive tumors died during the follow-up period, as compared with 16 of the 50 patients with no mutation in the K-ras oncogene (P = 0.002). This difference in prognosis was also reflected in the duration of disease-free survival (P = 0.038) and in the number of deaths due to cancer (P less than 0.001). CONCLUSIONS: The presence of K-ras point mutations defines a subgroup of patients with lung adenocarcinoma in whom the prognosis is very poor and disease-free survival is not usually long despite radical resection and a small tumor load. PMID- 2199830 TI - Amelioration of proximal renal tubular dysfunction in type I glycogen storage disease with dietary therapy. PMID- 2199831 TI - Functional disorders of the esophagus: current concepts and diagnoses. PMID- 2199832 TI - Structural studies on native and chemically modified storage proteins from rapeseed (Brassica napus L.) and related plant proteins. AB - Recent data on the structure and chemical modification of the two main storage proteins of rapeseed, the high-molecular mass 12 S globulin and the low-molecular mass 2 S protein (napin) are summarized and compared with those of related seed proteins. The 12 S globulin is built up of six subunits forming a quaternary structure which can be approximated by the model of a trigonal antiprism. The subunits, composed of a larger and a smaller polypeptide chain each, have a two domain structure which is typical for all related plant proteins. These are characterized by a sedimentation coefficient of 11-13 S, a molecular mass of 300,000-360,000 g/mol and a high percentage of beta-sheet conformation. Increasing succinylation results in a step-by-step dissociation up to the subunits and to an unfolding of the latter at a critical level of modification amounting to 60-70%. These structural changes affect the functional properties remarkably. The napin fraction comprises a group of closely related and highly basic proteins with molecular masses of 12,000-14,000 g/mol, a high content of sulphur-containing amino acids and rich in helical conformation. They are built up of a larger and a smaller disulphide bridged polypeptide chain. Acylation does not abolish the secondary or tertiary structure which are stabilized by inter- and intrachain disulphide bonds. Acylation results, however, in a stabilization of the protein against heat-induced aggregation. PMID- 2199833 TI - Planning hospitals. Part 1: Stages of a project. PMID- 2199834 TI - AIDS scan. WHO issues new estimates of HIV/AIDS by the year 2000. PMID- 2199835 TI - Waking up to an OTA, OIG morning. Reports show need for accurate administrative cost survey. Office of Technology Assessment. Office of the Inspector General. PMID- 2199836 TI - The historical encipher. PMID- 2199837 TI - Identifying clinical nursing research priorities. AB - This paper describes a project conducted by a nursing research committee to identify and prioritize nursing research questions or topics that are most significant to the welfare of patients at a Southern university hospital. Ninety seven nurses representing clinical staff, administration, and education were invited to participate in three rounds using the Delphi survey technique. Group consensus was reached on priority areas for nursing research at this particular institution. The purpose of this article is to outline the process of developing the project and discuss recommendations resulting from the survey. PMID- 2199838 TI - Health services research in nursing: current status and future directions. AB - To assess the current status of health services research in nursing, 113 studies reported between 1980 and 1989 were reviewed. Identified gaps in this research included comprehensive cost-benefit and cost-effectiveness analyses, effects of technology on patient care, evaluations of information systems, evaluations of innovative care delivery approaches, and studies of ethical issues related to the use of scarce resources. PMID- 2199839 TI - Neuronal basis of the parkinsonian resting tremor: a hypothesis and its implications for treatment. PMID- 2199840 TI - Enhanced dopamine receptor activation in accumbens and frontal cortex has opposite effects on medial forebrain bundle self-stimulation. AB - This study was undertaken to investigate the effects of activating dopamine receptors in accumbens and prefrontal cortex on self-stimulation behavior in the medial forebrain bundle. The experiments were carried out in rats chronically implanted with one stimulating electrode in medial forebrain bundle and two bilaterally-placed cannulas for giving injections into accumbens or prefrontal cortex. After completion of training, animals classified as responders and non responders were given drug tests. The non-responders were tested to determine the effects of the treatment on motor activity. The self-stimulation task involved the depression of a lever to obtain a stimulus of 0.25 s duration, 60 Hz sine waves applied to the medial forebrain bundle. Dopamine receptor activation in accumbens or prefrontal cortex was induced with bilateral injections in these structures of a mixture containing 5 mg dopamine, 10 mg d-amphetamine sulfate and 5 mg pargyline mixed in 0.5 ml saline containing 0.1% ascorbic acid (dopamine + d amphetamine sulfate + pargyline, the cocktail). Each injection was of 2 microliters/side, yielding a concentration of 20 micrograms of dopamine, 40 micrograms of d-amphetamine sulfate and 20 micrograms of pargyline/injection. The bilateral injections were given immediately before the self-stimulation session which lasted 12 h, starting in late afternoon. The effects of saline containing the ascorbate were determined in control sessions. Saline injected bilaterally in accumbens or prefrontal cortex of self-stimulators or non-self-stimulators had no effects on the response-rate of self-stimulators or on the gross motor activity of non-responders. In contrast, the cocktail of dopamine + d-amphetamine sulfate + pargyline injected in accumbens of self-stimulators induced a complex response which included first a facilitation, then a prolonged suppression and then again one or two episodes of facilitation interspersed with periods of suppression of self-stimulation and then a return to baseline rats. The same cocktail of dopamine + d-amphetamine sulfate + pargyline injected bilaterally in accumbens of non-self-stimulators resulted also in a complex response including as a first component a facilitation of responding, but the complex effect was of shorter duration and lower magnitude, never raising the rate of lever-pressing to levels meeting self-stimulation criteria. The same cocktail of dopamine + d-amphetamine sulfate + pargyline injected in prefrontal cortex of self-stimulators simply attenuated or suppressed responding, and the effect lasted for most of the session. The same effect was seen in non-self-stimulators indicating a decrease in gross motor activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2199841 TI - Calbindin D-28k and parvalbumin in the rat nervous system. AB - This paper describes the distribution of structures stained with mono- and polyclonal antibodies to the calcium-binding proteins calbindin D-28k and parvalbumin in the nervous system of adult rats. As a general characterization it can be stated that calbindin antibodies mainly label cells with thin, unmyelinated axons projecting in a diffuse manner. On the other hand, parvalbumin mostly occurs in cells with thick, myelinated axons and restricted, focused projection fields. The distinctive staining with antibodies against these two proteins can be observed throughout the nervous system. Calbindin D-28k is primarily associated with long-axon neurons (Golgi type I cells) exemplified by thalamic projection neurons, strionigral neurons, nucleus basalis Meynert neurons, cerebellar Purkinje cells, large spinal-, retinal-, cochlear- and vestibular ganglion cells. Calbindin D-28k occurs in all major pathways of the limbic system with the exception of the fornix. Calbindin D-28k is, however, also found in some short-axon cells (Golgi type II), represented by spinal cord interneurons in layer II and interneurons of the cerebral cortex. It is also detectable in some ependymal cells and abundantly occurs in vegetative centres of the hypothalamus. The "paracrine core" of the nervous system and its adjunct (1985, Nieuwenhuys, Chemoarchitecture of the Brain. Springer, Berlin) is very rich in calbindin D-28k. The distribution of calbindin D-28k-positive neurons is very similar to that of the dihydroperydine subtype of calcium channels. Most of the cells containing calbindin D-28k are vulnerable to neurodegenerative processes. Parvalbumin-immunoreactive neurons have a different, and mostly complementary distribution compared with those which react with calbindin D-28k antisera, but in a few cases (Purkinje cells of the cerebellum, spinal ganglion neurons), both calcium-binding proteins co-exist in the same neuron. Many parvalbumin-immunoreactive cells in the central nervous system are interneurons (Golgi type II) and, to a lesser extent, long-axon cells (Golgi type I), whereas conditions are vice versa in the peripheral nervous system. Intrinsic parvalbuminic neurons are prominent in the cerebral cortex, hippocampus, cerebellar cortex and spinal cord. Long-axon parvalbumin-immunoreactive neurons are, for example, the Purkinje cells, neurons of the thalamic reticular nucleus, globus pallidus, substantia nigra (pars reticulata) and a subpopulation among large spinal-, retinal-, cochlear- and vestibular ganglion cells. Parvalbumin is rich in cranial nerve nuclei related to eye movements. In addition to nervous elements, parvalbumin immunoreactivity occurs in a few ependymal cells and in some pillar cells of the organ of Corti.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2199842 TI - Free radical generation during brief period of cerebral ischemia may trigger delayed neuronal death. AB - We investigated the pathogenic role of free radical formation in ischemic neuronal death using radical scavenger, superoxide dismutase. Cerebral ischemia was produced in the gerbil by bilateral common carotid occlusion for 5 min, which consistently resulted in delayed neuronal death in the CA1 region of the hippocampus. The effects of free superoxide dismutase and a derivatized superoxide dismutase, pyran copolymer conjugated superoxide dismutase, on early ischemic damages, detected sensitively by the immunohistochemical reaction for microtubule associated protein 2, and a subsequent delayed neuronal death after restoration of blood flow were investigated. Preischemic treatment by pyran conjugated superoxide dismutase showed clear protective effects against both the neuronal damages detected by immunohistochemistry after 5 min ischemia and the delayed neuronal necrosis after one week of recovery, although no clear beneficial effects were observed when this drug was administered just before the recirculation or free superoxide dismutase was used. These results strongly suggest that free radical generation during brief period of ischemia plays a pivotal role in triggering the ischemic neuronal damages causing delayed neuronal death at the selectively vulnerable areas of the brain. PMID- 2199843 TI - Trophic effects of insulin-like growth factor-I on fetal rat hypothalamic cells in culture. AB - The hypothesis that insulin-like growth factor-I is a trophic factor for primary fetal rat hypothalamic cells was tested, since we previously reported a potent mitogenic effect of this peptide on virally-transformed hypothalamic cells. It was found that insulin-like growth factor-I produced significant and dose dependent increases in the survival of fetal hypothalamic neurons in primary mixed glial/neuronal cultures. By 48 h in vitro, cultures treated with insulin like growth factor-I (6 nM) had twice as many neurite-bearing cells as controls, while by day 15 a five-fold difference was present. The peptide was similarly active in promoting neuronal survival in neuron-enriched (98% neurons) hypothalamic cultures. Mixed hypothalamic cultures had specific binding sites for insulin-like growth factor-I. In addition, the neurons grown in the presence of insulin-like growth factor-I had a more differentiated morphology and had significantly higher levels of protein kinase C, an enzyme that increases during neurite formation and synaptogenesis. Finally, glial-enriched cultures (greater than 99% glial cells) obtained from the fetal hypothalamus showed increased [3H]thymidine incorporation in response to insulin-like growth factor-I. These results further support the contention that insulin-like growth factor-I is a neurotrophic factor and suggest that it may participate in the normal development of the hypothalamus by increasing neuronal survival/differentiation and stimulating glial growth. PMID- 2199844 TI - Cellular localization of carnosine-like and anserine-like immunoreactivities in rodent and avian central nervous system. AB - Aminoacylhistidine dipeptides are present in the nervous tissue of many species. The olfactory mucosa and bulb of many vertebrates are rich in carnosine (beta alanyl-L-histidine). Two related dipeptides homocarnosine (gamma-aminobutyryl-L histidine) and anserine (beta-alanyl-N-methyl-L-histidine) are present in the CNS of mammals and birds, respectively. This manuscript describes the production, characterization and use in immunolocalization studies of antisera directed against carnosine and anserine. The anserine antiserum is highly specific for anserine while the carnosine antiserum cross-reacts with all three dipeptides. The differential specificity of the antisera, coupled with chemical characterization of the dipeptide composition of various brain regions, has permitted assignment of the cellular localization of the various dipeptides. Immunocytochemical localization of anserine has not been previously reported. Carnosine immunoreactivity in the olfactory system is restricted to the mature neurons in the olfactory mucosa, their axons and synaptic terminations in the glomerular layer of the olfactory bulb. Similar reactivity is seen in the accessory olfactory system. Astrocytes and cerebellar Bergmann glia seem to account for all the non-olfactory carnosine-like immunoreactive staining in the rodent brain. In contrast, in the avian CNS where anserine is chemically abundant, anserine-like immunoreactivity is widespread and apparently exclusively associated with glial cells. Thus, the olfactory receptor neurons appear to be the only neuronal population that expresses carnosine. Elsewhere in the CNS the aminoacylhistidine dipeptides are associated with various populations of glia. PMID- 2199845 TI - Locomotor recovery in spinal-transected lamprey: regenerated spinal coordinating neurons and mechanosensory inputs couple locomotor activity across a spinal lesion. AB - Larval lampreys recover locomotor function several weeks after receiving complete spinal transections. In behaviorally recovered whole-animals, the phase-coupling of locomotor activity across a lesion was similar to that observed along the body in normal, unlesioned lampreys. Two factors were found to contribute to recovery of locomotor coupling above and below a spinal transection. Firstly, under in vitro conditions regenerated spinal coordinating neurons could couple brainstem evoked locomotor activity above and below a lesion in the absence of mechanosensory inputs. Secondly, in whole-animals mechanosensory inputs were capable of coupling locomotor activity across an acute, mid-body spinal transection in the absence of direct neural coupling through spinal coordinating neurons. Since neither regenerated coordinating neurons nor mechanosensory inputs resulted in phase-lags that were as stable as those observed in recovered whole animals, presumably both mechanisms contribute significantly to the restoration of locomotor coupling across a healed spinal lesion. PMID- 2199846 TI - Neonatal hypothyroidism induces striatal dopaminergic dysfunction. AB - Oral administration of the antithyroid drug methimazole (50 mg/kg per day) to rats during the last six days of pregnancy, and subsequent daily s.c. injection of methimazole (20-30 mg/kg) to their pups from birth to postnatal day 30 provoked hormonal and somatic alterations resembling (with all caution to any association between rodent and human data) those of congenital hypothyroidism. The steady-state concentrations of striatal dopamine were similar in hypothyroid and euthyroid, 32-day-old rats, while the levels of the dopamine metabolites 3,4 dihydroxyphenylacetic and homovanillic acids were markedly decreased in hypothyroidism. The results of this and our earlier study [Vaccari A. and Gessa G. L. (1989) Neurochem. Res. 14, 949-955] show that the maximal synaptosomal uptake of [3H]dopamine, an index for the density of nigrostriatal dopaminergic terminals, and the maximum number of membrane [3H]tyramine binding sites, reflecting the concentration of the vesicular transporter for dopamine, were decreased in the hypothyroid striatum. There was also a loss of those D1-type dopaminergic receptors claimed to be located on neurons intrinsic to the striatum, and, consequently, dopamine-stimulated, D1-regulated adenylate cyclase activity was depressed. It is suggested that individual dopaminergic nerve endings in the neonatal hypothyroid striatum must contain more dopamine, owing to some loss of pertinent innervation and, therefore, to the presence of less vesicular transport sites for dopamine. Hypothyroidism-related decreases in the maximum number of striatal D1- and, reportedly, D2-receptors, plus the impairment of D1-coupled second messenger activity, may play a role in the derangement of those neurobehavioural patterns where a dopaminergic regulation is putatively implied. PMID- 2199847 TI - Double-blind, placebo-controlled trial of botulinum toxin injections for the treatment of spasmodic torticollis. AB - We enrolled 55 patients in a double-blind, placebo-controlled, parallel design study of the effectiveness of botulinum toxin (Botox) injections for the treatment of spasmodic torticollis. Patients received a standard series of injections, either placebo or Botox. We determined the sites of injection and dose per muscle by the nature of head deviation. Compared with placebo, Botox produced statistically significant improvement in the severity of torticollis, disability, pain, and degree of head turning. There were no serious side effects. During the double-blind phase, 61% of patients injected with Botox improved; 74% of patients subsequently improved during a later open phase at a higher dose of Botox. Direction of head turning, severity of torticollis, and presence or absence of jerky movements did not significantly influence the response rate. We conclude that Botox is a valuable treatment for spasmodic torticollis. PMID- 2199848 TI - The occurrence of oligoclonal IgG in tears from patients with MS and systemic immune disorders. AB - Using isoelectric focusing (IEF) and immunoperoxidase staining of proteins transferred to nitrocellulose membranes, we have examined the IgG band pattern in tears and matched serum and CSF specimens of 28 patients with MS, 4 patients with optic neuritis (ON), 30 individuals with systemic, inflammatory, or other neurologic diseases, and 5 patients with tension headache. We found no evidence of positive oligoclonal IgG in tears in any MS or ON patients, while 10 out of 16 cases with systemic immune disorders or infections of the CNS had positive tear oligoclonal bands. We are thus not able to support the hypothesis that tears from MS patients reveal abnormalities in their humoral immune response. PMID- 2199849 TI - Partial dystrophin deficiency in monozygous twin carriers of the Duchenne gene discordant for clinical myopathy. AB - We studied monozygous twin women, age 63. One, asymptomatic, had a serum creatine kinase (CK) level of 191 units (normal, 1 to 50); her son died of typical Duchenne muscular dystrophy (DMD) at age 18. Her twin sister had symptomatic limb weakness from about age 40. Her serum CK was 495 units. EMG and muscle biopsy were compatible with myopathy. In the asymptomatic twin, the peripheral blood lymphocyte karyotype was 46,XX. In the affected twin, 18% of cells were 45,X, and the others 46,XX, without X/autosome translocation. DNA analysis did not reveal a deletion at the DMD locus. Immunologic studies of dystrophin showed a partial deficiency of the protein that was more severe in the symptomatic twin. The clinical discordance and the different severity of dystrophin deficiency may have resulted from the effects of lyonization. PMID- 2199850 TI - Spontaneous isolated innominate artery dissection. PMID- 2199851 TI - [Insulin resistance in patients with Graves' disease and reduced glucose tolerance. The normalization of fasting insulin secretion in parallel with the restoration of thyroid function]. AB - In order to investigate the nature of impaired glucose tolerance (IGT) in 3 young patients with Graves' disease we have studied their insulin secretion fasting and in response to oral glucose by means of measurement of serum C-peptide. Fasting levels of serum C-peptide of these patients were beyond the range of 15 age matched normal subjects; the C-peptide/glucose ratio was also significantly higher (p less than 0.001) in the patients than in the controls. Following glucose ingestion serum levels of C-peptide resulted high in the range of normals, with a mean C-peptide/glucose ratio greater than in the controls, but without reaching of statistical significance. To investigate whether the anomaly in fasting insulin secretion of these patients had any correlation with their hyperthyroidism, afterwards we surveyed fasting concentrations of serum C-peptide in parallel with progressive variations of serum free thyroxine and triiodothyronine (FT4 and FT3) and thyrotrophin (TSH) during antithyrotoxic treatment with methimazole. The data of 23 tests on serum FT3 and FT4 levels, carried out during 16-18 months, resulted in significant correlation with contemporaneous measurements of fasting serum C-peptide (p less than 0.001). No significant correlation was found between serum TSH and fasting C-peptide levels. The results suggest that IGT of the patients in this study is not dependent on lacking insulin secretion, but on mild insulin resistance. Such glucose metabolic anomaly appears to be in clear correlation with the degree of hyperthyroidism, even if its pathogenesis remains to be further investigated. PMID- 2199852 TI - [Detectable hypoechogenic images in diffuse hepatic steatosis: a new ultrasonic finding in the differential diagnosis of expansive lesions of the liver]. AB - The authors describe a particular ultrasound finding which can sometimes be observed in the echographic picture of diffused hepatic steatosis and which was seen by these Authors in 117 out of 312 patients affected by steatosis. This finding consists of the presence of one or more hypoechoic focal areas situated at the IV-V and/or II-III segment level surrounded by widespread increase in echogenicity of remaining parenchyma, which is typical of "bright liver". These areas, which can easily be mistaken for neoplastic formations, were instead seen to be limited areas of normal liver parenchyma free of fatty infiltration. In those patients presenting valid reasons for suspecting the presence of primary or secondary neoplastic formations, the Authors believe that echographic examination of these areas should always be accompanied by more invasive methods in order to confirm or exclude the possible presence of neoplastic formations with certainty. On the contrary, in those patients where no such diagnosis is suspected, it should prove sufficient to monitor these areas by means of ultrasounds. PMID- 2199853 TI - [A clinical study of cyclopyroxolamine versus clotrimazole in the treatment of mycotic vulvovaginitis]. AB - The therapeutic efficacy and tolerability of the antifungal agent ciclopiroxolamine have been verified with a double-blind study versus clotrimazole in 46 patients affected by vulvovaginal candidiasis. The patients of the first group (23) have been treated with ciclopiroxolamine globules, one 100 mg globule nightly for six days; the second group (23 patients) received clotrimazole vaginal tablets, one 200 mg tablet nightly for six days. Ciclopiroxolamine treatment showed an equivalent effectiveness to that of clotrimazole both on signs and symptoms and on vaginal smear culture. No local or systemic adverse reaction was observed. PMID- 2199854 TI - [Imported malaria. The description of a rare clinical case]. PMID- 2199855 TI - [LHRH-analogues: clinical results in ovarian and breast cancer]. AB - The paper reviews the studies published between 1982 and 1989 on the subject of the use of LHRH analogs in gynecological oncology. Following the analysis of hormonal changes induced by analogue therapy in premenopausal women with advanced stage breast cancer, the clinical results obtained through the clinical treatment of this neoplasia are reported. Results to date are encouraging and analogue therapy still represents an alternative to surgical sterilisation. The clinical findings in postmenopausal women are less encouraging. In both pre- and postmenopause groups, findings were correlated to the receptorial status and site of metastases. The possibility of associating analogues to other hormone replacement therapies, or to chemotherapy is then discussed. Lastly, preliminary data concerning the use of analogue therapy in advanced-stage ovary cancer are analysed. The current indications for therapy and problems still to be resolved concerning the use of LHRH analogue therapy in the context of gynecological oncology are summarised by way of conclusion. PMID- 2199856 TI - [Ultrasonic study of the predictability of fetal macrosomia]. AB - Main fetal echobiometric parameters have been considered in 643 pregnant patients and evaluated for fetal macrosomia predictivity. Deliveries occurs within seven days after ultrasound examination. Malformative or other pathologic conditions with could have interfered with a correct ultrasound evaluation of the disease have been excluded. The single parameters are not reliable for a screening of fetal macrosomia. The A. suggest, for a greater accuracy, sequential ultrasound examination during pregnancy or mathematical correlation of several echobiometric parameters. PMID- 2199857 TI - [Beta 2-microglobulinuria and lysozyme-uria. Their role as diagnostic and therapeutic indicators in dilatation of the upper urinary tract during pregnancy]. AB - In a prospective clinical trial the diagnostic and therapeutic validity of beta 2 microglobulinuria (as an indicator of tubulointerstitial damage) and lyzozymuria (as an indicator of granulomonocytic activity in urinary tract) was studied in pregnant women with dilatation of the upper urinary tract and its possible complications (urinary tract infections, acute pyelonephritic episodes). A pathologically increased beta 2-microglobulinuria (greater than 300 micrograms/l) was found in all of the infectious episodes of upper urinary tract: pyelonephritis (PN) with concomitant tubulointerstitial lesions. Asymptomatic PN episodes could also be recognized by increased beta 2-microglobulinuria. A normal beta 2-microglobulinuria (less than 300 g/l) in pregnant women can--inspite of dilatation of the pyelon--be considered as primary or secondary (after chemotherapy) absence of infection of the upper urinary tract. Furthermore, any functional damage of the tubulointerstitial tissue, possibly caused by the pyelondilatation during pregnancy, can be excluded. A positive lysozymuria (less than 0.3 mg/dl) indicates the infection of the lower and/or upper urinary tract; also asymptomatic infectious episodes may be detected. A negative lysozymuria (less than 0.3 mg/dl) proves the absence of any infection in the lower and upper urinary tract. Pseudo-infections, caused by contamination, can also be revealed. The determination of beta 2-microglobulinuria and lysozymuria increases the diagnostic and therapeutic potency in the evaluation of dilatation of upper urinary tract and its complications during pregnancy. PMID- 2199858 TI - [Vulvar dystrophy]. AB - The pathogenetic, diagnostic and therapeutic aspects of vulvar dystrophies are reviewed, special attention being paid to a comparison of therapeutic tendencies past and present. The advantages of topical treatment with corticosteroids and testosterone and those of the most recent surgical techniques are compared respectively with the results obtained in past years using estrogenic topical treatment and demolition surgery. PMID- 2199859 TI - [A Sicilian multicenter study of the clinical effectiveness and tolerability of nimesulide in gynecologic inflammatory diseases]. AB - Hundred-eighty patients, aged between 18 and 58 years, participated in a multicenter study, in order to assay the efficacy and tolerability of nimesulide in gynaecological inflammatory diseases. Thirty patients were affected by adnexitis, 41 patients by cervicitis, 6 by endometritis, 13 by myometritis and 90 patients presented more pathologies associated. Al the patients were treated with nimesulide 100 mg granular (sachets) bid for a mean period of 19 days. Treatment with nimesulide produced good results in all pathologies, significantly reducing the intensity of symptomatology. The tolerability of the drug was always good. PMID- 2199860 TI - [A rare case of echinococcal cyst located in the ovary]. AB - A rare case of echinococcosis ovarian cyst is reported. The diagnostic difficulties this pathology may present, are underlined. PMID- 2199861 TI - Is guidance of chick retinal axons in vitro influenced by proteases? AB - Rhodamine-labeled explants of embryonic chick retinae were placed on a substratum consisting of alternating lanes of cell membranes derived from anterior and posterior chick optic tectum. Extending axons from temporal retinae prefer to grow in vitro on anterior tectal membranes because of a repulsive component within posterior membranes obtained from a tectum area which is not innervated by these axons in vivo. None of 16 protease inhibitors, specific for all known protease classes, when added to the culture medium, neutralized the repulsive activity of posterior membranes suggesting that the repulsive activity is not a protease. However, 2 metalloprotease inhibitors affect growth cone morphology and axon-axon interactions. PMID- 2199862 TI - Neuronal alterations in patients with dementia: a Golgi study on biopsy samples. AB - Golgi-impregnated neurons in biopsy samples of the cerebral cortex (area 8) of patients with Alzheimer's disease (AD), Pick's disease (PD) and Creutzfeldt-Jakob disease (CJD), but not in control samples, have swellings in the proximal and mid regions of dendrites of pyramidal and non-pyramidal cells that differ from normal dendritic varicosities. Dendritic outgrowths, isolated or in clusters, and covered with spines occur only in neurons with reduced dendritic arbors mainly located in the vicinity of senile plaques. Degenerating pyramidal and non pyramidal neurons, although distributed throughout the cerebral cortex in CJD and PD, predominate in layers II, III and VIb in patients with AD. PMID- 2199863 TI - Will new fee system slash physician payments. PMID- 2199864 TI - A comparison of the ability of a sonographically measured biparietal diameter and the last menstrual period to predict the spontaneous onset of labor. AB - To study whether the estimated date of confinement (EDC) for women with optimal menstrual histories is predicted best from the last menstrual period (LMP) or biparietal diameter (BPD), 2320 women had the EDC estimated by both LMP and BPD measured sonographically in the second trimester. Those who delivered after the spontaneous onset of labor are reported here. Compared with the EDC calculated from the LMP, the EDC calculated from the BPD was postponed more than 1 week for 406 women (17.5%) and advanced more than 1 week for 56 (2.4%). For these women, the BPD estimate of EDC turned out to be closer to the day of delivery in 264 cases, whereas the LMP estimate was closer in 125 (P less than .001). For 73 women, the estimates were equally good. For 80.1% of the women, the two estimates of EDC differed by 1 week or less; in these cases, the estimates were equally good in predicting the day of delivery. We conclude that the BPD is a better predictor of the spontaneous onset of labor than is the LMP. PMID- 2199865 TI - Maternal obesity: a potential source of error in sonographic prenatal diagnosis. AB - Sonograms from 1622 consecutively scanned singleton pregnancies at a mean gestational age of 28.5 weeks were analyzed to determine whether maternal obesity affected visualization of fetal anatomy. Fetal head (cerebral ventricles), heart (four-chamber view), stomach, kidneys, bladder, diaphragm, intestines, spinal column, extremities, and umbilical cord were classified as visualized or suboptimally visualized. Maternal body mass index was used as a measure of relative leanness. No significant impairment of ultrasound visualization was noted until a body mass index above the 90th percentile, when visualization fell by an average of 14.5%. Reduction in visualization was most marked for the fetal heart, umbilical cord, and spine. Among non-obese women, advancing gestation and decreasing body mass index were the most important determinants of visualization. However, among obese women, body mass index was the best predictor of visualization, with no improvement seen with advancing gestation or duration of examination. PMID- 2199866 TI - Antibiotic prophylaxis for cesarean delivery: is an extended-spectrum agent necessary? AB - The purpose of this investigation was to determine whether an extended-spectrum antibiotic with a long duration of action was more effective for prophylaxis for cesarean delivery than a limited-spectrum agent with a shorter duration of action. Patients were eligible for the study if they were in labor or had ruptured membranes at the time of surgery. In a randomized, double-blind manner, 377 women were assigned to receive 2 g of cefazolin (192) or 2 g of cefotetan (185) intravenously immediately after the infant's umbilical cord was clamped. There were no significant differences between groups with respect to the frequency of febrile morbidity (22.4 versus 21.6%), the mean fever index (15.8 versus 14.9 degree-hours), the frequency of endometritis (19.3 versus 21.1%), or the mean duration of postoperative hospitalization (3.8 versus 3.9 days). Among patients who became infected despite prophylaxis, enterococcus was isolated with disproportionate frequency. This organism was responsible for 89% of the postoperative urinary tract infections and all three cases of bacteremia. It was also the second most common isolate in women with endometritis. A single dose of cefazolin is comparable in effectiveness to cefotetan. In view of the cost difference between the two antibiotics, there is no justification for use of the more expensive, extended-spectrum agent. PMID- 2199867 TI - Variability of continuous-wave Doppler flow velocity waveform indices from the umbilical artery. AB - Using continuous-wave Doppler ultrasound, the reproducibility of umbilical artery blood flow velocity waveforms, recorded by two operators, was evaluated in 20 high-risk antenatal inpatients. Inter-operator variability was not significant for any index. The intra-operator coefficients of variation for resistance index, pulsatility index, and systolic/diastolic ratio were 7 and 7%, 12 and 12%, and 15 and 11%, respectively, for each operator. The intra-class coefficient of reliability, calculated by analysis of variance, indicated that the contribution of inter-patient variability to total variance was four times that of intra operator variability. PMID- 2199868 TI - Sonographic growth measurements in triplet pregnancies. PMID- 2199869 TI - Maternal group B streptococcal vertebral osteomyelitis: an unusual complication of vaginal delivery. AB - A 42-year-old woman developed severe neck pain 20 hours postpartum. She had cervical spondylitis from an accident 15 years earlier. An elevated sedimentation rate was the only abnormal laboratory finding. Vertebral osteomyelitis was diagnosed by magnetic resonance imaging 12 days postpartum. She underwent radical debridement of C5 and C6 with anterior fusion because of neurologic deterioration and extensive vertebral destruction. A posterior fusion was performed 7 days later for additional stabilization. Group B streptococci were cultured from the debridement tissue. The patient received 8 weeks of intravenous antibiotics. Residual disability at 3 months involved minimal dysesthesia of all extremities. PMID- 2199870 TI - Prenatal diagnosis of chondrodysplasia punctata by sonography. AB - The rhizomelic form of chondrodysplasia punctata is a lethal autosomal recessive disorder of unknown cause. It is characterized by marked shortening and bowing of the proximal limbs, vertebral column abnormalities, eye and skin defects, severe mental retardation, and recurrent infection. Previously, antenatal diagnosis of this condition was made by radiography. We describe ultrasonographic findings, specifically stippling of the proximal humerus, which permitted us to identify the condition in a fetus at 28 weeks' gestation. PMID- 2199871 TI - Intraluminal bladder calcifications: an antenatal sign of an enterovesical fistula. AB - Anorectal agenesis is usually associated with a fistula to the bladder, urethra, or vagina. The sonographic detection of a meconium concretion in the fetal bladder strongly suggests the presence of an enterovesical fistula. PMID- 2199872 TI - Diagnosis of vasa previa with transvaginal and color flow Doppler ultrasound. AB - Vasa previa, which is associated with high fetal mortality, is present when fetal vessels cross the internal cervical os as a velamentous insertion of the umbilical cord with or without a succenturiate lobe or bilobate placenta. This is the first case report of vasa previa not associated with a succenturiate lobe or bilobate placenta and in which the diagnosis was made using a combination of transvaginal ultrasonography and color flow Doppler ultrasound. The infant was delivered by elective cesarean, and the ultrasound findings were confirmed. Color flow Doppler and transvaginal ultrasound facilitate this diagnosis because the internal os and surrounding structures are easier to visualize; in addition, vascular flow and Doppler patterns characteristic of the umbilical cord can be demonstrated in structures suspected to be vessels. PMID- 2199873 TI - Maternal lithium therapy and polyhydramnios. AB - Lithium is widely used in the treatment of bipolar affective disorders, and teratogenic effects include cardiovascular abnormalities, notably Ebstein anomaly. The most common side effect in the patient taking lithium is polyuria, a form of nephrogenic diabetes insipidus. We report the case of a manic-depressive gravida on lithium therapy who developed polyhydramnios in her last trimester. Because lithium crosses the placenta, we postulate that, by a similar mechanism, lithium may cause fetal polyuria which results in polyhydramnios. PMID- 2199874 TI - Primary adenocarcinoma of the breast arising in the vulva. AB - Primary adenocarcinoma of ectopic breast tissue in the vulva has been reported in only four instances. A fifth case, in which estrogen and progesterone receptors were present, is described. Estrogen and progesterone receptor studies may be helpful in identifying adenocarcinoma of uncertain origin. PMID- 2199876 TI - Vasectomy: an appraisal for the obstetrician-gynecologist. AB - Data regarding the efficacy of vasectomy are limited, but the procedure appears to be highly effective. Efficacy may vary by the method of vas occlusion. Death attributable to vasectomy in the United States is exceedingly rare, and major perioperative morbidity is quite uncommon. No long-term adverse health effects have been documented, and much evidence supports the conclusion that vasectomy does not increase the risk of subsequent atherosclerosis. Vasectomy, like tubal sterilization, should be considered a permanent decision, because reversal surgery is expensive and requires substantial surgical expertise. Although vasectomy reversal is often successful, it cannot be guaranteed even in the best of circumstances, and when the vasectomy has caused epididymal obstruction, reversal is often unsuccessful. Vasectomy represents a safe and effective alternative to tubal sterilization for couples who decide that the male should be sterilized. PMID- 2199875 TI - A guide to interpreting contraceptive efficacy studies. AB - Results of trials of various birth control methods and contraceptive products may provide misleading data and engender unrealistic expectations regarding efficacy. An analysis of published efficacy-trials reveals numerous fallacies in their design, performance, and reporting. Consequently, family planning clinicians find it virtually impossible to make valid comparisons among the methods or products. This article reviews the definitions and measures that have been used to assess contraceptive efficacy, describes and illustrates some of the flaws that confound interpretation and comparison of studies, and presents a set of recommendations for future studies. A summary table providing comparative failure rates for all methods of contraception is included. PMID- 2199877 TI - Anterior stromal puncture for recurrent erosion: further experience and new instrumentation. AB - Anterior stromal puncture has recently been proposed as a new treatment for recalcitrant cases of recurrent corneal erosion. Concerns about the risks of corneal perforation and scarring, as well as doubts regarding its efficacy have prevented many patients from benefiting from this procedure. We introduce a new, inexpensive, commercially available instrument designed to standardize this technique, minimize scarring, and prevent corneal perforation. In a clinical trial involving 25 consecutive patients with recurrent erosions resistant to vigorous conservative treatment, the first 11 patients underwent stromal puncture in which a straight tuberculin needle was used; the following 14 were treated with a newly designed prototype needle. All patients in this series remained free of erosions after completion of stromal puncture, except for one woman with marked diffuse anterior basement membrane dystrophy, who went on to develop spontaneous bilateral erosions. Follow-up ranged from 2 months to 30 months (mean, 13 months). There were no complications of stromal puncture, and subjective and objective evaluations revealed no significant postoperative glare. Microscopic analysis of eye bank eyes subjected to anterior stromal puncture procedures demonstrated that the new prototype needle provided shallower penetration and thus less likelihood of perforation or excessive scarring than the straight needle. Also, postoperative discomfort and scarring appeared to be significantly less in patients treated with the prototype needle. PMID- 2199878 TI - The effect of relaxing incisions with multiple compression sutures on post keratoplasty astigmatism. AB - We describe a surgical technique for correction of astigmatism following penetrating keratoplasty performed after all keratoplasty sutures have been removed. Two relaxing incisions of 3 clock hours, at 3/4 depth, 0.5 mm inside the keratoplasty wound are used in combination with two sets of three compression sutures placed 90 degrees from the incisions. Selective removal of the compression sutures allows for a graded reduction in overcorrection. With this technique, a mean preoperative astigmatism in 10 patients of 14.25 diopters was reduced to 6.33 D 3 months postoperatively (P less than .002). There were no intraoperative or postoperative complications such as inadvertent perforation, wound dehiscence, or graft rejection. PMID- 2199879 TI - Lacrimal tube repositioning: technique and ultrasonic assessment. AB - A section of migrated lacrimal silicone tubing was repositioned in a 7-year-old patient by dilating the lacrimal passage with hyaluronate solution and pushing the tube back into the nasal fossa with a probe. The position of the tube was postoperatively confirmed by ultrasonographic studies. PMID- 2199880 TI - Surgical management of congenital upper-eyelid eversion. AB - We describe a case of congenital eversion of the upper eyelids in which early surgery was performed to prevent occlusion amblyopia. The surgery, described here for the first time for this condition, consisted of using multiple suture placements to anatomically reposition the eyelids. PMID- 2199881 TI - Single stage Molteno implant with combination internal occlusion and external ligature. AB - A variety of techniques have been devised to reduce postoperative hypotony following a single-stage Molteno implant procedure. Although they effectively reduce hypotony, these techniques may result in a prolonged increase of intraocular pressure (IOP). I present a technique, consisting of placement of a 5 0 nylon internal occlusion suture combined with an external polyglactin (Vicryl) ligature around the Molteno tube, to prevent both hypotony and elevated IOP after implantation. PMID- 2199882 TI - The Charles Prentice award lecture 1989: the physiology of tears. PMID- 2199883 TI - Sunlight as an ultraviolet source. AB - An understanding of the spectral composition of sunlight is necessary if the effects of human exposure and protection criteria are to be meaningful. Also provided is a brief review of data for the ultraviolet UV solar spectrum in space and on earth that have been related to ocular damage. In addition, the effects of increases and decreases in the levels of ozone on the amount of ultraviolet radiation (UVR) reaching earth are presented. It is shown that enough UVR is encountered on earth to cause ocular damage and the damage will increase significantly as the levels of ozone decrease. PMID- 2199884 TI - The Sunglass Standard and its rationale. AB - This paper reports on the 17-year development of the current Z80.3 Sunglass Standard. The dioptric tolerances of +0.125 to -0.25 D power, 0.125 D astigmatism, 0.25 delta prism, and 0.18 D power imbalance are based on research by optometry's leaders. The traffic signal and luminous transmittance requirements are the result of study of the literature and original research. There has been much misunderstanding regarding the UV transmittance specifications. They too were exhaustively researched and discussed. That work is reviewed in detail. New equations for calculating exposures are presented with sample spectra. Graphic evaluations of severe risk exposures are presented. They show that based on the accepted criteria, for reasonable assumptions the Standard offers a 10x margin of safety. Studies of retinal risk indicate the Standard provides ample protection. Some criteria need further study. Potential problems are based on the fact that some sunglasses are too dark for driving and that use of ordinary sunglasses for sports provides inadequate protection from injuries. PMID- 2199885 TI - Ultraviolet-absorbing spectacle lenses, contact lenses, and intraocular lenses. AB - Optical materials that are available to the practitioner for protection of the eye against hazardous exposure to ultraviolet radiation (UVR) are discussed. Principles of protection, procedures for calculating safe ocular exposure duration, and transmittance curves of commonly prescribed spectacle lenses, contact lenses, and intraocular lenses are discussed. Suggestions are made to assist the practitioner in providing adequate protection for the patient. PMID- 2199886 TI - Levator aponeurosis surgery. PMID- 2199887 TI - Nonocular cancers in patients with choroidal melanoma. PMID- 2199888 TI - The "learning effect" in automated perimetry. PMID- 2199889 TI - Bilateral ischemic optic neuropathy and retinal vascular occlusions associated with lymphoma and sepsis. Clinicopathologic correlation. AB - The authors report the clinicopathologic correlation of a patient with non Hodgkin's mixed-cell lymphoma who had impairment of the circulation of the optic nerve and retina in both eyes. The results of histopathologic examination showed that the pial septa of the optic nerves were infiltrated by lymphoma and that there was extensive infarction of the orbital portions of both optic nerves and occlusion of both central retinal arteries and the right central retinal vein by thrombi with bacteria. The infiltration of the optic nerves seemed to be resistant to therapy. PMID- 2199890 TI - An adjustable single running suture technique to reduce postkeratoplasty astigmatism. A preliminary report. AB - The authors compared postkeratoplasty astigmatism over a 4-month period after surgery in a randomized, prospective study of two groups of patients (total N = 18) who received two different suture techniques. The test group N = 8) had a single running suture with postoperative suture adjustment; on the basis of computer-assisted topographic analysis, the suture was tightened in the flatter meridian and loosened in the steeper meridian in the first month after surgery. The control group (N = 10) had a standard double running suture procedure with no postoperative adjustment; the single running 10-0 nylon suture was removed 3 months after surgery. Four months after penetrating keratoplasty, mean (+/- standard deviation) astigmatism in the test group was 1.7 +/- 0.7 diopters (D), and all patients had less than 2.6 D of astigmatism. In the control group, mean astigmatism was significantly higher (5.4 +/- 2.4 D; range, 0.7-9.0 D; P less than 0.01). The results suggest that postkeratoplasty astigmatism can be reduced with the single running suture technique accompanied by postoperative suture adjustment. PMID- 2199891 TI - Cicatricial pemphigoid and erythema multiforme. AB - Cicatricial pemphigoid (CP) and erythema multiforme (EM) are bullous diseases that involve the skin and mucous membranes including the conjunctiva. Of all the bullous diseases, CP and EM not only involve the conjunctiva most frequently but also cause the most severe conjunctival disease. A chronic, progressive disease, CP is characterized by shrinkage of the conjunctiva, symblepharon, entropion, trichiasis, dry eye, and finally reduced vision from corneal opacification. It is primarily a disease of the elderly that affects more women than men and is characterized by blisters or bullae in a subepithelial location and immunoglobulins and complement bound to the basement membrane zone of skin and mucous membranes including the conjunctiva. Circulating antibodies to the basement membrane zone can be demonstrated occasionally. Treatment includes artificial tears, topical antibiotics, correction of entropion and trichiasis, therapeutic soft contact lenses, and systemic immunosuppressive therapy including corticosteroids. An acute, generally self-limited, inflammatory disorder of the skin and mucous membranes, EM occurs primarily in young, healthy individuals. The most frequent precipitating factors are (1) drugs and (2) infections caused by Mycoplasma pneumoniae and herpes simplex. Conjunctival involvement ranges from a mild catarrhal conjunctivitis which terminates without sequelae to membranous conjunctivitis which may heal leaving scarring, symblepharon, and even ankyloblepharon. Histopathologic findings include subepithelial bullae and perivascular mononuclear cell infiltrates. Patients with EM have circulating immune complexes and immunoreactant deposition in the blood vessel walls of the dermis. After the acute episode has subsided, they may require artificial tears, topical antibiotics, correction of entropion and trichiasis, therapeutic soft contact lenses, tarsorrhaphy, and mucous membrane grafts. PMID- 2199892 TI - [Factors influencing leukemic transformation in myelodysplastic syndrome]. AB - Prognostic factors affecting the leukemic transformation were studied in 43 patients with myelodysplastic syndrome (MDS). Acute leukemia developed in 17 cases and it was nonlymphocytic leukemia in every case. No remission was achieved following antileukemic therapy and most of the cases proved to be true drug resistant leukemia. Initial granulopenia, thrombopenia or anemia alone did not influence the occurrence of leukemic transformation but pancytopenia indicates bad prognosis. According to FAB classification especially refractory anemia with excess of blasts (RAEB) and RAEB in transformation (RAEB-T) were often followed by leukemic transformation. The granulocyte-macrophage progenitor cell (GM-CFC) content of bone marrow were also studied. The GM-CFC content was decreased in each patient. There was no correlation between GM-CFC number and leukemic transformation, the growth-pattern in agar-gel culture, however, turned out to have prognostic importance. Leukemic type of growth, namely always preceded leukemic transformation. PMID- 2199893 TI - [Adaptation of the esophagus, reconstructed using the colon, based on 135 cases of surgery in corrosive stenosis]. AB - Late aspects of adaptation were studied on the basis of 135 esophagoplasty by means of isoperistaltic (except of 7 anisoperistaltic) transverse colon for corrosive strictures. Histochemically, the augmentation of neutral mucopolysaccharide, which increases mucosal resistance--was observed on the surface and in Lieberkuhn glands of colonic mucosa. Mucosal absorption remains unmodified. Transit time is considerable longer, but without functional consequences. Radiokinematographically, characteristic, coordinated, multihaustral, propulsive movements of transverse colon were present, playing a secondary, but active role in the swallowing mechanism. In the authors opinion, the marked differences between the iso- and anisoperistaltic interposition modality, in point of view of gastro-colic reflux, is explained by these unmodified, more independent, motor activity of the bowel wall. Good long-term functional results were present in 92% of patients. In management of corrosive strictures, isoperistaltic transverse colon may be considered the graft of choice, both technically and functionally. PMID- 2199894 TI - Sleep apnea--an historical perspective. AB - In this article the authors have attempted to give the reader a brief overview of some of the development of recognition of obstructive sleep disorders and early aspects of their surgical therapy. They have avoided detailed descriptions of radiographic and other diagnostic measures, since many of these are summarized in other articles. PMID- 2199895 TI - Polysomnography methods and interpretations. AB - As the field of sleep disorders medicine continues to mature, appropriate diagnostic techniques are becoming properly defined and standardized. This article focuses principally upon diagnostic testing for sleep apnea, although other sleep disorders are discussed briefly. When interpreting a polysomnogram, one must consider a number of complex variables. A critical discussion of the methods for adequately measuring these variables is provided together with guidelines for appropriate interpretation. PMID- 2199896 TI - Obstructive sleep apnea syndrome: a complex disorder of the upper airway. AB - The pathophysiologic basis for obstructive sleep apnea syndrome (OSAS) is complex, involving the properties of the pharynx, the muscular forces that support its patency, and the homeostatic control mechanisms of respiration. The anatomic basis for OSAS is the skeletal structure of the head and neck as it is reflected in the soft tissue structures comprising and supporting the upper airway. Study of patients with craniofacial anomalies that result in OSAS, and application of similar study techniques to OSAS patients without apparent craniofacial anomalies, point up similarities and lead to a greater understanding of the anatomic aspects of OSAS. PMID- 2199897 TI - Radiographic imaging of airway obstruction in pediatrics. AB - The authors review techniques available to image the airway, normal radiographic airway anatomy, pitfalls in imaging the airway, and radiographic findings in various pathologic processes that may cause airway obstruction. A brief discussion of the application of imaging in the child with sleep apnea is included. PMID- 2199898 TI - Sleep disorders and airway obstruction in newborns and infants. AB - For most infants with a disorder of breathing control or airway obstruction, cause and management can be defined with a careful history and a few simple diagnostic tests. Pneumograms and multichannel studies can identify patterns of apnea and associated hypoxemia and can be used to assess therapeutic efficacy. For the majority of infants with disordered breathing, the outcome is favorable and conservative management is appropriate. More extensive diagnostic evaluation is reserved for infants with severe apnea or those with evidence of a significant contributing underlying disease. For these infants, management should be directed at the underlying cause and at identifying and preventing severe, life threatening events. PMID- 2199899 TI - Sleep disorders and airway obstruction in children. AB - Obstructive sleep disorders in children are not rare. Many parents will provide sufficient history to establish the diagnosis. Although there may be many causes of obstructive disorders, the most common in children is adenotonsillar hyperplasia. Aggressive treatment will result in prompt resolution of symptoms. PMID- 2199900 TI - Complications of pediatric obstructive sleep apnea. AB - Obstructive apnea, especially OSA, is a common problem in pediatric practice. In young infants, craniofacial anomalies may be the most common contributor to OSA. Complications include failure to thrive, metabolic alkalosis, and respiratory distress which can be life-threatening. In children over the age of 2 years, adenoidal and tonsillar hypertrophy is more commonly the cause of upper airway obstruction. The complications of growth failure, cor pulmonale, and adult respiratory distress syndrome were discussed. Obstructive sleep apnea can cause significant complications in both infants and children. These problems can be life-threatening, cause delay in growth and development, or cause subtle long term learning disabilities. Surgical management of the airway should correct the metabolic and cardiorespiratory disorders. The correction of learning disabilities has not yet been demonstrated. PMID- 2199902 TI - Effect of airway obstruction upon facial growth. AB - This article explores both sides of the controversy concerning respiratory behaviors and dentofacial development. The literature is replete with statements that airway impairment alters facial and dental growth, but there also is substantial evidence to the contrary. Much of the confusion stems from the subjective criteria frequently used in defining the terms impairment and mouth breathing. Additionally, respiratory mechanics have often been viewed simplistically rather than in the realistic sense of a complex regulation/control system. Unfortunately, lack of objectivity may lead to an incorrect diagnosis and even worse, inappropriate treatment. Newer respirometric techniques offering more quantitative assessment of respiratory behaviors are now providing more relevant information and more objective definitions of airway impairment and mouth breathing. More recent findings suggest that nasal-oral breathing per se is not necessarily harmful to growth. However, in instances when the nasopharyngeal or oropharyngeal airspace is small, exaggerated postural responses in obligatory nasal-oral breathers may be detrimental to growth. PMID- 2199901 TI - The tongue and airway. AB - Patency of the upper airway during sleep depends on a balance of forces. This article summarizes recent research undertaken by the author in the areas of tongue, soft palate and airway volume, tongue and pharyngeal edema, genioglossus muscle activity, and mandibular repositioning appliances. Three-dimensional relationships between airway, soft palate, and tongue can be quantified with accuracy, and such analyses may be of significant diagnostic importance. PMID- 2199903 TI - Home monitoring in infants and children with obstructive apnea. AB - It becomes apparent that the decision to prescribe home monitoring for the child who has, or is thought to be at risk for, obstructive apnea is not a straightforward one. There have been no studies documenting the effectiveness of home monitoring in this population. The risk of obstructive apnea in some children clearly supports the use of an obstructive apnea detection system. Unfortunately, the current home monitors are not designed to detect obstructive apnea. These monitors may alert parents to obstructive apnea by identifying the changes in heart rate that can accompany these episodes, but this warning may not be timely. There are a number of potential costs that may accrue to families who monitor their children. In some instances the "costs" of home monitoring may lead to failure of parents to comply with the treatment or to neglect of other aspects of their child's treatment regimen, thereby effectively increasing the child's risk of obstructive apnea. To achieve the maximum benefits of home monitoring requires high levels of commitment on the part of both the child's physician and his family. Parents need thorough preparation and continuous logistic and professional support if they are to carry out this monitoring. The physician should not need to provide all of this support, but he or she should expect to function in a co-ordinating capacity on behalf of the child and family. PMID- 2199904 TI - Sleep disorders and upper airway obstruction in adults. AB - The OSA syndrome, described over 100 years ago, was rediscovered in 1966. It is a common disorder, especially among fat, middle-aged men. Stentorian snoring and diurnal somnolence are the cardinal manifestations and should always lead to an examination during sleep. That examination (polysomnography) can demonstrate the pathognomonic events--repetitive apneas occurring in sleep--which signal the failure of the sleeping brain to maintain the patency of the supraglottic airway. All evidence points to the problem being an abnormal pharyngeal airway, one which has a shape or size or compliance that allows inspiratory collapse as the normal loss of pharyngeal dilator muscle tone occurs with sleep. The apneas are asphyxic events terminated by arousals which fragment sleep continuity and lead to the daytime sleepiness. Because the snoring occurs during sleep, the arousals are unremembered, and the sleepiness can develop so gradually that the patient may forget what normal alertness is like. It is important to interview the patient's spouse or partner. Besides obesity and maleness, other risk factors for OSA are diseases that have an impact on the configuration or effective compliance of the pharyngeal passageway. Recent studies support the clinical intuition that sleep apnea is undesirable. Sleepiness leads to accidents. The hypoxemia occurring during apnea can lead to potentially fatal cardiac dysrhythmias. A number of reports suggest that snoring and sleep apnea are associated with an increased risk of stroke, myocardial ischemia, and infarction. Finally, there are now two papers showing a significantly decreased probability of 5-year survival in patients with symptomatic sleep apnea. The good news is that treatment with tracheostomy or NCPAP improves mortality rates to normal. Approximately 90 per cent of patients can tolerate a night's initial trial with CPAP. Long-term acceptance of CPAP has now been reviewed in a number of studies, and it appears to be about 65 to 70 per cent. PMID- 2199905 TI - Monitoring adult patients with sleep apnea. AB - It can be said that there are two methods of evaluating certain aspects of sleep. PSM is more traditional and uses older equipment to assess a full scope of sleep disorders in a rather expensive and inconvenient way. Computerized home monitoring is a more modern way of monitoring sleep using improving technology, probably most applicable to snoring with sleep apnea, in a less expensive way. A joint study group should co-ordinate and encourage progress in both traditional and computerized procedures to the greater good of all. PMID- 2199906 TI - Obstructive sleep apnea and obesity. AB - OSA affects approximately 1 per cent of the adult male population and is more common among obese patients. The mechanism for the relationship between obesity and OSA may be mechanical obstruction or hypoxemia. Patients with obesity often have other medical problems that can exacerbate or complicate OSA. The physician should look for other problems such as diabetes, hypertension, and coronary disease while evaluating an obese patient with OSA. Weight loss is important either as a primary therapy or in conjunction with surgical treatment of OSA. Weight loss methods include behavior modification with diet, very low calorie diets with behavior modification, and bariatric surgery. In morbidly obese patients, more dramatic means such as bariatric surgery or very low calorie diets seem to be preferable because of the significant reduction in the length of time it takes for patients to lose weight. Because of a tendency for obese patients to regain weight, it is important to follow the patients long term to prevent the regaining of weight. PMID- 2199907 TI - Neurologic aspects of sleep apnea and related respiratory disturbances. AB - Several types of neurologic diseases can contribute to disturbed respiration during sleep. Abnormal function of respiratory and upper airway muscles can occur with neuromuscular diseases and lead to upper airway obstruction and alveolar hypoventilation during sleep. Central nervous system disorders that cause dysarthria and dysphagia can also lead to obstructive and central sleep apnea, even in the absence of the usual anatomic deformities associated with OSA. Appropriate treatment requires an understanding of the effect of the underlying disease process on upper airway and respiratory function. PMID- 2199908 TI - Evaluating the patient with a difficult airway for anesthesia. AB - Patients with difficult airways present a challenge when they must undergo anesthesia. This article examines the problems inherent in evaluating patients with difficult airways for surgery. The authors believe that these patients are best evaluated in a Difficult Airway Clinic. The structure and organization of such clinics are examined. PMID- 2199910 TI - From inkblots to art therapy. PMID- 2199909 TI - Surgical management of obstructive sleep apnea. AB - The authors have reviewed the surgical management of patients with OSA. They have emphasized not only surgical techniques but also the method of preoperative evaluation of the patients and have presented some considerations in the postoperative management of patients in an attempt to avoid catastrophic results. As our diagnostic techniques improve, we should have fewer problems with the determination of the amount of tissue to remove and also the selection of the appropriate procedure. The advent of flexible laryngoscopy, cineradiography, and cine CT may indeed improve our diagnostic and therapeutic capabilities. PMID- 2199911 TI - Physician pioneer honored in Clearfield County. PMID- 2199912 TI - Society president writes on Medicare. PMID- 2199913 TI - [Correctable abnormalities]. PMID- 2199914 TI - [The heart in endotoxin shock]. PMID- 2199915 TI - Future role of the pediatrician in child abuse and neglect. AB - This article reviews the recent history of responses to child abuse and the present roles of pediatricians. It outlines actions that are needed to protect children, recognizes the difficulties in effecting intervention, and concludes that pediatricians cannot afford to stand by while children continue to suffer harm. PMID- 2199916 TI - Inflicted injury versus accidental injury. AB - The morbidity and mortality that are associated with child abuse is a serious concern for the practicing pediatrician. If abuse is to be prevented, physicians must become skilled in recognizing factors that place a child at risk for abuse. Early and minor signs of abuse and neglect must be recognized and reported to assure services if more serious abuse and neglect are to be prevented. Instruments that are used to strike children or burn them leave their imprint on the child. Marks on the skin may signal the existence of internal injuries. Nonaccidental injuries may be difficult to distinguish from accidental injuries. Physicians must approach an injury as a symptom requiring a diagnosis of cause. This is best accomplished by careful examination and documentation of each injury. If the injury is not in keeping with the history given or the child's level of development, abuse must be considered as a cause. A suspicion of abuse should result in a report. PMID- 2199917 TI - Radiologic imaging of inflicted injury in the child abuse syndrome. AB - Injuries associated with child abuse may involve any anatomic focus and organ system. Although many if not most of the injuries associated with physical abuse cannot serve as definitive evidence of maltreatment, awareness of patterns of injuries in abused infants and children initially may serve to identify potential victims of abuse and stimulate more thorough clinical and radiologic investigation. It is essential that less familiar intracranial and abdominal injuries be thoroughly evaluated for possible abuse when circumstances suggest maltreatment, or no plausible explanation is given for radiologic findings. PMID- 2199918 TI - The medical evaluation of the sexually abused child. AB - The diagnosis of suspected sexual abuse is nearly always based on a description of abuse provided by the child. The physician should invite a child to describe his or her sexual victimization in detail if such a "disclosure" interview has not already occurred, if the child seems ready to describe the abuse, and if a child protective services worker has not yet been notified of the suspected abuse. If an allegedly abused child has already been carefully interviewed, however, the physician should instead obtain information from the child's parents or other appropriate adults to determine how best to address the questions being raised. Nonspecific behavioral or somatic complaints unaccompanied by a specific description of sexual abuse should generate a differential diagnosis for further investigation. The goals of the physical examination of the sexually abused child are to identify abnormalities that warrant further diagnostic efforts or treatment, to obtain specimens to screen the patient for sexually transmitted infections, and to make observations and take specimens that may corroborate the patient's history of victimization. These goals should be met in the context of a standard, complete physical examination. The advisability of postcoital contraception should be discussed with every postmenarcheal victim seen within 72 hours after a rape. Because gonorrhea and chlamydial infections are the most prevalent STDs seen after sexual abuse and are often asymptomatic, universal screening for these infections is recommended. Parents of all abused children should be given an opportunity to make an informed choice about HIV screening. Because the risk of acquiring STDs is low, routine antibiotic prophylaxis is not recommended for sexually abused children. Physicians must report all cases of suspected sexual abuse to states' child protective services agencies. Failure to do so can incur legal penalties. Reporting sexual assaults of children to local law enforcement officials is strongly advised. The long-term impact of sexual abuse on children's psychological adjustment is unpredictable. In the short term, children's circumstances vary widely. Some show no evidence of psychological distress. Others have severe, pervasive difficulty. Office counseling by the empathetic and knowledgeable primary care physician, short-term crisis counseling, a more formal psychological evaluation, and longer-term psychotherapy may be recommended for individual children, depending on the nature and severity of each child's symptoms, his or her parents' preference, and the availability of services in the child's community. PMID- 2199919 TI - Use of the colposcope in childhood sexual abuse examinations. AB - The addition of the colposcope to the armamentarium of the medical investigator of childhood sexual abuse has many advantages. The ability to accurately record anatomic findings has implications for the medical community, the judicial system, the accused, the victim, and the family. Through the use of the photographs produced by this instrument, examiners can inspect physical findings without the time constraints imposed by the short attention span of the young child. If necessary, colleagues can be consulted and interpretations discussed. The availability of these photographs to the courts has reduced the need to re examine the child for another opinion. The colposcopic photograph has also proved to be an excellent teaching and research tool. As an aid to teaching, the photographs and slides produced by this instrument help the instructor demonstrate anatomic findings while allowing the student time to ask questions. As a research tool, this instrument has opened up a myriad of possibilities for medical examiners. It has facilitated the collection of clinical data, it has allowed the standardization of examination techniques, and with the help of computers it has made possible the sophisticated analysis of the information collected. The colposcope has limitations. Aside from its cost, it is a difficult instrument to use in the examination of the young child. The time required for an examination can increase substantially as the examiner attempts to maneuver the scope into a proper position. During this procedure, the maintenance of the child in a suitable state of relaxation, while avoiding further emotional trauma, can be a challenge. The reality that the photograph is two dimensional and represents only the findings at that moment will always be a limiting factor in its use as a means of assessing a child's anatomy. Even the multimethod approach employed to offset this problem may compound the situation by further increasing the length of the examination. Most of these and other dilemmas encountered in the use of the colposcope can be solved by additional experience with this instrument. Despite the improvements brought about by the introduction of the colposcope, more advanced technology may be needed to help solve some of the problems currently plaguing medical examiners. The use of video tape could provide a solution to the documentation of the changes that occur in the soft tissues as the child moves or becomes more or less relaxed. The potential of the computer appears unlimited, and its application to the problem of the interpretation of findings could make a significant contribution to the field.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2199920 TI - Substance abuse and child abuse. Impact of addiction on the child. AB - At least 1 in 10 children in the United States is born into a chemically dependent family. Parental addiction has long-lasting detrimental effects on the health and safety of children. We must mobilize to free children from the double jeopardy of substance abuse and child abuse, and interrupt the multigenerational pattern of both problems. The short-term costs may be high, but the long-term costs will be much higher if we do not act. Simultaneous efforts are needed to prevent and treat both addiction and its too frequent consequence, child maltreatment. PMID- 2199921 TI - Unusual manifestations of child abuse. AB - Cases of child abuse are seen each day in the clinics, emergency departments, private offices, and public and private hospitals. Unusual presentations are intermixed with the straightforward, conventional, and well-understood cases. Fatal pepper aspiration, abdominal injuries ranging from rents in the liver and spleen, transection of the pancreas, and traumatic pseudocysts of that organ are described here. The triad of signs dubbed the "tin ear syndrome" consists of bruising of the ear, retinal hemorrhages, and cerebral edema. Toxic ingestions, mainly of cocaine, and its related paraphernalia are described in addition to peculiar tissue-specific microwave oven burns, an inflicted injury that rational minds find hard to comprehend. Finally, the bizarre syndrome of Munchausen by proxy is reviewed, and some understanding of the dynamics of this disorder has begun. Knowledge about these diagnostic oddities will enable us to intervene and attempt to alter the outcome in these dysfunctional families. The authors would welcome other case reports of unusual manifestations of child abuse, neglect, and child sexual abuse. PMID- 2199922 TI - The neglect of our children. AB - When we consider all the manifestations of the effects of not meeting the basic needs of our children, we can feel nothing short of alarm and concern. The scope of the problem of child neglect, when the responsibility for this neglect is expanded beyond that of the parents or guardians, extends to inadequate health care, poor education, the ineffectiveness of the law, inadequate housing, and other adversities resulting from our social selection policies. PMID- 2199923 TI - Pediatric interview assessment of child abuse. Challenges and opportunities. AB - The assessment of child abuse is a professionally and personally challenging task. Here as elsewhere in medicine success often is linked with the informed intelligence, mature attitude, and professional demeanor of the clinician. If one can maintain a thoughtful and skeptical approach to the data; display warmth, calm, and respect to everyone involved in the case; and express one's views with care and parsimony, good information will be forthcoming and, it is hoped, excellent management will follow. PMID- 2199924 TI - Preparation for court testimony in child abuse cases. AB - Medical expert testimony in child abuse cases is a socially essential task if children are to be protected from abuse. Accomplishing this task in an excellent way is an important challenge requiring attention to its ethical, legal, and administrative aspects as well as to technical medical considerations. As the field of child protection matures as a medical specialty, expertise in child abuse becomes increasingly definable; it is now sufficiently definable to allow courts to begin to separate those physicians who are specialists in the field from those who are not. PMID- 2199925 TI - Education of the physician in child abuse. AB - Child abuse training often mirrors the development of the field of child abuse by focusing on identification and reporting at the expense of other topics. Physical abuse, and recently sexual abuse, have been emphasized, although neglect is more often reported. The training approach should also include information on epidemiologies, treatment, and prevention. A high index of suspicion can be taught by learning to identify specific physical and behavioral patterns of abuse, and discrepancies between history and the child's condition, and developing better interview skills. Physicians need to know reporting laws, what happens to reports in their community, and how to challenge adverse decisions. Characteristics of child abuse treatment and prevention programs should be taught to residents and physicians providing primary care to children. Principles of learning can be used with various methods to present child abuse information and skills. Whether educating medical students, general physicians, or child abuse experts, their level of involvement with child abuse and the key concepts appropriate for that level should be identified before training methods can be selected. Pediatricians can play an active role in assuring that education in child abuse occurs for all physicians. Answers to first set of questions: STEP 1. Probably middle class or higher. 2. Probably at least 5 years old. 3. Children should have at least average verbal and intellectual skills; they may need to be formally tested. 4. Parents should have at least average verbal and intellectual skills. Answers to second set of questions: Childhood Comes First 1. Approximately 1 year in many cases. 2. It should not; it is an individualized program. 3. No, but it should be an emotionally stable individual with good interactive skills and willing to make a substantial time commitment. 4. A wide range can be tolerated, but the coach will have to read if the consumer cannot. PMID- 2199926 TI - Pediatrician's role in preventing child maltreatment. AB - Pediatricians have the opportunity to play an important role in preventing child maltreatment. Major issues that influence pediatric practice in this area are discussed in this article. General ideas and specific strategies are presented to help guide the pediatrician's prevention efforts. PMID- 2199927 TI - [Dental prosthetic treatment of elderly patients]. AB - There seems to be an increasing need and demand for prosthetic treatment among old-age pensioners in Norway. The demand may be explained by more pensioners with own teeth, more interest in dental care, cosmetics, better information about treatment possibilities, and a better economy among the elderly. This article gives guidelines for various types of prosthetic treatment as respects for barriers such as chronic disease, aging, drugs, social isolation and for some elderly weak economy. Although prosthetic treatment of elderly differs little from that given to younger adults, the requirements of a tooth used as an abutment may be less strict in case of the elderly. PMID- 2199928 TI - Scanning skills. PMID- 2199931 TI - Cholesterol and the consumer. PMID- 2199929 TI - Developing skills in decision-making. PMID- 2199930 TI - Nurse education. How to use ... team teaching. PMID- 2199932 TI - The nursing shortage: dynamics and solutions. An overview. PMID- 2199933 TI - The nursing shortage: dynamics and solutions. Reflections on a recurring theme. AB - The passage of individual state nurse practice acts in the 1900s sharpened and focused attention on the practice and function of professional nurses. However, this had little effect on increasing the demand for nurses. In the 1930s student nurses were in ample supply. They staffed units in hospitals, and seniors served as charge or head nurses. It was World War II when one finally began to see the theme of nursing shortage emerge with a vengeance. The demand far exceeded the supply, creating a severe imbalance. The intervening next 4 decades brought forth many excellent models to minimize the shortage. Even the federal government contributed to the nursing shortage by offering opportunities for better-educated practitioners, teachers, and supervisors. Thus, as the nurse became better prepared, the demand for services increased. Several milestone studies are referenced during the 1970s and 1980s that attempted to balance the nursing shortage equation. The US objectives for the year 2000 provide specific guidelines as to what demands will be placed upon the nurse practitioner and educator. Can we meet those demands? Yes--with the full utilization of information technology to prepare the student and nurse practitioner to take advantage of this enormous information explosion. Will the nursing shortage continue to be a recurring theme? Yes! As nurses become better educated and ready for practice and patient-client problem solving, and as they provide strong voices in health policy formulation, the demands for their services will continue to far exceed the supply. PMID- 2199934 TI - The impact of corporate culture on nurse retention. AB - This article concerns the impact of the corporate culture of today's hospitals on the hospital's ability to attract and retain nurses. Several sources are used to illuminate recent sociohistoric changes that have had a profound impact on the business of health care and the professional world of staff nurses. Organizational characteristics that are associated with successful nurse retention strategies are offered. PMID- 2199935 TI - The nursing shortage: dynamics and solutions. The art of creative solutions. AB - The development and implementation of creative alternatives to minimize the overall effect of the nursing shortage is a national concern. This article examines the concept of creativity and suggests methods to generate creative ideas and solutions to this problem. PMID- 2199936 TI - The basics of laser technology. AB - As the use of laser systems increases, the nurse must be able to cope with the many changes that this new technology brings. An understanding of laser biophysics provides a foundation for laser safety. The nurse must also be aware of the organizational elements needed to provide a comprehensive laser program. Laser technology has definitely revolutionized modern health care delivery, and the nurse is instrumental in the continuing advancement of this science. PMID- 2199937 TI - Lasers in ophthalmology. AB - Lasers in ophthalmology have evolved tremendously during the last 3 decades. The laser is a valuable tool for the ophthalmologist today and will continue to be in the future. Currently, through laser technology advancements, vision is being maintained for some patients who would otherwise have severely impaired eye sight because of the lack of appropriate intervention. With the recent advances in excimer laser research, many patients may not have to wear glasses at all. Laser surgery is also minimizing the need for hospitalization and is offering a cost effective means of treatment for ophthalmologic conditions. Laser technology is indeed revolutionizing ophthalmology. PMID- 2199938 TI - Lasers in otolaryngology. AB - Otolaryngology has employed laser technology since the early 1970s for treatment of the ear, nasal and nasopharyngeal cavities, vocal cords, tongue, and oral mucosa. Perioperative nursing responsibilities center on preoperative education, intraoperative support, monitoring of a safe laser environment, and postoperative discharge management. PMID- 2199939 TI - Lasers in dermatology. AB - Although CO2, Nd:YAG, and argon wavelength lasers and a variety of other treatments have been used in an attempt to treat cutaneous vascular lesions, until the introduction of the yellow light lasers, a reliable treatment with few adverse effects was not available. The three models of yellow light lasers currently available offer various pulsing modes that permit treatment of superficial vascular lesions occurring on most external body surfaces. This wavelength also allows varying degrees of clearing of vascular lesions in children, adolescents, and adults. Areas not experiencing optimal clearing may be retreated, with the incidence of hypertrophic scarring, a common result of conventional therapy, markedly decreased. PMID- 2199940 TI - Lasers in general surgery. AB - Laser use in general surgery has become more popular in the past few years. The contact Nd:YAG laser returns tactile sensation to the surgeon and is used successfully to cut and coagulate during breast, colorectal, and biliary procedures. PMID- 2199941 TI - Lasers in gastroenterology. AB - The laser nurse is an integral part of the gastroenterologic endoscopy team. A keen awareness of laser instrumentation, delivery systems, endoscopy equipment, gastroenterologic conditions, perioperative endoscopy protocols, and patient monitoring are needed to provide safe and effective laser intervention. The success of gastroenterologic laser use is being realized as new applications begin to replace conventional methods of treatment. PMID- 2199942 TI - Lasers in urology. AB - A variety of lasers are used in medicine and surgery, and the three most common lasers are argon-ion, carbon dioxide, and Nd:YAG. All three lasers are used in urology because there has been demonstrated efficacy. The genitourinary system is vital to sustain life. The kidneys regulate most of the water in the body. Their main functions are to filter the blood impurities, drain off wastes and maintain the balance of essential chemicals in the body in liquid form. The filtration process is complex but practical. The nurse needs to understand the value of using the laser for a number of urologic procedures. The advantages are decreased blood loss, precision, less damage to surrounding tissue, ability to be used through endoscopes, and possible decreasing length of stay. The patient who presents with renal dysfunction must have an in-depth work-up. Preoperative assessment will include the patient's history, both current and past, laboratory studies, and radiologic examinations. Cystoscopy can be used as part of the work up and at the same time be used therapeutically. Assessment, planning, implementation, and evaluation do not change significantly from conventional procedures. The instrumentation, equipment, and supplies are the same with the addition of the laser and the various accessories. Laser lithotripsy has been an important adjunct to current therapy. The use of the laser for superficial bladder tumors has decreased the use of Foley catheters and the need to stay in the hospital. Other laser usage for external lesions has also proved to be efficacious. Patients entering the hospital system could benefit from a case management model of care. Case management uses critical paths to standardize managed care, facilitate discharge, promote cost-effective utilization of resources, and encourage collaborative practice, patient satisfaction, and professional satisfaction. PMID- 2199943 TI - Lasers in photodynamic therapy. AB - Photodynamic therapy has been shown to provide a reasonable alternative to other treatment modalities for patients with certain cancers, and in some cases may be the preferred treatment. Currently, photodynamic therapy is under FDA-approved clinical investigational trials in the treatment of tumors of the skin, bronchus, esophagus, bladder, head and neck, and of gynecologic and ocular tumors. Activation of a photosensitizer retained in the cancerous cells, by red light emitted from an argon-tunable dye laser system, produces a photochemical reaction that results in the selective destruction of tumor cells. Although the injected sensitizer results in patient photosensitivity lasting 4 to 8 weeks, there have been no reports of permanent side effects. This treatment can be delivered through fiberoptics--interstitially, endoscopically, retrobulbarly, and externally, and in most cases is performed under local anesthesia. Although this is a relatively new method for treatment of cancer, reports show great promise for palliation and potential cure in some cancer patients. PMID- 2199944 TI - Effects of met-enkephalin on the mechanical activity and distribution of met enkephalin-like immunoreactivity in the cat small intestine. AB - Naloxone-dependent effects of Met-enkephalin (10(-8) M) on the spontaneous and electrically induced mechanical activities were studied in longitudinal and circular preparations isolated from the cat duodenum, jejunum and ileum. Met Enkephalin changed the spontaneous activity of all preparations tested with the exception of the circular preparations from the ileum. Met-Enkephalin-induced responses of the longitudinal preparations from the ileum were abolished by treatment with tetrodotoxin (10(-7) M), while the responses of both longitudinal and circular preparations from the duodenum and jejunum were only partially depressed, being resistant to tetrodotoxin components. The latter were most pronounced in the duodenum. The neurogenic electrically induced (0.5 msec, 5 Hz, 150 pulses) responses of all the preparations consisted mainly of contractile components which were significantly and naloxone-dependently reduced by Met enkephalin (10(-8) M). The contractile components of the responses, which were reduced by Met-enkephalin, were entirely abolished by atropine (3 x 10(-6) M). Both Met-enkephalin and atropine inhibitory effects on the neurogenic responses were more pronounced in the ileum. Met-Enkephalin was found in nerve fibers of the myenteric plexus distributed mainly among the circular muscle. Single immunoreactive nerve fibers were observed in the longitudinal muscle layer of the duodenum but not in the jejunum and ileum. The distribution of Met-enkephalin like immunoreactivity along the small intestine did not show significant differences among the three intestinal regions tested. The results obtained suggest that Met-enkephalin can modulate the mechanical activity of the cat small intestine, inhibiting cholinergic transmission and/or activating smooth muscle opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2199945 TI - Differential regional distribution and release of two forms of gonadotropin releasing hormone in the chicken brain. AB - The functional significance of two molecular forms of gonadotropin-releasing hormone (GnRH) in the chicken brain was investigated. The differential distribution of [Gln8]GnRH (chicken GnRH-I, cGnRH-I) and [His5,Trp7,Tyr8]GnRH (chicken GnRH-II, cGnRH-II) was determined using high performance liquid chromatography and radioimmunoassay with region-specific antisera. Potassium stimulated release of immunoreactive cGnRH-I and cGnRH-II from brain regions was assessed in tissue incubations. cGnRH-I and cGnRH-II varied independently in different brain areas. The concentration of cGnRH-I was highest in the median eminence of the hypothalamus, and a small quantity was also detected in the midbrain and cerebrum. cGnRH-II was more widely distributed throughout the brain, with highest concentrations in areas of the hypothalamus outside the median eminence and in the medulla. Potassium stimulated the release of cGnRH-I from the median eminence 4-fold, while cGnRH-II release was not detectable. Neither cGnRH I nor cGnRH-II was released from the medulla. These data suggest: 1) cGnRH-I is the prime regulator of gonadotropin release from the pituitary, and 2) cGnRH-II may have a neurotransmitter or neuromodulator role in areas of the brain outside the median eminence. PMID- 2199946 TI - Insulin binding to brain capillaries is reduced in genetically obese, hyperinsulinemic Zucker rats. AB - In order to study the role of plasma insulin in regulating the binding of insulin to the endothelium of the blood-brain barrier (BBB), insulin binding to a purified preparation of brain capillaries was measured in both genetically obese Zucker rats and lean Zucker controls. We found a reduction of 65% in brain capillary insulin binding site number in the obese compared to lean rats with no change in receptor affinity. Furthermore, specific insulin binding to brain capillaries was negatively correlated (p less than 0.05) to the plasma insulin level, suggesting a role for plasma insulin in regulating insulin binding. A similar relationship was observed between insulin receptor number in liver membranes and the plasma insulin level. We conclude that obese, hyperinsulinemic Zucker rats exhibit a reduction in the number of BBB insulin receptors, which parallels the reduction seen in other peripheral tissues. Since insulin receptors have been hypothesized to participate in the transport of insulin across the BBB, the reduction observed in the obese rats may account for the decrease in cerebrospinal fluid insulin uptake previously demonstrated in these animals. PMID- 2199947 TI - Relative sparing of calcitonin gene-related peptide-containing primary sensory neurons following neonatal capsaicin treatment in the rat. AB - Calcitonin gene-related peptide (CGRP)-containing sensory neurons projecting to viscera or skin were detected by immunocytochemistry combined with fluorescent tracer in the dorsal root ganglia (Th9-10) of rats 5-6 weeks old treated neonatally with capsaicin. The number of CGRP-like immunoreactive (IR) cells were reduced by 50-60% with capsaicin treatment. Visceral CGRP-IR sensory neurons were shown to be more sensitive than cutaneous ones, which was also supported by the fact that CGRP-IR fibers in the stomach were completely diminished while epidermal CGRP-IR fibers were spared. PMID- 2199948 TI - Chromatographic and immunological evidence for mammalian GnRH and chicken GnRH II in eel (Anguilla anguilla) brain and pituitary. AB - Gonadotropin-releasing hormone (GnRH) peptides in the brain and pituitary of the European eel (Anguilla anguilla) were investigated by reverse phase high performance liquid chromatography (HPLC) and radioimmunoassay with region specific antisera. Two GnRH molecular forms were demonstrated in brain and pituitary extracts. One form eluted in the same position as synthetic mammalian GnRH on HPLC and was recognized by antibodies directed against the NH2 and COOH termini of mammalian GnRH as well as by antibodies to the middle region. The second form eluted in the same position as synthetic chicken GnRH II and was recognized by specific antibodies to this molecule. Salmon GnRH and chicken GnRH I were not detected. The occurrence of mammalian GnRH in teleost fish suggests that this molecular form is more ancient than was previously suspected and arose earlier than in primitive tetrapods, or that it has arisen in the eel through random mutation of salmon GnRH. The lack of salmon GnRH in the eel brain indicates that this molecular form is not common to all teleost species. The finding in eel brain of chicken GnRH II, which has previously been described in species of Mammalia, Aves, Reptilia, Amphibia, Osteichthyes, and Chondrichthyes, supports our hypothesis that this widespread structural variant may represent an early evolved and conserved form of GnRH. PMID- 2199949 TI - Chicken GnRH II occurs together with mammalian GnRH in a South American species of marsupial (Monodelphis domestica). AB - Two molecular forms of gonadotropin-releasing hormone (GnRH) were demonstrated in hypothalamic extracts of M. domestica using high performance liquid chromatography and radioimmunoassay with specific GnRH antisera. One form eluted in the same position as synthetic mammalian GnRH and was quantified equally by two mammalian GnRH antisera, while the second form coeluted with synthetic chicken GnRH II and was quantified equally with two chicken GnRH II antisera. The finding of chicken GnRH II in a South American species of marsupial, which has previously been reported in some Australian species of marsupial and in species of Aves, Reptilia, Amphibia, Osteichthyes and Chondrichthyes, supports our hypothesis that this widespread structural variant may represent an early evolved and conserved form of GnRH. PMID- 2199950 TI - Focal metabolic effects of angiotensin and captopril on subregions of the rat subfornical organ. AB - Angiotensin infusion increased glucose metabolism in 4 of 7 subdivisions of the rat subfornical organ, the effect being stronger in ventromedial compared to dorsolateral zones across the rostrocaudal axis. [Sar1-Leu8]Angiotensin II attenuated metabolic responses to intravenous angiotensin in all subfornical organ subregions. Brattleboro rats, having high circulating levels of angiotensin, displayed greater rates of glucose metabolism than Long-Evans rats in all subregions, differences that were eliminated by captopril, an inhibitor of angiotensin converting enzyme. The studies reveal focal subfornical organ zones where in vivo metabolic activity corresponds to cytoarchitectonic evidence for topographical processing within this angiotensin-sensitive structure. PMID- 2199951 TI - Are NPY and enkephalins costored in the same noradrenergic neurons and vesicles? AB - Separate studies show that NPY and enkephalins are widely distributed in peripheral noradrenergic neurons. In the present study, the subcellular costorage and release in response to intense sympathetic stimulation and reserpine at near therapeutic doses (0.05 mg/kg every other day) were examined. In young pig arteries and vas deferens, enkephalin and D beta H immunofluorescence show consistent but not total overlap. Also NPY is colocalized with D beta H in many fibers but with VIP (nonnoradrenergic) in others. Ultrastructural immunogold labeling indicates that individual terminals contain large dense cored vesicles (LDVs) which store either NPY or enkephalins, even though costorage of both peptides occurs. Some LDVs costore NPY and VIP, especially in the middle cerebral artery and in the lamina propria of vas deferens. Acute CNS ischemia depletes enkephalins and norepinephrine in all tissues analyzed without parallel loss of NPY. Reserpine depletes norepinephrine 70-85% but does not deplete NPY or enkephalins. The latter is in contrast to commonly used high doses known to produce nonspecific, detergent-like effects. In fact, low doses of reserpine induce a time-dependent new synthesis and processing of NPY precursor peptides in vas deferns. Contrasting effects of reserpine on NPY and enkephalin contents, new synthesis and apparent processing, and a differential response to acute CNS ischemia were found in every tissue studied. Activation of precursor neuropeptide processing occurred immediately upon intense sympathetic stimulation in most tissues. Dual localization of NPY in noradrenergic and nonnoradrenergic fibers and differences in subcellular LDV storage help explain why enkephalin correlates better than NPY with norepinephrine loss in response to acute CNS ischemia. Furthermore, the costorage of NPY and enkephalins in distinct subpopulations of noradrenergic fibers, which varies according to tissue, is likely to be under separate CNS control. PMID- 2199952 TI - Bombesin: potential integrative peptide for feeding and satiety. AB - The neuropeptide bombesin (BBS) is examined with regard to possible designation as an integrative peptide. The term integrative peptide has been proposed to distinguish a subset of regulatory peptides. These peptides, distributed in the body and the brain, may function as hormones and neurotransmitters to integrate physiological and psychological functions. It is suggested that BBS may function as a peripheral and central satiety-inducing agent. The specific topics with regard to BBS include: feeding, satiety, and aversion; peripheral and central effects; learning, memory, and reward; route of injection; taste modulation; gastrointestinal activity; neurotransmitter status; mechanism and neuroanatomical site of action; and neural and humoral transmission. PMID- 2199953 TI - Diagnostic evaluation of impotence. AB - A multispecialty approach to diagnosis of impotence is the most appropriate, because many factors may be at work. The expertise of professionals in the fields of urology, sex therapy, psychiatry, family practice, internal medicine, endocrinology, neurology, radiology, sleep evaluation, and vascular surgery may be needed to ascertain the correct organic or psychogenic cause in some cases. PMID- 2199954 TI - Treatment alternatives for impotence. AB - More than 10 million men in the United States are chronically impotent. Fortunately, significant advances have been made in psychotherapy, pharmacologic management, arterial and venous surgery, penile prosthesis implantation, and use of external devices so that most find a satisfactory solution. After their dysfunction is sufficiently evaluated and the most appropriate treatment option is applied, most men achieve erectile capability sufficient for intercourse. PMID- 2199955 TI - Stroke from alcohol and drug abuse. A current social peril. AB - Alcohol and drug abuse should be among the possible causes considered in cases of stroke, especially in young adults. As both are potentially remediable factors, primary care physicians may play an important role in the reduction of stroke by implementing educational and preventive measures among their young patients. PMID- 2199956 TI - Helping patients live with multiple sclerosis. What primary care physicians can do. AB - Patients with multiple sclerosis (MS) may experience progressive problems of many kinds, often over decades. Ambulation, muscle strength and coordination, bladder function, vision, behavior, and cognition may eventually be affected. The diagnosis is based on clinical features and laboratory studies, but no definitive test exists. The rate of misdiagnosis may be as high as 30%. Treatment consists of pharmacotherapy for symptoms, therapy for the disease itself, and experimental therapies. Long-term management of MS can be a worthwhile challenge for primary care physicians. Helpful resources include neurologists with an interest in the disease, regional treatment and rehabilitation centers, and local MS societies. PMID- 2199957 TI - Neutropenia in adults. What is its clinical significance? AB - Neutropenia remains a diagnostic and therapeutic challenge to primary care physicians. The clinical significance of neutropenia must always be interpreted within the context of the individual patient's presentation. Physicians who have an appreciation of the pathophysiologic mechanisms that produce neutropenia and familiarity with the commonly encountered clinical disorders can successfully evaluate and treat these conditions. PMID- 2199958 TI - Transient global amnesia. AB - Transient global amnesia is often attributed to a seizure, vascular cause, or migraine, but the outcome is usually benign. The presence of migraine and important risk factors for stroke necessitates close patient monitoring. Anti platelet therapy should be considered. PMID- 2199959 TI - The new antimicrobial agents. When they're the best choice and when they're not. AB - The number of antibiotics available to the clinician for treatment of infectious diseases continues to increase. However, choosing an agent just because it is new is not always cost-effective and may encourage the development of bacterial resistance. The site of infection, pharmacokinetic data, minimum inhibitory concentration, and cost must all be considered in selecting the optimal antimicrobial agent for a particular clinical situation. PMID- 2199960 TI - [Air pollution of indoor air]. PMID- 2199961 TI - [Change in liver size caused by antitubercular combination therapy]. AB - In 23 patients undergoing antituberculous combination treatment, an ultrasonographic study of the dimensions of the liver was carried out every two weeks for the first two to three months of treatment. Starting with the fourth to sixth week on the therapeutic regimen, significant increases in the width of the left, and the length of the right liver lobes amounting to an average of 1 cm (11%) were established. Differences in the time course of changes in liver size were not to be found, neither in connection with adverse reactions, nor as a function of sex. Between the age of the patient and the depth parameters of the right liver lobe, however, significant positive regressions were observed with the course of treatment. Patients older than 40 years experienced a more marked increase in liver size under therapy. Patients with a history of alcohol abuse and those with side effects, have, on average, larger livers. Slow acetylators manifest a slightly greater increase in the size of the liver during treatment than do rapid acetylators. None of the patients investigated revealed any clinically relevant hepatotoxic side effects. There was no strict correlation between transient transaminase elevations and ultrasonographic changes in the hepatic architecture. PMID- 2199962 TI - Introduction of an improved direct agglutination test for the detection of Leishmania infantum infection in southern France. AB - An improved direct agglutination test (DAT) is assessed for the detection of Leishmania infantum antibodies in man and in the canine reservoir in Southern France. The test performance in 32 human visceral leishmaniasis patients was in agreement with the parasitological diagnosis and the immunofluorescence (IFAT) results. In six patients diagnosed earlier as kala-azar cases, both DAT and IFAT revealed negative results. The specificity of the DAT was reproduced in this study by the absence of cross-reactions with sera from other patients. In the dog reservoir, the DAT results were compared with those obtained by IFAT, the enzyme linked immunosorbent assay (ELISA), cross-over electrophoresis and the latex agglutination test. All 34 dogs with parasitologically positive lymph node aspirates also had positive DAT titres (less than or equal to 1:640); the sensitivity in the other four tests was relatively low. Positive DAT and IFAT results were found in 16 unconfirmed cases of canine leishmaniasis, most probably due to prepatent L. infantum infections. PMID- 2199963 TI - Endovascular surgery: an overview. AB - Endovascular surgery, a new discipline for the treatment of vascular disease, is still in its infancy. Techniques consist of procedures that open total obstructions or partial stenosis of the vascular system and are for the most part in clinical trials. Balloon angioplasty, angioscopy, mechanical atherectomy and laser angioplasty are the major techniques in endovascular surgery. This article describes procedures, the techniques and complications. PMID- 2199964 TI - Expression of and response to growth regulatory peptides by two human pancreatic carcinoma cell lines. AB - Two human pancreatic adenocarcinoma cell lines (PANC 1 and MIA PACA 2) were examined for expression of growth factors that could potentially play a role either in growth regulation of the tumor cells, or in cells that comprise the stromal elements of tumors. Both cell lines expressed transforming growth factor alpha (TGF alpha), basic fibroblast growth factor (bFGF), c-sis (PDGF B chain), TGF beta 1, and TGF beta 3 mRNA by Northern blot analysis. Only the PANC 1 cells, however, expressed the TGF beta 2 transcript. TGF beta-like competing activity was found in medium conditioned by either cell line, but TGF alpha-like [epidermal growth factor (EGF)-competing] activity was not detected in the medium from either cell line by radioreceptor assay. TGF alpha and EGF caused concentration-dependent stimulation of soft agar colony growth of the MIA PACA 2 cells, while only TGF alpha caused a significant but less dramatic stimulation of soft agar growth of the PANC 1 cells. Insulin stimulated the anchorage independent growth of MIA PACA 2 but not PANC 1 cells. Likewise, bFGF also caused a concentration-dependent stimulation of MIA PACA 2 but not PANC 1 growth in soft agar, and PDGF had no effect on the growth of either cell line. TGF beta had no inhibitory or stimulatory effect on soft agar colony growth of either the PANC 1 or the MIA PACA 2 cells, although both cell lines exhibited high affinity, saturable TGF beta binding sites, and TGF beta 1 was capable of autoinduction of TGF beta 1 mRNA expression in PANC 1 cells. The ability to continue to respond to positive growth regulatory factors coupled with the loss of responsiveness to negative growth factors may be important in the pathogenicity of these aggressive tumors. PMID- 2199965 TI - Growing pancreatic acinar cells (postpancreatitis and fetal) express a ductal antigen. AB - Monoclonal antibodies specific for luminal plasma membranes of acinar and duct cells of the exocrine pancreas were used to investigate changes in antigen expression during regeneration of the pancreas after acute pancreatitis and during fetal pancreatic development in mice. During regeneration after acute pancreatitis induced by supramaximal injections of cerulein or by a choline deficient, ethionine-supplemented diet, morphologically identifiable acinar cells expressed the ductal antigen on their luminal surface, but at a lower level than this antigen is expressed on duct cells. As the pancreas regenerated, the ductal antigen was lost from acinar cells and was found only on duct cells. Characteristic tubular complexes formed in both pancreatitis models and were positive for the acinar antigen, demonstrating their acinar origin. In fetal pancreas, acinar cells between prenatal days 3 through 1, when zymogen granules were already abundant, expressed the duct-cell antigen on their luminal surface. By birth duct antigen was mostly present on ducts with only occasional label on acinar cells. The presence of a ductal antigen on acinar cells is associated with acinar-cell growth during regeneration and during fetal development and may reflect a less differentiated state. PMID- 2199966 TI - Role of gastric juice in feedback regulation of rat pancreatic secretion by luminal proteases. AB - The role of gastric juice in the intestine on the pancreatic secretory response to intraduodenal infusion of trypsin inhibitors or to diversion of bile and pancreatic juice from the intestine was studied in conscious rats with pylorus ligation and gastric juice drainage. In absence of gastric juice in the intestine, diversion of bile and pancreatic juice from the intestine stimulated pancreatic secretion, but the incremental protein and fluid secretory responses to diversion of bile and pancreatic juice were increased approximately 2.9-fold and 2.5-fold, respectively, by intraduodenal infusion of HCl (60 microEq/h). Intraduodenal infusion of HCl (240 microEq/h) had no effect on the pancreatic secretory response to infusion of lima bean trypsin inhibitor (20 mg). These results support the hypothesis that the inhibitory effect of atropine on the pancreatic secretory response to diversion of pancreatic juice or bile and pancreatic juice is secondary to inhibition of gastric acid secretion. The lack of effect of HCl on the pancreatic response to trypsin inhibitor contradicts the hypothesis that acid in the intestine is important or necessary for the feedback response to loss of intraluminal protease activity. It is proposed that acid in the intestine augments the pancreatic response to diversion of pancreatic juice or bile and pancreatic juice by reducing intraluminal pH and thereby inactivating residual pancreatic proteases. PMID- 2199967 TI - Influence of naloxone, atropine, and metoclopramide on ethanol augmentation of insulin secretion after intravenous glucose stimulation. AB - The effect of naloxone (opiate antagonist), atropine (muscarinic antagonist), and metoclopramide (dopamine antagonist) upon ethanol augmentation of insulin secretion after intravenous glucose stimulation was studied in 19 young healthy subjects. Intravenous glucose tolerance tests were performed with and without pretreatment with oral ethanol. The effect of naloxone, atropine, and metoclopramide on insulin secretion was investigated in six, six, and seven subjects, respectively. Ethanol pretreatment was followed by increased insulin (p less than 0.001) and C-peptide areas (p less than 0.01) after intravenous glucose (0-10 min), indicating that ethanol augments insulin secretion. Neither antagonism with naloxone nor with atropine or metoclopramide was able to suppress the ethanol augmentation of insulin secretion. The decline in glucagon concentration normally seen after intravenous glucose administration was partially prevented by ethanol pretreatment. PMID- 2199968 TI - Glucagon and the glucagon-like peptides. AB - Glucagon and the glucagon-like peptides are encoded within a larger precursor, proglucagon. The proglucagon gene is expressed in the pancreas, intestine, and brain, giving rise to a single proglucagon mRNA transcript that is identical in all tissues. Tissue-specific posttranslational processing of proglucagon accounts for the different molecular forms of the glucagon-related peptides present in each tissue. Glucagon-like peptide I has been demonstrated to have potent insulinotropic properties, but the biological importance of other glucagon related peptides remains unclear. The recent advances that have increased our understanding of the biology of glucagon and the glucagon-like peptides are reviewed. PMID- 2199969 TI - Complete agenesis of the dorsal pancreas--a case report and review of the literature. AB - A case of agenesis of the dorsal pancreas associated with diabetes mellitus and dilated biliary trees was reported. Preoperative diagnosis was made by endoscopic retrograde cholangiopancreatography and computed tomography. Laparotomy revealed a normal head of the pancreas but complete agenesis of the body and tail. Biopsy specimens removed from the head showed normal pancreatic tissue but only fat tissue from the presumed body and tail. This anomaly has rarely been reported in the literature. A thorough review of the literature was made and consideration of differential diagnosis was discussed. PMID- 2199970 TI - Functionally acceptable substitutions in two alpha-helical regions of lambda repressor. AB - A method of targeted random mutagenesis has been used to investigate the informational content of 25 residue positions in two alpha-helical regions of the N-terminal domain of lambda repressor. Examination of the functionally allowed sequences indicates that there is a wide range in tolerance to amino acid substitution at these positions. At positions that are buried in the structure, there are severe limitations on the number and type of residues allowed. At most surface positions, many different residues and residue types are tolerated. However, at several surface positions there is a strong preference for hydrophilic amino acids, and at one surface position proline is absolutely conserved. The results reveal the high level of degeneracy in the information that specifies a particular protein fold. PMID- 2199971 TI - Functional interaction among catalytic residues in subtilisin BPN'. AB - Variants of the serine protease, subtilisin BPN', in which the catalytic triad residues (Ser-221, His-64, and Asp-32) are replaced singly or in combination by alanine retain activities with the substrate N-succinyl-L-Ala-L-Ala-L-Pro-L-Phe-p nitroanilide (sAAPF-pna) that are at least 10(3) to 10(4) above the non-enzymatic rate [Carter, P., Wells, J.A. Nature (London) 322:564-568, 1988]. A possible source of the residual activity was the hydrogen bond with the N delta 2 of Asn 155 that helps to stabilize the oxyanion generated in the tetrahedral transition state during amide bond hydrolysis by the wild-type enzyme. Replacing Asn-155 by Gly (N155G) lowers the turnover number (kcat) for sAAPF-pna by 150-fold with virtually no change in the Michaelis constant (KM). However, upon combining the N155G and S221A mutations to give N155G:S221A, kcat is actually 5-fold greater than for the S221A enzyme. Thus, the catalytic role of Asn-155 is dependent upon the presence of Ser-221. The residual activity of the N155G:S221A enzyme (approximately 10(4)-fold above the uncatalyzed rate) is not an artifact because it can be completely inhibited by the third domain of the turkey ovomucoid inhibitor (OMTKY3), which forms a strong 1:1 complex with the active site. The mutations N155G and S221A individually weaken the interaction between subtilisin and OMTKY3 by 1.8 and 2.0 kcal/mol, respectively, and in combination by 2.1 kcal/mol. This is consistent with disruption of stabilizing interactions around the reactive site carbonyl of the OMTKY3 inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2199972 TI - Crystal structures of subtilisin BPN' variants containing disulfide bonds and cavities: concerted structural rearrangements induced by mutagenesis. AB - The X-ray structures of four genetically engineered disulfide variants of subtilisin have been analyzed to determine the energetic and structural constraints involved in inserting disulfide bonds into proteins. Each of the engineered disulfides exhibited atypical sets of dihedral angles compared with known structures of natural disulfide bridges in proteins and affected its local structural environment to a different extent. The disulfides located in buried regions, Cys26-Cys232 and Cys29-Cys119, induced larger changes than did Cys24 Cys87 and Cys22-Cys87, which are located on the surface of the molecule. An analysis of the concerted changes in secondary structure units such as alpha helices and beta-sheets indicated systematic long-range effects. The observed changes in the mutants were largely distributed asymmetrically around the inserted disulfides, reflecting different degrees of inherent flexibility of neighboring secondary structure types. The disulfide substitution in each variant molecule created some invaginations or cavities, causing a reorganization of the surrounding water structure. These changes are described, as well as the changes in side chain positions of groups that border the cavities. PMID- 2199973 TI - Crystal structure of myoglobin from a synthetic gene. AB - Crystals have been grown of myoglobin produced in Escherichia coli from a synthetic gene, and the structure has been solved to 1.9 A resolution. The space group of the crystals is P6, which is different from previously solved myoglobin crystal forms. The synthetic myoglobin is essentially identical to myoglobin isolated from sperm whale tissue, except for the retention of the initiator methionine at the N-terminus and the substitution of asparagine for aspartic acid at position 122. Superposition of the coordinates of native and synthetic sperm whale myoglobins reveals only minor changes in the positions of main chain atoms and reorientation of some surface side chains. Crystals of variants of the "synthetic" myoglobin have also been grown for structural analysis of the role of key amino acid residues in ligand binding and specificity. PMID- 2199974 TI - Patterns of mutational sensitivity to chemicals in poststem-cell stages of mouse spermatogenesis. PMID- 2199975 TI - Multiple endpoint mutational analysis in the mouse. PMID- 2199976 TI - hprt mutations in vivo in human T-lymphocytes: frequencies, spectra and clonality. PMID- 2199977 TI - Mouse models for understanding human developmental anomalies. PMID- 2199978 TI - The current status of two-dimensional electrophoresis in germ cell mutation research. PMID- 2199979 TI - Analysis of DNA sequences in individual gametes: application to human genetic mapping. PMID- 2199980 TI - Mouse mutational data in the estimation of human risk. PMID- 2199981 TI - Some problems and considerations in the assessment of genetic risks of exposure to ionizing radiation. PMID- 2199982 TI - Immunologic methods for the detection of carcinogen adducts in humans. AB - Monoclonal antibodies have been developed which recognize a number of carcinogen DNA and protein adducts. These antibodies can be used in highly sensitive competitive enzyme linked immunosorbent assays (ELISA) to detect femtomole levels of adducts in human samples. With the most sensitive antibodies, DNA adducts in the range of 1/10(8) nucleotides can be measured. In addition, antibodies to DNA adducts can be used to investigate immunohistochemically the localization of adducts in specific cell and tissue types. Antibodies recognizing benzo(a)pyrene diol epoxide-DNA have been used to monitor adducts in white blood cell DNA of foundry workers and placental and white blood cell DNA of smokers and nonsmokers. Because of antibody crossreactivity with structurally related adducts of other polycyclic aromatic hydrocarbons, this assay is not specific for benzo(a)pyrene adducts. Antibodies to the stable guanine imidazole ring opened aflatoxin-B1-DNA adduct have been used to detect elevated levels of adducts in liver tissue from Taiwanese hepatocellular cancer patients. Monoclonal antibodies against 8 methoxypsoralen-DNA have been used to monitor adducts in psoriasis and cancer patients treated with psoralen plus UVA light. These patients have also served as model systems for the development of immunofluorescence methods for adduct detection. Immunohistochemical staining of skin biopsies from psoriasis patients demonstrated specific staining of epidermal cells. With further increases in sensitivity, this method should be applicable to the detection of adducts in other human tissues. Adduct detection in humans is now established as a viable method for determination of exposure to certain chemical carcinogens. However, the relationship of adduct measurements to individual risk requires further investigation. PMID- 2199983 TI - Human DNA adducts due to smoking and other exposures to carcinogens. PMID- 2199984 TI - The role of protein adducts in the study of chemical carcinogenesis. PMID- 2199985 TI - Comparison of human and rodent response to genotoxicants. PMID- 2199986 TI - Alcohol and aldehydes. PMID- 2199987 TI - The glycophorin A assay for somatic cell mutations in humans. PMID- 2199988 TI - Mouse model for somatic mutation at the HPRT gene: molecular and cellular analyses. PMID- 2199989 TI - Structure evolution and processing adaptation of neurohypophysial hormone neurophysin precursors. PMID- 2199990 TI - Aromatization and estrogen action in brain. PMID- 2199991 TI - Evolution and adaptation of gonadotropin receptors. PMID- 2199992 TI - Molecular structures of some vertebrate-type messenger peptides in invertebrates. PMID- 2199993 TI - The possibilities of recombinant DNA technology for the elucidation of the structure of steroid receptors and their mode of action. PMID- 2199994 TI - Evolution of growth hormone and prolactin receptors and effectors. PMID- 2199995 TI - Role of intracellular messengers in the regulation of juvenile hormone biosynthesis in the cockroach, Diploptera punctata. PMID- 2199996 TI - Growth hormone and thyroid hormone levels during smolting in different populations of Atlantic salmon. PMID- 2199997 TI - Insulin action and insulin receptors in embryogenesis of vertebrates and invertebrates. PMID- 2199998 TI - Hormonal control of molting in crustaceans. PMID- 2199999 TI - Prolactin and synlactin: comparative aspects. PMID- 2200001 TI - Neuropeptides in annelids. PMID- 2200000 TI - Dopamine and male/female differentiation in a hermaphroditic polychaete (Ophryotrocha puerilis). PMID- 2200002 TI - The caudal neurosecretory system: quest and bequest. PMID- 2200003 TI - Pancreatic polypeptide (PP) and its relevant relatives. PMID- 2200004 TI - Evolution of chordate endocrine organs. PMID- 2200005 TI - Adipokinetic hormones: structures and functions. PMID- 2200007 TI - Morphological, biochemical, and physiological studies on insect enkephalins. PMID- 2200006 TI - Subcommissural organ and cerebrospinal fluid: a biochemical and experimental study. PMID- 2200008 TI - The eclosion hormone system: an example of coordination of endocrine activity during the molting cycle of insects. PMID- 2200009 TI - In situ hybridization techniques in the study of endocrine secretions. PMID- 2200010 TI - Immunochemistry and comparative insect (neuro) endocrinology. PMID- 2200011 TI - The neuroendocrine system of flatworms. PMID- 2200012 TI - Hormonal control of sperm production in teleost fish. PMID- 2200013 TI - The yolk proteins and their genes in Drosophila. PMID- 2200014 TI - Vertebrate vitellogenesis: molecular model for multihormonal control of gene regulation. AB - The stimulation of yolk protein synthesis by estrogen is a characteristic of female non-mammalian vertebrates; in mammals, however, vitellogenesis has been suppressed as a corollary of the evolution of viviparity. It is our hypothesis that progesterone has a dual role in this phylogenetic trend; a) to inhibit myometrial contraction and thus set the stage for internal development of embryos and associated placentation, b) to inhibit yolk protein synthesis as placentation became an efficient direct supply of nutrients to the fetus. We have presented evidence that in the reptiles, the central vertebrate group from which the ancestors of modern mammals evolved, the control of yolk protein synthesis is complex, involving both pituitary and ovarian steroids (estradiol, testosterone and progesterone). This system provides an excellent model for the multihormonal contents of gene regulation involving both + and - controls. PMID- 2200015 TI - Functions of salmon pituitary glycoprotein hormones: "the maturational surge hypothesis". PMID- 2200016 TI - Hormonal control of arthropod reproduction. PMID- 2200017 TI - Endocrine control of annelid reproduction. PMID- 2200018 TI - Endocrine control of oocyte maturation in teleosts. PMID- 2200019 TI - The life cycle of the brain-pituitary-gonad-axis in teleosts. PMID- 2200020 TI - Intracellular events associated with GnRH and dopamine effects on GTH secretion in tilapia. PMID- 2200021 TI - Thyroid function in poikilotherms. PMID- 2200022 TI - Hormonal control of peripheral monodeiodination in vertebrates. PMID- 2200023 TI - Regulation of pituitary thyrotropin secretion. AB - The pituitary thyrotropin secreting cells of tetrapods share a common responsiveness to TRH, but the specificity of this response may differ among species. TSH responses in amphibians and reptiles appear to be somewhat less specific than in mammals, but each group differs in responsiveness to particular neuropeptides, and it is not clear that TRH is the main regulator of TSH in nonmammalian species. It is not yet known whether these diverse peptides are acting directly on the thyrotrope or possibly through a paracrine mechanism. A CRH-like peptide may be a common neuroregulator of the anuran thyroid and interrenal in metamorphosis. Inhibitory regulation including effects of neuropeptides and thyroid feedback at the pituitary level is evident in reptiles, but is not known for other nonmammalian groups. In ectotherms, the potential actions of temperature on TSH secretion must also be considered. In this regard, it is important to recognize that the thermal relations of the thyrotropin response may be distinct from other pituitary hormones, as well as other components of the hypothalamo-pituitary-thyroid axis (Licht et al., 1989). PMID- 2200025 TI - Corticosteroid function: evolutionary aspects. PMID- 2200024 TI - Comparative studies of thyroid hormone deiodinase systems. PMID- 2200026 TI - Hormones and stress in birds: activation of the hypothalamo-pituitary-adrenal axis. PMID- 2200027 TI - Stress in reptiles. PMID- 2200028 TI - Evolutionary aspects of corticotropin releasing hormones. PMID- 2200029 TI - Evolution of prolactin and growth hormone family. PMID- 2200030 TI - Phylogenetic patterns of the endocrine pancreas. PMID- 2200031 TI - Aspects of hormonal control of osmoregulation in desert marsupials. PMID- 2200032 TI - The role of antidiuretic hormone in the regulation of glomerular filtration rate in birds. PMID- 2200033 TI - The renin-angiotensin system and glomerular function of teleost fish. PMID- 2200034 TI - The tilapia prolactin cell--twenty-five years of investigation. PMID- 2200035 TI - Genealogy of the GnRH family. PMID- 2200036 TI - Recent advances in hormonal regulation of water metabolism in terrestrial insects. PMID- 2200037 TI - Roles of prolactin in salmonids. PMID- 2200038 TI - Glomerular filtration dynamics in reptiles: endocrine effects. PMID- 2200039 TI - Hypocalcin physiology. PMID- 2200040 TI - Calcium homeostasis in avian species. PMID- 2200041 TI - Prostaglandins and reproduction in reptiles. PMID- 2200042 TI - Evolutionary aspects of prostaglandins and other eicosanoids in invertebrates. PMID- 2200043 TI - Photoperiodic control of teleost reproduction. PMID- 2200044 TI - Seasonal breeding in two marsupials, the bandicoot Isoodon macrourus and the possum Trichosurus vulpecula. PMID- 2200045 TI - Endogenous-exogenous interactions in circannual rhythms. PMID- 2200046 TI - Modification of pubertal photoperiodic responses in rodents by factors acting during fetal development. PMID- 2200047 TI - Control of seasonal reproduction in the Tammar and Bennett's wallabies. PMID- 2200048 TI - Glucagon and related peptides (an overview). PMID- 2200049 TI - Current status of behavioural endocrinology in tropical marine teleosts. PMID- 2200050 TI - Neuroendocrine control of prolactin and incubation behavior in gallinaceous birds. PMID- 2200051 TI - Field endocrinology of reptiles: hormonal control of alternative male reproductive tactics. PMID- 2200052 TI - Androgens and dominance in higher vertebrates. PMID- 2200053 TI - The occurrence of ecdysteroids in vertebrates infected with helminths. PMID- 2200055 TI - Neurohormonal peptides in parasitic worms: a new frontier in host-parasite pathophysiology. PMID- 2200054 TI - Occurrence and possible significance of developmental hormones in nematodes. PMID- 2200056 TI - Gonadotropin-releasing hormone in primitive fishes. PMID- 2200057 TI - Structure and regulation of secretion of mouse placental lactogens. PMID- 2200058 TI - Mammalian Phe-Met-Arg-Phe-NH2-like peptides: structure, biological activity and distribution. PMID- 2200059 TI - Brain aromatization of testosterone regulates male reproductive behavior in birds. PMID- 2200060 TI - [Enzymatic peptide synthesis--a review]. PMID- 2200061 TI - [The position of the history of pharmacies within the history of pharmacy]. PMID- 2200062 TI - [In vitro model systems for the evaluation of absorption from the gastrointestinal tract]. PMID- 2200063 TI - [Species variations of receptor-effector parameters: a solvable problem of drug research]. PMID- 2200064 TI - Effect of beta-sitosterol-3-beta-D-glucoside on insulin secretion in vivo in diabetic rats and in vitro in isolated rat islets of Langerhans. AB - Beta-Sitosterol-3-beta-D-glucoside (1) has been reported to be the active antidiabetic agent of Centaurea seridis L. var. maritima. The present study examines the effect of oral administration of this compound on plasma insulin and glucose levels in streptozotocin-induced diabetic rats and its influence on insulin release from isolated rat islets. The results indicate that 1 did not change insulin and glucose levels in rats with severe diabetes. 1 stimulated insulin release from isolated rat islets in the presence of a non-stimulatory glucose concentration but did not increase the insulin releasing capacity of glucose (16 mmol/l). These data suggest that 1 exerts its action on intact pancreatic beta-cells by stimulating insulin secretion. PMID- 2200065 TI - Synthesis of some new trisubstituted derivatives of 2,4,6-trichloro-1,3,5 triazine and their anti-bacterial activity. PMID- 2200066 TI - Assessment of psychotropic drug utilization and adverse reactions in the Federal Republic of Germany. PMID- 2200067 TI - Clinical trials in Europe and the development of new psychotropics as viewed by European manufacturers. AB - A number of external and internal (industry-specific) difficulties and problems related to clinical trials and the development of new psychotropics in Europe, are reviewed. These can be classified into 3 interdependent categories of problems: 1. strategy-related; 2. implementation-related; 3. time-related. Apart from ethical and methodological issues, the external problems are: a) diversity of country-specific regulations and requirements for registration and drug approval; b) differences in culture, traditions, education and training background of investigators and patients; c) high competition for good trial centers; d) increasing pressure and negative attitude from public media with respect to clinical testing of drugs. In the strategic planning of the development of a new drug, resources and heavy/costly logistic commitments for each individual study have to be taken into consideration. For the manufacturers it is therefore imperative to fix the plans and the kind of the studies to be performed sometimes several years in advance. Conflict often arises with respect to the developmental changes, both in environmental conditions and in the state of the art. Implementation of the clinical, particularly multicenter/multinational trials poses problems of multilingual documentation, heavy logistics of drug supply, quality control and monitoring of the studies. Inherent to these European problems is a unproportional high time expenditure which has important consequences for scientific progress and economy. Possible solutions for these problems are discussed. The initial steps in this direction will be the establishment of European standards for clinical trials, and uniform requirements for drug registration and approval. PMID- 2200068 TI - Consensus Conference on the Methodology of Clinical Trials of "Nootropics", Munich, June 1989. Report of the Consensus Committee. PMID- 2200069 TI - Hyperbaric oxygen therapy--an overview. PMID- 2200070 TI - Genetic transmission of major affective disorders: quantitative models and linkage analyses. AB - We comprehensively reviewed 2 types of studies aimed at specifying the mode of inheritance of major affective disorders: quantitative models and linkage analyses. Quantitative models attempt to represent the genetic mechanism responsible for the familial distribution of a disorder. Despite efforts to refine models by incorporating the bipolar-unipolar distinction or the sex effect, consistent support for a specific mode of transmission has not been found. Some mixed genetic models support single major locus inheritance, but transmission probabilities do not conform to Mendelian expectations. Linkage analysis is a more powerful technique used for testing the single gene hypothesis. Linkage results have also been inconsistent, showing moderate support for an X-linked variant of bipolar-related disorder and equivocal support for linkages to Chromosomes 6 and 11. However, relatively few genetic loci have been examined. Methodological factors, genetic heterogeneity, and phenotypic heterogeneity are discussed as potential explanations for inconsistent findings. PMID- 2200071 TI - Using the longitudinal Guttman simplex as a basis for measuring growth. AB - Many difficulties inherent in the measurement of growth stem from the use of traditional measurement methodologies. The longitudinal Guttman simplex (LGS), an alternative approach based on a model of growth, is discussed in this article. The LGS has several advantages over traditional methodology. First, interindividual differences in developmental rates are a part of the model. Second, the LGS procedure can easily handle any number of occasions of measurement. Third, the LGS is suited to nonlinear as well as linear monotonic growth. Fourth, a consistency index associated with the LGS methodology, CL, indicates the extent to which cumulative, unitary development characterizes a particular latent variable. Finally, and perhaps most important, because a model of the growth undergone by the latent variable being measured is incorporated in the LGS model the resulting instruments enjoy a high level of construct validity. The LGS is limited to cumulative, unitary development; additional measurement theories are needed for other kinds of development. PMID- 2200072 TI - Psychotherapy for the treatment of depression: a comprehensive review of controlled outcome research. AB - Previous quantitative reviews of research on the efficacy of psychotherapy for depression have included only a subset of the available research or limited their focus to a single outcome measure. The present review offers a more comprehensive quantitative integration of this literature. Using studies that compared psychotherapy with either no treatment or another form of treatment, this article assesses (a) the overall effectiveness of psychotherapy for depressed clients, (b) its effectiveness relative to pharmacotherapy, and (c) the clinical significance of treatment outcomes. Findings from the review confirm that depressed clients benefit substantially from psychotherapy, and these gains appear comparable to those observed with pharmacotherapy. Initial analysis suggested some differences in the efficacy of various types of treatment; however, once the influence of investigator allegiance was removed, there remained no evidence for the relative superiority of any 1 approach. In view of these results, the focus of future research should be less on differentiating among psychotherapies for depression than on identifying the factors responsible for improvement. PMID- 2200073 TI - Children of depressed parents: an integrative review. AB - This article reviews the various literatures on the adjustment of children of depressed parents, difficulties in parenting and parent-child interaction in these families, and contextual factors that may play a role in child adjustment and parent depression. First, issues arising from the recurrent, episodic, heterogeneous nature of depression are discussed. Second, studies on the adjustment of children with a depressed parent are summarized. Early studies that used depressed parents as controls for schizophrenic parents found equivalent risk for child disturbance. Subsequent studies using better-defined samples of depressed parents found that these children were at risk for a full range of adjustment problems and at specific risk for clinical depression. Third, the parenting difficulties of depressed parents are described and explanatory models of child adjustment problems are outlined. Contextual factors, particularly marital distress, remain viable alternative explanations for both child and parenting problems. Fourth, important gaps in the literature are identified, and a consistent, if unintentional, "mother-bashing" quality in the existing literature is noted. Given the limitations in knowledge, large-scale, long-term, longitudinal studies would be premature at this time. PMID- 2200074 TI - Is eye movement dysfunction a biological marker for schizophrenia? A methodological review. AB - There is a high prevalence of eye movement dysfunction (EMD) in persons with schizophrenia and their first-degree relatives. Studies addressing the prevalence, stability, familial transmission, and psychological correlates of EMD in persons from both psychiatric and general populations offer suggestive evidence that this abnormality may serve as a biological marker for schizophrenia. Although these findings are promising, their significance for elucidating the diagnostic bandwidth, pathophysiology, and genetics of this disorder remains to be determined. More precise characterization of ocular motility, perhaps when used in conjunction with global measures of pursuit adequacy, may be essential for clarifying the pathophysiological and genetic significance of EMD for schizophrenia. Recent research efforts are beginning to identify particular abnormalities that could serve as more specific biological markers for schizophrenia. PMID- 2200075 TI - On the control of automatic processes: a parallel distributed processing account of the Stroop effect. AB - Traditional views of automaticity are in need of revision. For example, automaticity often has been treated as an all-or-none phenomenon, and traditional theories have held that automatic processes are independent of attention. Yet recent empirical data suggest that automatic processes are continuous, and furthermore are subject to attentional control. A model of attention is presented to address these issues. Within a parallel distributed processing framework, it is proposed that the attributes of automaticity depend on the strength of a processing pathway and that strength increases with training. With the Stroop effect as an example, automatic processes are shown to be continuous and to emerge gradually with practice. Specifically, a computational model of the Stroop task simulates the time course of processing as well as the effects of learning. This was accomplished by combining the cascade mechanism described by McClelland (1979) with the backpropagation learning algorithm (Rumelhart, Hinton, & Williams, 1986). The model can simulate performance in the standard Stroop task, as well as aspects of performance in variants of this task that manipulate stimulus-onset asynchrony, response set, and degree of practice. The model presented is contrasted against other models, and its relation to many of the central issues in the literature on attention, automaticity, and interference is discussed. PMID- 2200076 TI - Emotion, attention, and the startle reflex. AB - This theoretical model of emotion is based on research using the startle-probe methodology. It explains inconsistencies in probe studies of attention and fear conditioning and provides a new approach to emotional perception, imagery, and memory. Emotions are organized biphasically, as appetitive or aversive (defensive). Reflexes with the same valence as an ongoing emotional state are augmented; mismatched reflexes are inhibited. Thus, the startle response (an aversive reflex) is enhanced during a fear state and is diminished in a pleasant emotional context. This affect-startle effect is not determined by general arousal, simple attention, or probe modality. The effect is found when affects are prompted by pictures or memory images, changes appropriately with aversive conditioning, and may be dependent on right-hemisphere processing. Implications for clinical, neurophysiological, and basic research in emotion are outlined. PMID- 2200077 TI - The role of contingency in classical conditioning. AB - The assumption that classical conditioning depends on a contingent relation between the conditioned stimulus (CS) and the unconditioned stimulus (US), which was proposed some decades ago as an alternative to the traditional contiguity assumption, still is widely accepted as an empirical generalization, if no longer as a theoretical postulate. The first support for the contingency assumption was provided by experiments in which occasional CS-US pairings produced no response to the CS in random training--i.e., training in which the probability of the US was the same in the presence and absence of the CS. Those early experiments, the results of which too often are taken at face value, are reconsidered along with various later experiments that show conditioning, both of the CS and its context, in random training. The evidence suggests that CS-US contingency is neither necessary nor sufficient for conditioning and that the concept has long outlived any usefulness it may once have had in the analysis of conditioning. PMID- 2200078 TI - [Serum levels of salicylic acid in patients with psoriasis treated with 10% salicylic acid ointment]. AB - Ten patients with psoriasis were treated for three days with salicylic acid ointment with vaseline vehicle. In all patients the serum concentration of salicylic acid increased systematically and the concentration depended on the amount of ointment used and on psoriasis form. Only in one case of exudative psoriasis the level of salicylic acid reached the value causing intoxication, and produced a diffuse inflammatory erythema with itching. The treatment caused no changes of biochemical indices. PMID- 2200079 TI - [Levamisole in the treatment of crural ulcers]. AB - In a clinical study on 74 patients with 102 crural ulcers levamisole 150 mg was given for 1 or 2 successive days daily during 3 to 17 weeks, besides conventional treatment. The method seems to raise the per cent of favourable therapeutic results in such cases. Drug tolerance was good and no dangerous complications were observed in any case. PMID- 2200080 TI - [Sigmund Freud's "splendid isolation". Materials for critical review of psychoanalytic historiography]. AB - On the basis of the published critical reviews of Freud's works one may evaluate the extent and intensity of the scholarly reception given to psychoanalysis. Traditional views stressing the early academic isolation of psychoanalysis must be revised. The same is true of the radically opposite positions of modern American scientific historiography. PMID- 2200081 TI - [Inciting the masses under national socialism. A sociopsychologic analysis of the "Olympic Youth" festival]. AB - On the basis of the festival production "Olympic Youth", Berlin 1936, the author examines the structure of mass stagings in Hitler Germany, the fascination felt by the participants, and the psychologically formative effect underlying the relationship of "leader" to "mass". In this connection, he draws particular attention to the interplay of perfect discipline and unbridled eruption and to the suspension of reality in favor of illusion. PMID- 2200082 TI - [Evaluation of bone age in patients with kwashiorkor]. AB - The present work is the result of a multicentric study performed at Hoima and Kitgum Hospitals in Uganda on a group of 20 children with Kwashiorkor. Bone age was evaluated on the X-ray film of the children's left hand and wrist, according to Tanner and to De Roo, by 2 different evaluators. The final results were compared. Eighty-five % of the patients presented delayed bone maturation: such a result confirms the importance of malnutrition on skeletal development. The data reported by other authors are also discussed. PMID- 2200083 TI - [Value of echographic examination in the study of osteomyelitis]. AB - Beside conventional radiology and bone scintigraphy, an important role is played in the diagnosis of osteomyelitis by sonography (US). This technique is especially useful to detect fluid collections in the soft tissues adjacent to the bone. Ten patients with osteomyelitis were examined: in 8 cases the presence of fluid collections was demonstrated, which were sometimes spreading along the bone axis and sometimes localized in a single site. The collection was subperiosteal in all cases. Sonography proved thus useful in providing further information on the bone affected with osteomyelitis. PMID- 2200084 TI - [Echography of the hip of the newborn infant]. AB - The authors report on their experience with 2164 US exams of the hip performed over last year on newborns, according to Graf's technique. The babies were divided into 2 groups at first examination: risk/no risk. We considered as risk factors: a positive family history, malposition in utero, abnormalities at birth, and being one of twins. Hips 2a+ and 2a- according to Graf were grouped as "borderline hips" (BLH), extrapolating them from negative and positive cases. BLH have generally shown a tendency to spontaneous normalization, although worsening of the condition was observed in 7.9% of cases. A high incidence of positivity (5.1%) was observed in the no-risk group, versus 9% in the risk group. Moreover, there was low agreement between clinical examination and US findings: the need for US screening is therefore pointed out, not only to promptly detect a decentered hip, but also to prevent the development of juvenile coxarthrosis in case of dysplasia. Premature babies were also studied, and those underweight for their gestational age: the incidence of positive subjects in this group (4.5%) was not higher than that found in the no-risk group (5.1%). We report on the phases of hip normalization as related to stage and therapy. Graf's technique, besides being at present the only reproducible one, represents a method common to all radiologist which allows hip measuring and staging. PMID- 2200085 TI - [Ultrasonic identification of foreign bodies in superficial soft tissues]. AB - The authors investigated US capabilities in detecting foreign bodies retained in superficial soft tissues. Ten patients were studied: 5 of them with history of recent trauma and 5 with painful superficial swelling where US revealed the presence of foreign matter. US findings were confirmed by subsequent surgical specimens. In the first group of patients, a hyperechoic stripe was observed, whereas a hyperchoice nodule with a hyperechoic core was detected in the second group of patients. The latter US pattern may be explained by the presence of a reactive granuloma. US has shown to be very useful in diagnosing this kind of lesion, and it can thus be considered as the only reliable imaging modality to identify radiolucent foreign bodies. PMID- 2200086 TI - [Thermal dose and fractionation in clinical hyperthermia]. AB - Hyperthermia is one of the most promising methods for cancer treatment. Two important problems are nonetheless to be solved to define the actual role of this technique: the first one is how to express the thermal dose, and the second one is to assess the optimal sequence for the administration of heat and radiation. The authors critically reviewed the literature on the subject, pointing out those questions which have not yet been solved. Their work was then integrated with their own clinical experience on 191 lesions treated by hyperthermia alone or combined with radiotherapy. The impact is also analyzed of such prognostic factors as minimum intratumor temperature and total number of heating session on the final results. PMID- 2200087 TI - [Optimization of a dosimetric procedure in total body irradiation]. AB - The experimental dosimetry of 2 radiotherapy beams produced by a 60Co Picker unit and by a Siemens 4 MV unit, respectively, was analyzed to verify the use of tissue air ratio (TAR) and tissue maximum ratio (TMR) in the computerized planning of total body irradiation (TBI). The use of a small ionization chamber PRO5P Capintec in anthropometric phantoms allowed us to test a computed calculation procedure adopted to reduce both experimental uncertainties and time consumption. The experimental test on the computed procedure was also useful to identify the equivalent fields the patient's body had to be divided into for dosimetric planning. Such dosimetric specifications as average dose to the patient and degree of dose inhomogeneity are calculated when the thickness of compensator filters in perspex is optimized. Following the guidelines reported in ICRU 29, a dosimetric record is presented. In page 1 the target volume is described, in page 2 the provisional treatment planning, and in page 3 the actual treatment planning, checked with in vivo TLD measurements, and the dose specifications for TBI. PMID- 2200088 TI - [Ultrasonic diagnosis of duodenal diaphragm]. PMID- 2200089 TI - [Accuracy of quantitative, morphological and functional evaluation in cardiac MR]. PMID- 2200090 TI - [Morphology and staining of the false gingiva and stabilized polished surfaces in complete dentures 2]. PMID- 2200091 TI - [Fabrication and natural stratification of dental ceramics 1]. PMID- 2200092 TI - Effects of allopurinol on endotoxin-induced increase in serum xanthine oxidase in the horse. AB - Using a modified bovine milk enzyme kinetic assay, xanthine oxidase activity of serum collected from 34 adult, healthy horses of both sexes was determined. Enzyme activity varied from 0 to 126 mU litre-1 with a mean of 44.95 +/- 21.05 mU litre-1. The optimal pH and temperature for maximal activity were 7.8 and 28 degrees C, respectively. Freezing the serum for four days at -70 degrees C did not destroy the enzyme activity. Various doses (25, 50 and 75 micrograms kg-1, intraperitoneally) of endotoxin (lipopolysaccharide D1 Escherichia coli O26:B6) previously known to have caused moderate to severe systemic clinical signs of endotoxaemia in horses produced a significant dose related increase in serum xanthine oxidase activity. Pretreatment (12 hours) with allopurinol (5 and 50 mg kg-1, intravenously [corrected]) significantly reduced the rise in xanthine oxidase activity in endotoxin (50 micrograms kg-1, intraperitoneally) treated horses. The results of this study suggest that xanthine oxidase catalysed production of superoxide radicals may play a role in the pathogenesis of endotoxaemia and that allopurinol, an alternate substrate, should be further evaluated for its therapeutic potential in endotoxin related systemic diseases in horses. PMID- 2200093 TI - Autoagglutination and the specificity of the indirect fluorescent antibody test applied to the identification of Taylorella equigenitalis. AB - Because the first strains of Taylorella equigenitalis isolated in the Netherlands autoagglutinated, identification was difficult. The source of carbon dioxide to create a carbon dioxide atmosphere for incubation influenced the emulsifiability of these strains. Strains were emulsifiable when cultivated in a carbon dioxide incubator (7 per cent carbon dioxide in air), but were autoagglutinable when cultivated in a candle jar, or in a jar with a carbon dioxide system or anaerobic system without the palladium catalyst. When strains autoagglutinated, they were identified by the indirect fluorescent antibody test. Although strains of other bacterial species, in particular Pasteurella haemolytica, also showed fluorescence, which was partly caused by autofluorescence, the indirect fluorescent antibody test appeared to be a reliable additional test for identifying T equigenitalis. PMID- 2200094 TI - Corticosteroid receptors and renal 11 beta-hydroxysteroid dehydrogenase activity. PMID- 2200095 TI - Glucocorticoids and control of glomerular filtration rate. AB - Glucocorticoids given acutely or chronically at physiological/pharmacological doses increase GFR in both experimental animals and humans. Glomerular micropuncture studies have shown that in the normal rat kidney, glucocorticoids vasodilate both the preglomerular and efferent resistances and result in an increase in glomerular plasma flow, which is the sole factor responsible for the increase in GFR. However, the mechanism(s) initiating these alterations in the glomerular microcirculation remain obscure. The glucocorticoid-induced increase in GFR does not appear to be due to volume expansion or alteration in tubulo glomerular feedback activity. Chronic glucocorticoid administration has been shown to increase renal prostaglandin synthesis in some but not all species; however, a link between increased prostaglandin production and glucocorticoid induced increase in GFR has not been established. A number of studies have examined glucocorticoid-induced alterations in renal vascular reactivity to vasoconstrictor agonists and the data have been conflicting. The suggestion that glucocorticoid-stimulated ANP production evokes the increase in GFR is unlikely to be correct based on substantial differences in the glomerular hemodynamic changes seen with ANP or glucocorticoids. An interesting proposal that appears well worth exploring is that glucocorticoids may increase GFR through their effects on catabolism of proteins to increase production of amino acids. Amino acid infusion markedly elevates GFR and has a similar glomerular hemodynamic profile as that of glucocorticoids. By virtue of their action to increase GFR, glucocorticoids increase the rate of electrolyte and water delivery into the nephron. Therefore, glucocorticoid-induced alterations in electrolyte and water excretion may be secondary to an elevation in GFR, in addition to direct actions of glucocorticoids on the tubule. Also, by determining the hemodynamic state of the kidney, and hence, rate of fluid delivery through the nephron, glucocorticoids may influence the sensitivity of the nephron to regulatory influences. Glucocorticoids have their most profound effect (especially clinically) by modifying the immunological or cellular mechanisms responsible for glomerular injury. Less important is their ability to increase GFR. In view of some evidence that suggests increasing glomerular pressure accelerates the progression of established renal disease, some might speculate that glucocorticoids actually increase glomerular damage under certain conditions. PMID- 2200096 TI - Glucocorticoid control of ammoniagenesis in the proximal tubule. PMID- 2200097 TI - [Adaptation of composites to enamel: relation to the appearance of marginal staining]. AB - Marginal staining is the major cause of failure of composite resin restorations. The following reasons were incriminated: The nonrespect of the integrity of the cavity limits during cavity obturation, as for instance, when a simple bevel is made. The appearance of fractures or composite bond strength failures during polishing procedures. This phenomenon can be enhanced by the use of composite finishing knives (KOMET) and by overfilling the cavity. PMID- 2200098 TI - [Human remains at Roc de Sers]. AB - The fossils remains discovered in 1923 on the Roc de Sers site (Charente, France) are very much alike. Dating from the Magdalenian, their features are the following: small size, strong joints, average size skull, jutting brow ridges and well-developed chin. Following a study of the relations between the climate and the morphology, a composite picture of skull n degrees 1 a reconstruction of the landscape are presented. They are mainly meant to point out the limits of the credibility of such reconstructions. PMID- 2200099 TI - [Adhesion of artificial teeth to polymethacrylate resins]. AB - In this study the microleakage is first tested between the poly methylmethacrylate resins used in removable partial denture and the artificial teeth after storage in 100% humidity at 37 degrees C or after aging by an hydrothermal fatigue stress. Then the porcelain butt joint was improved by pyrolytic silanization. MATERIALS: A metallic flask was realized, in this study, to polymerize strictly identical samples. RESULTS: Due to polymerization in 100% humidity, the silane bond will be destroyed. Thermo-or chemopolymerizing resins are the only resins to allow the bonding with porcelain teeth by means of the sandwich technic. PMID- 2200100 TI - [Local antimicrobial treatments for periodontal disease]. PMID- 2200101 TI - [Doctor Albert Kyper, his anti-Cartesian speech on method (1643) and odontology]. AB - Young ambitious Lutheran, and then converted to Calvinism, Albert Kyper was opposed to Cartesianism, telling that "this was harmful towards Faculty of Medicine." He recognized decadent scolastic method and that it was just necessary to follow the ancients' ways. He wanted to ignore Fallope, Vesale, Eustache, Fernet, minor authors. PMID- 2200102 TI - [Behavior of a dental rotary instrument alloy after titanium nitride coating]. AB - A titanium nitride coating has been deposited on steel and tungsten carbide dental rotary instruments. This process is carried out under partial vacuum, by reacting vapourized metal (titanium) and nitrogen in a plasma. The instruments temperature is around 500 degrees C during coating. We have determined by micro analysis the treatment modifications upon the different bursa components. VICKERS microhardness tests have shown the coating temperature effects towards the heat treatments of employed steels. PMID- 2200103 TI - [Mechanism of tooth eruption: review of research and current theories]. PMID- 2200104 TI - Antigenic and dynamic properties of the surface of Onchocerca microfilariae. AB - We analyzed the antigenicity and stability of the surface of skin microfilariae (mf) of Onchocerca cervicalis, a horse parasite. These mf express antigens on their surface that are cross-reactive with the cattle parasite O. lienalis and with the human parasite O. volvulus. The surface of living O. cervicalis mf was radioiodinated using Iodogen and the labeled components were solubilized in buffers containing sodium dodecyl sulphate (SDS), or extracted with the milder detergent octyl-beta-D-glucopyranoside (OGP). Electrophoresis of this material showed seven prominent bands, one of which (14 kDa) was specifically precipitated by antisera from rabbits immunized with mf from either O. cervicalis, O. lienalis, or O. volvulus, and by human sera obtained from infected individuals in Chiapas, Mexico. Other components were precipitated by either the rabbit or the human sera. In addition, antisera from mice immunized with O. cervicalis mf bound specifically to the surface of freeze-thawed uterine O. lienalis and O. volvulus mf as detected by immunofluorescence. This fluorescence was lost from the surface of O. cervicalis mf in a temperature-dependent fashion. Live mf incubated on ice with mouse anti-mf antisera and secondary FITC-GAM, showed uniform surface fluorescence. When these mf were incubated at 37 degrees C, but not at 0 degrees C, the fluorescent pattern changed with time. First, small non-fluorescent patches arose, followed by an increasingly wide belt devoid of fluorescence, and finally, no visible fluorescence. These changes in the mf surface suggest potential mechanisms for immune evasion by filarial parasites. PMID- 2200105 TI - An economical procedure for screening of hybridoma supernatants for surface reactive antibodies to filarial larvae. AB - Third- and fourth-stage larvae of Onchocerca volvulus can be attached to the lids of 96-well microtiter plates to facilitate the screening of hybridoma supernatants reactive with filarial larvae. Plates are coated with a solution consisting of 0.1% gelatin, and 0.01% chrome alum. Following coating of plate lids one larva per depression is placed on the lid. An immunofluorescence assay (IFA) was conducted in which there were two 45 minute incubations and eight separate washes by immersion in PBS. At the completion of the assay over 90% of the larvae remain attached. The background in IFA is minimal and the results are consistent with those obtained using a suspension IFA. This technique permits rapid identification of antibody producing hybridomas with small numbers of larvae. PMID- 2200106 TI - The Nobel lectures in immunology. The Nobel Prize for Physiology or Medicine, 1930, awarded to Karl Landsteiner. 'In recognition of his discovery of human blood groups'. PMID- 2200107 TI - Interleukin 1 beta increases the cytosolic free sodium concentration in isolated rat islets of Langerhans. AB - Interleukin 1 (IL-1) exerts both stimulatory and inhibitory (cytotoxic) effects on insulin-producing beta cells in isolated pancreatic islets. Since alteration in ion fluxes is crucial for endocrine cell activation and is a denominator of cell death, and since IL-1 was recently shown to increase the total sodium content in a murine pre-B-lymphocyte cell line, we investigated the effect of recombinant human IL-1 beta (rhIL-1 beta) on the cytosolic free sodium concentration (fNa+i) in rat islets. Furthermore, long-term rhIL-1 beta effects on islet cell function were studied during exposure of islets to amiloride, a blocker of the plasma membrane Na+/H+ exchange. One hour of islet exposure to 60 U/ml of rhIL-1 beta caused a threefold increase in fNa+i in islet cells, and this effect was abolished by depletion of extracellular sodium. Blockade of Na+/H+ exchange with amiloride abolished the inhibitory effect of rhIL-1 beta on insulin release. In conclusion, rhIL-1 beta was found to increase sodium influx in pancreatic islet cells. This might underlie the widespread effects of rhIL-1 beta on beta-cell function and morphology, possibly related to IL-1-mediated toxic free radical formation. PMID- 2200108 TI - [Immunosuppressive therapy of multiple sclerosis using cyclosporin A and azathioprine. Long-term effects, risks, proton spin tomography and immunological findings]. PMID- 2200109 TI - [Echogenic splenic lesions--incidence and differential diagnosis]. AB - In order to estimate the incidence and clinical relevance of echogenic focal lesions in the spleen, 121,372 ultrasound investigations from seven laboratories were evaluated. Ninety-two cases with echogenic lesions in the spleen were reviewed (incidence: 3.2 to 14.2 of 10,000 patients). Differential diagnosis included neoplastic tumors (17.4%; five metastases, three lymphomas, seven hemangiomas, one lymphangiomatosis), vascular disorders (17.4%: bleeding, infarct) and inflammatory focal lesions (8.7%; abscess, calcifications). Follow up studies showed no change in size and pattern in a further 17.4% of the lesions, indicating benign disorders. Thirty patients suffered from a malignant condition with splenic metastasis or lymphomas in eight cases. In a further five patients, it was possible to confirm echogenic hemangiomas. There are no specific echographic patterns which differentiate hemangiomas from malignant tumors. PMID- 2200110 TI - [Ultrasound echogenic splenic tumors: nodular manifestation of type C Niemann Pick disease]. AB - A female patient is described with highly echogenic splenic nodes found in routine diagnosis. After CT and angiography a splenectomy was carried out. The histological finding of sea blue histiocytes and the extended family history suggested a subtype of Niemann-Pick disease. Biochemical lipid analysis of the spleen confirmed Type-C Niemann-Pick disease. Niemann-Pick disease and its subtypes are discussed briefly. PMID- 2200111 TI - [Pancreatitis-induced pseudocysts of the spleen: a rare complication]. AB - Secondary splenic cysts usually occur following blunt abdominal trauma. In rare cases, the spleen can be affected in pancreatitis. Since the clinical findings are fairly uncharacteristic, this was a difficult diagnosis to make before imaging examination techniques became available. These cysts only became apparent as a result of their complications. Today, thanks to sonography and abdominal CT scan, these cysts can be detected in their asymptomatic stage. Furthermore, interventional sonography allows the puncture and drainage of these cysts, and this technique is thus an alternative to surgery. Two cases of pancreatitis with splenic involvement are presented. PMID- 2200112 TI - [Diagnosis of tumors of the large intestine by colonic ultrasound]. AB - Retrograde instillation of liquid into the colon allows a specific, percutaneous sonographic examination of the colon to be performed. As part of a prospective study of the diagnosis of colonic tumors in 260 patients, this form of colon sonography was examined together with colonoscopy. Sonographically, colonic polyps and carcinomas of the colon manifested as echogenic, parietal masses. Using colonic sonography, it was possible to identify 96% of the carcinomas that had been diagnosed colonoscopically. The sonographic diagnosis of polyps was insufficient if they were smaller than 6 mm: if they were larger than 7 mm, however, diagnostic sensitivity was 91%. The results of this study show that colon sonography is a new, sensitive method in the diagnosis of colonic tumors. PMID- 2200113 TI - [Ultrasound diagnosis of clinically atypical invagination in the child]. AB - Report on sonographic diagnosis of clinically atypical ileocolic invagination in a four-year old boy. Desinvagination by an enema with water-soluble contrast material was not successful. Surgery resulted in the surprising additional finding of an acute appendicitis which might have been the reason for the invagination. PMID- 2200114 TI - [Ultrasound evaluation of gallbladder function using planimetry]. AB - Fourteen patients with gallstones (13 female, 1 male; mean age 45.1 +/- 14.6 years; mean body weight 105.7% +/- 18.7% of ideal body weight) were included in the present study. Prior to and 45 min. after administration of a standard fatty meal, patients were examined by ultrasound. The mean gallbladder volume decreased from 20.94 +/- 10.0 cm3 to 6.83 +/- 3.5 cm3 (ejection fraction (EF) = 61.7 +/- 27.9%), the mean cross-sectional area from 12.0 +/- 3.4 cm2 to 6.0 +/- 2.8 cm2 (percentage changes 48.0% +/- 25.5%). A correlation is shown to exist between the ejection fraction of gallbladder emptying and the decrease of gallbladder area (r = 0.91; p less than 0.001). The simple measurement of the gallbladder area of a section through the long axis adequately demonstrates gallbladder contraction. PMID- 2200115 TI - [Ultrasound image of an unusual intrahepatic site of a bile duct cyst]. AB - An intrahepatic cyst was found ventral and cranial to the gallbladder without choliangectasy in an infant of 8 months of age. Final diagnosis of a bile duct cyst was arrived at intraoperatively. The article discusses the possible aetiology, non-invasive diagnosis and sonographic differential diagnosis. Sonography is discussed as the method of choice in assessing intrahepatic and extrahepatic cysts and the bile ducts. PMID- 2200116 TI - [Multiple amebic liver abscesses: ultrasound diagnosis and ultrasound-controlled puncture]. AB - Amebic colitis and amebic liver abscess were diagnosed in a 45-year-old patient who had returned from Thailand. Ultrasound scans performed after starting treatment with metronidazole showed an abscess located above the right kidney that had enlarged to a maximum diameter of 9.7 cm. Since rupture of this lesion was felt to be imminent, ultrasound-guided needle biopsy was performed and 300 ml of abscess fluid evacuated. The patient experienced rapid relief of his symptoms. The role of ultrasound imaging in the diagnosis and follow-up of amebic liver abscesses and the indications for ultrasound-guided needle aspiration are discussed. PMID- 2200117 TI - [Dynamic contrast medium-aided ultrasound cavography in patients with a caval filter]. AB - In 35 patients during 42 examinations, vena-caval blood flow was visualized by application of a new ultrasonic contrast medium (Echovist) via a dorsopedal vein. A caval filter had previously been implanted in 32 patients. In 94 out of 99 cases, application of the contrast medium allowed a diagnostically relevant enhancement of the echogenicity of the caval blood flow. In addition, the caval filters allowed altered flow geometry to be depicted in detail. PMID- 2200119 TI - Oregon's plan comes to the capital. PMID- 2200118 TI - [Ultrasound cystometry with reference to urinary bladder form and bladder filling]. AB - In 103 patients we performed sonographic determination of the volume (V) of the urinary bladder, being the product of the transversal (q), ventrodorsal (t) and craniocaudal (h) diameters, and compared this with the excreted volumes of urine. Depending on the shape and filling of the bladder we found different correlations from which it was possible to calculate three correction factors (F) for the formula V = (q x t x h) x F:F = 1.25 for volumes less than 150 ml; F = 0.9 for spherically sagittal section and volumes greater than 150 ml. The factor 0.5 given in most textbooks on sonography will in the majority of cases result in underestimating the urinary bladder volumes. Accurate sonocystometry taking the shape and filling into consideration is imperative for performing follow-up and treatment monitoring in neurogenic disturbances of voiding of the bladder or occlusive disturbances of flow in the region of the urethra. PMID- 2200120 TI - Telomeres and their synthesis. PMID- 2200121 TI - Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. AB - High-affinity nucleic acid ligands for a protein were isolated by a procedure that depends on alternate cycles of ligand selection from pools of variant sequences and amplification of the bound species. Multiple rounds exponentially enrich the population for the highest affinity species that can be clonally isolated and characterized. In particular one eight-base region of an RNA that interacts with the T4 DNA polymerase was chosen and randomized. Two different sequences were selected by this procedure from the calculated pool of 65,536 species. One is the wild-type sequence found in the bacteriophage mRNA; one is varied from wild type at four positions. The binding constants of these two RNA's to T4 DNA polymerase are equivalent. These protocols with minimal modification can yield high-affinity ligands for any protein that binds nucleic acids as part of its function; high-affinity ligands could conceivably be developed for any target molecule. PMID- 2200123 TI - Regulation of activity of a transcriptional anti-terminator in E. coli by phosphorylation in vivo. AB - Expression of the bgl operon of Escherichia coli is regulated in vitro by phosphorylation and dephosphorylation of a positive regulatory protein, BglG, which functions in its nonphosphorylated state as a transcriptional antiterminator. The degree of phosphorylation of BglG in vivo was shown to be dependent on the cellular levels of BglF protein, which is both the BglG kinase and phosphatase. The degree of phosphorylation of BglG also depended on the presence or absence of a beta-glucoside, the inducer of operon expression. Addition of inducer to cells in growth medium resulted in rapid dephosphorylation of phosphorylated BglG. The bgl operon is thus regulated by a sensory system that modulates gene expression by protein phosphorylation and dephosphorylation in response to the external levels of inducer. PMID- 2200122 TI - Design, activity, and 2.8 A crystal structure of a C2 symmetric inhibitor complexed to HIV-1 protease. AB - A two-fold (C2) symmetric inhibitor of the protease of human immunodeficiency virus type-1 (HIV-1) has been designed on the basis of the three-dimensional symmetry of the enzyme active site. The symmetric molecule inhibited both protease activity and acute HIV-1 infection in vitro, was at least 10,000-fold more potent against HIV-1 protease than against related enzymes, and appeared to be stable to degradative enzymes. The 2.8 angstrom crystal structure of the inhibitor-enzyme complex demonstrated that the inhibitor binds to the enzyme in a highly symmetric fashion. PMID- 2200124 TI - Antibody-mediated activation of Drosophila heat shock factor in vitro. AB - Eukaryotic cells respond to elevated temperatures by rapidly activating the expression of heat shock genes. Central to this activation is heat shock inducible binding of the transcriptional activator, termed heat shock factor (HSF), to common regulatory elements, which are located upstream of all heat shock genes. The DNA binding activity of the inactive form of Drosophila HSF was induced in vitro by treatment with polyclonal antibodies to the purified, in vivo activated factor. This finding, together with observations that high temperature and low pH activate HSF binding in vitro, suggests that the inactive form of HSF can directly recognize and transduce the heat shock signal without undergoing a covalent modification of protein structure. PMID- 2200125 TI - Specific tropism of HIV-1 for microglial cells in primary human brain cultures. AB - Human immunodeficiency virus (HIV) frequently causes neurological dysfunction and is abundantly expressed in the central nervous system (CNS) of acquired immunodeficiency syndrome (AIDS) patients with HIV encephalitis or myelopathy. The virus is found mostly in cells of the monocyte-macrophage lineage within the CNS, but the possibility of infection of other glial cells has been raised. Therefore, the effects of different HIV-1 and HIV-2 strains were studied in primary cultures of adult human brain containing microglial cells, the resident CNS macrophages, and astrocytes. These cultures could be productively infected with macrophage-adapted HIV-1 isolates but not with T lymphocyte-adapted HIV-1 isolates or two HIV-2 isolates. As determined with a triple-label procedure, primary astrocytes did not express HIV gag antigens and remained normal throughout the 3-week course of infection. In contrast, virus replicated in neighboring microglial cells, often leading to their cell fusion and death. The death of microglial cells, which normally serve immune functions in the CNS, may be a key factor in the pathogenesis of AIDS encephalitis or myelopathy. PMID- 2200126 TI - Toxoplasma gondii: fusion competence of parasitophorous vacuoles in Fc receptor transfected fibroblasts. AB - After actively entering its host cells, the protozoan parasite Toxoplasma gondii resides in an intracellular vacuole that is completely unable to fuse with other endocytic or biosynthetic organelles. The fusion blocking requires entry of viable organisms but is irreversible: fusion competence of the vacuole is not restored if the parasite is killed after entry. The fusion block can be overcome, however, by altering the parasite's route of entry. Thus, phagocytosis of viable antibody-coated T. gondii by Chinese hamster ovary cells transfected with macrophage-lymphocyte Fc receptors results in the formation of vacuoles that are capable of both fusion and acidification. Phagocytosis and fusion appear to involve a domain of the Fc receptor cytoplasmic tail distinct from that required for localization at clathrin-coated pits. These results suggest that the mechanism of fusion inhibition is likely to reflect a modification of the vacuole membrane at the time of its formation, as opposed to the secretion of a soluble inhibitor by the parasite. PMID- 2200127 TI - [Clinical management of lesions of the rotator cuff]. AB - Lesions of the rotator cuff are caused in most cases by degenerative changes in the critical area around the tuberosities of the humerus. Clinical examination reveals atrophy of the supra- and infraspinatus muscles, a painful arc of movement and, especially, pain at night. There are many clinical tests that can be helpful in the diagnosis. Both ultrasonography and arthrography have proved to be very sensitive methods for the detection of rotator cuff tears. Ultrasonography allows determination of the size and location in addition. Conservative treatment includes rest, physical therapy and anti-inflammatory medication. In many cases the symptoms are improved by many weeks of conservative treatment alone. Operative treatment becomes necessary when no pain relief and no satisfactory movement can be achieved. Complete correction of the tendon defect is important for postoperative care. Passive exercise must allow the tendon repair to remain intact without subjecting it to undue stress. PMID- 2200128 TI - [Sonographic imaging of meniscus lesions. An experimental study]. AB - There is still no general agreement on the value of ultrasonographic visualization of pathologic changes in the knee menisci. Some examiners report on large patient collectives in which it has yielded accurate diagnoses in 90% of cases. Other authors describe much higher failure rates and unreliable imaging of meniscal lesions. The aim of this experimental study was to determine how reliable the imaging of such lesions is, which of the different types can be recognized, and what their ultrasonic morphological characteristics are. To this end, the examinations were performed on isolated menisci in a waterbath to avoid artefacts that might be caused by the tissues surrounding the meniscus in situ. It was shown that all types of lesion except the transverse rupture could be visualized and localized reliably. The different types of meniscal injuries all produce the same sort of appearance on the screen: a hard, glaring reflection of sound waves. The necessity of using a 7.5-MHz sector, or curved-array transducer for the examination is emphasized. PMID- 2200129 TI - [Poly-, multiple trauma and intra-abdominal injuries]. AB - The present work deals with the problem of abdominal injuries in polytraumatized patients. The results were obtained from a retrospective study of the records of 530 polytraumatized patients treated at the Central Hospital of the German Federal Armed Forces (Bundeswehr). In all, 193 of these patients had abdominal injuries. The overall mortality was 23.8% (n = 126): mortality among the patients with abdominal injuries was 26% (n = 50). Abdominal injuries alone led to death in 9.1% (n = 1), but mortality increased to 18.4% when at least one extra abdominal injuries was also present. A combination of abdominal injuries and two or more extra-abdominal lesion led to a mortality rate of 27%. Mortality was found to be age- and sex-related: in young children and patients over 55 years (especially those around 70) mortality was 33.3%-72%. Among the cases with fatal outcome there was a female-to-male ratio of 3:2. The most common causes of death were: hemorrhage shock (62.3%), head injuries (37.7%), septicemia (8.1%), pneumonia, and ARDS (5.4% each). Within the last eight years we have used the following supplementary examination methods: computed tomography, peritoneal lavage, and ultrasonography. The retrospective study has shown that CT is not the examination of choice. The reliability with lavage and ultrasonography was approximately the same, but lavage was found to be more dangerous. Therefore, we abandoned lavage and used sonography only. However, we are of the opinion that any surgeon should use the examination method that has yielded the best results for him or her, to ensure the best possible outcome for the patient. PMID- 2200130 TI - Mechanisms of drug resistance in breast cancer. AB - Drug resistance is one of the most important problems in the treatment of cancer. Patients become resistant not only to the drugs used initially, but also those to which they have not yet been exposed. A number of factors influence the therapeutic outcome of patients with breast cancer, foremost of which is the tumor burden. The greater the tumor burden, the more difficult it is to achieve an adequate and lasting response. Timing of treatment, dose and schedule of therapy, and the duration of therapy are also important considerations in the therapeutic outcome. Of primary importance is the development of drug resistance, which appears to be related to genetic alterations that result in altered cellular pharmacology and lead to reduced drug efficacy. Multiple mechanisms may be involved, all or any number of which may occur simultaneously within each cell, producing an overall drug-resistant phenotype. PMID- 2200131 TI - Basic principles in the use of adjuvant therapy. AB - Data from collaborative trials clearly indicate that the primary effect of adjuvant therapy is to delay death from breast cancer by months or years. However, adjuvant chemotherapy does not appear to prolong the survival of women aged 50 years or older, and tamoxifen has not yet been shown to improve the survival of women younger than age 50. In three trials involving node-negative patients, all showed a highly significant improvement in disease-free survival despite different chemotherapeutic regimens and durations of regimens. PMID- 2200132 TI - Salvage therapy for metastatic disease. AB - Available evidence supports the use of the combination of mitomycin plus vinblastine as salvage therapy for metastatic breast cancer. In our experience with 39 patients, this combination is as at least as effective as doxorubicin salvage therapy. In addition, those who respond usually do so within the first 4 weeks of treatment. Trial results show that its safety and toxicity profile was more favorable than doxorubicin-based regimens. In addition, the hematologic toxicities associated with mitomycin can be managed by decreasing the dose and/or prolonging the dosing interval. Most of the patients in this study received full doses of chemotherapy for the duration of the trial. We concluded that mitomycin plus vinblastine is effective and well tolerated in the treatment of metastatic breast disease. PMID- 2200133 TI - Clinical pharmacology of carboplatin. AB - Experimental and clinical data indicate that carboplatin is as effective as cisplatin in the treatment of ovarian cancer patients with advanced bulky disease. It has an improved toxicity profile with a low incidence of ototoxicity, neuropathy, and nephropathy. In the absence of severe myelosuppression, the dose of carboplatin should be escalated in patients who have good renal function. Over the next few years, carboplatin will either replace cisplatin, or will be easier to use in a dose-intensive fashion. PMID- 2200134 TI - Diagnosis at the bedside by gene analysis. AB - Four different ideas are important in understanding the diagnostic applications of DNA analysis. When DNA changes in a gene are detected, one must determine whether they represent DNA polymorphisms (changes not associated with disease) or mutations that affect expression of the gene. Differences seen in mutations in different patients (heterogeneity) often explain clinical variation at a molecular level. Current methods used for gene analysis include restriction enzyme analysis, polymerase chain reaction amplification, allele-specific oligonucleotides, denaturing gradient gels, and DNA sequence analysis. Gene diagnosis is applicable to many clinical disorders, both genetic and acquired. Requisites are a portion of the gene involved or a segment of DNA that lies close to the gene. PMID- 2200135 TI - Microangiopathic hemolytic anemia as the initial manifestation of porcine valve failure. AB - We compare the findings in a patient whose microangiopathic hemolytic anemia was the initial sign of porcine valvular dysfunction, with those of six other patients with porcine valve failure seen at Tripler Army Medical Center and with those of 12 patients with hemolytic anemia and porcine valve failure whose cases have been reported in the literature. Total bilirubin and serum lactic dehydrogenase were directly related to the degree of anemia in patients with porcine valve dysfunction. Echocardiography confirmed valve dysfunction in only four of eight patients, while cardiac catheterization confirmed valve failure in 16 of 17 patients. Laboratory evidence for hemolysis was minimal in 31 patients who had normal, functioning porcine valves. Microangiopathic hemolytic anemia in the presence of a porcine prosthetic heart valve, and in the absence of other causes, warrants a thorough evaluation to rule out valve dysfunction. Routine laboratory screening for hemolysis may aid the early diagnosis of porcine valve failure. PMID- 2200136 TI - Pancreaticoduodenal artery aneurysms: changing patterns. AB - A true pancreaticoduodenal artery (PDA) aneurysm (ie, one not associated with pancreatitis) is the second least common splanchnic artery aneurysm; it is usually situated in or near an area that is hard to dissect, and it has a distinct propensity to rupture. We reviewed a total of 36 cases of PDA aneurysm, including three from our institution, and we analyzed them in two time periods with relation to age, sex, method of diagnosis, morbidity, and mortality. Cases reported before 1970 were compared with those reported during or after 1970. The male-female ratio was 4:1 before 1970 and 1:1 after 1970, yet the mean age has stayed significantly lower for female populations (P less than .02). The use of angiography has increased significantly recently (P = .004). The overall mortality has not improved significantly (P = .08); however, if the initial diagnosis was made by angiography, the survival was significantly better (P less than .025). Surgical intervention remains the standard treatment, but preoperative angiography significantly improves operative results. Anecdotal reports suggest that selected high-risk cases may be successfully managed by therapeutic angiography with embolization. PMID- 2200137 TI - Tracheal agenesis. AB - Tracheal agenesis is a rare congenital anomaly. We report a case and review the cases previously reported. Clinical features that might indicate tracheal agenesis include antenatal polyhydramnios, severe respiratory distress, absence of an audible cry, failure to advance an endotracheal tube beyond the larynx, a palpable distal trachea, clinical improvement after esophageal intubation, and roentgenographic absence of a tracheal air column with an abnormal position of the carina. For immediate management of the affected infant, we recommend intubation of the esophagus with an endotracheal tube to provide an air passage, and determination of the level of the defect by careful use of contrast material and roentgenography. Infants having type I tracheal agenesis may benefit from immediate tracheostomy. PMID- 2200138 TI - Cocaine in the cradle: a hidden epidemic. AB - Intrauterine exposure to cocaine is reaching epidemic proportions and is affecting the lives of an increasing number of infants and children. The toxic effects are manifested as microcephaly, growth retardation, brain infarcts, congenital malformations, and withdrawal symptoms lasting for several weeks. Preliminary long-term follow-up studies reveal worrisome psychologic alterations that may profoundly affect the personality of exposed individuals. PMID- 2200139 TI - Bronchoscopy-induced fatal asystole in tetanus: the result of combined carotid body chemoreceptor and vasovagal reflexes. AB - A 44-year-old man with tetanus had bradycardia with hypotension and then died suddenly when asystole developed during bronchoscopy. Although signs and symptoms of sympathetic hyperactivity are characteristic of tetanus, vagal stimulation via vasovagal and carotid-body chemoreceptor reflexes may produce sudden, unexpected, and catastrophic effects. PMID- 2200140 TI - Endocarditis and hip arthritis associated with Scedosporium inflatum. AB - A 30-year-old man had endocarditis and hip arthritis associated with the recently recognized fungus, Scedosporium inflatum. Inhibition, and possibly cure, of endocarditis occurred with medical therapy alone. Data from in vitro susceptibility testing did not predict clinical response. This case also illustrates the need to standardize fungal susceptibility testing and to remain vigilant for emerging pathogens. PMID- 2200141 TI - Ophthalmomyiasis interna lentis. AB - An examination in 1981 of a 62-year-old white woman, who had had decreased vision in the right eye since she was 11 years old, revealed the typical retinal findings of ophthalmomyiasis. The larval exoskeleton was found imbedded temporally in the lens. On reexamination in 1989 no change was found. PMID- 2200142 TI - Current trends in the diagnosis and treatment of hepatic artery aneurysms. AB - Aneurysms of the hepatic artery are rare lesions that constitute 20% of all splanchnic artery aneurysms. Their well-documented natural history includes progressive enlargement and eventual rupture. Computerized tomography, abdominal ultrasonography, or MRI may be used for initial evaluation, but angiography is required to make the definitive diagnosis and for delineation of the vascular anatomy. The lesion should be corrected surgically after the diagnosis is confirmed. Lesions proximal to the gastroduodenal artery may be ligated if there is sufficient collateral flow to the liver. For lesions distal to this artery, surgical resection and reconstruction is required. Selective embolization of intrahepatic or subhepatic aneurysms may be an effective alternative in high-risk patients. We had two cases of aneurysm of the hepatic artery diagnosed at our institution over the course of 18 months. Excellent results were obtained from surgical revascularization of the liver in both cases. PMID- 2200143 TI - Complementary use of Doppler sonography and delayed right lateral scintigraphy for the diagnosis of choledochal cysts. AB - Both sonography and hepatobiliary scintigraphy can help to demonstrate a choledochal cyst. Our case further demonstrates that Doppler sonography and right lateral or oblique scintigraphic views can be used to differentiate more completely this entity from other infantile cholestatic syndromes. These additional maneuvers may be particularly advantageous in the affected infant under a year old in whom a confusing clinical picture may obscure the correct diagnosis. PMID- 2200145 TI - Oxyphilic (Hurthle cell) adenoma arising in a black thyroid gland. AB - We report this case to further document in the literature morphologic changes encountered in a black thyroid gland. It is only through an expanding data base that future conclusions may be reached regarding the role, if any, of minocycline in some of these alterations. PMID- 2200144 TI - Rheumatoid pleuritis. AB - My case is one in which the principal manifestation of rheumatoid arthritis is pleurisy. It is a case that underscores the clinical nuances of rheumatoid pleuritis. The major articles that have shaped our view of rheumatoid pleuritis are discussed in light of my case, a perspective that raises the possibility that some of the established biases about rheumatoid pleuritis may be misleading. It is necessary to consider rheumatoid pleuritis in any patient with an unexplained pleural effusion. PMID- 2200146 TI - Patterns of failure in the original Besser bipolar prosthesis. AB - Fourteen original Besser endoprostheses inserted in young patients with osteonecrosis of the femoral head were reviewed. Two cups dislocated early and 1 other required replacement due to acetabular degeneration. Component disassembly occurred in 4 hips, which had exhibited persistently vertical cups. Their stems revealed notching medially and the cups showed gross erosion and failure. The remaining 5 hips were mobile and pain free, but in 3 of these the cups exhibited a persistently vertical orientation and, as such, are predisposed to failure. Only one article reporting early good results using this prosthesis has been published. The failure rate of 50% in this series is disappointing. PMID- 2200147 TI - Mechanisms and management of heart failure in active rheumatic carditis. AB - Fulminating active rheumatic carditis has been observed for over three decades in this environment with no recent alteration in either the incidence or the pattern of presentation. Heart failure (in this context defined as 'an inadequate circulation at rest together with a raised pulmonary venous pressure, with or without an associated high systemic venous pressure in the absence of haemodynamically significant tricuspid valve disease or pericardial effusion') is prevalent but occurs only when a haemodynamically important left-sided valve lesion supervenes. Regurgitation is the predominant valve lesion and involves principally the mitral valve. Mitral annular dilatation is marked and predisposes to lengthening--or rupture--of chordae tendineae and prolapse of the anterior leaflet. The resultant cardiac work-overload apparently perpetuates or aggravates the rheumatic activity. Heart failure, as defined, whether caused by or associated with active rheumatic carditis, makes surgical management of the valve lesion mandatory as a life-saving measure. Aggressive medical therapy for heart failure, which should include vasodilator drugs and especially angiotensin converting enzyme inhibitors, provides temporary improvement only. Contrary to ongoing doctrine, treatment with steroid drugs in this context is neither life saving nor beneficial. PMID- 2200148 TI - Ten-year observation of peptic ulceration at Ga-Rankuwa Hospital, Pretoria--1979 1988. AB - For the 10-year period 1979-1988, the incidence of endoscopically diagnosed peptic ulceration at Ga-Rankuwa Hospital was studied with particular reference to: type of ulcer; age, sex and place of residence of the patients; and patient's occupations. The incidence of peptic ulceration remained unchanged. In this area, gastric ulceration is a rare disease among black people. Early urbanisation had no influence on incidence but more patients from developing rural areas were seen as the study progressed. There was a peak incidence during August. PMID- 2200149 TI - [Recurrent acute polyhydramnios treated with indomethacin]. AB - A case of recurrent acute polyhydramnios successfully treated with indomethacin is described. The possible mode of action and risks associated with the use of the drug are discussed. PMID- 2200150 TI - A reappraisal of prophylactic mastectomy. AB - The concept of prophylactic mastectomy was nurtured in the shadow of the radical mastectomy. It evolved as preferable to the mutilation caused by the procedure. It developed during a time when the difference between benignancy and malignancy was not as clear and when patients with benign disease were thought to be at significant risk. The idea of surgical prophylaxis accompanied by a superior cosmetic result, in comparison to the radical mastectomy is a noble one. In retrospect, however, it is clear that the indications were ill defined, based often on unfounded risk and predicated on patient and physician anxiety. The scope of risk in carcinoma of the breast has been narrowed, with new information identifying only specific subsets of women with proliferative types of benign disease as more susceptible to the subsequent development of carcinoma. Extensive reviews of material taken at biopsy that had been validated longitudinally have provided data to substantiate this contention. The concept of familial high risk must take into account the number of affected family members, at age diagnosis, menopausal status and bilaterality. The majority of indicants that motivated and propitiated the performance of the bulk of prophylactic mastectomies have lost their relevance. Prophylactic mastectomy for carcinoma, therefore, can perhaps be reserved for women with biopsy-proved, high-risk lesions or an exceptional familial risk, or both, or hereditary risk. Such women must choose for themselves and accept the uncertainty of hypothetic risk reduction, life-long continued surveillance and an altered body image. Guiding patients in the decision should involve a multidisciplinary team composed of a surgical oncologist, geneticist, pathologist, psychotherapist and plastic surgeon. As a concept, the reduction of risk is appealing, but remains yet to prove itself superior to rigorous clinical surveillance with high-quality mammography. The experience reflected in the literature of a seemingly low rate of subsequent carcinoma cannot be judged, because it seems that operations were applied indiscriminantly to patients selected by unknown means and from an unknown population pool. Success based on protecting those not at increased risk only invalidates the operation further. Most surgical and medical oncologists recognize that carcinoma of the breast is either localized or disseminated at the time of the initial diagnosis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2200151 TI - [The monitoring of gynecological radiotherapy using serial tumor marker determinations]. AB - In 149 collum and 45 corpus carcinomas tumor marker concentrations in serum have been measured before, during and sex to eight weeks after termination of radiotherapy. For the collum carcinomas (average of FIGO I to IV) the sensitivity of CEA was found to be 51%, SCC 67%, CEA +SCC 80%. In corpus carcinomas CEA had low sensitivity and could not readily be used for therapy monitoring. However, in a number of cases CA125 was a good substitute. Six to eight weeks after termination of radiotherapy the average tumor marker levels have been declined by comparison with the pretherapeutic values (100%): For the collum carcinoma CEA dropped to 39%, SCC to 57%; for the corpus carcinoma CEA to 72%, CA 125 to 81%. The highest diagnostic information was gained by comparison of post-therapeutical tumor-marker levels with cut off values obtained from healthy women of the same age group. After treatment in 29 of 106 collum carcinomas CEA and or SCC levels did still exceed these cut off values. In eleven cases this marker elevation was due to paraaortic lymph node metastases, in seven cases a local tumor residue was discovered and in six cases general metastases. In corpus carcinomas the main reason for post-therapeutic elevated CA125 values also were paraaortic lymph node metastases. Thus, the use of serial tumor marker determination for control of gynecological radiotherapy is a helpful tool in early detecting local tumor residues and metastases. The decision making for further radiotherapeutical measures will be much easier, if accompanying tumor marker determinations have been done during primary radiotherapy. PMID- 2200152 TI - [Sensitivity and specificity of CEA, Ca 15-3 and MCA levels in visceral breast carcinoma metastasis]. AB - The determination of mucin like carcinoma associated antigen (MCA) showed a sensitivity of 72% in visceral metastasis of breast cancer, of 25% in metastasis of stomach cancer and of 10.3% in metastasis of colorectal cancer. The sensitivity of CA 15-3 was 83% (n.s.) in metastasis of breast cancer, that of CEA was 29% (p less than 0.05). The sensitivity of isolated metastasis and isolated invasion of the lymph nodes was under 20% for MCA, CA 15-3 and CEA. PMID- 2200153 TI - Reversal of diabetic somatic neuropathy by whole-pancreas transplantation. AB - To answer the crucial question regarding reversibility of diabetic somatic neuropathy by whole-pancreas transplantation, metabolic studies and electron microscopic morphometry of the sciatic and testicular nerves were performed monthly for 2 years in three groups of highly inbred rats: (1) NC, 47 nondiabetic controls; (2) DC, 90 untreated alloxan-induced diabetic controls; and (3) DT, 230 diabetic rats given syngeneic pancreaticoduodenal transplants 6, 9, 12, 15, 18, and 21 months after induction of diabetes mellitus (DM). Six diabetic nerve lesions were quantitated by a "blind" protocol: (1) loss of myelinated axons, (2) intraaxonal glycogen deposits, (3) axons with glycogen deposits, (4) demyelinated axons, (5) degenerating axons, and (6) loss of intact axoglial junctions in paranodal terminal myelin loops. In the DT group, testicular nerve specimens were obtained just before transplantation and at death so that each animal served as its own control. As we have observed previously in untreated diabetic controls, all six nerve lesions progressed relentlessly for 2 years, in contrast to nondiabetic controls (p less than 0.01). Whole-pancreas transplants produced complete metabolic control of DM for life and reversed all six lesions in both sciatic and testicular nerves, even when done late in the course of DM. There was complete reversal of the nerve lesions when pancreatic transplantation was done within 15 months of the onset of DM. These results provide the first demonstration of reversal of diabetic somatic neuropathy by any form of DM therapy and extend our previous work in which whole-pancreas transplants were found to prevent both diabetic neuropathy and nephropathy and reverse mesangial enlargement in the kidney. PMID- 2200154 TI - Trophic stimulation of the ductal/islet cell axis: a new approach to the treatment of diabetes. AB - The purpose of this study was to demonstrate that the pancreas of the hamster contains a growth factor(s) that can induce cells associated with the ductular epithelium to differentiate along an endocrine pathway and thereby provide a means of regenerating a functioning islet cell mass. We have shown previously that partial obstruction of the pancreatic duct leads to the induction of nesidioblastosis. A cytosol extract prepared from the partially obstructed hamster pancreas was injected at a dose of 4000 microliters intraperitoneally twice a day for 2 days and produced significant increases in pancreatic weight, protein, and deoxyribonucleic acid of 18%, 18% and 42% respectively, over saline treated control animals. To assess the effects of this extract on morphology, 150 microliters intraperitoneally twice a day was administered for 21 days. Tissue was processed for histologic, morphometric, and autoradiographic analysis. Budding of endocrine cells from cells of the terminal ductules was observed in cytosol-injected animals and the number of islets per square millimeter was determined to be increased by 100% compared with saline-treated controls (p less than 0.01). Tritiated thymidine uptake by ductal and islet cells was increased tenfold and sixfold, respectively, over that of control animals (p less than 0.01). Cytosol extract was also administered to hamsters rendered diabetic by streptozocin. Survival in these animals was 100% compared with only 60% for saline-treated control animals (p less than 0.05). Furthermore, the blood levels of glucose in cytosol-treated animals was significantly less than the levels in saline-treated controls (p less than 0.05). We conclude that the pancreas does indeed contain a growth factor(s) responsible for the induction of nesidioblastosis and the new islet tissue is functionally capable of stabilizing a diabetic state. PMID- 2200155 TI - Enhanced production of endothelium-derived contracting factor by endothelial cells subjected to pulsatile stretch. AB - The purpose of this study was to assess the role of cyclic deformation in modulating the production by endothelial cells (ECs) in culture of a recently described endothelium-derived smooth muscle cell contracting factor, endothelin. We grew bovine aortic ECs to confluence on culture plates with flexible membrane bottoms. Vacuum (-20 kPa) was applied to deform the membrane to 24% strain at 60 cycles/min for 1, 3, or 5 days. Control ECs were grown on the same membrane but without vacuum deformation. The conditioned media were collected, centrifuged at 10,000 rpm for 10 minutes to remove cells and debris, and the supernatant fluid was subjected to radioimmunoassay for endothelin. The results demonstrate that bovine aortic ECs release a basal level of endothelin under stationary conditions (107.1 +/- 14.7 pg/10(5) cells), and this production increased fivefold to sixfold with cyclic stretch. Thus physical forces exerted on ECs in culture can influence the secretion of this vasoconstrictive molecule. PMID- 2200156 TI - Detection of surgical pathogens by in vitro DNA amplification. Part I. Rapid identification of Candida albicans by in vitro amplification of a fungus-specific gene. AB - The management of candidemia and disseminated candidiasis depends on rapid, unambiguous identification of Candida. Such identification is retarded by the slow growth of Candida from clinical specimens. Administration of effective but potentially toxic antifungal therapy is often withheld pending identification. To circumvent this slow growth and thus to expedite diagnosis and therapy, the polymerase chain reaction (PCR) was used to amplify a segment of fungal DNA coding for the cytochrome P450L1A1 (lanosterol-14 alpha-demethylase) in vitro. The technique provides unambiguous evidence of C. albicans in as few as 6 hours with a detection threshold of 10 organisms in a 100 mu specimen. Clinical specimens of urine (n = 4), sputum (n = 6), wound fluid (n = 1, and blood (n = 2) were collected from patients, and C. albicans was conventionally documented at these sites; in each case, PCR was confirmed. Of 17 additional specimens that were culture negative, PCR suggested the presence of yeast in two of the specimens. PCR-based detection of surgical pathogens may have broad application in rapid screening for the presence of organisms either indigenous to a particular surgical intensive care unit or peculiar to selected patient populations. PMID- 2200157 TI - Obstructive jaundice and renal failure in the rat: the role of renal prostaglandins and the renin-angiotensin system. AB - We have previously noted that bile duct ligation (BDL) in the rat results in decreased creatinine clearance (Ccr) and decreased urinary sodium excretion (UNaV) as well as increased renal prostaglandin (PG) production. This study was undertaken to assess the role of increased renal PG production in the change in renal function after BDL and to determine if these changes are mediated by the renin-angiotensin system. After baseline measurement of renal function, Sprague Dawley rats underwent either sham operation (SO) or BDL. Four days later animals received a single intraperitoneal injection of either 0.9% saline, 0.5 ml/kg (SO, n = 10; BDL, n = 10), or indomethacin, 5 mg/kg (SO + Indo, n = 10; BDL + Indo, n = 10), and renal function was reassessed. Plasma renin activity was measured at the end of the second study period. BDL resulted in a 40% decrease in Ccr (p = 0.000), a 38% decrease in UNaV (p = 0.002), a twofold increase in urinary 6-keto PGF1 alpha excretion (p = 0.005), and fourfold increases in urinary excretion of PGE2 (p = 0.006) and thromboxane B2 (p = 0.000). Indomethacin prevented the increase in urinary PG excretion otherwise seen with BDL and resulted in an additional 41% reduction in UNaV (p = 0.018). Further reductions in Ccr by indomethacin, however, were minimal and nonsignificant. Plasma renin activity did not differ among any of the groups. These findings indicate that the sodium retention associated with BDL is attenuated by the concomitant rise in renal PG production. This elevation in PG production, however, does not protect against the adverse effects of BDL on Ccr. Furthermore, the changes in renal function that occur after BDL do not appear to be mediated by the renin-angiotensin system. PMID- 2200158 TI - Development and reversal of endotoxemia and endotoxin-related death in obstructive jaundice. AB - Gut-derived endotoxemia has been implicated in postoperative complications in patients with jaundice. It is thought that absence of bile in the gut predisposes to portal absorption of endotoxin and endotoxemia is reversed by oral bile salt replacement or internal biliary drainage and return of bile to the gut, but not by external drainage. We believe that the importance of gastrointestinal bile flow has been overestimated and biliary obstruction and the integrity of hepatocyte and Kupffer cell function are more important in the development and reversal of endotoxemia. In experiment 1, serum endotoxin concentrations were measured in control rats (n = 10) after choledochovesical fistula (n = 15) and bile duct ligation (n = 15) and after relief of biliary obstruction by internal drainage (choledochoduodenostomy; n = 8) and sterile external drainage (choledochovesical fistula; n = 8), with a quantitative limulus assay. In experiment 2, mortality rates were measured in similar groups 48 hours after administration of oral endotoxin (5 mg/100 gm) and intravenous lead acetate (5 mg/100 gm). Bilirubin levels were elevated in bile duct ligation (192 +/- 13 mumols/L) compared with control animals and those with choledochovesical fistula, internal drainage, and external drainage (10.6 +/- 1.5 mumols/L). In experiment 1, significant portal endotoxemia and systemic endotoxemia occurred in bile duct ligation (portal, 130.4 +/- 12.9 pg/ml; systemic, 91.8 +/- 11.0 pg/ml) but not in choledochovesical fistula (portal, 49.3 +/- 17.1 pg/ml; systemic, 27.2 +/- 11.5 pg/ml). Relief of obstruction by both internal and external drainage reversed endotoxemia. In experiment 2, significant death occurred in bile duct ligation (13 of 15) but not in choledochovesical fistula (3 of 15), and relief of obstruction by both internal and external drainage prevented death. These results confirm that biliary obstruction is a more important factor than is gastrointestinal bile flow in the development and reversal of endotoxemia. PMID- 2200159 TI - Value of washings and brushings at fibreoptic bronchoscopy in the diagnosis of lung cancer. AB - A retrospective study was performed to evaluate the diagnostic yield for lung cancer from histological biopsy specimens and from washings and brushings for cytological examination taken at fibreoptic bronchoscopy. The records of 680 bronchoscopies were analysed. Of 300 patients eventually diagnosed as having a malignant lesion, 188 had had biopsy, washing, and brushing. Of these, 125 had endoscopically visible tumour (group A) and 63 had no abnormal findings or abnormal findings that were not diagnostic of malignancy (group B). In group A biopsy specimens gave a positive result in 76% of cases, washings in 49.6%, and brushings in 52%; biopsy material gave the only positive result in 22.4% of cases, washings in 2.2%, and brushings in 4.8%. In group B biopsy specimens were positive in 36.5%, washings in 38.1%, and brushings in 28.6%; biopsy gave the only positive result in 11.1% of cases, washing in 9.5%, and brushing in 3.2%. Washing had a higher diagnostic yield than brushing in group B. Biopsy and cytological examination of either washings or brushings were found to give over 95% of all positive results in group A, but in group B the combination of biopsy and washing was more often successful (94.3%) than biopsy and brushing (82.8%). It is concluded that for the maximum diagnostic yield in the diagnosis of lung cancer biopsy should be combined with cytology using both washings and brushings. PMID- 2200161 TI - Role of metabolism in dimethylnitrosamine-induced immunosuppression: a review. AB - Dimethylnitrosamine (DMN) has been characterized as a potent hepatotoxin, carcinogen and mutagen. As described below, immunotoxicity should be added to its profile of activity. Although a broad spectrum of immune parameters is affected by DMN, humoral immunity is particularly sensitive. In order for DMN to produce its traditional profile of toxicity it requires metabolic activation to reactive intermediates which alkylate macromolecules. Similarly, DMN also must be metabolized to produce its immunological effects. However, as this review suggests, the metabolism of DMN to an intermediate capable of suppressing the humoral immune response may be qualitatively and/or quantitatively different from that which mediates hepatotoxicity and genotoxicity. PMID- 2200160 TI - Molecular biology and respiratory disease. 4. Cancer genes. PMID- 2200162 TI - Protein translocation into reconstituted vesicles. PMID- 2200163 TI - Non-cholinergic actions of acetylcholinesterases: proteases regulating cell growth and development? AB - The enzyme acetylcholinesterase has a well-established function in limiting the duration of acetylcholine's action at cholinergic synapses. Until recently, the function of this enzyme in non-cholinergic tissues has been a mystery. Recent evidence suggests that some forms of acetylcholinesterase act as proteases to regulate cell growth and development. PMID- 2200164 TI - Propagation of an error: beta-sheet structures. PMID- 2200165 TI - Is the glutathione S-conjugate carrier an mdr1 gene product? PMID- 2200166 TI - The evolution of alpha/beta barrel enzymes. AB - Of the enzymes whose structure is known, roughly one out of ten has an eight stranded alpha/beta barrel domain. Structural and chemical evidence suggests that all of these domains may have diverged from a common ancestor. PMID- 2200167 TI - From comparisons of protein sequences and structures to protein modelling and design. PMID- 2200168 TI - Early days of ribosome research. PMID- 2200169 TI - Positively charged residues are important determinants of membrane protein topology. AB - Membrane proteins are found in a variety of conformations, with each protein spanning the membrane a set number of times and adopting a particular orientation. Positively charged residues, often located near the boundaries of transmembrane segments, appear to be involved in specifying the topology of membrane proteins. PMID- 2200170 TI - Is genetic code redundancy related to retention of structural information in both DNA strands? AB - We have noted that the sense-antisense relationships inherent in the genetic code divide the amino acids into three separate groups. The nature of the amino acids in each group may allow the polypeptides coded by the antisense strand to retain the secondary structure patterns of the translated strand. Also, this relationship requires all but eight of the codons in the eukaryotic code and all but four in the mitochondrial code. Thus, genetic code redundancy could be related to evolutionary pressure toward retention of protein structural information in both strands of DNA. PMID- 2200171 TI - What is the clock? Translational regulation of circadian bioluminescence. AB - An oscillation in the cellular level of specific proteins in the unicellular marine alga Gonyaulax is correlated with the prominent circadian rhythm of bioluminescence of living cells and persists under constant conditions. This regulation involves a daily bout of synthesis of a specific protein, which is controlled by the circadian clock at the translational level. PMID- 2200172 TI - Rosalind Pitt-Rivers and the discovery of T3. AB - The discovery of T3 as a major thyroid hormone brought international fame to Rosalind Pitt-Rivers in the 1950s. Here we reflect on the life and work of this distinguished biochemist who died in January of this year. PMID- 2200173 TI - The role of tumor necrosis factor in allograft rejection. II. Evidence that antibody therapy against tumor necrosis factor-alpha and lymphotoxin enhances cardiac allograft survival in rats. AB - In the previous study we demonstrated that circulating levels of TNF-alpha are elevated during liver allograft rejection and may precede clinical manifestations. The current study was designed to investigate the efficacy of antibody therapy against tumor necrosis factor-alpha and lymphotoxin (LT) in a rat heterotropic cardiac transplant model utilizing Buffalo donors and Lewis recipients. Control animals received no immunotherapy and experienced rejection on postoperative day 11 +/- 0.4 (mean +/- SEM). Experimental animals received immunotherapy either intraperitoneal or intravenous from days 1 to 10. The i.p. administered anti-TNF-alpha prolonged graft survival to 16 +/- 2.7 days (P less than 0.05 vs. controls); the i.v. administration prolonged survival to 15 +/- 1.4 days (P less than 0.004). Animals treated with i.p. anti-LT survived 17 +/- 1.7 days (P less than 0.002 vs. controls). Combination immunotherapy of anti-TNF alpha and anti-LT increased function to 21 +/- 2.2 days (P less than 0.001 vs controls). Conversely, administration of purified TNF-alpha or LT to graft recipients accelerated the time to rejection. Mean survival for both treatments was 7 days (P less than 0.001 vs. controls). Histologic examination of the transplanted cardiac tissue showed a typical pattern for acute rejection; there was no evidence of hemorrhagic or coagulative necrosis. In contrast, administration of purified TNF-alpha or LT to recipients of a syngeneic heart did not stimulate rejection. These data suggest that TNF-alpha and LT may play a role in the pathogenesis of acute allograft rejection. In addition, the mechanism appears to be distinct from that seen in TNF-alpha or LT-mediated cytotoxicity of tumor cells. PMID- 2200174 TI - Inhibition of anti-OKT3 antibody generation by cyclosporine--results of a prospective randomized trial. AB - To investigate the influence of therapy with cyclosporine on the generation of antibodies to OKT3, 51 renal transplant recipients previously maintained on CsA, azathioprine, and prednisone were allocated randomly either to receive 50% of their maintenance dose of CsA (group 1, n = 27) or to discontinue CsA (group 2, n = 24) during treatment with OKT3 for acute renal allograft rejection. In the month following therapy with OKT3, anti-OKT3 antibodies were detected in 11% of patients in group 1 and in 42% of patients in group 2 (P less than 0.02). No patient in group 1 developed antibody titers greater than 1:100, whereas 4 patients in group 2 developed titer greater than or equal to 1:1000. Rejection was reversed in 96% of patients in group 1 and in only 75% of patients in group 2 (P less than 0.03), suggesting that continued administration of reduced doses of CsA during therapy with OKT3 improves the short-term response to this monoclonal antibody. Results of this study suggest that concurrent administration of CsA during therapy with OKT3 inhibits the generation of anti-OKT3 antibodies and improves the response to this monoclonal antibody. PMID- 2200175 TI - Specific absorption of lymphocytotoxic alloantibodies by the liver in inbred rats. AB - It has been suggested that liver allografts are less sensitive to lymphocytotoxic antibodies than other organ allografts. In this experimental study in sensitized inbred rat recipients, we have used extracorporeal liver hemoperfusion to study interactions between the liver and lymphocytotoxic antibodies. Donor-specific liver hemoperfusion can delay hyperacute rejection of heart allografts and reduce the level of lymphocytotoxic antibodies. Immunofluorescence examination of the hemoperfused liver revealed deposits of C3 on Kupffer cells and of IgG on sinusoidal cells. In control rats in which a third-party liver, a donor-specific splenic or renal hemoperfusion was performed, heart allograft survival was less prolonged. The decrease in antibody levels was not significant and the deposit of C3 and IgG was much less evident. Similarly, previous blockade of the Kupffer cells of the donor-specific hemoperfused liver by dextran sulfate suppressed the effect of liver hemoperfusion. These results support the hypothesis that resistance of the liver to hyperacute rejection might be due to a massive and nontoxic absorption of lymphocytotoxic antibodies onto nonparenchymal liver cells. PMID- 2200176 TI - The influence of MHC and non-MHC genes on the nature of murine cardiac allograft rejection. I. Kinetic analysis of mononuclear cell infiltrate and MHC-class I/class II expression in donor tissue. AB - While normal cardiac tissue expresses low levels of MHC-class I, undetectable levels of MHC-class II antigens, and no mononuclear cell infiltrates, posttransplantation allogeneic donor cardiac tissue demonstrates dramatic increases of MHC-class I/class II expression coincident with the infiltration of the tissue with mononuclear cells. Results of this study demonstrate that the kinetics of MHC-class I/II antigen expression and the phenotype of mononuclear cell infiltrate are influenced, to a great degree, by the genetic H-2, intra-H-2 and non-H-2 incompatibility between donor and recipient strains of mice. Increases of MHC-class I precede class II expression in cells from donor cardiac tissue from completely allogeneic BALB/c, H-2-disparate B10.D2, B10.BR, and K, I A and I-E-disparate B10.T (6R) strains of mice implanted in B10 recipients. In contrast, increase in the level of MHC-class II precedes MHC-class I increases in donor cardiac tissue from H-2-identical but non-H-2-incompatible A. By and the I E + H-2D end-different B10.A(5R) donor tissue. The completely allogeneic, H-2 disparate or K, I-A, I-E-disparate donor cardiac tissue induced the infiltration of predominantly CD8+ T cells, whereas the non H-2 and I-E + H-2D end-different donor cardiac tissue induced the infiltration of predominantly CD4+ T cells. Finally, whereas bm1 donor cardiac tissue is rejected by B6 recipients by day 32, the (bm1 x bm12)F1 allografts are rejected by day 20, and both express MHC-class I antigens followed by MHC-class II antigens, and contain predominantly CD8+ T cells. In contrast, bm12 allografts are not rejected by B6 recipients, express chronic low levels of both MHC-class I and II antigens, and contain predominantly CD4+ T cells. Of interest is our preliminary finding that bm12 allografts placed in one ear of B6 recipients appear to modify the kinetics of MHC antigen expression and the predominant phenotype of mononuclear cell infiltrates in bm1 allografts placed in the opposite ear. Cumulatively, these data suggest that the type of genetic disparity between cardiac donor and recipient greatly influences the quantitative and qualitative host responses. PMID- 2200178 TI - The paradox of nicotinic acetylcholine receptor upregulation by nicotine. PMID- 2200177 TI - Significance of measurements of bronchial mucosal blood flow for the monitoring of acute rejection of transplanted lungs. PMID- 2200179 TI - A 'cocktail' strategy to assess in vivo oxidative drug metabolism in humans. PMID- 2200180 TI - This and that: on artificial fats and the first effective treatment for fits. PMID- 2200181 TI - Dopamine receptor subtypes: beyond the D1/D2 classification. AB - The D1/D2 dopamine receptor classification is widely accepted. However, intense investigative efforts over the last several years using pharmacological, biochemical and behavioral approaches have produced results that are increasingly difficult to reconcile with the existence of only two dopamine receptor subtypes. Recent developments, including cloning of the cDNAs and/or genes for several members of the large family of G-protein-coupled receptors, have revealed that heterogeneity in the pharmacological or biochemical characteristics of individual receptors often indicates the presence of previously unsuspected molecular subtypes. In this article, Marc Caron and colleagues have assembled the main lines of evidence that suggest the presence of several novel subtypes for both D1 and D2 dopamine receptors and predict that molecular cloning will, in the near future, confirm their existence. PMID- 2200182 TI - The history of pharmacology in The Netherlands. PMID- 2200183 TI - Remodeling of the vascular tree in hypertension: drug effects. AB - The primary aim of current antihypertensive therapy is to lower blood pressure through the reduction of peripheral vascular resistance. Resistance reduction is achieved primarily by interference with acutely acting pressor stimuli. However, recent research has stressed the importance of slow pressor stimuli, which act by gradually remodeling the vascular tree. Long-term remodeling is achieved by a chronic change in vessel number, vascular diameter or wall thickness, involving both physical and chemical factors. The chemical mediators belong to a group of endogenous growth-affecting factors. As Harry Struyker Boudier and colleagues explain in this review, although there are thus far no specific drugs to antagonize the effects of these factors, several therapeutically used antihypertensives influence their action. Moreover, the concept that vascular remodeling is important in hypertension offers exciting new therapeutic targets. PMID- 2200184 TI - VIP neurons in the cerebral cortex. AB - VIP-containing cells in the neocortex are intrinsic neurons of the bipolar type, which release VIP through mechanisms that involve Ca2+ and lipoxygenase metabolites. VIP receptors are coupled to cAMP-generating systems that are amplified by various neurotransmitters such as noradrenaline, histamine and GABA. Pierre Magistretti reviews the evidence that VIP neurons play an important role in the local regulation of metabolism in the cerebral cortex by stimulating glycogenolysis and altering cortical blood flow. PMID- 2200185 TI - Ultrastructural features of neuroendocrine differentiated carcinomas of the breast. AB - The ultrastructural patterns of neuroendocrine (NE) differentiated breast carcinomas are analyzed and discussed. Reports in the literature describe wide variations in the size of observed dense-core membrane-bound granules and discrepancies in their interpretation. In the present study 24 cases of breast carcinoma with recognized morphologic, histochemical, and immunocytochemical features of NE tumors were investigated. Five different types of dense-core granules of neurosecretory (NS) type (confirmed by the ultrastructural localization of chromogranin A) and five different cell types were recognized. Some amphicrine cells were found to contain both mucin and NS granules. Another notable ultrastructural feature of breast NE carcinomas was the presence of clear vesicles of presynaptic type, which correlated with expression of synaptophysin. PMID- 2200186 TI - Pigmented melanocytic schwannoma of the uterine cervix. AB - A 47-year-old woman had a lesion of the uterine cervix that presented clinically as a protruding or aborted leiomyoma. Grossly the tumor occupied a substantial portion of the cervical and endocervical region. Histologically it showed a spindle cell neoplasm arranged in large fascicles that penetrated deeply into the fibromuscular wall of the cervix. The tumor cells had abundant pink cytoplasm that contained considerable brown melanin granules confirmed by Fontana's stain. Cytologically nuclear pleomorphism, hyperchromatism, and giant nuclear forms were observed. Mitoses were also seen. Localized nuclear palisading was present. Electron microscopic examination of paraffin-embedded material revealed numerous premelanosomes and opaque granules that were compatible with mature melanosomes, thus confirming melanogenesis in the tumor. Tumor cells exhibited focal projections, and the connective tissue showed abnormal spacing of collagen. Basal lamina material was noted focally on tumor cell surfaces. Immunocytochemistry showed a positive reaction to S-100 protein and HMB-45 in tumor cell cytoplasm. PMID- 2200188 TI - [Modern calculi therapy]. PMID- 2200187 TI - [Prevention of thromboembolism in para-articular femoral fractures of the hip- results of a prospective randomized study of heparin-DHE and ASS-DHE]. AB - The effectiveness of prophylaxis of thromboembolism either by acetyl-salicylic acid (ASA) 0.5 g + dihydroergotamin (DHE) 2.5 mg three times a day or by Heparin 5000 IU + 0.5 mg DHE (HDHE) three times a day was compared in 404 patients, elder than 55 years, with fractures close by the hip joint. Effectiveness was proved daily clinical controls, perfusion scintigraphy on the day after admission, the fourth postoperative day and the day before discharge and by autopsy of the died patients. Clinical manifest thrombosis were seen on the operated legs in the HDHE group in 7.6% of the patients, in ASA-DHE-group in 15.6%, on the not operated leg under prophylaxis by HDHE in 3.8%, by ASA-DHE in 4.1% of the patients. Increased postoperative bleeding could be found under HDHE in 16.1% of the patients, under ASA-DHE in 9.3% of the patients, wound haematoma in 9.5% under HDHE and in 5.7% of the patients of the ASA-DHE-group. Superficial wound infections occurred under HDHE in 8.1%, under ASA-DHE in 5.7% of the patients, deep infections under HDHE in 0.5% and under ASA-DHE in 1.6% of the patients. Gastrointestinal bleeding under HDHE in 0.5% of the cases and under ASA-DHE in 3.1% of the cases. Prophylaxis had to be discharged in 7.6% of the patients of the HDHE-group and of 19.7% of the ASA-DHE-group. Pathologic perfusion scars should be found in 54.0% of the patients of the HDHE-group and in 54.9% of the ASA-DHE-group. Pulmonal perfusion became worse despite of prophylaxis by HDHE in 15.6% of the cases and despite prophylaxis with ASA-DHE in 17.6%. Pulmonal perfusion became better under HDHE in 11.9% and under ASA-DHE in 12.4% of the cases. The mortality was 9.7%. Fatal thromboembolism occurred under HDHE in three patients (1.4%) and under ASA DHE in three patients too (1.6%), after subcapital fractures in 0.5%, after pertrochanteric fractures in 2.1% and after subtrochanteric fractures in 6.25% of the patients without any significant difference between the two groups of prophylaxis. Fatal gastrointestinal bleeding had to be remarked in 1.0% of the patients of the HDHE-group and in 2.1% of the ASA-DHE-group, fatal infections in 0.5% of the patients of the HDHE-group and in 1.6% of the ASA-DHE-group. Fatal cardinal infarction could be seen under HDHE in 1.9% of the patients, under ASA DHE no fatal cardial infarction occurred.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2200189 TI - [Doppler ultrasound of penis arteries]. AB - In addition to pharmaco testing, pharmaco-Doppler sonography of the penile arteries is part of the basic work-up for erectile dysfunction. Insufficient training with the Doppler method, lack of standardized criteria for evaluation of the penis, and analysis of the Doppler curves all make it difficult to use Doppler sonography for the evaluation of impotent men. The aim of this study was to explain the principal criteria of the method and demonstrate the most important details for analyzing the form of the Doppler waves. Pharmaco-Doppler sonography includes the evaluation of blood-flow velocities within the dorsal and deep cavernous arteries of the penis before and after intracavernous application of a vasoactive drug. The following main criteria have proven to be most important for analysis of the Doppler curves: evaluation of the amplitude height, the actual wave form, differences between the left and right arteries and along the individual vessel, amplitude increase, and elevation of the curve baseline after pharmaco stimulation. The most frequent mistakes made during evaluation of the penile arteries are changes in the probe angle, pressure put on the artery by the probe during evaluation and a false estimation of the evaluation time after pharmaco stimulation. Recently, duplex sonography of the penile arteries has been introduced, and this method allows an accurate measurement of the blood-flow velocity and arterial diameter changes before and after application of the drug. Furthermore, additional calculation of the resistancy index permits determination of the vascular resistance and optimizes the evaluation of the penile arterial status. The technical details, the method, and the analyzation criteria are all explained in detail. PMID- 2200190 TI - [Pharmacoangiography and pharmacoangiodynography of the penis in erectile dysfunction]. AB - In 80 patients suffering from eretile dysfunction both pharmaco-angiography and pharmaco-Dopplerultrasonography of the penis were performed. The two methods showed a correlation of 96% with regard to the dorsal arteries and 92% with regard to the deep penile arteries. In a further 21 patients with erectile dysfunction pharmaco-angiodynography with the new QUANTUM device from Philips has been performed in recent weeks. The excellent illustration of vasculogenic details, even in the penile periphery, the exact measurement of the relevant hemodynamic parameters, e.g. peak flow velocity or pulsatility index, the short time needed for investigation and its non-invasive character give convincing evidence for the superiority of this new method over conventional angiographic procedures. This is also true when procedures for revascularization of the penis are planned. The only remaining indication for conventional pharmaco-angiography of the penis is now clarification of the connections in posttraumatic impotence of arterial etiology. PMID- 2200192 TI - [Diagnostic imaging in male reproductive medicine]. AB - Imaging methods are essential in the diagnosis of erectile dysfunction. With sonography the penile cavernous tissue and the deep arteries can be shown. This visualization is optimized by high-resolution ultrasonography with pulsed Doppler spectrum analysis or angiodynography. Pharmacocavernosonography combined with pharmacocavernosometry is the method of choice to verify pathologic venous leakage from the penis. Phalloarteriography is absolutely necessary before surgery for revascularization of the penis. In investigations of fertility sonography of the scrotum only plays a subordinate role, as an occlusion of the epididymis cannot be diagnosed in this way. In contrast, good visualization of any small intraparenchymous tumor of the testicle is possible. Transrectal sonography allows the best assessment of the vesicular glands. A persisting varicocele is visualized by retrograde phlebography of the internal spermatic vein. Antegrade phlebography of the spermatic vein with Valsalva maneuver is used by some workers in preference to the above-mentioned method, but has not yet been fully evaluated. Scrotal thermography can visualize a varicocele in a satisfactory manner. Obstacles to ejaculation can sometimes be visualized with retrograde urethrography and/or voiding urethrography. Focused x-rays of the sella turcica are necessary if there is any suspicion of a prolactinoma. Mammography will help to differentiate between gynecomasty and alimentary pseudo gynecomasty. CT and NMR are used to diagnose tumors of the adrenal and pituitary glands; these methods are rarely used to diagnose abdominal cryptorchidism. Radiologic representation of the ductus deferens with contrast medium (vasography) now has to be rejected as harmful and obsolete. PMID- 2200191 TI - [Pharmacocavernosometry and pharmacocavernosography in erectile dysfunction]. AB - In about 30% of patients with erectile dysfunction (ED), insufficiency of the corpus cavernosum, or a so-called venous outflow disturbance, pharmacocavernosometry (PCM) and pharmacocavernosography (PCG) are at present the most physiological modes of investigation for the use of vasoactive substances. The investigation technique is described and the results of 364 studies are reported. Using PCM, it is possible to quantify venous outflow disturbances and PCG permits them to be localized. In 111 patients, both PCM and PCG were performed, using a new cavernosography pump (AP300, Fresenius). Much lower flow values were found for maintenance flow than had previously been assumed (normal value: less than 15 ml; suspect: 15-30 ml; pathological: greater than 30 ml/min). Pressure drop time was the new measurement used, i.e., the time required for an intracorporal pressure drop from 150 to 50 mmHg. A value of greater than 1 min was established to be the normal value. In cases of pronounced insufficiency of the corpus cavernosum, the pressure drop time amounts to only a few seconds. Evaluation of 200 PCGs showed that an isolated pathological outflow via the deep dorsal vein of the penis could be demonstrated in only 10%, whereas in 72% the deep veins of the penis were involved. These results show that the operative indications for so-called venous outflow disturbances are considerably restricted. PMID- 2200193 TI - [Primary malignant melanoma of the distal urogenital tract. Case report and review of the literature]. AB - The primary manifestation of a malignant melanoma is rarely found in the female urethra and considerably less in urinary bladder. This article is based on a case report of a female patient who had to undergo numerous transurethral resections and died of such an escalating tumor. Malignant melanoma in the form of metastases are relevant to the urologist, because they are discovered frequently in the genitourinary tract. The symptoms and diagnostic procedures correspond to those of other urological carcinomas. Radical surgery is of major importance as therapy. PMID- 2200194 TI - [Prospective randomized multicenter phase III study of non-seminomatous testicular tumors of clinical stage II A/B]. PMID- 2200195 TI - [Comparative evaluation of the effectiveness of radiotherapy, surgery and combined treatment of stage I-II laryngeal cancer (T1-2NoMo) based on the data of a cooperative randomized study]. AB - During 1979-1987 269 patients with laryngeal cancer stage I-II were included into a cooperative randomized study: 111 patients had T1 and 158 patients, T2 tumor; 13% of patients showed cancer of the vestibular cord and 87% of them of the true vocal cord. 76 patients underwent surgery, 129 patients--radiotherapy, and 64 patients received combined treatment, i.e. radio- and chemotherapy (prospidine). The rate of relapses and regional metastases was 11.8 +/- 3.7% and 2.6 +/- 1.8% after surgery, 21.4 +/- 3.8% and 1.6 +/- 1.1% after radiotherapy, and 23.4 +/- 5.3% and 6.3 +/- 3.0% after combined treatment. In terms of the recurrence-free time surgical intervention showed the highest efficacy. With respect to the 5 year survival, measured in the above patients plus 42 patients operated on because of relapses and regional metastases, surgery of vocal cord cancer was effective in 100% in case of stage I, 97.4% in case of stage II; radiotherapy was effective in 91.7% in case of stage I, 88.8% in case of stage II, and combined treatment was effective in 100% in case of stage I and 70.3% in case of stage II; surgery of vestibular cord cancer stage II was effective in 100%, combined treatment in 88.9%, and radiotherapy in 68.6%. When vocal cord cancer involves the anterior commissure, ventricle, and space, preference should be given to surgery because relapses after radiotherapy were seen in 38-42%. Combined radio- and chemotherapy did not reduce the recurrence rate and therefore cannot be recommended for practical purposes. PMID- 2200196 TI - [Lymphocytic lymphoma of the nasal septum and myocardium]. PMID- 2200197 TI - [Helium-neon lasers in clinical and experimental otology]. PMID- 2200198 TI - Extraintestinal stages of Eimeria bovis in calves and attempts to induce relapse of clinical disease. AB - Monoclonal antibodies to all life cycle stages of Eimeria bovis were used in an avidin-biotin immunoperoxidase test to examine extraintestinal tissues from experimentally infected calves for developmental stages of the parasite. First generation meronts of Eimeria bovis were found in the mesenteric lymph nodes (MLNs) of three of four calves examined during the first 18 days of primary experimental infection. No extraintestinal stages were found in the MLNs of two calves examined 69 days after a primary infection or in five calves examined 6 months after a challenge infection. Tissue homogenates of liver, spleen, and MLNs from immune calves were not infectious for nonimmune recipient calves following oral or intraperitoneal inoculation indicating that infectious stages were not present in these extraintestinal tissues at the time of inoculations. Relapse of clinical coccidiosis and reoccurrence of oocyst shedding were not seen in E. bovis immune calves that were stressed by being put on a 16-week corticosteroid treatment program. PMID- 2200199 TI - A comparison of repair methods for gap healing in equine flexor tendon. AB - In nine horses (18 forelimbs), a 3 cm section of superficial digital flexor tendon was removed and the tendons were repaired with immobilization for 6 weeks and (1) no suture (n = 6); (2) a double locking loop tenorrhaphy with carbon fiber (n = 6); or (3) a double locking loop tenorrhaphy with size 2 nylon suture (n = 6). Clinical assessment, gross evaluation, morphometry, histology, and mechanical testing were performed on two limbs from each treatment group at weeks 6, 12, and 24. At weeks 6 and 12, the unsutured tissue was less mature than the tissue sutured with nylon. By week 24, the carbon fiber repair had breaking stress (mean, 12.5 M Pa) similar to the unsutured repair (mean, 10.6 M Pa). There was necrosis and a granulomatous foreign body reaction around the carbon fiber. The nylon suture repair had significantly greater strength per unit area (mean breaking stress, 20.4 M Pa) because of a smaller area of repair tissue in the gap (mean, 3.6 cm2). At week 24, the nylon suture repair tissue was the most mature with the least inflammation of the three repair methods. A nylon double locking loop suture was the preferred method for equine flexor tenorrhaphy of a tendon gap because of greater breaking stress, histologic maturity, biocompatibility, and the adequate functional and cosmetic outcome. PMID- 2200200 TI - Cystotomy closure. A comparison of the strength of appositional and inverting suture patterns. AB - Dorsal cystotomies were performed in 60 healthy dogs. Twenty bladders were closed with a single-layer interrupted appositional suture pattern, 20 with a two-layer interrupted appositional suture pattern, and 20 with a two-layer continuous inverting suture pattern. Four dogs from each group were euthanatized at hours 0, 3, 12, 18, and 24. Mechanical strength of the cystotomy closures was evaluated by calculating the circular bursting wall tension. The single-layer interrupted appositional suture pattern was as strong as both two-layer suture patterns at hours 3, 12, 18, and 24. The two-layer interrupted appositional suture pattern was as strong as the two-layer continuous inverting suture pattern during the first 24 hours. PMID- 2200201 TI - [The anesthesiological-resuscitation aspects and the medical problems of catastrophes]. AB - Anaesthesiological and resuscitation service is a special component of disaster medicine. It is of paramount importance in LSFA (life-supporting first aid) training of the lay public. Lack of knowledge and inadequate application of LSFA are estimated to increase the mortality rate of disaster victims by 40%. The paper discusses quantity and quality of anaesthesiological and resuscitation aid delivered immediately at the disaster scene, during triage before and after evacuation, during transportation. Much attention is devoted to pain management and infusion therapy performed at the disaster scene and during transportation. PMID- 2200202 TI - [The organization of protection and of the delivery of medical care for the population of the USA in catastrophes and other emergency conditions]. PMID- 2200203 TI - [Biochemistry of tears and its changes in pathology (review of the literature)]. PMID- 2200204 TI - [The study of protein-peptide hormones using genetic engineering methods (review of the literature)]. AB - Use of genetic engineering technique in cloning and sequence assay of cDNA and genes coding for mammal protein and peptide hormones is reviewed. Recent data on molecular aspects of gene reorganization in some inherited disorders are considered involving analytical methods for evaluation of gene activity, especially of genes coding for peptide hormones. Sequence assay of mRNA coding for mammal proopiomelanocortins (precursor of adrenocorticotropic hormone), beta lipotropic hormones of pituitary body, is discussed. PMID- 2200205 TI - [Proteolytic activity of blood cells in rheumatoid arthritis]. AB - Collagenolytic and neutral caseinolytic activities were studied in lysates of neutrophils, mononuclear cells and thrombocytes of patients with rheumatoid arthritis considering the steps and duration of the disease, before and after medical treatment. 5 healthy persons and 18 patients with rheumatoid arthritis were investigated. Specific caseinolytic activity (per 1 mg of protein) was increased in the patients neutrophils and monocytes 2.2- and 3.2-fold, respectively, while the activity per 10(6) cells was increased 1.5- and 2.2-fold, respectively. Specific collagenolytic activity was increased 1.4-fold in neutrophils and monocytes, whereas the activity per 10(6) neutrophils was increased by 20% and per 10(6) monocytes--near normal values. In thrombocytes collagenolytic activity was decreased by 40% and caseinolytic activity was similar to controls. Concentration of protein was decreased 1.5-fold in neutrophils and monocytes of the patients as compared with healthy persons. Proteinases are of importance in pathogenesis of rheumatoid arthritis and collagenolytic activity correlated most distinctly with development of the disease. After medical treatment collagenolytic activity was normalized in the patients cells studied, while caseinolytic activity was markedly decreased but remained above control values. Experiments with proteinase inhibitors enabled to detect major types of neutral proteinases in blood cells of patients with rheumatoid arthritis and to find some differences in the enzyme patterns in various blood cell populations. PMID- 2200206 TI - [New, registered specialty drugs in Austria. Diflucan, Fungata]. PMID- 2200207 TI - [Rhinocerebral mycoses caused by Mucoraceae species (mucormycosis). Case report and literature review]. AB - According to the literature and on the basis of the case reported in this paper of rhinocerebral mucoraceae mycosis we summarize the characteristic features as follows: mucoraceae--mycoses--common, but wrong term: "mucormycoses"--are a group of infections caused by members of the family mucoraceae (Mucor, Rhizomucor, Rhizopus, Absidia species)--most frequently by Rhizopus species. Primarily the fungi enter the pharynx or nose, local infections or trauma being a prerequisite. The most important predisposing factor is diabetes mellitus. Invading the tissue and causing vascular thrombosis the infection frequently takes an acute, often fulminating and fatal course. Acute sinusitis accompanied by swelling of the cheek and protrusion of the eye in a diabetic, particularly with acidosis, are pathognomonic. Diagnosis is confirmed by microscopic examination of infected tissue (unstained smear or histologically). Since systemically administered antifungals have not proved very effective in these myoses, mainly because an adequate tissue level can hardly be achieved, the most effective and curative treatment is surgical removal of infected tissue, simultaneous control of diabetes being mandatory. PMID- 2200208 TI - Hepatic hemangiomas. AB - There are 2 main and different forms of hepatic hemangiomas--those of early childhood and those of later adult life. The former, called infantile hepatic hemangioendothelioma, may be life-threatening due to arteriovenous shunting in extensive lesions resulting in cardiac failure. Although they may resolve spontaneously, if cardiac failure develops, they must be treated aggressively by arterial ligation or embolization. The adult form rarely gives rise to symptoms and should be left alone. Spontaneous rupture is extremely rare but may follow needle biopsy and it is in this group of patients that the occasional death has been reported. Biopsy should, therefore, be avoided. Symptomatic lesions should be resected in a specialized center where the morbidity and mortality of liver resection is acceptably very low. PMID- 2200209 TI - Hepatic vein and retrohepatic vena caval injury. AB - Retrohepatic venous injury presents as a rare but frequently lethal complication of trauma. The anatomic arrangement makes management of these injuries difficult at best. Operative exposure and isolation techniques ranging from cross-clamping the aorta, portal triad, suprarenal vena cava, and suprahepatic vena cava to the use of internal shunts are described in this report. Our experience from 1968 to 1987 with internal shunting techniques includes 27 patients. We have successfully resuscitated 12 patients for an acute mortality of 55%. We believe that this figure is high but compares favorably with published results. Late deaths from sepsis, disseminated intravascular coagulation, or multiple systems organ failure remain as significant causes of overall mortality. Many techniques have been successfully employed over the years in achieving vascular isolation of the liver. The methods all have their own merits, but the key factor in each is the recognition that they need to be employed. Conservative selection of patients is undoubtedly justified, but aggressive approaches should not be delayed until they are the methods of last resort. PMID- 2200210 TI - Conservative treatment of liver trauma. AB - A marked change toward a more conservative approach in the treatment of abdominal trauma has been noted, especially during the last decade. This change in regimen was first seen in the handling of splenic trauma, initiated by pediatric surgeons. Later, the concept of conservative management was also introduced among adults and it is now widely accepted. Here, an almost mandatory splenectomy has been replaced by attempts at various forms of splenic salvage. The development followed an initial report by King and Shumacker in 1952 on an increased susceptibility to overwhelming sepsis in splenectomized children, findings which later also were demonstrated among adults. It has also been shown that the bleeding from intraparenchymal lesions with an intact splenic capsule or minor capsular tears frequently ceases spontaneously, hereby making nonoperative management possible in selective cases. PMID- 2200212 TI - Surgical management of hepatic abscesses. AB - Amebic and pyogenic hepatic abscesses are rare liver lesions that may require surgical intervention. Amebic liver abscesses are more common in subtropical and tropical climates and in areas with poor sanitation. The majority of pyogenic liver abscesses are caused by infections in the biliary or intestinal tracts. These lesions can be differentiated on clinical grounds and by amebic serology. Ultrasound and computed tomography are the imaging techniques of choice. The initial management of amebic hepatic abscesses is treatment with amebicidal agents. Most patients respond rapidly so that surgery is reserved for patients with complications including secondary bacterial infection, impending rupture, or rupture into the pericardium or peritoneum. Patients with pyogenic hepatic abscesses require a prolonged course of antibiotics and appropriate drainage. Selected solitary abscesses can be managed with percutaneous abscess drainage. Similarly, some abscesses of biliary origin will respond to percutaneous biliary drainage. Surgical drainage has several advantages including: the ability to explore the abdomen for a source, excellent exposure of the entire liver, accurate assessment, sometimes with ultrasound, of the best drainage site, and access to the biliary tree for cholangiography and drainage. PMID- 2200211 TI - Current management of intrahepatic stones. AB - A high incidence of intrahepatic stones occurs in East Asia. The surgical management of intrahepatic stones is problematic because it is difficult to locate and remove all the stones and relieve the accompanying biliary strictures. Consequently, the rate of recurrent cholangitis is high. Many new techniques have been introduced to locate, fragment, and retrieve gallstones. Operative procedures to relieve biliary strictures have also undergone development. These new procedures and techniques have been applied to intrahepatic stones. The initial results are good. Whether these good results can be maintained in the long-term remains to be seen. PMID- 2200213 TI - Splenic abscess. AB - We present 7 cases of splenic abscess collected in our hospital from 1980 to 1988 as well as a review of 227 cases of the world literature. The signs and symptoms are nonspecific in all of them, fever being the most constant. Computed tomography scan followed by sonography were demonstrated to be the best methods of diagnosis. The treatment carried out on all of our patients was splenectomy followed by antibiotic coverage. Two of them died 15 days after the operation due to persistence of the septic state. In our review of the literature, we observe a rise in the population at risk for splenic abscess due to an increase in the use of immunosuppressive agents, to the higher survival of leukemic patients, and to the great incidence of drug abuse among others. Nevertheless, the advances in the use of sonography and computed tomography scan have made possible a more accurate diagnosis, therefore making possible an earlier treatment and a better prognosis. We believe that the treatment of choice is splenectomy with conservative treatment used only in specific cases where surgery represents a high risk for the patient. PMID- 2200215 TI - [Use of imaging procedures in arterial hypertension]. PMID- 2200214 TI - Comparison of deoxyribonucleic acid ploidy and nuclear expressed p62 c-myc oncogene in the prognosis of colorectal cancer. AB - A simultaneous flow cytometric assay of the nuclear expressed protein product of the c-myc oncogene p62 and deoxyribonucleic acid (DNA) ploidy in archival paraffin-embedded tumor material was undertaken in 179 patients with colorectal cancer, followed for up to 9 years. DNA ploidy showed a survival advantage for diploid tumors (chi 2(1) = 5.39, p = 0.020) and could be used to further divide patients with Dukes' A tumors (chi 2(1) = 4.87, p = 0.027) and Dukes' C tumors (chi 2(1) = 5.33, p = 0.021). By dividing patients into 2 levels of tumor expression of p62 c-myc, there was a trend for improved survival in patients with low expression (chi 2(1) = 3.65, p = 0.056). A combination of ploidy status and p62 c-myc expression improved upon survival prediction by ploidy alone in providing 3 groups (chi 2(2) = 7.86, p = 0.0197). While these results do not suggest a replacement for the Dukes' staging for prognosis (chi 2(3) = 33.82, p less than 0.00001), they strongly support the concept that enhanced expression of c-myc oncogene is associated with the progression of colorectal cancer. PMID- 2200216 TI - [The value of stress tests in arterial hypertension]. PMID- 2200217 TI - [Aortic isthmus stenosis]. PMID- 2200218 TI - [Transient cardiovascular hypertension]. PMID- 2200219 TI - [Secondary hormonal forms of hypertension]. PMID- 2200220 TI - [Drug-induced hypertension]. PMID- 2200221 TI - [Prognosis of arterial hypertension]. PMID- 2200222 TI - [Pathogenesis of congenital heart defects: fiction and truth]. AB - This is a review based on a description of a standardized method (microdissection + SEM) for study of human and animal cardiac development. Two examples of the analytical approach are given. In the first one, concerning the establishment of contact between the aorta and the left ventricle, the previous assumptions for "vectorial bulbus rotation" are disproved by more precise observations of normal cardiac development. Aorta is not transferred into the left ventricle but is connected to it by means of a "conduit" (aortic vestibulum) delimited by the fusion of the conotruncus ridges. For the second example the multilevel-analysis of pathogenesis of conotruncus septum defects in Keeshond dogs was selected. At the organ level, hypoplasia of the right ventricle was diagnosed, accompanied by hypoplasia of conus cushions. Tissue-level analysis indicated that the major cause of these hypoplasias is a decreased relative volume of the myocardium. Further study at the cell level showed that the number of mesenchymal cells in certain parts of conotruncus cushions is also diminished. Combining these observations with what is known about the architecture of cell proliferation in the embryonic heart, allows to formulate a hypothesis on a selective lesion of the right proliferation center, as one of the main causes of the observed anomalies. Further progress towards the subcellular and molecular level will help to complete the pathway from a gene defect toward an organ defect. PMID- 2200223 TI - [Liver cirrhosis--model and clinical practice]. PMID- 2200224 TI - [Missions in Argentine--here I heard the history of Sister Ingrid]. PMID- 2200225 TI - [Clinical trial of the new volatile anaesthetic agent isoflurane]. AB - In the article the author presents the main properties of isoflurane. The clinical testing was carried out in thirty maxillofacial patients undergoing surgery. A description of anaesthetic procedures is given. During this work special concern was paid to changes of arterial blood pressure and pulse rate under influence of isoflurane action, as well as to the recovery from it. A dependent decrease of arterial blood pressure has been observed. The pulse rate remained stable. During recovery from anaesthesia only a few adverse effects were registered. Isoflurane was estimated as safe and useful volatile anaesthetic agent. PMID- 2200226 TI - [A simple method for the isolation of immunoglobulin (Y) from the eggs of immunized hens]. AB - Hens were vaccinated with Salmonella typhi-murium and with serum-IgG from a goat. Antibodies (IgY) were isolated from the eggs by ammonium sulphate precipitation. The concentration of egg antibodies was equal or superior to the concentration of serum antibodies of the hen. The longlasting antibody plateau of 9 and 28 weeks, respectively, provides evidence of the high yields of specific IgY which can be collected from a single immunized hen. PMID- 2200227 TI - [Stratum-structure of the spinal nerves in the understanding of body structure]. AB - The main methodology employed in the progressive gross anatomy of today's Japan is typological anatomy (typologische Anatomie) as introduced by Seiho Nishi (1943; 1950; 1961). This typological methodology is sufficient to suggest the existence of a certain constancy between muscle phylogeny and innervation in spite of the classic theory of nerve-muscle specificity having been discredited. On the basis of findings obtained from the many recent Japanese studies including the author's study on the cervical plexus (Kida, 1987), it has been noted that the stratum-structure of the spinal nerves may be an important key for the phylogenetic understanding of animal body structure (Kida, 1988). 1) The stratum structure of the spinal nerves was initially observed only in the limb plexus by Furbringer (Schwalbe, 1981). At that time, it was accepted as the longitudinal strata corresponding to the portion occupied by nerve fibers to the flexors or the extensors (Bolk, 1902). This theory was effective for the systematic understanding of limb structure. 2) The stratum-structure of the spinal nerves was at first considered to be related to the concept of nerve-muscle specificity. After the review of Straus (1946) on the concept of nerve-muscle specificity, this concept was disproved and has since been generally regarded as a theory of the past, therefore stratum-structure is now treated independently of that concept. 3) However, recent Japanese studies have modified and progressed beyond the concept of the stratum-structure of the spinal nerves.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2200228 TI - [Three-dimensional analysis of the hip during growth]. AB - Ultrasonography provides a genuine breakthrough in the diagnosis of congenital dislocation of the hip and also helps considerably in evaluating the evolution and treatment. Current tridimensional analysis techniques, as described in this article, have revolutionized imaging. Operative situations may be simulated by a computer. Congruence, concentricity and coverage of the head may be evaluated. PMID- 2200229 TI - [Natural history of congenital hip dislocation during the first year of life]. AB - It seems obvious that congenital hip dislocation is determined by perinatal factors that are all the more "pathogenic" that the baby presents laxity (female sex or family laxity of the joints) and the hip is less mature (hereditary factor?). In our population, at the time of birth less than one child out of 1000 presents a dislocated hip that can be reduced (typical standard Ortolani sign). One or two percent present unstable hips that stabilize spontaneously in most cases. This stabilization can be expedited by correct diapering in abduction or may be hindered by such practices as wrapping infants from birth with their legs stretched and adducted, strapping the baby to a cradle-board, or perhaps even by putting the child to bed on its side. Stabilization may even be hindered by spontaneous asymmetrical postures that maintain the hip of the concave side of the baby in adduction, as in the pelvic obliquity syndrome of the newborn. The remaining children have a so-called stable hip which presents a variable degree of laxity on clinical examination and a variable degree of maturity on ultrasonography. The observation of established congenital dislocations in children who have been followed since birth (and such cases escape the most meticulous screening) suggests that in some hips there is no clear-cut dividing line between instability and laxity. Hips either stabilize or evolve into a fixed dislocation within the first three months, whereas it is only during the fourth month that X-ray examination may confirm the normality of such at-risk hips. Nevertheless, at that age, normality criteria are not very accurate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2200230 TI - [History and epidemiology of congenital hip dislocation in Brittany]. AB - Brittany is a region of France with a high rate of congenital dislocations of the hip (CDH). This was shown by Le Damany, who, in 1912, did a systematic screening of newborns and compared the number of CDH in Paris and Rennes. In Paris, there was 0.8% and in Rennes 3.6% CDH. This frequency is not generalized in Brittany, however; and Setter, who did a large survey in Finistere in 1961 and 1962, showed that the epicenter was the canton of Pont l'Abbe, also called "pays Bigouden". However, this disease did not occur in this region of France in earlier times. In 1795, Cambry, according to the "Convention de la Jeune Republique", travelled in Finistere from village to village and did not notice any limping women. This was a very serious and precise study, and we may conclude that there was no CDH at that time; the disease occurred later in "pays Bigouden". From these basic facts, certain hypotheses are considered. From the point of view of genetics, a mutation apparently occurred in the 19th century, but there is no reliable genetic study. Autosomic heredity with incomplete penetrance, with variable penetrance according to sex may be considered: it includes a multifactorial origin of the disease involving genetics, environmental, biochemical and ethnic factors, including local customs and traditions. PMID- 2200231 TI - Earliest diagnosis of congenital dislocation of the hip by ultrasonography. Historical background and present state of Graf's method. AB - Since Graf in 1978 introduced sonography into examination of hip dysplasia and hip dislocation, we survey an experience of more than 38,000 infant hips. At the present sonography of the infant hip is a standard and superior to traditional diagnostic methods especially in infants under three months of age, if the following minimum requirements are fulfilled: 1. THEORETICAL AND PRACTICAL TRAINING OF THE METHOD: anatomic identification (landmarks, standard situation, standard plane), description and nomenclature of the sonographic hip types according to GRAF, measurement (bony roof angle "alpha", cartilage roof angle "beta"), dynamic examination, therapeutic consequences and follow-up, points of weakness and errors of measurement. 2. CERTAIN TECHNICAL STANDARDS OF THE ULTRASOUND INSTRUMENT: linear scanner, 5 MHZ (newborn: 7.5 MHZ). POSITIONING DEVICE (patent: Fa Radl, A-8010 Graz-Austria) 3. SUFFICIENT DOCUMENTATION: projection similar to a ap-radiograph of the right hip, image scale never less than 1:1, black on white, two ultrasound scans per hip in the standard-plane. Suitable Systems: multiformat, dry copy, computer printout. Follow-up-studies have proved that in our region approximately five percent of hips under the age of three months require treatment, and that prognosis is better the earlier therapy is started. For this reason we recommend a sonographic screening of the newborn not later than six weeks of age. PMID- 2200232 TI - The importance of sonography and radiography in diagnosis and treatment of congenital dislocation of the hip. AB - The advantages of the sonography of the hip joint in the diagnosis and treatment of hip dysplasia in 1992 "policlinic" children and 1100 newborns are discussed and compared with radiological methods. The treatment concept at the Orthopadische Universitatsklinik Bonn is described as well as its modification after introduction of the sonography in the hip dysplasia screening-examination. These results confirm the necessity of making an early diagnosis. The osteonecrosis of the hip as a complication of the treatment of hip dislocation is discussed. PMID- 2200233 TI - [The value of echographic studies in congenital hip dislocation]. AB - Since the studies of R. Graf has echography of the hip replaced the standard X Rays of the pelvis in the early diagnosis of CDH after birth. The authors report their experience with this technique in 400 newborn children. The technical aspects and results are described. The study is original because the pediatric orthopaedic surgeon does simultaneously the clinical examination under echographic control. PMID- 2200234 TI - [Peri-acetabular reorientation osteotomy]. AB - A new technique to plan and perform a reorientation pelvic osteotomy around the hip joint in adolescents and adults is described. Planning is based on 3 dimensional reconstruction of the hip joint. The operation is simulated by computer before surgery to find the correction angles which optimize alignment both quantitatively (amount of femoral head covered) as well as qualitatively (joint congruency). These angles are then utilized at the time of surgery. A Smith-Petersen approach is always used to perform the osteotomy. The pelvic ring is not displaced, but nevertheless the acetabular fragment can be tilted without limitation around all 3 axes. Furthermore, linear displacement permits medialization of a lateralized hip joint. Stability is obtained by simple screw fixation. The posterior column remains mechanically intact, and thus no cast is required. Since 1984, about 200 peri-acetabular osteotomies have been performed. The success of correction was evaluated on plain radiographs using A P and "false profile" views as well as by CT. Conventional radiographs showed fully normalized VCE (Wiberg) and VCA (de Seze and Lequesne) angles and well-centered joints on the CT-based reconstructions. Four types of complications occurred: there were 2 cases with intra articular extension of the osteotomy; 1 transient femoral neuropraxia; 2 non-unions and 4 cases with ectopic ossifications which limited motion of the joint. The latter problem appear to have been eliminated by the administration of prophylactic indomethacin. Symptomatic fixation screws had to be removed after union in 13 cases. PMID- 2200235 TI - [Multicenter Belgian study of the results of total arthroplasty for persistent congenital hip dislocation]. AB - The SO.B.C.O.T. proposed a multicenter study of the results of total hip replacement performed in Belgium for treatment of severe congenital dislocation. Eleven departments with about 30 surgeons contributed to this retrospective analysis, in which cases treated in different centers with various techniques are reviewed. Difficulties in data collection are discussed. Owing to the variety of data, the article is divided in 2 sections: an inquiry or descriptive analysis of congenital dislocation of the hip treated in Belgium between January 1972 and December 1987; the midterm results achieved by different techniques. PMID- 2200236 TI - Combined anterior pituitary function test using CRH, GRH, LH-RH, TRH and vasopressin in patients with non-functioning pituitary tumors. AB - We examined 8 normal subjects and 16 patients with non-functioning pituitary tumors with a combined anterior pituitary test to evaluate the clinical usefulness of the test. Diagnoses included 9 of chromophobe adenoma, 3 of craniopharyngioma, 2 of Rathke's cleft cyst, and 1 each of intrasellar cyst and tuberculum sella meningioma. All subjects received hypothalamic releasing hormones: 1 micrograms/kg corticotropin releasing hormone (CRH), 1 micrograms/kg growth hormone releasing hormone (GRH), 500 micrograms thyrotropin-releasing hormone (TRH), 100 micrograms luteinizing hormone releasing hormone (LH-RH), and a relatively small dose (5 mU/kg) of lysine vasopressin (LVP). In the normal subjects, the addition of LVP potentiated the secretion of adenocorticotropic hormone (ACTH) induced by CRH, but had no significant effect on the secretion of other anterior pituitary hormones. In the combined test with 5 releasing hormones, the plasma ACTH and cortisol responses were not impaired in the majority of the patients before pituitary surgery. Serum thyroid-stimulating hormone (TSH), prolactin (PRL) and follicle-stimulating hormone (FSH) responses were not impaired in 82%, 70% and 67% of the patients, respectively, while the serum LH and GH responses were impaired in 67% and 73% of the patients, respectively. Following pituitary surgery, responses of these hormones to combined testing were similarly impaired in more than 75% of the patients. These results indicate that plasma ACTH, cortisol and serum TSH responses are fairly good before pituitary surgery but are impaired significantly after surgery. No subjects experienced any serious adverse effects related to the testing. These results suggest that combined testing with hypothalamic hormones is a convenient and useful method for evaluating pituitary function. PMID- 2200237 TI - Oat bran supplementation for elevated serum cholesterol. AB - The National Heart, Lung, and Blood Institute (NHLBI) has recommended intensive dietary treatment as first-line therapy for patients with high cholesterol levels. The NHLBI has also encouraged research into the effectiveness and safety of alternative diets and further study of human behavior as it relates to adherence to diets. Based on these recommendations and previous studies suggesting a hypocholesterolemic effect of oat bran dietary supplementation, 16 family practice outpatients with elevated cholesterol levels were enrolled in a 12 week study designed to assess the practicality and effectiveness of adding four oat bran muffins per day to the diet. Subjects were randomized into immediate intervention and delayed intervention groups. The combined group had a significant decrease in total cholesterol of 7.9 percent (p less than .03) and in LDL-cholesterol of 10.1 percent (p less than .03) but there was no significant difference with respect to lipid changes between the immediate group and the delay group when the delay group was serving as a control for the immediate group. The results taken in conjunction with evidence in the literature indicate that the simple addition of oat bran muffins to the diet of certain family practice outpatients is well tolerated and probably effective in lowering serum total and low density lipoprotein cholesterol. PMID- 2200238 TI - Interpretation of bone densitometry measurements: disadvantages of a percentage scale and a discussion of some alternatives. PMID- 2200239 TI - Prevention of glucocorticoid-induced osteoporosis. AB - There is increasing evidence that pamidronate and related compounds are effective in the prevention and treatment of osteoporosis. It is therefore of relevance to document the time course and mechanism of bisphosphonate action in this condition. To this end, the present study describes the biochemical responses to prophylactic treatment with oral pamidronate (APD, 150 mg/day) in 16 glucocorticoid-treated patients and contrasts them with those in 19 steroid treated control subjects. Measurements were made over a period of 12 months. The treated patients showed a fall in urine hydroxyproline excretion at 6 weeks associated with a reduction in serum ionized calcium concentration, a rise in serum 1,25-(OH)2D3, and a nonsignificant rise in serum bone gla protein (BGP). In contrast to BGP, serum alkaline phosphatase activity declined at 6 weeks, falling further at 3 months. Between 3 and 12 months, BGP levels paralleled those of alkaline phosphatase and hydroxyproline, all these being significantly below their initial values, and the other parameters returned to baseline. There was a gradual increase in plasma phosphate concentrations in the treated group over the 12 month period. It is concluded that pamidronate produces an acute and sustained inhibition of bone resorption followed by a more gradual reduction in bone formation. This transient dissociation results in a reduction in serum calcium, leading to a rise in serum 1,25-(OH)2D3, which in turn stimulates BGP production. Thereafter, indices of bone turnover remain subnormal but serum calcium and 1,25 (OH)2D3 return to baseline. PMID- 2200240 TI - American Society for Bone and Mineral Research awards. PMID- 2200241 TI - [The dissociation of a mutant strain of Streptomyces levoris 41-08, a producer of ichthiomycin]. AB - The population of Streptomyces levoris 41-08, producer of ichtiomicin, is established to be unhomogeneous and consisting of four types of morphologically different varieties: light grey, white, oligospore and asporogenous. The morphological varieties differ in their biochemical activity. The most promising for the ichtiomicine biosynthesis is the grey variant, some of whose representatives manifest up to 30% higher activity than the controls. The statistical processing of data shows that the oligospore and the asporogene variants with their limits of activity to 121.8 and 119.3% respectively are promising too, while the existence of white representatives in the population is not recommended since they are low-active minus variants. PMID- 2200243 TI - Occurrence of Enterobacteriaceae and E. coli in the intestine of the newborn by caesarean section. AB - It has been established that colonization of the gastrointestinal tract by Enterobacteriaceae and especially E. coli in newborn delivered by caesarean section occurs generally within the second day of life. On the 14th day, these bacteria inhabit the fecal flora of the majority of newborn. Hospital environment, as well as type of feeding do not seem to influence their frequency nor their level in the intestine of the infants born by caesarean section. PMID- 2200242 TI - [The immunomodulating properties of a glucomacropeptide from whey. I. The stimulation of resistance in mice]. AB - The immunomodulating effect on mice of three products glucomacropeptides obtained from whey with different carbohydrate and peptide components has been studied. After the preliminary application of the preparations at several doses the protective effect in infections with Salmonella typhimurium and Klebsiella pneumoniae increases to different extent. At lower doses fraction 3 increases in vitro the mitogen-induced proliferation of the thymus cells. The phagocytosis of the polymorphonuclear cells on the 24th hour after application of the three preparations is activated. The influence of the structurally different fractions on the immunoprotective effect is discussed. PMID- 2200244 TI - [The invasive properties of Escherichia coli O18 in relation to cell cultures and infections in inbred mice]. AB - Comparative analyses have been carried out on the dynamics of invasion of cell cultures from epithelioid (MK and HE-p-2) and fibroblast (mice fibroblasts) types with strain Escherichia coli 0 18 isolated and characterized earlier, as well as on the invasion of the viscera of inbred mice (BDF1) after subcutaneous (foot pad lesion test) and intravenous inoculation with the same strain. It was established that the realization of the invasion potential of E. coli 018 depends on the cell culture used: cell cultures of epithelioid type are much more sensitive. The development of the infectious process and the changes in the number of bacteria in the viscera of the inoculated mice for both ways of introduction of the agent were of the same type. The infectious process after subcutaneous inoculation was accompanied with serious orchitis and progressive inflammatory necrotic changes in the inoculated paws leading to demarcation of the whole limb. PMID- 2200245 TI - Dried fruit hypersensitivity and its correlation with pollen allergy. AB - A group of 102 patients (children and adults) with hypersensitivity to dried fruits and dermo-respiratory pathology underwent "in vivo" tests (skin tests) and "in vitro" tests (histamine release test, specific IgE) using a battery of foods and neumoallergens. We assessed immunoglobulin (IgG, IgA, IgM, IgE) levels as well as the complement (CH50), its components (C3, C4) and the possible presence of circulating immune complexes. Of the dried fruits the almond was the most sensitizing (89%, 87% and 68% of correlation between the clinical history and "in vivo" tests--skin tests--and "in vitro" tests--histamine release test and RAST--, respectively). As regards the other sensitizations, a hypersensitivity to peach was detected in 47% of the cases. As for the association between food allergy and pollen hypersensitivity, the highest percentages were for tree pollen (51%) followed by weeds (27%) and grasses (25%). The complement values did not show significant differences when they were compared with the control population. The statistical study correlating the clinical history with the results of the diagnostic methods--agreements between two or three tests--was positive (p greater than 0.05) for almond and peanut whereas it was negative (p less than 0.005) for hazelnut. PMID- 2200246 TI - Dysplastic nevi and malignant melanoma. AB - The incidence of melanoma has been steadily increasing, with a trend for this tumor to develop at younger ages. The only satisfactory treatment for melanoma is early intervention; therefore, routine screening for melanoma and dysplastic nevi during the general physical examination is important. The prevalence of dysplastic nevi is estimated to be 2 to 5 percent. Patients with dysplastic nevi appear to have at least a 6 percent lifetime risk of melanoma. In the most severely affected patients (those with a family history of dysplastic nevi and more than one melanoma), the lifetime risk may exceed 50 percent. Patients with dysplastic nevi merit periodic follow-up. Since these nevi tend to be familial, close relatives of affected patients may also benefit from a screening examination. Individuals at increased risk for melanoma may display one or more of the following risk factors: dysplastic nevi, freckling, tendency to sunburn and numerous common nevi. Such individuals may benefit most from education in sunburn avoidance, sunscreen use and self-examination for changing nevi. A better informed public and heightened physician awareness are the most effective means of reducing mortality from this virulent malignancy. PMID- 2200247 TI - Screening for asymptomatic bacteriuria, hematuria and proteinuria. The U.S. Preventive Services Task Force. AB - RECOMMENDATION: Periodic testing for asymptomatic bacteriuria is recommended for persons with diabetes and for pregnant women, and it may also be clinically prudent in preschool children. In general, dipsticks combining the leukocyte esterase and nitrite tests should be used to detect asymptomatic bacteriuria. However, urine culture is a more accurate screening test than is dipstick urinalysis, and it is recommended for detecting asymptomatic bacteriuria during pregnancy. Dipstick urinalysis for asymptomatic bacteriuria, hematuria and proteinuria may also be clinically prudent in persons over age 60. PMID- 2200248 TI - The preparticipation physical examination for sports. AB - Up to 25 million children and adolescents in the United States participate in some type of organized sports activity each year. Most of these young athletes receive an annual preparticipation physical examination. The purpose of the examination is to identify any conditions that might interfere with the athlete's ability to participate in a given sport. The criteria for disqualification are different for each sport. PMID- 2200249 TI - Lightning injuries. AB - Lightning kills or injures thousands of people in the United States each year. Injuries are caused by the effects of electrical, thermal and mechanical energy, and a wide range of clinical results, involving multiple body systems, is possible. Important differences exist between lightning victims and patients injured by fire or by other forms of electricity. In lightning victims, successful resuscitation is highly likely, even among patients with conventional signs of brain death. With proper management, long-term physical and psychologic sequelae of lightning injury are rare. PMID- 2200250 TI - Zidovudine for the treatment of HIV infection. AB - Zidovudine, the first widely used antiretroviral agent, prevents replication of the human immunodeficiency virus (HIV) by inhibiting reverse transcriptase. Its use in patients with acquired immunodeficiency syndrome slows progression of the disease and prolongs survival. Zidovudine also significantly reduces the rate of progression to AIDS in adults with asymptomatic HIV infection and CD4 T lymphocyte counts below 500 per mm3. The major toxicity of the drug is bone marrow suppression resulting in anemia or granulocytopenia, or both. Recently, lower doses have been shown to be effective and are associated with less toxicity. PMID- 2200251 TI - Myocardial stunning in dogs: preconditioning effect and influence of coronary collateral flow. AB - In open-chest dogs the left anterior descending (LAD) coronary artery diagonal branch was encircled with a pneumatic occluder. Pairs of ultrasonic crystals were inserted into LAD myocardium and remote normal muscle. The coronary artery was occluded for 5 minutes, followed by 10 minutes of reperfusion. This occlusion reperfusion cycle was repeated 12 times, and after a final 90-minute reperfusion period the hearts were removed and stained with triphenyltetrazolium chloride. No heart had evidence of necrosis. Baseline shortening normalized for end-diastolic length averaged 10.4 +/- 1.0% in the LAD area and 7.4 +/- 0.8% in the remote normal myocardium. When analyzed as a percentage of baseline, segment shortening in the normal myocardium was not significantly altered by LAD occlusion and reperfusion. In contrast, during occlusions the LAD myocardium paradoxically lengthened. With the initial reperfusion, shortening was significantly depressed to 28.6 +/- 8.6% of baseline. Although with subsequent reperfusions the return of function progressively decreased, the rate of deterioration was markedly attenuated after the first occlusion. By the end of the protocol many LAD segments lengthened paradoxically even after reperfusion, but in five hearts in which active contraction was preserved there was no significant change in regional function after the third cycle, suggesting a protective or preconditioning effect of earlier ischemia. There was a moderately good correlation between collateral blood flow and the degree of dysfunction following the initial 10-minute reperfusion (r = -0.73). This correlation deteriorated during subsequent reperfusion periods, implying that collateral blood flow can be a predictor of the extent of myocardial stunning only after the initial one or two reperfusion cycles. Thereafter other as yet unidentified factors make baseline collateral flow unimportant. PMID- 2200252 TI - New coronary artery disease index based on exercise-induced QRS changes. AB - Exercise-induced changes in Q, R, and S wave amplitudes have been reported to detect coronary artery disease but with low specificity, low sensitivity, or both; it was hypothesized that their incorporation into a composite index (Athens QRS score) might improve specificity and sensitivity. For this purpose 246 patients were analyzed retrospectively and 160 prospectively. All patients underwent maximal exercise testing with a standard Bruce protocol and coronary arteriography as part of the diagnostic evaluation for possible or definite coronary artery disease. The Athens QRS score was decreased as the number of obstructed coronary arteries increased (normal coronary arteries = 7.85 +/- 5.23 mm, one-vessel disease = 5.2 +/- 5.3 mm, two-vessel disease = -0.85 +/- 5.4 mm, three-vessel disease = -3.5 +/- 5.8 mm; p less than 0.0001); the score was unrelated to exercise-induced ST segment depression, and negative (less than 0) scores were always associated with coronary artery disease. An Athens QRS score of 5 mm predicted coronary artery disease with sensitivity ranging from 75% to 86% and a specificity ranging from 73% to 79%, values higher than those of the Q wave (75% and 50%, respectively), R wave (65% and 55%), and S wave (70% and 10%) and of the ST segment depression (62% and 70%). It is concluded that exercise induced changes in the QRS complex provide a useful index not only for the diagnosis but also for the assessment of severity of coronary artery disease. PMID- 2200253 TI - Nifedipine and isosorbide dinitrate alone and in combination for patients with chronic stable angina: a double-blind crossover study. AB - Since not all patients tolerate beta-blockers, the efficacy of nifedipine and isosorbide dinitrate was evaluated alone and in combination in patients with stable angina pectoris. The study was a randomized double-blind crossover design with patients titrated to maximally tolerated doses of both drugs. Phases included isosorbide dinitrate alone, nifedipine alone, and isosorbide dinitrate plus nifedipine in combination, with efficacy determined by stress testing. Eleven men and one woman patient with a mean age of 60 years and a mean of five anginal episodes/week completed the study. Patients were in New York Heart Association (NYHA) classes I, II, and III. With nifedipine alone compared with isosorbide dinitrate alone, patients had fewer angina attacks/week (p less than 0.02), exercised longer before experiencing angina (p less than 0.03), and had less ST segment depression during (p less than 0.03) or after (p less than 0.05) exercise. When patients received isosorbide dinitrate plus nifedipine, only time to onset of angina during exercise (p less than 0.05) was significantly different from the response with isosorbide dinitrate alone. Analysis of variance between nifedipine and isosorbide dinitrate plus nifedipine was not significant. Diastolic blood pressure with isosorbide dinitrate plus nifedipine (p less than 0.04) was lower than with isosorbide dinitrate alone. No significant differences in systolic blood pressure were noted between the treatment groups. The drugs alone and in combination were relatively well tolerated. Nifedipine alone may be superior to isosorbide dinitrate alone. The combination of isosorbide dinitrate plus nifedipine demonstrated no advantage over nifedipine alone compared with isosorbide dinitrate alone. PMID- 2200254 TI - Cardiac failure in coronary heart disease. AB - Cardiac failure, which used to be rare in coronary heart disease, is now its most common complication. Coronary heart disease can cause or appear as cardiac failure through one or more of 12 mechanisms: acute myocardial infarction, acute reversible ischemia, right ventricular dysfunction, cardiogenic shock, acute mitral regurgitation, ventricular septal perforation, cardiac free wall rupture, ischemic cardiomyopathy, ventricular aneurysm, coexisting diseases, iatrogenesis, and pseudoheart failure. An understanding of the responsible mechanism or mechanisms is essential not only for appropriate treatment but also for prognostication. Various therapeutic modalities, both medical and surgical, should be able to improve not only symptoms but also survival. Current efforts in the management of patients with cardiac failure as a result of coronary heart disease should be aimed at prevention, both primary and secondary. PMID- 2200255 TI - Acute ventricular septal rupture: perspectives on the current role of ventriculography and coronary arteriography and their implication for surgical repair. PMID- 2200256 TI - William P. Thompson, Samuel A. Levine--1935: systolic gallop sounds and mitral valve prolapse. PMID- 2200258 TI - A historical background of industrial hygiene. 1946. PMID- 2200257 TI - Comparative evaluation of cardioselectivity of metoprolol OROS and atenolol: a double-blind, placebo-controlled crossover study. AB - Cardioselectivity of a single oral dose of metoprolol oral osmotic (OROS) (14/190 mg) and atenolol (100 mg) was compared in 12 patients with reversible obstructive airway disease by assessing the dose-response curve to increasing doses of inhaled salbutamol. The beta-blocking activity of the two drugs, which was determined by measuring heart rate, blood pressure, and derived indexes at peak plasma drug levels, was similar. Both metoprolol and atenolol significantly reduced forced vital capacity and peak expiratory flow, with no difference between drugs. Atenolol but not metoprolol also significantly reduced forced expiratory volume in 1 second and specific airway conductance. Both metoprolol and atenolol shifted the dose-response curve of specific airway conductance to the right. The results indicate that the new OROS delivery system for metoprolol, which produces a relatively constant plasma drug level, provides a cardioselectivity comparable to or greater than that of atenolol at maximum plasma levels. PMID- 2200259 TI - July 1990 Consultants Listing. PMID- 2200260 TI - Health risk assessment and the practice of industrial hygiene. AB - It has been claimed that there may be as many as 2000 airborne chemicals to which persons could be exposed in the workplace and in the community. Of these, occupational exposure limits have been set for approximately 700 chemicals, and only about 30 chemicals have limits for the ambient air. It is likely that some type of health risk assessment methodology will be used to establish limits for the remainder. Although these methods have been used for over 10 yr to set environmental limits, each step of the process (hazard identification, dose response assessment, exposure assessment, and risk characterization) contains a number of traps into which scientists and risk managers can fall. For example, regulatory approaches to the hazard identification step have allowed little discrimination between the various animal carcinogens, even though these chemicals can vary greatly in their potency and mechanisms of action. In general, epidemiology data have been given little weight compared to the results of rodent bioassays. The dose-response extrapolation process, as generally practiced, often does not present the range of equally plausible values. Procedures which acknowledge and quantitatively account for some or all of the different classes of chemical carcinogens have not been widely adopted. For example, physiologically based pharmacokinetic (PB-PK) and biologically based models need to become a part of future risk assessments. The exposure evaluation portion of risk assessments can now be significantly more valid because of better dispersion models, validated exposure parameters, and the use of computers to account for complex environmental factors. Using these procedures, industrial hygienists are now able to quantitatively estimate the risks caused not only by the inhalation of chemicals but also those caused by dermal contact and incidental ingestion. The appropriate use of risk assessment methods should allow scientists and risk managers to set scientifically valid environmental and occupational standards for air contaminants. PMID- 2200261 TI - A review of Staphylococcus aureus exit-site and tunnel infections in peritoneal dialysis patients. AB - Staphylococcus aureus peritoneal exit-site and tunnel infections are a source of considerable morbidity for peritoneal dialysis patients. These infections are difficult to resolve, can lead to peritonitis, and often require removal of the peritoneal catheter. Staphylococcal nasal carriage is the major risk factor for S aureus exit-site infections and peritonitis episodes. In the future, the identification of patients who are S aureus nasal carriers and then treatment of the carriage state with rifampin may prove to be a means of decreasing infection rates. The best treatment for S aureus exit-site and tunnel infections has not been established. Treatment regimens in general use include oral antibiotics or intraperitoneal vancomycin. The optimal length of therapy is also unclear. Since the development of the disconnect peritoneal dialysis system, S aureus, rather than the Staphylococcus epidermidis, is the leading cause of peritonitis. To further decrease peritonitis rates, attention must now be directed at catheter related peritonitis episodes, with S aureus the most common cause of such episodes. Controlled, prospective studies designed to investigate methods of preventing and treating S aureus exit-site infections in peritoneal dialysis patients are needed. PMID- 2200262 TI - Autoimmunity and alcoholic liver disease. PMID- 2200263 TI - Multicenter study of recombinant human erythropoietin in correction of anemia in rheumatoid arthritis. AB - PURPOSE: To administer recombinant erythropoietin to patients with rheumatoid arthritis who had significant anemia, while monitoring hematologic and rheumatologic clinical responses as well as potential toxicity. PATIENTS AND METHODS: Seventeen patients with rheumatoid arthritis from five rheumatology care settings were studied. The patients had initial hematocrits of 34% or less and stable clinical status, and were not being treated with second-line drugs or corticosteroids. An 8-week randomized double-blind study involving various dosages of recombinant erythropoietin, as well as placebo, was followed by a 24 week open-label study in which dosage could be titrated to achieve a normal hematocrit. RESULTS: In the 8-week randomized study, four of 13 patients who received injections of recombinant erythropoietin showed a hematologic response, arbitrarily defined as at least a 6-unit increase in hematocrit. None of four placebo-treated patients showed a meaningful hematologic response. All 11 patients who completed the subsequent 24-week open-label study reached a normal hematocrit level at some time during the study, and 10 of 11 showed an increase of hematocrit 6 units or greater. At least one adjustment, i.e., an increase, decrease, or omission of the erythropoietin dosage, was required in all patients to maintain the hematocrit at a target range of 35% for women or 40% for men. Meaningful changes were not seen in patients' capacity to perform activities of daily living or pain levels during either the 8-week randomized study or the 24 week open-label study. No adverse effects were associated with recombinant erythropoietin therapy. CONCLUSION: Patients with rheumatoid arthritis showed excellent hematologic responses to recombinant erythropoietin, without toxicity, during careful monitoring for appropriate dosage adjustment, although a meaningful change in rheumatologic clinical status was not seen. PMID- 2200264 TI - Adverse drug effects attributed to phenylpropanolamine: a review of 142 case reports. AB - Phenylpropanolamine (PPA) is contained in about 106 products, over half of which are available over-the-counter (OTC). Most are cough/cold remedies; nine are OTC diet aids. More than nine million Americans were using OTC diet aids in 1981, making PPA the fifth most used drug in the United States, responsible for over $200 million in revenues. The safety of PPA remains controversial. Although most controlled studies indicate minimal pressor effects with recommended doses, adverse drug reactions (ADRs) continue to be documented. Since 1965, 142 ADRs have been reported in 85 studies, 69% of these in North America. Many such cases may go unrecognized. About two thirds of all ADRs occurred in females and in patients under 30. Of ADRs attributed to legitimately sold PPA products, 85% occurred after consumption of OTC products versus only 15% after prescription drugs. The PPA product often contained combination ingredients, or PPA was consumed along with additional drugs. An overdose of PPA was taken in about a third of the cases. After ingestion of non-overdose amounts, 82% of the ADRs were severe. The most frequent side effects involved symptoms compatible with acute hypertension, with severe headache the most common complaint. Twenty-four intracranial hemorrhages, eight seizures, and eight deaths (most due to stroke) were associated with PPA ingestion. We have summarized these data in an effort to alert clinicians to the prevalence of usage of PPA products and the potential for adverse effects. In patients who present with elevated blood pressure or signs of acute hypertension, especially hypertensive encephalopathy of undetermined origin, we recommend inquiry about recent ingestion of PPA-containing diet aids and cough/cold products and suggest having such patients remain upright rather than supine. PMID- 2200265 TI - A retrospective analysis of the natural history of primary IgA nephropathy worldwide. AB - The worldwide medical literature was reviewed to determine whether the prevalence, clinical presentation, and immunohistologic findings of primary IgA nephropathy were related to geographic areas. A total of 68 reports containing detailed clinical histories and laboratory findings were analyzed. The selected articles were grouped according to their geographic origin: Asia, Australia, Europe, and North America (Canada and the United States). Analysis of the data showed that IgA nephropathy is more frequent in the Asian area than in Australia, Europe, and North America. The male/female ratio indicates that males are more likely to be affected by the disease, particularly in the second and third decade of life. The appearance of the disease is characterized by microscopic hematuria and mild proteinuria in Asians, whereas gross hematuria is more frequent in American and European patients. At the time of renal biopsy, fixed microscopic hematuria is detected in a high percentage of patients in Asia and Europe, whereas macroscopic hematuria is more frequent in American patients. Mild renal lesions occur more frequently in Asian patients, while severe renal lesions and a high frequency of immunoglobulin and complement deposits are present in American and European patients. Differences encountered in this retrospective analysis may be influenced by two important factors: (1) the absence of urinalysis screening programs in the schools of Europe and North America, and (2) the different approaches to renal biopsy in the eastern and western parts of the world. Due to the high rate of renal insufficiency and end-stage kidney disease in European and North American patients with IgA nephropathy, it is recommended that a program of urinalysis screening in schools and an appropriate renal biopsy policy be adopted in the western areas of the world. PMID- 2200266 TI - Decreased phenytoin level after carboplatin treatment. PMID- 2200267 TI - Pseudocyst of the auricle. PMID- 2200268 TI - Detection of 'activated platelets' in the urinary sediments using a scanning electron microscope in patients with IgA nephropathy. AB - The presence of 'activated platelets' in the urinary sediments was studied by scanning electron microscopy (SEM) in patients with IgA nephropathy. The aim of the present study was to determine if the presence of activated platelets in the urinary sediments is correlated with glomerular injuries in patients with IgA nephropathy. Eleven patients with IgA nephropathy, 5 patients with thin basement membrane syndrome and 5 patients with membranous nephropathy were examined. The presence of platelets in glomeruli was also examined by immunofluorescence (IF). This study showed a correlation between the presence of activated platelets in the urinary sediments and the severity of glomerular injuries in patients with IgA nephropathy. The platelets were observed focally in glomeruli from such patients. It was suggested that the detection of activated platelets in the urinary sediments is useful in evaluating the degree of histopathological changes and/or prognosis of IgA nephropathy. PMID- 2200269 TI - Gram-negative arthritis with a simultaneous urinary tract infection in a renal transplant recipient. AB - Infections are common causes of morbidity in the renal transplant population, but infectious arthritis is rarely encountered. Gram-negative joint infections in the nontransplant population are often associated with simultaneous urinary tract infections. We report a case of Escherichia coli monoarthritis and a concomitant urinary tract infection in a renal transplant recipient and consider the possible predisposing factors for the infection. PMID- 2200270 TI - On psychoanalytic approaches to autism. AB - An analysis of the strengths and limitations of psychoanalytic approaches to autism serves to highlight the need for a theoretical scheme adequate to encompass social as well as cognitive development in autistic individuals. It is proposed that such a scheme will entail an account of normal development in which children's "object relations" feature prominently. PMID- 2200271 TI - Formal operational thinking: the role of cognitive-developmental processes in adolescent decision-making about pregnancy and contraception. AB - The role of formal operational thinking in adolescent decision-making about pregnancy and contraception is explored through an integration of the cognitive developmental and pregnancy-contraception literatures. The ways in which cognitive-developmental change mechanisms initiate or hinder formal thinking on pregnancy-contraception are considered, and implications for counseling pregnant adolescents are discussed. PMID- 2200272 TI - Holistic medicine and mental health practice: toward a new synthesis. AB - Holistic medicine offers insights and techniques which can significantly enlarge and enrich mental health practice. This approach, which recognizes the uniqueness of each patient, the centrality of the therapeutic partnership, and the primacy of self-care, regards the spiritual dimension as a vital enlargement of the biopsychosocial model. After outlining the holistic approach and its congruence with psychological thinking, this paper explores the ways in which holism may shape the future of mental health practice. PMID- 2200273 TI - Basolateral K conductance: role in regulation of NaCl absorption and secretion. AB - In this review we explore the possible role of basolateral K conductance (gK) in the regulation of salt absorption and secretion. This inquiry is prompted by a growing body of evidence which, taken together, suggests that basolateral gK is very labile and that alterations in basolateral gK may be a key feature in both stimulatory and inhibitory regulatory mechanisms. We first consider the role of basolateral gK in relation to models for salt absorption and secretion, particularly in relation to the maintenance of cellular charge balance and the obligatory coupling between the apical and basolateral membranes that is produced by transcellular current flow. Next, we review some of the experimental evidence that suggests that changes in basolateral gK are associated with transport regulation. The cellular mechanisms that are known to impact on K channel regulation are considered in a general way, and finally, we consider the use of integrated models for understanding possible coordinate regulation of apical and basolateral cell membranes. PMID- 2200274 TI - Insulin secretory capacity in endurance-trained and untrained young men. AB - Insulin secretion in response to glucose stimulation is reduced in endurance trained humans. In this study, a modified hyperglycemic clamp, with a superimposed arginine infusion and fat meal, was performed on eight endurance trained and nine untrained men to determine whether insulin secretory capacity is reduced by exercise training. Raising the plasma glucose concentration to approximately 450 mg/dl resulted in a plasma insulin response in the trained men that was approximately 64% lower than that of the untrained (peak values: 54 +/- 8 vs. 149 +/- 35 microU/ml; P less than 0.001). When a primed continuous infusion of arginine was superimposed on the hyperglycemia, the plasma insulin response was also markedly lower (66%) in the trained subjects, reaching peak values of 333 +/- 68 and 974 +/- 188 microU/ml for trained and untrained subjects, respectively (P less than 0.005). When insulin secretion was further stimulated during the arginine-infused hyperglycemia by the ingestion of a high-fat meal, peak insulin concentrations averaged 989 +/- 205 microU/ml in the trained compared with 2,232 +/- 455 microU/ml in the untrained subjects (P less than 0.01). The response of gastric inhibitory polypeptide (GIP) to the fat meal was delayed and blunted, suggesting that some enteric factor(s) other than GIP mediated the insulinotropic effect of the fat meal. The reduced plasma insulin response in trained people to the stimuli investigated suggests that regular exercise produces either several adaptations within the beta-cell or a single alteration of the beta-cell that results in an attenuation of the insulin secretory response to glucose, arginine, and fat ingestion. PMID- 2200275 TI - Hepatic nerves are not essential to the increase in hepatic glucose production during muscular work. AB - To establish the role of hepatic nerves in hepatic glycogenolytic and gluconeogenic regulation during exercise, dogs underwent a laparotomy during which the hepatic nerves were either left intact (C; n = 8) or cut (DN; n = 5). At least 17 days after surgery, dogs were studied during 150 min of treadmill exercise (12% grade, 100 m/min). Glucose production (Ra) and gluconeogenesis (GNG) were assessed by combining [3-3H]glucose, [U-14C]alanine, and indocyanine green infusions with arterial, portal vein, and hepatic vein sampling. Glucagon and insulin were similar at rest and exercise in both groups. Norepinephrine rose from 145 +/- 10 to 242 +/- 32 pg/ml by 150 min of exercise in C and from 150 +/- 25 to 333 +/- 83 pg/ml in DN. Epinephrine rose from 66 +/- 7 pg/ml at rest to 108 +/- 10 and 148 +/- 24 pg/ml after 30 and 150 min of exercise in C and from 90 +/- 15 pg/ml at rest to 185 +/- 33 (P less than 0.05 compared with C) and 194 +/- 36 pg/ml after 30 and 150 min of exercise in DN. Plasma glucose fell gradually from 108 +/- 2 and 106 +/- 3 mg/dl at rest to 96 +/- 4 and 92 +/- 8 by the end of exercise in C and DN, respectively. Ra was similar in C and DN rising from 3.2 +/ 0.2 to 8.7 +/- 0.6 and 2.6 +/- 0.2 to 7.5 +/- 1.1 mg.kg-1.min-1, respectively, by the end of exercise. Minimum and maximum rates of GNG from alanine, glycerol, and lactate were elevated in DN compared with C during rest and exercise. However, the exercise-induced changes in GNG were similar in both groups. In conclusion, nerves to the liver are not essential to the increased Ra and glucose homeostasis during moderate-intensity exercise. PMID- 2200276 TI - Effects of desipramine on norepinephrine clearance in congestive heart failure. AB - Elevated plasma norepinephrine (NE) in congestive heart failure (CHF) is caused by increased NE spillover and decreased NE clearance. To evaluate the effects of neuronal uptake blockade on NE clearance, we studied NE kinetics during steady state infusions of [3H]NE, before and after oral desipramine (DMI, 50 mg) in 11 patients with CHF and 8 normal volunteers. Baseline plasma NE was greater in the CHF group (637 +/- 56 vs. 271 +/- 32 pg/ml; P less than 0.001), NE clearance was lower in CHF (1.31 +/- 0.21 vs. 1.94 +/- 0.17 l.min-1.m-2; P = 0.026), and NE spillover was greater in CHF (4.71 +/- 0.78 vs. 3.04 +/- 0.35 nmol.min-1.m-2, P = 0.054). After DMI, plasma NE rose significantly in CHF (778 +/- 67; P = 0.008), and NE clearance decreased further in CHF (0.97 +/- 0.16; P = 0.024), but neither changed in normal subjects. NE spillover did not change in either group. There appears to be an enhanced effect of DMI on NE clearance in CHF patients. Two general mechanisms may be responsible for this finding, an increased concentration of drug, possibly caused by a decreased volume of distribution, and an increased sensitivity of neuronal amine pumps to DMI. Both mechanisms may reflect a more general abnormality of clearance of drugs and hormones related to abnormalities of tissue perfusion in CHF. PMID- 2200277 TI - Distribution and kinetics of glucose in rats analyzed by noncompartmental and compartmental analysis. AB - The steady-state kinetics and distribution of glucose were assessed using noncompartmental and various two-compartment models in rats that were infused with insulin (+/- euglycemic clamping), methylprednisolone (MP), or phlorizin (PHL) as well as rats injected with protamine-zinc-insulin (PZI) or rendered diabetic. Decreases in clearance of glucose (PCR) were greatest with insulin infusion, followed by PHL, MP, and PZI treatments. PCR decreased in diabetes to 25% of normal. With hyperinsulinemia and euglycemia, turnover rates were 1.18 times the rate of glucose infusion. In normal rats the ratio of the contents of the two compartments was 0.6-0.8 (depending on the model). Significant increases, of between 2.8 and 5.2, were observed with insulin infusion and between 0.8 and 1.8 with PHL, again depending on the model. Because PHL-induced changes in PCR are renal, these data suggest that variations in glucose distribution depend on changes in PCR as well as insulin. The intercompartmental rate constant decreased, and the noncompartmental volume of distribution increased to reflect the above changes. In non-steady-state studies, glucose release increased in response to insulin but not to PHL in contrast to other species. PMID- 2200278 TI - In vivo transport kinetics and distribution of taurocholate by rat ileum and jejunum. AB - The transport kinetics and distribution of taurocholate (TC) from the ileum and jejunum were evaluated in anesthetized Sprague-Dawley rats. Uptake and transport kinetics were determined after simultaneous administration of equimolar solutions of [3H]taurocholic acid ([3H]TC) in the ileum and [24-14C]taurocholic acid ([14C]TC) in the jejunum of anesthetized rats. At TC concentrations between 0.3 and 15 mM, total ileal absorption exceeded jejunal absorption 15- to 25-fold. The apparent Km and Vmax for ileal absorption of TC were 5.6 mM and 65.5 nmol.min 1.cm-1, respectively. Tissue distribution studies following uptake from the ileum and jejunum were done with 75Se-labeled homocholic acid taurine (75Se-HCAT). In the ileum, 82% of the 75Se-HCAT removed from the lumen was found in the bile, 10.6% was found in the ileal wall, and 7.3% was found in the liver. In the jejunum, 24.1% was found in bile, 0.6% was found in the liver, and 75.3% remained in the jejunal wall. These data show that the ileum is much more efficient and better equipped than the jejunum to take up and transport TC at concentrations up to 15 mM. PMID- 2200279 TI - Clearance and recycling of pulmonary surfactant. AB - In a steady state the rate of secretion of pulmonary surfactant lipids and proteins into the alveolar airspace must be balanced by the rate of removal. Several potential pathways for clearance have been identified including uptake by alveolar type II cells, which also synthesize and secrete surfactant components, uptake by other epithelial cells, and internalization by alveolar macrophages. A small amount of surfactant moves up the airways and through the epithelium endothelium barrier into the blood. Some of the surfactant lipids and proteins that are cleared from the alveolar airspace appear to be "recycled" in that they appear in the lamellar body, a surfactant secretory granule found in the type II cell. Some surfactant lipids are degraded, probably intracellularly, and the degradation products are reutilized to synthesize new lipids. Several factors have been shown to affect internalization by the type II cell and/or alveolar clearance including the surfactant proteins, lipids, and known stimuli of surfactant secretion. Surfactant proteins may be involved in regulating pool size by modulating both secretion rates and uptake rates, possibly by a receptor mediated process, although such receptors have not yet been identified or isolated. Clearance of surfactant lipids from the alveolar airspace is more rapid than clearance from the whole lung, and these two processes may be regulated by different factors. Elucidation of the factors that fine tune the balance between synthesis, secretion, and clearance of the lipid and protein components of surfactant awaits further investigation. PMID- 2200280 TI - The regulation of lung elastin synthesis. AB - The important role that elastin plays in the development and proper function of lung has long been recognized. Also, the intimate connection between pulmonary emphysema and the destruction of alveolar elastin has been well established. Understanding the mechanisms regulating pulmonary elastin synthesis is crucial to fully understanding these normal and pathological processes. In this article, we review recent literature on elastin structure, the elastin gene and its multiple RNA transcripts, and the different tropoelastin isoforms that are translated from these mRNAs. The similarity of lung and aortic elastin and the cellular origin of lung elastin are also discussed. We next examine the few studies addressing regulation of elastin expression during lung development, maturation, and aging. The search for modulators of pulmonary elastogenesis, which has yielded mostly negative results, is then reviewed. Finally, we present a cell culture model that has been developed to study the molecular basis of lung injury in pulmonary emphysema. PMID- 2200281 TI - Recent advances in respiratory neurobiology using in vitro methods. AB - Major advances in our understanding of the neurobiology of respiration are occurring due to the advent of mammalian in vitro preparations. These preparations include whole mounts of brain stem and spinal cord of the neonatal rat, thick and thin slices from various parts of the central nervous system (CNS), and isolated cells. A great advantage of such preparations is the ability to control precisely the extracellular environment and, by means of patch-type electrodes, the intracellular environment as well. Such control enables both membrane and intracellular mechanisms to be determined, thereby providing new insights into a variety of neuronal behaviors important to respiration. These behaviors include respiratory rhythmogenesis, the effect of intrinsic mechanisms on firing patterns, direct effects of neurotransmitters, and chemoreception. This commentary discusses these preparations and shows how they have recently been used to make major advances in our understanding of respiratory neurobiology. PMID- 2200282 TI - Lung epithelial ion transport and fluid movement during the perinatal period. AB - During fetal life, the mammalian lung is a secretory organ that serves no respiratory function. Its potential airspaces are filled with liquid that flows from the pulmonary circulation across the epithelium in response to the osmotic force generated by Cl- secretion of airway and distal lung epithelial cells. As birth approaches, net Cl- secretion across the respiratory tract epithelium decreases, and this is associated with a reduction in the flow of liquid into the lung lumen. The cause for this change is unknown, but several recent studies indicate that it may be related to alterations in the hormonal milieu to which the lung epithelium is exposed late in gestation. The switch from placental to pulmonary gas exchange at birth requires rapid removal of liquid from the lung lumen. During labor and the immediate postnatal period, the pulmonary epithelium changes from a predominantly Cl- secreting membrane to a predominantly Na(+) absorbing membrane, with resultant reversal of the direction of flow of lung liquid. There is considerable evidence that this change reflects an active metabolic process involving increased Na(+)-K(+)-ATPase activity in lung epithelial cells, which drives liquid from the lung lumen into the interstitium, with subsequent absorption into the pulmonary circulation. PMID- 2200283 TI - Plasticity in the airway epithelium. AB - Normal cell turnover as well as the response to injury require cell proliferation and differentiation. The airway epithelium maintains these processes throughout adult life. Controlled homeostatically, cell proliferation and differentiation usually restore, as an end point, the pseudostratified architecture of the normal mucociliary epithelium. After injury, however, cell proliferation and differentiation sometimes establish, as an end point, regions of metaplastic cells. In this brief review, we have tried to summarize research findings that 1) describe the development of metaplastic lesions in morphological terms, 2) identify cells the proliferation of which forms the basis of these lesions, and 3) identify molecular changes within these cells that control development of the metaplastic phenotype. PMID- 2200284 TI - Death resulting from motor vehicle immersions: the nature of the injuries, personal and environmental contributing factors, and potential interventions. AB - We present an epidemiologic characterization of deaths from motor vehicle immersions, based on 77 deaths in 63 motor vehicle immersions in Sacramento County, CA, during 1974-85. All persons were autopsied; all but one of the deaths were due to drowning. Average annual mortality rates per million person years were 12 for males, four for females, 30 for Hispanics, six for White non Hispanics, Blacks and Asians. Seventy-one percent of drivers and 60 percent of passengers had a blood alcohol concentration greater than or equal to 22 mmol/L. Most cases (57 percent) had an Injury Severity Score of 1 (minor injury) or 0 (no injury). Alcohol use was associated with higher Injury Severity Scores. Road curvature of 20 degrees or greater was far more common at crash sites than at matched control sites one mile away (OR = 6.57, 95% CI = 2.93, 14.71). Guard rail placement along highly curved sections of roadway may be an effective preventive measure. PMID- 2200285 TI - City directories as sources for survey work in low- and middle-income black communities. AB - Commercial directories and governmental lists of dwelling units in low income urban Black communities in four eastern cities were evaluated for completeness. With rare exceptions, less than 90 percent of dwelling units were included in any one list and no list adequately identified multiple dwelling unit structures. Since household income is likely to be lower among households in such structures, all lists tend to miss the very poor, i.e., those who may be at highest health risk. PMID- 2200286 TI - On quality of ambulatory care. PMID- 2200288 TI - Typing of southern African isolates of Plasmodium falciparum using monoclonal antibodies. AB - Antigenic diversity among 19 southern African isolates of Plasmodium falciparum was demonstrated using a panel of 9 monoclonal antibodies. Parasites obtained from single patients were heterogeneous. The antigen composition of 9 isolates was not stable with time in culture, particularly not with respect to 4 of the monoclonal antibodies. By the end of the investigation, 70% of isolates displayed an identical antigen pattern which was markedly different to any obtained in other parts of the world. Differences may be due to geographic origin of parasites or to variation in culture conditions. PMID- 2200287 TI - Permethrin-impregnated curtains and bed-nets prevent malaria in western Kenya. AB - The effectiveness of permethrin-impregnated (0.5 g/m2) bed-nets and curtains as malaria control measures was evaluated in Uriri, Kenya in 1988. One hundred five families were randomly assigned to 1 of 3 study groups (control, bed-net, or curtain). All participants were cured of parasitemia with pyrimethamine/sulfadoxine. Selective epidemiologic and entomologic parameters were measured weekly, while knowledge, attitude, and practices surveys were conducted at the beginning and end of the 15 week study. Plasmodium falciparum infections per person week at risk were significantly higher in the control group than in either the curtain group (5.42 vs. 2.35 cases/100 person weeks risk) or the bed-net group (5.42 vs. 3.77 cases/100 person weeks risk). The curtain group had fewer infections per person week at risk than the bed-net group (2.35 vs. 3.77 cases/100 person weeks risk). A difference was found in clinical malaria among the groups: 45% of persons in the bed-net and curtain groups vs. 30% of those in the control group reported no episodes of fever and chills (chi 2, P less than 0.05). Indoor resting Anopheles gambiae or An. funestus were found on 94 occasions in the control houses, but only twice in the treated houses during weekly visits to each house over the study period (chi 2 P less than 0.001). The pyrethrum knockdown method produced similar results with a total of 195, 23, and 3 An. gambiae and An. funestus collected in the control, bed-net, and curtain houses during the same period, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2200289 TI - Cutaneous leishmaniasis in French Guiana: a review. AB - A review of a 10 year investigation carried out by various institutions on cutaneous leishmaniasis in French Guiana is presented, with emphasis on epidemiology, clinical aspects, and therapy. PMID- 2200290 TI - Natural malaria infections in anophelines in Rondonia State, Brazilian Amazon. AB - The use of an Immunoassay for the detection of Plasmodium falciparum and P. vivax circumsporozoite (CS) antigens in anophelines has recently incriminated other malaria vectors besides Anopheles darlingi in the Brazilian Amazon. In this study we analyzed 12,336 field-collected anophelines from endemic areas in Rondonia for plasmodial infection. Sixty-one specimens from 6 species were positive: 47 An. darlingi, 5 An. triannulatus, 4 An. albitarsis, 2 An. braziliensis, 2 An. strodei, and 1 An. oswaldoi. As concerns the species, 41 anopheles harbored P. falciparum and 20 were infected with P. vivax. An. darlingi was the most important local vector, as it was the one most frequently found infected and the only one clearly related to areas where malaria transmission was being recorded. PMID- 2200291 TI - Quantity, analysis, and lethality of European and Africanized honey bee venoms. AB - Venom from Africanized honey bees (derived mainly from Apis mellifera scutellata) was compared with venom from domestic, European bees by study of lethality, immunological cross-reactivity, venom yield, isoelectric focusing (IEF) patterns, and melittin titers. The LD50s of European and Africanized bee venom by iv injection in mice were similar. In venom neutralization experiments, Africanized bee venom was mixed with antibodies from a beekeeper exposed only to European bees and used to challenge mice. Survival times of mice given these mixtures were significantly prolonged, indicating that human serum antibodies to European bee venom neutralized the lethal effects of Africanized bee venom. Reservoirs from Africanized bees contained less venom than European bees (94 and 147 micrograms venom/bee, respectively) and Africanized bee venom had a lower melittin content. The IEF patterns of venom from individual European bees varied considerably, as did IEF patterns of individual Africanized bees. Pools of venom from 1,000 bees of each population of A. mellifera showed noticeable but less obvious electrophoretic differences. The findings suggest that multiple stinging, and not increased venom potency or delivery, is the cause of serious reactions from Africanized bee attacks. PMID- 2200292 TI - Fate of the exposed saphenous vein graft. AB - Patients with functioning vein grafts may present with wound problems resulting in exposure of the graft. We reviewed the courses of 16 patients presenting with this problem to determine the causative factors and the most appropriate management of this therapeutic dilemma. Diabetes mellitus (11 of 16, 68.7%) and wound infection (12 of 16, 75%) were frequent pre-existing conditions associated with exposed venous grafts. All patients with exposed vein grafts were initially treated conservatively with regular application of moist sterile dressings, followed by split-thickness skin graft coverage of the wounds when clean. The wounds healed in 7 patients, whereas 9 patients developed complications of hemorrhage (7 patients) and graft thrombosis (2 patients). The outcome of therapy was highly dependent on the type of organism originally cultured from the wounds. The incidence of vein graft disruption was lowest when the wounds were sterile (25%) or when gram-positive bacteria grew (25%). Gram-negative infection uniformly resulted in disruption of the exposed venous graft. When a new graft was placed, the secondary graft became reinfected in all patients with gram negative primary graft infection. There were no instances of secondary graft reinfection when gram-negative bacteria were not present. These data suggest that the outcome of patients presenting with exposed vein grafts is highly dependent on the bacterial flora of the process. Vein graft disruption is frequent in patients with gram-negative infection, suggesting that these patients should be treated with distant graft ligation and extra-anatomic bypass. By contrast, patients without gram-negative infection may be successfully managed with local wound care. PMID- 2200293 TI - Distal embolization as a presenting symptom of aortic aneurysms. AB - The records of 302 patients who underwent abdominal aortic aneurysm (AAA) repair between 1985 and 1990 were reviewed. Two hundred and forty-eight patients (82%) were asymptomatic, while 32 patients (11%) had ruptured aneurysms. During this period, 15 patients (5%) presented with distal embolization as the first manifestation of their AAA. The preoperative embolic event resulted in limb threatening ischemia in 3 patients, digital ischemia in 11, and calf myonecrosis in 1. CT scan was performed in 14 of 15 patients demonstrating irregular, heterogeneous thrombus within the AAA. Only two of the AAAs were larger than 5 cm. Angiography demonstrated occlusive lesions but was not diagnostic for AAA in seven patients and resulted in three episodes of embolization. AAA was repaired with a tube graft in 4 patients while a bifurcated graft was required in 11 patients for aneurysmal (in 4 patients) and occlusive disease (in 7 patients) of the iliac arteries. All cases employed a transperitoneal approach, systemic heparin, and distal occlusion prior to aortic clamping. Complications included three major (below-knee) and five minor amputations, developing or worsening renal failure in five patients (33%), and death in two (13%). In comparison, mortality was 5% for elective repair and 66% for rupture during this same period. CT scan was safer and more informative than angiography. The morbidity of patients with AAA presenting with emboli is comparable with rupture. The risk of embolization does not correlate with size and indicates the potentially dangerous nature of small AAAs. PMID- 2200294 TI - Prompt diagnosis of acute cholecystitis in the critically ill. PMID- 2200295 TI - Penetrating neck trauma: a 5-year review of the literature, 1983 to 1988. AB - Penetrating neck trauma remains controversial: some trauma centers continue to pursue a policy of mandatory exploration while others advocate selective exploration. The literature regarding penetrating neck trauma published during the past 5 years is reviewed in this report. The majority of reports support selective exploration, and most civilian centers report a mortality of 3% to 6% regardless of the type of exploration performed. To clarify the rationale behind the selective management of penetrating neck wounds, current data on ballistics, ancillary diagnostic studies, and comparative costs are reviewed. Emergency room management and surgical follow-up, which vary according to the type of missile and the zone of the neck penetrated, are discussed. PMID- 2200296 TI - Immunotherapy of tree pollen allergy with a modified alginate conjugated birch pollen extract compared to an aluminium adsorbed extract. AB - The safety and efficacy of two birch pollen extracts, one chemically conjugated to alginate (Anjuvac) the other adsorbed to aluminium hydroxide (Alutard), were investigated in an open multicentre comparative study of 63 birch pollen allergic patients. Both extracts decreased the nasal symptoms during the birch pollen season. The changes in specific IgE and IgG were much the same in both treatment groups. The adverse reactions recorded were mild in both groups, but more frequent in the Anjuvac group, probably because of a more aggressive dose schedule though there were twice as many asthmatics in the Anjuvac group. The two investigated allergen extracts were useful alternatives for immunotherapy. PMID- 2200297 TI - Checklists and patient safety. PMID- 2200298 TI - Pre-induction behaviour of children. A review of placebo-controlled trials of sedatives. AB - Placebo-controlled trials of sedative premedication in children are reviewed in an attempt to determine which drugs have been shown to reduce the frequency with which children cry or appear apprehensive. Small samples and inappropriate statistical methods limit the value of many of the studies. Most of the drugs tested will, in sufficient dose, increase the proportion of children who are asleep. Only intramuscular opioid analgesics, either alone or in combination with other drugs, have been shown repeatedly to increase the frequency of calm behaviour in those who are awake. There is some evidence, however, that intramuscular placebo controls have a lower frequency of calm behavior than oral placebo controls. PMID- 2200299 TI - Pain on injection of propofol. Methods of alleviation. AB - A controlled randomised double-blind design was used to study the effect of lignocaine on the pain produced by intravenous injection of propofol. Patients received a 2-ml pretreatment solution with temporary venous occlusion, followed by an induction solution. One hundred and three patients were assigned to one of five groups: saline pretreatment, followed by induction with propofol plus saline 2 ml; lignocaine 20 mg pretreatment, followed by induction with propofol plus saline 2 ml; lignocaine 40 mg pretreatment, followed by induction with propofol plus saline 2 ml; saline pretreatment, followed by induction with propofol plus lignocaine 20 mg; or saline pretreatment, followed by induction with propofol plus lignocaine 40 mg. Pain was reduced significantly in all groups in which lignocaine was used and a dose of 40 mg was more effective than 20 mg. There were no significant differences in the incidence of pain among the groups which received lignocaine as pretreatment and the groups which received lignocaine mixed with propofol. Sixty-eight percent of patients who experienced pain or discomfort recalled it in the postoperative period. PMID- 2200300 TI - Pain on injection of propofol: the effect of injectate temperature. AB - A double-blind, randomised clinical study was undertaken to compare the effect of temperature on the incidence and severity of the pain experienced on injection of propofol. The number of patients who experienced pain and the severity of the pain were reduced significantly when propofol was administered at a temperature of 4 degrees C. The efficacy of propofol as an induction agent appeared to remain unaltered. PMID- 2200301 TI - Walter Stoeckel (1871-1961). A pioneer of regional analgesia in obstetrics. PMID- 2200302 TI - Rate-responsive pacemakers and anaesthesia. A consideration of possible implications. AB - A new generation of pacemakers has been developed in recent years which adjust the pacing rate according to changes in physiological variables. The selected parameters are affected during physical activity that involves an increased heart rate in healthy humans. The variables include body movements, QT interval, breathing, temperature, myocardial contractility, oxygen saturation and changes in blood pH which may be influenced during general anaesthesia, and can lead to unphysiological, high, pacing rates. It is important to be familiar with the pacemaker and its functions before administration of anaesthesia in order to prevent complications. Rate-responsive pacemakers in such situations should be programmed to exclude the rate-responsive function. PMID- 2200303 TI - Picogram quantitation of total DNA using DNA-binding proteins in a silicon sensor based system. AB - We report a rapid and reproducible method to quantify total DNA at picogram levels. Two high-affinity DNA-binding proteins are used to construct a sandwich assay and a semiconductor sensor is used for quantitation. Single-stranded DNA binding protein (SSB) from Escherichia coli is conjugated with a linker molecule, biotin, for specific capture of the DNA complex onto a membrane. Monoclonal anti DNA antibody is conjugated with an enzyme, urease, for signal generation. To detect DNA, a sample is denatured to form single-stranded DNA and then incubated with a reagent containing both DNA-binding protein conjugates and streptavidin. After incubation of the reagent with the DNA sample for 1 h at 37 degrees C to form a complex of streptavidin--biotin--SSB--DNA--anti-DNA--urease, the mixture is filtered through a biotin-coated nitrocellulose membrane which binds the streptavidin component of the complex. The unbound reagent is washed off the membrane, and then the captured DNA complex is detected with a light-addressable potentiometric sensor which measures the pH change catalyzed by the urease in the complex. This assay can detect 2 pg of DNA with a quantitation coefficient of variation of less than 10% in the range 10 to 200 pg. PMID- 2200304 TI - Analysis of protein digests by capillary high-performance liquid chromatography and on-line fast atom bombardment mass spectrometry. AB - An HPLC system incorporating a packed capillary C18 column has been utilized for high sensitivity peptide mapping and preparative collection for protein sequencing. This system combined with a Frit-FAB mass spectrometer interface also provides the ability to obtain molecular ions for peptides of enzymatically digested proteins in the time it takes to obtain an HPLC chromatogram. The low flow rates permit introduction of the entire column effluent into the mass spectrometer. Detection limits of 0.5-5 pmol are routine. Proteolytic digests of recombinant human methionyl growth hormone and protein carboxyl methyltransferase have been used to demonstrate the HPLC and mass spectrometer performance. PMID- 2200305 TI - Determination of phosphatidylcholine in a flow injection system using immobilized enzyme reactors. AB - Two alternative procedures are described for the quantitative determination of phosphatidylcholine in a flow-injection system utilizing immobilized enzymes. Phospholipase C from Bacillus cereus and phospholipase D from cabbage were covalently bound to the surface of controlled-pore glass beads and the enzyme derivatized beads were packed in small columns. In the first procedure, the phospholipase C column was connected with a second column containing coimmobilized alkaline phosphatase and choline oxidase. In the alternative procedure, the column packed with immobilized phospholipase D was connected with a column packed with immobilized choline oxidase. The hydrogen peroxide produced through the action of choline oxidase in both flow-injection systems was detected amperometrically. Both procedures are suitable for an accurate and rapid quantitation of phosphatidylcholine. The sensitivity of the method based on phospholipase C and alkaline phosphatase is higher than that using phospholipase D. Quantitation of phosphatidylcholine at the nanomole level can be easily obtained using the first method. PMID- 2200306 TI - A reactor permitting injection and sampling for steady state studies of enzymatic reactions at high pressure: tests with aspartate transcarbamylase. AB - A high pressure reactor for steady state studies of enzymes is described. It allows injection, stirring, and sampling without release of the pressure (up to at least 400 MPa). Thus, either substrate or enzyme can be injected to initiate an enzyme-catalyzed reaction whose progress can then be followed by measurements on samples taken from the reactor. The dead time of sampling is 10-15 s, which allows reactions with pseudo-first-order rate constants smaller than about 1 min 1 to be monitored. It can be used for any enzymatic reaction; unlike previously described high pressure apparatus, it is not limited to the study of enzymes whose activity can be directly followed by spectrophotometry. The use and reliability of this reactor is demonstrated by tests with aspartate transcarbamylase. The activity of this enzyme is enhanced by pressures of the order of 120 MPa. PMID- 2200307 TI - A highly sensitive method for determining both Mn- and Cu-Zn superoxide dismutase activities in tissues and blood cells. AB - A highly sensitive method for determining the superoxide dismutase (EC 1.15.1.1) in various tissues and blood cells is described. This method involves inhibition of a cypridina luciferin analog that is chemiluminescence dependent upon O2- generated by hypoxanthine-xanthine oxidase. Manganeous superoxide dismutase, which is sensitive to sodium dodecyl sulfate, was determined and calculated by subtraction of superoxide dismutase activity in tissue extract treated with this detergent (Cu-Zn superoxide dismutase) from that in untreated tissue extract (total superoxide dismutase). Both Mn- and Cu-Zn superoxide dismutase activities were expressed as equivalent nanograms of bovine erythrocyte superoxide dismutase per milliliter. Sensitivity limits of the chemiluminescence methods with 2-methyl 6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-alpha]pyraz in-3-one and 2-methyl-6 phenyl-3,7-dihydroimidazo[1,2-alpha]pyrazin-3-one as cypridina luciferin analogs were 1 ng and 2-3 ng of superoxide dismutase/ml, respectively. PMID- 2200308 TI - Amino and hydrazino alkyl benzoates as derivatizing agents for the separation and mass spectrometric analysis of oligosaccharides from bacterial lipooligosaccharides. AB - In an attempt to develop more sensitive and versatile methods for the structure analysis of oligosaccharides derived from lipooligosaccharides (LOS) of gram negative bacteria, amino and hydrazino alkyl benzoate derivatives were prepared. These oligosaccharide derivatives were separated by HPLC and then analyzed by liquid secondary ion mass spectrometry (LSIMS). Both the amino and hydrazino alkyl benzoates react with the free reducing termini of acid-treated LOS, increasing the hydrophobicity of the released oligosaccharides and allowing them to be separated by reverse-phase HPLC. In addition, these oligosaccharide derivatives now contain a sensitive uv chromophore for subsequent peak detection and improve the quality of the LSIMS spectra compared to underivatized oligosaccharides. However, the amino alkyl benzoates reacted poorly compared to the analogous hydrazino alkyl benzoates with 3-deoxy-manno-2-keto octulosonic acid (KDO), and oligosaccharides with KDO at the reducing terminus, especially when the oligosaccharide also contained phosphoethanolamine. Derivatization with the hydrazino compounds can be carried out quickly and under mild conditions using a minimal amount of reagent, and is therefore suitable for microscale analyses. The chromatographic and mass spectrometric characteristics of these derivatives make them excellent alternatives to permethylation and peracetylation techniques for the structural analysis of complex bacterial oligosaccharides derived from glycolipids. PMID- 2200309 TI - Native agarose-polyacrylamide gel electrophoresis allowing the detection of aminopeptidase, dehydrogenase, and esterase activities at the nanogram level: enzymatic patterns in some Frankia strains. AB - Nanogram amounts of soluble aminopeptidases, dehydrogenases, and esterases were detected by nondenaturing ultralow gelling point agarose-polyacrylamide gel electrophoresis (ULGA-PAGE). Cytosolic fractions from Frankia sp. were electrophoresed at 4 degrees C in the presence of Co2+, Zn2+, or Mg2+ ions. Then, aminopeptidases and esterases were revealed by simultaneous capture staining by using fast garnet GBC diazonium salt as the chromogenic coupling compound. Dehydrogenases were revealed by using nitro blue tetrazolium salt as electron acceptor. A variety of aminopeptidases, dehydrogenases, and esterases could be identified by their migration in ULGA-PAGE and by their sensitivities to NaCl, CoSO4, ZnSO4, and MgCl2 when assayed "ingel." The presence of agarose was essential for the detection of the complex enzyme patterns. The patterns were remarkably similar for the five Frankia strains isolated from Allocasuarina and Casuarina host plants and differed from those of Frankia strains isolated from Comptonia and Hippophae host plants. A nomenclature is proposed for aminopeptidases and other Frankia enzymes. The richness of the Frankia amino peptidases and esterases zymograms makes them adequate marker enzymes for taxonomical, genetic, or biochemical studies. Dehydrogenases might also be useful, although a more restricted number of bands were found with L-lactic and L malic acid as substrates. PMID- 2200310 TI - S1-nuclease enhancement of the ethidium bromide binding assay of drug-induced DNA interstrand crosslinking in human brain tumor cells. AB - A modification, using S1-nuclease, of a simple and sensitive fluorometric assay with ethidium bromide was developed for the measurement of cellular DNA interstrand crosslinking induced by bifunctional alkylators. Cells are lysed and treated with proteinase K and sodium dodecyl sulfate followed by extensive dialysis to yield intact high-molecular-weight DNA, free of contaminating proteins, on which the crosslink assay is then performed. The assay depends on the differential binding of ethidium bromide to single- and double-stranded DNA. Because of the higher ethidium bromide binding capacity of double-stranded DNA, the fluorescence retained after a heating/cooling cycle is directly proportional to the drug-induced cellular DNA interstrand crosslinking. We demonstrate that the sensitivity of this assay can be increased up to fourfold by including an S1 nuclease digestion step. This modified technique is simple and suited to the quantitation of low levels of DNA-interstrand crosslinking in cells. PMID- 2200311 TI - Direct analysis of bacterial fatty acids by Curie-point pyrolysis tandem mass spectrometry. AB - Although pyrolysis-mass spectrometry (Py-MS) has been used for bacterial taxonomy, many of the mass spectral peaks used for discrimination of organisms have not been correlated to known biomolecules. This work presents the discrimination of five bacterial species based on Py-MS patterns containing only peaks that can be correlated to fatty acids and fatty acid derivatives. These correlations were confirmed by pyrolysis-tandem mass spectrometry of authentic standards and the organisms. The pattern recognition procedures used gave better results when only the fatty acid peaks were used in the analysis than when full spectra were used. PMID- 2200312 TI - The metabolic response to stress: an overview and update. AB - Recent investigation has demonstrated that the response to stress is mediated by complex interactions between the nervous, endocrine, immune, and hematopoietic systems. Not only is the neuroendocrine system operative but monokines and lymphokines, such as IL-1, IL-6, and TNF, also play important roles. The discovery of these mediators, along with that of macrophage-derived substances that operate at the local wound level, such as platelet-derived, basic fibroblast, transforming, and epidermal growth factors, coupled with advances in molecular biology portends much for the future. The ability to alter the endocrine response with techniques such as epidural anesthesia, the ability to specifically block certain aspects of the response (e.g., with adrenergic and prostaglandin antagonists), and the ability to synthesize potential beneficial mediators with recombinant DNA techniques (e.g., GH) may allow for modulating the response to decrease debility and complications. PMID- 2200313 TI - Kawasaki syndrome. PMID- 2200314 TI - Adverse effects of large tidal volume and low PEEP in canine acid aspiration. AB - When normal lungs are ventilated with large tidal volumes (VT) and end-inspired pressures (Pei), surfactant is depleted and pulmonary edema develops. Both effects are diminished by positive end-expiratory pressure (PEEP). We reasoned that ventilatory with large VT-low PEEP would similarly increase edema following acute lung injury. To test this hypothesis, we ventilated dogs 1 h after hydrochloric acid (HCl) induced pulmonary edema with a large VT (30 ml/kg) and low PEEP (3 cm H2O) (large VT-low PEEP) and compared their results with dogs ventilated with a smaller VT (15 ml/kg) and 12 cm H2O PEEP (small VT-high PEEP). The small VT was the smallest that maintained eucapnia in our preparation; the large VT was chosen to match Pei and end-inspired lung volume. Pulmonary capillary wedge transmural pressure (Ppwtm) was kept at 8 mm Hg in both groups. Five hours after injury, the median lung wet weight to body weight ratio (WW/BW) was 25 g/kg higher in the large VT-low PEEP group than in the small VT-high PEEP group (p less than 0.05). Venous admixture (Qva/Qt) was similarly greater in the large VT-low PEEP group (49.8 versus 23.5%) (p less than 0.05). We conclude that small VT-high PEEP is a better mode of ventilating acute lung injury than large VT-low PEEP because edema accumulation is less and venous admixture is less. These advantages did not result from differences in Pei, end-inspiratory lung volume, or preload (Ppwtm).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2200315 TI - Value of ELISA using A60 antigen in the diagnosis of active pulmonary tuberculosis. AB - This investigation was undertaken to assess the effectiveness of an enzyme-linked immunosorbent assay (ELISA) using A60 antigen in ascertaining diagnosis in hospitalized patients suspected to have pulmonary tuberculosis (TB) but with negative sputum stains. Cultures were performed to confirm active or inactive disease. IgG and IgM antibody activity was determined by adding a 1:100 dilution of serum to plates coated with A60 antigen. After addition of peroxidase conjugated antihuman IgG or IgM and color development, optical density (OD) was determined. A total of 83 patients was studied, taking into account their current disease status and prior history. Using as a cutoff value the mean value +/- 2 SD measured in the negative culture, no TB history group, that is, OD = 0.50 for IgG measurements and 0.43 for IgM measurements, the sensitivity, specificity, and positive predictive value of IgG measurements were equal to 48, 71, and 50%, respectively. Using IgM measurements, these parameters were equal to 76, 98, and 95%, respectively. Combining the results of IgG and IgM measurements, sensitivity, specificity, and positive predictive value were equal to 68, 100, and 100%, respectively. Thus, the ELISA described here can greatly facilitate the diagnosis of TB in patients with negative smears. PMID- 2200316 TI - Serodiagnosis of tuberculosis using an ELISA with antigen 5 and a hemagglutination assay with glycolipid antigens. Results in patients with newly diagnosed pulmonary tuberculosis ranging in extent of disease from minimal to extensive. AB - Hemagglutination tests with three glycolipid antigens, A1, B1, and C, and ELISA with antigen 5 were done on serum from Chinese patients with pulmonary tuberculosis and from normal subjects in Hong Kong. Tests with all four antigens were of similar efficiency, giving positive results in 30 to 52% of 88 smear positive patients, in 16 to 22% of 37 smear-negative, culture-positive patients, in 5 to 13% of 76 culture-negative patients with radiologically active disease, in 5 to 11% of 217 culture-negative patients with inactive disease, and in 1 to 4% of 140 normal subjects. If tests were combined so that an overall positive was scored when all tests were positive, there was worse discrimination between patients and normal subjects; however, as suggested by the poor correlation between the results with pairs of the tests, better discrimination was obtained if an overall positive was scored when any of the tests was positive. A positive result in any of the four tests was found in 22% of all cases, including 58% of smear-positive patients, 32% of smear-negative, culture-positive patients, and 0.7% of normal subjects. PMID- 2200317 TI - Elevated concentration of soluble interleukin-2 receptors in serum of smokers and patients with lung cancer. Correlation with clinical activity. AB - Soluble interleukin-2 receptor (sIL-2R) levels in cigarette smokers and in patients with lung cancer were measured using an enzyme immunoassay. The rationale for our study was based on the fact that activation of T-cells is dependent upon the T-cell growth factor, interleukin-2, which may be regulated by its receptor, IL-2R. Measurements of circulating sIL-2R might be useful in the immune assessment of certain conditions. This study assessed elevated concentrations of circulating sIL-2R in smokers and in patients with lung cancer. The data show that healthy smokers, as a group, have an elevated level of sIL-2R compared with that in nonsmokers. Significantly higher than normal levels were found among light, moderate, and heavy smokers. Patients with lung cancer (squamous cell carcinoma [SSC] or adenocarcinoma [AC]) also have abnormally high sIL-2R levels. In the SCC group, the highest level of sIL-2R was among asymptomatic patients with well-differentiated tumors. Similarly, patients with SCC whose tumors were less than 3 cm in diameter had a significantly higher mean level of sIL-2R than did patients whose tumors exceeded 3 cm. The sIL-2R level in the SCC group also correlated with the tumor stage, with the highest level found among Stage I patients. In patients with SCC, but not in those with AC, the sIL 2R level was indicative of the extent of malignancy. These data support the concept that sIL-2R may be important in the pathogenesis of immune alterations associated with smoking and lung cancer. PMID- 2200318 TI - Mucosal inflammation in asthma. AB - Over the past decade, it has become increasingly recognized that airways inflammation is one of the major components of asthma. Until recently, measurements of bronchial responsiveness and mediators of allergic reactions were the only methods of studying pathogenetic mechanisms in asthma. With improved diagnostic procedures such as fiberoptic bronchoscopy, it has become possible to investigate these mechanisms and the resulting inflammatory changes in situ. BAL has highlighted the presence of mast cells and eosinophils and has given proof of their mediator participation in airways inflammation and hyperresponsiveness. Endobronchial biopsies have so far yielded results that are similar to those obtained from postmortem studies, although it appears that there are varying degrees of inflammation in living asthmatics. Even in mild disease, the histopathologic features of bronchial asthma are consistent with chronic inflammation. Indirect evidence obtained from allergen challenge leading to increased bronchial hyperresponsiveness during LAR, and direct evidence of inflammatory cells and their mediators in the airway mucosa and lumen after allergen challenge argue for an active role of cells in bringing about inflammatory changes. At present, however, it is not possible to relate precisely the findings obtained by bronchoscopy to the clinical presentation and progression of asthma. Cell activation with production of potent mediators of inflammation may be more relevant to inflammation than the simple presence of these cells in the airways. Almost all the inflammatory cells present in the bronchial wall and lumen have been implicated in the pathogenesis of mucosal inflammation in asthma, but with our current state of knowledge, none can be singled out as the most important contributor. The mast cell was the first to be investigated in depth, and despite the accumulation of large amounts of data concerning its ultrastructure and function, it remains uncertain to what extent this cell is involved in inflammatory responses. Thus, while its main role appears to be that of initiator of allergen-induced responses, the eosinophil has attracted more attention as a proinflammatory cell rather than as an antiinflammatory cell with a capacity to be selectively recruited from the circulation in response to IgE-dependent signals. The eosinophil secretes potent mediators that cause damage to the bronchial epithelium and lead to bronchoconstriction. The role of other cells is at present not as well defined.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2200319 TI - Clinical role of bronchoalveolar lavage in adults with pulmonary disease. AB - BAL remains a powerful investigative tool. In a short span of 20 yr, it has helped tremendously in understanding some of the aspects of the pathogenesis of diseases involving the lower respiratory tract. To realize its full potential in the diagnosis and management of diseases involving the lower respiratory tract, there is a great need for standardization of the technical aspects of BAL as well as processing and analysis of the BAL cellular- and fluid-phase components. Despite these hurdles, BAL has been found to be diagnostic in several infectious and noninfectious diseases involving the lower respiratory tract, and it provides valuable information that may be helpful in characterizing the prognosis and response to therapy in certain interstitial diseases of the lung. It is expected that with future research, in particular long-term prospective epidemiologic and clinical studies in pneumoconioses and in other interstitial lung disease, BAL will prove more valuable in the diagnosis and management of such disease. PMID- 2200320 TI - Screening for colorectal cancer: need for controlled trials. PMID- 2200321 TI - Screening for colorectal cancer. AB - Considerable indirect evidence, based on the natural history of colorectal cancer and the ability of tests to detect adenomas and invasive cancers, suggests that screening for colorectal cancer reduces mortality. Without screening, a 50-year old person at average risk has approximately a 530-in-10,000 chance of developing invasive colorectal cancer in the rest of his or her life and approximately a 250 in-10,000 chance of dying from it. Analysis of indirect evidence with a mathematic model indicates that screening persons for 25 years, from the age of 50 to the age of 75 years should reduce the chance of developing or dying from colorectal cancer by 10% to 75%, depending on which screening tests are used and how often screening is done. Screening for colorectal cancer is optional. A possible recommendation is that annual fecal occult blood tests and 65-cm flexible sigmoidoscopy every 3 to 5 years be done for average-risk men and women who are between 50 and 75 years of age. In addition to having annual fecal occult blood tests, persons with first-degree relatives with colorectal cancer can be offered barium enemas instead of sigmoidoscopies every 3 to 5 years. PMID- 2200322 TI - The origin and growth of medical journals. PMID- 2200323 TI - How long to abstain from eating red meat before fecal occult blood tests. PMID- 2200324 TI - Knowledge, culture, and science in the metropolis: The New York Academy of Sciences 1817-1970. PMID- 2200326 TI - Melanosis of the larynx. AB - A case of laryngeal melanosis is presented. This is followed by the analysis of the total of nine cases reported in the English literature. Patients are men in their sixth to eighth decade of life who present with hoarseness. Histopathologic findings include pigment deposits in the basal layer of the laryngeal epithelium. The possible relation of this lesion to carcinoma of the larynx is discussed. PMID- 2200325 TI - Nasopharyngeal craniopharyngioma. Case report and literature review. AB - Craniopharyngioma is an intracranial tumor that occurs rarely in the infrasellar region. Eight patients with craniopharyngioma located within the nasopharynx have been reported previously. These cases originated in the nasopharynx and involved the sella turcica (6), the sphenoid sinus (1), and the vomer (1). Craniopharyngioma usually originates intracranially. When there is no evidence of sellar involvement, the tumor most likely arises along the path of the craniopharyngeal duct. According to the neurosurgical literature, the optimal treatment consists of total surgical excision. Incomplete tumor removal is supplemented by adjunctive radiotherapy, which has been shown to significantly increase the survival rate. A patient with craniopharyngioma of the nasopharynx and paranasal sinuses who presented with nasal obstruction is reported. Radiographic studies were employed for tumor evaluation, and biopsy was done to establish the histopathologic diagnosis. Treatment included a combination of surgical excision and irradiation. PMID- 2200327 TI - Non-Warthin's tumor oncocytic lesions. AB - Oncocytes differ from other epithelial cells of salivary tissues in their excessive proliferation of mitochondria, in turn leading to a hypertrophy and hyperplasia of the chondriome. Oncocytic transformation is not a degenerative process, but rather a redifferentiation of the cells as they attempt to increase their output of high-energy phosphate. As oncocytes divide, their pathologic metabolic activity and mitochondrial phenotype are passed on to their progeny, and these cells produce salivary lesions that range from focal oncocytic metaplasia and hyperplasias to benign and malignant neoplasms--oncocytomas and oncocytic carcinomas. PMID- 2200329 TI - Measurement of human chorionic gonadotrophin (hCG): indications and techniques for the clinical laboratory. AB - The structure of human chorionic gonadotrophin (hCG) is so similar to that of luteinizing hormone (LH) that a variety of assay techniques have been devised to differentiate between these two hormones. The principal indications for measurement of hCG using these methods have not changed greatly over the past decade but the improvements in the sensitivity, specificity and the development of assays for free subunits and metabolic fragments have expanded the use of hCG assays. The review discusses the use of hCG measurement in a routine clinical immunoassay laboratory and emphasizes different requirements for clinical situations. PMID- 2200330 TI - Cerebrospinal fluid biochemistry in the diagnosis of multiple sclerosis. AB - The Poser criteria for diagnosing multiple sclerosis (MS) includes clinical, paraclinical and laboratory information. We studied the influence of cerebrospinal fluid (CSF) biochemistry results on the categorisation of patients with suspected MS. A retrospective study was made of 138 patients who had CSF samples sent over a 1 year period to the laboratory for examination for oligoclonal bands. Using the Poser criteria, 23 patients were diagnosed as having definite MS and one patient as probable MS. Cerebrospinal fluid biochemistry upgraded the categorisation from probable to definite MS in 16 of these 24 patients (66%). In this study, we found oligoclonal bands to be more sensitive in the diagnosis of MS (96%) than either the concentration of IgG in the CSF (43.5%) or the IgG expressed as a percentage of the total protein in the CSF (71%). We conclude that CSF biochemistry is a valuable investigation in the evaluation of patients with suspected MS. PMID- 2200328 TI - Aortic aneurysms--who should do them? AB - All patients undergoing abdominal aortic aneurysm repairs in a district general hospital between 1 January 1983 and 31 December 1987 were reviewed. Of the 76 cases, 53 were planned and 23 were ruptured aneurysms. The male:female ratio was 4.4:1, and the age range was 47-84 years (mean 67.6 +/- 6.97 years). Half underwent an ultrasound scan, showing a maximum diameter range of 3-12 cm. Fifty seven (75%) had tube grafts, and 19 (25%) bifurcation grafts. The 30-day mortality was 3.7% for planned cases, and 26% for ruptured cases. The principal operator in 55 (72.5%) cases was a consultant; consultant anaesthetists were involved in 61.3% cases. We conclude that aneurysm surgery can safely be performed in a district general hospital by a general surgeon with an interest in vascular surgery. PMID- 2200331 TI - Cerebrospinal fluid oligoclonal IgM in multiple sclerosis: analytical problems and clinical limitations. AB - A method for detecting cerebrospinal fluid (CSF) oligoclonal IgM is described. Concentrated CSF was separated by agarose isoelectric-focusing and blotted with poly(vinyldifluoride). A double-antibody immunoperoxidase technique with avidin biotin amplification was used to stain IgM. Special conditions were required to avoid cross-reaction with IgG. The method was applied to 99 patients on whom oligoclonal IgG analysis was performed. Positive IgM results occurred in 17 of the 27 patients positive for oligoclonal IgG, and in two patients negative for oligoclonal IgG, neither of whom had multiple sclerosis (MS). Fifteen of the patients positive for oligoclonal IgM had some IgM bands in their sera. Oligoclonal IgM was not found in the CSF of suspected MS patients without oligoclonal IgG, but occurred in several patients with oligoclonal IgG due to other diseases. As a test for MS, oligoclonal IgM was less sensitive than oligoclonal IgG and did not improve specificity. PMID- 2200332 TI - The usefulness of faecal haemoglobin, albumin and alpha-1-antitrypsin in the detection of gastrointestinal bleeding. AB - A pilot study was undertaken to find out whether faecal haemoglobin, albumin and alpha-1-antitrypsin from patients with gastrointestinal disorders could distinguish active bleeders from non-active bleeders and healthy volunteers. Alpha-1-antitrypsin is not as readily degraded by endogenous and bacterial breakdown as haemoglobin and albumin and consequently could be a better marker for occult bleeding. PMID- 2200333 TI - Ultrasensitive time-resolved immunofluorometry of human albumin in urine using monoclonal antibodies--a new assay for microalbuminuria. AB - We describe a two-site, sandwich methodology for human albumin in urine. In the assay, albumin binds to a solid-phase monoclonal antibody and to another monoclonal that is biotinylated. The immunocomplex is then quantified by adding streptavidin which is labelled with an europium chelator, using time-resolved fluorometry. The assay is extremely sensitive (less than 1 microgram/L and specific. A sample predilution of 251-fold or more is needed before analysis. The analytical parameters studied (precision, recovery, linearity, comparisons) were found to be satisfactory. The assay is simple to perform and is proposed as a non isotopic alternative to radioimmunoassay for the quantification of small amounts of albumin in urine for the purpose of assessing microalbuminuria. PMID- 2200334 TI - Pseudohypophosphataemia as a result of bilirubin interference. AB - During the routine use of a discrete analyser it was noted that, when the serum bilirubin concentration was greater than 50 mumol/L, there was interference with serum phosphate determination measured by the formation of unreduced phosphomolybdate using a bichromatic system of measurement. The degree of interference was assessed by comparison with a reduced phosphomolybdate method (molybdenum blue). The interference cannot be removed by changing the secondary wavelength or by the use of a sample blank. It is proportional to the serum bilirubin concentration, but is not significant when this is less than 50 mumol/L. The monochromatic non-reduced phosphomolybdate method compares well with the reduced method. PMID- 2200335 TI - Multicellular tumor spheroids in radiotherapy research (review). AB - Culturing of human tumor cells as multicellular spheroids can be a tool to study radiation responses. The degree of structural and functional differentiation in the primary tumor may be retained in spheroids rather than in conventional monolayer cultures. In the liquid overlay culture technique spheroids can be individually assessed for their responses to treatment, whereas in spinner flasks, large quantities of similarly sized spheroids can be produced. Studying the response of spheroids to irradiation can be performed on single cells obtained after disaggregation of these spheroids, or on intact spheroids, using cure and growth delay as endpoints. Clonogenic cell survival is especially difficult to perform on spheroids of human tumor cells. Modern calculation methods, however, may offer promising correlates between growth curves and single cell survival. Spheroids of human tumor cell lines show tumor type dependent radiation responses, offering an approach for comparison of radiosensitivity of tumor cell lines of different histologic origin. Contact effect, as a modifying factor of radiation response in spheroids, has especially been studied in murine cell lines. The use however, of human tumor cell lines, may offer new insight in this phenomenon. Radiobiologic hypoxia has been observed in spheroids of both murine and human origin. Reoxygenation after irradiation has also been described by radiobiologic parameters. So far, no physiologic reoxygenation processes after radiation treatment have been identified. In view of the clinical relevance of oxygen to radiation responses and treatment outcome, reoxygenation processes should be further elucidated in spheroids of human origin. Repair of potentially lethal damage in spheroids has been reported for only one murine cell line. In an indirect manner it has also been studied in spheroids of human origin. Sublethal damage repair has been studied rather extensively in murine cell line spheroids. However, only recently it has been reported in human tumor spheroids in relation to the clinical curability of the tumors of origin. Use of human tumor cell lines to study radiation responses of spheroids is necessary to determine tumor type dependent differences in several radiation related phenomena, such as reoxygenation, contact effect, and repair processes. PMID- 2200336 TI - Polymerase chain reaction for detection of invasive Shigella flexneri in food. AB - The polymerase chain reaction (PCR) was used to amplify a 760-base-pair (bp) fragment with the 220-kbp invasive plasmids of enteroinvasive Escherichia coli, Shigella flexneri, Shigella dysenteriae, Shigella boydii, and Shigella sonnei as templates. This PCR product was easily detected by agarose gel electrophoresis. A 210-bp AccI-PstI fragment lying within the amplified region was used as a probe in Southern hybridization blots and showed that the PCR-generated product was derived from the invasive plasmid. The application of PCR as a rapid method to detect enteroinvasive bacteria in foods was tested by inoculating lettuce with 10(4) S. flexneri cells per g in shigella broth base. Plasmid DNA was isolated from cultures of inoculated and uninoculated lettuce in broth after 0, 4, and 24 h of incubation. With the PCR, the 760-bp fragment was generated only from lettuce inoculated with S. flexneri, as shown by gel electrophoresis and confirmed both by Southern blotting and by nucleotide sequencing of the amplified region. Because the isolation of plasmid DNA, the performance of PCR, and gel electrophoresis all can be completed in 6 to 7 h, invasive enteric bacteria can be detected in less than 1 day. PMID- 2200337 TI - Enzyme-linked immunosorbent assay for Salmonella typhimurium in food: feasibility of 1-day Salmonella detection. AB - A microtitration plate, antibody-capture, enzyme-linked immunosorbent assay was developed for detection of Salmonella typhimurium. The assay utilizes a monoclonal detector antibody which shows no cross-reactions with non-Salmonella species and only a slight cross-reaction with one other Salmonella serotype. By using only one cultural stage (in a nonselective, chemically defined medium) prior to the enzyme-linked immunosorbent assay, low numbers of cells in food (10 cells 25 g-1) were detected in 19 h. Non-Salmonella competing organisms did not interfere with detection of S. typhimurium even when present in the ratio of 10(6):1 (non-Salmonella/Salmonella spp.). The assay shows the feasibility of rapid, 1-day testing for Salmonella spp. with antibody technology. PMID- 2200338 TI - Screening of aquatic samples for Vibrio cholerae serotype O1 by a dot-blot method and a latex agglutination test. AB - A dot-blot, enzyme-linked immunosorbent method and a latex agglutination test were studied for their abilities to detect Vibrio cholerae serotype O1 in aquatic samples by testing artificially contaminated water as well as samples from natural potential sources. Water samples were preenriched with alkaline peptone and then enriched with Monsur peptone water. For the dot-blot test, enriched cultures of organisms in a small portion of the Monsur peptone water were transferred to a polyvinylidene difluoride membrane with a microfiltration apparatus. The enzyme-linked immunosorbent assay was performed by using biotin labeled antibodies and avidin-biotin-peroxidase complex; brown dots developed in the wells that contained serotype O1 vibrios. Latex agglutination tests were performed by mixing 1 drop of the culture in Monsur with 1 drop of reagent coated with monoclonal antibody specific for antigen A. The sensitivities and specificities of the methods were compared with those of the colony-blot method, which identified individual colonies of V. cholerae O1 in mixed bacterial cultures on isolation media. Our results indicate that the dot-blot method is as sensitive as the colony-blot method and is useful for screening for V. cholerae serotype O1 even in specimens that are heavily contaminated with non-O1 vibrios. PMID- 2200339 TI - Molecular cloning of the 130-kilodalton mosquitocidal delta-endotoxin gene of Bacillus thuringiensis subsp. israelensis in Bacillus sphaericus. AB - A 3.7-kilobase (kb) XbaI fragment harboring the cryIVB gene (L. Thorne, F. Garduno, T. Thompson, D. Decker, M. A. Zounes, M. Wild, A. M. Walfield, and T. J. Pollock, J. Bacteriol. 166:801-811, 1986) which encoded a 130-kilodalton (kDa) mosquitocidal toxin from a 110-kb plasmid of Bacillus thuringiensis subsp. israelensis 4Q2-72 was cloned into pUC12 and transformed into Escherichia coli. The clone with a recombinant plasmid (designated pBT8) was toxic to Aedes aegypti larvae. The fragment (3.7 kb) was ligated into pBC16 (tetracycline resistant [Tcr]) and transformed by the method of protoplast transformation into Bacillus sphaericus 1593 and 2362, which were highly toxic to Anopheles and Culex mosquito larvae but less toxic to Aedes larvae. After cell regeneration on regeneration medium, the Tcr plasmids from transformants (pBTC1) of both strains of B. sphaericus were prepared and analyzed. The 3.7-kb XbaI fragment from the B. thuringiensis subsp. israelensis plasmid was shown to be present by agarose gel electrophoresis and Southern blot hybridization. In addition, B. sphaericus transformants produced a 130-kDa mosquitocidal toxin which was detected by Western (immuno-) blot analysis with antibody prepared against B. thuringiensis subsp. israelensis 130-kDa mosquitocidal toxin. The 50% lethal concentrations of the transformants of strains 1593 and 2362 against A. aegypti larvae were 2.7 X 10(2) and 5.7 X 10(2) cells per ml, respectively. This level of toxicity was comparable to the 50% lethal concentration of B. thuringiensis subsp. israelensis but much higher than that of B. sphaericus 1593 and 2362 (4.7 X 10(4) cells per ml) against A. aegypti larvae.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2200340 TI - Neutral sugar composition and gravimetric yield of plant and bacterial fractions of feces. AB - Separating dietary fiber from other polysaccharides in digesta and feces is necessary to understand its mechanisms of action. A gravimetric method that separates fecal plant and bacterial matter based on size and density was evaluated and modified to determine the plant and bacterial mass of lyophilized whole and blended rat and human feces. Three screen mech combinations (150 and 75 microns, 150 and 35 microns, 35 microns) were used with rat feces. Filtration of a homogenized rat fecal slurry sequentially through 150- and 35-microns-mesh screens versus 150- and 75-microns-mesh screens decreased the gravimetric recovery of bacteria from congruent to 35 to congruent to 25% of fecal dry weight and increased the plant fraction weight. Neutral sugar composition, determined by gas chromatography of alditol acetates, and bacterial counts of the fractions suggested that the decreased yield of bacterial fraction represented removal of plant material and not a loss of bacteria. Rat excreta contained 29.5% (dry weight) total neutral sugar, 88% of which was recovered in the plant material. Human feces containing wheat bran, fractionated with the 150- and 35-microns-mesh screens, was 21% neutral sugar, congruent to 65% of which was in the plant fraction. The plant fractions had more xylose and arabinose and less glucose than the bacterial fractions. Processing samples in a Waring blender had no adverse effect on the rat or human fecal bacterial counts. The use of this gravimetric method in combination with the sugar analysis of the fractions provided a better measure of plant and bacteria than only gravimetric yield. PMID- 2200341 TI - Nickel accumulation and storage in Bradyrhizobium japonicum. AB - Hydrogenase-derepressed (chemolithotrophic growth conditions) and heterotrophically grown cultures of Bradyrhizobium japonicum accumulated nickel about equally over a 3-h period. Both types of cultures accumulated nickel primarily in a form that was not exchangeable with NiCl2, and they accumulated much more Ni than would be needed for the Ni-containing hydrogenase. The nickel accumulated by heterotrophically incubated cultures could later be mobilized to allow active hydrogenase synthesis during derepression in the absence of nickel, while cells both grown and derepressed without nickel had low hydrogenase activities. The level of activity in cells grown with Ni and then derepressed without nickel was about the same as that in cultures derepressed in the presence of nickel. The Ni accumulated by heterotrophically grown cultures was associated principally with soluble proteins rather than particulate material, and this Ni was not lost upon dialyzing an extract containing the soluble proteins against either Ni-containing or EDTA-containing buffer. However, this Ni was lost upon pronase or low pH treatments. The soluble Ni-binding proteins were partially purified by gel filtration and DEAE chromatography. They were not antigenically related to hydrogenase peptides. Much of the 63Ni eluted as a single peak of 48 kilodaltons. Experiments involving immunoprecipitation of 63Ni-containing hydrogenase suggested that the stored source of Ni in heterotrophic cultures that could later be mobilized into hydrogenase resided in the nonexchangeable Ni containing fraction rather than in loosely bound or ionic forms. PMID- 2200342 TI - Combination of 16S rRNA-targeted oligonucleotide probes with flow cytometry for analyzing mixed microbial populations. AB - Fluorescent oligonucleotide hybridization probes were used to label bacterial cells for analysis by flow cytometry. The probes, complementary to short sequence elements within the 16S rRNA common to phylogenetically coherent assemblages of microorganisms, were labeled with tetramethylrhodamine and hybridized to suspensions of fixed cells. Flow cytometry was used to resolve individual target and nontarget bacteria (1 to 5 microns) via probe-conferred fluorescence. Target cells were quantified in an excess of nontarget cells. The intensity of fluorescence was increased additively by the combined use of two or three fluorescent probes complementary to different regions of the same 16S rRNA. PMID- 2200343 TI - Improved assay for surface hydrophobic avidity of Candida albicans cells. AB - A simple method that distinguishes among hydrophobic avidity levels of highly hydrophobic isolates of the pathogenic fungus Candida albicans is described. This method involves mixing polystyrene microspheres at different concentrations with a constant concentration of yeast cells and plotting the data in accordance with the Langmuir isotherm equation. A 10-fold difference between the C. albicans isolates with the lowest and highest avidity (KH) values was found. This method may also demonstrate that surface hydrophobic sites with different avidities are present within a yeast cell population. PMID- 2200344 TI - Kaposi's varicelliform eruption. Absence of ocular involvement. AB - The eponym Kaposi's varicelliform eruption (KVE) describes a characteristic syndrome of disseminated vesicopustules that occasionally complicates a number of dermatoses. Among these, the most common is atopic dermatitis, and the inciting agent is most often herpes simplex virus (HSV). Very few reports of ocular herpetic disease exist among the many cases of KVE reported in the literature, despite extensive cutaneous involvement with herpetic lesions. We describe 10 patients with KVE, none of whom have developed evidence of herpetic ocular disease despite widespread facial involvement in all patients. All random conjunctival swab cultures performed in 3 patients were positive for growth of viable HSV. Although ocular exposure to HSV may commonly occur in KVE, ocular pathology due to this virus does not appear to be a common sequela. PMID- 2200345 TI - HLA antigens in lichen sclerosus et atrophicus. AB - Several reports have found conflicting data regarding the association between lichen sclerosus et atrophicus (LSA) and HLA types. Association with HLA-A31 and B40 has been noted, whereas another report found no correlation. We are the first to specifically examine HLA types in white patients in the United States. We have found a significant association between LSA and HLA-A29 and -B44 individually and an even stronger association with the combination of A29 and B44. A review of previous LSA-HLA studies, as well as several reports of HLA typing in familial LSA, is discussed, with consideration given to possible reasons for the discrepancies among the various studies. PMID- 2200347 TI - Sweating in ectodermal dysplasia syndromes. A review. AB - Ectodermal dysplasia syndromes are currently classified based on constellations of clinical features, a major one of which is the presence or absence of normal sweating. The evaluation of sweating in these disorders has not been performed in a standardized manner, as is shown here in this literature review of a sampling of ectodermal dysplasia syndromes. Accurate evaluation of sweating is important not only in enabling more effective diagnosis and classification of patients with these syndromes, but also in aiding genetic counseling by potential detection of carrier states. A review of the variety of sweat tests currently in use is presented. PMID- 2200346 TI - Disseminated Mycobacterium chelonae subspecies chelonae infection with cutaneous and osseous manifestations. AB - A 75-year-old man who had been receiving corticosteroids for treatment of chronic obstructive pulmonary disease presented with nodulopustular skin lesions, bone pain, and constitutional symptoms. Evaluation revealed a disseminated infection with Mycobacterium chelonae subspecies chelonae, with cutaneous and osseous involvement documented by histopathologic studies and cultures. The bone involvement is a novel observation for this subspecies. The patient was successfully treated with a three-drug regimen of tobramycin sulfate, erythromycin stearate, and ciprofloxacin hydrochloride. We present a discussion of the case in the context of the literature. PMID- 2200348 TI - Interferon. Coming of age. PMID- 2200350 TI - [Critical evaluation of teflon in urology]. PMID- 2200349 TI - Varicella-zoster virus disease in patients with human immunodeficiency virus infection. PMID- 2200351 TI - [Female urethral stenosis caused by vulvar dystrophy]. AB - A rare case of chronic obstructive uropathy from urethral stenosis secondary to valvular dystrophy presenting as complete acute urinary retention preceded by progressive dysuria in a 77-year-old patient is described. Patient age and ultrasound evidence of bilateral hydronephrosis led us to suspect obstructive anuria from a neoplasm. The literature is reviewed, highlighting the role of gynecological disorders in the etiopathogenesis of female obstructive uropathy. PMID- 2200352 TI - [Cancer of the bladder and hemodialysis]. AB - Of 324 patients on long-term dialysis treatment, 14 developed malignant tumors. Of these, 4 had bladder tumors. The increased frequency of malignant tumors (4.3%) is underscored. In our setting however, cancer of the bladder accounts for 28.5% of all tumors whereas in the literature a higher frequency has been reported for lymphoma, lung, thyroid or renal cell cancer. A review of the literature has revealed significant differences in frequency and tumor type reported in patients on long-term dialysis. A two-stage diagnostic protocol to detect bladder tumors in patients on dialysis is described. During diagnostic work up, we attempt not to be aggressive in these patients. Due to the high incidence of bladder tumors, we believe that at least the first stage of this diagnostic protocol should be performed in all patients that are symptomatic or require urologic work up prior to inclusion in a kidney transplant program. We report our experience in 14 cases diagnosed as having tumors in a series of 324 patients on dialysis. PMID- 2200353 TI - [Neurogenic bladder caused by meningomyelocele in childhood: urodynamic pattern and treatment regimens]. AB - The authors reviewed the records of 160 patients with neurogenic bladder secondary to myelomeningocele (MMC) treated at the Urology Department of the University of Padua during 1977-1988. All patients had been evaluated by excretory urography, urethrocystography and videocystomannometry (VCM). Urodynamic studies are fundamental in determining vesicosphincteric dysfunction and patients who are at high risk for early renal lesions. For this reason, the authors recommend urodynamic evaluation from the first year of the infant's life in order to institute treatment early. The therapeutic approach should aim at a) preserving renal function, b) achieving a socially acceptable degree of urinary continence, and c) protecting sexual function. PMID- 2200354 TI - [Paratesticular rhabdomyosarcoma]. AB - We report a case of paratesticular rhabdomyosarcoma in a 5-year-old boy who was submitted to radical orchidectomy via the inguinal approach and high ligation of the spermatic cord. Clinical and retroperitoneal staging classify this case under group I of the Intergroup Rhabdomyoma Study. Adjuvan chemotherapy with 12 courses of VAC have achieved a good clinical course to date (14 months after surgery) and a good outcome is predicted. We review the literature and discuss the features of this mesenchymal tumor. PMID- 2200355 TI - [Spontaneous nephrocutaneous fistula. Report of a case and review of the literature]. AB - A case of right-sided spontaneous nephrocutaneous fistula in a 69-year-old female patient is reported. She had previously undergone surgery for ureteral lithiasis on the same side. The radiologic and surgical findings are described and the probable etiopathogenesis of this condition are discussed. PMID- 2200356 TI - Agalactosyl IgG, antibodies to heat shock proteins, and acute rheumatic fever. AB - In rheumatoid arthritis an increased proportion of the N-linked oligosaccharides on serum IgG terminate with N-acetylglucosamine (agalactosyl IgG). It has recently been shown that group A streptococcal cell wall peptidoglycan/polysaccharide complex may be used to raise monoclonal antibodies which bind to this glycoform of IgG. Patients with rheumatoid arthritis also have increased levels of antibody to the 65 kD and 70 kD families of heat shock proteins, particularly to a bacterial (Mycobacterium bovis) homologue of heat shock protein hsp65. Streptococci must contain similar heat shock proteins. Acute rheumatic fever follows infection with group A streptococci, and these organisms might theoretically evoke antibody to heat shock proteins or changes in the levels of agalactosyl IgG, which is antigenically cross reactive with their cell walls. It is shown here that serum samples from patients with acute rheumatic fever do not differ from those from normal children by these criteria. PMID- 2200357 TI - Subchondral avascular necrosis: a common cause of arthritis. AB - (1) Subchondral avascular necrosis is an important cause of joint pain and disability and accounts for upwards of 20% of total hip replacements done in our hospital. (2) Early diagnosis may be made with the aid of magnetic resonance imaging and radioactive isotope studies. (3) Although the signs and symptoms are similar to those of osteoarthritis, there are significant differences--namely, (a) a history of sudden onset of pain, present in more than half the patients; (b) a younger age group; (c) a shorter duration of symptoms at time of surgery; (d) clinically the limiting factor is pain rather than actual joint deformity to account for restriction of movement; (e) a high incidence of multiple sites of involvement. (4) The disease is commonly associated with steroid treatment or alcohol abuse. Although many other causes are recognised, they are rare in Western urban practice. (5) Patients with stage I-II subchondral avascular necrosis, especially of the knee, are better treated conservatively. (6) Surgical treatment gives less satisfactory results than the treatment of osteoarthritis by similar modalities. PMID- 2200358 TI - Hepatitis and non-steroidal anti-inflammatory drugs. PMID- 2200360 TI - Seroepidemiological studies on five outbreaks of trichinellosis in southern Spain. AB - Five outbreaks of trichinellosis, involving 86 people, took place in Andalucia (Southern Spain) between 1984 and 1987. Four of them were caused by eating infected pork and one by eating wild boar meat. The human sera were analysed by the immunofluorescence assay test, which showed circulating anti-Trichinella antibody titres of up to 1:10240. A micro-ELISA test, carried out with sera from two of the outbreaks, revealed the presence of circulating antigens 68 and 78 days after infection. Finally, 11 of 17 samples of products prepared with pork and wild boar meat showed Trichinella larvae after acid-pepsin digestion. The close geographical localization of three of the outbreaks suggests that the southwestern corner of Spain is an endemic focus of trichinellosis. PMID- 2200359 TI - Raised plasma renin and prorenin in rheumatoid vasculitis. AB - The value of plasma renin and its inactive precursor, prorenin, were examined as a marker for vasculitis in rheumatoid arthritis (RA). Plasma renin and prorenin rise when the renin-angiotensin system is activated; an isolated increase of prorenin may be a marker for microvascular complications in diabetes mellitus. Renin concentrations in plasma obtained from 34 patients with RA (seven with vasculitis, 27 controls) were measured under standard conditions, before and five days after stopping non-steroidal anti-inflammatory drugs; creatinine clearance was also measured. At first the median renin concentration in the patients with vasculitis was 19 (range 12-63) mU/l (normal less than 61 mU/l) and in the controls 9 (3-43) mU/l. The median prorenin concentration in patients with vasculitis was 233 (144-428) mU/l (normal less than 358 mU/l) and in the controls 144 (25-364) mU/l. Renin and prorenin concentrations increased significantly in both groups after withdrawal of nonsteroidal anti-inflammatory drugs. The creatinine clearance was similar in both groups and did not correlate with renin concentrations. In conclusion, it was found that, unlike patients with diabetes mellitus, patients with RA with vasculitis had slightly raised concentrations of both renin and prorenin. These findings signal activation of the renin angiotensin system and might indicate early cardiac or renal involvement by vasculitis. PMID- 2200361 TI - Immunoglobulin G-dependent classical complement pathway activation in neutrophil mediated cytotoxicity to infective larvae of Angiostrongylus cantonensis. AB - The participation of antibody and complement in cell-mediated adherence and cytotoxicity to infected larvae (L3) of Angiostrongylus cantonensis was investigated in vitro. Of the different cell types involved in the reaction, neutrophils were seen to have a predominant role in immune serum--dependent adherence and cytotoxicity to L3. In the presence of immune serum, cytotoxicity to L3 by neutrophils from infected rats was twice that of neutrophils from normal rats. Although mononuclear cells and eosinophils from infected rats significantly increased the adherence to L3, they had little lethal effect on L3. A further study using gel filtration (Sephacryl S-200) and affinity chromatography (protein A) revealed that immunoglobulin G (IgG) alone was responsible for the complement activation in neutrophil-mediated killing of L3. Neither adherence nor cytotoxicity to L3 by neutrophils were affected when immune serum was heated to 50 degrees C or treated with zymosan, but they were markedly decreased when immune serum was treated with Mg2(+)-ethylene glycol-bis-(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid. The results of this study indicate that the neutrophil-mediated adherence and cytotoxicity to L3 of A. cantonensis are mediated through IgG-dependent classical complement pathway activation. PMID- 2200362 TI - Clostridium botulinum in the soil of Kenya. PMID- 2200364 TI - Paraplegia associated with the use of oxidized cellulose in posterolateral thoracotomy incisions. AB - Three patients suffered permanent neurologic injury after oxidized regenerated cellulose migrated into the spinal canal after thoracotomy. These cases are reported to alert surgeons of this potential complication when oxidized cellulose is used to achieve hemostasis in the posterior angle of the thoracotomy incision. PMID- 2200363 TI - Paraplegia associated with thoracotomy. PMID- 2200365 TI - Hemostatic technique for internal mammary artery anastomotic bleeding. AB - When internal mammary artery is used for myocardial revascularization, a not uncommon occurrence is intraoperative bleeding from the internal mammary artery to coronary artery anastomosis. The conventional method of hemostasis of placing additional sutures across the suture line may produce anastomotic stenosis or may aggravate the bleeding by producing tears, especially as these additional sutures are placed on a beating heart. We describe a simple technique by which hemostasis can be achieved without the risk of anastomotic stenosis or aggravation of the bleeding, as it avoids placing sutures over the anastomotic suture line. PMID- 2200366 TI - Use of the allograft aortic valved conduit. PMID- 2200367 TI - Paradoxical hypertension after repair of coarctation of the aorta: a review of its causes. AB - Correction of a coarctation of the aorta, an apparent simple cause of hypertension, paradoxically can provoke two hypertensive responses, one of which is potentially fatal. The first, limited to the first 24 hours, occurs in nearly one half of the patients. This is likely due to the high set of the carotid baroreceptors. The second, which may be associated with abdominal pain and, in some, with necrosis of the small bowel as a result of severe arteritis confined to arteries arising from the aorta below the coarctation, develops in about one half of the first responders. Norepinephrine excretion greatly increases for several days, whereas angiotensin levels are elevated for 3 to 4 days. The hypertension responds to beta-blockers, to arterial smooth muscle relaxants, and to angiotensin converting enzymes. A theory is advanced to explain the second response. It is the adaptation gone awry that ensures adequate flow to exercising muscles below the coarctation, above and beyond that delivered by increasing the systolic pressure. It could be a regionally controlled mechanism similar to the rationing of blood flow in diving mammals. PMID- 2200368 TI - Closed chest cardiac massage. PMID- 2200369 TI - [Effect of the producer type on the nature of antibiotic fermentation]. AB - Fermentation processes in production of bacitracin, a polypeptide antibiotic by Bacillus licheniformis, and oleandomycin, a macrolide antibiotic by Streptomyces antibioticus, were studied comparatively. It was shown that the antibiotic producing actinomycete was characterized by a prolonged phase of growth retardation. The highest efficiency of the control actions was observed at the beginning of the fermentation. They were aimed at intensifying the substrate usage during the growth phase and activation of cell metabolism. Controlled cultivation of the Bacillus representative was based on its capacity of achieving the maximum growth rate possible under the certain conditions. Therefore, an increase in the quantity of the synthesized antibiotic was due, under such conditions, to inhibition of the culture growth by various means including lower mass exchange intensity. PMID- 2200370 TI - [Analysis of plasmid profile of antibiotic-resistant Enterobacteriaceae circulating in hospitals]. AB - Certain pheno- and genotype properties of S. typhimurium and some other representatives of Enterobacteriaceae resistant to antimicrobial drugs were studied. The strains were isolated from children with salmonellosis within 4 months when an infection hospital was subjected to microbiological observation. It was shown that by their antibiotic resistance, phagovars and molecular weights of the plasmid DNas, the strains S. typhimurium were similar to those isolated during hospital infections. The conjugative plasmids responsible for antibiotic resistance in some strains did not differ in their molecular weights and antibiotic resistance markers. The strains S. typhimurium similar in their pheno- and genotype properties were isolated only from 2 patients which allowed one to consider it possible that the patients were infected by the strains of common genesis. Analysis of nonpathogenic representatives of Enterobacteriaceae isolated from the patients along with the S. typhimurium strains confirmed the fact that the patients were infected with the same pathogenic strain. PMID- 2200371 TI - [Microbiological control of drug resistance of causative agents in suppurative septic infections in newborn infants]. AB - Resistance of the main causative agents of purulent septic infections such as pneumonia, meningitis, sepsis, etc. to 11 chemotherapeutic drugs was studied. The pathogens were isolated from autopsies of 203 newborns who died within 1981 to 1987. Among 2978 isolates belonging to Enterobacteriaceae (2466 strains) and Pseudomonadaceae (512 strains) which constituted 88% of all the isolates, strains with multiple resistance predominated: 90% of the strains resistant to 4 or more antibiotics, 77% of the strains resistant to 6 or more antibiotics and 48% of the strains resistant to 8 or more antibiotics. The highest number of the isolates were resistant to 8 and 9 chemotherapeutics (19 and 20%, respectively). 84% of all the isolates belonged to 4 genera: Klebsiella (34%), Escherichia (21%), Serratia (14%) and Pseudomonas (15%). They were characterized by the highest resistance spectra. In all the cases massive colonization of the intestine by the strains with multiple resistance which caused purulent septic infections was observed. The most frequent variants of the drug resistance combination were determined. In the total frequency of the isolate with multiple resistance no significant differences were detected in 1981 and thereafter. In 1986-1987 the frequency of S. marcescens strains increased 3-5 times with simultaneous broadening of their drug resistance spectra. Strains of S. marcescens and K. pneumoniae with multiple drug resistance endemic for definite hospitals were detected. PMID- 2200372 TI - [Cyclosporin biosynthesis and dynamics of bioenergetic processes in cyclosporin producing strain]. AB - An attempt was made to show a correlation between definite bioenergetic parameters of the cells of the cyclosporine-producing culture and biosynthesis of cyclosporine. It was found that the three strains producing cyclosporine used in the study had an alternative cyanide-resistant pathway along with the classical cytochrome chain. In the strain forming only traces of the cyclopeptide during fermentation of the cyanide-resistant respiration constituted 60 to 80%. In the isogenic highly productive strains the cyanide-resistant respiration appeared to be markedly decreased beginning from the 1st day of fermentation and during the maximum biosynthesis of cyclosporine (on day 4 or 5 of fermentation) it reached zero. The ATP content in the cells of the highly productive strain, despite its decrease by the antibiotic biosynthesis peak, remained at a much higher level than that in the strain producing only traces of cyclosporine. A procedure for isolating functionally active mitochondria from the protoplasts was developed and a bioenergetic characterization of the mitochondria isolated from the strains with different antibiotic productions is presented. PMID- 2200373 TI - [Effects of a new derivative of 5-alkyl-3N-furanones on the colonization resistance of the intestine in albino mice]. AB - By its antagonistic function normal microflora provides the intestine with resistance to colonization with exogenic opportunistic and pathogenic microorganisms. The drug was effective in inducing a decrease in the intestine colonization resistance which in its turn leads to filling of free ecological niches with exogenic microflora. In this connection the suggestion that specification of a new chemical agent should include along with other criteria its effect on colonization resistance is valid. It was shown with the use of indicator microorganisms that when administered per os in doses of 40 and 80 mg/kg daily for 3 and 6 days, respectively, a new original compound 1929, a derivative of 5-alkyl-3H-furanones, with high antimicrobial activity induced no significant or more pronounced changes in the colonization resistance of the gastrointestinal tract of noninbred albino mice than furagin used as the reference drug. PMID- 2200374 TI - [Stability of plasmids and competition of plasmid-containing and plasmid-free strains during continuous cultivation]. PMID- 2200375 TI - [Biological properties of aromatic, heterocyclic and aliphatic omega-amino acids]. PMID- 2200376 TI - Norman Cousins' sick laughter redux. PMID- 2200377 TI - Antipyresis and fever. AB - While understanding of the mechanisms of fever has progressed in recent years, much uncertainty remains as to whether fever in itself (as distinct from its cause) is beneficial or harmful, and what circumstances warrant antipyretic therapy. This review was designed to identify studies providing information on the effects of fever and of pharmacologic and physical therapy. Fever or analogous behavioral thermal upregulation apparently has positive effects on defense against infection in some animal models. Retrospective studies in humans suggest that failure to mount a febrile response is associated with poor outcome in certain infections but do not establish a causal relationship. Induction of fever apparently had therapeutic value in infections such as syphilis before specific antimicrobials were developed. Fever may have deleterious effects in the context of borderline cardiovascular or neurologic function or pregnancy, but data in most instances cannot separate effects of fever per se from that of underlying disease. Antipyretic drugs are effective in diminishing fever, but they have significant side effects and may suppress signs of ongoing infection. Physical cooling is important when physiologic thermoregulatory mechanisms are overwhelmed, but may sometimes increase discomfort and metabolic stress in fever. Antipyretic therapy should not be instituted routinely for every febrile episode but should be based on evaluation of relative risks in the individual case and reassessed if anticipated benefits are not achieved. PMID- 2200378 TI - Atrial fibrillation. Thromboembolic risk and indications for anticoagulation. AB - The risk of embolic stroke in patients with atrial fibrillation is largely related to the underlying disorders responsible for the arrhythmia. Atrial fibrillation associated with rheumatic mitral valve disease has the highest stroke risk (about 17 times greater than unaffected controls), but even with nonvalvular heart disease, the risk is increased fivefold. The stroke risk is greater with chronic than with paroxysmal atrial fibrillation, is highest in the year after onset of the arrhythmia, and is lower in younger patients with idiopathic ("lone") atrial fibrillation. Major bleeding episodes, the most important risk of anticoagulation, occur in about 5% to 10% of patients. The decision to anticoagulate a patient with atrial fibrillation depends on the cause of the arrhythmia, especially any associated cardiovascular disease, and the individual's risk from anticoagulation. Growing evidence supports the effectiveness of anticoagulation of most patients with nonvalvular, as well as valvular, cardiac disease for the prevention of both primary and recurrent strokes. PMID- 2200379 TI - Dyspnea. Pathophysiologic basis, clinical presentation, and management. PMID- 2200380 TI - A randomized trial to improve self-management practices of adults with asthma. AB - The prevalence and impact of adult asthma are substantial, and poor self management practices, especially failures to adhere to treatment regimens, appear to be a significant problem. Desirable characteristics of an intervention program to improve self-management were identified through needs assessment and review of existing patient education resources. A comprehensive program was developed that integrated a workbook with one-to-one counseling and adherence-enhancing strategies. A longitudinal 1-year study compared patients receiving this self management program with "usual care" patients receiving standard asthma pamphlets. Patients were randomly assigned to conditions. Baseline score and asthma severity were statistically controlled. Self-management patients had substantially better adherence than usual care patients, as well as improved functional status, at follow-up. Hospital and emergency department visits decreased in both groups but did not differ between groups. PMID- 2200381 TI - Effects of a rapid antigen test for group A streptococcal pharyngitis on physician prescribing and antibiotic costs. AB - Decision analysis and opinion survey suggest that introduction of rapid antigen detection tests should decrease the number of patients with negative test results for group A streptococcal pharyngitis treated by antibiotics. We reviewed all cases in which a test for group A streptococcal pharyngitis was performed during the last 7 months of culture diagnosis and the first 7 months of antigen test diagnosis at an inner city community health center, recording culture or antigen test results, whether antibiotics were prescribed, and patient status (as regular health center patients or patients referred to the center). Positive rates for culture and antigen-test periods were similar (10% and 12%), but 53% of patients with negative culture were treated, where only 32% of patients with negative antigen-test results received prescriptions. Significant reductions in the treatment of patients with negative test results were found in both patient status subpopulations: health center patients, 43% to 29%; referred patients, 91% to 52%. Among health center patients reductions were consistent for both adult (30% to 21%) and child and adolescent (55% to 45%) age groups. For all patients with negative test results, direct costs of diagnostic reagents and antibiotic prescriptions fell from $3.58 per patient with culture to $3.45 with antigen testing; the $0.13 savings per patient was due to less treatment of referred patients. Thus, rapid antigen testing led to (1) significantly fewer patients with negative test results receiving antibiotic prescriptions; and, (2) savings in antibiotic costs offsetting reagent cost of antigen detection diagnosis. PMID- 2200382 TI - A comparison of the efficacy and safety of a beta-blocker, a calcium channel blocker, and a converting enzyme inhibitor in hypertensive blacks. AB - A double-blind, positively controlled, forced dose titration study comparing the efficacy and safety of atenolol, captopril, and verapamil sustained release as single agents in the treatment of black patients with mild to moderate hypertension (diastolic blood pressure, 95 to 114 mm Hg) was conducted. A total of 394 patients were randomized to one of the three therapies. Mean blood pressures during a 2- to 4-week placebo treatment period (baseline) ranged from 100.4 to 100.7 mm Hg diastolic and 151.7 to 152.5 mm Hg systolic for the three groups. Of the patients, 355 (of whom 345 had assessable data) completed the first treatment period, which consisted of therapy with either 50 mg/d of atenolol, 25 mg every 12 hours of captopril, or 240 mg/d of verapamil sustained release. During the second 4-week treatment period, which 319 patients completed (307 assessable), half of the patients had their antihypertensive medication increased and the other half continued the same dose. Goal blood pressure was defined as a supine diastolic pressure of less than 90 mm Hg or a 10-mm Hg or greater drop in supine diastolic blood pressure from pretreatment levels. Atenolol, captopril, and verapamil sustained release therapy was associated with goal blood pressure achievement during the first treatment period 55.1%, 43.8%, and 65.2% of the time, respectively, and during the second treatment period 59.6%, 57.1%, and 73.0% of the time. Side effects were minimal and comparable for all three drugs. PMID- 2200383 TI - Diagnosis of group A beta-hemolytic Streptococcus using clinical scoring criteria, Directigen 1-2-3 group A streptococcal test, and culture. AB - Cultures for group A beta-hemolytic Streptococcus were performed on 806 patients presenting with a sore throat to five urgent care centers. The accuracies of a clinical scoring system and of a liposomal in-office direct test for Streptococcus were compared with culture results. The Directigen 1-2-3 group A streptococcal test had a sensitivity of 67%, a specificity of 85%, a positive predictive value of 61%, and a negative predictive value of 89% compared with culture. The scoring system had a sensitivity of 26%, a specificity of 94%, a positive predictive value of 58%, and a negative predictive value of 79%. Using a combination of the direct test results and the clinical score did not improve the accuracy significantly over the use of either alone. The rates of delayed treatment, unnecessary treatment, and increased costs were compared using different combinations of the clinical scoring system, the in-office streptococcal test, and culture. Neither the Directigen 1-2-3 group A streptococcal test nor the clinical score can replace culture in the diagnosis of group A beta-hemolytic streptococcal pharyngitis. PMID- 2200385 TI - Researches on antibacterial and antifungal agents, XII: Analogues of bifonazole with two imidazole moieties and related azoles. AB - Analogues of bifonazole bearing two imidazole rings and other related azoles have been synthesized and tested as antifungal agents against Candida albicans and Candida spp.. Only a slight part of the antifungal power of the parent drug is retained by some derivatives as evinced by the comparison of new compounds with bifonazole, miconazole, and ketoconazole. PMID- 2200384 TI - Hypertensive black men and women. Quality of life and effects of antihypertensive medications. Black Hypertension Quality of Life Multicenter Trial Group. AB - A multicenter, randomized double-blind clinical trial was conducted among 306 black men and women with mild to moderate hypertension to determine effects of atenolol, captopril, and verapamil SR on measures of quality of life. Patients were randomly assigned to a stable or forced-dose titration sequence. After an 8 week treatment period, the rate of withdrawal from treatment because of adverse effects was low and did not differ by drug treatment group or titration level. Patients taking verapamil SR showed a significantly greater reduction in mean blood pressures than patients treated with atenolol or captopril. Along with absence of worsening on any quality of life total scale scores examined over the treatment period, we found either improvement or no change in the total scale scores for all three treatment groups. Among both male and female patients, comparisons between drug treatment groups showed no differences in degree of change on the total scale scores. In comparisons within each treatment group, improvement in scores of male patients after 8 weeks appeared among those taking atenolol in general well-being and physical symptoms reduction; among male patients taking captopril in general well-being, physical symptoms, and sexual performance; and among male patients receiving verapamil SR in scores in irritability, sleep, and the Digit Span test. Improvement in scores among female patients taking atenolol was found in scores on general well-being, physical symptoms, and sleep; among women taking captopril on general well-being, physical symptoms, and irritability; and among women taking verapamil SR on general well being. Patients in all treatment groups improved on measures of visuomotor functioning. The research shows that with the three newer generation antihypertensive medications studied, blood pressure control was achieved during the treatment period without negative effects on quality of life scales, along with findings of improvement on some measures. Given the special clinical features of hypertension in black patients, the study underlines as well the potential and utility of systematic tracking of measures of quality of life, while monitoring blood pressures in this patient population. PMID- 2200386 TI - [Nutrition of the cat]. AB - The requirement of the cat in respect to protein, energy, vitamins and minerals are presented. The special requirements of this carnivore appear to be due to the loss or charge of certain metabolic processes which are normally present in species such as the dog. PMID- 2200387 TI - [Granulopoiesis]. PMID- 2200388 TI - Nodular posterior scleritis. PMID- 2200390 TI - Life-style studies in sociology: from typologies to fields and trajectories. PMID- 2200389 TI - [Sonographic diagnosis of early pregnancy in horses, cattle, sheep, goats, swine, dogs and cats. Standard values and limitations]. AB - Ultrasonography allows early and reliable pregnancy detection in several domestic animals. Transrectal sonography can be recommended in horses and cattle, transrectal or transcutaneous procedures in sheep, goats and pigs while transcutaneous ultrasound scanning is appropriate in dogs and cats. Three periods of time can be distinguished in the diagnosis of early pregnancy by ultrasound: the earliest phase, where signs of pregnancy can be found in some cases, but accuracy of diagnosis is very low; the succeeding period, where reliable diagnosis is possible, but results are often difficult to achieve and examination can be time consuming; the third phase in which ultrasound diagnosis is very accurate even under practice conditions and can be efficiently carried out on a large scale basis in breeding management. To achieve high accuracy in determining pregnancies a suitable ultrasound scanner with a good image quality and considerable expertise are required. Under field conditions ultrasonic pregnancy diagnosis should be possible: from Day 14 in the horse, from Day 25-28 in cattle, from Day 25 (transrectal), resp. 35 (transcutaneous) in sheep, goats and swine and from Day 24-25 (transcutaneous) in the dog and cat. Before this period of time reliable diagnosis is sometimes possible: between Day 11 and 13 in the horse, between Day 20 and 25 in cattle, between Day 20 and 25 (transrectal), resp. between Day 30 and 35 (transcutaneous) in sheep and goats, between Day 20 and 25 (transrectal) and Day 22 and 35 (transcutaneous) in swine and between Day 19-20 and 24-25 in the dog and cat. Earlier sonographic indications of pregnancy are not sufficiently reliable for large scale accurate pregnancy diagnosis. PMID- 2200392 TI - Psychological aspects of launching new products. PMID- 2200391 TI - The role of attitudes and preferences in food choice. PMID- 2200393 TI - Trends in the choice of food and indicators of differences in consumption styles. PMID- 2200395 TI - Dieting and life-style. PMID- 2200394 TI - Health and vegetarian life-style. PMID- 2200396 TI - Food choice in modern society. PMID- 2200397 TI - Mediterranean meal patterns. PMID- 2200398 TI - Finnish meal patterns. PMID- 2200399 TI - European trends in conviviality and eating out. PMID- 2200400 TI - Rapid mapping of deletion and duplication mutations by the polymerase chain reaction. PMID- 2200401 TI - Distribution and molecular form of immunoreactive big endothelin-1 in porcine tissue. AB - In the present study a specific and sensitive radioimmunoassay for big endothelin 1 was developed. Half maximal inhibition of binding of radioiodinated big endothelin-1 was observed at 58 pg/tube and big endothelin-1 was detectable as low as 2 pg/tube. With this assay, the regional distribution of big endothelin-1 was determined in porcine tissue and compared to the distribution of an immunoreactive endothelin. Considerable amount of immunoreactive big endothelin-1 was observed in the aortic intima (0.84 +/- 0.094 pg/mg wet tissue; mean +/- S.D.) and the lung (0.47 +/- 0.055), but there was a low concentration in other tissue including the kidney inner medulla, which has been shown to be abundant in immunoreactive endothelin. Furthermore the molecular form of immunoreactive big endothelin-1 in aortic intima was found to be big ET-1[1-39], but the molecular form of major immunoreactive big endothelin-1 in the lung is big endothelin-1[22 39] with big endothelin-1[1-39] being minor. PMID- 2200402 TI - Increased tyrosine phosphorylation in ras transformed fibroblasts occurs prior to manifestation of the transformed phenotype. AB - Murine fibroblasts transformed by ras oncogenes exhibited an increased amount of tyrosine phosphorylated proteins compared to normal cells. The pattern of phosphorylation was similar to that observed in cells chronically stimulated with EGF or PDGF, and is probably due to autocrine stimulation of receptor tyrosine kinases. NIH 3T3 cells transfected with H-ras under the control of a glucocorticoid inducible promoter were used to determine the temporal relationship among expression of p21H-ras oncoprotein, increase in tyrosine phosphorylation and appearance of the transformed morphology. Enhanced tyrosine phosphorylation was observed more than 24 hours before evidence of morphological changes. These results suggest that full transformation by ras oncogenes requires cooperation with tyrosine protein kinases. PMID- 2200403 TI - Rapid release of endothelin and ATP from isolated aortic endothelial cells exposed to increased flow. AB - Freshly harvested rabbit aortic endothelial cells on filters were exposed to two 3 min periods of a sixfold increase in flow rate of the perfusion buffer. This led to an increase in the levels of endothelin and ATP in the perfusate; arginine vasopressin remained at the basal level. Less ATP was released on the second exposure to high flow; however, endothelin release was not diminished. Using immunohistochemical techniques, endothelin and arginine vasopressin were localised in the same population of endothelial cells; endothelin and vasopressin were present in approximately 90% and 70% of endothelial cells, respectively, which suggests that there is some co-localisation. This is the first time that a stimulation has been shown to produce rapid release of endothelin. PMID- 2200404 TI - Co-purification of proteases with basic fibroblast growth factor (FGF). AB - Acidic and basic fibroblast growth factors (FGFs) are proteins of 16-18 kDa. Other forms of 25-30 kDa related to this growth factor family have recently been described. All these components bind tightly to heparin-Sepharose, a property that allows the purification of several FGF-related proteins. During the purification of acidic and basic FGFs from bovine pituitary glands, we detected the presence of 28-30 kDa components that are immunoreactive against anti-basic FGF antisera. However, microsequencing analysis revealed that the 28-30 kDa components are lysosomal proteases that co-elute with basic FGF from heparin Sepharose columns. The involvement of these proteases in the etiology of microheterogenous forms of FGFs and/or release of FGFs from the extracellular matrix is discussed. PMID- 2200405 TI - Raising high density lipoprotein cholesterol. The biochemical pharmacology of reverse cholesterol transport. PMID- 2200406 TI - Relevance of ionic effects on norfloxacin uptake by Escherichia coli. AB - The uptake of the quinolone drug norfloxacin by Escherichia coli was investigated at initial rate kinetics at different pH and monovalent/divalent metal ion concentration. The results support a simple diffusion mechanism for quinolone incorporation into cells. The uptake process decreases under acidic conditions. The presence of Na+ or K+ ions does not affect the results to an appreciable extent, whereas divalent ions cause a dramatic decrease in drug incorporation. The antibacterial activity, evaluated under identical experimental conditions, shows a direct relationship with the uptake data. As a general explanation for the above results it is suggested that the ability of the drug to penetrate into cells is a function of its net charge. The molecule in the zwitterionic form exhibits maximum permeation properties, whereas the uptake is remarkably reduced when the drug bears a net charge as a result of ionization or complex formation with bivalent ions. These results allow further insight into the mechanism of quinolone access to the intracellular compartment. PMID- 2200407 TI - Stimulation and inhibition of 1,3-bis(2-chloroethyl)-1-nitrosourea-induced strand breaks and interstrand cross-linking in Col E1 plasmid deoxyribonucleic acid by polyamines and inorganic cations. AB - The influence of various polyamines and metallic cations on 1,3-bis(2 chloroethyl)-1-nitrosourea (BCNU)-induced DNA single-strand breaks and DNA interstrand cross-linking was in Col E1 plasmid using electrophoretic techniques. Spermidine and spermine (0.4 to 1.5 mM concentration range) markedly stimulated BCNU-induced DNA nicking, whereas putrescine had no effect on the nicking process. In contrast to the polyamines, BCNU-induced DNA nicking was decreased by the three inorganic cations, Na+ (100 and 200 mM), Mg2+ (0.5 and 1.5 mM), and Co3+ (NH3)6 (0.2 and 0.4 mM), with the trivalent hexamminecobalt ions being most inhibitory. When the monofunctional N-methyl-N-nitrosourea (MNU) was used (instead of the bifunctionally active BCNU) to alkylate Col E1 DNA, nicking of the DNA was inhibited by spermidine. Furthermore, the ability of chloroethylated Col E1 DNA to form interstrand cross-links after treatment with BCU was inhibited by 0.5 mM spermidine and 0.5 mM spermine, both concentrations within the intracellular range. Putrescine at 3-6 mM only marginally stimulated DNA cross linking. In comparison, the inorganic cations all enhanced Col E1 DNA cross linking by BCNU, with the rank order of cross-link stimulation being Mg2+, Na+, and Co3+ (NH3)6. These results provide evidence that polyamines can interact with DNA to modulate chloroethylnitrosourea-induced DNA damage and that the interaction is not only a function of the charge on the polyamine molecule but also of the chemical structure of the polyamine. PMID- 2200408 TI - Kidney sialidase and sialyltransferase activities in spontaneously and experimentally diabetic rats. Influence of insulin and sorbinil treatments. AB - Kidney cortex sialic acid level, sialidase and sialyltransferase activities have been measured in spontaneously diabetic BB rats and in streptozotocin-diabetic rats (STZ). In untreated diabetic BB rats, at the onset of the disease, sialidase specific activity was found to be increased by 21% when compared with diabetes resistant BB controls (P less than 0.05) whereas sialyltransferase activity was not significantly modified and bound sialic acid concentration was diminished (P less than 0.05). In diabetic BB rats submitted to a minimal insulin therapy, during 3 months of disease, sialidase activity and sialic acid concentration were similar to those of Wistar age-matched controls. In STZ-diabetic Wistar rats, sialidase specific activity was increased by 76% after 5 months of disease when compared to age-matched Wistar controls (P less than 0.01); in contrast, specific sialyltransferase activity was decreased by 21% (P less than 0.05); these enzymatic alterations were associated with a decrease in bound sialic acid concentration (P less than 0.01); 1 month's insulin therapy, started 4 months after onset of the disease, normalized sialidase activity but had no effect on sialyltransferase activity and sialic acid concentration; treatment with sorbinil prevented cataract development but had no effect on sialidase activity whereas it emphasized the decrease in sialyltransferase activity and sialic acid concentration. The disturbances in the enzyme activities concerned with sialoglycoconjugate metabolism observed in experimental and spontaneous diabetes may be responsible for the decreased bound sialic acid content observed in the rat kidney cortex. PMID- 2200409 TI - Immunochemical quantitation of 3-(cystein-S-yl)acetaminophen protein adducts in subcellular liver fractions following a hepatotoxic dose of acetaminophen. AB - The hepatotoxicity of acetaminophen correlates with the formation of 3-(cystein-S yl)acetaminophen protein adducts. Using a sensitive and specific immunochemical assay, we quantitated the formation of these protein adducts in liver fractions and serum after administration of a hepatotoxic dose of acetaminophen (400 mg/kg) to B6C3F1 mice. Adducts in the cytosolic fraction increased to 3.6 nmol/mg protein at 2 hr and then decreased to 1.1 nmol/mg protein by 8 hr. Concomitant with the decrease in adducts in the cytosol, 3-(cystein-S-yl)acetaminophen protein adducts appeared in serum and their levels paralleled increases in serum alanine aminotransferase. Microsomal protein adducts peaked at 1 hr (0.7 nmol/mg protein) and subsequently decreased to 0.2 nmol/mg at 8 hr. The 4000 g pellet (nuclei, plasma membranes, and cell debris) had the highest level of adducts (3.5 nmol/mg protein), which remained constant from 1 to 8 hr. Evaluation of fractions purified from a 960 g pellet indicated that the highest concentration of 3 (cystein-S-yl)acetaminophen protein adducts was located in plasma membranes and mitochondria; peak levels were 10.3 and 5.1 nmol/mg respectively. 3-(Cystein-S yl)acetaminophen protein adducts were detected in nuclei only after enzymatic hydrolysis of the proteins. The localization of high levels of 3-(cystein-S yl)acetaminophen protein adducts in plasma membranes and mitochondria may play a critical role in acetaminophen toxicity. PMID- 2200410 TI - Antimalarial activity of a 4',5'-unsaturated 5'-fluoroadenosine mechanism-based inhibitor of S-adenosyl-L-homocysteine hydrolase. AB - A 4',5'-unsaturated 5'-fluoroadenosine inhibitor of S-adenosyl-L-homocysteine hydrolase (SAH hydrolase; EC 3.3.1.1), MDL 28842, was found to inhibit markedly the growth of Plasmodium falciparum in vitro and Plasmodium berghei in mice. Inhibition of P. berghei growth was associated with a large increase in the concentration of S-adenosyl-L-homocysteine (SAH) in the erythrocytes of the mice treated with MDL 28842. This increase in SAH was due apparently to inhibition of the mouse erythrocyte SAH hydrolase activity, because SAH hydrolase activity was undetectable in either P. berghei or P. falciparum isolated from infected erythrocytes, although enzyme activity was readily detected in mouse erythrocyte extracts. Therefore, MDL 28842 probably inhibits plasmodial growth indirectly by adversely changing the milieu of the host erythrocyte. SAH hydrolase represents a worthwhile target for the future development of potent inhibitors for the chemotherapy of malaria. PMID- 2200411 TI - [Metabolic consequences of muscle fatigue]. PMID- 2200412 TI - Vagal and sympathetic control of gastric and duodenal bicarbonate secretion. AB - This report summarizes data concerning the extrinsic neural control of bicarbonate secretion by the gastric and duodenal mucosa. Parasympathetic vagal effects have been studied in experimental animals and in man by means of direct electrical vagal stimulation, sham-feeding procedures and intracerebroventricular peptide injections. The results show that the vagal nerves have a stimulatory effect on gastroduodenal bicarbonate secretion. Furthermore, both conventional nicotinic and muscarinic cholinoceptor, as well as non-cholinergic transmission, mediate the vagal effect. Sympathetic splanchnic nerve effects have been investigated by means of nerve sections, direct electrical stimulation, reflex activation and stereotaxic electrical hypothalamic stimulation. The data show that the splanchnic nerves have a predominantly inhibitory action on gastroduodenal bicarbonate secretion by use of peripheral adrenergic neurones and receptors of the alpha-2 subtype. The role of the adrenal glands is not fully understood. It is concluded that gastroduodenal bicarbonate secretion is under autonomic neural control, mainly in the classical antagonistic fashion; the parasympathetic vagal nerves stimulate bicarbonate output, whereas the sympathetic splanchnic nerves are mainly inhibitory. PMID- 2200413 TI - Pathophysiology of gastrointestinal mucosal permeability. AB - The intestinal mucosa is composed of multiple barriers to the lumen-to-blood transport of solutes, including the unstirred water and mucous layers, the apical and basolateral cell membranes of the epithelial cell, the paracellular junctions, the interstitial matrix, and the capillary and lymphatic endothelia. The epithelial barrier appears effectively to restrict the movement of solutes with a radius as low as 3 A, yet it also permits limited permeation by molecules as large as albumin (36 A radius). There is evidence to suggest that the restrictive properties of the gastrointestinal mucosa are significantly altered under various physiological and pathological conditions, and measurement of plasma (or luminal) clearances of water-soluble molecules has proved to be a popular method for studying intestinal permeability. The aim of this review is to discuss the concept of the plasma clearance method, methodological aspects of the technique, factors that influence plasma-to-lumen clearance measurements (e.g. solute size, blood flow, and permeability of the epithelial cell barrier), and advantages and disadvantages of the clearance method. Finally, application of the clearance technique to the study of ischaemia/reperfusion-, ethanol-, and FMLP induced mucosal injury will be described. PMID- 2200414 TI - New drug treatment for diarrhoea. AB - This paper reviews the scientific background to the development of new drugs for the treatment of diarrhoeal diseases, and it includes an update of three classes of drugs which may prove useful; gut specific alpha2-adrenergic agonists, intestinal Cl- channel blockers, and somatostatin analogues. PMID- 2200415 TI - Secretin-dependent HCO3- secretion from pancreas and liver. AB - Ultrastructural studies performed on pigs revealed that numerous cytoplasmic tubulovesicles were present in resting pancreatic duct cells. Elevation of systemic arterial PCO2 from 5.5 to 11 kPa increased the number of vesicles more than twofold. Following secretin administration, concurrent with the onset of HCO3- secretion (JHCO3), the cytoplasm became devoid of vesicles, and the basolateral plasma membrane surface area more than doubled. Similar phenomena were observed in bile duct cells. After pretreatment with the microtubules inhibiting drug colchicine, secretin failed to reduce duct cell vesicle density, and JHCO3 was reduced by c. 50% compared to the control. These ultrastructural changes resemble those described in other H+/HCO3(-)-transporting organs such as the distal nephron and the urinary bladder. Our findings are compatible with the notion that cytoplasmic vesicles containing H(+)-ATPases are incorporated into the basolateral plasma membrane of secretory cells during secretin stimulation. Active transport of H+ into interstitial fluid might therefore be the driving force underlying JHCO3. PMID- 2200416 TI - Leakage of HCO3- and mucosal restitution. AB - When the integrity of the gastric mucosa is destroyed, there is a large passive diffusion of interstitial HCO3- from the nutrient side to the luminal side of the tissue. In the absence of nutrient HCO3-, rapid repair of superficial mucosal injuries is slowed markedly down or does not take place at all. The effects of a high degree of luminal acidification, which prevents rapid repair, can be counteracted by high concentrations of nutrient HCO3-. The importance of nutrient HCO3- is emphasized by the finding that luminal acid may destroy both the fibrin network beneath which restitution occurs and the basal lamina along which viable cells must migrate to re-establish epithelial continuity. At the present time, it is not known whether the preventive effects of HCO3- against ulceration in a variety of systems are dependent upon leakage of HCO3- toward the surface, or whether nutrient HCO3- actually enters cells in order to regulate intracellular pH. PMID- 2200417 TI - Gastric mucosal acid-base balance. AB - Acute gastric ulceration induced by haemorrhagic shock is associated with profound intramucosal acidification due to diffusion of luminal H+ into the mucosa. High-HCO3- metabolic alkalosis protects the mucosa against this ulceration, whereas low-HCO3- respiratory alkalosis does not, suggesting that lack of systemic and intramucosal HCO3-, rather than tissue acidosis per se, renders the mucosa susceptible to ulceration. In normal mucosa, disruption of the mucosal barrier by taurocholate, ethanol or acetylsalicylic acid leads to efflux of alkali (HCO3-) from the mucosa, with generation of an alkaline buffer layer at the epithelial surface to protect the mucosa from further damage. In ischaemic mucosa no such protective alkaline layer is formed, and exposure to luminal acid leads to severe acidification of and damage to the mucosa. The efflux of alkali may be driven by capillary hydrostatic pressure, since no such protective alkaline efflux occurs in vitro, but rather exposure to luminal acid and barrier breaking agents results in intracellular acidification. The potential pathogenetic role of a disrupted intramucosal acid-base balance, as well as the protective effect of systemic and intramucosal HCO3- in acute gastric stress ulceration is further substantiated by the in vitro findings that perfusion conditions simulating in vivo ulcerogenic conditions provoke intracellular acidosis, and serosal HCO3- significantly contributes to the maintenance of normal intracellular pH in surface epithelial cells exposed to luminal acid. PMID- 2200418 TI - The adherent gastric mucus gel barrier in man and changes in peptic ulceration. AB - The mucus barrier is a layer of water-insoluble gel adherent to the gastroduodenal epithelium. In man most previous studies have focused on luminal mucus or histological assessment of presecreted, intracellular mucus--neither of which can be directly correlated with the protective capacity of the adherent mucus barrier. We here describe direct observation of adherent mucus thickness in man, and changes in peptic ulceration. Adherent mucus gel on human antral mucosa is a continuous homogeneous layer of variable thickness, in the range 50-450 microns (median 180 microns), comprising 67% polymeric mucin. In gastric ulcer patients, adherent antral mucus is significantly increased in thickness (median 240 microns), but is very heterogeneous and structurally a substantially weaker gel, comprising only 35% polymeric mucin. Adherent antral mucus from duodenal ulcer patients is homogeneous, significantly thinner (median 110 microns), and structurally a weaker gel, comprising 50% polymeric mucin. The adherent mucus layer from patients with gastric carcinoma resembled that from subjects with gastric ulcer in that it was very heterogeneous, of significantly increased thickness (median 240 microns) and structurally a very weak gel (23% polymeric mucin). These results are discussed in the context of gastroduodenal mucosal protection against acid and pepsin in the gastric juice. PMID- 2200419 TI - [Determination of the activity of alanine aminotransferase]. AB - Methods currently recommended by French, European and International Societies for determining the catalytic concentration of Alanine Aminotransferase (ALT) are reported. These methods are very close, recommend the apoenzyme reactivation by pyridoxal phosphate and allow the transferability of the results from site to site. Complementary information concerning commercial kits, adaptation to enzyme analyzers, specimen collection and storage, reference values and biological variations in healthy subjects are also given. The adoption of these homogeneous methods should make easier the choice of a cutoff value for ALT among blood donors for the prevention of posttransfusion hepatitis. PMID- 2200420 TI - Development of medical education in China. PMID- 2200421 TI - New heterocyclic derivatives of benzimidazole with germicidal activity--VII--2 (5'-nitro-2'-furyl or 2'-thienyl) benzimidazoles with different substituents in the 5-position. AB - In continuation of our previous research, the synthesis of 13 2-(5'-nitro-2' furyl or 2'-thienyl) benzimidazoles with different substituents in 5 position is described. The new compounds were tested in vitro against 5 (Gram+) and 4 (Gram-) strains and a mycete Candida Albicans. All the derivatives showed a certain degree of antibacterial and antimycotic activity, which in some cases was fairly good. PMID- 2200422 TI - [The importance of the endogenous agent and environmental factor thiocyanate for nonspecific and specific resistance from the hygienic viewpoint]. AB - Thiocyanate (previous designation rhodanide, SCN-) is a physiological substance which is ubiquitously spread in the animate nature. As an essential constituent of cell it participates in important physiological resp. biochemical processes. From the hygienic and microbiological point of view the occurrence of SCN- as environmental factor, its alimentary significance and its vitalizing effect (stimulation of nonspecific and specific warding off, stimulation of proliferation, protective effect at toxic loading) are of interest for the fundamental and applied research. PMID- 2200423 TI - Phenotypic properties of Klebsiella pneumoniae and K. oxytoca isolated from different sources. AB - 474 Klebsiella pneumoniae and K. oxytoca strains isolated from different sources (human clinical material, feces of healthy subjects, sewage) were investigated for phenotypic properties. Characteristics analyzed were cultural activities, antimicrobial susceptibilities and capsule types. Comparison of both species revealed differences in adonitol fermentation and resistance to tetracycline, nalidixic and pipemidic acid. Capsule types 2, 7 and 33 were frequently found in K. pneumoniae, but not in K. oxytoca. On the other hand, K 66 was common in K. oxytoca, but not in K. pneumoniae. With regard to the source of isolation, clinical strains of both species proved to be more resistant to mezlocillin, azlocillin and cephalothin than fecal and sewage strains. Similarly, resistances of K. pneumoniae to cotrimoxazole, nalidixic and pipemidic acid were most frequent in clinical strains. Multiple drug resistances were found most often in clinical isolates. Biochemically, different frequencies of positive reactions for urease, lysine decarboxylase activity and acetoin production were found between the groups. Capsule typing demonstrated K2 and K7 in K. pneumoniae and K55 and K66 in K. oxytoca to be more common in clinical and fecal isolates than in sewage strains. While cultural characteristics did not allow discrimination of strains from different sources, capsule typing indicated clinical isolates to be more phenotypically related to strains from feces than to sewage isolates. PMID- 2200424 TI - Search for Campylobacter species in the public water supply of a large urban community. AB - A survey of the water distribution network of a large urban community was performed during a one year period. In addition to standard indicator bacteria, Campylobacter species were looked for after filtration of 500 ml water samples by enrichment of the original filter followed by subculture on a Skirrow's medium as well as a direct filtration procedure on a non selective agar. All steps were performed at 37 degrees C. Specimens collected at the springs (206), treatment stations (206) and at different points along the network (479) were tested. Fourteen strains of Campylobacter were isolated. They were cephalothin resistant and hippurate negative but they did not grow at 42 degrees C. None of them was part of the enteropathogenic Campylobacters. All except one were found in untreated water; in 11 cases among 13 tested, standard indicator bacteria were positive. We conclude that there is a low incidence of Campylobacter species in the water supply tested, that they are sensitive to chlorination and that testing standard indicator bacteria is an effective indicator for Campylobacter species. PMID- 2200425 TI - Importance of planned health education for burn injury prevention. AB - The planning of health education in the prevention of burn injuries is typically incomplete and not stated explicitly, while the evaluation is executed only partially or is altogether non-existent. This article presents a theoretical framework for planning and evaluating health education for those at risk for burns. Systematic planning consists of an assessment of the magnitude and severity of the problem, an analysis of the behavioural risk factors, a study of the determinants of the most risky modes of behaviour, the design of an optimal intervention, and the implementation of this intervention. The evaluation phase deals with the effects on these five levels (implementation, intervention, determinants, behaviour and injury risk). Some common pitfalls are mentioned and special attention is given to the study of determinants of behaviour and to the design of the intervention. Furthermore, the importance of pretesting health education material is underlined. There appears to be a strong need for further research on the aetiology of burn injury and the relevant determinants of behaviour, before effective prevention can be realized. PMID- 2200426 TI - Racemates and enantiomers in drug research and development--introductory remarks. PMID- 2200427 TI - Stereoselective synthesis and the polyene macrolide antibiotics. AB - The stereochemical complexity of roflamycoin and other polyene macrolide antibiotics presents a formidable challenge to the synthetic chemist, and the lack of obvious disconnections makes the retrosynthetic analysis very complex. The alternating (1, 3, 5, ...) polyol chain in roflamycoin is difficult to synthesize in part because there is no simple method to assemble these chains from smaller subunits. We have addressed this problem and developed a simple, convergent method for assembling alternating polyol chains. It is designed around a new class of 1,3-diol synthons: 6-alkyl-4-thiophenyl-1,3-dioxanes. These 1,3 diol synthons are readily available from either homoallylic alcohols or beta hydroxyesters, which are themselves readily prepared in optically pure form. Reduction of these synthons under the appropriate conditions gives configurationally stable alkyllithiums with either syn or anti stereochemistry. Reaction with electrophiles produces protected syn or anti-1,3-diols. PMID- 2200429 TI - Fluoxetine and its two enantiomers as selective serotonin uptake inhibitors. AB - The biochemical and pharmacological profiles of R,S-fluoxetine and its R and S enantiomers have been compared and reviewed. Both enantiomers exhibit profiles analogous to R,S-fluoxetine as inhibitors of serotonin uptake in vitro and in vivo with about equal potencies or a eudismic ratio near unity. PMID- 2200428 TI - Chromatographic methods for optical purity determination of drugs. AB - Current awareness of the different actions that may be exerted by the two enantiomers of a racemic drug has prompted an increasing interest in chromatographic methods to determine enantiomer composition on a small scale. Of particular interest in this respect is the possibility of using columns containing chiral stationary phases which directly separate the enantiomers. The intensive ongoing research in this field has led to a number of commercially available columns for both gas and liquid chromatography suitable for this purpose. Since most drugs are favourably determined by reversed-phase liquid chromatography, columns containing chiral stationary phases which can be operated in the same mode, are of particular interest. Some of the most recent achievements in this area are highlighted in this paper. PMID- 2200430 TI - Enantiomer-specific pharmacokinetics. PMID- 2200431 TI - Stereoselective metabolism of anti-inflammatory 2-arylpropionates. AB - 2-Arylpropionic acids (profens) are a major group of non-steroidal anti inflammatory drugs. These compounds exist in two enantiomeric forms due to the presence of an asymmetric carbon atom alpha to the carbonyl function. In vitro tests have shown that the anti-prostaglandin synthetase activity of profens resides almost exclusively in the (+)-(S)-enantiomers, yet all profens except naproxen are marketed as racemates. The profens exhibit enantioselective pharmacokinetics, the most intriguing aspect of which is their unidirectional chiral inversion from the (-)-(R)- to the (+)-(S)-enantiomer. Since the transformation goes from the inactive to the pharmacologically active form, the (R)-enantiomer can be considered as a prodrug of its (S)-antipode. The available evidence suggests that this reaction proceeds via the formation of the acyl-CoA thioester of the 2-arylpropionates. Hutt and Caldwell have reviewed the literature describing this unusual metabolic process. The purpose of this paper is to present more recent findings from in vivo and in vitro studies and to summarize actual knowledge concerning the mechanism of the metabolic chiral inversion of profens. PMID- 2200432 TI - The development of chiral drugs. AB - For many years, scientists in drug development have been blind to the 3 dimensional consequences of stereochemistry, mainly due to the problem of synthesis and analytical methodology. Now that new techniques are available for the resolution of racemic mixtures, there is an increasing pressure to only synthesise single enantiomers, and although guidelines on stereoisomers from the all regulatory agencies are awaited, there is already sufficient information to suggest that developmental studies on racemates will be greatly increased. There is often stereospecificity in pharmacology and toxicology, but this is frequently not the case for pharmacokinetics where enantiomeric differences may only play a relatively small contribution to overall drug activity, except for some exceptions (NSAI). Other chiral developments are discussed, for example, dextro fenfluramine from rac-fenfluramine, together with the ideas of what may be required for their registration. PMID- 2200433 TI - Peripheral dopamine in essential hypertension. An early defense against hypertension failing during its progression? AB - Measurements of dopamine (DA) and its metabolites in plasma (DA sulfate) and urine (homovanillic acid) as well as its urinary response to furosemide revealed two distinct patterns: a hyperdopaminergic state in borderline essential hypertension (EH) and a renal DA deficiency in stable EH. Long-term follow-up demonstrated that despite treatment, approximately 20% of borderline hypertensive patients became stable hypertensive within 12 years. Preliminary data on reinvestigation of these patients indicated that their dopaminergic indices also changed from those typical of borderline hypertension to those characteristic of stable hypertension, a finding compatible with the hypothesis that the hyperdopaminergic patterns in borderline hypertension represent an early antihypertensive defense response which progressively fails in patients who go on to develop stable hypertension. PMID- 2200434 TI - Regulation of urinary dopamine by protein and NaCl. A model of extraneuronal amine formation in kidney. AB - Dopamine (DA) excretion correlates directly with NaCl intake, but in salt sensitive hypertensive subjects the DA response to NaCl is deficient. While the linkage between dietary NaCl and renal DA formation in normal or pathophysiological states is currently undefined, a model of renal amine production is proposed in which alterations in renal blood flow and/or renal tubular transport mechanisms account for both the normal and abnormal responses to dietary NaCl. This model derives, in part, from observations in experimental animals and in human subjects in which renal DA production is more highly correlated with renal serotonin (5-HT) formation than with indices of either sympathetic nervous system or adrenal medullary activity. PMID- 2200435 TI - Autoradiographic localization of vascular dopamine receptors. AB - By using combined in vitro radioreceptor binding and autoradiographic techniques, the pharmacological profile and the anatomical localization of dopamine-1 (DA-1) and dopamine-2 (DA-2) receptors were assessed in rat cerebral, mesenteric and renal arteries. 3H-SCH 23390 (DA-1 ligand) was bound by the medial layer of cerebral, mesenteric and renal arteries without different density in large, medium and small sized arteries. Moreover, 3H-SCH 23390 binding sites were not sensitive to chemical sympathectomy, suggesting postjunctional localization of DA 1 receptors. 3H-Spiroperidol (DA-2 ligand) was bound primarily by the adventitial, the adventitial-medial border as well as by the intimal layer of cerebral, mesenteric and renal arteries. The accumulation of adventitial and adventitial-medial 3H-spiroperidol binding sites was higher in medium and small sized arteries than in large ones and was remarkably reduced after chemical sympathectomy. These results show prejunctional localization of DA-2 receptors and further suggest that some DA-2 binding sites are located in the arterial intima. PMID- 2200436 TI - Functional effects of proximal tubular dopamine production. AB - Significant proximal tubular responses to exogenous dopamine require 0.1 to 10 mumol/L concentrations but endogenous peritubular dopamine and DOPA concentrations are in the picomolar to nanomolar range. Dopamine concentration approaches micromolar levels within proximal tubular cells and their brush borders, as a result of DOPA decarboxylation and secretion, and in collecting duct fluid, as a result of tubular fluid absorption. Thus dopamine probably acts either within the proximal tubule cell or brush border or from the collecting tubular lumen. DOPA and Na+ uptake are coupled; dopamine uptake is linked to intracellular electrical potential and its secretion to H+ counter-transport; therefore alterations in proximal tubular Na+ and H+ transport influence dopamine excretion. Haloperidol and SCH 23390 block dopamine excretion, therefore dopamine antagonists may inhibit tubular dopamine responses by lowering intracellular dopamine concentration as well as by receptor blockade. Evidence for an intracellular site of dopamine action can be deduced from the inhibitory effect of DOPA on oxygen consumption and 86Rb uptake in proximal tubule cells. We have confirmed these findings in isolated proximal tubule cells but not in proximal tubule fragments. The discrepant responses may be due to the fact that isolated cells loose their polarity while tubule fragments remain polarized. Dopamine inhibition of proximal tubular Na+, K(+)-ATPase is not reproduced by single dopamine agonists or inhibited by dopamine antagonists. Dopamine effects which are not linked to known dopamine receptors may be the result of redox cycling. Micromolar dopamine oxidizes sulfhydryl groups which may modify enzyme structure and activate protein kinase C. PMID- 2200437 TI - Dopamine and natriuresis. Mechanism of action and developmental aspects. AB - The present paper summarizes our studies on the mechanisms of the dopamine induced changes in renal macro- and microcirculation as well as in proximal and distal tubular sodium handling which contributes to the natriuresis induced by the drug. Some aspects of the physiological role of locally generated dopamine in regulating sodium excretion are also reviewed. Finally, by describing the cardiovascular, renal and hormonal effects of dopamine in the preterm human neonate, some of the developmental aspects of the renal effects of the drug are also discussed. PMID- 2200439 TI - Research in physical medicine and rehabilitation. IX. Primary data analysis. AB - The primary statistical analysis is approached from the standpoint of what is required to publish in medical research journals. Descriptive and bivariate statistics cover the majority of medical research articles now published. Statistical guidelines for review of manuscripts are used to develop guidelines for analysis, including specifying the objective, the source of subjects and response rate, differences detectable with the expected sample size, appropriateness of statistics for one and two variables, method of presentation of results and conclusions and calculation of confidence intervals. Common mistakes to avoid include use of standard error of the mean instead of standard deviation, use of standard deviation with skewed data, failure to describe the statistical test used, multiple comparisons and failure to use special forms of t test and chi 2. PMID- 2200438 TI - Role of endogenous dopamine in the natriuresis accompanying various sodium challenges. AB - The contribution of endogenous dopamine (DA) to the natriuresis accompanying various sodium challenges is reviewed. Data are presented suggesting that DA participates in the control of sodium excretion produced by a normal sodium diet, increments in sodium consumption, and an acute infusion of isoosmotic saline. In contrast, the natriuresis accompanying a high sodium diet in the dog and extracellular fluid volume expansion with hypoosmotic saline or a very large volume of isoosmotic saline is independent of DA activity. Thus, the evidence suggests that DA contributes to the natriuresis produced by some, but not all, forms of sodium loading. PMID- 2200440 TI - Revision mastoidectomy. AB - The objectives of modern otologic surgery are elimination of disease and restoration of hearing. Persistent drainage and recurrent infection after mastoid surgery hallmark failure at achieving these goals. Medical management consisting of meticulous aural toilette and attention to accompanying medical disorders will often yield resolution; however, a significant number of patients will still require surgical revision. While intact canal wall procedures have reduced the chronic difficulties associated with open cavities, they are prone to failure. Careful assessment of the disease process and development of a surgical approach that is both flexible and complete will maximize success in revision surgery. Disease persistence after revision should be considered in the spectrum of complications, even though at times it is nearly impossible to avoid. We describe the reasons for failure of mastoid procedures, common areas of retained disease, and review key concepts of revision. PMID- 2200441 TI - The efficacy of absorbable suture for microvascular anastomoses. AB - Although microvascular anastomoses are routinely performed with nonabsorbable sutures, a foreign body reaction can be stimulated that acts as a nidus for inflammation, infection, and possible thrombosis. Absorbable sutures should be able to diminish this reaction. There are sparse data describing the use of absorbable sutures for both arterial and venous anastomoses. This investigation compares standard microvascular anastomotic technique using nonabsorbable 10-0 sutures (nylon) with absorbable 10-0 sutures (polyglactin 910), using a previously reported tubed superficial epigastric flap model in rats. Patency rates and histologic responses are compared at intervals of 3 days and 1, 2, 8 and 12 weeks postoperatively. Arterial and venous patency rates were similar for both materials (overall nonabsorbable, 85.9%; overall absorbable, 84.4%). A somewhat increased inflammatory response was noted in the arterial absorbable group at 1 week and in both the venous and arterial nonabsorbable groups at 8 and 12 weeks postoperatively. The later finding most probably represents the continued presence of the nylon sutures. The incidence of intraluminal thrombosis was greater for nonabsorbable suture, occurring in two arterial and four venous anastomoses, compared with only one absorbable suture venous anastomosis. We conclude that nonabsorbable suture is as efficacious as standard absorbable material in both arterial and venous microanastomoses with the potential benefit of diminished foreign body reaction. PMID- 2200442 TI - Ultrastructural changes with age in the human superior laryngeal nerve. AB - Electron-microscopic morphometric techniques were used to examine age-related changes in postmortem human superior laryngeal nerves obtained at autopsy (young adult, aged 20 to 30 years; old, 60 years and over). A statistically significant age-related loss of myelinated nerve fibers was detected (old, 7032 +/- 1572; young, 10,179 +/- 1969), representing a 31% decrease. Much of this loss occurred selectively in small myelinated fibers (1 to 2 microns) where there was an extensive (67%) and significant age-related fiber loss. A corresponding analysis of axonal diameter of myelinated nerve fibers similarly showed an extensive (67%) and statistically significant decrease in myelinated fibers with small axonal diameters (0 to 0.5 microns) in the old age group compared with the young adult age group. These findings may represent a significant histomorphologic correlate to the observed age-related sensorimotor dysfunction of the upper aerodigestive tract common in the elderly. PMID- 2200443 TI - Spontaneous trigeminal-facial reinnervation. AB - Although spontaneous recovery of denervated facial muscles has been anecdotally recorded in the clinical setting, it has never been fully documented. The establishment of anastomoses between the terminal trigeminal and facial nerves provides a possible explanation of this phenomenon. Mechanisms of myoneurotization have also been described, by which regenerating branches of severed peripheral motor nerves directly reach motor end plates of denervated muscles, with variable recovery of function. A case demonstrating unequivocal clinical evidence of trigeminal-facial cross-innervation is presented, and the pertinent literature is reviewed as it applies to the mechanisms of this phenomenon. PMID- 2200444 TI - Poorly differentiated ('insular') thyroid carcinoma. Report of two cases and review of the literature. AB - The clinical, histopathologic, immunohistochemical, and electron microscopic findings of two cases of poorly differentiated ("insular") thyroid carcinoma are reported and compared with the 25 cases previously described in the literature. These 27 cases occurred in eight men and 19 women, aged from 34 to 77 years. All but 2 presented with a thyroid mass. Eleven (41%) of the 27 patients experienced local recurrences following surgery, 17 (63%) had development of cervical lymph node metastases, 5 (19%) had development of mediastinal lymph node metastases, 11 (41%) had pulmonary metastases, and 9 (33%) had bone metastases, and 9 (33%) had bone metastases. At least 15 patients (56%) are known to have died of their disease, usually within 8 years of diagnosis. Pathologically, the tumors are distinctive and grow as solid islands (insulae) of small cells separated by artifactually created clefts. In some instances, small follicles are also noted within the insulae. All tumors were positive on immunostaining for thyroglobulin. In view of the propensity for local recurrences and lymphatic and hematogenous dissemination, a total thyroidectomy and neck dissection would seem advisable. Additionally, adjuvant external beam irradiation, systemic chemotherapy, and/or radioactive iodine therapy should also be considered. PMID- 2200445 TI - Treatment of severe bronchomalacia with expanding endobronchial stents. AB - Respiratory compromise from tracheobronchomalacia in children varies from mild to severe, but can result in either reflex apnea or death. Such severe cases may be unresponsive to aggressive medical management, and surgical options must be considered. Current surgical alternatives are limited and are associated with many potentially undesirable complications. Failure rates are often high. We present two infants with profound life-threatening airway malacia treated by endoscopic placement of a self-expanding endobronchial stent. A description of their anomaly, surgical management, and long-term care is included. The expandable stent may obviate the need for complex high-risk surgical procedures and prolonged ventilatory support. PMID- 2200446 TI - Culture, ELISA and immunofluorescence tests for the diagnosis of conjunctivitis caused by Chlamydia trachomatis in neonates and adults. AB - The relative value of culture, direct specimen antigen detection tests, i.e., enzyme-linked immunosorbent assay (ELISA) and immunofluorescence (IF) tests in the diagnosis of Chlamydia trachomatis infection was studied in 125 newborns and 121 adults with signs of conjunctivitis. Eye and nasopharyngeal samples were tested by culture using cycloheximide-treated or irradiated McCoy cells, ELISA (i.e., Chlamydiazyme, Abbott) and IF tests (i.e., Chlamyset, Orion and MicroTrak, Syva). Of the neonates, 70 (35 boys and 35 girls) and 54 (33 males and 21 females) of the adults were positive in one or both eyes in one or more tests: 191 (39%) in cultures, 173 (35%) in ELISA and 160 (33%), 176 (36%) in each of the IF tests. Using culture as standard reference, the sensitivities of ELISA and the IF tests were 88%, 81% and 87%, while the corresponding specificities were 99%, 98% and 97%, respectively. The predictive values for a negative test (PVN) were 93%, 89% and 92% and for a positive test (PVP) 98%, 96% and 94%. Of the 124 cases chlamydia-positive in the eyes, 67 (54%), 76 (61%), 64 (52%) and 70 (57%) were positive in nasopharyngeal samples in one or more of culture, ELISA and the two IF tests, respectively. The sensitivities of ELISA and the IF tests in nasopharyngeal samples were 87%, 78% and 81%, while the corresponding specificities were 90%, 93% and 91%, respectively. The predictive values for a negative (PVN) test were 95%, 92% and 93%, and for a positive test (PVP) 76%, 81%, and 77%. Nasopharyngeal swabs were more often positive in cases with 2 or more weeks' duration of symptoms than in those with shorter duration. PMID- 2200447 TI - Differentiation signals in the CNS: type-2 astrocyte development in vitro as a model system. PMID- 2200448 TI - Identification and localization of ryanodine binding proteins in the avian central nervous system. AB - Ryanodine binding proteins of the CNS have been identified using monoclonal antibodies against avian skeletal muscle ryanodine binding proteins. These proteins were localized to intracellular membranes of the dendrites, perikarya, and axons of cerebellar Purkinje neurons using laser confocal microscopy and immunoelectron microscopy. Ryanodine binding proteins were not found in dendritic spines. Immunoprecipitation and [3H]epiryanodine binding experiments revealed that the cerebellar ryanodine binding proteins have a native molecular weight of approximately 2000 kd and are composed of two high molecular weight (approximately 500 kd) polypeptide subunits. A comparable protein having a single high molecular weight polypeptide subunit was observed in the remainder of the brain. If the ryanodine binding proteins in muscle and nerve are similar in function, then the neuronal proteins may participate in the release of calcium from intracellular stores that are mechanistically and spatially distinct from those gated by inositol trisphosphate receptors. PMID- 2200449 TI - Neurite outgrowth in response to transfected N-CAM changes during development and is modulated by polysialic acid. AB - We have used monolayers of control 3T3 cells and 3T3 cells transfected with a cDNA encoding human N-CAM as a culture substrate for embryonic chick retinal ganglion cells (RGCs). At embryonic day 6 (E6), but not at E11, RGCs extended longer neurites on monolayers of N-CAM-transfected cells. This loss of RGC responsiveness was not associated with substantial changes in the level of N-CAM expression on RGC growth cones. The neurite outgrowth response from E6 RGCs could be inhibited by removal of N-CAM from the monolayer, by removal of alpha 2-8 linked polysialic acid from neuronal N-CAM, or by antibodies that bind exclusively to chick (neuronal) N-CAM. In contrast, the response was not dependent on neuronal beta 1 integrin function. These data provide substantive evidence for a homophilic binding mechanism directly mediating N-CAM-dependent neurite outgrowth, and suggest that changes in polysialic acid expression on neuronal N-CAM may modulate N-CAM-dependent axonal growth during development. PMID- 2200451 TI - Human acidic fibroblast growth factor overexpressed in insect cells is not secreted into the medium. AB - We have overexpressed human acidic fibroblast growth factor (aFGF) in Spodoptera frugiperda Sf9 cells from a cDNA clone under the control of the promoter of the polyhedrin gene of the baculovirus Autographa californica nuclear polyhedrosis virus. A 16.5-kD product was made in recombinant virus-infected cells that specifically reacted in immunoblots with various antibodies prepared against aFGF. Recombinant aFGF was mitogenic for BHK21 cells and its activity was stimulated by heparin. The mechanism of release of FGF from mammalian cells is unknown. Both acidic and basic FGF lack classical amino-terminal signal sequences for secretion, and they are very inefficiently released from cells. Sf9 cells infected with the recombinant virus produced 10-20 mg aFGF/10(9) cells, corresponding to about 10-20 pg/cell. Despite this high level of expression, only about 0.5 and 1.3% of the total aFGF was found in the culture medium at 48 and 72 hr postinfection, respectively. This indicates that aFGF is not actively secreted out of the cells either via the normal exocytic pathway or directly through the plasma membrane in this heterologous cell system. PMID- 2200450 TI - Functional expression of Shaker K+ channels in a baculovirus-infected insect cell line. AB - We constructed a recombinant baculovirus, A. californica nuclear polyhedrosis virus, containing the Drosophila Shaker H4 K+ channel cDNA under control of the polyhedrin promoter. When infected with this recombinant baculovirus, the cell line Sf9, derived from the army-worm caterpillar S. frugiperda, expresses fully functional Shaker transient K+ currents, as assayed by whole-cell recording. K+ currents begin to appear at about 15 hr after infection, and they continue to increase over the next 3 days. Over the same period of time, a 75 kd band appears on SDS gels stained with Coomassie blue. The identity of this band as a Shaker gene product is confirmed by Western blot analysis using an anti-Shaker antiserum. The 75 kd band accounts for a substantial fraction of the membrane protein in Shaker-infected Sf9 cells. These results give hope that the baculovirus system, which has been used successfully for high-level expression of soluble proteins from higher eukaryotes, may be appropriate for producing large amounts of cloned ion channel proteins as well. PMID- 2200452 TI - Physicochemical activation of recombinant latent transforming growth factor beta's 1, 2, and 3. AB - Native and recombinant forms of transforming growth factor-beta 1 (TGF-beta 1) are synthesized predominantly as biologically latent complexes. Physicochemical analysis demonstrates that the more recently described TGF-beta 2 and TGF-beta 3 are also latent, and reveals a common series of sharply defined parameters for activation. Human recombinant latent TGF-beta's 1 and 2 show identical profiles of activation by acid and base; the transition from latency occurs between pH 4.1 and 3.1, and between pH 11.0 and 11.9. The profile for chicken recombinant latent TGF-beta 3 is slightly shifted with activation between pH 3.1 and 2.5, and between pH 10.0 and 12.3. Thermal activation of native and recombinant latent TGF beta 1 occurs over the temperature ranges of 75-100 degrees C and 65-100 degrees C, respectively, with complete activation after 5 min at 80 degrees C. Temperatures above 90 degrees C result in thermal denaturation of TGF-beta 1 itself. Recombinant latent TGF-beta's 2 and 3 are also activated over this temperature range; however, maximum activation occurs at 100 degrees C. These results suggest common elements in latent complex structure despite differences between the TGF-beta subtypes in pro-region primary sequence. PMID- 2200453 TI - Beyond efficacy testing: introducing preventive cardiology into primary care. AB - The interventions of documented efficacy that have been developed for the treatment of cardiovascular disease risk factors have been neither rapidly nor completely incorporated into clinical practice. This may be due to not recognizing that there is a fundamental conflict between the attributes of the ideal protocol for testing the efficacy of an intervention and the attributes of ideal patient care. For example, when testing an intervention for efficacy, benefit to the subject must be made secondary to the goal of increasing the community's fund of knowledge. When caring for patients, increasing the community's fund of knowledge must be secondary to the goal of benefiting the patient who is receiving care. Therefore, the ideal efficacy-testing program is minimally responsive to the needs of the individual subject; the ideal treatment program is maximally responsive to the needs of the individual patient. A second reason for the slow incorporation of preventive cardiology into patient care is the current lack of a supporting structure. An understanding of the attributes of good patient care and the need for a structure to support preventive cardiology interventions should further the incorporation of preventive cardiology interventions into routine patient care while allowing patient care systems to be scrutinized with efficacy-testing protocols. PMID- 2200454 TI - Magnetic resonance imaging of the pulmonary arteries and veins. PMID- 2200455 TI - Magnetic resonance imaging of vascular rings. PMID- 2200456 TI - Magnetic resonance imaging of the aorta in children. PMID- 2200457 TI - Magnetic resonance imaging in the evaluation of postoperative congenital heart defects. PMID- 2200458 TI - Nutrition science from vitamins to molecular biology. AB - Nutrition is a science of great importance. Indeed, unless one studies it, one might be afraid to eat anything, in view of all the scare stories about food. Today is the age of molecular biology and above all of DNA. The human genome project will bring new understanding of genetic diseases, and many of these will be "inborn errors of metabolism," in which nutrition has an important role. The challenge of nutrition is to help provide a healthy diet for all the world. PMID- 2200459 TI - Amino acid metabolism in human cancer cachexia. AB - Cancer cachexia is a complex syndrome that occurs with variable incidence in patients with solid tumors and those with hematologic malignancies. It is associated with characteristic physical and laboratory findings, and at a more fundamental level, with significant abnormalities in carbohydrate, lipid, and protein metabolism. These alterations in intermediary metabolism are demonstrable early in the syndrome, even before the onset of weight loss, when the more characteristic features of cancer cachexia are evident. Progressive wasting of peripheral protein stores is a major feature of cancer cachexia and often one of the most graphic realities of malignancy for patients and their families. Unfortunately, significant problems with the animal models of cancer cachexia make conclusions derived from animal studies difficult to extrapolate to humans. Data from human studies indicate that human cancer cachexia is associated with minimal aberrations in circulating free amino acid concentrations; increased whole-body protein turnover, synthesis, and catabolism; reduced rates of skeletal muscle protein synthesis; and increased rates of hepatic protein synthesis. Whether or not these alterations represent pathologic responses or physiologic adaptation by the host to the presence of malignancy remains to be seen. Future investigations must focus on more careful evaluation of interorgan amino acid metabolism, investigation of skeletal muscle protein catabolic rates in cancer cachexia, and definition of the roles of altered hormonal and cytokine regulation of these processes. Such studies will more precisely define the level at which amino acid metabolism is altered significantly and, we hope, permit more specific therapeutic intervention designed to reverse the debilitating effects of cancer cachexia. PMID- 2200460 TI - Iron deficiency. PMID- 2200461 TI - Effects of N-3 fatty acids on lipid metabolism. PMID- 2200462 TI - Plasma lipid transfer activities. PMID- 2200463 TI - The role of vitamin D in bone and intestinal cell differentiation. PMID- 2200464 TI - Nutritional factors in cataract. AB - Age-related cataract is a condition characterized by multiple mechanisms and multiple risk factors. The mechanisms that bring about a loss in transparency include oxidation, osmotic stress, and chemical adduct formation. Risk factors for cataract include diabetes, radiation (ultraviolet B, x-ray), certain pharmaceutical substances, certain nutritional states, and possibly acute episodes of dehydration. Interaction occurs between and among mechanistic factors and risk factors. Thus nutrition must be considered as one part of a tapestry of intertwined events and responses. Certain experimental models for nutritional cataract have been useful for study of the cataractogenic process but are probably not important factors in the human disease. Little current evidence supports significant roles in human senile cataract for imbalances of tryptophan or other amino acids, deficiencies of calcium or selenium, or excessive intake of selenium. Overconsumption of galactose is likely to be hazardous only in subjects with genetic inability to metabolize this sugar. Vitamins with antioxidant potential (riboflavin, vitamin E, vitamin C, carotenoids) deserve further research scrutiny to ascertain their significance in cataract etiology. Excessive caloric intake needs to receive added emphasis as a factor contributing to cataract. Diabetes increases the likelihood of cataract three- to four-fold. Obesity, defined as more than 20% overweight, is considered a major risk factor for non-insulin-dependent, or type II, diabetes (69, 73). Weight control can be recommended as a prudent, safe, economic, and effective means of lowering risk probability for diabetes and the associated complication of cataract. PMID- 2200465 TI - Regulation of energy expenditure in aging humans. AB - A brief overview of the effects of aging on two components of energy expenditure, RMR and TEF, has been presented. Whereas the decline in RMR appears to be related primarily to the loss of muscle tissue, the reason for the lower TEF in older individuals is less clear. Evidence has been provided suggesting that physical activity influences RMR and TEF in younger and older individuals. The possibility is raised that regular physical activity will increase RMR and TEF in older individuals. The increase in resting energy expenditure (RMR and TEF), in addition to the direct energy cost of physical exercise, may help increase the total energy requirements in older individuals. The majority of studies support an increase in resting SNSA in older individuals. The level of physical activity and percentage of body fat may be two factors contributing to age-related alterations in resting sympathetic tone. Future studies should continue to examine the effects of physical activity and body composition on metabolic rate and SNSA in older individuals. PMID- 2200466 TI - The role of nutrition in neural tube defects. PMID- 2200467 TI - Lipoprotein assembly and secretion by hepatocytes. PMID- 2200468 TI - Vitamin E: antioxidant activity, biokinetics, and bioavailability. PMID- 2200469 TI - Appetite regulation by gut peptides. AB - A number of gastrointestinal hormones that are released from the gut in response to intraluminal food stuffs have been shown to play a role in producing satiety. Some of these hormones apparently activate ascending vagal fibers that send messages to the nucleus tractus solitarius, and perhaps from there messages are sent to the paraventricular nucleus of the hypothalamus. Not only do gastrointestinal hormones play a role in the termination of a meal but they also appear to modulate energy metabolism (at least in rodents) through the activation of brown adipose tissue. PMID- 2200471 TI - The application of compartmental analysis to research in nutrition. PMID- 2200470 TI - The role of calcium in osteoporosis. AB - Calcium requirements may vary throughout the lifespan. During the growth years and up to age 25-30, it is important to maximize dietary intake of calcium to maintain positive calcium balance and achieve peak bone mass, thereby possibly decreasing the risk of fracture when bone is subsequently lost. The RDA for age 10-25 is 1200 mg/day. Calcium intake need not be greater than 800 mg/day during the relatively short period of time between the end of bone building and the onset of bone loss (30 to 40 years old). Starting at age 40-45, both men and women lose bone slowly, but women lose bone more rapidly around the menopause and for about 10 years after. Intestinal calcium absorption and the ability to adapt to low calcium diets are impaired in many postmenopausal women and elderly persons owing to a suspected functional or absolute decrease in the ability of the kidney to produce 1,25(OH)2D3. The bones then become more and more a source of calcium to maintain critical extracellular fluid calcium levels. Available evidence suggests that the impairments of intestinal calcium absorption observed during the menopause and aging can be overcome only by inordinately large calcium intakes (1500 to 2500 mg/day). Since this amount is difficult to derive from the diet, can cause constipation, and may not prevent trabecular bone loss, it should not be used as a substitute for sex hormone replacement. Women taking estrogen replacement should be provided the RDA for calcium of 800 mg/day at a minimum. Those who cannot or will not take estrogen should be asked to ingest at least 1000 to 1500 mg/day of calcium to delay cortical bone loss and prevent secondary hyperparathyroidism. It should be emphasized that up to 2000 mg/day of calcium is safe in teenaged children and adults. Excessive dietary intake of protein and fiber may induce significant negative calcium balance and thus increase dietary calcium requirements. It is also possible that excessive intakes of phosphate could have a deleterious effect on calcium balance in populations whose need for calcium is great (e.g. growing children) or whose ability to produce 1,25(OH)2D3 is impaired (e.g. the elderly). Moderation in the intake of these nutrients is urged. Generally, the strongest risk factors for osteoporosis are uncontrollable (e.g. sex, age, and race) or less controllable (e.g. disease and medications). However, several factors such as diet, physical activity, cigarette smoking, and alcohol use are lifestyle related and can be modified to help reduce the risk of osteoporosis. PMID- 2200472 TI - Zinc deficiency and immune function. AB - Zn deficiency can have marked effects on virtually all components of the immune system. That these effects can be functionally significant is demonstrated by the increased susceptibility of Zn-deficient animals to a number of bacterial, viral, and parasitic challenges. In addition, strong epidemiological data support the belief that Zn deficiency is a major factor underlying immune dysfunction in select human populations. Despite recognition of the importance of Zn in the ontogeny and functioning of the immune system, the biochemical lesions underlying the effects of Zn deficiency on immune responsivity have not been well characterized. Future efforts to delineate the effects of Zn on the production, release, and action of cytokines will likely produce significant advances in our understanding of the influence of this element on the immune system. The recent observation that Zn may be critical for the activity and binding of protein kinase C in lymphocyte membranes suggests that another fruitful area of research will involve examination of the influence of Zn deficiency on lymphocyte membrane structure and function. Finally, the recent recognition that Zn may be a critical factor in the activation/inactivation of immunoregulatory genes provides us with yet another avenue of research. PMID- 2200473 TI - Essential fatty acids and polyunsaturated fatty acids: significance in cutaneous biology. PMID- 2200474 TI - Molecular biology of selenoproteins. PMID- 2200475 TI - Nutritional aspects of AIDS. PMID- 2200476 TI - Metallothionein and the trace minerals. PMID- 2200477 TI - Adaptation of the exocrine pancreas to diet. AB - Pancreatic adaptation represents dietary regulation of gene expression; dietary substrates alter the synthesis and mRNA levels of their respective digestive enzymes. The mechanisms whereby mRNA levels change are not understood, but they must be elucidated. Although the changes in synthesis of proteases, amylase, and lipase parallel the changes in their mRNA levels in response to respective substrates, the concomitant changes in the synthesis of the other enzymes can be discordant with mRNA levels. The evidence supports a pretranslational mechanism of the adaptation of proteases, amylase, and lipase to their respective substrates and suggests potential translational mechanisms of other enzymes in these adaptations. Changes in synthesis occur within hours after a dietary change, but whether mRNA levels also change so early is unknown. Rapid, adaptive changes may occur by a different mechanism from later adaptation, possibly by translational control or nuclear transport. The differential effects of acute and chronic caerulein administration support the possibility of multiple mechanisms of regulation by a single effector. The mediators of pancreatic adaptations have not yet been identified, except for adaptation to dietary protein. CCK appears to mediate protease adaptation through the feedback regulation of its release by dietary protein. Available evidence supports a role of insulin and glucose in the adaptation to carbohydrate and a role of secretin and ketones in the adaptation to dietary fat. Elucidation of the mediators of pancreatic adaptation to carbohydrate and fat and their mechanisms is needed. PMID- 2200478 TI - The influence of respiratory research on clinical progress. PMID- 2200479 TI - The adult respiratory distress syndrome: definition and prognosis, pathogenesis and treatment. PMID- 2200480 TI - The role of lung surfactant. PMID- 2200481 TI - Sleep apnoea and the upper airway. PMID- 2200482 TI - Factors influencing intrapulmonary airway calibre during anaesthesia. PMID- 2200483 TI - Respiratory mechanics in anaesthesia. PMID- 2200484 TI - Respiratory muscle fatigue: mechanisms, evaluation and therapy. PMID- 2200486 TI - Effects of anaesthetics on the pulmonary circulation. PMID- 2200485 TI - Effects of anaesthesia on respiration. PMID- 2200488 TI - Pulmonary infection in intensive care units. PMID- 2200487 TI - Pharmacokinetic and metabolic properties of lung. PMID- 2200490 TI - Hypertension in the elderly: a study of a combination of atenolol and nifedipine. AB - The antihypertensive effects and tolerability of a once-daily, fixed combination of atenolol 50 mg and nifedipine retard 20 mg ('Nif-Ten') were monitored in a 12 month open study in 30 elderly hypertensive patients, whose blood pressure was inadequately controlled after four weeks treatment with atenolol 50 mg once daily. Sitting (and standing) blood pressure and heart rate one to four hours after dosing were recorded at entry (191/95 mmHg) and at the end of the run-in period (186/93 mmHg). After one month's therapy with the fixed combination the mean sitting blood pressure fell to 169/89 mm Hg and was maintained at this level for the entire 12-month period of observation. During the study four patients complained of side effects on fixed combination therapy with one patient withdrawn due to flushes and hot sweats. One other patient suffered flushes and hot sweats and two patients complained of mild dizziness. There were no demonstrable effects of fixed combination therapy upon the biochemical parameters measured. We conclude that the fixed combination of atenolol plus nifedipine retard was well tolerated over a 12-month period in the group of elderly hypertensive patients studied. The combination appears to exert a greater antihypertensive effect than the beta-blocker monotherapy with no evidence of tachyphylaxis, although these findings require confirmation in a controlled trial. PMID- 2200489 TI - Magnetoencephalography in clinical epileptology and epilepsy research. AB - This article reviews the application of magnetoencephalography (MEG) in clinical epileptology and epilepsy research. MEG recordings of interictal as well as ictal epileptiform discharges helped to improve non-invasive localization of epileptic foci in patients with focal epilepsy. Several studies showed good agreement of the localizations obtained from MEG compared with those from invasive electrical recordings. Thus, MEG may become a potentially useful technique in the pre surgical evaluation of epilepsy patients. As evidenced from studying the penicillin focus in animals and spike propagation in humans, MEG also may contribute to further understand the basic mechanisms of epilepsy and thus may be useful in epilepsy research. Directions of future research include recording from a large number of channels covering a wide area of the head, long-term recording to study mechanisms involved in the transition of interictal to ictal state, and recording of slow magnetic field shifts associated with interictal and ictal epileptiform discharges. PMID- 2200491 TI - Cosmetic varicose vein ligation using interrupted transcutaneous circumsuture. PMID- 2200492 TI - Oral nimodipine and cerebral ischaemia following subarachnoid haemorrhage. PMID- 2200494 TI - Percolation and binding of monoclonal antibody BW494 to pancreatic carcinoma tissues during high dose immunotherapy and consequences for future therapy modalities. AB - The distribution of the monoclonal antibody (MAb) BW494 in human pancreatic carcinoma biopsies during high dose intravenous immunotherapy was investigated. Using immunohistochemical techniques combined with anti-idiotypic, endothelial cell-specific and bispecific MAbs, it was shown that 3 days after onset of immunotherapy, MAb BW494 was bivalently bound to tumour cells in some highly vascularised areas near capillaries. No binding was observed in other highly vascularised tumour cell areas although the epitope detected by MAb BW494 was present. In contrast to our expectation the majority of the tumour cells were not yet saturated by the antibody, probably due to diffusion barriers in the solid tumour tissue. PMID- 2200493 TI - Which urogenital infection remedy? PMID- 2200495 TI - Human monoclonal antibody Ha6D3, a candidate for treatment of leukaemia? In vitro reactivity of Ha6D3 with leukaemic cells and in vivo applications in a chimpanzee. AB - The human monoclonal antibody Ha6D3 of the IgM type was used to stain malignant lymphoma cells from peripheral blood in flow cytometry and from cryosections of lymph nodes using the immunoperoxidase technique. It was found to react with peripheral white blood cells of all 12 cases of leukaemia and with lymph node cells of seven out of 11 B cell lymphomas and with the one T cell lymphoma tested so far. For in vivo experiments a batch of 70 mg Ha6D3 was purified and 6 mg Ha6D3 was injected intravenously into a chimpanzee with time intervals of 10 months and 1 month. The side effects observed were shivering, some muscular spasms and variations in the heart frequency. A decrease of lymphocytes of more than 50% was documented by haematogram analysis. The flow cytometry data showed that the Ha6D3 antigen does not modulate. Even after three repeated injections applied in a time interval of several months no immune response to Ha6D3 could be detected in vivo or in vitro. Based on these data we suggest that Ha6D3 may become a candidate for the treatment of certain leukaemias in vivo. PMID- 2200496 TI - Immunohistochemical and immunocytochemical study of bladder carcinomas using the epithelium-specific, tumour-associated monoclonal antibodies HMFG1 and AUA1. AB - The antigenic expression of normal bladder epithelium and transitional carcinomas has been studied using the epithelium-specific, tumour-associated monoclonal antibodies HMFG1 and AUA1. Tissues from 79 cases of bladder carcinoma and 11 cases of non-neoplastic bladder tissues were stained with both the haematoxylin eosin (H/E) and the indirect two-stage immunoperoxidase methods using the monoclonal antibodies (MAbs) HMFG1 and AUA1 at a concentration of 25 micrograms ml-1. Positive and negative controls were also used. Moreover, 46 urine smears prepared after cytocentrifugation were stained with both the Papanicolaou and the indirect two-stage immunoperoxidase methods. The results showed that HMFG1 reacted with the majority of cases of grade III carcinomas and carcinomas in situ and with a subset only of low-grade (I and II) carcinomas. The pattern of staining showed the following characteristics: (1) the epithelial surface membrane stained both in normal bladder and bladder carcinomas (surface of the papillae), (2) a variant number of cancer cells, increasing with the degree of malignancy, showed membrane and/or cytoplasmic staining, (3) tumours of the same histological grade showed antigenic heterogeneity. The MAb AUA1 was not widely expressed. The immunocytochemical study confirmed the reaction of HMFG1 with a variant number of malignant urothelial cells exfoliated in urine. Their reaction with AUA1 was much more limited. The immunocytochemical staining seemed to be more sensitive in the detection of malignant cells in some cases which had been characterized as negative or suspicious for malignancy by the Papanicolaou examination. The intravesical treatment with chemotherapeutic agents did not seem to influence the antigenic expression of malignant urothelial cells. PMID- 2200498 TI - Immunohistochemical identification of CA125 and the F(ab')2 fragments of the murine monoclonal antibody OC125 in ovarian cancer tissue. AB - Benign and malignant tissue samples of 19 ovarian cancer patients who received an intravenous infusion of radiolabelled F(ab')2 fragments of OC125 were examined for expression of CA125 and the cellular location of the injected antibodies. CA125 could be detected by immunohistochemistry in 47 of 71 biopsies containing cancer cells, but not in 258 biopsies with benign tissue. F(ab')2 fragments were found in 34 of these 47 biopsies. The diffuse intracytoplasmic staining pattern seemed to indicate that the injected antibodies had crossed the membranes of the cancer cells. Since the antibody could not be detected in benign tissues, further applications of OC125 for diagnostic and therapeutic purposes seems to be justified. PMID- 2200497 TI - Functional aspects of glycoprotein N-linked oligosaccharide processing by human tumours. PMID- 2200499 TI - Tumour-associated upregulation of the IL-4 receptor complex. AB - In a previous study we have shown that monoclonal antibody MR6, which we believe recognizes a component of the human IL-4 receptor complex, binds to a wide variety of epithelial tumours. We have now used this reagent to carry out more detailed analysis of tumours of the breast. Our immunohistochemical data indicate that approximately 30% of these tumours show elevated expression of the molecule to which MR6 binds. In addition, three samples of lymphoma were all MR6-positive. Normal breast tissue from the same patients was either negative or weakly positive. Immunoprecipitation and Western blotting analysis with MR6 show that the molecule expressed on tumour cells is indistinguishable from that on normal tissues. It has an apparent molecular weight of 200 kD, but is highly sensitive to proteolysis yielding a molecule of 145 kD. These data raise the possibility that upregulation of the IL-4 receptor complex may be involved in tumourigenesis. In addition, since only a third of tumours are MR6-positive, the antibody may have potential in differential diagnosis. PMID- 2200500 TI - Magnetic resonance imaging of bone marrow: diagnostic value in diffuse hematologic disorders. AB - Magnetic resonance imaging (MRI) has value in characterizing normal and abnormal bone marrow because of its ability to distinguish fat from other tissues. Due to this advantage, hematologic disorders resulting in alterations of the normal cellular and fatty marrow distribution can be appreciated. In this article, the role of MRI in diffuse hematologic disorders is emphasized. At birth, almost all marrow is cellular, but by age 25, cellular marrow is restricted to the axial skeleton and proximal femoral and humeral metaphysis. The remainder is fatty, consisting of 80% fat, 15% water, and 5% protein. With increased need for hematopoiesis, reconversion from fatty to cellular marrow occurs in many diffuse disease states. Diffuse diseases that affect bone marrow production are divided into four categories representing conditions that affect the pluripotent hematopoietic stem cell. These include stem cell failure resulting in aplastic anemia, uncontrolled stem cell proliferation as exemplified by polycythemia vera, stem cell dysplasia such as sickle cell anemia, and malignant transformations or replacement. The MRI appearance of these disorders is discussed in this article. The use of spin-echo (SE) sequences is the most common approach to bone marrow imaging. With T1-weighted SE images, fatty marrow will appear bright and cellular marrow, with lower fat content, will exhibit a lower density signal. With T2 weighted SE pulse sequences, contrast between fatty marrow and cellular marrow decreases. Contrast between fatty and cellular marrow is enhanced with chemical shift imaging, including Dixon out-of-phase imaging, as emphasized in this article. MRI presents a more global view of the bone marrow than biopsy material and should provide a better understanding of diffuse hematologic disease progression and resolution. PMID- 2200501 TI - [Embryo protection legislation should prevent abuse]. PMID- 2200502 TI - [Pioneers of pediatric medicine. Hermann Emminghaus (1845-1904)]. PMID- 2200503 TI - [Pioneers of pediatric medicine. Karl Stolte (1881-1951)]. PMID- 2200504 TI - [Pioneers in pediatric medicine. William Eduard Ladd (1880-1967)]. PMID- 2200505 TI - Growth, body composition, hormonal and metabolic status in lambs treated long term with growth hormone. AB - The effect of long-term (10 weeks) treatment with growth hormone (GH) was investigated in twin lambs, one sibling being a control and the other treated with GH (0.1 mg/kg live weight per d). The lambs were fed on a concentrate-grass cube (9:1 w/w) diet at a daily rate of 40 g fresh weight/kg live weight. The average daily live-weight gain of the GH-treated lambs was 36% greater than that of the controls (307 v. 225 g/d, P less than 0.01). The carcass composition of the GH-treated lambs changed: fat content was decreased (P less than 0.01) and protein content was increased (P less than 0.05) when expressed relative to carcass dry matter. The absolute weights and the weights when expressed relative to fleece-free empty body of some muscles were significantly increased in GH treated lambs. The mean retention times of both particulate- and liquid-phase components of the digesta were unchanged by GH treatment, when calculated for the rumen or for the entire gastrointestinal tract. The feed conversion ratio was significantly greater (P less than 0.01) in GH-treated lambs compared with controls. Nitrogen retained per g N intake was also significantly increased (P less than 0.05) by GH treatment. Plasma urea concentrations were decreased (P less than 0.05) and glucose concentrations were increased (P less than 0.01) in GH-treated lambs, whereas non-esterified fatty acid concentrations were unchanged. Plasma insulin and total insulin-like growth factor-1 concentrations progressively increased in GH-treated lambs as treatment time continued. They were significantly correlated after week 4 of treatment. Two types of hepatic GH binding site were detected, with high and low affinities for GH. The capacities of both binding sites were significantly increased (P less than 0.05) in GH treated lambs when expressed per unit microsomal protein but, when expressed per liver, only the capacity of the high-affinity site was increased. PMID- 2200506 TI - Structure of the ATP synthase complex (ECF1F0) of Escherichia coli from cryoelectron microscopy. AB - The structural relationship of the catalytic portion (ECF1) of the Escherichia coli F1F0 ATP synthase (ECF1F0) to the intact, membrane-bound complex has been determined by cryoelectron microscopy and image analysis of single, unordered particles. ECF1F0, reconstituted into membrane structures, has been preserved and examined in its native state in a layer of amorphous ice. Side views of the ECF1F0 show the same elongated bilobed and trilobed projection of the ECF1 views shown previously to be normal to the hexagonal projection. The elongated aqueous cavity of the ECF1 is perpendicular to the membrane bilayer profile in the bilobed view. ECF1 is separated from the membrane-embedded F0 by a narrow stalk approximately 40 A long and approximately 25-30 A thick. The F0 part extends from the lipid bilayer by approximately 10 A on the side facing the ECF1. There is no clear extension of the protein on the opposite side of the membrane. PMID- 2200507 TI - Single protein omission reconstitution studies of tetracycline binding to the 30S subunit of Escherichia coli ribosomes. AB - In previous work we showed that on photolysis of Escherichia coli ribosomes in the presence of [3H]tetracycline (TC) the major protein labeled is S7, and we presented strong evidence that such labeling takes place from a high-affinity site related to the inhibitory action of TC [Goldman, R. A., Hasan, T., Hall, C. C., Strycharz, W. A., & Cooperman, B. S. (1983) Biochemistry 22, 359-368]. In this work we use single protein omission reconstitution (SPORE) experiments to identify those proteins that are important for high-affinity TC binding to the 30S subunit, as measured by both cosedimentation and filter binding assays. With respect to both sedimentation coefficients and relative Phe-tRNAPhe binding, the properties of the SPORE particles we obtain parallel very closely those measured earlier [Nomura, M., Mizushima, S., Ozaki, M., Traub, P., & Lowry, C. V. (1969) Cold Spring Harbor Symp. Quant. Biol. 34, 49-61], with the exception of the SPORE particle lacking S13. A total of five proteins, S3, S7, S8, S14, and S19, are shown to be important for TC binding, with the largest effects seen on omission of proteins S7 and S14. Determination of the protein compositions of the corresponding SPORE particles demonstrates that the observed effects are, for the most part, directly attributable to the omission of the given protein rather than reflecting an indirect effect of omitting one protein on the uptake of another. A large body of evidence supports the notion that four of these proteins, S3, S7, S14, and S19, are included, along with 16S rRNA bases 920-1396, in one of the major domains of the 30S subunit. PMID- 2200508 TI - Zinc coordination, function, and structure of zinc enzymes and other proteins. PMID- 2200509 TI - Primary structure of the thermostable formyltetrahydrofolate synthetase from Clostridium thermoaceticum. AB - The complete nucleotide sequence of the Clostridium thermoaceticum formyltetrahydrofolate synthetase (FTHFS) was determined and the primary structure of the protein predicted. The gene was 1680 nucleotides long, encoding a protein of 559 amino acid residues with a calculated subunit molecular weight of 59,983. The initiation codon was UUG, with a probable ribosome binding site 11 bases upstream. A putative ATP binding domain was identified. Two Cys residues likely to be involved in subunit aggregation were tentatively identified. No characterization of the tetrahydrofolate (THF) binding domain was possible on the basis of the sequence. A high level of amino acid sequence conservation between the C. thermoaceticum FTHFS and the published sequences of C. acidiurici FTHFS and the FTHFS domains of the Saccharomyces cerevisiae C1-THF synthases was found. Of the 556 residues shared between the two clostridial sequences, 66.4% are identical. If conservative substitutions are allowed, this percentage rises to 75%. Over 47% of the residues shared between the C. thermoaceticum FTHFS and the yeast C1-THF synthases are identical, 57.4% if conservative substitutions are allowed. Hydrophobicity profiles of the C. acidiurici and C. thermoaceticum enzymes were very similar and did not support the idea that large hydrophobic domains play an important role in thermostabilizing the C. thermoaceticum FTHFS. PMID- 2200510 TI - Excited-state properties of Escherichia coli DNA photolyase in the picosecond to millisecond time scale. AB - Escherichia coli DNA photolyase contains a stable flavin radical that is readily photoreduced in the presence of added electron donors. Picosecond, nanosecond, and conventional flash photolysis technique have been employed to investigate the events leading to photoreduction from 40 ps to tens of milliseconds following flash excitation. Direct light absorption by the flavin radical produces the first excited doublet state which undergoes rapid (within 100 ps) intersystem crossing to yield the lowest excited quartet (n pi*) state. In contrast, light absorption by the folate chromophore produces a new intermediate state via interaction of the folate excited singlet state with the ground-state flavin radical, leading to an enhanced yield of the excited radical doublet state and hence quartet state. Subsequent reaction of the excited quartet state involves hydrogen atom abstraction from a tryptophan residue. Secondary electron transfer from added electron donors occurs to the oxidized tryptophan radical with rate constants ranging from 10(4) (dithiothreitol) to 4 x 10(6) M-1 s-1 (n-propyl gallate). The low value of the latter rate compared to reduction of the tryptophan radical in lysozyme suggests that the reactive tryptophan is highly buried in photolyase. A redox potential diagram has been constructed for the ground and excited states involved. It is concluded that the one-electron reduction potential of the excited quartet state of the flavin radical must be at least 1.23 V more positive than the ground state, in agreement with the value of delta E greater than 1.77 V calculated from spectroscopic data. PMID- 2200511 TI - Active site of Escherichia coli DNA photolyase: mutations at Trp277 alter the selectivity of the enzyme without affecting the quantum yield of photorepair. AB - Escherichia coli DNA photolyase repairs pyrimidine dimers by a photoinduced electron-transfer reaction. The enzyme binds to UV-damaged DNA independent of light (the dark reaction) and upon absorbing a 300-500-nm photon breaks the cyclobutane ring of the dimer (the light reaction) and thus restores the DNA. No structural information on the enzyme is available at present. However, comparison of the sequences of photolyases from five different organisms has identified highly conserved regions of homology. These regions are presumably involved in chromophore (flavin and folate) and substrate binding or catalysis. Trp277 (W277) in E. coli photolyase is conserved in all photolyases sequenced to date. We replaced this residue with Arg, Glu, Gln, His, and Phe by site-specific mutagenesis. Properties of the mutant proteins indicate that W277 is involved in binding to DNA but not in chromophore binding or catalysis. Of particular significance is the finding that compared to wild type W277R and W277E mutants have about 300- and 1000-fold lower affinity, respectively, for substrate but were indistinguishable from wild-type enzyme in their photochemical and photocatalytic properties. PMID- 2200512 TI - Reconstitution of Escherichia coli photolyase with flavins and flavin analogues. AB - Escherichia coli DNA photolyase contains two chromophore cofactors, 1,5 dihydroflavin adenine dinucleotide (FADH2) and (5,10 methenyltetrahydrofolyl)polyglutamate (5,10-MTHF). A procedure was developed for reversible resolution of apophotolyase and its chromophores. To investigate the structures important for the binding of FAD to apophotolyase and of photolyase to DNA, reconstitution experiments with FAD, FMN, riboflavin, 1-deazaFAD, 5 deazaFAD, and F420 were attempted. Only FAD and 5-deazaFAD showed high-affinity binding to apophotolyase. The apoenzyme had no affinity to DNA but did regain its specific binding to thymine dimer containing DNA upon binding stoichiometrically to FAD or 5-deazaFAD. Successful reduction of enzyme-bound FAD with dithionite resulted in complete recovery of photocatalytic activity. PMID- 2200513 TI - Substrate overlap and functional competition between human nucleotide excision repair and Escherichia coli photolyase and (a)BC excision nuclease. AB - Human cell free extract prepared by the method of Manley et al. (1980) carries out repair synthesis on UV-irradiated DNA. Removal of pyrimidine dimers by photoreactivation with DNA photolyase reduces repair synthesis by about 50%. With excess enzyme in the reaction mixture photolyase reduced the repair signal by the same amount even in the absence of photoreactivating light, presumably by binding to pyrimidine dimers and interfering with the binding of human damage recognition protein. Similarly, the UvrB subunit of Escherichia coli (A)BC excinuclease when loaded onto UV-irradiated or psoralen-adducted DNA inhibited repair synthesis by cell-free extract by 75-80%. The opposite was true also as HeLa cell free extract specifically inhibited the photorepair of a thymine dimer by DNA photolyase and its removal by (A)BC excinuclease. Cell-free extracts from xeroderma pigmentosum (XP) complementation groups A and C were equally effective in blocking the E. coli repair proteins, while extracts from complementation groups D and E were ineffective in blocking the E. coli enzyme. These results suggest that XP-D and XP-E cells are defective in the damage recognition subunit(s) of human excision nuclease. PMID- 2200514 TI - 1H NMR resonance assignments, secondary structure, and global fold of Apo bovine calbindin D9k. AB - The solution structure and dynamics of apo bovine calbindin D9k have been studied by a wide range of two-dimensional 1H nuclear magnetic resonance experiments. Due to the presence of conformational heterogeneity in the wild-type protein, the sequential resonance assignment was carried out on a Pro43----Gly mutant. By use of a combination of scalar correlation experiments acquired from H2O solution, 61 of the 76 1H spin systems could be assigned to particular amino acid types. The remaining resonances were assigned by a parallel series of experiments acquired from 2H2O solution. These spin system assignments provided a basis for complete sequential resonance assignments from interresidue backbone nuclear Overhauser effects (NOEs). Elements of secondary structure were identified from sequential and medium-range NOEs, backbone spin-spin coupling constants, and slowly exchanging amide protons. Four sections of helix are delineated, together with a short antiparallel beta-sheet interaction between the peptide loops involved in Ca2+ binding. The global fold is provided by combining these elements of secondary structure with a subset of the long-range, interhelix NOEs. Comparison with similar studies on the Ca2(+)-saturated protein indicates that at this crude level the structures are very similar. However, removal of the Ca2+ does dramatically affect the dynamics of the protein, as judged by amide proton exchange rates and aromatic ring rotation. This is particularly evident in the increased flexibility of the residues in the hydrophobic core. PMID- 2200515 TI - Rotational resonance determination of the structure of an enzyme-inhibitor complex: phosphorylation of an (aminoalkyl)phosphinate inhibitor of D-alanyl-D alanine ligase by ATP. AB - We have used a newly developed solid-state NMR method, rotational resonance, to establish the structure of an inhibited complex formed upon reaction of D-alanyl D-alanine ligase, ATP, and the aminoalkyl dipeptide analogue [1(S)-aminoethyl][2 carboxy-2(R)-methyl-1- ethyl]phosphinic acid (Ib). Analogue Ib was determined to be an ATP-dependent, slow-binding inhibitor of the D-Ala-D-Ala ligase from Salmonella typhimurium, with an enzyme-inhibitor half-life of 17 days at 37 degrees C. The inhibited complex shows a 31P NMR spectrum which is very different from that which would arise from a mixture of the free inhibitor and ATP. Four well-resolved lines were observed: two (at -8 and -14 ppm) are assignable as the phosphates of ADP, the third is assignable to an inhibitor resonance (at 53 ppm) that shifts by approximately 19 ppm on binding, and the fourth is assignable to a resonance (at -3 ppm) due to a polyphosphate or phosphate ester moiety. At rotational resonance the spectrum shows evidence for strong dipolar couplings between the phosphinate phosphorus and a phosphate ester species. The dipolar coupling between the phosphorus signals at 53 and -3 ppm was measured at rotational resonance by use of numerical simulations of both the line shape of the signal and the profile of magnetization transfer between the two sites. The measured coupling, 1.0 +/- 0.2 kHz, indicates that the two species are bridged in a P-O-P linkage, with a P-P through-space distance of 2.7 +/- 0.2 A. This proves that the mechanism of inactivation involves phosphorylation of the enzyme-bound inhibitor by ATP to form a phosphoryl-phosphinate adduct. PMID- 2200516 TI - Glutathione reductase: comparison of steady-state and rapid reaction primary kinetic isotope effects exhibited by the yeast, spinach, and Escherichia coli enzymes. AB - Kinetic parameters for NADPH and NADH have been determined at pH 8.1 for spinach, yeast, and E. coli glutathione reductases. NADPH exhibited low Km values for all enzymes (3-6 microM), while the Km values for NADH were 100 times higher (approximately 400 microM). Under our experimental conditions, the percentage of maximal velocities with NADH versus those measured with NADPH were 18.4, 3.7, and 0.13% for the spinach, yeast, and E. coli enzymes, respectively. Primary deuterium kinetic isotope effects were independent of GSSG concentration between Km and 15Km levels, supporting a ping-pong kinetic mechanism. For each of the three enzymes, NADPH yielded primary deuterium kinetic isotope effects on Vmax only, while NADH exhibited primary deuterium kinetic isotope effects on both V and V/K. The magnitude of DV/KNADH at pH 8.1 is 4.3 for the spinach enzyme, 2.7 for the yeast enzyme, and 1.6 for the E. coli glutathione reductase. The experimentally determined values of TV/KNADH of 7.4, 4.2, and 2.2 for the spinach, yeast, and E. coli glutathione reductases agree well with those calculated from the corresponding DV/KNADH using the Swain-Schaad expression. This suggests that the intrinsic primary kinetic isotope effect on NADH oxidation is fully expressed. In order to confirm this conclusion, single-turnover experiments have been performed. The measured primary deuterium kinetic isotope effects on the enzyme reduction half-reaction using NADH match those measured in the steady state for each of the three glutathione reductases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2200517 TI - On the nature of the structural change of the colicin E1 channel peptide necessary for its translocation-competent state. AB - Acidic pH conditions required in vitro for membrane binding and activity of the channel-forming colicin E1 resulted in an increased susceptibility to proteases of the 178-residue thermolytic channel peptide, an increased accessibility to acrylamide of a fluorescence probe linked to cysteine-505 of the peptide, and an increased partition into nonionic detergent. The structural change in the peptide sensed by the fluorescence probe caused by a transition from pH 6.0 to 3.5 occurred in less than 1 s. The presence of low concentrations of detergents (0.001% SDS or 0.44% octyl beta-D-glucoside) or urea (0.2 M) at pH 6 or 4 also increased the susceptibility of the channel peptide to proteases. The increase in protease susceptibility and acrylamide accessibility at low pH, as well as partition of the peptide into nonionic detergent, suggested that acidic pH or the detergents might cause peptide unfolding. However, the hydrodynamic radius of the channel peptide at pH 6, 21-23 A, was not changed at pH 3.5 or by detergents or urea under conditions that increased the susceptibility of the peptide to protease. The activity of the channel peptide at pH 6 measured with liposomes and planar bilayers, which was a factor of 10(3)-10(4) smaller than that at pH 4, was increased by 2-4 orders of magnitude by 0.001% SDS or 0.44% octyl beta-D glucoside, with an additional small increment of activity on planar bilayers caused by 0.01% SDS. A small increase in Stokes radius of the peptide in the presence of SDS could be detected that was approximately correlated with increased activity. PMID- 2200518 TI - Initiation of mRNA translation in prokaryotes. PMID- 2200519 TI - Kinetics of interaction of nucleotides with nucleotide-free H-ras p21. AB - A method is described for the convenient preparation of substantial quantities of nucleotide-free p21 or of 1:1 complexes with nucleotides other than GDP. The nucleotide-free protein has been used for kinetic studies of the binding of GDP and GTP, making use of the fluorescent analogues 3'-(methylanthraniloyl)-2'-deoxy GDP and -GTP. Stopped-flow studies have led to the formulation of a two-step binding mechanism for both GDP and GTP, involving initial rapid but weak binding of the nucleotide followed by a relatively slow (10-20 s-1 at 25 degrees C; 3-5 s 1 at 5 degrees C) quasi-irreversible isomerization reaction. By use of a nonequilibrium competition method, guanosine and GMP have been shown to interact weakly but significantly with p21 (dissociation constants of 153 and 29 microM, respectively). The presence of guanosine or GMP at the active site of p21 leads to a marked stabilization of p21 against spontaneous denaturation when compared with the nucleotide- and nucleoside-free protein. PMID- 2200520 TI - Formation of a stable L-ascorbic acid alpha-glucoside by mammalian alpha glucosidase-catalyzed transglucosylation. AB - Enzymatic transglucosylation from maltose to L-ascorbic acid (AA) with mammalian tissue homogenates was determined by a high-performance liquid chromatography method and compared with the reaction catalyzed by alpha-glucosidase from Aspergillus niger. The homogenates of small intestine and kidney had a high transglucosylase activity to form a new type of glucosylated AA, which was associated with alpha-glucosidase activity. The new compound was demonstrated to be an equimolar conjugate of AA and glucose by the spectral and quantitative analyses. In particular, it showed a high stability in a neutral solution and no reducing activity toward cytochrome c and a dye. These properties were very different from those of AA and L-ascorbic acid alpha-glucoside formed with alpha glucosidase from A. niger, but they were consistent with those of L-ascorbic acid 2-O-phosphate and L-ascorbic acid 2-O-sulfate. Moreover, it exhibited a reducing power associated with AA after mild acid hydrolysis or treatment with rat intestinal alpha-glucosidase. These results indicate that it should be assigned the 2-O-alpha-glucoside structure. Consequently, it is concluded that mammalian alpha-glucosidase is able to form a very stable and nonreducing form of glucosylated AA through a specific transglucosylation reaction distinct from that of microbial alpha-glucosidase. PMID- 2200521 TI - Structural features of the HMG chromosomal proteins and their genes. PMID- 2200523 TI - Protein phosphorylation during the asexual life cycle of the human malarial parasite Plasmodium falciparum. AB - Recent evidence has suggested that extensive changes in the phosphorylation profile of red cell membrane proteins are associated with the invasion and development of the malarial parasite. In order to further define the role of parasite protein phosphorylation in these events we have looked at this phosphorylation using: (1) continuous metabolic labelling with [32P]orthophosphate, (2) pulse-labelling with [32P]orthophosphate and [35S]methionine, (3) autophosphorylation of infected cells using [gamma-32P]ATP, (4) invasion of prelabelled red cells. Many parasite proteins were labelled, some differentially according to the phosphorylation protocol employed, and we were able to partially characterise several of the major parasite phosphoproteins in terms of their association with host cell membrane and the stage specificity of phosphorylation. PMID- 2200522 TI - Comparison of secretory expression in Escherichia coli and Streptomyces of Streptomyces subtilisin inhibitor (SSI) gene. AB - To elucidate differences in the mechanism of gene expression between Streptomyces and Escherichia coli, the regulatory region for expression of the gene for a proteinaceous proteinase inhibitor, Streptomyces subtilisin inhibitor (SSI), was altered to express efficiently in E. coli. This was carried out by inserting a pre-SSI-encoding region downstream of the tac promoter and ribosome-binding site in a multi-copy plasmid. When the resultant plasmid pMKSI161-9 was introduced into E. coli JM105, SSI protein was found to be expressed and secreted into the periplasmic space by Western blot analysis. When introduced into 'leaky' E. coli strains, this protein was detected in the medium as well as in the periplasmic space in bacteria. NH2-terminal sequencing analysis of the SSI purified from E. coli JM105 indicated two processing sites, Ala(-4)/Ala(-3)-Pro(-2)-Gly and Ala( 4)-Ala-3/Pro(-2)-Gly-1, of pre-SII. These sites were different from those in Streptomyces albogriseolus S-3253 and Streptomyces lividans 66. The inhibitor activity of the processed protein toward subtilisin BPN' was almost the same as that of authentic SSI. PMID- 2200524 TI - Radioisotopic measurement of femtomolar amounts of NAD(P)H in the assay of enzymatic activity at a single cell level. AB - A radioisotopic method for the assay of reduced or oxidized pyridine nucleotides, based on the interconversion of 2-[U-14C]ketoglutarate or 2-keto[3,4-3H]glutarate and labelled L-glutamate in the reaction catalyzed by glutamate dehydrogenase, was applied to the measurement of lactate dehydrogenase activity in rat pancreatic islet homogenates. Using the tritiated tracer, the limit of sensitivity of the procedure for NAD(P)H assay was close to 1.0 fmol/sample, and lactate dehydrogenase activity could be measured in as little as 0.0005 islet/sample i.e., at a single cell level. This radioisotopic procedure, which can be used for the assay of various metabolites and enzymic activities, thus provides a tool for investigating the heterogeneity in metabolic behaviour of individual cells. PMID- 2200525 TI - The ligand binding characteristics of a kinase-defective A/K1018 human insulin receptor expressed in Rat 1 fibroblasts. AB - Expression of the cDNA encoding a human insulin receptor with replacement of alanine for lysine at residue 1018 in the ATP binding domain of the beta subunit results in a receptor that is not only kinase-defective, but also biologically inactive. Interestingly, this mutated receptor shows a decreased insulin binding affinity when expressed at high level. We, therefore, studied the binding property of this mutant receptor expressed in Rat 1 fibroblasts. The association rate (Ka) of insulin to the mutant receptor was comparable to normal, but the dissociation rate (Kd) was twice as fast. Furthermore, the Kd of the mutant receptor was also more sensitive to changes in pH, accelerating more rapidly with pH changes than did the Kd of normal receptors. Despite this difference, the mutant receptor still exhibited negative cooperativity. These results indicate that the loss of tyrosine kinase activity of the beta subunit of the insulin receptor leads to alteration of the ligand binding affinity of the alpha subunit. PMID- 2200527 TI - Transducin activation and deactivation in rod systems of different structural integrity. Attempts at a focussed view through scattered light. PMID- 2200526 TI - The mechanism of action of the nitrosourea anti-tumor drugs on thioredoxin reductase, glutathione reductase and ribonucleotide reductase. AB - The nitrosoureas BCNU, CCNU, ACNU, and Fotemustine covalently deactivate thioredoxin reductase, glutathione reductase and ribonucleotide reductase by alkylating their thiolate active sites. Since thioredoxin reductase and glutathione reductase function as alternative electron donors in the biosynthesis of deoxyribonucleotides, catalyzed by ribonucleotide reductase, the inhibition of these electron transfer systems by the nitrosoureas could determine the cytostatic property of this homologous series of drugs. A detailed study of the kinetics and mechanism for the inhibition of purified thioredoxin reductases from human metastatic melanotic and amelanotic melanomas by the nitrosoureas showed significantly different inhibitor constants. This difference is due to the regulation of these proteins by calcium. Calcium protects thioredoxin reductase from deactivation by the nitrosoureas. In addition, it has been shown that reduced thioredoxin displaces the nitrosourea-inhibitor complex from the active site of thioredoxin reductase to fully reactivate enzyme purified from human metastatic amelanotic melanoma. It has been possible to label the active sites of thioredoxin reductase and glutathione reductase by using chloro[14C]ethyl Fotemustine, resulting in the alkylation of the thiolate active sites to produce chloro[14C]ethyl ether-enzyme inhibitor complexes. These complexes can be reactivated via reduced thioredoxin and reduced glutathione, respectively, by a beta-elimination reaction yielding [14C]ethylene and chloride ions as reaction products. PMID- 2200529 TI - Different effects of two proteinase inhibitors on insulin-induced cellular responses in rat adipocytes. AB - Among various proteinase inhibitors, N-acetyl-L-tyrosine ethyl ester (ATEE), a chymotrypsin substrate analog, and N alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK), a trypsin inhibitor, showed significant inhibitory effects on insulin stimulated glucose transport in rat adipocytes. ATEE did not affect insulin binding, but inhibited insulin internalization. In intact adipocytes, ATEE inhibited tyrosine phosphorylation of the beta-subunit of the insulin receptor, a 170 kDa protein and a 60 kDa protein at almost the same concentration (ID50 = 0.24 +/- 0.05 mM, n = 4, mean +/- S.E.), but in a plasma membrane fraction, ATEE did not appreciably inhibit the tyrosine phosphorylation of the beta-subunit of the insulin receptor, TLCK did not inhibit insulin binding. At 0.25 mM, TLCK did not inhibit insulin internalization, but inhibited 70% of the insulin-stimulated glucose transport (ID50 = 0.19 +/- 0.02 mM, n = 7). TLCK inhibited insulin internalization at more than 0.25 mM. TLCK did not inhibit the tyrosine phosphorylation of the beta-subunit of the insulin receptor in intact cells or in the plasma membrane fraction. In intact cells, TLCK inhibited the phosphorylation of the 60 kDa protein and simultaneously it stimulated the phosphorylation of the 170 kDa protein more than 3-fold. These results indicate that there are at least two sites in the insulin-induced signal transduction pathway where proteinase inhibitors act to suppress the insulin signal transduction. A major ATEE site is very close to phosphorylation of the beta-subunit of the insulin receptor. On the other hand, TLCK inhibits a step(s) in the signal transduction pathway after the insulin receptor but before the glucose transporter. PMID- 2200528 TI - Insulin, epidermal growth factor and fibroblast growth factor elicit distinct patterns of protein tyrosine phosphorylation in BC3H1 cells. AB - The polypeptides which are phosphorylated at tyrosine residues in the murine muscle-like cell line, BC3H1, in response to insulin, epidermal growth factor (EGF) and fibroblast growth factor (FGF) were detected by immunoblotting with antiphosphotyrosine antibodies. Each ligand elicited the tyrosine phosphorylation of a characteristic, largely nonoverlapping set of polypeptide substrates, as classified by subunit Mr, pI, behavior on subcellular fractionation and adsorption to lectin (what germ agglutinin-Sepharose) columns. The dose-response curves for all stimulated tyrosine phosphorylations elicited by a single ligand were superimposable. By contrast, the temporal pattern of the responses elicited by each ligand differed in regard to speed of onset and persistence of the stimulation. Phosphorylation in response to insulin was maximal in a virtually instantaneous fashion and was fully maintained for at least 30 min. The response to EGF increased steadily over the initial 15-60 s to peak values, and fell progressively thereafter. FGF-stimulated phosphorylation was not detectable until 4 min after FGF addition, abruptly rose to maximal within the next 30 s, and declined subsequently. Exposure of BC3H1 cells to active phorbol esters prior to hormone addition altered the response to hormones in a differential fashion. FGF responses were abolished, EGF responses were partially inhibited, whereas the response to insulin was unaffected. Thus, acting on a single cell, insulin, EGF and FGF each mediate the tyrosine phosphorylation of a characteristic, largely nonoverlapping array of polypeptide substrates, indicating that each of these receptor tyrosine kinases exhibits a fundamentally distinct substrate specificity. Differences in the kinetic and regulatory properties of the response to each ligand are also apparent, and reflect the differing regulatory properties of each receptor tyrosine kinase acting in situ. PMID- 2200530 TI - Protein kinase C activation patterns are determined by methodological variations. Studies of insulin action in BC3H-1 myocytes and rat adipose tissue. AB - In BC3H-1 myocytes, insulin has been reported to (a) increase diacyglycerol (DAG) production and provoke increases in protein kinase C enzyme activity of crude or DEAE-Sephacel-purified cytosol and membrane fractions in BC3H-1 myocytes (Cooper et al. (1987) J. Biol. Chem. 262, 3633-3739), but (b) decrease cytosolic, and transiently increase membrane, immunoreactive protein kinase C (Acevedo-Duncan et al. (1989) FEBS Lett. 244, 174-176). Presently, we used a Mono-Q column to purify protein kinase C and found that, similar to immunoblot findings, enzyme activity decreased in the cytosol, and increased in the membrane during insulin treatment. Similar differences in protein kinase C activation patterns were observed in rat adipose tissue: insulin stimulated cytosolic protein kinase C enzyme activity as measured after DEAE-Sephacel chromatography, but decreased cytosolic enzyme activity when measured after Mono-Q chromatography or by immunoblotting. We presently evaluated the possibility that insulin-induced increases in endogenous DAG may influence protein kinase C during assay in vitro. Crude cytosol from BC3H 1 myocytes contained 25-35% of total and [3H]glycerol-labelled DAG and insulin increased this DAG. Considerable amounts of [3H]glycerol-labelled DAG were present in insulin-stimulated protein kinase C-containing column fractions following DEAE-Sephacel chromatography of cytosol fractions, whereas lesser amounts were recovered after Mono-Q column chromatography. This difference in recovery of DAG and activation of the enzyme by this endogenous DAG may explain why we were able to discern insulin-induced (presumably translocation 'provoked') decreases in cytosolic protein kinase C in the present Mono-Q column preparations of both BC3H-1 myocytes and rat adipose tissue. PMID- 2200531 TI - [The constitutive and induced synthesis of exodepolymerases by micromycetes]. AB - The enzymatic activity of micromycetes of Aspergillus and Penicillium genera cultivated on substrate containing substances media and without them has been studied. The promising producers of pectin-transeliminases, proteases and model organisms for study of constitutive synthesis of exoenzymes have been selected. PMID- 2200532 TI - [The temperature of the internal environment as one of the mechanisms regulating the internal organs. The regulation of the rate of cardiac contractions by the temperature of the venous inflow]. AB - A review of literature devoted to the inner medium temperature as one of the regulation mechanisms in functioning of internal organs is given. The temperature of venous inflow has been shown to be of great importance in regulation of the heart hemodynamic productivity. PMID- 2200533 TI - In vivo biocompatibility of collagen-poly(hydroxyethyl methacrylate) hydrogels. AB - Collagen-p(HEMA) hydrogels were subcutaneously implanted in rats for up to 6 month and the immediate short- and long-term tissue response to these implants was studied. Histopathological data indicated that the tissue reaction at the implant site progressed from an initial acute inflammatory response characterized by the presence of eosinophils and polymorphs to a chronic response marked by few macrophages, foreign body giant cells and fibroblasts. After one month a very thin fibrous capsule (approximately 11 microns thick) was observed around the implant. Even 6 month post-implantation, the capsule thickness was maintained at about 11-12 microns. No necrosis, calcification, tumorigenesis or infection was observed at the implant site up to 6 month. Fibrous capsule analysis showed that the collagen content and the capsule thickness were well within the threshold limits. The collagen-p(HEMA) hydrogels were found to be well-tolerated, non-toxic and highly biocompatible. PMID- 2200534 TI - Study of mechanisms of electric field-induced DNA transfection. I. DNA entry by surface binding and diffusion through membrane pores. AB - A study of mechanisms of electrotransfection using Escherichia coli (JM 105) and the plasmid DNA pBR322 as model system is reported. pBR322 DNA carries an ampicillin resistance gene: E. coli transformants are conveniently assayed by counting colonies in a selection medium containing 50 micrograms/ml ampicillin and 25 micrograms/ml streptomycin. Samples not exposed to the electric field showed no transfection. In the absence of added cations, the plasmid DNA remains in solution and the efficiency of the transfection was 2 x 10(6)/micrograms DNA for cells treated with a 8-kV/cm, 1-ms electric pulse (square wave). DNA binding to the cell membrane greatly enhanced the efficiency of the transfection and this binding was increased by milimolar concentrations of CaCl2, MgCl2, or NaCl (CaCl2 greater than MgCl2 greater than NaCl). For example, in the presence of 2.5 mM CaCl2, 55% of the DNA added bound to E. coli and the transfection efficiency was elevated by two orders of magnitude (2 x 10(8)/micrograms DNA). These ions did not cause cell aggregation. With a low ratio of DNA to cells (less than 1 copy/cell), transfection efficiency correlated with the amount of DNA bound to the cell surface irrespective of salts. When the DNA binding ratio approached zero, the transfection efficiency was reduced by two to three orders, indicating that DNA entry by diffusion through the bulk solution was less than 1%. Square pulses of up to 12 kV/cm and 1 ms were used in the electrotransfection experiments. When cell concentration was 1 x 1010 cell/ml and DNA was added before the pulse, a transfection efficiency of up to 5 x 108/ microg DNA was obtained under optimum conditions (a single pulse of 8 kV/cm, 1 ms, in the presence of 5 mM CaCl2). When DNA was added to E. coli after the electric pulse, the efficiency of the transfection was dramatically reduced owing to the resealing of pores. Transfection was reduced to zero when DNA was added 2 h after the electroporation. However, transfection as high as 5 x 104/microg DNA was still recorded when DNA was added 10 min after the electric field was turned off. Because DNA entry took place in the absence of an electric field it could not be driven by the electrophoretic forces. DNA entry was facilitated by surface binding followed by lateral diffusion of the bound DNA into the cells through the field-induced membrane pores. PMID- 2200535 TI - Inflammation and cancer: role of phagocyte-generated oxidants in carcinogenesis. AB - We have reviewed some of the data that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. While it is clear that these substances induce phenotypic changes characteristic of those produced by known carcinogens, the precise mechanisms by which these effects are produced require much further study. In vitro, it would appear that phagocyte-generated oxidants could be complete carcinogens, ie, could cause both tumor initiation and promotion. In vivo, however, these substances appear usually to function as tumor promoters or cocarcinogens perhaps because of high levels of endogenous antioxidant defenses. This suggests that there may be even more reason to be optimistic about the potential for positive results in cancer chemoprevention trials in humans, and provides further rationale for the continuing interest in the use of antioxidants and anti-inflammatory drugs in current and future trials. For example, the Chemoprevention Branch of the National Cancer Institute is currently sponsoring seven extramural human efficacy intervention trials testing whether the antioxidant beta carotene can prevent cancer. PMID- 2200536 TI - High-dose melphalan and granulocyte-macrophage colony-stimulating factor for refractory multiple myeloma. AB - High-dose melphalan has induced remissions in about 40% of patients with refractory myeloma, but the mortality has been high, at about 20%, due to complications of prolonged granulocytopenia. In an attempt to stimulate earlier granulocyte recovery, recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered subcutaneously to 23 patients with refractory myeloma who had been treated with melphalan at a high dose of 100 mg/m2. Thirty nine percent of patients achieved marked tumor cytoreduction by at least 75%, 2 died within 2 months from infectious complications during severe neutropenia; and median durations of relapse-free and overall survival were 7 and 10+ months, respectively. The nine patients presenting with both advanced age over 50 years and a long history of prior therapy of over 1 year required significantly longer median times of 31 days for granulocytes and of 63 days for platelets to reach safe levels of at least 500/microL and 50,000/microL, respectively, than the 14 remaining patients who had none or only one of these adverse features (21 and 26 days, respectively). In a historic control of 43 patients treated previously with high-dose melphalan but without GM-CSF, hematologic recovery to the aforementioned levels of granulocytes and platelets proceeded over almost 5 weeks, regardless of age and prior treatment exposure. Thus GM-CSF seems to hasten marrow recovery, especially in patients with adequate normal marrow stem cell reserve as defined by younger age or less prior therapy. While not shortening the duration of neutropenia, GM-CSF dose increments (from 0.25 to 0.5 to 0.75 mg/m2) increased the incidence of severe toxicity from 0% to almost 40%, especially among older patients. These results support the usefulness of low-dose GM-CSF (0.25 mg/m2) in stimulating marrow recovery in selected patients with adequate marrow reserve treated with high-dose melphalan for refractory multiple myeloma. PMID- 2200537 TI - The action of bryostatin on normal human hematopoietic progenitors is mediated by accessory cell release of growth factors. AB - Since enrichment of human bone-marrow hematopoietic progenitors is becoming more feasible and since purified growth factors are now available, we sought to study the action of growth factors on CD34-positive enriched cultures of human bone marrow cells. We tested the effect of recombinant human (rh) granulocyte macrophage colony-stimulating factor (GM-CSF), rh interleukin-3 (IL-3), or a unique biologic response modifier, bryostatin 1, on the growth of purified CD34 cells obtained by limiting dilution in single-cell cultures. We have shown previously that bryostatin 1 stimulates both myeloid and erythroid progenitors of human origin in vitro. In this study both IL-3 and GM-CSF supported colony formation from 500, 100, or single-cell cultures at equivalent plating efficiences, suggesting a direct action of these factors on hematopoietic cell growth. Conversely, bryostatin 1 did not support the growth of CD34 cells in single-cell cultures, and the cloning efficiency increased with increasing the number of cells in the culture. To test whether the indirect action of bryostatin 1 might be mediated through the production of growth factors by accessory cells, studies were performed using antibodies directed against human IL-3 and GM-CSF in culture with bryostatin 1 and normal human bone-marrow cells. Results are consistent with the hypothesis that bryostatin 1 could have a stimulatory effect on the accessory cell populations to produce either IL-3 or GM-CSF. Further support for this notion was obtained by demonstrating that T cells, which are cells known to be able to produce IL-3 and GM-CSF, are stimulated by bryostatin 1 to express messenger RNA (mRNA) for specific growth factors, including GM-CSF. These results provide further support that bryostatin 1 may be a useful clinical agent to stimulate hematopoiesis in vivo. PMID- 2200538 TI - Molecular genetics of gastrointestinal non-Hodgkin's lymphomas: unusual prevalence and pattern of c-myc rearrangements in aggressive lymphomas. AB - Thirty-two extranodal lymphomas of the gastrointestinal (GI) tract underwent molecular genetic analysis by Southern blotting using probes for the immunoglobulin genes and the bcl-1, bcl-2, and c-myc loci, commonly involved in lymphomagenesis. No bcl-1 rearrangements were found. There was only one large cell lymphoma with a bcl-2 rearrangement. A rearrangement of the c-myc gene was found in six of eight Burkittlike lymphomas of the intestine. In five of these six cases, a chromosomal translocation t(8;14) with an unusual breakpoint was demonstrated by comigration of the rearranged c-myc and a rearranged JH sequence. This pattern of rearrangement has not been previously associated with a specific group of non-Hodgkin's lymphomas. In contrast to all six low-grade lymphomas, c myc rearrangements were found in 6 of 12 large-cell or high-grade mucosa associated lymphomas of the stomach. No comigration of c-myc and immunoglobulin heavy-chain gene sequences were found. We conclude that primary GI lymphomas have different molecular genetic characteristics compared with node-based follicle center-cell lymphoma and as a group are not related to these lymphomas. In addition, the prevalence and patterns of c-myc rearrangements in the gastric large-cell lymphomas and ileocecal Burkittlike lymphomas are noteworthy and suggest a different and distinct pathogenesis for these tumors. PMID- 2200539 TI - N-ras mutations in adult de novo acute myelogenous leukemia: prevalence and clinical significance. AB - Point mutations of the N-ras proto-oncogenes have been previously detected in 20% to 60% of samples of acute myelogenous leukemia (AML), but the clinical significance of these mutations is presently unclear. We directly sequenced polymerase chain reaction (PCR) amplified N-ras fragments to determine the frequency of N-ras point mutations in 55 adult patients with de novo AML. Mutations were present in 8 of 55 (15%) patients. These mutations were usually in codon 12, 13, or 61, but one patient had mutations in both codons 13 and 61, and another had an unusual point mutation in N-ras codon 60. A comparison of patients with and without N-ras mutations showed no statistically significant differences in pretreatment clinical variables, response to induction therapy, or survival, except for a possibly higher percentage of FAB M4 subtypes in patients with the N ras mutation. These data together with previous reports suggest that the presence of N-ras point mutations do not clearly define a unique clinical or biologic subset of AML patients. PMID- 2200540 TI - The ontogeny of a 57-Kd cationic antimicrobial protein of human polymorphonuclear leukocytes: localization to a novel granule population. AB - The ontogeny of a 57-Kd cationic antimicrobial protein (CAP57) that has substantial similarities to bactericidal permeability increasing protein (BPI) has been determined immunocytochemically. CAP57 was detected in the granules of mature peripheral blood neutrophils. However, it was absent from other cells of the peripheral blood: eosinophils, red blood cells (RBCs), and mononuclear cells. In human bone marrow, CAP57 was confined to the neutrophilic series. The earliest stage of development of the myeloid cells at which CAP57 was demonstrated was the promyelocyte. Double immunofluorescent labeling showed that CAP57 was detected in cells positive for myeloperoxidase. The absence of lactoferrin in certain cells (promyelocytes) containing CAP57 indicated that CAP57 was synthesized and packaged in a population of granules prior to the development of granules that contain lactoferrin. CAP57 could not be demonstrated in HL60 cells either by enzyme-linked immunosorbent assay (ELISA) or by immunocytochemistry. However, the presence of another granule-associated cationic antimicrobial protein of molecular weight 37 Kd (CAP37) was readily detected in undifferentiated HL60 cells. Amino acid sequence analysis showed that CAP57 and BPI were identical. Further indication of the identity between CAP57 and BPI was that monoclonal anti CAP57 antibodies cross reacted with BPI. Sucrose density-gradient centrifugations showed CAP57 was confined to a granule population that exhibited a buoyant density intermediate of the previously described light and heavy azurophil granules. Further resolution of the individual azurophil granule populations by Percoll density-gradient centrifugation revealed that CAP57 was most concentrated in the density range of 1.093 to 1.100 g/cc. These results strongly suggest the unique finding that CAP57 may be associated with a heretofore unreported granule type. PMID- 2200541 TI - Detection of genotoxicants in a polluted watercourse by means of a yeast system. PMID- 2200542 TI - Low-level interferences in peroxyoxalate chemiluminescence. AB - The role of interferences at concentrations lower than 10(-3) M in peroxyoxalate chemiluminescence is examined based on experimental results available in the literature. Implications for fluorophore and for hydrogen peroxide determinations are discussed. An interpretation in terms of the reaction mechanism is proposed. PMID- 2200543 TI - Insulin injection technique. PMID- 2200544 TI - ABC of major trauma. Trauma of the spine and spinal cord--I. PMID- 2200545 TI - Creutzfeldt-Jakob disease. PMID- 2200546 TI - [Academic eulogy of Professor Paul Van Gehuchten, titular member and former president]. PMID- 2200547 TI - Diagnosis and management of mesenteric infarction. PMID- 2200548 TI - Management of severe acute cholangitis. PMID- 2200549 TI - Interaction of penetrating missiles with tissues: some common misapprehensions and implications for wound management. AB - It is apparent from review of published papers and books that misunderstanding and confusion exists in the minds of many authors describing the interaction of penetrating missiles with tissues. These misapprehensions may influence the management of wounds by suggesting didactic approaches based upon a preconceived notion of the nature and severity of the wound for different types of projectiles. This review considers the biophysics of penetrating missile wounds, highlights some of the more common misconceptions and seeks to reconcile the conflicting and confusing management doctrines that are promulgated in the literature-differences that arise not only from two scenarios, peace and war, but also from misapprehensions of the wounding process. Wounds of war and of peacetime differ both in the nature of the wound and in the propensity for wound infection. Additionally, the limitations imposed by war dictate the type of management that may be practised and result in procedures that would be considered inappropriate by some in civilian clinical practice. Many of the procedures described in civilian peacetime settings, such as reliance on antibiotics alone for the control of infection in penetrating wounds, or minimal excision and debridement, can yield good results but would herald disaster if transposed to a war setting. PMID- 2200550 TI - Comparison of Coloscreen Self-Test and Haemoccult faecal occult blood tests in the detection of colorectal cancer in symptomatic patients. AB - The usefulness of faecal occult blood tests is limited by their acceptability to patients. Standard tests require the collection of a stool sample which may inhibit compliance. Self-read tests which avoid this step have therefore been devised. Coloscreen Self-Test (CST) and Haemoccult, which may be regarded as the standard slide test, were offered to 450 consecutive patients attending surgical outpatient clinics with symptoms suggestive of lower gastrointestinal disease. Both tests were successfully completed by 383 patients. Although 262 (68 per cent) patients indicated that they preferred CST this was not reflected in the overall compliance to the two tests (CST 86 per cent, Haemoccult 90 per cent). CST gave a positive result in only eight out of 24 patients with a colorectal cancer (sensitivity = 33 per cent) compared with 13 out of 24 for Haemoccult (sensitivity = 54 per cent). CST had no advantage from increased compliance to outweigh its lower sensitivity. PMID- 2200551 TI - Prospective study of the value of ultrasound measurements in the diagnosis of acute rejection following renal transplantation. AB - In this prospective study we have used ultrasonographic measurements of the cross sectional area of transplanted kidneys, as an objective assessment of graft size, for diagnosis of acute rejection episodes. Sixty episodes of acute graft dysfunction (serum creatinine rise of greater than or equal to 30 mumol/l) were studied in 40 patients. Tru-Cut biopsy under ultrasound control was performed in all cases and 36 episodes of acute cellular rejection were identified. An increase in graft cross-sectional area of greater than or equal to 10 per cent was defined as a positive scan, indicative of an acute rejection episode. Using these criteria, ultrasound correctly diagnosed rejection in 29 out of 36 cases (sensitivity 81 per cent) and there were four false positive results (specificity 83 per cent). The investigation had a predictive value of 88 per cent when positive and 74 per cent when negative. PMID- 2200552 TI - Endoluminal ultrasound for early detection of local recurrence of rectal cancer. PMID- 2200553 TI - Minimally invasive surgery. PMID- 2200554 TI - Clinical relevance of sphincter of Oddi dysfunction. PMID- 2200555 TI - Tamoxifen therapy in unresectable adenocarcinoma of the pancreas and the papilla of Vater. AB - Between 1984 and 1987, 176 Norwegian patients with histologically verified unresectable pancreatic adenocarcinoma were randomized to double-blind treatment with oral tamoxifen (30 mg daily; 48 men and 44 women) or placebo (47 men and 37 women). Analysis of oestrogen receptor activity in the carcinomas was not performed. There were no statistically significant differences between the two groups according to age, Karnofsky performance index, tumour node metastasis (TNM) stage, operative treatment or other patient characteristics. The tamoxifen or placebo treatment continued to death or to 10 months after accrual into the trial was stopped. In the tamoxifen group, the mean and median survivals were 205 and 115 days, respectively. These values did not differ statistically from the 192 and 122 days, respectively, observed in the placebo group. Additional retrospective analyses of sex and stage revealed no beneficial effect of tamoxifen upon survival. For women in stage III (any T N1 M0), mean and median survivals were 255 and 191 days, respectively, compared with values of 84 and 45 days, respectively, in the placebo group (P = 0.011). After 2.5 years, three (7 per cent) women in the tamoxifen group were still alive compared with no survivors in the placebo group. No male patients survived beyond 2.5 years. This therapeutic result in a small subgroup of women is probably incidental and not an effect of tamoxifen. PMID- 2200556 TI - Gallstone ileus. AB - Thirty-seven patients (33 women and four men, median age 78 years) were operated on for gallstone ileus over a 12-year period with a median follow-up of 6.2 years. Twenty-three patients (62 per cent) had serious concomitant diseases. Plain abdominal radiographs performed at admission were diagnostic in only 17 patients (46 per cent) and other procedures such as ultrasonography, gastrointestinal contrast studies and computed tomographic scan were required in ten patients (27 per cent). The diagnosis was made before operation in 27 patients (73 per cent) but in only 17 (46 per cent) at admission. Obstructing stones were located in the terminal ileum in 27 patients (73 per cent), in the proximal ileum or jejunum in five (14 per cent), in the duodenum in two (5 per cent), and in the colon in three (8 per cent). In six instances (16 per cent), more than one stone was involved. Cholecystduodenal fistula was the most frequent fistula type (n = 25, 68 per cent), followed by cholecystcolonic (n = 2, 5 per cent) and cholecystduodenocolonic (n = 2, 5 per cent) types. The site of the fistula was not established in the other eight instances. A one-stage procedure consisting of the removal of the impacted stone, fistula repair and cholecystectomy was performed in eight patients, two of whom died. A second group of six patients underwent a two-stage procedure consisting of enterolithotomy followed by elective biliary surgery, with no mortality. Removal of impacted stones was the only surgical treatment in the remaining 23 patients, with five deaths. Operative mortality and morbidity rates associated with the initial procedure did not differ significantly among the three therapeutic groups, which were comparable in terms of patient age, associated concomitant diseases and APACHE II score. However, later biliary complications were prominent in patients treated only by enterolithotomy. These results support the view that a one-stage procedure is, when feasible, a valid option and may be the procedure of choice. When local or surgical conditions argue against a one-stage procedure, biliary surgery at a second stage should be considered, if residual stones are present. In poor risk patients, non-operative methods should be considered. PMID- 2200557 TI - Choice of incision and pain following gallbladder surgery. AB - A prospective randomized trial compared pain in the first 24 h after gallbladder surgery via an upper midline or a transverse incision. Pain was measured by the patients' self-administered consumption of pethidine, degree of postoperative respiratory impairment and a visual analogue pain scale. The upper midline incision group self-administered significantly more pethidine than the transverse incision group (P less than 0.001), but there was no difference between the groups in respiratory function or visual analogue pain scale results 24 h after operation. Length of hospital stay was not different. An upper midline incision is more painful than a transverse incision in the first 24 h following gallbladder surgery. PMID- 2200558 TI - Stapled Billroth I gastrectomy. PMID- 2200560 TI - Role of thallium-201/technetium-99m subtraction scanning in persistent or recurrent hypercalcaemia following parathyroidectomy. PMID- 2200561 TI - Evolution of catgut ligatures: the endeavours and success of Joseph Lister and William Macewen. PMID- 2200559 TI - Prospective randomized controlled trial of hepatic arterial embolization or infusion chemotherapy with 5-fluorouracil and degradable starch microspheres for colorectal liver metastases. AB - Survival benefit from hepatic artery embolization (HAE) or hepatic arterial infusion chemotherapy (HAI) in patients with unresectable colorectal liver metastases has not previously been assessed in a randomized controlled trial. Sixty-one patients were randomized, 20 to receive no treatment, 22 to receive HAE, and 19 to receive HAI with 5-fluorouracil and degradable starch microspheres. Both treatments were acceptable to the patients in terms of low treatment morbidity rate. Median survival from diagnosis of metastases was 9.6 months for controls, 8.7 months for the HAE group and 13.0 months in the HAI group. There was no apparent survival benefit for the HAE group. The increased survival in the HAI group was observed in all the subgroups analysed but failed to reach statistical significance. The greatest observed benefit was achieved in the subgroup with less than 50 per cent hepatic replacement with tumour at presentation (median survival from diagnosis 10.0 months for controls, 10.2 months for HAE and 23.6 months for HAI); 36 per cent of patients developed extrahepatic disease recurrence. No significant benefit has been shown from either HAE or HAI, but a more carefully selected group of patients with only low volume hepatic disease may benefit from HAI therapy. PMID- 2200562 TI - [Metabolic effects of indomethacin in irradiated rats]. AB - The effect of indomethacin on serum glucose, insulin, thyroid hormones and corticosterone and on liver glycogen in 9 Gy whole body gamma irradiated rats was studied. In the first experimental setting indomethacin was administered subcutaneously in the dose of 4 mg/kg body weight 24 hours before irradiation and sham irradiation, and the analyses were done 48 hours after irradiation. In the second setting indomethacin was administered by the same route immediately, 24, 48, and 72 hours after exposure and sham exposure, the analyses were done 120 hours after irradiation. Control groups were treated with phosphate buffer. Indomethacin inhibited partially the radiation-induced increase in serum glucose and corticosterone in both settings and the increase in liver glycogen in the first one. Indomethacin administration had no effect on serum insulin levels, but it decreased serum thyroxine concentration in irradiated and non-irradiated rats in the second setting. The administration of indomethacin in irradiated animals is accompanied by various metabolic alterations. PMID- 2200563 TI - Bone marrow transplantation: overview and nursing implications. PMID- 2200564 TI - [Prosthetic possibilities with the Denar "Steri-Oss" implant]. AB - Implantology, very frequently presented under only the surgical angle, must in fact be approached from a biological and functional point of view. The analysis of the future prosthetic situation will allow an overall treatment scheme to be established, in which periodontics, surgery, prosthodontics and occlusal equilibration will follow each other in order to achieve the functional rehabilitation. In the first part of this article, the various steps which make up the treatment scheme are briefly and quickly described. It is imperative to approach them according to this chronological order when there is any treatment involving implants. While implantology involved only one surgical session a few years ago, it now involves two: the first, consisting of placing the implant in the living tissues, and the second, at some months interval from the first, allowing the endo-osseous portion to be attached to the future prosthesis. These two surgical acts are inter-dependent. Given the wide array of systems proposed and the quantity of "Implant-Prosthesis" connections produced in each system, the practitioner does not always know which kind of connection to choose or how to use it. The second part of the article is devoted to the study of the various connection possibilities between the Steri-oss implants and the prosthesis. The methods for lining up the cores in relation to the others are studied in detail, as are the different possibilities for stabilising removable prosthesis. Some of the methods described can be used with other implant systems. PMID- 2200565 TI - [Operatory field in bonded dentures: proposals for a rationale]. AB - Success in acid-etched dentistry essentially depends on the quality of the adhesion. The bonding session must be carried out with the upmost rigour. The operative field will permit good protection against humidity (saliva, bleeding, gingival fluid, breathing), as well as good instrumental and visual access for finishing. Three different methods are available: retraction (retraction cords), isolation (rubber-dam, "contour strip"), and retraction + combined isolation (thick rubber-dam + suture; mini rubber-dam + suture. The indications depend on the localization in the mouth and the kind of restoration. It is thus necessary to classify the methods so that the selection of the operative field will be simple to work in, quick and systematic. The impossibility of isolating the surfaces to be bonded and to have an access to the margins must be an absolute counter-indication of this technique. PMID- 2200566 TI - [Multiple agenesis and prosthetic restoration]. AB - Cases of multiple agenesia present some difficulties in the treatment planing. Three situations may be encountered: limited agenesia, restored by a fixed, bonded or cemented prosthesis, multiple uni- or bimaxillary agenesia without remaining of deciduous teeth, restored by a fixed, bonded or cemented prosthesis or the partial adjacent prosthesis, multiple uni- or bimaxillary agenesia with remaining of deciduous teeth, restored by means of a supra-dental prosthesis. The first two situations have been described in dental literature and are relatively easy to treat. The same is not true for the third situation, where the decision to keep the temporary teeth considerably increases the difficulty of prosthetic restoration. This subject will be illustrated by the presentation of a clinical case of multiple bi-maxillary agenesia. The patient has: on the maxilla: an absence of 9 permanent teeth (18, 15, 14, 12, 22, 23, 24, 25, 28) and the presence of 4 deciduous teeth (62, 63, 64, 65), on the mandible: an absence of all permanent teeth, with the exception of 36 and 46, and the remaining of 4 deciduous teeth (75, 73, 83, 84). The remaining of deciduous teeth and the presence of a very high inter-arch space led to opting for dental coverage so as to keep the deciduous teeth and a proper vertical dimension. The patient wished to solve his "problem" in the maxilla first, and is not wanting to undergo the extraction of his deciduous teeth. The following therapeutic proposal was adapted: On the maxilla, a three-step procedure: first step: building of metal copings on 13, 16 and 26 and metal-ceramic crowns on 11 and 21, second step: building of telescop crowns on 16 and 26 and clasps on 13, 11 and 21, third step: casting of the removable partial denture framework and soldering to the telescop crowns and clasps. On the mandible, a provisional restoration using a supra dental resin removable partial denture with ceramic occlusal surfaces was adopted. The aesthetic and functional improvement, as well as the comfort provided to the patient due to this kind of mixed prosthesis, appeared to be satisfactory. PMID- 2200567 TI - [Surgical guide for prosthetic technic for Branemark osseointegrated implants]. AB - The goal of any prosthesis should be to restore the function of the masticatory system with occlusal stability and good esthetics. Even with fixtures, the prosthetic achievement must tend toward the final goal: the position of the prosthetic teeth. Therefore the prosthodontist must indicate to the surgeon the optimal sites for the fixtures. The link between the prosthetic team and the surgical team is the surgical template used not only during the installation of the fixtures, but also during the C.T. scan examination and for the localization of the fixtures after the healing period. The fabrication of the resin surgical template made from a wax up of the future restoration, with, if necessary, titanium rings at the location of the teeth necks, is presented in this article. This type of surgical guide is a versatile device allowing a better approach of the optimal prosthetic tooth localization all along the different periods of the surgical treatment. A better result is then obtained by the collaboration of the surgical and prosthetic teams, for the benefit of the patient. PMID- 2200569 TI - Nutritional factors in bovine gastrointestinal disease. AB - Gastrointestinal disorders may be prevented through proper nutrition. Attention should be placed on establishing optimum feeding programs for cattle in all stages of the life and production cycle. Normal reticuloruminal development in calves and maintenance of gastrointestinal function in adult cattle is dependent upon adequate nutrition. Nutrition is also an important part of therapy of many gastrointestinal disorders. PMID- 2200568 TI - [Cases of prosthodontic tissue reconditioning in geriatric dentistry]. AB - In elderly patients, recurrent fractures of the lower denture must raise the question of a neurological deficit as cause of the occluso-prosthetic imbalance. Hypotonicity of the peri-oral mastication musculature, especially the masseters, may explain the alteration of the prosthetic supporting surface due to shriveling of the mandibular arch, along with an osseogenesis at the point of flexion of the mandible. The rest and activity muscular imbalance, resulting from unilateral mastication, may cause lingual dysfunction and deviation of the tongue at rest. If this problem is not controlled within an acceptable period of time, one should expect psychological, biological and physiological consequences affecting the patient's physical condition. The restoration of the denture fracture is insufficient. Reconditioning must be performed in order to replace the existing prosthesis in the patient's function, allowing him/her to recover a normal psychological, biological and physiological balance. In conclusion, in geriatric dentistry, the objective of reconditioning is, not only to restore a functional occlusion, but also the psychological, biological and physiological balance of the patient. This is an unvaluable advantage, especially if this contributes to maintain or restore an often precarious health. PMID- 2200570 TI - Perioperative antimicrobial considerations for gastrointestinal surgery of cattle. AB - Perioperative use of antimicrobial drugs constitutes extra-label use of those drugs. Principles of therapeutic and prophylactic use of antimicrobial drugs can guide decisions about their perioperative use. Regimens currently suggested are based on those principles, theoretical information, pharmacokinetic and pharmacodynamic data, extrapolation from studies with other species, empirical data, personal bias, and experience. Controlled clinical investigations are necessary to provide objective data from which specific recommendations can be derived. PMID- 2200571 TI - Decision making in bovine abdominal surgery. AB - This article describes the signs, hematologic alterations, and methods of diagnosis of digestive disorders that may be treated surgically. The necessity for surgical intervention is analyzed, based on clinical experience and current knowledge. The prognosis for surgical correction of common digestive problems and prognostic indicators for abomasal volvulus are described. Decision analysis for digestive surgery is reviewed, with examples for abomasal displacement and volvulus. Preoperative preparation for abdominal surgery--including facilities, equipment, supportive therapy, and distinction between elective and emergency surgery--is discussed briefly. The four most common surgical approaches for abdominal surgery are reviewed, and their indications noted. PMID- 2200572 TI - Bovine esophageal surgery. AB - Esophageal disorders are relatively uncommon in cattle. The most frequently encountered problem is foreign-body obstruction, or choke. Other disorders may include perforation, rupture, stricture, diverticulum, and megaesophagus. Factors responsible for the high rate of complications associated with esophageal surgery include the lack of a serosal layer, movement during deglutition and reverse peristalsis, and an easily interrupted segmental blood supply. Important considerations of esophageal surgery include minimization of blood supply disruption, avoidance of transverse esophageal incisions whenever possible, provision of leak-proof closure of an incision or anastomosis and adequate drainage for the surrounding soft tissues, and restriction of postoperative oral alimentation and handling. PMID- 2200573 TI - Surgery of the bovine forestomach compartments. AB - Surgery of the forestomach compartments is performed in bovine practices for the diagnosis and treatment of many diseases, including traumatic reticuloperitonitis, perireticular abscess, vagal indigestion, and grain overload. Through a left flank laparotomy, the cranial abdomen is first explored by palpation for adhesions or masses. A rumenotomy allows thorough examination of the lumen of the rumen and reticulum. Surgical correction of disease may require emptying of the rumen, removal of a foreign body, or drainage of an abscess into the reticulum. With some abscesses, single aspiration and lavage of the abscess capsule or drainage of the abscess through the body wall, following a ventral celiotomy, is required. If adhesions associated with disease do not affect the innervation of the forestomach, the prognosis for return to functional status within the herd is good. Adhesions involving the medial wall of the reticulum or pericardial and myocardial disease due to extensions of traumatic reticuloperitonitis have a very poor prognosis, and thus slaughter should be considered in affected cases. PMID- 2200574 TI - Surgery of the bovine abomasum. AB - Intensive management of cattle has resulted in an increased incidence of abomasal disorders. Many of these disorders require surgical intervention for the best outcome. This article reviews the anatomy and physiology of the abomasum, abomasal disorders that may be treated by surgery, and the advantages and disadvantages of various surgical approaches to those disorders. PMID- 2200575 TI - Surgery of the bovine small intestine. AB - Cattle require surgery for small-intestinal problems less frequently than they do for abomasal, forestomach, or large-intestinal problems. Close attention to local vascular anatomy is critical to success when intestinal resection is required. Cows with signs of severe abdominal pain may make rapid recoveries following prompt surgical treatment. This article discusses relevant anatomy of the small intestine and the diagnosis and treatment of intussusception, volvulus, obstruction by incarceration or entrapment, and duodenal obstruction. PMID- 2200576 TI - Surgery of the bovine large intestine. AB - Cecal dilatation and volvulus are common entities in dairy cattle, whereas cecal torsion is not often encountered. These diseases have been related to excessive volatile fatty acid production. Obstruction of the remainder of the large colon may be simple or strangulating in nature. These obstructions are relatively rare. Clinical signs, surgical management, and surgical complications of diseases of the cecum and large intestine are discussed. PMID- 2200577 TI - Surgery of the neonatal bovine digestive tract. AB - Many disorders of the calf's gastrointestinal tract require surgical intervention if a successful outcome is to be obtained. The most common abnormalities in this category are abomasal volvulus, abomasal ulcers, small intestinal accidents, and atresia of the spiral colon. These can be differentiated by the age of the animal at presentation and a careful physical examination. Special considerations in neonatal gastrointestinal surgery include: ensuring adequate serum immunoglobulin status, rapid treatment of dehydration and hypoglycemia, and consideration of the inheritability of any corrected defects. Prompt attention to metabolic disturbances and correction of the abnormalities are essential for a successful outcome. PMID- 2200578 TI - Prevention and treatment of complications of bovine gastrointestinal surgery. AB - Abdominal surgery is the most common major surgical procedure performed by bovine practitioners. Most cattle, particularly dairy cattle, are sufficiently placid that major abdominal procedures are routinely completed with the animal standing, using local anesthesia and minimal physical and chemical restraint. An experienced bovine surgeon who exercises good judgment will infrequently encounter complications associated with this surgery. The purpose of this article is to describe the potential complications related to bovine abdominal surgery, how to avoid them, and how to treat them when they arise. PMID- 2200579 TI - Neoplasms of the bovine gastrointestinal tract. AB - Neoplasms of the bovine gastrointestinal tract are rare, possibly because of the low age of the sample population (slaughtered cattle). Forestomach neoplasia (papilloma/squamous cell carcinoma) has a high incidence in cattle from northern England and Scotland because of the mutagenic effects of bracken fern consumption and its interaction with BPV-4. Lymphosarcoma in the abomasum occurs in 41 per cent of cattle with lymphosarcoma, the most common bovine neoplasm in the United States. Small intestinal adenocarcinoma is associated with the papilloma/squamous cell carcinoma complex in the forestomach in England and Scotland, but occurs sporadically in other geographic locations. These lesions may be amenable to surgery, but death from metastatic disease occurs within 1 year. Neoplasms of the large intestine are rarely reported, but usually are adenocarcinoma. Adenoma and fibroma of the rectum may produce clinical signs of tenesmus and rectal prolapse. In general, neoplasia in cattle carries a poor prognosis because of early metastasis of adenocarcinoma and the high fatality of lymphosarcoma. Forestomach fibroma may be treated surgically with success, and palliative surgery for focal small intestinal tumors may be rewarding in individual cases. PMID- 2200580 TI - Heart valve surgery in the '90s: a surgeon's perspective. PMID- 2200582 TI - Metabolic effects of trichothecene T-2 toxin. AB - Cereals and other agricultural products contaminated with trichothecene mycotoxins are unfit for consumption. Until recently, the metabolic effects of T 2 toxin (T-2) were thought to reside in its ability to inhibit protein synthesis. It is now clear that trichothecenes have multiple effects, including inhibition of DNA, RNA, and protein synthesis in several cellular systems, inhibition of in vitro protein synthesis, inhibition of mitochondrial functions, effects on cell division, normal cell shape, and hemolysis of erythrocytes. It is argued that these effects are pleiotropic responses of the cell's biosynthetic network to protein synthesis inhibition. However, in studies with erythrocytes, which lack nuclei and protein synthesis, changes in cell shape and lytic response towards T 2 are observed. Susceptibility to lysis is species dependent and correlates with the presence of phosphatidylcholine. Owing to their amphipathic nature, T-2 and other trichothecenes could exert their cytotoxicity by acting on cell membranes. As for cell energetics, T-2 inhibits the mitochondrial electron transport system, with succinic dehydrogenase as one site of action. Although initial investigations of the metabolic effects of T-2 mediated cytotoxicity suggested the inhibition of protein synthesis as the principal site of action, current thought suggests that the effects of trichothecenes are much more diverse. PMID- 2200581 TI - The use of trichothecene-contaminated grains in feeds. AB - A review is presented describing the relative efficiencies of the various technologies that have been proposed to permit incorporation of mycotoxin contaminated grains into animal diets without adversely influencing growth rate or resulting in hazardous residues in edible animal tissues. When the degree of contamination is modest, it may be possible to dilute the contaminated materials with uncontaminated grain to lower the concentration of trichothecenes below the threshold of significant biological activity. A less useful alternative to dilution is the other mechanical approach of milling to remove the most heavily contaminated fractions of the grain. Chemical destruction of triochothecenes is also a possibility. An example is the use of sodium bisulfite treatment to destroy deoxynivalenol in contaminated corn. Such treatments may, however, reduce palatability and nutritional value. When the biochemical mechanism of trichothecene toxicity is known, in vivo therapeutic treatments may be possible. It has been shown, for example, that T-2 toxin-induced changes in brain prostaglandin production can be overcome by treatment with dexamethasone resulting in increased survival. A similar effect was seen using the selective platelet activating factor antagonist BN 52021. Another approach is the use of dietary treatments to either promote in vivo detoxification of mycotoxins or to reduce absorption from the digestive tract with the aid of nonnutritive binding agents. PMID- 2200583 TI - Alteration of immune function following dietary mycotoxin exposure. AB - Mycotoxins are a group of structurally diverse fungal secondary metabolites that elicit a wide spectrum of toxicologic effects. Of particular interest is the capacity of some mycotoxins to alter normal immune function when present in foods at levels below observable overt toxicity. Aflatoxin, patulin, citrinin, and zearalenone experimentally alter immunity, and recent evidence suggests that the immunologic effects of ochratoxin A and trichothecenes may have particular significance to human and animal health. For example, the capacity of ochratoxin A to inhibit natural killer cell activity and increase growth of transplantable tumour cells has been associated with renal and hepatic carcinomas in mice and might similarly contribute to human cancer. Impaired resistance to pathogenic microorganisms occurs after exposure to the trichothecenes T-2 toxin and vomitoxin. This may predispose food animals to infectious disease and could result in decreased productivity as well as increased animal-to-human transmission of pathogens such as Salmonella and Listeria. Vomitoxin also alters normal mucosal immune function, specifically at the level of regulation of development, differentiation, and homing of IgA-producing plasma cells. Interestingly, vomitoxin-induced enhancement of IgA production in the systemic compartment contributes to manifestations in the mouse that are highly analogous to human IgA nephropathy, the most common form of human glomerulonephritis worldwide. Over the long term, the extrapolation of mycotoxin-induced immunologic effects observed in inbred mice to actual disease in livestock and humans will require investigations that both simulate natural exposure conditions as well as improve understanding of the cellular and molecular bases for these effects among different species. PMID- 2200584 TI - Pancreatic glucagon secretion during a short period of hemorrhage in anesthetized dogs. AB - Glucagon has been implicated in the hormonal metabolic response to hemorrhage. However, evidence for this has been obtained largely from observations of circulating plasma glucagon concentration. A clear increase in the pancreatic glucagon secretion remains to be demonstrated. Plasma concentrations of pancreatic immunoreactive glucagon (IRG) and insulin (IRI) were determined in portal venous and aortic blood, and plasma glucose in aortic blood. Dogs were bled (approximately 15 mL/kg) until aortic systolic blood pressure dropped to approximately 50% (70.5 +/- 8.1 mmHg, n = 7) (1 mmHg = 133.32 Pa) of its control value (135 +/- 7.1 mmHg, n = 7), and the hemorrhagic hypotension was maintained for 10 min. The net portal venous IRG delivery rate rose significantly and continued to increase during the hemorrhagic hypotension despite a significant fall in the portal venous blood flow. Aortic IRG increased significantly along with the increase in portal venous IRG delivery rate (r = 0.838, n = 42, p less than 0.01). The portal venous delivery rate of IRI decreased significantly in response to hemorrhage. The aortic IRG/IRI concentration ratio increased significantly during the hemorrhage-induced hypotension. Aortic glucose concentration increased significantly 5 min after hemorrhage and continued to rise until the end of the hemorrhagic hypotension. The present study demonstrates that the secretion of pancreatic glucagon actually increases during the early phase of hemorrhage. The results also indicate that the increase in aortic IRG during the hemorrhagic hypotension is due to the increased pancreatic glucagon secretion. It is suggested that the pancreatic glucagon may be involved in the early hyperglycemic response to hemorrhage. PMID- 2200585 TI - Stable isotopes in nutrition research: historical perspective and overview. PMID- 2200586 TI - Inaccuracies in self-reported intake identified by comparison with the doubly labelled water method. AB - To test the accuracy of self-reported energy intake, reported intake was compared with measured energy expenditure. Results from nine studies were reviewed in which intake data were obtained by recall or weighed record for at least 7 days. Expenditure was measured for 7 days or more by the doubly labelled water method. Individual differences between reported intake and expenditure were large (range +25 to -76%). Group mean differences were smaller. Lean, nonathletic groups living in industrialized countries demonstrated the smallest mean difference between self-reported energy intakes and expenditure (0 to -20%). Obese populations demonstrated the largest mean differences (-35 and -50%), but women living in the Gambia and elite athletes also demonstrated large mean differences. Most of the difference appears to be due to under-reporting, but some subjects lost weight during the reporting period indicating that some of the difference was due to undereating. Because the greatest bias was observed in obese subjects, current methods for self-reported energy intake are not recommended for use in obesity research. PMID- 2200587 TI - Stable isotopes in the management and diagnosis of inborn errors of metabolism. AB - Stable isotope techniques offer advantages over older methods in safety, sensitivity, specificity, and reduction in number of subjects required for analytic determinations in some types of studies in "inborn errors of metabolism." In addition to their use as internal standards for gas chromatography - mass spectrometry, quantitation of plasma substrates, and their urinary metabolites, stable isotopes have been successfully employed in studies of metabolite identification, enzyme activity, nutrient turnover and requirements, and diagnosis of inborn errors of metabolism. PMID- 2200588 TI - Use of deuterated water for measurement of short-term cholesterol synthesis in humans. AB - Previous methods for measurement of cholesterol synthesis de novo in humans have either required extended measurement periods or been indirect. Recently, a technique based on the rate of incorporation of deuterium from D2O into the plasma cholesterol pool has been developed. Following oral ingestion of D2O, deuterium enrichment over time in free plasma cholesterol after combustion and reduction was determined using isotope ratio mass spectrometry. This methodology enabled direct measurement of plasma cholesterol synthesis over intervals as short as 4 h. The technique has been used to demonstrate changes in synthetic rate in response to feeding conditions and genetic influences. Fasting over 36 h resulted in markedly reduced deuterium uptake into cholesterol in healthy males. Diurnal variations in synthetic rate have also been identified, with elevated synthesis observed during nocturnal periods in both fed and fasted subjects. In addition, the influence of apolipoprotein E phenotype on cholesterol synthesis has been shown using this technique. Individuals carrying the apoprotein epsilon 2 allele demonstrated lower synthesis compared with those possessing the epsilon 4 allele. Thus, the deuterium incorporation technique for measuring cholesterol synthesis demonstrates potential as a valuable stable isotope method for human nutrition studies. PMID- 2200589 TI - Isotope fractionation by plants and animals: implications for nutrition research. AB - The isotopic compositions of animal tissues, minerals, and fluids reflect those of ingested food and water and inhaled gases. This relationship is illustrated by a review of data pertaining to five light elements of biological interest (carbon, nitrogen, hydrogen, oxygen, and sulphur). Processes affecting the isotopic composition of inorganic compounds in reservoirs are summarized, and isotope fractionation during transfer of elements from these inorganic reservoirs through progressive trophic levels of food webs is discussed. Variability of delta values within and among individuals, populations, and species of plants and animals is attributed to at least six factors: locality, dietary selectivity, biochemical composition of food, isotope effects in metabolic processes, turnover rates, and stress. Features of a variety of terrestrial and aquatic ecosystems are used to illustrate basic concepts. Future research should seek to clarify specific mechanisms affecting delta values during the transfer of elements through food webs. PMID- 2200590 TI - Mycotoxins in the food chain: nutritional and toxicological considerations. PMID- 2200591 TI - Mycotoxins and toxigenic fungi on cereal grains in western Canada. AB - Toxins occasionally present on cereal grains in the field in western Canada include ergot alkaloids produced by Claviceps purpurea and trichothecenes produced by Fusarium species, particularly Fusarium sporotrichiodes and Fusarium graminearum. HT-2 toxin, T-2 toxin, diacetoxyscirpenol, and deoxynivalenol are the main trichothecenes encountered. During storage of cereals, the predominant toxins and toxigenic fungi are ochratoxin A and citrinin produced by Penicillium aurantiogriseum, P. chrysogenum, and P. verrucosum and sterigmatocystin produced by Aspergillus versicolor. The incidence of toxin-contaminated grains is extremely low relative to the volume of grains produced. Occurrence of toxins is influenced by field moisture, temperature, and bin storage conditions of a particular year. The risk of toxin production is highest in durum wheat and lowest in oats. PMID- 2200592 TI - Mycotoxicoses of domestic animals and their diagnosis. AB - Mycotoxins have been named "agents in search of a disease," and the considerable progress in analytical methodology over the last 10 years has not changed this very much. The following are factors that contribute to the difficulty of making a diagnosis: (1) nonspecificity of lesions; (2) masking of mycotoxic effects by secondary effects, e.g., through immunosuppression; (3) late appearance of a lesion, e.g., bone marrow damage or neoplasia; (4) interaction of several mycotoxins or presence of other toxicants or deficiency states; (5) species variation in the response to the mycotoxin(s); (6) difficulty of linking a late appearing effect with a demonstrable cause; (7) low doses of mycotoxins may cause stimulating effects; and (8) not being aware of the potential of a mycotoxin as a causative factor in disease. The mycotoxins of major importance in Canada are trichothecenes, ochratoxin, zearalenone, and ergot. It is concluded that the significance of mycotoxins for animals in Canada is likely generally underestimated. PMID- 2200593 TI - Ochratoxin A: an important western Canadian storage mycotoxin. AB - Ochratoxin A (OA) is a mycotoxin produced by certain species of storage fungi of the Penicillium and Aspergillus genera. Toxin production by these fungi is influenced by species and even strain of fungi, time and temperature of incubation, moisture content of substrate, and type of substrate. OA has been shown to occur in various grains, cereals and other plant products, animal feeds, meats, and human tissues in countries throughout the world. Of interest is the discovery of OA in a high percentage of blood from humans in Germany. OA is acutely toxic to many different animals and in addition to being a nephrotoxin, it is a hepatotoxin, a teratogen, a very potent carcinogen, possibly a mutagen, and an immunosuppressive agent. OA is rapidly absorbed throughout the entire gastrointestinal tract and distributes itself in the body as a two-compartment open model and has a particular high affinity for serum albumin. OA is hydrolyzed by the intestinal microflora into nontoxic compounds (7-carboxy-5-chloro-8 hydroxy-3,4-dihydro-3R-methylisocoumarin (O alpha) and phenylalanine). It is excreted as either OA, hydroxylated OA, or O alpha in both the urine and feces. OA appears to exert its toxic effect by promoting an increased level of lipid peroxidation, by inhibition of an amino acylation reaction, and possibly by conversion into metabolites that are capable of binding DNA. These in turn cause other secondary effects associated with OA. It would appear that this compound presents a true potential hazard for humans as its occurrence is wide spread and it is highly carcinogenic. PMID- 2200594 TI - Kinematic analysis of limb movements in neuropsychological research: subtle deficits and recovery of function. AB - In this brief review, we argue that a detailed analysis of the spatial and temporal characteristics of visually guided limb movements can provide important insights into the nature of neuropsychological deficits and the functional organization of the brain. In particular, we will show how kinematic analysis of a simple aiming movement can reveal differences that might not be apparent clinically in the behaviour of patients with unilateral brain lesions. We will argue that the subtle but distinctive deficits that follow damage to the left or right hemisphere can be related to the clinical syndromes of manual apraxia and hemispatial neglect, respectively. The fact that these deficits are apparent only with kinematic analysis demonstrates the potential of these techniques for evaluating recovery of function. PMID- 2200595 TI - The relationship of structural ischemic brain damage to neurobehavioural deficit: the effect of postischemic MK-801. AB - Global cerebral ischemia is well known to cause neuronal necrosis in selectively vulnerable sectors of the hippocampus. Since the hippocampus of the rat is involved in spatial navigation, learning, and memory, selective deficits in these abilities may arise from ischemic brain damage. Previous studies have shown (a) a detectable neurobehavioural deficit due to ischemic brain damage limited to half of the CA1 sector of the hippocampus and (b) a reduction of ischemic neuronal necrosis with the noncompetitive N-methyl-D-Aspartate (NMDA) antagonist MK-801. This study was designed to determine the relationship between the improvement in structural brain damage in postischemically treated rats and any improvement in neurobehavioural performance, using a learning-set water task. Seventeen male Wistar rats received 10.5 min of forebrain ischemia induced by carotid clamping and hypotension. Brain temperature was estimated with probes in the temporalis muscle. Ten of these animals received no therapy (controls), and seven animals received 5 mg/kg MK-801 iv, 20 min postischemia. Six additional rats underwent a sham operation. Postischemic hypothermia was prevented with heating lamps. Four controls and one MK-801 treated animal died. The survivors were then tested on a place learning-set task in a swimming pool paradigm, and quantitative histopathologic analysis of their entire brains was done. The learning-set task revealed defects in spatial navigation, reflected as increased errors and latency in the performance of the untreated control rats. The performance of the MK-801 treated group progressively approached that of sham-operated rats over the course of testing and was significantly better than controls. Importantly, no long-term detrimental effect of MK-801 on the learning-set task performance was seen. Quantitative neuropathology revealed significantly less damage in the MK-801 treated group in all major brain regions. In the hippocampus, MK-801 treated animals showed hippocampal damage limited to the vulnerable portion of the pyramidal cell band comprising 48.8% of the CA1 pyramidal cells, as opposed to 72.4% in untreated controls. Extra-hippocampal damage was evident only in untreated control animals. MK-801 totally prevented neuronal necrosis in both the cerebral cortex and striatum and also prevented infarction in the neocortex and thalamus. Three conclusions emerge from the study. First, postischemic MK-801 mitigates structural brain damage in several brain regions in the absence of concomitant hypothermia. Second, neurobehavioural performance appears to be improved by MK-801 when performance trends are examined, but is somewhat less sensitive than quantitated histopathology due to compounding interanimal variation in performance abilities.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2200596 TI - Adrenal medulla graft induced recovery of function in an animal model of Parkinson's disease: possible mechanisms of action. AB - Following unilateral dopamine (DA) denervation of the striatum in animals, there is an asymmetry in the striatal DA system. Animals with such denervations will rotate vigorously when given dopaminergic drugs. Adrenal medulla grafts placed in the lateral ventricle adjacent to a DA-denervated striatum decrease rotational behaviour induced by DA receptor agonists or DA-releasing agents. This discussion reviews research on the use of adrenal medulla grafts to reverse behavioural deficits following DA-denervation of the striatum. Results from basic animal research and from the application of the procedure to patients with Parkinson's disease suggests that at least three different fundamental processes may mediate the functional effects of adrenal medulla grafts: (a) Adrenal medulla grafts may induce changes in the blood-brain barrier; (b) adrenal medulla grafts may induce an increase in serum DA; and (c) adrenal medulla grafts may have a trophic effect on the host brain. Hypotheses are proposed to explain the behavioural effects of adrenal medulla grafts in light of the processes that are thought to mediate their effects. PMID- 2200597 TI - Preoperative radiotherapy for adenocarcinoma of the rectum. AB - Curative surgery remains the principal treatment for rectal carcinoma. Unfortunately failure following surgery, particularly through local recurrence, is an all too common event. Among the potential adjuvant therapies, preoperative radiotherapy holds clear promise. A review of the clinical trials evaluating this treatment modality shows that it can decrease the rate of local recurrence and may even improve the overall 5-year survival. Preoperative radiotherapy is consistently well tolerated up to doses as high as 60 Gy; it does not complicate the surgical resection or increase the perioperative morbidity and mortality. Preoperative radiotherapy warrants further investigation to select those patients who are most likely to benefit from it. PMID- 2200598 TI - Nonparasitic splenic cysts: a case report and review. AB - Cysts of the spleen are rare but usually benign. The authors describe the case of a young woman with a splenic cyst who underwent splenectomy. Ultrasonography and computed tomography have helped improve the preoperative diagnosis of nonparasitic splenic cysts, and as the use of ultrasonography increases, so will the finding of incidental splenic cysts. Whether all splenic cysts enlarge is unknown, and it is uncertain whether all small asymptomatic cysts need treatment. The cysts may enlarge, become infected or rupture. Total splenectomy has been the most common treatment in the past, but, because of the risk of postsplenectomy sepsis, partial splenectomy may be preferred when technically possible. PMID- 2200599 TI - Edinburgh is synonymous with medical history. PMID- 2200600 TI - New drugs for hypertension: should data precede conclusions? PMID- 2200601 TI - Periodic health examination, 1990 update: 3. Interventions to prevent lung cancer other than smoking cessation. Canadian Task Force on the Periodic Health Examination. PMID- 2200602 TI - A technique for computer-guided stereotaxis without preoperative head fixation. AB - A CT-guided stereotactic method is described which uses a standard BRW frame for probe insertion but which does not require frame fixation to the skull during the localizing scan. The patient is instead scanned wearing three radiopaque scalp markers, and new software utilized to obtain BRW coordinates. Acceptable accuracy for targets greater than one centimeter in diameter was obtained in phantom trials and in three case reports. This technique may be helpful for stereotactic targets greater than one centimeter in diameter and when preoperative head fixation is not desirable or possible. PMID- 2200604 TI - Statistical methods in microbiology. AB - Statistical methodology is viewed by the average laboratory scientist, or physician, sometimes with fear and trepidation, occasionally with loathing, and seldom with fondness. Statistics may never be loved by the medical community, but it does not have to be hated by them. It is true that statistical science is sometimes highly mathematical, always philosophical, and occasionally obtuse, but for the majority of medical studies it can be made palatable. The goal of this article has been to outline a finite set of methods of analysis that investigators should choose based on the nature of the variable being studied and the design of the experiment. The reader is encouraged to seek the advice of a professional statistician when there is any doubt about the appropriate method of analysis. A statistician can also help the investigator with problems that have nothing to do with statistical tests, such as quality control, choice of response variable and comparison groups, randomization, and blinding of assessment of response variables. PMID- 2200603 TI - Lectins and their application to clinical microbiology. AB - Lectins are generally associated with plant or animal components, selectively bind carbohydrates, and interact with procaryotic and eucaryotic cells. Lectins have various specificities that are associated with their ability to interact with acetylaminocarbohydrates, aminocarbohydrates, sialic acids, hexoses, pentoses, and as other carbohydrates. Microbial surfaces generally contain many of the sugar residues that react with lectins. Lectins are presently used in the clinical laboratory to type blood cells and are used in a wide spectrum of applications, including, in part, as carriers of chemotherapeutic agents, as mitogens, for fractionation of animal cells, and for investigations of cellular surfaces. Numerous studies have shown that lectins can be used to identify rapidly certain microorganisms isolated from a clinical specimen or directly in a clinical specimen. Lectins have been demonstrated to be important diagnostic reagents in the major realms of clinical microbiology. Thus, they have been applied in bacteriology, mycology, mycobacteriology, and virology for the identification and/or differentiation of various microorganisms. Lectins have been used successfully as epidemiologic as well as taxonomic markers of specific microorganisms. Lectins provide the clinical microbiologist with cost-effective and potential diagnostic reagents. This review describes the applications of lectins in clinical microbiology. PMID- 2200607 TI - Hydrocephalus--revision of its definition and classification with special reference to "intractable infantile hydrocephalus". AB - With the advent of computed tomography (CT) scan, much information has been obtained about the pathophysiology of hydrocephalus. It is now clear that hydrocephalus is not a disease entity but rather a syndrome or sign resulting from disturbances in the dynamics of cerebralspinal fluid (CSF) caused by various diseases. Consequently, it has become necessary to revise its definition and classification. In this paper, a contemporary definition and classification of hydrocephalus are presented. Also, a classification of "intractable hydrocephalus"--with its diagnostic criteria--which is a clinically unsolved problem, is attempted, bearing in mind its place in the clinical management and future investigation of the pathophysiology of hydrocephalus. PMID- 2200605 TI - Serology of coccidioidomycosis. AB - Serologic tests have assisted in the diagnosis and prognosis of coccidioidomycosis for a half-century. The causative agent, Coccidioides immitis, is a dimorphic fungus existing in a hyphal form with arthroconidia in nature and in the usual culture. The arthroconidia represent the inhaled infective forms which in vivo and under special laboratory conditions form spherules which endosporulate. The culture filtrate/autolysate (coccidioidin) from the hyphal phase has provided antigens of suitable reliability for currently used serologic tests. These tests are primarily to determine the two major antibody responses: the early immunoglobulin M (IgM) response is useful in the diagnosis of acute primary coccidioidomycosis. Later, IgG is produced and usually outlasts the IgM, persisting in chronic coccidioidomycosis. The IgM is detectable by tube precipitin, a corresponding immunodiffusion, or latex particle agglutination tests. The pertinent antigen(s) is heat stable and pronase resistant and appears to be largely carbohydrate, mainly mannose with some 3-O-methyl mannose. The IgG detectable in the serum and other body fluids by complement fixation and a corresponding immuno-diffusion is useful in diagnosis, and its quantitation provides an indicator of progression of disease (increasing titer) or regression (decreasing titer). The pertinent antigen appears to be a heat-labile, pronase sensitive protein which in an unreduced form has a molecular weight of 110,000. A third very useful serologic procedure is the exoantigen test for identification of putative cultures of C. immitis. PMID- 2200606 TI - Quantitative aspects of septicemia. AB - For years, quantitative blood cultures found only limited use as aids in the diagnosis and management of septic patients because the available methods were cumbersome, labor intensive, and practical only for relatively small volumes of blood. The development and subsequent commercial availability of lysis centrifugation direct plating methods for blood cultures have addressed many of the shortcomings of the older methods. The lysis-centrifugation method has demonstrated good performance relative to broth-based blood culture methods. As a result, quantitative blood cultures have found widespread use in clinical microbiology laboratories. Most episodes of clinical significant bacteremia in adults are characterized by low numbers of bacteria per milliliter of blood. In children, the magnitude of bacteremia is generally much higher, with the highest numbers of bacteria found in the blood of septic neonates. The magnitude of bacteremia correlates with the severity of disease in children and with mortality rates in adults, but other factors play more important roles in determining the patient's outcome. Serial quantitative blood cultures have been used to monitor the in vivo efficacy of antibiotic therapy in patients with slowly resolving sepsis, such as disseminated Mycobacterium avium-M. intracellulare complex infections. Quantitative blood culture methods were used in early studies of bacterial endocarditis, and the results significantly contributed to our understanding of the pathophysiology of this disease. Comparison of paired quantitative blood cultures obtained from a peripheral vein and the central venous catheter has been used to help identify patients with catheter-related sepsis and is the only method that does not require removal of the catheter to establish the diagnosis. Quantitation of bacteria in the blood can also help distinguish contaminated from truly positive blood cultures; however, no quantitative criteria can invariably differentiate contamination from bacteremia. PMID- 2200608 TI - Tethered-cord syndrome after repair of meningomyelocele. AB - The occurrence of tethered-cord syndrome is one of the delayed consequences of the repair of meningo-myelocele. The existing neurological deficit worsens, or a new deficit is superimposed on the existing one. In addition, urological and orthopedic symptoms are also frequently encountered. Although radiological studies may be suggestive of tethering of the cord, not all children are symptomatic. Magnetic resonance imaging is the best radiologic study available. Ultrasonography, although economical and easy to perform, does not yield an optimal image. It appears that a careful periodic clinical evaluation is the best way to evaluate the patients for surgery. PMID- 2200609 TI - Ventral brain-stem compression from a subarachnoid ependymal cyst. AB - A case of ventral brain-stem compression by a congenital subarachnoid ependymal cyst in an infant is presented. Marsupialization of the cyst provided effective decompression and clinical improvement. Immunohistochemical staining demonstrated the glial nature of the epithelium. The fact that these cysts may be congenital, as demonstrated here, supports the hypothesis that they arise from glial elements that have been displaced during development. PMID- 2200610 TI - Transient focal leukoencephalopathy following intraventricular methotrexate and cytarabine. A complication of the Ommaya reservoir: case report and review of the literature. AB - A 14-year-old boy, suffering from acute lymphoblastic leukemia with meningeal involvement, was treated with intraventricular methotrexate and cytosine arabinoside, administered via an Ommaya reservoir (OR). Three months later, right occipital headache, vomiting, and lethargy appeared. Cerebrospinal fluid specimens showed increased proteins and a right frontal slow-wave focus was evident on the EEG recording. The computed tomography scan revealed white matter hypodensity within the right frontal and rolandic regions. After injection of medium contrast, an abscesslike hyperdensity appeared, surrounding both a well placed cannula tip and the right frontal horn of the lateral ventricle. Brain swelling and shift signs were also evident. Nine cases of focal methotrexate leukoencephalopathy have been previously reported, and in six of these there was a misplaced OR cannula tip. The focal methotrexate leukoencephalopathy seems to be related to the neurotoxicity of the drugs administered, and may also exist with a well-placed OR cannula tip. Immediate removal of the catheter may be associated with a benign evolution. PMID- 2200611 TI - Effects of substrata on the polarization of bovine endometrial epithelial cells in vitro. AB - Epithelial-cell function requires cellular polarity in which apical membrane surfaces have unique characteristics and cellular organelles are stratified. Physiological investigations of endometrial epithelial cells would be enhanced greatly by the ability of a method to polarize cells in culture. This study investigates the effects of different substrata on polarization of cultured bovine endometrial epithelial cells. Fetal bovine endometrial epithelial-cell lines were developed from explant outgrowth. Epithelial monolayers were subcultured onto amniotic membranes, Millicell-HA membranes, or Millicell-CM membranes coated with rat-tail collagen, Matrigel, laminin, Vitrogen, or fibronectin. Cultures on these substrata were maintained at the air/liquid interface. Cells grown on either collagen-coated or uncoated Millicell membranes also were maintained submerged in medium. Excellent polarized morphology was attained in cultures grown at the air/liquid interface on amniotic membranes and rat-tail collagen-coated membranes. Lectin-binding patterns to apical membranes of polarized epithelial cell cultures paralleled patterns of binding to bovine endometrial surfaces in vivo. Cultures on rat-tail collagen were maintained for several weeks. These methods provide a valuable system for studying the endometrium in vitro. PMID- 2200613 TI - Subperiosteal implants. PMID- 2200614 TI - Expression of human immunodeficiency virus long terminal repeat in the human promonocyte cell line U937: effect of endotoxin and cytokines. AB - Phagocytic macrophages are known to support noncytopathic, chronic infections of human immunodeficiency virus (HIV). Regulation of viral replication in such cells with either chronic low-grade or latent HIV infection is probably influenced by both viral and cellular factors acting on the viral long terminal repeat (LTR). This study identifies naturally occurring biological response modifiers which are able to affect the HIV-LTR linked to the chloramphenicol acetyl transferase (LTR CAT) gene in a stable transfection of the human promonocyte cell line, U937, in the absence of other viral proteins. In this model system, endotoxin lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) are able to independently stimulate expression of LTR-CAT. Granulocyte/macrophage-colony stimulating factor can enhance the effect of TNF-alpha or LPS, but other cytokines tested had minimal or no effect on LTR-CAT. In addition to effects on cellular susceptibility and immune function, the ability of naturally occurring factors to affect HIV-LTR in its integrated state may have particular relevance to progression of active disease from latent infection. PMID- 2200615 TI - [Study of LDL receptor activity of lymphocyte by immunofluorescence method]. AB - Fluorescein-isothiocyanate (FITC) labeled anti-LDL-IgG was used to demonstrate LDL bound with lymphocytes. The activity of LDL receptor was expressed by the fluorescence intensity of individual cell (receptor-ligand immunofluorescence method). With this method the effect of dietary cholesterol on LDL receptor activity of lymphocytes was studied. The results showed that with the elevation of plasma cholesterol, the fluorescence intensity of individual cell and the percentage of labelled cell were decreased. i.e. the LDL receptor activity was reduced due to hypercholesterolemia, and lowering of plasma cholesterol level might be accompanied with restoration of the LDL receptor activity. These results suggest that inhibition of LDL receptor activity in patients with non-familial hypercholesterolemia can be recovered by decreasing plasma cholesterol level. PMID- 2200612 TI - Thrombospondin expression in traumatized skeletal muscle. Correlation of appearance with post-trauma regeneration. AB - Biochemical and immuno-microscopic techniques were used to study temporal involvement of thrombospondin in relation to fibrinogen in muscle regeneration using a rat skeletal muscle-wound model. In undamaged control muscle, no fibrinogen and minimal thrombospondin antigen was found. Following crushing injury, fibrin networks appear immediately, followed by a gradual ordered accumulation of thrombospondin (within a few hours) in the vicinity of the vascular bed and adjacent endomysial connective tissue. Later, thrombospondin becomes associated with connective tissue and basal laminae around muscle fibers throughout the damaged muscle, maximal labelling occurring 3-6 days post-injury. Thrombospondin immunoreactivity decreased thereafter to near normal levels after 7 days post-injury, coincident with the appearance of regenerating muscle fibers. In contrast, little fibrin material remained by five days after injury. Quantitative radioimmunoassay of soluble thrombospondin antigen and radioimmune labelling of thick frozen sections reinforced the qualitative immuno-microscopic observations, with levels peaking at 3-4 days post-trauma, 10-fold over control levels. SDS-PAGE immunoblotting of non-reduced muscle extracts three days after a crush assault shows that the bulk of the thrombospondin incorporated into the injury site exists in a polymerized state (less than or equal to 1000 kD). These results demonstrate that the temporal appearance and disappearance of thrombospondin in the healing of a crushing lesion in muscle is related more closely to the regeneration phase of muscle than to the coagulation phase. PMID- 2200617 TI - [Application of morphometry to pathology]. PMID- 2200616 TI - [A pathological study on 662 autopsy cases of chronic cor pulmonale. The National Pathological Cooperative Group of Cor Pulmonale]. AB - According to the unified diagnostic criteria and methods, 662 cases of cor pulmonale autopsy were accepted and the acceptable rate was 88.5%. Additionally, a data base with IBM PC/XT computer and dBASE-III was established in which the data of all cases accepted were stored, processed and analyzed. The results showed that chronic bronchitis and emphysema were the primary pulmonary diseases of chronic cor pulmonale in China. Chronic bronchiolitis and peribronchiolitis were considered as the late stage of bronchitis causing damage to lung tissues and constituting the central link of such complications as pulmonary hypertension and right ventricular hypertrophy. The authors emphasize also that the cellular elements and extracellular matrix were the major reason in decreasing pulmonary vascular compliance, while dilation of the lumen of pulmonary small arteries was probably the secondary change of pulmonary hypertension. According to the results obtained, it is considered that hypertrophy of the supraventricular crest can be used as one of the diagnostic criteria of right ventricular hypertrophy due to pulmonary hypertension. PMID- 2200618 TI - Use of a new simplified assay for phospholipase A2 to measure bacterial enzyme levels. AB - During investigation of possible phospholipase A2 (PLA2) production by pathogenic bacteria associated with preterm labour, a rapid and simple assay method was developed which involved few steps and which could be applied easily to large numbers of samples. The principle difference from previously described methods lies in separation of the reaction products by partitioning them between organic and aqueous solvents, rather than by using thin layer chromatography. This enabled us to determine that none of the bacteria studied released PLA2 into the culture medium spontaneously, and that only Escherichia coli contained high levels of PLA2. PMID- 2200619 TI - Radioimmunoassay may overestimate insulin in non-insulin-dependent diabetics. AB - We have compared insulin concentrations measured by radioimmunoassay (RIA) in plasma from 50 fasting non-insulin-dependent diabetics (NIDDM) with those measured by a new monoclonal antibody-based two-site immunoradiometric assay (IRMA) of insulin (which has no significant cross-reaction with proinsulin-like molecules). We find that the RIA measures the sum of the insulin and proinsulin like molecules and that the IRMA insulin concentrations are 38% of those measured by the RIA in those diabetic subjects. We conclude that the importance of insulin deficiency in NIDDM may have been obscured by this error. PMID- 2200620 TI - Clinical and biochemical effects of incremental doses of the long-acting somatostatin analogue SMS 201-995 in ten acromegalic patients. AB - Ten patients (seven women, three men) with active acromegaly, five previously treated and five newly diagnosed, were included in an open-label prospective trial of 3 daily subcutaneous injections of the long-acting somatostatin analogue SMS 201-995 (Sandostatin) at increasing doses in order to obtain maximum growth hormone (GH) suppression. Four patients had received surgery, radiotherapy or bromocriptine. SMS 201-995 doses were increased in a stepwise fashion from 100 micrograms every 8 h (three times daily) to 200, 300 and finally 500 micrograms three times daily at monthly intervals if mean serum GH values failed to decrease to undetectable levels in over 75% of the samples. The optimal dose was maintained for up to 28 months. Significant clinical improvement of headache, soft tissue swelling, facial features, hyperhidrosis and paraesthesia occurred in all patients. Mean 12-h GH levels were significantly suppressed in four patients and fell to normal values in four. Suppression of GH levels was not achieved in two patients. Comparison of the mean interindividual GH values shows that the optimal efficacious dose is 100 micrograms t.i.d. in 7/10 patients. Somatomedin-C (SM-C) was also significantly reduced to below 50% of pretreatment levels in nine patients in whom it was measured. The subsequent increments of SMS 201-995 up to 500 micrograms three times daily did not produce further clinically relevant GH or SM-C suppression. Pituitary tumour shrinkage occurred in five patients. Thyroid function remained normal. Impaired glucose tolerance occurred in four patients. Side-effects (diarrhoea, abdominal discomfort) were mild and transient. Asymptomatic gallstones occurred in three patients on 1500 micrograms/day and one patient on 600 micrograms/day after 6-12 months treatment. This dose-finding study shows that 100 micrograms three times daily SMS 201-995 is an effective therapy for most of the acromegalic patients we treated. PMID- 2200621 TI - Familial acromegaly: studies in three families. AB - Acromegaly is usually regarded as a disease which arises sporadically except on those rare occasions in which it occurs as one component of an inherited pluriglandular syndrome. Familial acromegaly occurring in isolation has been reported only rarely. We have studied three families in each of which two first degree relatives have developed acromegaly without clinical evidence of other endocrinopathies, in order to clarify the relationship of familial acromegaly to multiple endocrine neoplasia, type 1 (MEN 1). No further subclinical cases of acromegaly have been detected in those first-degree relatives of the index cases who were screened. In two of the families, we have found no evidence of abnormal pancreatic or parathyroid function either in the acromegalic index cases or their asymptomatic relatives: a diagnosis of MEN 1 is therefore effectively excluded. In the third family, the presence of multiple subcutaneous lipomata in several members of the family and elevation of PTH levels in two (normocalcaemic) acromegalic index cases, might indicate a highly atypical presentation of MEN 1. None of the six acromegalic index cases had elevations of circulating growth hormone releasing hormone levels. We conclude that isolated familial acromegaly may be more common than has hitherto been realized and that, in these families at least, ectopic production of growth hormone releasing hormone is not responsible. PMID- 2200622 TI - A comparative study of single-dose growth hormone therapy as an adjuvant to gonadotrophin treatment for ovulation induction. AB - One intramuscular injection of biosynthetic human growth hormone (24 IU), administered on the first day of gonadotrophin treatment for ovulation induction, significantly augmented the ovarian response to gonadotrophic stimulation in seven patients. Compared with a protocol involving six injections of 24 IU of GH given on alternate days to the same patients, the smaller dose had an intermediate but highly significant effect in reducing the amount, duration of treatment and daily effective dose of hMG needed to induce ovulation. The difference between the effect of the one-dose and six-dose protocols was small. The action of growth hormone on the human ovary, probably mediated by insulin like growth factor-1 (IGF-1), appears effective in enhancing the response to gonadotrophin therapy even when given in a single dose. PMID- 2200623 TI - The effects of improved blood glucose on growth hormone and cortisol secretion in insulin-dependent diabetes mellitus. AB - Growth hormone and cortisol secretion were studied in 25 patients with insulin dependent diabetes before (Study 1) and 2 weeks after improved glucoregulation (Study 2). Blood samples for serum growth hormone (GH) and blood glucose determination were collected at hourly intervals whilst blood samples for cortisol and C-peptide were collected every 6 h during the 24-h period in Study 1 and Study 2. Glycaemic control was significantly improved in Study 2 compared to that in Study 1 (8.5 vs 13.3 mmol/l; P less than 0.001). With improved control, growth hormone levels rose by 21% (5.7 vs 4.7 mU/l; P less than 0.05). Throughout both study periods growth hormone levels were higher in patients with no residual C-peptide secretion (10 CpN patients) compared with patients with residual beta cell function (15 CpP patients) (7.1 vs 3.2 mU/l in Study 1; 8.9 vs 4.2 mU/l in Study 2; P less than 0.001). Characteristic shapes of the 24-h blood glucose profile curves during both study periods were significantly different between the CpN and CpP group. Plasma cortisol decreased in both groups with improved metabolic control (P less than 0.001) but the observed different diurnal pattern did not change. These results demonstrate the importance of residual endogenous insulin secretion in determining growth hormone secretion in insulin-dependent diabetes and have important implications for glycaemic control and risk of microvascular complications. PMID- 2200625 TI - Robinow syndrome: report of two patients with cystic kidney disease. AB - Two patients with Robinow syndrome and cystic kidney disease are described. We propose that this anomaly should be added to the spectrum of malformations associated with the syndrome. PMID- 2200624 TI - Intragenic deletions in 164 boys with Duchenne muscular dystrophy (DMD) studied with dystrophin cDNA. AB - DNA from 164 unrelated Duchenne muscular dystrophy patients was screened with cDNA probes from the dystrophin gene. Molecular deletions were demonstrated in 82 (50%) subjects. Sixty-two deletions (76%) were detected using cDNA probes Cf56a (cDNA 8) and Cf56b (cDNA 6-7) which map to the centre of the gene, while 22 deletions (27%) mapped to the 5' end of the gene. In three subjects, the deletion extended from the 5' end to the centre of the gene. One deletion was identified by probe 47-4 (cDNA 5b-7) alone. In six of the deletions, junction fragments of altered size were observed. Using the three cDNA probes, RW2kb, Cf56a (cDNA 8) and Cf56b (cDNA 6-7), 99% of the deletions were detected. This will have implications for prenatal diagnosis in deletion families. Unlike Becker muscular dystrophy, where the deletions are more homogeneous, the deletions in the present study were heterogeneous both in size and position. No correlation between intelligence and either site or extent of deletion was found. PMID- 2200626 TI - Low-dose captopril scintigraphy in the evaluation of renovascular hypertension. AB - This study compared the results of renal scintigraphy with simultaneous administration of Tc-99m DTPA and I-131 Hippuran (before and after 25 mg of oral captopril) with the results of the renal arteriogram and renal vein renins (before and after the administration of 25 mg of oral captopril) to evaluate the sensitivity and specificity of renal scintigraphy in the diagnosis of renovascular hypertension. The results of 21 consecutive patients suspected of having renovascular hypertension who underwent scintigraphy and renal arteriography were analyzed. Renal scintigraphy postcaptopril detected all the cases of renovascular hypertension (eight patients) plus two additional patients who had significant renovascular stenosis but no renin overproduction. The results indicate that the renal scintigram, before and after the administration of captopril, is an accurate and sensitive test for the detection of renovascular hypertension and should be used as a screening procedure before arteriography is considered. PMID- 2200628 TI - Torsion of a testicular appendage in an adult male. PMID- 2200627 TI - The radioactive handkerchief sign. A contamination artifact in I-131 imaging for metastatic thyroid carcinoma. AB - False-positive findings suggestive of metastatic functioning thyroid carcinoma have been well documented in I-131 whole-body imaging. These artifacts are often associated with contamination from radioiodine-containing body secretions. Recently, a contaminated handkerchief on an iodine-131 whole-body scan was reported. In the following study, two additional cases involving the sequestration of I-131 contaminated handkerchiefs in patients' pockets are presented, and the literature regarding these false-positive findings is reviewed. Although rare, this "radioactive handkerchief sign" may cause serious misinterpretation of a focal radioiodine accumulation. PMID- 2200629 TI - Active bleeding after renal transplantation diagnosed by Tc-99m DTPA scanning. PMID- 2200630 TI - Intravascular contrast agents and renal failure. PMID- 2200631 TI - Imaging the painful shoulder. PMID- 2200632 TI - A double-blind comparison of iopromide and iopamidol in intravenous urography. AB - A randomised double-blind comparative study was performed to assess the imaging properties and side-effects of two non-ionic contrast media, iopromide and iopamidol, in intravenous urography in high risk patients. The results showed the two contrast media to be similar in their imaging efficacy and incidence of side effects. Using 50 or 100 ml of iopromide or iopamidol (370 mgI/ml), the quality of nephrograms was found to be dose dependent but the quality of pyelograms was not dose dependent. PMID- 2200633 TI - Intrasplenic metastases from carcinoma of the ovary. AB - Intrasplenic metastases are an uncommon manifestation of malignant disease. The relative paucity of splenic metastases is thought to be due to the properties of the spleen as an organ of immune surveillance. We report five cases of splenic metastases from carcinoma of the ovary demonstrated by CT scanning and ultrasound examination. In this series, splenic metastases were associated with bulk disease and more anaplastic tumours. Increased availability of magnetic resonance imaging may improve the recognition of splenic metastases. PMID- 2200634 TI - Quality assessment. An emerging component of hospital epidemiology. AB - Amid the national preoccupation for monitoring health care and health care providers, it is argued that quality assurance is basically an epidemiological pursuit. The study of the distribution and determinants of desirable health care- quality assurance--is best illustrated by the efforts of those who have worked to prevent and control the untoward outcomes associated with hospital-acquired infections. As such, infection control is the paradigm for quality assurance, and hospital epidemiology is the discipline best suited to deal with continual need for providing information for health care decisionmakers. PMID- 2200635 TI - Detection of group A streptococcal antigen from throat swabs with five diagnostic kits in general practice. AB - During a 5-month period, 248 general practitioners from 164 general practice offices obtained duplicate throat swabs from 2469 patients with acute pharyngotonsillitis. At the general practice office, one of the swabs was assayed for the presence of group A streptococcal antigen, using one of five commercially available diagnostic kits. (The participants did not receive instruction in the use of the kits). The other swab was cultured in our laboratory for the presence of group A streptococci. The diagnostic parameters for the five kits were as follows: Abbott TestPack Strep A--sensitivity, 79% (110/139) and specificity, 98% (490/501); Direct Strep A EIA (Roche)--sensitivity, 79% (104/132) and specificity, 63% (178/281); Respirastick--sensitivity, 55% (46/84) and specificity, 96% (298/309); Reveal Colour Strep A--sensitivity, 82% (114/139) and specificity, 83% (223/268); Tandem ICON Strep A--sensitivity, 78% (111/143) and specificity, 98% (362/368). The antigen detection test results were heavily influenced by the clinical prediction of a streptococcal or viral etiology. It is concluded that in the absence of a standard throat culture, the Abbott TestPack Strep A kit and the Tandem ICON Strep A kit both offer a more safe diagnostic alternative than clinical assessment. Depending on the current prevalence of group A streptococci, the additional use of a throat swab culture should be considered in case of negative antigen detection test results. PMID- 2200636 TI - Group G streptococcal meningitis and sepsis in a patient with AIDS. A method to biotype group G streptococcus. AB - Lancefield group G streptococcus is now recognized as a pathogen and has been reported to cause severe infections, including meningitis. We describe the first case of meningitis caused by this organism in a patient with acquired immunodeficiency syndrome (AIDS) and the direct transmission of the pathogen to a technologist accidentally exposed to the cerebrospinal fluid. To prove the identity of the two strains, we have tested them employing the Vitek system. We have also tested 13 other strains of group G streptococci obtained from different sources. Our results yielded 14 different biotypes with the 15 strains tested. The only identical ones were the two suspect strains from the index case and the technologist. We conclude that the biotyping system employed in our study appears to be a useful epidemiological tool for marking group G streptococci. PMID- 2200637 TI - Evaluation of three commercial tests for Lyme disease. AB - A commercial indirect immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), and a passive hemagglutination kit were evaluated and compared with our in-house IFA and ELISA methods. Both IFA methods gave identical results but were less sensitive than ELISA methods. Likewise, the ELISA methods were comparable. The hemagglutination method gave a statistically significant difference when compared with our ELISA method (p = 0.018 McNemar test). It is recommended that the passive hemagglutination method should not be used in its current state. PMID- 2200638 TI - Place of calcium antagonists in the treatment of hypertension. AB - The reduction of transmembraneous calcium influx into vascular smooth muscle cells by calcium antagonists leads to a reduction of tension development and vascular tone. Calcium antagonists reduce forearm vascular resistance dose dependently and this effect can be successfully utilized for the treatment of essential hypertension where they act by reducing increased peripheral vascular resistance thereby normalizing the main haemodynamic derangement of hypertensive patients. In contrast to other direct acting vasodilators the antihypertensive effect is not accompanied by sympathetic reflex activation or volume retention making it feasible to use calcium antagonists as monotherapy for hypertensive patients. In view of the well documented efficacy, tolerability and an excellent safety profile calcium antagonists have become drugs of choice for treatment of hypertension in many patients. Although all calcium antagonists have been shown to lower blood pressure they differ with respect to their vasodilating potency and their negative inotropic effects. The development of dihydropyridine calcium antagonists which are potent arterial vasodilators but have little if any negative inotropic effects at clinically used dosages further improves the safety profile of calcium antagonists, particularly when used in hypertensive patients with impaired left ventricular function. PMID- 2200639 TI - Muller cell GFAP expression exhibits gradient from focus of photoreceptor light damage. AB - High intensity (ca. 150 foot-candles), cumulative fluorescent light exposure regimes of 40 or 60 minutes to pigmented Long Evans rats were sufficient to elicit glial fibrillary acidic protein immunoreactivity (GFAP-IR) in Muller cells, when the animals are sacrificed 7 days post-exposure. Exposure to only 20 minutes of cumulative light or sacrifice immediately after exposure was not sufficient to initiate GFAP-IR in Muller cells. A gradient of GFAP-IR was observed extending from an approximately circular focus superior to the optic disc to the peripheral retina, whether or not there was morphological damage to the photoreceptors observable at the light microscopic level. Photoreceptor lesions produced by laser photocoagulation elicited the same gradient of GFAP-IR, and showed that GFAP-IR was not a reflection of a central to peripheral gradient of light received by the retina. Excessive light exposure initiated a signal which induced GFAP expression in Muller cells. This signal appeared to require a dark period and may be a diffusible factor that moves through extracellular pathways. PMID- 2200640 TI - Sympathetic ophthalmia, a genuine autoimmune disease. AB - Intraocular inflammation of exogenous origin, which may lead to the loss of visual function in both eyes, i.e. SO confronts ophthalmologists much less rarely than might be expected. Epidemiological studies comprising ergophthalmological aspects underscore this. Questions with regard to therapy should consider the fact that the T cell-mediated cytotoxic disease which causes the transition from the initially unilateral subthreshold exogenous uveitis into the bilateral progressive phase is by no means a rare disorder, especially in secondary surgical operations on predamaged eyes with fresh intraocular hemorrhages, vascular neoplasia and secondary glaucoma. This should be recalled again by practicing ophthalmologists, thus enabling the prevention of SO. If SO is a "forme fruste" of retinitis pigmentosa, as is very likely to be the case, further clarification requires clinicopathologic studies in close collaboration with immunologists. PMID- 2200641 TI - Experimental models of autoimmune diseases. AB - Several experimental models of autoimmune diseases have been studied which often mimic the human situation. Autoreactive T cells that emerge either spontaneously or after immunization have been identified in several situations. The main lesson from these models is that these autoreactive T cells are negatively controlled in the normal situation and that a defect either inherited or acquired in this regulatory circuit is responsible for autoimmunity. PMID- 2200642 TI - S-antigen in non ocular tissues. AB - S-antigen has been considered a specific protein of photoreactive cells by immunohistochemical criteria. It was observed in the retina and pineal gland of all examined vertebrates as well as in photoreceptors of invertebrates, but not currently in other organs. However, contrary to pineal cells of poikilotherms and birds which are true or modified photoreceptors, mammalian pinealocytes are not photosensitive. Recent experiments demonstrated that S-antigen-like proteins are present in low amount in many other cells in the body. These proteins are characterized by the same migration pattern (the same molecular weight) as retinal S-antigen in SDS-electrophoresis and by their immunoreactivity with a panel of monoclonal and polyclonal antibodies to S-antigen. These cells are not photosensitive, but are controlled by beta adrenergic, G-protein mediated adenylate cyclase system, a transduction system that shares many structural and functional homologies with visual transduction. S-antigen (arrestin) plays a regulatory role in phototransduction in rods by desensitizing rhodopsin. In the mammalian pineal and in other cells or tissues, S-antigen, or a family of structurally related proteins, could similarly be involved in the regulation of chemical signal transduction. Whether any systemic pathology is associated with uveoretinitis and pinealitis after S-antigen immunization deserves further investigations. PMID- 2200643 TI - Aqueous humor factors and their effect on the immune response in the anterior chamber. AB - The immune response to antigens within the anterior chamber is deviant (anterior chamber associated immune deviation - ACAID) in that delayed hypersensitivity is deficient, whereas other immune effector modalities are intact. Experimental evidence indicates that the eye itself is critical to the induction of ACAID. We have examined the antigen processing and presenting potential of cells within the anterior segment of the eye, and have analyzed the potential immunoregulatory properties of these cells, their secretory products, and the aqueous humor itself. Evidence indicates that bone marrow-derived cells within the stroma of the iris and ciliary body inhibit antigen-driven T lymphocyte activation, although they themselves lack the capacity to present antigens to T lymphocytes. The mechanism is in part through secretion of immunosuppressive cytokines. Since aqueous humor contains similar cytokines, it is inferred that these molecules are constitutively secreted. We have determined that a major inhibitory molecule within normal aqueous humor is transforming growth factor-beta (TGFB), which inhibits antigen processing and presentation, and suppresses both T lymphocyte activation and certain aspects of non-specific inflammation. These effects also turn out to be properties of normal aqueous humor. These findings support the hypothesis that local features of the eye modify intraocular antigens such that an ACAID-inducing signal is produced. Experimental evidence suggests that these same properties may play a major role in suppressing efferent immune responses in the eye. PMID- 2200644 TI - Regulation of the local immune response by retinal cells. AB - Experimental autoimmune uveoretinitis (EAU) induced by retinal antigens is a CD4+ (Th) lymphocyte mediated disease. Generation of autoreactive CD4+ cells requires the processing and presentation of autoantigen by antigen presenting cells (APC) in combination with MHC Class II antigen. Efficient presentation of antigen to T cells has also been shown to depend on accessory molecules of adhesion such as intercellular adhesion molecule-1 (ICAM-1) and leukocyte function-associated antigen-1 (LFA-1). Aberrant expression of Class II antigens by local tissue cells has been suggested as a possible mechanism in autoimmune processes. Several ocular cells express Class II antigens during inflammation, while other cells such as Muller cells inhibit antigen presentation in vitro. We have also shown that retinal pigment epithelial cells (constitutively) and endothelial cells (after induction) express ICAM-1 and that CD4+ lymphocyte adhesion to these cells is inhibited by antibodies to ICAM-1. Accessory molecules may therefore be important, not only in local presentation of antigen but in recruitment of circulating autoreactive cells to the eye since these cells represent the site of the blood-retinal barrier. Regulation of the local immune response in the eye therefore, may occur at several levels. PMID- 2200645 TI - Manipulation of the immune response by monoclonal antibodies in auto-immune pathology. AB - Murine monoclonal antibodies have proven to be invaluable tools in medical research and diagnosis. However, their use as therapeutic agents remains limited since these proteins can act as foreign antigens in the human host. An immune response subsequent to administration of monoclonal antibodies may result in unpredictable in vivo distribution and insufficient interaction with cellular or molecular targets of the immune system. Also, the patient may produce anti antibodies that can neutralize the effects of the therapeutically administered monoclonal antibodies. Treatment of auto-immune disease is an important potential therapeutic application of monoclonal antibodies, provided that these difficulties can be overcome. PMID- 2200646 TI - Cytokines and intraocular inflammation. AB - Although new endogenous mediators of inflammatory and immune responses are reported almost on a monthly basis, the cytokines IL-1, TNF, and IL-6 have emerged as the primary regulators of local inflammation in man. In this paper, uveitogenic and other properties of these particular cytokines are discussed and attention is payed to the possible involvement of a cytokine-network in the development of uveitis. PMID- 2200647 TI - HLA-B27 and acute anterior uveitis. AB - This article reviews the ophthalmological significance of the association between HLA-B27 and acute anterior uveitis (AAU). HLA-B27 determination should be performed in all cases of acute anterior uveitis (AAU), since B27+ AAU is a distinct kind of uveitis. All B27+ AAU patients have to be referred to a rheumatologist because half of these patients has ankylosing spondylitis or Reiter's syndrome. The structure and physiological role of HLA-class I molecules is now known. It is probable that the role of HLA-B27 in the pathogenesis of AAU will be revealed in the coming years. PMID- 2200648 TI - Humoral and cellular immune reactions against retinal antigens in clinical disease. AB - Autoimmune reactions against retinal antigens have been suggested to play an important role in clinical uveitis in man. As yet the evidence for this assertion is very weak. Sympathetic Ophthalmia is a disease entity which comes closest to acceptance as an autoimmune disease although the autoantigen involved has not been identified. Both cellular and humoral autoreactivity against retinal antigens have been found both in uveitis patients as well as in healthy controls. Very high levels of retinal antibodies were found in onchocerciasis patients but no relation was observed with the occurrence of chorioretinitis. Differences were observed when testing patient sera against human or bovine retinal antigens (S antigen or IRBP) emphasizing the need for using human tissue when investigating autoimmune responses. Circumstantial evidence in favor of an autoimmune etiology of uveitis include the morphology of the inflammatory infiltrate, effect of immuno-suppressive therapy and especially the establishment of experimental animal models. The experimental models of S-antigen or IRBP induced uveitis are primarily T cell mediated and also show pineal gland involvement. As yet no "established" human autoimmune disease has been described with a dominant role for T cells. Furthermore there is no evidence for pineal gland involvement in clinical uveitis. Analysis of the specificity of the T cell infiltrate or deposited immunoglobulins obtained from the diseased tissues may provide conclusive evidence for a possible autoimmune character of certain clinical uveitis entities. PMID- 2200650 TI - Recent developments in sexually transmitted diseases: is heterosexual transmission of HIV a major epidemiologic factor in the spread of AIDS? New York City's experience. PMID- 2200649 TI - Subungual keratoacanthoma: possible relationship to exposure to steel wool. PMID- 2200651 TI - Cutaneous metastases of colonic adenocarcinoma. AB - A case of metastatic colonic adenocarcinoma to the chin is presented. The literature on cutaneous metastases from colonic adenocarcinoma is reviewed. PMID- 2200652 TI - A trial of the Actiderm dermatological patch and topical corticosteroids in the treatment of psoriasis vulgaris. The Actiderm Multi-Center Study Group. AB - The use of the Actiderm dermatological patch in conjunction with topical corticosteroids was evaluated in a multi-centered, paired-comparison study of 189 patients with chronic psoriasis. In each patient, two lesions of comparable severity were selected for treatment. One plaque was treated with a twice-daily application of a steroid cream (triamcinolone acetonide 0.1 percent, betamethasone valerate 0.1 percent, or halcinonide 0.1 percent) while the second plaque was treated with a forty-eight hour application of the same steroid cream under Actiderm. At follow-up visits during the three-week treatment period and at four weeks post-treatment, the lesions were evaluated for the following parameters: erythema, induration, scale, and fissuring. For each of the three steroid preparations, the Actiderm and steroid therapy produced significant improvement in all parameters compared to the steroid therapy alone. This improvement was sustained through the post-treatment phase (p is less than 0.05 in all groups). No measurable differences in therapeutic efficacy were identified among the three steroid groups. Reports of adverse experiences in the Actiderm and steroid groups were infrequent. We conclude that the Actiderm and steroid combination is a safe and highly effective treatment for psoriasis. PMID- 2200653 TI - [Impression materials, alternatives for the practitioner and their consideration. Impression materials for complete dentures]. PMID- 2200654 TI - [Law of 14 Frimaire year III and its consequences for dentistry in the 19th century]. PMID- 2200655 TI - [Fabrication of custom angulator for automatic intraoral repositioning for retroalveolar radiography]. PMID- 2200656 TI - Influence of smear preparation and fixatives on the DNA ploidy and the morphonuclear features of the MXT mammary tumor and normal tissues in the mouse. AB - We compared cytomorphonuclear parameters--related to DNA histogram and chromatin distribution--on MXT mouse mammary tumor and murine normal cells from fresh squash smears or from deparaffinized tissue smears fixed in several fluids. We used the SAMBA 200 cell image processor with software allowing for the discrimination of parameters computed on Feulgen-stained nuclei. The spectrophotometric results--assessed by integrated optical density values- indicate that the nuclei from deparaffinized tissue fixed in Bouin's fluid are around 50% less stained than those fixed in formalin or ethanol-formalin-acetic acid (EFA). The fresh smears of nuclei fixed in formalin contain a less well defined and more homogeneous chromatin than after Bouin's or EFA fixation. This has led to the conclusion that morphonuclear parameter comparisons performed on tissues differently processed or from different origins present severe limitations. PMID- 2200657 TI - Two-color flow cytometric analysis of the expression of MAC and MHC class II antigens on macrophages during tumor growth. AB - Tumor-bearing host (TBH) macrophages (M phi) exhibit immune dysfunction that is concomitant with phenotypic changes. We examined M phi subpopulations by changes in the expression of surface antigens Mac-1, -2, -3, and Ia on normal and TBH peritoneal and splenic M phi. M phi were double-labeled and analyzed by flow cytometry to observe multiple expression of surface antigens. Tumor growth alters the multiple expression of these M phi markers. Peritoneal and splenic M phi had different Mac+ and Mac+Ia+ population percentages. In TBH, peritoneal M phi had decreased percentages of Mac-1+2+, Mac-1+3+, Mac-2+3+, and Mac+Ia+ M phi. This decrease correlated with functional changes in TBH M phi. In contrast, there was an increase in Mac-2-Ia- TBH peritoneal M phi. Previously undiscovered Mac-1+2-3- and Mac-1-2-3+ populations were found. In contrast to peritoneal M phi, there was an increase in the percentage of Mac-1+2+, Mac-1+3+, and Mac-2+3+ splenic TBH M phi but, like peritoneal M phi, there was a decrease in the percentage of Mac+Ia+ M phi. Also, TBH splenic M phi showed a smaller but more uniform antigen density than normal host splenic M phi. Tumor growth modulated phenotypic alterations in peritoneal and splenic M phi subpopulations. Combined with earlier functional studies of M phi subpopulations, these data suggested a relationship between changes in M phi phenotype and tumor-induced dysfunction of M phi-modulated immune activity. PMID- 2200658 TI - Bartter's syndrome associated with indirect hyperbilirubinemia: a possible clinical variety. AB - This report deals with three cases of Bartter's syndrome whose symptomatology was associated with indirect hyperbilirubinemia. The bilirubin disorder was suggestive of Gilbert's syndrome, with no pathological findings being detected as far as the liver function was concerned. Furthermore, the unconjugated fraction of bilirubin increased after fasting. The therapy with indomethacin exerted beneficial effects on both electrolytes and bilirubin disorders, and the patients recovered a good healthy state. These findings suggest the possibility that Bartter's syndrome may coexist in a variety associated with indirect hyperbilirubinemia. PMID- 2200659 TI - Angiotensin II generation in mesenteric arteries in rats: effects of nephrectomy, deoxycorticosterone and dexamethasone. AB - Angiotensin II (ANG II) generation in the mesenteric arteries was studied in four groups of rats: deoxycorticosterone (DOCA)/salt treated, glucocorticoid treated, nephrectomized and control rats. Basal plasma renin activity (PRA) was undetectable in the nephrectomized group and suppressed in the DOCA/salt treated rats, but was increased in the rats treated with glucocorticoid. The Basal plasma ANG II concentration changed comparably with PRA in all four groups of rats. In the control rats, ANG II was released from the mesenteric arteries at a rate of 43.0 +/- 12.0 pg/h, and it was not decreased by nephrectomy. In DOCA/salt rats and glucocorticoid rats, ANG II release significantly decreased to 12.8 +/- 7.1 and 6.9 +/- 1.5 pg/h, respectively. Captopril treatment significantly reduced ANG II release from the mesenteric arteries in both controls and nephrectomized rats, but did not influence ANG II output in DOCA/salt rats or in glucocorticoid treated rats. In nephrectomized rats, captopril lowered blood pressure in association with a significant reduction in the mesenteric ANG II formation. These results indicate that the renal and vascular renin-angiotensin system (RAS) may be independently regulated, and in nephrectomized animals the vascular RAS contributes in part to the maintenance of blood pressure. The present results also suggest that volume expansion per se and/or pharmacological intervention by DOCA and glucocorticoid could modulate vascular ANG II generation. PMID- 2200660 TI - Overview of inhalation toxicology. AB - The development of inhalation toxicology as a distinct discipline can be traced back well over one hundred years. The technology has advanced in terms of materials and designs used to construct inhalation chambers and the equipment used to generate controlled test atmospheres of a wide variety of gases, vapors, dusts, and droplets. Consideration of metered dose inhalers, a relatively recent concern, has led to the design of new equipment for administering this unique dosage form. The parameters used to evaluate inhalation toxicity are similar to those used for any other route of administration. In addition, there are some unique procedures for early screening of pulmonary toxicity, especially within a series of related chemicals. PMID- 2200661 TI - Biotransformation enzymes in the rodent nasal mucosa: the value of a histochemical approach. AB - An increasing number of chemicals have been identified as being toxic to the nasal mucosa of rats. While many chemicals exert their effects only after inhalation exposure, others are toxic following systemic administration, suggesting that factors other than direct deposition on the nasal mucosa may be important in mechanisms of nasal toxicity. The mucosal lining of the nasal cavity consists of a heterogeneous population of ciliated and nonciliated cells, secretory cells, sensory cells, and glandular and other cell types. For chemicals that are metabolized in the nasal mucosa, the balance between metabolic activation and detoxication within a cell type may be a key factor in determining whether that cell type will be a target for toxicity. Recent research in the area of xenobiotic metabolism in nasal mucosa has demonstrated the presence of many enzymes previously described in other tissues. In particular, carboxylesterase, aldehyde dehydrogenase, cytochromes P-450, epoxide hydrolase, and glutathione S transferases have been localized by histochemical techniques. The distribution of these enzymes appears to be cell-type-specific and the presence of the enzyme may predispose particular cell types to enhanced susceptibility or resistance to chemical-induced injury. This paper reviews the distribution of these enzymes within the nasal mucosa in the context of their contribution to xenobiotic metabolism. The localization of the enzymes by histochemical techniques has provided important information on the potential mechanism of action of esters, aldehydes, and cytochrome P-450 substrates known to injure the nasal mucosa. PMID- 2200662 TI - Normal histology of the nasal cavity and application of special techniques. AB - There are three major epithelial types in the nasal mucosa, in addition to numerous accessory structures, some of which are species specific. Without careful and consistent processing of the nose tissue, histopathologic assessment of lesions in the nasal cavity may be compromised. While formalin fixation may be used for routine review of the nasal cavity, Bouin's fixation provides better histologic detail and fewer artifacts. Decalcification is not recommended for nasal tissues to be examined by transmission electron microscopy because of the detrimental effect of decalcifying solutions on sensory cells. Three levels of the nasal cavity may be used for routine histologic review of the nasal cavity, but four or five levels may be more appropriate for certain studies. PMID- 2200663 TI - Airflow, gas deposition, and lesion distribution in the nasal passages. AB - The nasal passages of laboratory animals and man are complex, and lesions induced in the delicate nasal lining by inhaled air pollutants vary considerably in location and nature. The distribution of nasal lesions is generally a consequence of regional deposition of the inhaled material, local tissue susceptibility, or a combination of these factors. Nasal uptake and regional deposition are are influenced by numerous factors including the physical and chemical properties of the inhaled material, such as water solubility and reactivity; airborne concentration and length of exposure; the presence of other air contaminants such as particulate matter; nasal metabolism, and blood and mucus flow. For certain highly water-soluble or reactive gases, nasal airflow patterns play a major role in determining lesion distribution. Studies of nasal airflow in rats and monkeys, using casting and molding techniques combined with a water-dye model, indicate that nasal airflow patterns are responsible for characteristic differences in the distribution of nasal lesions induced by formaldehyde in these species. Local tissue susceptibility is also a complex issue that may be a consequence of many factors, including physiologic and metabolic characteristics of the diverse cell populations that comprise each of the major epithelial types lining the airways. Identification of the principal factors that influence the distribution and nature of nasal lesions is important when attempting the difficult process of determining potential human risks using data derived from laboratory animals. Toxicologic pathologists can contribute to this process by carefully identifying the site and nature of nasal lesions induced by inhaled materials. PMID- 2200664 TI - Infectious diseases of the upper respiratory tract: implications for toxicology studies. AB - The consequences of adventitious infectious agents upon the interpretation of toxicology studies performed in rats and mice are incompletely understood. Several prevalent murine pathogens cause alterations of the respiratory system that can confuse the assessment of chemically induced airway injury. In some instances the pathogenesis of infection with these agents has been relatively well studied in the lower respiratory tract. However, there are few well controlled studies that have examined the upper respiratory region, which result in interpretive problems for toxicologic pathologists. The conduct and interpretation of both short-term and chronic rodent bioassays can be compromised by both the clinical and subclinical manifestations of infectious diseases. This paper reviews several important infectious diseases of the upper airway of rats and mice and discusses the potential influence of these conditions on the results of toxicology studies. PMID- 2200665 TI - Nonneoplastic nasal lesions in rats and mice. AB - Rodents are commonly used for inhalation toxicology studies, but until recently the nasal passages have often been overlooked or only superficially examined. The rodent nose is a complex organ in which toxicant-induced lesions may vary, depending on the test compound. A working knowledge of rodent nasal anatomy and histology is essential for the proper evaluation of these responses. Lack of a systematic approach for examining rodent nasal tissue has led to a paucity of information regarding nonneoplastic lesions in the rodent nose. Therefore, slides from the National Toxicology Program (NTP) and the Chemical Industry Institute of Toxicology (CIIT) were examined, and the literature was reviewed to assemble the spectrum of nonneoplastic rodent nasal pathology. Presented are lesions associated with the various types of epithelia lining the rodent nasal cavity plus lesions involving accessory nasal structures. Even though there are anatomic and physiologic differences between the rodent and human nose, both rats and mice provide valuable animal models for the study of nasal epithelial toxicity, following administration of chemical compounds. PMID- 2200666 TI - The importance of epithelial uptake systems in lung toxicity. AB - The discovery that the herbicide paraquat was selectively accumulated by the lung, both in vivo and in vitro, in comparison with other tissues, provided an explanation for its selective toxicity to the lung. This uptake process is energy dependent and obeys saturation kinetics. A characterization of the process led to the identification of endogenous chemicals that are the natural substrates for the system. Among these are a series of diamines and polyamines, as well as the diaminodisulfide cystamine. It appears that paraquat, because of specific structural similarities to these endogenous polyamines, is mistakenly accumulated by the lung. This uptake process is specifically located in the alveolar Type II cell, the Clara cell, and probably the alveolar Type I cell. With the development of knowledge of the structural requirements of chemicals to be accumulated by this system, it is possible to predict which chemicals will be accumulated by the lung or design molecules that are targeted to the alveolar epithelial and Clara cells. In the wider perspective, this polyamine uptake system has been found on a number of cancerous cells or tissues. With the knowledge of the uptake system in the lung, it should be possible to design drugs that will be specifically concentrated in cells that possess this system. PMID- 2200667 TI - Nonneoplastic changes in the olfactory epithelium--experimental studies. AB - Interest in the olfactory mucosa has increased in recent years, since it has been shown to possess a considerable amount of cytochrome P-450-dependent monooxygenase activity and a wide variety of chemicals have been identified as olfactory toxins. Many chemicals induce lesions of a general nature in the olfactory mucosa, i.e., inflammation, degeneration, regeneration, and proliferation, whereas others cause more specific effects. Changes in the olfactory mucosa with reference to chemicals that initiate them are reviewed in this paper. Studies with 3-trifluoromethyl pyridine (3FMP) illustrate some of these general changes and show the importance of examining the olfactory mucosa at early time periods. The earliest damage seen by light microscopy was 6 hr after a single inhalation exposure to 3FMP, and by day 3, early regenerative changes were observed. Changes were seen by electron microscopy 30 min after an oral dose, and the primary site of toxicity appeared to be the Bowman's glands. Although atrophy of nerve bundles in the lamina propria would be the expected consequence of severe necrosis of the sensory cells, this is not always the case. Exposure to irritants such as acetaldehyde, formaldehyde, and dimethylamine results in nerve bundle atrophy, but with chemicals such as 3FMP, 3-methylindole, and 3-methylfuran--which are activated by mixed-function oxidases--the nerve bundles remain intact. Future work, including metabolism studies, will provide information on the mode of action of these chemicals. PMID- 2200669 TI - Isolation of Clara cells from the mouse lung. AB - A method is described for isolating Clara cells from the mouse lung that does not require the technique of elutriation. Mouse lungs totally perfused of blood are instilled with crystalline trypsin (0.25%) and incubated for the optimum time of 15 min. The lung tissue is chopped, mechanically agitated, and sequentially filtered to obtain a primary digest of 3 to 5 x 10(6) cells. Clara cells, identified routinely by histochemical localization of NADPH diaphorase, using the stain nitrotetrazolium blue (NBT), accounts for between 20 to 40% of the cells in the primary digest. Layering the cells of the primary digest on a discontinuous Percoll gradient followed by centrifugation gives rise to a major band of cells, 52% that are Clara cells (0.77 +/- 0.28 x 10(6)/mouse). A second method was devised to purify the Clara cells by simply centrifuging (32g, 6 min, 10 degrees C) the primary digest and discarding the supernatant that contained only a few NBT positive cells. When this process was repeated three times, the final pellet contained 68% Clara cells realizing 0.55 +/- 0.16 x 10(6) cells/mouse. The cells have typical Clara cell morphology as confirmed by electron microscopy and have a high level of P-450 enzymes (7-ethoxycoumarin deethylase and coumarin hydroxylase). Furthermore, the primary digests and the purified isolates contain less than 1% alveolar Type II cells, although such cells, identified by the histochemical localization of alkaline phosphatase, can be obtained by a second, more extensive digestion procedure. The simple procedure described for the isolation of mouse Clara cells could be further advanced if methods could be devised to prevent the loss of NADPH diaphorase activity during enzymatic digestion and cell centrifugation. PMID- 2200670 TI - Translation and regulation of translation in the yeast Saccharomyces cerevisiae. AB - In recent years the yeast Saccharomyces cerevisiae has become a model system for studies of eukaryotic translation and translation regulation. Analysis of mRNA structure, translation initiation factor sequences and the translation initiation pathway indicate, that translation in S. cerevisiae is very similar to translation in higher eukaryotes. The availability of powerful genetic techniques lead to the dissection in yeast of individual steps in the translation pathway, the detection of biochemical interactions between components involved in translation and the unravelling of complex regulation phenomena. PMID- 2200668 TI - Pulmonary metabolism of foreign compounds: its role in metabolic activation. AB - The lung has the potential of metabolizing many foreign chemicals to a vast array of metabolites with different pharmacological and toxicological properties. Because many chemicals require metabolic activation in order to exert their toxicity, the cellular distribution of the drug-metabolizing enzymes in a heterogeneous tissue, such as the lung, and the balance of metabolic activation and deactivation pathways in any particular cell are key factors in determining the cellular specificity of many pulmonary toxins. Environmental factors such as air pollution, cigarette smoking, and diet markedly affect the pulmonary metabolism of some chemicals and, thereby, possibly affect their toxicity. PMID- 2200671 TI - Isolation of two high-molecular-mass proteinases from human erythrocytes. AB - Two forms of a neutral--alkaline high-molecular-mass proteinase (termed A1 and A2) have been purified from human erythrocytes by a procedure including a DEAE cellulose batchwise treatment of erythrocyte cytosol, gel filtration and DEAE cellulose chromatography. Both enzymes show distinctive properties of multicatalytic proteinases. They have an apparent molecular mass of 700 kDa and are composed by eight major subunits (23-32 kDa). Both enzymes show a proteinase activity towards casein and hydrolyze synthetic peptides with tyrosine, arginine or lysine at the P1 position. Among the synthetic peptides tested, the tetrapeptide succinyl-leucyl-leucyl-valyl-tyrosyl-7-amido-4-methylcoumarin and tripeptides with arginine in the P1 position (benzyloxycarbonyl-valyl-leucyl arginyl-4-methoxy-2-naphthylamide and benzyloxycarbonyl-alanyl-arginyl-arginyl-4 methoxy-2-naphthylamide) are the most effective substrates. The proteinases are devoid of amino and diaminopeptidase activity. Both enzymes are completely inhibited by hemin, chymostatin and thiol-group reagents. However, the enzymes can be distinguished by the isoelectric point, the different effect of nucleotides, glutathione disulphide, sodium dodecyl sulfate and cations on the catalytic activity. PMID- 2200672 TI - Nucleotide sequence, organisation and structural analysis of the products of genes in the nirB-cysG region of the Escherichia coli K-12 chromosome. AB - The DNA sequence and derived amino-acid sequence of a 5618-base region in the 74 min area of the Escherichia coli chromosome has been determined in order to locate the structural gene, nirB, for the NADH-dependent nitrite reductase and a gene, cysG, required for the synthesis of the sirohaem prosthetic group. Three additional open reading frames, nirD, nirE and nirC, were found between nirB and cysG. Potential binding sites on the NirB protein for NADH and FAD, as well as conserved central core and interface domains, were deduced by comparing the derived amino-acid sequence with those of database proteins. A directly repeated sequence, which includes the motif -Cys-Xaa-Xaa-Cys-, is suggested as the binding site for either one [4Fe-4S] or two [2Fe-2S] clusters. The nirD gene potentially encodes a soluble, cytoplasmic protein of unknown function. No significant similarities were found between the derived amino-acid sequence of NirD and either NirB or any other protein in the database. If the nirE open reading frame is translated, it would encode a 33-amino-acid peptide of unknown function which includes 8 phenylalanyl residues. The product of the nirC gene is a highly hydrophobic protein with regions of amino-acid sequence similar to cytochrome oxidase polypeptide 1. PMID- 2200673 TI - Transcriptional control of the cysG gene of Escherichia coli K-12 during aerobic and anaerobic growth. AB - The 74-min region of the Escherichia coli chromosome includes five open reading frames of known sequence. The first and last of these genes, nirB and cysG, are transcribed in the same direction and both are essential for NADH-dependent nitrite reductase activity. The functions of the other genes, nirD, nirE and nirC, which are located between nirB and cysG, are unknown. The nirB gene is transcribed from a promoter which is anaerobically induced, expression being dependent on the transcription activator protein, Fnr. Here we show that the nirD, nirE, nirC and cysG genes are also expressed from the nirB promoter. After subcloning cysG, a second promoter was located less than 100 bases upstream of cysG. Two groups of transcription start points separated by 40 bases were detected in this region by S1 mapping. Rates of transcription from the isolated cysG promoter were the same during aerobic growth and anaerobic growth in the presence or absence of nitrite. However, when the nirB gene and its promoter were cloned back upstream from the cysG promoter, the rate of transcription was higher during anaerobic growth than during aerobic growth and was further induced by nitrite. These increases were totally dependent on a functional fnr gene and were shown by S1 mapping experiments to be due to transcriptional read-through from the Fnr-dependent nirB promoter. No promoter activity was associated with DNA fragments between the BamHI site located within the N-terminal coding region of the nirB gene and the cysG promoter located at the C-terminus of nirC. PMID- 2200674 TI - Cloning and sequence analysis of the genes encoding the alpha and beta subunits of the E1 component of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus. AB - A 4175-bp EcoRI fragment of DNA that encodes the alpha and beta chains of the pyruvate dehydrogenase (lipoamide) component (E1) of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus has been cloned in Escherichia coli. Its nucleotide sequence was determined. Open reading frames (pdhA, pdhB) corresponding to the E1 alpha subunit (368 amino acids, Mr 41,312, without the initiating methionine residue) and E1 beta subunit (324 amino acids, Mr 35,306, without the initiating methionine residue) were identified and confirmed with the aid of amino acid sequences determined directly from the purified polypeptide chains. The E1 beta gene begins just 3 bp downstream from the E1 alpha stop codon. It is followed, after a longer gap of 73 bp, by the start of another but incomplete open reading frame that, on the basis of its known amino acid sequence, encodes the dihydrolipoyl acetyltransferase (E2) component of the complex. All three genes are preceded by potential ribosome-binding sites and the gene cluster is located immediately downstream from a region of DNA showing numerous possible promoter sequences. The E1 alpha and E1 beta subunits of the B. stearothermophilus pyruvate dehydrogenase complex exhibit substantial sequence similarity with the E1 alpha and E1 beta subunits of pyruvate and branched-chain 2-oxo-acid dehydrogenase complexes from mammalian mitochondria and Pseudomonas putida. In particular, the E1 alpha chain contains the highly conserved sequence motif that has been found in all enzymes utilizing thiamin diphosphate as cofactor. PMID- 2200676 TI - Structural requirements for signal transduction of the insulin receptor. AB - Structural requirements for signal processing by human placental insulin receptors have been examined. Insulin binding has been found to change the physico-chemical properties of (alpha beta)2 receptors solubilized with Triton X 100, indicating a marked alteration of the form, i.e. size and shape, of the molecular complex. (a) The Stokes radius decreases from about 9.5 nm to 7.9 nm, as determined by PAGE with Triton X-100 in the buffer (Triton X-100/PAGE), and from 9.1 nm to 8.7 nm, as assessed by gel filtration. (b) The sedimentation coefficient s20,w rises from 10.1 S to 11.4 S. Upon dissociation of the receptor hormone complex, the alterations are reversed. After autophosphorylation of hormone-bound (alpha beta)2-insulin receptors, phosphate incorporation was found for 7.9-nm receptor forms when receptor-insulin complexes were crosslinked with disuccinimide suberate prior to Triton X-100/PAGE. However, phosphate incorporation was demonstrated for the 9.5-nm receptor forms when receptor insulin complexes were not prevented from dissociation. This strongly indicates that the (alpha beta)2 receptor is autophosphorylated after assuming its 7.9-nm form upon insulin binding. Moreover, the insulin-dependent structural alterations are not affected by autophosphorylation. In contrast to (alpha beta)2 receptors, the diffusion and the sedimentation behaviour of alpha beta receptors, which carry a dormant tyrosine kinase even in the hormone-laden state, has been found to be insensitive to insulin binding. Different molecular properties of alpha beta and (alpha beta)2 receptors have also been detected by hormone binding studies. Insulin binding to (alpha beta)2 and alpha beta receptors differs markedly with respect to pH, ionic strength, and temperature. This might indicate that the structure of the hormone binding domain of alpha beta receptor changes on association into the (alpha beta)2 species. Alternatively, distinct hormone induced conformational alterations at the molecular level of alpha beta and (alpha beta)2 receptor species may lead to the different binding properties. Our data demonstrate that the (alpha beta)2-insulin receptor undergoes extended conformational alterations upon insulin binding. This capacity for structural changes coincides with the hormone-inducable enhancement of tyrosine autophosphorylation of the 7.9-nm insulin-bound receptor form. In contrast, alpha beta receptors appear to be locked in an inactive nonconvertable state. Thus, interaction between two alpha beta receptor units is required to allow extended conformational alterations, which are assumed to be the triggering event for augmented auto-phosphorylation. PMID- 2200675 TI - Expression of cytochrome P-450 enzymes in cultured human hepatocytes. AB - Hepatocytes from adult and newborn humans were put into primary culture and exposed to phenobarbital, 3-methylcholanthrene, or rifampicin, three well-known inducers of cytochrome P-450 in animals. The expression of four cytochrome P-450 enzymes (or groups of enzymes, namely P-450 IIIA, P-450 IIC8/9/10, P-450 IIE1, and P-450 IA2) was investigated. These enzymes were found to remain expressed during the period of culture studied. Treatment with the inducers for three days resulted in different responses, depending upon the inducer and the enzyme. Phenobarbital and rifampicin increased P-450 IIC8/9/10 mRNA transcripts and the corresponding protein, while 3-methylcholanthrene was ineffective. Both P-450 IIIA mRNA and protein were strongly induced by rifampicin. All of the hepatocytes were found to synthesize P-450 IIIA in response to rifampicin, as shown by immunoperoxidase staining. P-450 IIIA expression was not affected by phenobarbital and was decreased by 3-methylcholanthrene. P-450s IA2 and IIE1 decreased to 25-50% of the initial level during these cultures. P-450 IA2 and ethoxyresorufin O-deethylase activity (which is a monooxygenase activity related to P-450 IA family) were increased only by 3-methylcholanthrene and did not respond to the other inducers. P-450 IIE1 was not induced by any of these compounds. P-450 IIC8/9/10 and P-450 IIIA mRNA levels were also measured in human hepatocytes from one newborn. P-450 IIC8/9/10 was barely expressed in freshly isolated cells but increased dramatically with time in culture. P-450 IIIA transcripts were abundant in both freshly isolated and cultured cells derived from a newborn. These results clearly demonstrate that human hepatocytes continue to express cytochrome P-450 enzymes and respond to inducers in culture. This model system provides a useful approach for investigating the effects of drugs on maturation and expression of drug-metabolizing enzymes in human liver. PMID- 2200677 TI - Cell adhesion, spreading and neurite stimulation by laminin fragment E8 depends on maintenance of secondary and tertiary structure in its rod and globular domain. AB - The cell adhesion, spreading and neurite-promoting properties of mouse tumor laminin fragment E8, which contains major site(s) responsible for laminin-cell interactions, were probed by proteolytic degradation, denaturation, synthetic peptides and antibody inhibition. Removal of more than half of the N-terminal portion contributing to the rod-like domain did not effect cell attachment or spreading although neurite-promoting activity was reduced. More extensive degradation of the rod or of the globular domains of E8, or separation of the globule from the rod, also resulted in loss of cell spreading activity although weak attachment was found to an A chain subfragment comprising the globular domain and a short piece of the rod. Exposure of E8 to increasing concentrations of dissociating agents produce an apparently reversible denaturation but an irreversible loss of both attachment and neurite-promoting activities, as did reduction and alkylation of disulfide bonds in the globular domain. Although cell adhesion and spreading were blocked by antibodies to an alpha 6 integrin subunit, neurite outgrowth was unaffected, indicating two distinct receptors for these two activities. Furthermore, a synthetic peptide, the sequence of which is found in the vicinity of adhesion and neurite-promoting sites and previously implicated in neurite growth and cell attachment activities, was found to be inactive. These results indicate that the major cell attachment and neurite-promoting sites of laminin are distinct although both require the native conformation of parts of the rod and the terminal globular domain of the long arm of laminin. PMID- 2200678 TI - Immunoscintigraphy of thrombosis. PMID- 2200679 TI - Investigation by scintigraphic methods of neutrophil kinetics under normal and septic shock conditions in the experimental baboon model. AB - The purpose of this study was the correlation of neutrophil kinetics with the pathogenic course of septic shock in the baboon model. Radioactively labelled neutrophils were traced in vivo in normal baboons (n = 6) and in Escherichia coli infected baboons, which were reinjected with labelled autologous neutrophils either 2 h after the onset of the E. coli infusion (procedure A) (n = 3) or simultaneously with the infusion (procedure B) (n = 3). Cell isolation was done according to a method developed in this laboratory. The cells were labelled with tropolonate In 111, resuspended in 1-2 ml plasma and reinjected. One-minute images were taken every 5th min and then hourly for 4 h with a gamma camera and analysed with a data processor. Time-activity curves were obtained for neutrophil washout from the lungs and neutrophil accumulation in the liver and spleen. These curves were compared for normal baboons and for those treated according to procedures A and B. A significant retention of neutrophils in the lungs of baboons with E. coli-induced septic shock was noted as well as an abnormally slow rate of accumulation in the liver and spleen. It also seems that any lung injury which could be attributed to changes in neutrophil behaviour should be traced back to events during the early exposure of neutrophils to bacterial infection. PMID- 2200680 TI - Current role of gallium scanning in the management of lymphoma. AB - Gallium 67 scanning in the malignant lymphomas has been done, with variable success, for over 20 years. After initial enthusiasm, the technique fell into disrepute and it was not until the early 1980s that it enjoyed a revival. There have been many major contributions to the literature, both favourable and unfavourable. The reasons for the latter include: poor instrumentation (only single-pulse height analysis), low gallium 67 doses, impatient and careless scanning techniques, timing of the study after treatment (chemotherapy, radiation) and insensitive methods of confirmation of the presence or absence of disease ("truth"). Anatomical diagnostic techniques (computed tomography, plain X radiography, magnetic resonance imaging and others) are incapable of distinguishing viable tumour in normal-size lymph nodes or necrotic/fibrotic residual masses. With improvements in instrumentation (triple-pulse height analysis, gamma camera resolution and tomographic techniques) gallium 67 can detect active tumour in residual masses and in normal-size nodes. This is due to gallium 67's unique ability to localize in viable tumour cells. It has greater than 90% sensitivity, specificity, accuracy and positive predictive value in patients with lymphoma. Its major contributions are in: staging (changing management of mediastinal disease, obviating the need for a laparotomy and clearly identifying stage IV disease); detecting relapse or residual, progressive disease (it establishes true complete remission and is often the first and only evidence of relapse before clinical evidence); predicting response to therapy (failure to convert to a negative scan post-treatment signals a poor prognosis and alternative therapy is required); and predicting outcome--prognosis (it is the only diagnostic modality to predict outcome accurately). PMID- 2200681 TI - Stereoselectivity in clinical pharmacokinetics and drug development. PMID- 2200682 TI - NMR studies of drug metabolism and disposition. AB - The ways in which NMR is being used in vivo to study drug metabolism and disposition are reviewed. We also assess the role of this technique as a non invasive method for monitoring the fate of drugs in human and animals, and for providing information about pharmacology and toxicity. PMID- 2200683 TI - Prodrugs for the improvement of drug absorption via different routes of administration. AB - The authors critically review recent knowledge on the use of prodrugs to improve drug absorption. Main emphasis is placed on the parenteral, oral, transdermal and ocular routes. Mechanisms for drug absorption enhancement and bioavailability assessment are discussed. Some other applications of prodrugs are also examined. Finally, some comments are made regarding the present situation and future trends in prodrug design and their implications in biopharmaceutics and pharmacokinetics. PMID- 2200684 TI - Improvement of drug absorption through enhancers. AB - The application of enhancers for improvement of drug absorption via the nasal, transdermal and rectal route are outlined. The importance of the relation between the time course of the enhancing effect and the desired plasma - concentration - time profile of the drug is stressed as well as the need to pay more attention to the safety aspects of absorption enhancers. PMID- 2200685 TI - Cell culture techniques for the study of drug transport. AB - The growth of differentiated cell monolayers on microporous filters is providing powerful new techniques for investigating the transport of drug and delivery systems across defined cellular barriers, and for discriminating between different routes and mechanisms. The growth, characterization and potential use of these systems is illustrated by studies on the human Caco-2 cell system which provides an in vitro model of the intestinal epithelial barrier. This system, still in the early stages of characterization and development, displays a number of carrier-mediated and vesicular transport systems found in the intestine in vivo, and is thus providing a useful system for studying the intestinal transport of drugs including peptides and proteins. PMID- 2200686 TI - Human hepatocytes as a key in vitro model to improve preclinical drug development. AB - Over past decades, numerous in vitro and/or ex vivo models have been developed to investigate drug metabolism. In the order of complexity we found the isolated perfused liver, hepatocytes in co-culture with epithelial cells, hepatocytes in suspension and in primary culture and subcellular hepatic microsomal fractions. Because they can be easily prepared from both animals (pharmacological and toxicological species) and humans (whole livers as well as biopsies obtained during surgery) hepatocytes in primary culture provide the most powerful model to better elucidate drug behavior at an early stage of preclinical development such as: the characterization of main biotransformation reactions, the identification of phase I and phase II isozymes involved in such reactions, the evaluation of inter-species differences allowing the selection of a second toxicological animal species more closely related to man on the basis of metabolic profiles, the detection of the inducing and/or inhibitory effects of a drug on metabolic enzymes, the prediction of drug interactions, the estimation of inter-individual variability in biotransformation reactions. The use of hepatocytes, and in particular those obtained from humans, at an early stage of drug development allows the obtention of more predictive preclinical data and a better knowledge of drug behavior in humans before the first administration of the drug in healthy volunteers. PMID- 2200687 TI - Pharmacokinetic characterization of controlled-release formulations. AB - The development of controlled-release formulations should be based on a clinico pharmacological rationale such as increased compliance, reduced side effects and improved efficacy. The pharmacokinetic profile of a controlled-release formulation and its dose regimen should be compared under steady-state conditions with that of an immediate-release formulation or that of another controlled release formulation. Apart from conventional characteristics such as AUC, tmax and Cmax, alternative characteristics are suggested such as residual concentration at the end of the dose interval, peak-through fluctuation in steady state, plateau time, statistical moments, in vivo input functions and intravenous infusion schemes which mimic the concentration/time profile after oral administration of the controlled-release formulation. The pharmacokinetic steady state profile should be reproduced with and without food, from day to day, and at various dose levels. The in vitro specification should be based on in vivo requirements for "within-product bioequivalence". PMID- 2200688 TI - Transport of peptide and protein drugs across biological membranes. AB - The transport characteristics of peptide and proteins drugs across various epithelial membrane barriers are outlines. These include transport through the intestinal, buccal, nasal and pulmonary absorptive mucosae, as well as transdermal penetration. Because peptides and proteins are hydrophilic and high molecular weight compounds, they commonly show minor permeability across the mentioned biological membranes. In order to improve their transport properties and thereby their systemic bioavailability, several strategies can be undertaken, such as the synthesis of stabilized and lipophilic analogues, the application of absorption enhancers and protease inhibitors, and the design of suitable dosage forms (e.g., liposomes, biodegradable nanocapsules, bioadhesive microspheres). PMID- 2200689 TI - Drug delivery systems and routes of administration of peptide and protein drugs. AB - The unique requirements of peptides and proteins in designing delivery systems, and the unprecedented recent growth in the field, has driven a great deal of research into novel means of drug delivery. The search for approaches that provide formulations that are stable, bioavailable, readily manufacturable, and acceptable to the patient, has led to major advances in development of nasal and controlled release technology. The field of parenteral solution technology has also seen some new demands made of it, and what was formerly a conventional area of formulation technology has made scientific advances to meet the needs of these compounds. At the same time, strides are being made in fundamental research in areas including oral delivery, transdermal delivery, and pulsatile and 'on demand' delivery of peptides and proteins. PMID- 2200690 TI - Glucose tolerance and insulin secretion in experimental peritonitis in the rat. AB - The changes in the regulation of insulin secretion that accompany sepsis are yet to be fully established. We therefore examined insulin secretion both in vivo and in vitro in 2 different models of peritonitis/sepsis in the rat. Sepsis was induced by intraperitoneal injection of Escherichia coli either alone or together with bile. Following sepsis induction, an initial hyperglycemia developed. This hyperglycemia was transient and had vanished after 3 h (coli group) or 9 h (bile group). However, after 24 h, a second phase of hyperglycemia developed in both groups. The glucose elimination rate after intravenous glucose injection (0.5 g/kg) at 4 and 10 h after peritonitis/sepsis induction was retarded and the hyperglycemia that occurred during intravenous glucose infusion (10 mg/min for 30 min) was exaggerated. This is consistent with a reduced glucose uptake. Simultaneously, the plasma insulin responses to glucose were markedly exaggerated. This could be due to a true potentiated insulin secretion or simply to an adaptation to the hyperglycemia. However, also during intravenous arginine infusion (7 mg/min) at 4 h after peritonitis/sepsis induction, the plasma insulin responses were markedly exaggerated. Since only a slight change in plasma glucose occurred during this challenge, the results suggest that sepsis is accompanied by a true hypersecretion of insulin. To verify whether this is directly or indirectly mediated, pancreatic islets were isolated from peritonitis/sepsis animals at 4 h after disease induction and incubated for 45 min in a KRB medium supplemented with different concentrations of glucose. The subsequent insulin secretion was the same in islets from the septic animals as in controls. Hence, our results show that experimental peritonitis/sepsis in the rat is accompanied by (1) glucose intolerance and (2) a true hypersecretion of insulin which is indirectly mediated. PMID- 2200691 TI - Are different hemodynamic patterns of antihypertensive drugs clinically important? AB - Since vascular resistance is elevated in hypertension, it is suggested that vasodilators lower the blood pressure by a physiologic mechanism and therefore must be more useful than cardiac output-lowering drugs. This is not entirely correct. Drugs that lower cardiac output are also relative vasodilators, but the vasodilation occurs at a lower level of cardiac output. It is also not necessarily true that all vasodilators are good antihypertensive agents. The clinical profile of a vasodilator depends on its effect on the venous return, cardiac output, regional blood flow, renin-angiotensin system, and sympathetic reflexes. From the viewpoint of hemodynamics, an ideal antihypertensive drug is a vasodilator that does not excessively increase cardiac output, causes no fluid retention, does not induce a great deal of venodilation, and does not elicit substantial neurohumoral counterregulation. Angiotensin-converting-enzyme inhibitors, some calcium antagonists, and some combined alpha/beta-blocking agents come close to satisfying the hemodynamic definition of an ideal antihypertensive drug. PMID- 2200692 TI - Do different hemodynamic effects of antihypertensive drugs translate into different safety profiles? AB - Various antihypertensive drugs reduce blood pressure by different mechanisms. In some instances, adverse reactions occur because of specific hemodynamic effects. Examples include syncope with alpha-blockade or vasodilator therapy; fatigue or exercise intolerance with the reduction in cardiac output following the use of beta-adrenergic inhibitors; edema, headaches, or dizziness with the use of vasodilators such as calcium entry blockers; renal failure in patients with renal artery stenosis or renal insufficiency following the use of ACE inhibitors; and marked hyponatremia with volume depletion following the use of diuretics, especially in elderly patients. In the majority of patients, however, blood pressure lowering can be achieved without significant adverse effects. Combining small doses of different agents with different hemodynamic actions often results in good blood pressure control and minimal reactions. Examples of these include diuretics and beta-adrenergic inhibitors, diuretics and ACE inhibitors, and beta blockers and vasodilators. PMID- 2200693 TI - Pharmacology of antihypertensive agents with multiple actions. AB - Compounds with two or more different pharmacodynamic activities in a single molecule are designated as hybrid drugs. If several stereoisomers with different pharmacodynamic activities exist in one molecule, the term pseudo-hybrid drug is applied. In the treatment of hypertension, the use of hybrid drugs enables a considerable reduction in the number of tablets to be taken per day. Conversely, the dose of each individual component cannot be tritrated. Most hybrid drugs used in antihypertensive treatment are beta-blockers with an additional vasodilator component, caused by different mechanisms such as alpha-adrenoceptor blockade, beta 2-adrenoceptor agonism, ACE inhibition or direct relaxation of vascular smooth muscle. Examples include labetalol (in fact, a mixture of four stereoisomers), carvedilol, celiprolol, dilevalol, tertatolol and BWA-575 C. A combination of beta-receptor blockade and vasodilation may be beneficial from a hemodynamic point of view. More recently it has been recognized that urapidil and ketanserin are hybrid drugs, each containing at least two pharmacodynamic activities in their molecules. PMID- 2200694 TI - The activation of serotonin receptors by tryptamine induces hyperinsulinemia in mice. AB - The effects of tryptamine on serum insulin levels were investigated. Tryptamine induced an apparent increase in serum insulin levels in mice. The elevation in insulin elicited by tryptamine was potently antagonized by the 5-HT1 and 5-HT2 receptor antagonist, methysergide, but partially reduced by the 5-HT2 receptor antagonist, ketanserin. However, the 5-HT3 receptor antagonist, ICS 205-930, was without effect. These results indicate that both 5-HT1 and 5-HT2 receptors are involved in the tryptamine-induced increase in insulin levels. PMID- 2200695 TI - Typing tools for the investigation of epidemic fungal infection. PMID- 2200696 TI - Numerical analysis of SDS-PAGE protein patterns of Serratia marcescens: a comparison with other typing methods. AB - Twenty-five cultures comprising 18 clinical isolates of Serratia marcescens from two hospitals, the type strain of S. marcescens, two reference strains of S. marinorubra, the type or a reference strain of three other Serratia species and a reference strain of undetermined species, were characterized by one-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of whole cell proteins. The protein patterns were highly reproducible and were used as the basis of a numerical analysis which divided the clinical isolates into eight protein types. Comparison with O-serotyping indicated that the level of discrimination by SDS-PAGE was similar. As with O-serotyping, a secondary scheme, such as phage typing, is necessary to differentiate strains of the same protein type. We conclude that high-resolution SDS-PAGE of proteins provides an effective adjunct to other methods for typing isolates of S. marcescens. PMID- 2200697 TI - Prevalence of verocytotoxigenic Escherichia coli in ground beef, pork, and chicken in southwestern Ontario. AB - Samples of ground beef (225), pork (235) and chicken (200) were randomly selected from meat processing plants in the southwestern Ontario area. Supernatants of broth cultures of the samples were tested for verocytotoxins using a Vero cell assay. Neutralization of cytotoxic activity using antisera specific for three types of verocytotoxin (Verotoxin 1, Verotoxin 2 and Shiga-like toxin II) was performed on positive samples. Isolation of verocytotoxigenic Escherichia coli (VTEC) was attempted from positive samples. VTEC were confirmed as E. coli biochemically, tested for drug resistance, and serotyped. Based on neutralization studies, the prevalence of VTEC in beef and pork was at least 36.4% and 10.6%, respectively. This is much higher than has been reported from a survey of retail meats in which a method designed to detect only E. coli O 157.H7 was used. Isolations of VTEC were made from 10.4% of the beef samples and 3.8% of the pork samples. No VTEC were recovered from the chicken samples. The majority of VTEC isolates were susceptible to commonly used antimicrobial agents. A number of the serotypes of the VTEC isolates recovered have been associated with human disease; however, no VTEC of serotype O 157.H7 were isolated. PMID- 2200698 TI - International increase in Salmonella enteritidis: a new pandemic? AB - Over the past 5 years Salmonella enteritidis infections in humans have increased on both sides of the Atlantic ocean. The WHO salmonella surveillance data for 1979-87 were reviewed and show that S. enteritidis appears to be increasing on at least the continents of North America, South America, and Europe, and may include Africa. S. enteritidis isolates increased in 24 (69%) of 35 countries between 1979 and 1987. In 1979, only 2 (10%) of 21 countries with reported data reported S. enteritidis as their most common salmonella serotype; in 1987, 9 (43%) of 21 countries reported S. enteritidis as their most common serotype; 8 (89%) of 9 were European countries. Although the reason for the global increase is not yet clear, investigations in individual countries suggest it is related to consumption of eggs and poultry which harbour the organism. PMID- 2200699 TI - Molecular characterization of trimethoprim resistance in Shigella sonnei in Sicily. AB - During the 3-year period 1985-7, all strains of Shigella sonnei isolated in Catania, Sicily, showed a high level of resistance to trimethoprim (Tp) which was invariably associated with resistance to other antibiotics. Plasmid analysis showed 18 different electropherotypes: 35 of 37 strains harboured a plasmid of 70 Megadaltons (MDa), and 29 of 37 strains a plasmid of 130 MDa. Restriction endonuclease fingerprinting of purified 70 MDa plasmid DNA from different strains demonstrated that these plasmids were similar but not identical. In some strains with transferable Tp resistance, DNA hybridization analysis demonstrated the presence of gene coding for the production of dihydrofolate reductase (DHFR) type V. In contrast, there was no detectable hybridization with DNA probes specific for genes coding for DHFR types I, II and IV. This is the first report of the DHFR type V gene outside Sri Lanka. PMID- 2200701 TI - Molecular epidemiology of Shigella infection in Central Australia. AB - Shigellosis is endemic in Central Australia and the infections are predominantly due to Shigella flexneri 6, Shigella flexneri 2a and Shigella sonnei. Plasmid profiles of isolates collected from 1985-9, suggested that infections caused by Shigella flexneri 6 were predominantly due to a single clone, whereas those caused by Shigella flexneri 2a and Shigella sonnei were due to several genetically diverse strains, although strains with identical plasmid profiles were found in widely separated geographical areas and in different years. PMID- 2200700 TI - Epidemiology of shigellosis in Teknaf, a coastal area of Bangladesh: a 10-year survey. AB - The epidemiological data on shigellosis in Teknaf, a coastal area of Bangladesh, were reviewed for a 10-year period (1975-84). Certain similarities and differences were observed in the epidemiology of the disease in Teknaf when compared with urban Dhaka and rural Matlab. Similarities included: round-the-year infection with two peaks, one in the monsoon period and the other in the winter period; high male to female attendance ratio at the treatment centre; the predominance of infection in the under-15-year age group; high mortality rate in the under-5-year age group of both sexes and in females of all age groups; the multiple drug resistance of organisms. Differences included the higher isolation rate of organisms in Teknaf (42.1% as against 11-12% in Dhaka and Matlab) and the preponderance of Shigella dysenteriae 1 infection in females in Teknaf. The unusually high isolation rate of shigella makes Teknaf the area with the highest incidence of shigellosis in Bangladesh. PMID- 2200702 TI - Plasmid profile analysis and antimicrobial susceptibility patterns of Shigella isolates from Nigeria. AB - In an epidemiological survey, plasmid profiles and antimicrobial susceptibility testing of 100 shigella isolates in Lagos, Nigeria was done. All the isolates were sensitive to nalidixic acid, nitrofurantoin and ciprofloxacin. The commonest antimicrobial susceptibility pattern was resistance to ampicillin, colistin sulphate, co-trimoxazole, streptomycin and tetracycline. All but 4 of 100 isolates screened contained one or more plasmids. Plasmid profile analysis distinguished more strains than did antimicrobial susceptibility patterns. A total of 36 isolates was able to transfer resistance plasmids to Escherichia coli K-12 by conjugation. Using in vitro transformation, seven isolates transferred resistance. These plasmids specified resistance to tetracycline, streptomycin, sulphonamide, trimethoprim and ampicillin. PMID- 2200703 TI - Plasmid profiles of antibiotic-resistant Shigella dysenteriae types 2, 3, 4, 6 and 7 isolated in Ethiopia during 1976-85. AB - Plasmid profile analysis by agarose gel electrophoresis was carried out on 37 drug-resistant strains of Shigella dysenteriae types 2, 3, 4, 6 and 7. These strains were collected between 1976 and 1985 in Addis Ababa, Ethiopia. The plasmid profile of S. dysenteriae type 2 strains with R-type CSSuT did not show middle-sized plasmids likely to code for CSSuT resistance. All strains contained a large plasmid of about 120 megadaltons (MDa), and a cryptic plasmid of about 2.2 MDa. The plasmid profiles of S. dysenteriae type 3 with R-types ACSSuT, SSuT and SSu showed a 4.2 MDa SSu-determinant, which was demonstrated in Escherichia coli K12 recipients resulting from triparental crosses. The ACT determinant in S. dysenteriae type 3 with R-type ACSSuT is probably chromosomally mediated. Cryptic plasmids of about 3.0 and 2.2 MDa were found in all S. dysenteriae type 3 isolates. The 4.2 MDa plasmid featured prominently in the plasmid profiles of S. dysenteriae types 4, 6 and 7 with R-types SSuT and SSu. However, this plasmid was not mobilizable by triparental crosses. There was a relative paucity of transferable plasmids in non-Shiga bacillus isolates. However, incompatibility group N plasmids, coding for tetracycline resistance, were detected. PMID- 2200704 TI - Drug-resistant coagulase-negative skin staphylococci. Evaluation of four marker systems and epidemiology in an orthopaedic ward. AB - Drug-resistant coagulase-negative staphylococci (DRCNS) in orthopaedic patients and ward staff were studied. A significant increase in the DRCNS carriage rate was observed among the 16 patients studied after 14 days of hospitalization with levels approaching that of the staff. Patients receiving dicloxacillin prophylaxis (n = 9) were more likely to be colonized with methicillin-resistant CNS, while patients receiving no antibiotics (n = 7) became to a larger extent colonized with multiple DRCNS. The combined data from species determination, biochemical, plasmid, and antibiogram typing revealed a considerable diversity among DRCNS; 64 types were distinguished among 112 DRCNS isolates selected for study after exclusion of apparently duplicate isolates. Plasmid plus antibiogram typing yielded almost as many types (61); whereas species determination plus antibiogram distinguished only 33 types. Although a novel computerized 96 reaction biotyping method alone enabled differentiation of 17 biotypes, most DRCNS isolates belonged to one of three major biotypes limiting the usefulness of this method. Ten of the 64 (16%) DRCNS types identified comprised 50 of the 112 (45%) isolates. These were isolated from staff and from patients on day 14, suggesting a nosocomial origin. PMID- 2200705 TI - Posttranslational attenuation of peptide gene expression. AB - Studies of the cell-specific processing of neuroendocrine peptides have shown that neuroendocrine cells occasionally fail to mature the biosynthetic precursors to bioactive peptides, or that they do so to a negligible extent only. Instead, inactive precursors and processing intermediates accumulate in the cells. Thus, the expression of genes encoding hormonal peptides is in certain cells and under certain conditions attenuated at the postranslational level. The exact molecular mechanisms of posttranslational attenuation are still largely unknown. The review emphasizes that posttranslational attenuation may play a significant role during normal cell differentiation and in the carcinogenic transformation of cells. The existence of postal attenuation may play a significant role during normal cell differentiation and in the carcinogenic transformation of cells. The existence of post-translational attenuation has significant biological and clinical implications. PMID- 2200706 TI - Exercise training increases glucose transporter protein GLUT-4 in skeletal muscle of obese Zucker (fa/fa) rats. AB - The present study examined the level of GLUT-4 glucose transporter protein in gastrocnemius muscles of 36 week old genetically obese Zucker (fa/fa) rats and their lean (Fa/-) littermates, and in obese Zucker rats following 18 or 30 weeks of treadmill exercise training. Despite skeletal muscle insulin resistance, the level of GLUT-4 glucose transporter protein was similar in lean and obese Zucker rats. In contrast, exercise training increased GLUT-4 protein levels by 1.7 and 2.3 fold above sedentary obese rats. These findings suggest endurance training stimulates expression of skeletal muscle GLUT-4 protein which may be responsible for the previously observed increase in insulin sensitivity with training. PMID- 2200707 TI - Inactivation of thioredoxin by sulfite ions. AB - Oxidized thioredoxin undergoes sulfitolysis of its single disulfide bond at low concentrations of sulfite ions and protein and in the absence of denaturing agents. The reaction, which has an optimum at pH 8, was studied using [35S]sulfite and E. coli thioredoxin as model. The product, thioredoxin-S sulfonate, has a half-life of several hours in solution. It is unable to activate chloroplast NADP malate dehydrogenase. Thioredoxin sulfitolysis may therefore be a physiologically important factor in mediating the phytotoxic effects of sulfur dioxide in plants. PMID- 2200708 TI - Endothelin stimulates hypertrophy and contractility of neonatal rat cardiac myocytes in a serum-free medium. AB - The effect of endothelin (ET) on rat cardiac myocytes cultured in a serum-free, defined medium was determined. ET simulated cardiac myocyte hypertrophy in a dose dependent manner as determined by the protein synthesis and cell surface area. Since the myocyte hypertrophy was abolished by H-7, a protein kinase C inhibitor, ET-receptor mediated protein kinase C activation may be involved in cardiac myocyte hypertrophy. At the same time, ET also stimulated myocyte contractility in this medium, and this stimulatory effect was inhibited by nicardipine. This result indicates that the influx of extracellular calcium ion is necessary for the stimulation of contractility induced by ET. PMID- 2200710 TI - The environments of Trp-248 and Trp-330 in tryptophan indole-lyase from Escherichia coli. AB - The two tryptophan residues, Trp-248 and Trp-330, in tryptophan indole-lyase (tryptophanase) from E. coli have been separately mutated to phenylalanine using site-directed mutagenesis. Both single tryptophan mutant enzymes have full catalytic activity, but exhibit different fluorescence and near-UV circular dichroism spectra. These results indicate that Trp-330 is more deeply buried than is Trp-248, and is in a more asymmetric environment. Neither residue reacts with N-bromosuccinimide (NBS), although tryptophan indole-lyase is inactivated by NBS. These results demonstrate that the tryptophan residues in tryptophan indole-lyase are not catalytically essential. PMID- 2200709 TI - Grapevine stilbene synthase cDNA only slightly differing from chalcone synthase cDNA is expressed in Escherichia coli into a catalytically active enzyme. AB - Stilbene synthase is responsible for the formation of resveratrol and other stilbenes which function in grapevine as phytoalexins. A full-length stilbene synthase cDNA was prepared from grapevine mRNA and sequenced. The insert in pSV25 coding for a polypeptide with 392 amino acids was inserted into the vectors pKK233-2 and pDS12/RBSII-2, respectively. Expression of the cDNA in Escherichia coli yielded an enzymatically active dimer exhibiting solely stilbene synthase activity. The protein was characterized by enzyme activity and Western blot analysis. PMID- 2200712 TI - Eukaryotic DNA methylation: facts and problems. AB - Patterns of DNA methylation in complex genomes like those of mammalian cells have been viewed as indicators of different levels of genetic activities. It is as yet unknown how these complicated patterns are generated and maintained during cell replication. There is evidence from many different biological systems that the sequence-specific methylation of promoters in higher eukaryotes is one of the important factors in controlling gene activity at a long-term level. In general, the fifth nucleotide 5-methyldeoxycytidine can be considered as a modulator of protein-DNA interactions. The degree and direction of this modulation has to be assessed experimentally in each individual instance. The establishment of de novo patterns of DNA methylation is characterized by the gradual non-random spreading of DNA methylation by an essentially unknown mechanism. In this review, some of the general concepts of DNA methylation in mammalian systems are presented, and research currently performed in the authors' laboratory has been summarized. PMID- 2200711 TI - Sub-site preferences of the aspartic proteinase from the human immunodeficiency virus, HIV-1. AB - A series of synthetic, chromogenic substrates for HIV-1 proteinase with the general structure Ala-Thr-His-Xaa-Yaa-Zaa*Nph-Val-Arg-Lys-Ala was synthesised with a variety of residues introduced into the Xaa, Yaa and Zaa positions. Kinetics parameters for hydrolysis of each peptide by HIV-1 proteinase at pH 4.7, 37 degrees C and u = 1.0 M were measured spectrophotometrically and/or by reverse phase FPLC. A variety of residues was found to be acceptable in the P3 position whilst hydrophobic/aromatic residues were preferable in P1. The nature of the residue occupying the P2 position had a strong influence on kcat (with little effect on Km); beta-branched residues Val or Ile in this position resulted in considerably faster peptide hydrolysis than when e.g. the Leu-containing analogue was present in P2. PMID- 2200713 TI - Gene expression during tuber development in potato plants. AB - Potato tubers are modified stems that have differentiated into storage organs. Factors such as day-length, nitrogen supply, and levels of the phytohormones cytokinin and gibberellic acid, are known to control tuberization. Morphological changes during tuber initiation are accompanied by the accumulation of a characteristic set of proteins, thought to be involved in N-storage (i.e. patatin) or defense against microbial or insect attack (i.e. proteinase inhibitor II). Additionally, deposition of large amounts of starch occurs during tuber formation, which is paralleled by an increase in sucrose synthase and other enzymes involved in starch biosynthesis (i.e. ADP-glucose pyrophosphorylase, starch synthases, and branching enzyme). Potential controlling mechanisms for genes expressed during tuberization are discussed. PMID- 2200714 TI - The role of introns in evolution. AB - What are the roles of 'classical' introns in the evolution of nuclear genes, and what was the origin of these introns? Exon shuffling has been important in the evolution of cell surface and extracellular proteins, but the evidence for it in respect of intracellular proteins is weak. Intron distributions imply that some introns have been removed while others have been inserted in the course of evolution: ancestral patterns of introns may thus have been obscured. Recent evidence on the self-splicing and reverse-splicing abilities of Group II introns supports the hypothesis that these could have been the ancestors of classical introns. PMID- 2200715 TI - Proteins under extreme physical conditions. AB - Life on earth is ubiquitous within the limits from -5 to 110 degrees C for temperature, 0.1 to 120 MPa for hydrostatic pressure, 1.0 to 0.6 for water activity and pH 1 to 12. In general, mutative adaptation of proteins to changing environmental conditions tends to maintain 'corresponding states' regarding overall topology, flexibility and hydration. Due to the minute changes in the free energy of stabilization responsible for enhanced stability, nature provides a wide variety of different adaptative strategies. In the case of thermophilic proteins, improved packing densities are crucial. In halophilic proteins, decreased hydrophobicity and clustered surface charges serve to increase water and salt binding required for solubilization at high salt concentration. In the case of barophiles, high-pressure adaptation is expected to be less important than adaptation to low temperatures governing the deep sea. Nothing is known with respect to the mechanisms underlying psychrophilic and acidophilic/alkalophilic adaptation. PMID- 2200716 TI - Protein kinase C in transmembrane signalling. AB - Protein kinase C functions as the transducer of a second messenger, diacylglycerol, and is the major receptor for tumour-promoting phorbol esters. The enzyme is a family of proteins with closely but distinct structures and individual enzymological properties. Members of the family are differently distributed in particular cell types and limited intracellular locations from lower organisms to mammalian tissues. The enzyme appears to interact with many signalling pathways, and display functions in the processing and modulation of cellular responses to external stimuli. Presumably, each member of the family plays discrete roles in the control of a variety of membrane functions and activation of gene transcription. PMID- 2200717 TI - Enzyme-enzyme interactions and their metabolic role. AB - There are continuing reports on the existence of complexes of sequential metabolic enzymes. New techniques for their detection have been described and include affinity electrophoresis and the use of anti-idiotypic antibodies. Channeling of substrates has been reported for several systems as well as direct substrate transfer through dynamic enzyme associations. Kinetic parameters of metabolic control of organized systems have been formulated and tested in several systems. These recent results are expanding our understanding of metabolic processes and their control. PMID- 2200718 TI - Protein kinase C in insulin releasing cells. Putative role in stimulus secretion coupling. AB - The evidence for the involvement of protein kinase C (PKC) in insulin secretion stimulated by glucose and Ca2(+)-mobilizing receptor agonists has been reviewed. Results of phorbol ester binding to intact cells and the measurements of the proportion of PKC associated with the membrane after cell fractionation are presented. Glucose stimulation leads to increased phorbol ester binding without causing membrane insertion of the enzyme which, however, occurs with receptor agonists. It is suggested that the rise in cytosolic Ca2+ in response to glucose favours the apposition of PKC to the membrane whereas intercalation of the enzyme requires phospholipase C-mediated generation of diacylglycerol. It is possible that this effect of glucose on PKC, although not involved in the initiation of secretion, could explain the potentiation of insulin release observed in the presence of the receptor agonists. PMID- 2200719 TI - Antibiotics--cloning of biosynthetic pathways. AB - Biosynthetic pathways leading to antibiotics have often been found to be clustered, and new organizational forms of multifunctional enzymes have been discovered. Such polyenzymes accomplish the synthesis of complex metabolites such as peptides or polyketides by a sequence of enzymatic reactions. So, reactions leading to the tripeptide precursor of beta-lactam antibiotics, ACV, or to the cycloundecapeptide cyclosporine have been fused into single polypeptide chain synthetases, respectively. In certain isofunctional sites restricted similarities have been detected. PMID- 2200720 TI - Insertion and translocation of proteins into and through membranes. AB - In prokaryotic and eukaryotic organisms, proteins are efficiently sorted to reach their final destinations in a whole range of subcellular compartments. Targeting is mediated by hydrophobic signal sequences or hydrophilic targeting sequences depending upon the compartment, these sequences being often processed. Proteins cannot be translocated through a membrane in a tightly folded stage, they must have a loose conformation, the so-called 'translocation competent state', which is usually kept through interactions with chaperones. In addition to these cytosolic receptor-like components, receptors are also present on the target membranes. Depending upon the organelles and organisms, two different energy sources have been identified, energy rich phosphate bonds (ATP and GTP) and a potential across the target membrane. Besides the signal peptides, various classes of signals have been identified to account for topologies of membrane proteins. Protein secretion in bacterial organisms has been extensively studied. Various classes of proteins use different strategies, some of these may also be used in eukaryotic cells. PMID- 2200722 TI - Index of Biochemical Reviews 1989. PMID- 2200721 TI - Nitrogen fixation genes involved in the Bradyrhizobium japonicum-soybean symbiosis. AB - The symbiotic nitrogen fixation genes (nif, fix) of Bradyrhizobium japonicum, the root nodule endosymbiont of soybean, are organized in at least two separate chromosomal gene clusters. These genes code for proteins of the nitrogenase complex, for proteins involved in their assembly with cofactors and for putative electron transport functions. One gene, nifA, codes for a transcriptional regulatory protein that plays a central role in the control of expression of the other genes in response to the cellular oxygen status. Only at low partial pressures of O2 will the target promoters be activated by NifA. PMID- 2200723 TI - [Role of the submandibular glands in in vivo mechanisms of plasma inactive renin release in the rat]. AB - In our present studies, we evaluated the role of the submandibular glands (SMG) on plasma inactive renin (PIR) releasing mechanisms in rats using some agents which are known to stimulate plasma active renin (PAR) release. The results were analyzed between sialoadenectomized (SX) and sham-operated (control: C) rats. Twenty-four h after the operation, PAR releasing agents, furosemide (FRO) 2.5 mg/rat/h with prior iv bolus 5 mg, captopril (CAP) 5 mg/rat/h with prior iv bolus 10 mg, 1-Sar-8-Ile-angiotensin II (Ang II A) 300 ng/kg/min, prostaglandin E1 (PGE1) 100 ng/kg/min, and prostaglandin I2 (PGI2) 100 ng/kg/min, were infused through femoral venous cannulae. Blood samples were taken through femoral arterial cannulae into test tubes containing 2 mg EDTA-2Na. PAR was assayed by RIA, and total renin was obtained after tryptic activation. According to the responses of PIR, the agents used were categorized into three patterns: FRO increased PIR, both PGs lowered PIR, and, CAP and Ang II A had no effect on PIR release. The PIR release mechanisms by FRO were further investigated by 20 mg FRO ip injection in totally nephrectomized rats. PIR increased even in nephrectomized rats, but the increase was totally canceled by the following SX. In conclusion, FRO alone among some agents studied is able to stimulate PIR release only under the existence of SMG. PMID- 2200724 TI - Ultrastructural study on the erythrocytic schizogony of Plasmodium vivax. AB - Erythrocytic schizogony is initiated by repeated division of the nucleus in rapid sequence. Another important feature of the developing schizont is the reappearance of segments of thick inner membrane and formation of lobes around these segments. These bulbous protuberances signal the start of budding process which ends in complete segmentation of the cell. The cytoplasmic organelles which de-differentiate at the beginning of trophozoite stage are formed again. Asynchrony during merozoite formation is observed in some schizonts where fully mature merozoites are seen lying in the parasitophorous vacuole while the mother cell is still in the process of giving rise to new merozoites. PMID- 2200725 TI - Micro in vitro assessment of Plasmodium falciparum sensitivity to chloroquine and mefloquine in Gujarat. AB - Micro in vitro tests conducted in 1987 in Surat district of Gujarat on sensitivity status of P. falciparum to chloroquine and mefloquine revealed that the parasite has developed resistance to chloroquine upto 32 pmol. The ED 99 in Hazira, Gothan and Umra areas of the district was found to be 17.3, 18.5 and 8.7 pmol/well for chloroquine and for mefloquine it was 14.5, 4.8 and 6.8 pmol/well respectively. Monitoring of P. falciparum resistance is indicated under National Malaria Eradication Programme. PMID- 2200726 TI - Radical treatment of vivax malaria in Madhya Pradesh, India. PMID- 2200727 TI - Effect of insulin therapy on metabolic fate of apolipoprotein B-containing lipoproteins in NIDDM. AB - Non-insulin-dependent diabetic (NIDDM) subjects exhibit abnormalities in their plasma lipid and lipoprotein profiles that increase the risk of ischemic heart disease. This study was designed to examine the metabolic behavior of very-low density (VLDL), intermediate-density (IDL), and low-density (LDL) lipoproteins in NIDDM patients before treatment and after 4 wk of insulin therapy. Basal turnover studies of 131I-labeled VLDL1 (svedberg units [Sf] 60-400) and 131I-labeled VLDL2 (Sf 20-60) apolipoprotein B (apoB) were conducted in a group of seven NIDDM patients who had been off oral therapy for 1 wk. The subjects exhibited higher than normal transport rates for VLDL1 and a diminished input of apoB into the VLDL2 density range. These observations are concordant with the hypothesis that NIDDM patients overproduce VLDL triglyceride but not apoB. VLDL1 and VLDL2 were converted to IDL and ultimately to LDL at approximately normal rates, although the delipidation pathway by which apoB-containing particles were processed exhibited different properties from that seen in control subjects. Insulin therapy reduced plasma triglyceride by 38%, and this was associated with a 41% fall in VLDL1 mass (P less than 0.01). VLDL2 was less affected (19% reduction, P less than 0.05), IDL was unchanged, and LDL fell 17% (P less than 0.05). Repeat metabolic studies revealed that the major effects of insulin were to reduce VLDL1 apoB transport (from 811 to 488 mg/day) and increase the direct input of VLDL2 into the plasma (from 182 to 533 mg/day, P less than 0.05). These alterations in VLDL production led to normalization of apoB kinetics in IDL and LDL. The fractional catabolic rate of LDL increased 19% (P less than 0.05), whereas direct input into this fraction, which had been high before treatment, was reduced. Postheparin plasma lipoprotein lipase (LPL) and hepatic lipase levels were unaffected by insulin, although the hormone did increase LPL in adipose tissue. This lack of effect on lipase activities correlated well with the observation that the rates of catabolism of apoB in VLDL1, VLDL2, and IDL were not significantly affected by insulin therapy. PMID- 2200728 TI - Equivalent in vivo biological activity of insulin analogues and human insulin despite different in vitro potencies. AB - In vivo biological potency of two human insulin analogues, AspB9,GluB27 insulin and AspB10 insulin with low and high affinity to the insulin receptor, respectively, was assessed by intravenous infusion of equimolar amounts in pigs, with the euglycemic clamp technique. Human insulin and the low- and high-affinity analogues showed equivalent glucose utilization rates in the steady state (mean +/- SE 14.7 +/- 1.4, 12.7 +/- 1.5, and 12.2 +/- 1.2 mg.kg-1.min-1, respectively; n = 7). The corresponding plasma insulin levels, however, were markedly different (329 +/- 25 and 856 +/- 46 pM, P less than 0.05; 197 +/- 19 pM, P less than 0.05). There was an inverse relationship between the insulin levels and the in vitro activities measured by binding to human hepatoma cells (HepG2; 100, 20, and 308%) or by incorporation of glucose into lipids in mouse free fat cells (100, 31, and 207%). The total amount of glucose infused during and after insulin infusion was equal for the three insulins, whereas glucose utilization as a function of time was somewhat different. By describing the individual plasma concentration courses with an open two-compartment model with elimination from the receptor compartment, the time courses for binding and elimination of the three insulins in the receptor compartment were estimated. The effect seems closely linked to the elimination of insulin from the receptors rather than to the amount of insulin bound to the receptors. In conclusion, the total effect of equimolar amounts of human insulin and the two insulin analogues on glucose utilization is equal regardless of the different receptor affinities of the insulins. PMID- 2200729 TI - Recognition of common islet antigen by autoantibodies from NOD mice and humans with IDDM. AB - Previous studies showed that islet cell autoantibodies are present at the onset of insulin-dependent diabetes mellitus (IDDM) in humans and in rodent models of this disease. The targets of these antibodies are not well characterized. Using an immunoblot assay on protein extracts from rat insulinoma (RIN) cells (RINm5F), we showed that serums from nonobese diabetic (NOD) mice bind to a 52,000-Mr islet cell antigen. Nondiabetic NON mice do not have antibodies to this antigen. The NOD and NON serums also contained antibodies to salivary gland proteins. Analysis of the tissue distribution of the 52,000-Mr antigen revealed that it is present in purified RINm5F membranes but is not found in other endocrine or nonendocrine tissues. Autoantibodies to an antigen of similar molecular weight are detected in 29% of human IDDM serums. To determine whether the autoantibodies from mouse and human serums bind the same antigen, two-dimensional immunoblots were carried out. The 52,000-Mr protein isoforms appeared identical when probed with NOD and human IDDM serums. We conclude that serums from NOD mice and some humans with IDDM contain similar autoantibodies to a 52,000-Mr RINm5F cell-specific membrane protein. The presence of autoantibodies to this 52,000-Mr islet cell protein at the onset of the disease suggests that it may be an important antigen in IDDM. PMID- 2200730 TI - Effect of insulin on glucose utilization in epitrochlearis muscle of rats with streptozocin-induced NIDDM. AB - Because skeletal muscle plays a major role in glucose disposal, it may be the primary site of insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM). Rates of glycogen synthesis (GS), glucose utilization via glycolysis, glycolytic utilization (GU), and glucose transport (GT) were studied in epitrochlearis muscles (EMs) obtained from 10-wk-old nonfasted Sprague-Dawley rats in which NIDDM was neonatally induced with streptozocin. Plasma glucose in NIDDM rats was elevated (P less than 0.001), whereas plasma insulin was similar in NIDDM and control rats. No differences in muscle weight, protein, glycogen, ATP, phosphocreatine, lactate, lactate-pyruvate ratios, or glucose-6-phosphate were noted in EMs of control and NIDDM rats. EMs were incubated in medium containing 5.6 or 11.2 mM glucose with tracer D-[5-3H]glucose and insulin from 0 to 7.18 x 10(-7) M for 1 or 2 h, and GS, GT, and GU were evaluated. Similar rates of basal (non-insulin-mediated) and insulin-stimulated GS, GU, and GT were observed in EMs of NIDDM and control rats incubated in 5.6 mM glucose for 2 h. Insulin dose-response curves revealed similar sensitivities and responsiveness. Increasing glucose concentration (from 5.6 to 11.2 mM) induced significant increases in basal rates of GS, GU, and GT in EMs of control but not NIDDM rats. Insulin dose-response curves for GS and GT revealed decreased sensitivity and no change in responsiveness in EMs of control and NIDDM rats, even though GU of EMs of NIDDM rats was significantly lower at basal and all other insulin concentrations. These data revealed that both insulin resistance and glucose resistance contribute to the impaired glucose metabolism in EMs of the NIDDM rat. PMID- 2200731 TI - Islet cell antibodies as predictive markers for IDDM in children with high background incidence of disease. AB - To determine the prevalence and predictive value of islet cell antibodies (ICAs) for the development of insulin-dependent diabetes mellitus (IDDM) in 1212 Finnish children aged 3-18 yr, samples for ICA determination were taken in 1980, and subsequent analyses were performed in originally ICA+ children and in 296 initially ICA- children in 1983 and 1986. All 1212 subjects were followed for 8 yr for the development of IDDM. Fifty children (4.1%) were positive for conventional ICAs (IF-ICAs) in 1980 (range 3-80 Juvenile Diabetes Foundation units [JDF U]; median 30 JDF U), of which 12 (1.0%) had complement-fixing ICAs (CF-ICAs) in their serums (range 3-30 JDF U; median 8 JDF U). None were exclusively CF-ICA+. Boys were CF-ICA+ more often than girls (9 of 563 [1.6%] vs. 3 of 649 [0.5%], respectively; P less than 0.05). Over the next 6 yr, 4 of 39 subjects lost their IF-ICAs, and 4 of 12 lost their CF-ICAs without progressing to diabetes. The initial IF-ICA levels in these subjects were lower (range 3-8 JDF U; median 7 JDF U; P less than 0.05) than those in the persistent cases. In the initially ICA- subgroup (n = 296), 7 subjects (2.4%) later became IF-ICA+, and 4 (1.4%) became CF-ICA+. The levels of ICA in these subjects were lower than in the originally ICA+ ones (P less than 0.05), and 3 IF-ICA+ and 2 CF-ICA+ subjects again became ICA- before 1986.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2200732 TI - Computer-assisted curriculum for medical students on early diagnosis of substance abuse. AB - A computer-assisted curriculum on early diagnosis of substance abuse was developed for third-year medical students on their required family medicine rotation. Three computer-assisted instruction modules on early diagnosis, attitudes, and screening questionnaires were followed by two conferences: 1) a discussion and review session, and 2) a tutorial and role playing on engaging patients with substance abuse in treatment. Finally, students identified an ambulatory patient at risk for substance abuse and performed an evaluation. All 33 unselected students gave high ratings to all of the learning activities and the entire curriculum. Almost all were satisfied with the emphasis on substance abuse in their clerkship and expressed motivation to learn more. Student acceptance of teaching on substance abuse can be attained by a curriculum in which goals, objectives, and expectations are delineated clearly; in which the content is clinically relevant; which uses computer-assisted instruction, role playing, and a clinical exercise to stimulate problem-solving and skill development; in which conferences are discussion oriented; and for which pretests are used to promote learner receptivity. PMID- 2200733 TI - Health promotion for elderly patients. AB - A review of the literature on health promotion for the elderly reveals that changes in behavior, recognized as beneficial if made early in life, also increase longevity and quality of life if made in one's later years. National survey data show that although people over 65 years are less likely to have harmful health and nutritional habits than are middle-aged adults, they are also less aware of the effect of behavioral patterns on health. Physician- and patient provided data indicating that education and screening exams are provided less frequently to the elderly suggest possible age-related deficits in health promotion and preventive care. Expansion of physicians' efforts aimed at health promotion for the elderly could reduce morbidity and improve quality of life for this growing population by delaying the onset of dependency. PMID- 2200734 TI - Normative data: their definition, interpretation, and importance for primary care physicians. AB - Normative data, data that characterize what is usual in a defined population at a specific point or period of time, are of enormous importance to primary care physicians. Such data, which seek to describe rather than explain phenomena, are essential for: a) describing the natural history of clinical conditions in the community; b) developing standards of care for primary physicians; and c) establishing illness nosologies appropriate for primary care research. In all studies designed to obtain normative data, methodologic issues need careful attention. For some purposes, normative data may be quickly obtained in cross sectional studies. When age effects are to be described or when time is an important consideration, longitudinal study designs may be needed to evaluate potential cohort effects and epoch effects. Especially important in studies which seek normative data are precise characterization of the study population, clear definition and measurement of phenomena, and appropriate interpretation and generalization of results. PMID- 2200735 TI - Parallel process in the family medicine system: issues and challenges for resident training. AB - This article uses the concept of parallel process to examine resident training as one component in a system of interlocking relationships. Parallel process is defined, and its applicability to the dynamic exchange of help-seeking and help giving behaviors which lies at the core of the health care system is examined. The concept of stages or phases in parallel process development next is explored. A relational model for optimal functioning between resident-patient and attending resident is proposed, as well as an illustrative examination of one of the more problematic issues which a parallel process analysis can bring to light. Therapeutic interventions to enhance help-giving and help-seeking at different levels of the system are defined and analyzed, and educational implications for resident training are summarized. PMID- 2200736 TI - Pan: a transcriptional regulator that binds chymotrypsin, insulin, and AP-4 enhancer motifs. AB - Two cDNAs were cloned that encode proteins (Pan-1 and Pan-2, with predicted molecular masses of 67.4 and 67.7 kD, respectively) that bind to a conserved transcriptional regulatory element present in pancreatic exocrine genes. The cDNAs are virtually identical in the region that encodes the amino-terminal 525 amino acids; they differ only by a 3-nucleotide insertion that results in the addition of a single amino acid. The cDNAs, however, code for related, but divergent, carboxy-terminal regions. Expression of the cloned cDNAs in HeLa cells activates expression of a cotransfected chimeric gene containing multimers of the pancreatic conserved element linked to a minimal promoter. Pan-1 and Pan-2 bind to the consensus sequence CAC/GCTGT/C, the CACCTGTC motif, which is present in transcriptional control elements of several genes. Both Pan-1 and Pan-2 bind to related motifs present in the rat insulin enhancer as well as a DNA segment containing the SV40 AP-4 element. The Pan-1 and Pan-2 cDNAs display extensive sequence identity with partial cDNA clones encoding E12 and E47, which bind to the immunoglobulin kappa E2 cis-active element, and may be derived from the same gene. These factors belong to a set of genetically distinct molecules, including AP-4 and MLTF, that bind to the CACCTGTC motif or related sequences. The Pan/E12,E47 proteins also show structural similarity with the Drosophila daughterless protein, MyoD, Myogenin, and Myf-5. PMID- 2200737 TI - Casein kinase II enhances the DNA binding activity of serum response factor. AB - Serum response factor (SRF) is a mammalian transcription factor that binds to the serum response element in the enhancer of the c-fos proto-oncogene and thus may mediate serum-induction of c-fos transcription. We report here that the DNA binding activity of recombinant SRF made in Escherichia coli can be greatly enhanced by incubation of the protein with HeLa cell nuclear extract. The enhancing activity is ATP or GTP dependent and cofractionates with a protein kinase that phosphorylates SRF on a specific tryptic peptide. Coincubation with phosphatase blocks the enhancing activity, further suggesting that the enhanced binding activity is due to phosphorylation. The specific tryptic phosphopeptide phosphorylated in vitro is also phosphorylated in vivo, demonstrating that this phosphorylation is physiologically important. We have localized the phosphorylation site by a small deletion mutant. Finally, we show that the kinase activity is provided by casein kinase II (CKII) or a close variant. The potential role of CKII as either a regulatory or constitutive modifier of SRF in vivo will be discussed. PMID- 2200738 TI - Cell-cycle-regulated phosphorylation of DNA replication factor A from human and yeast cells. AB - Replication factor A (RF-A) is a multisubunit, cellular protein that functions with SV40 T antigen during the initiation stage of DNA replication at the SV40 origin. It also cooperates with other replication factors to stimulate the activity of both polymerases alpha and delta during chain elongation. RF-A from both human and yeast cells is phosphorylated in a cell-cycle-dependent manner; the protein is phosphorylated at the G1- to S-phase transition, and dephosphorylation occurs at mitosis, thereby resetting this cycle. This observation provides a direct link between a protein required for DNA replication and cell-cycle-regulated protein phosphorylation. PMID- 2200739 TI - [Hygienic aspects of prevention of unfavorable effects of vibration on the population (review of the literature)]. PMID- 2200740 TI - [Hygienic problems of using ceolites in communal blood supply systems (review of the literature)]. PMID- 2200741 TI - [Radiation-hygienic significance of gas-aerosol discharge of coal thermoelectric plants (review of the literature)]. PMID- 2200742 TI - [European Economic Community and environmental protection (review of the literature)]. PMID- 2200743 TI - [Hygienic significance of low humidity under the conditions of Extreme North (review of the literature)]. PMID- 2200744 TI - Disproportionate-share payment sparks policy debate. AB - Despite a recent Congressional Budget Office report questioning the need for Medicare's disproportionate-share adjustment for many hospitals, federal lawmakers not only continue to support the add-on but hope to increase it in FY 1991. However, congressional debate over the issue was widened to include some fundamental questions about the original legislative intent of creating the disproportionate-share payments and what such funding is used for today. PMID- 2200745 TI - Former governor advocates health care rationing. PMID- 2200746 TI - Communicating hospital goals fosters support, says exec. PMID- 2200747 TI - HCFA tries new strategy to recoup Medicare payments. PMID- 2200748 TI - Response of monkeys to vaccination with recombinant vaccinia virus which coexpress HIV gp160 and human interleukin-2. AB - Immunization of two macaque monkeys with recombinant vaccinia viruses encoding the env gene of HIV-1 (VV-gp160) resulted in demonstrable levels of gp160, gp120 and gp41-specific immunoglobulins in both animals. The virus used to immunize one of the monkeys additionally expressed the human IL-2 gene, which encoded human IL 2 (VV-gp160-IL-2). No toxic side-effects of vaccine-delivered IL-2 were observed. Despite marked attenuation of virulence by the coexpressed lymphokine, the levels of vector-specific antibodies in both animals were similar. Some differences in the HIV-specific reactivity patterns were detected. Serum reactivity of monkey #A56 (VV-gp160) was directed against gp41, whereas monkey #B58 (VV-gp160-IL-2) showed a wider range of recognition, with higher antibody titres against the HIV lysate preparation. Furthermore, this study demonstrates the capacity to boost antibody responses to the vector and coexpressed HIV antigens in primates which are already immune. PMID- 2200749 TI - Study of human epithelial cell detachment and damage: effects of proteases and oxidants. AB - Polymorphonuclear leucocyte (PMN) accumulation is associated with damage to airways epithelial cells in bronchitis, bronchiectasis and some forms of asthma. PMNs release several molecules which may mediate this damage, particularly proteases and oxidants. Using an in vitro model of intact human amnionic epithelial cells (EC) attached to native basement membrane (BM), we evaluated the capacity of several proteases and oxidants to induce detachment of EC from the BM. Maximum desquamation was observed with collagenase, elastase and trypsin, with minimum effective concentrations required to produce 50% EC-desquamation (MEC50) for highly purified collagenase, pancreatic elastase, human leucocyte elastase, human leucocyte cathepsin-G (Cath-G), trypsin, and kallikrein being 3616 +/- 989 U/mL, 32.3 +/- 14.7 U/mL, 85.8 +/- 26.7 U/mL, 360 +/- 20 U/mL, 340 +/- 49 BAEE U/mL and 300 +/- 23 U/mL, respectively. Urokinase (20 U/mL) and plasmin (500 U/mL) produced no desquamation in this system. Relatively high concentrations of oxidants also produced detachment (MEC50 for H2O2 and HOCl being 0.59 +/- 0.006 mol/L and 0.015 +/- 0.009 mol/L, respectively) and pretreatment of EC membranes with non-detaching concentrations of H2O2 rendered them 10-fold more susceptible to protease-induced desquamation, suggesting synergism. Reduced glutathione (GSH), N-acetyl cysteine (NAC), ethylenediamine tetra-acetic acid (EDTA) and 1,10 phenanthroline ablated collagenase induced EC detachment. Elastase induced detachment was sensitive to inhibition by phenyl methyl sulfonyl fluoride (PMSF) and alpha 1-anti-proteinase (alpha 1-AP) and, to a lesser extent by aprotinin; trypsin-induced detachment was ablated by PMSF, alpha 1-AP and soybean trypsin inhibitor (SBTI) but not by 1,10 phenanthroline or EDTA. Cath-G induced detachment was profoundly inhibited by SBTI, GSH and NAC. These data demonstrate that human EC can be detached from intact BM by several PMN products, including collagenase, Cath-G and elastase, and that PMN-mediated detachment can be prevented by Cath-G and collagenase inhibitors. The data suggest a role for proteases, particularly Cath-G and collagenase, plus oxidants in synergism with proteases, in mediating PMN-induced EC detachment. PMID- 2200750 TI - Dynamics of positive and negative selection in the thymus: review and hypothesis. AB - T cells recognize with a single receptor both a product of antigens processed by antigen presenting cells (APC1) and a self-marker molecule, encoded by the major histocompatibility complex (MHC, a property termed MHC-restricted recognition of antigen). During their differentiation in the thymus, T cells "learn" what to regard as self-MHC molecules, and only the cells once able to recognize antigen in the context of self-MHC will be "positively selected" to exit the thymus. The cells, once capable of reacting to self molecules, do not exit the thymus. They are "negatively selected" (deleted). Both "positive" and "negative" selection depends on the T-cell-receptor (TCR) specificity. Furthermore, the TCR specificity determines the final phenotype of the mature T cells; namely, the cells with receptors specific for the MHC-class I molecule will acquire the CD4 CD8+ phenotype, while the cells with receptors specific for the MHC-class II molecule will acquire the CD4+CD8- phenotype. However, a few mature T cells in the periphery do not follow the rule: CD4 expression class II restriction and CD8 expression class I restriction. We believe that these T lymphocytes have a receptor with very high affinity for one class of MHC molecules and cross-react with another class of MHC molecules (with somewhat lower affinity). The majority of T lymphocytes with such receptors bind the thymic MHC molecule, for which they have the highest affinity. Since this affinity is too high for further differentiation, such clones are deleted in the thymus. However, a small fraction of these cells bind the alternative class of MHC molecules, due to cross reactivity of their receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2200751 TI - Coding region structure of interleukin-8 gene of human lung giant cell carcinoma LU65C cells that produce LUCT/interleukin-8: homogeneity in interleukin-8 genes. AB - A 1.9-kb fragment containing an interleukin-8 (IL-8) coding region was amplified by the polymerase chain reaction (PCR) from the genomic DNA of human lung giant cell carcinoma LU65C cells that produce LUCT/IL-8 with N-terminal sequence of AVLPR. The coding region was found to consist of 4 exons and 3 introns as identical as that of the gene of MDNCF/IL-8 lacking N-terminal AVLPR. PCR using genomic DNAs from human polymorphonuclear leukocytes and mononuclear cells also provided the same 1.9-kb fragment as that from LU65C genomic DNA. Thus, it seems likely that human cells possess IL-8 genes with the homogeneous coding region so that they may first produce the same mature protein with N-terminal AVLPR (= LUCT) which was then truncated. PMID- 2200752 TI - In situ demonstration of Mycobacterium leprae antigens in leprosy lesions using monoclonal antibodies. AB - Cryostat sections of skin and nerve lesions of leprosy were stained with monoclonal antibodies recognising Mycobacterium leprae antigens and indirect immunofluorescence. In both the tuberculoid and lepromatous lesions, PGL1, 55-65 kDa, 17-kDa protein antigens and cross-reactive non-protein antigens were present. 65-kDa antigens were seen mainly in the skin lesions of lepromatous leprosy. The infiltrates in both the skin and nerve granulomas of tuberculoid and lepromatous leprosy showed membranous staining with monoclonal antibodies recognising PGL1 and 55-65-kDa antigens. Bacilli in the lesions and the cells in the lymph node granulomas of patients with tuberculosis or the infiltrates in the lesions of tinea corporis or sections of normal skin did not show any staining with these monoclonal antibodies. These results confirm that M. leprae antigens are present and are expressed on the infiltrating cells of leprosy lesions. PMID- 2200753 TI - Characterization of a new model of human prostatic cancer: the multicellular tumor spheroid. AB - Multicellular tumor spheroids (MTS) provide a closer in vitro correlate to in vivo malignancy than do conventional monolayer cultures; while simulating many parameters of in vivo growth, MTS systems provide those perquisites (i.e., experimental control, economy, expediency) associated with in vitro evaluation of preclinical therapeutic strategies. For these reasons, we exploited the proclivity of the highly metastatic human prostatic carcinoma subline I-LN-PC3-IA to spontaneously assume a spheroid morphology under routine culture conditions. I LN spheroids demonstrate salient features described in other spheroid systems and exhibit histologic characteristics of human prostate carcinoma. Cells encompassed in the I-LN spheroid format demonstrated functional divergence from their monolayer counterparts with respect to immunoreactivity for prostatic acid phosphatase, positional dependence of prostate-restricted p40 antigen expression, and chemotherapeutic drug response. This new in vitro-in vivo transition model of human prostatic carcinoma should provide a valuable in vitro context to expediently evaluate in vivo correlates of oncolytic protocols on a malignancy that remains refractive to therapy. PMID- 2200755 TI - Coincident implantation, growth and interaction sites within the liver of cancer and reactive hematopoietic cells. AB - We have examined the anatomical-functional sites within mouse liver where phenylhydrazine (PHZ)-induced hematopoietic foci, and M5076 reticulum cell sarcoma, B16F10 melanoma and Lewis lung-carcinoma cells specifically develop as colonies after intrasplenic injection. Cancer foci occurred predominantly in the 2.4 to 4.0 segment of the sinusoidal pathway, corresponding to hepatic acinar zone I. No significant differences were detected between different types of tumor, including their different tendencies to spontaneously metastasize liver, or as a result of the different procedures used for obtaining foci or metastases. In addition, PHZ-treatment of mice previously injected with tumor cells, resulted in double colonization of the liver tissue by both hematopoietic and cancer cells, predominantly in zone I. This spatial coincidence indicates that non cancer-specific mechanisms operate in zone I, either promoting implantation and/or growth of cell colonies or, alternatively, inhibiting these processes in the region surrounding the central vein (Rappaport zone 3). Our observations failed to reveal mutual displacement of cancer or hematopoietic foci by potential competition for development sites in zone I. Enumeration and diameter measurements of cancer foci in PHZ-treated animals showed that the presence of hepatic hematopoietic foci coincided with a significant increase in the hepatic metastasis volume. However, the fact that no significant differences in pulmonary metastases occurred in both the PHZ-treated and control mice given tail-vein injection of cancer cells, and that PHZ reduces cancer cell proliferation in vitro, reveal evidence of local interactions with hematopoietic foci which promote growth of cancer foci in liver. PMID- 2200757 TI - Industrial risk factors for colorectal cancer. AB - Colorectal cancer is the second most common malignancy in the United States, and its incidence rates have sharply increased recently, especially in males. Industrial exposures, both occupational and environmental, are important colorectal cancer risk factors that are generally unrecognized by clinicians. Migration studies have documented that colorectal cancer is strongly associated with environmental risk factors. The causal role of occupational exposures is evidenced by a substantial literature associating specific work practices with increased colorectal cancer risks. Industrially related environmental exposures, including polluted drinking water and ionizing radiation, have also been associated with excess risks. Currently, there is a tendency to attribute colorectal cancer, largely or exclusively, to dietary and other lifestyle factors, thus neglecting these industrially related effects. Concerted efforts are needed to recognize the causal role of industrial risk factors and to encourage government and industry to reduce carcinogenic exposures. Furthermore, cost-effective screening programs for high-risk population groups are critically needed to further reduce deaths from colorectal cancer. PMID- 2200754 TI - Immunofluorescence study of the action of navelbine, vincristine and vinblastine on mitotic and axonal microtubules. AB - Among the various non-naturally-occurring Vinca alkaloid compounds, nor-anhydro vinblastine (Navelbine, NVB) exhibits in preliminary clinical studies broader anti-tumor activity and lower neurotoxicity than vinblastine (VBL) and vincristine (VCR). The action of these 3 Vinca alkaloids on axonal and mitotic microtubules has been studied experimentally in a specific model, the tectal plate anlage of mouse embryos at the earliest stages of neuronal differentiation. Post-implantation embryos were cultured in toto in a medium containing increasing concentrations of drugs. Microtubules were stained using immunofluorescence with a tubulin-specific polyclonal antibody in semi-thin sections after embedding in high-molecular-weight polyethylene glycol. All drugs induced depolymerization of mitotic interpolar microtubules and cell metaphase block at the same concentration. Increasing the concentrations led to progressive depolymerization of kinetochore microtubules. However, NVB was the only drug to induce complete microtubule depolymerization. The activity of the 3 compounds on axonal microtubules was identical: depolymerization of a labile pool of microtubules. This was observed at higher concentrations with NVB than with the 2 other Vinca alkaloids. Our results show that, in this model, NVB is as active on mitotic microtubules as VCR and VBL, and less active on axonal microtubules. None of the 3 drugs modified microtubule length but all appeared to induce disruption of the labile microtubule pool without altering the stable pool. PMID- 2200756 TI - Immunolocalization of phosphoprotein B23 in proliferating and non-proliferating HeLa cells. AB - Localization of protein B23 in HeLa cells under different growth conditions was studied using indirect immunofluorescence. Bright nucleolar fluorescence was observed in exponentially growing cells. After 3 to 4 days, the initial cell inocula entered a phase of stationary growth as defined by no increments in cell number. The nucleolar fluorescence was then diminished and a general nuclear immunofluorescence was observed. This change in localization of fluorescence indicated that protein B23 had migrated out of the nucleoli during the suboptimal growth conditions. Relocation of protein B23 in nucleoli was observed in cells of stationary growth after treatment with adriamycin or daunomycin at their subtoxic concentrations (10(-10) M). Adriamycin and daunomycin, at their toxic concentrations (greater than 5.0 x 10(-7) M), on the other hand, inhibited cell growth and induced B23 translocation from nucleoli to nucleoplasm in growing cells. These results indicate that both adriamycin and daunomycin exhibit biphasic effects on the proliferation of cells by either stimulation or inhibition depending on the drug concentrations and the growth conditions. B23 translocation, as observed by immunofluorescence may be a simple and rapid method for assessing inhibition-stimulation growth response to anti-tumor therapy. PMID- 2200758 TI - Evaluation of carboplatin (NSC 241240) in patients with recurrent or metastatic renal cell carcinoma. AB - Eighteen evaluable patients with metastatic or recurrent renal cell carcinoma were treated with carboplatin. Fourteen patients received 400 mg/m2 as the initial dose, and four patients received reduced doses based on prior radiation therapy and/or elevated serum creatinine. No responses were seen. Median survival of these 18 patients was 8.3 months. Risk group status which previously has been identified as an important indicator of survival was predictive for survival in this study. Patients in the most favorable risk groups had a median survival of 21.2 months vs. 6.6 months for the most unfavorable risk groups. No lethal toxicities occurred with the administration of carboplatin; however, 66% of patients received doses of sufficient magnitude to cause severe or life threatening thrombocytopenia or anemia. PMID- 2200759 TI - Clinical toxicity associated with tiazofurin. AB - Tiazofurin, an investigational antimetabolite, is undergoing clinical evaluation in leukemia. We analyzed the data base of 198 patients entered in Phase I trials to characterize the incidence and severity of toxicities associated with tiazofurin according to dose and schedule. Severe myelosuppression occurred infrequently, and was not dose-dependent. A five day bolus schedule had a higher incidence of severe or life-threatening neutropenia than other schedules. Tiazofurin produced lymphopenia which was not dose-dependent in the range of 23 36% decrease from baseline, and the effect on lymphocyte count was generally greater than the decline in neutrophil count. Non-hematologic toxicity of a moderate or worse severity (greater than or equal to grade 2) included nausea and vomiting (18% of all courses), serum transaminase elevations (SGOT, 16%; SGPT, 9%), rash (9%), stomatitis (3%), conjunctivitis (3%), headache (10%), other signs of central nervous system toxicity (8%), and cardiac toxicity, primarily pleuropericarditis (4%). Dose-related cutaneous toxicity, headache, and nausea and vomiting were evident in the five day bolus schedule, and myalgia was more frequently reported at higher doses on the single dose schedule. The five day continuous infusion (CI) schedule had a higher incidence of neurotoxicity, cardiac toxicity, SGPT elevations and ocular toxicity than the daily for five days bolus schedule, but none of these differences attained statistical significance. Although the peak plasma concentrations of tiazofurin achieved with the five day bolus schedule were 3-fold higher than the steady-state plasma levels seen with an equal dose given by CI, the area under the concentration-time curve (AUC) was approximately 1.6-fold higher with CI. These observations suggest that both high peak plasma concentrations (above 400 microM) and prolonged exposure to plasma levels exceeding 50 microM may result in a higher incidence of serious non-hematologic toxicity. PMID- 2200760 TI - Beta-thalassemia in Turkey. AB - A review is presented of the various beta-thalassemia alleles observed in nearly 191 patients with beta-thalassemia major and their 182 heterozygous relatives. Determination was by gene amplification and dot-blot hybridization with synthetic probes, specific for 27 different mutations. Eighteen mutations have been observed; six of these account for nearly 83% of all thalassemia abnormalities. A new mutation, i.e. a G----C mutation at the acceptor splice site of IVS-I, was found in one teenager who was homozygous for this disease. The high consanguinity among the families was considered the main reason for the high number of patients with a homozygosity for the IVS-I-110 (G----A) mutation. Combinations of different mutations were present in many patients; some were mildly affected because of the specific mutation present on one chromosome. Combinations of classical beta-thalassemia and an abnormal hemoglobin mainly concerned Hb S. Hbs Knossos and Lepore were rare occurrences. A comparison of hematological data for adults with heterozygosities for some of the common alleles confirmed the low Hb A2 values in IVS-I-6 (T----C) heterozygotes and the high Hb F values for codon 8 (-AA), IVS-II-1 (G----A), and IVS-I-1 (G----A) heterozygotes. PMID- 2200761 TI - Beta-thalassemia in Yugoslavia. AB - This study concerned the evaluation of beta-thalassemia alleles in nearly 50 patients with beta-thalassemia major and in 130 -thalassemia heterozygotes using gene amplification and dot-blot hybridization with synthetic probes. Fourteen different mutations were observed; of these, three (IVS-I-110; IVS-I-6; IVS-I-1) account for some 75% of all beta-thalassemia alleles. Newly discovered variants, i.e. T----C in the initiation codon and AATAAA----AATGAA in the poly A site were observed in a few patients. The poly A mutation with classical beta-thalassemia alleles result in thalassemia intermedia. Hb Lepore is a rather common abnormality and combinations of this variant with beta-thalassemia often result in severe disease; a search for beta-thalassemia mutations among patients affected with this disease should include an analysis to detect this hemoglobin abnormality. PMID- 2200762 TI - Beta-thalassemia in Bulgaria. AB - Analyses of DNA from 64 patients with thalassemia major using the hybridization technique of amplified DNA with radiolabeled synthetic oligonucleotide probes identified 13 different beta-thalassemia mutations. The codon 39 (C----T) and IVS I-110 (G----A) mutations occurred most frequently but seven additional mutations were observed which were present at frequencies of 3.9 to 10.2%. This broad spectrum of beta-thalassemia alleles complicates the analyses for institutions involved in prenatal diagnosis. Promoter mutations were rare and the frequencies of two other mild mutations [IVS-I-6 (T----C) and the poly A mutation] were relatively low indicating that beta-thalassemia is a severe disease among Bulgarians. The high frequencies of 4.7-5.5% for the four frameshifts at codons 5, 6, 8, and 8/9 may be specific for this population. PMID- 2200763 TI - Obstructive nephrolithiasis and ureterolithiasis associated with chronic renal failure in horses: eight cases (1981-1987). AB - Eight adult horses with obstructive nephrolithiasis and/or ureterolithiasis were examined between 1981 and 1987. One horse had bilateral ureteral obstruction at hospital admission; the others had unilateral ureteral obstruction. All horses had similar bilateral renal pathologic findings that were compatible with chronic intermittent or complete obstruction. Horses were referred for evaluation of weight loss, poor performance, and/or decreased appetite. Clinical findings, laboratory results, and/or postmortem findings in all horses supported the diagnosis of chronic renal failure. Age of the 8 horses varied between 2 and 17 years; 5 of the 8 were between 2 and 3 years old. Seven horses were Thoroughbreds and 1 was a Standardbred. Of the horses examined, 4 were females and 4 were males (2 geldings). Diagnosis of obstructive nephrolithiasis and/or ureterolithiasis was made in all of the hospitalized horses based on examination per rectum and/or renal ultrasonographic findings. Surgical removal of the obstructing calculi was performed in one horse. Although etiopathogenesis could not be proven, histopathologic findings in the kidneys of the horses of our study were suggestive of renal failure secondary to obstructive urinary disease. PMID- 2200764 TI - Economic relevance, diagnosis, and countermeasures for degenerative joint disease (osteoarthrosis) and dyschondroplasia (osteochondrosis) in pigs. PMID- 2200765 TI - What is your diagnosis? Generalized enlargement of the kidneys with ventral displacement of abdominal viscera. PMID- 2200766 TI - The distribution of lymphatic stomata in the diaphragm of the golden hamster. AB - Golden hamster diaphragms were observed with both light and electron microscopes to examine the distribution of lymphatic stomata and their morphological features. Lymphatic stomata were present on the inferior surface but absent on the superior surface. This observation was also supported by the results of India ink injection into the peritoneal and pleural cavities. On the inferior surface of the diaphragm, lymphatic stomata tended to form radial rows running from the centre to the periphery; i.e. they were found throughout the muscular and tendinous portions, although the density of their distribution was higher in the latter. Lymphatics and lymphatic lacunae in the tendinous portion were generally smaller than those in the muscular portion. Lymphatic flow into the lymphatics of the tendinous portion seems to be slow, suggesting that lymphatic stomata in the portion may be a functionally inactive reserve. PMID- 2200767 TI - In memoriam Henricus (Hans) Kuypers, F.R.S., 1925-1989. PMID- 2200768 TI - Femoral anteversion in healthy children. Application of a new method using ultrasound. AB - Femoral anteversion (torsion) was measured in 219 healthy children aged 1-15 years (boys 128, girls 91). The hips and knees were examined using a standard static-image B-mode compound scanner. The torsion in each femur was calculated. The findings show: (1) A significant negative correlation between femoral anteversion and age (r = -0.43), with only 8-22% being accounted for by age (r2 value). (2) A significant correlation between anteversion of the two femora (r = 0.77). (3) No sex difference for femoral anteversion and its asymmetry. (4) Marked degrees of femoral anteversion asymmetry (more than 10 degrees) show a pattern suggesting a relation to age, side and possibly sex. (5) Abnormal femoral anteversion asymmetry in 12 children, there being an excess of children with orthopaedic symptoms and signs in the group with femoral anteversion outside 2 S.D. (6) A relation between anteversion asymmetry and foot length/tibial length ratio. (7) No relation of femoral anteversion to social class, order in family, parental age at birth of child, birth weight and presentation. (8) A significant correlation of femoral anteversion between siblings (r = 0.66). PMID- 2200769 TI - Fractionator studies on Purkinje cells in the human cerebellum: numbers in right and left halves of male and female brains. AB - Direct estimates of the numbers of Purkinje cell nucleoli in 22 aged human cerebella of known weight were obtained from paraffin-embedded sections using the fractionator. The nucleoli were counted in single sections. The estimates are unbiased by fixation, section thickness or sampling errors and are free from any assumptions about shape, size or spatial orientation. Left and right sides of the cerebellum were analysed in ten subjects whilst sex differences were examined in eleven subjects. No significant lateral differences in fixed weight or nucleolar number were observed. The group means (coefficients of variation) per side were 45 g (18%) and 7.8 millions (26%) respectively. The average complement of nucleoli in 22 cerebella amounted to 15.6 millions (22%). Estimated numbers did not show any significant correlation with cerebellar weights and, in a subsample of these brains (five male and six female), apparent sex differences were not significant. PMID- 2200770 TI - Seminal alpha-glucosidase activity as a marker of epididymal pathology in nonazoospermic men consulting for infertility. AB - Glucosidase (alpha G) activity was measured in sperm free seminal plasma from 1200 patients consulting for primary infertility, in whom clinical examination of epididymides revealed some abnormalities and histories of genital infections. They constituted the group with epididymal pathology (P) that was compared with a reference group (R) of 246 men without any epididymal pathology. The distribution of alpha G was significantly different between the two groups, even if we considered only the subjects in group P with normal sperm count (PN: 353 men: p less than 10(-6). 15.9% of subjects in group PN exhibited alpha G values as low as vasectomized men, versus 1.2% in group R. A linear relationship was established between alpha G and sperm content in both groups, but alpha G activities were systematically lower in group P (y = 0.19 x + 64) than in group R (y = 0.30 x + 86). There was no correlation between alpha G and the percent of sperm motility. On the contrary, we found statistically more clinical epididymal abnormalities in cases of decreased alpha G activity than in cases of normal alpha G activity (p less than .01). PMID- 2200771 TI - Effect of egg yolk medium on the acrosome reaction of human spermatozoa. AB - Preincubation of human spermatozoa in an egg yolk medium (TESTY) at 5 C, followed by washing at 37 C by centrifugation and resuspension in a standard medium (BWW), enhanced the percentage of spermatozoa that underwent the acrosome reaction and increased sperm penetration into zona-free hamster oocytes, as compared with BWW treatment only. The difference in the occurrence of the acrosome reaction between the two treatment protocols was present whether the spermatozoa were incubated for 3 or for 18 h. The increase in acrosome reaction occurred only when spermatozoa were washed after TESTY treatment. Washing at 5 C was not as effective as washing at 37 C. No increased loss of acrosomes was observed when BWW-treated spermatozoa were subjected to the washing procedure. Ionophore A23187 stimulated the acrosome reaction of BWW-treated but not of TESTY-treated spermatozoa, whether or not they were washed before ionophore treatment. In the absence of egg yolk, the medium (TEST) caused only a small enhancement in the acrosome reaction as compared with BWW, but an increase occurred upon addition of ionophore A23187. We conclude that treatment with TESTY enhances the capacitation/acrosome reaction of human spermatozoa and that the removal of egg yolk after incubation, as well as the temperature shock, contribute to this effect. PMID- 2200772 TI - Negative feedback regulation of pulsatile LH secretion during treatment with an LHRH antagonist in rams. AB - Suppression of LH and testosterone secretion in sexually active rams by the short term administration of an LHRH antagonist results in a compensatory increase in the release of LHRH from the hypothalamus. This is inferred from the observed increase in the frequency of LH pulses in peripheral blood during the period of recovery when the pituitary regains its responsiveness to LHRH. To investigate the nature of the inhibitory feedback signal which triggers this compensatory response, a single intravenous injection of 1 mg of an LHRH antagonist (28 micrograms/kg; N-Ac-D-pCl-Phe 1, D-pCl-Phe 2, D-Trp 3, D-hArg (Et 2) 6, D-Ala 10, LHRH) was given to groups of intact, testosterone-implanted castrated and castrated rams housed under stimulatory short days. Pulsatile LH secretion was monitored in blood samples collected every 10 min for 34 h. The treatment caused an immediate blockade of LH pulses in all three groups of rams followed by a progressive recovery of LH secretion from 12-30 h. Compared to the pretreatment period, intact rams showed a significant increase in frequency of LH pulses during the recovery period. Castrated rams did not show this increase, with or without supplementary testosterone. Since the circulating testosterone concentration decreased after the blockage of LH secretion in the intact rams, but not in the castrated or testosterone-implanted castrated rams, we conclude that it is the reduction in the steroid negative feedback signal which leads to a compensatory increase in the activity of the LH pulse generator. PMID- 2200773 TI - Plasma growth hormone and insulin concentrations in double-muscled and normal bull calves. AB - Blood samples were taken from 19 double-muscled (DM) and 20 normal (N) bull calves at the ages of 1.5, 2, 2.5, 3, 3.5, 4, 5.5, 6.5 and 9 mo to compare the plasma concentrations of growth hormone and insulin in DM with those in N bull calves and to relate these to differences in growth rate between the two breed groups. Double-muscled bull calves were lighter (P less than .0001) than N calves at all ages and had lower (P less than .001) preweaning and postweaning rates of gain. Double-muscled bull calves had lower (P less than .01) mean growth hormone concentration than N calves. Mean growth hormone concentration was correlated positively with body weight and preweaning rate of gain. The effect of age on growth hormone concentration was linear (P less than .05); however, mean growth hormone concentration fluctuated between ages 1.5 to 4.5 mo but stabilized after 5.5 mo of age in both breed groups. Mean insulin concentration was lower (P less than .01) in DM than in N bull calves. The effect of age on insulin concentration was both linear and quadratic (P less than .0001). Mean insulin concentration generally was constant in both breed groups, at around .75 ng/ml, from 1.5 to 6.5 mo of age but rose sharply to around 1.67 ng/ml after weaning when the bulls were put on a high-energy diet. PMID- 2200774 TI - Portal blood flow in beef steers: comparison of techniques and relation to hepatic blood flow, cardiac output and oxygen uptake. AB - We compared two techniques for measuring blood flow through portal-drained viscera (PDV) of beef steers and measured portions of cardiac output and total oxygen uptake attributable to PDV and hepatic tissues. Four steers (198 +/- 2 kg), equipped with chronic catheters in appropriate vessels, a transit-time ultrasound probe around the hepatic portal vein and a temporary cardiac output thermodilution catheter, were fed a 60:40 hay: concentrate diet. Treatments, designed to alter blood flow, were: 12 equal meals every 2 h (CNTL); CNTL plus 2 mg clenbuterol in one meal (CLEN); and a 65-h fast (FAST). Blood flow through PDV was measured by dilution of p-aminohippurate (PAH) and transit-time ultrasound. Hepatic blood flow was measured by PAH dilution and cardiac output was measured by thermodilution. Blood flow measured by transit-time ultrasound was consistently slower (45%, P less than .01) than blood flow measured by PAH dilution. Necropsy revealed anatomical constraints that precluded proper placement and function of the flow probes. Cardiac output (liters/h) was greater (P less than .05) for CLEN (3,082) than for CNTL (1,655) or FAST (1,047). Percentage of cardiac output flowing through PDV and hepatic tissues was less (P less than .05) for CLEN (23 and 24%) than for CNTL (31 and 38%) or FAST (32 and 38%). Whole body oxygen uptake (mmol/h) was greatest (P less than .05) for CLEN (4,220), intermediate for CNTL (2,999) and least for FAST (1,965). Percentage of oxygen uptake attributable to hepatic tissues was greater (P less than .05) for FAST (31%) than for CLEN (18%), with CNTL intermediate (24%). Percentage of oxygen uptake attributable to PDV (22%) was not affected (P greater than .05) by treatments. PMID- 2200775 TI - Subclinical ammonia toxicity in steers: effects on hepatic and portal-drained visceral flux of metabolites and regulatory hormones. AB - Four calves (avg wt 161 kg) were surgically fitted with indwelling catheters in the femoral artery and femoral, portal, hepatic and mesenteric veins to study the effects of subclinical ammonia toxicity on portal-drained viscera (PDV) and hepatic (HEP) net flux of key metabolites and pancreatic hormones. Hyperammonemia was induced via administration of ammonium chloride (NH4Cl; 12 mumol.kg BW-1.min 1) via the femoral vein catheter for 240 min; infusions were preceded (PRE) and followed (POST) by 60- and 180-min control periods, respectively. Blood samples were obtained from the arterial catheters, and portal and hepatic vein catheters. Net flux rates were calculated by multiplying venoarterial differences by blood flow. Arterial plasma ammonia N peaked (P less than .01) at 327 micrograms/dl; hepatic ammonia extraction increased (P less than .01) from 10 to 23% during NH4Cl infusion. Arterial plasma glucose concentrations increased (P less than .05) during NH4Cl infusion (90.5 vs 82.6 mg/dl) concomitant with trends toward a reduction in net HEP glucose output. Portal-drained visceral release of insulin did not increase (P greater than .10) during NH4Cl infusion despite the steady rise in circulating glucose concentration; however, cessation of NH4Cl infusion resulted in a 109% increase (P less than .05) in PDV insulin release at +60 min POST. Plasma L-lactate, nonesterified fatty acids, urea N and glucagon concentrations and net fluxes were variable throughout the experiment. Results tend to indicate that hyperammonemia reduced hepatic glucose output and glucose mediated pancreatic insulin release. PMID- 2200776 TI - George H. Hart, 1883-1959: a brief biography. PMID- 2200777 TI - Growth and carcass characteristics and serum growth hormone, prolactin and insulin profiles in Debouillet lambs treated with ovine growth hormone and(or) zeranol. AB - Sixteen Debouillet wether lambs (approximately 3 mo old) were placed indoors in 1.5- x 3-m pens (14 h light:10 h dark) 28 d after weaning. Lambs received no implant or a 12-mg zeranol implant on d-2 (eight lambs/group). Two days later (d 0), animals received either 0 or 2.5 mg ovine growth hormone (oGH, eight lambs/group) s.c. on alternate days for 42 d. Animals had ad libitum access to water, salt, mineral and a pelleted alfalfa diet (16% CP). After 42 d, lambs were slaughtered to evaluate carcass traits, organ weights and femur characteristics. Zeranol by oGH interactions were not detected (P greater than .20). Zeranol increased (P less than .05) BW, improved (P less than .05) feed:gain during the first 20 d and increased (P less than .10) feed intake during the last 22 d of the 42-d trial compared with controls. Carcass characteristics were not altered (P greater than .10) by 12 mg zeranol. Serum insulin and prolactin were elevated (P less than .05), but serum GH was not influenced by zeranol compared with controls. Exogenous oGH decreased feed intake (P less than .10) and improved feed:gain (P less than .05) during the initial 20 d compared with controls, but did not influence (P greater than .20) these variables during the last 22 d of the study. Carcass traits were not influenced (P greater than .10) by oGH. Exogenous ovine GH dramatically elevated (P less than .05) serum GH, but did not affect serum insulin or prolactin (P greater than .10).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2200778 TI - Effect of endothelin-1 on pulmonary resistance in rats. AB - We examined the effect of endothelin-1 (ET-1), a novel 21-residue vasoconstrictor peptide, on pulmonary resistance (RL) in Wistar rats. The lung volume, tracheal flow, and transpulmonary pressure of tracheotomized and paralyzed rats were measured with a fluid-filled esophageal catheter and a pressure-sensitive body plethysmograph. RL was calculated by the method of von Neergaard. The femoral artery was cannulated to measure the mean arterial blood pressure. Intravenous bolus administration of synthetic ET-1 provoked a dose-dependent increase in RL in rats. The bronchoconstricting effect reached maximum at 500 pmol/kg. This bronchoconstriction was observed in less than 5 min, increased up to 15 min, and was sustained for 60 min. ET-1 increased the mean arterial blood pressure in a dose-dependent manner. We conclude that ET-1 is a hitherto unknown potent bronchoconstrictor that has a sustained effect in vivo. The potential physiological and pathophysiological role of this new peptide in the development of respiratory disease warrants further investigation. PMID- 2200779 TI - Effect of serotonin on expiratory pulmonary resistance in cats. AB - In five anesthetized paralyzed cats, mechanically ventilated with tidal volumes of 36-48 ml, the isovolume pressure-flow (IVPF) relationships of the lung were studied under control conditions and during serotonin-induced bronchoconstriction. At the end of a tidal inspiration, airway opening pressure was set between +3 and -15 cmH2O for single tidal expirations. After control measurements, animals were treated with progressively increasing doses of intravenous serotonin (10, 20, 50, and 100 micrograms.kg-1.min-1) and all measurements were repeated at each dose. No animal became flow limited during passive expiration against atmospheric pressure. Disregarding flow-limited segments, IVPF plots for three lung volumes showed that the resistive pressure flow relationships were curvilinear under all conditions, thus fitting Rohrer's equation. Under control conditions and during the lowest dose of serotonin, the volume dependence of pulmonary resistance (RL) tended to balance its flow dependence so that during lung deflation against atmospheric pressure RL remained nearly constant. However, as bronchoconstriction became more pronounced, RL often increased disproportionately at the lower lung volumes. Changes in expiratory RL with serotonin relative to control values varied according to the flow rates used to make comparisons. The technique used to determine RL will partly determine the results obtained. PMID- 2200780 TI - Electrical stimulation alters fatty acid metabolism in isolated skeletal muscle. AB - Little is known about the contribution of plasma free fatty acid (FFA) and intramuscular triacylglycerol (TG) as substrates for energy production during prolonged electrical stimulation of skeletal muscle. The purpose of this study was to investigate the effects of continuous and intermittent electrical stimulation protocols of different intensities on exogenous FFA oxidation, exogenous FFA incorporation into intracellular TG, and intracellular TG content in the isolated in vitro rat flexor digitorum brevis muscle preparation. Muscles were electrically stimulated for 0.5 h continuously at 0.2 Hz or intermittently (30 s on, 60 s off) at 0.2, 0.4, 0.8, and 5.0 Hz while incubated at 37 degrees C in 0.5 mM palmitate-3% bovine serum albumin medium (pH 7.4) in the presence of insulin (100 microU/ml) and glucose (11 mM). Control muscles were frozen immediately after excision or incubated for 0.5 h. At similar frequencies, less exogenous FFA esterification and more exogenous FFA oxidation occurred during continuous than during intermittent stimulation. As the frequency of intermittent stimulation increased, the amount of exogenous FFA esterified decreased and the amount of exogenous FFA oxidized increased. The data also indicate that at least a portion of TG was constantly being hydrolyzed during electrical stimulation. Under stimulation conditions in which exogenous FFA esterification was below the control (resting muscle) level, intramuscular TG content was significantly decreased compared with control TG content values. Thus both plasma FFA and intramuscular TG are substrates for energy production during electrical stimulation. However, the stimulation parameters employed affect the quantities utilized. PMID- 2200781 TI - Simulation of the effects of mechanical nonhomogeneities on expiratory flow from human lungs. AB - A computational model for expiration from lungs with mechanical nonhomogeneities was used to investigate the effect of such nonhomogeneities on the distribution of expiratory flow and the development of alveolar pressure differences between regions. The nonhomogeneities used were a modest constriction of the peripheral airways and a 50% difference in compliance between regions. The model contains only two mechanically different regions but allows these to be as grossly distributed as left lung-right lung or to be distributed as a set of identical pairs of parallel nonhomogeneous regions with flows from each merging in a specified bronchial generation. The site of flow merging had no effect on the flow-volume curve but had a significant effect on the development of alveolar pressure differences (delta PA). With the peripheral constriction, greater values of delta PA developed when flows were merged peripherally rather than centrally. The opposite was true in the case of a compliance nonhomogeneity. The delta PA values were smaller at submaximal flows. Plots of delta PA vs. lung volume were similar to those obtained experimentally. These results were interpreted in terms of the expression used for the fluid mechanics of the merging flows. delta PA was greater when the viscosity of the expired gas was increased or when its density was reduced. Partial forced expirations were shown to indicate the presence of mechanical nonhomogeneity. PMID- 2200782 TI - Measurement of peptidoleukotrienes in biological fluids. AB - Samples of human bronchoalveolar lavage fluid (BALF) and urine were utilized to demonstrate methods for quantitation and validation of leukotrienes (LTs). These methods utilize an enzyme immunoassay (EIA) that uses commercially available reagents, the antibody recognizing LTC4, LTD4, LTE4, and N-acetyl LTE4. BALF containing epithelial lining fluid was collected from atopic asthmatics both before and 5 min after the subjects had been challenged with a local instillation of allergen into the airways. BALF samples collected without allergen challenge had low levels of immunoreactive LTs, whereas samples collected after allergen were markedly elevated. After high-performance liquid chromatography (HPLC) separation of LTs, EIA revealed the presence of LTC4. The identity was validated by incubating LTC4 with a bovine gamma-glutamyl transpeptidase with dipeptidase activity that converted added [3H]-LTC4 as well as LTC4 immunoreactivity to LTE4. Urine samples collected from six healthy volunteers, one patient with adult respiratory distress syndrome (ARDS), and three patients in status asthmaticus were also analyzed for LTs. After HPLC separation of LTs and quantitation by EIA, urine samples from healthy subjects were found to have low but measurable LTE4. In contrast, the urine samples from the patients in status asthmaticus and from the ARDS patient had large elevations of LTE4 levels compared with healthy subjects. When the HPLC fractions containing [3H]LTE4 and LT immunoreactivity in the ARDS sample were treated with acetic anhydride, HPLC analysis indicated that both radiolabel and immunoreactivity now eluted at the retention time of N-acetyl LTE4, the derivatized product of LTE4. The methods described are relatively easy and can be used to measure and validate the existence of peptidoleukotrienes in biological samples. PMID- 2200783 TI - Ultrasonographic localization for renal biopsy. AB - One hundred and fifty consecutive percutaneous renal biopsies were performed using ultrasonography to localise the site and depth of the lower pole of the left kidney. Renal tissue was obtained in 95% of cases and an accurate histopathological diagnosis was reached in 89% of patients. Gross haematuria following the procedure occurred in 6%, but was usually transient. No other complications were encountered. Ultrasonographic marking of the biopsy site and depth is a quick, simple, accurate and safe method of localizing the kidney for the purpose of a biopsy. PMID- 2200784 TI - Plasma renin activity in shock due to aluminium phosphide poisoning. AB - Plasma renin activity (PRA) was estimated in 30 patients with aluminium phosphide (AIP) poisoning (study group) admitted in shock. Ten patients in shock other than due to AIP poisoning (Group II A) and 20 normal healthy subjects (Group II B) served as controls. The PRA was significantly higher in the study group and group II A as compared to normal healthy subjects (p less than 0.001). Significantly higher PRA was found in the study group as compared to Group II A (p less than 0.001). The initial higher PRA continued to rise further in the study group but it started decreasing in Group II A as the duration of shock advanced. Continuation of shock in AIP poisoning was probably due to slow release of toxic PH3 gas, which was detected by positive silver nitrate paper test. The rise in PRA was directly proportional to the dose of pesticide consumed. There was direct relationship of mortality with increased PRA. Angiotensin converting enzyme inhibitors may have a role in combating shock in AIp poisoning. PMID- 2200785 TI - Progression of chronic renal diseases. Newer concepts. PMID- 2200786 TI - Complete heart block in rheumatoid arthritis. AB - A case of rheumatoid arthritis with complete AV heart block is reported. The relevant literature is briefly reviewed. PMID- 2200787 TI - Candida albicans and ABO blood groups. PMID- 2200789 TI - Operative treatment of idiopathic scoliosis. PMID- 2200788 TI - Mechanical simulation of shear stress on the walls of peripheral arteries. AB - In the last few years many attempts were made to line artificial vascular grafts with in vitro grown endothelial cell layers and thereby to minimize the risk of thromboembolism. However, adherence and resistance against shear stress forces were not tested under physiological pulsatile shear stress forces. In this paper, a mock-circulation apparatus is described, which simulates various forms of pulsatile shear stress, and which at the same time meets the requirements of cell cultivation. It can be sterilized and needs less than 700 ml of culture medium for priming. The generated flow profile can be adapted to a wide range of shear stress and also to different viscosities of used media. To take account of the different viscosities of culture medium and blood, a computerized calculation of the shear stress pattern was performed. Using the results of this computer model, the flow pattern was modified to obtain normal physiological shear stress when using culture medium. Results of pulse generation and simulation for the superficial femoral artery are presented. PMID- 2200790 TI - B-mode ultrasound scanning in the detection of proximal venous thrombosis after total hip replacement. AB - A prospective study of the accuracy of real-time B-mode ultrasonography in detecting deep venous thrombosis in the femoral and popliteal veins of the lower extremity was conducted on a consecutive series of patients who had had a total hip replacement. Ascending venography was used as a diagnostic standard. One hundred and forty-three patients had ultrasound studies of both lower extremities and a venographic study of the operatively treated lower extremity at an average of 7.6 days postoperatively. The two tests were done within twenty-four hours of each other. Both ultrasonography and venography were done on 152 extremities. Two paired studies were excluded from the analysis of results because the ultrasound scans could not be interpreted. In 131 extremities, both diagnostic tests were negative for proximal thrombosis. Eight extremities had isolated thrombosis of a vein in the calf that was detected only by venography. In nineteen extremities, old or fresh thrombosis was diagnosed by venography. In four extremities, an old thrombosis of the superficial femoral vein was detected by both studies. In four of the extremities that had a new thrombus in the common femoral vein and in nine that had a new thrombus in the superficial femoral vein, abnormal findings on ultrasound scans correlated with those on venograms. There were two false negative ultrasound scans and one false-negative venogram. The sensitivity, specificity, and accuracy of ultrasonography were 89, 100, and 99 per cent for the diagnosis of thrombosis of the proximal veins of the lower limb and 63, 100, and 93 per cent for the diagnosis of thrombosis when the entire venous system of the limb was included.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2200791 TI - What makes microtubules dynamic? PMID- 2200792 TI - A 116,000 Mr nucleolar antigen specific for the dense fibrillar component of the nucleoli. AB - In ATT, a human autoimmune serum, we found anti-nucleolar antibodies that recognized nucleolar antigens confined to a single nucleolar compartment, the dense fibrillar component (DFC). We localized these antigens by immunoelectron microscopy in DFC of HeLa cell nucleoli both on Lowicryl sections and cryoultrathin sections without embedding. The antigens were solubilized by incubation with 2M NaCl but not by RNase or DNase treatment. The ATT serum crossreacted with rat liver nucleoli and PtK1 cell nucleoli in which immunofluorescence labelling displayed a clumpy pattern. During mitosis, the antigens dispersed in the cytoplasm until late telophase, when they gathered in the prenucleolar bodies. In human peripheral lymphocytes, or HeLa cells treated with actinomycin D, the antigens were still present but the fluorescence intensity decreased. By immunoblotting using human nuclear extracts, the ATT serum bound to a 116,000 Mr protein at dilutions up to 1:2000. The reactivity of this band diminished with actinomycin D-treated nuclear extracts. Two minor bands were also observed at 97 and 70K (K = 10(3) Mr). Immunopurification by competition or elution demonstrated that the 116K antigens were at the origin of the nucleolar labelling. This DFC marker appeared to be different from the NOR silver-stained proteins, which in our preparations exhibited apparent molecular weights of 105, 80 and 38-40K. In addition, these 116K antigens did not exhibit the characteristics described for DNA topoisomerase I, fibrillarin or nucleolin. We propose the 116K antigen as a new marker of the DFC of the nucleoli. PMID- 2200793 TI - Polymorphonuclear leukocyte phagocytosis of Capnocytophaga ochracea in three dimensional plasma clots. AB - We have studied the ability of human polymorphonuclear leukocytes (PMN) to phagocytose Capnocytophaga ochracea in three-dimensional fibrin meshworks. Phagocytosis was assessed in three systems: (1) the PMN and bacteria were mixed together with plasma and clotted; 60 +/- 13% phagocytosis occurred after 60 min; (2) PMN were overlaid on clots containing bacteria; the PMN migrated into the clot and after 60 min 52 +/- 7% phagocytosis was seen; (3) PMN had to migrate from within one clot into a second containing bacteria; phagocytosis after 60 min was 54 +/- 3%. In the clots, PMN released lysozyme but this was not significantly enhanced by phagocytosis. These findings indicate that PMN are capable of phagocytosing in each of the three-dimensional systems tested and that they are capable of both migration into and subsequent phagocytosis in a model that more closely mimics the in vivo structure in which PMN would normally perform. PMID- 2200794 TI - Substratum-induced stress fiber assembly in vascular endothelial cells during spreading in vitro. AB - We tested whether aortic endothelial cell (EC)-synthesized substrata, which modulate smooth muscle cell proliferation and EC motility following injury, could influence EC actin cytoskeleton and spreading in vitro. A partial characterization of the substrata indicates that the substratum prepared by deoxycholic acid extraction (DOC-derived substratum) is enriched with fibronectin and type IV collagen. Substratum prepared by removal of the intact monolayer with 20 mM EGTA in PBS (EGTA-derived substratum) contains fibronectin and heparan sulfate proteoglycan, but no type IV collagen. Morphometric analyses were performed on fixed and cytoskeletal antibody treated EC in order to quantitate the extent of spreading and stress fiber (SF) assembly. Compared to plastic, the DOC-derived substratum, a collagenase-treated DOC-derived substratum (CT-DOC derived substratum) and the EGTA-derived substratum promote EC spreading 2.3-, 2.9- and 1.7-fold, respectively. In addition, there are 4.2-, 4.1- and 2.0-fold more SF on DOC-, CT-DOC- and EGTA-derived substrata, respectively, when compared to plastic. Subcellular fractionation and immunoprecipitation of cytoskeletal proteins from metabolically labeled EC were performed prior to electrophoresis and fluorography. The DOC-derived substratum increases immunoprecipitable actin and myosin 3- to 4.5-fold in both fractions compared to the EGTA-derived substratum and plastic. Collagenase treatment of the DOC-derived substratum partially inhibits this increase. Cycloheximide treatment prevents the rise in soluble actin and myosin as well as causing a reduction in SF number by 1/2 on the DOC-derived substratum and 2/3 on CT-DOC-derived substratum. We propose that fibronectin-collagen interactions are, in part, responsible for inducing endothelial synthesis of cytoskeletal proteins required for SF assembly. This substratum-induced actin-cytoskeletal reorganization facilitates EC spreading in vitro. PMID- 2200795 TI - Telomere cloning and mammalian chromosome analysis. AB - Although eucaryotic chromosomes vary in size over five orders of magnitude and are constituents of diverse genetic systems the fundamental features of their telomeres appear to be almost completely conserved. This can be exploited to enable molecular cloning of human telomeres in yeast and suggests that many of the ideas that will arise from studies of telomeres in the experimentally tractable ciliates and yeasts will hold true of mammalian telomeres. The particular value of cloned mammalian telomeres is that they contribute reagents for mapping mammalian chromosomes and that they provide one set of elements for the construction of artificial mammalian chromosomes. PMID- 2200796 TI - Flagellar oscillation: new vibes from beads. PMID- 2200797 TI - Cells of the cellular immune and hemopoietic system of the mouse lack lamins A/C: distinction versus other somatic cells. AB - Almost all somatic cells in adult murine tissues express all three nuclear lamins (A, B, C). Here we demonstrate that cells of the hemopoietic system of the adult mouse are an exception in that they express only lamin B. Thus T and B lymphocytes as well as granulocytes and monocytic cells directly isolated from spleen, thymus, blood or bone marrow do not express lamin A/C but only lamin B. In agreement with this observation the murine hemopoietic cell lines EL4, BW5147, HK22, 70Z/3, SP2/0 and PAI express only lamin B. In immunoblotting experiments used to confirm the immunofluorescence data no lamin A/C expression was detected. However, we noticed that murine lamin B occurs in two isoforms, which can be distinguished immunologically. These results reinforce the idea that a functional nuclear lamina can be formed from lamin B alone. They also pose the question of whether cells lacking lamin A/C are more plastic in their developmental programs than those that express all three lamins. PMID- 2200798 TI - Modulation of type X collagen gene expression by calcium beta-glycerophosphate and levamisole: implications for a possible role for type X collagen in endochondral bone formation. AB - Chondrocytes from the cephalic region of 18-day chick embryo sterna were cultured within type I collagen gels in the presence of increasing concentrations of calcium beta-glycerophosphate (Ca beta GP) (2.5 mM, 5 mM and 10 mM) or 2 mM levamisole. Addition of Ca beta GP produced an increase in type X collagen synthesis and when 10 mM Ca beta GP was used, mineral deposits were observed in the matrix elaborated by the chondrocytes. Measurement of mRNA levels of type II and type X collagen microgram-1 total RNA revealed that the level of alpha 1(II) mRNA decreased whereas the level of alpha 1(X) mRNA remained relatively constant in the presence of Ca beta GP. Thus, Ca beta GP appears to increase type X collagen synthesis by enhancing the rate of collagen type X mRNA translation. In levamisole-treated cultures the synthesis of type X collagen and its deposition within the matrix were inhibited. Measurement of mRNA levels micrograms-1 total RNA revealed that the level of alpha 1(II) mRNA increased whereas the level of alpha 1(X) mRNA was markedly decreased in the presence of levamisole. Consequently, it must be concluded that levamisole inhibits type X collagen synthesis by inhibiting type X collagen gene transcription. These results add support for type X collagen having an important role in the mineralization process and have demonstrated that type X collagen synthesis is probably regulated at the mRNA translational stage during chondrocyte hypertrophy. PMID- 2200800 TI - Capillary gas chromatographic-mass spectrometric analysis of plasma methylphenidate. PMID- 2200799 TI - Ion-pair chromatography of inositol polyphosphates with N-methylimipramine. AB - A novel counter-ion, N-methylimipramine, was synthesized and utilized in the separation of inositol phosphates by ion-pair chromatography. The structural identity of the counter-ion was documented by nuclear magnetic resonance spectroscopy. This counter-ion was capable of resolving inositol phosphates isocratically by reversed-phase high-performance liquid chromatography. Solvent polarity and ionic strength markedly affected the retention of the polyphosphorylated inositides. pH, however, was less significant in its effects. Injection of inositol trisphosphate paired to N-methylimipramine into a mobile phase containing tetrabutylammonium ions demonstrated free exchange of the inositide between the counter-ions. This counter-ion may therefore prove useful in defining empirically the mechanisms of ion-pair chromatography. PMID- 2200801 TI - Titration of human immunodeficiency virus type 1 (HIV-1) and quantitative analysis of virus expression in vitro using liquid RNA-RNA hybridization. AB - An assay is described for titration of human immunodeficiency virus type 1 (HIV 1) and for quantitative analysis of virus expression in vitro. The assay utilizes a liquid RNA-RNA hybridization method coupled with reversible target capture (RTC) on oligo(dT) derivatized magnetic particles. The assay provides a rapid, specific, and sensitive method for quantitation of HIV-1 RNA molecules present either in cells or in viral particles from cell-free culture media. Chronically infected monocytoid U1.1 cells were found to carry 52 pg HIV-1 RNA per 200,000 cells (160 HIV-1 RNA molecules per cell). In contrast, acutely infected CEM and H9 cells carried 3010 and 4370 pg HIV-1 RNA per 200,000 cells (9040 and 13,110 HIV-1 RNA molecules per cell, respectively). No hybridization was observed with uninfected cells or cells infected with HIV-2, HTLV-I, HTLV-II, or EBV. Use of liquid HIV-1 RNA hybridization in association with HIV-1 protein detection methods permits more complete characterization of HIV-1 expression in host cells than either method alone, and also provides a method for standardizing preparations of virus. PMID- 2200802 TI - Plasma high density lipoproteins. Metabolism and relationship to atherogenesis. PMID- 2200803 TI - Elevated expression of transforming growth factor-beta and proteoglycan production in experimental glomerulonephritis. Possible role in expansion of the mesangial extracellular matrix. AB - Glomerular accumulation of extracellular matrix is a prominent feature of progressive glomerulonephritis. Previously, we have shown that transforming growth factor-beta (TGF-beta) is unique among growth factors in regulating the production of the proteoglycans biglycan and decorin by glomerular mesangial cells in vitro. We now provide evidence of an elevated expression of TGF-beta, proteoglycans, and fibronectin in glomerulonephritis induced in rats by injection of anti-thymocyte serum (ATS). Glomeruli were cultured from rat kidneys at 1, 4, 7, 14, and 28 d after ATS administration. Increased proteoglycan synthesis was detected beginning on day 4, which peaked at a 4,900% increase compared with control on day 7, and returned toward control levels by day 28. The increased proteoglycan synthesis by cultured nephritic glomeruli, as well as that of fibronectin, were greatly reduced by addition of antiserum raised against a synthetic peptide from TGF-beta. Conditioned media from ATS glomerular cultures, when added to normal cultured mesangial cells, induced elevated proteoglycan synthesis that also peaked on day 7 and that mimicked the response to added exogenous TGF-beta. The stimulatory activity of the conditioned media was blocked by addition of TGF-beta antiserum. Prior addition of the immunizing peptide to the antiserum abolished the blocking effect. The main induced proteoglycans were identified as biglycan and decorin by immunoprecipitation with antiserum made against synthetic peptides from the proteoglycan core proteins. Glomerular histology showed mesangial matrix expansion in a time course that roughly paralleled both the elevated proteoglycan synthesis by the ATS glomeruli and the ability of the conditioned media from these glomeruli to induce proteoglycan synthesis. At the same time there was an increased expression of TGF-beta mRNA and TGF-beta protein in the glomeruli. These results suggest a central role for TGF-beta in the accumulation of pathological extracellular matrix in glomerulonephritis. PMID- 2200804 TI - Abnormal cardiac function in the streptozotocin-diabetic rat. Changes in active and passive properties of the left ventricle. AB - To provide an integrated assessment of changes in systolic and diastolic function in diabetic rats, we measured conscious hemodynamics and performed ex vivo analysis of left ventricular passive-elastic properties. Rats given streptozotocin (STZ) 65 mg/kg i.v. (n = 14) were compared with untreated age matched controls (n = 15) and rats treated with insulin after administration of STZ (n = 11). After 7 d, diabetic rats exhibited decreases in heart rate and peak developed left ventricular (LV) pressure during aortic occlusion. After 26 d of diabetes there were significant decreases in resting LV systolic pressure, developed pressure, and maximal +dP/dt, whereas LV end-diastolic pressure increased and the time constant of LV relaxation was prolonged. The passive LV pressure-volume relationship was progressively shifted away from the pressure axis, and the overall chamber stiffness constant was decreased. However, "operating chamber stiffness" calculated at end-diastolic pressure was increased at 7 d, and unchanged at 26 d. LV cavity/wall volume and end-diastolic volume were increased after 26 d of diabetes. Myocardial stiffness was unchanged at both time intervals. All of the above abnormalities were reversed by the administration of insulin. We conclude that the hemodynamic and passive-elastic changes that occur in diabetic rats represent an early dilated cardiomyopathy which is reversible with insulin. PMID- 2200805 TI - Failure of substrate-induced gluconeogenesis to increase overall glucose appearance in normal humans. Demonstration of hepatic autoregulation without a change in plasma glucose concentration. AB - It has been proposed that increased supply of gluconeogenic precursors may be largely responsible for the increased gluconeogenesis which contributes to fasting hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM). Therefore, to test the hypothesis that an increase in gluconeogenic substrate supply per se could increase hepatic glucose output sufficiently to cause fasting hyperglycemia, we infused normal volunteers with sodium lactate at a rate approximately double the rate of appearance observed in NIDDM while clamping plasma insulin, glucagon, and growth hormone at basal levels. In control experiments, sodium bicarbonate was infused instead of sodium lactate at equimolar rates. In both experiments, [6-3H]-glucose was infused to measure glucose appearance and either [U-14C]lactate or [U-14C]alanine was infused to measure the rates of appearance and conversion of these substrates into plasma glucose. Plasma insulin, glucagon, growth hormone, C-peptide, and glycerol concentrations, and blood bicarbonate and pH in control and lactate infusion experiments were not significantly different. Infusion of lactate increased plasma lactate and alanine to 4.48 +/- 3 mM and 610 +/- 33 microM, respectively, from baseline values of 1.6 +/- 0.2 mM and 431 +/- 28 microM, both P less than 0.01; lactate and alanine rates of appearance increased to 38 +/- 1.0 and 8.0 +/- 0.3 mumol/kg per min (P less than 0.01 versus basal rates of 14.4 +/- 0.4 and 5.0 +/- 0.5 mumol/kg per min, respectively). With correction for Krebs cycle carbon exchange, lactate incorporation into plasma glucose increased nearly threefold to 10.4 mumol/kg per min and accounted for about 50% of overall glucose appearance. Alanine incorporation into plasma glucose increased more than twofold. Despite this marked increase in gluconeogenesis, neither overall hepatic glucose output nor plasma glucose increased and each was not significantly different from values observed in control experiments (10.8 +/- 0.5 vs. 10.8 +/- 0.5 mumol/kg per min and 5.4 +/- 0.4 vs. 5.3 +/- 0.3 mM, respectively). We, therefore, conclude that in normal humans there is an autoregulatory process independent of changes in plasma glucose and glucoregulatory hormone concentrations which prevents a substrate-induced increase in gluconeogenesis from increasing overall hepatic glucose output; since this process cannot be explained on the basis of inhibition of gluconeogenesis from other substrates, it probably involves diminution of glycogenolysis. A defect in this process could explain at least in part the increased hepatic glucose output found in NIDDM. PMID- 2200806 TI - Evidence for a switching mechanism in the invasion of erythrocytes by Plasmodium falciparum. AB - The human malaria parasite Plasmodium falciparum demonstrates variability in its dependence upon erythrocyte sialic acid residues for invasion. Some lines of P. falciparum invade neuraminidase-treated or glycophorin-deficient red blood cells poorly, or not at all, while other lines invade such cells at substantial rates. To explore the molecular basis of non-sialic acid dependent invasion, we selected parasite lines from a clone (Dd2) that initially exhibited low invasion of neuraminidase-treated erythrocytes. After maintaining Dd2 for several cycles in neuraminidase-treated erythrocytes, parasite lines were recovered that invaded both untreated and neuraminidase-treated erythrocytes at equivalently high rates (Dd2/NM). The change in phenotype was maintained after removal of selection pressure. Four subclones of Dd2 were isolated and each readily converted from sialic acid dependence to non-sialic acid dependence during continuous propagation in neuraminidase-treated erythrocytes. The neuraminidase-selected lines and the Dd2 clone demonstrated identical restriction fragment length polymorphism markers indicating that the Dd2 clone was not contaminated during the selection process. Parasite proteins that bound to neuraminidase-treated and untreated erythrocytes were indistinguishable among the parent Dd2 clone and the neuraminidase-selected lines. The ability of the Dd2 parasite to change its invasion requirements for erythrocyte sialic acid suggests a switch mechanism permitting invasion by alternative pathways. PMID- 2200807 TI - Separation of sublethal and lethal effects of polymorphonuclear leukocytes on Escherichia coli. AB - Escherichia coli ingested by PMN promptly stop growing and form no colonies in nutrient agar, but metabolize near normally for up to several hours. The bactericidal/permeability increasing protein (BPI) of PMN also inhibits E. coli growth without initial metabolic impairment. We recently showed that BPI-treated E. coli, although unable to grow in normal nutrient agar, can form colonies in this medium plus 0.1% BSA, as long as their metabolism is maintained, indicating that biochemical impairment is a better indicator of death than growth arrest (1990. J. Clin. Invest. 85:853-860). We have now reexamined the fate of ingested E. coli. Rabbit PMN ingest greater than 85% of several rough E. coli strains in 15 min, but greater than 80% of these bacteria, while unable to form colonies in conventional agar, grow normally on agar plus 0.1% BSA. Thus, the PMN under these conditions promptly stop growth of ingested E. coli without killing. Adding nonlethal concentrations of normal human serum (NHS) before, but not after ingestion, accelerates killing and, in parallel, loss of bacterial metabolism (t1/2 less than 0.5 h vs. greater than 3 h, respectively, with and without NHS). The rapid killing of both rough and smooth E. coli pretreated with NHS is lost after C7 depletion (C7-D) and restored when C7 is replenished. Similar results are obtained with human PMN. In contrast, ingested Staphylococcus epidermidis, opsonized with either NHS or C7-D serum rapidly stop metabolizing and do not form colonies in nutrient agar with or without BSA. Respiratory burst activity is the same during ingestion of E. coli (with or without NHS) and S. epidermidis. Killing of E. coli J5 (however, not of O111-B4) by BPI is also accelerated by pretreatment with NHS but not C7-D human serum. These findings indicate that late complement components are needed for efficient killing of both rough and smooth E. coli by PMN, and that BPI is the principal intracellular agent acting on ingested rough E. coli. PMID- 2200809 TI - Influence of gonadotropin-releasing hormone and timing of insemination relative to estrus on pregnancy rates of dairy cattle at first service. AB - The objective was to determine the influence of gonadotropin-releasing hormone on pregnancy rates of dairy cattle at first services, when both the timing of hormone injection and insemination were altered relative to the onset of estrus. Cows (n = 325) were assigned randomly to six groups making up a 2 X 2 X 2 incomplete factorial experiment; dose of GnRH (100 micrograms versus saline), timing [1 h (early) or 12 to 16 h (late) after first detected estrus] of AI, and timing of hormone injection (early versus late) were the three main effects. Cows were observed for estrus 4 times daily. Treatments and resulting pregnancy rates were: 1) hormone injection early plus AI early (35%), 2) hormone injection late plus AI early (34%), 3) saline injection early plus AI early (30%), 4) hormone injection late plus AI late (30%), 5) hormone injection early plus AI late (46%), and 6) saline injection late plus AI late (43%). Pregnancy rate in the first four groups (32%) was less than that in the latter two groups (44%). Concentrations of LH in serum were greater for cows given hormone or saline injections in early estrus than for cows injected with either hormone of saline during late estrus. Concentrations of LH in serum 2 h after GnRH were elevated above those of controls, whether GnRH was injected during early or late estrus. Neither concentrations of LH during estrus nor concentrations of progesterone 8 to 14 d after estrus explained the possible antifertility effect of GnRH given during late estrus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2200808 TI - Effect of a high-carbohydrate, low-saturated-fat diet on apolipoprotein B and triglyceride metabolism in Pima Indians. AB - The mechanisms by which high-carbohydrate, low-saturated-fat diets lower LDL cholesterol (LDLC) concentrations are unknown. In this study, kinetics of VLDL, intermediate density lipoprotein (IDL), and LDL apoprotein B and VLDL triglyceride were determined in seven nondiabetic (ND) and seven non-insulin dependent diabetic (NIDDM) Pima Indian subjects on high-fat and high-carbohydrate (HICHO) diets. Metabolic changes were similar in ND and NIDDM. On the HICHO diet, LDLC decreased (131 +/- 8 vs. 110 +/- 7 mg/dl, P less than 0.0001) in all subjects. Mean fasting and 24-h triglyceride (TG) concentrations were unchanged, as were mean production rates and fractional clearance rates (FCR) of VLDL apoB and VLDL TG. The mean VLDL apoB pool size (303 +/- 20 vs. 371 +/- 38 mg, P = 0.01) increased owing to a decrease in the mean transport rate (10.7 +/- 1.1 vs. 8.4 +/- 0.9 mg/kg fat-free mass (ffm) per day, P less than 0.0001) and the mean rate constant (2.3 +/- 0.2 vs. 1.5 +/- 0.2, P less than 0.001) for the VLDL apoB to IDL apoB conversion pathway. The mean transport rate of VLDL apoB to LDL apoB via IDL (10.2 +/- 0.9 vs. 8.0 +/- 0.8 mg/kg ffm per day, P less than 0.001) decreased. Mean LDL apoB concentrations decreased (70 +/- 5 vs. 61 +/- 5 mg/dl, P less than 0.001) on the HICHO diet. Means for total LDL apoB transport rate, LDL apoB FCR, and LDLC/apoB ratios were unchanged. In summary, the HICHO diet decreased the activity of mechanisms that convert VLDL to LDL, which contributed to the decrease in LDLC in all subjects. There was also evidence in some subjects for increased activity of LDL apoB clearance mechanisms, and a decrease in the LDLC to apoB ratio. PMID- 2200810 TI - Growth of Escherichia coli in milk from endotoxin-induced mastitic quarters and the course of subsequent experimental Escherichia coli mastitis in the cow. AB - The objective of this study was to assess growth of Escherichia coli in milk from endotoxin-induced mastitic quarters and to relate the in vitro findings to the course of experimental E. coli mastitis. Whole and skim milks from 24 rear quarters of 12 cows were inoculated with E. coli 0:157 and incubated at 38 degrees C. Growth of E. coli 0:157 was not inhibited in milk collected from rear quarters immediately prior to endotoxin infusion. However, growth inhibition occurred in all but one whole mastitic milk samples collected from mastitic quarters 18 h after infusion of .1 mg of endotoxin. Skim milk samples from mastitic quarters were bactericidal in four cows (7 quarters), whereas growth occurred in skim mastitic milk from 17 quarters of nine cows. Rear quarters of all cows were inoculated with 10(4) cfu of E. coli 0:157 19 h after the quarters had been infused with endotoxin. Clinical parameters and milk production were monitored during 36 h and 21 d, respectively. None of the inoculated quarters developed signs of inflammation, and secreta from inoculated quarters were bacteriologically negative after 48 h. Therefore, growth-inhibitory property of skim milk from endotoxin-induced quarters was apparently not a suitable parameter to monitor differences in susceptibility to E. coli mastitis. PMID- 2200811 TI - Effects of feeding frequency and exogenous somatotropin on lipolysis, hormone profiles, and milk production in dairy cows. AB - Effects of feeding frequency and exogenous bovine somatotropin on lactational performance and hormone profiles were examined with 12 multiparous Holstein cows. At 45 d postpartum, cows were assigned to one of two feeding systems. Concentrates were offered in two equal portions at 0800 and 1600 h or in 12 equal portions at 2-h intervals. Chopped alfalfa hay (2.6 kg/d) and barley silage (ad libitum) were fed at 0900 and 1500 h. At 136 d postpartum, cows within each feeding frequency were assigned in a single crossover design to injection of 30 mg of bST/d or solubilization vehicle. Feeding frequency did not influence any of the parameters measured nor did bST interact with feeding frequency. Somatotropin injection increased daily milk yield of cows by 4.4 kg and concentrations of fat and lactose in milk. Protein concentration and fatty acid composition of milk were not influenced by bST injection. Average plasma somatotropin concentrations were elevated threefold, peak concentrations were increased sevenfold, and concentrations at 48 h postinjection were 1.5 times control values. Plasma insulin concentrations were decreased by bST treatment. Results indicate that responses to short-term bST injection are not influenced by feeding frequency. PMID- 2200812 TI - Effect of yeast culture on nutrient digestibility and milk yield response in early- to midlactation dairy cows. AB - Twenty Holstein dairy cows in early lactation were allocated equally to one of two treatments on the basis of age, days in milk, and mean daily 2-wk pretrial milk yield. All animals were fed a total mixed ration; the ration for the treatment group was top-dressed with 90 g/d of yeast culture, Saccharomyces cerevisiae. Treatment period lasted 10 wk. Mean daily DM intake, milk production, milk composition, and BW were not significantly affected by treatment. Feed and fecal samples were collected the last 3 d of the treatment period to determine apparent total tract nutrient digestibility using ADF insoluble ash as the inert marker. No significant differences in digestibility were observed between treatment groups for CP, ADF, and NDF. PMID- 2200813 TI - An overview of food safety issues relative to animal products. AB - Presently, strategies for discovering new factors for enhancing animal productivity allow for greater assurance of food safety. A high degree of assurance of food safety is provided by the use of natural growth factors. This is especially true when these factors are proteins which, when ingested, are digested to inactive peptides and amino acids and are, in addition, inactive in human tissues. Knowing the mechanisms of activity of such factors also allows for the assurance that known mediators of the growth factors can also be shown to be inactivated by intestinal barriers. The design of nonpeptide molecules with highly selective activity will be possible with the large amount of progress expected in understanding the structure of the active components of natural molecules and the availability of specific receptor systems. Food safety concerns may be met by the demonstration that these molecules are inactive in comparable human receptor systems. These drug discovery strategies can ensure with a high degree of confidence the development of new productivity enhancers that meet food safety requirements. PMID- 2200814 TI - Concerns of microbial pathogens in association with dairy foods. AB - Recent outbreaks of foodborne disease linked to Salmonella, Listeria, and Yersinia have highlighted consumer awareness of microbiological problems in the food supply. Such outbreaks affirm the need for improved testing, environmental monitoring, and epidemiological surveillance. This paper reviews the entry of microbial pathogens into foods, with an emphasis on dairy products, by examining the contribution of the processing environment to microbial contamination. Numerous surveys, including a recent audit of dairy processing plants in Vermont, have revealed common foci of environmental contamination by Listeria and Yersinia persistent within dairy processing environments. With respect to dairy products, the bacterial pathogens discussed in this manuscript share a common source, raw milk. Characteristics possessed by Salmonella, Listeria, and Yersinia are compared and contrasted. In the case of Listeria, this bacterium's role as a newly emerged foodborne pathogen is discussed. Finally, the economic consequences associated with foodborne disease are highlighted, and future prospects related to foodborne illness are presented. PMID- 2200815 TI - Economic implications of a safe food supply. PMID- 2200816 TI - Uses of biotechnology and technology transfer to keep food safe. AB - The era of biology is composed of 1) the definition of molecular laws of biology, 2) the exponential expansion of the data base, and 3) the establishment of the first generation molecular and cellular tool kit; this era is driving the development and commercialization of biotechnological products and processes for agriculture and the food system. These products and processes should have a major impact in maintaining and improving food safety. Several meeting and organizational initiatives on biotechnology and food safety are summarized. Possible roles of biotechnology in areas of food safety involve microbial contaminants, nutritional quality, natural antimetabolites, allergens, toxicants, and synthetic chemical residues. Biotechnology will have an impact on all these areas through both improved ability to measure as well as to modify microbes, animals, and plants used as food. Diagnostics for microbial contaminants and biobased alternatives to synthetic chemicals are most advanced. However, all these biotechnological products and processes for food safety are in very early stages of development and commercialization. PMID- 2200817 TI - Mutans streptococci, oral hygiene, and caries in an adult Swedish population. AB - The objective of the present study was to describe the distribution of salivary mutans streptococci in a randomly selected adult population and to relate the distribution to the prevalence of caries. The aim was also to study the association between caries and different levels of oral hygiene (OH). The results were based on the assessment of caries, dental plaque, and concentration of salivary mutans streptococci in 914 subjects who represented 95% of an age- and gender-stratified population sample of 967 individuals, randomly selected from the total adult population living in Alvsborg County, Sweden. The results showed that the distribution of mutans streptococci among dentate adults not wearing any kind of removable denture(s) was similar to that previously reported from studies on Swedish schoolchildren, while a comparably higher proportion of subjects with high levels of mutans streptococci was found among the dentate individuals wearing some kind of removable denture(s). Even higher proportions were found among edentulous individuals with complete denture(s). There was a correlation between mutans streptococci concentration in saliva and caries. The subjects with lower concentrations showed a significantly lower mean number of decayed surfaces, compared with the individuals with higher concentrations of mutans streptococci in their saliva. The median OH standard was lower in the older age groups, and there was a higher ratio of decayed surfaces per remaining tooth in those age groups, in comparison with the younger groups. However, for individuals without mutans streptococci, no relation between OH standard and caries could be found and, regardless of OH standard, higher numbers of decayed surfaces were found with an increasing concentration of mutans streptococci in saliva. PMID- 2200818 TI - A confocal microscopic study of some factors affecting the adaptation of a light cured glass ionomer to tooth tissue. AB - Vitrabond consists of a conventional glass ionomer, in conjunction with a light curing resin and hydroxy-ethylmethacrylate. This study, which used a tandem scanning reflected light microscope for confocal imaging, looked at factors affecting the adaptation of this material to tooth tissue. Wedge-shaped cervical cavities were cut and restored in three ways: (1) Vitrabond was applied as a thin sub-base and either extended onto the enamel margin or kept clear of it. P50 resin composite was then placed, following phosphoric-acid-etching of the enamel margins. (2) The dentin surfaces were conditioned with Scotchprep (maleic acid), then with the Vitrabond, the enamel was etched, and the Scotchbond 2 adhesive applied prior to addition of the P50. (3) Vitrabond was applied alone in bulk, with and without Scotchprep acid-dentin conditioning with a 1:1 (normal) and 3:1 powder:liquid ratio (P:L). Adaptation of the Vitrabond was excellent when maleic acid was used for conditioning of the dentin. When the Vitrabond was used with P50 but extended onto the enamel, the enamel margin occasionally failed. Enamel invariably fractured when the Vitrabond was used alone in bulk. An increase in the P:L ratio decreased contraction gaps when the dentin was not conditioned, but Vitrabond failed cohesively when the dentin was conditioned. The Vitrabond was very susceptible to shrinkage on dehydration. This study suggests that Vitrabond should only be applied to dentin in thin layers, should not be extended onto enamel margins, and should not be allowed to dehydrate. Maleic acid conditioning of the dentin improved adaptation. PMID- 2200819 TI - Persistence of increased nonspecific bronchial reactivity in allergic children and adolescents. AB - Nonspecific bronchial reactivity (BR) is commonly associated with asthma. It can be found, however, in subjects with allergic rhinitis. Studies have not been done looking at changes in nonspecific BR in allergic children over time. Therefore, we report on our longitudinal study of BR in allergic children and adolescents. The reported subjects are part of a larger ongoing study in a selected population of families with asthma and of twins. Initiated in 1972, the subjects reported in this study are subjects who have had at least one follow-up visit through 1989 and did not have asthma, but had allergic histories at either their initial visit or follow-up visits. Subjects completed a questionnaire, had skin tests, determination of a serum IgE level, and a determination of nonspecific BR with a methacholine challenge. Subjects were 6 years of age or older or 21 years of age or younger at initial visit. Subjects from families with asthma (N = 76; mean age, 12.09 years; +/- 4.6 SD) and twins (N = 36; mean age, 11.81 years; +/- 3.81 SD) were followed longitudinally, and their age at follow-up visits was not restricted. In this study we observed that, of 106 subjects, 66% initially demonstrated nonspecific BR. At their first and second follow-up visits, 70.4% and 61.3% demonstrated persistence of their BR. These data demonstrate that allergic children and adolescents have increased nonspecific BR. There was not a significant loss of BR over time in the studied subjects. PMID- 2200820 TI - A distinct subset of antineutrophil cytoplasmic antibodies is associated with inflammatory bowel disease. AB - Antineutrophil cytoplasmic antibodies (ANCAs) have recently been demonstrated to be of importance in Wegener's granulomatosis and certain other forms of vasculitis associated with glomerulonephritis. With a fixed-cell ELISA, we demonstrated that ANCAs occur in the serum of patients with inflammatory bowel disease (IBD) involving the colon. In a blinded study, sera from 21 of 25 patients with ulcerative colitis (UC) and five of 25 patients with Crohn's disease had binding in the fixed-cell ELISA. The five reactive sera from patients with Crohn's disease were associated with the presence of clear colonic involvement. The presence of ANCA in patients with UC was not influenced by disease distribution or activity. Indeed, such antibodies were present in four subjects with UC more than 5 years after colectomy. The IBD-associated ANCAs were distinct from ANCAs reported in patients with Wegener's granulomatosis since the pattern of staining on indirect immunofluorescence exhibited a nongranular perinuclear distribution (P-ANCA). The P-ANCA observed in IBD did not react with myeloperoxidase and thus was distinct from the P-ANCA observed in vasculitis with cresentric glomerulonephritis. IBD and, in particular, UC, is associated with a distinct subset of P-ANCA, which may have important diagnostic and potential pathophysiologic implications. PMID- 2200822 TI - Nasal provocation challenge. The Committee on Upper Airway Allergy. PMID- 2200821 TI - A dose-ranging study of fluticasone propionate aqueous nasal spray for seasonal allergic rhinitis assessed by symptoms, rhinomanometry, and nasal cytology. AB - Fluticasone propionate is a new glucocorticosteroid with potent topical activity. In a double-blind, randomized, parallel-group study, 423 adult patients with moderate to severe seasonal allergic rhinitis received placebo or fluticasone propionate aqueous nasal spray at doses of 25, 100, or 400 micrograms twice daily (b.i.d.) for 2 weeks. Efficacy was evaluated by nasal symptom scores, nasal airflow, nasal cytology, and global evaluation. All doses of fluticasone propionate were significantly better than placebo in reducing symptoms of seasonal allergic rhinitis. Patients receiving the largest dose of fluticasone propionate (400 micrograms b.i.d.) had a slightly greater reduction (not significant) in symptom scores than patients receiving the smallest dose (25 micrograms b.i.d.). Symptom improvement was evident within 3 days of treatment. Nasal airflow improved in the groups treated with fluticasone propionate, 100 and 400 micrograms b.i.d. Examination of nasal cytograms revealed a striking decrease in both eosinophils and basophils in all three groups receiving active treatment compared with placebo. There were few adverse events and no treatment-related abnormalities in laboratory assays or evaluations of hypothalamo-pituitary adrenocortical axis function. Comparison of treatment groups indicated that fluticasone propionate aqueous nasal spray was as safe as placebo at the doses studied. PMID- 2200823 TI - IL-4 inhibits the expression of IL-8 from stimulated human monocytes. AB - Peripheral blood monocytes are important mediators of inflammation via the generation of various bioactive substances, including the recently isolated and cloned chemotactic peptide IL-8. Through cytokine networking, monocyte-derived cytokines are capable of inducing IL-8 expression from non-immune cells. IL-4, a B and T lymphocyte stimulatory factor, has recently been shown to inhibit monocyte/macrophage function, including the ability to suppress monocyte generated cytokines. We describe the in vitro inhibition of IL-8 gene expression and synthesis from LPS, TNF, and IL-1 stimulated peripheral blood monocytes by IL 4. IL-4 suppressed IL-8 production from stimulated monocytes in a dose-dependent fashion, with partial suppression observed at IL-4 concentrations as low as 10 pg/ml. The IL-4-induced suppressive effects were observed even when IL-4 was administered 2 h post-LPS-stimulation. The IL-4-induced inhibition of IL-8 mRNA expression was dependent on protein synthesis, as the suppressive effects of IL-4 were significantly negated by the addition of cycloheximide. Our findings suggest that IL-4 may be an important endogenous regulator of inflammatory cell recruitment, and adds further support to the potential role of IL-4 as a down regulator of monocyte immune function. PMID- 2200824 TI - Mast cell heterogeneity. Differential synthesis and expression of glycosphingolipids by mouse serosal mast cells as compared to IL-3-dependent bone marrow culture-derived mast cells before or after coculture with 3T3 fibroblasts. AB - The synthesis and intracellular expression of glycosphingolipids by mouse serosal mast cells (SMC) have been characterized by radiolabeling and TLC and by immunodetection in situ. Chromatographic analysis of purified glycosphingolipids from SMC intrinsically labeled with [14C]galactose and [14C]glucosamine hydrochloride revealed the predominant synthesis of only the simplest neutral glycosphingolipid and ganglioside, glucosylceramide and ganglioside GM3, respectively. Intracellular indirect immunofluorescence staining of permeabilized SMC demonstrated the absence of the more complex neutral glycosphingolipids lactosylceramide, globotriosylceramide, globotetraosylceramide, and globopentaosylceramide, the absence of ganglioside GM1, and the presence of ganglioside GM3. By contrast, permeabilized mouse IL-3-dependent bone marrow culture-derived mast cells (BMMC) and mast cells recovered after 21 days of coculture of BMMC with mouse 3T3 fibroblasts expressed lactosylceramide, globotriosylceramide, globotetraosylceramide, ganglioside GM1, and ganglioside GM3, but not globopentaosylceramide intracellularly as determined by immunofluorescence. The findings indicate a loss of biosynthetic capacity and epitope maintenance for glycosphingolipids with in vivo differentiation of SMC from IL-3-dependent BMMC progenitors. Thus, although mast cells derived after coculture of these progenitors for 21 days with fibroblasts assume multiple SMC like properties in terms of their histochemical staining and their secretory granule proteoglycan and neutral protease constituents, they do not lose the ability to express complex glycosphingolipids. The finding that glycosphingolipid composition does not change coordinately with other secretory granule markers defines a new stage of mouse mast cell development between the BMMC and SMC and provides evidence that mast cell development is more complex than previously appreciated. PMID- 2200825 TI - Rate and mechanism of generation of beta 2-microglobulin mutants from a heterozygous murine cell line. AB - Mutants that fail to express the B2mb allele can be readily isolated from a B2ma/b heterozygous cell line called R8 by a single step immunoselection protocol using a mAb against beta 2 microglobulin protein in the presence of complement. We present data that demonstrate that the mutants preexist the selection and arise at a rate of about 10(-6)/cell per generation. Southern blot analyses suggest that the mutants have lost the B2mb gene and the linked allele at the Emv 15 proviral integration site telomeric to the B2m locus. Surprisingly, the deletion of the first exon of the B2mb gene that is observed in other cell lines is not found in R8. Possible reasons for this observation are discussed. PMID- 2200826 TI - Once-weekly fluconazole to prevent recurrence of oropharyngeal candidiasis in patients with AIDS and AIDS-related complex: a double-blind placebo-controlled study. AB - Fluconazole 50 mg daily for 14-28 days was effective in the treatment of patients with AIDS and AIDS-related complex with severe oropharyngeal and oesophageal candidiasis. Of 24 patients entered, 17 (81%), including seven with oesophageal candidiasis, were clinically cured and two (9.5%) improved at the end of treatment. Following clinical cure, 14 patients were entered into the double blind phase of the study, where fluconazole (150 mg) or placebo capsules were given once weekly. Treatment was double blind. Fluconazole 150 mg once weekly was found to be effective in maintaining patients both clinically and mycologically free of oropharyngeal candidiasis. PMID- 2200827 TI - Clostridial pleuropulmonary infections: case report and review of the literature. AB - Clostridia rarely cause pleuropulmonary infections in the absence of trauma. We report a case of intermittent bowel obstruction, clostridial bacteraemia and pneumonia with a fatal outcome. Only 16 cases have previously been reported. Clostridial infection of the lung has many features of an acute pneumonia and is almost always associated with a pleural effusion. Most cases are caused by Clostridium perfringens, though infections with other species have been reported. The prognosis is generally more favourable than in clostridial infection secondary to aspiration pneumonia or complicating empyema. PMID- 2200828 TI - Influence of human immunodeficiency virus infection on treponemal serology, in patients who have been treated for syphilis. AB - Sera from 20 homosexual men who were infected with the human immunodeficiency virus (HIV) and had been treated previously for syphilis, were examined for cardiolipin and treponemal antibodies by the Venereal Diseases Research Laboratory (VDRL) test, and the Treponema pallidum haemagglutination assay (TPHA) and fluorescent treponemal antibody absorbed test. In only one case was probable reactivation of syphilis, as judged by rising titres in the VDRL test, noted. PMID- 2200829 TI - Relationship between Merkel cells and nerve endings during embryogenesis in the mouse epidermis. AB - Close relationships between Merkel cells (MC) and nerve endings (NE) exist in the adult mouse. Because MC may serve as targets for the ingrowth of NE during embryogenesis, the purpose of the present study was to analyze the relationship between MC and NE during embryogenesis. Frozen tissue from whisker pads and backs of NMRI mouse embryos (12-17 d gestational age) were studied by double-labeling indirect immunofluorescence (IIF) with a cytokeratin monoclonal antibody that recognizes MC and with a neurofilament anti-serum. Such an approach allowed the analysis of a large number of MC (up to 5000), thus yielding quantitative data. At day 12 of gestational age, no MC were observed by IIF. From day 13 to 17, the number of MC, as well as their association with NE, progressively increased. On day 13, only 57% of whisker pad MC were NE associated, whereas by day 17, 95% were NE associated. These results were confirmed by electron microscopic (EM) observations. On the back, the same chronologic relationship between MC and NE was observed, but was later in the course of embryogenesis. There was also a time and zone-dependent increase in MC association with NE in the epidermal zones studied (isthmic, parafollicular, interfollicular). These observations 1) establish the time course of MC and NE contacts during embryogenesis in the mouse epidermis, 2) show that MC are present in the epidermis and appendages before NE reach the epithelium, and 3) support the hypothesis that MC could act as targets for the growing NE. PMID- 2200831 TI - Image analysis cytometry of dysplastic nevi. AB - Computerized image analysis was used to assess nuclear atypia in 24 dysplastic nevi (DN), 19 CN (CN), and five thin melanomas. DN were selected for the study using architectural criteria alone. Feulgen-stained, 6-um sections were analyzed with a microTICAS cytometer. At least 100 nuclei were measured in each case. The standard deviation of nuclear area, mean nuclear roundness, standard deviation of nuclear roundness, mean ploidy, and standard deviation of ploidy were found to be significantly greater for DN than for CN. DNA histograms from DN showed an increased fraction above 2N, suggesting that DN are more proliferative than CN. No DN were aneuploid. All melanomas were aneuploid, and differed significantly from DN in mean nuclear area, standard deviation of nuclear area, mean ploidy, and standard deviation of ploidy. There were no significant differences between the junctional and intradermal populations of compound DN in any of the measured parameters, except that the intradermal nuclei were significantly rounder than the junctional nuclei. There were no significant differences between DN from patients with only a single DN and DN from patients with at least two dysplastic nevi. PMID- 2200830 TI - Partial cDNA cloning of the 230-kD mouse bullous pemphigoid antigen by use of a human monoclonal anti-basement membrane zone antibody. AB - A cDNA clone with the coding sequence for the 230-kD bullous pemphioid (BP) antigen was isolated from a mouse cDNA expression library by using an anti basement membrane zone human monoclonal antibody (MoAb-5E). The lambda gt11 cDNA expression library was constructed from poly(A)+RNA from the mouse epidermal cell line, Pam cells, by random priming. 1.5 X 10(5) recombinant clones were screened by immunostaining with MoAb-5E and one positive clone (BPM1) was obtained. All of the ten BP sera but none of the five normal or seven pemphigus sera tested reacted with the fusion protein produced by BPM1. The size of the cDNA was 3.2 kb. Northern blot analysis indicated that BPM1 cDNA hybridized to a mRNA of about 9 kb, which is large enough to encode for a 230-kD protein. DNA sequencing demonstrated a 2,991-bp open reading frame encoding a peptide of 115 kD. Sequence comparison between mouse and human cDNA clones revealed that the 230-kD BP antigen was well conserved during evolution except for the carboxyl terminus. Highly conserved and hydrophilic regions in the molecule were considered to be good candidates for antigenic determinants. This cDNA clone will be useful not only for diagnosis of BP, e.g., enzyme-linked immunosorbent assay using recombinant proteins or synthetic peptides as antigens, but also for pathophysiologic study in which mouse models of BP might be used. PMID- 2200832 TI - Recombinant equine interferon-beta 1: purification and preliminary characterization. AB - Equine interferon-beta 1 (EqIFN-beta 1) was purified from extracts of recombinant Escherichia coli by sequential chromatography on hydroxylapatite, anion-, and cation-exchangers. The resulting protein was greater than 98% pure as determined by sodium dodecylsulfate gel electrophoresis, gel permeation HPLC, and reverse phase HPLC. Amino-terminal amino acid sequencing revealed that essentially all molecules contained an additional amino-terminal methionine. The specific antiviral activity of EqIFN-beta 1 determined on equine dermal fibroblasts challenged with vesicular stomatitis virus (VSV) was approximately 5 X 10(8) U/mg. Less than 0.001% of this activity was observed in antiviral assays using human (A549), murine (L-M), ovine (SCP), or bovine (MDBK and BT) cells challenged with VSV or encephalomyocarditis virus. A series of monoclonal murine IgG antibodies were developed which neutralize the antiviral activity of EqIFN-beta 1. None of these antibodies nor rabbit antiserum to EqIFN-beta 1 were able to neutralize human IFN-beta; antiserum to human IFN-beta did not neutralize EqIFN beta 1. Two of the monoclonal antibodies were used to establish a rapid one-step solid-phase enzyme immunoassay for EqIFN-beta 1. PMID- 2200833 TI - Postoperative patient-controlled analgesia with alfentanil: analgesic efficacy and minimum effective concentrations. AB - Forty ASA I-III patients recovering from major abdominal or orthopedic operations were investigated in an open clinical study to evaluate analgesic efficacy and threshold plasma concentrations of alfentanil during the early postoperative period using patient-controlled analgesia (PCA) by means of the On-Demand Analgesia Computer. Alfentanil demand dose was 212 micrograms, continuous infusion rate 25 micrograms/hr, hourly maximum dose 1.5 mg/hr; the lockout time was set to 1 min. The duration of PCA was 18.1 +/- 5.2 hr (mean, SD) during which time 23.8 +/- 14.2 demands per patient were recorded, resulting in an average alfentanil consumption of 4.99 +/- 3.03 micrograms/kg/hr. Patient acceptance of PCA was high. Side effects were only of minor intensity and never gave rise to concern. Based on our own earlier PCA experience with other opiate analgesics, alfentanil proved to be about 1/15th as potent an analgesic as fentanyl and about 6-7 times more potent than morphine if both intensity and duration of effect were considered. Minimum effective alfentanil plasma concentration (MEC) varied greatly and could be best described by a lognormal distribution (range 0.6-99.2 ng/mL, median 14.9 ng/mL). Intraindividual MEC variability was consistently lower than intersubject variability (37.0% vs 65.2%). PMID- 2200834 TI - Pott's puffy tumour reviewed. AB - The aim of this paper is to highlight Potts puffy tumour as a pathological entity distinct from other causes of peri- and supraorbital swelling. This uncommon condition is usually not recognised initially and is easily confused with neoplasms or local eye pathology. A case is reported and investigations and management reviewed. PMID- 2200835 TI - Membership directory. Society for Leukocyte Biology. PMID- 2200836 TI - Eighty-year-old men without cardiovascular disease in the community of Malmo. Part II. Smoking characteristics and ultrasound findings, with special reference to glutathione transferase and pyridoxal-5-phosphate. AB - A total of 1280 80-year-old men in the community of Malmo were questioned about smoking habits and the occurrence of cardiovascular disease (CVD). After a careful medical and duplex ultrasound examination, four groups were selected for further studies: (1) no CVD, non-smokers: (2) no CVD, smokers: (3) CVD, smokers: (4) CVD, non-smokers. In total 122 individuals participated. The average tobacco consumption by smokers was 13 g d-1 for 59 years. In the CVD group 45% of subjects had atherosclerotic symptoms at more than one site. Smoking was found to be correlated with lower extremity atherosclerosis, cholesterol and LDL cholesterol were correlated with carotid artery lesions and pathological ankle/arm index, and blood pressure was correlated with lower extremity lesions. In contrast with middle-aged populations, individuals with an increasing degree of lesions in the lower extremities had a larger percentage of high glutathione transferase activity than subjects without CVD. Smokers had significantly lower pyridoxal-5-phosphate levels than non-smokers. It is concluded that some heavy smokers might reach an advanced age in good health. Smoking was also operative as a risk indicator for lower extremity atherosclerosis in 80-year-old individuals. PMID- 2200837 TI - Management of cholesterol gallstones--are there alternatives to cholecystectomy? PMID- 2200838 TI - Insulin sensitivity in alcoholics in a withdrawal state. AB - Insulin sensitivity in non-diabetic alcoholics in a withdrawal state was investigated using a euglycaemic clamp technique on two occasions with an interval of 1 week. Insulin was infused at a rate of 40 mU m-2 min-1 (n = 9) and 20 mU m-2 min-1 (n = 9). Hepatic glucose production was estimated with tritiated glucose in six subjects. The fasting glucose level at the first examination, 5.1 +/- 0.2 mmol l-1, exceeded that found at the second examination, 4.7 +/- 0.1 mmol l-1 (P less than 0.05), although the C-peptide concentration was higher at the first examination (2.7 +/- 0.3 vs. 1.6 +/- 0.2 ng ml-1; P less than 0.001). Both glucose uptake (5.0 +/- 0.6 vs 6.2 +/- 0.7 mg kg-1 min-1; P less than 0.05) and tissue sensitivity (M/I; 0.08 +/- 0.02 vs. 0.1 +/- 0.02 mg kg-1 min-1/mU l-1; P less than 0.05) increased between the first and second euglycaemic clamp (40 mU m 2 min-1). At the low insulin infusion rate (20 mU m-2 min-1), the tissue sensitivity to insulin increased (0.09 +/- 0.01 vs. 0.13 +/- 0.02 mg kg-1 min 1/mU l-1; P less than 0.05). Hepatic glucose production did not change during the examination period (2.2 +/- 0.2 vs. 2.3 +/- 0.1 mg kg-1 min-1), neither was there a change in the suppression of hepatic glucose output during hyperinsulinaemia (40 mU m-2 min-1). Our findings indicate that, in non-diabetic alcoholics, insulin sensitivity in peripheral tissues is decreased during the early part of a withdrawal period. PMID- 2200839 TI - Dynamics of plasmid transfer on surfaces. AB - A protocol was developed to study the dynamics of growth and plasmid transfer in surface populations of bacteria. This method allows for quantitative estimates of cell population densities over time, as well as microscopic observations of colony growth and interactions. Using this 'surface slide system' (SSS), the dynamics of the plasmid R1 and its permanently derepressed mutant R1drd19 in surface cultures of Escherichia coli K12 was examined. In surface culture, the stationary-phase cell densities were constant over a wide range of initial cell density (= colony density) and comparable to those obtained in liquid culture. For high initial cell densities, where the cells formed a confluent layer at stationary phase, the kinetics of growth and plasmid transfer was similar to that obtained in liquid culture, and the relative yields of R1drd19 and R1 transconjugants were similar in the two habitats. In surface culture, however, R1drd19 transconjugant yield was profoundly affected, and R1 transfer to a lesser extent, by colony density. In contrast, liquid matings were virtually unaffected by initial cell density. The transfer advantage of the permanently depressed over the repressed plasmid was much less apparent for lower colony densities. I propose a hypothesis for plasmid transfer between colonies that explains these observations as a consequence of the geometry of the surface habitat and the effect of transitory derepression of the synthesis of pili. PMID- 2200840 TI - Purification and properties of NADP(+)-dependent glycerol dehydrogenases from Aspergillus nidulans and A. niger. AB - Glycerol dehydrogenase, NADP(+)-specific (EC 1.1.1.72), was purified from mycelium of Aspergillus nidulans and Aspergillus niger using different purification procedures. Both enzymes had an Mr of approximately 38,000 and were immunologically cross-reactive, but had different amino acid compositions and isoelectric points. For both enzymes, the substrate specificity was limited to glycerol and erythritol for the oxidative reaction and to dihydroxyacetone (DHA), diacetyl, methylglyoxal, erythrose and D-glyceraldehyde for the reductive reaction. The A. nidulans enzyme had a turnover number twice that of the A. niger enzyme at pH 6.0, whereas inhibition by NADP+ was less (Ki = 45 microM vs 13 microM). It is proposed that both enzymes catalyse in vivo the reduction of DHA to glycerol and that they are regulated by the anabolic reduction charge. PMID- 2200841 TI - Internalization of lucifer yellow in Candida albicans by fluid phase endocytosis. AB - Lucifer yellow (LY), an impermeable fluorescent dye used as a marker for fluid phase endocytosis, was internalized by Candida albicans. As observed by fluorescence microscopy, incubation of C. albicans with LY in potassium phosphate buffer (pH 6.0) and glucose (2%, w/v) resulted in localization of the dye inside vacuoles. Sodium azide and carbonyl cyanide m-chlorophenylhydrazone, which are inhibitors of energy metabolism, decreased the uptake of the dye. The optimum temperature for uptake was 30 degrees C; no internalization was observed at 0 degrees C. Quantification of cell-associated LY by fluorescence spectrometry showed an uptake linear with time and not saturable over a 400-fold range of concentration. Thus, C. albicans internalized LY into vacuoles by a nonsaturable and time-, temperature- and energy-dependent process consistent with fluid phase endocytosis. Both the yeast and mould phase of this dimorphic fungus endocytosed LY. Growth in complex medium appeared to be required to enable the cells to internalize LY. However, addition of peptone or yeast extract to the phosphate buffer/glucose assay medium interfered with LY uptake by causing an apparent increase of exocytosis. These studies provide the first evidence of fluid phase endocytosis in C. albicans and may explain how some large molecules, such as toxins and cationic proteins, enter C. albicans. PMID- 2200842 TI - The role of microfilaments and microtubules in apical growth and dimorphism of Candida albicans. AB - Cytoskeleton inhibitors were used to study morphogenesis in the pathogenic and dimorphic fungus Candida albicans. Nocodazole is a specific microtubule inhibitor and chloropropham (CIPC), at high concentrations, is an inhibitor of microtubules and microfilaments. Distribution of microtubules and microfilaments was studied by immunofluorescence techniques using anti-tubulin antibody with FITC-conjugated secondary antibody, and by staining with Rh-phalloidin. Nocodazole did not arrest apical cell elongation at a concentration (20 micrograms ml-1) that inhibited nuclear division and migration. Cytoplasmic and nuclear microtubules disappeared within 30 min in filamentous cells under these conditions. However, the Rh phalloidin-stained actin granules which were localized in the tips of filamentous cells, and the microfilaments, were arranged normally at this concentration of nocodazole. Growth, and normal distribution of microtubules and microfilaments, were inhibited by a high concentration (200 micrograms ml-1) of CIPC. At a concentration (100 micrograms ml-1) of CIPC that permitted nuclear division, apical cell elongation was arrested, and filamentous growth was converted into yeast growth. At this concentration of CIPC, microtubules were distributed normally in filamentous cells. Long microfilaments were not observed, and actin granules did not localize in the tips of filamentous cells, but were distributed throughout the cytoplasmic cortex. Our results show that cytoplasmic microtubules are not essential for the elongation of filamentous cell tips but that microfilaments are apparently essential for this process. PMID- 2200843 TI - Prevention of Clostridium difficile-induced experimental pseudomembranous colitis by Saccharomyces boulardii: a scanning electron microscopic and microbiological study. AB - The ability of Saccharomyces boulardii to protect mice against intestinal pathology caused by toxinogenic Clostridium difficile was studied. Different regions of the intestine of experimental mice were prepared for observation by scanning electron microscopy or homogenized for C. difficile enumeration and quantification of toxin A by enzyme immunoassay and toxin B by cytotoxicity. The test group was treated for 6 d with an S. boulardii suspension in drinking water and challenged with C. difficule on day 4. The three control groups were: axenic mice, mice treated with only S. boulardii and mice only challenged with C. difficile. The results showed that: (i) 70% of the mice infected by C. difficile survived when treated with S. boulardii; (ii) the C. difficile-induced lesions on the small and large intestinal mucosa were absent or markedly less severe in S. boulardii-treated mice; and (iii) there was no decrease in the number of C. difficile but rather a reduction in the amount of toxins A and B in S. boulardii treated mice. PMID- 2200844 TI - Yersinia enterocolitica immunodominant 60 kDa antigen, common to a broad range of bacteria, is a heat-shock protein. AB - Monoclonal antibodies (mAbs) against the Yersinia enterocolitica immunodominant 60 kDa antigen, termed cross-reacting protein antigen (CRPA), were obtained by fusion of spleen cells from mice immunized with CRPA with murine myeloma cells. The reactivities of the mAbs were examined by Western blotting against extracts of Y. enterocolitica and 23 other species of Gram-positive and Gram-negative bacteria. Cross-reactions were recognized with a wide range of bacteria, but not with Gram-positive cocci. The reactivities were different for each mAb, suggesting that both species-specific and multiple cross-reactive epitopes were present on the CRPA molecule. CRPA was produced under heat-shock conditions in Y. enterocolitica and was shown to correspond immunologically to the GroEL protein in Escherichia coli, a protein involved in the morphogenesis of coliphage. In addition to CRPA, at least nine other major heat-shock proteins were detected by two-dimensional gel electrophoresis of extracts of heat-shocked Y. enterocolitica. PMID- 2200845 TI - Molecular cloning and nucleotide sequence of another variant of the Escherichia coli Shiga-like toxin II family. AB - Escherichia coli strain H.I.8 (O128:B12) produces low levels of a Shiga-like toxin (SLT) which we have called SLTIIva because of its close relationship with SLTIIv. The Vero cell cytotoxicity of SLTIIva is neutralized by antisera against SLTII and SLTIIv but not by antisera against SLTI. These data indicate that the SLT of strain H.I.8 is a member of the SLTII family. Since SLTIIva shares with SLTIIv the property of having low cytotoxicity to HeLa cells compared with Vero cells, it is appropriate to consider both toxins as variants of SLTII. SLTIIva differs from SLTIIv in that it is more heat-stable. Further, SLTIIv-producing strains of E. coli have only been isolated from pigs while the SLTIIva-producing E. coli strain examined in this study was isolated from a human infant with diarrhoea. The genes for this SLT were cloned from a cosmid library of total cellular DNA by screening recombinants for Vero cell toxicity and with a DNA probe derived from SLTIIv structural genes. Nucleotide sequence analysis was performed on a 2.0 kb AvaII-HincII fragment which encodes the toxin gene. The nucleotide sequence data confirm the close relationship between SLTIIva and SLTIIv: they have 98% nucleotide sequence homology in the B subunit gene and 70.6% homology in the A subunit gene. Comparison of DNA sequences indicated that SLTIIva was most closely related to SLTIIv, closely related to SLTII and less closely related to SLTI. PMID- 2200846 TI - Hydrogen autotrophy of Nocardia opaca strains is encoded by linear megaplasmids. AB - Several linear megaplasmids were detected in the facultatively lithoautotrophic Gram-positive bacterium Nocardia opaca. The wild-type strain MR11 contains, in addition to the cccDNA plasmids pHG31-a and pHG31-b, the linear plasmids pHG201 (270 kb), pHG202 (400 kb) and pHG203 (420 kb). The wild-type strain MR22 contains, in addition to the cccDNA plasmid pHG33, the linear plasmids pHG204 (180 kb), pHG205 (280 kb) and pHG206 (510 kb). After preparation of DNA from cells embedded in agarose, the linear plasmids were demonstrated by pulsed-field electrophoresis. By means of DNA probes for genes of soluble hydrogenase and ribulose-bisphosphate carboxylase, the conjugative plasmids pHG201 and pHG205 were shown to be the carriers of the genetic information for these enzymes. A restriction map of pHG201 for the enzymes AsnI, SpeI, XbaI is presented. PMID- 2200847 TI - Restoration of hydrogenase activity in hydrogenase-negative strains of Escherichia coli by cloned DNA fragments from Chromatium vinosum and Proteus vulgaris. AB - DNA fragments from Proteus vulgaris and Chromatium vinosum were isolated which restored hydrogenase activities in both hydA and hydB mutant strains of Escherichia coli. The hydA and hydB genes, which map near minute 59 of the genome map, 17 kb distant from each other, are not structural hydrogenase genes, but mutation in either of these genes leads to failure to synthesize any of the hydrogenase isoenzymes. The smallest DNA fragments which restored hydrogenase activity to both E. coli mutant strains were 4.7 kb from C. vinosum and 2.3 kb from P. vulgaris. These fragments were cleaved into smaller fragments which did not complement either of the E. coli mutations. The cloned heterologous genes also restored formate hydrogenlyase activity but they did not restore activity in hydE, hupA or hupB mutant strains of E. coli. The cloned genes, on plasmids, did not lead to the synthesis of proteins of sufficient size to be the hydrogenase catalytic subunit. The hydrogenase proteins synthesized by hydA and hydB mutant strains of E. coli transformed by cloned genes from P. vulgaris and C. vinosum were shown by isoelectric and immunological methods to be E. coli hydrogenase. Thus, these genes are not hydrogenase structural genes. PMID- 2200848 TI - A retinal ganglion cell neurotrophic factor purified from the superior colliculus. AB - Dissociated neonatal rat retinal ganglion cells can be maintained by the addition of an extract from the neonatal superior colliculus. This extract can support 95% of ganglion cells over 24 h in culture; in addition it promotes the expression of neurites from these cells. This report describes the purification of a neurotrophic factor from the superior colliculus which supports the survival of 80% of retinal ganglion cells over 24 h in vitro. The purification procedure involves a combination of dye-ligand, anion-exchange, and molecular sieve chromatography. The purified neurotrophic factor has a Stokes radius of approximately 200 A using molecular sieve chromatography in the presence of a chaotropic agent. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified factor indicates that it is a glycoprotein that migrates with a molecular mass greater than 400 kDa. Further characterization of this high molecular-mass glycoprotein by enzymatic digestion demonstrated that it is a chondroitin sulfate proteoglycan. This factor is clearly distinguishable from other neurotrophic factors that have an effect on retinal ganglion cells such as brain-derived neurotrophic factor and fibroblast growth factor. The chondroitin sulfate proteoglycan from the neonatal superior colliculus is the first proteoglycan to be identified as a neurotrophic factor. PMID- 2200850 TI - The epidemiological relationship of hypercholesterolemia, hypertension, diabetes mellitus and obesity to coronary heart disease and atherogenesis. AB - Coronary heart disease (CHD) is an imprecise, inappropriate monitor of atherosclerosis severity and by inapplicable extrapolation CHD risk factors are incorrectly assumed to be causes of atherosclerosis. Taking into account (1) the misuse and substantial diagnostic error of CHD, (2) errors in determining the prevalence of risk factors, (3) the use of a young non-representative minority of sufferers of CHD, (4) bias posed by inclusion of familial hypercholesterolemia (FH) in clinical studies and (5) mutual inter-relationships, genetic influence and age dependence of hypercholesterolemia, hypertension, diabetes mellitus and body mass or obesity, it is unlikely that multivariate statistical analyses can adequately differentiate between their effects. These factors are age dependent and so are CHD and atherosclerosis. The importance of hypercholesterolemia in atherogenesis is suspect particularly since the vascular pathology of familial hypercholesterolemia and of cholesterol-fed animals has been misrepresented and does not provide support for the role of hypercholesterolemia in atherogenesis. PMID- 2200849 TI - Metabolic stability of 3-O-methyl-D-glucose in brain and other tissues. AB - 3-O-Methyl-D-glucose (methylglucose) is often used to study blood-brain barrier transport and the distribution spaces of hexoses in brain. A critical requirement of this application is that it not be chemically converted in the tissues. Recent reports of phosphorylation of methylglucose by yeast and heart hexokinase have raised questions about its metabolic stability in brain. Therefore, we have re examined this question by studying the metabolism of methylglucose by yeast hexokinase and rat brain homogenates in vitro and rat brain, heart, and liver in vivo. Commercial preparations of yeast hexokinase did convert methylglucose to acidic products, but only when the enzyme was present in very large amounts. Methylglucose was not phosphorylated by brain homogenates under conditions that converted 97% of [U-14C]glucose to ionic derivatives. When [14C]methylglucose, labeled in either the methyl or glucose moiety, was administered to rats by an intravenous pulse or a programmed infusion that maintained the arterial concentration constant and total 14C was extracted from the tissues 60 min later, 97-100% of the 14C in brain, greater than 99% of the 14C in plasma, and greater than 90% of that in heart and liver were recovered as unmetabolized [14C]methylglucose. Small amounts of 14C in brain (1-3%), heart (3-6%), and liver (4-7%) were recovered in acidic products. Plasma glucose levels ranging from hypoglycemia to hyperglycemia had little influence on the degree of this conversion. The distribution spaces for methylglucose were found to be 0.52 in brain and heart and 0.75 in liver. PMID- 2200851 TI - The utility of indirect measures of obesity in racial comparisons of blood pressure. CARDIA Study Group. AB - The associations between estimates of obesity derived from anthropometric measurements (body mass index, the sum of three skin folds, and the computed percent body fat) and blood pressures were examined by multiple regression analysis in 4508 young black and white adults. The three estimates of obesity yielded similar results in regression analyses. The strength of associations between these three estimates of obesity and systolic and diastolic blood pressures did not differ in black and white subjects of either sex. All three estimates lead to the same interpretation of the relationship between obesity and systolic or diastolic blood pressure. Estimated percent body fat offered no advantage over the other indices in this context. PMID- 2200852 TI - Written case simulations: do they predict physicians' behavior? AB - Written case simulations are often used to investigate physicians' decision making and clinical competence. Their use rests on the assumption that physicians' responses to written simulations closely agree with their responses to actual clinical encounters, yet this assumption of criterion validity has received little attention. To determine the ability of written case simulations to predict actual clinical behavior, we applied methodologic criteria to published articles that used written simulations. Only 11 (15%) of 74 articles included an assessment of the criterion validity of their written case simulations. Only 2 of those 11 studies were designed and executed in such a way that criterion validity could be fully interpreted. No clear consensus emerged from an examination on the 11 studies on how well responses to written case simulations perform as proxy measures of actual behavior. More work is needed before assuming that written case simulations measure actual behavior. PMID- 2200853 TI - The relationship between chi-square statistics from matched and unmatched analyses. AB - The McNemar chi-square statistic for testing the equality of proportions in matched pairs of binary data is expressed as a function of the Pearson chi-square statistic and a kappa statistic for measuring interrater agreement. Implications for data analysis and for sample size determination are discussed. The result is generalized to provide a similar relationship between Cochran's Q-statistic and the Pearson chi-square statistic for the comparison of proportions in matches of size m. PMID- 2200854 TI - Vilhelm Magnus--pioneer neurosurgeon. AB - In parallel with but completely independent from Harvey Cushing, Norway had its own giant in the establishment of the special field of neurological surgery. Vilhelm Magnus (1871-1929), born in the United States in Fillmore County, Minnesota, was Norway's pioneering neurosurgeon. Following graduation in Oslo, he started his clinical training in neurology and became an early member of the small group of neurologists of the time who were dissatisfied with the therapeutic nihilism generally accepted in relation to diseases of the nervous system. After working with Victor Horsley, whom he held in high esteem. Magnus devoted himself to surgically treatable lesions in the nervous system. During a quarter of a century he single-handedly established the special field of neurological surgery in Norway. Magnus was a far-seeing and brilliant surgeon with a broad intellectual mind, a startling diligence, and wide research activities. He published his first scientific paper in 1899 and his total contribution to the literature amounted to 70 papers. In 1901 he was able to demonstrate the importance of the corpus luteum in the first 3 weeks of pregnancy. As early as 1903 Magnus manifested his interest in the surgical treatment of brain tumors. In 1926 his surgical material comprised 216 patients, with an 8% operative mortality rate among 161 cases of supratentorial tumor versus 17% for 55 cases of infratentorial tumors, including 14 cases of acoustic tumor. Vilhelm Magnus, who visited Harvey Cushing in 1928, has hitherto not been given the attention he merits. PMID- 2200855 TI - Presentation and management of suprasellar arachnoid cysts. Review of 20 cases. AB - The clinical presentation and treatment of suprasellar arachnoid cysts remain controversial. The authors review 20 cases treated at their institution and 86 cases from the literature reported in sufficient detail for analysis. The high frequency of endocrinological disorders, which not only persist following treatment but may also develop years later despite the satisfactory decrease in volume of the cyst, are emphasized and documented. The difficulties of management are discussed, including; subfrontal approaches to these cysts; removal and/or marsupialization of the cysts, procedures that are frequently dangerous and ineffective; and ventricular shunting which often leads to a paradoxical increase in the size of the cysts. The authors emphasize the advantages of percutaneous ventriculocystostomy, which is a simple, benign, and efficacious procedure. PMID- 2200856 TI - Cauda equina syndrome of long-standing ankylosing spondylitis. Case report and review of the literature. AB - Cauda equina syndrome as a neurological complication of long-standing ankylosing spondylitis was first reported in 1961. The syndrome is relatively uncommon and its pathophysiology is still poorly understood. Based on their experience with such a case, the authors review the clinical, electrographic, histological, and radiographic features of the syndrome, including the findings of magnetic resonance (MR) imaging. The addition of MR imaging to the evaluation of patients with ankylosing spondylitis and the cauda equina syndrome not only aids in the diagnosis of the syndrome but may also provide valuable insight into the pathophysiology of this condition. PMID- 2200857 TI - Thallium-201 myocardial scintigraphy: single injection, re-injection, or 24-hour delayed imaging? PMID- 2200858 TI - Scientific highlights 1990: the universe within. PMID- 2200859 TI - PET studies of the dopaminergic system. A review. PMID- 2200860 TI - Antibody internalization by tumor cells: implications for tumor diagnosis and therapy. PMID- 2200861 TI - Biodegradable poly(lactic acid) and poly(lactide-co-glycolide) microcapsules: problems associated with preparative techniques and release properties. AB - Poly(lactic acid) [PLA] and its co-polymers with glycolic acid [PLCG] have been known to be biodegradable and histocompatible for the past 20 years. Their physico-chemical and biological properties have been found suitable, in many instances, for sustaining drug release in vivo for days or months. Several dosage forms for parenteral administration have been investigated using these polymers and a microencapsulation technique is chosen frequently for its unique properties. There are a limited number of published papers concerning preparation and characterization of PLA or PLCG microcapsules, possibly because of commercial unavailability and difficulties in the synthesis of reproducible batches of these polymers. However, microcapsules can be made using different traditional and non traditional techniques containing core materials ranging from biological proteins to synthetic drugs. An attempt is made here to review problems associated with the different microencapsulation techniques using PLA or PLCG. In vivo and in vitro drug release from these microcapsules is also reviewed. PMID- 2200862 TI - Normal values of Pulsatility Index from fetal vessels: a cross-sectional study on 1556 healthy fetuses. AB - In a cross-sectional study of 1556 uncomplicated pregnancies velocity waveforms were recorded at the level of fetal umbilical artery, descending aorta, renal artery, internal carotid artery and middle cerebral artery. Reference limits for the Pulsatility Index of each vessel were constructed by regression analysis and a progressive fall during gestation was evidenced in all the vascular districts investigated with the exception of descending aorta. Furthermore we calculated the ratios between Pulsatility Index values of cerebral and peripheral vessels which may be relevant for the early diagnosis of the haemodynamic abnormalities occurring during the brain sparing effect. PMID- 2200863 TI - Transvaginal colour Doppler ultrasound in normal and abnormal early pregnancy. AB - The value of transvaginal colour and pulse wave Doppler in the diagnosis of pathologic early intrauterine and tubal pregnancy was assessed. Forty-one normal pregnancies, 6 blighted ovum, 6 missed abortions, and 22 suspected ectopic pregnancies (13 proven tubal pregnancies) were examined. Single 5 MHz transvaginal colour and pulse wave Doppler probe was used and once clear signals from uterine vessels, umbilical artery or trophoblastic vessels were obtained. Resistance Index (peak systole--end diastole/peak systole, RI) from the corresponding waveforms was calculated. In 41 normal pregnancies (examined before termination of pregnancy) with gestational age ranged from 6 to 10 weeks mean RI in uterine artery was 0.81 (SD 0.06), in the umbilical artery 1 (SD 0), and 0.48 (0.08) in the trophoblastic vessels. Mean RI from uterine arteries in six pregnancies with blighted ovum and six with missed abortion were 0.77 (SD 0.11) and 0.69 (SD 0.13) respectively. In 2 out of 6 cases of blighted ovum and 4 out of 6 cases of missed abortion flow in trophoblastic vessels could not be detected. These findings suggest ineffective early placentation in pathologic pregnancy. Twenty-two patients with suspected ectopic pregnancy (raised serum beta HCG with empty uterus, amenorrhoea with abdominal pain and/or palpable abdominal mass) were examined. In 13 cases tubal pregnancy was confirmed by laparoscopy and/or laparotomy. In the remaining nine cases the diagnosis was excluded by means of laparoscopy or subsequent negative beta HCG. Doppler diagnosis of ectopic pregnancy was made when colour flow in adnexa with RI less than 0.56 was revealed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2200864 TI - The assessment of luteal blood flow in pregnant and non-pregnant women by transvaginal color Doppler. AB - Transvaginal color Doppler of luteal flow was performed on 58 patients with normal early pregnancy before artificial abortion, 73 patients with proven ectopic pregnancy and 75 non-gravid patients in luteal part of menstrual cycle. The equipment used were Aloka Color Doppler SSD-350 and SSD-680 with a 5 MHz transvaginal probe. Obtained color flow from ovarian tissue was explored with pulsed Doppler and the Pourcelot resistance index was calculated. Typical luteal low-impedance flow was detected in 82.8% cases of early pregnancy, 80.8% cases of ectopic pregnancy and 69.3% cases of non-pregnant women. The lowest resistance index (RI = 0.42 +/- 9.12) of luteal flow was found in cases of non-pregnant women, and the highest resistance index (RI = 0.53 +/- 0.09) was obtained in cases of early normotopic pregnancy. RI in cases of ectopic pregnancy was 0.48 +/ 0.07. Statistical analysis has shown significantly different RI in each of 3 groups of patients (P greater than 0.001). Corpus luteum was seen as early as a few days after ovulation in non-pregnant women and was present until about the 11th week of amenorrhea in pregnant women. In 86.4% patients with proven ectopic pregnancy, luteal flow was detected on the same side as the ectopic pregnancy. Our results have shown different RI value of corpus luteum flow in different groups of patients. Such findings could help to exclude pregnancy, specially with non-specific B-mode ultrasound features. Corpus luteum flow could be used as a guide for searching for ectopic pregnancy. PMID- 2200865 TI - When does death occur in an acardiac twin? Ultrasound diagnostic difficulties. AB - Fetal acardia is a rare abnormality of multiple pregnancies, which is lethal for the affected fetus and can cause death in 50% of normal co-twins. Antenatal recognition with early ultrasound is essential to institute a prospective management to improve the outcome. Our communication outline the difficulties which may be encountered in ultrasound diagnosis. In particular the problem of distinguishing a fetal heart from large pulsating mediastinal vessels, which can be present in these fetuses, and the difficulty of diagnosing death in an acardiac fetus. Our report confirms that the co-twin remains at increased risk of sudden death, even without ultrasound evidence of cardiac failure or biochemical compromise. The finding in this fetus of intravascular fibrin deposits suggests the possibility of acute disseminated intravascular coagulation, not previously reported in association with an acardiac twin. PMID- 2200866 TI - Plasma renin activity in fetal disease. AB - Fetal plasma renin activity (PRA) was measured in 42 pregnancies. Compared to control fetuses, PRA was elevated in three of four hypoxemic fetuses, in two of five with hydrops and in two of five with uropathies. PRA did not change with transfusion in seven alloimmunized fetuses. This study demonstrates PRA in human fetuses and suggests that the renin-angiotensin system can respond to stimuli in fetal life. PMID- 2200867 TI - Backscattered electron imaging: the role in calcified tissue and implant analysis. AB - The working distance and tilt studies helped to clarify the influences of specimen variability when the BSE mode is used in calcified tissue research. This work has shown that the BSEPs of cortical bone may be accurately maintained within 2 percent error over a 10 degree range of tilt, or 300 microns working distance variation. If future bone and implant investigators wish to conduct accurate, quantitative mineral microanalysis in bone, then standard grinding and polishing techniques should be adequate if calibration procedures are developed. The BSEP characteristics of the pure metals make them suitable to be used for calibrating the BSE signal. BSE analysis, with correlated biomechanical studies, will lead us to a better understanding of the relationships between structure, function, and mineral content in bone. On-line BSEP analysis techniques will expand our understanding of the mineralization events in bone which are associated with aging, weightlessness, pharmaceutical therapies, and the presence of biomaterials. The future of the BSE imaging technology and the contributions to be made in understanding the histometry, biomechanics and mineral content of bone as well as bone's response to implant materials has just begun to unfold. PMID- 2200868 TI - Kinetics of hemolysin production in bovine group B streptococci. AB - Thirteen strains of group B streptococci etiologically related to bovine infections were investigated in order to observe the effects of non-hemoglobin iron and glucose on growth and hemolysin production; and to determine the necessity to stabilize the hemolysin with a carrier-stabilizer agent. Ferric citrate was diluted to give final concentrations of 1-11 micrograms/ml, added to iron-reduced (by CaCl2 precipitation) brain heart infusion media, inoculated and incubated at 37 degrees C. Parallel experiments were carried out with glucose. A variety of agents was employed to act as hemolysin stabilizers. Hemolysin production was detected by lysis of sheep erythrocytes. Both iron and glucose were crucial in concentrations 5-7 micrograms/ml and 0.5-1% respectively. Bovine serum albumin-starch mixture acted as an excellent stabilizer. PMID- 2200869 TI - Conditioning by mitochondria and energy source of thermal death parameters in yeast. AB - Two strains of Saccharomyces cerevisiae of opposite mating type (a and alpha), with different resistance to thermal death, and their respective mitochondrial respiratory-deficient mutants (petites ap and alpha p) were used to prepare the following diploid strains: a alpha, a alpha p and ap alpha. Specific thermal death rates were determined at supramaximum temperatures for growth, under conditions of mitochondrial derepression (glycerol medium). Comparison of the entropies of activation of thermal death showed that diploids a alpha and ap alpha behaved like the more resistant haploid alpha, and diploid a alpha p like haploid a. In glucose medium strains alpha and a alpha became even more thermoresistant. The results favour the concept that thermal death determinants are located in the mitochondrial genome, and that mitochondria repressed cells repair thermal injuries more efficiently. PMID- 2200871 TI - [Elastic system fibers of healthy human gingiva]. AB - The elastic system fibers, i.e. oxytalan, elaunin and elastic fibers have respectively a fibrillar structure (oxytalan fibers), an amorphous structure (elastic fibers), or a mixed structure (elaunin fibers). The morphological distribution of these fibers is characterized by the presence of oxytalan, elaunin and elastic fibers in the upper medium and deep layers of gingival connective tissue. If the amorphous component is made up of elastin the microfibrillar component consist of structural glycoproteins containing aminoacids different of those found in elastin. Elastin is synthesized by gingival fibroblasts in the form of a precursor, tropoelastin, then disposed at the surface of the microfibrillar component and incorporated in the amorphous component. PMID- 2200872 TI - [Effect of insulin dependence on the periodontium: clinical study]. AB - The aim of this investigation was to study: the effect of insulin on the periodontal condition; the effect of insulin with age. 340 diabetics participated to this work. The examined teeth were the 16, 21, 24, 36, 41, 44. The indexes (Pl.I., G.I.), the depths of the pockets (upon these teeth); the quantity of gingival fluid (upon 21 and 24 only) were registrated. Statistically: the results showed: a better periodontal condition in the I.D.D. group, the I.D.D. are especially young patients less than 40 years, the insulin is active upon young population only, the periodontal destruction increases with age. PMID- 2200870 TI - DNA sequences from Saccharomycopsis fibuligera capable of autonomous replication in Saccharomyces cerevisiae. AB - A Sau3AI digest of total DNA from Saccharomycopsis fibuligera was cloned with the yeast-integrating plasmid YEp24 delta EcoRI and the capacity for autonomous replication (ARS) was assayed in yeast. From eighty clones, five mitoticaly unstable yeast transformants were picked up, recombinant plasmids from these clones were recovered with Escherichia coli, mapped, hybridized with total DNA of S. fibuligera and tested to mitotical stability in Saccharomyces cerevisiae. Experiments suggested the existence of DNA sequences from dimorphic Saccharomycopsis fibuligera with ARS activity in Saccharomyces cerevisiae. PMID- 2200874 TI - Gingival esthetics. AB - Achieving the most desirable gingival appearance enhances the esthetic result achieved with fixed prosthodontic restorations and is most often realized when gingival health is optimized before treatment and gingival trauma is minimized during treatment. Methods of optimizing gingival appearance by avoiding soft tissue contact are discussed as are factors considered important to maintaining good gingival appearance when subgingival margins are necessary. PMID- 2200873 TI - [Bacterial interaction in periodontal diseases]. AB - The aim of this review is to study the different interactions between human oral bacteria which, through specific mechanisms such as coaggregation, contribute to increase periodontal disease. PMID- 2200875 TI - A method for bonding extracted teeth to a cobalt-chrome prosthesis. PMID- 2200876 TI - Laboratory procedures for the one-clasp removable partial denture. PMID- 2200877 TI - Control of polymerization in the dispensing cartridge of automixing impression systems. AB - Continued polymerization of impression material stored in a previously used dispensing cartridge of an automixing impression system can lead to untoward results. This article describes a simple technique that will help overcome the problem. PMID- 2200878 TI - A standardized method for determination of crown margin fidelity. AB - Previous research on crown margin fidelity is reviewed and methods of measurement are compared and scrutinized. A standardized method for the determination of crown margin fidelity is introduced. A biologically oriented rationale is presented for analysis of the measurement parameters. This system places a strong emphasis on measuring factors that impact upon accumulation of plaque and the microbiologic environment around crowns, ultimately affecting gingival health. Crown samples were cemented on master dies and were embedded for sectioning buccolingually and mesiodistally. Photographs of margins with plastic overlays indicating emergence profiles were used to determine vertical and horizontal marginal discrepancies. Three observers measured seven crown systems for the vertical and horizontal marginal discrepancies of each crown system. The interobserver variance was 10 microns for the horizontal and 9 microns for the vertical marginal discrepancy. PMID- 2200879 TI - A 5-year longitudinal study of cantilevered fixed partial dentures compared with removable partial dentures in a geriatric population. AB - Prosthesis function and dental conditions were observed for 5 years in 27 elderly patients treated with mandibular cantilevered fixed partial dentures (FPDs) and in 26 elderly patients treated with distal-extension removal partial dentures (RPDs). All patients were treated with a complete upper denture. The patients were assigned randomly into two treatment groups that had the same composition with regard to sex, age, and distribution of teeth. The patients were under supervised oral hygiene and prosthodontic care. Clinical examination of prostheses, masticatory system, periodontal status, and caries was carried out yearly. Oral hygiene was good, and the periodontal status was maintained in both groups. Caries was observed six times more frequently in the RPD group than in the group with fixed restorations, however. Occlusal and functional conditions deteriorated in the RPD group only. Eight of 42 fixed partial dentures (19%) failed; of these, six were recemented with composite resin. Generally the need for dental and prosthetic follow-up treatment was more pronounced in the RPD group than in the FPD group. PMID- 2200880 TI - The longitudinal clinical effectiveness of osseointegrated dental implants: the Toronto Study. Part II: The prosthetic results. AB - Forty-six patients who had shown chronic maladaptive behavior in using complete dentures were treated with osseointegrated implant-supported prostheses. Forty patients needed mandibular treatment, three patients needed treatment in the maxillae, and three required treatment in both dental arches. At the most recent data collection (4 to 9 years after surgical placement of the implants), the 49 dental arches remained successfully treated with 44 implant-supported fixed partial dentures and five implant-supported overdentures. The efficacy of the osseointegration technique in maladaptive prosthetic patients is demonstrated in this descriptive study. PMID- 2200881 TI - Report of the Committee on Scientific Investigation of the American Academy of Restorative Dentistry. AB - The growth in the dental literature continues to escalate, as evidenced by the publication of at least 326 new books in 1988 and 1989 and more than 20 new journals in 1989. There still appears to be undue emphasis on quantity instead of quality of research. This proliferation in the literature poses ever increasing difficulties to this Committee in filtering out the articles that are of particular interest to the members of the Academy and identifying those that are most likely to have a major impact on dental practice and service. The subjects covered include periodontics, caries and preventive dentistry, craniomandibular disorders, occlusion, pulp biology, ceramics, and restorative dental materials. PMID- 2200882 TI - Statistical analysis of pharmacokinetic data. PMID- 2200883 TI - Structural identifiability of pharmacokinetic models--compartments and experimental design. PMID- 2200884 TI - Characterization of hepatitis delta antigen: specific binding to hepatitis delta virus RNA. AB - It has previously been shown that human hepatitis virus delta antigen has an RNA binding activity (Chang et al., J. Virol. 62:2403-2410, 1988). In the present study, the specificity of such an RNA-protein interaction was demonstrated by expressing various domains of the delta antigen in Escherichia coli as TrpE fusion proteins and testing their RNA-binding activities in a Northwestern protein-RNA immunoblot assay and RNA gel mobility shift assay. Hepatitis delta virus (HDV) RNA bound specifically to the delta antigen in the presence of an excess amount of unrelated RNAs and a relatively high salt concentration. Both genome- and antigenome-sense HDV RNAs and at least two different regions of HDV genomic RNA bound to the delta antigen. Surprisingly, these two different regions of HDV genomic RNA could compete with each other for delta antigen binding, although they do not have common nucleotide sequences. In contrast, this binding could not be competed with by other viral or cellular RNA. Since both the genomic and antigenomic HDV RNAs had strong intramolecular complementary sequences, these results suggest that the binding of delta antigen is probably specific for a secondary structure unique to the HDV RNA. By expressing different subdomains of the delta antigen, we found that the middle one-third of delta antigen was responsible for binding HDV RNA. Neither the N-terminal nor the C-terminal domain bound HDV RNA. Binding between the delta antigen and HDV RNA was also demonstrated within the HDV particles isolated from the plasma of a human delta hepatitis patient. This in vivo binding resisted treatment with 0.1% sodium dodecyl sulfate and 0.5% Nonidet P-40. In addition, we showed that the antiserum from a human patient with delta hepatitis reacted with all three subdomains of the delta antigen, indicating that all of the domains are immunogenic in vivo. These studies demonstrated the specific interaction between delta antigen and HDV RNA. PMID- 2200885 TI - Direct and cytokine-mediated activation of protein kinase C induces human immunodeficiency virus expression in chronically infected promonocytic cells. AB - The chronically infected promonocytic clone U1 expresses low-to-undetectable constitutive levels of human immunodeficiency virus (HIV). Virus replication in these cells can be increased up to 25-fold by phorbol esters (phorbol-12 myristate-13-acetate), recombinant cytokines such as tumor necrosis factor-alpha, and cytokine-enriched mononuclear cell supernatants. We have tested specific activators of protein kinases (PK) and PK inhibitors (isoquinolinesulfonamide derivatives), as well as calcium-mobilizing agents, for their effect on constitutive and induced virus expression in U1 cells. Virus expression was measured by reverse transcriptase, Western blot, and nuclear run-on analysis. Activation of PKC by 1-oleyl,2-acetylglycerol, a synthetic analog of the natural ligand 1,2-diacylglycerol, and bryostatin 1 (a recently described specific PKC activator) resulted in a two- to eightfold increase in virus production. In contrast, activators of cyclic-nucleotide-dependent PKs were not effective in inducing virus expression. PK inhibitors were tested for their effect on HIV upregulation by cytokines and other inducing agents. The isoquinolinesulfonamide derivative H7, a potent inhibitor of PKC activation, effectively blocked (70 to 90%) HIV induction by cytokines and phorbol-12-myristate-13-acetate. The derivative HA1004, which is more selective for cyclic-nucleotide-dependent kinases, did not suppress viral induction. In addition, increases in intracellular calcium levels dramatically enhanced HIV production induced by both specific PKC activators and cytokines. These results indicate that activation of PKC is a common pathway involved in the upregulation of HIV expression in chronically infected cells stimulated by cytokines and other inducing agents. PMID- 2200886 TI - Function of Semliki Forest virus E3 peptide in virus assembly: replacement of E3 with an artificial signal peptide abolishes spike heterodimerization and surface expression of E1. AB - The Semliki Forest virus spike glycoproteins E1 and p62 form a heterodimeric complex in the endoplasmic reticulum (ER) and are transported as such to the cell surface. In the mature virus particle, the heterodimeric association of E1 and E2 (the cleavage product of p62) is maintained, but as a more labile and acid sensitive oligomer than the E1-p62 complex. The E3 peptide forms the N-terminal part of the p62 precursor and carries the signal for the translocation of p62 into the lumen of the ER. The question of whether E3 is also important in the formation and stabilization of the E1-p62 heterodimer has been addressed here with the aid of an E3 deletion mutant cDNA. In this construct, the entire E3 was replaced with a cleavable, artificial signal sequence which preserved the membrane topology of an authentic E2. The E3 deletion, when expressed via a recombinant vaccinia virus, abolished heterodimerization of the spike proteins. It also resulted in the complete retention of E1 in the ER and almost total inhibition of E2 transport to the plasma membrane. The oligomerization and transport defect of E1 expressed from the E3 deletion mutant could be complemented with a wild-type p62 provided from a separate coding unit in double infections. These results point to a central role of E3 in complex formation and transport of the viral structural components to the site of budding. In conjunction with earlier work (M. Lobigs and H. Garoff, J. Virol. 64:1233-1240, 1990; J. Wahlberg, W. A. M. Boere, and H. Garoff, J. Virol. 63:4991-4997, 1989), the data support a model of spike protein oligomerization control of Semliki Forest virus assembly and disassembly which may be mediated by the presence of E3 in the uncleaved p62 precursor and release of E3 after cleavage. PMID- 2200887 TI - Structural role of the matrix protein of type D retroviruses in gag polyprotein stability and capsid assembly. AB - To obtain a better understanding of the role of the gag gene-encoded matrix (MA) protein in the assembly and maturation of type D retroviruses, we have made five mutants with specific in-frame deletions within the p10-coding region by the use of oligonucleotide-directed mutagenesis. The changes in the Gag polyprotein made by these mutations resulted in almost identical phenotypes. In cells expressing mutant genomes, the mutant Gag polyproteins were synthesized and modified with myristic acid in a normal manner. However, they were so unstable that the bulk of the newly synthesized polyproteins was degraded within 1 h without being processed into mature structural polypeptides. In contrast, wild-type polyproteins have a processing half-life of 3.0 to 3.5 h. The mutant Gag polyproteins were assembled with very low efficiency into capsids in the cytoplasm of the mutant-infected cells. Moreover, the few capsids that formed were neither released from nor accumulated in the cells. These results suggest that the matrix protein plays an important role in guiding the correct folding of the Gag polyprotein, which is presumably crucial for both stabilizing the molecule and facilitating the intermolecular interactions that occur during assembly of immature capsids. PMID- 2200888 TI - Function of the human immunodeficiency virus types 1 and 2 Rev proteins is dependent on their ability to interact with a structured region present in env gene mRNA. AB - The interaction of the human immunodeficiency virus type 1 (HIV-1) Rev protein with a structured region in env mRNA (the Rev-responsive element [RRE]) mediates the export of structural mRNAs from the nucleus to the cytoplasm. We demonstrated that unlike HIV-1 Rev, which functions with both the HIV-1 and HIV-2 RREs, HIV-2 Rev functions only with the HIV-2 RRE. Rev-RRE binding studies suggested that the lack of nonreciprocal complementation stems from the inability of HIV-2 Rev to interact with HIV-1 RRE RNA. Maintenance of RNA secondary structure, rather than the primary nucleotide sequence, appeared to be the major determinant for interaction of both HIV-1 and HIV-2 Rev with the HIV-2 RRE. Moreover, the binding domain of the HIV-2 RRE recognized by HIV-1 Rev was dissimilar to the binding domain of the HIV-1 RRE, in terms of both secondary structure and primary nucleotide sequence. Our results support the hypothesis that function of HIV Rev proteins and possibly the functionally similar Rex proteins encoded by the human T-cell leukemia viruses (HTLVs) HTLV-I and HTLV-II is controlled by the presence of RNA secondary structure generated within the RRE RNA. PMID- 2200889 TI - Macrophage-tropic strains of human immunodeficiency virus type 1 utilize the CD4 receptor. AB - To characterize the role of CD4 in human immunodeficiency virus type 1 (HIV-1) infection of macrophages, we examined the expression of CD4 by primary human monocyte-derived macrophages and studied the effect of recombinant soluble CD4 and anti-CD4 monoclonal antibodies on HIV-1 infection of these cells. Immunofluorescence and Western blot (immunoblot) studies demonstrated that both monocytes and macrophages display low levels of surface CD4, which is identical in mobility to CD4 in lymphocytes. Recombinant soluble CD4 and the anti-CD4 monoclonal antibody Leu3a blocked infection of macrophages by three different macrophage-tropic HIV isolates, and the cytopathic effects of HIV-1 infection were similarly prevented. Dose-response experiments using a prototype isolate which replicates in both macrophages and T lymphocytes showed that recombinant soluble CD4 inhibited infection of macrophages more efficiently than in lymphocytes. These results indicate that CD4 is the dominant entry pathway for HIV-1 infection of macrophages. In addition, recombinant soluble CD4 effectively blocks HIV-1 infection by a variety of macrophage-tropic strains and thus has the potential for therapeutic use in macrophage-dependent pathogenesis in HIV disease. PMID- 2200890 TI - Human chromosome 12 encodes a species-specific factor which increases human immunodeficiency virus type 1 tat-mediated trans activation in rodent cells. AB - The human immunodeficiency virus type 1 (HIV-1) tat protein functions at a much lower level in rodent cells than in human cells. This species-specific difference in trans activation appears to be due to the lack of a functional homolog of a human cofactor for tat in rodent cells. Using HIV-1 long terminal repeat-driven human growth hormone as a reporter plasmid, we found that the tat-mediated trans activation functions at a level 5- to 20-fold lower in rodent cells than in human cells. Stable rodent-human hybrid cells containing only human chromosome 12 support a dramatically higher degree of trans activation. Thus, human chromosome 12 encodes a species-specific HIV-1 tat cofactor which, at least partially, restores high levels of tat-mediated trans activation. Chromosome 6 also appears to provide an additional factor which enhances HIV-1 tat-mediated trans activation in murine cells. PMID- 2200891 TI - Preleukemic hematopoietic hyperplasia induced by Moloney murine leukemia virus is an indirect consequence of viral infection. AB - We previously showed that neonatal mice inoculated with Moloney murine leukemia virus (M-MuLV) exhibit a preleukemic state characterized by splenomegaly and increased numbers of hematopoietic progenitors. An M-MuLV variant with greatly reduced leukemogenic potential, Mo+PyF101 M-MuLV, does not generally induce this preleukemic state. In order to investigate the mechanism involved in M-MuLV induction of preleukemic hyperplasia, we tested the CFU-mixed myeloid and erythroid (CFUmix) from M-MuLV- and Mo+PyF101 M-MuLV-inoculated mice for the presence of virus by antibody staining and for the release of infectious virus. The majority of CFUmix colonies from both M-MuLV- and Mo+PyF101 M-MuLV-inoculated mice contained infectious virus even though M-MuLV-inoculated mice showed elevated levels of CFUmix while the Mo+PyF101 M-MuLV-inoculated mice did not. This indicates that direct infection of hematopoietic progenitors was not sufficient to induce hyperplasia. Rather, hematopoietic hyperplasia may result indirectly from infection of some other cell type. PMID- 2200892 TI - Silent myocardial ischemia. Is the person or the event silent? AB - The symptoms of organic disease vary widely among patients with the same tissue abnormality, because the experience of a symptom is shaped by the patient's perceptual and cognitive style. Thus, the relationship between myocardial ischemia and chest pain is variable in that many patients experience pain without ischemia and many others exhibit ischemia without pain-termed "silent" or "asymptomatic ischemia." Although the nature of the ischemic event may be important in determining the degree of associated pain, we suggest more study of the individual who perceives the event. Myocardial ischemia may not generate a spontaneous report of chest pain because the patient is generally hyposensitive to visceral sensation; because he or she is coping with the threat of heart disease by denying the evidence of it--ie, denying the pain to deny the disease; or because the patient misunderstands the cause and significance of a vague or ambiguous cardiac sensation, normalizing the symptom and misattributing it to a nonpathologic cause. PMID- 2200893 TI - Corot's 'gout' and a 'gipsy' girl. AB - Representations of rheumatic disease in art provide insight into artistic expression, help us understand the evolution and perhaps the etiology of rheumatic diseases, and remind us of great contributions by artists in adverse circumstances. We noted hand deformities characteristic of inflammatory arthritis in Jean-Baptiste-Camille Corot's Gipsy Girl With Mandolin (1870 to 1875), National Gallery of Art, Washington, DC. Corot suffered with what probably was gout beginning in 1866. We are unaware that arthritis has been observed in Corot's subjects or that Corot's depiction of arthritis has been appreciated from the perspective of his own rheumatic disease. Examination of other Corot portraits identifies some with blurred hand details consistent with the artist's style and the remainder with normal hands. These observations suggest that the artist portrayed specific anatomic abnormalities in the "Gipsy Girl's" hand, indicating familiarity with inflammatory arthritis. It is speculative whether this was Corot's own or the model's arthritis; we favor the interpretation that Corot's gout was reflected in this particular work. We thus add a new perspective to Corot's Gipsy Girl With Mandolin-a subject with arthritis, a painter knowledgeable about arthritis, and a painting that therefore might be understood at least in part from an appreciation of the artist's specific illness. PMID- 2200894 TI - Frequency of adverse reactions to influenza vaccine in the elderly. A randomized, placebo-controlled trial. AB - Concern about side effects constitutes a major deterrent to patient compliance with influenza vaccination, yet there is a paucity of data about the occurrence of adverse reactions in the population targeted for immunization. We conducted a randomized, double-blind, crossover trial to compare the frequency of adverse reactions following administration of 1988-1989 trivalent split-antigen influenza vaccine and saline placebo. Outpatient veterans 65 years of age or over (n = 336) were recruited by mail and were randomly assigned to receive vaccine followed 2 weeks later by placebo injection or placebo followed 2 weeks later by vaccine. There was no significant difference between influenza vaccine and placebo with respect ot the proportion of subjects reporting disability or systemic symptoms. PMID- 2200895 TI - Dreams, dollars, and deeds. The sacred fire and health access America. PMID- 2200896 TI - [Does induction with midazolam decrease stress response during anesthesia?]. AB - The effects of midazolam on stress response during surgery compared with thiamylal were studied. Twelve patients were divided into 2 groups at random; midazolam group and thiamylal group. Anesthesia was induced with midazolam 0.2 mg.kg-1 or thiamylal 4 mg.kg-1 in each group, and maintained with O2 2 l.min-1, N2O 4 l.min-1 and enflurane. The plasma concentration of catecholamine was measured at preinduction, 10, 30, 60, 120 and 180 minutes after intubation. No significant differences were seen between 2 groups in plasma concentration of catecholamine. In midazolam group, plasma concentration of epinephrine decreased significantly 10 minutes after intubation as compared with preinduction level. The plasma concentration of norepinephrine in midazolam group tended to decrease. In thiamylal group, plasma concentration of norepinephrine tended to increase and increased significantly at 120 and 180 minutes after intubation as compared with preinduction level. These results suggest that induction with midazolam suppresses stress response during anesthetic induction and surgery more intensely than induction with thiamylal. PMID- 2200897 TI - [Hypertension and prostanoids--the etiology and its implications for treatment]. PMID- 2200898 TI - [Aspects of new drug development]. PMID- 2200899 TI - [Recent advances in positron emission tomography]. PMID- 2200900 TI - [Autoimmune chylomicronemia--pathogenesis and pathophysiology]. PMID- 2200901 TI - [Recent studies of cerebral metabolism by nuclear magnetic resonance spectroscopy]. PMID- 2200902 TI - Role of delayed type hypersensitivity responses in protection during chronic Plasmodium berghei infection as evidenced by homing of radiolabelled bone marrow cells and contact sensitivity. AB - A comparative study of specific and non-specific immunosuppression has been carried out in acute and chronic Plasmodium berghei infected mice in an in vivo system. In our previous studies, immunosuppression during acute P. berghei infection was attributed to T lymphocytes when we studied modulation of blastogenic response of lymphocytes in an in vitro system. In the present study, delayed type hypersensitivity (DTH) was evident from the homing of radiolabelled bone marrow cells into the delayed lesions of antigen challenged foot pads during chronic infection. This response was suppressed during acute infection especially in early stages. A greater concentration of bone marrow cells in the liver and spleen occurred during chronic infection in comparison with acute infection. When radiolabelled bone marrow cells from infected mice were injected into the normal mice previously given malaria antigen in foot pads, no significant change in homing pattern in liver, spleen or foot pads was observed. Contact sensitivity to picryl chloride was suppressed during acute infection, but was intact during chronic infection. Since these responses are mediated by T lymphocytes, significance of these responses is discussed. PMID- 2200903 TI - Modulation of c-myc gene expression by extracellular stimuli in rat hepatoma cells. AB - Modulation of c-myc gene expression by extracellular stimuli in H4IIE rat hepatoma cells was investigated by Northern blot analysis. Treatment of these cells with phorbol 12-O-tetradecanoate 13-acetate (TPA), insulin and concanavalin A (Con A) resulted in transient accumulation of c-myc transcripts within 2 hours. The induction of c-myc mRNA was dose dependent with similar responses for all three agents. The maximally induced c-myc mRNA levels varied from 5- to 15-fold of the control. Treatment with cycloheximide (10 micrograms/ml) and H7, a protein kinase C inhibitor (20 microM), inhibited this induction, suggesting that c-myc induction by these agents requires protein synthesis and protein kinase C activation. PMID- 2200904 TI - [Endoscopic ultrasonography for assessing the horizontal spread of invasive gastric cancer]. AB - The subjects were 64 cases of gastric cancer. In all 64 cases, resected specimens (formalin fixed) were subjected to endoscopic ultrasonographic examination by the water immersion method in order to assess the horizontal spread of the invasive gastric cancer. Ultrasonographic findings were compared with the histopathological findings of resected specimens. The tumor which invaded the submucosa or deeper layers was visualized as low echogenicity region in the third layer (corresponding to the submucosa) or deeper layers. The horizontal spread of the low echogenicity region represented that of the tumor or the associated fibrosis, but not the tumor itself. In the cases showing echo patterns which were characteristic of the peptic ulceration in the tumor focus (Type II-1, II-2, UL), the horizontal spread of cancer invasion in the submucosal layer or deeper layers (L Ca) was smaller than that of low echogenicity region depicted by ultrasonography (L U). In the other (Type II-3, III, A, B) cases, L Ca was almost comparable to L U. PMID- 2200905 TI - [Three cases of recurrent ischemic colitis]. PMID- 2200906 TI - [A case of large colon cavernous hemangioma in childhood]. PMID- 2200907 TI - [A case of giant mesosigmoid leiomyosarcoma--review of Japanese literature]. PMID- 2200908 TI - [Brain aging and Parkinson's disease]. PMID- 2200909 TI - [Decubitus]. AB - Since decubitus, one of the common lesions, is not yet fully under medical control, it still offers serious problems. The incidence of this lesion once comprised about 12% of the patients hospitalized in a geriatric institution, and was responsible for the development of sepsis in about 20% of those cases. Although the incidence of this lesion has been declining, it still debilitates many geriatric patients, especially with neurological or malignant diseases. Care being necessary to disperse the pressure on the skin adjacent to the bone, many devices have been invented. The air-fluidized bed is especially effective in preventing and alleviating decubitus. However, a simple device utilizing polyvinyl sponge plates is worthy to try from the standpoint of cost-performance. Several surgical reparative manoeuvres as well as newly developed medicines, such as prostaglandin E1, etc. now promote favourable outcomes. However, the importance of basic preventive care, such as postural change with massage, local hygiene, nutrition, etc. cannot be ignored. PMID- 2200910 TI - [Urinary incontinence in the aged]. AB - Following the recent increase in the aged population, an increase in the number of cases of urinary incontinence among aged people can be anticipated. Considering the relative decrease of care-givers such as cohabitating family and increase of the cost of incontinence care, a social and national economic problem might be arise in near future. Therefore rapid steps to cope with this situation are necessary. Urinary incontinence of the aged has been mainly considered to be the problem for management and have been avoided by medical professionals until recently. Urinary incontinence is not only a problem of only aging, but generally is caused by some disease, therefore medical care might cure the incontinence or make the management of it easier. However, considering the increase in the number of elderly aged urinary incontinence patients, the number of incontinence-care professionals is very small. Help from the general practitioners is indispensable. Therefore this speech was drafted with the wish that the audiences, manly medical and geriatric doctors who usually are in contact with aged patients, may understand and become familiar with urinary incontinence of the elderly. This paper covered the physiology of urination especially in relation to the nervous system, abnormal bladder and urethral function found in urodynamic tests of elderly apparently normal persons, pathophysiological mechanism of urinary incontinence of aged people, urinary incontinence evoked as a side effect of some drugs. In order to assess and manage elderly urinary incontinence better, we must be able to recognize often there are two or more simultaneous basic underlying causes and how combinations of these cause create multifactorial mixed types of urinary incontinence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2200911 TI - [Oral aging and loss of teeth]. AB - The human oral mucosa atrophies with aging, and at the same time, loss of teeth occurs and the muscles involved in mastication weaken, leading to masticatory hypofunction. The loss of teeth in animal is serious in that it leads to death. For humans, however, dental prosthesis may aim at functional recovery. From the viewpoint of oral functional recovery, it is important to have a firm grasp of the change in the oral environment with aging. Elderly patients who complain of dry mouth may often have glossodynia, stomatitis, dysgeusia, prosthetic disorder, etc. Although atrophy of the salivary gland is mainly responsible for these disturbances, influences of complications and/or medications cannot be ignored. Secretory immunoglobulin A (sIgA) secretion in the saliva of elderly cases showed a concentration comparable to that of young subjects in their twenties and was considered to be satisfactory from the view-point of oral infection control. On the other hand, plate prosthetic wearers may have high incidence of oral candidiasis, so that in case of loss of teeth, prostheses with so-called implant dentures using artificial dental implants are regarded as physiologically preferable to conventional plate denture. PMID- 2200912 TI - [Free radicals and lipid peroxides--their relation to atherogenesis]. PMID- 2200913 TI - [Free radicals and diabetes mellitus]. AB - There is direct evidence that there is an increase of concentration of oxidizing species and oxidized products in plasma of human diabetics. The extent of this increase seems to reflect a predilection to diabetic damage. 1. A high concentration of lipid hydroperoxide in plasma was observed in diabetic patients and it's levels correlated well with the degree of diabetic nephropathy. 2. Lipid peroxide causes membrane injury of endothelial cells. The addition of anti oxidant inhibited cell injury markedly. 3. Malondialdehyde and protein (lysin residual or low density lipoprotein) made conjugates to change the antigenicity. This results shows the possibility that atherosclerosis as diabetic complication may be caused by immunological reactions with modified proteins for example, oxidized LDL and so on. 4. SOD activity in erythrocytes of diabetic patient was extremely decreased compared with non diabetics, but no difference was observed by the ELISA method with monoclonal antibody. Glycosylation had been expected to occur in various kinds of proteins. The inactivation of SOD may be caused by non enzymatic glycosylation, because negative correlation was observed between the activity of SOD and GHb in erythrocytes. This inactivation of SOD may play an important role in the pathogenesis of diabetic complications. From these results, it was suggested that both free radical reactions and non enzymatic glycosylation may play important roles not only in the development of diabetes but also in its complications. PMID- 2200914 TI - [Free radicals in digestive diseases]. AB - Free radicals have recently been implicated in a number of biochemical and chemical reactions in the body. Lipid peroxidation induced by free radical reaction is believed to be one of the major causes of cell damage and injuries in cell membranes. In recent years, reports have appeared citing the contribution of free radicals and active oxygen species in the etiology of various digestive diseases. For example, gastric mucosal injuries and the increases in thiobarbituric acid-reactive substances in the gastric mucosa induced by ischemia or ischemia/reperfusion were significantly inhibited by treatment with superoxide dismutase and catalase. It has been suggested that superoxide radical or hydroxyl radical may be the major oxygen radicals contributing to ischemia or ischemia/reperfusion injury in the stomach, small intestine, and liver. There reactive species can attack and damage important biological molecules. Within cellular membranes, hydroxyl radical can initiate a free radical chain reaction known as lipid peroxidation, in which polyunsaturated fatty acids are broken down into water soluble products and toxic lipid peroxides are produced with the consequent destruction of membrane integrity. The major source of active oxygen species produced after ischemia or ischemia/reperfusion seems to be the enzymatic xanthine oxidase and activated polymorphonuclear leukocytes (PMN). In the large intestine which has little activity in xanthine oxidase, PMNs are a more important source of active oxygen species and play a role in the pathogenesis of the inflammatory bowel diseases. The above information suggests that oxygen derived free radicals are involved in the fundamental mechanism of tissue injury in various disorders of the digestive system. PMID- 2200915 TI - [Oxygen radicals in cerebrovascular diseases]. PMID- 2200916 TI - [Free radicals and degenerative diseases of the nervous system]. AB - Degenerative diseases of the nervous system which are considered to be related to free radicals are Parkinson's disease and Alzheimer-type dementia (ATD). Parkinson's disease is characterized by appearance of Leyw's body and degeneration of nigrostriatal dopaminergic system. But the most fundamental cause of this disease remains still unknown. The fact that H2O2 is formed in the process of oxidative deamination of catecholamines and some substances which can cause Parkinsonism in animal experiments also produce active oxygen in the metabolic processes suggest the important role of free radicals in the pathogenesis of Parkinson's disease. We recently observed that addition of DOPA and Fe3(+)-ADP complex to the microsomal phospholipid system produced lipid peroxides without participation of active oxygen. Neurons cultured in vitro also decreased significantly with addition of DOPA and Fe3(+)-ADP complex and this harmful effect was prevented by desferoxamine (potent Fe chelating agent) or alpha-tocopherol (antioxidant). These results may suggest that lipid peroxidation can occur by interaction of naturally existing substances in the dopaminergic system and induce cell damage. As regards ATD, there is still no definite evidence to support the implication of free radicals in its pathogenesis. However, there are reports that lipid peroxides increase significantly in the brains of patients with ATD. Moreover, recent advances in the study of amyloid in the senile plaque revealed close relationship of ATD to chromosome 21.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2200917 TI - [The role of oxygen free radicals in the aging of the brain]. AB - The role of free radicals, particularly of oxygen free radicals, in the aging mechanism is reviewed including our own data. The TBA-reactive product level has been shown to increase with aging. Lipid-peroxidation is stimulated by hydroxyl radical and singlet oxygen. Therefore, the metabolism of oxygen free radicals is an important subject of the investigation. The activity of superoxide dismutase has been reported to be either unchanged or increased with age. The activity of glutathione peroxidase has been reported to increase with aging by several authors. These results have been interpreted as suggesting the increased formation of oxygen free radicals with aging with subsequent reactive increase in these enzyme activities. However, the question whether the formation of oxygen free radicals is indeed increased in aging tissues or not has not been clarified yet because of the technical difficulties in measuring free radicals. Increases in TBA-reactive product level was demonstrated in the frontal lobe, the temporal lobe, the septal area, the hippocampus, the striatum and the substantia nigra in aging rats. In these areas, a small but significant decrease in the activity of superoxide dismutase was noted. On the other hand, in the areas where the activity of superoxide dismutase was increased with aging, the level of TBA reactive products did not increase. Further studies are needed to elucidate the role of oxygen free radicals in the aging process. PMID- 2200918 TI - Pharmacological studies on (4S)-1-methyl-3-[(2S)-2-[N-((1S)-1-ethoxycarbonyl-3 phenylpropyl)amino] propionyl]-2-oxo-imidazolidine-4-carboxylic acid hydrochloride (TA-6366), a new ACE inhibitor: I. ACE inhibitory and anti hypertensive activities. AB - TA-6366 and its active metabolite 6366A inhibited swine renal angiotensin converting enzyme (ACE) activity with IC50s of 9900 and 2.6 nM, respectively. TA 6366 (0.05-0.5 mg/kg, p.o.) inhibited the angiotensin I (AT-I)-induced pressor response in rats. 6366A augmented bradykinin (BK)-induced contraction of guinea pig ileum more potently than captopril. However, when the augmentation on BK induced hypotension in rats was used as an indicator, TA-6366 was less active than captopril. TA-6366 increased plasma renin activity and plasma AT-I concentration. Oral administration of TA-6366 lowered the blood pressure in two kidney one-clip renal hypertensive rats at 0.5 to 2 mg/kg and in spontaneously hypertensive rats (SHRs) at 2 to 10 mg/kg. The antihypertensive effect of TA-6366 was approximately 5 times more potent than that of captopril and almost as potent as that of enalapril. In SHRs, the antihypertensive action of TA-6366 was intensified in potency when administered repeatedly. The duration of action was longer than those of captopril and enalapril. However, TA-6366 had no substantial effect on the blood pressure in DOCA/saline hypertensive rats. These results indicate that TA-6366 is a potent and long lasting antihypertensive agent and that its antihypertensive action is attributable to the inhibition of ACE. PMID- 2200919 TI - Demonstration of kinin-release in the peritoneal exudate of kaolin-induced writhing in mice. AB - Using a bradykinin enzyme immunoassay, we measured the amount of kinin in the peritoneal washings of mice with the kaolin-induced writhing reaction. Simultaneous treatment with captopril, a kininase II inhibitor, significantly increased the kinin level at 1 min after kaolin injection. Soybean trypsin inhibitor injected simultaneously with kaolin almost completely suppressed the kinin level at 1 min with or without treatment of captopril. These results suggest that kinin is released through activation of the plasma kallikrein-kinin system by kaolin, and that kinin could be a main mediator for the writhing reaction. PMID- 2200920 TI - The arrhythmogenic action of endothelin in rats. AB - Endothelin (ET) was administered into the coronary ostia at doses of 0.1-1 microgram/kg in anesthetized rats. The ST segment was depressed at doses below 0.5 microgram/kg and was transiently elevated at 1 microgram/kg. Ventricular arrhythmias developed at doses above 0.5 microgram/kg. The arrhythmias that developed at 1 microgram/kg were precipitated into ventricular fibrillation. At the time when the arrhythmias developed, the ischemic changes had already subsided. These results suggest that ET may have an arrhythmogenic action, which is not solely attributable to myocardial ischemia. PMID- 2200921 TI - Antihypertensive effect of CS-905, a novel dihydropyridine calcium blocker, in conscious hypertensive dogs. AB - CS-905, (+-)-3-(1-diphenylmethylazetidin-3-yl)5-isopropyl 2-amino-1,4-dihydro-6 methyl-4-(m-nitrophenyl)-3,5-pyridine-dicarboxy lat e, is a novel dihydropyridine calcium blocker. Both CS-905 and nicardipine, when administered orally, produced a dose-dependent fall of blood pressure in conscious perinephritic hypertensive dogs. Unlike the hypotensive effect of nicardipine, that of CS-905 has a gradual onset and is long-lasting, with little increase in the heart rate and plasma renin activity (PRA). The lack of both tachycardia and increase of PRA is probably mostly due to the slow onset of antihypertensive action following CS 905. PMID- 2200922 TI - [Ruptured congenital aneurysm of the sinus of valsalva in the aged]. AB - Ruptured aneurysm of the sinus of Valsalva is a rare cardiac lesion. A ruptured aneurysm of the sinus of Valsalva in the right ventricle of a 64-year-old man was successfully repaired. The patient was admitted to the hospital with high fever and chest oppression. Diagnosis was made by two dimensional echocardiography, cardiac catheterization, and cardiac angiography. An aortotomy, main pulmonary arteriotomy, and right ventriculotomy were performed. There was no VSD, and the aneurysm originated from the right coronary sinus, rupturing into the right ventricle inlet portion. The ruptured aneurysm of the sinus of Valsalva was closed with a Dacron patch from inside the aorta. He is doing well after surgery. There was no heart murmur. CTR decreased and pulmonary blood flow fell to a normal value. As far as we know, this patient is the second oldest patient in Japan with surgical repair. PMID- 2200923 TI - Emergency nurse and disaster specialist--Starre Ann Haney. PMID- 2200924 TI - Effects of ACE inhibition in normotensive patients with chronic glomerular disease and normal renal function. AB - A double-blind, placebo-controlled study was carried out to assess the effects of a three-month treatment with a new ACE inhibitor, Benazepril (BNZ), on systemic and renal hemodynamics, and urine protein excretion, in 20 patients with chronic glomerulonephritis, normal blood pressure (130/83 +/- 16/10 mm Hg), and normal renal function (creatine clearance 106 +/- 25 ml/min). Treatments with placebo or BNZ were assigned randomly. A wide range of proteinuria lowering effect was observed in overall population (from 1 to 84%, average 34%). Following the arbitrary level of a 30% reduction, two well-matched subgroups (10 patients for each one) were obtained: "good responders" (average decrease 51%), and "poor responders" (average decrease 17%). The main distinctive feature between the two groups was a higher plasma renin activity level in good than in poor responders. A positive correlation between the fall in proteinuria and blood pressure was found. Although the decrease in blood pressure seems to represent the major factor in determining the reduction in proteinuria, a multiple correlation analysis showed that the most prominent role (71%) was attributable to the combined decrease in blood pressure and filtration fraction, and then also to the efferent arteriole dilatation. Our conclusion is that ACE inhibitors are capable of also reducing proteinuria in patients with renal disease with normal blood pressure, the effect being more pronounced in those exhibiting humoral, systemic and renal hemodynamic patterns, indicating a greater activity of circulating and renal renin angiotensin system. PMID- 2200925 TI - Measurement of renal function in chronic renal disease. PMID- 2200926 TI - Establishment of an esophageal squamous cell carcinoma tumor line and development of serum squamous cell carcinoma-related antigen in athymic nude mice. AB - A serially transplantable tumor line (IMEs-1) derived from human esophageal squamous cell carcinoma (SCC) of a 71-year-old female was established in nude mice. The histology of IMEs-1 closely resembled that of the original tumor and tumor doubling time was 3.2 days. Production of SCC-related antigen (SCCRA) and carcinoembryonic antigen (CEA) in the serum of tumor-bearing mice was observed. To evaluate the usefulness of SCCRA for esophageal cancer, the relationship between the serum levels of SCCRA and tumor burden in athymic nude mice bearing IMEs-1 was studied. The mean serum levels of SCCRA, as determined by radioimmunoassay, gradually rose in direct proportion to the tumor growth gauged by tumor volume. However, the serum levels of CEA did not increase until the last few weeks of the assay. These results suggest the possibility of using SCCRA as a tumor marker for esophageal SCC. In addition, this nude mouse assay system will provide a theoretical model to study the usefulness of SCCRA. PMID- 2200927 TI - Multicentric adult secretory breast carcinoma: DNA flow cytometric findings, prognostic features, and review of the world literature. AB - A case of multicentric secretory breast carcinoma in a 39-year-old white female is described. Mammograms, DNA analysis, touch preparation cytology, and positive estrogen receptors are reported for the first time in this rare favorable mammary carcinoma. A review of the 33 reported cases with follow-up in adult females, including the present case, has revealed lymph node metastases in nine (27%), recurrence in four (12%), and distant metastases leading to death in two cases (6%). In patients treated with less than simple mastectomy there has been local recurrence in 4 (33%) of 12 cases and in three of the four cases (75%) greater than or equal to 2.0 cm. Increased size and lack of gross circumscription of the neoplasm and presentation in the adult age group appear to identify cases with an increased risk of disease progression. In patients over 20 years old, especially with neoplasms greater than 2 cm in diameter, modified radical mastectomy has to date achieved the most favorable outcome. Minimal experience (two cases) is available regarding treatment with limited surgery and radiation therapy, and there is no available data regarding possible benefit from adjuvant chemotherapy. PMID- 2200928 TI - Pulmonary coin lesions caused by Dirofilaria immitis. AB - The dog heartworm Dirofilaria immitis has been diagnosed by thoracotomy as the etiology of neoplastic-appearing nodules in two patients in the Peoria, Illinois area. This brings the total number of reported cases of human pulmonary dirofilariasis to approximately 81 in the United States. The major concern of this benign disease is that in making the diagnosis the patients undergo the risk of surgery because of the presumed preoperative diagnosis of cancer. Greater awareness of this disease is needed as the geographic distribution of human pulmonary dirofilariasis expands in this country. PMID- 2200929 TI - Cellular concentrations of enzymes and their substrates. AB - The activity of crude and pure enzyme preparations as well as the molecular weight of these enzymes were obtained from the literature for several organisms. From these data enzyme concentrations were calculated and compared to the concentration(s) of their substrates in the same organism. The data are expressed as molar ratios of metabolite concentration to enzyme site concentration. Of the 140 ratios calculated, 88% were one or greater, indicating that in general substrates exceed their cognate enzyme concentrations. Of the 17 cases where enzyme exceeds metabolite concentration, 16 were in glycolysis. The data in general justify the use of enzyme kinetic mechanisms determined in vitro in the construction of dynamic models which simulate in vivo metabolism. PMID- 2200930 TI - Koinophilia groups sexual creatures into species, promotes stasis, and stabilizes social behaviour. AB - In a population whose members' genomes are subject to degradation by random mutations, the heritable vigour of the most common phenotypes is unquestionable (though not necessarily optimal), and that of fringe individuals is always suspect. Natural selection will therefore support the evolution of an affinity for modal mates (i.e. koinophilia). The population's genetic make-up can then not readily be invaded by non-cryptic mutations. This imposes considerable phenotypic conservatism on sexually reproducing creatures, and inexorably canalizes them into sexually isolated, phenotypically distinct species. The model predicts, and the empiric data confirms, that the phenotypic gaps between largely monomorphic sexual species do not characterize the taxonomy of longstanding apomicts, where variation below the genus level is often continuous. The bias against the propagation of all forms of phenotypic novelty and non-conformity stabilizes social animals against selfish mutants, thus removing the barriers to the evolution of "group adaptations". PMID- 2200931 TI - The effective treatment of postpericardiotomy syndrome after cardiac operations. A randomized placebo-controlled trial. AB - Although the postpericardiotomy syndrome is a common complication of cardiac operations, the most effective drug regimen for the treatment of this condition has not been established. The present study was designed to evaluate the effectiveness of nonsteroidal antiinflammatory drugs (NSAIDs) in the treatment of postpericardiotomy syndrome, in a double-blind, placebo-controlled randomized trial with a 10-day course of ibuprofen or indomethacin. Of 1019 adult patients undergoing cardiac operations during a 14-month period, a diagnosis of postpericardiotomy syndrome was made in 187, and 149 were enrolled in the study. Diagnosis was based on the presence of at least two of the following: fever, anterior chest pain, and friction rub. Drug efficacy was defined as the resolution of at least two of these criteria within 48 hours of drug initiation. Ibuprofen and indomethacin were 90.2% and 88.7% effective, respectively, and both were significantly more effective than placebo (62.5%, p = 0.003). The occurrence of side effects, including nausea, vomiting, renal failure, and fluid retention, was low in all groups (13.1% for ibuprofen, 16.1% for indomethacin, and 16.7% for placebo [p = not significant). Length of hospital stay, incidence of ischemic events, and accumulation of significant pericardial effusions were similar in all groups. The results of this study demonstrate that both ibuprofen and indomethacin provide safe and effective symptomatic treatment for postpericardiotomy syndrome. PMID- 2200932 TI - Segmental tricuspid annuloplasty: a new technique. PMID- 2200933 TI - Supravital staining of murine brain with methylene blue according to the Cajal method: a simple and reliable preparation technique for embedding in paraffin. AB - Saturated methylene blue solutions or powder were applied with a brush to fresh, unfixed brain slabs. The specimens were then exposed to ambient oxygen in a moist chamber. Fixation was done by application of an ammonium heptamolybdate solution followed by a phosphate-buffered paraformaldehyde/glutaraldehyde mixture with phosphomolybdic acid added. The specimens were dehydrated in tert-butanol before embedding in paraffin. Because of its high specificity for perikarya and for varicose, unmyelinated nerve fibres, this technique is a helpful supplement to other histological methods, particularly to myelin staining techniques. It is therefore well-suited for routine use in neuroanatomical research. PMID- 2200934 TI - Financial leases in the hospital industry. An analysis of California hospitals. AB - Using California hospital data, this study examined the extent to which capital leases displace debt in the hospital industry. Moreover, it analyzed how hospital and financial variables affect utilization of lease financing. In contrast to the theoretic belief that lease financing displaces debt financing, the results showed a greater use of debt with leases. The study also found smaller, free standing facilities with a greater investment in plant and equipment employed the lease option. PMID- 2200935 TI - [Combined treatment of gaseous gangrene with hyperbaric oxygen therapy, surgery and antibiotics. A national cooperative multicenter study]. AB - 85 confirmed gas gangrene cases from general hospitals where hyperbaric oxygen chambers with single or multiple places are available were reviewed. The diagnosis was made on the basic of muscle necrosis with the characteristic color and odor of the wound, and suggestive clinical and bacteriological findings. The treatment consisted on surgical excision, multiple antibiotic therapy, and hyperbaric oxygen at 3 absolute atmospheres. There was a male predominance (76.5%); 49.4% of them had previous risk factors; the origin of the disease was spontaneous in 18.8% of cases, after trauma in 37.6%, and after surgery in 43.5%. The surgery had been orthopedic in 18.8%, vascular in 16.5% and other in 1.2%. The lesion was in the lower limbs in 71.8%, with abdominal origin of propagation in 18.8% and perineal propagation in 8.2%. 44.7% of patients had shock on admission. The outcome was good in 50.6% of patients, who had a full recovery, and fair in 16.5%, who had minor sequelae or small re-amputations; this amounts to 67.1% of satisfactory evolutions. Outcome was poor in 20% in whom amputation or other major surgical procedures were required (p less than 0.05). Overall mortality rate was 20%, although only in 12.9% death directly related with gas gangrene. Mortality was significantly higher in women, in abdominal localization, and in patients with shock. It was 37.5% in spontaneous and 29.7% in postsurgical cases. There was no death in traumatic cases (p less than 0.005). Death directly related with the disease occurred in the first three days and nonrelated death after two weeks. More severe cases could be cared for in hospitals where multiple place hyperbaric oxygen chambers were available than in those with single place chambers, with a definite outcome towards cure or death with less intermediate situations. The relevant literature is reviewed. It is concluded that this combined therapeutic schedule has the best efficacy to treat gas gangrene, particularly in the more severe forms. PMID- 2200936 TI - [Rheumatoid arthritis and Sjogren's syndrome. Special reference to the course time of rheumatoid arthritis]. AB - The frequency of Sjogren's syndrome (SS) was evaluated in 45 patients with rheumatoid arthritis (RA). Subsequently, the clinical, biological and evolutive profiles of RA associated or not with SS were compared. The prevalence of definitive SS was 55%, while in 24% isolated data of gland involvement were found. The variables related with the development of SS in patients with RA were: sex, functional respiratory parameters, and, basically, the duration of RA. The latter relationship had a uniform association model, i.e., the prevalence of SS increased in a constant fashion following the duration increments of RA. The change of patients from negative to definite SS was uniform throughout the evolution of RA. PMID- 2200937 TI - [Attention: analysis and clinical implications]. PMID- 2200938 TI - Immunocytochemical studies on cholestatic factor in human liver with or without cholestasis. AB - The localization of the cholestatic factor (CF) was immunocytochemically investigated in liver biopsy specimens obtained from patients with various liver diseases. CF was detected in seven of nine patients with drug-induced liver injury, three of four with acute viral hepatitis, three of five with alcoholic liver injury and in the two patients with autoimmune hepatitis. Fourteen of these 15 CF-positive patients had jaundice in their clinical courses. CF was stained diffusely in the cytoplasm of hepatocytes throughout the lobules in a granular pattern. Electron-microscopically, it was localized on the ribosomes and polysomes as well as on the filamentous structures around the bile canaliculi. However, CF was not detected in liver specimens from normal controls and patients with primary biliary cirrhosis and extrahepatic biliary obstruction. These findings suggest that CF plays an important role in intrahepatic cholestasis in various liver diseases. PMID- 2200939 TI - [Malaria and retinal hemorrhages]. AB - A 24-year-old woman presented with retinal hemorrhages, back from a travel in Cameroon. She took a chloroquine chemoprophylaxis. We diagnosed a malaria due to Plasmodium falciparum with anemia, splenomegaly and low parasitemia. A speedy clinical and ophthalmological recovery was obtained with mefloquine therapy. We discuss physiopathology of such uncommon retinal damage during malaria. PMID- 2200940 TI - [Rheumatological aspects of infection with human immunodeficiency virus (HIV)]. AB - Since 1987, some works have been devoted to rheumatological manifestations appearing during the course of the HIV infection. If neurotropism of this retrovirus explains some misleading pseudo radicular aspects of the disease, sometimes revealing, inflammatory neuro-arthropathies are still under discussion. In Tropical Africa, increase of reactive arthritis of REITER's type seems to be correlated with the present epidemic outbreak. It is also admitted that HIV has a direct arthritic effect. These two facts lead to elaborate several pathogenic hypothesis concerning rheumatoid arthritis and spondylarthritis. On the other side, some systemic diseases may appear or be simulated at the occasion of the HIV infection, in particular, some lupoid manifestations. During AIDS, lymphocytic depletion may be at the origin of series of biological abnormalities that have to be known in order to mislead diagnosis. PMID- 2200941 TI - Structure-function analyses of Shiga toxin and the Shiga-like toxins. PMID- 2200942 TI - Nucleotide sequence analysis of a provirus derived from an individual with tropical spastic paraparesis. AB - Human T-cell lymphotropic virus type 1 (HTLV-1), the cause of inapparent infections and T-cell leukemias and lymphomas, has also been implicated in two chronic neurological diseases, tropical spastic paraparesis (TSP) and HTLV-1 associated myelopathy (HAM). We initiated a search for a neurotropic variant of HTLV-1 that might be responsible for these chronic progressive myelopathies by cloning and sequencing a provirus from a T-cell line from an individual with TSP. The LTRs and genes of the TSP provirus differ from HTLV-1 by 20-30 nucleotides in each region, but none of the substitutions ostensibly affect functional sites with the exception of the env gene. We document one substitution in the region encoding gp46 common to TSP and HAM proviruses and a mutation that introduces two stop codons in the region encoding gp21. The latter should delete about 100 amino acids from the transmembrane anchor, and, for this reason, the progeny of the sequenced provirus are likely to be defective viruses, maintained in the culture through coinfection of cells with wild-type non-defective HTLV-1. While defective viruses could be responsible for persistent infection of the nervous system in TSP, this cannot be generally the case as we show that HTLV-1 DNA amplified from cell lines from two other individuals with TSP lacked the stop codons. Similarly, comparisons of DNA amplified from HTLV-1 DNA in cases of ATL, HAM, and TSP did not establish a correlation between the mutation in gp46 and neurological disease. The issue of neurotropic variants in HTLV-1 associated neurological disease thus remains an open one which may be resolved in the future by examining proviruses in cells in the lesions in the nervous system; or proviruses in ATL and HAM/TSP which differ in their ability to replicate in glial or neuronal cells. PMID- 2200943 TI - In vivo and in vitro expression of outer membrane components of Haemophilus influenzae. AB - The outer membrane protein composition of Haemophilus influenzae grown under a variety of culture conditions including growth in sputum and serum, and intraperitoneally in rats was analyzed. The pattern of the major outer membrane proteins, a, b,c, d, e and P6 remained very similar under all these conditions. Outer membrane proteins expressed during iron limitation were also expressed in bacteria growing in rats, in serum or in sputum. To determine the expression of the major outer membrane proteins and lipopolysaccharide in patient materials (sputum, cerebrospinal fluid, postmortem tissue) monoclonal antibodies specific for the outer membrane proteins a, b,c, d and P6 as well as lipopolysaccharide were used in immunoblotting. They showed the same reaction patterns with bacteria in the patient materials as with the bacteria isolated from these specimens. We conclude that the major outer membrane components expressed under in vitro conditions are also expressed in various clinical materials during infection. PMID- 2200944 TI - Restriction site mutation analysis, a proposed methodology for the detection and study of DNA base changes following mutagen exposure. AB - We propose a methodology for the detection of DNA base changes in restriction enzyme recognition sites. The restriction site mutation (RSM) technique is based upon the detection of DNA sequences resistant to the cutting action of specific restriction enzymes and the amplification of these resistant sequences using the polymerase chain reaction. As outlined, the RSM method has the potential for use in the study of induced base changes in any species, tissue and genes of known DNA sequence for which unique DNA primers are available, and which contains a number of unique restriction enzyme recognition sites. PMID- 2200945 TI - Mutagenicity test for unstable compounds, such as 5,6-dihydroxyindole, using an Escherichia coli HB101/pBR322 transfection system. AB - A mutagenicity test for unstable chemical compounds has been devised. The test makes use of (i) in vitro treatment of plasmid pBR322 with the putative mutagen (ii) subsequent transfection of Escherichia coli HB101; (iii) selection either on tetracycline- or ampicillin-containing Eugon agar (iv) cross-antibiotic replica plating and recovery of single antibiotic resistant colonies (v) restriction analysis of pBR322 isolated from single antibiotic resistant colonies. In this work the test has been used to assess the mutagenicity of 5,6-dihydroxyindole, a cytotoxic intermediate of melanin biosynthesis. PMID- 2200946 TI - Studies on the induction of gene mutations in bacterial and mammalian cells by the ring-opened benzene metabolites trans,trans-muconaldehyde and trans,trans muconic acid. AB - t,t-Muconaldehyde and t,t-muconic acid have been investigated for the induction of gene mutations in Salmonella typhimurium (reversion of the his- strains TA97, TA98, TA100, TA102, TA104 and TA1535), Escherichia coli (reversion of the trp- strain WP2 uvrA) and Chinese hamster V79 cells (acquisition of resistance toward 6-thioguanine). t,t-Muconaldehyde proved weakly mutagenic in strain TA104 in the presence and absence of NADPH-fortified postmitochondrial fraction from rat liver homogenate (S9 mix). In strains TA97, TA100 and TA102, weak positive responses were observed only in the presence of S9 mix. In strains TA98, TA1535 and WP2 uvrA, the result was negative. In V79 cells, the mutation frequency was increased from approximately 7 X 10(-6) to 90 X 10(-6) in cultures exposed to t,t muconaldehyde at optimal concentration (1.7-3 microM in separate experiments). The concentration-response curve showed pronounced hyperlinearity, with no mutagenic effect being observed at a third of the optimal concentration. t,t Muconic acid was greater than 100 times less toxic than t,t-muconaldehyde in both bacteria and mammalian cells, and it did not show any mutagenic effect. These results complete a previous mutagenicity study, carried out on benzene and 13 metabolites. It is concluded that the newly investigated metabolites cannot account for the bacterial mutagenicity of bioactivated benzene and benzene-trans 1,2-dihydrodiol, since these compounds exhibited their strongest response in strain TA1535. t,t-Muconaldehyde showed similarities in its mutagenicity to p benzoquinone and hydroquinone. All three compounds showed, at most, weak effects in bacteria, but were strongly mutagenic in V79 cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2200947 TI - The comparative responses of Salmonella typhimurium TA1537 and TA97a to a range of reference mutagens and novel compounds. AB - Salmonella typhimurium TA97a was added to the set of indicator strains routinely used for the Ames test in this laboratory (TA1535, TA1537, TA1538, TA98 and TA100) for a trial period during which a total of approximately 40 reference mutagens and novel pharmaceutical compounds were examined. The conclusions from this trial were as follows: (i) there are agents mutagenic for TA1537 which are not detected by TA97a. (ii) except for agents requiring the R factor plasmid, TA97a shows no increased sensitivity to mutagens when compared with TA1537 and (iii) nearly all the limited published database is for the original isolate, TA97, rather than TA97a, and the results obtained here indicate significant differences in response between the two; TA97a remains, therefore, essentially unvalidated. PMID- 2200948 TI - Comparison of Salmonella typhimurium TA102 with Escherichia coli WP2 tester strains. AB - In 1982, Levin et al. published a paper describing a new Salmonella typhimurium strain, TA102, for detecting mutagenic agents that react preferentially with AT base pairs. This strain has an AT base pair at the critical mutation site within the hisG gene, which is located on a multicopy plasmid, pAQ1; the chromosomal copy of the hisG gene has been deleted. It also has an intact excision repair system, thus facilitating the detection of cross-linking agents, and carries the mutator plasmid, pKM101. Although TA102 has been shown to be reverted by certain mutagenic agents that are not detected in the usual battery of strains (TA1535, TA1537, TA1538, TA98 and TA100), there has been a general reluctance within the field to include TA102 as one of the standard screening strains. This may in part result from the difficulties which have been experienced in many laboratories in maintaining the strain, and in obtaining reproducible spontaneous and induced revertant counts. At Glaxo we routinely include certain Escherichia coli strains in our microbial test battery, and were aware that some of the genetic features offered by TA102 were already being covered by these strains. For example, E.coli WP2 (pKM101) has an AT base pair at the critical mutation site within the trpE gene, is excision proficient (and thus will detect cross-linking agents) and carries the pKM101 plasmid to enhance error-prone repair. From the published literature it was apparent that a number of the 'TA102 specific' mutagens could be detected in E.coli e.g. neocarzinostatin, UV and 8-MOP plus UV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2200949 TI - Vanadium: genetical and biochemical investigations. AB - Ammonium metavanadate was studied for its ability to induce mitotic gene conversion and reverse point mutation in the D7 strain of Saccharomyces cerevisiae. Metavanadate increased the convertant and revertant frequencies; the highest activity was observed without metabolic activation. This indicated that the S9 hepatic fraction and yeast cells in logarithmic phase (and containing a high level of cytochrome P450) biotransform vanadate, probably reducing it to vanadyl. In addition, the effect of ammonium metavanadate on the hepatic monooxygenase system was studied in mice by measuring the level of cytochrome P450 and determining the activities of aminopyrine N-demethylase, p-nitroanisole O-demethylase and 7-ethoxycoumarin O-deethylase in mouse liver microsomal fraction. The results indicated that this compound reduced mono-oxygenase activity and also the level of cytochrome P450. PMID- 2200950 TI - Nonlinear magnetic stereotaxis: three-dimensional, in vivo remote magnetic manipulation of a small object in canine brain. AB - In a series of in vivo experiments on five adult canines, a small cylindrical permanent magnet (approximately 5-mm diameter x 5 mm long) was magnetically moved under fluoroscopic guidance from an occipital-lobe burr hole to a predetermined destination within the brain and then removed. On three of the animals, dorsal and temporal skull markers were used to establish a coordinate system against which the motions of the seed were referenced. These procedures were sufficiently accurate to permit the guided motion of the seed along nonlinear paths within the brain, including traversal of the midline through the corpus callosum. For removal, the seed could be steered either to a frontal lobe location for extraction through an auxiliary burr hole, or back to the same burr hole through which it had been inserted. This article discusses the way in which stereotactic motions were obtained, the performance limits of the instrumentation and the precision of motion achieved. PMID- 2200951 TI - [Practical medicine. Balloon valvuloplasty in heart valve stenosis]. PMID- 2200952 TI - [The fate of hemoglobin in the gastrointestinal tract and its significance for the diagnosis of hemorrhages]. PMID- 2200953 TI - Biochemical characterization of the cholecystokinin receptor on CHP212 human neuroblastoma cells. AB - Cholecystokinin (CCK) receptors reside on a large number of cell types along the digestive tract and in the nervous system. A human neuroblastoma cell line (CHP212) has recently been described to express a type A receptor, with structural specificity similar to that on pancreatic acinar cells and gall bladder smooth muscle cells but different from the predominant type of binding site found in brain (type B). In this work, we have performed photoaffinity labeling and protease peptide mapping of the CHP212 receptor and have compared it to other type A CCK receptors. 125I-D-Tyr-Gly-[(Nle28,31,pNO2-Phe33)-CCK-26-33], a probe that possesses a photolabile residue at position 33 within the theoretical receptor-binding domain of this hormone, specifically labeled a Mr = 80,000-90,000 glycoprotein on this cell line, while labeling larger proteins (Mr = 85,000-95,000) on rat pancreas and human gall bladder. Deglycosylation with endo-beta-N-acetylglucosaminidase F yielded bands of Mr = 43,000 from CHP212 and gall bladder and Mr = 42,000 from pancreas. Peptide mapping of the deglycosylated bands using Staphylococcus aureus V8 protease demonstrated identical patterns in CHP212 and gall bladder and a similar but different pattern in pancreas. Thus, although possessing heterogeneity in their carbohydrate domains, CCK receptors on human neuroblastoma cells (CHP212) and human gall bladder smooth muscle cells have highly similar or identical protein cores. The core protein on another type A CCK receptor, from rat pancreas, appears to differ from these, likely representing molecular heterogeneity between species. PMID- 2200955 TI - High levels of chromosome instability in polyploids of Saccharomyces cerevisiae. AB - The yeast Saccharomyces cerevisiae was used to study the genetic consequences of polyploidy in a unicellular organism. Isogenic diploid (2N), triploid (3N) and tetraploid (4N) strains with a genetically marked chromosome VII (cyh2-leu1-CEN7 ade6) were constructed and were used to follow the loss of one, two or three chromosome VII's during mitosis. We found that as ploidy increased, the frequency of loss of a single chromosome VII increased: Loss of one copy of chromosome VII occurred at a rate nearly 30-fold higher in triploids and approximately 1000-fold higher in tetraploids than in the diploid. Loss of two or three copies occurred at an even greater frequency. These findings suggest either that aneuploidy (3N 1, 3N-2, 4N-1, 4N-2, 4N-3) increases genome instability or that multiple chromosome loss events occur at high frequency. Polyploidy appears to dramatically increase chromosome loss, presumably due to the inability of the cell to undergo proper chromosome segregation. The biological significance and possible causes for the instability of polyploidy in unicellular organisms such as yeast are discussed. PMID- 2200954 TI - Internalization of endothelin by cultured human vascular smooth muscle cells: characterization and physiological significance. AB - The binding and internalization of 125I-endothelin (125I-ET-1) was studied in cultured human vascular smooth muscle cells (hVSMC). Discrimination between surface-bound and internalized radiolabeled ligand was achieved using either acetic acid or trypsin treatment of cell layers, with the two procedures yielding comparable results. Total cellular 125I-ET-1 binding hVSMC at 37 degrees was rapid and reached near equilibrium within 30 min. Such binding could be resolved into surface-bound (acid/trypsin-sensitive) and internalized (acid/trypsin resistant) components. The accumulation of internalized 125I-ET-1 was temperature dependent and occurred at 37 degrees (t1/2 approximately 15 min) but not at 4 degrees. Internalization of 125I-ET-1 by hVSMC was reversibly inhibited by the transglutaminase inhibitor dansylcadaverine (half-maximal inhibitory concentration, approximately 400 microM). Cytosolic acidification of hVSMC (from pH approximately 6.8 to approximately 6.3) by incubation with potassium acetate in a choline buffer also inhibited 125I-ET-1 internalization. Our observation indicate that smooth muscle cells internalize ET-1 via the clathrin-mediated endocytotic pathway. Dansylcadaverine and other inhibitors of transglutaminase inhibited ET-1-stimulated inositol phospholipid hydrolysis in hVSMC and decreased ET-1-induced vasoconstriction in isolated endothelium-denuded blood vessels. Internalization of ET-1 may, therefore, be relevant to the characteristically protracted physiological effects of this peptide on the vasculature. PMID- 2200956 TI - Epoxides: comparison of the induction of SOS repair in Escherichia coli PQ37 and the bacterial mutagenicity in the Ames test. AB - The genotoxicity of 51 epoxides is studied with the SOS-Chromotest using Escherichia coli PQ37 as tester strain. The results obtained with this test system are compared with results of the Ames test. Out of 51 epoxides, 39 are shown to be mutagenic in Salmonella typhimurium whereas only 27 mutagenic epoxides induced the SOS response in Escherichia coli PQ37. PMID- 2200957 TI - Consideration of both genotoxic and nongenotoxic mechanisms in predicting carcinogenic potential. AB - Bacterial and cell culture genotoxicity assays have proven to be valuable in the identification of DNA reactive carcinogens because mutational events that alter the activity or expression of growth control genes are a key step in carcinogenesis. The addition of metabolizing enzymes to these assays have expanded the ability to identify agents that require metabolic activation. However, chemical carcinogenesis is a complex process dependent on toxicokinetics and involving at least steps of initiation, promotion and progression. Identification of those carcinogens that are activated in a manner unique to the whole animal, such as 2,6-dinitrotoluene, require in vivo genotoxicity assays. There are many different classes of non-DNA reactive carcinogens ranging from the potent promoter 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) that acts through a specific receptor, to compounds that alter growth control, such as phenobarbital. Many compounds, such as saccharin, appear to exhibit initiating, promotional and/or carcinogenic activity as events secondary to induced cytotoxicity and cell proliferation seen only at the chronic lifetime maximum tolerated doses mandated in rodent bioassays. Simple plus/minus vs. carcinogen/noncarcinogen comparisons used to validate the predictivity of bacterial and cell culture genotoxicity assays have revealed that a more comprehensive analysis will be required to account for the carcinogenicity of so many diverse chemical agents. Predictive assays and risk assessments for the numerous types of nongenotoxic carcinogens will require understanding of their mechanism of action, reasons for target organ and species specificity, and the quantitative dose-response relationships between endpoints such as induced cell proliferation and carcinogenic potential. PMID- 2200958 TI - Review of the genotoxicity and carcinogenicity of 4,4'-methylene-dianiline and 4,4'-methylene-bis-2-chloroaniline. AB - 4,4'-Methylene-dianiline (MDA) and 4,4'-methylene-bis-2-chloroaniline (MOCA) are polycyclic aromatic amines that are currently used in industry. Both compounds have been found to be bacterial mutagens and to be positive in a number of assays for genotoxicity. In animal studies, MDA has induced thyroid and liver neoplasms while exposure to MOCA resulted in a variety of tumors including those of the liver, mammary gland and bladder. Epidemiologic proof of human carcinogenicity of both compounds is lacking; however, there is evidence that MOCA can be metabolized to mutagenic products by human tissue. In this paper, the major finding concerning the biotransformation, genotoxicity and carcinogenicity of MDA and MOCA are reviewed. PMID- 2200959 TI - Mutagenicity of commercial hair dyes and detection of 2,7-diaminophenazine. AB - Four commercial oxidative-type hair dye formulations, A, B, C, and D, were treated with hydrogen peroxide (H2O2) to simulate normal conditions of use, and the oxidized hair dyes were tested for their mutagenicity in Salmonella typhimurium TA98 in the presence of a mammalian metabolic activation system (S9 mix). Most of them did not show obvious mutagenicity in the range of 1-25 microliters/plate and all exhibited bactericidal activity at 10 microliters/plate. In order to evaluate the mutagenicity of hair dyes both before and after H2O2 oxidation, rayon linked to a copper-phthalocyanine derivative (blue rayon) was used as an adsorbent for the elimination of interfering bactericidal compounds. Adsorbed compounds on blue rayon were eluted with ammoniacal methanol and eluents were subjected to the Ames test. The mutagenicity of the blue-rayon extracts in TA98 with S9 mix was increased by H2O2 oxidation. The blue-rayon extracts obtained from oxidized A and B were potent mutagens and reverted 334 and 999 colonies/10 microliters of original substance, respectively. In addition, 88 and 249 ng of 2,7-diaminophenazine, which was extremely mutagenic in TA98 with S9 mix, were detected in the extracts of 40 ml of the hair dye formulations A and B, respectively. The mutagenicity in oxidized hair dye formulations was successfully detected by use of blue-rayon extraction. 2,7 Diaminophenazine was only formed in the hair dye formulations containing m phenylenediamine by H2O2 oxidation. Therefore, attention needs to be paid to the use of m-phenylenediamine as a hair dye component, not only for its own toxicity but also for that of its oxidation products. PMID- 2200960 TI - A comparative study of mutagenic and SOS-inducing activity of biphenyls, phenanthrenequinones and fluorenones. AB - A total of 23 chemicals--biphenyls, phenanthrenequinones and fluorenones--were tested for mutagenicity towards Salmonella typhimurium strains TA1538, TA1535 and TA98. SOS-inducing activity of the same chemicals was studied in terms of the SOS inducing potency in Escherichia coli PQ37, using an automated instrument controlled by a dedicated computer program for the SOS Chromotest. Of the 23 chemicals studied 14 induced His+ revertants in S. typhimurium TA1538 hisD305 (-1 frameshift); none induced His+ reversions in TA1535 (base-pair substitution). The mutagenicity of the chemicals in S. typhimurium TA98 (pKM 101) was lower than in TA1538. There was a close correlation between mutagenicity and SOS-inducing activity of fluorenones and phenanthrenequinones. None of the biphenyls tested induced SOS response and this property does not depend upon the mutagenic activity of the chemicals. SOS Chromotest is particularly valid in detecting chemicals which give rise to base-pair substitutions through SOS induction. If positive results are obtained, the Salmonella assay may be omitted. However, this test cannot replace the Ames test especially for the primary screening of mutagenicity of chemicals with unknown structure. PMID- 2200961 TI - Characterisation and sequence of a protective rhoptry antigen from Plasmodium falciparum. AB - We have recently demonstrated that a non-polymorphic rhoptry antigen, RAP-1 (rhoptry associated protein-1), which is recognised by human immune serum, can successfully protect Saimiri monkeys from a lethal infection of Plasmodium falciparum malaria. In this report we further characterise the antigen, which consists of four major proteins of 80, 65, 42 and 40 kDa and two minor proteins of 77 and 70 kDa, and present the antigen's gene sequence. Monoclonal antibody evidence, autocatalytic processing and immunological cross-reactivity suggest that all components of this antigen are derived from the same precursor protein. The antigen is lipophilic, and disulphide bonding plays an important role in its structure. We discuss the structure and function of RAP-1 in the light of its deduced amino acid sequence and consider the relationship of this antigen to other rhoptry antigens of similar subunit size and composition. PMID- 2200962 TI - Characterization of a Trypanosoma cruzi specific nuclear repeated sequence. AB - We report the isolation of three different clones from a Trypanosoma cruzi genomic library bearing a common repeated sequence. This sequence is not tandemly repeated, and is dispersed on many chromosomes. All of the T. cruzi strains tested share this element. On the other hand, it is absent from the genome of other Kinetoplastida. The size of this element is about 10-12 kb, and its copy number is 220 in the T. cruzi Dm 28c genome. A transcript homologous to this sequence is detected in epimastigote forms of the parasite. PMID- 2200963 TI - Identification and characterization of a target antigen of a monoclonal antibody directed against Eimeria tenella merozoites. AB - Monoclonal antibodies (Mab) were produced against Eimeria tenella merozoites. A single Mab, LPMC-61, was selected because of its ability to bind to merozoites by indirect immunofluorescence assay (IFA) and to inhibit in vitro sporozoite development. Mab LPMC-61 reacts with an approx. 10-12-kDa merozoite polypeptide in reduced SDS-PAGE, but with an approx. 80-kDa protein in non-reduced SDS-PAGE. The monoclonal recognizes similarly sized polypeptides in E. tenella sporozoites, oocysts and schizonts. A partial cDNA (LPMC-61f) encoding the LPMC-61 antigen was identified from an E. tenella sporozoite cDNA library in bacteriophage lambda gt11. In addition to Mab LPMC-61, the recombinant beta-galactosidase/LPMC-61f fusion protein is recognized by hyperimmune rabbit anti-E. tenella sporozoite serum, rabbit anti-E. tenella merozoite serum, and E. tenella-infected and immune chicken sera. DNA sequencing of LPMC-61f cDNA showed that the putative protein has an unusual tandem, non-perfect repeated sequence, with glutamine comprising about 48% of the predicted amino acids. A hydropathicity plot of the predicted amino acid sequence shows a central hydrophilic region, consisting of the repeated sequences, surrounded by hydrophobic regions on both sides. Since the merozoite stage of avian Eimeria has been implicated in the induction of a protective immune response in chickens, LPMC-61 may be an important immunogen for use as a vaccine against E. tenella. PMID- 2200964 TI - Expression and characterization of glucose-6-phosphate dehydrogenase of Plasmodium falciparum. AB - Glucose-6-phosphate dehydrogenase (G6PD) from Plasmodium falciparum has been detected previously in cultures of parasites grown in G6PD-deficient red blood cells. Using polyacrylamide gel electrophoresis, a semi-quantitative assay has been developed to compare the level of the parasite enzyme activity in G6PD normal and in G6PD-deficient host cells. The results do not support the previous contention that the host cell G6PD-deficiency necessarily affects the level of expression of the parasite enzyme. The plasmodial enzyme was partially purified from extracts of parasites prepared by digitonin lysis of infected red blood cells, and its distinctive biochemical properties are described. P. falciparum G6PD has a KmG6P of 27 microM, a KmNADP of 4.5 microM, and KiNADPH of 4.5 microM, indicating an affinity for all its main ligands much higher than that of normal human red cell G6PD. PMID- 2200965 TI - Comparison of magnetic resonance imaging and ultrasonography in staging early prostate cancer. Results of a multi-institutional cooperative trial. AB - BACKGROUND: In 1987, a cooperative study group consisting of five institutions was formed to determine the relative benefits of magnetic resonance imaging (MRI) and endorectal (transrectal) ultrasonography in evaluating patients with clinically localized prostate cancer (stage Ta or Tb). METHODS: Over a period of 15 months, 230 patients were entered into the study and evaluated with identical imaging techniques. We compared imaging results with information obtained at the time of surgery and on pathological analysis. RESULTS: MRI correctly staged 77 percent of cases of advanced disease and 57 percent of cases of localized disease; the corresponding figures for ultrasonography were 66 and 46 percent (P not significant). These figures did not vary significantly between readers; moreover, simultaneous interpretation of MRI and ultrasound scans did not improve accuracy. In terms of detecting and localizing lesions, MRI identified only 60 percent of all malignant tumors measuring more than 5 mm on pathological analysis and ultrasonography identified only 59 percent. CONCLUSIONS: The MRI and ultrasonography equipment that is currently available is not highly accurate in staging early prostate cancer, mainly because neither technique has the ability to identify microscopic spread of disease. Further evaluation with improved equipment may improve the accuracy of these techniques. PMID- 2200966 TI - A controlled trial of corticosteroids in children with corrosive injury of the esophagus. AB - BACKGROUND: It is controversial whether treatment with corticosteroids reduces stricture formation in the esophagus after the ingestion of caustic material. METHODS: We conducted a prospective study over an 18-year period in which 60 children (median age, 2 years) with esophageal injury from the ingestion of caustic material were assigned randomly to treatment either with or without corticosteroids. The corticosteroids were given initially as prednisolon (2 mg per kilogram of body weight per day intravenously) and then as prednisone orally to complete a three-week course. All patients were evaluated by esophagoscopy within 24 hours of the ingestion. Those with moderate or severe esophageal injury had repeat esophagoscopy and barium swallow at follow-up. RESULTS: Esophageal strictures developed in 10 of the 31 children treated with corticosteroids and in 11 of the 29 controls (P not significant). Four children in the steroid group and seven in the control group eventually required esophageal replacement (P not significant). All but 1 of the 21 children with strictures had severe circumferential burns on initial esophagoscopy. CONCLUSIONS: There appears to be no benefit from the use of steroids to treat children who have ingested a caustic substance. The development of esophageal stricture was related only to the severity of the corrosive injury. PMID- 2200967 TI - Severe streptococcal axillary lymphadenitis. PMID- 2200968 TI - Abrupt changes in flagellar rotation observed by laser dark-field microscopy. AB - Bacteria such as Escherichia coli and Salmonella typhimurium swim by rotating their flagella, each of which consists of an external helical filament and a rotary motor embedded in the cell surface. The function of the flagellar motor has been examined mainly by tethering the flagellar filament to a glass slide and observing the resultant rotation of the cell body. But under these conditions the motor operates at a very low speed (about 10 r.p.s.) owing to the unnaturally high load conditions inherent in this technique. Lowe et al. analysed the frequency of light scattered from swimming cells to estimate the average rotation speed of flagellar bundles of E. coli as about 270 r.p.s. To analyse motor function in more detail, however, measurement of high-speed rotation of a single flagellum (at low load) with a temporal resolution better than 1 ms is needed. We have now developed a new method--laser dark-field microscopy--which fulfils these requirements. We find that although the average rotation speed of S. typhimurium flagella is rather stable, there are occasional abrupt slowdowns, pauses and reversals (accomplished within 1 ms). These changes were frequently observed in mutants defective in one of the motor components (called the switch complex), suggesting that this component is important not only in switching rotational direction but also in torque generation or regulation. PMID- 2200969 TI - [Tracheotomy and intubation]. PMID- 2200971 TI - [Tropical malaria; does prophylaxis become simpler?]. PMID- 2200970 TI - [Blood viscosity in pregnancy complications]. PMID- 2200972 TI - [Tracheotomy and intubation]. PMID- 2200973 TI - [Occipital transtentorial approach for pineal tumors by lateral-semiprone position]. PMID- 2200974 TI - Decreased striatal release of acetylcholine following withdrawal from long-term treatment with haloperidol: modulation by cholinergic, dopamine-D1 and -D2 mechanisms. AB - The effect of chronic treatment with haloperidol (2.7-5.3 mumol/kg/day) on K(+) evoked release of [3H]acetylcholine (ACh) from superfused slices of the striatum was assessed. Acute injections of haloperidol (0.7-13.3 mumol/kg) produced 5-54% increases in the release of [3H]ACh in the striatum. Chronic treatment with haloperidol for 2.5 and 5 months also resulted in enhanced release of [3H]ACh in the striatum (28-35%). However, withdrawal from 2.5 and 5 months of treatment produced 34 and 38% decreases in K(+)-evoked release of [3H]ACh in the striatum, respectively. The drug SKF 38393 (D1-agonist), produced concentration-dependent (0.1-10 microM) increases (24-59%) in the release of [3H]ACh in the striatum which were blocked by the selective D1-antagonist, SCH 23390. The effect of stimulation of D1-receptors was significantly reduced after 2.5 or 5 months of chronic treatment with haloperidol. Both LY171555 (D2-agonist) and carbachol (muscarinic agonist) produced concentration-dependent (0.1-10 microM) inhibitions of the release of [3H]ACh in the striatum (LY171555: 28-62%; carbachol: 23-63%). Long-term treatment with haloperidol (2.5 and 5 months) elicited increases in sensitivity to the effect of LY171555, while the effect of carbachol was diminished only after the 5-month treatment period. These findings demonstrate that withdrawal from chronic exposure to haloperidol in the rat results in a reduction in the release of acetylcholine in the striatum. This effect is accompanied by (1) attenuated dopaminergic D1 mechanisms which ordinarily facilitate evoked release of ACh, (2) enhanced D2 mechanism which elicits inhibition of the release of ACh in the striatum, and (3) diminished muscarinic inhibitory influence which regulates the release of ACh. PMID- 2200975 TI - Excitotoxic lesions of the paraventricular hypothalamus: metabolic and cardiac effects. AB - The excitotoxin, N-methyl-D-aspartic acid (NMDA), was used to lesion cell bodies, but not fibers-of-passage, in the paraventricular hypothalamus. Bilateral injections of NMDA (12.6 nmol/100 nl) were made into the paraventricular hypothalamus in halothane-anesthetized male Sprague-Dawley rats. Water intake, food intake, urine output and body weight were measured daily for 26 days after lesioning. Lesioned rats exhibited a modest, but significant, reduction in the rate of gain of body weight, which was most closely correlated with decreases in food intake. Water intake and urine output were not significantly different among the groups. Resting blood pressure, heart rate and baroreflex sensitivity (using the infusion of phenylephrine method) were similar in conscious animals of both groups, 4-5 weeks after lesioning. Neuronal loss, primarily of parvocellular elements, was evident in the paraventricular hypothalamus and neuronal loss frequently extended into the ventro-medial thalamus adjacent to the paraventricular hypothalamus in NMDA-lesioned rats. In a second experiment, injections of NMDA were given acutely into the paraventricular hypothalamus of halothane-anesthetized rats. Upon recovery from anesthesia, behavioral excitation and increases in blood pressure and heart rate were evident for 1-2 hr. Histological examination of hearts taken 48 hr after injection of NMDA revealed a largely mononuclear inflammatory infiltration, hyperemia and myocardial hemorrhage and focal myocardial necrosis. Inflammatory and degenerative changes were most prominent in the left ventricular subendocardium. The cardiomyopathy possessed similarities with catecholamine-induced myocardial necrosis. The results indicated that NMDA-induced lesions of parvocellular elements of the paraventricular hypothalamus did not cause hyperphagia or obesity or alter the resting systemic circulatory function. However, an inflammatory cardiomyopathy, termed "excitotoxin-induced myocardial necrosis", was associated with injections of NMDA into the hypothalamus. Excitotoxin-induced myocardial necrosis may complicate any hemodynamic studies performed in rats in which lesions of the CNS have been produced by means of application of excitotoxins. PMID- 2200976 TI - Radiofrequency cingulotomy for intractable cancer pain using stereotaxis guided by magnetic resonance imaging. AB - This study presents a new and simplified method of creating cingulate gyrus lesions by using stereotaxis guided by magnetic resonance imaging (MRI). Previous methods have utilized ventriculogram-guided stereotaxis requiring indirect cingulate gyrus localization and general anesthesia. With the present technique a BRW stereotactic frame was applied with the patient under local anesthesia. An MRI scan was performed using a T1 signal (TR, 600 ms; TE, 30 ms) in the coronal plane with 5-mm thick sections spaced every 6 mm. The coronal slice 24 mm posterior to the anterior tip of lateral ventricle was identified. The center of each (right and left) cingulate gyrus was identified as a target area, and appropriate coordinates were determined. Approach parameters were calculated for the right and left gyri using an azimuth of 45 degrees and 315 degrees, respectively, and a declination of 45 degrees. A radiofrequency electrode was stereotactically placed so that the electrode tip was at a target point which was the center of the cingulate gyrus. A radiofrequency lesion (75 degrees, 60 seconds) was made in each hemisphere's cingulate gyrus. Four patients with intractable terminal cancer pain have been initially treated in this manner. The lesions were well-localized on postoperative MRI scans. There have been no complications except for perilesional edema for 10 days in 1 patient (treated with longer radiofrequency settings that have subsequently been modified).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2200977 TI - Atypical subependymoma of the spinal cord: ultrastructural and immunohistochemical studies. AB - A 76-year-old woman with a 2-year history of progressive weakness of the left arm and leg underwent a laminectomy for an intradural, extramedullary, pedunculated subependymoma involving the meninges and spinal nerve roots at C7-T1. Eight months later, another operation was necessary for an intramedullary neoplasm at C3-T4. This latter tumor consisted of small, poorly developed cells, large atypical astrocytes, and ependymal cells. Neither ependymal rosettes nor papillary formations were present. Ultrastructural studies showed some features of ependymal differentiation of the large "astrocytic" cells. This case illustrates an unusual pattern of extramedullary and intramedullary presentations of subependymoma and a spectrum of cellular differentiation of neoplastic subependymal glia. PMID- 2200978 TI - Stereotactic guiding tube for open-system endoscopy: a new approach for the stereotactic endoscopic resection of intra-axial brain tumors. AB - Stereotactic endoscopic resection of intra-axial brain tumors using a newly developed endoscopic system consisting of a stereotactic guiding tube and a fine endoscope is reported. The stereotactically inserted guiding tube acts in the place of brain retractors to expose deep-seated pathological lesions, which are then visualized by means of a fine endoscope. The lesions may then be treated by various microsurgical techniques such as laser vaporization. Fifteen intra-axial lesions were operated on by this method using a guiding tube of 8 mm in outer diameter without significant complications. Seven small lesions measuring 3 to 26 mm in maximal diameter were resected totally. Eight large lesions, including two highly vascularized tumors, were examined by biopsy and resected partially through a burr hole with complete hemostasis under direct vision. This system is particularly useful for removing small intra-axial tumors in deep or eloquent areas difficult to resect using ordinary surgical techniques. It will also be applicable for other stereotactic operations that require accuracy and minimum invasiveness with complete hemostasis under direct visualization. PMID- 2200980 TI - Clinical manifestations of Lyme disease. PMID- 2200981 TI - Lyme disease during pregnancy. PMID- 2200979 TI - NMDA and quisqualate reduce a Ca-dependent K+ current by a protein kinase mediated mechanism. AB - Stimulation of N-methyl-D-aspartate (NMDA) or quisqualate (Quis) receptors by submicromolar concentrations of NMDA or Quis but not alpha-amino-3-hydroxy-5 methyl-4-isoxazolepropionic acid (AMPA) reduced post-spike train after hyperpolarizations (AHPs) and blocked the underlying Iahp in dentate granule (DG) neurones in vitro. The NMDA but not Quis action was blocked by the NMDA receptor blocker 2-D,L-aminophosphonovaleric acid (APV). Actions of both NMDA and Quis were abolished by isoquinolinesulphonyl-2-methyl-piperazine dihydrochloride (H 7), an inhibitor of several protein kinases. These data suggest that there is a link between excitatory amino acid receptor activation, the protein kinase system, and neuronal excitability. PMID- 2200982 TI - Neurological manifestations of Lyme disease. PMID- 2200983 TI - Immunology of Lyme disease. AB - B. burgdorferi is an organism capable of modifying the immune response of its human hosts in a number of specific and nonspecific ways. An understanding of immune changes can help with diagnostic and therapeutic decisions in Lyme disease. PMID- 2200984 TI - Lyme disease in small animals. PMID- 2200985 TI - Lyme disease in large animals. PMID- 2200987 TI - Avicenna, problem solving, and creativity during sleep. PMID- 2200986 TI - Aeromedical emergency trauma services and mortality reduction in rural areas. PMID- 2200988 TI - Anticoagulants and stroke prevention: the current evidence. PMID- 2200989 TI - Fenoterol: the evidence leading to restriction of it use. PMID- 2200990 TI - The psychoneuroimmune network. PMID- 2200991 TI - Models of renal blood flow and their use in the detection of renal artery stenosis. AB - First-pass studies of renal blood flow using 99Tcm-DTPA have been analysed in normotensive patients and those with renal artery stenosis. One and two component models of renal blood flow were examined for their ability to discriminate between these two groups. Using a two component model, 5/7 kidneys with proven renal artery stenosis were identified, with 38/40 kidneys in normotensive patients lying within the defined normal range. The two kidneys not detected by this technique both had extremely poor function. This model was also applied to other hypertensive patients referred for routine screening and appears promising in increasing the specificity of the 99Tcm-DTPA study for detecting renal artery stenosis. PMID- 2200992 TI - Type VI collagen in healing rabbit corneal wounds. AB - A type-specific monoclonal antibody was used to examine the localization of type VI collagen in healing full-thickness corneal wounds (3 mm in diameter) in rabbits. By immunofluorescence, in 1-week-old wounds, type VI collagen was found only at the wound periphery. Subsequently, type VI collagen showed a rapid increase throughout the wounded area. In 3-week-old wounds, type VI collagen immunofluorescence had a laminar pattern as seen in normal corneal stroma, although it was irregular in arrangement. By electron-microscopic immunohistochemistry, type VI collagen was found in the pericellular region of fibroblastic cells possibly derived from keratocytes. These results suggest that type VI collagen might originate from the fibroblastic cells and play an important role in the regeneration of the corneal lamellar structure. PMID- 2200993 TI - Suppression of macrophage-mediated antibody-dependent killing of Schistosoma mansoni larvae by concanavalin A stimulated spleen cell-derived factor(s). AB - Culture supernatants (sup) from rat spleen cells stimulated with concanavalin A (Con A) sepharose 4B suppressed schistosomulum killing by macrophages in a system of antibody-dependent cell-mediated cytotoxicity (ADCC). (a) The suppressive effect of the sup was strongest when they were added to cultures at the start of the ADCC assay, and it was decreased when sup were added to cultures in which the ADCC assay had begun more than 3 h previously. (b) From the results of various experiments in ADCC reaction, it was suggested that the suppressive factor(s) inhibited at least in part the interaction between macrophages and antibodies which had been bound to schistosomula, and that the suppressive factor(s) was bound to the macrophage side. (c) The suppressive activity was partially inactivated by treatment at 56 degrees C for 30 min, and it was lost almost completely by the treatment at 100 degrees C for 10 min. (d) The suppressive factor(s) differed from known cytokines such as interleukin 1 (IL-1), interleukin 2 (IL-2), granulocyte-macrophage-colony stimulating factor (GM-CSF), interferon gamma (IFN-gamma), and tumour necrosis factor (TNF). PMID- 2200994 TI - [Randomized study of cefatrizine versus cefaclor in conjunctivitis otitis syndrome]. AB - The association conjunctivitis-otitis is highly suggestive of Haemophilus influenzae infection. This conjunctivitis otitis syndrome could be a good model to assess the efficacy of different antibiotic regimen in the treatment of acute otitis media due to HI without tympanocentesis. This prospective randomized trial compared the efficacy of two orally cephalosporins which demonstrate in vitro an activity against HI. This study was conducted from 4.20.1988 to 3.15.1989 and involved 73 children with COS examined in an outpatient clinic. The mean age was 17.7 months. Before treatment culture were taken from the lower palpebral conjunctivae. 81 strains was found: HI 61 (beta-lactamase-producing 15), Streptococcus pneumoniae 16, Branhamella Catarrhalis 4. The 73 patients were treated with 40 to 50 mg/kg/day of the test drug for ten days, 25 with Cefaclor in 3 divided dose (group 1), 24 with Cefatrizine in 3 divided dose (group 2), 24 with Cefatrizine in 2 divided dose (group 3). The recoveries was obtained in 17/25 in the group 1, 18/24 in the group 2, 15/24 in the group 3. There was no significant difference between the 3 groups. PMID- 2200996 TI - [Efficacy of the combination of ceftazidime/vancomycin in the first line treatment of infection in neutropenic children]. AB - Infection is the first reason of mortality in children with bone marrow aplasia. It justifies the immediate treatment initiation before bacteriological cultures results. First line probabilistic treatment must have a bactericidal activity on the pathogens and must be atoxic. The empirical therapy consisted of ceftazidime 100 mg/k/d and vancomycine 40 mg/k/d three times a day. We treated 41 patients, ranged from 0.5 to 17 years (mean 9.5 years). 27 lymphoblastic leukaemias, 10 myeloblastic leukaemias, 4 lymphomas, presenting post therapeutic prolonged aplasia: PMN less than 500/mm3. 23 strains were isolated from 15 patients. 12 Gram+: 7 ceftazidime sensitive, 12 vancomycine sensitive and 11 Gram-: 10 ceftazidime sensitive. Only one is resistant to ceftazidime + vancomycine. Apyrexia was obtained in less than 48 hours in 36 patients. Mean treatment duration was 16 days. Hyperthermia relapsed 17 times and was susceptible to ampho B ten times, although no candida was isolated. When ceftazidime + vancomycine combination failed, other antibiotic treatment was ineffective. There were 4 superinfections (2 in blood, 1 enteric, 1 pharyngeal) and 2 germs were ceftazidime resistant. IN CONCLUSION: ceftazidime + vancomycine combination is a very effective treatment of infection in the neutropenic children: 88% success. 95% of the germs are sensitive to, at least, one of the 2 antibiotics. There are very few superinfections. Tolerance is excellent. PMID- 2200995 TI - [Ambulatory treatment with cefuroxime-axetil of infectious bronchitis in patients sixty years of age or older: comparative study of the combination of amoxicillin and clavulanic acid]. AB - The aim of this multicenter, prospective randomized trial was to compare the efficacy and safety of cefuroxime-axetil and amoxycillin/clavulanic acid for the treatment of infectious bronchitis in the elderly patient. Between January and April 1989, 157 out patients aged 60 years or more and presenting with infectious bronchitis were treated with either cefuroxime-axetil (250 mg bid), or the association amoxycillin/clavulanic acid (500 mg/125 mg bid). The two treatment groups were comparable at the time of inclusion; the mean age was 70 years, 82% of the patients were febrile, 75% presented purulent expectoration, 24% had a history of chronic bronchitis and 19% received symptomatic treatment was NSAIDs. The mean duration of treatment was 9 days. Clinical efficacy was assessed by the investigators. While fever and cough resolved similarly in the two groups, statistically fewer patients presented persistent purulent expectoration in the cefuroxime-axetil treatment group than in the group receiving amoxycillin/clavulanic acid (2% and 13%, respectively, p = 0.03). The proportion of patients who reported at least one side-effect was 3.6% in the cefuroxime axetil treatment group against 21.6% of those who received the association (p = 0.006). PMID- 2200997 TI - [Comparative study of two protocols of antibiotic prophylaxis in endoscopic urologic surgery]. AB - We report an open, prospective, randomized and double-blind study which compared two groups of patients without preoperative bacteriuria, undergoing transurethral urologic surgery. A first group received cefazoline 3 g perioperatively and a second group a single preoperative dose of cefotiam 1 g. A hundred patients were included in each group which were well matched on all essential characteristics, risk factors, surgery, anesthesia and postoperative temperature. The incidence of postoperative infection (bacteriemia and bacteriuria) was the same in both groups (16%). It is concluded that in transurethral urologic surgery performed in patients without preoperative bacteriuria, 1 preoperative dose cefotiam is as efficacious as 3 perioperative doses cefazoline. PMID- 2200998 TI - Vision/eye screening: test twice and refer once. PMID- 2200999 TI - The differential diagnosis of leukokoria. PMID- 2201000 TI - Retinoblastoma 1990: diagnosis, treatment, and implications. PMID- 2201001 TI - [Use of chlorbutin in the complex treatment of systemic forms of juvenile rheumatoid arthritis]. PMID- 2201002 TI - [Echinococcosis of the liver in children]. PMID- 2201003 TI - On some two-way barriers between models and mechanisms. AB - A number of recent as well as classic ideas suggest that there are constraints and limits on the explanatory role that computational, mathematical, and neural net models of visual and other cognitive processes can play that have not been generally appreciated. These ideas come from mathematics, automata theory, chaos theory, thermodynamics, neurophysiology, and psychology. Collectively, these ideas suggest that the neural or cognitive mechanisms underlying many kinds of formal models are untestable and unverifiable. Models may be good descriptions of perceptual and other cognitive processes, but they cannot in principle be reductive explanations nor can we use them to predict behavior at the molar level from what we know of the neural primitives. This discussion is an effort to clarify the appropriate meanings of these models, not to dissuade workers from forging ahead in the modeling endeavor, which I acknowledge is progressing and is making possible our increasingly deep appreciation of plausible and interesting cognitive processes. PMID- 2201004 TI - Vaginal birth. Normal delivery after caesarean section. PMID- 2201005 TI - An air of hope. PMID- 2201006 TI - Prostatein C3-mRNA: a sensitive marker of androgen-responsiveness in prostate explant cultures. AB - Prostatein is an androgen-dependent protein which is secreted by the rat ventral prostate. To determine if prostatein or its mRNA were responsive to androgen in vitro, prostate explants were cultured in media containing 0 or 25 nM dihydrotestosterone (DHT), estradiol (E2), or cortisol (F). Prostatein concentrations in medium were measured by radioimmunoassay at 2 and 4 days and in homogenates at 4 days. They were not changed significantly by any of these steroids. The concentration of the mRNA for the C3-subunit of prostatein was determined by dot hybridization at 0, 2, 4, 6, and 8 days. It was decreased significantly by 2 days when compared with explants cultured in the presence of DHT and significant differences persisted through 8 days. In conclusion, quantitation of the mRNA for the C3-subunit of prostatein in short-term cultures of ventral prostate explants appears to be more sensitive to changes in androgen concentration than does measurement of prostatein, per se. Prostatein C3-mRNA may be a useful marker for in vitro studies of androgen agonists and antagonists. PMID- 2201007 TI - Induction of chemical castration in male rats by a new long-acting LHRH antagonist. AB - LHRH-antagonists might represent a useful new type of androgen deprivation to treat prostatic cancer. In this context adult intact male rats were treated subcutaneously with different concentrations of the new LHRH-antagonist antide either once (1, 3, 6, 10, 15 mg/kg) or on 5 consecutive days (5 x 3 mg/kg). The effect on serum concentration of LH and testosterone and the effect on the weights of testes, prostate, and seminal vesicles was investigated after different periods of time (24 hours, 1, 2, 3, 5, and 8 weeks). Histological evaluation of the testes was also performed. A clear dose-dependent inhibitory effect on the above-mentioned parameters was observed. The most effective treatment schedule was the single application of 15 mg/kg resulting in castration like inhibition of prostate weights and marked inhibition of spermatogenesis within 2 weeks, which was maintained 8 weeks after the injection. Serum LH and serum testosterone concentrations were below the detection limit of the assay within 2 weeks and showed first signs of recovery after 8 weeks. Histologically, no signs indicative of irreversible effects (testes) were observed. To summarize, the LHRH-antagonist antide was found to have a profound long-lasting inhibitory but reversible effect on the reproductive system of adult intact male rats. These data emphasize the suitability of this type of compound for the treatment of prostatic cancer. PMID- 2201008 TI - To test or not to test in pediatric practice? PMID- 2201009 TI - Limb pain in childhood. PMID- 2201010 TI - Perinatal blood loss. PMID- 2201011 TI - Special infant formulas. PMID- 2201013 TI - Haemostasis in hypothyroidism. AB - Abnormalities that have been reported for platelet indices and function, coagulation factors and tests, and the fibrinolytic system in hypothyroidism are reviewed. These abnormalities, although usually of limited importance clinically, may occasionally lead to major bleeding episodes and to diagnostic confusion. PMID- 2201014 TI - Focal fatty infiltration of the liver mimicking metastatic disease. AB - We report the mistaken diagnosis of metastatic liver disease by ultrasonography in a patient with congestive heart failure and focal fatty infiltration of the liver. Multiple echogenic space-occupying lesions in the liver can be caused by benign conditions as well as tumour deposits and in a debilitated patient the possibility of focal fatty infiltration should always be considered. PMID- 2201012 TI - Cardiology. PMID- 2201015 TI - Hypoglycaemia in Sudanese children with cerebral malaria. PMID- 2201016 TI - Biosynthetic pathways of pteridines and their association with phenotypic expression in vitro in normal and neoplastic pigment cells from goldfish. AB - The distribution of GTP-cyclohydrolase I, pyruvoyl tetrahydropterin (dysopropterin) synthase, and pyruvoyl tetrahydropterin reductase in goldfish erythrophores, melanophores, and erythrophoroma cells in vitro has been revealed by specific biochemical assays. The activity of pyruvoyl tetrahydropterin synthase in the erythrophores is nearly the same as that in rat kidney and pineal gland. Results of the simultaneous quantification of unconjugated pteridines (biopterin, sepiapterin, neopterin, and pterin) by HPLC indicate that the total amounts of these derivatives present in these cells and in the respective culture media are closely correlated with the activities of these enzymes. These findings imply that these cells are capable of the autonomous synthesis of pteridines, which most likely proceeds from GTP to 6-lactoyl-5,6,7,8-tetrahydropterin (reduced sepiapterin), via dihydroneopterin triphosphate and pyruvoyl tetrahydropterin, through reactions catalyzed by these enzymes. A comparison of pteridine metabolism between clones of the stem cell type and the yellow pigmented clones induced from erythrophoroma cells suggests that brightly colored pigmentation involves two separate phases: the biosynthesis of pteridines and their deposition in the pigment organelles. The presence of the highly active pteridine-synthesizing enzymes in melanophores and melanogenic erythrophoroma cells strongly suggests a loose commitment to the expression of pigment phenotypes in this species. PMID- 2201017 TI - Postmortem pink teeth phenomenon: an experimental study and a survey of the literature. AB - The appearance of pink teeth after death is a phenomenon long familiar to forensic dentists. Although the application of modern techniques has shed some light on its aetiology, elucidation of the ultimate mechanism underlying the phenomenon is still awaited. In this paper, previous literature on the subject is surveyed, and an experimental approach under standardized conditions to allow analysis of possible causes and biological mechanisms of the pink-teeth phenomenon in rats is described. The experimental results were consistent with most previous observations. It seems probable that colouration of the teeth would be found in those regions of the jaws where the blood is seeking on the basis of gravitation hypostasis. The primary red colouration is most likely due to haemoglobin derivatives within the necrotic pulp tissue in cases in which blood has accumulated in the head and the dependent lividity (hypostasis) is obstructed. The authors discuss the likely causes for the development of the pink teeth phenomenon. It seems that this phenomenon is more dependent on physical than chemical factors after death. PMID- 2201018 TI - Broad spectrum of in vivo forward mutations, hypermutations, and mutational hotspots in a retroviral shuttle vector after a single replication cycle: substitutions, frameshifts, and hypermutations. AB - We determined the in vivo forward mutation rate in a single replication cycle for spleen necrosis virus (SNV). A method was developed to clone integrated proviruses of retroviral shuttle vectors by exploiting the tight binding of the lac operator to the lac repressor protein. The vectors contained the lacZ alpha gene as a reporter of mutations. Thirty-seven of the 16,867 proviruses recovered contained five classes of mutations, including substitutions and frameshifts. Runs of 9 and 10 identical base pairs and a direct repeat of 110 base pairs were mutational hotspots. In addition, two copies of a provirus contained 15 G-to-A substitutions. Such proviruses, which we name hypermutants, may arise through the action of an error-prone polymerase and could significantly contribute to the genetic variation in retroviral populations. PMID- 2201019 TI - Molecular characterization of the GCN4-DNA complex. AB - We report studies of the DNA complex formed by GCN4, a transcriptional activator of eukaryotic amino acid biosynthetic operons. The DNA thermodynamic binding domain, defined by primer extension analysis, spans at least 18 base pairs, a site much larger than the 9-base-pair consensus defined by homology with naturally occurring binding sites. Chemical modification experiments reveal multiple sites of protein-DNA contact: methylation of any guanine N-7 or adenine N-3, ethylation of any phosphate oxygen, or elimination of any nucleoside within a region spanning nearly one and a half turns of the double helix reduces the binding affinity of the complex measurably. Nevertheless, the protein yields no detectable hydroxyl radical footprint, implying that the minor groove is reagent accessible in the protein-DNA complex. These chemical modification patterns indicate that GCN4 does not utilize any of the DNA-recognition motifs of paradigm DNA-binding proteins. Assays to detect DNA bending induced by truncated or intact GCN4 indicate that protein conformation and not a protein-induced bend is responsible for the anomalous electrophoretic behavior of GCN4-DNA complexes. PMID- 2201020 TI - Single d(ApG)/cis-diamminedichloroplatinum(II) adduct-induced mutagenesis in Escherichia coli. AB - The mutation spectrum induced by the widely used antitumor drug cis diamminedichloroplatinum(II) (cis-DDP) showed that cisDDP[d(ApG)] adducts, although they account for only 25% of the lesions formed, are approximately 5 times more mutagenic than the major GG adduct. We report the construction of vectors bearing a single cisDDP[d(ApG)] lesion and their use in mutagenesis experiments in Escherichia coli. The mutagenic processing of the lesion is found to depend strictly on induction of the SOS system of the bacterial host cells. In SOS-induced cells, mutation frequencies of 1-2% were detected. All these mutations are targeted to the 5' base of the adduct. Single A----T transversions are mainly observed (80%), whereas A----G transitions account for 10% of the total mutations. Tandem base-pair substitutions involving the adenine residue and the thymine residue immediately 5' to the adduct occur at a comparable frequency (10%). No selective loss of the strand bearing the platinum adduct was seen, suggesting that, in vivo, cisDDP[d(ApG)] adducts are not blocking lesions. The high mutation specificity of cisDDP[d(ApG)]-induced mutagenesis is discussed in relation to structural data. PMID- 2201021 TI - Isolation and characterization of a Chinese hamster ovary cell line deficient in fatty alcohol:NAD+ oxidoreductase activity. AB - We have isolated a mutant Chinese hamster ovary cell line that is defective in long-chain fatty alcohol oxidation. The ability of the mutant cells to convert labeled hexadecanol to the corresponding fatty acid in vivo was reduced to 5% of the parent strain. Whole-cell homogenates from the mutant strain, FAA.1, were deficient in long-chain fatty alcohol:NAD+ oxidoreductase (FAO; EC 1.1.1.192) activity, which catalyzes the oxidation of hexadecanol to hexadecanoic acid, although the intermediate fatty aldehyde was formed normally. A direct measurement of fatty aldehyde dehydrogenase showed that the FAA.1 strain was defective in this component of FAO activity. FAA.1 is a two-stage mutant that was selected from a previously described parent strain, ZR-82, which is defective in ether lipid biosynthesis and peroxisome assembly. Because of combined defects in ether lipid biosynthesis and fatty alcohol oxidation, the ability of the FAA.1 cells to incorporate hexadecanol into complex lipids was greatly impaired, resulting in a 60-fold increase in cellular fatty alcohol levels. As the FAO deficiency in FAA.1 cells appears to be identical to the defect associated with the human genetic disorder Sjogren-Larsson syndrome, the FAA.1 cell line may be useful in studying this disease. PMID- 2201022 TI - Tissue-specific expression and methylation of a thyroglobulin-chloramphenicol acetyltransferase fusion gene in transgenic mice. AB - Fusion genes containing 1600 or 2000 base pairs of the bovine thyroglobulin gene 5' flanking region and the chloramphenicol acetyltransferase (CAT) coding sequence were constructed and used to generate transgenic mice. Altogether, 24 independent transgenic lines were obtained, and the expression of the transgene was assayed by measuring the CAT activity in different tissues. Depending on the transgenic lines, the fusion gene was either silent in all tissues or specifically expressed in the thyroid. The level of expression was found to be highly variable from one line to another and to be regulated by thyrotropin in a manner similar to the natural thyroglobulin gene. The methylation status of the integrated DNA was tested by digestion of DNA extracted from thyroid and other tissues with the isochizomers Msp I and Hpa II. It was found that one of the Hpa II sites was demethylated specifically in the thyroid. PMID- 2201023 TI - Mapping small DNA sequences by fluorescence in situ hybridization directly on banded metaphase chromosomes. AB - A procedure for mapping small DNA probes directly on banded human chromosomes by fluorescence in situ hybridization has been developed. This procedure allows for the simultaneous visualization of banded chromosomes and hybridization signal without overlaying two separate photographic images. This method is simple and rapid, requires only a typical fluorescence microscope, has proven successful with DNA probes as small as 1 kilobase, is applicable for larger probes, and will greatly facilitate mapping the vast number of probes being generated to study genetic disease and define the human genome. Human metaphase chromosomes were prepared from phytohemagglutinin-stimulated lymphocyte cultures synchronized with bromodeoxyuridine and thymidine. Probes were labeled with biotin-dUTP, and the hybridization signal was amplified by immunofluorescence. Chromosomes were stained with both propidium iodide and 4',6-diamidino-2-phenylindole (DAPI), producing R- and Q-banding patterns, respectively, allowing unambiguous chromosome and band identification while simultaneously visualizing the hybridization signal. Thirteen unique DNA segments have been localized to the long arm of chromosome 11 by using this technique, and localization of 10 additional probes by using radioactive in situ hybridization provides a comparison between the two procedures. These DNA segments have been mapped to all long-arm bands on chromosome 11 and in regions associated with neoplasias and inherited disorders. PMID- 2201024 TI - Genetic evidence for an interaction between SIR3 and histone H4 in the repression of the silent mating loci in Saccharomyces cerevisiae. AB - Repression of transcription from the silent mating loci (HML alpha and HMRa) is essential for mating ability in Saccharomyces cerevisiae. This silencing is known to require at least five proteins (SIR1, SIR2, SIR3, SIR4, and histone H4) and is accompanied by a change in chromatin structure. We show here that four positions of histone H4 (N-terminal residues 16, 17, 18, and 19) are crucial to silencing. HML alpha and HMRa are efficiently repressed when these positions are occupied by basic amino acids but are derepressed when substituted with glycine. These results suggest that acetylation of Lys-16 would lead to derepression of the silent mating loci. Three strong extragenic suppressors of the latter H4 mutations were isolated and determined to be located in SIR3. These suppressors allow high mating efficiencies in cells expressing either wild-type H4 or H4 containing single amino acid substitutions. They did not allow efficient mating in a strain that contained an H4 N-terminal deletion. These results indicate that the SIR3 mutations do not bypass the requirement for the H4 N terminus but, rather, allow repression in the presence of a less than optimal H4 N terminus. This provides a link between one of the SIR proteins and a component of chromatin. PMID- 2201026 TI - Evolution of spatial cognition: sex-specific patterns of spatial behavior predict hippocampal size. AB - In a study of two congeneric rodent species, sex differences in hippocampal size were predicted by sex-specific patterns of spatial cognition. Hippocampal size is known to correlate positively with maze performance in laboratory mouse strains and with selective pressure for spatial memory among passerine bird species. In polygamous vole species (Rodentia: Microtus), males range more widely than females in the field and perform better on laboratory measures of spatial ability; both of these differences are absent in monogamous vole species. Ten females and males were taken from natural populations of two vole species, the polygamous meadow vole, M. pennsylvanicus, and the monogamous pine vole, M. pinetorum. Only in the polygamous species do males have larger hippocampi relative to the entire brain than do females. Two-way analysis of variance shows that the ratio of hippocampal volume to brain volume is differently related to sex in these two species. To our knowledge, no previous studies of hippocampal size have linked both evolutionary and psychometric data to hippocampal dimensions. Our controlled comparison suggests that evolution can produce adaptive sex differences in behavior and its neural substrate. PMID- 2201025 TI - Human immunodeficiency virus type 1 protease cleaves the intermediate filament proteins vimentin, desmin, and glial fibrillary acidic protein. AB - The intermediate filament proteins vimentin, desmin, and glial fibrillary acidic protein are cleaved in vitro by human immunodeficiency virus type 1 protease (HIV 1 PR). Microsequencing showed that HIV-1 PR cleaved both human and murine vimentin between leucine-422 and arginine-423 within the sequence between positions 418 and 427, Ser-Ser-Leu-Asn-Leu/Arg-Glu-Thr-Asn-Leu (SSLNL/RETNL). Minor cleavages at other sites were also observed. Heat-denatured vimentin was cleaved by HIV-1 PR less efficiently than native vimentin. A decapeptide containing the sequence SSLN-LRETNL was also cleaved in vitro by HIV-1 PR as predicted. The presence of a charged residue (arginine) at the primary cleavage site distinguishes this from other known naturally occurring cleavage sites. Microinjection of HIV-1 PR into cultured human fibroblasts resulted in a 9-fold increase in the percentage of cells with an altered and abnormal distribution of vimentin intermediate filaments. Most commonly, the intermediate filaments collapsed into a clump with a juxtanuclear localization. These results support the possibility that intermediate filament proteins may serve as substrates within HIV-1-infected cells. PMID- 2201027 TI - cDNA sequence analysis of a 29-kDa cysteine-rich surface antigen of pathogenic Entamoeba histolytica. AB - A gamma gt11 cDNA library was constructed from poly(U)-Sepharose-selected Entamoeba histolytica trophozoite RNA in order to clone and identify surface antigens. The library was screened with rabbit polyclonal anti-E. histolytica serum. A 700-base-pair cDNA insert was isolated and the nucleotide sequence was determined. The deduced amino acid sequence of the cDNA revealed a cysteine-rich protein. DNA hybridizations showed that the gene was specific to E. histolytica since the cDNA probe reacted with DNA from four axenic strains of E. histolytica but did not react with DNA from Entamoeba invadens, Acanthamoeba castellanii, or Trichomonas vaginalis. The insert was subcloned into the expression vector pGEX-1 and the protein was expressed as a fusion with the C terminus of glutathione S transferase. Purified fusion protein was used to generate 22 monoclonal antibodies (mAbs) and a mouse polyclonal antiserum specific for the E. histolytica portion of the fusion protein. A 29-kDa protein was identified as a surface antigen when mAbs were used to immunoprecipitate the antigen from metabolically 35S-labeled live trophozoites. The surface location of the antigen was corroborated by mAb immunoprecipitation of a 29-kDa protein from surface-125I labeled whole trophozoites as well as by the reaction of mAbs with live trophozoites in an indirect immunofluorescence assay performed at 4 degrees C. Immunoblotting with mAbs demonstrated that the antigen was present on four axenic isolates tested. mAbs recognized epitopes on the 29-kDa native antigen on some but not all clinical isolates tested. PMID- 2201029 TI - Peptides on phage: a vast library of peptides for identifying ligands. AB - We have constructed a vast library of peptides for finding compounds that bind to antibodies and other receptors. Millions of different hexapeptides were expressed at the N terminus of the adsorption protein (pIII) of fd phage. The vector fAFF1, derived from the tetracycline resistance-transducing vector fd-tet, allows cloning of oligonucleotides in a variety of locations in the 5' region of gene III. A library of 3 x 10(8) recombinants was generated by cloning randomly synthesized oligonucleotides. The library was screened for high-avidity binding to a monoclonal antibody (3-E7) that is specific for the N terminus of beta endorphin (Tyr-Gly-Gly-Phe). Fifty-one clones selected by three rounds of the affinity purification technique called panning were sequenced and found to differ from previously known ligands for this antibody. The striking finding is that all 51 contained tyrosine as the N-terminal residue and that 48 contained glycine as the second residue. The binding affinities of six chemically synthesized hexapeptides from this set range from 0.35 microM (Tyr-Gly-Phe-Trp-Gly-Met) to 8.3 microM (Tyr-Ala-Gly-Phe-Ala-Gln), compared with 7.1 nM for a known high affinity ligand (Tyr-Gly-Gly-Phe-Leu). These results show that ligands can be identified with no prior information concerning antibody specificity. Peptide libraries are also likely to be useful in finding ligands that bind to other classes of receptors and in discovering pharmacologic agents. PMID- 2201028 TI - Cooperation between two growth factors promotes extended self-renewal and inhibits differentiation of oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells. AB - Bipotential oligodendrocyte-type-2 astrocyte (O-2A) progenitor cells, which give rise to oligodendrocytes and type-2 astrocytes in cultures of rat optic nerve, are one of the few cell types in which most aspects of proliferation and differentiation can be manipulated in a defined in vitro environment. Previous studies have shown that O-2A progenitors exposed to platelet-derived growth factor (PDGF) divide as migratory bipolar cells a limited number of times, with a cell cycle time of 18 hr, before clonally related progenitors differentiate into nondividing oligodendrocytes with a timing similar to that seen in vivo. In contrast, O-2A progenitors grown in the absence of mitogen do not divide but instead differentiate prematurely into oligodendrocytes, and progenitors exposed to appropriate inducing factors differentiate into type-2 astrocytes. We now have found that O-2A progenitors can be induced to undergo continuous self-renewal in the absence of oligodendrocytic differentiation by exposure to a combination of PDGF and basic fibroblast growth factor (bFGF). With the exception of the inhibition of differentiation, the O-2A progenitors exposed to PDGF and bFGF behaved similarly to those exposed to PDGF alone. In contrast, progenitors exposed to basic bFGF alone were multipolar, had a cell-cycle length of 45 hr, showed little migratory behavior, underwent premature oligodendrocytic differentiation, and did not cease division upon expression of oligodendrocyte marker antigens. Thus, inhibition of differentiation required the presence of both mitogens. Our results demonstrate that PDGF and bFGF act on O-2A progenitors as both inducers of division and as regulators of differentiation that modulate multiple aspects of O-2A progenitor development and, additionally, reveal a previously unrecognized means of regulating self-renewal processes, wherein cooperation between growth factors promotes continuous division in the absence of differentiation. PMID- 2201030 TI - Isolation and expression of rat liver sepiapterin reductase cDNA. AB - Sepiapterin reductase (7,8-dihydrobiopterin: NADP+ oxidoreductase, EC 1.1.1.153) catalyzes the terminal step in the biosynthetic pathway for tetrahydrobiopterin, the cofactor necessary for aromatic amino acid hydroxylation. We report here the isolation of a cDNA clone for rat liver sepiapterin reductase. The cDNA has been excised from a lambda vector and the DNA sequence was determined. The insert contains the coding sequence for at least 95% of the rat enzyme and is fused to the Escherichia coli beta-galactosidase N-terminal segment and the lac promoter. The N-terminal region of the clone contains an extraordinarily high G + C content. The amino acid sequence deduced from the clone is in agreement with the size and composition of the enzyme and was matched to several tryptic peptide sequences. The enzyme encoded by the cDNA insert was shown to have sepiapterin reductase activity after expression in E. coli. Structural similarities were identified between this protein and several enzymes that should contain similar nucleotide and pteridine binding sites. PMID- 2201032 TI - Is there a rationale for large lymphadenectomy in adenocarcinoma of the kidney? PMID- 2201033 TI - Metastasis of renal-cell carcinoma: a pathologist's theoretical view. PMID- 2201031 TI - An endogenous lectin and one of its neuronal glycoprotein ligands are involved in contact guidance of neuron migration. AB - In the central nervous system, postmitotic neurons migrate along astrocytic processes to reach their adult position. The molecular mechanisms of this guided migration are not clearly defined, although some steps have been shown to involve proteases and cell adhesion molecules. We report that monovalent antibodies (Fab fragments) raised against an endogenous cerebellar soluble lectin (CSL) completely inhibit neuronal migration in cultures of cerebellar explants at concentrations as low as 50 micrograms/ml. A similar inhibition pattern was obtained with Fab fragments prepared against one of the endogenous glycoprotein ligands of CSL, the 31-kDa glycoprotein (this glycoprotein is a membrane-bound glycoprotein specifically occurring, in the cerebellum, at the surface of immature neurons). We propose that this lectin-glycoprotein interaction supports the adhesion between neurons and the astrocyte guide during the migration of cerebellar immature neurons. PMID- 2201034 TI - Interferon-alpha and interleukin-2 in the treatment of renal cell cancer. PMID- 2201035 TI - Can oxysterols have some interest in the treatment of tumors? PMID- 2201036 TI - Cancer immunotherapy with autologous and allogeneic vaccines: a practical overview. PMID- 2201037 TI - The impact of chemotherapy on the survival of patients with metastatic urothelial tumors. PMID- 2201038 TI - The evolution of active chemotherapy in metastatic and locally advanced bladder cancer. PMID- 2201039 TI - Overview of hormonal therapy for prostate cancer. PMID- 2201040 TI - The importance of pretreatment testosterone and other prognostic variables in the response to androgen deprivation therapy. PMID- 2201041 TI - Is there a role for pure antiandrogens in the treatment of advanced prostatic cancer? AB - Our preliminary experience shows that flutamide is an effective treatment in patients with stage C and D prostate cancer. Local and distant response rates appear to be comparable with those obtained by "classic" hormone therapy. Libido and sexual potency are generally not affected. Palliation of symptoms is frequent and is usually accompanied by improvement of performance status and quality of life. The side effects are slight or moderate, but an elevation of transaminases in patients with borderline liver insufficiency is possible. PMID- 2201043 TI - Weekly chemotherapeutic regimen in metastatic prostate cancer. AB - 1. A weekly fractionation of EPIRUBICIN at an unchanged dose intensity leads to a significant decrease in toxicity. 2. The weekly administration of 25 mg/m2 EPIRUBICIN is effective in treating hormone refractory prostate carcinoma and completely fulfills the requirements for palliation. PMID- 2201042 TI - Chemotherapy of advanced cancer of the prostate. PMID- 2201044 TI - Systemic treatment for renal cell carcinoma: an overview. PMID- 2201045 TI - Phase II cytotoxic chemotherapy trials in renal cell carcinoma: 1983-1988. PMID- 2201046 TI - Immune modifiers in the treatment of bladder cancer. PMID- 2201047 TI - Overview of systemic treatment of bladder cancer and results with M-VAC therapy. AB - Cytotoxic chemotherapy is playing an increasingly important role for advanced disease, and is being properly evaluated in prospective trials as neoadjuvant therapy. There has been no major undertaking to examine adjuvant treatment, and hopefully randomized studies will be started in the future. There is sparse data concerning the effectiveness of immunological agents for treatment of this tumor, and phase II efficacy studies are needed. Future studies will need to define more accurately the poor-risk group in whom new agents or regimens using a more intensive schedule, perhaps with G-CSF, can be explored as initial therapy. PMID- 2201048 TI - Abnormal feeding behavior and insulin replacement in STZ-induced diabetic rats. AB - The present studies were undertaken to investigate whether or not decreased ambulatory activity, including abnormal feeding behavior in diabetic rats, will be simultaneously normalized by insulin administration. To do this, we used the Gunma University-type automatic apparatus for continuous and direct measurement of ambulation and drinking. In this study, 3 U NPH insulin were administered at 1800, just before the dark phase, and 2 U were administered at 0600, just before the light phase. With these insulin doses, we found that 5 weeks were needed to normalize ambulatory activity, 4 weeks were necessary for food intake, 6 weeks for drinking and 2 weeks for body weight. Since ambulatory activity is reported to be related to changes in dopamine turnover, further studies are in progress to determine whether or not dopamine turnover is normalized when there is no difference in ambulatory activity due to insulin replacement. PMID- 2201049 TI - Finding the base of the brain. AB - An electrode carrier mounted in a T-slot holder is described. An electronic circuit detects the vertical displacement of the carrier in the T-slot when an electrode encounters the base of the skull. Use of this vertical coordinate can reduce errors in locating structures at or close to the base of the brain. PMID- 2201050 TI - The role of emergent exploration in free-tissue transfer: a review of 150 consecutive cases. AB - One-hundred and fifty consecutive free-tissue transfers were reviewed to evaluate the role of emergent exploration in flap survival. Eleven flaps exhibited signs of circulatory failure between 1 hour and 6 days postoperatively and required return to the operating room. In eight patients the preoperative diagnosis was venous thrombosis, and in three patients it was arterial thrombosis. The average time from the first abnormal examination to exploration was 1.5 hours. There were no false-positive explorations. All 11 flaps were salvaged following correction of the cause of circulatory compromise. In eight patients this was due to inflow or outflow obstruction in the recipient vessels proximal to the anastomosis, in two patients it was due to extrinsic compression of the flap from a tight wound closure, and in one patient it was due to obstruction of the recipient vein by a drain. Primary anastomotic thrombosis was not encountered as the cause of circulatory compromise in any patient. An aggressive approach to exploration was responsible for an increase in flap survival in the entire series from 90 to 98 percent. The results of this study demonstrate the efficacy of clinical monitoring, the role of early exploration, and the durability of microvascular anastomoses. PMID- 2201051 TI - Ultraviolet light and free radicals: an immunologic theory of epidermal carcinogenesis. PMID- 2201052 TI - Dictionary of mental health programs: a response to a fragmented mental health system. PMID- 2201053 TI - Using fiscal data to identify heavy service users. PMID- 2201054 TI - Metabolic rate depression and biochemical adaptation in anaerobiosis, hibernation and estivation. AB - For many animals, the best defense against harsh environmental conditions is an escape to a hypometabolic or dormant state. Facultative metabolic rate depression is the common adaptive strategy of anaerobiosis, hibernation, and estivation, as well as a number of other arrested states. By reducing metabolic rate by a factor ranging from 5 to 100 fold or more, animals gain a comparable extension of survival time that can support months or even years of dormancy. The present review focuses on the molecular control mechanisms that regulate and coordinate cellular metabolism for the transition into dormancy. These include reversible control over the activity state of enzymes via protein phosphorylation or dephosphorylation reactions, pathway regulation via the association or dissociation of particle-bound enzyme complexes, and fructose-2,6-bisphosphate regulation of the use of carbohydrate reserves for biosynthetic purposes. These mechanisms, their interactions, and the regulatory signals (e.g., second messenger molecules, pH) that coordinate them form a common molecular basis for metabolic depression in anoxia-tolerant vertebrates (goldfish, turtles) and invertebrates (marine molluscs), hibernation in small mammals, and estivation in land snails and terrestrial toads. PMID- 2201055 TI - Steps towards cancer therapy with radionuclides--a review including radiation biophysical aspects. AB - Though great advantages will be connected with endoradiotherapy, a lot of problems has still to be overcome, the greatest of them being without doubt the problem of selectivity of the carrier compounds. Some few of them have proved to be able to accumulate in certain cancers by reason of their incorporation as metabolites, especially in melanomas. The other great hope are the monoclonal antibodies or their fragments, and in this field much endeavour has been spent in the last years. Especially the two-step method of loading the radioactive nuclide to the antibodies when their binding to the cancer cells is complete appears very promising. Some other, unspecific vehicles may also prove suitable for accumulation in certain tumor types. For the selection of the nuclides it has to be considered that radiation biophysical experiments demonstrated that the critical targets for radiation action are with high probability the DNA superstructure units, and that the distribution of ionizations within them is decisive for the inactivation of a cell. With sparsely ionizing radiation (e.g. beta-radiation) rather high doses are required for reaching an adequate concentration of ionizations in these DNA units. Densely ionizing radiation with an LET of about 150 keV/microns exhibits the maximum relative biological effectiveness (12-16 referred to X-radiation). Therefore emitters of alpha particles the LET of which lies actually somewhat lower, near 100 keV/microns, seem to be very suitable for endoradiotherapy. Moreover the short ranges of these particles (about 60 microns in tissue) render an extensive sparing of the surrounding normal tissue possible. The second group of effective nuclides is that of Auger electron emitters. The low-energy proportion of Auger electrons leads to a high ionization density in small volumes. The very short ranges of these electrons (in the nanometer range), however, require an incorporation of the nuclide into the cell nucleus if an effective cell inactivation is to occur. 211At (alpha-emitter) and 125I (Auger electron emitter) already proved their high inactivating effectiveness in cell cultures and their curative action in animal experiments, and studies of binding 211At to monoclonal antibodies are encouraging. Some other approaches proposed for the transport of radionuclides into tumor cells or for generating them within tumor tissue are also aimed in essential at the release of densely ionizing alpha-particles or of Auger electrons. PMID- 2201056 TI - Long term effects of monthly low dose whole body irradiation on the glutathione status and thiobarbituric acid-reactive substances in different organs of male Wistar rats. AB - Male Wistar-H-rats were exposed monthly to a 60cobalt-source low dose whole body irradiation (0.25 Gy, total dose: 4.5 Gy). The glutathione disulphide:total glutathione ratio, the concentration of thiobarbituric acid-reactive substances and the activities of glutathione peroxidase and glutathione transferase in eight different organs and blood were analysed. The low dose irradiation is accompanied by distinct peroxidative changes in organs. These oxidative loadings occur in the small intestine, the spleen and the kidneys. The measurements of glutathione status and of thiobarbituric acid-reactive substances are proposed as sensitive parameters for low dose radiation induced changes. PMID- 2201057 TI - Efficacy of 2-mercaptopropionylglycine (MPG): a radioprotector in modifying the gonadal response of whole body irradiated male Swiss albino mice. AB - Six week old male Swiss albino mice taken from an inbred colony were irradiated with 0.6 and 1.2 Gy of low 60Co gamma rays in the presence (Experimental) and absence (Control) of MPG. Results indicated the infliction of radiation insult and subsequent repair in the testes to be dose dependent, that is higher the dose greater the damage and sluggish the reparative activity. A greater number of surviving germ cells in the experimental tests with fewer dead cells reflected the protective efficiency of the drug against radiation damage to the cell population. Thus MPG not only protects against radiation induced cell death and depletion but also changes the mitotic rate of the stem cells by which an accelerated recovery was brought about. PMID- 2201059 TI - Germ cell-Sertoli cell interactions. AB - The interactions between the Sertoli cells and germ cells are progressively becoming an important part of testicular physiology. This paper explores the cytological basis for these interactions, detailing the cyclic changes in the Sertoli cells in concert with the stages of the seminiferous cycle and the nature of the blood-testis barrier. These cytological changes are correlated with a number of variations in the function of Sertoli cells. The mechanisms by which germ cells and Sertoli cells interact are explored and can be divided into those using cell-to-cell contact and others utilizing paracrine factors. PMID- 2201058 TI - Interactions between the seminiferous tubules and Leydig cells of the testis. PMID- 2201060 TI - Mesenchymal (stromal)-epithelial cell interactions in the testis and ovary which regulate gonadal function. PMID- 2201061 TI - Neurohypophysial peptides in the gonads: are they real and do they have a function? PMID- 2201062 TI - Intragonadal regulation of immune system functions. AB - Immune responses within the mammalian gonads, and in particular the testis, are deficient in spite of adequate lymphatic drainage and the presence of lymphocytes and MHC II+ macrophages. There is considerable evidence from in vivo and in vitro studies that this 'suppression' of the immune system may be due, at least in part, to localized inhibition or regulation of normal lymphocyte and/or macrophage functions within the gonads. In the testis, both steroidal and non steroidal products of the Leydig cells, including androgens, endorphins, and inhibin-related proteins, have been implicated in mediating this activity. In turn, a number of immune cell cytokines affect steroidogenic cell function in vitro. The studies described in this paper indicated that [3H]-thymidine incorporation by adult rat thymocytes in vitro was inhibited by conditioned medium collected from short-term incubations of Percoll-purified adult rat Leydig cells, but stimulated by testicular interstitial fluid and by conditioned medium collected from short-term incubations of adult rat seminiferous tubules. The factors responsible for these effects on thymocyte function appeared to be of large molecular weight, as they were retained by ultrafiltration membranes with exclusion limits of 10,000 or 30,000 daltons. It is hypothesized that an 'immunosuppressive' mechanism, principally mediated by non-steroidal factors secreted by the steroidogenic cells of the gonadal interstitial tissue, exists within the gonads in order to prevent activation of the immune system by germ cell antigens and growth factors associated with germ cell proliferation and differentiation. This mechanism probably acts in parallel with normal antigen specific tolerance mechanisms operating at the gonadal level. As immune responses to germ cells are believed to be a significant causative factor in infertility, particularly in men, this represents an important area for further study. PMID- 2201063 TI - Cell-cell communication in corpora lutea. PMID- 2201064 TI - Local control of testicular fluids. PMID- 2201065 TI - Infection due to Leuconostoc species: six cases and review. AB - Leuconostocs, members of the family Streptococcacae, have only recently been recognized as potential pathogens. We describe six cases of leuconostoc bacteremia and review 11 additional cases of infection reported in the literature. Fifteen patients with bacteremia ranged from neonates to persons aged 78 years. Almost all were hospitalized with significant underlying diseases, had received previous antibiotic therapy, and had undergone procedures that interrupted the normal integumentary defense. Leuconostoc bacteremia was associated with fever, leukocytosis, and gastrointestinal complaints. Eight of 15 patients had polymicrobial bacteremia, seven of these eight with staphylococcal species. Clinical isolates of Leuconostoc were frequently misidentified, usually as viridans streptococci. All clinical isolates identified to date--and most agricultural isolates--demonstrate a high level of resistance to vancomycin. Successful regimens for treatment of Leuconostoc include high-dose penicillin, clindamycin, and where appropriate, removal of infected intravascular catheters. Susceptibility testing of all gram-positive bacteria isolated from normally sterile body sites is recommended. PMID- 2201066 TI - Bacteremic disease due to Haemophilus influenzae capsular type f in adults: report of five cases and review. AB - Five cases of bacteremic infections due to Haemophilus influenzae type f in adults are described, and previous reports of type f disease in nonpediatric patients are reviewed. Respiratory tract infections were most common in our series (two cases of pneumonia, one of epiglottitis, and one of nosocomial septicemia probably resulting from aspiration pneumonitis). All of these patients had factors predisposing them to respiratory tract infections, e.g., neurologic disease, congestive heart failure, or cigarette smoking. A fifth patient, who was bacteremic without an apparent primary focus, had dysgammaglobulinemia. Six episodes of bacteremia occurred in five patients; 11 of 13 cultures of blood obtained before parenteral antibiotic therapy were positive. All isolates were biotype I and susceptible to ampicillin. Antibiotic therapy was curative in cases of proved respiratory tract infection but failed in the setting of nosocomial septicemia, perhaps because of delayed initiation. The brevity of antibiotic treatment of the cryptogenic bacteremia permitted infection of a prosthetic vascular graft and recurrent bacteremia. Graft removal and repeated antibiotic therapy were curative. PMID- 2201068 TI - Klebsiella pulmonary infections: occurrence at one medical center and review. AB - Klebsiella pneumoniae is the species of aerobic gram-negative bacteria most commonly recognized as a cause of community-acquired pneumonia. The vast majority of articles concerning the epidemiology, frequency, and clinical and radiographic features of community-acquired pneumonias caused by this organism are over 20 years old. Experience with community-acquired pneumonias due to K. pneumoniae at one medical center over the last 20 years is reported and compared with the previously published literature. The recent experience at Parkland Memorial is quite similar to that in the literature. Salient features include the infrequency of K. pneumoniae as a cause of community-acquired pneumonia, the lack of specificity and sensitivity of most clinical and radiographic findings, and the similarity to and potential confusion with anaerobic pneumonitis and cavitary lung disease if only expectorated sputums are utilized for diagnosis in certain population groups such as alcoholics. PMID- 2201067 TI - Opportunistic infections with Strongyloides stercoralis in renal transplantation. AB - Opportunistic infections with the nematode Strongyloides stercoralis occur most often in patients with impaired T lymphocyte function, including recipients of renal allografts. Occult intestinal infection can remain quiescent for more than 30 years, becoming apparent only after the initiation of immunosuppression. Pulmonary and gastrointestinal symptoms predominant as initial clinical manifestations in patients with strongyloides hyperinfection or dissemination. Although thiabendazole remains the treatment of choice for all forms of strongyloidiasis, the duration of therapy must be individualized on the basis of frequent examinations of both stool and sputum. Transplantation centers drawing patients from areas with endemic Strongyloides should evaluate potential recipients closely for occult strongyloides infection prior to initiating immunosuppressive therapy. Empiric therapy with thiabendazole should be considered for renal allograft recipients with unexplained eosinophilia and a history of travel or residence in an area with endemic Strongyloides. Prophylactic monthly administration of thiabendazole in immunocompromised patients who have survived strongyloides hyperinfection or dissemination can prevent reinfection. PMID- 2201069 TI - Infectious diseases of geriatric inmates. AB - The number of geriatric inmates is rapidly growing because of more frequent incarceration of older offenders as the number of the elderly in the general population increases nationally. The increase is also due to recent changes in sentencing patterns (e.g., longer sentences and tightened parole) that affect younger, long-term inmates. Geriatric inmates often have chronic medical illnesses that may result in hospitalization for infectious complications. These infectious conditions may be related to factors such as institutionalization (e.g., tuberculosis and influenza), chronic medical illness (e.g., pneumococcal pneumonia), and a history of alcohol or drug use (e.g., hepatitis B virus and retrovirus infection). The epidemiology of these conditions is reviewed. Since infectious complications among geriatric inmates will add stress to a correctional health care system that is already burdened by inmates with AIDS related illnesses, clinical recognition of these complications and preventive measures are of great importance. PMID- 2201070 TI - Syphilis serology in human immunodeficiency virus-infected patients with symptomatic neurosyphilis: case report and review. AB - The clinical and serologic diagnosis of syphilis in the human immunodeficiency virus-infected patient may be difficult to make. We have recently seen a case of symptomatic neurosyphilis in such a patient presenting with positive serum and CSF syphilis serology. On the basis of this case and similar cases reported in the literature, we conclude that most, if not all, human immunodeficiency virus infected patients with symptomatic neurosyphilis will have an elevated serum and CSF syphilis serology. However, experience with additional cases will be necessary in order to validate this conclusion. PMID- 2201071 TI - Zidovudine intolerance. AB - Patients may be intolerant of zidovudine for several reasons, the most prominent being hematologic toxicity. In vitro studies demonstrate that zidovudine is toxic to the myeloid and erythroid precursors in the bone marrow; at concentrations of zidovudine near those associated with the optimal antiviral effect in vitro, the proliferative capability of these progenitor cells is reduced 50%-70%. The clinical manifestations of anemia and leukopenia generally are time- and dose dependent. Strategies for alleviating the hematologic toxicity of zidovudine include the use of hematopoietic growth factors, such as erythropoietin, granulocyte colony-stimulating factor, or granulocyte-macrophage colony stimulating factor. Myopathy, a recently recognized toxic effect of zidovudine, also appears to be time-dependent. Patients often complain of muscle weakness and discomfort and exhibit an associated elevation in creatine phosphokinase level; dose reduction or discontinuation of therapy generally is required. Some patients have experienced high fever, nausea, and vomiting; however, these effects are unusual and of unclear etiology. The substantial proportion of patients with AIDS or AIDS-related complex receiving zidovudine who experience hematologic or muscular toxicity may benefit from treatment with new antiviral agents, such as dideoxyinosine, with toxicity profiles different from that of zidovudine. PMID- 2201073 TI - Considerations for the evaluation of antiretroviral agents in infants and children infected with human immunodeficiency virus: a perspective from the National Cancer Institute. AB - Human immunodeficiency virus (HIV) infection in infants and young children differs in a number of ways from that in adults. In most HIV-infected children the infection is acquired perinatally and the course of infection is more accelerated than in adults. Diseases related to B cell defects and dysgammaglobulinemia (e.g., multiple or recurrent bacterial infections) predominate early in the disease, and children can be symptomatic before their CD4+ count decreases. Lymphoid interstitial pneumonitis occurs frequently and almost exclusively in children, and a number of the opportunistic infections (e.g., cryptococcosis, toxoplasmosis) or malignancies (e.g., Kaposi's sarcoma) occur infrequently in children. A major disease manifestation in the pediatric population is HIV encephalopathy, which results in impairment in neurologic development that can lead to loss or lack of developmental milestones and to diminished intellectual function. The methodology and design of clinical trials for the study of pediatric HIV infection should consider these clinical and laboratory manifestations as well as the developmental differences that reflect the disease in infants and young children. PMID- 2201072 TI - Zidovudine resistance of human immunodeficiency virus. AB - The observation that human immunodeficiency virus resistant to zidovudine can be isolated from patients with AIDS or AIDS-related complex during prolonged zidovudine treatment was made with a plaque reduction assay employing a CD4 expressing HeLa cell line. Fifty percent inhibitory concentrations of zidovudine for isolates from untreated patients ranged from 0.01 to 0.05 microM. In contrast, most isolates from these patients showed decreased sensitivity after 6 months or more of zidovudine administration. Isolates from several patients showed progressive, stepwise reductions in sensitivity. Zidovudine-resistant isolates exhibited cross resistance to 3'-azido-2',3'-dideoxyuridine and 3'-azido 2',3'-dideoxyguanosine but not to dideoxycytidine, dideoxyinosine, foscarnet (phosphonoformate), or several other compounds. The clinical implications of these findings have yet to be determine. Studies are in progress to assess sensitivity patterns of isolates from patients who are at earlier stages of human immunodeficiency virus disease or who are receiving other drug therapy and to characterize the mutations and mechanisms accounting for resistance. PMID- 2201074 TI - Treatment of chancroid, 1989. AB - Since recommendations for the treatment of chancroid were made in 1985, in vitro and in vivo data indicate that the two drugs recommended, erythromycin (500 mg four times a day for 7 days) and ceftriaxone (250 mg intramuscularly in a single dose), remain effective. The alternative therapies of trimethoprim sulfamethoxazole (160/800 mg twice a day for 7 days) and amoxicillin-clavulanic acid (500/125 mg three times a day for 7 days) also appear to be effective, although there has been little experience with these drugs in the United States. Single-dose trimethoprim-sulfamethoxazole (640/3,200 mg) now lacks the efficacy of other regimens. The experience with ciprofloxacin (500 mg twice a day for 3 days) has been favorable, and other quinolones may prove useful. Concurrent infection with human immunodeficiency virus appears to result in an increased rate of failure of treatment for chancroid, and such cases may require more prolonged therapy. PMID- 2201075 TI - Treatment of syphilis, 1989. AB - With the introduction of penicillin after World War II, the incidence of syphilis in the United States decreased. Because of penicillin's great success, clinical trials stopped after an initial period of intensive investigation. Syphilis is a difficult disease to study; the natural history may span decades in an individual, and diagnosis and outcome are usually defined serologically, not clinically or bacteriologically. Although the recommended penicillin regimens changed, clinical trials were not repeated. Furthermore, because the early studies occurred before modern clinical-trial methodology was developed, interpretation of the results is difficult. As a result, while current regimens for syphilis therapy are effective, they may or may not be optimal. With the accumulation of reports of treatment failures and the recent appearance of human immunodeficiency virus, current regimens for the treatment of syphilis are being questioned. As background for a meeting at which treatment guidelines were reviewed, the available literature on syphilis therapy is summarized herein. PMID- 2201076 TI - Treatment of Chlamydia trachomatis genital infection. AB - Chlamydia trachomatis infections are the most frequent bacterial sexually transmitted diseases in the United States, with an estimated 4 million cases occurring annually. The mainstay of treatment for chlamydial infections has been the tetracyclines. Doxycycline, comparable in cost to tetracycline and with a less frequent dosage schedule, is the drug of first choice. Erythromycins are the drugs of choice for infections in pregnant women, nursing mothers, infants, children, and adults unable to tolerate tetracyclines. beta-Lactam antibiotics have had variable efficacy against C. trachomatis infections, although recent studies suggest that amoxicillin may be an effective alternative for C. trachomatis infection during pregnancy. Quinolones are currently being tested and may be used in alternative regimens in the future. The effectiveness of current antimicrobial regimens in preventing long-term complications of chlamydial infections should be determined in research studies. PMID- 2201077 TI - Pelvic inflammatory disease: review of treatment options. AB - Decisions regarding appropriate antibiotic therapy for treatment of pelvic inflammatory disease (PID) are complicated by an incomplete understanding of the syndrome. Further, the lack of data on laparoscopic diagnosis and cure of PID severely limits our ability to interpret data on therapy outcome. Validation studies of the treatment regimens recommended by the Centers for Disease Control in the 1985 treatment guidelines for sexually transmitted diseases (STDs) suggest that both the cefoxitin/doxycycline and clindamycin/aminoglycoside combination regimens result in consistently high rates of clinical evidence of cure. The 1989 STD treatment guidelines were based on these studies and on available data regarding newer treatment regimens. Empiric, broad-spectrum therapy remains the treatment of choice. The two regimens recommended for inpatient therapy in 1989 are similar to those recommended in 1985. The recommendation for management of ambulatory patients has been substantially changed, however, because of increasing resistance of Neisseria gonorrhoeae to penicillin. PMID- 2201078 TI - Treatment of sexually transmitted vaginosis/vaginitis. AB - Although much has been learned about sexually transmissible forms of vaginitis/vaginosis during the past decade, therapeutic options for these disorders remain limited. A single 2-g oral dose of metronidazole still remains highly effective against most Trichomonas vaginalis infections. Mildly resistant infections can usually be cured with metronidazole oral doses of 2 g daily for 3 7 days. When highly resistant infections occur, toxic levels of metronidazole may be needed for the drug to cure the infection. Metronidazole (500 mg twice daily for 7 days) continues to be highly efficacious in the treatment of bacterial vaginosis. Shorter oral treatment regimens that use single 2-g doses of metronidazole for 2-3 days appear promising but may be associated with higher relapse rates. Oral clindamycin (300 mg twice daily) or local 2% clindamycin cream (once daily for 7 days) also may be effective. Metronidazole intravaginal sponges (250-1,000 mg) used for 3 days may also be effective in the treatment of bacterial vaginosis. PMID- 2201079 TI - Sexual assault and sexually transmitted diseases: detection and management in adults and children. AB - Sexual assault is a frequently occurring violent crime. Sexually transmitted diseases (STDs) may be acquired during assault. Reported rates of gonorrhea and syphilis in adult victims range from 6% to 12% and from 0% to 3%, respectively. The risk of acquiring other STDs cannot be quantified, although the risk of infection with Chlamydia trachomatis appears highest. In abused children, gonococcal and chlamydial infections are the most frequent findings. In both adults and children, postassault infections with viral agents of STDs, including herpes simplex viruses, hepatitis B virus, and human immunodeficiency virus, have been described. Sensitive, competent care for victims of sexual abuse includes evaluation for STDs soon after the assault and during follow-up. PMID- 2201080 TI - History of rhinology: nasal specula around the turn of the 19th-20th century. AB - This review is an excursion into the past to find the prototypes of the various nasal specula around the beginning of our century. The oldest prototype is documented in the ancient Hindu text Sushruta-samhita (6th century BC): a tubular nasal speculum. The bivalved forceps-like nasal speculum was mentioned by Hippocrates and can be followed with and without self-retaining mechanisms to the modifications of Killian and of Cottle. U- or Y-shaped springlike devices to open the nares have been known since the publication of Arnold de Villanova from the 13th century. They were reintroduced in a modification by Thudichum in 1868. Fraenkel's speculum (1872) combines fenestrated blades with a screw-set for self retaining. Duply (1868) modified the split and funnel-shaped ear speculum of Bonnafont, the branches of which can be varied by a screw. In addition to this description of the prototypes of specula a short development of the facilities to illuminate the inner nose is given starting with the sun light and ending with the glass fiberoptic. PMID- 2201081 TI - Hemangiopericytoma of the nasal cavity. AB - Hemangiopericytomas are unusual vascular tumours that rarely occur in the paranasal sinuses and nasal cavity. They are thought to arise from pericytes that surround capillaries, however, there is no proven etiology of these tumours. The diagnosis cannot be made based on gross morphologic characteristics nor on frozen section biopsy. Instead, the diagnosis is dependent on careful histologic examination and reticulum staining. The diagnosis can be confirmed by electron microscopy. The histologic picture is greatly varied from tumour to tumour and within a given tumour itself. The clinical course of hemangiopericytomas ranges from benign to malignant with possible distant metastases and cannot be reliably predicted by histologic criteria. Hemangiopericytomas of the nose and paranasal sinuses are thought to behave less aggressively than those occurring in other parts of the body. Lymph node metastasis is rare and elective neck dissection is not indicated. The accepted treatment of these tumours is wide surgical excision, however adequate surgical margins are usually difficult in the sinonasal region. As a result, hemangiopericytomas can exhibit a high recurrence rate. Therefore, it is mandatory that these patients be followed carefully for the remainder of their lives. PMID- 2201082 TI - Combatting anxiety. PMID- 2201083 TI - Drug test value by transcranial Doppler in the diagnosis of neurologic vascular diseases. AB - The response to various drugs was studied in relation to intracranial vascularization under ultrasound control. The investigation was made in 461 patients (258 females and 203 males) aged between 18 and 87 years. Vasoactive substances interacting with the synaptic neurotransmitters metabolism directly or via CNS were used: papaverine, vincamine, sadamin, nicergoline, carbocromen, clonidine, captopril, magnesium sulphate, nifedipine, piracetam, nicotine, caffeine, dipyridamole, histamine, fentanyl. The normal arterial response was compared with the response of the involved atherosclerotic artery or with congenital malformation. The tests value in the diagnosis of neurologic vascular diseases is discussed. PMID- 2201084 TI - Cancer prevention and control. PMID- 2201085 TI - Cancer prevention through physician intervention. PMID- 2201086 TI - Toward a tobacco-free society. PMID- 2201087 TI - The importance and nature of cancer prevention trials. PMID- 2201088 TI - Research priorities in large bowel cancer prevention. PMID- 2201089 TI - Screening and early cancer detection. AB - NCI is the primary research institution that has funded most of the research to establish evidence of benefit from mass cancer screening. A study of prostate, lung, and colorectal cancer is presently being planned. These trials are large, expensive, and require 10 to 15 years or longer to complete. RCST trials are only feasible in the three or four most common sites. While developing better evidence, NCI suggests the Working Guidelines for the Early Detection of Cancer in seven sites where direct and/or indirect evidence suggests benefit. The potential for early cancer detection to contribute to a decrease in cancer mortality is great. However, unless early detection is applied by the public and by physicians, it is useless. It is hoped that this chapter has been helpful to physicians and oncologists in judging these matters and applying the benefits to patients. PMID- 2201090 TI - Worksite health promotion for cancer control. PMID- 2201091 TI - Diffusion and adoption of state-of-the-art therapy. PMID- 2201092 TI - Achieving a public health impact from cancer-control research. PMID- 2201093 TI - The future of cancer prevention and control. PMID- 2201094 TI - Compression ultrasonography as a reliable imaging monitor in deep venous thrombosis. AB - Our experience at Hippokration Athens Hospital with high-resolution real-time ultrasonography of the deep veins of the lower extremities is described, drawn from the results of a prospective comparative study of 65 patients. We used a combination of sonography and contrast venography for the detection of deep venous thrombosis (DVT). Of the study group, 33 had clinically suspected DVT, 20 were asymptomatic high-risk patients, while 12 with varicosities of the leg and scheduled for saphenectomy were examined preoperatively for deep venous patency confirmation. For all patients, venography, the reference method, was performed within 12 hours of the ultrasound scan. Since 29 of the examinations were bilateral, the total number of extremities studied was 94. The sonographic criteria analyzed were the intraluminal echogenicity and the venous compressibility with the ultrasound transducer probe. In addition, the response of the common femoral vein to the Valsalva maneuver was studied. Among these three criteria, compressibility was by far the most accurate. Noncompressible abnormal veins were noted in all of the 24 extremities with proximal thrombosis and in six of the 12 with thrombosis limited to the calf veins. Thus, the sensitivity of the compressibility criterion was 100 per cent for proximal and 50 per cent for isolated calf venous thrombosis (83 per cent). All venographically patent veins were fully compressible (specificity, 100 per cent). Abnormal intraluminal echoes were found in 18 of the 36 extremities with thrombosis but not in those with negative findings on venography. Sensitivity of intraluminal echogenicity was, therefore, 50 per cent and specificity, 100 per cent. For the Valsalva criterion, the standard lower normal limit of 10 per cent was applied, leading to 40 per cent sensitivity and 93 per cent specificity rates. In comparison with venography, ultrasonography underestimated the extent of thrombosis in 60 per cent of the true-positive examinations, although never to a clinically significant degree. In conclusion, compression ultrasonography, a technique based upon the unique criterion of venous compressibility, is a highly accurate and objective noninvasive diagnostic method, and is also suitable as a screening test. We urge clinicians to support their therapeutic decisions concerning the management of DVT with it. PMID- 2201095 TI - Douglas Waddell Jolly as a pioneer in the surgical treatment of trauma. PMID- 2201096 TI - Flow cytometry and prognostic implications in patients with solid tumors. AB - Flow cytometric DNA content analysis is a rapid, quantitative method of determining the DNA ploidy status and proliferative index of a given tumor. Abnormal DNA content, or aneuploidy, has been recognized as a marker of malignancy and is present in about 70 per cent of solid tumors. In the majority of solid tumors, the consensus is that the presence of an aneuploid tumor predicts a poorer over-all survival rate and a shorter disease-free interval, indicating that patients with diploid tumors have a more favorable prognosis than those with aneuploid tumors. The prognostic implications of an abnormal DNA content, therefore, suggest either a higher risk of relapse, a worsening of survival rate or a risk for progression of disease in stages I and II carcinoma of the breast, carcinoma of the colon and rectum, superficial carcinoma of the bladder and malignant melanoma. Thus, the assessment of cellular DNA content should be regarded as an additional prognostic determinant and should play an ancillary role in the decisions regarding the management of patients with malignant disease. With the introduction of more sophisticated technology, it will be possible to simultaneously assay for DNA ploidy and cell cycle distribution in addition to a series of tumor markers, such as CEA, and various products of oncogenes, thus providing further understanding of the heterogeneity of solid tumor cells. PMID- 2201097 TI - Surveillance strategies after resection of carcinoma of the colon and rectum. AB - The primary aim of postoperative surveillance of patients with carcinoma of the colon and rectum is to detect recurrent tumor when cure is still possible. Most recurrences are detected within 30 months after the initial operation. Patients who have had carcinoma of the colon and rectum must be observed not only because of the risk of recurrence or metastatic disease but also because of the increased risk of subsequent primary carcinomas of the colon and rectum as well as of other sites. Careful history-taking and thorough physical examination provide the first indication of tumor recurrence in as many as 48 per cent of instances. Although the liver is the most common site of metastases from carcinoma of the colon, liver chemistry tests are seldom the first to indicate recurrent disease. Fecal occult blood testing, roentgenography with barium enema and colonoscopy are useful surveillance tools, not for detecting recurrences but for detecting second primary carcinomas. Imaging techniques, such as intravenous pyelography, CT and scintigraphy of liver and spleen are generally not cost-effective in surveillance, but MRI and ultrasonography have shown some promise in detection of recurrence without exposing patients to ionizing radiation. The most effective indicator of recurrent disease is a progressive increase in serial levels of CEA. When CEA levels rise and other methods of imaging cannot account for the change, second-look operation is generally appropriate. PMID- 2201098 TI - Spinal extradural angiolipoma: a report of two cases and review of the literature. AB - Extradural angiolipomas are rare tumors that can produce spinal cord compression. Two patients with thoracic spinal angiolipoma are presented that were treated with surgical resection and radiation. The histological and clinical features of the 18 previously reported cases of these tumors are discussed. PMID- 2201099 TI - Computed tomography-guided and stereotactic techniques in the diagnosis and treatment of cerebral tuberculoma. AB - The advantages of computed tomography-guided preoperative localization of brain lesions are illustrated in four cases of solitary tuberculoma and in one case of tuberculous abscess of both the cerebrum and the cerebellum. The role of stereotactic diagnostic techniques is emphasized. The clinical presentation and the computed tomography findings in these patients were equivalent to those from glial or metastatic tumors. Synchronous pulmonary tuberculosis was not present in these patients, but in three patients there was metachronous tuberculosis. Tuberculous meningitis had not developed in any of the patients. PMID- 2201100 TI - Victor Horsley, John Marshall, nerve stretching, and the nervi nervorum. AB - In his early professional life, Victor Horsley was registrar and assistant to Mr. John Marshall, anatomist, surgeon, and president of the Royal College of Surgeons. In helping with the research for the Bradshaw Lecture on Nerve Stretching given by Marshall in 1883, Horsley demonstrated changes in nerve fibers due to mechanical stretching of the sciatic nerve, and he also demonstrated small nerve fibers in the sheaths of peripheral nerves--the so called nervi nervorum. Marshall attributed the benefits of nerve stretching in sciatica to the interference with these nervi nervorum hitherto considered to exist only in the sheath of the optic nerve. PMID- 2201101 TI - No signs of increased thrombin generation in menopause. PMID- 2201102 TI - Warfarin has no negative impact on fibrinolysis. PMID- 2201103 TI - Benign migratory stomatitis: a literature review and case report. AB - Although benign migratory stomatitis (BMS) was first reported in the literature as early as 1955 (Cooke), fewer than 40 cases have been recorded. This article reviews the literature and describes a case of BMS involving the ventral surface of the tongue of a 74-year-old male. This is the first South African case to be reported. PMID- 2201104 TI - Regulation of testicular function by insulin and transforming growth factor-beta. AB - Hyperinsulinism is associated with disorders of androgen production in humans. We have studied the effects of insulin and insulin-like growth factor-1 on androgen production in vitro using a crude preparation of mouse Leydig cells incubated with luteinizing hormone in a serum-free medium. We found a positive correlation between testosterone production and the luteinizing hormone dose over 3 hours. Exposure of the cells for 1 hour to insulin (1 micrograms/ml) prior to the addition of luteinizing hormone significantly augmented the amount of testosterone produced in response to the gonadotropin when added after this preincubation. In contrast, prior exposure of the cells to proinsulin (30 micrograms/ml), insulin-like growth factor-1 (30 ng/ml), or epidermal growth factor-1 (1 micrograms/ml) did not influence the testosterone response to luteinizing hormone. Transforming growth factor-beta reduced the testosterone response to luteinizing hormone. Transforming growth factor-beta (1,000 pg/ml) blocked the insulin augmentation of luteinizing hormone-stimulated testosterone production. We conclude that insulin has an endocrine effect on testosterone production by mouse Leydig cells in vitro. Furthermore, the Leydig cell response to insulin is itself sensitive to interaction with transforming growth factor beta which may operate as part of the paracrine control of Leydig cell function. PMID- 2201106 TI - Jail suicide and legal redress. AB - Suicide is the leading cause of death in jails. Especially at risk are pretrial detainees. This paper provides clinicians who serve as consultants to jails with an overview of legal precedent concerning liability for jail suicide on the federal appellate, federal district, and state levels. Liability on the federal level is based upon actions involving deliberate indifference or gross negligence. A table is provided granting a summary view of appellate-level decisions on liability for jail suicide. Liability on the state level involves lesser standards of negligence. The paper concludes with several liability generating scenarios. PMID- 2201107 TI - Opportunistic infections in AIDS in developed and developing countries. AB - The acquired immune deficiency syndrome (AIDS) is fundamentally the same disease in all parts of the world, but the prevalence of microorganisms in an environment governs the patterns of disease arising from reactivated latent infections, invading pathogens and opportunistic infections. AIDS in Africa has certain characteristic presentations. Enteropathic AIDS is most common: Cryptosporidium and Isospora belli are identified in up to 60% of patients, but it is uncertain whether they are the causes of diarrhoea. Pneumocystis carinii pneumonia is rare. Tuberculosis, both pulmonary and extrapulmonary, is the supreme complicating infection. Herpes zoster is frequently the first clinical presentation, and has a 95% positive predictive value for HIV positivity. Measles may be more frequent in infants born to HIV-infected mothers, and appears to be worse in HIV-infected children. There is accelerated progress of both diseases in patients infected by HIV and Mycobacterium leprae. Salmonellosis is frequent. There is no direct interaction between malaria and HIV, but, by being a potent cause of anaemia, malaria enhances transmission of HIV to children through blood transfusion. HIV positive subjects are liable to new or reactivated visceral leishmaniasis with dissemination to unusual sites. Cerebral toxoplasmosis is common. There are no apparent interactions between HIV and helminths, although there is one report of hyperinfection with Strongyloides stercoralis. Cryptococcal meningitis has high frequency. Infections with Histoplasma encapsulatum are common in tropical America, but there has been no increase of frequency of H. duboisii in Africa since the advent of AIDS. PMID- 2201105 TI - In vivo plaque-forming cell suppression by methyl 20 beta-dihydroprednisolonate. AB - Methyl 20 beta-dihydroprednisolonate, a new local antiinflammatory steroid, and its ester hydrolysis product, 20 beta-dihydroprednisolonic acid, were evaluated for potential immunosuppressive actions as determined by the splenic plaque forming cell response assay. The parent compound, prednisolone, was used as a comparative agent. All three corticosteroid agents, when administered intraperitoneally or subcutaneously by separate injections given at the same time as antigen, demonstrated significant dose-related suppression of this immunologic parameter. In a croton oil-induced inflammation test (ear challenge in mice), methyl 20 beta-dihydroprednisolonate demonstrated significant antiinflammatory effects, but only in the ear to which it was applied. The comparative drug, prednisolone, significantly reduced inflammation in the ear to which it was applied and in the contralateral ear as well. The methyl ester derivative demonstrated effective antiinflammatory activity when applied topically in the oxazolone delayed-type hypersensitivity test (ear challenge in mice). The results seen in the plaque-forming cell response are in contrast to the generally noted lack of systemic glucocorticoid actions of the steroid acid ester derivatives reported in other studies. PMID- 2201108 TI - Septicaemia in patients with AIDS. AB - During a 5 year period at St Stephen's hospital, London, septicaemia was detected in 66 patients with the acquired immune deficiency syndrome (AIDS) and in 13 other patients with non-AIDS-associated HIV infections. The most frequent pathogens in patients with AIDS were Mycobacterium avium-intracellulare, Streptococcus pneumoniae, Pseudomonas aeruginosa, Cryptococcus neoformans and staphylococci. A series of HIV-associated septicaemias reported from other centres in different countries has shown great variation in the pattern of aetiological agents observed, which may partly reflect differences in the local socio-economic condition, ethnic backgrounds, other predisposing factors, and blood culture techniques. Salmonella species were a prominent cause of septicaemia in several reports. Most centres have also reported an increasing problem with septicaemias associated with intravenous lines in patients receiving antiviral or other parenteral drug therapy. PMID- 2201109 TI - Protozoan infections. AB - Protozoan infections, against which immunity is predominantly T cell mediated, are likely to be more severe in patients with the acquired immune deficiency syndrome (AIDS) than in immunocompetent hosts. Leishmaniasis, toxoplasmosis and cryptosporidiosis are examples, the last two being particularly common in AIDS patients. Cerebral toxoplasmosis almost always results from recrudescence of latent infections acquired earlier in life. Depletion of T-helper (CD4+) lymphocytes enables bradyzoites to survive if released from cysts in the brain of patients. In the absence of immune pressure bradyzoites revert to tachyzoites and multiply to cause a rapidly developing, necrotizing encephalitis which needs immediate treatment. AIDS patients, especially those who are negative for antibodies to Toxoplasma, should avoid cats, the source of oocysts, and undercooked meat which may contain tissue cysts, as primary infections may become systemic. Cryptosporidium infections are more likely to be primary infections. Sources of infection are other people, farm animals and pets and there is a significant risk from contaminated domestic water supplies. As infections cause a life-threatening secretory diarrhoea in AIDS patients, for which there is not satisfactory treatment at present, such patients should take steps to minimize the risk of infection. PMID- 2201110 TI - Problems of chemotherapy in multiply-infected AIDS patients. AB - Potential multiple opportunistic infections in patients with the acquired immune deficiency syndrome (AIDS) cause the clinician considerable problems. Firstly there is the problem of the correct diagnosis of which organism is producing symptoms and there is the possibility of more than one organism being responsible. Secondly when multiple drug therapy is used in AIDS patients it is likely to result in a number of adverse effects. These may be expected as part of the toxic profile of the drug but also may result from unexpected interactions, or exacerbations of underlying problems in individuals infected with human immunodeficiency virus. PMID- 2201111 TI - Missing infections in AIDS. AB - In north America and Europe, the opportunistic infections from which patients with acquired immune deficiency syndrome (AIDS) frequently suffer are Pneumocystis carinii pneumonia and Mycobacterium avium-intracellulare: in central Africa these infections are uncommon or non-existent. Serious infections with Entamoeba histolytica and Strongyloides stercoralis would be expected to occur in AIDS patients: they do not. Falciparum malaria might be expected to interact with HIV infection: it does not. The epidemiology and pathophysiology of these infections are discussed with respect to HIV co-infection. PMID- 2201112 TI - Virus infections in patients with AIDS. AB - Virus infections are common in patients with acquired immune deficiency syndrome (AIDS). Viruses can have two distinct relationships with human immunodeficiency virus (HIV); they can be opportunists if the second virus takes advantage of decreased immune function in the host or they can act as co-factors to accelerate the rate at which AIDS develops. Viruses acting as opportunists may cause no symptoms or may be life-threatening. Several, including herpes simplex, varicella zoster, cytomegalovirus and Epstein-Barr virus, can be treated with antiviral agents. Before concluding that a virus can act as a co-factor for HIV, several other possible relationships must be excluded including opportunism, co parameters of lifestyle and prognostic markers. Studies in vitro may suggest which viruses are potential co-factors but clear evidence can come only from carefully defined cohorts of patients. Recent evidence showing that cytomegalovirus can meet these criteria is presented. PMID- 2201113 TI - Impact of human immunodeficiency virus on transmission and severity of tuberculosis. AB - It is now clear that tuberculosis is one of the major diseases associated with human immunodeficiency virus (HIV) infection and the acquired immune deficiency syndrome both in developing countries and in disadvantaged groups in the northern hemisphere. In the USA, and probably several other countries, the annual incidence of tuberculosis is rising as a result of the HIV epidemic. This is probably a result of an increase in both pulmonary and, especially, extrapulmonary tuberculosis, due to reactivation of latent infections, but a secondary increase in the infection rate is also possible. The hard-won gains in tuberculosis control of the last 30 years are thus in jeopardy. This article focuses on the effect HIV is likely to have on the known risk factors for infection with Mycobacterium tuberculosis and for reactivation. Whilst HIV associated tuberculosis may be indistinguishable from HIV-negative disease, it is likely in other cases to present diagnostic difficulties, to respond poorly to treatment with more adverse effects, and to result in high early mortality, although this may not be due directly to tuberculosis. HIV-associated tuberculosis thus represents a major challenge to physicians, especially in developing countries, but like other forms of tuberculosis it is (i) treatable and (ii) preventable. PMID- 2201114 TI - [Nuclear medicine in neurology]. PMID- 2201115 TI - [Therapeutic roles of nuclear medicine]. PMID- 2201116 TI - Congenital urethral-perineal fistula: diagnosis and new surgical management. AB - Congenital posterior urethral-perineal fistula is a rare anomaly of which there have been only 6 reported cases to date. This report outlines the clinical presentation of another case and a unique surgical approach to its management, as well as a review of the English literature. PMID- 2201117 TI - Transrectal sonography for serial evaluation of prostatic malignancy. AB - Serial changes in the prostatic bed as identified by transrectal sonography in 31 patients with prostatic carcinoma were correlated with systemic change in disease. Seventy-three sonograms were performed, allowing interval change to be evaluated in 42 instances. Sonography demonstrating regression correlated with clinical response in 89 percent (8/9) of studies and with disease progression in 91 percent (10/11). Stable disease was correctly evaluated by sonography in only 56 percent (10/18) of studies. Six of those 8 incorrectly identified as stable were in men with prostatic irradiation prior to inclusion in this study. If they are excluded, stability was accurately gauged in 83 percent (10/12). Stability of the prostate on serial sonography may not accurately reflect clinical status in men with prior prostatic irradiation. In 1 patient abscess was superimposed on and could not be differentiated from tumor. Nodules of increased, decreased, and mixed echogenicity showed the same response to treatment as the total prostate volume. PMID- 2201118 TI - Synchronous, primary bilateral lymphoma of testes. AB - Lymphoma of the testicle is the most common testicular neoplasm in men over sixty years of age, but usually represents a secondary manifestation of systemic disease. This case report describes the rare phenomenon of a synchronous, primary bilateral lymphoma of the testes (Stage Ie) occurring in a sixty-eight-year-old man. PMID- 2201119 TI - Reducing rectal injury from sonographically-guided transrectal needle biopsy of prostate. The "rule of finger". PMID- 2201120 TI - Point of view: deja vu--again: advantages and limitations of methods for assessing penile arterial flow. PMID- 2201121 TI - [Formalization of the process of differential diagnosis of nevi and initial choroid melanomas with the aid of a diagnostic table]. AB - Basing on the results of a multidimensional discriminant computer-aided analysis of clinical findings in 11 patients with nevi and 102 with initial choroidal Stages TIa-TIb melanomas, the authors suggest formalization of the process of differential diagnosis between nevi and initial choroidal melanomas. For this purpose a diagnostic table with the minimal number of signs was developed. The disease can be diagnosed (the share of erroneous diagnoses is under 6 percent) with the use of just common instruments that can be found in any ophthalmology room. PMID- 2201122 TI - [Optometric services abroad (review of the literature)]. PMID- 2201123 TI - [Eye manifestations in myasthenia (review of the literature)]. PMID- 2201124 TI - [Memorable ophthalmological dates in 1990]. PMID- 2201125 TI - Sympathico-adrenal effects of endotoxaemia in cattle. AB - Intradermal injection of 46 micrograms E coli endotoxin had no effect on the plasma cortisol and noradrenaline concentrations of four dairy cows. Mean values were similar to normal values reported in the literature. Intravenous injection of 75 micrograms of endotoxin on the following day caused a massive increase in plasma cortisol concentrations which lasted for seven hours. Plasma noradrenaline concentrations increased rapidly after the intravenous administration of endotoxin and remained high for at least one hour. A possible relationship between endotoxaemia and the pathogenesis of acute laminitis is discussed. PMID- 2201126 TI - Otitis externa in a foxhound pack associated with Candida albicans. PMID- 2201127 TI - Bovine spongiform encephalopathy/scrapie. PMID- 2201128 TI - [The history of balneology. I. D. Iakhnin (on the centenary of his birth)]. PMID- 2201130 TI - [The treatment of acute heart failure]. AB - Acute cardiac failure is a symptom of a defined heart disease. Therapeutic efforts will only be successful, if the casual disease can be recognized. The clinical picture of cardiac failure is composed of a lot of pathophysiological and pathobiochemical developments. Some of them are still today completely or partly unknown. Each pharmacological intervention influences these regulations and reacts in every situation not only in the desirable but also in an unexpected way. Since we do not know the speed and direction of the developing cardiac failure, patients in NYHA II-III have to be sent to hospital. Starting the efficient treatment in time success can be expected without expensive diagnostics and monitoring techniques. But in some cases highly specialized equipment will be necessary and must be available. PMID- 2201129 TI - [The participation of the skin in realizing the action of therapeutic physical factors]. PMID- 2201131 TI - [The therapy of chronic heart failure]. AB - A rational therapy of the chronic cardiac insufficiency should be performed according to a certain scheme, in which case the knowledge of the basic disease is necessary for the causal treatment. Apart from the general measures the medicamentous therapy is of particular significance. Hereby up to now the digitalis glycosides remained the remedy of primary choice. They are without doubt indicated in the latent and manifest cardiac insufficiency, consequently from the transition of the NYHA stage II into stage III, in tachycardiac disturbances of rhythm also without cardiac insufficiency in form of auricular fibrillation and auricular flutter as well as in the paroxysmal supraventricular tachycardia. Prophylactic, preoperative applications of glycosides and such ones which are performed only for reasons of age are not justified. Also a maintenance therapy is in most cases no more necessary after removal of the cause of the cardiac insufficiency. - Diuretics are to be used in an insufficiency which continues existing despite application of glycosides. Their application must be performed as protracted as possible. - The therapies with vasodilators, such as prazosin, hydralazine and nitrates, which were performed during the last years, showed, indeed, initial success, but no long-term effect. Another fact it is, however, with the angiotensin-converting enzyme (ACE) inhibitors captopril and enalapril, which are to be regarded as second grade medicaments in combination with glycosides and diuretics. Whether or not they will supersede the glycosides, is at present still an open question. Other positively inotropic medicaments which in comparison to the glycosides show a larger therapeutic breadth are still being developed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2201132 TI - [The extension of heart failure therapy with vasodilators]. AB - By the introduction of the vasodilators into the therapy of the cardiac insufficiency particularly by the application of angiotensin-converting-enzyme (ACE) inhibitors advance could be obtained with regard the peripheral resistance which is always made evident as a sequel of the vasoconstriction in severe cardiac insufficiency the application of vasodilating substances (venous or arterial) leads to a relief of the heart with increase of the cardiac output, decrease of the congestion symptoms and partly amelioration of the exercise tolerance. Whereas all vasodilating substances show these effects in the acute experiment, in the long-term application due to the tolerance development no significant haemodynamic and clinical amelioration is to be made evident any more, with the exception of the ACE-inhibitors. Only the combination of nitrates and hydralazine showed favourable results with regard to the survival time. The therapy with ACE-inhibitors is, when they is used in an expert way and aimed, the hitherto most conducive one to success which has only slight side-effects. Because of the present knowledge all patients with a cardiac insufficiency of the degrees of severity III and IV, perhaps already beginning with degree of severity II, should, in addition to glycosides and diuretics, be treatment with ACE inhibitors, so far as no contraindication or intolerability are present. Otherwise an experiment with nitrates plus hydralazine is justified. PMID- 2201133 TI - [Drug therapy following heart valve prosthesis]. AB - Patients with prostheses of the cardiac valve are, related to the total population, only a small part. But their number permanently increases. Alone in our clinic since 1973 3,250 patients have been provided with artificial cardiac valves. Thus more and more physicians are confronted with the problems of these patients. The long-term results after replacement of the cardiac valves are very essentially influenced by the prevention and well-timed recognition of complications, respectively. For this reason the medicamentous therapy is demonstrated on the basis of own experiences and modern literature. It is clearly pointed out that after replacement of the cardiac valve a permanent cardiologic control is necessary. In detail is reported on the therapy of cardiac insufficiency including disturbances of the cardiac rhythm, on the prophylaxis of thromboembolism as well as on the prophylaxis of endocarditis. PMID- 2201134 TI - Frog virus 3-mediated translational shut-off: frog virus 3 messages are translationally more efficient than host and heterologous viral messages under conditions of increased translational stress. AB - Frog virus 3 rapidly and selectively blocks host cell translation while synthesizing more than 60 virus-specific polypeptides. Previous work indicated that virus infection led to activation of a kinase that phosphorylated and, as a consequence, inactivated eIF-2. Although phosphorylation of eIF-2 could explain the rapid decline in host cell translation, it could not explain how viral protein synthesis persisted in the face of host shut-off. To explain this phenomenon, we speculated that viral messages, either as a consequence of their higher translational efficiency or their greater abundance, were able to outcompete host messages for the remaining translational initiation complexes. To test this hypothesis, the relative translational efficiency of three characteristic FV3 messages was measured against that of several model messages. Translational efficiency was determined by monitoring the resistance (and hence the competitiveness) of a given transcript to increasing concentrations of salt in vitro and in vivo. In both rabbit reticulocyte lysates and wheat germ extracts, FV3 messages were more resistant to supra-optimal concentrations of potassium acetate than globin message and three BMV transcripts. In vivo, FV3 polypeptides were synthesized in the presence of salt concentrations that blocked host cell protein synthesis. These results suggest that the selective translation of FV3 messages in virus-infected cells may partly be due to the higher translational efficiency of viral messages. Structural features that contribute to translational efficiency are discussed. PMID- 2201135 TI - [Indications and technic of external fixation in acute management of polytrauma]. AB - The application of external fixation in the multiple injured patient permits rapid stabilisation of fractures and excellent preservation of soft tissue without an additional systemic load after traumatic shock. Acute fixation in the primary care is achieved by particular constructions for the pelvis and femur and modifications of standard-techniques for the tibia and joint-transfixation. In most cases secondary completions or alterations in the method of treatment are necessary. PMID- 2201136 TI - [Fractures of the head of the tibia. Evaluation of an East German multicenter study 1981-1985]. AB - The successful therapy of fractures of caput tibiae has always been the "haut ecol" of every treatment of fractures. A study made by 52 surgical clinics of the GDR which examined 1,954 patients who were under medical therapy between 1981 to 1985 summarizes the results. The patients have been examined for a period of 4.5 years in average. The study comparing the results of conservative and surgical medical therapy shows that there is no difference between the results of both methods of medical therapy regardless whether all kinds of fractures or whether only the same kinds of fractures were compared. Even if we consider the impression-fractures we come to the same result although we were of the opinion up to now, that impression-fractures should be treated in a surgical way only. The results of the study make clear the necessity of a strong indication for a surgical treatment and also that an early functional conservative therapy has the same results. PMID- 2201137 TI - [Osteoporosis as a cause of pathological fractures]. AB - More than a fifth of all females suffer from the risk to develop spinal osteoporosis. Hip fractures occur about 50,000 times per year in Federative Republic of Germany, about 1/3 in males and 2/3 in females. Estrogen deficiency is a risk factor of major importance for females; both sexes gain risk because of nutritional calcium deficiency and reduced mobility. Estrogen replacement therapy was proven to reduce the risk in females; and calcium supply reduces risk in both sexes. Therapy of developed spinal osteoporosis includes fluorides, calcium, vitamin D and calcitonin. No drug therapy has been developed so far for patients with senile osteoporosis and hip fractures. PMID- 2201138 TI - [Strategy in endoprosthesis infections]. AB - Infection in total hip replacement, its definition, normal history and treatment are reviewed. A case with a two stage revision with the use of a cementless resection prosthesis is presented. PMID- 2201139 TI - [Surgical treatment of peripheral nerve injuries. Evaluation of a multicenter study]. AB - In a retrospective study 674 nerve injuries of the upper limb were analysed, which were treated by operative management in 10 hospitals of the GDR. The median nerve (226 cases) and the ulnar nerve (209 cases) most were frequently concerned. 427 injured nerves were reconstructed primary or early secondary. In 46.3% epineural nerve suture was performed and in 23% interfascicular nerve grafting. Good or very good results occurred in 71% (motor recovery) and 70.7% (sensory recovery) according to the scheme of Highet. The best results occurred after primary reconstruction independent of operative technique. The results get worse with increasing age. PMID- 2201140 TI - [Surgical heritage. Memories and reflections of Egbert Schwarz 1890-1966)]. PMID- 2201141 TI - [Surgical risk in old age. Prospective evaluation of a prognosis index]. AB - A prognostic index of octogenarians was calculated by a critical retrospective analysis of our results of the outcome after operations. In the years 1986-1988 this index was prospective validated at 381 patients over 80 years old. The accuracy was 85%. The other quality parameter (sensitivity, specificity, negative and positive predictive values) of the decision point of our prognostic model reached good or very good values too. This results showed the possibility of application for the recommended prognostic index. In the last three years the postoperative mortality has fallen essential in general surgery. At present the mortality estimate 20% for emergency and elective operations for the whole hospital stay of the patients. The direct clinical utility of risk analyses to work out prognostically statements was proved by this study. PMID- 2201142 TI - [Atraumatic rupture of the esophagus (Boerhaave syndrome)]. AB - The complete atraumatic rupture of an intact esophageal wall had been described first by Boerhaave in 1724. We reviewed 424 published cases from that time until 1985 regarding the clinical feature and different types of diagnosis and treatment. An over all mortality rate between 28 and 85% was found which is highly influenced by the time the right diagnosis is made and by the choice of treatment. It is demonstrated that only an early diagnosis followed by immediate surgery (suture of the perforation protected by a pleural flap) can improve the poor prognosis of this illness. PMID- 2201143 TI - [Reconstructive pancreas surgery in chronic pancreatitis]. AB - An account is given in this paper of possibilities for reconstructive procedures, primarily in the wake of partial pancreatectomy, with reference being made to experience obtained by the author form surgical treatment of chronic pancreatitis. Benefits and setbacks of various methods are discussed in some detail, for example, duodenum or stomach preservation. The author continues to support cephalic duodenopancreatectomy with pancreaticogastrostomy on patients with chronic pancreatitis, however, with due observance of stringent criteria. That approach is considered equal to drainage methods. PMID- 2201144 TI - [Splenopexy of a floating spleen]. PMID- 2201146 TI - [The F. M. Blumental' Institute--its public and scientific activities (from the history of Soviet microbiology)]. PMID- 2201145 TI - [Nonsaccharolytic dark-pigmented Bacteroides in human pathology]. PMID- 2201147 TI - [The physicochemical and biochemical characteristics of the cell walls in M+ and M- variants of Streptococcus group A type 29]. AB - The amino acid composition of cell walls and surface proteins, isolated from virulent (M+) and avirulent (M-) streptococcal strains (group A, type 29) has been determined by the method of E. H. Beachey et al. The kinetics of the lysis and proteolysis of streptococcal cell walls with muramidase and protease obtained from Actinomyces levoris and streptolysin has been studied. The constants describing the progress rates of these processes has been determined; their values in case of both lysis and proteolysis are higher in virulent strains than in avirulent ones. PMID- 2201148 TI - [The formulation of epidemiological hypotheses by using the methods of multivariate statistical analysis]. AB - The work demonstrates the main approaches to the use of the methods of multidimensional analysis for the creation of a hypothesis on the mechanism of the epidemiological process of dysentery in organized groups. The main risk factors have been established, and their role in the formation of annual, all-the year-round and seasonal dysentery morbidity has been quantitatively evaluated. The results of analysis show the existence of diverse variants of the alimentary route of the transmission of infection, maintaining the epidemic process of dysentery, and the necessity of differentiating measures for the prophylaxis of all-the-year-round and seasonal morbidity. PMID- 2201149 TI - [HBs antigenemia in glomerulonephritis in children]. AB - Altogether 194 glomerulonephritis patients were examined by three methods: countercurrent immunoelectrophoresis, passive hemagglutination test, and enzyme immunoassay. Use of the most sensitive method, viz. enzyme immunoassay, has yielded the highest HBsAg detection rate: 29.1% in acute glomerulonephritis and 21.4% in chronic glomerulonephritis. This method may be recommended for the examination of glomerulonephritis patients whose sera contain HBsAg in low titers. PMID- 2201150 TI - [The pathogenicity factors of the opportunistic bacteria that cause diarrhea]. PMID- 2201151 TI - [Modern views on the pathogenesis of dysentery: the role of invasion and the toxic action of Shigella]. PMID- 2201152 TI - [A receptor for the Fc fragment of human IgG in the causative agent of tularemia]. AB - In 4 Francisella tularensis strains varying in virulence a receptor to Fc site of human IgG has been detected. This receptor consists of two active components with molecular weights of 67,000 and 40,000, competing for binding on Fc site of human IgG with Staphylococcus aureus protein A. PMID- 2201153 TI - [The effect of the cationic proteins of human blood cells on the growth of Escherichia coli]. AB - The antibacterial effect of cationic proteins (CP) on donor leukocytes and thrombocytes with respect to the growth of E. coli has been demonstrated in vitro, the maximum recorded inhibition being caused by the action of leukocytic CP. Differences in the inhibitory action may be linked with the presence of anomalies in the amino acid composition of leukocytic CP and thrombocytic CP, manifested by the deterioration of the basic properties of the latter, as well as by the fractional composition whose characteristic features for thrombocytic CP are the appearance of high-molecular components and a decrease in the proportion of low-molecular fractions. In patients with different forms of leukosis (chronic myeloleukemia, chronic lympholeukemia, acute myelomonoblastic leukosis) leukocytic CP retain their antibacterial activity. Under the action of blood cell CP changes in the outer and cytoplasmic membranes have been noted. PMID- 2201154 TI - [The reactogenicity and immunological efficacy of a Klebsiella vaccine in donors]. AB - Klebsiella vaccine, when injected subcutaneously to donors, proved to be faintly reactogenic and safe. The injection of the vaccine had no effect on changes in the morphological composition of peripheral blood and on liver function. In persons with the initially low content of IgG an increase in this characteristic was observed after immunization. No changes in the synthesis of IgE occurred in healthy donors under the influence of immunization. The vaccine was shown to be immunogenic when introduced according to immunization schedules comprising 3 and 5 injections, the titer of Klebsiella antibodies increasing 3- to 5-fold. PMID- 2201155 TI - [The danger of hepatitis B virus infection from transfusions of plasma in which the HBs-antigen was detected retrospectively by highly sensitive methods]. AB - The prospective dynamic laboratory and clinical study of premature children was carried out: 55 children who received plasma transfusion during the first weeks of their life and were retrospectively (i. e. after plasma transfusion) found to have HBsAg detected by the passive hemagglutination (PHA) test, the enzyme immunoassay (EIA) and the radioimmunoassay (RIA) and 127 children who received the transfusion of plasma found to be HBsAg-negative according to the results of EIA and RIA. As revealed in this study, the risk of hepatitis B virus infection in such children after the transfusion of plasma containing HBsAg at low concentrations, determined only in the PHA test or in EIA and RIA, was, respectively, 7.5 and 6.3 times greater than in children receiving plasma found to be HBsAg-negative according to the results of EIA and RIA. The results of this investigation showed the tendency towards a decrease not only in the total contamination of plasma recipients with hepatitis B virus, but also in morbidity rate in icteric forms of acute posttransfusion hepatitis B, depending on the concentration of HBsAg in plasma used for transfusion. PMID- 2201156 TI - [The use of commercial immunoenzyme kits for the diagnosis of toxoplasmosis]. AB - The results of comparative study of sera obtained from donors and from several groups of patients with suspected toxoplasmosis are presented. The study has been carried out with the use of commercial enzyme immunoassay (EIA) kits: Toxoplasma gondii IgG EIA and Toxoplasma gondii IgM EIA manufactured by Labsystems (Finland), Sevatest ELISA IgG Toxo Micro I manufactured by Sevac (Czechoslovakia). Statistical processing of the results has confirmed the identity of these kits. The necessity of using evaluation criteria (the separation point, the scale for the interpretation of results) when working with the Sevac kits is emphasized. Comparative evaluation of antibody profiles in the sera under test suggests that the titer less than 1:1600 should be regarded as the separation point for these kits. IgM antibodies to T. gondii have been found only in 22% of patients with high titers of IgG antibodies. PMID- 2201157 TI - [Changes in the activity of the natural killers under the influence of genetically engineered alpha 2-interferon in patients with viral hepatitis B]. AB - The functional activity of natural killer cells (NKC) in 90 patients with acute viral hepatitis B was studied. As a result, the importance of this characteristic as a criterion of effectiveness of alpha 2-interferon obtained by gene engineering techniques was shown. The study revealed the presence of inverse relationship between the level of the functional activity of NKC and the severity of acute viral hepatitis B at the peak of the disease. The character of the influence of alpha 2-interferon on the cytotoxicity of NKC depended on the time of the use of the preparation. Administration of reaferon till day 7 of jaundice promoted a significant increase of the initially low activity of NKC in comparison with that in patients receiving common therapy. This was accompanied by rapid changes of the clinical signs of the disease and accelerated elimination of the virus from the blood. When the preparation was administered after day 6 of jaundice the activity of NKC increased slowly and only at the period of convalescence. These results recommend measurements of NKC activity as a criterion for the evaluation of the effectiveness of alpha 2-interferon. PMID- 2201158 TI - [Biochemical and molecular biological studies on beta-glucuronidase in myelogenous leukemic cells]. AB - beta-Glucuronidase purified from normal human tissues (placenta, liver and spleen) and granulocytes was composed of 80 kilo-Dalton (kDa), 64 kDa and 18 kDa subunits. The enzyme from human myelogenous leukemic cells contained a 80 kDa subunit as a major component. Amino acid sequencing revealed that N-terminal regions of the 80 kDa from CML cells and the 18 kDa from placenta were identical, and the sequence of the 64 kDa from placenta was identical to the downstream sequence of Gly138 in the 80 kDa enzyme. Therefore, it is probable that the 80 kDa is a precursor form and the 64 kDa is a mature form that is derived by removal of N-terminal 18 kDa peptide (137 amino acids) from the precursor form. These observation simply that proteolytic processing of this enzyme is impaired in myelogenous leukemic cells. The possibility of impaired protease activity against the 80 kDa subunit in CML cells was excluded, since the 80 kDa was not susceptible to several protease sources from normal tissues (placenta and liver) and granulocytes under a variety of reaction conditions. In addition no mutation of the primary structure in myelogenous leukemic cells was detected through analysis of DNA encoding for a peptide, including Gly138 of the enzyme. Therefore, it is suggested that abnormal processing of beta-GUase in the myelogenous leukemic cells is due to alteration in transcriptional or translational step. PMID- 2201159 TI - Acta sixty years ago. Evaluation of radical treatment of abortion peritonitis. PMID- 2201160 TI - Bacteriological characterization of the effusion material in an animal model for serous and purulent otitis media. AB - By means of cleaving the soft palate and blocking the Eustachian tube, two otomicroscopically well defined types of otitis media, serous and purulent, were created in an animal model (rat). The microbiological pattern of these conditions were characterized at 1, 2, 3, 4 and 6 weeks after the onset. Samples were collected from the middle ear cavity via the bulla tympanica and cultured for aerobic as well as anaerobic bacteria. The serous effusion was culture-negative. The purulent effusion material was culture positive, and mixed with Gram-positive (S. aureus, S. epidermidis, Strept. faecalis) and Gram-negative (E. coli, Proteus mirabilis) bacteria of which the latter dominated. No anaerobic species were detected. The study shows that the two otomicroscopically different types of otitis media also differ with regard to the microbiological pattern. The rat thus provides the opportunity to study these two different inflammatory middle ear responses--infectious and noninfectious--during standardized conditions. PMID- 2201161 TI - An alternative treatment for the reduction of tympanic membrane perforations: sodium hyaluronate. A double blind study. AB - Topical treatment with 1% sterile sodium hyaluronate solution applied on the tympanic perforation membrane has been suggested as an alternative to surgical treatment in one study only. To further investigate the effects of such a treatment, we designed a double blind study comparing topical administration of 1% sodium hyaluronate with that of 2% methylcellulose solution (placebo). After treatment the degree of perforation healing was evaluated and expressed in percentage of reduction area. The reduced area turned out to be significantly different in the group treated with sodium hyaluronate solution as compared to the placebo group. We believe that sodium hyaluronate is an alternative to myringoplasty for selected tympanic membrane perforations. PMID- 2201163 TI - Treatment of sinus empyema in adults. A coordinated Nordic multicenter trial of cefixime vs. cefaclor. AB - In sinus empyema, H. influenzae is the most prevalent pathogen in some subpopulations and in case of therapeutic failure. Cefixime, the first oral cephalosporin of the 3rd generation, is highly potent in vitro against H. influenzae. To study the efficacy and safety of cefixime in adults with acute sinusitis, a coordinated, double-blind multicenter trial was designed for purulent cases, as confirmed by antral aspiration. A total of 364 patients were enrolled in the study with 125 cases randomized to the reference group, assigned to treatment with cefaclor. Evaluation was based on clinical outcome and on antral reaspiration (86% of the cases). No significant differences between the treatment groups were found, as regards short-term or long-term clinical outcome. However, the clinical examination overestimated the therapeutic results. Only 4% of the patients were considered as failures, but the re-aspiration demonstrated remaining suppuration in 14% of all cases (p less than 0.001). Based on re aspiration, the failure rate among patients with initial growth of pathogens was lower for cefixime (8%) than for cefaclor (20%) (p less than 0.05). Such a difference was not found among patients with growth of H. influenzae. No serious adverse reactions were recorded, but loose stools and diarrhoea were significantly more frequent in the cefixime treatment group. Five patients (2%) in the cefixime treatment group discontinued their treatment due to adverse events. PMID- 2201162 TI - Topical terlipressin (Glypressin) gel reduces nasal mucosal blood flow but leaves ongoing nose-bleeding unaffected. AB - Nasal bleeding where the lesion cannot clearly be localized is today usually treated with different forms of nasal packings which are traumatizing to the nasal mucosa and often causes the patient discomfort. In an attempt to develop a more convenient form of treatment the effect of two vasoconstrictor gels on nasal mucosal blood flow was evaluated. Terlipressin gel was shown to reduce nasal blood flow in a dose-dependent way. Therefore, this gel was chosen in a double blind comparison with placebo in the treatment of 44 patients with posterior epistaxis. Although 50% of the patients did stop bleeding after topical gel administration into the nose there was no statistically significant difference in effect between those who received terlipressin gel and those who received placebo gel. We cannot disregard the fact, however, that the gel in itself has a beneficial effect on nose-bleeding. PMID- 2201164 TI - The link between infant mortality and birth rates--the importance of breastfeeding as a common factor. PMID- 2201165 TI - Glycine, glycyl-glycine and maltodextrin based oral rehydration solution. Assessment of efficacy and safety in comparison to standard ORS. AB - We evaluated the efficacy and safety of an oral rehydration solution containing glycyl-glycine, glycine, and maltodextrin (GGG-ORS), in comparison to the glucose based ORS (standard ORS). The osmolality of the GGG-ORS (305 mOsm/l) and standard ORS (311 mOsm/l) was similar. Ninety-two children presenting with acute gastroenteritis and moderate dehydration, aged 3 months to 3 years, were randomly assigned to receive standard ORS or GGG-ORS. All the patients were successfully rehydrated orally. The two groups were comparable for baseline characteristics including the microbial etiology. Rotavirus (49%, 36%), ETEC (11%, 18%) or a combination of rotavirus and ETEC (15%, 9%) were the main stool pathogens isolated. There was no significant difference in the mean stool output or duration of diarrhoea between the two groups. Patients in the GGG-ORS group had higher urine output (p less than 0.01) and weight gain (p less than 0.05) in the initial 6 hours when feeding was withheld, but no such differences were observed beyond this period. Hypernatremia did not develop in any patient during the study. We conclude that glycine and glycyl-glycine supplemented oral rehydration solution does not have any therapeutic advantage in the treatment of acute gastroenteritis with moderate dehydration caused predominantly by rotavirus. PMID- 2201166 TI - Early treatment of idiopathic respiratory distress syndrome using binasal continuous positive airway pressure. AB - During a 3-year period (1979-81) 85 premature infants with idiopathic respiratory distress (IRDS) were treated early with an easily applicable light-weight CPAP system with a binasal tube and a gas jet. We used conservative criteria for ventilator treatment. The treatment proved sufficient in 18 out of 25 infants with a birth weight less than or equal to 1500 g and in 53 out of 60 infants with a birth weight greater than 1500 g. Seven infants developed pneumothorax during CPAP treatment. Seventy-four infants survived, all without bronchopulmonary dysplasia. At the age of 1.5-4.5 years the incidence of respiratory tract infections did not differ from that in a group of siblings; and the incidence of lower respiratory tract infections was low compared to previous studies. With the criteria used, early CPAP proved effective in the majority of infants with IRDS. PMID- 2201167 TI - Sensory-motor and cognitive functioning in children who have undergone bone marrow transplantation. AB - Sensory-motor and cognitive functioning was investigated in a group of 32 children treated with bone marrow transplantation (BMT), 1-6 years after treatment. Twenty-five of the patients had suffered from leukemia. The BMT procedure had involved a regimen of cytostatic drugs and, for leukemia patients, total body irradiation at a dose of 10 Gy, administered in one session. Cytostatic drugs and irradiation are known to be potentially neurotoxic, particularly when combined. The examination involved four neuropsychological tests of sensory-motor and cognitive functioning, as well as an age-appropriate intelligence test. For control the bone marrow donors (n = 32), siblings of the patients, were also investigated. A pronounced delay in motor development was found in four children, who had been treated with BMT including total body irradiation before 3 years of age. Patients between 3 and 11 years of age at BMT were at a slight disadvantage, compared to donors, on tasks involving perceptual and fine motor speed. In older patients no deficits were observed. PMID- 2201168 TI - Age-related changes in uptake and release on L-[3H]noradrenaline in brain slices of senescence accelerated mouse. AB - High K+ and N-methyl-D-aspartate (NMDA) evoked L-[3H]noradrenaline (NA) release to a similar degree in the brain slices of 1-month-old senescence-accelerated resistant mice (SAM-R/1) and senescence-accelerated prone mice (SAM-P/8). However, 30 mM KCl-induced L-[3H]NA release significantly diminished in SAM-P/8 from 3 to 12 months without changing in SAM-R/1. In addition, NMDA-induced L [3H]NA release was also reduced at 3 months and lowered to a level of spontaneous release at 12 months in SAM-P/8, but no age-related changes in SAM-R/1 were observed. It is suggested that NA release from NA nerve terminals responsive to depolarization is reduced in SAM-P/8 at an earlier stage than in SAM-R/1. Furthermore, NMDA receptors which could be localized in the soma and/or nerve terminals, seem to be involved in NA release and to be decreased with advancing age in SAM-P/8. PMID- 2201169 TI - Expression of muscle-specific isozymes of phosphorylase and creatine kinase in human muscle fibers cultured aneurally in serum-free, hormonally/chemically enriched medium. AB - Primary cultures of muscle cells derived from a biopsied adult human skeletal muscle were grown up to 6 weeks in a hormonally/chemically enriched serum-free medium. The expression of muscle-specific isozymes of creatine kinase, glycogen phosphorylase, and phosphoglycerate mutase, indicative of muscle cell maturation, was studied after 1, 4 and 6 weeks of growth. The maturation of muscle fibers cultured in serum-free medium was comparable to that achieved by muscle fibers cultured in medium containing 10% serum and supplemented with growth factors (insulin, epidermal growth factor, and fibroblastic growth factor) and was greater than that achieved in medium containing 10% serum only. Our study demonstrates that adult human muscle can be cultured aneurally for a long period of time in a serum-free medium, and that it can achieve a high degree of maturation. This study provides an important basis for investigations related to: (1) assessment of the influence of individual components of the medium on human muscle maturation in culture; (2) studies of regulation of abnormal gene expression in diseased human muscle cultured in serum-fre medium. PMID- 2201172 TI - [Frontal sinus osteoma in a skull found in the archeological excavations at the old Louvre]. AB - A skeleton dating 8th-9th centuries exhumed from the Napoleon square at the Louvre, presents a voluminous ivory or benign osteomata at its frontal sinus. Anthropological and pathological studies give matter to introduce this osteomata on the morphological and demographic problematica ot the benign tumours. PMID- 2201170 TI - Retinoids increase perinatal spinal cord neuronal survival and astroglial differentiation. AB - In this report we demonstrate that retinol and retinoic acid (RA) increase the survival and morphological differentiation of rat spinal cord neurons in vitro. Micromolar amounts of retinol and RA increased the number of surviving neurons by 2- to 3-fold and affected neuritic density resulting in increased secondary and tertiary processes compared to untreated sister cultures. A marked morphological differentiation of the astrocyte population in conjunction with an antiproliferative effect in the presence of retinoids were apparent. These trophic effects occurred mainly after 5 days in vitro, a time that corresponds to the time of birth in vivo. Retinoic acid exerted a direct trophic effect on spinal cord neurons in the absence of glial cells while retinol lost its effectiveness. Metabolic labeling suggested that retinol is converted to the biologically active RA within astrocytes but not in neurons. Taken together, our results have demonstrated direct trophic effects of RA on spinal cord neurons and have suggested another role for astrocytes in the maintenance of normal neural physiology by regulating RA concentrations through the oxidation of retinol. PMID- 2201171 TI - Endothelin causes contraction of canine and bovine arterial smooth muscle in vitro and in vivo. AB - We have studied the effect of endothelin, an endothelium-derived peptide, on isolated canine and bovine cerebral arteries in vitro and on canine vertebral blood flow (VBF) in vivo. Endothelin produced a dose-dependent contraction of canine and bovine arterial smooth muscle with ED50 values ranging from 4 to 8 nM. The response to endothelin developed slowly and persisted as a sustained contraction. Maximal contraction by endothelin required the presence of extracellular calcium and was independent of the presence of endothelium. The maximal contraction produced by endothelin was approximately 2-3 times greater than that produced by neuropeptide Y or angiotensin II. The injection of endothelin into the vertebral artery decreased vertebral blood flow (VBF) dose dependently without affecting systemic blood pressure or heart rate. The decrease in VBF produced by endothelin was long-lasting, like that produced by neuropeptide Y, but more potent. The present data, together with our previous study demonstrating that the intracisternal injection of endothelin induces an unusually long-lasting decrease in the basilar artery diameter angiographically, suggests that endothelin may act as a long-lasting vasoconstrictor in cerebral vascular disease. PMID- 2201173 TI - [Solitary plasmocytoma of the mandible: study of a case]. AB - The isolated plasmocytoma of the maxilla is an extremely rare tumor. It is classified in the group of low-grade B lymphomas. Its clinical and even radiological diagnosis remains difficult. Some authors, such as H.S. LOH in 1983, have attempted to regroup all reported cases in the literature, but many are incomplete, especially those which were first published. Most of the time, it is the pathological examination that rectifies the diagnosis and, currently, the immuno-chemical examination that confirms this diagnosis; this was demonstrated in the case reported here. PMID- 2201174 TI - [The Armatron technic: a solution to control proprioceptive sense in a unit implant. An alternative to a bridge]. AB - The Armatron technique permits the easy construction of single-implants controlling the proprioceptive sensitivity with the use of a natural tooth. This is an elegant solution, rather mildly disabling, with simple concept and realization. Besides, it is a non aggressive and reasonable alternative to costly solutions such as bridges on intact teeth or implants. Although simple and safe, the Armatron technique was only made possible by the use of modern materials as well as surgical tools with high definition technology which guarantee the reliability of this method. PMID- 2201175 TI - [Descriptive review of lymphoid tumors of the jaws]. AB - This study reviews the various lymphoid tumors affecting the bony maxilla. If cervico-facial localizations of lymphoid tumors are frequent, they are relatively rare within the bony maxilla. Hodgkin's-like lymphomas are exceptionally rare: non-Hodgkin's lymphomas, among which are Burkitt's lymphomas and Ewing's sarcomas, are slightly more frequent. Granulocytic sarcomas, myelomas and plasmacytomas are rarely found in the maxilla. The different epidemiological, etiological, clinical, radiological, histological and therapeutic characteristics of each tumor is described along with a review of the recent literature. PMID- 2201177 TI - Vasodilators have not been shown to be of value in all patients with chronic congestive heart failure due to left ventricular systolic dysfunction. PMID- 2201176 TI - Recombinant interleukin-1 and tumor necrosis factor induce neutrophil migration "in vivo" by indirect mechanisms. AB - The alpha and beta forms of recombinant interleukin-1 (IL-1 alpha and IL-1 beta) and of recombinant Tumor Necrosis Factor (TNF alpha and TNF beta) induced dose dependent neutrophil migration into rat peritoneal cavities. Migration induced by both IL-1s showed a bell-shaped dose-response curve and IL-1 beta was 3-fold more potent than IL-1 alpha. Pretreatment of the animals with dexamethasone or depletion of the peritoneal macrophage population, abolished the neutrophil migration induced by the four cytokines. "In vitro" stimulation of macrophage monolayers with IL-1 beta and the TNFs released a factor into the supernatant which, unlike these cytokines, induced neutrophil migration in dexamethasone pretreated animals. These results suggest that the neutrophil migration induced by IL-1 alpha, IL-1 beta, TNF alpha and TNF beta is not due to a direct effect on neutrophils, but occurs via the release of a chemotactic factor(s) from resident macrophages. PMID- 2201178 TI - All patients with left ventricular systolic dysfunction should be treated with an angiotensin-converting enzyme inhibitor: a protagonist's viewpoint. PMID- 2201179 TI - Nitrates are effective in the treatment of chronic congestive heart failure: the protagonist's view. PMID- 2201180 TI - Should complex ventricular arrhythmias in patients with congestive heart failure be treated? A protagonist's viewpoint. PMID- 2201181 TI - Should asymptomatic ventricular arrhythmia in patients with congestive heart failure be treated? An antagonist's viewpoint. PMID- 2201182 TI - Are nitrates effective in the treatment of chronic heart failure? Antagonist's viewpoint. PMID- 2201183 TI - Future perspectives in the management of congestive heart failure. PMID- 2201184 TI - Future perspectives in basic science understanding of congestive heart failure. PMID- 2201185 TI - Autonomic nervous system activity during myocardial ischemia in man estimated by power spectral analysis of heart period variability. The Multicenter Study of Silent Myocardial Ischemia Investigators. PMID- 2201186 TI - Effects of the sulfonylureas on muscle glucose homeostasis. AB - The sulfonylureas have pharmacologic effects both on insulin secretion by pancreatic beta cells and on responsiveness to insulin in peripheral tissues. The effects of the sulfonylureas on skeletal muscle may have a particularly significant influence on glucose homeostasis because of the important role of muscle as a peripheral site of glucose clearance. Under most physiologic conditions, the rate-limiting step for glucose utilization in muscle is its uptake across the plasma membrane; for this reason, the effects of the sulfonylureas on glucose transport have been a focus for study. In muscle tissue, the sulfonylureas appear to augment the stimulation of glucose uptake by insulin but not to alter glucose homeostasis in the absence of insulin. The mechanism of this effect, which requires several hours of exposure to a sulfonylurea, has not been defined. Although studies with cultured muscle cells have yielded inconsistent findings, recent work with the L6 rat skeletal muscle cell line demonstrated that the sulfonylureas exerted effects similar to those in muscle tissue both in time course and in requirement for co-stimulation by insulin. Mechanistic studies in L6 cells have shown that the sulfonylureas induce increased glucose transporter messenger ribonucleic acid levels and increased total cellular content of transporter proteins even in the absence of insulin, but that insulin is required for augmented glucose uptake activity. Based on these data, it has been suggested that insulin may cause the activation of transporters synthesized in response to sulfonylureas. The definition of the mechanism of this synergistic response to insulin and the sulfonylureas in L6 muscle cells may give insight into the in vivo molecular events involved in the action of the sulfonylureas in skeletal muscle. PMID- 2201187 TI - Transvaginal ultrasonographic detection of congenital anomalies in the first trimester. AB - Transvaginal ultrasonography enables detailed visualization of the first trimester pregnancy. Thirty-three structural anomalies have been diagnosed in the first trimester of pregnancy during a 2-year study period. An understanding of normal embryonic development is essential before attempting diagnosis in this gestational period. PMID- 2201188 TI - Assessment of cerebral hemodynamics in pregnant women by internal carotid artery pulsed Doppler velocimetry. AB - To date, no studies have been done of serial changes in maternal cerebral hemodynamics during pregnancy. We used the noninvasive method of Doppler velocimetry to assess cerebral hemodynamics in pregnant women. Velocimetry measurements of the internal carotid artery were performed in 17 normal nonpregnant women and 77 women with uncomplicated pregnancies with a 4 MHz pulsed Doppler ultrasound system. Peak systolic and mean velocities in the first and second trimesters were almost the same as those in nonpregnant women, whereas they became slower in the third trimester. Pulsatility index from 4 to 31 weeks' gestation was significantly higher than in nonpregnant women, but fell to the nonpregnant value after 32 weeks. Doppler velocimetry was found to be an extremely useful method of cerebrohemodynamic evaluation in pregnant women. PMID- 2201189 TI - Bacterial vaginosis: diagnostic and pathogenetic findings during topical clindamycin therapy. AB - We examined subjective and objective correlates among 67 women with symptomatic bacterial vaginosis before and after treatment with intravaginal clindamycin or placebo. We found no preponderance of any sexual practices among these patients. Nine patients (13.4%) had had hysterectomy. Whereas odor and discharge were the most common symptoms, 30 patients (44.8%) also complained of vulvovaginal irritation. Symptoms correlated poorly with objective therapeutic outcome. On examination the diagnosis would have been missed in seven patients (10.4%) if the clinician relied on presence of an abnormal vaginal discharge to suggest bacterial vaginosis. Vaginal pH greater than 4.5 was found immediately after curative therapy in 59.6% of patients. Mobiluncus spp. morphotypes were 99.0% specific and 52.1% sensitive and proline aminopeptidase activity in vaginal fluid was 84.4% sensitive and 70.2% specific for diagnosis. Our Gram stain criteria yielded no false-negative results, 6.1% false-positive, and frequent indeterminate results after therapy. We found little evidence for sexual transmission of bacterial vaginosis. Recurrence after effective therapy was not predicted by vaginal pH elevation, positive or indeterminate Gram stain result, or positive proline aminopeptidase test. PMID- 2201190 TI - Induction of labor with mifepristone (RU 486) in intrauterine fetal death. AB - In a double-blind controlled multicentric study involving 94 patients with an intrauterine fetal death, we investigated the efficacy and tolerance of mifepristone (RU 486), a steroid compound that antagonizes progesterone action at the receptor level. Success of treatment was defined as the occurrence of fetal expulsion within 72 hours after the first drug intake. Mifepristone treatment (600 mg per day for 2 days) was considered to be effective in 29 of 46 patients (63%). There were only eight successes in 48 patients (17.4%) in the placebo group (p = 0.001, chi 2 test). Tolerance was good in the mifepristone group. In the placebo group, disseminated intravascular coagulation occurred in one woman for whom the investigator waited several weeks for spontaneous expulsion. This large double-blind controlled study provides evidence that mifepristone is of interest in the management of intrauterine fetal death. It could provide a pharmacologic alternative to the use of prostaglandins in this indication. PMID- 2201191 TI - Retropubic long-needle suspension procedures for stress urinary incontinence. AB - A brief review of the Pereyra and the Stamey procedures and their modifications, including success rates and potential problems, is presented. A new modified technique is described that has potential advantages of ease, rapidity, less dissection, and less blood loss than may be seen with the modified Pereyra procedure and less chance of foreign body reaction than may be seen with the Stamey procedure. Twenty patients with significant stress urinary incontinence (14 with concurrent severe pelvic relaxation) underwent the procedure with an 80% cure plus 5% significant improvement rate noted 12 to 39 months after operation. All failures occurred in patients who were obese and involved apparent suture pull-through. Complications were minimal. Suggested causes for failures are discussed. PMID- 2201192 TI - Ductus arteriosus flow velocity modulation by fetal breathing movements as a measure of fetal lung development. AB - A test is needed that would accurately predict favorable neonatal lung performance in the presence of prolonged severe oligohydramnios caused by ruptured membranes so that optimal obstetric care can be provided. We propose such a test that is based on the degree of modulation of fetal ductal blood flow velocity by fetal breathing movements after maternal glucose loading. In a prospective cross-sectional study of 49 normal pregnancies (50 fetuses) between 25 and 38 weeks an exponential increase in breathing-related ductal blood flow velocity modulation was observed with advancing gestational age, reflecting the developing pulmonary vascular bed. Fetal ductal flow velocity waveforms were also recorded in 13 cases of prolonged severe oligohydramnios after ruptured membranes before 28 weeks' gestation. Normal ductal blood flow velocity modulation values were associated with normal neonatal lung performance, whereas reduced ductal blood flow velocity modulation values were associated with pulmonary hypoplasia. Fetal breathing-related ductal flow velocity modulation appears to be a promising predictor of neonatal lung performance. PMID- 2201193 TI - Prenatal diagnosis of a chest wall mass with ultrasonography and Doppler velocimetry. A case report. AB - An isolated mass protruding from the chest wall of the fetus was visualized by ultrasonography. Doppler velocimetry over the mass revealed low-resistance blood flow through cystic areas, implicating a highly vascular lesion. An operative delivery was performed to avoid possible rupture of the mass. PMID- 2201194 TI - Twin-to-twin transfusion syndrome. PMID- 2201195 TI - Appropriate screening tests. PMID- 2201196 TI - Expression of the bcl-2 oncogene protein is not specific for the 14;18 chromosomal translocation. AB - It has been reported previously that the bcl-2 protooncogene protein is detectable in neoplastic cells from cases of human lymphoma in which the 14;18 chromosomal translocation is present, but not in lymphomas that lack this chromosomal rearrangement or in normal lymphoid tissue. In the present study we confirmed, by immunohistologic labeling with polyclonal and monoclonal antibodies, that bcl-2 protein is strongly expressed in many cases of follicular lymphoma and that these neoplastic follicles differ clearly from their nonmalignant counterpart (reactive germinal centres) in which bcl-2 protein is undetectable. However we also found bcl-2 protein in normal T- and B-lymphoid cells and in a variety of lymphoproliferative disorders in which the 14;18 translocation is not present. It is therefore concluded that expression of bcl-2 protein is not a specific marker for lymphomas bearing the 14;18 chromosomal translocation and that the observations of other investigators may have reflected the inadequate sensitivity of their staining procedure. PMID- 2201197 TI - Immunoreactive A4 and gamma-trace peptide colocalization in amyloidotic arteriolar lesions in brains of patients with Alzheimer's disease. AB - Cerebral amyloid angiopathy (CAA) defines a biochemically heterogeneous entity that manifests as effacement of cerebral microvessel walls by a fibrillar material with characteristic tinctorial properties. In biochemical terms, the amyloid that infiltrates blood vessels in CAA is composed of the A4 or beta peptide of Alzheimer's disease (AD), a molecule related to gamma trace or cystatin C (seen in patients with hereditary cerebral hemorrhage with amyloidosis in Iceland, HCHWA-I), or the PrP characteristic of spongiform encephalopathy and scrapie. Using antibodies to synthetic peptides representing portions of the 4.2 kd Alzheimer A4 peptide and the gamma-trace peptide, we immunostained sections of brain from patients with AD, senile dementia of Alzheimer's type, and CAA with associated leukoencephalopathy. Immunohistochemical studies demonstrated colocalization of the A4 and gamma-trace peptides within arteriolar walls, but only rarely in A4 amyloidotic capillaries or senile plaque cores of amyloid. When gamma-tracelike reactivity was noted in capillary walls, it was sometimes noted within the cytoplasm of pericytes. Immunostaining was always more intense when the anti-A4 antibody was used as the primary antibody. Gamma-trace immunostaining was more prominent on the adventitial component of arteriolar walls, whereas A4 staining was usually seen more diffusely throughout the blood vessel wall, especially in the media. Rarely individual pericytelike cells showed prominent gamma-trace immunoreactivity. These findings suggest that A4 and gamma-tracelike molecules may colocalize within arteriolar walls within the brains of patients with AD, and highlight the fact that CAA identified with AD and HCHWA-I are not as biochemically distinct as was assumed previously. Furthermore these findings suggest that other peptidases or protease inhibitors may be found within amyloidotic microvessel walls and may contribute to senile brain change and CAA related strokes, including hemorrhage and encephalomalacia. PMID- 2201198 TI - Inflammatory pseudotumor of lymph nodes. Immunohistochemical evidence for its fibrohistiocytic nature. AB - Five cases of inflammatory pseudotumor (IPT) of the lymph node were investigated by means of light microscopy and immunohistochemistry to elucidate its cellular composition. The IPT is composed of a proliferation of spindle cells, inflammatory cells, and small vessels, forming high and poor cellular areas. Many spindle cells correspond to activated histiocytes as they coexpress vimentin and macrophage-associated markers; they are intermingled with vimentin-positive fibroblasts and variable numbers of vimentin- and actin-positive myofibroblasts. This mixed-cell proliferation invades and/or destroys medium- and large-sized vessels in all cases. This study indicates that the spindle cell proliferation, identified as histiocytic and fibroblastic in nature, represents the main component of the nodal IPT. We speculate that release of cytokines by the activated histiocytes may result in the development of the complex histopathologic aspects of this inflammatory process and, if inappropriate, may represent the underlying pathogenic mechanism. PMID- 2201199 TI - Immunotherapy of collagen-induced arthritis by a T-cell antiproliferative molecule. AB - The present study describes a novel experimental immunotherapeutic methodology for the reduction of inflammatory synovitis that is noted in an animal model of rheumatoid arthritis. The reduction in inflammation is noted in the animals administered a contra-interleukin-2 (IL-2) cytokine secreted by a cloned T-cell line. The mechanism of reduction of inflammation by this cytokine is through the inhibition of activation and differentiation of T lymphocytes. The cytokine inhibits the in vitro mitogen activation of T-cell lymphocytes as well as antigen specific activation of a collagen type II specific T-cell line. In addition, decreased levels of messenger RNA coding for interleukin-2 are noted in T lymphocytes and IL-2 activation of the collagen type II specific cell line is inhibited by the contra-IL-2 cytokine. This initial description of a reduction in inflammation by a contra-IL-2 lymphokine suggests that immunoregulatory biologic molecules that are antagonists to IL-2 may be useful for the experimental immunotherapy of cartilage connective tissue pathology. PMID- 2201200 TI - Focal toxicity of oxysterols in vascular smooth muscle cell culture. A model of the atherosclerotic core region. AB - Cell necrosis and reactive cellular processes in and near the atherosclerotic core region might result from short-range interactions with toxic lipids. To model these interactions in cell culture, focal crystalline deposits of cholestane-3 beta,5 alpha,6 beta-triol, 25-OH cholesterol, and cholesterol were overlaid by a collagen gel, on which canine aortic smooth muscle cells were seeded. Oxysterols, but not cholesterol, caused focally decreased plating efficiency and cell death, leading to the formation of a persistent circular gap in the cell culture. Cholestanetriol was largely removed from the culture dishes over 3 to 4 weeks, whereas cholesterol and 25-OH cholesterol were largely retained. Smooth muscle cells were motile even in proximity to oxysterol crystals, with occasional suicidal migration toward the crystals. Chemoattraction, however, could not be demonstrated. Despite toxicity, cholestanetriol did not appear to alter the fraction of cells exhibiting 3H thymidine uptake, even in areas close to the crystals. Thus, oxysterols may be toxic to some cells, without causing major impairment of the migration and proliferation of nearby cells. This would allow the simultaneous occurrence of cell death and proliferation evident in atherosclerosis. PMID- 2201201 TI - Lipoprotein degradation and cholesterol esterification in primary cell cultures of rabbit atherosclerotic lesions. AB - Lipoprotein metabolism and cholesterol accumulation in atherosclerotic lesions was studied using enzymatically isolated primary cell cultures from aortas of rabbits made atherosclerotic by cholesterol feeding. The cultures consisted of macrophages and smooth muscle cells, thus resembling, in composition, fatty streak lesions. The mean (+/- SD) cholesteryl ester content of the dispersed cells was 1059 +/- 445 micrograms/mg cell protein, but it declined steeply during 1 week in primary culture. The uptake of low-density lipoprotein (LDL), beta migrating very low-density lipoprotein (beta-VLDL), and acetylated LDL (acetyl LDL), labeled with 125I or with the fluorescent probe 1,1'-dioctadecyl-3,3,3',3'- tetramethylindocarbocyanine (DiI), was studied in 2-day-old primary cultures. DiI acetyl-LDL was avidly taken up by the macrophages and, to a lesser extent, by some smooth muscle cells. The uptake of DiI-beta-VLDL by the macrophages was weaker and less homogeneous than that of DiI-acetyl-LDL. The degradation rates of 125I-labeled beta-VLDL, LDL and acetyl-LDL were 135 +/- 54, 195 +/- 20, and 697 +/- 14 ng/mg cell protein/8 hours, respectively. Incubation with unlabeled acetyl LDL enhanced the incorporation of [3H]oleate into cholesteryl esters and increased the cellular cholesteryl ester content. These results suggest that arterial macrophages and, to some extent, smooth muscle cells from cholesterol fed rabbits actively metabolize acetyl-LDL and are thus capable of accumulating cholesteryl esters by uptake of modified forms of LDL. PMID- 2201202 TI - Physiology and biochemistry of vitamin D-dependent calcium binding proteins. AB - The vitamin D-dependent calcium binding proteins (calbindins) are members of the troponin-C superfamily of proteins that occur in a number of calcium-transporting tissues such as the intestine, the distal tubule of the kidney, and the placenta. They are also present in other tissues such as the brain, peripheral nervous system, pancreas, parathyroid gland, and bone. In some tissues, such as the adult brain, the proteins occur in the absence of the vitamin. The proteins bind calcium in "EF" hand structures and are "calcium-sensitive" in that they undergo a conformational change on binding calcium. They appear to enhance transcellular calcium transport and are frequently present in tissues that contain the plasma membrane calcium pump. PMID- 2201203 TI - Renal microvascular effects of endothelin. AB - The effects of endothelin 1, 2, and 3 (ET-1, -2, -3) on lumen diameter of individual afferent and efferent arterioles dissected from rabbit kidney were examined. ET-1 produced concentration-dependent and long-lasting decreases in lumen diameter in both arterioles. The 50% maximum response (EC50) values were 1.4 +/- 0.41 and 0.9 +/- 0.65 nM for afferent and efferent arterioles, respectively. In afferent arterioles, ET-2 produced decreases in lumen diameter (EC50 = 3.3 +/- 1.75 nM) that were indistinguishable from ET-1. However, ET-3 was considerably less potent (EC50 = 21.9 +/- 6.0 nM, P less than 0.05) than ET-1 or ET-2. Similar results were obtained in the efferent arteriole in which the EC50 for ET-2 (0.25 +/- 0.1 nM) was similar to ET-1, but ET-3 was significantly less potent (EC50 = 2.6 +/- 0.4 nM, P less than 0.05). Nicardipine (0.01-1 microM) produced concentration-dependent shifts in the ET-1 concentration-response curve in afferent arterioles. Verapamil (1 microM) also caused a significant shift in the ET-1 response curve. The contractile response to ET-1 was significantly more sensitive to nicardipine than was the response to norepinephrine. In contrast, the response of efferent arterioles to ET-1 and norepinephrine was unaffected by nicardipine or verapamil. The results demonstrate that ETs are potent vasoconstrictors of both the pre- and postglomerular microvasculature and may play a role in the regulation of renal hemodynamics.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2201204 TI - Interaction of captopril and ibuprofen on glomerular and tubular function in humans. AB - Renal hemodynamics and tubular solute and water handling were evaluated in normal subjects during water diuresis, before and after the acute administration of captopril, ibuprofen, or the combination of both drugs. The glomerular filtration increased after captopril administration but did not change after ibuprofen alone or in combination with captopril. Renal plasma flow increased with captopril alone and captopril plus ibuprofen but did not change after ibuprofen alone. Urine volume and Na excretion increased with captopril and decreased after ibuprofen; coadministration of ibuprofen attenuated the tubular effects produced by captopril alone. FELi, fractional delivery of solute to the distal nephron, and FELi-FENa, fractional distal reabsorption of solute, both significantly increased after captopril and decreased after ibuprofen but did not change with the combined regimen. (FELi-FENa)/FELi, fractional reabsorption of distally delivered Na, significantly decreased after captopril and increased after ibuprofen but remained unchanged after captopril plus ibuprofen. Thus captopril and ibuprofen have opposing effects on tubular Na and water handling, which are attenuated by the addition of the other drug. This interaction may have clinical relevance in patients with heart failure or hypertension, in whom captopril is used to enhance Na and water diuresis. PMID- 2201205 TI - Efficacy of nifedipine to prevent systemic and renal vasoconstrictor effects of endothelin. AB - We investigated whether systemic and renal vasoconstriction induced by porcine endothelin (endothelin 1) is prevented by nifedipine in awake normotensive rats. Endothelin (0.07-1.4 nmol/kg iv) induced a long-lasting increase in mean blood pressure (MBP) and a decrease in renal blood flow (RBF). Maximal decrease in RBF was 25 +/- 7% (0.07 nmol/kg), 40 +/- 2 (0.35), 67 +/- 5 (0.70), and 74 +/- 8 (1.4). Hemodynamic parameters were back to base line within 35 +/- 5 min (0.07 nmol/kg), 43 +/- 6 (0.35), 60 +/- 4 (0.70), and 81 +/- 7 (1.4). Intravenous bolus injection of either angiotensin II (ANG II, 0.006-0.024 nmol/kg) or norepinephrine (0.40-1.60 nmol/kg) caused a dose-related short-lasting increase in MBP and a decrease in RBF. Endothelin was less potent than ANG II (1:3.42) and more potent than norepinephrine (1:0.015) as a renal vasoconstrictor. Nifedipine (1 mg/kg ip) was equally effective in preventing the increase in MBP caused by endothelin, norepinephrine, or ANG II. It exerted a weaker protection on the renal hemodynamic response to endothelin compared with the inhibition of the other two vasoconstrictors. Thus the regression line representing the relationship between endothelin-induced changes in MBP and RBF was steeper in rats given nifedipine (slope: vehicle, -1.33; nifedipine, -5.50; P less than 0.05). These studies suggest that nifedipine can partially prevent systemic and renal vasoconstriction caused by exogenously administered endothelin in awake normotensive rats. PMID- 2201207 TI - Can pulsed Doppler technique measure changes in aortic blood flow in conscious rats? AB - To determine whether the pulsed Doppler (PD) system could be used to measure cardiac output we compared estimates of changes in aortic flow obtained from PD or electromagnetic (EM) probes on the ascending aorta in separate groups of conscious Long-Evans and Brattleboro rats under a variety of conditions. EM probes showed significant increases and decreases in aortic blood flow after administration of nitroprusside or methoxamine, respectively, but 20-MHz PD probes connected to a PD mainframe with a pulse repetition frequency (PRF) of 62.5 kHz showed no systematic changes in Doppler shift, due to "aliasing" of the Doppler signal. Aortic blood flow was significantly increased with intravenous volume expansion or isoprenaline administration, but these changes were not reliably detected by PD probes operating in a system with a PRF of 62.5 kHz. Calculation of expected peak Doppler shift signals from the phasic EM flow signal showed that these exceeded the Nyquist limit (PRF/2, i.e., 31.25 kHz) for the commercially available pulsed Doppler system. However, a modified pulsed Doppler module capable of resolving aliases and operating at a PRF of 125 kHz produced reliable results for changes in thoracic aortic Doppler shift, in good agreement with the EM probe data. In addition, placement of a cuff around the thoracic aorta did not alter cardiac baroreflex sensitivity. PMID- 2201206 TI - Endothelin in experimental congestive heart failure in the anesthetized dog. AB - Studies were performed in anesthetized dogs to determine plasma endothelin (ET) concentrations in the presence and absence of experimental congestive heart failure (CHF) produced by rapid ventricular pacing for 8 days. These studies were also designed to determine the effect of exogenous low-dose ET upon integrated cardiorenal and endocrine function in the presence and absence of CHF. In these studies, plasma ET was significantly elevated in CHF (3.25 +/- 0.39 pg/ml) compared with normal (1.03 +/- 0.21 pg/ml) or sham-operated (1.08 +/- 0.27 pg/ml) groups. Compared with the control group, which was characterized by a significant cardiorenal vasoconstrictor response to low-dose ET, a significant attenuation of the vasoconstrictor and antinatriuretic actions of ET was observed in the CHF group. Despite these differential responses, exogenous ET suppressed plasma renin activity (PRA) and activated aldosterone in both control and CHF groups. Thus these studies demonstrate for the first time that experimental CHF is characterized by elevated plasma ET in association with an attenuated cardiorenal response to exogenous ET. In contrast, low-dose ET inhibited PRC and activated aldosterone in the presence and absence of experimental CHF. PMID- 2201208 TI - Relationship between diastolic shape (eccentricity) and passive elastic properties in canine left ventricle. AB - This study was designed to investigate the relationship between left ventricular (LV) eccentricity, volume, and passive elastic properties. Eight open-chest fentanyl-anesthetized dogs were instrumented with an LV micromanometer, a remote controlled mitral valve occluder, and two pairs of ultrasonic crystals to measure anterior-posterior and base-apex dimensions. We identified the presence of elastic recoil forces with negative LV diastolic pressure in nonfilling diastoles (end-systolic volume clamp). Using linear regression analysis we related midwall eccentricity to volume in nonfilling diastoles at the time of LVPmin and at end diastole, and in normal beats at end systole at LVPmin and at end-diastole. Intersection of the end-systolic and end-diastolic lines (transitional volume, Vt = 38.0 + 6.4 ml) divides cycles with and without the presence of elastic recoil forces. Vt is analogous to the equilibrium volume (V0), determined as the volume intercept of the logarithmic passive pressure-volume (P-V) relationship using LV volume estimated from LV weights (V0 nl = 37.6 + 4.4 ml), or the volume intercept of the linearized P-V relationship calculated from a prolate spheroidal model using measured minor and major diameters (V0 l = 44.5 + 3.5 ml). Linear regression analysis was also used to relate the square of peak mitral flow (MF2) with the corresponding atrioventricular pressure gradient (delta P); the slope represents a dissipative constant for the cycles without, P = 0.00058(MF)2 + 0.35 (n = 48, r = 0.73), and with elastic recoil P = 0.00035(MF)2 + 0.21 (n = 24, r = 0.81).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2201209 TI - Left ventricular dysfunction in early E. coli endotoxemia: effects of naloxone. AB - Although the opiate receptor antagonist naloxone (NAL) has been reported to improve in vivo systolic performance of the heart in different circulatory shock syndromes, the influence of this drug on intrinsic cardiac mechanical function during hypodynamic circulatory states is unknown. The present study was designed to determine the effects of in vivo NAL on contraction-relaxation properties of isovolumic left ventricular (LV) preparations isolated from guinea pigs 4 h after induction of gram-negative endotoxemia. Animals were given a 1 mg/kg ip injection of Escherichia coli endotoxin and immediately treated intravenously with either NAL (4 mg/kg iv bolus plus 4 mg.kg-1.h-1 infusion) or an equivalent volume of saline. Endotoxin produced significant reduction of LV contractile function in coronary-perfused hearts, a response unaffected by NAL therapy. For example, LV systolic pressure at approximately 10 mmHg end-diastolic pressure averaged 78 +/- 3 and 82 +/- 6 mmHg in hearts from saline and NAL control animals, respectively, but only 41 +/- 2 and 40 +/- 2 mmHg in endotoxin and endotoxin plus NAL groups, respectively. LV end-diastolic pressure-volume relationships in endotoxin hearts were shifted upward and to the left of controls in the direction of decreased diastolic compliance (P less than 0.05). Importantly, in vivo NAL prevented the endotoxin-induced decrease in LV compliance of the isolated heart preparations (P less than 0.05). Thus intrinsic cardiac complications of early (4 h) nonhypotensive endotoxemia included decreased diastolic compliance as well as diminished contractility of the left ventricle. Only the diastolic compliance changes were NAL responsive and therefore may involve endogenous opioid systems in their pathophysiological expression. PMID- 2201210 TI - Modulation of transmembrane potential of isolated cardiac myocytes by insulin and isoproterenol. AB - Isolated muscle cells from adult rat heart have been used to study the effects of insulin and catecholamines on transmembrane potential by following triphenylmethylphosphonium cation uptake. Insulin was found to hyperpolarize the cells with a maximal effect of 3.2 +/- 0.7 mV (n = 4) at an insulin concentration of 3 x 10(-9) mol/l. This insulin action was fully antagonized by isoproterenol (10(-5) mol/l), which depolarized the cardiocytes in a dose-dependent fashion with a maximal effect of 9.5 +/- 2.2 mV. Treatment of cardiocytes with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid or CsCl resulted in a total loss of insulin action, whereas isoproterenol action was not affected. Cardiac myocytes from streptozotocin diabetic rats exhibited an unaltered hyperpolarization by insulin within the physiological concentration range. Isoproterenol now induced a biphasic response with a significant hyperpolarization at low doses and a decreased depolarization at maximal concentrations. In conclusion, 1) hormonal modulation of cardiac myocyte membrane potentials involves hyperpolarization by insulin and depolarization by beta agonists, 2) insulin action appears to be related to an increased potassium conductance and may be antagonized by beta-stimulation, and 3) membrane potential modulation may be profoundly altered in the diabetic state. PMID- 2201211 TI - Fetal blood volume restoration following rapid fetal hemorrhage. AB - In a previous study, we found that ovine fetal blood volume returned to normal in 3 h after a slow hemorrhage of 31% over 2 h; volume was slightly elevated at 24 25 h. In the present study, we explored the time required for blood volume restoration in late gestation fetal sheep following a rapid hemorrhage over 10 min. The rate of hemorrhage was constant within each fetus but varied among fetuses from 13.5 to 32.2%. Two fetuses that were hemorrhaged 32% of their initial blood volume over 10 min underwent cardiovascular collapse during the hemorrhage. In 10 fetuses that were hemorrhaged 21.0 +/- 1.7% (SE) over 10 min, 6.5 h were required for blood volume to return to control. Fetal arterial pressure, venous pressure, and heart rate decreased during and immediately after the hemorrhage and returned to normal within 1 h. Plasma arginine vasopressin (AVP) concentration and plasma renin activity (PRA) underwent large increases following the rapid hemorrhage. Volume restoration at 5-7 h posthemorrhage correlated negatively with PRA and norepinephrine (NE) concentration immediately after the hemorrhage. Three of the 10 fetuses died overnight, and in the remaining seven fetuses blood volume was 8.8 +/- 3.3% below control (P less than 0.01) at 24-25 h posthemorrhage. The fetuses were also hypoxic, acidotic, and had greatly elevated plasma AVP and NE concentrations at this time. We conclude that ovine fetuses are less able to survive a rapid hemorrhage compared with a slow hemorrhage of the same extent. In addition, fetal blood volume restoration is delayed after rapid hemorrhage, and the impaired restoration is to the detriment of the fetus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2201212 TI - Effects of temperature on nervous system: implications for behavioral performance. AB - Temperature change has a major impact on the function of the nervous system and its components, including altering synaptic gain and changing synaptic and conduction delays. Although many animals are subject to changes in body temperature, the degree of temperature change actually experienced by many poikilotherms is not well documented. The fact that many animals continue to exhibit coordinated sensorimotor function during changes in body temperature indicates that some form of temperature compensation has occurred within the nervous system. Compensations may occur automatically (opposing effects of temperature offsetting each other), they may be an inherent property of closed loop systems, or they may be effected by more sophisticated control mechanisms such as those of the vertebrate cerebellum. PMID- 2201213 TI - Influence of temperature on mechanics and energetics of muscle contraction. AB - Results gleaned from use of temperature as a probe to study skeletal muscle performance and mechanisms of activation and contraction are reviewed. Steady state and non-steady-state responses to changes in temperature are considered. Temperature sensitivities, Q10 values, of mechanical and energetic parameters range from nearly 1 to greater than 5 in frog skeletal muscle. Factors that are less temperature sensitive (Q10 less than or equal to 1.5) are peak tetanic force, instantaneous stiffness, curvature of force-velocity relation, magnitude of labile heat, and mechanical efficiency. Rates with intermediate temperature sensitivities (Q10 greater than 2 but less than 3) include rate of isometric force development, maximum shortening velocity, and relaxation from a brief tetanus. Rates with high temperature sensitivities (Q10 greater than 3) include cross-bridge turnover during an isometric tetanus, isometric economy, maximum power output, Ca2+ sequestration by sarcoplasmic reticulum, relaxation from a prolonged tetanus, and recovery metabolism. The observation that the Q10 for relaxation rate depends on tetanic duration can be explained in terms of the possible role of parvalbumin as a soluble relaxing factor. PMID- 2201214 TI - Effects of temperature and concomitant change in pH on muscle. AB - Contractile performance decreases with a decrease in temperature and increases with an increase in pH. In general, a decrease in ambient temperature is associated with an increase of the pH of the intracellular and extracellular fluids of ectotherms. Thus the concomitant increase in pH will to some extent counteract the effect of the decrease in temperature. We review the magnitude of this effect and show that it is modest for force (24%) but is small or negligible for speed or for variables involving time. Experiments with skinned fibers yield similar results to those with intact fibers. We argue that one important effect of the concomitant increase in pH is that it causes an increase in calcium sensitivity and that there may be a considerable metabolic saving associated with releasing less calcium at lower temperatures. PMID- 2201215 TI - Influence of temperature on muscle recruitment and muscle function in vivo. AB - Temperature has a large influence on the maximum velocity of shortening (Vmax) and maximum power output of muscle (Q10 = 1.5-3). In some animals, maximum performance and maximum sustainable performance show large temperature sensitivities, because these parameters are dependent solely on mechanical power output of the muscles. The mechanics of locomotion (sarcomere length excursions and muscle-shortening velocities, V) at a given speed, however, are precisely the same at all temperatures. Animals compensate for the diminished power output of their muscles at low temperatures by compressing their recruitment order into a narrower range of locomotor speeds, that is, recruiting more muscle fibers and faster fiber types at a given speed. By examining V/Vmax, I calculate that fish at 10 degrees C must recruit 1.53-fold greater fiber cross section than at 20 degrees C. V/Vmax also appears to be an important design constraint in muscle. It sets the lowest V and the highest V over which a muscle can be used effectively. Because the Vmax of carp slow red muscle has a Q10 of 1.6 between 10 and 20 degrees C, the slow aerobic fibers can be used over a 1.6-fold greater range of swim speeds at the warmer temperature. In some species of fish, Vmax can be increased during thermal acclimation, enabling animals to swim at higher speeds. PMID- 2201216 TI - Deactivation rate and shortening velocity as determinants of contractile frequency. AB - The kinetic properties of muscle that could influence locomotor frequency include rate of activation, rate of cross-bridge "attachment", intrinsic shortening velocity, and rate of deactivation. The latter two mechanisms are examined using examples from high-speed running in lizards and escape swimming in scallops. During running, inertial loading and elastic energy storage probably mitigate the effects of thermal alterations in intrinsic muscle shortening velocity. The result is a rather low thermal dependence of stride frequency over a 15-20 degree C temperature range. However, at lower temperatures, the longer times required for deactivation cause the thermal dependence of frequency to increase greatly. Scallops use a single muscle to swim by jet propulsion. In vivo shortening velocity in these animals also shows a low thermal dependence. As with high-speed running, the mechanics of jet propulsion may limit the effects of thermally induced changes in intrinsic shortening velocity. The largest thermal effect during swimming is on the initial phase of valve opening. The effects of temperature on the rate of deactivation of the adductor muscle could play an important role in limiting reextension of the muscle, which is dependent on elastic energy storage in the hinge ligament. These examples illustrate that the relative importance of various intrinsic contractile properties in controlling locomotor performance depends on the mechanics of the movements. PMID- 2201217 TI - Functional significance of metabolic responses to thermal acclimation in fish muscle. AB - Compensatory increases of the aerobic capacity of fish swimming muscle are frequently observed in response to cold acclimation. Such thermal compensation occurs both in fish that remain active in the cold and in fish that become dormant at cold temperatures. For cold-active fish, positive thermal compensation is best explained by conservation of the capacity for aerobic metabolic flux at low temperatures. The compensatory responses of cold-active species can be used to suggest the temperature range over which the activities of glycolytic and tricarboxylic acid cycle enzymes in a muscle, i.e., the muscle's "metabolic profile," can suffice. Analysis of the available data suggests that a 16 degrees C range of temperatures cannot be covered by one metabolic profile, even when the preferred temperatures are centered between the acclimation temperatures. For cold-inactive species that remain normoxic during winter dormancy, the compensatory metabolic modifications may facilitate lipid catabolism. Alternately, an increased aerobic capacity may be adaptive during the relatively cold periods that precede and follow winter dormancy. For goldfish and carp that encounter hypoxia and anoxia during winter dormancy, increased mitochondrial abundance could facilitate ethanol production during anoxia and the diffusion of oxygen to mitochondria during hypoxia. Finally, metabolic modifications during natural acclimatization indicate both thermal compensation and direct thermal effects and suggest that thermal compensation may be masked by reproductive and feeding activities. PMID- 2201218 TI - Thermal dependence of locomotor capacity. AB - The thermal dependence of locomotor performance capacity, particularly speed and endurance, in vertebrate ectotherms is examined. Most studies have found an optimal speed for performance at relatively high body temperatures, close to upper lethal limits. These performance capacities decrease markedly at low body temperatures and may be compensated by increments in aggressive or evasive behaviors. Relative ranking of performance is maintained among individuals across body temperatures. Acclimation of performance capacities is generally incomplete or entirely absent: most animals compensate locomotor performance rather poorly to cold exposure. Locomotor performance in different groups has been shown to possess the attributes (e.g., variability, repeatability, heritability, and differential survivorship) necessary for evolutionary adaptation, but interpretation of comparative data is complicated by phylogenetic differences among species studied. Controlled studies show partial but incomplete adaptation to environmental temperature. PMID- 2201219 TI - Progesterone-cortisol interaction in control of renin activity but not aldosterone. AB - In addition to its effect of inhibiting adrenocorticotropic hormone (ACTH) secretion, cortisol (hydrocortisone) inhibits the renin-angiotensin system in both fetal and adult sheep. We have found that progesterone attenuates the inhibition of ACTH by cortisol. These studies test whether progesterone interacts with cortisol in control of the renin-angiotensin-aldosterone system. Conscious adult ewes were infused with vehicle, cortisol (4 micrograms.kg-1.min-1), progesterone (0.5 microgram.kg-1.min-1), or cortisol with progesterone for 60 min. Beginning 120 min after the start of the infusion, renin secretion was stimulated by infusing sodium nitroprusside (10 micrograms.kg-1.min-1 iv). Cortisol infusion decreased plasma K+ concentration and reduced the plasma renin activity (PRA) and aldosterone responses to nitroprusside. Progesterone alone had no effect on PRA, aldosterone, or K+. Progesterone reduced the inhibition of PRA, but not aldosterone or K+, by cortisol. The data also indicate that the suppression of renin, as well as the suppression of ACTH, involves receptors or intracellular mechanisms with which progesterone interacts, whereas the inhibition of aldosterone involves a mechanism that progesterone does not affect. PMID- 2201220 TI - Relationship between thirst and diazoxide-induced hypotension in rats. AB - Diazoxide, a potent vasodilator and antidiuretic, was used to examine the relationship between hypotension and thirst in conscious rats with indwelling arterial and venous catheters. Bolus iv. injections (5-50 mg/kg) caused prompt, long-lasting, and dose-dependent reductions in mean arterial pressure (MAP) and stimulated drinking. Water intake and degree of hypotension were closely correlated when MAP was 10-65 mmHg below normal. At the time of drinking there were no significant changes in central venous pressure, plasma osmolality, or Na+ or K+ concentration. Plasma glucose increased approximately 35%, and blood volume increased approximately 10% (based on hematocrit changes and dilution of Evans blue). Captopril (100 mg/kg sc to block the renin-angiotensin system) enhanced the depressor response to diazoxide but abolished the dipsogenic response over the same range of arterial pressures tested in controls. Angiotensin II iv infusion restored drinking in captopril-treated animals. The combination of captopril and diazoxide did not block drinking to iv infusions of hypertonic saline or water deprivation. These results confirm that hypotension potently stimulates thirst and support the hypothesis that angiotensin II mediates the dipsogenic response in rats. PMID- 2201221 TI - Family functioning and major depression: an overview. AB - The authors review the evidence supporting the idea that the family plays a major role in the development and course of major depression. They find that the family pathology evident during an acute depressive episode continues after the patient's remission; that the course of depressive illness, relapse rates, and suicidal behavior are all affected by family functioning; and that children of depressed parents are at high risk for psychopathology. The authors explore unresolved issues regarding our understanding of the factors mediating the interaction between major depression and family functioning, concluding that there is evidence to support family and marital interventions, particularly in the treatment of depressed women. PMID- 2201222 TI - Variability in the application of contemporary diagnostic criteria: endogenous depression as an example. AB - Specified diagnostic criteria have been credited, in part, with improving diagnostic reliability. The authors hypothesize that nonuniform application of these criteria across different research centers has been one factor responsible for the failure to replicate research findings. For example, researchers using a narrow interpretation of the Research Diagnostic Criteria (RDC) have found a highly significant association between endogenous depression and a positive dexamethasone suppression test result, whereas researchers using a broad interpretation have failed to find the predicted relationship. The authors used two interpretations of the RDC and DSM-III endogenous/melancholia criteria to diagnose 60 depressed patients and found significant difference in rates of diagnoses and symptoms. PMID- 2201223 TI - Amoxapine versus amitriptyline combined with perphenazine in the treatment of psychotic depression. AB - In a double-blind study lasting for 4 weeks, the authors compared the effectiveness of amoxapine, an antidepressant with potential antipsychotic properties, with a combination of amitriptyline plus perphenazine in the treatment of 38 patients who had the diagnosis of major depression with psychotic features (psychotic or delusional depression). Patients in each group showed similar improvement in depression and psychosis. There was a tendency for the patients treated with amitriptyline plus perphenazine to have higher global response rates. However, the patients given amoxapine had significantly fewer extrapyramidal side effects. PMID- 2201224 TI - Evaluation of two formulations of dihydrocodeine using patient-controlled analgesia. AB - A randomised, double-blind study of 90 patients after cardiac bypass surgery was undertaken to assess the relative analgesic efficacies of normal- and controlled release oral dihydrocodeine. Patients received either placebo, normal-release dihydrocodeine, or controlled-release dihydrocodeine at regular intervals on the first to third days after operation. This was supplemented in all groups by intravenous morphine administered on demand by a patient-controlled analgesia system. Morphine requirements in the control group were significantly greater during this 48-hour period than in either of the active groups (p less than 0.01), but there was no statistically significant difference between the two active preparations. PMID- 2201225 TI - Comparison of intramuscular ketorolac and morphine in pain control after laparotomy. AB - Ketorolac, a prostaglandin synthetase-inhibiting analgesic, was compared with morphine for relief of pain after laparotomy for gynaecological surgery. Eighty patients were studied; they were given either ketorolac 30 mg intramuscularly followed by 10 mg 4-hourly as required, or morphine 10 mg intramuscularly 4 hourly as required, administered in a double-blind, randomised fashion. Pain scores (verbal and visual analogue) were recorded at baseline and assessed at 30 and 60 minutes and then hourly for 6 hours. Pain relief was measured at the same times. Pain and pain-relief scores were further assessed on the evening of day 1 and at 24 hours. Pain scores were similar in the two groups but pain-relief scores were better in the morphine group. A considerable number of patients suffered postoperative nausea and vomiting but there was no difference between the groups. One patient in the ketorolac group had unexplained hypotension. It is concluded that ketorolac can provide effective postoperative analgesia. PMID- 2201226 TI - Postoperative hypoxaemia: mechanisms and time course. AB - Postoperative hypoxaemia results predominantly from two mechanisms. Gas exchange is impaired during anaesthesia as a result of reduced tone in the muscles of the chest wall and probably alterations in bronchomotor and vascular tone, and the resulting changes persist into the postoperative period. In addition, there is an abnormality of control of breathing, which results in episodic obstructive apnoea. These episodes continue for several days after operation and are related to sleep pattern and analgesic administration, although the precise effects of different analgesic regimens have not been evaluated. Oxygen administration is effect in reducing the degree of hypoxaemia. PMID- 2201227 TI - [The bowel as an ischemic organ]. AB - Due to the progress that has been made in intensive care, more and more patients survive shock. It is a clinical observation that their condition improves substantially with the restoration of intestinal function. Different experimental models have been developed to investigate the pathophysiology of the intestine in shock. As noxious periods, both the phase of ischemia and the phase of reperfusion have been identified. Since the experimental models are methodologically very different, the results of the various studies may only be compared with reservations. Nevertheless, it can be stated that reduced intestinal blood flow leads to ischemia and hypoxia of the villous tips. Reperfusion may lead to further mucosal injury. During this period oxygen free radicals and their derivates seem to play an essential role. Xanthine oxidase is thought to be the major source of these radicals in the small intestine. During ischemia ATP is catabolized to hypoxanthine, which is enzymatically transformed to xanthine, a process generating oxygen free radicals. Moreover oxygen free radicals seem to be produced by activated neutrophilic granulocytes. At present, only hypotheses exist concerning the interactions between granulocytes and these radicals. The mechanism of injury produced by oxygen free radicals is based on the peroxidation of the lipid components of the cellular membrane system. The small intestine represents a very vulnerable shock organ: apart from its very important nutritive functions, it provides the necessary barrier between the intestinal pool of endotoxin and the circulation. The loss of these vital functions due to ischemic lesions dramatically worsens the chances for the patient to survive. Therefore, it is necessary to develop therapeutic principles to maintain or restore intestinal function in shock. PMID- 2201228 TI - Comparison of DNA:DNA homology and enzymatic activity between Pasteurella haemolytica and related species. AB - A commercially available microbiological identification system and DNA:DNA hybridization were used to determine relationships between and within serovars 1 13 of Pasteurella haemolytica, and between P haemolytica and P multocida and 4 species of Actinobacillus. All serovars of P haemolytica that belonged to biovar A were related with mean DNA homology of 78%, whereas all serovars of P haemolytica that belonged to biovar T were related to each other with mean DNA homology of 90%. The DNA:DNA hybridization between strains of biovars A and T ranged from 3 to 13%, indicating little or no genetic relationship between the 2 biovars of P haemolytica. The DNA homology between all serovars of P haemolytica and other species of non-P haemolytica bacteria tested (P multocida and actinobacilli) was less than 14%, suggestive of essentially no genetic relationship of P haemolytica with the ATCC reference strains of the genus Pasteurella or the genus Actinobacillus. Enzymatic differences were observed between P haemolytica and the other non-P haemolytica bacteria tested; however, the microbiological identification system that uses enzymatic reactions could not distinguish among biovars of P haemolytica. Results of this research support other data that suggest that biovars A and T of P haemolytica should be classified as separate species, but do not support the inclusion of either biovar A or T within the genus Actinobacillus. PMID- 2201229 TI - Effects of preweaning exposure to a starter diet on enterotoxigenic Escherichia coli-induced postweaning diarrhea in swine. AB - Experiments were conducted to evaluate the effect of restricted feeding of a starter diet to suckling pigs (creep feeding) in a model of postweaning colibacillosis. The hypothesis that restricted creep feeding primes an intestinal allergic reaction to starter diet ingested after weaning was tested. Twenty-eight suckling pigs were fed a starter diet for 3 h/d on days 7, 8, and 9 after birth (creep-fed). Twenty-six suckling pigs were not fed the diet until 3 weeks of age (not creep-fed), when all pigs were weaned and given the starter diet. One day after weaning, 24 creep-fed and 22 not creep-fed pigs were inoculated with K88+ enterotoxigenic Escherichia coli, and 4 pigs in each group were kept as noninoculated controls. Among inoculated pigs (principals), 10 creep-fed and 12 not creep-fed pigs were found to be genetically resistant to K88+ E coli and remained healthy during the 6-day postinoculation period, as did the noninoculated controls. Eighteen (10 creep-fed and 8 not creep-fed) of the 24 genetically susceptible principals developed diarrhea after inoculation. There were no significant differences in the incidence and severity of diarrhea, amount of body weight loss, and mortality between creep-fed and not creep-fed susceptible principal pigs. Histologic examination of intestine from control pigs and principals that survived for 6 days after infection did not reveal any substantial morphologic difference between creep-fed and not creep-fed groups. In conclusion, creep feeding was not required for the production of diarrhea in this model. Creep feeding did not induce morphologic changes characteristic of an allergic reaction in the small intestine. PMID- 2201230 TI - Cardiovascular and respiratory effects of inspired oxygen fraction in halothane anesthetized horses. AB - Anesthesia of equids is associated with pulmonary dysfunction. Cardiovascular and respiratory effects of inhalation anesthetic agents and duration of anesthesia have been studied, using oxygen as the carrier gas. To our knowledge, the effects of inspired oxygen have not been determined. We studied the cardiovascular and respiratory effects of 2 inspired oxygen fractions (0.30 and greater than 0.85) in 5 laterally recumbent, halothane-anesthetized horses. Mean systemic arterial blood pressure, cardiac output, central venous pressure, pulmonary arterial pressure, arterial pH, and arterial base excess were similar in horses of the 2 groups during 4 hours of anesthesia at constant end-tidal halothane concentration. End-tidal partial pressure of CO2, arterial partial pressure of CO2 and O2, and alveolar-to-arterial O2 tension difference were greater in horses exposed to the higher oxygen concentration. On the basis of the data obtained, we suggest that greater hypoventilation and ventilation/perfusion mismatch occur when horses are breathing high-oxygen fraction. Arterial partial pressure of O2 was not different between the 2 groups of horses after they were disconnected from the anesthesia circuit and allowed to breathe room air. Horses recovered from anesthesia without complications. PMID- 2201231 TI - Nephrotomography and ultrasonography for the localization of hyperfunctioning adrenocortical tumors in dogs. AB - Nephrotomography and ultrasonography were used in 11 dogs with hyperadrenocroticism to assess the value of these techniques for the localization of biochemically diagnosed hyperfunctioning adrenocortical tumors. Both techniques enabled accurate localization of a unilateral adrenal mass in each of the dogs. Cross-sectional diameters of the masses ranged from 1 to 4 cm. In 1 dog, expansion of tumor into the caudal vena cava was revealed by caudal venacavography and ultrasonography. Mineralization in the tumor mass in 2 dogs was easily recognized by nephrotomography, but not by ultrasonography. Paracostal laparotomy confirmed the presence of an adrenocortical tumor in each dog, and expansion of tumor into the caudal vena cava in 1 dog. Cross-sectional diameters of the tumors ranged from 1.2 to 4.5 cm and corresponded well with cross sectional measurements by nephrotomography and ultrasonography. It was concluded that nephrotomography and ultrasonography have similar diagnostic accuracies for the detection and localization of hyperfunctioning adrenocortical tumors. PMID- 2201232 TI - Treating hyponatremia: what is all the controversy about? PMID- 2201233 TI - Practicing health promotion: the doctor's dilemma. PMID- 2201234 TI - The aging process. AB - The intricate cause of the aging process in humans and animals, at present a matter of intense speculation, has given rise to many theories. Despite its uncertain cause, aging constitutes the most significant and universal problem confronting physicians today. Age-related physiologic deterioration and age associated diseases are of immense concern to physicians because of the "old-age boom" anticipated in the first part of the twenty-first century. Biomedical research achievements in the twentieth century have permitted more persons to approach the fixed upper limit of the human lifespan. We discuss the functional decline of the aging heart and the underlying mechanisms of that decline; quantitative and qualitative changes in the immune system; and normal aging of the human brain contrasted to the brain changes seen in Alzheimer disease. With our growing geriatric population, we greatly need to increase our understanding of both the causes of human aging and the goals of gerontology and geriatrics and to expand research into the significant problem of Alzheimer disease. PMID- 2201235 TI - Managing medical references. PMID- 2201236 TI - Pavlov and his neurological investigations of the viscera. PMID- 2201237 TI - Brain regulation of gastric acid secretion by peptides. Sites and mechanisms of action. PMID- 2201238 TI - Hans Selye and the concept of biologic stress. Ulcer pathogenesis as a historical paradigm. PMID- 2201239 TI - Proactive actions of psychological stress on gastric ulceration in rats--real psychobiology. PMID- 2201240 TI - Limbic system modulation of stress ulcer development. PMID- 2201241 TI - The role of the hypothalamic-pituitary-thyroid axis in stress gastric ulcers. PMID- 2201242 TI - Prolactin as a protective factor in stress-induced gastric ulcers. PMID- 2201243 TI - Central nervous system regulation of gastrointestinal motility. PMID- 2201244 TI - The role of corticotropin-releasing factor in rat gastric ulcerogenesis. PMID- 2201245 TI - Mediation of gastrointestinal stress responses by corticotropin-releasing factor. PMID- 2201246 TI - Modification of Livaditis' myotomy for long gap oesophageal atresia. AB - A modification of Livaditis' myotomy to bridge a long gap oesophageal atresia is presented. The wide hypertrophic oral segment is lengthened with several horizontal incisions through the muscle layer. These incisions are made in a network of several rows without perforating the mucosa. The thick, broad oral segment becomes longer and narrower and fits better for anastomosis with the smaller distal segment. Pocket formations and diverticula can thus be avoided. PMID- 2201247 TI - Fibronectin in the ruptured human Achilles tendon and its paratenon. An immunoperoxidase study. AB - The purpose of the present study was to examine the role and distribution of fibronectin--a major connective tissue protein--in normal and ruptured Achilles tendon and its paratenon using peroxidase antiperoxidase (PAP) method and conventional histology. Samples were taken intraoperatively 6 to 48 hours after rupture from 30 patients, and 4 male cadavers served as controls. In controls fibronectin could not be detected in the tendinous connective tissue or in the areolar tissue of the paratenon. In the ruptured tendons fibronectin was detected around the tenocytes and in the collagen fibres in the necrotic and mucinous degenerated areas, but also in the macroscopically healthy areas of the tendon. In the oedematous paratenon vascular walls were rich in fibronectin and fat cells were outlined by fibronectin. Areas of homogenous deposition of fibronectin were also frequently seen in the paratenon. A vast amount of fibronectin was observed also at the site of rupture. The present results indicate that there are striking changes in the composition of connective tissue in degenerated tendon and paratenon. These changes seem to have increased susceptibility of the tendon to rupture. PMID- 2201248 TI - Antimicrobial susceptibility of Haemophilus ducreyi. PMID- 2201249 TI - Treatment of chancroid. PMID- 2201250 TI - Comparative activities of several nucleoside analogs against duck hepatitis B virus in vitro. AB - Duck hepatitis B virus (DHBV) replication in primary duck hepatocytes was monitored by examining the synthesis of both DHBV DNA and DHBV core antigen. Several nucleoside analogs which were previously shown to inhibit the replication of DNA viruses (i.e., herpesviruses) and retroviruses were examined for their inhibitory effects on the synthesis of DHBV core antigen in primary duck hepatocytes. (S)-9-(3-Hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], 9-(2 phosphonylmethoxyethyl)-2,6-diaminopurine, 2',3'-dideoxyadenosine, and 2',3' dideoxycytidine inhibited DHBV core antigen synthesis at concentrations that were significantly lower than those found to be toxic to the primary hepatocytes. Of all the compounds tested, (S)-HPMPA showed the lowest 50% effective concentration (0.5 micrograms/ml). The selectivity index or ratio of the 50% cytotoxic concentration to the 50% effective concentration of (S)-HPMPA was greater than 300. (S)-HPMPA not only inhibited DHBV core antigen but also DHBV DNA synthesis in DHBV-infected hepatocytes. PMID- 2201251 TI - Involvement of a cell wall receptor in the mode of action of an anti-Candida toxin of Pichia anomala. AB - Hanes-Woolf, Dixon, and Hill plots of growth rates of Candida albicans RC1 grown in various concentrations of glucose and a Pichia anomala WC65 toxin suggested the presence of toxin-binding sites. Indirect immunofluorescence microscopy with antitoxin antibodies demonstrated binding of the toxin to the cell wall. Resistance to the toxin of a mutant Saccharomyces cerevisiae deficient in cell wall beta-1-6-D-glucan suggests that the glucan either served as the receptor or influenced the number or composition of the receptor. Immunofluorescence that appeared to be associated with the cell membrane of toxin-treated spheroplasts of C. albicans was also observed. Spheroplasts of the resistant mutant of S. cerevisiae were sensitive to the toxin. PMID- 2201252 TI - Ceftazidime versus imipenem-cilastatin as initial monotherapy for febrile neutropenic patients. AB - One hundred febrile episodes in 89 neutropenic patients after cytotoxic chemotherapy were randomized to be treated with either ceftazidime or imipenem as initial monotherapy. The clinical characteristics of the two groups of patients were comparable. The response of the fever in patients who received imipenem was significantly better than that in those who received ceftazidime (77 versus 56%, respectively; P = 0.04), especially in those with microbiologically documented infection (81 versus 33%, respectively; P = 0.02). The in vitro susceptibilities and the clinical responses suggested that, with the possible exception of Pseudomonas spp., imipenem was more effective than ceftazidime in treating neutropenic infections caused by both gram-positive and -negative organisms. An additional 23 and 21% of the patients in the ceftazidime and imipenem groups, respectively, responded to the addition of cloxacillin and amikacin following failure of monotherapy. The majority of the treatment failures, relapses, and superinfections were related to resistant infective organisms such as methicillin resistant Staphylococcus spp. and Pseudomonas spp. or disseminated fungal infections. PMID- 2201254 TI - Structure-activity relationships of analogs of pentamidine against Plasmodium falciparum and Leishmania mexicana amazonensis. AB - The antiprotozoal compound 1,5-di(4-amidinophenoxy)pentane (pentamidine) and 36 of its analogs were screened for in vitro activity against Leishmania mexicana amazonensis clone 669 C4S (MHOM/BR/73/M2269) and Plasmodium falciparum clones W2 (Indochina III/CDC) and D6 (Sierra Leone I/CDC). Pentamidine and each of the analogs tested exhibited activity in vitro against L. m. amazonensis and P. falciparum. The pentamidine analogs were more effective against the P. falciparum clones than against L. m. amazonensis. P. falciparum was extremely susceptible to these compounds, with 50% inhibitory concentrations as low as 0.03 microM. While none of the analogs exhibited marked improvement in antileishmanial activity compared with pentamidine, 12 of the pentamidine analogs showed activity approximately equal to or greater than that of the parent compound. From the promising activity exhibited by the pentamidine analogs in this in vitro study and their potential for reduced toxicity relative to the parent drug, pentamidine related compounds hold promise as new agents for the treatment of protozoal infections. PMID- 2201253 TI - Sequence analysis and evolutionary perspectives of ROB-1 beta-lactamase. AB - The nucleotide sequence of the ROB-1 beta-lactamase gene from Haemophilus influenzae plasmid RRob was determined. The structural gene encodes a polypeptide of 305 amino acids, with an estimated molecular mass of 30,424 for the mature form of the protein. The ROB-1 gene showed low homologies with other beta lactamases at the nucleic acid level. By using two statistical computer methods, assessment of the extent of similarity between ROB-1 and other known beta lactamase amino acid sequences suggested that ROB-1 is a class A enzyme. Alignment of class A beta-lactamases with ROB-1 identified conserved residues. The use of a mutation matrix for detecting distance relationships indicated that ROB-1 has higher values and homologies with beta-lactamases of gram-positive bacteria, giving insight into its ancestry and divergence. PMID- 2201255 TI - In vitro susceptibilities of Plasmodium falciparum to compounds which inhibit nucleotide metabolism. AB - A unique metabolic feature of malaria parasites is their restricted ability to synthesize nucleotides. These parasites are unable to synthesize the purine ring and must therefore obtain preformed purine bases and nucleosides from the host cell, the erythrocyte. On the other hand, pyrimidines must be synthesized de novo because of the inability of the parasites to salvage preformed pyrimidines. Thus, one would anticipate that the blockage of purine salvage or pyrimidine de novo synthesis should adversely affect parasite growth. This premise was tested in vitro with a total of 64 compounds, mostly purine and pyrimidine analogs, known to inhibit one or more steps of nucleotide synthesis. Of the 64 compounds, 22 produced a 50% inhibition of the growth of the human malaria parasite Plasmodium falciparum at a concentration of 50 microM or less. Inhibition of the growth of chloroquine-resistant clones of P. falciparum did not differ significantly from that of the growth of chloroquine-susceptible clones. Two of the compounds which effectively inhibited parasite growth, 6-mercaptopurine and 6-thioguanine, were found to be potent competitive inhibitors of a key purine-salvaging enzyme (hypoxanthine-guanine-xanthine phosphoribosyltransferase) of the parasite. PMID- 2201256 TI - Randomized, double-blind trial of 1- versus 4-hour amphotericin B infusion durations. AB - We conducted a randomized, double-blind trial of 1- versus 4-h infusions of amphotericin B to determine whether there was any difference in infusion-related toxicity. A total of 128 maintenance infusions in 12 patients were studied; 62 were randomized to 1-h infusions (group A) and 66 were randomized to 4-h infusions (group B). We found no significant differences between patients in groups A and B in mean temperature, pulse, or systolic or diastolic blood pressure measured during the infusions. At a significant level of 0.05, the power to detect a mean difference in temperature of 2 degrees C, a pulse difference of 20 beats per min, a decrease in diastolic blood pressure of 10 mm Hg, or a decrease in systolic blood pressure of 20 mm Hg was 0.95. Rigors and chills were noted in 15 of 62 (24.1%) infusions in group A patients and 12 of 66 (18.1%) infusions in group B patients (P = 0.40). Meperidine was required because of severe persistent rigors in 6 of 62 (9.6%) infusions in group A patients and 6 of 66 (8.9%) infusions in group B patients (P = 0.91). An increase in temperature was noted in five (8%) of the group A infusions and seven (10.6%) of the group B infusions (P = 0.63). The mean time to onset of rigors, an increase in temperature, and an increase in pulse occurred significantly earlier in group A than in group B patients (P = 0.02 for all comparisons). We conclude that there is no difference in the incidence or severity of the infusion-related toxicity of amphotericin B with a 1-h infusion rate compared with a 4-h infusion rate. However, the onset of infusion-related toxicity occurs significantly earlier with a 1-h infusion. PMID- 2201257 TI - Risk factors for fecal colonization with trimethoprim-resistant and multiresistant Escherichia coli among children in day-care centers in Houston, Texas. AB - In a previous study, we found fecal colonization with multiresistant Escherichia coli exhibiting high-level trimethoprim resistance in 19% of diapered children attending six day-care centers in Houston, Tex. To examine the potential risk factors associated with this finding, we conducted cross-sectional studies among 203 children attending 12 day-care centers, 51 children attending a well-child clinic (controls), and 64 medical students. The prevalence of fecal colonization with trimethoprim-resistant E. coli among children attending day-care centers (30%) was higher (P less than 0.001) than among control children (6%) or medical students (8%). The prevalence of colonization among the children attending the 12 centers ranged from 0 to 59% and was correlated with the number of diapered children enrolled (r = 0.73; P less than 0.01). In a case control study among the day-care center children, significant risk factors were an age of less than 12 months and attendance at a center with an enrollment of over 40 diapered children (odds ratios of 2.2 and 3.5, respectively); ethnicity, duration of attendance, and prior antibiotic administration were not associated with colonization. Plasmid analysis of 60 of the day-care center strains revealed 22 profiles, each of which was unique to a given day-care center. Transmission and carriage of trimethoprim-resistant strains for as long as 6 months was documented in one center studied on three occasions. Given the documented transmission of enteric pathogens among diapered children attending day-care centers and their spread into family members, it is likely that day-care centers are an important community reservoir of plasmid-associated antibiotic-resistant E. coli. PMID- 2201258 TI - In situ enzyme-linked immunosorbent assay to quantitate in vitro development of Eimeria tenella. AB - An in situ enzyme-linked immunosorbent assay was developed to measure in vitro development of Eimeria tenella. The assay used a polyclonal, anti-merozoite serum produced by immunization with culture-derived, chromatographically purified merozoites. Although this antiserum cross-reacted with sporozoite-infected cultures (by indirect immunofluorescence and in situ enzyme-linked immunosorbent assay), it clearly distinguished the increase in antigen synthesized throughout intracellular growth. The assay can be used for high-throughput, anticoccidial drug screening, for which it gives quantitative results that are comparable to the published radiometric [( 3H]uracil incorporation) endpoint. PMID- 2201259 TI - Nucleotide sequence of SHV-2 beta-lactamase gene. AB - The nucleotide sequence of plasmid-mediated beta-lactamase SHV-2 from Salmonella typhimurium (SHV-2pHT1) was determined. The gene was very similar to chromosomally encoded beta-lactamase LEN-1 of Klebsiella pneumoniae. Compared with the sequence of the Escherichia coli SHV-2 enzyme (SHV-2E.coli) obtained by protein sequencing, the deduced amino acid sequence of SHV-2pHT1 differed by three amino acid substitutions. PMID- 2201260 TI - New insights into the haemolytic uraemic syndromes. PMID- 2201261 TI - Haemolytic uraemic syndromes in the British Isles 1985-8: association with verocytotoxin producing Escherichia coli. Part 1: Clinical and epidemiological aspects. AB - A prospective study of the clinical and epidemiological features of the haemolytic uraemic syndromes was conducted over a three year period in the British Isles. Two hundred and ninety eight children were reported. In two thirds of cases stool samples were analysed for the presence of Verocytotoxin producing Escherichia coli (VTEC) and neutralisable Verocytotoxin. A total of 273 (95%) patients had a prodrome of diarrhoea. In these a seasonal variation in the incidence of haemolytic uraemic syndrome was demonstrated, the 1-2 year age range was most often affected, and the peripheral blood neutrophil count correlated positively with an adverse outcome. Patients presenting without diarrhoea showed none of these associations and had a significantly greater morbidity and mortality. Evidence for VTEC infection was found in 58 (33%) of 178 diarrhoea associated cases whose stools were analysed, although VTEC were identified in five of eight (62%) patients whose stools were collected within three days of the onset of diarrhoea. Most isolates produced VT2 either alone, or together with VT1. There was no evidence of VTEC infection in patients without prodromal diarrhoea. PMID- 2201263 TI - Markers of serious illness in infants under 6 months old presenting to a children's hospital. AB - Six hundred and eighty two assessments were performed on 641 babies under 6 months of age who presented to the emergency department of the Royal Children's Hospital, Melbourne, to try and determine the best markers of serious illness in young infants. Detailed, specific questions that quantified a baby's functional response to illness gave the most useful information. As a group, the six most common predictive symptoms of serious illness were: taking less than half the normal amount of feed over the preceding 24 hours, breathing difficulty, having less than four wet nappies in the preceding 24 hours, decreased activity, drowsiness, and a history of being both pale and hot. The presence of the corresponding sign on examination increased the predictive value of the symptom by 10-20%. Specific, highly predictive (though less common) signs included moderate to severe chest wall recession, respiratory grunt, cold calves, and a tender abdomen. A list of low, medium, and high risk symptoms has been constructed and the five measurements that were most useful in predicting serious illness in young infants have been detailed. PMID- 2201262 TI - Haemolytic uraemic syndromes in the British Isles, 1985-8: association with verocytotoxin producing Escherichia coli. Part 2: Microbiological aspects. AB - In a three year study of children under 16 years with haemolytic uraemic syndrome faecal samples were examined for the presence of Verocytotoxin producing Escherichia coli (VTEC) using DNA probes and for free neutralisable Verocytotoxin in a Vero cell assay with specific antisera. There was evidence of VTEC infection in 58 of 185 (31%) samples. A total of 53 VTEC was identified from patients with haemolytic uraemic syndrome. Thirty eight VTEC belonged to serotype O157:H7 or O157:H-, 34 produced VT2 only, and four strains produced both VT1 and VT2. The remaining 15 VTEC belonged to nine different O serogroups; three strains produced VT1, 10 produced VT2, and two were positive for VT1 and VT2. Three control groups of patients without haemolytic uraemic syndrome were also examined. There was evidence of VTEC infection in 8%, 6%, and 4% of specimens from individuals with bloody diarrhoea, those with diarrhoea only, and healthy controls respectively. VTEC from the bloody diarrhoeal and diarrhoeal controls were O157:H7 but those from the healty controls could not be O serogrouped. This study confirms the association of VTEC, and particularly strains of O157:H7, with haemolytic uraemic syndrome. Strains producing VT1, VT2, or both toxins were isolated, although over 94% of VTEC produced VT2 alone or together with VT1. PMID- 2201265 TI - Michael Parkin--an international paediatrician. PMID- 2201264 TI - Evaluating screening tests and screening programmes. PMID- 2201267 TI - Sonographic and pathological features of callosal hypoplasia in non-ketotic hyperglycinaemia. AB - A boy was born at 36 weeks' gestation weighing 2450 g. Though his Apgar score was 9 at birth, by the age of 48 hours he required artificial ventilation. He was deeply unconscious with complete lack of muscle tone, and non-ketotic hyperglycinaemia associated with secondary hypoplasia of the corpus callosum was confirmed by biochemical tests. The cranial ultrasound scan features correlated well with the neuropathological findings and may be helpful in the early detection of this incurable condition. PMID- 2201266 TI - Follow up of premature babies treated with artificial surfactant (ALEC). AB - Of 235 survivors who had taken part in a randomised trial of artificial surfactant and who were born in Cambridge, follow up information was available for 231 (98%) infants. In 12 cases information came from local doctors; all others were assessed at 9 and 18 months (n = 212) or 9 months only (n = 7). There was no difference between those who had been treated with surfactant and control babies in the incidence of neurological impairment, mental impairment, respiratory infections, allergies, or hospital admissions up to 18 months after full term. In those born before 30 weeks' gestation (where surfactant most improves survival) the number of surviving randomised children who were normal was 35 of 61 in the treated group (57%) compared with 25 of 61 in the control group (41%). Improved neonatal survival after prophylactic surfactant treatment is not associated with an increased incidence of neurodevelopmental impairment. PMID- 2201268 TI - Reproducibility of cerebral artery Doppler measurements. AB - Intraobserver and interobserver variability were calculated for the measurement of cerebral artery pulsatility indices by five observers who made two recordings on each of 12 stable preterm infants. Variations in pulsatility indices of up to 0.21 were found; no measurement was below 0.55. PMID- 2201269 TI - Charles-Michel Billard (1800-1832): pioneer of neonatal medicine. PMID- 2201270 TI - [List of scientific publications by Heinz Rohrer]. PMID- 2201271 TI - [New types of virus infections of domestic animals in the German Democratic Republic. 4. Tahyna virus infections--a review]. AB - A general account is given in this paper of history, incidence, pathogen properties, morphogenesis, isolation, and culturing of Tahyna virus. Reference is also made to methods for detection, host spectrum, immunity, epizootiology, pathogenesis, and clinical symptoms in man and animals and also to aspects relating to pathological anatomy as well as to regular and differential diagnosis. PMID- 2201272 TI - [Preliminary results of the determination of plasmid profiles of veterinary Salmonella isolates]. AB - A plasmid of 60 Md magnitude was recorded from 40 in 41 Salmonella (S.) typhimurium strains, including the Copenhagen minus variant. A plasmid of that kind had been described in the international literature as serovar-specific of S. typhimurium. One S. typhimurium strain was without plasmid. Five contained the 60 Md and other plasmids. No relationship was found to exist between the 60-Md plasmid and biovar as well as chemotherapeutic resistance. Further studies will be necessary for consistent information on virulence association of this plasmid and its serovar specificity. Plasmid profiles were also checked in four S. enteritidis strain and additional serovars. PMID- 2201273 TI - Phosphorylation of cytochrome P450 isoenzymes in intact hepatocytes and its importance for their function in metabolic processes. AB - Recent data show that besides the well-known long-term regulation of cytochrome P450-dependent monooxygenase activity by induction there also exists a fast regulation by phosphorylation. This phosphorylation occurs when purified cytochromes P450 are combined with purified protein kinases, and also in intact cells. This process is donor- and acceptor-selective leading to phosphorylation of defined isoenzymes by defined protein kinases. This in turn leads to fast and marked changes in metabolism which are selective for given substrates and regio- and stereo-selective for given positions. This in turn is selectively and differentially influenced by the individual control of the protein kinase in question. PMID- 2201274 TI - Effect of glucose in mice after acute experimental poisoning with arsenic trioxide (As2O3). AB - Carbohydrate depletion (glucose and glycogen) was reported to be a major problem in acute arsenic poisoning. In the present paper the effectiveness of glucose substitution was investigated in mice after acute experimental poisoning with As2O3. Four groups of ten mice each received As2O3, 12.9 mg/kg, s.c. After the injection the first group remained without further treatment, the second received saline every 2 h, the third 5% glucose, and the fourth 5% glucose +0.12 IE insulin/kg i.p. Groups 5 and 6, five mice each, received either saline or glucose only. Group 7, five mice, remained without any treatment. Immediately after death the livers were removed for the enzymatic determination of glucose and glycogen. Mice receiving As2O3 only died within 22 h. The mean survival time was 12.4 h. In mice receiving As2O3 and after that saline, glucose, or glucose + insulin, an increase in the survival time to 30.8, 40.7, and 43.6 h, respectively, was observed. All mice which died showed a significant decrease in the liver glucose and glycogen content, compared to control animals. In livers of survivors, the glucose and glycogen content was not different to the control groups. The data support the assumption that carbohydrate depletion is an important factor in arsenic toxicity, and its substitution should be considered in the treatment of arsenic poisoning. PMID- 2201275 TI - [Apo B, fibrinogen-fibrin and fibronectin in the intima of the normal human aorta and large arteries and in atherosclerosis]. AB - Apo B, fibrinogen/fibrin, fibronectin, thrombocytes, factor VIII of the blood coagulation and smooth muscle cells (SMC) were identified by the immunofluorescence method in the intima of aorta and big arteries under normal conditions and in atherosclerosis. Monoclonal antibodies (MCA) against C-end fragments of A alpha-fibrinogen chain were used in the study of fibrinogen/fibrin. MCA reacting with plasma fibronectin and those reacting with A area of the polypeptide chain specific for the cell fibronectin were used for the identification of fibronectin. Small amount of fibrinogen/fibrin, no fibronectin in the extracellular matrix and the cell fibronectin around SMC were observed on the normal intima and lipid strip in spite of the presence of Apo B. The results indicate that fibrinogen/fibrin is accumulated in the plaques due to the incorporation of the wall thrombi, insudation from the blood plasma, intramural haemorrhages as well as around cells, presumably macrophages. PMID- 2201276 TI - [The prospective directions of research in teratology]. AB - Unsolved problems of modern teratology are discussed. The monitoring of the congenital malformation incidence is one of the variants of evaluation and control of the mutation pressing in the population. The investigation of human foetuses obtained in artificial abortions may be very helpful in this respect. The investigation of the phenotypical manifestations of malformations in the human prenatal ontogenesis and the use of the results for the creation of notion on the malformation morphogenesis seems to be perspective. The definition of the tissue dysplasias and their classification (dystopia, dyssynchronia, hamartomas) are given. The issue of the tissue malformations during the postnatal development is not similar. They may be asymptomatic, or to disturb the function of the organ concerned, or to predispose to chronic inflammation or neoplastic growth. PMID- 2201277 TI - [Pathological anatomy in the Mongolian People's Republic: the stages in its development]. PMID- 2201278 TI - [The morphofunctional characteristics of the microvascular endothelium and other structural elements of the lung in the development of gram-negative infection]. AB - An early response (activation) of the microcirculatory bed endothelial cells precedes other changes in the lung in the course of development of gram-negative infection. This response is manifested at various degree in different endotheliocytes and taking into consideration the microenvironment (alveolar macrophages, stromal elements, etc) is one of the main mechanisms in the development of infectious process. PMID- 2201279 TI - Rapid decompression to 50,000 feet: effect on heart rate response. AB - Interest in Molecular Sieve Oxygen Generation Systems (MSOGS) for use in military aircraft has demonstrated a need to study physiological effects of MSOGS product gas in the worst case scenario, a rapid decompression (RD). In this paper we report the heart rate (HR) response to positive pressure breathing (PPB) during and after RD from 6,096 to 15,239 m (20,000 to 50,000 ft) in a hypobaric chamber while breathing gas mixtures that simulate the product gas from MSOGS. Interbeat (R-R) intervals were recorded in 10 subjects while they breathed either Aviators' Breathing Oxygen (ABO), that is 99.5% oxygen, or 93% oxygen at two regulator settings: dilution and non-dilution. Additional experimental profiles on six subjects isolated the effects of hypoxia, anxiety, and PPB on HR changes after RD. Anxiety appeared to have the greatest effect. Most of the subjects showed increased HR and reduced HR variability after the onset of pressure breathing (immediately after decompression). As the exposure continued, HR variability increased as the HR began to decline. No consistent change in the HR response could be attributed to the modest increase in hypoxia produced by substitution of 93% oxygen for ABO. PMID- 2201280 TI - [Multi-morbidity and perioperative risk of total hip endoprosthesis]. AB - Paper describes the worldwide first-time implantation of an artificial joint by Themistocles Gluck (1853-1942) in May, 22 th 1890 in Berlin. After that in a retrospective study are represented multimorbidity and perioperative complications of 2,000 patients with total hip joint replacement performed between 1979 and 1987. The fatality was 1.6%, the rate of fatal lung-embolism 1.85%. Value of actual thromboembolism-prophylaxis and intensive-care-unit is discussed. PMID- 2201281 TI - [Results of surgical therapy of patellar chondropathy]. AB - 150 knees were re-examined after operative therapy because of chondromalacia patellae. We found good and very good results in 52.7%. The results after lateral release were statistically significant better than the results after after the other methods. Because of 82% good results the lateral release operation can be recommended. PMID- 2201282 TI - [Historical aspects of the therapy of supracondylar humerus fractures]. AB - Historical review in treatment of supracondylar numerous fractures. The treatment of fracture of the supracondylar humerus is already published in the antiquity. The statistic of medical attendance demonstrates, that the most authors claim the arrangement of the fracture immediately by extension of the forearm in inflexion of 90 grade. The best retention is the immobility of the arm by inflexion of 90 grade. Moreover it is necessary to inspection daily and if required the new reposition. Today the historical aspects instruct, the most frequent treatment is the extension at the right-angled flexed forearm and the retention in the same position. PMID- 2201283 TI - [The scientific achievement of surgeon Ernst von Bergmann (1836-1907) in the development of medicine in reference to his correspondence in the years 1877 1878]. AB - The scientific achievements of the surgeon Ernst von Bergmann (1836-1907) for the development of medicine in reflection to his letters between 1877 and 1878. The name of Ernst von Bergmann is connected closely with the history of the university of Berlin. Because of his dedicated work and his outstanding achievements in the filed of medicine he be came the leading representative of German surgery at the end of the 19. century. He obtained special international reputation by his scientific, sanitary-political and military-surgery activity in the time of the Bulgarian war of liberation (1877-1878). His letters and writings enable the reader nowadays to complete the hitherto existing picture of Ernst von Bergmann by new aspects. PMID- 2201285 TI - Sequence of cDNA for rat cystathionine gamma-lyase and comparison of deduced amino acid sequence with related Escherichia coli enzymes. AB - A cDNA clone for cystathionine gamma-lyase was isolated from a rat cDNA library in lambda gt11 by screening with a monospecific antiserum. The identity of this clone, containing 600 bp proximal to the 3'-end of the gene, was confirmed by positive hybridization selection. Northern-blot hybridization showed the expected higher abundance of the corresponding mRNA in liver than in brain. Two further cDNA clones from a plasmid pcD library were isolated by colony hybridization with the first clone and were found to contain inserts of 1600 and 1850 bp. One of these was confirmed as encoding cystathionine gamma-lyase by hybridization with two independent pools of oligodeoxynucleotides corresponding to partial amino acid sequence information for cystathionine gamma-lyase. The other clone (estimated to represent all but 8% of the 5'-end of the mRNA) was sequenced and its deduced amino acid sequence showed similarity to those of the Escherichia coli enzymes cystathionine beta-lyase and cystathionine gamma-synthase throughout its length, especially to that of the latter. PMID- 2201284 TI - The regulation and cellular functions of phosphatidylcholine hydrolysis. PMID- 2201287 TI - Non-uniform influence of transforming growth factor-beta on the biosynthesis of different forms of small chondroitin sulphate/dermatan sulphate proteoglycan. AB - The influence of transforming growth factor-beta (TGF-beta) on the expression of different forms of small proteoglycans was investigated in human skin fibroblasts and in a human osteosarcoma cell line. TGF-beta was not found to act as a general stimulator of small proteoglycan biosynthesis. In both cell types, an increased expression of the core protein of proteoglycan I was found. However, there was a profound decrease in the expression of a 106 kDa core protein, and either no alteration or a small decrease in the biosynthesis of the collagen-binding small proteoglycan II core protein. These results show that the production of individual members of the small proteoglycan family is differentially regulated. PMID- 2201286 TI - Overexpression of restructured pyruvate dehydrogenase complexes and site-directed mutagenesis of a potential active-site histidine residue. AB - The aceEF-lpd operon of Escherichia coli encodes the pyruvate dehydrogenase (E1p), dihydrolipoamide acetyltransferase (E2p) and dihydrolipoamide dehydrogenase (E3) components of the pyruvate dehydrogenase multienzyme complex (PDH complex). A thermoinducible expression system was developed to amplify a variety of genetically restructured PDH complexes, including those containing three, two, one and no lipoyl domains per E2p chain. Although large quantities of the corresponding complexes were produced, they had only 20-50% of the predicted specific activities. The activities of the E1p components were diminished to the same extent, and this could account for the shortfall in overall complex activity. Thermoinduction was used to express a mutant PDH complex in which the putative active-site histidine residue of the E2p component (His-602) was replaced by cysteine in the H602C E2p component. This substitution abolished dihydrolipoamide acetyltransferase activity of the complex without affecting other E2p functions. The results support the view that His-602 is an active-site residue. The inactivation could mean that the histidine residue performs an essential role in the acetyltransferase reaction mechanism, or that the reaction is blocked by an irreversible modification of the cysteine substituent. Complementation was observed between the H602C PDH complex and a complex that is totally deficient in lipoyl domains, both in vitro, by the restoration of overall complex activity in mixed extracts, and in vivo, from the nutritional independence of strains that co-express the two complexes from different plasmids. PMID- 2201289 TI - Extracellular control of erythrocyte metabolism mediated by a cytoplasmic tyrosine kinase. AB - We wish to propose a new mechanism of metabolic regulation mediated by a cytoplasmic tyrosine kinase. Briefly, as Steck et al. have shown, we propose that glyceraldehyde-3-phosphate dehydrogenase (G3PDH) associates reversibly with the N terminus of the cytoplasmic domain of band 3. Once the enzyme is bound, it is totally inhibited; however, upon release it is restored to full activity. We demonstrate that control of enzyme binding and consequently the glycolytic flux through this control point is executed by phosphorylation of Tyr 8 and Tyr 21 within the glycolytic enzyme binding site on band 3. This phosphorylation results in obstruction of enzyme binding, leading to G3PDH activation. Although not essential to the hypothesis, molecular modeling studies reveal that G3PDH interacts with band 3 like a "donut on a string" in a manner that is sterically prohibited by phosphorylation of band 3. The tyrosine kinase involved in band 3 phosphorylation is further demonstrated to be regulated by receptors located in the plasma membrane of the erythrocyte. Any agent which activates the tyrosine kinase is shown to coordinately activate red cell glycolysis. Conversely, any pharmaceutical which blocks tyrosine phosphorylation of band 3 also blocks stimulation of glucose metabolism. The change in profile of glycolytic intermediates resulting from stimulation of the kinase reveals a cross-over at the G3PDH reaction, confirming G3PDH as the site of this regulation. Thus, while steady state red cell metabolism may be regulated by conventional feedback inhibition, external modulation of the glycolytic flux is likely controlled by tyrosine kinase regulation of the inhibitory association of G3PDH with band 3. PMID- 2201290 TI - Recent advances in the biochemistry of favism. PMID- 2201288 TI - A common ancestor for mammalian 3 beta-hydroxysteroid dehydrogenase and plant dihydroflavonol reductase. PMID- 2201291 TI - Glucose-6-phosphate dehydrogenase from Plasmodium berghei: kinetic and electrophoretic characterization. AB - Evidence is given for the existence of a parasite-specific glucose-6-phosphate dehydrogenase in Plasmodium berghei by characterization of its kinetic and electrophoretic properties. After separating the parasites from infected RBC the G6PD was purified by affinity chromatography with 2'5'-ADP-Sepharose 4B. In cellulose acetate electrophoresis malarial G6PD significantly differs from the red cell enzyme. The subunits of the parasite-specific G6PD have a molecular weight of 55 kD in contrast to 59 kD of the RBC enzyme. G6PD from P. berghei shows no cross-reactivity with antibodies against G6PD from rat erythrocytes. The Km-value for G6P of malarial G6PD is increased by one order of magnitude compared with the host cell enzyme. PMID- 2201292 TI - Nucleotide status in erythrocytes of rats infected with Pl. berghei. AB - Nucleotide concentrations in erythrocytes of rats infected with Plasmodium berghei were measured by ion-pair reversed-phase HPLC. UTP and GTP levels were higher in highly infected red blood cells obtained after density separation. The infected red blood cells possess higher hypoxanthine, adenine, and adenosine levels. PMID- 2201293 TI - Application of immunological methods for the visualization of PK after IEF in ultrathin layers. AB - Immunological methods are recommended for protein visualization after IEF on account of their high sensitivity, good specificity and resolution. We used the indirect immunoassay with peroxidase- and 125I-labelled antibodies to investigate microheterogeneity of pyruvate kinase (PK) from human red blood cells and could show a PK pattern with more than 10 single bands. Different methods were tested as to their applicability for protein fixation and subsequent immunological visualization on the polyacrylamide gel. Beside Western blot, immunofixation and ethanolic fixation can be recommended as fixation techniques especially after isoelectric focusing in ultrathin gels. PMID- 2201294 TI - Genetic control of cell communication in C. elegans development. AB - Cell communication is crucial for many aspects of growth and differentiation during the development of the nematode Caenorhabditis elegans. Two genes, glp-1 and lin-12, mediate a number of known cell-cell interactions. Genetic and molecular analyses of these two genes lead to the conclusion that they are structurally and functionally related. We summarize these studies as well as those involving the identification of other genes that interact with glp-1 and/or lin-12. PMID- 2201296 TI - From gene to phenotype in Drosophila and other organisms. AB - The growing number of cloned eukaryotic genes lacking a defined or proven biological function poses a major challenge in 'reverse genetics'. A method is described here that permits efficient screening for new lesions in, or close to, genes corresponding to cloned DNA sequences of interest. The technique involves transposon mutagenesis, followed by screening of DNA isolated from a population of mutagenised individuals (or their progeny) for evidence that the population contains at least one individual in which transposon insertion has occurred at the target locus. Detection of rare individuals within the population is facilitated by the use of the polymerase chain reaction (PCR). Once recognised, specific individuals (or their progeny) are isolated from the population by a process of sib-selection. In cases where insertion of the transposon has occurred close to, but not within, the target locus, secondary events involving imprecise excision of the transposon will nonetheless allow the isolation of mutant individuals. Though the method was developed specifically for the transposon mutagenesis of Drosophila, extensions to other organisms and to other mutagenic strategies are feasible and some of the possibilities are discussed. PMID- 2201295 TI - Chromosome reproduction: units of DNA for segregation. AB - Evidence is summarized which indicates that the DNA loop anchoring proteins in chromosomes are effectively heterodimers that stack and are fastened into a bilaterally symmetrical array along the chromonemal axis. The evidence consists primarily of the observations made twenty five to thirty years ago on the pattern of sister chromatid exchanges and the way the DNA chains are sorted in the formation of diplochromosomes in cells that have undergone endoreduplication. The evidence indicates that each chain of DNA in the single duplex, which is assumed to run the length of a chromosome, is anchored to a bilaterally symmetrical axis of heterodimers that sort the two original chains among the four derived chromatids of each diplochromosome in a very precise way. These observations are considered in the context of investigations on the nature of scaffold proteins and the loop anchorage sequences, as well as the advances being made on the nature of DNA binding proteins and the roles of topoisomerase II. PMID- 2201298 TI - Antisense agents in pharmacology. PMID- 2201297 TI - Effect of hyperthyroidism and hypothyroidism on rat red blood cell insulin receptors and catecholamines: relationship with cellular ageing. AB - Insulin receptor activity and its relationship with catecholamines in rat young, middle aged and old red blood cells were investigated in experimental hypothyroidism and hyperthyroidism. In control animals, a loss of insulin receptor activity was found with cellular ageing and increased levels of norepinephrine, epinephrine and glycosylated hemoglobin. There was down regulation of insulin receptors together with alterations in membrane bound catecholamines in thyroid hormones imbalances. These results suggest that loss of insulin receptor in cellular ageing is probably part of a more generalised alteration and rat serves as an excellent model in defining the role of thyroid hormones in carbohydrate tolerance. PMID- 2201300 TI - In vivo evidence that insulin does not inhibit hepatic tryptophan pyrrolase activity in rats. AB - Previous reports have indicated that insulin administration triggers an early increase in plasma tryptophan (TRP) levels in fasted rats. Then, the present study was undertaken to investigate the putative role of liver tryptophan pyrrolase (TPO) in this short-term effect of insulin. In 24 hr fasted rats, doses of insulin that triggered an increase in plasma TRP levels (i.e., 2-3 I.U./kg, 1 hr) did not alter either holoenzyme or total enzyme activity. In another series of experiments, the administration of insulin (2 I.U./kg) to 24 hr fasted rats promoted biphasic time effects on plasma TRP levels and liver TPO activity. Thus, insulin initially triggered a rise in plasma TRP (without any change in liver TPO activity) and then increased liver TPO activity whilst plasma TRP returned toward control levels. In addition, hypercorticosteronemia was evidenced throughout the first phasis. Lastly, the influence of insulin administration (2 I.U./kg) on fasting-induced TPO induction was analysed. Whereas fasting increased liver TPO activity in a time-dependent manner, insulin administration (2 I.U./kg, 30 min) did not modify either plasma TRP or liver TPO activity. The data reported herein bring evidence that the effect of insulin administration on circulating TRP is not mediated by an inhibition of hepatic TPO. PMID- 2201299 TI - Kinetic modelling of the response of Plasmodium falciparum to chloroquine and its experimental testing in vitro. Implications for mechanism of action of and resistance to the drug. AB - The antimalarial mode of action of chloroquine (CQ) has been investigated in great detail in recent years, but the overall mechanism is still controversial. Instead of further probing the molecular aspects of partial reactions, a model based on the weak base properties of CQ and its delta pH-driven accumulation in acid parasite compartments has been devised, and the integrated response of the parasite to the drug under different experimental conditions has been assayed to verify the validity of the model. Factors such as inoculum size (parasitemia.hematocrit) and medium pH were altered using CQ-sensitive (FCC1) and -resistant (FCR3, VNS) isolates of Plasmodium falciparum. Experimental results were in full agreement with the predictions of the model, implying that therapeutic concentrations of CQ do not raise the pH of the food vacuole, i.e. that alkalinization of the acid parasite compartments is an insufficient explanation for the antimalarial activity of CQ, and that there is no need to invoke an active QC efflux pump to explain drug resistance. Calculations based on the model and the experimental data demonstrate that resistance to CQ is correlated with higher pH and/or higher resistance of the intracellular target to the drug concentration in the parasite food vacuole. The data also have implications for the design and interpretation of in vitro CQ inhibitory tests. PMID- 2201301 TI - Binding of a Bolton-Hunter substituted homostatine analog to affinity-immobilized human renin. AB - The binding of a Bolton-Hunter reagent substituted homostatine analog, SDZ 213 776, to human renin was investigated at pH 6.5 and 7.4. At both pH values, SDZ 213-776 bound to human renin in a reversible and saturable manner. The binding characteristics conformed to a one-site binding model. The dissociation constant Kd, obtained at equilibrium, was four-fold lower at pH 6.5 that at pH 7.4 (0.94 nM vs 3.7 nM). Under non-equilibrium conditions, only the association kinetic constant k+1 was affected by pH. The results of the binding assay at pH 6.5 correlated well with those obtained in enzymatic assay at the same pH. PMID- 2201302 TI - Potentiating effects of endothelin on platelet activation induced by epinephrine and ADP. PMID- 2201303 TI - [Is it necessary to search for dysplasia in Crohn's disease?]. PMID- 2201304 TI - [Sinus histiocytosis with massive lymphadenopathy. Destombes- Rosai-Dorfman syndrome]. PMID- 2201305 TI - New families of adhesion molecules play a vital role in platelet functions. AB - Adhesion molecules play a crucial part in cell-matrix and in cell-cell interactions. These interactions, which are essential to the body's defense processes, involve adhesion molecules belonging to different families: integrins, immunoglobulins and selectins. Integrins are expressed by a large number of tissues, whereas other adhesion molecule families are restricted to a small number of cell types. A recent symposium dealt with the recruitment of circulating platelets at specific sites, their adhesion to extracellular matrix components and their activation by agonists leading to aggregation or attachment to other cells. These events, supporting hemostasis and thrombosis, involve integrins, selectins and other adhesion molecules. This report focuses on newly reported integrins (GPIa, GPIc, GPIIa), selectins (GMP-140) and GPIIIb, previously known as 'minor' surface oriented platelet glycoproteins. Major membrane glycoproteins such as GPIIb-IIIa (an integrin) and GPIb, which also play a vital role in platelet functions, have been extensively reviewed elsewhere. PMID- 2201306 TI - Heat shock proteins: immunity and immunopathology. AB - Much interest has been generated in heat shock proteins (hsps) since they were implicated as dominant antigens of infectious microorganisms and suggested to have a role in the development of adjuvant arthritis (AA) in rats. Advances in the understanding of the role of hsps in immunity and immunopathology were recently discussed at a meeting held in Utrecht, as part of the European Community concerted action on immunopathogenesis and immunotherapy of chronic arthritis. PMID- 2201307 TI - What is the function of autoantibodies to cytokines? PMID- 2201308 TI - Age-related monoclonal gammapathies: clinical lessons from the aging C57BL mouse. AB - In this article the long-held notion that benign monoclonal gammapathy (BMG) is a premalignant stage in the development of multiple myeloma (MM) is attacked. Jiri Radl argues that clinical and experimental observations indicate that they are separate entities which may be distinguished in the laboratory and which should be managed in radically different ways. PMID- 2201309 TI - In search of the 'missing self': MHC molecules and NK cell recognition. AB - Natural killer (NK) cells can defend an organism against a variety of threats, probably using several different strategies to discriminate between normal and aberrant cells. According to the 'missing self' hypothesis, one function of NK cells is to recognize and eliminate cells that fail to express self major histocompatibility complex (MHC) class I molecules. In this article Hans-Gustaf Ljunggren and Klas Karre review in vivo studies with H-2-deficient targets that support this hypothesis. In vitro studies, some of which have given conflicting results, are interpreted within a multiple choice model for NK cell recognition. The authors derive testable predictions for how MHC class I molecules act in cases where they control a rate-limiting step in the NK cell-target interaction. PMID- 2201310 TI - Autocrine growth factors and tumourigenic transformation. AB - The development of tumours requires the simultaneous presence of a number of molecular perturbations. It is becoming increasingly clear that autocrine growth factor production, the topic of this review, is one such perturbation. Richard Lang and Antony Burgess summarize recent findings from a variety of in vitro and in vivo animal studies, and speculate on the possibilities for anti-growth factor therapy. PMID- 2201311 TI - The structure of the carboxyl terminus of the p21 protein. Structural relationship to the nucleotide-binding/transforming regions of the protein. AB - The carboxyl-terminal region of the ras oncogene-encoded p21 protein is critical to the protein's function, since membrane binding through the C-terminus is necessary for its cellular activity. X-ray crystal structures for truncated p21 proteins are available, but none of these include the C-terminal region of the protein (from residues 172-189). Using conformational energy analysis, we determined the preferred three-dimensional structures for this C-terminal octadecapeptide of the H-ras oncogene p21 protein and generated these structures onto the crystal structure of the remainder of the protein. The results indicate that, like other membrane-associated proteins, the membrane-binding C-terminus of p21 assumes a helical hairpin conformation. In several low-energy orientations, the C-terminal structure is in close proximity to other critical locales of p21. These include the central transforming region (around Gln 61) and the amino terminal transforming region (around Gly 12), indicating that extracellular signals can be transduced through the C-terminal helical hairpin to the effector regions of the protein. This finding is consistent with the results of recent genetic experiments. PMID- 2201312 TI - Localization and synthesis of an insulin-binding region on human insulin receptor. AB - Seven regions of the alpha subunit of human insulin receptor (HIR) were synthesized and examined for their ability to bind radioiodinated insulin. A peptide representing one of these regions (namely, residues alpha 655-670) exhibited a specific binding activity for insulin. In quantitative radiometric titrations, the binding curves of 125I-labeled insulin to adsorbents of peptide alpha 655-670 and of purified placental membrane were similar or superimposable. The binding of radioiodinated insulin to peptide or to membrane adsorbents was completely inhibited by unlabeled insulin, and the inhibition curves indicated that the peptide and the membrane on the adsorbents had similar affinities. Synthetic peptides that were shorter (peptide alpha 661-670) or longer (peptide alpha 651-670) than the region alpha 655-670 exhibited lower insulin-binding activity. It was concluded that an insulin-binding region in the HIR alpha subunit resides within residues alpha 655-670. The results do not rule out the possibility that other regions of the alpha subunit may also participate in binding of HIR to insulin, with the region described here forming a "face" within a larger binding site. PMID- 2201314 TI - Bibliography of the current world literature. PMID- 2201313 TI - An insulin-like compound consisting of the B-chain of bovine insulin and an A chain corresponding to a modified A- and the D-domains of human insulin-like growth factor I. AB - We report the synthesis and biological evaluation of a two-chain, disulfide linked, insulin-like compound consisting of the B-chain of bovine insulin and an A-chain corresponding to the A- and D- domains of human insulin-like growth factor-I (IGF-I) in which the A-domain amino-acid residues -Phe49-Arg50-Ser51 found in IGF-I have been replaced by -Ala-Gly-Val-, the homologous region of sheep insulin. The compound is indistinguishable from a previously reported compound whose A-chain corresponds to the A- and D-domains of IGF-I without the substitution, in assays for insulin-like activity as well as in assays for growth promoting activity. We conclude that these A-domain residues do not contribute significantly to the interaction of IGF-I with either insulin or IGF-I receptors. PMID- 2201315 TI - Application of flow cytometry to the study of HIV infection. PMID- 2201316 TI - Tat and Rev: positive regulators of HIV gene expression. PMID- 2201317 TI - Infection of human fibroblasts and osteoblast-like cells with HIV-1. AB - Primary human skin- and lung-derived fibroblast cell cultures and continuous human osteoblast-like and fibroblast-like cell lines were infected with different strains of HIV-1. Infection was measured at the single-cell level using the immunoperoxidase staining method to detect viral proteins. No cytopathic effects were observed in HIV-1-infected cell cultures. One continuous cell line (LC5), derived from embryonic lung, was readily infectable with HIV-1 and showed continuous production of infectious virus. Infection of LC5 cells could be blocked with anti-CD4 monoclonal antibodies. These findings indicate that fibroblasts of skin and lung, and osteogenic cells may be considered as potential target cells for HIV-1, thereby possibly contributing to the establishment of local HIV reservoirs. PMID- 2201318 TI - Immunogenicity and antigenicity of conserved peptides from the envelope of HIV-1 expressed at the surface of recombinant bacteria. AB - We expressed peptides from the HIV-1 envelope protein at the surface of Escherichia coli by genetic insertions into an exposed loop of the outer membrane protein LamB. Recombinant bacteria expressing eight peptides from gp110 (pep1 pep8), conserved between HIV-1 and HIV-2, were used as live immunogens in rabbits by the intravenous route. The eight constructions elicited anti-LamB antibodies, showing that the hybrid proteins were immunogenic. One of them, LamB-pep8, gave rise to antibodies able to react with gp160 and to neutralize HIV-1 in vitro. We also show that this type of recombinant E. coli can provide a convenient reagent to monitor and characterize specific antibodies. Recombinant clones were used to test sera of seropositive individuals, as well as to narrow down the monoclonal antibody 110-1 recognition site to a cluster of eight residues at the carboxy terminal end of gp110. PMID- 2201319 TI - Characterization of the African HIV-1 isolate CBL-4 (RUT) by partial sequence analysis and virus neutralization with peptide antibody and antisense phosphate methylated DNA. AB - The HIV-1 isolate CBL-4 (RUT), originating from Tanzania, was characterized using a comprehensive virus-typing system. This system included sequence analysis of the region coding for the neutralization domain in the third variable region (V3) of the external envelope and of the tat responsive (TAR) region after polymerase chain reaction (PCR) amplification of these sequences from cellular DNA in the CBL-4 (RUT) producer line. Based on independent cluster analysis of TAR and V3 sequences the CBL-4 (RUT) virus was positioned closest to the Z6 (and ELI) African virus family. The V3 amino acid sequence on the surface of the virus particle was confirmed by the inhibition of neutralization of CBL-4 (RUT) by a synthetic peptide derived from the nucleic acid sequence. Using antisense phosphate-methylated DNA covering the TAR loop region of LAV-1/HTLV-IIIB, inhibition of HTLV-IIIB and HTLV-IIIRF infection was seen, whereas no inhibition was observed for CBL-4 (RUT), indicating two or more mismatches in the TAR loop region, a characteristic shared with Z6 virus, but not with ELI. We propose a virus-typing system based on sequence analysis confirmed by virus neutralization with a peptide binding antibody and inhibition by antisense phosphate-methylated DNA to group viruses for laboratory use and vaccine design. PMID- 2201320 TI - Treatment with bovine hyperimmune colostrum of cryptosporidial diarrhea in AIDS patients. AB - Cryptosporidium parvum may cause severe, debilitating diarrhea in patients with AIDS. Recent anecdotal reports have suggested that hyperimmune bovine colostrum may be effective. We conducted a double-blind, controlled pilot study of hyperimmune bovine colostrum for diarrhea due to cryptosporidiosis in five AIDS patients. The patients were randomized to receive either hyperimmune or control colostrum by continuous nasogastric infusion for 10 days. All stools were collected, graded, and weighed, and the concentration of oocysts excreted was determined daily. One of the three patients treated with hyperimmune colostrum had a reduction in diarrhea and in the concentration of oocysts excreted. A second treated patient had a modest decrease in the concentration of oocysts excreted. Two patients who received control colostrum also had decreases in the volume of diarrhea but no change in the concentration of oocysts excreted. We conclude that hyperimmune colostrum with high titers of specific anti Cryptosporidium antibody could be effective in treating patients with cryptosporidiosis. However, more studies of cow colostral immunoglobulin need to be performed so that the efficacy of this treatment can be assessed more thoroughly. PMID- 2201321 TI - From theory to practice in the care and education of mentally retarded individuals. AB - Issues related to the care and education of mentally retarded individuals were examined from a historical perspective. Historical analysis shows that institutions and special education services spring from common, although not identical, societal and philosophical forces. The adequacy and implications of the normalization concept were discussed in relation to both deinstitutionalization and mainstreaming, with the conclusion that mental retardation workers must pay more attention to bettering the lives of retarded individuals and less to the "social address" at which interventions take place. Suggestions for the future care and education of retarded individuals were provided, and the proper role of science in the mental retardation field was discussed. PMID- 2201322 TI - [Significance of the captopril test in the diagnosis of primary hyperaldosteronism --apropos of 4 clinical cases]. AB - We describe four cases of primary hyperaldosteronism whose initial presentation was a moderate to severe hypertension. In three patients an adrenal adenoma was found; in another patient was due to unilateral adrenal hyperplasia. A good therapeutic response was achieved in all cases by unilateral adrenalectomy. The captopril test (Lyons version) proved useful to exclude essential hypertension and, may be, in distinguishing the new sub-types of primary hyperaldosteronism recently described. Indeed, only in the case of unilateral adrenal hyperplasia a fall in plasma aldosterone levels was observed. However, we feel that further investigation is needed to clarify this point. PMID- 2201323 TI - [Intervention cardiology in acute myocardial infarct]. AB - At the time when thrombolysis in acute myocardial infarction is well established, some controversy still exists about the exact role of coronary angioplasty in this setting. The rationale for a more aggressive intervention after thrombolysis lies in the fact that in a high proportion of the patients the infarct related artery remains occluded or there is a significant residual stenosis. In the latter case this would predispose to reocclusion and recurrent infarction and, by impeding coronary flow, it would limit the extent of myocardial salvage and the rate of myocardial healing. Angioplasty (PTCA) can be performed as an early procedure or late after thrombolysis. Early PTCA can be done as a primary procedure (Direct PTCA), following successful IC or IV thrombolysis (Immediate PTCA) or following unsuccessful thrombolysis (Rescue or salvage PTCA). Late PTCA can be used as a prophylactic (Deferred PTCA) selectively for recurrent angina or positive functional provocative test for ischemia. Direct PTCA has shown to be highly successful both in totally occluded arteries and in subtotal occlusions, with reduced incidence of access site, artery intimal and intramyocardial hemorrhage, but requires a 24-hour cardiac catheterization stand-by with high costs. It is certainly indicated in patients with contra indications to thrombolysis. Immediate PTCA has been evaluated in 3 large scale multicenter randomized controlled trials (TAMI, TIMI II A and ECSG) after IV rt-PA, and although with different design, they concluded that immediate PTCA offers no advantage over a deferred strategy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2201324 TI - [Silent ischemia after myocardial infarct]. AB - The Framingham study demonstrated that 25% of all episodes of acute myocardial infarction (AMI) do not present clinical symptoms, and are later recognized in a routine ECG. Silent ischaemia is frequently found after acute myocardial infarction, and has been identified in 25-60% of the patients according to the results of different studies and the different criteria employed for diagnosis. Silent ischaemia after AMI, as well as angina, is related with the presence and extent of severe coronary lesions located in the infarct related coronary artery or in other vessel not responsible for the acute episode of necrosis. The prognostic significance of silent ischaemia after AMI has not been well established. In some studies the painless ST segment depression during an exercise test soon after AMI presented the same prognostic value that the ST segment depression accompanied by angina, but in others the symptomatic episodes were a better predictor of major events and long term survival after the infarct. Several studies employing ambulatory ECG monitoring (Holter) also seem to indicate that the painless and transient episodes of ST segment depression identify a group of patients with worse prognosis, but in these studies the patients were selected, introducing a clear bias in the results of these investigations. Finally, asymptomatic transient perfusion defects in thallium studies clearly identify a group of high risk patients with a higher incidence of complications and higher mortality rate than the patients with negative thallium studies. The efficacy of anti-ischaemic drugs or myocardium revascularization procedures, including surgery, has not been studied in patients with silent ischaemia after acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2201325 TI - Genetic applications of alkaliphilic microorganisms. PMID- 2201326 TI - Breast cancer screening in women over age 50. A critical appraisal. AB - Breast cancer screening with mammography is strongly advocated by some and rejected by others. Discussions in the medical literature focus on the beneficial and unfavourable effects of breast cancer screening. Among the latter are the suggested excess mortality rate of screen-detected breast cancer patients, the high number of unnecessary biopsies, the possibility of overdiagnosis and subsequent unnecessary treatment, and the occurrence of interval breast cancer cases. It is concluded that screening can to a certain extent prevent women from dying of breast cancer but some negative effects are unavoidable. However, adequate training of the screening team can minimize the number of unnecessary biopsies and the occurrence of interval cancers. Research is needed to evaluate the natural course of so-called 'minimal' lesions, and to optimize screening tests. The search for new (imaging) techniques is needed to detect lobular cancers in dense breasts. PMID- 2201327 TI - Changes in atheroma volume estimated from digitized femoral arteriograms. AB - To evaluate the effects of treatment in patients with cardiovascular risk factors, valid and reproducible methods for assessing changes in atheroma volume are required. We postulated that these changes could be accurately estimated by repeat measurement of the lumen volume of the artery to be studied. With a computer-based technique, the lumen volume of a 20 cm segment of the femoral artery was measured in arteriograms from 107 patients with hypercholesterolemia. Films were digitized with use of a high-resolution scanner, cross-sectional areas were calculated with a slice thickness of 150 microns and the lumen volume was obtained by their integration. The validity of the method was demonstrated in model experiments. An automatic algorithm to correct for changes due to patient positioning was developed and validated in a model experiment. With repeat measurement 10 min and 11 to 13 months apart the coefficients of variation were 2.9 per cent (N = 107) and 6.1 per cent (N = 29), respectively. PMID- 2201328 TI - Ultrasonically guided percutaneous treatment of liver abscesses. AB - Twenty-two patients with liver abscesses demonstrated by ultrasonography (US) were treated over a nine-year period. The diagnosis was in all cases verified by puncture. The patients were treated by US-guided puncture or catheter drainage. Seventeen patients (77%) were cured without surgical drainage. Four patients were cured after subsequent surgical intervention. One patient died later of pancreatic carcinoma. There were no complications from the US-guided therapy. For the treatment of liver abscesses we recommend US-guided drainage as the first choice. Close collaboration between surgeon and radiologist is mandatory since some of these patients still need surgical treatment. PMID- 2201329 TI - Duplex Doppler ultrasonography for monitoring liver transplants. AB - The utility of duplex Doppler ultrasonography (US) for monitoring was evaluated after 19 liver transplantations. The assessment of the resistive index (RI) of the hepatic arteries showed no significant difference in the RI measured in grafts with stable function compared with grafts with ischemic damage, acute rejection, chronic rejection, or cytomegalovirus hepatitis. Nor was there any correlation between the levels of RI and the severity of acute rejection. In 2 out of 5 liver transplants in which hepatic artery pulsations were not identified with US, hepatic artery thrombosis was found at angiography. Although high echogenicity of the parenchyma was often observed during acute rejection episodes, it was not diagnostic for rejection. Fluid collections observed around the grafts resolved spontaneously. Thus, duplex Doppler US for monitoring liver transplants is especially useful for the diagnosis of hepatic artery thrombosis. It was not helpful for the diagnosis of acute or chronic rejection. PMID- 2201330 TI - Entrapped ovarian cyst. An unusual case of persistent abdominal pain. AB - Recurrent abdominal pain in the left fossa often mimicking attacks of subileus is described in a woman aged 48 with extensive adhesions caused by multiple surgical procedures. Repeated examinations with conventional abdominal radiography and barium meals were negative with regard to mechanical intestinal obstruction. A cystic lesion varying in size from 2 to 8 cm in diameter was seen adjacent to the left ovary on repeat US examinations and also on CT. Pain episodes were sometimes correlated to increasing size of the lesion which was finally thought to be either a peritoneal inclusion cyst (fluid trapped between pelvic adhesions) or, as was finally confirmed at surgery, a true ovarian cyst (corpus luteum cyst) similarly trapped. PMID- 2201331 TI - Diagnostic cyst puncture of multicystic kidney in neonates. AB - In the neonatal period it is important to differentiate hydronephrosis from cystic disease of the kidney, since treatment of these entities differ. Early surgery in hydronephrosis may be indicated to salvage kidney function. We studied a group of 29 infants with renal cysts or hydronephrosis. In 10 cases some doubt about diagnosis remained after thorough diagnostic imaging. These infants were examined using percutaneous puncture of the kidney to verify the suspected diagnosis of multicystic renal disease. The studies were performed using local anesthesia and sedation. Ultrasonography was used for puncture and contrast medium was injected during fluoroscopy. The cysts communicated in 7 out of 10 cases, and a true renal pelvis was never seen. Irregular tubular structures joining the cysts were identified in 7 cases and seem to be characteristic of the multicystic dysplastic kidney. One instance of the hydronephrotic type of multicystic kidney was found at surgery. Large size of the cysts can make diagnosis difficult. Percutaneous puncture was successful and gave the diagnosis in all cases. No complications ensued. PMID- 2201332 TI - Neonatal systemic candidiasis diagnosed by ultrasound. AB - The diagnosis of systemic candidiasis in ill high-risk neonates is often delayed as there are no specific clinical features and the significance of positive cultures for Candida species may be uncertain. Early diagnosis and treatment is essential to reduce mortality and may be aided by ultrasound examination of the commonly involved organs - the brain and kidneys. In this paper we describe 2 cases where the diagnosis was first raised following ultrasound examination, and review the spectrum of abnormalities seen on renal and cranial ultrasound examination. We emphasise the importance of using this imaging technique in the high-risk neonate in initiating earlier diagnosis and treatment, or in establishing the significance or otherwise of positive cultures. PMID- 2201333 TI - The significance of 'no significant difference'. AB - It is generally accepted that patients experience less discomfort with low osmolality contrast media (LOM) than with high osmolar media (HOM). Hard statistical facts from so called 'high quality' controlled trials, proving that more significant reactions such as vomiting, hives, urticaria or anaphylactic complications also are less common with LOM are, however, not readily available (3). One reason for this may be that most of the well designed controlled studies performed may have been tailored by the drug manufacturer for a specific purpose: to fulfil the format requirements for registration by the licensing governmental authorities. For this the sponsor, to save time, usually engages several medical centres, each only performing 15 to 60 studies (4). Materials of such a size are of course much too small to reveal any change in the frequency of a complication occurring with an incidence of only a few per cent or less. The absence of a statistically significant difference in such low incidences of complications does not justify any conclusion. The question then arises: how big a material would be needed to obtain a fair chance to statistically verify a clinically highly important decrease in the incidence of a complication from, for instance, 10 to 5 per cent? This paper deals with such questions. PMID- 2201334 TI - Assessment of knowledge of AIDS and beliefs about AIDS prevention among adolescents. AB - This report describes the development of measures of AIDS knowledge and beliefs about AIDS prevention for adolescents. Review of the literature, focus groups, pilot testing, and reviews by advisory councils assured that the process of developing the measures contributed to their validity. These measures were administered to three samples of adolescents at high risk for contracting AIDS: 43 runaway males, 43 runaway females, and 36 self-identified gay males. Both the knowledge and the beliefs instruments showed moderately high internal consistency and test-retest reliability and successfully avoided ceiling effects. Gay males demonstrated significantly greater knowledge of AIDS; however, there were few differences in beliefs among the groups. Knowledge of AIDS was significantly correlated with beliefs about AIDS prevention. The results suggest that these measures identify gaps in knowledge and beliefs among high-risk youth. PMID- 2201335 TI - Chromosomal translocations in lymphoid neoplasia: a reappraisal of the recombinase model. AB - Chromosomal translocations are common in tumors and are considered to represent one of the major classes of genetic alterations productive of the malignant phenotype. Although the molecular mechanisms leading to translocations are unknown, structural analysis of translocations in tumors derived from lymphocytes and their precursors has suggested the involvement of the lymphocyte recombinase, a normal cellular enzyme (or enzyme complex) that is essential for antigen receptor gene rearrangement. Recent observations of frequent recombinase-mediated interchromosomal exchanges between separate antigen receptor genes in normal lymphocyte precursors have provided clear examples of the ability of the recombinase to catalyze chromosomal translocation events, some of which may actually contribute to increased diversity of antigen receptor proteins. These findings have established that, even in the normal setting, the recombinase is not constrained to act only on gene segments linked in cis, but can also function in trans. Certain tumor-associated chromosomal translocations can be explained as subversions of this enzymatic capability. PMID- 2201336 TI - Glutathione S-transferases and drug resistance. AB - A remarkably diverse family of glutathione S-transferases (GSTs) has evolved in higher organisms. These intracellular enzymes catalyze the nucleophilic attack of glutathione on a variety of hydrophobic, electrophilic xenobiotics often resulting in conjugated or transformed metabolites that are less toxic and more easily excretable. Additionally, some GST isozymes may participate in the repair of oxidative damage to membrane lipids and DNA. Finally, GSTs are high capacity intracellular binding proteins which, independently of their enzymatic activities, may serve in the storage, transport, or sequestration of many hydrophobic compounds. These properties suggest that GSTs may function as important cellular defenses against the cytotoxic effects of carcinogenic and antineoplastic agents. Here we discuss recent evidence that bears upon this notion. PMID- 2201337 TI - Interleukin-2 and cancer therapy. AB - In summary, this meeting provided a useful overview of state-of-the-art research on IL-2. Significant gains have been made toward understanding the molecular biology and function of IL-2 and its receptors, but much remains to be learned about the intracellular signaling pathway by which IL-2 transduces its biological effects. Likewise, the nature of the lymphocyte subpopulation that responds to IL 2 requires detailed study, since it is now clear that T cells as well as LGLs can mediate non-MHC-restricted killing of tumor cells. Cell trafficking and effector cell activity within the tumor are other important issues to address. We also need to define the mechanism(s) by which IL-2-activated lymphoid cells mediate their antitumor effect in vivo; it is still far from clear whether these cells directly lyse the tumor cells, interrupt the tumor's vascular supply through endothelial cell damage, or produce other cytokines which then activate other cellular pathways. Preclinical data indicate that IL-2, with or without adoptive cellular therapy or in combination with other cytokines or drugs, can cause tumor regression. The success with animal model systems, however, has not always translated to success in the clinical setting-disappointingly, the majority of cancer patients still fail to respond to this treatment. It is hopeful the reasons for this will become apparent as more is learned about the molecular and cellular mechanisms involved in this "new" form of immunotherapy. PMID- 2201338 TI - Experimental models and biological mechanisms for tumor promotion. AB - Studies of skin tumor induction in the mouse have demonstrated that the process of carcinogenesis can be divided into two discrete stages: initiation and promotion. Research over the last twenty years has shown that this two-stage model generally applies to tumor induction in epithelial tissues. In many cases, the initiating event is the induction of a dominant mutation in a cellular proto oncogene. The promotion stage is complex, and represents a composite of events involving alteration in the expression of specific genes, proliferation of the initiated cell and its clonal descendants, and accumulation of additional genetic alterations. PMID- 2201339 TI - Levamisole as a therapeutic agent for colorectal carcinoma. AB - The prognosis of colon cancer patients found to have lymph node involvement at the time of primary surgical resection is guarded, with an overall 5-year survival rate of approximately 33%. The compound 5-fluorouracil (5-FU), an antimetabolite with some clinical activity in patients with metastatic colorectal cancer, has failed to produce a clinically meaningful impact when used as a single agent in the adjuvant setting. Recently, the results of a definitive intergroup trial (Moertel et al., N. Engl. J. Med. 322: 352-358, 1990) confirmed the results of a smaller trial that had suggested a therapeutic benefit from the combination of 5-FU and levamisole (Lev), an anthelminthic with immunomodulatory properties; these results have defined a new standard of care for patients with node-positive colon cancer. In this review, the rationale for using Lev as an adjuvant to 5-FU therapy in colon cancer, the immunologic effects of Lev in preclinical and clinical studies, and the results of clinical trials will be discussed. PMID- 2201340 TI - Cell-mediated killing: effector mechanisms and mediators. AB - Cytolytic T lymphocytes and natural killer cells appear to mediate cell killing by several different mechanisms. In one mechanism, a pore-forming protein, called perforin or cytolysin, is exocytosed by the effector cell and is inserted into the plasma membrane of the target cells, thereby collapsing its permeability barrier. Alternatively, the cytolytic cells activate a pathway of programmed cell death that causes specific fragmentation of target cell DNA. The physiological circumstances that determine which mechanism will be employed by the effector cells have not yet been fully determined. Recent experiments suggest that perforin is employed in situations in which there are high local concentrations of interleukin-2, such as cancer and acute viral infections, while a role for the programmed cell death pathway remains to be elucidated. PMID- 2201341 TI - The search for early genetic events in tumorigenesis: an amplification paradigm. PMID- 2201342 TI - Proliferation of anti-proliferation factors. PMID- 2201343 TI - Current status of cancer drug development: failure or limited success? AB - Murine leukemia models have been a major part of cancer drug screening strategies over the past 30 years. While these models have reliably identified agents active against human leukemias and lymphomas, they have been considerably less effective in identifying new agents for the treatment of common human solid tumors. This review considers the shortcomings of past approaches to cancer drug development, and describes new screening strategies designed to identify carcinoma-selective drugs. PMID- 2201344 TI - Integration of retroviral DNA into the genome of the infected cell. AB - Retroviruses replicate through an intermediate known as a provirus, a DNA copy of the viral genome that is covalently integrated into the host genome. The formation of the integrated provirus ensures the persistence of the viral genome in the infected cell and its transmission to daughter cells. Integration is thus central to the ability of retroviruses to make permanent genetic changes in the host cell through transfer of active oncogenes or through insertional activation of endogenous proto-oncogenes. Our current understanding of the integration reaction will be reviewed below. PMID- 2201345 TI - Growth control circuitry and the oncogene connection. PMID- 2201346 TI - Methods for antagonizing glutamate neurotoxicity. AB - Recent evidence suggests that glutamate-induced neuronal damage may contribute importantly to neuronal death in several neurological diseases, including cerebral hypoxia-ischemia. This review outlines a range of measures that might be used to protect neurons from such excitotoxic damage. The organizing thesis is a speculative consideration of glutamate neurotoxicity as a sequential three-stage process--induction, amplification, and expression--each perhaps specifically amenable to therapeutic interference. Overstimulation of glutamate receptors likely induces the intracellular accumulation of several substances, including Ca2+, Na+, inositol-1,4,5-trisphosphate, and diacylglycerol. Blockade of this induction might be accomplished most easily by antagonizing postsynaptic glutamate receptors, but also might be accomplished by reducing glutamate release from presynaptic terminals, or improving glutamate clearance from synaptic clefts. Following induction, several steps may importantly amplify the resultant rise in intracellular free Ca2+, and promote the spread of excessive excitation to other circuit neurons. Protective strategies operative at this level might include blockade of additional Ca2+ influx, blockade of Ca2+ release from intracellular stores, and interference with the mechanisms coupling glutamate receptor stimulation to lasting enhancements of excitatory synaptic efficacy. Following amplification, toxic levels of intracellular free Ca2+ might trigger destructive cascades bearing direct responsibility for resultant neuronal degeneration--the expression of excitotoxicity. The most important cascades to block may be those related to the activation of catabolic enzymes, and the generation of free radicals. Broad consideration of possible methods for antagonizing glutamate neurotoxicity may be needed to develop therapies with the greatest efficacy, and least adverse consequences for brain function. PMID- 2201347 TI - Platelet-activating factor--key mediator in neuroinjury? AB - A growing body of evidence supports the hypothesis that platelet-activating factor (PAF) may be a key mediator in neuroinjury. PAF, originally isolated from stimulated basophils, can be produced by a variety of cells, such as polymorphonuclear leukocytes (PMNLs), platelets, monocytes, macrophages, and endothelial cells and has been suggested as a mediator of inflammation, platelet and neutrophil activation, plasma extravasation, and anaphylactic shock. Enhanced phospholipid metabolism in the ischemic penumbral zone has been reported and provides opportunity for production of PAF. A possible involvement of this lipid mediator in processes associated with cerebral ischemia and neurotrauma has been suggested by an increasing number of reports. PAF exerts cytotoxic effects on neuronal cells, causes vasoconstriction, and increases the blood-brain barrier permeability. Beneficial effects of PAF antagonists have been shown in various models of cerebral ischemia: pre- as well as postischemic application of the PAF antagonist resulted in reduction of edema and improved neurological outcome and improved cerebral microcirculation. These effects were correlated with improved neuronal survival and reduced accumulation of PMNLs, supporting a link and positive feedback between PAF and PMNLs in these processes. Since PAF appears to be uniquely involved in various pathophysiological events, it may function as a key mediator in ischemic and traumatic neuroinjury. The current review summarizes the current understanding of the function and biochemistry of PAF with respect to CNS physiology and pathology. PMID- 2201348 TI - Cerebral autoregulation. AB - Autoregulation of blood flow denotes the intrinsic ability of an organ or a vascular bed to maintain a constant perfusion in the face of blood pressure changes. Alternatively, autoregulation can be defined in terms of vascular resistance changes or simply arteriolar caliber changes as blood pressure or perfusion pressure varies. While known in almost any vascular bed, autoregulation and its disturbance by disease has attracted particular attention in the cerebrovascular field. The basic mechanism of autoregulation of cerebral blood flow (CBF) is controversial. Most likely, the autoregulatory vessel caliber changes are mediated by an interplay between myogenic and metabolic mechanisms. Influence of perivascular nerves and most recently the vascular endothelium has also been the subject of intense investigation. CBF autoregulation typically operates between mean blood pressures of the order of 60 and 150 mm Hg. These limits are not entirely fixed but can be modulated by sympathetic nervous activity, the vascular renin-angiotensin system, and any factor (notably changes in arterial carbon dioxide tension) that decreases or increases CBF. Disease states of the brain may impair or abolish CBF autoregulation. Thus, autoregulation is lost in severe head injury or acute ischemic stroke, leaving surviving brain tissue unprotected against the potentially harmful effect of blood pressure changes. Likewise, autoregulation may be lost in the surroundings of a space-occupying brain lesion, be it a tumor or a hematoma. In many such disease states, autoregulation may be regained by hyperventilatory hypocapnia. Autoregulation may also be impaired in neonatal brain asphyxia and infections of the central nervous system, but appears to be intact in spreading depression and migraine, despite impairment of chemical and metabolic control of CBF. In chronic hypertension, the limits of autoregulation are shifted toward high blood pressure. Acute hypertensive encephalopathy, on the other hand, is thought to be due to autoregulatory failure at very high pressure. In long-term diabetes mellitus there may be chronic impairment of CBF autoregulation, probably due to diabetic microangiopathy. PMID- 2201349 TI - The paranasal sinuses. PMID- 2201350 TI - Advances in diagnostic and therapeutic imaging of the salivary glands. PMID- 2201351 TI - Orbital magnetic resonance imaging. PMID- 2201352 TI - The larynx and trachea. PMID- 2201353 TI - Imaging techniques in thyroid and parathyroid disease. PMID- 2201354 TI - Oropharynx and oral cavity. PMID- 2201356 TI - Neuroradiology. PMID- 2201355 TI - Dental radiology. PMID- 2201357 TI - Head and neck. PMID- 2201358 TI - Cerebral vascular diseases. PMID- 2201359 TI - Imaging of aging, degenerative, and demyelinating diseases. PMID- 2201360 TI - Recent developments in the imaging of neuraxis trauma. PMID- 2201361 TI - Imaging of intracranial neoplasms. PMID- 2201363 TI - Nondegenerative diseases of the spine. PMID- 2201362 TI - Degenerative disk disease. PMID- 2201364 TI - Advances in interventional radiology. PMID- 2201365 TI - Technical developments in magnetic resonance. PMID- 2201366 TI - Neuroimaging in various stages of human immunodeficiency virus infection. PMID- 2201367 TI - The petrous bone. PMID- 2201368 TI - Advances in radiologic diagnosis of nasopharyngeal tumors. PMID- 2201369 TI - Diffuse lung disease. PMID- 2201370 TI - Thoracic infections. PMID- 2201371 TI - Thoracic neoplasms. PMID- 2201372 TI - Pulmonary vascular diseases. PMID- 2201373 TI - Lung edema and adult respiratory distress syndrome. PMID- 2201374 TI - Interventional chest procedures and diaphragmatic hernias. PMID- 2201375 TI - New chest imaging methods for nodule detection and evaluation. PMID- 2201376 TI - The pharynx and esophagus. PMID- 2201377 TI - The stomach and duodenum. PMID- 2201378 TI - Small-bowel imaging. PMID- 2201379 TI - The colon. PMID- 2201380 TI - Imaging of the liver. PMID- 2201381 TI - Imaging of the spleen. PMID- 2201382 TI - Biliary tract. PMID- 2201383 TI - Motility studies. PMID- 2201384 TI - Radiology of the pancreas. PMID- 2201385 TI - Gastrointestinal angiography. PMID- 2201386 TI - Imaging of the gastrointestinal tract in the acquired immunodeficiency syndrome. PMID- 2201387 TI - Imaging of peritoneal pathology. PMID- 2201388 TI - Chest. PMID- 2201389 TI - Gastrointestinal tract. PMID- 2201390 TI - Spin-exchange NMR spectroscopy in studies of the kinetics of enzymes and membrane transport. AB - Spin-exchange NMR techniques enable the measurement of the rates of exchange of solutes between chemically or physically distinct sites in reactions taking place at chemical equilibrium. The time scale of the events that are able to be investigated lies in the neighbourhood of 1 s. The earliest studies in this area of NMR spectroscopy involved chemical reactions in vitro but the procedures have been adapted to the study of enzyme-catalysed reactions both in vitro and in vivo, and more recently to transmembrane exchange processes. The emphasis in this review is on the various types of spin-exchange experiments, the analysis of data derived from them, estimates of uncertainty in measured rate constants, and their shortcomings. Those methods given special attention are saturation transfer, two dimensional exchange spectroscopy (2D EXSY), the 'accordion' experiment and 'overdetermined' one-dimensional exchange spectroscopy. PMID- 2201391 TI - Malaria. Deaths from malaria acquired in Africa. PMID- 2201392 TI - Food safety. Egg-stuffed sea trout and salmonellae. PMID- 2201393 TI - World malaria situation 1988. Part I. Overview. PMID- 2201394 TI - World malaria situation 1988. Part II. Asia. PMID- 2201395 TI - Airport malaria. PMID- 2201396 TI - Failure of differentiation of the nuclear-perinuclear skeletal complex in the round-headed human spermatozoa. AB - Acrosomeless round-headed spermatozoa from three men were studied under electron microscopy and indirect immunofluorescene microscopy using the anti-calicin antibody that recognizes a basic protein of the sperm perinuclear theca (Longo et al., 1987). Electron microscopy revealed the existence of anomalies of the nuclear envelope, the nuclear matrix underlying the nuclear envelope, and the perinuclear layer. The absence of sperm labeling with the anti-calicin antibody confirmed that the formation of the perinuclear theca was impaired. Data obtained from both mature spermatozoa and ejaculated spermatids suggest that i) round headed sperm head anomalies result from a failure of differentiation of the sperm specific skeletal complex related to the nucleus, and ii) the acrosome spreading over the nucleus, the nuclear elongation and the post-acrosomal sheath formation are dependent on such nuclear-perinuclear differentiations. In contrast, chromatin condensation, cytokinesis and some events of the acrosomal shaping appear not to depend on those nuclear-related differentiations. The possible processes allowing the maintenance of the sperm head structures and their subsequent morphogenesis are discussed. PMID- 2201399 TI - Information sources for strategic planning by the nurse manager. PMID- 2201397 TI - Aromatase inhibition in advanced prostatic cancer: preliminary communication. AB - We report the results of the first use of a steroidal aromatase inhibitor, 4 hydroxyandrostenedione (4-OHA, CGP 32349), in the palliation of patients with advanced, hormone resistant, prostatic cancer. Twelve of 19 patients (63%), who had relapsed following castration and other therapies, gained significant pain relief following weekly intramuscular injections of 4-OHA. Five patients (31%) experienced a transient 'tumour flare', represented by an increase in bone pain soon after commencing treatment. The mechanism of action of 4-OHA in palliating patients with advanced prostatic cancer is obscure at present, but may represent an important new treatment modality which may lead to greater insight into prostatic biology. PMID- 2201398 TI - Lacking prognostic significance of beta 2-microglobulin, MHC class I and class II antigen expression in breast carcinomas. AB - To evaluate the impact of MHC antigen expression on the survival of patients with cancer, 77 human breast carcinomas were investigated for the expression of beta 2 microglobulin (beta 2m), HLA-A,B,C and HLA-DR. Thirty-one benign breast tumours were stained for comparison. The results for the carcinomas were related to the survival data of the cancer patients. The expression of beta 2m, HLA-A,B,C and HLA-DR was significantly lower in malignant tumours compared to the benign lesions. Whereas all benign tumours were positive for beta 2m and HLA-A,B,C and 28/31 positive for HLA-DR the following positivity rates were found in carcinomas: 74/77 for beta 2m, 57/77 for HLA-A,B,C and 10/77 for HLA-DR. The follow-up (median 45 months) of 66 cancer patients for overall survival and of 65 patients for disease-free survival revealed no influence of beta 2m, HLA-A,B,C or HLA-DR expression on the prognosis of this cancer. In conclusion, experimental data indicating the importance of MHC antigens in anti-tumour responses are not confirmed by the analysis of cancer patient survival data. PMID- 2201400 TI - Platelet adhesion. PMID- 2201401 TI - In vivo priming of human normal neutrophils by granulocyte-macrophage colony stimulating factor: effect on the production of platelet activating factor. AB - The effect of granulocyte-macrophage colony stimulating factor (GM-CSF) (recombinant, mammalian, glycosylated, Sandoz, Schering Plough; 4 micrograms/kg every 12 h for 3 d, s.c.) on platelet activating factor (PAF, 1-O-alkyl-2-acetyl sn glycero-3 phosphorylcholine) production from neutrophils was studied in five cancer patients with normal haemopoiesis. Peripheral blood counts, PAF production and lyso-PAF: acetyl transferase (EC 2.3.1.67) (AT) activity in neutrophils were evaluated before treatment, during treatment and 3 d after treatment had been discontinued. GM-CSF induced a three-fold increase in the number of circulating neutrophils. Neutrophils obtained during treatment produced about twice as much PAF than before treatment in response to a variety of stimuli (N-formyl-methionyl leucyl-phenylalanine, tumour necrosis factor-alpha, phagocytosis of baker's yeast spores opsonized with C3b). This increased PAF synthesis and release is concomitant with a 2-3-fold increase in AT activity. Moreover, lower concentrations of stimuli are sufficient to induce PAF synthesis from neutrophils obtained during GM-CSF treatment. Three days after treatment had been discontinued, stimulus induced PAF production had returned to baseline levels. Since GM-CSF induces a marked shift to the left in the Arneth score, the increased PAF release might have been due to the presence of younger granulocytes. This was, however, ruled out by experiments showing that normal neutrophils primed in vitro with GM-CSF produce more PAF when challenged with the same stimuli. The potential relevance of this effect of GM-CSF treatment lies on the crucial role of PAF in inflammatory reactions and its intervention in some immune reactions, including delayed hypersensitivity, and in endotoxic shock. Lastly, increased PAF production from neutrophils may explain some toxicities observed during treatment with high doses of GM-CSF. PMID- 2201402 TI - Colony stimulating activity in the serum of patients with multiple myeloma is enhanced by interleukin 3: a possible role for interleukin 3 after high dose melphalan and autologous bone marrow transplantation for multiple myeloma. AB - Sera from 36/37 multiple myeloma patients and 19/21 sera from patients with other solid or liquid tumours had granulocyte-macrophage colony stimulating activity (CSA) towards normal human donor bone marrow whereas 1/16 sera from normal donors had this activity. Unlike human rhGM-CSF and GM-CSF from 5637 (human bladder cell line) conditioned medium which is heat stable, CSA from serum is heat labile (56 degrees C/30 min). In multiple myeloma patients, CSA was detectable more than 2 years after treatment with 'high dose melphalan. Although multiple myeloma patients, at relapse, have sufficient CSA in their serum to produce maximal stimulation of GM-CFUc from normal donor bone marrow in vitro, their own GM population responds poorly. The results suggest that the failure of patients own bone marrow to respond to endogenous CSA may be due to damage to the stem cells of the marrow or the failure of precursor cells to respond to CSA. Addition of rhIL-3 to myelomatous serum increased the number of GM-CFUc from both normal and myelomatous bone marrow but did not stimulate the growth of MY-CFUc significantly. The results suggest that rhIL-3 may assist bone marrow recovery in multiple myeloma patients after intensive chemotherapy. PMID- 2201403 TI - Transfusion of ABO-mismatched platelets leads to early platelet refractoriness. AB - Forty-three consecutive patients previously unexposed to platelets and undergoing treatment for acute leukaemia or autografting for relapsed Hodgkin's lymphoma were randomized to receive transfused platelets of either their own ABO group (OG) or of a major mismatched group (MMG). The 26 evaluable patients were equally distributed between the two study groups. Nine of 13 (69%) MMG patients became refractory with a median onset at transfusion 7 (15 d), compared with only one of 13 (8%) OG patients (P = 0.001). Refractoriness was associated with the formation of high titre isoagglutinins, anti-HLA and platelet specific antibodies. In one patient refractoriness appeared to be due to high titre isoagglutinins alone. Six other patients developed an increase in isoagglutinin titre sufficient to adversely affect platelet increments. Patients receiving ABO-mismatched platelets had a higher incidence of anti-HLA antibodies (5 v. 1) and platelet specific antibodies (4 v. 1). ABO-mismatched platelets transfused prior to the onset of refractoriness resulted in increments similar to those achieved by ABO-matched platelets. The study demonstrates that ABO-mismatched platelets are as effective as matched platelets in patients with low titre isoagglutinins requiring only few transfusions. However, the greater incidence of early refractoriness induced in MMG patients indicates that ABO-mismatched platelets should not be given to patients with marrow failure requiring long-term support. PMID- 2201404 TI - Divalent metal ion binding to the CheY protein and its significance to phosphotransfer in bacterial chemotaxis. AB - Signal transduction in bacterial chemotaxis involves transfer of a phosphoryl group between the cytoplasmic proteins CheA and CheY. In addition to the established metal ion requirement for autophosphorylation of CheA, divalent magnesium ions are necessary for the transfer of phosphate from CheA to CheY. The work described here demonstrates via fluorescence studies that CheY contains a magnesium ion binding site. This site is a strong candidate for the metal ion site required to facilitate phosphotransfer from phospho-CheA to CheY. The diminished magnesium ion interaction with CheY mutant D13N and the lack of metal ion binding to D57N along with significant reduction in phosphotransfer to these two mutants are in direct contrast to the behavior of wild-type CheY. This supports the hypothesis that the acidic pocket formed by Asp13 and Asp57 is essential to metal binding and phosphotransfer activity. Metal ion is also required for the dephosphorylation reaction, raising the possibility that the phosphotransfer and hydrolysis reactions occur by a common metal-phosphoprotein transition-state intermediate. The highly conserved nature of the proposed metal ion binding site and site of phosphorylation within the large family of phosphorylated regulatory proteins that are homologous to CheY supports the hypothesis that all these proteins function by a similar catalytic mechanism. PMID- 2201405 TI - Substitution of arginine for histidine-47 in the coenzyme binding site of yeast alcohol dehydrogenase I. AB - Molecular modeling of alcohol dehydrogenase suggests that His-47 in the yeast enzyme (His-44 in the protein sequence, corresponding to Arg-47 in the horse liver enzyme) binds the pyrophosphate of the NAD coenzyme. His-47 in the Saccharomyces cerevisiae isoenzyme I was substituted with an arginine by a directed mutation. Steady-state kinetic results at pH 7.3 and 30 degrees C of the mutant and wild-type enzymes were consistent with an ordered Bi-Bi mechanism. The substitution decreased dissociation constants by 4-fold for NAD+ and 2-fold for NADH while turnover numbers were decreased by 4-fold for ethanol oxidation and 6 fold for acetaldehyde reduction. The magnitudes of these effects are smaller than those found for the same mutation in the human liver beta enzyme, suggesting that other amino acid residues in the active site modulate the effects of the substitution. The pH dependencies of dissociation constants and other kinetic constants were similar in the two yeast enzymes. Thus, it appears that His-47 is not solely responsible for a pK value near 7 that controls activity and coenzyme binding rates in the wild-type enzyme. The small substrate deuterium isotope effect above pH 7 and the single exponential phase of NADH production during the transient oxidation of ethanol by the Arg-47 enzyme suggest that the mutation makes an isomerization of the enzyme-NAD+ complex limiting for turnover with ethanol. PMID- 2201406 TI - Pre-steady-state kinetics of Escherichia coli aspartate aminotransferase catalyzed reactions and thermodynamic aspects of its substrate specificity. AB - The four half-transamination reactions [the pyridoxal form of Escherichia coli aspartate aminotransferase (AspAT) with aspartate or glutamate and the pyridoxamine form of the enzyme with oxalacetate or 2-oxoglutarate] were followed in a stopped-flow spectrometer by monitoring the absorbance change at either 333 or 358 nm. The reaction progress curves in all cases gave fits to a monophasic exponential process. Kinetic analyses of these reactions showed that each half reaction is composed of the following three processes: (1) the rapid binding of an amino acid substrate to the pyridoxal form of the enzyme; (2) the rapid binding of the corresponding keto acid to the pyridoxamine form of the enzyme; (3) the rate-determining interconversion between the two complexes. This mechanism was supported by the findings that the equilibrium constants for half- and overall-transamination reactions and the steady-state kinetic constants (Km and kcat) agreed well with the predicted values on the basis of the above mechanism using pre-steady-state kinetic parameters. The significant primary kinetic isotope effect observed in the reaction with deuterated amino acid suggests that the withdrawal of the alpha-proton of the substrates is rate determining. The pyridoxal form of E. coli AspAT reacted with a variety of amino acids as substrates. The Gibbs free energy difference between the transition state and the unbound state (unbound enzyme plus free substrate), as calculated from the pre-steady-state kinetic parameters, showed a linear relationship with the accessible surface area of amino acid substrate bearing an uncharged side chain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2201407 TI - Cloning and expression of the luxY gene from Vibrio fischeri strain Y-1 in Escherichia coli and complete amino acid sequence of the yellow fluorescent protein. AB - Vibrio fischeri strain Y-1 (ATCC 33715) emits light with a lambda max of 545 nm rather than the 485-nm emission typical of other strains of V. fischeri. The yellow emission is due to the interaction of the enzyme luciferase with a yellow fluorescent protein (YFP). On the basis of the N-terminal amino acid sequence of YFP, a mixed-sequence oligonucleotide probe was synthesized and used to isolate a 1.6-kbp HindIII fragment containing the first 208 bases of the gene that codes for YFP (luxY). Another synthetic oligonucleotide complementary to bases 167-184 of the YFP coding sequence was used to isolate a second (ca. 1.9 kbp) DNA fragment generated by digestion with both EcoRI and ClaI that contained the remainder of the luxY gene. The intact luxY gene, which encoded a 22,211-dalton polypeptide composed of 194 amino acid residues, was reconstructed from the two primary clones and is contained within a 765-bp SspI-XhoII fragment. Both strands of the entire luxY coding sequence were determined from the reconstructed gene, while the region surrounding the junction used in the reconstruction was also determined from the original partial clones. As with other genes that have been studied from V. fischeri, the luxY gene was unusually AT-rich. The sequence of luxY did not bear any apparent similarity to any of the sequences contained in the current GenBank database. Escherichia coli containing a plasmid with the luxY gene expresses a protein that reacts with antibody raised to authentic YFP. PMID- 2201408 TI - Effect of the distal residues on the vibrational modes of the Fe-CO bond in hemoglobin studied by protein engineering. AB - Using an Escherichia coli gene expression system, we have engineered human hemoglobin (Hb) mutants having the distal histidine (E7) and valine (E11) residues replaced by other amino acids. The interaction between the mutated distal residues and bound carbon monoxide has been studied by Soret-excited resonance Raman spectroscopy. The replacement of Val-E11 by Ala, Leu, Ile, and Met has no effect on the v(C-O), v(Fe-CO) stretching or delta(Fe-C-O) bending frequencies in both the alpha and beta subunits of Hb, although some of these mutations affect the CO affinity as much as 40-fold. The strain imposed on the protein by the binding of CO is not localized in the Fe-CO bond and is probably distributed among many bonds in the globin. The replacement of His-E7 by Val or Gly brings the stretching frequencies v(Fe-CO) and v(C-O) close to those of free heme complexes. In contrast, the substitution of His-E7 by Gln, which is flexible and polar, produces no effects on the resonance Raman spectrum of either alpha- or beta-globin. The replacement of His-E7 of beta-globin by Phe shows the same effect as replacement by Gly or Val. Therefore, the steric bulk of the distal residues is not the primary determinant of the Fe-CO ligand vibrational frequencies. The ability of both histidine and glutamine to alter the v(C-O), v(Fe-CO), or delta(Fe-C-O) frequencies may be attributed to the polar nature of their side chains which can interact with bound CO in a similar manner. PMID- 2201409 TI - An ultraviolet-inducible adenosine-adenosine cross-link reflects the catalytic structure of the Tetrahymena ribozyme. AB - When a shortened enzymatic version of the Tetrahymena self-splicing intervening sequence (IVS) RNA is placed under catalytic conditions and irradiated at 254 nm, a covalent cross-link forms with high efficiency. The position of the cross-link was mapped by using three independent methods: RNase H digestion, primer extension with reverse transcriptase, and partial hydrolysis of end-labeled RNA. The cross-link is chemically unusual in that it joins two adenosines, A57 and A95. Formation of this cross-link depends upon the identity and concentration of divalent cations present and upon heat-cool renaturation of the IVS in a manner that parallels conditions required for optimal catalytic activity. Furthermore, cross-linking requires the presence of sequences within the core structure, which is conserved among group I intervening sequences and necessary for catalytic activity. Together these correlations suggest that a common folded structure permits cross-linking and catalytic activity. The core can form this structure independent of the presence of P1 and elements at the 3' end of the IVS. The cross-linked RNA loses catalytic activity under destabilizing conditions, presumably due to disruption of the folded structure by the cross-link. One of the nucleotides participating in this cross-link is highly conserved (86%) within the secondary structure of group I intervening sequences. We conclude that A57 and A95 are precisely aligned in a catalytically active conformation of the RNA. A model is presented for the tertiary arrangement in the vicinity of the cross link. PMID- 2201410 TI - [Immobilization of myocardial tropomyosin]. AB - Immobilized granulated myocardial tropomyosin with magnetic properties of prolonged period of storage was obtained. Tropomyosin inclusion into granules emulsion polymerisation is 89.5%. The largest amount of protein is extracted from granules after 2-3 days, and later this process is slowed down. Studying temperature effect, the maximum protein output was also shown to be reached after 2-3 days and depends on the temperature. Processing of granules, containing tropomyosin, with a solution with high concentration of hydrogen ions, the same results were obtained as under the influence of temperature. The use of 3 mol potassium rodanide did not show the peak of protein washing out of granules. PMID- 2201411 TI - [Morphological changes caused by the dermonecrosis factor of the causative agents of cholera and various other intestinal infections]. AB - Intra- or subepithelial focal purulent inflammation with necrosis of exudating leucocytes during 1-2 days is developed in consequence of intradermal injection of the living cholera vibrios, cultured on membrane agar, or their supernatants. Sometimes coagulative necrosis of cover epithelium arises without preliminary purulent inflammation stage from the very beginning. Intradermal injection of living cholera vibrios leads to the development of coagulative necrotic foci in derma too. The vascular genesis of alterations mentioned above is supposed. PMID- 2201413 TI - Clinical trial of Myrcia uniflora and Bauhinia forficata leaf extracts in normal and diabetic patients. AB - 1. Myrcia uniflora and Bauhinia forficata were compared with placebo for their hypoglycemic effect in randomized cross-over double-blind studies in 2 groups of normal subjects (10 subjects each) and 2 groups of Type II diabetic patients (18 in the M. uniflora group and 16 in the B. forficata group). The protocol with each plant lasted 56 days. 2. After the ingestion of infusions of 3 g leaves/day of M. uniflora and B. forficata leaves, no acute or chronic effects on plasma glucose levels or glycated hemoglobin were found in either group. However, plasma insulin levels in the diabetic group were lower after M. uniflora than after placebo. 3. Among other clinical parameters tested, a statistically significant difference was found only in the alkaline phosphatase level after placebo compared with that after M. uniflora in the normal group. 4. There were no differences in any clinical parameters after the use of placebo or of B. forficata. 5. We conclude that infusions prepared from the leaves of M. uniflora or B. forficata have no hypoglycemic effect on normal subjects or Type II diabetic patients. PMID- 2201414 TI - The ethics of prophylactic trials of depression. PMID- 2201412 TI - How do normal and leukemic white blood cells egress from the bone marrow? Morphological facts and biochemical riddles. AB - Under normal circumstances only mature granulocytes and monocytes cross the bone marrow sinus wall, a trilaminar structure consisting of endothelial cells, a discontinuous basal membrane and an adventitial cell layer in order to get access to the blood circulation. In leukemia, however, immature white blood cells are able to traverse the barrier and to appear in the blood stream. Very little is known about the regulatory processes which govern the egress of white blood cells in healthy individuals and their malignant counterparts in patients with leukemia. The results of the few studies performed to address this question in animal and human leukemias all agree that the extent to which adventitial cells (fibroblasts) cover the endothelium in bone marrow is drastically reduced. This implies altered interactions between the leukemic and adventitial cells and their extracellular matrix. We propose here a model to explain the egress of normal cells and their leukemic counterparts. It is based upon our own experimental data and the general at present limited knowledge of the subject. It is hoped that this model will stimulate further research into this important aspect of leukemogenesis. PMID- 2201415 TI - Outcome in unipolar affective disorder after stereotactic tractotomy. PMID- 2201416 TI - Secularization and medicalization. AB - This paper examines Bryan Turner's view that medicine has replaced religion as the 'social guardian of morality.' It argues that Turner's failure to co-ordinate the theories of secularization and medicalization has prevented this hypothesis from being fully explored. A systematic and synthesized account of both medicalization and secularization is given, and used as the framework for a review of the history of Seventh-day Adventism-a sect that is both a product and an agent of the two processes. In conclusion it is suggested that medicalization may be conductive to sect development, and that secularization and medicalization are compatible models of social change. PMID- 2201417 TI - [The supply of drinking water: its past, present, future]. PMID- 2201419 TI - [Eulogy to Jude Turiaf (1904-1989)]. PMID- 2201418 TI - [Current role of functional and economic surgery in the treatment of cancer of the larynx]. AB - Unfortunately, cancer of the larynx is a frequent occurrence. In most cases, surgical treatment gives the best chances of survival. However, this type of surgery has always been dreaded and the loss of the voice has been the consequence most justly feared by patients and doctors alike. Our knowledge of anatomy and pathology has given us a better understanding of tumerous evolution in cancer of the larynx as well as the knowledge that the larynx is not a single block, but an organ composed of compartments with anatomically designated limits separating the segments. Therefore, in certain precise but numerous cases, segmentary surgery is possible. This segmentary surgery, which has proven effective from the oncological point of view, is at the same time functional, preserving the voice and normal respiration. A definition has been developed for partial laryngectomy, either vertical (laryngofissure and cordectomy, frontal lateral laryngectomy, hemiglottectomy) or horizontal (supraglottic laryngectomy with neck dissection) and their indications have been specified. Over the last twenty years, functional subtotal laryngectomy or reconstructive laryngectomy have appeared (J. J. Piquet, Labayle). These have proven their reliability on the functional level as well as on the level of the lesions. These techniques have transformed surgery for cancer of the larynx. Early diagnosis of cancer of the larynx is essential as is the medical procedure for determining the best adapted type of surgery for each patient to save his life and his voice. PMID- 2201420 TI - [Food toxicology: free residues, bound residues: respective toxicity]. AB - Two types of metabolites can be expected in food prepared from animals or plants treated with veterinary drugs or pesticides. The first types are represented by the drug itself and/or its primary metabolites as free or conjugated forms. Except for highly lipophilic compounds, these metabolites generally appear early and are noncumulative, since they are metabolized and eliminated rapidly. These substances may have toxic properties and may be metabolized to highly reactive electrophilic intermediates. We consider that they may be potentially toxic for consumers. The second type include covalently bound metabolites which appear later. Their presence can indicate a potential toxic effect in the target species, although these compounds have lost their chemical reactivity. They therefore probably represent low toxicity for consumers, especially considering their low bioavailability, which has been demonstrated for many veterinary drugs and pesticides. PMID- 2201421 TI - [Microbiology in Montpellier before Pasteur's era]. AB - Until Pasteur's discoveries, pathology included several verified but unexplained clinical data such as hospital infections, venereal and contagious diseases, and so on.... It is easy to imagine how important what the discovery of the germs life since it gave a logical explanation to a whole of coherent facts. Nevertheless this discovery was preceded by a long period during which the idea of transmissible germs slowly appeared. French and foreign Faculties are enrolled in this "prehistory" and there Montpellier played a significant part since microbiology had been directly admitted, during Pasteur's lifetime. In 1983, a research center named Buisson-Bertrand was created. In 1897 a chair was opened and one Institut Pasteur built in 1918. It was the first Institut Pasteur created in the provinces. PMID- 2201422 TI - [Eulogy to Georges Desbuquois (1901-1989)]. PMID- 2201423 TI - A chondrogenic cell line derived from a differentiating culture of AT805 teratocarcinoma cells. AB - A cell line, ATDC5, isolated from a differentiating culture of AT805 teratocarcinoma expressed a fibroblastic cell phenotype in a growing phase. With the addition of 10 micrograms/ml insulin to the medium, cells continued to grow even in a postconfluent phase, formed cartilage nodule-like cell aggregates, were stained with Alcian blue and produced cartilage-specific proteoglycan and type II collagen, typical marker molecules for chondrogenesis. Since ATDC5 cells also differentiated into unidentifiable pigmented cells, they are apparently composed of undetermined cells. ATDC5, therefore, provides a good model system with which to understand chondrogenic differentiation. PMID- 2201424 TI - Influence of electrolytes and non-electrolytes on growth and differentiation of Trypanosoma cruzi. AB - The influence of electrolytes and non-electrolytes, especially NaCl and sorbitol, on the metacyclogenesis and growth of Trypanosoma cruzi has been studied. The addition of 50 or 100 mEq/l NaCl to the culture media significantly increased the development of metacyclic forms. Other electrolytes and non-electrolytes had no effect on epimastigote-metacyclic differentiation. The growth rate was never modified to any extent. The influence of sodium concentration, osmotic pressure, among other factors, are discussed. Electrophoresis showed proteins bands which could be related either to the adaptation of T. cruzi to the new culture media or to the initiation of differentiation processes. PMID- 2201425 TI - A phase II randomized trial of megestrol acetate or dexamethasone in the treatment of hormonally refractory advanced carcinoma of the prostate. AB - The results of a randomized, multicenter, cooperative group trial evaluating hormonal therapy with either megestrol acetate or dexamethasone in advanced, hormonally refractory prostate cancer are reported. Three of 29 patients (approximately 10%) on the megestrol acetate arm experienced an objective response lasting 41, 84, and 202 days, respectively, whereas two of 29 patients (approximately 7%) on the dexamethasone arm achieved an objective response lasting 359 and 512 days, respectively. Twenty of 29 patients (approximately 69%) on the megestrol acetate arm had stable disease lasting for a median duration of 117 days, whereas 21 of 29 patients (72%) on the dexamethasone arm had stable disease for a median duration of 86 days. Median survival of all patients was 9 months from initiation of treatment. The median survival of all patients on the megestrol acetate arm was 268 days compared to 246 days for patients on the dexamethasone arm (P = 0.2). Neither dexamethasone nor megestrol acetate would seem to be of substantive value in altering the progression of advanced, hormonally refractory prostate cancer. PMID- 2201426 TI - Immunohistochemical study of melanocytic nevus and malignant melanoma with monoclonal antibodies against S-100 subunits. AB - Immunohistochemical localization of S-100 protein alpha and beta subunits in the cells of melanocytic nevi and malignant melanomas was studied by using monoclonal antibodies directed against each subunit. Although polyclonal anti-S-100 reactivities have been demonstrated uniformly in all nevus cells and melanoma cells, monoclonal anti-S-100 alpha and anti-S-100 beta reactivities were either absent or rarely found in ordinary junctional nevi or junctional nests of ordinary compound nevi. However, in the junctional nests of dysplastic junctional nevi and junctional components of dysplastic compound nevi, monoclonal anti-S-100 alpha reactivity become more frequent, whereas monoclonal anti-S-100 beta reactivity remains negative. In the superficial variety of melanomas such as superficial spreading melanoma and lentigo maligna melanoma, monoclonal anti-S 100 beta is nonreactive until vertical growth or invasiveness begins. Most nodular melanomas are positively stained with both monoclonal anti-S-100 alpha and anti-S-100 beta. It is suggested that monoclonal anti-S-100 alpha can be an indicator of active junctional nevus of melanocytic nevi and the reactivity with monoclonal anti-S-100 beta may be related to vertical progression of superficial spreading melanomas and lentigo maligna melanomas. PMID- 2201427 TI - Clinical and pathologic features of primary gastric rhabdomyosarcoma. AB - The authors report a case of a collision tumor composed of a primary gastric rhabdomyosarcoma intermingled with an adjacent infiltrating gastric adenocarcinoma. Only eight cases of gastric rhabdomyosarcoma have been reported previously and little information is recorded about the behavior of this tumor. Gastric rhabdomyosarcoma has several distinctive clinical features. It is a highly aggressive tumor (median survival, 2.5 months) occurring in both children and adults and frequently presents as metastatic disease to lung or cervical lymph node. The initial diagnosis is often difficult to establish, especially on biopsy material. In several instances, the correct diagnosis was established only at autopsy. The authors' patient was correctly diagnosed during life and received considerable benefit from cyclophosphamide, doxorubicin, and vincristine (CAV) therapy and survived for 26 months after diagnosis. Two of the previously reported eight cases of primary gastric rhabdomyosarcoma and this case have adjacent admixed glandular gastric adenocarcinomas. Since three of the nine known cases of primary gastric rhabdomyosarcoma have an adjacent admixed gastric adenocarcinoma, there appears to be a greater than chance association between these two tumors. PMID- 2201429 TI - Marijuana smoking and carcinoma of the tongue. Is there an association? AB - There is considerable theoretical evidence that marijuana should be carcinogenic. However, most reviews have found no direct evidence of chronic marijuana smoking causing lung cancer. Some recent reports implicate marijuana smoking as a cause of cancer of the upper aerodigestive tract, though most of the subjects were exposed to other, possibly confounding, etiologic factors, namely tobacco and alcohol. We report two cases of squamous cell carcinoma of the tongue in men who chronically smoked marijuana but had no other risk factors. The totality of cases may point to a predilection of marijuana smoke for carcinogenesis in the upper aerodigestive tract. This correlates with nonmalignant effects and may be related to a different method of smoking marijuana compared with tobacco. PMID- 2201428 TI - Melanin in a dentigerous cyst and associated adenomatoid odontogenic tumor. AB - The authors report on a case of dentigerous cyst associated with odontogenic adenomatoid tumor in an 8-year-old black Nigerian boy. Both the cyst and the tumor contained melanocytes and melanin-laden epithelial cells. To their knowledge this is the first reported case of melanotic follicular cyst and adenomatoid tumor. A review of the literature revealed that melanin is rarely found in odontogenic lesions. Since the neural crest influence on the development of odontogenic tissues is well established, the occurrence of melanocytes in these tissues is not surprising. A racial predisposition may be present; black patients predominated in the 15 reported cases of melanotic odontogenic lesions. PMID- 2201431 TI - Randomized comparison of doxorubicin and vindesine to doxorubicin for patients with metastatic soft-tissue sarcomas. AB - Two treatment regimens for metastatic soft-tissue sarcomas were compared in a randomized trial in the cooperative group setting. Histopathologic diagnosis was affirmed by pathology reference panel review in 72% of the 347 patients. In 21% of patients, the reference panel affirmed the diagnosis of soft-tissue sarcoma but disagreed as to type; 7% of patients were ineligible based upon cell type. Of 298 patients evaluable, measurable tumor regression (partial or complete response) occurred in 17% of patients to doxorubicin (70 mg/m2 intravenously) and 18% of patients to doxorubicin (70 mg/m2 intravenously) and vindesine (3 mg/m2 intravenously), each given every 3 weeks. No difference existed in complete response (4% for doxorubicin, 6% for doxorubicin and vindesine) or median survival (9.4 months for doxorubicin, 9.9 months for doxorubicin and vindesine). Overall, 60% of those patients on doxorubicin and vindesine and 46% on doxorubicin experienced a severe or worse toxicity of treatment (P = 0.01). With greater toxicity and lack of any gains in efficacy, the results do not support use of the combination of doxorubicin and vindesine for metastatic soft-tissue sarcomas. PMID- 2201430 TI - A clinical trial of biochemical modulation of 5-fluorouracil with N phosphonoacetyl-L-aspartate and thymidine in advanced gastric and anaplastic colorectal cancer. AB - A novel sequential administration schedule of PALA (N-phosphonoacetyl-L aspartate) and thymidine to enhance the cytotoxic effect of 5-fluorouracil (5FU) was tested in 36 patients with advanced gastric cancer and 21 patients with advanced poorly differentiated (anaplastic) colorectal cancer. The potency of 5FU was dramatically increased as indicated by the observation of dose-limiting leukopenia at less than one tenth the maximum tolerated dose of 5FU when given as a single agent by intravenous bolus technique. Twenty-five percent of gastric cancer patients and 33% of colorectal cancer patients experienced an objective tumor response, including three patients with complete response. However, response duration was brief (median, 6 months), and there were four treatment related fatalities due to severe and unpredictable leukopenia leading to sepsis. Survival was short with a median of 6 months for gastric cancer patients and 3 1/2 months for colorectal cancer patients. We conclude that therapeutic index of 5FU was not improved by the addition of PALA and thymidine in this patient population based on considerations of objective tumor response rate, patient survival, and toxicity. PMID- 2201432 TI - Management of malignant ovarian immature teratoma. Role of adriamycin. AB - Sixteen consecutive patients with pure ovarian immature teratoma have been treated at The Norwegian Radium Hospital between 1975 and 1987. The median age was 22 years. Thirteen patients had International Federation of Gynecology and Obstetrics (FIGO) Stage I disease and three had Stage III disease. None of the patients with Stage I disease had bilateral disease. In nine patients at least one ovary was conserved. Four cases were Grade 1, seven cases Grade 2, and five cases Grade 3. Adjuvant treatment consisted mainly of Adriamycin (Adria Laboratories, Columbus, OH). The chemotherapy regimen appeared to be highly effective because all patients are alive without evidence of disease (median follow-up, 85 months). No severe toxicity was observed. In patients without residual tumor after primary surgery, the authors prefer the adjuvant treatment with Adriamycin because this treatment has a lower toxicity and is as effective as combination chemotherapy (vincristine, dactinomycin, and cyclophosphamide or cisplatin, vinblastine and bleomycin). Some comments on initial surgery and second-look surgery are also given. PMID- 2201433 TI - Ewing's sarcoma metastatic at diagnosis. Results and comparisons of two intergroup Ewing's sarcoma studies. AB - Two Pediatric Intergroup Ewing's Sarcoma studies of patients with metastatic disease (IESS-MD) have used multimodal therapy consisting of intensive combination chemotherapy and radiation therapy (XRT) to areas of gross disease detected at the time of diagnosis. In IESS-MD-I, conducted from 1975 to 1977, 53 eligible patients were entered and received the chemotherapeutic agents vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cyclophosphamide, and dactinomycin with concomitant XRT (VACA + XRT). In IESS-MD II, conducted from 1980 to 1983, 69 eligible patients were entered and received 5 fluorouracil (5FU) in addition to the chemotherapeutic agents of IESS-MD-I; initial intensive chemotherapy was given and XRT was delayed until week 10 (VACA + 5FU, delayed XRT). The best response rate (complete and partial remissions combined) was 73% in IESS-MD-I and 70% in IESS-MD-II, so there was no statistical evidence of a difference in response rates (P = 0.62). The length of best response also was similar between studies (P = 0.79), with approximately 30% of the patients on both studies remaining in remission at 3 years. The percentage of patients surviving 5 years or more was 30 on the first study and 28 on the second study (P = 0.49). The major sites of relapse after a response were lung and bone, each occurring with nearly equal frequency. The age of the patient was related to both best response rate and survival: patients 10 years of age or younger had substantially higher response and survival rates than patients 11 years of age or older. The favorable prognosis for younger patients might be explained by a more favorable distribution of primary sites at diagnosis; 39% of patients 10 years of age or younger had rib primary sites, compared with only 16% for patients older than 10 years of age (P = 0.05). The frequency of life-threatening toxicity was substantially higher in IESS-MD-I (30%) than in IESS-MD-II (9%), but the frequency of fatal toxicity was similar (6% to 7%). Fatal complications included Adriamycin-induced cardiomyopathy, Pneumocystis carinii pneumonia, unspecified pneumonitis, and sepsis. The most common toxicity and complications were leukopenia and infections. PMID- 2201434 TI - Carcinosarcoma of the prostate in combination with adenocarcinoma of the prostate and adenocarcinoma of the seminal vesicles. A case report with immunocytochemical analysis and review of the literature. AB - A unique triad of a carcinosarcoma and an adenocarcinoma of the prostate as well as an adenocarcinoma of the seminal vesicles in a 67-year-old man is reported. The carcinosarcoma was investigated by immunohistochemical methods. The mesenchymal parts of the sarcoma showed chondromatous differentiation expressed by S-100 protein and vimentin. The undifferentiated epithelial elements of the carcinosarcoma reacted positively to the panepithelial antibody lu-5 and to carcinoembryonic antigen (CEA). The adenocarcinoma of the prostate stained with antibodies to panepithelial antigen (lu-5), prostatic acid phosphatase, prostate specific antigen and CEA, whereas the adenocarcinoma of the seminal vesicles reacted only to lu-5 and CEA. The literature is reviewed. PMID- 2201435 TI - Alpha-interferon structure and natural killer cell stimulatory activity. AB - Expression vectors for human alpha-interferon (Hu-IFN-alpha) J1, a site-specific mutant [Ser116]Hu-IFN-alpha J1, and Hu-IFN-alpha J/C or Hu-IFN-alpha C/J hybrids were constructed and expressed in Escherichia coli. These interferons and others were purified by immunoaffinity chromatography with a monoclonal antibody against human alpha-interferon. Their antiviral activity and ability to stimulate natural killer cell activity were determined in comparison to several other human interferons. These results provide some insight into structure-activity relationships for stimulating natural killer cells and confirm our previous conclusions that antiviral activity cannot be used to predict other activities for an individual IFN-alpha species. The observations suggest that the tertiary structure rather than any specific linear sequence of amino acids regulates the ability of the interferons to stimulate natural killer cell activity. PMID- 2201436 TI - Evaluation of cysteine adduct formation in rat hemoglobin by 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanone and related compounds. AB - The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) forms hemoglobin adducts in rats. Upon mild base treatment, 4-hydroxy-1-(3 pyridyl)-1-butanone (HPB) is released from this globin. HPB has been suggested as a dosimeter for exposure to and metabolic activation of tobacco-specific nitrosamines. The purpose of this study was 2-fold: (a) to determine whether cysteine adducts of NNK were precursors to HPB, and (b) to determine to what extent cysteine adducts accounted for the material bound to globin that is not released upon mild base hydrolysis. The chemistry of cysteine adduct formation was investigated by reacting N-acetyl-L-cysteine with three model compounds for pyridyloxobutylation by metabolically activated NNK: 4-(carbethoxynitrosamino)-1 (3-pyridyl)-1-butanone (1); 4-oxo-4-(3-pyridyl)-1-butylmethanesulfonate (2); and 4-iodo-1-(3-pyridyl)-1-butanone (3). Five adducts were isolated and characterized by their spectral properties and by independent syntheses: two diastereomers of N acetyl-S-[1-methyl-3-oxo-3-(3-pyridyl)propyl]-L-cysteine (7a,b), N-acetyl-S-[4 oxo-4-(3-pyridyl)-1-butyl]-L-cysteine (9), and two diastereomers of N-acetyl-S-(2 [2-(3-pyridyl)]-2,3,4,5-tetrahydrofuranyl)-L-cystein e (11a,b). Only 11a,b produced HPB upon mild base treatment; however, the chemistry of this adduct did not support its role as a major precursor to HPB released upon base treatment of globin. The formation of adducts in rat hemoglobin was then examined by reacting it with tritium-labeled 1 [( 5-3H]1) or tritium-labeled 4-oxo-4-(3-pyridyl)-1 butyl p-toluenesulfonate [( 5-3H]4). The results demonstrated that the amino acids corresponding to 7a,b were present in hemoglobin reacted with [5-3H]1, accounting for 72% of the bound tritium. Amino acids corresponding to 9 were not detected in this globin. In contrast, hemoglobin reacted with [5-3H]4 contained the amino acid corresponding to 9 (15% of bound tritium), but not those corresponding to 7a,b. These results indicated that the alpha, beta-unsaturated ketone, 1-(3-pyridyl)-2-buten-1-one (5), played a major role in the hemoglobin binding of 1, but not of 4. Cysteine adducts were not detected in globin isolated from rats treated with [5-3H]NNK. The results of this study provide insights into the mechanisms of cysteine adduct formation in vitro by pryidyloxobutylating agents and indicate that these adducts are not formed in NNK-treated rats. PMID- 2201437 TI - Aristolochic acid activates ras genes in rat tumors at deoxyadenosine residues. AB - Aristolochic acid I (AAI), a nitrophenanthrene derivative, is the major component of the carcinogenic plant extract aristolochic acid, which has been used as a medicine since antiquity. Long term oral administration of AAI to male Wistar rats induces multiple tumors, mainly in the forestomach, ear duct, and small intestine. The presence of activated transforming genes was investigated in various tumors of 18 AAI treated rats, namely in 14 squamous cell carcinomas of the forestomach, 7 squamous cell carcinomas of the ear duct, 8 tumors of the small intestine, 3 tumors of the pancreas, 1 adenocarcinoma of the kidney, 1 lymphoma, and 2 metastases in the lung and the pancreas. By utilizing the tumorigenicity assay and Southern blot analysis, we have detected an activated c Ha-ras gene in the DNAs of 5 of 5 squamous cell carcinomas of the forestomach. Direct sequencing of amplified material revealed an AT----TA transversion mutation at the second position of codon 61 of the c-Ha-ras gene (CAA to CTA) in all transfectants as well as in the 5 original rat tumors. Enzymatic amplification of ras sequences followed by selective oligonucleotide hybridization detected identical mutations in 93% (13 of 14) of forestomach tumors, in 100% (7 of 7) of ear duct tumors, and in the lung metastasis. Among those tumors tested, we had 4 cases in which the forestomach tumors and the ear duct tumors originated from the same rat, showing the same mutation in both tissues. Moreover, similar mutations were demonstrated at c-Ki-ras codon 61 in 1 of 7 ear duct tumors (CAA to CAT) and in 1 of 8 tumors of the small intestine (CAA to CTA) as well as at c-N-ras 61 (CAA to CTA) in a pancreatic metastasis. Additional transfection experiments of some tumors scoring negative for ras gene mutations in dot blot analyses revealed a CAA to CTA transversion at codon 61 of the c-Ha-ras gene in 1 forestomach tumor as well as at codon 61 of the c-N-ras in 1 hyperplasia of the pancreas and in 1 lymphoma. The apparent selectivity for mutations at adenine residues in AAI induced tumors is consistent with the identification of an N6-deoxyadenosine-AAI adduct formed by reaction of AAI with DNA in vitro, suggesting that carcinogen-deoxyadenosine adducts are the critical lesions in the tumor initiation by aristolochic acid. PMID- 2201438 TI - Selection for spontaneous metastasis after calcium phosphate-mediated transfer of DNA. AB - The ras oncogene has been shown to induce metastatic potential in a wide variety of cells. However, one cell line, C127, when transformed by ras (HC127), proved to be an exception in that the transformed cells gained the ability to form tumors in nude mice, but these tumors did not form spontaneous metastases. Because C127 cells do not metastasize after ras transfection, these cells can be used to identify other factors which contribute to the development of metastatic potential. Specifically, these cells can be used as recipients in DNA transfer experiments utilizing DNA from other cells in which H-ras has been used to induce the metastatic phenotype, thus allowing the search for genes in addition to ras itself which may be necessary for metastasis. A system utilizing genomic DNA transfer into C127 cells transformed by ras has been developed. These cells were used as the recipient for genomic DNA in cotransfection with pSV2neo followed by selection both in the experimental i.v. assay and in the spontaneous metastasis assay in nude mice. DNA from two lines with metastatic potential (both transformed by ras genes) gave rise to metastatic clones, whereas DNA from the recipient cells, HC127, NIH 3T3 cells, and two human tumor cell lines, CHP126 and A2058, failed to give rise to transfectants which could metastasize. The metastases after the first cycle were put into culture, and DNA was extracted from these cells and used in a second cycle of transfection. The capacity to metastasize was also transferred in the second cycle. Of seven metastatic clones examined, four showed no detectable rearrangements of the transfected v-H-ras gene, but in three of these clones, there were rearrangements of this gene, which was originally present in the recipient cell, HC127. This indicates that in a subset of the selected clones there may have been selection for rearrangements of the host genome rather than introduction of foreign DNA sequences, and that such effects must be considered in gene transfer experiments. It is also possible that the transfer of particular genomic DNAs are leading to genetic instability in these experiments. mRNA levels were compared in the metastatic variants and the parental cells; H-ras-specific RNA was raised from 4- to 22-fold in the metastatic cell lines, regardless of rearrangement of the v-H-ras gene. PMID- 2201439 TI - Malignant transformation of human fibroblasts by a transfected N-ras oncogene. AB - The only ras oncogene as yet identified in cells from human fibrosarcomas is N ras, but the relationship between N-ras oncogene expression and the malignant state of these cell lines is not known. To determine if expression of an N-ras oncogene causes human cells to become malignant, we transfected the N-ras oncogene from human leukemia cell line 8402, cloned into a high expression vector pSV N-ras, into MSU-1.1 cells, a nontumorigenic, infinite life span fibroblast cell strain with a normal morphology and a stable near-diploid karyotype. The transformants formed distinct foci composed of morphologically transformed cells. Cells from such foci expressed higher than normal levels of N-ras protein, exhibited growth factor independence, and formed large colonies in soft agar at a high frequency. Injection of progeny of these focus-derived cells s.c. into athymic mice resulted in progressively growing, invasive malignant tumors (round cell, spindle cell, or giant cell sarcomas) which reached a diameter of 6 mm in 3 to 4 weeks. Injection of focus-derived or tumor-derived cells i.v. resulted in tumors in various organs of the mice. The focus-derived cell strain tested, as well as the majority of the cells derived from the tumor it produced, exhibited the same near-diploid karyotype as the parental MSU-1.1 cells. Cells transfected with an N-ras oncogene that was expressed at a normal level formed only a single, indistinct focus, and cells from that focus were not malignant. PMID- 2201440 TI - Immunological and ultrastructural characterization of true histiocytic lymphoma in the northern pike, Esox lucius L. AB - An epidemic of a malignant neoplasm occurs in northern pike, Esox lucius L., from the Aland Islands of Finland. The neoplasm is morphologically similar to other pike hemic tumors reported in other areas of the world. Pike normal tissues showed evolutionary conservation with the mammalian intermediate filament proteins cytokeratin, desmin, vimentin, neurofilament protein, and glial fibrillary acidic protein; tumor cells are positive for vimentin, suggesting that the neoplasm is of mesenchymal origin. Hemic tissue mononuclear cells undergo polyclonal stimulation by the known mammalian T- and B-lymphocyte mitogens phytohemagglutinin P, concanavalin A, tuberculin-purified protein derivative, and lipopolysaccharide W; pike tumor cells are nonreactive. Pike normal hemic tissue mononuclear cells are variously positive for surface and cytoplasmic immunoglobulins, using rabbit anti-pike immunoglobulin M and cross-reactive mouse anti-carp immunoglobulin M antibodies; tumor cells, however, are not positive. The tumor cells were also diffusely stained with sodium fluoride-sensitive nonspecific esterase. The foregoing suggest that the neoplasm is not of B lymphocytic or plasmacytic derivation, while the T-lymphocytic as opposed to monocytic derivation cannot be excluded on the basis of marker studies. The ultrastructural studies, however, suggest a neoplasm of histiomonocytic derivation, while the absence of sinusoidal infiltration of tumor cells to head kidney, spleen, liver, or peripheral blood suggests that it is a piscine analogue of human true histiocytic lymphoma. Population dynamics studies indicate that the neoplasm affects primarily sexually mature males 5 to 6 yr of age, but does not at present appear to be a major factor affecting Aland pike populations. PMID- 2201441 TI - Epidemiology and immunovirology of human T-cell leukemia/lymphoma virus type I associated adult T-cell leukemia and chronic myelopathies as seen in France. AB - Seventeen patients with adult T-cell leukemia (ATL) and 21 with tropical spastic paraparesis/human T-cell leukemia/lymphoma virus type I (HTLV-I)-associated myelopathy (TSP/HAM) were observed during a 3-yr survey (1986-1988) in some hospitals in Paris, France. Most of them were black, originating from high-HTLV-I endemic areas (West Indies or Africa), but two cases of TSP/HAM occurred in French Caucasians. In one case, the patient acquired the virus from a transfusion during a cardiac transplantation. Most of the ATL cases were diagnosed as acute leukemia or lymphoma, with a proliferation of CD2+, CD3+, CD4+, CD8-, DR+, and CD25+ lymphoid cells. Only three cases were diagnosed as a smoldering ATL. All of the TSP/HAM cases exhibited a spastic paraparesis with a chronic and slow evolution and high HTLV-I antibody titers in serum and cerebrospinal fluid, with a high HTLV-I antibody index and specific HTLV-I immunoglobulin = oligoclonal bands. In TSP/HAM, a high percentage of DR-expressing cells (15 to 40%) was found, with a slightly elevated CD4/CD8 ratio. This was associated with the presence of 1 to 10% abnormally shaped nuclei in lymphoid cells and a polyclonal integration of HTLV-I proviruses in these peripheral blood mononuclear cells. On the contrary, a clonal integration was always found in the ATL malignant cells (leukemic, lymph node, and cutaneous infiltrate). Long-term interleukin 2 dependent T-cell lines (CD2+, CD3+, CD4+, and WT31+) with activated T-cell markers (CD25+ and DR+) producing HTLV-I were established from ATL and TSP/HAM peripheral blood mononuclear cells. PMID- 2201442 TI - Characterization of AIDS-associated tumors in Italy: report of 435 cases of an IVDA-based series. AB - The Italian Cooperative Group on AIDS-related tumors has collected 435 cases of HIV-associated tumors since December 1986. The following conclusions can be drawn from this IVDA-based series: (1) at least 15% of AIDS cases are associated with tumors; (2) the number of malignant lymphomas (high-grade non-Hodgkin's lymphoma [NHL], Hodgkin's disease [HD] is comparable to that of Kaposi's sarcoma (KS) (188 vs. 198); (3) KS among AIDS patients is less common than in countries where homosexual men are the main group affected by AIDS. However, KS also affects intravenous drug abusers (IVDA) almost exclusively males, with characteristics similar to those observed among homosexual men; (4) HD is associated with an aggressive course; (5) anal and oral primary tumors as well as oral and anal involvement of NHL are very rare; (6) testicular cancers occur in patients mainly with early HIV infection, without adversely affecting the dosage of radiotherapy and chemotherapy; (7) cervical cancer successfully treated with conization suggests that PAP test screening in young IVDA women is warranted; (8) lung cancer occurs in a young age group with rapid progression and death. PMID- 2201443 TI - Treatment of AIDS-associated malignancy. AB - Neoplasms associated with acquired immunodeficiency syndrome (AIDS) present unique therapeutic challenges. High-grade systemic lymphomas, although often responsive to standard chemotherapy, will require the addition of CSFs, infection prophylaxis, and antiretroviral drugs to overcome poor marrow reserves, short response durations, and opportunistic infections. Treatment of primary central nervous system (CNS) lymphomas is complicated by their frequent occurrence as a late complication in debilitated patients. AIDS-associated Kaposi's sarcoma (KS) is a unique neoplasm whose pathogenesis is only beginning to be understood. Although responsive to standard therapy (RT, chemotherapy), considerable attention has been focused on the therapeutic potential of BRMs. Interferon alpha (IFN-alpha), which combines antiviral, antiproliferative, and immunoregulatory activities, has significant anti-KS activity, particularly in symptom-free patients with mild immunosuppression. Preliminary data links IFN-induced regression of KS to its anti-HIV activity and supports a role for endogenous IFN alpha in the induction of refractoriness to IFN treatment. Recent data suggest synergistic anti-HIV and anti-KS activity for the combination of IFN-alpha and AZT. Additional study is needed to evaluate IFN effects on autocrine growth factors regulating the growth of KS. PMID- 2201444 TI - Local anesthesia failure in endodontic therapy: the acute inflammation factor. AB - The attainment of clinically acceptable local anesthesia is often problematic in the treatment of symptomatic pulpitis and symptomatic apical periodontitis. This article reviews the literature to identify the extent of this problem and to understand the organic components involved with this condition. Inflammation, infection, pH changes, alteration in nerve cell membranes, and anatomic variations are all possible causes for failure of local anesthesia during emergency endodontic therapy. PMID- 2201445 TI - Oral manifestations of HIV infection, Part II: Viral infections and neoplastic lesions. AB - The dental practitioner is in a unique position to detect the early signs of HIV infection that appear in the mouth. By identifying such lesions, the dentist can contribute to the early diagnosis and timely treatment of HIV-positive individuals. This article, the second of a two-part series, will review the clinical features, diagnosis, and treatment of the common viral infections and neoplastic lesions seen in association with HIV infection. PMID- 2201446 TI - Clinical observations of a titanium-alloy prefabricated post. AB - Clinical observations led to the development of this article in order that the dental profession may become cognizant of the ethereal radiographic appearance of titanium-alloy posts. PMID- 2201447 TI - Quantitative ultrasonic assessment of normal and ischaemic myocardium with an acoustic microscope: relationship to integrated backscatter. AB - PURPOSE OF INVESTIGATION: The aim was to study ultrasonic propagation properties of normal and ischaemic myocardium with a scanning laser acoustic microscope and to correlate these changes with ultrasonic backscatter. DESIGN: Myocardial ischaemia was produced by total occlusion of left anterior descending coronary artery in anaesthetised open chest dogs. Myocardium supplied by left circumflex coronary artery served as normal control. IBR5, an optimum weighted frequency average (4-6.8 MHz) of the squared envelope of diffraction corrected backscatter, was measured in vivo. Ultrasonic attenuation coefficient, an index of loss per unit distance, the propagation speed and heterogeneity index were measured from normal and ischaemic regions with a scanning laser acoustic microscope which operates at 100MHz in vitro. Myocardial water content of normal and ischaemic myocardium was also estimated. SUBJECTS: Were five anaesthetised mongrel dogs. RESULTS: Attenuation coefficient of 33.8(SD4.2) dB.mm-1 in the ischaemic tissue was lower than 63.8(17.2) dB.mm-1 in the normal tissue (p less than 0.01). Ultrasonic speed was lower in ischaemic than normal myocardium at 1584(25) v 1612(35) m.s-1 (p less than 0.05). Heterogeneity index of 11(7) m.s-1 in the ischaemic region was lower than 14(8) m.s-1 in the normal region (27% reduction, p less than 0.05). IBR5 and myocardial water content were higher in the ischaemic than the normal myocardium: -37.2(SEM1.8) dB v -46.6(0.6) dB, (p less than 0.01) and 80.9(0.0)% v 78(0.2)%, (p less than 0.05) respectively. CONCLUSION: Ultrasonic properties of the myocardium are significantly altered during acute ischaemia. PMID- 2201448 TI - Measurement of microvascular permeability to small solutes in man: limitations of the technique. AB - STUDY OBJECTIVE: The aim was to evaluate the limitation on the measurement of the clearance rate of a small solute, 99mTc DTPA, from intravascular to extravascular spaces imposed by diffusion of the solute back into blood during the period of measurement. DESIGN: The technique for measuring clearance also generates the regional plasma volume from which the solute is cleared. Back diffusion would result in an overestimation of this plasma volume. By applying the same technique to 99mTc labelled human serum albumin, which is not cleared over the period of measurement, a separate estimate of plasma volume can be made. SUBJECTS: The subjects were eight patients undergoing routine 99mTc DTPA renography for suspected outflow obstruction. MEASUREMENTS AND RESULTS: The ratio of plasma volumes based respectively on 99mTc DTPA and human serum albumin in a region of interest below the kidney was 1.04 (SD 0.09). The technique requires a region of interest over the cardiac blood pool from which the blood level of 99mTc DTPA is continuously monitored. When a correction was made for extravascular 99mTc DTPA in this cardiac region of interest, the ratio was unchanged: 0.97 (0.12). CONCLUSION: The technique is capable of measuring the clearance of 99mTc DTPA although, because of its small molecular size, the transfer rate is blood flow dependent, ie, its PS product is greater than its clearance. PMID- 2201449 TI - Cell-cell repulsion: clues from the growth cone? PMID- 2201450 TI - Protein degradation in the endoplasmic reticulum. PMID- 2201451 TI - TAR-independent activation of the HIV-1 LTR: evidence that tat requires specific regions of the promoter. AB - Replication of HIV-1 requires Tat, which stimulates gene expression through a target sequence, TAR. It is known that TAR is a Tat-responsive target. Since Tat increases transcriptional initiations from the HIV-1 LTR promoter, it is unclear mechanistically how Tat utilizes an RNA target. Here we show that TAR RNA is only one component of the Tat-responsive target. Efficient Tat trans-activation was observed only when TAR was present in conjunction with the HIV-1 LTR NF-kappa B/SP1 DNA sequences. TAR RNA outside of this context produced a suboptimal Tat response. We propose that TAR RNA serves an attachment function directing Tat to the LTR. A Tat protein engineered to interact with LTR DNA could trans-activate through a TAR-independent mechanism. This suggests that Tat also has a DNA target. PMID- 2201452 TI - Yeast heat shock factor contains separable transient and sustained response transcriptional activators. AB - The transcriptional induction of heat shock genes in eukaryotes is mediated by the heat shock transcription factor (HSF). In yeast, this induction appears to involve the phosphorylation of DNA-bound factor. I report here that HSF contains two distinct transcriptional activation regions. In response to a temperature upshift, an N-terminal region mediates transient increases in HSF activity and a C-terminal region is essential for sustained increases. These sustained and transient activities are regulated over different temperature ranges, and increases in both are associated with rises in the level of HSF phosphorylation. I propose that the two HSF activation regions are regulated independently in response to different stimuli. PMID- 2201453 TI - The yeast heat shock transcription factor contains a transcriptional activation domain whose activity is repressed under nonshock conditions. AB - Transcription of heat shock genes is induced by exposure of cells to elevated temperatures or other stress conditions. In yeast, it is thought that induction of transcription is mediated by conversion of a DNA-bound transcriptionally inactive form of the heat shock transcription factor (HSTF) to a DNA-bound transcriptionally active form. We have identified domains in HSTF involved in transcriptional activation and in repression of transcriptional activation at non shock temperatures. We present evidence that a temperature-regulated transcriptional activation domain exists in HSTF and that this domain is essential for survival of yeast cells at heat shock temperatures. We propose a model for temperature-regulated transcriptional activation by a derepression mechanism. PMID- 2201454 TI - [Hereditary angioneurotic edema. Management in pediatric surgery]. AB - Hereditary angioneurotic oedema is an autosomal dominant disorder associated with serum deficiency of functionally active C1 inhibitor protein (type 1) or normal serum level of functionally deficient C1-inhibitor (type 2). These biochemical abnormalities induce a complement activation which leads to episodic swelling of interstitial tissues usually of the abdominal viscera and of the upper airway with resultant asphyxia. Vasoactive peptides from the degradation of component C2 of the complement along with an activation of basophils by chemotactic substances from the degradation of C3 and C5 are the main mechanisms involved in vasodilatation and swelling. Attacks of angioneurotic oedema, sometimes fatal when involving the upper airway, can occur during any but usually during ear throat-nose, dental or facial surgery. This article describes the pathophysiology and the main features of the disease in children. It reviews the different treatments used to avoid attacks or to cure an attack of angio-oedema once it has begun, both during planed surgery and during emergency surgery. PMID- 2201455 TI - [Angioma of the umbilical cord. Apropos of a case]. AB - We report a case of umbilical cord angioma in a female newborn. Ultrasonographic antenatal diagnosis had suspected either an omphalocele or a tumor of the umbilical cord. A caesarean had been decided at term. Surgery was necessary to ligate the umbilical vessels. The cord was 37 cm long and 7 cm large in several places. It weighed 495 g. The interest of this case resides in its rarity. First description of this kind of tumor was made by Gerdes in 1864 and since, only 20 cases have been reported. Antenatal diagnosis difficulties in umbilical cord tumors are reviewed. Vitelin cyst, angioma, and teratoma represent the most common diagnosis which are histologically and clinically discussed. Associated malformations and complications of umbilical cord angioma are reviewed in the literature. PMID- 2201456 TI - Modulation by indomethacin of diethylnitrosamine-induced early changes in c-myc and c-ras expression and late incidence of preneoplastic lesions in rat liver. AB - We measured the levels of c-myc and c-ras expression before and after diethylnitrosamine (DENA) treatment in the liver of rats previously submitted to partial hepatectomy (PH), in the presence or absence of indomethacin (IMC), given at a dose that reduced by 75% the incidence of preneoplastic foci of altered hepatocytes scored 8 weeks after application of the carcinogen. The time-course evolution of c-myc response to PH was similar in IMC-treated and untreated rats (with a peak at 3-8 h at least as high in IMC-treated animals as in the hepatectomized reference group), whereas the overall c-ras response was significantly reduced by the IMC treatment, resulting in much lower c-ras expression at 18-24 h posthepatectomy. Treatment with DENA 24 h after PH did not significantly modify c-ras expression compared to partially hepatectomized controls. In contrast, DENA treatment resulted in a marked transient increase in c-myc expression that was at least as pronounced, if not the same, in the IMC treated animals. These results leave open the possibility that increased c-myc expression under DENA influence might play a role in foci induction but exclude that this might be sufficient. They are consistent with a role for c-ras expression in determining the susceptibility of hepatocytes towards the carcinogenic action of DENA. PMID- 2201457 TI - The development of a hypnotherapy service for children. AB - In September 1988, a Pain and Symptom Management Team was set up to offer hypnotherapy as part of the treatment of pain, discomfort and anxiety. Children are taught self-hypnotherapy skills. Of the first 51 cases referred, 36 were taken on for hypnotherapy and after two to three sessions 29 were rated as improved or much improved. An account is given of the approach of the team and of some of the possible pitfalls. PMID- 2201458 TI - A decade of development in immunoassay methodology. AB - Immunoassays are now very widely used in the clinical laboratory, either because no other type of assay system is feasible or because they are often the most effective and suitable of the possible analytical methods. The last decade has seen the development and refinement of many new immunoassay reagents and systems. The major trend has been away from liquid-phase assays involving radioisotopic labels, towards fast homogeneous or solid-phase assays capable of operation anywhere; and towards precise and reliable nonisotopic, automated or semi automated laboratory assays, often with detection limits measured in pico- or attomoles. The use of monoclonal antibodies is now widespread, and the methodologies of labels and of solid-phase components are much more sophisticated. New assay formulations, novel homogeneous systems, immunosensors, free-analyte assays, the importance of thorough validation and of interfering substances, and future trends are discussed. PMID- 2201459 TI - Analytical evaluation of a sensitive enzyme immunoassay for determinations of creatine kinase isoenzyme MB. AB - We have evaluated a new sensitive immunometric assay for the determination of creatine kinase (CK; EC 2.7.3.2) MB isoenzyme (NovoClone CK-MB), involving an enzyme label and two monoclonal antibodies directed against the B subunit and the M subunit, respectively. The anti-CK-B antibodies are bound to the solid phase. The assay was modified to be extremely sensitive and thus to measure the concentration range below and close to the cutoff value used for the diagnosis of myocardial infarction. A reference interval of 0-6 micrograms/L was found for 315 outpatients without myocardial diseases (132 men and 183 women); the overall median of the log-gaussian distribution was 1.91 micrograms/L (2.03 and 1.79 micrograms/L for men and women, respectively). Total and within-assay imprecision (CV) was less than 6% at the upper reference limit. The detection limit was 0.1 microgram/L. The assay provides a favorable signal-to-noise ratio: the calibrators 0.0, 2.0, and 30.0 micrograms/L give absorbances at 492 nm of 0.040, 0.140, and 1.600 A. respectively. We conclude that the assay provides biochemical identification of individuals with myocardial damage but without myocardial infarction. PMID- 2201460 TI - Consensus document: Hawk's Cay meeting on therapeutic drug monitoring of cyclosporine. AB - The optimal measurement method and clinical application of the therapeutic drug monitoring of cyclosporine remain uncertain. At a workshop held at Hawk's Cay, FL, from January 14 to January 17, 1990, 57 scientists presented their latest research findings, either in formal papers or as discussants. Lively debate and discussion followed presentation of extant and new methodologies for drug measurements as well as multicenter validation studies: applications of trough concentration monitoring in renal, hepatic, and bone-marrow transplants as well as in autoimmune disease; and alternative pharmacokinetic approaches to guide cyclosporine therapy. The process of inducing and maintaining optimal immunosuppression to facilitate graft success is a complex and often challenging task, requiring the combined expertise of multiple disciplines. Thus, the assembly of four of the groups essential to the transplant process--clinicians, laboratory scientists, the pharmaceutical company, and the manufacturers of cyclosporine measurement kits--provided a unique opportunity to evaluate therapeutic drug monitoring issues facing the transplant field. Here we present the major conclusions reached at the meeting, brief discussions of the study data on which they are based, and a summary of unresolved problems that will require further rigorous investigations. The Consensus Document was reviewed by all the workshop participants before we submitted this final manuscript. PMID- 2201461 TI - New solid-phase enzyme immunoassay of neuron-specific enolase in serum: effect of storage temperature, lipemia, icterus, and hemolysis. PMID- 2201462 TI - Continuous ex vivo and in vivo monitoring with chemical sensors. AB - The chemical species of principal clinical interest for continuous monitoring include oxygen, carbon dioxide, pH, potassium, and glucose. Although sensors exist for all of these analytes, relatively few continuous monitors are used for blood chemistries. Reviewing the available electrochemical and optical approaches along with the expected system performance requirements provides some insight into the reasons for this. In particular, the performance of sensor systems is significantly dependent on the environment in which they are used: transcutaneous, intravascular, intramuscular, etc. The future success and acceptance of "real-time" continuous monitoring of the critically ill patient probably does not require the development of new sensors for additional species. Rather, improvements in the stability of existing devices and protection of the sensor's chemistry from the environment are needed. Eventually, the development of new sensing technologies, e.g., near infrared spectroscopy, may lead to a completely noninvasive system capable of monitoring a broad spectrum of analytes. PMID- 2201463 TI - Through a glass darkly: the lung as a window to monitor oxygen consumption, energy metabolism, and severity of critical illness. AB - Medical diagnosis and therapeutic monitoring for critical illness require adaptation of laboratory analyses to the bedside. These are greatly helped by the modification of physiological and biochemical data-acquisition techniques to increase the number and accuracy of noninvasive variables that can be obtained from the patient. This paper addresses the choice of noninvasive measurements and is largely directed at the assessment of oxygen debt as a measure of the severity of ischemic and septic metabolic processes. Especially considered are those noninvasive measures of cardiorespiratory adequacy, key variables that need to be considered together with the metabolic function to adequately reflect the patient's state of accommodation to critical illness or injury. I describe a noninvasive sensor system linked to a computer work-station that functions in a pattern recognition mode to permit classification of patients as to the type and severity of their physiological adaptation. This system can serve as a sophisticated bedside monitor of the severity of the patient's condition, as a guide to therapy. PMID- 2201464 TI - Other aspects of metabolic monitoring in critically ill patients. AB - Cardiopulmonary monitoring remains the mainstay of intensive-care unit utilization of clinical chemistry resources. Its focus has been on the restoration and maintenance of oxygen transport. Metabolic monitoring, a relatively new area of application for clinical chemistry technology, focuses on cell metabolism and on cell-cell interaction as a mechanism of metabolic regulation. This latter application of monitoring is developing as a result of a better understanding of the pathogenesis of organ dysfunction and disease processes in intensive-care unit patients. Some of the clinical chemistry technologies used include analyses for amino acids and polyunsaturated fatty acids, measurement of cytokine concentration and activity, nutritional assessment and monitoring, more sensitive monitors of liver function, and assessment of altered immunity in critically ill patients. Use of these technologies, along with specific support measures, offers new avenues for decreasing infectious complications and reducing mortality and morbidity of patients in intensive-care units. PMID- 2201465 TI - How can new technology be introduced, evaluated, and financed in critical care? AB - We briefly review issues impacting the introduction, evaluation, and cost of technology in critical care, providing a clinician's perspective. Where appropriate, we note important distinctions between health-care systems in Canada and the United States--primarily the result of significant differences in the methods for funding health care in the two countries. Finally, we discuss what processes might be reasonably considered for evaluating technology in critical care and discuss the probability of various consequences that will significantly affect the care we provide our patients if critical-care practitioners, industry, and health planners fail to jointly undertake this responsibility. PMID- 2201467 TI - Analysis of mosaic states in amniotic fluid using the in-situ colony technique. AB - Appropriate counselling and clinical management of the pregnant woman with a mosaic amniotic fluid cell karyotype are difficult. The majority of the data on mosaicism and pseudomosaicism are derived from studies employing the flask technique for the analysis of amniotic fluid cell cultures. Since the majority of laboratories now utilize the in-situ technique, such data may not be relevant when analyzing results from the in-situ colony technique. We reviewed the incidence of mosaicism in 6339 amniotic fluid samples using the in-situ technique. Data are presented on the types of aberrations and clinical outcomes. A classification of mosaicism is presented that distinguishes mosaicism of clinical importance from that which is obviously of extrafetal origin or artifactual. This approach clarifies the significance of mosaic states detected by the in-situ colony technique and provides a rational foundation for genetic counselling and for planning clinical interventions. PMID- 2201466 TI - Retinitis pigmentosa: genetic mapping in X-linked and autosomal forms of the disease. AB - Retinitis pigmentosa (RP) is an hereditary degenerative disease of the retina and a major cause of visual impairment, prevalence estimates ranging from 1 in 3000 to 1 in 7000. The condition may segregate as an autosomal dominant, autosomal recessive or an X-linked recessive trait and it may also occur on a sporadic basis in up to 50% of cases. In the autosomal dominant form, close linkage to the DNA marker C17 (D3S47) was recently established in a large family of Irish origin displaying early-onset disease (McWilliam et al. 1989), multipoint analysis indicating the gene for rhodopsin as a likely candidate (Farrar et al. 1990). In that gene, a C----A transversion in codon 23, resulting in a proline----histidine substitution has now been identified in 17 of 148 unrelated ADRP patients in the United States (Dryja et al. 1990). This mutation is absent however in the original Irish pedigree (it is also absent in 21 other dominant Irish pedigrees, representing approximately 70% of the estimated ADRP population) indicating that another mutation, either in rhodopsin itself, or in a gene very closely linked to rhodopsin is responsible for the disease in that family. Analysis of other dominant pedigrees using the C17 and/or rhodopsin probes has indicated either tight linkage (Bhattacharya, Personal Communication), looser linkage, possibly indicative of a second locus on 3q (Olsson et al. 1990) or no linkage (Farrar et al. 1990, Blanton et al. 1990, Inglehearn et al. 1990). Extensive genetic heterogeneity thus exists in the autosomal dominant form of this disease, and in the light of these new observations, earlier tentative evidence for linkage of ADRP to the Rhesus locus on chromosome 1 will be re-evaluated. A locus for type II Usher syndrome (classical RP combined with congenital pedial deafness, and normal vestibular function) has now been established on the long arm of chromosome 1 (Kimberling et al. 1990). Type I Usher families, in which hearing loss is more profound and vestibular function absent, do not segregate with the same chromosome 1q markers, indicating the existence of another, as yet unlocated gene. In the X-linked form of the disease, two genes, XLRP2 and XLRP3, have been located on the proximal short arm of the X chromosome using a combination of physical and linkage mapping techniques, and there is some evidence to suggest a possible third locus more distally located.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2201468 TI - Pneumonitis in bone marrow transplant recipients results from a local immune response. AB - Eighteen recipients of allogeneic T cell-depleted bone marrow who developed 22 episodes of interstitial pneumonitis were investigated by bronchoalveolar lavage for the cause of pneumonitis. The cells obtained were examined using a panel of monoclonal antibodies with immunocytochemical techniques to identify lymphocyte subsets and the presence of surface molecules indicative of lymphocyte activation. The majority of patients had an excess of lymphocytes in lavage and most of these cells were positively stained with the McAb recognizing the CD8 antigen (suppressor/cytotoxic type T cells). Although the proportions of CD4+ (helper type) T cells were below normal, the absolute numbers were within normal limits, thus the CD4:CD8 ratio was consistently 1:1 or less. A large proportion of the CD8+ cells displayed HLA-DR molecules (RFDR1+), interleukin-2 (IL-2) receptors (CD25+) and high concentration of CD7 antigen (RFT2+). Further analysis revealed that most CD8+ cells were CD5+ (RFT1+) yet a large proportion (20-40%) were CD5-. A majority of CD8+ cells was also CD38+ (RFT10+) and Leu7+. No clear correlation between the emergence of a raised proportion of activated CD8+ cells and diagnosed cytomegalovirus infection was found. These results demonstrate, however, that cells with the phenotype of the resident T cells of the bronchial epithelium (CD8+CD5-) emerge to the air spaces and express activation markers. This raises the intriguing paradox of an aggressive local immune response occurring in an otherwise immunosuppressed group of patients. PMID- 2201469 TI - Rheumatoid factors and glomerulonephritis. AB - It is presently unknown whether rheumatoid factors have a pathogenic role in the development of various types of glomerulonephritis with immune deposits. Three isotypes of rheumatoid factors (RFs), which are autoantibodies to IgG, were measured using the solid-phase fluorescence immunoassay in sera from patients with diffuse proliferative lupus nephritis (DPLN), membranous lupus nephritis (MLN), IgA nephropathy (IgAN) and idiopathic membranous nephropathy (MN). RF activity of immunoglobulins deposited in the glomeruli from these patients was also studied by examining the binding of the FITC-conjugated human IgG and Fc portion of IgG to the glomeruli of renal biopsy specimens. IgG, IgA and IgM RFs were significantly increased in sera from patients with DPLN, and the increase was significantly lower in patients with MLN, IgAN and MN. Human IgG bound to immunoglobulin on the glomeruli only in DPLN, but not in MLN, IgAN or MN. The Fc portion of IgG was demonstrated to be involved in this reaction. It was suggested that RFs and IgG may play a major role in immune deposits on the glomeruli in DPLN and may be involved in the development of DPLN; however, this is not likely in MLN, IgAN or MN. PMID- 2201472 TI - Antineutrophil cytoplasm antibody (ANCA) associated vasculitis. AB - In 1982 we first reported the presence of antineutrophil cytoplasm antibodies (ANCA) in 8 patients with systemic vasculitis and segmental necrotizing glomerulonephritis. The results of long-term follow-up are described. Screening of 7,500 serum samples revealed positive ANCA in 9 additional patients with vasculitis. Eighty-eight other patients with vasculitis were ANCA negative, including 7 with microscopic polyarteritis nodosa (MPAN) and 8 with Wegener's granulomatosis (WG). Conversely, ANCA were never detected in the absence of vasculitis. Fourteen patients presenting with glomerulonephritis and ANCA were followed for a median of 6.3 years. Eleven patients had MPAN and 3 WG. Remissions were obtained with immunosuppressive therapy in all patients. Clinical relapse was associated with the reappearance of ANCA. Five-year survival was 89% and 5 year dialysis free survival was 77%. ANCA are specific markers for a sub-group of patients with vasculitis and are sensitive markers of disease activity. Glomerulonephritis associated with ANCA positive vasculitis has a favorable outcome with immunosuppressive therapy. PMID- 2201470 TI - Detection of transforming growth factor-beta in rheumatoid arthritis synovial tissue: lack of effect on spontaneous cytokine production in joint cell cultures. AB - The presence of transforming growth factor-beta (TGF-beta) in inflammatory joint disease was investigated. Synovial fluid from patients with rheumatoid arthritis (RA) and patients with other non-autoimmune inflammatory joint diseases contained high levels of both active and latent TGF-beta. Levels of active TGF-beta did not correlate with drug regimen in either patient group or with the recovery period in the individuals with non-RA joint disease. Freshly isolated synovial cells from individuals with RA were shown by Northern blotting to express the mRNA for TGF-beta 1 and to secrete latent TGF-beta protein which could be neutralized by antibodies to TGF-beta 1 and TGF-beta 2. Lipopolysaccharide-stimulated peripheral blood mononuclear cells from normal donors produced interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha) which was inhibited by pretreatment of these cells with recombinant TGF-beta. Cytokine production was not inhibited if the addition of TGF-beta was used after the inducing stimulus, suggesting that in activated cells cytokine production cannot be inhibited. This was confirmed by the observation that neither TGF-beta 1 or TGF-beta 2 inhibited spontaneous IL-1 or TNF-alpha production by rheumatoid synovial mononuclear cells in culture. These findings show that despite the presence of active TGF-beta in RA synovial joints and the spontaneous production of latent (potentially active) TGF-beta by RA cells in culture, additional TGF-beta did not inhibit ongoing cytokine synthesis in vitro. This suggests that TGF-beta may not inhibit cytokine production in the rheumatoid joint although it cannot be ruled out that in vivo TGF-beta already has an immunosuppressive effect which cannot be further increased in vitro by exogenous protein. PMID- 2201473 TI - HIV promoter activity in primary antigen-specific human T lymphocytes. PMID- 2201471 TI - Sequential measurement of the murine acute-phase protein serum amyloid P component (SAP) as an indicator of graft-versus-host disease following allogeneic bone marrow transplantation in mice. AB - Murine models of bone marrow transplantation (BMT) are used commonly for studies of the pathogenesis and treatment of graft-versus-host disease (GVHD). We report here that the sequential measurement of the mouse acute-phase protein SAP can be used to provide a sensitive, quantitative index of the severity of GVHD. Thirty mice underwent allogeneic, and a further 30 syngeneic BMT. GVHD was assessed in vivo by clinical appearances and weight change, and post mortem by histology and calculation of splenic indices. Blood was obtained twice/week for SAP measurement and blood culture. In all mice an initial rise in SAP levels due to irradiation was followed by a return to baseline. Thereafter in syngeneic marrow recipients levels remained low. In contrast, after allogeneic BMT SAP levels rose progressively as mice developed GVHD, reaching a peak of 135 micrograms/ml prior to death, from a nadir at day 20 of 15 micrograms/ml. Mice with high splenic indices and histological evidence of severe GVHD had significantly higher SAP levels than mice with mild GVHD (P = 0.0002). Elevation in SAP levels occurred independently of bacteraemia. We conclude that in murine BMT sequential measurement of SAP provides an objective means of assessing GVHD in vivo. PMID- 2201474 TI - Activity of synthetic peptides from the Tat protein of human immunodeficiency virus type 1. PMID- 2201475 TI - Blood vessels of the scalp and brain. PMID- 2201476 TI - BCG product released for therapy of urinary bladder cancer. PMID- 2201477 TI - Guidelines for malaria prevention revised to include primary role for mefloquine. PMID- 2201478 TI - Principles of analgesic use in the treatment of acute pain and chronic cancer pain, 2nd edition. American Pain Society. PMID- 2201480 TI - Psychiatric stigma in the classical and medieval period: a review of the literature. AB - It is widely appreciated that a social stigma surrounds psychiatric illness in contemporary society. Researchers have concentrated on the nature and consequences of psychiatric stigma. Although there exists much work on the social history of mental illness, stigma, per se, has not often been addressed in historical studies. This is a review of material bearing on the question of psychiatric stigma in classical antiquity and the medieval era of Western European societies. The cultural and social factors that contributed to the development of psychiatric stigma are reviewed and analyzed. PMID- 2201479 TI - Statistical methods for comparing dental diagnostic procedures. AB - In dental diagnosis, there are typically two or more clinical diagnostic procedures which may be used either independently or jointly to reach a conclusion regarding the presence of a particular disease in a patient. To determine which of these diagnostic procedures are more accurate, statistical methods may be applied to research data in which the true health status as well as the diagnosis provided by each clinical procedure are available on each observation. Results arising from this type of analysis can be of great interest to clinicians when the diagnostic procedures themselves are costly, painful, or even potentially harmful to the patient. Considered here is the special situation encountered in dental research in which each patient can have multiple concurrent cases of a certain disease such as caries, for then the statistical evaluation of diagnostic procedures is even further complicated. This report describes several statistical approaches for comparing the efficacy of diagnostic tests and illustrates their application on data from a study of diagnostic radiographs for dental caries. PMID- 2201481 TI - Clovoxamine in the treatment of depressed outpatients: a double-blind, parallel group comparison against amitriptyline and placebo. AB - In a double-blind, random-assignment, parallel-group trial, outpatients with major depression received either the new antidepressant clovoxamine, the tricyclic amitriptyline, or placebo for 6 weeks. By an "improvement" criterion of 50% or greater improvement in the Hamilton Depression Scale (HAM-D) total score, 88% of clovoxamine completers improved versus 75% with amitriptyline and 43% with placebo; however, due to small numbers, the differences failed to reach statistical significance. Diminished salivary flow was significantly greater with amitriptyline, as were complaints of dry mouth, somnolence, dizziness, and headache. Nausea and vomiting were more common in the clovoxamine-treated group. With amitriptyline, but not with clovoxamine, memory performance declined over a month. However, psychomotor performance was not affected. PMID- 2201482 TI - A review of clozapine: an antipsychotic for treatment-resistant schizophrenia. AB - This report reviews over 25 years of literature of the development, pharmacology, proposed mechanism of action, efficacy, adverse effects, and recommendations for use of clozapine. Clozapine, synthesized in 1960, is an efficacious antipsychotic that rarely causes extrapyramidal side effects. However, in the mid-1970s, it was associated with an increased incidence of agranulocytosis resulting in restrictions of use. Recent trials with treatment-resistant schizophrenic patients found clozapine to be superior to chlorpromazine and haloperidol, fortifying the potential contribution of this drug. This has generated optimism that clozapine will obtain Food and Drug Administration approval. Generally well tolerated, the 1% to 2% risk of agranulocytosis can be minimized with careful patient selection, white blood cell (WBC) count monitoring, and weighing of risks versus benefits for use beyond the relatively safe initial 4-week period. PMID- 2201483 TI - Schizophrenia and amyotrophic lateral sclerosis. AB - Schizophrenia and amyotrophic lateral sclerosis (ALS) are central nervous system (CNS) disorders of unknown etiology. The association of these two disorders has been infrequently reported in the literature, but is not a rare occurrence. Various neuromuscular abnormalities involving the alpha-motor neuron have been described in some patients with schizophrenia. This report reviews the literature on schizophrenia, psychosis, and ALS and describes two additional cases of schizophrenia associated with ALS. The possibility that the neuromuscular dysfunction in schizophrenia may predispose to ALS and provide an explanation for the association of these two disorders is discussed. Additional research data are needed to test this hypothesis. PMID- 2201484 TI - Perceptual asymmetries in the somatosensory system: a dichhaptic experiment and critical review of the literature from 1929 to 1986. AB - Dichhaptic matching of 3-D nonsense shapes was used to assess sex-specific differences in haptics. In an initial object exploration/description phase, strategy was manipulated with instructions to encode each object using either a visual image (which was drawn) or verbal description (tape recorded). These drawings or tape recordings were subsequently used on their own to identify each object. Attempts were made to maintain similarity between the verbal and spatial procedures, to avoid methodological biasing of hand superiorities (e.g., the same number of alternatives and the same presentation times were used). Differences in hand superiority did not, however, result. To obtain a broader perspective, a critical review table was compiled of the entire somatosensory asymmetry literature. Clear patterns emerged for all types of task when results potentially stemming from methodological biases and those based on only certain levels of samples were excluded. Somatosensory perceptual asymmetries are not robust, although hand superiorities are in the predicted direction when they do occur; nevertheless, we find little support for sex-specific asymmetries in these studies. Dichhaptic presentations lack the efficacy of other somatosensory (as well as tachistoscopic) tasks overall, possibly because of the time scale necessary for free haptic exploration. PMID- 2201485 TI - Evidence for retinal pathology following interruption of neural regulation of choroidal blood flow: Muller cells express GFAP following lesions of the nucleus of Edinger-Westphal in pigeons. AB - Choroidal blood flow in pigeons is regulated by the medial part of the nucleus of Edinger-Westphal (EW) via the ipsilateral ciliary ganglion. Interruption of this circuit by unilateral lesions of EW results in pathological modifications in the morphology of retinal photoreceptors in the ipsilateral eye in pigeons housed under 12hr light (400 lux)/12hr dark conditions. In the present study, we examined the effects of unilateral EW lesions on glial fibrillary acidic protein (GFAP) expression by retinal Muller cells in pigeons housed under the same lighting conditions. Since Muller cells in the retina of land vertebrates express increased GFAP during conditions of retinal pathology or stress (e.g. inflammation or hypoxia), this study would enable us to further evaluate the effects of disruption in the neural regulation of choroidal blood flow on the retina. We found that following EW lesions, retinal Muller cells expressed GFAP, with the precise intracellular location of the GFAP dependent on the amount of time elapsed following the lesion. One week after the EW lesions, GFAP labelling was restricted to the Muller cell endfeet in the nerve fiber layer and ganglion cell layer. By two-three weeks, the labelling had extended outward (or sclerad) into the portions of the Muller cells spanning the inner plexiform layer. Finally, by six weeks post-lesion, the entire extent of the Muller cell from the nerve fiber layer to the outer limiting membrane contained GFAP. No GFAP immunoreactivity in Muller cells was observed in the eyes contralateral to the EW lesions or in eyes in which the pupil had been fixed and dilated by lesions of the pretectal region. Our results suggest that the retina is in a state of physiological stress following interruption of the neural regulation of choroidal blood flow by EW lesions. Although the precise mechanisms by which altered choroidal blood flow regulation affects Muller cell GFAP production require elucidation, the results nonetheless highlight the importance of intact neural regulation of choroidal blood flow for retinal health. PMID- 2201487 TI - [Medico-dental anniversaries in 1989]. PMID- 2201486 TI - Surgical critical care. PMID- 2201488 TI - [Technics for preservation of occlusal parameters. 3. Reconstruction with loss of occlusal relations]. PMID- 2201489 TI - [Tokyo at the Pierre Fauchard Museum sale]. PMID- 2201490 TI - [Multicenter study of the use of pivampicilline in dentistry]. PMID- 2201491 TI - [History of dentistry in western painting]. PMID- 2201492 TI - [The history of dentistry through Western painting. 2. 17th and 18th centuries]. PMID- 2201493 TI - Link to fertility problems puts N2O under scrutiny. PMID- 2201494 TI - Dental anxiety: assessment, reduction, and increasing patient satisfaction. PMID- 2201495 TI - Fish oil-induced changes in apolipoproteins in IDDM subjects. AB - The aim of this study was to examine the effect of Max EPA (a commercially available fish oil preparation) on serum cholesterol lipoproteins and apolipoproteins in insulin-dependent diabetic (IDDM) men with dosages that were likely to be acceptable to patients. Twenty-two male IDDM patients aged 20-41 yr, 6 of whom had retinopathy, were recruited from the Royal Perth Hospital diabetic clinic. After screening, subjects were divided into three groups. Six of the subjects without retinopathy were randomly selected and allocated to a control group. The remaining 16 patients (10 without and 6 with retinopathy) received a fish oil supplement. All subjects were advised to maintain their usual dietary patterns. Sixteen patients, including the 6 with retinopathy, were instructed to take 15 Max EPA fish oil capsules/day with meals. Patients in the control group did not take Max EPA. Three weeks of Max EPA supplementation without other dietary modification led to a significant rise in total cholesterol (P less than 0.01), which could be accounted for by increases in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol. The increase in HDL cholesterol was explained by a 33% rise (P less than 0.001) in its HDL2 subclass. Changes in apolipoproteins were examined and showed that the level of apolipoprotein A-I increased after ingestion of fish oil and correlated significantly (P less than 0.05) with the rise in HDL cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2201497 TI - Effect of temporal distribution of calories on diurnal patterns of glucose levels and insulin secretion in NIDDM. AB - The effect of different temporal patterns of calorie intake on plasma glucose, serum insulin, and insulin secretion rates was examined in six patients with moderately well controlled non-insulin-dependent diabetes mellitus (NIDDM). Patients were studied on three separate occasions over 26 h. Total calories and food composition (50% carbohydrate, 15% protein, and 35% fat) were kept constant, but the pattern of calorie intake was varied. In study A (similar meal size), calories were distributed as 30, 40, and 30% at breakfast, lunch, and dinner, respectively. In study B (3 snacks, 3 meals), each subject ate three meals of 20, 20, and 30% of calories for breakfast, lunch, and dinner, respectively, and three snacks, each comprising 10% of calories, presented 2.5 h after the meal. In study C (large dinner), 10% of calories were consumed at breakfast, 20% at lunch, and 70% at dinner. Glucose, insulin, and C-peptide concentrations were measured at 15 to 30-min intervals. Insulin secretion rates were calculated from C-peptide levels with individually derived C-peptide clearance parameters. The different eating patterns were associated with only modest differences in overall levels of glucose and insulin secretion. Daytime insulin secretion was lowest when most of the daily calorie intake occurred in the form of a large dinner. Overnight levels of glucose and insulin secretion rates did not differ for the three eating patterns, and the morning glucose levels were also unaffected by the pattern of calorie intake on the previous day. A morning rise of glucose of greater than 0.28 mM occurred consistently only when dinner was of moderate size (30% of total calories).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2201496 TI - Metabolic response to oral challenge of hydrogenated starch hydrolysate versus glucose in diabetes. AB - Our objective was to determine whether 1) hydrogenated starch hydrolysates (HSHs), bulking/sweetening agents used in hard candies, produce a diminished postmeal glycemic response relative to glucose in individuals with and without diabetes and 2) any diminished glycemia is secondary to altered carbohydrate absorption. This study followed a randomized double-blind crossover design and was performed in 12 individuals with diabetes (6 non-insulin dependent, 6 insulin dependent) and 6 nondiabetic individuals. Each group consisted of 3 men and 3 women, none with known neuropathy. After an overnight fast, each subject was challenged with 50 g of glucose, HSH 5875 (7% sorbitol/60% maltitol), and HSH 6075 (14% sorbitol/78% hydrogenated maltooligosaccharides)/1.73 m2 of body surface area in random order on 3 successive days. Individuals with diabetes were maintained on continuous subcutaneous insulin infusion throughout the study to achieve prechallenge glucose levels between 4.5 and 6.7 mM. For all groups, the order of plasma glucose responses over 5 h postchallenge was glucose greater than HSH 6075 greater than HSH 5875, P less than 0.001 (glucose vs. HSH). Pooled data for all groups for areas under the curve confirmed that HSH 6075 resulted in greater glycemia than HSH 5875 (P less than 0.05). This was reflected in the order of C-peptide responses seen in the nondiabetic and non-insulin-dependent groups (glucose greater than HSH 6075 greater than HSH 5875, P less than 0.001). Breath H2 after glucose was low, whereas HSH 5875 greater than HSH 6075 (P = 0.003). Gastric distress was noticed with all products.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2201498 TI - Autonomic influence on pregnancy outcome in IDDM. AB - We evaluated the autonomic influence on pregnancy outcome with prospective study of 100 consecutive pregnancies in women with insulin-dependent diabetes mellitus (IDDM). Tests of cardiovascular autonomic nervous function were performed at the beginning of each pregnancy, and two groups were formed. Group 1 was comprised of 23 pregnancies with autonomic dysfunction, and group 2 was comprised of 77 pregnancies with no abnormalities in cardiovascular tests. Elective abortion was later induced for medical reasons in two cases in group 1, and these women were excluded from the study. The groups were comparable with respect to age, duration of diabetes, and presence of nephropathy. Both groups also achieved comparable glycemic control during pregnancy. There were no significant differences between groups 1 and 2 in any specific pregnancy complication (spontaneous abortions, 5 vs. 3%; perinatal mortality, 10 vs. 1%; congenital malformations, 10 vs. 4%; respiratory distress syndrome, 5 vs. 8%; preeclampsia, 20 vs. 10%; maternal ketoacidosis, 4 vs. 0%; and maternal hypoglycemic accidents, 10 vs. 4%, respectively), but the frequency of pregnancies with at least one of the above complications was greater in group 1 (52 vs. 23%, P = 0.01). Stepwise logistic regression analysis showed the association between autonomic dysfunction and pregnancy outcome to be independent of high initial glycosylated hemoglobin levels, long duration of diabetes, and nephropathy. Maternal autonomic dysfunction seems to be associated with an increased frequency of overall pregnancy complications but does not significantly interfere with the achievement of tight metabolic control during pregnancy. PMID- 2201499 TI - Predicting type I diabetes. AB - Currently, there are three markers that are being studied with the potential to give a high positive predictive value for the development of type I diabetes (insulin-dependent diabetes caused by autoimmune beta-cell destruction) and that can be utilized to predict the disease in susceptible relatives: 1) high-titer cytoplasmic islet cell antibodies, 2) insulin autoantibodies detected with fluid phase radiobinding assays, and 3) first-phase insulin release after intravenous glucose less than 1st percentile. With the combination of these assays, it seems to be possible to identify first-degree relatives with a high probability of developing type I diabetes within a limited time span (i.e., less than 10 yr). The ability to predict type I diabetes with selected assays will allow trials for prevention of diabetes and trials to assess whether prediction will decrease morbidity and mortality at onset of diabetes. PMID- 2201501 TI - Exercise and NIDDM. PMID- 2201500 TI - Cyclosporin therapy for prevention and cure of IDDM. Epidemiological perspective of benefits and risks. AB - Cyclosporin and other immunosuppressive agents have been proposed as a preventive treatment against the development of insulin-dependent diabetes mellitus (IDDM) in relatives at increased risk for the disease, based on the understanding that its etiology is an ongoing process of autoimmune beta-cell destruction. We used an epidemiological approach to evaluate several recent trials of cyclosporin in newly diagnosed IDDM patients to determine the degree of benefit that is to be expected. We assessed these and other studies to estimate the potential adverse effects of such treatment, were it to be used in the future, either in newly diagnosed subjects or healthy high-risk relatives. Standard sample-size calculations were used to quantify the number of study subjects necessary to allow adequate statistical power to test the positive and negative effects of a future treatment (alpha = 0.05, beta = 0.20). The estimates were based on the data available from published studies of cyclosporin treatment. The importance of conducting an adequate trial of such a therapy, both from an ethical and a practical viewpoint, is discussed. Five small immunosuppression trials were evaluated. Remission rates in treated subjects exceeded those in control subjects by 15-59%. Variability in defining remission may account for the differences in rates across the studies. Estimates of the major beneficial and adverse effects of cyclosporin were derived from these trials and studies of patients who have undergone long-term immunosuppression. Indicators of kidney damage associated with cyclosporin treatment were reported in 5-47% of treated subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2201502 TI - Abnormal lipoprotein composition in normolipidemic diabetic patients. AB - To see whether there are any lipoprotein abnormalities in diabetic patients without hyperlipidemia, lipoprotein composition was examined in 75 strictly normolipidemic diabetic patients. Their plasma cholesterol (chol) and triglyceride (TG) were limited to less than 6.0 and less than 1.7 mM, respectively. Body-weight- and age-adjusted normolipidemic healthy subjects served as the control group. Plasma total chol and TG and low-density lipoprotein (LDL-) and high-density lipoprotein (HDL-) chol were identical in the diabetic and control subjects. Total apolipoprotein B (apoB) in the plasma of the diabetic subjects was significantly elevated. The chol-apoB ratio in the TG-rich (very-low density + intermediate-density) lipoprotein fraction (Sf12-400) of the diabetic subjects was significantly higher than the control value, whereas LDL-apoB levels were increased and chol-apoB ratio in the LDL fraction was significantly suppressed in the diabetic subjects. Because each LDL particle contains only one apoB molecule, apoB and chol-apoB ratio in this fraction can represent particle number and chol loading of the LDL particles, respectively. Thus, these data suggest that LDL particle number is increased, and the particles are chol depleted in diabetic subjects even if they are normolipidemic. PMID- 2201503 TI - Immunosuppression in IDDM. Rationale, risks, benefits, and strategies. PMID- 2201504 TI - Brain wave on the witness stand. PMID- 2201505 TI - Meal-related insulin supply in IDDM. PMID- 2201506 TI - Cytology of pseudomyxoma peritonei: report of two cases arising from appendiceal cystadenomas. AB - Pseudomyxoma peritonei is the clinical term for the diffuse deposition of mucus within the peritoneal cavity secondary to a mucinous tumor of the ovary or appendix. This gelatinous ascites, or "jelly-belly," may result in death from loss of intestinal function and intestinal obstruction caused by peritoneal implants rather than visceral invasion. Microscopic evaluation of peritoneal fluid is frequently an initial diagnostic test; however, in a search of the recent literature we were surprised to find only one case report of the cytologic features. This prompted us to report the cytologic findings in the peritoneal fluid of two cases of pseudomyxoma peritonei arising from appendiceal mucinous cystadenomas. PMID- 2201507 TI - Papillary transitional-cell carcinoma of the upper urinary tract: a cytological review. AB - Urinary cytology is a well-accepted diagnostic procedure for bladder carcinomas but it is utilized less frequently for diagnosis of upper urinary tract tumors. Accurate diagnosis depends on a suitable specimen as well as knowledge of diagnostic traps. This review article with several case studies emphasizes the various techniques used to obtain optimal samples, correct interpretative criteria, and diagnostic pitfalls. Technological advances for objective grading and predicting the biological behavior of tumors are also discussed. PMID- 2201508 TI - Identification of Campylobacter pylori by gastric brush cytology. PMID- 2201509 TI - Sarcoidosis. AB - More than a century ago, Jonathan Hutchingson, a surgeon-dermatologist, identified the first case of sarcoidosis at King's College, London. The disease is now known as a commonplace multisystem disorder characterized by the formation of noncaseating granulomata. The diagnosis of sarcoidosis is established by recognizing clinicoradiologic findings and providing histologic evidence of non caseating granuloma. Serum angiotensin converting enzyme levels are high in about two thirds of the patients and hypercalcemia is a feature in one of every ten victims of sarcoidosis. Immunologic abnormalities include depression of cutaneous delayed-type hypersensitivity, accumulation of T-cells at the site of activity, hyperactive B-cells, and the presence of circulating immune complexes. The course and prognosis of the disease usually correlate with the mode of onset. An acute onset with erythema nodosum indicates a good prognosis and spontaneous resolution; whereas, an insidious onset may be followed by relentless, progressive fibrosis. Mortality and morbidity are caused by pulmonary fibrosis, cardiac arrhythmias, renal failure, neurologic involvement, and blindness. Corticosteroids and chloroquine relieve symptoms and suppress inflammation and granuloma formation. PMID- 2201511 TI - [Determination of blood digoxin]. PMID- 2201510 TI - [Narcolepsy]. PMID- 2201512 TI - [Embryo transfer in cattle--present status and outlook]. PMID- 2201513 TI - Thyroxine-dependent modulations of the expression of the neural cell adhesion molecule N-CAM during Xenopus laevis metamorphosis. AB - During amphibian metamorphosis, a complete remodeling of the phenotype takes place under complex hormonal control whose final effectors are thyroid hormones. This process implies the activation of coordinated programs of cell death, proliferation, migration, adhesion and differentiation. Inasmuch as the neural cell adhesion molecule N-CAM is thought to play a central role in the control of morphogenetic processes, we have studied by immunohistofluorescence and immunoblots the patterns of expression of N-CAM at different stages of Xenopus laevis metamorphosis. A scan was made of all major organs and appendages. Before the metamorphic climax, all neuronal cell bodies and processes express high levels of N-CAM. During the metamorphic climax, N-CAM expression decreases sharply on the cell bodies and processes of the peripheral nervous system (PNS) but remains high in the central nervous system (CNS). Towards the end of metamorphosis, the PNS and spinal nerves are virtually negative for N-CAM while the CNS is still positive. The optic and olfactory nerves, although myelinated, are still strongly positive for N-CAM. The lens and olfactory epithelia express N CAM throughout metamorphosis. In the brain. N-CAM is present at all times as three polypeptides of 180, 140, and 120 X 10(3) Mr; before metamorphosis some of the N-CAM is in its polysialylated form. During metamorphosis and the subsequent growth of the animal, the amount of N-CAM decreases gradually. In all polypeptides, the polysialylated form is the first to disappear. Cardiac muscle expresses high level of N-CAM from its first formation throughout metamorphosis; in contrast, the level of N-CAM in skeletal muscle is high in newly formed muscles, but decreases rapidly after myoblast fusion. The liver of adult Xenopus contains large amounts of a 160 X 10(3) polypeptide that is recognized by polyclonal and monoclonal antibodies against N-CAM. cDNA probes of Xenopus brain N-CAM recognize major transcripts of 9.2, 3.8 and 3.3 kb in Xenopus liver mRNA; these bands are different in size from those recognized in brain mRNA (9.5, 4.2 and 2.2 kb). Premetamorphic liver does not express the 160 X 10(3) form of N-CAM, which can be first detected at stage 59 and persists then through all the life of the animal. Expression of N-CAM in the liver can be induced in premetamorphic animals (stage 51-52) by a 48 h treatment with thyroxine. All hepatocytes are responsive.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2201514 TI - [Patients treated for one year with tianeptine. Results at one of the centers of South-Eastern France]. AB - Tianeptine is a new antidepressant with a tricyclic molecular structure. Its main neurochemical effect consists in an increase in serotonine re-uptake. Its efficacy as antidepressant and its good clinical safety have been confirmed in controlled trials against reference drugs. 1,231 patients with a DSM III diagnosis of major depression or dysthymic disorder were included in a long-term trial with tianeptine. 510 patients completed the one-year treatment period. The results of a subgroup of 100 patients treated in one of the centres of south-east France will be presented. 47 of these patients completed the trial. This study allowed to evaluate the therapeutic efficacy as well as the clinical safety of tianeptine during long-term prescription. Patients were treated in an open design after a 4-7 day placebo washout period. Therapeutic effects were assessed by the C.G.I. items (1 and 2), MADRS, HARS and HSCL. For the evaluation of clinical and paraclinical safety, spontaneous complaints of the patients and CGI-3 were documented; body weight, blood pressure and blood chemistry were also measured. Homogeneity between completers and non-completers was tested before statistical analysis of the clinical effects. Results of completers were analyzed using a two way ANOVA (time x subjects); Newman-Keuls tests were performed in the case of a significant time effect. End-point analysis was used to test the results of the total sample. Patients completing the trial had a mean MADRS baseline score of 32.8. Given high this score, the patients have to be considered genuinely depressed at inclusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2201515 TI - The impact of drug abuse and addiction on society. AB - Over 28 million Americans have admitted to abusing a substance in the last year alone, at a direct purchase price of over 79 billion dollars. Substance abuse and addiction have grave consequences on our existing social systems, effecting crime rates, hospitalizations, child abuse, and child neglect, and are rapidly consuming limited public funds. The intravenous drug abuser represents the fastest growing vector of HIV virus. This report focuses on the social and economic implications of substance abuse and addiction and discusses the merits and limitations of several popular solutions to the problem. PMID- 2201517 TI - Opioids and designer drugs. AB - Despite the increasing use of other illicit drugs, opioid abuse, overdose, and the ensuing medical complications continue to pose management challenges for the emergency physician. Heroin use is increasing as abusers of cocaine seek a drug to prolong cocaine's effects while blunting the postcocaine depression. Clandestine chemists have created newer, more powerful compounds--designer drugs- whose potencies are many-fold that of the presently available opioids. Aggressive airway support and use of naloxone enable the emergency physician to salvage many of these patients, leaving the many medical complications of parenteral and inhalational use as the greatest management challenge. PMID- 2201516 TI - Cocaine. AB - There has been a dramatic rise in the number of adverse medical effects related to cocaine abuse since the widespread introduction of crystallized freebase cocaine or "crack" in the mid-1980s. In particular, cardiovascular and central nervous system toxicity is becoming more widely recognized and requires aggressive medical management to prevent potentially high morbidity and mortality. PMID- 2201518 TI - Sympathomimetics. AB - Sympathomimetics have a long history of abuse. Initially amphetamines were abused for their adrenergic "rush"; now more sophisticated chemists have developed compounds that add a hallucinogenic component. Since the advent of crack and now "ice," the physician needs to recognize and treat appropriately those patients who present with the signs and symptoms of sympathetic hyperactivity. PMID- 2201519 TI - Phencyclidine. AB - Patients intoxicated with phencyclidine (PCP) present both diagnostic and management dilemmas. The clinical presentation ranges from coma to severe agitation and violence; disorientation, psychosis, catatonia and bizarre behavior can be seen. Patients are at-risk for significant medical complications such as rhabdomyolysis, seizures, and hyperthermia. This article reviews the effects and complications of PCP abuse and offers an approach to the management of these patients. PMID- 2201520 TI - LSD. AB - LSD is still readily available in the United States as a street drug of abuse. Emergency physicians may be called on to diagnose acute LSD intoxication in cases in which the history is unavailable. The typical LSD intoxication syndrome causes marked illusions of color and sound, along with a feeling of "cosmic awareness." True hallucinations only occasionally occur; the pupils invariably are massively dilated. The diagnosis may be very difficult to establish when other drugs, particularly those causing coma, are present. The toxicology laboratory can now easily detect LSD by radioimmunoassay. PMID- 2201521 TI - Volatile substances of abuse. AB - Substances that are inhaled for the purpose of recreational self-intoxication include aliphatic hydrocarbons, alkyl halides, alkyl nitrites, aromatic hydrocarbons, ethers, and ketones. All have the ability to cause asphyxia, arrhythmias, cardiovascular depression, neurologic dysfunction, and mucosal, pulmonary, and skin irritation following acute exposure and permanent neurologic damage with chronic exposure. The acute effects of alkyl halides and alkyl nitrites also include carbon monoxide poisoning and hepatorenal toxicity, and methemoglobinemia, respectively. Chronic exposure to aromatic hydrocarbons and ketones can result in liver, kidney, and bone marrow injury; myopathy, rhabdomyolysis, metabolic acidosis, and electrolyte abnormalities are further complications of chronic aromatic hydrocarbon inhalation. PMID- 2201522 TI - Plants and mushrooms of abuse. AB - The plants described earlier are only a few of those that can be misused. Most have effects similar to those of more popular synthetic drugs but can cause unpleasant side effects and unpredictable results. Identification of the offending botanic agent can be problematic. These plants are still used because most are legal to possess, and they do produce desired hallucinogenic and stimulant effects. Because the active ingredients are similar pharmacologically to agents such as LSD and amphetamine, required treatment is often similar. The challenge for the Emergency Department physician is to recognize the potential for abuse of these botanic agents, their probable side effects, and the need for appropriate, usually supportive, treatment. There are many more plants with abuse potential than can be discussed in detail in an article of this size. Table 1 lists a number of other agents that might be misused. Phenylamine hallucinogens occur in several species and include N,N-dimethyltryptamine (DMT), N monomethyltryptamine (MMT), 5-methoxy-N-N-dimethyltryptamine (5-MeO-DMT), 5 methoxy-N-monomethyltryptamine (5-MeO-DMT), 5-methoxy-N-monomethyltryptamine (5 MeO-MMT), 5-hydroxy-N-N-dimethyltryptamine (bufotenine or 5-H-DMT), and N,N dimethyltryptamine-N-oxide (DMT-N-oxide). PMID- 2201524 TI - Substance withdrawal. AB - As long as drug use and abuse persist in our society, a significant number of patients with various types of drug withdrawal will present to Emergency Departments. It is imperative that we recognize the signs and symptoms of drug withdrawal and render the appropriate treatments. Although it may be easy to recognize "skid row" alcoholics, a drug abuser with track marks on his (or her) arms or with a perforated nasal septum, the executive alcoholic, the elderly patient on chronic diazepam therapy, or the "blue collar" worker using cocaine may be more common and more elusive. Because most drug abusers use and can be dependent on multiple drugs, detoxification may need to proceed with one drug or one class of drugs at a time. Although our discussion has concentrated on the acute presentation and treatment of these symptoms for the emergency physician, we recognize that the acute treatment of withdrawal symptoms is only a small but vital part of withdrawal treatment. These patients will require chronic treatment, including social and psychologic counseling. As emergency physicians, by performing our jobs of recognition, stabilization, and counseling, we will fulfill the first critical link in the treatment of these patients. PMID- 2201523 TI - Adulterants and substitutes. AB - The presence of an adulterant in an already inherently toxic street drug leaves both the user and the emergency physician with a harsh predicament. Both may be in the dark as to the true nature of the active ingredients, or as to the clinical effects produced by these substances or combinations of substances. This creates a diagnostic and therapeutic dilemma for the treating physician, as he or she wrestles with the often contradictory clinical signals and the inescapable possibility that prescribed therapy may interact adversely with the compounds already exerting their effects. The only defense we have is an open and constantly probing thought process, which maintains an awareness of the current street drug culture, and then channels this information into the clinical decision process. PMID- 2201525 TI - Obstetric and neonatal effects of drugs of abuse. AB - With an increase in illicit drug use in North America, more fetuses are exposed to cocaine, cannabinoids, alcohol, cigarettes, and opioids. Whereas the adverse fetal effects of some agents have been established (for example, ethanol), those of other compounds are still controversial (for example, cocaine, THC). Two important trends may hamper our understanding of the potential reproductive risks of recreational drugs: 1. The clustering of many other risk factors in the same women. 2. A tendency to publish studies showing adverse reproductive fetal effects while discouraging reports of no effects by drugs and chemicals. Although short-term research has addressed some of the immediate postnatal physical and behavioral performance of these babies, much more work is needed to address the difficult questions of long-term neurobehavioral outcome in babies exposed to recreational drug abuse in utero. PMID- 2201526 TI - HIV infection and intravenous drug users. Implications for emergency services. AB - HIV-1 infection among IVDUs is increasing at a rapid rate in the U.S. Because many Emergency Departments experience many visits from patients with this risk factor, the impact on emergency services can be considerable. Because many of these patients currently have asymptomatic infection, knowledge of clinical presentations of HIV-1 infection is valuable, as the Emergency Department may be the site for the initial presentation of complications related to HIV-1. Finally, Emergency Departments may play a vital role in preventing further progression of this deadly and destructive disease among this risk group. PMID- 2201527 TI - Endocarditis in intravenous drug abusers. AB - IE due to parenteral drug use is an ever-increasing problem for physicians working in the ED. IE may present with a multitude of signs and symptoms of variable severity. Patients may complain of only vague symptoms consistent with a viral syndrome, or they may present with a neurologic or cardiovascular catastrophe. ED physicians must have a high degree of suspicion for IE whenever they evaluate a patient who could possibly be abusing drugs. PMID- 2201528 TI - Other infectious complications in intravenous drug users. The compromised host. AB - This article deals with the infectious entities, excluding acquired immunodeficiency syndrome and endocarditis, the physician is likely to encounter in the intravenous drug abuser on presentation to the Emergency Department. Multiple factors may suppress the usual diagnostic indicators. Awareness of the common infectious problems in this population and a high index of suspicion are needed to render quality care in the Emergency Department. PMID- 2201529 TI - Utility and reliability of emergency toxicologic testing. AB - Emergency physicians using toxicologic testing should learn the capabilities of their laboratories: What is detectable? What is not? What is the expected turnaround time? Do pharmacologic relationships exist? In ordering test requests, the laboratory should allow the physician to order limited test combinations, and the physician can assist the laboratory in the search for unknowns by indicating the running diagnosis and suspected drugs. Only a few drugs require quantitation in serum in order to assist in therapeutic decisions. Urine drug screening is useful in documenting intoxications due to drugs and frequently demonstrates more drugs or drugs other than those clinically expected. The impact of findings from emergency drug screening upon diagnosis and therapy appears to be low. Although comprehensive drug screening in the emergency setting has a better positive predictive value ("rule-in") than negative predictive value, toxicologic screening may be useful as a "rule-out" test in other diagnostic applications of lower prior probability. Future directions in laboratory diagnosis of the intoxicated patient are likely to include growth in new immunoassays with limited applications, but with rapid turnaround within the Emergency Department. Also, with improvements in technology, screening of serum drugs will become more common, including the discovery of more quantitative relationships between serum concentration and toxic effects. PMID- 2201530 TI - Antisera to a synthetic peptide recognize native and denatured rat estrogen receptors. AB - Specific polyclonal antisera to the rat estrogen receptor (rER) were developed using a synthetic peptide as the antigen. The peptide corresponds to amino acids 270-284 deduced from the cloned rER cDNA and has no homology to other steroid hormone receptors. Antipeptide antisera raised in rabbits specifically recognize a 67,000 mol wt protein, shown to be the rER, in Western blot experiments. In immunoprecipitation experiments, one tested antiserum bound unoccupied as well as 17 beta-estradiol-occupied rERs, indicating that this region is exposed in both receptor forms. This antiserum shows no cross-reactivity with rat progesterone or glucocorticoid receptors. Cross-reactivity with rabbit, human, and, to a lesser extent, bovine ERs was observed. PMID- 2201531 TI - Glucagon inhibits insulin activation of glucose transport in rat adipocytes mainly through a postbinding process. AB - Incubation of rat adipocytes with 1 microM glucagon plus adenosine deaminase (5 micrograms/ml) inhibited maximally insulin-stimulated 3-O-methyl-D-glucose (MeGlc) transport by approximately 70%, concomitant with 30% and 55% decreases in insulin binding and cellular ATP, respectively. In contrast, under conditions where cellular ATP levels are well preserved (i.e. high albumin concentration in the medium), the inhibition of transport was reduced to about 30%, but that of insulin binding was not. Because depletion of the cellular ATP level by more than 60% by metabolic inhibitors induced 40% or more inhibition of insulin-stimulated MeGlc transport, the greater inhibition of the transport with the low albumin concentration appears to be caused in part by the secondary effect of ATP loss. The relationship between the amount of cell-bound insulin and hormone-stimulated transport activity showed that glucagon does not modulate insulin action at the step of insulin binding to its receptors. Furthermore, glucagon suppressed insulin-stimulated MeGlc transport, mainly through an attenuation of the hormone induced increase in maximum velocity. The data show that glucagon modulates the process of signal transduction of insulin action. However, the possibility that glucagon directly modulates the process of translocation or the intrinsic activity of the glucose transporters cannot be eliminated. PMID- 2201532 TI - Monoclonal and polyclonal antibodies to human progesterone receptor peptide-(533 547) recognize a specific site in unactivated (8S) and activated (4S) progesterone receptor and distinguish between intact and proteolyzed receptors. AB - We have synthesized three peptides with amino acid sequences corresponding to amino acids 533-547, 597-611, and 765-779 of the human progesterone receptor (hPR). These peptides were conjugated to keyhole limpet hemocyanin and injected into mice and rabbits to develop antibodies to hPR. Antibodies to the undenatured form of PR were elicited only by the peptide with amino acid sequence 533-547. Fusion of SP2/0 myeloma cells with spleen cells from mice immunized with this peptide produced several active clones. Rabbit sera from immunized animals produced one antiserum that reacted with the undenatured form of PR. One monoclonal antibody (PR-AT 4.14) and one antiserum (PR-AT533) raised against peptide-(533-547) were characterized. Binding of these antibodies to the undenatured form of PR was demonstrated by analysis of the antibody-receptor complexes on sucrose density gradients and by immunoprecipitation techniques. Binding of PR to the antibodies was inhibited by excess peptide. The antibodies did not react with estrogen, glucocorticoid, or androgen receptors, but recognized PR from human breast cancer as well as calf, rabbit, mouse, and rat uteri, indicating that this epitope was conserved among these species. Based on sucrose density gradient analysis of PR prepared and labeled in the presence of proteolysis inhibitors and sodium molybdate, the antibodies bound to a site on the intact undenatured PR, but failed to bind to partially degraded steroid binding form of the receptor, suggesting that the antibody-binding domain is at or near a site sensitive to proteolysis. PMID- 2201533 TI - An organ culture system for the study of programmed cell death in the rat ventral prostate. AB - Glandular epithelial cells of the rat ventral prostate undergo programmed cell death in vivo following androgen ablation. Fragmentation of the prostatic DNA is an irreversible commitment step in this programmed cell death process. The amount of prostatic DNA fragmentation thus is a quantitative measure of the number of androgen-dependent prostatic glandular cells undergoing programmed death. An in vitro organ culture system was devised for determining rates of prostatic programmed cell death based upon the daily percentage of prostatic DNA fragmentation. To do this, rats were castrated and 2 weeks later treated in vivo for 3 days with exogenous androgen replacement to maximally stimulate DNA synthesis (i.e. proliferation) of the ventral prostatic glandular cells. In vitro organ cultures were established from these ventral prostates and the DNA of these explants was 125I-labeled by incubation in media containing [125I]iododeoxyuridine [( 125I]IDU). Using this in vivo-in vitro DNA labeling technique, greater than 85% of the [125I]IDU radioactivity was incorporated into DNA of the prostatic explants glandular cells. The decrease in 125I-radioactivity from prostatic explants was determined for over a 10-day period of organ culture. Using regression analysis of these data, the daily rate of programmed cell death of the glandular cells was determined. To test the validity of the method, organ cultures were maintained in media capable of inducing either necrotic (i.e. HgCl2 containing media) or programmed cell death (i.e. media lacking testosterone) and the daily decrease in the percentage of [125I]IDU retained in the tissue determined. In addition, the morphologic appearance of necrotic vs apoptotic cell death (i.e. programmed) was quantitated and compared to the [125I]IDU data. These studies demonstrated that this [125I]IDU labeled rat prostatic organ culture system can be used as an in vitro screen to quantitate the ability of various test agents to activate the programmed cell death pathway in prostatic glandular cells. PMID- 2201534 TI - Expression of atypical and classical insulin receptors in Chinese hamster ovary cells transfected with cloned cDNA for the human insulin receptor. AB - Human placenta and IM-9 lymphocytes contain subpopulations of atypical insulin receptors which differ from classical insulin receptors in their higher binding affinity for insulin-like growth factors I and II (IGF-I and IGF-II). Both types of insulin receptors may be derived from different but related genes, or may represent alternative post-translational modifications of the same gene product. To test these possibilities, we have examined the IGF binding characteristics of the human insulin receptors expressed in Chinese hamster ovary (CHO) cells which had been stably transfected with cloned human insulin receptor cDNA (CHO-T cells). The parent CHO cells contained 3 x 10(3) rodent insulin receptors/cell, and the CHO-T cells, 2.0 x 10(6) human insulin receptors/cell. Competition binding studies showed that the binding of [125I]IGF-I and [125I]multiplication stimulating activity (MSA/rat IGF-II) to parent CHO cells was primarily to type I and II IGF receptors, which cross-react poorly or not at all with insulin. However, competition binding studies with CHO-T cells showed that [125I]IGF-I binding was displaced 60-70%, and [125I]MSA binding, 50-55%, by low concentrations of insulin (20 ng/ml) and no further by higher concentrations of insulin (500 ng/ml). The insulin-insensitive IGF binding sites corresponded to the rodent type I and II IGF receptors; the insulin-sensitive IGF binding sensitive sites resembled the human atypical insulin receptors in that they bound IGF-I and MSA with moderately high affinity and reacted with insulin, MSA, and IGF-I in that order of potency. Atypical insulin receptors were also demonstrated by insulin-sensitive [125I]IGF-I and [125I]MSA binding to solubilized CHO-T proteins adsorbed to microtiter wells coated with monoclonal antibodies specific for the human insulin receptor. These results suggest that atypical human insulin receptors are generated by differential post-translational processing of the same gene product as classical human insulin receptors. PMID- 2201535 TI - Regulation of antitrypsin and antichymotrypsin synthesis by MCF-7 breast cancer cell sublines. AB - We have examined the synthesis of the protease inhibitors alpha 1-antitrypsin (alpha 1-AT) and alpha 1-antichymotrypsin (alpha 1-ACHY) by variants of the MCF-7 human breast cancer cell line. Spent medium from MCF-7 203P cells, grown in the absence of serum, was found to contain immunoreactive alpha 1-AT and alpha 1-ACHY by Western blotting. In the presence of 10(-8) M estradiol, levels of both inhibitors were increased 3- to 6-fold. Incubation of spent medium with [125I]trypsin or [125I]chymotrypsin resulted in the formation of stable 75- and 90-kDa complexes identical to the complexes formed between these proteases and the protease inhibitors in plasma, showing the release of active protease inhibitors by MCF-7 cells in culture. Immunoprecipitation of 35S-labeled proteins from the medium of cells grown in the presence of [35S]methionine yielded comparable results, confirming hormonally sensitive synthesis of both protease inhibitors. Northern blot analysis suggests that stimulation of estradiol occurs at the level of transcription. Tetradecanoyl phorbol acetate (50 ng/ml) also stimulated alpha 1-AT and alpha 1-ACHY synthesis 2- to 4-fold, suggesting the involvement of protein kinase-C. Comparison studies with MCF-7 cell sublines ML, BK, 203P, and 300P (a variant spontaneously appearing after 100 passages of 203P) show a wide variation in synthesis of alpha 1-AT and alpha 1-ACHY proteins; sublines 203P and 300P synthesize both inhibitors, the ML subline synthesizes detectable amounts only of alpha 1-ACHY, while no detectable synthesis of either inhibitor was seen in the BK subline. Similar results were obtained for protease inhibitor mRNA transcription by Northern blotting, although low levels of alpha 1 AT mRNA transcription by the ML subline and of alpha 1-AT and alpha 1-ACHY mRNA transcription by the BK subline could be detected. PMID- 2201536 TI - The estradiol-induced surge of gonadotropin-releasing hormone in the ewe. AB - Previous studies suggest two roles for estradiol in inducing the LH surge in ewes: a neural action to evoke a sudden release of GnRH and a pituitary action to maximize response to GnRH. We tested two hypotheses: a follicular phase estradiol rise induces a GnRH surge; and the surge-inducing action of estradiol does not vary with season. In the breeding season, ewes in the midluteal phase of the estrous cycle were ovariectomized and treated with implants producing luteal phase levels of estradiol and progesterone, and an apparatus was surgically installed for later sampling of pituitary portal blood. At the normal time of luteolysis (1 week later), progesterone implants were removed, simulating luteal regression. Ewes were divided into two groups: estradiol implants also removed (n = 6) and estradiol implants added 16 h after progesterone removal to produce a rise in estradiol to levels that mimic those that circulate in the late follicular phase (n = 6). In anestrus, the estradiol rise treatment was replicated in ewes (n = 5) after an artificial luteal phase produced by sequential insertion and subsequent removal of progesterone implants. Regardless of season, the LH surge induced by estradiol was invariably accompanied by a massive GnRH surge, ranging from 73- to 394-fold over presurge values. The GnRH and LH surges began together, but the GnRH surge continued well beyond the surge of LH. There was no seasonal difference in time course or amplitude of the GnRH surge. Control ewes not treated with estradiol exhibited regular pulses of LH and GnRH every 1-2 h, but no surge of either hormone. We conclude that, regardless of season, a rise in estradiol to late follicular phase levels initiates a large and abrupt GnRH surge coincident with the onset of the LH surge. The LH surge ends despite continued elevation of GnRH. PMID- 2201537 TI - Ontogeny and pituitary regulation of testicular growth hormone-releasing hormone like messenger ribonucleic acid. AB - The testis is rich in central nervous system-type neuropeptides, including a GH releasing hormone (GHRH)-like substance. We examined the ontogeny and pituitary regulation of testicular GHRH-like mRNA (t-GHRH mRNA) and compared this to expression of insulin-like growth factor-I (IGF-I) and IGF-II mRNA in developing testis. t-GHRH mRNA was measured by dot blot hybridization and quantitated using a hypothalamic GHRH cRNA standard. t-GHRH mRNA was not detectable in Northern blots in fetal testis on day 19 of gestation, but was present in low but detectable amounts in testicular dot blots on day 2 of life (0.44 pg/micrograms total RNA). Levels of the RNA increased beginning on day 21 (1.72 +/- 0.23 pg/micrograms total RNA) and reached adult levels by day 30 (4.96 +/- 0.84 pg/micrograms total RNA). The GHRH species on Northern analysis was about 1750 nucleotides at all ages examined; there was a larger species of about 3350 nucleotides seen on days 65 and 90. There was no correlation between the ontogeny of t-GHRH mRNA and either IGF-I or IGF-II mRNAs, which were maximally expressed in the testes of day 2 animals and decreased with age. To examine the influence of the pituitary gland on t-GHRH mRNA, levels of the mRNA were measured in the tests of hypophysectomized animals and age-matched controls. In animals hypophysectomized on day 21 and killed on day 42 and in animals hypophysectomized on day 42 and killed on day 63, there was marked diminution of t-GHRH mRNA (19 +/ 5% and 9 +/- 2% of age-matched controls, respectively). In contrast, in animals hypophysectomized on day 65 and killed on either day 80 or 90, there was a much smaller difference in levels of t-GHRH mRNA compared to values in control animals (73 +/- 20%). This was unlike the effect of hypophysectomy on testicular IGF-I mRNA, where uniform diminution was seen in all three groups. Because GH is important in the regulation of hypothalamic GHRH mRNA, we examined the effects of administration of recombinant human GH on the reinduction of t-GHRH mRNA after hypophysectomy and compared this to the reinduction of IGF-I mRNA. Neither t-GHRH mRNA nor testicular IGF-I mRNA increased in hypophysectomized animals treated with GH. Our results indicate that t-GHRH mRNA is developmentally regulated, and that the hypothalamic-pituitary axis is important in its expression.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2201538 TI - Investigation of the mechanism by which insulin-induced hypoglycemia decreases luteinizing hormone secretion in ovariectomized ewes. AB - Ovariectomized ewes were treated with 100 IU insulin, iv, which caused reductions in blood sugar and plasma LH concentrations. The effect was prevented by the infusion (iv) of glucose, suggesting that neuroglycopenia and not a direct action of insulin was the cause of reduced LH secretion. An iv infusion of naloxone (40 mg/h for 2 h), which commenced 25 min before the insulin injection, blocked the inhibitory effect of insulin on LH secretion, but it did not prevent the decrease in plasma glucose concentrations. In this treatment group and in a group treated only with naloxone, the opioid antagonist significantly stimulated LH secretion. To determine whether CRF might be involved in the insulin-induced decrease in LH secretion, 50 micrograms CRF were injected into ovariectomized sheep. Despite producing very high circulating concentrations of CRF within 2 min of injection and the stimulation of cortisol secretion during most of the 4-h posttreatment period, plasma LH levels were not affected. In addition, the intracerebroventricular administration of 10 micrograms CRF or 10 micrograms CRF plus 10 micrograms arginine vasopressin (AVP) did not affect LH secretion. These observations suggest that insulin-induced hypoglycemia decreased LH secretion by neuroglycopenia. This may involve an opioidergic mechanism, but does not involve activation of the hypothalamo-pituitary-adrenocortical axis. PMID- 2201539 TI - Deoxyribonucleic acid synthesis in cultured adult rat pancreatic B cells. AB - Previous studies in rodent islets have suggested the existence of a small number of proliferating islet cells. Since islet tissue is composed of endocrine as well as nonendocrine cells, we examined whether the DNA synthesis that is detectable in intact islets in vitro corresponds to an activity of islet B cells, islet endocrine non-B cells and/or nonendocrine islet cells. DNA synthesis was quantified by [3H]thymidine incorporation in trichloracetic acid precipitable material, by nuclear thymidine labeling in autoradiographs, and by nuclear bromodeoxyuridine fluorescence. Adult islet endocrine purified B cells, as well as other endocrine islet cells, incorporated 1 to 2 fmol thymidine/1000 cells, which is 3 times lower than intact islet tissue and 30 times lower than nonendocrine islet cells. Addition of 10% fetal calf serum did not increase DNA synthesis in purified endocrine islet cells but doubled it in intact islets and enhanced it 8-fold in nonendocrine islet cells. The higher thymidine incorporation in intact islets was due to the presence of nonendocrine cells. An increase in medium glucose concentration from 100 to 200 mg/100 ml doubled the thymidine incorporation in purified islet B cells, but not in other endocrine islet cells; no concomitant increase in the number of thymidine or bromodeoxyuridine-labeled nuclei was observed. A phenomenon of glucose-stimulated DNA repair was not excluded. Using three different methods, we have found no evidence for a proliferating activity of adult rat islet B cells under the selected in vitro conditions of this study. PMID- 2201540 TI - Influence of insulin on albumin and non-albumin protein fractional synthetic rates in post-absorptive type I diabetic patients. AB - Two 8-h primed continuous infusions of L-[1-13C] leucine were used to determine fractional synthesis rates of albumin and non-albumin plasma protein in post absorptive Type I diabetic patients during insulin infusion and its withdrawal. Fractional protein synthetic rates were calculated from the rate of incorporation of 13C-label into protein and employing plasma 13C-alpha-ketoisocaproic acid enrichment to represent the precursor pools label. Incorporation of 13C into albumin and non-albumin plasma protein was linear over the latter 6 h of the 8-h L-[1-13C] leucine infusion. Fractional synthetic rates of plasma albumin and non albumin proteins were similar during insulin withdrawal and its infusion. The increased whole-body protein synthesis observed during insulin withdrawal in Type I diabetic patients appears unrelated to events in albumin and non-albumin plasma protein fractions. These data are further evidence that insulin per se does not stimulate protein synthesis in man. PMID- 2201541 TI - Differences in side effects between a conventional carbamazepine preparation and a slow-release preparation of carbamazepine. AB - The aim of this double-blind cross-over study was to investigate whether side effects of carbamazepine (CBZ) could be reduced by using a slow-release CBZ preparation. Twenty-one adult patients with epilepsy who had side effects related to the use of CBZ took part in the trial. Patients were randomized to receive either a conventional (C) or slow-release (SR) CBZ preparation for 3 months and were then switched over to the other preparation for another 3 months. The daily dose and dosing frequency of CBZ were kept the same as before the study. The quality and severity of side effects were assessed monthly using a scored questionnaire containing questions about systemic toxicity (STRS) and neurotoxicity (NTRS). Twenty patients could be evaluated. The mean total values of NTRS of 3 monthly visits on each drug were significantly less during SR than during C treatment (P less than 0.05). All the items of NTRS scored lower during SR therapy, and the difference was significant for the occurrence of headache, dizziness and disturbances of vision, speech and coordination. The total score of STRS was also lower during SR, but the difference was not significant. Eleven patients preferred SR, 3 preferred C and 6 patients estimated the periods to be equal. In conclusion, a slow-release preparation of CBZ can render fewer side effects than conventional CBZ preparations. PMID- 2201542 TI - Application of a capture enzyme immunoassay in an outbreak of waterborne giardiasis in the United Kingdom. AB - A capture enzyme immunoassay (EIA) for the detection of Giardia lamblia antigen was used to examine 136 fecal samples collected during an outbreak of waterborne giardiasis in a city in the UK. Six cases of Giardia lamblia infection were detected that had previously not been diagnosed by microscopy. The capture EIA provides an efficient means of processing large numbers of samples for prompt and accurate assessment of an epidemic. It may also facilitate rapid tracing of epidemic sources. PMID- 2201543 TI - Evidence for a calsequestrin-like calcium-binding protein in human spermatozoa. AB - Human spermatozoa were investigated for the presence of protein(s) recognized by antibodies against calsequestrin, the high capacity, moderate affinity Ca2(+) binding protein, originally described in striated muscle fibers. Western immunoblots of detergent-soluble sperm extracts probed with polyclonal antibodies raised against human skeletal muscle calsequestrin identified a strongly cross reactive protein. This protein resembles muscle calsequestrin in many respects. In fact, its migration in sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) is pH dependent, its apparent molecular mass being 64 kDa in alkaline SDS-PAGE and 44 kDa in neutral SDS-PAGE; its isoelectric point is acidic (4.6); it is metachromatically stained blue by the carboxycyanine dye, Stains-All; it is a Ca2(+)-binding protein (45Ca blot overlay). Indirect immunofluorescence experiments showed that the immunoreactive protein has an intracellular localization confined to the tail mid-piece. From these findings we conclude that human sperm cells express a protein structurally and antigenically related to skeletal muscle calsequestrin; a basis for a novel interpretation of Ca2(+)-mediated events in spermatozoa is thus provided. PMID- 2201544 TI - Purification of Drosophila hsp 83 and immunoelectron microscopic localization. AB - Heat-shock protein (hsp) 83 was purified from Drosophila culture cells. Analysis by gel filtration revealed that this hsp exists in a dimeric form under nondenaturing conditions. Monoclonal and polyclonal antibodies produced against this hsp have been used to determine its intracellular localization by indirect immunofluorescence and immunogold electron microscopy in normal cells, after heat shock, during recovery and after a second heat shock. Under normal conditions, hsp 83 is predominantly cytoplasmic. Immunogold labeling reveals that this hsp is associated with vacuole-like structures containing numerous dense bodies. In addition, hsp 83 is detected, albeit at a lower level, in the nucleus where it is found within the network of perichromatin ribonucleoprotein (RNP) fibrils. This distribution changes during heat shock: hsp 83 is then found in increased concentrations at the cell periphery close to the plasma membrane. After a recovery period, hsp 83 appears associated with the nuclear membrane and/or with the neighboring endoplasmic reticulum. Following a second heat shock at 37 degrees C after recovery, a renewed deposition of hsp 83 is observed at the cell periphery. A small population of cells also shows an increased concentration of this protein in the nucleus. This intracellular distribution of hsp 83 is consistent with its reported association with various cellular proteins and suggest that this hsp may be involved in their intracellular transport and/or in the modulation of their activity. PMID- 2201545 TI - Effects of phorbol esters on cytoskeletal proteins in cultured bovine chromaffin cells: induction of neurofilament phosphorylation and reorganization of actin. AB - Bovine chromaffin cells normally express mostly nonphosphorylated neurofilaments (NFs) in primary culture, and thus provide a unique model for examining the kinase capable of phosphorylating these proteins in situ. The phorbol ester 12-O tetradecanoylphorbol-13-acetate (TPA) which activates protein kinase C induced NF phosphorylation both in the perikaryon and in neuritic extensions of neurite bearing cells as judged by immunofluorescence using monoclonal anti-NF antibodies which distinguish between phosphorylated and nonphosphorylated epitopes. NF phosphorylation was suppressed by pretreating the cells with sphingosine, an inhibitor of protein kinase C, and was not observed in the presence of the phorbol ester. 4 alpha-phorbol-12,13-didecanoate (PDD) which does not activate protein kinase C, arguing that protein kinase C was responsible for the observed phosphorylation. Immunochemical analysis of cytoskeletal extracts indicated that TPA induced a 3 to 6-fold increase in NF phosphorylation and showed that the 150,000 dalton NF subunit was the principal protein kinase C substrate. In addition to the TPA effect on NF phosphorylation, TPA provoked a reversible membrane ruffling, which eventually resulted in a flattening of chromaffin cells. These morphological alterations were linked with actin patching and the development of stress fibers, respectively. Sphingosine blocked the TPA-induced membrane ruffling and actin patching, and these phenomena were correlated with increased protein kinase C activity. In contrast, there was no change in the localization of microtubules and NFs. The actin reorganization and NF phosphorylation induced by TPA suggest that at least two distinct proteins of the neuronal cytoskeleton are susceptible to the influence of protein kinase C activation. It remains to be established whether protein kinase C plays a role in the regulatory mechanism controlling actin organization and neurofilament phosphorylation during neuronal differentiation. PMID- 2201546 TI - A malaria heat-shock-like determinant expressed on the infected hepatocyte surface is the target of antibody-dependent cell-mediated cytotoxic mechanisms by nonparenchymal liver cells. AB - Cultured hepatic stages of Plasmodium falciparum and P. yoelii and with a monoclonal antibody recognizing a C-terminal fragment of the P. falciparum heat shock-like protein (Pfhsp70) revealed that synthesis of this antigen first occurs during intrahepatic development of the parasite, at the two nuclei stage. Using a variety of techniques, including scanning electron microscopy, we observed that this antigenic determinant was expressed on the infected hepatocyte membrane. Its participation in antibody-dependent cell-mediated cytotoxicity was investigated. While no effect was obtained with peripheral blood cells, we found that 25% of the schizonts were specifically lysed when using spleen cells at a killer/target ratio of 30/1. More interestingly, with nonparenchymal liver cells, up to 50% of the hepatic parasites disappeared with a killer/target ratio of 10/1. PMID- 2201547 TI - The ontogeny of human lymphocyte recirculation: high endothelial cell antigen (HECA-452) and CD44 homing receptor expression in the development of the immune system. AB - In the present report we have studied the expression of a lymphocyte homing receptor, the CD44 antigen, and of HECA-452, a high endothelial-specific antigen, during the development of the human immune system. We found that prothymocyte immigrants of the thymus already expressed the CD44 antigen. Similarly, the first peripheral T lymphocytes in fetal lymph nodes, tonsils and gut-associated lymphoid tissue were also CD44+. Cortical thymocytes and germinal center cells were CD44-. CD44 antigen expression was, thus, not limited to mature recirculating lymphocytes. This suggests that CD44 may not only be involved in recirculation of mature lymphocytes but also in the migration of prothymocytes to their site of maturation, i.e. the thymus. High endothelial venules (HEV) were not demonstrable at the early onset of lymphocyte immigration into the developing lymphoid organs. However, when large-scale influx of lymphocytes occurred, it paralleled HEV development. HECA-452 antigen expression preceded the morphological transformation of endothelium into a HEV phenotype. Expression of this antigen therefore, independently reflected the specialized nature of high endothelium. In a patient with complete DiGeorge's syndrome normal HEV developed, indicating that the presence of T lymphocytes is not a requirement for HEV development. Interestingly, a subpopulation of venules located in the thymic medulla near the cortico-medullary junction expressed the HECA-452 antigen. These vessels, which had flat or intermediately high endothelium, are probably involved in lymphocyte migration to the thymus. PMID- 2201548 TI - Ontogeny of the humoral response to group A streptococcal carbohydrate: class and IgG subclass composition of antibodies in children. AB - We determined isotypes of natural antibodies to streptococcal group A carbohydrate (A-CHO) in sera from 101 children between 1 and 16 years of age, using a calibrated enzyme-linked immunosorbent assay system. Anti-A-CHO IgM could be detected in all but one sera. Median levels increased with age and were highest between 8 and 12 years. IgG antibodies were present at low concentrations up to the age of 4 years, and consisted predominantly of the IgG1 subclass. Between 4 and 8 years, concentrations of anti-A-CHO IgG markedly increased and median levels continued to increase through age 12-16. Anti-A-CHO IgG1 levels closely followed the pattern of IgG antibody concentrations. The number of IgG2 antibody positive sera was low in young children, as expected. In the 8-12 year age group and later, anti-A-CHO IgG2 was present in more than half of the samples, and in children between 12 and 16, medians of IgG2 and IgG1 antibodies were similar. Sera containing anti-A-CHO IgG3 were rare in children up to 4 years of age, but in the group of 4-8-year-old children, this subclass was detectable in 36% and later in up to 77% of the sera. Thus, the IgG response to A-CHO showed a clear maturation during childhood, involving the subclasses IgG1, IgG2 and IgG3. There were no significant differences in A-CHO levels between boys and girls. PMID- 2201549 TI - A multiple antigen peptide from the repetitive sequence of the Plasmodium malariae circumsporozoite protein induces a specific antibody response in mice of various H-2 haplotypes. AB - The major repetitive epitopes of the surface circumsporozoite (CS) protein of malaria sporozoites represent candidates for the development of subunit vaccines against malaria. However, previous experimental work has shown that repetitive peptides from the CS proteins of Plasmodium falciparum, P. vivax, P. yoelii and P. berghei are immunogenic only in mice with the H-2b or H-2k haplotype. This led to the conclusion that strong T helper epitopes from the non-repetitive CS sequences were required in the design of sporozoite vaccines. In the present study, we investigated the immunogenicity in mice of a octa-branched multiple antigen peptide (MAP) containing repeats of the CS protein of the human malaria parasite, P. malariae, [MAP8(NAAG)6], and found that mice with an H-2b, H-2d, H 2k, H-2f, H-2q, and H-2s haplotype produced anti-peptide antibodies after immunization and that only H-2r mice were nonresponsive. This antibody response, not induced in athymic H-2b nu/nu mice, was directed against the (NAAG) sequence, but not against the lysine core of the MAP construct. Finally, when covalently linked to a synthetic polymer of the repetitive (NANP) sequence of the P. falciparum CS protein, [MAP8(NAAG)6] behaved as a carrier molecule for the production of anti-(NANP)n antibodies in H-2d and H-2k mice, genetically nonresponder to the (NANP)n sequence. Should this wide immunogenicity of the P. malariae CS (NAAG) repetitive sequence also apply to humans, it might be considered for the design of multivalent subunit malaria vaccines. PMID- 2201551 TI - DMSO and retinoic acid induce HL-60 differentiation by different but converging pathways. AB - The expression of c-myc and two calcium-binding proteins, MRP8 and MRP14, has been analyzed in wild-type and differentiation-resistant HL-60 variants. In HL-R5 cells, resistant to the induction of differentiation by retinoic acid but not DMSO, the characteristic c-myc down-regulation which is associated with HL-60 differentiation, as well as increased levels of MRP8 and MRP14, is detectable only after DMSO treatment. By contrast HL-D4 cells, which were selected for resistance to the induction of differentiation by DMSO alone, are actually resistant to both DMSO and retinoic acid. However, treatment of HL-D4 cells with DMSO results in a transient c-myc down-regulation in the absence of either growth arrest or induction of differentiation. Neither agent can induce an increase in the level of either MRP8 or MRP14 in HL-D4. The resistance of HL-D4 cells to DMSO and retinoic acid, and the different effects of these agents on c-myc RNA levels, despite their common effect on the expression of MRP8 and MRP14, suggest that the two agents act through different pathways which coverage before the onset of myeloid differentiation in HL-60 cells. PMID- 2201550 TI - Nonmuscle and smooth muscle myosin isoforms in bovine endothelial cells. AB - A panel of monoclonal antibodies, specific for human platelet (NM-A9, NM-F6, and NM-G2) and for bovine smooth muscle (SM-E7) myosin heavy chains (MHC), were used to study the composition and the distribution of myosin isoforms in bovine endothelial cells (EC), in vivo and in vitro. Using indirect and double immunofluorescence techniques, we have found that in the intact aortic endothelium there is expression of nonmuscle MHC (NM-MHC), exclusively. By contrast, hepatic sinusoidal endothelium as well as cultured bovine aortic EC (BAEC) in the subconfluent phase of growth show coexistence of NM- and smooth muscle MHC (SM-MHC) isoforms. SM myosin immunoreactivity disappears when cultured BAEC become confluent. In this phase of cell growth, NM-MHC isoforms are localized differently within the cells, i.e., in the cytoplasm around the nucleus or in the cortical, submembranous region of EC cytoplasm. A third type of intracellular distribution of NM-MHC immunoreactivity was evident in the cell periphery of binucleated, confluent BAEC. These data indicate that (1) several myosin isoforms are differently distributed in bovine endothelia; and (2) SM myosin expression and the specific subcellular localization of NM myosin isoforms within EC might be regulated by cell-cell interactions. PMID- 2201552 TI - Characterization of the growth of murine fibroblasts that express human insulin receptors. I. The effect of insulin in the absence of other growth factors. AB - The effect of insulin on the growth of murine fibroblasts transfected with an expression vector containing human insulin receptor cDNA (NIH 3T3/HIR) and the parental cells (NIH/3T3) was characterized. Insulin in the absence of other mitogens increased the rate of incorporation of thymidine into NIH 3T3/HIR cells with a half-maximal response occurring at an insulin concentration of 35 ng/ml and a maximal response that was equivalent to that elicited by 10% fetal calf serum. The thymidine incorporation rate was increased by 12 h, was maximal at approximately 16 h, and returned to basal rates at 24 h after the addition of insulin. Insulin induced a maximum of 65% of cells to incorporate thymidine. The increased DNA synthesis was accompanied by net growth. Addition of insulin to the NIH 3T3/HIR cells resulted in increased DNA content with a half-maximal response occurring at approximately 30 ng/ml insulin and a maximal response equivalent to that elicited by serum. An increase in cell number detected after the addition of insulin to the NIH 3T3/HIR suggests that the cells had progressed through mitosis. Insulin did not increase the rate of thymidine incorporation, DNA content, or number of the parental NIH 3T3 cells. These data show that insulin, in the absence of a second mitogen, is able to induce NIH 3T3/HIR fibroblasts to traverse the cell cycle. PMID- 2201553 TI - Characterization of the growth of murine fibroblasts that express human insulin receptors. II. Interaction of insulin with other growth factors. AB - The effects of insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and insulin on DNA synthesis were studied in murine fibroblasts transfected with an expression vector containing human insulin receptor cDNA (NIH 3T3/HIR) and the parental NIH 3T3 cells. In NIH 3T3/HIR cells, individual growth factors in serum-free medium stimulated DNA synthesis with the following relative efficacies: insulin greater than or equal to 10% fetal calf serum greater than PDGF greater than IGF-1 much greater than EGF. In comparison, the relative efficacies of these factors in stimulating DNA synthesis by NIH 3T3 cells were 10% fetal calf serum greater than PDGF greater than EGF much greater than IGF-1 = insulin. In NIH 3T3/HIR cells, EGF was synergistic with 1-10 ng/ml insulin but not with 100 ng/ml insulin or more. Synergy of PDGF or IGF-1 with insulin was not detected. In the parental NIH 3T3 cells, insulin and IGF-1 were found to be synergistic with EGF (1 ng/ml), PDGF (100 ng/ml), and PDGF plus EGF. In NIH 3T3/HIR cells, the lack of interaction of insulin with other growth factors was also observed when the percentage of cells synthesizing DNA was examined. Despite insulin's inducing only 60% of NIH 3T3/HIR cells to incorporate thymidine, addition of PDGF, EGF, or PDGF plus EGF had no further effect. In contrast, combinations of growth factors resulted in 95% of the parental NIH 3T3 cells synthesizing DNA. The independence of insulin stimulated DNA synthesis from other mitogens in the NIH 3T3/HIR cells is atypical for progression factor-stimulated DNA synthesis and is thought to be partly the result of insulin receptor expression in an inappropriate context or quantity. PMID- 2201554 TI - Hematopoiesis in limiting dilution cultures: influence of cytokines on human hematopoietic progenitor cells. AB - We have modified a limiting dilution liquid culture assay, used to quantify hematopoietic progenitor frequency, to simultaneously assess cellular proliferation and differentiation. The frequency of colonies from cord blood obtained with recombinant human interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination was comparable to cultures with IL-3 alone. However, IL-3 and GM-CSF in combination were synergistic for higher granulocyte proliferation than IL-3 alone, indicating that enhanced granulocyte production occurred via action of GM-CSF on progenitor cell populations already stimulated into proliferation by IL-3. Peak proliferation was evident at 4 weeks in culture, with metamyelocytes predominating; at 6 weeks, mostly neutrophils and eosinophils were present, and eosinophils were more numerous in cultures with IL 3. Increasing concentrations of erythropoietin (epo) in liquid culture with IL-3 or GM-CSF decreased absolute granulocyte yield while stimulating erythroid proliferation. The influence of epo on lineage morphology for cells plated in methylcellulose was markedly less evident by comparison, arguing against an inductive effect of epo to shift progenitor cell lineage. This liquid culture methodology may be a useful tool for preclinical screening of cytokines on human hematopoietic progenitor cells. PMID- 2201555 TI - Heterogeneity of recombinant granulocyte-macrophage colony-stimulating factor mediated enhancement of neutrophil adherence to endothelium. AB - Human recombinant (r) and chemically synthesized granulocyte-macrophage colony stimulating factor (GM-CSF) was found to enhance the attachment of neutrophils to monolayers of human umbilical vein endothelial cells by direct action upon the neutrophil. Using synthetic peptides of GM-CSF with truncated amino and carboxy termini, a region between amino acids 14 and 24 was found to be essential for neutrophil attachment. In analysis of the response of neutrophils from individual donors, a heterogeneity in their capacity to respond to GM-CSF by increased adherence was observed. The level of response to GM-CSF did not depend on receptor number. However, a positive correlation (r = 0.58) was found between the ability to respond to GM-CSF and the level of response to tumor necrosis factor- suggesting a link between the responses of neutrophils to these two cytokines. The stimulation of neutrophil adhesiveness to endothelial cells by rGM-CSF and the heterogeneity in donor response may have important implications for the clinical administration of GM-CSF. PMID- 2201556 TI - Multiple forms of lactoferrin in normal and leukemic human granulocytes. AB - Multiple forms of lactoferrin (Lf) were detected in granulocytes isolated from normal individuals and patients with granulocytic leukemias. One class of Lfs bound iron; a second class did not bind iron but possessed potent ribonuclease activity. The different forms of Lf were similar, if not identical, in their physical, chemical, and antigenic properties. The multiple forms of Lf may relate to the various functions ascribed to the molecule. PMID- 2201557 TI - Effect of phorbol myristate acetate on c-myc, beta-actin, and FV gene expression in morphologically recognizable human megakaryocytes: a kinetic analysis employing in situ hybridization. AB - Phorbol esters are reported to modulate numerous megakaryocyte maturation maturation parameters, but the effects of these compounds on normal human megakaryocyte gene expression are unknown. We therefore determined if phorbol myristate acetate (PMA)-induced changes in megakaryocyte gene expression could be detected and semi-quantified in single cells using the techniques of in situ hybridization and photodensitometry. Megakaryocytes were isolated from normal human bone marrow by counterflow centrifugal elutriation. After 2, 15, and 24 h of culture in 8 nM PMA, megakaryocytes were probed by in situ hybridization with biotin-11-dUTP-labeled cDNA probes for human c-myc, beta-actin, and coagulation cofactor V (FV) mRNA. Hybridization was detected by an enzyme-catalyzed colorimetric reaction that was photometrically quantified as an inverse function of light transmission through labeled cells. In control megakaryocytes, steady state levels of c-myc and FV mRNA did not change over the 24-h observation period, whereas that of beta-actin appeared to increase slightly. In contrast, after 2 h of exposure to 8 nM PMA, a statistically significant increase (p less than 0.001) in c-myc and beta-actin mRNA expression was observed, whereas FV mRNA expression appeared to be unchanged (p = 0.207). These inductions were transient, however, because by 15 or 24 h, beta-actin and c-myc expression levels, respectively, no longer exceeded those measured in untreated controls. However, in the presence of higher PMA doses (160 nM), beta-actin mRNA levels remained elevated at 24 h. The relationship between megakaryocyte maturation and apparent level of beta-actin mRNA expression was also examined. Although cell size and stage, and size and beta-actin mRNA levels showed a modest relationship, mRNA levels and morphologic maturation stage were poorly correlated. These results demonstrate that PMA has complex effects on gene expression in morphologically recognizable human megakaryocytes. Of equal importance, they also demonstrate that in situ hybridization can be employed as a useful tool for studying human megakaryocyte cell biology at the molecular level. PMID- 2201558 TI - A method to establish pure fibroblast and endothelial cell colony cultures from murine bone marrow. AB - Studies on the effect of the microenvironment on hematopoiesis would benefit from the availability of pure populations of nontransformed cells of each of the stromal cell types. The adherent murine bone marrow stromal cell population in this study consisted of fibroblasts, endothelial cells, and macrophages. Fibroblasts were segregated from the phagocytic endothelial cells and macrophages by allowing the phagocytic cells to ingest magnetic beads, with subsequent exposure to a magnetic field, effecting cell separation. Pure colony cultures of fibroblasts and endothelial cells were formed by varying the bead-to-cell ratio and incubation period of the cells. For complete purification of the fibroblasts, subsequent passaging was also necessary. Near confluent growth of each type was obtained with subsequent passages and sustained culture. The cytokine granulocyte macrophage colony-stimulating factor (GM-CSF) was used to enhance endothelial cell growth. We were not able to obtain pure populations of bone marrow macrophages in near confluent culture. The three cell types were identified by cellular morphology, acid and alkaline phosphatase staining, binding with the lectins Ulex europaeus and Bandeiraea simplicifolia, and the capacity to stain for the factor VIII-related antigen (von Willebrand's Factor). PMID- 2201559 TI - The role of hematopoietic growth factors in nuclear and radiation accidents. AB - Molecularly cloned hematopoietic growth factors are likely to be useful in treating persons with bone marrow failure resulting from radiation exposure. Some effects, such as increased granulocytes or platelets, are of clear therapeutic benefit. Other effects, such as a direct action on survival of hematopoietic stem cells and improved granulocyte function, may also increase survival. Many important areas remain to be studied, including which molecularly cloned hematopoietic growth factor(s) to use, optimal dose and timing, and others. Some of these issues can be studied in clinical trials; others require in vitro or animal models. Despite the limited data currently available, it is clear that the availability of molecularly cloned hematopoietic growth factors heralds a new era in treating radiation and nuclear accidents. PMID- 2201560 TI - Radiation induced blood pathology in chick-erythrocytes and related parameters. AB - White leghorn male chicks at 15 days post-hatching were subjected to acute (2.10 Gy and 6.60 Gy) and fractionated (2 x 2.10 Gy) whole body gamma radiation exposure at the high dose rate of 0.60 Gy/sec to study the nature of haematological changes induced in the animals which were maintained for a maximum period of 60 days post irradiation. The investigated parameters include total red blood cell counts, haemoglobin content, haematocrit value, mean corpuscular volume and mean corpuscular haemoglobin concentration values. The results show that the haematological changes induced with 2.10 Gy and 2 x 2.10 Gy fractionated dosage are reversible and do not cause permanent damage to the erythroid characteristics. However, the system failed to recover with 6.60 Gy whole body acute exposure. PMID- 2201561 TI - [New possibilities in searching for immunomodulators among compounds with a steroid structure]. AB - It was shown that a phytosteroid ecdisterone which is the principle of a new tonic drug ecdisten in doses of 5-20 mg/kg is able to stimulate the primary immune reaction slightly effecting the indices of T-cell immunity activity and phagocyte functions. On increasing ecdisterone dose to 50 mg/kg inhibition of the number of antibody cells in the mouse spleen was marked. PMID- 2201562 TI - [A new group of anti-arrhythmia agents (the search, results and concept)]. AB - The current status of the antiarrhythmic therapy is outlined: the main electrophysiological properties underlying the classifications of antiarrhythmic agents are presented; the principles of the search for new drugs are formulated. Using as an example the creation of a new group of antiarrhythmic agents, an attempt was made to develop the concept of the directed search for cardiotropic drugs among tricyclic nitrogen-containing systems. PMID- 2201563 TI - [The problems and outlook of geriatric pharmacology]. AB - The analysis of the molecular mechanisms underlying age-related changes in manifestations of pharmacokinetics, pharmacodynamics, therapeutic and toxic properties of drugs in the elderly is presented. The ways of their correction are discussed. The advances in the development of geriatric drugs (dekamevit, kvadevit, ampevit, orkomin, potassium glutaminate, rikavit, trimethylglycine) and the perspectives for the creation of new geroprotectors are described. PMID- 2201564 TI - [A first trial in the clinical study of bonnecor]. AB - The brief data on the results of the clinical trials of a new antiarrhythmic drug bonnecor at intravenous administration performed in six clinical institutions of the country are presented. A high effectiveness and a good tolerance of the drug in VT, VE, ST, SE and WPW syndrome were revealed. PMID- 2201565 TI - [Immunostimulants and autoimmunity]. AB - The review presents the recent data on the use of immunity stimulants (thymus peptides, synthetic immunomodulators, immunostimulants of bacterial origin) under conditions of experimental autoimmunity and in clinic. A brief characteristic of the immunotropic activity of the drugs is given, the mechanisms of their action on the formation of the autoimmune response and clinical effectiveness are analyzed. PMID- 2201567 TI - [The clinical pharmacology of drugs for the therapy of the broncho-obstructive syndrome]. AB - The pharmacodynamic and pharmacokinetic characteristics of different bronchodilators are presented. The principles of their rational combination with drugs of other groups are given. PMID- 2201566 TI - [Endogenous metabolites as modulators of the transport of drugs by serum albumin]. AB - The ability of serum albumin to bind reversibly on its surface drugs and to transport them in the process of distribution and elimination has been well established. Some endogenous metabolites, particularly unesterified fatty acids, bile acids, L-tryptophan and bilirubin which are formed both under physiological conditions and in pathological states of the organism, e.g., in uremia can displace drugs from their areas of binding on albumin molecule. The detection of endogenous metabolites and the study of the mechanism through which they displace drugs from the specific areas on plasma proteins is the urgent task of pharmacology. PMID- 2201568 TI - 2-Deoxy-D-glucose resistant yeast with altered sugar transport activity. AB - The transport of glucose and maltose in Saccharomyces cerevisiae was observed to occur by both high and low affinity transport systems. A spontaneously isolated 2 deoxy-D-glucose resistant mutant was observed to transport glucose and maltose only by the high affinity transport systems. Associated with this was an increase in the Vmax values, indicating derepression of the high affinity transport systems. The low affinity transport systems could not be detected. This mutant will be important in examining the repression regulatory and sugar transport mechanisms in yeast. PMID- 2201569 TI - Macrophage proteases can modify low density lipoproteins to increase their uptake by macrophages. AB - When low density lipoprotein (LDL) was incubated with sonicated macrophages at acidic pH, its protein moiety was partially degraded by cathepsins B and D. The reisolated LDL was taken up by intact macrophages up to about 20 times as fast as control LDL. LDL proteolysis and its enhanced uptake could be inhibited almost entirely by the selective protease inhibitors leupeptin and pepstatin. If macrophages in atherosclerotic lesions were to release acidic proteases (either by exocytosis or following cell death) and these were to modify LDL, this may help to explain why so much cholesteryl ester accumulates in these cells. PMID- 2201570 TI - Influence of the second and third codon on the expression of recombinant hirudin in E. coli. AB - The effect of all possible codons corresponding to the second and third amino acid (isoleucine and threonine) on the expression level of hirudin in E. coli has been analysed. These levels could not be correlated with changes in primary and secondary mRNA structure. A decrease in the rate of synthesis and of product accumulation follows the introduction for ile of the ATA codon which is of very low usage, and for thr of the ACC codon, which results in homology of the mRNA with the 3'-end of 16S rRNA. The results are discussed according to current concepts of protein expression in E. coli. PMID- 2201571 TI - Comparison of inhibitor binding in HIV-1 protease and in non-viral aspartic proteases: the role of the flap. AB - The crystal structure of HIV-1 protease with an inhibitor has been compared with the structures of non-viral aspartic proteases complexed with inhibitors. In the dimeric HIV-1 protease, two 4-stranded beta-sheets are formed by half of the inhibitor, residues 27-29, and the flap from each monomer. In the monomeric non viral enzyme the single flap does not form a beta-sheet with an inhibitor. The HIV-1 protease shows more interactions with a longer peptide inhibitor than are observed in non-viral aspartic protease-inhibitor complexes. This, and the large movement of the flaps, restricts the conformation of the protease cleavage sites in the retroviral polyprotein precursor. PMID- 2201572 TI - Light-induced D1-protein degradation in isolated photosystem II core complexes. AB - Photoinhibitory illumination of isolated oxygen evolving photosystem II core complexes results in a substantial degradation of the D1-protein which is accompanied by the appearance of high amounts of at least 4 different degradation products. It is suggested that the degradation is due to a protease that is an integral part of the photosystem II complex. PMID- 2201573 TI - The Saccharomyces cerevisiae CDC25 gene product is a 180 kDa polypeptide and is associated with a membrane fraction. AB - In the yeast Saccharomyces cerevisiae, the CDC25 gene product is supposed to interact with ras proteins and adenylate cyclase for progression through the cell division cycle. To identify the CDC25 gene product, we raised antibodies against two hybrid proteins, encoded by in-frame fusions between the E. coli lacZ gene and two different parts of the CDC25 gene. By protein immuno-blotting, we were able to identify the CDC25 gene product as a 180 kDa polypeptide, which we named p180CDC25. It was detected only when the CDC25 gene was overexpressed in a proteases-deficient yeast strain. Subcellular fractionation experiments showed that p180CDC25, as well as ras proteins, is attached to the membrane, even after treatments which release peripheral membrane proteins. PMID- 2201574 TI - SecE-dependent overproduction of SecY in Escherichia coli. Evidence for interaction between two components of the secretory machinery. AB - The secY and secE genes were individually cloned and placed under the control of the tac promoter on plasmids. Induction with isopropyl-beta-D thiogalactopyranoside resulted in the overproduction of SecE, but not that of SecY. The simultaneous induced expression of both genes in the same cells resulted in the overproduction of SecY together with that of SecE. SecY and SecE thus overproduced were localized in the cytoplasmic membrane as those expressed at the normal levels were. It is suggested that SecY and SecE interact with each other in the cytoplasmic membrane. The numbers of the SecY and SecE molecules per cell were estimated. PMID- 2201575 TI - [Numerical anomalies of the dentition with respect to various types of teeth. 2. (Molars and multiple anomalies). Dentition anomalies among cases of a district dentist, 7]. AB - The significance of the numerical anomalies of the teeth is seen for the general medical science that it may be helpful for solving of questions raised by other hereditary anomalies. This report deals with the numerical anomalies of the molars, and it reports the variety of the multiple numerical anomalies. The latters may appear very multifarously and may occur extremities (complete edentulousness and jaw bone doubling, respectively), too. PMID- 2201576 TI - [Roles of the kidney in activation and release of plasma inactive renin in the rat]. AB - Plasma inactive as well as active renin is supposed to originate from the kidney, though there is little direct evidence. As we have previously reported (Sakanaka et al., Folia Endocrinol. Jap., 63: 961-977, 1987; Miyazaki et al., J. Hypertension 4 (Suppl 6): S453-S455, 1986; Miyazaki et al., J. Hypertension 6: 33 40, 1988), the submandibular gland, but not the kidney, is thought to play an crucial role in releasing plasma inactive renin in the rat. In the present acute studies, we attempted to elucidate the roles of the kidney in the release mechanisms of plasma inactive renin. Adult male rats maintained on a regular rat chow (Na: 260 mg/100g) were uninephrectomized, and vessel clips were placed on the renal pedicles of the contralateral kidneys to make completely ischemic and non-filtered kidneys. In the first protocol, the renal pedicles were occluded for 2 h, followed by the removal of the vessel clips. During the occlusion for 2 h, plasma active renin concentration (PAC) in the peripheral blood obtained from the femoral cannulae decreased, while plasma inactive renin concentration (PIC) along with plasma total renin concentration (PTC) increased as in the case of total nephrectomy, which supports our previous studies. Then, declipping resulted in the rapid rise in PAC with the peak values at 2 min, which was followed by its gradual decrease with time during the experimental period (30 min). On the other hand, PIC decreased gradually toward control levels with no rise after declipping. In the second protocol, blood trapped in the kidney was collected through the renal venous cannulae at 0, 60, 120 and 240 min after the pedicle occlusion in the different groups of rats. The renal blood levels of PAC increased by more than three times at 240 min compared to the control values, while PIC decreased to one third of the control values. PTC increased at 120 and 240 min. Renal tissue levels of renin were also measured at 0 and 120 min in the second protocol in the kidneys of rats which were maintained on a regular rat chow. Inactive renin concentration increased, while active renin concentration decreased. These were compatible with the results obtained in plasma. In the last protocol, the second protocol was in part repeated in salt-depleted rats which were kept on a low salt diet (Na: 11.3 mg/100g) for 2 weeks.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2201577 TI - Diagnostic outcome and observer performance in sagittal tomography of the temporomandibular joint. AB - The diagnostic outcome and observer performance of sagittal tomography in detecting degenerative lesions of the temporomandibular joint was studied. Thirty tomograms depicting findings such as cyst, erosion, osteophyte and sclerosis and 30 with a normal appearance were selected. The joint status was verified histologically. Four observers evaluated the tomograms with the aid of reference tomograms, independent of the microscopic examination. The diagnostic accuracy was high (80-87%). The sensitivity was between 67% and 90% and the specificity between 73% and 93%. An osteophyte was, with few exceptions, a true finding whereas sclerosis most frequently was false. About two-thirds of the reports of cyst and erosion were found to be true. The interobserver overall agreement rates for any two observers varied between 68% and 90%, for three observers between 65% and 82%, and for all four observers was 63%. The Kappa value for any two observers was 0.40-0.80, indicating fair to substantial agreement. The intra observer agreement was only somewhat higher than the interobserver. This study shows that, with the aid of reference tomograms, high diagnostic accuracy and observer agreement can be achieved in sagittal tomography. PMID- 2201578 TI - Ultrasonic diagnosis of masseteric hypertrophy. AB - Masseteric hypertrophy may present a diagnostic dilemma, its confirmation frequently being by exclusion of other conditions. The literature relating to this syndrome is reviewed. A study to confirm the suitability of ultrasound in diagnosis, and to establish a normal range, is described. Sixty-two masseter muscles were measured using a standardized technique and the derived normal range for transverse dimension was 8.5-13.5 mm. Three instances of clinically diagnosed masseteric hypertrophy were examined; in each case measured transverse masseteric dimension was significantly greater than the normal range. Direct ultrasonic measurement of masseteric bulk should replace computed tomography as the definitive investigation in suspected cases. PMID- 2201579 TI - Comparison of computed with conventional tomography in the evaluation of temporomandibular joint disease: a study of autopsy specimens. AB - Autopsy specimens were examined both radiographically and macroscopically to compare direct computed tomography (CT) with conventional tomography (CVT) for their diagnostic yield of the structural bone changes in the temporomandibular joint (TMJ). Fifteen specimens were examined with corrected sagittal and 12 with corrected frontal tomography. Five joints showed bone exposure and/or disc perforation macroscopically and all of them were correctly diagnosed by both CT and CVT (sensitivity 1.0). However, false-positive diagnoses were also made, resulting in values for specificity which were somewhat lower for CT than for CVT. Frontal images did not reveal any additional 'true' findings compared with sagittal CT or CVT. For single areas of the joints the average sensitivity was low, 0.28 for CT and 0.47 for CVT, but the specificity for the joint as a whole was high with both methods (0.91 and 0.94 respectively). We conclude that CVT is superior to CT in the diagnosis of single structural bone changes but comparable for comprehensive diagnosis of TMJ disease. PMID- 2201580 TI - Transcriptional regulation of actin and myosin genes during differentiation of a mouse muscle cell line. AB - During terminal differentiation of skeletal muscle cells in vitro there is a transition from a predominantly nonmuscle contractile protein phenotype to a sarcomeric contractile protein phenotype. In order to investigate whether this transition and subsequent changes in expression are primarily transcriptionally regulated, we have analysed the rate of transcription and level of corresponding RNA accumulation of actin and myosin light chain genes during differentiation of a mouse muscle cell line under different culture conditions (low-serum and serum free). We have found by 'nuclear run-on' analysis, that the alpha-cardiac actin, alpha-skeletal actin, myosin light chain 1F/3F and embryonic myosin light chain genes are transcriptionally activated as myoblasts begin to fuse to form myotubes. In contrast the nonsarcomeric beta-actin gene is transcribed at high levels in myoblasts and is transcriptionally down-regulated during differentiation. There is a sequential transition in transcription and RNA accumulation from predominantly alpha-cardiac to predominantly alpha-skeletal actin during subsequent myotube maturation, which reflects the pattern of expression found during development in vivo. A similar transition from embryonic to adult patterns of myosin light chain expression does not occur. RNA accumulation of actin and myosin light chains is regulated at both transcriptional and post-transcriptional levels. In our culture system the expression of myosin light chains 1F and 3F, which are encoded by a single gene, is uncoupled, 3F predominating. These data are discussed in the context of gene regulation mechanisms. PMID- 2201581 TI - [Polycystic ovary syndrome: a hypothalamic or a gonadal anomaly?]. AB - Evidence obtained from the study of polycystic ovarian disease in the female is reviewed. The etiology of this problem remains unknown, in spite of advances achieved by means of biochemical and morphologic studies. No correlation has been observed between histological findings and the pituitary or gonadal hormone production. However, an abnormal hypothalamic-pituitary-gonadal interaction prevails, characterized by a increased LH-FSH ratio associated with high level of androgens, mainly androstenedione. The pituitary reserve test performed with potent GnRH agonists have confirmed the hyper-response of LH along with that of androstenedione, as well as augmentation of 17-hydroxyprogesterone. Since the pattern of gonadotropins and steroid hormone secretion in women with polycystic ovarian disease resembles that seen in normal men, the basic alteration may well consist in a functionally "masculinized" hypothalamus. PMID- 2201582 TI - [Animal experimentation and its repercussion on human health]. PMID- 2201583 TI - Binding of proteolytically-degraded human colonic mucin glycoproteins to the Gal/GalNAc adherence lectin of Entamoeba histolytica. AB - Rat and human colonic mucin glycoproteins bind to the Gal/GalNAc adherence lectin on the surface of Entamoeba histolytica in vitro, thus inhibiting the organism from adhering to and lysing the target cells. Human colonic mucin glycoproteins were isolated by Sepharose 4B gel filtration chromatography, they were proteolytically degraded with trypsin, pronase, and papain, and the glycoprotein fractions were reisolated by Sephacryl S-200 gel filtration chromatography. Binding of the mucin glycoprotein fractions to amoebae was quantitated by the inhibition of adherence of Chinese hamster ovary cells to the surface of the amoebae. Trypsin and papain digests caused 40 and 20% reductions, respectively, in the excluded fractions (void volume) that contained all the carbohydrates; pronase digests resulted in extensive degradation of the mucin glycoprotein with the carbohydrate fractions eluting over 40% of the gel bed volume. 3H-labelled mucin glycoprotein and sodium dodecylsulfate-polyacrylamide gel electrophoresis confirmed the presence of the high molecular weight carbohydrate-rich glycoproteins with no subunits in the excluded fractions and the absence of sugars in the included peptides. Only the high molecular weight carbohydrate containing fractions bind amoebae and inhibit amoebic adherence to Chinese hamster ovary cells. The trypsin digested mucins in the excluded volume were more efficient than the native undigested mucins in binding amoebae. The carbohydrate containing fractions of the pronase digests were the least effective in binding amoebae and inhibiting adherence of Chinese hamster ovary cells. This suggests that proteolytically-degraded colonic mucins that are glycosylated, as well as the undegraded native mucin glycoproteins of the gut, may play a protective role in binding to amoebae, thus preventing contact of amoebae with mucosal epithelial cells and potential invasion. PMID- 2201584 TI - Caerulein induced plasma amino acid decrease: a simple, sensitive, and specific test of pancreatic function. AB - We measured total plasma amino acid concentrations before and during pancreatic stimulation with secretin (1 clinical unit/kg/h) and caerulein (50 ng/kg/h) in 28 healthy volunteers, 60 patients with chronic pancreatitis (25 mild to moderate, 35 severe), and 22 patients with non-pancreatic digestive disease. In the healthy volunteers and patients with non-pancreatic digestive disease pancreatic stimulation caused a significant decrease (p less than 0.001) in plasma amino acid concentration, whereas in patients with chronic pancreatitis the decrease did not occur or was only slight. In six healthy volunteers and 24 patients with chronic pancreatitis (nine mild to moderate, 15 severe) repetition of the test using caerulein alone showed no significant differences from combined stimulation. Using the maximal per cent decrease in plasma amino acid concentration as an index of pancreatic function (lower normal limit 14%), 20 of the 25 patients with mild to moderate pancreatitis (80%) and 32 of the 35 with severe pancreatitis (91.4%) had values clearly below normal. The overall sensitivity of the test (86.7%) was significantly greater than that of the pancreolauryl test (64.2%) (p less than 0.02) and that of faecal chymotrypsin (66%) (p less than 0.05). None of the patients with non-pancreatic digestive disease had abnormal values. We conclude that the assessment of the decrease in the plasma amino acid concentration during pancreatic stimulation with secretin and caerulein is a simple, sensitive, and highly specific test of pancreatic function. The data obtained using caerulein stimulation alone suggest that the test can be further simplified, and made less costly, by eliminating the use of secretin. PMID- 2201585 TI - Ultrasonically guided histological and cytological fine needle biopsies of the pancreas. Reliability and reproducibility of diagnoses. AB - In 100 consecutive patients ultrasonically guided histological and cytological fine needle biopsy specimens were obtained from pancreatic lesions using two different needles with an outer diameter of 0.6 mm. Specimens taken by both cytological and histological fine needle biopsy were examined blindly by two pathologists. When related to the final and reliable diagnosis obtained in 57 patients, the predictive value of a malignant diagnosis was 1.00 for both types of biopsy. The predictive value for a benign diagnosis was 0.25 for histological specimens for both examiners and 0.33 and 0.45 for the two evaluations of the cytological specimens. False benign diagnoses seemed to be related to both sampling error and difficulties in interpreting the biopsy specimens. The intraobserver and interobserver kappa values concerning reproducibility of diagnoses were higher for histological specimens (0.80 and 0.74) than for cytological specimens (0.70 and 0.61). Consistent malignant diagnoses, however, occurred more often with cytological specimens (51 cases) than with histological specimens (39 cases) (p less than 0.05) and consistent diagnoses of insufficient material were more common with histological specimens (18 cases v six cases). Cytological fine needle biopsy seems to be the method of choice if only one method is used and a 0.6 mm needle is used. PMID- 2201587 TI - Primary paraovarian cystadenocarcinoma: clinical and management aspects and literature review. AB - Two cases of primary paraovarian-origin serous cystadenocarcinoma, one invasive and one of low malignant potential, are presented. Both were diagnosed in postmenopausal women and were initially treated surgically. As of this writing, both women have survived 48 months past their initial diagnosis and have no clinically detectable disease. Clinical aspects and management problems of this fairly recently identified and rare entity are discussed and the literature on primary paraovarian malignant epithelial tumors is reviewed. PMID- 2201588 TI - [Doppler ultrasound. Introduction to the topic]. PMID- 2201586 TI - Helicobacter pylori: bridging the credibility gap. AB - In summary, therefore, there are interesting associations between H pylori, duodenal ulcer, and non-ulcer dyspepsia. In type B gastritis there may be enough evidence to suggest a causal role. The relation between gastritis and upper gastrointestinal symptomatology, however, remains contentious. The relation between H pylori and acid secretion may be more intimate than was previously thought. 'Pylorites' must temper their enthusiasm and provide hard data; 'Schwartzians' must broaden their horizons. PMID- 2201590 TI - [Terminology in obstetric Doppler studies]. PMID- 2201589 TI - [12 years of Doppler ultrasound in gynecology and obstetrics: retrospect and prospects]. PMID- 2201591 TI - [Doppler ultrasound studies in obstetrics]. PMID- 2201592 TI - [Gynecologic Doppler flow measurements]. PMID- 2201594 TI - [Value of the aortic/carotid ratio for predicting increased fetal acidosis]. PMID- 2201593 TI - [New diagnosis of abnormal uterine perfusion using transvaginal Doppler flow measurement of both uterine arteries]. PMID- 2201595 TI - [Diastolic flow compromise in the umbilical artery and fetal aorta; correlation of cardiotocography and neonatal status]. PMID- 2201596 TI - [Immunodiagnosis and its relevance in neoplastic disease, immunotherapy in neoplastic disease]. PMID- 2201597 TI - [Immunological aspects in recurrent infections in gynecology]. PMID- 2201598 TI - [Immunological aspects of endometriosis]. PMID- 2201599 TI - [Reproduction immunology]. PMID- 2201600 TI - [Immunologically-induced sterility with reference to female and male factors]. PMID- 2201601 TI - [Immunomodulation in early pregnancy]. PMID- 2201602 TI - [Prevention of habitual abortion using intravenously administered polyvalent immunoglobulins]. PMID- 2201603 TI - [Findings and hypotheses in the immunological etiology of gestosis and intrauterine fetal growth retardation]. PMID- 2201604 TI - [Therapy with antithrombin III concentrate]. PMID- 2201607 TI - [Pulmonary manifestations of AIDS]. PMID- 2201605 TI - [Preliminary study for the evaluation of the feasibility of a multicenter clinical trial for the evaluation of the therapeutic efficacy of an antithrombin III concentration (Immuno) in the intravascular coagulation syndrome]. PMID- 2201609 TI - [Advances in genetics of retinoblastoma]. PMID- 2201608 TI - [Musculoskeletal manifestations of human immunodeficiency virus infection]. PMID- 2201606 TI - [Congenital deficiency of antithrombin III]. PMID- 2201611 TI - [Tissue expanders--a new reconstructive aid]. PMID- 2201610 TI - [Bulimia nervosa]. PMID- 2201612 TI - [Drug-induced pulmonary diseases]. PMID- 2201613 TI - [The impaired physician]. PMID- 2201614 TI - [Pathophysiology of intestinal obstruction: innovations]. PMID- 2201615 TI - [Modern approach to evaluation, treatment and follow-up of hypertensive patients]. PMID- 2201616 TI - [Introduction to electrocardiographic surface recordings of late cardiac potentials]. PMID- 2201617 TI - [Hyperinsulinism and hyperandrogenism in polycystic ovarian disease]. PMID- 2201618 TI - [Pseudocyesis]. PMID- 2201619 TI - [Ureaplasma urealytic and neonatal morbidity]. PMID- 2201620 TI - [Giardia lamblia infection: laboratory and clinical aspects]. PMID- 2201622 TI - Prediction of the conformation of D1/D2 heterodimer of photosynthetic reaction centre II using a modified Chou-Fasman method. AB - Chou-Fasman method was modified to account for amphipathic nature of Gly and hydrophobic environment. The modified method shows improvement in prediction accuracy from 35 to 70% and can be applied to predict the conformation of D1, D2 polypeptides of reaction centre II of thylakoid, which are analogous to L and M respectively. Possible sites for Mn binding to D1/D2 heterodimer are postulated. PMID- 2201623 TI - Changes in thyroid hormone and insulin status of the brown adipose tissue of cold acclimated rats on short term exposure to heat. AB - Acclimation of rats to cold caused 45% increase in the concentration of triidothyronine (T3) and 35% increase in the concentration of thyroxine (T4) in serum. Exposure of cold-acclimated rats to heat (12 hr, 37 degrees C) failed to decrease the concentrations of thyroid hormones in circulation. The concentration of T3 in brown adipose tissue (BAT) increased almost 10-fold on cold acclimation. Iodothyronine deiodinase activity also registered 3-fold increase. Exposure of cold-acclimated animals to heat caused decrease in the concentration of T3 in BAT without appreciably affecting T4 concentration. In liver tissue, the changes in hormone concentrations were quite small compared to those in BAT. On thyroidectomy or when fed with propyl thiouracil, rats could not survive exposure to the cold. The concentration of insulin in circulation showed small increase, while that in the tissues showed significant decrease on acclimation of rats to the cold. The concentration of the hormone in BAT registered significant increase on exposure of cold-acclimated animals to heat (12 hr, 37 degrees C). The increase in liver was marginal. The temperature-dependent response of T3 indicates an important role for this hormone in rapid physiological response in BAT. PMID- 2201621 TI - [Smoking and pregnancy]. PMID- 2201624 TI - Diagnosis of acanthamoeba keratitis--a report of four cases and review of literature. AB - Acanthamoeba keratitis is not reported often in India. We reported the first case diagnosed in this country a year back. In this communication, four more cases of Acanthamoeba keratitis diagnosed since then are being reported along with a brief review of literature. Diagnosis in all these patients was based on observation of acanthamoeba cysts in 10% KOH wet mount of corneal ulcer scrapings and subsequent culture. The characteristic ring infiltration of cornea was seen in all of them. All cases were treated medically with the available antiamoebic drugs (Miconazole, Neosporin, Ketoconazole and Metronidazole) in different combinations. Only one out of four, responded with complete healing of the ulcer. Acanthamoeba keratitis is probably not as uncommon in India as it is thought to be. With increased awareness and performance of minimal laboratory tests the condition may be diagnosed more often. PMID- 2201625 TI - SAFA test as an aid to the diagnosis of ocular tuberculosis. AB - A prospective double blind study was carried out to evaluate the role of soluble antigen fluorescent antibody (SAFA) test to detect ocular Tuberculosis. The study material comprised 39 patients with suspected ocular tuberculosis suffering from interstitial keratitis, sclero keratitis, granulomatous uveitis, phlyctenular keratoconjunctivitis, Eales disease and central serous retinopathy. The cases of proven ocular tuberculosis showed up as 70 percent strong reactors and 30 percent weak reactors to SAFA while none had a negative response to SAFA. Of these cases skin hypersensitivity reaction was positive only in 40 percent of the cases. The control group revealed a strong SAFA reaction in only 4 percent of cases with a weak reaction in 44 percent of cases. It thus appears that SAFA test can provide a useful addition to the routine tests in diagnosing tuberculosis. PMID- 2201626 TI - Skin grafting in severely contracted socket with the use of 'Compo'. AB - The results of split thickness autologous skin grafting along with the use of a dental impression material (Compo), a thermoplastic substance are presented in a series of 11 patients of acquired, severely contracted, anophthalmic sockets. Only the fornix fixation sutures and the central tarsorrhaphy were employed for the proper placement of graft without the use of retention devices. Artificial eyes were successfully fitted and retained subsequently after 6 weeks of grafting. PMID- 2201627 TI - Live male adult W. bancrofti in the anterior chamber--a case report. PMID- 2201628 TI - [Bond in orthodontics. Study of the bond as a function of time and brushing technic]. PMID- 2201629 TI - [Overlay dentures with "push button" type axial attachments. Use of isolated roots for retention of overlay dentures]. PMID- 2201630 TI - [Bacterial penetration: a major role in the pathogenesis of periodontal disease?]. PMID- 2201631 TI - [1989 guide to the dentistry market--Tokyo in the race to bid!]. PMID- 2201632 TI - [Second generation amalgam. In vitro study and multicenter survey]. PMID- 2201634 TI - [Use of lyophilized decalcified bone in filling periodontal lesions]. PMID- 2201633 TI - [Overlay dentures. Conservation of roots without attachments]. PMID- 2201635 TI - [Factors influencing the prognosis of completely built transplanted teeth]. PMID- 2201636 TI - [Immediate complete denture. Model adjustment, surgical stage and denture placement]. PMID- 2201637 TI - Tumor necrosis factor (TNF) is induced in mice by Candida albicans: role of TNF in fibrinogen increase. AB - One intraperitoneal dose of Candida albicans (10(8) CFU) caused a chronic (longer than 2 months), significant elevation of plasma fibrinogen levels (Clauss method) in mice of strain C3H/HeN. Even a small dose (10(6) CFU) resulted in a significant increase in fibrinogen level for 5 days following injection, whereas other blood parameters (leukocytes, erythrocytes, platelets, hematocrit, hemoglobin, blood urea nitrogen, aspartate aminotransferase, albumin, alkaline phosphatase, antithrombin III, glucose, calcium, and total protein) measured by standard methods were normal. Blood taken during this period was negative for C. albicans. The role of tumor necrosis factor (TNF) in C. albicans infections was investigated by measuring the fibrinogen response after the administration of C. albicans or recombinant mouse TNF-alpha. Both challenges resulted in an elevated fibrinogen level. When polyclonal antibodies to mouse TNF-alpha were given prior to challenge with C. albicans or mouse TNF-alpha, the fibrinogen increase was significantly inhibited. C. albicans injections were found to significantly elevate endogenous TNF levels in mice (enzyme-linked immunosorbent assay). It was concluded that C. albicans induces TNF in the mouse. Furthermore, these data give evidence which supports a relationship between TNF and the fibrinogen increase induced by C. albicans. PMID- 2201638 TI - Two soluble antigens of Plasmodium falciparum induce tumor necrosis factor release from macrophages. AB - The production of cytokines such as tumor necrosis factor (TNF) may contribute to the pathology of malaria. We showed previously that crude preparations of heat stable exoantigens from parasite cultures induce the release of TNF in vitro and in vivo. When separated from the culture medium by affinity chromatography, in which immune immunoglobulin G was used as ligand, the mixture of exoantigens of Plasmodium falciparum retained the capacity to induce the secretion of TNF, both by human monocytes from Gambian children and by mouse macrophages. Two individual antigens, Ag1 and Ag7, further purified by affinity chromatography and identified by crossed immunoelectrophoresis, also stimulated TNF production by both types of cell but differed in other functional properties. Thus, the activity of Ag7, but not that of Ag1, was inhibited by polymyxin B, and antisera made against boiled exoantigens of the rodent parasite Plasmodium yoelii which blocked the ability of these antigens to induce the production of TNF also inhibited the activity of Ag7 without affecting Ag1. Since the prevalence of antibody against Ag7 in sera from children in endemic areas appears to correlate with the development of immunity against the manifestations of the disease, this antigen may be one cause of pathology, perhaps through its ability to induce the production of TNF. Its serological relationship with rodent exoantigens suggests that it might be a candidate for an anti-disease vaccine which has the advantage that its active moiety is not subject to significant antigen polymorphism. PMID- 2201639 TI - Cloning, expression, and occurrence of the Brucella Cu-Zn superoxide dismutase. AB - Recently, the complete amino acid sequence of a protein expressed in Escherichia coli from cloned Brucella abortus DNA was reported. On the basis of amino acid homology, this protein was identified as a copper-zinc superoxide dismutase (Cu Zn SOD) (B. L. Beck, L. B. Tabatabai, and J. E. Mayfield, Biochemistry 29:372 376, 1990). We demonstrate in this paper that the sequenced protein is the same as the previously studied salt-extractable protein BCSP20. The plasmid-encoded protein expressed from recombinant E. coli is identical to the Brucella-derived BCSP20 in molecular mass, N-terminal amino acid sequence, and cross-reactivity with homologous and heterologous rabbit sera against either the recombinant gene product or the Brucella-derived protein. A survey of the expression of the Cu-Zn SOD protein in Brucella biovars representing all species was done by Western blotting (immunoblotting) using antisera raised against the recombinant E. coli derived protein. With the exception of B. neotomae and B. suis biovar 2, the Cu Zn SOD protein was detectable in all Brucella species and biovars tested, including eight biovars of B. abortus. PMID- 2201640 TI - Neither motility nor chemotaxis plays a role in the ability of Escherichia coli F 18 to colonize the streptomycin-treated mouse large intestine. AB - Escherichia coli F-18, isolated from the feces of a healthy human in 1977, is an excellent colonizer of the streptomycin-treated mouse large intestine and displays normal motility and chemotaxis ability. A chemotaxis-defective derivative of E. coli F-18, E, coli F-18 CheA-, and a nonflagellated derivative, E. coli F-18 Fla-, were constructed. These strains were found to colonize the streptomycin-treated mouse large intestine as well as E. coli F-18 when mice were fed both E. coli F-18 and either the CheA- or Fla- derivative at high levels (10(10) CFU of each strain per mouse) or low levels (10(4) CFU of each strain per mouse). Furthermore, E. coli F-18 lost motility and chemotaxis ability when grown in colonic or cecal mucus in vitro despite retaining the ability to synthesize flagella. Thus, it appears that neither motility nor chemotaxis plays a role in the ability of E. coli F-18 to colonize because this strain becomes functionally nonmotile upon growth in the streptomycin-treated mouse large intestine. PMID- 2201642 TI - Nucleotide sequence of yst, the Yersinia enterocolitica gene encoding the heat stable enterotoxin, and prevalence of the gene among pathogenic and nonpathogenic yersiniae. AB - The gene encoding the heat-stable enterotoxin (yst) was cloned from the chromosome of Yersinia enterocolitica W1024 (serotype O:9), and the nucleotide sequence was determined. The yst gene encodes a 71-amino-acid polypeptide. The C terminal 30 amino acids of the predicted protein exactly correspond to the amino acid sequence of the toxin extracted from culture supernatants (T. Takao, N. Tominaga, and Y. Shimonishi, Biochem. Biophys. Res. Commun. 125:845-851, 1984). The N-terminal 18 amino acids have the properties of a signal sequence. The central 22 residues are removed during or after the secretion process. This organization in three domains (Pre, Pro, and mature Yst) resembles that of the enterotoxin STa of Escherichia coli. The degree of conservation between the E. coli and Y. enterocolitica toxins is much lower in the Pre and the Pro domains than in the mature proteins. The mature toxin of Y. enterocolitica is much larger than that of E. coli, but the active domain appears to be highly conserved. The yst gene of Y. enterocolitica introduced in E. coli K-12 directed the secretion of an active toxin. The cloned yst gene was used as an epidemiological probe among a collection of 174 strains representative of all Yersinia species except Yersinia pestis and numerous Y. enterocolitica subgroups. In Y. enterocolitica, there was a clear-cut difference between pathogenic and nonpathogenic strains: 89 of 89 pathogenic and none of 51 nonpathogenic strains contained yst-homologous DNA, suggesting that Yst is involved in pathogenesis. Among the other Yersinia species, only four strains of Yersinia kristensenii had DNA homologous to yst. PMID- 2201641 TI - A system for production and rapid purification of large amounts of the Shiga toxin/Shiga-like toxin I B subunit. AB - We have constructed a plasmid expression vector (pSBC32) that encodes the B subunit of Shiga toxin/Shiga-like toxin I under control of the inducible trc promoter. The encoded B subunit is transported to the periplasmic space, allowing single-step purification of milligram amounts of this protein from periplasmic extracts by using receptor analog affinity chromatography. The purified B subunit interacts normally with both polyclonal antiserum to Shiga toxin and a monoclonal antibody specific for B subunit. B subunit purified in this system is pentameric (as in native holotoxin) and biologically active in blocking binding of Shiga holotoxin to HeLa cells. This expression system may allow rapid purification of sufficient amounts of Shiga toxin B subunit to attempt crystallization or to study its efficacy as a vaccine, either by itself or coupled to an appropriate polysaccharide antigen. PMID- 2201643 TI - Bacterial infection of wounds: fibronectin-mediated adherence group A and C streptococci to fibrin thrombi in vitro. AB - Adherence of group A, B, and C streptococci to fibrin thrombi was studied by using a novel fluorochrome microassay carried out in microdilution plates in which fibrin thrombi had been prepared by clotting citrated human, cattle, or horse plasma. Substantial adherence was observed with various strains of group A and C streptococci, whereas little was observed with group B streptococci. Adherence of all group A and C streptococcal strains decreased by up to 40% when fibronectin was depleted from the plasmas used for preparing fibrin thrombi, and fibronectin repletion increased adherence of streptococci in a dose-dependent manner. Addition of the 210-kilodalton C-terminal fragment of fibronectin to fibronectin-depleted plasma restored the adherence of group C but not group A streptococci, whereas addition of the 29-kilodalton N-terminal fragment was without any effect for all tested streptococcal strains. Prior incubation of group A and C streptococcal strains with fibronectin markedly increased their adherence, but treatment with proteases abolished their ability to adhere to fibrin thrombi. Adherence of group B streptococci was not affected by either fibronectin depletion or proteolytic digestion. These results indicate that both fibronectin incorporated into the fibrin matrix of thrombi and soluble fibronectin can mediate adherence of group A and C streptococci to fibrin thrombi and that binding sites for fibronectin located on the bacterial surface mediate this adherence. PMID- 2201644 TI - Secretory immunoglobulin A carries oligosaccharide receptors for Escherichia coli type 1 fimbrial lectin. AB - Type 1 fimbriae with mannose-specific lectins are widely distributed among members of the family Enterobacteriaceae and confer the ability to attach to a range of host cells, including colonic epithelial cells. The mucosal surfaces are protected by secretory immunoglobulin A (IgA), which agglutinates microorganisms and prevents their attachment to host epithelial cells. This action has been attributed to a specificity of the antigen-combining site of mucosal immunoglobulins for bacterial and viral surface components. Here, we report a novel mechanism for the antibacterial effect of secretory IgA. Secretory IgA and IgA myeloma proteins, especially those of the IgA2 subclass, were shown to possess carbohydrate receptors for the mannose-specific lectin of type 1 fimbriated Escherichia coli. The presence of the high-mannose oligosaccharide chain Man alpha 1-6(Man alpha 1-3)Man alpha 1-6(Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc correlated with binding activity. The interaction between bacterial mannose-specific lectins and IgA receptor oligosaccharide resulted in agglutination of the bacteria and in inhibition of bacterial attachment to colonic epithelial cells. Thus, this interaction could form the basis for a broad antibacterial function of secretory IgA against enterobacteria regardless of the specificity of antibody molecules. PMID- 2201645 TI - Characterization of Tritrichomonas foetus antigens by use of monoclonal antibodies. AB - The specificity for and function of monoclonal antibodies against Tritrichomonas foetus were characterized. Four monoclonal antibodies generated by immunization of mice with live T. foetus were selected on the basis of enzyme-linked immunosorbent assay reactions. The approximate molecular masses of the predominant proteins were determined by Western blotting (immunoblotting). Monoclonal antibody TF3.8 recognized a predominant band at approximately 155 kilodaltons, whereas TF3.2 reacted with several bands. Monoclonal antibodies TF1.17 and TF1.15 recognized broad bands between 45 and 75 kilodaltons. The first two antibodies (TF3.8 and TF3.2) did not react with the surface of T. foetus, as determined by live-cell immunofluorescence, agglutination, and immobilization, whereas two other monoclonal antibodies (TF1.17 and TF1.15) did react with surface epitopes, as determined by these criteria. The latter two monoclonal antibodies also mediated complement-dependent killing of T. foetus and prevented of adherence of organisms to bovine vaginal epithelial cells. One antibody, TF1.15, also killed in the absence of complement. Since these functions are in vitro correlates of protection, the antigens recognized by these monoclonal antibodies may induce protective immunity. PMID- 2201646 TI - Experimental model of type IV Streptococcus agalactiae (group B streptococcus) infection in mice with early development of septic arthritis. AB - We have established an experimental murine model to gain insight into the pathogenicity and clinical features of type IV group B streptococcus (GBS) infections. Adult CD-1 mice were challenged intravenously with 10(7) type IV GBS cells, inducing systemic invasion. Most of the animals were able to clear the infection from the blood, brain, and lungs within 2 weeks and from the spleen and liver within 1 month. However, the animals were unable to clear the microorganism from the joints and kidneys during the 60-day observation period. About 80% of the mice challenged intravenously with type IV GBS manifested early septic arthritis, which evolved from an acute exudative synovitis to permanent lesions characterized by irreversible joint damage and ankylosis. Induction of persistent septic arthritis was dependent on the number and viability of microorganisms inoculated and was unrelated to the strain of type IV GBS and the growth phase of the inoculum. Type-specific antibodies of both immunoglobulin M and G classes could be detected by agglutination and enzyme-linked immunosorbent assay from days 7 and 14, respectively; immunoglobulin G antibodies persisted for more than 40 days. Complexes of antibodies and group- and type-specific antigens were detected in mouse sera 24 h after infection and persisted up to day 22. These results were obtained an experimental model of type IV GBS chronic infection with early development of septic arthritis, which could be useful in future studies of pathogenicity and immune mechanisms involved in the host resistance to this microorganism. PMID- 2201647 TI - Monoclonal antibodies demonstrate that superoxide dismutase contributes to protection of Nocardia asteroides within the intact host. AB - The importance of superoxide dismutase (SOD) in protecting cells of Nocardia asteroides from the oxidative killing mechanisms within the intact murine host was determined. Murine monoclonal antibodies specific for nocardial SOD and for another nocardial antigen were prepared. Both antibodies adhered to cell surface antigens, as shown by fluorescence-labeled-antibody staining. The anti-nocardial SOD antibody inhibited the effect of nocardial SOD on superoxide generated in vitro. Cells of N. asteroides GUH-2 in log phase of growth were incubated with monoclonal anti-nocardial SOD, another monoclonal antinocardial antibody (not reactive with SOD), or phosphate-buffered saline and then injected intravenously into mice. Total recovery of CFU and inhibition of growth were determined at 3, 24, and 48 h after infection. The brains, kidneys, spleens, lungs, and livers were weighed, homogenized, and plated in order to quantitate the number of organisms in each organ at each time period. There was an initial killing followed by enhanced clearance of N. asteroides from the lungs and livers of mice which had received anti-SOD antibody-treated nocardiae. There was also enhanced early killing in the spleen. At 48 h, there were fewer organisms recovered from the brains, kidneys, and livers of mice which had received anti-SOD antibody treated nocardia. This was not true for mice which had received antinocardial antibody not specific for SOD. The data demonstrate that surface-associated SOD protects N. asteroides for oxidative killing in vivo during all stages of infection. PMID- 2201649 TI - Measurement of testicular volume by ultrasonography. AB - To measure testicular volume accurately, an ultrasonographic method was developed and the results obtained from this compared with those obtained by conventional measurements, namely (1) comparison with testis models, (2) an orchidometer, and (3) measurement of testicular volume by calipers through the scrotal skin. Data from these methods were compared with the actual volume measured at operation by slide calipers placed directly on the testis. The volume obtained by comparison with testis models or with an orchidometer tended to over-estimate the actual volume. The volume measured by slide calipers on scrotal skin was also found to be incorrect. On the other hand, the volume measured by ultrasonography proved to be closer to, and to correlate well with, the actual volume, and was considered to be the best method. PMID- 2201648 TI - Immunization with Treponema pallidum endoflagella alters the course of experimental rabbit syphilis. AB - Rabbits were immunized over a 32-week period with a total of 450 micrograms of purified Treponema pallidum endoflagella. As measured by enzyme-linked immunosorbent assay, sera from immunized rabbits had antiendoflagellar antibody titers that were fivefold greater than titers of sera from infected immune rabbits and patients with secondary disease. Sera from all immunized animals possessed complement-dependent treponemicidal activity as measured by in vitro immobilization. Immunized animals challenged with virulent T. pallidum were not protected from symptomatic infection but showed an altered course of lesion development. PMID- 2201650 TI - Improvement in the assessment of human epididymal function by the use of inhibitors in the assay of alpha-glucosidase in seminal plasma. AB - Seminal alpha-glucosidase has been used clinically as a marker of epididymal function. In this study enzyme inhibitors were used to increase the specificity of the human seminal alpha-glucosidase assay and improve its diagnostic value as an indicator of distal epididymal occlusion in cases of azoospermia. Sodium dodecylsulphate was added to the sample to eliminate the interfering acid isoenzyme secreted by the prostate gland, and castanospermine was used with semen pools to provide a semen blank for the assay by eliminating non-glucosidase regulated degradation of the substrate. With both inhibitors included in the assay, glucosidase activity in semen samples from 17 fathers was measured to provide reference values for the clinic (lower threshold 18 mU per ejaculate). With the improved assay glucosidase was non-detectable in 8 out of 11 cases of proven and 5 out of 8 cases of suspected ductal obstruction; other azoospermic patients with distal occlusion had values below 11 mU per ejaculate. PMID- 2201651 TI - Temocillin: lymph penetration and protein binding. AB - Temocillin, a novel betalactam antibiotic, was administered in doses of 1,2 and 4 g i.v. to 12 healthy subjects and the plasma concentrations of free and protein bound temocillin assayed and protein binding parameters were calculated. In a second study 2 g of temocillin was administered i.v. to 12 healthy subjects and samples of lymph were collected and assayed for total temocillin. Using the protein binding parameters so obtained the corresponding free temocillin in lymph was calculated. The clinical significance of the lymph penetration is discussed. PMID- 2201652 TI - Role of acetyl-L-carnitine in the treatment of cognitive deficit in chronic alcoholism. AB - Preliminary data are reported from a multicentred double-blind placebo-controlled study concerned with the effects of acetyl-L-carnitine (LAC) on some cognitive deficits of at least one month-abstinent alcoholics. Fifty-five patients, showing impaired performance in at least two out of six mnemonic, praxic and verbal tasks, were randomly assigned to either LAC 2 g/day or a placebo group. They were tested by means of a neuropsychological battery exploring the areas of memory, constructional praxia, deductive-logical functions and language. Testing time was on baseline (T0), after 45 (T45) and 90 (T90) days. On the Rey's 15 word memory test (long-term), the Wechsler memory scale (logical memory), and the Similarities WAIS subtest, the T90 difference between LAC and the placebo was significant in favour of the former treatment. On the copying drawing test (simple copy), the placebo group did not show any T0-T90 variation, while significant improvement in the LAC group was greater than in the placebo group. As LAC has proved to ameliorate the performance or to accelerate the recovery on tests representative of all cognitive areas explored, it is conceivable that the drug acts diffusely, either at the cholinergic transmission or at the neuronal metabolism level. It is concluded that acetyl-L-carnitine can be a useful and safe therapeutic agent in the subtle cognitive disturbances of chronic alcoholics. PMID- 2201653 TI - Physiological effects of acetyl-levo-carnitine in the central nervous system. AB - Acetyl-levo-carnitine (ALC) is a neuroactive agent. Some studies demonstrate that it modifies cortical electrophysiological responses in animals and man. Foremost, neuronal synchrony appears to be affected. It is thought that ALC is involved in cholinergic neurotransmission although some of its effects may be more complex. Electrophysiological processes involved in cognition may be influenced by ALC: in particular P300, an event-related potential, can be modified. Recent research data in man and monkeys concerning presumed ALC effects on P300 and cognition are summarized. PMID- 2201654 TI - Methodology of a controlled clinical study for cerebral aging evaluation. AB - A multicentre study was planned and executed to evaluate the effect of acetyl-L carnitine in the treatment of cerebral aging. Using 42 health centres, whose comparability of methodology was ensured through a training seminar and an instructional booklet on the psychometric battery of tests employed, some 400 elderly patients aged 60-80 years were enrolled using strict selection criteria. Treatment was run in four phases over 150 days. The first phase, serving as the baseline evaluation, defined through a battery of tests, consisted of 30-day placebo treatment. In the second phase of 45 days, daily treatment with 1500 mg acetyl-L-carnitine was given followed by a psychometric evaluation. For the next 45 days the same drug therapy was employed with a complete psychometric evaluation on the final day. In the last phase of 30 days the placebo was again administered and a final assessment made of the residual benefits of the 90-day treatment with acetyl-L-carnitine. Using this plan made it possible to evaluate the placebo effects, perform cross-study comparisons and demonstrate the effectiveness of the drug treatment. PMID- 2201655 TI - Nerve growth factor activity and aging in CNS. AB - This is a discussion of aging in CNS and the influence of the nerve growth factor (NGF) protein. The paper considers neuronal plasticity and neuronotrophic substances, neuronal cell death and the nerve growth factor protein, including its effects, receptors, and model systems for the study of CNS aging. PMID- 2201656 TI - Peroxidative stress and cerebral aging. AB - In order to test the hypothesis that cerebral nuclei showing age-related neuronal depletion would also show signs of vulnerability in their free radical scavenger systems and accumulation of the compounds resulting from peroxidation, the regional levels of a number of compounds were measured in mouse brains. With the exception of the tocopherols all the antioxidants had lower concentrations in the Substantia nigra which showed the most severe neuronal depletion with age. Acetyl L-carnitine is being investigated as a determinant of neuronal longevity. PMID- 2201657 TI - Ultrastructural aspects of aging rat hippocampus after long-term administration of acetyl-L-carnitine. AB - In aged rats a decrease in axosomatic synapses of granule cells as well as a decrease in the number of synaptic vesicles of giant synapses was found. These phenomena were supposed to be correlated on the basis of a feed-back circuit existing at the level of the dentate gyrus. In fact the axosomatic synapses of the granules are inhibitory gamma-aminobutyric acid-ergic terminals of interneurons. Interneurons receive excitatory afferences from granules via the giant synapses of the mossy fibre collaterals. This results in a feed-back regulation of granule cell activity. The long-term administration of acetyl-L carnitine to aged rats restores a synaptic pattern comparable to that of young rats. This effect on synaptic plasticity is transient. PMID- 2201658 TI - Neuroendocrine aspects of cerebral aging. AB - In their study of the neuroendocrine aspects of cerebral aging the authors review the effect of glucocorticoids, their participation in the mechanisms of neuronal loss and their beneficial and destructive effects. They discuss the treatment strategies for showing the destructive aspects of aging and the effect of acetyl L-carnitine in rats. They conclude that age-related degeneration of neural tissue is the complex result of multiple factors which synergize to cause neural destruction, including endogenous excitatory amino acids, calcium ions, endogenous proteolytic enzymes, free radicals and circulating glucocorticoids. It is considered that acetyl-L-carnitine may have protective effects in rats. PMID- 2201659 TI - Acetyl-L-carnitine in the treatment of mildly demented elderly patients. AB - It has been hypothesized that acetyl-L-carnitine has a cholinomimetic action. It is for this reason that it has been used in the therapy of Alzheimer's type senile dementia impairment. In the present controlled double-blind study the authors followed two randomized homogeneous groups of both sexes of 30 patients each, aged over 65 years and suffering from mild mental impairment. One group of patients underwent therapy with acetyl-L-carnitine, 2 g/day for three months, while the other group was treated with a placebo. The statistical evaluation of the results was carried-out using non-parametric methods (Friedman-Nemenyi two way ANOVA). It was possible to affirm that the acetyl-L-carnitine treated patients showed statistically significant improvement in the behavioural scales, in the memory tests, in the attention barrage test and in the Verbal Fluency test. These satisfactory results confirm the therapeutic importance of acetyl-L carnitine in the treatment of elderly patients with mental impairment, which could be related principally to acetylcholine defects. PMID- 2201660 TI - Pharmaco-electroencephalographic and clinical effects of the cholinergic substance--acetyl-L-carnitine--in patients with organic brain syndrome. AB - In two double-blind, placebo-controlled clinical studies of the nootropic compound acetyl-L-carnitine on the electroencephalogram (EEG) and impaired brain functions of elderly outpatients with mild to moderate cognitive decline of the organic brain syndrome, statistically significant effects could be detected after eight weeks (on the EEG), and after 12 weeks of treatment (on the physician's clinical global impression and the patient-rated level of activities of daily living). Side-effects of acetyl-L-carnitine were generally minor and overall rare. Longer treatment periods and further specifications with regard to the aetiopathology and degree of cognitive impairment are recommended for further clinical studies of this promising compound. PMID- 2201661 TI - Localization of iodopsin in the chick retina during in vivo and in vitro cone differentiation. AB - Using highly specific antibodies against a chick red-sensitive cone pigment, iodopsin, we investigated the localization of iodopsin in the developing and mature chick retina. The chick retina contains several different photoreceptor types, including a rod, a double cone with a principal and accessory cone, and four different types of single cones. Immunocytochemical observations revealed that outer segments (OS) of one of the single cones (type 1) and both cells of the double cone were strongly immunoreactive to anti-iodopsin antibodies. The Golgi regions and small vesicular structures in the inner segments (IS) of these cells also were intensely stained, indicating a continuous synthesis of iodopsin and its addition to the newly formed cone OS. In the differentiating cones of the developing but immature chick retina, iodopsin immunoreactivity was found at the plasma membranes of both the IS and the terminals (pedicles). This suggests that unidirectional transport of iodopsin to the outer segment may be established during cone differentiation. Immunostaining in the outer plexiform layer (OPL) produced two bands, suggesting that the pedicles of the double cones and type 1 single cones terminate at different positions in this layer. Application of the antibodies to a cell culture system of the chick retina revealed that cells immunoreactive to anti-iodopsin differ slightly in morphology from those reactive with anti-rhodopsin. Since antibodies to iodopsin and rhodopsin stained different types of photoreceptors in the intact chick retina, it will be possible to analyze cell lineage of rods and cones in vitro by use of these antibodies. PMID- 2201662 TI - Evaluation of an iris color classification system. The Eye Disorders Case-Control Study Group. AB - A system for classification of iris color based on standard photographs, developed for use in a multicenter study, is described. Categories of iris color are distinguished based on predominant color (blue, gray, green, light brown, or brown) and the amount of brown or yellow pigment present in the iris. Two trained readers independently graded 339 iris photographs; discrepancies in grades were adjudicated. Measures of interobserver reliability were 0.76 by kappa for exact agreement and 0.97 for weighted kappa. The distribution of iris color grades demonstrates that the system achieved an appropriate level of detail within the authors' study population, which included patients with various racial backgrounds from five urban clinical centers. This simple, reliable classification system for iris color is offered for use in clinical research. PMID- 2201663 TI - Leuko-araiosis: a reappraisal. I. CT studies. AB - Leuko-araiosis is a purely descriptive term indicating images of bilateral, patchy or diffuse areas of decreased density frequently observable in the deep white matter on brain CT scans of adults and elderly subjects. While in earlier studies these images were considered as the "in vivo" expression of leukoencephalopathy associated with Binswanger disease, subsequently they have been reported in a rather broad spectrum of clinical conditions, including healthy aging and dementia of different types. Evidence of arterial hypertension and lacunar stroke is found in only two-thirds of subjects with leuko-araiosis. The results of pathological studies are conflicting about the nature of leukoencephalopathy, and the type and severity of medullary artery involvements. Probably several mechanisms underlie leuko-araiosis. They might act separately or be combined in different cases. Classification by physiopathological mechanism may be a suitable aim of future research in this field. PMID- 2201664 TI - Tremor in Parkinson disease: acute response to oral levodopa. AB - A single blind placebo-controlled study has been performed in order to investigate objectively the acute tremorolytic effect of oral L-Dopa in ten parkinsonians chronically treated with L-Dopa. Finger tremor was assessed by means of a computerized accelerometer method, at rest and during maintenance of a fixed posture. Both resting and postural tremor were significantly influenced by L-Dopa. An "acute test" with oral L-Dopa, especially when different tremor components are investigated, may be useful for identifying objectively parkinsonians whose tremor does not respond to drug therapy or shows a deterioration of drug-responsiveness. PMID- 2201665 TI - Characteristics of antineuronal antibodies in systemic lupus erythematosus patients with and without central nervous system involvement: the role of mycobacterial cross-reacting antigens. AB - Sera of 16 patients with systemic lupus erythematosus (SLE) and active involvement of the CNS were examined for the presence of antibodies to human brain neurons, using indirect immunofluorescence of human brain tissue sections. Thirteen of the 16 patients (81%) had high antineuronal titers, which declined during convalescence, compared with 18 of 105 (17%) SLE patients who had no CNS disease. Competition assays showed that the binding of the antineuronal antibodies was blocked by mycobacterial glycolipids and bovine brain extracts. This finding suggests an additional link between mycobacterial infection and SLE. PMID- 2201666 TI - Ambulatory treatment of psoriasis with short-contact Dithrocream therapy: a multicenter study. PMID- 2201667 TI - Recent advances in interleukin-3 research: a review. PMID- 2201668 TI - The tissue distribution in rats of [195mPt]carboplatin following intravenous, intraperitoneal and oral administration. AB - [195mPt]carboplatin has been administered intravenously, intraperitoneally and orally to Wistar rats and the tissue distribution, metabolism, and pharmacokinetics of the drug investigated. The urinary and faecal excretion and toxicity following oral [195mPt]carboplatin administration has also been studied. Virtually identical results have been observed following i.v. and i.p. administration, indicating a rapid absorption of the unaltered compound from the abdominal cavity into the systemic circulation. Thus i.p. administered drug should produce a similar therapeutic response as i.v. administration, but may produce an additional local effect within the peritoneal cavity. Orally administered compound shows a pattern of distribution which is similar to that following parenteral injection for all tissues (except for the increased relative concentration in the stomach tissue), the concentration being lower by a factor of 4-5. However, the overall fraction of the dose retained within the body at 24 h is similar to that following i.v. administration. The toxicity is considerably lower for the orally administered drug compared with i.v. injection. These results clearly show that oral doses could be adjusted to produce a comparable therapeutic effect as i.v. or i.p. doses, and should also result in a higher efficacy against gastric carcinomas than achievable with parenteral administration. PMID- 2201669 TI - Lysosomal cytochemistry in marine environmental monitoring. PMID- 2201670 TI - Tola Rank. PMID- 2201671 TI - The dual meaning of repression and the adaptive design of the human psyche. PMID- 2201673 TI - Biosynthetic studies on oleandomycin by incorporation of the chemically synthesized aglycones. PMID- 2201672 TI - Synthesis and antibacterial activity of C-2 carboxyethenylthio-carbapenem derivatives. AB - A number of C-2 carboxyethenylthio-carbapenem derivatives possessing either the (5R,6R,8S)- or the (5R,6S,8R)-stereochemistries have been prepared from the olivanic acids MM 22382 (1) and MM 22383 (4), respectively. Their in vitro antibacterial activities and stabilities to human kidney homogenate are superior to those of the parent compounds, particularly in the latter series. PMID- 2201674 TI - Developments in family systems theory and research. AB - Contemporary family systems theory and therapy complement child and adolescent psychiatrists' interests in advocating for children. This paper reviews major developments in the family systems field which can be valuable contributions to child and adolescent psychiatry and mental health. Advances in therapy with difficult clinical populations are summarized. Theoretical frameworks and applications in the areas of human development and the family life cycle, family assessment, and family systems therapy are described. PMID- 2201675 TI - Epidemiology of childhood depressive disorders: a critical review. AB - The methodology of 14 recent epidemiological studies of childhood and adolescent depressive disorders was critically reviewed and findings summarized for prevalence, comorbidity, correlates, risk factors, and outcome. Shortcomings in sampling and considerable inconsistency in the measurement of depression in the studies made it difficult to draw firm conclusions about the prevalence and correlates of depression in young people. Nonetheless, it is likely that major depressive disorder is relatively uncommon in prepubertal children, increases in frequency in adolescents, and is significantly associated with such variables as family dysfunction and low self-esteem. Comorbidity of depression with other psychiatric disorders was also high in these nonpatient samples and it will be important in future work to assess the implications of this for the etiology, treatment, and prognosis of depressive disorders in children and adolescents. PMID- 2201676 TI - Chronic granulocytic leukaemia. PMID- 2201677 TI - Hydatid cyst of kidney presenting as hydatiduria. PMID- 2201678 TI - Regulation of cell cycle-dependent gene expression in yeast. PMID- 2201679 TI - The major native proteins of the leprosy bacillus. AB - This study addresses a major obstacle to vaccine development for leprosy, the isolation and characterization of the native protein antigens of the leprosy bacillus. Mycobacterium leprae harvested from armadillos was subjected to a simple fractionation protocol to arrive at the three major subcellular fractions, cell walls, cytoplasmic membrane, and soluble cytoplasm. The application of extensive detergent phase separations to membrane fractions allowed removal of lipoarabinomannan and the mannosyl phosphatidylinositols, and the recognition and purification of two major membrane proteins (MMP) of molecular mass 35 kDa (MMP I) and 22 kDa (MMP-II); recovery of these proteins was about 0.5 mg each per g of M. leprae. MMP-I is N-blocked and is perhaps a lipoprotein. End group analysis on MMP-II indicates a new protein. Three major cytoplasmic proteins (MCP) of molecular mass 14 kDa (MCP-I), 17 kDa (MCP-II), and 28 kDa (MCP-III) were also recognized. MCP-I, the most abundant protein in M. leprae, represents 1% of the bacterial mass. End group analysis of the first 30 residues and immunoblotting studies demonstrate sizeable structural homology to a protein from Mycobacterium tuberculosis but immunological distinctiveness. MCP-I, which also occurs in highly immunogenic peptidoglycan-bound form, is a primary candidate for future vaccine development. The cell walls of M. leprae are also characterized by one major extractable protein, also of molecular mass 17 kDa. Thus the major antigens of the leprosy bacillus, protein and carbohydrate alike, are now nearer to complete definition. PMID- 2201680 TI - Monocyte colony-stimulating factor enhances uptake and degradation of acetylated low density lipoproteins and cholesterol esterification in human monocyte-derived macrophages. AB - We have investigated effects of monocyte colony-stimulating factor (M-CSF) on the uptake of acetylated low density lipoproteins (acetyl-LDL) and the activity of cholesterol esterification in human monocyte-derived macrophage. The cells were cultured with M-CSF for 10 days and then incubated with acetyl-LDL for 24 h. M CSF (128 ng/ml) enhanced the uptake and degradation of 10 micrograms/ml of 125I acetyl LDL 7.5-fold (n = 6) and the effect of M-CSF was dose-dependent at the concentrations of 0.5-32 ng/ml. The binding experiments at 4 degrees C demonstrated that the number of acetyl-LDL receptor was increased by the addition of M-CSF. Supporting this, ligand blotting analysis revealed a significant increase in a receptor protein for acetyl-LDL (240 kDa). Binding of LDL was also enhanced by M-CSF but less significantly than that of acetyl-LDL. Cellular cholesterol esterification in the presence of 10 micrograms/ml acetyl-LDL was enhanced 24.1-fold (n = 13) by 128 ng/ml M-CSF. It was evident that M-CSF enhanced cholesterol esterification to a greater extent than the cellular uptake of acetyl-LDL (24.1- versus 7.5-fold). Cholesterol esterification was also enhanced by the addition of granulocyte-macrophage colony-stimulating factor and interleukin 1. We conclude that M-CSF enhances the uptake of both acetyl-LDL and LDL by increasing their receptor number, and further enhances the process of cholesterol esterification, resulting in a remarkable increase in cholesterol esterification in macrophages. These findings strongly suggest the significant involvement of cytokines such as M-CSF in cholesterol metabolism of macrophages. PMID- 2201681 TI - The hydrolysis of endothelins by neutral endopeptidase 24.11 (enkephalinase). AB - Endothelins 1-3 are a family of 21-amino acid peptides whose structure consists of two rings formed by intra-chain disulfide bonds and a linear "COOH-terminal tail." These peptides were originally described on the basis of their potent vasoconstrictor activity. The hydrolytic inactivation of endothelin action has recently been implicated to be attributed, at least in part, to the enzyme neutral endopeptidase 24.11 (Scicli, A. G., Vijayaraghavan, J., Hersh, L., and Carretero, O. (1989) Hypertension 14, 353). The kinetic properties and mode of hydrolysis of the endothelins by this enzyme are reported in this study. The Km for endothelins 1 and 3 hydrolysis is approximately 2 microM while endothelin2 exhibits a 5-fold higher Km. Endothelins 1 and 2 exhibit similar Vmax values while endothelin3 is hydrolyzed considerably more slowly. The initial cleavage site in endothelin1 is at the Ser5-Leu6 bond located within one of the cyclic structures. Thermolysin, a bacterial neutral endopeptidase with a similar substrate specificity to neutral endopeptidase 24.11 initially cleaves endothelin1 between His16-Leu17 which lies within the COOH-terminal linear "tail" portion of the molecule. The cleavage of endothelins 2 and 3 by neutral endopeptidase 24.11 differs from that observed with endothelin1 in that cleavage of these endothelins occurs at Asp18-Ile19 within the linear COOH-terminal tail structure. These results demonstrate that the endothelins are good substrates for neutral endopeptidase 24.11 and suggest that their mode of cleavage is dependent upon both amino acid sequence as well as peptide conformation. PMID- 2201683 TI - Serine hydroxymethyltransferase catalyzes the hydrolysis of 5,10 methenyltetrahydrofolate to 5-formyltetrahydrofolate. AB - The combined activities of rabbit liver cytosolic serine hydroxymethyltransferase and C1-tetrahydrofolate synthase convert tetrahydrofolate and formate to 5 formyltetrahydrofolate. In this reaction C1-tetrahydrofolate synthase converts tetrahydrofolate and formate to 5,10-methenyltetrahydrofolate, which is hydrolyzed to 5-formyltetrahydrofolate by a serine hydroxymethyltransferase glycine complex. Serine hydroxymethyltransferase, in the presence of glycine, catalyzes the conversion of chemically synthesized 5,10-methenyltetrahydrofolate to 5-formyltetrahydrofolate with biphasic kinetics. There is a rapid burst of product that has a half-life of formation of 0.4 s followed by a slower phase with a completion time of about 1 h. The substrate for the burst phase of the reaction was shown not to be 5,10-methenyltetrahydrofolate but rather a one carbon derivative of tetrahydrofolate which exists in the presence of 5,10 methenyltetrahydrofolate. This derivative is stable at pH 7 and is not an intermediate in the hydrolysis of 5,10-methenyltetrahydrofolate to 10 formyltetrahydrofolate by C1-tetrahydrofolate synthase. Cytosolic serine hydroxymethyltransferase catalyzes the hydrolysis of 5,10 methenyltetrahydrofolate pentaglutamate to 5-formyltetrahydrofolate pentaglutamate 15-fold faster than the hydrolysis of the monoglutamate derivative. The pentaglutamate derivative of 5-formyltetrahydrofolate binds tightly to serine hydroxymethyltransferase and dissociates slowly with a half life of 16 s. Both rabbit liver mitochondrial and Escherichia coli serine hydroxymethyltransferase catalyze the conversion of 5,10-methenyltetrahydrofolate to 5-formyltetrahydrofolate at rates similar to those observed for the cytosolic enzyme. Evidence that this reaction accounts for the in vivo presence of 5 formyltetrahydrofolate is suggested by the observation that mutant strains of E. coli, which lack serine hydroxymethyltransferase activity, do not contain 5 formyltetrahydrofolate, but both these cells, containing an overproducing plasmid of serine hydroxymethyltransferase, and wild-type cells do have measurable amounts of this form of the coenzyme. PMID- 2201682 TI - Crystallographic analysis of a complex between human immunodeficiency virus type 1 protease and acetyl-pepstatin at 2.0-A resolution. AB - The mode of binding of acetyl-pepstatin to the protease from the human immunodeficiency virus type 1 (HIV-1) has been determined by x-ray diffraction analysis. Crystals of an acetyl-pepstatin-HIV-1 protease complex were obtained in space group P2(1)2(1)2 (unit cell dimensions a = 58.39 A, b = 86.70 A, c = 46.27 A) by precipitation with sodium chloride. The structure was phased by molecular replacement methods, and a model for the structure was refined using diffraction data to 2.0 A resolution (R = 0.176 for 12901 reflections with I greater than sigma (I); deviation of bond distances from ideal values = 0.018 A; 172 solvent molecules included). The structure of the protein in the complex has been compared with the structure of the enzyme without the ligand. A core of 44 amino acids in each monomer, including residues in the active site and residues at the dimer interface, remains unchanged on binding of the inhibitor (root mean square deviation of alpha carbon positions = 0.39 A). The remaining 55 residues in each monomer undergo substantial rearrangement, with the most dramatic changes occurring at residues 44-57 (these residues comprise the so-called flaps of the enzyme). The flaps interact with one another and with the inhibitor so as to largely preserve the 2-fold symmetry of the protein. The inhibitor is bound in two approximately symmetric orientations. In both orientations the peptidyl backbone of the inhibitor is extended; a network of hydrogen bonds is formed between the inhibitor and the main body of the protein as well as between the inhibitor and the flaps. Hydrophobic side chains of residues in the body of the protein form partial binding sites for the side chains of the inhibitor; hydrophobic side chains of residues in the flaps complete these binding sites. PMID- 2201684 TI - Metal binding to DNA polymerase I, its large fragment, and two 3',5'-exonuclease mutants of the large fragment. AB - DNA polymerase I (Pol I) is an enzyme of DNA replication and repair containing three active sites, each requiring divalent metal ions such as Mg2+ or Mn2+ for activity. As determined by EPR and by 1/T1 measurements of water protons, whole Pol I binds Mn2+ at one tight site (KD = 2.5 microM) and approximately 20 weak sites (KD = 600 microM). All bound metal ions retain one or more water ligands as reflected in enhanced paramagnetic effects of Mn2+ on 1/T1 of water protons. The cloned large fragment of Pol I, which lacks the 5',3'-exonuclease domain, retains the tight metal binding site with little or no change in its affinity for Mn2+, but has lost approximately 12 weak sites (n = 8, KD = 1000 microM). The presence of stoichiometric TMP creates a second tight Mn2+ binding site or tightens a weak site 100-fold. dGTP together with TMP creates a third tight Mn2+ binding site or tightens a weak site 166-fold. The D424A (the Asp424 to Ala) 3',5'-exonuclease deficient mutant of the large fragment retains a weakened tight site (KD = 68 microM) and has lost one weak site (n = 7, KD = 3500 microM) in comparison with the wild-type large fragment, and no effect of TMP on metal binding is detected. The D355A, E357A (the Asp355 to Ala, Glu357 to Ala double mutant of the large fragment of Pol I) 3',5'-exonuclease-deficient double mutant has lost the tight metal binding site and four weak metal binding sites. The binding of dGTP to the polymerase active site of the D355A,E357A double mutant creates one tight Mn2+ binding site with a dissociation constant (KD = 3.6 microM), comparable with that found on the wild-type enzyme, which retains one fast exchanging water ligand. Mg2+ competes at this site with a KD of 100 microM. It is concluded that the single tightly bound Mn2+ on Pol I and a weakly bound Mn2+ which is tightened 100 fold by TMP are at the 3',5'-exonuclease active site and are essential for 3',5' exonuclease activity, but not for polymerase activity. Additional weak Mn2+ binding sites are detected on the 3',5'-exonuclease domain, which may be activating, and on the polymerase domain, which may be inhibitory. The essential divalent metal activator of the polymerase reaction requires the presence of the dNTP substrate for tight metal binding indicating that the bound substrate coordinates the metal.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2201685 TI - The histamine degradative uptake pathway in human vascular endothelial cells and skin fibroblasts is dependent on extracellular Na+ and Cl-. AB - We have previously reported that human vascular endothelial cells and skin fibroblasts carry out degradation of [3H]histamine by a mechanism involving two successive enzymatic steps: imidazole ring tele-methylation by the cells' endogenous methyltransferase and subsequent amine oxidation by an exogenous diamine oxidase. Both histamine and the exogenous second enzyme in the pathway associate with the cells via separate binding sites or receptors. The enzymatic degradation process results in cellular accumulation of the proximal and distal metabolites tele-methylhistamine and 1-methyl-4-imidazoleacetic acid (MIAA) (Haddock, R. C., Mack, P., Fogerty, F. J., and Baenziger, N. L. (1987) J. Biol. Chem. 262, 10220-10228). We have now demonstrated that this two-stage histamine degradative pathway is dependent on Na+ and Cl- in the extracellular environment. Accumulation of [3H] histamine-derived products is partially inhibited under conditions of Na+ deprivation and more substantially when Cl- is also withdrawn. The individual tele-methylation and amine oxidation enzymatic reactions themselves are unaffected or actually facilitated under these conditions. This indicates that it is the cellular mechanism for uptake coupled to the degradative pathway which reflects the cation and anion dependency. Restoration of degradative uptake displays a biphasic Na+ concentration curve, suggesting that the uptake process may be driven by multiple components. These findings indicate a role for both inward Na+ and Cl- ion movement in this cellular degradative uptake mechanism. PMID- 2201686 TI - Substrate specificity of the protease that processes human interleukin-1 beta. AB - The substrate specificity of the protease which generates mature human interleukin-1 beta (IL-1 beta) from pro-interleukin-1 beta was investigated using synthetic peptide substrates and recombinant pro-IL-1 beta. The requirement of an L-aspartate in the P-1 position was confirmed together with the need for a small hydrophobic residue in the P-1' position (Gly or Ala). It was shown that the enzyme can tolerate conservative substitutions in the P-2 and P-2' positions. We found little difference in the enzyme's ability to cleave denatured and native pro-IL-1 beta, indicating that tertiary structure recognition is not involved in binding. The enzyme did, however, require a peptide of more than six amino acids for cleavage to occur. These results conclusively demonstrate the unusual specificity of this protease. PMID- 2201687 TI - Molecular analysis of the Escherichia coli ferric enterobactin receptor FepA. AB - In Escherichia coli, the outer membrane protein FepA is a receptor for the siderophore complex ferric enterobactin and for colicins B and D. To identify protein domains important for FepA activity, the effects of deletion and linker insertion mutations on receptor structure and function were examined. In-frame internal deletion mutations removing sequences encoding up to 304 amino acid residues resulted in functionally defective FepA polypeptides, although most were translocated efficiently to the outer membrane. One exception, a derivative lacking 87 internal amino acid residues near the N terminus, showed an inability to transport ferric enterobactin but retained limited colicin receptor function. Analysis of cells carrying 3'-terminal fepA deletion mutations suggested that residues within the C terminus of FepA may be involved in secretion and proper translocation of the protein to the outer membrane. Introduction of the peptide Leu-Glu after FepA residues 55, 142, or 324 severely impaired receptor function for all three ligands, while the same insertion after residues 339 or 359 had virtually no detrimental effect on FepA function. Foreign peptides inserted after residues 204 or 635 restricted colicin B and D function only, leaving ferric enterobactin transport ability at near wild-type levels. The results presented in this study have identified key regions of FepA potentially involved in receptor function and demonstrate the presence of both shared and unique ligand-responsive domains. PMID- 2201689 TI - Purification of a phospholipase A2 from human monocytic leukemic U937 cells. Calcium-dependent activation and membrane association. AB - The existence of an intracellular phospholipase A2 (PLA2) involved in the production of 1-O-alkyl-sn-glycero-3-phosphocholine and free arachidonic acid has been repeatedly postulated. Using 1-O-hexadecyl-2-[3H]arachidonoyl-sn-glycero-3 phosphocholine as a substrate and a series of conventional and high-pressure liquid chromatographic techniques, we have purified a PLA2 from the soluble fraction of differentiated human monocytic U937 cells. The enzyme has been purified nearly 2000-fold to homogeneity. The purified enzyme has a molecular mass of 56 kDa, under reducing conditions, by sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis. The enzyme activity has a pH optimum of 8.0 and is calcium concentration-dependent. The EC50 for the activation of the enzyme activity by calcium is 300 nM. When the cells were homogenized in the presence of the calcium chelator EGTA (0.2 mM), the enzyme was found to be soluble (more than 90% of the activity in the 100,000 x g supernatant). However, when Ca2+ concentration was controlled from 10 nM to 100 microM in Ca2(+)-EGTA buffers, increasing amounts of the activity were found in the particulate fraction (100,000 x g pellet). This suggests that membrane translocation and activation of the soluble PLA2 may be regulated by physiological intracellular levels of Ca2+. The purified enzyme hydrolyzed different phosphatidylcholine substrates presented in either vesicular or Triton X-100 mix micellar forms. In both situations, the enzyme showed a high degree of specificity for arachidonic acid on the sn-2 position of the substrate. Substitution of palmitic or oleic on the sn-2 position substantially reduced the hydrolytic activity of the enzyme. When vesicles of arachidonic acid-containing phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol were presented to the purified enzyme, all of them were hydrolyzed with comparable efficiency. However, only phosphatidylcholine and phosphatidylinositol were hydrolyzed when presented in Triton X-100 mixed micelles. PMID- 2201688 TI - Identification of residues critical for the polymerase activity of the Klenow fragment of DNA polymerase I from Escherichia coli. AB - The Klenow fragment structure, together with many biochemical experiments, has suggested a region of the protein that may contain the polymerase active site. We have changed 7 amino acid residues within this region by site-directed mutagenesis, yielding 12 mutant proteins which have been purified and analyzed in vitro. The results of steady-state kinetic determinations of Km(dNTP) and kcat for the polymerase reaction, together with measurements of DNA binding affinity, suggest strongly that this study has succeeded in targeting important active site residues. Moreover, the in vitro data allow dissection of the proposed active site region into two clusters of residues that are spatially, as well as functionally, fairly distinct. Mutations in Tyr766, Arg841, and Asn845 cause an increase in Km(dNTP), suggesting that contacts with the incoming dNTP are made in this region. Mutations in the second cluster of residues, Gln849, Arg668, and Asp882, cause a large decrease in kcat, suggesting a role for these residues in catalysis of the polymerase reaction. The DNA-binding properties of mutations at positions 849 and 668 may indicate that the catalytic role of these side chains is associated with their interaction with the DNA substrate. Screening of the mutations in vivo for the classical polA-defective phenotype (sensitivity to DNA damage) demonstrated that a genetic screen of this type may be a reasonable predictor or kcat or of DNA binding affinity in future mutational studies. PMID- 2201690 TI - Contacts between the factor TUF and RPG sequences. AB - The yeast TUF factor binds specifically to RPG-like sequences involved in multiple functions at enhancers, silencers, and telomeres. We have characterized the interaction of TUF with its optimal binding sequence, rpg-1 (1-ACACCCATACATTT 14), using a gel DNA-binding assay in combination with methylation protection and mutagenesis experiments. As many as 10 base pairs appear to be engaged in factor binding. Analysis of a collection of 30 different RPG mutants demonstrated the importance of 8 base pairs at position 2, 3, 4, 5, 6, 7, 10, and 12 and the critical role of the central GC pair at position 5. Methylation protection data on four different natural sites confirmed a close contact at positions 4, 5, 6, and 10 and suggested additional contacts at base pairs 8, 12, and 13. The derived consensus sequence was RCAAYCCRYNCAYY. A quantitative band shift analysis was used to determine the equilibrium dissociation constant for the complex of TUF and its optimal binding site rpg-1. The specific dissociation constant (K8) was found to be 1.3 x 10(-11) M. The comparison of the K8 value with the dissociation constant obtained for nonspecific DNA sites (Kn8 = 8.7 x 10(-6) M) shows the high binding selectivity of TUF for its specific RPG target. PMID- 2201691 TI - Specificity and inhibition of proteases from human immunodeficiency viruses 1 and 2. AB - Highly purified, recombinant preparations of the virally encoded proteases from human immunodeficiency viruses (HIV) 1 and 2 have been compared relative to 1) their specificities toward non-viral protein and synthetic peptide substrates, and 2) their inhibition by several P1-P1' pseudodipeptidyl-modified substrate analogs. Hydrolysis of the Leu-Leu and Leu-Ala bonds in the Pseudomonas exotoxin derivative, Lys-PE40, is qualitatively the same for HIV-2 protease as published earlier for the HIV-1 enzyme (Tomasselli, A. G., Hui, J. O., Sawyer, T. K., Staples, D. J., FitzGerald, D. J., Chaudhary, V. K., Pastan, I., and Heinrikson, R. L. (1990) J. Biol. Chem. 265, 408-413). However, the rates of cleavage at these two sites are reversed for the HIV-2 protease which prefers the Leu-Ala bond. The kinetics of hydrolysis of this protein substrate by both enzymes are mirrored by those obtained from cleavage of model peptides. Hydrolysis by the two proteases of other synthetic peptides modeled after processing sites in HIV-1 and HIV-2 gag polyproteins and selected analogs thereof demonstrated differences, as well as similarities, in selectivity. For example, while the two proteases were nearly identical in their rates of cleavage of the Tyr-Pro bond in the HIV-1 gag fragment, Val-Ser-Gln-Asn-Tyr-Pro-Ile-Val, the HIV-1 protease showed a 64-fold enhancement over the HIV-2 enzyme in hydrolysis of a Tyr-Val bond in the same template. Accordingly, the HIV-2 protease appears to have a different specificity than the HIV-1 enzyme; it is better able to hydrolyze substrates with small amino acids in P1 and P1', but is variable in its rate of hydrolysis of peptides with bulky substituents in these positions. In addition to these comparisons of the two proteases with respect to substrate specificity, we present inhibitor structure-activity data for the HIV-2 protease. Relative to P1-P1' statine or Phe psi [CH2N]Pro-modified pseudopeptidyl inhibitors, compounds having Xaa psi[CH(OH)CH2]Yaa inserts were found to show significantly higher affinities to both enzymes, generally binding from 10 to 100 times stronger to HIV-1 protease than to the HIV-2 enzyme. Molecular modeling comparisons based upon the sequence homology of the two enzymes and x-ray crystal structures of HIV-1 protease suggest that most of the nonconservative amino acid replacements occur in regions well outside the catalytic cleft, while only subtle structural differences exist within the active site.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2201692 TI - Chromatographic and non-chromatographic assay of L-carnitine family components. AB - L-Carnitine and its acyl esters constitute an endogenous pool of the L-carnitine family, involved in the uptake of free fatty acids in the mitochondria by transfer across their membrane of the acyl moieties to fuel the beta-oxidation and the release of the acetyl group from the mitochondria to the cytosol. Therefore acyl-L-carnitine and acyl-L-carnitine transferase are involved in a homeostatic equilibrium with the cells. As most of these substances need to be monitored in foods, chemical and pharmaceutical processes and biological fluids, an overview of the main methods for assaying them is provided here, with specific reference to the intrinsic performance of each analytical procedure and with suggestions on the correct storage and manipulation of analytical samples. PMID- 2201693 TI - Direct serum injection high-performance liquid chromatographic method for the simultaneous determination of phenobarbital, carbamazepine and phenytoin. AB - A method is described for the simultaneous measurement of serum levels of three antiepileptic drugs, phenobarbital, phenytoin and carbamazepine, by direct injection high-performance liquid chromatography on a 25-cm Pinkerton internal surface reversed-phase (ISRP) column. Several commonly available compounds were tested and found not to co-chromatograph with the three drugs of interest or the internal standard, 5-(p-methylphenyl)-5-phenylhydantoin. Results obtained on patients' samples with this method compared well with those from enzyme multiplied immunoassay technique (EMIT). PMID- 2201694 TI - Determination of carboplatin in canine plasma by liquid chromatography with ultraviolet-visible detection and confirmation by atomic absorption spectroscopy. PMID- 2201695 TI - An indirect bonding technique. PMID- 2201696 TI - Recycling ceramic brackets. PMID- 2201697 TI - Debonding ceramic brackets. PMID- 2201698 TI - Flaws in bracket manufacturing. PMID- 2201699 TI - Long-term results following surgical treatment of internal derangement of the temporomandibular joint. AB - The long-term results achieved in 31 joints by means of discoplasty or (temporary) implantation of silastic for treatment of internal derangements are presented. These data support the philosophy of preserving the disc whenever possible. If, however, discectomy is inevitable this fibrous plate should be replaced. Interposition of a sheet of silastic for a period of 3-6 months has proven very useful as it has in surgery for ankylosis. Silastic induces formation of a scar located between fossa and condyle which is necessary for the preservation of both rotational and translatory movements. Our postoperative results have been stable for many years and the disadvantages noted by other authors have not been found in these patients. PMID- 2201700 TI - Odontogenic ghost cell tumours. The neoplastic form of calcifying odontogenic cyst. AB - The tumourous form of the calcifying odontogenic cyst is a rare entity and only a small number cases have been described in the medical literature published in English. Our report concerns a 66-year-old patient with a tumourous mass in the maxilla, with clear COC histological features, in addition to an infiltrative growth pattern of the epithelial islands and ghost cells invading the subjacent stroma, oral mucosa and peripheral maxillary bone. Cytoplasmic and nuclear pleomorphism and atypical mitoses were rarely found. An aggressive surgical approach produced a satisfactory result. We have reviewed the literature available in English and compared it with our case. PMID- 2201701 TI - A severe fibrotic reaction after cosmetic liquid silicone injection. A case report. AB - A case of a severe, locally aggressive fibroblastic reaction to cosmetic silicone injection involving the orbital cone and anterior cranial base is presented. Included is a brief history and description of silicone injection and its complications. Though many facts remain to be discovered, speculation into the possible pathogenesis, with a review of the literature, shows that while silicone continues to be a useful tool for the plastic surgeon, an awareness of the risks, as well as a search for clues to avoid complications, must continue before further liberal use of this material is encouraged. PMID- 2201702 TI - Genetic approaches in the study of periodontal diseases. AB - Periodontal diseases are essentially infectious in origin, their outcome depending on interaction between the pathogenic challenge and host response. Host genotype has been implicated in certain of the more unusual forms, but together these account for only a small proportion of periodontal patients. Nevertheless, the genes for these rarer conditions, some of which have already been located and/or cloned, are of considerable importance, since they may ultimately provide clues leading to a better understanding of the whole spectrum of periodontal disease. For the majority of periodontal patients, although inherited susceptibility is suspected, evidence of a significant genetic component is scanty. The priority here is therefore to establish the existence of contributing genes. This may be possible by using approaches designed to minimise the confounding effect of environmental variation that has probably been a source of confusion in the past. PMID- 2201703 TI - Bacteroides gingivalis stimulates bone resorption via interleukin-1 production by mononuclear cells. The relative role for B. gingivalis endotoxin. AB - Supernatants of human peripheral blood mononuclear cells cultured in the presence of B. gingivalis, showed a strong osteoclast stimulating activity as measured by 45Ca release from fetal mouse long bones in vitro. These supernatants also contained a high concentration of bioactive and immunoreactive interleukin-1 (IL 1), but tumor necrosis factor (TNFa), another osteoclast-activating cytokine, was not detected. Osteoclast activation by the supernatants was inhibited by an antibody against IL-1, whereas ultrapure human IL-1 mimicked the effect of the supernatant. The ability of B. gingivalis to induce IL-1 and OAF production was heat sensitive, as 20 min heating of the bacteria at 120 degrees C caused a 50% loss of activity. In addition, purified B. gingivalis lipopolysaccharide (LPS) had little IL-1 inducing capacity, compared with LPS of Escherichia coli. These data suggest that human peripheral blood cells confronted with B. gingivalis produce large amounts of IL-1 which has strong osteoclast stimulating activity. However, in contrast with E. coli LPS, B. gingivalis LPS does not seem to be the major inducing agent. Thus other bacterial components must be responsible for the observed IL-1 and OAF induction. PMID- 2201704 TI - Clinical, microbiological and immunological studies on recurrent periodontal disease. AB - The present study was performed to evaluate the clinical, microbiological and immunological aspects in the early stages of recurrent periodontal disease. After clinical monitoring of pockets with recent evidence of disease recurrence, microbiological samples for cultural analysis, serum and gingival crevicular fluid (GCF) samples were taken for IgG antibody analysis from 14 sites, 7 in 6 recurrent periodontitis patients and 7 in 7 periodontally healthy control subjects. IgG responses of serum antibody to 8 gram-negative bacterial strains were compared with those of GCF sampled from the recurrent site. The results clearly demonstrated the predominance of Bacteroides gingivalis in most subgingival plaque samples during the early stages of disease recurrence; the mean proportions of B. gingivalis were significantly different from those of the healthy sites (p less than 0.05). 4 out of 6 serum samples showed the elevated antibody responses to B. gingivalis 381; and this was closely correlated to homologous infection by this micro-organism in recurrent sites. Elevated serum antibody responses were also noted to Eikenella corrodens 1073 and Actinobacillus actinomycetemcomitans Y4. However, no relationship with homologous infection was found for A. actinomycetemcomitans. 3 out of 6 GCF samples had greater antibody titers than the serum, suggesting local antibody synthesis by the gingival cells in the recurrent pockets. The present study showed that B. gingivalis might play an important role in the pathogenesis of disease recurrence in its early stages. PMID- 2201705 TI - Split-mouth and cross-over designs in dental research. AB - The presence of paired or multiple organs (arches, quadrants, teeth) and the chronic nature of many dental diseases suggest the use of split-mouth (trials in which each subject receives greater than or equal to 2 treatments, each to a separate section of the mouth) and cross-over research designs (trials in which each subject receives greater than or equal to 2 treatments in sequence). While these designs offer potential savings in resources, their usefulness can be negated if several strict scientific and statistical assumptions are not met. The primary prerequisites for the use of split-mouth and cross-over designs are that: (1) the disease to be investigated is relatively stable and uniformly distributed; (2) the effects of the treatments to be evaluated are short-lived or reversible for cross-over studies, or are localized for split-mouth designs. Other important factors that influence the appropriate use of these designs include: the method of treatment sequencing and assignment, and the cross-over rules used; blinding of patient assignment, patients and observers; assessment of order effects including period, carry-over or spill-over effects; the choice of statistical analysis, the sample size utilized, and the special importance of patients lost to study or of faulty data points. The objective of this study was to review 3 journals for studies using split-mouth or cross-over designs to determine how the assumptions underlying these research designs are considered and applied in dental research. The majority of studies used adequate methods for treatment allocation and sequencing; however, many studies failed to take advantage of the research designs in the statistical analysis of data. In addition, very few studies considered the possibility of order effects or reduced bias through blinding procedures. PMID- 2201706 TI - Intracrevicular application of tetracycline in white petrolatum for the treatment of periodontal disease. AB - In vitro tests in our laboratory have shown that 40% tetracycline HCl in a white petrolatum carrier (TTC-WP) has potential as a sustained release, autodissipating system. The present study tested subgingival placement of TTC-WP via syringe in vivo. Quadrants (2 diseased sites in each) in 9 patients with moderate/severe periodontitis were randomly assigned to receive the following treatments: (1) TTC WP; (2) WP only; (3) scaling and root planing; (4) untreated control. TTC release into gingival crevicular fluid (GCF) over time (baseline, 1, 8, 24, 72 and 168 h) was measured using an agar diffusion bioassay. Clinical parameters and subgingival bacterial morphotypes (darkfield analysis) were also evaluated over time (baseline, 2, 4, 8, 12 weeks). Results indicated that TTC-WP was easily placed into periodontal pockets and biologically effective TTC was released into GCF for at least 3 days (mean concentration = 115.8 +/- 43.1 micrograms/ml at 3 days). TTC-WP reduced probing pocket depths and bleeding on probing relative to baseline measurements for 8-12 weeks post-treatment, and reduced %s of motile rods and spirochetes, with an accompanying increase in cocci, for 2-8 weeks. Similar effects were noted in the scaled and root-planed sites, but for a longer duration. TTC-WP and WP were clinically dissipated after 2 weeks and no adverse tissue reactions were observed. From these findings, subgingival TTC-WP cannot replace scaling and root planing therapy, but has characteristics useful in subgingival plaque control. PMID- 2201707 TI - [Dentures on osseointegrated implants: the complete fixed-removable lower denture (2)]. AB - This article is the second of a series of four. This article describes in detail the fabrication of a complete fixed-removable prosthesis connected to a dolder bar. PMID- 2201708 TI - [Tuberous sclerosis. Presentation of cases and review of the literature]. PMID- 2201709 TI - [Dentures on osseointegrated implants: the complete lower fixed denture (1)]. AB - This article is the first of a series of four. Each one summarizes the clinical and technical prosthetic stages of different types of restorations. This article describes in detail the fabrication of a complete fixed prosthesis using screw type osseointegrated implants. PMID- 2201710 TI - Determinants of prognosis in symptomatic ventricular tachycardia or ventricular fibrillation late after myocardial infarction. The Dutch Ventricular Tachycardia Study Group of the Interuniversity Cardiology Institute of The Netherlands. AB - In a multicenter study, 390 patients with sustained symptomatic ventricular tachycardia or ventricular fibrillation late after acute myocardial infarction were prospectively followed up to assess determinants of mortality and recurrence of arrhythmic events. Patients were given standard antiarrhythmic treatment, which consisted primarily of drug therapy. During a mean follow-up period of 1.9 years, 133 patients (34%) died; arrhythmic events and heart failure were the most common cause of death (41 patients [11%] died suddenly, 31 [8%] died because of recurrent ventricular tachycardia or ventricular fibrillation and 23 [6%] died of heart failure). One hundred ninety-two patients (49%) had at least one recurrent arrhythmic event; 85% of first recurrent arrhythmic events were nonfatal. Multivariate analysis of data from patients who developed the arrhythmia less than 6 weeks after infarction identified five variables as independent determinants of total mortality: 1) age greater than 70 years (risk ratio 4.5); 2) Killip class III or IV in the subacute phase of infarction (risk ratio 3.5); 3) cardiac arrest during the index arrhythmia (risk ratio 1.7); 4) anterior infarction (risk ratio 2.2); and 5) multiple previous infarctions (risk ratio 1.6). Multivariate analysis of data from patients developing the arrhythmia greater than 6 weeks after infarction identified four variables as independently predictive of total mortality: 1) Q wave infarction (risk ratio 2.1); 2) cardiac arrest during the index arrhythmia (risk ratio 1.7); 3) Killip class III or IV in the subacute phase of infarction (risk ratio 1.7); and 4) multiple previous infarctions (risk ratio 1.4). The results of the two multivariate analyses were used in a model for prediction of mortality at 1 year. The average predicted mortality rate varied considerably according to the model: for 243 patients (62%) with the lowest risk, it was 13%, corresponding to an observed mortality rate of 12%; for 92 patients (24%) with intermediate risk, it was 27%, corresponding to an observed rate of 28%; for 55 patients (14%) with the highest risk, it was 64%, corresponding to an observed rate of 54%. This study shows that patients with symptomatic ventricular tachycardia or ventricular fibrillation late after myocardial infarction who are given standard antiarrhythmic treatment have a high mortality rate. The predictive model presented identifies patients at low, intermediate and high risk of death and can be of help in designing the appropriate diagnostic and therapeutic strategy for the individual patient. PMID- 2201711 TI - Stroke complicating thrombolytic therapy of acute myocardial infarction. PMID- 2201712 TI - Intravascular ultrasonography versus digital subtraction angiography: a human in vivo comparison of vessel size and morphology. AB - The accuracy of catheter-based intravascular ultrasonography to define luminal size in humans in vivo and its sensitivity to describe lesion morphology have not been previously reported. Vessel diameter, cross-sectional area and lesion characteristics assessed by digital subtraction angiography and intravascular ultrasonography (20 MHz) were compared in 86 human arterial segments. The same arterial segments were imaged and analyzed by digital subtraction angiography and intravascular ultrasonography at 49 femoral, 3 renal, 5 iliac, 7 pulmonary and 22 aortic sites. Digital subtraction angiographic diameter and area were determined geometrically by an automated algorithm. Intravascular ultrasonographic diameter and area were determined by planimetry. Linear correlation for diameter by the two techniques was 0.97, standard error of the estimate (SEE) = 1.83 mm, and for cross-sectional area it was 0.95, SEE = 0.65 cm2. Intravascular ultrasonography identified 24 sites in which plaque was present; 11 (46%) of these segments appeared normal by digital subtraction angiography. Conversely, digital subtraction angiography demonstrated irregularities in 18 segments of which 5 (28%) appeared normal by intravascular ultrasonography. These data indicate an excellent correlation between intravascular ultrasonography and digital subtraction angiography for in vivo assessment of human arterial dimensions in normal and minimally diseased segments. However, intravascular ultrasonography is more likely to identify atherosclerotic plaque that may be angiographically "silent." PMID- 2201713 TI - Management of survivors of cardiac arrest: is electrophysiologic testing obsolete in the era of implantable defibrillators? PMID- 2201714 TI - Relation of cognitive status and abnormal behaviors in Alzheimer's disease. AB - Some studies suggest that abnormal behaviors are associated with increasing cognitive loss in Alzheimer's disease (AD). Other studies do not show this association. We examined the relation of cognitive loss, represented by Folstein Mini-Mental State Examination (MMSE) score, with abnormal behaviors in 680 patients with probable AD. Six behaviors were examined: agitation/anger, personality change, wandering, hallucinations/delusions, insomnia, and depression. All but depression were associated with declining MMSE score. The number of abnormal behaviors present in each patient was also related to declining MMSE score. Several other associations were also found: hallucinations/delusions were associated with age and race; agitation/anger was related to male gender; and wandering was associated with increased age. Although these data support the general notion that five of the six abnormal behaviors studied are more likely to occur with increasing cognitive loss, the correlations are small and it is suggested that other as yet unproven factors may play an as large or greater role than MMSE score in predicting such behaviors. PMID- 2201715 TI - Neuropeptides and Alzheimer's disease. AB - Because of their putative roles as neurotransmitters, neuromodulators, and neuroregulators in the central nervous system, neuropeptides have been the focus of considerable research over the past two decades. There is evidence that alterations in the synaptic availability of particular neuropeptides occur in certain neuropsychiatric disorders, such as schizophrenia and affective disorders. Alzheimer's disease is the most common neurodegenerative disorder, affecting a sizable proportion of our aging population. Alzheimer's disease is characterized by the presence of neurofibrillary tangles and senile plaques in the central nervous system. Postmortem studies have provided evidence that several neuropeptide-containing neurons are pathologically altered in this disorder. The purpose of this article is to describe recent advances in neuropeptide biology with a focus on the role of neuropeptides in the pathogenesis of Alzheimer's disease. PMID- 2201717 TI - Nursing home research. PMID- 2201716 TI - Inpatient geriatric consultation. Challenges and benefits. PMID- 2201718 TI - Drug abuse? Use and misuse of psychotropic drugs in Alzheimer's care. AB - Although psychotropic drugs are widely used to control symptoms related to dementia, concerns are raised by the potential for adverse effects and misuse. Antidepressants may be useful when depression and dementia coexist in the early stages of Alzheimer's disease. In later stages, anxiety and agitation are often treated with antianxiety or antipsychotic agents. Concerns escalate about the use of antipsychotic agents as chemical restraints. Nursing home reform provisions of OBRA '87 mandate dose reductions of antipsychotics in an effort to discontinue their use. The role of the nurse is to establish and monitor therapeutic goals, to assess the incidence and severity of predictable side effects, and to provide a safe, supportive environment that reduces the need for pharmacological intervention. PMID- 2201719 TI - Isolation, purification and characterization of surface antigens of the bovine filarial parasite Setaria digitata for the immunodiagnosis of bancroftian filariasis. AB - The surface antigens of the bovine filarial parasite Setaria digitata were isolated by EDTA extraction and purified by affinity chromatography using sepharose bound human filarial (Wuchereria bancrofti) antibodies obtained from chronic human filarial sera. The purified and crude antigens were used in enzyme linked immunosorbent assay (ELISA) for the detection of serum antibodies in bancroftian filariasis. The purified antigen showed sensitive and specific reactions in ELISA for the detection of antibodies in filarial sera and showed least cross reactivity with other parasitic infections. The crude and purified antigens showed about 18 and 6 peptide bands respectively in SDS-PAGE and about 11 and 6 antigenic bands respectively in enzyme-linked immunoelectrotransfer blot (EITB). The purified antigen was observed to be glycoprotein in nature. It was possible to identify the stage-specific infection in human filariasis by using the crude and purified antigens in EITB. PMID- 2201720 TI - Immunological analysis of Opisthorchis and Clonorchis antigens. AB - Immunoreactive components of Opisthorchis viverrini and Clonorchis sinensis were analysed by enzyme-linked immunosorbent assay (ELISA), radioimmunoprecipitation and immunoblotting. Somatic extracts from these two liver flukes as well as from other related parasites, together with the metabolic products, were tested for their reactivities with sera from patients with opisthorchiasis and clonorchiasis. A significant cross-reactivity in the ELISA was noted between Opisthorchis and Clonorchis. Immunoblotting and radioimmunoprecipitation analyses showed that the 89-kD protein which was previously shown to be a predominant metabolic product of O. viverrini reacted with sera from both groups of patients. However, an antigen with a molecular weight of 16 kD, apparently a predominant somatic component, appeared to be specific for O. viverrini. PMID- 2201721 TI - A dose-range finding study of zopiclone in insomniac patients. AB - Sixty insomniac patients participated in a controlled double-blind parallel group study designed to investigate the dose-response relationship of zopiclone. Following 1 day of treatment with placebo, patients were randomly assigned to 1 of 6 groups and received treatment for 7 days with either placebo, or flurazepam 30 mg, or zopiclone, 3.75 mg, 7.5 mg, 11.25 mg or 15 mg. Four patients were dropped from the study; two from the placebo group due to ineffectiveness and one each in zopiclone 11.25 mg and 15 mg groups due to side-effects. Flurazepam 30 mg significantly improved sleep induction and maintenance by comparison to placebo and was indistinguishable from zopiclone 7.5 mg or higher. Results of a self administered sleep questionnaire found a predominantly linear relationship between the dose of zopiclone administered and the degree of sleep improvement. The greatest increment in improvement was generally obtained with 3.5 mg and 7.5 mg of zopiclone, with some additional benefit occurring with zopiclone 11.25 mg. Clinicians' global impressions showed that the severity of illness clearly decreased in a dose related manner up to zopiclone 11.25 mg. Although zopiclone was well tolerated at 3.75 mg and 7.5 mg, an increase in side-effects occurred at 11.25 mg and 15 mg, which favours the use of 7.5 mg zopiclone as the optimum dose for most patients, although certain patients may benefit from a higher dose of the drug when well tolerated. PMID- 2201722 TI - Immediate and overnight effects of zopiclone 7.5 mg and nitrazepam 5 mg with ethanol, on psychomotor performance and memory in healthy volunteers. AB - The effects of ethanol (0.2-0.4 g/kg) taken in conjunction with a single nocturnal dose of zopiclone 7.5 mg or nitrazepam 5 mg, on the early morning performance were investigated by means of psychomotor tests in 9 female volunteers. While there was no noticeable difference in the Choice Reaction Time (CRT) for any of the drug-ethanol combinations and ethanol alone, the zopiclone combination appeared to be initially more sedative in the Critical Flicker Fusion test (CFF). Both drug combinations impaired short-term memory and induced retrograde amnesia to the same extent, although only the nitrazepam-ethanol treatment caused further anterograde amnesia as compared to ethanol alone. Finally, both drug-ethanol combinations exhibited equivalent hypnotic properties as assessed by the Leeds Sleep Evaluation Questionnaire (LSEQ) without any more residual effects than with ethanol alone. These results suggest neither zopiclone, nor nitrazepam potentiate the effects of ethanol at the doses used. PMID- 2201723 TI - A multi-centre open study in general practice to evaluate the efficacy and acceptability of zopiclone 7.5 mg nocte in patients requiring the prescription of an hypnotic. AB - This was an open study of the efficacy and acceptability of zopiclone 7.5 mg nocte as a somnifacient. The study population comprised 108 insomniac patients (70 female, 38 male) aged 22-74 years who received zopiclone 7.5 mg for 7 consecutive nights. Based on subjective sleep assessments, zopiclone reduced the patients' difficulty in falling asleep, increased the number of hours slept and decreased the number of nocturnal awakenings (p less than 0.001). The majority of patients reported sleeping well or very well. The quality of sleep improved (p less than 0.0001), and the incidence of waking earlier than desired decreased (p less than 0.001), with respect to baseline, after receiving zopiclone. Physicians rated efficacy as good or very good in the majority of patients. Zopiclone was efficacious both in patients who had not previously received hypnotic therapy (n = 37) and in patients who transferred directly to zopiclone from a benzodiazepine hypnotic (n = 26). Whilst receiving zopiclone, patients reported feeling better in the morning than they did prior to treatment (p less than 0.004); 78% expressing satisfaction with zopiclone as an hypnotic. Physicians reported zopiclone treatment to be without side-effects in the majority of patients. In conclusion, zopiclone appears to be an effective and well-tolerated hypnotic that may play a role in the treatment of insomnia in the general population. PMID- 2201724 TI - Actions and interactions of hypnotics on human performance: single doses of zopiclone, triazolam and alcohol. AB - Actions and interactions with ethanol (0.8 g/kg) of triazolam (TRZ, 0.25 mg) and zopiclone (ZOP, 7.5 mg) on performance and memory were studied with 12 healthy young subjects. The randomized double-blind and crossover test sessions were carried out at 1-week intervals. Each time a set of performance tests and self assessments on visual analogue scales were done before the treatment and 1.5, 3, 4.5, 6 and 8 h after it. The clinical test for drunkenness (CTD) was done 2 and 5 h after drug intake. Venous blood was sampled after each set of tests. Both TRZ and ZOP impaired coordinative and reactive skills, but not peripheral attention or body balance. They also impaired cognitive test performance (digit substitution, symbol copying), and lowered flicker fusion threshold. The psychomotor effects of the two hypnotics and measures of subjective sedation peaked at 1.5 and 3 h. Spatial memory was impaired by TRZ at 4.5 h. Cognitive tests and tracking were most sensitive to alcohol. Furthermore alcohol impaired both motor and vestibular aspects of the CTD while both ZOP and TRZ alone had only minor effects. Alcohol enhanced and prolonged the effects of both hypnotics without modifying their plasma concentrations. Drug-alcohol interactions were mainly additive though more obvious with TRZ. Interactions were evident also on the CTD. The hypnotics were free from residual psychomotor and cognitive effects at 8 h even after the coadministration of alcohol. It is concluded that ZOP and TRZ have a mainly additive interaction with alcohol but pharmacokinetic mechanisms do not seem to contribute essentially to this. PMID- 2201725 TI - Post marketing surveillance of zopiclone: interim analysis on the first 10,000 cases in a clinical study in general practice. AB - The tolerance of zopiclone, a hypnotic belonging to a new chemical group, the cyclopyrrolones, was studied in a follow-up trial in 23,000 insomniac outpatients treated for 3 weeks. The results from the interim analysis of the first 10,000 cases confirm the efficacy and safety of zopiclone under usual prescribing conditions. The average daily dose of zopiclone was 0.97 +/- 0.21 tablet (7.275 +/- 1.575 mg). The study population included 63.1% of female and 36.9% of male patients; the mean age was 52.3 +/- 16.6 years. 93.1% of the patients completed the trial. 8.2% of the patients experienced adverse reactions which resulted in drug discontinuation in only 2.8% of cases. In the global evaluation, the efficacy was rated excellent or good in more than 80% of the patients. PMID- 2201726 TI - Zopiclone, the third generation hypnotic: a clinical overview. AB - Effective and safe hypnotics exist especially since the introduction of benzodiazepines (BZD) which appeared to bring major advantages over barbiturates. Ideally a new hypnotic should induce and maintain sleep without producing residual effect during the day and should be devoid of abuse and dependence potential. Zopiclone is a new hypnotic belonging to the cyclopyrrolone chemical class. Its elimination half-life is 5 to 6 h, no accumulation exists upon repeated administration, and its pharmacokinetic profile is not substantially modified in elderly and renal failure patients. Placebo-controlled studies have shown that zopiclone 7.5 mg is an effective hypnotic, and that it can improve all sleep variables in insomniacs. Its effects on sleep stages differ from those observed with BZD hypnotics: REM sleep is substantially unaffected by zopiclone and slow wave sleep is either unaffected or increased. Objective and subjective measurements during the day after bedtime administration of zopiclone, showed lack of residual effects and no residual impairment of cognitive functions. Zopiclone discontinuation is not accompanied by rebound effect and relevant withdrawal symptoms. Specific "craving effect" studies in alcoholics did not show an abuse potential for zopiclone. Side-effects are represented mainly by bitter taste and dry mouth with a minimal incidence of CNS depressant effects. Studies on the effects of zopiclone on respiratory functions failed to show detrimental effects. Efficacy and safety data on zopiclone suggest that this new drug can represent a useful alternative to existing hypnotics. PMID- 2201727 TI - A comparative study of zopiclone and triazolam in patients with insomnia. AB - Zopiclone, a cyclopyrrolone derivative, was compared with triazolam in a double blind, randomized, parallel group study in general practice patients suffering from insomnia. Both drugs were found to be effective compared to baseline assessment in that they increased the number of hours of sleep, reduced the number of nocturnal wakenings and reduced the latency of falling asleep. In addition, both drugs improved patients' condition following awakening, with zopiclone showing slight superiority. In both treatment groups, there was a transient period of poor sleep after withdrawal of the drug, and one patient in each group withdrew from the study for this reason. There were no serious adverse reactions during the trial. PMID- 2201728 TI - A comparison of the efficacy, safety and withdrawal effects of zopiclone and triazolam in the treatment of insomnia. AB - A double-blind study comparing zopiclone and triazolam, in 48 healthy, chronic insomniacs, was undertaken in two centers to compare the hypnotic and withdrawal effects of both compounds. Comparable doses of 7.5 mg zopiclone and 0.25 mg triazolam were given at bedtime for 21 nights after a 3 day wash-out period, followed by 4 placebo nights of withdrawal monitoring. During the investigation, a 17 item post-sleep questionnaire was completed daily, the Clinical Global Impression (CGI) scale weekly, and the Hamilton Anxiety Scale (HAM-A) at baseline and at the end of the study. Withdrawal effects were evaluated with a withdrawal symptom checklist and the CGI (withdrawal). Results indicated that both compounds improved sleep and were equally effective. However, a larger number of triazolam subjects withdrew from the study because of ineffectiveness or adverse side effects. A greater number of zopiclone subjects experienced a transient modification of taste which disappeared with discontinuation of therapy. Significant deterioration in nearly all sleep parameters were noted after the first withdrawal night of triazolam; much fewer modifications of sleep parameters were observed following the discontinuation of zopiclone. PMID- 2201729 TI - Efficacy and safety of zopiclone and triazolam in the treatment of geriatric insomniacs. AB - Most studies with zopiclone, a cyclopyrrolone derivative with a short elimination half life (5 h) have compared its hypnotic activity with that of long elimination half life molecules. In this double-blind study in geriatric patients, drugs were administered during 3 weeks and the therapeutic effects of zopiclone at optimal dosage (5 or 7.5 mg) were compared to those of triazolam (0.125 or 0.25 mg). After a 3 day single-blind washout period, placebo responders were excluded and 48 patients were thereafter treated with either placebo (Tetreault et al., 1965), zopiclone or triazolam (Pegram et al., 1980). The initial dosage was increased when indicated at the end of the first week and kept constant thereafter. At the end of the third week of double-blind treatment, a 4 day single-blind placebo washout was performed to assess drug withdrawal effects. Results confirmed the safety and efficacy of both drugs over placebo during active administration. Hypnotic activity was maximal at 7.5 mg of zopiclone and 0.25 mg of triazolam. Drug efficacy was found constant over the 3 week administration both for triazolam and zopiclone. During withdrawal, no true rebound effect was demonstrated but the active drugs were significantly worse than placebo during the first day for sleep onset duration, sleep soundness and quality of sleep. With triazolam some effects persisted up to the third day of withdrawal. PMID- 2201730 TI - Zopiclone versus triazolam in insomniac geriatric patients: a specific increase in delta sleep with zopiclone. AB - This double-blind study was performed on 10 aged insomniac patients who received, during 15 days, either triazolam (0.25 mg) or zopiclone (7.5 mg) at bed time. This in-patient period was bounded by two ambulatory periods of 5 days each, and two in-patient periods of 3 days each, during which the patients received a placebo tablet at bed time. Thirteen sleep recordings per patient were performed before (3 nights), upon initiation of active treatment (3 nights), at the end of the active treatment period (3 nights) and during the following 3 "withdrawal" nights. A clear improvement of sleep patterns was observed with both drugs, although opposite effects on delta sleep were observed, namely a decrease with triazolam and an increase with zopiclone. A carry-over effect of the enhancement of delta sleep by zopiclone took place during the first 3 withdrawal nights. As is well known, sleep problems become increasingly common with age. Epidemiological studies show that although they only represent 11% of the population. Americans over 60 years old are prescribed about 40% of sleeping pills (Mendelson, 1980). Disturbed sleep in this population is often associated with medical disorders or induced by drugs like beta-adrenergic blockers. It must be admitted, however, that, possibly due to the association with medical or situational problems there have been only few attempts to assess the efficiency of hypnotic drugs in elderly insomniac patients. These are the reasons why in this study the effectiveness of zopiclone was compared to that of triazolam in insomniac patients aged over 60 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2201731 TI - A comparison of the efficacy, tolerance and residual effects of zopiclone, flurazepam and placebo in insomniac outpatients. AB - A double-blind randomized parallel group design was used to compare the tolerance and efficacy of zopiclone 7.5 mg, flurazepam 30 mg and placebo taken each night for 3 weeks in a group of 24 out-patients complaining of sleep disturbance. Analogue rating scales were used to assess the efficacy of the treatments while tolerance and residual effects were measured weekly using a battery of performance tests (Critical Flicker Fusion Threshold, Choice Reaction Time, Letter Cancellation and Digit Span). Physical and clinical examinations, including ECG and EEG, were conducted before and after the experimental period and spontaneously reported side-effects were recorded. Analysis of variance on 24 completed cases (8 patients in each treatment group) showed both active treatments to be significantly better than placebo in shortening sleep onset latency. Flurazepam increased the duration of sleep and produced a "hangover" of impaired psychomotor function. Zopiclone had no observable effect on early morning performance and was free from residual sedative activity. The lack of residual effects with zopiclone 7.5 mg, at a dose shown to be clinically effective, suggests its use in ambulant or out-patient populations where daytime sedation could interfere with every day activities. PMID- 2201732 TI - The effect of zopiclone 7.5 mg on the sleep, mood and performance of shift workers. AB - Shift workers often complain of an inability to sleep well between successive periods of work. The purpose of the study was to assess the influence of zopiclone, hypnotic with minimal residual effects, on work-time performance and mood. In this double-blind, cross-over study, 12 healthy male volunteers, aged between 18 and 35 years, from the Royal Air Force, working 12 h shifts in radar installations, were given zopiclone 7.5 mg at bed time or placebo for 2 shift cycles in a randomized order. Zopiclone significantly improved night time sleep, with a trend towards improvement of day-time sleep. There was no effect on psychomotor performance (assessed by critical flicker fusion threshold, choice reaction time and digit symbol substitution test) nor on mood (assessed by visual analogue scales). It can be concluded that zopiclone is a safe hypnotic which can be used by shift workers without impairing work time performance. PMID- 2201733 TI - Comparative study of the effects of zopiclone and placebo on respiratory function in patients with chronic obstructive respiratory insufficiency. AB - Long-term administration of zopiclone in 6 patients with severe chronic obstructive respiratory insufficiency with stable ventilatory function did not demonstrate any depressant action on respiratory blood gases recorded during the daytime and in ambient air. The sedative action of this agent was manifested by a modest decrease in ventilatory response parameters which, however, was not statistically significant. Polysomnographic recordings did not reveal any worsening of desaturation periods both with respect to incidence and amplitude. There was a non-significant trend towards an increase in the number of obstructive apnoea episodes without any notable ventilatory impact. PMID- 2201734 TI - Degeneracy theory, eugenics, and family studies. Essay review. PMID- 2201735 TI - Ultrastructural cytochemistry of the mammalian cell nucleolus. AB - In the present review on the organization of the mammalian cell nucleolus, we report and discuss data obtained during the past 10 years by means of cytochemical and immunocytochemical ultrastructural techniques. Particular emphasis is placed on the following topics: location of the nucleolus organizer regions in interphasic nucleolar components, structure of nucleolar chromatin in situ, and the structure-function relationship of the nucleolar components. The cytochemical and immunocytochemical results are compared and the concordant data are stressed for each topic. PMID- 2201736 TI - Mechanisms and products of azo coupling in histochemical protease procedures based on primary aromatic amines as unspecific moieties. AB - It is presumed that the azo dyes generated by histochemical protease reactions are formed by substitution of a reactive aromatic carbon. They are referred to as dyes of the C-azo series. To confirm this assumption, the absorption spectra between 330 and 630 nm of azo dyes resulting from coupling between various aromatic amines of the aniline and naphthylamine series and the diazonium salts Fast Blue B and Fast Garnet GBC were studied in test tube experiments. Some of the amines were blocked by methylation to prevent coupling either at the amino group (N-methylated) or at the aromatic nucleus (C-methylated). Coupling was performed in buffered aqueous solutions of the diazonium salts. For analysis the azo dyes were dissolved in dimethylformamide. For acid rearrangement these solutions were acidified and incubated at elevated temperatures. After detection of dipeptidyl peptidase IV in tissue sections using Gly-Pro-4-methoxy-2 naphthylamine as substrate, the resulting dye was extracted and compared with the test tube compounds. All aromatic amines yielded azo dyes. Dyes extracted from sections and those test tube compounds derived from unmethylated or C-methylated amines showed almost identical spectral maxima, whereas dyes formed by N methylated amines yielded different spectra. Acid rearrangement did not influence the spectral maxima of the N-methylated amine-derived dyes. Dyes resulting from C methylated amines were destroyed. The results indicate that under histochemical conditions diazonium salts react primarily with the liberated free amino group but not with the aromatic nucleus of the unspecific moiety. Therefore, it is proposed that the formula of the final reaction product in naphthylamine-based protease histochemistry should be given as an N-azo dye, e.g., as a triazene. PMID- 2201737 TI - Localization of cathepsin B in two human lung cancer cell lines. AB - We demonstrated the cysteine proteinase cathepsin B in two human lung tumor cell lines by cytochemical and immunocytochemical methods. The cell lines were derived from a squamous cell carcinoma of the lung (HS-24) and a metastasis to the adrenal gland from an adenocarcinoma of the lung (SB-3). For comparison and control, normal human lung fibroblasts cells (Wi-38) were also investigated. Intracellular cathepsin B activity was detected in all three cell lines. SB-3 and the normal fibroblast cells showed almost equal cathepsin B activity, which was considerably stronger than that in the HS-24 cells. Specific inhibitors for cathepsin B (E64, leupeptin, antipain) suppressed its activity completely. Stefin A, the physiological cathepsin B inhibitor, was less effective; this might depend on its limited penetrability into living cells. Localization of the cathepsin B was performed by conventional immunofluorescence microscopy and laser scanning microscopy. With specific anti-cathepsin B antibodies, the enzyme was localized in HS-24, SB-3, and Wi-38 fibroblast cells within perinuclear granules representing the lysosomal compartment. In the SB-3 cells, we additionally localized a minor fraction of the enzyme bound to the plasma membrane in a speckled distribution, accessible to the antibodies from the outside. This direct demonstration of cathepsin B distribution supports biochemical data about the dual localization of the enzyme in tumor cells. It also supports the possibility of a direct involvement of cathepsin B in the degradation of the extracellular matrix, and thus a contribution of the enzyme in invasion and metastasis. PMID- 2201738 TI - Improved method for obtaining 3-microns cryosections for immunocytochemistry. AB - The following describes a modified technique for obtaining 3-microns sections for light microscopic level immunocytochemistry. By combining 20% sucrose with Tissue Tek OCT embedding compound in a ratio of 2:1, we produced a block that was suitable for cutting 3-microns sections on a conventional cryostat. The 3-microns sections were dramatically improved compared with 10-microns sections cut from tissue embedded in OCT alone, when viewed with both differential interference contrast microscopy (Nomarski optics) and indirect immunofluorescence. The method is simple, uses materials already available, and does not require training in a new technique. PMID- 2201739 TI - From the National Institute of Allergy and Infectious Diseases. Summary of the 25th United States-Japan Joint Conference on cholera and related diarrheal diseases. PMID- 2201741 TI - Population-based risk factors for neonatal group B streptococcal disease: results of a cohort study in metropolitan Atlanta. AB - To determine risk factors for neonatal group B streptococcal (GBS) disease, a cohort study was conducted in Atlanta of infants with invasive GBS disease during 1982 and 1983. Laboratory review detected 71 infants with early-onset disease (1.09 cases/1000 live births) and 37 infants with late-onset disease (0.57 cases/1000 live births). Compared with the 64,858 births in Atlanta in the same period, infants with early-onset GBS disease were more often black, less than 2500 g, and born to teenage mothers. A history of miscarriage increased a woman's risk of delivering an infant with early-onset disease. Black infants had 35 times the risk of late-onset disease that nonblack infants had. Thirty percent of early onset disease and 92% of late-onset disease could be attributed to black race, independent of other risk factors. Most case-mothers (96%) received prenatal care, suggesting that prevention strategies such as prenatal screening or maternal immunization could reach nearly all the population at risk. PMID- 2201740 TI - Outer membrane protein and lipopolysaccharide heterogeneity among Eikenella corrodens isolates. AB - Outer membrane protein (OMP) and lipopolysaccharide (LPS) phenotypic diversity among 27 oral and extraoral strains of Eikenella corrodens was assessed by SDS PAGE. Each strain exhibited one to three major protein bands in the 35- to 41.5 kDa range and one or two protein bands of lesser density in the 24.5- to 28-kDa range. Eleven OMP patterns were distinguished among the strains. While oral strains obtained from periodontally healthy and diseased subjects exhibited diverse OMP patterns, five of six strains from extraoral sites of infection expressed an identical OMP pattern. Comparison of the electrophoretic mobilities of LPS from these same strains revealed that E. corrodens LPS consists primarily of low apparent molecular mass forms. Sixteen different LPS phenotypes were differentiated among the strains, with no apparent correlation between LPS phenotype and clinical setting. Strains expressing the same OMP pattern frequently expressed variable LPS phenotypes and vice versa. Analysis of OMP or LPS pattern by SDS-PAGE may be useful in taxonomic and epidemiologic studies of E. corrodens. Additional studies assessing the potential influence of OMP composition on invasiveness of this organism appear warranted. PMID- 2201742 TI - Therapy for shigellosis. II. Randomized, double-blind comparison of ciprofloxacin and ampicillin. AB - Ciprofloxacin, 500 mg every 12 h, was compared with ampicillin, 500 mg every 6 h, both given for 5 days, in the treatment of 121 adult males hospitalized with severe shigellosis. Treatment was randomized and double-blinded. At the completion of treatment, there was resolution or marked improvement in symptoms in 57 (95%) of 60 ciprofloxacin-treated patients, 23 (88%) of 26 ampicillin treated patients infected with an ampicillin-susceptible strain of Shigella, and 15 (43%) of 35 ampicillin-treated patients infected with an ampicillin-resistant strain of Shigella (ampicillin-R group) (P less than .01, ciprofloxacin or ampicillin groups vs. ampicillin-R group). Bacteriologic failure was less common (P less than .025) in the ciprofloxacin group (0/60) than in the ampicillin (3/26, 12%) or ampicillin-R groups (5/35, 14%). Ciprofloxacin-treated patients had a mean of 29 stools during the study, compared with 46 for ampicillin-treated patients (P = .004). Thus ciprofloxacin seems to be an effective, and perhaps superior, alternative to ampicillin in treating patients with shigellosis. PMID- 2201743 TI - Neurovascular interactions in the dental pulp in health and inflammation. AB - The two key components in pulpal inflammation are microcirculation and sensory nerve activity. With advancement of techniques they can be measured simultaneously in the same tooth. Excitation of A-delta fibers seems to have an insignificant effect on pulpal blood flow (PBF), whereas C fiber activation causes an increase in PBF. This C fiber-induced PBF increase is caused by neurokinins, especially substance P, which is released from the C fiber nerve terminals. Manipulation of PBF has varying effects on sensory nerve activity. An increase in PBF causes excitation of both A-delta and C fibers via an increase in tissue pressure, whereas flow reduction has an inhibitory effect on A-delta fibers, but no discernible effect on C fiber activity. Understanding of this complex neurovascular relationship in the pulp, especially given the fact that the pulp is in a low compliance system, is prerequisite to more comprehensive characterization of pulpal inflammation. PMID- 2201744 TI - Treating acute pain: do's and don'ts, pros and cons. AB - The mechanisms of action of centrally and peripherally acting analgesics are reviewed. Therapeutic implications are cited. PMID- 2201746 TI - Retraction. In individual T cells one productive alpha rearrangement does not appear to block rearrangement at the second allele. PMID- 2201745 TI - The influence of time of hydrogen peroxide exposure on the adhesion of composite resin to bleached bovine enamel. AB - Standard sized cylinders of a small particle light-cured resin were bonded to the flattened labial surface of young bovine incisor teeth which had been previously subjected to four different treatments: (a) immersion in 35% hydrogen peroxide and etched with 37% phosphoric acid gel for 60 s, (b) immersion in saline and etched for 60 s, (c) etched for 60 s and immersion in hydrogen peroxide, and (d) etched for 60 s and immersion in saline. Two hydrogen peroxide and saline immersion periods were used, 5 and 30 min. Specimens were stored in water at 37 degrees C for 1 and 7 days before tensile and shear testing. A total of 256 teeth were used, 8 for each treatment group, each immersion period, and each water storage period for each test. Statistical analysis of the results indicated that there was a highly significant reduction in the adhesive bond strength of the resin when the enamel was exposed to hydrogen peroxide and that the reduction was, within the limits of this study, time dependent. The bond strength was unaffected by the etching order and the period of water storage. Scanning electron microscopic examination of randomly selected fractured peroxide-treated specimens indicated that the failure occurred primarily at the bonding resin enamel interface and that it was associated with areas of resin nonattachment and an alteration in resin quality. It is suspected that these changes were caused by the presence of residual peroxide or peroxide-related substances at or near the enamel surface. PMID- 2201748 TI - Distinct antibody specificities to a 64-kD islet cell antigen in type 1 diabetes as revealed by trypsin treatment. AB - Type 1 diabetes is associated with antibodies that immunoprecipitate a 64-kD islet cell membrane protein from detergent extracts of pancreatic islets. In this study we have determined whether mild trypsin treatment of islet membranes can release fragments of the antigen that bind antibodies in the serum of Type 1 diabetic patients. Partial tryptic proteolysis of [35S]methionine-labeled 64-kD antigen immunoprecipitated from detergent extracts of rat islets resulted in the formation of 50-, 40-, and 37-kD fragments. Similar sized fragments were recovered when sera from diabetic patients were employed to immunoprecipitate polypeptides solubilized by mild trypsin treatment of a particulate fraction of radiolabeled rat islets. Of 27 diabetic patients, 22 possessed antibodies to the 50-kD polypeptide and 21 to the 40- and 37-kD polypeptides. A positive association was found between 64k antibodies and antibodies to the 50-kD fragment but not between 64k antibodies and antibodies to the 40- or 37-kD fragments. Some 64k antibody negative patients possessed antibodies that efficiently immunoprecipitated the latter fragments. Serum from 25 of 27 (93%) diabetic patients immunoprecipitated at least one of the three tryptic polypeptides. One of 20 nondiabetic controls immunoprecipitated a 50-kD polypeptide and all controls were negative for antibodies to 40- and 37-kD fragments. Thus, Type 1 diabetes is associated with the presence of at least two antibody reactivities to distinct determinants of the 64-kD antigen, and some patients may possess antibodies to a cryptic epitope on the detergent-solubilized molecule. These data suggest that the detection of antibodies (present in 93% of patients) to epitopes on tryptic polypeptides of the 64-kD antigen may be of even greater diagnostic value for the onset of Type 1 diabetes than analyses of antibodies reactive with the intact 64-kD antigen. PMID- 2201747 TI - Involvement of a phospholipase D in the mechanism of action of granulocyte macrophage colony-stimulating factor (GM-CSF): priming of human neutrophils in vitro with GM-CSF is associated with accumulation of phosphatidic acid and diradylglycerol. AB - The generation of diradylglycerol (DRG) and phosphatidic acid (PdtOH) was investigated in neutrophils primed with granulocyte-macrophage colony-stimulating factor (GM-CSF). Mass accumulation of DRG and PdtOH was measured using reversed phase high performance liquid chromatography and thin layer chromatography, respectively. GM-CSF had no direct effect on the levels of PdtOH and DRG, but it increased PdtOH generation and the late phase of DRG accumulation in human neutrophils stimulated with FMLP. The elevation of the mass of PdtOH peaked approximately 100 s and clearly preceded that of DRG, which peaked at 150 s. The diacylglycerol kinase inhibitor R59022 enhanced the sustained increase in DRG but did not produce a parallel inhibition in PdtOH production. GM-CSF was without effect on the level of inositol 1,4,5-triphosphate [Ins(1,4,5)P3] and did not affect the liberation of Ins(1,4,5)P3 induced by FMLP. These findings exclude the involvement of the PtdIns(4,5)P2-specific phospholipase C/diacylglycerol pathway in the sustained phase of DRG accumulation. The early (30-s) appearance of PdtOH clearly suggests that GM-CSF enhanced FMLP receptor-linked phospholipase D (PLD) generation of PdtOH. PLD was assessed more directly by formation of labeled phosphatidylethanol (PEt) through PLD capacity of catalyzing a trans phosphatidylation in presence of ethanol. The formation of PEt associated with a concomitant decrease in PdtOH directly demonstrated that the mechanism by which GM-CSF enhances PdtOH production is activation of a PLD active on phosphatidylcholine. This study provides evidence that the mechanism of action of GM-CSF involves upregulation of PLD activity leading to enhanced generation of PdtOH and DRG in FMLP-stimulated neutrophils. These findings may provide the basis for several of the priming effects of GM-CSF. PMID- 2201749 TI - Evidence of widespread binding of HLA class I molecules to peptides. AB - We have tested the binding of HLA class I proteins to peptides using a solid phase binding assay. We tested 102 peptides, mostly derived from the HIV gag and HIV pol sequences. Most peptides did not bind to any class I protein tested. The pattern of binding among the three class I proteins tested, HLA-A2, -B27, and B8, was approximately 85% concordant. Further, all five of the known HIV-1 gag T cell epitopes detected by human CTL bound at least one class I protein. Binding of class I to the peptides could be detected either by directly iodinated class I proteins, or indirectly using monoclonal antibodies specific for class I. The binding to the plates could be blocked with MA2.1, which binds in the alpha 1 region of A2, but not by W6/32, which binds elsewhere. The data presented here show that binding of class I to peptides is specific, but that many peptides bind to more than a single class I protein. PMID- 2201750 TI - Metabolic, humoral, and cellular responses in adult volunteers immunized with the genetically inactivated pertussis toxin mutant PT-9K/129G. AB - PT-9K/129G, a nontoxic mutant of pertussis toxin (PT) obtained by genetic manipulation, has been shown in animal models to be a promising candidate for new vaccines against whooping cough. To assess the safety and the immunogenicity of PT-9K/129G in humans, a pilot study has been performed in adult volunteers. The protein was found to be safe, capable of inducing high titers of toxin neutralizing antibodies, and capable of generating immunological memory. In fact, vaccination caused an increase of cell-mediated response to PT, PT-9K/129G, S1 subunit, and B oligomer, indicating that memory T cells are induced by the vaccine. Since PT-9K/129G is mitogenic for T lymphocytes in vitro, it was investigated whether this activity is also present in vivo. No variation was observed in the proportion of T cells (CD3+), T helper cells (CD4+), and cytotoxic T cells (CD8+), as well as in that of other lymphoid populations, by FACS analysis. Interestingly, no thorough correlation was found between humoral and cellular responses. In one case, a very high cellular response was present in absence of detectable antibodies, suggesting that the antibody response, which is the only parameter measured in most clinical trials, may not give a complete picture of the response induced by a vaccine. PMID- 2201752 TI - Different cellular types in mesopontine cholinergic nuclei related to ponto geniculo-occipital waves. AB - The only mesopontine neurons previously described as involved in the transfer of ponto-geniculo-occipital (PGO) waves from the brain stem to the thalamus were termed PGO-on bursting cells. We have studied, in chronically implanted cats, neuronal activities in brain-stem peribrachial (PB) and laterodorsal tegmental (LDT) cholinergic nuclei in relation to PGO waves recorded from the lateral geniculate (LG) thalamic nucleus during rapid-eye-movement (REM) sleep. We constructed peri-PGO histograms of PB/LDT cells' discharges and analyzed the interspike interval distribution during the period of increased neuronal activity related to PGO waves. Six categories of PGO-related PB/LDT neurons with identified thalamic projections were found: 4 classes of PGO-on cells: PGO-off but REM-on cells: and post-PGO cells. The physiological characteristics of a given cell class were stable even during prolonged recordings. One of these cell classes (1) represents the previously described PGO-on bursting neurons, while the other five (2-6) are newly discovered neuronal types. (1) Some neurons (16% of PGO-related cells) discharged stereotyped low-frequency (120-180 Hz) spike bursts preceding the negative peak of the LG-PGO waves by 20-40 msec. These neurons had low firing rates (0.5-3.5 Hz) during all states. (2) A distinct cell class (22% of PGO-related neurons) fired high-frequency spike bursts (greater than 500 Hz) about 20-40 msec prior to the thalamic PGO wave. These bursts were preceded by a period (150-200 msec) of discharge acceleration on a background of tonically increased activity during REM sleep. (3) PGO-on tonic neurons (20% of PGO-related neurons) discharged trains of repetitive single spikes preceding the thalamic PGO waves by 100-150 msec, but never fired high-frequency spike bursts. (4) Other PGO-on neurons (10% of PGO-related neurons) discharged single spikes preceding thalamic PGO waves by 15-30 msec. On the basis of parallel intracellular recordings in acutely prepared, reserpine-treated animals, we concluded that the PGO-on single spikes arise from conventional excitatory postsynaptic potentials and do not reflect tiny postinhibitory rebounds. (5) A peculiar cellular class, termed PGO-off elements (8% of PGO-related neurons), consisted of neurons with tonic, high discharge rates (greater than 30 Hz) during REM sleep. These neurons stopped firing 100-200 msec before and during the thalamic PGO waves. (6) Finally, other neurons discharged spike bursts or tonic spike trains 100-300 msec after the initially negative peak of the thalamic PGO field potential (post-PGO elements, 23% of PGO-related neurons).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2201754 TI - Electron microscopic localization of immunoreactive enkephalinase (EC 3.4.24.11) in the neostriatum of the rat. AB - The fine structural distribution of the enzyme-neutral endopeptidase EC 3.4.24.11 (enkephalinase) was examined by immunoradioautography (using an iodinated monoclonal antibody) and peroxidase immunocytochemistry (using the same probe in nonradioactive form) in the neostriatum of the rat. At the light microscopic level, both techniques revealed a heterogeneous distribution of immunoreactive enkephalinase in the caudoputamen, characterized by the presence of patches of intense immunolabeling prominent against a relatively strong immunoreactive matrix, a pattern reminiscent of mu opioid receptors radioautographically labeled in the same region. Pilot experiments indicated that fixation of the brain with a mixture of 4% paraformaldehyde, 0.05% glutaraldehyde, and 0.2% picric acid did not modify the distribution and only slightly reduced the intensity of striatal enkephalinase antigenicity, provided that the post-fixation period did not exceed 1 hr. In the neostriatum of animals fixed according to this protocol, enkephalinase immunoreactivity was found by electron microscopic immunoradioautography to be exclusively confined to neuronal and glial membrane interfaces. Immunoperoxidase cytochemistry confirmed the association of immunoreactive enkephalinase with the plasma membrane of neurons and, to a lesser extent, of astrocytes and oligodendrocytes. Both immunoradioautographic and immunoperoxidase techniques revealed a predominant association of the enzyme with neuronal perikarya and dendrites. The morphological features of the labeled perikarya, together with the presence of immunoreactive dendritic spines, suggested that some of these neurons corresponded to striatofugal medium spiny neurons. Immunoreactive enkephalinase was also detected at the level of myelinated and unmyelinated axons and axon terminals. These axons could potentially have originated from intrinsic striatal neurons or from the substantia nigra. Statistical analysis of silver grain distribution in electron microscopic immunoradioautographs indicated that immunoreactive enkephalinase was not preferentially concentrated at the level of specific membrane interfaces, but rather, was more or less uniformly distributed on the surface of neurons and/or glial cells. A similarly diffuse localization of the enzyme was apparent in peroxidase-reacted material, though the latter technique also revealed a microheterogeneity in the deposition of the reaction product along the labeled membranes. Finally, quantitative analysis of immunoradioautographs clearly indicated an absence of enkephalinase enrichment at the level of synaptic junctions. The similarity between the light and electron microscopic distribution of enkephalinase observed in the present study, and that previously reported for mu opioid receptors, lends support to the concept that this ectoenzyme may be involved in the inactivation of endogenous opioids in the mammalian neostriatum. PMID- 2201753 TI - Alpha-internexin, a novel neuronal intermediate filament protein, precedes the low molecular weight neurofilament protein (NF-L) in the developing rat brain. AB - alpha-Internexin is a 66 kDa protein that copurifies with intermediate filaments (IF) from rat spinal cord and optic nerve. This protein is axonally transported in rat optic nerve along with the neurofilament triplet proteins in slow component a. Polymerization in vitro and distribution in vivo confirm that alpha internexin is a neuronal IF. We raised 2 highly specific monoclonal antibodies to alpha-internexin which were applied to frozen rat brain sections and Western blots of cytoskeletal extracts. These results indicate that alpha-internexin is primarily an axonal protein found in most, if not all, neurons of the CNS. Immunoreactive proteins of similar molecular weight were found in cytoskeletal extracts of CNS tissue from several additional species, including mouse and cow. While the distribution of alpha-internexin as given by immunocytochemical methods is similar to that of low molecular weight neurofilament protein (NF-L) in the adult, its distribution in the embryo is far more extensive. At embryonic day 16, when the expression of NF-L is still limited to a relatively small number of cells and levels of expression are low, alpha-internexin is already found at much higher levels and in cells not yet expressing NF-L in detectable quantities. Similar results are found at embryonic day 12. These data suggest that neuronal IF in the developing nervous system contain a higher proportion of alpha internexin than their adult counterparts, and that expression of alpha-internexin precedes that of NF-L in many or most neurons of the developing brain. PMID- 2201751 TI - Cloning and characterization of cDNAs for murine macrophage inflammatory protein 2 and its human homologues. AB - A cDNA clone of murine macrophage inflammatory protein 2 (MIP-2) has been isolated from a library prepared from lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and the nucleotide sequence determined. This cDNA was used to clone cDNAs for human homologues of MIP-2 from a library prepared from phorbol myristate acetate-treated and LPS-stimulated U937 cells. Two homologues were isolated and sequenced. Human MIP-2 alpha and MIP-2 beta are highly homologous to each other and to a previously isolated gene, human gro/melanoma growth stimulating activity (MGSA). These three human genes, MIP-2 alpha, MIP-2 beta, and gro/MGSA, constitute a sub-family within the cytokine family represented by platelet factor 4 and interleukin 8. PMID- 2201755 TI - Long term hemodialysis spondylarthropathy: an atlanto-occipital location. AB - A 41 years old patient on hemodialysis for 17 years with a clinical and radiological picture of osteoarticular beta 2 microglobulin amyloidosis, is presented. The patient had skeletal involvements, included cystic lesions of the left hip and both humeral heads and a C5/C6 spondylarthropathy. She had also associated carpal tunnel syndrome. Radiological exploration of the atlanto occipital articulation demonstrated destructive changes. Histology documented osseous and periarticular deposition of beta 2 microglobulin derived amyloid. This is an unusual location of destructive spondylarthropathy in a patient on chronic hemodialysis. PMID- 2201756 TI - The geometry of the adult canine proximal femur. AB - The canine is often used as a model to study functional bone adaptation after total hip replacement. To improve our understanding of the model, we defined the central tendencies and statistical variations in the cross-sectional geometry, angle of anteversion, and cervicodiaphyseal angle of the proximal femur in 15 adult male mongrel dogs and compared the results with published reports of the human femur. Numerous similarities in the cross-sectional geometry of the canine and the human femur were noted, supporting the use of the canine as a model. The two species differed in that the orientation of the principal axes in the proximal cross sections was not related to the angle of anteversion in the canine femur, whereas these angles are related in humans. In addition, the canine medullary canal is larger than the human medullary canal relative to the external dimensions of the femur, and hence the canine has relatively thinner cortical bone. This difference in femoral cross-sectional geometry may explain, in part, why the canine provides an accentuated model of bone loss in hip arthroplasty experiments. PMID- 2201758 TI - Modeling intestinal absorption and other nutrition-related processes using PSPICE and STELLA. AB - In summary, SPICE models are constructed by translating a highly organized biological system into a network diagram by using a disciplined, systematic method for converting flows through barriers and chemical reactions into branches in a network connecting the compartments in the tissue according to the identity of the flowing entities. The first step in building a simulation model is essentially the same as the first step in learning about the method. Simple mechanisms are mastered first; and then as proficiency and understanding of the system grow, these can be connected and elaborated to produce simulations more closely approximating the real complexity of the living system. Other methods exist that may be easier to deal with initially, but often they cannot be utilized as generally as SPICE owing to their inherent limitations. One program available on Apple machines that has a high degree of user friendliness is STELLA. We will make some brief comparisons here, since STELLA is often an easier way to get started in simulation and often perfectly adequate for smaller problems. PMID- 2201757 TI - Visualization of living terminal hypertrophic chondrocytes of growth plate cartilage in situ by differential interference contrast microscopy and time-lapse cinematography. AB - The functional unit within the growth plate consists of a column of chondrocytes that passes through a sequence of phases including proliferation, hypertrophy, and death. It is important to our understanding of the biology of the growth plate to determine if distal hypertrophic cells are viable, highly differentiated cells with the potential of actively controlling terminal events of endochondral ossification prior to their death at the chondro-osseous junction. This study for the first time reports on the visualization of living hypertrophic chondrocytes in situ, including the terminal hypertrophic chondrocyte. Chondrocytes in growth plate explants are visualized using rectified differential interference contrast microscopy. We record and measure, using time-lapse cinematography, the rate of movement of subcellular organelles at the limit of resolution of this light microscopy system. Control experiments to assess viability of hypertrophic chondrocytes include coincubating organ cultures with the intravital dye fluorescein diacetate to assess the integrity of the plasma membrane and cytoplasmic esterases. In this system, all hypertrophic chondrocytes, including the very terminal chondrocyte, exist as rounded, fully hydrated cells. By the criteria of intravital dye staining and organelle movement, distal hypertrophic chondrocytes are identical to chondrocytes in the proliferative and early hypertrophic cell zones. PMID- 2201759 TI - Effects of subgingival irrigation on bacteremia following scaling and root planing. AB - The purpose of this study was to determine the effects of professional subgingival irrigation, together with subsequent patient administered home marginal irrigation, on the incidence of bacteremia after scaling and root planing (Sc/RP). A total of 60 periodontal maintenance patients were assigned to either Group 1: subgingival irrigation, with 0.12% CHX and daily marginal irrigation with 0.04% CHX; Group 2: subgingival irrigation with 0.12% CHX and daily marginal irrigation with water; Group 3: subgingival and daily marginal irrigation with water; Group 4: Non-irrigation (control). Patients entered the study after receiving a thorough periodontal maintenance appointment including a complete examination, Sc/RP, and standard oral hygiene instruction. Blood samples were taken at the 3-month visit before and after Sc/RP. Microbiological culturing was done using the Septi-Chek system, selective and non-selective media. Results from 54 patients showed that bacteremia was detected prior to Sc/RP in 2 patients and after Sc/RP in 10 patients. No significant effect by treatment regimens on post Sc/RP bacteremia could be detected. The organisms isolated included Eubacterium lentum, Propionibacterium acnes, Streptococcus species, Neisseria species, Candida albicans, Staphylococcus species, and un-identified Gram negative rods. PMID- 2201760 TI - Effects of external tetraethylammonium ions and quinine on delayed rectifying K+ channels in mouse pancreatic beta-cells. AB - 1. The whole-cell and outside-out patch configurations of the patch-clamp technique were used to study the mechanisms of block produced by external tetraethylammonium ions (TEA+) and quinine on delayed rectifying K+ channels in mouse pancreatic beta-cells. 2. In whole-cell recordings, TEA+ blocks the delayed outward current (which reflects the activity of delayed rectifying K+ channels by greater than 85%) in a concentration-dependent manner. The block appeared to be 1:1 with a Kd of approximately 1.4 mM at a membrane potential of 0 mV. The value of Kd varied with the membrane potential and there was an e-fold increase for a 70 mV depolarization. 3. Single-channel recordings revealed that delayed rectifying K+ channels have a unitary conductance of 8.5 pS ([K+]1 = 155 mM; [K+]o = 5.6 mM) and a single-channel K+ permeability of 2.8 X 10(-14) cm3 s-1. 4. First latency histograms of channel openings during voltage pulses from -70 to 0 mV peaked after 4 ms. A reaction scheme involving two closed states adequately but not perfectly described the distribution of the first latencies. The openings of the channels were grouped in bursts and the distribution of the closed times required two exponentials with time constants of 2.0 and 13 ms, respectively. The distribution of the open times could be described by a single exponential with a time constant of 25 ms. 5. Channel block produced by TEA+ (1 mM) was associated with a 40% decrease of the single-channel current amplitudes and a reduction in single-channel K+ permeability to 1.9 X 10(-14) cm3 s-1 but did not measurably affect the single-channel kinetics suggesting that the blocking reaction is very rapid. 6. Quinine blocked the whole-cell delayed outward current in a concentration-dependent manner. Half-maximal inhibition was attained at approximately 4 microM and the binding appeared to be 2:1. 7. Single-channel recordings indicated that the inhibition produced by quinine (10 microM) resulted from a decrease in the duration of the openings to a mean value of 6.7 ms. The time constants for the distribution of the closures were increased by approximately 30%. Quinine did not affect the amplitude of the openings. The rate constant of the blocking reaction (kB) was 15 mM-1 ms-1 at 0 mV. PMID- 2201762 TI - Hypothermia therapy in the postanesthesia care unit: a review. AB - Seventy percent of all postoperative patients--over 14 million cases annually- suffer from hypothermia, which is caused by the combination of the anesthetics preventing thermal homeostasis and the cold operating room environment. Therapeutic goals are to treat shivering, prevent the severe discomfort of hypothermia, maximize rewarming rate to shorten PACU time, and maximize patient safety. Traditional warming therapies do not actively heat the patient nor do they prevent the continued loss of endogenously produced heat. Convective warming therapy is a new technology that clinical studies have demonstrated to be effective in preventing intraoperative or treating postoperative hypothermia. PMID- 2201761 TI - Block of ATP-regulated and Ca2(+)-activated K+ channels in mouse pancreatic beta cells by external tetraethylammonium and quinine. AB - 1. The whole-cell and outside-out patch configurations of the patch-clamp technique were used to investigate the effects of extracellular tetraethylammonium ions (TEA+) and quinine on both Ca2(+)-activated and ATP regulated K+ channels in mouse pancreatic beta-cells. 2. The Ca2(+)-activated K+ channel has a single-channel K+ permeability of 4.7 x 10(-13) cm3 s-1 when recorded with physiological ionic gradients. This value decreased to 2.9 x 10( 13) cm3 s-1 after addition of 0.3 mM-TEA+. 3. Two exponentials with time constants of 0.2 and 4.7 ms were required to describe the distribution of the channel openings suggesting that the Ca2(+)-activated K+ channel has at least two open states. The fast and slow components comprised 16 and 84% of the total number of openings respectively. 4. TEA+ caused a concentration-dependent decrease in the single-channel amplitude and open probability of the Ca2(+) activated K+ channel. A Kd for the reduction in the mean current of 0.14 mM was observed. The stoichiometry was approximately 1:1. 5. Quinine blocked the Ca2(+) activated K+ channel in a concentration-dependent manner. Half-maximal block was observed at 0.10 mM and binding was 1:1. Inhibition by 20 microM-quinine was not associated with a decrease in channel amplitude but markedly reduced the lifetime of the channel openings. Two exponentials, with time constants of 0.5 and 1.3 ms, were required to describe the channel openings. The rapid component contained 55% of the events. 6. TEA+ reduced the single-channel amplitude of the ATP-regulated K+ channel in a concentration-dependent manner. Kd for the block was 22 mM and the binding approximately 1:1. The block was not associated with changes in the open probability or channel kinetics. Two exponentials were required to describe the distribution of the open times. The time constants for the fast and slow components were approximately 2 and approximately 20 ms respectively. The rapid component accounted for approximately 35% of the events. 7. Quinine (10-20 microM) almost abolished activity of the ATP-regulated K+ channels. Inhibition was characterized by slow onset and reversibility but not associated with a change in the appearance of the single-channel events. Quinine-induced block could not be reversed by diazoxide. 8. We conclude that TEA+ produces rapid block of both Ca2(+)-activated and ATP-regulated K+ channels.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2201763 TI - [alcohol and pregnancy: what is the level of risk?]. AB - A large number of congenital disorders are due to alcohol consumption during pregnancy. These anomalies are also known as the "fetal alcohol syndrome". Data available on this subject is very important and leaves no doubt in the disastrous effects of prenatal alcohol intake. Babies born with fetal alcohol syndrome present constant characteristics such as pre and post natal growth retardation, cranio-facial dysmorphism and central nervous system abnormalities. The mechanism by which alcohol produces these defects are linked to: 1. The alteration of essential aminoacid transfer. 2. Fetal hypoxia. 3. Central nervous system cellular proliferation and differentiation inhibition (mainly in the cerebellum and hippocampus). 4. Auto-immune reaction to S-100 protein. 5. Hormonal dysfunction. 6. Postnatal inhibition of response to growth hormones. The major risk is undoubtfully the excessive daily alcohol intake (2-6 consumptions/day). Social type of alcohol consumption brings more discrete effects and often these happen much later. Low birth weight and mental retardation may be seen with the absorption of 15 ml of alcohol per day (1 beer or 1 glass of wine or 40 ml of liquor) 52 mg/100 ml of blood alcohol has been identified as the fetal threshold activity concentration, while 140 mg/100 ml is associated with evident teratogenicity. Other factors such as maternal age and genetic predisposition also add to the risks of prenatal alcohol exposure. PMID- 2201764 TI - [Multiparametric bibliometric analysis of 15 years of international research in chemical toxicology. 1: general presentation and descriptive analysis]. PMID- 2201765 TI - [Methods of in vitro evaluation for nephrotoxicity]. AB - Mechanisms and precise targets of nephrotoxicants have been evidenced in experimental animals, a very important contribution for decades. But, structural and functional heterogeneity in renal tissue makes often difficult the exact determination of the molecular targets at renal cell level. Indeed, some new in vitro models have been gradually reported. This non exhaustive review purposes to present the different recent models, ever more reductionist, as isolated kidneys, kidney slices, isolated renal cells or renal cultured cells to assess the nephrotoxicity of new molecules. For every model are presented a brief history, the principle of the technique, viability criteria and its relative interest for renal toxicology. In conclusion, a general discussion points out the main advantages and limits of each one. PMID- 2201766 TI - Side effects from studying for examinations. PMID- 2201767 TI - Comparative study of adjuvant induced arthritis in susceptible and resistant strains of rats. II. Effect of oral administration of BCG and PPD. AB - In rats of the Holtzman strain, susceptible to the development of adjuvant induced arthritis (AIA), oral administration of BCG significantly inhibited the development of the disease. Oral treatment with purified protein derivative (PPD) had no effect. In the resistant Buffalo rats, however, oral administration of BCG and PPD enhanced the lesions. Since oral administration of antigens has been described to induce suppressor cells, our results suggest that the development of AIA is controlled by suppressor mechanisms, which fail to be activated in the susceptible strain, but are stimulated by the oral administration of BCG. PMID- 2201768 TI - Effect of Plasmodium falciparum on the survival of naturally infected afrotropical Anopheles (Diptera: Culicidae). AB - The effect of the malarial parasite, Plasmodium falciparum Welch, on the daily survival rates and longevity of Anopheles gambiae Giles sensu lato and Anopheles funestus Giles was determined for wild-caught, naturally infected females from western Kenya. Mosquitoes were collected inside houses and held in cages until death, after which they were assayed for P. falciparum circumsporozoite protein by an enzyme-linked immunosorbent assay (ELISA). Survival rates of field populations determined by parity rates were significantly higher than survival rates estimated by regression for Anopheles dying in cages. Overall, An. gambiae s.l. had a significantly higher daily mortality rate (means = 17.5%) than An. funestrus (means = 13.2%). P. falciparum ELISA infection rates, which were higher for An. gambiae s.l. (means = 19.8%; n = 1,221) than for An. funestus (means = 11.9%; n = 1,128), did not increase as a function of time for caged Anopheles. For An. gambiae s.l., there was a significant negative correlation between holding time and P. falciparum ELISA absorbance, suggesting that detectable circumsporozoite protein and perhaps the number of sporozoites may decrease with time in the vector. In western Kenya, an area where Anopheles populations often have extremely high malaria infection rates. Plasmodium infections did not reduce vector survivorship. PMID- 2201769 TI - Records of ectoparasites on humans and sheep from Viking-age deposits in the former western settlement of Greenland. AB - During recent archaeological excavations in Viking Greenland, specimens of the human flea, Pulex irritans L., and the body louse, Pediculus humanus humanus L., were recovered from several farmsteads. Bovicola ovis (Schrank) and the sheep ked, Melophagus ovinus (L.), also were found in associated deposits. The specimens were dated from about AD 990 to AD 1350. These finds raise questions about the levels of hygiene of the Viking farmers and open some interesting medical and biogeographical conundrums. PMID- 2201770 TI - Larvae of the woodrat fleas Anomiopsyllus amphibolus and Atyphlocerus echis echis (Siphonaptera: Hystrichopsyllidae). AB - The external morphology of Anomiopsyllus amphibolus Wagner, 1936 and Atyphloceras echis echis Jordan and Rothschild, 1915 larvae (Siphonaptera: Hystrichopsyllidae) from woodrat (Neotoma lepida) nests is described. Among known flea larvae, the genus Anomiopsyllus (Anomiopsyllinae, Anomiopsyllini) is as distinctive in larval form as are the adults. Among other distinctive features, only Anomiopsyllus are known to have only two ventrolateral setae. Atyphloceras (Hystrichopsyllinae, Hystrichopsyllini) larvae seem more similar in morphology to those of Typhloceras (Hystrichopsyllini) than to Hystrichopsylla, the other genus placed within the Hystrichopsyllini. Characters used to distinguish flea larvae found in Neotoma nests are discussed. PMID- 2201771 TI - Interpretation of low-level Plasmodium infection rates determined by ELISA for anophelines (Diptera: Culicidae) from Egyptian oases. AB - Plasmodium infection rates determined by enzyme-linked immunosorbent assay (ELISA) were compared for Anopheles sergentii (Theobald) and An. multicolor Cambouliu in Siwa Oasis, Egypt, an area with low-level Plasmodium vivax transmission, and in Bahariya and Farafra, two other Egyptian oases which appear to be free of malaria. Initial testing indicated that 4.4% (23 of 518) and 0.8% (4 of 518) of the An. sergentii were positive for P. vivax and P. falciparum, respectively, and that 1.4% (1 of 71) of the An. multicolor were positive for P. falciparum. However, after two confirmational tests, only 1.2% (6 of 518) of the An. sergentii remained consistently positive for P. vivax. Initial ELISA absorbance was not a useful predictor of potential false positive reactions in the P. vivax assay. Paradoxically, the six ELISA-positive An. sergentii were from the two malaria-free oases. This study raises the question of whether ELISA positive reactions for anopheline vector species provides unequivocal evidence for transmission in areas of low malaria endemicity. PMID- 2201772 TI - United States government regulation of medical device software: a review. AB - A brief history of the regulation of medical device software within the United States is presented, along with a discussion of the reasoning that the US Food and Drug Administration (FDA) presents for modifying the requirements for software regulation from those previously used for hardware devices. The current regulatory status is discussed for the two categories of medical device software, software used within medical devices and software used to produce or test medical devices. The published FDA documents which determine the current environment for the regulation of software are summarized and discussed. The two types of medical device software are related to the two areas of FDA regulation, good manufacturing practices and permission to sell medical devices. The expected direction of future medical device software regulation, and its relationship to the European Economic Community (EEC) and international markets is discussed. PMID- 2201774 TI - Crystallization and preliminary X-ray studies of D-serine dehydratase from Escherichia coli. AB - Single crystals of D-serine dehydratase from Escherichia coli complexed with 3 amino-2-hydroxypropionate have been obtained from ammonium sulfate solution (pH 7.0) by vapor diffusion. The crystals belong to the trigonal space group P3(1) or P3(2) with a = b = 81.3 A and c = 58.4 A. The asymmetric unit cell contains one protein molecule with Mr = 48,289. The crystals diffract to at least 3.0 A resolution and are suitable for X-ray structure analysis. PMID- 2201773 TI - Biomechanical measurement of fracture healing. AB - Three techniques for measuring fracture healing are presented. These techniques are: (1) use of strain gauge measurements of the forces in an external fixator to determine fracture stiffness, (2) measurement of the vibration modes of a fractured long bone compared to the unfractured contralateral and (3) comparison of the ultrasound velocity across the fracture site with that for the normal unfractured bone. Examples of clinical results obtained using these techniques are presented, and the advantages and disadvantages of each technique are discussed. PMID- 2201775 TI - Deletion of sites for initiation of DNA synthesis in the origin of broad host range plasmid R1162. AB - The origin of replication of the broad host-range plasmid R1162 contains two, oppositely facing initiation sites for DNA synthesis. Either of these sites can be deleted from an R1162 plasmid derivative. However, the resulting plasmids are unstable, maintained at a lower copy-number in the cell, and form dimers and other recombinants that are required for propagation of the plasmid. In vitro, a derivative lacking one initiation site is deficient in synthesis of the strand normally initiated from that site. The properties of the intact origin are restored if it contains two oppositely facing sites; one initiation site may substitute for the other, and each site need not be in its original orientation. Overall, the results suggest that synthesis of each strand of R1162 DNA is initiated at a single site, and that there is no efficient system for initiation of lagging strand synthesis during transit of the replication forks. PMID- 2201776 TI - Precise mapping and comparison of two evolutionarily related regions of the Escherichia coli K-12 chromosome. Evolution of valU and lysT from an ancestral tRNA operon. AB - Two tRNA operons have been found near the gltX gene encoding the glutamyl-tRNA synthetase of Escherichia coli K-12. The alaW operon previously undetected from genetic data and containing two identical tRNA(GGCAla) genes is 800 base-pairs downstream from the gltX terminator and is transcribed from the same strand. The valU operon containing genes for three identical tRNA(UACVal) and one tRNA(UUULys) (the wild-type allele of supN), is adjacent to gltX and is transcribed from the opposite strand. Five open reading frames were also found in this region encoding putative polypeptides of 62, 105, 130, 167 and 294 amino acid residues. ORF294 is a new member of the lysR family of bacterial transcriptional activators. The possibility that this is the xapR gene is discussed. Comparison of the physical and linkage maps of the E. coli chromosome in the 52 minute region has permitted precise mapping of most of the 18 genes in this region with the order nupC-glk- less than (alaW beta-ala W alpha)-1 kb- less than gltX-0.3 kb-(valU alpha-valU beta-valU gamma-lysV = supN) greater than xapR xapA- less than lig-1 kb-cysK greater than -0.4 kb-ptsH greater than -0.05 kb pstI greater than -0.05 kb-crr greater than -cysM-cysA in the clockwise order (greater than and less than indicate the direction of transcription; kb, 10(3) bases). The last two genes of valU (52 min) and lysT (16.5 min) are arranged in a similar fashion and a highly conserved region has been found in both operons. This suggests that the valU and lysT operons probably arose by a duplication of an ancestral tRNA operon. This is the first example of what may be two different tRNA operons from the same organism evolving from an ancestral tRNA gene. Comparison of the 16 and 52 minute regions of the E. coli K-12 chromosome suggests that these two regions could share a common ancestor. PMID- 2201777 TI - Closely spaced and divergent promoters for an aminoacyl-tRNA synthetase gene and a tRNA operon in Escherichia coli. Transcriptional and post-transcriptional regulation of gltX, valU and alaW. AB - The transcription of the gltX gene encoding the glutamyl-tRNA synthetase and of the adjacent valU and alaW tRNA operons of Escherichia coli K-12 has been studied. The alaW operon containing two tRNA(GGCAla) genes, is 800 base-pairs downstream from the gltX terminator and is transcribed from the same strand. The valU operon, containing three tRNA(UACVal) and one tRNA(UUULys) (the wild-type allele of supN) genes, is adjacent to gltX and is transcribed from the opposite strand. Its only promoter is upstream from the gltX promoters. The gltX gene transcript is monocistronic and its transcription initiates at three promoters, P1, P2 and P3. The transcripts from one or more of these promoters are processed by RNase E to generate two major species of gltX mRNA, which are stable and whose relative abundance varies with growth conditions. The stability of gltX mRNA decreases in an RNase E- strain and its level increases with growth rate about three times more than that of the glutamyl-tRNA synthetase. The 5' region of these mRNAs can adopt a stable secondary structure (close to the ribosome binding site) that is similar to the anticodon and part of the dihydroU stems and loops of tRNA(Glu), and which might be involved in translational regulation of GluRS synthesis. The gltX and valU promoters share the same AT-rich and bent upstream region, whose position coincides with the position of the upstream activating sequences of tRNA and rRNA promoters to which they are similar. This suggests that gltX and valU share transcriptional regulatory mechanisms. PMID- 2201778 TI - Crystal structure of Escherichia coli thymidylate synthase containing bound 5 fluoro-2'-deoxyuridylate and 10-propargyl-5,8-dideazafolate. AB - The crystal structure of an Escherichia coli thymidylate synthase (TS) ternary complex containing 5-fluoro-2'-deoxyuridylate (FdUMP) and 10-propargyl-5,8 dideazafolate (PDDF) has been determined and refined at 2.3 A resolution. Each of the two chemically identical subunits folds into a three-layer domain anchored by a large six-stranded mixed beta-sheet. The backside of one sheet is juxtaposed against the corresponding face of the equivalent sheet in the second protomer creating a beta-sandwich. In contrast to other proteins of known structure in which aligned beta-sheets stack face to face with a counterclockwise rotation, sheets in the TS dimer are related by a clockwise twist. The substrate-binding pocket is a large funnel-shaped cleft extending some 25 A into the interior of each subunit and is surrounded by 30 amino acids, 28 from one subunit and two from the other. FdUMP binds at the bottom of this pocket covalently linked through C-6 to the sulfur of Cys146. Up-pointing faces of the pyrimidine and ribose rings are exposed to provide a complementary docking surface for the quinazoline ring of PDDF. The quinazoline inhibitor binds in a partially folded conformation with its p-aminobenzoyl glutamate tail exposed at the entrance to the active site cleft. Ternary complex formation is associated with a large conformational change involving four residues at the protein's carboxy terminus that close down on the distal side of the inhibitor's quinazoline ring, capping the active site and sequestering the bound ligands from bulk solvent. PMID- 2201779 TI - Stereochemical mechanism of action for thymidylate synthase based on the X-ray structure of the covalent inhibitory ternary complex with 5-fluoro-2' deoxyuridylate and 5,10-methylenetetrahydrofolate. AB - The structure of the Escherichia coli thymidylate synthase (TS) covalent inhibitory ternary complex consisting of enzyme, 5-fluoro-2'-deoxyuridylate (FdUMP) and 5,10-methylene tetrahydrofolate (CH2-H4PteGlu) has been determined at 2.5 A resolution using difference Fourier methods. This complex is believed to be a stable structural analog of a true catalytic intermediate. Knowledge of its three-dimensional structure and that for the apo enzyme, also reported here, suggests for the first time how TS may activate dUMP and CH2-H4PteGlu leading to formation of the intermediate and offers additional support for the hypothesis that the substrate and cofactor are linked by a methylene bridge between C-5 of the substrate nucleotide and N-5 of the cofactor. By correlating these structural results with the known stereospecificity of the TS-catalyzed reaction it can be inferred that the catalytic intermediate, once formed, must undergo a conformational isomerization before eliminating across the bond linking C-5 of dUMP to C-11 of the cofactor. The elimination itself may be catalyzed by proton transfer to the cofactor's 5 nitrogen from invariant Asp169 buried deep in the TS active site. The juxtaposition of Asp169 and bound tetrahydrofolate in TS is remarkably reminiscent of binding geometry found in dihydrofolate reductase where a similarly conserved carboxyl group serves as a general acid for protonating the corresponding pyrazine ring nitrogen of dihydrofolate. PMID- 2201780 TI - Need for uniformity in collection and reporting of data in cancer clinical trials. PMID- 2201781 TI - Experts debate quality of life as clinical trial endpoint. PMID- 2201782 TI - Oncogene mechanism suggests novel therapeutic approaches to cancer. PMID- 2201783 TI - A biochemical connection between ras, yeast, and cholesterol synthesis. PMID- 2201784 TI - Effects of UV radiation on tumor immunity. PMID- 2201785 TI - How toxic is 2,3,7,8-tetrachlorodibenzodioxin to humans? AB - The tissue levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) measured in different species are reviewed. Based on the correlation of tissue levels and a toxic response in different species, humans are less or no more susceptible to the toxic effects of TCDD than most of the laboratory animals that have been studied. Thus, the present exposure of the general population to environmental levels of TCDD are related compounds should not be of concern. PMID- 2201786 TI - Fibrin glue-antibiotic suspension in the prevention of prosthetic graft infection. AB - The following study was done to assess whether fibrin glue-antibiotic suspension (FGAS) can prevent infection of a PTFE vascular graft in a contaminated wound. METHODS: FGAS was made by combining cryoprecipitate with a mixture of bovine thrombin, aminocaproic acid, and tobramycin (5 mg/cc thrombus). Antibiotic activity was documented by in vitro kinetics which revealed initial elutions to be greater than 8,000 mu gm/cc and elutions at 4 days to be greater than 2 mcg/cc. Twelve dogs had a 1-cm section of infrarenal aorta replaced with a PTFE graft that had been bathed in a 2-cc solution of E. coli 3 x 10(8) CFU/ml and S. aureus 3 x 10(8) CFU/ml. Both organisms were sensitive to tobramycin and cefonicid. Dogs were divided into three groups of four. Group I had a contaminated PTFE graft placed and no further therapy. Group II had a contaminated PTFE graft placed and sealed with fibrin glue. Group III had a contaminated PTFE graft placed and sealed with FGAS. All three groups received daily IV cefonicid. RESULTS: Group I: Four of four dogs were reoperated on the fourth day for suspected sepsis and all four had pseudoaneurysms (one ruptured). Three of four were culture positive for S. aureus and two of four positive for E. coli. Group II: Four of four died of anastomotic disruption by the third day. Four of four were culture positive for S. aureus and E. coli. Group III: All four dogs survived and were sacrificed on Day 17: all anastomoses were normal. Animal survival was significantly associated with the treatment given (p = 0.0025). Three of four tissue cultures of the grafts were weakly positive for S. aureus and one of four for E. coli and Pseudomonas. Serum tobramycin levels were negligible at 12, 24, 72, and 96 hours. CONCLUSIONS: The data show that FGAS was associated with a reduction in vascular graft infection and pseudoaneurysm formation after exposure to a standardized bacterial inoculum. Whether complete eradication of all organisms can be achieved with higher doses of tobramycin is as yet undetermined. PMID- 2201787 TI - Packing and planned reexploration for hepatic and retroperitoneal hemorrhage: critical refinements of a useful technique. AB - We evaluated 35 consecutive patients treated with temporary intraabdominal packing for control of bleeding to determine factors that could improve hemorrhage control, morbidity from infection, and mortality. Twelve patients could not be resuscitated from hemorrhagic shock and died in the operating or recovery room. Bleeding was controlled in the remaining 23 patients; however, five (22%) died of complications other than hemorrhage. Intra-abdominal abscesses occurred in seven of the 21 patients who survived longer than 5 days and were more frequent in patients who had gastrointestinal perforation (50% versus 27%) and selective hepatic artery ligation (80% versus 19%). Four patients with either retrohepatic vena cava injury, hepatic vein injury, or both, were packed without attempted repair; three underwent delayed repair and survived. Coagulopathy occurred in 55% of patients who received greater than 15 units of blood before packing but in only 17% who received less than 15 units. The abdomens of ten patients were closed with a prosthetic mesh which did not prevent hemorrhage control, and only one patient developed a wound infection compared to 42% of patients with primary suture closure. We therefore conclude: 1) packing is more effective if instituted early (when less than 15 units of blood have been transfused) and is not contraindicated before either repair of retrohepatic vena cava injury, hepatic vein injury, or both; 2) selective hepatic artery ligation should be avoided if packing alone stops bleeding; 3) abdominal closure with a synthetic mesh decreases the incidence of wound infection; and 4) patients should be returned to the operating room for repacking if 24-hour postoperative blood requirements exceed 10 units. PMID- 2201788 TI - Untreated intra-abdominal sepsis: lack of synergism between polymorphonuclear leukocyte (PMN) complement receptors CR1/CR3 and IgG receptor FcRIII. AB - We have examined the effects of untreated intra-abdominal sepsis on polymorphonuclear leukocyte (PMN) phagocytosis. Phagocytosis was studied in a receptor-specific fashion looking at the interrelationship between FcRIII-, complement receptor (CR1)-, and complement receptor 3 (CR3)-mediated phagocytosis. Twelve swine underwent either sham laparotomy (n = 5) or laparotomy with cecal ligation and incision (n = 7) to induce intra-abdominal sepsis. PMN phagocytosis was assayed on POD 1, 4, and 8. In animals undergoing sham laparotomy, FcRIII-mediated phagocytosis was less than 10% on all days and was augmented with the addition of C3b or C3bi to the target particles (FcR + CR1 or FcR + CR3 greater than FcR alone). In animals undergoing cecal ligation and incision, baseline FcRIII-mediated phagocytosis increased between POD 1 and 4 and fell between POD 4 and 8. No increase in phagocytosis was seen on POD 4 or 8 with the addition of C3b or C3bi to the target particles (FcR + CR1 or FcR + CR3 = FcR alone). Preligation of the FcRIII but not FcRII or FcRI receptor with a monoclonal antibody (3G8) markedly reduced phagocytosis in the animals with intraabdominal sepsis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2201789 TI - Growth of melanocytes in human epidermal cell cultures. AB - Epidermal cell cultures were grown in keratinocyte-conditioned medium for use as burn wound grafts; the melanocyte composition of the grafts was studied under a variety of conditions. Melanocytes were identified by immunohistochemistry based on a monoclonal antibody (MEL-5) that has previously been shown to react specifically with melanocytes. During the first 7 days of growth in primary culture, the total number of melanocytes in the epidermal cultures decreased to 10% of the number present in normal skin. Beginning on day 2 of culture, bipolar melanocytes were present at a mean cell density of 116 +/- 2/mm2; the keratinocyte to melanocyte ratio was preserved during further primary culture and through three subpassages. Moreover, exposure of cultures to mild UVB irradiation stimulated the melanocytes to proliferate, suggesting that the melanocytes growing in culture maintained their responsiveness to external stimuli. When the sheets of cultured cells were enzymatically detached from the plastic culture flasks before grafting, melanocytes remained in the basal layer of cells as part of the graft applied to the patient. PMID- 2201790 TI - Computer-assisted drug prevention. AB - Although the psychological treatment of addiction is premised on the notion that addictive behavior is learned behavior, addiction workers have been slow to exploit the capacity of the computer to promote new learning. The best computer assisted learning programs are fully adaptive; their design anticipates the responses a user can make, classifies them, and provides feedback for each. This paper reports on two recent attempts to achieve this level of sophistication in computer-assisted drug prevention. One program seeks to prevent heroin relapse among currently abstinent prisoners, and the other promotes controlled drinking in alcohol abusers. Given the fact that most drug users can be expected to opt for self-help materials over the offer of formal therapy, and that most (licit) drug users who solve their addiction problems do so without recourse to professional help anyway, the use of computer-assisted drug prevention programs like these provides an important new direction in substance abuse treatment. PMID- 2201791 TI - Current status of tumor of the bowel following ureterosigmoidostomy: a review. AB - In the final analysis the major question that arises is whether urinary diversion to the intact colon should be performed at all for benign conditions in which a relatively long life expectancy may be anticipated. In answer to this question we believe that if exstrophy is the problem early primary closure with the staged reconstruction should be attempted first. If such efforts are marred by persistent incontinence management with an artificial urinary sphincter should be considered. In individuals with multiple bladder dehiscences after attempts at primary bladder closure, or in an individual with persistent incontinence despite multiple procedures surgical alternates should include diversion by a bowel conduit, continent urinary diversion, a variant of the ureterosigmoidostomy or standard ureterosigmoidostomy. Indeed, despite the appropriate concern regarding the development of tumor in ureterosigmoidostomy, this diversion may still have a major role in the educational process of urology throughout the next decade. Specifically, we must apply the knowledge gained from our clinical and laboratory investigations of ureterosigmoid diversion to the current more popular means of diversion. Of particular concern are the clinical findings of adenocarcinoma in enteric augmentations. This discovery must serve as a warning for the possibility of urocolonic tumors developing within alternative continent urinary diversions within the next 20 to 30 years. Certainly, at least annual evaluations of any diversions are mandatory until we can define accurately the morbidity and mortality arising from our interventional management. PMID- 2201793 TI - Experience with the Dornier HM4 and MPL 9000 lithotriptors in urinary stone treatment. AB - From November 17, 1987 until August 20, 1988 we operated a fluoroscopy guided Dornier HM4 kidney lithotriptor. This lithotriptor subsequently was replaced by the ultrasound guided Dornier MPL 9000 lithotriptor, a multipurpose machine for urinary and biliary stone treatment. With the Dornier HM4 device we performed 447 treatment sessions in 319 patients (483 stones). The mean number of shock waves was 1,848 per patient. The re-treatment rate was 1.17 per patient. After 3 months 85% of the patients were free of stone. Auxiliary procedures were performed in 27.6% of the sessions. From September 20, 1988 until August 30, 1989 we used the Dornier MPL 9000 lithotriptor on 246 patients with 407 stones in 354 treatment sessions. The mean number of shock waves per session was 1,654 per patient, 1.11 treatments were performed per patient and the rate free of stones after 3 months was 85%. Auxiliary measures before and after lithotripsy were performed in 33.6% of the sessions. The experience with both of these machines is discussed in regard to performance, as well as the specific advantages and disadvantages of the different imaging systems. PMID- 2201792 TI - Preparative cytoreductive surgery in patients with metastatic renal cell carcinoma treated with adoptive immunotherapy with interleukin-2 or interleukin-2 plus lymphokine activated killer cells. AB - A total of 63 patients with metastatic renal cell carcinoma with the primary kidney tumor in place was accepted as candidates for immunotherapy at the Surgery Branch of the National Cancer Institute. Of the 63 patients 54 underwent nephrectomy and 9 were treated with the primary kidney tumor in place. Many of the patients underwent associated procedures, such as regional lymphadenectomy (11), venacavotomy with extraction of tumor thrombus (9), hepatic resection (2), pulmonary wedge resection (2), cholecystectomy (2), splenectomy (2), distal pancreatectomy (1), omentectomy (1) and contralateral adrenalectomy (1). Of the 54 patients 20 were not able to enter therapy because of tumor-related (17) or other medical (3) reasons that developed between the operation and therapy, while 34 were able to receive immunotherapy postoperatively. The 20 patients who were treated with either high dose interleukin-2 or interleukin-2 plus lymphokine activated killer cells soon postoperatively (mean 2.1 months) were able to tolerate roughly the same amount of interleukin-2 as the 74 who had undergone nephrectomy before referral to our institute and who were treated for a mean of 22 months after nephrectomy. Further studies, including a prospective, randomized trial, will be required to define the role of nephrectomy in patients with advanced renal cell carcinoma before treatment with interleukin-2 based immunotherapies. PMID- 2201794 TI - Low dose intravesical heparin as prophylaxis against recurrent noninvasive (stage Ta) bladder cancer. AB - A controlled randomized clinical trial was conducted to examine the efficacy of topical low dose heparin (0.125 gm./l., 25,000 units per l.) as prophylaxis against recurrent noninvasive (stage Ta) transitional cell bladder cancer. Transurethral tumor resection was done with irrigation fluid containing either 1.5% glycine with heparin or glycine solution alone. Tumor recurrence was determined by cystoscopy 4 to 6 months later. There were 70 patients evaluated: 38 in the heparin and 32 in the control group, respectively. The recurrence rate (heparin 74%, control 66%) and the median number of recurrences (heparin 3, range 1 to 15 and control 3, range 1 to 30) were similar (p greater than 0.05) in the 2 groups of patients. These observations show that low dose heparin administered in the irrigation fluid during transurethral resection does not decrease the recurrence rate of noninvasive (stage Ta) bladder cancer. PMID- 2201795 TI - A randomized controlled study of intravesical alpha-2b-interferon in carcinoma in situ of the bladder. AB - We treated 87 patients with carcinoma in situ of the bladder in a prospective randomized trial of 2 dose levels of intravesically administered alpha-2b interferon. Patients received either low dose (10 million units) or high dose (100 million units) recombinant alpha-2b-interferon weekly for 12 weeks and then monthly for a maximum of 1 year. Of the 47 high and 38 low dose patients 20 (43%) and 2 (5%), respectively, achieved a complete response. Additionally, partial responses (cytology results positive with no histological evidence of carcinoma in situ) were noted in 23% of the high dose group. Notably, 6 of 9 patients who had failed prior intravesical bacillus Calmette-Guerin therapy responded to alpha 2b-interferon treatment. Preliminary assessment has shown that among the complete responders 18 of 20 (90%) in the high dose group have maintained responses for at least 6 months after the completion of treatment (10 for more than 12 months). Seven patients in each treatment group have undergone radical cystectomy. All 14 patients had progressive disease except 1 who chose cystectomy although she was still responding to treatment. The median intervals from initial treatment to cystectomy were 18 and 32 weeks in the low and high dose groups, respectively. Local irritation or toxicity did not occur and other adverse effects were rare except for mild to moderate flu-like symptoms (8% in the low dose and 17% in the high dose groups). No patient discontinued therapy due to treatment-related adverse effects. Intravesical alpha-2b-interferon demonstrated a high level of activity in the treatment of carcinoma in situ of the bladder with the 100 million unit dose producing a significantly greater response rate (43% complete response, p less than 0.0001) than the low dose (5% complete response). Safety and tolerance were excellent with no local irritative toxicity. PMID- 2201796 TI - The efficacy of norfloxacin in the treatment of chronic bacterial prostatitis refractory to trimethoprim-sulfamethoxazole and/or carbenicillin. AB - We treated 15 men who had chronic bacterial prostatitis refractory to trimethoprim-sulfamethoxazole and/or carbenicillin with 400 mg. norfloxacin twice daily for 28 days. All pathogens were susceptible to norfloxacin and absent in prostatic fluid cultures obtained during therapy. One patient had negative post therapy prostatic fluid cultures but was lost to followup at 1 month. Of the 14 patients followed for at least 6 months 9 (64%) were cured of the original infection, including 6 who have remained uninfected and have had negative prostatic secretion and urine cultures for at least 2 years (1), 1 year (2) or 6 months (3). In 3 patients urinary tract infections recurred with new pathogens at 6, 560 and 820 days after post-therapy negative prostatic fluid cultures. Bacterial prostatitis with the original pathogen recurred in 5 patients within 2 months of completing therapy. The bacteria remained susceptible to norfloxacin but could not be eradicated with 30 to 90 days of additional norfloxacin therapy. Cures were achieved in 9 of 12 patients with Escherichia coli, none of 2 with Pseudomonas prostatitis and 3 of 5 with prostatic calculi. No patient experienced significant adverse effects. The data suggest that norfloxacin is effective and safe for the treatment of refractory chronic bacterial prostatitis. PMID- 2201797 TI - The use of transrectal ultrasound in the detection and evaluation of local pelvic recurrences after a radical urological pelvic operation. AB - Transrectal ultrasound was performed in 20 patients with suspected local pelvic recurrence after a radical pelvic operation: 9 had undergone radical prostatectomy and 11 had undergone radical cystoprostatectomy. Transrectal sonography verified the presence of recurrence in 19 of 20 patients (95%) and this was confirmed by biopsy of the visualized lesions. Analysis of the sonographic echo patterns encountered revealed that in 14 of 19 recurrent neoplasms (71.5%) the echogenic pattern was hypoechoic. In the remaining 6 patients (31.5%) the echo pattern was isoechoic. No hyperechoic lesions were noted. Based upon our findings and because of the low costs compared to other diagnostic modalities transrectal ultrasound represents an ideal technique to compliment the digital rectal examination in evaluation of patients suspected of harboring a local pelvic recurrence after a radical pelvic operation. PMID- 2201798 TI - Bacterial epididymitis in the rat: a model for assessing the impact of acute inflammation on epididymal antibiotic penetration. AB - A rat model of bacterial epididymitis was developed and characterized for use in assessing the impact of acute epididymal inflammation on antibiotic penetration into the epididymis. A 0.2 ml. intratesticular injection of a 0.5 McFarland standard suspension of E. coli resulted in histologically confirmed acute epididymitis in all animals studied. Inflammatory changes were detectable as early as 24 hours following inoculation and were progressive to the last assessment point at 11 days. Early testicular infarction was observed in association with epididymal inflammation. Serial transcrotal ultrasounds of infected animals showed progressive increase in epididymal size and a late decrease in testicular size. Serum and epididymal drug concentrations were assayed following a single dose of the antibiotic amdinocillin. Fifteen minutes following the peak serum level, the drug concentration in infected epididymis was 2.3-fold higher than the contralateral, non-infected epididymis. These data suggest that acute inflammation enhances antibiotic penetration into the infected epididymis. The model described provides a rapid, reproducible method to study epididymal drug delivery in normal and diseased states. PMID- 2201799 TI - Mechanisms of human bladder tumor invasion: role of protease cathepsin B. AB - To study the biochemical mechanisms of bladder tumor invasion, we analyzed specimens of invasive transitional cell carcinoma cell line EJ and non-invasive transitional cell carcinoma cell line RT4 which had been implanted into the bladders of nude mice. Using immunoprobes specific to basement membrane laminin, we observed that superficial but not invasive tumors were surrounded by intact laminin. With immunoprobes specific to cathepsin B, a cysteine proteinase which has the ability to degrade laminin, we demonstrated that cathepsin B is localized in discrete cytoplasmic granules in the non-invasive tumors, and in a more diffuse cytoplasmic pattern in the invasive tumors. Subcellular fractionation followed by immunoblot analysis and enzymatic analysis confirmed that the invasive EJ cells had active cathepsin B localized to its plasma membrane, while non-invasive RT4 cells had cathepsin B confined to lysosomes. Furthermore, immunoblot analysis revealed that invasive EJ cells had the mature form of cathepsin B with a molecular weight of 25 kD, while non-invasive RT4 cells had predominantly precursor forms with molecular weights between 30 and 35 kD. In vitro degradation assays with plasma membrane fractions isolated from invasive EJ cells and non-invasive RT4 cells demonstrated that the plasma membrane of EJ cells but not that of the RT4 cells had the ability to degrade purified laminin, and that the degradative products were similar to those obtained with purified cathepsin B. We conclude that invasive tumor cells have enhanced cathepsin B in their plasma membranes which may be used to degrade basement membrane components such as laminin and thereby facilitate tumor invasion. PMID- 2201801 TI - Medical revolution in Minnesota: a history of the University of Minnesota Medical School. PMID- 2201800 TI - Strongyloidiasis in cotton rats (Sigmodon hispidus) from central Oklahoma. AB - Thirty-one of 40 cotton rats (Sigmodon hispidus) collected from central Oklahoma were infected with Strongyloides sp. (78% prevalence). Larvae of Strongyloides sp. (rhabditiform or filariform) were not demonstrable in intestinal contents and scrapings. Female nematodes recovered from intestinal contents and scrapings had morphological similarities with Strongyloides sigmodontis. Cotton rats infected with Strongyloides sp. were indistinguishable clinically from non-infected hosts. Infected animals had no significant gross lesions, but the presence of Strongyloides sp. in the intestinal mucosa was associated with villus atrophy and mild to moderate infiltration of the lamina propria by lymphocytes, plasma cells and occasional eosinophils. Other organs or tissues examined were free from lesions induced by Strongyloides sp. PMID- 2201802 TI - The association of payer with utilization of cardiac procedures in Massachusetts. AB - To investigate the importance of the payer in the utilization of in-hospital cardiac procedures, we examined the care of 37,994 patients with Medicaid, private insurance, or no insurance who were admitted to Massachusetts hospitals in 1985 with circulatory disorders or chest pain. Using logistic regression to control for demographic, clinical, and hospital factors, we found that the odds that privately insured patients received angiography were 80% higher than uninsured patients; the odds were 40% higher for bypass grafting and 28% higher for angioplasty. Medicaid patients experienced odds similar to those of uninsured patients for receiving angiography and bypass, but had 48% lower odds of receiving angioplasty. In addition, the odds for Medicaid patients were lower than for privately insured patients for all three cardiac procedures. These findings suggest that insurance status is associated with the utilization of cardiac procedures. Future studies should determine the implications these findings have for appropriateness and outcome and whether interventions might improve care. PMID- 2201804 TI - [Convulsive seizures and heterotopic gray matter; report of two cases]. AB - We reported CT and MRI findings of heterotopic gray matter in two patients with intractable convulsive seizures. CT demonstrated space-occupying but non expansive lesions isodense with the cortical gray matter adjacent to the body of the lateral ventricle. These lesions were not enhanced with contrast infusion. MRI was performed in one case in which the lesion was isointense with the cortical gray matter. PMID- 2201805 TI - [A case of leiomyoblastoma of the duodenum]. PMID- 2201803 TI - The 'Medicaidization' of AIDS. Trends in the financing of HIV-related medical care. AB - Among patients with the acquired immunodeficiency syndrome (AIDS) who were hospitalized in New York City, San Francisco, Calif, and Los Angeles, Calif, from 1983 through 1988, we observed a marked shift in the payer distribution toward Medicaid and away from private insurance. This trend, which we refer to as the "Medicaidization" of AIDS, occurred among whites as well as blacks and Hispanics and increased the burden on public hospitals and emergency rooms. "Medicaidization" jeopardizes access to office-based primary care because of very low reimbursement rates that are paid to physicians by Medicaid relative to private insurance. Policies designed to prevent the loss of employment-based private insurance would slow or reverse the trend to public financing. Increasing Medicaid reimbursement will improve access to care. PMID- 2201806 TI - [A case of leiomyosarcoma of the gallbladder]. PMID- 2201807 TI - [A case of Buerger's disease causing fatal large intestinal necrosis complicated with chronic pancreatitis]. PMID- 2201808 TI - [A case of malignant peritoneal mesothelioma diagnosed by ascitic fluid aspiration with a 28-year history of asbestos exposure]. PMID- 2201809 TI - A modified version of Herrera's method for creating a pancreatic fistula in dogs. AB - Various cannulae have been devised to serve in experiments for collecting pancreatic juice. In this study we created a pancreatic fistula in dogs through a modification of Herrera's method. Since it is advisable to make as small a duodenal pouch as possible to collect almost all the secreted pancreatic juice, both ends of the pouch were closed by an inverted continuous all-layer suture. The lateral flange of the cannula was then introduced into the pouch to sample the pancreatic juice. Duodenoduodenostomy was performed to restore continuity of the alimentary tract, and the other end was inserted into the duodenum 3 cm distal to the anastomosis on the anal side. The exocrine pancreatic secretion of these dogs responded well to food ingestion, with a peak level of 14.5 +/- 5.4 ml/15 min appearing after 30 to 45 min in a postprandial state. Moreover, the animals were able to survive and be utilized for experiments for a period of 3 to 5 months. This experimental model is therefore considered to be of great value for the investigation of exocrine pancreatic secretion. PMID- 2201810 TI - A case of pheochromocytoma with severe paralytic ileus. AB - We report herein a rare case of a 26 year old woman with pheochromocytoma complicated by paralytic ileus. She presented with remarkable abdominal distension and respiratory difficulty but was effectively treated by surgical removal of the tumor with preoperative and operative management using alpha and beta adrenergic blocking agents. An excessive and persistent catecholamine production from large tumors or massive metastases characterizes this rare complication, and a review of the English and Japanese literature is given following this report. PMID- 2201811 TI - Lipoma of the esophagus--report of a case and review of the literature. AB - We report herein, a rare case of esophageal lipoma and review the Japanese literature on this subject. Lipoma of the alimentary tract is relatively uncommon but that of the esophagus is extremely rare with only 17 cases having been reported in Japan. The majority of these cases occurred in the cervical esophagus with the most serious symptom being regurgitation of the pedunculated tumor which lead to asphyxia and death in one case. Only 2 cases occurred in the thoracic esophagus and these tumors were small in size and resected endoscopically. This is the first reported case of an esophageal lipoma being located in the thoracic esophagus which was resected through a thorocotomy. The clinical features of esophageal lipoma are also described herein. PMID- 2201812 TI - Right ventricular myocardial infarction and late cardiac tamponade due to right coronary artery aneurysm--a case report. AB - Coronary artery aneurysm is a relatively rare disease, which may cause angina, myocardial infarction, or sudden unexpected death due to thrombosis, embolization or rupture. This report describes a case of a 46 year old male who suffered an inferior myocardial infarction with right ventricular involvement, third degree atrioventricular block, cardiogenic shock and late cardiac tamponade, all caused by a right coronary artery aneurysm. He was successfully treated with emergency coronary artery bypass grafting. A review of the literature is also given to emphasize the importance of prompt recognition and correct management of the coronary artery aneurysm. PMID- 2201813 TI - A rectal carcinoid tumor of less than 1 cm in diameter with lymph node metastasis: a case report and a review of the literature. AB - We report herein, a patient with a rectal carcinoid tumor of less than 1 cm in diameter with lymph node metastasis, and discuss a surgical policy for these lesions with reference to other such cases reported in the literature. A 40 year old female was admitted with a rectal mass and colonoscopy revealed a subpedunculated lesion, 1 cm in diameter, with a depression in its tip. A diagnosis of carcinoid was made by biopsy and transsacral excision performed. The excised specimen revealed a subpedunculated lesion measuring 7 X 6 X 6 mm with a central depression. The tumor was histologically confined to the submucosa but lymphatic invasion with pararectal lymph node involvement was observed. A radical proctectomy was thus performed. The incidence of metastasis from rectal carcinoids with a diameter of 1 cm or less is very low ranging from 1.5 to 3.4 per cent, and it therefore seems that most lesions of 1 cm or less in diameter can be treated by local excision alone. Thus, although it is recommended that local excision be performed first to determine the extent of spread, lymphatic vessel invasion and lymph node metastasis, radical surgery is indicated if lymphatic invasion or nodal involvement is present, even when muscle invasion is absent. PMID- 2201814 TI - Alveolar soft part sarcoma: a case report with immunohistochemical study. AB - We report herein, a rare case of a 28 year old Japanese man with alveolar soft part sarcoma. The patient noticed a rapidly growing mass in the inner aspect of his left thigh and a smooth-surfaced, hard nodule revealing bruit on auscultation was found on physical examination. An angiogram showed dense neovascularity from the left profunda femoris artery. Histopathologically, the tumor was composed of nests of tumor cells with hyperchromatic nuclei and vesicular cytoplasm arranged in an alveolar fashion and a histopathologic diagnosis of alveolar soft part sarcoma was made. Immunohistochemically, the tumor cells had desmin and vimentin immunoreactants in the cytoplasm, suggesting muscle origin. PMID- 2201816 TI - The Kansas Medical Society membership directory 1990. PMID- 2201815 TI - Mid-mediastinal parathyroid lesions: preoperative localization and surgical approach in two cases. AB - Although hyperfunctioning mediastinal parathyroid lesions that require median sternotomy or thoracotomy for removal are occasionally present, the majority are located in the anterior mediastinum closely associated with the thymus. Only eight cases of ectopic hyperfunctioning parathyroid tumors in the middle mediastinum have been reported. We experienced two cases of either persistent or recurrent hyperparathyroidism in which abnormal parathyroid tissue was located in the aorticopulmonary window. One of the patients had a parathyroid adenoma and the other had metastatic lesions of parathyroid carcinoma. In both cases, thallium scanning proved useful in identifying the lesions while computed tomography scan was effective for mediastinal three-dimensional localization. In one case, single photon emission computed tomography imaging with thallium proved beneficial for both identification and localization of the middle mediastinal lesion. The surgical approach used in both cases was different. In one case, left thoracotomy was performed, after which the ligamentum arteriosum was divided, and an adenoma anterior to the left main bronchus and posterior to the left pulmonary artery removed. In the other case, two metastatic tumors of parathyroid carcinoma anterior to the right main bronchus and posterior to the right pulmonary artery were resected through a median sternotomy and opening of the pericardium. PMID- 2201817 TI - Stability of the sociodemographic variance of the Type A behavior pattern in Finnish adolescents and young adults. AB - Stability of the sociodemographic variance of the Type A behavior pattern found in a previous study was studied 3 years later in the same subjects, 1,333 adolescents and young adults. The Type A behavior questionnaire for the Finnish Multicenter Study and the Hunter-Wolf A-B Rating Scale were used to measure Type A behavior. The previous finding, that the results are highly dependent on the method used, was confirmed, and the stability of the findings assessed by the same method was high. The results confirm the previous suggestion that Type A behavior is not indisputably a pattern characterizing male, urban, and middle-to upper economic and educational subgroups; the interactions among different sociodemographic variables are more complex. PMID- 2201818 TI - Pathophysiology of cytokines. AB - Beside their therapeutic effects, cytokines are involved in pathologies such as IL-6 in myeloma tumor growth and bone resorption, BCGF in the proliferation of hairy cell leukemic cells, IL-2 in the capillary leak syndrome. For biotherapy to develop, it is necessary to understand both the beneficial and the deletorious effects of cytokines. PMID- 2201819 TI - Growth of normal and malignant bone marrow cells. AB - Results of five different methods (heme breakdown, mitotic indices, total marrow cellularity and different methods of labelling indices) to determine bone marrow cell growth are reviewed. Normal immature erythroblasts and myeloblasts have generation times of about 5-10 h. Erythroblasts in neoplastic conditions (the myelodysplastic syndrome and polycythemia vera) have generation times which are significantly prolonged, by 12-75 per cent, but this may not be true for myeloblasts, since total labelling indices are increased (from normal 3.9 to 11.2 per cent) in the myelodysplastic syndrome. In contrast, generation times in aplastic anemia are significantly shortened, by about 70-80 per cent. Normal mature erythroblasts and promyelocytes have generation times of about 24 h, and the malignant prolongation may be even greater. PMID- 2201820 TI - Erythropoietin. AB - The remarkable capacity of the bone marrow to compensate for blood loss and for reduced atmospheric oxygen tension has been found to be mediated by a renal hormone, named erythropoietin. It is produced by peritubular interstitial cells in response to renal hypoxia, but molecular engineering has permitted large scale production of an identical recombinant erythropoietin in vitro. When used as a replacement hormone in patients with impaired endogenous production it has been found to be capable of improving or eliminating the anemia of chronic kidney disease and the anemia of prematurity. In the future it may also be used as a pharmacologic agent and possibly be able to control the anemia of patients with bone marrow failure and make them transfusion-independent. PMID- 2201821 TI - Interleukin 2 receptors. AB - Interleukin 2 receptors (IL-2-R) are composed of (at least) two chains: the alpha chain (or p55 or Tac) and the beta chain (or p70 or p75). The association of both chains constitutes high affinity IL2-R complexes (Kd congruent to 10-100 pM), whereas the alpha-chain or the beta chain alone bind IL-2 with low (Kd congruent to 5-50 nM) and intermediate (Kd congruent to 1 nM) affinities, respectively. The beta chain (but not the alpha chain) mediates IL-2 internalization and signal transduction (proliferation or differentiation) to the cell, thus only high and intermediate affinity IL-2-R are functional. High affinity IL-2-R are expressed on activated normal and leukemic T and B lymphoid cells. Low affinity IL-2-R (Tac alone) are seen on stimulated T cells, B cells, and monocytes, as well as on various leukemic cells. The p70 chain alone is constitutively expressed by subsets of normal resting T and B cells, LGL and NK cells and we have recently demonstrated its presence on leukemic cells from various hemopoietic lineages. The finding of IL-2-R on non-lymphoid cells may disclose new functions for IL-2. PMID- 2201822 TI - Tumor associated myelopoiesis inhibiting factors. AB - The best characterized hemopoietic growth inhibitors in myeloid leukemias are leukemia associated inhibitor (LAI) and leukemia inhibitory activity (LIA). Both are normal cell products overproduced in leukemia. LIA is identical to acid isoferritin and LAI is not identical to LIA. They act in different ways to inhibit normal stem cell growth. The over-production of these putative normal regulators may explain the suppression of normal hemopoiesis typical of myeloid leukemias. Modulation of the production and the action of LAI and LIA therefore have potential therapeutic value in leukemia. PMID- 2201823 TI - Differentiating agents in the treatment of leukemia. AB - The aim of differentiation therapy is to induce a maturation of the leukemic clone. Various approaches have been used: suppression of proliferation by low dose Ara-C in acute myeloid leukemia (AML); enhancement of differentiation by retinoic acid derivatives in acute promyelocytic leukemia (APL) or by differentiation-inducing factors; modulation of cell metabolism by breaking an autocrine loop in hairy cell leukemia (HCL). In all cases the treatment is given continuously at small doses over a long period of time. The very significant clinical results which have been obtained mainly in APL with all-trans retinoic acid and in HCL with alpha-interferon are briefly discussed. PMID- 2201824 TI - Differentiating agents in the treatment of leukemia and myelodysplastic syndromes. AB - Differentiation therapies try to change the malignant cell in order to acquire a more mature or normal phenotype. Various ways were tested in leukemia: suppression the proliferative pressure by low dose Ara-C, enhancement of the differentiation by retinoic acid derivatives or by differentiation factors, and modulation of the cell metabolism interrupting an autocrine loop (a growth factor and its receptor). The treatment is given continuously at small doses, during a long period of time. In all these cases it seems necessary to tailor the differentiation therapy to each category of leukemia. PMID- 2201825 TI - Cure of acute myelocytic leukemia in adults: a reality. AB - Adult acute myelocytic leukemia (AML) is a curable disease in responsive patients with aggressive treatment in remission. Over the past decade at the Johns Hopkins Oncology Center, AML has been treated with either allogeneic bone marrow transplantation or with intensive timed sequential treatment using high dose cytarabine in remission. With either treatment modality comparable cure rates were obtained. The role, if any, of randomized trials to adequately determine the preferred treatment for appropriate patients has yet to be defined. PMID- 2201826 TI - IL-3 inhibits the binding of GM-CSF to AML blasts, but the two cytokines act synergistically in supporting blast proliferation. AB - Equilibrium binding of 125I-labeled recombinant granulocyte macrophage colony stimulating factor (GM-CSF) to the blast cells of acute myeloblastic leukemia (AML) revealed the presence of two classes of binding components of high and low affinity, with dissociation constants (Kd) in the range of 5-10 pM and 1-10 nM, respectively. Specificity studies revealed that interleukin-3 (IL-3) could partially inhibit the binding of GM-CSF to AML blasts and to the cells of the leukemic lines M07-E, KG-1, and HL-60. The inhibition of GM-CSF binding by IL-3 was directly dependent on the presence of IL-3 receptors. Analysis of competition curves indicated that the Kd and the number of binding sites per cell of unlabeled and iodinated GM-CSF were identical. In contrast, the inhibition of GM CSF binding by IL-3 was mediated by IL-3 occupancy of a high affinity receptor only, with the same number of sites as the high affinity GM-CSF receptor but a slightly higher Kd. Despite this competitive binding, IL-3 augmented AML blast proliferation in the presence of GM-CSF, indicating that the two growth factors have converging pathways in supporting blast proliferation. In striking contrast to AML blasts, GM-CSF binding to neutrophils was compatible with the presence of only one class of binding site of intermediate affinity (Kd approximately 100-160 pM). Furthermore, IL-3 does not compete for the binding of GM-CSF to neutrophils. PMID- 2201827 TI - The effect of cytokines, including IL-1, IL-4, and IL-6, in hairy cell proliferation/differentiation. AB - IL-1, IL-4, and IL-6 had no effect on hairy cell (HC) proliferation in vitro. Anti-mu and low molecular weight B cell growth factor (LBCGF) and tumor necrosis factor alpha (TNF-alpha) stimulated the proliferation of a minor subpopulation of HCs detected by double immunocytochemical staining. None of these cytokines had any effect on HC differentiation as measured by immunoglobulin secretion. It is concluded that none of the above growth factors are central to HC proliferation in-vivo. Since alpha-interferon IFN-alpha, but not IFN-gamma, consistently inhibited any proliferation observed, it seems likely that this monokine has a direct antiproliferative effect in vivo. PMID- 2201828 TI - Monosomy-7 in childhood hemopoietic disorders. AB - Acquired pure monosomy-7 is associated with various myeloproliferative disorders (MPD), myelodysplasias (MDS), and acute myeloblastic leukemias (AML) in children and a poor prognosis. A series of 14 malignant blood disorders with pure monosomy 7 in children (eight MPD, two refractory anemia with excess of blasts, (RAEB), and four AML) is reported and compared with cases in the literature. The median age is significantly different in the patients with MPD and those with MDS or AML: 23, 80.5, and 112 months, respectively. The outcomes of MPD and RAEB are characterized by a high risk of rapid blastic transformation and resistance to polychemotherapy. Bone marrow transplantation (BMT) seems to be the best treatment, and one survival of two years in complete remission after autologous BMT in a child with AML is reported. Several myeloid cell lineages are involved in the proliferation, which partly explains the difficulties of cytologic classification and suggests that a pluripotent stem-cell is at the origin of the disease. PMID- 2201829 TI - Translocation t(3;22)(q23;q11) in three patients with diffuse large B cell lymphoma. AB - In our series of 134 patients with a diagnosis of non-Hodgkin's lymphoma (NHL) and clonal chromosomal abnormalities, three were found to show an identical t(3;22)(q28;q11) translocation. All were old patients with isolated lymphadenomegaly and diffuse large noncleaved cell lymphoma. All expressed a B cell immunophenotype, and all entered a complete remission when treated with aggressive chemotherapy. This translocation could, therefore, delineate a particular subtype of diffuse large cell NHL. PMID- 2201830 TI - Blast crisis accompanied with occurrence of the point-mutational activation of N ras proto-oncogene and the chromosomal abnormality inv(3q) in chronic myelogenous leukemia presenting thrombocytosis. PMID- 2201831 TI - Expression of a human homing receptor (CD44) in lymphoid malignancies and related stages of lymphoid development. AB - Lymphocyte adhesion to high endothelial venules, a central step during extravasation into lymphoid tissues, involves an 85 to 95-kD class of lymphocyte surface glycoproteins, which fall in the cluster of CD44 antigens. In this paper we describe the expression of this homing receptor glycoprotein during lymphoid development. CD44 expression was examined on a large panel of non-Hodgkin's lymphomas (n = 234) and lymphoid leukemias (n = 44). These tumors, which are the malignant counterparts of normal lymphoid cells "frozen" at a certain stage of maturation/activation, are thought to represent a complete spectrum of lymphoid development from stem cell to mature, activated T and B lymphocyte. It was found that CD44 exhibits a trimodal distribution on developing lymphocytes of both the T and B lineage: the CD44 antigen is expressed at relatively high levels during early stages of lymphoid differentiation, i.e., on prothymocytes and immature precursor B cells (null acute lymphoblastic leukemia (ALL) and common ALL). Subsequently, at the stage of the immature/common thymocyte, the pre-B cell and early B cell (pre-B-ALL and B-ALL), the CD44 antigen is temporarily lost from the cell surface to be reacquired during further T and B cell maturation. At the activated (germinal center) B cell stage. CD44 is heterogeneously expressed. This distribution pattern of the CD44 molecule closely matches the recirculatory versus sessile nature of lymphoid cells at consecutive phases of their development, and thus apparently reflects its homing receptor function. In addition, the relatively high expression of the CD44 antigen in the earliest phases of T and B cell development suggests that the molecule may also be involved in the migration of bone marrow derived lymphoid precursors to their site of maturation. PMID- 2201832 TI - Expression of bcr-abl fusion transcripts following bone marrow transplantation for Philadelphia chromosome-positive leukemia. AB - A modified polymerase chain reaction (PCR) procedure was used to study the expression of bcr-abl fusion transcripts following allogeneic bone marrow transplantation (BMT) for Philadelphia chromosome (Ph1) positive acute and chronic leukemias. The technique was applied to RNA preparations of peripheral blood and bone marrow cells from 10 patients with chronic myelogenous leukemia (CML) and one patient with acute lymphoblastic leukemia (ALL), all of whom had undergone allogenic BMT and were in clinical and cytogenetic remission. Pre-BMT samples available for eight of 11 patients contained detectable bcr-abl fusion products serving as a baseline for comparison to post-BMT studies. Six patients showed no PCR-detectable bcr-abl transcripts in each of several serial analyses post-BMT (1-36 months post-BMT). The remaining five patients demonstrated various patterns of bcr-abl transcript expression after transplantation. In three patients, bcr-abl transcripts persisted for up to 3 months post-BMT but subsequently were undetectable. Molecular relapse was observed 3 and 6 months post-BMT in the remaining two patients whose earlier post-BMT samples showed no bcr-abl fusion transcripts. No bcr-abl transcripts were detected in subsequent samples from both of these patients 6 months and 1 year post-BMT, respectively. These data confirm that Ph1 carrying cells expressing the bcr-abl fusion mRNA may persist or recur for several months following BMT in the absence of clinical and cytogenetic relapse. The significance of these observations is discussed with respect to results reported recently by others using similar techniques. PMID- 2201833 TI - Effects of rhGM-CSF on intracellular ara-C pharmacology in vitro in acute myelocytic leukemia: comparability with drug-induced humoral stimulatory activity. AB - Human acute myelocytic leukemia (AML) marrow cells respond to stimulation with increased proliferation and enhanced intracellular metabolism of the cytotoxic antimetabolite 1-B-D arabinofuranosylcytosine (ara-C). Our previous studies have focused on the drug-induced humoral stimulatory activity (HSA) present in serum following initial cytoreduction which augments in vitro growth and biochemical pharmacology. The activity of HSA likely relates to the presence of multiple stimulators. The effect of 18-hr culture in purified recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) (1 ng/ml) on in vitro AML marrow cell [3H]dThd incorporation into DNA, intracellular ara-C activation to the triphosphate form (ara-CTP), and subsequent ara-CTP retention were determined in leukemic cells of 11 patients and compared with cells similarly cultured in HSA-containing sera. The stimulatory effects of rhGM-CSF and HSA on both growth and pharmacologic parameters were comparable for each AML population, with maximal response to both regulators detected for FAB M2. These data demonstrate that GM-CSF acts similarly to HSA as an active stimulator of leukemic cell proliferation and net intracellular ara-C metabolism in vitro, and support clinical trials designed to examine the role of rhGM-CSF in enhancing ara-C cytotoxicity by increasing the growth fraction of drug-responsive target cells in vivo. PMID- 2201834 TI - Hemopoietin-1 activity of interleukin-1 (IL-1) on acute myeloid leukemia colony forming cells (AML-CFU) in vitro: IL-1 induces production of tumor necrosis factor-alpha which synergizes with IL-3 or granulocyte-macrophage colony stimulating factor. AB - Interleukin-1 (IL-1) has hemopoietin-1 (H-1) activity, i.e., it synergizes with macrophage-colony stimulating factor (M-CSF), granulocyte-macrophage-CSF (GM-CSF) and interleukin-3 (IL-3) in stimulating in vitro colony formation of hematopoietic progenitor cells. In this study the synergistic activity of IL-1 was investigated on IL-3 and GM-CSF induced growth of acute myeloid leukemia colony forming cells (AML-CFU) in vitro. Among 12 cases of human AML, IL-1 significantly elevated IL-3 stimulated colony numbers in eight instances and enhanced GM-CSF induced colony growth in five cases. As IL-1 is an inducer of cytokine production and since tumor necrosis factor (TNF) elevates IL-3 or GM-CSF induced proliferation of AML-CFU, we examined whether IL-1 enhanced AML-CFU growth via the induction of TNF production. Neutralizing anti-TNF-alpha antibodies significantly decreased IL-1/IL-3 or IL-1/GM-CSF stimulated colony numbers in six of seven cases studied, whereas anti-TNF-beta had no effect, indicating that endogenously produced TNF-alpha costimulated the growth of AML CFU. Furthermore, AML blast cells stimulated by IL-1 released increased amounts of TNF-alpha (between 25 and 533 pg/ml; median 255 pg/ml) into the culture medium (TNF-alpha specific radioimmunoassay) as compared with noninduced AML cells (less than 1 to 149 pg TNF-alpha/ml; median 31 pg/ml). Thus, the effect of IL-1 on AML CFU proliferation is not the result of direct activation of AML progenitors, but IL-1 stimulates the release of TNF-alpha by AML cells and endogenous TNF subsequently synergizes with IL-3 or GM-CSF. PMID- 2201835 TI - Splenic hematopoiesis following GM-CSF therapy in a patient with hairy cell leukemia. PMID- 2201836 TI - Dr. William J. Mayo's 1895 commencement address. PMID- 2201837 TI - Obstructive sleep apnea syndrome. AB - Obstructive sleep apnea syndrome is the most common cause of hypersomnolence in patients referred to sleep disorders centers. This type of sleep apnea is characterized by loud snoring, nocturnal oxyhemoglobin desaturation, and disrupted sleep that leads to daytime hypersomnolence. The anatomic configuration of the pharynx and the physiologic responses to occlusion of the upper airway play a major role in the pathogenesis of this disorder. Polysomnography can accurately identify obstructive sleep apnea, and the multiple sleep latency test allows an objective measurement of daytime alertness. Weight loss and training the patient to sleep in a lateral position are frequently used to alleviate mild cases. Nasally applied continuous positive airway pressure is an extremely effective modality for treating moderate and severe obstructive sleep apnea. Surgical correction of obvious anatomic defects has a role in diminishing obstructive sleep apnea, but the exact role of surgical intervention in patients without obvious anatomic defects remains unknown. The choice of therapy should be tailored to the individual patient with sleep apnea, and careful follow-up is essential to ensure a positive response to therapy. PMID- 2201838 TI - Nasal influences on snoring and obstructive sleep apnea. AB - Although the relationship between nasal obstruction and sleep disturbance is variable, either partial or total obstruction of the nasal passages can cause snoring, obstructive sleep apnea, and the sequelae of alveolar hypoventilation. In addition, nasal obstruction can cause sleep fragmentation, sleep deprivation, and the known sequelae of disturbed sleep architecture, including associated daytime tiredness and alterations in normal behavior patterns. Nasal obstruction may produce greater physiologic effects during sleep than during the awake state. A complete examination of the upper respiratory tract should be done in all patients with obstructive sleep apnea and snoring. The degree of nasal obstruction is not directly correlated with the severity of symptoms and findings. PMID- 2201839 TI - Medical symbols: the caduceus. PMID- 2201840 TI - [Importance and need of bibliographic access in medical research and practice]. PMID- 2201842 TI - [Systemic sclerosis (sclerodermia)]. PMID- 2201841 TI - [Morphologic studies in generalized persistent lymphadenopathy syndrome]. PMID- 2201843 TI - [Autoimmune hemolytic anemia and CREST syndrome]. AB - There are few studies addressing the frequency and etiology of anemia in progressive systemic sclerosis. Anemia is present in about 25% of these patients. Among the implicated causes are ferropenia, generally associated with gastrointestinal hemorrhage, and renal failure. In a considerable number of patients, the specific etiology of anemia remained unknown. We report a 59-year old female with autoimmune hemolytic anemia and incomplete CREST syndrome. We emphasize the rarity of autoimmune hemolysis as a cause of anemia in systemic sclerosis, and we discuss its significance as indirectly supporting the possible autoimmune pathogenesis of that condition. PMID- 2201844 TI - [Effects of radiotherapy on the heart]. PMID- 2201845 TI - Approach to the adolescent in the clinical setting. AB - Life is a series of adolescent experiences, whether these be personal, professional, familial, or community oriented. The biogenesis of puberty, although striking, reveals only a small part of the change that occurs. The accompanying psychosocial changes (adolescence) dynamically interact to create an indelible mark on maturation. A healthy adolescence is one that reflects flexibility within established boundaries, adaptation to change, and growth, all manifested through an increased sense of well-being. Youth becomes not a time of life, but a frame of mind. Physicians who enjoy working with adolescents are those who can tolerate and enjoy growth and change. The venture requires awareness, courage, and sensitivity, but the rewards are commensurate with the commitment. PMID- 2201846 TI - Treating adolescents. Legal and ethical considerations. AB - Treating adolescents in the health care system raises significant legal and ethical issues related to consent for treatment, confidentiality of communications and records, and payment for care. The law provides many opportunities for adolescents to consent to their own care and offers significant protections of confidentiality. Publicly funded programs provide access to free care for some adolescents, but financial considerations continue to limit access for many poor and low-income adolescents. In addition to legal concerns, serious ethical dilemmas arise, particularly with respect to treatment of special populations of adolescents. Resolution of the legal and ethical questions requires cooperation of professionals from many disciplines. PMID- 2201847 TI - Life beyond pediatrics. Transition of chronically ill adolescents from pediatric to adult health care systems. AB - Transition from pediatric to adult health care is fraught with difficulties. On the one hand, the adult care system is not properly prepared to receive patients who are survivors of the so-called childhood disorders. On the other hand, patients and families have difficulty leaving the protective environment created by pediatric caregivers, who in turn may have mixed feelings about letting the patients go. Normalization of development and social adaptation for chronically ill adolescents, however, should include a change in the environment in which health care is received. This article examines some of the issues surrounding transition and transfer from pediatric to adult health care systems and propose some avenues toward implementation of such programs. PMID- 2201848 TI - Psychosomatic symptoms in adolescence. AB - This article provides the physician with an efficient and comprehensive method for the evaluation and management of adolescent psychosomatic symptoms in the medical care setting. The physician should make a firm statement of the nonorganic nature of the psychosomatic symptom, identify significant stressors, and provide strong recommendations for immediate action. Appropriate referrals should be arranged, and a follow-up visit to assess progress several weeks after the evaluation should be scheduled. PMID- 2201849 TI - Adolescent wellness. Facilitating compliance in social morbidities. AB - The establishment of a well adolescent schedule needs to be developed similar to the scheduled clinical visits in pediatric care. However, providing adolescent wellness visits without appropriate financial reimbursement for time expended and without increased provider training may make "well" adolescent visits an unrealistic expectation. However, two major trends will significantly impact on the future of adolescent health care. These include a sharp increase in numbers of adolescents beginning in 1990 and the poverty within the adolescent population. These data suggest that obstacles, whether personal, financial, or educational, need to be addressed quickly in order to resolve these problems because of increasing numbers of adolescents and related morbidities through the year 2000. The increasing trend of juvenile poverty in this population has been significantly associated with a number of the new morbidities such as substance abuse, STD, pregnancy, and the latest morbidity, AIDS. Without a wellness schedule, it is likely that adolescents will continue to represent an underserved population; as a consequence, mortalities and morbidities will increase through the year 2000. The issue of adherence to prescribed medical regimens in the adolescent population is an interesting, complex, and especially challenging one when faced with the social morbidities. Although preliminary work in this area has progressed in the last 15 years, greater attention must be paid to the needs of adolescents in order to determine effective strategies that can minimize the effects of the current morbidities. It is important for the primary care physician not to become overwhelmed with the scope of problems that adolescents have or become discouraged because anticipatory guidance seems ineffective. Repeated dosages of anticipatory guidance should not be viewed as limitations or failures but rather as necessary and standard care. One should consider such interventions as similar to immunizations, in which certain vaccines result in life-long immunity. One would not eliminate the tetanus vaccine because the patient must receive periodic boosters. Similarly, as health care professionals, we should not consider interventions designed to preclude behavior or mental health problems as failures if periodic and developmentally appropriate relevant "boosters" are necessary. Anticipatory guidance is an extremely effective tool that every primary care physician has at his or her disposal to assist in the diagnosis of problematic behavior in adolescents and to preclude problems. Future research needs to focus on documenting strategies that can be utilized by physicians on a daily basis without excessive time or financial constraints.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2201851 TI - Fundamental issues in the care of homosexual youth. AB - The development of a homosexual identity spans the entire life cycle, but adolescence is a critical period in the lives of gay and lesbian persons. Various pre- and postnatal biologic and environmental factors are thought to determine sexual orientation early in life. An emerging homosexual identity may be reflected in youths' sexual attractions, fantasies, and cultural affiliations, as well as their behaviors. The adolescent experiences of homosexual persons profoundly affect health outcomes. The goals of care are to promote normal adolescent development, social and emotional well-being, and physical health. Comprehensive and coordinated educational, mental health, social, and medical services are recommended. PMID- 2201850 TI - HIV infection and AIDS during adolescence. AB - It is clear from the evidence that a growing number of adolescents are acquiring HIV infection and developing AIDS. The impact this epidemic will have on all teenagers is overwhelming. Given the high prevalence of risk-related sexual behaviors, many adolescents are likely to become HIV infected, thus requiring extensive medical and psychosocial services. Other adolescents will lose a parent, relative, or friend to AIDS, and these adolescents will similarly require special services and psychological counseling. Thus, there is an immediate need for the development of methods for (1) providing all adolescents with age appropriate and culturally relevant interventions for prevention and risk reduction, (2) identifying high-risk adolescents and triaging them to different levels of care and risk reduction counseling, and (3) providing ongoing medical and psychosocial treatments. Accessing adolescents at risk for HIV infection will require networking between the health care system and youth-serving and community based agencies, particularly agencies servicing high-risk adolescents. We must begin addressing these needs now, in order to prevent further infection and to provide appropriate care for those adolescents who are or will become infected with HIV. PMID- 2201852 TI - Menstrual problems in adolescents. AB - Menarche is a significant event in the course of puberty. Although the age of menarche varies among adolescents, it occurs in most adolescents at an SMR of 4. With the onset of ovulatory cycles, local prostaglandins are released, often causing dysmenorrhea. This usually responds to PSIs. Abnormal uterine bleeding usually is the result of anovulatory cycles. However, complications of pregnancy, systemic illnesses, and local pathology must be considered. Significant bleeding usually responds to hormonal therapy. Amenorrhea may result from abnormalities affecting the hypothalamus, pituitary, or ovaries. The evaluation should be done in a logical, orderly fashion. In addition, pregnancy must always be considered first in the differential diagnosis. PMID- 2201853 TI - Contraception in the adolescent. Preparation for the 1990s. AB - An overview of current and future contraceptive methods available to the adolescent is presented. Emphasis is given to oral contraceptives, including low dose monophasics and triphasics. Current research confirms the efficacy and safety or oral contraceptives for teenagers. Other methods are reviewed, such as the mini-pill, barrier contraceptives (including the cervical cap and female condom), injectable contraceptives, hormonal contraceptive implants, the vaginal ring, postcoital contraception, periodic abstinence, gossypol, and others. Though abstinence is the best contraceptive method for adolescents, contraceptive technology of the 1990s presents clinicians and sexually active youth with many additional options. PMID- 2201854 TI - Chlamydia trachomatis infections in adolescents. AB - The guidelines of the Centers for Disease Control should be applied with appreciation of their limitations. The serious sequelae of chlamydial infections in young patients warrant vigorous antichlamydial therapy and specific microbiologic diagnosis. Until public health authorities implement control programs, the efforts of individual practitioners will probably be the mainstay of the flight against C. trachomatis. PMID- 2201855 TI - Adolescent suicide. AB - Suicide is a major public health problem among adolescents. Although the event is rare, and rates have stabilized and even shown slight reduction in recent years, suicide has nevertheless become the second leading cause of morbidity among youths aged 15 to 24, which is otherwise a robust and relatively disease-free population. Although research on predictive factors has yielded increasingly sensitive indices of who the high-risk adolescent might be, the inherent difficulty of predicting rare events from common ones has made sensitive and specific prediction most elusive. Current neurobiologic research holds promise for the use of biologic markers in the identification of high-risk adolescents, and pharmacologic research may yield further advances in the treatment of affectively disordered youths. At this point, the most promising approaches to treating adolescent suicide appear to be (1) treatment of disorders antecedent to suicide crises, such as depression, substance abuse, family conflict, and conduct disturbance, and (2) prevention efforts targeting known high-risk groups, such as affectively disordered young men with accompanying alcohol and drug involvement and other antisocial behavior. PMID- 2201856 TI - Adolescent chemical dependency. AB - Adolescent chemical dependency is now a recognized, diagnosable entity. In most respects, it mimics the diagnosis in adults. The practicing physician has some obligation to be familiar with changing trends in drug use and should have the skills to define problem use and assess risk. The physician should also address the issue as part of routine clinical interactions with patients and be aware of community resources for further assessment and treatment. Finally, the physician should be an advocate of the young patient and be helpful to parents in understanding the problem, but he or she should not be the parent's agent when asked to commit the adolescent for treatment or carry out drug abuse screening. The problem of adolescent substance abuse is a pre-eminent social problem. The problem must be addressed on many fronts. The role of the physician provides a key component of the solution. PMID- 2201857 TI - Management of obesity in adolescence. AB - A great deal of the discouragement about treating adolescents who are obese is related to the traditional treatment approaches. Obesity is a complex problem needing comprehensive treatment. Focusing on weight loss as a short-term goal is unreasonable because of individual variation in the physiologic potential to lose weight. Short-term goals and rewards are related to adopting daily habits that will lead to a decrease in energy storage in the long term. Support for changing habits and improving psychosocial adjustment is a necessary component of effective treatment, enabling patients and their families to make changes. PMID- 2201858 TI - Medical complications of anorexia nervosa and bulimia nervosa. AB - The internist plays a critical role in the care of eating disorder patients, especially in the management of the life-threatening medical complications of these conditions. In anorexia nervosa, the immediate danger is related to the effects of voluntary starvation, including hypophosphatemia, bone marrow failure, cardiac decompensation, and shock. Patients with bulimia nervosa more often experience severe fluid and electrolyte abnormalities resulting in hypovolemia, secondary hyperaldosteronism, depletion of total body potassium, and cardiac arrhythmias. Immediate management of medical complication and correction of nutritional deficits are necessary before patients can benefit from psychotherapy. The need for continued involvement of the internist in the ongoing care of the eating disorder patient is stressed. The high mortality and the likelihood of chronicity without early intervention underscore the need for early recognition and skilled management of eating disorders. PMID- 2201859 TI - Adolescents with closed head injury. Neuropsychological consequences. AB - Individuals in the adolescent age group are at particularly high risk for being involved in accidents. Closed head injury is a common consequence of motor vehicle crashes. As acute medical interventions are becoming more sophisticated and successful, more teenagers are surviving such accidents. However, cognitive deficits frequently result in weaknesses in intelligence, memory capacity, and abstract thinking. Such weaknesses can emerge in cases of mild head trauma as well. These cognitive deficits can have a profound impact on the adolescent's academic, social, and family functioning. PMID- 2201860 TI - Atherosclerosis during adolescence. AB - Interest in diseases of the arteries during the juvenile period is evident during the first half of this century. In the 1950s, it was clearly demonstrated that the early lesions of atherosclerosis were detectable in children and, especially, in adolescents. By the end of the 1960s, the scope of early atherosclerotic changes in the arteries of juveniles became firmly established. In the 1970s, the search for adult risk factors in juveniles began in earnest. In the 1980s, adult risk factors were identified in juveniles and correlated with pathologic changes. The therapeutic issues that involve life-long compliance in high-risk children and adolescents are unique to this age group. PMID- 2201861 TI - The function of protein carboxylmethyltransferase in eucaryotic cells. AB - Protein carboxylmethyltransferase (PCM) is an enzyme whose function in eucaryotic cells remains controversial. Early studies suggested that protein carboxylmethylation subserved a regulatory, post-translational role in such diverse processes as secretion, neuronal receptor function, chemotaxis, and cellular differentiation. Later work strongly supported a totally unrelated role for this enzyme, i.e., the repair of spontaneously altered aspartate residues in cellular proteins. More recent evidence, however, suggests that a distinct, membrane-associated PCM catalyzes the methylation of alpha-carboxyl groups of C terminal cysteines on discrete proteins. In view of these recent investigations, the data supporting a regulatory role for PCM are critically discussed and re evaluated. There now appears to be compelling evidence that PCM(s) subserves both repair and regulatory functions in eucaryotic cells, catalyzing post translational modifications of proteins involved in cell division, hormonal secretion, calmodulin-associated events and the interaction of guanyl nucleotide linked proteins with the cell membrane. PMID- 2201862 TI - An aminoboronic acid derivative inhibits thymopentin metabolism by mucosal membrane aminopeptidases. AB - Thymopentin is a pentapeptide with immunomodulatory activity. Transmucosal delivery may offer advantages over other routes, but published data have shown relatively poor efficacy when dosed nasally. Metabolism of thymopentin by the rat nasal mucosa and the effects of an aminoboronic acid aminopeptidase inhibitor, boroleucine, were evaluated. Thymopentin concentrations in a solution perfused through the isolated nasal cavity decayed with a first-order half-life of 12 minutes. Thymopentin was metabolized primarily by aminopeptidases, based on the amount of tetrapeptide metabolite formed. In the presence of boroleucine, at an inhibitor/substrate molar concentration ratio of 0.015/1, the degradation half life was prolonged to 37 minutes. Appearance of the tetrapeptide metabolite of aminopeptidases was delayed. Boroleucine and other aminoboronic acid peptidase inhibitors may be useful for improving thymopentin delivery. PMID- 2201863 TI - Hypoxia increases endothelin release in bovine endothelial cells in culture, but epinephrine, norepinephrine, serotonin, histamine and angiotensin II do not. AB - Calf coronary artery endothelial cells in culture were exposed to normoxic and hypoxic conditions (2% oxygen) for 4 hr and 24 hr. After 24 hr of incubation, there was a significant increase in the accumulation of immunoreactive endothelin (irET) in the media. Incubations with epinephrine, norepinephrine, serotonin, histamine and angiotensin II did not result in an increase in irET production. These studies indicate that hypoxia enhances endothelin release, however, the kinetics of this release suggest that the acute endothelium-dependent vasoconstriction occurring after hypoxia does not result from an increase in endothelin release. PMID- 2201864 TI - Stimulation of proteolysis on calmodulin. AB - The proteolysis of calmodulin by fungal protease (type XIX) was greatly enhanced in the presence of dGTP and MS2 RNA. Whereas, only moderate proteolytic activation on bacterial proteases (type XXVI) was observed in the presence of MS2 RNA. No appreciable proteolysis of calmodulin by bacterial protease (type IX) was observed. Proteolytic fragments of calmodulin cleaved by fungal protease exhibited unusual low mobility during SDS-polyacrylamide gel electrophoresis. Similar decreased electrophoretic mobility was also noted in the proteolytic fragments of other Ca2(+)-binding proteins including S-100A protein and parvalbumin. PMID- 2201865 TI - [Experimental automated system for studying spectral characteristics of tissues in reflected light]. AB - The authors describe a computer-equipped system for spectral examination of tissues during endoscopy. The system is used for evaluation of hemoglobin- and hydroxyhemoglobin tissue saturation and detection of pathological tissues. PMID- 2201866 TI - The 'Bayer bridges' confronted with results from improved electron microscopy methods. AB - In electron micrographs of conventionally prepared thin sections of Escherichia coli one observes (i) a wavy appearance of the two membranes showing frequent appositions (named adhesion sites) and (ii) intermembrane bridges after plasmolysis which, it is claimed, occur at the adhesion sites and are related to intermembrane protein transport (transmigration). When chemical fixation is replaced by cryofixation, the observations are very different. (a) The two membranes are equally spaced and no contacts, adhesions or other sorts of connections are visible. (b) After plasmolysis the protoplast is shrunken, but the typical bridges are no longer produced. (c) In addition, when peptidoglycan is stained on conventionally prepared sections, it is revealed as a 7-nm-thick sacculus which is not interrupted at the sites of apposition. In view of the new observations, the structural concepts derived from conventionally prepared material must be revised. It is proposed that the intermembrane space is entirely filled by a gel, the outer part of which is the 7 nm thick, very stable, chemically resistant peptidoglycan (or murein). The inner part is much less stable and is proposed to undergo rapid autolytic changes upon cell death. The large 'Bayer bridges' might then tentatively be explained as an artificial post mortem enhancement of either a stream of proteins transmigrating across the periplasm or of a pre-existing, but not yet resolved, structure. This enhancement probably occurs during the 7-10 min between plasmolysis and fixation that are prescribed for the procedure necessary for revealing 'Bayer bridges'. PMID- 2201867 TI - Genetic instability and hypervariability in Streptomyces ambofaciens: towards an understanding of a mechanism of genome plasticity. AB - Many Streptomyces species exhibit a very high degree of genetic instability which is usually manifested as genomic rearrangements such as large deletions. In Streptomyces ambofaciens DSM40697, two levels of genetic instability were previously described: (i) a basic genetic instability similar to that reported for other strains, and (ii) hypervariability, a phenomenon that we believe to be a new aspect of instability closely associated with DNA amplification. A large DNA region undergoes deletions, amplifications and large genomic changes strictly associated with both aspects of genetic instability. The genetic and molecular analyses of the different aspects of genetic instability allow us to propose that they result from a cascade of molecular events and to investigate the relationships between genetic instability phenomena and genome fluidity. PMID- 2201868 TI - The arcB gene of Escherichia coli encodes a sensor-regulator protein for anaerobic repression of the arc modulon. AB - The arcA (dye) and arcB genes of Escherichia coli are responsible for anaerobic repression of target operons and regulons of aerobic function (the arc modulon). The amino acid sequence of ArcA (Dye) indicated that it is the regulator protein of a two-component control system. Here we show that ArcB is a membrane sensor protein on the basis of its deduced amino acid sequence (778 residues), hydropathicity profile, and cellular distribution. On the carboxyl end of the ArcB sequence there is an additional domain showing homology with conserved regions of regulator proteins. Deletion into this domain destroyed ArcB function. ArcB conserved a histidine residue for autophosphorylation of the sensor proteins, and aspartic residues important for the regulator proteins. PMID- 2201869 TI - Chromosome-specific identification and quantification of S1 nuclease-sensitive sites in yeast chromatin by pulsed-field gel electrophoresis. AB - Sites that are sensitive to the single-strand-specific endonuclease S1 ('S1 sensitive sites', SSS) occur in native chromatin and, like DNA double-stranded breaks (DSB), they are induced by DNA-damaging agents, such as ionizing radiation. We have developed a method to quantify SSS and DSB in yeast chromatin by using pulsed-field gel electrophoresis (PFGE) to separate the intact chromosomal-length DNA molecules from the lower molecular-weight broken ones. Direct evaluation of the photonegatives of the ethidium bromide-stained gels by laser densitometry enabled us to calculate the numbers of DSB and SSS per DNA molecule. These numbers were determined from the bulk of the non-separated genomic DNA of yeast, corresponding to a single band in the PFGE (pulse time 10 seconds), and in each of the eight largest yeast chromosomes, corresponding to distinct bands in the PFGE gels (pulse time 50 seconds), which were not superimposed by the smear of the broken, low molecular-weight DNA. Furthermore, the induction of DSB and SSS in a specific chromosome (circular chromosome III) was determined by Southern hybridization of the PFGE gels with a suitable centromere probe, followed by densitometry of the autoradiographs. Our method allows the chromosome-specific monitoring of DSB and all those DNA structures that are processed either in vivo or in vitro into DSB and which may not be distributed randomly within the genome. PMID- 2201870 TI - The complete nucleotide sequence of the Pasteurella multocida toxin gene and evidence for a transcriptional repressor, TxaR. AB - The osteolytic toxin of Pasteurella multocida induces bone resorption in vivo and in vitro (Foged et al., 1988; Kimman et al., 1987). In this report the toxin encoding toxA gene is sequenced, and the deduced primary structure of the toxin shows a protein of 1285 amino acids, containing a striking homology to a metal binding motif. Evidence that expression of the toxA gene is repressed at a transcriptional level in Escherichia coli is presented. Repression could be abolished either by deletion of a region upstream of toxA, or by a putative frame shift mutation in the same region. The repressor protein encoded within this region was efficient in trans, and was named TxaR. PMID- 2201871 TI - An inversion truncating the creA gene of Aspergillus nidulans results in carbon catabolite derepression. AB - The creAd-30 mutation leading to carbon catabolite derepression in Aspergillus nidulans is a pericentric inversion, having one breakpoint within the creA gene on the left arm of chromosome I and the other breakpoint between binG and yA on the right arm. The left-arm breakpoint alters the creA transcript. The likelihood that the inversion truncates creA centrally strengthens a previous proposal that derepression is the phenotype of loss-of-function mutations in creA. PMID- 2201873 TI - Applications of avidin-biotin technology: literature survey. PMID- 2201872 TI - Biotinidase. PMID- 2201874 TI - Avidin- and streptavidin-containing probes. PMID- 2201875 TI - Enzymatic and radioactive assays for biotin, avidin, and streptavidin. PMID- 2201877 TI - Avidin-biotin technology. Reflections. PMID- 2201876 TI - Sequential solid-phase assay for biotin based on 125I-labeled avidin. PMID- 2201878 TI - Immunoselective cell separation. PMID- 2201879 TI - Immunocytochemical detection of human T- and B-cell antigens. PMID- 2201880 TI - Streptavidin-enzyme complexes in detection of antigens on western blots. PMID- 2201881 TI - Avidin-biotin mediated immunoassays: overview. PMID- 2201882 TI - Avidin-biotin system in enzyme immunoassays. PMID- 2201883 TI - Biotin-binding proteins: overview and prospects. PMID- 2201885 TI - Slide immunoenzymatic assay for human immunoglobulin E. PMID- 2201884 TI - Introduction to avidin-biotin technology. PMID- 2201886 TI - Colorimetric-detected DNA sequencing. PMID- 2201887 TI - Modern reproductive technologies in the treatment of infertility. PMID- 2201888 TI - Evening primrose oil and treatment of premenstrual syndrome. AB - The therapeutic effectiveness of evening primrose oil (Efamol, Vita-Glow) in the relief of 10 symptoms associated with premenstrual syndrome (PMS) as well as menstrual symptoms was studied in 38 women. The prospective trial was randomised, double-blind and placebo-controlled and was crossed-over after three cycles. Although the results showed an improvement in symptoms of PMS during the trial, no significant differences in the scoring between the active and placebo groups were found over six cycles. No "carry-over" effect of active medication was observed; the beneficial effect on all symptoms (psychological, fluid retention, breast) was rapid, the scores decreasing in the first cycle but increasing slightly at the change-over period after the third cycle, irrespective of whether the active or placebo medication was next given. These findings indicate that the improvement experienced by these women with moderate PMS was solely a placebo effect. PMID- 2201890 TI - 1990-1991 MSMA membership directory. Missouri State Medical Association. PMID- 2201889 TI - Withdrawing and withholding treatment in intensive care. Part 1. Social and ethical dimensions. AB - Intensive care is an expensive resource. The medical profession has been criticised for applying technology indiscriminately and at vast expense to a relatively small group of patients. The desire of governments to reduce the cost of health care has made rationing of health services a topic of open discussion rather than an implicit activity as it has been in the past. The appropriate response of doctors to these problems is to provide leadership in promoting public awareness and debate of the effects of rationing, and to provide rational allocation of therapy to individual patients. The major issues involving resource allocation in society and to individuals are discussed. PMID- 2201891 TI - Tc, an unusual promoter element required for constitutive transcription of the yeast HIS3 gene. AB - Tc is the proximal promoter element required for constitutive his3 transcription that occurs in the absence of the canonical TATA element (TR) and is initiated from the +1 site. The TC element, unlike TR, does not respond to transcriptional stimulation by the GCN4 or GAL4 activator protein. Analysis of deletion, substitution, and point mutations indicates that Tc mapped between nucleotides 54 and -83 and is a sequence-dependent element because it could not be functionally replaced by other DNA sequences. However, in contrast to the behavior of typical promoter elements, it was surprisingly difficult to eliminate Tc function by base pair substitutions. Of 15 derivatives averaging four substitutions in the Tc region and representing 40% of all possible single changes, only 1 inactivated the Tc element. Moreover, the phenotypes of mutant and hybrid elements indicated that inactivation of Tc required multiple changes. The spacing between Tc and the initiation region could be varied over a 30-base pair range without significantly affecting the level of transcription from the +1 site. From these results, we consider it possible that Tc may not interact with TFIID or some other typical sequence-specific transcription factor, but instead might influence transcription, either directly or indirectly, by its DNA structure. PMID- 2201892 TI - Expression and function of a human initiator tRNA gene in the yeast Saccharomyces cerevisiae. AB - We showed previously that the human initiator tRNA gene, in the context of its own 5'- and 3'-flanking sequences, was not expressed in Saccharomyces cerevisiae. Here we show that switching its 5'-flanking sequence with that of a yeast arginine tRNA gene allows its functional expression in yeast cells. The human initiator tRNA coding sequence was either cloned downstream of the yeast arginine tRNA gene, with various lengths of intergenic spacer separating them, or linked directly to the 5'-flanking sequence of the yeast arginine tRNA coding sequence. The human initiator tRNA made in yeast cells can be aminoacylated with methionine, and it was clearly separated from the yeast initiator and elongator methionine tRNAs by RPC-5 column chromatography. It was also functional in yeast cells. Expression of the human initiator tRNA in transformants of a slow-growing mutant yeast strain, in which three of the four endogenous initiator tRNA genes had been inactivated by gene disruption, resulted in enhancement of the growth rate. The degree of growth rate enhancement correlated with the steady-state levels of human tRNA in the transformants. Besides providing a possible assay for in vivo function of mutant human initiator tRNAs, this work represents the only example of the functional expression of a vertebrate RNA polymerase III transcribed gene in yeast cells. PMID- 2201894 TI - Isolation of the URA5 gene from Cryptococcus neoformans var. neoformans and its use as a selective marker for transformation. AB - A cDNA encoding Cryptococcus neoformans orotidine monophosphate pyrophosphorylase (OMPPase) has been isolated by complementation of the cognate Escherichia coli pyrE mutant. The cDNA was used as a probe to isolate a genomic DNA fragment encoding the OMPPase gene (URA5). By using electroporation for the introduction of plasmid DNA containing the URA5 gene, C. neoformans ura5 mutants could be transformed at low efficiency. Ura+ transformants obtained with supercoiled plasmids containing the URA5 gene showed marked mitotic instability and contained extrachromosomal URA5 sequences, suggesting limited ability to replicate within C. neoformans. Transformants obtained with linear DNA were of two classes: stable transformants with integrated URA5 sequences, and unstable transformants with extrachromosomal URA5 sequences. PMID- 2201893 TI - Glucose-induced hyperaccumulation of cyclic AMP and defective glucose repression in yeast strains with reduced activity of cyclic AMP-dependent protein kinase. AB - Addition of glucose or related fermentable sugars to derepressed cells of the yeast Saccharomyces cerevisiae triggers a RAS-mediated cyclic AMP (cAMP) signal that induces a protein phosphorylation cascade. In yeast mutants (tpk1w1, tpk2w1, and tpk3w1) containing reduced activity of cAMP-dependent protein kinase, fermentable sugars, as opposed to nonfermentable carbon sources, induced a permanent hyperaccumulation of cAMP. This finding confirms previous conclusions that fermentable sugars are specific stimulators of cAMP synthesis in yeast cells. Despite the huge cAMP levels present in these mutants, deletion of the gene (BCY1) coding for the regulatory subunit of cAMP-dependent protein kinase severely reduced hyperaccumulation of cAMP. Glucose-induced hyperaccumulation of cAMP was also observed in exponential-phase glucose-grown cells of the tpklw1 and tpk2w1 strains but not the tpk3w1 strain even though addition of glucose to glucose-repressed wild-type cells did not induce a cAMP signal. Investigation of mitochondrial respiration by in vivo 31P nuclear magnetic resonance spectroscopy showed the tpk1w1 and tpk2w1 strains, to be defective in glucose repression. These results are consistent with the idea that the signal transmission pathway from glucose to adenyl cyclase contains a glucose-repressible protein. They also show that a certain level of cAMP-dependent protein phosphorylation is required for glucose repression. Investigation of the glucose-induced cAMP signal and glucose-induced activation of trehalase in derepressed cells of strains containing only one of the wild-type TPK genes indicates that the transient nature of the cAMP signal is due to feedback inhibition by cAMP-dependent protein kinase. PMID- 2201895 TI - Transforming growth factor alpha in arterioles: cell surface processing of its precursor by elastases. AB - Analysis of the transforming growth factor alpha (TGF alpha) cDNA predicts that the mature TGF alpha polypeptide is cleaved from the extracellular domain of its precursor, which is an integral membrane protein. Furthermore, the cleavage sites for the release of this mitogen are compatible with the participation of an elastaselike protease. We have immunohistochemically localized TGF alpha to the vascular smooth muscle cells in the arterioles. To investigate whether polymorphonuclear (PMN) leukocytic elastase, a blood-borne protease, could process the cell surface TGF alpha, NR6 cells were transfected with the rat TGF alpha cDNA. The cDNA encoded the entire open reading frame, and its expression was under the control of the mouse metallothionein I promoter. A cloned transfectant, termed 1B2, synthesized the TGF alpha precursor in a zinc-inducible manner, and the precursor was localized to the cell surface. Western blot (immunoblot) analysis indicated that treatment of the zinc-induced 1B2 cells with either PMN leukocytic or pancreatic elastase resulted in the release of the mature TGF alpha polypeptide. The released TGF alpha was bioactive, as it was capable of both competing with epidermal growth factor for binding to its receptor and stimulating [3H]thymidine incorporation in the mitogenic assay. Formaldehyde fixation of the 1B2 cells eliminated basal release of TGF alpha but allowed normal processing by both PMN leukocytic and pancreatic elastase to occur. However, human cathepsin G, bovine pancreatic alpha 1-chymotrypsin, collagenase, trypsin, subtilisin, and plasmin failed to release any detectable fragments of the TGF alpha precursor from the fixed cells. The location of TGF alpha in the arterioles and ability of PMN leukocytic elastase to process the membrane-bound TGF alpha precursor suggests a novel role for this elastase at the wound site. PMID- 2201896 TI - The Saccharomyces cerevisiae DPM1 gene encoding dolichol-phosphate-mannose synthase is able to complement a glycosylation-defective mammalian cell line. AB - The Saccharomyces cerevisiae DPM1 gene product, dolichol-phosphate-mannose (Dol-P Man) synthase, is involved in the coupled processes of synthesis and membrane translocation of Dol-P-Man. Dol-P-Man is the lipid-linked sugar donor of the last four mannose residues that are added to the core oligosaccharide transferred to protein during N-linked glycosylation in the endoplasmic reticulum. We present evidence that the S. cerevisiae gene DPM1, when stably transfected into a mutant Chinese hamster ovary cell line, B4-2-1, is able to correct the glycosylation defect of the cells. Evidence for complementation includes (i) fluorescence activated cell sorter analysis of differential lectin binding to cell surface glycoproteins, (ii) restoration of Dol-P-Man synthase enzymatic activity in crude cell lysates, (iii) isolation and high-performance liquid chromatography fractionation of the lipid-linked oligosaccharides synthesized in the transfected and control cell lines, and (iv) the restoration of endoglycosidase H sensitivity to the oligosaccharides transferred to a specific glycoprotein synthesized in the DPM1 CHO transfectants. Indirect immunofluorescence with a primary antibody directed against the DPM1 protein shows a reticular staining pattern of protein localization in transfected hamster and monkey cell lines. PMID- 2201897 TI - Phosphorylated forms of GAL4 are correlated with ability to activate transcription. AB - GAL4I, GAL4II, and GAL4III are three forms of the yeast transcriptional activator protein that are readily distinguished on the basis of electrophoretic mobility during sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Phosphorylation accounts for the reduced mobility of the slowest-migrating form, GAL4III, which is found to be closely associated with high-level GAL/MEL gene expression (L. Mylin, P. Bhat, and J. Hopper, Genes Dev. 3:1157-1165, 1989). Here we show that GAL4II, like GAL4III, can be converted to GAL4I by phosphatase treatment, suggesting that in vivo GAL4II is derived from GAL4I by phosphorylation. We found that cells which overproduced GAL4 under conditions in which it drove moderate to low levels of GAL/MEL gene expression showed only forms GAL4I and GAL4II. To distinguish which forms of GAL4 (GAL4I, GAL4II, or both) might be responsible for transcription activation in the absence of GAL4III, we performed immunoblot analysis on UASgal-binding-competent GAL4 proteins from four gal4 missense mutants selected for their inability to activate transcription (M. Johnston and J. Dover, Proc. Natl. Acad. Sci. USA 84:2401-2405, 1987; Genetics 120;63-74, 1988). The three mutants with no detectable GAL1 expression did not appear to form GAL4II or GAL4III, but revertants in which GAL4-dependent transcription was restored did display GAL4II- or GAL4III-like electrophoretic species. Detection of GAL4II in a UASgal-binding mutant suggests that neither UASgal binding nor GAL/MEL gene activation is required for the formation of GAL4II. Overall, our results imply that GAL4I may be inactive in transcriptional activation, whereas GAL4II appears to be active. In light of this work, we hypothesize that phosphorylation of GAL4I makes it competent to activate transcription. PMID- 2201898 TI - Characterization of yeast Vps33p, a protein required for vacuolar protein sorting and vacuole biogenesis. AB - vps33 mutants missort and secrete multiple vacuolar hydrolases and exhibit extreme defects in vacuolar morphology. Toward a molecular understanding of the role of the VPS33 gene in vacuole biogenesis, we have cloned this gene from a yeast genomic library by complementation of a temperature-sensitive vps33 mutation. Gene disruption demonstrated that VPS33 was not essential but was required for growth at high temperatures. At the permissive temperature, vps33 null mutants exhibited defects in vacuolar protein localization and vacuole morphology similar to those seen in most of the original mutant alleles. Sequence analysis revealed a putative open reading frame sufficient to encode a protein of 691 amino acids. Hydropathy analysis indicated that the deduced product of the VPS33 gene is generally hydrophilic, contains no obvious signal sequence or transmembrane domains, and is therefore unlikely to enter the secretory pathway. Polyclonal antisera raised against TrpE-Vps33 fusion proteins recognized a protein in yeast cells of the expected molecular weight, approximately 75,000. In cell fractionation studies, Vps33p behaved as a cytosolic protein. The predicted VPS33 gene product possessed sequence similarity with a number of ATPases and ATP binding proteins specifically in their ATP-binding domains. One vps33 temperature sensitive mutant contained a missense mutation near this region of sequence similarity; the mutation resulted in a Leu-646----Pro substitution in Vps33p. This temperature-sensitive mutant strain contained normal vacuoles at the permissive temperature but lacked vacuoles specifically in the bud at the nonpermissive temperature. Our data suggest that Vps33p acts in the cytoplasm to facilitate Golgi-to-vacuole protein delivery. We propose that as a consequence of the vps33 protein-sorting defects, abnormalities in vacuolar morphology and vacuole assembly result. PMID- 2201899 TI - Differential repair of UV damage in rad mutants of Saccharomyces cerevisiae: a possible function of G2 arrest upon UV irradiation. AB - After UV irradiation, the transcriptionally active MAT alpha locus in Saccharomyces cerevisiae is preferentially repaired compared with the inactive HML alpha locus. The effect of rad mutations from three different epistasis groups on differential repair was investigated. Three mutants, rad9, rad16, and rad24, were impaired in the removal of UV dimers from the inactive HML alpha locus, whereas they had generally normal repair of the active MAT alpha locus. Since RAD9 is necessary for G2 arrest after UV irradiation, we propose that the G2 stage plays a role in making the dimers accessible for repair, at least in the repressed HML alpha locus. PMID- 2201900 TI - The RPC31 gene of Saccharomyces cerevisiae encodes a subunit of RNA polymerase C (III) with an acidic tail. AB - The RPC31 gene encoding the C31 subunit of Saccharomyces cerevisiae RNA polymerase C (III) has been isolated, starting from a C-terminal fragment cloned on a lambda gt11 library. It is unique on the yeast genome and lies on the left arm of chromosome XIV, very close to a NotI site. Its coding sequence perfectly matches the amino acid sequence of two oligopeptides prepared from purified C31. It is also identical to the ACP2 gene previously described as encoding an HMG1 like protein (W. Haggren and D. Kolodrubetz, Mol. Cell. Biol. 8:1282-1289, 1988). Thus, ACP2 and RPC31 are allelic and encode a subunit of RNA polymerase C. The c31 protein has a highly acidic C-terminal tail also found in several other chromatin-interacting proteins, including animal HMG1. Outside this domain, however, there is no appreciable homology to any known protein. The growth phenotypes of a gene deletion, of insertions, and of nonsense mutations indicate that the C31 protein is strictly required for cell growth and that most of the acidic domain is essential for its function. Random mutagenesis failed to yield temperature-sensitive mutants, but a slowly growing mutant was constructed by partial suppression of a UAA nonsense allele of RPC31. Its reduced rate of tRNA synthesis in vivo relative to 5.8S rRNA supports the hypothesis that the C31 protein is a functional subunit of RNA polymerase C. PMID- 2201901 TI - The N-terminal TPR region is the functional domain of SSN6, a nuclear phosphoprotein of Saccharomyces cerevisiae. AB - The SSN6 protein functions as a negative regulator of a variety of genes in Saccharomyces cerevisiae and is required for normal growth, mating, and sporulation. It is a member of a family defined by a repeated amino acid sequence, the TPR (tetratricopeptide repeat) motif. Here, we have used specific antibody to identify and characterize the SSN6 protein. Both SSN6 and a bifunctional SSN6-beta-galactosidase fusion protein were localized in the nucleus by immunofluorescence staining. The N-terminal one-third of the protein containing the TPR units was identified as the region that is important for SSN6 function. Analysis of four nonsense alleles, isolated as intragenic suppressors of an ssn6::URA3 insertion, revealed that polypeptides truncated after TPR unit 7 provide SSN6 function. Deletion analysis suggested that TPR units are required but that 4 of the 10 TPR units are sufficient. In addition, deletion studies indicated that three very long, homogeneous tracts of polyglutamine and poly(glutamine-alanine) are dispensable. Previous genetic evidence suggested the SSN6 protein as a possible target of the SNF1 protein kinase. Here, we show that the C terminus of SSN6 is phosphorylated in vivo and that the SNF1 kinase is not responsible for most of the phosphorylation. Finally, SSN6 has a modest effect on the maintenance of minichromosomes. PMID- 2201902 TI - Two systems of glucose repression of the GAL1 promoter in Saccharomyces cerevisiae. AB - Expression of the GAL1 gene in Saccharomyces cerevisiae is strongly repressed by growth on glucose. We show that two sites within the GAL1 promoter mediate glucose repression. First, glucose inhibits transcription activation by GAL4 protein through UASG. Second, a promoter element, termed URSG, confers glucose repression independently of GAL4. We have localized the URSG sequences responsible for glucose repression to an 87-base-pair fragment located between UASG and the TATA box. Promoters deleted for small (20-base-pair) segments that span this sequence are still subject to glucose repression, suggesting that there are multiple sequences within this region that confer repression. Extended deletions across this region confirm that it contains at least two and possibly three URSG elements. To identify the gene products that confer repression upon UASG and URSG, we have analyzed glucose repression mutants and found that the GAL83, REG1, GRR1, and SSN6 genes are required for repression mediated by both UASG and URSG. In contrast, GAL82 and HXK2 are required only for UASG repression. A mutation designated urr1-1 (URSG repression resistant) was identified that specifically relieves URSG repression without affecting UASG repression. In addition, we observed that the SNF1-encoded protein kinase is essential for derepression of both UASG and URSG. We propose that repression of UASG and URSG is mediated by two independent pathways that respond to a common signal generated by growth on glucose. PMID- 2201903 TI - K28, a unique double-stranded RNA killer virus of Saccharomyces cerevisiae. AB - The double-stranded RNA (dsRNA) viruses of Saccharomyces cerevisiae consist of 4.5-kilobase-pair (kb) L species and 1.7- to 2.1-kb M species, both found in cytoplasmic viruslike particles (VLPs). The L species encode their own capsid protein, and one (LA) has been shown to encode a putative capsid-polymerase fusion protein (cap-pol) that presumably provides VLPs with their transcriptase and replicase functions. The M1 and M2 dsRNAs encode the K1 and K2 toxins and specific immunity mechanisms. Maintenance of M1 and M2 is dependent on the presence of LA, which provides capsid and cap-pol for M dsRNA maintenance. Although a number of different S. cerevisiae killers have been described, only K1 and K2 have been studied in any detail. Their secreted polypeptide toxins disrupt cytoplasmic membrane functions in sensitive yeast cells. K28, named for the wine S. cerevisiae strain 28, appears to be unique; its toxin is unusually stable and disrupts DNA synthesis in sensitive cells. We have now demonstrated that 4.5-kb L28 and 2.1-kb M28 dsRNAs can be isolated from strain 28 in typical VLPs, that these VLPs are sufficient to confer K28 toxin and immunity phenotypes on transfected spheroplasts, and that the immunity of the transfectants is distinct from that of either M1 or M2. In vitro transcripts from the M28 VLPs show no cross-hybridization to denatured M1 or M2 dsRNAs, while L28 is an LA species competent for maintenance of M1. K28, encoded by M28, is thus the third unique killer system in S. cerevisiae to be clearly defined. It is now amenable to genetic analysis in standard laboratory strains. PMID- 2201904 TI - Sequences within an upstream activation site in the yeast enolase gene ENO2 modulate repression of ENO2 expression in strains carrying a null mutation in the positive regulatory gene GCR1. AB - Transcription of the yeast enolase gene ENO2 is reduced 20- to 50-fold in strains carrying a null mutation in the positive regulatory gene GCR1. A small deletion mutation within one of two upstream activation sites (UAS elements) in the 5' flanking region of ENO2 permitted wild-type levels of ENO2 gene expression in a strain carrying the gcr1 null mutation. These data show that sequences required for UAS element activity in GCR1 strains were required to repress ENO2 expression in a gcr1 strain. Protein factors that specifically bound to this UAS/repression site were identified. We show that the DNA-binding protein ABFI (autonomously replicating sequence-binding factor) is the major protein which binds the UAS/repression site. Minor DNA-binding activities that interact specifically with the UAS/repression site were also identified and may correspond to proteolytic breakdown products of ABFI. None of the observed binding activities were encoded by the GCR1 structural gene. A double-stranded oligonucleotide that included the UAS/repression site activated transcription of UAS-less ENO1 and ENO2 gene cassettes in vivo to wild-type levels in strains carrying the GCR1 allele as well as the gcr1 null mutation. These latter data show that the UAS/repression site is sufficient for transcriptional activation but is not sufficient to repress transcription of the enolase genes in a gcr1 genetic background. PMID- 2201905 TI - Multiple factors bind the upstream activation sites of the yeast enolase genes ENO1 and ENO2: ABFI protein, like repressor activator protein RAP1, binds cis acting sequences which modulate repression or activation of transcription. AB - Binding sites for three distinct proteins were mapped within the upstream activation sites (UAS) of the yeast enolase genes ENO1 and ENO2. Sequences that overlapped the UAS1 elements of both enolase genes bound a protein which was identified as the product of the RAP1 regulatory gene. Sequences within the UAS2 element of the ENO2 gene bound a second protein which corresponded to the ABFI (autonomously replicating sequence-binding factor) protein. A protein designated EBF1 (enolase-binding factor) bound to sequences which overlapped the UAS2 element in ENO1. There was a good correlation among all of the factor-binding sites and the location of sequences required for UAS activity identified by deletion mapping analysis. This observation suggested that the three factors play a role in transcriptional activation of the enolase genes. UAS elements which bound the RAP1 protein or the ABFI protein modulated glucose-dependent induction of ENO1 and ENO2 expression. The ABFI-binding site in ENO2 overlapped sequences required for UAS2 activity in wild-type strains and for repression of ENO2 expression in strains carrying a null mutation in the positive regulatory gene GCR1. These latter results showed that the ABFI protein, like the RAP1 protein, bound sequences required for positive as well as negative regulation of gene expression. These observations strongly suggest that the biological functions of the RAP1 and ABFI proteins are similar. PMID- 2201906 TI - An initiation zone of chromosomal DNA replication located upstream of the c-myc gene in proliferating HeLa cells. AB - Studies on origins of DNA replication in mammalian cells have long been hampered by a lack of methods sensitive enough for the localization of such origins in chromosomal DNA. We have employed a new method for mapping origins, based on polymerase chain reaction amplification of nascent strand segments, to examine replication initiated in vivo near the c-myc gene in human cells. Nascent DNA, pulse-labeled in unsynchronized HeLa cells, was size fractionated and purified by immunoprecipitation with anti-bromodeoxyuridine antibodies. Lengths of the nascent strands that allow polymerase chain reaction amplification were determined by hybridization to probes homologous to amplified segments and used to calculate the position of the origin. We found that DNA replication through the c-myc gene initiates in a zone centered approximately 1.5 kilobases upstream of exon I. Replication proceeds bidirectionally from the origin, as indicated by comparison of hybridization patterns for three amplified segments. The initiation zone includes segments of the c-myc locus previously reported to drive autonomous replication of plasmids in human cells. PMID- 2201907 TI - A conserved sequence in histone H2A which is a ubiquitination site in higher eucaryotes is not required for growth in Saccharomyces cerevisiae. AB - Histones H2A and H2B are modified by ubiquitination of specific lysine residues in higher and lower eucaryotes. To identify functions of ubiquitinated histone H2A, we studied an organism in which genetic analysis of histones is feasible, the yeast Saccharomyces cerevisiae. Surprisingly, immunoblotting experiments using both anti-ubiquitin and anti-H2A antibodies gave no evidence that S. cerevisiae contains ubiquitinated histone H2A. The immunoblot detected a variety of other ubiquitinated species. A sequence of five residues in S. cerevisiae histone H2A that is identical to the site of H2A ubiquitination in higher eucaryotes was mutated to substitute arginines for lysines. Any ubiquitination at this site would be prevented by these mutations. Yeast organisms carrying this mutation were indistinguishable from the wild type under a variety of conditions. Thus, despite the existence in S. cerevisiae of several gene products, such as RAD6 and CDC34, which are capable of ubiquitinating histone H2A in vitro, ubiquitinated histone H2A is either scarce in or absent from S. cerevisiae. Furthermore, the histone H2A sequence which serves as a ubiquitination site in higher eucaryotes is not essential for yeast growth, sporulation, or resistance to either heat stress or UV radiation. PMID- 2201908 TI - SPT6, an essential gene that affects transcription in Saccharomyces cerevisiae, encodes a nuclear protein with an extremely acidic amino terminus. AB - SPT6 is an essential gene of Saccharomyces cerevisiae that appears to play a role in transcription. Mutations in the SPT6 (SSN20, CRE2) gene suppress delta insertion mutations in the 5' regions of HIS4 and LYS2 and mutations in cis- and/or trans-acting elements that are required for expression of SUC2 and ADH2. We report here that SPT6 encodes a 170-kilodalton highly charged protein with an extremely acidic amino terminus. By use of an epitope-tagged SPT6 protein, we have determined by indirect immunofluorescence that the SPT6 protein is located in the nucleus. PMID- 2201910 TI - Domains of human c-myc protein required for autosuppression and cooperation with ras oncogenes are overlapping. AB - Amino acids 106 to 143 and 354 to 433 of the human c-myc protein (439 amino acids) were shown to be required for the protein to suppress c-myc gene transcription and were found to exactly overlap with those necessary for c-myc to cooperate with ras oncogenes in the transformation of rat embryo fibroblasts. The essential carboxyl-terminal region harbors structural motifs (a basic region, a helix-loop-helix motif, and a "leucine zipper"), which, in other proteins, can mediate dimerization and sequence-specific DNA binding. PMID- 2201909 TI - Sequence requirements in different steps of the pre-mRNA splicing reaction: analysis by the RNA modification-exclusion technique. AB - The stepwise assembly of splicing complexes and the subsequent splicing reaction were analyzed by the RNA modification-exclusion technique, which generates the equivalent of a complete set of point mutations in a single reaction. We found that although the sequences surrounding the 5' splice site, the branch point, and the 3' splice site, including the 3' AG, were required for presplicing complex formation, modified nucleotides at these positions were not completely excluded. The same sequences were required for splicing complex formation; however, modified nucleotides in these sequences were excluded to a much greater extent. PMID- 2201912 TI - Genotoxic effect of a keto-aldehyde produced by thermal degradation of reducing sugars. AB - Reductone (HOCH2-CO-CHO), a keto-aldehyde formed, in alkaline pH, by thermal degradation of reducing sugars, blocks cellular respiration and macromolecular biosynthesis, inactivates far-UV (254 nm)-irradiated wild-type E. coli cells, and causes DNA strand breaks. So it may be supposed to be an inducer of SOS functions. Indeed, when Salmonella tester strains TA98, TA100 and TA102 were treated with reductone solutions, without metabolization, a mutagenic effect was detected for all of them. Besides, reductone induced lysogenic E. coli cells and cell filamentation, as measured by the Inductest and the SOS Chromotest. So reductone must be considered a genotoxic drug. PMID- 2201911 TI - A short, highly repetitive element in intron -1 of the human c-Ha-ras gene acts as a block to transcriptional readthrough by a viral promoter. AB - We have identified a short, highly repetitive element within intron -1 of the human c-Ha-ras gene. This element was found to be transcribed in both orientations and to be homologous to heterogeneous nonpolyadenylated transcripts. The repetitive element blocked transcriptional readthrough from a strong upstream viral promoter but allowed unimpaired readthrough from the c-Has-ras promoter. We suggest that it may serve to prevent excessive transcription into the coding region of the gene under such circumstances as viral insertion. PMID- 2201913 TI - Genotoxic, mutagenic and recombinogenic effects of rauwolfia alkaloids. AB - In the last decade, the possible correlation between the use of reserpine and rauwolfia drugs as antihypertensive agents and breast cancer incidence has been investigated. For the purpose of evaluating the mutagenic and genotoxic effects of these drugs, reserpine and ajmalicine were studied using the SOS Chromotest and the induction of gene conversion, crossing-over and reverse mutation in the yeast diploid strain XS2316. The results indicated a lack of genotoxic, mutagenic and recombinogenic effects. PMID- 2201914 TI - Insulin effects in denervated and non-weight-bearing rat soleus muscle. AB - Previous reports indicated that glucose uptake in denervated muscle is resistant to insulin, while in non-weight-bearing (unweighted) muscle this effect of insulin is enhanced. To extend the comparison of these differences, insulin effects on amino acid uptake and protein metabolism were studied in soleus muscles subjected to denervation or unweighting. Denervated muscle showed insulin resistance of both 2-deoxy[1,2-3H]glucose and alpha-[methyl-3H]aminoisobutyric acid uptake whereas unweighted muscle showed an increased or normal response, respectively. Atrophy was greater in denervated than in unweighted muscle, apparently due to faster protein degradation. The stimulation of protein synthesis and the inhibition of protein degradation by insulin was generally less in denervated than in unweighted muscle. Since metabolic measurements in denervated-unweighted muscles did not differ from those in denervated-weight bearing muscles, effects of denervation must be independent of leg posture. PMID- 2201915 TI - Prognostic subgroups in B-cell chronic lymphocytic leukemia defined by specific chromosomal abnormalities. AB - BACKGROUND AND METHODS: Specific chromosomal abnormalities have been shown to affect the overall survival of patients with acute leukemia, but the possibility that specific chromosomal defects may influence the course of B-cell chronic lymphocytic leukemia (CLL) is controversial. We assessed this possibility as follows: blood mononuclear cells from 433 patients with B-cell CLL in five European centers were cultured with B-cell mitogens, and banded metaphases were studied. RESULTS: Three hundred ninety-one patients could be evaluated cytogenetically, and 218 had clonal chromosomal changes. The most common abnormalities were trisomy 12 (n = 67) and structural abnormalities of chromosome 13 (n = 51; most involving the site of the retinoblastoma gene) and of chromosome 14 (n = 41). Patients with a normal karyotype had a median overall survival of more than 15 years, in contrast to 7.7 years for patients with clonal changes. Patients with single abnormalities (n = 113) did better than those with complex karyotypes (P less than 0.001). Patients with abnormalities involving chromosome 14q had poorer survival than those with aberrations of chromosome 13q (P less than 0.05). Among patients with single abnormalities, those with trisomy 12 alone had poorer survival than patients with single aberrations of chromosome 13q (P = 0.01); the latter had the same survival as those with a normal karyotype. A high percentage of cells in metaphase with chromosomal abnormalities, indicating highly proliferative leukemic cells, was associated with poor survival (P less than 0.001). Cox proportional-hazards analysis identified age, sex, the percentage of cells in metaphase with chromosomal abnormalities, and the clinical stage of the disease (Binet classification system) as independent prognostic variables. CONCLUSIONS: Chromosomal analysis provides prognostic information about overall survival in addition to that supplied by clinical data in patients with B-cell CLL. PMID- 2201916 TI - Total hip and total knee replacement (1). PMID- 2201917 TI - Governmental bureaucracy in the nursing home. PMID- 2201918 TI - Production of yeast killer toxin in experimentally infected animals. AB - The ability of a killer yeast (Pichia anomala, UCSC 25F) to produce toxin in vivo was demonstrated, for the first time, in tissues of normal and immunosuppressed experimentally infected mice by means of a fluorescent antibody technique and a killer toxin specific monoclonal antibody. The possible significance of the findings is discussed. PMID- 2201919 TI - AIDS testing. Trial approved for saliva test. PMID- 2201920 TI - Oncoproteins. GAPs in understanding Ras. PMID- 2201921 TI - Stimulation of p21ras upon T-cell activation. AB - External signals that control the activity of proteins encoded by the ras proto oncogenes have not previously been characterized. It is now shown that stimulation of the antigen receptor of T lymphocytes causes a rapid activation of p21ras. The mechanism seems to involve a decrease in the activity of GAP, the GTPase-activating protein, on stimulation of protein kinase C. In lymphocytes, p21ras may therefore be an important mediator of the action of protein kinase C. PMID- 2201922 TI - Suppression of c-ras transformation by GTPase-activating protein. AB - The ras genes are required for normal cell growth and mediate transformation by oncogenes encoding protein tyrosine kinases. Normal ras can transform cells in vitro and in vivo, but mutationally activated ras does so much more efficiently, and highly transforming mutant versions of ras have been isolated from a variety of human and animal tumours. The ras genes encode membrane-associated, guanine nucleotide-binding proteins that are active when GTP is bound and inactive when GDP is bound. The slow intrinsic GTPase activity of normal mammalian Ras proteins can be greatly accelerated by the GTPase-activating protein (GAP), which is predominantly cytoplasmic. This activity of GAP, which can increase with cell density in contact-inhibited cells, suggests that it functions as a negative, upstream regulator of ras. Other studies, however, show that GAP interacts with a region of ras-encoded protein implicated in ras effector function, which raises the possibility that GAP might also be a downstream target of ras. Mutationally activated ras-encoded proteins also interact with GAP, although they are resistant to its catalytic activity. In an attempt to define the role of GAP in ras-mediated transformation, we examined the effects on transformation of normal or mutant ras when cells overexpress GAP. We found that GAP suppresses transformation of NIH 3T3 cells by normal Ha-ras (c-ras) but does not inhibit transformation by activated Ha-ras (v-ras). These results support the hypothesis that GAP functions as a negative regulator of normal ras and make it unlikely that GAP alone is the ras target. PMID- 2201923 TI - Biolistic transformation: microbes to mice. PMID- 2201924 TI - The unreal situation with EPO. "The dream is now a nightmare". PMID- 2201925 TI - Special issue dedicated to Dr. Sidney Udenfriend. PMID- 2201926 TI - Clinical relevance of measuring GABA concentrations in cerebrospinal fluid. AB - Determination of GABA concentrations in human cerebrospinal fluid can be used to assess GABAergic activity in the central nervous system. As CSF free GABA concentrations may vary with age, sex, CSF fraction, and collection and storage conditions, careful attention to these factors are necessary to allow interpretation of results. Longitudinal studies to investigate the influence of pharmacological agents on CSF GABA have proven especially useful to define clinical biochemical activity and have been utilized to attribute the anti epileptic action of vigabatrin, a selective inhibitor of GABA-transaminase, to its effects on brain GABA metabolism. PMID- 2201927 TI - Molecular pharmacology of protein kinases. PMID- 2201929 TI - [Qualitative ultrasound analysis as a preliminary step in revascularization of the femoro-popliteal axis]. AB - The Authors report on the use of non-invasive techniques in the preliminary evaluation of revascularization of the femoral-popliteal axis. The study of this pathology, for which surgery has become less and less frequent, being limited to the more serious cases, has greatly benefited by the use of H/R echography and of Doppler. These techniques, which remain complementary to angiography, have proved very important and reliable for their capacity to visualize the arterial lumen, an important element for the pre- and post surgical evaluation of vascular recanalization and of the relationship of continuity and continuity with the nearby structures. PMID- 2201928 TI - Interphase cytogenetics. PMID- 2201930 TI - [Renal oncocytoma: 2 clinical cases]. AB - Renal oncocytoma is an uncommon benign neoplasm of tubular epithelial origin. It usually occurs as single mass and clinically may be confused with renal cell carcinoma. Angiographic, CT and ultrasound studies may suggest the diagnosis but they are not pathognomonic. The clinical, diagnostic and anatomopathological features of two cases are presented and discussed. PMID- 2201931 TI - [Staplers in surgery: state of the art]. AB - After a review of the technical development and application of staplers from their introduction to the present day, the indications to the use of this instrument in all gastroenterological areas from the oesophagus to the rectum as well as in chest, gynaecological and urological surgery specified. The advantages offered by staplers in the creation of intestinal anastomoses are undeniable, but these instruments must be considered alternatives to traditional surgery, the techniques of which should be well known to all surgeons. In certain areas (gastric, ileal and colonic resections etc.), the now widespread return to single thread manual stitches sheds a new light on staplers and reflects the fact that an anastomosis can be performed just as quickly by hand but will be softer and less rigid than a stapled one. It is only in oesophageal and lower rectal surgery that staplers offer a significant advantage, solving problems where hand suturing cannot. PMID- 2201932 TI - [Diagnostic approach to extra-renal pheochromocytoma]. AB - Stress is laid on certain principles of diagnostic research in the event of extra suprarenal pheochromocytomas. The importance of CT is recalled, specifying the usefulness of complementary examinations such as selective venous catheterism and above all of scintigraphy with 131I MIBG. PMID- 2201933 TI - [Biliary peritonitis caused hy hydatid disease]. AB - After specifying that rupture of a hydatid cyst in the peritoneal cavity is one of the most serious and rarest complications of hepatic hydatidosis, attention is paid to the peritoneal hydatid (o chole-hydatid). The aetiopathogenetic mechanisms and the anatomo-pathological features of this type of lesion are described in brief. Finally, the personally employed diagnostic protocol and therapeutic strategy in the face of this feared complication are reported. PMID- 2201934 TI - [Hepatic abscess. Diagnostic approach and therapeutic orientation]. AB - The paper examines the cases of 7 patients affected by pyogenic liver abscesses who had been brought to the authors' attention over the last 6 years; 2 of whom presented multiple and 5 single abscesses: 4 were located on the right lobe and 1 on the left lobe. The extent of the pathology, its morbidity and mortality necessitate special attention during the diagnostic path in order to discover the origin. CAT and above all ultrasonography have proved to be indispensable tests. The therapeutic approach, which has been compared with previously published data, has eclectically benefited from both antibiotic treatment, used for multiple abscesses, and the insertion of echo-guided drainage, when general conditions do not permit surgical intervention. In the case of liver abscesses whose origin is evident, surgical drainage remains the obligatory choice, whereas, in the authors' opinion, resective surgery is perhaps out of proportion to this type of disease. PMID- 2201935 TI - [Diverticulitis of the right colon. Description of our experience]. AB - Two cases of diverticultis of the right colon are described which received surgical treatment. These lesions often simulate acute appendicitis and thus represent a intraoperative surprise Differential diagnosis using a neoblastic mass is often impossible. The paper stresses the importance of surgical treatment which in general terms is the same as the treatment of the diverticular mass of the left colon. In cases where it is difficult to decide between a phlogostic and neoblastic pathology, it is advised that a right hemicolectomy should be performed in line with criteria for oncological requirements. PMID- 2201936 TI - [Spontaneous rupture of the spleen during infectious mononucleosis]. PMID- 2201937 TI - Maximum intercuspation. A computerized diagnosis. PMID- 2201938 TI - Pennsylvania Medical Society. Membership directory 1990-91. PMID- 2201939 TI - Mask ventilation in congenital central alveolar hypoventilation syndrome. PMID- 2201940 TI - Maternal glucocorticoid therapy and reduced risk of bronchopulmonary dysplasia. AB - Because of substantial clinical and laboratory evidence of the efficacy of glucocorticoids in the treatment of acute pulmonary surfactant deficiency in preterm newborns, we explored the hypothesis that maternal antenatal glucocorticoid receipt is followed by reduced risk of bronchopulmonary dysplasia (BPD). A sample of 223 intubated infants weighing less than 1751 g birth weight provided 76 infants with BPD (defined by both oxygen requirement and compatible chest radiograph) and 147 who had neither BPD characteristic by day 28 of life. When compared to babies who received a complete and timely course of antenatal glucocorticoids, those whose mothers received no glucocorticoids were at prominently increased risk of BPD (odds ratio = 3.0; 95% confidence interval = 1.1, 8.2). Babies whose mothers received a partial course of glucocorticoids were not at increased risk of BPD (odds ratio = 1.3; 95% confidence interval = 0.4, 4.3). Stratification by gender and birth weight at 1 kg showed a benefit of therapy in all strata except that of extremely low birth weight male infants. These data support the hypothesis that maternal antenatal glucocorticoid therapy offers very low birth weight infants protection against BPD. PMID- 2201941 TI - Methylprednisolone therapy for acute asthma in infants and toddlers: a controlled clinical trial. AB - A controlled double-blind trial was carried out to assess the effect of the early introduction of combined corticosteroid and beta-adrenergic drugs for the treatment of acute asthma in infants and toddlers. Seventy-four emergency room patients (aged 7 to 54 months) who were treated for acute asthma were studied. Treatment included, in addition to salbutamol inhalations, a single dose of intramuscular methylprednisolone (4 mg/kg) or normal saline as placebo. The patients were reevaluated 3 hours after initiation of treatment. At that time, patients were either admitted or discharged based on a clinical decision. Only 8 (20%) of 39 patients treated with steroids were admitted, compared with 15 (43%) of 35 in the placebo group (P less than .05). Sequential analysis of 33 pairs, matched by age and severity of symptoms, revealed statistically significant reduced admission rates in patients treated with steroids. In the younger patients (6 to 24 months), admission rate was significantly lower for those treated with steroids (18%) as compared with those treated without steroids (50%) (P less than .05). In the older group (24 to 54 months), the trend was similar but not statistically significant: 23% vs 31% in the steroid and placebo groups, respectively. These data indicate that corticosteroid treatment combined with an adrenergic agent, given early during an acute asthmatic episode, significantly reduces the hospital admission rate of infants and toddlers. PMID- 2201943 TI - [Intraoral ultrasound of the tongue tumor]. AB - Transcutaneous ultrasonography scanned through the submandibular triangle has been effectively utilized for the evaluation of tongue tumors. However, because of lacking an appropriate sonic window, tumors located in the anterior portion of the tongue can not be demonstrated on the transcutaneous ultrasonogram. Intraoral ultrasonography using an echoendoscopy was effective for evaluating neoplasms of the tongue, and could clearly demonstrate tongue tumors, which failed to be shown on the transcutaneous ultrasonograms. In addition, intraoral ultrasonograms could provide more accurate anatomical informations concerning the tumor extent than the transcutaneous ultrasonograms. PMID- 2201942 TI - New colorimetric test for rapid diagnosis of streptococcal pharyngitis: a warning. PMID- 2201944 TI - [CT and US findings of gauzeoma]. AB - We described the CT and US findings of gauzeoma in 7 patients, in which the masses were histologically proved. In the wide range of the CT findings, whirl like spongiform pattern and the wavy striped high density area were characteristic of gauzeomas. The typical US features of gauzeomas were a cystic mass with the distinct internal echoes and strong acoustic shadows. The internal echo were occasionally curve-linear in shape. Gauzeomas are not common disease. However, when the findings described above are seen in the patients who have previously had an abdominal surgery, gauzeomas should be suspected. PMID- 2201945 TI - [Role of CT and ultrasonography in acute blunt trauma of the abdomen]. AB - From March 1985 to April 1989, one hundred thirty-one patients were examined using computed tomography (CT) and/or ultrasonography (US) in the evaluation of acute blunt trauma of the abdomen (CT and US in 36 patients, CT in 25 US in 70). Twenty-three out of the 131 cases (17.6%) showed positive findings of abdominal trauma on CT and/or US. Sixteen of the 23 patients with positive findings underwent therapeutic laparotomy, while all of the other 108 patients with negative findings were successfully managed conservatively. This fact suggests that one of the roles of CT and/or US is to pick up patients with negative findings who do not have any laparotomy. Free fluid collection was demonstrated in all of the 23 patients with positive findings in: all 22 on CT (100%), and 13 of 14 on US (92.9%). In all of the 23 patients but one with an injured mesenterium, injured organ was demonstrated by CT and/or US in: 21 of 22 by CT (95.5%), and 11 of 14 by US (78.6%). In one of the 11 patients, not an immediate US but a follow-up on the next day revealed an injured organ. In 6 out of the 12 patients who underwent both plain and contrast enhancement (CE), CT, CE-CT demonstrated the injured organ more clearly than plain CT. US with sector probe was also useful for demonstrating the injured lesion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2201946 TI - State-approved schools of nursing R.N. 1990. PMID- 2201947 TI - The double role of methyl donor and allosteric effector of S-adenosyl-methionine for Dam methylase of E. coli. AB - The turnover of DNA-adenine-methylase of E. coli strongly decreases when the temperature is lowered. This has allowed us to study the binding of Dam methylase on 14 bp DNA fragments at 0 degrees C by gel retardation in the presence of Ado Met, but without methylation taking place. The enzyme can bind non-specific DNA with low affinity. Binding to the specific sequence occurs in the absence of S adenosyl-methionine (Ado-Met), but is activated by the presence of the methyl donor. The two competitive inhibitors of Ado-Met, sinefungin and S-adenosyl homocysteine, can neither activate this binding to DNA by themselves, nor inhibit this activation by Ado-Met. This suggests that Ado-Met could bind to Dam methylase in two different environments. In one of them, it could play the role of an allosteric effector which would reinforce the affinity of the enzyme for the GATC site. The analogues can not compete for such binding. In the other environment Ado-Met would be in the catalytic site and could be exchanged by its analogues. We have also visualized conformational changes in Dam methylase induced by the simultaneous binding of Ado-Met and the specific target sequence of the enzyme, by an anomaly of migration and partial resistance to proteolytic treatment of the ternary complex Ado-Met/Dam methylase/GATC. PMID- 2201948 TI - Random-breakage mapping, a rapid method for physically locating an internal sequence with respect to the ends of a DNA molecule. AB - We describe a method for determining the position of a cloned internal sequence with respect to the ends of a DNA molecule. The molecules are randomly broken at low frequency and the fragments are subjected to electrophoresis. Southern hybridization using the cloned DNA as a probe identifies only those fragments containing the sequence. The size distribution of these fragments is such that two threshold changes in intensity of signal are seen in the smear pattern below the unbroken molecules. The positions of the changes represent the distances from the sequence to each molecular end. The intensity changes arise because the natural ends of the molecules influence the fragment distribution obtained. From once-broken molecules, no fragments can arise that contain a given sequence and are shorter than the distance between that sequence and the nearest molecular end. We tested the method by using x-rays to induce breakage in yeast DNA. Genes of independently known position were mapped within whole chromosomes or Not I restriction fragments using Southern blots from gels of irradiated molecules. We present equations to predict fragment distribution as a function of break frequency and position of the probed sequence. PMID- 2201950 TI - Nucleotide sequence of the psiA (plasmid SOS inhibition) gene located on the leading region of plasmids F and R6-5. PMID- 2201951 TI - Isolation of two different c-ets-2 proto-oncogenes in Xenopus laevis. PMID- 2201949 TI - On the flexible interaction of yeast factor tau with the bipartite promoter of tRNA genes. AB - Yeast transcription factor tau (analogous to vertebrate TFIIIC) interacts specifically with the internal split promoter of tRNA genes. Binding to the two promoter elements (A block and B block) occurs within 30 seconds even when they are separated by a long intervening sequence. Dimethylsulfate protection analysis of contact points between tau and the noncoding strand of a series of internally deleted tRNA3(Leu) genes shows that the specificity of the interaction is not affected by changes in the distance or in the relative helical orientation of the promoter elements. This result is consistent with the results of previous footprinting experiments (Baker, R.E., Camier, S., Sentenac, A. and Hall, B.D., 1987, Proc. Natl. Acad. Sci. USA, 84, 8768-8772). To test if any physical constraint is imposed on the DNA molecule upon tau binding, we analyzed the effect of introducing random single-strand breaks in the noncoding strand of the tRNA gene. Whereas some nicks located in the A block were found to prevent tau binding, no single-strand break in the B block region or in the DNA between the A and B blocks were observed to inhibit or facilitate the binding of tau. We therefore propose that the great flexibility of the tau-tDNA interaction is mostly due to the tau protein itself. PMID- 2201952 TI - Nucleotide and deduced amino acid sequence of an aspartic proteinase inhibitor homologue from potato tubers (Solanum tuberosum L.). PMID- 2201953 TI - Nucleotide sequence of the rplJL operon and the deduced primary structure of the encoded L10 and L7/L12 proteins of Salmonella typhimurium compared to that of Escherichia coli. PMID- 2201955 TI - Low copy number plasmids for regulated low-level expression of cloned genes in Escherichia coli with blue/white insert screening capability. PMID- 2201954 TI - A novel series of pEX-PINK expression vectors for screening high-level production of (un)fused foreign proteins by rapid visual detection of PINK Escherichia coli clones. PMID- 2201956 TI - An easy method to check the efficiency of biotin end-labelling of DNA-fragments. PMID- 2201957 TI - Remembering the Lady with the Lamp. PMID- 2201958 TI - Florence Nightingale: a pioneer in nursing profession. PMID- 2201959 TI - Oral clindamycin and ciprofloxacin therapy for diabetic foot infections: a retraction. PMID- 2201960 TI - The effect of theophylline on respiratory muscle contractility and fatigue. AB - The traditional role of theophylline as a bronchodilator has been expanded by recent findings that suggest this drug has more than smooth muscle relaxant properties. Several investigators indicate that theophylline has an inotropic effect on respiratory muscle, causing enhanced muscular contraction and prevention of muscle fatigue. In animal studies, the drug enhanced respiratory muscle contraction by 15-20%, with levels in the upper end of the therapeutic range (15-20 mg/L). Results of studies in healthy volunteers and patients with lung disease, however, are conflicting. Five clinical trials demonstrated increased diaphragmatic contractility, whereas seven trials showed no effect, with five referring to the diaphragm and the remaining two to the sternomastoid muscle. Disparity in outcomes may be attributed to differences in patient populations, study designs, and techniques used to determine diaphragmatic contractility. Few long-term trials exist that document significant clinical benefit. Theophylline may prove to be of value in selected populations, such as adults with hypercapnic obstructive lung disease. PMID- 2201961 TI - [Implantology and apprenticeship of an elderly edentulous patient]. PMID- 2201962 TI - [Maxillary support in removable dentures]. PMID- 2201963 TI - Prenatal ultrasonographic diagnosis of radial-ray reduction malformations. AB - Radial-ray reduction malformations (RRRMs) may occur isolated or in association with other anomalies. The data of seven fetuses born with RRRMs were collected. Six fetuses had associated lethal abnormalities of the central nervous system, urogenital system, and/or heart, detected by ultrasound. In five cases, it was possible to establish the precise diagnosis, enabling an informed prognosis and subsequent genetic counselling. The diagnoses were: Edwards syndrome (n = 3), VACTERL association (n = 1), and Poland-Moebius-like complex (n = 1). In two cases, a complete diagnosis was not possible because of inadequate evaluation of these fetuses before and/or after birth. A proposal is given for the diagnostic approach for infants with RRRMs detected in the antenatal period by means of ultrasonography. PMID- 2201964 TI - Prenatal diagnosis and postnatal follow-up of a child with two de novo unrelated balanced reciprocal translocations. AB - Two unrelated, apparently balanced, reciprocal translocations involving chromosomes 3 and 17, and 10 and 15 were found in cultured amniotic fluid cells from a 41-year-old 10-gravida. Chromosome analysis of peripheral blood lymphocytes of both parents revealed normal karyotypes. Post-partum examination of lymphocyte cultures from the proband confirmed the chromosome rearrangements. The child showed normal development during follow-up examinations up to the age of 4 years. PMID- 2201965 TI - [Monoclonal antibodies against Mycobacterium antigens]. PMID- 2201966 TI - [The history of the first All-Russian 3-day campaign against tuberculosis, 1922]. PMID- 2201967 TI - Flutamide blocks the self-priming effect of luteinizing hormone-releasing hormone in pubertal male rats. AB - Castration of pubertal or young adult male rats eliminates the self-priming effect of luteinizing hormone-releasing hormone on luteinizing hormone secretion. Testosterone, dihydrotestosterone, or estradiol will maintain this effect in castrated animals. In order to explore the mechanism by which both dihydrotestosterone and estradiol are capable of maintaining the effect, intact rats as well as castrated animals implanted with testosterone capsules were treated with the antiandrogen Flutamide. In both intact animals and castrated rats bearing testosterone-filled Silastic capsules, Flutamide blocked the self priming effect. These data suggest that the androgen receptor is of primary importance in the maintenance of the self-priming effect. PMID- 2201969 TI - In situ detection of DNA damage in single cells or tissue sections by quantitative immunofluorescence microscopy. PMID- 2201968 TI - Environmental mutagenesis: an assessment of the past twenty years. PMID- 2201970 TI - Recombination and gene conversion: an overview. PMID- 2201971 TI - Molecular mechanism of post-replication repair: formation and resolution of recombination intermediates in vitro. PMID- 2201972 TI - Mechanisms of caffeine inhibition of DNA repair in E. coli. AB - Caffeine inhibits excision repair and photoreactivation in E. coli in vivo. We used purified E. coli enzymes and DNase I footprinting to study the mechanism of inhibition in vitro. Photolyase binds to pyrimidine dimers in DNA in a radiation independent process. Upon irradiation of this enzyme-substrate complex with photoreactivating light, pyrimidine dimers are reverted to their constituent pyrimidine monomers. Using an oligonucleotide containing a thymine dimer at a unique site, we found that caffeine associates with the substrate and inhibits photoreactivation by blocking the binding of photolyase to the dimer. ABC excinuclease catalyses early events of excision repair; recognition of covalently modified DNA and incision of the phosphodiester backbone on both sides of the modification. The UvrA subunit is involved in the damage recognition process, which we studied using an oligonucleotide containing a unique psoralen adduct. UvrA binds to the adduct and protects 33 base pairs surrounding the adduct from DNase I digestion. In the presence of caffeine, the DNaseI footprint of UvrA covers the entire oligonucleotide; thus, caffeine promotes the binding of UvrA to undamaged DNA. UvrA subunits "trapped" by caffeine would be unable to catalyze repair. The intercalators ethidium bromide and chloroquine also promoted UvrA binding to DNA, so it may be caffeine's ability to intercalate into DNA that results in the trapping of UvrA. Thus, as a consequence of its interaction with DNA, caffeine inhibits these repair systems in E. coli by two entirely different mechanisms, by promoting the nonspecific binding of the nucleotide excision repair enzyme and by interfering with specific binding of the photoreactivating enzyme. PMID- 2201973 TI - DNA repair in higher plants. PMID- 2201974 TI - Selective DNA repair in expressed genes in mammalian cells. PMID- 2201975 TI - Evolutionary significance of genetic stability and change. PMID- 2201977 TI - The SUP4-o system for analysis of mutational specificity in yeast. PMID- 2201976 TI - How cells recognize damaged DNA: clues from xeroderma pigmentosum and yeast. AB - Xeroderma pigmentosum (XP) is characterized by the defective excision repair of DNA damaged by many agents, including ultraviolet radiation (UV) and cisplatin. We have identified a factor in human cells that recognizes multiple forms of DNA damage and is absent in XP complementation group E. Denoted XPE binding factor, it is expressed at five-fold higher levels in tumor cell lines resistant to the antitumor drug cisplatin. Finally, although it does not have photoreactivating activity, XPE binding factor shares multiple binding characteristics with yeast photolyase, suggesting that it is the human homolog of photolyase. PMID- 2201978 TI - Z-forming DNA sequences are deletion hot-spots. PMID- 2201980 TI - Chemistry of DNA alkylation and aralkylation. PMID- 2201979 TI - Site specific mutagenesis. PMID- 2201981 TI - DNA adduct formation in relation to tumorigenesis in mice continuously administered 4-aminobiphenyl. PMID- 2201982 TI - Meal-feeding and physical effort. 1. Metabolic changes induced by exercise training. AB - To evaluate the consequences of the combination of meal-feeding (which causes in the long term several adaptations that lead to saving stored energetic substrates), rats subjected to a 2-hr feeding/22-hr fasting schedule were forced to swim 30 min everyday at a fixed hour during four weeks. The results indicate that meal-fed exercised rats: 1) increase food intake above that found in the nonexercising and the corresponding (nonfood-restricted) controls; 2) did not lose weight (in contrast to the controls); 3) initially had a high glycogen mobilization but at the end of the fourth week started to save hepatic glycogen again, despite the intense energy demanding exercise; 4) maintained a slight hyperglycemia; 5) mobilized less free fatty acids than the nonexercising meal-fed rats, probably due to higher insulinemia; 6) had a lower content of ascorbic acid in the adrenal glands in comparison to the control exercising rats; this suggests that the exercise was less stressful in the latter group. PMID- 2201984 TI - Effect of exogenous insulin on meal patterns and stomach emptying in the spiny mouse. AB - Male adult spiny mice (Acomys cahirinus) were acutely challenged with a single dose of regular insulin or saline vehicle SC; either food intake, meal frequency and meal duration, or stomach emptying were then measured. Meal frequency, as well as amount eaten, was significantly higher over a 6-hr period following both 10 and 30 U/kg of insulin than following vehicle injection. Meal duration remained essentially the same across all conditions. When 30 U/kg of insulin was administered either 15 min prior to, or immediately after, a solid food meal, stomach emptying (as measured by dry weight of recovered stomach contents) was accelerated relative to vehicle controls. These data are generally consistent with and extend the comparative literature suggesting a possible link between rate of stomach emptying and insulin-induced hyperphagia in some species. PMID- 2201983 TI - Meal-feeding and physical effort. 2. Metabolic changes induced by an acute exercise. AB - In this study, rats under meal-feeding up to four weeks were submitted to a sudden exercise (swimming) to evaluate the effects of a behavior that requires mobilization of a large amount of energy on some physiological parameters already changed due to the chronic food-restriction. During exercise meal-fed rats: 1) increase the rate of gastric emptying; 2) maintain glycemia more steadily than the controls even during a long-lasting exercise; 3) maintain high liver glycogen concentration and its mobilization starts later on; 4) free fatty acid mobilization is lower than in the controls but during exercise do use much more; 5) keep more glycogen in the muscles (including the heart) than the controls but during the exercise do utilize much more; 6) are slightly less stressful (mainly after a longer exercise) than the controls as suggested by the adrenal ascorbic acid content. PMID- 2201985 TI - Endocrine findings in restrained eaters. AB - Restrained (n = 9) and unrestrained eaters (n = 13) were selected from a group of healthy young women. Blood samples were collected overnight at half-hour intervals. Levels of cortisol, growth hormone, and glucose in both groups did not differ, while restrained eaters had significantly lower insulin values. After a standardized test meal of 500 kcal, restrained eaters had significantly lower norepinephrine values while insulin and glucose values did not differ from those of the unrestrained group. These findings indicate that restrained eating may have a biological basis. PMID- 2201986 TI - Thermal biology of the laboratory rat. AB - The purpose of this paper is to thoroughly review the literature and present a data base of the basic thermoregulatory parameters of the laboratory rat. This review surveys the pertinent papers dealing with various aspects of the thermal biology of the laboratory rat, including: metabolism, thermoneutrality, core and brain temperature, thermal tolerance, thermal conductance and insulation, thermoregulatory effectors (i.e., thermogenesis, peripheral vasomotor tone, evaporation, and behavior), thermal acclimation, growth and reproduction, ontogeny, aging, motor activity and exercise, circadian rhythm and sleep, gender differences, and other parameters. It is shown that many facets of the thermoregulatory system of the laboratory rat are typical to that of most homeothermic species. However, is several instances the rat exhibits unique thermoregulatory responses which are not comparable to other species. PMID- 2201987 TI - [Cyclophosphamide therapy in multiple sclerosis]. PMID- 2201988 TI - A comparison of triiodothyronine and thyroxine in the potentiation of tricyclic antidepressants. AB - Several studies suggest that small amounts of triiodothyronine (T3) will convert tricyclic antidepressant nonresponders into responders within a few days to a few weeks. As thyroxine (T4) is converted to T3 to have its physiological effect, it has been assumed that T4 would have a similar antidepressant effect to that of T3. We carried out a randomized, double-blind evaluation of the antidepressant potentiating effect of T3 as compared with T4. Significantly more patients responded to 3 weeks of T3 as compared with T4 potentiation. Small but significant differential effects of the two thyroid hormones were noted on the Hamilton Rating Scale for Depression. PMID- 2201989 TI - Role of D-1 and D-2 receptor stimulation in sensitization to amphetamine-induced circling behavior and in expression and extinction of the Pavlovian conditioned response. AB - Circling behavior was measured in female rats treated with amphetamine (1.25 mg/kg d-amphetamine sulfate, IP) on 3 consecutive days. On days 4 and 5 saline was substituted for amphetamine. While the amphetamine-induced response was attenuated by both a D-1 (SCH 23390) and a D-2 (metoclopramide) antagonist. sensitization to amphetamine was attenuated by the D-1 antagonist only. In addition, expression of a placebo-like response observed on day 4 (characterized previously as a Pavlovian conditioned response) was attenuated by both the D-1 and D-2 antagonists without disrupting extinction of the response. PMID- 2201990 TI - A matching law analysis of the effects of dopamine receptor antagonists. AB - Herrnstein's matching equation was used to analyze drug effects on performance in random interval reinforcement schedules. Pimozide caused effects compatible with both motor and motivational impairments, in a 5-component multiple schedule, a 3 schedule 3-day cycle (ALT-3), and a 2-schedule 2-day cycle (ALT-2). However, at low doses, both sulpiride and SCH-23390, tested in the ALT-3 and ALT-2 procedures, caused effects compatible with selective motivational impairments. In experiments using the non-multiple schedules, motivational effects increased during the course of the experimental session, under all three drugs. The interpretation of "motor" and "motivational" deficits in the ALT-2 procedure was validated by experiments in which the response-force and deprivation level were systematically varied. The results support the view that dopamine may be involved in the maintenance of rewarded behaviour, but not differentially implicate the D1 or the D2 receptor subtype. PMID- 2201991 TI - Stress and the heart: biobehavioral aspects of sudden cardiac death. AB - Stress has been implicated as a developmental factor in atherosclerotic heart disease, essential hypertension, and sudden cardiac death. This article reviews the mechanisms and biobehavioral effects of stress on the heart, focusing on its relation to sudden cardiac death. Epidemiologic evidence, cultural studies, animal experiments, and human research are reviewed to better understand the biobehavioral aspects of stress on the heart. Emphasis is placed on understanding the interaction of the central nervous system's frontal cortex and hypothalamus with cardiovascular control areas. With today's understanding of the frontal cortex and the interaction of hormones and neurotransmitters with the cardiovascular system, clinical interventions utilizing psychotherapy and psychopharmacology are needed, particularly since both approaches are underutilized in combating arrhythmias. PMID- 2201992 TI - A double-blind, placebo-controlled study of oral acyclovir in postherpetic neuralgia. AB - Twenty-one patients with postherpetic neuralgia of two- to 84-months duration participated in a double-blind, placebo-controlled study of oral acyclovir. Pain perception was assessed with the Melzack Pain Questionnaire at baseline and at two-to six-week intervals during the ensuing six months. Clinically significant pain reduction occurred in eight patients: four received acyclovir, and four received a placebo. Several treatment strategies have been advocated for relief of postherpetic neuralgia. Results of the present study demonstrate the need for a double-blind, placebo-controlled paradigm to substantiate the efficacy of new clinical approaches. The same caveat applies to the more common syndromes encountered in psychiatric practice. PMID- 2201993 TI - Panic disorder associated with permanent pacemaker implantation. PMID- 2201994 TI - DNA hybridization for the diagnosis of microbial disease. PMID- 2201995 TI - Plasmodium falciparum hyperparasitaemia: use of exchange transfusion in seven patients and a review of the literature. AB - During the last 15 years, at least 35 patients with severe falciparum malaria or babesiosis have recovered following treatment by exchange of up to 10 l of blood. In a patient treated in Manchester, a parasitaemia of 2.10 X 10(6) microliters (42 per cent) was virtually eliminated over eight hours by a 3.5 litre exchange blood transfusion. However, the equipment and amounts of compatible blood required for total exchange are rarely available in areas endemic for malaria and the risks of the procedure, including transfusion-related infections, are high. Partial exchange transfusion with one to two litres of blood carried out over two to seven hours, reduced Plasmodium falciparum parasitaemias of 0.33-1.48 X 10(6)/microliters (13-38 per cent) to 0.11-0.81 X 10(6) (4-17 per cent) in six Thai patients who were receiving intravenous quinine. The reduction in parasitaemia ranged from 0.13-0.67 X 10(6) microliters (9-12 per cent) within six hours. During the same period, parasitaemia in 13 patients with cerebral malaria treated with chemotherapy alone showed little reduction from initial levels of 0.20-1.74 X 10(6)/microliters (11-42 per cent). One of the patients who were treated with exchange transfusion died with intractable hypotension before the procedure could be completed and two others developed oliguric renal failure which was controlled by peritoneal dialysis. Partial exchange transfusion is a promising and practical alternative to total exchange where facilities are limited. It deserves further assessment in the rural tropics. PMID- 2201996 TI - Systemic capillary leak syndrome. AB - Systemic capillary leak syndrome is a rare condition characterized by unexplained episodic capillary hyperpermeability. A shift of fluid and protein from the intravascular to the interstitial space results in hypovolaemia. Attacks vary in frequency, severity and duration and can be fatal, although they often remit spontaneously. During acute episodes there is a pathognomonic elevated haematocrit and reduced serum albumin, frequently associated with a monoclonal gammopathy. Treatment has been largely empirical but there are anecdotal reports of beneficial therapy. We describe a further case which highlights the typical clinical presentation, course and investigate findings and review the other cases described. PMID- 2201997 TI - Failla memorial lecture. Time, cells, and X rays. Temporal aspects of some responses of cultured cells to X irradiation. PMID- 2201998 TI - Imaging of the temporomandibular joint. AB - Both arthrography and MR imaging are of proven value in the evaluation of internal derangements of the TMJ. Arthrography provides the advantages of a dynamic display of joint mechanics and the easy detection of disc perforation. Its disadvantages include its technical difficulty and its poor visualization of the disc in the medial-lateral plane. MR imaging of the TMJ provides excellent soft-tissue detail and more readily demonstrates medial and lateral displacements of the disc. Unfortunately, perforations of the disc or ligaments are not usually visualized, and bony detail is not seen as well as on plain radiographs or computed tomography. In addition, real-time dynamic imaging of joint mechanics is not readily available. Currently, the choice of imaging modality is based on the specific diagnostic question, and availability of arthrography and MR imaging. PMID- 2201999 TI - Imaging of the facet joints. AB - Facet joints have a variable anatomic orientation, and their imaging must be adapted to this variation. They have an important role in the stability and mobility of the spine at all levels. They are the sites of microtrauma leading to degenerative changes. Trauma may cause subluxation, dislocation, and fracture. As synovial joints, they manifest inflammatory processes and can present as part of a systemic disease. The facet joints are a component of a trijoint complex at each motion segment and cannot be separated biomechanically. Their visualization and analysis must be integrated with the adjoining soft tissue, and with neural and bone components. PMID- 2202000 TI - Imaging of the sacroiliac joints. AB - The sacroiliac joints present unique problems in diagnosis for both the clinician and the radiologist. Each of the imaging modalities presents advantages and problems. The specific clinical problems determine whether advanced imaging modalities such as scintigraphy, CT scan, or magnetic resonance imaging will complement the information on the plain radiographs. PMID- 2202001 TI - Advanced pediatric joint imaging. AB - Rapid changes are occurring in the field of diagnostic imaging of pediatric joint pathology. CT and ultrasonography have revolutionized imaging, which had previously used only plain film technology. Intravenous sedation administered in the radiology department has facilitated studies that previously were considered impractical or feasible only with general anesthesia. MR imaging shows great promise in replacing certain arthrographic studies, as well as providing important information that has been available only by surgical exploration. Imaging joint disease in the pediatric age group is particularly challenging and at times difficult, but the critical information frequently obtained from these examinations justifies this special effort. PMID- 2202002 TI - Current topics in the radiology of joint replacement surgery. AB - Several methods of total hip joint replacement are currently used. Radiographic appearances after cemented, bone ingrowth, press-fit, and bipolar hip prostheses are reviewed. The roles of nuclear medicine and arthrographic procedures for identifying complications are discussed. Total knee prostheses and, in particular, complications related to the patellar component are described. PMID- 2202003 TI - Imaging of the wrist. AB - A wide variety of radiologic tools now exists for the assessment of the bones and soft tissues of the wrist. The selection of the most appropriate modality requires that the radiologist be conversant both with this armamentarium and with the needs of the referring clinician requesting diagnostic help. Although most static abnormalities may be nicely displayed on routine plain films and special projections, many dynamic abnormalities require motion or stress views to demonstrate their presence. The three-phase radionuclide bone scan allows the radiologist to judge the acute or chronic nature of the abnormality being assessed. Subluxations involving the distal radioulnar joint are relatively easily recognized with CT scanning through that joint. These abnormalities are seen infrequently and are unreliably diagnosed from the plain film examination alone. Although the triple injection arthrogram seems to be a sensitive and accurate tool for identifying ligamentous perforations including those of the triangular fibrocartilage, the potential for those diagnoses to be made with MR imaging is increasingly recognized. PMID- 2202004 TI - Imaging of the elbow. AB - The imaging needs for diagnosis of abnormalities in and about the elbow are presently satisfied in most instances by plain film radiography. Arthrography with tomography and CT has enabled us to delineate the joint space and articular surfaces better. The sensitivity of radionuclide imaging allows early detection of disease processes but lacks specificity. The advantages of MR imaging in the musculoskeletal system should allow improved diagnostic imaging capability about the elbow as it has for other joints. PMID- 2202005 TI - Magnetic resonance imaging of the shoulder. AB - MR imaging has proved to be of great value in the assessment of musculoskeletal imaging. Its superiority in evaluating knee and spine pathology is well established. Recent studies also have established an important role for MR imaging in the assessment of shoulder disorders. Multiplanar capabilities coupled with excellent contrast resolution that allows simultaneous delineation of osseous and soft-tissue structures make MR imaging a useful method for evaluating the complex anatomy of the shoulder. PMID- 2202006 TI - Imaging of hip disorders. AB - Many different imaging modalities are available to assist in the evaluation of hip disease. One must choose the image or series of images that not only provide the most diagnostic and clinical information, but also remain the simplest and most cost effective for the patient. The initial examination should be the conventional radiograph. This will provide, in most instances, the most diagnostic information for arthritic disease, stress and insufficiency fractures, infection, and bone tumors. If the conventional radiograph is normal, or if more information is needed, bone scintigraphy should be done next. Bone scintigraphy will confirm the presence of disease, demonstrate its anatomic location, and give some information as to its physiologic state. Computed tomography does not play an important role in the evaluation of hip disease except in acute fractures involving the acetabulum. MR imaging is the modality of choice for diagnosing and staging osteonecrosis, searching for marrow disease, assessing cartilage abnormality, and evaluating the extent of soft-tissue disease. PMID- 2202007 TI - Imaging of the knee. AB - MR imaging has become the primary imaging modality of the knee. Its advantages include its noninvasive nature, multiplanar imaging capability, excellent soft tissue contrast, and high resolution. The need for multiple imaging modalities is obviated, as the menisci, cruciate ligaments, synovium, articular cartilage, marrow, and periarticular soft tissues can be simultaneously evaluated. Other imaging modalities may occasionally be helpful in the evaluation of specific problems including CT in tibial plateau fractures, real-time ultrasound for the confirmation of a popliteal cyst or popliteal artery aneurysm, and arthrography for the detection of prosthetic joint loosening. PMID- 2202008 TI - Safety considerations in MR imaging. AB - The authors identify eight areas of potential safety concern during clinical magnetic resonance (MR) imaging. These include (a) biologic effects of the static magnetic field; (b) ferromagnetic attractive "projectile" effects of the static magnetic field; (c) potential effects of the relatively slowly time-varying magnetic field gradients; (d) effects of the rapidly varying radio-frequency (RF) magnetic fields, including RF power deposition concerns; (e) auditory considerations from noise caused by the rapidly pulsed magnetic field gradients; (f) safety considerations concerning superconductive systems, including quenches, use of cryogens, and cryogen storage and handling; (g) psychological effects, such as claustrophobia and anxiety induced because of the examination; and (h) possible effects of the intravenous use of the MR contrast agent gadopentetate dimeglumine. The concerns in each of these categories are elaborated upon, and the available data are presented to clarify their status. PMID- 2202009 TI - Clinical radionuclide bone imaging. PMID- 2202010 TI - Renal functional response to dopamine during and after arteriography in patients with chronic renal insufficiency. AB - The potential renal vasodilatory effect of dopamine in improving renal function after arteriography was studied. Sixty patients with preexisting renal insufficiency were prospectively randomized into two groups. Patients in the treated group (n = 30) received an infusion of dopamine for 12 hours starting at the beginning of arteriography. Patients who received placebo infusion with arteriography (n = 30) served as controls. The study was conducted in two different time intervals. In the first interval, serum creatinine levels and 12 hour creatinine clearance values were obtained before and immediately after arteriography in 12 patients in the dopamine group and 13 patients in the control group. In the second interval, the same variables were measured before arteriography and for 3 consecutive days after arteriography in 18 patients in the dopamine group and 17 patients in the control group. Serum creatinine levels became significantly elevated in the control group on the 1st day and remained so on the 3rd day after arteriography, whereas the dopamine group did not show significant elevation of these levels. Creatinine clearance decreased in the control group on the 1st day, but this deterioration was not sustained on the 3rd day. In the dopamine group, there was no deterioration in creatinine clearance on either day, and mean effective renal plasma flow during and after arteriography was greater. PMID- 2202011 TI - The pulsatile portal vein in cases of congestive heart failure: correlation of duplex Doppler findings with right atrial pressures. AB - To better understand portal vein pulsatility in congestive heart failure, the authors compared portal vein spectral patterns to right atrial pressures measured with a Swan-Ganz catheter in 17 adult patients suspected of having congestive heart failure. Portal vein pulsatility was also evaluated in 17 healthy adults. A pulsatility score (scale, 1-5) based on a ratio of minimum to peak portal vein velocity was assigned. A score of 1 indicated continuous, monophasic flow, while a score of 5 indicated that flow reversal was observed with each cardiac cycle. All 17 healthy volunteers had portal vein pulsatility scores of 2 or less. Among the 17 patients suspected of having congestive heart failure, seven had normal right atrial pressure (less than 10 mm Hg) and pulsatility scores of 2 or less. Among the 10 patients with a right atrial pressure of 10 mm Hg or greater, six had pulsatility scores of 3 or greater (sensitivity, 60%; specificity, 100%). Greater than 50% of the variation in portal vein score is explained by changes in right atrial pressure. Review of echocardiograms in 13 of 17 patients showed no significant correlation between the degree of tricuspid regurgitation and portal vein score. Portal vein pulsatility is a sign of elevated systemic venous pressure. PMID- 2202012 TI - Mullerian duct anomalies: MR imaging evaluation. AB - Twenty-nine patients underwent magnetic resonance (MR) imaging for investigation of mullerian duct anomalies (MDAs). The anomalies evaluated were uterine agenesis (n = 2), uterine hypoplasia (n = 5), unicornuate uterus (n = 5), uterus didelphys (n = 5), bicornuate uterus (n = 10), and septate uterus (n = 2). The MR imaging interpretation was correlated with results of laparotomy (n = 18), hysterosalpingography (HSG) (n = 5), laparoscopy (n = 2), hysteroscopy (n = 1), HSG and laparotomy (n = 2), and HSG and laparoscopy (n = 1). MR imaging enabled correct classification of the anomaly in each patient and identification of coincidental gynecologic disease in 10 patients (34%). MR imaging results influenced clinical treatment in six (24%) of 25 patients referred prospectively. Of particular value was the ability to characterize septal tissue (myometrium versus fibrous tissue), identify the patients in whom the septum of bicornuate uteri had both fibrous and myometrial components, and establish that suspected adnexal lesions were actually components of obstructed MDAs. PMID- 2202013 TI - Percutaneous pediatric renal biopsy: use of the biopsy gun. AB - A recently developed biopsy gun was used in the ultrasound (US)-guided biopsy of native kidneys in seven children. The biopsy gun employs a needle (18 gauge) smaller than that usually used for renal biopsies. In all seven cases it provided a core biopsy specimen that contained enough glomeruli to make a definitive histologic diagnosis of renal parenchymal disease. Use of the biopsy gun eliminated the more complicated movements needed to obtain samples with the conventional manual biopsy techniques. No major complications occurred, and in only one case a minor complication, trace hematuria determined by means of dipstick analysis, was found. The time required to obtain the tissue samples was decreased with use of this technique. Because of the advantages of the biopsy gun, the authors now use it exclusively in percutaneous US-guided biopsy of native pediatric kidneys and recommended that this method be considered by other institutions performing similar biopsies. PMID- 2202014 TI - Shoulder impingement syndrome: sonographic evaluation. AB - A method of shoulder sonography in which lateral and anterior elevation of the arm is used during scanning was demonstrated to be effective in cases of suspected impingement syndrome. The value of the method lies in its ability to demonstrate fluid collection in the subacromial-subdeltoid bursal system, with gradual distention of the bursa and lateral pooling of fluid to the subdeltoid portion while the arm is elevated. In 102 of 381 patients studied, surgical diagnosis was available for correlation. Among this group there were seven false negative and three false-positive sonographic findings. A comparison of sonographic with surgical findings demonstrated a sensitivity of 81% and a specificity of 95% in stages I-III, and a sensitivity of 71% and a specificity of 96% in early stages I and II of the impingement syndrome. The results of dynamic shoulder sonographic examination with fluoroscopic radiography provide valuable information in patients with suspected early-stage impingement syndrome. PMID- 2202015 TI - The pump maneuver: an atraumatic adjunct to enhance US needle tip localization. AB - Real-time ultrasound (US)-guided biopsies and drainage procedures require constant visualization of the needle tip. Ensuring optimum needle tip visualization is paramount to the success of these procedures. The authors have found that pumping the stylet in and out of a stationary needle shaft increases the echo-genicity of the needle shaft and tip, thereby facilitating needle localization. This technique, which we have termed "the pump maneuver," is a quick, useful, and atraumatic adjunct to be considered during US-guided percutaneous needle biopsy and drainage procedures. PMID- 2202016 TI - Renal artery stenosis: diagnosis with color duplex US. PMID- 2202018 TI - Development and plasticity of the locus coeruleus: a review of recent physiological and pharmacological experimentation. PMID- 2202017 TI - Emerging concepts of structure-function dynamics in adult brain: the hypothalamo neurohypophysial system. AB - As the first known of the mammalian brain's neuropeptide systems, the magnocellular hypothalamo-neurohypophysial system has become a model. A great deal is known about the stimulus conditions that activate or inactivate the elements of this system, as well as about many of the actions of its peptidergic outputs upon peripheral tissues. The well-characterized actions of two of its products, oxytocin and vasopressin, on mammary, uterine, kidney and vascular tissues have facilitated the integration of newly discovered, often initially puzzling, information into the existing body of knowledge of this important regulatory system. At the same time, new conceptions of the ways in which neuropeptidergic neurons, or groups of neurons, participate in information flow have emerged from studies of the hypothalamo-neurohypophysial system. Early views of the SON and PVN nuclei, the neurons of which make up approximately one-half of this system, did not even associate these interesting, darkly staining anterior hypothalamic cells with hormone secretion from the posterior pituitary. Secretion from this part of the pituitary, it was thought, was neurally evoked from the pituicytes that made the oxytocic and antidiuretic "principles" and then released them upon command. When these views were dispelled by the demonstration that the hormones released from the posterior pituitary were synthesized in the interesting cells of the hypothalamus, the era of mammalian central neural peptidergic systems was born. Progress in developing an ever more complete structural and functional picture of this system has been closely tied to advancements in technology, specifically in the areas of radioimmunoassay, immunocytochemistry, anatomical tracing methods at the light and electron microscopic levels, and sophisticated preparations for electrophysiological investigation. Through the judicious use of these techniques, much has been learned that has led to revision of the earlier held views of this system. In a larger context, much has been learned that is likely to be of general application in understanding the fundamental processes and principles by which the mammalian nervous system works.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2202020 TI - The biological basis of panic: psychological interactions. PMID- 2202019 TI - The role of personality in anxiety disorders. AB - It is widely believed that personality disorders and/or traits (PDT) have significant impact on the phenomenology, severity and consequently the treatment of anxiety disorders (AD). Specific PDT's are thought to be characteristic of certain types of AD's. However, little experimental data support these assumptions. The interpretation of the few comorbidity and outcome studies investigating the role of PDT's in anxiety is problematic from both theoretical and methodological points of view. The authors review what is known about the co occurrence of PDT's and some of the AD's. Particular attention is paid to studies that demonstrate the alteration of PDT's as a result of successful treatment of an AD and to those assessing the difficulties encountered in the treatment of AD's in the presence of certain PDT's. Specific recommendations for much needed research are given. PMID- 2202021 TI - Anxiety and physical illness. AB - Anxiety disorders are more common than previously recognized. Anxiety commonly accompanies a variety of medical disorders and can complicate the treatment of these conditions, leading to increased morbidity and cost. Primary anxiety disorders may actually mimic a variety of medical conditions, with panic patients in particular often going undiagnosed and untreated. Certain medical conditions may present as anxiety so that the unsuspecting physician may inaccurately misattribute a patient's symptoms to a psychiatric rather than a medical condition. PMID- 2202022 TI - Anxiety and the gastrointestinal system. AB - There is a growing recognition that a link exists between anxiety and the gastrointestinal tract. This is evident in studies examining the effects of stress on gastrointestinal function and also in studies assessing psychopathology in patients with functional gastrointestinal disorders which demonstrate a high prevalence of anxiety disorders and depression in these individuals. The recent conceptualization of anxiety as resulting from dysfunction in separable subsystems of the brain as well as experimental evidence linking the brain with the GI tract may allow for testing hypotheses that the high prevalence of anxiety in patients with functional GI disorders may be due to common or interacting pathophysiology. The similarity between the ENS and the CNS may also be a plausible explanation for this association. The high prevalence of anxiety disorders in functional GI patients suggests that medications useful in the treatment of anxiety disorders (anxiolytics and antidepressants) may be useful in the treatment of functional GI disorders especially refractory cases, but further treatment studies are needed. PMID- 2202023 TI - The diagnosis and management of panic disorder. AB - The diagnosis of panic disorder without agoraphobia can very often be quite difficult because of the similarity with physical disorders particularly in the cardiac, gastrointestinal or neurological systems. The distinction must be made between panic attacks appearing as medical problems and medical problems appearing as panic attacks. Sometimes the diagnosis of panic attacks is made only after the medical diagnoses have been excluded. Panic disorder with agoraphobia however is much easier to detect if one carefully traces the historical development of agoraphobia and carefully distinguishes between the anxiety produced by agoraphobia and the panic attacks related to panic disorder. Panic disorder must also be distinguished from other anxiety disorders since the treatment for panic disorder still is quite specific. Once diagnosed however, the treatment of panic disorder without agoraphobia is rather simple. It involves the use of a benzodiazepine, either alprazolam or clonazopam, and perhaps the concomitant use of either imipramine or phenelzine sulfate for the rapid control of anxiety symptoms and continued treatment of the disorder. It is also very helpful to have the patient in psychotherapy either using a supportive or cognitive approach. If the patient has a panic disorder with agoraphobia, the pharmacological approach is the same, with the initiation of treatment using either alprazolam or clonazopam, but the psychotherapeutic approach is somewhat different in that behavioral therapy is emphasized rather than purely supportive or cognitive approaches. Given the fact that 1%-2% of the population is at risk for panic disorder, it is important that the condition be rapidly recognized and treated effectively since the currently available modalities of treatment result in almost total resolution of symptoms. Some individuals will remain on medication for several years while others will find it possible to decrease and/or discontinue their medications after only a few months or a few years. There is little excuse at this point for this disorder to be ineffectively diagnosed or treated. PMID- 2202025 TI - [Sir Robert is no more]. PMID- 2202024 TI - [Does a cone-shaped cannula needle offer an advantage in spinal anesthesia?]. AB - The so-called atraumatic spinal cannula of Sprotte is a modification of the Whitacre spinal needle. It consists of a conical tip with a lateral opening. This cannula (24 G) is said to cause a very low incidence of postspinal headache. In a prospective study, it was compared to a 25 G cannula with a Quincke tip. PATIENTS AND METHOD. The study was carried out on 500 patients who received spinal anesthesia for operations on the lower extremities. The cannulas were randomly assigned to the patients. Puncture characteristics and number of incomplete blocks were evaluated. Postoperatively patients were interviewed on days 1, 3, 5, and 7. Neither the subjects nor the investigator were aware of the type of cannula used. RESULTS. There were no differences with regard to age and sex; 80% of the patients ranged between 15 and 55 years, with a homogeneous spread. Performance of the block was superior with the Sprotte cannula and the incidence of incomplete blocks was lower (1.6% vs 7.8%, P = 0.0011). There was no significant difference with regard to postspinal headache (8.2% vs 7.8%). CONCLUSIONS. The atraumatic cannula had better puncture characteristics, but there was no statistically significant difference with regard to postspinal headaches. PMID- 2202027 TI - Anesthesia and the regulation of breathing. PMID- 2202026 TI - [Spinal anesthesia using a strychnine-stovaine combination in Spain]. AB - Since, in 1898, Augustus Bier developed the injection of anesthetic agents in the intradural space following Corning's technique, there have been many changes in the technique to the present day. One of the most popular was rachi-striene stovainization, which was introduced by Jonnesco and attempted to replace general anesthesia (general rachianesthesia). We describe the original technique, its development and the modifications introduced by two Spanish physicians, Drs. Sagarra and Bartrina. We also discuss its advantages and drawbacks. PMID- 2202028 TI - Are both endogenous and exogenous factors involved in spontaneous foetal abortion? PMID- 2202029 TI - Interruption of murine pregnancy by activation of antigen-non-specific killer cells in the endometrium with indomethacin, high dose IL-2 or a combination. PMID- 2202030 TI - Possible mediators in endotoxin-induced abortion. PMID- 2202031 TI - The role of cytokine cross-talk in preventing abortion. PMID- 2202032 TI - Immunologically mediated abortions: one or several pathways? PMID- 2202033 TI - Are there immune abortions? PMID- 2202034 TI - Immunological factors in human abortion. PMID- 2202035 TI - Visual display terminals and pregnancy outcome--a review of epidemiological studies. PMID- 2202036 TI - [Arteriosclerosis of the lower limbs. Clinical and complementary examinations]. PMID- 2202037 TI - Incidence of regional lymph node metastasis in operable osteogenic sarcoma. AB - Records of 182 consecutive patients with the diagnosis of operable osteogenic sarcoma, treated between 1954 through 1980 by the Breast, Bone and Mixed Tumors Department of the Instituto Nacional de Enfermedades Neoplasicas (Lima, Peru), were reviewed to study the incidence of regional lymph node metastases in this disease. All the patients included in this study had radical surgery, which means the complete resection of the bone where the tumor is located, including the proximal joint, which permitted excision of the regional lymph nodes. Nineteen patients (10.4%) had evidence of sarcoma metastatic to draining lymph nodes. A comprehensive analysis of the literature shows that the incidence of metastasis to the lymph nodes in this study, is higher than those cited in a review of the literature, probably due to the policy in the management of osteogenic sarcoma in our institution, during the period of study. PMID- 2202038 TI - Transrectal ultrasound of the prostate. AB - One hundred and twenty-one transrectal ultrasound examinations of the prostate were performed between August and October of 1987. Indications included screening in 41 patients, evaluation of bladder outlet obstruction in 63 patients, evaluation of palpable nodules in 6 patients, and evaluation after transurethral resection of the prostate in 11 patients. A total of five patients were discovered to have prostate cancer after biopsy of a hypoechoic lesion in a normal feeling prostate by digital rectal examination. One patient was from the screening group, two patients with bladder outlet obstruction and two patients from the postransurethral resection group. All six patients with palpable nodules were diagnosed as having a cancer: Stage B2 on the rectal examination and two of the six patients were upstaged to Stage C by ultrasound criteria. In our hands transrectal ultrasound of the prostate is a valuable adjunct in the urological armamentarium with clear application in the diagnosis and staging of prostate cancer. PMID- 2202039 TI - [Female genital tuberculosis in Tunisia. Apropos of 118 cases at the Rabta Neonatology and Maternity Center in Tunis (January 1984-December 1988)]. AB - The authors have reviewed 118 cases of female genital tuberculosis collected over a 5 year period, from 1st January 1984 up until 31 December 1988, and have compared their results (study group, SG) with those of a similar study (reference group, RG) carried out in the same centre 2 years previously. The following points stand out: the incidence of the disease is stable (6.6 p. cent in the SG versus 5.6 p. cent in the RG); the profile of the woman with genital tuberculosis is that of a young woman of rural origin, generally unvaccinated; sterility is increasingly the predominant motive for consultation (81 p. cent in the SG versus 73 p. cent in the RG); the latent form of genital tuberculosis constitutes 96.4 p. cent of cases in their series versus 93.8 p. cent in the RG; the diagnosis of genital tuberculosis was confirmed histologically in 46 p. cent of cases versus 30 p. cent in the RG, and bacteriologically in 7 p. cent of cases versus 4 p. cent in the RG; medical treatment was initiated for the acute and evolutive forms (35 p. cent of cases). Surgical treatment was indicated for macro-lesional forms which were resistant to medical treatment. PMID- 2202040 TI - [Early prenatal diagnosis of diprosopic syncephalic joined twins]. AB - The authors summarize the case of diprosopic syncephalic joined twins diagnosed at 22 weeks of pregnancy by ultrasonography performed because of hydramnios. The rate of separation anomalies of monozygotic twins is assessed by a review of the literature: from 1 to twenty to fifty thousands for joined twins to 1 per cent fifty thousand to fifteen millions for diprosopus. The etiology is the result of a late division of the egg between D12 and D16. Often an encephalic diprosopic joined twins cause elevated levels of maternal serum alpha protein. Early ultrasonography permits to consider a vaginal therapeutic abortion. PMID- 2202041 TI - [Indications for cesarean section and their outcome at the Hospital Center in Libreville]. AB - Over a 16-year period and 113,739 deliveries, the rate of caesarean sections in the Department of Gynecology-Obstetrics of the Centre Hospitalier of Libreville (Gabon) reaches 1.79 p. cent. Since 1985, there is a highly significant (p less than 0.001) of that rate reaching 2.33 p. cent. A comparative study of two 4-year periods (1981-1984 and 1985-1988) permits to analyze the evolution of caesarean sections. The increase is the result of an improved diagnosis of the pathology during pregnancy, especially pre-eclampsia (6.2 p. cent of indications), a better obstetrical monitoring in pelvic deliveries (7 p. cent) and screening of fetal distress (11 p. cent). The indications remain stable in mechanical dystocias and placenta praevia (40 p. cent) and for scarred uterus (19 p. cent) the rate of which remains at 1 p. cent of the deliveries. The decreased rate of perinatal mortality which has benefited from the improvement of the quality of care is not directly related to the increased rate of caesarean sections: in Africa, caesarean sections are still performed in harmful conditions for saving the mother. Maternal mortality remains high (160 of 100,000 NB) and the mortality of caesarean sections is 9 for 1,000, with only 4 p. 1,000 related to the C. section itself and not to the pathology requiring the procedure. The mortality of caesarean section is 5 times higher than that of vaginal deliveries. Caesarean sections results in uterine ruptures during subsequent pregnancies (2 p. cent of scarred uterus). The increased of caesarean sections may only be considered within the scope of concomitant improvement of prenatal monitoring, obstetrical monitoring and neonatal medicine. PMID- 2202042 TI - [Surgical treatment of stress urinary incontinence in women using a suburethral suspension with a polytetrafluoroethylene sling. Apropos of 95 cases]. AB - Description of a new technique for urethral support which complies with the usual criteria for the efficacy of a surgical cure for stress incontinence without having any of its disadvantages. Presentation of the results, postoperative complications and of the potential role of endovaginal echography in preoperative assessment and follow up. The method can be characterized by: its safety, thanks to the vaginal approach across an operative field the size of a postage stamp, ensuring an uncomplicated postoperative period and a short stay in hospital; its accuracy in suburethral support provided by a strip of expanded polytetrafluoroethylene (Gore-tex soft tissue patch), 30 mm by 10 mm, fixed at the ends to the public insertion of the pubococcygeal tract of the levator muscles, and by its median part to the vesicourethral junction: it is of unrivalled precision, thanks to the peroperative use of an urethrometer which is introduced into the urethra to a certain determined length, either by the application of the formula: urethral length = functional length + 8 mm or, better, from a knowledge of the anatomical length measured between the meatus and the origin of the sphincteral zone during prior endovaginal echography; its efficacy, since the results are stable over time and are obtained without dysuria. These characteristics should make it a first line treatment in the therapeutic arsenal for stress incontinence. PMID- 2202043 TI - [Spontaneous hematoma of the liver in pregnancy: non-surgical treatment. Favorable outcome apropos of a case]. AB - The authors report a case of spontaneous rupture of the liver during pregnancy which occurred in a 31-year old multiparous woman with pre-eclampsia. In the literature, this rare event is associated with both maternal and fetal high mortality rates. Histopathological studies have shown periportal parenchymal lesions, larger sinusoidal fibrin deposits and hemorrhagic infarctions. Our case was successfully managed with termination of pregnancy by cesarean section without surgical procedure toward subcapsular hematoma. Long term follow-up using liver scans is needed. PMID- 2202044 TI - Quantitation of immunoglobulins produced by donor lymphocytes in transplant patients and the possible identification of donor cell-produced antiviral antibodies by imprint immunofixation. AB - In the present study two patients were studied in detail to estimate the quantity of IgG of donor lymphocyte origin. Using IgG subclass quantitation and Gm haemagglutination inhibition titre, we estimated that up to 3% of IgG found after transplantation may be of donor lymphocyte origin. Analysis of viral antibody patterns by imprint immunofixation suggested polyclonal production of donor derived antibodies. PMID- 2202045 TI - Terminally differentiated human intestinal B cells. IgA and IgG subclass producing immunocytes in the distal ileum, including Peyer's patches, compared with lymph nodes and palatine tonsils. AB - The relative distribution of IgA and IgG subclass-producing immunocytes was examined by two-colour immunohistochemistry in normal human distal ileum including Peyer's patches (PP), regional mesenteric lymph nodes (MLN), and peripheral lymph nodes. IgA2 cells predominated slightly over IgA1 cells in the PP dome area. There was a decreasing median proportion of IgA2 cells in the order of PP (52%), distant ileal lamina propria (40%), MLN (32%), and peripheral lymph nodes (11%). The reverse was true for IgA1 cells in independent enumerations. These results support the notion that PP-derived B cells after stimulation are seeded mainly to the lamina propria of the distal gut, but that there is a substantial retention and terminal differentiation of this migrating population in regional MLN. The median subclass proportions of IgG-producing cells in the PP dome area were in independent determinations 68% IgG1, 23% IgG2, 8% IgG3, and 9% IgG4. This distribution was fairly similar to that seen in other tissue categories, except for a trend towards increased IgG1 and reduced IgG2 proportions in peripheral lymph nodes and reduced IgG1 along with increased IgG3 in normal palatine tonsils. The data suggested an association between the expression of IgG2 (and possibly IgG4) and IgA2 in intestinal mucosal immune responses. PMID- 2202046 TI - Immunomorphology of graft-versus-host disease after small bowel transplantation in the rat. AB - The process of graft-versus-host disease (GVHD) elicited by small bowel semi syngeneic grafts in Lewis rats was studied by an immunohistochemical staining technique for analysis of MHC (major histocompatibility complex) class II antigen expression and of T-cell subpopulations in different organs. Specimens from the graft, native bowel, brain, testis, liver, kidney, and skin were taken on days 5, 10, and 15. All the investigated organs displayed strong class II antigen induction during the course of GVHD. In the native bowel of semi-syngeneically transplanted animals, only discrete morphological changes were noted, whereas the graft displayed a generalized serosal reaction with large infiltrates of rounded and polygonal cells expressing class II antigens. This was not observed in the graft of syngeneically transplanted animals. In the lamina propria of the semisyngeneic graft, 'free' lymphocyte-like cells were depleted and, at the same time, localized aggregates of these cells were observed. Crypt cell class II expression in the native bowel, and to some extent in the graft, was increased during GVHD. However, pronounced intraindividual variations in MHC class II antigen expression were noted, and class II expression was therefore not considered to be a good marker for GVHD. PMID- 2202047 TI - [Intravenous congestion anesthesia/-antibiotic administration in cattle- indications,technics, complications]. AB - We present a literature review on current techniques of intravenous regional anesthesia and intravenous regional antibiosis of the distal limb in cattle. Our own experiences performing a combined procedure of intravenous anesthesia and antibiosis (10 million I.U. benzylpenicillin sodium dissolved in 15-20 ml 2% lidocaine hydrochloride) are discussed in detail. Complete anesthesia of the treated limb was achieved in 22 out of 23 cases (96%). The successfully treated animals did not express any symptoms of pain for the entire surgical procedure. In 2 out of 15 patients (13%) we observed serious post-surgical complications. The reason of which was extensive thrombosis of all veins distal of the tourniquet. The age of the clots at the time of slaughtering of the cows was determined histologically. A direct cause effect relationship between intravenous anesthesia/antibiosis and complication is indicated. We conclude that direct toxicity of the 2000-fold overdose of benzylpenicillin (as compared to generally accepted therapeutic levels) most likely caused the problem. We recommend to reduce the dose of penicillin in regional intravenous antibiosis to maximally 100,000 I.U., even in the case of local sepsis. PMID- 2202048 TI - [Ultrasonic diagnosis in dogs and cats. 1. Manner of function, instruments, biological effects]. AB - Ultrasonography utilizes high frequency sound waves between 2 and 10 MHz. Returning echos from reflecting surfaces in the body are displayed as two dimensional images on a CRT screen. Ultrasonography is particularly useful for analysis of internal structures of parenchymal organs such as liver, spleen, kidneys, prostate and uterus, as well as fluid filled organs such as heart, urinary bladder, gallbladder, and pregnant uterus. The clinical examination is safe. Sector transducers with frequencies between 5 and 10 MHz are useful for dogs and cats. PMID- 2202049 TI - Justice Department joins whistle-blower suit. PMID- 2202050 TI - Evidence of changes in protease sensitivity and subunit exchange rate on DNA binding by C/EBP. AB - The transcription factor C/EBP uses a bipartite structural motif to bind DNA. Two protein chains dimerize through a set of amphipathic alpha helices termed the leucine zipper. Highly basic polypeptide regions emerge from the zipper to form a linked set of DNA contact surfaces. In the recently proposed a "scissors grip" model, the paired set of basic regions begin DNA contact at a central point and track in opposite directions along the major groove, forming a molecular clamp around DNA. This model predicts that C/EBP must undertake significant changes in protein conformation as it binds and releases DNA. The basic region of ligand free C/EBP is highly sensitive to protease digestion. Pronounced resistance to proteolysis occurred when C/EBP associated with its specific DNA substrate. Sequencing of discrete proteolytic fragments showed that prominent sites for proteolysis occur at two junction points predicted by the "scissors grip" model. One junction corresponds to the cleft where the basic regions emerge from the leucine zipper. The other corresponds to a localized nonhelical segment that has been hypothesized to contain an N-cap and facilitate the sharp angulation necessary for the basic region to track continuously in the major groove of DNA. PMID- 2202051 TI - Self-concept and cancer in adults: theoretical and methodological issues. AB - Research and theory development on the self-concept have increased dramatically over the last decade. Investigators of the psychosocial aspects of cancer have utilized the self-concept as both an independent and dependent variable. This article discusses quantitative adult studies from the self-concept and cancer literature in terms of their correspondence with current conceptualizations of the self-concept in psychology. The wide gap between recent empirical work and self-concept theorizing is discussed and strategies for future investigations of the self-concept/cancer relationship are outlined. PMID- 2202052 TI - The place of the clock in pediatric advice: rationales, cultural themes, and impediments to breastfeeding. AB - This analysis treats the U.S. medical literature as evidence concerning the formal system of knowledge in allopathic medicine. An examination of pediatric advice on breastfeeding reveals the logic of medical reasoning, the use of scientific rationales, and the intrusion of specific cultural themes. The corpus of data includes works of 18 authors published in 36 volumes from 1897 to 1987, 27 volumes being editions of two major pediatric textbooks. All sources advocate breastfeeding but the detailed advice on how to carry out the process actually tends to undermine it. Moreover, the clock has provided the main frame of reference, creating regimentation reminiscent of factory work, segmenting breastfeeding into a series of steps, and emphasizing efficiency in time and motion. Feeding schedules were advocated in former decades as a matter of discipline for the infant, but nowadays they are viewed as biologically innate to normal infants and to breast milk production. The literature manifests responses over the century to behavioral, biochemical and physiological studies; however, except possibly for one textbook, no thorough rethinking has occurred. Sources of the 1980s continue to focus on the tempo of feeding as a major concern. Cultural themes besides the factory model of breastfeeding include the extension of professional advice to family matters, the subordination of lay women to professional expertise, mistrust of women's bodily signals including the let-down reflex in determining the timing of feedings, mistrust of signals from infants as well, and a professional ideal of flexible advice coupled with rigid limits concerning schedules. The literature interweaves the cultural themes with rationales based on physiological studies in support of specific regimens in breastfeeding, and the relegation of control in breastfeeding to medical experts denies the validity of mutual bodily and emotional responses within the mother infant dyad. Pediatric authorities thus participate in the selection of cultural themes emphasized in motherhood. Although the pediatric literature is not the only influence on physicians and women, it reinforces pressures on women regarding their orientations toward their infants and hence, may be expected to shape our views of infancy, motherhood, and humanity in general. The break from the bindings of schedules has been proclaimed at various points during the century; however, the clock ironically remains the major reference point in most pediatric sources today. PMID- 2202053 TI - [The antitubercular drugs. Overview]. PMID- 2202054 TI - [Imprisonment. Present and historical perspectives]. PMID- 2202055 TI - [Prisons. Birth and history]. PMID- 2202056 TI - [Military medicine during the Second World War, 1941-1945. 45th anniversary of the victory over fascist Germany]. PMID- 2202057 TI - [Organizational and methodological bases of specialization of beds in the home front evacuation hospitals during the Second World War]. PMID- 2202058 TI - [Mechanisms of lesions of myocardial contractility in infectious-allergic myocarditis]. AB - Clinical and morphologic analysis of 63 biopsy specimens and of 23 autopsy specimens has shown the leading role of immune inflammation with the development of delayed and immediate type hypersensitivity in injury to myocardial contractility. It is the immune inflammation that is responsible for disorders in electrolyte metabolism, microcirculation, sympathetic nervous system reactivity. PMID- 2202059 TI - [Ethmozine pharmacokinetics in liver insufficiency]. AB - The authors' findings permit a conclusion that the risk of ethmozine overdosage leading to undesirable side effects (dryness in the mouth, noise in the ears, a 'net' in eyes; giddiness, nausea, vomiting) is very high when routine ethmozine doses are administered to patients with grave (Stages II-III) impairments of liver function; this is explained by (1) reduced rate of ethmozine biotransformation, this resulting in a heightened concentration of the drug in the blood, and (2) by an increase of the drug free fraction concentration due to its reduced ability to bind with the blood plasma proteins. This necessitates a pharmacokinetic monitoring of such patients prescribed ethmozine and a correction of the drug dose, if necessary. PMID- 2202060 TI - [Use of captopril in myocardial infarct]. PMID- 2202061 TI - [Echocardiography: current status and development trends]. PMID- 2202062 TI - [Myasthenia in children and adolescents]. PMID- 2202063 TI - [Captopril in circulatory insufficiency in patients with dilated cardiomyopathy]. PMID- 2202064 TI - [Soviet medicine and physicians in the years of the Second World War]. PMID- 2202066 TI - [High-efficiency hemodialysis. Review of the literature and initial clinical experience]. AB - A literature review allows us to distinguish two types of high efficiency therapy: HED (high efficiency dialysis), with low ultrafiltration coefficient membranes, and HFD (high flux dialysis), with high ultrafiltration coefficient membranes. Data reported show an unchanged hematochemical with the same, or better, treatment tolerance, but there are few data on hydrosaline balance (and correlate hypertension) and middle moleculas removal. Finally we report the experience of our centre in 59 months of treatment in four patients. PMID- 2202065 TI - [Magnetic resonance tomography of joint diseases]. PMID- 2202067 TI - [The intradialytic kinetics of uremic toxins in the diffusion-convection hemodialysis method]. AB - A kinetic evaluation of dialytic methods using a diffusive-convective mechanism in comparison to the standard bicarbonate dialysis was performed in order to verify the possible therapeutic uses. The "kinetic" comparison of PFD and HDF to HBD, using equal quantities of dialysate, showed no significant change in the mention of uremic toxins of small molecular weight and a more efficient capacity to extract beta 2M by the diffusive-convective methods. The biophysical evaluation of dialysis still appears to represent the best means of defining the clearance possibilities and of identifying the most suitable technique for achieving a dialytic adequacy. PMID- 2202068 TI - [Hemodiafiltration: choice or necessity in high-efficiency treatment?]. AB - The risks of back-filtration that occur with the use of high hydraulic permeability membranes with haemodialytic techniques in the course of which the difference between forced and necessary ultrafiltration is compensated for by correcting transmembrane pressure in favour of the dialyser compartment. In this way a form of concealed haemodiafiltration is attained in which the replacement fluid is the dialysing solution, annulling, owing to the possible consequences of the transit of bacterial endotoxins into the circulation, all the advantages linked to the use of these membranes. It is concluded by suggesting the implementation of well controlled haemodiafiltration through the careful quali quantitative evaluation of the replacement fluid. PMID- 2202069 TI - [Role of paired filtration dialysis in substitutive treatment]. AB - The Authors have evaluated the possibilities of use of the PFD in the regular dialysis treatment. At first they have studied in 8 patients the advantages offered by this technique in terms of depuration of small molecules and of tolerance in comparison with HD and HDF. Subsequently, they have compared the performances obtained in HF in a second group of 7 patients with the results observed in PFD executed by using 2 dialyzers on line and, in a second phase, in parallel, extending the comparison parameters to a higher molecular weight solute such as the beta 2-M. The results obtained indicate the PFD as a technique which can offer (compared to HD) a better tolerance and higher depurative performances, which on their turn can eventually allow a reduction of the length of the treatment. Moreover the possibility of executing the PFD with 2 polysulfone dialyzers on line and in parallel, increasing the UF to 13.5 and 15 L, renders this technique competitive with the HF also for its capacity of removing the beta 2-M. PMID- 2202070 TI - [Female infertility. Medically assisted reproduction]. PMID- 2202071 TI - [Nosocomial infections of the respiratory tract]. AB - Nosocomial pneumonia is a well recognized complication in hospitalized patients, particularly in those who are intubated and who receive mechanical ventilation. Pathogenesis, diagnostic approach, treatment as well as prevention are discussed. PMID- 2202072 TI - [Surgical risk in preoperative general infections and/or immune deficiency]. AB - The overall perioperative mortality did not change within the last 30 years. This disappointing reality is influenced by the preoperative physical condition of the increasing number of multimorbid patients. Especially the infectious problem is not to play down and is difficult to objectivize. Preoperative correction of even banal infections and malnutrition can prevent desolate complications. Operation and anesthesia per se raise the infectious danger. PMID- 2202073 TI - [Postoperative wound infection: a preventable complication?]. AB - Postoperative wound sepsis carries high morbidity and additional costs. Its incidence can be reduced by appropriate measures. Continuous infection surveillance is able to reduce the overall infection rate. Besides the basic rules, as care for asepsis, atraumatic surgical technique and careful haemostasis, numerous prophylactic measures are proposed, only part of measures are proposed, only part of them relying on convincing experimental or clinical evidence. Some of these measures are discussed according to the commonly accepted classification of wounds. PMID- 2202074 TI - [Preventive use of antibiotics in surgery: a review]. AB - As a rule, prophylactic antibiotics should only be given pre- or perioperatively as a single shot. Cephalosporins of the first and second generation are still quite effective and appear to be the most widely used drugs for this purpose. In some cases a second drug, like i.e. metronidazole, can be added. For each surgical specialty, the most appropriate prophylactic regimen is discussed. PMID- 2202075 TI - [Intra-abdominal infections]. AB - 50% of the patients admitted for acute abdominal pain have an infectious intra abdominal disease, most of them an appendicitis, a cholecystitis or a diverticulitis. These infectious diseases are due to a noninfectious lesion of the wall of an intestinal organ. The defense mechanism and the bacterial synergism limit the number, nature and local extension of the multiple micro organism, producing a strong selection. For the treatment, antibiotics play an important adjuvant role. The main question in all cases is to determine if the cure of the wall lesion is necessary. Furthermore, it is important to choose the ideal time to do it, according to the extension of the lesion, the immunocompetence and the physiological state of the patient. The advantages and inconveniences of an early or late operation have to be weighted. Some special aspects of appendicitis, cholecystitis and diverticulitis are discussed. PMID- 2202076 TI - [Hematogenous bone and joint infections in children]. AB - Not all children with osteomyelitis or septic arthritis will present with the characteristic findings, i.e. localized pain and swelling, fever and generalized malaise. Diagnostic problems arise in case of the following four special forms or locations of the diseases: neonatal osteomyelitis, because neonates frequently have no signs of infection; osteomyelitis of the spine and septic arthritis of the sacroiliac joint; subacute hematogenous osteomyelitis; chronic osteomyelitis. Acute bone and joint infections are diagnosed clinically. Positive blood cultures are found in only about half of all cases. Cultures of joint fluid or bone cultures are positive in 50 to 90%. The aim of therapy is to avoid destruction of bones or joints or even invalidity. Effective treatment consists of sufficient antibiotics for an adequate period of time and of immobilization. Surgical drainage is mandatory in case of abscess formation in soft tissue, of intramedullary or joint abscess, mainly hip-joint and shoulder, of persistent fever and in all chronic forms of osteomyelitis where areas of sequestra, dead tissue and abscesses may be assumed. PMID- 2202077 TI - [Acute infection following osteosynthesis]. AB - Local infection manifest within 14 days of internal fixation is usually confined to the soft tissues. Indeed it may initially be taken for a wound-healing reaction. Colonization is either primary in open fractures, peroperative during internal fixation, or haematogenous from a remote focus within the injured patient. Successful treatment demands immediate readmission to hospital and energetic management by the rules of septic surgery, if chronic infection is to be avoided. The stability of internal fixation can then often be preserved. PMID- 2202078 TI - [Chronic infection following osteosynthesis]. AB - The chronic infection following internal fixation may develop in a different pattern, according to the risk factor involved. There is no doubt that direct trauma on bone and soft tissue is an important risk factor. The pattern of each infection may differ according to the technique of internal fixation used, i.e. external fixator, plate or intramedullary nailing. The damages are minimized by using the appropriate technique. While bone necrosis in osteomyelitis is present, the pattern of it may be changing. An infected non-union may occur in osteomyelitis (osteitis) when present before bone-healing took place. Should infection overlast the bone-healing period, the localization of the main focus is determinant for the outcome of the infection. The assessment of an osteomyelitis consists in the evaluation of the patient's general aspect and the extension of the infectious disease. Assessing it by plain radiographs, it might be accompanied by leucocyte scanning, CT-scan or MRI. The indication of a more aggressive treatment of chronic osteomyelitis is given in all cases of infected nonunion, chronicle fistulation and in presence of pain and contractures. Antibiotics should only be used in addition to a surgical procedure. PMID- 2202079 TI - [Infected vascular prostheses]. AB - Szilagyi's statement: 'The management of cases with infected arterial implants proves to be a task of grave and sometimes insurmountable difficulty' has kept its validity until today. In spite of restrictive patient selection, perfect surgical skill and perioperative antibiotic prophylaxis, infection of vascular grafts still do occur. Diagnosis has to be established without delay, and treatment of such often fatal infections is an aggressive surgical one. PMID- 2202080 TI - Aminoglycoside-induced ototoxicity. AB - One of the major side effects of aminoglycoside antibiotics (AG) is ototoxicity. The authors review the literature revealing many controversies on every aspect of this side-effect. Although epidemiological studies have to face the problem of reliable evaluation techniques, the incidence of cochleo- and vestibulotoxic side effects has been estimated at 7.5% for each. Netilmicin appears to be less ototoxic. No definite risk factors can be proposed, although age, length of therapy, bacteremia, fever, liver and renal dysfunction are probably very important parameters. Most pathological changes at the cochlear level follow a clear spatial sequence, showing unspecific, degenerative lesions, involving every structure of the cochlea. This makes it impossible to draw etiopathological conclusions. Recent pharmacokinetic studies have rejected the 'accumulation theory' of AGs in perilymph, while also in endolymph no accumulation can be found. Only a few data are available on inner ear tissue levels. Among the different pharmacodynamic hypotheses on the action of AGs, binding of the drug to acidic glycosaminoglycans in the stria vascularis, and interference by the drug with phosphoinositide metabolism in the hair cells seem to be of major importance. PMID- 2202081 TI - Assessment of urinary rat beta 2-microglobulin by enzyme immunoassay. AB - An enzyme immunoassay (EIA) was developed using unlabelled and peroxidase labelled rabbit antibodies to assess urinary rat beta 2-microglobulin (beta 2-m) excretion. It consisted in the adsorption of rabbit anti-rat beta 2-m immunoglobulin to a polystyrene surface, the addition of beta 2-m samples or standard and the addition of peroxidase-labelled rabbit anti-rat beta 2-m immunoglobulin. After addition of hydrogen peroxide and o-phenylenediamine, the enzyme activity of the solid phase was measured photometrically at 490 nm. Analytical recovery of pure beta 2-m in urine was 102%. From determinations made on normal female and male rats, the ranges of 24-h urine beta 2-m individually excreted were found to be 0.84-4.77 and 3.7-17.3 micrograms, respectively. The means +/- SEM were 2.49 +/- 0.17 and 10.2 +/- 0.55 micrograms. EIA was of value in evidencing the tubule-damaging properties of sodium chromate and hexachloro 1,3-butadiene in rats. PMID- 2202082 TI - [An experimental validation of the use of various types of allografts for the replacement of mandibular defects]. AB - The intensity of restructuring of various types of bone transplants and reaction of the adjacent tissues of the femoral distal epiphysis to these transplants was studied in rat experiments. The most manifest bone-inducing properties were detected in demineralized allobone, the least so in formalin-treated one; lyophilized and frozen transplants occupy an intermediate position between these two. These data are recommended to be borne in mind when replacing mandibular defects. PMID- 2202083 TI - [The use of immobilized and native proteolytic enzymes in treating inflammatory periodontal diseases]. AB - .1% solution of native terrilytin, a proteolytic enzyme, and 5% profezyme, an immobilized enzyme, were used in the treatment of periodontal inflammations. To enhance the efficacy of enzyme therapy, the latter agent was combined with an antiseptic and pyrimidine-based methychlozyme paste including 5% of profezyme, 0.2% of chlorohexidine bigluconate, 0.2% of methyluracil, 30% of glycerin, and zinc oxide 74.6%. Use of immobilized and native proteolytic enzymes in therapy of patients with gingivitis and periodontitis permitted reducing the number of sessions 1.5-fold. Multiple-modality treatment was conducive to prolongation of the process remission up to 2 years in 52.31% of patients whereas in conventional therapy such remissions could be achieved in only 20%. PMID- 2202084 TI - [Experience with the use of echolocation in the diagnosis of extraorganic tumors of the neck]. AB - Echolocation was used to diagnose extraorganic [correction of intraorgan] tumors of the neck in 18 patients. The results evidence that echo signals help locate the tumor and its relation to other tissues and organs of the neck, its structure and size, the presence of the capsule or aggressive growth, and locate tumorous nodes beyond the tumor. Echolocation of tumors of the neck is an informative and simple diagnostic method. PMID- 2202085 TI - [The replacement of defects and prevention of dental arch deformities in complete destruction of the crowns in subjects of various ages]. AB - The authors necessitate careful handling of the dental roots and consider it necessary that indications for the use of pin constructions be widened; they suggest original modifications of such designs and analyze the results of treatment of 176 patients. Examinations of 2,664 adolescents have revealed various dentition defects in 23.2 +/- 1.5%, these defects leading to deformations. Orthodontic treatment and prostheses are necessary to prevent these deformations. PMID- 2202087 TI - [The effect of metal dentures in the oral cavity on the electric conductivity of the saliva]. AB - Salivary electric conductivity depends on ion concentration and mobility, on electrochemical and chemical processes related to the presence of dentures made of various alloys in the oral cavity. Therefore, salivary electric conductivity is a significant quantitative characteristic of the processes in the buccal mucosa. PMID- 2202086 TI - [A method for repeat prosthesis in elderly patients with complete loss of the teeth]. AB - Results of repeated prostheses servicing carried out in 30 patients who had completely lost their teeth have demonstrated the efficacy of determining the interalveolar height and the habitual central position of the mandible by swallowing, as well as obtaining of functional impressions by old denture bases under chewing pressure with the mouth closed in elderly patients with oral cavity inconvenient for prosthetics. PMID- 2202088 TI - [Characteristics of the fixation of resin-bonded bridge dentures. Possible errors and measures for their elimination]. AB - Correct choice of the design, thorough fitting of the carcass and its stability on abutment teeth during occlusion and articulation, prosthesis fixation with composite material whose storage time has not expired, strict adherence to the rules recommended by the firm manufacturing the composite are necessary for strong fixation of adhesive dentures. PMID- 2202089 TI - [A comparative analysis of the efficacy of combined treatment in generalized periodontitis of a moderate degree of severity using various splinting designs]. AB - Immediate and late results of periodontitis treatment with the use of various types of joining in 74 patients are analyzed. Traditional casts were employed in 34 cases; in 40 patients fragmentary nonremovable casts with parapulpar fixation were used, as were adhesive one-piece, equatory, and intradental casts. The initial condition of the periodontium was similar in all the patients. Periodontal status was compared over the course of treatment with the use of different casts. Mathematical characteristics were used for analysis: periodontal and gingival indexes; osseous index and hygienic condition index, that were determined before, 30 days, and 12 months after treatment. Only two of the four studied indexes evidenced a reliable improvement of the condition after therapy and joining by traditional techniques, but the effect proved to be unstable, and 12 months after treatment both values significantly grew again. When traditional treatment modalities are used, alleviation of the inflammation and improvement of the hygienic condition of the oral cavity depend not so much on the type of joining but mostly on the initial status of the periodontium. A more manifest and stable reduction of the inflammation and improvement of the oral cavity hygienic status were observed in the patients treated with the use of present-day more physiologic cast designs. This evidence considerable advantages of these new designs vs. the traditional ones. PMID- 2202090 TI - [Classification of criteria characterizing the dynamic process of tooth eruption]. PMID- 2202091 TI - [The protein content and cathepsin D activity of the mandibular bone in rats during fracture healing]. AB - Soluble and total protein content and cathepsin D activity were measured in rat mandibular bone tissue during healing of a fracture treated with proteolytic enzymes (andecalin) or protease inhibitors (contrykal) electrophoresis. Contrykal essentially elevated collagen content in mandibular bone tissue and reduced lysosomal enzymes activity. Andecalin had no noticeable effect on the levels of total protein and collagen, but it significantly increased the activity of cathepsin D. The findings evidence that local contrykal electrophoresis in the focus of injury creates an effective concentration of the drug that enhances the fracture healing and prevents the development of pyoinflammatory complications. PMID- 2202092 TI - Hematologic disorders and ischemic stroke. A selective review. AB - More than a dozen primary hematologic disorders have been associated with ischemic stroke. Inherited deficiencies of antithrombin III, protein C, and protein S have been linked with stroke in case reports; optimal screening requires functional as well as antigenic assays. Antiphospholipid antibodies and lupus anticoagulants are the most frequently identified acquired states associated with ischemic stroke. Polycythemia vera, sickle cell anemia, sickle-C disease, and essential thrombocythemia are the major disorders of formed blood elements causing stroke. Special, step-wise screening for occult prothrombotic entities in stroke patients is recommended for young persons with stroke of uncertain cause, for those with prior venous thrombosis, for those with a family history of unusual thrombosis, and for those with no other explanation for recurrent stroke. Acquired, perhaps transient, abnormalities of platelets, coagulation inhibition, and fibrinolysis may contribute importantly to brain ischemia in synergy with other mechanisms, but at present these remain ill defined. The contribution of prothrombotic diatheses to stroke is probably underrecognized and warrants further investigation. PMID- 2202093 TI - European Stroke Prevention Study. ESPS Group. AB - We compared the outcomes of 2,500 patients who suffered from previous cerebrovascular disorders (transient ischemic attacks, reversible ischemic neurologic deficits, or completed strokes) treated with acetylsalicylic acid plus dipyridamole or matched placebo and followed for 2 years. Treatment was associated with a 33.5% reduction (p less than 0.001) in the incidence of all end points (deaths from all causes or strokes) by intention-to-treat analysis and a 36.5% reduction (p less than 0.001) by explanatory analysis. End point reduction appeared to be similar in men and women. The effect of treatment was similar regardless of the patients' age, nature of the qualifying cerebrovascular event, site of the responsible lesion, and diastolic blood pressure. Our results demonstrate the efficacy of combined therapy, but the efficacy of acetylsalicylic acid or dipyridamole alone and the most effective acetylsalicylic acid dosage remain in question. PMID- 2202094 TI - Role of carotid stenosis in ischemic stroke. AB - Using Doppler ultrasonography, we evaluated the frequency and severity of carotid artery stenosis in 261 patients with carotid ischemic strokes, 813 patients with carotid transient ischemic attacks, 500 patients with asymptomatic neck bruits, and 500 controls. Most patients with strokes and transient ischemic attacks had no associated carotid artery disease (55% and 64%, respectively), and such patients without neck bruits were even more likely to be without carotid artery disease (69% and 77%, respectively). Carotid stenosis was more frequent and more likely to be severe in symptomatic than in asymptomatic patients (p less than 0.0002), even after adjusting for age and sex. Carotid stenosis is present in only a minority of patients with strokes and transient ischemic attacks, especially if neck bruits are absent, and the cause of the ischemic cerebral events in most of these patients remains unexplained. PMID- 2202095 TI - Color-coded Doppler imaging of normal vertebral arteries. AB - Using color-coded Doppler sonography, we studied the vertebral arteries of 42 persons without history or physical signs of vertebrobasilar disease. The intertransverse portion of the vertebral artery was visualized in all persons on both sides. Its origin was visualized in 37 persons (88.1%) on the right side and in 28 (66.7%) on the left; the atlas loop was visualized in 32 persons (76.2%) on the right side and in 36 (85.7%) on the left. Four vertebral arteries were hypoplastic. Peak systolic blood velocity ranged from 19 to 98 (mean 56) cm/sec and peak diastolic blood velocity ranged from 6 to 30 (mean 17) cm/sec. Resistive indices ranged from 0.62 to 0.75 (mean 0.69). Thus, color-coded Doppler sonography seems to be a promising noninvasive method for the evaluation of hemodynamics in the extracranial portion of the vertebral arteries. PMID- 2202096 TI - Stroke in neuroborreliosis. AB - A 20-year-old man suffered two thalamic infarctions during the course of neuroborreliosis and was successfully treated with intravenous ceftriaxone. Review of 11 additional cases of stroke and cerebral vasculitis in neuroborreliosis suggests that there is a meningovascular form of the infection with predilection for the posterior circulation and an association with the European strains of Borrelia burgdorferi. PMID- 2202098 TI - Antibodies to the ring-infected erythrocyte surface antigen and the circumsporozoite protein of Plasmodium falciparum in a rural community from Burkina Faso. AB - A population-based study in Burkina Faso was conducted to determine, under conditions of natural exposure to malaria parasites, the prevalence rate and seasonal variation of antibodies to the repeated amino acid sequences of the Plasmodium falciparum ring-infected erythrocyte antigen (RESA) and the circumsporozoite (CS) protein, and the relationship of the presence of malaria parasites in the blood with the level of these antibodies. A random sample of households was selected and visited twice during 1988, in April just before the rainy season and in September at the end of the rainy season. Serological testing included an immunofluorescent assay for total anti-blood stage antibodies; a modified immunofluorescent assay on glutaraldehyde-fixed parasitized erythrocytes to detect antibodies to RESA; and an enzyme-linked immunosorbent assay (ELISA) using synthetic peptides representing repeat amino acid sequences of RESA [(EENV)5, (EENVEHDA)4, and (DDEHVEEPTVA)2] and CS protein [(PNAN5)]. In April, at the end of the dry season, 98% of the individuals had total P. falciparum antibodies, and 39% had anti-RESA antibodies. 32%, 82%, 80%, and 41% of the individuals had antibodies to the respective peptides. All prevalence rates increased with age. After the rains, in September, prevalence rates and levels of reactivity increased in each serological assay, except in the ELISA with (DDEHVEEPTVA)2. Presence of P. falciparum parasitaemia was inversely related to antibody response to the CS protein (PNAN)5 peptide but not to any other assay. PMID- 2202097 TI - The epidemiology of drug-resistant malaria. PMID- 2202100 TI - Intrinsic individual differences in circumsporozoite antibody response at a hyperendemic malaria focus. AB - Antibody to the repetitive domain of the Plasmodium falciparum circumsporozoite (CS) protein was measured in blood collected over 3 consecutive months from 224 residents of a hyperendemic focus in Thailand. An enzyme-linked immunosorbent assay incorporating the protein ([NANP]15 + NVDP)2 was used. More than 22% of adults produced high antibody titres in all 3 months, even though transmission had stopped. Malaria prevalence in these high-responders was the same as in the rest of the population and the number of consanguineous high-responders was no higher than would be expected by chance. The data suggest that individuals at prolonged, equal risk of malaria inoculation display intrinsic differences in their ability to produce CS antibody. PMID- 2202099 TI - A comparison of two DNA probes, one specific for Plasmodium falciparum and one with wider reactivity, in the diagnosis of malaria. AB - The sensitivity and specificity of 2 probes for the detection of malarial infection was studied. 399 blood samples from Gambian children were tested in a deoxyribonucleic acid (DNA) hybridization assay, and the results compared with the microscopical findings from thick blood films. 8 additional pure Plasmodium malariae and 14 pure P. vivax samples were also assayed. One probe, containing a 21 base pair tandem repeat and highly specific for P. falciparum, detected this species in all except 2 of 74 samples with a parasitaemia of 250 per microliter or more; the overall sensitivity of the probe was 76%. The other probe, a 6 kilobase pair organelle DNA, is conserved in all Plasmodium species so far tested. Its sensitivity for P. falciparum was lower than the 21 base pair repeat, but it detected P. vivax and P. malariae at low levels of parasitaemia, and thus could be useful in field studies. PMID- 2202101 TI - An estimation of the number of malaria sporozoites ejected by a feeding mosquito. AB - Restrained Anopheles stephensi mosquitoes infected with Plasmodium falciparum were made to produce time-dependent series of saliva droplets in mineral oil. The relative volume of each droplet and the number of sporozoites each contained were determined microscopically; gland sporozoites were estimated with an enzyme linked immunosorbent assay. Median gland infection was 8170 and median number of sporozoites ejected was 15 (range, 0-978). Inoculum size was positively correlated to the number of sporozoites in the salivary glands. Most mosquitoes ejected sporozoites only at the beginning of salivation; this suggests that only those parasites in the common and secondary salivary ducts at the time of feeding can be ejected. The small size of inocula may explain some aspects of malaria transmission, including the often observed discrepancy between inoculation and incidence rates. PMID- 2202102 TI - Inhibition of Plasmodium falciparum growth by a synthetic iron chelator. AB - The susceptibility of the chloroquine-resistant malaria parasite Plasmodium falciparum (FCR-3) to a pyridoxal-based iron chelator was tested. 10 microM of the chelator 1[N-ethoxycarbonylmethyl-pyridoxy-lidenium]-2-[2'-pyri dyl] hydrazine bromide (code name L2-9) effectively inhibited growth in vitro of the parasites. Presaturation of the chelator with either ferric or ferrous iron partially blocked the inhibitory effect. Two hours' exposure of parasites to 20 microM L2-9 was sufficient to inhibit their growth irreversibly. Desferrioxamine blocked the inhibitory effect of L2-9. It is suggested that the chelator may be acting by generating free radicals in complexing intracellular iron. PMID- 2202103 TI - Cluster of chloroquine-resistant Plasmodium falciparum malaria cases among short term travellers to Sierra Leone. PMID- 2202104 TI - Sensitivity of Plasmodium falciparum to chlorproguanil in Gambian children after five years of continuous chemoprophylaxis. PMID- 2202106 TI - Factors affecting transmission of Wuchereria bancrofti by anopheline mosquitoes. 3. Uptake and damage to ingested microfilariae by Anopheles gambiae, An. arabiensis, An. merus and An. funestus in east Africa. AB - Laboratory observations were made on the uptake of microfilariae (mf) of Wuchereria bancrofti by Anopheles gambiae, An. arabiensis, An. merus and An. funestus. Over host mf densities ranging from 450/ml to 1735 mf/ml neither the percentage of mosquitoes ingesting mf nor the mean number of mf per mosquito was correlated to host mf density. All mosquito species damaged mf during ingestion but the proportion harmed was independent of host mf density. The mean proportion damaged was 0.67 in An. gambiae, 0.51 in An. merus, 0.47 in An. Arabiensis and 0.26 in An. funestus. A comparison of the mean number of undamaged mf ingested and the number of larvae in the thoracic muscles revealed that not all undamaged mf were able to reach the thoracic muscles. PMID- 2202105 TI - Leishmania infantum MON-98 isolated from dogs in El Agamy, Egypt. PMID- 2202107 TI - Helicobacter (= Campylobacter) pylori in Africa. AB - Epigastric pain is a common complaint throughout Africa, mostly in the form of non-ulcer dyspepsia. It has recently been suggested that Helicobacter (= Campylobacter) pylori, a bacterium that colonizes the gastric mucosa and causes type B gastritis, may be the cause of this epigastric pain. This paper reports the endoscopic, histological and bacteriological findings in 57 patients presenting with epigastric pain to the University of Maiduguri teaching hospital during one year, together with a review of the African literature. Of 57 patients, 49 had non-ulcer dyspepsia, 7 peptic ulceration and 1 carcinoma of the stomach. 93% of the patients had histological gastritis, and of these 87% were colonized with H. pylori. The bacterium was cultured from 13 patients. This high prevalence of gastritis and H. pylori has been found throughout Africa. The figures support a causative role for H. pylori in histological gastritis. At present the evidence in support of a causative role in non-ulcer dyspepsia is not strong enough to be able to recommend the routine use of anti-H. pylori therapy in patients with epigastric pain. PMID- 2202108 TI - Elephantiasis and a curved pew-end in Suffolk, England. PMID- 2202109 TI - Inherited predisposition to cancer. AB - In a minority of cancers, the family history, and sometimes characteristic abnormalities in growth or development of target tissues, suggests strong inherited predisposition. There may also be a much larger number of cases who are less strongly predisposed, with important implications for screening and prevention; because there is usually no family history, however, the recognition and investigation of these cases poses a major problem. PMID- 2202110 TI - Human globin locus activation region (LAR): role in temporal control. AB - A region of DNA located far upstream of the human beta-globin locus is critically involved in the regulation of the beta-globin gene family. Recent experiments in transgenic mice suggest that switching from fetal to adult globin gene expression during human development results from competition among individual globin gene family members for interaction with sequences in this region. The phenotypes of patients with defined hemoglobinopathies support this hypothesis. PMID- 2202111 TI - Discontinuation of one drug in triple drug treatment of renal allograft patients: 1-year results. PMID- 2202112 TI - A controlled trial of azathioprine in combination with cyclosporine in cadaveric renal transplantation. PMID- 2202113 TI - Verapamil prevents posttransplant delayed function and cyclosporine A nephrotoxicity. PMID- 2202114 TI - Morphometric study of renal transplant biopsies using an antibody to brush borders. PMID- 2202115 TI - Duplex ultrasound: monitoring of rejection episodes of renal allografts. PMID- 2202116 TI - Diagnosis of renal transplant artery stenosis by color Doppler ultrasonography. PMID- 2202117 TI - Frequency and clinical influence of lymphoceles after kidney transplantation. PMID- 2202118 TI - Differential effects of peritransplant variables on short- and predicted long term outcome in cyclosporine-treated recipients of cadaveric renal allografts. PMID- 2202119 TI - Results of renal transplantation in diabetic nephropathy. PMID- 2202120 TI - Safety of cyclosporine monotherapy after heart transplantation. PMID- 2202121 TI - Failure of duplex sonography to diagnose hepatic artery thrombosis in a high-risk group of pediatric liver transplant recipients. PMID- 2202122 TI - Recurrence of hepatitis B after liver transplantation: does hepatitis-B immunoglobulin modify the recurrent disease? PMID- 2202123 TI - An immunological comparison of pancreas transplants alone in nonuremic patients versus simultaneous pancreas/kidney transplants in uremic diabetic patients. PMID- 2202124 TI - Exocrine and endocrine function of pancreaticoduodenal grafts versus segmental pancreatic grafts. PMID- 2202125 TI - Advantages of mizoribine over azathioprine in combination therapy with cyclosporine for renal transplantation. PMID- 2202128 TI - Pharmacokinetics and metabolism of cyclosporine A in 19 hemodialysis patients. PMID- 2202129 TI - Comparative study of different methods for measuring blood cyclosporine A levels in kidney transplantation. PMID- 2202127 TI - Requirements for safe prednisone discontinuation in late renal transplantation in recipients immunosuppressed with cyclosporine. PMID- 2202126 TI - Deflazacort versus 6-methylprednisolone in renal transplantation: immunosuppressive activity and side effects. PMID- 2202131 TI - Immunoglobulins in liver allograft rejection: evidence for deposition and secretion within the liver. PMID- 2202130 TI - Class II major histocompatibility complex antigens on cardiac endothelium: an early biopsy marker of rejection in the transplanted human heart. PMID- 2202132 TI - Renal transplantation in highly sensitised recipients. PMID- 2202133 TI - Anti-HLA antibody removal by immunoadsorption. PMID- 2202134 TI - Interleukin 2 receptor in rat allograft rejection. PMID- 2202135 TI - Bioartificial pancreas: islet survival and interleukin-1 action. PMID- 2202136 TI - Prednisolone protects pancreatic B cells against cyclosporine and azathioprine effects. PMID- 2202137 TI - Pancreatic islet isolation with UW solution: a new concept. PMID- 2202138 TI - Complexity of 5-HT pharmacology compounded by electrophysiological data. PMID- 2202139 TI - Cholecystokinin and anxiety. PMID- 2202140 TI - Protein engineering and the study of structure--function relationships in receptors. AB - Protein engineering is a powerful tool for studying relationships between receptor structure and function--providing that it is used and interpreted appropriately. Site-directed mutagenesis, deletion mutagenesis and construction of chimaeric proteins have all been used to characterize receptors. In this review, Walter Ward, David Timms and Alan Fersht describe the application of protein engineering, illustrating important concepts with experimental data. They explain that detailed study of function requires careful dissection of mechanistic steps. Care must also be taken when selecting replacement residues; mutation should not cause delocalized structural reorganization or else the true significance of functional change will remain unclear. PMID- 2202141 TI - The biology and clinical potential of growth factors that regulate myeloid cell production. AB - The colony-stimulating factors are a group of growth factors important in regulating the production of myeloid cells. The past 25 years have seen the identification and characterization of many of these growth factors and, more recently, the molecular cloning of their genes. This has enabled the production of sufficient quantities to assess their biological activity in vivo and in vitro. Some of these recombinant growth factors have also been employed in clinical trials, which have indicated potential uses in the treatment of a variety of diseases. Here, Anthony Whetton considers the biology of haematopoietic growth factors, and the evidence that they may be of value in the treatment of haematopoietic, infectious and malignant disease. PMID- 2202142 TI - [Immediate hypersensitivity]. PMID- 2202143 TI - [Esophageal manometry and gastroesophageal reflux]. PMID- 2202144 TI - [Adenocarcinoma of the duodenum: apropos of a case and review of the literature]. PMID- 2202145 TI - A review of the biochemical roles, toxicity and interactions of zinc, copper and iron: III. Iron. AB - Because of its essentiality, iron occurs in tissues of all living matter especially aerobes. Iron compounds have been utilized in various aspects of argo industry. Iron-binding proteins and their vital role in intestinal uptake, distribution and storage of iron are concisely examined. Ceruloplasmin (cuproenzyme) is imperative for iron mobilization from storage sites for hemoglobin synthesis. There is evidence of relationship between enhance susceptibility to infection and iron deficiency. The extent to which behavioral abnormalities and iron depletion are related remains to be established. The efficacy of chelating agents such as desferroxamine, bicarbonates and ethylene diamine tetraacetic acid (EDTA) against iron overload has been tested. PMID- 2202146 TI - Functions of the auxiliary gene products of the human immunodeficiency virus type 1. PMID- 2202147 TI - The VPg of tobacco etch virus RNA is the 49-kDa proteinase or the N-terminal 24 kDa part of the proteinase. AB - Preparations of tobacco etch virus (TEV) RNA which were purified by sucrose gradient centrifugation, digested with RNase, and analyzed by SDS-polyacrylamide gel electrophoresis contained proteins of 49, 32, and 24 kDa. The 49- and 24-kDa proteins reacted with polyclonal antiserum to the TEV 49-kDa proteinase while the 32-kDa protein reacted with anti-TEV serum. Further purification of the RNA by centrifugation through CsCl removed the coat protein (32 kDa), but not the 49- and 24-kDa proteins. The 49- and 24-kDa proteins did not migrate into a polyacrylamdie gel when the RNA was not digested with RNase. These results indicate that the VPg of TEV is either the 49-kDa proteinase or the 24 kDa that represents the amino-terminal half thereof. PMID- 2202148 TI - Mutants in a conserved region near the carboxy-terminus of HIV-1 Rev identify functionally important residues and exhibit a dominant negative phenotype. AB - The rev protein (Rev) of human immunodeficiency virus increases the cytoplasmic expression of viral structural gene mRNAs. We had previously reported the existence of a region (residues 73-98) near the carboxy-terminus in HIV-1 Rev essential for its function. To further define the structural elements in this region, we examined the effects of substitution mutations in highly conserved residues in this region, between amino acids 75-81, on Rev function. Mutations in Pro76-77 and Arg80 retained Rev function, whereas those in Leu75 and Leu81 abolished Rev activity and exhibited trans-dominant suppression of wt Rev function. The Leu81 mutation, in particular, exhibited an efficient dominant negative phenotype. Leu75 and Leu81 thus appear to define residues essential to the Rev "effector" function. PMID- 2202149 TI - Negative-strand RNA replication by Q beta and MS2 positive-strand RNA phage replicases. AB - Plasmids were constructed which allowed preparation of positive- and negative strand MS2 RNA by in vitro transcription and which expressed the MS2 phage replicase. Transcribed, positive-strand MS2 RNA was infectious to Escherichia coli spheroplasts. Transcribed, negative-strand MS2 RNA was infectious to spheroplasts containing either MS2 replicase or related bacteriophage Q beta replicase. PMID- 2202150 TI - Immunodetection in vivo of beet necrotic yellow vein virus-encoded proteins. AB - Open reading frames identified on the four genomic RNAs of beet necrotic yellow vein virus were cloned into bacterial expression vectors and resulting cl-fusion proteins expressed in Escherichia coli were used to raise polyclonal antibodies. This set of antisera was used to show the presence of 7 of 9 predicted viral proteins in mechanically inoculated Chenopodium quinoa leaves by the Western blot technique. Viral coat protein (p22) and its readthrough protein p85 encoded by RNA-2 could be detected in all subcellular fractions. Two other RNA-2-encoded proteins, p42 and p13, are predominantly associated with membranous structures. Another RNA-2-encoded protein, p14, as well as the two polypeptides p25 and p31, encoded by RNA-3 and -4, respectively, are soluble proteins. The viral proteins could first be detected about the time lesions became visible and increased thereafter except for p85, in which case the amount of the soluble form decreased with time. No protein could be detected corresponding to the RNA-1-encoded p237 protein or to the p15 species encoded by open reading frame V of RNA-2. PMID- 2202151 TI - [Influenza viruses studied by fluorescent immunoassay with temporary resolution]. AB - Monoclonal antibodies, epidemic strains of influenza A and B viruses, conjugates were studied by fluorescence immunoassay with temporary resolution using equipment of different companies. Differences and specificity of monoclonal antibodies to influenza A and B viruses were demonstrated. The highest sensitivity of the method with the test system used was determined, being 20 ng/ml of viral protein. The method was shown to be useful for influenza virus detection both in solutions containing purified virions and in virus-containing allantoic preparations. It was established that virological studies could be carried out using conjugates and knock-down microplates of the national make alongside with foreign ones. PMID- 2202152 TI - [A standard panel of human immunodeficiency virus-positive and -negative blood sera for assessing the sensitivity and specificity of diagnostic immunoenzyme test systems]. AB - The materials on the development of a reference panel of HIV-positive and negative blood sera required for quality control of diagnostic enzyme-immunoassay systems are summarized. Ninety sera (50 HIV-antibody positive and 40 negative) were examined in 2 test systems of national and 3 test systems of foreign companies as well as by immune blotting and immunofluorescence tests. Each serum was characterized by optic density values and antibody titer (for positive sera). The conditions of storage and transportation of serum panels as well as those for control tests were determined. The license and instructions for use for the serum panel have been approved. The serum panel is used in 9 institutions engaged in working out and manufacture of diagnostic test systems. PMID- 2202153 TI - [Stability of the main components of an EIA test system for the serodiagnosis of HIV infection]. AB - The stability of two most important components of the EIA test system for diagnosis of HIV infection, an immunosorbent (HIV antigen adsorbed on polystyrene plates) and antispecies peroxidase conjugate, was studied. The possibility to prolong the shelf life of the test system for at least up to 6 months was demonstrated. At the same time, it is proposed to supplement the existing methods of production control with the conjugate thermostability test developed by the authors who believe that this will allow to exclude conjugates with insufficient stability from the test system kit. PMID- 2202154 TI - [A comparison of the sensitivity of solid-phase immunosorbent methods of diagnosing tick-borne encephalitis]. PMID- 2202156 TI - [The survivability of cells of continuous lines (in suspensions) during transport]. PMID- 2202155 TI - [A test of the use of an immunoenzyme method for demonstrating the tick-borne encephalitis virus in various foci]. PMID- 2202157 TI - Electrocardiographic abnormalities in patients with myotonic dystrophy. AB - In examining the incidence and progression of electrocardiographic abnormalities in 45 patients with myotonic dystrophy, 26 (58%) of whom at entry had at least 1 electrocardiographic abnormality, we found conduction abnormalities in 17 (38%). In 21 patients (47%), new abnormalities developed during follow-up (mean, 4.6 years). The overall incidence of electrocardiographic abnormalities increased to 78%, and the incidence of conduction defects increased to 62%. Second-degree or complete atrioventricular block did not develop in any of the patients. Pseudoinfarction patterns were common at entry and during follow-up and were not correlated with evidence of clinical coronary artery disease. There was no correlation between the presence of electrocardiographic abnormalities and apparent disease severity. PMID- 2202158 TI - The physician as a patient educator. From theory to practice. AB - Patient nonadherence to therapeutic regimens is a serious issue in the practice of medicine. Empiric studies done by professionals from diverse backgrounds have shown that physicians who use educational strategies can be effective in gaining the cooperation of patients to follow their recommendations. The educational model that currently is most familiar to physicians and the one they use most frequently when educating patients is pedagogy, the theoretic basis for teaching children. Andragogy, a theoretic basis for teaching adults, is now being suggested by medical educators as an alternative model. To illustrate the clinical relevance and application of the andragogic approach, studies focusing on physician behaviors associated with behavioral measures of adherence were reviewed, analyzed, and categorized according to a framework called the "ADULT" model. Physicians in a postgraduate training program who have had exposure to this framework and have incorporated it into their practices report less difficulty functioning as patient educators. The systematic use of this approach can have a positive effect on patient adherence. PMID- 2202160 TI - Extracorporeal shock wave lithotripsy of urinary calculi. Theory, efficacy, and adverse effects. AB - Extracorporeal shock wave lithotripsy (ESWL) for the treatment of upper urinary tract stone disease is held in high regard by the public and the profession. Although the efficacy is good (77.4% to 100%) for the treatment of 1- to 2-cm stones in select patients, ESWL may require the assistance of adjuvant procedures in as many as 26% of patients and may need repeating in as many as 32% of patients. These represent more difficult situations in which larger, more numerous, or harder stones may be present and in which ureteral stones are manipulated before treatment. The predominant adverse effect of ESWL treatment is the microvascular disruption of the tissues through which the shock waves pass. In addition, the procedure is painful, with many patients requiring narcotic analgesia. Long-term complications such as the new onset of hypertension have occurred in as many as 8% of treated patients, but much speculation about the long-term effects remains. PMID- 2202162 TI - [Standardized therapy concepts in circumscribed burns. Wishes and reality!]. AB - The vast majority of minor burns requiring treatment are best managed by clear rational concepts of therapy. If these burns are either treated less than optimal or overtreated, complications like infections or delayed wound healing may ensue. In order to draw conclusions from data obtained in studies on patients with minor burns, we need cohort studies making use of clearly defined therapeutic concepts. PMID- 2202159 TI - Pathophysiology and management of endometrial hyperplasia and carcinoma. AB - Endometrial cancer is currently the commonest pelvic malignancy affecting American women, most of whom share the same pathophysiologic basis, that is, unopposed estrogenic stimulation. The initial result of hyperestrogenism is the development of endometrial hyperplasia, which is reversible in most cases by appropriate hormonal therapy. Persistent stimulation eventually leads to atypical hyperplasia with nuclear atypia and invasive carcinoma. Because there is no cost effective screening method for the detection of endometrial hyperplasia and carcinoma, it is essential to survey the high-risk population with appropriate diagnostic techniques. After diagnosis, therapy should be individualized based on pathologic findings (cell type and histologic grade) and extent of disease (International Federation of Gynaecologists and Obstetricians stage, depth of myometrial invasion, and pelvic and para-aortic lymph node status). Recent studies suggest that sex hormone receptors and nuclear DNA ploidy patterns provide useful prognostic information independent of histologic grade. PMID- 2202161 TI - Disseminated Pneumocystis carinii in a patient receiving aerosolized pentamidine prophylaxis. PMID- 2202163 TI - [Topical administration of cyclosporin in psoriasis vulgaris]. AB - Two groups of patients with chronic plaque psoriasis were topically treated either with 10% cyclosporin in a jelly base or with 5% cyclosporin in an ointment base under occlusion. We found that cyclosporin penetrates into the lower epidermis and the dermis, when it is applied under occlusion. Obviously, the target cells are neutrophil granulocytes, since they decrease in number under cyclosporin, whereas the other inflammatory cells as well as the epidermal proliferation remain unchanged. In contrast to systemic application of cyclosporin, we did not observe any clinical differences between plaques treated with cyclosporin and those treated with placebo. PMID- 2202164 TI - [Discoid lupus erythematosus beginning on the eyelids]. AB - We report on a 20-year-old women, who suffered from discoid lupus erythematosus (DLE) beginning on her eyelids with dyschromia and cutaneous infiltration. Similar signs appeared on the top of her nose, her nostrils, and her lower lip. Simultaneously with these alterations, we found a superficial exulceration on her hard palate, which histologically proved typical for DLE. After therapy with chloroquine for 3 weeks, the alterations disappeared. PMID- 2202165 TI - [Status of the problem of spontaneous abortion]. AB - Findings of research into the problem of recurrent spontaneous abortion that has been conducted in major obstetric-gynecological clinics of this country in the recent five-year period are analysed. Risk factors of spontaneous abortion and preterm labour are specified, and the influences of environmental effects, pathogenesis, diagnosis, management, and prognosis are evaluated. Prospects of research in this field are outlined. PMID- 2202166 TI - [The dynamics of the invasive growth of Candida albicans in the host's tissues]. AB - Using experimental models of candidal vaginitis in leukopenic mice and of stomatitis in neonatal animals, who developed the minimal inflammatory response, the author has defined the rate of invasive growth of C. albicans in mucosal stratified epithelium. Pseudomycelium was found to invade the epithelium at an average rate of 2 microns per hour, penetrating the entire epithelial lining within 24-48 hrs. These data have been extrapolated to a clinical condition. On the basis of measurements of mucosal epithelium thickness (carried out with autopsy and biopsy material), presumable periods of the total epithelium penetration were calculated; such penetration results in vascular invasion, thus making possible a disseminated involvement. These periods ranged from 22 to 59 hrs for different mucous membranes. Our findings demonstrate the significance of cellular and tissue defense reactions, which, if suppressed, may induce the fungi, normally found on epithelial surface as saprophytes, invade the host tissues and cause deep (and in some cases disseminated) mycotic involvement within several days. PMID- 2202168 TI - [Clinical forms of atopic neurodermatitis]. AB - Basing on their own observations and analysis of data on the clinical picture and pathogenesis of atopic dermatitis, the authors suggest that four clinical forms of this condition be distinguished: erythematous squamous, erythematous squamous with lichen transformation, lichenoid, and prurigo-like. They consider it advisable that such terms as catarrhal exudative diathesis, childhood eczema, and diffuse neurodermatitis be used no more. Itching is suggested to be considered as a symptom and not cause of itching dermatoses. PMID- 2202167 TI - [The cytoarchitectonics of hard chancre in rabbits with experimental syphilis exposed to soliusul'fon and cefamezine]. AB - Twenty rabbits were infected with Treponema pallidum suspension. Ten animals were injected with solusulfone, the rest with cefamezin. Specific features of syphilis induced by a pool of Treponemas are described, such as T. pallidum ultrastructure, formation of a specific granule, form of the agent aggression. Solusulfone treatment was associated with activation of phagocytosis, that manifested by a shift of the incomplete/complete phagocytosis ratio towards the reaction completion; however, intact T. pallidum were detectable even in 72 hrs after the drug injection. Cefamezin had no effect on the cysts and cyst-like formations at the beginning of the treatment course but these forms of the agent were already undetectable in 48 hours. PMID- 2202169 TI - [The skin manifestations of congenital and acquired hemostatic disorders]. AB - The authors review the literature data on skin symptoms of the most prevalent disorders induced by congenital or acquired defects of blood coagulation. The range of skin changes in hemostasis disorders includes hemorrhages of 5 various types, thromboses, pigmentation disorders, and pustular involvement. Early detection of skin symptoms of hemostasis disorders will improve the diagnosis and timely correction of such conditions. PMID- 2202171 TI - [Therapy of osteomyelitis]. AB - Exogenic post-traumatic bone infection has come strongly into focus of attention, as compared to haematogenic cases. Complex prophylaxis against such infection, therefore, is of great importance. The initial phase of bacterial osteomyelitis must be identified and must be followed by immediate action, as early treatment is absolutely essential. That is why the routes of infection, which depend on the extent of injury and on the mode of primary treatment, as well as all areas affected must be fully detected. Substantial therapeutic steps should include radical sanitation, stabilisation (especially fixateur externe), different variants of drainage, and autogenic spongiosa transplantation. New results have become available also in the context of supplementary specialised antibiotic therapy and coverage of soft tissue. PMID- 2202170 TI - [Etiology, diagnosis and therapy of soft tissue infections]. AB - Soft tissue infections are caused by a multitude of bacteria. Their pathogenicity depends on the ability to adhere to surfaces, certain characteristics of the cell wall, exoenzymes or exotoxins, and endotoxins. Because etiologic classification of soft tissue infections is not satisfactory, we propose a clinical classification. 1. Abscesses are caused by staphylococci (carbuncle or suppurative hydroadenitis) or by polymicrobial infections (most subcutaneous abscesses). They are treated by incision and drainage and primary closure of the skin after drainage and curettage is often successful. Only in special cases are antibiotics indicated. 2. Cellulitis mostly caused by streptococci responds well to antibiotic therapy without surgery. 3. Ulcerative lesions i.e. pseudomonal gangrene and Meleney's gangrene need specific antibiotic therapy and complete excision with delayed grafting. PMID- 2202172 TI - Localization of renin substrate in fetoplacental tissue. AB - Specific polyclonal rabbit anti-human renin substrate-antibodies were used in order to study the distribution of renin substrate immunoreactivity in human fetal and placental tissue. Renin substrate was immunohistochemically detected in human decidua and placenta, as well as in 19 weeks old human fetal liver and kidney. The presence of renin substrate in fetoplacental tissue supports the concept of a locally functioning renin-angiotensin system. PMID- 2202173 TI - The mechanism for the discrepancy between serum total and free thyroxine values induced by autoantibodies: report on two patients with Graves' disease. AB - The sera from two patients with Graves' disease gave abnormally high serum free T4 values as compared with the total T4 and other hormone values, suggesting the presence of autoantibodies to labelled T4 analogue used in the Amersham free T4 assay kit. The autoantibodies appeared to develop after the initiation of methimazole therapy and disappeared again after the cessation of methimazole. This binding activity to labelled T4 analogue was demonstrated to be in the immunoglobulin G with a kappa light chain isotype in both sera, and was displaced by unlabelled T4 in a dose-dependent manner. The binding of immunoglobulin G purified from these sera to labelled T4 or T4 analogue was found to be almost identical to that of the corresponding serum binding. Since the specific radioactivity of labelled T4 analogue used in the Amersham free T4 assay kit is about 10 times higher than that of the labelled T4 in the Amersham total T4 assay kit, serum free T4 determinations are much more vulnerable to thyroid hormone autoantibodies. Thus, in the presence of autoantibodies, a large discrepancy develops between free T4 and total T4 values. PMID- 2202174 TI - Effect of prolonged overnight fasting on energy metabolism in non-insulin dependent diabetic and non-diabetic subjects. AB - The effect on energy metabolism of a 6-h prolongation of the conventional 12-h overnight fast was examined in 9 healthy subjects and in 7 patients with non insulin-dependent diabetes mellitus. Plasma glucose concentration decreased by 7 and 23%, in control and diabetic subjects, respectively. In control subjects, the fall in plasma glucose was associated with a slight but significant fall in plasma insulin and a rise in plasma free fatty acid concentrations. During this same period, the rates of plasma free fatty acid oxidation, measured by infusion of [14C]palmitate, and net lipid oxidation, measured by indirect calorimetry, increased in normal subjects by 55 and 76%, respectively; the rate of glucose oxidation measured by indirect calorimetry decreased by 37%. In the diabetic patients, the free fatty acid oxidation rate was enhanced already after 12 h of fasting compared with controls (2.06 vs 1.30 mumol.kg-1.min-1; p less than 0.05) and did not change significantly during the 6-h observation period. After 18 h of fasting, the rate of plasma free fatty acid oxidation was similar in control and diabetic subjects. The data thus emphasize the need for strict standardization of the overnight fasting period for metabolic studies, and demonstrate the difficulties in comparing basal rates of substrate oxidation between healthy and diabetic subjects. PMID- 2202175 TI - Early changes in thyroid hormone metabolism in the heart, liver, and brown adipose tissue during the induction of low T3 syndrome in streptozotocin-diabetic rats. AB - In order to elucidate the day-by-day development of low T3 syndrome, we made rats diabetic by an injection of streptozotocin. Untreated controls killed at day 0 and rats treated for 8 days with insulin after they had received streptozotocin served as controls. Sub-groups of animals were killed 1, 2, 3, 4 and 8 days after streptozotocin. In serum, heart and liver, T3 was depressed to less than 50% of controls at day 4, whereas the insulin-treated rats differed from controls only as to heart T3. Heart iodothyronine 5'-deiodinase activity was depressed to a minimum at day 3 and depression was not prevented by insulin. Liver iodothyronine 5'-deiodinase activity had not reached a minimum at day 8, and again, insulin treatment did not normalize this parameter. T3 contents and iodothyronine 5' deiodinase activity in brown adipose tissue did not differ from values in controls at any point of time. Thus, in the rats with low T3 syndrome induced by streptozotocin-diabetes, a lowered iodothyronine 5'-deiodinase activity is not fully inhibited by insulin treatment, whereas the T3 content in the liver is re established during an observation period of 8 days. A direct toxic effect of streptozotocin seems unlikely as an in vitro study showed no influence of streptozotocin on iodothyronine 5'-deiodinase activity in the liver. The study thus indicates that iodothyronine 5'-deiodinase activity in the heart and liver is depressed in experimental diabetes, despite near optimal regulation of blood glucose, and we suggest that lowered intracellular T3 production could, after some time, result in a hypothyroid state in different tissues. PMID- 2202176 TI - [TSH receptors in autonomous thyroid adenoma]. PMID- 2202177 TI - Immunopathological findings and thyroid autoantibodies in thyroid autonomy. AB - Different phenomena under consideration, lymphocytic and macrophagic infiltration and increased thyrocyte class I and class II antigen expression, normally ascribed to autoimmune thyroid disease (Graves' disease; Hashimoto's thyroiditis) were frequently found in thyroid glands with autonomous nodules, too. Contrary, nodular formations in the vast majority of nodular goiters were not associated with these immunopathological findings. Furthermore, thyroid microsomal, anti peroxidase and TSH-receptor antibodies although at low frequency rates, were only detected in cases of autonomous nodules but not in cases of nodular goiters. From these findings we conclude that the immune phenomenon observed in thyroid autonomy could not be a consequence of nodular formations but that at least in some cases of thyroid autonomy immunopathogenic mechanisms may play an important role. Based on the fact that class I hyper-expression was more common and that a stronger correlation of cell infiltration with increased class I than with increased class II expression on thyrocytes existed we propose, that if the initial event of the autoimmune process is indeed increased class II expression, this stimulus may more likely originate from increased non-thyrocyte class II positivity (for example dendritic or endothelial cells) than from thyrocyte class II positivity. But, if aberrant class II expression is not the initial stimulus, another candidate could be the increased thyrocyte class I expression observed, probably due to the action of interferon alpha and/or beta induced by any unknown stimulus (viruses?). PMID- 2202178 TI - Autoregulation: effects of iodine. PMID- 2202180 TI - Thyroid infiltrating dendritic cells, epitheloid cells and giant cells in iodine deficiency. AB - This study describes dendritic cells in thyroid sections of iodine deficient goiters. Cells were characterized by monoclonal markers and detected by immunohistochemistry and double labelling immunofluorescence. We observed dendritic cells located in focal aggregates in the interstitium and epitheloid cells as well as multinucleated giant cells filling thyroid follicles. All these cells showed strong positivity for the MHC class II molecules HLA-DR, -DQ, -DP and RFD1, a monoclonal marker for active antigen presenting cells. PMID- 2202179 TI - [Follow-up studies of autonomous adenoma of the thyroid]. PMID- 2202181 TI - [Clinical aspects of thyroid autonomy]. PMID- 2202182 TI - [Diagnosis and therapy of functional thyroid autonomy]. PMID- 2202183 TI - [Sonography of thyroid autonomy]. PMID- 2202185 TI - [Radioiodine therapy of functional autonomy: indications, results, risks]. PMID- 2202184 TI - In-vivo evidence for iodine-induced decrease of thyroid blood flow by color-coded Doppler sonography in normal human thyroid glands. PMID- 2202186 TI - [Pathogenesis of functional autonomy]. PMID- 2202187 TI - Thyroid autoimmunity and thyroid autonomy. AB - While it is well established that autoimmune factors are the cause of goiter and hyperthyroidism in Graves' disease, these factors are not yet considered relevant in the development of thyroid autonomy. While an increased overall frequency of anti-Tg and anti-TPO antibodies has been found in moderate iodine-deficient areas, where thyroid autonomy is more frequently observed, there was evidence indicating that thyroid autoimmune phenomena were the consequence rather than the cause of the goiter. Thyroid Stimulating Antibodies (TSAb) have been reported in sera of patients with nodular autonomous goiter, but their pathogenetic relevance is uncertain, since these findings could not be confirmed by others. In our experience TSAb were detected in few cases with multinodular nontoxic goiter and were always associated with anti-TG and anti TPO antibodies, indicating that these patients have the nodular variant of Graves' disease. Besides TSAb, Thyroid Growth Stimulating Antibodies (TGAb) have been detected by different techniques in several goitrous conditions, including Graves' disease and sporadic or endemic nontoxic goiter. The precise nature of TGAb remains to be clarified, and particularly the relationship between TGAb and TSAb is still a matter of controversy. However, data indicating that TGAb cannot be dissociated from TSAb in Graves' sera suggest that these antibodies can be regarded as a sufficient pathogenetic agent for the development of both goiter and thyroid hyperfunction in Graves' disease. The relevance of TGAb in euthyroid goitrous conditions is uncertain, since conflicting results have been reported.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2202188 TI - Lung fluid balance evaluated by the rate of change of extravascular lung water content. AB - Lung fluid balance was studied in 27 mongrel dogs by measuring changes in extravascular lung water content (EVLW). The expression delta EVLWi, which is the difference in EVLWi per kilo bodyweight per hour between two measurement occasions, was used as an estimate of the rate of change of EVLW. EVLW was measured by a double-indicator dilution technique (EVLWi) using iced glucose and indocyanine green. In addition, EVLW was determined at the end of each experiment with gravimetric technique (EVLWg), which enabled the calculation of a regression equation between EVLWi and EVLWg. Delta EVLWi was calculated repeatedly during an 8-h period of mechanical ventilation (MV) with no application of a positive end expiratory pressure (n = 5), during an 8-h period with a positive end-expiratory pressure (PEEP) of 10 cmH2O (1.0 kPa) (n = 5), during the development of oleic acid (OA)-induced pulmonary oedema (n = 7), and hydrostatic pulmonary oedema (left atrial balloon inflation) (n = 9). An increase of EVLW was seen during PEEP 8 h (mean 35%) and after induction of OA and hydrostatic oedema (mean 300%), but no change was found during MV without PEEP. The regression equation was EVLWi = 5.5 + 0.97 x EVLWg (P = 0.001, r = 0.90). OA-induced oedema caused a mean maximum delta EVLWi of 5.1 ml/kg/h, indicating capillary leakage which, however, was self limiting within 2 h after OA injection. In hydrostatic oedema there was a maximum delta EVLWi of 16.0 ml/kg/h. Delta EVLWi was negative after deflation of the left atrial balloon, indicating reabsorption of oedema. PMID- 2202189 TI - Measurement of dynamic lung fluid balance in the mechanically ventilated dog. Theory and results. AB - An expression (LN) is presented for the net fluid leakage from the intravascular to the extravascular space in the lung. It is based on a new dog model and is the sum of rate of change in extravascular lung water content (EVLW), thoracic lymph flow, and pleural fluid formation. The rate of change of EVLW (delta EVLW) in ml/kg/h was calculated from repeated measurements of EVLW with a double-indicator dilution technique (dye/cold) and corrected according to the relation between EVLW measured by this technique and gravimetry. LN was studied in lung-healthy mechanically ventilated dogs during a prolonged period of mechanical ventilation with and without the application of a positive end-expiratory pressure of 10 cmH2O (1.0 kPa). During mechanical ventilation, LN was found to be 0.3 ml/kg/h in the basal condition, increasing to 0.5 ml/kg/h (P less than 0.01) after a mean period of 7 h. After the application of a positive end-expiratory pressure (PEEP) of 10 cmH2O (1 kPa) for 0.5-2 h, LN was found to increase significantly, from a mean of 0.3 ml/kg/h to 0.9 ml/kg/h (P less than 0.01). We conclude that LN is a useful quantitative expression in experimental studies on lung fluid balance. PMID- 2202190 TI - Randomized comparison of recovery after propofol-nitrous oxide versus thiopentone isoflurane-nitrous oxide anaesthesia in patients undergoing ambulatory surgery. AB - A randomized, prospective study was performed to compare recovery characteristics in 41 ASA physical status I-II patients scheduled for ambulatory surgery with either propofol or thiopentone-isoflurane anaesthesia. Particular attention was focused on the recovery time needed to meet discharge criteria. The propofol group received propofol 2 mg.kg-1 for induction followed by propofol infusion (6 9 mg.kg-1.h-1) 1 min after intubation. The thiopentone-isoflurane group received thiopentone 4 mg.kg-1 for induction followed by isoflurane (0.5-2%) 1 min after endotracheal intubation. Other drugs administered during or after anaesthesia were similar between the groups. The propofol group had significantly (P less than 0.05) faster clinical recovery than the isoflurane group with respect to times to response to commands, eye opening, orientation, ability to stand and void, tolerance to oral fluids, "home-readiness", and recovery of perceptual speed. Patients in the propofol group had significantly less (P less than or equal to 0.05) emesis than the patients given isoflurane. We conclude that in patients undergoing ambulatory surgery propofol infusion is preferable to thiopentone-isoflurane anaesthesia, because it may allow faster discharge home. PMID- 2202191 TI - Axonal swellings in the corticospinal tracts in amyotrophic lateral sclerosis. AB - In 2 of 16 cases with sporadic amyotrophic lateral sclerosis (ALS) large numbers of axonal swellings were observed in the corticospinal tracts over a region extending from the posterior limbs of internal capsules to the bulbar pyramids. On electron microscopy, these axonal swellings were seen to consist of accumulations of neurofilaments and altered neuronal organelles (mitochondria and secondary lysosomes). Their morphology differed from the spheroids seen in the anterior horn in ALS. PMID- 2202192 TI - Cardiac phase-related variability of border detection or densitometric quantitation of postangioplasty lumens. AB - We applied an automated computer program capable of simultaneous geometric (through border detection) and densitometric quantitation of digital angiograms for evaluation of the results of percutaneous transluminal coronary angioplasty (PTCA) in different phases of the same cardiac cycle. Digital subtraction coronary angiograms (DSA) of 28 patients who had undergone PTCA to a total of 30 lesions, were analyzed in diastole, in systole, and in the middle of the cardiac cycle to test the variability in coronary quantitation resulting from random frame selection relative to cardiac phase. Before PTCA there was a low degree of variation between measurements obtained from the same lesion in different phases of the cardiac cycle, in both geometric (coefficient of variation between cardiac phases = 4.2%) and densitometric (coefficient of variation between cardiac phases = 5.1%) quantitation. After PTCA, however, there was a wider variation of values in different cardiac phases, which predominated in the densitometric measurements (coefficient of variation between cardiac phases = 33.6%, compared to 20.6% for geometric measurements). There was less agreement between different post-PTCA phases in densitometry, and discrepancies as large as 47% could occur in densitometric evaluation of the stenotic areas when different phases of the cycle were used. We concluded that border detection or densitometric quantitation of the postangioplasty lumens is subject to greater variation resulting from random frame selection relative to cardiac phase, as compared to preangioplasty assessment. This variation predominates in densitometric quantitation, which seems to be dependent not only on the radiographic projection but also on the cardiac phase. The usefulness of densitometric techniques for the evaluation of PTCA results appears to be questionable. PMID- 2202193 TI - Idiopathic ventricular fibrillation. AB - A review of the literature dealing with sudden death revealed 19 articles in which ostensibly healthy patients with documented VF unrelated to any known cardiac or noncardiac etiology are reported. Fifty-four patients fulfilling the criteria for idiopathic VF, including 14 patients investigated at our institution, are described. The mean age of patients for studies that reported age data was 36 years, with a male-to-female ratio of 2.5 to 1. Over 90% of the patients required resuscitation, while syncope due to nonsustained VF occurred in the rest. Diagnosis of VF was preceded by syncope in one fourth of the patients. Holter monitoring and exercise stress tests were often unrewarding. Available electrophysiologic data revealed a 69% inducibility rate of sustained ventricular tachyarrhythmias using nonaggressive protocols of ventricular stimulation in most cases. Induced tachyarrhythmias were poorly tolerated, and were mostly of polymorphic configuration. Class IA antiarrhythmic agents were highly effective in preventing reinduction of these arrhythmias. Available figures suggest an 11% rate of sudden death within 1 year of diagnosis. Appropriate antiarrhythmic therapy appears to improve prognosis. Reviewed data suggest that idiopathic VF represents an underestimated cause of sudden cardiac death in ostensibly healthy patients. An international registry of patients with idiopathic VF is warranted. PMID- 2202194 TI - Primary endocardial fibroelastosis associated with hydrops fetalis in a premature infant. PMID- 2202195 TI - Congenital absence of the pulmonary valve, intact interventricular septum, and patent ductus arteriosus: management in a newborn infant. PMID- 2202196 TI - Mechanisms of ischemia in coronary artery disease: spontaneous decrease in coronary blood supply. AB - Myocardial ischemia has traditionally been related to increased demand, but recent data suggest that intermittent episodes of decreased supply are also important. This article discusses the phenomena underlying the factors that produce spontaneous (non-effort-related) ischemia. These include local arterial phenomena, arterial plaques, endothelial phenomena, neural phenomena, and circadian patterns. The clinical spectrum of myocardial ischemia can be viewed as an interplay among supply, demand, local arterial reactivity, and acute plaque disruption. In addition, neural phenomena and circadian patterns of multiple cardiovascular phenomena combine to make the coronary circulation susceptible to an increased concentration of events in the morning hours, around the time of awakening. With this extension of our understanding of myocardial ischemia, we have reasonable assurance that methods of treatment will advance significantly in the near future. PMID- 2202197 TI - Management of myocardial ischemia: role of intermittent nitrate therapy. AB - Tolerance to long-term nitrate therapy has now been documented in a large number of clinical studies. These trials have demonstrated attenuation of effect over time but a return of responsiveness with the start of nitrate-free intervals. Intermittent therapy prevents attenuation or tolerance when used as the initial treatment regimen. This strategy is appropriate for use with isosorbide dinitrate, as well as intravenous or transdermal nitroglycerin. Transmucosal nitroglycerin has not been associated with tolerance; the lack of such an effect may be a result of rapid increases and decreases in drug levels. In the future, sulfhydryl donors may also prove useful in prevention or reversal of nitrate tolerance. PMID- 2202198 TI - Retained bile duct stones: T-tube in place, percutaneous or endoscopic management? PMID- 2202199 TI - 5-Aminosalicylic acid suppositories in the maintenance of remission in idiopathic proctitis or proctosigmoiditis: a double-blind placebo-controlled clinical trial. AB - Thirty patients with distal ulcerative colitis in remission (17 proctitis, 13 proctosigmoiditis) were randomly given either 5-aminosalicylic acid (5-ASA) or placebo suppositories, 400 mg bid. During the 1-yr follow-up, patients were assessed clinically every month, and flexible sigmoidoscopy with a rectal pinch biopsy specimen and laboratory data were carried out every 3 months. Two patients in the 5-ASA group chose to withdraw from the study, one relapsed, and 12 remained in remission. In the placebo group, one patient chose to withdraw, 11 relapsed, and three remained in remission. The cumulative remission rate at the 12th month was 92% in the 5-ASA group and 21% in the placebo group. Log rank test showed a significant difference in the relapse rate between the two groups (chi 2 = 14.26, p less than 0.001). No side effects were observed. We conclude that 5 ASA in suppository form (800 mg/day), administered for 1 yr, is safe and effective in maintaining remission of distal ulcerative colitis. PMID- 2202200 TI - Effects of sucralfate and sulglycotide treatment on active gastritis and Helicobacter pylori colonization of the gastric mucosa in non-ulcer dyspepsia patients. AB - We conducted a double-blind randomized treatment study on patients affects by non ulcer dyspepsia in whom multiple biopsy specimens showed active gastritis. Patients were given either 3 g/day of sucralfate (n = 39) or 600 mg/day of sulglycotide (n = 50) for 6 wk, a glycopeptide isolated from pig duodenum constituents. Endoscopy was carried out at baseline and at the end of treatment. We took biopsies from the gastric body (twice) and antrum (six times) at each endoscopy in order to determine grade and extent of gastritis and Helicobacter pylori colonization. Both treatments induced a marked regression of active gastritis (sucralfate group: p less than 0.05 and p less than 0.0001, respectively, in body and in antrum; sulglycotide group: p less than 0.01 and p less than 0.001, respectively). Conversely, Helicobacter pylori colonization remained unchanged at the end of the treatments. At baseline, a close relationship was found between grade of active inflammation in each biopsy and Helicobacter pylori density. After therapy, the association was lost in each treatment group. These results suggest that there can be a remission of active gastritis in patients with non-ulcer dyspepsia even without changes in Helicobacter pylori colonization. This result can be achieved by enhancing the protective properties of the gastric mucosa. PMID- 2202201 TI - Hepatic function and portal hemodynamics in patients with liver cirrhosis. AB - We investigated the distribution of portal blood flow per kilogram of body weight (PBF/BW) in 112 healthy volunteers and 90 patients with liver cirrhosis using an ultrasonic Doppler duplex system. The PBF/BW in healthy volunteers showed a log normal distribution, while the distribution was irregular and showed two peaks in patients with cirrhosis. This irregular distribution was thought to reflect their complex physiopathological state. We next analyzed the relationship between PBF/BW and the data from hepatic function tests (serum albumin, total bilirubin, indocyanine green 15-min retention rate, and indocyanine green plasma disappearance rate) in 48 patients with liver cirrhosis. The patients were divided into four groups according to their portal blood flow: group A with a hepatofugal or stagnant portal blood flow, group B with a hepatopetal PBF/BW of less than 12 ml/min/kg, group C with a hepatopetal PBF/BW of 12 or more but less than 20 ml/min/kg, and group D with a hepatopetal PBF/BW of 20 ml/min/kg or more. Among patients with cirrhosis, group A showed the worst results in hepatic function tests, group D the second worst, and group C the best. The effective hepatic blood flow was thought to have decreased because of the development of extrahepatic portosystemic shunts in the patients in groups A and B, whereas it decreased because of the development of intrahepatic shunts in patients in group D. The results of hepatic function tests deteriorated as a consequence of the decrease in the effective hepatic blood flow. PMID- 2202202 TI - Nonoperative removal of bilateral intrahepatic biliary stones by endoscopic electrohydraulic lithotripsy. AB - We report the successful treatment of bilateral intrahepatic biliary stones by endoscopic electrohydraulic lithotripsy (EHL). EHL is a useful procedure by which large stones can be fragmented easily and complete removal of stones can be attained. PMID- 2202203 TI - Methodological issues in evaluating expanded Medicaid coverage for pregnant women. AB - In a recent effort to lower the US infant mortality rate, Congress has expanded the Medicaid coverage options that states may offer pregnant women. Careful evaluation of changes in perinatal outcome associated with this expanded coverage is needed. The linkage of Medicaid enrollment files of mothers and infants to birth, death, and fetal death certificates is an initial step in assessing the effectiveness that Medicaid coverage expansions have had on pregnancy outcome. Creation of such a database for Tennessee for 1984-1987 revealed that complete information on mother, delivery, and child is available for only three quarters of Medicaid-reimbursed births. Furthermore, Medicaid-reimbursed births that had all three data components had different characteristics and lower mortality rates than did births with missing elements. Those persons seeking to evaluate expanded Medicaid coverage for pregnant women need to be aware that consideration of only those births for whom there is information on mother, delivery, and child may lead to serious underascertainment of fetal, perinatal, and neonatal mortality rates. PMID- 2202204 TI - Sequential intermediate-dose cytosine arabinoside and mitoxantrone for patients with relapsed and refractory acute myelocytic leukemia. AB - Based on in vitro evidence of time-dependent synergistic kill of HL-60 leukemia cells exposed to Ara-C and mitoxantrone, 44 patients with relapsed or refractory AML and 3 with blastic CML were treated with a timed sequence of both drugs. There were 25 females and 22 males, with a median age of 53 (range 21-75). Of 31 patients with relapsed AML, 24 had one prior remission, 6 had two and 1 had three. Of these, 15 had failed a second reinduction attempt. Thirteen patients were primarily refractory to induction with Ara-C plus daunorubicin. Each dose of Ara-C, 500 mg/m2, was followed after 6 hr by mitoxantrone, 5 mg/m2, and the sequence was repeated four to six times (44-68 hr) in different cohorts of patients. All but two patients (one with blastic CML and one in relapse and refractory) are evaluable for response and toxicity. Of 16 patients in relapse without prior reinduction 7 achieved CR and 3 PR (62% response rate); there were 3 CR in the 14 patients who were in relapse and refractory (21% response rate) and 4 CR and 1 PR (35% response rate) in the 14 patients with primary anthracycline resistance. Five of seven patients previously exposed to mitoxantrone achieved CR. Response lasted from 2 to 42 months, with two patients alive and in continuing remission at 34 and 42 months. Average marrow recovery was seen after 25 days and time to remission was 30 days. Six patients died in induction (four from sepsis and two from the tumor lysis syndrome) and 21 had progressive disease. Chemotherapy was well tolerated with minor nausea and vomiting in 13 patients, moderate in 20, and severe in 2. Most patients did not have evidence of drug-induced mucositis: it was minor in 9 and moderate in 2. Renal dysfunction was attributable to the use of nephrotoxic antibiotics. Hepatic dysfunction was reversible and was minor in 10 patients, moderate in 13, and severe in 3. Sequential, timed administration of intermediate-dose Ara-C and mitoxantrone is an active and well-tolerated antileukemic regimen. PMID- 2202205 TI - Richter syndrome with two B cell clones possessing different surface immunoglobulins and immunoglobulin gene rearrangements. AB - A patient with two populations of B cell malignancy in the bone marrow is reported. One population consisted of mature small lymphocytes, expressing surface IgM + D, lambda and proliferating very slowly. The other population consisted of abnormal large lymphoid cells, expressing surface IgM, K and proliferating actively. We considered the former as chronic lymphocytic leukemia cells and the latter as malignant lymphoma cells. Therefore, this case was considered as Richter syndrome. The analysis of immunoglobulin heavy chain gene rearrangement showed the different patterns between the two populations. It suggested that the two populations arose from the different origins. We discussed the genetic relationship between the two clones of Richter syndrome referring to other reported cases. PMID- 2202206 TI - Hemostasis in malignancy. AB - Hemostatic abnormalities are present in a majority of patients with metastatic cancer. These abnormalities can be categorized as 1) increased platelet aggregation and activation, 2) abnormal activation of coagulation cascade, 3) release of plasminogen activator, and 4) decreased hepatic synthesis of anticoagulant proteins like Protein C and antithrombin III. The abnormal activation of coagulation cascade is mediated through release of Tissue Factor, Factor X activators, and other miscellaneous procoagulants from the plasma membrane vesicles of tumor cells. Macrophages of a tumor-bearing host also produce increased amounts of Tissue Factor. Production of Factor X activators and macrophage Tissue Factor is decreased by warfarin. The ability of the tumor cells to produce platelet-aggregating activity and plasminogen activator parallels their metastatic potential in animal and experimental systems. These studies also show that antiplatelet agents and antibodies against plasminogen activator can suppress the metastatic process. One or more laboratory abnormalities of hemostasis can be shown in up to 95% of patients with metastatic cancer. These abnormalities, however, are unable to predict subsequent development of thromboembolic or hemorrhagic complications. Clinical complications occur in 9 15% of the patients in the form of thrombotic or hemorrhagic disorders. The therapy of tumor-related coagulopathy should be guided by its clinical expression. Subclinical DIC should not be treated. Coumadin is generally ineffective for therapy of thrombosis in cancer patients. There is no consensus regarding the use of heparin in acute promyelocytic leukemia (APL). The defibrination in APL may be from disseminated intravascular coagulation as well as systemic fibrinolysis, as shown by decreased alpha 2 antiplasmin levels. In such cases, epsilon aminocaproic acid plus heparin therapy may be of benefit. PMID- 2202207 TI - Stability of captopril in powder papers under three storage conditions. AB - The stability of captopril in powder papers under three different storage conditions was determined. Captopril 12.5-mg tablets were triturated with lactose to a final concentration of 2 mg of captopril in 100 mg of powder. A total of 240 powder papers were prepared and stored in class "A" prescription vials (80 papers), 002G plastic zip-lock bags (80 papers), and Moisture Proof Barrier Bags (80 papers). Immediately after preparation and at 1, 2, 3, 4, 8, 12, and 24 weeks of storage at room temperature, powder papers under each storage condition were reweighed and the contents were assayed for captopril concentration by a stability-indicating high-performance liquid chromatographic method. More than 90% of the initial captopril concentration was retained under all storage conditions during the first 12 weeks of the study. Captopril disulfide, a degradation product, was detected in one sample stored in a plastic zip-lock bag at 24 weeks. Captopril was stable for the entire 24-week period in powder papers stored in either the class A prescription vial or the Moisture Proof Barrier Bag. Captopril in powder papers is stable for at least 12 weeks when stored at room temperature under all three storage conditions. PMID- 2202208 TI - Pain management with spinally administered opioids. AB - The use of spinally administered opioids to manage pain is discussed. Central action on opioid receptors of the substantia gelatinosa allows opioids to be administered spinally for pain originating anywhere inferior to the cranial nerves. Spinal opioids are most commonly administered for intractable midline sacral and perineal pain. The best candidates for spinal opioids are patients in whom appropriate "conventional" therapy no longer provides adequate relief, patients who experience severe adverse effects from conventional therapy, and patients for whom alternative anesthetic procedures are inappropriate or have failed. A reasonably safe initial dose is morphine sulfate 1 mg intrathecally. The availability of preservative-free, concentrated morphine sulfate enables larger doses to be safely and comfortably administered. Increased dosage requirements may result from tolerance, progression of disease, increased systemic absorption, or slippage of the catheter tip. As with systemically administered opioids, care must be exercised when discontinuing spinal opioid therapy. Adjuvant drugs used with spinal opioids include systemically administered analgesics, antidepressants, corticosteroids, and spinal local anesthetics. The administration of spinal opioids with systemic opioids or other CNS depressants may result in excessive sedation, respiratory depression, nausea, vomiting, constipation, pruritus, and other adverse effects. Spinally administered opioids can be used to manage severe chronic pain effectively, safely, and comfortably. PMID- 2202210 TI - Understanding cancer pain. AB - The pathogenesis of cancer pain, the incidence of pain associated with specific types of malignant tumors, and the nature of acute and chronic pain are discussed, and alternative delivery systems for pain management are described. More than 80% of cancer patients with advanced metastatic disease suffer moderate to severe pain. Most cancer pain is caused by direct tumor infiltration; approximately 20% of cancer pain may be attributed to the effects of surgery, radio-therapy, or chemotherapy. The incidence of cancer pain is related to tumor type; 70% or more of patients with tumors of the bone, cervix, and ovaries suffer cancer-related pain, while only 5% of patients with leukemia have pain. Pain is defined by the organs involved. Somatic pain is usually dull and well localized; visceral pain is generalized and difficult to describe. Other types of pain, including deafferentation pain and referred pain, are particularly difficult to manage. Cancer pain may be acute or chronic. The latter may cause psychological reactions that make effective treatment more challenging. Opiate analgesic agents, administered by the epidural or intrathecal routes, block pain more selectively and produce fewer adverse reactions than systemic analgesic agents. The duration and onset of analgesia depend on the lipophilicity of the agent used. Because pain is the most common complaint of the patient with cancer, clinicians should be aware of the range of pharmacologic and nonpharmacologic analgesic modalities available to them. Familiarity with newer modalities and delivery routes, such as spinal administration of opiate analgesics, is recommended. PMID- 2202209 TI - Use of infusion devices for epidural or intrathecal administration of spinal opioids. AB - The use of infusion devices for epidural or intrathecal administration of spinal opioids is described. The risks of infection and mechanical catheter complications, the need for escalating doses, reservoir volume, drug stability, and cost are practical considerations associated with use of both external and internal infusion systems. Use of patient criteria to identify suitable candidates for intraspinal administration of pain medication helps ensure successful management. The criteria for intraspinal delivery pumps are safety, accuracy, reliability, ease of management by the patient and the health-care professional, and compatibility of the drug with the pump components. The primary factors to consider when comparing pumps to be used for intraspinal delivery of pain medication are the volume and flow rate requirements of the devices. External portable infusion devices are classified according to the mechanism of operation into three primary groups: syringe pumps, peristaltic mechanisms, and elastomeric reservoir pumps. Portable patient-controlled analgesia pumps that have syringes, flexible reservoir bags, and elastomeric reservoirs have been developed. Implanted systems with flow rates that are preset at the factory make pain management more difficult when the patient requires changes or escalations in doses over time. A programmable implanted pump is available. Two advantages of continuous epidural or intrathecal infusion are (1) the peaks and valleys of pain relief with bolus injections are eliminated and (2) the need for multiple injections is reduced. Patient-controlled analgesia (PCA) pumps enhance the efficacy of continuous infusions by allowing the patient to administer bolus doses to control acute pain. PMID- 2202211 TI - Transmission of ring 14 chromosome from mother to two sons. AB - We report on a family with transmission of a ring chromosome 14 from an affected mother to her 2 sons. The mother was mosaic, 46,XX,r(14)/45,XX,t(14q21q). Both of her sons, affected by seizures and mental retardation, have the karyotype 46,XY,r(14). In considering the association of translocation 14:21 in the mother with ring 14, we postulate that either the ring chromosome was formed first and then opened with translocation of the partially deleted chromosome 14 to chromosome 21, or the 14:21 translocation was present first, then the chromosomes 14 and 21 broke apart, and the partially deleted 14 formed the ring. The published literature of cases of ring 14 is reviewed. PMID- 2202212 TI - Two siblings with Tel Hashomer camptodactyly and mitral valve prolapse. AB - A brother and sister with Tel Hashomer camptodactyly and mitral valve prolapse are described. Mitral valve prolapse is heterogenous, but appears to occur more frequently in individuals with connective tissue disorders. The presence of mitral valve prolapse as a component manifestation of Tel Hashomer camptodactyly suggests that abnormal connective tissue is a pleiotropic effect of the mutant allele. PMID- 2202213 TI - Prenatal diagnosis of skeletal dysplasia identified postnatally as hypochondroplasia. AB - A short-limb skeletal dysplasia was diagnosed prenatally at 35 weeks of gestation. After birth the infant was found to have hypochondroplasia. The parents are of average stature, and the child's disorder presumably occurred as a fresh mutation. This appears to be the first reported case of hypochondroplasia diagnosed prenatally as a "non-specific skeletal dysplasia" in the absence of a family history. Evaluation after birth showed that the infant, whose parents are of normal stature, has hypochondroplasia. PMID- 2202214 TI - Boomerang dysplasia. AB - Boomerang dysplasia is a recently delineated form of neonatally lethal dwarfism. A fourth case has been investigated and an increased range of phenotypic manifestations is documented in this article. So far all affected infants have been males and X-linked recessive inheritance is possible. Diagnostic criteria for Boomerang dysplasia are outlined. PMID- 2202215 TI - Multiple gastrointestinal atresias with imperforate anus: pathology and pathogenesis. AB - The syndrome of hereditary multiple gastrointestinal atresias is characterized by multiple and widespread atresias from pylorus to rectum, intraluminal calcifications on plain abdominal roentgenogram, and an invariably fatal course with an autosomal recessive mode of inheritance. We review 18 cases reported in the literature and one additional case in an infant with imperforate anus. The anatomical and histological characteristics of the atresias suggest a failure of recanalization of the embryonic intestinal lumen. The association between multiple atresias and imperforate anus supports the hypothesis that this disorder is a malformation syndrome caused by a defect in the development of the gastrointestinal tract. PMID- 2202216 TI - Bone dysplasias: the prenatal diagnostic challenge. AB - The prenatal diagnosis of bone dysplasias presents difficult challenges for the clinician involved in monitoring pregnancies. Such diagnoses highlight delicate ethical issues and may require difficult decision-making when the differential diagnosis includes a lethal bone dysplasia. Despite the rapid technological advances in ultrasonography, the ability to make prenatal diagnoses within this group of disorders is limited by the restricted ultrasonographic capability to appreciate fully the detailed fetal anatomy. However, we perceive that a significant further limitation involves the lack of a systematic protocol to guide the clinician in the ultrasonographic evaluation of a fetus suspected of having a skeletal dysplasia. In an attempt to aid the clinician who is evaluating these suspected pregnancies, we report here 8 cases and propose a model protocol for the ultrasonographic diagnostic approach to fetal skeletal problems in utero. PMID- 2202218 TI - Karyotype/phenotype controversy: genetic and molecular implications of alternative hypotheses. AB - Alternative explanations for aneuploid phenotypes are evaluated according to clinical and experimental predictions. The additive hypothesis views the diverse manifestations of aneuploidy as the simple sum of individual gene dosage effects. The interactive hypothesis views aneuploid characteristics as network properties of genes within and outside the aneuploid segment. The importance and historical context of this debate are emphasized, and the 2 hypotheses are contrasted in terms of their experimental predictions and explanatory power. In particular, the concepts of colinearity and continuity derived from single gene action are explicitly examined in human aneuploidy with the conclusion they are likely to be false assumptions. PMID- 2202217 TI - Expanded spectrum of findings in Marden-Walker syndrome. AB - Recently, we examined a small-for-gestational age infant with blepharophimosis, congenital contractures of elbows, hips, and knees, fixed facial expression, and hypotonia. These congenital anomalies are consistent with a diagnosis of the Marden-Walker syndrome. The infant also had an omphalomesenteric duct, left hypoplastic kidney, hypoplastic right lower lobe of the lung, and displacement of the larynx to the right; these anomalies have not been described previously in this syndrome. A summary of the clinical manifestations of the previously reported patients is presented. PMID- 2202220 TI - Malaria transmission and vector biology in Manarintsoa, high plateaux of Madagascar. AB - To evaluate the factors which determine the transmission level of falciparum malaria, entomological and parasitological surveys were conducted from October 1988 to February 1990 in Manarintsoa in the central highland plateaux of Madagascar. Mosquitoes were collected for 928 man-nights in pit shelters and indoor resting sites. Malaria vectors were Anopheles arabiensis and An. funestus, with no evidence of the presence of An. gambiae sensu stricto. Vectors were mainly exophilic and zoophilic. The index of stability was less than 1.5. The sporozoite rate was 0.11 for An. gambiae sensu lato and 0.47 for An. funestus. The transmission level was low, with an inoculation rate of 0.91 infective bites/person/year and an infection risk of 0.62. Malaria transmission occurs 7 months of the year in this area, from November to May. Human parasite rates fluctuated from 29% in October to 53% in May. PMID- 2202219 TI - Trisomy 13 syndrome and neural tube defects. AB - Abnormalities of the CNS, such as arhinencephaly or holoprosencephaly, are common findings in trisomy 13 syndrome. However, neural tube defects (NTDs) are rarely reported. A review of 267 patients in the literature on reported CNS developmental defects in trisomy 13 syndrome showed only 6 patients with lumbosacral NTDs. No case of encephalocele or anencephaly was found. We report on 3 patients with spina bifida from the records of 34 necropsies of karyotyped trisomy 13 syndrome, which were found among 403,710 births. PMID- 2202221 TI - Enzyme immunoassays for detection of malarial antigens in human plasmas by Plasmodium falciparum monoclonal antibodies. AB - The screening of blood donors for the detection of dangerous disease carriers is a mandatory requirement for blood transfusion centers. Enzyme immunoassay (EIA) is a suitable method for the examination of large populations. We describe a sandwich EIA allowing the detection of soluble malarial antigens in plasma using 11 mouse monoclonal antibodies. Among the 121 combinations tested, 2 were selected for their sensitivity and specificity. Both were applied to plasmas of (a) acute patients, (b) people living in malarious areas, (c) blood donors at risk (travelers), and (d) sedentary blood donors without risk. With 1 of the 2 combinations, the percentage of positive answers was 68.4% (n = 38) for a, 62.6% (n = 206) for b, 4.5% (n = 398) for c, and 0.8% (n = 485) for d; with the other combination, the percentage of positive answers was 68.4% for a, 46.1% for b, 1.5% for c, and 0% for d. Using 2 combinations simultaneously, the positive results were 94.7% for a, 70.4% for b, 5% for c, and 0.8% for d. The 2 assays are complementary and the pair can be used for maximum Plasmodium falciparum antigen recognition in prospective donors. PMID- 2202223 TI - Renal pathology in owl monkeys in Plasmodium falciparum vaccine trials. AB - Renal specimens of 16 owl monkeys (Aotus vociferans) were studied by light microscopy and immunohistochemistry during a vaccine trial with recombinant proteins of the ring-infected erythrocyte surface antigen (RESA) of Plasmodium falciparum. Deposition of IgG, C3, and P. falciparum antigens in the mesangium was demonstrated by the peroxidase anti-peroxidase (PAP) method. A relationship between the severity of parasitemia at the time of death and the presence of nephropathy was not apparent. PMID- 2202222 TI - Plasmodium falciparum infection rates in Anopheles gambiae, An. arabiensis, and An. funestus in western Kenya. AB - Mosquitoes collected monthly for 1 year from human habitations in the Kisumu area of western Kenya were identified by morphological characters as Anopheles gambiae Giles sensu lato (An. gambiae s.l.) or An. funestus. Of the mosquitoes collected, 7,244 (67%) of the An. gambiae s.l. and 8,511 (87%) of the An. funestus were tested by enzyme-linked immunosorbent assay (ELISA) for the presence of Plasmodium falciparum circumsporozoite (CS) protein. ELISA positivity rates were 8.2% for An. gambiae s.l. and 6.1% for An. funestus. Both An. gambiae and An. arabiensis were detected among 432 ELISA-positive and 668 ELISA-negative An. gambiae s.l. identified to species with a ribosomal DNA probe. The species specific infection rates were calculated to be 9.6% for An. gambiae and 0.4% for An. arabiensis. These results confirm that An. gambiae and An. funestus are the primary malaria vectors in western Kenya and that An. arabiensis is a relatively minor vector. PMID- 2202224 TI - Parasite-specific antibody response in Trichinella sp. 3 human infection: a one year follow-up. AB - Sera from patients with confirmed or suspected trichinellosis were examined for 1 year to detect the presence of parasite-specific antibodies (IgG, IgM, and IgE) using the enzyme-linked immunosorbent assay (ELISA). The indirect ELISA was used to detect specific IgG (ELISA-IgG) and specific IgM (ELISA-IgM); an amplified technique proved the most reliable for detection of specific IgE (a-ELISA-IgE). The immunofluorescence (IF) test was used to detect specific IgG (IF-IgG). The patients were from an outbreak of trichinellosis in Salsomaggiore (northern Italy) in 1986. The parasite was isolated and isoenzymatically typed as Trichinella sp. 3. The specificity of our tests was greater than 95%. During the 1st period of infection, all tests used gave practically the same positivity rate (78.2-86.9%). One year after infection, ELISA-IgG gave the highest positivity rate (55%). With the other tests, the positivity rate was 20-38.5%. At the 2nd month of infection, the IF-IgG test was the most discriminating in patients with confirmed and suspected trichinellosis, but ELISA-IgG proved the most reliable test for detecting specific immunoglobulins in late human trichinellosis infection. PMID- 2202225 TI - Surface molecules on Plasmodium falciparum-infected erythrocytes involved in adherence. AB - The identity of cell surface receptor molecules on Plasmodium falciparum-infected erythrocytes is of great interest since the functional sites involved in attachment to endothelial cells may be structurally conserved in wild isolates. Such conserved sites may represent suitable antigenic targets for a vaccine induced immune response that would block or reverse infected cell sequestration in vivo. Identification of the infected cell receptor sites may also lead to novel methods for treatment of acute cerebral malaria. We review the likely roles, either direct or indirect, for the participation of knob protrusions, malarial proteins expressed at the cell surface, and modified host membrane proteins in the specific receptor properties acquired by infected erythrocytes. PMID- 2202226 TI - In vitro and ex-vivo models of sequestration in Plasmodium falciparum infection. AB - Sequestration is the process by which erythrocytes infected with the mature forms of the malarial parasite Plasmodium falciparum disappear from circulation and accumulate within venules and capillaries of various organs and tissues. Several laboratory models of this phenomena are briefly described with a discussion of their values and shortcomings. PMID- 2202228 TI - Cerebral malaria in children: clinical implications of cytoadherence. AB - In endemic areas, most of the people who die from falciparum malaria are young children. Death is commonly preceded by coma (cerebral malaria). The possible role of cytoadherence in this clinical picture is considered. PMID- 2202227 TI - The pathology of human cerebral malaria. AB - Blockage of the cerebral microvasculature by Plasmodium falciparum-infected erythrocytes appears to be the principal cause of human cerebral malaria. Knobs which appear on the membrane of the infected erythrocytes adhere to the endothelium, causing the obstruction of cerebral microvessels. Protein molecules such as CD36, thrombospondin, and intercellular adhesion molecule-1, which are present on the membrane of endothelial cells, may act as receptors for the attachment of knobs of P. falciparum-infected erythrocytes. Each of these candidate host molecules for infected-cell recognition and attachment are expressed in microvessels of the human brain. The presence of HRP1 and HRP2 in the cerebral microvessels of cerebral malaria patients may indicate the involvement of knob proteins in the pathogenesis of cerebral malaria. Owl monkeys infected with P. falciparum do not develop cerebral malaria. There is no blockage of cerebral microvessels by infected erythrocytes and knob proteins are absent. These findings support the contention that cerebral microvessel blockage and the presence of knob proteins are the probable causes of cerebral malaria. PMID- 2202229 TI - [Dr. Hubert Schumann--60 years]. PMID- 2202230 TI - Diagnostic accuracy of computerized impedance plethysmography in the diagnosis of symptomatic deep vein thrombosis: a controlled venographic study. AB - The aim of our study was to evaluate the sensitivity, the specificity, and the positive and negative predictive values of a recently developed computerized impedance plethysmography (CIP) in the diagnosis of deep vein thrombosis (DVT); 117 consecutive outpatients with a clinical suspicion of DVT were evaluated. After informed consent was obtained, a CIP and, within twenty-four hours, a venography of the symptomatic lower limb were performed in each patient. The results of CIP were compared with the results of contrast venography, which was considered as the gold standard. As far as the diagnosis of both proximal and distal DVT was concerned, the accuracy of CIP was 88.5%; the sensitivity and specificity were 95.1% and 83.6%, respectively; the positive and negative predictive values were 81.2% and 95.8%, respectively. When the diagnosis of only proximal deep vein thrombosis was considered, the accuracy of CIP was 88.8%; the sensitivity and specificity were 97.1% and 83.6%, respectively; the positive and negative predictive values were 79.0% and 97.8%, respectively. The authors conclude that the newly developed CIP has a diagnostic accuracy similar to that of traditional impedance plethysmography. Moreover, being completely automated and portable, CIP can play an important role in the bedside diagnosis of DVT. PMID- 2202233 TI - Detection of the spatial distribution of late potentials by body surface mapping using forty-five unipolar, leads. AB - For evaluating the spatial location of late potentials (LPs), the authors designed a new system for the body surface mapping of signal-averaged, filtered ECGs using forty-five thoracic unipolar leads (5 x 9 array). The signals from patients with old myocardial infarction (MI, N = 7) and arrhythmogenic right ventricular dysplasia (ARVD, N = 1) were amplified and passed through a bandpass (100-300 Hz) filter. The departure maps, LP isopotential maps, and LP30 area maps were generated and superimposed. The LP30 duration was determined as the section between the filtered QRS endpoints and points thirty milliseconds (ms) before. Isopotential maps of the LPs showed distinct positive and negative regions. In 7 cases with MI, the extreme was related to the zones indicated by the departure maps, and the LP30 area maps also corresponded to the departure areas. In 1 case of ARVD, endocardial fragmented activity directly recorded at the right ventricle closely corresponded with the region on the LP30 area map. In conclusion, body surface LP isopotential maps and LP30 area maps may provide useful information concerning the spatial distribution of endocardial fragmentation. PMID- 2202232 TI - Real-time ultrasound in the diagnosis of acute deep venous thrombosis of the lower extremity. AB - One hundred twenty-six patients with clinically suspected acute deep venous thrombosis of the lower extremity (DVT) were examined comparatively with ultrasound and venography. In total, 174 lower extremity venograms were obtained. Ultrasonic examinations were performed on patients in the supine position. The venous segments were evaluated almost exclusively with transversal scanning. In the thigh, the only criterion for DVT was the reduced or absent compressibility of the venous lumen when gently compressed with the transducer. In the calf, normal unobstructed veins can usually not be viewed in the supine patient, whereas thrombotic veins appear as sonolucent, incompressible channels. Eight three of the 174 lower extremity venograms were positive for DVT. In the majority of cases (53 of 83) the thrombotic process had involved two or more segments in combination. The sites of involvement of the different venous segments were distributed as follows: 24 occlusions of the common femoral vein, 52 of the superficial femoral vein, 56 of the popliteal vein, and 71 of the calf veins. Ultrasound had a sensitivity of 100% for thrombosis of the common femoral vein, 96% for the superficial femoral veins, 98% for the popliteal vein, and 93% for the calf veins. For the entire lower extremity, in regard to the diagnosis of thrombosis, the overall sensitivity was 95%. In 90% the extension of the occlusion was foreseen correctly. In no cases were false-positive results reported. Thus the overall specificity was 100%. The authors conclude that real time ultrasound is a highly accurate method for the diagnosis of DVT of the lower extremity. It is the only indirect method capable of evaluating the venous system of the thigh, as well as that of the calf, with high accuracy. It should be the first choice of diagnostic imaging method in the diagnosis of deep venous thrombosis of the lower extremity. PMID- 2202231 TI - Placebo-controlled, double-blind study of the effect of verapamil in intermittent claudication. AB - The clinical effect of verapamil was tested in 24 patients with intermittent claudication in a randomized, placebo-controlled, double-blind, crossover study. Slow-release verapamil or placebo was given for two periods of three weeks. The walking distance, systemic blood pressure, and ankle-brachial blood pressure index were measured. Furthermore, a possible change in peripheral vascular tone was provoked by hyperventilation. The walking distance rose after both verapamil (40%) and placebo (31%) (p less than 0.01 for both) but tended to increase only after verapamil (7%) as compared with placebo. Blood pressure fell equally after both verapamil and placebo (p less than 0.05 for both). Verapamil did not influence the ankle-branchial blood pressure index. No signs of vasoactivity in the lower extremities were seen after hyperventilation. Although the greatest individual improvements in walking distance were seen after verapamil administration, it was not possible to predict positive responders among the patients. PMID- 2202234 TI - Carotid-cavernous sinus thrombosis caused by Aspergillus fumigatus: magnetic resonance imaging with pathologic correlation--a case report. AB - The authors describe a case of aspergillosis with carotid-cavernous sinus thrombosis diagnosed by use of magnetic resonance imaging (MRI). MRI may aid in early detection of intracranial fungal infection and potentially help decrease morbidity and mortality through the institution of early medical and surgical therapy. PMID- 2202235 TI - Fibromuscular dysplasia of the basilar artery: a case with brain stem stroke. AB - Fibromuscular dysplasia of the basilar artery is a rare and usually asymptomatic vascular disease with only 5 cases reported in the literature. A thirty-eight year-old man who developed ischemic neurologic symptoms of the brain stem due to dysplasia of the basilar artery is presented, and the clinical features, radiology, treatment, and prognosis of this disease are discussed in correlation with the current data. PMID- 2202237 TI - Epidemiologic panorama of dental occlusion. AB - The purpose of this study was to explore the possible significant sex difference in occlusion, provide information about the occlusal variation among Egyptians, and present an epidemiologic panorama of dental occlusion among different ethnic world populations. The hypothesis was that the occlusal variation is not independent of sex. A sample of 501 female and male adult subjects was studied. Normal occlusion, Angle's classification of malocclusion, and the Dewey-Anderson modifications for typifications were recorded. Chi-square tests were used. The results obtained from this study indicate that a significant sex difference in occlusion exists for normal occlusion, Angle Class I, and Angle Class III. Further, considering an anterior crossbite as the sole indicator of an Angle Class III malocclusion is erroneous; an anterior crossbite may exist in other classes, and Angle Class III type 1 (edge-to-edge) is more prevalent than either Class III type 2 (normal anterior overbite) or type 3 (anterior crossbite). Although numerically different, occlusal variation follows a universal general distributional pattern for most world populations. Some speculations are presented for clinical implications and for research suggestions. PMID- 2202236 TI - The long face syndrome and impairment of the nasopharyngeal airway. AB - Experimental evidence suggests that altered muscular function can influence craniofacial morphology. The switch from a nasal to an oronasal breathing pattern induces functional adaptations that include an increase in total anterior face height and vertical development of the lower anterior face. While some animals studies have suggested predictable growth patterns may occur, studies in human subjects have been much more controversial. Therefore, individual variations in response should be expected from the alteration of a long face syndrome patient's breathing mode. PMID- 2202238 TI - Rapid maxillary expansion in the treatment of nocturnal enuresis. AB - There is growing consensus that upper airway obstruction is a causative factor in nocturnal enuresis. This phenomenon has an unhappy history, although some surgeons in the past have touched on its treatment through the relief of upper airway obstruction. Only recently have sleep laboratory investigations presented a clearer, though still incomplete, picture of the etiology of nocturnal enuresis through disturbed sleep patterns. The obstruction is usually an adenoidal hypertrophy or, less commonly, an anterior nasal stenosis. While the otolaryngologist can readily cope with the former, surgical difficulties make treating the latter problematic. In many cases, the constriction can be reduced by rapid maxillary expansion. In the ten cases examined in this study, nocturnal enuresis ceased within a few months of maxillary expansion. PMID- 2202239 TI - Deferred consent: use in clinical resuscitation research. Brain Resuscitation Clinical Trial II Study Group. AB - Deferred consent, a new approach to the requirement for informed consent in clinical research, was used in a randomized clinical trial of brain resuscitation after cardiac arrest. Because patients were comatose and therapy had to be initiated immediately, traditional prospective consent usually could not be obtained. Using the deferred consent mechanism, family members were contacted after the first dose of experimental drug or placebo was administered and asked to consent for continued study participation. The vast majority of families were satisfied with the deferred consent mechanism. Their main concerns were about the safety of the experimental drug and whether the active drug or placebo was given. The concepts of randomization, blinding, and placebo-treated controls were generally not well understood. Although our experiences confirmed the impracticality of attempting to obtain traditional prospective consent in clinical resuscitation research, deferred consent was found to be a reasonable solution. PMID- 2202240 TI - The emergency department treatment of dyspepsia with antacids and oral lidocaine. AB - The treatment of dyspepsia in the emergency department often consists of antacid in combination with viscous lidocaine, even though the specific etiology of the pain is frequently unknown. The efficacy of lidocaine as a component of symptomatic therapy was evaluated in a randomized, patient-blinded protocol. Patients presenting to the ED with dyspeptic symptoms were randomized to receive 30 mL of antacid (Mylanta II), or 30 mL of antacid plus 15 mL of 2% viscous lidocaine (GI cocktail). Patients recorded their pain score on an 11-cm linear analog scale prior to and 30 minutes after treatment. Seventy-six patients were enrolled; three were excluded from analysis due to incomplete data. Thirty-four patients were randomized to receive antacid and 39 to receive GI cocktail. Patients rated their baseline pain at 6.4 +/- 2.8 cm in the antacid group and 6.7 +/- 2.7 cm in the cocktail group (P greater than .50). Improvement in pain score with treatment was 0.9 +/- 2.9 cm in the antacid group compared with 4.0 +/- 3.4 cm in the GI cocktail group (P less than .0001). Assessment of pain relief using a five-point rating scale also indicated greater relief with GI cocktail therapy compared with antacid alone (P = .004). No adverse effects were noted with either treatment. We conclude that a single dose of antacid and viscous lidocaine provides a significantly greater degree of immediate pain relief than antacid alone in patients with dyspepsia. PMID- 2202241 TI - Prophylactic effects of recombinant bovine interferon-alpha I1 on acute Salmonella typhimurium infection in calves. AB - The in vivo effects of a single prophylactic dose of recombinant bovine interferon (rBoIFN)-alpha I1 in calves with salmonellosis were investigated, using a Salmonella typhimurium infection model. Treatment with rBoIFN-alpha I1 reduced the degree of septicemia compared with that in control groups, and, in one experiment, using disease of reduced severity, body temperature was lower in treated calves than in controls. PMID- 2202243 TI - Airway hyperresponsiveness. Relevance of random population data to clinical usefulness. PMID- 2202242 TI - Effect of hypertonic vs isotonic saline solution on responses to sublethal Escherichia coli endotoxemia in horses. AB - Cardiovascular responses to sublethal endotoxin infusion (Escherichia coli, 50 micrograms/ml in lactated Ringer solution at 100 ml/h until pulmonary arterial pressure increased by 10 mm of Hg) were measured 2 times in 5 standing horses. In a 2-period crossover experimental design, horses were either administered hypertonic (2,400 mosm/kg of body weight, IV) or isotonic (300 mosm/kg, IV) NaCl solution after endotoxin challenges. Each solution was administered at a dose of 5 ml/kg (infusion rate, 80 ml/min). Complete data sets (mean arterial, central venous, and pulmonary arterial pressures, pulmonary arterial blood temperature, cardiac output, total peripheral vascular resistance, heart rate, plasma osmolality, plasma concentration of Na, K, Cl, and total protein, blood lactate concentration, and PCV) were collected at 0 (baseline, before endotoxin infusion), 0.25, 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after initiation of the endotoxin infusion. Blood constituents alone were measured at 0.5 hour and cardiovascular variables alone were evaluated at 0.75 hour. By 0.25 hour, endotoxin infusion was completed, a data set was collected, and saline infusion was initiated. By 0.75 hour, saline solutions had been completely administered. Mean (+/- SEM) cardiac output decreased (99.76 +/- 3.66 to 72.7 +/- 2.35 ml/min/kg) and total peripheral resistance (1.0 +/- 0.047 to 1.37 +/- 0.049 mm of Hg/ml/min/kg) and pulmonary arterial pressure (33.4 +/- 0.86 to 58.3 +/- 1.18 mm of Hg) increased for both trials by 0.25 hour after initiation of the endotoxin infusion and prior to fluid administration. For the remainder of the protocol, cardiac output was increased and total peripheral resistance was decreased during the hypertonic, compared with the isotonic, saline trial.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2202244 TI - Pulmonary aspergillosis in mice: treatment with a new triazole SCH39304. AB - The triazole SCH39304 was compared with amphotericin B and fluconazole for the treatment of pulmonary aspergillosis in corticoid-immunosuppressed mice intranasally challenged with 5 x 10(6) conidia of Aspergillus fumigatus. In vitro, the minimum inhibitory concentration (MIC) for fluconazole was greater than 80 micrograms/ml, for SCH39304 40 micrograms/ml, and for amphotericin B 0.29 micrograms/ml. Beginning 1 day after challenge, groups of 10 mice were treated orally, twice daily, for 15 days with Noble agar (control), SCH39304, fluconazole, or amphotericin B at various doses. For lung tissue counts of A. fumigatus, mice were similarly challenged and treated only for 5 days with SCH39304, fluconazole, or amphotericin B. Only SCH39304 significantly reduced the number of A. fumigatus in the lung. SCH39304 at doses of 5 mg/kg or higher significantly prolonged the survival of mice, as did amphotericin B at 3 mg/kg. Fluconazole did not significantly prolong survival at doses of 15 or 30 mg/kg. SCH39304 appears to be as effective as amphotericin B in murine pulmonary aspergillosis and warrants further evaluation for aspergillosis in humans. PMID- 2202245 TI - Incidence, risk, and prognosis factors of nosocomial pneumonia in mechanically ventilated patients. AB - Seventy-eight (24%) episodes of nosocomial pneumonia (NP) were detected in 322 consecutive mechanically ventilated patients admitted to a 1,000-bed teaching hospital from April 1987 through May 1988 to assess the incidence, risk, and prognosis factors of NP acquired during mechanical ventilation (MV). The risk and prognosis factors for developing NP during MV were studied using both univariate and multivariate statistical techniques. Multivariate analysis selected the following variables significantly associated with a higher risk for developing ventilator-associated pneumonia: more than one intubation during MV (p = 0.000012), a prior episode of aspiration of gastric content (p = 0.00018), a MV period longer than 3 days (p = 0.015), the presence of chronic obstructive pulmonary disease (COPD) (p = 0.048), and the use of positive end-expiratory pressure (PEEP) during MV (p = 0.092). The presence of an ultimately or rapidly fatal underlying disease (p = 0.0018), worsening of acute respiratory failure caused by pneumonia (p = 0.0096), the presence of septic shock (p = 0.016), an inappropriate antibiotic treatment (p = 0.02), and the type of intensive care unit (ICU) hospitalization (noncardiac surgery and nonsurgical ICU compared with post-cardiac surgery ICU) (p = 0.08) were those factors selected by a stepwise logistic regression analysis as independently worsening the prognosis. The overall fatality rate was 23% (73 of 322). The mortality of patients with NP was higher (33%; 26 of 78; p less than 0.01) when compared with fatality rates of patients without NP (19%; 47 of 244).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2202246 TI - The interrelationship among bronchial hyperresponsiveness, the diagnosis of asthma, and asthma symptoms. AB - Bronchial hyperresponsiveness (BHR) to inhaled histamine has often been cited as the gold standard in asthma diagnosis, but recently this has been questioned. This report assesses the relationship of BHR to asthma symptoms and asthma diagnosis in a large community-based sample of children. A total of 2,053 children 7 to 10 yr of age were randomly sampled from Auckland primary schools and assessed by a questionnaire and histamine inhalation challenge. In all, 14.3% had had asthma diagnosed, 29.6% reported having had one of the four respiratory symptoms in in the previous 12 months, and 15.9% had BHR (PD20 less than or equal to 7.8 mumol histamine). After a cumulative dose of 3.9 mumol histamine, the percent change in FEV1 from postsaline FEV1 was unimodally distributed, with those in whom asthma had been diagnosed dominating the severe end of the spectrum. However, 53% of those with BHR had no asthma diagnosis, and 41% had no current asthma symptoms. On the other hand, 48% of all subjects with diagnosed asthma and 42% of children with diagnosed asthma and current symptoms did not have BHR. Although severity of BHR tended to increase with wheezing frequency, all grades of severity (including no BHR) were found for any given frequency of wheeze. An existing diagnosis of asthma identified symptomatic children more accurately than did BHR, regardless of the criteria used for BHR or for "symptomatic" and irrespective of ethnic group. In conclusion, BHR is related to, but not identical to, clinical asthma. Bronchial challenge testing is an important tool of respiratory research, but cannot reliably or precisely separate asthmatics from nonasthmatics in the general community. PMID- 2202247 TI - Effect of inhaled furosemide on metabisulfite- and methacholine-induced bronchoconstriction and nasal potential difference in asthmatic subjects. AB - To evaluate the hypothesis that furosemide inhibits indirect bronchoconstrictor challenges by altering airway epithelial ion transport, we studied its effects on indirect bronchoconstriction induced by inhaled metabisulfite (MBS) and nasal potential difference (PD) in seven subjects with mild asthma. Its effect on direct bronchoconstriction by the inhaled muscarinic agonist methacholine (MC) was studied in six of these subjects. Each subject inhaled furosemide, 30 mg, in a randomized, double-blind, placebo-controlled fashion immediately before challenge with MBS (0.3 to 160 mg/ml in increasing doubling concentrations) and, in another study, MC (0.125 to 32 mg/ml) aerosols from a nebulizer attached to a dosimeter. PC20MBS and PC20MC, the concentration of each agent needed to lower FEV1 by 20%, were calculated by linear interpolation of the log dose-response curves. Furosemide had no effect on resting lung function, but it caused a significant threefold reduction in sensitivity to MBS (PC20MBS: GM +/- GSEM, 15.1 +/- 1.6 mg/ml after placebo and 40.7 +/- 1.7 mg/ml after furosemide; p less than 0.001) with a protective index of 64.8 +/- 10.7%. Furosemide caused no change in sensitivity to MC (PC20 MC:GM +/- GSEM, 2.37 +/- 1.61 mg/ml after placebo and 2.19 +/- 1.751 mg/ml after furosemide; NS). In a third study, furosemide, 30 mg, and placebo were inhaled through the nose in a randomized double-blind fashion immediately prior to inhalation of a PC20 concentration of MBS through the nose. Nasal PD was measured before and after placebo or furosemide, and again after MBS inhalation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2202249 TI - Smoking and smoking cessation. PMID- 2202248 TI - Effect of ozone inhalation on the response to nasal challenge with antigen of allergic subjects. AB - The effect of oxidant inhalation on allergic illness is of interest because allergic patients often report increased respiratory symptoms during episodes of poor air quality, and epidemiologic studies demonstrate an association between increased levels of the air pollutant ozone and exacerbations of asthma. The purpose of this study was to characterize the upper respiratory response to ozone inhalation in asymptomatic, allergic subjects and to determine whether ozone pre exposure increased the acute response to nasal challenge with antigen in these subjects. A group of 12 asymptomatic subjects with a history of allergic rhinitis were exposed in a randomized, cross-over design, at rest, on each of 2 days, separated by 2 wk, to 4 h of clean air or 0.5 ppm ozone in an environmental chamber. Following the exposure period, subjects underwent nasal challenge with four doses of antigen (1 to 1,000 PNU ragweed or grass). Symptoms were rated and nasal lavage performed after each dose. Measurement of histamine and albumin concentration and TAME-esterase activity and determination of cell counts and differentials were performed. Exposure to ozone caused significant increases in upper and lower respiratory symptoms, a mixed inflammatory cell influx with a sevenfold increase in naval lavage neutrophils, a 20-fold increase in eosinophils, and a tenfold increase in mononuclear cells, as well as an apparent sloughing of epithelial cells. There was a significant increase in nasal lavage albumin concentration on the ozone exposure day and a small increase in nasal lavage histamine concentration on both the ozone and clean air exposure days. TAME-esterase activity showed no significant increase overall, but increased at least twofold in 5 of 12 subjects. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2202250 TI - A concurrent increasing of natural antibodies and enhancement of resistance to furunculosis in rainbow trout. AB - In order to compare the respective roles of specific response and non-specific mechanisms in the enhancement of resistance to furunculosis, 2 groups of rainbow trout (Oncorhynchus mykiss) were immunized with supernatants of Aeromonas salmonicida or Escherichia coli cultures. The fish received 4 weekly intraperitoneal injections (70 micrograms of crude proteins). One control group was injected with phosphate-buffered saline, while another was untreated. Specific agglutinins were produced only in the fish immunized with A salmonicida supernatant. Polyspecific natural antibodies were measured using different antigens in an enzyme immunoassay. A significant rise (up to 3 times the mean titer of untreated controls) was observed in the 3 injected groups (even with PBS), which also displayed significant protection against experimental furunculosis (32 to 42% mortality versus 72% in controls). Thus, although the exact significance of natural antibodies still has to be confirmed, the importance of natural defenses and the difficulty in clearly inducing specific protection against furunculosis are confirmed. PMID- 2202251 TI - Skeletal muscularity and heart function in growing piglets. AB - Nine female piglets (about 15 kg), originating from a line with a low skeletal muscularity, were compared to 9 female piglets (about 15 kg) originating from a line with a high skeletal muscularity. Electrocardiogram-parameters (frequency rise, ST-elevation, heart rate expressed as mean values per h) were measured for 17 h with an ambulatory Holter-device. Dimensions of longissimus dorsi muscle (depth, circumference, surface, speed of ultrasound) were measured with an ultrasound device based on the pulse echo principle. Parameters, with respect to muscular dimensions, were statistically significant, differing between both lines, whereas, only the ST-elevation was significant, lower in the high skeletal muscularity line. The lower muscular depth was, the higher the ST-elevation and the higher the mean lowest heart rate were, and the lower the speed of ultrasound through the muscle tissue, by the higher the mean frequency rise. Hence, in growing piglets of about 15 kg, an impairment of heart function coincides gradually with a proportional higher development of skeletal muscularity. PMID- 2202253 TI - Viable endospores of Thermoactinomyces vulgaris in lake sediments as indicators of agricultural history. AB - Bacteria of the genus Thermoactinomyces form endospores with an extreme longevity in natural habitats. We isolated Thermoactinomyces sacchari from 9,000-year-old varved (annually laminated) sediment; thus, T. sacchari is probably one of the oldest known living organisms. More importantly, we tested and verified the hypothesis that there is a relationship between concentrations of dormant, viable endospores of T. vulgaris in lake sediments and the extent of agriculture in the catchments of the lakes. In surface sediments, low concentrations were recorded in forest lakes and the concentrations increased with increasing areas of cultivated land around the lakes. In varved sediment cores from three lakes, we found a temporal relationship between records of T. vulgaris endospores and the pollen of plants indicating agriculture. Endospores were very rare in sediments deposited before agriculture, ca. 1100 A.D. From then to between 1300 and 1700 A.D., a period with restricted cultivation, low but more regular rates of accumulation of endospores were recorded. High endospore accumulation rates were found with the subsequent agricultural expansion. This investigation confirms suggestions that this bacterium could be used as a paleoindicator for agricultural activity and be complementary to pollen analyses. Viable bacteria in continuous records of lake sediments are also potential material for evolutionary studies. PMID- 2202252 TI - Colorimetric enumeration of Escherichia coli based on beta-glucuronidase activity. AB - A medium containing a chromogenic substrate was developed for the enumeration of Escherichia coli on the basis of beta-glucuronidase activity. In this medium there was an inverse linear relationship between the log initial E. coli concentration and the time taken for the color to reach a threshold optical density of 0.05. This relationship applied even when the E. coli population contained 5% beta-glucuronidase-negative cells. Incubation at 44 degrees C reduced the time taken for color development and allowed the procedure to be used in the presence of a competitive microflora that outnumbered the E. coli population by a factor of 10(4). Sodium lauryl sulfate as an additional selective agent gave no significant improvement. In the analysis of environmental water samples, the technique gave a good correlation with a standard cultural method. The procedure shows promise as a simple method for testing the compliance of environmental samples with microbiological criteria for E. coli. PMID- 2202254 TI - Fuel alcohol production: effects of free amino nitrogen on fermentation of very high-gravity wheat mashes. AB - Although wheat mashes contain only growth-limiting amounts of free amino nitrogen, fermentations by active dry yeast (Saccharomyces cerevisiae) were completed (all fermentable sugars consumed) in 8 days at 20 degrees C even when the mash contained 35 g of dissolved solids per 100 ml. Supplementing wheat mashes with yeast extract, Casamino Acids, or a single amino acid such as glutamic acid stimulated growth of the yeast and reduced the fermentation time. With 0.9% yeast extract as the supplement, the fermentation time was reduced from 8 to 3 days, and a final ethanol yield of 17.1% (vol/vol) was achieved. Free amino nitrogen derived in situ through the hydrolysis of wheat proteins by a protease could substitute for the exogenous nitrogen source. Studies indicated, however, that exogenously added glycine (although readily taken up by the yeast) reduced the cell yield and prolonged the fermentation time. The results suggested that there are qualitative differences among amino acids with regard to their suitability to serve as nitrogen sources for the growth of yeast. The complete utilization of carbohydrates in wheat mashes containing very little free amino nitrogen presumably resulted because they had the "right" kind of amino acids. PMID- 2202255 TI - Starvation-specific formation of a peripheral exopolysaccharide by a marine Pseudomonas sp., strain S9. AB - The marine bacterium Pseudomonas sp. strain S9 produces exopolysaccharides (EPS) during both growth and total energy source and nutrient starvation. Transmission electron microscopy of immunogold-labeled cells demonstrated that the EPS is closely associated with the cell surface during growth (integral EPS), while both the integral form and a loosely associated extracellular (peripheral) form were observed during starvation. Formation and release of the latter rendered the starvation medium viscous. In addition, after 3 h of starvation in static conditions, less than 5% of the cells were motile, compared with 100% at the onset of starvation and approximately 80% subsequent to release of the peripheral EPS at 27 h of starvation. Inhibition of protein synthesis with chloramphenicol added before 3 h of starvation caused no increase in viscosity. However, addition of chloramphenicol at 3 h did not prevent the subsequent increase in viscosity displayed by S9 cells. The amount of integral EPS increased for both nontreated and chloramphenicol-treated S9 cells during the first hour of starvation, with a subsequent equal decrease. The chloramphenicol-treated cells, as well as cells of a transposon-generated mutant strain deficient in peripheral EPS formation, remained adhesive to a hydrophobic inanimate surface during the initial 5 h of starvation, whereas nontreated wild-type cells had progressively decreased adhesion capacity. During the initial 5 h of starvation, most of the nontreated cells but only a small fraction of the chloramphenicol-treated and mutant cells detached from the hydrophobic substratum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2202257 TI - Effects of cyclohexane, an industrial solvent, on the yeast Saccharomyces cerevisiae and on isolated yeast mitochondria. AB - Little information on the effects of cyclohexane at the cellular or subcellular level is available. In Saccharomyces cerevisiae, cyclohexane inhibited respiration and diverse energy-dependent processes. In mitochondria isolated from S. cerevisiae, oxygen uptake and ATP synthesis were inhibited, although ATPase activity was not affected. Cyclohexane effects were similar to those reported for beta-pinene and limonene, suggesting that the cyclohexane ring in these monoterpenes may be a determinant for their biological activities. PMID- 2202256 TI - Maintenance of plasmids pBR322 and pUC8 in nonculturable Escherichia coli in the marine environment. AB - Maintenance of plasmids pBR322 and pUC8 in Escherichia coli that was nonculturable after exposure to seawater was studied. E. coli JM83 and JM101, which contained plasmids pBR322 and pUC8, respectively, were placed in sterile artificial seawater for 21 days. Culturability was determined by plating on both nonselective and selective agar, and plasmid maintenance was monitored by direct isolation of plasmid nucleic acid from bacteria collected on Sterivex filters. E. coli JM83 became nonculturable after incubation for 6 days in seawater yet maintained plasmid pBR322 for the entire period of the study, i.e., 21 days. E. coli JM101 was nonculturable after incubation in seawater for 21 days and also maintained plasmid pUC8 throughout the duration of the microcosm experiment. Direct counts of bacterial cells did not change significantly during exposure to seawater, even though plate counts yielded no viable (i.e., platable) cells. We concluded that E. coli cells are capable of maintaining high-copy-number plasmids, even when no longer culturable, after exposure to the estuarine or marine environment. PMID- 2202259 TI - Application of the theory of adaptive polymorphism to the ecology and epidemiology of pathogenic yeasts. AB - The theory of adaptive polymorphism predicts that species occupying broad ecological niches will be phenotypically and genotypically more varied than those occupying narrow niches. It is suggested that this theory has direct relevance to the epidemiology of microbial pathogens in that environmental pathogens inhabit a broader niche and should be expected to exhibit greater variation than pathogens that are obligate commensals. This proved to be the case when one obligate commensal, the pathogenic yeast Candida albicans, was compared with other Candida spp. and an environmental pathogen, Cryptococcus neoformans. Further evidence of this relationship is derived from the literature. This observation adds further support to the theory of adaptive polymorphism, although the mechanisms of maintenance of polymorphism is asexually reproducing populations must be different from those in sexually reproducing populations. This observation may give important clues to the epidemiology of those infections for which it is not already known. PMID- 2202258 TI - Azoreductase activity of anaerobic bacteria isolated from human intestinal microflora. AB - A plate assay was developed for the detection of anaerobic bacteria that produce azoreductases. With this plate assay, 10 strains of anaerobic bacteria capable of reducing azo dyes were isolated from human feces and identified as Eubacterium hadrum (2 strains), Eubacterium spp. (2 species), Clostridium clostridiiforme, a Butyrivibrio sp., a Bacteroides sp., Clostridium paraputrificum, Clostridium nexile, and a Clostridium sp. The average rate of reduction of Direct Blue 15 dye (a dimethoxybenzidine-based dye) in these strains ranged from 16 to 135 nmol of dye per min per mg of protein. The enzymes were inactivated by oxygen. In seven isolates, a flavin compound (riboflavin, flavin adenine dinucleotide, or flavin mononucleotide) was required for azoreductase activity. In the other three isolates and in Clostridium perfringens, no added flavin was required for activity. Nondenaturing polyacrylamide gel electrophoresis showed that each bacterium expressed only one azoreductase isozyme. At least three types of azoreductase enzyme were produced by the different isolates. All of the azoreductases were produced constitutively and released extracellularly. PMID- 2202260 TI - Conditions for growing Mycoplasma canadense and Mycoplasma verecundum in a serum free medium. AB - Mycoplasma canadense and Mycoplasma verecundum were cultured in a serum-free medium containing bovine serum albumin, cholesterol, oleic acid, and palmitic acid in order to avoid the addition of horse serum. Growth was detected by measurement of A640 and by colony formation. The level of growth attained in this medium was less than that obtained in the horse serum-supplemented media, but colonies retained their distinctive morphology. PMID- 2202261 TI - [Polymerase chain reaction (PCR)--a novel tool for the molecular diagnosis of neoplasms]. AB - Polymerase chain reaction (PCR) is a novel tool for the in vitro amplification of DNA segments up to several kb. Repeated cycles of DNA synthesis by heat-stable Taq DNA polymerase enables to obtain more than 10(5) copies of the target sequence. Recently its enormous attitude of amplification has been applied for the detection of tumor-specific gene alterations. Examples include the detection of point mutation of RAS oncogenes at codons 12, 13, and 61 and the detection of minimal residual neoplastic cells in patients in complete clinical remission. Among many kinds of tumor specific gene translocations, BCR-ABL gene in t(9;22)(q34;q11) and BCL-2-IgH gene in t(14:18)(q32;q21) have been successfully PCR-amplified around their fused regions. In lymphoid malignancies gene rearrangements of T cell receptor chain or immunoglobulin heavy chain can be used as clonal markers for leukemic cells. PCR technique permits the detection of leukemia DNA at dilution of 10(-4) to 10(-6). Although further investigation of patients' follow-up in large scale is needed, this technique seems to hold promise for the monitoring of residual neoplastic cells. PMID- 2202262 TI - [Microscopic innervation of the spermatic ducts and testicle. IV. Testis]. AB - The presence of nerve fibers in the testicle of the rat has been investigated both in light (silver and osmium-iodide impregnations, and histochemistry for acetylcholinesterase) and electron microscope. Nerve fibers were found in the albuginea and close to the intertubular blood vessels. However, these were not observed at ultrastructural level. On the other hand, the Leydig cells do not have a direct innervation but nerve fibers containing large and small granular synaptic vesicles were observed in the vicinity (3,000 A). The authors discuss the possible control of the testicular function by the peripheral nervous system. PMID- 2202263 TI - [Present and future of research in the diagnosis and treatment of cancer]. PMID- 2202265 TI - [In situ individual extraction of the kidney from cadaveric donor for kidney transplant]. AB - A modified technique for harvesting cadaver kidneys for transplantation is described. Following en block perfusion, in situ individual--not monoblock- removal of the kidneys and their respective patches is performed to avoid complicated maneuvers that may stretch the vascular pedicle and compromise the graft. This modified technique has been utilized in over 100 procedures of kidney procurement for renal transplantation at the Puigvert Foundation. PMID- 2202264 TI - [Low-dose BCG in the therapy of superficial neoplasms of the bladder]. AB - The preliminary results of a randomized ongoing study performed in order to evaluate the efficacy and the relative toxicity of a low dose (75 mg). BCG regimen in the treatment of superficial bladder cancer were considered. Ninety eight patients (58 patients for prophylaxis of the recurrences of Ta-T1 papillary tumors; 40 patients for therapy of carcinoma in situ) received a 6-weeks course of 75 mg. BCG Pasteur vaccine. An additional course was given to non-responders. A maintenance therapy was administered in complete responders monthly for the first year and quarterly for the second. The prophylaxis group (TUR + BCG) was randomized vs TUR alone (40 patients = control group). Complete response in evaluated patients of the prophylaxis, control and therapy groups achieved 86%, 17% and 78%, respectively, after 18 months; 5%, 20% and 9% of patients, respectively, experienced tumor progression. As regards the toxicity, irritative disturbances (27%) and fever (16%) appeared significantly decreased in comparison with those reported in the literature. No major complications were experienced. In conclusion, the low dose (75 mg.) Pasteur BCG regimen used in our trial was effective as a prophylaxis against recurrent superficial papillary tumors and as a treatment of carcinoma in situ, with a significant decrease in toxicity. PMID- 2202266 TI - Benefits of an ultrasound-guided ESWL unit. AB - Ultrasound is ideally suited for imaging of renal calculi for extracorporeal shock wave lithotripsy. Ultrasound can localize radiolucent stones, monitor fragmentation in real time, and differentiate the stone from a stent. Its use significantly reduces the radiation exposure to patient and operator, which is particularly desirable in the pediatric patient. Furthermore, sonography-guided lithotripsy can reveal any incidental finding in the affected kidney that may require further evaluation and familiarizes the operator with this increasingly useful imaging method. The ultrasound-guided Sonolith 3000 with its enlarged ellipsoid aperture has a decreased energy focus size and voltage, permitting fragmentation with reduced anesthesia requirements. The initial extracorporeal shockwave lithotripsy (ESWL) machine, the Dornier H3, uses fluoroscopy for stone localization and treatment monitoring. Although this imaging method has the benefit of being familiar to urologists, it has some drawbacks, such as difficulty in imaging some types of stones and the radiation exposure of the operator and the patient. We have been using the Technomed Sonolith 3000 ESWL machine, which uses ultrasound to localize stones. During this experience, we have found a number of obvious and not so obvious benefits. For example essentially all calculi are echogenic, irrespective of their radiologic density. Moreover, with ultrasound, fragmentation can be monitored by real-time imaging, making determination of the treatment end point easier, and the stone and stent can be differentiated clearly. Ultrasound also can reveal other pathology and eliminates radiation exposure. Moreover, an ultrasound-guided ESWL unit familiarizes the operator with ultrasound techniques, and the same machine can be used for biliary lithotripsy. All of these features make ultrasound imaging for ESWL desirable. PMID- 2202267 TI - Computer assisted semen analysis not superior to routine analysis in distinguishing fertile from subfertile men. AB - The ability of the semen analysis either by routine methods (RSA) or computer assisted means (CSA) to predict male infertility was evaluated by determining the pregnancy rates during an 8-month span in a large group of infertile couples where a female fertility factor was identified and presumably corrected. The males were untreated. Not only was CSA less effective than RSA in predicting a male infertility factor, but also neither CSA or RSA seemed capable of identifying infertility unless severely abnormal. It would appear that there is definite need to find more accurate methods of evaluating the spermiogram. PMID- 2202268 TI - Comparison of two sperm preparation techniques using automated sperm motion analysis: migration sedimentation versus swim-up. AB - Migration sedimentation and spermatozoa swim-up techniques were used for obtaining spermatozoa from the semen samples of 39 infertile men. Concentration, percentage of motile sperm, velocity, linearity, and motility index of the sperm preparations obtained by both methods were compared using the CellSoft automated sperm motion analyzer. The mean velocity of the spermatozoa obtained after the migration sedimentation technique was significantly higher than that with swim-up technique. Since it is not necessary to centrifuge spermatozoa with the migration sedimentation technique, this method may be more desirable than other techniques using centrifugation. PMID- 2202270 TI - Tumor markers--expectations and possibilities. PMID- 2202269 TI - Are mycotoxins risk factors for endemic nephropathy and associated urothelial cancers? AB - Evidence supporting a role of mycotoxin, in particular ochratoxin A (OA) and citrinin, in the etiology of Balkan endemic nephropathy (BEN) and associated urinary tract tumours (UTT) is reviewed. Both diseases occur in subjects born and/or living in certain rural areas where home-produced and home-stored stable foods were found to be more frequently contaminated by the OA and citrinin. OA levels in blood and urine from patients with BEN or UTT were higher than in controls. OA and possibly other mycotoxins cause endemic porcine nephropathy, a disease with morphology and clinical course similar to those of BEN. OA was carcinogenic in two rodent species with kidney as a major target organ. Animals and strains phenotype as fast metabolizers of debrisoquine were more susceptible to OA-induced carcinogenicity. Among BEN/UTT patients, a greater proportion of fast metabolizers was reported. Although no epidemiological proof of a direct causal role of mycotoxins in BEN/UTT etiology has been presented, the data accumulated so far indicate a need for prospective studies in which mycotoxins as well as other risk factors should be considered. PMID- 2202272 TI - Modern development of imaging procedures in oncology. AB - From the oncologic point of view, imaging diagnostic techniques have been and will be of steadily increasing significance. This paper gives a survey of the present state of the art and of various aspects of current international trends in X-ray diagnostics, computed tomography, ultrasound and magnetic resonance. High tech developments raise the expenditures, so that the cost-benefit-relations have to be considered in future diagnostic strategies. Some aspects for further research tasks are mentioned. The aim of all improvements in imaging procedures is to increase the influence of diagnostic procedures on treatment planning and to improve the treatment results and, ultimately, the prognosis of cancer patients. PMID- 2202273 TI - Imaging techniques: state and future. AB - Technical progress has produced a variety of novel imaging techniques (digital projection radiography, X-ray-transmission computed tomography, sonography, single photon emission computed tomography, positron emission tomography, magnetic resonance imaging), and has enormously extended the diagnostic possibilities in industrialized countries. Further technological developments will be considered under three aspects: --Improvement of current imaging procedures and opening-up of new applications --introduction of new imaging techniques --progressive use of computer technology in imaging diagnostics [digital image generation, image processing, image archiving and communication systems (PACS)] Finally, several consequences emerging from these aspects will be discussed. PMID- 2202271 TI - Screening for early detection of cancer. AB - This article presents the general principles of screening for cancer which have rigorously to be judged before programmes can be introduced. As to cervical and breast cancer, there is good evidence that screening can be beneficial. On the other hand, with lung or colorectal cancer screening programmes cannot be recommended as efficient measures to control these diseases. PMID- 2202274 TI - Cumulative positivity rates of multiple blood cultures for Mycobacterium avium intracellulare and Cryptococcus neoformans in patients with the acquired immunodeficiency syndrome. AB - We examined the occurrence of low-grade Mycobacterium avium-intracellulare bacteremia and Cryptococcus neoformans fungemia in patients with the acquired immunodeficiency syndrome and the consistency of positive cultures obtained using a sensitive blood culture system (Isolator, E. I. Du Pont de Nemours, Wilmington, Del) for the recovery of these organisms. The blood culture records were reviewed, and the proportion of positive blood cultures yielding less than 1 colony-forming unit per milliliter of M avium-intracellulare or C neoformans was calculated. To determine consistency, a period of potentially detectable septicemia was defined as the period between 1 week before the first positive blood culture and the last positive blood culture, providing consecutive positive blood cultures were separated by less than 2 weeks. All positive and negative blood cultures obtained during the period of potentially detectable septicemia were considered in the data analysis. Overall, 40 (16.9%) of 236 cultures positive for M avium-intracellulare and 36 (57.1%) of 63 for C neoformans yielded less than 1 colony-forming unit per milliliter. Mycobacteremia was detected in 52 of 57 periods of potentially detectable septicemia in the first culture and in 56 of 57 in the first two (cumulative detection rates of 91.2% and 98.2%, respectively). Cryptococcemia was detected in 12 of 17 periods of potentially detectable septicemia in the first culture and in 15 of 17 in the first two (cumulative detection rates of 70.6% and 88.2%, respectively). Because of the sensitivity of the blood culture system and the consistency of M avium intracellulare bacteremia and C neoformans fungemia in patients with the acquired immunodeficiency syndrome, it appears that two blood cultures are sufficient for the detection of most septic episodes caused by these organisms. PMID- 2202275 TI - Mesenchymal chondrosarcoma. An immunohistochemical study. AB - Mesenchymal chondrosarcoma is an uncommon small-cell neoplasm of bone and soft tissue, the chondrogenic nature of which has been generally accepted. However, the phenotypic attributes of the small-cell population in this neoplasm have not been well characterized, and its relationship to "precartilage mesenchyme" remains unclear. In an attempt to address this issue, we performed an immunohistochemical analysis of nine cases, using antibodies to vimentin, S100 protein, Leu-7 antigen, neuron-specific enolase, synaptophysin, desmin, muscle specific actin, cytokeratin, and epithelial membrane antigen, and the avidin biotin-peroxidase complex (ABC) method. The small cells of mesenchymal chondrosarcoma failed to express S100 protein, whereas all components of the tumors (small cells, lacunar chondroblasts, and chondroid matrix) stained for Leu 7 antigen in six cases. Neuron-specific enolase was identified in the small cells of four cases and in the lacunar cells of seven. None contained desmin, actin, cytokeratin, epithelial membrane antigen, or synaptophysin. The immunophenotype of mesenchymal chondrosarcoma resembled that of embryonic cartilage and thus did not contradict the premise that this tumor was the neoplastic counterpart of fetal chondroid tissues. However, immunohistologic studies are not overly helpful in the differential diagnosis between mesenchymal chondrosarcoma and other small round cell lesions. PMID- 2202276 TI - Wegener's granulomatosis. Immunomicroscopic and ultrastructural study of four cases. AB - Four cases of Wegener's granulomatosis involving lung are reported in which immunomicroscopy demonstrated that the parenchymal and vascular infiltrates were composed primarily of T cells and monocytes. No IgG, IgA, IgM, or C3 was identified in pulmonary vessels or alveolar septa. Ultrastructural studies failed to demonstrate dense deposits in alveolar septal capillaries or interstitium. These findings indicate that a cellular immune mechanism is active in these forms of pulmonary vasculitis and that immune complex deposition does not play a role. PMID- 2202277 TI - A biochemical study of serine proteinase activities at local gingival tissue sites in human chronic periodontitis. AB - Serine proteinases have the potential to influence the degradation of connective tissue in chronic periodontitis, which may progress episodically at individual tooth sites. Elastase-, chymotrypsin- and tryptase-like proteinase activity in homogenized gingival tissue were measured using, respectively, the selective peptide substrates MeOSuc-Ala-Ala-Pro-Val-AFC. MeOSuc-Phe-Pro-Phe-AFC and Z-Ala Arg-Arg-AFC. Each tooth site was assayed separately and divided, where appropriate, into gingival tissue and granulomata. Elastase-like activity was detected in only about half of the sites and with large variations. Chymotrypsin like activity decreased with increasing pocket depth, clinical attachment level, gingival index and gingival bleeding index. Tryptase-like activity did not vary consistently with clinical measures. Chymotrypsin- and tryptase-like proteinase activity were much higher in gingival tissue than in granulomata. These effects are best explained by the likely influence (or lack of influence) of the endogenous serum and tissue inhibitors of serine proteinases, the different cellular origins of the enzymes, and their relative affinities for their substrates. PMID- 2202278 TI - The distribution of vasoactive intestinal polypeptides and calcitonin gene related peptide in the periodontal ligament of mouse molar teeth. AB - The distribution of VIP- and CGRP-containing nerve fibres was examined by indirect immunofluorescence. There were many such fibres in the lower third of the ligament, some around the blood vessel close to the socket wall. In the middle third of the ligament, some CGRP-containing fibers entered from the lateral wall of the socket; this type of fibre was more numerous in the lower third than in middle third. There were some VIP-containing fibres but no CGRP containing fibres in the ligament surrounding the furcation of the molar roots. PMID- 2202280 TI - Radiation oncology in Australia: another personal view. PMID- 2202279 TI - The effect of stannous and sodium fluoride on coronal caries, root caries and bone loss in rice rats. AB - Sixty rice rats (Oryzomys palustris) were divided by littermate into 3 groups of 20 each. The 3 groups received either SnF2 (1000 parts/10(6) F), NaF (1000 parts/10(6] or double-distilled water (control). Test solutions were topically applied to molar teeth, twice daily, for 7 days. All rats were also provided with double-distilled drinking water and diet 2000 ad libitum. Experiments ended after 9 weeks. Alveolar bone loss, root and coronal caries were recorded and scored. SnF2 significantly reduced bone loss (p less than 0.05), but NaF did not. Root caries was significantly different in all 3 groups (p less than 0.05). SnF2 and NaF both reduced coronal caries significantly (p less than 0.05) in comparison to the control. However, the fluoride groups were not significantly different from each other. SnF2 may influence root caries via remineralization and an antimicrobial effect of the stannous ion. PMID- 2202281 TI - Gastrointestinal hormones: from basic science to a clinical perspective. AB - The gastrointestinal tract is the largest endocrine organ in the body. However, gastrointestinal hormones are not confined to the gut and many of them are delivered to their target tissue by neural and paracrine routes as well as the circulation. Regulatory peptide is therefore a more appropriate term than gastrointestinal hormone. The functions of these regulatory peptides include effects on intake, digestion and absorption of food, and changes in gut secretions, motility and growth. Since these peptides do not act alone but in concert it has been difficult to ascribe particular functions to individual peptides. However, the recent and on-going development of specific regulatory peptide agonists and antagonists has resulted in major advances in our understanding of the physiology of these peptides. In turn these findings are creating new therapeutic avenues providing some return from all the research on these gastrointestinal regulatory peptides. The somatostatin derivative (octreotide or sandostatin) is the most obvious example. Although only approved in Australia for treatment of carcinoids and VIPomas, the prospects include treatment of other gastroenteropancreatic tumours, acromegaly, idiopathic diarrhoea, fistula closure, dumping, and ERCP or post-operative pancreatitis. A new gastrokinetic agent, that acts via the motilin receptor, is undergoing trials for the treatment of impaired gastric emptying. The trophic effect of gastrointestinal peptides has clinical significance. For instance, gastrin antagonists inhibit cell proliferation of colon carcinoma cell lines. Furthermore the trophic effect of gastrin must be considered when potent gastric acid inhibitors, which cause a reflex increase in gastrin, are used. The outlook is for more mammalian regulatory peptides to be discovered adding further to the complexity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2202282 TI - Gallstone pancreatitis: a proposed management strategy. AB - It has been usual practice to manage gallstone pancreatitis conservatively over the acute phase and to perform an elective cholecystectomy after an interval of 2 3 months. Because of the risks of recurrent pancreatitis, and in an effort to reduce the high morbidity and mortality associated with severe pancreatitis, there has been a trend towards early surgical intervention and, more recently, endoscopic sphincterotomy. From the Greenlane Hospital experience during 1979 1987, and from a review of recent literature, a strategy is proposed for the management of acute gallstone pancreatitis. PMID- 2202284 TI - Non-suture anastomosis: the historical development. AB - A wide range of devices for uniting the bowel has been invented. These are ligatures, prostheses, adhesives and staples. Denans' rings and Henroz' articulated rings were described in 1826, and Murphy's anastomosis button in 1892. Modern stapling began with Hultl in 1908 and Petz in 1924. Sophisticated stapling instruments were invented in Moscow by Androsov and others between 1950 and 1960. These were modified by Ravitch to produce, in 1967, a safe, disposable, presterilized, preloaded, interchangeable cartridge in a light instrument. The value of stapling is now beyond dispute. PMID- 2202283 TI - Painless split skin donor sites: a controlled double-blind trial of Opsite, scarlet red and bupivacaine. AB - A prospective randomized double-blind trial comparing Opsite alone, Opsite after application of bupivacaine, scarlet ointment dressing alone and scarlet ointment after bupivacaine was done to assess the effect of these four dressing regimens on split skin donor site pain and healing. Significantly less pain was reported by those dressed with Opsite and this was thought to be due to the immobility of an Opsite dressing. Many of the patients dressed with scarlet ointment felt no pain. It was concluded that movement of dressings is the main factor in pain production and that bupivacaine appeared to have no effect. There was no difference in healing rates between those treated with Opsite and those treated with scarlet ointment. It is concluded that using Opsite is a convenient way of preventing donor site pain, but that to gain maximum advantage from this it should not be applied under tension. PMID- 2202285 TI - Aerospace Medical Association. Directory issue. PMID- 2202287 TI - Radiation and hypothalamic-pituitary function. AB - In adults, hypopituitarism is a common consequence of external radiotherapy. The clinical manifestations may be subtle and develop insidiously many years after radiotherapy. Anterior pituitary deficiencies can therefore only be detected by regular testing, including dynamic tests of GH and ACTH reserve. Although the deficiencies most commonly develop in the order GH, gonadotrophins, ACTH then TSH, this sequence may not be predictable in an individual patient and comprehensive testing is therefore required. The tests should ideally be performed annually for at least 10 years after treatment or until deficiency has been detected and treated. It is not only the patients with pituitary disease who are at risk of developing hypopituitarism after radiotherapy. Any patient who receives a total dose of irradiation of 20 Gy or more to the hypothalamic pituitary axis is at risk of hypopituitarism, although the threshold dose may be lower than this. This is particularly important in the long-term survivors of malignant disease in whom endocrine morbidity may be relatively common and in whom this can be easily treated, with consequent improvement in quality of life. Whilst patients who receive a high total dose of irradiation are at increased risk of developing multiple deficiencies, a higher fraction size also increases the risk of anterior pituitary failure. There is good evidence that the earliest damage to the hypothalamic-pituitary axis after external radiotherapy is at the level of the hypothalamus. However, patients who undergo pituitary ablation with interstitial radiotherapy or heavy particle beams are likely to sustain direct damage to the pituitary. In these patients, the sequence in which individual pituitary hormone deficiencies develop is generally the same as that observed with the hypothalamic damage after conventional external radiotherapy. The increasing use of radiotherapy as a means of treatment for malignant disease means that new groups of patients with potential for endocrine dysfunction are emerging. Whole body irradiation in the preparation for bone marrow transplant is one such treatment and although hypothalamic-pituitary damage appears to be confined to GH deficiency in children, longitudinal experience is limited to date, particularly in adults. The treatment of malignant disease in childhood is of particular importance in terms of the delayed endocrine sequelae. The hypothalamic-pituitary axis may not be the only endocrine tissue damaged by treatment in these patients and management is therefore more complicated. In the growing child, the potential association of growth hormone deficiency, gonadal failure or premature puberty and thyroid dysfunction mean that expert endocrine supervision is essential for optimum long-term outcome. PMID- 2202286 TI - Mechanisms of hypercalcaemia of malignancy. PMID- 2202288 TI - Haemopoietic growth factors and haematological malignancies. PMID- 2202289 TI - Mechanisms of growth regulation of human breast cancer. PMID- 2202290 TI - The role of endocrine therapy in prostatic cancer. AB - When judged by randomized clinical trial, current endocrine therapies offer symptomatic relief to prostatic cancer patients for an average period of 1-2 years following initiation of therapy. Medical castration with LHRH analogues is a safe and effective way of achieving 'castrate' levels of circulating androgens without the undesirable aspects of surgery. While there is some evidence for the value of combined therapies using these agents in combination with anti-androgens for 'total androgen blockade' in some patients, overall this approach has not been shown to offer advantages over castration, either surgical or medical, alone in controlled trials. Secondary endocrine therapy does not offer convincing objective response rates, suggesting that disease progression is independent of androgens. PMID- 2202291 TI - Protection of gonadal function from cytotoxic chemotherapy and irradiation. PMID- 2202292 TI - [General principles of neural therapy. Review]. AB - As an introduction the five applications of the neural-therapy, which are treatment of locus dolendi, segment, neural structures, vascular system and irritation-centre (disturbing field) as well as some indications and forms of treatment are described by presenting mechanisms, partly well known, partly to be completed by further research. The central function of the vegetative nervous system is pointed out. PMID- 2202293 TI - Uptake and binding of radiolabelled phenylarsine oxide in 3T3-L1 adipocytes. AB - Phenylarsine oxide (PAO), a trivalent arsenical, has been shown to inhibit insulin-stimulated glucose transport in 3T3-L1 adipocytes, implicating vicinal dithiols in signal transmission [Frost & Lane (1985) J. Biol. Chem. 260, 2646 2652]. To assist in the direct identification of a PAO-binding protein which might be involved in this process, we have synthesized [3H]acetylaminophenylarsine oxide [( 3H]APAO) from the amino derivative of phenylarsine oxide (NPAO). To assess the inhibitory effect of the product, a dual labelling experiment was performed which showed that [3H]APAO inhibited insulin stimulated 2-deoxy[1-14C]glucose transport in 3T3-L1 adipocytes with a Ki of 21 microM, identical with that of the parent compound, NPAO. Further characterization revealed that over a wide concentration range, uptake of the labelled arsine oxide was linear. Although the dithiol reagent 2,3 dimercaptopropanol (DMP) reversed PAO-induced inhibition of transport, it had no effect on the uptake of [3H]APAO. In a simple fractionation experiment approx. 50% of the radioactivity was associated with the cytosolic fraction and 50% with the total membrane fraction. Identification of radiolabelled proteins by non reducing SDS/PAGE revealed fraction-specific binding, although many proteins were observed. Covalent modification was time-dependent and could be reversed by addition of DMP. These data further support a role for vicinal dithiols in insulin-stimulated glucose transport. Additionally, the probe described may offer a new means with which to identify the inhibitory protein or, more globally, to investigate mechanisms of action of vicinal dithiol-containing proteins. PMID- 2202295 TI - Utilization of the free energy of the reversible binding of protein and modifying agent towards the rate-enhancement of protein covalent modification. AB - An analysis is presented of the catalytic factors responsible for the rate enhancement that may be observed when a protein modification reaction is compared with a reaction of the same modifying agent with a model micromolecular compound exhibiting the same reactive group as the protein under study. It is seen that affinity-mediated rate-enhancement of protein modification is realized by the loss of activation entropy. On the assumption that attainment of maximal affinity mediated rate-enhancement presents with an activation entropy of the protein modification reaction equal to zero, whereas the activation enthalpy of the reaction remains unchanged, it is shown that the value for maximal affinity mediated rate-enhancement is equal to e-delta s++/R. Accordingly, protein modification reactions may be differentiated into (i) reactions the rate enhancement of which (relative to the reaction of the same modifying agent with a model compound) is primarily entropy-controlled and (ii) reactions the rate enhancement of which is primarily enthalpy-controlled. It is seen that modifying agents of low reactivity towards model compounds, but with a high, i.e. highly negative, activation entropy are better suited as prospective affinity-based protein-modifying agents, since the potential affinity-mediated rate-enhancement, and hence the selectivity, of these compounds is necessarily high. Kinetic and thermodynamic constants of the reaction of modifying agents with proteins, and with model compounds, and values of maximal affinity-mediated rate-enhancement, based on published data of the reaction of several modifying agents with model compounds, are presented and discussed. PMID- 2202294 TI - Translocation of the brain-type glucose transporter largely accounts for insulin stimulation of glucose transport in BC3H-1 myocytes. AB - Insulin-stimulated glucose transport was examined in BC3H-1 myocytes. Insulin treatment lead to a 2.7 +/- 0.3-fold increase in the rate of deoxyglucose transport and, under the same conditions, a 2.1 +/- 0.1-fold increase in the amount of the brain-type glucose transporter (GLUT 1) at the cell surface. It has been shown that some insulin-responsive tissues express a second, immunologically distinct, transporter, namely GLUT 4. We report here that BC3H-1 myocytes and C2 and G8 myotubes express only GLUT 1; in contrast, rat soleus muscle and heart express 3-4 times higher levels of GLUT 4 than GLUT 1. Thus translocation of GLUT 1 can account for most, if not all, of the insulin stimulation of glucose transport in BC3H-1 myocytes. On the other, hand, neither BC3H-1 myocytes nor the other muscle-cell lines are adequate as models for the study of insulin regulation of glucose transport in muscle tissue. PMID- 2202296 TI - Characterization of an internally initiated integrase protein of HIV-1 produced in E. coli. AB - In E. coli cells transformed by an expression vector for the production of the protease (PR) integrase (IN) of HIV-1, three vitally encoded proteins were produced: an 11-kDa protein and a 32-kDa protein identified by immunoassays as the mature PR and IN protein, respectively, and an additional protein 15-kDa in size that reacted strongly with an antiserum recognizing a region in the carboxyl half of the IN protein. The kinetics of its synthesis indicated that it was not a degradation product of p32-IN, rather it probably arose from internal initiation at an AUG codon in the middle of the IN gene. Amino terminal sequence analysis of the first 70 residues demonstrated a perfect match with those predicted from the nucleotide sequence, beginning with the methionine codon at position 154 of the integrase gene. PMID- 2202297 TI - Islet amyloid polypeptide (IAPP) does not inhibit glucose-stimulated insulin secretion from isolated perfused rat pancreas. AB - Islet amyloid polypeptide (IAPP) is a recently discovered pancreatic islet hormone which is stored with insulin in the secretory vesicles of beta cells. Several lines of evidence suggested that IAPP might affect glucose-stimulated insulin secretion and, therefore, might play a role in the development of impaired insulin secretion which is typical of type 2 diabetes. In this study, the effects of human IAPP (amide) on glucose-stimulated insulin secretion was evaluated in the isolated perfused rat pancreas. IAPP in concentrations from 5 x 10(-12) to 10(-7) M had no significant effects on insulin secretion. IAPP, therefore, does not appear to be a significant modulator of glucose-stimulated insulin secretion at concentrations that are physiologically relevant. PMID- 2202298 TI - Site-specific mutagenesis of PRD1 DNA polymerase: mutations in highly conserved regions of the family B DNA polymerase. AB - The PRD1 DNA polymerase is a small multifunctional enzyme containing three major conserved amino acid sequences shared by family B DNA polymerases. Thus, the PRD1 DNA polymerase provides an useful model system with which to study structure function relationships of DNA polymerase molecules. In order to investigate the functional and structural roles of the highly conserved amino acid sequences, we have introduced mutations into each of the 3 conserved regions of the PRD1 DNA polymerase. Genetic complementation study as well as DNA polymerase assay indicated that each mutation inactivated DNA polymerase catalytic activity, but not the 3' to 5' exonuclease activity. PMID- 2202299 TI - Enhanced MYCN oncogene expression in human neuroblastoma cells results in increased susceptibility to growth inhibition by TNF alpha. AB - Human neuroblastoma cells with normal expression of the endogenous MYCN oncogene were transfected with a vector containing an exogenous MYCN gene. The transfected cells expressed the exogenous MYCN at high levels and had acquired a phenotype resembling that of cells from advanced human neuroblastomas. Proliferation of the MYCN-transfected, but not of the untransfected, neuroblastoma cells was inhibited by low concentrations of recombinant human tumor necrosis factor alpha (TNF alpha). Our results suggest that TNF alpha could be useful for the treatment of advanced human neuroblastomas, in which high MYCN expression seems to be a causative factor. PMID- 2202300 TI - Thyroid hormone binding protein contains glycosylation site binding protein activity. AB - Several lines of evidence provided by other workers indicate that within the same species thyroid hormone binding protein, the beta-subunit of prolyl hydroxylase, and protein disulfide isomerase are the same protein. We sought to determine if glycosylation site binding protein, a lumenal protein of the endoplasmic reticulum, also has the same primary structure. To accomplish this the level of glycosylation site binding protein (GSBP) activity, measured by photolabeling with a glycosylation site peptide probe, was carried out in preparations of 3T3 cells and in E. coli transformed with human thyroid hormone binding protein cDNA. The results strongly support the idea that GSBP is identical to these other lumenal proteins of the endoplasmic reticulum. PMID- 2202301 TI - Natural regulatory mechanisms of insulin degradation by insulin degrading enzyme. AB - Insulin-degrading enzyme (IDE) accounts for most of the insulin degrading activity in extracts of several tissues and plays an important role in the intracellular degradation of insulin. Using newly developed sandwich radioimmunoassay for rat IDE, this enzyme was detectable in all tissues we examined and liver had the highest level of IDE. The ratio of insulin degrading activity to IDE concentration was roughly the same in liver, brain and muscle, however, twice as high in kidney as compared with other tissues. On the contrary, its degrading activity in these tissue extracts, including kidney, was completely lost after immunoprecipitation of IDE. These results suggest that IDE degrades insulin in the initial step of cleavage and that there are some mechanisms to regulate insulin degrading activity by IDE in the tissues. PMID- 2202302 TI - Multiple protein forms of the human breast tumor-associated epithelial membrane antigen (EMA) are generated by alternative splicing and induced by hormonal stimulation. AB - Cloning and sequencing of epithelial membrane antigen (EMA) has demonstrated the existence of a variable number of tandem repeats (VNTR) flanked by unique sequences, and alternative splicing has been proposed to result in secreted and membrane-bound antigenic forms. Antisense oligonucleotides, specific for the VNTR region and various alternative splice forms, were used as probes to define EMA transcripts in poly A+ RNA from a mucinous breast tumor cell line. The BT549 line has been shown to exhibit enhanced expression and secretion of EMA when the cells are cultivated in a medium supplemented with hydrocortisone and insulin, and Northern blot analysis demonstrated that EMA-related RNA transcripts are commensurately enhanced. As a result of the large increase in EMA RNA levels, two major transcripts in BT549 have been identified as coding for either the secreted or transmembrane EMA forms and two antigenic forms have been immunoprecipitated from BT549 cell layer and medium translation products. PMID- 2202303 TI - Negative regulator of pluripotent hematopoietic stem cell proliferation in human white blood cells and plasma as analysed by enzyme immunoassay. AB - This paper describes the analysis, by a highly sensitive and specific enzyme immunoassay (EIA), of AcSDKP, a tetrapeptide recently isolated from fetal calf bone marrow and subsequently purified and identified which substantially inhibits entry into cycle of hematopoietic pluripotent stem cells (CFU-S). This molecule has a marked protective effect in mice during anticancer chemotherapy with phase specific drugs and plays an essential role in maintaining CFU-S out of cycle in normal mice. Using acetylcholinesterase-AcSDKP conjugate as tracer, rabbit specific antiserum and 96-well microtiter plates coated with a mouse monoclonal anti-rabbit IgG antibody, this EIA allows detection of AcSDKP at 15 fmol levels with a coefficient of variation less than 10% in the 50-500 fmol range. When combined with high-performance liquid chromatography, this assay clearly reveals the presence of this peptide in normal human white blood cells whereas in supernatant from cultured lymphocytes and in plasma the immunoreactive material is distinct from standard AcSDKP. PMID- 2202304 TI - The effects of the endothelin family peptides on cultured osteoblastic cells from rat calvariae. AB - The activities of three isoforms of the endothelin (ET) family peptides, ET-1, ET 2 and ET-3, were studied in cultured osteoblastic cells from neonatal rat calvariae. All three isoforms induce stimulation of DNA synthesis and reductions in cellular alkaline phosphatase activity in a dose-dependent manner with the rank order of potency: ET-1 congruent to ET-2 greater than ET-3. The 125I-labeled ET binding and affinity-cross linking experiments show the presence of a single class of the ET binding sites with a more than 10-fold higher affinity for ET-1 and ET-2 as compared to ET-3. The endothelins dose-dependently stimulate the production of inositol phosphates and induce mobilization of Ca2+ with the similar relative potency to that for the receptor binding. These results indicate that osteoblastic cells possess the endothelin receptor with a high affinity for ET-1 and ET-2 that is coupled to phospholipase C, and that the endothelins modulate cellular functions via this receptor. PMID- 2202305 TI - Thyroid hormone analogue SKF L-94901: effects on amino acid and carbohydrate metabolism in rat skeletal muscle in vitro. AB - In summary, hyperthyroidism increased the rate of glycolysis and decreased glycogen synthesis in isolated incubated rat soleus muscle preparations. SKF 901 also increased glycolysis, but the stimulation was 5-fold less than in T3-treated muscles. Hyperthyroidism increased the rate of glutamine release from skeletal muscle, but SKF 901 did not affect glutamine metabolism. PMID- 2202306 TI - The American College of Rheumatology 1990 criteria for the classification of vasculitis. Patients and methods. AB - The American College of Rheumatology Subcommittee on Classification of Vasculitis of the Diagnostic and Therapeutic Criteria Committee developed classification criteria for 7 forms of vasculitis: polyarteritis nodosa, Churg-Strauss syndrome, Wegener's granulomatosis, hypersensitivity vasculitis, Henoch-Schonlein purpura, giant cell (temporal) arteritis, and Takayasu arteritis. The data collection methods, quality control, and analytic procedures used to derive the classification rules are discussed herein. PMID- 2202307 TI - The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss syndrome (allergic granulomatosis and angiitis). AB - Criteria for the classification of Churg-Strauss syndrome (CSS) were developed by comparing 20 patients who had this diagnosis with 787 control patients with other forms of vasculitis. For the traditional format classification, 6 criteria were selected: asthma, eosinophilia greater than 10% on differential white blood cell count, mononeuropathy (including multiplex) or polyneuropathy, non-fixed pulmonary infiltrates on roentgenography, paranasal sinus abnormality, and biopsy containing a blood vessel with extravascular eosinophils. The presence of 4 or more of these 6 criteria yielded a sensitivity of 85% and a specificity of 99.7%. A classification tree was also constructed with 3 selected criteria: asthma, eosinophilia greater than 10% on differential white blood cell count, and history of documented allergy other than asthma or drug sensitivity. If a subject has eosinophilia and a documented history of either asthma or allergy, then that subject is classified as having CSS. For the tree classification, the sensitivity was 95% and the specificity was 99.2%. Advantages of the traditional format compared with the classification tree format, when applied to patients with systemic vasculitis, and their comparison with earlier work on CSS are discussed. PMID- 2202308 TI - The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis. AB - Criteria for the classification of Wegener's granulomatosis (WG) were developed by comparing 85 patients who had this disease with 722 control patients with other forms of vasculitis. For the traditional format classification, 4 criteria were selected: abnormal urinary sediment (red cell casts or greater than 5 red blood cells per high power field), abnormal findings on chest radiograph (nodules, cavities, or fixed infiltrates), oral ulcers or nasal discharge, and granulomatous inflammation on biopsy. The presence of 2 or more of these 4 criteria was associated with a sensitivity of 88.2% and a specificity of 92.0%. A classification tree was also constructed with 5 criteria being selected. These criteria were the same as for the traditional format, but included hemoptysis. The classification tree was associated with a sensitivity of 87.1% and a specificity of 93.6%. We describe criteria which distinguish patients with WG from patients with other forms of vasculitis with a high level of sensitivity and specificity. This distinction is important because WG requires cyclophosphamide therapy, whereas many other forms of vasculitis can be treated with corticosteroids alone. PMID- 2202309 TI - The American College of Rheumatology 1990 criteria for the classification of hypersensitivity vasculitis. AB - Criteria for the classification of hypersensitivity vasculitis were developed by comparing 93 patients who had this disease with 714 control patients with other forms of vasculitis. For the traditional format classification, 5 criteria were selected: age greater than 16 at disease onset, history of taking a medication at onset that may have been a precipitating factor, the presence of palpable purpura, the presence of maculopapular rash, and a biopsy demonstrating granulocytes around an arteriole or venule. The presence of 3 or more of these 5 criteria was associated with a sensitivity of 71.0% and a specificity of 83.9%. A classification tree was also constructed. The criteria appearing in the tree structure were the same as for the traditional format, except there were 2 pathology criteria: one required the presence of granulocytes in the wall of an arteriole or venule, and the other required the presence of eosinophils in the inflammatory exudate. The classification tree was associated with a sensitivity of 78.5% and a specificity of 78.7%. PMID- 2202310 TI - The American College of Rheumatology 1990 criteria for the classification of Henoch-Schonlein purpura. AB - Criteria for identifying Henoch-Schonlein Purpura (HSP) and distinguishing HSP from other forms of systemic arteritis were developed by comparing the manifestations in 85 patients who had HSP with those of 722 control patients with other forms of vasculitis. By the traditional format of choosing different combinations of candidate criteria and comparing the combinations for their ability to separate HSP cases from controls, 4 criteria were identified: age less than or equal to 20 years at disease onset, palpable purpura, acute abdominal pain, and biopsy showing granulocytes in the walls of small arterioles or venules. The presence of any 2 or more of these criteria distinguish HSP from other forms of vasculitis with a sensitivity of 87.1% and a specificity of 87.7%. The criteria selected by a classification tree method were similar: palpable purpura, age less than or equal to 20 years at disease onset, biopsy showing granulocytes around arterioles or venules, and gastrointestinal bleeding. These were able to distinguish HSP from other forms of vasculitis with a sensitivity of 89.4% and a specificity of 88.1%. PMID- 2202312 TI - The American College of Rheumatology 1990 criteria for the classification of vasculitis. Summary. PMID- 2202311 TI - The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. AB - Criteria for the classification of giant cell (temporal) arteritis were developed by comparing 214 patients who had this disease with 593 patients with other forms of vasculitis. For the traditional format classification, 5 criteria were selected: age greater than or equal to 50 years at disease onset, new onset of localized headache, temporal artery tenderness or decreased temporal artery pulse, elevated erythrocyte sedimentation rate (Westergren) greater than or equal to 50 mm/hour, and biopsy sample including an artery, showing necrotizing arteritis, characterized by a predominance of mononuclear cell infiltrates or a granulomatous process with multinucleated giant cells. The presence of 3 or more of these 5 criteria was associated with a sensitivity of 93.5% and a specificity of 91.2%. A classification tree was also constructed using 6 criteria. These criteria were the same as for the traditional format, except that elevated erythrocyte sedimentation rate was excluded, and 2 other variables were included: scalp tenderness and claudication of the jaw or tongue or on deglutition. The classification tree was associated with a sensitivity of 95.3% and specificity of 90.7%. PMID- 2202313 TI - Statistical approaches to classification. Methods for developing classification and other criteria rules. PMID- 2202314 TI - Glycoprotein specificity of cold-reactive IgM antilymphocyte autoantibodies in systemic lupus erythematosus. AB - Sera from patients with systemic lupus erythematosus frequently contain IgM antibodies to glycoproteins of Mr 46,000 and approximately 200,000 isolated from nonionic detergent lysates of mature T cells by affinity chromatography with solid-phase wheat germ agglutinin. Autoantibodies of this specificity correlate strongly with the presence of IgM anti-T cell autoantibodies, as determined by independent indirect immunofluorescence and complement-dependent microcytotoxicity assays, and are specifically absorbed by incubation of patient serum with viable T cells. Collectively, the data suggest that gp46 and, to a lesser extent, gp approximately 200 represent major targets of IgM antilymphocyte autoantibodies in systemic lupus erythematosus. PMID- 2202315 TI - Ankylosing spondylitis in aborigines (guanches) of the Canary Islands. PMID- 2202316 TI - Very early aortic responses during atherosclerosis induction in rabbits: measurement by duplex ultrasound. I. Non-invasive study of aortic hyperresponsiveness to serotonin. AB - We report the use of a non-invasive ultrasound method to visualize and measure changes in serotonin reactivity of the abdominal aorta during the early stages of atherosclerosis development. Studies were performed at 0, 4, 8, and 14 weeks in New Zealand white rabbits fed a diet enriched with 0.5% cholesterol. Change in systolic vessel diameter at each examination was compared with changes in rabbits fed a control diet or rabbits on a diet enriched with cholesterol plus a concentrated marine lipid. After 4 weeks on the diets, the abdominal aortae of rabbit fed the cholesterol-rich diet displayed an enhanced vasoconstriction to serotonin (P less than 0.01). The enhanced vasoconstriction was observed prior to visible morphologic changes, and progressed when restudied at succeeding examinations. Morphologic abnormalities became evident at 8 weeks in cholesterol fed animals. Dietary supplementation with marine lipid, rich in polyunsaturated fatty acids, diminished the effect of the atherogenic diet on aortic vasoconstriction. PMID- 2202317 TI - Biofilm hydrogel dressing: a clinical evaluation in the treatment of pressure sores. AB - A new dressing for chronic wounds, BioFilm hydrogel dressing, was compared to a hydrocolloid dressing (HCD) control in a clinical trial involving 90 patients and 129 Stage I and II wounds (defined by Enis and Sarmienti). The testing sites included both acute care and extended care facilities. A comparison of healing response and functional characteristics of both dressings was part of this assessment. Biofilm dressings demonstrated a healing advantage over the HCD. In addition, clinicians judged that the hydrogel dressings were easier to use and had superior fluid management capability and product integrity with minimal disruption to the healing wounds. PMID- 2202318 TI - [The 25-year existence of the Society of Gastroenterology of East Germany.I. 200 years of gastric intubation--its significance in the development of gastroenterology]. AB - In an overview of the history of gastric intubation, the first use of a stomach tube in 1790 is reported, and the importance of the works of Kussmaul and his assistants as well as of Leube, Ewald, Boas, and Einhorn are specially stressed. With the development of new possibilities of investigation by means of the gastric tube gastroenterology began to emerge as a special field. PMID- 2202319 TI - [Drug-induced liver damage from the clinical viewpoint]. AB - Extensive drug-induced hepatic injury leading up to jaundice occurs relatively rarely. Generally it is not predictable, independent on dosage and irreproductible in animals. As a rule you find it in less than 0.1% of the patients taking the drug, whereas the degree may range up to heavy or lethal (e.g. for isoniazid, methyldopa, halothane). Pathogenetically reactive metabolites capable of producing cytotoxic and/or immune reactions may play a role. Obviously higher age, female sex and endogenous or exogenous alterations in hepatocellular drug metabolism are disposing factors. Drugs, to which our patients most frequently reacted, were dihydralazine alone or in combination with propranolol, and ketophenylbutazone. The lymphocyte transformation test proved diagnostically valuable although it cannot be considered to represent a generally reliable testing method for drug-induced liver disease. Clinical, laboratory and histological findings are typical with a wider range of drugs, but liver biopsy provides the most reliable criteria. Clinical suspicion and stopping the intake of potentially noxious drugs are of importance. The reexposition test should be reserved to exceptional cases. PMID- 2202320 TI - [Biotransformation in liver damage]. AB - Xenobiotics may produce liver damages. Vice versa primary liver diseases influence metabolism and elimination of drugs. The activity of the isoenzymes of the monooxygenase system which catalyze biotransformation reactions in the liver can be tested by model substances (Cyt P-450Pb: Metamizol, Cyt P-450MC: Caffeine, Cyt P-450db1: Debrisoquine). It can be influenced by estrogens, gestagens, smoking, alcohol. Only severe stages of liver diseases reduce the biotransformation of drugs. Thus in liver cirrhosis the excretion of unchanged furosemide is increased. The bioavailability of propranolol is changed by a reduced first pass effect in liver cirrhosis. In patients with drug hepatitis after dihydralazine 15 out of 17 patients are genetically slow acetylators and they show also a lower activity of phase I cytochrom P-450 catalyzed biotransformation reactions. The same holds true for patients with haemochromatosis. Determination of the 7-ethoxycoumarin-O-deethylase (ECOD) in liver biopsy samples allows the correlation of the decrease in biotransformation with the increase of liver cell necrosis, intraacinous fibrosis and structural changes. Possibly the changes in biotransformation caused by liver diseases are connected with a disturbed regeneration of the liver corresponding to the concept of the "streaming liver". PMID- 2202322 TI - [Effects of prostaglandins on toxic and inflammatory liver diseases. A short review]. AB - This short review deals with actions of prostaglandins (PG) and leukotrienes (LT) in liver injury. According to experimental data PGs of the E- and I-series seem to play an important role as metabolic, cytoprotective, antifibrogenic, immunomodulating and hemodynamic regulatory factors having interest in human pathology. In human cirrhosis with portal hypertension elevated PGI levels promote the formation of a collateral circulation. Some studies suggest that renal PGs could be involved in the regulation of renal hemodynamics in cirrhosis and have probably pathogenetic value in the development of the hepatorenal syndrome. LTs act as mediators of inflammatory liver reactions. Conclusively, one can predict that eicosanoid research will lead to some progress in clinical hepatology. PMID- 2202321 TI - [Liver parenchyma damage in immunosuppressed patients: diagnostic differentiation]. AB - Liver abnormalities are common complications in patients with immunosuppressed state iatrogenic or infectious induced. They are caused by infections due to hepatotropic viruses or by other infectious complications, drug induced or caused by rejections in patients after transplantation. Hepatic neoplasms have been associated with liver abnormalities, too. Problems in evaluation of liver abnormalities in these patients are discussed. PMID- 2202324 TI - The health risks of saccharin revisited. AB - Almost from its discovery in 1879, the use of saccharin as an artificial, non nutritive sweetener has been the center of several controversies regarding potential toxic effects, most recently focusing on the urinary bladder carcinogenicity of sodium saccharin in rats when fed at high doses in two generation studies. No carcinogenic effect has been observed in mice, hamsters, or monkeys, and numerous epidemiological studies provide no clear or consistent evidence to support the assertion that sodium saccharin increases the risk of bladder cancer in the human population. Mechanism of action studies in the one susceptible species, the rat, continue to provide information useful in assessing potential risk to the human from saccharin consumption. Unlike typical carcinogens which interact with DNA, sodium saccharin is not genotoxic, but leads to an increase in cell proliferation of the urothelium, the only target tissue. It also appears that the effect of saccharin is modified by the salt form in which it is administered, despite equivalent concentrations of saccharin in the urine. The chemical form of saccharin in the urine is unaffected, and there is no evidence for a specific cell receptor for the saccharin molecule. Changes in several urinary parameters, such as pH, sodium, protein, silicates, volume, and others, appear to influence the reaction of the urothelium to sodium saccharin administration. Silicon-containing precipitate and/or crystals appear to be generated in the urine under specific circumstances, acting as microabrasive, cytotoxic material. Using a mathematical model of carcinogenesis, which encompasses the temporal dynamics and complexity of the process at a cellular level, including spontaneous genetic transitions, it has been shown that the effects of sodium saccharin can be explained entirely in terms of its non genotoxic influence on cell proliferation. In interpreting these analytical studies in the human context, particularly as they pertain to the urinary milieu which appears to be pivotal in the effect of sodium saccharin, we are led to the conclusion that there is a threshold effect in male rats and that an effect on the human urothelium is unlikely at even the highest levels of human consumption. PMID- 2202325 TI - The concept of critical levels of toxic heavy metals in target tissues. AB - The high reactivity of heavy metals with biological systems is well documented, although some disagreement remains on the precise dose-effect relationships involved. This represents a question of considerable importance, especially in attempts to assess the risks of exposure. The implicit assumption is usually made that a threshold concentration of specific metals exists in the most sensitive target organ, so that an increased frequency of functional lesions will be expected if this threshold is exceeded. The threshold for the metal defines its so-called critical level, and this review was written in order to examine the theoretical and practical difficulties in establishing such a level. Among these may be cited, for instance, the dependence of what constitutes the target tissue on the speciation of the metal, the changes in apparent critical level with rate and route of metal administration, the short half-life of some of the metals as well as their compartmentation in the tissues, and the considerable initiation delay frequently preceding the appearance of lesions. For these and other reasons a useful approximate value for a critical concentration has only been proposed so far for the total Cd concentration in the renal cortex of chronically exposed human adults. PMID- 2202323 TI - [Drug-induced liver damage from the morphologic viewpoint]. AB - An overview about drug-induced liver injury is presented. The most frequent changes of the hepatocytes are those of the organelles, which are adaptive at the beginning, but in later stages they can develop to degenerative alterations leading to necrosis. Cases of drug-induced hepatitis simulating all types of non suppurative hepatitis are a major problem of diagnosis. Bile duct lesions can include pure cholestasis, cholangiolitis and destruction of intrahepatic ducts. Drug-induced vascular lesions including tumours can be found as isolated phenomenon or in association with other signs of drug-induced liver damage. Hyperplasia (focal or diffuse) and neoplasia of the liver can develop in the course of a longstanding application of some drugs. PMID- 2202326 TI - Risk assessment of carcinogenic and noncarcinogenic chemicals. AB - "Risk Assessment" is a general term used with increasing frequency by both scientists and regulators. Scientifically based risk assessments consider available toxicologic data when judging which agents pose a significant risk to the human population. The science of toxicology focuses on identifying potential hazards to human health using surrogate animal studies. Margins of Safety and establishment of ADIs (Acceptable Daily Intakes) are methods applied to animal test data to set "safe" levels of potential exposure. While the use of Safety Factors in development of the ADI can support a pragmatic conclusion of safety, this approach cannot provide estimates of the probability of harm or the degree of safety. Therefore, Quantitative Risk Assessment (QRA) methods using mathematical models have been advanced to extrapolate from animal exposures which are usually high to much lower human exposure levels where experimental response is absent. Such methodology has been applied primarily by U.S. regulatory agencies to experimental oncogenic responses to estimate the risks of chemical exposure. The present manuscript considers both methods for evaluation of chemical safety and focuses on the scientific merits and limitations of each. PMID- 2202327 TI - Effects of mainstream and environmental tobacco smoke on the immune system in animals and humans: a review. AB - This review evaluates the available information on the effects of mainstream and environmental tobacco smoke on the immune system in animals and humans. The primary emphasis is on mainstream smoke since little information is available on the effects of environmental smoke. The effects of mainstream tobacco smoke on the immune system in humans and animals are similar. Animals exposed to mainstream tobacco smoke for periods of a few weeks generally exhibit a slight immunostimulation. However, subchronic and chronic exposure studies indicate that immunosuppressive changes develop. Lymphocyte proliferation in response to the mitogens PHA and LPS is decreased, suggesting compromise of cell function. Antibody production can be suppressed. Smoke-exposed animals that are challenged with metastasizing tumors or viruses have been shown to exhibit a higher incidence of tumorigenic and infectious diseases, respectively. Localized immunological changes in the lung can include reduction of bronchus-associated lymphoid tissue and immunoglobulin levels. Smoking-related changes in the peripheral immune system of humans have included elevated WBC counts, increased cytotoxic/suppressor and decreased inducer/helper T-cell numbers, slightly suppressed T-lymphocyte activity, significantly decreased natural killer cell activity, lowered circulating immunoglobin titers, except for IgE which is elevated, and increased susceptibility to infection. The effects of environmental tobacco smoke on the immune system, in contrast to mainstream tobacco smoke, have just begun to be investigated and information available in the literature, to date, is limited. Immunoreactive substances are known to be present in environmental tobacco smoke, but to date, environmental tobacco smoke has been more closely associated with irritation than sensitization. A few studies have indicated a potential for environmental smoke-induced hypersensitivity and suppression of immunoregulatory substances. In contrast, other investigators have failed to detect immunological or other biological changes associated with environmental smoke. Clearly, more research is needed to resolve these differences. PMID- 2202328 TI - [Theoretical and practical aspects of globular sedimentation velocity]. AB - The following methods used to determine globular sedimentation rate (VSG) were reviewed: Westergren and Wintrobe techniques, Chattas micromethod, Sibora and Sediplast systems and z percentage sedimentation. Also included are the VSG phases and those factors which determine the aggregation of the red corpuscles whether they be plasmatic, globular or extrinsic. PMID- 2202330 TI - [The way from medical to physiological chemistry at the University of Gottingen, 1840-1940]. AB - In the nineteenth century chemistry was separated from medicine and reorganized as a "pure" academic science. Those left-over parts of chemistry that were more oriented towards medical application formed the nucleus of modern physiological chemistry, but could usually only exist in connection with other subjects. Especially the combination with physiology proved to be stable. Discipline building was delayed by the fact that a lot of physiologists resented a separation from physiology. Also in Gottingen physiological chemistry was attributed to the Physiological Institute, but initially still had close connections with the General chemical Laboratory. At the end of the nineteenth century a first attempt to establish itself as a discipline together with hygiene failed. Physiological chemistry stayed a part of physiology until 1939 when the Institute of Physiological Chemistry was finally founded. The Gottingen way is characteristic for the general establishment of the discipline in Germany. PMID- 2202331 TI - Ernst Klenk lecture, November 7, 1988. Patterns of DNA methylation in the mammalian genome. PMID- 2202329 TI - Changes of NGF level in mouse hypothalamus following intermale aggressive behaviour: biological and immunohistochemical evidence. AB - Nerve growth factor (NGF) immunoreactivity was detected in the hypothalamus of adult male mice. NGF-immunoreactive cell bodies were examined through consecutive brain sections, and it was found that most of the NGF-positive cells were located in the dorsomedial and mediolateral portions of the hypothalamus. Tissue culture bioassays showed that hypothalamic extract elicits neurite outgrowth from both chick sensory ganglia and rat superior cervical ganglia neurons, and that these effects are inhibited by addition of NGF antibodies. Our results also showed that intermale aggressive behaviour induced by 6-8 weeks of social isolation induces an NGF increase in the hypothalamic area, which is not abolished by sialoadenectomy, suggesting that the increased brain NGF is locally synthesized, and does not come from salivary sources. Likewise, the level of NGF in the hypothalamus of adrenalectomized fighting mice increased, although to a much lesser extent, when compared to hypothalamic levels of sham-operated fighting mice. The present results and a recent report showing that aggressive behaviour causes an increase of mRNANGF in hypothalamic areas are discussed in relation to a possible functional role of NGF in these brain structures. PMID- 2202332 TI - Fractionation of elastase-type enzyme activity in biological fluids using a centrifugal analyser. AB - We here describe a simple, rapid and sensitive spectrophotometric method for fractionation of elastase-type enzyme activity on a centrifugal analyser using the chromogenic substrate Suc-[Ala]3-pNA. For quantitation of metalloelastase and serine elastase, respectively, the method utilizes 20mM EDTA as ametalloenzyme inhibitor and the serine enzyme inhibitor soybean trypsin inhibitor (SBTI) in a final concentration of 2.5 g/l. Containing both serine- and metalloelastase, a pool of synovial fluids from patients with rheumatoid arthritis was used. The method is suitable for clinical studies on different body fluids or cell constituents. The investigation points out the necessity of using inhibitors when chromogenic substrates are used to measure elastase activity in biological fluids. PMID- 2202335 TI - Ocular cicatricial pemphigoid. AB - A series of 17 patients with ocular cicatricial pemphigoid (OCP) is described retrospectively. The importance of early recognition, especially of disease involving the medial canthus and caruncular region, diagnosis by biopsy, and adequate immunosuppressive and surgical therapy, are emphasised. A detailed grading scheme has been developed and this has enabled the authors to determine the success or failure of the therapy during the active treatment period. A combined ophthalmological and immunological approach to treatment can result in a successful visual outcome of this potentially blinding disease. PMID- 2202333 TI - [Use of reconstituted basal membranes for the study of invasion of human tumor cells: current status and future prospects]. AB - Tumor metastasis is the major cause of death of oncology patients. One of the characteristic properties acquired by the metastatic cell is the ability to cross basement membranes. These are compartments of extracellular matrix composed largely by collagen type IV, laminin and a heparan sulphate proteoglycan. Here we review the use of a reconstituted basement membrane (Matrigel) in the Boyden chamber assay (Chemoinvasion Assay) for the assessment of the invasiveness of tumor cells of human origin. The possibility of using this test for the rapid evaluation of human tumor specimens from operated patients is discussed. PMID- 2202334 TI - Inherited macular dystrophies: a clinical overview. PMID- 2202336 TI - Dithranol: a review of the mechanism of action in the treatment of psoriasis vulgaris. AB - Dithranol is highly effective in the treatment of psoriasis. The drug inhibits keratinocyte hyperproliferation, granulocyte function and, in addition, may exert an immunosuppressive effect. Free radicals, histamine, eicosanoids and platelet activating factor have been shown to be involved in dithranol-induced dermatitis, and the oxidation products of the drug are responsible for the staining. Our experimental data suggest that extracellularly generated oxygen free radicals are responsible for both the antipsoriatic and irritative effect of the drug. Furthermore, we could recently provide evidence that extracellularly generated superoxide anion radical also induces an active adaptation mechanism resulting in increased tolerance to dithranol upon repeated application. This adaptive process may explain the requirement for increasing dithranol concentrations to maintain the antipsoriatic efficacy, and also the beneficial effect of other antipsoriatic modalities such as UV-B on dithranol-induced dermatitis. The recognition of this adaptive mechanism may open future prospects to overcome some limitations concerning the practical use of dithranol. PMID- 2202337 TI - Interactions of respiratory pathogens with host cell surface and extracellular matrix components. AB - Adhesion of pathogens to proteins and glycoconjugates on the host cell plasma membrane or to components of the extracellular matrix is a critical early step in the initiation of infection. For intracellular pathogens, adhesion to the cell surface is a prerequisite to gaining entry into the cell. In all cases, adhesion to host tissue prevents elimination of the pathogens by normal clearance processes and may help the organism to evade immune surveillance by the host. Many laboratories are investigating the ligand binding specificities of bacterial receptors or adhesions and have described diverse binding specificities for adhesive proteins in the host extracellular matrix including laminin and fibronectin. Many bacteria also have adhesins that bind to carbohydrates occurring on glycolipids and glycoproteins in the apical membranes of epithelia in tissues that are targets for infection. Definition of these binding specificities and identification of the receptors that mediate adhesion may lead to development of a novel class of antibiotics whose mechanism of action is to compete with the endogenous ligands for binding to the pathogen receptors or to otherwise prevent adhesion to host tissues and thereby prevent infection. PMID- 2202338 TI - Organization and development of peptide-containing neurons in the airways. PMID- 2202339 TI - Bombesin-like peptides: from frog skin to human lung. PMID- 2202340 TI - Expression of granulocyte-macrophage colony-stimulating factor mRNA by inflammatory cells in the sarcoid lung. AB - T lymphocytes and alveolar macrophages accumulating in the lower respiratory tract of patients with pulmonary sarcoidosis are known to be activated to produce several cytokines, presumably leading to granuloma formation within the lung. We hypothesized that these cells produce colony-stimulating factors (CSFs), which have been shown to affect the proliferation and function of monocyte-/macrophage lineage cells. To test this hypothesis, we tried to detect mRNA encoding CSFs in cells obtained by bronchoalveolar lavage using a reverse transcription-polymerase chain reaction. Granulocyte-macrophage CSF (GM-CSF) mRNA was detected in five of six patients with pulmonary sarcoidosis, whereas it was detected in none of the five normal controls. Macrophage-CSF mRNA was detected in all subjects examined, and interleukin-3 mRNA in none. These results suggest some relation of GM-CSF to sarcoid lesion formation. PMID- 2202341 TI - Late radiation injury of the small intestine. Clinical, pathophysiologic and radiobiologic aspects. A review. AB - Transient symptoms due to injury of the intestinal mucosa occur in the majority of patients receiving radiation therapy for pelvic or intra-abdominal neoplasms. Late (chronic) radiation enteropathy, although less common, is a more serious condition, associated with high morbidity and mortality. The manifestations of late radiation enteropathy are primarily due to changes in compartments other than the mucosa, such as intestinal wall fibrosis and obliterating vascular sclerosis. As a result of recent clinical and experimental studies, considerable knowledge about the pathogenesis, dose-response relationship, and time-course of development of late radiation enteropathy has been obtained. Also, the advent of new animal models has facilitated studies of time-dose-fractionation relationships in the intestine. The present paper summarizes clinical, pathophysiologic, and radiobiologic aspects pertinent to the development of chronic intestinal radiation injury. PMID- 2202343 TI - Is it possible to predict the outcome of radiation therapy of head and neck cancer? AB - Methods for predicting the outcome of radiation treatment are discussed. The correlation of tumour decrease during irradiation with recurrence-free survival is poor. A reliable method for predicting the long-term result of radiation therapy is urgently needed. Methods using flow cytometry, electron microscopy and positron emission tomography with short-lived radiopharmaceuticals are under investigation. PMID- 2202342 TI - Primary irradiation, surgery or combined therapy in squamous cell carcinoma of the larynx. A comparison of treatment results from two centers. AB - We compared two groups of patients with squamous cell carcinoma of the larynx. Group 1 consisted of 483 patients treated from 1958 through 1978. Primary surgery was selected in 41% pre- or postoperative radiation therapy in 16% and primary radiation therapy in 43%. Group 2 consisted of 247 patients treated from 1978 through 1983. Primary surgery was selected in only 1.6%, pre- or postoperative radiation therapy in 23%, and primary radiation therapy, with surgery in reserve for residual or recurrent carcinoma, in 76%. Although the results were comparable for patients with early stage tumors in the two groups, significantly higher local-regional tumor control rates and corrected survival rates were recorded for patients with advanced tumors in group 2. More patients survived with a cancer free functional larynx, the surgical salvage rates were higher, the complication rates and the death rates lower in group 2 compared to group 1. PMID- 2202344 TI - Two dimensional echocardiography and Doppler in the right ventricular infarction. AB - Two dimensional and Doppler echocardiography provide reliable and valuable information in order to evaluate right ventricular function and associated complications in patients with right ventricular infarction. Right ventricular function in right ventricular infarction. There are a number of indirect findings that may support the noninvasive diagnosis of ischemic right ventricular dysfunction and right ventricular infarction: 1. Right ventricular dilatation: A right ventricular diastolic dimension greater than 8 mm/m2 is highly indicative of ischemic right ventricular dysfunction, provided that other causes of right ventricular dilatation, but the sensitivity of this findings is low (50%), the same is true for a RVDD/LVDD ratio greater than 0.63. 2. Right ventricular contraction abnormalities: Wall motion abnormalities constitute the most sensitive and specific echocardiographic findings in the right ventricular infarction. The most common site of involvement is the posterior wall, over 32 patients with right ventricular infarction, 60% present abnormalities confined to the posterior segment; in 30% there is also abnormal contraction of the lateral wall and 10% of the cases present asyneresys of the anterior, lateral and posterior segments. Those patients with the most severe right ventricular dysfunction presented a higher number of right ventricular wall segments with abnormal wall motion. Abnormalities in right ventricular contraction may still be present after evolution and normalization of the hemodynamic data of right ventricular infarction. These findings suggest that wall motion abnormalities can be more sensitive than the hemodynamic in detecting right ventricular infarction. 3. Paradoxical septal motion: Is a common findings after right ventricular infarction and has been attributed to volume overload and alterations in right ventricular compliance, near of 50% present abnormalities of septal motion and those patients with most severe ventricular dysfunction presented most frequently abnormal septal motion. Right ventricular infarction complications. Right ventricular aneurysm: In a series of 50 consecutive patients surviving an episode of right ventricular infarction, we could only find five (10%) with a true ventricular aneurysm. The segments included always the apex and in two cases a thrombus was identified inside its cavity. Functional right ventricular aneurysm may be found in a high percentage (10/50.20%) of patients with right ventricular infarction. Right ventricular thrombi: The identification of thrombi in the right heart is more difficult than in the left ventricle, due to the trabeculation of the right ventricular wall. We could only find 6 cases, in a series of 50 patients studied by two dimensional echocardiography. In all of the cases the ventricular wall adjacent to the thrombus presents contraction abnormalities.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2202348 TI - Section 47: Bradford 1925--United Kingdom 1988. AB - Surveys of the use of the powers of compulsory removal of elderly people who are not mentally ill--Section 47 of the 1948 National Assistance Act--have been conducted covering two four-year periods from 1974 to 1986. These data, which are not collected centrally, show a wide range in the frequency with which these powers are used, and it is argued that the main reason for this is that the criteria employed to decide whether or not to invoke the powers vary widely from community physician to community physician. It is argued that a review of this legislation is now essential. PMID- 2202346 TI - Hexose metabolism in pancreatic islet cells: the coupling between hexose phosphorylation and mitochondrial respiration. AB - The possible relevance of D-glucose phosphorylation by mitochondria-bound hexokinase to the control of respiration was examined in mitochondria prepared from either tumoral pancreatic islet cells (RINm5F line) or normal rat liver. In both systems, ATP generated by mitochondria exposed to ADP and succinate could serve as a substrate for the phosphorylation of D-glucose. However, after exposure to exogenous ADP in the presence of succinate, only mitochondria isolated from RINm5F cells displayed a sizeable increase in O2 consumption in response to a subsequent administration of D-glucose. In this respect, the discrepancy between mitochondria from islet cells and liver, respectively, was found to be attributable to the much lower hexokinase activity, relative to respiratory rate, in liver than in RINm5F cell mitochondria. It is speculated that the coupling between hexose phosphorylation and respiration in islet cells may prime the mitochondria to generate ATP during the early metabolic and secretory response to a rise in extracellular D-glucose concentration. PMID- 2202345 TI - [Usefulness of Doppler echocardiography in the diagnosis of complications in the acute phase of myocardial infarct]. AB - Doppler echocardiography, providing objective data on heart anatomy and cardiac function, is a diagnostic method of unquestionable value in the acute phase of myocardial infarction. In what concerns myocardial infarction complications; echocardiography permits: a) evaluation of ventricular function, by quantifying heart failure and establishing the diagnosis of ventricular aneurysm; b) it is the most reliable method in the diagnosis of thrombi, and c) it constitutes a fundamental diagnostic tool in mechanical complications: rupture of the heart structures and evaluation of valvular competence. a) Evaluation of ventricular function. The analysis of ventricular dimensions and segmentary wall motion abnormalities permits the quantification of the infarct size and its repercussion upon the cardiac function. Otherwise, left ventricular proto and end diastolic filling rates give an idea about ventricular diastolic function alterations. b) Ventricular thrombi. The incidence of ventricular thrombi in AMI is variable, depending on the site of infarction and the number of segments with wall motion abnormalities. By echocardiography it has been demonstrated that 40% of the anterior transmural myocardial infarctions and 10% of the inferior ones disclosed thrombi, although the incidence of systemic embolism is scarce and similar on both anterior and inferior infarctions: nearly 2% during the first month after infarction. The criteria that identify the embolic risk include: thrombus size over 2 x 2 x 2 cm, pediculated and mobile thrombi. On the other hand, right intraventricular thrombi incidence is rare nearly 5% of right ventricular infarctions and post-infarction pulmonary embolism is probably more related to peripheral venous thrombus than to an intraventricular one. c) Mechanical complications. Echocardiography enables the direct diagnosis of interventricular septum and papillary muscles rupture in about 80% of the cases and although ordinary does not provide direct data on free ventricular wall rupture, the detection of pericardial effusion with high density echoes, together with finding of free right ventricular and atrial wall collapse, gives 80% of sensibility and over 90% of specificity in the diagnosis of free ventricular wall rupture. Finally, Doppler echocardiography permits the diagnosis and quantification of mitral and tricuspid regurgitation secondary to a rupture of even a simple disfunction of the atrioventricular subvalvular apparatus. PMID- 2202347 TI - [Goldenhar syndrome: apropos of 2 cases]. AB - The arc branch syndrome are a group of diseases whose classification and etiology are unknown yet. We has 2 patients with Goldenhar's syndrome and we have studied the etiopathogenicity and treatment in these diseases. PMID- 2202349 TI - The medicalization of public health; the United Kingdom and the United States contrasted. PMID- 2202350 TI - The participation of neural crest derived mesenchymal cells in development of the epithelial primordium of the thymus. AB - The purpose of this study was to correlate the contributions by derivatives of the neural crest with the development of the epithelial primordium of the thymus. The monoclonal antibody E/C8 was used to localize derivatives of the neural crest in chick embryos. Neural crest was ablated by microcautery of neural folds. Evaluation of thymic development was carried out on serial sections of embryos sacrificed on the sixth day of incubation. The size of the epithelial thymic primordium was smaller in experimental animals than in shams. E/C8 immunoreactivity was concentrated around the periphery of the primordium. It was determined, by quantifying reaction product using the Core-SCAN computer color analysis program, that the amount of immunoreactivity was decreased after ablation of neural crest. Statistical analysis showed that the quantity of reaction product was positively and significantly correlated with the size of the thymic primordium. It is concluded that mesenchymal derivatives of the neural crest, through participation in the early development of the epithelial primordium, play an important role in thymic development, and therefore with development of the immune system. PMID- 2202351 TI - Epithelial cells with vacuoles containing 54,000 dalton sialoglycoprotein in the mouse epididymal duct. AB - Epididymal ligation in the mouse induced unusual cells, called peculiar pale epithelial cells (hereafter, pale cells), specifically in the epithelium of the corpus epididymidis (ABE et al., 1982a, b). These pale cells had vacuoles with long microvilli on their inner surface. In this study, we found that the vacuoles of the pale cells occurred in normal mice and contained epididymal specific glycoprotein, sialoglycoprotein of 54,000 dalton (SGP54). This was elucidated by indirect immunofluorescence and avidin biotin complex techniques using monoclonal antibody T21 which specifically recognizes SGP54. These immunoreactive pale cells occurred in the distal caput and proximal corpus of the epididymidis. The relationship between the pale cell and SGP54 is discussed. PMID- 2202352 TI - Discrimination between HIV-1 and HIV-2-seropositive individuals using mouse monoclonal antibodies directed to HIV transmembrane proteins. AB - Mouse monoclonal antibodies directed against the transmembrane proteins of HIV-1 or HIV-2 provided site-directed, unambiguous discrimination between HIV-1 and HIV 2 antibody-positive sera, when employed in immunoassays as competitive probes against serum antibodies. These monoclonal antibodies mapped to epitopes outside of the well-characterized immunodominant regions (IDR) of the transmembrane proteins. The monoclonal competitive immunoassay was a superior method for discrimination compared with immunoprecipitation of metabolically radiolabeled HIV envelope glycoproteins, Western blot against viral envelope glycoproteins, or noncompetitive enzyme immunoassays employing HIV recombinant transmembrane proteins or synthetic IDR peptides as serological targets. The monoclonal competitive assay was not affected by antigenic cross reactivity or nonspecific reactivity exhibited by selected serum samples toward envelope proteins or peptides, respectively. Results of the monoclonal competitive immunoassay were supported by results of a peptide inhibition assay employing free IDR peptides in competition with IDR peptides on a solid support for binding of serum antibody. IDR peptide inhibition clearly demonstrated non-cross-reactive antigenic specificity of sera toward either the HIV-1 IDR or the HIV-2 IDR. The monoclonal competitive assay also identified samples containing antibody to both HIV-1 and HIV-2 transmembrane proteins. Analysis of these samples by IDR peptide inhibition indicated they contained two distinct, non-cross-reactive populations of antibodies, one directed to the HIV-1 IDR and the other directed to the HIV-2 IDR. PMID- 2202354 TI - [Choledocholithiasis in non-cholecystectomized patients (gallbladder in situ): a therapeutic dilemma]. PMID- 2202353 TI - 2,3 Dimercapto-1-propanol inhibits HIV-1 tat activity, viral production, and infectivity in vitro. AB - We have examined the effect of 2,3 dimercapto-1-propanol (DMP), which is known as an anti-heavy metal-poisoning drug, against human immunodeficiency virus type 1 (HIV-1). We demonstrate that DMP inhibited transactivation directed by tat protein, which is a metal containing transcriptional transactivating factor and also interfered with viral production. Furthermore, treatment and pretreatment of cells with DMP strongly reduced their sensitivity for HIV-1 infection through unknown mechanisms. These results indicate that DMP reveals pleuripotent effects on HIV-1 infection and production in vitro and thus may provide an exploitable hypothesis for designing new drugs against AIDS. PMID- 2202355 TI - [High flow medullary venous malformation with aneurysm on the proximal artery--a case report]. AB - Medullary Venous Malformation with an aneurysm is uncommon and only 4 cases have been reported in previous papers. We reported a case of a medullary venous malformation (MVM) of the frontal lobe with an aneurysm on its proximal artery. A 48 year old female with numbness of right fingers visited our hospital. On the CT scan, an abnormal enhanced area was found inside the left frontal lobe. The left carotid angiography showed both of an aneurysm around A com A in early arterial phase, and "MVM with early blush" in capillary-early venous phase. MRI showed linear signal void crossing the cortex to join paraventricular low intensity area (LIA) with slight cortical atrophy on sagittal slice. The CBF study by Xe-SPECT proved a high flow lesion, with mean CBF 69 (left), 59 (right) mg/100 g brain/min, Protective operation only for aneurysm was performed. The MVM in our case was proved to be a "high flow-low resistance system" by CBF study, although MVM has been considered a "low flow system". Reviewing papers, there were 3 cases of "high flow MVMs" confirmed by the measurement of CBF, all of them were large sized (greater than 4 cm) and with early blush angiographically. We conclude that large sized MVM with early blush needs hemodynamic inspection and special care to prevent "high flow MVMs" from hemorrhage and the steal. PMID- 2202356 TI - Terminal differentiation of osteogenic cells in the embryonic chick tibia is revealed by a monoclonal antibody against osteocytes. AB - Monoclonal antibodies against the surface of embryonic osteogenic cells have been used to characterize the sequence of transitions involved in the osteoblastic cell lineage. These previous data identified distinct cell stages within the osteogenic lineage, but were incomplete. To further refine and extend these observations, additional monoclonal antibodies were generated against the surface of osteogenic cells by immunizing mice with a heterogeneous population of chick embryonic bone cells. Supernatants from growing hybridoma colonies were immunohistochemically screened against frozen sections of stage 35 (day 9.5) chick tibiae. One cell line, SB-5, which secretes an antibody against the surface of osteogenic cells was successfully cloned, stabilized, and immortalized. Studies on the developmental progression of osteogenesis in the embryonic chick tibia reveal that cells within the lineage stages from Pre-Osteoblast to Secretory Osteoblast were never observed to react with antibody SB-5 at any time. By contrast, strong cell surface immunoreactivity was present on mature osteoblastic cells as they became Osteocytes. Furthermore, in cultures of osteogenic cells derived from embryonic calvaria or tibiae, cells possessing the SB-5 antigen on their surface displayed a morphology remarkably similar to that of Osteocytes found in situ. Double immunofluorescent staining of developing chick tibiae with SB-5 and SB-2, a monoclonal antibody directed against the surface of Secretory Osteoblasts, indicates that these cells proceed through an intermediate lineage step before becoming terminally differentiated Osteocytes. This transitory cell state is characterized by the simultaneous cell surface binding of antibodies SB-2 and SB-5, and is referred to as the Osteocytic Osteoblast stage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2202357 TI - Wrist fracture, heel bone density and thoracic kyphosis: a case control study. AB - The heel bone density measured by Broadband Ultrasound Attenuation (BUA), the thoracic kyphosis measured by a Kyphometer, height, and weight were compared between 294 women over 49 years of age who sustained a wrist fracture and 294 age matched women who had not previous wrist, hip or spine fracture. The BUA was significantly less in the women who had wrist fracture (p less than 0.0005), though there was a considerable overlap between the two populations. The women with wrist fracture had significantly greater thoracic kyphosis (p less than 0.0005) and smaller stature (p less than 0.0005). There was no significant difference in weight. There was a significant tendency (p less than 0.0005) for women in the fracture patient group to have both poor BUA and greater kyphosis. PMID- 2202358 TI - Alzheimer's disease. AB - Alzheimer's disease (AD) is a debilitating and progressive disease that can affect dental practice in a number of ways. Not only will increasing numbers of AD patients be treated by dentists in the future but the dentist and members of his family may also be unfortunate enough to become affected. In the United Kingdom, nearly 10% of the population over 65 years of age, and more than 20% of those over 80 years develop progressive deterioration of memory, resulting in a breakdown of intellectual capacity and personality. More than half of those are suffering from AD. The purpose of this review is to describe the aetiology and behavioural aspects of this distressing disease and to highlight some problems that the dentist may encounter when treating those patients. PMID- 2202359 TI - Ribozymes versus HIV. PMID- 2202360 TI - RITA trial protocol. PMID- 2202361 TI - Ultrasound in the diagnosis of diaphragmatic paralysis after operation for congenital heart disease. AB - Phrenic nerve palsy is a recognised complication of operation for congenital heart disease in children. The accuracy of ultrasound in assessing diaphragmatic motion was prospectively compared with fluoroscopy in 16 patients in whom phrenic nerve palsy was suspected. Ultrasound successfully identified the five patients with phrenic nerve palsy; there were no false positive or false negative diagnoses. Ultrasound was as effective as fluoroscopy in the diagnosis of abnormalities of diaphragmatic motion. PMID- 2202363 TI - R.M. Marquis and Edinburgh cardiology. PMID- 2202362 TI - Percutaneous transluminal coronary angioplasty: catheter technology and procedural guidelines. PMID- 2202364 TI - Diabetes mellitus: impact on pregnancy. AB - Diabetes Mellitus as a predisposing condition in pregnancy places the mother and fetus at increased risk for complications. Nevertheless, a successful pregnancy with a healthy baby is a realistic goal for most diabetic women today. The emphasis is on maintaining good control of blood glucose levels before conception and during pregnancy to minimize the risks. This article explains the physiology of diabetes and pregnancy and the metabolic changes that occur. It outlines the plan of management during pregnancy and the postpartum period and presents a review of the major complications that could affect the infant of the diabetic mother. A multidisciplinary team approach is also stressed as a positive influence affecting the outcome of a diabetic pregnancy. PMID- 2202366 TI - Chronic renal disease and pregnancy. AB - Women who have chronic renal disease are at increased risk for maternal and fetal morbidity and mortality during pregnancy. The severity of the renal disease is correlated with the degree of morbidity and mortality. Chronic renal disease ranges from asymptomatic bacteriuria (ASB) to end stage renal disease requiring hemodialysis and/or renal transplantation. Pregnant women with chronic renal disease require specialized nursing care. Communication between obstetrical nurses and renal nurses is extremely important to ensure holistic care of these patients. PMID- 2202367 TI - Asthma in pregnancy. AB - Asthma is one of the more common medical disorders in pregnancy. Goals of management include prevention of acute asthmatic attacks while maintaining a safe intrauterine environment for the fetus. The following article outlines the interplay between asthma and pregnancy as well as current treatment modalities. This information is vital for nurses caring for obstetrical patients and their families. PMID- 2202365 TI - Seizure disorders and pregnancy. AB - Care of a pregnant woman with seizure disorder is a challenge for the maternal child nurse. Epilepsy affects 0.5% of all pregnant women. These women face possible risks of increased seizure frequency, reduced anti-epileptic drug levels, and, although rare, life-threatening status epilepticus. Their neonates are at risk for congenital malformations and possible bleeding disorders. Comprehensive nursing care based on a sound understanding of medical, pharmacologic, and nursing principles is crucial for optimal maternal/neonatal outcomes. Specific nursing implications and interventions during the preconceptual, prenatal, intrapartal, and postpartal periods are presented. PMID- 2202368 TI - Systemic lupus erythematosus: obstetric and neonatal implications. AB - Systemic lupus erythematosus (SLE) is a collagen vascular disease that may have a tremendous impact on pregnancy. The pregnant patient with SLE is at increased risk for fetal wastage, intrauterine growth retardation (IUGR), intrauterine fetal demise (IUFD), pregnancy-induced hypertension (PIH), and exacerbations of the lupus process. SLE is an autoimmune disease with tremendous implications for pregnancy. The diagnosis of SLE is based on criteria developed by The American Rheumatism Association. The recent identification of circulating antibodies associated with women who have lupus has led to some confusion. The circulating antibodies are associated with an increased risk of fetal wastage. However, those antibodies have been documented in women who do not have lupus. The diagnosis of SLE and pregnancy requires intensive obstetrical care. SLE may also affect the neonate, from skin lesions to complete heart block. This article describes the effects of SLE on the mother, pregnancy, and the neonate. PMID- 2202369 TI - Care of the pregnant woman with a pre-existing mental illness. AB - Pre-existing mental illness and pregnancy are not uncommon in todays obstetrical practice. The key to the nursing management of these women is identification and care planning. The purpose of this chapter is to give the clinician an overview of the major and minor mental disorders that may be seen in pregnant women today. The authors will discuss the nursing care of these women as well as aspects of psychotropic medication and pregnancy. PMID- 2202370 TI - Sickle cell disease and pregnancy. AB - Sickle cell disease combined with pregnancy provides a challenge for the caregivers. A thorough understanding of the normals of both pregnancy and sickle cell disease, along with continuing assessment and astute observational skills, will allow the attending nurses to provide appropriate care to the patient. A pregnancy, labor, and delivery with good outcome will make these extra efforts all worthwhile. PMID- 2202371 TI - Mitral stenosis in pregnancy: the nursing challenge. AB - Pregnancy in the patient with mitral stenosis may be complicated by pulmonary congestion/edema, atrial fibrillation, thromboembolic events, and intrauterine growth retardation. Combining both cardiac and obstetric principles with the bio/psycho/social focus of nursing is a challenge in the antepartum intrapartum and postpartum periods. PMID- 2202372 TI - Reproductive hazards in the workplace. AB - To ensure comprehensive health care delivery to individuals in their childbearing years, nurses must consider the impact of workplace hazards on human reproduction. A number of variables, including the changing role of women in society, economic issues, and unexplained adverse reproductive outcomes are indications for routine assessment of reproductive health hazards in the workplace. PMID- 2202373 TI - Anorexia nervosa and bulimia nervosa: chronic conditions affecting pregnancy. AB - Anorexia nervosa and bulimia nervosa primarily affect women who are in the childbearing years. While many anorectic patients are unable to ovulate second to the disruptions of normal body function associated with anorexia, there are still women who will ovulate and become pregnant. Bulimia nervosa may also disrupt the normal menstrual cycle if the disease is very severe. However, many bulimic patients will become pregnant. Both of these disease states cause a decrease in circulating plasma volume, fluid and electrolyte shifts, and other alterations that may increase the risk to a pregnancy and developing fetus. Severe disease states are associated with intrauterine fetal growth retardation (IUGR). The nursing care of the anorectic or bulimic patient who becomes pregnant is specialized and requires coordination between nursing, perinatology, and the psychiatric team, as well as support services including nutritionists. The nursing care of anorectic patients is difficult and requires an understanding of the complex psychological and physical pathophysiology of the disease. Bulimia nervosa also requires a complete understanding of the psychological and pathophysiology of the disease process. This article provides a review of the syndromes, risk factors, definitions of the disease states, and the nursing management of those patients experiencing a pregnancy complicated by the predisposing factors of anorexia nervosa, and/or bulimia nervosa. PMID- 2202374 TI - Cancer and pregnancy. AB - The diagnosis of cancer during or preceding pregnancy is not one that most perinatal nurses are familiar with. As a result of recent advances in management and improved survival rates, cancer is seen more often in childbearing women. A basic understanding of the most common pathologies along with recommended management strategies is essential in providing care for these patients. Nursing issues specific to different stages of maternity care are identified in addition to the need for involving other health professionals. PMID- 2202375 TI - Recombinant human erythropoietin (r-HuEPO): quality of life and other considerations. PMID- 2202376 TI - Localization of met-enkephalin like immunoreactivity in the glabrous skin of the cat rhinarium. AB - The presence of met-enkephalin like immunoreactivity (MEL IR) was investigated immunohisto-chemically in the glabrous skin of the cat rhinarium using the peroxidase-antiperoxidase Sternberger's method. Neither sensory corpuscles nor nerve bundles show MEL IR. MEL IR was found in the epidermal Merkel cells, as well as in Langerhans cells and/or melanocytes. In dermal papillae the reaction results positive in a number of cells which could be identified as Schwann or pigmentary cells. PMID- 2202377 TI - Roles of trace metals in transcriptional control of microbial secondary metabolism. AB - Secondary metabolism in bacteria and fungi requires a much narrower range of environmental concentrations of key trace metals than that permitted for primary metabolism. The cells acquire appropriate quantities of the key metals at the initiation of the shift from primary to secondary metabolism. Evidence suggests that these essential micronutrients participate in regulating the expression of genes responsible for synthesis of secondary metabolites and/or morphological alterations associated with cellular differentiation. PMID- 2202378 TI - Iron-regulated envelope proteins of mycobacteria grown in vitro and their occurrence in Mycobacterium avium and Mycobacterium leprae grown in vivo. AB - Several iron-regulated envelope proteins (IREPs), 11-180 kDa, have been detected in preparations of walls and membranes of Mycobacterium smegmatis, in an armadillo-derived mycobacterium (ADM) and in M. avium. The same sized proteins from M. vacae appeared under both iron-deficient and iron-sufficient growth conditions. Two larger proteins, of 240 and 250 kDa, appeared in the membranes of M. smegmatis and M. avium only when grown iron-sufficiently but were constitutively present in both ADM and M. vaccae. The IREPs from M. smegmatis were not induced under zinc-deficient growth conditions. Three of the four IREPs (14, 21 and 29 kDa) recognized in M. avium grown in vitro were also recovered from membrane fractions of the same strain grown in mice. In addition, these membranes contained both the high-molecular-mass proteins associated with iron sufficient growth conditions. Membranes of M. leprae, recovered from infected armadillos, showed the faint presence of a possible IREP at 29 kDa and wall preparations showed the presence of a 21-kDa protein. Membranes also contained the two larger proteins at 240 and 250 kDa. An explanation for the simultaneous occurrence of both low-iron-regulated and high-iron-regulated proteins is offered. PMID- 2202381 TI - Endogenous gene systems for the study of mutational specificity in mammalian cells. AB - Determination of the DNA sequence alterations produced by various mutagens is a prerequisite for understanding mechanisms of mutagenesis. With recent technical advances that permit rapid isolation of mutant alleles, the mammalian genome has become accessible to this type of analysis. Here we discuss the growing data base on mutational specificity in mammalian cells, with an emphasis on the information obtained from studies of two endogeneous genetic loci, aprt and hprt. PMID- 2202379 TI - Are myc proteins transcription factors? AB - Expression of the myc family of cellular proto-oncogenes is critical for determining the proliferative, differentiative, and oncogenic potential of a wide variety of cell types. Despite a large body of genetic and biochemical data indicating that myc proteins are located in the nucleus and can bind to nucleic acids, the mechanism by which these proteins exert their effects remains a mystery. The recent observation that myc proteins contain two structural domains previously identified in transcription factors and differentiation factors, the leucine zipper domain and the helix-loop-helix motif, supports the notion that these proteins directly regulate gene expression. In this review we consider the possible significance of these domains to myc function. PMID- 2202382 TI - Suramin: prototype of a new generation of antitumor compounds. AB - Suramin is a polysulfonated compound originally developed nearly 75 years ago for use as a trypanocidal agent. Recent studies indicate that suramin can also disrupt mammalian cell function, notably by blocking growth factor--receptor interactions and by inhibiting the activity of enzymes that are critical for cell growth and proliferation. These observations, together with the finding that clinically achievable concentrations of the drug are toxic to many human tumor cell lines, have prompted clinical investigations of suramin's efficacy as an antitumor agent. This review considers the possible mechanisms that may underlie suramin's cytotoxic effects and discusses ongoing clinical trials in cancer patients. PMID- 2202380 TI - Mucins in breast cancer: recent immunological advances. AB - Mucins are heavily glycosylated proteins that are produced in excessive amounts in breast cancers and other adenocarcinomas. These proteins are potent immunogens; indeed, most monoclonal antibodies raised against extracts of breast cancer cells or tumors are directed toward a single family of mucins. The anti mucin antibodies currently available are valuable diagnostic aids for detecting advanced stages of breast cancer. To improve the sensitivity of these antibodies so that they might be suitable for use in screening and early diagnosis, tumor imaging, and therapy of breast cancer, recent studies have focused on identifying the precise epitopes they recognize. PMID- 2202386 TI - Ultrasound in obstetrics. PMID- 2202387 TI - Vaginosonography in gynecology, early pregnancy, and gynecologic carcinoma screening. PMID- 2202385 TI - Determinants of gait in the elderly parkinsonian on maintenance levodopa/carbidopa therapy. AB - 1. We have used gait analysis to investigate the efficacy of maintenance therapy with a levodopa/carbidopa combination in patients with idiopathic Parkinsonism, who do not have overt fluctuations in control in relation to administration of medication. 2. Fourteen patients (aged 64 to 88 years) receiving maintenance therapy with levodopa and carbidopa (Sinemet Plus) entered a placebo-controlled, randomised cross-over study of the effect of omission of a morning dose of active treatment on distance/time parameters of gait. Measurements made 2, 4 and 6 h after the morning treatment were standardised by taking the pre-treatment measurement on that day as baseline. 3. The mean increase in stride length (7%) and decrease in double support time (20%) on active treatment were small but statistically significant (P less than 0.0001, in each case), there being no significant placebo effect on either gait parameter (P = 0.69 and 0.08 respectively). Neither active nor placebo treatments had any significant (P greater than 0.45 in each case) effect on the lying, standing or postural fall in mean arterial pressure, measurements being made in the same temporal relation to the treatments as was gait. 4. In a generalised linear model, after allowing for the effect (P less than 0.0001) of intrinsic variability in pre-treatment speed as well as for structure of the study, nature of treatment had an effect on stride length over the whole walk, significant at P = 0.002. 5. Pre-treatment postural fall in mean arterial pressure was nearly as significant (P = 0.003) as the nature of treatment in the context of such a model: the greater the fall, the greater the increment in stride length seen following active or placebo treatment. This was probably explained by an acquired tolerance to the fall as the day progressed. 6. The major determinant (P less than 0.0001) of the change in double support time over the whole walk, after allowing for the structure of the study, appeared to be the post treatment mean arterial standing blood pressure. The lower the pressure, the shorter the double support time, and hence, the greater the tendency to a hurried gait. 7. Nature of treatment, when added into the models described in summary points 5 and 6, had no significant effect (P greater than 0.25, in each case).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2202383 TI - Concerning antisense inhibition of the multiple drug resistance gene. AB - Recently, Vasanthakumar and Ahmed reported (Vasanthakumar, G.; Ahmed, N.K., Cancer Communications 1:225-232; 1989) a complete inhibition of the multiple drug resistance gene (MDR1) in the K562/III erythroleukemia cells, using a 15 bases long methylphosphonate oligodeoxynucleotide analog. The sequence used, however, contained three mismatches relative to the corresponding fragment of the human MDR1 gene and, hence, the results reported cannot at present be regarded as a classical antisense effect. We have made attempts to inhibit the expression of the MDR1 gene in MCF-7 human breast cancer cells selected for resistance to Adriamycin using phosphorothioate analogs of oligodeoxynucleotides. Studies with model 35S-labeled-phosphorothioates indicated poor uptake of the compounds into the cells; the radioactivity was located mainly in the soluble fraction (cytoplasm), but membranes and the nuclear fraction were also labeled. Unmodified oligodeoxynucleotides were toxic to the cells, whereas the phosphorothioates were not. The MDR1 inhibition with phosphorothioates was studied by measuring their effects on adriamycin toxicity and by immunocytochemical titration of P170. Elevation of adriamycin cytotoxicity consistent with a decreased drug resistance was observed with one antisense sequence, but the immunocytochemical assay indicated only slight inhibition of the synthesis of P170. In the wild type (drug sensitive) MCF-7 cells phosphorothioates decreased adriamycin toxicity in a sequence-independent manner. The results indicate that the effects of antisense oligodeoxynucleotides on cells are complex. Computer simulation of the secondary structure of MDR1 mRNA indicated not only extensive folding but, also, the presence of many regions not involved in intramolecular hybridization, which are of potential interest as targets for antisense oligodeoxynucleotides. PMID- 2202389 TI - Sonography of the gastrointestinal tract. PMID- 2202384 TI - Pharmacodynamic, pharmacokinetic and humoral effects of oral zabicipril, an angiotensin converting enzyme inhibitor in normotensive man. AB - 1. Zabicipril, S9650, a new angiotensin converting enzyme inhibitor, was administered to salt-replete, normotensive males in single doses of up to 10 mg. 2. The safety, tolerance and dose-response relationship with regard to inhibition of plasma ACE activity were characterised initially in an open, pilot, dose finding study in 12 subjects and further explored in a double-blind, parallel group, placebo controlled study in another 30 subjects. 3. The drug was generally well tolerated and produced no change in routine haematology or serum biochemistry tests. 4. Dose related (0.03 to 10 mg) inhibition of plasma converting-enzyme was observed, with 2.5 mg of zabicipril producing over 90% inhibition at 4 h and 60% at 24 h. 5. There were no significant changes in blood pressure or heart rate in normotensive subjects over the dose range studied. 6. A dose related rise in plasma renin activity and angiotensin I was observed. No dose related reduction in plasma aldosterone was observed. 7. These initial studies suggest that zabicipril is a well tolerated inhibitor of converting enzyme with near maximal inhibitory effect occurring at a dose of 2.5 mg. Further exploration of the dose range after single and multiple doses is indicated. PMID- 2202388 TI - Sonography in the genitourinary system. PMID- 2202392 TI - Color Doppler ultrasonography. PMID- 2202390 TI - Intraoperative and interventional ultrasound. PMID- 2202391 TI - Ultrasonographic evaluation of the carotid arteries. PMID- 2202394 TI - Magnetic resonance angiography, angiographic contrast media, and digital angiography. PMID- 2202393 TI - Cerebral arteriography. PMID- 2202395 TI - Biliary tract intervention. PMID- 2202396 TI - Renal tract intervention and genitourinary angiography. PMID- 2202397 TI - Obstetric intervention. PMID- 2202398 TI - Venography and venous intervention. PMID- 2202399 TI - Pulmonary angiography. PMID- 2202400 TI - Abdominal angiography and embolization. PMID- 2202401 TI - Biopsy, nonvascular balloon dilation, and percutaneous drainage. PMID- 2202403 TI - Angiography and interventional radiology. PMID- 2202402 TI - Diagnostic sonography. PMID- 2202404 TI - A multicentre, long-term evaluation of the safety and efficacy of ibuprofen syrup in children with juvenile chronic arthritis. AB - The safety, efficacy and acceptability of ibuprofen syrup were assessed in a multicentre controlled open study in children with juvenile chronic arthritis. Forty-six children aged 18 months to 13 years (mean 6.8 years) were studied. Dosage commenced at 10 mg/kg/day and increased to a maximum of 40 mg/kg/day depending on condition and individual disease control. Follow-up assessments of disease severity, active joint count and any side effects were made at each clinic visit, usually monthly or as often as deemed necessary by the physician. Thirty-nine children completed the minimum eight weeks treatment period, with average duration of treatment being eight months. Seven children did not complete the minimum required treatment period, of which four were lost to follow-up or non-complaint, two had suspected adverse reactions, and one had a taste complaint and nausea. Adverse reactions were predominantly gastrointestinal, but only one was severe enough for discontinuation from the study before the end of the protocol period. Two children had minimal benefit from treatment and were changed to other medication, 10 went into remission during the study period and four were lost to follow-up. Twenty-three children continued on ibuprofen syrup or tablets after the study period. This study demonstrates that ibuprofen is a well tolerated anti-inflammatory agent for children with juvenile chronic arthritis, and that the syrup form is particularly useful for small children who may not be able to swallow tablets. PMID- 2202405 TI - A randomised, double-blind study of mebeverine versus dicyclomine in the treatment of functional abdominal pain in young adults. PMID- 2202407 TI - Chlamydia trachomatis--clinical significance and strategies of intervention. AB - Chlamydia trachomatis is currently the most common sexually transmitted bacterial infection in the industrialized countries. In sexually active persons less than or equal to 25 years of age, prevalences up to 20% have been noted; urethritis/epididymitis in men and cervicitis/endometritis/salpingitis in women being the most common clinical expressions. Despite uncomplicated genital chlamydial infections often being asymptomatic or clinically indolent, sequelae to their complications are of importance in constituting the most common cause of acquired infertility in humans. Their commonness, high proportion of asymptomatic disease, and their serious postcomplication sequelae, make the genital chlamydial infections a major health problem; active search for genital chlamydial infections seems to be the most important means of intervention. PMID- 2202408 TI - Pelvic inflammatory disease. AB - Pelvic inflammatory disease (PID) and PID-related sequelae have risen to alarming proportions and are a major public health problem. During the last two decades, an epidemic of sexually transmitted diseases has led to an epidemic of PID that has now led to a secondary epidemic of tubal infertility and ectopic pregnancies. The direct and indirect economic consequences caused by PID to the community are enormous. The spectrum of clinical manifestations of PID is extremely broad, leading to major diagnostic problems in clinical practice. Although PID is the most preventable cause of tubal damage, PID and PID-related sequelae remain one of the most neglected areas in modern medicine. Prevention of PID should be the main goal of the appropriate diagnosis and treatment of lower genital tract infections. Only better understanding of the risk factors, microbial etiology, pathophysiology, immunopathology, and manifestation of PID can ultimately lead to improved therapeutic results and decrease in the current epidemic of acute, chronic, and late complications of PID. PMID- 2202406 TI - The epidemiology of sexually transmitted diseases in Africa and Latin America. AB - We review some aspects of the epidemiology of sexually transmitted diseases (STDs) in the developing countries of Africa and Latin America. Apart from their elevated prevalence, they are responsible for important morbidity in mother and child. Stillbirth, premature delivery, conjunctivitis, and respiratory tract morbidity of the neonate are frequently caused by STDs. Sequelae in adult women include pelvic inflammatory disease, ectopic pregnancy, and infertility. The emergence of antimicrobial resistance has complicated the picture in recent times. Genital ulcer disease is very common in developing countries, the most important being chancroid. Both continents are experiencing major epidemics of the acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection with different epidemiological characteristics than in the industrialized world. A link might exist between the high prevalence of STDs and the rapid heterosexual spread of HIV infection. PMID- 2202409 TI - Genital herpes--when and how to treat. AB - The link between genital ulcers and transmission of the human immunodeficiency virus highlights the need of prevention and treatment of genital herpes. Although a diversity of specific and unspecific drugs have been tested on effects toward herpes simplex virus types 1 and 2, only one antiviral drug, acyclovir, have proven safe and efficacious on some aspects of the disease. The drug has a marked effect on first episodes of herpes genitalis, but the effect on recurrences are less pronounced because viral replication is of shorter duration. Selection of patients for antiviral treatment involves considerations of immune status, the risk of neonatal transmission for pregnant women, and the severity of local and systemic symptoms, incidence of prodromal symptoms, and most importantly, recurrence rates, because this signals the psychological impact of the disease. The main goals of any herpes treatment--to eradicate latent infection in primary as well as recurrent disease--are not achieved by any known antiviral or immunomodulatory drug. PMID- 2202410 TI - Current status of podophyllotoxin for the treatment of genital warts. AB - An evolutionary process that began 50 years ago with a crude plant resin (podophyllum) has currently developed to the point where a fine chemical podophyllotoxin can be safely and effectively applied by patients for the treatment of external genital warts. In this brief review, the fundamental chemistry, pharmacology, and toxicology of podophyllotoxin will be reviewed, along with the sequence of clinical studies that resulted in the development of patient applied podophyllotoxin. PMID- 2202411 TI - Syphilis: test procedures and therapeutic strategies. AB - The diagnosis of syphilis is dependent mainly on serological tests. In primary syphilis there is a seronegative period when the diagnosis is dependent on demonstration of Treponema pallidum in lesional exudate. The most widely used screening tests for syphilis are the VDRL and the rapid plasma reagin (RPR) and for confirmation the fluorescent treponemal antibody (FTA) and the treponema pallidum hemagglutination (TPHA) tests. The nonvenereal treponematoses have the same serological response as in syphilis. For the diagnosis of neurosyphilis, the cerebrospinal fluid (CSF) parameters available are insufficient. The albumin quotient for estimation of the blood-brain barrier function is recommended as well as the IgG index, which is a measure of intrathecal immunoglobulin production. Treponemal antibodies in CSF have high sensitivity for neurosyphilis, although the specificity is low. Although penicillin has been used as first-line therapy in syphilis for more than 40 years, T pallidum has not shown any signs of decreased sensitivity. T pallidum is still one of the most penicillin-sensitive microorganisms known. The standard treatment is depot preparations (benzathine penicillin and procaine penicillin) giving a continuous low penicillinaemia. Treatment failures in early syphilis have been exceedingly rare, although in neurosyphilis there have been several reports indicating that low-dose therapy is insufficient. With recommended treatment regimens, treponemicidal levels of penicillin in CSF are not achieved. Failure of therapy and rapid progression to neurosyphilis has recently been reported in patients coinfected with human immunodeficiency virus (HIV). It has been proposed that neurosyphilis and patients coinfected with syphilis and HIV should be treated with high intravenous doses of benzylpenicillin. PMID- 2202412 TI - Diagnosis and management of acute genital ulcers in sexually active patients. AB - Sexually transmitted genital ulcer diseases include herpes simplex, chancroid, granuloma inguinale, lymphogranuloma venereum, and syphilis. Each of these infections has a characteristic clinical picture, but an accurate diagnosis usually requires the support of laboratory tests. The diagnosis will determine the appropriate therapy as well as sexual partner management. PMID- 2202413 TI - Human immunodeficiency virus infection: a survey with special emphasis on mucocutaneous manifestations. AB - Since the first reports of acquired immunodeficiency syndrome (AIDS) in 1981, many dermatological conditions have been reported to occur more commonly in people infected with human immunodeficiency virus (HIV). Acute HIV infection may first present as a skin eruption; the onset of immunosuppression after years of infection with HIV may be heralded by the development of various viral, fungal, bacterial, papulosquamous, or neoplastic eruptions. HIV disease often presents first to dermatologists who must be aware of subtle presentations and the possibility of underlying HIV infection--as well as alert to danger signals that indicate the need for urgent treatment or referral. PMID- 2202415 TI - Sexually transmitted diseases in five continents. PMID- 2202414 TI - Sexually transmitted diseases and enteric infections in the male homosexual population. AB - There are certain special considerations in the management of sexually transmitted diseases (STDs) in homosexual men, with the impact of human immunodeficiency virus (HIV) infection on the presentation, diagnosis, and management of certain STDs just becoming apparent recently. Rectal and pharyngeal gonorrhea are usually asymptomatic and also more difficult to treat. The serological diagnosis of syphillis may be unreliable in acquired immunodeficiency syndrome (AIDS) patients, and HIV-seropositive homosexual men may be at risk of accelerated progression to neurosyphilis, despite treatment with benzathine penicillin. Chlamydia trachomatis is infrequently detected in patients with proctitis so therapy should be directed only at culture-positive cases. Herpes simplex is usually severe and persistent in immunosuppressed patients and may be further complicated by the development of acyclovir-resistance. Concurrent HIV infection may be associated with increased infectivity of homosexual chronic hepatitis B carriers, but milder hepatic injury and reduced efficacy of hepatitis B vaccines and immodulatory or antiviral agents. Although there is some concern regarding the possibility of increased risk of anal cancer in homosexual men, conservative management of human papilloma-virus-associated conditions is advised. The carriage of Entamoeba histolytica in this group is rarely associated with any deleterious effects and treatment should be directed only at symptomatic patients in whom other enteric pathogens have been excluded. PMID- 2202416 TI - The epidemiology of sexually transmitted diseases in the West. AB - Sexually transmitted diseases (STDs) continue to increase in number throughout the world, as do the number of agents that are spread by the sexual route; the most recent new agent is the human immunodeficiency virus. Most countries do not have adequate control programs for STDs or training programs for physicians and nurses designated to look after patients. The diseases are associated with considerable morbidity and recently, with the advent of the acquired immunodeficiency syndrome, with considerable mortality. PMID- 2202417 TI - Salmonella control by immunization of animals. PMID- 2202419 TI - Is apocrine differentiation in breast carcinoma of prognostic significance? AB - Apocrine differentiation in human breast cancers has been assessed using immunohistochemistry to detect zinc alpha 2 glycoprotein and the findings related to standard prognostic factors, disease free interval (DFI) and survival in 145 women with early breast cancer. Breast tumour samples from women with a minimum follow-up of 5 years were assessed. Routinely fixed and processed tissue was used throughout. Sixty-six (45%) tumours did not stain with the antibody. Fifty-two (36%) exhibited positive apocrine staining while for 27 (19%) only a few cells were reactive. The presence of apocrine differentiation was unrelated to lymph node status, menstrual status, tumour grade or size, oestrogen receptor (E2R) or progesterone receptor status. However, patients whose tumours exhibited apocrine staining had a shorter disease-free interval (DFI) (P = 0.03) and survival (P = 0.03). A Cox's multiple regression analysis of the data found that the presence of staining added significantly (P = 0.047) to the predictive value of node status (P = 0.0001), menstrual status (P = 0.0001), tumour size (P = 0.0026) and E2R status (P = 0.0014) for patient survival. The other seven prognostic factors tested did not reach significance and were rejected from the model. Apocrine differentiation in breast cancer appears to be an independent predictor of poor prognosis tumours. PMID- 2202418 TI - Discordant results between radioligand and immunohistochemical assays for steroid receptors in breast carcinoma. AB - Surgical biopsy specimens of 179 breast carcinoma were studied by steroid-binding and immunohistochemical assays or oestrogen and progesterone receptors (ER, PR) in order to explore reasons for discordant results between the two assay types. Receptor statuses in 18% of ER assays and 30% of PR assays were in disagreement. Immunohistochemistry-positive steroid-binding-negative status predominated among the discordant ER assays, while the discordant PR assays displayed the opposite situation. In discordant assays receptor concentration was significantly more often close to the cut-off (10-50 fmol mg-1) than in the concordant ones. Low binding affinity (high Kd) was also significantly associated with disagreeing assay results. These observations clearly indicate that immunohistochemical ER and PR assays measure high-affinity binding components (i.e. type I receptors) in steroid-binding assays. ER but not PR assays in premenopausal women disagreed more often than those in post-menopausal women. Such factors as histological type, specimen size in steroid-binding assay, grade of malignancy and tumour necrosis were statistically unrelated to agreement or disagreement of receptor assays. PMID- 2202420 TI - Childhood cancer after prenatal exposure to diagnostic X-ray examinations in Britain. AB - Detailed data were provided by the Oxford Survey of Childhood Cancer OSCC on deaths from childhood cancer in Britain after irradiation of the fetus during diagnostic radiology of the mother. In each age group at death, 0-5, 6-9 and 10 15 years, excess cancer deaths decreased suddenly for births in and after 1958. A major factor was concerted action initiated in 1956 to reduce radiation exposure of fetal gonads for fear of genetic hazards. Dose reduction was achieved during 1957 and early 1958 by reducing the rising rate of obstetric radiography and by virtually abandoning pelvimetry as that had been understood. In the 1970s the rate of X-raying increased again and so did cancer risk but not significantly. Direct evidence that diagnostic X-rays can cause childhood cancer is the similar excess rate per X-ray in twins and singleton births when X-raying rate is 5-6 times higher in twins. In the past a dose-response for cancer in OSCC data based on number of films per X-ray examination was taken to be evidence for causation but dose per film varies with kind of X-ray examination. Fixed values for dose per film were mistakenly assumed by UNSCEAR (1972) and used by it and others when deriving risk co-efficients. In updated OSCC data cancer risk is independent of film number. The odds ratio for childhood cancer deaths after X-raying in birth years 1958-61 (1.23 with 95% confidence intervals CI 1.04-1.48) and the mean fetal whole body dose from obstetric radiography in 1958 (0.6 cGy) can each be derived from nationwide surveys in Britain. The corresponding risk coefficient for irradiation in the third trimester for childhood cancer deaths at ages 0-15 years = 4-5 x 10(-4) per cGy fetal whole body dose (95% CI 0.8-9.5 x 10(-4) per cGy). It is the same for cancer incidence and mortality. A lower risk in bomb survivors exposed in utero is not incompatible since its CI are wide. There is no dependable evidence that radiosensitivity is greater in early pregnancy. A significantly raised cancer rate after diagnostic X-raying supports the hypothesis that carcinogenesis by ionising radiation has no threshold. PMID- 2202421 TI - Purification and characterisation of soluble tumour haemolytic factor isolated from oncogene transformed fibroblasts. AB - Numerous studies have shown that intact cancer cells and cell extracts have the capacity to lyse erythrocytes in vitro. The transformation of NIH-3T3 fibroblasts by ras oncogenes has recently been demonstrated to result in tumour cells releasing a haemolytic factor. The purpose of this study has been to purify and further characterise the soluble tumour haemolytic factor (sTHF) produced by mouse fibroblasts transformed by T24 human bladder cancer DNA and by the cloned Harvey murine sarcoma viral oncogene. To this end, transformed fibroblasts were cultivated in serum-free medium. The cell-free supernatant was treated with ammonium sulphate and the precipitate achieved at 60-100% saturation was dialysed and applied to a gel filtration column. A haemolytic factor was eluted with an Mr between 65,000 and 75,000. Zinc chelate and strong anion exchange column chromatography resulted in greater than 3,000-fold enrichment of sTHF. SDS-PAGE of sTHF resulted in a single protein band of 66,000 Da. Soluble THF had no immunological cross-reactivity with known cytokines produced by lymphocytes and macrophages. The pathophysiological role of sTHF in cancer remains to be determined. PMID- 2202422 TI - Contrast-enhanced magnetic resonance imaging of the abdomen and pelvis. AB - Contrast media in magnetic resonance imaging (MRI) of the abdomen and pelvis are applied for various purposes; different substances and forms of application must be distinguished. Oral contrast agents are primarily used to enhance the discrimination of the intestine from the other organs and from pathological lesions. Clinical studies of i.v. contrast agents focus on two substances: gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) and superparamagnetic iron oxide. Whereas dynamic Gd-DTPA-enhanced MRI improves the differential diagnosis of focal hepatic lesions, iron oxide is a promising agent for increasing the sensitivity of MRI in the detection of hepatic and splenic tumors. Dynamic Gd-DTPA-enhanced MRI of the kidney allows functional assessment of this organ; good demarcation of kidney tumors is only achieved during the early phase of a dynamic examination. In the assessment of adrenal lesions, dynamic Gd-DTPA enhanced MRI permits better differentiation of adenoma from malignancy. Intravenous Gd-DTPA also appears to be useful in the staging of urinary bladder tumors to distinguish between superficial and infiltrating tumors. Although offering no major diagnostic advantage in the staging of cervical carcinomas, Gd DTPA-enhanced MRI improves the discrimination of necrotic tumor portions of endometrial carcinoma and allows good differentiation of this lesion from fluid retained in the uterine cavity. Studies of new contrast agents for MRI of the abdomen, which have so far only been investigated in animal experiments, focus on liver imaging. These substance include hepatobiliary agents, Gd-DTPA-containing liposomes, and paramagnetic macromolecules. PMID- 2202424 TI - Magnetic resonance contrast media: principles and progress. AB - The principles and current state of the art for magnetic resonance (MR) imaging contrast media are reviewed. All forms of paramagnetic and superparamagnetic MR contrast agents are covered, including discussions of their effect on MR relaxation and image intensity as well as their chemical and physiological properties. PMID- 2202423 TI - Magnetic resonance contrast agents in the evaluation of the musculoskeletal system. PMID- 2202425 TI - The role of gadolinium-diethylenetriaminepentaacetic acid in the evaluation of the central nervous system. PMID- 2202426 TI - Obliterative bronchiolitis and alveolitis associated with sulphamethoxypyridazine (Lederkyn) therapy for linear IgA disease of adults. PMID- 2202428 TI - Ciprofloxacin-induced photosensitivity: in vitro and in vivo studies. AB - Ciprofloxacin is one of the new series of broad-spectrum antibiotic quinolones, chemically related to nalidixic acid and which may, therefore, induce photosensitization of human skin. Three in vitro tests for phototoxicity: the destruction of histidine, killing of mouse peritoneal macrophages and inhibition of PHA-stimulated DNA synthesis in human lymphocytes have demonstrated this photosensitizing potential with UVA irradiation at an order of magnitude lower than that for nalidixic acid. The Candida albicans test and photohaemolysis were negative. Controlled irradiation monochromator phototesting of 12 subjects, before, during and after taking ciprofloxacin showed subclinical photosensitivity with significantly lowered minimal 24 h erythema doses at 335 +/- 30 nm, 365 +/- 30 nm and 400 +/- 30 nm but not at 305 +/- 5 nm or above 400 +/- 30 nm. PMID- 2202427 TI - Association of EGF receptor expression with proliferating cells and of ras p21 expression with differentiating cells in various skin tumours. AB - The localization of DNA replicating cells, epidermal growth factor (EGF) receptor expressing cells and ras oncogene product p21 (p-21ras) positive cells were examined in various skin tumours to elucidate the role of EGF receptor and p21ras in the epidermis. Normal skin, keratoacanthoma (KA), solar keratosis (SK), Bowen's disease (BD), squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and extramammary Paget's disease (PD) were studied. EGF receptors were seen in proliferating layers, where DNA replicating cells localize, but p21ras was found in the more differentiated layers. We conclude that EGF receptor expression is closely associated with cellular proliferation, but p21ras may play a role in the differentiation of cells in various skin tumours. PMID- 2202429 TI - Psoriasis consultation audit: a two-centre study. AB - The adequacy of hospital note-keeping in 100 patients presenting with psoriasis at two teaching hospitals has been assessed. The criteria used were defined in consultation with a peer group of 60 British dermatologists. The pattern of record keeping was similar in both centres. Where differences existed between consultant (C) and non-consultant (J) staff, non-consultant staff completed the records more fully. There were differences between centres in the recording of patients' symptoms and disability, psoriasis type, and in the number of visits before discharge to general practitioners care. Both centres had a poor record of communication to general practitioners following patient default from the clinic. In both centres, the patient had only a one in 8 chance of subsequently being seen by a consultant if at the first visit they had been seen by a non consultant. This simple case-note audit has highlighted the similarity of practice in the two centres and has resulted in practical improvements in record keeping. PMID- 2202430 TI - Has in-vitro fertilization made salpingostomy obsolete? PMID- 2202431 TI - The results of tubal surgery in the treatment of infertility in two non specialist hospitals. AB - The results of surgery for tubal damage, other than reversal of sterilization, were studied in two large hospitals. This is the first recent study from centres claiming no special expertise in this surgery. An unusually high follow-up rate was obtained. The term pregnancy rate for patients operated on for bilateral distal tubal occlusion was 4%. The success rate is lower than the lowest reported, overall success rates for each cycle of in vitro fertilization (IVF) and very much lower than cumulative term pregnancy rates for tubal surgery reported by most other authors. Patients with distal tubal occlusion but minimal adhesions had the best prognosis. Our results suggest that, provided in vitro fertilization is available, only those patients with good prognostic factors should undergo tubal surgery. These represent the minority of all patients with non-iatrogenic tubal blockage. PMID- 2202432 TI - Uterine size and endometrial thickness and the significance of cystic ovaries in women with pelvic pain due to congestion. AB - In a group of 55 women with chronic pain due to pelvic congestion measurement by ultrasound revealed they had a larger uterus and thicker endometrium as compared with a group of normal women matched for age, parity and the presence of polycystic ovaries found on ultrasound scanning. Many women with pelvic congestion (56%) were found on ultrasound to have cystic changes in their ovaries which ranged from a classic polycystic pattern to the appearance of clusters of 4 6 cysts in bilaterally enlarged ovaries. It is suggested that uterine enlargement and thickening of the endometrium are caused by oestrogen, either from the effects on the target organs of an increased concentration or of hypersensitivity to oestrogen. PMID- 2202433 TI - Simultaneous intrauterine and cervical pregnancies after in vitro fertilization and embryo transfer in a patient with a history of a previous cervical pregnancy. Case report. PMID- 2202434 TI - Exfoliation syndrome. PMID- 2202435 TI - Stabilisation of refraction following extracapsular cataract extraction. AB - Regular serial refraction was used to determine the rate of stabilisation of refraction following routine extracapsular cataract surgery in 85 eyes. Patients were divided into four groups depending on wound closure technique: limbal section closed by interrupted 8-0 virgin silk, 9-0 polydioxanone or 10-0 nylon sutures, and corneal section closed by continuous 10-0 nylon suture. Stabilisation of refraction, sufficient to prescribe satisfactory glasses, occurred at three months except in the interrupted 10-0 nylon group, when stabilisation was delayed to between four and five months. The factors affecting stabilisation and the causes of the differences observed are discussed. PMID- 2202436 TI - Neuro-ophthalmology. PMID- 2202437 TI - Aneurysmal bone cyst of the sphenoid with orbital involvement. AB - We present a case of aneurysmal bone cyst involving the roof of the orbit and sphenoid bone, with plain film, computed tomography, and magnetic resonance imaging findings. The natural history and treatment depend on the presence of associated abnormalities such as fibrous dysplasia or a giant cell tumour. In this case the lesion was solitary and was successfully removed, so that possible complications from radiotherapy were avoided. PMID- 2202438 TI - Distributed parallel processing in the vertical vestibulo-ocular reflex: learning networks compared to tensor theory. AB - The vestibulo-ocular reflex (VOR) is capable of producing compensatory eye movements in three dimensions. It utilizes the head rotational velocity signals from the semicircular canals to control the contractions of the extraocular muscles. Since canal and muscle coordinate frames are not orthogonal and differ from one another, a sensorimotor transformation must be produced by the VOR neural network. Tensor theory has been used to construct a linear transformation that can model the three-dimensional behavior of the VOR. But tensor theory does not take the distributed, redundant nature of the VOR neural network into account. It suggests that the neurons subserving the VOR, such as vestibular nucleus neurons, should have specific sensitivity-vectors. Actual data, however, are not in accord. Data from the cat show that the sensitivity-vectors of vestibular nucleus neurons, rather than aligning with any specific vectors, are dispersed widely. As an alternative to tensor theory, we modeled the vertical VOR as a three-layered neural network programmed using the back-propagation learning algorithm. Units in mature networks had divergent sensitivity-vectors which resembled those of actual vestibular nucleus neurons in the cat. This similarity suggests that the VOR sensorimotor transformation may be represented redundantly rather than uniquely. The results demonstrate how vestibular nucleus neurons can encode the VOR sensorimotor transformation in a distributed manner. PMID- 2202439 TI - [Pygomelus. A single monster or a double monster?]. AB - With an anatomical case and a clinical case, the authors describe the pygomelus, a very rare monstruosity. Legend and reality are often mixed in the description of literature. It is difficult to classify this monstruosity either in the simple monster or in the twin monsters. PMID- 2202440 TI - Biochemical neonatal screening. PMID- 2202441 TI - Thiazides in the 1990s. PMID- 2202442 TI - The mental health of Asians in Britain. PMID- 2202443 TI - Atherosclerotic renovascular disease. PMID- 2202446 TI - ABC of major trauma. Thoracic trauma--II. PMID- 2202444 TI - Oocyte donation. PMID- 2202445 TI - The effectiveness of two smoking cessation programmes for use in general practice: a randomised clinical trial. AB - OBJECTIVE: To evaluate a structured, behavioural change, smoking cessation intervention designed for use within general practice. DESIGN: Randomised controlled clinical trial. SETTING: General practices in Newcastle, Australia. PATIENTS: 311 Patients identified as smokers by a screening question were enrolled in the study. Of these, 101 were assigned to a structured behavioural change programme, 104 to a simple advice programme adapted from previous research, and 106 to a control group. No significant differences were found between groups for demographic and smoking related variables before the study. INTERVENTIONS: Patients in the simple advice group received a brief statement of advice from the general practitioner as well as three pamphlets; those in the structured intervention group were given strategies which included attitude and behavioural change programmes as well as techniques to aid compliance. The amount of smoking in all groups was assessed by self reports with validation by measurement of salivary cotinine concentrations. MAIN OUTCOME MEASURE: Significant increase in cessation rates. CONCLUSIONS: Significant differences between controls and the structured behavioural change group were found at the one month follow up, but only for self reported abstinence. The simple advice programme did not produce any significant differences over the control group. General practitioner evaluation of the structured programme highlighted difficulties in relation to the duration of the intervention. Overall the structured programme in its present form did not appear to be an effective programme for use within general practice. PMID- 2202447 TI - ABC of major trauma. Trauma of the spine and spinal cord--II. PMID- 2202448 TI - HTLV-I infection in Britain. PMID- 2202449 TI - Leukaemia and cancer chemotherapy. PMID- 2202450 TI - Prognosis of abdominal aortic aneurysm. PMID- 2202452 TI - ABC of major trauma. Abdominal trauma. PMID- 2202451 TI - Short term linear growth in asthmatic children during treatment with prednisolone. AB - OBJECTIVE: To see whether small daily doses of prednisolone have any adverse effect on short term linear growth in children with mild asthma. DESIGN: Double blind, random order crossover trial of two dosages of prednisolone. During run in and washout periods patients were given placebo. All treatment periods were of two weeks' duration. SETTING: Outpatient clinic referrals in a secondary referral centre. PATIENTS: 14 Children (10 boys) aged 7-11 years with normal growth velocity during the previous year, no signs of puberty, and no history of receiving systemic or topical steroids during the two months before the study. One child was excluded because his pulmonary function deteriorated and another was withdrawn because of varicella. INTERVENTIONS: 2.5 and 5.0 mg prednisolone daily given in divided dosage in the morning and evening. MAIN OUTCOME MEASURE: Growth of the lower leg as measured twice a week by knemometry. RESULTS: A significant reduction in mean growth velocity of the lower leg occurred in both prednisolone treatment periods. The mean difference between the run in period and the treatment period with 2.5 mg prednisolone daily was 0.63 mm/week (95% confidence interval 0.47 to 0.80 mm/week) and between the run in period and the treatment period with 5.0 mg prednisolone daily 0.57 mm/week (0.38 to 0.77 mm/week). CONCLUSION: Small daily doses of prednisolone suppress short term linear growth in children with mild asthma. The clinical relevance of this finding needs further study. PMID- 2202453 TI - Selecting patients for cerebral angiography before carotid endarterectomy. PMID- 2202455 TI - Liver function tests. PMID- 2202454 TI - Plasma concentrations of tryptophan and dieting. PMID- 2202457 TI - The ghost of Edwin Chadwick. PMID- 2202456 TI - Is antenatal selection for spina bifida possible? PMID- 2202459 TI - ABC of major trauma. Management of severe burns. PMID- 2202458 TI - Double blind placebo controlled trial of pulse treatment with methylprednisolone combined with disease modifying drugs in rheumatoid arthritis. AB - OBJECTIVE: To assess whether monthly treatment with intravenous methylprednisolone enhances or accelerates the effect of disease modifying drugs in patients with rheumatoid arthritis. DESIGN: A 12 month double blind, placebo controlled, multicentre trial in which patients with active rheumatoid arthritis were randomly allocated to receive pulses of either methylprednisolone or saline every four weeks for six months. At the start of the pulse treatment all patients were started on penicillamine or azathioprine. SETTING: Four rheumatology departments in Denmark. PATIENTS: 97 Patients (71 women, 26 men) aged 23-84 (mean 60) who had active rheumatoid arthritis of at least four weeks' duration despite treatment with non-steroidal anti-inflammatory drugs. MAIN OUTCOME MEASURES: Monthly clinical recording of morning stiffness, number of tender and swollen joints, blinded observers' evaluation of therapeutic effect, and patients' self assessed condition. Concomitant laboratory measurements of erythrocyte sedimentation rate and concentrations of C reactive protein and haemoglobin. Radiography to determine the number of erosions at the start of treatment and after 12 months. RESULTS: 57 Patients completed the trial, taking the same disease modifying drug throughout. Evaluation four weeks after each pulse treatment and at 12 month follow up showed no significant differences between the methylprednisolone and placebo groups in any of the clinical or laboratory variables. Radiography showed the same degree of progression of erosions in both groups. Evaluation of the total data on 97 patients and on the 57 who completed the trial showed the same lack of significance between the treatment groups. CONCLUSIONS: Intravenous pulse treatment with steroids can be recommended only for rapid temporary relief of flares of disease in patients with rheumatoid arthritis. The response is short lived. Repeated pulses of methylprednisolone at four week intervals do not improve the results of treatment with drugs that induce remission such as penicillamine and azathioprine. PMID- 2202460 TI - Management of acute graft-versus-host disease. AB - Current graft-versus-host disease (GVHD) prophylaxis is not uniformly successful. Since the development of GVHD has a profound impact on transplant success, treatment is required. The mainstay of therapy has been glucocorticoids (steroids), along with anti-thymocyte globulin, cyclosporine, monoclonal antibodies, and aggressive supportive care, resulting in response rates of 30 50%, dependent upon severity of the disease, type of transplant, underlying diagnosis, prophylaxis given and other factors. Dose intensification or combinations of agents may increase response rates (60-80%), however, without necessarily improving survival, due to intervening complications. Nevertheless, patients with complete responses have a higher probability of survival, and a subgroup of patients will not develop chronic GVHD. As our understanding of cell recruitment, cell interactions and cytokine networks improves, new strategies are likely to be developed. The sequential use of antibodies directed at different cell populations or cytokines, along with anti-inflammatory measures, may be helpful. Prevention of GVHD has to remain our objective; however, efforts at therapy must continue until that goal is achieved. PMID- 2202461 TI - Cyclosporine-induced graft-versus-host disease following autologous bone marrow transplantation in acute myeloid leukaemia. AB - Cyclosporine was used to induce graft-versus-host disease (GVHD) in patients with acute myeloid leukaemia (AML) receiving autologous bone marrow transplantation (ABMT). Nine consecutive patients with AML in remission were conditioned with either busulphan and cyclophosphamide or melphalan and total body irradiation (TBI) followed by ABMT. Cyclosporine, 1 mg/kg daily from days 1-28 was administered intravenously in four patients and orally in five. Acute GVHD of the skin, confirmed by histological and immunological criteria occurred in three patients, 4-28 days after ABMT and lasted 8-18 days. Incidence and severity of GVHD were independent of cyclosporine levels. Three patients subsequently relapsed, of whom two had had evidence of GVHD. All of these patients were in second remission at time of graft, and therefore poor risk. The potential of cyclosporine to induce GVHD in the AML autograft setting is demonstrated, although the significance of this observation in terms of an antileukaemia effect needs clarification. PMID- 2202463 TI - Graft-versus-leukemia activity after T-cell depletion using counterflow centrifugation. PMID- 2202464 TI - GM-CSF in combination with cytotoxic chemotherapy in AML patients. PMID- 2202462 TI - Bone marrow transplantation for acute lymphocytic leukemia utilizing total body irradiation followed by high doses of cytosine arabinoside: lack of superiority over cyclophosphamide-containing conditioning regimens. AB - The efficacy of a pre-bone marrow transplantation (BMT) preparative regimen consisting of single, high dose rate total body irradiation followed by 12 courses of high dose cytosine arabinoside (Ara-C) over 6 days with allogeneic or autologous rescue was studied in 68 consecutive patients with poor risk acute lymphocytic leukemia (ALL). Toxicity associated with the above preparative regimen included conjunctivitis in the majority of patients, severe gastrointestinal symptoms in seven patients (10%), skin desquamation in four patients (6%), and interstitial pneumonitis of unknown etiology in two patients (3%). One patient died from a 'capillary leak' syndrome that may have been attributable to Ara-C toxicity. With a follow-up of 1.1-4.3 years, the estimated survival is 21% (95% confidence interval, 10-32%), with a disease-free survival of 18% (8-28%) and an estimated relapse rate of 75% (62-88%) at 3 years. These results are not significantly different from overall outcome in 105 patients treated previously at this same institution with cyclophosphamide-containing preparative regimens (31% (22-40%) estimated survival, 29% (20-38%) disease-free survival, and an estimated relapse rate of 63% (52-74%) at 3 years), especially when results are stratified based on allogeneic versus autologous BMTs. Although efficacious for a minority of patients with poor risk ALL, a pre-BMT preparative regimen consisting of total body irradiation followed by high doses of Ara-C did not improve long-term survival over more conventional preparative regimens consisting of cyclophosphamide and total body irradiation. Future strategies may need to investigate novel approaches for reducing leukemic relapse rates in patients with ALL undergoing bone marrow transplantation. PMID- 2202465 TI - Recombinant human GM-CSF following chemotherapy in high-risk AML. AB - Chemotherapy (CT) induced critical neutropenia remains a major dose limiting problem in acute leukemias. In order to reduce the phase of risk we gave recombinant human GM-CSF to 30 patients at high risk of early death with acute myeloid leukemia (AML). 19 patients with untreated AML and 1 patient with AML late relapse were 65+ years of age and were treated for CT by the TAD9 regimen. 10 patients at all ages had AML early or second relapse and received S-HAM CT. Starting on day 4 after CT GM-CSF 250 micrograms/m2/d was given by continuous i.v. infusion until neutrophils recovered. GM-CSF reduced the median recovery time of neutrophils by 4 days in the TAD9 and 9 days in the S-HAM CT group when compared to controls. After the CT induced aplasia 3 patients with AML showed a regrowth of their blasts which after the stop of GM-CSF was reversible in 1 patient and unaffectedly continued in 2 patients. 57% of patients attained a complete remission, and the median age of the responders was 65 (34-84) years. Remission duration was not found to be reduced. Thus, GM-CSF reduces CT toxicity with a low risk of promoting the disease and may allow more effective antileukemic treatment. PMID- 2202467 TI - Intensive chemotherapy versus allogeneic bone marrow transplantation in first remission acute myeloid leukemia. AB - At present, using the most contemporary management techniques, it would appear that allogeneic bone marrow transplantation and intensive chemotherapy offer a roughly equivalent potential for curing adult patients with AML in first remission. Each form of treatment has drawbacks--the limited eligibility and continued high rate of early death associated with the allogeneic transplant procedure and the significantly greater likelihood of relapse, as well as the risk for drug-induced, life-threatening toxicities observed following the administration of chemotherapy. Future efforts should be directed at improving each of these treatment techniques, perhaps through kinetic synchronization of leukemic cells by hematopoietic growth factors to make chemotherapy more potent and by better understanding and then harnessing the "graft-versus-leukemia" effect which appears so instrumental in reducing the relapse rate following allografting. PMID- 2202466 TI - Analytical approaches to detection and characterization of disease-linked chromosome aberrations. AB - Flow karyotyping and FISH with chromosome specific or disease-locus-specific probes are powerful adjuncts to conventional cytogenetic analysis. Flow karyotyping is well suited to quantitative analysis of DNA content changes that occur during structural rearrangement. FISH with probes for repeated sequences allows ready detection of aneuploidy in interphase cells. FISH with whole chromosome composite probes to metaphase spreads facilitates detection of subtle structural changes and allows detection of structural aberrations that occur at frequencies as low as 10(-3). FISH with locus-specific probes facilitates diagnosis of specific genetic diseases, allows phenotype-genotype correlation on a cell-by-cell basis and may be developed into a sensitive method for detection of residual disease. PMID- 2202468 TI - Autologous bone marrow transplantation in first remission AML--its relative value. PMID- 2202469 TI - Allogeneic and autologous bone marrow transplantation for patients with acute non lymphoblastic leukemia in first complete remission. The Genoa experience on 119 patients. PMID- 2202470 TI - Relative value of allogeneic BMT, autologous BMT and intensive chemotherapy during the first complete remission (CR) of acute myelogenous leukemia (AML). An interim analysis of the AML8 EORTC-GIMEMA protocol. PMID- 2202472 TI - A comparison of the outcome of ABMT in first remission acute myeloid and lymphoblastic leukemia in a single centre. PMID- 2202471 TI - Autograft to eliminate minimal residual disease in AML in first remission--update on the Glasgow experience. PMID- 2202473 TI - Minimal residual disease: lessons to be learned from malignant lymphoma. PMID- 2202474 TI - Autologous marrow transplantation in acute lymphoblastic leukemia: control of residual disease with mafosfamide and induction of syngeneic GVHD with cyclosporin. The Italian Mafosfamide Study Group. PMID- 2202475 TI - Premature chromosome condensation in the study of minimal residual disease. PMID- 2202476 TI - Treatment of residual disease in acute leukemia patients with recombinant interleukin 2 (IL2): clinical and biological findings. PMID- 2202477 TI - Pretreatment with rh-GMCSF, but not rh-IL3, enhances PAF-induced eosinophil accumulation in guinea-pig airways. AB - Intraperitoneal injections of recombinant human granulocyte-macrophage colony stimulating factor (rh-GMCSF, 50 micrograms/kg-1 daily) or interleukin-3 (rh-IL3, 50 micrograms kg-1 daily) for two days, induced an increase in the percentage of bone marrow and pulmonary airway eosinophils in the guinea-pig. In addition, rh IL3-treated animals exhibited an increase (21%) in blood neutrophils. Exposure of guinea-pigs to an aerosol of platelet activating factor (PAF) gives rise to a selective pulmonary eosinophil accumulation, maximal at 48 h. The eosinophilic response to PAF was significantly enhanced in rh-GMCSF-treated guinea-pigs but was suppressed in rh-IL3-treated animals. PMID- 2202478 TI - Influence of capsaicin-sensitive afferent neurones on the acid secretory responses of the rat stomach in vivo. AB - 1. The influence of capsaicin-sensitive afferent neurones in modulating acid secretory responses has been investigated in the continuously perfused stomach of the anaesthetized rat. 2. Ablation of primary afferent neurones, after systemic neonatal pretreatment with high doses of capsaicin, did not modify acid responses to direct stimuli of the oxyntic cell with histamine (5 mg kg-1), pentagastrin (20 micrograms kg-1) or carbachol (4 micrograms kg-1). 3. Acid responses to hypoglycaemia induced by insulin (0.3 iu kg-1) were not influenced by systemic capsaicin pretreatment or by acute coeliac ganglionectomy. Vagotomy abolished this secretory response. 4. The increase in acid output induced by gastric distension (20 cmH2O) was abolished by systemic neonatal capsaicin pretreatment. Likewise, vagotomy and acute coeliac ganglionectomy eliminated this secretory response. 5. Acute intragastric infusion with high doses of capsaicin inhibited the acid responses to distension but failed to modify the increase in acid output induced by insulin. 6. Local application (7-14 days before) of capsaicin to the coeliac ganglion abolished the acid response to gastric distension. This lack of secretory response was not the result of a nonspecific destruction of the ganglion, since changes in intragastric pressure after electrical stimulation of the coeliac ganglion were unaffected by such treatment. 7. These observations indicate that peripheral capsaicin-sensitive sensory neurones, located both in the gastric mucosa and in the coeliac ganglion, play a physiological role in the acid secretory responses to gastric distension. PMID- 2202479 TI - Urinary tract infection in paediatrics: the role of diagnostic imaging. PMID- 2202481 TI - Primary osteosarcoma of the uterus. PMID- 2202480 TI - Evaluation of response to chemotherapy of human cystic echinococcosis. AB - Fifty-five patients with echinococcosis were treated with mebendazole (30) and albendazole (25). To determine changes in cyst morphology and to evaluate the varying degree of response, progress during follow-up was shown by radiography, computerized tomography and ultrasonography. Persistence of cysts without any change in the morphology and cyst enlargement were taken as criteria for unsuccessful treatment. Development of echogenic foci and increase in density of cyst fluid were considered as a therapeutic effect. Changes in cyst wall such as thickening and deposition of calcium and detachment of the cyst membrane may also indicate response. An essential criterion, for a positive drug effect, was cyst size reduction as well as shape deformation. However, the most convincing and reliable criterion was the complete disappearance of hydatid cysts. Comparative assessment of the therapeutic effect of the two drugs favoured albendazole. PMID- 2202482 TI - Quality assurance of ultrasound test objects. PMID- 2202483 TI - Urinary diversion. AB - Although the ileal conduit must be regarded as the "gold standard" technique of urinary diversion, many long-term complications result and patients must wear urinary collection devices with their associated psychological and social limitations. The recent interest in continent diversions was primarily an attempt to improve the quality of life rather than improve survival or reduce renal and metabolic complications. Although continent stomas can be achieved with low pressure reservoirs fashioned from detubularised or augmented bowel, many operations may be required to perfect the continent stoma. Long-term results using continent reservoirs are awaited. It seems that a bladder substitute using reconfigurated bowel is preferable to a continent reservoir but continence remains a problem and all of the techniques lack long-term follow-up. The use of bladder substitutes in females is limited by the need to use a prosthetic sphincter to achieve continence. PMID- 2202484 TI - Ultrasonic imaging for extracorporeal shockwave lithotripsy: analysis of factors in successful treatment. AB - The emergence of real-time ultrasonic imaging for extracorporeal shockwave lithotripsy poses questions regarding the factors and techniques which facilitate stone imaging for clinicians with no previous practical experience in ultrasonography. The ability of these clinicians to assess when stone disintegration has been achieved also needs to be confirmed. A wide range of data was recorded from each of 2688 lithotripsy treatments performed over a 2-year period using the EDAP LT.01 ultrasound-imaged piezoelectric lithotriptor. An analysis of these data was performed using a comprehensive microcomputer-based statistics package. The mean time taken for stone imaging and positioning was reduced from 11.2 to 7.5 min over the 2-year period. Obese patients and those with renal pelvic stones were best imaged in a lateral position. Overall there was no difference in percentage stone disintegration or clearance between treatments in the supine or lateral positions, but a significant reduction in the clearance of small caliceal stones resulted when the lateral position was used. Factors associated with a significantly greater percentage of stone disintegration and clearance included pain experienced by the patient during fine adjustment of the processing head during treatment, acoustic focus attenuation and widening and acoustic shadow widening as detected by the urologist at the end of treatment. Among the factors not associated with significant alterations in the percentage of stone disintegration or clearance were the lithotriptor operator, the side or site of the calculus, obesity and shockwave frequency or power. This study confirmed the ability of urologists to develop expertise in ultrasonography for renal stone imaging and to interpret successfully the subtle signs of stone disintegration. PMID- 2202486 TI - Protease and plasminogen activator activity in human bladder carcinoma. AB - The ability of human bladder tissue extracts to cleave 14C-labelled globin in the absence and in the presence of plasminogen was assayed to quantify non-specific protease and plasminogen activator (PA) activity, respectively. In normal human bladder tissue the non-specific protease activity was approximately 2-fold higher than in tissue samples obtained from transitional cell carcinoma of the bladder (TCC). In contrast, PA activity was almost 4-fold higher in TCC than in normal transition cell epithelium. Acid-treated urine from 19 patients with TCC of the bladder exhibited significantly higher levels of plasminogen activator activity than similarly treated urine from controls. These results indicate that malignant transformation of the bladder epithelial tissue results in elevated levels of PA in the tissue and in urine. Further studies are needed to assess the potential of PA determination in the management of bladder cancer patients. PMID- 2202485 TI - Ultrasonography versus intravenous urography in the evaluation of patients with microscopic haematuria. AB - Urography and transabdominal ultrasonography of the urinary tract were compared in 193 patients with microhaematuria. Of 16 expansile lesions described at urography, 1 renal carcinoma was detected by both methods. Although the number of patients studied is too small for firm conclusions to be drawn, ultrasonography seems to offer advantages when compared with urography. PMID- 2202487 TI - Carcinoma of the prostate masquerading as rectal carcinoma. Report of 3 cases and review of the literature. AB - We present 3 patients with prostatic tumours who presented with symptoms of rectal stenosis. In all 3 cases digital examination of the rectum revealed a mass suggestive of rectal carcinoma, but carcinoma of the prostate was suspected because of other clinical features and this was confirmed by biopsy. Treatment by hormonal manipulation resulted in a dramatic improvement in symptoms. The diagnostic and management difficulties associated with this unusual presentation of carcinoma of the prostate are described, together with a review of the literature. PMID- 2202488 TI - Electron microscopic localization of gamma- and beta II-subspecies of protein kinase C in rat hippocampus. AB - The subcellular distributions of the gamma- and beta II-subspecies of protein kinase C (gamma- and beta II-PKC) were studied in the rat hippocampus by light and electron microscopic immunocytochemistry. Both subspecies were abundant in the hippocampus with distinct subcellular distributions. The immunoreactivity of gamma-PKC was observed throughout the Ammon's horn, while intense beta II-PKC immunoreactivity was observed predominantly in the CA1 region. gamma-PKC was distributed diffusely through the cytoplasm of pyramidal cells from the perikarya to the dendritic spines. In contrast, beta II-PKC was concentrated around the Golgi complex and present diffusely in distal dendrites, except for the dendritic spines. Neither PKC subspecies could be detected in the presynaptic terminal. The postsynaptic localization of gamma- and beta II-PKC in CA1 suggests that both PKC subspecies may correlate to long-term potentiation in the CA1 region contributing to the postsynaptic side. gamma-PKC may have a specific function not only in CA1 but also in the mossy fiber-CA3 pathway at the postsynaptic side. beta II-PKC may have another function concerning the Golgi complex in CA1. PMID- 2202489 TI - Transplantation of serotonergic neurons into the 5,7-DHT-lesioned rat olfactory bulb restores the parameters of kindling. AB - In order to restore a normal pattern of kindling, kindled rats, previously lesioned in the olfactory nuclei with 5,7-dihydroxytryptamine, were grafted with serotonin (5-HT) neurons in the right olfactory bulb and then implanted for kindling procedure. It was observed that complete 5-HT lesions accelerated the kindling profile, and that the transplants containing 5-HT neurons restored, in lesioned rats, quite normal parameters. PMID- 2202490 TI - Effects of unilateral intrahippocampal injection of MK-801 upon local cerebral glucose utilisation in conscious rats. AB - The effects of unilateral intrahippocampal injections of the non-competitive NMDA receptor antagonist, MK-801, on local cerebral glucose utilisation have been examined in conscious rats using [14C]2-deoxyglucose autoradiography. The intrahippocampal injection of MK-801 (10 nmol) induced significant marked increases in glucose use in the ipsilateral hippocampus molecular layer and dentate gyrus (by 31 and 44%, respectively). Function-related glucose use in brain regions with known neuronal connections with the site of drug administration (e.g. entorhinal cortex, septal nucleus, mamillary body) was minimally altered after intrahippocampal MK-801 administration. Blockade of hippocampal NMDA receptors does not appear to modify activity, as reflected in local glucose utilisation, in hippocampal afferent and efferent circuits in conscious rats. PMID- 2202491 TI - Preferential histochemical staining of protoplasmic and fibrous astrocytes in rat CNS with GFAP antibodies using different fixatives. AB - Serial sections of rat brain and spinal cord were fixed in either acid-alcohol or 4% paraformaldehyde, and stained for visualization of astrocytes using GFAP antibodies. With paraformaldehyde, GFAP-positive astrocytes were visualised almost exclusively in the grey matter of all above tissues. In sharp contrast, acid-alcohol treatment gave intensely stained GFAP-containing astrocytes in the white matter. Since fibrous astrocytes are mainly located in the white matter and protoplasmic astrocytes are located in the grey matter, it is concluded that acid alcohol is a good fixative for fibrous astrocytes while paraformaldehyde is a better fixative for protoplasmic astrocytes. PMID- 2202494 TI - Mineral and vitamin intoxication in horses. AB - Horses are subject to poisoning from many sources. This article considers poisonings from minerals and vitamins of nutritional significance and from minerals as environmental contaminants. PMID- 2202492 TI - Effects of endothelin on blood vessels of the brain and choroid plexus. AB - Endothelin is a recently described vasoactive peptide produced by endothelial cells. Receptors for endothelin are found throughout the brain, and are particularly dense in the choroid plexus. Effects of endothelin on cerebral blood flow and blood flow to the choroid plexus are not known. In this study, we examined effects of endothelin (100 and 1000 ng/kg i.v.) on regional blood flow (microspheres) and cerebral microvascular pressure in anesthetized rabbits. Endothelin (1000 ng/kg) produced only a 4 +/- 2 mm Hg (mean +/- S.E.M.) increase in systemic blood pressure, and had no effect on cerebral blood flow or cerebral microvascular pressure. In contrast, endothelin produced a marked decrease in blood flow to the choroid plexus and dura mater. Blood flow to choroid and dura remained significantly decreased 1 h after administration of the peptide. Endothelin also reduced blood flow to the kidney and small intestine, but the decreases tended to be less than in choroid plexus or dura mater. Thus, circulating endothelin, at doses that have no effect on cerebral blood vessels, has marked effects on blood flow to the choroid plexus. These findings suggest that circulating or locally produced endothelin may contribute to regulation of brain fluid balance through effects on choroid plexus and production of cerebrospinal fluid. PMID- 2202493 TI - Electrolytes: clinical applications. AB - Many factors can influence electrolytes in the horse. With the major electrolytes (sodium and potassium), alterations in serum or plasma values do not reflect changes in total body status. However, estimates of electrolyte alterations may be made by combining assessments of body weight changes with plasma sodium values by using the formula of Edelman et al. In planning electrolyte therapy, it has to be remembered that access to green feed or hay is important in correcting any total body potassium depletion and that diets marginal in sodium may interfere with exercise capacity by limiting sweat production. Free access to salt would seem to be the simplest method to ensure adequate sodium availability. Despite the widespread use of various commercial electrolyte supplements administered in horses' feed, most would appear to be unwarranted. Extensive electrolyte deficits are most likely in endurance horses in which substantial electrolyte losses can occur in the sweat. In such cases and when access to grass or hay is limited, supplementation with sodium and potassium chloride may be useful. Bicarbonate administration appears to have no clinical role in endurance or pleasure horses. However, its use as a buffer to limit the extent of lactic acidosis during galloping exercise has not been resolved. PMID- 2202495 TI - Ingestive behavior. AB - In summary, horses spend 60% or more of their time eating when grazing or when feed is available free choice. Grasses are their preferred food, but they supplement the grass with herbs and woody plants. Sweetened mixtures of oats and corn are the most preferred concentrate. Horses can increase or decrease the time spent eating and amount eaten to maintain caloric intake. Their intake is stimulated by drugs such as diazepam and by the presence of other horses. Horses stop eating when gastric osmolality increases; increases in plasma osmolality, protein, and glucose accompany digestion. Foals eat several times an hour and begin sampling solid food at the same time that their dam is eating. Several areas of particular importance to the equine industry have not been investigated. These areas include the effect of exercise on short- and long-term food intake and the influence of reproductive state on the feeding of mares. PMID- 2202497 TI - Environmental effects on thermoregulation and nutrition of horses. AB - Horses are reared in all types of weather. Temperatures as diverse as -40 degrees C to 40 degrees C are tolerated by horses. The nutrient requirement most influenced by cold weather is energy. In cold weather, feeding good quality hays free-choice is usually sufficient for mature horses in good body condition. Grain may have to be fed when poor quality hays are used. Hot weather (greater than 30 degrees C) necessitates heat loss to maintain body core temperature. Horses sweat to reduce body heat. Heat stress can be minimized by feeding diets that reduce the heat increment. Use of grain and fat in the diet, which have a lower heat increment than fibrous feeds such as hays, may benefit horses in hot climates. Wind or precipitation necessitate protection to minimize chilling in cold weather and discomfort in hot weather. However, it is a moot point whether horses will use shelters under these circumstances. PMID- 2202496 TI - Clinical nutrition of adult horses. AB - Horses suffering from trauma, sepsis, and severe burns need 12% to 16% of protein (dry matter basis) in their diet. Since reduced appetite may be a problem, relatively energy dense (greater than 2 Mcal DE/kg) feeds should be offered. In hepatic failure, maintenance protein requirements (8% on a dry matter basis for adult horses) should be met with feeds that are high in short branched-chain amino acids and arginine but low in aromatic amino acids and tryptophan (for example, milo, corn, soybean, or linseed meal) in addition to grass hay. Vitamins A, C, and E should also be supplemented. In cases with renal failure, protein, calcium, and phosphorus should be restricted to maintenance or lower levels. Grass hay and corn are the best feeds for horses with reduced renal function. Do not offer free-choice salt to horses with dependent edema from uncompensated chronic heart failure. Following gastrointestinal resection, legume hay and grain mixtures are the feeds of choice. Horses with diarrhea should not be deprived or oral or enteral alimentation for prolonged periods of time. Liquid formulas may be used if bulk or gastrointestinal motility are a problem. Apple cider vinegar and a high grain diet may reduce the incidence of enteroliths in horses prone to this problem. Pelleted feeds will reduce fecal volume and produce softer feces for horses that have had rectovaginal lacerations or surgery. Horses with small intestinal dysfunction or resection should be offered low residue diets initially, but long-term maintenance requires diets that promote large intestinal digestion (alfalfa hay, vegetable oil, restricted grain). Geriatric horses (greater than 20 years old need diets similar to those recommended for horses 6 to 18 months old. PMID- 2202498 TI - A conceptual approach to optimal nutrition of brood mares. AB - Cumulative nutritional demands on good brood mares are unrivalled among domestic livestock, but little attention has been given to the influence of nutrition on their reproductive performance and efficiency. We suggest that part of the decline in racing performance of progeny of mares over 10 years of age may be caused by suboptimal nutrition. This article contrasts the concepts of minimal and optimal nutrient requirements, revives Hammond's concept of nutrient partitioning to the conceptus and mammary gland, and discusses energy and nutrient requirements during gestation and lactation. Further consideration is given to the aged brood mare. PMID- 2202499 TI - Nutrition and fuel utilization in the athletic horse. AB - Substrate depletion and end product accumulation are two important factors in exercise fatigue. Fatigue during long-term exercise results from a depletion of muscle and liver glycogen and coincides with an inability to maintain blood glucose levels. During high intensity exercise, the rapid catabolism of carbohydrate and the resultant production of lactate and hydrogen ions cause a reduction in muscle pH that inhibits maximum force generation. Dietary manipulations that can influence carbohydrate status or lactate accumulation may be beneficial to performance. In human athletes, carbohydrate loading and carbohydrate supplementation can enhance endurance time during long-term exercise. These practices have not been explored extensively in the equine athlete, although glycogen loading does not enhance the performance of horses during short-term intense work. Short-term work can be detrimentally affected if glycogen levels are inadequate. The most marked effect of exercise on nutrient requirements is in the energy requirement. Horses in heavy training may require more energy than they can consume on a conventional diet. Fat has been added to horse diets to increase energy density, usually at levels between 6% and 12% of the total diet. Although protein requirements may be slightly increased in the working horse, supplementing protein as a means of adding calories is not an efficient practice. In addition, although studies with horses are not available, human studies indicate that there are no benefits to vitamin supplementation above required levels. At this point, more is unknown than is known about feeding performance horses. Most information on fuel utilization is extrapolated from studies with rats and humans. Areas that have received little attention but are critical to optimizing feeding practices are the timing of pre-event feeding and the determination of ideal body composition in equine athletes of different types. PMID- 2202500 TI - Molds, mycotoxins, and mycotoxicosis. AB - Interest in mycotoxins and mycotoxicosis in humans and animals has greatly increased in recent years. Horses have long been considered very susceptible to molds. The signs, treatment, and prevention of several conditions, such as leukoencephalomalacia, aflatoxicosis, ergotism, fescue toxicity, slobbering disease, ryegrass staggers, and moldy sweet clover disease, are discussed. PMID- 2202501 TI - Feeding and digestive problems in horses. Physiologic responses to a concentrated meal. AB - The association of feeding practices with the development of digestive disorders in horses has long been recognized, although the underlying mechanisms had been barely considered. The physiologic consequences of meal frequency may help to explain the relationship and prove to be of major significance in the induction of many conditions. Many Equidae kept for performance and leisure activities are fed high-energy, low-forage rations twice daily, with limited access to hay or grazing. Rapid ingestion of such meals stimulates a copious outpouring of upper alimentary secretions and results in transient hypovolemia (15% plasma volume loss). Subsequent activation of the renin-angiotensin-aldosterone system (RAAS) contributes to the preservation of circulatory status. Large meals may accelerate digesta passage to the cecum and, thereby, increase soluble carbohydrate availability for large intestinal fermentation. Intense periods of fermentation develop that require significant shifts of fluid into the colonic lumen. This is followed by net fluid absorption, which, in part, is dependent on postprandial increases of aldosterone. Potential consequences of these events include (1) imbalances in the RAAS response, which may promote conditions favorable to gastrointestinal disturbance, notably large intestinal impaction, and (2) changes in the gastrointestinal microflora, which may affect the intraluminal endotoxin pool and the population of enterotoxin-producing bacteria. In contrast to episodic feedings, similar changes are absent or greatly attenuated under simulated grazing conditions (for example, small, frequent meals). Thus, modification of management practices to facilitate a more continuous feeding pattern may significantly reduce the incidence of digestive problems in the stabled horse. PMID- 2202502 TI - Dietary aspects of developmental orthopedic disease in young horses. AB - The clinician may choose between two approaches to nutritional intervention. One is to evaluate the ration and make a painstaking effort to identify those specific factors operating in a particular case, then correct them. The second is to evaluate the ration, inspect for obvious aberrations, and, if finding none, proceed with no further delay to formulate an optimal diet, or a series, for the animals, and design a feeding program to suit farm management. Veterinarians should counsel clients on the possible or probable consequences of level of feeding on growth rate and clinical expression of DOD. In our view, retardation of growth rate by feeding poor quality hay is irresponsible. At present, we suggest that the new approach to retarded growth in weanlings and yearlings--a carefully formulated diet that specifically restricts starch and protein while supplying NRC minimum requirements of other essential nutrients--should be confined to selected individuals and be conducted under strict professional supervision. PMID- 2202503 TI - Feed additives and contaminants as a cause of equine disease. AB - The equine practitioner often encounters serious diagnostic and therapeutic challenges regarding the specific origin of a disease. Such challenges may occur when horses become unaccountably ill after consuming what was thought to be acceptable feed but which in fact was contaminated or contained additives intended for other species. Examples of such additives and contaminants are monensin, lasalocid, salinomycin, blister beetles, and such antimicrobics as lincomycin and clindamycin. PMID- 2202504 TI - Equilibrium analysis of binding of Candida albicans to human buccal epithelial cells. AB - The effect of growth temperature on the binding of Candida albicans to human buccal epithelial cells (BECs) was examined using an equilibrium of binding analysis. Candida albicans was cultured in M9 medium either for 12 h at 25 degrees C or for 9 h at 25 degrees C and then shifted to 37 degrees C for 3 h. The temperature shift did not result in germ tube formation; however, the adherence of C. albicans to BECs was altered. Shifting temperature increased the yeast's ability to bind to BECs. A Langmuir adsorption isotherm was used to calculate the maximum number of available binding sites (N) and the apparent association constants of binding (Ka) for all resolvable adhesin-receptor interactions. Three classes of adhesin-receptor interactions were resolved when the yeast was cultured at 25 degrees C and included a low copy number site (N = 3.0 cfu/BEC; Ka = 2.11 X 10(-6) mL/cfu), a medium copy number site (N = 23.6 cfu/BEC, Ka = 8.21 X 10(-7) mL/cfu), and a high copy number site (N = 91.7 cfu/BEC, Ka = 3.35 X 10(-8) mL/cfu). Two classes of adhesin-receptor interactions were resolved when the incubation temperature was shifted to 37 degrees C: a low copy number site (N = 4.5 cfu/BEC, Ka = 3.98 X 10(-6) mL/cfu) and a high copy number site (N = 150.5 cfu/BEC, Ka = 8.47 X 10(-8) mL/cfu). Augmented C. albicans adherence to BECs due to the elevated growth temperatures appears to result from a temperature-regulated alteration in the C. albicans adhesin that recognizes a high copy number receptor site with relatively low affinity. PMID- 2202505 TI - Aggregation of Actinomyces strains by extracellular vesicles produced by Bacteroides gingivalis. AB - The aggregation of Actinomyces viscosus and Actinomyces naeslundii with extracellular vesicles of Bacteroides gingivalis was studied. Factors influencing the aggregation phenomenon were examined. L-Arginine was found to effectively inhibit aggregation as was an antibody preparation directed against a B. gingivalis surface hemagglutinin. Aggregation occurred over a wide pH range and did not seem to be affected by high salt concentrations or the presence of carbohydrates. Treatment of the vesicle preparation with proteases, sodium dodecyl sulphate, and high temperatures diminished or eliminated aggregation, while similar treatment of the Actinomyces had no effect on aggregation. PMID- 2202506 TI - Surviving a crash landing: a software review. PMID- 2202507 TI - Clinical research. PMID- 2202508 TI - Anchoring fibrils and type VII collagen in human breast. AB - A correlated ultrastructural and immunofluorescent study of anchoring fibrils and their principal constituent, type VII collagen, has been carried out on lobular epithelium from the normal adult human breast at different times in the menstrual cycle. Throughout the cycle, characteristic, cross-banded anchoring fibrils were seen inserting into the area of lamina densa opposite the myoepithelial hemi desmosomes and in contact with anchoring-plaques. Strong immunofluorescent staining was seen in the full thickness of the zone between the basement membrane and the delimiting fibroblasts. The data establish anchoring fibrils and their type VII collagen nature as readily identifiable components of the epithelial stromal interface in breast tissues and their significance, especially in the diagnostic context, is discussed. PMID- 2202509 TI - An update on the in vitro activity of ceftizoxime and other cephalosporin/cephamycin antimicrobial agents against clinically significant anaerobic bacteria. AB - The in vitro activity of certain beta-lactam agents against aerobic and anaerobic bacteria is influenced by the method and medium used for susceptibility testing. The in vitro activity of ceftizoxime and cefoxitin against Bacteroides fragilis group strains varies when either the broth microdilution or agar dilution method is used. In general, minimal inhibitory concentration values from broth microdilution are two- to fourfold lower than those from agar dilution. Broth microdilution test results with ceftizoxime have recently been shown to correlate more closely with clinical outcome in patients than those from agar dilution testing. Broth microdilution has become the recommended method of the National Committee for Clinical Laboratory Standards for testing ceftizoxime. Using broth microdilution testing, the in vitro activity of ceftizoxime has been shown to be as good as or better than that of cefoxitin, cefotetan, and cefotaxime against anaerobes, including the B fragilis group. Ceftizoxime also had good activity against B fragilis group strains resistant to cefoxitin or cefotetan. Time-kill kinetic studies have shown that the bactericidal activity of ceftizoxime is equal to or greater than that of cefoxitin or cefotetan against both cefoxitin susceptible or cefoxitin-resistant strains of the B fragilis group. PMID- 2202510 TI - Gangrenous and perforated appendicitis with peritonitis: treatment and bacteriology. AB - A comparison of single-agent antimicrobial therapy in the treatment of patients with perforated or gangrenous appendicitis and peritonitis was performed in a double-blind, randomized, prospective trial. Pathologic documentation of advanced appendicitis and positive intraoperative specimen cultures were required for inclusion in the study. Ceftizoxime (2 gm every 12 hours) and cefoxitin (2 gm every six hours) were compared. There were no significant differences between the treatment groups. Ninety-seven percent of patients treated with ceftizoxime and 89% of those treated with cefoxitin were cured or improved; there was no mortality in either group. By the use of optimal sampling, transport, and culture techniques, the number and diversity of bacteria recovered from these patients with advanced appendicitis were found to be much larger than previously suspected. Peritoneal fluid, abscess contents (if present), and appendiceal tissue (obtained so as to exclude the lumen) were cultured from all patients. An average number of 3.1 aerobic or facultative bacteria species and 8.5 anaerobic species were isolated from each specimen. Twenty-eight different genera and more than 55 species were encountered, including a previously undescribed fastidious gram-negative anaerobic bacillus. Bacteroides fragilis group and Escherichia coli were isolated from almost all specimens, and within the B fragilis group, eight species were represented. The recovery of such an unexpectedly large and diverse flora may be the reason for the therapeutic failures in these patients. We conclude that single-agent antimicrobial therapy in patients with advanced appendicitis and peritonitis is both safe and effective, and, with ceftizoxime, can be accomplished by a twice-daily dosing regimen. PMID- 2202511 TI - Comparison of single-dose ceftizoxime with multidose cefoxitin chemoprophylaxis for patients undergoing hysterectomy. AB - A single dose of ceftizoxime was comparable to three perioperative doses of cefoxitin as adjunctive antibiotic chemoprophylaxis against infectious morbidity in women undergoing elective abdominal (60% of patients) or vaginal (40% of patients) hysterectomy. In a double-blind, randomized, prospective, controlled trial, patients were randomized to receive either a single 1-gm dose of ceftizoxime, a newer, broadly active cephalosporin, or three 2-gm doses of cefoxitin intravenously. Twenty-nine women treated with ceftizoxime and 33 women treated with cefoxitin were evaluated. Patient groups were similar for age, other demographic factors, indications for surgery, surgical procedures performed, and selected microbiologic findings. Postoperative infectious morbidity requiring antibiotic treatment was similar among women who received ceftizoxime (27.6%) and those receiving cefoxitin (33%) (P = 0.6). Women receiving ceftizoxime also required a similar number of days of hospitalization (ceftizoxime, 4.7 +/- 1.7 days; cefoxitin, 5.6 +/- 4.5 days; P = 0.3). Both study drugs appeared to be safe and well tolerated. Single-dose ceftizoxime appears to be as efficacious as and more cost-effective than multidose cefoxitin when used as adjunctive chemoprophylaxis in patients at risk for postoperative infection after hysterectomy. PMID- 2202512 TI - A comparison of the efficacy and safety of ceftizoxime with doxycycline versus conventional CDC therapies in the treatment of upper genital tract infection with or without a mass. AB - It is well known that sexually transmitted infections of the upper genital tract are widespread. A variety of regimens are used to treat these conditions, many of which have not been subjected to randomized, prospective clinical trials (including the 1985 Centers for Disease Control [CDC] Guidelines for the treatment of upper genital tract infections [UGTI]). This investigation was undertaken to compare the 1985 CDC treatment guidelines with different doses of ceftizoxime, a third-generation cephalosporin with an intermediate half-life, plus doxycycline in patients with UGTI. The patients were divided into subgroups, depending on the presence or absence of a pelvic mass. Sixty-seven women participated in the study. They were older than 14 years of age and required hospitalization for the treatment of UGTI. These women had lower abdominal pain and tenderness, cervical motion or adnexal tenderness, and one of the following: temperature greater than 100.4 degrees F orally, leukocytosis greater than 10,500/mm3, or presence of a suspected inflammatory pelvic mass on pelvic examination or by ultrasound. Informed consent was obtained from all patients in a manner approved by the Institutional Review Board. Pelvic examinations and ultrasound evaluations of the pelvic soft tissues were performed on all patients at the time of admission. Those who were found not to have a pelvic mass or who had a pelvic mass less than 4 cm in transverse diameter were randomly allocated to receive either ceftizoxime 2 gm intravenously every 12 hours with doxycycline 100 mg intravenously twice daily (Rx 1, n = 13) or cefoxitin 2 gm intravenously every six hours with doxycycline 100 mg intravenously twice daily (Rx 2, n = 14). Those patients found to have a pelvic mass (greater than 4 cm in transverse diameter) were randomly allocated to receive either ceftizoxime 2 gm intravenously every eight hours with doxycycline 100 mg intravenously twice daily (Rx 3, n = 19) or clindamycin 900 mg intravenously every eight hours with a 2 mg/kg loading dose of gentamicin followed by 1.5 mg/kg intravenously every eight hours, with adjustments as necessary (Rx 4, n = 21). All UGTI patients without a mass treated with either Rx 1 or Rx 2 responded adequately. However, UGTI patients with a mass treated with Rx 4 were more likely than those treated with Rx 3 to require a change in antibiotics or need extirpative surgery in order to obtain a satisfactory clinical response (Fisher's exact test = 0.046, two sided).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2202514 TI - Epidermal cell kinetics of the pig: a review. AB - Age-related changes in cell kinetic parameters for the epidermis of pigs have been shown to be small, indicating that young pigs may be used for experimental studies. It was not possible to draw any firm conclusions about any strain related differences in the cell kinetics of the epidermis of the pig. Lower LI values have been quoted for the miniature pig and the Yorkshire pig than for the Large White pig. However, these differences may be related to variations in experimental technique. The cell kinetic data for the Yorkshire pig are not consistent. Very high values for the mitotic index suggested a high rate of cell turnover, whilst data from single pulse labelling and grain count halving studies indicate a relatively low rate of cell turnover. The results from continuous labelling studies on the epidermis of the Yorkshire pig suggest that the basal cell turnover time (TT) is a factor of two or more shorter (136 h) than the estimates obtained using other methods. In the Large White pig estimates of TT were similar using a variety of techniques and were comparable with the TT estimate for the Yorkshire pig obtained using the continuous labelling method. There is some degree of inconsistency in the literature with regard to possible diurnal variations in the cell kinetic parameters for the epidermis. In the study of Archambeau & Bennet (1984) distinct diurnal variations were found in the LI, although the reliability of this finding is questionable due to the small number of animals used. Later studies by Morris et al. (1987) have suggested that diurnal variations are negligible in the epidermis of the pig. The majority of labelled cells (80%) in pig epidermis are located in the basal layer, although a significant proportion (20%) occurs suprabasally, in the cell layer immediately above the basal layer. Therefore, the epidermis can be regarded as having a bilayered proliferative cell compartment. The results from studies on irradiated pig skin (Morris & Hopewell, 1986, 1988, 1989) are not consistent with the presence of a homogeneous proliferative compartment in the epidermis, and are best explained by the occurrence of an heterogeneous proliferative compartment consisting of a stem cell subpopulation and a much larger population of transit proliferative cells. PMID- 2202513 TI - Interchangeability of ceftizoxime and cefoxitin: a clinical perspective. AB - Ceftizoxime and cefoxitin, two parenteral broad-spectrum cephalosporin antibiotics, were compared in a prospective, randomized, double-blind study to determine if they are clinically equivalent in the treatment of infections of the urinary or respiratory tracts, the intra-abdominal cavity, or skin and skin structure. Since the pharmacokinetic properties of ceftizoxime permit less frequent dosing than cefoxitin and, in consequence, lower daily doses, a second objective was to compare the cost of intravenous use of these antibiotics in hospital practice. Patients were assigned at random to treatment with either 4 to 8 gm/day of cefoxitin or 2 to 4 gm/day of ceftizoxime. Within each treatment group, they were stratified according to the site of the infection. Cure rates were similar with ceftizoxime (96% of 134 patients) and cefoxitin (92% of 132 patients). There were no statistically significant differences with respect to site or severity of infection. An analysis of the cost of the drugs and the labor to administer them showed ceftizoxime to be less expensive ($263 to $389/day) than cefoxitin ($394 to $638/day). PMID- 2202515 TI - A mathematical model of erythropoiesis in mice and rats. Part 4: Differences between bone marrow and spleen. AB - In a preceding analysis we hypothesized that the most important parameter controlled by erythropoietic regulation in vivo is the degree of amplification (number of cell divisions) in the CFU-E and erythroblast cell stages. It was concluded that erythropoietic amplification in vivo is controlled according to a sigmoidal dose-response relationship with respect to the control parameter which is the haematocrit (or haemoglobin concentration). Here, this hypothesis is extended to include the differences in murine bone marrow and splenic erythropoiesis that are described and quantified by different dose-response relationships. Comparing several sets of experimental data with mathematical model simulations, this approach leads to the following conclusions: (i) in the unperturbed normal steady state at least one extra erythropoietic cell division takes place in the spleen compared with the bone marrow; (ii) a strong erythropoietic stimulus, such as severe bleeding or hypoxia, can induce five to six additional cell divisions in the spleen but only two to three additional divisions in the bone marrow; this results in a considerable increase in the spleen's contribution to erythropoiesis from about 10% in normal animals to over 40% during strong stimulation; (iii) under erythropoietic suppression, such as red cell transfusion, a similar number of cell divisions is skipped in both organs and the splenic contribution to erythropoiesis remains unchanged. In conclusion, the concept that bone marrow and spleen microenvironments differ in the dose-response relationship for erythropoietic regulation provides an explanation for the changing contribution of splenic murine erythropoiesis following a variety of experimental treatments. PMID- 2202516 TI - Double labelling of cells with tritiated thymidine and bromodeoxyuridine reveals a circadian rhythm-dependent variation in duration of DNA synthesis and S phase flux rates in rodent oral epithelium. AB - We describe a double labelling method for estimating the duration of DNA synthesis (Ts) and the flux of cells into and from the S phase of the cell cycle, based on labelling with tritiated thymidine [( 3H]TdR) followed by bromodeoxyuridine (BrdU) and combining immunohistological detection of BrdU with conventional autoradiography. In practice, the change in size of a window of double labelled cells occurs as the time interval between the two labels increases. In mouse tongue epithelium there is a marked circadian variation in the number of cells in DNA synthesis. From 0900 to 1500 h this labelling index (LI) falls, but from 2100 to 0300 h it increases. Our results show that the circadian decrease in LI is associated with a short Ts (5.8 +/- 0.3 h), a high S phase efflux and an initially low influx of cells from G1 into S. Conversely, the rising circadian LI is associated with a longer Ts (9.4 +/- 0.1 h), an initially low efflux and a moderate to high influx. Two time-points exist on the circadian LI curve when influx and efflux rates change abruptly. At 0100 h the efflux rate rises from low (5 cells %/h) to high (15-16 cells %/h) and simultaneously the influx rate changes from high to low. Similarly at 1300-1400 h, efflux rate falls from high (19-20 cells %/h) to low (4-8 cells %/h) values and influx rates change from low to high. This double labelling method has revealed that the duration of DNA synthesis varies across the circadian cycle, as do influx and efflux values which generally fall within a discrete range of high or low values. The timing of the changes in flux suggests the presence of two 'control' points on the circadian LI cycle that were previously unrecognized. PMID- 2202517 TI - [A primary study on molecular epidemiology of diarrhea caused by enterotoxigenic Escherichia coli by DNA colony hybridization using three enterotoxigenic gene probes]. AB - 921 isolates of acute-diarrhea-inducing E. Coli strains from several provinces and cities, including Guangzhou, Wuhan, Sichuan, Shenyang and Hunan, have been collected during 1984-1989 and were identified in 1989 for detecting genes coding for these enterotoxins-LT, ST-P, ST-H by DNA colony hybridization using three enterotoxigenic gene probes. Of all the isolates homologous to these genes encoding LT, ST-P, ST-H and both LT and ST were 198 (21.5%), 131 (14.2%), 54 (5.9%) and 18 (2.1%), respectively. It was showed that in our country pathogenic agents of acute infectious diarrheal disease with ETEC strains first might be ETEC-LT strains, secondary ETEC-ST-H strains. Whereas, in rural districts ETEC-ST P possess higher proportion of ETEC strains. These results provided some essential data and advanced methods for researching further molecular epidemiology of the ETEC diarrheal disease. PMID- 2202518 TI - [AIDS--a new worldwide epidemic disease]. PMID- 2202519 TI - The use of microbial membranes to achieve anaerobiosis. AB - The cytoplasmic membranes of many aerobic and facultative bacteria contain enzymes that catalyze the reduction of dissolved oxygen to water. Preparations of small particles derived from such membranes can be filter sterilized without loss of the oxygen-reducing enzymes. These particle preparations can be used to produce anaerobic conditions in a variety of biological environments. They have been shown to stimulate the growth of many anaerobic bacteria and can also be used to stabilize oxygen-sensitive chemical reagents. The particle preparations are stable for long periods of time. They are functional over a pH range and temperature range frequently encountered in biological systems. Various techniques for using the particles are presented. The advantages and limitations of this new approach to achieving oxygen-free conditions are discussed. PMID- 2202520 TI - Recent advances in the generation of chiral intermediates using enzymes. AB - Different types of enzyme-catalyzed processes are reviewed, with particular regard to those procedures leading to the generation of chiral compounds of high optical purity. The main body of the review deals with hydrolyses and esterification as well as the reduction and oxidation of organic substrates. Other biotransformations of current and/or future importance in the synthesis of homochiral fine chemicals (such as the formation of carbon-carbon bonds using aldolases) are also discussed in some detail. Attention is drawn to current trends in the area and, to this end, a majority of the references are taken from journals published during the period April 1987 to September 1988. PMID- 2202521 TI - Development of new cell lines for animal cell biotechnology. AB - Mammalian cell culture has been an important technique in laboratory-scale experimentation for many decades. Developments in large-scale culture have been due to the need to grow large numbers of cells to support the growth of viruses for vaccine production, and more recently, for growing hybridoma cells as a source of monoclonal antibody. Increasingly, however, pharmaceutical products such as hormones, enzymes, growth factors, and clotting factors are being produced from cell lines which have been manipulated by recombinant DNA techniques. It is clear, therefore, that the high cost of growing mammalian cells on a large scale does not necessarily prohibit their use for biotechnology, and indeed there is considerable evidence to suggest that animal cell biotechnology will continue to be a major growth area in the future. PMID- 2202522 TI - Isolation and genetic study of triethyltin-resistant mutants of Saccharomyces cerevisiae. AB - Three mutants of Saccharomyces cerevisiae resistant to triethyltin (an inhibitor of mitochondrial ATPase) on non-fermentative media, and non-resistant to this drug on fermentative media, were isolated and named TTR1, TTR2 and TTR3. Apart from triethyltin resistance, these mutants show the following common characteristics: (1) Increased intracellular cytochrome c concentration. (2) Increased respiration rate. (3) Decreased growth yield. (4) Increased growth sensitivity to several drugs inhibiting oxidative phosphorylation: namely, CCCP (permeabilizing inner mitochondrial membrane to protons), valinomycin (permeabilizing inner mitochondrial membrane to potassium) and oligomycin (inhibitor of mitochondrial ATPase). (5) Increased sensitivity to carbon source starvation. For each mutant, these characteristics appeared to be due to a single pleiotropic nuclear mutation. Mutation TTR1 causes additional phenotypic characteristics which do not appear in mutants TTR2 and TTR3: (1) Pinkish coloration of colonies which is more pronounced after a long growth period. (2) Inability of the cells to store glycogen. (3) Growth defect of the cells on a galactose-containing medium. (4) Inability of a diploid homozygote mutant strain to sporulate. All these phenotypic characteristics have already been described in yeast mutants deregulated in cAMP-dependent protein phosphorylation. Crossing of a strain bearing the TTR1 mutation with a strain mutated in the adenylate cyclase structural gene suggested that the TTR1 phenotype is due to a modification in regulation of cAPK by cAMP, making cell multiplication possible without intracellular cAMP. PMID- 2202523 TI - Evolutionary conservation of transcriptional machinery between yeast and plants as shown by the efficient expression from the CaMV 35S promoter and 35S terminator. AB - Complementation of fission yeast mutants by plant genomic libraries could be a promising method for the isolation of novel plant genes. One important prerequisite is the functioning of plant promoters and terminators in Schizosaccharomyces pombe and Saccharomyces cerevisiae. Therefore, we studied the expression of the bacterial beta-glucuronidase (GUS) reporter gene under the control of the Cauliflower Mosaic Virus (CaMV) 35S promoter and 35S terminator. We show here that S. pombe initiates transcription at exactly the same start site as was reported for tobacco. The 35S CaMV terminator is appropriately recognized leading to a polyadenylated mRNA of the same size as obtained in plant cells transformed with the same construct. Furthermore, the GUS-mRNA is translated into fully functional GUS protein, as determined by an enzymatic assay. Interestingly, expression of the 35S promoter in the budding yeast S. cerevisiae was found to be only moderate and about hundredfold lower than in S. pombe. To investigate whether different transcript stabilities are responsible for this enormous expression difference in the two yeasts, the 35S promoter was substituted by the ADH (alcohol dehydrogenase) promoter from fission yeast. In contrast to the differential expression pattern of the 35S promoter, the ADH promoter resulted in equally high expression rates in both fission and budding yeast, comparable to the 35S promoter in S. pombe. Since the copy number of the 35S-GUS constructs differs only by a factor of two in the two yeasts, it appears that differential recognition of the 35S promoter is responsible for the different transcription rates. PMID- 2202524 TI - In vivo import of Candida tropicalis hydratase-dehydrogenase-epimerase into peroxisomes of Candida albicans. AB - We present a system for studying peroxisomal protein targeting in Candida. We have expressed the Candida tropicalis gene encoding hydratase-dehydrogenase epimerase (HDE) in Candida albicans. Immunoblot analyses of C. albicans transformants demonstrate the presence of oleic-acid inducible HDE (100 kDa) in peroxisomes of transformed cells, but not of control cells. Peroxisomes isolated from transformed cells show increased beta-hydroxyacyl-CoA dehydrogenase specific activity, indicating that HDE is imported into peroxisomes of C. albicans where it is enzymatically active. C. albicans provides a useful model for the study of protein targeting to peroxisomes in vivo. PMID- 2202527 TI - Chromosome location of a family of genes encoding different acidic ribosomal proteins in Saccharomyces cerevisiae. AB - DNA probes from the genes encoding the acidic ribosomal proteins L44, L44' and L45, as well as from reporter genes for chromosomes IV, VII, XII and XV, have been hybridised to Southern blots of Saccharomyces cerevisiae DNA resolved by pulsed field gel electrophoresis. The protein L44' and protein L45 genes have been found to hybridise to chromosome IV, identified by the CAT1 gene probe, while the protein L44 probe hybridises with a band containing chromosomes VII and XV, identified by the ATPase 1 and HIS3 genes respectively. PMID- 2202525 TI - Efficient translation of the UAG termination codon in Candida species. AB - Clinical isolates of the dimorphic fungus Candida albicans encode a tRNA that, in a cell-free translation system prepared from the yeast Saccharomyces cerevisiae, efficiently translates the amber (UAG) termination codon. Unusually, the efficiency of this UAG read-through in the heterologous cell-free system is not further enhanced by polyamines. The suppressor tRNA is also able to efficiently translate the UAG codon in the rabbit reticulocyte cell-free system and with efficiencies approaching 100% in a homologous (C. albicans) cell-free system. That the suppressor tRNA is nuclear-encoded is demonstrated by the lack of activity in purified C. albicans mitochondrial tRNAs. Finally, UAG suppressor tRNA activity is also demonstrated in three other pathogenic Candida species, C. parapsilosis, C. guillermondii and C. tropicalis. These results suggest that some, but not all, Candida species have evolved an unusual nuclear genetic code in which UAG is used as a sense codon. PMID- 2202526 TI - p-fluoro-phenylalanine resistance in Aspergillus nidulans diploid cells: evidence that dominant, lethal mutations are involved. AB - An unexpectedly large number of p-fluoro-phenylalanine (FPA)-resistant mutants have been recovered after UV-irradiation of wild type diploid conidia of Aspergillus nidulans. At least five different classes of mutants, possibly corresponding to five different loci, have been identified. Two of them may be the dominant loci which have already been described but the others (a minimum of three loci) are completely different. Mutations in these loci confer high level FPA resistance in the heterozygous diploids, being lethal in the haploids; one mutation has been preliminarily mapped to chromosome I and another to chromosome III. PMID- 2202528 TI - The absence of introns in yeast mitochondria does not abolish mitochondrial recombination. AB - The respiratory competency of a yeast strain devoid of mitochondrial introns is quite normal. However, it may be asked whether intron-encoded proteins participate in metabolisms other than those of mitochondrial introns. Using strains without mitochondrial introns we have answered two questions. The first was: does the absence of intron-encoded proteins abolish mitochondrial recombination? The second was: do mitochondrial introns and intron-encoded proteins play a part in mitochondrial DNA rearrangements induced by ethidium bromide (rho- production)? We have shown that the introns and intron-encoded proteins are not essential components of either phenomenon. PMID- 2202529 TI - [Immunogold and immunofluorescence localization of epidermal growth factor receptors on MCF-7 human breast cancer cells]. AB - Immunogold and immunofluorescence staining techniques were used for localization of epidermal growth factor (EGF) receptors on MCF-7 cell membranes. Fluorescence microscopy showed that MCF-7 cells reacted with the monoclonal antibody against EGF receptors and gave positive reaction on the membrane surface. Under electron microscope, the electron-dense gold particles were distributing on the membrane surface including the microvilli. A continued course of internalization of EGF receptors labeled with colloidal gold was observed by electron microscopy. It is considered that one of the mechanisms involving breast cancer MCF-7 cell growth and the stimulating effect on the growth of MCF-7 cells by estradiol is autocrine secretion. PMID- 2202530 TI - [Ferritin and its relation to neoplasms]. PMID- 2202531 TI - In vivo generation and elimination of angiotensin in the rat. AB - 1. Combined high performance liquid chromatography (HPLC) and radio-immunoassays were used to study the in vivo kinetics of the renin-angiotensin system in the rat. The HPLC-verified plasma concentrations of angiotensin I (AI) were 1.0 nmol/L (0.52-1.6) in anaesthetized normal and 4.2 nmol/L (2.5-7.0) in salt depleted rats. The plasma concentrations of angiotensin II (AII) were 0.07 nmol/L (0.04-0.13) in anaesthetized normal and 1.0 (0.60-1.6) nmol/L in salt-depleted rats. 2. The fate of injected AI and AII passing through the vascular bed of the lungs was determined. Two-thirds of the injected AI was converted to AII and one third was unchanged after a single passage through the lungs. Only trace amounts of angiotensin III (AIII), the only other metabolite, were demonstrated. 3. This verifies that the majority of AI is metabolized through AII. Injected AII disappeared from the circulation with formation of only trace amounts of AIII, the half-life being about 10 s. This corresponds to a calculated in vivo generation rate of AII of about 12 nmol/L per h in normal rats. It is in agreement with the AI generation rate (plasma renin activity) measured as 9.5 nmol/L per h in vitro. PMID- 2202532 TI - Immunology of atherosclerosis: cellular composition and major histocompatibility complex class II antigen expression in aortic intima, fatty streaks, and atherosclerotic plaques in young and aged human specimens. AB - There is evidence that fatty streaks in arteries can transform into atherosclerotic plaques. Mononuclear cells, including both monocytes and lymphocytes, are among the first cells participating in the development of atherosclerosis of experimental animals. To investigate the roles of different cell types in human atherosclerosis, we enumerated and compared the cellular compositions of normal intima, the transition zone (the area between the normal intima and the core of fatty streaks), fatty streaks, and plaques in young (age 16-30 years) and aged (over 60 years) human specimens using double-staining immunofluorescence with a series of monoclonal and polyclonal antibodies. T lymphocytes, both T helper/inducer (70% of T cells) and T suppressor/cytotoxic (30%) phenotypes, were found in every stage of atherosclerosis, constituting 30 to 40% of total cells in fatty streaks and transition zones of young subjects, and occasionally even in normal intima. Seventy percent of these T cells were HLA DR positive, which indicated that most of them were activated. Macrophages were most frequent in fatty streaks and around the necrotic core of plaques. Smooth muscle cells, increasing from 5 to 30% with lesion progression, were HLA-DR positive where activated T helper cells occurred in the vicinity. The intracellular presence of the invariant gamma chain confirmed that HLA-DR was actually synthesized by these smooth muscle cells. Endothelial cells were HLA-DR positive above those regions of the lesions where HLA-DR-positive cells had accumulated, but not in normal intima, again suggesting induction of HLA-DR expression by T-cell-derived gamma-interferon. Furthermore, most HLA-DR-positive cells were also identified as HLA-DP and HLA-DQ positive. This aberrant major histocompatibility complex class II antigen expression in smooth muscle and endothelial cells may participate in the perpetuation of the atherogenetic autoimmune reaction. PMID- 2202534 TI - Vascular compression of the superior infundibulum causing calyceal obstruction. Scintigraphic findings. AB - Radionuclide imaging in obstructive uropathy has concentrated on disorders of the pelviureteric junction and lower urinary tract. There is a paucity of information, however, available on the scintigraphic manifestations of disorders of the calyces and infundibulum. These conditions may be responsible for similar symptoms, and thus recognition of abnormal retention of activity within one or more calyces offers important diagnostic information. One of these disorders is vascular obstruction of the superior infundibulum, and this report describes the radionuclide appearance of this surgically curable condition. PMID- 2202535 TI - Kerley Pergamon lecture: The diaphragm. Radiologic correlations with anatomy and pathology. PMID- 2202536 TI - Colour Doppler ultrasound in deep venous thrombosis: a comparison with venography. AB - Colour Doppler ultrasound is a new technical development allowing simultaneous grey scale imaging and a dynamic colour flow vascular image. To date, many real time ultrasonic studies have been assessed in the diagnosis of lower limb venous thrombosis and have been shown to be accurate in the femoral and popliteal segments. A double blind prospective study comparing colour Doppler with contrast venography in the diagnosis of lower limb thrombosis was performed in a group of 40 patients. Of the study group, 26 venograms were negative and 27 ultrasound examinations were negative. Of the 14 positive venograms there was one false negative colour doppler scan which missed a calf and lower popliteal thrombosis. Two cases of isolated calf vein thrombosis were successfully detected by colour Doppler. Overall, the sensitivity and specificity for detection of lower limb venous thrombosis, including calf vein assessment, were 93% and 100% respectively. Colour Doppler is easy to perform; the average scanning time being 15 minutes for complete assessment of a unilateral lower limb venous system. Spontaneous flow is evident in the femoropopliteal segment, whilst proximal calf vein flow can only be appreciated with the aid of distal compression. Eccentric thrombus and partially recanalized thrombus can be shown. Although the number of isolated calf vein thromboses was small, early experience suggests colour Doppler may be useful in the assessment of proximal calf vein patency. PMID- 2202533 TI - Specificity of the suppression of metastatic phenotype by tyrosine and phenylalanine restriction. AB - Amino acid restriction modulates tumor growth, although effects on metastasis are poorly documented. We demonstrate that low levels of tyrosine (Tyr) and phenylalanine (Phe) suppress metastasis of B16-BL6 melanoma and that these effects are specific to these two amino acids. Weight loss and sustained low body weight in mice fed low Tyr and Phe diet do not contribute to the antimetastatic effects. Furthermore, methionine (Met) restriction, which decreased survival of mice inoculated i.p. with B16 melanoma, only slightly inhibited spontaneous metastasis compared to the dramatic inhibition during Tyr and Phe restriction. Tyr and Phe restriction inhibited spontaneous metastasis by impairing the ability of tumor cells to establish metastatic foci and not via differential tumor cell removal from the blood. Spontaneous metastasis is blocked by Tyr and Phe intervention even in mice with established lymph node tumors. Tumors isolated from mice fed low Tyr and Phe diet reinoculated into mice fed normal diet exhibited lower experimental metastatic potential, reflected by decreased formation of lung tumor colonies and increased survival of inoculated mice. This decrease in metastatic potential is not associated with tumor chemosensitivity. These findings indicate that Tyr and Phe restriction could become an important adjuvant to effective melanoma treatment. PMID- 2202537 TI - Comparison of temperature profiles (DeVeTherm) and conventional venography in suspected lower limb thrombosis. AB - In 124 patients admitted with suspected acute deep venous thrombosis, the screening value of a new thermographic scanner, DeVeTherm, was evaluated using conventional venography as a reference. The sensitivity of the scanner was calculated at 92% and the specificity at 25%. The predictive value of positive temperature profiles was 0.48, and that of negative temperature profiles, 0.82. On the basis of these results neither the accuracy nor the potential savings justify using temperature profiles alone as a screening test for this condition. PMID- 2202538 TI - The value of immediate ultrasound in acute abdominal conditions: a critical appraisal. AB - A randomized prospective controlled trial was carried out comparing the value of immediate ultrasound examination with conventional management (selective ultrasound examination) in patients with acute abdominal symptoms. Immediate ultrasound led to earlier establishment of a final diagnosis but did not shorten the duration of in-patient care. Selective ultrasound improved diagnostic yield compared to immediate ultrasound and is believed to be the better option. It implies that a prompt but selective ultrasound service should be available for in patients in the acute specialties. PMID- 2202539 TI - Paediatric Wegener's granulomatosis: two case histories and a review of the literature. AB - Wegener's granulomatosis is a rare disease in children, with only 37 previous cases described in the literature. We report two new cases, one in an 11-year-old child who presented with cavitating nodules in the right upper lung field as well as a maxillary sinusitis and nasal perforation, and the other in a 16-year-old female who initially presented with a purulent maxillary sinusitis and only later developed an orbital pseudotumour. PMID- 2202540 TI - Salmonella aortitis and aneurysm formation: the role of CT in management. AB - A case of salmonella aortitis and aneurysm formation with subsequent necrosis of the arterial wall is described. Computed tomography is beneficial in diagnosis and management and should be carried out early in the course of illness. PMID- 2202541 TI - Possibilities for the immunotherapy of rheumatoid arthritis. PMID- 2202542 TI - Determination of anti-ds-DNA antibodies by three different methods: comparison of sensitivity, specificity and correlation with lupus activity index (LAI). AB - Ninety-seven sera, 58 from patients with SLE and 39 from patients with other autoimmune rheumatic diseases were tested for anti-ds-DNA antibody activity by ELISA, Farr, and Crithidia Lucilliae assays. Fifty-six per cent of the sera were positive by at least one method. Eighty per cent of the SLE population was positive by ELISA, 39% by Farr Assay and 33% by the Crithidia assay. Crithidia assay exhibited the greater specificity (100%) followed by the Farr Assay (97%) and the ELISA (80%). Sera positive by all methods showed a significantly higher mean value of the ELISA rates, than sera positive only by ELISA (p less than 0.001). When the SLE sera were analyzed according to disease activity, it was shown that ELISA and Farr Assay correlated well with the lupus activity index (LAI) (r less than 0.001). The SLE sera with the higher anti-ds-DNA concentration (sera positive by all 3 methods) did not correlate with LAI when tested by the Farr Assay (0.05 less than p less than 01) in contrast to the ELISA values, which correlated very well (p less than 0.01). Our results indicated that the ELISA is the most sensitive method with reasonable specificity as well. In addition, the ELISA anti-DNA values correlate with the clinical activity of lupus, independently of the anti-ds-DNA levels in the sera. The latter should be attributed to the fact that this method detects all the heterogenous population of anti-ds-DNA. PMID- 2202543 TI - Increased plasma fibronectin in patients with systemic lupus erythematosus. AB - To add to our knowledge of collagen diseases, plasma fibronectin (FN) in patients with systemic lupus erythematosus (SLE) has been measured, and it was determined that the plasma FN value in those with SLE was 454 +/- 36 micrograms/ml, is significantly higher than the FN value in normal subjects (234 +/- 21 micrograms/ml) than that of patients with FN value of patients with active SLE was significantly higher (591 +/- 46 micrograms/ml) that of the patients with non active SLE (287 +/- 31 micrograms/ml). The plasma FN value of SLE patients was also seen to be associated with the peripheral blood platelet count and with the dose level of the corticosteroid hormone administered to patients. In active SLE patients, it was similarly found that the plasma FN value had a significant correlation with the peripheral blood lymphocyte count and with the dose level of the corticosteroid hormone given to patients. Since the plasma FN value is known to be high in untreated SLE patients, it was felt that the increase of the FN value in SLE patients is not due to the effect of the corticosteroid but to the disease itself. PMID- 2202544 TI - A controlled comparison of piroxicam and diclofenac in patients with osteoarthritis. AB - Eighty patients with osteoarthritis were randomly assigned to either piroxicam (20 mg daily) or diclofenac (75-150 mg daily) in a 12-week double-blind, parallel groups study. In the 70 patients who completed the study, both medications were effective; statistically significant improvement was observed on all assessments of efficacy. However, no statistically significant differences between the two drugs were seen on any of the efficacy parameters measured. There was a trend towards better tolerance in the piroxicam treated patients, although this was not statistically significant; 3 of the 40 piroxicam treated patients versus 6 of the 40 patients on diclofenac were discontinued from the trial due to intolerable adverse events. PMID- 2202545 TI - Energy balance and pulsatile LH secretion in early postpartum dairy cattle. AB - The relationships between energy balance (EB), pulsatile LH secretion and circulating levels of insulin and various energy metabolites were assessed in ten lactating Holstein cows. Cows were blood sampled every 12 min via indwelling jugular catheters for 8 hr twice weekly beginning in the first week postpartum (PP) through first ovulation (1stOV). Days to negative EB nadir and days to 1stOV were highly correlated (P less than .02). LH pulse frequency (P less than .01), LH baseline (P less than .05) and mean LH (P less than .1) increased, while LH pulse amplitude tended to decrease when comparing the frequent sampling series immediately before and after the negative EB nadir. Plasma levels of non esterified fatty acids (NEFA, r = -.40, P less than .01), insulin (r = .38, P less than .01), glucose (r = .31, P less than .01) and beta-hydroxybutyrate (r = .19, P less than .06) were correlated with EB. For within animal comparisons, NEFA was significantly correlated (r = -.44 to -.89, P less than .05) with EB in 8 of 10 cows, but no other correlations were significant. Additionally, none of the metabolites nor insulin were significant in multiple regression models for 1stOV. Therefore, it appears that pulsatile LH secretion is suppressed until the negative EB nadir is reached, at which time LH pulse frequency increases stimulating 1stOV. Since NEFA and EB are directly related, NEFA may serve as a peripheral signal of EB to the central nervous system. PMID- 2202546 TI - Growth hormone, insulin, prolactin and glucose levels in ewe and ram lambs during normal and compensatory growth. AB - Two trials were conducted to determine the effect of compensatory growth on plasma glucose and serum growth hormone (GH), prolactin (PRL) and insulin concentrations in lambs. The trials consisted of a normal growth (NG) period (4 to 7 mo of age), a restricted feed/weight loss period and a compensatory growth (CG) period. The lambs in Trial 1 were 13 mo of age and in Trial 2, 11 mo of age at the start of the respective CG periods. Compensatory growth rate was 61 to 67% greater than NG rate in Trial 1 and 2, respectively. Twenty-four hour blood collections were performed during NG and CG in each trial. Normal growth blood collection for Trial 1 was performed in April (ram, n = 7; ewe, n = 6) and the CG blood collection in November (ram, n = 6; ewe, n = 6) while for Trial 2 blood collection dates were November (ram, n = 6; ewe n = 6) and March (ram, n = 4; ewe, n = 5). Trial 1 ram lambs had lower plasma glucose concentrations during CG than during NG while plasma glucose concentration was not altered in ewe lambs. Type of growth had no effect on plasma glucose in Trial 2. There was a type of growth by sex interaction for insulin in both Trial 1 and Trial 2. Insulin concentration decreased during CG in ram lambs but remained unchanged (Trial 1) or increased in ewe lambs (Trial 2) during CG. The effect of CG on PRL concentration in Trial 1 was confounded by photoperiod and the only effect in Trial 2 was a small decrease in the amplitude of PRL peaks during CG. The overall mean GH concentration (GHmn) was increased (P less than 0.01) two fold during CG in Trial 1. This effect was also seen in Trial 2 but the increase was sex dependent (P less than 0.005) with the effect of CG on GHmn in ram lambs being six times that seen in ewe lambs. The GH profile characteristics responsible for the increase in GHmn during CG differed between sexes and trials. PMID- 2202547 TI - A dose finding study of the combination of atenolol and nifedipine in hypertension. AB - A randomized, double-blind, crossover study was carried out to compare the antihypertensive efficacy and tolerability of two doses of a fixed combination of 50 mg atenolol and 20 mg nifedipine slow release (1 capsule or 2 capsules once daily) in 16 hypertensive patients, treated for 4 weeks with each dose. The results suggest that the combination exerted a greater antihypertensive effect at 3 hours compared with 24 to 28-hours post-dose. Demonstrable differences in resting blood pressure between the low and high dose of the combination occurred at the 3-hour but not at the 24 to 28-hour post-dose time point. This apparent difference was also evident under exercise conditions, although no significance between dose differences were demonstrable at either time point. Thus, it appears that any additional benefit in efficacy obtained with the higher dose is not sustained over a 24-hours period. Side-effects were relatively uncommon with the combination, occurring least commonly with the lower dose. PMID- 2202548 TI - Single dose therapy of vaginal candidiasis: a comparative trial of fenticonazole vaginal ovules versus clotrimazole vaginal tablets. AB - An open, randomized comparative clinical trial was performed in 153 patients suffering from symptomatic vaginal candidiasis confirmed by mycological tests. Patients were allocated at random into two groups: the first group (consisting of 75 subjects) was treated with a single vaginal ovule of fenticonazole (600 mg) and the second group (consisting of 78 subjects) was treated with a single vaginal tablet of clotrimazole (500 mg). Therapeutic efficacy was assessed by microbiological and clinical criteria 7 days and 1 month (when possible) after the single dose treatment. At the first follow-up visit, complete disappearance of the signs and symptoms or a highly significant reduction of their intensity was observed in both treatment groups. No significant difference was evident between the two drugs. At 7 days, the mycological tests gave negative results in 92% of the patients in the fenticonazole group and in 88.5% of the patients in the clotrimazole group. The difference between the two treatment groups was again not statistically significant. The second follow-up visit was performed in 55 (73.3%) patients of the fenticonazole group and in 52 (66.7%) patients of the clotrimazole group. The results indicate that 83.6% of patients in the fenticonazole group and 69.2% of patients in the clotrimazole group were still disease free at the time of this visit. Both drugs were well tolerated. Mild, local and short lasting side-effects were reported in only 5 cases of the group treated with fenticonazole.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2202549 TI - A comparison of two formulations of indomethacin ('Flexin Continus' tablets and 'Indocid' capsules) in the treatment of rheumatoid arthritis. AB - A multi-centre, double-blind, crossover study was carried out in 80 patients with rheumatoid arthritis to compare the efficacy and side-effect profiles of two formulations of indomethacin. Patients were allocated at random to receive 75 mg indomethacin per day either as 1 controlled-release tablet at night or as 1 immediate-release capsule given 3-times a day for a period of 4 weeks before being crossed over to receive the alternative treatment for a further 4 weeks. Pain scores, daily symptomatology and the requirement for escape analgesia recorded by both investigator and patient indicated that controlled-release indomethacin tablets, 75 mg given at night, was as efficacous as immediate release indomethacin capsules given 3-times daily. However, the controlled release formulation had a superior side-effect profile with a reduced incidence of abdominal/epigastric pain compared to the immediate-release preparation. PMID- 2202550 TI - A comparison of two formulations of indomethacin ('Flexin Continus' tablets and 'Indocid' capsules) in the treatment of osteoarthritis. AB - The efficacy and side-effect profiles of two formulations of indomethacin were compared in a multi-centre, double-blind, crossover study in 77 patients with osteoarthritis. Patients were allocated at random to receive 75 mg indomethacin per day either as 1 controlled-release tablet at night or as 1 immediate-release capsule given 3-times daily for a period of 4 weeks, after which patients were crossed over to receive the alternative treatment for a further 4 weeks. Pain scores, daily symptomatology and the requirement for escape analgesia recorded by the investigator and patient indicate that controlled-release indomethacin tablets, 75 mg given at night, were as efficacious as immediate-release indomethacin capsules, 25 mg given 3-times daily, in the treatment of osteoarthritis. The side-effect profiles of the two formulations were similar. PMID- 2202551 TI - A comparison of choline magnesium trisalicylate and acetylsalicylic acid in patients with rheumatoid arthritis. AB - Choline magnesium trisalicylate (3.0 g/day) and enteric-coated acetylsalicylic acid (3.0 g/day) have been compared in a double-blind, crossover study on 19 patients with rheumatoid arthritis using the double-dummy technique. Patients were allocated to receive 3-weeks' treatment with each trial drug in random sequence and were assessed at Weeks-1, 0, 3 and 6. Apart from an unexplained significant improvement in grip strength (p less than 0.01) that occurred in patients on choline magnesium trisalicylate when this followed aspirin but not when it preceded it, there was no significant clinical difference between treatments in any of the clinical parameters of improvement that were measured. There was also no clear difference in the side-effects profile produced by the two drugs, but the number of patients recruited to this study was small. PMID- 2202552 TI - A comparison of flurbiprofen and naproxen in the treatment of rheumatoid arthritis: a Canadian multi-centre study. AB - A 6-week double-blind, parallel controlled, randomized study was carried out to compare the efficacy and tolerability of 100 mg flurbiprofen twice daily with 375 mg naproxen twice daily in patients with rheumatoid arthritis. One hundred and six patients from five centres were evaluable; 52 from the flurbiprofen group and 54 from the naproxen group. Evaluation of the primary efficacy parameters demonstrated no difference in efficacy between the treatment groups. In general, the results of evaluation of the secondary efficacy parameters also supported similar improvement for both treatment groups. The overall incidence of adverse clinical/laboratory experiences was similar between the treatment groups. Five patients, 3 flurbiprofen and 2 naproxen-treated, discontinued the study, all because of gastro-intestinal intolerance. PMID- 2202553 TI - Clinical evaluation of niflumic acid gel in the treatment of uncomplicated ankle sprains. AB - A double-blind, placebo-controlled, multi-centre study was carried out to assess the efficacy and tolerability of percutaneous niflumic acid gel in the treatment of uncomplicated ankle sprains. Sixty patients were enrolled in three centres and were randomly allocated to receive treatment with 2.5% percutaneous niflumic acid gel or placebo gel applied 3-times daily for 7 days. Clinical evaluations were made on entry to the study, after 3 days and at the end of treatment. The major efficacy criteria were the pain felt by the patient and the investigators' and patients' global evaluation of effectiveness of the treatment. Adverse events that occurred were also noted. The results showed that topically applied 2.5% niflumic acid gel was superior to placebo in the treatment of ankle sprains in respect of all major parameters studied. Niflumic acid gel and the placebo were shown to be equally well tolerated. The study findings indicate that treatment with topical niflumic acid gel is effective in treating uncomplicated ankle sprains and results in improved clinical signs on Day 4 and after 7 days. PMID- 2202554 TI - Anal carcinoma. AB - Although epidermoid cancer of the anus is an uncommon tumor, it has served well as a model for several disciplines within oncology. Advances in understanding the epidemiology and the definitive therapeutic role of combined radiation therapy and chemotherapy for anal tumors have encouraged many investigators to study similar applications in the more common epithelial malignancies. In this monograph, the anatomy of the anal area is reviewed emphasizing the differences in natural history and prognosis between anal margin and anal canal cancers. Treatment does not depend on the specific histologic variant of the epidermoid tumors which arise in this region. The roles of viruses, of immunodeficiency syndromes, and of a history of benign anal disease and trauma in the etiology and epidemiology of this tumor are discussed. Current staging will be critically reviewed stressing that invasive (pathologic) staging by surgery is not indicated, but noninvasive staging has definite limitations. Small superficial tumors may be definitively treated with either limited surgery or radiation. While regional treatments such as surgery and radiation offer cure to between 45% and 60% of nonselected patients, initial treatment with combination radiation and chemotherapy produces cure rates between 65% and 85% for similar groups of patients. The rationale for combined modality therapy is presented and recommendations for therapy by stage of the cancer are made. Finally, we present questions that remain for future research in the clinic and laboratory regarding epidermoid tumors of the anus. PMID- 2202555 TI - Diagnostic imaging of fertility disorders. AB - It is estimated that as many as 15% of married couples are affected by fertility disorders. The number of such couples seeking medical help has increased dramatically in the past 10 years due to both relative and absolute factors. The increase in population, the rising rate of sexually transmitted diseases, and the reduced availability of adoptable infants all contribute to the magnitude of this problem. The role of diagnostic imaging in the effective and compassionate care of couples desiring offspring is the subject of this review. Infertility is a disorder of a couple, not of two individuals. The diagnostic evaluation, therefore, must include both partners. Hysterosalpingography and ultrasound constitute the mainstay of the evaluation of the female member. The various techniques and complications of hysterosalpingography are reviewed. The normal appearance of the uterine cavity together with a review of the numerous anomalies and variations that might be encountered are presented. Along similar lines, the possible filling defects, synechiae, postoperative changes, and other alterations that may be encountered in imaging the uterine cavity are described. Evaluation of the fallopian tubes is of paramount importance, primarily to assess patency but also to assess the possibility of patent but diseased salpinges or disease of the surrounding peritubal tissue. Recently, interventional techniques using radiographic and sonographic control have been developed and are beginning to demonstrate promising results in the management of fallopian tube obstruction. These procedures, adapted from previously established radiographic interventive techniques, are discussed. The role of diagnostic imaging of the male partner is of lesser magnitude. Clinical assessment and semen evaluation generally permit adequate assessment of the male factor. Occasionally, however, vasography and seminal vesiculography are called into play. More frequently, sonographic evaluation to establish the presence of varicoceles is necessary. Such techniques are reviewed, as well as the interventional approaches for ablating varicoceles. The application of conventional and transvaginal sonography in the management of gynecologic fertility disorders is reviewed. Follicular monitoring, guided follicle aspiration, assessment of the status of the endometrium, guided embryo transfer and tubal cannulation, and evaluation of other pelvic disorders are significant factors in the appropriate management of the infertile couple.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2202556 TI - Dysphagia after laryngeal surgery: radiologic assessment. PMID- 2202558 TI - Development and dissemination of an aspiration risk reduction diet. AB - Patients with oropharyngeal swallowing disorders secondary to neurologic impairments benefit from diets that minimize the risk of aspiration. An aspiration risk reduction diet was developed from our hospital's regular menu cycle. Examples of the diet's preparation, dissemination, and use in a 600-bed acute medical/surgical teaching hospital are discussed. PMID- 2202559 TI - [A method of evaluating self-monitoring at home during pregnancy]. AB - All women of 30 gestational weeks in six hospitals in Shanghai during the period from January 1 to December 31 1987, were systematically and randomly divided into a study group of 6,506 for Self-Monitoring at home and a control group of 6,500. The observations showed that: the perinatal mortality rate was 6.30% in the study group and 10.92% in the control group; the fetal death rate was 3.23% and 6.34% respectively. The difference between the rates of the 2 groups was of statistical significance. The acceptability of this study was 92.5%. The above results suggested that self-monitoring at home during pregnancy is a simple, convenient and inexpensive method which does not require costly or precision instrument. It is also a relatively efficient method for mass screening of intrauterine fetal asphyxia, especially important for high risk pregnant women. PMID- 2202560 TI - [A transvaginal sonographic needle-guided method of ovum pickup in a fertilization in vitro/embryo transfer program]. AB - Methods of ovum pickup in the IVF/ET program in our hospital from January 1st 1988 to January 31st 1989, were reported. In the initial stage of the program in 1987, laparotomy follicle aspiration was used, which resulted in two cases of clinical pregnancy and full term delivery. Ovum pickup using an ultrasonic endovaginal transducer with a needle guide was introduced in the latter part of 1987. In 1988, the transvaginal method was employed more frequently than the laparotomy and has since become the routine in our program. The rate of embryo transfer and the average number of embryos transferred were quite similar in the two groups. Either method was adopted at that time according to the facilities available and the characteristic pathological conditions of our patients, of whom most had previous history of operation resulting in severe pelvic adhesions. The transvaginal ultrasonic needle guided method for egg retrieval is non-invasive, readily accepted by the patients and therefore may be done repeatedly on one patient in order to increase the cumulative pregnancy rate. However, the laparotomy (transabdominal) route for ovum pickup together with other pelvic surgeries is still indicated in some cases. The clinical pregnancy rate per transfer showed no statistical difference between the two groups. PMID- 2202561 TI - [Fetal Doppler echocardiography]. PMID- 2202562 TI - [The concept of pathologic drunkenness and diagnosis]. PMID- 2202563 TI - [Current research on seasonal affective disorder]. PMID- 2202564 TI - [Fragile X syndrome]. PMID- 2202565 TI - [Advances in immunologic research on inflammatory demyelinating polyneuropathy]. PMID- 2202557 TI - Central neural control of esophageal motility: a review. AB - We review recent studies on the central neural control of esophageal motility, emphasizing the anatomy and chemical coding of esophageal pathways in the spinal cord and medulla. Sympathetic innervation of the proximal esophagus is derived primarily from cervical and upper thoracic paravertebral ganglia, whereas that of the lower esophageal sphincter and proximal stomach is derived from the celiac ganglion. In addition to noradrenaline, many sympathetic fibers in the esophagus contain neuropeptide Y (NPY), and both noradrenaline and NPY appear to decrease blood flow and motility. Preganglionic neurons innervating the cervical and upper thoracic ganglia are located at lower cervical and upper thoracic spinal levels. The preganglionic innervation of the celiac ganglion arises from lower thoracic spinal levels. Both acetylcholine (ACh) and enkephalin (ENK) have been localized in sympathetic preganglionic neurons, and it has been suggested that ENK acts to pre-synaptically inhibit ganglionic transmission. Spinal afferents from the esophagus are few, but have been described in lower cervical and thoracic dorsal root ganglia. A significant percentage contain calcitonin gene-related peptide (CGRP) and substance P (SP). The central distribution of spinal afferents, as well as their subsequent processing within the spinal cord, have not been addressed. Medullary afferents arise from the nodose ganglion and terminate peripherally both in myenteric ganglia, where they have been postulated to act as tension receptors, and, to a lesser extent, in more superficial layers. Centrally, these afferents appear to end in a discrete part of the nucleus of the solitary tract (NTS) termed the central subnucleus. The transmitter specificity of the majority of these afferents remains unknown. The central subnucleus, in turn, sends a dense and topographically discrete projection to esophageal motor neurons in the rostral portion of the nucleus ambiguous (NA). Both somatostatin (SS) and ENK-related peptides have been localized in this pathway. Finally, motor neurons from the rostral NA innervate striated portions of the esophagus. In addition to ACh, these esophageal motor neurons contain CGRP, galanin (GAL), N acetylaspartylglutamate (NAAG), and brain natriuretic peptide (BNP). The physiological effect of these peptides on esophageal motility remains unclear. Medullary control of smooth muscle portions of the esophagus have not been thoroughly investigated. PMID- 2202566 TI - Cecal volvulus. AB - A review of 561 cases of cecal volvulus that were published between 1959 and 1989 along with 7 new cases, was performed to characterize the clinical and laboratory profile and to evaluate the various surgical options in treating this life threatening condition. The age and sex distribution of these patients have changed over the years and shifted toward older patients (mean, 53 years) and female predominance (female:male ratio, 1.4:1). The clinical presentation was usually of distal closed-loop small bowel obstruction. Forty-six percent of the plain abdominal radiographs were suspected for cecal volvulus, but only 17 percent were diagnostic. Barium enema had a high rate of accuracy (88 percent) and was associated with minimal complications. True volvulus was 6 times more common than bascule, and gangrenous cecum was found in 20 percent of cases. Detorsion alone and cecopexy had almost similar complications, mortality, and recurrence rates (15, 10, and 13 percent, respectively), whereas, resection, which was performed primarily for gangrenous cecum, had higher rates. However, the highest rates of complications (52 percent), mortality (22 percent), and recurrence (14 percent) were noticed after cecostomy. These data suggest that resection should be reserved for patients with necrotic cecum and that detorsion is sufficient for patients with viable cecum. Cecostomy should be abandoned. PMID- 2202567 TI - Cholelithiasis in inflammatory bowel disease. A case-control study. AB - Cholelithiasis is considered an extraintestinal manifestation of Crohn's ileitis but has not been associated with ulcerative colitis. To evaluate if an increased risk of cholelithiasis exists in patients with ulcerative colitis, biliary ultrasonography was performed on 159 patients with inflammatory bowel disease, 114 patients with ulcerative colitis, and 45 patients with Crohn's disease. A control population of 2453 residents of the town near the authors' institute was also studied. An echographic survey of gallstones was performed on the control subjects, who participated in the Multicentrica Italiana Colelitiasi (MICOL). Seventeen patients with inflammatory bowel disease had gallstones (10.7 percent), 11 patients with ulcerative colitis had gallstones (9.6 percent), and 6 patients with Crohn's disease had gallstones (13.3 percent). In the control population, diagnosis of cholelithiasis was made in 239 subjects (9.7 percent). An estimate of the relative risk (odds ratio) of gallstones in ulcerative colitis and Crohn's disease and also in 4 subgroups formed on the basis of the extent of disease (total ulcerative colitis, partial ulcerative colitis, Crohn's disease with ileitis, Crohn's disease without ileitis) with respect to the general population was calculated using logistic regression with gallstones, sex, age, and body mass index as independent variables and inflammatory bowel disease as a dependent variable. The author's findings show an increased risk of gallstones in both patients with Crohn's disease (odds ratio = 3.6; 95 percent confidence limits = 1.2 - 10.4; P = 0.02) and patients with ulcerative colitis (odds ratio = 2.5; 95 percent confidence limits = 1.2 - 5.2; P = 0.01). The risk was highest in patients with Crohn's disease involving the distal ileum (odds ratio = 4.5; 95 percent confidence limits = 1.5 - 14.1; P = 0.009) and in patients with total ulcerative colitis extending to the cecum (odds ratio = 3.3; 95 percent confidence limits = 1.3 - 8.6; P = 0.01). These results confirm that there is an increased risk of gallstones in Crohn's ileitis but they show that there also exists an increased risk in patients with total ulcerative colitis. PMID- 2202569 TI - A new type of ileostomy for chronic ulcerative colitis. 1939. PMID- 2202568 TI - Current status--perianal and anal canal neoplasms. AB - A large variety of neoplasms are found in the anal canal and perianal region. Most are distinctly uncommon and may, therefore, pose the question of suitable therapy. For some neoplasms, the treatment of choice is clear cut, while for others it is controversial. Certainly for squamous cell carcinoma of the anal canal, there has been a major rethinking of the treatment of choice. This review highlights the types of lesions found in the anal region and the current status regarding their appropriate treatment. PMID- 2202570 TI - Neurohumoral control of gallbladder motility in healthy subjects and diabetic patients with or without autonomic neuropathy. AB - Patients affected by diabetes mellitus are reported to have an increased incidence of gallbladder abnormalities. The pathophysiologic mechanisms for this phenomenon are unclear. In the present study ultrasonography was used to determine gallbladder emptying in response to a meal or separate cephalic or hormonal stimulation in 21 diabetic patients and 10 healthy subjects. Gallbladder emptying and refilling after a meal were similar in diabetic patients and healthy subjects. When diabetics were divided according to the presence or absence of cardiac autonomic neuropathy (AN), a significant reduction of gallbladder emptying in response to cephalic stimulation was found in diabetics with AN (P less than 0.01 in comparison with diabetics without AN or healthy subjects). A dose-response curve of gallbladder emptying in response cerulein, a cholecystokinin analog, at concentrations of 0.25, 1, and 4 micrograms/kg/min was evaluated. No differences of gallbladder emptying were found in the three groups of subjects, indicating that gallbladder sensitivity to hormonal stimulation is not changed in diabetic patients with or without AN. Diabetic patients with AN have a significant reduction of gastric acid output and pancreatic polypeptide (PP) secretion in response to cephalic stimulation (P less than 0.05 in comparison with diabetic patients without AN or healthy subjects). Cerulein induced PP secretion was similar in all three groups of subjects (P greater than 0.05). This study indicates that in diabetic patients with AN, gallbladder emptying as well as gastric acid and PP secretions induced by neural stimulation are markedly reduced in comparison to diabetics without AN. PMID- 2202571 TI - Dopamine in gastrointestinal disease. AB - Dopamine is an important enteric neuromodulator. Herein we review the data that support a role for dopaminergic involvement in experimental duodenal and gastric ulceration; gastric, pancreatic, and duodenal secretion; gastrointestinal motility; and gastric and intestinal submucosal blood flow regulation. There also is support for a role for dopamine and dopamimetic agents in the treatment of certain experimental gastrointestinal diseases because some highly selective dopamine agonists are gastroprotective when given either parenterally or centrally. Based upon these observations, we suggest that dopamine is a key element of the "brain-gut axis" and represents a potentially important target for pharmacotherapeutic exploitation. PMID- 2202572 TI - Mixing insulins in 1990. AB - Lente insulins can be mixed in any ratio at any time. Regular plus NPH insulins seem to be the preferred mixture of rapid- and intermediate-acting insulins because the effect of the combined insulins is the same as that of regular and NPH insulin injected separately. Mixing regular with lente insulins is more complex and needs further study. However, at the present time, if regular and lente insulins are going to be mixed, they should be either mixed and injected immediately, or they should be left to interact for up to 24 hours, in which case the resultant mixture does not have as rapid an action as the immediately injected mixture. Combinations of regular and protamine zinc insulins are rare and complicated by the fact that the resultant product is based upon the ratios of regular to PZI. Generally speaking, protamine zinc insulin is rarely used in humans. It is used by some veterinarians, especially to treat cats with diabetes. The Table summarizes information concerning the mixing of various insulins. PMID- 2202573 TI - Approach to management. AB - This paper describes a physiologic approach to diabetes management called pattern therapy and compares it with the sliding scale or "catch-up" type of management. Pattern therapy differs from the sliding scale approach in that it anticipates rather than reflects insulin needs, and it relies heavily on intensive patient education and intelligent self-management. Frequent blood glucose monitoring is also a key aspect of pattern therapy. PMID- 2202575 TI - [Hemolytic-uremic syndrome in an adult with T-cryptantigen liberation]. AB - Haemolytic uraemic syndrome was diagnosed in a 36-year-old woman with acute renal failure (creatinine 10.5 mg/dl), haemolytic anaemia (haemoglobin 9.7 g/dl, lactate dehydrogenase 1926 U/l) and thrombopenia (98,000/microliters). After initial plasmaphereses and high doses of furosemide all symptoms disappeared within three weeks. The lectin tests demonstrated that the illness was connected with the liberation of T-crypt-antigen (Thomsen-Friedenreich antigen) on the erythrocytes. This special form of the haemolytic uraemic syndrome (neuraminidase induced haemolytic uraemic syndrome) has previously been observed almost exclusively in children. However, for diagnosis and differentiation of haemolytic uraemic syndromes the presence of liberated T-antigen on erythrocytes should also be tested for in adults. PMID- 2202576 TI - [Demonstration and identification of fungi in dermatomycoses]. PMID- 2202574 TI - Review of present and future use of nonnutritive sweeteners. AB - In response to growing consumer demand for better tasting, low-calorie, sugar free food products, the number of food items containing nonnutritive sweeteners has grown markedly in recent years. In this paper, present sweetener consumption is reviewed; the history, properties, uses, advantages, and safety of approved sweeteners such as saccharin, aspartame, and acesulfame-K are presented, as well as those of sweeteners such as cyclamate, sucralose, and alitame that are awaiting FDA approval; the role of sweeteners in the dietary management of persons with diabetes is discussed; and counseling guidelines for safe consumption are given. PMID- 2202577 TI - [Treatment of dermatomycoses]. PMID- 2202578 TI - [Toxic encephalopathy as an occupational disease]. PMID- 2202579 TI - [Myocardial rupture after myocardial infarct]. PMID- 2202580 TI - [Antihypertensive treatment in kidney diseases: whom, with what, how intensively?]. PMID- 2202583 TI - Effects of drugs on glucose tolerance in non-insulin-dependent diabetics (Part I). AB - Non-insulin-dependent diabetes mellitus (NIDDM) is being increasingly diagnosed as its importance as a risk factor for the development of cardiovascular disease continues to be recognised. Good metabolic control remains a major goal of drug therapy as it decreases the severity and incidence of diabetic complications. Many drugs have been known to interfere with glucose control, either in a beneficial or, more commonly, in a deleterious fashion. Unfortunately in many instances drug-induced effects have not been looked at specifically in NIDDM. Thiazide diuretics have been shown to cause a deterioration in glucose control not only in the general population but especially in patients who have impaired glucose tolerance. While the effect appears less with potassium supplementation and the lower dosage employed nowadays, thiazide diuretics are best avoided in diabetic patients. Loop diuretics have been reported to reduce glucose control to a lesser extent than thiazides. Although indapamide would appear not to interfere with blood sugar control in NIDDM, higher doses that cause potassium loss may cause a deterioration. beta-Adrenoceptor antagonists have been reported to cause a rise in blood sugar and glycosylated haemoglobin in NIDDM. The effect may be more marked in patients on oral hypoglycaemic agents as opposed to diet alone and in those on concomitant thiazide diuretics. The greatest effect was seen with propranolol, and the least with cardioselective and the less lipophilic beta blockers. It is of interest that alpha-blockade with prazosin seems to antagonise beta-adrenoceptor blocker-induced deterioration in glucose control. The calcium antagonists have differing effects which may be structure related. In some, but not all, studies use of the dihydropyridines such as nifedipine has been associated with a deterioration in glucose control in NIDDM. Long term studies are needed to assess definitively their effect on glucose control. Verapamil, on the other hand, has in 1 small study been found to have a beneficial effect on glucose control in NIDDM. Centrally acting alpha-agonists such as the antihypertensive drug clonidine have not been shown to result in a deterioration in glucose control when used in NIDDM, although there are isolated case reports. Long term therapy with the more specific agonist guanfacine was reported in 1 uncontrolled study to have a beneficial effect on glucose tolerance in NIDDM. Uncontrolled studies suggest that phenothiazines may aggravate diabetic control. The significance of a number of recent observations is not fully clear.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2202582 TI - Current treatment recommendations for lupus nephritis. AB - Renal disease is common in patients with systemic lupus erythematosus and may run an extremely variable course. Specific therapy is not necessary in patients with mild kidney involvement but a careful surveillance is needed to recognise possible transformations to more severe disease classifications or flare-ups. Vigorous treatment must be started early in patients with nephritic syndrome and/or active lesions at renal biopsy, i.e. glomerular cell proliferation, necrosis and inflammation. Corticosteroids remain the cornerstone for treating lupus nephritis. However, every attempt should be made to minimise their possible toxic effects. A short course of intravenous high-dose methylprednisolone followed by moderate doses of prednisone is a relatively nontoxic regimen which is generally effective in reversing the flare-ups of the disease. Once the activity is quenched the maintenance dosage of steroids should be reduced to the lowest possible dose, trying to switch the patient to an alternate-day regimen whenever possible. In patients with persisting activity the administration of a cytotoxic agent may obviate the need for protracted high-dose corticotherapy. Intermittent intravenous cyclophosphamide pulses may be considered in nonresponding patients. Other approaches, with cyclosporin, lymphoid irradiation, etc. although promising, are still preliminary. Although we are still far from an optimal treatment of lupus nephritis, the refined use of corticosteroid and cytotoxic agents and a careful monitoring of patients may allow excellent patient and kidney survival rates for 10 or more years. PMID- 2202581 TI - Moricizine. A review of its pharmacological properties, and therapeutic efficacy in cardiac arrhythmias. AB - Moricizine (moracizine, ethmozine) is an orally active phenothiazine derivative with direct myocardial Class I antiarrhythmic activity and minimal CNS effects. Placebo-controlled studies have confirmed its efficacy in suppressing nonmalignant ventricular arrhythmias (premature ventricular complexes, couplets and runs of nonsustained ventricular tachycardia), including those refractory to previous antiarrhythmic therapy. Preliminary findings have indicated that moricizine is also effective in suppressing atrial ectopic activity, atrioventricular nodal re-entry tachycardia and Wolff-Parkinson-White tachycardias involving accessory pathways. As with other oral antiarrhythmics, malignant ventricular arrhythmias (sustained ventricular tachycardia and ventricular fibrillation) have been shown, both on noninvasive monitoring and programmed electrical stimulation, to be less susceptible to suppression by moricizine than nonmalignant ventricular arrhythmias. The therapeutic potential of moricizine is enhanced by its relatively low incidence of extra-cardiac adverse effects (predominantly gastrointestinal and neurological) and its lack of significant cardiodepressant activity in patients with normal or mildly to moderality depressed left ventricular function. Moricizine has proved to be more effective than disopyramide and propranolol in suppressing ventricular ectopic activity, of comparable efficacy to quinidine, but less effective than encainide and flecainide. The drug appears to be particularly suited to the suppression of ventricular ectopy in patients with preexisting left ventricular dysfunction. Further studies are required to confirm its long term efficacy and effects on mortality when used prophylactically in patients at increased risk of sudden cardiac death. PMID- 2202584 TI - Ocular betaxolol. A review of its pharmacological properties, and therapeutic efficacy in glaucoma and ocular hypertension. AB - Betaxolol is a lipophilic beta-adrenoceptor antagonist relatively selective for beta 1-adrenoceptors with only weak beta 2-blocking activity. Used topically in glaucoma and ocular hypertension, betaxolol 0.5% solution produces a reduction in intraocular pressure of between 13 and 30%, an effect comparable with that of ocular timolol. It may usefully be combined with other types of anti-glaucoma agents. The most notable feature of its adverse effect profile is transient local stinging or irritation, occurring in 25 to 40% of patients. Following ocular administration, betaxolol appears to be largely devoid of adverse bronchopulmonary or cardiac effects, in comparison with nonselective ocular beta adrenoceptor antagonists, which may be more likely to exert systemic effects. Betaxolol has negligible local anaesthetic activity, so that corneal desensitisation does not occur with its use. Thus, betaxolol is an alternative therapeutic option available to the physician for the management of chronic open angle glaucoma and ocular hypertension. Its apparently lower propensity to affect the cardiopulmonary system represents a significant advantage over other ocular beta-adrenoceptor antagonists. PMID- 2202586 TI - Efficacies of chloroquine and pyrimethamine-sulphadoxine in a Nigerian population with chloroquine resistant P. falciparum malaria. AB - A modification of the standard World Health Organisation 7--day in vivo test was used to assess the parasitologic and, to limited extent, the clinical response of children less than 5 years of age to defined oral dosages of chloroquine and pyrimethamine-sulphadoxine during the 14 days following the initiation of treatment. The study took place in Jato-Aka, a rural community in Benue State of Nigeria. 471 children were screened and 271 (59%) of these had plasmodium parasites thus showing a high transmission rate at a time of the year with scarce rainfall. Of the 42 children on chloroquine and who were followed up to day 2, 4 or 9.5% of them were parasitologic failures while none of the 45 children on pyrimethamine-sulphadoxine (P-S) failed parasitologically. By day 7, 21 (50%) of the children on chloroquine and 4 or 8.9% of those on P-S. had become parasitologic failures. The total number of parasitologic failures on day 14 were 21 (50%) and 4(8.9%) for chloroquine and P-S groups respectively. Chloroquine improved the clinical state of the patients better than P-S. However, P-S appears superior in clearing the parasites. These results confirm the existence of both chloroquine and pyrimethamine-sulphadoxine resistant strains of P. falciparum in some regions of Nigeria. The routine chloroquine chemoprophylaxis of children under 5 years of age should be discontinued so as not to hasten the intensification of chloroquine resistance and because of its probable marginal efficacy at chemoprophylaxis dosages. There is also need for a national policy on pyrimethamine-sulphadoxine usage in order not to hasten its resistance to P. falciparum. PMID- 2202587 TI - The in vitro response of Plasmodium falciparum to amodiaquine, quinine and quinidine in Tanga region, Tanzania. AB - The in vitro response of P. falciparum to amodiaquine, quinine and quinidine was assessed in Tanga region where chloroquine resistance is established, to determine baseline susceptibility levels which could guide health care deliverers on the suitability of these drugs for the treatment of falciparum malaria in the areas studied. Amodiaquine resistance was observed in all of the three areas. 16.7%, 24.0% and 14.7% of successful in vitro tests showed resistance to amodiaquine in Korogwe, Muheza and Tanga respectively. The in vitro response to quinine and quinidine showed that P. falciparum strains in the three areas are very sensitive to the two drugs. Only 1.9%, 4.5% and 1.4% of successful quinine tests showed resitance in Korogwe, Muheza and Tanga respectively. Quinidine showed activity which is twice higher than that of quinine and only 1 isolate in Tanga showed resistance response to quinidine. PMID- 2202588 TI - Similarities in the microfloras of root canals and deep periodontal pockets. AB - Although not universally accepted, retrospective histological, roentgenological and microbiological studies have indicated that cross-infection can occur between infected pulps and deep periodontal pockets. This review provides examples of similarities in the microfloras of these adjacent oral sites, supporting the idea that infection spreads from one site to the other. The organisms most often involved are probably bacteroides, fusobacteria, eubacteria, spirochetes, wolinellas, selenomonas, campylobacter, and peptostreptococci. Important qualities of cross-infecting organisms may be the ability to survive in highly reduced environments and motility. Precautions should be taken to prevent in vivo seeding of such micro-organisms, particularly in compromised teeth and hosts. PMID- 2202589 TI - Some observations on the mechanics of oscillation of ultrasonic files. AB - The resonant characteristics of ultrasonic files driven by the Cavi-Endo unit were examined. The investigation was carried out by evaluating the pattern of oscillation and the power emitted by the ultrasonic files. It was observed that the files oscillated in a sinusoidal fashion, exhibiting a standing wave pattern along the file. The power emitted was found to be directly proportional to the flexibility of the file. Such behaviour is typical of a system that exhibits resonance. PMID- 2202590 TI - Image analysis of endodontic radiographs: digital subtraction and quantitative densitometry. AB - In this study computerized image analysis procedures were applied to endodontic radiographs. Kontron IBAS 2000 is a commercially available image analysis system with processing routines applicable to radiograph digitizing and transformations. The system was evaluated for: its ability to harmonize blackening and contrast in endodontic radiographs; its ability to compensate for angulation distortion of sequential exposures of individual teeth; its potential for application of digital subtraction methods; and its use in automated gray-level analyses of diseased and healthy bone areas in endodontic radiographs. The Kontron IBAS 2000 system proved suitable for all applications. However, the specificity of the subtraction procedure was limited by some inherent problems in the harmonization of blackening and in the subtraction process itself. On the other hand, automated gray level measurements proved to be a robust method for unbiased and quantitative assessment of healing of apical periodontitis. PMID- 2202591 TI - Mapping of catalytically important domains in Escherichia coli leader peptidase. AB - Leader peptidase (Lep) is a central component of the secretory machinery of Escherichia coli, where it serves to remove signal peptides from secretory proteins. It spans the inner membrane twice with a large C-terminal domain protruding into the periplasmic space. To investigate the importance of the different structural domains for the catalytic activity, we have studied the effects of a large panel of Lep mutants on the processing of signal peptides, both in vivo and in vitro. Our data suggest that the first transmembrane and cytoplasmic regions are not directly involved in catalysis, but that the second transmembrane region and the region immediately following it may be in contact with the signal peptide and/or located spatially close to the active site of Lep. PMID- 2202592 TI - Initial steps in protein membrane insertion. Bacteriophage M13 procoat protein binds to the membrane surface by electrostatic interaction. AB - Bacteriophage M13 procoat protein is synthesized on free polysomes prior to its assembly into the inner membrane of Escherichia coli. As an initial step of the membrane insertion pathway, the precursor protein interacts with the cytoplasmic face of the inner membrane. We have used oligonucleotide-directed mutagenesis to study the regions of the procoat protein involved in membrane binding. We find that there is an absolute requirement for positively charged amino acids at both ends of the protein. Replacing these with negatively charged residues resulted in an accumulation of the precursor in the cytoplasm. We propose that the positively charged amino acids are directly involved in membrane binding, possibly directly to the negatively charged phospholipid head groups. This was tested in vitro with artificial liposomes. Whereas wild-type procoat interacted with these liposomes, we found that procoat mutants with negatively charged amino acids at both ends did not bind. Therefore, we conclude that newly synthesized M13 procoat protein binds electrostatically to the negatively charged inner membrane of E. coli. PMID- 2202585 TI - Naproxen. A reappraisal of its pharmacology, and therapeutic use in rheumatic diseases and pain states. AB - Naproxen is a nonsteroidal anti-inflammatory drug (NSAID) advocated for use in painful and inflammatory rheumatic and certain nonrheumatic conditions. It may be administered orally or rectally using a convenient once or twice daily regimen. Dosage adjustments are not usually required in the elderly or those with mild renal or hepatic impairment although it is probably prudent to start treatment at a low dosage and titrate upwards in such groups of patients. Numerous clinical trials have confirmed that the analgesic and anti-inflammatory efficacy of naproxen is equivalent to that of the many newer and established NSAIDs with which it has been compared. The drug is effective in many rheumatic diseases such as rheumatoid arthritis, osteoarthritis, ankylosing spondylitis and nonarticular rheumatism, in acute traumatic injury, and in the treatment of and prophylaxis against acute pain such as migraine, tension headache, postoperative pain, postpartum pain and pain associated with a variety of gynaecological procedures. Naproxen is also effective in treating the pain and associated symptoms of primary or secondary dysmenorrhoea, and decreases excessive blood loss in patients with menorrhagia. The adverse effect profile of naproxen is well established, particularly compared with that of many newer NSAIDs, and the drug is well tolerated. Thus, the efficacy and tolerability of naproxen have been clearly established over many years of clinical use, and it can therefore be considered as a first-line treatment for rheumatic diseases and various pain states. PMID- 2202594 TI - Differential repair of UV damage in Saccharomyces cerevisiae is cell cycle dependent. AB - In the yeast Saccharomyces cerevisiae the transcriptionally active MAT alpha locus is repaired preferentially to the inactive HML alpha locus after UV irradiation. Here we analysed the repair of both loci after irradiating yeast cells at different stages of the mitotic cell cycle. In all stages repair of the active MAT alpha locus occurs at a rate of 30% removal of dimers per hour after a UV dose of 60 J/m2. The inactive HML alpha is repaired as efficiently as MAT alpha following irradiation in G2 whereas repair of HML alpha is less efficient in the other stages. Thus differential repair is observed in G1 and S but not in G2. Apparently, in G2 a chromatin structure exists in which repair does not discriminate between transcriptionally active and inactive DNA or, alternatively, an additional repair mechanism might exist which is only operational during G2. PMID- 2202593 TI - Cleavages in the 5' region of the ompA and bla mRNA control stability: studies with an E. coli mutant altering mRNA stability and a novel endoribonuclease. AB - We describe here the partial purification of a novel Escherichia coli endoribonuclease, RNase K. This protein catalyses site-specific cleavages in the 5' region of in vitro transcribed ompA and bla transcripts. Some of the resulting cleavage products are also found in cellular ompA mRNA, defining the in vivo activity of RNase K. The following evidence suggests that RNase K initiates mRNA degradation. First, RNase K cleavages are suppressed in the ams mutant, which has a generally prolonged mRNA half-life. Secondly, RNase K cleavage products seem to have very short half-lives in vivo, indicating that they are decay intermediates rather than processing products. Thirdly, the differences in in vivo half-life between the ompA and bla mRNAs are mimicked in in vitro decay reactions with purified RNase K. The relationship between RNase K and the ams locus might point to a more general role of RNase K in mRNA degradation. We discuss the influence of mRNA secondary structure on RNase K cleavage specificity. PMID- 2202595 TI - Electromyographic evidence of selective fatigue during the eccentric phase of stretch/shortening cycles in man. AB - Ten male subjects were tested to determine the effects of muscle fatigue upon the activation pattern of the two main ankle extensor muscles, the 'slow-twitch' soleus (SOL) and the relatively 'fast-twitch' medial gastrocnemius (MG), during a fatiguing 60-s trial of hopping to maximal height. The myoelectric signals from SOL and MG were recorded together with the vertical ground reaction force signal and analysed by means of a computer-aided electromyograph (EMG) contour analysis, i.e. two-dimensional frequency distributions were obtained relating the activation patterns of the two synergists. The EMGs were also full-wave rectified and integrated (IEMG) according to three phases of the hopping movement (PRE, pre activation phase; ECC, eccentric phase; CON, concentric phase). Results indicated that there were significant decreases (P less than 0.01) in the peak ground reaction force, the height of hopping and the mechanical power per unit body weight at the end of the fatiguing contractions. These decreases in mechanical parameters were accompanied by significant (P less than 0.01) decreases in all three phases of MG IEMG while SOL IEMG showed no such significant declines, except in the CON phase. Thus, the decreased mechanical parameters could in large part be accounted for by the substantial and selective decline of the excitation level of the relatively fast-twitch MG muscle. Our data suggest that the centrally mediated pre-activation of the fatiguable MG muscle as well as the MG activation during the eccentric phase, which is largely controlled by supraspinal inputs and stretch-reflex modulation, are most affected by fatigue changes during repeated maximal stretch/shortening cycles of the ankle extensors. PMID- 2202597 TI - Expression in Escherichia coli of ferredoxin:NADP+ reductase from spinach. Bacterial synthesis of the holoflavoprotein and of an active enzyme form lacking the first 28 amino acid residues of the sequence. AB - A cDNA clone for the preprotein of spinach ferredoxin:NADP+ reductase has been modified to allow the expression in Escherichia coli of the mature flavoprotein form the lacks the transit peptide. An expression vector, pFNR1, was constructed by subcloning the fragment into the plasmid pDS12/RBSII, SphI. In the crude extracts of transformed cells after induction, two active holoproteins of 35 kDa and 32 kDa, respectively, were found. The 32-kDa protein, purified by immunoaffinity chromatography, was found to lack the first 28 residues of the spinach protein sequence and to have a methionine as the N-terminal residue instead of Val29. A new expression plasmid, pFNR2, was obtained by in vitro mutagenesis of the codon GTG for Val29 to the synonymous GTT; in this case, only the 35-kDa protein was expressed by transformed cells. Both the 35-kDa and 32-kDa enzymes were purified and characterized. All the properties analyzed of the cloned 35-kDa enzyme were very similar to those of the spinach flavoprotein. The 32-kDa form showed the same catalytic efficiency of the spinach enzyme as a diaphorase but its interaction with oxidized ferredoxin was partially impaired. PMID- 2202596 TI - The monitoring of the menstrual status of female athletes by salivary steroid determination and ultrasonography. AB - This study was designed to evaluate whether traditional plasma hormone determinations can be adequately replaced by measurements of salivary hormones. Eleven young sportswomen with menstrual irregularities attributed to strenuous physical exercise participated in this study. Mean body weight expressed as a percentage of ideal body weight was 92%, SD 4%. Their mean weekly training distance was 35 km, SD 15. Basal plasma endocrinological measurements revealed a hypo-oestrogenic status (mean plasma oestradiol values: 22 pg.ml-1, SD 8.8), and a deficient luteal phase (mean plasma progesterone: 2.9 ng.ml-1, SD 2.1). Pre exercise salivary sex steroids were low. Salivary progesterone levels were 39.3 pg.ml-1, SD 9.5 (normal ranges in saliva: 25-60 pg.ml-1), salivary oestrone (E1) was 12.2 pg.ml-1, SD 2.3 (normal ranges in saliva: 7.5-25 pg.ml-1), and salivary oestradiol (E2) less than 1.9 pg.ml-1, SD 1.1 (normally 1.0-10.0 pg.ml-1). After a 21-km run, all salivary steroids appeared to increase. Mean salivary testosterone levels increased by 15.2% and salivary progesterone by 14.8%. Mean salivary oestrogens also increased (E1: +13.9%; E2: +21.1%). These findings confirm the results of earlier studies which found higher post-exercise plasma sex steroid levels. Since salivary measurements are believed to reflect non protein-bound, thus free steroid levels, the results obtained by these techniques may provide a more realistic picture of the hormonal effects of physical exercise. In future, more accurate, cost-effective and easier techniques for salivary measurements may offer additional advantages. PMID- 2202598 TI - Effect of polyamines on the activity of malarial alpha-like DNA polymerase. AB - DNA polymerase from the malarial parasite Plasmodium falciparum required Mg2+ for activity, Putrescine (1 mM) caused a twofold increase in enzyme activity in the presence of a suboptimal concentration of MgCl2 (2 mM). Spermidine (1.5-2.0 mM) or spermine (0.1-0.3 mM) increased the activity of malarial DNA polymerase, in the presence of 2 mM MgCl2, by factors of 6 and 3-5, respectively. The activity of DNA polymerase from calf thymus or from NIH 3T3 cells transformed by the ras oncogene were not stimulated by these polyamines to the same extent. These findings suggest that in malaria-infected erythrocytes, polyamines, at physiological concentrations, serve as a cofactor for the parasitic alpha-like DNA polymerase. Malarial parasites grown in cultured human erythrocytes did not synthesize DNA after treatment with alpha-difluoromethylornithine, which caused polyamine depletion in the infected cells. DNA synthesis was resumed after adding putrescine to the polyamine-depleted cultures. DNA synthesis was also initiated when actinomycin D was added along with putrescine to polyamine-depleted cells. It thus appears that polyamines are essential for the translation of the DNA polymerase mRNA and that polyamines play an important role in regulating the cell cycle of the malarial parasite. PMID- 2202599 TI - Fructose-1,6-bisphosphate-activated pyruvate kinase from Escherichia coli. Nature of bonds involved in the allosteric mechanism. AB - The allosteric properties of the fructose-1,6-bis-phosphate-activated pyruvate kinase from Escherichia coli were examined in the presence of a number of fructose bisphosphate analogues, as well as of increased ionic strength (NaCl) and of the hydrogen-bond-breaking agent, formamide. Fructose 2,6-bisphosphate, ribulose 1,5-bisphosphate and 5-phosphorylribose 1-pyrophosphate gave allosteric activation (additive to that of fructose 1,6-bisphosphate). Formamide always decreased Vmax, but left unchanged the Km for phosphoenolpyruvate, while it decreased the concentration of fructose bisphosphate required to give half maximal activity (K0.5). NaCl increased the K0.5 for both phosphoenolpyruvate and fructose bisphosphate, leaving Vmax unchanged. These results are consistent with ionic binding of fructose bisphosphate through phosphates and with a critical role of hydrogen bonds in stabilizing both the inactive and the active enzyme conformers. PMID- 2202600 TI - Purification and characterisation of TOL plasmid-encoded benzyl alcohol dehydrogenase and benzaldehyde dehydrogenase of Pseudomonas putida. AB - Benzyl alcohol dehydrogenase and benzaldehyde dehydrogenase, two enzymes of the xylene degradative pathway encoded by the plasmid TOL of a Gram-negative bacterium Pseudomonas putida, were purified and characterized. Benzyl alcohol dehydrogenase catalyses the oxidation of benzyl alcohol to benzaldehyde with the concomitant reduction of NAD+; the reaction is reversible. Benzaldehyde dehydrogenase catalyses the oxidation of benzaldehyde to benzoic acid with the concomitant reduction of NAD+; the reaction is irreversible. Benzyl alcohol dehydrogenase and benzaldehyde dehydrogenase also catalyse the oxidation of many substituted benzyl alcohols and benzaldehydes, respectively, though they were not capable of oxidizing aliphatic alcohols and aldehydes. The apparent Km value of benzyl alcohol dehydrogenase for benzyl alcohol was 220 microM, while that of benzaldehyde dehydrogenase for benzaldehyde was 460 microM. Neither enzyme contained a prosthetic group such as FAD or FMN, and both enzymes were inactivated by SH-blocking agents such as N-ethylmaleimide. Both enzymes were dimers of identical subunits; the monomer of benzyl alcohol dehydrogenase has a mass of 42 kDa whereas that of the monomer of benzaldehyde dehydrogenase was 57 kDa. Both enzymes transfer hydride to the pro-R side of the prochiral C4 of the pyridine ring of NAD+. PMID- 2202602 TI - [Oral symptoms of denture wearers and the monomer content of the base plate]. AB - Out of 17 patients 15 cases showed mouth burning, and with 14 patients various types of mouth inflammations were found. By means of Microstix Candida test fungus was proved in 7 cases by means of gas chromatography free monomer content was in 16 dentures. The free monomer content of the autopolymerizing acrylics was between 0.04 and 1.06% (v/v). Mouth inflammation of the more grave diffuse and papillar type was not associated with higher concentration occurrence of the free monomer in the denture base plates. At the same time the causal connection in producing the clinical symptoms cannot be excluded in view of the presence of unbound metilmetacrylate monomer. PMID- 2202601 TI - Molecular cloning of the gene for the E1 alpha subunit of the pyruvate dehydrogenase complex from Saccharomyces cerevisiae. AB - The E1 alpha and E1 beta subunits of the pyruvate dehydrogenase complex from the yeast Saccharomyces cerevisiae were purified. Antibodies raised against these subunits were used to clone the corresponding genes from a genomic yeast DNA library in the expression vector lambda gt11. The gene encoding the E1 alpha subunit was unique and localized on a 1.7-kb HindIII fragment from chromosome V. The identify of the gene was confirmed in two ways. (a) Expression of the gene in Escherichia coli produced a protein that reacted with the anti-E1 alpha serum. (b) Gene replacement at the 1.7-kb HindIII fragment abolished both pyruvate dehydrogenase activity and the production of proteins reacting with anti-E1 alpha serum in haploid cells. In addition, the 1.7-kb HindIII fragment hybridized to a set of oligonucleotides derived from amino acid sequences from the N-terminal and central regions of the human E1 alpha peptide. We propose to call the gene encoding the E1 alpha subunit of the yeast pyruvate dehydrogenase complex PDA1. Screening of the lambda gt11 library using the anti-E1 beta serum resulted in the reisolation of the RAP1 gene, which was located on chromosome XIV. PMID- 2202603 TI - [Current viewpoints and methods in caries diagnosis]. AB - Results obtained in the caries pathogenesis in recent years as well as the successes in the field of remineralization opened the way to heal the initial stage of the caries by means of preventive methods. Increased attention should be paid to early diagnostics of the caries, and evolution of the new diagnostics methods should be followed by attention. Combined employment of the various diagnostics methods should be aimed at. PMID- 2202604 TI - Occurrence of nonlymphoid leukocytes that are not derived from blood islands in Xenopus laevis larvae. AB - Previous immunohistochemical observations using the monoclonal antibody (XL-1) which recognizes all types of leukocytes in Xenopus laevis revealed the occurrence of XL-1+ cells in the mesenchyme throughout the early larval body, before the appearance of any lymphocytes. The present experiments were performed to determine whether these leukocytes originate, like lymphocytes and red blood cells (RBCs), in the ventral blood islands (VBI) or the dorsolateral plate (DLP). For tracing the derivation of cells, a specific staining by quinacrine to nuclei of X. laevis and Xenopus borealis hybrid (LB) cells was used to distinguish them from X. laevis (LL) cells. Orthotopic graftings of VBI tissue from st.22-23 LB embryos to the stage-matched LL embryos and examinations at st.44-45 before differentiation of the lymphocytes showed that the proportion of XL-1+ LB cells was always significantly lower than that of RBCs with the same marker in all experimental larvae. The head (LB)-body (LL) chimeras from st.22-23 embryos and culture of the head-portions as VBI- and DLP-free explants from st.14-23 embryos both demonstrated that a significant number of XL-1+ cells which had originated in the head portions had begun to differentiate by st.42-43. These results indicate that there is a significant population of larval nonlymphoid leukocytes (mostly macrophages) that do not originate from either the VBI or DLP region, and are distributed in the mesenchyme throughout the body. PMID- 2202606 TI - Risk of seizures. PMID- 2202605 TI - Expression of fibronectin variants in vascular and visceral smooth muscle cells in development. AB - Monoclonal antibodies recognizing extra domain A (ED-A) and extra domain B (ED-B) fibronectin (FN) sequences were used to characterize FN variants expressed in human vascular smooth muscle cells (SMC) during fetal and postnatal development and to compare spectrum of FN variants produced by vascular and visceral SMC. In 8- to 12-week-old fetuses both ED-A-containing FN (A-FN) and ED-B-containing FN (B-FN) were found in all smooth muscles studied--aorta, esophagus, stomach, and jejunum. By 20-25 weeks of gestation relative amounts of both A-FN and B-FN were reduced significantly in the aortic media (fivefold for A-FN and twofold for B FN), while in visceral SMC only B-FN content was decreased. All the adult visceral smooth muscles examined contained A-FN rather than B-FN. Therefore, the cells from adult aortic media appear to be the only SMC so far known to produce FN that contains neither ED-A nor ED-B. Moreover, the data obtained show that, unlike other cells, medial SMC are embedded in vivo in the extracellular matrix that contains FN lacking both ED-A and ED-B. SMC from the minor intimal thickenings in the human child aorta as well as those from the atherosclerotic plaques produce A-FN rather than B-FN. We conclude that (1) vascular SMC change the spectrum of produced FN variants at least twice--during prenatal development between 12 and 20 weeks of gestation, and during the postnatal period, when they are recruited into the intimal cell population; (2) the production of FN variants in visceral SMC is also developmentally regulated; (3) all visceral SMC unlike the cells from adult aortic media produce A-FN; (4) the presence of ED-A and ED-B sequences in the FN molecule is not necessary for the extracellular matrix assembly in vivo. PMID- 2202607 TI - [Use of oral contraceptives in East Germany by middle-aged females]. AB - This study was based on the data from 1214 women included in the controlled group within a hospital-based case-control study on the association between breast cancer and the use of oral contraceptives. This is a sample of middle-aged women. Women with a reason for referral, presumably associated with infertility, were excluded. Oral contraceptives are (apart from coitus interruptus) in 76% of the cases the method of contraception most frequently used, followed by the rhythm method and condoms. The use depends strongly on the age. Only 40% of the women, now 55-60 years of age, ever used oral contraceptives, whereas 91% of those now under 40 have been using them. Other connections can be seen with level of education, marital status, and reproduction and sex life. With the use of special preparations, there are differences between women of younger and older generations, partially based on the different times these preparations were introduced to the market. The exclusive use of sequential oral contraceptives decreases in the older cases. PMID- 2202608 TI - [Clinical value of a decrease in diastolic flow in obstetric Doppler sonography]. AB - Doppler ultrasound in obstetrics is being increasingly accepted in foetal surveillance. For clinical practice, a good correlation between Doppler findings and biochemical data such as blood gas analysis and lactate as a metabolical parameter, would be desirable. To clarify this question, these results have to be compared. Prepartal Doppler results which are correlated with postpartal blood gas analyses of umbilical vessels cannot be a satisfactory criterion due to the influence of labour on these parameters. Therefore, we depend on results from foetal blood sampling procedure. The five cases presented here should be a contribution to this discussion. In summary it can be concluded, that in cases of a highly pathological Doppler analysis in the umbilical artery, intrauterine growth retardation must be expected. If there is an acidosis in the foetal organism, it can be assessed via the foetal carotid findings. This, therefore is our contribution to the discussion on the indication for Caesarean section in cases of absent diastolic flow: Absence of diastolic flow in the umbilical artery and foetal aorta only without centralisation by increased perfusion in the foetal carotid, is, in our opinion, not an indication for Caesarean section. We believe, that foetal acidosis confirmed by foetal blood gas analysis indicated by the Doppler result, is an efficient completion of obstetrical management in risk pregnancies. Any further decision on conservative management or termination of pregnancy can be taken more easily on the basis of biochemical data, especially in situations, where conventional methods of foetal surveillance cannot clarify the perinatal risk sufficiently. PMID- 2202609 TI - Neurotensin is localized to paracrine cells in the urinary bladder of the turtle, Chrysemys picta. AB - Urinary bladder from the painted turtle, Chrysemys picta, contains a substantial population of endocrine/paracrine cells scattered through the mucosal epithelium which immunostains using antisera directed toward mammalian neurotensin (NT). Radiommunoassay of 0.1 N HCl extracts of Chrysemys bladder indicated an immunoreactive NT (iNT) concentration of 161 +/- 39 pmol/g tissue (n = 9), an amount lower but comparable in magnitude to that found in mucosal scrapings of the intestine (926 +/- 125 pmol/g, n = 9). Bladder and intestinal iNT were indistinguishable during chromatography on Sephadex G-25 and HPLC on mu-Bondapak C18 where they eluted at the same position as avian NT. Similar results were obtained by immunocytochemistry and radioimmunoassay of urinary bladders from Pseudemys scripta scripta, P. scripta elegans, and P. floridana, three emydid species closely related to C. picta, but not from Sternotherus odoratus and Trionyx spinifer asper, representatives of the families Kinosternidae and Trionychidae, respectively, although positive results were obtained with intestinal preparations from these species. NT cells were not seen in urinary bladder from Rana pipiens, Bufo marinus, Necturus maculosus, or Anolis carolinensis. Thus, the presence of NT-containing cells in urinary bladder is not common among subavian vertebrates and may even be restricted to the Emydidae family of chelonians. PMID- 2202610 TI - Degradation of gonadotropin-releasing hormones in the gilthead seabream, Sparus aurata. I. Cleavage of native salmon GnRH and mammalian LHRH in the pituitary. AB - The pattern and kinetics of degradation of native salmon gonadotropin-releasing hormone (sGnRH) and mammalian leuteinizing hormone-releasing hormone (LHRH) by pituitary bound enzymes were studied in the gilthead seabream, Sparus aurata. sGnRH and LHRH were incubated for different periods of time with membrane or cytosolic fractions of pituitary homogenates. At the end of the incubation, the degradation mixture was fractionated on reverse-phase high-pressure liquid chromatography. The degradation products were identified by comparing their retention times to those of synthesized GnRH fragments and by analyzing their amino acid composition. The main GnRH degradative activity resides in the cytosolic fraction of the pituitary homogenate. Both sGnRH and LHRH are rapidly degraded by pituitary cytosol, with 78.3 and 87.7% of the peptides, respectively, cleaved after 3 hr of incubation. Maximal degradation of sGnRH occurred at a pH range of 7 to 8. The main initial products of degradation of sGnRH and LHRH are the 1-5, 6-10, and 1-9 fragments. This suggests the involvement of two site specific peptidases, a Tyr5-Gly6 endopeptidase and a Pro9-Gly10NH2 peptidase or postproline cleaving enzyme. While the 1-6 and 1-9 fragments undergo rapid secondary degradation, the 1-5 is relatively stable. Competition experiments suggest that the endopeptidase cleaving the sGnRH at the Tyr5-Gly6 bond is not specific to the neuropeptide and is probably a general proteolitic enzyme. However, the cleavage at the 9-10 bond has a high degree of specificity to the Pro9-Gly10NH2 sequence found in sGnRH. The two proposed pituitary peptidases of S. aurata have some characteristics similar to those of rat hypophyseal and hypothalamic GnRH cleaving enzymes. No differences are found in hypophyseal GnRH degradative activity between females with occytes undergoing previtellogenesis or advanced stages of vitellogenesis. PMID- 2202611 TI - Degradation of gonadotropin-releasing hormones in the gilthead seabream, Sparus aurata. II. Cleavage of native salmon GnRH, mammalian LHRH, and their analogs in the pituitary, kidney, and liver. AB - The pattern and kinetics of degradation of native salmon gonadotropin-releasing hormone (sGnRH), mammalian luteinizing hormone-releasing hormone (LHRH), and some of their analogs by cytosolic enzymes of pituitary, kidney, and liver were studied in the gilthead seabream, Sparus aurata. The native peptides sGnRH and LHRH are rapidly degraded by all three tissues, LHRH being degraded faster than sGnRH. The kinetics of production of the peptide fragments suggest that initial cleavage of sGnRH and LHRH in the three studied tissues occurs at the 5-6 and 9 10 bonds. This indicates the initial activity of a Tyr5-Gly6 endopeptidase and a Pro9-Gly10NH2 peptidase or postproline cleaving enzyme. Secondary degradation of the main initial fragments (1-5, 6-10, and 1-9) is more intensive in the kidney than in the pituitary or liver. Substitution of the position 6 amino acid glycine by a dextrorotatory (D) amino acid such as in the D-Trp6-LHRH renders the 5-6 bond resistant to cleavage. However, whereas [D-Trp6]-LHRH is intensively cleaved at the Pro9-Gly10NH2 bond by the pituitary, its cleavage at this site by the kidney and liver is slow. This suggests a low activity of the Pro9-Gly10NH2 peptidase in the kidney and liver as compared to the pituitary. When, in addition to the position 6 substitution, the carboxy terminus Pro9-Gly10NH2 is modified to Pro9NET, such as in the [D-Ala6-Pro9NET]-LHRH and the [D-Arg6-Pro9NET]-sGnRH, the 9-10 cleavage site is also blocked, resulting in GnRH analogs highly resistant to degradation. The relationships between susceptibility of the different forms of GnRH to enzymatic degradation by the pituitary, kidney, and liver and their relative biological activities in S. aurata are discussed. We conclude that increased resistance of GnRH analogs to enzymatic degradation contributes to their superactivity. PMID- 2202612 TI - [Tuberculosis of the hand]. AB - Skeletal tuberculosis of the hand has become rare. The authors report a 27-year old female patient with tuberculous osteomyelitis of the middle phalanx of the left ring finger without occupational exposure of the hand and with positive chest roentgenogram. The case shows the diagnostic difficulties of the uncommon manifestation of skeletal tuberculosis in the short tubular bones of the hand. By means of a review of the literature the differential diagnosis, the course and necessary treatment are discussed. PMID- 2202613 TI - [Epithelioid hemangioma--a rare tumor of the hand]. AB - Epithelioid hemangioma is a rare disorder in Europe, affecting the skin and subcutaneous tissue in young adults. The presented cases all involve the hand, and, in one case, the intrinsic muscles and periosteum. PMID- 2202614 TI - Variability and adaptability in the genus Cebus. AB - Capuchins (Cebus) present an array of similarities to humans and apes in morphology, behavior and life history which raise a host of questions about the relations of these features to each other and about their evolutionary origins. As a genus and as individuals, capuchins possess marked adaptability and great variability in behavior. These two characteristics contribute directly to the biological success of capuchins. Variability and adaptability are also hallmarks of human behavior. PMID- 2202615 TI - Conceptual learning in capuchin monkeys. AB - This paper reviews concept learning in Cebus monkeys, focussing on their ability to use the identity relation, oddity and natural concepts. Capuchins are similar to other primate genera in their use of these concepts. The extant data on learning in primates generally reflect historical concerns with general processes of learning. An alternative approach which considers the tasks the animal faces in its natural environment may be better suited to the discovery of species unique characteristics of learning. This approach has not yet been applied to Cebus. PMID- 2202616 TI - Tool use in Cebus. AB - This paper summarizes early anecdotal information and systematic studies of tool use in capuchin monkeys (Cebus spp.). Tool use in capuchins is neither context specific nor stereotyped. The success of capuchins in using tools and in exploiting a variety of food resources in the wild derives from several factors: their manipulative abilities, interest in external objects and a tendency to explore the environment. In using tools, capuchins are similar to apes and more proficient than other monkey species. A cognitive approach indicates, however, that (in contrast with chimpanzees) they never develop an understanding of the requirements of the tool tasks presented. PMID- 2202618 TI - [Pathogenesis of corticoid-induced osteoporosis]. AB - Corticoid osteoporosis is the most important of the so-called secondary forms of osteoporosis. Although, in recent years, our knowledge of the pathomechanisms involved have been expanded, at the cellular and molecular-biological level, it remains incomplete. In practical-clinical terms, however, the following main effects of corticoids on bone metabolism and the calcium balance can be identified: inhibition of osteoblastic bone matrix synthesis and enhancement of osteoclastic bone absorption. This latter is promoted by inhibition of intestinal calcium absorption and tubular reabsorption of calcium with subsequent mild secondary hyperparathyroidism. These mechanisms suggest possibilities for the prevention and treatment of this form of osteoporosis. PMID- 2202617 TI - Social processes affecting the appearance of innovative behaviors in capuchin monkeys. AB - We consider the role of social factors in the appearance of innovative problem solving behaviors in capuchins. Processes supporting dissemination of innovative behaviors included social enhancement of interest in the objects and area around the task and (rarely) coaction. Factors inhibiting display of innovative behaviors included restricted access and requirements for social vigilance among animals of vulnerable social status and exploitation by noninnovators of others' behaviors. We urge caution in interpreting the increased appearance of novel behaviors in primates as evidence for imitation or facilitation and call for a more rigorous experimental investigation of social learning in primates. PMID- 2202619 TI - [Efficacy of a bismuth combination preparation. Efficacy in the treatment of chronic active gastritis and non-ulcerous dyspepsia]. AB - In an open, randomized controlled study, the effect of a combined bismuth preparation, bismuth nitrate and bismuth aluminate on the elimination of Helicobacter pylori, inflammatory activity in the gastric mucosa in chronic type B gastritis, and on the patient's symptoms was investigated. Included in the study were 36 patients with non-ulcerous dyspepsia and chronic gastritis. Twelve patients (Group A) received 4 x 1 tablet a day (800 mg total daily dose), 12 patients (Group B) 2 x 2 tablets a day (800 mg total daily dose), 12 patients (Group C) 2 x 1 tablet (400 mg total daily dose) for a period of 4 weeks. Elimination of Helicobacter pylori was observed in 73% of the patients in Group A, in 87% in Group B, but in only 16% in Group C. Inflammatory activity, measured in terms of polymorphonuclear cell infiltration, regressed noticeably in Group A und B (p less than 0.01), but not in Group C. In all patient groups symptoms regressed significantly (p less than 0.01). Bismuth and methemoglobin concentrations in the serum were within the normal range in all patients on conclusion of treatment. PMID- 2202621 TI - [Hyperinsulinemia. Current thinking on cardiovascular risks]. PMID- 2202620 TI - [Cochlear implant--possibilities and limitations]. AB - Provided that the auditory nerve is fully preserved and that the hearing impairment has not persisted for more than a few years, the cochlear implant offers a satisfactory, though not perfect, replacement for the defunct inner ear. Unfortunately, prior to operation, the residual function of the auditory nerve in patients with labyrinthine deafness cannot be determined quantitatively, but can merely be noted to be present or not. As the duration of the impairment lengthens, we must expect progressive degeneration of auditory nerve fibers, and increasing deprivation of the central auditory pathways. The limitations of cochlear implants are thus determined by an impairment that has persisted for decades, as also early-prelingual-development of the impairment. This also means that adults who were born deaf should not be recommended for the procedure. This should stimulate us all the more to create the conditions to ensure that the young deaf child can benefit from cochlear implantation at as early an age as possible. At the present time, we are attempting to work out surgical techniques and rehabilitative measures for cochlear implants in young deaf children. PMID- 2202622 TI - [Diagnostic value of cerebrospinal fluid study in multiple sclerosis]. AB - Multiple sclerosis ist a very frequent chronic inflammatory disease of the central nervous system. Since clinical and neuro-imaging findings often may be ambiguous, cerebrospinal fluid examination has received great importance for diagnosis. By that method it becomes possible to differentiate inflammatory from noninflammatory diseases. Furthermore, cerebrospinal fluid findings are discussed which seem to be characteristic for multiple sclerosis. PMID- 2202623 TI - Significance of the Randle-Mechanism in the etiology of diabetes type II. AB - In 1963, Randle, Garland, Hales and Newsholme proposed the existence of a glucose fatty-acid cycle in which excess lipid oxidation leads to inhibition of glucose oxidation in muscle tissue. Calorimetric studies confirmed these observations in man. However, as the rate of glucose oxidation is limited in the resting state, a defect in glucose oxidation can only have limited effects on glucose tolerance. The demonstration, by our group, of inhibition of glucose storage following increased lipid oxidation has suggested that excess lipids might induce glucose intolerance through an inhibitory effect on glucose storage. This might be explained by a decrease in glycogen mobilization (a factor that regulates glucose storage) as a consequence of the inhibition of glucose oxidation by excess fatty acids, according to Randle. In obesity, the resistance to glucose storage is present as a constant phenomenon. It is overcome by adaptation of the glycemic response to carbohydrate ingestion. This rise in glycemia, appearing as impaired glucose tolerance, allows glucose to be stored in spite of the resistance to glucose storage. But, simultaneously, this rise in glycemia decreases the possibility for glycogen mobilization, thus further limiting glucose storage. With the duration of obesity and the persistence of the hyperlipacidemia, when the glycemic response to a meal does not return any more to basal levels, the capacity for glucose storage becomes markedly impaired, so that glucose intolerance reaches the stage of diabetes. In type II diabetes of the obese, decrease in insulin response appears a late phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2202624 TI - Hyperinsulinemia and its sequelae. AB - It is now well recognized that insulin resistance and/or hyperinsulinemia are characteristic of a number of common human disease states including obesity, non insulin dependent diabetes mellitus (NIDDM), essential hypertension, and atherosclerotic cardiovascular disease. More recent evidence suggests that impaired insulin action and elevated levels of circulating insulin may also be present in a substantial proportion of apparently healthy nonobese individuals. Considerable attention is now being focused on the potential long term adverse consequences of elevated circulating insulin levels. In particular, the frequent concurrence of these clinical disorders of carbohydrate metabolism, lipid metabolism, and vascular disease has led to the hypothesis that insulin resistance and the ensuing hyperinsulinemia may be a common pathophysiologic factor in the etiology of these disease states. In this review, we will examine the evidence for this hypothesis with particular attention to the adverse effects of chronic hyperinsulinemia. PMID- 2202625 TI - Essential hypertension--a metabolic disorder? PMID- 2202626 TI - Effects of diuretics on insulin secretion and glucose disposal. PMID- 2202628 TI - Long-term effects of beta-blockers and Ca2+(+)-antagonists on glucose metabolism. PMID- 2202629 TI - Effects of ACE-inhibitors in hypertensive and normotensive diabetic patients with diabetic nephropathie. AB - Diabetic nephropathy leading to end stage renal failure with 30 to 40% cumulative incidence remains one of the great life threatening dangers for type I diabetics. Its natural history gets its impact due to the biochemical sequela of diabetic hyperglycemia such as polyol accumulation or glycation processes. Functional changes may be detected by microalbuminuria which in turn is followed by intraglomerular, intrarenal and finally systemic hypertension. Hypertension itself seems to be part of the self perpetuating process, and therefore antihypertensive treatment has been shown to be an effective area. Antihypertensive treatment by itself is effective in the slowing down of the decline of glomerular filtration rate, together with decreasing the amount of albumin excretion and, therefore, might be expected to be of value in prolonging the renal prognosis over a length of time. From the theoretical point of view the ACE inhibitors were looked upon as beneficial and therefore preferable as interventional tools because of their special effects of blood pressure redistribution within the glomeruli. Long term reports and a lot of short and intermediate term controlled studies were able to confirm the expected effects. Whether this is the case also in borderline hypertension or even in normotensive diabetics remains finally to be established. The question of long term effects such as survival rates and the superiority of antihypertensive treatments with beta blockers or drug combinations, or whether these results reflect merely their systemic blood pressure lowering effects remain finally to be elucidated. PMID- 2202627 TI - Glucose metabolism and calcium antagonists. AB - High blood pressure, but also diabetes mellitus and even glucose intolerance are well known risk factors for premature cardiovascular morbidity and mortality. To counteract these sequelae, it is obvious that drug treatment of hypertension should not adversely affect the glucose homeostasis in nondiabetic as well as in diabetic patients. Therefore, the findings that calcium antagonists could dose dependently throttle the insulin output after addition of glucose in pancreas perfusion experiments in vitro were of considerable concern. Within the last years, most of more than 100 short-term and long-term trials in diabetic and non diabetic patients were able to show that different calcium antagonists at their "usual" antihypertensive dosages did not impair the glucose metabolism, whereas results of acute studies, especially with higher doses and after a glucose challenge, were more controversial. However, in all of the 13 long-term follow-up trials (up to 5 years) with determinations of the glycated hemoglobin published to date, this most relevant parameter remained unchanged. Thus, currently available data indicate that calcium antagonists do not alter glucose handling at a clinically relevant degree, both in non-diabetic or diabetic patients, so that it is not justified to withhold the benefits of these medications from hypertensives out of fear to introduce a deterioration in their carbohydrate homeostasis. PMID- 2202630 TI - Effects of ACE-inhibition on glucose metabolism. AB - ACE inhibition is widely used for treatment of arterial hypertension or congestive heart failure. No change occurs in glucose metabolism either in diabetic or non diabetic subjects. No change occurs in glucose metabolism in patients with chronic renal failure. Glucose intolerance induced by diuretics is attenuated when ACE inhibitor is associated with thiazides. In some very rare circumstances (with high plasmatic levels of norepinephrine), insulin sensitivity seems to be enhanced by captopril. Then, in clinical use, no adverse effect occurs with ACE inhibition in non diabetic or diabetic subjects. Under thiazide treatment, ACE inhibitors protect against glucose intolerance. PMID- 2202631 TI - Clinical studies with CE-inhibitors in diabetes. AB - Early antihypertensive intervention in diabetes often means intervention in a cluster of cardiovascular risk factors including glucose intolerance per se, hyperlipidemia, obesity and hypertension, which are not just coexistent but may be causally linked together by the resistance of peripheral tissues to the action of insulin. Blood pressure lowering treatment should therefore be metabolically neutral in order to avoid aggravation of this risk factor syndrome. Clinical studies applying CE-inhibitors in type II diabetes are critically reviewed under this aspect. The majority of the available studies in type II diabetes report a reduction of insulin resistance and a marginal improvement of metabolic control. The order of magnitude in HbA1 reduction is nearly 10% of the glycosylated haemoglobin, reduction of fasting and postprandial blood glucose approximates 1 mmol/l. From a more extended view, considering essential hypertension as insulin resistant and thus possibly "prediabetic" state, this marginal metabolic effect gets further support from recent studies in essential hypertension consistently reporting an improvement of metabolic parameters of similar magnitude. This might become a central argument in the discussion about individualized and metabolically neutral antihypertensive treatment in essential hypertension. PMID- 2202632 TI - Longterm effects of captopril and hydrochlorothiazide on glucose metabolism in the hypertensive patient. PMID- 2202633 TI - Effects of kinins on glucose metabolism in vivo. AB - Current concepts of the physiological importance of the kinin/prostaglandin system view these tissue factors as part of a defense system, which protects tissues from potentially noxious factors, such as hypoxia or destructive inflammatory reactions. This kinin-triggered defense reaction includes an improvement in cellular energy metabolism. The latter is brought about in peripheral tissues by an increased availability of glucose for anaerobic and aerobic glycolysis, whereas in liver tissue, energy-consuming reactions such as gluconeogenesis are attenuated. There is evidence that such favorable effects can also be produced in man when kinins are administered systemically. Prostaglandins are most likely the second messengers of kinin-induced metabolic effects. Thus, it may be advantageous to increase the availability of kinins either by exogenous infusion or by inhibiting endogenous degradation during postoperative stress or in diseases such as diabetes mellitus, in which glucose metabolism is severely disturbed. PMID- 2202634 TI - Epidemiology and risk factors of macrovascular disease in diabetes mellitus. AB - Cardiovascular diseases are the major cause of morbidity and mortality in the diabetic patient. The acceleration of atherogenesis occurs in all types of diabetes and culminates in such fatal complications as myocardial infarction, stroke and gangrene. Subjects with non-insulin-dependent diabetes mellitus exhibit a 3-4 times higher rate of cardiovascular mortality than non-diabetic persons. Since it was not possible to explain the excess risk by the traditional cardiovascular risk factors, various hypothesis have been put forward. These include certain aspects of blood pressure elevation, lipid changes, hyperinsulinemia, abnormal hemostasis, and impaired kidney function. PMID- 2202635 TI - Immunohistochemistry of the hepatic extracellular matrix in acute viral hepatitis. AB - The distribution of several extracellular matrix components in the liver of patients with acute viral hepatitis was studied by light and electron microscopy using indirect immunoperoxidase methods. Light microscopy revealed type III and type V collagen and fibronectin in the portal tracts and the area of focal necrosis, showing cell infiltration. Type III and type V collagen were more strongly stained in the periphery of focal necrosis. Type IV collagen was seen around the vessels and hepatocytes near the focal necrosis. Electron microscopy showed many transitional Ito cells in the area of focal necrosis and fibroblasts were observed in the portal tracts, showing collagen fiber deposition. Numerous collagen fibrils were observed around fibroblasts, Ito cells and hepatocytes. Using immunoelectron microscopy, type III and type IV collagen and fibronectin were observed in the rough endoplasmic reticulum of Ito cells and hepatocytes localized near the area of focal necrosis or fiber deposition. In addition, type IV collagen was seen in the rough endoplasmic reticulum of endothelial cells forming capillary vessels. These results suggest that several extracellular matrix components such as types III, IV and V collagen and fibronectin, produced by Ito cells, hepatocytes or endothelial cells, play important roles in the healing of liver damage in acute viral hepatitis. PMID- 2202636 TI - Isolated perfused cirrhotic human liver obtained from liver transplant patients: a feasibility study. AB - Cirrhotic livers obtained from eight patients who underwent orthotopic liver transplantation were perfused through the portal vein and hepatic artery in a closed recycling system for periods ranging from 2 to 7 hr. An average perfusion flow of 451 ml/min was used, with about 80% coming from the portal vein and 20% from the hepatic artery. The livers appeared to remain viable as assessed by gross appearance, stable portal vein and hepatic artery pressures, oxygen consumption and bile production. The extraction ratio of indocyanine green by the perfused livers averaged 0.098 (range = 0.023 to 0.168); that of propranolol averaged 0.445 (range = 0.126 to 0.813). Using the multiple-indicator dilution curve method, shunts greater than 15 microns in diameter were demonstrated between the portal and hepatic veins in six of eight cases, whereas shunts from the hepatic artery to the hepatic veins were absent. Perfusion of human livers obtained during hepatic transplantation is a fairly simple procedure that will allow researchers to gain new insights into cirrhosis in humans. PMID- 2202639 TI - Significance of extrahepatic replication of hepatitis B virus. PMID- 2202638 TI - Autoimmunity and liver disease. PMID- 2202637 TI - Analysis of hepatic T lymphocyte and immunoglobulin deposits in patients with primary biliary cirrhosis. AB - The histological findings in patients with primary biliary cirrhosis have been well-defined and are often used in the clinical staging of disease. However, it has only been with the development of reagents that phenotypically characterize the lymphoid infiltrate that attempts have been made to correlate pathophysiology with immune effector populations. Indeed, the inflammatory hepatic lesions in primary biliary cirrhosis have been described as containing CD4-positive and CD8 positive T cells. Less clear, however, have been the T cell receptors in these lesions. Further, the data on immunoglobulin deposits in hepatic lesions have been less well-defined; this deficit may be a result of the quality of polyspecific sera and difficulties in background. To address these issues, we have used a battery of well-defined monospecific and polyspecific reagents to phenotypically define the occurrence of lymphoid cells in the livers of patients undergoing transplantation. Furthermore, we have defined these same markers on T cell lines derived from liver, regional lymph node and peripheral blood. The predominant cell type in the mononuclear infiltrate is the CD3+, CD4+ T lymphocyte bearing the T cell receptor alpha beta. T cell lines from the same patients demonstrate similar findings. Of special importance, however, was the detection of CD20+ B cells and Ig+ cells in the lymphoid infiltrate. Indeed, we also readily demonstrated the presence of immunoglobulin on the surface of biliary epithelium. These data suggest that mechanisms involved in the pathophysiology of primary biliary cirrhosis may include both T cell and antibody mechanisms. The results also underscore the need to develop a functional, and not just a phenotypical, assay of the inflammatory infiltrate. PMID- 2202640 TI - The streaming liver: can the age of a hepatocyte be determined from its position on the portohepatic radius? PMID- 2202641 TI - Diagnosis and onset of acute hepatitis delta virus infection. PMID- 2202642 TI - Medicaid could bust state budgets in the '90s. PMID- 2202643 TI - McCarthy assesses the issues, looks to future strategy debate. AB - Facts aren't always enough to engender change, but they have helped the AHA make progress in influencing health care policy decisions, according to AHA president Carol McCarthy, PhD. In a speech presented at the AHA's 1990 annual convention in Washington, DC, McCarthy takes stock of the past year's events and how they might affect hospitals. PMID- 2202644 TI - Blue Cross exec envisions tighter linkages with hospitals. PMID- 2202645 TI - CEO's service orientation earns top Texas business award. PMID- 2202646 TI - ACOG president leads fight against infant mortality. PMID- 2202647 TI - Volunteer directors are polishing their professional image. PMID- 2202648 TI - 3M: diversity and strategic planning are key. PMID- 2202649 TI - Execs plan, make decisions with help of EIS (executive information systems). PMID- 2202650 TI - [Effect of high carbohydrate and high fat diets on plasma glucose, insulin and lipids in normal and hypertriglyceridemic subjects]. AB - The fasting plasma glucose, insulin and lipids response to high-carbohydrate-low fat diets and low-carbohydrate-high-fat diets in normal subjects and patients with endogenous hypertriglyceridemia was observed. The normal, high carbohydrate and high fat diets consisted of 60%, 80% and 40% carbohydrate, 25%, 5% and 45% fat and 15% protein of total calorie respectively. The fasting plasma glucose levels increased (P less than 0.01) on day 1, insulin increased on day 3 (P less than 0.01 and P less than 0.05) and TG levels increased on days 3 and 5 after taking high carbohydrate diets both in the normal and hypertriglyceridemic groups. The fasting plasma TC and HDL-C decreased on high carbohydrate diets mainly in the hypertriglyceridemic group. The fasting plasma glucose slightly decreased on day 5, TG decreased on day 1 (P less than 0.05) and TC increased on day 1 and 3 (P less than 0.01) after taking high fat diets, but no differences were observed in insulin levels. Fasting plasma HDL-C levels in the normal group remained unchanged, but significantly decreased 3 days after taking high fat diets in the hypertriglyceridemic group (P less than 0.001). Our results indicate that high carbohydrate intake may be an important cause of hypertriglyceridemia in our country. This diet may cause a slight increase in the blood glucose level, which in turn stimulates an increase in plasma lipids and decrease in HDL-C, which is associated with an increase in the incident of coronary heart disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2202651 TI - [States of dentine surface and interface between dentine and coupling agent]. AB - In order to research the states of dentine surface and dentine surface primed with coupling agent, we used microscope, transmission electron microscope (TEM) and solid fluorescence method. Observed under microscope, patterning of dentinal tubules and their poles was very explicit; through the view of interface between coupling agent adsorbed and human dentine powder by TEM, it was revealed that the coupling agent was adsorbed onto the dentine surface as if it "grew out" of the dentine surface; through examination of interface between the coupling agent adsorbed and dentine surface by fluorescence spectrum, which differed from that of the coupling agent or dentine surface, i.e., this fluorescence spectrum of interface changed obviously (red shift). This phenomenon indicated that there was a chemical reaction occurring between tooth surface and adsorbed coupling agent. Therefore we can conclude that the three examinations are necessary to provide the argument for establishment of chemical bonding mechanism between dentine and coupling agent. PMID- 2202652 TI - [The changes of beta-glucuronidase in rabbit model with calcium bilirubinate stone]. AB - The aim of the present study is to determine the beta-glucuronidase changes in bile and hepatobiliary tissue of rabbit model having pigment gallstone by means of biochemical and enzymehistochemical assay methods. The result showed both of the bacterial and non-bacterial beta-glucuronidase take part in the course of pigment gallstone formation. The bacterial beta-glucuronidase level increased quickly before the formation of gallstone, then decreased with control of bacterial infection. Non-bacterial beta-glucuronidase increased slowly in pro formation stage of gallstone, then kept high level for long period of time. The relationship between beta-glucuronidase and pigment gallstone formation is also discussed. PMID- 2202653 TI - [An epidemiological survey of gallstones with gray-scale ultrasound]. AB - Gray-scale real-time ultrasound has been employed to investigate gallstone with a positive result of 553 cases out of 15,856 healthy subjects in city and countryside, the incidence being 34.88%. The feature of incidence is as follows: 1. The incidence of the simple gallbladder stone is more common than that of the other sites (male is about 81.15%, female is about 87.29%); 2. The incidence of gallstones of city residents is higher than that of the country people with significant difference statistically (P less than 0.01); 3. The incidence of gallstone in female city residents is higher than male, about 2.5:1, which shows significant difference. (P less than 0.01); 4. The incidence of gallstones in female city residents is higher than in countryside (P less than 0.01); 5. There is no significant difference in the incidence of gallstone between male and female in the countryside (P greater than 0.05); 6. There is no significant difference in the incidence of gallstones between city male and the male in the countryside (P greater than 0.05); 7. Either in the city or in the countryside, it has been shown that there is a tendency of increasing incidence of gallstone with age in both sexes (P less than 0.01). The relationship between the gallstone and the clinical symptoms has been discussed in this paper. PMID- 2202655 TI - Topical idoxuridine for treatment of genital warts in males. A double-blind comparative study of 0.25% and 0.5% cream. AB - Fifty heterosexual male patients with histologically verified genital warts of short duration (less than 3 months) were randomly allocated to treatment with either 0.25% or 0.5% idoxuridine cream. The application of the cream to the warts was performed twice daily for an initial period of 14 days, whereafter patients with partial improvement or no response were retreated in the same way for another period of 14 days. Patients not completely healed after 28 days were regarded as treatment failures and withdrawn from the study. After the initial treatment period of 14 days, 19 of 25 patients (76%) treated with 0.5% idoxuridine cream, and 9 of 25 patients (36%) treated with 0.25% idoxuridine cream were completely healed. This difference is significant (p less than 0.01). The corresponding figures at the second follow-up examination (28 days after start of the study) were 19 of 25 (76%) and 13 of 25 (52%), respectively. At the last follow-up examination three months after start of treatment, four patients treated with 0.5% idoxuridine cream and five patients treated with 0.25% idoxuridine cream had a relapse. Thus, the overall rate of complete healing was 15 of 25 (60%) for the patients treated with 0.5% idoxuridine cream and 8 of 25 (32%) for those treated with 0.25% idoxuridine cream. The difference is significant (p less than 0.01). No adverse reactions were observed or reported by the patients. PMID- 2202654 TI - Sexually transmitted diseases in Africa. PMID- 2202656 TI - A comparison of cytobrush and cotton swab sampling for the detection of Chlamydia trachomatis by cell culture. AB - A cytobrush was compared with a cotton-tipped aluminium shafted swab for the collection of 2024 paired endocervical specimens for the culture of Chlamydia trachomatis. There was no significant advantage with the use of either device with respect to the number of positive specimens detected or the number of inclusions present in positive specimens. However, the use of cytobrushes resulted in an increased level of cervical bleeding and increased collection of cervical mucus resulting in difficulties in the handling of laboratory specimens. PMID- 2202657 TI - Desquamative inflammatory vaginitis. A review. AB - Desquamative inflammatory vaginitis is an uncommon cause of an intractable vaginitis often accompanied by serious dyspareunia, which can occur at any stage of reproductive life and after the menopause. The cytological changes are identical with those seen in atrophic vaginitis yet the disorder often occurs in the presence of apparently normal ovarian function. Vaginal synechiae and stenosis develop in an appreciable number of patients. Treatment is unsatisfactory though there is some response to either local or systemic steroid therapy. The literature is reviewed and the association of some cases with lichen planus of the mouth and genitals discussed. Its causation and natural history remain largely unknown and there is as yet, insufficient evidence to regard it as a single entity. It is likely that the incidence of the disorder is underestimated. PMID- 2202658 TI - Syphilis in art: an entertainment in four parts. Part 4. PMID- 2202659 TI - The protecton: the unit of humoral immunity selected by evolution. PMID- 2202660 TI - The protection: a view from the bunker. PMID- 2202662 TI - Commentary on "The protection: the evolutionarily selected unit of humoral immunity". PMID- 2202661 TI - A critique of the Cohn-Langman protection theory. PMID- 2202663 TI - Diversity 1990. PMID- 2202664 TI - A comment on allelic exclusion, 'D-disaster' and germ-line gene specificities. PMID- 2202665 TI - The published data. PMID- 2202666 TI - The role of imprint cytology in diagnosis of various bone and joint diseases. AB - Using imprint cytodiagnosis on 63 cases of bone and joint lesions, there was only one false negative result, with ten unsatisfactory smear preparations giving an overall accuracy of 82.25 per cent. Imprint cytodiagnosis is simple, cheap, rapid easy to perform and interpret because of its better cytomorphological evaluation. The accuracy rate is high when used in conjunction with various cytochemical stains. PMID- 2202667 TI - Carcinoma bladder: comparative evaluation of urinary cytology, excretory urography and ultrasonography. AB - A total of 63 patients with 85 bladder tumors were evaluated with excretory urography (IVU), ultrasonography and urine cytology, before being subjected to cystosocopy and biopsy. An attempt was made to evaluate accuracy of detection by different modalities, individually and combined together. Untrasonography and IVU detected 90 percent and 75 percent of tumors respectively while cytology was positive in 63 percent patients. Ultrasonography was superior to IVU, and, Urinary cytology, despite its low catch, could detect few cases where both the previous mentioned modalities had failed. Larger tumors situated on posterior and lateral walls were consistently detected by ultrasonography. Tumor staging by ultrasonography correlated well with final staging in infiltrating tumors. Thus it is concluded that the two non-invasive procedures, sonography and urine cytology must be routinely used for evaluation of fresh cases and in follow up of bladder tumors. PMID- 2202668 TI - Clinical evaluation of angulated abutments for the Branemark system: a pilot study. AB - Where fixture placement and inclination had not been optimal from a restorative perspective, angulated abutments were used to overcome compromised esthetic and functional results in situations of complicated anatomy. The angulated abutment is a treatment adjunct that provides flexibility for ensuring successful treatment when a variety of reconstruction problems are confronted. PMID- 2202669 TI - The surface characteristics produced by various oral hygiene instruments and materials on titanium implant abutments. AB - The purpose of this investigation was to determine the comparative surface roughness produced by various oral hygiene instruments and materials on titanium implant abutments. Ten Branemark titanium abutment cylinders were used, with one serving as an untreated control. One abutment was used to evaluate each of nine oral hygiene instrumentation methods used for specified lengths of time or instrument strokes. Each abutment was sonically cleaned, air dried, and viewed with a scanning electron microscope. Polaroid photomicrographs were made of abutment surfaces at predetermined magnifications. They were analyzed by three investigators, who compared individual test parameters in terms of time application or stroke number. The resulting abutment surface roughness was also evaluated. The rubber cup with flour of pumice created a smoother surface than the control; the interdental brush, soft nylon toothbrush, plastic scaler, Eva plastic tip, rubber cup, and Cavi-jet left a surface comparable to the control; the metal scalers and the Cavitron created a severely roughened surface. PMID- 2202670 TI - Clinical report on the success of 47 consecutively placed Core-Vent implants followed from 3 months to 4 years. AB - This report presents the clinical outcome of 47 consecutively placed Core-Vent implants inserted in 35 patients followed for 2 to 4 years by clinical and 3 to 48 months by radiographic examination. The implants were used in mandibles and maxillae to support single crowns, overdentures, and fixed prostheses splinted to natural teeth as recommended by the manufacturer. Of the 47 implants, 43 could be examined. A total of 11 implants was removed, nine because of progressive vertical bone loss and two because of fractures. The vertical bone loss was calculated for the 32 remaining implants. Twenty-eight implants demonstrated a bone loss of more than 2 mm and 16 showed a loss of more than one-third of the implant height. According to the criteria proposed by Schnitman and Shulman in 1979, the total success rate was 37.2%. When using the criteria suggested by Albrektsson et al in 1986, the total success rate was calculated to be 9.3%. PMID- 2202672 TI - Tissue reaction involving an intraoral skin graft and CP titanium abutments: a clinical report. AB - Focal areas of gingival hyperplasia surrounding the transmucosal portions of titanium implants have been attributed to poor hygiene, lack of attached gingival tissues, and titanium allergy. Following mandibular vestibuloplasty and placement of a split-thickness skin graft, two of five patients developed persistent proliferation of the epithelial tissue surrounding endosseous CP titanium dental implants. In both circumstances, traditional gingivectomy procedures, chemotherapeutic agents, and aggressive oral hygiene measures failed to adequately control the hyperplastic response. Following replacement of the titanium abutments with custom-fabricated gold abutments, the epithelial condition appeared to return to normal. PMID- 2202671 TI - Psychological impact of osseointegrated dental implants. AB - This longitudinal study of 39 patients who underwent treatment involving osseointegrated implants examined problems in oral and psychosocial functioning, expectations and experiences of difficulties with surgery, satisfaction with surgery, body image, neuroticism, self-concept, and extroversion. Patients completed six questionnaires from before phase 1 surgery to the final recall appointment for the new prosthesis (12 to 18 months after phase 1 surgery). The most common problems reported before treatment were those associated with eating; esthetics was less of a concern. Significant improvements in all problem areas were observed immediately after phase 2 surgery. Expectations of surgery-related problems were generally consistent with experiences immediately after phase 1 surgery, but more negative than experiences following phase 2 surgery. Body image before treatment was most negative vis-a-vis teeth. Significant improvements were found not only regarding teeth, but also on facial, mouth, and even overall body image. Satisfaction scores were generally high, but showed continued improvements through the final assessment. The only group experiencing negative outcomes consisted of patients scoring high on neuroticism. PMID- 2202673 TI - Some recent advances in neuro-oncology with particular reference to newer techniques for diagnosis and prognostication. PMID- 2202675 TI - [Analysis of parallelometer for models in removable partial dentures]. PMID- 2202674 TI - [Mixed impression for complete dentures in an irradiated patient]. PMID- 2202676 TI - [Multicenter study of the anti-inflammatory and analgesic effects of niflumic acid with antibiotics, used preoperatively in dentistry]. PMID- 2202677 TI - [Use of composites in the scope of pre-prosthetic treatment]. PMID- 2202678 TI - [Enamel and dentin adaptation of a new adhesive system from the Pierre Rolland Laboratory]. PMID- 2202679 TI - [Was there implantology 7000 years ago?]. PMID- 2202680 TI - [From animal structures to reflective thought]. PMID- 2202681 TI - [Primate evolutionary modalities and modern man, with particular reference to dental characteristics]. PMID- 2202682 TI - [Teeth from monkeys to Mozart]. PMID- 2202683 TI - [Precision and homogeneity of metal castings]. PMID- 2202684 TI - Endocrine disturbances and reduced sympathetic activity in the development of obesity. AB - Obesity is associated with a number of changes in the endocrine system. Some of them occur as a result of the obesity, and some, such as changes in the secretion of adrenal steroids, may be causal. The importance of a reduction in the activity of the sympathetic nervous system in the control of obesity and nutrient regulation has been discussed. The influence of insulin and adrenal steroids on this system have been discussed in relation to changes in the activity of the sympathetic nervous system. PMID- 2202685 TI - [Preoperative autologous blood donation]. AB - There are three basic forms of the 170-year-old autologous blood transfusion. The intraoperative and perioperative autologous blood transfusion and the preoperative autologous blood donation and retransfusion. The latter is a preferred task of blood transfusion services. Indications and contraindications have to be carefully considered. Each step from the decision for autologous donation to the retransfusion has to be carried out with the same conscientiousness as any other preparation of blood units and performance of hemotherapy. Although the interest in autologous blood deposit has increased in the last 5 years the percentage of autologous blood donation is very small. In order to include all suitable patients in an autologous predeposit programme a close and understanding cooperation between hospitals and transfusion services is necessary. The frequency of autologous blood donations decreases if these requirements are not complied with. PMID- 2202686 TI - Microbiological evaluation of clindamycin as a root canal dressing in teeth with apical periodontitis. AB - The present investigation was designed to study the effect of clindamycin on root canal infection when placed as an intracanal dressing. Twenty-five teeth with necrotic pulps and periapical radiolucencies were included. Following initial bacteriological sampling and routine instrumentation, clindamycin powder mixed to a paste with saline was applied for 14 days. The presence or absence of bacteria was determined in samples taken immediately after removal of the dressing, and after a period of 7 days during which the canals were filled with sampling fluid. Bacteria were recovered from four and six teeth respectively. The results indicated that clindamycin offered no advantage over conventional root canal dressings, such as calcium hydroxide, and it is therefore not recommended for use in routine endodontic therapy. PMID- 2202687 TI - The assessment of pulpal vitality. AB - This is a review of methods of assessing dental pulp vitality in order to assist the clinician in diagnosis and treatment planning. It covers the patient's history, clinical examination, assessment of radiographs, thermal tests, electrical tests, test cavities, use of anaesthesia, and the recent application of laser Doppler flowmetry. PMID- 2202688 TI - In vivo effects of cyclosporin A on murine B-cells responding to type III pneumococcal polysaccharide. AB - The effect of cyclosporin A (CSA) on the antibody response to pneumococcal polysaccharide type III (a T-independent class 2 antigen) was investigated in mice. A single oral CSA administration (50 mg/kg) was able to depress (40%) the primary antibody response evaluated as spleen plaque-forming cells. Repeated treatments (12-50 mg/kg x 5) resulted in a higher degree of inhibition (80%) of anti-SIII response. Both single and repeated CSA treatments were active only when administered concomitantly with or after immunization, whereas no effects were seen with drug pretreatment. Comparable inhibitions of anti-SIII response were observed in control and nude mice suggesting a direct effect of CSA on B-cells. PMID- 2202689 TI - Effects of artemisinin, dihydroartemisinin and arteether on immune responses of normal mice. AB - Artemisinin (Qinghaosu) is a potent antimalarial sesquiterpene lactone isolated from the Chinese herb Artemisia annua. Arteether, a potent semisynthetic analogue of dihydroartemisinin is being developed by the World Health Organization as the artemisinin derivative of choice for the treatment of malaria. All three agents in doses of 400 and 600 mg/kg body weight were found to exhibit marked suppression of humoral responses, as measured by the hemolytic plaque assay, with arteether being the most potent. These agents did not alter the delayed-type hypersensitivity response to sheep erythrocytes at the same dose levels. In addition, all three agents were found not to possess any anti-inflammatory activity when tested on carrageenan-induced oedema. These results indicated that these agents have a selective immunosuppressive activity. They did not exhibit immunostimulating activity in contrast to what has been reported for sodium artesunate. PMID- 2202690 TI - Hydrolysis and binding of leucine enkephalin to lymphomic and erythroleukaemic cell lines. AB - Hydrolysis and binding of labelled leucine enkephalin have been measured in the presence of cell lines of lymphoid and erythroid origin. The radioactive label was found to be associated to all lines studied. In the presence of these cells, enkephalin is rapidly hydrolyzed, forming three tyrosine-containing peptides: Tyr, Tyr-Gly and Tyr-Gly-Gly. Conversely, the presence of selective protease inhibitors reduces both enkephalin degradation and binding. Data obtained suggest the involvement in enkephalin hydrolysis of aminopeptidases, dypeptidylaminopeptidases and dypeptidylcarboxypeptidases. In addition, they suggest that the radioactive label associated to cells can be related to the peptides formed by the enzyme degradation of enkephalin and not to the intact pentapeptide. PMID- 2202692 TI - Robert D. Pugatch. Sixth distinguished scientist, Armed Forces Institute of Pathology. PMID- 2202691 TI - Interleukin-6 gene expression and production induced in human monocytes by membrane proteoglycans from Klebsiella pneumoniae. AB - The present study was designed to investigate the effect of membrane proteoglycans (MPG) from Klebsiella pneumoniae on IL-6 production by human peripheral blood monocytes. Exposure in vitro to MPG induced release of IL-6 activity from human monocytes, as assessed by the 7TD1 hybridoma assay. MPG induced hybridoma growth factor activity was blocked by anti-IL-6 antibodies. MPG induced expression in human monocytes of IL-6 mRNA transcripts as assessed by Northern blot analysis. Induction of IL-6 in mononuclear phagocytes may play a role in the immunomodulatory activity of MPG. PMID- 2202693 TI - Pitfalls in the diagnosis of metastatic disease or local tumor extension with modern imaging techniques. PMID- 2202694 TI - Hyperthermia in cancer treatment. AB - Hyperthermia, used as an adjunct to radiation therapy, can increase tumor regression significantly. When used as a local (as opposed to regional or systemic) modality, proper treatment requires detailed knowledge of tumor and normal tissue geometry, and physiologic parameters such as perfusion and thermal conductivity. A brief review of local heating techniques and details of two techniques used to treat brain tumors are provided: Scan Focused Ultrasound and Interstitial Ferromagnetic Seed Implants. These techniques require the most sophisticated use of diagnostic radiology methods. Data from several modalities such as CT, MRI, angiography, and xenon CT perfusion studies must be merged into a consistent data set. This data set must be indexed precisely relative to the treatment apparatus. Real-time noninvasive temperature monitoring of the treatment field has not been achieved at this time, but is of interest to researchers in hyperthermia. PMID- 2202695 TI - Advances in cardiac imaging modalities. Fast computed tomography, magnetic resonance imaging, and positron emission tomography. PMID- 2202696 TI - One-month-old infant with increasing head size. PMID- 2202697 TI - Cytological screening history of patients with early invasive cervical cancer. AB - The value of population screening for cervical cancer has recently been questioned. The purpose of this study was to examine the cytological screening history in 100 consecutive patients undergoing Wertheim's hysterectomy for early invasive cervical cancer. Twenty three per cent of the patients were never screened; the screening history was unavailable in 11%; the patient was referred appropriately in 21%; there was a delay in referral for gynaecological assessment in 21%; the patient's previous cervical smear before referral was normal in 24%. If population screening in Ireland is to have an impact on mortality from cervical cancer, the results of this study indicate that greater attention needs to be given not only to extending the number of women screened, but also to increasing the frequency of screening and to improving the clinical response to an abnormal smear. PMID- 2202698 TI - Haemolytic uraemic syndrome with shigella. AB - A 49-year-old male developed bloody diarrhoea whilst on a visit to India. Sigmoidoscopy and rectal biopsy showed acute colitis. Shigella dysentery type I was isolated from stool culture. Cytotoxin production by the organism was demonstrated. The patient developed acute renal failure, thrombocytopaenia and microangiopathic haemolytic anaemia. He required mechanical ventilation, haemodialysis, blood transfusion and antibiotic therapy and achieved a complete recovery. This is an unusual case of haemolytic uraemic syndrome complicating shigellosis in an adult. PMID- 2202699 TI - What's in a relationship? Sarcoidosis and tuberculosis. AB - The relationship between the two granulomatous diseases sarcoidosis and tuberculosis is reviewed. Data from 14 published case series are presented in the form of a figure which indicates that case series collected earlier in time and with a high proportion of non-white patients show a higher prevalence of tuberculosis. This high prevalence was also found in other chronic diseases such as diabetes and rheumatoid arthritis. The more frequent presence of mycobacteria in sarcoid than in control tissue, the parallel changes in the prevalence of sarcoidosis and tuberculosis in a community and the presence of myocbacteria on culture if pursued with sufficient aggression, are consistant with a mycobacterial aetiology. Recent developments in the immunology of the two diseases are reviewed. PMID- 2202700 TI - The technique of gait analysis using a Coda-3 motion analysis system. AB - Gait analysis using Code-3 provides information which allows individual gait to be characterised with little interference to the patient. It is an ideal method for analysing gait in patients with cerebral palsy. Because of the ease with which this information is now available using Coda-3, gait analysis can now be performed on all ambulant patients in whom surgery is contemplated. PMID- 2202702 TI - A gratifying multifaceted career. PMID- 2202701 TI - Fluorescent labeling of tRNA by 5-[2-(2-iodoacetamido) ethylamino]-1 naphthalenesulfonate (IAEDANS). PMID- 2202703 TI - Ultrasonographic diagnosis of obstructive uropathy in a caprine doe. AB - Abdominal ultrasonography was performed on a caprine doe with anorexia, dysuria, and a palpable abdominal mass. Ultrasonography of a large firm mass situated cranial to the pelvic brim revealed a distended urinary bladder, which was confirmed by a dynamic bubble study. The left kidney had a large anechoic renal medulla and dilated renal pelvis and ureter consistent with ureteropyelectasia. Necropsy confirmed the existence of hydronephrosis and hydroureter, as well as cystitis, pyelonephritis, and partial urinary tract obstruction. The cause of the obstructive uropathy was a mass of fibrous tissue that obliterated the uterine cervix and partially obstructed the urethra and left ureter. The cause was presumed to be a cervical trauma from dystocia and forced extraction of a kid, with subsequent chronic fibrosis. PMID- 2202704 TI - Comparison of some enrichment broths and growth media for the isolation of thermophilic campylobacters from surface water samples. AB - Three different enrichment broths and two selective growth media were compared for isolating thermophilic campylobacters by combined membrane filtration and enrichment techniques from surface waters of different physical, chemical and bacteriological characteristics. Fifty-two strains of campylobacters were isolated from total of 1668 cultures. The various broth/medium combinations did not affect the dominance of C. jejuni over C. coli (total 49 C. jejuni and three C. coli). The most efficient combinations of enrichment broth and growth media were either Oosterom broth/blood-free charcoal-cefoperazone-deoxycholate agar (CCDA) medium or blood-free charcoal-cefoperazone-deoxycholate (CCD) broth/CCDA medium. Modified Preston broth (sheep blood instead of horse blood) with either of the growth media gave significantly lower yields although it suppressed efficiently the growth of contaminants. Skirrow medium had lower selectivity than CCDA medium and gave slightly lower isolation rate. Enrichment time (24 or 48 h) did not affect the isolation frequency of campylobacters but longer enrichment time increased the growth of contaminants. Prefiltration through membranes of pore sizes 5.0 and 1.2 microns decreased the growth of contaminants. However, these membranes retain campylobacters and must be cultured to avoid underestimation. From more polluted waters campylobacters were isolated most frequently with CCD broth and CCDA medium. PMID- 2202705 TI - Randomised double blind placebo controlled clinical trial of sucralfate and ranitidine in chronic duodenal ulcer. AB - A double blind, randomised, placebo controlled clinical trial was carried out in endoscopically proved chronic duodenal ulcer patients to compare the efficacy of sucralfate and ranitidine. Sucralfate 1 g four times daily and ranitidine 150 mg twice daily were found to be equally effective in inducing ulcer healing (73.1% and 82.1% respectively) during the 6-week treatment period. The rate of recurrence of the ulcer within six months after the initial treatment (84.2% and 82.6%) was also comparable in the sucralfate and ranitidine groups. Sucralfate and ranitidine are equally effective in ulcer healing and prevention of ulcer relapse. PMID- 2202707 TI - Rapid control of diabetes mellitus. PMID- 2202706 TI - Portal hypertension therapy with oral propranolol. A short-term study. AB - Thirty patients were evaluated in a blind fashion to study the effect of oral propranolol on portal hypertension of varied aetiology. The dose of oral propranolol (administered to 15 patients) was adjusted to reduce the resting heart rate by approximately 25%. Splenic pulp pressure served as the parameter for portal pressure. A matched group of 15 control subjects on placebo was also studied. The mean portal pressure in the propranolol group fell from 3.49 to 2.69 kPa saline (P less than 0.001) as compared to the control group where the mean pressure increased from 3.57 to 3.63 kPa saline. The propranolol group showed improvement in clinical symptomatology with a significant reduction in body weight and abdominal girth in patients with ascites. A significant positive correlation (r = 0.78; p less than 0.007) was obtained between the fall in portal pressure and the initial levels. Thus, oral propranolol proved useful in the conservative management of portal hypertension of varied aetiology. PMID- 2202708 TI - Abnormalities in insulin response to intravenous glucose in offspring of conjugal (type 2) diabetic parents. AB - Glucose and insulin responses were measured during intravenous glucose tolerance test in 12 normal controls and 16 normoglycaemic adult offspring of conjugal diabetic parents. The glucose response curve and the glucose disposal rate in the offspring were not different from the normal pattern. These subjects elicited a lower first phase insulin (0-10 minutes area under the curve, p = 0.04), lower peak immunoreactive insulin response (p = 0.032) and also showed a delay in the first phase (p = 0.037) compared to control values. The second phase of insulin (11-120 minutes area) was not significantly different in the two groups. These changes could serve as early markers of diabetes in offspring of conjugal diabetic parents. PMID- 2202709 TI - Hepatopulmonary amoebiasis. Efficacy of various treatment regimens containing dehydroemetine and/or metronidazole. AB - Thirty three patients with hepatopulmonary amoebiasis were studied. Pulmonary involvement was observed in 55%, pleuro-pulmonary lesions in 30%. Typical chocolate coloured sputum was obtained in 24% and pleural fluid in 21% of patients. Entamoeba histolytica were demonstrable in the sputum in only 6% and in the pleural fluid in 15%. The best therapeutic results were obtained with a combination of dehydroemetine and metronidazole. However, metronidazole was found to be nearly as effective as dehydroemetine, and metronidazole 400 mg and 800 mg were equally effective. PMID- 2202710 TI - Autologous bone marrow transplantation (ABMT) in acute myelogenous leukaemia- Heidelberg experience. AB - Thirty-seven patients with acute myelogenous leukaemia, 17 in the first clinical remission (CR; low risk) and 20 in the second or subsequent CR (high risk), underwent total body irradiation (12.1-16.7 GY) and cyclophosphamide treatment (200 mg/kg), followed by autologous bone marrow transplantation. The autograft was incubated with the active cyclophosphamide derivative mafosfamide to reduce the number of possible contaminating clonogenic tumour cells. The transplant related death rate was low (8.1%). The probability of disease free survival after marrow transplantation in the first CR was 62% compared to 28% in the second or subsequent CR at a median follow up to 22 months. The survival plateau of low risk patients after transplantation seems to be stable with no relapses occurring more than one year later, whereas three late relapses were seen in high risk patients. PMID- 2202711 TI - Effects of purified insulins on insulin requirement and metabolic control. AB - Seventeen diabetics requiring high insulin doses were transferred from conventional insulin to purified chromatographed porcine insulins (Actrapid and Lentard-Novo, Denmark). At the end of 8 to 12 weeks, there was a 46% reduction in insulin dosage while metabolic control improved. Some of these patients when transferred again to conventional insulins demonstrated poor metabolic control and an increase in insulin requirements. Use of purified insulin is beneficial as insulin requirement is reduced with improved metabolic control. PMID- 2202712 TI - Smoking and hypertension: Indian scenario. AB - In a large multicentre study of 918 hypertensive patients, 28% of subjects were found to be smokers. Smokers had a higher average weight and associated diseases like coronary artery disease and diabetes. It is suggested that higher incidence of coronary artery disease and diabetes in the hypertensive smokers carries a higher risk of further cardiovascular events. PMID- 2202713 TI - Spontaneous bacterial peritonitis in cirrhosis with ascites. PMID- 2202714 TI - Acute suppurative thyroiditis. Report of the cases. PMID- 2202715 TI - Insulin requirement formula. PMID- 2202716 TI - Purification of mouse Ren 2 prorenin produced in Chinese hamster ovary cells. AB - Renin is produced from a larger, inactive precursor, prorenin, by endoproteolytic removal of the amino-terminal prosegment. In this study, we have transfected Chinese hamster ovary cells with the expression plasmid of mouse Ren 2 preprorenin, and have purified mouse Ren 2 prorenin from the incubation medium of these cells by DEAE-Toyopearl chromatography, Blue-Toyopearl chromatography, and isoelectric focusing. Prorenin thus purified has a molecular mass of 42 kDa as determined by SDS-PAGE and an isoelectric point of 6.5. Amino-terminal sequencing has demonstrated that the purified prorenin has the amino-terminus predicted from the nucleotide sequence of mouse Ren 2 preprorenin cDNA. PMID- 2202717 TI - Protein export in bacteria: an overview. PMID- 2202718 TI - Biophysical studies of signal peptides: implications for signal sequence functions and the involvement of lipid in protein export. AB - This review discusses efforts to understand the mode of action of signal sequences by biophysical study of synthetic peptides corresponding to these protein localization signals. On the basis of reports from several laboratories, it is now clear that signal peptides may adopt a variety of conformations, depending on their local environment. In membrane-mimetic systems like detergent micelles or lipid vesicles, they have a high tendency to form alpha helices. Ability to take up a helical conformation appears to be required at some point in the function of a signal sequence, since some peptides corresponding to export defective signal sequences display reduced helical potential. By contrast, functional signal sequences share a high capacity to adopt alpha helices. High affinity for organized lipid assemblies, like monolayers or vesicles, is also a property of functional signal sequences. This correlation suggests a role for direct interaction of signal sequences with the lipids of the cytoplasmic membrane in vivo. Supporting this role are studies of the influence of signal peptides on lipid structure, which reveal an ability of these peptides to perturb lipid packing and to alter the phase state of the lipids. Insertion of the signal sequence in vivo could substantially reduce the barrier for translocation of the mature chain. Lastly, synthetic signal peptides have been added to native membranes and found to inhibit translocation of precursor proteins. This approach bridges the biophysical and the biochemical aspects of protein export and promises to shed light on the functional correlates of the properties and interactions observed in model systems. PMID- 2202719 TI - Signal peptide mutants of Escherichia coli. AB - Numerous secretory proteins of the Gram-negative bacteria E. coli are synthesized as precursor proteins which require an amino terminal extension known as the signal peptide for translocation across the cytoplasmic membrane. Following translocation, the signal peptide is proteolytically cleaved from the precursor to produce the mature exported protein. Signal peptides do not exhibit sequence homology, but invariably share common structural features: (1) The basic amino acid residues positioned at the amino terminus of the signal peptide are probably involved in precursor protein binding to the cytoplasmic membrane surface. (2) A stretch of 10 to 15 nonpolar amino acid residues form a hydrophobic core in the signal peptide which can insert into the lipid bilayer. (3) Small residues capable of beta-turn formation are located at the cleavage site in the carboxyl terminus of the signal peptide. (4) Charge characteristics of the amino terminal region of the mature protein can also influence precursor protein export. A variety of mutations in each of the structurally distinct regions of the signal peptide have been constructed via site-directed mutagenesis or isolated through genetic selection. These mutants have shed considerable light on the structure and function of the signal peptide and are reviewed here. PMID- 2202720 TI - Signal peptidases and signal peptide hydrolases. AB - Signal peptidases, the endoproteases that remove the amino-terminal signal sequence from many secretory proteins, have been isolated from various sources. Seven signal peptidases have been purified, two from E. coli, two from mammalian sources, and three from mitochondrial matrix. The mitochondrial enzymes are soluble and function as a heterogeneous dimer. The mammalian enzymes are isolated as a complex and share a common glycosylated subunit. The bacterial enzymes are isolated as monomers and show no sequence homology with each other or the mammalian enzymes. The membrane-bound enzymes seem to require a substrate containing a consensus sequence following the -3, -1 rule of von Heijne at the cleavage site; however, processing of the substrate is strongly influenced by the hydrophobic region of the signal peptide. The enzymes appear to recognize an unknown three-dimensional motif rather than a specific amino acid sequence around the cleavage site. The matrix mitochondrial enzymes are metallo-endopeptidases; however, the other signal peptidases may belong to a unique class of proteases as they are resistant to chelators and most protease inhibitors. There are no data concerning the substrate binding site of these enzymes. In vivo, the signal peptide is rapidly degraded. Three different enzymes in Escherichia coli that can degrade a signal peptide in vitro have been identified. The intact signal peptide is not accumulated in mutants lacking these enzymes, which suggests that these peptidases individually are not responsible for the degradation of an intact signal peptide in vivo. It is speculated that signal peptidases and signal peptide hydrolases are integral components of the secretory pathway and that inhibition of the terminal steps can block translocation. PMID- 2202721 TI - The sec and prl genes of Escherichia coli. AB - Two general approaches have been used to define genetically the genes that encode components of the cellular protein export machinery. One of these strategies identifies mutations that confer a conditional-lethal, pleiotropic export defect (sec, secretion). The other identifies dominant suppressors of signal sequence mutations (prl, protein localization). Subsequent characterization reveals that in at least three cases, prlA/secY, prlD/secA, and prlG/secE, both types of mutations are found within the same structural gene. This convergence is satisfying and provides compelling evidence for direct involvement of these gene products in the export process. PMID- 2202722 TI - SecB protein: a cytosolic export factor that associates with nascent exported proteins. AB - Soluble factors participate in protein translocation across a variety of biological membranes. The Escherichia coli soluble protein SecB (the product of the secB gene) is involved in the export of periplasmic and outer membrane proteins. The isolation of secB mutations permitted the demonstration that SecB is required for rapid and efficient export of certain proteins. Consistent with the results of these genetic studies, purified SecB has been shown to stimulate protein translocation across E. coli inner membrane vesicles in vitro. This article presents a review of these past studies of SecB, speculation on the role of SecB in protein translocation, and a comparison of SecB and other factors, trigger factor and GroEL. PMID- 2202723 TI - Structure, function, and biogenesis of SecY, an integral membrane protein involved in protein export. AB - The E. coli secY (prlA) gene, located in the operator-distal part of the spc ribosomal protein operon, codes for an integral membrane protein, SecY. The phenotypes of temperature-sensitive and cold-sensitive mutations in secY suggest that the SecY protein plays an essential role in vivo to facilitate protein translocation, whereas the prlA mutations in this gene suggest that SecY may interact with the signal sequence of translocating polypeptides. SecY contains most probably six cytoplasmic and five periplasmic domains, as well as 10 transmembrane segments. Such membrane-embedded structure may confer the SecY protein a "translocator" function, in which it provides a protein-aceous pathway for passage of secreted as well as membrane proteins. Results obtained by in vitro analyses of the translocation reactions, as well as some new phenotypes of the secY mutants, are consistent with this notion. Possible interaction of SecY with other secretion and chaperone-like factors is also discussed. PMID- 2202724 TI - In vitro translocation of bacterial secretory proteins and energy requirements. AB - The recent establishment of in vitro assay systems has made biochemical studies on the process of membrane translocation of secretory proteins possible. This review summarizes what we have learned, using these in vitro systems, concerning the biochemical process of protein translocation, with special reference to energy requirements. Both ATP and the protonmotive force participate in the translocation reaction. The requirement of ATP is obligatory, whereas that of the protonmotive force differs, in terms of its level, with the secretory protein species. The possible roles of ATP and the protonmotive force in protein translocation are discussed with special reference to the function of SecA, an essential component of the secretory machinery. The effect of positive charges, which precede or follow the hydrophobic domain of signal peptides, on translocation is also discussed. PMID- 2202726 TI - Export and sorting of the Escherichia coli outer membrane protein OmpA. AB - Results of studies, mostly using the outer membrane, 325 residue protein OmpA, are reviewed which concern its translocation across the plasma membrane and incorporation into the outer membrane of Escherichia coli. For translocation, neither a unique export signal, acting in a positive fashion within the mature part of the precursor, nor a unique conformation of the precursor is required. Rather, the mature part of a secretory protein has to be export-compatible. Export-incompatibility can be caused by a stretch of 16 (but not 8 or 12) hydrophobic residues, too low a size of the polypeptide (smaller than 75 residue precursors), net positive charge at the N-terminus, or lack of a turn potential at the same site. It is not yet clear whether binding sites for chaperonins (SecB, trigger factor, GroEL) within OmpA are important in vivo. The mechanism of sorting of outer membrane proteins is not yet understood. The membrane part of OmpA, encompassing residues 1 to about 170, it thought to traverse the membrane eight times in antiparallel beta-sheet conformation. At least the structure of the last beta-strand (residues 160-170) is of crucial importance for membrane assembly. It must be amphiphilic or hydrophobic, these properties must extend over at least nine residues, and it must not contain a proline residue at or near its center. Membrane incorporation of OmpA involves a conformational change of the protein and it could be that the last beta-strand initiates folding and assembly in the outer membrane. PMID- 2202725 TI - Export of the periplasmic maltose-binding protein of Escherichia coli. AB - The export of the maltose-binding protein (MBP), the malE gene product, to the periplasm of Escherichia coli cells has been extensively investigated. The isolation of strains synthesizing MalE-LacZ hybrid proteins led to a novel genetic selection for mutants that accumulate export-defective precursor MBP (preMBP) in the cytoplasm. The export defects were subsequently shown to result from alterations in the MBP signal peptide. Analysis of these and a variety of mutants obtained in other ways has provided considerable insight into the requirements for an optimally functional MBP signal peptide. This structure has been shown to have multiple roles in the export process, including promoting entry of preMBP into the export pathway and initiating MBP translocation across the cytoplasmic membrane. The latter has been shown to be a late event relative to synthesis and can occur entirely posttranslationally, even many minutes after the completion of synthesis. Translocation requires that the MBP polypeptide exist in an export-competent conformation that most likely represents an unfolded state that is not inhibitory to membrane transit. The signal peptide contributes to the export competence of preMBP by slowing the rate at which the attached mature moiety folds. In addition, preMBP folding is thought to be further retarded by the binding of a cytoplasmic protein, SecB, to the mature moiety of nascent preMBP. In cells lacking this antifolding factor, MBP export represents a race between delivery of newly synthesized, export-competent preMBP to the translocation machinery in the cytoplasmic membrane and folding of preMBP into an export-incompetent conformation. SecB is one of three E. coli proteins classified as "molecular chaperones" by their ability to stabilize precursor proteins for membrane translocation. PMID- 2202727 TI - Lipoproteins in bacteria. AB - Covalent modification of membrane proteins with lipids appears to be ubiquitous in all living cells. The major outer membrane (Braun's) lipoprotein of E. coli, the prototype of bacterial lipoproteins, is first synthesized as a precursor protein. Analysis of signal sequences of 26 distinct lipoprotein precursors has revealed a consensus sequence of lipoprotein modification/processing site of Leu (Ala, Ser)-(Gly, Ala)-Cys at -3 to +1 positions which would represent the cleavage region of about three-fourth of all lipoprotein signal sequences in bacteria. Unmodified prolipoprotein with the putative consensus sequence undergoes sequential modification and processing reactions catalyzed by glyceryl transferase, O-acyl transferase(s), prolipoprotein signal peptidase (signal peptidase II), and N-acyl transferase to form mature lipoprotein. Like all exported proteins, the export of lipoprotein requires functional SecA, SecY, and SecD proteins. Thus all precursor proteins are exported through a common pathway accessible to both signal peptidase I and signal peptidase II. The rapidly increasing list of lipid-modified proteins in both prokaryotic as well as eukaryotic cells indicates that lipoproteins comprise a diverse group of structurally and functionally distinct proteins. They share a common structural feature which is derived from a common biosynthetic pathway. PMID- 2202728 TI - The mechanism of secretion of hemolysin and other polypeptides from gram-negative bacteria. AB - In the secretion of polypeptides from Gram-negative bacteria, the outer membrane constitutes a specific barrier which has to be circumvented. In the majority of systems, secretion is a two-step process, with initial export to the periplasm involving an N-terminal signal sequence. Transport across the outer membrane then involves a variable number of ancillary polypeptides including both periplasmic and outer membrane. While such ancillary proteins are probably specific for each secreted protein, the mechanism of movement across the outer membrane is unknown. In contrast to these systems, secretion of the E. coli hemolysin (HlyA) has several distinctive features. These include a novel targeting signal located within the last 50 or so C-terminal amino acids, the absence of any periplasmic intermediates in transfer, and a specific membrane-bound translocator, HlyB, with important mammalian homologues such as P-glycoprotein (Mdr) and the cystic fibrosis protein. In this review we discuss the nature of the HlyA targeting signal, the structure and function of HlyB, and the probability that HlyA is secreted directly to the medium through a trans-envelope complex composed of HlyB and HlyD. PMID- 2202730 TI - DNA repair at the level of the gene: molecular and clinical considerations. AB - DNA repair is an important process. It is as essential for the cell as is transcription and replication. There is evidence that deficient DNA repair processes lead to human disease including cancer, and recent progress in the field of DNA repair is likely to expand our knowledge about these relationships considerably. One recent advance is our capability to analyze the fine structure of DNA damage and repair by measuring the formation of lesions and their repair in specific, important genes in rodent and human cells. Such studies are leading to increased understanding of the molecular and clinical aspects of DNA repair. PMID- 2202729 TI - Application of molecular cytogenetic techniques to the evaluation of renal parenchymal tumors. AB - This guest editorial discusses the molecular cytogenetic features of human renal parenchymal tumors with an emphasis on their diagnostic usefulness. Important contributions of this review are discrimination (a) between papillary and nonpapillary renal cell carcinomas and (b) between tubulopapillary adenomas and papillary carcinomas. Speculations regarding the histogenesis of different renal parenchymal tumors are presented, with the hope that they may serve to diminish some of the confusion surrounding the classification of these tumors. PMID- 2202731 TI - Comparative effect of cisplatin, spiroplatin, carboplatin and iproplatin in a human tumor clonogenic assay. AB - A modified double-layer Hamburger and Salmon cloning assay was used to test cisplatin and its analogs (spiroplatin, carboplatin and iproplatin) on fresh tumor samples from 63 patients with a variety of non-hematological malignancies. Among them were 18 breast cancers, 17 ovarian cancers and 7 of unknown primaries. Half the patients received prior chemotherapy. Cisplatin regimens were given in 16 cases. When possible, cells were exposed for 1 h to each drug in concentrations of 0.1 microgram/ml and 1.0 microgram/ml for cisplatin and spiroplatin, 1.0 microgram/ml and 10 micrograms/ml for carboplatin and iproplatin. A greater than or equal to 50% cell kill with at least one drug was found in 20 samples including 8 ovarian cancers, 3 breast cancers and 1 unknown primary. A greater than or equal to 70% cell kill was seen in 2 samples with cisplatin, 3 with spiroplatin and carboplatin, and 6 with iproplatin. There was only partial cross-resistance between cisplatin and its analogs. Among 57 paired comparisons of cisplatin with spiroplatin, 2 showed drug sensitivity to cisplatin alone, 6 to spiroplatin alone, and 6 to both. The same sort of observation was made with carboplatin. The lack of cross-resistance between cisplatin and iproplatin was particularly striking: among 53 pairs, 6 were sensitive to cisplatin alone, 8 to iproplatin alone, and 2 to both. About 20% of the samples that were resistant to cisplatin were sensitive to iproplatin. Our data show hints of activity in breast and ovarian cancers with all analogs and suggest that they will achieve clinical antitumor activity similar to that they will achieve clinical antitumor activity similar to that of cisplatin. The in vitro evidence of incomplete cross-resistance between cisplatin and its analogs should be investigated further. PMID- 2202732 TI - Lamins A and C bind and assemble at the surface of mitotic chromosomes. AB - To study a possible interaction of nuclear lamins with chromatin, we examined assembly of lamins A and C at mitotic chromosome surfaces in vitro. When a postmicrosomal supernatant of metaphase CHO cells containing disassembled lamins A and C is incubated with chromosomes isolated from mitotic Chinese hamster ovary cells, lamins A and C undergo dephosphorylation and uniformly coat the chromosome surfaces. Furthermore, when purified rat liver lamins A and C are dialyzed with mitotic chromosomes into a buffer of physiological ionic strength and pH, lamins A and C coat chromosomes in a similar fashion. In both cases a lamin-containing supramolecular structure is formed that remains intact when the chromatin is removed by digestion with micrococcal nuclease and extraction with 0.5 M KCl. Lamins associate with chromosomes at concentrations approximately eightfold lower than the critical concentration at which they self-assemble into insoluble structures in the absence of chromosomes, indicating that chromosome surfaces contain binding sites that promote lamin assembly. These binding sites are destroyed by brief treatment of chromosomes with trypsin or micrococcal nuclease. Together, these data suggest the existence of a specific lamin-chromatin interaction in cells that may be important for nuclear envelope reassembly and interphase chromosome structure. PMID- 2202733 TI - Control of actin filament length by phosphorylation of fragmin-actin complex. AB - Fragmin is a Ca2(+)-sensitive F-actin-severing protein purified from a slime mold, Physarum polycephalum (Hasegawa, T., S. Takahashi, H. Hayashi, and S. Hatano. 1980. Biochemistry. 19:2677-2683). It binds to G-actin to form a 1:1 fragmin/actin complex in the presence of micromolar free Ca2+. The complex nucleates actin polymerization and caps the barbed end of the short F-actin (Sugino, H., and S. Hatano. 1982. Cell Motil. 2:457-470). Subsequent removal of Ca2+, however, hardly dissociates the complex. This complex nucleates actin polymerization and caps the F-actin regardless of Ca2+ concentration. Here we report that this activity of fragmin-actin complex can be abolished by phosphorylation of actin of the complex. When crude extract from Physarum plasmodium was incubated with 5 mM ATP and 1 mM EGTA, the activities of the complex decreased to a great extent. The inactivation of the complex in the crude extract was not observed in the presence of Ca2+. In addition, the activities of the complex inactivated in the crude extract were restored under conditions suitable for phosphatase reactions. We purified factors that inactivated fragmin actin complex from the crude extract. These factors phosphorylated actin of the complex, and the activities of the complex decreased with an increased level of phosphorylation of the complex. These factors, termed actin kinase, also inactivated the complex that capped the barbed end of short F-actin, leading to elongation of the short F-actin to long F-actin. Thus the length of F-actin can be controlled by phosphorylation of fragmin-actin complex by actin kinase. PMID- 2202735 TI - Direct demonstration of the lectin activity of gp90MEL, a lymphocyte homing receptor. AB - Considerable evidence implicates gp90MEL as a lymphocyte homing receptor mediating lymphocyte attachment to high endothelial venules of lymph nodes in mouse. The protein appears to function as a calcium-dependent, lectin-like receptor as inferred primarily by the ability of specific carbohydrates to block its function and by the presence of a calcium-type lectin domain in its primary sequence. An ELISA assay is described which provides the first demonstration that the isolated protein has lectin activity and allows a further definition of its carbohydrate specificity. In addition to the monosaccharides mannose-6-phosphate and fructose-1-phosphate, ligand activity is shown for the sulfated glycolipid, sulfatide, and for two sulfated fucose-containing polysaccharides (fucoidin and egg jelly coat) from nonmammalian sources. PMID- 2202734 TI - Use of DNA sequence and mutant analyses and antisense oligodeoxynucleotides to examine the molecular basis of nonmuscle myosin light chain kinase autoinhibition, calmodulin recognition, and activity. AB - The first primary structure for a nonmuscle myosin light chain kinase (nmMLCK) has been determined by elucidation of the cDNA sequence encoding the protein kinase from chicken embryo fibroblasts, and insight into the molecular mechanism of calmodulin (CaM) recognition and activation has been obtained by the use of site-specific mutagenesis and suppressor mutant analysis. Treatment of chicken and mouse fibroblasts with antisense oligodeoxynucleotides based on the cDNA sequence results in an apparent decrease in MLCK levels, an altered morphology reminiscent of that seen in v-src-transformed cells, and a possible effect on cell proliferation. nmMLCK is distinct from and larger than smooth muscle MLCK (smMLCK), although their extended DNA sequence identity is suggestive of a close genetic relationship not found with skeletal muscle MLCK. The analysis of 20 mutant MLCKs indicates that the autoinhibitory and CaM recognition activities are centered in distinct but functionally coupled amino acid sequences (residues 1,068-1,080 and 1,082-1,101, respectively). Analysis of enzyme chimeras, random mutations, inverted sequences, and point mutations in the 1,082-1,101 region demonstrates its functional importance for CaM recognition but not autoinhibition. In contrast, certain mutations in the 1,068-1,080 region result in a constitutively active MLCK that still binds CaM. These results suggest that CaM/protein kinase complexes use similar structural themes to transduce calcium signals into selective biological responses, demonstrate a direct link between nmMLCK and non-muscle cell function, and provide a firm basis for genetic studies and analyses of how nmMLCK is involved in development and cell proliferation. PMID- 2202736 TI - The tight junction protein ZO-1 is concentrated along slit diaphragms of the glomerular epithelium. AB - The foot processes of glomerular epithelial cells of the mammalian kidney are firmly attached to one another by shallow intercellular junctions or slit diaphragms of unknown composition. We have investigated the molecular nature of these junctions using an antibody that recognizes ZO-1, a protein that is specific for the tight junction or zonula occludens. By immunoblotting the affinity purified anti-ZO-1 IgG recognizes a single 225-kD band in kidney cortex and in slit diaphragm-enriched fractions as in other tissues. When ZO-1 was localized by immunofluorescence in kidney tissue of adult rats, the protein was detected in epithelia of all segments of the nephron, but the glomerular epithelium was much more intensely stained than any other epithelium. Among tubule epithelia the signal for ZO-1 correlated with the known fibril content and physiologic tightness of the junctions, i.e., it was highest in distal and collecting tubules and lowest in the proximal tubule. By immunoelectron microscopy ZO-1 was found to be concentrated on the cytoplasmic surface of the tight junctional membrane. Within the glomerulus ZO-1 was localized predominantly in the epithelial foot processes where it was concentrated precisely at the points of insertion of the slit diaphragms into the lateral cell membrane. Its distribution appeared to be continuous along the continuous slit membrane junction. When ZO-1 was localized in differentiating glomeruli in the newborn rat kidney, it was present early in development when the apical junctional complexes between presumptive podocytes are composed of typical tight and adhering junctions. It remained associated with these junctions during the time they migrate down the lateral cell surface, disappear and are replaced by slit diaphragms. The distribution of ZO-1 and the close developmental relationship between the two junctions suggest that the slit diaphragm is a variant of the tight junction that shares with it at least one structural protein and the functional property of defining distinctive plasmalemmal domains. The glomerular epithelium is unique among renal epithelia in that ZO-1 is present, but the intercellular spaces are wide open and no fibrils are seen by freeze fracture. The presence of ZO-1 along slit membranes indicates that expression of ZO-1 alone does not lead to tight junction assembly. PMID- 2202737 TI - Identification of an Arg-Gly-Asp (RGD) cell adhesion site in human immunodeficiency virus type 1 transactivation protein, tat. AB - Tat, the transactivation factor of human immunodeficiency virus type 1 (HIV-1), contains the highly conserved tripeptide sequence Arg-Gly-Asp (RGD) that characterizes sites for integrin-mediated cell adhesion. The tat protein was assayed for cell attachment activity by measuring the adhesion of monocytic, T lymphocytic, and skeletal muscle-derived cell lines to tat-coated substratum. All cell lines tested bound to tat in a dose-dependent manner and the tat cell adhesion required the RGD sequence because tat mutants constructed to contain an RGE or KGE tripeptide sequence did not mediate efficient cell adhesion. The tat mediated cell attachment also required divalent cations and an intact cytoskeleton. In addition, cell adhesion to tat was inhibited in the presence of an RGD-containing peptide GRGDSPK or an anti-tat mAb that recognizes the RGD epitope. These results strongly suggest that cells are bound to tat through an integrin. Interestingly, myoblast cells bound to tat remained round, whereas the same cells attached through an integrin for a matrix protein typically flatten and spread. The role of this RGD-dependent cellular adhesion of tat in HIV-1 infection remains to be determined. PMID- 2202739 TI - Temperature-sensitive yeast mutants defective in mitochondrial inheritance. AB - The distribution of mitochondria to daughter cells is an essential feature of mitotic cell growth, yet the molecular mechanisms facilitating this mitochondrial inheritance are unknown. We have isolated mutants of Saccharomyces cerevisiae that are temperature-sensitive for the transfer of mitochondria into a growing bud. Two of these mutants contain single, recessive, nuclear mutations, mdm1 and mdm2, that cause temperature-sensitive growth and aberrant mitochondrial distribution at the nonpermissive temperature. The absence of mitochondria from the buds of mutant cells was confirmed by indirect immunofluorescence microscopy and by transmission electron microscopy. The mdm1 lesion also retards nuclear division and prevents the transfer of nuclei into the buds. Cells containing the mdm2 mutation grown at the nonpermissive temperature sequentially form multiple buds, each receiving a nucleus but no mitochondria. Neither mdm1 or mdm2 affects the transfer of vacuolar material into the buds or causes apparent changes in the tubulin- or actin-based cytoskeletons. The mdm1 and mdm2 mutations are cell-cycle specific, displaying an execution point in late G1 or early S phase. PMID- 2202738 TI - Molecular analysis of the yeast VPS3 gene and the role of its product in vacuolar protein sorting and vacuolar segregation during the cell cycle. AB - vps3 mutants of the yeast Saccharomyces cerevisiae are impaired in the sorting of newly synthesized soluble vacuolar proteins and in the acidification of the vacuole (Rothman, J. H., and T. H. Stevens. Cell. 47:1041-1051; Rothman, J. H., C. T. Yamashiro, C. K. Raymond, P. M. Kane, and T. H. Stevens. 1989. J. Cell Biol. 109:93-100). The VPS3 gene, which was cloned using a novel selection procedure, encodes a low abundance, hydrophilic protein of 117 kD that most likely resides in the cytoplasm. Yeast strains bearing a deletion of the VPS3 gene (vps3-delta 1) are viable, yet their growth rate is significantly reduced relative to wild-type cells. Temperature shift experiments with strains carrying a temperature conditional vps3 allele demonstrate that cells rapidly lose the capacity to sort the vacuolar protein carboxypeptidase Y upon loss of VPS3 function. Vacuolar morphology was examined in wild-type and vps3-delta 1 yeast strains by fluorescence microscopy. The vacuoles in wild-type yeast cells are morphologically complex, and they appear to be actively partitioned between mother cells and buds during an early phase of bud growth. Vacuolar morphology in vps3-delta 1 mutants is significantly altered from the wild-type pattern, and the vacuolar segregation process seen in wild-type strains is defective in these mutants. With the exception of a vacuolar acidification defect, the phenotypes of vps3-delta 1 strains are significantly different from those of mutants lacking the vacuolar proton-translocating ATPase. These data demonstrate that the acidification defect in vps3-delta 1 cells is not the primary cause of the pleiotropic defects in vacuolar function observed in these mutants. PMID- 2202741 TI - Human recombinant interleukin-1 beta- and tumor necrosis factor alpha-mediated suppression of heparin-like compounds on cultured porcine aortic endothelial cells. AB - Cytokines are known to tip the balance of the coagulant-anticoagulant molecules on the endothelial cell surface toward intravascular coagulation. Their effects on endothelial cell surface-associated heparin-like compounds have not been examined yet. Incorporation of [35S]sulfate into heparan sulfate on cultured porcine aortic endothelial cells was suppressed by human recombinant interleukin 1 beta (rIL-1 beta) or tumor necrosis factor alpha (rTNF alpha) in a dose- and time-dependent manner with little effect on cell number, protein content, and [3H]leucine incorporation of cells. Maximal inhibition was achieved by incubation of cells with 100 ng/ml of rIL-1 beta or 5 ng/ml of rTNF alpha for 12-24 hours, resulting in a reduction of the synthesis of heparan sulfate on the cell surface by approximately 50%. The dose dependency was consistent with that seen in the stimulation of endothelial cell procoagulant activity by each cytokine. The suppression of heparan sulfate synthesis was sustained for at least 48 hours after pretreatment of cells with cytokines and was unchanged after the addition of indomethacin or polymyxin B. The rate of degradation of prelabeled 35S-heparan sulfate on the cell surface was not altered by cytokine treatments. Neither the size, the net negative charge, nor the proportion of the molecule with high affinity for antithrombin III of endothelial cell heparan sulfate was changed by cytokines. Furthermore, specific binding of 125I-labeled antithrombin III to the endothelial cell surface was reduced to 40-60% of control by cytokines. In parallel with reduction in binding, antithrombin III cofactor (heparin-like) activity was partially diminished in cytokine-treated endothelial cells. Thus, cytokine-mediated suppression of heparin-like substance on endothelial cells appears to be another cytokine-inducible endothelial effects affecting coagulation. PMID- 2202740 TI - Distinct transport vesicles mediate the delivery of plasma membrane proteins to the apical and basolateral domains of MDCK cells. AB - Immunoisolation techniques have led to the purification of apical and basolateral transport vesicles that mediate the delivery of proteins from the trans-Golgi network to the two plasma membrane domains of MDCK cells. We showed previously that these transport vesicles can be formed and released in the presence of ATP from mechanically perforated cells (Bennett, M. K., A. Wandinger-Ness, and K. Simons, 1988. EMBO (Euro. Mol. Biol. Organ.) J. 7:4075-4085). Using virally infected cells, we have monitored the purification of the trans-Golgi derived vesicles by following influenza hemagglutinin or vesicular stomatitis virus (VSV) G protein as apical and basolateral markers, respectively. Equilibrium density gradient centrifugation revealed that hemagglutinin containing vesicles had a slightly lower density than those containing VSV-G protein, indicating that the two fractions were distinct. Antibodies directed against the cytoplasmically exposed domains of the viral spike glycoproteins permitted the resolution of apical and basolateral vesicle fractions. The immunoisolated vesicles contained a subset of the proteins present in the starting fraction. Many of the proteins were sialylated as expected for proteins existing the trans-Golgi network. The two populations of vesicles contained a number of proteins in common, as well as components which were enriched up to 38-fold in one fraction relative to the other. Among the unique components, a number of transmembrane proteins could be identified using Triton X-114 phase partitioning. This work provides evidence that two distinct classes of vesicles are responsible for apical and basolateral protein delivery. Common protein components are suggested to be involved in vesicle budding and fusion steps, while unique components may be required for specific recognition events such as those involved in protein sorting and vesicle targeting. PMID- 2202742 TI - Nuclear localization of 68 kDa calmodulin-binding protein is associated with the onset of DNA replication. AB - In Chinese hamster embryo fibroblast cells, an increase in intracellular calmodulin levels coincided with the nuclear localization of a calmodulin-binding protein of about 68 kDa as the cells progressed from G1 to S phase. When cells were limited from entering into S phase, by omitting insulin a defined medium, intracellular CaM levels did not increase and the 68 kDa calmodulin-binding protein was completely absent from the nuclei. Corresponding to the nuclear localization of calmodulin and the 68 kDa calmodulin-binding protein in S phase cells, there was a dramatic increase in DNA polymerase and thymidine kinase activities in the nuclei of S phase cells as compared to G1 phase cells. In addition, the 68 kDa calmodulin-binding protein, along with calmodulin, is observed to be an integral component of replitase complex responsible for nuclear DNA replication in S phase cells. These observations point to the association of calmodulin and calmodulin-binding protein(s) with the replication machinery responsible for nuclear DNA replication during S phase. A possible regulatory role of these proteins in the onset of DNA replication and cell proliferation is discussed. PMID- 2202743 TI - Role of extracellular signaling on endothelial cell proliferation and protein N glycosylation. AB - In vitro studies of angiogenic phenomenon have been limited due to nonavailability of a simple and biologically relevant model of the capillary wall. Recent development of a capillary endothelial cell line from the vascular bed of bovine adrenal medulla made us to study the effect of heparin, thrombin, thyroxine, glucagon, insulin, and phorbol myristate acetate (PMA) on the proliferative and metabolic activities such as glycosylation of asparagine-linked glycoproteins of these cells in culture. Out of six different agents studied here, only heparin, thrombin, and thyroxine reduced the doubling time of these cells by 24 hr with no observed morphological abnormality. Glucagon, showed marginal reduction in the cell doubling time. By contrast, insulin and PMA enhanced the doubling time. Insulin treatment though induced the S phase of cell cycle but it blocked the cells entry into the G2 + M phase. PMA arrested the cells in G0/G1 phase. The cellular response to protein N-glycosylation is increased in the presence of thyroxine, insulin, and thrombin and the effect is dose dependent. Further analysis on SDS-PAGE indicated that glycosylation of 80 120 kDa and 43 kDa glycoprotein species are enhanced when these cells are treated with insulin and thrombin. Glycopeptide generated from these glycoproteins suggested that they all carry "high mannose" and "complex" type oligosaccharide chains attached to their protein core. PMID- 2202744 TI - Antibiotics in periodontal therapy: advantages and disadvantages. AB - Antibiotic treatment of periodontitis aims at eradicating or controlling specific pathogens. Prime candidates for antibiotic therapy are patients with recently diagnosed active periodontitis or a history of recurrent disease who fail to stabilize following mechanical/surgical therapy. Since a variety of microbes with differing antimicrobial susceptibility profiles may cause periodontitis, selection of antimicrobial agents should be based on proper microbial diagnosis and sensitivity testing, as well as consideration of the patient's medical status. The risk of treating chemotherapeutically solely on the basis of clinical features, radiographic findings or a limited microbiological analysis, is failure to control the pathogens or overgrowth of new pathogens. A review of published papers reveals that appropriate systemic antibiotic therapy may enhance healing in patients with recent or high risk of periodontal breakdown. Systemic antibiotic therapy seems more predictable than topical administration in eradicating periodontal pathogens from deep periodontal pockets. Several promising antimicrobial agents for periodontitis treatment need testing in placebo-controlled, double-blind, randomized clinical trials. PMID- 2202745 TI - Cardiovascular infections: bacterial endocarditis of oral origin. Pathogenesis and prophylaxis. AB - The diagnosis infective endocarditis describes infection of the endocardial surface of the heart and indicates the presence of micro-organisms in the lesion. In most cases, the heart valves are affected, but the disease can also occur on septal defects or on the mural endocardium. The disease has been classified as acute or subacute based on the progression of the untreated disease. The acute form has a fulminant course with high fever and leukocytosis with death in less than 6 weeks. It is most often associated with infections caused by Staphylococcus aureus, Streptococcus pneumoniae or Streptococcus pyogenes. The subacute (death within 6 weeks to 3 months) and chronic (death more than 3 months) forms are mostly described together. These forms usually occur in patients with prior valvular disease and are characterized by a slow, indolent course with low-grade fever, night sweats, and weight loss. This form is usually caused by the viridansstreptococci. The above mentioned classification does not include the nonbacterial forms of endocarditis and enterococci often give rise to a disease intermediate between acute and subacute endocarditis. It is preferable to have a classification based on the micro-organism responsible since this classification has implications for the course followed and the appropriate antimicrobial agent to use. The clinical manifestations of the disease are so varied that they may be encountered in most medical subspecialities. Successful management is also dependent on the close cooperation of medical and dental disciplines. PMID- 2202746 TI - Vascular diseases and oral infections. AB - Vascular diseases are multifactorial, and several risk factors, such as increasing age, male sex, hypertension, diabetes, dyslipidemias and smoking, are well-known. In recent studies, associations have also been found between preceding infections and development of myocardial or cerebral infarction. Preceding acute respiratory infections are reported to be more common in patients with myocardial or cerebral infarction. Cerebral infarction may follow infective endocarditis, bacterial meningitis or any other bacteremic infection. Oral infections are common chronic bacterial infections. Although oral infections are local, they may lead to systemic infectious complications via stransient bacteremias, and there may also be other systemic effects, for instance, via immunologic or toxic mechanisms. Association between oral infections and vascular diseases has been studied in 2 Finnish case-control studies concerning myocardial and cerebral infarction. In these case-control studies, it was found that oral infections were more common in patients with myocardial or cerebral infarction than in their age- and sex-matched community controls. There are many factors, such as diabetes, smoking and alcohol abuse, which may predispose to both development of infarction and oral infections. Therefore, the observed association between oral infections and vascular diseases may result from these common predisposing factors, and causality between them cannot be inferred. There are, however, several possible links between oral infections and infarction. Although causality between oral infections and infarction cannot be proven, patients who have poor oral health need health education, paying attention to those common risk factors of oral infections and vascular diseases. Furthermore, their oral infections should be treated, because they may predispose to infectious complications, which may lead to infarction. PMID- 2202747 TI - Oral infections in immunocompromised patients. AB - The number of immunocompromised patients has increased during recent years, mainly because of more aggressive anti-cancer treatment and increased survival periods for end-stage cancer patients. Congenital and acquired immunodeficiencies are also more frequently recognized in dental practice due to increased diagnostic knowledge and increased numbers of HIV-infected persons. Oral complications and infections are related to the type and severeness of the immunodeficiency. Low amounts of immunoglobulins are known to play a role in many bacterial infections, e.g., upper respiratory tract infections, but have not yet been associated with specific oral conditions. T-cell defects tend to increase susceptibility towards oral infections with fungi and virus, and are also associated with periodontal disease in HIV-infected patients. Defects in the phagocytic system increase the risk of periodontal disease in certain patient groups. Severe granulocytopenia as observed, e.g., in leukemic patients increases the risk of septicemia with oral micro-organisms. PMID- 2202748 TI - Oral infections related to radiation and immunosuppressive therapy. AB - The frequency of oral infection complications after cytotoxic chemotherapy and radiochemotherapy is significant, often contributing to serious septic infectious complications. Generally, the more intense the cytotoxic therapy, the more common are the oral infection complications. In the present review, the spectrum of oral infections related to radiation and immunosuppressive therapy are evaluated and the different local and systemic treatment modalities are presented. PMID- 2202749 TI - Oral complications associated with cancer therapy. An M. D. Anderson Cancer Center experience. AB - Oral complications associated with cancer therapy may not be inevitable. The intensity and duration can be prevented or alleviated by correcting existing oral dental pathology and maintaining meticulous oral care. Microbial (bacterial, fungal and viral) assessment not only allows appropriate documentation of mucositis versus mucosal infection but directs therapeutic treatment. PMID- 2202750 TI - Implants and infections with special reference to oral bacteria. AB - Osseointegration or bony anchorage of oral implants was first described by Branemark and coworkers. This type of connection between the titanium oxide layer and the bone gives stable long-term results for the implants in function. Fibrous tissue interphase between implant and bone will allow mobility which will gradually increase and cause implant failure. The microbiota around stable versus failing implants seem to parallel the patterns around healthy versus diseased natural teeth. Infections most often develop around failing implants. This may create mostly localized, but sometimes even widespread serious infection problems. Metastatic infectious problems related to endo-prosthesis replacing joints and cardiovascular structures are briefly discussed in connection with bacteremia caused by oral infections in general and surgical procedures. PMID- 2202751 TI - The effects of amiodarone on thyroid hormone function: a review of the physiology and clinical manifestations. AB - Amiodarone, an iodinated benzofuran derivative, is used for treatment of refractory cardiac arrhythmias. Certain features of the drug's structure resemble those of the biologically active thyroid hormone, triiodothyronine (T3). In addition, the drug has a variety of complex effects on thyroid hormone physiology, including a number of possible antagonistic effects on thyroid hormone function at the cellular level. The drug occasionally causes clinically overt hyperthyroidism and hypothyroidism. We review these effects and discuss their clinical implications. PMID- 2202752 TI - Co-enzyme Q10: a new drug for cardiovascular disease. AB - Co-enzyme Q10 (ubiquinone) is a naturally occurring substance which has properties potentially beneficial for preventing cellular damage during myocardial ischemia and reperfusion. It plays a role in oxidative phosphorylation and has membrane stabilizing activity. The substance has been used in oral form to treat various cardiovascular disorders including angina pectoris, hypertension, and congestive heart failure. Its clinical importance is now being established in clinical trails worldwide. PMID- 2202753 TI - Intravenous captopril in congestive heart failure. AB - Hemodynamic and neurohumoral effects of intravenous captopril were studied in ten patients with severe chronic congestive heart failure (NYHA Functional Class III and IV). Incremental bolus doses of captopril, titrated to a maximum cumulative dose of 15 mg, were given at 10-minute intervals. Systemic arterial pressure, mean pulmonary capillary wedge pressure, systemic vascular resistance, mean pulmonary artery pressure, and heart rate decreased (P less than .05). Cardiac index and stroke volume index increased (P less than .05). Maximum hemodynamic effects occurred after cumulative doses of 7 mg and were seen within 30 minutes after initiation of therapy; responses persisted for 30-90 minutes after the last dose. Plasma renin activity increased, and plasma atrial natriuretic factor concentration decreased. No adverse effects were observed with the use of intravenous captopril. Thus, intravenous captopril produces rapid and favorable hemodynamic improvement in advanced heart failure patients. PMID- 2202754 TI - Assessment of renal function and damage in animal species. A review of the current approach of the academic, governmental and industrial institutions represented by the Animal Clinical Chemistry Association. AB - There are a wide variety of laboratory tests available to assess damage to and functional impairment of the kidneys, although the effectiveness of these tests varies greatly depending upon the site specificity of the damage and to a lesser extent upon the animal species involved. Several traditional tests of renal dysfunction and damage, including plasma creatinine and urea, and urinalysis (dipstick and/or quantitative protein), can be used in the first instance to detect nephrotoxicity. A second tier of specific, targetted indicators (concentration test, urinary enzymes, clearance of analytes, specific proteins, etc.) may then be applied to identify further the site of the lesion and the functional status of the kidneys. The glomerular filtration rate (GFR) may be estimated from the clearance of exogenous and endogenous substances. The difficulty in obtaining accurately timed urine samples limits the value of these tests in small animals, although methods that do not involve urine collection are available. The kidney is the origin of several enzymes found in urine that can be used to monitor the toxic effects of chemicals and therapeutic substances. Selective measurement of enzyme activities in urine can be used to detect the site of the renal lesion after traditional tests have established the presence of renal injury. Separation of proteins in urine by electrophoretic techniques may also be used to discriminate damage to different parts of the nephron. Renal cell excretion in urine is a sensitive but unreliable indicator of acute damage to the proximal tubule. The rate of cell excretion is not a good predictor of the severity of tubular injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2202755 TI - Toxicology update. PMID- 2202756 TI - Liquid ventilation during early development: theory, physiologic processes and application. AB - Clinical statistics indicate that extrauterine viability becomes increasingly compromised at earlier gestational ages. It is generally accepted that this trend is largely due to the immaturity of the pulmonary system. Investigators have attributed the high degree of instability during the perinatal period of the preterm infant to incomplete biochemical development of the lung. Whereas disruption in biochemical development results in alveolar surfactant deficiency, elevated interfacial tension, alveolar instability, and inadequate pulmonary gas exchange, it is possible that incomplete development of other components within the pulmonary as well as other organ systems may also influence ultimate extrauterine viability of the preterm neonate. However, until recently, little was known in this regard as conventional gas ventilation techniques have been unsuccessful in supporting a stable animal preparation for controlled experimental investigation of physiologic processes before approximately 85% gestation. In the early 1970s, the concept of liquid ventilation was applied to the preterm and newborn animal. Since this time, technological advances in liquid delivery systems have established this experimental approach as a viable means to support the preterm infant during the transition from the liquid-filled intrauterine to gas-filled extrauterine environment. Reduction of surface tension, improvement in lung mechanics, effective pulmonary gas exchange, acid base balance, improved distribution of pulmonary blood flow, and cardiovascular stability in the liquid ventilated preterm animal support the use of this alternative method of ventilation as a valuable experimental tool and potential clinical therapeutic modality during early development. The evolution of this approach is presented in this article. PMID- 2202757 TI - Differences in turnover between thymic medullary dendritic cells and a subset of cortical macrophages. AB - To investigate the turnover of thymic accessory cells, we performed vascular thymus transplantation in RT7 congenic rats. mAb specific for one of the two allelic variants of the RT7 molecule, as well as mAb specific for either medullary interdigitating cells or a subset of cortical macrophages (M phi), were used on cryostat sections and cell suspensions prepared from grafted thymuses to monitor the turnover of these two cell types. In contrast to the complete turnover of interdigitating cells within 3 wk after transplantation, ED2-labeled cortical M phi showed a very slow turnover. Seventy-six days after transplantation, more than 30% of these M phi were found to be still of donor origin. The different turnover rates of these thymic accessory cells could reflect their function in T cell development. PMID- 2202758 TI - An analysis of insulin receptor expression and binding on MHC class I positive and negative human lymphoblastoid cells. AB - Recent studies have demonstrated a specific membrane association between the polymorphic class I antigens of the MHC and the insulin receptor (IR). In some reports, variation in IR binding is attributed to the class I phenotype. To extend these observations, we have examined whether MHC class I products influence IR function, in particular, high affinity ligand-specific binding. Using two independent methods, we have compared IR affinity and density on a human B-lymphoblastoid cell line expressing HLA-A, -B products vs a null mutant and a set of transfectants where HLA-A3, -B7, or -Bw58 expression has been restored through gene transfer. The results from radioreceptor assay and RIA measuring IR binding and expression indicate that although there is a decrease in high affinity insulin binding sites in the HLA-A, -B null mutant, ligand binding cannot be restored in the transfectants expressing HLA-A or -B alleles. We conclude that the MHC class I products do not determine the insulin-binding phenotype of the cells examined in this study. Alternatively, we propose that insulin receptor heterogeneity in affinity and density may be influenced by other undetermined factors inherent to clonally expanded cells, thereby complicating dissection of IR/MHC interactions. PMID- 2202759 TI - Effects of stress on lysability of tumor targets by cytotoxic T cells and tumor necrosis factor. AB - The effects of stress on four tumor cell lines are analyzed in view of the possibility that stress protects tumor cells against immune attack. We show that stress causes resistance to CTL and TNF in two cell lines. Induction of resistance is time dependent and reversible and not due to failure of killer cells to interact with stressed targets. It is shown that stress induces stress proteins concomitant with induction of resistance to killer cells and TNF. Moreover experiments are presented suggesting that resistance to either immune effector is due to independent mechanisms. The conclusion that stress can induce mechanisms in targets that interfere with the action of TNF as well as with target lysis following a lethal hit by CTL is discussed. PMID- 2202761 TI - Evaluation of dissociation constants of antigen-antibody complexes by ELISA. AB - In this communication some of the advantages and constraints in the use of ELISA (enzyme-linked immunosorbent assay) procedures to evaluate antigen-antibody dissociation constants (Kd) are discussed and experimental conditions under which the effective Kd is close to the true value are proposed. Interactions between horseradish peroxidase (POD), human myoglobin and insulin with mono- and polyclonal antibodies (McAb and PcAb) were used to demonstrate that ELISA can be used to determine the average Kd, characterizing the interaction between antigens and PcAb. The Kd values obtained by ELISA were similar to those determined by luminescent immuno-cofactor analysis (LICA). PMID- 2202760 TI - Analysis of leukocyte surface antigens on ethanol-fixed paraffin-embedded tissue material. AB - Ethanol-fixed paraffin-embedded specimens of human tissues were studied whether the surface antigens of leukocytes in these tissues can be stained and analyzed. Three-layer indirect immunoperoxidase staining was performed on the ethanol-fixed paraffin-embedded sections by the use of several monoclonal antibodies for whole human leukocytes (Dako LC), B cells (Dako CD-22, 4KB5, and L26; Leu 14), T cells and their subsets (Dako UCHL-1, T1, T3, T4 and T8; Leu 4, 3a and 2a) and monocyte/macrophage lineage (Dako macrophage, Leu M1, M3 and M5). The results were compared with those on fresh-frozen sections. No essential differences were obtained between the paraffin-embedded and the fresh frozen sections stained by the following antibodies; Dako LC for whole human leukocytes; Dako UCHL-1, T3 and Leu 4 for T cells; Dako CD22, 4KB5, L26 and Leu 14 for B cells; Dako macrophage, Leu M1 and M5 for monocyte/macrophage lineage. On the other hand, the subsets of T cells could only be detected on the fresh-frozen sections. The results of the leukocyte analysis on the paraffin-embedded specimens of several renal diseases were very similar to those reported by other investigators on fresh-frozen sections or PLP-fixed materials. Thus, by the use of appropriate monoclonal antibodies, the ethanol-fixed paraffin-embedded material can be used for leukocyte analysis except for the definition of T cell subsets. PMID- 2202762 TI - Integration of monoclonal antibodies in quantitative immunoelectrophoresis by indirect immunoprecipitation. AB - Characterization of the specificity of monoclonal antibody in crossed immunoelectrophoresis has been achieved by mixing the monoclonal antibody with mycobacterial antigen in the circular antigen well. After electrophoresis in the first dimension, the separated antigens and antigen complexed with monoclonal antibody were run into an intermediate gel containing rabbit anti-mouse immunoglobulin and a top gel with polyvalent rabbit anti-BCG immunoglobulin. Monoclonal antibody with bound antigen precipitated in the intermediate gel while the other antigens precipitated in their reference positions. The method was simple, efficient and sensitive. Selected monoclonal antibodies were used to demonstrate the characteristic features of the method. In rocket immunoelectrophoresis the rocket height of a monoclonal antibody may be significantly altered by adding the relevant antigen. This principle can be exploited when the polyvalent antibodies do not precipitate the antigen, and it may be used for efficient screening of monoclonal hybridoma culture supernatants. This approach may permit the quantitation of an antigen when only monoclonal antibody is available. PMID- 2202763 TI - The use of E. coli exonuclease III to generate single stranded DNA in BrdUrd cell cycle analysis permits simultaneous detection of cell surface antigens. AB - An immunocytochemical method for the simultaneous flow cytometric quantitation of total cellular DNA, incorporated 5-bromo-2'-deoxyuridine (BrdUrd) and one or more cell surface antigens has been developed. Biotin labeling of cell surface antigens, critically tuned fixation techniques and an enzymatic denaturation of cellular DNA are the essential features of this method. Enzymatic denaturation of cellular DNA was shown to prevent loss of cell surface antigen-bound biotin moieties, and thus to preserve cell surface immunofluorescence distribution. After a mild protein extraction and the introduction of breaks into the chromatin using restriction endonucleases, E. coli exonuclease III was used to generate stretches of single stranded DNA. This approach permits detection of the incorporated BrdUrd using anti-BrdUrd monoclonal antibodies. The enzymatic denaturation protocol was optimized using in vitro BrdUrd-labeled L1210 murine leukemia cells, and applied to both in vivo and ex vivo BrdUrd-labeled murine bone marrow cells. With this new method it is possible to study DNA content, cell cycle kinetics and cell surface antigen expression simultaneously, and hence functional relationships between these parameters can be investigated. PMID- 2202764 TI - Isolation and flow cytometric analysis of the free lymphomyeloid cells present in murine liver. AB - Recruitment of circulating lymphomyeloid cells in the liver during infection often plays a critical role, mediating control or exacerbation of the pathogen growth. This paper describes a simple and rapid technique to recover these lymphomyeloid cells from a normal or an infected liver. After portal perfusion with saline buffer, the liver is gently dissociated on steel screens and the resulting cell population spun in 35% Percoll in 100 IU/ml Calciparine to remove all nuclei and cell debris: the recovery of a pure liver lymphomyeloid cell population is usually achieved in 40-60 min. Phenotypic and functional analysis could then be easily carried out on this cell population. This methodology was applied to normal mouse liver: flow cytometric analysis of the purified free lymphomyeloid cells showed the presence of T lymphocytes (46% +/- 3 with a CD4/CD8 ratio of 2.8), B lymphocytes (20% +/- 2 IgG and 30% IgM positive) and myelomonocytic cells (14% +/- 2 complement receptor type III positive). PMID- 2202766 TI - A novel enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to HIV-1 envelope glycoproteins based on immobilization of viral glycoproteins in microtiter wells coated with concanavalin A. AB - We have developed a novel method that greatly simplifies the preparation of solid phase HIV-1 envelope glycoproteins for use in an ELISA that detects serum antibodies to HIV envelope antigens. This method utilizes concanavalin A absorbed to wells of microtiter plates to affinity immobilize detergent-solubilized viral glycoproteins released in culture fluids of HIV-1 infected cell lines grown in serum free medium. Antibodies binding to ConA-immobilized viral antigens are detected by peroxidase-conjugated antibodies and appropriate enzyme substrates. Unlike most commercial HIV ELISAs, which utilize gp120 depleted-purified virus as the source of antigens and thus favor detection of antibodies to core antigens, the ConA envELISA is highly sensitive for detecting antibodies to native gp120, as evidenced by the strong reactivity of gp120-specific human monoclonal antibodies. Our results also suggest that representation of gp41 in the assay varies and depends on which virus infected cell lines are used for antigen production. Since this assay accurately identified 14 HIV-1 antibody positive patient sera and no false positives were detected among 16 HIV-1 negative sera, the ConA envELISA shows promise as an inexpensive assay for the serologic diagnosis of HIV infections. PMID- 2202765 TI - Enumeration of IgE secreting B cells. A filter spot-ELISA. AB - To assess the frequency of IgE producing cells in humans a filter immunoplaque assay has been developed to detect IgE secretion from individual B lymphocytes in unfractionated peripheral blood mononuclear cells (PBMC). PBMC were incubated in microfilter plates containing nitrocellulose membranes coated with polyclonal anti-human IgE antibody, and the IgE production by a single cell was detected using a specific anti-human IgE monoclonal antibody followed by enzymatic development. The products of the enzymatic reaction were visualized as blue plaques on the membranes. The assay was both sensitive and specific as determined by: (1) a near 1:1 correlation between direct cell counts of an IgE producing myeloma cell line (U266) and the number of plaques in the filter immunoassay; and (2) the absence of detectable plaques generated by human B cells transformed by Epstein-Barr Virus (EBV) and producing only IgG or IgM. The presence of other cell types in PBMC did not affect the ability to detect IgE secreting cells. Replicate cultures of highly purified B lymphocytes, first transformed with EBV and then stimulated with recombinant human interleukin-4, produced IgE levels in culture supernatants that correlated closely with the number of IgE producing cells (r = 0.93; P less than 0.001). Furthermore, using the same transformed cells, the number of IgE secreting cells assessed by the immunoplaque assay was significantly correlated (r = 0.94; P = 0.002) with the number of IgE producing cells assessed by immunofluorescence staining of intracytoplasmic IgE. This assay provides a simple and direct method to assess the frequency of IgE producing lymphocytes in humans. PMID- 2202767 TI - Carbohydrate-enzyme conjugates for competitive EIA. AB - Enzyme glycoconjugates prepared from oligosaccharides or polysaccharides are efficient and durable reagents for direct, competitive enzyme immunoassays based on solid phase antibody. This assay format facilitates simple measurement of association constants and relative inhibitory power of oligosaccharides, while also providing a sensitive quantitative assay of bacterial polysaccharide antigens. Enzyme-saccharide conjugates were prepared by established glycoconjugate methodologies, and protocols for their optimal use were established by investigating the effects of solid phase antibody concentration on the kinetic equilibrium of binding for different antigen-enzyme conjugate concentrations, in the presence and absence of inhibitor. Four discrete monoclonal antibody-carbohydrate antigen systems were studied and it is demonstrated for each, that the relative inhibitory power of oligosaccharides may be readily measured in a convenient assay format, and that association constants can be extrapolated from the same assay data. PMID- 2202768 TI - [Study on carbohydrate antigen NCC-ST-439 in breast cancer]. AB - We evaluated the clinical significance of serum NCC-ST-439 (ST439) in sera from 20 healthy women, 8 patients with benign breast disease and 105 patients with breast cancer (79 primary, 26 recurrent) by using enzyme immuno-assay (EIA). No false positive case was noted in the measuring of ST439 for healthy women and patients with benign breast disease. The positive rates of ST439 were 23% (18/79) in primary breast cancers and 50% (13/26) in recurrent breast cancers. The serum levels of ST439 in stage I breast cancer was significantly higher (p less than 0.05) than those in healthy women, but there was no significant difference among each stage. The serum levels of ST439 were not significantly different among the subsets such as T, n, m and histological types. The high levels of serum ST439 were observed in two cases with mucinous carcinoma. Although there were no relation between ST439 and receptor status, the higher serum levels of ST439 were observed in postmenopausal patients than premenopausal ones. The positive frequency of serum ST439 in stage I and II breast cancers was higher than that of CEA, TPA or CA15-3, while the positive rate in recurrent breast cancer was the lowest among 4 tumor markers. These results suggest that ST439 is a useful tumor marker for not only detecting the recurrence of breast cancer but also diagnosing primary breast cancer in early stage. PMID- 2202769 TI - [A clinicopathological analysis of renal cell carcinoma in solitary kidney]. AB - Seven patients with renal cell carcinoma, who had undergone uninephrectomy or who had only one functioning kidney were clinicopathologically studied. They were 5 males and 2 females, with ages ranging from 51 to 74 years (mean: 61 years). Of these cases, 4 had undergone uninephrectomy for renal cell carcinoma, and 1 had received uninephrectomy because of renal calculus. In the remaining 2 cases, one kidney did not function (hypoplastic kidney). Renal cell carcinoma was discovered by macroscopic hematuria in 2 cases, during the follow-up observation after a previous surgical treatment of renal cell carcinoma in 4 cases and by abdominal computed tomography during treatment of abdominal aneurysm in 1 case. Excluding one case with multiple metastases, all cases were surgically treated (3 with partial nephrectomy and 3 with enucleation). During surgery, renal blood vessels were clamped for 24-60 minutes (mean: 38 minutes). After operation, 5 cases showed an elevation in serum creatinine (greater than or equal to 2.0 mg/ml), which, however, was normalized rapidly by conservative treatment. They have been followed up for 6 months to 7 years and 8 months after operation (mean: 2 years and 11 months). The case which had undergone before and recently received enucleation (2 pieces) showed metastasis of cancer to the pancreas 2.5 years after the recent operation. Therefore, this case additionally received partial pancreatectomy. The results of this study suggest that conservative surgical treatments are appropriate for the treatment of renal cell carcinoma in patients with solitary kidney from viewpoint of the quality of life, so long as postoperative management is sufficiently made. PMID- 2202770 TI - [A double blind study to evaluate the optimal dose and its frequency for oral administration of OK-432 (picibanil) by immunological parameters (the 2nd report)]. AB - The present study was designed to determine the optimal dose and frequency of oral administration of a biological response modifier, OK-432 (Picibanil), which has been used for cancer immunotherapy by injection. Ninety one stomach cancer patients were randomly assigned into 7 groups and were administered a placebo or OK-432 at a dose of 5, 20 or 40KE, once or 3 times a week before operation (5KE X 1/W, 20KE X 1/W, 40KE X 1/W, or X 3/W). Misregistration excluded 3 patients and the data of 88 patients were analysed. There was no significant difference in the background status of the patients in each group. In the 1st report, we already showed that 5KE X 3/W might be the optimal regimen to augment the natural killer (NK) activity of regional lymph node lymphocyte (RNL). In the 2nd report, we searched for the optimal regimen to augment the antitumor immunity of T lymphocytes. The proliferative response of RNL to SuPR (protein derived from OK 432) was augmented in all the groups administered OK-432. The responsiveness of PBL to autologous tumor extract enhanced by IL-2 was augmented by 5KE X 1/W, and that of RNL was augmented by 5KE X 3/W. The killer/suppressor (Leu2+15-/Leu2+15+) ratio in RNL increased in all the groups administered OK-432 especially in 20KE X 3/W group. Oral administration of OK-432 augmented both non-specific and the specific antitumor immunity of PBL as well as RNL, and 5KE X 3/W may be the optimal regimen to augment the antitumor immunity, especially of RNL. PMID- 2202771 TI - Transient expression of virus-specific promoters in murine resident peritoneal macrophages. AB - Monocyte-macrophages (MO), being non-permissive for most viruses, play an important role in resistance to virus infection. In order to establish the mechanism of abortive infection of murine resident peritoneal MO (ResPMO) by herpes simplex virus type 1 (HSV-1), it is desirable to transfect these cells with viral promoters linked to an assayable gene, for example, the bacterial chloramphenicol acetyl transferase (CAT) gene. This will facilitate studies designed to measure levels of promoter activation or repression in these specialized cells. Transient expression of CAT in ResPMO was achieved with DEAE dextran, but not using either calcium phosphate precipitate or lipofectin. CAT expression driven by various virus-specific promoters was less efficient in ResPMO compared with Vero cells and approximately 50% of input plasmid DNA remained in Vero cells at 48 h post transfection, but only 9% was detectable in ResPMO. However, approximately 6% of ResPMO and 9% of Vero cells contained CAT specific DNA at 24 h post transfection. In addition, 2% of cells of either cell type contained CAT-specific polypeptide at 48 h. This is therefore the first report that the non-replicating murine ResPMO can be transfected in vitro and more importantly, that these cells express the transfected gene products. PMID- 2202772 TI - Production of collagen type I by mouse peritoneal macrophages. AB - The origin and identity of the cells that accumulate and produce collagen in wound healing and in granulomatous and fibrotic processes have long remained unsettled. In this study, it was found that pure cultures of peritoneal macrophages produced hydroxy-L-proline not associated with Clq and produced detectable quantities of collagenase-digestible protein. Cultured macrophages synthesized collagen while retaining their phagocytic capacity. Immuno-blot analysis identified the collagen as Type I. This shows that macrophages have collagen-forming capacity and may be productive cells in pathologic collagen deposition. PMID- 2202774 TI - Validity testing of commercial urine cocaine metabolite assays: IV. Evaluation of the EMIT d.a.u. cocaine metabolite assay in a quantitative mode for detection of cocaine metabolite. AB - The EMIT d.a.u. cocaine metabolite assay (EMIT dau) was evaluated in a quantitative mode for analysis of clinical specimens obtained after controlled cocaine administration to human subjects. The quantitative results showed high concordance with those of gas chromatography/mass spectrometry (GC/MS) assays of the same specimens for benzoylecgonine, and no false positive or false negative results were obtained. The evaluation also included analysis of standardized solutions containing benzoylecgonine, cocaine, and other cocaine metabolites and isomers. The EMIT dau antibody demonstrated high selectivity for benzoylecgonine. The precision was somewhat less than that reported earlier for other commercial cocaine metabolite immunoassays. Quantitation of initial screening results from EMIT dau testing can serve as a useful guide for confirmation by GC/MS in forensic science urine testing. PMID- 2202773 TI - Prospective comparison of patient tolerance to enteric-coated vs nonenteric coated erythromycin. AB - Erythromycin base and its salts are frequently used in clinical practice. The most frequent side effects of oral erythromycin preparations are gastrointestinal. Various salts and enteric coatings have been developed without adequate comparison in regard to gastrointestinal side effects. The overall incidence of gastrointestinal side effects (abdominal pain and cramps, nausea, vomiting, diarrhea, and gas) of two common erythromycin base formulations, Erythromycin Base Filmtab (Abbott), a nonenteric-coated base tablet, and Eryc (Parke-Davis), a pelletized, encapsulated, enteric-coated base capsule, were compared in 368 adults at two dosage levels (1 g/d and 2 g/d). Minimal differences were found when target symptoms were compared by preparation coating. In contrast, subjects receiving erythromycin at the 2-g/d dosage level reported higher incidence rates for each of the target symptoms, regardless of product coating, than did those patients treated at the 1-g/d dosage level. Enteric coating of erythromycin base offers little protection from the common dose related gastrointestinal adverse effects of oral erythromycin. PMID- 2202775 TI - Pete Maravich's incredible heart. AB - Postmortem examination of a former professional basketball player revealed an abnormal heart, most notably a single coronary artery. The literature on single coronary arteries is briefly reviewed, and the possible mechanism which caused the patient's condition is considered. This case is particularly unusual because of the patient's profession, which is so physically demanding. PMID- 2202776 TI - Pathogenicity and the microbe in vivo. The 1989 Fred Griffith Review Lecture. PMID- 2202777 TI - Energetics of Saccharomyces cerevisiae in anaerobic glucose-limited chemostat cultures. AB - The energetics of Saccharomyces cerevisiae were studied in anaerobic glucose limited chemostat cultures via an analysis of biomass and metabolite production. The observed YATP was dependent on the composition of the biomass, the production of acetate, the extracellular pH, and the provision of an adequate amount of fatty acid in the medium. Under optimal growth conditions, the YATP was approximately 16 g biomass (mol ATP formed)-1. This is much higher than previously reported for batch cultures. Addition of acetic acid or propionic acid lowered the YATP. A linear correlation was found between the energy required to compensate for import of protons and the amount of acid added. This energy requirement may be regarded as a maintenance energy, since it was independent of the dilution rate at a given acid concentration. PMID- 2202778 TI - Changes in the incorporation of carbon derived from glucose into cellular pools during the cell cycle of Saccharomyces cerevisiae. AB - The rate of incorporation of 14C derived from [U-14C]glucose into cells of Saccharomyces cerevisiae X2180(1B) was investigated as a function of the cell cycle. After pulse-labelling of exponentially growing populations, centrifugal elutriation was used to isolate various cell fractions of increasing cell size, representing successive stages of the cell cycle. The total amount of 14C incorporated per cell was found to increase continuously during the cell cycle along with cellular protein content and Coulter counter cell volume. This pattern supports the model of exponential cell growth. In order to evaluate changes in intracellular carbon flow during the cell cycle, chemical extraction procedures were used to obtain four cellular fractions enriched in either low-molecular-mass components, lipid material, polysaccharides or proteins. The distribution of 14C among these cellular fractions varied during successive stages of the cell cycle, indicating cell-cycle-dependent fluctuations in intracellular carbon flow. During the G1 phase the flow of 14C into the low-molecular-mass pool increased markedly; concurrently, the rate of incorporation into the polysaccharide-enriched pool decreased. PMID- 2202779 TI - Localization of dipeptidyl aminopeptidase yscIV in the plasma membrane of Saccharomyces cerevisiae. AB - The subcellular distribution of dipeptidyl aminopeptidase activity was studied in protoplast lysates of Saccharomyces cerevisiae that were virtually free from vacuolar contamination. Dipeptidyl aminopeptidase yscIV, the STE13 gene product, was found to be associated with plasma membrane vesicles after sucrose gradient isopycnic centrifugation. Another dipeptidyl aminopeptidase activity, not yet fully characterized, was localized in a microvesicular population co-sedimenting with chitosomes. PMID- 2202780 TI - Characterization of enterobacteria by esterase specific-activity profiles. AB - The spectrum of specific activities and the electrophoretic mobilities of esterases produced by 550 strains of Enterobacteriaceae belonging to 36 species and subclassified into six groups (group 1, Escherichia coli, Shigella and Escherichia hermanii; group 2, genus Salmonella and genus Citrobacter; group 3, genus Klebsiella and genus Enterobacter; group 4, genus Serratia and Serratia fonticola; group 5, genus Proteus, genus Providencia and genus Morganella; and group 6, genus Yersinia) were analysed by acrylamide/agarose gel electrophoresis using standardized methods for staining and mobility comparisons. Nineteen types of esterase were defined by their respective esterase specific-activity profile (ESAP). A multiple correspondence analysis (MCA) of the ESAP data enabled 82% of the strains in the 36 species to be correctly classified. In each group, the species were clearly delineated after MCA on both ESAP and electrophoretic mobility data. In addition, the smallest number of characters providing species identification of Yersinia strains by esterase polymorphism was identified by means of a binary segmentation tree technique. PMID- 2202781 TI - Biological properties of lipopolysaccharides from Bordetella species. AB - Biological activities of lipopolysaccharides (LPS) extracted from Bordetella pertussis, B. parapertussis and B. bronchiseptica were compared with those of Escherichia coli LPS. The LPS preparations from B. pertussis showed biological activities comparable to those of E. coli LPS in terms of lethal toxicity in galactosamine-sensitized mice, pyrogenicity in rabbits, mitogenicity in C3H/He spleen cell cultures, macrophage activation, and induction of tumour necrosis factor. All the activities of LPS preparations from B. parapertussis, except mitogenicity, were lower than those of E. coli LPS. LPS from B. parapertussis gave the greatest mitogenic action of all those tested. Biological activities stronger than or comparable to those of E. coli LPS were observed for LPS from B. bronchiseptica. PMID- 2202782 TI - Cloning and sequencing the messenger RNA of the N gene of viral haemorrhagic septicaemia virus. AB - The mRNA transcribed from the N gene of viral haemorrhagic septicaemia virus (VHSV) of salmonids has been cloned in Escherichia coli and expressed. Fusion proteins were recognized by monoclonal antibody directed against the N protein from the viral particle. A 1212 bp long open reading frame (ORF) coding for 404 amino acids with a calculated Mr of 44590 was deduced from the nucleotide sequence. The ORF was preceded by a 93 bp segment including in position 42 the AACAC pentanucleotide which is presumed to be the start signal for transcription by analogy with other rhabdoviral mRNAs. The upstream 41 bp region could correspond to the covalently linked positive polarity leader RNA as also found on the N mRNA from infectious haematopoietic necrosis virus (IHNV). This may be a characteristic of fish lyssaviruses. The AAACC sequence, which is part of the leader, was not found. Amino acids 44 to 359 from IHNV and 45 to 360 from VHSV are 45.3% homologous. A strong homology which could reflect functional importance was also found for potential phosphorylation sites and hydrophobic peaks despite the fact that the two viruses evolved on different continents. PMID- 2202783 TI - Molecular cloning and physical mapping of the genome of Bombyx mori nuclear polyhedrosis virus. AB - A restriction fragment library which covered the entire genome of Bombyx mori nuclear polyhedrosis virus (BmNPV) was constructed using plasmid vectors. By analysis of cloned and viral DNA by double digestion with endonucleases and by hybridization techniques, a complete physical map of BmNPV was constructed for BamHI, EcoRI, HindIII, KpnI, PstI and SmaI. Five regions of repeated sequences containing EcoRI sites were also found and mapped. PMID- 2202784 TI - Detection of respiratory syncytial virus antigen after seventy-two hours of culture. AB - Between September, 1987, and April, 1989, three techniques for the detection of respiratory syncytial virus (RSV) were compared: indirect immunofluorescence (IF) on the sample, indirect immunofluorescence after 72 h of MRC-5 cell culture (IF 72h), and detection of the cytopathic effect (CPE) by MRC-5 and HEp-2 cell culture. A study of 383 nasal aspirates from young children admitted to the Centre Hospitalier de Nantes (CHR) showing miscellaneous respiratory symptoms produced the following results: 143 samples (37%) were RSV positive by IF, 119 (31%) were positive by IF 72h, and 117 (31%) showed RSV-induced CPE. In comparison with tissue culture isolation (TC), the sensitivities of IF and IF 72h were 89% and 80% and their specificities 85% and 91%, respectively. During the winter of 1988-1989, of the 110 RSV-positive nasal aspirates (104 by IF, 89 by IF 72h, 83 by CPE detection), 109 were identified by IF and/or IF 72h. IF 72h affords rapid detection of RSV. PMID- 2202786 TI - Silver accumulation and resistance in Escherichia coli R1. AB - E. coli R1 contains at least 2 large plasmids (83 and 77 kb) while E. coli S1 was previously cured of the 83 kb plasmid. Transformation using artificial competence, high-voltage electroporation, and plasmid mobilization experiments with the mobilizing plasmid RP4, failed to ascertain the 83 kb plasmid was responsible for Ag(+)-resistance. Silver accumulation by an Ag(+)-sensitive E. coli S1 strain was 5-fold higher than an Ag(+)-resistant E. coli R1 strain. The Ag(+)-resistant E. coli R1 strain produced 33% more H2S and 32% more intracellular acid labile SH than the Ag(+)-sensitive E. coli R1 strain when grown in the absence of AgNO3. Hydrophobic interaction chromatography revealed E. coli R1 displayed higher cell surface hydrophobicity than E. coli S1. HPLC protein analysis of cell-free extracts also revealed differences between protein fractions in E. coli R1 and S1 strains. PMID- 2202785 TI - Disturbance of the 5-hydroxytryptamine metabolism in brains from patients with Alzheimer's dementia. AB - The 5-hydroxytryptamine (5-HT) system in the human brain is sensitive to aging. In dementia of the Alzheimer type (AD/SDAT), there are significantly reduced concentrations of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA). 5-HT-sensitive imipramine binding is reduced by almost 50%, indicating a loss of presynaptic 5 HT terminals. There also seems to be reduced tryptophan hydroxylase activity in some brain areas. In cerebrospinal fluid (CSF) from AD/SDAT patients, the concentration of 5-HIAA is reduced, and the accumulation of 5-HIAA after probenecid loading is diminished. Biochemical findings together with structural findings in the raphe nuclei indicate that the disturbance of the 5-HT system is of the same magnitude as the disturbance of the cholinergic system. Reduced activity in the 5-HT system may be of importance for activity in the hypothalamus. There is an increased concentration of arginine vasopressin, which may explain the increased activity in the hypothalamic-pituitary-adrenal axis seen in patients with AD/SDAT. This activity is reduced when a selective 5-HT reuptake blocker is given. Pharmacological treatment with 5-HT reuptake blockers improves emotional disturbances, confusion, anxiety and depressed mood in patients with AD/SDAT. PMID- 2202787 TI - Cure of a man with solitary abscess of the brain-stem. PMID- 2202788 TI - Prognostic significance of peritumoral lymphatic and blood vessel invasion in node-negative carcinoma of the breast. AB - The prognostic significance of intramammary lymphatic and blood vessel invasion was evaluated in a retrospective series of 221 patients with node-negative carcinoma of the breast treated with modified radical mastectomy. To facilitate identification of lymphatic and blood vessel invasion, the tumors were studied with an immunohistochemical technique using antibodies to endothelial markers. Peritumoral lymphatic and blood vessel invasion (PLBI) (encompassing both lymphatic and blood vessel invasion) was an adverse prognostic indicator independent of menopausal status, tumor size, and other histologic variables. Recurrence of disease and death resulting from carcinoma were significantly higher for patients with PLBI-present (+) tumors compared with patients with PLBI absent (-) tumors (P less than .0001). The risk of recurrence for patients with PLBI+ tumors was 4.7 times that for their PLBI- counterparts. The presence of intratumoral lymphatic and blood vessel invasion (ILBI) is less important because few examples were found without concomitant PLBI. When PLBI was separated into lymphatic invasion and blood vessel invasion individually, the prognostic significance was retained in both groups. The immunohistochemical approach reduced both false-negative and false-positive observations and identified about 40% of PLBI that would have been missed by routine histologic examination alone. The presence of PLBI appears to be a potentially useful discriminant in predicting the outcome of patients with node-negative carcinoma of the breast. PMID- 2202789 TI - Adjuvant therapy of Dukes' A, B, and C adenocarcinoma of the colon with portal vein fluorouracil hepatic infusion: preliminary results of National Surgical Adjuvant Breast and Bowel Project Protocol C-02. AB - Between March 1984 and July 1988, 1,158 patients with Dukes' A, B, and C carcinoma of the colon were entered into National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol C-02. Patients were randomized to either no further treatment following curative resection or to postoperative fluorouracil (5-FU) and heparin administered via the portal vein. Therapy began on day of operation and consisted of constant infusion for 7 successive day. Average time on study was 41.8 months. A comparison between the two groups of patients indicated both an improvement in disease-free survival (74% v 64% at 4 years, overall P = .02) and a survival advantage (81% v 73% at 4 years, overall P = .07) in favor of the chemotherapy-treated group. When compared with the treated group, patients who received no further treatment had 1.26 times the risk of developing a treatment failure and 1.25 times the likelihood of dying after 4 years. Particularly significant was the failure to demonstrate an advantage from 5-FU in decreasing the incidence of hepatic metastases. The liver was the first site of treatment failure in 32.9% of 82 patients with documented recurrences in the control group and in 46.3% of 67 patients who received additional treatment. Therapy is administered via a regional route to affect the incidence of recurrence within the perfused anatomic boundary. Since, in this study, adjuvant portal-vein 5-FU infusion failed to reduce the incidence of hepatic metastases, it may be concluded that its use thus far is not justified. It may also be speculated that the disease-free survival and survival advantages (the latter of borderline significance) are a result of the systemic effects of 5-FU. PMID- 2202790 TI - Effect of patients' expectations of benefit with standard breast cancer adjuvant chemotherapy on participation in a randomized clinical trial: a clinical vignette study. AB - Patients frequently overestimate the benefit of standard breast cancer adjuvant therapy. This is due in part to vague doctor-patient communication. To examine how the doctor's description and patient's expectations of the benefit of standard therapy affect clinical trial participation, we randomized 282 female cancer patients to one of two versions of a clinical vignette describing a choice between standard cyclophosphamide, methotrexate, and fluorouracil (5FU) (CMF) and a randomized trial comparing CMF with cyclophosphamide, doxorubicin, and 5FU (CAF). The vignettes differed only on whether results with CMF were described verbally or numerically in terms of disease-free survival (DFS). After selecting CMF or the trial, patients estimated their 10-year DFS with CMF. Patients were randomized 3:1 to the verbal vignette. The trial was selected by 110 of 210 (52.4%) verbal vignette patients versus 25 of 72 (34.7%) numeric vignette patients (P = .01). Estimates of 10-year DFS with CMF varied considerably; many were inaccurate. When patients in the verbal vignette group were divided into thirds according to DFS estimate, 22 of 64 (34.4%) in the top third selected the trial versus 38 of 64 (59.4%) and 38 of 65 (58.5%) in the middle and bottom third, respectively (P = .005). Younger age, college education, and previous participation in a trial also predicted trial selection. Multivariate logistic regression suggested that the benefit expected from CMF was more important than how benefit was described in treatment selection. Assuring realistic patient expectations of standard adjuvant therapy benefit is likely to be important during discussion of clinical trials. PMID- 2202791 TI - Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B 15. AB - The National Surgical Adjuvant Breast and Bowel Project (NSABP) implemented protocol B-15 to compare 2 months of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) and cyclophosphamide (AC) with 6 months of conventional cyclophosphamide, methotrexate, and fluorouracil (CMF) in patients with breast cancer nonresponsive to tamoxifen (TAM, T). A second aim was to determine whether AC followed in 6 months by intravenous (IV) CMF was more effective than AC without reinduction therapy. Through 3 years of follow-up, findings from 2,194 patients indicate no significant difference in disease-free survival (DFS, P = .5), distant disease-free survival (DDFS, P = .5) or survival (S, P = .8) among the three groups. Since the outcome from AC and CMF was almost identical, the issue arises concerning which regimen is more appropriate for the treatment of breast cancer patients. AC seems preferable since, following total mastectomy, AC was completed on day 63 versus day 154 for conventional CMF; patients visited health professionals three times as often for conventional CMF as for AC; women on AC received therapy on each of 4 days versus on each of 84 days for conventional CMF; and nausea-control medication was given for about 84 days to conventional CMF patients versus for about 12 days to patients on AC. The difference in the amount of alopecia between the two treatment groups was less than anticipated. While alopecia was almost universally observed following AC therapy, 71% of the CMF patients also had hair loss and, in 41%, the loss was greater than 50%. This study and NSABP B-16, which evaluates the worth of AC therapy in TAM-responsive patients, indicate the merit of 2 months of AC therapy for all positive-node breast cancer patients. PMID- 2202792 TI - Prevention of bacteremia attributed to luminal colonization of tunneled central venous catheters with vancomycin-susceptible organisms. AB - Forty-five children with oncologic or hematologic disorders requiring tunneled central venous catheters (TCVC) for the administration of immunosuppressive therapy were randomized to receive either 10 U/mL heparin (H) (24 patients) or a solution of 10 U/mL H and 25 micrograms/mL vancomycin (H-V) (21 patients) for all catheter flushes. Episodes of fever or suspected sepsis were evaluated to determine whether the addition of vancomycin to the flush solution would alter the incidence of symptomatic bacteremia attributed to luminal colonization of TCVC with vancomycin-susceptible bacteria. Patients were enrolled for 247 +/- 150 days, accounting for a total of 11,095 days of catheter use. Bacteremia attributed to luminal colonization with vancomycin-susceptible organisms occurred in five patients (six infections) receiving H alone compared with zero patients receiving H-V (P = .035). The time to the first episode of bacteremia with vancomycin-susceptible organisms, analyzed by Kaplan-Meier survival curves, was significantly longer in patients receiving H-V (P = .04). There were no differences in the incidence of other infections including bacteremia attributed to luminal colonization with vancomycin-resistant organisms, other bacteremias (including those arising from the catheter exit site), exit-site cellulitis, or fungal infections. No organisms resistant to vancomycin were identified. Vancomycin could not be detected in the peripheral blood of patients receiving vancomycin in the flush solution. No vancomycin-related toxicities were noted. We conclude that the use of an H-V flush solution in immunocompromised patients with TCVC can decrease the frequency of bacteremia attributed to luminal colonization with vancomycin-susceptible bacteria. PMID- 2202793 TI - Synaptic connections of neurones identified by Golgi impregnation: characterization by immunocytochemical, enzyme histochemical, and degeneration methods. AB - For more than a century the Golgi method has been providing structural information about the organization of neuronal networks. Recent developments allow the extension of the method to the electron microscopic analysis of the afferent and efferent synaptic connections of identified, Golgi-impregnated neurones. The introduction of degeneration, autoradiographic, enzyme histochemical, and immunocytochemical methods for the characterization of Golgi impregnated neurones and their pre- and postsynaptic partners makes it possible to establish the origin and also the chemical composition of pre- and postsynaptic elements. Furthermore, for a direct correlation of structure and function the synaptic interconnections between physiologically characterized, intracellularly HRP-filled neurones and Golgi-impregnated cells can be studied. It is thought that most of the neuronal communication takes place at the synaptic junction. In the enterprise of unravelling the circuits underlying the synaptic interactions, the Golgi technique continues to be a powerful tool of analysis. PMID- 2202794 TI - Synaptic circuitry identified by intracellular labeling with horseradish peroxidase. AB - During the past two decades new techniques have been developed to directly test the dogma that neuronal structure is correlated with neuronal function. In the earliest experiments, Procion yellow was injected into neurons after they had been characterized physiologically; these neurons were then viewed through the light microscope. Recent advances in the method generally employ horseradish peroxidase as the dye which is injected since it diffuses quite readily throughout the injected neuron and produces a stable reaction product for both light and electron microscopic studies. This review explores the utility of examining synaptic circuitry after physiologically recording from axons or neurons and then injecting horseradish peroxidase into them. As a model system, we studied the cat lateral geniculate nucleus and investigated, at the electron microscopic level, the synaptic contribution to this nucleus from retinogeniculate axons, from interneurons, and from the axon collaterals of neurons that project to visual cortex. PMID- 2202795 TI - Modified dot assay with increased sensitivity: detection of small amounts of immunoglobulin molecules and the importance of different detection systems. AB - The original method of the dot assay described by Hawkes et al. enabled the detection of 100 pg of immunoglobulin molecules. We compared different enzyme detection systems based on the avidin-biotin complex, in conjunction with different substrates. Three commercial kits (Vectastain-ABC, Streptavidin Bridge, and Streptavidin-Peroxidase Complex) based on the same technique were also included in the comparison. In addition, we tested the Aureo-Probe kit, which is based on gold- and silver-enhanced staining. Various incubation times, blocking solutions (horse serum, bovine serum albumin, and milk), and commercial antihuman Ig antisera or monoclonal antibodies were tested. The greatest sensitivity was achieved by using the peroxidase-avidin-biotin complex together with 4-chloro-1 naphtol as substrate, which detected 1 pg of immunoglobulin molecules. Equal sensitivity was also shown by the Aureo-Probe system. PMID- 2202796 TI - Effectiveness of testing for anti-DNA and the complement components iC3b, Bb, and C4 in the assessment of activity of systemic lupus erythematosus. AB - Seventy-one patients with systemic lupus erythematosus (SLE), seen in an outpatient setting for follow-up evaluation during a 3-mo period, were tested (in addition to routine lupus monitoring studies) with enzyme immunoassays (EIAs) for anti-DNA, iC3b, and factor Bb to determine the relationship of these test results to disease activity. SLE activity was scored by four previously reported scoring systems, and six patients were identified as active by all four systems. We found that the EIA for anti-DNA was the best indicator of disease activity and that iC3b and Bb were not informative for this purpose in this group of patients. Mean iC3b levels were higher in a subset of seven patients with past biopsy evidence of severe (WHO class IV) glomerulonephritis than in the rest of the study population, even though none of these patients had active disease at the time of this study. PMID- 2202797 TI - Precision of the islet-cell antibody assay depends on the pancreas. AB - Several workshops attempting to standardize the islet-cell antibody (ICA) assay have demonstrated marked but unexplained interlaboratory variation. In this study, the effect of using 10 different pancreata to quantitate ICA in a standardized two-color immunofluorescence test within the same laboratory was evaluated. Sera from 11 recent-onset insulin-dependent diabetic patients and one healthy control were analyzed. The negative control serum was recorded as ICA negative in all 10 pancreata. The ICA end-point titers varied, with 1.1-2.4 titration steps in standard deviations in the 10 different pancreata. The interassay variability within the same pancreas was 0.6-0.9 titration steps and therefore could not alone explain the interpancreatic variation. The end-point titers in the different pancreata were highly correlated (rs = 0.71-1.0), supporting the hypothesis that the pancreatic tissue strongly influences the ICA levels. A quality index was developed for selection of pancreata with qualities for ICA analyses. The international ICA standard serum used to express the results in Juvenile Diabetes Foundation units diminished the interpancreatic variability. PMID- 2202798 TI - Current status of clinical laboratory tests for the human immunodeficiency virus. AB - The predictive values of positive and negative test results for human immunodeficiency virus (HIV) antibody are extremely high in laboratories that have good quality control and high performance standards and use licensed FDA approved enzyme immunoassay (EIA) and Western blot standardized tests. With a carefully designed protocol, the false-positive rate of combined EIA and Western blot has been reported to be as low as 1 in 10(5). When results of HIV confirmatory antibody tests are indeterminate, other tests such as culture and nucleotide probe methods for HIV DNA or RNA may help resolve false-reactive screening EIA tests. Improvements are constantly in progress for HIV laboratory tests with the use of recombinant DNA-derived antigens and synthetic polypeptides. With the use of new-generation synthetic polypeptide antigens, specific assays to identify HIV-1 and HIV-2 have been developed. Recently, assays for the HIV regulatory gene products have been studied for their predictive potential. Antibodies to nef protein, a regulator of HIV-1 replication, may be an early indicator of HIV infection. PMID- 2202799 TI - Monocyte chemoattractants produced by malignant cells. PMID- 2202800 TI - Cellular functions of adhesion molecules. PMID- 2202801 TI - The c-erb B-2 proto-oncogene in human pancreatic cancer. AB - The c-erb B-2 oncogene encodes a 190 kD transmembrane growth factor receptor which is closely related to the EGF receptor and has been found to be amplified and overexpressed in a number of human adenocarcinomas, particularly of the breast. We have analysed, by immunocytochemistry using the 21N antibody, expression of c-erb B-2 in a retrospective series of pancreatic adenocarcinoma, chronic pancreatitis, and examples of histologically normal pancreas. In three cases (21 per cent) of chronic pancreatitis, there were focal areas of cytoplasmic immunoreactivity in regenerating epithelium. In 15 cases (17 per cent) of pancreatic adenocarcinoma, cytoplasmic immunoreactivity was seen, while in two cases (2 per cent) strong membrane staining of tumour cells was seen which could be blocked by peptide controls. c-erb B-2 immunoreactivity was also demonstrated using a second antibody, 20N, which recognizes another peptide sequence of the c-erb B-2 protein. There was no relationship between immunoreactivity and histological subtype or grade, but there was absolute concordance between staining in primary and metastatic deposits. Since the rat homologue (neu) of the c-erb B-2 oncogene may be activated by a specific point mutation in its transmembrane region, we have analysed 23 cases from this series for mutations by polymerase chain reaction amplification and sequence-specific oligonucleotide hybridization. We were unable to identify activity mutations in this series. These data suggest that there is abnormal expression of c-erb B-2 oncogene in nearly 20 per cent of cases although mutational activation of this gene is not seen in human pancreatic adenocarcinoma. PMID- 2202802 TI - Glucose therapy for glycogenosis type 1 in infants: comparison of intermittent uncooked cornstarch and continuous overnight glucose feedings. AB - This study was undertaken to test the glycemic response of five infants with glycogen storage disease type 1, aged 0.7 to 1.5 years, to uncooked cornstarch under various dietary conditions, and to evaluate the long-term effects of a dietary regimen consisting of uncooked cornstarch in milk every 4 hours, in addition to three meals daily, on biochemical values and physical growth. The results were compared with previous experience in treating six infants with continuous overnight glucose infusion via gastrostomy plus multiple daily feedings containing an adequate source of glucose. A test dose of cornstarch (1.6 to 1.8 gm/kg) providing four times the calculated hourly glucose production rate, when given in water 15 to 30 minutes after a continuous overnight intragastric glucose infusion was stopped, did not maintain normoglycemia. When the same dose was given in 2% cow milk 4 hours later, mean blood glucose levels remained greater than 68 mg/dl (3.8 mmol/L) for up to 4 hours. A regimen of uncooked cornstarch in 2% cow milk at 4-hour intervals in addition to three meals daily prevented hypoglycemia, and maintained blood lactate at nearly normal levels and serum uric acid and cholesterol within the normal range; triglyceride levels were increased only modestly. Overnight blood glucose levels were comparable to those achieved with continuous intragastric glucose infusion. With this regimen the five infants have maintained linear growth rates normal for their age and genetic potential; the mean percentage of ideal body weight for length percentile did not change significantly, although two of the five patients were overweight (123% and 124% of ideal body weight respectively) after 3 years of treatment. We conclude that a trial of uncooked cornstarch in feedings of milk every 4 hours should be attempted as soon as a more frequent feeding schedule with dextrose-containing formulas proves ineffective, because the former has the potential to provide the continuous glucose required by infants with glycogen storage disease type 1 in a safer and less invasive fashion than continuous intragastric glucose infusion. PMID- 2202803 TI - Crohn disease in an infant with central nervous system thrombosis and protein losing enteropathy. PMID- 2202804 TI - Double-blind, randomized trial of diazepam versus placebo for prevention of recurrence of febrile seizures. AB - The aim of this study was to evaluate the efficacy and tolerance of intermittent oral administration of diazepam during hyperthermia for reducing the recurrence of febrile seizure: 185 children, between 8 months and 3 years of age, with a first febrile seizure and normal neurologic development, were randomly assigned in a double-blind fashion to receive orally administered diazepam (0.5 mg/kg, then 0.20 mg/kg, every 12 hours) or placebo, whenever the rectal temperature was more than 38 degrees C. The main criterion of efficacy was the seizure recurrence rate 1 year after the first seizure. The duration of the study was 3 years; eight different centers in France participated. There were 462 febrile episodes and 1000 days with prophylactic treatment. The recurrence rates did not differ between the diazepam group (16%) and the placebo (19.5%) group. The children with recurrent seizures were significantly younger at the time of the first seizure (17 +/- 6.9 months) than children without a recurrent seizure (21 +/- 8.5 months). In children with recurrent seizures, prophylactic treatment was correctly administered to only 1 of 15 children in the diazepam group and to 7 of 18 children in the placebo group. The following were the reasons for this poor cooperation: convulsion being the first manifestation of the fever (seven cases in each group), parents neglecting to give treatment (nine cases), and refusal to take treatment by two children. Side effects were similar in the two groups except for hyperactivity, which was more frequent in the diazepam (138 days) than in the placebo (34 days) group. Intermittent oral administration of diazepam at the onset of fever offered no advantage over placebo in preventing recurrence of seizure. This finding probably reflects a lack of efficacy of the intermittent method rather than of diazepam itself. PMID- 2202805 TI - Restricted diets for treatment of migraine. PMID- 2202806 TI - Phakomatous choristoma: clinical, histopathologic, and ultrastructural findings in a 4-month-old boy. AB - A case of phakomatous choristoma of the lower eyelid is described. A survey of previously reported cases reveals a characteristic and consistent clinical and morphologic picture. Universally the patient presents in infancy with a rather small, firm, rubbery nodule attached to the lower edge of the inferior tarsal plate. Always present in the nasal aspect of the lower lid, the tumor is easily palpable. Recognition of this clinical picture may allow the ophthalmologist to suspect the appropriate diagnosis, but the final diagnosis should be based on the recognition of characteristic histopathology. PMID- 2202807 TI - The effects of scaling a titanium implant surface with metal and plastic instruments: an in vitro study. AB - The surface roughnesses of pure titanium implants were compared with scaling in vitro with curettes of dissimilar composition. Each of 10 transmucosal implant extensions (TIEs) was divided into three experimental surfaces and an untreated control surface. The three experimental surfaces were instrumented with either a titanium-alloy tipped curette, a curette of stainless steel, or a plastic curette. All experimental surfaces received 30 strokes with the designated curette within a 2 mm wide area. Alteration of the surfaces due to instrumentation was evaluated by a helium neon (HeNe) laser and reported as relative specular reflectance (RSR). Scanning electron microscopy (SEM) conformed the quantitative HeNe laser results. A significant decrease in mean RSR (greater roughness) was observed for surfaces treated by metal curettes compared to either untreated control surfaces (P less than 0.01) or surfaces treated by the plastic curette (P less than 0.01). No statistically significant difference was noted between untreated surfaces and those treated by the plastic curette. The titanium alloy curette produced a significantly lower mean RSR (greater roughness) compared to those surfaces treated by the stainless steel curette (P less than 0.05). In summary, plastic instruments produced an insignificant alteration of the titanium implant surface following instrumentation, while metal instruments significantly altered the titanium surface. PMID- 2202808 TI - The effects of scaling titanium implant surfaces with metal and plastic instruments on cell attachment. AB - This study examined the ability of tissue culture fibroblasts to attach and colonize on the surface of pure titanium dental implants following instrumentation of the implant surface with curettes of dissimilar composition. Pure titanium dental implants were scaled with a plastic, titanium-alloy, or stainless steel curette and then immersed in a cell suspension of 3T3 fibroblasts. Counts of attached cells were made at 24 and 72 hours; the implants were then processed for scanning electron microscopy (SEM). At 24 hours, only surfaces scaled with a stainless steel curette showed a significant reduction in number of attached cells relative to untreated control surfaces. At 72 hours, both stainless steel and titanium-alloy curette instrumented surfaces showed significantly fewer attached cells than untreated control surfaces, with the greatest reduction in cell attachment observed on the stainless steel curette instrumented surfaces. SEM observations showed that fibroblasts on stainless steel instrumented surfaces tended to show a somewhat rounded morphology and a relatively reduced degree of spreading: while fibroblasts on untreated control, plastic, or titanium-alloy instrumented surfaces showed a well-spread, polygonal morphology, more typical of fibroblasts in favorable culture conditions. To the extent that such observations of cell attachment and morphology are indicative of in vivo biocompatibility, these findings could have clinical implications for the proper maintenance of titanium dental implants. PMID- 2202809 TI - Susceptibility of oral bacteria to phenoxyethanol and phenoxyethanol/chlorhexidine combinations. AB - A total of 57 bacterial strains (26 different species) which may be isolated from subgingival plaque were tested for their in vitro susceptibility to phenoxycthanol, a commonly-used antiseptic and preservative. Ninety-five percent of the strains, including those associated with chronic inflammatory periodontal disease, were susceptible to concentrations of phenoxyethanol used topically (2% w/v). Phenoxyethanol at a concentration of 1% (w/v) was also found that to have a rapid bactericidal effect achieving a 99.9% kill in 5 minutes or less for species such as Bacterodides gingivalis, Fusobacterium nucleatum, Eikenella corrodens, and Wolinella recta. Addition of chlorhexidine to phenoxyethanol resulted in a mixture with increased antibacterial activity. For most bacterial strains, the presence of chlorhexidine resulted in at least a four-fold decrease in the concentration of pheoxyethanol required for inhibition of growth. These results imply that phenoxyethanol may be useful in the treatment of chronic inflammatory periodontal disease either by itself or in combination with chlorhexidine. PMID- 2202810 TI - Sex differences in the personality and cognitive correlates of spatial ability. AB - Ozer (1987) found that spatial visualization correlated with personality and verbal ability for girls but not for boys. To account for this finding, he hypothesized that "the causes of individual differences in spatial visualization [may be] different for the two sexes" (Ozer, 1987, p. 134). Although Ozer's conclusion is an intriguing one, it should be viewed with at least some skepticism until the discrepancies between his data and those of other researchers have been reconciled. PMID- 2202812 TI - The ceramic reverse three-quarter crown for anterior teeth: laboratory procedures. AB - The laboratory procedures for making a Hi-ceram porcelain anterior reserve three quarter crown are described. A core of high-fusing aluminum oxide is used as a coping on which tooth contours are restored with a compatible porcelain. Standard dental laboratory equipment is used and the technique can be quickly learned by any experienced ceramics technician. PMID- 2202811 TI - Two distinct types of inwardly rectifying K+ channels in bull-frog atrial myocytes. AB - 1. Single atrial myocytes were enzymatically isolated from the bull-frog as previously described (Hume & Giles, 1981), and patch-clamp techniques were used in an attempt to identify and separate two inwardly rectifying K+ channels in this tissue. 2. Single-channel measurements consistently demonstrated the existence of two different resting K+ channels, which both exhibited strong inward rectification. The unitary conductances of these K+ channels were 34 +/- 4 and 22 +/- 3 pS (mean +/- S.D., at 22-24 degrees C) when measured with 110 mM-K+ in the pipette solution, and their mean open times were 0.87 +/- 0.33 and 129.9 +/- 49.4 ms, respectively. 3. In the absence of acetylcholine (ACh) in the pipette, openings of the larger channels with the shorter open times occurred at a very low frequency. When ACh was present in the patch pipette, the activity of this channel increased significantly, although the single-channel conductance and gating behaviour were very similar either with or without ACh in the pipette. 4. The zero-current voltage (extrapolated from the inward currents through these types of channels) depended on the extracellular K+ concentration. [K+]o, in the fashion expected for a predominantly K(+)-selective channel: it shifted by 58 mV for a tenfold change in [K+]o. Very similar results were obtained from whole-cell voltage-clamp measurements (53 mV for a tenfold change in [K+]o). 5. The conductance of both types of K+ channels depended on [K+]o. The single-channel conductances were 25 +/- 3 and 13 +/- 2 pS with 50 mM [K+]o, and 19 +/- 4 and 9 +/- 2 pS with 20 mM [K+]o, respectively. 6. These results demonstrate that two types of resting inwardly rectifying K+ channels can be identified in single atrial myocytes. One of these is an inwardly rectifying K+ channel (IK1) previously identified in whole-cell voltage-clamp experiments (Hume & Giles, 1983). The second channel is the muscarinic receptor-regulated K+ channel (IK(ACh) which was first described in mammalian nodal and atrial cells. 7. N Ethylmaleimide (NEM), a reagent which alkylates sulphydryl groups, affects these two types of K+ channels differentially. In the cell-attached patch configuration, bath application of NEM (50 microM) completely abolished the activity of IK(ACh), without affecting the IK1 channel activity. 8. To obtain further evidence that these two currents, IK1 and IK(ACh), were different, the inside-out patch-clamp technique was used.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2202813 TI - The effect of cavity pretreatment procedures on dentin bonding: a four-year clinical evaluation. AB - Cervical abrasion and erosion lesions were restored with composite resin restorations bonded with four different dentin-bonding resins, an enamel-bonding resin, or restorations of a glass ionomer cement. The long-term clinical retention of the restorations were evaluated during a 4-year period. The surrounding enamel was not acid-etched. Four cleaning methods for dentin pretreatment were used to study their effects on the bonding between dentin and the restorative materials. The dentin was treated with either (1) etching for 60 seconds or (2) 15 seconds with 37% phosphoric acid, (3) cleaning with 5% sodium hypochlorite (NaOCL) for 20 seconds, or (4) cleaning with Tubulicid etchant for 60 seconds. None of the composite resin restorations, regardless of pretreatment or bonding method, showed acceptable restorations. All glass ionomer cement restorations were retained after pretreatment with Tubulicid etchant and 5% NaOCL after a 6-month period. Full acceptance, in other words, 3 year retention, was reached only after pretreatment with NaOCL. PMID- 2202814 TI - Changes in retention of various telescope crown assemblies over long-term use. AB - An investigation was done on the effect of crown height, angle (one-half taper) and number of removals on the retention of telescope crowns. Assemblies of inner and outer crowns were constructed on master dies. Crown heights of 4 mm, 5 mm, and 6 mm were used. Cone angles of 0, 2, 4, and 6 degrees were used for each of the three heights. The inner crowns were fixed to the dies with an adhesive agent. the outer crowns were set over them and placed in a clamp. Separation forces were tested with an Instron machine (Instron Corp., Canton, Mass.). They were measured initially and after numerous 100 insertion/separation cycles up to 1000 cycles and numerous 500 insertion/separation cycles up to 10,000 cycles. The results demonstrated that the cone angle of the inner crown was more important than its height for maximum retention. Retention is rapidly lost after the cone angle exceeds 2 degrees. It was also shown that an accessory device is necessary to maintain retention capabilities after long-term use. PMID- 2202815 TI - Interfacial strengths of various alloy surface treatments for resin-bonded fixed partial dentures. AB - A practical method for bonding or rebonding the resin-bonded retainer is eagerly being sought by general practitioners. This research introduces a new test apparatus for evaluating bond strength of base metal alloys after various alloy surface treatments. Five commercial base metal alloys and a resin luting cement for resin-bonded fixed partial dentures were examined. Sandblasting, oxidation, or etching treatment were determined to be effective in increasing the adhesive strength for the tested alloys. No statistical differences between various surface treatments were found for bonding of Unitbond metal. Inexpensive sandblasting, along with ultrasonic washing, provided superior bonding strengths for Biobond II and Litecast B materials. Electrochemical treatment was suitable for Wiron 77 and Lab metals. PMID- 2202816 TI - Comparison of the effects of three sprue designs on the internal porosity in crowns cast with a silver-free high-palladium alloy. AB - This study tested the effect of bsprue design on internal porosity of a silver frees high-palladium alloy. The designs evaluated consisted of: (1) a cylindrical sprue, (2) a cylindrical sprue with a reservoir, and (3) cylindrical sprue with a constriction at the point of attachment with the pattern. Ten identical complete crowns were made with each sprue design. The cast crowns were embedded in epoxy resin, sectioned, and polished. A total of six sites for each sample were analyzing computer. The mean amount of internal porosity from all analyzed sites for each sprue design was calculated as a percent site porosity per total site and differences between the experimental sites and groups tested. The analysis of variance found no significant differences among the sprues and no significant interaction, but determined a significant difference (p less than 0.05) among the sites analyzed. Tukey's studentized range test showed that the sprue contained a significantly greater percentage of porosity than any of the other sites analyzed. PMID- 2202817 TI - Modification of immediate denture sectional impression technique using vinyl polysiloxane. AB - The labial sectional impression technique in the maxillary immediate denture can be done in many different materials with varied results. The use of vinyl polysiloxane putty for this impression technique is demonstrated and shows the superior results both in the ease of use and the detail of the impression surface. PMID- 2202818 TI - The longitudinal clinical effectiveness of osseointegrated dental implants: the Toronto study. Part III: Problems and complications encountered. AB - Two hundred seventy-four implants were placed in 49 dental of 46 consecutively treated patients. The success rate for individual implants in this study, 4 to 9 years after placement, was 89.05% and for the prosthetic treatment it was 100%. Problems, and complications were observed and recorded at stage I surgery, between stage I and stage II surgery, at stage II surgery, and in the healing period that followed. Also noted were the complications subsequent to prosthodontic treatment and during the years of follow-up. Virtually al of the problems encountered were iatrogenic in nature. These clinical results indicate a safe retrievable technique with negligible associated morbidity. PMID- 2202819 TI - Stress-absorbing elements in dental implants. AB - By means of finite element analysis, calculations, were made of the stress distribution in bone around implants with and without stress-absorbing elements. A freestanding implant and an implant, it was concluded the variation in the E modulus of the stress-absorbing element had no effect on the stresses in bone. Changing the shape of the stress-absorbing element had little effect on the stresses in cortical bone. For the implant connected with a natural tooth, it was concluded that a more uniform stress was obtained around the implant with a low E modulus of the stress-absorbing element. It was also concluded that the bone surrounding the natural tooth showed a decrease in the height of the peak stresses. PMID- 2202820 TI - Number and location of occlusal contacts in intercuspal position. AB - Records of intercuspal position were made in 45 healthy young adults with morphologically normal occlusions. The observed perforations were analyzed according to the frequency of occlusal contacts. Most subjects had asymmetric distribution in number and location of occlusal contacts. Regardless of symmetry, a significantly higher number of subjects had approximately seven contacts on each side that were located between all posterior teeth. Contacts were most frequent between maxillary and mandibular first and second molars. PMID- 2202821 TI - Comparison of vertical morphologic measurements on dentulous and edentulous patients. AB - Through an analysis of cephalometric films, the vertical dimension of occlusion of a group of edentulous patients was compared with the vertical dimension of occlusion in a previously studied group of dentulous patients. In addition, the vertical dimension of occlusion in the edentulous group was measured after 20 years of denture wearing. The results indicated a remarkable correlation in the vertical dimension of occlusion established initially for the endentulous patients when compared with the measurements made for dentulous patients of a similar age range. The mean change in the vertical dimension of occlusion after 20 years of wearing complete dentures was 2.5 mm. PMID- 2202823 TI - Interim acrylic resin duplicate removable partial dentures. AB - Certain dental procedures require patients to be without their removable partial dentures. This can be a great inconvenience and psychologically difficult for some patients. This procedure permits duplicating existing removable partial dentures so that patients will not have to be without prostheses. PMID- 2202822 TI - The presence and identification of organisms transmitted to dental laboratories. AB - The potential for infection of dental personnel in the office and dental laboratory by transmission of microorganisms between dentists' offices and commercial dental laboratories does exist. Sixty-seven percent of all materials sent from dental offices to dental laboratories sampled in four cities were contaminated with bacteria of varying degrees of opportunistic pathogenicity. Dental offices and dental laboratories need to practice adequate infection control procedures to prevent possible cross-contamination. PMID- 2202824 TI - Resin-bonded fixed partial dentures for abutment teeth with existing occlusal restorations. PMID- 2202825 TI - An index of chewing ability. AB - This study was carried out to develop and test an index of chewing ability suitable for epidemiologic surveys. Existing data on older adults living independently in East York, Ontario, were reanalyzed and the index was developed using techniques of scalogram analysis. Individuals were scored from 0 to 5 based on their self-reported ability to chew the most difficult of five foods. In this representative sample, 77 percent scored 5. The index has high predictive values when compared to two other questions on chewing ability in the survey. Among those with chewing disability (scoring 0 to 4), the odds ratio (OR) for being edentulous was 4.1 (95%) Cl = 2.1-8.3). No factor influenced chewing ability among the edentulous. Among the dentate, several clinical dental health status measures appeared to influence chewing ability. Logistic analysis identified the absence of functioning opposing pairs of natural posterior teeth, OR 5.6 (95% Cl = 2.21-14.39), and the need for urgent care, OR 23.7 (95% Cl = 1.05-6.95), as the most important. PMID- 2202827 TI - Alfred Burger award address. Bioactive alkaloids. 4. Results of recent investigations with colchicine and physostigmine. PMID- 2202826 TI - Issues in financing dental care for the elderly. AB - The elderly make up an increasingly larger segment of the patient population in dental practices. This article reviews recent epidemiologic, demographic, and health services research, and concludes that significant segments of the elderly are at high risk for oral disease and/or limited access to dental treatment, and consequently warrant classification as high-risk groups for policy considerations. It then proposes policy options to the dental community and public decision makers. Oral care can be viewed as having three components. Two basic components are the primary care component--which includes diagnostic, preventive restorative, and periodontal care--and the acute care component--i.e., the treatment of oral pain, trauma, and infection. The third, rehabilitative component, has to do with the restoration of oral function, including prosthodontics and cosmetic dentistry. Viewing dental care in this perspective may help link funding for dental primary care services with that for other primary health services, and link restoration of function and improvement of quality of life with similar health services, like hearing, vision, and social services. In addition, approaching dental care policy makers on several levels- i.e., federal, state, and local--will contribute to our ability as a profession, in the decades ahead, to meet the oral health needs of more elders: including the frail, those at high risk for oral disease, and those with limited access to care. PMID- 2202828 TI - Novel inhibitors of human renin. Cyclic peptides based on the tetrapeptide sequence Glu-D-Phe-Lys-D-Trp. AB - Cyclic peptide inhibitors of human renin based on a linear peptide, Boc-D-Phe Cys(Acm)-D-Trp-Leu-OMe (1), were prepared by solution-phase methods. Potent inhibitors were obtained in one series of compounds, Z-Glu-D-Phe-Lys-D-Trp-Leu OMe (3), in which the D-phenylalanine residue was incorporated in a 15-membered ring structure. Any reductions or enlargements of the ring size led to inactive or less potent peptides. The most potent inhibitor of human renin, Me3CCH2-Glu-D Phe-Lys-D-Trp-NH(CH2)2CHMe2 (31) (IC50 6.3 x 10(-8) M), was obtained by changing N- and C-terminal parts of pentapeptide 3. It was about 650-fold more potent than linear tetrapeptide I and about 50-fold more potent than cyclic peptide 3. Compound 31 was also 112-fold more potent against human renin than against porcine renin. PMID- 2202829 TI - Inhibitors of human renin. Cyclic peptide analogues containing a D-Phe-Lys-D-Trp sequence. AB - Cyclic peptides containing a D-phenylalanine and a D-tryptophan residue have been synthesized and tested as inhibitors of human renin. Most of these are tripeptide derivatives of the type CO(CH2)3CO-D-Phe-Lys-D-Trp- or COCH2NHCH2CO-D-Phe-Lys-D Trp- in which the individual side-chain methylene groups have been replaced with CHMe-, -CMe2-, -CH(Ph)-, -CH(CH2Ph)-, or -CH[CH2)2CHMe2)-groups. The three amino acid residues and the size of the ring were very important features of these compounds. Reducing the ring size gave much less potent compounds. The most potent analogue of the series, CO(CH2)2CHPhCO-D-Phe-Lys-D-Trp-NH(CH2)2CHMe (14, IC50 = 26 nM), was obtained by substituting the methylene group nearer to the D Phe residue by a -CHPh- group. Compound 14 was 15-fold more potent in inhibiting human renin than porcine renin. PMID- 2202830 TI - Neural networks applied to quantitative structure-activity relationship analysis. AB - An application of the neural network to quantitative structure-activity relationship (QSAR) analysis has been studied. The new method was compared with the linear multiregression analysis in various ways. It was found that the neural network can be a potential tool in the routine work of QSAR analysis. The mathematical relationship of operation between the neural network and the multiregression analysis was described. It was shown that the neural network can exceed the level of the linear multiregression analysis. PMID- 2202831 TI - Antimalarial activity of new water-soluble dihydroartemisinin derivatives. 3. Aromatic amine analogues. AB - A series of artemisinin (1) derivatives containing bromo and heterocyclic or aromatic amine functions was prepared in the search for analogues with good water solubility and high antimalarial activity. Treatment of dihydroartemisinin (2a) with boron trifluoride etherate at room temperature gave the key intermediate, 9,10-dehydrodihydroartemisinin (3), which, on reaction with bromine, gave the dibromide 4. The latter was condensed with amines in anhydrous CH2Cl2 at less than -10 degrees C to give the desired products in 25-55% yield. The new derivatives, tested in vitro against Plasmodium falciparum, were found to be more effective against W-2 than D-6 clones and were not cross-resistant with existing antimalarials. Compound 6b, 3-fluoroaniline derivative, was the most active of the series, with the IC50 less than or equal to 0.16 ng/mL, making it several fold more potent than 1. However, no significant in vivo antimalarial activity against Plasmodium berghei was observed in any of the new compounds tested. PMID- 2202832 TI - Sensitivity to endotoxin is induced by increased membrane fatty-acid unsaturation and oxidant stress. AB - The mechanisms modulating host susceptibility to endotoxin are unknown. Evidence suggests that endotoxin pathophysiology is mediated in part by oxidative reactions that lead to tissue damage and organ failure. The proposition is that conditions which favour oxidation sensitise the host to endotoxin. Central to this hypothesis is that an increase in the polyunsaturated fatty-acid composition of membrane phospholipids enhances susceptibility because such fatty acids are easily oxidised to produce mediators of the endotoxic crisis. Cytokines, such as tumour-necrosis factor and interferon-gamma, may be ultimately responsible for orchestrating these changes and thereby modify the host response to endotoxin. PMID- 2202833 TI - Resistance to metal ions and antibiotics in Escherichia coli isolated from foodstuffs. AB - Of 39 strains of Escherichia coli isolated from foodstuffs, all were resistant to at least one of a panel of four metallic ions tested. The most common resistance (94.9%) was against cadmium, followed by arsenate (76.9%), silver (71.8%) and mercury (61.5%). Multiple resistance to three (35.9%) or four (38.5%) metals was seen more often than resistance to two (18%) or one (7.7%) metal only. The opposite trend was seen in antibiotic resistance; resistance to one (30%) or two (49%) antibiotics was more common than to three or more antibiotics (13%). Resistance to kanamycin correlated with resistance to silver and cadmium ions and resistance to ampicillin or cephalothin was, with one exception, associated with resistance to cadmium ions. PMID- 2202834 TI - An enzyme immunoassay for detecting Cryptosporidium in faecal and environmental samples. AB - An enzyme immunoassay (EIA) with a monoclonal antibody to cryptosporidium oocysts was developed and evaluated for the examination of faecal and environmental samples. The EIA was as sensitive as microscopy for detecting Cryptosporidium but also produced some positive results which could not be confirmed by a modified Ziehl-Neelsen technique or by immunofluorescence microscopy. These specimens reacted also with heterologous antibodies in EIA, suggesting false positive results. PMID- 2202835 TI - Efficiency of sand filtration for removing cryptosporidium oocysts from water. AB - Purified oocysts of Cryptosporidium were applied to the top of a sand filter which had been constructed in the laboratory. The filter was eluted with distilled water; fractions were collected and examined for Cryptosporidium by modified Ziehl-Neelsen technique and immunofluorescence microscopy and by an enzyme immunoassay. The results indicate that oocysts of Cryptosporidium do not easily pass through the sand filter, and that some disintegration of oocysts may occur during filtration. PMID- 2202836 TI - Detection of diphtheria toxin in culture supernates of Corynebacterium diphtheriae and C. ulcerans by immunoassay with monoclonal antibody. AB - Monoclonal antibody (MAb) to diphtheria toxin was produced in mouse hybridomas, and shown by ELISA to be of sub-class IgG1. Hybridomas were inoculated into mice to produce ascitic fluid from which MAb was purified by caprylic acid. The MAb was shown by immunoblotting to be directed against the A fragment of the toxin and also against the intact toxin molecule. After conjugation with fluorescein isothiocyanate, it was used in an immunoassay to detect toxin in culture supernates of Corynebacterium diphtheriae and C. ulcerans. The assay correlated well with the Elek test and with virulence in guinea-pigs; but it gave occasional false positive results, probably by binding of MAb to defective toxin. PMID- 2202837 TI - Pyrolysis-mass spectrometry (Py-MS) for the rapid epidemiological typing of clinically significant bacterial pathogens. AB - Fresh clinical isolates of Salmonella spp. and Streptococcus pyogenes were analysed by pyrolysis-mass spectrometry (Py-MS). The results formed the basis of mathematically derived characterizations of individual strains and these were compared with the results of phage typing for the salmonellas and M protein typing for the streptococci. Py-MS was shown to be a rapid and reproducible method for inter-strain comparisons, giving evidence of identity and non-identity between strains that agreed well with the results of conventional tests. Py-MS has potential value as a rapid, relatively inexpensive and highly discriminatory method of epidemiological analysis in bacterial disease. PMID- 2202838 TI - A critical appraisal of the predictive value of in vitro chemosensitivity assays. AB - The ultimate value of a screening program based on the response of cell lines in vitro will depend on the demonstration of a strong correlation between in vitro and in vivo responses to cytotoxic drugs. However, marked discrepancies in the predictive value of in vitro chemosensitivity assays have been described, suggesting that factors other than the inherent chemosensitivity of tumor cells significantly influence the outcome of chemotherapy in vivo. These factors include the influence of drug pharmacokinetics and metabolism, together with numerous problems associated with the biology of solid tumors in vivo (e.g., drug penetration barriers, proliferation gradients, and microenvironmental conditions). These additional factors may be highly significant in explaining the site-dependent nature of the responses of solid tumors to cytotoxic drugs, the poor prediction of responses in experimental tumor models, and the differences in the responses of multicellular spheroids and monolayers. These discrepancies suggest that the selection of compounds for phase II clinical trials on the basis of disease-specific activity in vitro may be premature. PMID- 2202839 TI - Childhood shigellosis: clinical and bacteriological study. AB - Ninety-three children with shigellosis were hospitalized in a regional hospital in Kuwait during the year 1988. S. flexneri was the most common isolate (54%) followed by S. sonnei (39%) and S. boydii (7%). In addition to the gastrointestinal manifestations, 14 patients (15%) developed generalized convulsions. The benign and self-limiting nature of the convulsions associated with shigellosis means that neither diagnostic procedure nor drug therapy are usually necessary. The disease was self-limiting in 41% and antimicrobial usage did not seem to shorten the duration of symptoms or hospital stay. All shigellae isolated were sensitive to gentamicin and amikacin, 56% were resistant to three or more antimicrobial agents, 32 were resistant to five or more. These findings may indicate the need for better control of antibiotic use, particularly in developing countries. PMID- 2202840 TI - Correlation between human and animal bio-serogroups of Campylobacter isolates in Nigeria. AB - Campylobacter enteritis is endemic in Nigeria as in most other developing countries of the world. This paper examines the common biotypes and serogroups of Campylobacter in human and animal isolates. The observed correlation suggests a possible animal to human route of infection in Nigeria. Implications on preventive and control measures are discussed. PMID- 2202841 TI - Isolated malaria outbreak in Somalia: role of chloroquine-resistant Plasmodium falciparum demonstrated in Balcad epidemic. AB - A study was conducted in Balcad in December 1988 during a reported outbreak of malaria in order to investigate possible factors contributing to the outbreak. The slide positivity rate of 71% among fever patients, which was significantly higher than the usual rate, suggests the existence of a fresh malaria outbreak in the area. High parasite densities together with the pronounced malaria symptoms among both resident children and adult immigrants indicated little, if any, malaria experience in these patients. This outbreak could not be explained by gross climatic changes, e.g. unusual rainfalls. The in-vivo response of P. falciparum to the standard therapeutic regimen of chloroquine showed a high degree of resistance, with 31 of 36 patients showing resistance, including five RI responses and 26 RII-RIII responses. Micro in-vitro tests for chloroquine susceptibility showed resistance in 33 out of 37 isolates with a mean EC50 and EC99 of 1.50 and 10.97 X 10(-6) mol l-1 blood, respectively, indicative of a high degree of chloroquine resistance. All isolates tested against sulphadoxine/pyrimethamine showed a sensitive response. The frequent presence (78%) of detectable chloroquine levels prior to treatment did not apparently alter the in-vitro parasite growth. This is a sign of widespread use of this drug resulting in a high 'drug pressure' in the area. The proportion of sensitive parasites was inversely related to the pretreatment chloroquine concentration providing evidence of the selection of resistant parasites by the previous drug intake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2202842 TI - NIH consensus conference. Adjuvant therapy for patients with colon and rectal cancer. PMID- 2202843 TI - [Pharmacokinetics and clinical studies of norfloxacin in the pediatric field]. AB - Norfloxacin (NFLX) tablets with a potency of 50 mg/tablet or 100 mg/tablet were administered at doses of 1 to 4 tablets (1.5 to 6.1 mg/kg) orally 30 minutes before meals to 12 children with ages ranging from 8 years 9 months to 12 years 5 months, and serum/urinary NFLX levels and urinary recovery rates were determined. The drug sensitivity tests for NFLX and 10 other drugs were conducted against 128 strains of Shigella sonnei (10(6) CFU/ml) which had been isolated from pediatric patients with bacillary dysentery. In order to evaluate clinical and bacteriological effects of NFLX and its safety in the pediatric field, NFLX 50 mg tablets were administered t.i.d. (mean 8.3 mg/kg) for 5 days to 42 pediatric patients with bacillary dysentery. Similarly, this drug was administered in b.i.d. or t.i.d. (mean 6.7 mg/kg) for 4 days to 4 pediatric patients with urinary tract infections. The following results were obtained: 1. According to the dosage, the subjects were divided into 3 groups with dose levels 1.5-2.8 mg/kg, 3.1-4.7 mg/kg and 5.2-6.1 mg/kg. These groups had 5, 2 and 5 subjects, respectively. Mean serum drug concentrations for the 3 dosage groups were at peak levels of 0.27, 0.64 and 1.51 micrograms/ml at 4, 2 and 1 hour(s) after administration, respectively. Pharmacokinetic parameters for these dosage groups were as follows: Tmax values were 3.0, 3.0 and 1.2 hours; Cmax values were 0.32, 0.78 and 1.56 micrograms/ml; serum half-lives were 2.2, 2.4 and 2.3 hours; and AUCs were 1.65, 3.98 and 6.06 micrograms.hr/ml, respectively. Thus, dose dependent responses were observed among the 3 dosage groups. 2. Mean peak urinary drug concentrations for the 3 dosage groups were 45.8, 109.2 and 215.1 micrograms/ml, respectively, and the peaks appeared 2-4 hours after administration. Mean recovery rates up to 8 hours after administration were 18.3%, 24.5% and 28.7%, respectively for the 3 dosages. 3. In a drug sensitivity test against 128 strains of S. sonnei, the most frequent MIC value of NFLX was 0.78 micrograms/ml against 65 strains, followed by 0.39 micrograms/ml for 56 strains. Together, these strains accounted for 94.5% of the strains tested. No resistant strain to this drug was observed and the antibacterial activity of this drug was second only to colistin, similar to that of ofloxacin, better than those of enoxacin and seven other drugs. 4. Clinical efficacy rate of NFLX against bacillary dysentery was 95.2% in 21 cases in which the evaluation was possible.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2202844 TI - Localization of bacterial antigens in calves inoculated orally with ruminal Bacteroides succinogenes and Selenomonas ruminantium. AB - Localization of bacteria and bacterial materials was investigated in calves inoculated orally with live organisms of both Bacteroides succinogenes and Selenomonas ruminantium by a immunohistological method using rabbit antiserum against the outer membrane of those organisms and by a scanning electron microscope. The intact organisms of both inoculated bacterial species were detected on the rumen wall and in the lamina propria of the forestomach, and S. ruminantium also in the lymph nodes associated with the rumen. The bacterial materials were observed inside of macrophage-like cells in the lamina propria of the forestomach and of lymphoid cells in the lymph nodes. Number of the cells in the mesenteric lymph nodes was smaller than that of the forestomach associated lymph nodes. The results suggest that the orally inoculated bacteria may act as antigenical stimulant in the mucosa of the forestomach and associated lymph nodes of calves. PMID- 2202845 TI - Migratory deficiency of Clithon retropictus hemocytes to Vibrio parahaemolyticus and Escherichia coli. AB - Hemocytes of a marine gastropod, Nerita albicilla, but not those of an estuarine gastropod, Clithon retropictus, were observed to migrate to live and heat-killed cells of Vibrio parahaemolyticus and Escherichia coli through Nucleopore membrane in Blind well chamber. The defective migration of C. retropictus hemocytes might reflect, at least in part, the survival of V. parahaemolyticus in the estuarine gastropod. PMID- 2202846 TI - Isolation of Trichophyton verrucosum from soil in cattle breeding environments. PMID- 2202847 TI - Development of a microtest method for serological and virological examinations of chicken anemia agent. PMID- 2202848 TI - Immunohistochemical demonstration of parafollicular (C) cells in sheep thyroid and parathyroid glands. PMID- 2202849 TI - Combination oral contraceptives and cancer risk. AB - Substantial evidence exists to suggest that the use of oral contraceptives alters the risk for some types of cancer. Use of oral contraceptives for one year or more will reduce the risk of endometrial cancer and epithelial ovarian cancer by 50%, with the protective effect lasting for at least 10 years. The risk for developing cervical cancer in women who have used oral contraceptives appears to be slightly increased, although two independent studies actually found a protective effect associated with oral contraceptive use. The protective effect was probably related to the increased screening frequency found in oral contraceptive users and not related to a biologically protective effect. Therefore, women should be encouraged to undergo regular Pap tests. Data regarding breast cancer, in general, show no increased risk associated with oral contraceptive use. The latency associated with the development of breast cancer does not allow a definitive conclusion, and further study will be required. Oral contraceptives appear to increase the risk for developing benign hepatocellular adenoma, but not hepatocellular carcinoma. PMID- 2202850 TI - [Amiodarone: mechanisms of anti-arrhythmic action]. PMID- 2202851 TI - [Founder of the Ural school of therapeutists and cardiologists (on the centennial of B. P. Kushelevskii's birthday)]. PMID- 2202852 TI - [Comparison of antianginal effects of diltiazem and metoprolol in patients with ischemic heart disease with different clinical forms of angina pectoris]. AB - Diltiazem, a new calcium antagonist, and metoprolol, a cardioselective beta adrenoblocker, were comparatively studied in 53 patients with exertional angina and 11 patients with spontaneous angina. A simple blind random method using placebo, graded physical exercise test employing a bicycle ergometer, and Holter monitoring were applied to evaluate the efficiency of the antianginal treatment. A good antianginal effect was exhibited by the both drugs in exercise-induced angina. Diltiazem was found to be effective in 74% of the patients with exertional angina, whereas metoprolol was beneficial in 62%. Unlike diltiazem (85.7%), metoprolol (50.0%) was less potent in spontaneous angina. PMID- 2202853 TI - [Role of a beta adrenergic blocking agent nadolol (corgard) in prevention of arterial hypertension: a 6-month treatment (cooperative study)]. AB - A comparative study was undertaken to examine the long-acting beta-blocker nadolol without intrinsic sympathomimetic activity and reference agents such as anapriline, a beta-blocker, hypothiazide, a diuretic, and pratsiol, a postsynaptic alpha-adrenoblocker in 361 patients with sustained arterial hypertension (diastolic blood pressure, 95 mm Hg or more) in the randomized groups. The therapy was started with monotherapy of one of these drugs; if ineffective, a combination of two or, if necessary, three agents of different groups was given. The patients' status was monitored at least once monthly for 6 months. Monotherapy with beta-blockers or pratsiol was found to be more effective than that with diuretics. Addition of the second agent was required by 48% of the patients, that of the third agent, by 13%. Nadolol in combination with diuretics and/or pratsiol showed the same effects as did anapriline. The agent possessed a more pronounced negative chronotropic action than did anapriline when it was given alone or in combination. Nadolol caused a decrease in middle and small sized bronchial patency as did anapriline. A 6-month nadolol therapy resulted in regression of left ventricular hypertrophy. PMID- 2202855 TI - [Evaluation of progression and regression of coronary atherosclerosis in long term prospective studies]. PMID- 2202854 TI - [Effects of alcohol on high density lipoproteins]. PMID- 2202856 TI - [The proteolysis system and the nature of morphologic changes of the intestinal wall in acute experimental obstruction]. PMID- 2202857 TI - [Surgical choices in injuries of the inferior vena cava]. AB - The results of treatment of 15 patients with injuries to the inferior vena cava (IVC) are presented. Knife injuries were noted in 13 of them, gunshot injuries- in 1, closed traumas of the thorax and abdomen--in 1. In 6 patients, IVC was injured at its suprarenal part, in 1--at the level of confluence of the renal veins, in 8--at the infrarenal zone. Eight patients died. The peculiarities of therapeutical measures at each step of giving the aid are presented. PMID- 2202859 TI - [Is the development of adhesions after appendectomy related to the methods of stump treatment?]. PMID- 2202858 TI - [Disputable problems in the treatment of acute peptic ulcer hemorrhage]. PMID- 2202860 TI - [Reinfusion of blood in injuries of the digestive organs]. PMID- 2202861 TI - [Indications for relaparotomy and its timing]. PMID- 2202862 TI - [The role of infection in the etiology and pathogenesis of appendicitis, its complications and mortality rates]. PMID- 2202863 TI - [Successful surgical treatment of isolated injury of the superior mesenteric vessels]. PMID- 2202864 TI - [A method of treating the appendiceal stump]. PMID- 2202865 TI - [Leonid Vasil'evich Radevich]. PMID- 2202866 TI - [Role of hemorrheologic disorders in the pathogenesis of oncologic diseases]. PMID- 2202867 TI - [Method of stopping intrapelvic hemorrhage in radical surgery of rectal cancer]. PMID- 2202868 TI - [Kharkov Research Institute of General and Emergency Surgery (on the 60th anniversary of its foundation)]. PMID- 2202869 TI - [Ligation of blood vessels of the root of the lung]. PMID- 2202870 TI - [Splenectomy using a suturing apparatus]. PMID- 2202871 TI - [Diagnosis of disorders of lymph circulation in surgical diseases (review of the literature)]. PMID- 2202872 TI - [Mammary-coronary artery anastomosis in current cardiological surgery]. AB - The article generalizes the experience in the treatment of 193 patients with ischemic heart disease by operation for direct mammary-coronary anastomosis (MCA). The author discusses technical aspects of the operation, in particular the use of vacuum vessel suturing apparatuses for its accomplishment, problems of extracorporeal circulation, and the long-term results. It is concluded that MCA is one of the most effective, reliable, and economical operations and should be used more widely in the management of ischemic heart disease. PMID- 2202873 TI - [Problem of kidney transplantation (on the 25th anniversary of the first successful transplantation of the kidney in the USSR)]. AB - The first successful transplantation of a kidney from an alive relative donor in the USSR was performed by B. V. Petrovsky at the All-Union Research Institute of Clinical and Experimental Surgery (now the All-Union Surgery Research Center, AMS, USSR) on April 15, 1965. In November, 1965 he transplanted a cadaver kidney for the first time with a good outcome. The Center possesses an experience with 987 kidney transplantations to date, among which 101 were related transplantations. The authors discuss the progress made in this field of surgery in a period of 25 years. The longest survival period among recipients with a functioning related kidney is 22 years and among those with a cadaver kidney, 19 years. With the use of Cy A 86% of transplanted related kidneys and 76% of cadaver kidneys function for 12 months or longer. The authors discuss the advantages of a new original method for transorganic oxygen preservation of a kidney suggested by G. A. Asoyan, instrumental-functional methods developed at the Center for appraising the hemodynamics of the transplanted kidney and diagnosis of the rejection crisis, cyclosporine nephrotoxicity, and progress in the techniques of kidney transplantation and immunosuppressive therapy. The authors believe that further improvement in the results of allogeneic kidney transplantation is well-grounded. PMID- 2202874 TI - [Ultrasonic evaluation of regional hemodynamics in arteriosclerosis obliterans of the iliac and femoral arteries]. AB - Regional hemodynamics was studied in 120 patients with atherosclerosis obliterans of the iliac and femoral arteries by ultrasonic Dopplerometry. Regional malleolar systolic pressure, malleolar-upper arm index, and regional systolic perfusion pressure deficit (RSPPD) were determined by an elaborated method. The authors analyse the values of regional hemodynamics according to the severity of the trophic disorders and type of the occlusive lesion of the iliac and femoral arteries. It was established that, being an integral characteristic, RSPPD allows the degree of limb ischemia to be characterized quantitatively most informatively with consideration for the condition of the central hemodynamics. PMID- 2202875 TI - New progress in the four diagnostic methods of cancer. PMID- 2202876 TI - [Rheumatology research. An analysis of the situation in Spain]. AB - To analyze the present status of rheumatological research in Spain, three indicators have been evaluated: use of the different study designs, use of statistical techniques and relevance of the studies. This last point was determined by the comparison of the research areas that had been reported during one year and the lines of rheumatological research established as priorities by 10 investigators from the 10 units of clinical care with a higher scientific output during the period 1985-1987. A revision has been made of the 67 articles from Spain out of the 1106 reported in seven of the journals with a better national and international impact index: Scandinavian Journal of Rheumatology, Arthritis and Rheumatism, Journal of Rheumatology, Annals of the Rheumatic Diseases, British Journal of Rheumatology, Clinical Experimental Rheumatology and Revue du Rhumatisme, in addition to Revista Espanola de Reumatologia. It was found that few studies with analytical design are being published and that complex statistical analysis techniques are not being used; therefore, most articles do not have a possible statistical inference and lack value as predictors. The reports of cases and clinical series in the Letters to the Editor section are most common, particularly in the Spanish journal. Most studies are related with clinical research, although the consulted investigators consider that basic and epidemiological research have a higher priority. It is concluded that the Spanish contribution to the international rheumatological literature is still small and has a mainly descriptive character; thus, it is necessary to emphasize the use of analytical designs to improve the competitiveness. The type of studies to be carried out in the future, according to the priorities established by the investigators themselves, should change if their wishes are to be fulfilled. PMID- 2202877 TI - High-field MRI and US evaluation of the pelvis in women with leiomyomas. AB - Magnetic resonance imaging (MRI) and real-time transabdominal ultrasonography (US) were performed on 23 women with uterine leiomyomas. The uterus, ovaries, and cul de sac were evaluated. Accurate determination of uterine volume was possible in all cases by MRI, but was limited on US in uteri larger than 140 cc. Marked enlargement also prevented visualization of contour abnormalities in eight patients on US, but none on MRI. The endometrial stripe and junctional zone could not be adequately visualized in 21/23 US examinations, whereas they were identified in all 23 MRI (8 normal and 15 distorted). Individual leiomyomas were clearly depicted on 4 US and 19 MR scans, the smallest being 1.1 cm and 0.8 cm, respectively. Of the 31 fibroids present on MRI: 13 were intramural, 4 subserosal, and 14 submucosal. MRI successfully identified 44/46 ovaries as compared to 21/46 on US. Cul de sac fluid was noted in seven women by MRI alone. This data suggests that MRI is superior to US in examination of the entire pelvis in women with leiomyomas. PMID- 2202878 TI - [The hypothesis of season of birth as a risk factor in schizophrenia. Recapitulation and critical review]. AB - The literature on the relationship between season of birth and schizophrenia is reviewed. Analysis of the available data suggests that various factors may be involved in causing the phenomenon. The hypotheses that have been formulated on this epidemiological discovery are analysed and a possible interaction between relational and environmental factors presumably implicated in the explanation of the connection in question is suggested. PMID- 2202879 TI - [Family expressed emotion. From research to therapeutic intervention]. AB - The Expressed Emotion (EE) index is today one of the most important tools to evaluate the effect of family environment on the course of schizophrenia. The A. critically examine many experimental researches, performed on the EE index during the past 15 years, reporting the results of the first Italian replication study. The psychoeducational family interventions (originated by the EE research) are then considered, with particular attention to the treatment conceived by the team of the Association for the Research on Schizophrenia (A.R.S.). In the final section of the paper, the A. propose an extension of the EE research to families with chronic organic pathologies, reporting some preliminary results. PMID- 2202880 TI - T2 of endotoxin lung injury with and without methylprednisolone treatment. AB - NMR relaxation times (T1 and T2) and the water content (WC) of in vitro rat lungs were measured during the course of endotoxin lung injury in rats. Measurements of normal lungs, untreated endotoxin-injured lungs, and endotoxin-injured lungs treated with methylprednisolone (MPSL) were compared. The untreated endotoxin lungs showed prolongation of the fast and slow T2 components (T2f and T2s), but no significant changes in T1 or water content. Also, there was no correlation between 1/WC and relaxation rates or between T1 and T2. MPSL treatment prevented T2f and T2s prolongation; however, the duration of MPSL effectiveness was limited. Animals which were treated with MPSL more than 7 h prior to measurements showed T2 prolongation. This study indicates that NMR relaxation times, particularly T2, can be useful in evaluating lung injuries and their treatments. PMID- 2202881 TI - Visceral fat accumulation in men is positively associated with insulin, glucose, and C-peptide levels, but negatively with testosterone levels. AB - Twenty-three healthy men (age 25 to 50 years), covering a wide range of fatness and body fat distribution, were studied. An oral glucose tolerance test was performed and adipose tissue areas were calculated from computed tomography (CT) scans made at the level of L4/L5. Visceral fat area was associated with elevated concentrations of insulin and C-peptide and with glucose intolerance before and after the oral glucose load. Concentrations of sex-hormone-binding globulin (SHBG), as well as total and free testosterone, were negatively correlated with waist/hip circumference ratio and visceral fat area and also negatively associated with increased glucose, insulin, and C-peptide concentrations. In multiple linear regression, adjusting for age, body mass index, and visceral fat area, serum concentrations of free testosterone were still negatively correlated with glucose, insulin, and C-peptide levels. Without claiming any causality in the observed associations, we conclude that, unlike in women, abdominal fat distribution, insulin, glucose, and C-peptide levels are negatively associated with serum testosterone levels in men. PMID- 2202882 TI - Myocardial metabolism during hypoxia: maintained lactate oxidation during increased glycolysis. AB - In the intact animal, myocardial lactate utilization and oxidation during hypoxia are not well understood. Nine dogs were chronically instrumented with flow probes on the left anterior descending coronary artery and with a coronary sinus sampling catheter. [14C]lactate and [13C]glucose tracers, or [13C]lactate and [14C]glucose were administered to quantitate lactate and glucose oxidation, lactate conversion to glucose, and simultaneous lactate extraction and release. The animals were anesthetized and exposed to 90 minutes of severe hypoxia (PO2 = 25 +/- 4 torr). Hypoxia resulted in significant increases in heart rate, cardiac output and myocardial blood flow, but no significant change in myocardial oxygen consumption. The arterial/coronary sinus differences for glucose and lactate did not change from normoxia to hypoxia; however, the rate of glucose uptake increased significantly due to the increase in myocardial blood flow. Tracer measured lactate extraction did not decrease with hypoxia, despite a 250% increase in lactate release. During hypoxia, 90% +/- 4% of the extracted 14C lactate was accounted for by the appearance of 14CO2 in the coronary sinus, compared with 88% +/- 4% during normoxia. Thus, in addition to the expected increase in glucose uptake and lactate production, we observed an increase in lactate oxidation during hypoxia. PMID- 2202883 TI - Relationships among islet cell antibodies, residual beta-cell function, and metabolic control in patients with insulin-dependent diabetes mellitus of long duration: use of a sensitive C-peptide radioimmunoassay. AB - Relationships among islet cell antibodies (ICA), residual beta-cell function, and metabolic control were studied in 60 insulin-dependent diabetics (IDDs) of long duration (6 to 31 years). Sensitive C-peptide immunoreactivity (CPR) and ICA assays with limits of 0.017 nmol/L and 5 Juvenile Diabetes Foundation (JDF) U, respectively, demonstrated that baseline (0.16 +/- 0.02 nmol/L, mean +/- SE, n = 26), as well as maximum CPR values (0.34 +/- 0.05 nmol/L), during 100-g oral glucose tolerance tests (OGTT) in ICA-positive IDDs were significantly higher than corresponding values in ICA-negative ones (baseline values, 0.10 +/- 0.01 nmol/L, P less than .05; maximum values, 0.20 +/- 0.04 nmol/L, P less than .01, n = 34). Negative correlation was observed between increment of serum CPR and metabolic control indices, including fasting blood glucose (FBG) and HbA1c levels (P less than .05). In addition, ICA-positive insulin-dependent diabetes mellitus (IDDM) patients had lower values of FBG (8.2 +/- 0.4 mmol/L, P less than .01 v ICA-negative IDDs) and HbA1c (9.2% +/- 0.2%, P less than .05 v ICA-negative IDDs) than ICA-negative ones (FBG, 9.9 +/- 0.4 mmol/L; HbA1c, 9.8% +/- 0.2%). These results indicate that minute CPR responses to OGTT detected by sensitive methods may represent residual pancreatic beta cells, which may contribute to ICA generation and good metabolic control in IDDs of long duration. PMID- 2202884 TI - Chronic hyperinsulinemia decreases insulin action but not insulin sensitivity. AB - Hyperinsulinemia and insulin resistance are commonly seen in obese and non insulin-dependent diabetes mellitus (NIDDM) patients, suggesting a causal link exists between hyperinsulinemia and insulin resistance. In a previous study, we demonstrated that chronic (28 days) intraportal hyperinsulinemia (50% increase in basal insulin levels) resulted in a decrease in insulin action as assessed by a one-step euglycemic hyperinsulinemic clamp. Since only one dose of insulin was used during the clamp, it was not possible to determine if the decrease in insulin action was due to a change in insulin sensitivity and/or maximal insulin responsiveness. In the present study, insulin resistance was induced as before, but insulin action was assessed in overnight fasted conscious dogs using a four step euglycemic hyperinsulinemic clamp (1, 2, 10, and 15 mU/kg/min). Insulin responsiveness was assessed before the induction of chronic hyperinsulinemia (day 0), and after 28 days of hyperinsulinemia (day 28). Transhepatic glucose balance and whole-body glucose utilization were measured to allow assessment of both the hepatic and peripheral effects of insulin. Chronic hyperinsulinemia increased basal insulin levels from 13 +/- 2 to 21 +/- 4 microU/mL. After 4 weeks of chronic hyperinsulinemia, maximal insulin-stimulated glucose utilization was decreased 23% +/- 4% (P less than .05) and insulin sensitivity (ED50) was not significantly altered. During the four-step clamp, the liver was a major site of glucose utilization. The liver was responsible for 13% of the total glucose disposal rate on day 0 (2.9 mg/kg/min) at the highest insulin infusion rate (15 mU/kg/min; 2,000 microU/mL).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2202885 TI - Abnormal regulation of intermediary metabolism after oral glucose ingestion in myotonic dystrophy. AB - The responses of plasma insulin and blood intermediary metabolites to oral glucose (75 g) were determined in 10 subjects with myotonic dystrophy. Results were compared with responses in 10 normal control subjects matched for age, sex, and body mass index. Fasting hyperinsulinemia was observed in the myotonic subjects (7.5 +/- 1.6 v 2.4 +/- 0.4 mU/L; P less than .005) and plasma insulin concentration remained significantly higher following oral glucose (F = 38.09; P less than .001). Total cumulative insulin release was markedly higher in the myotonic subjects (4,984.3 v 1,286.6 mU/L; P less than .0001). Basal blood glucose concentration was normal (4.8 +/- 0.2 v 4.7 +/- 0.1 mmol/L), although overall blood glucose was elevated in the myotonic subjects following oral glucose ingestion (F = 5.37; P less than .05). Glucose tolerance was normal in all subjects. Fasting blood lactate was higher in the myotonic subjects (1.31 +/- 0.13 v 0.94 +/- 0.08 mmol/L; P less than .05) and remained significantly elevated following the ingestion of glucose (F = 7.22; P less than .02). Blood pyruvate response was also higher in the myotonic subjects (F = 5.88; P less than .05). Basal blood glycerol was elevated in the myotonic subjects (0.12 +/- 0.02 v 0.05 +/- 0.01 mmol/L; P less than .005) and remained elevated following oral glucose (F = 11.31; P less than .005). No significant overall differences were observed in ketone bodies, alanine, or fatty acids between the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2202886 TI - Metabolic effects of continuous feeding. AB - To study the metabolic effects of slowing absorption, as a possible mechanism for the blood glucose and lipid-lowering effects of soluble fiber and low glycemic index (GI) foods, seven healthy men consumed a liquid formula diet either as three equal meals at 4-hour intervals, or by continuously sipping the same amount of formula over the 12-hour study period. Meal-related fluctuations of blood glucose, insulin, and triglycerides were seen during three meals, but not during sipping. Mean 12-hour levels of blood glucose and beta-hydroxybutyrate (beta OHB) were equivalent on sipping and three meals. The total integrated insulin area was reduced by 32% on sipping (P less than .01), but this was not explained by the 16% (NS) reduction in serum C-peptide response. Mean serum free fatty acid (FFA) and cholesterol levels were reduced by 20% and 2.6%, respectively (P less than .01). It is concluded that the reduced glycemic responses seen after soluble fiber-enriched meals and low GI foods can be explained by slow absorption. Although the overall mean daily blood glucose levels may not be reduced by slowing carbohydrate absorption in nondiabetic subjects, this is achieved at considerably lower ambient serum insulin concentrations. The reduction of insulin levels may be an important mechanism for the serum cholesterol-lowering effect of soluble fiber and low GI foods. PMID- 2202887 TI - Metabolic responses of forearm and adipose tissues to acute ethanol ingestion. AB - Although excess ethanol consumption is often considered to lead to adiposity, the metabolic routes by which this might occur are not clear. We have investigated some metabolic consequences of acute ethanol ingestion by measuring arteriovenous differences across forearm muscle and subcutaneous adipose tissue for 6 hours after ingestion of 47.5 g ethanol, in seven normal subjects fasted overnight. The expected systemic effects of ethanol ingestion were observed: slight lowering of the plasma glucose concentration, depression of plasma nonesterified fatty acid (NEFA) concentrations, and elevation of the blood lactate/pyruvate and 3 hydroxybutyrate/acetoacetate ratios. There was a marked reduction in blood total ketone bodies in relation to plasma NEFA concentrations. However, the only major change observed in peripheral tissue metabolism was an increased uptake of acetate into forearm muscle, equivalent, in whole-body terms, to only 3% of the ethanol load. Adipose tissue appeared to show a reduced cytoplasmic state in that it exported an increased ratio of lactate to pyruvate after ethanol ingestion. However, this reduced state did not lead to increased fatty acid reesterification within adipose tissue. No mechanism was clearly identified whereby ethanol ingestion might lead to net deposition of triacylglycerol in adipose tissue. PMID- 2202888 TI - Elevated lipid peroxidation levels in red blood cells of streptozotocin-treated diabetic rats. AB - This study was performed to determine whether or not hyperglycemia in diabetes results in elevated levels of lipid peroxidation products in red blood cells (RBC). Diabetes was induced in rats by treatment with streptozotocin. The level of lipid peroxidation products was examined in fresh RBC by measuring their thiobarbituric acid (TBA) reactivity after 2 and 4 months of induction of diabetes. Hyperglycemia was assessed by measuring the level of glycosylated hemoglobin and blood glucose. Results show that lipid peroxidation levels were significantly higher (50% to 84%) in RBC of diabetic rats than in controls. The increase in the level of lipid peroxidation was blocked in diabetic rats in which hyperglycemia was controlled by insulin treatment. Among phospholipid classes, relative percentage of sphingomyelin (SM) was significantly reduced in RBC at both 2 and 4 months of diabetes; whereas phosphatidylethanolamine (PE) levels were higher in RBC at 4 months of diabetes only. The level of phosphatidylcholine (PC) did not differ significantly between RBC of control and diabetic rats. This study suggests a significantly altered lipid composition and an accumulation of lipid peroxidation products in RBC of streptozotocin-treated diabetic rats. PMID- 2202889 TI - Thermic effect of a meal over 3 and 6 hours in lean and obese men. AB - Controversy regarding defective postprandial thermogenesis in obesity may partly be due to methodological factors such as duration of measurement. To clarify further the role of blunted thermogenesis in obesity, the thermic effect of food was compared in seven lean (mean +/- SEM, 15.7% +/- 1.5% body fat, by densitometry) and seven obese men (37.3% +/- 3% fat) over 3 and 6 hours. The groups were matched for age (35 +/- 2 and 33 +/- 2 years for the lean and obese groups; range, 25 to 39 years), fat-free mass (FFM), and aerobic fitness. Resting metabolic rate (RMR) was measured by indirect calorimetry for 6 hours on two mornings, in randomized order: (1) after a 720-kcal liquid mixed meal, which was 24% protein, 21% fat, and 55% carbohydrate; and (2) in the postabsorptive state. The thermic effect of food, calculated as postprandial minus postabsorptive RMR, was significantly greater for the lean than obese men for the first 3 hours of measurement (67 +/- 6 v 49 +/- 3 kcal/3 hours; P less than .01). During the second 3 hours, the thermic effect of food was marginally, but not significantly, greater for the lean than obese men (34 +/- 8 v 20 +/- 4 kcal/3 hours; P = .10, NS). Over the entire 6 hours, the thermic effect of food was significantly greater for the lean than obese men (100 +/- 12 v 69 +/- 5 kcal/6 hours; P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2202891 TI - The non-Hodgkin's lymphomas. PMID- 2202890 TI - Inhibitory effect of Ca2+ on formation of Mg2(+)-mediated two-dimensional hexagonal lattice structure by an R-form lipopolysaccharide from Klebsiella pneumoniae. AB - When the R-form lipopolysaccharide (LPS) from Klebsiella pneumoniae strain LEN 111 (O3-:K1-), from which cationic material had been removed by electrodialysis, was suspended in 50 mM Tris buffer at pH 8.5 containing 0.1 mM or higher concentrations of MgCl2, it formed an ordered two-dimensional hexagonal lattice structure and its center-to-center distance (lattice constant) depended upon the concentration of MgCl2 and reached the shortest value (14 nm) at 10 mM. In contrast, in the presence of 0.1 to 10 mM CaCl2 in place of MgCl2, the electrodialyzed LPS did not form such an ordered hexagonal lattice structure but formed an irregular network structure with a center-to-center distance of 19 to 20 nm. We investigated interaction of Mg2+ and Ca2+ in formation of the hexagonal lattice structure by the electrodialyzed LPS suspended in 50 mM Tris buffer at pH 8.5. When 0.1 mM or higher concentrations of CaCl2 were mixed with 1 mM MgCl2 or when 1 mM or higher concentrations of CaCl2 was mixed with 10 mM MgCl2, the electrodialyzed LPS did not form the hexagonal lattice structure of the magnesium salt type but formed the irregular network structure of the calcium salt type. In the coexistence of equimolar or higher concentrations of CaCl2 together with 1 or 10 mM MgCl2, the binding of Mg to the electrodialyzed LPS was significantly inhibited and, conversely, the binding of Ca was enhanced as compared with when MgCl2 or CaCl2 was present alone. However, the coexistence of 10 times less molar concentrations of CaCl2 did not significantly inhibit the binding of Mg to the electrodialyzed LPS. Therefore, the inhibition of formation of the Mg2(+) mediated hexagonal lattice structure of the electrodialyzed LPS by equimolar or higher concentrations of CaCl2 accompanied the inhibition of binding of Mg but that by 10 times less molar concentrations of CaCl2 did not accompany it. PMID- 2202892 TI - Interleukin-2. PMID- 2202893 TI - 'CO-CO' in nursing care planning: an innovative approach to student learning. AB - This qualitative study evaluated the application of a new real-time, synchronous computer conferencing technology (CO-CO) to assist student nurses develop effective nursing care planning skills. Using CO-CO, first-year undergraduate nurses collaborated across a local area network to produce nursing care plans based on given patient profiles. A convenience sample involved a total of eight students, working in pairs at different work stations. An initial training session introduced the students to the Unisys Icon microcomputer system and the CO-CO software application. In the second session the researcher displayed a patient case study in one of the CO-CO screen windows along with specific instructions. The students' objective was to co-operate and collaborate as a group in order to produce an appropriate nursing care plan. For the most part they worked independently of the teacher who was able to engage in other activities while remaining available to the group for occasional essential feedback. Later, a questionnaire was completed by the students. The students cited the ease with which they could use the software CO-CO to reach decisions about care. The sessions reportedly improved group process and group interaction. This computer conferencing system offers an alternative approach to the teaching of nursing care planning. PMID- 2202894 TI - Drug calculations for nurses--a computer assisted learning application. AB - A summative evaluation of the effectiveness of a computer assisted learning package, 'Drug Calculations for Nurses' was conducted. Two groups of students, the experimental and control were chosen from the schools of nursing where English was used as the medium of instruction. The experimental group was taught drug calculations in classrooms, but not the control group. Both groups used the software after they had attempted a drug calculation test. A post-treatment test of similar nature was undertaken to reflect the students' mathematical achievement. An attitude semantic differential was used to measure subjects' attitude. Findings of this investigation indicated that there was a significant difference in mathematical achievement of the students who experienced both teaching strategies as compared with the group taught by the computer software only. The experimental group scored significantly higher in their post-treatment test. Even though the control group did show some improvement, it was not statistically significant. Both groups demonstrated a positive attitude towards computer assisted learning, however, only the mean scores for the subscales comfort and function were significant. Implications of this study were then identified and areas for future research were recommended. PMID- 2202895 TI - Noise and hearing loss. AB - The National Institutes of Health Consensus Development Conference on Noise and Hearing Loss brought together biomedical and behavioral scientists, health care providers, and the public to address the characteristics of noise-induced hearing loss, acoustic parameters of hazardous noise exposure, individual and age specific susceptibility, and prevention strategies. Following a day and a half of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared a consensus statement. Among their findings, the panel concluded that sounds of sufficient intensity and duration will damage the ear and result in temporary or permanent hearing loss at any age. Sound levels of less than 75 dB(A) are unlikely to cause permanent hearing loss, while sound levels above 85 dB(A) with exposures of 8 hours per day will produce permanent hearing loss after many years. Current scientific knowledge is inadequate to predict that any particular individual will be safe when exposed to a hazardous noise. Strategies to prevent damage from sound exposure should include the use of individual hearing protection devices, education programs beginning with school-age children, consumer guidance, increased product noise labeling, and hearing conservation programs for occupational settings. The full text of consensus panel's statement follows. PMID- 2202896 TI - Comparative genotoxicity testing of mainstream whole smoke from cigarettes which burn or heat tobacco. AB - The genotoxic potential of mainstream whole smoke (MWS) from cigarettes which heat tobacco (TEST) was compared to the genotoxic potential of MWS from a cigarette which burns tobacco (REFERENCE). MWS was collected from a University of Kentucky 1R4F cigarette (REFERENCE) and two, TEST cigarettes, one with regular flavor and the other with menthol flavor. All cigarettes were smoked on a smoking machine and the particulate phase was collected on Cambridge filter pads. The vapor phase, which passed through the pad, was bubbled into a dimethyl sulfoxide (DMSO) trap. The filter pad was extracted with the DMSO in the trap and additional DMSO to obtain MWS. MWS representing an identical number of cigarettes was tested to make a per-cigarette comparison of their genotoxic potential. REFERENCE MWS was mutagenic and cytotoxic in the Ames assay in the presence of metabolic activation while it was cytotoxic but not mutagenic in the absence of metabolic activation. Statistically significant increases in frequency of both sister-chromatid exchanges and chromosomal aberrations were observed in Chinese hamster ovary cells exposed to REFERENCE MWS with and without metabolic activation. MWS from the TEST cigarettes, with either regular or menthol flavor, was neither cytotoxic nor mutagenic in any of these assays. In summary, MWS from the 2 TEST cigarettes was neither genotoxic nor cytotoxic under conditions where MWS from the REFERENCE cigarettes was genotoxic and/or cytotoxic in a concentration-dependent manner. PMID- 2202897 TI - Mutagenic compounds in wood-chip drying fumes. AB - The mutagenicity of fumes from the heating of freshly cut spruce and birch chips was measured with Salmonella typhimurium strains TA98, TA100 and TA102. The bacteria were exposed directly and indirectly to the fumes. Wood chips were also extracted with solvents. No mutagenicity was found in wood extracts or the fume samples measured indirectly. The results from the direct exposure experiments indicate, however, that drying spruce and birch at 170 degrees C emits mutagenic compounds, which are short-lived and/or volatile. One of the mutagenic compounds of the fumes is probably 3-carene. These results are consistent with previous epidemiological findings, which suggest that these fumes are carcinogenic. PMID- 2202898 TI - Nitro reaction in mice injected with pyrene during exposure to nitrogen dioxide. AB - We have previously reported that the beta-glucuronidase-treated urine of mice injected intraperitoneally with pyrene during exposure to NO2 contained highly mutagenic compounds such as nitropyrene metabolites when tested by the Ames assay using Salmonella typhimurium strain TA98. In the present study, we found that the formation of these mutagens was dose-dependent between 10 and 200 mg of pyrene per kg of body weight at 5 and 10 ppm of NO2. Further, to elucidate the substrate of nitration in vivo, we injected 1-hydroxypyrene, which is the metabolite of pyrene, to mice intraperitoneally during exposure to NO2. Since the results were the same as those obtained by injection with pyrene, we suggest that the pyrene was not nitrated directly but after its hydroxylation. PMID- 2202899 TI - The mutagenic modulating effect of p-phenylenediamine on the oxidation of o- or m phenylenediamine with hydrogen peroxide in the Salmonella test. AB - The mutagenicity of o- and m-phenylenediamine (PD) was remarkedly enhanced by oxidation; their major mutagenic oxidation products were 2,3- and 2,7 diaminophenazine, respectively. In order to evaluate the modulation effect of p PD on the oxidation of m- or o-PD, p-PD and mixtures of m- and p-PD (m-PD/p-PD) and o- and p-PD (o-PD/p-PD) were oxidized with hydrogen peroxide and their mutagenicity was tested in Salmonella typhimurium TA98 in the presence or absence of a mammalian metabolic activation system (S9 mix). The H2O2-oxidized m-PD/p-PD and o-PD/p-PD were potent mutagens with S9 mix, whereas H2O2-oxidized p-PD was slightly mutagenic. The major mutagenic oxidation products of m-PD/p-PD and o PD/p-PD were identified as 2,7- and 2,3-diaminophenazine, respectively, by TLC and HPLC. 2,8-Diaminophenazine was also found as a reaction product in oxidized m PD/p-PD, and it was weakly mutagenic. The mutagenic potency of oxidized m-PD/p-PD or o-PD/p-PD was lower than that of singly oxidized m-PD or o-PD. The yield of 2,7- and 2,3-diaminophenazine was obviously decreased with increases in p-PD, and it was concluded that the declined mutagenic potency of oxidized m-PD/p-PD or o PD/p-PD was due to the decrease in diaminophenazines. But the formation of diaminophenazines was not completely inhibited by the addition of a 9-fold molar ratio of p-PD to m-PD or o-PD, 8.6 nmole of 2,7-diaminophenazine and 1882.4 nmole of 2,3-diaminophenazine were formed from 1 mmole of m-PD and o-PD, respectively. PMID- 2202900 TI - Direct-acting mutagenic properties of some hair dyes used in New Zealand. AB - Mutagenicity or carcinogenicity data are not publicly available on many hair dyes or dye components commonly used within New Zealand. Representative mid- to dark warm brown hair dyes of 12 brands supplying more than 1% of the New Zealand market were tested for direct-acting mutagenicity using the bacterial 'Ames' test. Despite recent scientific advances in the development of non-mutagenic dyes, 23 of the 40 products tested gave positive results in one or both of the tester strains used. There appeared to be differences between distributors in the proportion of their hair dyes which were mutagenic. In the case of 6 out of 10 of the above dyes which had tested positive, in vitro mutagenicity or toxicity was enhanced in the presence of verapamil, suggesting that risks from hair-dye exposure may change in the case of persons using this or similar drugs. It is recognised that there are uncertainties regarding human risks from dyes which are shown to be mutagenic in in vitro tests. However, from the above results, it seems possible to produce non-mutagenic hair dyes in this color range; and in the interests of public reassurance, it may be prudent to require that such dyes be used. PMID- 2202901 TI - A clinical trial of beta carotene to prevent basal-cell and squamous-cell cancers of the skin. The Skin Cancer Prevention Study Group. AB - BACKGROUND: Beta carotene has been associated with a decreased risk of human cancer in many studies employing dietary questionnaires or blood measurements, and it has had protective effects in some animal models of carcinogenesis. METHODS: We tested the possible cancer-preventing effects of beta carotene by randomly assigning 1805 patients who had had a recent nonmelanoma skin cancer to receive either 50 mg of beta carotene or placebo per day and by conducting annual skin examinations to determine the occurrence of new nonmelanoma skin cancer. RESULTS: Adherence to the prescribed treatment was good, and after one year the actively treated group's median plasma beta carotene level (3021 nmol per liter) was much higher than that of the control group (354 nmol per liter). After five years of follow-up, however, there was no difference between the groups in the rate of occurrence of the first new nonmelanoma skin cancer (relative rate, 1.05; 95 percent confidence interval, 0.91 to 1.22). In subgroup analyses, active treatment showed no efficacy either in the patients whose initial plasma beta carotene level was in the lowest quartile or in those who currently smoked. There was also no significant difference between treated and control groups in the mean number of new nonmelanoma skin cancers per patient-year. CONCLUSIONS: In persons with a previous nonmelanoma skin cancer, treatment with beta carotene does not reduce the occurrence of new skin cancers over a five-year period of treatment and observation. PMID- 2202904 TI - Genetics. If it smells like a unicorn... PMID- 2202905 TI - Streptomycin and self-splicing. PMID- 2202903 TI - Coming of age--the chemoprevention of cancer. PMID- 2202902 TI - Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. AB - BACKGROUND: Patients with head-and-neck cancers who are free of disease after local therapy remain at high risk for both recurrent and second primary tumors. Retinoids have proved efficacious in the treatment of premalignant oral lesions and are promising agents for the prevention of epithelial carcinogenesis. METHODS: We prospectively studied 103 patients who were disease-free after primary treatment for squamous-cell cancers of the larynx, pharynx, or oral cavity. After completion of surgery or radiotherapy (or both), these patients were randomly assigned to receive either isotretinoin (13-cis-retinoic acid) (50 to 100 mg per square meter of body-surface area per day) or placebo, to be taken daily for 12 months. RESULTS: There were no significant differences between the two groups in the number of local, regional, or distant recurrences of the primary cancers. However, the isotretinoin group had significantly fewer second primary tumors. After a median follow-up of 32 months, only 2 patients (4 percent) in the isotretinoin group had second primary tumors, as compared with 12 (24 percent) in the placebo group (P = 0.005). Multiple second primary tumors occurred in four patients, all of whom were in the placebo group. Of the 14 second cancers, 13 (93 percent) occurred in the head and neck, esophagus, or lung. CONCLUSIONS: Daily treatment with high doses of isotretinoin is effective in preventing second primary tumors in patients who have been treated for squamous-cell carcinoma of the head and neck, although it does not prevent recurrences of the original tumor. PMID- 2202906 TI - Kaposi's sarcoma and AIDS. PMID- 2202907 TI - Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development. AB - The int-1 proto-oncogene was first identified as a gene activated in virally induced mouse mammary tumours. Expression studies, however, suggest that the normal function of this gene may be in spermatogenesis and in the development of the central nervous system. Genes sharing sequence similarity with int-1 have been found throughout the animal kingdom. For example, int-1 has 54% amino-acid identity to the Drosophila segment polarity gene wingless (wg). Both the int-1 and wg gene products seem to be secreted proteins, presumably involved in cell cell signalling. We have now explored the function of int-1 in the mouse by disrupting one of the two int-1 alleles in mouse embryo-derived stem cells using positive-negative selection. This cell line was used to generate a chimaeric mouse that transmitted the mutant allele to its progeny. Mice heterozygous for the int-1 null mutation are normal and fertile, whereas mice homozygous for the mutation may exhibit a range of phenotypes from death before birth to survival with severe ataxia. The latter pathology in mice and humans is often associated with defects in the cerebellum. Examination of int-1-/int-1- mice at several stages of embryogenesis revealed severe abnormalities in the development of the mesencephalon and metencephalon indicating a prominent role for the int-1 protein is in the induction of the mesencephalon and cerebellum. PMID- 2202908 TI - [Diagnosis and treatment of chronic polymorph light dermatoses]. PMID- 2202909 TI - [Bavaroise and an epidemic of Salmonella enteritidis]. PMID- 2202910 TI - [Tuberous sclerosis]. PMID- 2202911 TI - [Evaluation of clinical-pathological conferences using a program for computer assisted diagnosis; analysis of 100 case reports]. AB - Case studies as weekly published in the New England Journal of Medicine are analysed using the computer programme Medwise. The programme covers more than 3,500 disease profiles. After entering clinical data on all patients described in 1986 and 1987, the diagnostic outcome was compared with the results of the clinicians and with the eventual patho-anatomical findings. Medwise gave the correct diagnosis in 93% of the 104 cases considered. In 15 cases the clinicians failed to formulate the patho-anatomical diagnosis; Medwise correctly detected nine of these (60%). Medwise missed the diagnosis in seven cases, but the clinicians' answers were also faulty in six of them. These results indicate the usefulness of computer-assisted interpretation of clinical findings for establishing the diagnosis, provided that the course and laboratory data concerning the patient are accurately documented. PMID- 2202912 TI - [Chronic fatigue syndrome--a new disease picture?]. AB - The chronic fatigue syndrome has recently been more frequently diagnosed. Yet it is unknown if this syndrome represents a disease entity of its own or merely a diagnostic label for a miscellaneous group of disorders. Further investigations are needed to find out if the syndrome has an organic or psychosomatic aetiology, or a mixture of both. In the meantime it is the responsibility of the clinician to make this decision in each individual case. PMID- 2202913 TI - [Max Weber's importance for the concept of understanding in psychiatry]. PMID- 2202914 TI - [Subjective aspects of psychopathologic research. A method for assessing anxiety in melancholic patients]. AB - Psychopathological assessment of anxiety is subject to considerable methodological problems. An immediate access to an understanding of anxiety is not possible. Rather, anxiety reveals itself to the investigator from the patients' experience, as it comes to light in their self-reports, i.e. from a subjective aspect. Based on these considerations, a semistructured clinical interview was developed for recording anxiety in endogenous depression (syn. melancholia). The decision not to employ a highly structured interview procedure is substantiated by clinical examples. Nevertheless the rules of psychopathometry can be applied to the interview. With the reliability-validity dilemma in mind, the method of psychopathological research proposed occupies an intermediate position between descriptive-phenomenological and "quantitative" psychopathology. PMID- 2202915 TI - [Alcoholism as a disease (C. v. Brhl-Cramer)]. PMID- 2202916 TI - [Excessive gambling as a disease? Critical remarks on inflation of dependencies]. PMID- 2202917 TI - Liver transplantation: a challenge to nephrologists. PMID- 2202918 TI - Renal elimination of beta-2-microglobulin and myoglobin in patients with normal and impaired renal function. AB - Since the demonstration that beta 2-microglobulin (beta 2M) is an amyloidogenic protein in man, the excretion of this low-molecular-weight protein under conditions with normal and reduced renal function has received increased interest. The renal arteriovenous extraction of beta 2M, polyfructosan (an inulin analogue), and a second low-molecular-weight protein, myoglobin, was measured in vivo in 16 human kidneys with normal renal function/gross morphology and in 22 kidneys with reduced function. In kidneys with normal function, the extraction of beta 2M significantly exceeded that of polyfructosan (0.198 +/- 0.037 vs. 0.182 +/- 0.05; p = 0.04), while that of myoglobin (0.177 +/- 0.068) was not different from that of polyfructosan. In kidneys with reduced function, the extraction of polyfructosan or myoglobin was not significantly altered. In contrast, the beta 2M extraction decreased to 0.110 +/- 0.060 (p less than 0.01 vs. extraction of polyfructosan or myoglobin). This decrease was significantly correlated with the decrease of the endogenous creatinine clearance or the total or unilateral 131I hippuran clearance. These results indicate that in normal renal function the glomerular filtration of beta 2M may be supplemented by a peritubular mode of removal. The mechanism(s) underlying the selective decrease of beta 2M extraction in kidneys with reduced function remain speculative. However, this decrease will lead to a further augmentation of the retention of beta 2M in renal failure. PMID- 2202919 TI - Dialyzable factors from uremic serum increase 125I-fibrinogen binding by normal blood platelets. AB - The influence of uremic serum on 125I-fibrinogen binding by normal blood platelets after induction with adenosine diphosphate was evaluated. The study was performed on 12 hemodialyzed uremic patients. The control group included 12 healthy subjects. It has been demonstrated that the uremic serum from the patients before hemodialysis significantly augmented fibrinogen binding by normal blood platelets (33.8 +/- 11.8%) in comparison with control subjects (14.4 +/- 8.9%). After hemodialysis, fibrinogen binding was comparable with the control group (14.9 +/- 10.1%). Uremic toxins removable during hemodialysis are probably responsible for the potentiation of 125I-fibrinogen binding by platelets. PMID- 2202920 TI - Low dose ciclosporin from the early postoperative period yields potent immunosuppression after renal transplantation. AB - This study sought to determine if low doses of ciclosporin (CS) designed to give fasting serum levels of 50-100 ng/ml achieve effective immunosuppression when used from the early postoperative period after renal transplantation. Ninety-four primary renal transplant recipients were studied. Group 1 patients were treated with CS 100 ng/ml and prednisone (0.15 mg/kg/day). Group 2 patients received CS 50 ng/ml, prednisone (0.15 mg/kg/day) and azathioprine (1 mg/kg/day). These patients were compared to a control group of 26 patients (group 3) maintained on only prednisone and azathioprine. CS-treated patients suffered significantly fewer rejection episodes than control subjects (rejection episodes per patient in first year: group 1: 0.3 +/- SD 0.6; group 2: 0.7 +/- SD 0.7; group 3: 1.3 +/- SD 1.1, p less than 0.005). In addition, a greater number of CS-treated patients were completely free of rejection episodes during the first year posttransplant (group 1: 63%; group 2: 64%; group 3: 19%, p less than 0.005). Patient and graft survival were similar in all groups after 1 year (group 1: 92 and 92% respectively; group 2: 95 and 87% respectively; group 3: 96 and 85% respectively). These data suggest that the dose of CS required for effective immunosuppression in vivo is lower than has been previously thought. PMID- 2202921 TI - Comparison of urinary tract infection in calcium oxalate and calcium phosphate stone formers. AB - To compare the frequency of urine infection in calcium oxalate and calcium phosphate stone formers, we reviewed charts from patients whose last renal stone submitted for analysis was predominantly composed of calcium phosphate in 118 and of calcium oxalate in 223. Positive cultures were commoner, but not significantly, in the phosphate than the oxalate stone formers, both in men (17 vs. 7.6%) and women (22 vs. 15%). Bacteria frequently producing urease were found in only 4% of the phosphate group. Urine leucocytes were slightly more frequent in the oxalate group for men and significantly so for women. The results do not support the concept that calcium phosphate stones are mainly due to infection with urease-producing or other bacteria. PMID- 2202922 TI - Calculus in 16-year-old cadaveric kidney transplant: a unique case and literature review. AB - Calculi are rare in transplanted kidneys with an incidence of 0.1-0.2% of all urological complications. The clinical presentation of an obstructing stone is different from that seen in nontransplant patients and can be easily mistaken for rejection. Ultrasonography and renogram may fail to detect it. Steroid therapy, the treatment of choice for acute rejection, may improve renal functions albeit obstruction. An obstruction ureteral stone in a 16-year-old cadaveric kidney transplant was mistaken for acute rejection. Steroid therapy improved renal function for a short time, but then anuria recurred. Failing treatment, the kidney was considered lost and hemodialysis was started. Spontaneous passage of a stone and improved renal functions clarified the picture. The literature regarding kidney transplant stones is reviewed. PMID- 2202924 TI - [Fetal and maternal risk of pregnancy in women with primary chronic glomerulonephritis]. AB - This review focuses on the reciprocal influence of underlying primary glomerular disease on fetal outcome and of pregnancy on the course of maternal nephropathy, based on most recent data in the literature and on a personal series of 240 pregnancies in 122 women with biopsy-proven chronic glomerulonephritis (CGN) followed at Necker Hospital. The first part analyzes the fetal outcome in the various histopathologic types of CGN and points out the major influence as risk factors for fetal outcome, of the presence of nephrotic syndrome, high blood pressure and/or impaired renal function at conception. The second part deals with the debated problem of the influence of pregnancy on maternal renal disease. It has become evident that pregnancy has no deleterious effect per se on the course of maternal disease when renal function is normal or near normal at conception, whereas an accelerated course is often observed when plasma creatinine is in excess of 0.18 mmol/l at conception, whatever the type of CGN. In the third part are described preconception counselling and the practical rules of maternal and fetal surveillance. PMID- 2202923 TI - Fish oil to prevent intimal hyperplasia and access thrombosis. PMID- 2202925 TI - Assessment: the clinical usefulness of botulinum toxin-A in treating neurologic disorders. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. PMID- 2202926 TI - Cerebral blood flow velocity alterations during obstructive sleep apnea syndrome. AB - We recorded cerebral blood flow velocity (CBFV) for the assessment of CO2 regulated alterations during apnea by means of transcranial Doppler ultrasound in a patient with obstructive sleep apnea syndrome. CBFV increased up to doubled peak flow values during obstructive apneic phases. The results provide evidence for a normal CO2 regulation of CBFV leading to periodic vascular stress during the night. PMID- 2202927 TI - Effect of clomipramine on myotonia: a placebo-controlled, double-blind, crossover trial. PMID- 2202928 TI - Transcranial Doppler in brain death. PMID- 2202929 TI - [Early gastric cancer: radiologic, endoscopic or combined diagnosis?]. AB - Having underlined the importance of an extremely early diagnosis of gastric cancer, the paper focuses on the diagnostic capacities of endoscopy and bone x ray using a dual-contrast technique. From an analysis of published reports and on the basis of their own experience, the authors prefer, whenever possible, to combine the two methods, since this is the only way of revealing minimum neoplastic stomach lesions in almost 100% of cases. PMID- 2202930 TI - [A frequent complication of enterostomy: prolapse]. AB - Among the other complications of enterostomy, prolapse deserves particular mention on account of the therapeutic problems involved in its correction. Based on a report of the authors' personal experience, the paper focuses on the mechanisms of onset and, above all, on the most appropriate forms of treatment, before continuing to describe the different surgical reparative techniques. In conclusion, the authors affirm that an optimal tailoring of the enterostomy and its appropriate preparation represent the ideal method of preventing the onset of prolapse. PMID- 2202931 TI - [Tumors of the anus]. AB - On the basis of an analysis of a personal series of anal tumours, it is concluded that the polychemotherapeutic protocol with mitomycin and 5-fluorouracil and extensive local tumour removal proposed by Nigro et al. could present a valid alternative to Miles anorectal amputation. The treatment proposed offers better quality of life for the patient without changing oncological radicality and survival. PMID- 2202932 TI - [The use of a topical antibacterial agent (silver sulfadiazine) on soft-tissue wounds]. AB - Reducing the quantitative level of bacterial contamination in an open, acute or chronic, soft tissue wound below the critical level of 10(5) bacteria per gram of viable tissue is essential to delayed primary closure. First step in the management of the contaminated or infected wound is accurate local debridement, preferably with pulsating jet irrigation. Topical antibacterial agents, specifically silver sulfadiazine cream, are then usefully employed to reduce the bacterial count. Contrary to systemic antibiotics, these agents penetrate adequately into the open, granulating wound with a direct bacteriostatic or bactericidal action on a wide spectrum of gram positive and negative organisms, without the effect of local tissue injury typical of topical antiseptics. The use of topical antibacterials, traditionally confined to the treatment of the burn wound, the open "difficult" wound for excellence where control of local infection is first priority, provides a rapid local reduction of the bacterial level and paves the way to the final goal of primary delayed closure of the wound, either direct or with the use of grafts or local, distant, or free flaps. PMID- 2202933 TI - [Aneurysm of the splenic artery. A clinical case and review of the literature]. AB - The Authors report a case of splenic artery aneurysm (ASA) in a 64 years old woman. Most of patients affected by ASA are asymptomatic. Rupture represents a rare complication with high mortality rate. Finally the clinical, etiopathogenetic and anatomo-pathological aspects are considered. PMID- 2202934 TI - [Lesions of the colon caused by pancreatitis]. AB - A case of stenosis of the splenic flexure of the colon consequent on acute pancreatitis is reported. Literature reports on the colic complications of pancreatitis are examined, analysing the pathogenetic mechanisms, clinical pictures and therapeutic problems involved in this pathology. PMID- 2202935 TI - The removable orthopedic/orthodontic approach. An overview. PMID- 2202936 TI - Iconodontalgia IV. PMID- 2202937 TI - Is periodontal disease during orthodontics preventable? AB - Periodontal disease during orthodontic therapy is preventable and is controllable and in continuous studies after orthodontic therapy has been completed, it has been shown that under the properly controlled regimen of treatment the destruction to the periodontal tissues of the teeth is not accentuated to a statistically significant degree as greater than that which occurs during the same interim without orthodontic therapy. This encourages us; however, the difficulties cited in the paper above challenges us and our finest professional skills in the proper care of the orthodontic patients with periodontal complications. PMID- 2202938 TI - The prediction of facial aesthetics. PMID- 2202939 TI - Weighing the good and the bad in medicine. PMID- 2202940 TI - [Suture of the meniscus in acute instability of the knee joint]. AB - The authors describe a multiform function of the menisci and the causes of frequently occurring simultaneous injuries of the meniscus and of the ligament. In 26 cases of acute instability of the knee the authors put sutures over the meniscus. In all the cases the results were good, there were no complications and there was no need to make a repeated operation in any of the cases. Making use of the suture over the meniscus, it is possible to improve the results of the surgical treatment of instability of the knee to a greater extent. PMID- 2202941 TI - [History of the SICOT (Societe' Internationale de Chirurgie Orthopedique)]. PMID- 2202942 TI - [50th anniversary of the Polymer Laboratory of the CITO (Central Institute of Traumatology and Orthopedics)]. PMID- 2202944 TI - Chemical evolution and the origin of life. Bibliography supplement 1986. PMID- 2202943 TI - [Reflexotherapy in orthopedics, traumatology and prosthetics (review of the literature)]. PMID- 2202945 TI - [Screening for diabetes in obese pregnant women]. AB - Oral glucose tolerance testing (oGTT) was performed according to WHO criteria among obese pregnant women (body mass index greater than 28) who were recruited with the help of computerized pregnancy counselling data base. oGTT was carried out for the first time between gestational ages of 16-20 weeks, and it was repeated monthly as far as possible. Gestational diabetes was diagnosed in 4 cases out of 50 obese patients. Two gestational diabetic patients needed insulin treatment. According to computerized data obese patients have significantly higher risk of having macrosomic infants and/or intrauterine death. Fasting blood glucose values of obese pregnant women were significantly higher in all the gestational ages. It is emphasized that obesity means a risk factor for gestational diabetes, but the onset of carbohydrate intolerance may be prevented or diagnosed as early as possible with the help of repeated oGTT during pregnancy and dietary counselling. In this way fetal complications, especially macrosomia will not develop. PMID- 2202946 TI - [Penetrating injury of the rectum and common iliac artery]. AB - The author reports on an unusual form of a spitting accident when rectum perforation was associated with a arteria iliaca injury laceration. First the artery was reconstructed, then the wound of the rectum was sewn. After this a two tube diverting temporary anus sigmoideus was made. The author emphasises that in artery operations in a septic area one should try to use the patient's own vein and to avoid implanting an artificial prosthesis. Besides an antibiotic treatment great importance is attributed to a temporary complete disconnection of the injured section of intestine. PMID- 2202947 TI - Identification of protein complexes containing the c-rel proto-oncogene product in avian hematopoietic cells. AB - The c-rel proto-oncogene product has been identified as a 75 kDa protein expressed in lymphoid cells transformed by REV-T and Marek's disease virus. A 4.0 kb c-rel transcript is expressed in the bursa, spleen and thymus of chickens with highest levels of expression at 10 days post hatch. Using antiserum specific for the v-rel oncogene product, P75c-rel has been precipitated from [35S]methionine labeled extracts of bursal, splenic and thymic lymphocytes. Additionally, proteins with the molecular mass of 40 kDa, 115 kDa, and 124 kDa co immunoprecipitate. These proteins co-migrate with the proteins found associated with pp59v-rel in REV-T transformed lymphoid cells. Antiserum specific for pp40, the most abundant cellular protein associated with pp59v-rel, co-precipitates p75c-rel verifying the existence of p75c-rel/pp40 complexes in normal avian lymphocytes. Antiserum directed against the amino-terminal region of pp59v-rel fails to precipitate native p75c-rel complexes from normal lymphoid cells. In the presence of ionic detergents, antisera directed against the amino, middle and carboxy-regions precipitate equivalent amounts of p75v-rel. These results suggest that the amino-terminal region of p75c-rel is active in binding other proteins or is inaccessible to the antiserum due to the conformation of p75c-rel in the complex. Two p75c-rel complexes exist in the cytosol of normal lymphocytes. The most abundant complex contains 60% of the p75c-rel associated with p115 and p124. The remaining p75c-rel is associated with pp40. PMID- 2202948 TI - Alternative splicing of the human c-myb gene. AB - Two cDNA clones of the human c-myb gene have been isolated from a CCRF-CEM leukemia cell cDNA library and sequenced in their entirety. These sequences, when compared with those previously reported for the human c-myb gene, reveal an alternative splicing process that generates at least four forms of the c-myb message. Three of these forms co-migrate on Northern blots and are co-expressed in several human hematopoietic cell types. Data on sequence comparisons with mouse and chicken homologues of c-myb coupled with oligonucleotide hybridization to genomic clones of the human c-myb gene indicate that this alternative splicing process utilizes three closely spaced splice donor sites and two unique exons present between viral defined exons 5 and 6. In one clone, the alternative splicing would generate a predicted myb protein with a three amino acid deletion in the region involved in transcription activation. In the other clone, incorporation of a new exon leads to introduction of a translation stop codon leading to loss of the entire carboxy terminus of the protein. This includes loss of a portion of the region involved in transcription activation as well as a separate highly conserved domain. The effect of these changes on protein function is currently unknown. PMID- 2202949 TI - Characterization of monoclonal antibodies specific to the activated ras p21 with aspartic acid at position 13. AB - The ras proto-oncogenes encode membrane bound proteins (p21) which are structurally distinct from the proteins encoded by the activated transforming ras genes. These activated ras genes have been identified in various human tumors as well as their preneoplastic lesions such as colorectal tumors (20-40%), pancreatic carcinomas (95%), lung carcinomas (20-30%), myelodysplasia (40%) and acute myeloid leukemia (30%). The activation of ras p21 is due to amino acid substitutions at positions 12, 13 or 61 of the p21 protein. This report describes two monoclonal antibodies designated D129 and D146 raised against a synthetic peptide corresponding to amino acids 5-16 of ras p21 activated by the substitution of aspartic acid for glycine at position 13. D129 and D146 react specifically with the peptide with the aspartic acid substitution at position 13, but not with the peptide with valine at position 13 or the peptide containing the normal glycine at position 13. Western blot analysis demonstrates that D129 and D146 react specifically with p21 extracted from transformed NIH3T3 fibroblast lines containing aspartic acid at position 13. These studies also demonstrate that D146 is able to detect the activated p21 with aspartic acid at position 13 that is shed into the culture media. Studies demonstrate that MAb D146 specifically immunoprecipitates the cellular p21 with aspartic acid at position 13 from transformed NIH3T3 cells, whereas D129 cannot immunoprecipitate the activated p21. Using a sandwich ELISA format, D146 is able to detect the p21 with position 13 aspartic acid from cell extracts and culture fluids. The ability of D146 to function in the ELISA format raises the possibility that this assay maybe a quick and effective way of determining the presence of activated p21 with aspartic acid at position 13 in human fluids and tissues. PMID- 2202950 TI - Isolation of a new class of 'flat' revertants from ras-transformed NIH3T3 cells using cis-4-hydroxy-L-proline. AB - A new class of nontransformed revertant cells has been isolated from the ras transformed cell line DT using cis-4-hydroxy-L-proline (CHP) as a selective agent. The new revertants, CHP 9CJ and CHP CB4, each contain two copies of the v Ki-ras gene, elevated levels of phosphorylated p21ras protein, and rescuable transforming virus, indicating that the revertant phenotype observed in these cells does not result from inactivation of v-Ki-ras or inhibition of its expression. Both CHP 9CJ and CHP CB4 revertants show a greatly reduced ability to form colonies in soft agar and to produce tumors in syngeneic mice. CHP 9CJ cells are resistant to retransformation by ras and by additional oncogenes that do not encode tyrosine kinases. A comparison of oncogene resistance patterns in these CHP-derived revertants with those from our original ouabain-derived revertants fos C-11 and F-2 indicates that oncogenes may be divided into four general groups. Oncogenes that encode proteins structurally related to p21ras comprise the first group. The second group contains only tyrosine kinase-encoding oncogenes. The third group is composed of 'nuclear', e.g. fos, and 'cytoplasmic' serine-threonine-encoding oncogenes such as mos and raf. The fourth group contains the oncogenes sis and fms. PMID- 2202951 TI - Most tumors in transgenic mice with human c-Ha-ras gene contained somatically activated transgenes. AB - Two independent transgenic mouse lines carrying human hybrid c-Ha-ras genes with their own promoter region encoding prototype products, were established. In these lines, about 50% of transgenic offspring had tumors within 18 months. The tumors developed in restricted tissues and about 60% of affected mice had angiosarcomas. The transgenes were expressed both in the tumors and in all normal tissues. However, somatic mutational activation was detected only in the transgenes of the tumors. The point mutation at the 61st codon, from CAG(Gln) to CTG(Leu), was detected in all angiosarcomas (22/22), some lung adenocarcinomas (3/11) and Harderian gland adenocarcinomas (4/7) in both lines. The other point mutation at the 12th codon from GGC(Gly) to GTC(Val) was detected in two of the four skin papillomas. No mutations on these codons were detected in normal tissues of transgenic mice. Nontransgenic littermates had no tumors at all. From these results, it was strongly suggested that the mouse tumors do not develop only by the expression of the transgenes, and that definite somatic point mutation of the human c-Ha-ras transgenes in certain cell types may be a causative event in tumorigenesis in these transgenic mice. PMID- 2202953 TI - [Dental concerns at various ages]. PMID- 2202952 TI - Early and late responses to induction of rasT24 expression in Rat-1 cells. AB - We have used a series of Rat-1 cell lines carrying a Zn-inducible human c-Ha-ras oncogene construction (MTrasT24) to evaluate the effect of varied ras oncogene expression on the expression of genes and proteins related to morphologic transformation in vitro. In response to the expression of the ras oncogene, at least two different classes of events occur. These events, referred to as 'early and late' events, are dependent on distinctively different accumulated levels of the ras oncoprotein. Relatively low levels of activated c-Ha-ras p21 protein (1.5 2.5 times the proto-oncogene level) stimulate rapid entry of quiescent (G0) cells into the cell cycle and result in increased steady state c-myc and glucose transporter mRNA levels which are detectable as early as 3-6 h after zinc addition. In contrast, morphologic transformation develops more slowly and does not appear until 72-96 h after Zn++ stimulation in cells with very low basal levels of activated p21 (MR4 cells) and 24-48 h in cells with higher basal levels (MR5 cells). These morphologic changes depend on the accumulation of significant amounts of the ras oncoprotein (greater than 4 to 5 times the proto-oncogene level) and are accompanied by large increases in the steady state mRNA levels of transin and TGF-alpha and decreases in PDGF-receptor mRNA and fibronectin protein and mRNA levels. In addition, the level of a novel cytoplasmic protein species (referred to as p29), which is stained by a monoclonal antibody for ras, is dramatically reduced in response to these levels of activated ras protein. Thus changes in morphology and gene expression induced by rasT24 occur sequentially and are quantitatively dependent on activated ras expression. PMID- 2202955 TI - National Association of Orthopaedic Nurses. Chapter presidents' listing 1989 1990. PMID- 2202954 TI - Patient controlled analgesia and GI dysfunction. AB - A prospective randomized study of 300 total joint replacement patients was done comparing the gastrointestinal (GI) side effects of morphine, meperidine, and nalbuphine given by patient controlled analgesia (PCA). All three groups of patients developed some form of GI dysfunction, but no significant difference was found among the three narcotics used. It was found that normal GI assessment in the initial postoperative period does not guarantee that GI function will remain normal. This finding indicates a need for extended nursing assessment of the GI status of the postoperative PCA patient. PMID- 2202957 TI - A symposium on the surgical pathology of the prostate. PMID- 2202956 TI - Low-grade sarcomas. PMID- 2202958 TI - Pathology of meningiomas. PMID- 2202959 TI - Cystic tumors of the pancreas. PMID- 2202960 TI - New applications of monoclonal antibodies to the diagnosis and prognosis of breast cancer. PMID- 2202961 TI - The myofibroblast in breast disease. PMID- 2202962 TI - Immunohistochemistry in the differential diagnosis of breast diseases. AB - Immunohistochemical techniques provide previously unavailable information about the composition of breast lesions. These data must be evaluated in the pathologic context and must not be used to support a diagnosis inconsistent with the morphological appearance. In the diagnosis of breast lesions, we have found immunohistochemistry of most use in classifying poorly differentiated and spindle cell tumors. PMID- 2202963 TI - The cytogenetics and molecular genetics of lung cancer. Implications for pathologists. AB - The interactions of cytogenetic and molecular genetic changes in the pathogenesis and progression of lung cancer are complex. To the practicing pathologist, certain of these changes may prove useful as diagnostic or prognostic markers and may help in selecting patients for particular types of therapy. Changes such as 3p14-23 deletions, c-myc amplification, and L-myc RFLPs have already been reported to predict aggressive behavior in lung cancer. Future studies will clarify the application of these changes to the clinical care and treatment of patients with carcinoma of the lung. PMID- 2202964 TI - Autopsy technique for neck examination. I. Anterior and lateral compartments and tongue. PMID- 2202965 TI - Immunohistochemical phenotyping of malignant melanoma. A procedure whose time has come in pathology practice. AB - Experience has shown that markers created in research laboratories can be adapted to everyday surgical pathology practice for malignant melanomas. These studies are feasible and readily conducted on frozen tissue as is routinely done in typing of lymphoma. The demonstration of heterogeneity using this monoclonal antibody panel, and other antibodies yet to come, may be important for prognostication. Tumor cell heterogeneity of surface antigens reflects disruption of the tumor cell's patterned gene expression. This should be regarded as an indication of different clones of cells (subsets) with a tumor, whether primary or secondary. It is entirely possible that autologous immune cells can kill or at least restrict the growth of subsets of melanoma cells having certain surface antigenic phenotypes while they are incompetent to handle other subsets. This would enable a particular phenotype within a primary melanoma to survive and escape the immunologic regression known to occur in 3 to 6 percent of these tumors. Such patients may present years later with metastases in the brain, liver, gastrointestinal (GI) tract, or lymph nodes. There are also implications in chemotherapy and chemoimmunotherapy for melanoma in this regard. It could be theorized that these agents may dispose of or restrict the growth of some phenotypes, leaving others in a resistant state. Perhaps the MDR gene is activated. Alternatively a tumor suppressor gene(s) could be absent or inactivated, as in neuroblastoma and carcinoma of the breast and lung. Markers present at the cell membrane surfaces and in the membranes themselves constitute an important field for study in the understanding of tumorigenesis. Many of these markers are present in embryos as early as the 4-to-8-cell stage and in blastocysts. Embryonic antigens in the intercell mass of blastocysts are stage specific embryonic antigens. They are signals for organ development and the differentiation of cells. At various stages of this development, these markers disappear, especially upon differentiation into tissue types and specific organs. These cell signals are therefore organogenesis markers. Detecting a given antigen is not simple because it may be present but not immunohistochemically detectable because glycosylation, acetylation, phosphorylation, or sulfation have not taken place, or have resulted in a structural conformation not recognized by monoclonal antibodies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2202966 TI - Tumors and cysts of the paratesticular region. PMID- 2202967 TI - Hypothesis of classification of pulmonary fibroses. AB - A new framework for pulmonary fibroses may be obtained by distinguishing the "true" forms (solely collagen hyperplasia) from the "false" forms or mesenchymal fibril lung diseases (collagen, reticular and elastic hyperplasia with neo angiogenesis): the "true fibroses" are then divisible into those not causing architectural subversion of the lung and those which bring it about. Pulmonary architectural subversion is common to true granulomatous fibroses and mesenchymal fibril lung diseases: it is, in our opinion, the product of a combination of factors, including the hyperactivity of a fibroblast sub-population normally in the minority, stimulated by T lymphocytes which are activated by an autoimmune response to type I collagen produced in excess. PMID- 2202968 TI - Blueprint for a perinatal bereavement support group. AB - Key aspects of developing a mutual self-help perinatal bereavement support group include planning for the logistics of the meeting, choosing a facilitator(s), informing the public and conducting the meeting. Once the group has begun, the role of the facilitator is paramount in attending to the group's developmental issues, fostering an environment that supports members' needs and referral when necessary. PMID- 2202969 TI - The multiple faces of immune deficiency in children. AB - Immune deficiency in children comes in many different forms. This article differentiates these forms from a physiologic perspective and identifies implications for the pediatric nurse. PMID- 2202970 TI - State involvement in maternal and child health care. PMID- 2202971 TI - Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). AB - Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) is a unique disease of unknown etiology with a childhood predilection. Reports have established the worldwide distribution of the disorder. Although peripheral lymphadenopathy is the most common mode of presentation, numerous studies and individual case reports have established the fact that 30-40% of affected individuals have extranodal manifestations particularly in the head and neck region where the adenopathy tends to be concentrated. As yet, the pathogenesis of SHML has not been established but speculation relates the disorder to an aberrant response to an unspecified antigen, possibly an infectious organism. Because of the clinical manifestations, the radiographic features of SHML are not pathognomonic but rather engender a differential diagnosis which includes lymphomatous, pseudolymphomatous and infectious conditions. Appropriate imaging of patients with SHML depends upon presenting symptoms and signs. Radionuclide bone scanning may be helpful in the evaluation of suspected skeletal lesions or joint symptoms. Gallium scanning is often positive in nodal disease and CT, MRI and sonography are helpful in the evaluation of extranodal sites of involvement such as the orbit, eyelid, upper aero-digestive tract and retroperitoneum. PMID- 2202972 TI - Intraspinal extension of paraspinal masses in infants: detection by sonography. AB - Spinal sonography has been helpful in the study of congenital anomalies involving the spine in fetuses and infants. We have found this technique also to be useful in the detection of intraspinal extension of paraspinal masses. PMID- 2202973 TI - Accuracy of ultrasonic bladder volume measurement in children. AB - The accuracy of ultrasonography in assessing the bladder volume in 13 children with normal bladder contours was determined using the formula D x H x W (depth x height x width) with a mean error of 15.7%. This formula tends to overestimate the bladder volume in these patients. Multiplication by a correction factor of 0.9 yields a mean error of 11.5%. The accuracy of this evaluation is not dependent upon the bladder volume as the mean error was the same in those children whose bladder volume was either less than or greater than 150 cc. In addition, the accuracy of ultrasonography in assessing bladder volume was evaluated in 7 patients with an abnormal bladder contour (trabeculation, diverticula, etc.); mean error was 14.7%. In these 7 patients there was no predictable under or overestimation of bladder volume. In the children with abnormal bladder contours on ultrasound, the correction factor of 0.9 should not be used, as it does not add to the accuracy of the procedure in any individual patient. This technique is still valuable, however, in children with an abnormal bladder for it allows estimation of the extent of emptying without invasive catheterization. PMID- 2202974 TI - Air embolism with survival in a neonate. AB - Air embolism in neonates is usually fatal. We describe an infant who survived and discuss the pathogenesis and management of this condition. PMID- 2202975 TI - Swollen neck in children: a report of two cases. AB - Two cases of swollen neck during straining, coughing, or crying caused by internal jugular vein dilatation that were diagnosed by ultrasonography and computed tomography are presented. With a review of the literature the aetiology and diagnostic procedure are discussed. PMID- 2202976 TI - Sonographic detection of congenital pancreatic cysts in the newborn: report of a case and review of the literature. AB - A case of congenital pancreatic cysts detected antenatally by ultrasound is presented. This is the second case detected antenatally. Congenital pancreatic cysts should be included in the differential diagnosis of upper abdominal cystic masses in the fetus and newborn infant. PMID- 2202977 TI - Glomerulocystic kidney disease: case report. AB - A newborn infant with abdominal masses was found to have Glomerulocystic Kidney Disease. Imaging showed markedly enlarged kidneys with multiple macroscopic cysts. Radiographic and clinical findings are discussed. PMID- 2202978 TI - An unusual case of craniofacial fibrous dysplasia presenting in early infancy. AB - Fibrous dysplasia (FD) of bone is one of the most frequently encountered anomalies of skeletal development. It may involve one or more bones and, particularly when polyostotic, is sometimes associated with abnormal skin pigmentation and endocrine abnormalities. FD occurs mainly in large limb bones, ribs, and craniofacial bones in older children and young adults. Usually craniofacial involvement is detected because of local swelling or asymmetry of the face or head. Neurological symptoms, primarily due to involvement of the foramina, have been reported but are not common. Infantile fibrous dysplasia of the craniofacial region has rarely been reported. PMID- 2202980 TI - The politics of Medicaid: 1980-1989. AB - Grim statistics on infant mortality and women's health alone are not enough to keep Medicaid funded. What is also needed is a strong, vociferous lobby dedicated to protecting these important programs. PMID- 2202979 TI - Our mothers' stories. AB - The recollections of Depression-era nursing students interviewed in the Philadelphia Oral History Project bring to vivid life the documented history of the period and illustrate how far nursing and nursing education has come in the intervening 50 years. These stories also reveal that some of today's most disturbing social problems, considered unique to our time, have deep roots in the past. PMID- 2202981 TI - [Serotonin and the lungs]. PMID- 2202982 TI - The measurement of anxiety. AB - Selected contemporary highlights and issues in the field of anxiety measurement are discussed. The concepts of state and trait anxiety, and the most widely used measures of these, are reviewed. A measure of state anxiety is essential in some clinical and experimental research and it is often very useful in clinical practice. Whilst existing measures are satisfactory for some purposes, none adequately assesses the psychological, somatic and behavioural components of anxiety. The measurement of trait anxiety is also important in some clinical research and as part of the assessment of selected patients. In some circumstances, self report measures of trait anxiety should be used in conjunction with a measure of social desirability. Patients who score low both on trait anxiety and social desirability may respond differently to experimental stressors from those who score low on trait anxiety and high on social desirability. This may have a number of implications, for example in the area of psychoimmunology. Four scales are reviewed in more detail: the Courtauld Emotional Control Scale, the Hospital Anxiety and Depression Scale, the Clinical Anxiety Scale and the Fear Questionnaire. Finally, some future directions for research are outlined. PMID- 2202983 TI - The management of anxiety in general practice. AB - This paper attempts to summarize a personal approach to the management of anxiety and to some of the problems that have been recently encountered in respect of public attitudes to benzodiazepines. In the management of anxiety 'psychological' approaches should be sought where possible. There are, however, occasions, both in connection with normal and abnormal anxiety, when drug therapy is appropriate or where perhaps a combination of 'psychological' and pharmacological methods represents the most expedient course of action. Prescribers need an 'armamentarium' of drugs, since no one type of anxiolytic meets all our needs. The paper suggests limited use of benzodiazepine, beta blockers, low dose neuroleptics, some newer anxiolytic agents and certain specific drugs. The general practitioner needs to tailor his choice to the needs and attributes of particular patients. PMID- 2202984 TI - [Biosynthesis of alkaloids by mycelial fungi (review of the literature)]. AB - Evidence for the occurrence of alkaloids in mycelial fungi, pathways of their biosynthesis and types of regulation are presented. The effect of some factors on the alkaloid production is discussed. In literature, the biosynthesis and the metabolism of diketopiperazine and ergot alkaloids in Penicillium fungi are covered most completely. PMID- 2202985 TI - [Reduction of nitro-substituted 1,2-dihydro-3H-1,4-benzodiazepine- 2-ones by E. coli cells immobilized in carrageenan]. AB - Reduction of nitro-substituted 1,2-dihydro-3H-1,3-benzodiazepine-2-ones by E. coli cells immobilized in carrageenan was studied. The corresponding amines are the sole products with a 100% yield as compared to the native cells. Conditions for immobilization of E. coli cells in the home-produced carrageenan was worked out: the cell to carrageenan ratio is 1:10 (w/w), granulation in toluene at 0 (+)4 degrees, treatment with 0.3-0.4 M KCl. The carrageenan-immobilized cells are stable upon storage, repeated usage (after 10 cycles about 80% of the initial activity is retained), and when being used in column fermenters. PMID- 2202986 TI - [Sterol level in Saccharomyces cerevisiae mutants with altered ergosterol biosynthesis]. AB - The sterol content in Saccharomyces cerevisiae mutants defective in the synthesis of cyclic ergosterol precursors has been studied. It was found that strains with mutational blocks involving the stages of zymosterol side chain methylation at C24 and delta 8----delta 7 isomerization accumulated twice more sterols as compared to parent strains. Regulation of the ergosterol biosynthesis is discussed. PMID- 2202987 TI - [Isolation of Staphylococcus aureus protoplasts using lysoamidase]. AB - The effect of the bacteriolytic enzyme preparation, lysoamidase, on Staphylococcus aureus 209P cells was studied. The protoplast formation was examined by spectrophotometric, biochemical and electron microscopic methods. Optimal conditions for isolation of S. aureus protoplasts were chosen. The susceptibility of S. aureus cells to lysoamidase depended on the culture age: the maximum effect was observed in the logarithmic growth phase. The protoplast yield was 80% when 1 M sucrose was used as an osmotic stabilizer. Lysoamidase caused local disruptures of the staphylococcus cell walls, which resulted in the formation of osmotically fragile spheroplasts and the release of protoplasts into the medium. The protoplasts obtained could retain 85-90% of the respiration activity and were able of cell wall regeneration. PMID- 2202988 TI - Smoking cessation and pregnancy intervention trial: preliminary mid-trial results. PMID- 2202989 TI - Nonadherence to chemoprevention regimens: a ton of prevention.... PMID- 2202990 TI - Development of a contingency recruitment plan for a phase III chemoprevention trial of cervical dysplasia. AB - Development of contingency recruitment plans in cancer chemoprevention research is as important as formulation of the initial plan. We found that requesting recruitment information from our initial CTCD subjects provided a framework for our contingency plan. The revised recruitment plan consisted of: 1) calling and sending letters to community gynecologists in private practice or affiliated with HMO's to explain the study and ask for referrals; 2) continued personal contact by the principal investigator with referring physicians; 3) sending thank you and follow-up letters to every physician who referred patients to the study; 4) soliciting Papanicolaou smear reports from HMO's if physicians of women with abnormal Papanicolaou smears gave permission to pathologists to release this information; 5) utilizing free media such as feature articles on the CTCD in local papers, public service announcements, and television "spots;" 6) continued use of brochures and posters printed for the initial recruitment effort; and 7) continued presentations to local professional physician and nurse groups about the study. Our contingency plan to date has provided us with 100% of our projected accrual. Thus, our recruitment methods have proved to be effective in accruing subjects for this cancer chemoprevention trial. PMID- 2202991 TI - Current status: evaluation of dietary fat reduction as secondary breast cancer prevention. The Nutrition Adjuvant Study. PMID- 2202992 TI - An overview of female breast cancer. PMID- 2202994 TI - Approaches to colorectal cancer screening and evaluation. PMID- 2202993 TI - An evaluation of BSE frequency and quality and their relationship to breast lump detection. PMID- 2202995 TI - Organizing cancer control research in the community setting. PMID- 2202996 TI - Will community physicians participate in rigorous studies of cancer control? The methodology and recruitment of a randomized trial of physician practices. PMID- 2202997 TI - The advantages of using the clinical trials model for cancer control research. PMID- 2202999 TI - Increasing adherence to a provider-implemented smoking cessation intervention for head and neck cancer patients. PMID- 2203000 TI - An SAR study of the mutagenicity of PAH compounds in Salmonella typhimurium. PMID- 2202998 TI - A comparison in attitudes toward cancer control research between family practice residents (FPR) and primary care practitioners (PCP). PMID- 2203001 TI - Structure activity analysis of azo dyes and related compounds. PMID- 2203003 TI - In vitro mammalian cell genotoxicity assays: their use and interpretation. PMID- 2203002 TI - Role of metabolism in benzene-induced myelotoxicity and leukemogenesis. PMID- 2203004 TI - Overview of in vivo mammalian testing systems. PMID- 2203005 TI - Micronuclei in vivo. PMID- 2203006 TI - The cytokinesis-block micronucleus assay in nucleated cells. PMID- 2203007 TI - Identification of rodent carcinogens by an expert system. AB - CASE, an artificial intelligence method for identifying structural determinants responsible for biological activity was applied to the U.S. National Toxicology Program (NTP) cancer bioassay results. CASE identified structures which were significantly associated with rodent carcinogenicity. On the basis of these structural determinants CASE exhibited a sensitivity of 0.98 and a specificity of 1.00. CASE showed a similarly remarkable performance in predicting the carcinogenicity, or lack thereof, of chemicals not in the NTP data base. A comparison between the activating structures (biophores) responsible for mutagenicity in Salmonella and rodent carcinogenicity showed a significant overlap, verifying that there are structural commonalities between the two phenomena. CASE also identified biophores significantly associated with the activity of non-genotoxic carcinogens, thereby suggesting the unexpected possibility that there is a structural commonality among the chemicals included in this group. A comparison between the biophores responsible for carcinogenicity in mice and rats resulted in the identification of common ("universal") biophores. It is suggested that agents which contain "universal" biophores are more likely to present a risk to human than carcinogens that do not possess such biophores. CASE also permitted the recognition of species-specific carcinogenic biophores. While the former are primarily electrophiles or potential electrophiles, the latter represent non-electrophilic structures. PMID- 2203008 TI - The detection of aneugens using yeasts and cultured mammalian cells. PMID- 2203009 TI - On the validation of the system of Aspergillus for testing environmental aneugens. PMID- 2203011 TI - Cytogenetics: overview. PMID- 2203010 TI - Aneuploidy studies in mammals. PMID- 2203012 TI - Chromosomal abnormalities in hematologic malignant diseases. PMID- 2203013 TI - Direct measurement of chromosome repair by premature chromosome condensation. PMID- 2203014 TI - Germinal imprinting in chromosome mutation. PMID- 2203015 TI - DNA homology and chromosome stability: a sensitive yeast genetic system for identifying double-stranded DNA damage. AB - Recombination is required for the repair of many types of lesions and it can be a source of genetic diversity. We are investigating the requirements for homology in recombination and the consequences of recombination between DNA divergent sequences. Recombination between sequences of partial homology could account for chromosome rearrangements leading to the generation of novel genes and possibly involved in initiating events in carcinogenesis. We have developed a method for examining the role of homology between a specific pair of chromosomes in "protecting" chromosomes against DNA damage (Resnick et al., 1989). In the yeast Saccharomyces cerevisiae DNA double-strand breaks (DSBs) induced in diploid G-1 cells are normally repaired by recombination between homologous chromosomes. When homology is greatly reduced the DSBs lead to chromosome loss. These observations suggest that the system that has been used to study the role of recombination in repair can also be used to measure double-strand damage at low biologically meaningful doses. PMID- 2203016 TI - Fragile site analysis: its significance in environmental mutagenesis. PMID- 2203017 TI - Mechanisms of chromosome aberrations. PMID- 2203018 TI - Inducible repair of cytogenetic damage to human lymphocytes: adaptation to low level exposures to DNA-damaging agents. PMID- 2203019 TI - Cytogenetics of human sperm: structural aberrations and DNA replication. PMID- 2203020 TI - Human sperm chromosome complements: effects of donor age, freezing and segregation in translocation and inversion carriers. PMID- 2203021 TI - Exposure to, and activation of, the food derived mutagenic heterocyclic amine MeIQx. PMID- 2203022 TI - Mutagenicity of drinking waters in Finland. PMID- 2203023 TI - Identification of food mutagens. PMID- 2203025 TI - Genetic toxicology of food products. PMID- 2203024 TI - Mutagens in chlorinated water. PMID- 2203026 TI - Dietary genotoxins and the human colonic microflora. PMID- 2203027 TI - Metabolism of heterocyclic amines in cooked food. PMID- 2203028 TI - Monitoring of food mutagens. PMID- 2203029 TI - Monoclonal antibody based immunoassays for cooking-induced meat mutagens. PMID- 2203030 TI - Epidemiologic studies of fecal mutagenicity, cooked meat ingestion, and risk of colorectal cancer. PMID- 2203031 TI - Common and uncommon indoor sources of mutagenic aerosol particulate matter. PMID- 2203032 TI - Mutagenicity of 30 Chinese herbs and pharmaceuticals. PMID- 2203033 TI - Comparative mutagenicity and genotoxicity of the antiparasitic drugs, mebendazole, flubendazole and flubendazole oxime. PMID- 2203034 TI - Schistosomiasis drugs: an ICPEMC study. PMID- 2203035 TI - Mutagenicity of burnt gun propellants. PMID- 2203036 TI - Genotoxicity of new Japanese chemicals. PMID- 2203037 TI - Environmental mutagenesis in Thailand. PMID- 2203038 TI - Mechanisms of inhibitors of genotoxicity: relevance in preventive medicine. PMID- 2203039 TI - Study on behavior of mutagens from municipal incinerators by means of Ames assay. PMID- 2203040 TI - The role of X-ray-induced DNA repair processes in mutagenesis and carcinogenesis. PMID- 2203041 TI - Antimutagenic effects of Chinese medicines. PMID- 2203042 TI - Diet as a source of inhibitors of mutagenesis. PMID- 2203043 TI - Activation of promutagens by plant cell systems. AB - The plant cell/microbe coincubation assay is a sensitive and flexible assay for use in screening for plant-mediated promutagens as well as in basic mutation research. By using plant cell cultures of crop plants, xenobiotics used in agriculture can be evaluated for their mutagenic properties. PMID- 2203044 TI - Tradescantia-micronucleus test on clastogens and in situ monitoring. PMID- 2203045 TI - Genotoxicity of pesticides and plant systems. PMID- 2203046 TI - Transgenics as a new source of isozyme systems. PMID- 2203047 TI - Isozymes and the micro organization of organellar structure and function. AB - One of the most valuable of the wide-ranging attributes of isozymes is the novel insight they allow into some of the most complex aspects of cell biology. The microorganization of subcellular structure and function is one such area, and the present study utilizes the peroxisome as an example of these applications. The biological characteristics of the major enzymic component of this organelle, catalase, have been detailed in mammalian tissues, where the enzyme exhibits a complex heterogeneity, which is due to multiple types of epigenetic modification. The major native multiplicity, however, has been demonstrated as attributable to sialic acid attachment to the enzyme. In studying the compartmentalization of these isozymes within liver cells, the technique of differential extraction with digitonin was employed, and evidence provided which supports the presence of an appreciable proportion of catalase activity in the cytoplasmic compartment. The source of these cytoplasmic isozymes was traced to release from the peroxisome, and the mechanism of this release identified with variations in the content of lysophosphatidyl choline in the peroxisomal membrane. Studies of the association of catalase with the subcellular membranes indicated an appreciable ionic interaction which varied with membrane type and isozyme status. Activity was enhanced in the bound form, providing support for the interpretation of a general protective role of this enzyme against oxidation of membrane components within the cell. Overall, these studies are considered to contribute significantly to current knowledge of the biological role and subcellular localization of catalase in relation to organellar structure and function. PMID- 2203048 TI - Molecular structures and evolution of mouse isozyme genes functioning in the malate-aspartate shuttle. AB - To examine molecular mechanisms of transcription of mammalian isozyme genes functioning in the malate-aspartate shuttle and to observe structural and evolutionary relationships, we investigated gene organizations of cAspAT and mAspAT, and cMDH and mMDH, and isolated and characterized cDNAs and genomic DNAs for these isozymes in mice. The deduced amino acid sequences of mouse cAspAT and mAspAT showed about 47%, and those of mouse cMDH and mMDH, about 23% overall homology. Surprisingly, the homology between the mouse cMDH and thermophilic bacterial MDH, as well as the homology between the mouse mMDH and E. coli MDH, markedly exceeds the intraspecies sequence homology between mMDH and cMDH from mice. The first duplication of a common ancestral MDH gene should thus have occurred long before the emergence of the eukaryotic cells, and subsequently, the mammalian mMDH and E. coli MDH genes have evolved from one of the duplicates. The mammalian cMDH and Thermus flavus MDH genes have no doubt evolved from one of the other duplicates. Moreover, structural organizations of the two-pairs of isozyme genes indicated that introns antedate the divergence of these mitochondrial and cytosolic isozyme genes. The 5' ends of all four isozyme genes lacked the TATA and CAAT boxes characteristic of eukaryotic promoters but did contain G + C-rich sequences and multiple transcription-initiation sites. We found several highly conserved regions in the 5' flanking sequences between mAspAT and cAspAT, between mMDH and mAspAT, and between cMDH and cAspAT genes. PMID- 2203049 TI - Pollen and kernel development in maize: analysis of gene expression. PMID- 2203051 TI - Gene expression for calpain isozymes in human hematopoietic system cells. AB - Calpain (EC 3.4.22.17; Ca2(+)-dependent cysteine endopeptidase) is known to exist in two forms of isozyme. Calpain I requires low (or microM)-Ca2+ for activation and calpain II requires high (or mM)-Ca2+. Both isozymes consist of one heavy (approx.80 kDa) and one light (approx. 30 kDa) subunit each. The heavy subunits of isozymes I and II are different genetic products, while the light subunits are identical. Antibodies respectively specific for the heavy subunits of pig calpains I and II were raised in rabbits, and the affinity-purified IgG proteins were used for Western blot analysis. When 23 human hematopoietic system cells were examined for the degree of their expression of the genes for calpains I and II, all of them were found to contain calpain I of detectable amounts in their cytosolic fluid. By contrast, only nine cell-line cells were positive in calpain II, and they were, without exception, the lineage which had been infected with HTLV-I, the retrovirus responsible for human adult T-cell leukemia. The enhanced production of calpain II in HTLV-I infected T-cells was also confirmed by running chromatographic analyses on the homogenates of these cells, and comparing them with those of uninfected T-cells. When YT-C3 cell, which is an uninfected, natural killer-like cell, was transfected with HTLV-I gene, the resulting transformed stable cells, YT-4 and YT-5.1, were found to produce increased amounts of calpain II concomitant with that of interleukin (IL)-2 receptor protein. These results suggest that the gene expression for calpain isozymes may vary during the course of differentiation of T-lymphocytes. The mechanism of regulation of calpain isozyme genes and the biological significance of the variation in expression during differentiation still remain unanswered. PMID- 2203052 TI - Developmental expression of lactate dehydrogenase isozymes during spermatogenesis. PMID- 2203050 TI - Oncodevelopmental alkaline phosphatases: in search for a function. PMID- 2203053 TI - Targeting, import, and processing of nuclear gene-encoded proteins into mitochondria and peroxisomes. AB - I have herein discussed two gene-enzyme families in maize whose protein products participate to purge toxic oxidants from cells, and are thus of importance to all aerobic organisms. We have demonstrated that plant mitochondria import precursor proteins (i.e., preSOD-3) in a manner analogous to other eukaryotic cells. The "transit peptide" (TP) of preSOD-3 is 31 amino acids long and has similar properties to other reported TPs for mitochondrial and chloroplastic proteins. Import to peroxisomes is uniquely different from that for mitochondria and chloroplasts in that no consensus presequence seems to be involved. Instead, targeting signals seem to be integral parts of peroxisomal proteins. These studies are important from a genetic engineering perspective in that it is not only important to express genes in specific tissues, but also within specific subcellular compartments. Expression of donor genes in appropriate cellular compartments of host cells will be critical for maintaining a stable, functional protein in the plant. Manipulation of metabolic pathways in plants requires that engineered proteins be efficiently and effectively expressed in the correct subcellular compartment and during the appropriate developmental time frame. The use of engineered proteins with altered topogenicity may not only prove useful in studying the role(s) of such proteins in metabolism, they may also serve to enhance our understanding of inter-organellar communication within the cell. PMID- 2203054 TI - Expression of rat aldolase A gene and analysis of AH promoter region of the gene. PMID- 2203055 TI - Indoleacetaldehyde dehydrogenase (IAA1DH) activity in the apical meristems and protein profiles during seed germination. PMID- 2203056 TI - Pollen selection: efficiency and monitoring. PMID- 2203057 TI - The mink X chromosome: organization and inactivation. PMID- 2203058 TI - Biochemical analyses of inbreds and their heterotic hybrids in maize. AB - Since Shull's original description of heterosis, breeders have made wide use of this phenomenon. However while breeders and agronomists have been utilizing heterosis as a means of improving crop productivity, the biological basis of heterosis remains unknown. It is generally believed that our understanding of heterosis will greatly enhance our ability to form new genotypes either to be used directly as F1 hybrids or to form the basis for the selection programs to follow. Efforts have been made to understand the phenomenon. They have been directly related to our capabilities for genetic analyses through the years. So, while the original data came out of studies at the phenotypic morphological level they were followed by physiological and later by biochemical data. With the advent of electrophoresis and the consequent ease of accumulation of data related to isozyme variability, a number of attempts have been made to relate genetic relatedness of inbreds with the performance of their F1 hybrid. An inherent difficulty of this approach arises because of the pedigree diversities among the parental lines. To overcome this problem the same approach is followed in lines of similar pedigree, e.g., coming out of the same original population (F2 of a single F1 hybrid) after selection. The data indicate a significant positive correlation between heterozygosity of parental inbreds and heterosis of their respective F1 hybrid estimated as deviation from the mid-parental value. Some recent data from studies at the total protein level will also be discussed. PMID- 2203060 TI - Human and mouse lactate dehydrogenase genes A (muscle), B (heart), and C (testis): protein structure, genomic organization, regulation of expression, and molecular evolution. PMID- 2203059 TI - Molecular evolution from argininosuccinate lyase to delta-crystallin. AB - cDNA clones for rat argininosuccinate lyase, a urea cycle enzyme, were cloned and amino acid sequence of the enzyme was predicted. The rat enzyme is 54% identical with the yeast enzyme, which is involved in arginine biosynthesis, thereby indicating that this urea cycle enzyme evolved from the arginine biosynthetic enzyme. A striking similarity (64% identity) was found between amino acid sequences of rat argininosuccinate lyase and chicken delta-crystallin, a major structural protein of the eye lens. The gene for the rat argininosuccinate lyase was cloned and its structure was determined. This gene is a single-copy gene about 14 kilobases long and is split into 16 exons. A comparison with chicken delta-crystallin genes revealed that all introns interrupt the protein-coding regions at homologous positions. This close similarity in structural organization provides strong evidence for the view that the chicken delta 1- and delta 2 crystallin genes evolved by recruitment and duplication of the preexisting argininosuccinate lyase gene and that delta 2-crystallin is probably the direct homologue of argininosuccinate lyase. PMID- 2203061 TI - Isozymes of marsupials: implications for understanding mammalian evolution. PMID- 2203063 TI - Pyruvate kinase deficiency. AB - PK deficiency is the most common and well characterized erythroenzymopathy in the Embden-Meyerhof glycolytic pathway associated with hereditary hemolytic anemia. History of discovery, clinical features, biochemical studies, as well as recent studies on molecular level were reviewed, with a stress on our own studies. As reference materials, Tables 2 and 3 are attached. PMID- 2203064 TI - Aspartate aminotransferase isozymes and their clinical significance. PMID- 2203062 TI - Isoprotein changes in aging: biochemical basis and physiological consequences. PMID- 2203065 TI - The subcellular compartmentation of creatine kinase isozymes as a precondition for a proposed phosphoryl-creatine circuit. AB - The idea of a PCr-circuit is supported by the fact that in fully differentiated and highly specialized cells with high sudden energy turnover, e.g., skeletal and cardiac muscle [Wallimann and Eppenberger, 1985], brain and retina photoreceptor cells [Wallimann et al, 1986a], spermatozoa [Tombes and Shapiro, 1985; Wallimann et al, 1986b] and Torpedo electrocytes [Wallimann et al, 1985] mitochondrial CK is generally found in conjunction with cytosolic CK's with a significant fraction of the latter being associated subcellularly in a compartmented fashion at intracellular sites of high energy turnover. It is also becoming apparent that some of the cytosolic CK is specifically associated with membranes possibly via membrane anchors, e.g., with the SR-membrane where CK was shown to be functional by supporting a significant portion of the maximal Ca2(+)-pumping rate [Rossi et al, 1988; submitted]. Similar membrane associations of CK have been shown with the post-synaptic acetylcholine-receptor-rich membrane, the invaginated, and non innervated face membrane of electrocytes, rich in Na+/K+ ATPase as well as with synaptic vesicles [Wallimann et al, 1985], with the sperm-tail plasma membrane [Wallimann et al, 1986a], and recently also with rod outer segment plasma membranes of bovine photoreceptor cells [Quest et al, 1987; Hemmer et al, 1989]. Thus, for all the above cells the PCr-circuit seems to represent an efficient, flexible, and highly responsive accessory, crucial not only as an energy back-up system, but also as a regulator of energy flux (channeling) and as a fine-tuning device of local ATP-levels. The strength of such a regulated channeling circuit operating at relatively low adenine nucleotide levels compared to the high total PCr and Cr pools, which are metabolically inert, is its high sensitivity towards ADP [Wallimann et al, 1984] that is preventing in excitable cells the accumulation of ADP and AMP unless severe stress, such as hypoxia or ischaemia is imposed. Additional details concerning the PCr-circuit model in muscle and our current ideas about the structure-function relationships of mitochondrial have been described elsewhere [Wallimann and Eppenberger, 1985; Schlegel et al, 1988; Schnyder et al, 1988].(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2203066 TI - Relationship between lipase and esterase. AB - There are at least two sites on the lipase which are concerned with catalysis: the catalytic site and the hydrophobic recognition site (lipid-binding site). The recognition site may be destroyed by mild proteolytic digestion, but the catalytic site may not be changed by this treatment. Mild treatment with trypsin caused change in the catalytic properties of hepatic triglyceride lipase; the water-insoluble ester-hydrolyzing activity of hepatic triglyceride lipase decreased, whereas the water-soluble ester-hydrolyzing activity did not change. After proteolytic digestion, hepatic triglyceride lipase resembles esterase since it hydrolyzes the water-soluble substrate better than the water-insoluble substrate. Conversely, esterase was converted to lipase by treatment with phospholipid. Cardiolipin in a concentration-dependent fashion enhanced triolein hydrolysis of human serum carboxylesterase and this effect was associated with a dose-dependent decrease in water-soluble tributyrin hydrolysis. Based on these results, we propose the hypothesis that lipase and esterase have similar catalytic sites and that addition of a hydrophobic recognition site to esterase causes conversion of esterase to lipase (Fig. 9). PMID- 2203067 TI - Structural studies on aldolase isozymes through protein engineering. AB - Enzymatic studies on aldolase isozymes have been carried out by techniques of protein engineering. Site-directed mutagenesis helps us to verify the roles of amino acid residues in catalytic reactions. Chimeric fusion proteins give us information about the regions which specify the characteristics of the isozymes. The results are: (1) In aldolase A, COOH terminal Tyr and Lys-107 residues play important roles in catalysis, especially in binding of FDP. (2) Aspartic acid at the 128th residue in aldolase A is essential to thermostability; no other residue such as glutamic acid can substitute for it. (3) Studies on chimeric fusion proteins indicate that the C-terminal region (including C-terminus Tyr) or aldolase A is responsible for its substrate specificity, which is not seen in aldolase B. (4) A region near NH2 terminus in aldolase B determines its specific structure. (5) The region including His-107, Asp-128, and Tyr-137 (B-A junction of BA137) is located in a turn which is exposed outward (a model architecture by Sygusch et al [1987]). In BA137, this region would be constrained, and play a significant role in catalysis, thermostability, etc. (6) Tertiary structure of aldolase B seems to be dissimilar to that of aldolase A. PMID- 2203068 TI - Animal models of anxiety based on classical conditioning: the conditioned emotional response (CER) and the fear-potentiated startle effect. AB - Stimuli consistently paired with shock become capable of suppressing ongoing operant or consummatory behavior (the conditioned emotional response--CER) or elevating the amplitude of the startle reflex (fear-potentiated startle). These changes are used to infer a central state of fear which involves the central nucleus of the amygdala and its efferent projections to the brainstem. The present paper reviews how psychoactive drugs affect these measures. Both the CER and fear-potentiated startle are reduced by benzodiazepines, barbiturates and opiates. Advantages and disadvantages of these animal tests of anxiety are discussed. PMID- 2203069 TI - The psychopharmacology of 5-HT3 receptors. AB - The review presents evidence that 5-HT3 receptors within the brain may contribute to the control of behavior. 5-HT3 receptor antagonists GR38032F, zacopride, ICS 205-930 and other agents are very potent in reducing mesolimbic dopamine hyperactivity caused by the injection of amphetamine or infusion of dopamine into the rat nucleus accumbens and amygdala, and the ventral striatum of the marmoset. Such actions are distinguished from those of neuroleptic agents by a failure to reduce normal levels of activity or to induce a rebound hyperactivity after discontinuation of treatment. Indeed, the 5-HT3 receptor antagonists can prevent the neuroleptic-induced rebound hyperactivity. Further evidence that 5-HT3 receptors moderate limbic dopamine function is shown by their ability to reduce both the behavioral hyperactivity and changes in limbic dopamine metabolism caused by DiMe-C7 injection into the ventral tegmental area. The 5-HT3 receptor antagonists also have an anxiolytic profile in the social interaction test in the rat, the light/dark exploration test in the mouse, the marmoset human threat test and behavioral observations in the cynomolgus monkey. They differ from the benzodiazepines by an absence of effect in the rat water lick conflict test and a withdrawal syndrome. Importantly, the 5-HT3 receptor antagonists are highly effective to prevent the behavioral syndrome following withdrawal from treatment with diazepam, nicotine, cocaine and alcohol. Intracerebral injection techniques in the mouse indicate that the dorsal raphe nucleus and amygdala may be important sites of 5-HT3 receptor antagonist action to inhibit aversive behavior. Studies with GR38032F indicate an additional effect in reducing alcohol consumption in the marmoset. The identification and distribution of 5-HT3 receptors in the brain using a number of 5-HT3 receptor ligands, [3H]65630, [3H]zacopride and [3H]ICS 205-930 correlates between studies, and the 5-HT3 recognition sites in cortical, limbic and other areas meet the criteria for 5-HT3 receptors to mediate the above behavioral effects. Thus the use of 5-HT3 receptor antagonists reveals an important role for 5-hydroxytryptamine in the control of disturbed behavior in the absence of effect on normal behavior. The profile of action of the 5-HT3 receptor antagonists has generated a major clinical interest in their potential use for schizophrenia, anxiety and in the control of drug abuse. PMID- 2203070 TI - Endocrine pathology of estrogens: species differences. AB - The clinical uses of estrogens are associated with serious adverse effects, so the experimental toxicology of these compounds is under continuous review. Structurally different estrogens have qualitatively similar effects in animals when given in amounts way above the rodent uterotrophic dose. Toxicity still tends, however, to be related to estrogenic potency. Carnivores are more susceptible than rodents. Changes in reproductive, mammary and endocrine tissues are consistent with hyperestrogenism. Growth rate is decreased in rats and mice, but weight gains have been reported in other species. The weights of the liver, spleen, thymus and other organs are changed. Liver damage can occur. Susceptibility declines in the order cat, ferret, rat and mouse, dog. Clotting changes seen in the rat are secondary to liver damage. Moderate doses elicit anemia in rats, but lethal bone marrow depression in dogs and ferrets. Death is associated with hemorrhage. Antiestrogens modify aspects of estrogen toxicity in the rat, but not in the ferret. The predictive value of animal studies for humans has been disappointing. Interspecies variations at the hypothalamic-pituitary axis appear to have an important bearing on the differential activities of estrogens and antiestrogens across the species. PMID- 2203071 TI - Doxorubicin (adriamycin): a critical review of free radical-dependent mechanisms of cytotoxicity. AB - The antineoplastic drug doxorubicin is capable of generating a variety of free radical species in subcellular systems and this capacity has been considered critical for its antitumor action. However, for most tumor cell lines this mechanism of cytotoxicity does not appear to play a major role. Free radical independent cytotoxicity mechanisms, taking place in the nuclear compartment of the cell, may more likely be involved in the antitumor effect of doxorubicin. PMID- 2203072 TI - Hepatic circulation: potential for therapeutic intervention. AB - In recent years, knowledge of the physiology and pharmacology of hepatic circulation has grown rapidly. Liver microcirculation has a unique design that allows very efficient exchange processes between plasma and liver cells, even when severe constraints are imposed upon the system, i.e. in stressful situations. Furthermore, it has been recognized recently that sinusoids and their associated cells can no longer be considered only as passive structures ensuring the dispersion of molecules in the liver, but represent a very sophisticated network that protects and regulates parenchymal cells through a variety of mediators. Finally, vascular abnormalities are a prominent feature of a number of liver pathological processes, including cirrhosis and liver cell necrosis whether induced by alcohol, ischemia, endotoxins, virus or chemicals. Although it is not clear whether vascular lesions can be the primary events that lead to hepatocyte injury, the main interest of these findings is that liver microcirculation could represent a potential target for drug action in these conditions. PMID- 2203073 TI - On the pharmacology of bromelain: an update with special regard to animal studies on dose-dependent effects. AB - Bromelain, a standardized complex of proteases from the pineapple plant, is absorbed unchanged from the intestine of animals at a rate of 40%; in animal experiments it was found to have primarily anti-edema, antiinflammatory, and coagulation-inhibiting effects. These effects are due to an enhancement of the serum fibrinolytic activity and inhibition of the fibrinogen synthesis, as well as a direct degradation of fibrin and fibrinogen. Bromelain lowers kininogen and bradykinin serum and tissue levels and has an influence on prostaglandin synthesis, thus acting antiinflammatory. In in vitro and in animal studies, experimentally induced tumours could be inhibited by bromelain. Although many studies do not give extensive statistical data, the effects of bromelain in animal studies seem to be dose-dependent. Further investigations have to be carried out. PMID- 2203074 TI - [Prevention of friction loss of combination restorations]. PMID- 2203075 TI - [Preparation of a fireproof stump and fixation in the articulator]. PMID- 2203076 TI - [Ludwig's technic. 3. Functional impressions and registration]. PMID- 2203077 TI - [Ludwig's technic. 5. Set-up of prosthesis using Ludwigs' technic Calotte]. PMID- 2203078 TI - [Bonding of model casting of TeKo-Steg with ceramic-metal conical crown]. PMID- 2203079 TI - [Suggestion for sagittal adjustment of bonded bridges]. PMID- 2203080 TI - [Imitating crown forms with computer graphics]. PMID- 2203081 TI - [Ludwig's technic. 6. Physiological functional prosthesis (1)]. PMID- 2203082 TI - [Injection technic without gallium and beryllium]. PMID- 2203083 TI - [Rocatec system. Only another bonding system or a significant supplementary system?]. PMID- 2203084 TI - [Function and preparation of active interceptive orthodontic appliances]. PMID- 2203086 TI - [Ludwig's technic. 6. Physiological functional prostheses (2)]. PMID- 2203085 TI - [Preparation of a porcelain inlay]. PMID- 2203087 TI - [Working with pre-finished precision attachment elements in the adhesive technic]. PMID- 2203088 TI - [One-point technic. Technical advice for cost and time saving finishing of composite inlays by indirect methods]. PMID- 2203089 TI - [Finishing of plastic prostheses using Looping System--development of special cuvette for higher accuracy of fit by handling of poured plastic]. PMID- 2203090 TI - [Adaptation of completely dentulous subjects to various designs of palatal coverage]. PMID- 2203091 TI - [Characterization of metal/ceramic bonds using ISO and DIN bending tests]. PMID- 2203092 TI - [Plasma stream for bonding in dentistry]. PMID- 2203093 TI - Neurons, numbers and the hippocampal network. AB - Anatomists involved with studies of the hippocampal formation are being prodded by computational modelers and physiologists who demand detailed and quantitative information concerning hippocampal neurons and circuits. The beautiful camera lucida drawings of old, and the elegant descriptions of dendritic form that accompanied them are giving way to computer-reconstructed and three-dimensionally analyzed cells with rigorous determination of dendritic lengths and volumes, branching pattern and spine distribution. We will review certain quantitative aspects of hippocampal organization in the rat based on a survey of available literature and on our own intracellular labeling studies of granule cells of the dentate gyrus and pyramidal cells of the hippocampus. Some of the potential implications of these data for hippocampal information processing will be discussed. PMID- 2203094 TI - Understanding the brain through the hippocampus. The hippocampal region as a model for studying brain structure and function. Dedicated to Professor Theodor W. Blackstad on the occasion of his 65th anniversary. PMID- 2203095 TI - Stereological studies of the hippocampus: a comparison of the hippocampal subdivisions of diverse species including hedgehogs, laboratory rodents, wild mice and men. AB - The volumes of the fascia dentata, hilus, regio inferior, regio superior and subiculum of 9 species that differ significantly in size and degree of forebrain evolution have been compared with the intent of identifying phylogenetic trends in the internal organization of the mammalian hippocampus. The study includes data from the hippocampi of a basal insectivore, 2 species of wild mice, 3 commonly used laboratory rodents and 3 species (including man) that resemble an ascending primate series. In addition to comparisons of the absolute and relative volumes, an allometric approach is used to identify "progressive" size differences not related to body size. Both regio superior and hilus become larger during evolution, while fascia dentata and regio inferior maintain a relationship to body size that is similar to that for the hippocampus in basal insectivores. The inter-species differences are discussed in terms of neuron number and size, for which data are presented from two species, and with reference to a neural model of the cognitive map theory for hippocampal function. Special emphasis is placed on the unique aspects of the human hippocampus. The data represents a quantitative morphological framework within which the observations from physiological, biochemical and behavioral studies in laboratory animals can be related to studies of the human hippocampus. PMID- 2203096 TI - Membrane currents in hippocampal neurons. AB - This chapter reviews properties and functions of endogenous ionic currents in hippocampal neurones. Currents considered are: Na currents INa(fast) and INa(slow); Ca currents; K currents--delayed rectifier IK(DR), transient IK(A), 'delay' current IK(D) and M current IK(M); inward rectifiers IQ, IK(IR) and ICl(V); Ca-activated currents IK(Ca) (IC and IAHP), ICl(Ca) and Ication(Ca); Na activated currents; and anoxia-induced currents. PMID- 2203097 TI - Potassium currents in hippocampal pyramidal cells. AB - The hippocampal pyramidal cells provide an example of how multiple potassium (K) currents co-exist and function in central mammalian neurones. The data come from CA1 and CA3 neurones in hippocampal slices, cell cultures and acutely dissociated cells from rats and guinea-pigs. Six voltage- or calcium(Ca)-dependent K currents have so far been described in CA1 pyramidal cells in slices. Four of them (IA, ID, IK, IM) are activated by depolarization alone; the two others (IC, IAHP) are activated by voltage-dependent influx of Ca ions (IC may be both Ca- and voltage gated). In addition, a transient Ca-dependent K current (ICT) has been described in certain preparations, but it is not yet clear whether it is distinct from IC and IA. (1) IA activates fast (within 10 ms) and inactivates rapidly (time constant typically 15-50 ms) at potentials positive to -60 mV; it probably contributes to early spike-repolarization, it can delay the first spike for about 0.1 s, and may regulate repetitive firing. (2) ID activates within about 20 ms but inactivates slowly (seconds) below the spike threshold (-90 to -60 mV), causing a long delay (0.5-5 s) in the onset of firing. Due to its slow recovery from inactivation (seconds), separate depolarizing inputs can be "integrated". ID probably also participates in spike repolarization. (3) IK activates slowly (time constant, tau, 20-60 ms) in response to depolarizations positive to -40 mV and inactivates (tau about 5s) at -80 to -40 mV; it probably participates in spike repolarization. (4) IM activates slowly (tau about 50 ms) positive to -60 mV and does not inactivate; it tends to attenuate excitatory inputs, it reduces the firing rate during maintained depolarization (adaptation) and contributes to the medium after-hyperpolarization (mAHP); IM is suppressed by acetylcholine (via muscarinic receptors), but may be enhanced by somatostatin. (5) IC is activated by influx of Ca ions during the action potential and is thought to cause the final spike repolarization and the fast AHP (although ICT may be involved). Like IM, it also contributes to the medium AHP and early adaptation. It differs from IAHP by being sensitive to tetraethylammonium (TEA, 1 mM), but insensitive to noradrenaline and muscarine. Large-conductance (BK; about 200 pS) Ca-activated K channels, which may mediate IC, have been recorded. (6) IAHP is slowly activated by Ca-influx during action potentials, causing spike-frequency adaptation and the slow AHP. Thus, IAHP exerts a strong negative feedback control of discharge activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2203098 TI - Cytosolic free calcium in hippocampal CA3 pyramidal cells. AB - The dynamics of cytosolic free Ca2+ ([Ca2+]i) of single voltage-clamped CA3 pyramidal cells in hippocampal slice cultures is reviewed. [Ca2+]i amounts to about 30 nM at resting membrane potential and increases slowly when the membrane potential is clamped at more positive values (up to 500 nM at -30 mV). Short lasting depolarizations (40-100 ms) induce a transient rise in [Ca2+]i which activates a slow aftercurrent (IAHP). The muscarinic or beta-adrenergic depression of IAHP is not accompanied by any change in the dynamics of Ca2+ and appears, therefore, to result primarily from an inhibition of the K(+)-current itself or of the ability of Ca2+ to activate the current. At higher concentrations than those required to inhibit IAHP, muscarine produces a pronounced inward current and this is accompanied by a rise in resting [Ca2+]i concentration. PMID- 2203099 TI - Long-term potentiation in the hippocampal CA1 region: its induction and early temporal development. AB - Long-term potentiation (LTP) is a process that due to its prolonged time course and associative nature of induction is believed to be involved in learning and memory in the mammalian brain. In this chapter the experimental evidence for the view that LTP is initiated by an influx of calcium ions through synaptically controlled N-methyl-D-aspartate (NMDA) receptor channels is discussed. It will also be described how LTP develops following its induction. It will be shown that there is a considerable delay, about 2-3 s, between a tetanus and the initiation of LTP, and that additional 20-30 s are needed for the potentiation to reach peak levels. The potentiation subsequently decays to a degree which depends primarily on tetanus length. It will be argued that this early phase of tetanus-induced LTP is of the same nature as that present a few hours later. PMID- 2203100 TI - Spatial organization of physiological activity in the hippocampal region: relevance to memory formation. AB - Based on a review of anatomical and physiological findings, we suggest that the hippocampus may be viewed as a positive feedback device (autoassociator), which is capable of modifying the activity of the neocortical neurons. We examine the three-dimensional organization of evoked and spontaneous physiological patterns of the hippocampus and suggest rules how these patterns emerge during different behaviors from a hard-wired structural network. The high spatial coherence of theta activity is due to an external pacemaker, while the high synchrony of population bursts underlying hippocampal sharp waves is explained by the similar probability of recruitment of neurons by the burst-initiator cells along the whole extent of the hippocampus. We suggest that the burst-initiator cells are a group of CA3 neurons whose excitability is increased by a transient potentiation action of the neocortical activity during theta-concurrent exploratory behaviors. We hypothesize that sharp wave-concurrent population bursts result in a highly synchronous hippocampal output, converging preferentially on those entorhinal neurons which were instrumental in the creation of the burst-initiator neurons. The feedback action of population activity thus provides a selective mechanism for potentiation of connections between information-carrying neurons in the hippocampus and entorhinal cortex. The state-dependent operations of the anatomical hardware also point to the importance and advantage of studying the physiological activity of the intact brain. PMID- 2203101 TI - A computational theory of the hippocampal cognitive map. AB - Evidence from single unit and lesion studies suggests that the hippocampal formation acts as a spatial or cognitive map (O'Keefe and Nadel, 1978). In this chapter, I summarise some of the unit recording data and then outline the most recent computational version of the cognitive map theory. The novel aspects of the present version of the theory are that it identifies two allocentric parameters, the centroid and the eccentricity, which can be calculated from the array of cues in an environment and which can serve as the bases for an allocentric polar co-ordinate system. Computations within this framework enable the animal to identify its location within an environment, to predict the location which will be reached as a result of any specific movement from that location, and conversely, to calculate the spatial transformation necessary to go from the current location to a desired location. Aspects of the model are identified with the information provided by cells in the hippocampus and dorsal presubiculum. The hippocampal place cells are involved in the calculation of the centroid and the presubicular direction cells in the calculation of the eccentricity. PMID- 2203102 TI - NGF-dependent sprouting and regeneration in the hippocampus. AB - While a variety of sprouting and regenerative responses have been investigated in the hippocampus, the cellular and molecular events responsible for these plastic responses have not been determined. One transmitter system, the cholinergic system, shows several distinct responses to damage in the septohippocampal circuit. Present evidence strongly supports a role for nerve growth factor (NGF) in these responses. NGF is not only important for the survival of the adult cholinergic neurons, but can also induce regrowth of the damaged fibers given an appropriate substratum for growth. These reparative effects of NGF can manifest themselves in functional recovery in the aged rat and the young rat with fimbria fornix lesions. Finally, a role for glia cells is proposed to clarify how NGF availability may be regulated during the degenerative and regenerative events. While all plasticity events certainly cannot be explained by the coincidence of NGF and the cholinergic system, their interaction may provide a template for other transmitter/trophic factor interactions. PMID- 2203103 TI - Two different ways evolution makes neurons larger. AB - As evolution makes larger brains it also increases the size of many of the individual neurons that make up the brain. How neurons are made larger can give clues about design principles of the brain's circuits. One way of making a larger neuron is called conservative scaling. If evolution magnifies a particular type of neuron by a factor of two-that is, each dendrite is made twice as long-then the neuron is scaled conservatively if the magnified neuron has dendrites with 4 times the diameter of their unscaled counterparts. This type of scaling leaves the passive cable properties of the neuron unchanged and so maintains a balance in effectiveness between proximal and distal dendritic inputs. One might imagine that, for some types of circuits, maintaining such a balance would be necessary to use just the same neuronal interconnections in both large and small brains. We have compared dentate granule cells and CA1 pyramidal neurons in cat and human to establish how these cell types are, in fact, scaled. Both cell types are larger in human than in cat, even though their general form is conserved. Pyramidal neurons scale conservatively, but dentate granule cells do not. The CA1 circuits seem, then, to require conservation of the passive cable properties of their elements, whereas dentate does not. We suggest that the reason CA1 neurons scale conservatively is that, for this region, each individual synaptic input exerts a significant effect on the cell's output, whereas in dentate the neuronal output represents the average of a large number of anonymous individual inputs. PMID- 2203104 TI - Seizures, neuropeptide regulation, and mRNA expression in the hippocampus. AB - Recent studies have demonstrated that the regulation of neuropeptide expression in forebrain neurons is responsive to external influences including changes in physiological activity. This has been demonstrated most clearly in studies of hippocampus where the synthesis and resting levels of several neuropeptides, localized within well-characterized components of hippocampal circuitry, have been shown to be selectively influenced by seizure activity. In studies described here, we examined the influence of recurrent limbic seizures on the expression of enkephalin, dynorphin, cholecystokinin, and neuropeptide Y (NPY) in rat and mouse hippocampus using immunohistochemical, in situ hybridization and blot hybridization techniques. The data demonstrate that seizures differentially influence the expression of each peptide as a part of a broader cascade of changes in genomic expression within individual hippocampal neurons. In particular, seizures increase preproenkephalin mRNA and enkephalin peptide but decrease dynorphin peptide in the dentate gyrus granule cell/mossy fiber system. Seizure-induced decreases in the concentration of preprodynorphin mRNA in the granule cells have been reported by others. Immunoreactivity for CCK, which is codistributed with the opioid peptides in the mossy fiber system of mouse, is also dramatically reduced in the granule cell axons by seizure. Recurrent seizures induce two temporally distinct changes in NPY expression in hippocampus. First, there is an increase in hybridization to preproNPY mRNA within scattered, probable local circuit neurons in all subfields. This is followed by the seemingly novel appearance of preproNPY mRNA within the dentate gyrus granule cells and pyramidal cells of field CA1. Clues about mechanisms of neuropeptide regulation have come from observations of other, more rapid, transcriptional events induced by seizure. Most notably, our results and those of others demonstrate that seizures increase the expression of messenger RNAs from immediate-early genes (c-fos, c-jun, and NGFI-A) which encode proteins that may mediate neuropeptide gene regulation. In addition, mRNA for nerve growth factor is dramatically increased in the dentate gyrus granule cells by seizure; increased production of this trophic factor might mediate the more delayed changes in genomic expression and growth responses observed to occur in hippocampus and other forebrain areas following seizure activity. PMID- 2203105 TI - Reafferentation of the subcortically denervated hippocampus as a model for transplant-induced functional recovery in the CNS. AB - Subcortical deafferentation of the hippocampal formation is known to induce profound behavioural deficits. Transplants of fetal septal or brainstem tissue are capable of restoring some aspects of normal physiological and behavioural function in subcortically deafferented (i.e. fimbria-fornix or septal lesioned) rats. Such grafts have been shown to re-establish extensive new afferent inputs to the denervated hippocampal formation. As shown for grafted cholinergic and noradrenergic neurons, the ingrowing axons form laminar innervation patterns which closely mimic those of the normal cholinergic and noradrenergic innervations. The ingrowth appears to be very precisely regulated by the denervated target: each neuron type produces distinctly different innervation patterns; the growth is inhibited by the presence of an intact innervation of the same type; and it is stimulated by additional denervating lesions. Both ultrastructually and electrophysiologically the graft-derived fibres have been seen to form extensive functional synaptic contacts. Biochemically, cholinergic septal grafts and noradrenergic locus coeruleus grafts restore transmitter synthesis and turnover in the reinnervated hippocampus. Intracerebral microdialysis has revealed that acetylcholine and noradrenaline release is restored to normal or supranormal levels in the graft-reinnervated hippocampus, and that the grafted neurons can be activated in a normal way from the host through behavioural activation induced by sensory stimulation or electrical stimulation of the lateral habenula. These results indicate that the grafted monoaminergic neurons can restore tonic regulatory neurotransmission at previously denervated synaptic sites even when they are implanted into the ectopic brain sites. Such functional reafferentation may be sufficient for at least partial restoration of function in the subcortically deafferented hippocampus. PMID- 2203106 TI - Axon sprouting in the rodent and Alzheimer's disease brain: a reactivation of developmental mechanisms? AB - Research over the past 15 years has led to a comprehensive description of the processes of axonal sprouting and synaptic reorganization in the hippocampus. Previous studies on axonal sprouting have now been supplemented with recent studies on excitatory amino acid receptor plasticity. These and related studies pave the way to research strategies which detail the molecular mechanisms of the sprouting response. The re-expression of the fetal form of alpha-tubulin mRNA in rat after entorhinal lesions was found to be similar to the re-expression of the human fetal form of alpha-tubulin in Alzheimer's brain. This result suggests that the sprouting process may involve a reactivation of certain developmental mechanisms and that this may possibly contribute to the etiology of Alzheimer's disease. PMID- 2203108 TI - Zinc-containing neurons in hippocampus and related CNS structures. AB - Recent advances in metallohistochemistry have substantiated the identification of a distinct class of neurons in the brain, the zinc-containing neurons. These neurons sequester peculiar amounts of zinc in their presynaptic boutons and show both high-affinity uptake and calcium- and impulse-dependent release of the cation. It is thought that the zinc may act to stabilize the storage of certain macromolecules in presynaptic vesicles, but there is also mounting evidence that zinc released from vesicles can produce a broad spectrum of neuromodulatory effects upon target cells. Zinc-containing neurons are found predominantly in limbic and cerebrocortical regions, and a possible role of these neurons in the modification of synaptic strength is considered. PMID- 2203107 TI - Hippocampal plasticity in normal aging and decreased plasticity in Alzheimer's disease. AB - Different patterns of age-related dendritic change have been reported in different zones of the human hippocampal region in the normal and Alzheimer's disease (AD) brain. In normal aging there is an increase in average (net) dendritic extent (which we interpret as plasticity) in the parahippocampal gyrus and dentate gyrus. There is net stability of dendritic extent in CA2-3, CA1, and subiculum. In regions that show plasticity in normal aging, dendrites in AD show reduced or aberrant plasticity. In regions that show stability in normal aging, dendrites either are stable or regress in AD, depending upon how severely involved the region is with the pathology of AD. PMID- 2203109 TI - Cardiac xenotransplantation. PMID- 2203110 TI - The lipid hypothesis and the role of hemodynamics in atherogenesis. PMID- 2203111 TI - Myocardial and pulmonary protection: long-distance transport. PMID- 2203112 TI - Clinical results of heart and heart-lung transplantation. PMID- 2203113 TI - [Real-time sonography in the evaluation of peri- and intraventricular cerebral hemorrhage]. AB - Of 1776 sonograms done on 1312 patients with sector real time equipment, 923 done on 670 patients were selected because of suspected peri and intraventricular cerebral hemorrhage. The studies demonstrated hemorrhage in only 117 patients. It was possible to follow 107 patients and in 6.8 the hemorrhage was grade I, in 14 children it was grade II, in 19 it was grade II and in 6 it was grade IV. Most of the children (82 of 107) were pre-term (the average gestational age was less than 32 weeks). Twenty-three were term and two were post term. In most instances, the grade I hemorrhage resolved without sonographic or neurological sequelae, but in ten patients the hemorrhagic focus was replaced by a "cyst" which resolved in seven to more than 204 days; and in two it was replaced by a porencephalic cyst, which in one of the patients could still be seen at 134 days (when the last study was performed). All patients with grade II hemorrhage were pre-term (average gestational age of 33.1 weeks). Sonographic follow-up of these patients showed that hemorrhagic foci were not visible after 84 days (time of the last sonogram) and that only two children had slight hydrocephaly. Most of the children with grade III hemorrhage (75%) were premature (average gestational age of 32 weeks), and the others (25%) were at term. This was the group in which the greatest number of sonographic sequelae (e.g. hydrocephaly and/or atrophy) were observed. Also in this group more serious neurological sequelae were found. Grade IV Hemorrhage was found in the smallest number of patients but it had the worst prognosis: 2 of 2 premature babies died; 1 of 3 term babies died at 14 days after birth, another develop hydrocephaly and was operated on (developed cerebral palsy) and the third one was lost to follow up. A post term child with grade IV hemorrhage is being followed in the high risk clinic (at 10 months she has neurological sequelae which are not severe). At times it is difficult to differentiate grade IV hemorrhage from other conditions such as leukomalacia and/or peri-ventricular infarct. Real time sonography, performed through the anterior fontanelle has been shown to be very useful in the diagnosis and follow up of peri and intraventricular cerebral hemorrhage. PMID- 2203114 TI - [Genetic and epidemiologic aspects in diabetes mellitus]. AB - Epidemiology and genetics go hand in hand in Diabetes, confirming and providing clinical bases foreseen by our predecessors. They provide more solid scientific bases to search for markers that will allow us to detect susceptible populations earlier and thus eliminate or correct risk factors. We may be able to select the subjects at greater risk, for appropriate pre-marital and gestational counseling. This is a wide and promising field for investigation that will result in better prevention and diagnosis, as well as in improved therapy and prognosis. PMID- 2203115 TI - [Sweet's syndrome. A study of 10 cases and review of the literature]. AB - Ten cases of acute febrile neutrophilic dermatosis or Sweet's disease have been studied clinically and histologically. Seventy percent of the patients were females with mean age of 43.1 +/-9 years. All of them presented the typical skin lesions consisting of papules and painful erythematous--edematous plaques in face, neck and upper chest. Fever was observed in seven patients and painful joints in four cases. One case presented polyarthritis of the big joints and there was one other case of conjuntivitis. The analytical data revealed a constant increase in sedimentation rate observed in 90% of patients. Leukocytosis was observed in 30% of patients and neutrophilia in 40%. Histologically, the lesions showed a neutrophilic infiltration of the skin without signs of vasculitis. Eight patients received treatment with Prednisone per os, one of whom, because of his relapses, was later given Potassium Iodine. Another patient was treated with Indomethacin, and one patient did not received any treatment. The evolution was favorable in all cases with sustained remissions. Sweet's Syndrome has been described associated mainly with acute myeloid leukemia in 10 20% of patients and in isolated instances with other systemic and neoplasic diseases. The concomitant conditions in 50% of our cases were: Ulcerative colitis, nodular sclerotic Hodgkin disease, infiltrative ductal carcinoma of the breast, carcinoma of the uterus neck and Crohn's disease; these last two associations had not been previously described in the literature. PMID- 2203117 TI - [Buspirone: a new non-benzodiazepine anxiolytic drug]. AB - Buspirone is a new drug with ansiolitic properties which chemical structure and mechanism of action is different from the classical drugs traditionally used for this symptom. Its farmacokinetic characteristics make it a convenient drug to be used for oral administration. Buspirone's double-blind controlled clinical studies contrasted with benzodiazepines have shown that buspirone has an ansiolitic effect close to them but without sedation or relaxation. Other secondary effects appear with a smaller incidence with buspirone. These properties make buspirone very efficient in anxiety treatment. PMID- 2203116 TI - [Bilateral nodular hyperplasia of the adrenal glands; diagnostic problems]. AB - Bilateral adrenal nodular hyperplasia (BAND) is rarely presented as a cause of Cushing Syndrome. The pathogenicity of the disease is unknown and it does not present either symptoms or specific signs, furthermore, its steroid dynamic is atypical and the morphologic tests are not conclusive. The clinical stories of six BAND-diagnosed patients in our Department have been reviewed with the aim of unifying the criteria of the preoperative diagnosis with regard to treatment, comparing our results with literature's wider series. The results from both studies demonstrate an hypophyseal dependence together with some others showing a adrenal autonomy. Thus, our conclusions perpetuate the pathogenic question about BAND (whether is an adrenal primary disfunction or a secondary effect caused by hypophyseal ACTH hypersecretion?) and we point out the usefulness of radioisotopic gammagraphy and abdominal-TAC, since usually they show the bilaterality of the injury at adrenal level. PMID- 2203118 TI - [General considerations on the pathogenesis of porphyria]. PMID- 2203119 TI - [Toxic megacolon and intestinal perforation caused by Salmonella enteritidis]. AB - Two cases of colitis due to Salmonella enteriditis which later developed a toxic megacolon with intestinal perforation are presented and the probable pathogenesis is discussed. This exceptional clinical course which has not been previously described forces to perform a differential diagnosis with chronic intestinal inflammatory disease which must be based on microbiologic, serologic and/or histologic criteria. Moreover, the authors warn about the unsuitability of using anticholigernic drugs in gastroenteritis since they could be related to the ethiopathogenical basis of the disease's unfavorable course in the described patients. PMID- 2203120 TI - [3 cases of diffuse lymphangioleiomyomatosis of the lung]. AB - Three new cases of diffuse pulmonary lymphangioleiomyomatosis are presented. Case number 1 is a female patient who presented repeated pneumotorax and dyspnea without evidence by CT scan and gynecological ultrasound of extrathoracic lesions. This patient did not respond to medroxiprogesterone and died 5 years after the initial diagnosis having suffered chronic, severe, global respiratory failure for 4 years. Case number 2 is a female patient who presented dyspnea, chyloptysis and chylothorax, with iliac, paraaortic and mediastinic lymphangioleiomyomas. The last time she was seen, she was still alive after 6 years without treatment. Case number 3 presented lymphangioleiomyomatosis associated to undifferentiated breast carcinoma. The evolution was apparently slow probably because it was diagnosed 14 years after menopause, and died due to a relapse of the neoplasia. All three patients had radiographic images and respiratory functional studies characteristic of this disease and diagnosis was confirmed by biopsy. The literature is reviewed. PMID- 2203121 TI - [Cough secondary to the use of captopril. An adverse effect more and more frequent]. PMID- 2203122 TI - [Diagnosis and treatment of lesions of the tricuspid valve: an unresolved problem]. PMID- 2203123 TI - [Pericardial tamponade and systemic sclerosis]. AB - We report a case with systemic sclerosis (scleroderma) presented with an acute pericarditis and pericardial tamponade with haemodynamic impairment that required pericardial drain. The frequency of pericardial disease in scleroderma is high, but the clinical recognition is rare, and tamponade with haemodynamic impairment requiring aspiration for relief is exceptional, but should be considered in patients with scleroderma that present an acute pericarditis. It is suggested that pericardial fibrosis in scleroderma may predispose to pericardial tamponade. PMID- 2203124 TI - A chimera antibody erythroimmunoassay for detecting HBsAg in human sera. AB - A highly efficient chimera antibody, a monoclonal anti-hepatitis-B-surface (anti HBs) antibody coupled with polyclonal anti-sheep-red-blood-cell (anti-SRBC) antibody was prepared using a heterobifunctional reagent, N-succinimidyl-3-(2 pyridyldithiopropionate) (SPDP). Using SRBC as a marker, we established a sensitive solid-phase chimera antibody erythroimmunoassay (CAEIA) according to Guesdon's method. The sensitivity of this assay was 2-20 times higher than the reverse passive haemagglutination assay (RPHA) for detecting HBsAg in serially diluted sera from 10 hepatitis B patients. The weakest quantity of HBsAg detected by this assay was 4.5 ng/ml, while RPHA was unable to detect less than 75 ng/ml of HBsAg. The assay was as sensitive as the enzyme-linked immunosorbent assay (ELISA) and gave more accurate, reproducible and stable results than ELISA; specificity was also satisfactory. PMID- 2203125 TI - Sensitive enzyme immunoassay for the rapid diagnosis of influenza A virus infections in clinical specimens. AB - Samples of nasopharyngeal secretion (NPS) from 100 infants and small children admitted for acute respiratory disease during the period from January to March 1989 were examined for the presence of influenza A virus. All samples were tested by enzyme immunoassay (EIA), fluorescent antibody (FA) technique and by isolation in cell culture 3-6 h after they were obtained from the patients. Of 24 influenza strains found by isolation, 21 were detected by EIA and 19 were FA+. In comparison with virus isolation, EIA gave the following values: sensitivity 88%, specificity 100%, positive prognostic value (PPV) 100%, and negative prognostic value (NPV) 96%. A rabbit anti-influenza-A serum (A-13) was used as catching antibody and a monoclonal anti-influenza-A pool against NP protein was used as detector antibody in EIA. A-13 gave bands corresponding to influenza A core proteins (NP and M1) in Western blot (WB) studies when different H3N2 strains were employed as antigens. A-13 gave only a band corresponding to the NP protein when H1N1 strains were examined by WB. The detection level by EIA for both H3N2 and H1N1 strains precipitated by polyethylene glycol from tissue culture maintenance medium was 1-2 ng. PMID- 2203126 TI - A review and critique of psychological approaches to the burn-out phenomenon. AB - In the 70s the concept burn-out appeared in psychological literature on the helping professions. The concept has since then been ascribed several meanings, and critical voices have been raised against the lack of clarity and consensus in the definitions. The aim of this article was to critically examine the thinking on the concept of burn-out. The helping professionals--nurses, welfare officers, psychologists, medical doctors, etc.--have expanded rapidly since the 60s. It is stated that the issues on which burn-out researchers focus deserve the attention of social scientists in general. The major limitation in the literature on burn out is that there is little analysis of the role of society and social conditions in producing the phenomenon. It is suggested that sociological analyses may have a contribution to make here. PMID- 2203127 TI - [Dihydroergotamine as a nasal spray in the therapy of migraine attacks. Efficacy and tolerance]. AB - In an open multicentre study in Switzerland, the dihydroergotamine nasal spray was studied for its efficacy and tolerability in the treatment of acute migraine attacks (common and classical migraine--one attack each patient) in a total of 904 patients. In the global assessment, 76.8% of all the patients reported good efficacy (freedom from pain, less pain or shorter duration of pain). When the nasal spray was used already in the prodromal phase, good efficacy could be obtained by 90 (63%) of 143 patients. 18.1% of all the patients treated--more frequently those who obtained no beneficial effect and/or who took additional medication during the migraine attack--reported one or more--minor side-effects such as local nasal irritation (congestion, burning or stinging), nausea, dizziness and vomiting. 3.9% of the patients said they would not use the spray again because of the side effects. PMID- 2203128 TI - [Visceral leishmaniasis as an opportunistic infection. Case report and literature review]. AB - With increasing numbers of immunocompromised patients a rise in the incidence of visceral leishmaniasis has to be expected. Presenting a case of visceral leishmaniasis in an HIV-infected patient and reviewing the literature, we discuss general aspects of this parasitic disease and special features of it as an opportunistic infection. PMID- 2203129 TI - The highly resorbed, fully edentulous case: implant supported full dentures add vitality to the removable restorative field. PMID- 2203131 TI - Esthetics, complete dentures and facial muscles. PMID- 2203130 TI - Use of the Steri-Oss PME abutment with a bar-retained overdenture. PMID- 2203132 TI - Porcelain failure and improper framework design. PMID- 2203133 TI - Implants using light cure composite. PMID- 2203134 TI - Heterogeneity of RNP and Sm autoantigens in relation to the cell sources and the activated state of the cells. AB - The extracts of rabbit thymus (RTE), HeLa cells, human histiocytic lymphoma cell line U-937, human promyelocytic cell line HL-60, Ehrlich ascites tumor cells (EACs), and peripheral white blood cells (WBCs) were tested for their composition, molecular weight, and amount of Sm and RNP autoantigens on immunoblotting. The molecular weight of the so-called 68 kDa U1 RNP antigen, which is associated with mixed connective tissue disease (MCTD), was 64.5 kDa in RTE, 62.5 kDa in HeLa cells and HL-60 cells, and 59 kDa in WBCs. Surprisingly, in both WBCs and U-937 cells, the main protein band bearing the 68 kDa U1 RNP antigenic determinants was 30.5 kDa in molecular weight, which was confirmed using antibodies purified by affinity chromatography. After stimulation with phytohemagglutinin (PHA), there was in the human lymphocytes a diminished amount of the 30.5 kDa protein and simultaneously an increased synthesis of several proteins of higher molecular weight, especially the 57 kDa protein bearing the 68 kDa antigenic determinants. The concentrations of the A, B/B', C, D, and E proteins also increased with PHA stimulation. Our results indicate that the expression of Sm and RNP autoantigens may depend on the cell source as well as the activated state of cells. These differences should be taken into consideration in the detection of anti-RNP and anti-Sm antibodies by immunoblotting. PMID- 2203135 TI - Colony stimulating factor occurs in both inflammatory and noninflammatory synovial fluids. AB - Synovial fluids (SF) from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) and various other arthritides were examined for the presence of colony stimulating factors (CSF). CSF was found in 7 of 13 (54%) SF from OA patients and in 8 of 12 (67%) SF from RA patients. It was also found in SF from patients with other arthropathies including 5 of 5 samples from patients with septic arthritis. Inhibition studies employing monospecific antisera indicated that in both RA and OA, CSF was of the macrophage type (M-CSF). While CSF was found in both inflammatory and noninflammatory effusions, significantly greater numbers of colonies were stimulated by RA SF than by OA SF and in general greater numbers of colonies correlated with higher SF leukocyte counts. Our data suggest that CSF as well as other cytokines may be involved in the perpetuation of joint destruction that occurs in various rheumatological conditions. PMID- 2203136 TI - Ultrasonography of the elbow joint. AB - The nonechogenic space between the bone and the joint capsule was measured in ultrasonographic scans at six different sites in 60 elbow joints of 30 healthy adults as well as in 35 joints with clinical arthritis. The space could be demonstrated in all healthy joints on the volar side at the levels of the trochlea and the capitulum of the humerus. The space was more than 2 mm in three out of the 60 healthy joints at these levels, and the space did not increase in 30 degrees flexion of the joint. The means of the measurements were significantly higher at all six sites in the arthritic joints than in the healthy joints and on the volar site the space increased in 30 degrees flexion of the arthritic joint. The space was more than 2 mm in all arthritic joints at the levels of either the trochlea or the capitulum of the humerus. An ultrasonographic distance of more than 2 mm on the volar side of the elbow joint between the joint capsule and the bone is with high probability a sign of intraarticular effusion or synovitis. The effusion in the olecranon fossa can also be demonstrated in all cases. PMID- 2203137 TI - The epidermal growth factor. A review of structural and functional relationships in the normal organism and in cancer cells. AB - The article is a review of recent knowledge of the structural relationships of epidermal growth factor (EGF) with other biological products occurring in a wide range of animal species and some viruses. The place of EGF and related products in the physiology of the whole organism is discussed against this background. Special attention is given to the role of EGF as a tissue growth factor and to the participation of related products in cancer. PMID- 2203138 TI - Development of gangrene during sleep. AB - A method for continuous measurement of subcutaneous adipose tissue blood flow in the forefoot over 24 h (SBF) is described. The method is based on the radioisotope wash-out principle using 133-Xenon (133Xe). A portable semiconductor detector is placed just above a local depot of 37-74 kBq 133Xe in 0.1 ml isotonic saline, injected into the subcutaneous adipose tissue in the forefoot. The detector is connected to a memory unit allowing for storage of data. Because of the short distance, the recorded elimination rate constant must be corrected for combined convection and diffusion of the radioactive indicator. Characteristic 24 h blood flow patterns were unveiled in patients with normal peripheral circulation and in patients having ischaemic nocturnal rest pain. In normal subjects, SBF doubled from day to night. This is ascribed to the local veno arteriolar sympathetic axon reflex, which induces vasoconstriction when the transmural pressure of the veins exceeds approximately 25 mmHg. In patients having ischaemic rest pains SBF was reduced by 37% on the average from day to night. This was caused by nocturnal hypotension, which is reflected proportionally in the foot. As the resistance vessels most probably are fully dilatated in feet with rest pain, the blood pressure drop during sleep causes the perfusion pressure and, therefore, blood flow to drop below a certain critical limit. There was a pronounced correlation between the reduction systemic mean arterial blood pressure and SBF. The patients complaining of intermittent claudication, but no rest pains, demonstrated a variety of changes in SBF compatible with the continuous spectrum of peripheral arteriosclerotic disease. The reduced blood flow during sleep in patients having ischaemic rest pains give rise to the concept of the development of gangrene during sleep. PMID- 2203139 TI - [The pathogenesis of multiple sclerosis]. AB - Genetic factors determine susceptibility to multiple sclerosis (MS), and environmental factors influence the clinical manifestations of the disease. In recently formed plaques the blood-brain barrier is open for about 6 weeks. Water content is increased in white matter appearing normal macroscopically and in cortex of MS patients. Activated T-lymphocytes accumulate and stimulate microglia and macrophages, which initiate the demyelinating process. In chronic plaques astroglial cells form a scar tissue around axons devoid of myelin. Modern imaging techniques make it possible to differentiate inflammation and demyelination in vivo. PMID- 2203140 TI - [Goals, results and limitations of multimodal tumor therapy]. AB - Multimodal tumor therapy, or the employment of two or more treatment modalities in combination, had led to several advances in the cure or long-term survival of patients with various tumor types. The individual established indications for multimodal tumor therapy are listed and described. Other indications remain controversial or are under evaluation in prospective randomized studies. In certain tumor types no advantage from the use of multimodal treatment has been demonstrated as yet. Aside from the advantages of multimodal therapy, the problems involved and possible side effects, especially in regard to short-, mid- and long-term toxic effects are described. PMID- 2203141 TI - [Adjuvant therapy in colorectal carcinoma]. AB - In Western industrialized countries colorectal adenocarcinoma is the second most common solid malignant tumor. Despite radical surgery in 75-80% of all cases, about 50% of the patients with colorectal carcinoma die of this tumor. The essential advances of recent years are reduction of the surgical complication rate and of postoperative mortality. Recent studies show that radiotherapy for rectum carcinoma and chemotherapy (5-fluorouracil in combination with levamisole) for colon carcinoma can be significantly helpful as an additional measure in certain subgroups. However, such so-called multimodality treatment concepts need adequate equipment and experience and should only be implemented, whenever possible, in controlled clinical trials. PMID- 2203142 TI - Bovine growth hormone: human food safety evaluation. AB - Scientists in the Food and Drug Administration (FDA), after reviewing the scientific literature and evaluating studies conducted by pharmaceutical companies, have concluded that the use of recombinant bovine growth hormone (rbGH) in dairy cattle presents no increased health risk to consumers. Bovine GH is not biologically active in humans, and oral toxicity studies have demonstrated that rbGH is not orally active in rats, a species responsive to parenterally administered bGH. Recombinant bGH treatment produces an increase in the concentration of insulin-like growth factor-I (IGF-I) in cow's milk. However, oral toxicity studies have shown that bovine IGF-I lacks oral activity in rats. Additionally, the concentration of IGF-I in milk of rbGH-treated cows is within the normal physiological range found in human breast milk, and IGF-I is denatured under conditions used to process cow's milk for infant formula. On the basis of estimates of the amount of protein absorbed intact in humans and the concentration of IGF-I in cow's milk during rbGH treatment, biologically significant levels of intact IGF-I would not be absorbed. PMID- 2203143 TI - Interphase and metaphase resolution of different distances within the human dystrophin gene. AB - Fluorescence in situ hybridization makes possible direct visualization of single sequences not only on chromosomes, but within decondensed interphase nuclei, providing a potentially powerful approach for high-resolution (1 Mb and below) gene mapping and the analysis of nuclear organization. Interphase mapping was able to extend the ability to resolve and order sequences up to two orders of magnitude beyond localization on banded or unbanded chromosomes. Sequences within the human dystrophin gene separated by less than 100 kb to 1 Mb were visually resolved at interphase by means of standard microscopy. In contrast, distances in the 1-Mb range could not be ordered on the metaphase chromosome length. Analysis of sequences 100 kb to 1 Mb apart indicates a strong correlation between interphase distance and linear DNA distance, which could facilitate a variety of gene-mapping efforts. Results estimate chromatin condensation up to 1 Mb and indicate a comparable condensation for different cell types prepared by different techniques. PMID- 2203144 TI - [Value of diagnostic measures in soft tissue diseases and soft tissue lesions of the shoulder joint]. AB - Calcifying tendinitis, acute tendinitis, frozen shoulder, rotator cuff rupture, subluxation of the gleno-humeral joint and injury of the biceps tendon are commonly classed under the blanket term "peri-arthropathy of the shoulder". It is now possible to make a precise diagnosis of these shoulder disorders by means of a clinical examination supported by X-ray examination, ultrasonography, arthrography, computed tomography (CT), magnetic resonance imaging (MRI) and arthroscopy. Calcifying tendinitis is diagnosed by consideration of the patient's history, followed by clinical examination and X-ray examination. Acute tendinitis is a clinical diagnosis, as is frozen shoulder. Ruptures of the rotator cuff can be detected by ultrasonography, which is a screening method; such ruptures can also be detected by arthrography. The localization and extent of the defect are best estimated by arthroscopy. Shoulder instability is another clinical diagnosis. Bony defects of the humeral head (Hill-Sachs lesion) or the glenoid rim are revealed by computed tomography (CT). CT arthrography reveals the presence of any Broca-Hartman lesion in the anterior inferior part of the anterior capsular mechanism. Rupture, subluxation or luxation of the biceps tendon are diagnosed either by clinical examination or by arthroscopy. Knowledge of the sensitivity, specificity and accuracy of the diagnostic procedures makes it possible to carry them out in a standardized, logical sequence. Arthroscopy allows a decidedly more accurate diagnosis than any of the other methods, but as it is an invasive procedure it should be kept until last when diagnosis of disorders of the gleno-humeral joint is required. PMID- 2203145 TI - [Sonographic diagnosis in blunt thoracic trauma]. AB - Chest sonography after blunt thoracic trauma allows the immediate institution of emergency treatment before X-ray examination. Especially in cases of hemothorax or/and hemopericardium, ultrasound is more specific and sensitive than conventional X-ray. A definite diagnosis of pneumothorax is possible when the typical sonographic findings are present: there is a strong line of reflexes along the chest wall, with complete extinction. Unilateral intensification of air stipulated repeating echoes may be a sign of mantle pneumothorax. Ruptures of the diaphragm are usually recognizable on radiographic examination only when there is massive intrathoracic splanchnectopia. They are better recognized by ultrasound examination, so that iatrogenic complications caused by thoracocentesis can be avoided. Continued ultrasound check-ups are necessary to reveal any secondary appearance of pleural fluid and to monitor the effect of pleural drains. Ultrasound is also useful for guidance when pleural aspirations are performed. In 64 patients sonography showed hemothorax in 39 cases (radiographic: 13 certain, 9 uncertain), hemopericardium in 1 case, and rupture of the diaphragm in 1 case (radiography: no pathologic findings in either of the last 2). In 2 cases rupture of the diaphragm seemed possible on ultrasound but was excluded by later (ultrasound) controls, and in 2 cases with ultrasound findings suggestive of pneumothorax subsequent X-ray examination confirmed the diagnosis of mantle pneumothorax. At follow-up, 29 pathologic findings according to radiographic examination were recognized on ultrasonography as liquid or organized pleural effusions or pulmonary infiltrates. False-negative or false-positive findings (apart from two supposed diaphragmatic injuries) were not recorded with ultrasound.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203146 TI - Psychological and psychiatric aspects of HIV infection. PMID- 2203147 TI - Effect of nasal-CPAP on patients with chronic obstructive pulmonary disease. AB - Patients with chronic obstructive pulmonary disease [COPD] breath at large lung volumes because of dynamic hyperinflation. Their end-tidal lung volumes will then be much above the equilibrium position of the respiratory system and the elastic recoil pressure would be above zero at end-tidal exhalation. This auto or intrinsic positive end-expiratory pressure [auto-PEEP] contributes to the elastic work of inspiration and the sensation of dyspnoea. The purpose of this study was to offset the auto-PEEP in patients with exacerbated chronic airflow obstruction by applying continuous positive airway pressure via the nose [nasal-CPAP]. Nine out of 14 patients experienced alleviation of dyspnoea while on nasal-CPAP [4 to 8 cmH2O]. These 9 patients had significantly more severe hyperinflation than the 5 patients who did not respond positively to nasal-CPAP. While there is a complex relationship between intrinsic and extrinsically applied PEEP in patients with COPD, the result of this study is consistent with the notion that CPAP may alleviate dyspnoea by reducing auto-PEEP, improving lung mechanics and unloading the inspiratory muscles. Nasal-CPAP may have a potential therapeutic role in exacerbations of COPD. PMID- 2203149 TI - Useful ultrasonic parameters pertaining to intra uterine fetal well being and growth retardation. AB - The true gestational age of the fetus is of great importance especially when there is an apparent discrepancy between the size of the fetus and the period of amenorrhoea. Various Ultrasonic measurements of the fetus have been used at different gestational periods to help arrive at the true gestation and to confirm or exclude intra uterine growth retardation. Recently, dynamic studies on the fetal blood flow through the umbilical artery and also the uterine vessels have provided an additional measurement of the internal milieu. These tests have been found to be extremely useful and of prognostic value even before changes occur in the CTG patterns. PMID- 2203148 TI - The Burch Colposuspension operation for stress urinary incontinence. AB - One hundred and thirteen patients with genuine stress incontinence were treated by a modified Burch Colposuspension after having failed an adequate trial with medical management. Three-quarters of patients were evaluated with pre-operative video-cystometry (video-C.M.G.) while a third underwent post-operative video cystometry. Flow rates were generally lower after surgery with 3 of the 113 patients developing post-surgery bladder instability. Previous incontinence surgery and higher parity produced statistically a greater number of failures. The overall subjective success of the operation was 80% with another 12% improved at 2 years. A 5 year long-term questionnaire follow-up did not demonstrate marked changes in these figures. The operation itself carries a 16% incidence of significant early complications, while late complications totalled 23%, the latter being primarily minor conditions. Patients left hospital after an average of 10 days. PMID- 2203150 TI - Management of systemic sclerosis--a review. AB - Establishing a correct diagnosis is the first step in the management of this condition. The ARA (American Rheumatism Association) diagnostic criteria is a useful guideline. Next, a multisystem evaluation is needed to define the extent of visceral involvement. Patient education is important to enable them to understand and participate in the management of their disease. Skin care and protection from trauma and cold and physiotherapy to retard contractures are taught. Raynaud's phenomenon may be helped by topical nitrates, ketanserin, nifedipine and vasodilatory prostaglandins. D-penicillamine may be tried for patients with generalised scleroderma of less than 3 years' duration. Colchicine may help but other drugs like N-acetylcysteine and chlorambucil have tested and found ineffective. Cyclosporin seems promising. Finally, all visceral complications should be managed accordingly. PMID- 2203151 TI - Organ transplantation: who decides? AB - The author surveys the organ transplantation procurement program and identifies problems that the successes in this new field are creating. A major problem--the growing gap between the demand for and supply of transplantable human organs--is examined, and the need for ensuring equity of access to limited numbers of organs is discussed. In addition, the various approaches to solving the problem of inequity are reviewed, and the contributions that social workers can make to decision-making processes are discussed. Social work roles at the societal, institutional, and individual case levels are proposed, and suggestions for effective role performance are noted. PMID- 2203152 TI - Adoption, infertility, and the new reproductive technologies: problems and prospects for social work and welfare policy. AB - In this article, the author examines the social and psychological issues raised by infertility and addresses problems resulting from the increasing commercialization of children through adoption practices as well as through the proliferation of new reproductive technologies. The author begins with a discussion of infertility and considers some aspects of adoption, the traditional solution to infertility. Some historical, technical, ethical, psychological, and social aspects of artificial insemination, along with newer developments of surrogacy, such as in vitro fertilization and frozen embryos, also are discussed. Recommendations are suggested for meeting the service needs of people who have problems associated with infertility. Finally, the author stresses the importance of research along with the necessity for social workers to take a leadership role in helping society both to understand the ethical issues related to and to develop enlightened public policy on infertility, adoption, and the new reproductive technologies. PMID- 2203153 TI - Circadian rhythms in general. AB - Circadian rhythms in humans are a mixture of endogenous and exogenous components that are derived from the body clock and the interaction between our environment and lifestyle. Inherently, the body clock tends to run slow (by solar time) with a period of about 25 hours. Under normal circumstances, however, zeitgebers adjust it to run with a period of exactly 24 hours. The important zeitgebers in humans appear to be a mixture of bright light and social factors. Recent evidence favors the hypothalamic suprachiasmatic nuclei as a site of the body clock in mammals, though other sites, including the pineal gland, might also play some role. Circadian rhythms not only enable us to adjust better to our rhythmic environment but also influence our responses to disease processes and drugs. Moreover, when our lifestyles are altered abruptly, our body clock is slow to adjust. The result is the symptoms associated with "jet lag" and the general malaise suffered by many nightworkers. PMID- 2203154 TI - Shiftworker performance. AB - Nightwork not only taps into the "low ebb" of certain circadian performance rhythms, it also involves sleep disruption, social and domestic disruption, and the chronic equivalent of jet lag, all of which can radically affect performance and safety. This chapter discusses performance rhythms, their relationship to the circadian system and the sleep/wake cycle, and "on-the-job" shiftworker performance. PMID- 2203155 TI - Sleep patterns of shiftworkers. AB - Work hours affect sleep because the sleep behavior of people on nonworkdays differs from that on workdays. For most workers, workday sleep is shorter than nonworkday sleep. On nonworkdays most workers sleep at night. Work schedule interacts with the effects of work hours on workday sleep. On workdays, people on the nightshift sleep the least, people on the afternoon/evening shift sleep the most, and people on the dayshift sleep less than those on the afternoon/evening shift but more than those on the nightshift. Thus, the infradian sleep strategy elected by a shiftworker is ordinarily related to the schedule worked. Despite historical preconceptions that nightshift work disturbs sleep, the primary problem appears to be a workday reduction in sleep length, which most workers do not usually compensate for by getting more sleep on their nonworkdays. Polysomnographic studies of workers on the nightshift show ultradian sleep-stage sequencing similar to that of people who have chronically reduced their usual sleep duration. This chronic reduction in sleep length is evident in data from experienced night shiftworkers, including those who most prefer to work nights. Experienced night shiftworkers also manifest decrements in performance of the sort expected of people suffering from chronic sleep deprivation. It seems reasonable to suggest that chronic sleep deprivation of night shiftworkers may often be a productivity, safety, or health hazard. Sleep disorders may be a secondary problem also facing night shiftworkers. In general, shiftworkers who do night shiftwork report difficulty falling asleep or staying asleep at rates higher than workers who do not work nights. Data suggest that this may be due to the regular practice of inappropriate infradian sleep strategies or to chronic napping habits. At this point in our study of shiftworker sleep behavior, there is as yet no clear evidence that night shiftworkers suffer from clinical sleep disorders at a higher rate than other workers. It is reasonable to suggest that occupational health professionals can make initial assessments of the sleep complaints made by night shiftworkers. Subjective measurements can be used for these assessments if care is taken to use appropriate methods. It is recommended that this data be collected by asking workers quite literal and concrete questions about the time of day they usually elect to go to sleep and get up. A sleep survey of this sort should gather main sleep period and napping times for both workdays and nonworkdays, so that the infradian sleep strategy of the worker can be identified.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2203156 TI - Health effects of sleep deprivation. AB - This report provides information supporting the conclusion that sleep deprivation produces only very small biomedical effects. It nonetheless concludes that chronic partial sleep deprivation may contribute to gastrointestinal disorders, cardiovascular disease, and other medical conditions that occur more often in shiftworkers than in permanent dayworkers. PMID- 2203157 TI - Clinical chronobiology: relevance and applications to the practice of occupational medicine. AB - In this chapter, the topic of medical chronobiology has been presented. Emphasis has been placed on issues related to clinical and occupational medicine. Results of initial studies conducted primarily by clinical pathologists indicate that the results of several commonly ordered diagnostic tests are influenced in a significant way according to the circadian time when samplings or tests are conducted. In addition, the pharmacokinetics and pharmacodynamics of medications can vary significantly according to their administration time. Indeed, the safety as well as efficacy of certain medications or dosage forms are circadian time dependent. A new thrust in the clinic is the application of chronotherapeutics to maximize the effectiveness and safety of medications. For the occupational health practitioner, the topic of medical chronobiology offers new perspectives to better address common problems experienced in clinical occupational medicine. First, the utilization of time-qualified (for circadian rhythmicity) reference values serves to differentiate with greater precision normal from unusual test findings; for example, among those arising during the pre-employment and scheduled follow-up physical examinations. Second, it provides better insight into the basis for the biological intolerance to rotating shiftwork. Too often, employee complaints of shiftwork intolerance are met with skepticism by members of the management and/or medical staff. The phenomenon of biological intolerance to rotating shiftwork is real. It has only been during the past decade that shiftwork intolerance has been demonstrated to have a chronobiologic basis. It seems that persons who possess a weak circadian time structure, that is, rather low-amplitude bioperiodicities, are more prone to develop biological intolerance to shiftwork later in life. Those endowed with a strong (high-amplitude) time structure are least prone. Thus, although persons with a weak circadian time structure might be at an advantage in tolerating rotating shiftwork schedules while young, they appear to be at a high risk of developing intolerance to it later in life. It is hypothesized that a weak circadian time structure predisposes one to desynchronization when subjected to work schedules entailing regular disruption of the activity-rest synchronizer schedule. The mechanisms underlying this biological intolerance to shiftwork require much additional investigation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2203158 TI - Shiftwork: effects on sleep and health with recommendations for medical surveillance and screening. AB - This article reviews diseases that are aggravated by shiftwork (gastrointestinal and cardiovascular disorders), the potential of shiftwork to adversely affect pregnancy, shift maladaptation syndrome, and the ability of shiftwork to exacerbate existing disorders and interfere with pharmacological treatments. It offers guidelines for pre-employment screening and medical surveillance of shiftworkers. PMID- 2203159 TI - Psychiatric aspects of shiftwork. AB - There is little rigorous evidence that shiftwork produces specific psychiatric disturbances. Substantial evidence suggests that shiftworkers are prone to increased drug and alcohol consumption, but the frequency with which this leads to actual drug abuse disorders has never been adequately defined. A preponderance of studies suggests that symptoms of a "neurotic" character are overrepresented among nightshift workers. The nature of these symptoms needs to be clarified with modern psychiatric nomenclature. It seems likely, based on certain experimental work, that nightshift work may at times exacerbate mood disorders, leading to an impression of "neurotic" disturbance. At the same time, some conditions of shiftwork might actually palliate mood disorders. Therefore, a reexamination of these issues is needed with improved research designs and more careful characterization of the nature of workers' complaints, their psychiatric histories (i.e., personal and family histories of mood disorders and other psychopathology), and possible specific effects of particular shiftwork rotation schedules. Use of bright light to alleviate mood disturbances associated with shiftwork needs extensive empirical testing. PMID- 2203160 TI - Shiftwork effects on social and family life. AB - Advantages and disadvantages of different work schedules--fixed days, fixed afternoons, fixed nights, and rotating shifts--are reviewed in terms of social satisfaction and adjustment for the worker and his or her family. The chapter also calls for new studies assessing the impact of changes in the complexion of the workforce and composition of the American family on shiftworker satisfaction. PMID- 2203161 TI - Circadian rhythm desynchronosis, jet lag, shift lag, and coping strategies. AB - Jet lag and shift lag have similar physiological consequences, but shift lag is a more complex problem. The most severe desynchronization may be experienced by airline personnel making transmeridian flights. Coping strategies for eastward and westward travelers and for shiftworkers are recommended, as are interventions involving melatonin. PMID- 2203162 TI - Shiftwork and safety in aviation. AB - For airline pilots, sleep deprivation and circadian desynchronization due to rapidly rotating shift schedules, rapid time zone changes, and unorganized sleep/wake cycles can result in severe performance decrements. Twelve case histories of accidents in which pilot scheduling might have been a factor are reviewed, and suggestions for the chronohygiene of pilot scheduling are made. PMID- 2203163 TI - Intervention factors for promoting adjustment to nightwork and shiftwork. AB - This chapter reviews a broad range of factors that, if controlled, might promote adaptation to nightwork, shiftwork, and extended workshifts. Systematic study has begun in four of the areas reported here: work schedule design, napping, bright light stimulation, and drugs. Physical activity, ambient temperature, diet, and individual behaviors have been studied only superficially. PMID- 2203164 TI - Shiftwork in developing countries: current issues and trends. AB - This chapter reviews a few studies on shiftwork in countries of Asia and South America. The developing countries need a different approach to managing shiftwork from those used in developed nations--one that concentrates more on the social consequences of shiftwork, particularly for the large proportion of female workers engaged in permanent nightwork. PMID- 2203165 TI - [Bladder hemangioma. Presentation of a case and review of the literature]. AB - The Authors report a case of hemangioma of the bladder, probable relapse of a similar neoplasia treated with endoscopic diathermy 28 years before, in a 34 year old patient. The clinical presentation, the localization, the subject's age, the therapy and the lesion's histological type recall the main features of this neoplasia. Contrary to all traditional concepts, the diagnosis was made after a biopsy, with no particular problems occurring during the examination. The localization in the bladder dome allowed a good surgical exeresis in a healthy tissue causing a further relapse to be unlikely despite the muscular invasion of the neoplasia. PMID- 2203166 TI - [Occult carcinoma in urology. Nosography and diagnosis]. AB - The term "unknown carcinoma" may be referred to any tumour that is not revealed by clinical examination or by routine diagnostic measures; the same term can indicate metastases whose source remains unknown until revealed by autopsy. The definition of the tumour histotype is mandatory for a correct choice of curative or a palliative treatment; therefore, a recognition of primary tumour should be cunningly aimed at. With regard to imaging diagnostics, some highly paramagnetic molecules for RM will shortly be available; with regard to nuclear medicine, some gamma-releasing immuno-specific markers reacting with tumour-associated antigens are also made available. Laboratory advances nowadays afford a better definition of biopsy samples, namely monoclonal antibodies versus cytospecific antigens and/or tumour-associated antigens; immuno-histochemical markers, such as anti-AFP and anti-HCG monoclonals, that detect the testicular source (germinal tumours) of a highly undifferentiated retroperitoneal mass; etc. It seems therefore possible the foresee a reduction in the incidence of "unknown" carcinomas. PMID- 2203167 TI - [Suspension of the bladder neck for urinary stress incontinence under local anesthesia]. AB - Bladder neck suspension under local anesthesia is a new technique for the treatment of stress incontinence in females which can be done under private clinic conditions. The procedure is a modification of Stamey-Pereyra operation. It has already been applied in 34 patients with a success rate of 80% with low morbidity. A higher success rate was achieved in patients who had no gynaecological or surgical operations previously. The purpose of the technique that we used on these patients is to restore anatomic position without causing urethral obstruction. PMID- 2203168 TI - [Paraneoplastic syndromes associated with bladder carcinoma. Apropos of 2 cases of hypercalcemia]. AB - Apart from presenting a specific symptomatology, cancer of the bladder in some rare cases may present with a set of symptoms that at first sight seem unrelated to the tumour and that constitute the paraneoplastic syndromes. The importance of these paraneoplastic symptoms is represented by the fact that they may constitute the first sign of malignity, or may be the expression of a recurrence. Two rare cases of paraneoplastic hypercalcemia are reported, the literature is reviewed and the aspects of this rare pathology are analysed. PMID- 2203169 TI - [Ultrasonic diagnosis of polypoid formations of the gallbladder]. AB - Altogether 4000 patients were examined using an ultrasonograph Toshiba SAL 38AS working in the real time mode. 1.08% of the patients were diagnosed to have small polypoid formations of the gallbladder which, in many cases, could not be recognized at oral cholecystography. Routine repeated sonography of the gallbladder demonstrated that in 94.9% of cases, small polypoid formations did not increase in size for 12 to 18 months. Four patients subjected to cholecystectomy manifested polypous cholesterosis of the gallbladder. PMID- 2203170 TI - [Immunologic mechanisms of the development of nonspecific aortoarteritis]. AB - It has been shown that patients with nonspecific aortoarteritis undergoing acute and subacute stages of the process demonstrate sensitization to collagen, types I and III. The activity of inflammation was discovered to affect the disease progression and involvement of new arterial areas. Marked suppression of leukocyte migration in response to collagen, types I and III, in patients with nonspecific aortoarteritis points to a high probability of further disease progression. PMID- 2203171 TI - [Echo contrast study of myocardial perfusion]. PMID- 2203172 TI - [Chronobiological aspects of studying the cardiovascular system]. PMID- 2203173 TI - [Diseases of the cardiovascular system and the function of the endocrine glands in veterans of Soviet Antarctic expeditions]. AB - The authors examined 58 men who had repeatedly participated in the Antarctic expeditions. In addition to a profound study of the cardiovascular system, the insulin tolerance test (0.1 U/kg simple insulin injected by intravenous drip for 90 minutes) was made, permitting the degree of tissue insulin resistance to be quantitatively estimated with measurements of the content of cyclic nucleotides in blood leukocytes and of immunoreactive insulin, C-peptide and counterinsular hormones in the blood before and after the functional test. It was established that with the increase of the number of Antarctic winterings tissue insulin resistance naturally grows regardless of the age of the examinees, manifesting itself in an increase of basal insulinemia, the content of cyclic adenosine monophosphate in blood leukocytes, appreciable increment of insulinemia after infusion of exogenous insulin. Analogous changes were detected in polar researchers suffering from coronary disease, essential hypertension irrespective of the number of winterings. It is concluded that the rise of tissue insulin resistance occurring under the influence of multiple exposures to natural and social factors of high latitudes is a predisposing factor of the formation of cardiovascular pathology. PMID- 2203174 TI - [Postpericardiotomy syndrome after surgery of the heart]. PMID- 2203175 TI - [Serum neopterin in dilated cardiomyopathy]. AB - RIA was used to measure the level of neopterine and beta 2-microglobulin in the sera of 43 patients with a verified diagnosis of dilated cardiomyopathy (DCMP). In DCMP patients, the mean level of neopterine was 11.25 +/- 1.05 nM/l and was significantly higher than in donors (5.6 +/- 0.5 nM/l). The concentration of neopterine exceeding 9 nM/l was discovered in 55% of DCMP patients. The rise of neopterine concentration was particularly marked in patients with inflammatory reaction in the myocardium according to endomyocardial biopsy. In that patients' group, the mean level of neopterine was 12.9 +/- 2.02 nM/l while the rise of its concentration over 9 nM/l was recorded in 9 (81%) of 11 patients examined. The correlation was established between the rise of the concentration of neopterine and beta 2-microglobulin. In patients with the concentration of neopterine over 9 nM/l, the mean level of beta 2-microglobulin constituted 3.33 +/- 0.32 mg/l and in patients with the normal concentration of neopterine, it amounted to 1.91 +/- 0.18 mg/l. The growth of the concentration of beta 2-microglobulin in the groups of patients under comparison was seen in 79 and 14% of cases, respectively. It is concluded that neopterine measurements are advisable in the laboratory diagnosis of myocarditis in DCMP patients. Potential mechanisms of the rise of neopterine formation are discussed from the standpoint of hyperinterferonemia. PMID- 2203176 TI - New reproductive technologies in the treatment of human infertility and genetic disease. AB - In this paper I will discuss three areas in which advances in human reproductive technology could occur, their uses and abuses, and their effects on society. First is the potential to drastically increase the success rate and availability of in vitro fertilization and embryo freezing. Second is the ability to perform biopsies on embryos prior to the onset of pregnancy. Finally, I will consider the adding or altering of genes in embryos, commonly referred to as "genetic engineering". As new reproductive technologies pass from experimental models into the potential for medical utilization, I believe that it will be important for lawmakers everywhere to avoid the impulse to outlaw procedures that a society believes to be 'unnatural' at a first glance. Rather, I would hope that they can respond thoughtfully with legislation that serves two purposes--to protect the rights of couples to overcome infertility or to reduce the risk of genetic disease in their children-to-be, and more importantly, to protect children-to-be from the abuses that could result from some of the practices that I will discuss. PMID- 2203177 TI - Integrating medical ethics with normative theory: patient advocacy and social responsibility. AB - It is often assumed that the chief responsibility medical professionals bear is patient care and advocacy. The meeting of other duties, such as ensuring a more just distribution of medical resources and promoting the public good, is not considered a legitimate basis for curtailing or slackening beneficial patient services. It is argued that this assumption is often made without sufficient attention to foundational principles of professional ethics; that once core principles are laid bare this assumption is revealed as largely unwarranted; and, finally, that these observations at the level of moral theory should be reflected, in various ways, in medical practice. Specifically, this essay clarifies a tension that exists between different kinds of moral principles and explores the possibility of dissipating that tension by shoring up foundational principles. The paper begins by setting out three alternative models of how best to balance patient advocacy responsibilities with broader social responsibilities. It then turns to critically assess these models and argue that one has several advantages over the others. PMID- 2203178 TI - Social context and historical emergence: the underlying dimension of medical ethics. AB - I argue that work in medical ethics which attempts to humanize medicine without examining hidden assumptions (about medicine's ontology, explanations, goals, relationships) has the dehumanizing effect of legitimating practices which treat persons as abstractions. After illustrating the need to reexamine the field of medical ethics and the doctor-patient relationship in particular, I use Foucault's work to provide a social, historical framework for discussion. This background begins to demonstrate that doctor-patient relationships cannot be made satisfactory by new hospital policies or interpersonal skills, but have deep rooted problems due to medicine's place in social history. Real progress requires social or structural change. PMID- 2203180 TI - Physiology and treatment of cough. PMID- 2203179 TI - The ethical assessment of innovative therapies: liver transplantation using living donors. AB - Liver transplantation is the treatment of choice for many forms of liver disease. Unfortunately, the scarcity of cadaveric donor livers limits the availability of this technique. To improve the availability of liver transplantation, surgeons have developed the capability of removing a portion of liver from a live donor and transplanting it into a recipient. A few liver transplants using living donors have been performed worldwide. Our purpose was to analyze the ethics of liver transplants using living donors and to propose guidelines for the procedure before it was introduced in the United States. We used a process of "research ethics consultation" that involves a collaboration between clinical investigators and clinical ethicists. We concluded that it was ethically appropriate to perform liver transplantation using living donors in a small series of patients on a trial basis, and we published our ethical guidelines in a medical journal before the procedure was introduced. We recommend this prospective, public approach for the introduction of other innovative therapies in medicine and surgery. PMID- 2203182 TI - 1990 Frank R. Blood Award. PMID- 2203181 TI - Controlled trial of natamycin in the treatment of allergic bronchopulmonary aspergillosis. AB - Allergic bronchopulmonary aspergillosis often requires treatment with oral corticosteroids to control the host response to Aspergillus fumigatus. In a double blind study 25 patients with allergic bronchopulmonary aspergillosis taking maintenance oral corticosteroids were randomly allocated to receive 5 mg natamycin or placebo by nebuliser twice daily for one year. The primary aim of the study was to assess the steroid sparing potential of natamycin. Standardised reductions in corticosteroid dosage were therefore undertaken every five weeks, unless clinically contraindicated. Five patients were withdrawn in the first four months: two (1 natamycin, 1 placebo) died, two (1 natamycin, 1 placebo) had suspected drug reactions, and one (natamycin) was non-compliant. The pretreatment characteristics of the 20 patients (10 in each group) who completed the study were similar, 17 (9 natamycin, 8 placebo) having evidence of recent disease activity. At the end of the study prednisolone dose had been reduced by a similar amount in each group (median natamycin 2.25 mg, placebo 2.5 mg). Evidence of disease activity during the study year (transient shadowing on the chest radiograph, blood eosinophilia, or increases in antibodies to A fumigatus, or any combination of these) was observed in similar numbers of patients in each group (5 natamycin, 7 placebo). There was no evidence that natamycin conferred benefit on these patients with allergic bronchopulmonary aspergillosis. PMID- 2203183 TI - 1990 Education Award. PMID- 2203184 TI - 1990 Achievement Award. PMID- 2203186 TI - 1990 Merit Award. PMID- 2203185 TI - 1990 Arnold J. Lehman Award. PMID- 2203187 TI - 1990 Burroughs Welcome Toxicology Scholar Award. PMID- 2203188 TI - An immunofluorescence study of T and B lymphocytes in ozone-induced pulmonary lesions in the mouse. AB - Ozone is a photochemical oxidant which reacts with a variety of biological molecules. In experimental animals the toxicity of ozone results from damage to cells in the lung and is associated with the process of reactive repair and an influx of inflammatory cells. In this work we used an indirect immunofluorescence technique to study the effect of ozone on T and B lymphocytes with special reference to their presence in ozone-induced pulmonary lesions. BALB/c mice were exposed to ozone at a concentration of 0.7 ppm for 20 hr per day, 7 days per week, for 4 or 14 days. Control mice were housed in comparable chambers lacking ozone. Frozen sections of lung were prepared and stained for the surface markers Thy-1.2 (T lymphocyte) and sIgM (B lymphocyte). These experiments showed that T lymphocytes infiltrate the lung lesions during ozone inhalation, and increase their presence as ozone exposure continues. They were present in the centroacinar region and tended to occur in clusters within the ozone-induced lesions. In contrast, the infiltration of B lymphocytes was virtually nonexistent with few or no sIgM positive cells present in the lesions after either 4 or 14 days of exposure to ozone. These results show that T lymphocytes occur within the sites of ozone-induced damage and support that this cell type plays a role in the reactive host response to ozone inhalation. PMID- 2203189 TI - More selective ligands at eicosanoid receptor subtypes improve prospects in inflammatory and cardiovascular research. PMID- 2203190 TI - Understanding of the molecular basis of drug resistance in cancer reveals new targets for chemotherapy. PMID- 2203191 TI - Nimodipine and the recovery of memory. PMID- 2203192 TI - The role of membrane biophysical properties in the regulation of protein kinase C activity. AB - Under physiological conditions, protein kinase C is active when bound to membranes. Like most membrane-bound enzymes, its activity is dependent on the nature of its lipid environment. In this article, Richard Epand and David Lester describe the relationship between the ability of specific membrane-active agents to alter the biophysical properties of the lipid environment and their potential to modulate protein kinase C activity. They argue that this can lead to a greater understanding of the mechanism of inhibition and activation of protein kinase C through modulation of the bulk biophysical properties of the membrane, and may provide a new approach to the development of a more specific set of inhibitors. PMID- 2203193 TI - Flavin-containing monooxygenases: enzymes adapted for multisubstrate specificity. AB - Unlike all other oxidases, microsomal flavin-containing monooxygenases (FMO) discriminate between essential and foreign compounds by excluding the former rather than selectively binding the latter. As Daniel Ziegler describes here, xenobiotics that readily cross cell membranes can enter the catalytic cavity, whereas charged groups on essential metabolites that prevent their passive diffusion out of the cell also block their access to FMO. FMO appears to be ideally adapted to catalyse the detoxification of structurally diverse soft nucleophiles (e.g. alkaloids with basic side-chains and organic sulfur xenobiotics) so abundant in food derived from plants. PMID- 2203194 TI - Sensory neuron-specific actions of capsaicin: mechanisms and applications. AB - Capsaicin acts specifically on a subset of primary afferent sensory neurons to open cation-selective ion channels, probably by interacting directly with a membrane receptor-ion channel complex. Another plant product--resiniferatoxin- has structural similarities to capsaicin and opens the same channels, but is up to 10,000 times as potent. Capsaicin-sensitive neurons are involved in nociception, are responsible for the neurogenic component of the inflammatory response and may also have efferent actions in the peripheral target tissues. In addition to its excitatory actions, capsaicin can have subsequent antinociceptive and anti-inflammatory effects. For these reasons Stuart Bevan and Janos Szolcsanyi argue that drugs based on capsaicin and resiniferatoxin may have important clinical uses. PMID- 2203195 TI - On the origin of sonoluminescence and sonochemistry. AB - Recent experimental results on the origins of sonoluminescence and sonochemistry are reviewed and the conclusion reached that most observed effects originate from thermal processes associated with a localized hot-spot created by acoustic cavitation. Sonoluminescence is definitively due to chemiluminescence from species produced thermally during cavitational collapse and is not attributable to electric microdischarge. Homogenous sonochemistry follows the behaviour expected for high temperature thermal reactions. Ultrasonic irradiation of liquids containing solid powders dramatically increases their chemical reactivity and improves chemical yields for a wide range of synthetically useful heterogenous reactions. Shock waves generated from the cavitational hot-spot cause high velocity interparticle collisions in such slurries. Brittle solids are shock fragmented, which increases surface area. This increase in reactive surface provides for substantial increases in chemical reactivity. For malleable metal powders, these collisions are sufficiently violent to remove surface oxide coatings and to induce local melting at the site of impact for most metals. PMID- 2203196 TI - Sonochemistry of volatile and non-volatile solutes in aqueous solutions: e.p.r. and spin trapping studies. AB - Recent spin trapping studies of the free radical intermediates generated by the sonolysis of aqueous solutions are reviewed. Studies of rare gas saturated solutions of volatile solutes (e.g., methanol and ethanol) and of non-volatile solutes (acetate, amino acids, sugars, pyrimidines, nucleotides and surfactants) are consistent with the theory of three reaction zones in aqueous sonochemistry. The very high temperatures and pressures induced by acoustic cavitation in collapsing gas bubbles in aqueous solutions lead to the thermal dissociation of water vapour into hydrogen atoms and hydroxyl radicals. Reactions take place in the gas phase (pyrolysis reactions), in the region of the gas-liquid interface, and in the bulk of the solution at ambient temperature (similar to radiation chemistry reactions). By use of the rare gases with different thermal conductivities, the contributions of individual reaction steps with widely different energies of activation can be evaluated. PMID- 2203197 TI - Development and testing of second generation extracorporeal shock-wave lithotriptor. AB - The Northgate SD-3 extracorporeal shock-wave lithotriptor is a second generation device that utilizes an ultrasound-guided computer-assisted system for calculus localization. Focused electrohydraulic shock waves are generated in a movable membrane-covered ellipsoidal reflector. Pressure wave characteristics and energy output of the SD-3 and the Dornier HM-3 were tested and found to be comparable. The ultrasound unit was capable of identifying radiolucent calculi as well as calculus fragments 2-3 mm in size. The computer-assisted aiming system was found to be accurate to within 1 mm. The overall successful calculus fragmentation rate using an animal model was 80 percent with an 87.5 percent rate following machine modifications resulting in increased energy output. PMID- 2203198 TI - Transperineal seed-implantation guided by biplanar transrectal ultrasound. AB - A new method for precise transperineal placement of therapeutic sources in prostatic cancer is described. The method is a modification of the technique described in 1983 by Holm and coworkers. Insertion of needles is monitored by transverse as well as longitudinal transrectal ultrasound. PMID- 2203199 TI - Accuracy of ultrasound in diagnosis of rupture after blunt testicular trauma. AB - In 6 patients who underwent ultrasound scanning and operation after blunt testicular trauma, the scan suggested the correct diagnosis in only 2 patients. There was one false-positive and three false-negative diagnoses of rupture. Absence of firm diagnostic criteria for rupture and high error rates with various criteria now in use make reliance on ultrasound in the diagnosis of testicular rupture inappropriate at this time. PMID- 2203200 TI - Branched, struvite calculus and clear cell carcinoma in same kidney. Rare condition with significant implications for management. AB - The concomitant existence of a branched (partial staghorn) calculus and clear cell carcinoma (hypernephroma) in the same kidney is rare. Herein, we report the eighth such case in the world literature, and to our knowledge, the first patient with a parenchymal tumor identified preoperatively. In all of the previous 7 cases, the calculus was managed with open renal exploration, and only at the time of surgery was the incidental renal cell carcinoma identified; the surgical procedure was modified accordingly. With open surgery no longer the cornerstone of therapy for renal calculi, it is imperative that the kidney be evaluated in a meticulous and compulsive manner prior to extracorporeal shock wave lithotripsy (ESWL) or percutaneous nephrolithotomy (PNL). The finding of a coexisting renal cell carcinoma will radically alter the patient's treatment. PMID- 2203201 TI - Robert S. Hotchkiss, M.D.--remembered. PMID- 2203202 TI - Small electric currents affecting farm animals and man: a review with special reference to stray voltage. I. Electric properties of the body and the problem of stray voltage. AB - The literature on the electrical properties of the body and sensitivity to steady electric current in humans and farm animals is reviewed and the problem of stray voltage is examined. Stray voltage poses a problem to animal health and protection in cattle and pigs and possibly also in other animals. Dairy cattle can perceive alternating currents exceeding 1 mA between the mouth and all four hooves. Behavioural effects in cows usually occur above 3 mA. In practice, the major influence on dairy cows appears to be behavioural. In experimental research on sensitivity to electric current, the effects studied should be related primarily to the actual current densities or electric fields in the affected tissues rather than to the total voltages applied. Under normal conditions, herdsmen are less likely to be affected by stray voltage than their animals. PMID- 2203203 TI - Small electric currents affecting farm animals and man: a review with special reference to stray voltage. II. Physiological effects and the concept of stress. AB - The literature on the influence of small, steady electric currents on animal health, especially cardiovascular and endocrinological functions and milk let down, and the effects on milk production is reviewed, with special reference to the problem of stray voltage. Direct physiological effects in cows may occur above 4 mA. How the long-term effects may contrast with the acute effects is not known. Habituation may occur. The altered behaviour and physiological changes due to exposure to stray voltage may be termed a stress response. The type of stress most likely to be encountered is chronic. Whether or not stress occurs depends on the timing and context of exposure and on individual cognition. Hence stray voltage may threaten farm animal health and production wherever modern animal housing is applied. PMID- 2203204 TI - [Stress-strain approach--a principle for ergonomic studies]. AB - In the terminology of occupational hygiene and the WAO no distinction has been made to date between "load" and "strain". Occupational medicine and ergonomics by contrast, in addition to differentiating between the terms, have been developing the "load-strain approach" since about 1970. After outlining the historical development of the terms and explaining them, the approach is derived and presented in a simple and extended form. Starting from demands made by the WAO, the significance of the approach for the planning and execution of ergonomic investigations is explained. In the approach differentiation between the "description", "assessment" and "judgement" of working conditions is recommended. Possible approaches and criteria for forming a judgment are presented and discussed, with special attention being paid to models for the operationalization of strain. A concept for pragmatic judgment is presented after discussion about the necessity, frequently encountered in practice, of balancing the demands of providing scientific proof and of arriving at decisions relevant to practical problems. PMID- 2203206 TI - [The urban hospital system in Leipzig at the turn of the century]. AB - The development of the hospital in Germany up to 1914 had been realized by the establishment of medicine of natural science, combined with a sensible progress of diagnostics and therapy. Thus the character of the stationary care changed in Leipzig by 1900. This process had been supported by an organization separating care of patients from those of poor subjects. A reconstruction and improvement of the municipal hospitals could be gained by the erection of the Nursing Home for Mental Cases in Leipzig-Dosen (1901), of the Leipzig Tuberculous Sanatorium Sorg at Adorf (1906) and of the Municipal Hospital St. Georg (1911-1913). PMID- 2203205 TI - [Current state of knowledge regarding prenatal effects of benzene]. AB - The present knowledge concerning the possible prenatal effect of benzene and/or its metabolites is presented. Animal experimental results and epidemiological studies proved to be completely insufficient. The physical, chemical and biochemical properties of this ubiquitously occurring solvent, especially the specific effects on the erythropoetic system including the damage of the cyto skeleton of the cells, require an enhanced attention in the cases of exposure of female workers in child bearing age and of pregnant women to benzene, even in cases of surely observing the maximum allowable concentration at work places. PMID- 2203207 TI - [Work in very hot, dry climates: evaluation of stress and procedures for reducing strain on the human body]. AB - Even in temperate zones of the earth such as Middle Europe quite a number of men have to work in very hot dry climates, particularly in salt mines. Problems of evaluation stress under these condition are discussed. Climatic chamber experiments at ambient temperatures mainly between 45 and 65 degrees C were performed in order to find out various possibilities to reduce heat strain. New methods are discussed for reducing extremely elevated body core temperatures. PMID- 2203208 TI - [Thrombolytic therapy in acute myocardial infarct. 2. Clinical studies with thrombolytic therapy]. AB - The highly dosed short-term therapy of thrombolysis with intravenous streptokinase at the beginning of therapy less than or equal to 6 angina pectoris time has with a high probability as a consequence the early recanalisation of a coronary thrombosis. A reduction of the lethality is significant, however, furthermore also patients with longer angina pectoris time have advantages. The combination of the intravenous streptokinase therapy with the immediate medication of acetyl salicylic acid (ASA) is a decisive factor for the decrease of the reocclusion and the reinfarction rate, respectively, and thus for the limitation of the lethality. The early intracoronary streptokinase therapy is no more indicated today. In comparison to the intravenous streptokinase the early recanalisation rate is higher in t-PA and APSAC. However, at present the results are identical at dismission from hospital. Studies in the nineties must make evident the advantages of the various substances only in the direct comparison (Sk, t-PA, APSAC). PMID- 2203209 TI - [Use of computer-assisted Doppler sonography and rheography in acral vascular diagnosis in progressive systemic sclerosis]. AB - For the quantitative characterization of the blood flow of patients with progressive systemic sclerosis a combined computer-assisted Doppler sonographic as well as rheographic measuring place was established. An aimed examination of the peripheral situation of the blood supply was performed in 15 patients with progressive systemic sclerosis in comparison to a control group of patients with healthy vessels. The demonstration of the corresponding parameters of time and form of the curves resulted in significant differences for the two examination groups, particularly of the pulsation index (PI) and the index of the peripheral resistance (PWI) in the Doppler flow curves as well as for the maximum increase (A) and the peak time (GZ) in the rheogrammes. The computer-assisted functional diagnostic investigation methods in the peripheral vascular region offer themselves for the objectivation and the assessment of the course of the participation of the vessels in the collagenoses. PMID- 2203210 TI - [New knowledge of diet therapy of type 2 (non-insulin-dependent) diabetes]. AB - The composition of the diet of the type II-diabetics should correspond to the principles of a lactovegetarian diet: relatively many carbohydrates, vegetables, fruits and little fat, in particular little animal fats. By such a pathogenetically orientated nutrition one is at the earliest able to treat successfully preventively and therapeutically the development of the arteriosclerosis which is connected with the type 2 diabetes and with metabolic syndrome. Thereby the weight reduction is of course integrated into such a dietary prescription. The number of meals a day should not routine-like be established to 5 to 6, and only in a bad metabolic condition the subdivision into many smaller meals is necessary. In the calculation of the food type 2 diabetics with overweight stabilised on diet alone should estimate the energy of food and reduce it. At this stage the calculation of carbohydrates is not necessary. Only when a blood sugar decreasing therapy is added (insulin and perhaps sulfonylureas) we have additionally to begin the calculation of carbohydrates. In order to obtain a useful compliance unnecessary reglementations must be removed so that only there where necessary a strict discipline is observed. PMID- 2203211 TI - Relevance of in vitro studies for in vivo aging. AB - Cell cultures have allowed some fundamental mechanisms of cellular biology relevant to the aging process to be studied. The deregulation of events such as cell migration, response to growth stimuli, and inductive interactions between different cell systems have been analyzed and some of the underlying molecular mechanisms were identified. A genome reorganization taking place in the hierarchical structures of DNA during cellular aging could be ascertained. The remodeling occurring in organs, tissues, and cells during aging can be now seen as the result of the structural reorganization observed at the molecular level that progresses continuously from fertilization of the egg to the extinction of the organism. This remodeling occurs in such a way as to decrease the capacity for subsequent change, approaching a condition of equilibrium; aging can be seen as the tendency to reach this limit. PMID- 2203213 TI - Action and interaction of respiratory muscles in dogs. AB - How the respiratory muscles, the so-called "vital pump", works is relevant to medicine and nevertheless, poorly understood. The present studies attempt to obtain a better insight in the action and interaction of respiratory muscles by measuring the mechanical outcome of individual respiratory muscle contraction with two different techniques in anesthetized dogs. First, we measured the changes in length undergone by respiratory muscles using sonomicrometry. We observed that the costal and crural parts of the diaphragm frequently behaved differently, supporting the concept that these two parts behave as two different muscles. Moreover, crural diaphragmatic length appeared to be linked to abdominal dimensions, the classical used estimate of diaphragmatic length, whereas costal diaphragmatic length was not. The parasternal or the interchondral parts of the internal intercostals invariably shortened with inspiration supporting their role as inspiratory agonists. By way of contrast, the respiratory length changes in the external and interosseus internal intercostal were variable and not consistently in different directions for the two layers. The changes in length, during rotation of the trunk were consistent, larger and systematically in opposite directions for these two layers, suggesting that these muscles predominantly function as rotators of the trunk or at least that a role in rotation of the trunk explains better the need for two layers of intercostal muscles with different fiber orientation than a respiratory role. Second, we measured changes in intramuscular pressure in the costal and crural parts of the diaphragm, and in the parasternal intercostals, using mini-transducers. In the diaphragm intramuscular pressure appeared to be a complex variable determined by the tension developed by the muscle as well as the pleural and abdominal pressures applied to the muscle. As a consequence, intramuscular pressure often decreased during contraction, suggesting that in contrast to other muscles, diaphragmatic contraction may enhance diaphragmatic blood flow. Conversely, in the parasternal intercostals, intramuscular pressure invariably increased during contraction, and a linear relationship between intramuscular pressure and contractile force was present. The forces developed by these muscles during quiet breathing and other respiratory maneuvers were found to be significant, supporting the important inspiratory role of the parasternal intercostals. Intramuscular pressure thus appeared to be a perfect estimate of the force developed by these muscles. Finally, we examined the changes in respiratory muscle interaction with hyperinflation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2203212 TI - [The problem of evaluating so-called aging parameters exemplified by insulin secretion]. AB - The mean aspects of insulin secretion were studied in healthy humans of 27-59 years of age by means of glucagon application and determination of C-peptide blood concentration. The results lead to the assumption that the basic insulin secretion correlates proportionally to body weight or body mass index (BMI) at the expense of the pancreas resources of this hormone. Further, aging seems to decrease the sensitivity of the beta cells' reaction to stimuli. Finally, the fact that excess weight and/or the preponderance of fat mass are usually age dependent manifestations, may lead to the conclusion that the rise of the basic insulin secretion with decrease of the pancreas resource and a progressive loss of reaction capacity of beta cells are physiological consequences of aging. PMID- 2203214 TI - [The value of physical therapy in genuine female stress incontinence]. AB - In a prospective randomized study the efficiacy of physical therapy in female stress incontinence could be verified. The greatest success rate was achieved by medical gymnastics, whereas the perineal electrical stimulation should be used as supporting measure like a biofeedback mechanism because of its low effective intensity. Despite of the good therapeutic success (51.5%) with lasting effects no objective criteria to the use of physical therapy in female stress incontinence were found. PMID- 2203215 TI - [The effect of dipyridamole on the results of allogenic kidney transplantation]. AB - In a prospective randomized trial the anti-thrombotic effect of dipyridamole was studied in 64 patients after cadaveric kidney allotransplantation. The frequency of early graft function was significantly higher in the control group, whereas the incidence of arterial and venous thromboses were not different. One-year graft survival could not be improved by dipyridamole. Therefore, dipyridamole should not be recommended in cadaveric kidney allotransplantation. PMID- 2203216 TI - Risk factor variability and coronary heart disease. AB - Present attempts to identify genes contributing to coronary heart disease (CHD) risk focus on "candidate genes". With respect to CHD this could be any gene whose protein product is directly or indirectly involved in atherogenesis, thrombogenesis or thrombolysis/fibrinolysis. Genes that exhibit associations with absolute risk factor levels may be referred to as "level genes" to distinguish them from "variability genes", which are genes involved in establishing the framework within which environmental influences may cause risk factor variation. In a series of persons recruited from the Norwegian Twin Panel, confirmatory evidence for level gene effect with respect to apolipoprotein B (apoB) concentration was found with an XbaI polymorphism in DNA at the apoB locus corresponding to residue 2,488 in the mature protein. Evidence for variability gene effect with respect to apoB as well as body mass index emerged with DNA variants in the 3' part of the apoB gene. Level gene effect with respect to apolipoprotein A-I (apoA-I) and high density lipoprotein (HDL) cholesterol as well apparent variability gene effect with respect to total and LDL cholesterol were detected with a DNA polymorphism at the cholesteryl ester transfer protein (CETP) locus. The first example of interaction between normal genes in determining risk factor level was uncovered in analysis of the apolipoprotein E (apoE) polymorphism and a restriction fragment length polymorphism (RFLP) at the low density lipoprotein receptor (LDLR) locus. An LDLR gene identified by presence of a PvuII restriction site eliminated completely the well known effect of the apoE4 allele on cholesterol level. Finally, in families where high Lp(a) lipoprotein level (a well established risk factor for CHD) segregated as a Mendelian trait, very close linkage with an RFLP at the plasminogen locus was established and DNA variation at the LPA locus reflecting varying numbers of a structure homologous to the "kringle IV" region of plasminogen was uncovered. PMID- 2203217 TI - Blood coagulation factor XIII contributes to the development of traction retinal detachment. AB - The blood coagulation factor XIII catalyzes the crosslinking of fibrin monomers at the end of the coagulation cascade. Additional functions are the enzymatic coupling of fibrinectin to itself, fibrin, and collagen. We located the two subunits of factor XIII in 20 surgically obtained periretinal membranes, using double label immunofluorescence microscopy. Both subunits of factor XIII could be detected in all specimens. The positive staining in all specimens examined prompted us to determine the source of factor XIII. The abundant fibroblastic cells did not contain factor XIII. Macrophages, half of which stained for the alpha-subunit of factor XIII could not account for the presence of factor XIII because these cells were not present in all specimens, and did not stain for the beta-subunit. Factor XIII is probably derived from the exudation of plasma and platelets through disrupted blood-ocular barriers. This is confirmed by the detection of both subunits in vitreous aspirates from patients with proliferative intraocular disorders (n = 15) by Western blotting. PMID- 2203219 TI - Ocular cicatricial pemphigoid and oesophageal carcinoma. AB - A 65-year-old man developed ocular cicatricial pemphigoid. He was treated with topical and systemic immunosuppressive agents. Three months later, he was found to have metastatic oesophageal carcinoma. To our knowledge, the association of ocular cicatricial pemphigoid and oesphageal carcinoma has not previously been described. PMID- 2203218 TI - Twelve-hour IOP control obtained by a single dose of timolol/pilocarpine combination eye drops. AB - The 12 h IOP control achieved by a single application of a newly developed ophthalmic solution containing 0.5% timolol and 2% resp. 4% pilocarpine was compared with that obtained by 1 dose of timolol 0.5% alone in 33 patients with manifest open angle glaucoma or ocular hypertension. The combined solutions gave a significantly better 12 h IOP control, evidenced by both a reduced mean diurnal IOP and a decreased frequency of larger pressure peaks. PMID- 2203220 TI - [Cranio-facial resections]. AB - Four basic steps should be considered in craniofacial tumor surgery: dismantling and re-assembling of preservable bone structures to reach the tumor; en bloc resection of the "box" in malignancies (i.e., the unaffected boundaries surrounding and including the tumor), internal rigid fixation and, reconstruction by using whenever possible regional structures. In benign tumors and so-called pseudotumors, the treatment is total removal and immediate reconstruction of all structures, including the bone. The primary goal of craniofacial surgery for malignancies is to create an entrance to the box that is to be resected. This necessitates the dismantling and reassembly of some uninvolved skeletal structures. Among these are the nose, the maxilla, the nose and maxilla en bloc, the nose and the maxilla bilaterally to the mandible. The introduction of internal rigid fixation by using plates and screws has facilitated the realignment of the pedicled bone fragments in a correct position. After cranial base resection, the communication between neuro- and splanchno-cranium must be closed with viable flaps. Many techniques have been described. The horizontal forehead flap is certainly effective but results in a significant secondary defect. Where there is an orbital resection en bloc with the cranial base, the temporalis muscle flap is effective in providing vascularized coverage and simultaneously obliterating the orbital cavity. The galeal frontal flap is versatile and easy to use. It has been used to cover anterior and lateral defects with good results. The orbit is another area that requires immediate reconstruction so that there is no resulting external defect. The temporalis muscle flap, with or without a skin island, can be used to repair it. Distant flaps can likewise be used. If the resection includes the maxilla, reconstruction of the defect can be performed immediately, or it can be delayed. The authors prefer to use the temporalis muscle flap if it has not already been used. On the basis of 10 years of experience in craniofacial surgery the following conclusions can be drawn: 1. Craniofacial surgery is not a single concept. Therefore, the surgeon who deals with facial tumors involving the cranial base must have expertise in the entire field. Oncology must be part of his basic biological education. 2. Complications functional and aesthetic consequences are minimal if some basic principles are applied, both in the resection and the primary reconstructive phase. 3. In the past few years, surgical techniques have been modified and improved considerably, resulting in an operation that combines an excellent approach, oncological resection, low postoperative morbidity, good aesthetic results and improved prognosis. PMID- 2203221 TI - [Longitudinal comparison of methods of auditory evoked potentials in defined multiple sclerosis]. AB - The object of the present paper was to evaluate the diagnostic accuracy of ABR using ipsilateral masking in patients suffering from multiple sclerosis. Fourteen patients were examined. Each patient with normal audiogram underwent two ABR recording sessions during a follow-up period of thirty months. The ABRs were recorded under two experimental conditions applying standard testing procedures and ipsilateral masking, respectively. In 5 patients magnetic resonance imaging was also available. The findings were compared with a control group, composed of 20 normal subjects. Standard ABR testing gave evidence of a pathological value in 50% of the cases while the ABRs proved to be altered in 64% under ipsilateral masking. The outcomes were less favourable than those obtained with somatosensory or visually evoked potentials. The conclusions drawn confirm the importance of ABR in the follow-up of multiple sclerosis. On the other hand, ipsilateral masking does not appear to provide any significant advantages due to poor amelioration of sensitivity and doubtful specificity of the observed alterations. PMID- 2203222 TI - [General aspects of secondary prevention and possible interventions applicable to squamous carcinoma of the upper respiratory-digestive tract]. AB - The authors report some aspects of secondary prevention, including screening programs. General standards for screening programs are first analyzed; standards including a) definition of the problem and its social importance; b) tumor natural history; c) diagnostic test characteristics; d) therapeutic possibilities; e) evaluation of results. The problem of selective screenings are then discussed as they attempt to reduce costs and maximize benefits. PMID- 2203223 TI - [Biological aspects and perspectives applicable to the chemoprevention of cancer of the upper respiratory-digestive tract]. AB - After defining chemoprevention a description is given of the phases of differentiation in normal epithelial cells and the features of proliferation in neoplasias developing in this epithelium. The latest studies on carcinogenesis indicate various types of prevention with which one can alter this transformation process. Epidemiological studies have shown that subjects with low serum levels of Vit-A or Beta carotenoids are at high risk of developing epithelial cancer. Three main categories of agents inducing cell transformation are described: a) physiological induction agents; b) non physiological induction agents; c) cytotoxic drugs. In regard to clinical use, some studies have focussed on the importance of Vit-A in chemoprevention of risk conditions (pre-cancerous lesions) and in prevention of cancer recurrence. The authors point out the increasing interest in the use of retinoids in the chemoprevention of head and neck cancer and report some personal clinical experience. PMID- 2203224 TI - [Epidemiology and natural history of cancer of the upper respiratory-digestive tract]. AB - Squamous cell carcinoma of the upper aero-digestive tract represents 86% of all malignant neoplasms developing in the head and neck. In Italy a comparison of the standardized incidence data shows that such cancer is more frequent in the northern than in the central and southern parts of the country. Males are more often affected than females. After considering the most important risk factors the authors analyze the epidemiology and natural history of cancer of each organ of the head and neck. PMID- 2203225 TI - [Is there a role for immunology in the prevention of malignant tumors of the head and neck?]. AB - The possibility of applying immunological methods to head and neck tumors prevention is discussed. The biological significance of tests evaluating the natural killer activity is reviewed. The IgA serum level in patients at risk for head and neck malignancy is proposed as a screening test. PMID- 2203226 TI - Immunohistochemical analysis of c-erbB-2 oncogene product and epidermal growth factor receptor expression in human urinary bladder carcinomas. AB - Expression of the product of the c-erbB-2 gene, a proto-oncogene related to, but distinct from c-erbB-1 encoding the epidermal growth factor receptor (EGF-R), was investigated in human urinary bladder carcinomas. In addition, levels of EGF-R and transferrin receptor were also analyzed using an immunohistochemical approach, and the results compared with histological pattern and grading, and tumor staging. Increased expression of c-erb B-2 product was found in 32% of cases (7/22), a positive reaction being observed in 60% of transitional cell carcinoma (TCC) Grade 3 lesions (3/5), 20% of Grade 2 TCCs (2/10) and 100% of adenocarcinomas (AC) (2/2), but in none of the cases of squamous cell carcinoma (SCC). Although no statistical correlation with staging was evident, TCCs or SCCs of high grade and stage often showed EGF-R-positive staining, whereas other well differentiated lesions and normal bladder epithelium were generally negative. Most cases of urinary bladder carcinoma were positive for the transferrin receptor, which was not detected in normal bladder. The results thus suggested that a positive reaction for c-erbB-2 product is correlated with TCC histological grading or AC morphology. A high intensity of EGF-R staining in human bladder carcinomas may be associated with poor differentiation and invasion, whereas transferrin receptor expression might reflect tumor growth. PMID- 2203227 TI - Immunoelectron microscopic localization of human type III collagen in human gastrointestinal carcinomas. AB - Ultrastructural immunolocalization of human type III collagen/procollagen was investigated in 28 cases of human gastrointestinal carcinoma by the pre-embedding method using a monoclonal antibody. In addition to immunoreactivity on collagen fibers, amorphous or finely fibrillar immunoreactive substances were observed in the extracellular matrix adjacent to the plasma membrane and in the cisternae of rough endoplasmic reticulum (rER). These substances were considered to represent type III procollagen and/or collagen before fiber formation. Cytoplasmic recesses containing immunoreactive fibers were also observed. These findings related to collagen production were detected in stromal fibroblasts in 16 of 28 cases and in carcinoma cells in six of 28 cases. The positivity rate of these findings was lower in diffuse-type gastric carcinoma. The present study thus clarified further details of collagen production and secretion, and revealed that carcinoma cells may also be involved in the production of stromal collagen in some cases as well as stromal fibroblasts. PMID- 2203228 TI - Glial fibrillary acidic protein immunoreactivity of chondrocytes in immature and mature teratomas. AB - The immunoreactivity of chondrocytes for glial fibrillary acidic protein (GFAP), other intermediate filament proteins and S-100 protein was studied in formalin fixed paraffin-embedded sections. A total of 95 cartilage specimens were examined from five immature teratomas, 12 mature teratomas, and a teratocarcinoma. GFAP immunoreactive chondrocytes were abundant in immature cartilages, and as the cartilages maturated, these chondrocytes decreased and became distributed peripherally. Elastic cartilage had more GFAP-immunoreactive chondrocytes than non-elastic cartilage. GFAP-immunoreactive cartilage was often located close to central nervous tissue. Immunostaining for vimentin and S-100 protein revealed extensive distribution of immunoreactive chondrocytes in immature and mature cartilages, but in mature cartilage, chondrocytes at the center had less vimentin immunoreactivity. GFAP-immunoreactive chondrocytes also showed apparent immunostaining for vimentin. There was no difference in immunohistochemical staining for the alpha and beta subunits of S-100 protein. The immunoreactivities of teratoma cartilage specimens were quite similar to those of respiratory tract cartilage. PMID- 2203229 TI - Paraneoplastic encephalomyelitis. An autopsy case with encephalitis principally confined to the thalamus and associated with pulmonary and gastric cancers. AB - We report an autopsy case of encephalitis principally confined to the bilateral thalamus and associated with pulmonary and gastric cancers. An 81-year-old man exhibiting behavioral abnormalities and progressive somnolence died of pneumonia 11 months after onset. Because the patient had lung cancer and no definite cause of the encephalitis was found, this case was categorized as one of paraneoplastic encephalomyelitis. This may be the first reported case of this condition in which the central nervous system (CNS) lesion was located predominantly in the thalamus. PMID- 2203230 TI - Anaplastic ependymoma of the spinal cord in childhood. A case report. AB - We report a 6-year-old girl with anaplastic ependymoma probably originating in the region of the conus medullaris and probably spreading retrogradely to the region of the interventricular foramen (Monro) through the cerebrospinal fluid (CSF). Since ependymoma of the spinal cord rarely occurs in children, and retrograde spreading is extremely rare, the histological features and mechanism of metastasis of the tumor are discussed. PMID- 2203231 TI - A case report of equivocal neoplasm originating from an apocrine gland on the eyelid. AB - We report a rare case of apocrine neoplasm with malignant potential. The patient, a 29-year-old man, had a nodule 1 cm in diameter on his left upper eyelid which had been growing slowly for several years. It was a cystic lesion, consisting of neoplastic cells of probable apocrine gland or Moll's gland origin. This opinion was based on the histological characteristics, which included eosinophilic cytoplasm accompanied with decapitation secretion, iron granules, and granular depositions which were stained positively with periodic acid-Schiff, with and without diastase digestion. Ferritin was found in their cytoplasm, a feature that has not been reported. It was uncertain whether the neoplasm was benign or malignant, because the cells showed nuclear atypia, characterized by variation in size and hyperchromasia, but lacked the histological features of malignancy, including infiltration into the adjacent tissue and mitosis. PMID- 2203232 TI - In memoriam Endre Grastyan. PMID- 2203233 TI - [Immunodiagnosis of immune thrombocytopenias and their clinical significance]. AB - Immune thrombocytopenia remains a diagnosis per exclusionem. There are no specific clinical symptoms or laboratory parameters to ensure diagnosis. In otherwise caused thrombocytopenias many authors found increased platelet associated immunoglobin (PaIg) and platelet-binding serum immunoglobulin (PbSIg). Methods to determine PaIg and PbSIg are described and their clinical relevance is discussed. Determinations of PaIg and PbSIg with Ig-L-chain-specific ELISA are recommended. They improve diagnostic possibilities to distinguish ITP from nonimmune thrombocytopenias. PMID- 2203234 TI - [Interleukin 1 and hematopoiesis]. AB - Interleukin-1 mediates a broad spectrum of activities in the functional network of cytokines. In addition to its function as an inducer of the acute phase response IL-1 has many effects on hemopoiesis in normal and hematologically impaired organisms. This regulatory function is realized by its ability to stimulate the release of hematopoietic growth factors and by its recruiting property for cell cycles of different hemopoietic progenitors and stem cells. IL 1 acts synergistically with the colony-stimulating factors. PMID- 2203235 TI - Overweight: assessment and management issues. AB - Obesity is associated with an increased risk of coronary artery disease, hypertension, diabetes, hypercholesterolemia, cancer and other conditions. Although generalized obesity is associated with increased risk, the android pattern of body fat distribution may be a more sensitive predictor of coronary artery disease. A gradual weight reduction program, including adherence to a low fat, calorie-restricted diet and participation in daily exercise, is the best approach to reduce weight and body fat. PMID- 2203236 TI - Understanding and preventing injuries. AB - Unintended injuries have become the third most frequent cause of death in the United States, and the relative importance of homicide and suicide has also increased. In recent decades, death rates from highway crashes and fires have fallen, and experience indicates that serious injuries in the workplace can be drastically reduced. Less progress has been made in preventing homicide and suicide. Tasks for the future include more research on the efficacy of preventive interventions, improvement of injury surveillance and prevention programs, and education of children and adults about injury prevention. Family physicians can play an important role in injury prevention efforts. PMID- 2203237 TI - Screening for sexually transmitted diseases. U.S. Preventive Services Services Task Force, Washington, D.C. PMID- 2203238 TI - Radon: counseling patients about risk. AB - Exposure to radon and its decay products has increased as the United States has changed from an outdoor society to a largely indoor society. Radon, which is found primarily in the soil, enters houses and buildings through cracks, holes and pipes in foundation walls and floors. Although radon is suspected of being a significant cause of lung cancer, comparisons with other risk factors cannot yet be made. Radon levels in the home can be measured with commercially available kits. Guidelines for reducing the amount of radon in a home are provided by the U.S. Environmental Protection Agency. PMID- 2203239 TI - Crush injuries of the upper extremity. AB - Massive open wounds are treated conservatively to preserve all viable tissue. Closed crush injuries may require extensive fasciolysis and debridement to treat compartment syndrome. Meticulous cleansing is the primary treatment for open injuries. Compartment syndrome occurs when intracompartmental pressure impairs capillary function and jeopardizes tissue viability. Rhabdomyolysis associated with crush injuries may lead to renal failure. PMID- 2203240 TI - Congestive heart failure. AB - Causes of congestive heart failure include hypertension, coronary artery disease, alcohol abuse and valvular heart disease. Two-dimensional echocardiography with Doppler examination is excellent for identifying valvular heart disease. While noninvasive screening for coronary artery disease may seem cost-effective, the consequences of a missed diagnosis are such that coronary angiography should be strongly considered if there is any suggestion of ischemic heart disease. Medical management primarily consists of vasodilators, diuretics and inotropic agents. Vasodilator therapy may prolong the patient's life. Digoxin and diuretics improve symptoms and hemodynamic abnormalities. With advanced heart failure, adequate control of fluid retention and dyspnea may require diuretic doses associated with azotemia, and systolic blood pressure may have to be maintained at less than 100 mm Hg in spite of postural hypotension. PMID- 2203241 TI - NIH issues statement on disease prevention and treatment with IVIG. PMID- 2203242 TI - Evaluation of methods for enumerating microorganisms in filter samples from highly contaminated occupational environments. AB - Scanning electron microscopy (SEM), light microscopy (LM), epifluorescence microscopy (FM), and culture were used to assess catches of microorganisms in parallel air samples on membrane filters from heavily contaminated working environments that differed in the relative abundance of bacteria, actinomycetes, and fungal spores. Except in pig houses, estimates by SEM and LM were similar, but those by FM and culture were smaller. However, in pig houses, the fluorescent stain enabled bacteria on skin scales, not seen by SEM or LM, to be counted. Although counts obtained by culturing were always smaller than those obtained by SEM or LM, they sometimes exceeded those obtained by FM. Counts suggested that 0.1-68% of bacteria + actinomycetes and 3-98% of fungal spores were viable. However, samples for culturing may have contained larger aggregates than parallel samples collected within a sampling apparatus. All spore types recognized by LM included aggregates--those of bacteria + actinomycetes sometimes exceeding 200 units, while Wallemia sebi spore aggregates were never larger than 3 spores. The size distributions of all types approximated to log-normal, although single spores and small aggregates of bacteria + actinomycetes were perhaps underrepresented. When spores were counted directly on the filter surface, as by SEM and LM, allowance was necessary for heavier deposition of particles near the center of filters by distributing counting fields systematically over the whole filter or a sector of it. Deposition was more uniform in graphite-filled polypropylene filter holders used open-faced. Losses within filter holders and during transportation from sampling site to laboratory were small. The precision of counting spore-containing particles by LM and SEM was better than that of counting individual spores. No such difference was found for FM because many large spore-containing particles were dispersed during preparation. PMID- 2203244 TI - Clinical trials including an update on the Helsinki Heart Study. AB - The incidence of myocardial infarction (MI), sudden death and other clinical manifestations of coronary heart disease can be reduced by lowering the blood cholesterol level. This is now well established by multiple clinical trials using a variety of interventions including diet and lipid-lowering drugs. Dietary studies in Los Angeles and in Oslo, Norway, have induced a reduction in blood cholesterol of between 10 and 15% with correlated reductions in coronary disease of 20 to 50%. Both niacin and clofibrate in separate cohorts demonstrated a significant reduction in new MI during 5 years of treatment in the Coronary Drug Project. Similar reductions in new MI occurred in the World Health Organization Study with clofibrate. However, in this trial and different from all other trials, mortality in the drug-treatment group actually increased. This finding remains unexplained. In the more recent Lipid Research Clinics Coronary Primary Prevention Trial using the bile acid-binding resin cholestyramine, only a 9% reduction in total cholesterol resulted in a highly significant reduction in the major end points--MI and sudden death--as well as in other secondary end points, including the need for coronary artery bypass graft surgery, ischemic changes on exercise electrocardiography and new-onset angina. Recently, another primary prevention trial using gemfibrozil produced a similar reduction in total cholesterol but a much more significant increase in high-density lipoprotein cholesterol. The reduction in coronary heart disease was in excess of 34% and was strongly related to both low-density lipoprotein cholesterol reduction and high density lipoprotein elevation. Combination drug studies have produced larger reductions in total cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203243 TI - Effects of bepridil and CERM 4205 (ORG 30701) on the relation between cardiac cycle length and QT duration in healthy volunteers. AB - Bepridil is a calcium antagonist that prolongs the duration of ventricular repolarization, whereas CERM 4205, another calcium antagonist, seems to be devoid of any effect on QT interval. The aim of this study was to compare the effects of bepridil and CERM 4205 on the QT-RR relation at different heart rates during rest and exercise and the results of pharmacologic tests designed to vary neurovegetative tone. Twelve healthy men (21 to 37 years) participated in a placebo-controlled, randomized, crossover, double-blind study and received either bepridil (200 mg/day twice daily) or CERM 4205 (200 mg/day twice daily), or matching placebo during three 14-day treatment periods at 2-week intervals. Bepridil, but not CERM 4205, caused a significant prolongation of resting QT interval. The RR-QT relation was monoexponential for all subjects during resting and exercising physiologic conditions and remained unchanged after 14 days with placebo or CERM 4205. Bepridil significantly shifted the relation upward, resulting in a rate-dependent QT prolongation that predominated during bradycardia. After isoprenaline, QT no longer adapted to changes in heart rate, whereas atropine resulted in a rate-dependent shortening in QT. These results suggest that bepridil and CERM 4205 exert different effects on ventricular repolarization, since only bepridil significantly prolonged QT duration. Bepridil induced prolongation of QT increased at slow heart rates, which could explain the greater incidence of torsades de pointes in bradycardia. PMID- 2203245 TI - Pharmacotherapy of disorders of plasma lipoprotein metabolism. AB - Pharmacologic intervention for altering plasma lipoproteins is aimed principally at reducing atherogenesis and thereby preventing coronary artery disease. These drugs should be prescribed only after nonpharmacologic interventions (reduction of saturated fat and cholesterol consumption, weight reduction, aerobic exercise, cessation of cigarette smoking) have failed to achieve an adequate effect. The plasma concentration of the atherogenic low-density lipoprotein (LDL) may be reduced in hypercholesterolemic patients by increasing hepatic LDL receptor synthesis (bile acid sequestering resins, 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors) or by reducing hepatic very low density lipoprotein synthesis (gemfibrozil, nicotinic acid). LDL concentration may also be reduced by treatment with one of the fibrates (e.g., fenofibrate). Several classes of lipid lowering drugs also increase the plasma high-density lipoprotein (HDL) cholesterol concentration. In the case of the fibrates, this appears to be principally mediated through an increase in lipoprotein lipase activity. Gemfibrozil additionally stimulates apolipoprotein AI synthesis. The increase in HDL cholesterol produced by nicotinic acid is due primarily to decreased clearance of HDL particles from the circulation. The increase in HDL concentration produced by gemfibrozil was shown in the Helsinki Heart Study to make a major contribution to a reduced incidence of coronary artery disease, independently of that made by the decrease in LDL. The Cholesterol-Lowering Atherosclerosis Study demonstrated that combined therapy with a resin (colestipol) and nicotinic acid can reduce the progression of coronary atherosclerosis and the development of graft lesions in patients who have undergone coronary artery bypass graft surgery. PMID- 2203246 TI - Interrelationship of triglycerides with lipoproteins and high-density lipoproteins. AB - Triglycerides are transported by the largest and most lipid-rich of the lipoprotein particles, namely, chylomicrons and very low density lipoproteins (VLDL). These particles are buoyant because of the high triglyceride content, which makes up approximately 90% by weight of the chylomicron and 70% by weight of the VLDL. The chylomicron transports exogenous or dietary fat and cholesterol, whereas VLDL transports endogenous triglyceride and cholesterol in lipoproteins synthesized and secreted by the liver. Both chylomicrons and VLDL are hydrolyzed at the capillary surface by the enzyme lipoprotein lipase. Lipoprotein lipase catalyzes the hydrolysis of triglyceride in the lipid core of these particles, producing smaller particles known as remnants. We currently believe the remnants are atherogenic and that this is one reason why hypertriglyceridemia may predispose to coronary artery disease. Chylomicron remnants are recognized and removed by hepatic receptors that contain apolipoprotein (apo) E. The rate of clearance of remnant particles depends on which subfraction of apo E is present. Particles containing apo EII are removed more slowly than those with apo EIII and EIV. The dietary cholesterol from the chylomicron remnant particles is thought to down-regulate the hepatic low-density lipoprotein (LDL) receptors. VLDL remnants, also called intermediate-density lipoprotein (IDL), contain apo E and may be removed by the liver through the LDL or B/E receptor. The decrease in activity of these receptors results in apparent oversynthesis of LDL, the end-product of VLDL and IDL metabolism. LDL is the major cholesterol carrier, followed by high density lipoprotein (HDL).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203247 TI - High-density lipoprotein cholesterol and coronary artery disease: survey of the evidence. AB - The epidemiologic evidence linking high-density lipoprotein (HDL) levels with coronary artery disease (CAD) is persuasive. Case-control studies have shown CAD patients to have lower HDL levels than control subjects. Several large-scale, observational epidemiologic studies in the United States and abroad have shown a strong independent inverse relation between HDL and CAD. Women have a lower incidence of CAD than men of the same age; this has been attributed to their higher HDL levels. Postmenopausal women taking estrogen replacement therapy have higher HDL and lower low-density lipoprotein (LDL) levels, and a much lower incidence of CAD. Statistical analysis suggests that much of this is attributable to HDL levels. In several clinical trials, reduced levels of total or LDL cholesterol have been accompanied by increased HDL levels. Cox proportional hazards analysis suggests that the increment in HDL levels made an independent contribution to the reduction in CAD risk. In several angiographic studies, the increase in HDL may have contributed to the decreased progression, increased stabilization and possible regression of coronary lesions. Despite this range of impressive evidence, a number of unresolved issues have prevented the emergence of a consensus regarding the prevention of CAD by increasing HDL levels. Between population comparisons of HDL and CAD do not match the within-population relations. Animal research on the relation between HDL, atherogenesis and CAD has been relatively scanty. Although much evidence suggests that reverse cholesterol transport partially explains the protective effect of HDL, there are still doubts as to its role. Problems with measurement of HDL have inhibited widespread recommendations for its use in prevention programs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203248 TI - High-density lipoprotein, low-density lipoprotein and coronary artery disease. AB - Lipoprotein cholesterol data from the Framingham Heart Study show that low density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels are important in determining risk for coronary artery disease (CAD). Increased LDL and decreased HDL cholesterol levels are associated with an increase in CAD. Such relations are independent of the usual coronary risk factors, such as cigarette use and hypertension. A 1% greater LDL value is associated with slightly more than a 2% increase in CAD over 6 years; a 1% lower HDL value is associated with a 3 to 4% increase in CAD. Even at total cholesterol levels less than 200 mg/dl, lower HDL levels are associated with increased myocardial infarction rates in both men and women. Death from CAD is increased when HDL levels are low, but there is no such relation between HDL level and cancer death. Triglyceride levels were associated with CAD in Framingham men and women, but the association was no longer significant in men after adjustment for HDL levels. The major determinants for greater HDL levels in Framingham participants included female sex, estrogen use, leanness, greater alcohol intake, exercise, abstinence from smoking and lack of diuretic or beta-blocker use. PMID- 2203249 TI - Anabolic effects of growth hormone in obese diet-restricted subjects are dose dependent. AB - In previous studies growth hormone (GH) injections [0.1 mg/kg ideal body wt (IBW) every other day] produced significant increases in plasma insulin-like growth factor I (IGF-I) concentrations and nitrogen retention, which were attenuated when 12 kcal/kg IBW was ingested. The present study was done to determine whether doubling the GH dose would enhance its anabolic effects and facilitate fat loss. Eight women (33-83% over IBW) were fed 12 kcal/kg IBW for 14 wk. They received GH or vehicle injections, each for 5 wk during either weeks 2-6 or 9-13. GH improved nitrogen balance (GH, 3.6 +/- 123.2 mmol/d; vehicle, -132.0 +/- 117.9 mmol/d; means +/- SD; p less than 0.001). Plasma IGF-I increased from 32.1 +/- 9.6 to 79.4 +/- 22.1 nmol/L by day 5 of GH (p less than 0.001) and remained elevated until GH injections were discontinued. No significant effect of GH on mean body fat loss was observed. GH can induce significant anabolic responses even when caloric intake is decreased to 12 kcal/kg IBW. The degree and duration of these anabolic responses are dependent on the GH dose given. PMID- 2203250 TI - Ingestion of different types of fat in the evening meal does not affect metabolic responses to a standard breakfast. AB - High-fat diets produce insulin resistance, but it is not known how quickly changes become evident or whether different types of fat produce different responses. The aim of this study was to determine whether a high-fat evening meal affected glucose response to a standard breakfast 12 h later. On six occasions eight weight-stable subjects consumed a standard evening meal (109 g carbohydrate, 27 g protein, 6 g fat, and 10.6 g fiber) that was either unsupplemented or supplemented with 41 g fat (safflower oil, olive oil, butter, or medium-chain triglyceride) or 75 g carbohydrate followed by a standard breakfast. Glucose, insulin, and free fatty acid responses were measured over 3 h. There were no differences in metabolic responses to the standard breakfast after the different evening meals, indicating that a single high-fat meal has no deleterious effects on carbohydrate metabolism 12 h later, regardless of the type of fat ingested. PMID- 2203251 TI - Quantitative changes in dietary fat intake and serum cholesterol in women: results from a randomized, controlled trial. AB - We compared observed and predicted changes in serum cholesterol in women with mammographic dysplasia who participated for 12 mo in a randomized, controlled trial of a low-fat, high-carbohydrate diet, in which total fat intake was reduced from an average of 37% of calories to 21% and carbohydrate intake increased from 44% to 52% of calories. Changes observed in serum cholesterol were greater than those predicted (by the formulas of Hegsted and Keys) for subjects with initial serum cholesterol values in the upper tertile of the population, were not significantly different from those predicted for subjects with baseline values in the middle tertile, and were significantly less than those predicted for subjects with initial values in the lower tertile. These results show that the usefulness of serum cholesterol as a marker of change in dietary fat intake in women depends on the distribution of serum cholesterol values in the population studied. PMID- 2203253 TI - Plasma concentrations of carotenoids after large doses of beta-carotene. AB - Plasma concentrations of beta-carotene were determined in healthy men ingesting 180 mg beta-carotene/d during studies on the effects of beta-carotene on sunburn prevention. This dose is also used in the treatment of light-sensitive skin diseases. beta-carotene concentrations were found to reach a plateau in 1.5 to 4 wk, although there was much individual variation in the actual serum concentrations achieved. Carotenodermia was present in most subjects. No evidence of toxicity was found, confirming the findings of previous photosensitivity prevention studies, which also reported no significant toxicity attributable to beta-carotene. PMID- 2203252 TI - Effects of fish oil on serum lipids in men during a controlled feeding trial. AB - Effects of fish-oil (FO) feeding on serum lipids were investigated in a 42-d controlled diet study. Fifteen healthy male college students were assigned to one of three groups: control (0 g FO); 5 g FO, supplying 2 g n - 3 (omega-3) fatty acids (FAs); or 20 g FO, supplying 8 g n - 3 FAs. In an initial 7-d period subjects consumed a basal diet with no FO. Then FO replaced an equivalent amount of margarine for 5 wk. FO feeding significantly (p less than 0.05) decreased the serum n - 6 FAs, linoleic acid, eicosatrienoic acid, and arachidonic acid. A significant increase in the n - 3 FAs, eicosapentaenoic acid and docosahexaenoic acid, was noted in serum, platelet, and neutrophil phospholipids. The 20-g-FO group showed a 30% decrease (p less than 0.01) in triglycerides after 2 wk FO with no further decrease observed. Thus, 20 g FO produced changes in both FA patterns and triglyceride concentrations whereas 5 g FO produced changes in FA patterns only. Neither FO amount resulted in significant changes in total or HDL cholesterol, apolipoprotein A-I, or apolipoprotein B-100. PMID- 2203254 TI - Effect of dietary protein on bed-rest-related changes in whole-body-protein synthesis. AB - To determine whether increasing dietary protein could exert a beneficial effect on bed-rest-related protein catabolism, two groups of normal subjects were subjected to 7 d of bed rest while taking isocaloric diets containing either 0.6 or 1.0 g protein.kg body wt-1.d-1. Whole-body-leucine turnover, leucine oxidation, and nonoxidative leucine disappearance were measured by use of a constant infusion of 1-13C-leucine. Before bed rest, the higher-protein diet resulted in a 14% decrease in whole-body-leucine turnover and a 28% decrease in leucine oxidation, but net nonoxidative leucine disappearance was not different on the two diets. A 24% decrease in nonoxidative leucine disappearance was seen in subjects assigned to the lower-protein diet, who had been on bed rest, but on the higher-protein diet, leucine kinetics were unchanged by bed rest. Bed rest does not cause an increase in whole-body-protein breakdown, but decreased whole body-protein synthesis is demonstrable when dietary protein is low. This decrease is prevented by a higher dietary amount of protein. PMID- 2203255 TI - Water volume and consumption time: influence on the glycemic and insulinemic responses in non-insulin-dependent diabetic subjects. AB - The present study was carried out to see if either the volume of water or the duration of ingestion time influence the postprandial blood glucose and insulin responses in non-insulin-dependent diabetic (NIDDM) subjects. Small test meals containing 40 g carbohydrate as rye bread (100 g) with butter (10 g) and tomatoes (75 g) were given to 10 NIDDM subjects. The meals were taken in random order with either 90 or 600 mL tap water. The meal with 90 mL tap water was ingested over 10 and 30 min. The glycemic responses to isocaloric meals of large and small volumes were similar (338 +/- 56 vs 384 +/- 67 mmol/L.240 min) as were the insulinemic responses (29,424 +/- 6512 min vs 27,140 +/- 6548 mumol/L.240 min). An extension of eating time from 10 to 30 min did not alter the glycemic (384 +/- 67 vs 370 +/ 54 mmol/L.240 min) or the insulinemic response (27,140 +/- 6548 vs 35,670 +/- 10,245 mumol/L.240 min) in the NIDDM patients. PMID- 2203256 TI - Insulin response and glycemic effects of meals in non-insulin-dependent diabetes. AB - Glycemic and hormonal responses to two breakfast mixed meals were studied in six obese subjects with NIDDM. The study evaluated a high-glycemic-effect (HGE) and a low-glycemic-effect (LGE) meal, each with approximately 600 kcal and 12% protein, 15% fat, and 73% carbohydrate. Plasma insulin and counterregulatory hormones were measured at baseline and at 30-min intervals for 5 h after meals. Mean fasting plasma glucose and insulin concentrations were similar before both studies: for the LGE meal, 11.9 +/- 1.8 mmol/L and 261.9 +/- 50.1 pmol/L; for the HGE meal, 11.9 +/- 2.0 mmol/L and 262.6 +/- 43.1 pmol/L. Peak plasma glucose concentrations were approximately 25% lower with the LGE meal and the area under the glucose curve was 63% of that obtained for the HGE meal (p less than 0.05). Although the integrated insulin responses of the two meals did not differ, the peak occurred 60 min earlier in the LGE meal (p less than 0.05). The LGE meal may produce a lower glycemic response, in part because of earlier insulin secretion. PMID- 2203257 TI - Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects. AB - The effect of vitamin E supplementation on the immune response of healthy older adults was studied in a double-blind, placebo-controlled trial. Subjects (n = 32) resided in a metabolic research unit and received placebo or vitamin E (800 mg dl alpha-tocopheryl acetate) for 30 d. Alpha-tocopherol content of plasma and peripheral blood mononuclear cells (PBMCs), delayed-type hypersensitivity skin test (DTH), mitogen-stimulated lymphocyte proliferation, as well as interleukin (IL)-1, IL-2, prostaglandin (PG) E2, and serum lipid peroxides were evaluated before and after treatment. In the vitamin E-supplemented group 1) alpha tocopherol content was significantly higher (p less than 0.0001) in plasma and PBMCs, 2) cumulative diameter and number of positive antigen responses in DTH response were elevated (p less than 0.05), 3) IL-2 production and mitogenic response to optimal doses of concanavalin A were increased (p less than 0.05), and 4) PGE2 synthesis by PBMCs (p less than 0.005) and plasma lipid peroxides (p less than 0.001) were reduced. Short-term vitamin E supplementation improves immune responsiveness in healthy elderly individuals; this effect appears to be mediated by a decrease in PGE2 and/or other lipid-peroxidation products. PMID- 2203258 TI - Identification of the base-pair substitution responsible for a human acid alpha glucosidase allele with lower "affinity" for glycogen (GAA 2) and transient gene expression in deficient cells. AB - The lysosomal enzyme termed acid alpha glucosidase (GAA), or acid maltase, is genetically polymorphic, with three alleles segregating in the normal population. The rarer GAA 2 allozyme has a lower affinity for glycogen and starch but not for lower-molecular-weight substrates. The GAA 2 allozyme can be detected by "affinity" electrophoresis in starch gel, since the lower affinity for the starch matrix results in a more rapid migration to the anode. Previously, we have isolated and sequenced the cDNA for GAA and transiently expressed the cDNA in deficient fibroblasts. In order to determine the molecular basis for the GAA 2 allozyme, we constructed a cDNA and a genomic DNA library from a GAA 2 cell line and determined the nucleotide sequence of the coding region. Only a single base pair substitution of an A for a G at base-pair 271 was found, resulting in substitution of asparagine for aspartic acid at codon 91. This amino acid substitution is consistent with the more basic pI of the GAA 2 enzyme. The base pair substitution also abolishes a Taq-I site, predicting the generation of a larger DNA fragment. This larger Taq-I fragment was also seen in two other individuals expressing the GAA 2 allozyme. A 5' fragment containing the base-pair substitution was ligated to the remaining 3' cDNA from a GAA 1 allele and cloned into an expression vector, and the hybrid cDNA was transiently expressed in SV40 transformed GAA-deficient fibroblasts. The enzyme activity exhibited the altered mobility of the GAA 2 allozyme, as demonstrated by electrophoresis in starch gel.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203259 TI - Hereditary fructose intolerance caused by a nonsense mutation of the aldolase B gene. AB - The nucleotide sequence of a patient's aldolase B gene was determined and showed a substitution of a single nucleotide (C----A) at position 720 in the coding region, which resulted in the 240th amino acid, a cysteine, being changed to a stop codon (TGC----TGA). By an allele-specific oligonucleotide probe and polymerase chain reaction, the patient was shown to be homozygous for the mutation. To examine whether this mutation causes functional defect of the enzyme, the activity of the aldolase B from the patient, expressed in Escherichia coli by using expression plasmid, was measured. No activity was observed, and the predicted product was recovered from E. coli expression plasmid, indicating that this nonsense mutation was the cause of aldolase B deficiency. PMID- 2203260 TI - Extragenital Mycoplasma hominis infections in adults. AB - PURPOSE: To heighten awareness of the role of Mycoplasma hominis as an extragenital pathogen in adults. PATIENTS AND METHODS AND RESULTS: Patients ranged in age from 14 to 76 years. Thirteen patients were immunosuppressed, including nine organ transplant recipients; three were receiving steroids, and two had an underlying malignancy. The remainder were immunocompetent. Thirteen patients had prior surgery at or near the site of infection. M. hominis was isolated from normally sterile sites such as blood or cerebrospinal, pleural, abdominal and joint fluids, and bone. Non-sterile sites of isolation included surgical wounds and pulmonary secretions. The organism was detected in anaerobic cultures of clinical specimens sent to the laboratory for routine bacteriologic culture. Gram stains of fluids or wound drainage revealed neutrophils but no bacteria. Anti-mycoplasmal therapy was effective in eradicating the organism in 13 of 15 patients who were treated. Of those in whom treatment failed, one patient had an antibiotic-resistant isolate and the other had M. hominis isolated from the lung at postmortem after just 2 days of therapy. CONCLUSION: Our experience suggests that significant infections due to M. hominis, although uncommon, are not rare, and methods to isolate and identify this organism should be available for general adult medical and surgical populations. PMID- 2203261 TI - Marked spontaneous improvement in ejection fraction in patients with congestive heart failure. AB - PURPOSE: The overall prognosis for patients with congestive heart failure is poor. Defining specific populations that might demonstrate improved survival has been difficult. We therefore examined our patient database for patients with congestive heart failure who demonstrated sustained improvement in left ventricular function and associated resolution of signs and symptoms of congestive heart failure. PATIENTS AND METHODS: We identified 11 patients with severe congestive heart failure (average ejection fraction 21.9 +/- 4.23% (+/- SD) who developed spontaneous, marked improvement over a period of follow-up lasting 4.25 +/- 1.49 years. All 11 patients were initially symptomatic with exertional dyspnea and fatigue for a minimum duration of 3 months. They form a subset of a larger group of 97 patients with chronic congestive heart failure that we have followed with sequential ejection fraction measurements. All 11 patients were treated with digitalis diuretics, and either converting-enzyme inhibitors or a combination of isosorbide dinitrate and hydralazine. Ten of the 11 patients had a history consistent with chronic alcoholism, and each reportedly abstained from alcohol during follow-up. RESULTS: During the follow-up period, the average ejection fraction improved in 11 patients from 21.9 +/- 4.23% to 56.64 +/- 10.22%. Late follow-up indicates an average ejection fraction of 52.6 +/- 8.55% for the group. Congestive heart failure resolved in each case. CONCLUSIONS: We conclude that selected patients with severe congestive heart failure can markedly improve their left ventricular function in association with complete resolution of heart failure. This appears to be particularly evident in those patients with chronic alcoholism who subsequently abstain. PMID- 2203262 TI - Effects of sulindac and naproxen on prostaglandin excretion in patients with impaired renal function and rheumatoid arthritis. AB - PURPOSE: The purpose of the current investigation was to study the influence of sulindac and naproxen on renal function and urinary excretion of the stable hydration product of prostacyclin, 6-keto-PGF1 alpha, in patients with arthritis and impaired renal function. PATIENTS AND METHODS: In a placebo-controlled, double-blind, cross-over design, the effects of 7 days of oral sulindac 200 mg twice a day were compared with naproxen 500 mg in the morning and 250 mg in the evening in 10 patients with polyarthritis and stable impaired renal function. Inulin and para-amino-hippurate sodium were used to calculate glomerular filtration rate and renal plasma flow. The excretion rate of 6-keto-PGF1 alpha was measured in urine collected overnight. After patients ingested drugs in the morning, urine was collected in fractions by spontaneous voiding. Venous blood samples were drawn repeatedly for assay of electrolytes, creatinine, proteins, hormones, and drugs. Grip strength and Ritchie articular index were recorded as indicators of symptomatic antiarthritic effectiveness. RESULTS: Naproxen decreased urine levels of 6-keto PGF1 alpha by 59% (p less than 0.01). Sulindac had no effect on renal prostaglandin excretion. Naproxen reduced the glomerular filtration rate and renal plasma flow by 18% (p less than 0.05) and 13% (p less than 0.05), respectively, while no significant change was observed during the sulindac treatment periods. Serum levels of creatinine and complement factor D were unaffected by either drug. Plasma renin activity decreased during naproxen and sulindac treatments by 38% (p less than 0.05) and 22% (p less than 0.05). No significant change in plasma aldosterone was observed during the two drug treatments, but urinary aldosterone declined significantly (p less than 0.05) by 34% with naproxen. Albuminuria decreased (p less than 0.05) during both naproxen (41%) and sulindac treatment (72%), while the albumin/creatinine clearance ratio decreased by 59% (p less than 0.05) only during treatment with sulindac. N-acetyl beta-D-glucosaminidase in urine was not changed by either drug. Sulindac and naproxen had no discernible effects on base excess, excretion of water, sodium, or potassium, or on osmolal clearance. However, serum potassium increased slightly but significantly (p less than 0.01) during treatment with naproxen. Sulindac sulfide, the active metabolite of sulindac, could not be traced in the urine from any of the patients. Mean arterial blood pressure declined significantly (p less than 0.05) during sulindac treatment but did not change during treatment with naproxen. Both drugs produced equal clinical improvement as measured by grip strength and the Ritchie articular index. CONCLUSION: The results suggest that when sulindac and naproxen are given in clinical equipotent doses to patients with impaired renal function, sulindac does not affect renal prostaglandin synthesis or renal function, whereas naproxen induces suppression of renal prostaglandin synthesis and a further decrease in renal function. PMID- 2203263 TI - State-of-the-art conference on azidothymidine therapy for early HIV infection. PMID- 2203264 TI - Prolonged ambulatory esophageal pH monitoring in the evaluation of gastroesophageal reflux disease. AB - Gastroesophageal reflux disease is a common problem that frequently presents with atypical complaints including nausea, hiccups, globus sensation, chest pain, hoarseness, coughing, or various pulmonary complaints. Diagnosis may be difficult, as these patients often do not have radiographic or endoscopic evidence of esophagitis. In these difficult cases, prolonged esophageal pH monitoring provides an accurate method of quantitating acid reflux parameters and correlating symptoms with reflux episodes in an outpatient setting. Current equipment is compact, durable, and not difficult to use or extremely expensive. Data analysis, with a particular emphasis on acid-exposure time (total, upright, supine), reliably discriminates between abnormal and normal subjects but it is not a perfect "gold standard" for gastroesophageal reflux disease. Indications for esophageal pH monitoring include: (1) atypical symptoms of acid reflux with normal endoscopy, (2) typical reflux symptoms unresponsive to medical therapy, and (3) the follow-up of reflux disease after either medical or surgical therapy. This test is currently performed primarily by gastroenterologists, but we believe many other groups may find this technology helpful. To meet these expanding applications, test refinements are necessary, particularly easier methods of placing the pH probe and better standards for defining abnormal pH parameters in older patients. The future for esophageal pH monitoring is bright. This technology has the potential to do for the diagnosis of gastroesophageal reflux disease what endoscopy has done for the diagnosis of peptic ulcer disease. PMID- 2203265 TI - Successful use of granulocyte-macrophage colony-stimulating factor in patients with acute lymphocytic leukemia. PMID- 2203266 TI - Treatment of Sweet's syndrome. PMID- 2203267 TI - Saphenous vein in situ bypass. AB - Revascularization of the ischemic diabetic extremity presents a significant diagnostic and technical challenge. The in situ saphenous bypass provides a conduit that allows revascularization to arteries at the ankle and proximal foot. Evaluation of the distal circulation, the adequacy of the saphenous vein, and routine follow-up after bypass, along with the operative procedure, are described. Balloon inflow occlusion arteriography, duplex mapping of the saphenous vein, operative technique, and follow-up protocol are discussed. PMID- 2203268 TI - Local excision of rectal carcinoma. AB - Sixteen published series were reviewed in which local excision was used as definitive treatment for patients with invasive rectal carcinoma located within 6 cm of the anal verge. Ninety-four percent of tumors were T1 or T2 adenocarcinomas with no identified regional metastases. Five-year cancer-specific survival was 89%. Local recurrence was 19%, although more than half of these patients were cured with additional surgery. These results were comparable with those for historical controls treated with abdominoperineal resection (APR). Four pathologic features of the surgical specimen were analyzed to assess their correlation with patient outcome. Positive surgical margins, poorly differentiated histology, and increasing depth of bowel wall invasion were associated with increased local recurrence and decreased survival. Tumor size greater than 3 cm was not a significant factor. When criteria for appropriate patient selection are followed, local excision may provide survival and recurrence rates comparable with those achieved with APR with less morbidity and operative mortality. PMID- 2203269 TI - Noninvasive measurement of regional blood flow in man. AB - Regional blood flow in man is ideally measured by techniques that are noninvasive, accurate, and can measure flow repetitively with comparative ease. Although numerous noninvasive techniques are available, no single method records blood flow accurately in every location. The neophyte investigator is often faced with a confusing array of methods and can spend considerable time searching for the ideal one. This paper presents current methods available to the clinical or metabolic researcher and comments on the strengths and limitations of each method. It is hoped that this will allow more rapid selection of a flow measurement method that is tailored to each individual's need. PMID- 2203270 TI - Histogenesis of recurrent nevus. AB - We report an immunohistochemical study of eight cases of recurrent nevi. S-100 protein-positive and Factor XIIIa-negative fibroblast-like cells were found in and around the scar. Some cells were adjacent to vessels whereas others were dispersed in the fibrotic tissue. These cells probably represent entrapped or migrating nevus cells originating from the deep, unremoved portion of the nevus. PMID- 2203271 TI - A critique of current classifications of vulvar diseases. AB - Several classifications of vulvar diseases have been proposed, but none of them is either consistent internally or applicable clinically and histopathologically. Ambiguous and even inexplicable terms such as "atypical epithelial hyperplasia (dysplasia)", "vulvar dystrophy," "vulvar atypia," "atrophic dystrophy," "mixed dystrophy," and "vulvar intra-epithelial neoplasia" prevent clinicians and histopathologists from communicating effectively with each other. In addition, these terms have different meanings to dermatologists, pathologists, and gynecologists--if indeed they have any meaning at all. If that maelstrom of confusion is to be avoided, diagnoses by histopathologists must be made in the language of clinical medicine. Only then will clinicians be able to understand those diagnoses and thereby manage patients rationally. For example, if findings by conventional microscopy are those of squamous-cell carcinoma in situ of the vulva, the diagnosis of pathologists should be Bowen's disease or bowenoid papulosis and not "vulvar intra-epithelial neoplasia"--a term that is just as applicable to seborrheic keratosis as it is to Bowen's disease and bowenoid papulosis. PMID- 2203272 TI - Melanocytes of a melanocytic nevus in a lymph node from a patient with a primary cutaneous melanoma associated with a small congenital nevus. AB - Aggregates of melanocytes within the parenchyma of a supraomohyoid lymph node were found in a lymph node dissection from a 52-year-old woman who had a primary cutaneous melanoma that had arisen in association with a small congenital nevus. The melanocytes in the lymph node were interpreted to be those of a benign melanocytic nevus, and not those of malignant melanoma, based on similarities in morphologic features and immunohistochemical staining between the melanocytes in the node and those in the cutaneous congenital nevus. PMID- 2203274 TI - [Pathogen spectrum and pathways of infection at an intensive care burn unit]. AB - Coagulase-negative staphylococci have gained increasing importance in burns, whereas interest is no longer focussed on Pseudomonas bacteria. By means of microbiological analysis of swabs taken from patients, environment and staff, we trailed the routes of infection in an intensive-care unit for burns. Analysis of patients: In 27 out of 11 patients the same biotype of Staphylococcus epidermidis could be identified; 22 of these occurred in swabs from wounds. The phagotypification of Staphylococcus aureus showed the same phagotype in 28 out of 41 swabs taken from infected wounds of 10 patients. The pathogen mostly caused the destruction of already healed grafts in a later phase of the treatment. Further microbiological analysis showed a severe infestation of the patients by enterococci. Analysis of environment: Here, greatly increased counts of coagulase negative staphylococci of the same lysotype as in the patients could be demonstrated. Analysis of staff: The naso-pharyngeal area is of minor importance in the spreading of germs, whereas that of protective clothing and especially the hands should be considered to be more crucial. Regular environmental tests enable rapid detection of hygienic errors so that appropriate countermeasures can be taken. PMID- 2203273 TI - [Propofol infusion for sedation in regional anesthesia. A comparison with midazolam]. AB - 50 non-premedicated ASA class I or II patients were allocated randomly into two groups and received either a variable infusion of propofol or midazolam for sedation during orthopaedic surgery with regional blockade. To achieve a well sedated patient with eyes closed and able to follow commands, the dose requirements for propofol were 1.25 mg/kg +/- 0.5 as a loading dose followed by a mean infusion rate of 3.17 mg kg-1 h-1 +/- 1.4 and for midazolam 0.073 mg/kg +/ 0.02 and 0.074 mg kg-1 h-1 +/- 0.14. Steady-state plasma concentrations of propofol averaged 1.23 micrograms/kg +/- 0.75 and of midazolam 134 ng/ml +/- 62. Recovery was significantly shorter for propofol: 3.42 +/- 2.5 versus 8.05 min +/6.2 for midazolam. Perioperative cooperation was similar in both groups providing good or excellent conditions in 76% with propofol and in 52% with midazolam. 2h after discontinuation of the infusion 92% of the propofol patients were alert, while 36% of the midazolam were sleeping again. Cardiovascular effects of both drugs were minimal; however significant respiratory depression and/or airway obstruction developed in both groups (propofol 48%, midazolam 52%) requiring therapeutic intervention. Additional undesirable effects were: severe cough (propofol 40%, midazolam 20%), inadvertent movements (propofol 36%, midazolam 24%), confusion (propofol 24%, midazolam 20%), euphoria (propofol 44%), pain on injection (propofol 32%). The results of the study indicate that both drugs are useful and controllable sedative agents for surgery under regional anaesthesia, provided that measures for continuous monitoring of respiration and emergency care are guaranteed. PMID- 2203275 TI - [Traumatic blindness and decompression of the optical canal by the naso-sinusal route]. AB - By analyzing the pathophysiology for post-traumatic amaurosis and both the diagnosis and surgical decompression of the canalicular segment of the optic nerve with transethmoidosphenoidal approach a study of the historical evolution of the extracranial techniques for its decompression, as well as several treatments, complications and guidelines for patients diagnosed of post-traumatic blindness, is carried out. PMID- 2203276 TI - [Epidemiological factors in allergic rhinitis. Review and personal comparative study of rural and urban populations in the province of Barcelona]. AB - After a bibliographical perusal of the subject, the AA. deals with the main epidemic factors of allergic rhinitis such as frequency, age, sex, race, geographical differences, climatic and seasonal influences, social and economic status, date of birth, duration, links with asthma bronchial and other allergies, etc. The contribution of the AA. is the personal comparative investigation done, during a 3 years period in rural and urban populations of the province of Barcelona. PMID- 2203278 TI - Electron microscopic evaluation of the occurrence of matrix vesicles in cartilage. AB - Troubled by variations in the descriptions of shape, appearance, and content of matrix vesicles and the conflicting reports of increased numbers of vesicles in the mineralizing regions of the growth plate contrasted with larger numbers in the resting zone, we embarked on a review of matrix vesicles in the growth plate using a comparison of different fixation techniques. We found matrix vesicles resembling cell debris at all levels of the growth plate, with no particular association with mineral. Lipid bodies surrounded by a membrane of proteoglycan have also been seen in large numbers. The cell debris-like matrix vesicles have been the common finding in reports of digested centrifuged cartilage and may represent cytoplasmic processes. Lipid bodies surrounded by proteoglycan may be similar to the membrane-bound vesicle described by Ali (Fed. Proc., 35:135-142, 1987) and by Bonucci (Clin. Orthod., 78:108-133, 1971). PMID- 2203277 TI - [Hormones and the nasal mucosa. A bibliographic review]. AB - The development and activity of the nasal mucosa are influenced by many hormonal substances. In this work we realize a bibliographical review about the effect of adrenaline, thyroid hormones, corticosteroids and sex hormones on the nasal respiratory mucous membrane. We emphasize the clinic consequences. PMID- 2203279 TI - Are Doppler-detected venous emboli during cesarean section air emboli? AB - The incidence of venous emboli during cesarean section was studied using simultaneous precordial ultrasonic Doppler monitoring and two-dimensional echocardiography. Forty-nine patients receiving either general or continuous epidural anesthesia in the horizontal position were monitored with both Doppler monitoring and echocardiography. There was excellent correlation between the embolic events detected by Doppler monitoring and by echocardiography (kappa value = 1). The incidence of venous emboli was 29% (14/49). The venous emboli detected by Doppler monitoring were indeed air emboli, not amniotic fluid or thromboemboli, as illustrated by their echocardiographic appearance. PMID- 2203280 TI - The Wood Library-Museum's 1858 edition of John Snow's On chloroform and other anaesthetics. AB - The original 1858 edition of John Snow's On Chloroform and Other Anaesthetics, from which came the Wood Library-Museum of Anesthesiology reprints in 1971 and 1989, was donated to the Wood Library-Museum by Ralph Waters of Madison, Wisconsin, in 1967. The book contains a message of appreciation to Waters, dated October 1937, with the signatures of J. Blomfield, Charles King, and R.R. Macintosh as representatives of anesthesiology in England. Correspondence exists in the archives of the University of Wisconsin-Madison between Macintosh, Professor of Anaesthetics in Oxford, and Waters, Associate Professor in Madison. This reveals that Waters, during his visit to England in 1936, inspired British anesthetists to discover more of Snow's early contributions to anesthesiology, even though Waters himself did not possess On Chloroform and Other Anaesthetics. King, a manufacturer of anesthetic equipment, found a copy in the hands of Blomfield, an anesthetist at St. George's Hospital, London, where John Snow had worked. It was this copy that they presented to Waters, and that was delivered to Waters by hand when Waters' resident, Ivan Taylor, returned from Oxford to Madison. Blomfield's ownership of the book, in addition to his position as president of the Association of Anaesthetists of Great Britain and Ireland, explains why the inscription is in his handwriting. PMID- 2203281 TI - Continuous alfentanil infusion for stereotactic brain biopsy. PMID- 2203282 TI - Effect of epinephrine on intrathecal fentanyl analgesia in patients undergoing postpartum tubal ligation. AB - Eighty women receiving spinal anesthesia for postpartum tubal ligation were entered into a double-blind, randomized protocol studying the effects of epinephrine on intrathecal fentanyl-induced postoperative analgesia. All patients received 70 mg hyperbaric lidocaine with either 0.2 mg epinephrine (LE), 10 micrograms fentanyl (LF), epinephrine and fentanyl (LFE), or 0.4 ml saline (L). Onset and regression of anesthesia, degree of intraoperative comfort, incidence of pruritus, and extent of postoperative analgesia were evaluated. The simultaneous administration of epinephrine and fentanyl prolonged the duration of complete analgesia (137 +/- 47 min (LFE); 76 +/- 32 min (LE); 85 +/- 44 min (LF); 65 +/- 36 min (L)) and the duration of effective analgesia (562 +/- 504 min (LFE); 227 +/- 201 min (LE); 203 +/- 178 min (LF); 198 +/- 342 min (L)). Administration of epinephrine decreased the incidence of pruritus associated with intrathecal fentanyl (1/18 (LFE); 1/21 (LE); 8/19 (LF); 2/19 (L)). PMID- 2203283 TI - Pharmacology and therapeutic applications of cocaine. PMID- 2203284 TI - Epidural injection of a phenol-containing ranitidine preparation. PMID- 2203286 TI - Prolonged alfentanil effect following erythromycin administration. PMID- 2203285 TI - Allergic shock to latex and ethylene oxide during surgery for spinal bifida. PMID- 2203287 TI - Latent myotonic dystrophy: the cause of hydramnios and an increase in serum creatine kinase concentration. PMID- 2203288 TI - Doppler-guided axillary block in a burn patient. PMID- 2203289 TI - The effect of oral midazolam on anxiety of preschool children during laceration repair. AB - Preschool age children often experience marked anxiety and physical pain during laceration repair. Locally infiltrated anesthetics or topical tetracaine, adrenaline, and cocaine (TAC) usually control the physical pain but have little or no effect on anxiety. Midazolam is a short-acting benzodiazepine with anxiolytic, hypnotic, and antegrade amnestic effects. In a double-blind, randomized clinical trial, we evaluated the efficacy of midazolam in alleviating anxiety during laceration repair in children less than 6 years old. On admission to the emergency department, anxiety level was determined on a scale of 1 to 4 based on a predetermined behavior criteria. Patients with high anxiety level (3 or 4) received a single oral dose of either midazolam (0.2 mg/kg) or placebo. The anxiolytic effect of midazolam was considered adequate if the anxiety level decreased two or more points (from 4 to less than or equal to 2 or from 3 to 1) during laceration repair. In the midazolam group (30), 70% of the children had a two-point or more decrease in anxiety level compared with 12% in the placebo group (25) (P less than .0001). No respiratory depression or other complications were noted in the midazolam group. We conclude that a single oral dose of midazolam (0.2 mg/kg) is a safe and effective treatment for alleviating anxiety in children less than 6 years old during laceration repair in the ED. PMID- 2203290 TI - Ketamine sedation for pediatric procedures: Part 2, Review and implications. AB - Ketamine produces rapid and consistent pediatric sedation with a predictable onset and recovery time. A wide margin of safety is afforded without the respiratory and cardiovascular depression commonly seen with alternative agents. The efficacy of ketamine is well established in anesthesia and dentistry and has extensive applications in other specialties. Ketamine sedation facilitates superior technical and cosmetic results while minimizing emotional trauma to distraught children. The much-feared complications of aspiration and laryngospasm are extremely rare when ketamine is used with proper precautions. Ketamine deserves increased use in the ED, and we advocate additional clinical investigation in this setting. PMID- 2203291 TI - Introduction to biostatistics: Part 5, Statistical inference techniques for hypothesis testing with nonparametric data. AB - Specific statistical tests are used when the null hypothesis (H0) is to be tested using nonparametric nominal or ordinal data. With nominal data, experimental results are expressed by proportions or frequencies. Chi-square or related tests (the Fisher's exact test or the rows by columns test) are appropriate for testing H0 with nominal data. Ordinal data permit arrangement of statistical results by rank. Rank-order tests used to test H0 with ordinal data include the Mann-Whitney U, Kolmogorov-Smirnov, Wilcoxon, Kruskal-Wallis, and Friedman tests. The Kruskal Wallis and Friedman tests permit multiple intergroup comparisons. Other rank order tests permit only single intergroup comparisons. Specific details to guide the researcher in the proper selection of these tests are presented. PMID- 2203292 TI - Chemotherapy for advanced thymoma. Preliminary results of an intergroup study. AB - OBJECTIVE: To determine the efficacy of combination therapy with cisplatin, doxorubicin, and cyclophosphamide alone or with radiotherapy for patients with extensive and those with limited unresectable thymoma. DESIGN: Nonrandomized, prospective phase I-II trial. SETTING: A Cooperative Oncology Group trial involving tertiary medical centers. PATIENTS: Twenty of twenty-two patients with measurable, extensive or limited, unresectable thymoma were evaluable for response. INTERVENTION: Patients were given cisplatin, 50 mg/m2 body surface area, doxorubicin, 50 mg/m2, and cyclophosphamide, 500 mg/m2, on day 1, with cycles repeated every 21 days until progression or until the maximally tolerated total doxorubicin dosage (for example, 450 mg/m2) was reached. Intravenous hydration with normal saline was administered during treatment courses. For responding patients with limited disease, 4500 cGy was administered to primary tumors after the second cycle of chemotherapy and before the initiation of the third cycle. MEASUREMENTS AND MAIN RESULTS: Three complete and eleven partial remissions were seen in 20 evaluable patients, for a total response rate of 70% (95% CI, 46% to 88%). The median duration of remission was 13 months with three patients remaining continuously disease free for over 2 years. The median survival time of all eligible patients was 59 months (CI, 22 months to infinity). Four patients developed infections, including listerial and aseptic meningitides, mucocutaneous candidiasis, and cryptococcal pneumonia, that were indicative of a defect in cell-mediated immunity. CONCLUSIONS: Combination therapy with cisplatin, doxorubicin, and cyclophosphamide frequently produces objective remissions in patients with advanced thymoma. Further experience with this treatment regimen is warranted to clarify potential prognostic factors in patients with unresectable thymoma. PMID- 2203293 TI - Chronic lymphocytic leukemia: new insights into biology and therapy. AB - PURPOSE: To review the recent advances in the biologic and clinical research of chronic lymphocytic leukemia. DATA IDENTIFICATION: English-language literature search using MEDLINE (1980 to 1990) and CANCERLIT (1980 to 1990), review of meeting abstracts and reports, and an extensive manual search of bibliographies of identified articles. STUDY SELECTION: Approximately 800 articles, abstracts, and book chapters were selected for analysis. DATA EXTRACTION: The literature was reviewed and 227 articles were selected as representative of the important advances in chronic lymphocytic leukemia. RESULTS OF DATA SYNTHESIS: Chronic lymphocytic leukemia is a disease of lymphocytes that appear to be mature but are biologically immature. These B lymphocytes arise from a subset of CD5-B cells that appear to have a role in autoimmunity. The pathogenesis of chronic lymphocytic leukemia is likely a multistep process, initially involving a polyclonal expansion of CD5-B cells followed by transformation of a single cell. Chromosome studies indicate that trisomy 12 is the most common abnormality, followed by 14q+, 13q, and 11q. These abnormalities portend a poor prognosis. Recent progress in the treatment of chronic lymphocytic leukemia involves three new drugs: fludarabine, pentostatin, and 2-chlorodeoxyadenosine. Recent preliminary results of allogeneic bone marrow transplantation present insights into the potential curability of chronic lymphocytic leukemia. Therapy with intravenous immunoglobulin can prevent or delay moderate bacterial infections in persons with chronic lymphocytic leukemia. CONCLUSION: Major advances in the biologic research of chronic lymphocytic leukemia have resulted in new understanding of this complex disease. New therapies, such as those with intravenous immunoglobulin and fludarabine, may lead to improved outcome. PMID- 2203294 TI - A new experimental approach for detecting emotional and motivational changes produced by neuroactive compounds in rodents. AB - A new potential approach for detecting subtle changes of emotional and motivational states in rodents is represented by the analysis of ultrasonic vocalizations emitted in a variety of situations. The ultrasonic calls differ somewhat in their physical characteristics depending on the species and on the situation. The results of our studies on the effects of various neuroactive substances on ultrasonic emissions during neonatal life and during sexual behaviour are briefly described here together with what is known of the biological function of the calls. PMID- 2203295 TI - Pathogenesis of age-related macular degeneration: embryologic concept. AB - Age-related macular degeneration (ARMD) is a bilateral progressive process which deprives millions of elderly individuals of central vision. Although numerous risk factors have been enumerated, embryonic implication, in relation to ARMD is an area that has been neglected to my knowledge. I address this new issue for the first time. PMID- 2203296 TI - Harada's disease associated with fibrous dysplasia. AB - Harada's disease is a well-described entity consisting of bilateral serous retinal detachments and diffuse choroiditis. The etiology of Harada's disease is obscure. Fibrous dysplasia of the orbit is also a well-known entity associated with many orbital and ophthalmologic findings. The defect in fibrous dysplasia appears to be a congenital nonhereditary abnormality in bone-forming mesenchyme. We present a case of Harada's disease and fibrous dysplasia of the orbit. The clinical photographs, fluorescein angiograms, ultrasound study, and histologic specimens are presented. PMID- 2203297 TI - Adenomyomatosis of the gall bladder: the NUH experience. AB - Adenomyomatosis (AD) is a degenerative disorder of the gall bladder wall which can be complicated by chronic inflammation and calculi. The true incidence of this disorder in South East Asians is not known. Nine Chinese patients with AD were discovered amongst 200 consecutive right upper quadrant ultrasound examinations. Four of them had cholecystectomy and were diagnosed as cholecystitis by the pathologist. Adenomyomatosis can be suspected on ultrasonography, but should be confirmed by oral cholecystography (OCG). There is great disparity in the ultrasound, OCG, surgical and histopathological diagnosis of this condition. This may be due to the fact that only complicated cases of AD come to surgery, where the presence of chronic cholecystitis or calculi detracts from recognising or overshadows the presence of AD. It is not known whether uncomplicated AD has any clinical significance and whether it, if given sufficient time, will lead to inflammation of the gall bladder. PMID- 2203298 TI - Benign retroperitoneal neurilemmoma--a case report. AB - Retroperitoneal neurilemmomas are the rarest of all retroperitoneal tumours. A rare case of a very large benign retroperitoneal neurilemmoma is presented. Pre operative diagnosis of these tumours is difficult and the majority are asymptomatic. They are usually detected as an abdominal mass on routine examination as in this case. Despite severe displacement and distortion of the inferior vena cava in this patient, there were no clinical abnormalities detected. The predominantly cystic nature of the tumour was well demonstrated by ultrasound and CT scan examination but the true nature of the tumour could not be diagnosed. It is very rare for these tumours to be malignant and recurrence after surgical excision is rare. PMID- 2203299 TI - An investigation into the age of cessation of endocranial growth using the techniques of logetronic copying and photosubtraction. AB - The classical teaching that endocranial growth is dependent on growth of the brain and thus should cease early in life has been questioned by Richardson and Blair who found marked expansive growth between 5 and 15 years in the occipital region. These authors were unable to comment on the age at which endocranial growth ceases because the changes towards the end of the growth period were of the same order of magnitude as the errors involved in digitizing standard cephalometric radiographs. In the present study, aimed at determining the age of cessation of endocranial growth, a very precise technique involving Logetronic copying and photosubtraction was used. Positive and negative Logetronic prints were made from standard 90 degree lateral cephalometric films of 28 normal boys taken at annual intervals between 5 and 15 years. The negative of one stage superimposed on the positive at the next stage revealed any growth changes by photosubtraction. Comparisons were made between films at 5 and 10 years, 10 and 13 years, 13 and 14 years and 14 and 15 years. All superimpositions and recordings were repeated by a second observer. All subjects showed growth changes between 5 and 10 years, 96% changed between 10 and 13 years, 64% changed between 13 and 14 years, and 54% showed growth changes between 14 and 15 years. Endocranial growth has ceased between 14 and 15 years in 46% of normal boys. PMID- 2203300 TI - Pharmacokinetics of FCE 22891, a new oral penem. AB - FCE 22891 is the oral prodrug of FCE 22101, a new broad-spectrum penem. The pharmacokinetics of FCE 22891 after single-dose administration, its absolute bioavailability, and the effect of food intake on its absorption were investigated in three different randomized crossover studies in healthy volunteers. Drug levels in blood and urine were measured by high-pressure liquid chromatography and bioassay. For optimal comparison of the results of all studies, and since there was good agreement of both methods, only the high pressure liquid chromatography results are included. The pharmacokinetics of the penem were linear, and its bioavailability after oral administration was 42 +/- 11%. Food intake increased the total area under the curve from 0 h to infinity from 11.9 +/- 3.5 to 14.1 +/- 2.4 mg.h/liter. A specific side effect, i.e., bladder complaints, was registered in some volunteers taking FCE 22891 at doses greater than or equal to 1.0 g. PMID- 2203301 TI - Investigation of potential interaction of ciprofloxacin with cyclosporine in bone marrow transplant recipients. AB - The effect of the 4-quinolone antimicrobial agent ciprofloxacin on the concentration in plasma and the pharmacokinetics of the immunosuppressive agent cyclosporine was studied in 10 bone marrow transplant recipients. There were no statistically or clinically significant changes in cyclosporine trough concentrations or areas under the concentration-time curve following oral doses of 500 mg of ciprofloxacin every 12 h for 4 days. The data suggest a lack of relevant pharmacokinetic interaction of ciprofloxacin with cyclosporine. There was no indication of an enhanced nephrotoxicity for this drug combination. PMID- 2203302 TI - Inhibition of Pneumocystis carinii dihydropteroate synthetase by sulfa drugs. AB - A new reversed-phase high-pressure liquid chromatography assay procedure for dihydropteroate synthetase (DHPS) that involves the elution of the enzyme incubation solution with a series of three solvents of decreasing polarity (ammonium phosphate buffer, 10% methanol, and 50% methanol) was designed. By this procedure DHPS was detected in Escherichia coli and Pneumocystis carinii with specific activities of 450 and 14 U/mg, respectively. A comparison of the effects of five sulfa drugs on P. carinii DHPS activity revealed that dapsone is the most potent of these drugs. PMID- 2203303 TI - Safety, tolerance, and pharmacokinetic evaluation of cefepime after administration of single intravenous doses. AB - In this double-blind, single-dose phase I study, the safety and tolerance of cefepime were assessed in 24 healthy male subjects, with ceftazidime as the control drug. Four subjects in each of the six dose groups (62.5, 125, 250, 500, 1,000, or 2,000 mg as a 30-min intravenous infusion) received each antibiotic, according to a crossover design, with a 2-day washout period between treatments. Blood and urine samples were obtained to characterize the pharmacokinetics of cefepime. Plasma and urine samples were assayed for intact cefepime. Samples containing ceftazidime were discarded. The adverse effects observed in the study were mild and infrequent, with prompt recovery from adverse experiences and abnormal laboratory values. The cefepime pharmacokinetic parameters for the therapeutically significant doses of 250 to 2,000 mg appeared to be proportional to dose and similar to literature values for ceftazidime. The elimination half life of about 2 h was independent of the dose. Urinary recovery of intact cefepime was invariant with respect to dose; an overall mean value of 82% of dose was obtained for the four highest levels. Mean renal clearance was 105 ml/min and suggestive of glomerular filtration as the primary excretion mechanism. In normal humans, the safety and pharmacokinetic profiles of cefepime are very similar to those of ceftazidime. PMID- 2203304 TI - Interactions of ceftazidime and tobramycin in patients with normal and impaired renal function. AB - We studied the in vivo interaction of ceftazidime and tobramycin in normal volunteers and anuric patients given each drug separately or both drugs in combination. Kinetic analysis of plasma concentration data showed minor changes in the disposition of these agents when they were given concurrently. However, the resulting clearance of both tobramycin and ceftazidime was unchanged when these drugs were given concurrently. The volume of distribution of tobramycin at steady state was increased by 20% in normal volunteers when given with ceftazidime. The increase in distribution was accompanied by a slight decrease in ceftazidime elimination rate. No additional alteration in dosing over those necessary to adjust for a decrease in renal function is necessary when giving this combination. PMID- 2203305 TI - Apparent biliary pseudolithiasis during ceftriaxone therapy. AB - Biliary pseudolithiasis has been reported in patients who received ceftriaxone therapy. To examine this phenomenon further, serial gallbladder sonograms were evaluated in 44 adult patients who received intravenous ceftriaxone at 2 g or a placebo daily for 14 days in a double-blind controlled study. Ultrasound examinations of gallbladders were performed on days 1 and 14 of therapy and 2 weeks posttherapy if abnormalities were observed on day 14. Eight patients were unevaluable because of abnormal base-line gallbladder sonograms. Thirty-six patients (ceftriaxone, n = 28; placebo, n = 8) demonstrated normal baseline gallbladder sonograms and were evaluated for the development of change. A total of 6 of 28 (21.4%) ceftriaxone-treated patients and 1 of 8 (12.5%) patients who received the placebo demonstrated abnormal gallbladder sonograms on day 14 (P = 0.491). Four of the six ceftriaxone-treated patients demonstrating abnormal sonograms were clinically asymptomatic, while two patients reported vomiting. The abnormal sonograms of gallbladders of patients treated with ceftriaxone returned to normal between 9 and 26 days posttherapy. These data suggest an association between ceftriaxone treatment and the development of gallbladder abnormalities on ultrasound examination which resolve spontaneously on discontinuation of ceftriaxone therapy. PMID- 2203306 TI - Failure of ceftazidime-amikacin therapy for bacteremia and meningitis due to Klebsiella pneumoniae producing an extended-spectrum beta-lactamase. AB - A multiple trauma patient failed treatment with ceftazidime and amikacin for bacteremia and meningitis due to a Klebsiella pneumoniae strain that produced a novel, plasmid-mediated beta-lactamase. Both pre- and posttreatment isolates were resistant to ceftazidime (MIC, greater than or equal to 64 micrograms/ml) and various penicillins but not to other expanded-spectrum cephalosporins. The beta lactamase had a pI of 5.25 and was encoded on a conjugal plasmid of approximately 150 kilobases. DNA hybridization studies indicated that the enzyme was a TEM derivative. PMID- 2203307 TI - Molecular biology of penicillin and cephalosporin biosynthesis. PMID- 2203308 TI - Intracellular activity of tosufloxacin (T-3262) against Salmonella enteritidis and ability to penetrate into tissue culture cells of human origin. AB - The intracellular antimicrobial activity of tosulfoxacin was tested against Salmonella enteritidis C-32 by using human lung fibroid WI-38 cells and was compared with those of ofloxacin and norfloxacin. The intracellular antimicrobial activities of these drugs were evaluated by determining the numbers of viable organisms remaining within cells after treatment with various drug concentrations. At 0.2 and 0.78 microgram/ml, tosufloxacin suppressed intracellular multiplication of S. enteritidis C-32 more effectively than ofloxacin and norfloxacin did. The ability of tosufloxacin to penetrate into WI 38 cells was also determined by the velocity gradient method. The ratio of the intracellular concentration to the extracellular concentration of tosufloxacin was 1.7- and 2.6-fold higher than those of ofloxacin and norfloxacin, respectively. The results indicate that the potent intracellular bactericidal activity of tosufloxacin may be due not only to its high in vitro activity but also to its ability to penetrate into cells at a high level. PMID- 2203309 TI - Open trial of cefepime (BMY 28142) for infections in hospitalized patients. AB - The safety and efficacy of cefepime, a new broad-spectrum, semisynthetic parenteral cephem antibiotic, were evaluated in an open trial at a single hospital. Seventy patients were treated with cefepime: 44 had lower respiratory tract infections, 4 had urinary tract infections, and 22 had skin or soft tissue infections. Of 65 clinically evaluable patients, 64 (98%) had satisfactory responses. No mortality or superinfections occurred. Of 57 respiratory and urinary tract pathogens, 54 (95%) were eradicated and 3 (5%) persisted after therapy. Five bacteremias (two with Streptococcus pneumoniae and one each with Staphylococcus aureus, Proteus mirabilis, and a coagulase-negative staphylococcus) were eradicated. MICs ranged from 1 to 8 micrograms/ml for 13 S. aureus and 9 Pseudomonas aeruginosa isolates and were less than or equal to 0.125 micrograms/ml for 10 streptococcal isolates. Adverse effects occurred in two patients: transient diarrhea and Clostridium difficile toxin in the stool in one patient and loose bowel movements and increased transaminases in the other patient. Cefepime appeared to be well tolerated in humans and was effective against a wide range of isolates, including S. aureus and P. aeruginosa. PMID- 2203310 TI - In vivo efficacy of SM-8668 (Sch 39304), a new oral triazole antifungal agent. AB - SM-8668 (Sch 39304) is a new oral antifungal agent which we evaluated in comparison with fluconazole in various fungal infection models. The prophylactic effect of SM-8668 was excellent against systemic candidiasis, aspergillosis, and cryptococcosis in mice. The 50% effective dose for SM-8668 was assessed at 10 days after infection and was 0.18, 3.7, and 5.9 mg/kg (body weight), respectively, for the above-mentioned fungal diseases. Fluconazole was about four times less effective than SM-8668 against systemic candidiasis and was only slightly effective at doses of 80 and 25 mg/kg against systemic aspergilosis and cryptococcosis, respectively. SM-8668 was also about four to eight times more active than fluconazole against vaginal candidiasis in rats and against dermatophytic infection in guinea pigs. In addition, topical SM-8668 was as effective as topical miconazole or tioconazole against skin mycosis in guinea pigs. After oral administration, SM-8668 showed a maximum concentration in serum similar to that of fluconazole in both mice and rats, but the elimination half life and area under the serum concentration-time curve for SM-8668 were twice those for fluconazole. PMID- 2203311 TI - High-level chromosomal gentamicin resistance in Streptococcus agalactiae (group B). AB - This is the first report of high-level gentamicin resistance in a group B streptococcus. Strain B128 of serotype II was isolated from an infected leg wound in 1987. B128 was resistant to high levels of gentamicin as well as of all other available aminoglycosides and was also resistant to tetracyclines. No bactericidal synergism was found between ampicillin or vancomycin and any of these aminoglycosides. Gentamicin, kanamycin, streptomycin, and tetracycline resistance determinants transferred by conjugation into a plasmid-free group B streptococcus recipient at a frequency of 10(-8) to 10(-9) transconjugants per donor cell. No transconjugants were detected when streptococci of groups A, C, and G, Streptococcus sanguis, or Enterococcus faecalis was used as a recipient. No plasmids were detected in B128 or in any of the four transconjugants tested. By DNA-DNA hybridization, homology was detected between gene aac6/aph2, of E. faecalis origin, and a 2.4-kilobase HindIII chromosomal fragment of B128; homology to the genes aph3 and aadE, of E. faecalis origin, was found with HindIII chromosomal fragments of the same size (3.0 kilobases). Strains like B128, which potentially can be responsible for severe neonatal infections, are of great clinical concern, since there are to date no antibiotic combinations exhibiting bactericidal synergism against them. PMID- 2203312 TI - In vivo effects of fenpropimorph on the yeast Saccharomyces cerevisiae and determination of the molecular basis of the antifungal property. AB - The effects of fenpropimorph on sterol biosynthesis and growth of Saccharomyces cerevisiae were examined to pinpoint the mode of action of fungicides that inhibit ergosterol biosynthesis. Taking advantage of sterol auxotrophy and sterol permeability in mutant strains, we show that growth inhibition is strongly correlated with inhibition of sterol biosynthesis. We confirm that in vivo and at low concentrations, fenpropimorph inhibits delta 8----delta 7-sterol isomerase, and in addition, when it is used at higher concentrations, it inhibits delta 14 sterol reductase. We show also that the fungistatic effect of fenpropimorph is not due to the accumulation of abnormal sterols in treated cells but is linked to the specific inhibition of ergosterol biosynthesis, leading to the arrest of cell proliferation in the unbudded G1 phase of the cell cycle. PMID- 2203313 TI - In vitro activity of LJC10,627, a new carbapenem antibiotic with high stability to dehydropeptidase I. AB - The in vitro activity of LJC10,627, a new carbapenem, was compared with those of imipenem and ceftazidime. LJC10,627 had broad-spectrum activity against gram positive and gram-negative clinical isolates. The MICs of this compound for 90% of members of the family Enterobacteriaceae tested (MIC90s), including strains resistant to ceftazidime, ranged from 0.1 to 25 micrograms/ml. LJC10,627 inhibited Pseudomonas aeruginosa at an MIC90 of 3.13 micrograms/ml; it thus was twofold more active than imipenem. This compound inhibited Haemophilus, Neisseria, and Branhamella species at MIC90s of 3.13, 0.1, and 0.1 micrograms/ml, respectively. LJC10,627 was two- to fourfold less active than imipenem against methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis at MIC90s of 0.1 and 0.39 microgram/ml. However, the compound was found to be twofold more active than imipenem against Bacteroides fragilis at an MIC90 of 1.56 microgram/ml. LJC10,627 was very stable to various beta-lactamases except for Xanthomonas maltophilia oxyiminocephalosporinase type II. LJC10,627 was minimally hydrolyzed by swine renal dehydropeptidase I; its residual activity was 93.0% after 2 h. Killing kinetics of this compound for Escherichia coli and Pseudomonas aeruginosa showed that bactericidal action occurred at concentrations above the MIC (0.05 and 0.39 microgram/ml, respectively). LJC10,627 had a high affinity for penicillin-binding proteins 2, 4, and 1B(s) of Escherichia coli and Pseudomonas aeruginosa and penicillin-binding proteins 1 and 4 of Staphylococcus aureus. PMID- 2203314 TI - Increased susceptibility of ribulose-1,5-bisphosphate carboxylase/oxygenase to proteolytic degradation caused by oxidative treatments. AB - The susceptibility of the chloroplastic enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase to proteolysis by trypsin, chymotrypsin, proteinase K, and papain is enhanced by oxidative treatments including spontaneous oxidation of cysteines. Proteinases exhibit a high specificity for the oxidized inactive form of the carboxylase, cleaving its large subunit. Treatment of the inactive enzyme with dithiothreitol results in partial recovery of both carboxylase activity and resistance to proteolysis. This behavior may explain the specific degradation of ribulose-1,5-bisphosphate carboxylase/oxygenase that occurs in vivo during leaf senescence. PMID- 2203315 TI - [Photodynamic therapy in the early treatment of cancer]. AB - The clinical application of photodynamic therapy (PDT) began in the late 1970's. Hematoporphyrin derivative has been used as a photosensitizer and recently Photofrin II (Dihematoporphyrin ether, DHE) was also developed as a second generation photosensitizer. The argon dye laseris used to excite the photosensitizer, however an eximer dye laser was recently developed as more effective laser. In a multicenter research study project team (7 institutions) on photodynamic therapy organized by the Ministry of Health and Welfare, 133 cases of gastric cancer (including 120 cases of early stage cancer), 209 cases of lung cancer (69 cases of early stage cancer), 66 cases of esophageal cancer (22 cases of early stage cancer), 68 cases of bladder cancer (68 cases of early stage cancer), and 86 cases of other organ cancers were treated. In early stage cancer cases 77.3% showed complete remission (CR) but among those the recurrence was 15.7% in lung cancer cases and opposed to 100% CR and 22.2% recurrence in gastric cancer cases, 80% CR and no recurrence in esophageal cancer cases, and 68.6% CR and 58.3% recurrence in bladder cancer cases. Especially in limited lesions less than 1 cm in diameter, the CR was obtained in 100% and the recurrence was recognized in only 1 (2.6%) of 28 lung cancer lesions, 100% CR and no recurrence was obtained in 30 lesions of gastric cancer and also 100% CR with no recurrence was recognized in 16 lesions in bladder cancer. This study suggests that PDT has the potential to cure early stage cancer lesions. PMID- 2203316 TI - [Treatment of advanced ovarian cancer]. AB - Significant prolongation of survival time has been brought by cisplatin containing regimen, but no significant improvement of 5 year survival rate has been achieved. Concerning to four clinical problems we face to now, my opinion was described as follows. 1) Importance of chemotherapy in the treatment of advanced ovarian cancer: The most important factor for the cure of advanced ovarian cancer is the efficacy of the regimen used. 2) Regimen and number of cycles needed: Cisplatin and carboplatin are dose-dependent drugs and we should make effort to make dose up as much as possible. May be 6 cycles will be suitable number of administration. 3) Postoperative chemotherapy or preoperative chemotherapy (Neo-adjuvant)?: Serous adenocarcinoma is observed with high frequency around 70% and the efficacy rate of cisplatin containing regimen is exceeded more than 80%. Neo-adjuvant chemotherapy should be tried in advanced ovarian cancer. 4) Second line chemotherapy: At present, no effective drug is available for the treatment of true cisplatin refractory cancer. Therefore we should perform aggressive surgery and severe chemotherapy at the first time of treatment. By combination of surgery and chemotherapy, at least clinical CR (Complete resection or complete response) is indispensable for achieving significant improvement of 5 year survival rate, In this meaning, chemotherapeutic CR is necessary in postoperative chemotherapy and surgical CR is required in Neo-adjuvant chemotherapy. PMID- 2203317 TI - [Relapsed stage I neuroblastoma successfully treated by allogeneic bone marrow transplantation in second remission: case report of a 7-year-old girl]. AB - Stage I neuroblastoma in a seven-year-girl have had local recurrence with bone metastasis. Second surgery was performed after the aggressive chemotherapy including cisplatin, VP16, cyclophosphamide, vincristine and doxorubicin. She underwent allogeneic bone marrow transplantation from her HLA identical brother, following the preparative regimen consisting of high-dose melphalan and total body irradiation (12 Gy). Clinical course after the transplantation was uneventful. She is still alive with no evidence of disease for twenty-eight months after the transplantation. It is suggested that bone marrow transplantation is an effective way of therapy even in a patient with relapsed neuroblastoma. PMID- 2203318 TI - [Development of carboplatin]. AB - Carboplatin (CBDCA; commercial name: Paraplatin) is a platinum complex having 1 cyclobutanedicarboxylic acid group at the two chlorine positions of cisplatin (CDDP). In the preclinical studies, CBDCA was proved to be almost equally effective to various murine tumors compared to cisplatin. Compared to cisplatin, of which free platinum was not detected from 2 hr after administration, the free type of more than 85% of total platinum concentration remained in the blood even 8 hrs after administration. Total urine excretion at 2-4 hrs after administration of CBDCA was about 57-82%, indicating CBDCA's relative rapid urine excretion compared to CDDP. In the clinical trials in Japan, appreciable clinical responses were observed in head and neck, small cell lung, ovarian, uterine cervical cancers, testicular tumor and malignant lymphoma. The renal toxicity was considerably slight, resulting in almost no hydration during treatment. Nausea and vomiting were also slight and there were no hearing-loss and neurotoxicities. The dose-limiting factor (DLF) in the phase I study was myelosuppression. From these results, it was found that carboplatin's antitumor efficacies were almost identical with cisplatin and much less toxic than cisplatin. Carboplatin will serve as a useful antitumor drug in current cancer chemotherapy. PMID- 2203319 TI - Lupus-associated protein-losing enteropathy. AB - Fourteen cases of primary lupus-associated protein-losing enteropathy have now been reported in the English-language literature. These cases were reviewed to find any consistent pattern of presentation. Lupus-associated protein-losing enteropathy typically occurs in young women, and is characterized by the onset of profound edema and hypoalbuminemia. In many cases it is the first obvious manifestations of systemic lupus erythematosus. Diarrhea is present about 50% of the time, but steatorrhea is absent. Diagnosis of protein-losing enteropathy can be successfully made by radioisotopic studies or 24-hour stool alpha 1 antitrypsin clearance. A normal lymphocyte count, elevated serum cholesterol, and absence of lymphangiectasia on intestinal biopsy help distinguish lupus associated protein-losing enteropathy from protein-losing enteropathies due to direct or indirect lymphatic obstruction. Normal endoscopy and mucosal biopsy can rule out protein loss due to mucosal disruption. Prognosis appears to be excellent with corticosteroids, although other immunosuppressive therapies have been successfully used. A typical and illustrative case is presented as a focal point for review and discussion. PMID- 2203320 TI - Practice guidelines: a new reality in medicine. I. Recent developments. AB - There is growing interest in the use of practice guidelines for physicians as a means of reducing inappropriate care, controlling geographic variations in practice patterns, and making more effective use of health care resources. Recent developments at the national health policy level suggest that practice guidelines will play an increasingly prominent role in the practice of medicine. The federal government has created a new US Public Health Service agency with responsibility for practice guidelines. Guidelines have been developed by more than 35 physician organizations and specialty societies. The American Medical Association and the Council of Medical Specialty Societies have endorsed practice guidelines and are organizing specialty societies to set policy on the subject. Academic medical centers have formed a research consortium on practice guidelines. Independent research centers (eg, the RAND Corporation and the Institute of Medicine) are developing methods for assessing appropriateness and setting guidelines. Other groups, such as hospitals, insurers, managed care plans, and private enterprises, are also directly involved. The implications of these developments are far reaching. PMID- 2203321 TI - Steroids for Pneumocystis carinii pneumonia and respiratory failure in the acquired immunodeficiency syndrome. A reassessment. AB - Patients with acquired immunodeficiency syndrome who have Pneumocystis carinii pneumonia (PCP) and respiratory failure have a high mortality. Previous reports have suggested that corticosteroids administered in conjunction with antibiotics improve the outcome in these patients. We reviewed our experience with adjunctive corticosteroids in 20 patients with acquired immunodeficiency syndrome and respiratory failure due to PCP to determine if this was the case. Fourteen patients responded to therapy with initial reversal of their respiratory failure. However, nine of these relapsed with recurrence of respiratory failure after steroid therapy was withdrawn. Eight (40%) of the patients remained alive and well 3 months or more following treatment. When the analysis was restricted to patients requiring intubation, only 25% were alive 3 months later. Despite good initial response to steroids in PCP and respiratory failure, survival remains limited. Controlled trials are needed to define better the role of steroid treatment in these patients. PMID- 2203322 TI - Comparison of psyllium hydrophilic mucilloid and cellulose as adjuncts to a prudent diet in the treatment of mild to moderate hypercholesterolemia. AB - The effects of the administration of 5.1 g of psyllium or placebo (cellulose) twice daily for 16 weeks were compared as adjuncts to a prudent diet in the management of moderate hypercholesterolemia in a parallel, double-blind study. Psyllium decreased the total cholesterol level by 5.6% and the low-density lipoprotein cholesterol level by 8.6%, whereas the levels were unchanged in the placebo group. The high-density lipoprotein cholesterol level decreased during the diet stabilization period in both groups and returned to near-baseline values by week 16. Plasma triglyceride levels did not change substantially in either group. Subject compliance to treatment was greater than 95%. These data suggest that psyllium hydrophilic mucilloid in a twice-daily regimen may be a useful and safe adjunct to a prudent diet in the treatment of moderate hypercholesterolemia. PMID- 2203323 TI - The optimum use of needle aspiration in the bacteriologic diagnosis of cellulitis in adults. AB - Twenty-five adult inpatients with cellulitis were prospectively studied to determine if distinctive predisposing factors, characteristic clinical findings, or specific laboratory features were predictive of isolating a pathogen from needle aspiration cultures of the leading edges of their lesions. In the univariate analysis, age, underlying disease, temperature, and white blood cell count at admission to the hospital correlated with a positive needle aspiration culture. A series of logistic regressions were performed to determine if each of these variables was independently associated with a positive needle aspiration culture. The final model demonstrated that underlying disease and body temperature were independent predictors of obtaining a positive needle aspiration culture. Consequently, the addition of white blood cell count and age failed to enhance the model's predictability. For most patients this procedure will not be helpful [corrected] in establishing a bacteriologic diagnosis. On the basis of these results, the needle aspiration technique will most likely yield pathogens in patients with underlying disease that predisposes to the acquisition of cellulitis. These patients may also fail to mount a febrile response to infection. PMID- 2203324 TI - The role of skin testing for penicillin allergy. AB - Skin testing for penicillin allergy is an imperfect predictor of severe allergic reactions. We used decision analysis to identify the types of allergy history for which skin testing should alter management. The treatment threshold, the probability of a serious allergic reaction at which point one should switch from penicillin to another antibiotic, depends on the quality of life associated with the clinical outcomes. We measured 12 physicians' attitudes toward the outcomes of treatment with penicillin or vancomycin for Streptococcus viridans endocarditis in patients with a history of penicillin allergy. The clinicians' threshold probabilities ranged from .00010 to .00210 (median, .00013). Given the sensitivity (89% to 96%) and specificity (89% to 96%) of skin testing and our clinicians' median threshold, test results could alter the choice of antibiotic when the probability of a severe allergic reaction is between .00001 and .001. This range corresponds to a weak history of penicillin allergy. Although the decision should be individualized, our study suggests that skin testing is unnecessary when the patient has a convincing history of a severe allergic reaction to penicillin. PMID- 2203325 TI - [The "biparietal rejection syndrome" versus "environmental dependency syndrome" and Kluver-Bucy syndrome]. PMID- 2203326 TI - [Melanotic medulloblastoma. Ultrastructural and histochemical study of a case]. AB - A electron microscopic and immunohistochemical study of a Melanotic medulloblastoma is reported. The cerebellar tumor was located in the vermis of a 6-year-old boy, dead 11 months after diagnosis. The tumor consisted of medulloblastoma-like areas with focal differentiation and pseudoepithelial structures pigmented with melanin. Electron microscopy showed melanosomes and tight junctions in pigmented areas. On immunohistochemistry, the cytoplasm of melanotic cells were positive to S-100 protein and the differentiated glial cells to GFAP. The tumor histogenesis, its relationship with other pigmented tumors of the CNS and their low frequency is commented on. PMID- 2203327 TI - Prolactin and cortisol responses to MK-212, a serotonin agonist, in obsessive compulsive disorder. AB - To examine further the serotoninergic system in obsessive-compulsive disorder (OCD), the plasma concentrations of cortisol and prolactin and the behavioral responses after oral administration of MK-212 (6-chloro-2-[1-piperazinyl] pyrazine), a serotonin agonist, and placebo were studied in 17 patients with OCD and nine normal controls. The two groups did not differ significantly in basal plasma prolactin or cortisol levels. Nevertheless, both the prolactin and cortisol response to oral administration of MK-212 (20 mg) were significantly blunted in the patients with OCD compared with those of the normal controls. MK 212 did not affect the intensity of OCD symptoms. However, MK-212, as compared with placebo, produced slight but statistically significant increases in self ratings of nausea, dizziness, anxiety, feeling strange, and mixed feelings of calmness and restlessness, as well as depression and feeling high. These behavioral ratings were not significantly different in patients and normal controls. These findings are consistent with previous reports of diminished serotoninergic responsivity in OCD and raise the possibility of subsensitivity of at least some serotonin receptors in this disorder. PMID- 2203328 TI - [Mechanism of the response of the living body to foreign material]. PMID- 2203329 TI - Acid etching of a glass ionomer cement base: SEM study. AB - The effects of acid-etching duration on the surface of a glass ionomer cement designed for use as an intermediary layer between composite resin and dentine were investigated. Cement topography changes occurred which could be related to etch duration. When compared with enamel etched for a similar period, undue loss of cement substance was not observed for any of the etch times used. PMID- 2203330 TI - An electron microscopic evaluation of the enamel surface subsequent to various debonding procedures. AB - In this study, enamel surface roughness was investigated following the use of various combinations of bonding agents, burrs and polishing procedures. Orthodontic brackets were bonded to 135 premolar teeth extracted from adolescents. Subsequent to debonding and finishing, the enamel surface was gold coated and examined in the scanning electron microscope. Each 200x photomicrograph was graded according to surface roughness and assigned to one of four selected standard grades. The use of different composites and different burs showed no significant effect on the finish of the enamel surface using Chi-square tests. Only two finishing procedures had a significant effect on surface roughness. The use of a Soflex disc followed by pumice slurry resulted in the roughest enamel surface and the use of pumice alone produced the smoothest enamel surface. PMID- 2203331 TI - Factor XI deficiency disclosed following haemorrhage related to a dental extraction. Brief review and case report. AB - Factor XI deficiency is a relatively common hereditary coagulation disorder manifested generally as diffuse oozing from a surgical site. Dentists may be the first to discover this deficiency and other coagulopathies after simple tooth extraction. A case is reported which illustrates a typical presentation of this disorder. The need for haematological examination and special dental care is discussed. PMID- 2203332 TI - Bruxism: a review of the literature. Part I. AB - A review of the literature on bruxism--a condition which has been clinically recognized since the late nineteenth century--is presented. It will be seen that there is not complete agreement on the definition of this activity, and its aetiology and treatment remain controversial. PMID- 2203333 TI - Interpersonal processes in dentistry. Part II. AB - This paper relates an investigation of dentists' perceptions of their patients to a literature review of the interpersonal processes involved in professional helping. Although the concerns of dentists were markedly similar to those of other helping professionals there was a difference in priority possibly reflecting situational factors. The priority of the dentists' concerns were patient likeability, manageability and prognosis. It has been found that, for other helping professionals, four person-perception processes that occur in everyday life often lead to unfavourable perceptions of clients and work against the motivation to help them. Significant evidence of three of these four processes was found in the constructs described by the dentists. The three processes were: (a) attraction to similarity, (b) personalistic tendency in attributions, and (c) perceptual consequences of the patient's resistance to influence. The fourth process, a tendency to sample negative aspects of patients' behaviour, was not in evidence; on the contrary there was a significant tendency to sample positive aspects of the patients' behaviour by this sample of dentists. PMID- 2203334 TI - Positive immunostaining of ovine congenital progressive muscular dystrophy with antibody against N- and C-terminal dystrophin. PMID- 2203335 TI - The functional importance of multiple actin isoforms. AB - Actin is a protein that plays an important role in cell structure, cell motility, and the generation of contractile force in both muscle and nonmuscle cells. In many organisms, multiple forms of actin, or isoactins, are found. These are products of different genes and have different, although very similar, amino acid sequences. Furthermore, these isoactins are expressed in a tissue specific fashion that is conserved across species, suggesting that their presence is functionally important and their behavior can be distinguished quantitatively from one another in vitro. In muscle cells, they are differentially distributed within the cell and some are specifically associated with structures such as costameres, mitochondria, and neuromuscular junctions. There is also good evidence for specific isoactin function in microvascular pericytes and in the intestinal brush border. However, the necessity of specific isoactins for various functions has not yet been conclusively demonstrated. PMID- 2203336 TI - Expression of human plasma protein genes in ageing transgenic mice. AB - Introduction of human plasma protein genes into the mouse genome to produce transgenic mice furnishes an in vivo model for correlating chromosomal DNA sequences with developmental and tissue-specific expression. The liver produces an array of plasma proteins that circulate throughout the body contributing to homeostasis. Non-hepatic tissue sites of synthesis have been identified where a local provision of plasma proteins is needed. Analysis of expression of human plasma protein genes in ageing transgenic mice appears especially promising in identifying DNA sequences that respond to environmental adversities such as inflammatory factors, hormonal changes and metal toxicity. The results indicate that human genes encoding and controlling liver plasma proteins serve as useful models for studying genetic regulation in the background of development and ageing. PMID- 2203337 TI - Inherited disorders of vitamin B12 utilization. AB - Inborn errors of vitamin B12 (cobalamin) metabolism are associated with homocystinuria and methylmalonic aciduria, either alone or in combination. A number of these disorders have provided the first evidence for the existence of important steps in the transport or metabolism of cobalamin in eukaryotic cells. Eight complementation classes have been defined on the basis of somatic cell hybridization studies. Although the majority of patients present in infancy or early childhood, some are not diagnosed until adolescence or later. For some of these disorders, prenatal diagnosis and therapy with cobalamin during pregnancy has been attempted. Although only males have been described with cblE disease, all of these disorders are presumed to be autosomal recessive in inheritance. The clinical and laboratory aspects of the different complementation classes (cblA cblG) are reviewed here. PMID- 2203338 TI - Conservation of RNA polymerase. PMID- 2203339 TI - Multistep emancipation of tumors from growth control: can it be curbed in a single step? PMID- 2203340 TI - Virus reconstitution and the proof of the existence of genomic RNA. PMID- 2203341 TI - Sialyltransferase activities in cultured rat hepatocytes. AB - Previous studies on the age and sex dependency of the ganglioside patterns in rat liver in vivo and the concomitant determination of the activities of some enzymes involved in these pathways revealed the prominent role of the sialylation of GM3 to GD3 in determining the flow to the mono (a)- and polysialo (b)-series, respectively. Here, the influence of hormones on the activities of GM3 and GD3 synthases in isolated hepatocytes was studied. The combination of several factors (insulin, glucagon, epidermal growth factor, glucocorticoids) was found to be necessary for maintaining in vivo activity levels of GD3- but not of GM3 synthase. PMID- 2203342 TI - In vivo expression of rat liver c-erbA beta thyroid hormone receptor in yeast (Saccharomyces cerevisiae). AB - To study thyroid hormone receptor (TR), we developed an in vivo expression system in yeast by using a copper-responsive yeast metallothionein promoter and ubiquitin-fusion protein technology. The cDNA encoding full-length rat liver TR beta was expressed under the control of copper. The [125I]T3 binding activities to yeast extracts were significantly correlated with the added copper sulfate into the medium. Partially purified TR from the transformed yeast had a high hormone binding affinity (Kd = 0.34) for T3 and could bind thyroid hormone response element in gel retardation analysis. PMID- 2203343 TI - Bioluminescent immunoassay using a fusion protein of protein A and the photoprotein aequorin. AB - Aequorin is a photoprotein that emits light in the presence of Ca2+ ions. To develop a bioluminescent immunoassay based on the light emission property of aequorin, we have expressed the apoaequorin fusion protein with S. aureus protein A in E. coli by recombinant DNA techniques. The fusion protein expressed was purified by IgG-Sepharose affinity chromatography, gel filtration and HPLC procedures. The purified protein A-apoaequorin fusion protein has both the luminescent activity of aequorin and the IgG-binding ability of protein A. We compared results obtained using the protein A-aequorin fusion protein with those obtained using a protein A conjugated horseradish peroxidase based immunoassay, and found them to yield similar results. PMID- 2203344 TI - Increased glucose transporter (GLUT4) protein expression in hyperthyroidism. AB - We have studied skeletal muscle glucose uptake by perfused hindquarter preparations from rats treated with thyroxine. Basal glucose uptake (in the absence of insulin) was approximately 2 fold higher in muscle of hyperthyroid rats compared to controls. Insulin (10(-7) M) stimulated glucose uptake 4.0 and 6.8 fold in the 10 day and 30 day controls rats, respectively. Maximal glucose uptake (10(-7) M insulin) was not different in control and hyperthyroid rats and thus insulin responsiveness in the hyperthyroid animals was reduced to 2.5 fold stimulation. The abundance of the insulin-sensitive glucose transporter protein (muscle/fat, GLUT-4), measured by Western blot analysis using polyclonal antisera, was higher in skeletal muscle from both groups of hyperthyroid rats. These studies indicate that thyroid hormones increase basal glucose uptake in skeletal muscle and this is due, at least in part, to an increment of GLUT-4 isoform. Increased expression of muscle glucose transporter proteins may be responsible for the increased peripheral glucose utilization seen in hyperthyroidism. PMID- 2203345 TI - Microfilaments regulate the rate of exocytosis in rat basophilic leukemia cells. AB - Disruption of microfilaments in rat basophilic leukemia (RBL) cells by exposure to cytochalasin B is observed to potentiate the rate of antigen-stimulated secretion from these cells. Under these conditions, cytochalasin B is without effect on the antigen-stimulated production of inositol phosphates or 45Ca2(+) influx. In streptolysin-O-permeabilized RBL cells, cytochalasin B is observed to potentiate the rate of secretion in response both to guanosine 5'-(2-thio)-O triphosphate (GTP gamma S) and to Ca2+ (buffered between 0.1 and 10 microM). However, under these conditions, cytochalasin B does not affect to antigen stimulated production of inositol phosphates. Consistent with these data, microfilaments are proposed to regulate a terminal step in exocytosis, in a physiologically relevant manner. PMID- 2203346 TI - Tissue-specific expression of rat pyruvate kinase L/chloramphenicol acetyltransferase fusion gene in transgenic mice and its regulation by diet and insulin. AB - We produced transgenic mice carrying about 3 kb of the 5'-flanking sequence of the rat pyruvate kinase L gene linked to the chloramphenicol acetyltransferase (CAT) structural gene. Expression of the transgene was observed only in tissues in which the endogenous L-type pyruvate kinase is expressed. Dietary glucose or insulin induced similar increases in the levels of CAT and L-type pyruvate kinase mRNAs in the liver. However, the fructose-induced level of CAT mRNA was about 3- and 6- fold lower than those of endogenous L-type pyruvate kinase mRNA in the liver and kidney, respectively, confirming our previous finding that stabilization of the transcripts of the pyruvate kinase L gene is an important regulatory step in fructose induction, especially in the kidney. Thus we conclude that all the cis-acting elements responsible for tissue-specific expression of the L-type pyruvate kinase and its stimulation by dietary components and insulin are localized in the sequence from about nucleotide -3000 to +37 in the pyruvate kinase L gene. PMID- 2203347 TI - The effect of extracellular calcium on the contractile action of endothelin. AB - The tension developed by rat aortic strips in response to endothelin-1 is determined by three types of mechanisms: a [Ca2+]o independent mechanism, L-type Ca2+ channels and a [Ca2+]o dependent, verapamil insensitive, mechanism. Their relative contributions to the tension recorded 30 minutes after the addition of 50 nM endothelin-1 were 43%, 34% and 23%. Upon longer exposures to endothelin-1, the whole tension could be abolished by reducing [Ca2+]o to 20 nM. Endothelin-1 induced contractions were highly sensitive to changes in free [Ca2+]o. The EC50 value for the [Ca2+]o dependence of endothelin-1 induced contractions was 600 nM, a value 400 times lower than the corresponding value found for KCl induced contractions (250 microM). These results suggest that extracellular Ca2+ is necessary for full tension development in response to endothelin-1 but that a major action of endothelin-1 is to increase the sensitivity of pharmacomechanical coupling mechanisms to Ca2+. PMID- 2203348 TI - The purification and characterization of recombinant human renin expressed in the human kidney cell line 293. AB - The cDNA encoding human preprorenin has been introduced into the adenovirus transformed human kidney cell line 293. The recombinant 293 cells expressed and secreted prorenin; trypsin was used to activate the secreted prorenin to renin in vitro. The recombinant protein was purified to homogeneity by a single affinity chromatographic step. Using synthetic tetradecapeptide, the Km was 57.1 +/- 9.3 microM and the kcat was (7.48 +/- 1.57) x 10(3)/hr. Activation with trypsin resulted in a secondary cleavage between Arg53 and Leu54 generating a two chain form held together via a disulfide between Cys51 and Cys58. This secondary cleavage did not affect enzyme activity as determined by the ability of renin to degrade a synthetic tetradecapeptide substrate. Our paper demonstrates the potential for producing large quantities of renin from human kidney cells and also suggests that the use of trypsin, which has been widely used to convert prorenin to renin in vitro, causes a secondary cleavage in the renin peptide chain. PMID- 2203349 TI - Hydrolysis of synthetic chromogenic substrates by HIV-1 and HIV-2 proteinases. AB - Kinetic constants (Km,Kcat) are derived for the hydrolysis of a number of chromogenic peptide substrates by the aspartic proteinase from HIV-2. The effect of systematic replacement of the P2 residue on substrate hydrolysis by HIV-1 and HIV-2 proteinases is examined. PMID- 2203351 TI - Spastic dysphonia simplified. PMID- 2203350 TI - Affinity purification of HIV-1 and HIV-2 proteases from recombinant E. coli strains using pepstatin-agarose. AB - A procedure is described which employs pepstatin-agarose for the affinity purification of either HIV-1 or HIV-2 protease from two similar recombinant E. coli constructs that were developed for the expression of these enzymes. HIV-2 protease was routinely expressed at much higher levels than the HIV-1 enzyme and pepstatin-agarose was the only chromatography step required to isolate pure HIV-2 protease from crude bacterial lysates. A Mono S ionic exchange step following pepstatin-agarose chromatography was sufficient to bring the HIV-1 protease to homogeneity. Purification of either enzyme can be completed in several days yielding homogeneous preparations suitable for crystallization and other physical characterization. PMID- 2203352 TI - Marketing as a public service. PMID- 2203353 TI - The common sense of marketing. PMID- 2203354 TI - Ethics, nostrums, and quackery. PMID- 2203355 TI - Marketing in the schools: a class act. PMID- 2203356 TI - Private practice is "seeing the people". PMID- 2203357 TI - Stop the presses! PMID- 2203358 TI - HELPLINE: ASHA on call. PMID- 2203359 TI - Recruiting: marketing the professions. PMID- 2203360 TI - Emerging issues for the professions in the 1990s. AB - Responses to the 1990 Omnibus Survey give information about how ASHA members will fare in the coming decade. In a period when employment stability and educational preparation are important issues, ASHA members enjoy a great deal of employment stability and think they have received adequate educational preparation. However, because nearly one third of ASHA members work in private practice, many may be responsible for purchasing their own health insurance and, therefore, may be particularly concerned with soaring medical costs in the future. As our way of life changes, ASHA members change with it. They are having smaller families and nearly half are interested in acquiring non-English language skills to keep pace with increased language diversity in the U.S. The demographic characteristics of ASHA membership, including the ratio of males to females, average age, and racial/ethnic background have remained stable over the past several years. The dynamics of the profession can be discerned, however, through an analysis of opinions on professional issues such as mandatory continuing education requirements, entry-level degree requirements for certification and specialty certification. On the whole, ASHA members indicate they would accept mandated continuing education requirements to maintain their Certificate of Clinical Competence, they prefer to keep the master's degree as the degree required for clinical certification and they do not favor ASHA moving in the direction of specialty certification. ASHA members reported that they are satisfied with the job the Association is doing in serving its members. They would like to learn about related professions through ASHA publications and nearly half sought professional interaction at an ASHA Annual Convention in the past 5 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203361 TI - Identification and partial characterization of diagnostically relevant antigens of Aspergillus fumigatus. AB - Metabolic antigens of Aspergillus fumigatus, soil strain 2605 and sputum isolate, were evaluated for their diagnostic applicability using hyperimmune sera and sera of adults and pediatric patients of allergic bronchopulmonary aspergillosis. An indirect ELISA was standardised by using 2-10 micrograms/ml of coating antigen for detection of specific IgG and IgE antibodies in the sera of patients. The ratios of absorbance for specific IgE and IgG antibodies by ELISA (normal to patients) were observed to be in the range of 1:2 to 1:3 to 1:8 respectively. These antigenic preparations were further analyzed to identify and characterize the individual components by immunoblotting. This analysis indicated the presence of allergenic and antigenic determinants in the antigens of molecular weights 70, 34, and 28 Kd. The utility of the antigens of soil strain for diagnostic purpose is suggested. PMID- 2203362 TI - Comparison of IgM, IgG and IgA responses to M.leprae specific antigens in leprosy. AB - Antibodies of IgM, IgG and IgA classes against M.leprae specific antigens (PGL-I, ND-O-BSA, and NT-O-BSA) were determined in the sera of 80 leprosy patients (28 untreated, 34 treated lepromatous and 18 tuberculoid), 25 tuberculosis patients and 33 normal individuals of Northern Thailand. No strong distinction in reactivity could be found between the three antigens. The IgM antibody assay yielded more positive results than assays for IgG and IgA. It was found that the positivity rates of IgM antibodies to all three antigens were highest in untreated lepromatous leprosy (82%). In tuberculoid leprosy, the positivity rates of IgM, IgG and IgA to the antigens were more variable, ranging from 22 to 50 percent. Patients with tuberculosis and normal individuals did not produce IgM antibodies against the antigens. The results suggested that the determination of IgM against the three antigens is a more sensitive and specific test for active leprosy than those of IgG and IgA. The relationship between the duration of treatment and IgM antibody levels in lepromatous leprosy (LL) was studied. Untreated LL patients had significantly higher IgM and IgA antibody levels than treated patients. There was no difference in IgG antibody levels between the two groups, and the levels of both groups were higher than normal controls. Serial determination of IgM antibodies in 7 LL patients revealed that treatment was strongly associated with progressive decrease in IgM antibody levels against all three antigens. PMID- 2203363 TI - Antibody engineering: current status and future development. PMID- 2203364 TI - On the relationship between type I hypersensitivity and cancer: a review. PMID- 2203365 TI - [Denture stomatitis. Its relation to candida albicans]. AB - One of the most usual complications of the patients that carry a prosthesis is one called stomatitis denture. Its etiology is not clear enough. In this work we study ninety people, sixty of them wear prosthesis. We take samples of different places in the mouth to plate and class C. Albicans. We look for the relationship of results with the clinical parameters of the patient. PMID- 2203366 TI - [Dental malocclusions in children with cerebral palsy]. AB - The purpose of this research is to compare the prevalence of dental malocclusions in a group of Cerebral Palsy children and a group of normal children. Throughout this investigation it was seen that Cerebral Palsy children have a greater tendency toward a Class II malocclusions and Open Bite. PMID- 2203367 TI - [Transversal problems]. AB - In this worn we introduce the alterations of the occlusion in the horizontal level or transversal problems, in which lateral crossed bites appear, either with or without a deviation of the medium line, underlying its differential diagnostic and guide lines treatment through several different clinic cases. PMID- 2203368 TI - [Evolution of facial and dental pain in the treatment of chronic maxillary sinusitis]. PMID- 2203369 TI - [Brain function monitoring]. AB - EEG and multimodal evoked potentials are currently the most frequently used methods of brain functioning monitoring in severely acute primary or secondary brain damage. Development or regression of brain function disturbances can be reliably assessed in this way. The methods are suitable for early diagnosis of intracranial complications and contribute to diagnosis of irreversible loss of cerebral function. They are also useful for early prognosis assessment. EEG and evoked potentials can be monitored at the bed-site. If there are no technical facilities for long-term EEG monitoring, repeated conventional single tracings are of value in these cases. When both the acoustic evoked brain stem potentials and the early somatosensory potentials are to be examined, the possibility exists to differentiate between hemispheric and brain stem damage and to use these results for prognosis assessment. PMID- 2203370 TI - [Environment and occurrence of epidemics]. AB - Epidemic diseases are defined as the temporary accumulation of dangerous infections diseases in certain areas. They are based on the principles of monocausality of Henle and Koch and represent the most important group of monocausal infectious diseases. Tight ecological relations exist between epidemic diseases and environment. The ecosystem encloses all living organisms as well as the inanimate environment (e.g. soil, water, air, waste). Some chains of infections are demonstrated with American equine encephalitis, rabies, Aujeszky's disease, salmonellosis and so-called soil-born epidemic diseases as examples. Any change of the environment causes enduring effects on the development and progression of epidemic diseases. Many epidemic diseases correlate with certain geographical zones. The variation of climate for instance led to an alteration of the occurrence of epidemic diseases caused by streptococci and staphylococci. A further evidence for the relation of environment and occurrence of epidemic diseases are the seasonal and secular rhythmics in the progress of epidemic diseases. On the basic of new techniques (finger-printing, hybridisation, sequence analysis) the origin of new types of infectious diseases such as American equine encephalitis and infections with Parvo- and Corona viruses can be explained. Finally medicine has to face this thesis: In contrast to the Darwinian theory the recombination of two different infectious agents in a common host may cause evolutionary jumps. PMID- 2203371 TI - [Cryptosporidiosis. Characterization of a new infection with special regard to water as the source of infection]. AB - Within the past few years, microorganisms of the Genus Cryptosporidium have been recognized as an important pathogen to humans. A possible mode of transmission is represented by the presence of Cryptosporidium-oocysts in water. Meanwhile several outbreaks of diarrheal illness caused by the contamination of drinking water by Cryptosporidium have been documented; an infection can be life threatening for immunosuppressed patients. This article reviews the organism causing Cryptosporidiosis, his ecology, the clinical feature, the sources of infection and the epidemiology. The remarkable resistance of the oocysts to disinfectants, such like chlorine, their survival for a long time and the low infectious dose shows evidently that the conservative guidelines in treatment and quality control of drinking water should be discussed newly. PMID- 2203372 TI - [Threshold values for chemicals to prevent disease]. AB - Proper interpretation of threshold limit values should always take into account that such limits are not absolute, but rather subject to change depending on advances in scientific knowledge. Threshold limit values derived from toxicologic study are best suited to evaluation of health risks of chemicals in the environment. Although more toxicologic information than is currently available would be desirable for the establishment of limit values, this should not prevent agreement on limits for more substances. "Better" threshold limit values would be forthcoming from epidemiologic studies, which are particularly rare in the FRG. Prospective studies measure current exposure; but appearance of detrimental health effects generally requires a lengthy latency period (e.g., decades in the case of cancer or cardiovascular disease). Threshold limit values permit monitoring and, if necessary, restriction of anthropogenic activity. Such restrictions are necessary, as shown by severe health damage which has occurred in the past (e.g., angiosarcoma due to vinyl chloride or neurogenic damage due to mercury in the workplace, tumors due to arsenic in drinking water, and methemoglobinemia in infants due to nitrite or renal damage due to cadmium in food). Evaluation of potential detrimental health effects for threshold limit values in environmental media is difficult because the effective dose cannot be determined. Monitoring of such limit values, which have already been incorporated into West German law, is relatively easy to implement, however (e.g. continuous outdoor air quality sampling and measurement, and periodic analysis of drinking water and foodstuffs). Since such monitoring may be performed close to the source, preventive measures should be easy to implement. Biological threshold limit values (biological monitoring) are essential to effective evaluation of the health effects of chemicals. Such limits should be established for more substances. When biological limit values are exceeded, however, it is generally difficult to determine the source(s) of exposure. Since individuals themselves cause the most damage to their own health e.g., through consumption of alcoholic beverages, cigarette smoking, or poor eating habits; the establishment of threshold limit values designed to protect individuals from themselves would be the most effective method of preventing environmental disease. PMID- 2203373 TI - Ultraviolet disinfection of drinking water. 1. Communication: Inactivation of E. coli and coliform bacteria. AB - The inactivation of E. coli and coliform bacteria by UV rays was tested in a laboratory unit. The strains investigated were E. coli ATCC 11229, C. freundii ATCC 8090, E. cloacae ATCC 13047 and K. pneumoniae ATCC 4352. The irradiation dose was determined by a modified potassium ferrioxalate actinometer according to Calvert and Pitts. In consequence with the investigations E. cloacae ATCC 13047 proved to be the most UV resistant and K. pneumoniae ATCC 4352 to be the most UV sensitive microorganism. PMID- 2203374 TI - [Systemic conditions and the periodontium. Review of basic concepts]. PMID- 2203376 TI - [Cylindrical posts: some types in wide use]. PMID- 2203375 TI - [Impressions for orthodontic study models]. PMID- 2203377 TI - [New type of cylindrical-conical post: the Cytco post]. PMID- 2203378 TI - [Dimension, form and color in anterior teeth]. PMID- 2203379 TI - [New system of provisional reinforcement in acrylic]. PMID- 2203380 TI - [Cylindrical posts: the Radix Anker system]. PMID- 2203381 TI - [Amalgam restoration of a devitalized tooth]. PMID- 2203382 TI - Procaine (Gerovital): no effect on the rehabilitation result in patients with back or hip disease. AB - Gerovital was compared with placebo and another procaine preparation in a double blind study of 88 rehabilitation patients suffering from back or hip disease. In an open part of the study procaine from intramuscularly injected Gerovital disappeared from the plasma within 15-30 minutes. In patients treated with Gerovital or another procaine no clinical, physiological or psychological benefits were found in addition to the improvements following rehabilitation compared with placebo treatment. Clinical examination showed that the benefits of rehabilitation were similar in patients receiving Gerovital, another procaine and placebo. PMID- 2203384 TI - Evidence for a primary role of insulin resistance in the pathogenesis of type 2 diabetes. AB - Although the primary defect(s) responsible for the development of type 2 diabetes still is unknown, several recent cross-sectional and longitudinal studies have clarified the sequence of events leading to type 2 diabetes. Relatives of type 2 diabetic patients, who have normal glucose tolerance, are characterized by hyperinsulinemia and insulin resistance compared to relatives with no family history of diabetes. In individuals with impaired glucose tolerance, insulin resistance is more severe than in those with normal glucose tolerance. The acute insulin response is lower in subjects with impaired glucose tolerance than in those with normal glucose tolerance but the decrease in the acute insulin response is similarly related to increases in plasma glucose as in normal subjects. A high postprandial insulin concentration, as well as the degree of insulin resistance, predicts the transition of glucose tolerance from impaired to diabetic. These data suggest that hyperinsulinemia and insulin resistance rather than insulin deficiency predict the subsequent development of type 2 diabetes in individuals genetically susceptible to the disease. As insulin resistance can be ameliorated with therapeutic measures such as weight loss and exercise, apparently healthy individuals with high insulin concentrations and a family history of type 2 diabetes might be regarded as a high-risk group which will require intensive attention from health care professionals. PMID- 2203383 TI - Some experiments on factors that can change insulin sensitivity. AB - Local hormones such as adenosine or prostaglandins can dramatically change the sensitivity of glucose transport in muscle to insulin. It is possible that these factors may play a role in changes in insulin sensitivity in vivo produced by such diverse conditions as treatment with furosemide, thyroid status or catecholamine status. In particular, there is evidence that chronic elevation of catecholamine or sympathetic stimulation improves insulin sensitivity. Evidence is also available to support the view that elevation of plasma catecholamine concentrations results in increased thermogenesis through activation of substrate cycling in a number of tissues. Consequently, insulin resistance and decreased thermogenesis may be explained by decreased levels of catecholamines and/or a decreased sensitivity of skeletal muscle and perhaps other tissues to catecholamines or a decreased activity of the sympathetic nervous system. PMID- 2203385 TI - A rapid procedure to evaluate foreign DNA transfer into mammals. PMID- 2203386 TI - Protamine-histone replacement and DNA replication in the male mouse pronucleus. AB - The protamine to histone replacement in fertilized mouse eggs was studied by using antibodies to these proteins. Its course was followed with respect to DNA replication by autoradiography of 3H-thymidine-labeled fertilized eggs. It was found that protamines were replaced by histones before the onset of DNA replication. PMID- 2203387 TI - Diadem/crater defects in spermatozoa from two related angus bulls. AB - The diadem/crater defect was studied over several months in two related 20-month old Angus bulls. In bull 1, diadem/crater defects were present in 2-99% of ejaculated spermatozoa at various times during the evaluation period. In bull 2, affected cells varied from 20% to 94%, with other abnormalities (head and acrosome defects, coiled tails, proximal cytoplasmic droplets) also common. Single sire mating trials conducted over 26 days during an apparent recovery phase showed normal fertility (approximately 50% pregnancies per estrus exposed). Both resting and gonadotropin-releasing hormone (GnRH)-stimulated testosterone values were within nor-mal limits. Histopathological evaluation of testes showed no obvious hypoplastic, inflammatory, or degenerative condition. Electron microscopy of ejaculated spermatozoa demonstrated the characteristic diadem pattern of craters in the equatorial region of the head. Many cells from bull 2 contained large craters in other regions of the nucleus. Electron microscopy of testicular tissue demonstrated nuclear invaginations lined by a single unit membrane in round spermatids. Lesions in elongated spermatids were more pronounced, with curling of the nucleus and large membrane-filled cavities in the chromatin occurring in addition to craters in the equatorial region of the nucleus. PMID- 2203388 TI - [Retrograde cardioplegia: advantages and shortcomings]. PMID- 2203389 TI - [The first clinical experience with heart transplantation]. AB - The article analyses the first clinical experience in orthotopic allotransplantation of the heart at the Scientific Research Institute of Transplantology and Artificial Organs, USSR Ministry of Health, in the period from October, 1986 to July, 1989 (26 transplantations of the heart and one two stage transplantation of the heart with the use of "Poisk-10M" artificial heart for 3.5 days in the first stage). Eleven patients are alive. Follow-up periods: maximum over 2.5 years, minimum 3 months. Sixteen patients died in different periods (up to 12 months). Three-component therapy (cyclosporine A, methylprednisolone, azathioprine) was applied for immunosuppression. The authors analyse the problems of the selection of potential recipients (indications and contraindications) and donor, the optimum surgical techniques, complications of immunosuppressive therapy, and infectious complications. The first clinical experience in two-stage transplantation of the heart is analysed. The first experience in transplantation of the heart in patients allows the conclusion that the use of this method for the management of the terminal stage of congestive cardiac insufficiency is a reality. PMID- 2203390 TI - [Vertical tooth fractures]. PMID- 2203391 TI - [Delayed cellular hypersensitivity against C. albicans in patients wearing dentures]. PMID- 2203392 TI - [New concepts in adhesive dentistry (3). Acid etching. Placement. Finishing and polishing of composite resins]. PMID- 2203393 TI - [Results of a survey of an elderly institutionalized population. 3. A group of elderly with remaining teeth and denture wearers]. AB - It has been carried out an inquest in a geriatric group in institutionalised regime, classifying people interviewed depending on dental health in three groups: Group I: Edentate ancients bearers of total prosthesis. Group II: Ancients with remanent pieces. Group III: Ancients with remanent pieces and bearers of prosthesis. In the present work, all findings related to oral health are detailed, referred uniquely to group III: Ancients with remanent pieces and bearers of prosthesis. Obtained data let us get to some conclusions we consider must be of general diffusion for trying to understand and to solve the existing disputable in this segment of the population, so long forgotten and marginal. PMID- 2203394 TI - [Oral diseases of Louis XIV]. PMID- 2203395 TI - Ultrasound and coarctation of the aorta. PMID- 2203396 TI - ST segment changes as a surrogate end point in coronary thrombolysis. PMID- 2203397 TI - Enhanced thrombolytic efficacy and reduction of infarct size by simultaneous infusion of streptokinase and heparin. AB - Because paradoxical increase in thrombin activity was reported after the administration of streptokinase in patients with acute myocardial infarction the velocity of reperfusion and degree of myocardial damage were studied when heparin was infused during rather than after streptokinase infusion. Thirty seven consecutive patients with acute myocardial infarction were randomised to receive intravenous heparin during (group 1, n = 18) or after (group 2, n = 19) streptokinase (1.5 megaunits over 60 minutes). Markers of reperfusion were monitored every 15 minutes for 3 hours. The serum concentration of creatine kinase was measured every 2 hours. The two groups were similar in terms of age and sex distribution, infarct site, time to treatment, and baseline myocardial ischaemia. Patients in group 1 had a significantly shorter mean (SD) reperfusion time (57 (35) minutes v 101 (47)). From 60 to 120 minutes after randomisation there were significant differences in ST segment elevation between the groups. Serum creatine kinase MB peaked earlier (8 (2) hours) in group 1 than in group 2 (10 (4) hours). The peak concentration was significantly lower in group 1 (87 (47) mU/ml) than in group 2 (134 (96) mU/ml) and infarcts were smaller (25.2 (9.8) gram equivalents/m2) in group 1 than in group 2 (35.1 (10.2) gram equivalents/m2). Simultaneous infusion of heparin and streptokinase speeds up the appearance of signs of reperfusion and reduces infarct size. PMID- 2203399 TI - The AIDS education needs of adolescents: a theory-based approach. AB - The purpose of this study was to conduct an educational diagnosis for AIDS prevention among school age adolescents. The Health Belief Model was used as a conceptual framework to analyze adolescent beliefs that may influence HIV risk behavior. A statewide, stratified random sample of 7th, 9th, and 11th grade students was drawn during the Spring of 1988. Results reveal that adolescents' knowledge of AIDS and HIV transmission is superficial. Many adolescents hold serious misconceptions that could lead to unintentional risk behavior. High levels of fear were reported, yet students clearly misunderstood the seriousness of AIDS. Barriers to preventive actions were identified. Recommendations are made to increase the effectiveness of school-based HIV education. PMID- 2203400 TI - Cervical and thoracic pain including thoracic outlet syndrome and brachial neuritis. PMID- 2203398 TI - Samuel A Levine's first world war encounters with Mackenzie and Lewis. AB - Samuel Albert Levine was a key figure in modern cardiology in the United States. During the first world war he was one of a select group of United States medical officers assigned to the British Military Heart Hospital where he encountered the "British medical giants"--Clifford Allbutt, William Osler, James Mackenzie, and Thomas Lewis. Levine's diary, written when he was a young medical officer during the first world war, presents crisp character sketches of James Mackenzie and Thomas Lewis. The autobiographical vignettes he wrote later in life were more gracious and polished retrospectives. The Levine perspectives, separated by a half century, contribute to our understanding of the developing fabric of Anglo American cardiology. PMID- 2203401 TI - Peripheral nerve entrapments, repetitive strain disorder, and occupation-related syndromes. PMID- 2203402 TI - Shoulder pain and reflex sympathetic dystrophy. PMID- 2203403 TI - Bursitis, tenosynovitis, ganglions, and painful lesions of the wrist, elbow, and hand. PMID- 2203404 TI - Fibromyalgia and chronic fatigue syndrome. PMID- 2203405 TI - Knee extensor mechanism disorders. PMID- 2203406 TI - Epidemiology of the rheumatic diseases. PMID- 2203407 TI - Methods of clinical measurement. PMID- 2203408 TI - Recent clinical pharmacology and clinical trial reports. PMID- 2203409 TI - Rehabilitation and biomechanics. PMID- 2203410 TI - Health care research and technology. PMID- 2203411 TI - Patient education in rheumatoid arthritis. PMID- 2203412 TI - Pain management. PMID- 2203414 TI - Contrast radiology. PMID- 2203413 TI - Radiologic features of rheumatic disorders. PMID- 2203415 TI - Ultrasonography and computed tomography. PMID- 2203416 TI - Nuclear medicine techniques. PMID- 2203417 TI - Densitometry and bone mineral measurement. PMID- 2203419 TI - Miscellaneous rheumatic conditions. PMID- 2203418 TI - Technology evaluation and clinical trials of magnetic resonance imaging. PMID- 2203420 TI - Epidemiology and health services research. PMID- 2203421 TI - Imaging in rheumatology. PMID- 2203422 TI - The immunogenetics of rheumatoid arthritis. PMID- 2203423 TI - Heat-shock proteins: a link between rheumatoid arthritis and infection? PMID- 2203424 TI - Neuroendocrine hormonal factors in rheumatoid arthritis and related conditions. PMID- 2203425 TI - Classification, clinical assessment, clinical features, and complications. PMID- 2203427 TI - Laboratory and radiologic investigations in the diagnosis and evaluation of rheumatoid arthritis. PMID- 2203426 TI - Differentiating rheumatoid arthritis from other arthropathies. PMID- 2203428 TI - Prognosis in rheumatoid arthritis. PMID- 2203429 TI - Conventional drug therapies and complications, novel therapies, and nondrug treatments. PMID- 2203430 TI - Therapy and mechanisms of nonsteroidal anti-inflammatory drugs, and pain management, acupuncture, and rehabilitation. PMID- 2203431 TI - Toxicity of nonsteroidal anti-inflammatory drugs. PMID- 2203432 TI - Immunosuppressive drug therapy. PMID- 2203433 TI - Novel therapies. AB - Extremely preliminary results from uncontrolled feasibility studies hint that minocycline and T-cell cytolitic strategies deserve further evaluation in RA, as does the use of high-dose intravenous gammaglobulin in chronic cutaneous vasculitis. PMID- 2203434 TI - Steroids. PMID- 2203435 TI - Rheumatoid arthritis. PMID- 2203436 TI - Clinical therapeutics. PMID- 2203437 TI - Acute effects of ultraviolet radiation on the skin. AB - The responses of normal skin to ultraviolet (UV) irradiation are an example of inflammation. The chromophores initiating the reaction are unknown. Characteristic clinical findings are erythema, heat, swelling, and pain. Histopathologic changes include epidermal keratinocyte damage with Langerhans cell depletion and dermal edema, endothelial swelling, mast cell degranulation, and cellular infiltration with neutrophils and monocytes. Biochemical changes include release of histamine, cyclo-oxygenase, and lipoxygenase-derived products of arachidonic acid, kinins, and cytokines, probably from a range of epidermal and dermal cell types. These substances very likely assist in mediation of the reaction. The response is more pronounced in young subjects. UVB (280 to 315 nm) and UVA (315 to 400 nm) radiation both produce inflammation, but with marked qualitative and quantitative differences. UVB having more effect on the epidermis, UVA more on the dermis. PMID- 2203438 TI - Photoimmunology. AB - Photoimmunology is the study of the effects of ultraviolet radiation (UVR) on immunologic processes. Most work has examined UVR effects in animal models and in vitro systems, with limited data from humans. UVB irradiation inhibits induction of immunity systematically at high doses and locally at low doses in animals, and is associated with the appearance of transferable T suppressor lymphocytes. Photosensitized UVA and visible irradiation can have similar effects. In some mouse strains, chronic UVB exposure leads to highly immunogenic cutaneous malignancies, which are able to escape immunologic destruction in part because of protection from suppressor T lymphocytes. Immunosuppressed patients also have increased rates of skin cancer, suggesting immunologic involvement in regulation of skin cancer development. UVB or psoralen photochemotherapy (PUVA) irradiation alters circulating lymphocyte subtypes and contact hypersensitivity responses in man. UVB irradiation also induces the appearance of epidermal non-Langerhans antigen presenting cells, which may have suppressive functions. In vitro UVR exposure decreases antigen presenting cell function, lymphocyte responses to mitogens or antigens, and lymphocyte viability. UVB irradiation of keratinocytes alters interleukin 1 (IL-1) production and induces the release of immunosuppressive factors. It is clear that even modest amounts of UVR alter immunologic function and human avoidance of prolonged sun exposure would seem prudent. PMID- 2203439 TI - Human exposure to ultraviolet radiation. AB - Although the sun remains the main source of ultraviolet radiation (UVR) exposure in humans, the advent of artificial UVR sources has increased the opportunity for both intentional and unintentional exposure. Intentional exposure is most often to tan the skin. People living in less sunny climates can now maintain a year round tan by using sunbeds and solaria emitting principally UVA radiation. Another reason for intentional exposure to artificial UVR is treatment of skin diseases, notably psoriasis. Unintentional exposure is normally the result of occupation. Outdoor workers, such as farmers, receive three to four times the annual solar UV exposure of indoor workers. Workers in many industries, eg, photoprinting or hospital phototherapy departments, may be exposed to UVR from artificial sources. One group particularly at risk is electric arc welders, where inadvertent exposure is so common that the terms "arc eye" or "welders flash" are often used to describe photokeratitis. In addition to unavoidable exposure to natural UVR, the general public is exposed to low levels of UVR from sources such as fluorescent lamps used for indoor lighting and shops and restaurants where UVA lamps are often used in traps to attract flying insects. PMID- 2203440 TI - Cumulative effects of ultraviolet radiation on the skin: cancer and photoaging. AB - The cumulative effects of solar exposure are skin cancer and photoaging. This relationship has been established by epidemiological, clinical, and pathological investigation. Understanding of the mechanisms of skin cancer and photoaging requires the study of model systems. For example, the study of cancerprone xeroderma pigmentosum patients has indicated that effective DNA repair is a major defence mechanism against skin cancer. However, there are few human models. The hairless albino mouse has been shown to be a good model for both photocarcinogenesis by ultraviolet radiation (UVR) alone and UVR in association with 8-methoxypsoralen and photoaging and may provide much information on mechanistic aspects. The use of sunscreens is often advocated as a means of preventing the cumulative effects of solar exposure. Animal data support this approach but such data must be interpreted with caution. PMID- 2203441 TI - The acute idiopathic photodermatoses. AB - The acute idiopathic photodermatoses are more common in females and comprise polymorphic light eruption, actinic prurigo, hydroa vacciniforme, and solar urticaria. Polymorphic light eruption occurs considerably more frequently than the others and while precise pathogenic mechanisms are still unclear, increasing evidence suggests an immunological basis for this condition. Although clinically distinct, actinic prurigo may be a variant of polymorphic light eruption, whereas solar urticaria and possibly hydroa vacciniforme are distinct entities, the former representing a type I hypersensitivity response. Polymorphic light eruption is characterized by a recurrent cutaneous reaction to ultraviolet (UV) exposure occurring after a delay of several hours that consists of pruritic erythematous papules, vesicles, or plaques on usually only some exposed sites and resolves without scarring over about a week. Actinic prurigo is differentiated from polymorphic light eruption by childhood onset and more persistent and excoriated lesions present both on sun-exposed and, to a lesser extent, non exposed sites. Hydroa vacciniform is a rare disorder that also begins in childhood, and is characterized by recurrent crops of vesicles on sun-exposed skin and subsequent vacciniforme scarring. Solar urticaria is an uncommon condition that usually begins in the third or fourth decade and is differentiated from the other acute idiopathic photodermatoses by rapid onset of urticarial lesions within minutes of UV exposure and resolution within 1 to 2 hours. PMID- 2203442 TI - Drug and chemical photosensitivity. AB - Chemical (especially drug-induced) cutaneous photo-sensitization is an increasing problem in dermatology. Various molecular, biochemical, and pathophysiologic processes are involved in translation of ultraviolet (UV) or visible radiation energy into phototoxic and/or photoallergic reactions in the skin. Phototoxicity presents in four major reaction patterns, depending on the target for photosensitization. Photoallergy is now confirmed as an immune system cell mediated photosensitization. Drug-induced photosensitivity is not necessarily a good reason for stopping therapy. Sunlight avoidance, appropriate protection with clothing, sunscreens, and drug dose reduction may allow continuation of treatment. However, future drug registration procedures may require more detailed testing both in vitro and in vivo, and good clinical trials for which suitable protocols are becoming available. PMID- 2203443 TI - Photosensitivity dermatitis and actinic reticuloid syndrome (chronic actinic dermatitis). AB - The photosensitivity dermatitis and actinic reticuloid syndrome (chronic actinic dermatitis) is a common eczematous photodermatosis of unknown aetiology that in severe form is an extremely disabling condition. It is unclear why males are particularly affected. Difficulties in diagnosis arise in patients who have perennial problems in whom clinical photosensitivity may not be volunteered. An additional problem for the clinician is the finding of contact allergy that is frequently multiple, which further complicates the clinical picture that may, in severe cases, present as an erythroderma or a pseudolymphomatous state. Patch testing and phototesting are the key investigations, with broad ultraviolet (UV) waveband sensitivity occurring as a dermatitis rather than a sunburn response. Contact allergy recognition and avoidance, along with photoprotective measures, are helpful in most cases. Photochemotherapy (PUVA) and systemic immunosuppression may be required in those patients who fail to respond. In some cases, spontaneous resolution follows after a number of years. PMID- 2203444 TI - DNA repair deficient photodermatoses. AB - Photosensitive genodermatoses associated with established defects of DNA repair currently include the autosomal recessive diseases xeroderma pigmentosum (XP), Cockayne's syndrome (CS), trichothiodystrophy (TTD), and Bloom's syndrome (BS). XP is a heterogeneous disorder associated with defective excision repair or daughter strand repair of ultraviolet (UV)-induced DNA damage. It is characterized by cutaneous and ocular abnormalities predominantly on sun-exposed sites and in some cases, neurological features resulting from progressive neuronal loss. Skin involvement includes easy sunburning, pigmentary abnormalities, telangiectasia, dryness, scarring, and susceptibility to multiple benign and malignant neoplasms. In CS, defective repair of actively transcribing DNA is clinically associated with acute photosensitivity, growth retardation, demyelinating neurological abnormalities, and pigmentary retinal degeneration, but without increased cancer susceptibility. TTD is characterized by sulphur deficient brittle hair, variable growth delay, mental retardation, ichthyosis, and in some cases photosensitivity. Although in some patients there is a deficiency of DNA excision repair identical to that in certain xeroderma pigmentosum patients, no increased cancer risk is present in trichothiodystrophy. In BS, deficient cellular DNA ligase is associated with congenital telangiectasia, photosensitivity, growth retardation, immune deficiency, increased susceptibility to infection, and predominantly internal rather than cutaneous malignancy. Immunological factors may at least determine the varying susceptibility to malignancy of these conditions. PMID- 2203445 TI - The cutaneous porphyrias. AB - The cutaneous porphyrias are disorders of heme biosynthesis in which excessive formation of porphyrins, secondary to partial enzyme deficiencies, produces photosensitization. There are five main types: porphyria cutanea tarda (PCT); variegate porphyria (VP); hereditary coproporphyria (HC); erythropoietic protoporphyria (EPP); and congenital erythropoietic porphyria (CEP). They can be differentiated by measuring heme precursors in urine, feces, erythrocytes, and plasma. VP, HC, EPP, and one form of PCT (type II) are autosomal dominant conditions with low clinical penetrance. The autosomal recessive prophyrias (CEP and homozygous counterparts of type II PCT, VP, and HC) are rare disorders. The skin lesions in PCT (the commonest cutaneous porphyria), VP, HC, and CEP are similar: mechanical fragility, subepidermal bullae, hypertrichosis, and pigmentation. EPP is characterized by acute photosensitivity without these lesions. Acute attacks of porphyria may occur in VP and HC but not in other cutaneous porphyrias. Liver disease is an uncommon, potentially fatal, complication of EPP. PCT is commonly associated with chronic liver disease, is often caused by alcohol and usually mild. PCT can be treated by repeated venesection to deplete iron stores or with low-dose chloroquine. Treatment of the other cutaneous porphyrias is largely symptomatic; accumulation of beta-carotene in the skin is particularly effective in EPP. PMID- 2203446 TI - The photoaggravated dermatoses. AB - The photoaggravated dermatoses are diverse diseases adversely affected by sunlight or artificial ultraviolet (UV) exposure. The role of UVR is often well recognized, as in lupus erythematosus (LE) and bullous pemphigoid (BP). Immunologic theories for the cause of the photosensitivity in lupus erythematosus are the production of UV-DNA antibodies with subsequent immune complex formation, a partial defect in DNA repair following UV exposure, and the release or stimulation of potent cutaneous immunologic mediators. However, mechanisms are still not fully elucidated. Photosensitivity has also been described in erythema multiforme, actinic lichen planus, viral exanthems, cutaneous T-cell lymphoma, eczema, and psoriasis. Treatment is restriction of light exposure, use of high protection sunscreens, and treatment of the underlying disorder. PMID- 2203447 TI - Photoprotection. AB - Sunscreens are agents that attenuate the effects of ultraviolet radiation on the skin by absorption or reflection of part of the incident radiation or by interception of harmful products of its interaction with the Sunscreens may be applied topically or ingested; however, topical agents are by far the more common and effective and only they will be discussed in this report. Topical sunscreens are formulated as creams or lotions and are characterized by their sun protection factor, a measure of their efficacy against sunburning and their substantivity, their resistance against removal after application. PMID- 2203448 TI - Phototherapy and photochemotherapy. AB - This is a review of present knowledge of the use of ultraviolet (UV) radiation in the treatment of skin diseases. Two methods are currently used: phototherapy with UVB, and photochemotherapy with UVA and psoralens as photosensitizers. Both forms have their place in dermatologic therapy. In particular, photochemotherapy has become a standard treatment for severe psoriasis, mycosis fungoides, vitiligo, and some other dermatoses; it is effective as prophylactic treatment in polymorphic light eruption and other photodermatoses. This report will focus on indications, possible mechanisms, and treatment results. In addition, the potential acute and chronic side effects of these therapies are reviewed with special emphasis on skin carcinogenesis. PMID- 2203449 TI - Experimental embryology in France (1887-1936). PMID- 2203450 TI - Protein phosphorylation during meiotic maturation of Xenopus oocytes: cdc2 protein kinase targets. AB - M-Phase specific protein kinase or cdc2 protein kinase is a component of MPF (M Phase promoting factor). During meiotic maturation of Xenopus oocytes, cdc2 protein kinase is activated in correlation with MPF activity. A protein phosphorylation cascade takes place involving several protein kinases, among which casein kinase II, and different changes associated with meiosis occur such as germinal vesicle breakdown, chromosome condensation, cytoskeletal reorganization and increase in protein synthesis. Our results provide a biochemical link between cdc2 protein kinase and protein synthesis since they show that the kinase phosphorylates in vitro a p47 protein identified as elongation factor EF1 (gamma subunit) and that the in vitro site of p47 corresponds to the site phosphorylated in vivo. Immunofluorescence showed that the elongation factor (EF1-beta gamma) is localized in the oocyte cortex. Furthermore, they show that cdc2 kinase phosphorylates and activates casein kinase II in vitro, strongly supporting the view that casein kinase II is involved in the phosphorylation cascade originated by cdc2 kinase. PMID- 2203451 TI - Calcium in sea urchin egg during fertilization. AB - Calcium plays a strikingly important role in two of the major events in developmental biology: cell activation and differentiation. In this review we begin with the location and quantity of intracellular calcium in sea urchin oocytes, and then discuss the changes that occur during fertilization and egg activation, placing special emphasis on the mobilization and redistribution of intracellular calcium. We also discuss the propagation of the calcium wave and the role of the burst of calcium on the process of reorganizing the egg cortex at fertilization. PMID- 2203452 TI - Cytoskeleton organization during oogenesis, fertilization and preimplantation development of the mouse. AB - The organization and role of the cytoskeletal networks (mainly microtubules and microfilaments) during oogenesis, fertilization and preimplantation development of the mouse are described given the importance of cell-cell interactions and of the subcellular organization in events leading to the formation of the first two lineages of the mouse embryo. PMID- 2203453 TI - Fibronectin-rich fibrillar extracellular matrix controls cell migration during amphibian gastrulation. AB - We have reviewed the evidence supporting the notion that the fibrillar extracellular matrix on the basal surface of the blastocoel roof in amphibian embryos directs and guides mesodermal cell migration during gastrulation. Based on extensive experimental evidence in several different systems, we conclude the following: (i) the fibrillar extracellular matrix contains fibronectin (FN) and laminin. (ii) The fibrils are oriented in such a way as to promote directional migration of mesodermal cells during migration. (iii) We have used several different probes to disrupt the interaction between migrating mesodermal cells and the fibrillar extracellular matrix. These probes include: (a) nucleocytoplasmic and interspecific hybridization. Such embryos have defects in FN synthesis and gastrulation. (b) Fab' fragments of anti-FN and anti-integrin VLA-5 IgGs prohibit mesodermal cell adhesion both in vitro and in vivo and gastrulation is arrested. (c) Peptides containing the RGDS sequence specifically inhibit interactions between migrating mesodermal cells and the FN-fibrillar matrix. (d) Tenascin blocks cell adhesion to FN in vitro and gastrulation in vivo. (e) Antibodies against the cytoplasmic domain of beta 1 integrin, when injected into blastomeres, prevent FN-fibrillogenesis in progeny of injected blastomeres and delay mesodermal cell migration selectively in the progeny of injected blastomeres but not in the uninjected blastomere progeny. PMID- 2203454 TI - From presumptive ectoderm to neural cells in an amphibian. AB - As an immediate consequence of neural induction during gastrulation, some neuroectodermal cells acquire the ability to develop a number of specific neuronal and astroglial features, without requiring subsequent chordamesodermal cues. Thus, cholinergic, dopaminergic, noradrenergic, gabaergic, somatostatinergic, enkephalinergic, etc. traits are expressed in cultures of neural plate and neural fold isolated from amphibian late gastrulae immediately after induction and cultured in a defined medium. These results strongly suggest that at the late gastrula stage, the neural precursor population does not yet constitute a homogeneous set of cells. It was of interest to know the origin of this heterogeneity. Is it a direct result of the process of neural induction itself, stochastic phenomena being involved or not at the cellular level, or does it reflect a pre-existing heterogeneity in the presumptive ectoderm? At the early gastrula state, presumptive ectoderm can be neuralized consecutively to its dissociation into single cells. Using this experimental model, we have demonstrated by means of immunological probes that neuralized presumptive ectodermal cells, without any intervention of the chordamesoderm (natural inducing tissue), can develop autonomously into glial and neuronal lineages. These data suggest the existence of diverse predispositions of presumptive ectodermal cells. Competent ectoderm seems to be a heterogeneous structure with cells presenting distinct neural predispositions that can emerge as a consequence of a permissive inductive signal without real specificity (such as a target tissue dissociation). Moreover, such a differentiated neuronal population includes neurons of the GABAergic and enkephalinergic phenotypes but not of the cholinergic, catecholaminergic, somatostatinergic, etc. phenotypes. These data show that the developmental program of ectodermal cells induced without interaction with the chordamesoderm appears restricted compared to the naturally induced ectoderm. Experiments are now under way to analyze such sequential neural events. PMID- 2203455 TI - The avian neural crest as a model system for the study of cell lineages. AB - Under the influence of environmental factors, the neural crest gives rise to numerous cell types and is therefore, by definition, a pluripotential structure. However, it was not clear until recently to what extent each individual neural crest cell possessed multiple capacities for differentiation. As a result of in vivo and in vitro approaches aimed at solving this problem, it has become apparent that the neural crest is made up of cells in different states of determination and that some lineages are segregated very early. In particular, analysis of clones obtained from single cells grown in culture has shown that, although many individual neural crest cells are pluripotential to varying degrees, others are apparently committed to give rise to only one derivative. The role of the embryonic microenvironment in the emergence of phenotypic diversity is probably complex, certain factors acting to promote the survival of selected subpopulations of fully determined progenitors, while others may direct partly committed precursors towards a specific developmental fate. PMID- 2203456 TI - Characterization of myogenesis from adult satellite cells cultured in vitro. AB - We describe several characteristics of in vitro myogenesis from adult skeletal muscle satellite cells from the rat and several amphibian species. The timing of cell proliferation and fusion into myotubes was determined, and in urodeles, myogenesis from satellite cells was clearly demonstrated for the first time. Growth factors are known to stimulate satellite cell proliferation. Acidic FGF mRNA was present in rat satellite cells during proliferation but it was not detected in myotubes. Fibronectin was synthesized in satellite cells during proliferation and expelled into the extracellular medium when the myotubes differentiated. We suggest that fibronectin plays a part in the formation of myotubes, as this process was inhibited by anti-fibronectin IgG. Adult satellite cells might differ from fetal myoblasts since they were observed to exhibit the opposite response to a phorbol ester (TPA) to that of the myoblasts. We therefore examined the possibility that the different levels of protein kinase C activity and different phorbol ester binding characteristics in the two cell types account for these opposite responses. Our results suggest that the difference is not connected with the phorbol ester receptor but might be caused by events subsequent to protein kinase C activation. Localized extracellular proteolytic activity might have a role in cell mobilization and/or fusion when satellite cells are activated. We showed that the content of plasminogen activators, chiefly urokinase, was larger in tissues from slow twitch muscles which regenerate more rapidly than fast muscles. The urokinase level rose sharply in cultures when cells fused into myotubes, and was twice as high in slow muscle cells as in fast ones. We also found that, in vitro, slow muscle satellite cells displayed greater myogenicity, but that phorbol ester inhibited their mitosis and myogenicity. We conclude that satellite cells acquire characteristics which differentiate them from myoblasts and correspond to the fast and slow muscles from which they originate. PMID- 2203457 TI - Spinal cord-muscle relations: their role in neuro-muscular development in birds. AB - In the present study we focused our attention on the role of spinal cord-muscle interactions in the development of muscle and spinal cord cells. Four experimental approaches were used: 1) muscle fiber-spinal cord co-culture; 2) chronic spinal cord stimulation in chick embryos; 3) direct electrical stimulation of the denervated chick muscle; 4) skeletal muscle transplantation in close apposition to the spinal cord in chick embryos. The characteristics of mATPase and energetic metabolism enzyme activities and of myosin isoform expression were used as markers for fiber types in two peculiar muscles, the fast twitch PLD and the slow-tonic ALD. In vitro, in the absence of neurons, myoblasts can express some characteristics of either slow or fast muscle types according to their origin, while in the presence of neurons, muscle fiber differentiation seems to be related to the spontaneous rhythm delivered by the neurons. The in ovo experiments of chronic spinal cord stimulation demonstrate that the differentiation of the fast and slow muscle features appears to be rhythm dependent. In the chick, direct stimulation of denervated muscles shows that the rhythm of the muscle activity is also involved in the control of muscle properties. In chick embryos developing ALD, the changes induced by modifications of muscle tension demonstrate that this factor also influences muscle development. Other experiments show that muscle back-transplantation can alter the early spinal cord development. PMID- 2203458 TI - Development of the vertebrate small intestine and mechanisms of cell differentiation. AB - The intestinal epithelium represents an attractive biological model of differentiation from stem cells to highly differentiated epithelial cells, not only during particular developmental events depending upon the vertebrate species considered but also throughout adult life. The ontogenic maturation of the intestinal epithelium arises from both a programmed expression of specific genes and epigenetic influences mainly due to epithelial and mesenchymal interactions and hormonal participation. In the present paper we review the structural and functional changes that occur in the amphibian, avian and mammalian intestine during embryonic and/or post-embryonic development. Furthermore, we review the data concerning the mechanisms which control the cytodifferentiation of the intestinal epithelium. PMID- 2203459 TI - Cell interactions and regeneration control. AB - This paper is a review of the main findings of our laboratory on the control of regeneration by cell interactions. These include results related to the role of both cell contact and local soluble factors in regeneration of the legs of insects and newts and of the parapodia and segments of nereis. The pattern of these structures is considered to be defined by positional information distributed as longitudinal and transverse positional value sequences carried by epidermal (insect) or mesenchymal (newt) cells. By associating tissues to create transverse and longitudinal discontinuities in these sequences, single or multiple regenerating structures were obtained. These structures are formed by the intercalation of cells characterized by intermediate positional values which fill the gap between the tissues in contact. Positional information may also be changed during regeneration by the nerve cord in nereis and retinoids in the newts. We describe additional cases where morphogenesis occurs without any overt discontinuity in positional information, such as from a locally injured or non injured insect trochanter, or after deflection of nerves in nereis and newt. Regeneration following an amputation may be considered as a special case of intercalary regeneration, the first stage being the juxtaposition of normally non contiguous cells resulting in a longitudinal or/and a transverse gap. We also report studies on local factors produced by nerves and the blastema during newt limb regeneration. The nerve factor is necessary for the division of blastemal cells. After denervation, mesenchyme differentiates in an abnormal way. The mitogenic signal from the nerves is mediated by the PKC pathway. Its production is enhanced by regeneration of cut nerve fibers. The blastema also produces growth factors. We show that the epidermal cap and mesenchyme contain acidic FGF like factor, and that the proliferating mesenchyme stimulates nerve fibers to regrow into the blastema. PMID- 2203460 TI - Developmental mechanism involved in the embryonic reduction of limbs in reptiles. AB - The purpose of the studies here reported was to explain the mechanisms responsible for the reduction of limbs in the serpentiform reptiles. Descriptive and experimental embryology, ultrastructural studies, chemical action (with Ara C) on embryos and (3H) thymidine autoradiography of limb buds were used in this study; they provide evidence that defects in the morphogenetic mechanisms involved in the development of limbs (somitic deficiency, incomplete differentiation and premature degeneration of the apical ectodermal ridge) are responsible for the cessation of growth of the limb buds in these reptiles. At the biochemical level, a strong decline in the rate of DNA synthesis in the mesodermal cells of the limb bud (during and after the degeneration of the apical ridge) is the main causative factor of the evolutionary arrest of limb development in serpentiform reptiles. PMID- 2203461 TI - Lineus as a model for studying developmental processes in animals reconstructed from adult pieces. AB - The difficulties that prevent reconstruction of animals by piecing together body fragments from several adults are overcome by using nemerteans of the genus Lineus. For 25 years I have managed to make viable composite worms by grafting body parts cut out of Lineus specimens either from the same clonal strain (syngeneically reconstructed worms) or from the same species (allogeneically reconstructed worms) or else from different species (xenogeneically reconstructed worms). Body reconstruction has usually been carried out orthotopically, i.e., the components of composite animals have been selected so as to be anatomically complementary. However, reconstruction has been made heterotopically when it was essential to obtain morphogenetic events in the adults. Here, I shall review some of the developmental processes that took place in such reconstructed animals. First, I shall report immune responses in composite worms derived from various combinations of body pieces grafted together. Second, I shall study sex differentiation during gonad development in growing or regenerating chimeric worms made by the grafting of male and female components. I shall refer also to gonadogenesis in the asexual progeny of bipartite chimeras derived from lateral body halves of both sexes fused together (clones of bilaterally allophenic worms). Third, I shall analyze regulative processes (regeneration, transgeneration) during localized morphogenesis occurring in heterotopically reconstructed worms. The data show how reconstructed Lineus may be exploited to increase our knowledge of developmental mechanisms, especially in the misunderstood field of organismal pattern homeostasis. PMID- 2203462 TI - On the present situation of developmental biology in France. PMID- 2203463 TI - Pattern formation in skin development. AB - The development of skin and cutaneous appendages in amniote embryos has been submitted to a large number of experimental investigations the results of which have led to a better understanding of the mechanisms whereby this multiform organ arises during embryonic development. In birds, the main appendages are the feathers and the foot scales. Their formation results from a series of inductive events between ectoderm (later epidermis) and subectodermal mesoderm (later individualized dermis). Morphogenetically, the mesodermal (mesenchymal) component of skin is the predominant tissue, insofar as it controls most morphological and physiological features of developing skin and appendages, notably transformation of ectoderm into epidermis, polarization, proliferation and stratification of epidermal cells, initiation, site, size and distribution pattern of epidermal placodes, species-specific architecture of appendages, regional specification of keratin synthesis. The ectodermal (epithelial) component is able to respond to the mesodermal inductive instructions by building feathers and scales in conformity with the specific origin of the dermis. In these epithelial mesenchymal interactions, extracellular matrix and the microarchitecture of the dermal-epidermal junction appear to play an important role. Indeed extracellular matrix components (primarily collagens, proteoglycans and adhesive glycoproteins) and dermal cell processes close to the epidermal basement membrane become distributed in a microheterogeneous fashion, thus providing a changing substratum for the overlying epidermis. It is assumed that the latter is able to somehow sense the texture and composition of its substratum, and by doing so to appropriately engage in the formation of glabrous, feathered or scaly skin. PMID- 2203464 TI - Sex, differentiation and cancer. Interview by Francoise Dieterlen. PMID- 2203465 TI - Meiosis reinitiation as a model system for the study of cell division and cell differentiation. AB - In this paper, we review our findings concerning the control of meiosis reinitiation in starfish oocytes and discuss recent advances that lead to characterization of the maturation promoting factor (MPF) responsible for G2-M transition. It is now agreed that appearance of this factor, which triggers nuclear envelope breakdown, chromosome condensation and metaphase spindle formation, corresponds to the activation of a M-phase specific H1-kinase. MPF has been shown to be constituted of equimolar amounts of a 34 kDa catalytic subunit protein homologous to the yeast cdc2/CDC28 gene product and a cyclin protein homologous to the yeast cdc13 gene product. "In vivo" and "in vitro" studies based on the use of inhibitors of protein synthesis, protein kinases, phosphoprotein phosphatases and proteases lead to a better understanding of the complex series of events which regulate activation and inactivation of MPF. In the unfertilized metaphase 2-arrested vertebrate oocyte, it has also been shown that stabilization of MPF depends on the kinase activity of the c-mos protooncogene. This review attempts to illustrate how the significant progress made in the understanding of the regulation of cell cycle transverse directly resulted from the convergence of observations in multidisciplinary studies in yeast genetics, development and oncogenesis. It also offers a model for considering the highly integrated events which, starting at the level of the plasma membrane, may eventually result in early cell differentiation. PMID- 2203466 TI - Assessment of urinary protein 1 and transferrin as early markers of cadmium nephrotoxicity. AB - Transferrin and protein 1, a sex linked alpha 2-microprotein, were assayed in urine from 58 workers exposed to cadmium (Cd) in a non-ferrous smelter and from 58 age matched referents. These two new markers of nephrotoxicity were compared with urinary beta 2-microglobulin (beta 2-m), retinol binding protein (RBP), albumin, and beta-N-acetyl-glucosaminidase (NAG). The response of protein 1 to Cd tubulotoxicity was similar to that of beta 2-m, RBP, and NAG. In Cd workers, protein 1 had a correlation with urinary Cd (r = 0.56) similar to beta 2-m (r = 0.48), RBP (r = 0.58), and NAG (r = 0.49). Values of these three low molecular weight proteins and of NAG were increased only in workers with urinary Cd higher than 10 micrograms/g creatinine. Urinary transferrin and albumin were similarly affected by exposure to Cd. Their response, however, was clearly more sensitive than that of low molecular weight proteins. Prevalences of positive values of these two high molecular weight proteins were not only higher but also tended to rise at lower concentrations of Cd in urine or blood. This finding suggests that in some subjects subtle defects in glomerular barrier function may precede the onset of proximal tubular impairment after chronic exposure to Cd. It remains to be assessed whether these subjects are more at risk of developing renal insufficiency. PMID- 2203467 TI - Topical steroids in the treatment of central and paracentral corneal ulcers. AB - During an 18-month period a prospective randomised trial was conducted on 40 selected patients with bacterial corneal ulcers. Two groups were compared: one was treated with antibiotic only and the other with antibiotic plus steroid. Complications were similar in the two groups. No delay in healing rate of the ulcers was seen with the use of topical steroid. Two methods of assessing visual improvement are discussed, but it was not possible to demonstrate a difference in visual outcome between the two groups. PMID- 2203468 TI - Radioimmunoscintigraphy and immunohistochemistry with melanoma-associated monoclonal antibodies in choroidal melanoma: a comparison of the clinical and immunohistochemical results. AB - Radioimmunoscintigraphy with monoclonal antibodies (MoAbs) to melanoma associated antigens is a new technique that can be used as an additional test to detect ocular melanomas in clinically difficult cases. Immunoscintigraphy with 99mtechnetium-labelled monoclonal antibody fragments of MoAb 225.28S in 14 patients with melanoma yielded a positive image in only six cases (43%). The expression of high molecular weight melanoma-associated antigen (HMW-MAA) was immunohistochemically assessed in melanoma tissue obtained from these 14 patients to find a possible correlation between the results of immunoscintigraphy and expression of the HMW-MAA. The melanoma tissues were immunohistochemically stained by a sensitive immunoperoxidase procedure with three different monoclonal antibodies to the HMW-MAA: 225.28S, Mel-14, and AMF-6. Expression of the antigen detected by MoAb 225.28S was found in 13 of 14 melanomas; the MoAbMel-14 reacted positively with all 14 melanomas; staining with MoAb AMF-6 was achieved in 10 melanomas. No correlation was found between the immunohistochemical staining results, the conventional histopathological findings, and the immunoscintigraphic results. The immunohistochemical staining results suggest that anti-HMW-MAA MoAbs bind to the melanoma tissue and are therefore potentially suitable for immunoscintigraphy. PMID- 2203469 TI - Computerised visual field deficits in tears of the retinal pigment epithelium. AB - Retinal Pigment epithelial tears have been well documented as a complication of pigment epithelial detachment in patients with age related macular degeneration. Spontaneous and iatrogenic separation of detached retinal pigment epithelium, with subsequent retraction and exposure of the underlying choriocapillaris and Bruch's membrane, usually results in poor visual function in the affected areas. However, exact characterisation of the resultant scotomas has not been previously described. We present two patients with spontaneous pigment epithelial tears who underwent Octopus computerised visual field analysis. The density and characteristics of their associated field loss is compared with their clinical and fluorescein angiographic appearance. PMID- 2203470 TI - Management of intraocular melanoma. PMID- 2203471 TI - The lac permease of Escherichia coli: a prototypic energy-transducing membrane protein. PMID- 2203472 TI - The role of contact sites between inner and outer mitochondrial membrane in energy transfer. AB - Three functions have been suggested to be localized in contact sites between the inner and the outer membrane of mitochondria from mammalian cells: (i) transfer of energy from matrix to cytosol through the action of peripheral kinases; (ii) import of mitochondrial precursor proteins; and (iii) transfer of lipids between outer and inner membrane. In the contact site-related energy transfer a number of kinases localized in the periphery of the mitochondrion play a crucial role. Two examples of such kinases are relevant here: (i) hexokinase isoenzyme I which is capable of binding to the outer aspect of the outer membrane; and (ii) the mitochondrial isoenzyme of creatine kinase which is localized in the intermembrane space. Recently, evidence was presented that both hexokinase and creatine kinase are preferentially localized in contact sites (Adams, V. et al. (1989) Biochim. Biophys. Acta 981, 213-225). The aim of the present experiments was two-fold. First, to establish methods which enable the bioenergetic aspects of energy transfer mediated by kinases in contact sites to be measured. In these experiments emphasis was on hexokinase, while 31P-NMR was the major experimental technique. Second, we wanted to develop methods which can give insight into factors playing a role in the formation of contact sites involved in energy transfer. In the latter approach, mitochondrial creatine kinase was studied using monolayer techniques. PMID- 2203473 TI - Contact sites between inner and outer membranes: structure and role in protein translocation into the mitochondria. AB - Contact sites between both mitochondrial membranes play a predominant role in the transport of nuclear-coded precursor proteins into mitochondria. The characterization of contact sites was greatly advanced by the reversible accumulation of precursor proteins in transit (translocation intermediates). It was found that the sites are saturable, apparently contain proteinaceous components and mediate extensive unfolding of the polypeptide chain in translocation. Some components of mitochondrial contact sites are currently being identified. PMID- 2203474 TI - Thyroid hormone regulation of mitochondrial function. Comments on the mechanism of signal transduction. AB - Thyroid hormone exerts two types of effect on mitochondria. The first of these is a rapid activation of respiration which takes place within minutes after hormone injection, and is preserved in isolated mitochondria. The second response occurs after 1 to several days of injection and leads to mitochondrial biogenesis and increases in mitochondria mass. The hormone signal for these two responses involves either triiodothyronine (T3)-responsive nuclear genes or a direct action of T3 at mitochondria binding sites. PMID- 2203475 TI - The role of mitochondrial Ca2+ transport and matrix Ca2+ in signal transduction in mammalian tissues. AB - The pyruvate, NAD(+)-isocitrate and 2-oxoglutarate dehydrogenases are key regulatory enzymes in intramitochondrial oxidative metabolism in mammalian tissues, and can all be activated by increases in Ca2+ in the micromolar range. There is now mounting evidence that hormones and other stimuli which act by increasing cytosolic Ca2+ also, as a result, cause increases in mitochondrial matrix Ca2+ and hence activation of these enzymes, suggesting that the primary physiological function of mitochondrial Ca2(+)-transport is to be involved in this relay mechanism. This may also explain how in such circumstances rates of ATP production may be increased to meet the greater demand, but without any decreases in ATP/ADP occurring. PMID- 2203476 TI - Primary structure of the heparin-binding site of type V collagen. AB - The abilities of collagens, type I, II, III, IV, and V, to bind heparin were examined by heparin-affinity chromatography and binding studies with [35S]heparin. At a physiological pH and ionic strength, only type V collagen bound to heparin. Collagens type I and II showed higher affinities than types III and IV for heparin, but did not bind to a heparin column at a physiological ionic strength. The heparin binding site of type V collagen was located in a 30 kDa CNBr fragment of the alpha 1(V) chain, and the amino acid sequence of this fragment was determined. The 30 kDa fragment contained a cluster of basic amino acid residues, and enzymatic cleavage within this basic domain greatly reduced the heparin-binding activities of the resulting peptides. Thus this basic region is probably the heparin-binding site of type V collagen. PMID- 2203477 TI - Conversion of 5-aminoimidazole ribotide to the pyrimidine of thiamin in enterobacteria: study of the pathway with specifically labeled samples of riboside. AB - Samples of 5-amino-1-(beta-D-ribofuranosyl)imidazole labeled with 13C at position C-1 or C-2 of the ribose part or with 15N at position N-3 or amino of the imidazole part were prepared by chemical synthesis. The incorporation of label from these samples into the pyrimidine of thiamin biosynthesized by a mutant strain of Salmonella typhimurium was studied by GC-MS. The results show clearly that in enterobacteria the methyl carbon atom and the N-1 nitrogen atom of one molecule of thiamin pyrimidine derive from the same molecule of 5-aminoimidazole ribotide. More specifically, the methyl carbon atom comes from the carbon C-2' of the ribose part and the nitrogen N-1 from nitrogen N-3 of the imidazole; furthermore, the amino nitrogen of the aminoimidazole becomes the amino nitrogen of the pyrimidine. PMID- 2203478 TI - Cell size specific binding of the fluorescent dye calcofluor to budding yeast. AB - The yeast Saccharomyces cerevisiae cell surface outside of the bud scars displayed an increasing fluorescence intensity with increasing cell size (volume), where fluorescence was due to irreversible binding of the fluorescent dye calcofluor. The increase in fluorescence intensity appeared to be due to an increase in the density of fluorescence per unit surface area of the cell. Exposure time measurements from a photomicroscope were used to quantitate fluorescence intensity on individual cells. The cell size dependent increase in fluorescence intensity was displayed by unbudded cells from stationary phase populations, and unbudded and parent cells from exponentially growing populations. Abnormally large cells generated during the arrest of cell division with alpha-factor or restrictive temperature for cdc3, 8, 13, 24, and 28 cell division cycle mutants, displayed significantly greater fluorescence intensity compared to the smaller cells generated during the arrest of division for cdc25, 33, and 35 mutant strains. Fluorescence intensity on newly emerging buds was broadly dependent on both the size of the bud, and the size of the parent cells on which the buds were growing. PMID- 2203479 TI - [Hydrolysis of the isopeptide epsilon-(gamma-glutamyl)-lysine by destabilase from the medicinal leech Hirudo medicinalis]. AB - Using amino acid analysis, the ability of destabilize to hydrolyze the epsilon (gamma-Glu)-Lys isopeptide bond was demonstrated. Incubation of the epsilon (gamma-Glu)-Lys isopeptide with the enzyme was accompanied by a decrease of the amount of the isopeptide and an increase of equimolar amounts of lysine and glutamic acid. Complete hydrolysis of the isopeptide was observed after 96 hour incubation with destabilize. It was supposed that the isopeptide is a less specific substrate for destabilize compared to L-gamma-Glu-pNA. PMID- 2203480 TI - Exogenous insulin and additional energy affect follicular distribution, follicular steroid concentrations, and granulosa cell human chorionic gonadotropin binding in swine. AB - The objective was to determine whether exogenous insulin and dietary energy interact to affect follicular development in gilts. In a 2 x 2 x 2 completely randomized design, main effects were level of dietary energy (5771 or 9960 kcal metabolizable energy/day beginning on Day 12 of the estrous cycle), insulin dosage (0 or 0.4 IU/kg twice daily beginning on Day 15 of the cycle), and day of cycle at ovary removal (Day 17 or Day 19). Percentage of follicles designated small (less than or equal to 3 mm diameter) decreased from Day 17 to Day 19 of the cycle, and the percentage of large follicles (greater than or equal to 7 mm) increased (p less than 0.05). Insulin interacted with day of the cycle (p less than 0.05) to affect distribution of medium (4-6 mm) and macroscopically atretic follicles. Percentage of atretic follicles increased from Day 17 to Day 19 in saline-treated (from 15.5% to 38.2%) but not in insulin-treated animals (6.3% to 10.7%). Percentage of medium (4-6 mm) follicles decreased from Day 17 to Day 19 in saline-treated gilts (from 41.7 to 16.6%) but not in insulin-treated gilts (39.8% to 35.1%). Intrafollicular testosterone and progesterone concentrations were not affected by treatments. In medium follicles, the ratio of estradiol to progesterone was greater (p less than 0.05) for insulin-treated gilts on Day 17 than for the other treatment combinations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203482 TI - Platelet immunoglobulin G: its significance for the evaluation of thrombocytopenia and for understanding the origin of alpha-granule proteins. PMID- 2203481 TI - What role for prednisone in prevention of acute graft-versus-host disease in patients undergoing marrow transplants? AB - One hundred forty-seven consecutive patients with leukemia, myelodysplastic syndrome, or aplastic anemia were treated by marrow grafts from genotypically HLA identical siblings (n = 122) or HLA-haploidentical family members (n = 25). Haploidentical recipients differed from their donors for no more than one HLA locus on the nonshared haplotype. All were given postgrafting immunosuppression with a combination of methotrexate and cyclosporine. In a randomized study we explored whether prednisone administered from day 0 through 35 along with methotrexate/cyclosporine could improve prevention of acute graft-versus-host disease (GVHD). The GVHD incidence in patients not given prednisone was comparable with that previously reported with methotrexate/cyclosporine. Unexpectedly, significant increases in acute and also chronic GVHD were seen in HLA-identical recipients administered prednisone, but not in the small number of patients administered HLA-nonidentical grafts. However, the resultant increase in transplant-related mortality in patients administered prednisone was offset by an increase in leukemic relapse in patients not administered prednisone, presumably related to the absence of a graft-versus-leukemia effect. Therefore, overall disease-free survival of the two groups of patients was comparable, with slightly more than 50% of the patients being alive at more than 2 years after transplantation. We speculated that prednisone adversely affected GVHD prophylaxis, interfering with methotrexate's cell cycle-dependent suppression of donor lymphocyte proliferation in response to host antigens. In a pilot study we explored whether beginning prednisone on day 15, after completion of methotrexate administration, would avoid this adverse effect. The GVHD incidence in patients administered methotrexate/cyclosporine along with "late" prednisone was comparable with that in patients not administered prednisone. We conclude that methotrexate/cyclosporine is effective in decreasing the incidence of grade II through IV GVHD, and that the addition of prednisone to this regimen is not beneficial in recipients of HLA-identical marrow grafts. PMID- 2203483 TI - Endometriosis. PMID- 2203484 TI - Warning leak in subarachnoid haemorrhage. PMID- 2203485 TI - Colles' fracture. PMID- 2203486 TI - Prolonged blood pressure reduction by orally active renin inhibitor RO 42-5892 in essential hypertension. AB - OBJECTIVE: To investigate the effects of a novel specific renin inhibitor, RO 42 5892, with high affinity for human renin (Ki = 0.5 x 10(-9) mol/l), on plasma renin activity and angiotensin II concentration and on 24 hour ambulatory blood pressure in essential hypertension. DESIGN: Exploratory study in which active treatment was preceded by placebo. SETTING: Inpatient unit of teaching hospital. PATIENTS: Nine men with uncomplicated essential hypertension who had a normal sodium intake. INTERVENTIONS: Two single intravenous doses of RO 42-5892 (100 and 1,000 micrograms/kg in 10 minutes) given to six patients and one single oral dose (600 mg) given to the three others as well as to three of the patients who also received the two intravenous doses. RESULTS: With both intravenous and oral doses renin activity fell in 10 minutes to undetectably low values, while angiotensin II concentration fell overall by 80-90% with intravenous dosing and by 30-40% after the oral dose. Angiotensin II concentration was back to baseline four hours after the low and six hours after the high intravenous dose and remained low for at least eight hours after the oral dose. Blood pressure fell rapidly both after low and high intravenous doses and after the oral dose and remained low for hours. With the high intravenous dose the daytime (0900-2230), night time (2300 0600), and next morning (0630-0830) systolic blood pressures were significantly (p less than 0.05) lowered by 12.5 (95% confidence interval 5.6 to 19.7), 12.2 (5.4 to 19.3), and 10.7 (3.2 to 18.5) mm Hg respectively, and daytime diastolic pressure was lowered by 9.3 (2.2 to 16.8) mmHg. With the oral dose daytime, night time, and next morning systolic blood pressures were lowered by 10.3 (5.5 to 15.4), 10.5 (4.2 to 17.2), and 9.7 (4.0 to 15.6) mm Hg, and daytime and night time diastolic pressures were lowered by 5.8 (0.9 to 11.0) and 6.0 (0.3-12) mm Hg respectively. CONCLUSIONS: The effect of the inhibitor on blood pressure was maintained over a longer period than its effect on angiotensin II. RO 42-5892 is orally active and has a prolonged antihypertensive effect in patients who did not have sodium depletion. This prolonged effect seems to be independent, at least in part, of the suppression of circulating angiotensin II. PMID- 2203487 TI - Ultrasonography compared with intravenous urography in investigation of urinary tract infection in adults. AB - OBJECTIVE: To compare ultrasonography with intravenous urography for investigating adults with proved urinary tract infection. DESIGN: Prospective study of patients presenting consecutively for radiological investigation of urinary tract infection between October 1988 and December 1989. Both investigations were performed concurrently and performed independently on routine lists by different duty radiologists, each of whom knew the details on the request form but not the findings of the other investigation. SETTING: Radiology department of a teaching hospital. PATIENTS: 158 Consecutive adults (89 women, 69 men; mean age 49.7 (range 18-83)) referred from general practitioners and hospital outpatient clinics with a history of proved urinary tract infection. INTERVENTIONS: Urography and ultrasonography performed concurrently. When both examinations gave normal findings no clinical or radiological follow up was sought. All abnormal findings detected with either investigation were confirmed by subsequent imaging studies or by operative procedures. MAIN OUTCOME MEASURE: Accuracy of detection of abnormalities of urinary system by ultrasonography compared with urography. RESULTS: 113 Patients (72%) had normal urographic and ultrasonic findings. Overall, ultrasonography concurred with the findings of urography in 149 (94%) patients, and when a single abdominal radiograph was included in the procedure, in 152 (96%). Ultrasonography missed only one important diagnosis, that of mild papillary necrosis in normal sized kidneys in a diabetic patient. It detected one early bladder tumour not visible on urography and was able to clarify the nature of renal masses (simple cysts) evident on three urograms. CONCLUSION: Ultrasonography provides a safe and accurate method of imaging the urinary tract in adults with infection. Combined with a plain abdominal radiograph, it should replace urography as the initial imaging investigation in these patients. Major savings would result from adopting this policy, and the risks to patients from ionising radiation and intravenous contrast media would be appreciably reduced. PMID- 2203488 TI - Cerebral mass lesions in patients with AIDS. PMID- 2203489 TI - ABC of major trauma. Management of limb injuries. PMID- 2203490 TI - Symptomatic carotid ischaemic events. PMID- 2203491 TI - Cell implantation in Parkinson's disease. PMID- 2203492 TI - Extracorporeal membrane oxygenation. PMID- 2203494 TI - Activities of aminotransferases after treatment with streptokinase for acute myocardial infarction. PMID- 2203495 TI - ABC of major trauma. Paediatric trauma: primary survey and resuscitation--I. PMID- 2203493 TI - Management of isolated thyroid swellings: a prospective six year study of fine needle aspiration cytology in diagnosis. AB - OBJECTIVE: To audit the accuracy and impact on the frequency of operation of fine needle aspiration cytology of isolated thyroid swellings. DESIGN: Prospective analysis over six years of cytological predictions compared with histological findings. SETTING: Thyroid clinic serving the Grampian region. PATIENTS: 395 Consecutive patients presenting with an isolated thyroid swelling, 307 of whom underwent surgical excision. Analysis was confined to a subgroup of 283 patients with satisfactory aspirates who were operated on. RESULTS: The positive predictive value of aspiration cytology for detecting malignant disease was 100% and the sensitivity 83%. The sensitivity for the detection of neoplasia (frank malignancy together with follicular adenomas) was 76%. The specificity was 58% and the overall accuracy 69%. Recalculation of data in previous papers with strict criteria showed the accuracy of aspiration cytology to be variable and lower than is widely accepted. Since the introduction of aspiration cytology 21% fewer operations for isolated thyroid swellings have been performed. CONCLUSIONS: As a basis of selection for surgical excision of isolated thyroid swellings according to prediction of neoplasia fine needle aspiration cytology is less reliable than is widely accepted. It is an adjunct to management rather than a definitive test, and negative cytological results do not exclude neoplastic disease. Further study should take account of the implications of repeated clinic attendances for review and aspiration as these may culminate in delayed surgical treatment. PMID- 2203496 TI - Journal pricing issues: an economic perspective. AB - Scientific journal prices have increased markedly in the past two decades, outpacing inflation by severalfold. Such increases challenge the librarian's ability to manage acquisitions resources effectively and threaten the mission of the health sciences library as a resource for present and future scientific information needs. Explanations for serial price increases vary with the point of view considered. Publishers, librarians, faculty, and consumers of scientific information perceive the situation differently. This paper provides an economic analysis of each group's views. Particular emphasis is given to the aspects of journal publishing and pricing that foster price increases. In addition, the paper examines the problems of dual-pricing structures and narrowly focused journals that cater to subspecialties of medicine. Suggested responses to subscription rate increases are offered to curtail further increases and to avoid the potential detrimental effects of reduced library collections. Since one of the underpinnings of education is threatened by reductions in library collections, actions must be taken by publishers, librarians, faculty, and professional associations to ameliorate the present situation and to limit additional increases in serial prices. PMID- 2203497 TI - CD-ROM MEDLINE use and users: information transfer in the clinical setting. AB - Effective delivery of biomedical information to health professionals depends on the availability of systems that are compatible with the information-seeking patterns of health professionals. MEDLINE is a major source of biomedical information, but has been available primarily through libraries via telecommunications networks. The recent availability of MEDLINE on CD-ROM has made it possible to provide MEDLINE directly to clinicians without the associated problems of telecommunications and online use charges. The MEDLINE on CD-ROM Evaluation Forum sponsored by the National Library of Medicine reported on clinicians' use of CD-ROM MEDLINE at seven different clinical settings. This article summarizes the findings from these sites and places them in the context of current understanding of information-seeking behaviors of health professionals. Key issues in the design and development of information technologies in the clinical setting are also articulated. PMID- 2203498 TI - Monitoring patron use of CD-ROM databases using SignIn-Stat. AB - SignIn-Stat, a PC-based, menu-driven program, collects information from users of the library's public access computer systems. It was used to collect patron use data for the library's four CD-ROM workstations for the period September 1987 to April 1988 and to survey users for the period December 1987 to March 1988. During the sample period, 5,909 CD-ROM uses were recorded. MEDLINE was the most heavily used database, followed by PsycLIT and Micromedex CCIS. Students accounted for 61% of the use, while faculty, residents, and staff were responsible for 31%. Graduate students had the highest rate of use per student. Nineteen percent of use was by patrons who had never used CD-ROMs before, while 37% was by patrons who had used CD-ROMs ten or more times. Residents were the least experienced user group, while graduate students and faculty were the most experienced. PMID- 2203499 TI - Knowledge bases in medicine: a review. AB - Efforts to represent knowledge effectively have been central to progress in various aspects of medical informatics. These efforts range from relatively simple "electronic textbooks" to fairly sophisticated knowledge-based systems, which function as well as, or even better than, human experts faced with similar problems. Knowledge bases have been developed in many fields, but the relatively limited domains and structured language of medicine, as well as the importance of information in the provision of good medical care, have made research in medical knowledge representation an area of intense activity. This paper reviews representative knowledge bases and knowledge-based systems in medicine: electronic textbooks such as PDQ and the Hepatitis Knowledge Base (HKB), rule based systems such as MYCIN, causal models (e.g., CASNET), and hypothesis- or frame-based systems, exemplified by PIP and INTERNIST-1. The paper describes the relationships among divergent approaches and provides a sense of current and future trends. It examines problems in knowledge-based systems, particularly in knowledge representation and acquisition, and the responses to these challenges. The latter include the use of domain-independent software shells for constructing knowledge bases, the adaptation and use of previously existing knowledge bases, and multiple uses of the same knowledge base for different purposes. PMID- 2203500 TI - Lucretia W. McClure. Medical Library Association President 1990-1991. PMID- 2203501 TI - Clinical significance of the antibody-coated bacteria test in patients with candiduria. AB - The clinical significance of the antibody-coated bacteria (ACB) test was evaluated with urine from 20 patients with candiduria. The relationship between the in vitro antibody-coating test for Candida albicans, urinary immunoglobulin (Ig) levels and serum antibody titres was evaluated in 40 patients without candiduria, 23 of whom had bacterial urinary tract infection (UTI). Urine specimens from 19 of the 20 patients with candiduria gave a positive result regardless of clinical symptoms; 12/23 specimens of urine from patients with bacterial UTI were positive for antibody-coated C. albicans cells, but there were no positive samples in the patients without UTI. All of the coating-positive patients had serum antibody titres greater than or equal to 1:160, the class of antibody being dependent on the urinary Ig levels. The ACB test for candiduria is of little clinical value in indicating invasive Candida UTI as the Candida cells appear to adhere to antibodies in urine contaminated with circulating fluids. PMID- 2203502 TI - Pathogenesis of chronic bacterial prostatitis in an animal model. AB - A reproducible rat model of chronic bacterial prostatitis was developed using a defined bacterial pathogen (Escherichia coli) to study the pathogenesis and persistence of chronic bacterial prostatitis. The progression of inflammation and its consequences from acute to chronic prostatitis were documented with microbiological, histological, ultrastructural and immunological data. Chronic bacterial prostatitis in this model was associated with sparse glycocalix enclosed protected bacterial microcolonies within the prostatic acini and ducts which appeared to stimulate a persistent local and systemic immunological reaction resulting in chronic inflammation of the gland. This model has many striking similarities to the natural history of human chronic bacterial prostatitis. PMID- 2203503 TI - Prostatic cancer with bone metastases: serum alkaline phosphatase (SAP) as a predictor of response and the significance of the SAP "flare". AB - The predictive value of serum alkaline phosphatase (SAP) and of prostatic acid phosphatase (PAP) for response to treatment (NPCP criteria) was retrospectively assessed in patients with bone metastases from prostate cancer. Fifty-one patients had SAP measured at the start of treatment and at 1 and 2 months. In 31 of these, corresponding PAP levels were also available at each time point. SAP/PAP profiles at 2 months were classified as "increased" (increment 15% or greater), "decreased" (reduction greater than 15%) or "stable", compared with baseline levels. An additional category, SAP "flare", was also identified (SAP increment greater than 15% at 1 month, with subsequent fall at 2 months). There was a strong association between the SAP profile at 2 months and the response category, whereas the PAP profile at 2 months was more weakly associated. Using results from the 31 patients with both SAP and PAP profiles, the level of SAP was significantly better in predicting the category of response (SAP: sensitivity 94%, specificity 79%; PAP: sensitivity 53%, specificity 57%). An SAP "flare" was associated with response in 8 of 12 patients. An increase in SAP at 1 month is therefore a poor guide to progressive disease and should not be used in isolation to discontinue treatment early. The SAP profile is of value as an earlier predictor of response than X-rays or bone scans and is more reliable than the PAP profile in monitoring patients with prostate cancer and bone metastases. PMID- 2203504 TI - Amoebic liver abscess. PMID- 2203505 TI - Surgical therapy of oesophageal carcinoma. AB - During the past 10 years, postoperative mortality associated with surgical treatment of oesophageal carcinoma has been reduced by one-half. However, it appears that all efforts to improve long-term survival with extensive excisional procedures and adjuvant chemotherapy and radiotherapy have failed. Fifty-six of 100 patients presenting to the surgeon with an oesophageal carcinoma have resectable disease. Recent studies suggest that seven of them will die from postoperative complications and 49 patients will be discharged from the hospital after an average of 3 weeks. Of these patients, 27 will survive the first, 12 the second, and ten the fifth year. Although it may be possible to further reduce postoperative complications and mortality, the chances of improving the long-term prognosis of patients with oesophageal carcinoma seem small. PMID- 2203506 TI - Surgical pathology of HIV infection: lessons from Africa. AB - Human immunodeficiency virus has resulted in a major change in the presentation and behaviour of certain common diseases in Africa. This review describes some of the important changes and discusses the implications for management. PMID- 2203507 TI - Colon wound management and prograde colonic lavage in large bowel trauma. AB - Between 1983 and 1987 prograde colonic lavage was prospectively evaluated in 389 patients with colon trauma. Predefined high risk patients had exteriorization of the primarily sutured colon. Intraperitoneal primary closure was otherwise used. Patients received prograde colonic lavage by random allocation. The healing exteriorized colon was interiorized 5-10 days after the initial surgery. The median age was 29 years and only 28 patients were women. Injuries were due to stab (316), gunshot (54), shotgun (10) or blunt trauma (9). Exteriorization of the primarily sutured colon was carried out in 217 patients of whom 101 had prograde colonic lavage. Twenty (9 per cent) died. Of the survivors, 150 (76 per cent) had their colon successfully interiorized and this rate was unaffected by prograde colonic lavage. Intraperitoneal primary closure was performed in 172 patients of whom 91 had prograde colonic lavage. Seven (4 per cent) died. Mortality was directly related to the number of associated injuries. Prograde colonic lavage, irrespective of the type of colonic wound management used, did not reduce the mortality rate, which was 7.2 per cent for those who had such lavage and 6.6 per cent for the rest. Prograde colonic lavage cannot therefore be recommended in colon trauma. PMID- 2203508 TI - Endorectal ultrasonography for the assessment of invasion of rectal tumours and lymph node involvement. AB - Sophisticated therapies for rectal carcinoma, such as sphincter preserving operations, pouch-anal anastomosis, preoperative irradiation or adjuvant chemotherapy, require an exact pretherapy assessment of the tumour and its lymph node involvement. A 7.0 MHz transducer was used before operation in the staging of 117 patients with rectal carcinoma or villous adenoma. In 90 per cent of cases it was possible correctly to stage the tumour before operation. Sensitivity for detection of perirectal fat infiltration was 97 per cent. Lymph node involvement was accurately identified in about 80 per cent of cases. Six carcinomas, which had developed within 31 examined tubulovillous adenomas, were detected by endorectal ultrasonography. No carcinoma remained undetected. Endorectal ultrasonography is a highly accurate tool for the staging of rectal carcinoma before operation and for the detection of lymph node involvement. Malignant change in tubulovillous adenomas are also detectable. PMID- 2203509 TI - The historic development of cryosurgery. PMID- 2203510 TI - Cryosurgery: complications and contraindications. PMID- 2203511 TI - Immunologic aspects of cryosurgery: potential modulation of immune recognition and effector cell maturation. PMID- 2203512 TI - Cryosurgical instrumentation and depth dose monitoring. PMID- 2203513 TI - Ultrasound in cryosurgery. PMID- 2203514 TI - Treatment of cryosurgery in the premalignant and benign lesions of the skin. PMID- 2203515 TI - Cryosurgery in the treatment of skin cancers: indications and management. PMID- 2203516 TI - Hormonal therapy of prostatic carcinoma. Defining the challenge. AB - Prostate cancer is the most common neoplasm in the American male. More than 50% of patients present with locally advanced or metastatic disease and are not curable with local therapies such as radical prostatectomy or radiation therapy. This cancer is hormonally dependent, and methods that interrupt the hypothalamus pituitary-testicular axis have been used to treat and control the disease effectively. The role of neutralizing the adrenal androgens is controversial. Combined androgen blockade refers to treatment modalities that lower circulating serum testosterone such as bilateral orchiectomy or an LH-RH agonist and combining it with an antiandrogen. The issue at hand is to review current clinical trials addressing the concept of combined androgen blockade and to determine the feasibility of a meta-analysis. PMID- 2203517 TI - A controlled trial of castration with and without nilutamide in metastatic prostatic carcinoma. AB - A randomized double-blind trial in patients with disseminated, previously untreated prostate cancer (Stage D2) was conducted in eight Canadian centers. All 203 patients enrolled in this study underwent bilateral orchiectomy and were randomized to receive either the nonsteroidal anti-androgen nilutamide or a placebo. Patient responses were graded according to the criteria of the National Prostatic Cancer Project (NPCP). Patients treated with nilutamide had a significantly greater number of positive objective responses (partial and complete regression) than did the patients treated with castration alone (46% versus 20%, P = 0.001). Progression-free survival was improved initially in the nilutamide group, but the median time to progression was 12 months for both groups. Despite an increase in the median length of survival from 18.9 to 24.3 months with the nilutamide, the survival time was not significantly longer in the nilutamide group (log = rank test, P = 0.048). Although minor side effects were frequent, adverse effects related to the medication and leading to discontinuation of treatment were observed in 9% of cases. These results suggest some benefit of the combined treatment (orchiectomy + nilutamide) over orchiectomy alone in the treatment of metastatic prostatic carcinoma. PMID- 2203518 TI - Complete androgen blockade in prostate cancer. Organizing an overview. AB - The value of the addition of a pure antiandrogen to castration in advanced prostate cancer will be evaluated by an overview of all randomized studies addressing this question. This overview is currently being organized. Care is taken on identifying all randomized studies, published or unpublished, to avoid publication bias. Already 15 studies possibly related to the question are under investigation. Principal investigators of each relevant study are invited to participate in the overview. The principal end points of the study are overall and cause-specific mortality. The first report of results is planned for the end of 1991. PMID- 2203519 TI - Prospective new developments in laboratory research and clinical trials in prostatic cancer. AB - Laboratory research continues to develop new methods supporting clinicians in the management of prostatic cancer. Routine measurements of serum prostate-specific antigen (PSA) levels improve diagnosis, provide insight into tumor burden, and sharpen prognostication. New organ-specific antigenic targets are identified for monoclonal antibody-directed diagnostic and radiotherapeutic reagents. Such new immunospecific conjugates are already under evaluation in clinical trials. Cell culture techniques carry the promise of noninvasive early detection and prognostic evaluation of prostatic malignancy in preclinical stages. Molecular mechanisms responsible for androgen regulation of proliferation and malignancy of prostatic cancer are becoming open for scientific inquiry. PMID- 2203520 TI - Combined castration and androgen blockade therapy in prostate cancer. Conclusions. PMID- 2203521 TI - Analysis of dietary fat, calories, body weight, and the development of mammary tumors in rats and mice: a review. AB - We have extracted from the literature data from 100 animal experiments, involving 7838 rats and mice, which compared the effects of different levels of dietary fat and/or calorie intake on the development of mammary tumors. Both higher calorie intake (P less than 0.0001) and higher fat intake (P less than 0.0001) independently increased mammary tumor incidence in Sprague-Dawley rats and in mice, as judged from analyses combining ad libitum feeding experiments and restricted feeding experiments. The effect of fat was two thirds the magnitude of the calorie effect in both Sprague-Dawley rats and mice. In ad libitum feeding experiments, a modest but significant (P less than 0.0001) average increase in body weight was found in animals fed high fat diets. However, these differences in body weight did not correspond to differences in mammary tumor incidence. The effect of log body weight on the log odds of tumor incidence was not significant (P = 0.16), while dietary fat intake significantly increased tumor incidence (P less than 0.0001). The collection of animal experimental data supports the hypothesis that, in mammary tumor development, there is a specific enhancing effect of dietary fat, as well as a general enhancing effect of calories. PMID- 2203522 TI - Constitutive and induced expression of growth factors in normal and chronic phase chronic myelogenous leukemia Ph1 bone marrow stroma. AB - Study of growth factor RNA levels in the stromal cells derived from the adherent layer of long-term bone marrow culture demonstrated constitutive expression of transforming growth factor beta 1 (TGF-beta 1) and macrophage colony-stimulating factor. These cells did not express granulocyte colony-stimulating factor, granulocyte-monocyte colony-stimulating factor, interleukin (IL) 1 alpha, IL-1 beta, IL-3, and IL-6. However, granulocyte colony-stimulating factor expression could be induced by recombinant human IL-1 beta; while IL-6 could be induced by both IL-1 beta and tumor necrosis factor-alpha. No differences could be detected between adherent layers established from normal and benign phase Ph1 chronic myelogenous leukemia bone marrow. The uninduced expression of TGF-beta 1, a potent hematopoietic cell growth inhibitor, suggests that stromal cells play an inherent role in regulating the proliferation of adjacent bone marrow hematopoietic progenitor cells. However, a defect in stromal TGF-beta 1 production cannot account for the profoundly expanded myeloid compartment in chronic phase chronic myelogenous leukemia. In contrast to the constitutive expression of TGF-beta 1 and macrophage colony-stimulating factor, hematopoietic growth factors are only expressed following a proper stimulation. PMID- 2203523 TI - Isolation of a human melanoma adapted Newcastle disease virus mutant with highly selective replication patterns. AB - The apathogenic Newcastle disease virus (NDV) strain Ulster has been used successfully as an adjuvant component for active specific immunotherapy of malignant mouse lymphoma, and in nude mice it was shown to be able to lead to retardation of the s.c. growth of xenotransplanted human melanoma cells. In order to improve in vivo effectiveness of virotherapy of human tumors without significantly increasing the risk of unspecific viral replication in host cells, we adapted the virus for growth in a human melanoma line (MeWo M). For this purpose NDV Ulster was mutagenized and a variant was selected which could replicate and reinfect the tumor line. The mutant (NDV 1E 10) performed late lysis on the melanoma line. Replication was found to be at least 100 times more efficient in MeWo M than in 6 of 8 other human tumor cell lines of different tissue origin. In 10 of 11 murine cell lines, NDV 1E 10 did not replicate via multicycles. Chick embryonic fibroblasts were permissive for nonlytic replication. Neither the virulent wild-type NDV Italian nor the avirulent strain NDV Ulster shared these specific replication properties with the new variant. We also established MeWo melanoma sublines with different metastatic capacities and tested them as targets for NDV 1E 10 infection. The MeWo subpopulations exhibited comparatively small differences in permissivity for multicyclic replication, but the more metastatic MeWo Met, like allogeneic melanoma lines, was more resistant to lysis. NDV Italian, in contrast, showed no differences in replication and lysis on any of the tested melanoma lines. Trypsin-activation experiments suggested an incomplete cleavage of mutant envelope glycoprotein F by the permissive cell line and, thus, mechanisms of specific infection and replication not requiring fully activated envelope glycoproteins. PMID- 2203524 TI - Morphological and molecular characterization of spontaneous myogenic differentiation in a human rhabdomyosarcoma cell line. AB - Skeletal muscle differentiation consists of an ordered withdrawal of committed cells from the cell cycle and their fusion to form multinucleated myotubes. To determine if differentiation of malignant myoblasts parallels that of normal skeletal muscle, a cell line (Rh28) was established from an alveolar rhabdomyosarcoma. Rh28 displays a constant population doubling time of 45-55 h until passage 60, when the doubling time progressively increases until proliferation ceases. Loss of proliferative capacity is associated with morphological evidence of differentiation to multinucleated myotubes, fusion, and the expression of numerous muscle-specific genes. In contrast to normal myogenic differentiation, multinucleated cells continue to synthesize DNA and express abundant c-myc transcripts. These observations suggest synchronous replication and possible arrest in the G2-phase of the cell cycle, since there was no evidence of mitotic activity in differentiated cells. Terminal differentiation of early passage Rh28 cells was induced in the presence of 10% dialyzed fetal calf serum but not by medium containing 2% undialyzed serum, suggesting a role for low molecular weight growth factors in this process. Our data indicate that the Rh28 cell line may be of value in elucidating the relationship between oncogenic transformation and differentiation in rhabdomyosarcoma. PMID- 2203525 TI - Transfection of activated Ha-ras protooncogenes causes mouse mammary hyperplasia. AB - ras protooncogenes activated by a point mutation have been implicated in the initiation of mammary carcinogenesis. However, the nature of phenotypic alterations induced by activated ras protoonocogenes during initiation has not been well understood. In the present studies, the phenotypic manifestation of activated ras genes was directly analyzed by transfecting them into normal mouse mammary epithelial cells. The ras genes were cotransfected with pSV2neo which expresses the bacterial neomycin resistance gene to partially select for successful transfectants in culture. Transfection of activated Ha-ras protooncogenes, containing a point mutation in codon 12, caused hyperplasia in the mouse mammary gland following transplantation. Hyperplastic phenotype is a prerequisite for neoplastic development. The hyperplasias induced by the activated Ha-ras protooncogenes, however, were not immortal in vivo, another essential characteristic of preneoplastic and neoplastic mouse mammary cells. Control cells transfected only with pSV2neo did not produce any hyperplasia. These results suggest that a functional role of activated ras protooncogenes in the initiation of mouse mammary carcinogenesis may be the induction of a hyperplastic phenotype, a prelude to neoplastic development. PMID- 2203526 TI - [An unknown contribution to the autobiography of Jan Evangelista Purkinje]. PMID- 2203527 TI - [Immunopathogenetic concepts of HIV infection]. PMID- 2203528 TI - [Changes in the use of biologically effective fluorides and the consequences]. AB - The nearly 50-year dispute about the usefulness of public water supply fluoridation is basically a dispute about whether the human consumer can be given "optimum" doses of fluorides even in some communities with markedly less than 1 mg/1 F in drinking water. At the very beginning of this dispute, some basically conflicting epidemiological data were found (only seemingly so in our view): around the year 1940 the rate of dental caries in USA children dropped precipitously on drinking water with fluoride concentration growing at an interval of 0.1-0.5 mg/l; at higher concentrations the dental caries rate was declining increasingly less and less (and at concentrations of over 2 mg/l it began picking up again). In contrast to this, in the Federal Republic of Germany in 1950, the interval of 0.1-0.5 mg/l F was related to absolutely no decline in the dental caries rate which was practically as low as in the United States on drinking water containing 2 mg/l. These and other "contradictory" data are put down to man's different intake of fluorides coming from sources other than water. The main cause of different intakes of fluorides from food is apparently in the degree of intensity of field fertilisation with phosphates containing a marked proportion of fluorine, in other words, different intensity of agricultural land fluoridation. In Germany, 23 kg of P2O5 per hectare of arable land was used as early as in 1935, while in the United States this intensity was not reached until 1985.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203529 TI - [Unidentified Masonic memorabilia from the estate of J.E. Purkinje]. PMID- 2203530 TI - Glucose induces temperature-dependent oscillations of cytoplasmic Ca2+ in single pancreatic beta-cells related to their electrical activity. AB - Glucose induces large amplitude oscillations of the cytoplasmic Ca2+ concentration ([Ca2+]i) in pancreatic beta-cells. The effects of temperature on these oscillations were examined by monitoring [Ca2+]i continuously in single beta-cells from ob/ob-mice using dual wavelength microfluorometry. The oscillations of [Ca2+]i disappeared when the temperature was increased above 42 degrees C and were reversibly inhibited below 30 degrees C. However, cooling did not prevent a glucose response in terms of the average rise of [Ca2+]i. Since patch clamp studies of single beta-cells have indicated a random occurrence of glucose-induced action potentials at room temperature, it was important to explore how the sugar affected the electrical activity at 37 degrees C. Using the cell-attached configuration of the patch clamp technique for such analyses, the action potentials were found to occur in bursts with durations similar to the large amplitude oscillations of [Ca2+]i. PMID- 2203531 TI - The DNA binding subunit of NF-kappa B is identical to factor KBF1 and homologous to the rel oncogene product. AB - The major determinant in the transcriptional control of class I genes of the major histocompatibility complex is an enhancer sequence located around -170 from the transcription start site, which binds a factor named KBF1. We have isolated a complementary cDNA coding for KBF1 and identified the DNA binding and dimerization domain of the protein. Because KBF1 and the transcription factor NF kappa B bind to similar sequences, we investigated the relationship between these two molecules. It appeared that KBF1 is, by all criteria used, identical to the 50 kd DNA binding subunit of NF-kappa B. KBF1 (and therefore p50) also displays extensive amino acid sequence homology with the v-rel oncogene and the Drosophila maternal morphogen dorsal. In vitro experiments suggest functional homologies between KBF1 and v-rel. PMID- 2203532 TI - Cloning of the p50 DNA binding subunit of NF-kappa B: homology to rel and dorsal. AB - The DNA binding subunit of the transcription factor NF-kappa B, p50, has been cloned. p50 appears to be synthesized as a larger protein that is then processed to its functional size. Sequence analysis reveals remarkable homology for over 300 amino acids at the amino-terminal end to the oncogene v-rel, its cellular homolog c-rel, and the Drosophila maternal effect gene dorsal. This establishes NF-kappa B as a member of the rel family of proteins, all of which display nuclear-cytosolic translocation. Protein sequence from the p65 polypeptide has established that it is not encoded in the same mRNA as p50. However, p65 appears homologous to c-rel, suggesting that c-rel may form heterodimers with p50 and rel may include a homodimerization motif. PMID- 2203533 TI - NF-kappa B, KBF1, dorsal, and related matters. PMID- 2203534 TI - The two faces of higher eukaryotic DNA replication origins. PMID- 2203535 TI - Maize R gene family: tissue-specific helix-loop-helix proteins. PMID- 2203536 TI - A cdc2-like protein is involved in the initiation of DNA replication in Xenopus egg extracts. AB - Extracts of Xenopus eggs efficiently initiate and complete chromosomal DNA replication in vitro, under normal cell cycle controls. Such extracts can be depleted of Xenopus p34cdc2, either by affinity depletion using the protein p13suc1 or by specific immunodepletion. Depleted extracts are incapable of initiating DNA replication, although they efficiently elongate replication forks initiated in undepleted extracts. Depletion of p34cdc2 does not prevent nuclear assembly, which is required for the initiation of DNA replication in this system. Activity can be restored to depleted extracts by readdition of p13suc1 eluates enriched for p34cdc2. These results demonstrate that p34cdc2, or a very closely related protein, is involved in the initiation of chromosomal DNA replication in the cell cycle of higher eukaryotes. PMID- 2203537 TI - The fission yeast cut1+ gene regulates spindle pole body duplication and has homology to the budding yeast ESP1 gene. AB - Mutations in the fission yeast cut1+, cut2+, and cut10+ genes uncouple normally coordinated mitotic events and deregulate, rather than arrest, mitosis. DNA synthesis continues, making polyploid nuclei with several spindles. Multiple, aberrant spindle pole bodies (SPBs) are produced in cut1 mutant cells. The cut1+ and cut2+ genes are cloned by transformation. High gene dosage of cut1+ also complements cut2 and cut10 mutants. The cut2+ gene, however, complements only cut2. The 210 kd cut1+ gene product contains putative ATP binding and helical coil regions followed by a COOH-terminal domain homologous to the S. cerevisiae gene ESP1. Mutations in the ESP1 gene also result in many SPBs. The cut1+ product is shown by anti-cut1 antibody to be a rare component of the insoluble nuclear fraction. It may play a key role in coupling chromosome disjunction with other cell cycle events and is potentially a component, regulator, or motor for the SPB and/or kinetochores. PMID- 2203538 TI - Meiotic gene conversion and crossing over: their relationship to each other and to chromosome synapsis and segregation. AB - The yeast mer1 mutant produces inviable spores and is defective in both meiotic recombination and chromosome pairing. A gene called MER2 partially suppresses the mer1 phenotype when present in high copy number. Both gene conversion and chromosome pairing are completely restored in mer1 strains overexpressing MER2; however, reciprocal crossing over and spore viability are not restored. The data presented are consistent with a model in which chromosome pairing is a direct consequence of a homology search mediated through gene conversion. Analysis of random viable spores indicates that the crossovers that occur in mer1 strains overexpressing MER2 are more effective in ensuring meiosis I disjunction than those that occur in mer1 strains. One interpretation of this result is that only those crossovers that occur in the context of the synaptonemal complex lead to the establishment of functional chiasmata. The MER2 gene product is essential for meiosis. PMID- 2203539 TI - The E. coli dnaK gene product, the hsp70 homolog, can reactivate heat-inactivated RNA polymerase in an ATP hydrolysis-dependent manner. AB - Pelham previously proposed that the hsp70 family of heat shock proteins could prevent the formation and/or allow the dissolution of protein aggregates created during stress conditions. We confirmed this hypothesis by showing that the E. coli hsp70 homolog, the dnaK gene product, protects the host RNA polymerase enzyme from heat inactivation in an ATP-independent reaction. In addition, we show that heat-inactivated and aggregated RNA polymerase is both disaggregated and reactivated following simultaneous incubation with DnaK protein and hydrolyzable ATP. The DnaK756 mutant protein has lost the ability to disaggregate the inactivated RNA polymerase enzyme. Our results demonstrate that the DnaK protein contributes to E. coli's growth not only by protecting some enzymes from denaturation but also by reactivating some once they are misfolded or aggregated. PMID- 2203540 TI - Role of eukaryotic-type functional domains found in the prokaryotic enhancer receptor factor sigma 54. AB - E. coli sigma 54 protein confers on promoters containing its recognition sequence the ability to be activated from distant DNA sites. Its functional domains include two leucine zipper motifs, an acidic region, and a glutamine-rich domain. Several domains were disrupted and the assembly of mutant transcription complexes was probed in vivo by footprinting. Promoter recognition was seen to depend on a C-terminal region containing a prokaryotic helix-turn-helix motif. Within the resulting stable closed complex, two leucine zipper motifs assist in positioning the sigma 54 polymerase near the DNA region that must be melted upon activation. Finally, DNA opening depends on the sigma 54 acid domain. The uncoupling of promoter recognition from DNA melting, mediated by the unusual domain structure of this prokaryotic protein, may be responsible for sigma 54,s ability to mediate activation from distant sites. PMID- 2203541 TI - The role of dam methyltransferase in the control of DNA replication in E. coli. AB - The timing and control of initiation of DNA replication in E. coli was studied under conditions where the cellular level of dam methyltransferase was controlled by a temperature-inducible promoter. Flow cytometry was used to demonstrate that the synchrony of initiation at the several origins within each cell was critically dependent on the level of dam methyltransferase. Initiations were shown to be synchronous only in a narrow temperature range. The data are explained by a model where a newly replicated and therefore hemimethylated oriC is inert for reinitiation. Such a model may be applicable to eukaryotic cells, where classes of origins are initiated in synchrony and only once per cell cycle. PMID- 2203542 TI - Intermediate filament assembly and stability in vitro: effect and implications of the removal of head and tail domains of vimentin by the human immunodeficiency virus type 1 protease. AB - The intermediate filament subunit protein vimentin is efficiently cleaved in vitro by purified human immunodeficiency virus type 1 protease. Immunological data confirm that identical sites are cleaved when vimentin is polymerized into filaments or occurs as protofilaments. The primary cleavage gives rise to a molecule lacking most of the tail domain and which not only remains in preformed filaments, but is also capable of polymerizing into essentially normal 10 nm filaments. However, these filaments show a propensity to form large lateral aggregates. The three secondary cleavage products of vimentin additionally lack portions of the head domain, are almost quantitatively (greater than 95%) released from preformed filaments and are not capable of forming filaments de novo. These results extend the limits of the head and tail domains of vimentin that play a role in filament formation and stability. PMID- 2203543 TI - Some characteristics of rabbit anti sea star T-like cells serum. AB - Preliminary experiments show that rabbit anti sea star T-like serum recognizes T like cells from two different geographic regions but not mouse T lymphocytes and man T lymphocytes. On the other hand, cytotoxicity reactions do not occur with this serum. PMID- 2203544 TI - Recruitment: the ins and outs of spindle pole formation. AB - Microtubule-organizing centers are a diverse but interrelated set of cellular organelles that appear when needed at specific times in the cell cycle. Diversity is introduced into MTOCs, and thus into microtubule structures, by post translational modification, by morphological changes, by de novo synthesis, and by recruitment of cytoplasmic proteins. Understanding the mechanisms that lead to such diversity should contribute to a better understanding of the myriad of cellular events which depend on microtubules. PMID- 2203545 TI - [Metabolites with immunoregulatory effects isolated from higher plants]. PMID- 2203546 TI - [Immunologic parameters in insulin-dependent diabetes mellitus in children]. AB - Evaluation of some immunological indicators in a group of 31 patients. In 80.6% patients IgG and IgM values were elevated, in 77% the total lymphocytes were reduced. Significantly reduced C3 levels were recorded in 46.6% and reduced C4 levels in 83.3%, in particular during the period of decompensation. Serum antibodies against islet cells of the pancreas were found in particular during the first two years of the disease. PMID- 2203548 TI - [Diseases caused by verotoxigenic Escherichia coli]. PMID- 2203547 TI - [Verotoxigenic (enterohemorrhagic) Escherichia coli]. PMID- 2203549 TI - [From the history of allergology]. PMID- 2203550 TI - Development of vaccines against cholera and diarrhoea due to enterotoxigenic Escherichia coli: memorandum from a WHO meeting. AB - This Memorandum summarizes current knowledge on the epidemiology of cholera and diarrhoea due to enterotoxigenic Escherichia coli (ETEC) and outlines the results of recent research to develop an effective oral vaccine against cholera. The meeting reviewed current research on the protective antigens of ETEC and made a number of recommendations with the aim of stimulating further efforts towards the development of vaccines against disease caused by ETEC. PMID- 2203551 TI - Primary prevention of colorectal cancer. The WHO Collaborating Centre for the Prevention of Colorectal Cancer. AB - Colorectal cancer is the third most common malignant neoplasm worldwide. Epidemiological and laboratory animal studies have established a link between various nutritional factors and the etiology of this cancer. Recent studies in genetic epidemiology and molecular biology have shown that inherited genetic factors also play an important role in colorectal carcinogenesis. Thus, genetic nutritional interactions may form the basis for the development of this cancer. Nutritional factors that appear to promote or attenuate the carcinogenic process in the colon include fat, excess calories, fibre, calcium, selenium, and various vitamins. Strategies for primary prevention of colorectal cancer should therefore be targeted to all populations who are at risk because of dietary and hereditary predisposition. Based on current knowledge, recommended nutrition guidelines for reducing the risk of colon cancer include decreased fat consumption, adequate amounts of fruits, vegetables, and calcium, and avoidance of overweight. Research to further elucidate the role of diet in colorectal carcinogenesis should include randomized studies in humans, testing of various nutritional regimens, and the use of colonic adenomas and markers of cell proliferation and differentiation as end-points. PMID- 2203552 TI - Clinical applications of transesophageal echocardiography. PMID- 2203553 TI - Mechanism of myocardial "stunning". AB - Among the numerous mechanisms proposed for myocardial stunning, three appear to be more plausible: 1) generation of oxygen radicals, 2) calcium overload, and 3) excitation-contraction uncoupling. First, the evidence for a pathogenetic role of oxygen-derived free radicals in myocardial stunning is overwhelming. In the setting of a single 15-minute coronary occlusion, mitigation of stunning by antioxidants has been reproducibly observed by several independent laboratories. Similar protection has been recently demonstrated in the conscious animal, that is, in the most physiological experimental preparation available. Furthermore, generation of free radicals in the stunned myocardium has been directly demonstrated by spin trapping techniques, and attenuation of free radical generation has been repeatedly shown to result in attenuation of contractile dysfunction. Numerous observations suggest that oxyradicals also contribute to stunning in other settings: after global ischemia in vitro, after global ischemia during cardioplegic arrest in vivo, and after multiple brief episodes of regional ischemia in vivo. Compelling evidence indicates that the critical free radical damage occurs in the initial moments of reflow, so that myocardial stunning can be viewed as a sublethal form of oxyradical-mediated "reperfusion injury." Second, there is also considerable evidence that a transient calcium overload during early reperfusion contributes to postischemic dysfunction in vitro; however, the importance of this mechanism in vivo remains to be defined. Third, inadequate release of calcium by the sarcoplasmic reticulum, with consequent excitation-contraction uncoupling, may occur after multiple brief episodes of regional ischemia, but its role in other forms of postischemic dysfunction has not been explored. It is probable that multiple mechanisms contribute to the pathogenesis of myocardial stunning. The three hypotheses outlined above are not mutually exclusive and in fact may represent different steps of the same pathophysiological cascade. Thus, generation of oxyradicals may cause sarcoplasmic reticulum dysfunction, and both of these processes may lead to calcium overload, which in turn could exacerbate the damage initiated by oxygen species. The concepts discussed in this review should provide not only a conceptual framework for further investigation of the pathophysiology of reversible ischemia-reperfusion injury but also a rationale for developing clinically applicable interventions designed to prevent postischemic ventricular dysfunction. PMID- 2203554 TI - Early diagnosis of acute myocardial infarction based on assay for subforms of creatine kinase-MB. AB - Thrombolytic therapy for patients with acute myocardial infarction (AMI) has produced the need for an accurate early diagnostic marker. We previously developed and assessed an assay for the creatine kinase (CK)-MB subforms; assay time is 25 minutes. Plasma MB2 (tissue subform) activity, MB1 (plasma-modified subform) activity, and MB2/MB1 ratio in 56 healthy individuals were 0.61 +/- 0.33 units/l, 0.63 +/- 0.33 units/l, and 0.94 +/- 0.39, respectively. Only one individual had both an MB2 activity greater than 1.0 units/l and an MB2/MB1 ratio of more than 1.5. Similar results were obtained in 50 hospitalized patients without cardiac disease; two of these patients had both an MB2 activity and an MB2/MB1 ratio greater than the cutoff values. Among 49 patients with AMI, MB2 activity and the MB2/MB1 ratio began to increase 2 hours after AMI; the ratio reached a plateau of 3.1 by 4-6 hours. The first available plasma sample was abnormal by the subform assay in 67% of patients and by a conventional MB assay in 27% of patients. Assay sensitivities in samples collected at 2-4, 4-6, and 6-8 hours after AMI were 59%, 92%, and 100% for the subform assay and 23%, 50%, and 71% for the conventional assay (p less than 0.03 versus subform assay at each time interval). False-negative results were obtained by the subform and conventional assays in 15 and 45 samples at a mean of 2.3 and 5.8 hours, respectively. Subform assay provides rapid and reliable diagnosis of AMI within 4 6 hours after the onset of symptoms, which is 6 hours before conventional CK-MB assays are accurate. PMID- 2203555 TI - Prevention of early aortocoronary bypass occlusion by low-dose aspirin and dipyridamole. Grupo Espanol para el Seguimiento del Injerto Coronario (GESIC) AB - To analyze the efficacy of low-dose aspirin in preventing early aortocoronary vein graft occlusion, 1,112 consecutive patients were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial comparing 50 mg t.i.d. aspirin, 50 mg aspirin plus 75 mg t.i.d. dipyridamole, and placebo. All patients received 100 mg q.i.d. dipyridamole for 48 hours before surgery, and assigned treatment was started 7 hours after surgery. Vein graft angiography was performed in 927 patients (83%) within 28 days of surgery (mean, 10 days). Aspirin plus dipyridamole significantly (p = 0.017) reduced the occlusion rate of distal anastomoses from 18% (placebo) to 12.9%. Occlusion rate in the aspirin group was 14%, which approached statistical significance (p = 0.058). Furthermore, only aspirin plus dipyridamole reduced (p = 0.01) the number of patients with occluded grafts (placebo, 33%; aspirin, 27.1%; aspirin plus dipyridamole, 24.3%). Mediastinal drainage was slightly higher (p = 0.04) in the aspirin plus dipyridamole group (713 +/- 456 ml) than in the other two groups (placebo, 670 +/ 437 ml; aspirin, 629 +/- 337 ml), but hospital mortality (average, 4.6%) and early reoperation (average, 3.9%) rates were similar among the three groups. Thus, low-dose aspirin plus dipyridamole safely improves early saphenous vein aortocoronary graft patency; this effect is an added benefit to a preoperative regimen of dipyridamole. PMID- 2203556 TI - Circadian variation of acute myocardial infarction and the effect of low-dose aspirin in a randomized trial of physicians. AB - Increased platelet aggregation in the morning and upon assuming an upright posture may account at least in part for the observed circadian variation in onset of acute myocardial infarction. The Physicians' Health Study, a randomized, double-blind, placebo-controlled trial of alternate-day aspirin intake (325 mg) among 22,071 US male physicians, afforded the opportunity to assess this circadian pattern and examine whether it is altered by aspirin therapy. During a 5-year period of follow-up, 342 cases of nonfatal myocardial infarction were confirmed, of which the time of onset was available in 211 (62%). The placebo group showed a bimodal circadian variation in onset of myocardial infarction with a primary peak between 4:00 AM and 10:00 AM (p less than 0.001). In the aspirin group, however, this circadian variation was minimal (p = 0.16), due primarily to a marked reduction in the morning peak of infarction. Specifically, aspirin was associated with a 59.3% reduction in the incidence of infarction during the morning waking hours, compared with a 34.1% reduction for the remaining hours of the day. The greater reduction was observed during the 3-hour interval immediately after awakening, a period with a risk of infarction twice that of any other comparable time interval (p less than 0.001). Aspirin intake was associated with a mean reduction in the incidence of infarction of 44.8% over the entire 24 hour cycle. These data support the hypothesis that increased platelet aggregability in the morning and upon arising contributes to the occurrence of myocardial infarction and that aspirin reduces the risk of infarction by inhibiting platelet aggregation during these critical periods. PMID- 2203557 TI - Revascularization for acute myocardial infarction. Strategies in need of revision. AB - Prompt reperfusion of the ischemic myocardium by the successful use of thrombolytic agents in the setting of acute myocardial infarction has substantially reduced mortality among patients judged eligible for their use. This approach has revolutionized the management of acute infarction patients worldwide. Such therapy, however, is associated with increased rates of reinfarction and postinfarction angina that have been attributed to the underlying residual atherosclerotic lesion. The expectation that coronary angioplasty would provide the logical solution to this clinical problem has been considerably lowered by the results of a number of prospective randomized clinical trials. These findings, coupled with the realization that as many as 50% of patients suffering acute infarctions will not safely qualify for the use of thrombolytic agents, present compelling reasons to more accurately investigate the role of primary angioplasty and bypass surgery as a means of effecting reperfusion therapy in the setting of acute infarction. PMID- 2203558 TI - Catecholamines in myocardial ischemia. Systemic and cardiac release. AB - During myocardial ischemia, malignant arrhythmias and acceleration of cell damage may be induced by sympathetic overstimulation of the heart. This stimulation is due to excessive concentrations of catecholamines within the underperfused myocardium, in combination with enhanced myocyte sensitivity to adrenergic stimuli. Various mechanisms may account for local accumulation of catecholamines in the extracellular space of the ischemic but still viable myocardium. In early myocardial infarction, plasma noradrenaline and adrenaline concentrations are enhanced, reflecting increased activity of the whole sympathetic nervous system, rather than local activity in the heart. In uncomplicated infarction, these concentrations are only five times the normal levels at rest, and there are no convincing data that these mildly increased levels of plasma catecholamines directly induce a major deterioration of myocardial function during the ischemic process. Of more importance is the reflex increase in cardiac sympathetic nerve activity that is induced by pain, anxiety, and a fall in cardiac output or arterial blood pressure and that is accompanied by local exocytotic release of noradrenaline from sympathetic nerve endings of the heart. Excessive accumulation of the neurotransmitter, however, is prevented by at least three mechanisms: 1) Released noradrenaline is rapidly removed so long as neuronal catecholamine reuptake is functional. 2) Adenosine accumulating in the ischemic myocardium effectively suppresses exocytotic noradrenaline release by stimulating presynaptic A1-adenosine receptors. 3) Exocytotic catecholamine release ceases when the sympathetic neurons become depleted of adenosine triphosphate since this release mechanism requires high-energy phosphates. However, with progression of ischemia (i.e., greater than 10 minutes), the myocardium is no longer protected against excess adrenergic stimulation since local metabolic release mechanisms become increasingly important. This release, which is independent of both central sympathetic activation and extracellular calcium, occurs in two steps. First, catecholamines escape from their storage vesicles and accumulate in the cytoplasm of the neuron. In the second, rate-limiting step, noradrenaline is transported across the axolemma from the cytoplasm to the interstitial space via the neuronal uptake carrier in reverse of its normal transport direction. As a consequence of this nonexocytotic local metabolic release, extracellular noradrenaline reaches 100-1,000 times its normal plasma concentrations within 30 minutes of ischemia. Concentrations of this magnitude are capable of producing myocardial necrosis, even in the nonischemic heart, and may play an important role in the pathogenesis of ventricular fibrillation in early ischemia. PMID- 2203559 TI - Is silent ischemia a treatable risk factor in patients with angina pectoris? AB - Silent myocardial ischemia is increasingly recognized as a common phenomenon in a variety of populations with coronary artery disease. In patients with angina pectoris, this condition has been recognized during either exercise stress testing or ambulatory monitoring when ischemic-type ST-segment shifts occur without symptoms. Although more information is clearly needed, available data suggest an important independent relation between ambulant ischemia, most of which is silent, and adverse outcome. Other studies show that currently available antianginal agents can prevent or modify symptomatic as well as silent ischemic episodes. Several reports indicate that when these agents are prescribed to control symptomatic ischemic episodes, silent ischemia may continue to occur. Yet, when antianginal drugs are used either alone or in combination in those with recurrent silent ischemia, both the frequency and duration of the silent ischemic episodes are greatly reduced. To date, however, no data are yet available on the impact on outcome of a strategy directed at detecting and treating silent ischemia. Until this information is available, more attention should be focused on identifying and adequately controlling ischemia rather than on simply managing chest pain. PMID- 2203560 TI - Silent ischemia after myocardial infarction. Prognosis, mechanism, and intervention. AB - Asymptomatic ischemia after myocardial infarction is a common clinical problem. As much as 50% of the postinfarction patient population who have ischemia on exercise testing may have no symptoms at all. In these patients, ischemia detected by either exercise testing or ambulatory electrocardiographic monitoring, with or without symptoms, confers a worse prognosis. The mechanism of silent ischemia in this group of patients may be due to the deprivation of afferent innervations created by critically placed infarctions. The management of these postinfarction patients must be centered on the treatment of ischemia, regardless of symptoms. PMID- 2203561 TI - Should silent ischemia be treated in asymptomatic individuals? AB - In the United States, there may be as many as two million totally asymptomatic men with silent myocardial ischemia due to coronary artery disease. Because detection of such patients is often fortuitous, a rigorous screening protocol has been suggested for high-risk subgroups (i.e., persons with multiple coronary risk factors and/or family histories of premature coronary artery disease). At present, the initial procedure of choice for a screening protocol is the exercise test, followed by radionuclide procedures to differentiate true-positive from false-positive responses if coronary angiography is being considered. Holter monitoring is useful in documenting out-of-hospital ischemic events in asymptomatic patients with documented coronary artery disease. Prognostic studies in patients with and without coronary angiographic data indicate that asymptomatic patients with an ischemic ST-segment depression on exercise tests comprise a high-risk subgroup that has a well-defined morbidity and mortality due to future cardiac events. The angiographic surveys show that the greatest risk is in those individuals with more extensive disease. Treatment in asymptomatic persons requires the use of objective measurements as end points. Several reports have demonstrated the efficacy of beta-blockers, calcium channel blockers, and coronary angioplasty in this population, at least so far as reducing total ischemic activity is concerned. How nonsurgical therapy will affect ultimate prognosis is still unclear. However, surgical therapy in asymptomatic patients with left main coronary artery disease and triple-vessel disease has been reported to improve long-term survival. PMID- 2203562 TI - Therapeutic rationale for the management of silent ischemia. AB - Prognostic data on the importance of silent ischemia is lacking. Preliminary reports suggest that ambulatory electrocardiographic monitoring provides additional information not contained in the exercise test, but it is still unclear whether silent ischemia is a marker of subsequent events or is responsible for their development. Recent investigations also suggest that intermittent episodes of ischemia may cause myocardial necrosis. Drugs that are effective in the treatment of angina are also effective in the treatment of silent ischemia, but their value in terms of long-term morbidity and mortality is unclear. Recently, the circadian distribution of silent ischemia has been reported in 150 patients off therapy, in 33 receiving nifedipine, and in 41 receiving atenolol. Most ischemic episodes off therapy occurred between 7:30 AM and 7:30 PM with a peak in the morning and a lesser peak in the evening. Nifedipine did not alter the circadian pattern of ischemic episodes; atenolol abolished the morning peak, the peak incidence of ischemia then occurring in the evening. This circadian distribution of ischemic episodes and the observed changes with treatment resemble the reported circadian variations of acute myocardial infarction and sudden death. Large multicenter studies are now being performed to determine the effects of treatment on silent ischemia and how this treatment may influence outcome. Until such studies have been completed, it is not possible to clearly define the indication for drug therapy in the management of silent ischemia. PMID- 2203563 TI - A macro and micro view of coronary vascular insult in ischemic heart disease. AB - Atherosclerotic plaques are either concentric, producing a fixed degree of obstruction, or eccentric, with retention of an arc of normal vessel wall that allows changes in medial muscle tone to vary the degree of stenosis. Plaques may also either be solid and fibrous or may contain, in addition to fibrous thickening, a pool of extracellular cholesterol. Most subjects with ischemic heart disease have mixtures of all plaque types. The endothelium over established human plaques often shows focal denudation injury, with adhesion of a platelet monolayer not detectable by angiography. Larger thrombi are due either to superficial intimal injury, which is the progression of the endothelial denudation seen over otherwise static and intact plaques, or to deep intimal injury caused by plaque fissuring (rupture). Both forms of intimal injury expose collagen and von Willebrand factor to platelets. In deep injury, tears extend from the lumen into the depths of the intima and often enter a lipid pool; in consequence, thrombus initially forms within the plaque, thereby altering its configuration and expanding its volume. Many fissures will reseal at this stage, but the plaque is larger, and the process is an important cause of episodic sudden plaque growth. A proportion of plaque fissures are associated with the additional formation of a luminal thrombus, which may be either mural or occlusive. In life, transitions between mural and occlusive thrombi and vice versa occur rapidly and frequently. Mural thrombus is associated with distal embolization of platelet masses and, in some cases, is associated with cholesterol from the plaque.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203565 TI - Unstable angina and coronary angioplasty. AB - Of 2,122 consecutive patients undergoing elective coronary angioplasty from 1982 to 1985, 62% had stable angina pectoris (SAP), and 38% had unstable angina pectoris (UAP). There were differences between the two groups in clinical and morphological factors and in initial and late results of angioplasty. UAP patients were more likely than SAP patients to be smokers and to have had prior myocardial infarctions. Lesions in UAP patients were more severe, longer, more eccentric, more irregular, and more likely to have intracoronary thrombi than were lesions in SAP patients. Coronary angioplasty success was achieved in 84% of UAP and in 88% of SAP patients (p less than 0.05), and complications occurred in 6.7% of UAP and in 4.7% of SAP patients (p less than 0.05). Hospital death rates were low and similar, 0.2% for both groups. Follow-up (mean, 37 months) showed recurrent Canadian Cardiovascular Society (CCVS) class III/IV angina in 30.1% of UAP and in 25.2% of SAP patients (p less than 0.05). There was a return to work in 86% of UAP and in 91% of SAP patients (p less than 0.05). When UAP patients' durations of symptoms were further fractionated, it was found that the earlier angioplasty was performed after onset of angina, the lower was the success rate and the higher the complication rate and incidence of late follow-up untoward events. When coronary angioplasty was performed within 1 week of onset of angina ("early"), success was 79.1%; when angioplasty was performed 2 weeks or more after onset of angina ("later"), success was 86.3%. Major cardiac events occurred in 11.5% in the early group and in 4.8% in the later group (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203564 TI - Atherosclerotic plaque rupture and thrombosis. Evolving concepts. AB - Rupture of an atherosclerotic plaque associated with partial or complete thrombotic vessel occlusion is fundamental to the development of ischemic coronary syndromes. Plaques that produce only mild-to-moderate angiographic luminal stenosis are frequently those that undergo abrupt disruption, leading to unstable angina or acute myocardial infarction. Plaques with increased lipid content appear more prone to rupture, particularly when the lipid pool is localized eccentrically within the intima. Macrophages appear to play an important role in atherogenesis, perhaps by participating in the uptake and metabolism of lipoproteins, secretion of growth factors, and production of enzymes and toxic metabolites that may facilitate plaque rupture. In addition, the particular composition or configuration of a plaque and the hemodynamic forces to which it is exposed may determine its susceptibility to disruption. Exposure of collagen, lipids, and smooth muscle cells after plaque rupture leads to the activation of platelets and the coagulation cascade system. The resulting thrombus may lead to marked reduction in myocardial perfusion and the development of an unstable coronary syndrome, or it may become organized and incorporated into the diseased vessel, thus contributing to the progression of atherosclerosis. In unstable angina, plaque disruption leads to thrombosis, which is usually labile and results in only a transient reduction in myocardial perfusion. Release of vasoactive substances, arterial spasm, or increases in myocardial oxygen demand may contribute to ischemia. In acute myocardial infarction, plaque disruption results in a more persistent thrombotic vessel occlusion; the extent of necrosis depends on the size of the artery, the duration of occlusion, the presence of collateral flow, and the integrity of the fibrinolytic system. Thrombi that undergo lysis expose a highly thrombogenic surface to the circulating blood, which has the capacity of activating platelets and the coagulation cascade system and may lead to thrombotic reocclusion. Measurements aimed at reversing the process of atherosclerosis via cholesterol reduction and enhanced high density lipoprotein activity are encouraging. Active research is being focused on the development of new antithrombotic tools, such as inhibitors of thrombin, thromboxane, and serotonin receptor antagonists, and monoclonal antibodies aimed at blocking platelet membrane receptors or adhesive proteins. These compounds may prove useful when immediate and potent inhibition of the hemostatic system is desired. Intensive research is still needed in the areas of pathogenesis and therapeutic intervention in atherosclerosis. PMID- 2203566 TI - The prevalence of otitis media with effusion: a critical review of the literature. PMID- 2203567 TI - Osteolysis in alloarthroplasty of the hip. The role of bone cement fragmentation. AB - Movement at the interface between bone and cement and fractures of the cement can cause fragmentation of the polymethylmethacrylate (PMMA) bone cement implant. In order to obtain further information about the effect of PMMA fragments on the surrounding tissue and the role of such particles in the development of bone resorption, the authors investigated 17 patients with cemented total hip endoprostheses showing osteolysis and implant loosening in the femoral shaft with (Group B) and without (Group A) involvement of the acetabulum. The roentgenographic follow-up examinations revealed an initially slow and later more rapid extension of the endosteal bone erosions, with a predilection for the tip of the stem, the lesser trochanter, and laterally for the middle of the stem. At revision surgery, tissue samples were taken from the joint capsule and the bone cement interface, in particular from the osteolysis in the femoral shaft and the acetabulum. The tissue samples were processed for histology, microscopically examined, and semiquantitatively evaluated. The retrieved devices were also carefully inspected. Large foreign-body granulomas were found at the bone-cement interface and in the joint capsule. Histiocytes and foreign-body giant cells stored particles of PMMA and polyethylene, of which fragmented bone cement predominated. Granulomatous tissue invaded bone canals and marrow spaces and induced resorption of the surrounding bone. In four cases in Group A, tissue from the osteolysis contained only fragmented bone cement, demonstrating that PMMA particles alone may be responsible for triggering focal bone resorption. Osteolysis seems to begin at the site where disintegration of bone cement begins. In cases in which polyethylene particles were found in the tissue in addition to fragmented bone cement, wear from the ultrahigh molecular weight polyethylene socket has been increased by entrapment of PMMA particles between the joint surfaces. Thus, fragmentation of bone cement and abrasion of polyethylene enhance each other. Bone cement particles promote polyethylene wear, which in turn promotes granuloma formation, bone resorption, and subsequent bone cement disintegration. PMID- 2203568 TI - Ultrasound examination for the early determination of dysplasia and congenital dislocation of neonatal hips. AB - Hip sonography enables an accurate and clinically relevant evaluation of hip maturation during the first days of human life. Experience has shown that an integration of hip sonography into neonatal screening programs is useful and necessary because clinical and even roentgenographic examination does not always establish a confirmed diagnosis of dysplasia. PMID- 2203570 TI - Failure of a knee prosthesis accelerated by shedding of beads from the porous metal surface. AB - A 61-year-old man who received a porous-metal-coated knee implant returned eight months later with chronic synovitis, instability, and loosening of his artificial joint. Subsequently, metal beads were detected in the joint space and soft tissues and were also embedded in the articulating surface of the tibial component. There was scoring of the tibial surface, and polyethylene wear particles were noted in the synovial and fibroconnective-tissue membranes, which had formed beneath the tibial component. Many particles were seen inside giant cells and macrophages. Failure in this case was probably accelerated by the granulomatous response in the soft tissue to wear particles. There was osteolysis rather than new bone growth at the interface with the tibial component. Analysis indicated that poor bead-bonding strength may have initiated the problem. Careful appraisal of the outcome from use of beaded porous-metal-coated devices and assurance of their adequate bonding strength are essential for further progress. PMID- 2203569 TI - Knock-knee deformity in children. Congenital and acquired. AB - The causes of knee valgus in children are multiple and complex. Physiologic knock knee, trauma, poliomyelitis, dysplasias, and infection all can be causative. One of the most interesting examples is the valgus that sometimes follows an undisplaced proximal tibial metaphyseal fracture. Treatment for all these entities can vary from doing nothing to corrective osteotomies, stapling of the medial epiphyseal plate, and bracing of the leg. PMID- 2203571 TI - Mycobacterial prepatellar bursitis. AB - Prepatellar bursitis secondary to infection with an atypical mycobacterium developed in an 88-year-old man. A review of all previously reported cases in the English literature indicates tuberculosis is important in the differential diagnosis of prepatellar bursitis. PMID- 2203572 TI - Skeletal tissue response to cytokines. AB - Communication among individual cell types that populate connective tissues such as cartilage or bone is of critical importance in determining the phenotypic properties of these tissues under both physiologic and pathologic conditions. Cytokines, which may be defined as soluble products released from one cell that can modulate the activity of other cells, play a critical role in this process of cell communication. The introduction of molecular biologic techniques has permitted identification of specific cytokines previously characterized on the basis of biologic activities. Cloning and sequencing of these products have provided formal evidence for their existence and allowed identification of the full spectrum of their biologic activities. These results have established that individual cytokines may have multiple biologic activities and that multiple cytokines share common functional properties. Based on these results, the term "cytokine" has been used more generally to include products originally described as growth or differentiation factors, e.g., interleukins, monokines, or lymphokines. Cytokines have an important role in the initiation and control of skeletal tissue growth and development and in regulating bone remodeling in the adult organism. As in other connective tissues, these effects are mediated via paracrine, autocrine, and endocrine mechanisms. In skeletal tissues, cytokines may modulate the activity of resident cells by an additional mechanism. Factors produced locally within bone or arriving via the circulation are incorporated into the mineralized bone matrix, and their release during skeletal remodeling could provide the basis for coupling the activity of bone resorbing and forming cells. The principal cytokines that have been shown to affect skeletal tissues include factors previously described as monokines or lymphokines such as interleukin-1 (IL-1), tumor necrosis factors (TNF-alpha and TNF-beta), and interferon-gamma (IFN-gamma); the colony-stimulating factors; and the so-called growth and differentiation factors including transforming growth factors-alpha and -beta (TGF-alpha and TGF-beta), insulinlike growth factor-I (IGF-I), platelet derived growth factor (PDGF), and fibroblast growth factor (FGF). Although the effects of the individual cytokines are diverse, it is possible to classify individual factors based on their effects on specific aspects of bone formation or resorption. Significant progress has been made recently toward elucidating the mechanisms of action of the cytokines. Binding studies using radiolabeled ligands have characterized the specific cell surface receptors and defined their distribution and properties among skeletal tissue cells. Various so-called signal transduction pathways have been implicated in mediating these effects... PMID- 2203573 TI - Bone physiology. 1926. PMID- 2203574 TI - Surgical treatment of congenital dislocation of the hip. AB - The results of two collective studies on congenital dislocation of the hip (CDH) from a number of hospitals are reported here, including general trends in the Federal Republic of Germany and the author's personal methods and preferences. In the first collective study group, the rate of ischemic necrosis in open reductions was 8.2% for anterolateral approaches, 9.6% for inguinal, 16.7% for Ludloff's operation, and only 5.5% when shortening osteotomy was combined with open reduction. A simultaneous Salter osteotomy or acetabuloplasty increased the rate to 10.3% and a concomitant varus osteotomy to 22.2%. The author prefers an inguinal approach to the hip joint, first laterally and then medially of the iliopsoas muscle and femoral nerve, for optimal visualization of the acetabulum. Stability of the joint is increased by a girdle-like flap from the dorsolateral capsule, which is drawn anteriorly and prevents dorsal redislocation. Acetabuloplasty should also be used, even during the first year of life, in joints in which stability may only be guaranteed by extreme abduction and internal rotation. Salter's and Pemberton's osteotomies are used in Germany with good results. However, the author prefers a lateral Albee-Lance acetabuloplasty modified to a complete osteotomy for lateral levering of the acetabular roof. Long-term results show measurements between 82% and 93% of normal and slightly pathologic values. Simultaneous or single varus osteotomies lead to subcapital coxa valga and should no longer be used routinely. In adolescents and adults up to 45 years of age, as long as osteoarthritis is not too advanced and the femoral head is not too deformed, triple pelvic osteotomy with the author's type of modification has a number of advantages. PMID- 2203575 TI - Recent advances in the surgical treatment of rheumatoid arthritis. AB - Arthritis surgery in the Federal Republic of Germany is an established subspecialty of orthopedic surgery. The scientific organization Arbeitgemeinschaft fur Rheumaorthopadie (Association for Rheumatic Orthopedics) is an official section of the Deutsche Gesellschaft fur Orthopedics and Traumatology) and has very close connections with the European Rheumatoid Arthritis Surgical Society. There are many common activities within this group, especially regarding uniform documentation, which began with the elbow. Furthermore, there are standardized procedures in operative synovectomy, including new trends, e.g., arthroscopic synovectomy. Another special interest is focused on alternatives to endoprosthetic replacement, in particular on resection interposition arthroplasty. With regard to endoprosthetic replacement, the question of cementing or not is controversial; however, there are strong arguments for cementless fixation, especially for hip endoprostheses. Arthritis surgery in Germany reflects modern trends all over the world where rheumatology is a subspecialty bridging the gap between internal medicine and orthopedics. PMID- 2203576 TI - The artificial substitution of missing hands with myoelectrical prostheses. AB - The fitting of upper-extremity amputees requires special efforts, and its significance has been increased by the development of myoelectrically controlled prosthetic arm. Although an artificial hand only represents a relatively modest substitute for the missing hand of human beings, the efforts of designers and the achievements of manufacturers should not go unnoticed. Because of the development of myoelectrically controlled prosthetic arm, the amputee's standard of function can be improved and a cosmetic and functional solution provided. For control of the electromechanical hand, muscular potentials are received from the residual limb surface, amplified in the electrodes, and transmitted as control signals to the distal area. An important factor in providing a successful fitting is a reliable man-machine connection. This article summarizes the historic development and state of the art of the myoelectrically controlled arm prosthesis. The components and technical evaluations of the Myobock system as well as the procedures for fitting and fabricating a below-elbow prosthesis have been improved recently. A critical analysis of adaptive hands suggests that the prospects for the future are good. PMID- 2203577 TI - Osteolysis in alloarthroplasty of the hip. The role of ultra-high molecular weight polyethylene wear particles. AB - Massive localized osteolysis around artificial joints has been seen more frequently in the past few years. It is still not generally accepted that ultra high molecular weight polyethylene (UHMWPE) wear particles can induce massive bone resorption, even distant from the joint. This article describes a series of eight soft-top prostheses with large UHMWPE ball heads that contributed to the erosion of surrounding bone. Roentgenographically, all of the cases showed a marked loss of proximal cortical bone, more or less combined with osteolysis, which was distal to the femoral shaft and deep into the acetabulum. In two cases, remodeling and resorption transformed the bone into a tumorlike appearance. Tissue samples from areas of osteolysis as well as from the joint capsule were taken at revision surgery, processed for histology, examined microscopically, and evaluated semiquantitatively. The retrieved devices were also carefully inspected. Large amounts of UHMWPE wear debris were found not only in the joint capsule but also in layers of granulomatous tissue from the acetabulum and femur, whereas metal particles and fragmented polymethylmethacrylate were either completely absent or occurred only in very small amounts. The results of this study demonstrate that UHMWPE wear products alone can cause massive osteolysis by triggering foreign-body granuloma formation at the bone-cement interface; the bone cement may remain fixed in areas beyond the osteolytic transformation. PMID- 2203578 TI - Problems in pharmacokinetic investigations in patients with HIV infection. PMID- 2203580 TI - Clinical pharmacokinetics of ketoprofen and its enantiomers. AB - Ketoprofen, a potent nonsteroidal anti-inflammatory drug (NSAID) of the 2 arylpropionic acid class, has been used clinically for over 15 years in Europe, and has recently been introduced in the United States. Although it possesses a chiral centre, with only the S-enantiomer possessing beneficial pharmacological activity, all ketoprofen preparations to date are marketed as the racemate. Ketoprofen exhibits little stereoselectivity in its pharmacokinetics. The enantiomers have similar plasma time-courses and do not seem to interact with one another. Hence, the data generated using nonstereospecific assays may be used to explain the pharmacokinetics of individual enantiomers. The absorption of ketoprofen is rapid and almost complete when given orally. Sustained release dosage forms are available, which may be beneficial due to the short terminal phase half-life of ketoprofen (1 to 3h). They may also decrease local gastrointestinal side effects. Although with these preparations the peak plasma drug concentration is reduced and time to peak is prolonged, the bioavailability is the same as that with regular release counterparts. Ketoprofen binds extensively to plasma albumin, apparently in a stereoselective manner. Substantial concentrations of the drug are attained in synovial fluid, the proposed site of action of NSAIDs. It is eliminated following extensive biotransformation to inactive glucuroconjugated metabolite. There is about 10% R to S inversion upon oral administration. Conjugates are excreted in urine, and virtually no drug is eliminated unchanged. The excretion of conjugates is closely tied to renal function; accumulation of conjugates occurs in the elderly, but not in young subjects or patients. Significant drug interactions have been demonstrated for probenecid, aspirin and methotrexate. There appears to be circadian variation, particularly in the absorption of ketoprofen. The relationship between concentration and anti-inflammatory effect has yet to be elucidated for this drug. PMID- 2203579 TI - Clinical pharmacokinetics of the newer ACE inhibitors. A review. AB - The orally active angiotensin-converting inhibitors (ACE inhibitors) such as captopril and enalapril represent a significant therapeutic advance in the treatment of hypertension and congestive heart failure. Enalapril differs from captopril in several respects. It is a prodrug converted by hepatic esterolysis to the active (but more poorly absorbed) diacid, enalaprilat. Enalaprilat is more potent than captopril, more slowly eliminated and does not possess a sulfhydryl (SH) group. Enalapril was rapidly followed by a number of newer ACE inhibitors, the majority of which are similar to enalapril in that they are prodrugs, converted by hepatic esterolysis to a major active but poorly absorbed diacid metabolite. In one case (delapril) there are 2 active metabolites; in another (alacepril) the prodrug is converted in vivo to captopril. Lisinopril is an exception in that it is an enalaprilat-like diacid but with acceptable oral bioavailability, so that the prodrug route is not employed. The newer ACE inhibitors are at widely different stages of development, and it is not yet clear how many will reach regular clinical use. Of these newer drugs, lisinopril is the longest established and is the subject of the widest published literature. For a number there is as yet little published pharmacokinetic information. A variety of assay methods have been employed to characterise the pharmacokinetics of the ACE inhibitors, including enzymatic techniques, radioimmunoassay and chromatography. The peak plasma concentrations of the prodrugs are generally observed at around 1 hour and those of the diacid metabolites at about 2 to 4 hours. However, there is considerable variation within and between drugs, with benazepril and benazeprilat reaching peak concentrations early and enalapril and enalaprilat typical of later times to peak. Absorption of the active diacids is generally poor, and moderate (typically 30 to 70%) for the prodrugs. The bioavailability of lisinopril is about 25%. It is difficult to talk meaningfully about half-lives of the active drugs. The declines in their plasma concentrations are polyphasic and, if analytical sensitivity allows, active drug may be found at 48 hours or more following administration. This may reflect binding to ACE in plasma. Half-lives of accumulation are of the order of 12 hours; protein binding varies from little (lisinopril) to 90% (benazeprilat). Elimination is mostly renal but there may be biliary elimination for some, such as benazeprilat and fosinopril. The half-lives of the prodrugs are short. Impaired renal function decreases the elimination rate of the diacids.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2203583 TI - Computed tomography in adult obliterative bronchiolitis. PMID- 2203582 TI - How good are case notes in the audit of radiological investigations? AB - Audit based on the use of case notes completed in the ordinary course of patient care has not been widely used because of concern about the completeness and adequacy of such records. This paper describes the results of a study carried out to assess whether information contained in case notes was sufficiently reliable to enable clinical effectiveness to be measured. The study examines the extent to which a radiologist and an epidemiologist agree with two experienced clinicians in making retrospective judgements on whether out-of-hours radiological investigations are worthwhile. There was a high measure of agreement; only a relatively small amount of information in the case notes is needed to make valid judgements on clinical performance. The method described here may be applicable to other diagnostic investigations and the results of the study have wide implications for more effective and efficient management of resources within the NHS. PMID- 2203584 TI - Computed tomography of idiopathic retroperitoneal fibrosis ('periaortitis'): variants, variations, patterns and pitfalls. PMID- 2203585 TI - Radionuclides and the gut. PMID- 2203587 TI - Medicare Volume Performance Standard (MVPS). PMID- 2203581 TI - Disease-induced variations in plasma protein levels. Implications for drug dosage regimens (Part II). AB - Part I of this article, which appeared in the previous issue of the Journal, discussed the implications of variations in plasma protein levels in a number of diseases: hepatic and renal disease, acute myocardial infarction, burns, cancer, diabetes mellitus, hyperlipidaemia and inflammatory diseases. In Part II the authors continue their review with a further range of disease states, and consider their import for drug dosages. PMID- 2203586 TI - Rupture of the right hemidiaphragm following blunt trauma: the use of ultrasound in diagnosis. AB - Diaphragmatic rupture occurs in approximately 5% of patients who sustain multiple trauma and post-mortem studies suggest that right-sided rupture is more common than generally realized. Four cases of rupture of the right hemidiaphragm secondary to blunt trauma are presented. The chest radiographs were all similar, demonstrating a right sided fluid collection and right lower lobe consolidation in all patients. No patient had a pneumothorax. CT was useful only in retrospect, demonstrating a posterior eventration of the liver into the thorax in two patients. Ultrasound proved diagnostic in all cases demonstrating either the free edge of the diaphragm as a flap within the pleural fluid or the liver herniating into the thorax. The value of ultrasound as a simple, non-invasive and direct means of imaging the diaphragm is emphasized. PMID- 2203588 TI - Antibodies to DNA in patients with systemic lupus erythematosus. Their role in the diagnosis, the follow-up and the pathogenesis of the disease. AB - In this paper an overview of the present knowledge on antibodies against DNA will be presented. Diagnostic, prognostic and pathogenic aspects of anti-DNA will be highlighted. Detection of antibodies to DNA in the circulation of a patient by an assay selective for high avidity anti-DNA is highly diagnostic for SLE. Anti-DNA of low avidity occurs in rheumatic diseases other than SLE as well, making detection of such antibodies of less diagnostic value. Furthermore, data will be presented that show that the anti-DNA ELISA in its present form is not suited as a diagnostic tool. Not only disease features of SLE vary from patient to patient, anti-DNA avidity does so too. A relationship between anti-DNA avidity and clinical features can be found: high avidity anti-DNA is more abundant in patients with nephritis, low avidity anti-DNA in patients with CNS involvement. Prognostically, a steady increase of the level of high avidity anti-DNA generally heralds an upcoming exacerbation in a patient. Furthermore, 85% of the patients who do not have SLE at the time (high avidity) anti-DNA is detected in their serum, will develop the disease within the next few years. It is noteworthy, that patients with only low avidity anti-DNA in their circulation develop a more mild form of SLE; the (low) avidity of their anti-DNA seldomly increases during the course of their disease. The relevance of anti-DNA to the pathogenesis of SLE still is a matter of debate. On the one hand, the association of parameters of anti-DNA that determine the size of the complexes formed with DNA is in favour of the classical hypothesis, which states that SLE is primarily an immune complex disease. On the other hand, recent data on crossreactions of anti-DNA with phospholipids, glycosaminoglycans and other (poly-negative) structures plead for a role of such crossreactivities in the pathogenesis of SLE. PMID- 2203589 TI - The role of anti-DNA antibodies in lupus nephritis. PMID- 2203590 TI - Anti-Ro antibodies and neonatal lupus. PMID- 2203592 TI - Anti-centromere antibodies (ACA). PMID- 2203591 TI - Anti-Ro (SSA)/La (SSB) antibodies and Sjogren's syndrome. AB - Antibodies to Ro (SSA) and La (SSB) cellular ribonucleoprotein complexes are found in the circulation of patients with Sjogren's syndrome (SS), mainly in those with the primary form of the syndrome. Their presence is associated with long disease duration, earlier disease onset, parotid gland enlargement, systemic manifestations and also with hypergammaglobulinemia, rheumatoid factors and monoclonal type II cryoglobulins. While anti-Ro (SSA) antibodies are not specific for SS, anti-La (SSB) antibodies seem to be specific. Studies of HLA class II molecules in Ss patients with and without these antibodies have shown that their production is under genetic control. Finally, there is no conclusive evidence relating pathogenetically these autoantibodies to tissue destruction in SS. PMID- 2203593 TI - The biochemistry and genetics of DNA and anti-DNA antibodies. PMID- 2203594 TI - Antinuclear antibody determination methods. AB - Screening rheumatology patients for anti-nuclear and anti-cytoplasmic antibodies is easily done in a qualitative manner using the IF, CIE and ID assays. The immunoblot is of use for anti-La and anti-RNP assays but gives anomalous results for Sm binding by anti-RNP sera and is not easily quantitated. These deficiencies of the immunoblot do not apply to the ELISA. Advances in cloning of autoantigens will enable standardisation of antigen preparations used for these ELISAs. The quantitation of autoantibody appears significant since disease flares occur together with elevations in specific autoantibody. IgM anti-Sm autoantibody was detected with a different disease distribution to IgG anti-Sm but the prognostic implications for this remain to be determined. PMID- 2203595 TI - A comparison of assays used for the detection of antibodies to DNA. AB - In this paper we will briefly compare four assays in use in our institute for the measurement of antibodies to DNA: the anti-DNA ELISA, the PEG assay, the indirect immunofluorescence test on Crithidia luciliae and the Farr assay. Although with the use of sera from defined patients with systemic lupus erythematosus (SLE) quite good correlations were obtained between the various assays, these correlations were lost upon the use in routine screening of sera of undefined patients. It will be shown that the Farr assay has the highest specificity to systemic lupus erythematosus, whereas the ELISA and the PEG assay are the most sensitive methods. In its present form, however, the ELISA is not suited for the detection of IgM anti-DNA. Furthermore, this technique alone also detects DNA/ anti-DNA complexes present in sera or hybridoma culture supernatants. PMID- 2203596 TI - Antinuclear antibody profiles in relation to specific disease manifestations of systemic lupus erythematosus. AB - The aim of the study was to investigate the prevalence of antinuclear and associated antibodies (anti-dsDNA, anticardiolipin, anti-RNP, anti-Sm, anti-SSA and anti-SSB) and/or combinations thereof in systemic lupus erythematosus (SLE) patients with respect to their diagnostic and pathogenetic significance. The prevalence of anti-dsDNA antibodies was strongly influenced by the selection criteria of the patient; the lowest prevalence was found in SLE patients with central nervous system (CNS) involvement; the highest prevalence in patients with nephritis. The results were also influenced by the different assays. Combinding different assays (Farr/PEG ratio) quantitative as well as qualitative differences could be shown between patients with nephritis (Farr/PEG ratio greater than or equal to 5) and with CNS involvement (Farr/PEG ratio less than 5). No difference in anticardiolipin antibody prevalence between the different SLE patient groups could be demonstrated. Regarding antibodies against RNP, Sm, SSA and SSB, the prevalence was found to be strongly influenced by the criteria used for patient selection. Only in CNS patients and association with anti-RNP and anti-SSB antibodies alone or in combination was found. In pleuropericarditis a weak association with RNP antibodies existed. IN CONCLUSION: studying the prevalence and possible pathogenetic significance of antibodies one should always consider patient selection criteria and the effect of the different assays used when analysing the results. PMID- 2203597 TI - Gamma 2-MSH increases during graded exercise in healthy subjects: comparison with plasma catecholamines, neuropeptides, aldosterone and renin activity. AB - To evaluate the possibility that the proopiomelanocortin (POMC)-derived peptide gamma 2-melanocyte stimulating hormone (gamma 2-MSH) has a role in circulatory regulation in man we studied circulating levels of this peptide at three different stages of physical activity in 10 young healthy subjects. The results were compared to simultaneously measured plasma levels of catecholamines, neuropeptide Y, vasopressin, renin activity, aldosterone and human alpha-atrial natriuretic peptide (alpha-hANP) and of the vasodilatory peptides calcitonin gene related peptide, substance P and vasoactive intestinal peptide. The plasma levels of gamma 2-MSH-LI (like immunoreactivity) increased from 1009 +/- 101 pmol l-1 at supine rest to 1281 +/- 79 pmol l-1 when measured after 10 min walking (P less than 0.05), and remained at this increased level also after a consecutive further increase of physical activity (4 min stair rush), 1293 +/- 87 pmol l-1 (P less than 0.05 vs. at rest). The increase in circulating gamma 2-MSH-LI levels preceded the elevation of the venous plasma noradrenaline level, but did not rise further with more pronounced activation of the sympathetic nervous system at the highest grade of physical activity examined. PMID- 2203598 TI - Combining statistical, rule-based, and physiologic model-based methods to assist in the management of diabetes mellitus. AB - Self-monitoring of capillary blood glucose is used by most patients with insulin dependent diabetes mellitus as a means of assessing metabolic control. Therapeutic interventions are based on retrospective analysis of glycemic response to various factors, with insulin and diet playing the key roles. We describe a computer system being developed for intelligent automated analysis and interpretation of data relevant to glycemic control. CADMO (Computer-Assisted Diabetes Monitor) is intended to assist health care professionals with the management of patients with insulin-dependent diabetes. It takes as input glucose values and insulin doses collected via a memory meter by the patient over a period of several weeks. Rule-based logic, statistical methods, and a physiologic model of insulin pharmacokinetics and glucose dynamics are used to help detect meaningful patterns and trends in glucose and insulin data and to suggest approaches for optimizing insulin regimens. PMID- 2203599 TI - Noise and hearing loss. National Institutes of Health Consensus Development Conference. PMID- 2203600 TI - Curiosity: an aperitif. PMID- 2203601 TI - 50 years ago. From the Journal of the Connecticut State Medical Society, July 1940. Modern treatment of pneumonia. PMID- 2203602 TI - Nicardipine infusion for postoperative hypertension after surgery of the head and neck. AB - The therapy of postoperative hypertension (POH) after head and neck surgery was evaluated in a prospective, randomized, double-blind trial. Nicardipine hydrochloride, a Ca channel-blocker for iv use, was compared with placebo. Patients were initially randomized to receive nicardipine infusion or placebo. Those not responding to placebo were given nicardipine infusion on an open basis. Hypertension was significantly better controlled in patients treated with nicardipine infusion compared with placebo (83% vs. 22%, p less than .002). Subsequently, six (86%) of seven of the placebo failures were successfully treated with nicardipine. There were no significant complications in either group. We conclude that the titratable infusion of nicardipine is an effective and safe method for the control of POH after surgery of the head and neck. Further studies are now warranted comparing nicardipine with other drugs currently used to treat this condition. PMID- 2203603 TI - Does pH paper accurately reflect gastric pH? AB - The testing of gastric pH in the ICU has become the standard of care for most critically ill patients. It has been demonstrated that maintaining a gastric pH of greater than 3.5 confers protection from upper GI bleeding, while lesser pH values subject the patient to hemorrhagic risk. We compared nasogastric pH, as measured by pH electrode, to color-scaled pH paper in 16 critically ill patients hospitalized 3 to 10 days in the surgical ICU. Statistical analysis of 370 gastric specimens revealed a sensitivity of 66.7% and specificity of 94.5% when a paper pH (pH[p]) of greater than or equal to 4 was used as the therapeutic end point. The sensitivity and specificity of the same pH(p) for clear buffered solutions were 100%. We conclude that the use of pH(p) lacks the clinical accuracy for determining the effects of therapy for the prophylaxis of stress gastritis and will lead to a significant degree of undertreatment. This lack of accuracy is not due to observer error or the quality or age of the testing paper. Our results suggest that if the measurement of gastric pH by pH(p) analysis is to be used as a guide for the prevention of stress-related hemorrhage, a more accurate method of monitoring may be warranted. PMID- 2203604 TI - Flow-regulated continuous positive airway pressure to minimize imposed work of breathing. AB - We have developed a new continuous positive airway pressure (CPAP) system, which consists of an electropneumatic regulator, a microcomputer, and a pneumotachograph placed between the endotracheal tube and the breathing circuit of the CPAP apparatus. This flow-regulated CPAP (FR-CPAP) system delivers a basal flow and also regulates this flow every 20 msec to match the patient's flow demand. To evaluate the performance of this FR-CPAP system, we compared the imposed work of breathing of the FR-CPAP and continuous flow CPAP (CF-CPAP) systems. A model lung was used to simulate spontaneous breathing. The imposed work of breathing of the FR-CPAP system was less than that of the CF-CPAP system. These results indicate that the FR-CPAP system could minimize the imposed work of breathing of a patient receiving CPAP. PMID- 2203605 TI - Theoretical prediction of devitrification tendency: determination of critical warming rates without using finite expansions. AB - Previously, critical warming rates vcr above which ice did not have enough time to crystallize had been roughly evaluated for many wholly amorphous aqueous solutions. These evaluations were obtained by extrapolation of the linear variation of the devitrification temperature Td with log v, where v is the warming rate, observed experimentally between 2.5 and 80 degrees C/min. Theory also gives such a linear variation, but only using the first term of a finite expansion. The other terms can be neglected only for small variations of Td. These evaluations were sufficient for classification of the solutions, but large errors were made in vcr. A new and more accurate method of determination of the variation of Td with v is presented here. The general equation giving in our models the derivative of the quantity of ice formed versus temperature T is differentiated, instead of integrated using a finite expansion. This gives an explicit expression of v versus Td assuming that the ratio xd of the quantity of ice formed at Td to the total quantity of ice formed on warming is constant. Experimentally, xd is constant within a good approximation. Theoretical curves representing the variation of Td with v have been drawn for solutions of 35 or 45% (w/w) 1,2-propanediol in water. Td never reaches the temperature of the end of melting Tm, but as v tends toward infinity, Td tends toward an asymptotic value of 0.96Tm for 35% solute. For that solution, above about 10(3) degrees C/min, Td deviates appreciably from linearity with log v, but 1/Td remains almost linear with log v up to Td congruent to 0.95Tm. Therefore, systematic comparison of the theoretical variation of Td with v with a linear variation of 1/Td with log v has been done, varying the parameters of the equations within the entire experimental range. Similar conclusions can be given for all the solutions. Experimentally for Td = 0.95Tm, the quantity of ice crystallized is generally less than 0.1% of the solution, reaching 1% only once. Therefore, a new definition of the critical warming rate vcr has been used, corresponding to extrapolation of the linear variation of 1/T with log v up to Td = 0.95Tm. New values of vcr have been calculated for all the binary systems previously studied. The order of the solutions is almost the same, but the new values of vcr are significantly smaller than the former. PMID- 2203606 TI - Clustering of ice nucleation protein correlates with ice nucleation activity. AB - Antibodies raised against a synthetic peptide specifically detect ice nucleation proteins from Pseudomonas species in Western blots. In immunofluorescent staining of whole bacteria, the antibodies reveal the protein in clusters, as indicated by patches of intense fluorescence in Escherichia coli cells heterologously expressing Pseudomonas ice nucleation genes. The abundance, size, and brightness of the clusters vary considerably from cell to cell. Their varying sizes may explain the variability in activity of bacterial ice nuclei. Growth at lower temperatures produces more ice nuclei, and gives brighter and more frequent patches, than growth at 37 degrees C. The observed clustering may thus reflect formation of functional ice nucleation sites in vivo. The presence of ice nucleation protein in clusters is also correlated with alterations in cell morphology. PMID- 2203607 TI - Retrovirus phylogeny and evolution. AB - The elucidation of complete genomic sequences from a wide variety of retroviruses and retrotransposons has allowed the construction of sequence-based phylogenies that reveal their evolutionary history. True retroviruses, whether exogenous or endogenous, tend to cluster into four major groups. Not only is there no distinction between exogenous and endogenous viruses, but their evolutionary limb lengths on the phylogenetic trees are comparable. This can be taken as evidence favoring a dynamic equilibrium balancing a constant invasion of germlines by infectious retroviruses on the one hand, with subsequent escape of endogenous viruses to alternative hosts on the other. Retroviruses share a common ancestry with a wide variety of retrotransposons and other reverse transcriptase-bearing entities. One of these retrotransposon groups, the Gypsy group, resembles the Moloney mouse group of retroviruses much more closely than it does other retroviruses. The simplest explanation is that the evolutionary rate of the retrotransposon is much slower than the retrovirus rate and that among the retroviruses the Moloney mouse group has been evolving more slowly than the other three groups, leaving the two short-limbed taxa more similar. The alternative explanation that these two groups actually shared a common ancestor more recently than has either with the other retrovirus groups is not supported by residue-by residue character assessment. PMID- 2203608 TI - Retroviral proteinases. PMID- 2203609 TI - Retrovirus envelope glycoproteins. PMID- 2203610 TI - Integration of retroviral DNA. PMID- 2203611 TI - The structure and function of retroviral long terminal repeats. PMID- 2203612 TI - A sound idea. PMID- 2203613 TI - Inflammatory markers in bronchoalveolar lavage and in bronchial biopsy in asthma during remission. AB - Bronchoalveolar lavage and BB were performed in 13 asthmatic and six healthy subjects to characterize cellular markers of inflammation in BAL and BB; to compare cellular profile of BAL with cell infiltration in BB; to examine the relationship between bronchial responsiveness and markers of inflammation in BAL and BB. Eosinophils and mast cells were increased in BAL in asthmatic subjects; eosinophils were positively correlated with neutrophils and mast cells. Epithelial shedding was present in nine asthmatic and five control subjects. Intraepithelial cells and cells in submucosa were increased in asthmatic subjects. Eosinophils and intraepithelial mast cells were higher. Thickened basement membrane was associated with more marked cell infiltration in submucosa. Ciliated cells in BAL relate to intraepithelial cells; cells in BAL broadly reflect cell infiltration of submucosa. In the asthmatic group, the degree of bronchial responsiveness correlated with ciliated cells in BAL and with intra epithelial cells in BB. Marked airway inflammation is associated with stable asthma; inflammatory changes within bronchial epithelium may be linked to the development of bronchial hyperresponsiveness. PMID- 2203614 TI - Endoscopic ultrasound examination for mediastinal lymph node metastases of lung cancer. AB - Among patients with primary lung cancer who were admitted to the National Cancer Center Hospital from July 1987 to April 1988 for surgical treatments, 132 underwent preoperative transesophageal endoscopic ultrasound examination (EUS) on mediastinal lymph nodes. Of the 132 patients, 101 were pathologically evaluated and studied in this article. A GF-UM2 radial scanner with 7.5-MHz (Olympus Co Ltd) was used for image examination. The lymph nodes were diagnosed as positive for metastasis when they had thickened images, clear contours, and low echoing images of fusion or lobulation. The results obtained from 509 sites were as follows: sensitivity, 53.6 percent; specificity, 97.5 percent; positive predictive accuracy, 77.1 percent; negative predictive accuracy, 93.1 percent; and overall accuracy, 91.6 percent. The sensitivity rate was 80.6 percent excluding the result of the right superior mediastinal lymph nodes that were difficult to examine for anatomic reasons. Although EUS was considered to be an excellent method in diagnosing lymph node metastases, it had a blind angle in the field. More accurate diagnoses of mediastinal lymph node metastases could be achieved by using EUS and computed tomography (CT) together. PMID- 2203615 TI - Association of MS Pi phenotype with airway hyperresponsiveness. AB - Asthmatic families (AFs) and normal families (NFs) were studied to determine the relationship between bronchial hyperresponsiveness and alpha 1-antitrypsin protease inhibitor phenotype. We studied IgE levels, skin test scores, and methacholine sensitivity. In both the AF and NF groups, the subjects with the MS phenotype had significantly greater methacholine-induced bronchial hyperresponsiveness sensitivity than the MM and MZ subjects. These findings suggest that the S allele may be associated with bronchial hyperresponsiveness. PMID- 2203616 TI - Noninvasive options for ventilatory support of the traumatic high level quadriplegic patient. AB - The ventilation of 25 ventilator-dependent traumatic quadriplegic patients was supported by noninvasive means of ventilatory assistance. Twenty-four of the 25 were initially managed by endotracheal intubation, and 23 of these went on to tracheostomy intermittent positive pressure ventilation before being converted to NVA. Seventeen of the 23 patients had their tracheostomies closed. This included three patients with no significant free time except with the use of glossopharyngeal breathing. Seven of the 25 patients who used NVA for at least one year with no significant free time have employed NVA for a mean of 7.4 +/- 7.4 years (1 to 22 years). Mouth IPPV was the most common form of NVA used both during the daytime and overnight. The wrap ventilators, intermittent abdominal pressure ventilator, and GPB were also employed for long-term respiratory support. It was concluded that, in general, because of their youth, intact mental status and bulbar musculature, and absence of obstructive lung disease, patients with traumatic high level spinal cord injury are candidates to benefit from these techniques. PMID- 2203617 TI - Efficacy of atropine methylnitrate alone and in combination with albuterol in children with asthma. AB - The bronchodilator effect of nebulized AMN, albuterol and their combination was evaluated in 16 steroid-dependent asthmatic children. In phase 1, maximal bronchodilation was determined by dose-response studies on separate days. Maximal bronchodilator dose of each drug was administered either alone or in combination during phase 2. In phase 1, 0.11 +/- 0.01 mg/kg of albuterol and 0.03 mg/kg of AMN produced maximum bronchodilation. In phase 2, the peak response to albuterol occurred within 30 min and to AMN, at 60 min. Maximal FEV1 achieved after AMN was 90 percent of the maximal achieved after albuterol. AMN FEV1 response was better than for placebo for 3 h; that for albuterol was better for 4 h. Combination therapy produced a peak response similar to that of albuterol but was better than albuterol by 6 h. Thus, the maximum bronchodilator effect of AMN is less than that of albuterol in asthmatic children, but the combination may extend the period of bronchodilatation. PMID- 2203618 TI - Attenuating effect of a thromboxane synthetase inhibitor (OKY-046) on bronchial responsiveness to methacholine is specific to bronchial asthma. AB - To determine whether the involvement of thromboxane A2 in bronchial hyperresponsiveness (BHR) is specific to asthma, we examined the effects of a selective inhibitor of thromboxane synthetase (OKY-046) and a cyclooxygenase inhibitor (indomethacin) on bronchial responsiveness to methacholine in normal subjects and patients with chronic bronchitis, diffuse bronchiectasis, and intrinsic bronchial asthma. The provocative concentration of methacholine producing a 20 percent fall in forced expiratory volume in 1 s (PC20-FEV1) was measured before and after oral administration of OKY-046 (2,600 mg over four days) and indomethacin (450 mg over three days) in ten normal, ten bronchitic, nine bronchiectatic, and eight asthmatic subjects, respectively. Baseline values of FEV1 and forced vital capacity (FVC) were not altered by OKY-046 or indomethacin. The geometric mean value of PC20-FEV1 increased significantly (p less than 0.005) from 1.78 to 4.27 mg/ml after OKY-046 in asthmatic subjects, but not in normal, bronchitic, or bronchiectatic subjects. On the other hand, PC20 FEV1 increased significantly (p less than 0.005) from 2.19 to 8.13 mg/ml after indomethacin in bronchiectatic subjects, but not in normal, bronchitic, or asthmatic subjects. We conclude that the involvement of thromboxane A2 in BHR may be specific to asthma, and bronchial responsiveness of bronchiectasis may be potentiated by inflammatory release of bronchoconstrictor prostaglandins except for thromboxane A2. Further studies using thromboxane A2 receptor antagonists are needed to confirm the conclusion. PMID- 2203620 TI - Myocardial oxygen supply and demand. AB - The supply of oxygen to the myocardium is determined by coronary blood flow and oxygen carrying capacity. Coronary blood flow is a dynamic process modulated via multiple parameters. Cardiac metabolism is also affected by several factors. Under normal physiologic conditions, the demand is easily met by the supply of oxygen. In fact, there is a significant reserve on the supply side. Under certain pathologic states such as coronary artery disease, the supply of oxygen may be exhausted and an imbalance between supply and demand occurs which is translated into ischemia. The area of myocardium most susceptible to ischemia is the subendocardium due to mechanical and metabolic forces. In therapy of coronary artery disease, attention should be directed to directional changes in factors influencing supply and demand to improve blood flow to the most susceptible area. PMID- 2203619 TI - Esophagoatrial fistula with previous pericarditis complicating esophageal ulceration. Report of two cases and a review of the literature. AB - Sixteen cases of nontraumatic left atrial-esophageal fistulas have been reported previously. These fistulas usually result from chronic peptic esophagitis or cancer. The diagnosis is suggested by the triad of chronic dysphagia, hematemesis, and acute neurologic signs. There may be cardiac manifestations such as pericarditis, atrial fibrillation, or shock. An unusual feature of these fistulas is systemic embolization of food, air, or septic necrotic debris which may result in sudden central nervous system symptoms. All reported cases resulted in death due to hemorrhage, although there was often a variable time interval between the onset of hematemesis and the patient's death. The authors report two additional cases in which an episode of pericarditis preceded fistula development. Based on these 18 cases, the spectrum of esophagoatrial fistulas is reviewed, as well as the signs which may herald fistula development. PMID- 2203621 TI - Has the treatment of asthma improved? PMID- 2203622 TI - Catamenial pneumothorax. PMID- 2203623 TI - Neutrophil recruitment in the respiratory tract of a patient with plasma cell granuloma of the lung. AB - A 69-year-old woman had plasma cell granuloma of the left middle lobe of the lung. Her symptoms and roentgenologic findings improved with antibiotic treatment. Before treatment, the number of neutrophils and NCA were markedly increased in BAL fluid obtained from the affected region of the left lung and moderately increased in BAL fluid obtained from the nonaffected region of the right lung. The number of neutrophils, the NCA as well as the contents of C5 and C5a des Arg (neutrophil chemotactic factors) in the BAL fluids from both these regions decreased during treatment. These findings suggest that plasma cell granuloma was due to chronic immune and inflammatory reactions in the lung, that neutrophils are involved in development of the symptoms and signs of this disease, and that neutrophil chemotactic factors, including complement-derived factors, are important in neutrophil recruitment at the lesion and in nonaffected parts of the lung. PMID- 2203624 TI - [The history of dentistry through Western painting. 3. The 19th and 20th centuries]. PMID- 2203625 TI - [Impressions for removable partial dentures]. PMID- 2203627 TI - [High speed aspiration technic at the European level]. PMID- 2203626 TI - [Ampliative effectiveness on a new endodontic contra-angle, Excalibur]. PMID- 2203628 TI - [The dentist Audibran and the judgement of the Court of Cassation 1827 and 1846. A contention over the law of Ventose 19 year 11]. PMID- 2203629 TI - [1789: the grievance records of physicians and surgeons]. PMID- 2203630 TI - [Oral manifestations of lichen planus. 2. Histological, immunological and therapeutic aspects]. PMID- 2203632 TI - [The "hooker" of the Champ-Chalon necropolis]. PMID- 2203631 TI - [Complete denture with liquid cushion]. PMID- 2203634 TI - [The taper of canal walls in endodontics: a therapeutic requirement]. PMID- 2203633 TI - [Fundamental principles of mechanized endodontics]. PMID- 2203635 TI - Use of avidin-biotin-peroxidase complex in immunoassay for detecting cholera toxin. PMID- 2203636 TI - Isolation and characterization of temperature-sensitive mutants of Saccharomyces cerevisiae. AB - Temperature-sensitive (ts) mutants of Saccharomyces cerevisiae Y-196 were isolated by UV irradiation and/by EMS treatment. There were 163 ts mutants isolated from 66,957 colonies. These mutants were designated as AMY-1 to AMY-163. These ts mutants grew normally at 30 degrees C, but did not grow at 38 degrees C. In an auxanographic study, we showed that AMY-46 was an absolute ts mutant, while AMY-10, AMY-15, AMY-16, AMY-49, AMY-66, AMY-88, AMY-114, AMY-126, AMY-127, AMY 129, AMY-136, AMY-150, AMY-157, AMY-158, AMY-159, AMY-161, and AMY-162 were auxotrophic ts mutants except AMY-16 had cell size 2-42% larger than that of the wild type. Cell aggregation phenomenon was found when the ts mutants were cultivated at 30 degrees C to stationary phase then cultured at 38 degrees C for 4 hr. The budding numbers at 30 degrees C were less than that at 38 degrees C. Mutant AMY-49 had the highest budding number. There was a positive correlation between the growth rate and the average budding number. However, there was a negative correlation between the growth rate at 30 degrees C and the length of long axis of cell or the size of cell. PMID- 2203637 TI - Survival of Aeromonas hydrophila and Escherichia coli in aquatic environments. AB - Survival of Aeromonas hydrophila and Escherichia coli in distilled water, pond water and effluents of anaerobic digesters were examined. Survival capabilities of A. hydrophila in various aquatic systems were similar to E. coli except in the raw effluents of anaerobic digesters, where A. hydrophila survived significantly better than E. coli for 6 days. Pathogens such as Staphylococcus aureus, Salmonella enteritidis and Vibrio cholerae were readily killed in the raw effluents of the anaerobic digester. Results explain why A. hydrophila were so numerous in many fish ponds examined in Taiwan. A. hydrophila may also be recommended as a supplemental index of fecal pollution of water supplies. PMID- 2203638 TI - [Acute pain in surgery. Clinical significance, methods for measuring and therapy]. PMID- 2203639 TI - [Current concepts in the development and treatment of pain]. PMID- 2203640 TI - [Indications and methods of pain treatment from the neurosurgical viewpoint]. PMID- 2203641 TI - [Significance of sonography of the breast for surgical treatment of breast cancer]. AB - In a prospective study of 119 patients with breast carcinoma the value of ultrasonography for surgical therapy was compared with the value of clinical results and mammography. The tumor localization (in 96.8%) and the exact preoperative staging following the pTNM-system (tumor size in 85.8%, lymph node involvement in 77.2%) were better predicted by ultrasonography than by mammography and clinical examination. Especially the multicentric-multifocal carcinomas (20 of 29 cases) were better detected. Preoperative ultrasonography especially improves planning a conservative management of breast cancer. PMID- 2203642 TI - [Repair of recurrent inguinal hernia. Tactics, technic and results]. AB - Based on 301 surgical repairs of recurrent groin hernias perioperative management and recommended techniques for preparation and repair of various kinds of recurrent hernias are presented. Follow-up examinations could be performed on 175 patients, representing 88.8% of 197 patients who underwent surgery for recurrent hernias. Shouldice's technique for hernia repair proved to be the treatment of choice for recurrent groin hernias with a recurrence rate of 2.9% (5/175). Early postoperative complications occurred up to the 14th day following surgery. Frequently they could not be documented due to an average postoperative hospitalization period of 6.2 days only. The rates of postoperative complications were 8.1% prior dismission and 12.6% within two weeks after the operation respectively. PMID- 2203643 TI - [Traumatic bilateral renal artery occlusion. Case report and review of the literature]. PMID- 2203644 TI - [Para-pancreatic dermoid cyst]. PMID- 2203645 TI - Experimental and clinical chronocardiology. AB - Recent advances of the chronobiologic approach to experimental and clinical cardiology was reviewed. First, the maximum entropy method (MEM) was introduced as one of the statistical methods analyzing the circadian periodicity. The MEM power spectrum showed a remarkable resolution property. It will play an important role in chronocardiology in cooperation with the cosinor method. Secondly, recent investigations of the relationship between sleep states and cardiac arrhythmias were mentioned from the viewpoints of both experimental and clinical chronocardiology. Next, recent remarkable advance on myocardial ischemia was reviewed. A marked circadian rhythm in the frequency of myocardial infarction onset and sudden cardiac death has been observed. Lastly, a reference has been made to the recent development of ambulatory BP monitoring. A chronobiologic approach to the analysis of time-series data in cardiology will lead to many advantages in clinical practice. PMID- 2203646 TI - Scale-up of free flow electrophoresis: I. Purification of alcohol dehydrogenase from a crude yeast extract by zone electrophoresis. AB - The potential and limitations in scaling-up free-flow electrophoresis, with emphasis on zone electrophoresis, are demonstrated. Purification of alcohol dehydrogenase (ADH) from a crude yeast extract was chosen as a model for an industrial approach to enzyme purification. In zone electrophoresis the separation quality strongly depends on the pH and conductivity of the background electrolyte, its residence time and flow rate, as well as the applied voltage. Optimization of these parameters resulted in a purification factor of 5.3 and a yield of 96% ADH, using a Tris/HCl buffer, pH 8.0, and a conductivity of 1 mS/cm, with a residence time of 10 min at 500 V. The loading capacity of the method for a laboratory-sized free-flow electrophoresis apparatus was limited to a sample throughput of about 0.4 g/h. By increasing the chamber dimensions it was possible to purify the enzyme by a purification factor of 4.7 and a yield of 93% ADH, at a throughput of about 1 g total protein/h. By simultaneously applying the sample at 3 input positions the throughput could be increased to 2.75 g/h with a purification factor of 4.7 and an overall yield of 90%. PMID- 2203647 TI - Scale-up of free-flow electrophoresis: II. Purification of alcohol dehydrogenase from a crude yeast extract by field step electrophoresis and combined field step zone electrophoresis. AB - Results of the purification of alcohol dehydrogenase (ADH) by field step electrophoresis and combined field step-zone electrophoresis are presented. In field step electrophoresis, optimization of voltage, residence time and pH of the sample solution led to a maximal purification factor of 2.8 and a yield of 89% ADH. The limit of loading capacity was reached at a protein concentration of the sample solution of approximately 4 g/L, allowing a maximal throughput of 1.14 g/h with a yield of 86% and a 2.8-fold purification in the Elphor VaP 22 apparatus. With a production scale apparatus a throughput of 2.07 g/h without any loss of separation quality could be achieved. By introducing the sample solution into the separation chamber through 3 inlets, simultaneously, the throughput was increased to 3.2 g/h with a purification factor of 2.7 and a yield of 82% ADH. For the combined field step-zone electrophoresis method a maximum purification factor of 3.6 and a yield of 80% ADH were achieved. The loading capacity was limited to a 4.13 g/L protein concentration of the sample solution, resulting in a throughput of 440 mg/h. Injecting the sample solution simultaneously into 3 inlets resulted in a maximum throughput of 1.92 g/h with 3.1-fold purification and a yield of 80% ADH. Zone electrophoresis, field step electrophoresis and a combination of both are compared with respect to resolution, throughput and the application potential in a protein purification scheme. A scale-up to 3 g/h is possible in zone electrophoresis and field step electrophoresis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203648 TI - Breakage--reunion and copy choice mechanisms of recombination between short homologous sequences. PMID- 2203649 TI - Minimizing blood usage after open heart surgery. Nurses play a key role. PMID- 2203650 TI - A review of sulphites in foods: analytical methodology and reported findings. AB - Sulphites in various forms have been added to foods for centuries. Their use became an issue of concern when certain sensitive individuals exhibited adverse reactions to sulphite residues in foods. Analytical methods were developed to monitor these compounds at the regulatory limit of 10 ppm. In this report, analytical methods for determining sulphites in foods are reviewed, along with a critique of their chemistry and procedural schemes. An assessment of the key features of each method category is presented together with some comparative data. The classification scheme used is based upon the fact that determination of the sulphite content of a food is influenced more by the treatment and cleanup of the test solution than by the final determinative step. Based on a 60-year database, the Monier-Williams procedure still remains the method of choice. PMID- 2203651 TI - Ethyl carbamate (urethane) in alcoholic beverages and foods: a review. AB - This IUPAC review covers the earlier studies of the 1970s on the analysis, occurrence and formation of ethyl carbamate (EC) in foods and alcoholic beverages, as well as the more extensive publications that have appeared since the renewed interest in EC in early 1986. In these latter studies, updated analytical procedures, including solid-phase extraction, capillary gas chromatography and mass spectroscopic detection, have become commonplace. These analytical methods are employed for regulatory and data-gathering purposes and provide extensive information on the occurrence of EC, much of which is presented in review. Distinct theories on the sources of EC, mechanisms for its formation and steps required to reduce its levels in stone-fruit brandies, wines and whiskies are summarized. These studies suggest separate pathways of EC formation for each of the three commodities. PMID- 2203653 TI - [T-Scan. Applied potential. Experimental verification]. AB - The Authors have tried to underline the characteristics and limits of T-Scan so as to provide an aid for the reliable usage of the instrument and avoid possible erroneous interpretations of the given data. PMID- 2203652 TI - [Oral pathology of pscyhosomatic origin. Review of the literature]. AB - Emotional stress is one of the etiologic or anyway predisposing factors involved in a lot of oral pathologies. In fact, relations between stress effects and frequent diseases such as gastric ulcer or ulcerous colitis are today wellknown by everyone. Theories about a relation between this kind of etiology and tumours are only reported by some Authors and are at the level of hypotheses. Mouth is very weak in these situations, owing to its great interest as primary erogenous zone, and for this reason we find frequently oral pathologies in relation with psychosomatic medicine. In this report we tried to give a good help to the study of these diseases and to find an easy classification to use (really it is an hard work to do due to the variety of this numerous illnesses). PMID- 2203654 TI - [Biocompatibility of dentinal adhesive systems in conservative dentistry]. AB - Several studies have been published on "in vitro" and "in vivo" evaluations on pulpal and dentin effects of new dentinal bonding agents. The present study analyses the current status of biocompatibility of these materials. It has been suggested that a good biocompatibility it is only possible if no bacteria penetration and microleakage are present along dentinal walls and around restoration cavity. Finally it is not well defined the importance of smear layer removal from cut dentin surface. PMID- 2203655 TI - [Computerized occlusal verification in denture frames]. AB - Partial removable prosthesis must foresee masticatory force distribution on all dental arch, with occlusal contacts uniformly distributed on natural and artificial teeth. These dental contacts must have the same intensity and they must happen in the same time, rispetting the gnathology laws. In this work it is investigated the possible utilization in partial removable prosthesis of T-Scan. PMID- 2203656 TI - [Reimplants and implants. Presentation of 2 technics]. PMID- 2203657 TI - [Pulpal-periapical response to canal medication with Ca(OH)2]. AB - This study consisted of biopsies of teeth and root tips removed after Ca(OH)2 therapy. The teeth were clinically intact or exposed to caries, trauma, and/or iatrogenesis. Following the therapy most of the canal walls were clean, but the canals contained varying amounts of pulp tissues, debris and Ca(OH)2 particles. In one case microrganisms were present in the apical part of the canal, but not beyond the foramen. The Ca(OH)2 therapy was efficient for its purpose. PMID- 2203658 TI - Familial pemphigus vulgaris. AB - Familial pemphigus vulgaris was found in a Jewish woman and her son who developed the disease within a period of 18 months from one another. HLA typing was performed in the mother and son as well as in the unaffected father and sister. Examination of the HLA antigens in this family indicates that there may be different variants of DR4, DQw3 and that one of them carried by the mother and son as part of the haplotype A30, B18, DR4, DQw3 is associated with pemphigus vulgaris. Our findings are in favor of the concept that particular polymorphic residues of class II major histocompatibility molecules are correlated with disease susceptibility. PMID- 2203659 TI - Psoriasis related to angiotensin-converting enzyme inhibitors. AB - Two mechanisms have been proposed for the pathogenesis of eruptions induced by angiotensin-converting enzyme (ACE) inhibitors: (1) an allergic, immune-mediated reaction and (2) a pharmacologic, dose-dependent response. Two cases of palmoplantar psoriasis are presented, which can be attributed to the induction (case 1) and exacerbation (case 2) of ACE inhibitors. The first patient developed his eruption 2 months after he had received captopril, probably as a result of an allergic immunologic mechanism. This has been based mainly on circumstantial evidence and is further strengthened by the positive result of the mast cell degranulation test. The second patient developed an atenolol-induced, mild plantar psoriasis. She experienced a dramatic flare-up of her psoriatic lesions shortly after she had received an ACE inhibitor. It is suggested that her reaction occurred as a result of the enalapril-induced augmentation of kinin levels in the skin. These 2 patients represent deductive and unusual examples of the two different mechanisms that are responsible for the cutaneous complications of ACE inhibitors. PMID- 2203660 TI - Classification of intractable diarrhea in infancy using clinical and immunohistological criteria. AB - Several experimental studies have demonstrated that activated intestinal T cells can induce villous atrophy. This observation led us to examine the possible role of activated T cells in the pathogenesis of intestinal lesions in a group of 13 children with intractable diarrhea and villous atrophy of unknown origin. Immunohistochemical study showed signs of intestinal mononuclear cell activation in seven patients. These signs included a marked increase in the number of mucosal T cells, mainly TCR alpha beta+, the appearance of lamina propria interleukin-2-receptor-bearing cells, and an increased expression of HLA-DR antigens by enterocytes. No local cause of intestinal T-cell activation was found. However, four out of seven patients had extradigestive symptoms of autoimmunity, suggesting that the intestine might also be the site of an autoimmune reaction responsible for the epithelial lesions. In these patients, presence of crypt necrosis and colic extension of the lesions suggested poor prognosis. In contrast, in six other patients, no immunohistochemical evidence of mucosal T-cell activation was obtained. In the latter cases, analysis of clinical data favored the hypothesis of a primary inborn defect of enterocyte differentiation. PMID- 2203661 TI - Immunohistochemical localization of ethanol-inducible P450IIE1 in the rat alimentary tract. AB - To determine whether P450IIE1, a microsomal P450 enzyme inducible by ethanol in the liver, is also present and inducible in the alimentary tract, corresponding frozen tissue sections were prepared from rats pair-fed liquid diets containing 36% of total calories as either ethanol or carbohydrate (control) for 3 weeks. Immunohistochemical staining was performed using the peroxidase-antiperoxidase method after tissue sections were reacted with antibody against human P450IIE1. In control animals, immunoreactive P450IIE1 was detected only in duodenal and jejunal villous cells. After ethanol treatment, the content of P450IIE1 increased in duodenal and jejunal villi, and the enzyme was now also found in squamous epithelial cells of the cheek mucosa, tongue, esophagus, and forestomach, and in surface epithelium of the proximal colon. P450IIE1 was neither expressed nor induced by alcohol in the epithelium of stomach fundic and antral mucosa, ileum, distal colon, and rectum. When considered together with the xenobiotic activation properties of P450IIE1, these results may partly explain why alcohol abuse is a risk factor for cellular damage or cancer or both in those alimentary tract tissues in which P450IIE1 is inducible by chronic ethanol intake. PMID- 2203662 TI - A double-blind, controlled trial of bioflorin (Streptococcus faecium SF68) in adults with acute diarrhea due to Vibrio cholerae and enterotoxigenic Escherichia coli. AB - The therapeutic efficacy of Bioflorin (Streptococcus faecium SF68; Gipharmex, Milan, Italy) in acute watery diarrhea was evaluated in 183 Bangladeshi adults. Vibrio cholerae organisms were isolated from stool cultures in 114 patients, and enterotoxigenic Escherichia coli organisms were isolated in 41. In addition to IV rehydration, patients were randomly assigned to receive either capsules of Bioflorin containing 1 X 10(9) of live SF68 or capsules of placebo containing killed SF68 once every 8 hours for 3 days. No other drugs were allowed during this period. Bioflorin was well tolerated. It is concluded that Bioflorin has no demonstrable antidiarrheal property in adults with acute diarrhea due to V. cholerae or enterotoxigenic E. coli infection. PMID- 2203663 TI - Gastroesophageal endoscopic features in cirrhosis: comparison of intracenter and intercenter observer variability. PMID- 2203664 TI - Detection of hepatitis B virus antigens in liver tissue. A relation to viral replication and histology in chronic hepatitis B infection. AB - The expression of hepatitis B virus antigens was studied by double staining liver tissue with appropriate antisera and correlated with serum hepatitis B viral DNA and histology in 28 patients with disease related to chronic hepatitis B virus infection. The cellular localization of hepatitis B core and hepatitis B e antigens generally coincided, but there were important differences at a subcellular level. Thus, hepatitis B e antigen was detected in nuclei and/or cytoplasm but strong cytoplasmic hepatitis B e antigen was associated with a high serum hepatitis B viral DNA (P = 0.0017) but not with active liver disease. Hepatitis B core antigen could also be detected in nuclei and/or cytoplasm, but strong cytoplasmic hepatitis B core antigen expression, exceeding that of hepatitis B e antigen, was associated with active liver disease (P = 0.041) and not with serum hepatitis B virus DNA. The proportion of hepatocytes expressing hepatitis B surface antigen correlated inversely with the serum titer (P = 0.0017), whereas hepatitis B surface and nucleocapsid antigens were usually expressed independently. The data support the hypothesis that cytoplasmic hepatitis B core antigen and not hepatitis B e antigen is the target for immune system-mediated cytolysis of hepatocytes. Cytoplasmic hepatitis B e antigen is not associated with liver damage but is instead associated with high levels of hepatitis B virus replication. PMID- 2203665 TI - [Blood transfusion service during World War II]. PMID- 2203666 TI - [Therapeutic effectiveness of the Russian drug reaferon in hairy cell leukemia]. AB - The results of the clinical trial of Soviet reaferon in 16 patients with hairy cell leukemia have been presented. Clinicohematological effect of the drug has been ascertained in 62% of the cases. It has been established that the agent is well-tolerated and produces a good antitumor effect. Doses and regimens of the drug administration to hairy-cell leukemia patients have been developed. PMID- 2203667 TI - [Possibilities of differential diagnosis of B-cell chronic lymphoproliferative diseases using monoclonal antibodies]. AB - Immunological phenotyping of lymphoid cells of the peripheral blood and, in some cases, of the lymph nodes and spleen was conducted in 41 patients with B-cell chronic lymphoproliferative diseases. Four monoclonal antibodies (MCA) were used in the immunofluorescence test, the results of which were analyzed by means of microscopy and flow cytofluorometry as well as by rosette-formation with mouse red blood cells. Varying expression degree has been shown by two B-cell differentiation antigens identifiable with MCA CD24 and CD20 on lymphoid cells of patients with typical B-cell chronic lymphoid leukemia (B-CLL) and lymphosarcoma. The varying expression degree is characteristic of small lymphocytes and transformed lymphoid cells in both the diseases. Differences in the number of cells expressing CD 5 (T1) antigen in B-CLL and lymphosarcoma, as well as correlation of this marker with EM-receptor expression have been recorded. The possibilities of using the results of the study for the differential diagnosis of chronic B-cell lymphoproliferative diseases, including B-CLL and B-lymphocytic lymphoma, and for investigation of B-cell lymphoproliferative disease pathogenesis have been discussed. PMID- 2203669 TI - [Automated system of quantitative assessment of risk of disorders of the functional state of the liver in prophylactic examinations]. AB - The article presents the structure and constituent elements of the algorithm of liver disorders' assessment (ALDA). The latter was designed to be applied at the initial stage of comprehensive prophylactic medical examinations of workers carried out for an early risk-factor quantitative assessment of functional disorders of the liver. The main results of the ALDA approbation are given account of, which demonstrated a high level sensitivity and specificity of the algorithm and its applicability to most USSR-produced computers. PMID- 2203668 TI - [Analysis of fibrinogen, fibrin-monomer complexes, fibrin-fibrinogen degradation products and plasminogen levels in the capillary blood]. PMID- 2203670 TI - Proposed legislation would blunt area wage index changes. AB - Legislation introduced in Congress will blunt the dramatic changes in Medicare payments to hospitals resulting from the area wage index update. The legislation calls for the new index values to be phased in over the next two years instead of taking full effect on Oct. 1. However, the legislation will not alter the fact that hospitals in some market areas will be big winners, while those in other areas will be big losers. PMID- 2203671 TI - Report: hospitals need more sophisticated planning efforts. AB - Sophisticated planning efforts are increasing among hospitals. However, hospital planners and marketers still have far to go before they can match their counterparts in industry. This is according to a report on hospital planning recently released by the Society for Healthcare Planning and Marketing of the American Hospital Association, Chicago. PMID- 2203672 TI - Current status of urinary cytology in the evaluation of bladder neoplasms. AB - Pathologic examination of urinary specimens is increasingly recognized as an essential component of detection and monitoring for patients with bladder neoplasms. Among the available techniques, urinary cytology is the most useful. The current status of urinary cytology can be summarized as follows: 1. The demand for urinary cytology is steadily increasing as clinicians have realized the limitations of cystoscopy and even biopsy for monitoring bladder cancer patients, especially those having carcinoma in situ or receiving topical therapy. 2. Urinary cytology is currently an essential procedure for monitoring all patients with urothelial neoplasms and, if consistently used, can actually decrease the frequency with which patients need to be subjected to cystoscopy. 3. Even in moderately experienced hands, urinary cytology can detect almost all high grade urothelial neoplasms. 4. The cytologic interpretation of low-grade transitional cell neoplasia requires expertise. These cells lack many of the features of malignancy, a source of confusion for the diagnostician but a positive factor for the patient since neoplasms composed of these cells are almost never aggressive. 5. The most useful type of urinary specimen for routine diagnostic interpretation is freshly voided, randomly collected urine. Catheterized specimens and bladder washings may yield more and better preserved cells, but no patient should be catheterized solely to obtain diagnostic material. 6. Preservation of urinary specimens in alcohols is not necessary unless prolonged storage is contemplated. Refrigeration to prevent bacterial growth and inhibit further cellular degeneration is required, however. 7. Cytologic details are best displayed with membrane filtration but other types of processing are adequate. The computer-programmed cytocentrifuge is currently most popular. 8. Optimal recognition of cytologic details requires some form of Papanicolaou staining; Romanovsky dyes are less desirable. 9. Urothelial cells with nuclear:cytoplasmic ratios of 1:2 or less should not be interpreted as malignant regardless of the degree of anaplasia of their nuclei. 10. Papillary aggregation is not a reliable feature of low-grade neoplasia in urinary samples. 11. Using appropriate criteria, the differential diagnosis of urothelial neoplasia versus the reactive/regenerative/reparative changes secondary to urinary stones can almost always be accomplished. 12. Alkylating agents such as Cytoxan, thio-TEPA, and mitomycin C produce characteristic but nonspecific changes in urothelial cells. These changes rarely mimic those of carcinoma. The diagnosis of urothelial neoplasia need not be confounded by previous treatment. 13. Flow cytometry and digitized image analysis are currently used for diagnostic interpretations of urinary specimens in selected centers. Their routine use must await further refinements in instrumentation and the formulation of more searching questions. PMID- 2203674 TI - Premature centromere division of a translocation-carrier autosome. AB - Premature centromere division of an aberrant chromosome 3 was found in a newborn girl with fetal hydrops and in her healthy father, both bearing a familial "balanced" 3p;19q translocation. The out-of-phase separation of a structurally abnormal chromosome may be of pathogenetic significance, the nature of which is not yet understood. PMID- 2203673 TI - Localisation of a dystrophin-related autosomal gene to 6q24 in man, and to mouse chromosome 10 in the region of the dystrophia muscularis (dy) locus. AB - We have localised a dystrophin-related autosomal gene called DMDL (Duchenne muscular dystrophy-like) to human chromosome 61q24 by in situ hybridisation. Using restriction fragment length polymorphism analysis in two mouse species, we have localised the homologous gene Dmdl in the mouse to chromosome 10 proximal to the Myb oncogene. A neuromuscular disease locus dystrophia muscularis (dy) has previously been assigned to this region of mouse chromosome 10. PMID- 2203675 TI - Automated perimeter for binocular suppression. AB - Scotomas associated with suppression amblyopia can appear or enlarge under binocular conditions. A device was designed to present an independent LED stimulus array to each eye while both eyes fixate together through beam splitters on a common background pattern. A computer-controlled field screening examination was designed to automatically plot suppression scotomas under binocular conditions. PMID- 2203676 TI - Expression of high-affinity IL-4 receptors on murine tumour infiltrating lymphocytes and their up-regulation by IL-2. AB - Since interleukin-2 (IL-2) and IL-4 act in concert to support the development of cytotoxic T lymphocytes (CTL) and the generation of antigen-specific tumour infiltrating lymphocytes (TIL), we investigated the interaction of these cytokines with an established TIL line. TIL proliferated in an additive fashion in response to suboptimal concentrations of IL-2 and various concentrations of IL 4. TIL possessed high-affinity IL-4 receptors whether cultured in recombinant IL 2 (rIL-2) or rIL-4, but cells cultured in rIL-2 had higher numbers of IL-4 receptors than cells cultured in rIL-4. When TIL were cultured in increasing concentrations of rIL-2, a dose-dependent enhancement in IL-4 receptor number was observed. The maximum induction of IL-4 receptor expression was achieved by 4 hr of incubation with rIL-2 and was completely blocked by cycloheximide. Other cytokines, such as rIL-1, recombinant tumour necrosis factor (rTNF), recombinant interferon-alpha (rIFN-alpha) and rIFN-gamma, had no effect on IL-4 receptor number. rIL-2 also up-regulated IL-4 receptors on CTLL-2, a murine CTL line. These data indicate that high-affinity IL-4 receptors exist on murine TIL and they can be up-regulated by IL-2. Our observation that IL-2 up-regulates IL-4 receptor may help explain the additive effects of these lymphokines on the proliferation of TIL and other cell lines. It may also help explain their co operative effects on the generation of antigen-specific TIL and the differentiation of CTL. PMID- 2203678 TI - R plasmids from clinical and environmental Klebsiella pneumoniae. AB - A total of 200 strains of K. pneumoniae, 150 from clinical and 50 from hospital environmental source were studied for antibiotic resistance pattern. The strains from clinical source showed higher incidence of drug resistance as compared to environmental strains. 50 clinical and 32 environmental multidrug resistant strains were tested for R plasmids. The biogroup 1 showed higher incidence of autotransferring and non autotransferring R plasmids. PMID- 2203677 TI - A monoclonal antibody, RbM2, specific for a lysosomal membrane antigen of rabbit monocyte/macrophages. AB - An anti-macrophage monoclonal antibody (mAb), RbM2, was produced using thioglycolate-elicited rabbit peritoneal macrophages as immunogen. The immunohistochemical approach revealed an intense reactivity of this mAb to macrophages, particularly those engaged in phagocytosis, in different organs and tissues, and to peripheral blood monocytes. Immunoelectron microscopy demonstrated reaction products of RbM2 in the lysosomes of macrophages and monocytes. This selective reactivity with the mAb was further confirmed in various experiments by endocytosis of Latex particles with different diameters or IgG-coated sheep erythrocytes. The results indicate that RbM2 recognizes a lysosomal membrane antigen of 50,000 molecular weight (MW). In contrast, dendritic cells, such as follicular dendritic cells (FDC) of lymphoid follicles, interdigitating cells (IDC) of lymphoid T zones, or epidermal Langerhans' cells, were not reactive with the antibody. Thus, RbM2 is useful not only in differentiating the phagocytic macrophages from the immunologically accessory dendritic cell populations but also in identifying lysosomes and their related structures in macrophages. PMID- 2203679 TI - A modified technique to process peripheral nerves for light microscopy. AB - A new technique is described to fix, paraffin embed and cut routine peripheral nerve biopsies for light microscopy. Buffered glutaraldehyde pH 7.4 is used as a common fixative for both light and electron microscopy. The nerve bits for LM are embedded in paraffin using the 'reverse embedding' method and blocks are trimmed to cut sections on the ultra microtome using glass knives. The uniformly thin sections can be utilised for any special stain and the good resolution of these thin sections facilitates better observation and documentation. PMID- 2203680 TI - Tuning free radical metabolism to kill tumor cells selectively with emphasis on the interaction(s) between essential fatty acids, free radicals, lymphokines and prostaglandins. PMID- 2203681 TI - Central role for vasopressin in cardiovascular regulation and the pathogenesis of hypertension. PMID- 2203683 TI - The (ir)relevance of short term studies. PMID- 2203682 TI - Role of macula densa in diuretics-induced renin release. AB - Diuretic therapy may enhance renin release by various mechanisms, principally contraction of extracellular fluid volume and its effects, including a fall in arterial pressure. Awake hydropenic or volume-expanded rats received diuretics (amiloride and hydrochlorothiazide) that are known inhibitors of NaCl transport beyond the macula densa; also the well-known Na(+)-K(+)-2 Cl- transport system inhibitor furosemide was administered. We also evaluated the effect of a dose of ethacrynic acid (a drug that shares the same mechanism of action as furosemide but is not diuretic in the rat). The direct action of the diuretics on renin producing cells was examined in isolated glomeruli; a rise in renin release was observed with the calmodulin inhibitor trifluoperazine (10(-5) M). Renin release in intact hydropenic rats was not altered by diuretic therapy, but furosemide increased plasma renin activity in hydropenic as well as in volume-expanded rats. This demonstrates the importance of furosemide inhibition of transport in the macula densa for its renin secretory action. None of the diuretics (amiloride, hydrochlorothiazide, ethacrynic acid, or furosemide) elicited changes in renin release from glomeruli (10(-6) to 10(-3) M); amiloride and hydrochlorothiazide (10(-4) to 10(-3) M) did not change renin release from slices, but 10(-3) M ethacrynic acid and furosemide increased renin secretion in this preparation. This suggests that an effect on the macula densa is essential in loop diuretic mediated renin release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203684 TI - Beta 2-microglobulin serum levels during dialysis: effect of cuprophan and serum osmolality changes. AB - New cuprophan dialysers were used in twenty, re-used dialysers in twelve dialyses and new dialysers in ten sequential ultrafiltrations. Serum beta 2-microglobulin (beta 2m) concentration was measured before and after all these procedures. Serum osmolality changes were compared with changes in serum beta 2m concentrations. These concentrations rose in dialyses with new and re-used dialysers, but remained unchanged during sequential ultrafiltration. beta 2m increased with serum hypo-osmolality, decreased with serum hyperosmolality and did not change during iso-osmolar dialysis. These results indicate that cuprophan membrane does not raise beta 2m concentration during dialysis. It is hypo-osmolality that is responsible for the increment of beta 2m in serum. PMID- 2203685 TI - An algorithm for approximating conditional probabilities. AB - When diagnostic programs are constructed within a probabilistic framework, it is often the case that computation of joint probabilities of exhaustive combinations of events is easy, but computation of the kind of conditional probabilities the user wishes to know, is hard. This paper describes a simple algorithm for computing the required values, and then suggests several heuristic optimizations that may enable suitable approximations to be obtained in a feasible time when the task is otherwise intractable. An account is given of a specific application of the method in the construction of a medical diagnostic program, which is described in more detail elsewhere. PMID- 2203686 TI - Computer-assisted teaching and learning in medicine. AB - Induced mainly by the increased spreading of personal computers in the last few years computer-assisted instruction (CAI) systems for medicine have been developed on a large scale. Proven structure principles are above all the simulation of patient management in a problem-orientated approach, the mathematical simulation of (patho-) physiological functions independent of particular patients and the separation of educational mode and scoring mode. There exists already a large choice in programs dealing with topics of internal medicine--especially cardiology--while operative disciplines are less represented so far. Programs accredited in the US for continuing medical education (CME) are usually of high quality as to medical contents. Other important quality criteria to be mentioned concerning simulation programs are algorithms of medical decision making, completeness and refinement of the medical knowledge base, software design and user interface. CAI is a unique tool to enhance clinical problem solving skills although--of course--it can by no means replace bedside teaching. PMID- 2203687 TI - Medical informatics: the substantive discipline behind health care computer systems. AB - The computer is rapidly becoming an interactive workstation for medical research and for clinical decision-making and it has become a preferred instrument for communication and documentation throughout health care. However, when the attempt is made to use the rigid conventions of information processing to impose order on the characteristically volatile and unpredictable phenomena encountered in the clinical setting, deep seated logical issues are uncovered. This challenge has generated the new field of Medical Informatics, one major goal of which is to formulate computer logics that can properly relate the idealized descriptions of disease, the rules for medical practice and the general guidelines for health care to the intricate diversities encountered in the care of individual patients. The Integrated Academic Information Management System (IAIMS) program of the National Library of Medicine provides the most ambitious environment for research in this new endeavor. PMID- 2203689 TI - Selection and characterization of human melanoma lines with different liver colonizing capacity. AB - Two human melanoma lines with low (HT168) and high (HT168-MI) liver metastatic capacity in immunosuppressed mice were selected in vivo from the A2058 cell line. After i.v. injection of the 2 tumor lines there was no significant difference either in the number of lung colonies or in the frequency and tissue distribution of extrapulmonary tumor deposits. These findings suggest that the selection in the spleen-liver system did not result in an overall increase in the metastatic potential of the melanoma cells, but rather that it represented an organ preferential selection. The HT168-MI cells did not acquire an increased growth rate in vitro or in vivo, suggesting that other phenotypic alterations are responsible for the enhanced metastatic capacity. The 2 tumor lines were characterized by similar expression of HLA-A,B,C, transferrin receptor and melanoma-associated proteoglycan antigen. HT168 contained more NGF receptor, while HLA-DR appeared only on HT168-MI cells. This human metastasis model could be useful in studying the mechanisms of liver metastasis formation, as well as in revealing possible new targets of antimetastatic therapy. PMID- 2203688 TI - K-ras mutations (codon 12) are not involved in down-regulation of MHC class-I genes in colon carcinomas. AB - Fifty-eight colorectal carcinomas were studied for HLA class-I antigen expression and for the presence of point mutations in codons 12 and 61 of the K-ras gene. Eight carcinomas were completely negative for class I by the APAAP technique. Analyses using the polymerase chain reaction (PCR) method, together with selective hybridization using mutation-specific synthetic oligonucleotides, demonstrated K-ras mutations in 14 cases (24.1%), all of them in codon 12. None of the mutations corresponded to the negative cases for class-I HLA antigen expression. We did not observe any correlation between K-ras mutations and the extent of tumor differentiation. PMID- 2203690 TI - Hormone sensitivity in vitro and in vivo of v-ras-transfected MCF-7 cell derivatives. AB - Human mammary carcinoma cell lines (MCF-7) were analysed for their hormone sensitivity before and after transfection with a v-Ha-ras oncogene or with a neomycin-resistance gene followed by selection in vitro or in vivo. Our aim was to test how the expression of the ras oncogene would influence the estradiol sensitivity of MCF-7 cells. In culture, MCF-7 cells expressing the viral p21 oncogene product, as compared to parental MCF-7 cells and their control derivatives, showed lower levels of a 67-kDa estrogen receptor. Progesterone receptors, however, remained sensitive to up-regulation by estrogens. The oncogene-expressing cells were less sensitive than all controls to stimulation of proliferation by 10(-8)M estradiol or to inhibition of proliferation by 2-CH3-4 OH tamoxifen, and this was not dependent upon the type of culture medium used. After s.c. or i.p. injection into female athymic nude mice, ovariectomized or left intact, the growth of MCF-7 cells expressing the ras oncogene product and of all control cells was sensitive to stimulation by estrogen supplementation. Conversely, cell lines derived from tumors generated with long latency in untreated athymic nude mice by v-ras-expressing MCF-7 cells showed efficient formation of quickly growing tumors in the absence of estrogen supplementation. No differences were observed in invasion and metastasis of the different MCF-7 cell types injected into athymic nude mice that were supplemented with estrogens or not. PMID- 2203691 TI - Inflammation and anti-tumor resistance. V. Production of a cytostatic factor following cooperation of elicited polymorphonuclear leukocytes and macrophages. AB - When Lewis tumor cells (3LL) included in a gel of polyacrylamide microbeads are injected into mice and recovered 1 day later, incorporation of 125I-UdR is strongly reduced. In contrast, no reduction is observed in irradiated mice. The cytostatic effect is non-existent in 6 hr-old granuloma (granulocytes 90%, macrophages 10%), but is maximal in 48 hr-old granuloma (granulocytes 50%, macrophages 50%). When 6 hr-old granuloma cells (which are not cytostatic) are incubated with bone-marrow-derived macrophages (BMs) (which are slightly cytostatic), considerable cytostasis against 3LL is observed, such an effect being strongly reduced if the 2 cell populations are separated. This suggests that close contact of live polymorphs with macrophages is necessary for full expression of cytostasis. No increase in cytostasis of bone-marrow macrophages is observed when BMs are incubated with a cell-free extract of freeze-thawed 6-hr old granuloma cells. Cell contact is not necessary between granuloma cells and 3LL since the cytostatic activity is found in the supernatant of incubated phagocytic cells. Cytostasis is also observed with B16, P815, J774 cells and normal mouse bone-marrow cells. An active cytostatic fraction has been purified from the supernatant of 48-hr-old granuloma cells following molecular filtration and HPLC. The cytostatic factor has a low molecular weight (400-500 daltons), is not a peptide and presents maximum absorption at 267 nm. PMID- 2203692 TI - Intravenous streptokinase in the management of a subset of patients with unstable angina: a randomized controlled trial. AB - We report the results of a randomized controlled trial of intravenous streptokinase in a subset of patients with unstable angina. Seventy-six patients were admitted with prolonged (more than 20 minutes) angina at rest of less than 3 weeks onset. Fifty-two patients continued to have more than 3 episodes of prolonged angina in 48 hours on medical therapy with metoprolol, isosorbide dinitrate, nifedipine and intravenous nitroglycerin. Forty-eight patients consented to enter the study and were randomized into two groups. The first group, of 24 patients, received 1.5 million units of streptokinase infusion and the second group, also of 24 patients, received a placebo. Pain relief within 48 hours was achieved in 19/24 (79.1%) patients after streptokinase infusion as compared to 9/24 (37.5%) of the controls (P less than 0.05). Approximately 90% (17/19) of patients responding to streptokinase therapy were relieved of chest pain within the first six hours as against none in the controls. The incidence of acute myocardial infarction within six months was 12.5% (3/24) in those receiving streptokinase and 25% (6/24) in the controls. Mortality at six months stood at 8.33% (2/24) in the treated patients and 16.6% (4/24) in the controls. Intravenous streptokinase thus appears to be of benefit in patients with angina at rest of recent onset which does not respond to conventional medical therapy. PMID- 2203693 TI - Endocarditis due to Streptococcus agalactiae: a favorable outcome with conservative treatment. AB - A case of infective endocarditis due to Streptococcus agalactiae was treated conservatively by means of cefotaxime sodium given intravenously at a dose of 1 g every six hours supplemented with gentamycin sulphate, also given intravenously, with the dose adjusted according to concentrations of the drug in the plasma. The treatment was successful. PMID- 2203694 TI - A "magic" aid for hypnosis and suggestion in crisis management: a brief communication. AB - Within the context of crisis management, in certain cases the transfer of a small object from therapist to patient has had positive outcomes. Examples of the use of this "magic" aid are provided with some background and a tentative rationale. Caution regarding its use is suggested. PMID- 2203695 TI - Psychopharmacology in patients with hepatic and gastrointestinal disease. AB - Psychotropic drugs often need to be prescribed to patients who also have pre existing gastrointestinal (GI) and/or hepatic disease. This paper addresses the effect of GI and hepatic disease on the pharmacokinetics of psychotropic drugs, the effect of psychotropic drugs on pre-existing GI and hepatic diseases, the adverse GI and hepatic effects of psychotropic medications, the effects of GI medications on mental status, and the potential drug interactions between commonly prescribed GI medications and psychotropic drugs. Drug selection and dosage modification based on these considerations should allow safe and effective psychotropic treatment for patients with pre-existing GI and/or hepatic disease. PMID- 2203697 TI - Implant-supported suprastructure design. PMID- 2203696 TI - Subclinical hypothyroidism: a review of neuropsychiatric aspects. AB - The authors review current information about the prevalence, causes, course, and consequences of subclinical hypothyroidism. There is evidence that subclinical hypothyroidism may be associated with cognitive dysfunction, mood disturbance, and diminished response to standard psychiatric treatments. Recommendations are presented for the screening, evaluation and treatment of patients in whom subclinical hypothyroidism may be contributing to neuropsychiatric dysfunction. PMID- 2203699 TI - Problems in the use of large data sets to assess effectiveness. AB - Large data sets are an attractive source of information for outcome assessment, but their use involves certain problems and risks. Data base evaluations are retrospective and unblinded; they often represent the result of multiple analyses of multiple endpoints, and it is difficult to identify the procedures used and analytic choices made because critical details are often omitted. While data bases can suggest problems and offer answers, they cannot prove them; data base analyses must be followed by trials. PMID- 2203698 TI - Use of data registries to evaluate medical procedures. Coronary Artery Surgery Study and the Balloon Valvuloplasty Registry. AB - Large registries have been used by the National Heart, Lung, and Blood Institute to evaluate a number of medical procedures. Two of these, the Coronary Artery Surgery Study (CASS) and the Balloon Valvuloplasty Registry (BVR), are described to illustrate potential problems in using registry data to compare medical procedures. PMID- 2203700 TI - What do mortality studies reveal about hospital volume, teaching status, and ownership? AB - Numerous recent studies use risk-adjusted patient mortality rates to measure hospital performance, focusing on such hospital characteristics as volume of patients, teaching status, and ownership. This article summarizes the empirical findings of these studies, critiques their methods and models, and offers recommendations for overcoming several obstacles to meaningful correlation of patient outcomes and provider performance. PMID- 2203701 TI - Peaks and pits of using large data bases to measure quality of care. AB - This review of the advantages (peaks) and problems (pits) of large data bases to study quality contrasts their suitability with randomized control trials. Researchers need to advise policymakers and others about when statistically significant differences in quality are also politically and socially significant and deserve responsible reactions. PMID- 2203703 TI - Using administrative diagnostic data to assess the quality of hospital care. Pitfalls and potential of ICD-9-CM. AB - Diagnostic information within administrative data bases is generally in the form of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. The purpose of this article is to introduce ICD-9 CM, to review its strengths and limitations, and to suggest ways that it can be used through administrative files for assessing the quality of hospital care. PMID- 2203702 TI - Use of insurance claims data in measuring quality of care. AB - This article discusses data that might be used for measuring quality of care, for health care administrative purposes, and for tracking the use of technologies. The advantages and limitations of administrative data banks for research purposes and some process-of-care and outcome analysis are noted. Three important obstacles to their use--reliability of diagnosis and service information, unique patient identifiers, and provider identifiers--are discussed briefly. PMID- 2203704 TI - Measuring health care effectiveness. Research and policy implications. AB - The implications of effectiveness research are far-reaching. Thus, the specification of a broad research agenda and the soundness of the underlying research methodologies and data bases are critical. This article discusses the quality of administrative data and the infrastructure supporting an ongoing effectiveness research effort. PMID- 2203705 TI - Ernest Amory Codman, M.D., and end results of medical care. AB - Ernest Amory Codman, M.D., was one of the most important figures in the history of outcomes research in medicine. While his contemporaries scorned his efforts to create systematic procedures to evaluate the end results of medical care, his work foreshadowed many of today's most pressing issues in technology assessment. This article traces Codman's career as an innovator and political gadfly at the Massachusetts General Hospital during the first three decades of this century, and examines the development and demise of his end-result system. PMID- 2203707 TI - [Goals and limits of spontaneous detection of unwanted drug side effects]. PMID- 2203706 TI - [Relevance of rapid availability of microbiological data: the basis for calculating antibiotic therapy]. PMID- 2203708 TI - [Preventive use of lithium in affective psychoses from the internal medicine viewpoint]. PMID- 2203709 TI - [Drug commission--experiences at a university clinic]. PMID- 2203710 TI - [Salmonella abscess of the neck in a 68-year-old patient with myasthenia gravis and thymoma]. PMID- 2203711 TI - Iodinated contrast media effects on extravascular lung water, central blood volume, and cardiac output in humans. AB - Intravascular contrast media produce pulmonary edema in one rat model, but not in dogs or pigs. In humans, pulmonary edema after contrast media is rarely diagnosed, but subclinical edema could be more frequent than believed previously. Therefore, the authors prospectively studied the effects of diatrizoate (n = 5) and ioxaglate (n = 5) on extravascular lung water, central blood volume, and cardiac output in ten patients undergoing routine radiographic procedures. Variables were measured by thermal-dye dilution before and every 5 minutes after completion of the procedure for four repetitions. Extravascular lung water and central blood volume did not change significantly, indicating that pulmonary edema or pulmonary congestion did not occur. Cardiac output was elevated by 10.6% immediately after the procedure, but returned to baseline during the 10 following minutes. The authors conclude from this preliminary study in a small number of patients that intraarterial contrast media (less than 1.5 g/kg body weight of iodine) did not produce pulmonary edema or pulmonary congestion, even at a subclinical level. PMID- 2203712 TI - A computer-assisted, interactive radiology learning program. AB - A computer-assisted adjunct to traditional radiology teaching files is described. The student is presented with an image and questions with multiple choice answers. The student's choice leads to additional presentations that reinforce correct responses and provide a critique of incorrect answers. The process is under the control of a teaching script. Requirements for the system included the ability to present high-resolution radiology images along with text; high capacity for storing teaching scripts and images; ease of use by students and authors of teaching scripts; and reasonable cost. A prototype program was written in C-language and run on an IBM PS/2 (IBM Corp., Armonk, NY) with DOS. The hardware also included a 30 megabyte disk drive, an IBM Image Adapter/A and a 14 inch IBM 8514 monitor operating at a 1024 X 768 X 8 bit resolution. Image acquisition was accomplished with a high resolution Pulnix video camera (Pulnix Corp., Tokyo, Japan), with an Imaging Technology (Imaging Technology Corp., Weston, MA) frame grabber, attached to an IBM PC/AT. All hardware is available commercially. A sample teaching file was constructed using a case of ischemic colon after a cecal volvulus. Students used the system and provided a critique. Results indicate that computer-assisted teaching programs can be a valuable addition to traditional teaching methods in radiology. PMID- 2203713 TI - 1990 Distinguished Scientific Achievement Award presented to Herman Cember. PMID- 2203714 TI - 1990 Founders Award presented to Jack M. Selby. PMID- 2203715 TI - 1990 Elda E. Anderson Award presented to William E. Kennedy, Jr. PMID- 2203716 TI - 1990 William McAdams Outstanding Service Award. PMID- 2203717 TI - 1990 National Registry of Radiation Protection Technologists Awards. PMID- 2203718 TI - [Current aspects of hyposensitization]. AB - Hyposensitation (HS) or immunotherapy has long been used to block the allergic response to inhaled allergens. Double-blind studies with a placebo arm have established the effectiveness of HS, especially in allergic rhinitis. The aim of HS is to achieve a better tolerance after exposure to inhaled allergens by subcutaneous injections of the relevant allergen extract in repeated doses of increasing concentrations. Although the clinical efficacy is obvious, the pathogenesis of HS is not yet fully understood. The HS must be used strictly in accordance with the guidelines of the European Academy of Allergology and Clinical Immunology (EAACI) with respect to therapeutic effect, side-effects, and cost for doctor and patient. The indications, relative and absolute contraindications, guidelines for the HS and the therapeutic monitoring of the patients during HS are outlined. In addition to the correct therapeutic regimen, a critical criterion is the quality and standardization of the allergen extracts. The recommendations of the International Union of Immunological Societies (IUIS) should be respected. Semi-depot extracts are preferred nowadays. The side-effects consist of local reactions, general reactions with urticaria, asthma, and even anaphylactic shock. The immediate therapy, precautions and drugs necessary to treat this life-threatening event are described. PMID- 2203719 TI - [Extracorporeal piezoelectric lithotripsy of salivary calculi. Initial clinical experiences]. AB - Piezoelectric lithotripsy was performed in 14 patients with salivary stones. None of the patients required anaesthesia, analgesics or sedatives. All of the salivary stones could be fragmented totally during the first lithotripsy procedure. Three months after treatment with extracorporeal shock waves all the patients were free of symptoms and in 7 out of 14 patients no concrement could be found by sonography. The piezoelectric lithotripsy of salivary stones had caused no serious side effects as proved by clinical, biochemical, sonographic and magnetic resonance imaging examinations. Extracorporeal piezoelectric lithotripsy is a new and promising non-surgical therapy for selected cases of sialolithiasis of the large salivary glands of the neck. PMID- 2203720 TI - The usefulness of ultrasonography in intracavitary radiotherapy using selectron applicators. AB - Uterine perforation can occur during the procedure of intracavitary insertions for the treatment of carcinoma of the cervix. If radiation treatment proceeds in the situation of inadvertent perforation, severe complication may result. The ultrasonographic studies of five patients with metal intrauterine applicators in situ are described. The applicator appeared as a linear echogenic density within the uterine cavity. The thickness of the uterine wall and the fundus could be clearly identified in a normal insertion. In the presence of uterine perforation, the applicator was seen traversing the myometrium necessitating alteration of the treatment plan. PMID- 2203721 TI - Leucine kinetics in endurance-trained humans. AB - This study compared whole-body leucine kinetics in endurance-trained (TRN) and sedentary (SED) control subjects. Eleven men and women (6 TRN, 5 SED) underwent a 6-h primed, constant-rate infusion of L-[1-13C]leucine. Leucine turnover and oxidation were measured using tracer dilution and by measuring 13C enrichment of expired CO2 combined with respiratory calorimetry. Whole-body leucine turnover was greater in the TRN subjects (P less than 0.004; TRN 98.3 +/- 5.0, SED 75.3 +/ 4.2 mumol.kg-1.h-1; mean +/- SE), but there was no difference between groups in leucine oxidation (TRN 13.1 +/- 0.97, SED 11.5 +/- 0.48 mumol.kg-1.h-1). Thus more leucine turnover was available for nonoxidative utilization. In addition, the TRN subjects had higher resting energy expenditures compared with the SED group, and when all subjects were included in the analysis, there was a significant correlation between energy expenditure and protein turnover (n = 11, R = 0.61, P = 0.05). Therefore the heightened resting energy expenditure in the TRN subjects may be accounted for by an increased whole-body protein turnover. These results suggest that endurance training results in increased leucine and/or protein turnover, which may contribute to the increased resting energy expenditure observed in these subjects. PMID- 2203722 TI - Effect of CPAP on respiratory effort and dyspnea during exercise in severe COPD. AB - Recent work has demonstrated the ability of continuous positive airway pressure (CPAP) to relieve dyspnea during exercise in patients with severe chronic obstructive pulmonary disease (COPD). The present study examined the effects of CPAP (7.5-10 cmH2O) on the pattern of respiratory muscle activation and its relationship to dyspnea during constant work load submaximal bicycle exercise [20 +/- 4.8 (SE) W] in eight COPD patients (forced expiratory volume in 1 s = 25 +/- 3% predicted). Tidal volume, respiratory rate, minute ventilation, and end expiratory lung volume increased with exercise as expected. There was no change in breathing pattern, end-expiratory lung volume, or pulmonary compliance and resistance with the addition of CPAP. CPAP reduced inspiratory muscle effort, as indicated by the pressure-time integral of transdiaphragmatic (integral of Pdi.dt) and esophageal pressure (integral of Pes.dt, P less than 0.01 and P less than 0.05, respectively). In contrast, the pressure-time integral of gastric pressure (integral of Pga.dt), used as an index of abdominal muscle recruitment during expiration, increased (P less than 0.01). Dyspnea improved with CPAP in five of the eight patients. The amelioration of dyspnea was directly related to reductions in integral of Pes.dt (P less than 0.001) but inversely related to increases in integral of Pga.dt (P less than 0.01). In conclusion, CPAP reduces inspiratory muscle effort during exercise in COPD patients. However, the expected improvement in dyspnea is not seen in all patients and may be explained by more marked increases in expiratory muscle effort in some individuals. PMID- 2203723 TI - Functional and morphological changes in the eccrine sweat gland with heat acclimation. AB - Three adult male patas monkeys (11-15 kg) were heat acclimated by continuous exposure to an ambient temperature of 33 +/- 1 degree C at 13% relative humidity for 9 mo. During the last month, they were also exposed to 45 degrees C at 10% relative humidity for 4 h/day and 5 days/wk. Before and after 3 wk of acclimation, the animals were given a heat-tolerance test in which rectal (Tre) and mean skin (Tsk) temperatures, heart rate, and sweat rate (msw) were monitored during a 90-min exposure to 45 degrees C heat with 24% relative humidity under lenperone (1.0-1.4 mg/kg im) tranquilization. Maximal in vivo msw was also determined in response to subcutaneous injections (1 and 10% solutions) of methacholine (MCh). Before and after 9 wk and 9 mo of acclimation, sweat glands were dissected from biopsy specimens of the lateral calf, cannulated, and stimulated in vitro with MCh. Morphological measurements of isolated tubules were compared with maximal secretory rates produced by MCh stimulation. Three weeks of acclimation 1) reduced Tre and Tsk and increased msw during the heat tolerance test and 2) significantly increased maximal msw in response to MCh stimulation. Acclimation also increased (P less than 0.05) sweat gland size, as measured by tubular length and tubular volume. Maximal in vitro msw produced by MCh stimulation and msw per unit length of secretory coil also increased significantly. We conclude that heat acclimation increases the size of eccrine sweat glands and that these larger glands produce more sweat. They are also more efficient because they produce more sweat per unit length of secretory coil. PMID- 2203724 TI - Venous air embolism in swine: transport of gas bubbles through the pulmonary circulation. AB - The assumption that the lung is an effective filter for gas bubbles is of importance for certain occupations (e.g., divers, astronauts) as well as in the accomplishment of several medical procedures. The filtering capacity was tested in pigs by use of continuous air infusion into the right ventricle and a transesophageal echocardiographic transducer for detection of air in the left atrium. Twenty pigs, anesthetized with pentobarbital sodium and mechanically ventilated, were divided into groups that received air at infusion rates of 0.05 (group 1a, n = 7), 0.10 (group 2, n = 6), and 0.20 (group 3, n = 5) ml.kg-1.min 1. Two pigs served as controls. The breakthrough incidence was 0, 67, and 100%, respectively. Group 1a received a second infusion of 0.10 ml.kg-1.min-1 (group 1b, n = 7), and spillover of bubbles occurred in only 14% of these pigs. Infusion of gas caused a maximum increase in mean pulmonary arterial pressure (PAP) of 129 +/- 9% to 39.2 +/- 1.3 (SE) mmHg, with no significant difference between the groups. Breakthrough was observed only in animals with a dramatic reduction in mean arterial pressure and a PAP that returned to almost-normal values at spillover time. Our results suggest that the threshold value for breakthrough of air bubbles in pigs is reduced compared with that in dogs. The hemodynamic consequences at a given infusion rate are, however, greatly enhanced. PMID- 2203726 TI - Effect of an acute bout of exercise on glucose disposal in human obesity. AB - The effect of acute exercise on insulin action has been studied in six obese (150 250% ideal body weight) non-insulin-dependent diabetics (OD), seven obese normoglycemics (ON), and six lean healthy controls (LC). Using a three-stage euglycemic clamp, the metabolic clearance rate (MCR) of glucose under increasing insulin concentrations was measured. The insulin dose-response curve was assessed on two separate occasions: 1) a base-line test and 2) 1 h after aerobic treadmill exercise at a steady-state heart rate of 150-160 beats/min. In the base-line test, under all insulin levels, glucose MCR was significantly lower in obese compared with lean individuals (P less than 0.01). Exercise increased glucose MCR at the highest hormonal concentrations applied to 124 and 134% of base line in OD and in ON, respectively (P less than 0.05); the insulin concentration required for one-half of the maximal clearance rate of glucose achieved in this study decreased from 200 to 130 and from 160 to 95 microU/ml in OD and ON, respectively (P less than 0.05). The changes in these parameters were insignificant in LC. It is suggested that acute exercise affected the insulin dose-response curve in OD and in ON but not in LC; although enhanced by exercise, glucose MCR remained significantly lower in both obese groups compared with control subjects. We concluded that insulin resistance, which accompanies extreme obesity, could be markedly decreased but not completely reversed by one bout of exercise. PMID- 2203725 TI - Diminished arginine-stimulated insulin secretion in trained men. AB - Glucose-stimulated insulin secretion is depressed by training. To further elucidate the beta-cell adaptation to training, a nonglucose secretagogue was applied. Arginine was infused for 90 min to seven trained and seven untrained young men. Arginine and glucose concentrations increased identically in the groups. The insulin response was biphasic and waned despite increasing arginine concentrations. Both these phases as well as C-peptide responses were reduced in trained subjects, whereas proinsulin responses were similar in the groups. Identical increases were found in glucagon, growth hormone, catecholamines, and production and disappearance of glucose; identical decreases were found in free fatty acids, glycerol, and beta-hydroxybutyrate. In conclusion, in men training diminishes both arginine- and glucose-stimulated insulin secretion, indicating a profound beta-cell adaptation. Being enhanced, the effects of insulin on both production and disposal of glucose are changed in the opposite direction to beta cell secretion by training. The responses of glucagon- and growth hormone secreting cells to arginine do not change with training. PMID- 2203727 TI - Locations of genes in the 52-minute region on the physical map of Escherichia coli K-12. PMID- 2203728 TI - Locations of the speA, speB, speC, and metK genes on the physical map of Escherichia coli. PMID- 2203729 TI - Monitoring of naphthalene catabolism by bioluminescence with nah-lux transcriptional fusions. AB - We have demonstrated the efficacy of a light-generating genetic construction in describing the induction of a nah operon for the catabolism of naphthalene. A fragment from plasmid NAH7, which contains the promoter for the upper pathway of degradation, was transcriptionally fused to the lux genes of Vibrio fischeri. A Pseudomonas strain containing this construction is inducible to high levels of light production in the presence of a suitable substrate and the nahR regulatory gene product. This system was used to examine catabolic activity in a unique manner under a variety of growth conditions. Induction of bioluminescence was demonstrated to coincide with naphthalene degradation in all cases through the use of mineralization assays. A significant delay in bioluminescence and biodegradation was observed when naphthalene was added to batch cultures that were growing exponentially. These results suggest that the metabolism of naphthalene by this Pseudomonas strain is optimal when the growth rate of the culture is slow and is greatly reduced during exponential growth. PMID- 2203730 TI - Adaptation of Salmonella typhimurium mutants containing uncoupled enzyme IIGlc to glucose-limited conditions. AB - Uncoupled enzyme IIGlc of the phosphoenolpyruvate (PEP):glucose phosphotransferase system (PTS) in Salmonella typhimurium is able to catalyze glucose transport in the absence of PEP-dependent phosphorylation. As a result of the ptsG mutation, the apparent Km of the system for glucose transport is increased about 1,000-fold (approximately 18 mM) compared with wild-type PTS mediated glucose transport. An S. typhimurium mutant containing uncoupled enzyme IIGlc as the sole system for glucose uptake was grown in glucose-limited chemostat cultures. Selective pressure during growth in the chemostat resulted in adaptation to the glucose-limiting conditions in two different ways. At first, mutations appeared that led to a decrease in Km value of uncoupled enzyme IIGlc. These results suggested that uncoupled enzyme IIGlc had significant control on the growth rate under glucose-limiting conditions. More efficient glucose uptake enabled a mutant to outgrow its parent and caused a decrease in the steady-state glucose concentration in the chemostat. At very low glucose concentrations (10 microM), mutants arose that contained a constitutively synthesized methyl-beta galactoside permease. Apparently, further changes in the uncoupled enzyme IIGlc did not lead to a substantial increase in growth rate at very low glucose concentrations. PMID- 2203731 TI - A cloned avirulence gene from Pseudomonas solanacearum determines incompatibility on Nicotiana tabacum at the host species level. AB - A locus in Pseudomonas solanacearum AW1 responsible for the hypersensitive response (HR) on tobacco was cloned by complementation in the tobacco-pathogenic strain P. solanacearum NC252. The NC252 HR+ transconjugants lost pathogenicity on tobacco, indicating that the cloned locus could restrict the host range of NC252. Restriction enzyme mapping, transposon mutagenesis, and subcloning showed that, at most, 2.0 kilobases of the cloned DNA was required for NC252 transconjugants to elicit HR on tobacco. Site-directed insertional mutagenesis of the wild-type locus in strain AW1 to create AW1-31 eliminated HR activity on tobacco. However, AW1-31 retained pathogenicity on tomato and eggplant, confirming that this locus contains an avirulence gene, designated avrA. In contrast to the wild type, AW1 31 multiplied to almost the same extent as NC252 after infiltration into tobacco leaves. Nevertheless, AW1-31 did not wilt tobacco when stem inoculated, suggesting that additional factors condition host range. AW1 was HR+ on 27 N. tabacum cultivars, whereas AW1-31 was always HR-, strongly suggesting that avrA is specific at the host species level. PMID- 2203732 TI - Interaction of integration host factor from Escherichia coli with the integration region of the Haemophilus influenzae bacteriophage HP1. AB - The specific DNA-binding protein integration host factor (IHF) of Escherichia coli stimulates the site-specific recombination reaction between the attP site of bacteriophage HP1 and the attB site of its host, Haemophilus influenzae, in vitro and also appears to regulate the expression of HP1 integrase. IHF interacts specifically with DNA segments containing the att sites and the integrase regulatory region, as judged by IHF-dependent retardation of relevant DNA fragments during gel electrophoresis. The locations of the protein-binding sites were identified by DNase I protection experiments. Three sites in the HP1 attP region bound IHF, two binding sites were present in the vicinity of the attB region, and one region containing three partially overlapping sites was present in the HP1 integrase regulatory segment. The binding sites defined in these experiments all contained sequences which matched the consensus IHF binding sequences first identified in the lambda attP region. An activity which stimulated the HP1 site-specific integration reaction was found in extracts of H. influenzae, suggesting that an IHF-like protein is present in this organism. PMID- 2203733 TI - Cloning and nucleotide sequences of the Bacillus stearothermophilus neutral protease gene and its transcriptional activator gene. AB - Both the neutral protease gene (nprS) and its transcriptional activator gene (nprA) from Bacillus stearothermophilus TELNE were cloned in Bacillus subtilis by using pTB53 as a vector plasmid. The presence of the nprA gene enhanced protease synthesis by about fivefold. The nucleotide sequences of nprS and its flanking regions were determined. nprS was composed of 1,653 base pairs and 551 amino acid residues. A Shine-Dalgarno (SD) sequence was found 9 bases upstream from the translation start site (ATG). The deduced amino acid sequence was very similar to that of another thermostable neutral protease gene, nprM (M. Kubo and T. Imanaka, J. Gen. Microbiol. 134:1883-1892, 1988). the amino acid sequence of the extracellular neutral protease NprS was completely identical to that of NprM. By deletion analysis and substitution of the original promoter with a foreign promoter, it was found that the nprA gene existed upstream of nprS. It was also found that a possible target region (palindromic sequence) of the gene product of nprA existed near the promoter sequence of nprS. The nucleotide sequences of nprA and its flanking regions were determined. The DNA sequence revealed only one large open reading frame, composed of 1,218 base pairs (406 amino acids; molecular weight, 49,097). The SD sequence was found 4 bases upstream from the translation start site (GTG). A possible promoter sequence (TTGAAG for the -35 region and AATTTT for the -10 region) was also found about 20 bases upstream of the SD sequence. The nprA gene was separated from nprS by a typical terminator sequence. By constructing an in-frame fusion between the lacZ gene and the 5' region of the nprA gene, it was demonstrated that the coding region of nprA was indeed translated in vivo. Three palindromic sequences, which were highly homologous with a possible target region by NprA, were also found in the 5' region of the nprA gene. This suggests that eh expression of nprA is autoregulated. From the time course of the production of NprA-LacZ fusion protein, it was indicated that nprA was expressed in late log phase, whereas nprS was expressed in the stationary phase. The NprA protein had consensus regions homologous to the DNA recognition domains of DNA-binding proteins but showed no sequence homology with any other regulatory proteins for protease production. It is inferred that NprA protein binds to the upstream region of nprS promoter and activates transcription of nprS. A new regulatory mechanism by the nprA-nprS genes is discussed. PMID- 2203734 TI - Electrochemical potential releases a membrane-bound secretion intermediate of maltose-binding protein in Escherichia coli. AB - A secretionary intermediate of the Escherichia coli maltose-binding protein accumulated in the inner membrane when the membrane electrochemical potential was reduced and the cytosolic ATP concentration was normal. The intermediate was mature in size, but maintained a conformation similar to the cytosolic precursor form, and not the mature periplasmic protein, as measured by differences in susceptibility to proteinase K in vitro. The intermediate was located on the periplasmic side of the inner membrane. Restoration of the membrane electrochemical potential resulted in the movement of the intermediate from the inner membrane to the periplasm. In other experiments in which the ATP concentration was reduced by 96% and the electrochemical potential remained normal, no intermediate accumulated. Thus, the final step in the export of maltose-binding protein requires the electrochemical potential of the inner membrane and does not require ATP. PMID- 2203735 TI - Genetic and sequence organization of the mcrBC locus of Escherichia coli K-12. AB - The mcrB (rglB) locus of Escherichia coli K-12 mediates sequence-specific restriction of cytosine-modified DNA. Genetic and sequence analysis shows that the locus actually comprises two genes, mcrB and mcrC. We show here that in vivo, McrC modifies the specificity of McrB restriction by expanding the range of modified sequences restricted. That is, the sequences sensitive to McrB(+) dependent restriction can be divided into two sets: some modified sequences containing 5-methylcytosine are restricted by McrB+ cells even when McrC-, but most such sequences are restricted in vivo only by McrB+ McrC+ cells. The sequences restricted only by McrB+C+ include T-even bacteriophage containing 5 hydroxymethylcytosine (restriction of this phage is the RglB+ phenotype), some sequences containing N4-methylcytosine, and some sequences containing 5 methylcytosine. The sequence codes for two polypeptides of 54 (McrB) and 42 (McrC) kilodaltons, whereas in vitro translation yields four products, of approximately 29 and approximately 49 (McrB) and of approximately 38 and approximately 40 (McrC) kilodaltons. The McrB polypeptide sequence contains a potential GTP-binding motif, so this protein presumably binds the nucleotide cofactor. The deduced McrC polypeptide is somewhat basic and may bind to DNA, consistent with its genetic activity as a modulator of the specificity of McrB. At the nucleotide sequence level, the G+C content of mcrBC is very low for E. coli, suggesting that the genes may have been acquired recently during the evolution of the species. PMID- 2203737 TI - Structural characterization of the Salmonella typhimurium LT2 umu operon. AB - The umuDC operon of Escherichia coli encodes functions required for mutagenesis induced by radiation and a wide variety of chemicals. The closely related organism Salmonella typhimurium is markedly less mutable than E. coli, but a umu homolog has recently been identified and cloned from the LT2 subline. In this study the nucleotide sequence and structure of the S. typhimurium LT2 umu operon have been determined and its gene products have been identified so that the molecular basis of umu activity might be understood more fully. S. typhimurium LT2 umu consists of a smaller 417-base-pair (bp) umuD gene ending 2 bp upstream of a larger 1,266-bp umuC gene. The only apparent structural difference between the two operons is the lack of gene overlap. An SOS box identical to that found in E. coli is present in the promoter region upstream of umuD. The calculated molecular masses of the umuD and umuC gene products were 15.3 and 47.8 kilodaltons, respectively, which agree with figures determined by transpositional disruption and maxicell analysis. The S. typhimurium and E. coli umuD sequences were 68% homologous and encoded products with 71% amino acid identity; the umuC sequences were 71% homologous and encoded products with 83% amino acid identity. Furthermore, the potential UmuD cleavage site and associated catalytic sites could be identified. Thus the very different mutagenic responses of S. typhimurium LT2 and E. coli cannot be accounted for by gross differences in operon structure or gene products. Rather, the ability of the cloned S. typhimurium umuD gene to give stronger complementation of E. coli umuD77 mutants in the absence of a functional umuC gene suggests that Salmonella UmuC protein normally constrains UmuD protein activity. PMID- 2203736 TI - Isolation and characterization of a beta-lactamase-inhibitory protein from Streptomyces clavuligerus and cloning and analysis of the corresponding gene. AB - Culture filtrates of Streptomyces clavuligerus contain a proteinaceous beta lactamase inhibitor (BLIP) in addition to a variety of beta-lactam compounds. BLIP was first detected by its ability to inhibit Bactopenase, a penicillinase derived from Bacillus cereus, but it has also been shown to inhibit the plasmid pUC- and chromosomally mediated beta-lactamases of Escherichia coli. BLIP showed no inhibitory effect against Enterobacter cloacae beta-lactamase, and it also showed no activity against an alternative source of B. cereus penicillinase. BLIP was purified to homogeneity, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis gave a size estimate for BLIP of 16,900 to 18,000. The interaction between purified BLIP and the E. coli(pUC) beta-lactamase was investigated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and determined to be noncovalent, with an estimated 1:1 molar stoichiometry. The BLIP gene was isolated on a 13.5-kilobase fragment of S. clavuligerus chromosomal DNA which did not overlap a 40-kilobase region of DNA known to contain genes for beta lactam antibiotic biosynthesis. The gene encoded a mature protein with a deduced amino acid sequence of 165 residues (calculated molecular weight of 17,523) and also encoded a 36-amino-acid signal sequence. No significant sequence similarity to BLIP was found by pairwise comparisons using various protein and nucleotide sequence data banks or by hybridization experiments, and no BLIP activity was detected in the culture supernatants of other Streptomyces spp. PMID- 2203738 TI - Rhodobacter capsulatus genes involved in early steps of the bacteriochlorophyll biosynthetic pathway. AB - Three open reading frames in the Rhodobacter capsulatus photosynthesis gene cluster, designated F0, F108, and F1025, were disrupted by site-directed mutagenesis. Mutants bearing insertions in these reading frames were defective in converting protoporphyrin IX to magnesium-protoporphyrin monomethyl ester, protochlorophyllide to chlorophyllide a, and magnesium-protoporphyrin monomethyl ester to protochlorophyllide, respectively. These results demonstrate that the genes examined most likely encode enzyme subunits that catalyze steps common to plant and bacterial tetrapyrrole photopigment biosynthetic pathways. The open reading frames were found to be part of a large 11-kilobase operon that encodes numerous genes involved in early steps of the bacteriochlorophyll a biosynthetic pathway. PMID- 2203739 TI - Interaction between heat shock protein DnaK and recombinant staphylococcal protein A. AB - When a protein derived from the immunoglobulin G (IgG)-binding domains of staphylococcal protein A was expressed in Escherichia coli and recovered from cell extract by IgG affinity chromatography, the 69-kilodalton heat shock protein DnaK was found to be copurified. DnaK could be selectively eluted from the IgG column by ATP or by lowering the pH to 4.7. Protein A could subsequently be eluted by lowering the pH to 3.2. Thus, this procedure allows a one-step purification of both DnaK and protein A from cell extract. In vitro experiments with pure DnaK and protein A revealed that DnaK did not interfere with the IgG binding properties of protein A but associated with its unfolded C-terminal in a salt-resistant manner. In addition, a specific interaction between DnaK and denaturated casein was found. PMID- 2203740 TI - Effect of growth temperature on folding of carbamoylphosphate synthetases of Salmonella typhimurium and a cold-sensitive derivative. AB - The properties of homogeneous preparations of carbamoylphosphate synthetase (CPSase) from wild-type Salmonella typhimurium and a cold-sensitive derivative grown at different growth temperatures were examined. For the cold-sensitive mutant, the affinity for glutamine of the form of CPSase synthesized at 20 degrees C was lower than that of the form of the enzyme synthesized at 37 degrees C, regardless of the assay temperature. Thus, the cold sensitivity of the mutant reflects an effect of temperature on the synthesis of the enzyme rather than the activity of the folded enzyme. The two forms also differed in sensitivities to polyclonal antibodies as well as denaturational enthalpies. The combined results support the hypothesis that carAB mutations conferring cold sensitivity identify amino acid residues that are critical in the folding of CPSase. Quite unexpectedly, certain kinetic properties of cloned parent CPSase were also dependent on the growth temperature, although to a much lesser extent than those of the cold-sensitive mutant. The specific activity of wild-type CPSase synthesized at 15 degrees C was 60% of that synthesized at 37 degrees C. Further, CPSase synthesized at 15 degrees C was less thermostable than the enzyme synthesized at 37 degrees C; the difference in stability (delta G) is estimated to be 4,500 cal mol-1. Thus, variation of temperature within the physiological range for growth influences the folding and consequently the properties of CPSase from wild-type S. typhimurium. PMID- 2203741 TI - The native form of FtsA, a septal protein of Escherichia coli, is located in the cytoplasmic membrane. AB - Antisera able to recognize FtsA, one of the septal proteins of Escherichia coli, have been obtained and used to show that native FtsA, when expressed at levels ranging from physiological to induced from lambda pR, is located in the inner membrane. Experiments of trypsin accessibility to FtsA in membranes, spheroplasts, and vesicles indicated that FtsA is located such that it faces the cytoplasm. This location is consistent with current knowledge about the participation of FtsA in a molecular complex active in cell division called septator. PMID- 2203742 TI - Nutrient-dependent methylation of a membrane-associated protein of Escherichia coli. AB - Starvation of a mid-log-phase culture of Escherichia coli B/r for nitrogen, phosphate, or carbon resulted in methylation of a membrane-associated protein of about 43,000 daltons (P-43) in the presence of chloramphenicol and [methyl 3H]methionine. The in vivo methylation reaction occurred with a doubling time of 2 to 5 min and was followed by a slower demethylation process. Addition of the missing nutrient to a starving culture immediately prevented further methylation of P-43. P-43 methylation is not related to the methylated chemotaxis proteins because P-43 is methylated in response to a different spectrum of nutrients and because P-43 is methylated on lysine residues. The characteristics of P-43 are similar to those of a methylated protein previously described in Bacillus subtilis and B. licheniformis (R. W. Bernlohr, A. L. Saha, C. C. Young, B. R. Toth, and K. J. Golden, J. Bacteriol. 170:4113-4118, 1988; K. J. Golden and R. W. Bernlohr, Mol. Gen. Genet. 220:1-7, 1989) and are consistent with the proposal that methylation of this protein functions in nutrient sensing. PMID- 2203743 TI - Complementation analysis of Agrobacterium tumefaciens Ti plasmid virB genes by use of a vir promoter expression vector: virB9, virB10, and virB11 are essential virulence genes. AB - The virB gene products of the Agrobacterium tumefaciens tumor-inducing (Ti) plasmid have been proposed to mediate T-DNA transport through the bacterial cell wall into plant cells. Previous genetic analysis of the approximately 9.5 kilobase-pair virB operon has been limited to transposon insertion mutagenesis. Due to the polarity of the transposon insertions, only the last gene in the operon, virB11, is known to provide an essential virulence function. We have now begun to assess the contribution of the other virB genes to virulence. First, several previously isolated Tn3-HoHo1 insertions in the 3' end of the virB operon were precisely mapped by nucleotide sequence analysis. Protein extracts from A. tumefaciens strains harboring these insertions on the Ti plasmid were subjected to immunostaining analysis with VirB4-, VirB10-, and VirB11-specific antisera to determine the effect of the insertion on virB gene expression. In this manner, avirulent mutants containing polar insertions in the virB9 and virB10 genes were identified. To carry out a complementation analysis with these virB mutants, expression vectors were constructed that allow cloned genes to be expressed from the virB promoter in A. tumefaciens. These plasmids were used to express combinations of the virB9, virB10, and virB11 genes in trans in the virB insertion mutants, thereby creating strains lacking only one of these three virB gene products. Virulence assays on Kalanchoe daigremontiana demonstrated that in addition to virB11, the virB9 and virB10 genes are required for tumorigenicity. PMID- 2203744 TI - Repellents for Escherichia coli operate neither by changing membrane fluidity nor by being sensed by periplasmic receptors during chemotaxis. AB - A long-standing question in bacterial chemotaxis is whether repellents are sensed by receptors or whether they change a general membrane property such as the membrane fluidity and this change, in turn, is sensed by the chemotaxis system. This study addressed this question. The effects of common repellents on the membrane fluidity of Escherichia coli were measured by the fluorescence polarization of the probe 1,6-diphenyl-1,3,5-hexatriene in liposomes made of lipids extracted from the bacteria and in membrane vesicles. Glycerol, indole, and L-leucine had no significant effect on the membrane fluidity. NiSO4 decreased the membrane fluidity but only at concentrations much higher than those which elicit a repellent response in intact bacteria. This indicated that these repellents are not sensed by modulating the membrane fluidity. Aliphatic alcohols, on the other hand, fluidized the membrane, but the concentrations that elicited a repellent response were not equally effective in fluidizing the membrane. The response of intact bacteria to alcohols was monitored in various chemotaxis mutants and found to be missing in mutants lacking all the four methyl accepting chemotaxis proteins (MCPs) or the cytoplasmic che gene products. The presence of any single MCP was sufficient for the expression of a repellent response. It is concluded (i) that the repellent response to aliphatic alcohols can be mediated by any MCP and (ii) that although an increase in membrane fluidity may take part in a repellent response, it is not the only mechanism by which aliphatic alcohols, or at least some of them, are effective as repellents. To determine whether any of the E. coli repellents are sensed by periplasmic receptors, the effects of repellents from various classes on periplasm-void cells were examined. The responses to all the repellents tested (sodium benzoate, indole, L-leucine, and NiSO4) were retained in these cells. In a control experiment, the response of the attractant maltose, whose receptor is periplasmic, was lost. This indicates that these repellents are not sensed by periplasmic receptors. In view of this finding and the involvement of the MCPs in repellent sensing, it is proposed that the MCPs themselves are low-affinity receptors for the repellents. PMID- 2203745 TI - Functional and evolutionary relatedness of genes for exopolysaccharide synthesis in Rhizobium meliloti and Rhizobium sp. strain NGR234. AB - Rhizobium meliloti SU47 and Rhizobium sp. strain NGR234 produce distinct exopolysaccharides that have some similarities in structure. R. meliloti has a narrow host range, whereas Rhizobium strain NGR234 has a very broad host range. In cross-species complementation and hybridization experiments, we found that several of the genes required for the production of the two polysaccharides were functionally interchangeable and similar in evolutionary origin. NGR234 exoC and exoY corresponded to R. meliloti exoB and exoF, respectively. NGR234 exoD was found to be an operon that included genes equivalent to exoM, exoA, and exoL in R. meliloti. Complementation of R. meliloti exoP, -N, and -G by NGR234 R'3222 indicated that additional equivalent genes remain to be found on the R-prime. We were not able to complement NGR234 exoB with R. meliloti DNA. In addition to functional and evolutionary equivalence of individual genes, the general organization of the exo regions was similar between the two species. It is likely that the same ancestral genes were used in the evolution of both exopolysaccharide biosynthetic pathways and probably of pathways in other species as well. PMID- 2203746 TI - Synthesis of Escherichia coli heat-stable enterotoxin STp as a pre-pro form and role of the pro sequence in secretion. AB - Escherichia coli heat-stable enterotoxin STp is presumed from its DNA sequence to be synthesized in vivo as a 72-amino-acid residue precursor that is cleaved to generate mature STp consisting of the 18 carboxy-terminal amino acid residues. There are two methionine residues in the inferred STp sequence in addition to the methionine residue at position 1. In order to confirm production of the STp 72 amino-acid residue precursor, we substituted the additional methionine residues by oligonucleotide-directed site-specific mutagenesis. Since these substitutions did not cause a significant change in STp production, it can be concluded that STp is normally synthesized as the 72-amino-acid residue precursor. The length of the STp precursor indicated the existence of a pro sequence between the signal peptide and the mature protein. In order to identify the pro sequence and determine its role in protein secretion, deletion and fusion proteins were made. A deletion mutant in which the gene fragment encoding amino acid residues 22 to 53 of STp was removed was made. STp activity was found in the culture supernatant of cells. Amino acid sequence analysis of the purified STp deletion mutant revealed that the pro sequence encompasses amino acid residues 20 to 54. A hybrid protein consisting of STp amino acids 1 to 53 fused in frame from residue 53 to nuclease A was not secreted into the culture supernatant. These results indicate that the pro sequence does not function to guide periplasmic protein into the extracellular milieu. PMID- 2203747 TI - Isolation of the replication and partitioning regions of the Salmonella typhimurium virulence plasmid and stabilization of heterologous replicons. AB - Although the virulence plasmid of Salmonella typhimurium has a copy number of one to two per chromosome, plasmid-free segregants are produced at a rate less than 10(-7) per cell per generation. Three regions appear to be involved in the maintenance of this virulence plasmid. The first two, repB and repC, are functional replicons hybridizing with IncFII and IncFI plasmids, respectively, neither exhibiting the segregational stability of the parent virulence plasmid. The third region, par, cloned as a 3.9-kilobase Sau3A fragment, is not a functional replicon but exhibits incompatibility with the virulence plasmid. Subsequent tests revealed the ability of this 3.9-kilobase par insert to increase the stability of pACYC184 in S. typhimurium from less than 34% to 99% plasmid containing cells after 50 generations. In addition, the par region increased the stability of oriC, R388, and repC replicons in both S. typhimurium and Escherichia coli hosts. The par region encodes 44,000- and 40,000-molecular weight proteins essential for the Par+ phenotype but not for the Inc+ phenotype. Although actual sequestering of plasmids within the cell was not demonstrated, all results indicate that the par region described is an actual partitioning locus, similar in organization to those described for plasmids F, P1, and NR1. PMID- 2203748 TI - Uracil-DNA glycosylase causes 5-bromodeoxyuridine photosensitization in Escherichia coli K-12. AB - An Escherichia coli uracil-DNA glycosylase-defective mutant (ung-1 thyA) was more resistant than its wild-type counterpart (ung+ thyA) to the killing effect of UV light when cultured in medium containing 5-bromouracil or 5-bromo-2'-deoxyuridine (BrdUrd). The phenotype of resistance to BrdUrd photosensitization and the uracil DNA glycosylase deficiency appeared to be 100% cotransduced by P1 phage. During growth with BrdUrd, both strains exhibited similar growth rates and 5-bromouracil incorporation into DNA. The resistant phenotype of the ung-1 mutant was observed primarily during the stationary phase. In cells carrying 5-bromouracil substituted DNA, mutations causing resistance to rifampin and valine were induced by UV irradiation at a higher frequency in the wild type than in the ung-1 mutant. This Ung-dependent UV mutagenesis required UmuC function. These results suggest that the action of the uracil-DNA glycosylase on UV-irradiated 5 bromouracil-substituted DNA produces lethal and mutagenic lesions. The BrdUrd photosensitization-resistant phenotype allowed us to develop a new, efficient method for enriching and screening ung mutants. PMID- 2203749 TI - Integration host factor is a negative effector of in vivo and in vitro expression of ompC in Escherichia coli. AB - Integration host factor (IHF) of Escherichia coli is a DNA-binding protein involved in gene expression and other cellular functions in E. coli and some of its bacteriophages and plasmids. We report here that IHF is a direct negative effector of the ompC operon of E. coli. IHF binds to ompC DNA and protects a region of 35 base pairs located upstream from the ompC promoters. The addition of IHF to a purified in vitro transcription system inhibited transcription from two of the three ompC promoters. In vivo experiments suggest that the in vitro results are physiologically relevant. IHF mutants show increased expression of OmpC. In addition, the OmpC- phenotype of certain strains is completely suppressed by a mutation in IHF. PMID- 2203750 TI - Reconstitution of an active lactose carrier in vivo by simultaneous synthesis of two complementary protein fragments. AB - Escherichia coli lactose permease mediates the proton-driven translocation of galactosides across the cytoplasmic membrane. To define regions important for membrane insertion as well as for biological function, we constructed plasmids encoding different portions of the lactose carrier. Among several lacY deletions, two were obtained that encoded mutant proteins with complementary amino acid sequences. The truncated polypeptide Y71/1 (amino acid residues 1 to 71) comprises the first two alpha-helices predicted for the intact protein, and polypeptide delta Y4-69 carries an internal deletion of this region. Regulated coexpression of these lacY-DNA segments governed by separate but identical lacOP control regions resulted in functional complementation with the following characteristics. (i) Simultaneous synthesis of both incomplete proteins restored transport activity in transport-negative cells, measured as accumulation of [14C]lactose. (ii) Under complementing conditions, but not in the absence of the smaller N-terminal protein, specific radiolabeling of the larger polypeptide by N ethylmaleimide was prevented by substrate. (iii) The presence of the complementing N-terminal polypeptide was also required for the detection of the larger C-terminal protein by antibodies directed against the C terminus of lactose permease, indicating a stabilizing effect contributed by the smaller N terminal fragment. Thus, coexpression of lacY mutant genes encoding two nonoverlapping portions of the lactose carrier resulted in reconstitution of a two-subunit protein in the cytoplasmic membrane exhibiting biological properties of intact lactose permease. PMID- 2203751 TI - A locus affecting nucleoid segregation in Salmonella typhimurium. AB - Thirteen temperature-sensitive lethal mutations of Salmonella typhimurium map near metC at 65 min and form the clmF (conditional lethal mutation) locus. The mutations in this region were ordered by three-point transduction crosses. After a shift to the nonpermissive temperature, many of these clmF mutants failed to complete the segregation of nucleoids into daughter cells; daughter nucleoids appeared incompletely separated and asymmetrically positioned within cells. Some clmF mutants showed instability of F' episomes at permissive growth temperatures yet showed no detectable defect with smaller multicopy plasmids such as pSC101 or pBR322. In addition, many of the clmF mutants rapidly lost viability yet continued DNA replication at the nonpermissive temperature. These results suggest that the clmF locus encodes at least one indispensable gene product that is required for faithful partitioning of the bacterial nucleoid and F-plasmid replicons. PMID- 2203752 TI - Physiological consequences of the complete loss of phosphoryl-transfer proteins HPr and FPr of the phosphoenolpyruvate:sugar phosphotransferase system and analysis of fructose (fru) operon expression in Salmonella typhimurium. AB - Mutants of Salmonella typhimurium defective in the proteins of the fructose operon [fruB(MH)KA], the fructose repressor (fruR), the energy-coupling enzymes of the phosphoenolpyruvate:sugar phosphotransferase system (PTS) (ptsH and ptsI), and the proteins of cyclic AMP action (cya and crp) were analyzed for their effects on cellular physiological processes and expression of the fructose operon. The fru operon consists of three structural genes: fruB(MH), which encodes the enzyme IIIFru-modulator-FPr tridomain fusion protein of the PTS; fruK, which encodes fructose-1-phosphate kinase; and fruA, which encodes enzyme IIFru of the PTS. Among the mutants analyzed were Tn10 insertion mutants and lacZ transcriptional fusion mutants. It was found that whereas a fruR::Tn10 insertion mutant, several fruB(MH)::Mu dJ and fruK::Mu dJ fusion mutants, and several ptsHI deletion mutants expressed the fru operon and beta-galactosidase at high constitutive levels, ptsH point mutants and fruA::Mu dJ fusion mutants retained inducibility. Inclusion of the wild-type fru operon in trans did not restore fructose-inducible beta-galactosidase expression in the fru::Mu dJ fusion mutants. cya and crp mutants exhibited reduced basal activities of all fru regulon enzymes, but inducibility was not impaired. Surprisingly, fruB::Mu dJ crp or cya double mutants showed over 10-fold inducibility of the depressed beta galactosidase activity upon addition of fructose, even though this activity in the fruB::Mu dJ fusion mutants that contained the wild-type cya and crp alleles was only slightly inducible. By contrast, beta-galactosidase activity in a fruK::Mu dJ fusion mutant, which was similarly depressed by introduction of a crp or cya mutation, remained constitutive. Other experiments indicated that sugar uptake via the PTS can utilize either FPr-P or HPr-P as the phosphoryl donor, but that FPr is preferred for fructose uptake whereas HPr is preferred for uptake of the other sugars. Double mutants lacking both proteins were negative for the utilization of all sugar substrates of the PTS, were negative for the utilization of several gluconeogenic carbon sources, exhibited greatly reduced adenylate cyclase activity, and were largely nonmotile. These phenotypic properties are more extreme than those observed for tight ptsH and ptsI mutants, including mutants deleted for these genes. A biochemical explanation for this fact is proposed. PMID- 2203753 TI - Nucleotide sequence of the gene encoding the repressor for the histidine utilization genes of Pseudomonas putida. AB - The hutC gene of Pseudomonas putida encodes a repressor which, in combination with the inducer urocanate, regulates expression of the five structural genes necessary for conversion of histidine to glutamate, ammonia, and formate. The nucleotide sequence of the hutC region was determined and found to contain two open reading frames which overlapped by one nucleotide. The first open reading frame (ORF1) appeared to encode a 27,648-dalton protein of 248 amino acids whose sequence strongly resembled that of the hut repressor of Klebsiella aerogenes (A. Schwacha and R. A. Bender, J. Bacteriol. 172:5477-5481, 1990) and contained a helix-turn-helix motif that could be involved in operator binding. The gene was preceded by a sequence which was nearly identical to that of the operator site located upstream of hutU which controls transcription of the hutUHIG genes. The operator near hutC would presumably allow the hut repressor to regulate its own synthesis as well as the expression of the divergent hutF gene. A second open reading frame (ORF2) would encode a 21,155-dalton protein, but because this region could be deleted with only a slight effect on repressor activity, it is not likely to be involved in repressor function or structure. PMID- 2203754 TI - Nucleotide sequence of the gene encoding the repressor for the histidine utilization genes of Klebsiella aerogenes. AB - The hutC gene of Klebsiella aerogenes encodes a repressor that regulates expression of the histidine utilization (hut) operons. The DNA sequence of a region known to contain hutC was determined and shown to contain two long rightward-reading open reading frames (ORFs). One of these ORFs was identified as the 3' portion of the hutG gene. The other ORF was the hutC gene. The repressor predicted from the hutC sequence contained a helix-turn-helix motif strongly similar to that seen in other DNA-binding proteins, such as lac repressor and the catabolite gene activator protein. This motif was located in the N-terminal portion of the protein, and this portion of the protein seemed to be sufficient to allow repression of the hutUH operon but insufficient to allow interaction with the inducer. The presence of a promoterlike sequence and a ribosome-binding site immediately upstream of the hutC gene explained the earlier observation that hutC can be transcribed independently of the other hut operon genes. The predicted amino acid sequence of hut repressor strongly resembled that of the corresponding protein from Pseudomonas putida (S. L. Allison and A. T. Phillips, J. Bacteriol. 172:5470-5476, 1990). An unexpected, leftward-reading ORF extending from about the middle of hutC into the preceding (hutG) gene was also detected. The deduced amino acid sequence of this leftward ORF was quite distinct from that of an unexpected ORF of similar size found immediately downstream of the P. putida hutC gene. The nonstandard codon usage of this leftward ORF and the expression of repressor activity from plasmids with deletions in this region made it unlikely that this ORF was necessary for repressor activity. PMID- 2203755 TI - Subcellular localization of the Rhizobium leguminosarum nodI gene product. AB - By the use of antibodies raised against a fusion protein of lacZ'-nodI (produced in Escherichia coli) which specifically react with NodI protein, it was shown that in wild-type Rhizobium leguminosarum biovar viciae NodI protein (i) is recovered with the cytoplasmic membrane fraction and (ii) is translated as part of the nodABCIJ operon. In addition, it was found that the bacterial chromosomal background strongly influences the expression of several nod genes. PMID- 2203756 TI - The heat-stable toxin I gene from Escherichia coli 18D. AB - The heat-stable toxin I gene in the human Escherichia coli isolate 18D is the estA1 allele. The gene is not part of a composite transposon, but inspection of the flanking DNA sequences suggests that it was at one time part of a transposon. The hypothetical transposon originated from an event other than the occurrence that formed Tn1681. PMID- 2203757 TI - Oxygen regulation of L-1,2-propanediol oxidoreductase activity in Escherichia coli. AB - Regardless of the respiratory conditions of the culture, Escherichia coli synthesizes an active propanediol oxidoreductase. Under anaerobic conditions, the enzyme remained fully active and accomplished its physiological role, while under aerobic conditions, it was inactivated in a process that did not depend on protein synthesis or on the presence of a carbon source. PMID- 2203758 TI - Nucleoprotein structures initiating DNA replication, transcription, and site specific recombination. PMID- 2203759 TI - Polyisoprenylation of Ras in vitro by a farnesyl-protein transferase. AB - Farnesylation of Ras occurs in vivo on a Cys residue in the C-terminal sequence Cys-Val-Leu-Ser (termed a CAAX box). This modification is required for Ras membrane localization and cell transforming activity. Using [3H]farnesyl-PPi as precursor and Escherichia coli-expressed Ras, forms of Ras having the CAAX sequence were radiolabeled upon incubation with the cytosolic fraction of bovine brain. Forms of Ras having a deletion of the CAAX sequence or a Cys to Ser substitution in this sequence were not substrates. Radioactivity incorporated into Ras by bovine brain cytosol was released by treatment with iodomethane but not with methanolic KOH indicating a thioether linkage. High pressure liquid chromatography analysis of the cleavage products on a C-18 column showed a major peak of radioactivity that co-eluted with a farnesol standard. The enzyme responsible for Ras farnesylation in bovine brain was approximately 190 kDa as estimated by gel filtration and required a divalent cation for activity. Nonradioactive farnesyl-PPi, geranylgeranyl-PPi, and Ras peptides having the C terminal sequence -Cys-Val-Leu-Ser competed in the assay with IC50 values of 0.7, 1.4, and 1-3 microM, respectively. Farnesol and Ras peptides having the sequence Ser-Val-Leu-Ser were not inhibitory. These results identify a farnesyl-protein transferase activity that may be responsible for the polyisoprenylation of Ras in intact cells. PMID- 2203760 TI - Ligand-specific transactivation of gene expression by a derivative of the human glucocorticoid receptor expressed in yeast. AB - In this study we have reconstituted transactivation of gene expression by the human glucocorticoid receptor in the yeast, Saccharomyces cerevisiae. We have expressed the C-terminal half of the human glucocorticoid receptor (residues 415 777), the smallest derivative that can be expected to function as a ligand dependent activator of transcription, in yeast cells. The function of the expressed protein has been assayed using a reporter gene consisting of the beta galactosidase gene from Escherichia coli fused to the yeast iso-1-cytochrome c promoter with a glucocorticoid-responsive element from the rat tyrosine aminotransferase gene upstream. Transactivation of expression from the reporter gene by the expressed receptor is seen only in the presence of steroid hormones with glucocorticoid activity and occurs via specific interaction of receptor with the glucocorticoid-responsive element upstream of the reporter gene. This result is different from those obtained for the estrogen receptor in which a similar derivative was not functional in yeast. This suggests that the well documented conservation of structure and function between steroid receptors may not extend to the transactivation domains. Our results also suggest that the mechanism by which receptors are sequestered in an inactive, non-DNA binding state in the absence of ligand may be functionally conserved in yeast. In support of this we show evidence that the expressed receptor is associated with the yeast molecular weight 90,000 heat shock protein as seen in mammalian cells. PMID- 2203761 TI - Phosphorylation state and biological function of a mutant human insulin receptor Val996. AB - Chinese hamster ovary (CHO) cell transfectants that expressed human insulin receptors whose glycine 996 was substituted by valine were studied. Receptor processing and insulin binding were unaffected by this mutation; however, this mutant insulin receptor had little or no tyrosine kinase activity. Nevertheless, the Val996 mutant exhibited seryl and threonyl phosphorylation in both the basal and insulin-stimulated state in intact cells. This is in contrast to the Lys--- Ala1018 tyrosine kinase deficient mutant (Russell, D. S., Gherzi, R., Johnson, E. L., Chou, C-K., and Rosen, O. M. (1987) J. Biol. Chem. 262, 11833-11840). Cells expressing the normal human receptor were 10-fold more sensitive to insulin than the untransfected CHO cells with respect to phosphorylation of a cellular substrate (pp 185) on tyrosyl residues, glucose incorporation into glycogen, thymidine incorporation into DNA, and phosphorylation of ribosomal protein S6. Cells expressing the mutant receptor exhibited the same insulin sensitivity as the untransfected CHO cells. Insulin was rapidly internalized in cells expressing the normal human receptor and the number of receptors expressed on the cell surface was decreased in response to exposure to insulin. However, little insulin was internalized in cells expressing the mutant receptor, and the number of receptors on the cell surface was not significantly diminished in response to exposure to insulin. It is concluded that despite the occurrence of seryl and threonyl phosphorylations, post-receptor effects of insulin described above are not mediated by the tyrosine kinase-deficient receptor, Val996. PMID- 2203762 TI - Agonist-mediated Ca2+ release in permeabilized UMR-106-01 cells. Transport properties and generation of inositol 1,4,5-trisphosphate. AB - Permeabilized and intact UMR-106-01 cells attached to culture plates or coverslips were used to evaluate compartmentalized generation and the effective concentration of inositol 1,4,5-trisphosphate (In-1,4,5-P3) during agonist mediated Ca2+ release. In permeabilized cells, Ca2+ release had the following characteristics. In-1,4,5-P3 released approximately 65% of the Ca2+ incorporated into intracellular stores. Prostaglandin F2 alpha (PGF2 alpha), endothelin, or GTP(gamma S) alone released a small amount or no Ca2+. However, the agonists together with GTP(gamma S) were as effective as In-1,4,5-P3 in releasing Ca2+. Both agonist- and In-1,4,5-P3-mediated Ca2+ release required the presence of permeable ion. Agonists, like In-1,4,5-P3, stimulated 45Ca uptake from low Ca2+ medium devoid of permeable ions into Ca2(+)-loaded intracellular stores. The permeabilized cell system was then used to evaluate compartmentalized generation and action of In-1,4,5-P3 during agonist stimulation. Mass measurement shows that in intact resting cells In-1,4,5-P3 concentration was 1.4 microM and was reduced to 0.05 microM following permeabilization. Stimulation with agonists increases In 1,4,5-P3 concentration from 0.05 to 0.34 microM. Ca2+ release by this concentration of In-1,4,5-P3 evenly distributed in the cytosol can account for only part of the agonist-mediated Ca2+ release. However, the effects of saturating In-1,4,5-P3 concentration and agonists were blocked by the specific inhibitor heparin. Measurement of heparin dependency of In-1,4,5-P3-mediated Ca2+ release was used to calculate an affinity for In-1,4,5-P3 of 0.39 microM. Similar measurements with agonists show that In-1,4,5-P3 concentration at the site of Ca2+ release during agonist stimulation is 11.2 microM. Hence, the total increase in In-1,4,5-P3 is reflected in considerably higher localized concentrations. This is interpreted to suggest compartmentalized generation and action of In-1,4,5-P3 during agonist stimulation. PMID- 2203763 TI - The dissociation and degradation of internalized insulin occur in the endosomes of rat hepatoma cells. AB - We have studied the intracellular processing of insulin in the rat hepatoma cell line Fao. Fao cells internalized cohorts of surface-bound 125I-insulin or 125I insulin-like growth factor II within 3-5 min. Degraded 125I-insulin-like growth factor II did not appear in the medium until 20-30 min after uptake, consistent with a time course of lysosomal delivery. In contrast, internalized insulin was completely degraded within 7-10 min. The half-times for dissociation and degradation of internalized insulin were identical at 37 degrees C (3 min), suggesting that the two processes occurred in the same compartment. Subcellular fractionation of Fao cells showed that a pulse of internalized insulin was largely intact after 3 min and associated with a light membrane fraction devoid of lysosomal markers. After an additional 4 min, the amount of insulin in this compartment decreased by 40%, with an increase in degraded insulin in the cytosol; no transfer of intact insulin to lysosomes or the cytosol was detected. The relationship between insulin-receptor dissociation and insulin degradation was further studied with inhibitors of insulin processing. Monensin blocked both dissociation and degradation of internalized insulin, as did incubation of the cells at 20 degrees C, suggesting that both endosomal acidification and endosomal fusion were required for insulin processing. At 25 degrees C, dissociation (+ t 1/2 = 12.9 min) preceded degradation (+ t 1/2 = 15.8 min). Inhibitors of lysosomal proteases were without effect on the half-time for either process. In contrast, bacitracin, an inhibitor of insulin degradation, caused a 2-fold increase in the half-times for both dissociation and degradation. Thus, intracellular insulin dissociation and degradation are tightly coupled endosomal processes in Fao cells, and insulin degradation facilitates the dissociation of insulin from its receptor inside the cell. PMID- 2203764 TI - Preferential DNA repair of alkali-labile sites within the active insulin gene. AB - DNA damage and repair were studied in a DNA fragment containing the insulin gene after treatment of cells with methylnitrosourea. For these studies, two clonal isolates from the same rat insulinoma cell line which differ in that the insulin gene is transcribed in one (RINr 38) and is silent in the other (RINr B2) were utilized. Both the determination of immunologically reactive insulin released and the expression of insulin mRNA were used to verify that the gene was transcribed in the RINr 38 cells and not in the RINr B2 cells. Repair kinetics for the removal of alkali-labile sites were comparable across the entire genome in the RINr 38 and RINr B2 cells as determined using alkaline sucrose gradient sedimentation and a 32P end-labeling assay for the quantitation of N7 methylguanine. Quantitative DNA blot analysis was utilized to assess the formation and repair of alkali-labile sites within the restriction fragment containing the insulin gene. Alkali-labile sites appeared to be formed equally within the restriction fragment containing the insulin gene in both the RINr 38 and RINr B2 cells. However, at 24 h, 60% of the lesions were removed from the fragment in the RINr 38 cells, where the gene was transcribed, compared to the removal of only 20% in the RINr B2 cells, where the gene was silent. Thus, it appears that alkali-labile sites induced by exposure to methylnitrosourea are repaired more efficiently in the DNA fragment containing the insulin gene when it is actively transcribed. PMID- 2203765 TI - Effects of insulin secretagogues on protein kinase C-catalyzed phosphorylation of an endogenous substrate in isolated pancreatic islets. AB - The influence of the insulin secretagogues, carbachol and glucose, on protein kinase C activation in isolated pancreatic islets has been examined by determination of the phosphorylation state of an endogenous 80-kDa protein substrate of protein kinase C. The islet 80-kDa protein was identified as the myristoylated alanine-rich C kinase substrate previously described (Stumpo D. J., Graff, J. M., Albert, K. A., Greengard, P., and Blackshear, P. J. (1989) Proc. Natl. Acad. Sci. U. S. A. 86, 4012-4016) by immunoprecipitation studies. The muscarinic agonist, carbachol (500 microM), induced insulin secretion and a time dependent increase in the phosphorylation state of this protein in islets. This phosphorylation was maximal (220 +/- 24% of control) at 5 min and was suppressed by the protein kinase C inhibitor, staurosporine. Concentrations of glucose (28 mM) which induce maximal insulin secretion did not induce a statistically significant increase in 80-kDa phosphorylation. The combination of carbachol and a submaximally stimulatory concentration of glucose (10 mM), when added simultaneously, exerted a marked synergistic effect on insulin secretion and a synergistic effect on the phosphorylation of the 80-kDa protein kinase C substrate. These data suggest that the activation of protein kinase C may play an important role in carbachol-induced insulin secretion and in the potentiation by carbachol of insulin secretion induced by glucose. However, the activation of protein kinase C does not appear to be a primary determinant of insulin secretion induced by glucose alone. PMID- 2203766 TI - Stimulus-response coupling in insulin-secreting HIT cells. Effects of secretagogues on cytosolic Ca2+, diacylglycerol, and protein kinase C activity. AB - The hamster islet B cell line HIT retains the ability to secret insulin in response to glucose and several receptor agonists. We used HIT cells to study the initial signaling events in glucose or receptor agonist-stimulated insulin secretion. Glucose stimulated insulin release from HIT cells in a dose-dependent manner with a half-maximal effect seen already at 1 mM. Insulin release was also stimulated by carbachol in a glucose-dependent manner. Glucose depolarized the HIT cell membrane potential as assessed with the fluorescent probe bisoxonol and raised intracellular Ca2+ as revealed by fura-2 measurements. Using a Mn2+ fura-2 quenching technique, we could show that the rise in intracellular Ca2+ was due to Ca2+ influx following opening of voltage-gated Ca2+ channels. Glucose is thought to increase the diacylglycerol (DAG) content of insulin-secreting cells. However, although HIT cells respond to glucose in terms of insulin secretion, membrane depolarization, and Ca2+ rise, the hexose was unable to increase the proportion of protein kinase C activity associated with membranes. In contrast, the membrane associated protein kinase C activity increased in HIT cells exposed to the two receptor agonists carbachol and bombesin. Bombesin was shown to generate DAG with the expected fatty acid composition of activators of phospholipase C. Glucose, in contrast, only caused minor increases in DAG containing myristic and palmitic acid without affecting total DAG mass. The failure to detect stimulation of protein kinase C by glucose could be due to both the limited amount and to the different fatty acid composition of the metabolically generated DAG. The latter was in part supported by experiments performed on protein kinase C partially purified from HIT cells. Indeed, 1,2-dipalmitoylglycerol, presumed to be the main DAG species generated by glucose, was only one-third as active as 1,2 dioleoylglycerol and 1-stearoyl-2-arachidonylglycerol in stimulating the isolated enzyme at physiological Ca2+ concentration. It is therefore unlikely that DAG and protein kinase C play a major role in glucose-stimulated insulin secretion. PMID- 2203767 TI - Ligand-induced isomerizations of Escherichia coli ornithine transcarbamoylase. An ultraviolet difference analysis. AB - Ligand-induced ultraviolet difference spectra have been determined for Escherichia coli ornithine transcarbamoylase. The most prominent feature of the spectra is an absorbance difference which resembles a single period of a sine wave spanning the 245-320 nm region with a maximum at approximately 270 nm and a minimum at around 295-300 nm. This broad absorbance difference is typical of a blue-shift 1La band of tryptophan. Superimposed on the broad band in the 275-310 nm region is a series of smaller, narrow peaks resulted from red-shifted 1Lb bands of tryptophan and tyrosine residues. At pH 8.5, only carbamoyl phosphate and its analog phosphonacetamide yield a large ultraviolet difference absorbance (approximately 1800 M-1 cm-1) when bound to the enzyme. The spectra obtained are essentially the same in lineshape to and 80% in intensity of that produced by the bisubstrate analogy, N-(phosphonacetyl)-L-ornithine. In contrast, inorganic phosphate, a product of the reaction, induces small protein absorbance changes (approximately 300 M-1 cm-1) mainly in the 275-310 nm range. When complexed to the free enzyme, L-ornithine yields a marginally discernible ultraviolet difference spectrum in the 275-310 nm region, and its analogs L-norvaline and L citrulline provide no absorbance change. However, inorganic phosphate in combination with any of the L-amino acids produces a difference spectrum similar to that given by carbamoyl phosphate alone. Collectively, these spectra suggest that carbamoyl phosphate elicits an isomerization required for the formation of the ternary complex and are consistent with the compulsory ordered mechanism of the enzyme at pH 8.5 with carbamoyl phosphate being the first substrate bound. Below pH 8, there is a kinetically discernible amount of random binding, but ordered addition is still the preferred pathway (Wargnies B., Legrain, C., and Stalon, V. (1978) Eur J. Biochem. 89, 203-212). Reflecting this change, the difference absorbance of the enzyme bound with carbamoyl phosphate is also pH dependent. The 1La band in the carbamoyl phosphate difference spectrum diminishes by approximately 20% at low pH. The PALO-induced changes, however, are pH invariant suggesting that full extent of the induced-fit isomerization is always reached in the ternary complex. PMID- 2203768 TI - Insulin stimulates the activity of a novel protein kinase C, PKC-epsilon, in cultured fetal chick neurons. AB - In this study we examined the effects of insulin on protein kinase C (PKC) activity in cultured fetal chick neurons. PKC activity, measured as 32P incorporation into histone H1 in the presence of calcium (500 microM), phosphatidylserine (100 micrograms/ml), and diolein (3.3 micrograms/ml) minus the incorporation in the presence of calcium alone, was detected in neuronal cytosolic (207 +/- 33 pmol/min/mg) and membrane (33 +/- 8 pmol/min/mg) fractions. Insulin added to intact neurons increased the activity of PKC in both cytosolic and membrane fractions by about 40%. Neurons preincubated with cycloheximide (10 micrograms/ml) 30 min prior to insulin treatment showed the same degree of stimulation of PKC activity by insulin. The activation of PKC was maximal within 5-10 min of insulin exposure and was sustained for at least 60 min. Insulin stimulated PKC in a dose-dependent manner, with a maximal response obtained at 100 ng/ml. Addition of phosphatidylserine and diolein to neuronal cell extracts resulted in the phosphorylation of four major cytosolic proteins (70, 57, 18, and 16 kDa) and one major membrane protein (75 kDa). Phosphorylation of all five proteins was increased 2-fold in extracts from insulin-treated neurons. Immunoblot analysis of whole cell extracts using antibodies against PKC-alpha, PKC-beta, PKC-gamma, PKC-delta, and PKC-epsilon revealed that cultured fetal chick neurons contained only one of these PKC isoforms, the epsilon-isoform. The enzyme was mostly cytosolic. Insulin had no effect on either the amount of distribution of PKC-epsilon in cultured neurons but induced a small change in the mobility of PKC-epsilon on sodium dodecyl sulfate-polyacrylamide gels. When assay conditions were designed to measure specifically the activity of PKC-epsilon, using a synthetic peptide substrate in the absence of calcium, activity was 50 +/ 12% higher in insulin-treated cells (p less than 0.005). PKC activity in control and insulin treated-neurons was almost completely inhibited when assays included a peptide identical to the pseudo-substrate binding site of PKC-epsilon. We conclude that PKC-epsilon is the major PKC isoform present in cultured fetal chick neurons. Insulin stimulates PKC-epsilon activity by a mechanism that does not involve translocation of the enzyme from cytosol to membrane. PMID- 2203770 TI - ABF1 binding sites in yeast RNA polymerase genes. AB - We have used gel retardation and DNase protection assays to investigate the trans acting factors involved in the regulation of yeast RNA polymerase genes RPC160 and RPC40. The same binding component was found to interact with the promoter of the two genes, at a short distance (100-150 base pairs) from the transcription start sites. From its size, its DNA-binding specificity and its immunological properties, this factor appears to correspond to the autonomous replication sequences and silencer-binding factor ABF1/SBF-B. The interaction of ABF1 with the polymerase upstream box sequence was characterized using gel DNA-binding assay. The factor binds with high affinity to the polymerase upstream box sequence (Kapp = 5.10(-10) M). A mutational analysis showed that nine base pairs belonging to two separated attachment sites are involved in factor binding. The consensus sequence RTCRYB(N)4ACG was derived from the present binding studies. These data provide an experimental basis for evaluating the efficiency of known or potential ABF1 sites and for comparing several factors with ABF1-like binding properties. PMID- 2203769 TI - Characterization of a DL-dityrosine-containing macromolecule from yeast ascospore walls. AB - We have shown previously that the outer layers of yeast ascospore walls contain dityrosine and that this amino acid is a major component of the cross-linked peptides present in the spore wall (Briza, P., Winkler, G., Kalchhauser, H., and Breitenbach, M. (1986) J. Biol. Chem. 261, 4288-4294). We now present evidence that dityrosine is located in the outermost layer and that it is in the DL configuration. Although the proteins (peptides) of the spore wall are insoluble, the macromolecule containing dityrosine can be solubilized by partial acid hydrolysis of spore walls. Analysis of this macromolecule indicates that it contains more than 50 mol% dityrosine and a very limited number of other amino acids. Interestingly, part of the dityrosine of spore walls is present in the DL configuration. We speculate that not only the high degree of cross-links in the outermost layer but also the D-configuration of part of the alpha-C-atoms of dityrosine could contribute to the spores' resistance to lytic enzymes. PMID- 2203772 TI - Minimal deletion of amino acids from the carboxyl terminus of the B subunit of heat-labile enterotoxin causes defects in its assembly and release from the cytoplasmic membrane of Escherichia coli. AB - Minimal alterations at the carboxyl terminus of the B subunit (EtxB) of heat labile enterotoxin from Escherichia coli were found to have a marked effect on the assembly and release of this polypeptide into the periplasm. Nine mutant EtxB polypeptides were obtained by genetic manipulation of the 3'-end of the etxB gene using Bal31 nuclease digestion and codon substitution. A correlation was observed between the magnitude of the changes introduced at the carboxyl terminus and the extent to which the mutant polypeptides were defective in assembly and release. Some of the mutant B subunits, exemplified by those in which the last 2 amino acids had been deleted or in which the last 4 residues had been replaced by three different ones, were found to be only partially defective, with a proportion being associated with the periplasmic face of the cytoplasmic membrane and the remainder being exported to the periplasm. The portion associated with membranes was detected as monomers on sodium dodecyl sulfate-polyacrylamide gels, whereas the portion exported to the periplasm were detected as assembled oligomers. We conclude that the last few amino acids at the carboxyl terminus of EtxB exert a profound influence on the assembly and release of the B subunit from the cytoplasmic membrane during export in E. coli. PMID- 2203771 TI - A subunit of yeast site-specific endonuclease SceI is a mitochondrial version of the 70-kDa heat shock protein. AB - Endo.SceI of Saccharomyces cerevisiae is a heterodimeric site-specific endonuclease, which is distinguishable from prokaryotic restriction endonucleases in the mode of recognition of its cleavage site. We have used monoclonal antibodies specific to the larger subunit (75 kDa) of Endo.SceI to isolate the gene for the subunit (ENS1) from S. cerevisiae. Unexpectedly, ENS1 was found to encode a 70-kDa heat shock protein-related polypeptide and to be identical to recently cloned SSC1. Subcellular fractionation experiments on yeast cells revealed that the primary target site of the larger subunit is mitochondria, where almost all the Endo.SceI activity is localized. Molecular genetic analysis of ENS1 demonstrated its indispensability for growth and the requirement of a high level of its expression at the sporulation and germination stages. The data suggest that ENS1 plays an important role, especially at these differentiation stages. PMID- 2203773 TI - Endotoxin induction of murine metallothionein gene expression. AB - Bacterial endotoxin-lipopolysaccharide (LPS) rapidly induced hepatic metallothionein (MT) mRNA levels in the LPS-sensitive CD-1 strain of mice. This LPS effect was severely attenuated in the LPS-resistant C3H/HeJ strain of mice, but could be mimicked by injection of human recombinant interleukin-1 alpha (IL-1 alpha) or human recombinant tumor necrosis factor (TNF-alpha). In the CD-1 strain, LPS induction of MT gene expression occurred in each of 10 organs examined (liver, kidney, pancreas, intestine, lung, heart, brain, ovary, uterus, and spleen). Solution hybridization with probes specific for MT-I or MT-II mRNA established that these genes were co-induced in each of the organs and that the liver and kidney contained the highest absolute levels of these mRNAs, whereas in the intestine and spleen they were 10-20-fold lower. LPS and cytokine induction of hepatic MT gene expression occurred in hypophysectomized mice, which suggests a lack of significant involvement of glucocorticoids. Several recombinant cytokines (TNF-alpha, IL-1 alpha, IL-1 beta, IL-6, interferon-gamma (IFN-gamma), as well as poly(rI.rC) were effective inducers of hepatic MT-I and MT-II genes. As an attempt to determine which of these cytokines may mediate LPS effects on MT gene expression in vivo, CD-1 mice were injected with LPS or various cytokines, and RNA from liver, ovary, and uterus was extracted at various times postinjection and analyzed by Northern blotting using probes specific for IL-1 alpha, IL-1 beta, TNF-alpha, IL-6, and MT mRNA. In each organ examined, LPS, IL-1 alpha, or IL-1 beta injection caused a rapid, coordinate, transient increase in the levels of each of the cytokine mRNAs which peaked by 1 h and declined to low levels by 4 h. In contrast, levels of MT mRNA did not reach a peak until 4-6 h postinjection. TNF-alpha had minimal effects on expression of cytokine and MT genes in organs other than liver. IL-6 had no effect on hepatic cytokine mRNA levels, and induced MT mRNA only in the liver which suggests a direct effect of IL-6 on hepatic MT gene expression. These data suggest that the acute effects of LPS on MT gene expression may include complex paracrine interactions between a variety of cytokines and the cells expressing MT genes in each organ, and tissue specific cytokine effects on the MT genes. PMID- 2203774 TI - The time-resolved kinetics of superhelical DNA cleavage by BamHI restriction endonuclease. AB - The kinetics of the cleavage of superhelical plasmid DNA (pBR322) by the restriction endonuclease, BamHI, have been analyzed in terms a compartmental model consistent with the chemistry first proposed by Rubin and Modrich (Rubin, R. A., and Modrich, P. (1978) Nucleic Acids Res. 5, 2991-2997) for analysis of the kinetics of the restriction endonuclease, EcoRI. The model was defined in terms of two compartments representing DNA substrate (bound and free), two compartments representing nicked intermediate (bound and free), one compartment representing linear product, and one compartment for free enzyme. A simultaneous analysis of concentration changes over time of the three DNA forms (superhelical, nicked, and linear) at six different enzyme concentrations was undertaken employing this compartmental model using SAAM (Simulation Analysis And Modeling) software. Results showed that rate constants characterizing the association of enzyme with superhelical DNA (6.0 x 10(5) M-1 s-1) and nicked DNA (2.8 x 10(5) M 1 s-1) were similar in magnitude and rate constants characterizing cleavage of the first (1.2 x 10(-2) s-1) and second phosphodiester bonds (3.1 x 10(-2) s-1) were also similar. The analysis yields a kinetically determined equilibrium constant of 12.9 nM for the dissociation of nicked intermediate from the enzyme. The rate constant describing the release of the nicked intermediate from the enzyme has a value of 3.7 x 10(-3) s-1. By comparing the value of this release rate constant to the value of the constant describing the second cleavage event, it can be determined that only 10% of the nicked intermediate bound to the enzyme is released as free nicked DNA and that 90% of the nicked intermediate is processed to the linear form without being released. Hence, most of the DNA is cleaved as the result of a single enzyme-DNA recognition event. No steady state assumptions were made in the analysis. The approach was to directly solve the differential equations which described the kinetic processes using an interactive method. This study demonstrates the usefulness of this approach for the analysis of kinetics of protein-DNA interactions for the restriction endonucleases. PMID- 2203775 TI - DNA structural polymorphism modulates the kinetics of superhelical DNA cleavage by BamHI restriction endonuclease. AB - A compartmental model developed by Hensley (Hensley, P., Nardone, G., Chirikjian, J.G., and Wastney, M. E., (1990) J. Biol. Chem. 265, 15300-15307) for analysis of the time courses of the cleavage of superhelical DNA substrates by the restriction endonuclease, BamHI, has been used to quantify the effects of changes in temperature, ionic strength, superhelical density, and the DNA substrate on the binding and strand cleavage processes. Studies reported here indicate that changes in topology may be introduced into the DNA substrate solely as a result of the plasmid preparation process and in the absence of covalent bond cleavage and ligation. These changes in topology have qualitatively different effects on the kinetics than those promoted by changes in the superhelical density. The former are removed by briefly warming the DNA prior to assay, suggesting that they are only kinetically stable, while the latter changes are not affected by heating. Increasing the [NaCl] from 0.01 M to 0.1 M increases the overall rate of plasmid cleavage by increasing both the rates of cleavage and enzyme DNA association. To describe the decrease in the overall cleavage rate observed in 0.15 M NaCl, an ionic strength-dependent rate-determining structural transition in the DNA substrate was incorporated into the model. The largest changes in the rate of the cleavage process resulted from changes in the DNA substrate. For the SV40 substrate compared to pBR322, the rate constants describing the two association processes and the first bond cleavage event were increased 6- to 7 fold. The rate of the second bond cleavage process was not affected. These changes may be due to differences in the flanking sequences. PMID- 2203776 TI - Mutations that alter the primary structure of type I collagen. The perils of a system for generating large structures by the principle of nucleated growth. PMID- 2203777 TI - A novel metabolic form of the 32 kDa-D1 protein in the grana-localized reaction center of photosystem II. AB - Two forms of the 32 kDa-D1 reaction center protein of photosystem II (PSII), having slightly different mobilities on denaturing polyacrylamide gels, have been resolved in Spirodela oligorrhiza, Glycine max L., Gossypium hirsutum L., Triticum aestivum L., and Zea mays L. The protein band with faster mobility is identified as the 32 kDa-D1 protein, and the less mobile band as a novel form, designated 32*. The two forms are structurally similar based on immunological and partial proteolytic tests. 32* is associated exclusively with the grana and is present in the PSII reaction center. Temporally, 32* appears several hours after the translocation of newly synthesized and processed 32 kDa-D1 protein from the stroma lamellae to the grana. Formation of the 32* is strictly light-dependent under physiological light intensities and correlates with a reciprocal loss of the 32-kDa form. Light induced formation of 32* is inhibited by 3-(3,4 dichlorophenyl)-1,1-dimethylurea but is not coupled to linear electron transport. PMID- 2203778 TI - Biosynthesis of lipid A in Escherichia coli. Acyl carrier protein-dependent incorporation of laurate and myristate. AB - In previous studies we described enzyme(s) from Escherichia coli that transfer two 3-deoxy-D-manno-octulosonate (KDO) residues from two CMP-KDO molecules to a tetraacyldisaccharide-1,4'-bis-phosphate precursor of lipid A, termed lipid IVA (Brozek, K. A., Hosaka, K., Robertson, A. D., and Raetz, C. R. H. (1989) J. Biol. Chem. 264, 6956-6966). The product, designated (KDO)2-IVA, can be prepared in milligram quantities and/or radiolabeled with 32P at position 4' of the IVA moiety. We now demonstrate the presence of enzymes in E. coli extracts that transfer laurate and/or myristate residues from lauroyl or myristoyl-acyl carrier protein (ACP) to (KDO)2-IVA. Thioesters of coenzyme A are not substrates. The cytosolic fraction catalyzes rapid acylation with lauroyl-ACP, but not with myristoyl, R-3-hydroxymyristoyl, palmitoyl, or palmitoleoyl-ACP. The membrane fraction transfers both laurate and myristate to (KDO)2-IVA. Evidence for the enzymatic acylation of (KDO)2-IVA is provided by (a) conversion of [4'-32P](KDO)2 IVA to more rapidly migrating products in the presence of the appropriate acyl ACP, (b) incorporation of [1-14C]laurate or [1-14C]myristate into these metabolites in the presence of (KDO)2-IVA, (c) fast atom bombardment-mass spectrometry, and (d) 1H NMR spectroscopy. At protein concentrations less than 0.5 mg/ml, the acylation of (KDO)2-IVA by the cytoplasmic fraction is absolutely dependent upon the addition of exogenous acyl-ACP. These acyltransferases cannot utilize lipid IVA as a substrate, demonstrating that they possess novel KDO recognition domains. The unusual substrate specificity of these enzymes provides compelling evidence for their involvement in lipid A biosynthesis. Depending on the conditions it is possible to acylate (KDO)2-IVA with 1 or 2 lauroyl residues, with 1 or 2 myristoyl residues, or with 1 of each. PMID- 2203779 TI - Gene-enzyme relationship in the sulfate assimilation pathway of Saccharomyces cerevisiae. Study of the 3'-phosphoadenylylsulfate reductase structural gene. AB - In yeast, mutations in six different loci (MET1, MET4, MET8, MET16, MET22, and MET25) have been reported to result in the absence of 3'-phosphoadenylylsulfate (PAPS) reductase activity. In the present study, we show that MET16 is the structural gene for PAPS reductase and that the yeast and the Escherichia coli enzymes display significant similarities. Thioredoxin has been implicated in the reduction of PAPS in Saccharomyces cerevisiae as well as in E. coli. One of the generally accepted mechanisms for the action of thioredoxin as a hydrogen donor involves a redox-active sulfhydryl group in the catalytic site of PAPS reductase. However, the present study shows that the site-directed mutagenesis of the unique cysteine from PAPS reductase leads to an enzyme which remains active in vivo. This result would rather support the hypothesis of thioredoxin playing the role of a thiol carrier in the reduction of PAPS into sulfite. Strains separately mutated in the six different loci cited above were examined for the expression of different genes. A mutation in the MET4 gene abolishes transcription of both genes MET16 and MET25. In contrast, mutations in MET1, MET8, and MET25 do not impair MET16 transcription, yet strains bearing these mutations are devoid of PAPS reductase activity. To account for the latter result, we postulate that the enzymes involved in sulfate assimilation may occur as a multienzyme complex in S. cerevisiae. PMID- 2203780 TI - Localization of functional domains of the cAMP chemotactic receptor of Dictyostelium discoideum. AB - The topography and functional domains of the cAMP chemotactic receptor of Dictyostelium discoideum were investigated by protease sensitivity to chymotrypsin. Proteolytic digestion of intact cells produced a 23-kDa fragment of the receptor that retained the photoaffinity label used to identify the receptor. Additionally, this fragment contained the sites phosphorylated by CAR-kinase, the enzyme that phosphorylates the ligand-occupied form of the receptor. The fragment was also found to be phosphorylated in response to cAMP stimulation of cells. Proteolytic digestion of either intact cells or membrane preparations did not appreciably alter the binding properties of the receptor, indicating that the domains which determine the cAMP binding pocket are likely to be transmembrane regions of the protein. Additionally, the sensitivity of down-regulated receptors to chymotrypsin digestion suggests that the initial loss of cAMP binding activity upon incubation of cells with high concentrations of ligand does not require receptor internalization. PMID- 2203781 TI - Molecular cloning and heterologous expression of N-glycosidase F from Flavobacterium meningosepticum. AB - N-Glycosidase F (peptide-N4-(N-acetyl-beta-glycosaminyl)asparagine amidase; EC 3.5.1.52) catalyzes the cleavage of N-glycosidically linked carbohydrate chains between N-acetylglucosamine and asparagine. The structural gene was isolated by screening a Flavobacterium meningosepticum genomic DNA library in lambda gt10 with oligonucleotides, deduced from partial amino acid sequences of the protein. A clone with an open reading frame of 1062 bases was obtained. The amino acid sequence reveals a 42-residue-long leader peptide, which shows similarities to the endoglycosidase H-leader with respect to the cleavage site of the signal peptide, but is distinct from the ones known from other Gram-positive or negative bacteria. The molecular weight of the native protein, derived from the DNA sequence, is in agreement with the molecular weight of the purified protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (35,000). Escherichia coli, transformed with a plasmid containing this DNA sequence, expresses N-glycosidase F activity. The enzyme with its natural Flavobacterium promoter and leader peptide is not secreted in E. coli but seems to be associated with cell membranes. PMID- 2203782 TI - Gene cloning of chitinase A1 from Bacillus circulans WL-12 revealed its evolutionary relationship to Serratia chitinase and to the type III homology units of fibronectin. AB - A chitinase gene of Bacillus circulans WL-12 was cloned into Escherichia coli by transforming HB101 cells with a recombinant plasmid composed of chromosomal DNA fragments prepared from B. circulans WL-12 and the plasmid vector pKK223-3. DNA sequencing analysis revealed that the region necessary for the normal expression of chitinase activity contained one open reading frame of 2097 base pairs which codes for the precursor of chitinase A1. The precursor of chitinase A1 contained a long signal sequence of 41 amino acids with an extremely long N-terminal hydrophilic segment of 15 amino acids. Cloned chitinase produced in E. coli had at its N terminus an additional 8 amino acids that were not found in B. circulans mature chitinase A1. The N-terminal two-thirds of the deduced amino acid sequence of chitinase A1 showed a 33% amino acid match to chitinase A of Serratia marcescens. This region of chitinase A1 is immediately followed by tandemly repeating 95-amino acid segments that are 70% homologous to each other. Statistical analysis revealed that these repeating segments are homologous to the type III homology units of fibronectin, a multifunctional extracellular matrix and plasma protein of higher eukaryotes. This observation indicates that type III homology units originated prior to the emergence of eukaryotes and may be distributed in a wide range of organisms. PMID- 2203783 TI - Mechanisms of the stimulation of insulin release by arginine-vasopressin in normal mouse islets. AB - The mechanisms by which arginine-vasopressin (AVP) affects pancreatic B-cell function were studied in normal mouse islets. AVP produced a dose-dependent (0.1 1000 nM; EC50 approximately 1-2 nM) amplification of glucose-induced insulin release. This amplification was of slow onset and reversibility. AVP was ineffective when the concentration of glucose was less than 7 mM, but was still very effective in 30 mM glucose. The increase in insulin release produced by AVP was accompanied by small accelerations of 86Rb and 45Ca efflux from islet cells. Omission of extracellular Ca2+ accentuated the effect of AVP on 86Rb efflux, attenuated that on 45Ca efflux, and abolished that on release. Under no condition did AVP inhibit 86Rb efflux. AVP did not significantly affect cAMP levels, but increased inositol phosphate levels in islet cells, even in the absence of extracellular Ca2+. AVP did not affect the membrane potential in unstimulated B cells and augmented glucose-induced electrical activity only slightly. This was not due to a direct action on ATP-sensitive K+ channels as revealed by patch clamp recordings (whole cell and outside-out patches). In conclusion, AVP is not an initiator of insulin release, but it potently amplifies glucose-induced insulin release in normal mouse B-cells. This effect involves a stimulation of phosphoinositide metabolism, and presumably an activation of protein kinase C, rather than a change in cAMP levels or a direct control of the membrane potential. PMID- 2203785 TI - Tyrosyl free radical formation in the small subunit of mouse ribonucleotide reductase. AB - Each R2 subunit of mammalian ribonucleotide reductase contains a pair of high spin ferric ions and a tyrosyl free radical essential for activity. To study the mechanism of tyrosyl radical formation, substoichiometric amounts of Fe(II) were added to recombinant mouse R2 apoprotein under strictly anaerobic conditions and then the solution was exposed to air. Low temperature EPR spectroscopy showed that the signal from the generated tyrosyl free radical correlated well with the quantity of the Fe(II) added with a stoichiometry of 3 Fe(II) needed to produce 1 tyrosyl radical: 3 Fe(II) + P + O2 + Tyr-OH + H+----Fe(III)O2-Fe(III)-P + H2O. + Tyr-O. + Fe(III), where P is an iron-binding site of protein R2 and Tyr-OH is the active tyrosyl residue. The O-O bond of a postulated intermediate O2(2-)-Fe(III)2 P state is cleaved by the extra electron provided by Fe(II) leading to formation of OH., which in turn reacts with Tyr-OH to give Tyr-O.. In the presence of ascorbate, added to reduce the monomeric Fe(III) formed, 80% of the Fe(II) added produced a radical. The results strongly indicate that each dimeric Fe(III) center during its formation can generate a tyrosyl-free radical and that iron binding to R2 apoprotein is highly cooperative. PMID- 2203784 TI - Intragenic suppressors reveal long distance interactions between inactivating and reactivating amino acid replacements generating three-dimensional constraints in the structure of mitochondrial cytochrome b. AB - Revertants of nonfunctional cytochrome b mutants were isolated and characterized to determine how specific deleterious mutations in cytochrome b can be suppressed by secondary mutations not restoring a wild type protein. It was recently shown that the cytochrome b function can be recovered following various pseudo-wild type reversions at the level of the original site mutation or adjacent positions (di Rago, J.-P., Netter, P., and Slonimski, P. P. (1990) J. Biol. Chem. 265, 3332 3339). In the present study, we describe how the cytochrome b function can be recovered by secondary mutations in positions which are removed from the original mutation by up to more than 100 amino acids. Such revertant mutants are useful for the study of the three-dimensional structure of cytochrome b. The results of the analysis of four deficient mutations which affect a short region of the protein (positions 131-138 of the polypeptide chain) lead us to propose a possible mode of interactive combination between the first five putative transmembrane segments of cytochrome b within the membrane. PMID- 2203786 TI - Direct effects of radiation on the avidin-biotin system. Absence of energy transfer. AB - Frozen solutions of biotinylated glucose-6-phosphate dehydrogenase and fluorescently tagged avidin were exposed to high energy ionizing radiation. Parallel experiments with peroxidase coupled to streptavidin and with biotinylated phycoerythrin were also performed. The loss of function of each compound was analyzed according to target theory. Target analysis revealed that the radiation-sensitive mass associated with the enzymatic activity and that associated with the fluorescence were unchanged by irradiation in the strongly coupled state. Therefore the noncovalent bonds between biotin and avidin do not permit the transfer of radiation-deposited energy in amounts sufficient to destroy the activity of apposing molecule. PMID- 2203787 TI - The activity of one soluble component of the cell-free NADPH:O2 oxidoreductase of human neutrophils depends on guanosine 5'-O-(3-thio)triphosphate. AB - Neutrophil NADPH:O2 oxidoreductase activity, essential in the killing of bacteria by neutrophils, can be elicited in a cell-free system that requires plasma membranes, cytosol and sodium dodecyl sulfate. In addition, GTP or its nonhydrolyzable analog guanosine 5'-3-O-(thio)triphosphate (GTP gamma S) enhances NADPH oxidase activity. We investigated the mechanism of this effect of GTP gamma S in the cell-free system. Cytosol from human neutrophils was separated in three different soluble oxidase components (SOC I, SOC II, and SOC III). Previously we (Bolscher, B. G. J. M., Van Zwieten, R., Kramer, I. J. M., Weening, R. S., Verhoeven, A. J., and Roos, D. (1989) J. Clin. Invest. 83, 757-763) reported that the cytosol contains two components which act synergistically. We now report that one component (previously labeled SOC II) contains two different components that can be separated by ion exchange chromatography. Immunoblotting with antiserum B 1 (Volpp, B. D., Nauseef, W. M., and Clark, R. A. (1988) Science 242, 1295-1297), directed against a cytosolic complex capable of activating latent membranes in the cell-free system, showed a 47-kDa protein in SOC II and a 67-kDa protein in SOC III. SOC II also contains the 47-kDa phosphoprotein, which indicates that this phosphoprotein and the protein recognized by the antiserum are identical. Low rates of NADPH-dependent O2 consumption can be elicited by SOC II and SOC III in the absence of SOC I. This activity is independent of GTP gamma S. Addition of SOC I increases this activity 3-4-fold, only when GTP gamma S is present. Plasma membranes, incubated with SOC I plus GTP gamma S and re-isolated, showed a similar 3-4-fold enhanced O2 consumption with SOC II and SOC III. The GTP gamma S effect is exerted primarily at the level of the plasma membrane. The concentration of GTP gamma S that causes a half-maximal stimulation was 0.4 mu M. It is concluded that SOC I is a functional component of the NADPH oxidase. PMID- 2203788 TI - Cloning of ubiquitin activating enzyme from wheat and expression of a functional protein in Escherichia coli. AB - The initial step in the conjugation of ubiquitin to substrate proteins involves the activation of ubiquitin by ubiquitin activating enzyme, E1. Previously, we purified and characterized multiple species of E1 from wheat germ. We now describe the isolation and characterization of a cDNA clone encoding E1 from wheat. This clone (UBA1) was isolated from a cDNA expression library with anti wheat E1 antibodies. It contained an open reading frame coding for 1051 amino acids and directed the synthesis of a protein that comigrated with a wheat germ E1 of 117 kDa. UBA1 was confirmed as encoding E1 by (i) comparison of the peptide map of the protein product of UBA1 synthesized in Escherichia coli with that of purified E1 from wheat, and (ii) amino acid sequence identity of peptides generated from purified E1 with regions of the derived amino acid sequence of UBA1. The isolation of two additional cDNAs closely related to UBA1 indicated that E1 was encoded by a small gene family in wheat. Nonetheless, a single poly(A+) mRNA size class of 4 kilobases hybridized with UBA1. When expressed in E. coli, the product of UBA1 catalyzed the formation of a thiol ester linkage between ubiquitin and an ubiquitin carrier protein. The ability of E. coli containing UBA1 to synthesize an active protein will allow us to identify domains important for E1 function using in vitro mutagenesis. PMID- 2203789 TI - Protein synthesis in yeast. Structural and functional analysis of the gene encoding elongation factor 3. AB - The yeast translational elongation factor 3 (EF-3) stimulates EF-1 alpha dependent binding of aminoacyl-tRNA by the ribosome. The requirement for EF-3 is unique to fungi; a functional analog has not been found in prokaryotes or other eukaryotes. We have isolated and characterized the structural gene, YEF3, that encodes EF-3. The YEF3 gene is present in one copy/haploid genome and is essential for vegetative growth. DNA sequence analysis revealed that the YEF3 gene contains an open reading frame of 1044 codons. The deduced amino acid sequence contains two repeats of a nucleotide-binding motif, which is similar to the nucleotide-binding consensus sequences of hydrophilic, membrane-associated ATPases. EF-3 catalyzes ATP hydrolysis in a ribosome-dependent manner. A modified assay procedure has been developed that allows measurement of the ATP hydrolytic activity of EF-3 in cell-free extracts without interference by other nucleotide hydrolyase activities. Using this modified assay, we have shown that the wild type YEF3 gene restores heat stable EF-3 activity in a yeast strain containing a temperature-sensitive EF-3. Introduction of the YEF3 gene on a high copy number plasmid into yeast strains increases the ribosome-dependent ATPase activity. The level of EF-3 protein is also increased 3-5-fold. Elevated EF-3 protein levels did not cause a significant increase in EF-1 alpha and EF-2 protein. Yeast strains containing elevated EF-3 protein levels are more sensitive to the aminoglycoside antibiotics hygromycin and paromomycin. These drugs are known to increase translational errors. This observation suggests that EF-3 may indirectly affect translational accuracy. PMID- 2203790 TI - Amino acid and cDNA sequence of bovine phosducin, a soluble phosphoprotein from photoreceptor cells. AB - Vertebrate photoreceptor cells contain a soluble phosphoprotein, phosducin, which complexes with the beta, gamma subunits of the GTP-binding protein, transducin. Light-induced changes in cyclic nucleotide levels modulate the phosphorylation of phosducin by protein kinase A. The complete amino acid sequence of purified phosducin from bovine retinas was determined by Edman degradation from overlapping polypeptides derived from enzymatic digestion by trypsin and Staphylococcus aureus V8 protease or from chemical degradation by cyanogen bromide. Excluding the unidentified group which blocks the NH2 terminus, phosducin contains 245 amino acids with a calculated molecular weight of 28,185 and isoelectric point of pH 4.5. Phosducin is enriched with acidic and sulfur containing amino acids, having 32 glutamic acid, 16 aspartic acid, 9 methionine, and 5 cysteine residues. It also contains 24 serine and 8 threonine residues, of which only serine 73 is located within a consensus phosphorylation sequence ( RKMS(P)QV-) for cyclic nucleotide-dependent protein kinase. Secondary structure analysis predicts the presence of 62% alpha-helix, 22% beta-sheet, and 16% random coil, with eight turns. Computer-aided searches of protein data banks revealed no apparent homology to any sequenced protein except that coded by a MEKA cDNA clone (Kuo, C-H., Akiyama, M., and Miki, N. (1989) Mol. Brain Res. 6, 1-10) which deviates from the confirmed phosducin sequence in the last 15 amino acids. Sequence analysis of a cDNA clone for bovine retinal phosducin confirmed that the MEKA clone deviation resulted from an unidentified cDNA guanosine nucleotide, a shifted reading frame and a premature stop codon. PMID- 2203791 TI - Genes required for formation of the apoMoFe protein of Klebsiella pneumoniae nitrogenase in Escherichia coli. AB - A binary plasmid system was used to produce nitrogenase components in Escherichia coli and subsequently to define a minimum set of nitrogen fixation (nif) genes required for the production of the iron-molybdenum cofactor (FeMoco) reactivatable apomolybdenum-iron (apoMoFe) protein of nitrogenase. The active MoFe protein is an alpha 2 beta 2 tetramer containing two FeMoco clusters and 4 Fe4S4 P centers (for review see, Orme-Johnson, W.H. (1985) Annu. Rev. Biophys. Biophys. Chem. 14, 419-459). The plasmid pVL15, carrying a tac-promoted nifA activator gene, was coharbored in E. coli with the plasmid pGH1 which contained nifHDKTYENXUSVWZMF' derived from the chromosome of the nitrogen fixing bacterium Klebsiella pneumoniae. The apoMoFe protein produced in E. coli by pGH1 + VL15 was identical to the apoprotein in derepressed cells of the nifB- mutant of K. pneumoniae (UN106) in its electrophoretic properties on nondenaturing polyacrylamide gels as well as in its ability to be activated by FeMoco. The constituent peptides migrated identically to those from purified MoFe protein during electrophoresis on denaturing gels. The concentrations of apoMoFe protein produced in nif-transformed strains of E. coli were greater than 50% of the levels of MoFe protein observed in derepressed wild-type K. pneumoniae. Systematic deletion of individual nif genes carried by pGH1 has established the requirements for the maximal production of the FeMoco-reactivatable apoMoFe protein to be the following gene products, NifHDKTYUSWZM+A. It appears that several of the genes (nifT, Y, U, W, and Z) are only required for maximal production of the apoMoFe protein, while others (nifH, D, K, and S) are absolutely required for synthesis of this protein in E. coli. One curious result is that the nifH gene product, the peptide of the Fe protein, but not active Fe protein itself, is required for formation of the apoMoFe protein. This suggests the possibility of a ternary complex of the NifH, D, and K peptides as the substrate for the processing to form the apoMoFe protein. We also find that nifM, the gene which processes the nifH protein into Fe protein (Howard, K.S., McLean, P.A., Hansen, F. B., Lemley, P.V., Kobla, K.S. & Orme-Johnson, W.H. (1986) J. Biol. Chem. 261, 772-778) can, under certain circumstances, partially replace other processing genes (i.e. nifTYU and/or WZ) although it is not essential for apoMoFe protein formation. It also appears that nifS and nifU, reported to play a role in Fe protein production in Azotobacter vinelandii, play no such role in K. pneumoniae, although these genes are involved in apoMoFe formation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2203792 TI - Isolation of two isoforms of a novel 15-kDa protein from rabbit polymorphonuclear leukocytes that modulate the antibacterial actions of other leukocyte proteins. AB - We have recently reported the use of the highly selective and reversible binding of the potent bactericidal/permeability-increasing protein (BPI) to target Gram negative bacteria (Escherichia coli) for its isolation from crude extracts of human polymorphonuclear leukocytes (PMN). We now report the use of the same procedure for the purification from rabbit PMN of BPI and also of a novel 15-kDa species that consists of two nearly identical isoforms. These 15-kDa proteins have no demonstrable antibacterial activities by themselves. However, one isoform (p15A) potentiates strongly and the other (p15B) weakly the early antibacterial effects of both rabbit and human BPI. Both isoforms inhibit the late lethal action of BPI. Whereas the potentiating effect is specific for BPI the inhibitory effect is seen also with another antibacterial protein of PMN granules, azurocidin. Thus, we have identified in rabbit PMN a previously unrecognized 15 kDa protein species that may modulate during phagocytosis the antimicrobial effects of BPI (and other granule proteins). PMID- 2203793 TI - Primary structure of the yeast choline transport gene and regulation of its expression. AB - The yeast Saccharomyces cerevisiae possesses a choline transport system encoded by the CTR gene. Incorporated choline is exclusively utilized for the synthesis of phosphatidylcholine. Determination of the complete nucleotide sequence of the CTR gene showed that the deduced primary sequence of the choline transporter comprised 563 amino acid residues with a calculated molecular weight of 62,055. Both the amino- and carboxyl-terminal regions were hydrophilic whereas the rest of the sequence was highly hydrophobic and contained several membrane-spanning regions. There were four potential glycosylation sites in the hydrophilic parts of the sequence. The transporter showed significant sequence similarities to the yeast arginine and histidine transporters. A 2.0-kilobase RNA species was identified as the CTR transcript. Disruption of the CTR locus completely abolished the choline transport activity, indicating that the CTR product is the sole choline transporter in yeast. The regulation of choline transport mRNA was investigated by Northern blot analysis using a CTR probe. The abundance of CTR mRNA significantly decreased on incubation of cells with a combination of choline and myo-inositol. The CTR mRNA level was high in the exponential growth phase but decreased dramatically when cells entered the stationary phase. Similar control had been observed for some enzymes in yeast phospholipid synthesis. PMID- 2203794 TI - Detection of surface-adsorbed (lipo)proteins by means of a two-step enzyme immunoassay: a study on the Vroman effect. AB - In view of reports on the involvement of high-molecular-weight (HMW) kininogen and high-density lipoprotein (HDL) in the Vroman effect, we studied the adsorption of fibrinogen, HMW kininogen, HDL and several other proteins from pooled human plasma and congenitally HMW kininogen-deficient plasma onto glass and low-density polyethylene, both as a function of the plasma concentration and the contact time. Mixtures of purified (lipo)proteins were also included in the study. Protein adsorption was determined by means of a two-step enzyme immunoassay. Our results support the hypothesis that HMW kininogen is involved in the displacement of fibrinogen, which is almost instantly adsorbed from normal plasma onto glass. On hydrophobic polymers like polyethylene, the low amounts of adsorbed fibrinogen and HMW kininogen from plasma and concentrated plasma solutions may be due to a preferential adsorption of HDL. PMID- 2203796 TI - Clinical review 12: The use and misuse of the sensitive thyrotropin assays. PMID- 2203795 TI - Adhesive bonding of denture base resins to plastic denture teeth. AB - The adhesive bonding of denture teeth to denture base resins in dentures with conventional acrylic teeth and crosslinked plastic teeth was investigated. The dentures with highly crosslinked plastic teeth such as SR-Orthosit, Crystal ND, and Mitel-OM showed poor bonding at the tooth/base resin interface using the conventional bonding method. Elimination of the alginate mold lining material in the conventional bonding method effectively improved bonding at the tooth/base resin interface. The application of 4-META adhesive bonding agents to the denture teeth improved the interface bonding of highly crosslinked plastic teeth and the denture base. Dentures with Orthosit and Mitel showed differences in bonding ability when two different adhesives were used. PMID- 2203797 TI - Correlation of urinary albumin and beta-2-microglobulin and growth hormone excretion in patients with diabetes mellitus and short stature. AB - We examined the correlation between urinary GH, urinary albumin, and beta-2 microglobulin excretion to determine how the excretion of GH relates to markers of renal glomerular and tubular function. Urinary albumin and GH excretion was determined in timed daytime and nighttime urine collections obtained from both subjects with diabetes mellitus and subjects with short stature. For subjects with diabetes, urinary GH excretion rate correlated highly with urinary albumin concentration and excretion rate in both the range of 0 to 1.6 g/L (r = 0.75), P less than 0.001) and in the microalbuminuria range, 0 to 0.4 g/L (r = 0.53, P less than 0.001). Changes in GH and albumin excretion occurred in parallel in 71% of the subjects with diabetes and elevated albumin excretion. The mean GH excretion rate was higher in the group with elevated albumin excretion rate (AER) during both day and night compared to the group with microalbuminuria during the day and normal AER at night. For subjects with short stature, the mean albumin excretion rate was 0.7 +/- 1.3 micrograms/min (range 0.05-8.3 micrograms/min) using a sensitive enzyme-linked immunosorbent assay to measure albumin concentration. The correlation of GH and albumin excretion rates for the subjects with short stature was not statistically significant (r = 0.14, P less than 0.5). About half of the subjects with diabetes and elevated AER (greater than 10 micrograms/min) had a GH excretion rate within the range observed in subjects with short stature. The GH and albumin excretion rate were not correlated in this group. There was a positive correlation of both albumin and GH excretion rate with age in the subjects with diabetes. Urinary GH and beta-2-microglobulin excretion rates were determined in a larger group of subjects with diabetes and a separate group with short stature. Urinary GH and beta-2-microglobulin excretion were correlated both in subjects with diabetes (r = 0.46, P less than 0.001) and with short stature (r = 0.64, P less than 0.001). The association was present in urine collected either during the day or night. The mean GH excretion rate of the group with diabetes was greater than the group with short stature. In conclusion, there was an association of urinary GH and albumin excretion rate in subjects with abnormal glomerular function as indicated by elevated albumin excretion rate. An association of urinary GH and beta-2-microglobulin excretion was observed in subjects with normal tubular function.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2203798 TI - Intrauterine diagnosis and treatment of fetal goitrous hypothyroidism. AB - Newborn screening programs for the detection of congenital hypothyroidism have dramatically shortened the time before treatment is begun. However, concern still exists about central nervous system sequelae which may persist due to a period of untreated intrauterine hypothyroidism. Presence of polyhydramnios led to the ultrasound diagnosis of a fetal goiter. Hypothyroidism was confirmed at 34 weeks gestation by percutaneous fetal blood sampling, which revealed an elevated TSH (186 mU/L) and a low T4 (19.3 nmol/L). Intraamniotic fluid injections of 500 micrograms levothyroxine sodium (T4) every 10-14 days increased fetal serum T4 (59.2 nmol/L), decreased fetal serum TSH (14 mU/L), decreased amniotic fluid TSH, and decreased the size of the fetal goiter. The infant was born at term without perinatal complications. Thyroid function studies on cord blood were normal (T4, 109.4 nmol/L; TSH, 1.3 mU/L), and the infant was discharged on oral T4. Follow-up examination at age 6 weeks revealed that the infant was developmentally normal and clinically and chemically euthyroid. Intrauterine T4 therapy can suppress fetal TSH and treat fetal hypothyroidism despite hypothyroid levels of serum T3. Highly sensitive TSH assays may allow the use of amniotic fluid TSH as a marker for fetal hypothyroidism. PMID- 2203800 TI - Modulation of HLA-DR expression in epithelial cells by interleukin 1 and estradiol-17 beta. AB - Both ultrapure human interleukin-1 (IL-1) and Escherichia coli derived recombinant IL-1 alpha and beta consistently induced the expression of major histocompatibility class II (HLA-DR) molecules in a human endometrial and a breast carcinoma cell line. [35S]Methionine incorporation into IL-1 induced, immunoprecipitable HLA-DR molecules demonstrated de novo synthesis of both light and heavy chains of the HLA-DR molecules. Lipopolysaccharide, recombinant interleukin-2 and recombinant interleukin-6 failed to induce HLA-DR expression in these epithelial cells. In contrast to the dramatic effect on HLA-DR expression, IL-1 had no effect on the epithelial cell proliferation. Pretreatment of T47D cells with estradiol-17 beta significantly decreased the IL-1 induced HLA-DR expression, and pretreatment of IL-1 with an IL-1 specific antibody, neutralized IL-1 action. These studies demonstrate that a cytokine (IL-1) and a sex steroid hormone estradiol-17 beta can interact to regulate the expression of HLA-DR molecules in epithelial cells. PMID- 2203799 TI - A comparative and longitudinal study on endocrine changes related to ovarian function in patients with anorexia nervosa. AB - Screening of androgens and estrogens in blood and a GnRH test were performed in 20 female patients with anorexia nervosa and in 10 lean and 10 normal weight healthy control subjects. Both control groups had regular ovulatory menstrual cycles. The investigation was performed in the mid-follicular phase. Several variables showed significant differences between the groups; the levels of PRL, estrone, estradiol, progesterone, testosterone, androstenedione, and LH were lowest in the patients with anorexia nervosa. The lean control group showed intermediate values for progesterone, androstenedione, and, to a smaller extent, testosterone. The FSH response to GnRH was significantly higher in the patient group, corresponding to the pattern of late prepubertal girls. Ten patients were seen in a follow-up study. Five had resumption of the menstrual cycle, and the others still had amenorrhea. The two subgroups did not differ in either weight gain or the basal hormonal variables investigated. After weight gain an increased LH response to GnRH was observed in both subgroups. Patients who had resumption of the menstrual cycle showed a higher response of LH to GnRH, both before and after weight gain. The mean increase in LH after GnRH administration was significantly different between the two subgroups. The results suggest that the GnRH test may be useful to assess the stage of the disease and to predict the outcome, especially with regard to restoration of the menstrual cycle. PMID- 2203801 TI - Immunohistological distribution of the secretory endometrial protein, 'pregnancy associated endometrial alpha 2-globulin', a glycosylated beta-lactoglobulin homologue, in the human fetus and adult employing monoclonal antibodies. AB - We have previously demonstrated that pregnancy-associated endometrial alpha 2 globulin (alpha 2-PEG), the human glycosylated beta-lactoglobulin homologue (HG BLG), is quantitatively the major secretory soluble protein product of the secretory endometrium during the latter half of the menstrual cycle and decidua spongiosa of the gestational endometrium during early pregnancy, and is principally localized to the glandular epithelium. In the present study employing monoclonal antibodies in immunohistological techniques, the distribution and localization has been examined in normal and pathological tissues of the adult and first-trimester fetus. No significant staining for alpha 2-PEG was detected in any nonreproduction-associated tissue in the normal adult nor any tissue in the fetus. In the adult, most intense staining was associated with the endometrial glandular epithelium in the uterus or in ectopic sites in patients with endometriosis. During the menstrual cycle and pregnancy, appearance of alpha 2-PEG in endometriosis was strongly linked with its appearance in uterine endometrial tissue, suggesting that endometriotic tissue exhibited competence to respond to the same hormonal milieu required to induce synthesis in the uterine endometrium. Localization to the mucosal epithelium of the Fallopian tube was consistent with synthesis of alpha 2-PEG, albeit at low levels, and staining at this site reflected fluctuations of staining within the uterus. Of the pathological specimens examined, staining was only detected in a proportion of ovarian carcinomas. No staining was detected in the mammary gland, a site of beta lactoglobulin synthesis, whether obtained during pregnancy or lactation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203803 TI - Cytogenetic studies in couples experiencing repeated pregnancy losses. AB - A computerized database generated from the literature on cytogenetic studies in couples experiencing repeated pregnancy losses has been set up at the University of Quebec at Chicoutimi. At the present time, it contains data on 22,199 couples (44,398 individuals). The statistical analyses showed a relationship between the distribution of the chromosome abnormalities and the number of abortions. An uneven distribution of the chromosomal structural rearrangements according to the sex of the carrier was found (P less than 0.05). Overall, 4.7% of the couples ascertained for two or more spontaneous abortions included one carrier. It also appeared that only translocations (both reciprocal and Robertsonian) and inversions were associated with a higher risk of pregnancy wastage. Therefore, genetic counselling should be offered to these couples and investigations performed on their extended families. PMID- 2203802 TI - Development of antisperm contraceptive vaccine for humans: why and how? PMID- 2203804 TI - Preliminary results on transvaginal tubal embryo stage transfer (TV-TEST) without ultrasound guidance. AB - IVF procedures have been increasingly used in male subfertility for both therapeutic and diagnostic purposes. As we assume a positive influence of the tubal milieu on the early embryonal development, any therapy should aim at intratubal embryo transfer. In this respect, only invasive techniques such as laparoscopy or laparotomy have been available hitherto (Asch et al., 1986; Balmaceda et al., 1988; Diedrich et al., 1989). Transvaginal intra-tubal embryo stage transfer (TV-TEST) was performed in 15 patients. After stimulation with clomiphene/HMG, HMG or GnRHA/HMG, patients with a follicle size of 18 mm were given 10000 IU HCG. Thirty six hours later, the transvaginal oocyte retrieval was performed without anaesthesia. Altogether, 109 oocytes were recovered. A fertilization rate of 30.3% yielded 33 embryos. Forty-eight hours after oocyte retrieval, the TV-TEST was performed without anaesthesia, in the course of which a maximum of three embryos in the 2- to 8-cell stage were transferred into one tube. Six of these patients are now pregnant. PMID- 2203805 TI - The effects of the antiprogestin mifepristone, in vivo, and progesterone in vitro on prolactin production by the human decidua in early pregnancy. AB - This study investigated the regulatory effect of progesterone on decidual prolactin (dPRL) production during early human pregnancy (6-7 weeks). Patients (n = 7) were treated with the antiprogestin-mifepristone (RU 486; 600 mg single oral dose) for 24-36 h before termination of pregnancy by curettage. Tissue was also obtained from patients without pretreatment in vivo (n = 8) and acted as controls. Decidual tissue was incubated in vitro with and without progesterone and mifepristone for 5 days and the medium changed daily. Prolactin production by decidua parietalis decreased over the period of incubation and was unaffected by addition of progesterone or mifepristone. However, in the group pretreated in vivo with mifepristone, the production of dPRL was markedly lower than in the control group. In contrast, the production of dPRL by decidua capsularis to which trophoblast was attached, was maintained at a constant level over 5 days of culture and was unaffected by pretreatment with mifepristone in vivo or its addition in vitro, or by progesterone. Prolactin was immunolocalized using avidin biotin immunoperoxidase staining to decidualized cells within the decidua and the intensity of staining was reduced or absent in the decidua parietalis from the mifepristone group compared to controls, but was similar in decidua capsularis in both control and mifepristone groups, in good agreement with the in-vitro production of dPRL. Our findings suggest that the effect of progesterone may be only facilitative, maintaining decidual differentiation, and dPRL production might only be associated with the presence of progesterone-dependent differentiated decidual cells. Apart from progesterone, factors from trophoblast cells can maintain dPRL production during pregnancy. PMID- 2203807 TI - Identification of various serovar strains of Mycobacterium avium complex by using DNA probes specific for Mycobacterium avium and Mycobacterium intracellulare. AB - Reference strains of the Mycobacterium avium complex (MAC) belonging to serovars 1 to 28 were examined with DNA probes (Gen Probe Rapid Diagnostic System for the MAC; Gen Probe Inc., San Diego, Calif.) specific for either M. avium or Mycobacterium intracellulare. This study revealed that the earlier designations of the MAC serovars, in which serovars 1 to 3 and 4 to 28 were regarded as M. avium and M. intracellular, respectively, should be revised as follows. First M. avium includes serovars, 1 to 6, 8 to 11, and 21. Second, M. intracellulare includes serovars 7, 12 to 20, and 25. However, other serovars, such as serovars 22 to 24 and 26 to 28, involve M. intracellulare, Mycobacterium scrofulaceum, and MAC that are lacking in the reactivity with either DNA probe and that are too disordered to enable a conclusive description here, particularly concerning their taxonomic positions in the MAC. PMID- 2203806 TI - The Spanish law governing assisted reproduction techniques: a summary. PMID- 2203808 TI - Processing and microfiltration of mosquitoes for malaria antigen detection in a rapid dot immunobinding assay. AB - Data on a technique for the detection of antigen from arthropod vectors in a dot immunobinding assay are presented. In this system, antigen present in the vector was first solubilized in sodium dodecyl sulfate. The homogenate from this process was microfiltered through a two-membrane sandwich; target antigen molecules passed through the first membrane and were immobilized on the second one. The first membrane was nonbinding and served to impinge debris. The second membrane was a high-protein-binding-capacity hydrophobic polyvinylidene difluoride membrane. High signal-to-noise ratios were produced by this method, which is readily adaptable for field use. This assay was used for malaria sporozoites, but it can serve as a general technique that is applicable to other arthropod vectors and etiologic agents. PMID- 2203809 TI - Evaluation of the Captia enzyme immunoassays for detection of immunoglobulins G and M to Treponema pallidum in syphilis. AB - Two new enzyme-linked immunosorbent assays (ELISA), one for the measurement of immunoglobulin G (IgG) (Captia Syphilis-G) and one for the measurement of IgM (Captia Syphilis-M), were evaluated for detecting antibodies to Treponema pallidum. Serum samples from 169 patients, 96 with various stages of untreated syphilis, 63 with treated syphilis, and 10 who were noninfected, were investigated. All sera were also examined by traditional treponemal and cardiolipin tests and by the fluorescent treponemal antibody absorption (FTA-ABS) test for 19S(IgM). The overall sensitivity of Captia Syphilis-G was 98.3%. The IgG ELISA was very sensitive (100%) in all stages of untreated syphilis, except in primary syphilis (82%). In all diagnostic groups of syphilis, the reactivity of Captia Syphilis-M was similar to that of the 19S(IgM) FTA-ABS test, except in reinfections, in which the IgM capture ELISA was less sensitive. False-positive IgM capture ELISA results were not found in the 10 neonates born to mothers adequately treated for syphilis. However, of six serum samples containing rheumatoid factor, two were reactive in the Captia Syphilis-M test but not in the 19S(IgM) FTA-ABS test. This indicated that the specificity of the IgM capture ELISA was not absolute. All serum samples from treated patients were reactive in the IgG ELISA, but only 15 samples were reactive in the IgM capture ELISA, which appeared to be as effective as the 19S(IgM) FTA-ABS test in monitoring the effect of treatment. Simultaneous measurement of IgG and IgM antibodies for T. pallidum by the Captia immunoassays appears to be an efficient and simple method for confirming the diagnosis of syphilis as well as for indicating whether active disease is present. PMID- 2203810 TI - Comparison of two enzyme immunoassays to culture for the diagnosis of chlamydial conjunctivitis and respiratory infections in infants. AB - Data are limited for the performance of enzyme immunoassays for the detection of Chlamydia trachomatis in conjunctival and nasopharyngeal specimens from infants. The only available data are for one assay, Chlamydiazyme (Abbott Diagnostics). The purpose of this study was to compare a new enzyme immunoassay, Pathfinder (Kallestad Diagnostics), with Chlamydiazyme and culture for the diagnosis of chlamydial conjunctivitis and pneumonia in infants. Pathfinder differs from Chlamydiazyme in that it uses a monoclonal antibody directed against the chlamydial lipopolysaccharide in addition to a polyclonal antichlamydial antibody. Triplicate conjunctival and nasopharyngeal specimens were obtained from 97 infants with conjunctivitis, and additional nasopharyngeal specimens were obtained from 14 infants with suspected chlamydial pneumonia (total, 111 nasopharyngeal specimens). Twenty-nine (30%) of the conjunctival specimens from infants with conjunctivitis and four (28.6%) of the nasopharyngeal specimens from the infants with pneumonia were positive for C. trachomatis by cell culture. The sensitivities, specificities, and positive and negative predictive values for Pathfinder for conjunctival specimens were 96.6, 98.5, 96.6, and 98.5%, respectively. The results for Chlamydiazyme were 96.6, 100, 100, and 98.6%, respectively. For nasopharyngeal specimens, the results for Pathfinder were 77.8, 94.6, 73.7, and 95.7%, respectively. The results for Chlamydiazyme were 66.7, 95.7, 75, and 93%, respectively. Pathfinder and Chlamydiazyme appeared to perform equivalently for the detection of C. trachomatis in both eye and nasopharyngeal specimens from infants with chlamydial conjunctivitis and pneumonia. PMID- 2203811 TI - Detection of specific immunoglobulin E in patients with toxoplasmosis. AB - An immunocapture assay was developed to detect Toxoplasma gondii-specific immunoglobulin E (IgE) in sera from adults with acute acquired infection or reactivation and from babies with congenital toxoplasmosis. The components of this assay were monoclonal antibody to human IgE, samples from patients, and T. gondii tachyzoites treated with Formalin. When T. gondii-specific IgE antibodies were present, visually detectable agglutination occurred. Sera, umbilical cord blood, fetal blood, cerebrospinal fluid, and amniotic fluid were tested by this method. Specific IgE antibodies were detected in sera from 25 (86%) of 29 adults who developed specific IgG antibody during pregnancy or had specific IgA and IgM antibodies. Specific IgE was present early during infection, at the time that IgM antibodies were present, and slightly preceding the presence of specific IgA antibodies. In 23 patients tested serially, IgE antibodies never persisted for longer than 4 months. No nonspecific anti-T. gondii IgE was detected in sera from uninfected individuals. Maternal IgE antibodies did not cross the placenta. In sera of patients with congenital toxoplasmosis, specific IgE antibodies were found at birth, during the first year of life, and during immunologic recrudescence following discontinuation of pyrimethamine-sulfonamide therapy. The IgE immunocapture assay is simple to perform. It is especially useful for determining when T. gondii was acquired by recently infected pregnant women. PMID- 2203812 TI - Detection and identification of mycobacteria by amplification of rRNA. AB - Oligonucleotides specific at a genus, group, or species level were defined by a systematic comparison of small-subunit rRNA sequences from Mycobacterium tuberculosis, M. bovis, M. africanum, M. bovis BCG, M. avium, M. kansasii, M. marinum, M. gastri, M. chelonae, M. smegmatis, M. terrae, M. nonchromogenicum, M. xenopi, M. malmoense, M. szulgai, M. scrofulaceum, M. fortuitum, M. gordonae, M. intracellulare, M. simiae, M. flavescens, M. paratuberculosis, M. sphagni, M. cookii, M. komossense, M. phlei, and M. farcinica. On the basis of the defined oligonucleotides, the polymerase chain reaction technique was explored to develop a sensitive taxon-specific detection system for mycobacteria. By using M. tuberculosis as a model system, fewer than 10 bacteria could be reliably detected by this kind of assay. These results suggest that amplification of rRNA sequences by the polymerase chain reaction may provide a highly sensitive and specific tool for the direct detection of microorganisms without the need for prior cultivation. PMID- 2203813 TI - Interlaboratory and intralaboratory comparisons of indirect immunofluorescence assays for serodiagnosis of Lyme disease. AB - A conventional indirect immunofluorescence assay (IFA) and an anticomplement indirect immunofluorescence assay (ACIF) for detecting serum antibodies to Borrelia burgdorferi in humans were evaluated during a prevalence survey in northern California. Sera obtained from 119 current or former residents of an area in which Lyme disease is endemic were split and tested by the IFA in two laboratories and the ACIF in a third. The seropositivity rate ranged from 15 to 20% with 88 to 93% agreement among laboratories. Interlaboratory agreement was statistically highly significant in each of the three pairwise comparisons and was positively associated with clinical manifestations of Lyme disease. Intralaboratory agreement ranged from 93 to 96% in two laboratories and was also statistically highly significant. Immunoblotting confirmed 100 of 101 of the nondiscrepant immunofluorescence test results and likewise was positively correlated with the degree of interlaboratory agreement. The ACIF was found to be a highly specific test (100% specificity) with a much lower cutoff titer (1:8) than the conventional IFA (determined to be 1:128 or 1:256 in two laboratories) for detecting antibodies to B. burgdorferi. It also appeared to be more sensitive (80 versus 68%) than the IFA as determined by comparative immunoblotting, though the absolute sensitivity of the ACIF for serodiagnosis of early Lyme disease has yet to be determined. Significant serologic cross-reactivity was demonstrated between B. burgdorferi, Borrelia coriaceae, and Borrelia hermsii by the IFA, which may confound spirochetal serosurveys in California where all three spirochetes are known to coexist. PMID- 2203814 TI - Comparison of human immune responses to purified Vero cell and human diploid cell rabies vaccines by using two different antibody titration methods. AB - Antibody responses to a conventional rabies preexposure regimen of a new purified Vero cell rabies vaccine (PVRV) and a human diploid cell vaccine (HDCV) were compared in 80 healthy Kenyan veterinary students. Forty-three of the students received the PVRV and 37 received the HDCV on days 0, 7, and 28. Antibody responses were monitored by using the rapid fluorescent-focus inhibition test (RFFIT) and an inhibition enzyme immunoassay (INH EIA) on days 0, 7, 28, and 49. Both vaccines elicited a rapid antibody response. A good correlation between the RFFIT titers and the INH EIA titers was obtained (r = 0.90). Our results also showed that the INH EIA was more reproducible and might therefore be a suitable substitute for the more expensive and less reproducible RFFIT. The geometric mean titers determined by both tests in the two groups of students were statistically similar during the test period. The RFFIT and the INH EIA gave comparable geometric mean titers, which differed significantly only on day 28 in the PVRV group. The effect of the new PVRV is comparable to that of the more expensive HDCV, as determined by the present test systems. The PVRV could therefore be the vaccine of choice, especially in tropical rabies-endemic areas, where the high cost of the HDCV has confined its use to a privileged few. PMID- 2203815 TI - Multivariate analyses of cellular carbohydrates and fatty acids of Candida albicans, Torulopsis glabrata, and Saccharomyces cerevisiae. AB - Quantitative data of major cellular carbohydrates distinguished Candida albicans or Torulopsis glabrata from Saccharomyces cerevisiae but not C. albicans from T. glabrata. Multivariate analyses of both carbohydrate and fatty acid variables (I. Brondz, I. Olsen, and M. Sjostrom, J. Clin. Microbiol. 27:2815-2819, 1989), however, differentiated all three species. PMID- 2203816 TI - Specificity of DNA probes for the detection of toxigenic Pasteurella multocida subsp. multocida strains. AB - Five DNA probes directed against different regions of the gene that encodes the dermonecrotic toxin of Pasteurella multocida subsp. multocida were examined for their ability to identify toxigenic P. multocida subsp. multocida strains. The specificities of the probes were studied with 96 strains of P. multocida subsp. multocida and 22 strains of 11 other bacterial species. Results of colony hybridization assays using these probes indicated that two of the five probes have potential diagnostic value. PMID- 2203817 TI - Comparison of the RIM-H rapid identification kit with conventional tests for the identification of Haemophilus spp. AB - A commercially available system, the RIM-H system (Austin Biological Laboratories, Austin, Tex.), was evaluated for its ability to rapidly and accurately identify various Haemophilus spp. A total of 110 clinical isolates were tested by both the RIM and conventional identification procedures. The RIM agreed with the standard identification for 100% of the Haemophilus influenzae (76 of 76) and 92.0% of the Haemophilus parainfluenzae (23 of 25) isolates tested. The identifications of Haemophilus parahaemolyticus, Haemophilus aphrophilus, and Haemophilus haemolyticus also correlated with those obtained by conventional methods. The RIM was found to be rapid and easy to use and was considered a suitable alternative to conventional identification procedures. PMID- 2203819 TI - A sonographic study of the morphology of the preterm neonatal hip. AB - Preterm and low-birth-weight infants are reported to have an increased risk of late presentation of congenital dislocation of the hip (CDH). A sequential sonographic study of hip morphology was made of 82 live preterm infants. Eighty two matched, term controls were scanned for comparison. The morphology of the hips was similar at birth. The increase in missed CDH cannot be explained in simple morphological terms. Abnormal birth sonograms resolved rapidly in the absence of clinical instability, casting doubt on the role of static sonographic appearances to predict the need for treatment in the immediate newborn period. PMID- 2203818 TI - Evaluation of a modified complement fixation test and an indirect hemagglutination test for the serodiagnosis of melioidosis in pigs. AB - A complement fixation test modified by the addition of porcine serum and an indirect hemagglutination test were used to detect antibodies to Pseudomonas pseudomallei in pigs. These tests together with cultural examinations were carried out with 250 pigs. The sensitivity and specificity values were 79.3 and 99.5% and 82.8 and 93.2% for the modified complement fixation and hemagglutination tests, respectively. When results from the combination of both tests were considered, the values were 86.2 and 92.8%, respectively. PMID- 2203820 TI - Acute osteomyelitis in children: a review of 116 cases. AB - We reviewed 116 cases of acute hematogenous osteomyelitis (AHO) (without septic joints) from 1979 to 1985 to establish current patterns of clinical presentation, modes of treatment, and success of therapy. We found that patients present early in the course of their disease, and many have no findings other than local tenderness and an elevated sedimentation rate. Sixty-four of the patients were treated nonoperatively. The average antibiotic treatment time was 2 weeks by intravenous (i.v.) administration followed by additional outpatient oral therapy for periods of up to 4 weeks. This treatment regimen applied specifically to acute osteomyelitis led to no known treatment failures. PMID- 2203821 TI - Enzymolysis of glomerular immune deposits in vivo with dextranase/protease ameliorates proteinuria, hematuria, and mesangial proliferation in murine experimental IgA nephropathy. AB - The therapeutic effects of saccharolytic and proteolytic enzymes were investigated in models of IgA nephropathy. Mesangial glomerulonephritis was induced in mice by intravenous injection of preformed soluble immune complexes of dextran sulfate and either IgA (J 558) or IgM (MOPC 104 E) anti-dextran MAb (passive model) or by immunization with DEAE dextran (active model). In the passive model, only 30-40% of dextranase-treated mice given IgA or IgM immune complexes had mesangial Ig or dextran deposits, compared with 100% of saline treated controls (P less than 0.01). There was no significant difference in mice given only protease. In the active model, dextranase and protease separately each reduced glomerular dextran and C3 deposits, and hematuria (P less than 0.01). Dextranase also reduced the glomerular IgA deposits (20 vs. 100% of saline treated mice) and the frequency and severity of mesangial matrix expansion (both P less than 0.02), but did not reduce the modest IgG or IgM codeposits. Protease reduced IgG and IgM deposits, proteinuria and mesangial hypercellularity compared with saline (P less than 0.02), but did not diminish IgA, and had no effect on mesangial matrix expansion. The combination of dextranase plus protease attenuated all components of glomerular injury as judged by clinical and pathological parameters, but inactivated dextranase plus inactivated protease had no effect on any parameter. We conclude that enzymatic digestion of antigen and antibody can reduce immune deposits, mesangial proliferation, proteinuria, and hematuria in experimental glomerulonephritis. PMID- 2203822 TI - Erythrocyte sequestration and anemia in severe falciparum malaria. Analysis of acute changes in venous hematocrit using a simple mathematical model. AB - Microvascular erythrocyte sequestration, the characteristic pathological feature of falciparum malaria, was evaluated using a mathematical model in 46 patients with severe infections. From admission radioisotopic circulating red cell volumes and simultaneous venous hematocrits, the model-derived sequestrum hematocrit (mean [95% confidence limits]: 0.70 [0.43-0.97], n = 29) was twice that of peripheral blood (0.33 [0.30-0.36]). Serial reticulocyte and radiolabeled erythrocyte counts indicated that small numbers of cells enter the circulation during initial therapy. The mean fall in hematocrit over 84 h in 26 nontransfused patients conformed to a three-term equation. A first-order decline (t1/2 2.0 h [0.6-3.4]) suggested an average 7.5% plasma volume expansion through rehydration. A zero-order 6.3% (3.1-9.5) fall (t1/2 25.7 h [21.2-30.2]) occurred contemporaneously with a fall in mean parasitemia from 4.5% (3.6-5.4); from these data the model-derived average sequestered erythrocyte volume (4.8% of the admission hematocrit) was similar to the peripheral parasite burden. A second, first-order fall (t1/2 1,047 h [278-1,816]) indicated loss of uninfected erythrocytes with mean lifespan 62 d. Predicted total plasma volume expansion during initial therapy (21.2%) was similar to radioisotopic estimates in 11 patients (17.3% [2.0-33.1]). Application of the model to individual patient data showed wide variations in relative proportions of circulating and sequestered parasitized cells. The model provides evidence of the nature and fate of all parasitized erythrocytes in malaria. PMID- 2203823 TI - Analysis of thymic endogenous retroviral expression in murine lupus. Genetic and immune studies. AB - Inbred mouse genomes contain two subclasses of proviruses related to mink cell focus-forming (MCF) retroviruses: polytropic (Pmv), and modified polytropic (Mpmv). To determine whether one of these subclasses is associated with murine lupus, oligonucleotide probes specific for Pmv or Mpmv sequences were used in Northern analyses. Thymus 8.4 kb Mpmv RNA was expressed in five of five lupus prone strains and crosses and this expression was not affected by genes that retard or accelerate development of lupus. Two of four leukemia-prone strains expressed low levels of such thymic transcripts, but none of 11 control strains did. 8.4 kb Mpmv RNA expression was not induced in thymuses of control mice by the lpr/lpr or gld/gld genotypes (which cause polyclonal immune activation) nor by treatment with mitogens. In contrast to Mpmv, thymic 8.4 kb Pmv expression was poorly associated with autoimmunity: it was easily detected in nearly all strains, and was increased by polyclonal activation in control mice. These studies indicate that the organ-specific thymic 8.4 kb Mpmv expression (a) is characteristic of several genetic backgrounds which predispose to murine lupus, (b) precedes and does not correlate with disease development, (c) is not due to polyclonal activation, and (d) is regulated independently of 8.4 kb Pmv expression. PMID- 2203824 TI - An immunoprotective molecule, the major secretory protein of Legionella pneumophila, is not a virulence factor in a guinea pig model of Legionnaires' disease. AB - We have examined whether a molecule that is capable of inducing immune protection, the major secretory protein (MSP) of Legionella pneumophila, is required for virulence in a guinea pig model of Legionnaires' disease. To do so, we have compared the virulence in guinea pigs of an isogenic pair of L. pneumophila, Philadelphia 1 strain, one of which produces MSP (MSP+) and one of which does not (MSP-). Both the MSP- strain and the MSP+ strain of L. pneumophila are highly virulent for guinea pigs, inducing similar signs and progression of illness. Both strains are lethal and have comparable LD50s and LD100s. Both strains multiply in the lungs of guinea pigs at a similar rate, and both strains produce indistinguishable pathological lesions in the lungs. Both strains maintain a stable phenotype with guinea pig passage, i.e., the MSP- strain does not regain the capacity to secrete MSP and the MSP+ strain retains its capacity to secrete MSP after lung passage. Although vaccination with MSP induces strong protective immunity in the guinea pig against lethal aerosol challenge with L. pneumophila, this protective immunogen is not required in its intact proteolytically active form for the expression of virulence by the intracellular pathogen L. pneumophila. This demonstrates that a protective immune response need not necessarily be directed against a virulence determinant and suggests that any molecule that allows the host immune system to detect and act against an intracellularly sequestered pathogen may potentially serve as a protective immunogen against such a pathogen. PMID- 2203825 TI - Vasoactive intestinal peptide in human nasal mucosa. AB - Vasoactive intestinal peptide (VIP), which is present with acetylcholine in parasympathetic nerve fibers, may have important regulatory functions in mucous membranes. The potential roles for VIP in human nasal mucosa were studied using an integrated approach. The VIP content of human nasal mucosa was determined to be 2.84 +/- 0.47 pmol/g wet weight (n = 8) by RIA. VIP-immunoreactive nerve fibers were found to be most concentrated in submucosal glands adjacent to serous and mucous cells. 125I-VIP binding sites were located on submucosal glands, epithelial cells, and arterioles. In short-term explant culture, VIP stimulated lactoferrin release from serous cells but did not stimulate [3H]glucosamine labeled respiratory glycoconjugate secretion. Methacholine was more potent than VIP, and methacholine stimulated both lactoferrin and respiratory glycoconjugate release. The addition of VIP plus methacholine to explants resulted in additive increases in lactoferrin release. Based upon the autoradiographic distribution of 125I-VIP binding sites and the effects on explants, VIP derived from parasympathetic nerve fibers may function in the regulation of serous cell secretion in human nasal mucosa. VIP may also participate in the regulation of vasomotor tone. PMID- 2203826 TI - Interleukin 1 inhibits insulin secretion from isolated rat pancreatic islets by a process that requires gene transcription and mRNA translation. AB - Recombinant human IL 1 beta inhibits glucose-induced insulin secretion from isolated pancreatic islets and from purified beta-cells obtained by fluorescence activated cell sorting (FACS) of dispersed islet cells. Brief (1 h) exposure of isolated islets to IL 1 produces sustained inhibition of insulin secretion for at least 17 h after the IL 1 has been removed from the culture medium. An inhibitory effect of IL 1 on insulin secretion is not observed when islets are coincubated with an inhibitor of DNA transcription (actinomycin D). This finding indicates that the inhibitory effect of IL 1 on insulin secretion requires transcription of one or more genes during the first hour of exposure of islets to IL 1. The inhibitory effect of IL 1 on insulin secretion also requires mRNA translation, because three structurally distinct inhibitors of protein synthesis (cycloheximide, anisomycin, and puromycin) prevent IL 1-induced inhibition of insulin secretion when added to islets after the 1-h exposure to IL 1. Two dimensional gel electrophoresis of islet proteins metabolically labeled with [35S]methionine demonstrates that IL 1 augments the expression of a 65-kD (pl approximately 6.5) protein by greater than 2.5-fold. These findings indicate that biochemical events occurring within 1 h of exposure of islets to IL 1 lead to an inhibition of insulin secretion that persists for at least 17 h after the removal of IL 1. One of the early biochemical effects of IL 1 on islets is gene transcription (0-1 h), which is followed by mRNA translation (after 1 h). Our results suggest that the inhibitory effect of IL 1 on insulin secretion is mediated by protein(s) whose synthesis is induced by IL 1. PMID- 2203827 TI - Cloning and characterization of a second complementary DNA for human tryptase. AB - A second cDNA for human tryptase, called beta-tryptase, was cloned from a mast cell cDNA library in lambda ZAP. Its nucleotide sequence and corresponding amino acid sequence were determined and compared with those of a previously cloned tryptase cDNA, now called alpha-tryptase. The 1,142-base sequence of beta tryptase encodes a 30-amino acid leader sequence of 3,089 D and a 245-amino acid catalytic region of 27,458 D. The amino acid sequence of beta-tryptase is 90% identical with that of alpha-tryptase, the first 20 amino acids of the catalytic portions being 100% identical. This identity, together with recognition of each recombinant protein by monoclonal antibodies directed against purified tryptase validate the tryptase identity of both alpha-tryptase and beta-tryptase cDNA molecules. Modest differences between the nucleic acid sequences of alpha- and beta-tryptase occurred throughout the cDNA molecules except in the 3' noncoding regions, which were identical. Although most highly conserved regions of amino acid sequence in the trypsin superfamily are conserved in both tryptase molecules, beta-tryptase has one carbohydrate binding site compared to two in alpha-tryptase, and one additional amino acid in the catalytic sequence. Regions of the substrate binding pocket in beta-tryptase (DSCQ, residues 218-221; SWG, residues 243-245) differ slightly from those in alpha-tryptase (DSCK, residues 217-220; SWD, residues 242-244). The presence of both alpha- and beta-tryptase sequences in each haploid genome was indicated by finding alpha- and beta tryptase specific fragments after amplification by PCR of genomic DNA in 10 unrelated individuals. Localization of both alpha- and beta-tryptase sequences to human chromosome 16 was then performed by analysis of DNA preparations from 25 human/hamster somatic hybrids by PCR. It is now possible to assess the expression of each tryptase cDNA by mast cells and the relationship of each gene product to the active enzyme. PMID- 2203829 TI - Tuberculosis in domesticated deer (Cervus elaphus): a large animal model for human tuberculosis. AB - Since the recent extensive domestication and farming of deer in New Zealand, tuberculosis (Tb) has presented a major health issue in farmed herds. The spectrum of disease pathology and immune reactivity in this naturally infected species represents a potentially valuable large animal model for the study of the underlying immunological and pathological mechanisms involved in Mycobacterium bovis infection and its spread. A combination of laboratory assays for the detection of tuberculosis in deer is described. Domesticated deer are genetically diverse and their exposure to natural variations in environmental conditions results in a spectrum of immune responses and pathology of Tb, similar to that found in man. The model has special relevance to the study of host responses to tuberculosis in immunocompromised individuals, particularly those in the third world. Elucidation of the mechanisms involved in immune responses to Tb in deer will facilitate the development of vaccines and improved diagnostic assays for Tb in man. PMID- 2203828 TI - Restricted expression of the erythroid/brain glucose transporter isoform to perivenous hepatocytes in rats. Modulation by glucose. AB - The "erythroid/brain" glucose transporter (GT) isoform is expressed only in a subset of hepatocytes, those forming the first row around the terminal hepatic venules, while the "liver" GT is expressed in all hepatocytes. After 3 d of starvation, a three- to fourfold elevation of expression of the erythroid/brain GT mRNA and protein is detected in the liver as a whole; this correlates with the expression of this GT in more hepatocytes, those forming the first three to four rows around the hepatic venules. Starvation-dependent expression of the erythroid/brain GT on the plasma membrane of these additional hepatocytes is lost within 3 h of glucose refeeding; however, by immunoblotting we show that the protein is still present. Its loss from the surface is possibly explained by internalization. PMID- 2203830 TI - Malignant, non-Hodgkin's lymphomas in Trypanosoma cruzi-infected rabbits treated with nitroarenes. AB - Use of 2-nitroimidazole, 5-nitrofuran and 5-nitroimidazole compounds in T. cruzi infected rabbits resulted in a reduction in duration of parasitaemia in comparison with untreated, infected rabbits. The chronic myocarditis associated with Chagas' disease was not, however, prevented in nitroarene-treated rabbits; lymphocytic infiltrates associated with cardiac cell lysis, in the absence of parasites in situ, were present in both treated and untreated rabbits. The carcinogenic effect of each trypanocidal nitroarene used in this study was also assessed. Administration of nitroarenes to rabbits resulted in the appearance of solid tumours in 37.8 per cent of animals that received drug therapy. Untreated, control rabbits in this series did not show tumour growth. Furthermore, malignant, mixed-cell type, non-Hodgkin's lymphomas were seen in 32.4 per cent of the treated rabbits. It seems that a direct relationship could be present between the presence of the nitro group, the trypanocidal cytotoxicity and the prevalence of tumours. Benznidazole cleared up parasitaemias in the shortest time and was associated with 41.6 per cent of lymphoma growths, whereas MK-436 required twice as much time to clear blood parasites, and showed lymphomas in 25 per cent of experimental rabbits. The demonstration of a high prevalence of malignant tumours in addition to the chronic myocarditis of Chagas' disease in nitroarene-treated rabbits is important since indiscriminate use of such compounds currently used to treat T. cruzi infections in man could increase the risk of lymphoma. PMID- 2203831 TI - Lymphomatoid granulomatosis of eyelid and brow with progression to lymphoma. AB - Lymphomatoid granulomatosis is an uncommon lymphoreticular disease that primarily involves the lungs, skin, and central nervous system and has a high mortality rate. This is the first report in the American literature of lymphomatoid granulomatosis with involvement of the skin of the eyelid and brow. After a protracted clinical course, the patient died of pulmonary complications. PMID- 2203832 TI - Cutaneous leishmaniasis in Texas: report of a case and review of the literature. AB - Cutaneous leishmaniasis is endemic in south central Texas. There have been at least eight cases, four of which have been reported since 1980. An additional case of cutaneous leishmaniasis is reported in a 56-year-old woman from Sandia, Texas. The diagnosis was confirmed by culture of Leishmania mexicana var. mexicana. PMID- 2203833 TI - Case report and review of resolved fusariosis. AB - Erythematous macules, nonpalpable and palpable purpura, and flaccid pustules developed in a 59-year-old man with acute lymphocytic leukemia 8 days after reinduction chemotherapy with cytosine arabinoside and daunorubicin. Tissue and blood cultures grew Fusarium proliferatum, and a skin biopsy specimen revealed fungal vasculitis. Anemia and muscle weakness accompanied the disseminated infection, for which the patient received granulocyte transfusions and amphotericin B, ketoconazole, rifampin, and griseofulvin. Skin lesions and fungemia resolved with recovery of the bone marrow, and 51 days after the completion of his chemotherapy he returned home. If promptly recognized and aggressively treated, disseminated fusariosis is responsive to therapy. Infection with Fusarium species should be suspected in profoundly neutropenic patients in whom disseminated palpable purpura and myositis develop concomitantly. PMID- 2203834 TI - Immunocompetent cells and epithelial cell modifications in molluscum contagiosum. AB - We studied lesions of molluscum contagiosum with a panel of monoclonal antibodies to determine the phenotype of infiltrating cells and antigen modifications of infected keratinocytes. Our data indicate (1) a complete lack of immunocompetent cells in the viral lesions, and simultaneously a loss of B2-microglobulin reactivity by molluscum bodies, a cellular activation of EGF and transferrin receptors and expression of CD36 antigen of these bodies; (2) a moderate infiltrate of activated T cells and monocytes in the underlying epidermis; (3) an increase of Langerhans cell density and a CD36 expression by the surface of upper layer keratinocytes in the perilesional epidermis. PMID- 2203835 TI - [Sodium hypochlorite in endodontics]. AB - Sodium hypochlorite is still today the most popular irrigating solution used in endodontics. History, chemical and bactericidal properties, effect on periapical tissue, dissolution of pulp tissue, removal of debris and depth of penetration and attempts to improve its activity are discussed in this article. PMID- 2203836 TI - [The butterfly bridge: causes of debonding, 18 years clinical observation]. AB - For 18 years, the acid-etched bridge has been put to good use. Clinical observations over this period of time allow us to take a step back and review this conservative technique. Using the results of clinical research, this article aims to evaluate the performance and basic principles relative to the acid-etched bridge. The primary and secondary causes of debonding are also identified. PMID- 2203837 TI - Samuel J. Stegman, M.D. 1939-1990. In memoriam. PMID- 2203838 TI - ASDS 20th anniversary: academic dermatologic surgery: a short review. PMID- 2203839 TI - The literature of dermatologic surgery and oncology: 1970--present. PMID- 2203840 TI - The role of the family in relation to chronic pain: review of the literature. AB - As families maintain the primary responsibility for the care of the chronic pain sufferer, this paper examines the family's aetiological role in chronic pain, the ways in which the family influences and maintains pain, and the impact that chronic pain has on the family unit. Although some of the research is contentious, it can be concluded that, (a) there is a tendency for patients to come from families which include another member suffering from pain or illness, (b) that it is conceivable that spouses reinforce pain behaviors in their partners, and (c) that it is possible that the chronic pain sufferer may significantly subscribe to poor marital relationships, poor sexual adjustment and high levels of emotional distress. PMID- 2203841 TI - A contribution of qualitative research to a better understanding of diabetic patients. AB - In spite of advances in the management of diabetes mellitus, late complications still present problems. Research suggests that improved metabolic control, including the change of lifestyle, which requires the patient's own willingness and ability to adapt, could limit those complications. This article is intended to provide the background to a long-term research programme designed to gain a deeper understanding of diabetic patients' perspectives in their attempt to adapt. It describes an important phase in the programme, building on the conceptual categories emerging from a group of diabetic patients in a previous study (Ternulf Nyhlin et al. 1987). It also uses the experiences of further groups of diabetic patients, in an attempt to show the usefulness of a cumulative approach towards the building up of a theoretical framework. Some inherent methodological issues are discussed. PMID- 2203842 TI - Literature review on the images of the nurse and nursing in the media. AB - This study concentrates on the images of the nurse and nursing seen most commonly in the media and attempts to trace the images back to their origins and to explain their continued use, despite the rapidly changing role of the nurse in today's world. The images have been derived mostly from the historical roots of nursing and sometimes as a reaction to the increasing influence of the feminist movement. The author takes a look at the four main images of the nurse seen in the media, which are the ministering angel, the battleaxe, the naughty nurse and the doctor's handmaiden and then goes on to take a brief look at the other images commonly perpetuated by the media. The author summarizes the probable effects of the media stereotypes on nurses themselves and the service they provide and also takes a look at attempts to dispel these stereotypes. PMID- 2203843 TI - Medicare and optometry. PMID- 2203844 TI - Programmed cell death: new thoughts and relevance to aging. AB - Cell death is a common phenomenon in developmental biology, and recent data suggest that it is as tightly regulated as mitosis. For numerous systems endocrine and neuronal factors are required to maintain viability of cells, as are specific diffusible and other unknown factors deriving from intimate cell-to cell contact; and, in some instances, specific hormones or other circulating factors induce spontaneous self-destruction by the targeted cells. Some cells such as thymocytes may be primed to self-destruct and hence activate specific enzymes. In others, the doomed cell up-regulates a limited number of genes just before it dies. Of these genes, several are known but are not considered to cause cell death; others are under investigation. Although the situation is clearest for developmental biology, it appears that the presumptively random loss of cells in senescence results from invocation of the same mechanisms. Understanding and control of these mechanisms could conceivably lead either to protection against cell loss or specific induction of lysis in malignant cells. PMID- 2203845 TI - Effects of age and adenosine in the modulation of insulin action on rat adipocyte metabolism. AB - The age-related declines in the antilipolytic and lipogenic actions of insulin were studied in adipocytes from rats aged 2, 6, 12, and 24 months. Since adenosine modulates insulin action, its concentration was controlled by treatment of adipocytes with adenosine deaminase and addition of the non-metabolizable adenosine analog, N6-[(R)-(-)1-methyl-2-phenethyl] adenosine (PIA). Inhibition of isoproterenol-stimulated lipolysis by PIA increased significantly by 6 months of age. Decreasing the concentration of PIA rendered the adipocytes from the 6-, 12 , and 24-mo-old rats less sensitive to the antilipolytic effect of insulin. Basal and insulin-stimulated lipogenesis decreased with aging. PIA increased insulin stimulated lipogenesis at 0.2 ng/ml insulin only in the 2-month-old rats. PIA reduced insulin-stimulated lipogenesis at higher insulin doses in the oldest rats. These results suggest that aging causes quantitative declines in maximal lipolysis and basal and maximal lipogenesis. Maturation may cause a decline in sensitivity to insulin, but adenosine in sufficient concentration reverses the acquired resistance to the antilipolytic effect of insulin. PMID- 2203846 TI - Glucocorticoid-induced osteoporosis: mechanisms for bone loss; evaluation of strategies for prevention. AB - Osteoporosis is a common complication of chronic glucocorticoid therapy, especially in older patients who already are at risk of having a reduced bone mass. Glucocorticoids cause bone loss by altering the bone remodeling sequence: bone resorption by osteoclasts is increased, and bone formation by osteoblasts is decreased. Serum levels of osteocalcin, a protein made by osteoblasts, are decreased with glucocorticoid therapy, further evidence of decreased osteoblast function. Glucocorticoids decrease calcium absorption by the gastrointestinal tract and increase renal calcium excretion. Several recent studies suggest that low-dose glucocorticoid therapy is not associated with bone loss. Calcium supplementation with vitamin D is recommended. Several short-term studies have shown prevention of glucocorticoid-induced bone loss with bisphosphonates, calcitonin, and progesterone. Long-term clinical trials should be undertaken to determine strategies to prevent this type of osteoporosis. PMID- 2203847 TI - Calcium supplementation lowers serum parathyroid hormone levels in elderly subjects. AB - To determine the effect of calcium supplementation on parathyroid hormone levels (PTH) in a group of elderly subjects at risk for developing Type II (senile) osteoporosis, 40 healthy volunteers participated in a randomized double-blind crossover study. Calcium carbonate or placebo was administered for 4 weeks, followed by a 4-week administration of the alternative intervention. Fasting blood samples and 24-hour urine collections were obtained at baseline, and at the end of each intervention period. Calcium supplementation (1000 mg/day) decreased serum PTH levels from a mean of 50.1 +/- 3.0 pg/ml to 41.9 +/- 2.4 pg/ml (p less than .001). Additionally, urine calcium excretion significantly increased during calcium administration (from 3.64 mmol/mmol creatinine at baseline to 4.28 mmol/mmol creatinine), but creatinine clearances and serum calcium levels remained unchanged. Type II osteoporosis has been associated with age-related increases in PTH levels. We have demonstrated the ability of increased calcium intake to decrease these levels, which may have implications for the management of a subset of patients with involutional osteoporosis. PMID- 2203849 TI - 2450 MHz oesophagus applicator with multi-temperature sensors and its temperature control equipment. AB - A 2450 MHz microwave applicator for heating the oesophagus, complete with temperature monitoring and controlling equipment, is described. The geometrical parameters and performance in both animal experiments and clinical applications are discussed. PMID- 2203848 TI - Multi-institutional clinical studies on hyperthermia combined with radiotherapy or chemotherapy in advanced cancer of deep-seated organs. AB - Multi-institutional studies on clinical hyperthermia of deep-seated tumours were undertaken using 8 MHz radiofrequency capacitive heating devices (Thermotron RF 8) at seven institutions. Each institute was designated to treat specific organs. This paper contains the accumulations of the results obtained at different institutions charged for different tumours. Deep-seated tumours in the lung, stomach, pancreas, liver, urinary bladder and rectum were treated. A total of 177 cases examined from January 1985 to December 1988 included 96 cases (54%) treated with radiotherapy plus hyperthermia, among which 14 cases were pre-operative. Of 177 cases, 81 (46%) were treated with chemotherapy plus hyperthermia. Complete response (CR) and partial response (PR) were obtained in 80% of the cases with lung cancer, 39% with stomach cancer, 56% with liver cancer, 35% with pancreas cancer, 71% with urinary bladder cancer, 100% with primary rectal cancer, and 47% with recurrent rectal cancer. Thermometry was performed using two techniques; one is direct measurement of intratumour temperature in lung and liver cancers, the other is indirect measurement of intracavitary temperature for stomach, pancreas, urinary bladder and rectal cancers. Intratumour temperatures were measured in 30 of the 43 tumours of the lung and liver. The maximum tumour temperature was greater than 42 degrees C in 23 (77%) of the 30 tumours. Intracavitary temperatures were measured in 133 (99%) of the 134 tumours of stomach, pancreas, urinary bladder and rectum. An intracavitary temperature greater than 42 degrees C was obtained in 98 (73.7%) of the 133 tumours. The contribution of hyperthermia in improving the quality of life of patients under terminal care was also investigated. It was indicated that hyperthermia was one of the most effective treatment techniques for advanced or inoperable cases. In this study local control rate (LCR) was mainly discussed because the period of follow-up was only 3 years. Side-effects were observed in 37 cases (21%); main side-effects were fatty induration, pain during treatment and burn. However, no side-effects were severe enough to interrupt therapy. PMID- 2203850 TI - Kainic acid and formoguanamine effects on environmentally-induced eye lesions in chicks. AB - Several neurotoxins are known which destroy some specific retinal component or other link in the visual pathway. We have employed such reagents to induce blindness in chicks, in order to explore the role of vision in the development of light-induced avian glaucoma (LIAG) and/or lid-suture myopia (LSM). Chicks made pharmacologically blind with formoguanamine failed to develop LSM. Under LIAG conditions, increased eye weight and global enlargement did not occur, but the characteristic anterior segment changes were seen. Thus LIAG globe enlargement, and LSM axial lengthening, appear to be vision-driven, but anterior segment changes are probably separately controlled. The retinal neurotoxin kainic acid rendered chicks behaviorally blind in the eye into which it was injected intravitrially, but this failed to prevent LIAG changes in either anterior segment or growth of the globe. Chicks reared under LSM conditions, and treated with kainic acid were not different from untreated controls, in that they developed globe enlargement in spite of their pharmacologically-induced blindness. Preliminary trials with quisqualic acid, another retinal neurotoxin, indicate that this agent, like kainic acid, cannot prevent LIAG eye enlargement. Several quis-treated eyes developed phthisis bulbi however, and thus could not be included among those assessed for eye weight and dimensional measurements. PMID- 2203851 TI - New directions in the optimization of ocular drug delivery. AB - The main effort in ocular drug delivery during the past two decades has been on the design of systems to prolong the residence time of topically applied drugs in the conjunctival sac. Four recent developments promise to chart a new course in ocular drug delivery research: collagen shield as a topical ocular drug delivery system, in-situ activated gel-forming systems, noncorneal route of ocular drug penetration, and need for minimizing the systemic absorption of topically applied drugs. PMID- 2203852 TI - Intraocular pressure lowering effects of the renin inhibitor ABBOTT-64662 diacetate in animals. AB - Corneal application of enalkiren (ABBOTT-64662), [N-(3-amino-3-methyl-1- oxobutyl)-4-methoxy-L-phenylalanyl]-N-[1S,2R,3S)-1-(cyclohexylmethyl+ ++)-2,3- dihydroxy-5-methylhexyl]-L-histidinamide], a renin inhibitor compound, lowered intraocular pressure (IOP) in unanesthetized rabbits and anesthetized monkeys. IOP was significantly decreased for at least 60 minutes after administration of a 0.3% solution of enalkiren in monkeys and for at least 90 minutes after the administration of 0.1% and 0.3% solutions in rabbits. Enalkiren did not affect systemic blood pressure or heart rate in anesthetized monkeys after topical application to the cornea. The IOP lowering activity of enalkiren suggests a potential functional role for the renin angiotensin system in the modulation of IOP. PMID- 2203853 TI - Detection of bacterial endotoxins: another step forward. PMID- 2203854 TI - Optimization of detection of bacterial endotoxin in plasma with the Limulus test. AB - Detection and quantification of bacterial endotoxin in plasma by the Limulus amebocyte lysate test (or other assays for endotoxins) is hindered by the presence of inhibitors. Treatment of plasma to overcome inhibitory activities is required before plasma can be successfully assayed for endotoxin. We have conducted an investigation comparing the three most commonly used procedures (dilution-heating, trifluoroacetic acid oxidation, and chloroform extraction) for treatment of plasma before its assay for endotoxin with the chromogenic Limulus test. Initially, conditions were optimized for treatment of plasma by each of these methods. Subsequently, a direct comparison of the three plasma treatment procedures was performed with plasma spiked with known concentrations of endotoxin. The optimized dilution-heating procedure resulted in the most sensitive detection of endotoxin, with sensitivity approximately 10 times greater than the optimized trifluoroacetic acid oxidation procedure and approximately 100 times greater than treatment of plasma by chloroform extraction. Maximal detection of low concentrations of endotoxin by the chromogenic Limulus test was obtained by dilution of plasma fourfold with 0.15 mol/L NaCl followed by heating at 60 degrees C for 30 minutes. This procedure was simple, rapid, and did not involve addition of any reagents to plasma that could potentially add contaminating endotoxin. PMID- 2203855 TI - Dietary fish oil intake: effects on glomerular prostanoid formation, hemodynamics, and proteinuria in nephrotoxic serum nephritis. AB - Dietary fish oil intake improves glomerular pathology and proteinuria in murine models of autoimmune disease. We evaluated glomerular prostanoid formation, glomerular hemodynamics, and proteinuria in rats with nephrotoxic serum nephritis (NSN) to test whether this beneficial effect of marine lipids also applies to other animal models of glomerular immune injury. Rats were fed diets (8 weeks) containing either cod liver oil or sunflower oil. NSN was induced with a rabbit anti-rat glomerular basement membrane antiserum. Antibody injection significantly stimulated glomerular thromboxane B2 (TxB2) formation in animals fed cod liver oil and sunflower oil at 2 hours, 24 hours, and 7 days. TxB2 production in glomeruli of sunflower oil rats, however, was five to seven times higher when compared with that in rats fed cod liver oil. The dietary regimen led to a significant decrease of glomerular TxB2 and prostaglandin E2 formation in the animals receiving cod liver oil when compared with those fed sunflower oil. Induction of NSN resulted in a significant fall of inulin clearance (Cin) and paraaminohippurate clearance at 2 hours, 24 hours, and 7 days in both groups. The decrease in Cin at 2 hours was greater in rats fed cod liver oil when compared with animals receiving sunflower oil (p less than 0.02); it was not different, however, at 24 hours and 7 days. Animals with NSN developed proteinuria. There was no difference in protein excretion between rats fed cod liver oil or those fed sunflower oil (days 2 and 7).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203856 TI - Part I. Painting background. Part II. Primary aldosteronism, a new clinical syndrome, 1954. PMID- 2203857 TI - The gift of insulin. PMID- 2203858 TI - The clinical laboratory and the mental hospital at the turn of the century. PMID- 2203860 TI - Report from the Consensus Conference on the Validation of Chiropractic Methods. PMID- 2203859 TI - Interactions between epithelial cells and T lymphocytes: role of adhesion molecules. AB - Cell-cell interaction is critical for normal T cell development and function. A number of adhesion molecules important in T cell interactions with other cell types have been defined. This paper reviews the role of two adhesion pathways, CD2/LFA-3 and LFA-1/ICAM-1, in T cell interactions with epithelial cells of the thymus and skin. While thymic epithelium-T cell interactions are mediated by both the LFA-1/ICAM-1 pathway and the CD2/LFA-3 pathway, epidermal-T cell interactions are mediated primarily by the LFA-1/ICAM-1 pathway. Although ICAM-1 is not expressed in vivo on epidermal keratinocytes in normal skin, ICAM-1 is expressed by epidermal keratinocytes at the site of T cell infiltration in inflammatory dermatitis. ICAM-1 is expressed in vivo on thymic epithelium. These antigen independent adhesion molecules play an important role in the cell-cell interactions associated with T cell differentiation and function. PMID- 2203861 TI - Addressing the issue of cataloging and making accessible chiropractic literature: Part II. Pilot software development program. AB - Health science journals are a principle source of new knowledge for chiropractors, chiropractic faculty, and students. Regrettably, clinically or educationally relevant articles (appearing in the nearly 20,000 journals annually) are often overlooked due to access difficulties. Innovations are needed to assist the reader to select articles relevant to chiropractic and reduce the time spent sorting through the volumes of literature. A solution to those problems of accessing, obtaining, and storing article citations from the chiropractic literature come from a pilot computerized program developed for use on the Los Angeles College of Chiropractic (LACC) campus. The Chiropractic Literature Archive and Search Program (CLASP) is dedicated to chiropractic literature. It provides rapid access to the literature and directs the user to one of the participating chiropractic campuses where the article can be found. Because of its ease of operation, the program is a useful tool for nearly all areas of chiropractic, ranging from education and research to clinical patient management. The program would be inexpensive to fully implement, and the hardware needed is minimal. Important protocols have been developed for database input, use and maintenance. Testing of this program on the LACC campus reveals that such a program is capable of making citations of the chiropractic literature available within days of their publication. PMID- 2203862 TI - Myositis ossificans. AB - Myositis ossificans is a fairly common disorder that typically involves progressive heterotropic bone formation. A typical case is discussed in this paper. The radiographic findings in myositis ossificans are relevant in differentiating it from a malignant bone tumor and a benign process. Myositis ossificans can cause impairment to a joint with poor rehabilitative results. Limitation of joint function and little reabsorption of the heterotopic bone formation is common. Most cases are posttraumatically related with the brachialis and the quadricep femoris muscles frequently involved. This is especially true for sport injuries. PMID- 2203863 TI - The birth of the medical humanities and the rebirth of the philosophy of medicine: the vision of Edmund D. Pellegrino. PMID- 2203864 TI - Edmund D. Pellegrino: a biographical note. PMID- 2203865 TI - Establishing the moral basis of medicine: Edmund D. Pellegrino's philosophy of medicine. AB - Edmund D. Pellegrino's philosophy of medicine is explored in categories such as the motivation in constructing a philosophy of medicine, the method, the starting point of the doctor-patient relationship, negotiation about values in this relationship, the goal of the relationship, the moral basis of medicine, and additional concerns in the relationship (concerns such as gatekeeping, philosophical anthropology, axiology, philosophy of the body, and the general disjunction between science and morals). A critique of this philosophy is presented in the following areas: methodology, relation to ontology and sociology, the dynamic of individual and social concerns, and the new social condition of medicine. Finally, some suggestions for the future revitalization of philosophy of medicine are made based on Pellegrino's ideas. The focus throughout is on the moral basis and moral consequences of the philosophy of medicine, and not on other important themes. PMID- 2203866 TI - Justice in health care: the contribution of Edmund Pellegrino. AB - Edmund Pellegrino has pioneered work in medical ethics calling for a reconstruction of Hippocratic ethics. In particular, he has spoken of incorporating principles that concern justice and the common good. This article traces his commitment to the common good, concern for the poor, opposition to libertarianism, acknowledgement of the necessity of rationing, and reluctance to give clinicians social allocational tasks. It asks how Pellegrino relates distributive justice to the common good. Drawing on his theory relating autonomy to patient-centered beneficence (in which autonomy is one element of the good rather than a side constraint on the good), the author argues that Pellegrino appears to make justice one element of the common good rather than a distributional moral constraint on promoting the good. He suggests that Pellegrino stands in three consequentialist or teleological moral traditions: professional physician ethics, Aristotelianism, and Catholic moral theology, but that there are the makings of a more independent, more egalitarian theory of justice in his writings. PMID- 2203867 TI - Humanities in medical education: some contributions. AB - The author discusses the contribution of humanities teaching in medical education. Five "qualities of mind" specifically engendered by the humanistic disciplines are isolated, delineated, and illustrated: critical abilities, flexibility of perspective, nondogmatism, discernment of values, and empathy and self-knowledge. PMID- 2203869 TI - Ars medicina et conditio humana. Edmund D. Pellegrino, M.D., on his 70th birthday. AB - In his writings, Edmund Pellegrino analyzes four deficiencies in the humanity of those who fall ill: the loss of (1) freedom of action, (2) freedom to make rational choices, (3) freedom from the power of others, and (4) a sense of the integrity of the self. Since Pellegrino's analysis and commitment to virtue-based ethics preceded much of the attention later given by philosophers to the importance of the moral principle of autonomy (in contrast to beneficence) in patient care, it is helpful to trace the source of his commitment to virtue-based ethics and his account of freedom to Aristotle's analysis of the human soul, as an entelechy of an intact and healthy living organism that, unimpeded by illness, moves itself to act, to actualize its intellectual potential in the form of making rational choices, and to free itself from the power of others by remaining independent and without need of continuous assistance, while at the same time retaining the integrity of a unified self that can act, think, and choose for itself autonomously. PMID- 2203868 TI - Medicine and dialogue. AB - Physicians have for some time been questioning the prevailing view of medicine as applied biology. It is urged that medicine needs to be reconceived so as to provide appropriate emphasis on the patient's experience and understanding of illness. After reviewing these arguments and the scientific paradigm underlying the received view in light of certain themes in medicine's history and of current thinking, Pellegrino's thesis is analyzed: medicine should be understood as an inherently moral enterprise, a form of praxis focused on "the healing relationship". Understanding the illness experience and the professed healer's "compassion" supports Pellegrino's view, and suggests that the healing relationship is perhaps best conceived as a form of dialogue. PMID- 2203870 TI - Randomized controlled trial of Cassia alata Linn. for constipation. AB - Cassia alata Linn. is a medical plant. Its leaves have been claimed to be effective as a laxative. The studies done so far have shown no toxicity as a result of consuming Cassia alata Linn. leaves. The plant has been found to contain anthraquinones, presumed to be the active ingredient causing the laxative effect. The objective of the study was to test efficacy of Cassia alata Linn. leaves for treatment of constipation compared with a placebo and mist. alba in a multicenter randomized controlled trial carried out in one provincial and 5 community hospitals. Eighty adult patients admitted to 5 community hospitals and one provincial hospital with at least 72 hours of constipation were included in the study. Twenty-eight patients were in the placebo group, 28 in the mist. alba group, and 24 in Cassia alata Linn. group. Each patient was given 120 ml of fluid with caramel color, mist. alba, or Cassia alata Linn. infusion at bed time. Evaluation was performed after 24 hours whether the patient defecated or not. The characteristics of the patients among the three groups were not different. Eighteen per cent of patients in the placebo group passed stools within 24 hours, whereas, 86 and 83 per cent of patients in mist. alba and Cassia alata Linn. groups respectively, passed stools. The differences observed between placebo and mist. alba, placebo and Cassia alata Linn. were statistically highly significant, P less than 0.001 and clinically important. Minimal self-limited side effects, i.e., nausea, dyspepsia, abdominal pain and diarrhea were noted in 16-25 per cent of the patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203871 TI - Malaria parasitization and hormonal imbalance in virgin mice. AB - The effect of the malaria parasite plasmodium berghei berghei on the estrus cycle was studied in rodents. It was observed that there was a delay at the proestrus phase of the estrus cycle. Endocrinological evidence for lack of ovulation at estrus during infection was presented. Although there was an elevation in the level of immune complexes and white blood cell counts, the red blood cell counts decreased as infection progressed. Anal temperature recordings showed pyrexia. There was a wide difference in the mating success of the control group when compared to the experimental group. PMID- 2203873 TI - The captopril test for identification of renovascular hypertension: value and immediate adverse effects. AB - To develop a screening test for identification of renovascular hypertension, the blood pressure and plasma renin concentration responses to an oral test dose of captopril (6.25 mg) were studied in 47 hypertensive patients of mean age 61 years (range 34-85 years). Blood pressure was measured at 15-min intervals for 90 min after administration of captopril. Blood samples for plasma renin determination were drawn immediately before and 90 min after drug administration. Eleven patients had renal artery stenosis. The fall in diastolic blood pressure in these patients was greater, on average, than in patients with other forms of hypertension (30 mmHg vs. 14 mmHg, P less than 0.01), as was the increase in plasma renin concentration (188 mU l-1 vs. 2 mU l-1, P less than 0.01). This study demonstrates that the short-term captopril test is useful for distinguishing patients with renovascular disease from those with other forms of hypertension. During the test, 7 patients (15%) exhibited reversible cerebral symptoms. In two of these subjects digital subtraction angiography was performed, which revealed stenosis of the carotid artery. Consequently, it is suggested that captopril should not be used in patients with arteriosclerotic stenoses of the carotids. PMID- 2203872 TI - Mortality and morbidity during one year of follow-up in suspected acute myocardial infarction in relation to early diagnosis: experiences from the MIAMI trial. AB - From a large randomized multicentre trial of metoprolol in suspected acute myocardial infarction (n = 5778) we report on the outcome during 1 year of follow up, in relation to early diagnosis. Patients who developed a confirmed infarction had a 1-year mortality rate of 12.8%. This was significantly higher than the mortality rate of 6.3% (P less than 0.001) in patients with possible infarction and it was also higher than that in patients with no infarction, which was 5.0% (P less than 0.001). A multivariate analysis showed that independent risk predictors in the clinical history of patients without confirmed infarction were a history of angina pectoris, chronic use of digitalis and advanced age. After 1 year, angina pectoris was most common in patients with an initial possible infarction. These patients were also in most urgent need of bypass surgery. We thus conclude that the mortality during 1 year of follow-up among patients with an initially strongly suspected acute myocardial infarction was clearly related to whether or not the patient developed a myocardial infarction. PMID- 2203874 TI - Treatment of hyperglycaemia in the elderly with diabetes mellitus. PMID- 2203875 TI - The predictive capability of the glycaemic response to spaghetti in non-insulin dependent (NIDDM) and insulin dependent (IDDM) diabetic subjects. AB - To evaluate the predictive capability of the postprandial blood glucose response after consumption of a starch-rich meal, we compared the glycaemic effects of spaghetti (60 g) taken alone and with bolognese sauce (167 g). The study was carried out in both NIDDM (n = 6) and IDDM (n = 6) subjects. The latter had achieved normoglycaemia 120 min prior to the test meal by means of an artificial pancreas (Biostator) which provided constant insulinaemia during the observation period of 4 h. We found that the areas of blood glucose (above basal) were identical irrespective of whether spaghetti was taken alone or as part of a mixed meal in both NIDDM (484 +/- 154 mmol l-1 240 min-1 vs. 393 +/- 126 mmol l-1 240 min-1) and IDDM subjects (610 +/- 143 mmol l-1 240 min-1 vs. 770 +/- 135 mmol l-1 240 min-1). The insulin levels were identical in the IDDM diabetics. By contrast, the mixed meal caused a more marked insulinaemic response than spaghetti per se in the NIDDM subjects (3187 +/- 637 mU l-1 240 min-1 vs. 1940 +/- 235 mU l-1 240 min-1; P less than 0.05). In conclusion, the predictive capability of the glycaemic response to spaghetti was good in both IDDM and NIDDM diabetic subjects, at least under the conditions of the present study. PMID- 2203876 TI - Avian vasculogenesis and the distribution of collagens I, IV, laminin, and fibronectin in the heart primordia. AB - The heart-forming regions of the early embryo are composed of splanchnic mesoderm, endoderm, and the associated ECM. The ECM of the heart-forming regions in stage 7-9 chicken embryos was examined using immunofluorescence. Affinity purified antibodies to chicken collagens type I and IV, chicken fibronectin, and mouse laminin were used as probes. We report that (1) the basement membrane of the endoderm contains immunoreactive laminin and collagen IV; (2) the nascent basement membrane of the heart splanchnic mesoderm contains immunoreactive laminin, but not type IV collagen, and (3) the prominent ECM between the splanchnic mesoderm and the endoderm (the primitive-heart ECM) contains collagen IV, collagen I, fibronectin, but not laminin. In addition, we describe microscopic observations on the spatial relationship of cardiogenic cells to the primitive-heart ECM and the endodermal basement membrane. PMID- 2203877 TI - Fate mapping the avian epiblast with focal injections of a fluorescent histochemical marker: ectodermal derivatives. AB - A microinjection technique is described for fate mapping the epiblast of avian embryos. It consists of injecting the epiblast of cultured blastoderms with a fluorescent-histochemical marker, examining rhodamine fluorescence at the time of injection in living blastoderms, and assaying for horseradish peroxidase activity in histological sections obtained from the same embryos collected 24 h postinjection. Our results demonstrate that this procedure routinely marks cells, allowing their fates to be determined and prospective fate maps to be constructed. Two such maps are presented for ectodermal derivatives of the epiblast: one for late stages of Hensen's node progression (stages 3c through 4) and one for early stages of node regression (stages 4 + through 5). These new maps have six significant features. First, they show that regardless of whether the node is progressing or regressing, the flat neural plate extends at least 300 microns cranial to, 300 microns bilateral to and 1 mm caudal to the center of Hensen's node. Second, they confirm our previous fate mapping studies based on quail/chick chimeras. Namely, they show that the prenodal midline region of the epiblast forms the floor of the forebrain and the ventrolateral part of the optic vesicles as well as MHP cells (i.e., mainly wedge-shaped neurepithelial cells contained within the median hinge point of the bending neural plate); in contrast, paranodal and postnodal regions contribute L cells (i.e., mainly spindle-shaped neurepithelial cells constituting the lateral aspects of the neural plate). Third, they reveal a second source of MHP cells, Hensen's node, verifying previous studies of others based on tritiated thymidine labeling. Fourth, they demonstrate, in contrast to studies of other based on vital staining, carbon marking, and chorioallantoic grafting but in accordance with our previous studies based on quail/chick chimeras, that the cells contributing to the four craniocaudal subdivisions of the neural tube (i.e., forebrain, midbrain, hindbrain, and spinal cord) are not yet spatially segregated from one another at the flat neural plate stage, although more cranial neural plate cells tend to form more cranial subdivision and more caudal cells tend to form more caudal subdivisions. Thus, single injections routinely mark multiple neural tube subdivisions. Probable reasons for the discrepancy between our present results and the previous results of others is discussed. Fifth, they suggest that cells contributing to the surface ectoderm and neural plate are not yet completely spatially segregated from one another at the flat neural plate stage, particularly in caudal postnodal regions. Sixth, they delineate the locations of the otic placodes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2203878 TI - The neural basis of the deficit syndrome of schizophrenia. AB - The deficit syndrome is a domain of schizophrenic psychopathology defined by the presence of primary negative symptoms that are enduring features of a patient's function between periods of relapse. Lesions of the putative neural circuit underlying social affiliation and social behavioral cues in nonhuman primates and other mammals cause behavioral impairments in animals that model the diminished social drive, poverty of speech, and blunted affect of the deficit syndrome. Components of this circuit include the amygdala, periamygdalar cortex, and part of the prefrontal cortex. Abnormal function of this functional circuit may underlie the deficit syndrome. PMID- 2203879 TI - Some biological and behavioral features associated with clinical personality types. AB - The author reviews supporting evidence for the existence of two personality prototypes that correspond to two DSM-III-R personality "clusters." These hypothetical personality prototypes are characterized by extreme variations along several interrelated personality trait dimensions and by differences in two biological measures. The possibility that individual differences in central serotonin and/or catecholamine activity may underlie some of the features associated with these prototypes is discussed in light of current data. The usefulness of this conceptualization as a supplemental axis of personality classification is suggested. PMID- 2203880 TI - Stereochemical and biochemical aspects of some organoboron complexes of sulphur donor ligands. AB - Synthetic, structural and biochemical aspects of some organoboron complexes of sulphur containing ligands having ONS and SNNS donor systems have been described. The ligands were prepared by the condensation of 1-phenyl-1,3-butanedione, 2,4 pentanedione, diphenylethanedione, 2,3-butanedione, ethanedial and 1,4 benzenedialdehyde with 2-mercaptoaniline. The unimolar reactions between phenylboronic acid and these thio-ligands have produced Ph.B (ONS) and Ph.B. (SNNS) type of biologically active complexes. These have been characterized by elemental analysis, molecular weight determinations, and conductivity measurements. Based on UV, IR, 1H NMR, 13C NMR and 11B NMR spectral studies, a tetracoordinated state of boron has been established in all the derivatives. The ligands and their corresponding organoboron complexes have been tested in vitro against a number of pathogenic fungi and bacteria and found to possess remarkable fungicidal and bactericidal properties. PMID- 2203881 TI - A model of gastric emptying in cats shows solid emptying is promoted by MK-329: a CCK antagonist. AB - The effect of MK-329, a potent, orally active, nonpeptidal cholecystokinin (CCK) antagonist, was measured on the gastric emptying rate of a solid meal in cats. External scintigraphy of cats that had been fed a meal of technetium-99m-(99mTc) labeled rabbit liver and light cream allowed the measurement of the emptying rates of either the liquid or solid portion of a meal under physiologic conditions. In cats, liquids emptied 2.6 times faster than solids [163 +/- 11 min vs. 62 +/- 3 min (mean +/- s.e.)]. At 3 or 10 mg/kg p.o., MK-329 gastric emptying was significantly accelerated, with the mean half-time of emptying being decreased by 34 +/- 11% (mean +/- s.e.) of the control half-times (p less than 0.02). Using only responders (five of six animals), mean half-time was decreased by 55 +/- 4% of the control half-times. CCK is important in regulating the emptying of solid food from the stomach because the CCK antagonist MK-329 accelerates that emptying. PMID- 2203882 TI - Immunoscintigraphy of human tumors transplanted in nude mice with radiolabeled anti-ras p21 monoclonal antibodies. AB - Anti-ras p21 monoclonal antibody (RASK-3) was used for immunoscintigraphy of human cancer cell lines in nude mice. Iodine-125-labeled RASK-3 was injected into nude mice with either human colon cancers (FCC-1 or BM-314) or lung cancer (KNS 62). Clear images were obtained in all three cancers 7 days after the injection of antibody. No localization of 125I-labeled control monoclonal antibody was observed. The ratio of tissue/blood radioactivity and % ID/g in the tumor were significantly higher than other organs by Day 8. The specific localization index examined by 131I-RASK-3 and 125I-control monoclonal antibody was also higher in the tumor than in other tissues. In the in vitro study, binding of RASK-3 to tumor cells increased significantly by treatment of cells with either lysolecithin or periodate-lysine-paraformaldehyde, which confirmed the intracellular localization of ras p21. The mechanism by which anti-ras p21 antibodies accumulate in tumor sites could be the necrotic changes in tumor cells or changes in membrane permeability of non-necrotic cells. These results provide a strong rationale for the utilization of ras p21 as a target antigen in the imaging of a variety of human cancers. PMID- 2203883 TI - A model to facilitate interactive planning. AB - The IPEM has helped stakeholders in a very complex tertiary medical center to understand the importance of interactive planning. The need to do so was highlighted by nursing demand and shortage issues. Deliberate efforts to refine and to restructure patient care within a hospital necessitates multidisciplinary planning and problem solving, collaborative nurse/physician relationships, and sound recruitment/retention policies. The experience at one hospital shows how nurse executives can take ownership of issues that help to reduce nursing supply and demand problems. Restructuring of patient care is one method of addressing demand; supply can be addressed locally by collaborative relationships with schools of nursing to increase students' access to education. Enhancing professional nursing practice is the responsibility of nursing service executives as well as educators. Yet, ultimately, it is the hospital's professional environment and reward system that influences nurses' choice of practice setting. PMID- 2203884 TI - Strategic management: a new dimension of the nurse executive's role. AB - The growth of corporate orientation for health care structures, with a focus on bottom-line management, has radically altered the role of nurse executives. With the organization's emphasis on performance, productivity, and results, successful nurse executives are now integrating the management of the delivery of nursing care with the management of complex corporate structures and relationships. The editor of Executive Development discusses the rapidly changing expectations and demands of the contemporary nurse executive's work. The nurse executive's role can be viewed from many perspectives: its scope, its value, its structure, its content. Content--"What does the nurse executive do that makes a real difference?"--is the focus here. PMID- 2203885 TI - Reconstruction of the temporomandibular joint with cryopreserved cartilage and freeze-dried dura: a preliminary report. AB - A technique for total reconstruction of the temporomandibular joint using cryopreserved cartilage and freeze-dried dura is described. The rationale, indications, and surgical technique are discussed. The technique has been used in nine joints in seven patients, followed between 3 and 27 months. There was one total failure of the graft, with the remainder maintaining good, asymptomatic joint function. PMID- 2203886 TI - Principles of surgical risk assessment of the elderly patient. AB - Treatment of the elderly will comprise increasingly higher proportions of practice time in the future, and issues regarding this treatment are more salient now than ever before. Because more elders are seeking treatment, surgeons need to be comfortable with assessing the potential risks associated with surgical procedures in their elderly patients, many of whom have multiple chronic diseases. Risks that need to be considered are those physiologic changes normal for aging, pathologic changes due to disease, and psychosocial changes that may occur with aging. This article assesses the contribution each of these changes makes to surgical risk, and discusses the principles of gerontology and geriatric medicine that are relevant to risk assessment. PMID- 2203887 TI - Liposarcoma: report of a case and review of the literature. AB - Liposarcoma of the head and neck region is extremely rare. An additional case of pleomorphic liposarcoma of the buccal mucosa is reported, representing an even rarer combination. The importance of combined radiation and radical surgical therapy as a means of improving survival is emphasized. PMID- 2203888 TI - Breast milk jaundice. PMID- 2203889 TI - Pathophysiology and dietary treatment of the glycogen storage diseases. PMID- 2203890 TI - Food, mucosal immunity, and IgA nephropathy. PMID- 2203891 TI - Unifocal stricture of the common bile duct in two children: a localized form of primary sclerosing cholangitis. AB - A 4-year-old boy and a 14-year-old girl referred for a cholestatic syndrome were found to have a unifocal stricture of the extrahepatic bile duct. Both radiological (endoscopic-retrograde-choledocopancreatography) and histological findings were suggestive of primary sclerosing cholangitis. There was no past history of chronic inflammatory bowel disease nor any other disorder. Serum autoimmune markers were negative. Complete remission was observed after surgical drainage, and both patients remained symptom-free after a follow-up of 12 months and 8 years, respectively. Such unifocal form of the disease may have a better prognosis than the plurifocal disease. The absence of associated disorders and autoimmunity may also be an indicator of better prognosis in these patients. PMID- 2203892 TI - Malabsorption due to protracted diarrhea. PMID- 2203894 TI - Transdermal iontophoresis of gonadotropin releasing hormone (LHRH) and two analogues. AB - Gonadotropin releasing hormone (GnRH), as well as an antagonist [Ac-D2Nal,1 D4ClPhe,2 D3Pal,3 NicLys,5 DNicLys,6 ILys,8 DAla10] GnRH.HOAc (1) and a superagonist [DTrp6, Pro9-NHEt]GnRH (2), have been electrochemically driven across excised hairless mouse skin. Determined by HPLC analysis, the delivery rate from aqueous solution into isotonic saline at 0.5 mA cm-2 was as high as 19 nM cm-2 h-1 for 2. Because of its insolubility in water, analogue 1 could only be delivered from an acidic donor solution. Analogue 2 was also delivered in pulsatile fashion using current on/off cycles. For all three peptides, passive transport was negligible and stability is evident when in contact with the stratum corneum. Slow metabolism occurs when GnRH contacts the dermal side of hairless mouse skin. PMID- 2203893 TI - Reproductive responses of male Microtus montanus to photoperiod, melatonin, and 6 MBOA. AB - Juvenile male Microtus montanus were examined for the effects of photoperiod, melatonin, and the naturally occurring reproductive stimulant 6-MBOA on growth and sexual maturation. 6-MBOA, present in sprouting grass, is an important environmental cue used for the initiation of reproduction in natural populations of this species. Long photoperiod (16:8) was stimulatory to body, testes, and seminal vesicle growth, while short photoperiod (8:16) inhibited these parameters. The pineal hormone melatonin, administered via daily afternoon injections (5 micrograms), was also inhibitory to all of the above parameters as well as to serum testosterone. 6-MBOA, administered via injection (0.0001-100 micrograms) or dietary means (0.1 or 1.0 microgram/gm unsifted chow), appeared unable to augment the rate of maturation in long-photoperiod-stimulated animals. When short-photoperiod animals were treated with high doses of the compound (100 micrograms injected or 1.0 micrograms/gm sifted chow), body and gonadal growth was inhibited to a greater extent than when animals were exposed to short photoperiod alone, and serum LH was reduced. Lower doses of the compound had no effect. Melatonin-treated animals experienced less maturational inhibition when simultaneously given a low dose of 6-MBOA-coated chow (1.0 micrograms/gm unsifted chow). A higher dose of 6-MBOA (1.0 micrograms/gm sifted chow) was ineffective in preventing the response to melatonin. These results indicate that 1) male M. montanus utilize photoperiod, rather than 6-MBOA, as a primary environmental cue, 2) high doses of 6-MBOA can be inhibitory under short photoperiod, 3) juvenile male voles are highly sensitive to the inhibitory effects of exogenously administered melatonin, and 4) 6-MBOA can partially prevent the inhibitory effects of melatonin on growth and sexual maturation. PMID- 2203895 TI - Sustained release of insulin by double-layered implant using poly(D,L-lactic acid). AB - This report describes the advantage of double-layered implants using low molecular weight poly(DL-lactic acid) in the sustained release of insulin. The double-layered implant consisted of a polymer matrix containing insulin and a polylactic acid layer which was coated partially on one of the surfaces of the insulin:polymer matrix. The double-layered implants were compared with single matrix implants from the standpoint of the in vitro dissolution test and in vivo performance. In vitro release rates were controlled by changing the amount of poly(DL-lactic acid) used in the polymer layer. In an in vivo test using diabetic animals, the double-layered implants provided a sustained release of insulin for 19 d, as judged by the changes in blood glucose levels and serum insulin levels after the subcutaneous implantation. PMID- 2203896 TI - Intravenous nicotine replacement suppresses nicotine intake from cigarette smoking. AB - Insofar as smokers regulate body levels of nicotine, nicotine replacement is expected to suppress the desire to smoke a cigarette. Our study was designed to test the hypothesis that i.v. replacement of nicotine will suppress daily intake of nicotine from ad libitum cigarette smoking and to compare the physiological effects of prolonged exposure to nicotine infused i.v. to the effect of smoking cigarettes throughout the day. Eight subjects received a 14-hr infusion of deuterium-labeled nicotine dosed to achieve levels of nicotine similar to those while smoking cigarettes for each individual (average, 33.1 mg; range, 17.7-49.9 mg) or saline (placebo). Cigarette smoking was permitted as desired. Nicotine infusion did not significantly affect the number of cigarettes smoked or the amount of tobacco burned, but nicotine intake from cigarette smoking was suppressed in all but one subject by an average of 24.6% (range, 4.0-51.2%). Down regulation of levels of nicotine while smoking in response to infusion of nicotine was imprecise, which may be a result of psychosocial factors influencing smoking behavior along with the development of tolerance to toxic effects of nicotine as a consequence of prolonged exposure to nicotine. Intravenous nicotine and cigarette smoking increased average heart rate and blood pressure throughout the day and 24-hr urinary epinephrine excretion to a similar extent. Despite higher levels of nicotine when subjects smoked during infusion of nicotine, there were no additional nicotine-related effects. No adverse effects were noted; most subjects could not distinguish nicotine from saline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203897 TI - Hippocampal mossy fiber denervation induces a supersensitivity to cholecystokinin of CA3 pyramidal neurons in the guinea pig but not in the rat. AB - Immunohistochemical studies have revealed the presence of cholecystokinin (CCK) in the guinea pig hippocampal mossy fiber projections, but this peptide appears to be absent in this system in the rat. However, in both species the mossy fiber system shows a strong opiate-like immunoreactivity. The present electrophysiological studies were undertaken to determine, in the two species, the effect of a unilateral colchicine-induced mossy fiber denervation, by comparing the responsiveness of target pyramidal neurons to Met-enkephalin, CCK and the nonpeptidic excitatory agents acetylcholine, kainate, quisqualate and ibotenate, on the intact and on the lesioned side. In both species, the colchicine lesion induced an increased responsiveness to Metenkephalin in the CA1 area, whereas no change was found in the neuronal responsiveness to the other excitatory agents tested. In the rat, the responsiveness of CA3 pyramidal neurons to kainate was reduced by 90%, those to the other excitatory agents were unchanged. In the guinea pig, the mossy fiber denervation induced a 10-fold increase of the responsiveness of CA3 pyramidal neurons to CCK, but did not modify their response to Met-enkephalin, kainate, quisqualate, ibotenate and acetylcholine. These results are consistent with the lack of CCK-like immunoreactivity in the mossy fiber projection to the CA3 region of the rat and with previous reports suggesting the presynaptic location of kainate receptors in this region. They provide novel evidence for the physiological role of CCK in the hippocampal mossy fiber projection in the guinea pig. PMID- 2203898 TI - Hemodynamic effects of adenosine agonists in the conscious spontaneously hypertensive rat. AB - The present studies examined the underlying hemodynamic mechanisms contributing to the reduction in blood pressure observed in conscious spontaneously hypertensive rats after systemic administration of adenosine agonists. The effects produced by i.v. and i.a. injections of 2-phenylaminoadenosine [CV-1808, adenosine (A2) selective agonist], 5'-N-ethylcarboxamide adenosine (NECA, nonselective agonist), 2-chloroadenosine (2-CADO, A1 selective agonist) and cyclopentyladenosine (CPA, A1 selective agonist) were evaluated and compared to those of hydralazine. All agents produced hypotensive effects after bolus i.v. injection. Although CPA, NECA and 2-CADO elicited dose-dependent bradycardia, CV 1808 and hydralazine increased heart rate. These effects, with the exception of the hydralazine-evoked responses, were attenuated by prior treatment with 8-(p sulfophenyl)theophylline (2 mg/kg/min), whereas both CV-1808 and hydralazine produced regional vasodilation, significant increases in blood flow occurred only after CV-1808 (3-30 micrograms/kg). The regional hemodynamic responses to NECA were more complex; low doses (0.1-1 microgram/kg) produced consistent reductions in regional vascular resistance, whereas at the highest dose renal vasoconstriction occurred. Although regional vasodilation occurred after 2-CADO, mesenteric vasoconstriction was observed subsequent to CPA administration. Whereas a significant increase in renin release was evident in animals treated with CV-1808 and hydralazine, no change occurred in response to the NECA-, 2-CADO or CPA-induced hypotension. We conclude that the predominant hemodynamic response after selective activation of A2 receptors is one of regional vasodilation and hypotension leading to a reflex increase in heart rate and renin release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203899 TI - Isomers of 12-hydroxy-5,8,10,14-eicosatetraenoic acid reduce renin activity and increase water and electrolyte excretion. AB - A metabolite of arachidonic acid, 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12 HETE), which can be formed either in the 12-S or 12-R configuration, has a diversity of biological actions and is generated by a number of tissues including the renal glomerulus and the vasculature. As the two isomers have been shown to differ in their effects on epithelial transport mechanisms and vascular responsiveness, we studied their direct effects on the rat isolated kidney, perfused for four consecutive 15-min clearance periods at a pressure of 90 mm Hg with a modified Krebs' buffer containing oncotic agents. At a dose of 20 nmol, both 12(S)- and 12(R)-HETE doubled urine volume (P less than .05) and sodium and potassium excretion rate in the first, postinjection clearance period. The effects of 12(R)-HETE were sustained during all three post-treatment clearance periods, whereas those of 12(S)-HETE were short-lived, excretion rates being similar to control values by the second post-treatment clearance period. At a higher dose of 40 nmol, 12(R)-HETE significantly reduced the usual rate of decline in glomerular filtration rate, characteristic of the rat isolated kidney, and caused an even greater initial increase in urine volume and sodium excretion rate than that achieved with 20 nmol. Renin concentration in the venous effluent was reduced immediately by 12(R)- and 12(S)-HETE (P less than .01), to approximately half of the control value. Again the response to the (R)-isomer was more prolonged. Thus, a 12-HETE of glomerular origin may alter renal function through direct and indirect tubular and hemodynamic effects. PMID- 2203900 TI - Inhibition of carbachol-induced inositol phosphate accumulation by phencyclidine, phencyclidine-like ligands and sigma agonists involves blockade of the muscarinic cholinergic receptor: a novel dioxadrol-preferring interaction. AB - The effect of phencyclidine (PCP) on carbachol-induced phosphoinositol hydrolysis was examined in rat brain slices taken from cortex, caudate-putamen and hippocampus. In all three regions studied, PCP significantly inhibited carbachol induced [3H]inositol phosphate accumulation working as low as 10(-6) M in the cerebral cortex. Because PCP has been shown to act at two sites, a PCP-site and a sigma site, various PCP-like agonists [levoxadrol (Lev), dexoxadrol (Dex) and MK 801 [(+)-5-methyl-10,11-dihydro- 5H-dibenzo(a,b)cyclo-hepaten-5, 10-imine maleate]] as well as sigma agonists [(+)-SKF10047 and 1,3-di(2-toly)guanidine (DTG) were examined for their effects on carbachol-induced phosphoinositol hydrolysis. All but MK-801 significantly inhibited the carbachol action; however, their order of potencies, Lev greater than or equal to Dex much greater than PCP greater than or equal to DTG greater than or equal to (+)-SKF10047 differed from those of other known PCP interactions at PCP and sigma sites. Inasmuch as it is known that PCP competes for binding at muscarinic sites, we examined the effects of PCP, Lev, Dex, DTG and MK-801 on the binding of L-[3H]-3-quinuclidinyl benzilate to its muscarinic site. All blocked L-[3H]-3-quinuclidinyl benzilate binding and exhibited a rank order of potency almost identical to that obtained in the inositol studies with Lev greater than Dex much much greater than DTG much greater than PCP MK-801. In addition, the IC50 values obtained from both studies were very similar. It is concluded that PCP, PCP-like compounds and sigma agonists block carbachol-induced inositol-phosphate accumulation by blockade of muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203901 TI - What's new in surgery: otolaryngology. AB - It is a decade since the last review article on otolaryngology in this Journal. In that time there have been significant advances in the practice of an ever changing specialty which originally started off as a surgical specialty designed to drain abscesses from the bony boxes in the head, namely the mastoids and the sinuses. It is impossible, in an article like this, to do anything other than superficially indicate the changes but a list of further reading is given for each section. PMID- 2203902 TI - Alterations in respiratory mechanics following thoracotomy. AB - Major alteration in respiratory mechanics occur in all patients following anaesthesia and thoracotomy because of a decrease in the functional residual capacity with minimal change in the closing volume leading to airway closure during tidal breathing and atelectasis. Diminished pulmonary reserve, because of non-pulmonary and pulmonary risk factors before operation, and/or restrictive ventilation and abnormal pattern of breathing due to postoperative pain sustain and aggravate these changes. These can proceed to postoperative pulmonary complications in some normal, and in many high risk, patients. Detection and correction of pre-existing pulmonary disease, smoking, sepsis and obesity is essential to reduce postoperative morbidity and mortality. Effective postoperative regional analgesia minimizes impairment of pulmonary function, aids in its recovery, and prevents postoperative pulmonary complications. The adjuvant use of chest physiotherapy and incentive spirometry should also help in decreasing the adverse affects of anaesthesia and surgery on the chest and thereby reduce the frequency and severity of postoperative complications. PMID- 2203903 TI - Femoral head sclerosis as a presentation of reticulum cell sarcoma of the femoral neck. PMID- 2203904 TI - Diet and large bowel cancer. PMID- 2203906 TI - More than a century of army medical statistics. PMID- 2203905 TI - Surgery of the ethmoids--past, present and future: a review. PMID- 2203907 TI - Ethics in clinical development. PMID- 2203908 TI - The genetics of idiopathic torsion dystonia. PMID- 2203909 TI - EL BUSCA and the value of signals in the diagnosis of dysmorphic syndromes: good and bad handles in computer assisted differential diagnosis. AB - A computer system for the assistance of syndrome diagnosis in dysmorphology (EL BUSCA) was developed, and used to test the mechanics of the diagnostic process. EL BUSCA has a reference file (REF) with 200 syndromes, expressed in 175 signals. Signals have a weight value resulting from the difference between the number of syndromes including that sign and the total number of syndromes in the REF. A mean signal weight was calculated for each syndrome. The system was tested with 200 published cases (CASES), representing 82 different syndromes. Each consultation (CONS) entered up to 15 patient signals. The system then selected syndromes having three or more of those signals. 'Present' (REF+CASE), 'Absent' (REF only), and 'Additional' (CASE only) signals, as well as the score given by the sum of the weights of 'present' signals, were displayed for each suggested diagnosis. A consultation was successful (positive answer) if the correct diagnosis appeared among the first 12 ranked. EL BUSCA gave a positive answer in 82% of the 200 test consultations. Linear regression, with ranking of the correct diagnosis among the answers as the dependent variable, was used for the analysis of the following results. For the REF, no relationship was found for either the number or the mean weight of the signals with the ranking of the correct diagnosis. For the CASES, there was a linear relationship between the number of signals of each consultation and the ranking of the correct diagnosis, indicating that the larger the number of signals consulted, the lower the ranking of the correct diagnosis. No effect was seen for the mean weight of consulted signals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203910 TI - Microwaves for microscopy. AB - Sample preparation for microscopy is based on physical and chemical processes. These processes can be influenced by microwave irradiation. The prerequisite for the development of good microwave procedures is knowledge of histochemistry combined with understanding of the physics of microwave irradiation. Examples of superior results of fixation, processing, and (immuno) staining performed in the microwave oven are presented, both for light- and electron microscopy. PMID- 2203911 TI - Spare the spleen: rationale and techniques. AB - For many years, a role for splenic function could not be established. Myths and folklore took the place of fact when it came to the spleen. Currently, splenic function is known to be important enough to justify surgical efforts that repair rather than excise the spleen after traumatic injury. Various repair techniques have been described, including many procedures that are appropriate to severe fragmenting splenic trauma. In a review of the experiences of 48 patients following splenorrhaphy using a variety of repair procedures, satisfactory results were achieved in 16 cases using a polyglycolic acid mesh wrap for splenic envelopment and parenchymal tamponade. There were no treatment failures or intra abdominal infections associated with this newly described procedure. PMID- 2203912 TI - From the Centers for Disease Control. Nursing home outbreaks of invasive group A streptococcal infections--Illinois, Kansas, North Carolina, and Texas. PMID- 2203914 TI - Insulin injections: rotation of anatomic regions and plasma glucose. PMID- 2203913 TI - Neurological injuries in boxers: the use of tests. PMID- 2203915 TI - The unsung public health hero who helped launch the war on tobacco. PMID- 2203916 TI - [bcl-2 gene involved in Japanese follicular lymphoma]. AB - Using three chromosome 18-specific DNAs, rearrangements of a bcl-2 gene were detected in 20 (44%) of 45 Japanese patients (pts) with follicular lymphoma (FL) and 3 (8%) of 36 pts with diffuse large cell lymphoma. The 21 pts had t (IgH; bcl 2), and of the remaining two who did not display it, one had chromosome t(14; 18). Compared with the findings in American pts, the lower frequency of t(14; 18) positive lymphoma could reflect a difference in the incidence of overall nodal B lymphoma between Japan and the United States. 11 of 18 pts with t(14; 18) positive FL expressed CD10 antigen on the cell surface and all 12 pts with t(14; 18)-negative FL did not, and the difference is statistically significant, indicating that t(14; 18)-positive Japanese FL is the same disease entity as most of American FL. Extra 18q- chromosome found in the advanced grade diseases of t(14; 18)-positive lymphoma results in amplification of the rearranged bcl-2 gene on 18q-, suggesting that the change is closely associated with transformation of FL carrying t(14; 18). It is thus possible of international realization to institute the prognostic factors and the treatment strategy for conquering t(14; 18)-positive lymphoma. PMID- 2203917 TI - [Chronic lymphocytic leukemia in Japan]. AB - Forty-one patients diagnosed as having B-cell chronic lymphocytic leukemia in Japan were evaluated. Patients were classified into five groups (CLL, CLL-L, CLL/PL, PLL, LSCL) according to differential counts of small lymphocytes, large lymphocytes, prolymphocytes, immunoblasts and/or lymphosarcoma cells among the lymphoid cells in the first available peripheral smears based on Melo's morphological criteria. Patients with typical CLL, defined as having more than 90% small lymphocytes, were seven (17%) of 41 patients. Phenotypical characteristic of CLL and its subgroups in Japan was considered to be the high expression of activated antigens, such as CD22, PCA1 and CD25. This finding may support the relatively higher proportion of atypical CLL with high percentage of large lymphocytes or prolymphocytes in Japan than that in Western countries. The molecular biological analysis revealed the deletion of C mu gene in one allele in three sIg-negative cases. The incidence of CLL, CLL-L and CLL/PL in Japan was deduced to be 1/10 of that in Western countries. PMID- 2203918 TI - [Comparison among three preconditioning regimens for allogeneic bone marrow transplantation in hematological malignancies]. AB - We analysed probability of disease free survival (DFS) and remaining in remission (POR) in evaluable patients with hematological malignancies undergoing allogeneic bone marrow transplantation by Nagoya BMT groups between 1976 and August 1989 according to conditioning regimens retrospectively. Patients were divided into good risk patients with acute leukemia in first remission or CML in chronic phase and high risk patients with advanced disease. The results are as follows: 1. DSF and POR in good risk patients was 45% and 68% at 7 1/2 years for thirty nine patients treated by CY + TBI, 63% and 78% at 5 2/3 years for thirty nine patients treated by CA + CY + TBI, 84% and 84% at 2 years for sixteen patients treated by preconditioning regimens without TBI respectively. 2. DFS and POR in high risk patients was 21% and 45% at 6 years for twenty nine patients treated by CY + TBI, 23% and 48% at 4 5/6 years for forty patients treated by CA + CY + TBI, 64% and 74% at 2 years for eight patients treated by preconditioning regimens without TBI respectively. 3. There were no statistical differences among these conditioning regimens in good and high risk patients. These results show that more effective and stronger preconditioning regimens are needed especially for high risk patients for prevention of posttransplant leukemia relapses. PMID- 2203919 TI - [Existence and significance of T-lymphoid crisis of chronic myeloid leukemia]. PMID- 2203920 TI - [The induction of differentiation of myeloid antigen positive acute lymphoblastic leukemia by phorbol ester (TPA) or GM-CSF]. AB - In 8 cases of myeloid antigen positive (My+) ALL (L2), morphology and phenotype of their blasts and the differentiation-inducing effect of each of 12-o tetradecanoyl phorbol-13-acetate (TPA) or recombinant GM-CSF (rGM-CSF) on the blasts were analysed. Five cases expressed common ALL phenotype such as CD19+, CD20-(-)+, CD10+, DR+ and c-mu-(-)+, and also My antigens such as CD11c+, CD11b+, CD14+ and CD13+ (B+My+ALL). One case expressed T-ALL phenotype such as CD5+, CD2+, CD3+, CD8+, CD4+ and CD10+ and also My antigen such as CD14 and CD13 (T+My+ALL). These six cases were diagnosed as biphenotypic ALL. The other 2 cases expressed mainly My antigen such as CD11c+, CD11b+, CD14+, CD13+, CD33+ and DR+, and one of the two expressed also CD2 (B-T-(-)+My+ALL). TPA induced the marked morphological change to monocyte-macrophage like cells and the increase of CD11+ cells in both of B-T-(-)+My+ALL cases. rGM-CSF transformed the blasts to large cells or cells with azurephilic granules in B+My+ALL cases. PMID- 2203921 TI - [Malignant melanoma in children--case presentation and statistical analysis]. AB - Malignant melanoma is a well documented but rare occurrence in children. We reported a case of a 10-month-old girl with malignant melanoma arising in a giant congenital nevocellular nevus. A giant mole on the lumbar and gluteal legion had been present since birth. Six month later, a nodular legion within the giant nevus started to growth slightly. The skin nodule were widely excised and grafted. Histological examination showed a malignant melanoma. The tumor located only in dermis. An enlarged lymph node of her left inguinal was removed. The histology revealed metastases from the melanoma. She died of metastases eight months after removal of the primary tumor. To our knowledge, only 37 documented cases of malignant melanoma in children under fifteen years of age have been previously reported, to which we add our case. In Japan, two-thirds of childhood melanomas arise de novo, which are clinically and biologically analogous to adult melanomas. The other third arises in large congenital nevocellular nevus which likely lead to death within two to three years of diagnosis. A majority of at least half of malignant melanoma in large congenital nevocellular nervus arise in children under 10 years of age. ALM types of malignant melanoma which are common in adult are rare in childhood melanomas. PMID- 2203922 TI - Clostridium botulinum in the soil of Paraguay. AB - Seventeen soil samples of Paraguay were examined for the presence of Clostridium botulinum. Botulinum type A, C1 and F toxins were detected in soil cultures. Type E toxin was not detected in any of soil cultures including those from river and lake shores. PMID- 2203923 TI - Thermoregulation and body fluids: role of blood volume and central venous pressure. AB - Dehydration due to hyperthermia induces both hyperosmolality and hypovolemia. Hyperosmolality reduces evaporative cooling, and alters the thermal responsiveness of the hypothalamic center to changes in both the central and peripheral milieu. Hypovolemia also reduces the thermoregulatory response, but its effect is more variable. The potential sensor of hypovolemia is the CVP, which is influenced by redistribution of blood volume, changes in blood volume, and alterations in cardiac function. The control of CVP is related to the regulation of vascular compliance, stressed blood volume, and unstressed blood volume. Vascular compliance is also involved in the regulation of fluid shifts between the ISF and the intravascular fluid space, and buffers changes in the CVP. Regulation of fluid replacement after thermal dehydration can be considered both from the point of view of osmoregulation and volume regulation. In the rehydration process, control of plasma osmolality precedes blood volume regulation, which also suggests that changes in blood volume sensed as changes in the CVP are regulated within a narrow range by various mechanisms. These findings suggest a hierarchic structure for the homeostatic mechanisms related to thermoregulation, with higher priority being given to the maintenance of cardiac output and the cellular volume of the brain at the expense of peripheral circulation and cell volume. PMID- 2203924 TI - A human-mouse hybrid cell line expressing both human leukocyte and histocompatibility-2 antigens. AB - Clone-1d, a sub-line of mouse L cells, was transfected with E. coli neo gene cloned in pSV2 vector (pSV2 neo) to obtain C1-1d neo cells. These cells are able to survive in the presence of geneticin (G418) but are killed by the medium containing hypoxanthine, aminopterin, and thymidine (HAT) because of the deficiency of thymidine kinase (TK) gene. By using these cells, it became possible to produce stable hybrid cells between these neo cells and any other cells since the hybrid cells are selected in the culture medium containing both G418 and HAT. We produced such hybrid cells by fusing C1-1d neo and A431 human epidermoidal carcinoma cells and studied the expression of human leucocyte antigens (HLA) and histocompatibility-2 antigens (H-2) in three hybrid cell lines. We found that one out of three hybrid cell lines expresses both HLA and human beta 2 microglobulin besides H-2 antigens, whereas the other two express only H-2 antigens; this indicated better stability of mouse genes than of human genes. PMID- 2203925 TI - [A case of foreign body granuloma after aortic valve replacement]. AB - A patient who developed a foreign body granuloma three years after aortic valve replacement was surgically treated. Oxidized cellulose was suspected of its cause. PMID- 2203926 TI - [The role of erythrocytes in the pathogenesis of functional disorders of blood platelets in patients with ischemic heart disease and the possibilities of their pharmacological correction]. PMID- 2203927 TI - [Surgical treatment of patients with combined lesions of the coronary and brachiocephalic arteries]. PMID- 2203928 TI - [Effect of labetalol on hemodynamics and oxygen consumption in patients in the early period of myocardial infarction]. AB - Effects produced both by single intravenous drop-by-drop labetalol, 1 mg/kg (29 patients), sublingual obsidan, 20 mg (14 patients) and a 3-day course treatment with labetalol, 200-600 mg/day, and obsidan (80-160 mg/day) on systemic, intracardiac, and regional hemodynamics and oxygen supply of the body were comparatively studied in 43 patients in early periods of myocardial infarction. As compared with obsidan, labetalol caused favourable hemodynamic changes mostly pronounced in patients with concurrent arterial hypertension. The hemodynamic effects in arterial hypertension were found to come about by virtue of largely an alpha-adrenoblocking effect of the agent whereas in the absence of hypertension it was beneficial due to a combined alpha- and beta-adrenoblocking effect. PMID- 2203930 TI - [Effect of a new anti-arrhythmia drug allapinin on hemodynamics in patients with a persistent form of atrial fibrillation before and after restoration of sinus rhythm]. AB - Echocardiographic study was performed in 24 patients with persistent atrial fibrillation (PAF) without clinical signs of circulatory failure. When treated with allapinin , all the patients with PAF showed a significant increase in heart rate (HR) and cardiac output (CO) and a decrease in total peripheral vascular resistance (TPVR). No substantial changes in the major hemodynamic parameters were found in patients with higher left ventricular dimensions; however, a significant rise in end systolic volume (ESV) was noted. There was significantly lower HR, diminished ESV, higher stroke volume and increased CO, elevated ejection fraction and TPVR with sinus rhythm. In PAF patients without apparent signs of circulatory failure, hemodynamic effects of allapinin may be accounted for by its direct vasodilatory action on the arterial bed and by its ability to affect cardiac autonomic innervation. A moderate cardiodepressive effect of the agent may be reflected by deteriorated latent signs of myocardial incompetence which are levelled off following sinus rhythm recovery. PMID- 2203929 TI - [Administration of solcoseryl in the complex treatment and intrahospital rehabilitation of patients with myocardial infarction]. AB - Clinical efficacy of solcoseryl was studied in 58 patients with acute myocardial infarction. Forty patients receiving no solcoseryl were included into a control group. The agent contributed to a reduction in the frequency of anginal episodes, a more rapid improvement of circulatory failure signs, and an increase in exercise tolerance. PMID- 2203932 TI - [The use of laser technology in general and abdominal surgery]. PMID- 2203931 TI - [Effectiveness of the cooperative program of multifactorial prevention of ischemic heart disease (results of the 3-year study)]. AB - The paper provides the results obtained in the course of the cooperative All Union programme on multifactor prevention of coronary heart disease (CHD), which has been implemented over 3 years to examine the efficiency of preventive actions aimed at correcting the levels of CHD risk factors. The study was conducted in 6 centers of the country among a non-organized male population aged 40-59 years. The outcome of the preventive measures, largely nonpharmacological ones, made during 3 years suggests that the prevalence of the major CHD risk factors may be reduced in the population. The preventive actions are the most beneficial in arterial hypertension and smoking. PMID- 2203933 TI - [Thal's operation in stenosing reflux esophagitis]. AB - The surgical treatment of esophageal strictures, developing on the basis of reflux esophagitis keeps on being an unsolved problem. A review of the literature is made and Thal's operation is given due consideration. The first successfully operated patient by this operative technique in Bulgaria is reported. The patient has been under observation, and the result of the operation is good. PMID- 2203934 TI - [Local anesthetic effect and subjective tolerance of 0.5% levobunolol in normal eyes]. AB - In a randomized, prospective, parallel double-blind clinical trial with positive and negative placebo control, the corneal sensitivity of 30 subjects with normal eyes was measured using the Cochet & Bonnet esthesiometer prior to and 1, 3, 6, 10, 15, and 30 minutes after topical application of levobunolol 0.5% (Vistagan 0.5% Liquifilm, Pharm-Allergan Vertrieb GmbH, Karlsruhe; 20 eyes). Proxymetacain 0.5% (proparacaine 0.5%, Ursapharm, Saarbrucken; 10 eyes) served as a positive, NaCl 0.9% as a negative control substance (placebo). Indomethacin 1% (Chibro Amuno 3, Chibret Pharmazeutische GmbH, Munich; 10 eyes) was tested as a further control substance. The subjects assessed the subjective tolerance of the test substances on a 4-point scale. Levobunolol 0.5% caused a statistically significant reduction in corneal sensitivity, attaining its maximum effect in the first minute after application and lasting on average for 6 minutes. The reduction was greater than that caused by timolol 0.5% and approximately one-half of that caused by betaxolol 0.5%. Proxymetacain 0.5% reduced corneal sensitivity to below the upper limit of the Cochet & Bonnet esthesiometer (200 mg) for up to 10 minutes. After 30 minutes, corneal sensitivity reverted to its initial value in all subjects. NaCl 0.9% eye drops did not decrease corneal sensitivity. After one minute an increase in corneal sensitivity (exercise effect) was observed which was significant as compared to the initial value as of the 15th minute after application. Indomethacin 1% likewise failed to reduce corneal sensitivity. In subjects with normal eyes, levobunolol 0.5% causes only a slight reduction in sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203935 TI - [Melanocytoma--a case report]. AB - The present paper reports on a case of melanocytoma with extensive visual field defects in a left eye. Fluorescein angiography, sonography, and computerized tomography showed the tumor to be located in the prelaminar part of the optic disk. There was no sign of infiltrative growth. There has been no change in the findings in the 9 months since the diagnosis was established. PMID- 2203936 TI - [Amplification of N-myc in neuroblastoma: paradigm for clinical use of an oncogene alteration]. AB - Increase of the dosage of cellular oncogens by DNA amplifications is a frequent genetic alteration of cancer cells. The presence of amplified cellular oncogenes is usually signalled by conspicuous chromosomal abnormalities, "double minutes" (DMs) or "homogeneously staining regions (HSRs). Some human cancers carry a specific amplified oncogene at high incidence. Particularly in neuroblastomas and in breast cancers the amplification of cellular oncogenes has been found associated with aggressively growing cancers and is an indicator for poor prognosis. Neuroblastoma, a malignant tumor of the sympathetic nervous system of children, frequently carries amplification of the oncogene MYCN. The amplification of MYCN is of predictive value for identifying high risk neuroblastoma patients that require specific therapeutic regimen and is generally viewed as the first oncogene alteration that turned out to be of practical clinical significance. PMID- 2203937 TI - Control of blast cell proliferation and differentiation in acute myelogenous leukemia by soluble polypeptide growth factors. AB - Proliferation of acute myelogenous leukemia (AML) derived blast cells requires the presence in culture of one or more growth factors. In the majority of cases Interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM CSF) stimulate clonogenicity of AML blasts, which can be synergised by Interleukin-6 (IL-6), Interleukin-1 (IL-1) and granulocyte colony-stimulating factor (G-CSF). In contrast, macrophage colony-stimulating factor (M-CSF) favors deterministic divisions. A substantial part of AML samples have clonogenic cells which, however, proliferate autonomously in vitro. The production by leukemic cells of a variety of growth or synergizing factors including GM-CSF, G-CSF, IL 1, IL-6, and Tumor Necrosis Factor (TNF) has been demonstrated and a fraction of cases will use these molecules to support clonogenic growth in an autocrine or paracrine fashion. However, unlike the situation with retrovirus-induced murine or avian leukemias, the role of production of CSFs and other cytokines by human leukemic cells in the transformational process remains uncertain. PMID- 2203938 TI - [Incidence, clinical markers and prognostic significance of immunologic subtypes of acute lymphoblastic leukemia (ALL) in children: experiences of the ALL-BFM 83 and 86 studies]. AB - In the therapy studies ALL-BFM 83 and 86, immunophenotyping of ALL by monoclonal antibodies was performed in a total of 1162 protocol patients (ALL-BFM 83 n = 578; ALL-BFM 86 n = 584). Both studies yielded similar results with respect to the incidence of immunological subtypes: CD10-negative pre-pre-B ALL (ALL-BFM 83: 3.6%; ALL-BFM 86: 5.3%), common ALL (80.1%; 77.9%), B-ALL (1.9%; 2.8%), pre-T/T ALL (13.9%; 13.5%). Leukemic cells of 3 patients in the ALL-BFM 83 study lacked lymphoid and myeloid antigens (acute unclassifiable leukemia, 0.5%), and 3 patients in the ALL-BFM 86 study exhibited different blast populations with expression of either myeloid or lymphoid features (acute mixed-lineage leukemia, 0.5%). Coexpression of myeloid antigens (CD13 and/or CD33 and/or CDw65) on lymphoblasts (My-positive ALL) was identified in 35 of the 570 (6.1%) protocol patients prospectively analyzed in the ALL-BFM 86 study. The following associations were observed between the immunological subtype and the clinical risk factors: median age (years)-pre-pre-B 3.0, common 4.3, B- 7.9, pre-T/T-ALL 8.5 (pre-pre-B, common vs. pre-T/T-ALL p = 0.05); median leukocyte counts (x 10(9)/l)-pre-pre-B 80, common 9.1, B- 12.3, pre-T/T-ALL 68.1 (common, B- vs. pre pre-B, pre-T/T-ALL p less than 0.05). The prognostic relevance of the immunophenotype was evaluated on the basis of the therapeutic results obtained in the ALL-BFM 83 study. A significant difference in the remission rate was only recognizable between patients with common ALL (99.1%) and those with pre-T/T-ALL (93.7%, p less than 0.001). After a median follow-up of 54 months, the probability of event-free survival is 71% for pre-pre-B ALL, 67% for common ALL, 56% for pre-T/T-ALL and 27% for B-ALL (common vs. B-, pre-T/T-ALL p less than 0.001), the prognosis in patients with pre-pre-B and common ALL being markedly influenced by the initial leukocyte counts and the age. PMID- 2203939 TI - Low grade malignant non-Hodgkin's lymphomas and peripheral pleomorphic T-cell lymphomas in childhood--a BFM study group report. AB - Non-Hodgkin's lymphomas (NHL) are classified as low or high grade malignant lymphomas of either B or T cell origin. Cells of low grade malignant NHL (LG-NHL) of B cell type represent either follicular or postfollicular, cells of LG-NHL of T cell type postthymic maturation stages in the lymphoid differentiation pathway. LG-NHL often fail to undergo long-term complete remission or cure in adults, no matter what type of conventional therapy is applied. In three pediatric therapy studies frequency and probability of continuous complete remission (pCCR) were studied for LG-NHL and peripheral pleomorphic T-cell lymphomas (PTCL). Of 432 evaluated patients only six children (1.4%) were qualified as LG-NHL. LG-NHL of T cell type were diagnosed in three children (one T-zone lymphoma, two PTCL of small cell type), LG-NHL of B cell type in another three cases. Two children presented with nodular type of centroblastic/centrocytic lymphoma (CB/CC), one with lymphoplasmocytoid type of immunocytoma (IC). In addition to the two patients with low grade malignant PTCL, there have been also four children with high grade malignant PTCL. The analysis showed that there was not significant difference for event free survival of children with LG-NHL and HG-NHL, respectively (pCCR: 0.63 and 0.82, p = 0.29). In contrast, when comparing high and low grade PTCL versus all other types of childhood NHL (non-PTCL), a significant difference seems to exist (pCCR for PTCL: 0.44, for non-PTCL: 0.83; p = 0.02). However, for further concisive conclusions more patients are needed for evaluation. PMID- 2203940 TI - The role of chemotherapy in the treatment of children with neuroblastoma stage IV: the GPO (German Pediatric Oncology Society) experience. AB - 340 consecutive patients with neuroblastoma stage IV were analyzed for the possible impact of chemotherapy on general condition, remission status, event free survival and survival. The children entered the trials NB 79, NB 82 and NB 85 of the German Pediatric Oncology Society (GPO). The patients did benefit from chemotherapy by considerable improvement of the general condition, by achievement of 30-40% complete and 60-70% partial remissions. The event free survival (EFS) rate 5-8 years after diagnosis was 13% for all 299 protocol patients, the survival (S) rate 10%. The median/mean EFS time were 11.6/23.8 months, the median/mean S time 17.0/29.4 months. The use of response rates as early predictors for long term survival is challenged. Addition of PCVm (cisplatinum, cyclophosphamide, Vm 26) to ACVD (adriamycine, cyclophosphamide, vincristine, dacarbazine) in trial NB 82 resulted in an improvement of the long term EFS rate from 5% to 18% (S rates 7----21%). The introduction of IVp (ifosfamide, VP16) and increase of doses (cisplatinum, Vm 26) did not further improve the results. Maintenance therapy (NB 82) revealed a positive influence on the outcome. Shorter intervals for realization of chemotherapy were associated with a trend for better EFS (NB 85). Although the group of children with bone marrow transplantation showed better EFS and S data compared to the unselected chemotherapy group, the advantage was less clear if matched pairs (remission status at the time of BMT) were compared.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203941 TI - [Use of a new silicon chamber system for carrying out immunologic technics with blood and bone marrow samples and histologic specimens]. AB - We are reporting for the first time on the successful application of the newly developed method of Silicon-Chamber-System (SCS). For this purpose we are utilizing a commonly manufactured silicon sealant by which we are able to obtain reaction fields of any size and number. We are applying the sealant on cell- and on tissue-slides without any special preparation. These reaction fields on the slides allow us to immunohistochemically analyse cells with multiple different monoclonal antibodies without running great risk of a cross-reaction between the different immunoreagents. It is a simple inexpensive and convenient method, giving us the opportunity to analyze elaborate cell material. PMID- 2203942 TI - "Suppressor genes; restraint of growth or of tumor progression"? PMID- 2203943 TI - Immunocytochemical and biochemical evidence of renin in human lactotrophic cell cultures. AB - Primary cell cultures from human prolactin (PRL)-secreting adenomas were used to test the ability of human lactotrophs to synthesize renin in vitro. The renin content of the culture medium and of cellular extracts was measured by enzyme linked immunosorbent assay. The level of PRL release in the culture medium and the amount of PRL in a cellular extract were determined by radioimmunoassay. Morphologic studies included indirect immunofluorescence, pre-embedding immunoelectron microscopy using a three-layer peroxidase-antiperoxidase method and postembedding immunoelectron microscopy using protein A-gold complexes. Renin was detected in cellular extracts and was found to be absent in the culture medium, whereas PRL was extracellularly secreted. PRL and renin immunoreactivity was observed in all the cultures studied by immunofluorescence. The subcellular localization of renin was found to be similar to that of PRL and was observed in the rough endoplasmic reticulum, the Golgi apparatus, and cytoplasmic secretory granules. The results suggest that, in vitro, renin may be synthesized and intracellularly metabolized in human adenomatous lactotrophic cells rather than secreted. Cell cultures may be a useful model to further the understanding of the role of a local renin-angiotensin system in PRL secretion. PMID- 2203944 TI - A rapid and simple color test for detection of salicylate in whole hemolyzed blood. AB - Acetylsalicylic acid (ASA) is still one of the most commonly used therapeutic agents. Salicylic acid, the major metabolite of ASA, can be detected easily in urine using simple chemical spot tests such as ferric chloride or Trinder's reagent. In forensic cases, urine is often not available and the rapid detection of salicylate in whole hemolyzed blood can be difficult. This report describes the rapid and simple detection of salicylate using ferric chloride and a methanolic extract of whole blood. The color test is rapid and can detect salicylate at mid-therapeutic concentrations of 5 mg/dL. As little as 300 microL of whole blood is required and no equipment is needed. The color test can also be used with serum or plasma. PMID- 2203945 TI - A rapid, sensitive, and specific screening technique for the determination of cyanide. AB - A colorimetric method for the screening of cyanide in biological specimens is presented. Cyanide in a 200-microL sample is diffused in a Conway 3 compartment dish into the center well where it catalyzes the reaction between p nitrobenzaldehyde and o-dinitrobenzene. The resulting blue-violet color intensity is proportional to cyanide concentration. The reaction is specific for cyanide, and concentrations as low as 0.05 mg/L can readily be detected. PMID- 2203946 TI - A pyroelectric thermal imaging system for use in medical diagnosis. AB - The value of infra-red thermography in a number of pathologies, notably rheumatology and vascular diseases, is becoming well established. However, the high cost of thermal scanners and the associated image processing computers has been a limitation to the widespread availability of this technique to the clinical community. This paper describes a relatively inexpensive thermographic system based on a pyroelectric vidicon scanner and a microcomputer. Software has been written with particular reference to the use of thermography in rheumatoid arthritis and vasospastic conditions such as Raynaud's phenomenon. PMID- 2203947 TI - A dual-sensor diagnostic pacemaker for ambulatory cardiac monitoring. AB - Unexplained blackouts are a very common medical problem. Some patients presenting themselves at hospital with such symptoms have underlying bradycardia or extreme tachycardia with a profound decrease in cardiac output. Modern treatment of these patients may be highly effective but accurate diagnosis of their exact condition may be needed. A novel ambulatory dual-sensor diagnostic pacemaker has been developed to meet this requirement. The device monitors intracardiac ECG and intraventricular pressure through a special lead introduced perveneously into the right ventricle and detects and counts events such as bradycardia, tachycardia, pauses in the electrical or pressure signals and electrical interference. Analogue recordings of the electrical and pressure waveforms of 16 of these events can be made during the operating period of 3 weeks and pacing is incorporated via a specially-adapted commercial pacemaker if a prolonged episode of bradycardia or a pause is sensed. The device forms part of a complete diagnostic system also incorporating a computer which is used to set up the parameters of the diagnostic pacemaker and to display and analyse the recorded data. PMID- 2203948 TI - Contradictory effects of uncomplicated versus complicated abdominal surgery on the hepatic capacity for urea synthesis in rats. AB - Female Wistar rats weighing 217 g were subjected to two types of surgical stress: uncomplicated (hysterectomy) and complicated (spleen and uterus ligated, crushed, and left in situ). Liver function as assessed by amino-N conversion was measured as the capacity for urea-N synthesis preoperatively (control animals) and on Days 1, 3, and 6 postoperatively. Uncomplicated surgery transiently increased the capacity for urea-N synthesis by 30% the first postoperative day (P less than 0.001). Complicated surgery decreased the capacity for urea-N synthesis to 55% throughout the investigation period (P less than 0.001). This was not due to a general change in liver mass since galactose elimination capacity remained constant. The increase in the capacity for urea-N synthesis after uncomplicated surgery is probably due to glucagon since plasma glucagon increased whereas plasma insulin and blood glucose remained unchanged after amino acid loading. The persistent decrease in the capacity for urea-N synthesis in complicated surgery is not due to changes in these regulators: glucagon increased, insulin decreased, and the rats were hypoglycemic. All changes are expected to increase the capacity for urea-N synthesis. The mechanism for the emergence of these two distinct metabolic patterns is not known. The phenomenon is probably important for interpretation of metabolic data on clinical stress. PMID- 2203949 TI - Tumor necrosis factor production by Kupffer cells requires protein kinase C activation. AB - Tumor necrosis factor (TNF) has been proposed as a primary inflammatory mediator of septic shock. In vitro and in vivo studies indicate that endotoxin- or lipopolysaccharide (LPS)-activated macrophages are a principle source of TNF; however, membrane signal transduction and intracellular pathways by which LPS triggers TNF production in macrophages are unclear. Recent evidence indicates that specific protein phosphorylation via activation of protein kinase C (PKC) is an early, critical step in the signaling of macrophage TNF production by phorbol esters. We hypothesize that PKC activation is also required in LPS-signaled Kupffer cell (KC) TNF production. Murine KCs were obtained by liver perfusion and digestion and then stimulated with LPS (Escherichia coli O111:B4) or LPS in the presence of H-7, a selective PKC inhibitor. Conditioned media was collected at 3 hr for assay of TNF utilizing the L929 cytolysis bioassay standardized to murine rTNF-alpha. We found that H-7 inhibited significantly LPS signaled TNF release at a concentration of 10 microM, while H-8 (a cyclic nucleotide specific inhibitor) had no effect. The effect of H-7 was dose dependent and present at varying concentrations of LPS. Down regulation of PKC activity by preincubation of KCs with phorbol myristate acetate (PMA, a direct activator of PKC) also resulted in significantly reduced TNF release after LPS stimulation. The inhibitor H-7 (10 microM) also significantly inhibited LPS signaled prostaglandin E2 release in Kupffer cells. Total and specific intracellular protein phosphorylation was determined by trichloroacetic acid precipitation and SDS-polyacrylamide gel electrophoresis after labeling stimulated Kupffer cells with 32Pi. Total protein phosphorylation was not significantly altered by LPS stimulation; however, autoradiograms from PMA- and LPS-stimulated KCs demonstrate enhanced phosphorylation of a 40-kDa protein (2.7 +/- 0.9-fold) and a 33-kDa protein (3.1 +/- 1.0-fold) which were inhibited by H-7. We conclude that activation of PKC and protein phosphorylation are required steps in the signal transduction pathway of LPS-stimulated TNF production in Kupffer cells. PMID- 2203951 TI - [Splenic cysts: indications for surgery and surgical procedures]. AB - Based on a late physical examination of 18 patients with splenic cysts, we discuss symptoms, diagnostics and indication to operate and the procedure of operation. We found no specific symptoms. The ultrasound is the most important diagnostic method and may be supplemented by computerized axial tomography. The indication depends on the symptoms, the diameter within the organ and, most important, the dignity of the cyst. For pseudocysts we prefer resection of the cyst wall, because it is a simple and safe procedure. Splenectomy is the treatment of choice for cysts with unknown dignity. PMID- 2203950 TI - [Suppression of exocrine secretion does not lead to disruption of endocrine function of pancreas transplants]. AB - The adequate management of the exocrine secretion of vascularized pancreas transplants is still controversial. Basically, the exocrine graft secretion may either be suppressed by obstruction of the pancreatic ducts or preserved by drainage into the recipient's enteric or urinary tract. In a model of isogenic pancreas transplantation in streptozotocin diabetic rats the impact of preserved versus suppressed exocrine secretion on the quality of endocrine graft function was investigated. Preservation of the exocrine secretion was accomplished by pancreaticoduodenal transplantation, while duct ligation was used to suppress the exocrine secretion. Endocrine graft function was monitored by determination of non-fasting blood glucose levels, intravenous glucose tolerance tests, peripheral insulin levels, water and food intake as well as urine and faeces production. Suppression of the exocrine graft secretion induced acinar atrophy, proliferation of pancreatic ducts, interstitial cell infiltration and fragmentation of islets of Langerhans, while drainage of the exocrine graft secretion completely preserved the architecture of the transplant. Despite the fundamental structural changes induces by exocrine suppression no deterioration of endocrine graft function was noted within the observation period of one year. Both techniques were equally effective in ameliorating the diabetic hyperglycemia, hypoinsulinemia, reduced glucose tolerance, polydipsia, polyphagia, polyuria and restored normal growth rate and general health of diabetic pancreas graft recipients. Thus it can be concluded that suppression of the exocrine secretion does not impair the quality of endocrine function of pancreas transplants. PMID- 2203952 TI - [Resection method and functional reconstructive surgery of malignant soft tissue tumors of the extremities]. PMID- 2203954 TI - Familial vocal cord dysfunction associated with digital anomalies. AB - Familial vocal cord dysfunction is a rare condition that has been reported in only a few instances. This is a report of identical male twins, both of whom had congenital bilateral abductor vocal cord paresis associated with finger deformities. The vocal cord paresis progressed to paralysis that required tracheotomy, then returned to a slowly resolving paresis during which the vocal cords had uncoordinated motion generally known as synkinesis. Another male sibling and the mother had a history of stridor during infancy and finger deformities. Several other relatives had digital abnormalities, and an infant first cousin with finger abnormalities required a tracheotomy for vocal cord paralysis. PMID- 2203953 TI - [Technic of papilloduodenectomy]. AB - Local excision of preiampullary tumours first described in 1989 has been relegated in the background after introduction of pancreaticoduodenectomy in 1935. Recent reports suggest that ampullary excision may give good results. In order to define the place of this operation which may be a simple excision of the duodenal mucosa (ampullectomy) or a wide excision of the papilla encompassing the posterior duodenal wall and the distal bile and pancreatic ducts (papilloduodenectomy) it is important to make a clear distinction between these two techniques. We describe the technique of papilloduodenectomy and define the place of this operation, which may be useful in selected cases. PMID- 2203955 TI - Directory of otolaryngological societies. PMID- 2203956 TI - Curvularia/Drechslera sinusitis. AB - Sinusitis due to unusual fungal pathogens is thought to occur primarily in immunocompromised individuals. However, the fungi Curvularia, Drechslera, and others produce sinusitis in healthy young adults. The signs and symptoms produced by these organisms are usually considered to be complications of sinusitis. Of the three cases that we report, two manifested decreased visual acuity, and the third presented with acute onset of seizures. Computed tomography scans were helpful in delineating the extent of disease and in following the results of therapy. Aggressive surgical treatment is necessary; indeed, two of our cases required a second operation to eradicate all disease. If histopathology shows tissue invasion by the fungus, intravenous amphotericin B is recommended. Fungal cultures and smears should be obtained when healthy patients present with complications of sinusitis. PMID- 2203957 TI - Structural changes in the round window membrane following exposure to Escherichia coli lipopolysaccharide and hydrocortisone. AB - The present study focused on structural changes of the round window membrane (RWM) from agents that evoke transient or permanent impairment of the auditory brainstem response when applied into the RW niche. Escherichia coli (E. coli) lipopolysaccharide (LPS) in sterile water (SW) and a 2% suspension of hydrocortisone (CORT), micronized in SW, were instilled into the round window (RW) niche of Sprague-Dawley rats. The morphology of the RWM was analyzed 3 to 21 days after instillation of either substance. Both substances caused minor structural alterations at the light microscopic level. The RWM showed a slight thickening and an invasion of inflammatory cells. At the ultrastructural level, the CORT-treated specimens showed an increased epithelial height and numerous microvilli, whereas the epithelium of the LPS-treated specimens was extended and contained few microvilli resembling those in the normal RWM. We postulate that the RWM may undergo dynamic structural changes when exposed to various agents. The structural alterations per se can influence the passage of substances from the middle ear to the inner ear. PMID- 2203958 TI - Increased pressor effect of repeated doses of rat or porcine endothelin in the anaesthetised rat. AB - Rat and porcine endothelin differ by 6 amino acids. Porcine and rat endothelin were equiactive at producing the transient fall in blood pressure in the anaesthetised rat but porcine endothelin was three times more potent at producing the subsequent sustained rise. Repeated doses of either peptide in the same rat produced a larger pressor response with each repetition, the peak response being reached more rapidly. The magnitude of the blood pressure fall did not change significantly but the first response in each rat was of longer duration than subsequent responses, especially with rat endothelin. PMID- 2203960 TI - Neural control of airway function: new perspectives. PMID- 2203959 TI - Pathogenetic mechanisms of asbestos and other mineral fibres. PMID- 2203961 TI - A visit to the birthplace of modern nursing. PMID- 2203962 TI - Carboxy-terminal peptides from the B subunit of Shiga toxin induce a local and parenteral protective effect. AB - Two synthetic peptides corresponding to overlapping sequences from the C-terminus of the B chain of Shiga toxin were prepared and characterized. These peptides consisted of residues 54-67 and 57-67 in the protein sequence. This region coincides with the major peak of surface area residues, as predicted from a computer-derived plot. For the purpose of immunization, the peptides were either conjugated with a protein or a synthetic carrier, or were polymerized. Polyclonal antibodies against these peptides derivatives, induced in rabbits, recognized the homologous peptides and cross-reacted with the intact toxin. These antibodies were capable of neutralizing the various biological activities of the toxin, namely the cytotoxic, enterotoxic and neurotoxic activities. Active immunization of mice with the peptide derivatives protected them from the lethal effect of the toxin. Moreover, oral immunization of rats led to inhibition of fluid secretion in ligated ileal loops into which toxin was injected. This effect was paralleled by the induction of high levels of specific anti-peptide IgA antibodies in the serum after bile duct ligation. PMID- 2203963 TI - Surgery for epilepsy. AB - The National Institutes of Health Consensus Development Conference on Surgery for Epilepsy brought together neurologists, neurosurgeons, psychologists, other health care providers, and the public to address issues regarding epilepsy surgery including patient selection and management, localization of seizure site onset, appropriate diagnostic techniques, and postoperative outcome assessment. The panel concluded that brain surgery is an alternative treatment when medication fails. Seizure frequency, severity type, possible brain damage or injury from frequent seizures, and effect on quality of life all must be considered in deciding to evaluate for surgery. An appropriate medication trial must have been conducted, using the correct drugs for the patient's seizure type at adequate doses and blood levels. Non-epileptic attacks must be ruled out, and diagnostic tests to detect any underlying cause should be performed. If surgery is considered, patients should be evaluated by a team including neurologists, neurosurgeons, neuropsychologists, social workers, and, if needed, psychiatrists. Assessment of outcome should include standardized methods of information collection. Measures assessing quality of life and overall health status can compare epilepsy to other chronic conditions. Assessment of economic and social impact on the patient's family should be included. PMID- 2203964 TI - A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women. AB - Background. The effectiveness of calcium in retarding bone loss in older postmenopausal women is unclear. Earlier work suggested that the women who were most likely to benefit from calcium supplementation were those with low calcium intakes. Methods. We undertook a double-blind, placebo-controlled, randomized trial to determine the effect of calcium on bone loss from the spine, femoral neck, and radius in 301 healthy postmenopausal women, half of whom had a calcium intake lower than 400 mg per day and half an intake of 400 to 650 mg per day. The women received placebo or either calcium carbonate or calcium citrate malate (500 mg of calcium per day) for two years. Results. In women who had undergone menopause five or fewer years earlier, bone loss from the spine was rapid and was not affected by supplementation with calcium. Among the women who had been postmenopausal for six years or more and who were given placebo, bone loss was less rapid in the group with the higher dietary calcium intake. In those with the lower calcium intake, calcium citrate malate prevented bone loss during the two years of the study; its effect was significantly different from that of placebo (P less than 0.05) at the femoral neck (mean change in bone density [+/- SE], 0.87 +/- 1.01 percent vs. -2.11 +/- 0.93 percent), radius (1.05 +/- 0.75 percent vs. -2.33 +/- 0.72 percent), and spine (-0.38 +/- 0.82 percent vs. -2.85 +/- 0.77 percent). Calcium carbonate maintained bone density at the femoral neck (mean change in bone density, 0.08 +/- 0.98 percent) and radius (0.24 +/- 0.70 percent) but not the spine (-2.54 +/- 0.85 percent). Among the women who had been postmenopausal for six years or more and who had the higher calcium intake, those in all three treatment groups maintained bone density at the hip and radius and lost bone from the spine. Conclusions. Healthy older postmenopausal women with a daily calcium intake of less than 400 mg can significantly reduce bone loss by increasing their calcium intake to 800 mg per day. At the dose we tested, supplementation with calcium citrate malate was more effective than supplementation with calcium carbonate. PMID- 2203965 TI - Oral therapy for acute diarrhea. The underused simple solution. PMID- 2203966 TI - Assumptions of AIDS inquiry challenged. PMID- 2203967 TI - AIDS. Commission grows angrier. PMID- 2203968 TI - Academic freedom. Sex, racism and videotape. PMID- 2203969 TI - Family of disulphide-linked dimers containing the zeta and eta chains of the T cell receptor and the gamma chain of Fc receptors. AB - Stimulation of T cells by antigen activates many signalling pathways. The capacity for this range of biochemical responses may reside in the complex structure of the seven-chain T-cell antigen receptor (TCR). In addition to the complexity shared by all TCRs, coexpression of zeta (zeta) and the distinct but related eta (eta) chains creates structural diversity among the TCR complexes expressed on a given cell. In most murine T cells that we have studied, about 90% of the heptameric receptor complexes contain a zeta zeta disulphide homodimer, whereas 10% contain a zeta eta disulphide heterodimer. Recent studies suggest that zeta has a critical role in allowing antigen to activate the cell, whereas eta expression has been correlated with the capacity for antigen-induced phosphoinositide turnover. A third zeta-related protein, the gamma (gamma) chain of the Fc epsilon and some Fc gamma receptors, exists as a disulphide homodimer in those complexes. The structural relatedness of zeta and gamma is emphasized by the recent demonstration of zeta zeta in association with CD16 in TCR-negative natural killer cells. Here we identify T cells lacking Fc receptors but coexpressing zeta, gamma, and eta, document the formation of novel heterodimers between zeta and gamma and between eta and gamma and show their association with the TCR. A greater range of homologous coupling structures than previously thought may be one way of achieving the variety of TCR-mediated (and possibly Fc receptor-mediated) biochemical responses and effector functions. PMID- 2203970 TI - Microconversion between murine H-2 genes integrated into yeast. AB - Patchwork homology observed between divergent members of polymorphic multigene families is thought to reflect evolution by short-tract gene conversion (nonreciprocal recombination), although this mechanism cannot usually be confirmed in higher organisms. In contrast to meiotic conversions observed in laboratory yeast strains, apparent conversions between polymorphic sequences, such as the class I loci of the major histocompatibility complex (MHC), are short and do not seem to be associated with reciprocal recombination (crossover, exchanges). We have now integrated two nonallelic murine class I genes into yeast to characterize their meiotic recombination. We found no crossovers between the MHC genes, but short-tract 'microconversions' of 1-215 base-pairs were observed in about 6% of all meioses. Strikingly, one of these events was accompanied by a single base-pair mutation. These results underscore both the importance of meiotic gene conversion and sequence heterology in determining conversion patterns between divergent genes. PMID- 2203971 TI - Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs. AB - The aminoacyl-transfer RNA synthetases (aaRS) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction. These proteins differ widely in size and oligomeric state, and have limited sequence homology. Out of the 18 known aaRS, only 9 referred to as class I synthetases (GlnRS, TyrRS, MetRS, GluRS, ArgRS, ValRS, IleRS, LeuRS, TrpRS), display two short common consensus sequences ('HIGH' and 'KMSKS') which indicate, as observed in three crystal structures, the presence of a structural domain (the Rossman fold) that binds ATP. We report here the sequence of Escherichia coli ProRS, a dimer of relative molecular mass 127,402, which is homologous to both ThrRS and SerRS. These three latter aaRS share three new sequence motifs with AspRS, AsnRS, LysRS, HisRS and the beta subunit of PheRS. These three motifs (motifs 1, 2 and 3), in a search through the entire data bank, proved to be specific for this set of aaRS (referred to as class II). Class II may also contain AlaRS and GlyRS, because these sequences have a typical motif 3. Surprisingly, this partition of aaRS in two classes is found to be strongly correlated on the functional level with the acylation occurring either on the 2' OH (class I) or 3' OH (class II) of the ribose of the last nucleotide of tRNA. PMID- 2203972 TI - Medicine and the biological sciences: new vistas for verse. PMID- 2203973 TI - Goodpasture's syndrome revisited. A new perspective on glomerulonephritis and alveolar hemorrhage. PMID- 2203974 TI - Comment on Dr. Thorp's article. PMID- 2203975 TI - Cushing's syndrome during pregnancy. AB - Two cases of Cushing's syndrome during pregnancy are reported, both due to an adrenal adenoma. The association of pregnancy and Cushing's syndrome has up to now been described in 48 patients (including our two cases); Cushing's syndrome was ACTH-independent in 59%, ACTH-dependent in 33%, and of unknown cause in 8%. The obvious preponderance of ACTH-independent Cushing's syndrome in pregnancy--in contrast to the higher prevalence of ACTH-dependent Cushing's syndrome in the nonpregnant state--is unexplained, but might be related to less severe hypercortisolism in patients with adrenal adenoma. Active treatment of Cushing's syndrome in pregnancy is associated with a slightly but not significantly better outcome of pregnancy. PMID- 2203977 TI - Successful treatment of pulmonary lymphangioleiomyomatosis with oophorectomy and medroxyprogesterone-acetate: report of a case and brief review of the literature. AB - This report describes the successful hormonal treatment of a young woman with pulmonary lymphangioleiomyomatosis. In addition a brief review of the literature is presented. PMID- 2203976 TI - Cryptococcal meningo-encephalitis after prolonged corticosteroid therapy. AB - We present a case of a 69-yr-old woman who developed cryptococcal meningo encephalitis after 9 yr of corticosteroid therapy. The diagnosis was made on an India ink preparation and positive culture of the cerebrospinal fluid sediment. NMR-imaging was a useful tool for detecting intracerebral localisation of the infection. The patient was successfully treated with amphotericin B and flucytosine for 6 wk and with itraconazole for another 8 wk. PMID- 2203978 TI - Capnocytophaga canimorsus (formerly DF-2) infections: review of the literature. PMID- 2203979 TI - [The foramen of Monro--blockage caused by a giant aneurysm of the basilar artery. A case report and review of the literature]. AB - A case of a giant aneurysma of the basilar artery bifurcation with occlusive hydrocephalus due to bilateral foramen of Monro occlusion is reported. The patient presented with progressive neurological deterioration which led to computerized tomography examination and implantation of a ventricular shunt as an emergency procedure. After the patient had recovered to a certain extent, four vessel angiography was performed that demonstrated a giant basilar tip aneurysm. As the posterior communicating, the posterior cerebral as well as the superior cerebellar arteries originated from the aneurysm sac direct surgical attack as well as endovascular treatment was considered to be impossible. A permanent biventricular-abdominal shunt system was implanted and the patient was discharged. Three weeks later the patient was readmitted comatose after he had suffered a massive subarachnoid hemorrhage from which he finally died. The clinical and radiological signs, the differential-diagnostic considerations as well as the few cases of foramen of Monro occlusion by a giant basilar artery tip aneurysm, presented in the literature so far, are discussed. PMID- 2203980 TI - Pituitary metastases. AB - Over the past 12 years we encountered three histologically confirmed pituitary metastases. Primary cancer had been diagnosed and treated previously in only one patient. In the remaining two a transsphenoidal operation provided the initial diagnosis of metastasis, and the primary lesion was subsequently detected at autopsy in one. In two of the three patients symptoms and signs of pituitary dysfunction were the first manifestations of the malignant disease. The main symptoms and signs were impairment of visual acuity, visual field defect, headache, adenohypophyseal insufficency and diabetes insipidus. A sellar mass was demonstrated by CT or MRI in all patients. The tumours were all completely extirpated by subfrontal route in one case and transsphenoidally in the remaining two patients. Following surgery the presenting symptoms improved satisfactorily in all patients. PMID- 2203981 TI - [The deafferentation concept]. AB - Old and new findings on development and regression of the nervous system in relation to brain plasticity are presented as deafferentiation phenomena in the sensory, nociceptive, visual and auditory systems. Other applications of the deafferentiation concept are discussed. PMID- 2203982 TI - [Intracranial hematoma accompanying bleeding tendency: therapeutic practice and analysis of literature]. AB - Therapies and prognoses covering fifteen cases of intracranial hematoma (ICrH) accompanying various types of bleeding tendency (BTD) were studied along with a secondary analysis of the pertinent references. Fifteen cases were divided into two groups, Group A comprising 11 cases of ICrH accompanying primary BTD, and Group B comprising four cases of ICrH accompanying secondary BTD caused by various underlying diseases. Group A included four cases of hemophilia A (Hp-A), two cases of factor XIII deficiency (FXIII-d), three cases of thrombocytopenia (Th-p) and two cases of vitamin K deficiency (VK-d). The four cases of Hp-A responded favorably, with good prognoses, to a supplementary therapy alone. This result was endorsed by the development of therapy as documented in the references. The combined five cases of FXIII-d and Th-p tended without exception, to show good prognoses in the wake of a combination therapy of supplementary treatment and surgical procedure. As regards FXIII-d, there was an inter reference difference in supplementary doses. Many references shared the view that splenectomy was essential to the treatment of Th-p in general, and idiopathic thrombocytopenic purpura in particular. The current study also suggested that gammaglobulin in large doses would serve as an effective therapy. The two cases of VK-d suffered from a serious degree of lingering neurologic manifestations, although their lives were saved. Even though there is an established therapy for it, VK-d was found to be a problem with poor functional prognosis showing the importance of the preventive approach. Group B was classified into the acute type and the subacute type depending on the rate of pathologic development. As underlying diseases DIC and myelofibrosis due to acute myeloblastic leukemia, and Th-p due to aplastic anemia were noted in two cases in each group. Of these, two cases of the subacute type were able to be saved, while two cases of the acute type followed poor prognostic courses resulting, eventually, in death. The following were found to be responsible fatal factors: 1) causes of BTD which involved both mechanisms of coagulation and hemostasis, 2) non-removal of the underlying disease, in which case supplementary therapy tended to be futile, and 3) the underlying disease per se as a danger to the life of the patient. In conclusion, therapeutic rationale and prognosis in ICrH accompanying primary type of BTD will benefit from the implementation of an adequate augmentative therapy as in the ordinary type of ICrH.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2203983 TI - [A case of intracranial chondroma presenting with pontine hemorrhage]. AB - A rare case of parasellar chondroma accompanied by pontine hemorrhage is described. A review is made of the previously reported 6 cases of intracranial chondromas complicated with hemorrhage. A 21 year-old woman was admitted to our clinic because of consciousness deterioration progressing to coma within a day, and right hemiparesis. CT scan showed a contrast-enhanced mass in the parasellar region and a hematoma in the brain-stem, which was clearly demonstrated by MRI to be abutted on the dorsal part of the tumor mass. The tumor was removed through frontotemporal craniotomy and confirmed histologically as chondroma. Postoperatively, the patient gradually regained consciousness and is hospitalized to rehabilitate hemiparesis. PMID- 2203984 TI - [A case of foreign-body granuloma]. AB - A 24-year-old male patient was admitted to our Ryukyu University Hospital, complaining of visual disturbance. He had had partial removal of a suprasellar region tumor in another hospital one year before the admission. Microscopical findings had shown two cell patterns of germinoma in the first operation. Following it, the patient received irradiation with a total dose of 54Gy. The tumor completely disappeared after these procedures. On this admission, plain CT scan revealed an isodensity mass in the suprasellar cistern extending to the right side of the third ventricle, which was enhanced homogeneously. In MRI, the mass showed low intensity in the T1-weighted inversion recovery sequence, and heterogeneously, high intensity in the T2-weighted spin echo sequence. By bifrontal craniotomy, the tumor was removed. Histologically, it consisted of granuloma containing fine cotton fibers. MRI findings of intracranial foreign body granuloma were discussed. PMID- 2203985 TI - [Massive traumatic hematoma localized in the basal ganglia: treatment by CT guided stereotactic aspiration surgery]. AB - A case of massive traumatic hematoma of the basal ganglia which was treated successfully by CT-guided stereotactic aspiration surgery, was reported. A 6-year old boy was admitted 2 hours after a traffic accident. He had no neurological focal signs except for disturbance of consciousness on admission. CT scan revealed a massive hematoma in the right basal ganglia. His neurological status gradually deteriorated 6 hours after the trauma and the size of the hematoma increased on serial CT scan. Then, CT-guided stereotactic aspiration surgery was performed and about 15.5 ml of hematoma clot was successfully evacuated. He made an uneventful recovery from the operation and gradually improved. The final outcome was that he showed moderate disability at 3 months after the trauma. The possible mechanism of development of hematoma in this lesion, and indication of CT-guided stereotactic aspiration surgery were also discussed. PMID- 2203987 TI - [Malignancy of brain tumors]. PMID- 2203986 TI - [A case of systemic lupus erythematosus with subarachnoid hemorrhage due to ruptured aneurysm]. AB - A case of systemic lupus erythematosus (SLE) with subarachnoid hemorrhage due to a ruptured intracranial aneurysm is reported. A 31-year-old woman who had been treated with steroid for SLE was admitted to our department with severe headache, and nausea. CT scan showed subarachnoid hemorrhage and the left carotid angiogram revealed a small aneurysm at the supraclinoid portion of the left internal carotid artery. She had no neurological deficit. Hematological examination on admission showed disseminated intravascular coagulation (DIC), therefore, we decided to perform an intentionally delayed operation. In the meantime we treated the patient for DIC with FOY and methylprednisolone. The operation was performed after two weeks, when DIC had been eliminated completely. Postoperative hematological examination showed severe thrombocytopenia. We considered that SLE had come to the fore again, so we used Danazol in company with FOY and steroid. It seemed that Danazol was very effective for her. She was discharged about two months after admission with no problem. Cerebral apoplexy, such as cerebral infarction and cerebral hemorrhage, has often been seen in SLE, but subarachnoid hemorrhage due to a ruptured aneurysm is very rare. We could find only five reports of this phenomenon. Their prognoses were all, unfortunately, poor. It should be born in mind for therapy that a patient in SLE has a tendency to bleed. It seems that repeated hematological examinations and quick and proper management are important. We think that the aneurysmal formation in SLE is due to lupus vasculitis or the fragility of blood vessels due to a long use of Steroid. PMID- 2203988 TI - [Treatment of symptomatic vasospasm with GIK (glucose-insulin-potassium) infusion]. AB - GIK (glucose-insulin-potassium) solution has been administered to myocardial infarction patients as a polarizing therapy, but the effects of GIK administration on vasospasm after subarachnoid hemorrhage have never been reported. We used GIK solution to treat 7 cases of symptomatic vasospasm with congestive heart failure due to hypervolemia-hypertensive treatment. The GIK solution, composed of 200cc of 50% glucose solution, 250cc of water, 40 mEq of KCl, and 20 units of actrapid insulin, was administered continuously through a central venous catheter. The GIK therapy improved congestive heart failure following elevation of cardiac output in 7 cases, and simultaneously stabilized the serum glucose level within the range of 88-175 mg/dl. After GIK administration, remarkable improvement in the consciousness level was achieved in all cases, and cerebral infarction due to vasospasm appeared in only one case in spite of severe subarachnoid hemorrhage. It is thought that GIK therapy will be effective in the treatment of symptomatic vasospasm with congestive heart failure through the normalization of hemodynamics, the improvement of hyperglycemia and protection against cerebral ischemia. PMID- 2203989 TI - [Stereotactic aspiration using coordinate software for hypertensive intracerebral hematomas]. AB - Stereotactic aspiration for intracerebral hematoma has become widely used due to improvements in computed tomography (CT). CT-guided stereotactic aspiration for hypertensive intracranial hematomas was performed in 46 cases. Stereotactic aspiration with coordinate software was carried out among 16 cases. We compared the clinical results of conventional stereotactic aspiration with results of the new method using coordinate software. Using coordinate software, we can examine the route for the target point, as well as the target point of the hematoma before surgery. Therefore we can avoid obstacles such as ventricles and internal capsules. Further, we can aspirate hematoma by using only this one procedure. Mean hematoma aspiration percentage has risen from 44.9 to 87.2% by using coordinate software. Rate of drainage tube insertion after operation has decreased from 90 to 50%. The period of placement of the drainage tube and the frequency of infection due to the drainage tube has become lower, too. Therefore we can say that the outcome of treatment of hypertensive intracranial hematomas is improved by using coordinate software. PMID- 2203990 TI - [A case of intrasellar and suprasellar meningioma with hypopituitarism]. AB - A case of intrasellar and suprasellar meningioma with hypopituitarism is reported. A-64-year-old woman was admitted to our hospital with chief complaints of reduced consciousness and inactivity. She had a history of subarachnoid hemorrhage 20 years previously, and developed right third nerve palsy. Physical examination demonstrated that, in consciousness, she was stuporous, and she had impaired visual acuity and palsy in the right third nerve. An X-ray film of the sella turcica showed enlargement and intrasellar calcification. A CT scan with contrast enhancement revealed a homogenously enhanced mass in the sella and suprasellar region. A cerebral angiogram showed elevation of the bilateral A1 portion of the anterior cerebral artery. No tumor blush was evident. Endocrinologic function tests confirmed impaired anterior lobe hormones and hypothyroidism. Preoperative diagnosis was pituitary adenoma. The tumor was subtotally removed by using the transsphenoidal approach and right frontotemporal craniotomy was carried out using microsurgery in a two staged operation. The tumor was yellowish-grey, partly firm in consistency, and it had a soft elasticity. Operative findings showed that the dura matter of the tuberculum sella, the anterior and posterior clinoid process, the medial sphenoidal ridge, and the wall of the cavernous sinus were intact, which was confirmed at autopsy, later. Microscopical examination revealed a mixed meningothelial and fibroblastic meningioma with papillary component and psammomatous bodies. The tumor was thought to originate in the diaphragma sella, and to extend in intrasellar and suprasellar directions. The patient died of basilar artery thrombosis. In clinical and radiological examination, there is no definite difference between pituitary adenoma and intrasellar meningioma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203991 TI - [Glossopharyngeal neurinoma causing symptomatic hemorrhage: case report]. AB - A 86-year-old man was admitted to our hospital because of swallowing disturbance and deterioration of consciousness. He had been aware of hearing disturbance on the right side for twelve months. Computed tomography (CT) scan demonstrated an inhomogeneous hyperdense mass lesion, 3.2 X 2.3 cm in size, at the right cerebello-pontine angle, and ventricular enlargement with intraventricular hemorrhage. Skull tomogram revealed destructive enlargement of the right jugular foramen. The angiogram showed avascular mass with elevation of anterior inferior cerebellar artery, and downward shift of posterior inferior cerebellar artery. Operative and histological findings were compatible with glossopharyngeal neurinoma of Antoni type A dominance. This tumor had numerous abnormal vessels probably causing massive hemorrhage. Only fifteen cases of intracranial neurinoma with symptomatic hemorrhage have been reported in the world literature. This case is reported as the sixteenth one and the first glossopharyngeal neurinoma among them. Possible etiology of such hemorrhage is discussed. PMID- 2203992 TI - [Three cases of cryptic arteriovenous malformation in basal ganglia manifested by putaminal hemorrhage]. AB - Three cases of histologically proven cryptic arteriovenous (AV) malformation of the basal ganglia are reported. Seventeen cases of patients showing putaminal hemorrhage in the CT scan underwent craniotomy for evacuation of a hematoma between January 1986 and December 1988. The preoperative diagnosis was hypertensive putaminal hemorrhage. In all three cases a network of abnormal vessels around the internal capsule was detected at surgery. Case 1: A 62-year old male was admitted to our hospital with consciousness disturbance (JCS 20), total aphasia and right hemiparesis. The CT scan showed left putaminal hemorrhage. The volume of the hematoma was 45 ml by CT criteria. Left carotid angiography did not demonstrate any abnormal findings. Case 2: 69-year-old male was admitted with consciousness disturbance (JCS 10) and right hemiparesis. Left putaminal hemorrhage (volume 25 ml) was recognized on the CT scan. Two hours after admission, the consciousness level suddenly deteriorated (JCS 100). At that moment, the volume of the putaminal hematoma had increased to 100 ml. AV malformation was not detected by left carotid angiography. Case 3: A 50-year-old male was admitted with consciousness disturbance (JCS 20), total aphasia and right hemiparesis. The CT scan showed left putaminal hemorrhage of 73 ml. Pathohistological examination proved AV malformation in each case. The three cases described here suggest the following; 1) The incidence of the basal ganglia cryptic AV malformation has been considered low, but meticulous examination shows that among the cases diagnosed as hypertensive hemorrhage, AV malformation is not infrequently the hidden cause.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2203993 TI - Morphometric study of human cerebral cortex development. AB - Morphometric studies of immature cerebral cortex in humans show developmental changes extending up to the time of adolescence. Growth of dendrites and of synaptic connections occurs during infancy and early childhood. Excess synaptic connections are eliminated during later childhood years. The exuberant connections that occur during infancy may form the anatomical substrate for neural plasticity and for certain types of early learning. PMID- 2203994 TI - Individual variability in cortical organization: its relationship to brain laterality and implications to function. AB - The human brain and the brains of most mammals studied for this purpose demonstrate hemispheric asymmetry of gross anatomical landmarks and/or architectonic cortical subdivisions. The magnitude as well as the direction of these cortical asymmetries vary among individuals, and in some species there exist significant population directional biases. The magnitude, if not the direction, of cortical asymmetry is found to predict for relative numbers of neurons comprising a given pair of hemispheric architectonic homologues such that the more asymmetric the region is, the smaller the number of neurons. Similarly, the more asymmetric a region is, the smaller the density of interhemispheric connections and (probably) the greater the density of intrahemispheric connections. Developmentally, the decrease in the number of neurons characterizing the more asymmetrical regions appears to reflect mainly increased unilateral ontogenetic cell loss, and diminished callosal connectivity might signify increased developmental axonal pruning. These relationships between cell numbers, callosal connections, and presumed intrahemispheric relationships can be entertained to explain variability in anatomo-clinical correlations for language function and aphasia between left- and right-handers and men and women. PMID- 2203995 TI - Functional recovery following transplants of embryonic brain tissue in rats with lesions of visual, frontal and motor cortex: problems and prospects for future research. AB - In animals, fetal brain tissue grafts into damaged adult host brain reduce some of the functional deficits caused by brain lesions. Although neurons from transplants survive and develop reciprocal connections with host brain tissue, such connections are generally not enough to replace damaged fibers completely and support behavioral recovery observed. Moreover, grafts never exhibit a normal morphological appearance as compared to adult tissue, but some metabolic activity is occasionally detected within the transplant. Release and/or diffusion of trophic substances from the transplant, in addition to those from the damage host brain, may partially restore neuronal and behavioral functions especially after lesions of the visual cortex. In this case, it can be hypothesized that fetal transplants serve as "living mini-pumps". In addition, there is evidence that the combination of trophic substances (e.g. GM1 ganglioside) and fetal brain transplants may provide a better opportunity for recovery than either treatment given by itself. PMID- 2203996 TI - Functional organization of striatum as studied with neural grafts. AB - The function of the striatum has proved elusive. A structure which, at the gross microscopic level, appears homogeneous is now revealed to be heterogeneous in terms of its afferent and efferent relationships with cortex, limbic system and mid brain. Cerebral cortex projects topographically to caudate/putamen. Lesions to different cortical areas result in different behavioural impairments which are mirrored by selective neuronal or neurochemical lesions to the sectors of striatum receiving input from the cortex. Foetal neurones prepared from substantia nigra or striatum grafted to a damaged area of adult striatum reverse the lesion-induced behavioural impairments. Within different sectors of striatum the neurones and their afferent and efferent connections are defined to striosomes and matrix representing a finer grain of intrastriatal organization, the functional significance of which is unclear. It remains a challenge within such complex anatomical circuitry to discover the full extent of anatomical reintegration and functional compensation that can be achieved with grafts of foetal neurones. PMID- 2203998 TI - Chest trauma. How to detect--and react to--serious trouble. PMID- 2203997 TI - Autoradiographic localization of mas proto-oncogene mRNA in adult rat brain using in situ hybridization. AB - The cellular localization and the distribution of the mas proto oncogene/angiotensin receptor mRNA have been studied in the male rat brain using in situ hybridization with radiolabelled mas cRNA probes. Neuronal cell populations in the forebrain were selectively labelled. A strong specific labelling was demonstrated in the dentate gyrus, the CA3 and CA4 areas of the hippocampus, the olfactory tubercle (medical part), the piriform cortex and the olfactory bulb, while a weak to moderate labelling was present all over the neocortex and especially in the frontal lobe. PMID- 2203999 TI - A longitudinal study of Lancefield group A streptococcus acquisitions by a group of young Dunedin schoolchildren. AB - Paired saliva and pharyngeal cultures obtained on nine occasions over a 27-month period from a group of 103 young Dunedin schoolchildren were tested for beta haemolytic Lancefield group A streptococci. Approximately 20% of the 858 pharyngeal cultures and 5% of the saliva cultures were positive. Although group A streptococci were isolated at least once from 59 (57.3%) of the subjects, only seven cases of clinically apparent group A streptococcus pharyngitis were detected at the time of specimen taking. The study has shown that pharyngeal acquisitions of group A streptococci occur frequently in some young schoolchildren. Carriage of small numbers of group A streptococci in the absence of clinical symptoms of infection was common and in ten children the same type of group A streptococcus was consistently recovered from pharyngeal cultures over periods of more than 12 months. It remains unclear why some children do not seem to so readily acquire group A streptococci, while others develop serious delayed sequelae to these infections. PMID- 2204000 TI - [Anterior composites. A definitive restoration]. PMID- 2204001 TI - [Conometric crowns. The Korber technic]. PMID- 2204003 TI - Phase II study of pirarubicin in metastatic breast cancer. AB - Pirarubicin is a more lipophilic derivative of doxorubicin, with a higher uptake rate of cells, lower cardiotoxicity and better antitumor efficacy in preclinical models. Thirty-four patients with metastatic breast cancer were treated in a multicenter phase II study with pirarubicin (THP) using a dosage of 75 mg/m2/every 3 weeks. The patients had a median age of 56 years (range 41-73) and a performance status of WHO grade 0-2. Patients pretreated with anthracyclines, or who were older than 75 years and without sufficient bone marrow reserve were excluded. The 32 evaluable patients received a median number of 4 cycles (range 2 8). The myelosuppression was dose-limiting and led to infections (grades 1 and 2) in 5 patients. Twenty-eight patients developed leukocytopenia grade 3 and 4 toxicity and 7 patients experienced thrombocytopenia grade 1 and 2. The drug was subjectively well tolerated and nausea, vomiting and alopecia were mild. One complete remission with a duration of 15.4 months (67 weeks) and 7 partial remissions with a median duration of 9.3 months (40 weeks) were achieved, which resulted in an overall response rate of 25%. Twenty-one patients were stable for 17 weeks (median) under the treatment with pirarubicin. PMID- 2204002 TI - Possibilities and limitations of immunological marker analyses for the detection of minimal residual disease in childhood acute lymphoblastic leukemia. AB - Specific application of immunological markers in acute lymphoblastic leukemia (ALL) for detection of inadequate blast cell reduction after induction therapy or early recognition of a relapse requires a precise characterization of the immunophenotype at the time of diagnosis and an understanding of the biology of the disease. Therefore, the ALL-BFM 83 study is first used to demonstrate the incidence, antigen expression and dynamics of relapse occurrence of immunological subtypes in childhood ALL. This is then followed by a discussion of the different immunological features hitherto applied for identification of residual leukemia cells in ALL (terminal deoxynucleotidyl transferase--TdT; common acute lymphoblastic leukemia-associated antigen--CALLA, CD10; various T-cell differentiation antigens; kappa/lambda labelling); these are, however, not leukemia-specific and are expressed to varying degrees by normal lymphoid progenitor cells. The sensitivity of these analyses is therefore largely determined by the markers applied and the type of investigational material. Finally, suitable markers are presented for detecting residual leukemia cells in the different immunological subtypes of ALL. Their clinical relevance still remains to be evaluated in prospective therapy studies. PMID- 2204004 TI - Phase II evaluation of carboplatin in advanced esophageal carcinoma. A trial of the Phase I/II Study Group of the Association for Medical Oncology of the German Cancer Society. AB - Eighteen patients with advanced squamous cell carcinoma of the esophagus without prior chemotherapy were treated with carboplatin. Based on experimental data a split dose of carboplatin of 130 mg/m2 given on days 1, 3 and 5 was administered. In cases showing no WBC and platelet suppression, an escalated dose of 160 mg/m2 was proposed. Out of 18 evaluable patients no complete and partial responses were observed and there were only 5 patients with stable disease (27.8%) lasting 2-7 months. Therefore, carboplatin in the regimen used shows no meaningful antitumor activity in patients with advanced esophageal carcinoma. The escalated dose (mean 107-123% of the starting dose) was well tolerated and was followed by only minor gastrointestinal and hematological toxicity. Therefore, this regimen can be recommended for future trials. PMID- 2204005 TI - Etoposide, adriamycin, and cisplatinum (EAP) combination chemotherapy for advanced gastric cancer. A phase II trial by the "Chemotherapiegruppe Gastrointestinaler Tumoren (CGT)". AB - In a multicenter trial, 49 patients with histologically proven advanced gastric cancer were treated with a combination chemotherapy consisting of etoposide 120 mg/m2 d 4, 5, 6 adriamycin 20 mg/m2 d 1, 7 and cisplatinum 40 mg/m2 d 2, 8. Therapy was repeated every 4 weeks, 45 patients were evaluable for response after 8 weeks of treatment. Eight patients achieved a partial remission (PR: 18%), 17 patients had no change (NC: 38%), and 20 patients showed tumor progression (P: 44%). Four patients with primarily inoperable tumor and without distant metastases who achieved a partial remission, underwent second look operation with curative intention. All 4 patients died within 12 months after second look operation due to tumor recurrence. Median survival time of all patients was 9 months. Toxicity was considerable. WHO grade 3/4 toxicity appeared in 20-30% of patients (nausea, vomiting, loss of appetite, leucopenia). After 3 cycles complete alopecia was present in 70% of patients. Severe infection, requiring treatment, occurred in 10 patients. Five patients discontinued therapy because of intolerable subjective toxicity. The observed response rate of 18% objective partial remissions is disappointing and does not give support to the communications reporting response rates over 50% with EAP and other regimens including cisplatinum. In conclusion, and considering the high subjective and objective toxicity of this regimen, it can not be recommended for standard use in patients with advanced gastric cancer. PMID- 2204006 TI - [Combination therapy with adriamycin, cisplatin and vindesine in C cell carcinoma of the thyroid]. AB - Ten patients with advanced medullary thyroid carcinoma were treated with the combination of adriamycin (50 mg/m2), cisplatin (60 mg/m2) and vindesine (3 mg/m2). Only one partial remission (PR) was seen. There were six "no changes" and three "progressive diseases (PD)". Comparing with data from the literature the polychemotherapy of adriamycin, cisplatin and vindesine seems not to be superior to the mostly employed adriamycin-monotherapy. The tumor-markers calcitonin (CT) and carcinoembryonic antigen (CEA) were pathologically elevated in any case. During chemotherapy they proved to be valuable parameters of the course of the disease. In the patient with PR the CT- and CEA-serum levels reflected the clinical remission. In the patients with PD, however, they rose continuously. PMID- 2204007 TI - Bioavailability of cyclophosphamide in the CMF regimen. AB - Cyclophosphamide (CY) was administered to 22 breast cancer patients treated routinely according to the CMF regimen: 75 mg/m3/d x 14 d p.o. CY, 30 mg/m2 days 1 and 8 i.v. methotrexate (MTX) and 500 mg/m2 days 1 and 8 i.v. 5-Fluorouracil (5 FU). The sequence of drug administration was always the same: 1) CY, 2) MTX; and 3) 5-FU. Capillary gas chromatography was performed for determination of CY in blood. Bioavailability (F) could be determined in 14 patients since CY was also administered intravenously in the same dose. The data of systemic exposure of oral CY in the other 8 patients were matched to those of the first 14 in whom bioavailability could be determined. Mean F was 0.85 +/- 0.22 (85% +/- 22%); in 1 patient F was 0.43 (43%). Furthermore, 3 patients treated with only p.o. CY had low estimated F values: 0.45, 0.49 and 0.50. In comparing patient characteristics with pharmacokinetic data, it was concluded that age might have a predictive value for elimination half-life t 1/2 z of i.v. CY. The youngest patients showed shortest t1/2 z and were also amongst those with the lowest F. This indication requires an extension of the study as well as monitoring of CY metabolism as a function of age. For the premenopausal patients this might be of particular importance, since this group is known to be prone to benefit from chemotherapeutic treatment according to the CMF regimen. PMID- 2204008 TI - [Decreased plasma zinc levels in metastatic breast cancer]. AB - Zinc is an essential component of many metalloenzymes for DNA and proteinsynthesis including RNA and DNA polymerases. It has been shown by several investigators that zinc is accumulated in breast cancer tissues. To investigate a possible relation between plasma zinc levels and tumor load, plasma zinc levels were evaluated in 76 patients with non metastatic breast cancer (no evidence for disease after mastectomy) and in 66 patients with metastatic breast cancer. Zinc concentrations were measured in plasma using an atomic absorption spectrophotometer (normal range 80-150 mcg/dl). In patients with metastatic disease plasma zinc concentrations were in the lower region of the normal range or depressed (arithmetic mean: 84.9 SD 21.6 mcg/dl), whereas patients with non metastatic breast cancer had normal zinc levels (arithmetic mean: 126.0 SD 27.7 mcg/dl). The difference between the two groups was highly significant (p = 0.001, t = -9.742, 140 degrees of freedom). It is concluded, that plasma zinc in breast cancer patients is depressed according to the stage of the disease. Based on experimental data a substitution of zinc cannot be recommended. PMID- 2204009 TI - [Mucin-like carcinoma-associated antigen: sensitivity and specificity in metastatic breast cancer]. AB - The clinical usefulness of a tumor marker essentially depends on its sensitivity and specificity for a certain tumor. To prove, wheather the new tumor marker 'mucin-like carcinoma-associated antigen' could be used for the management of breast cancer patients, we determined its serum concentration in 50 healthy blood donors, 130 patients with various non-malignant diseases, 138 patients with different metastazised tumors and 137 breast cancer patients. 78 of the breast cancer patients had known metastases while 59 had no evidence of disease after initial surgical and adjuvant therapy. Only 2% of the blood donors and 3% of the patients with non-malignant diseases exceeded the cut-off level of 15 U/ml. In contrast to these findings, 28% of patients with various metastazised tumors and 77% of patients with metastazised breast cancer had serum levels above 15 U/ml. Breast cancer patients without evidence of disease had elevated marker values in only 3%. In breast cancer the serum levels of this antigen depends on the type of metastases. Maximal concentrations were found in mixed metastases while cutaneous or lymph-node metastases showed the lowest rate of positivity. Furthermore a good correlation of serial determined marker levels with the course of the disease was observed, so that we conclude, that mucin-like carcinoma-associated antigen can be used in follow-up of patients with metastazised breast cancer. Because of its high sensitivity and specificity it provides some advantage over other markers used in this disease. PMID- 2204010 TI - [Alpha 2-interferon in kidney cancer. Experiences with 6 patients]. AB - We report on 6 male patients with advanced renal cell carcinoma without prior chemotherapy. They were treated by recombinant alpha 2-interferon in a toxicity limited dosage. The maximal tolerated dose was 3 x 5 x 10(6) U/wk. to 3 x 20 x 10(6) U/wk., limited by flu-like symptoms in 5 cases, by thrombopenia in 1. We observed a response in 3 cases (2 partial remissions, 1 mixed response) lasting for 10, 11 and 13 months, respectively. This comparatively good result may be due to patient characteristics (little pretreatment, pulmonary metastasis, good performance status) as well as to a medium dosage. Occurrence of response after termination of interferon therapy in two cases are of particular interest. PMID- 2204011 TI - [Acute coronary thrombosis and myocardial ischemia following chemotherapy of Hodgkin's disease]. AB - A 37 year old man without coronary risk factors or known heart disease showed progression of Hodgkin's disease after radiation and multiple chemotherapy. One day after the first cycle of chemotherapy with methotrexate, Ifosfamide and etoposide, he had an acute myocardial ischemia. The creatinin-kinase was elevated up to 325 U/l. Coronary angiography showed a thrombus in the left anterior descending coronary artery (LAD), while the other coronary arteries were normal. Ventriculography showed an apical akinesia. After 7 days of treatment with heparin coronary angiogram was normalized, without any stenosis in the LAD. To our knowledge this is the first documented case of a coronary artery thrombosis and myocardial ischemia after chemotherapy in a patient without coronary heart disease. We conclude that chemotherapy can cause myocardial ischemia by coronary artery thrombosis in patients without prior heart disease. PMID- 2204012 TI - [Breast-sparing therapy in carcinoma of the breast. Indications and consequences. Results of a multidisciplinary consensus meeting]. PMID- 2204013 TI - [The role of inducing factors in early embryonic development]. AB - In the field of early embryonic induction and differentiation we can observe an exponential increase of research activities over the last three years. The reasons for this rapid exploration are the application of powerful techniques of molecular biology and molecular genetics and the recent accumulation of knowledge about the close functional correlation between growth factors, embryonic induction factors, the products of oncogenes (or proto-oncogenes), and transcription factors. The highly probable role of the cellular and viral oncogenes in regulation of the differentiation and function of normal and malignant cells has stimulated the interest of scientists working on the molecular basis of malignant cell transformation. An excellent model to study mesoderm and neural induction and differentiation on the cellular and molecular level is the embryo of the south African clawed frog (Xenopus laevis), which is now a favored vertebrate system in many laboratories. PMID- 2204014 TI - [The development of neuroendocrine regulation in ontogeny]. AB - Published and author's data on hypothalamic control over the most important endocrine functions during mammalian ontogenesis were reviewed. The data presented indicates that adenohypophyseotropic protein neurohormones are synthesized and accumulated in hypothalamus long before birth. At the end of the prenatal period most of hypothalamic neurohormones reached the adenohypophysis and were involved in regulation of the tropic hormones secretion. Exceptionally, regulative properties of thyroliberin and somatostatin are only manifested in immature-born animals (rats) in early postnatal period. PMID- 2204015 TI - [An immunohistochemical study of early embryogenesis in the clawed toad Xenopus laevis by using monoclonal antibodies to intermediate filament proteins]. AB - Distribution of cytokeratin epitopes was studied in X. laevis embryos at stages 10-25 using 5 monoclonal antibodies against proteins of the human and rat keratin filaments. Specific staining was observed in chorda, outer layers of ectoderm and presumptive epidermis (late gastrula), and inner layer of presumptive epidermis. The cells of the stained zone (presumptive epidermis) were compressed while the cells of unstained zone (presumptive neuroectoderm) were extended tangentially. PMID- 2204016 TI - [Parthenogenetic development in response to the treatment of mouse oocytes with a weak alkali. Experiments with methylamine]. AB - Ovulated mouse oocytes were incubated in methylamine-containing medium M16 for different periods of time. Methylamine appeared to activate oocytes, and most of them developed by haploid parthenogenesis. Methylamine action depended on its concentration and time of incubation. The data obtained suggest that the increase of intracellular pH unblocks meiosis and activates mammalian oocytes [correction of cocytes]. PMID- 2204017 TI - The murine c-rel proto-oncogene encodes two mRNAs the expression of which is modulated by lymphoid stimuli. AB - Here we report a survey of c-rel proto-oncogene transcription in murine tissues, cell lines and lymphoid cells. In addition to the previously described 7.5-kb mRNA, we have identified a mRNA of 2.5-kb. As DNA hybridization indicates that there is only one gene with significant homology to c-rel in the mouse genome, it appears that multiple mRNAs are transcribed from c-rel. The nucleotide sequence of a cDNA clone derived from the 2.5-kb c-rel mRNA demonstrates that the 7.5- and 2.5-kb mRNAs encode identical proteins. The different size of the two mRNAs is due to variation in the length of the 3' untranslated region, which arises from the use of alternate polyadenylation signals. These mRNAs are present at low levels in organs tested, and in cell lines representing a wide variety of lineages. Fibroblasts are the only cells in which expression was not detectable. In B-cell lines representing different stages of differentiation, the highest levels of mRNA are seen in B-lymphomas, and this level drops markedly in plasmacytomas. There is a transient increase of 10- to 20-fold in the level of c rel mRNAs in T-cells treated with concanavalin A, while lipopolysaccharide stimulated B-cells exhibit a transient 5-fold elevation of c-rel expression. This study indicates that the control of c-rel expression can vary between and within different cell lineages, and the widespread expression of this gene points to a fundamental cellular function, rather than one restricted to hematopoietic cells as previously suggested. PMID- 2204018 TI - The chicken cellular progenitor of the v-ets oncogene, p68c-ets-1, is a nuclear DNA-binding protein not expressed in lymphoid cells of the spleen. AB - The chicken cellular c-ets-1 locus encodes for two related proteins generated by alternative splicing: the widely expressed p54c-ets-1 protein and the cellular homolog of the v-ets-encoded domain of the E26-transforming protein P135gag-myb ets, p68c-ets-1 which has been found so far only in the spleen. We have prepared a new site specific antiserum directed against the amino-terminus of p68c-ets-1, which is highly hydrophobic by contrast to the hydrophilic NH2 terminus of p54c ets-1. This antiserum specifically immunoprecipitated p68c-ets-1 and P135gag-myb ets only in denaturing and reducing conditions. Despite these biochemical differences at their amino-terminal parts, p68c-ets-1, as p54c-ets-1, is a nuclear protein able to bind to DNA in vitro. Unlike p54c-ets-1 which is expressed at high levels in T- and B-lymphoid cells, p68c-ets-1 is not expressed in lymphoid cells of the spleen. Thus, the two c-ets-1 encoded proteins, although both exhibiting DNA-binding properties in vitro, display differences both in the nature of their specific NH2 termini, and in their level and pattern of expression. PMID- 2204020 TI - Cloning, sequencing, and expression of mouse c-ets-1 cDNA in baculovirus expression system. AB - The protooncogene c-ets-1 is preferentially expressed in lymphoid cells. The protein product of this gene has been found to be a phosphorylated nuclear protein. When lymphocytes are stimulated with calcium ionophore, hyperphosphorylation of c-ets-1 occurs. In order to study the biological and biochemical functions of the c-ets-1 protein in detail, it is important to prepare adequate quantity of the c-ets-1 protein. To this end, we have cloned, sequenced, and expressed mouse c-ets-1 cDNA in baculovirus expression vector. Sequence analysis indicated that mouse c-ets-1 cDNA codes for a 50/51-kd protein. Since the mouse c-ets-1 protein in mouse lymphocytes is a 60/62-kd protein, the result obtained indicated that the c-ets-1 protein undergoes posttranslational modification by phosphorylation. When the c-ets-1 cDNA was expressed in the baculovirus expression vector, insect cells infected with a recombinant virus synthesizes a protein of the same size but with 50-100 times more of the c-ets-1 protein than that of mouse lymphocytes. The Staphylococcus aureus V8 protease mapping analysis of mouse c-ets-1 proteins synthesized in mouse and insect cells showed that they are identical. Thus, the c-ets-1 protein synthesized in insect cells will allow us to purify and study the functions of the c-ets-1 protein in detail. PMID- 2204019 TI - Target dependence of antisense oligodeoxynucleotide inhibition of c-Ha-ras p21 expression and focus formation in T24-transformed NIH3T3 cells. AB - The relationship of antisense oligodeoxynucleotide inhibition to the predicted secondary structure of human c-Ha-ras oncogene mRNA was examined. Three antisense pentadecade-oxynucleotides complementary to the 5' cap region, a predicted loop in the 5' untranslated region, and the initiation codon region of c-Ha-ras mRNA were synthesized. T24-transformed NIH3T3 cells were treated for 24 hr with each anti-ras oligomer or control sequence. The levels of c-Ha-ras p21 antigen were then analyzed by radioimmunoprecipitation. Inhibition of p21 expression was sequence-specific and dose-dependent. The efficacy of the cap sequence in reducing p21 expression was greater than that of the initiation codon target, which in turn was more effective than the target upstream of the initiation codon. Antisense inhibition of p21 expression correlated with inhibition of focus formation. PMID- 2204021 TI - Stimulation of renal and hepatic c-myc and c-Ha-ras expression by unilateral nephrectomy. AB - Unilateral nephrectomy induces compensatory hypertrophy of the contralateral kidney in rats, resulting in a 25% weight increase in 14 days. We have demonstrated that expression of the c-myc and c-Ha-ras protooncogenes is increased more than ten-fold in the contralateral kidney within 4 to 8 hr following unilateral nephrectomy in rats. The increased expression of these genes is analogous to the increased expression of c-myc and c-Ha-ras that occurs early in liver regeneration, preceding the first increase in DNA synthesis by at least 20 hr. In order to define the tissue specificity of the signals for compensatory renal hypertrophy, we also determined the early protooncogene response and the proliferative response in the liver of rats following unilateral nephrectomy. The expression of c-myc and c-Ha-ras was also increased (five- to ten-fold) in the livers of these animals. DNA synthesis was stimulated in the contralateral kidney at 26-30 hr following nephrectomy as measured by 3H thymidine incorporation, indicating a hyperplastic response to unilateral nephrectomy. However, there was no increase in DNA synthesis in the liver despite the dramatic increase in c-myc and c-Ha-ras expression. Our data suggest that the early increase in protooncogene expression in response to unilateral nephrectomy is stimulated by circulating signals that are not tissue-specific. Increased protooncogene expression in both kidney and liver following unilateral nephrectomy is an early response to the regenerative stimulus, but later signals must provide the tissue specificity necessary for regeneration and cellular proliferation. PMID- 2204022 TI - The beta-interferon-mediated antimitogenic state resembles the anti-viral state. AB - Much controversy regarding the effect of interferons in control of the animal cell cycle can be reconciled by acknowledging that, until recently, few laboratories enjoyed access to both pure interferons and pure growth-factor preparations. Using such reagents, we show data that suggest that antimitogenic state in Balb/c-3T3 cells by beta-interferon resembles the antiviral state in two important regards: dosage and kinetics. Picomolar concentrations of homogeneous beta-interferon inhibit the mitogenic response to recombinant platelet-derived growth-factor B chain homodimer. The antimitogenic response is seen only when cells are exposed to pure beta-interferon for an extended time prior to platelet derived growth-factor treatment. The interferon-mediated antimitogenic state is exerted at some point in the cell cycle subsequent to c-myc gene induction. PMID- 2204023 TI - ["Pediatriia" journal in 1989]. PMID- 2204024 TI - [Complex assessment of sexual development of pubertal girls with diabetes mellitus]. AB - Abnormal sexual development of girls suffering from diabetes mellitus was shown to depend on the diabetes gravity and degree of its compensation. The patients with a history of multiple diabetic comas were characterized by dramatic retardation of sexual development. In view of this fact it is assumed that deep disorders of metabolism may influence the central brain structures responsible for reproductive function. PMID- 2204025 TI - [Doppler ultrasonics in current perinatology]. PMID- 2204026 TI - Cloning and nucleotide sequence of the genes coding for the Sau96I restriction and modification enzymes. AB - The genes coding for the GGNCC specific Sau96I restriction and modification enzymes were cloned and expressed in E. coli. The DNA sequence predicts a 430 amino acid protein (Mr: 49,252) for the methyltransferase and a 261 amino acid protein (Mr: 30,486) for the endonuclease. No protein sequence similarity was detected between the Sau96I methyltransferase and endonuclease. The methyltransferase contains the sequence elements characteristic for m5C methyltransferases. In addition to this, M.Sau96I shows similarity, also in the variable region, with one m5C-methyltransferase (M.SinI) which has closely related recognition specificity (GGA/TCC). M.Sau96I methylates the internal cytosine within the GGNCC recognition sequence. The Sau96I endonuclease appears to act as a monomer. PMID- 2204027 TI - Transcript levels of the Saccharomyes cerevisiae DNA repair gene RAD23 increase in response to UV light and in meiosis but remain constant in the mitotic cell cycle. AB - The RAD23 gene of Saccharomyces cerevisiae is required for excision-repair of UV damaged DNA. In this paper, we determine the location of the RAD23 gene in a cloned DNA fragment, identify the 1.6 kb RAD23 transcript, and examine RAD23 transcript levels in UV damaged cells, during the mitotic cell cycle, and in meiosis. The RAD23 mRNA levels are elevated 5-fold between 30 to 60 min after 37 J/m2 of UV light. RAD23 mRNA levels rise over 6-fold during meiosis at a stage coincident with high levels of genetic recombination. This response is specific to sporulation competent MATa/MAT alpha diploid cells, and is not observed in asporogenous MATa/MATa diploids. RAD23 mRNA levels, however, remain constant during the mitotic cell cycle. PMID- 2204028 TI - A yeast homolog of the human UEF stimulates transcription from the adenovirus 2 major late promoter in yeast and in mammalian cell-free systems. AB - We report the identification and purification of a yeast factor functionally homologous to the human upstream element factor (UEFh). Although the yeast protein (UEFy) has a higher molecular weight than the HeLa UEF (60 kD versus 45 kD) both have identical DNA-binding properties: the purified UEFy recognizes the Adenovirus 2 (Ad2) major late promoter upstream element (MLP-UE; from nucleotide 49 to -67) as well as the IVa2 upstream element (IVa2-UE; from nucleotide -98 to 122) with a higher affinity for the MLP-UE than for the IVa2-UE. Based on its DNA binding specificity, size and thermostability, the UEFy protein appears also similar or equivalent to the centromere binding protein CP1. In a competition assay with oligonucleotides containing the MLP-UE binding site, a drastic reduction of Ad2 MLP transcription was observed both in a HeLa and in a yeast cell free system, which was restored by addition of either the purified UEFh or UEFy proteins. We conclude that both UEFh and UEFy activate transcription from the Ad2 MLP upon binding to the upstream element, whatever is the in vitro cell free system (yeast or HeLa). This indicate that some regulatory function represented by the upstream element and its cognate factor, is well conserved between human and yeast. PMID- 2204029 TI - Characterization of unr; a gene closely linked to N-ras. AB - The mammalian N-ras gene is believed to play a role in cellular proliferation, differentiation, and transformation. While investigating N-ras, we isolated cDNA's that originate from a closely linked upstream gene. RNase protection assays reveal that this gene, unr, is transcribed in the same direction as N-ras and that its 3' end is located just 130 base pairs away from the point at which N ras transcription begins. The close spatial relationship between the two genes is conserved in all species from which the N-ras gene has been isolated. An open reading frame, potentially encoding a 798 amino acid protein, is contained within the unr cDNA. Neither the primary protein structure nor the nucleic acid sequence of unr is homologous to any other known gene, including N-ras. Unr transcripts are detected in mouse, rat and human cells, and Southern analysis indicates that the unr locus found immediately upstream of the N-ras gene is transcriptionaly active in the mouse since only a single copy of unr is detected in this species. Unr produces multiple transcripts that differ in their 3' ends and are apparently created through the differential use of multiple polyadenylation sites located in the 3' untranslated region of the gene. Both unr and N-ras are expressed in all tissues examined. In the testis, both genes are developmentally regulated, with an increase in expression occurring upon testicular maturation. Thus the two genes may be coordinately regulated, at least in certain circumstances. Our findings suggest that a thorough analysis of the relationship that exists between the two genes could potentially provide insights into the regulation and/or function of N-ras. PMID- 2204030 TI - The gene for cyclophilin (peptidyl-prolyl cis-trans isomerase) from Schizosaccharomyces pombe. PMID- 2204031 TI - Nucleotide sequence of Clostridium botulinum C1 neurotoxin. PMID- 2204032 TI - Nucleotide sequence of the chloroplast gene for the 4 kD K polypeptide of photosystem II (psbK) and the psbK-tufA intergenic region of Chlamydomonas reinhardtii. PMID- 2204033 TI - Nucleotide sequence and deduced amino acid sequence of Mycobacterium leprae gene showing homology to bacterial atp operon. PMID- 2204034 TI - Nucleotide sequence of the fadA and fadB genes from Escherichia coli. PMID- 2204035 TI - A simple method for the preparation of chromosomal DNA from cell culture. PMID- 2204036 TI - Rapid isolation of miniprep DNA for double strand sequencing. PMID- 2204037 TI - A rapid method of preparing megabase plant DNA. PMID- 2204038 TI - Comparing antibiotics in postoperative infection. PMID- 2204040 TI - When London burned. PMID- 2204039 TI - Full circle. Interview by Joanna Trevelyan. PMID- 2204041 TI - [Lingual retention abutment for Class I and II R.P.D]. PMID- 2204042 TI - Complex fractures of the metatarsals. PMID- 2204043 TI - Progressive diaphyseal dysplasia: case report and literature review. AB - We describe a case of progressive diaphyseal dysplasia occurring sporadically in a 25-year-old woman. This patient had menorrhagia, and severe anemia and hepatosplenomegaly, unusual clinical features of this disease. PMID- 2204044 TI - [Use of ultrasonic scalers]. PMID- 2204045 TI - [Disinfection of toothbrushes. Experimental research]. AB - Aim of the present paper is to verify in a vitro study, the possible disinfection of the toothbrushes with an UV instrument (Dentec 4000). The modifications in microbic concentration after a contamination with microbial suspension of oral cavity have been estimated. PMID- 2204046 TI - [High speed aspiration]. PMID- 2204047 TI - [Use of the curette and root planing]. PMID- 2204048 TI - [Biological basis of fluoride resistance]. AB - The authors synthetically illustrate some fundamental concepts about the mechanisms through which the oral flora develops fluoride resistance and the main consequences of this phenomenon at a biochemical and microbiological level. They briefly discuss the most recent experimental contributes of the literature in this field. PMID- 2204050 TI - The neurotoxicity of MPTP and the relevance to Parkinson's disease. PMID- 2204049 TI - Crystallographic consequences of molecular dissymmetry. AB - The molecular chirality associated with an optically active molecule is manifested in the bulk crystallography of the compound. The historical development of optical activity was greatly aided by systematic studies of the habits of enantiomorphic crystals. The concepts of molecular dissymmetry, crystallography, and chirality are therefore linked. Racemic materials can be characterized by means of their melting-point phase diagrams, and this information used to design rational separations of racemic mixtures into their component enantiomers. Certain compounds are found to resolve spontaneously upon crystallization, and the enantiomers of these conglomerate species may be separated by direct crystallization. Compounds which crystallize as true racemates require resolution through the formation and separation of dissociable diastereomer species. The choice of resolution pathway is therefore determinable through an evaluation of the melting-point phase diagrams. When possible, resolution through direct crystallization represents the simplest, most cost effective means of enantiomer resolution. PMID- 2204051 TI - [An analysis of the interrelationship of the HLA genotype and carbohydrate metabolism in the families of probands with insulin-dependent diabetes mellitus]. AB - A total of 15 families were investigated: probands with insulin-dependent diabetes mellitus and their relatives of the 1st degree of progeny (43 persons) in order to study the distribution of HLA antigens and their interrelationship with the gravity of a course of diabetes mellitus and the type of GTT. Antigens DR3 and/or DR4 were revealed in 93% of probands, especially in heterozygous patients (57.1%). A low level of C-peptide (0.21 +/- 0.03 ng/ml) was noted in most of the probands excluding 3 patients with nephropathy. Distinct relationship of antigens DR3 and DR4 with a clinical course of disease and its severity was undetectable. Antigens DR3 or/and DR4 were detected in 96% of the relatives with the prevalence of antigen DR4 (in 54.2%). During GTT normal tolerance was observed in 82.1% (23 persons), disorders were noted in 4, insulin-dependent diabetes mellitus--in one. Most of the relatives (82.6%) with normal glucose tolerance had antigens DR3 and/or DR4. Irrespective of the type of DR antigens the probands' relatives were characterized by moderate hyperinsulinism (by the results of IRI and C-peptide of blood serum). PMID- 2204052 TI - [The effect of luliberin and sulpiride on the secretion of gonadotropic hormones and prolactin in patients with obesity]. AB - The role of dopamine (DA) in the secretion of gonadotropic hormones was studied in women with obesity and normal body mass. Tests with sulpiride (peripheral antagonist of DA-receptors), sulpiride LH-RH and thyroliberin were made. Basal and LH-RH-stimulated secretion of gonadotropins and prolactin (PRL) was studied to reveal the relationship of their secretion with the status of the hypothalamohypophyseal system. It was shown that the blockade of peripheral DA receptors did not result in an increase in the basal and LH-RH-stimulated secretion of LH either in healthy women or in women with obesity at the normal basal level of gonadotropic hormones. Hyperprolactinemia caused by sulpiride or LH-RH, did not lower LH secretion during the entire period of investigation. There were no differences either in the basal level of gonadotropic hormones or in their ejection in response to LH-RH administration in women with normal and excess body mass. Stimulation of PRL secretion in response to LH-RH was found in patients with exogenous-constitutional obesity and minimum signs of diencephalic pathology. Slight inhibition of PRL secretion after LH-RH administration was noted in women with obesity of hypothalamic type and unstable type of disorder of EEG. The absence of changes in PRL secretion was noted in women with strongly marked hypothalamic signs of the disease. PMID- 2204053 TI - [Nontraditional methods in the combined treatment of diabetes mellitus]. PMID- 2204054 TI - [Kidney tubular function in diabetes mellitus]. PMID- 2204055 TI - [A.I. Togunova--a pioneer in antituberculosis BCG vaccination in the USSR]. PMID- 2204057 TI - Diastereomer-dependent substrate reduction properties of a dinitrogenase containing 1-fluorohomocitrate in the iron-molybdenum cofactor. AB - In vitro synthesis of the iron-molybdenum cofactor (FeMo-co) of dinitrogenase using homocitrate and its analogs allows the formation of modified forms of FeMo co that show altered substrate specificities (N2, acetylene, cyanide, or proton reduction) of nitrogenase [reduced ferredoxin:dinitrogen oxidoreductase (ATP hydrolyzing), EC 1.18.6.1]. The (1R,2S)-threo- and (1S,2S)-erythro-fluorinated diastereomers of homocitrate have been incorporated in vitro into dinitrogenase in place of homocitrate. Dinitrogenase activated with FeMo-co synthesized using threo-fluorohomocitrate reduces protons, cyanide, and acetylene but cannot reduce N2. In addition, proton reduction is inhibited by carbon monoxide (CO), a characteristic of dinitrogenase from NifV- mutants. Dinitrogenase activated with FeMo-co synthesized using erythro-fluorohomocitrate reduces protons, cyanide, acetylene, and N2. In this case proton reduction is not inhibited by CO, a characteristic of the wild-type enzyme. Cyanide reduction properties of dinitrogenase activated with FeMo-co containing either fluorohomocitrate diastereomer are similar, and CO strongly inhibits cyanide reduction. Dinitrogenases activated with FeMo-co containing homocitrate analogs with a hydroxyl group on the C-1 position are much less susceptible to CO inhibition of cyanide reduction. However, proton and cyanide reduction by dinitrogenase containing FeMo-co activated with (1R,2S) threo-isocitrate is only one-third that of dinitrogenase activated with the racemic mixture of -isocitrate and shows strong CO inhibition of substrate reduction. These results suggest that CO inhibition of proton and cyanide reduction occurs when the hydroxyl group on the C-1 position of analogs is "trans" to the C-2 carboxyl group (i.e., in the threo conformation). When racemic mixtures of these analogs are used in the system, it seems that the erythro form is preferentially incorporated into dinitrogenase. Finally, carbonyl sulfide inhibition of substrate reduction by dinitrogenase is dependent on the homocitrate analog incorporated into FeMo-co. PMID- 2204056 TI - Reduced expression of the liver/beta-cell glucose transporter isoform in glucose insensitive pancreatic beta cells of diabetic rats. AB - Rats injected with a single dose of streptozocin at 2 days of age develop non insulin-dependent diabetes 6 weeks later. The pancreatic beta islet cells of these diabetic rats display a loss of glucose-induced insulin secretion while maintaining sensitivity to other secretagogues such as arginine. We analyzed the level of expression of the liver/beta-cell glucose transporter isoform in diabetic islets by immunofluorescence staining of pancreas sections and by Western blotting of islet lysates. Islets from diabetic animals have a reduced expression of this beta-cell-specific glucose transporter isoform and the extent of reduction is correlated with the severity of hyperglycemia. In contrast, expression of this transporter isoform in liver is minimally modified by the diabetes. Thus a decreased expression of the liver/beta-cell glucose transporter isoform in beta cells is associated with the impaired glucose sensing characteristic of diabetic islets; our data suggest that this glucose transporter may be part of the beta-cell glucose sensor. PMID- 2204058 TI - Inter- and intraspecies spread of Escherichia coli in a farm environment in the absence of antibiotic usage. AB - The spread of wild-type Escherichia coli bearing a transferable plasmid was studied in a farm environment. E. coli of bovine and porcine origin were marked by resistance to nalidixic acid (Nar) or rifampicin (Rfr), and a transferable, multiple resistance plasmid (pSL222-1 derivative of plasmid R222) was introduced by conjugation. In separate experiments, the two mutant derivatives were fed back to the respective host animals, which were housed adjacent to, but separate from, one or more "recipient" animals. No antibiotic was given. Although the Rfr derivatives declined rapidly to undetectable levels within 1 week, the Nar mutants of bovine and porcine origin persisted in the original hosts and in their bedding throughout most of each 4-month test period. Test bacteria were isolated from mice residing in the same pen as the donor animals and from multiple secondary hosts having direct or indirect contact with the inoculated donors, but not from neighboring animals maintained in isolation. The bovine mutant was excreted by two caretakers for greater than 4 weeks and was recovered for 4-6 weeks from pigs, fowl, and flies. Although the porcine mutant appeared to colonize less effectively, it spread rapidly to flies and mice and was recovered transiently from humans and fowl. Despite high transfer rates of plasmid pSL222-1 from E. coli K-12 in vitro, transfer of the plasmid from the animal E. coli host was very low and transfer in vivo was not detected among indigenous gut or environmental bacteria. E. coli of animal origin can spread rapidly and can colonize the intestinal tract of humans and of other animals in the absence of antibiotic selection. PMID- 2204059 TI - Cloning by function: an alternative approach for identifying yeast homologs of genes from other organisms. AB - Studies of cell physiology and structure have identified many intriguing proteins that could be analyzed for function by using the power of yeast genetics. Unfortunately, identifying the homologous yeast gene with the two most commonly used approaches--DNA hybridization and antibody cross-reaction--is often difficult. We describe a strategy to identify yeast homologs based on protein function itself. This cloning-by-function strategy involves first identifying a yeast mutant that depends on a plasmid expressing a cloned foreign gene. The corresponding yeast gene is then cloned by complementation of the mutant defect. To detect plasmid dependence, the colony color assay of Koshland et al. [Koshland, D., Kent, J. C. & Hartwell, L. H. (1985) Cell 40, 393-403] is used. In this paper, we test the feasibility of this approach using the well-characterized system of DNA topoisomerase II in yeast. We show that (i) plasmid dependence is easily recognized; (ii) the screen efficiently isolates mutations in the desired gene; and (iii) the wild-type yeast homolog of the gene can be cloned by screening for reversal of the plasmid-dependent phenotype. We conclude that cloning by function can be used to isolate the yeast homologs of essential genes identified in other organisms. PMID- 2204060 TI - Structure-based design of nonpeptide inhibitors specific for the human immunodeficiency virus 1 protease. AB - By using a structure-based computer-assisted search, we have found a butyrophenone derivative that is a selective inhibitor of the human immunodeficiency virus 1 (HIV-1) protease. The computer program creates a negative image of the active site cavity using the crystal structure of the HIV-1 protease. This image was compared for steric complementarity with 10,000 molecules of the Cambridge Crystallographic Database. One of the most interesting candidates identified was bromperidol. Haloperidol, a closely related compound and known antipsychotic agent, was chosen for testing. Haloperidol inhibits the HIV-1 and HIV-2 proteases in a concentration-dependent fashion with a Ki of approximately 100 microM. It is highly selective, having little inhibitory effect on pepsin activity and no effect on renin at concentrations as high as 5 mM. The hydroxy derivative of haloperidol has a similar effect on HIV-1 protease but a lower potency against the HIV-2 enzyme. Both haloperidol and its hydroxy derivative showed activity against maturation of viral polypeptides in a cell assay system. Although this discovery holds promise for the generation of nonpeptide protease inhibitors, we caution that the serum concentrations of haloperidol in normal use as an antipsychotic agent are less than 10 ng/ml (0.03 microM). Thus, concentrations required to inhibit the HIV-1 protease are greater than 1000 times higher than the concentrations normally used. Haloperidol is highly toxic at elevated doses and can be life-threatening. Haloperidol is not useful as a treatment for AIDS but may be a useful lead compound for the development of an antiviral pharmaceutical. PMID- 2204061 TI - Induction of a chronic myelogenous leukemia-like syndrome in mice with v-abl and BCR/ABL. AB - The v-abl gene in Abelson virus induces pre-B-cell lymphoma in mice while the BCR/ABL oncogene is associated with chronic myelogenous leukemia and some cases of acute lymphocytic leukemia in humans. Understanding the mechanisms by which these oncogenes affect various cell types has been hampered by a paucity of experimental systems that reproduce the range of biological effects associated with them. We have developed an experimental system in which murine hematopoietic stem cell populations are infected with either v-abl or BCR/ABL retroviruses and are used to reconstitute lethally irradiated mice. Irrespective of the form of activated abl, greater than 90% of the animals reconstituted with such cells develop tumors. About 50% of them develop a myeloproliferative syndrome that shares several features with the chronic phase of chronic myelogenous leukemia; the remaining animals succumb to pre-B-cell lymphomas. The myeloproliferative syndrome is characterized by large numbers of clonally derived, infected myeloid cells. This model will allow study of the mechanism by which activated abl genes affect hematopoietic precursors in chronic myelogenous leukemia. Furthermore, our results demonstrate that introduction of an activated abl gene into the appropriate target cell, not the structure of the gene, is the major determinant in myeloid cell specificity. PMID- 2204062 TI - Substrate specificity of trypsin investigated by using a genetic selection. AB - The structural determinants of the primary substrate specificity of rat anionic trypsin were examined by using oligonucleotide-directed mutagenesis coupled to a genetic selection. A library was created that encoded trypsins substituted at amino acid positions 189 and 190 at the base of the substrate binding pocket. A genetic selection, with a dynamic range of 5 orders of proteolytic activity, was used to search 90,000 transformants of the library. Rapid screening for arginyl amidolysis and esterolysis confirmed the activity of the purified isolates. Trypsin and 15 mutant trypsins with partially preserved function were identified and characterized kinetically on arginyl and lysyl peptide substrates. Alternative arrangements of amino acids in the substrate binding pocket sustained efficient catalysis. A negative charge at amino acid position 189 or 190 was shown to be essential for high-level catalysis. With the favored aspartic acid residue at position 189, several amino acids could replace serine at position 190. Modulation of the specificity for arginine and lysine substrates was shown to depend on the amino acid at position 190. The regulatory effect of the amino acid side chain at position 190 on the substrate specificity is also reflected in substrate binding pockets of naturally occurring trypsin homologs. PMID- 2204063 TI - Human DNA ligase I cDNA: cloning and functional expression in Saccharomyces cerevisiae. AB - Human cDNA clones encoding the major DNA ligase activity in proliferating cells, DNA ligase I, were isolated by two independent methods. In one approach, a human cDNA library was screened by hybridization with oligonucleotides deduced from partial amino acid sequence of purified bovine DNA ligase I. In an alternative approach, a human cDNA library was screened for functional expression of a polypeptide able to complement a cdc9 temperature-sensitive DNA ligase mutant of Saccharomyces cerevisiae. The sequence of an apparently full-length cDNA encodes a 102-kDa protein, indistinguishable in size from authentic human DNA ligase I. The deduced amino acid sequence of the human DNA ligase I cDNA is 40% homologous to the smaller DNA ligases of S. cerevisiae and Schizosaccharomyces pombe, homology being confined to the carboxyl-terminal regions of the respective proteins. Hybridization between the cloned sequences and mRNA and genomic DNA indicates that the human enzyme is transcribed from a single-copy gene on chromosome 19. PMID- 2204064 TI - Cytoplasmic expression system based on constitutive synthesis of bacteriophage T7 RNA polymerase in mammalian cells. AB - A mouse cell line that constitutively synthesizes the bacteriophage T7 RNA polymerase was constructed. Fluorescence microscopy indicated that the T7 RNA polymerase was present in the cytoplasmic compartment. The system provided, therefore, a unique opportunity to study structural elements of mRNA that affect stability and translation. The in vivo activity of the bacteriophage polymerase was demonstrated by transfection of a plasmid containing the chloramphenicol acetyltransferase (CAT) gene flanked by T7 promoter and termination signals. Synthesis of CAT was dependent on the presence of a cDNA copy of the untranslated region of encephalomyocarditis virus (ECMV) RNA downstream of the T7 promoter, consistent with the absence of RNA-capping activity in the cytoplasm. CAT expression from a plasmid, pT7EMCAT, containing the T7 and EMCV regulatory elements was detected within 4 hr after transfection and increased during the next 20 hr, exceeding that obtained by transfection of a plasmid with the CAT gene attached to a retrovirus promoter and enhancer. Nevertheless, the presumably cap-independent transient expression of CAT from pT7EMCAT was increased more than 500-fold when the transfected cells also were infected with wild-type vaccinia virus. A protocol for high-level expression involved the infection of the T7 RNA polymerase cell line with a single recombinant vaccinia virus containing the target gene regulated by a T7 promoter and EMCV untranslated region. PMID- 2204065 TI - Cloning and cDNA sequence of a bovine submaxillary gland mucin-like protein containing two distinct domains. AB - A lambda gt11 cDNA library prepared from bovine submaxillary gland mRNA was screened with polyclonal anti-apo-bovine submaxillary mucin antibodies with the aim of obtaining the deduced amino acid sequence of the mucin core protein. One of the positive clones had a 1.8 kilobase (kb) cDNA insert and coded for an incomplete protein. A 2.0-kb cDNA clone was isolated by rescreening the library with the 1.8-kb cDNA. Nucleotide sequencing of the full-length 2.0-kb cDNA revealed an open reading frame that coded for a 563-amino acid protein. A striking feature of the cloned protein is the skewed distribution of the amino acids, most notably that of the hydroxy amino acids and cysteine. The amino terminal domain of 339 residues is very rich in threonine, serine, and glycine and poor in cysteine, aspartic acid, tyrosine, phenylalanine, and tryptophan. In contrast, the carboxyl-terminal domain of 224 residues is rich in cysteine, aspartic acid, tyrosine, lysine, and asparagine and relatively poor in threonine, serine, and glycine. A search of the protein data bank for homologies to the deduced amino acid sequence revealed statistically significant matches to several proteins, including the porcine submaxillary apomucin fragment. The cysteine-rich domain by itself was not statistically homologous with any of the registered polypeptide sequences. RNA blot analysis using DNA probes corresponding to the mucin-like and cysteine-rich regions detected a nearly identical pattern of transcripts, demonstrating that the characterized clones are not artifacts of cDNA library construction. The blots also showed the presence of polydisperse transcripts in bovine submaxillary gland but no detectable hybridization signals in liver or brain RNA. PMID- 2204066 TI - Purification to homogeneity and partial characterization of cytotoxic lymphocyte maturation factor from human B-lymphoblastoid cells. AB - A cytokine that can synergize with interleukin 2 to activate cytotoxic lymphocytes was purified to homogeneity. The protein, provisionally called cytotoxic lymphocyte maturation factor (CLMF), was isolated from a human B lymphoblastoid cell line that was induced to secrete lymphokines by culture with phorbol ester and calcium ionophore. The purification method, utilizing classical and high-performance liquid chromatographic techniques, yielded protein with a specific activity of 8.5 x 10(7) units/mg in a T-cell growth factor assay. Analysis of the purified protein by sodium dodecyl sulfate/polyacrylamide gel electrophoresis demonstrated that CLMF is a 75-kDa heterodimer composed of disulfide-bonded 40-kDa and 35-kDa subunits. Determination of the N-terminal amino acid sequences of the two subunits revealed that both subunits are not related to any previously identified cytokine. Purified CLMF stimulated the proliferation of human phytohemagglutinin-activated lymphoblasts by itself and exerted additive effects when used in combination with suboptimal amounts of interleukin 2. Furthermore, the purified protein was shown to synergize with low concentrations of interleukin 2 in causing the induction of lymphokine-activated killer cells. PMID- 2204068 TI - Multiple sclerosis--the unpredictable enemy. PMID- 2204069 TI - Granuflex dressings in treatment of full thickness pressure sores. AB - Granuflex Paste and Granuflex E extend the range of indications for using Granuflex products in pressure sore therapy. These dressings enable ulcers of any degree of severity to be treated, although they perform better on sores on limbs than on sacral sores. PMID- 2204067 TI - An inositol 1,4,5-trisphosphate-sensitive Ca2+ pool in liver nuclei. AB - Recent studies in our laboratory have revealed the existence of an ATP- and calmodulin-dependent Ca2+ uptake system in rat liver nuclei that can promote increases in the free Ca2+ concentration in the nuclear matrix. In the present investigation we show that liver nuclei possess a marked ability to sequester and buffer Ca2+, suggesting a potential role for the nucleus in the regulation of the cytosolic free Ca2+ concentration. In addition, we demonstrate that the intracellular messenger, inositol 1,4,5-trisphosphate [Ins-(1,4,5)P3], stimulates the release of a fraction of the nuclear Ca2+ and transiently lowers the intranuclear free Ca2+ concentration. The Ins(1,4,5)P3-stimulated Ca2+ release is followed by Ca2+ reuptake into an inositol phosphate-insensitive nuclear compartment. Together, these results demonstrate that liver nuclei contain, at least, two Ca2+ pools, one of which is releasable by Ins(1,4,5)P3. These findings are consistent with a role for the nucleus in the modulation of the cytosolic free Ca2+ level by agonists and suggest that the control of the nuclear Ca2+ load by second messengers may participate in the regulation of intranuclear Ca2(+) dependent processes by hormones and other agents. PMID- 2204070 TI - Triterpenoid saponins. Part 6. PMID- 2204071 TI - [The development of pharmacy in German universities in the 19th century]. AB - This article analyses the development of pharmacy as an academic discipline in Greifswald, Gottingen, Ingolstadt-Landshut-Munchen, Breslau and Marburg. The research shows that the establishing of independent institutes of pharmacy under competent leadership (for instance Ernst Schmidt in Marburg) played a decisive role in developing the discipline pharmacy. PMID- 2204072 TI - Maternal hormone manipulations and the development of obesity in rats. AB - Pregnant rats were injected with either insulin, corticosterone, thyroxin, or saline during the third trimester (week) of pregnancy. Offspring from these groups had equivalent body weights at birth and at weaning. However, beginning at approximately seven weeks of age, male offspring in the insulin condition gained weight at significantly higher rates than their counterparts in the other three conditions. This increase in body weight was accompanied by a significant increase in carcass lipid content. These effects were not observed in female offspring. PMID- 2204073 TI - Sleep, brain activation and cognition. AB - Some data have shown the presence of time-of-day effects in learning processes. We explore here whether the same phenomenon occurs during the night and how it relates to REM sleep. In an initial approach to the question, this paper points out the relationships between: 1) REM sleep and brain activation, and 2) REM sleep and information processing. The data are discussed in terms of a REM sleep implication on information processing and we examine the possibility of modifying this processing by acting on REM sleep. PMID- 2204074 TI - [Accessory root on lateral upper incisor--case report of rare anomaly]. PMID- 2204075 TI - [Prosthetic treatment of badly atrophied mandible]. PMID- 2204077 TI - [Indirect bonding after set-up]. PMID- 2204076 TI - [Invisible crown margins--an in vitro study]. PMID- 2204078 TI - [Sharpening periodontal instruments with help of Periostar precision sharpening system]. PMID- 2204079 TI - [Implantation today--current status of implantation from clinical point of view (2). Problem of soft tissue integration]. PMID- 2204080 TI - [Mid- and soft-laser therapy--significant or nonsense?]. PMID- 2204081 TI - [Dentinogenesis imperfecta--case report]. PMID- 2204082 TI - [Effects of smoking and/or vitamin C on sulcular fluid rate in clinically healthy gingiva]. PMID- 2204083 TI - [Mandibular resection of 1812 of Baron Dupuytren. Was it the first?]. PMID- 2204084 TI - [Cast adhesive occlusal elements for correction of posterior open bite]. PMID- 2204085 TI - [Rational measurement technic for determining placement of upper anterior teeth in complete denture]. PMID- 2204086 TI - [Magnetic anchor in corrosion test]. PMID- 2204088 TI - [Application of activated carbon to radiochemical analysis--adsorption behavior of inorganic ions]. PMID- 2204087 TI - [Dimensional accuracy of partially edentulous arch in relation to impression material]. PMID- 2204089 TI - [Design and fabrication of a complete removable denture opposing a fixed denture. 1]. PMID- 2204090 TI - Are receptor-associated nuclear proteins associated with the earliest effects of steroid hormones? AB - The functional importance of the interaction of hsp90 with receptors for steroid hormones in the action of these hormones has been suggested. This hypothesis, although not yet proven, is supported by new data obtained in our laboratory and in those of others, whereas no conflicting experimental results have been presented. Our recent studies have dealt with the cloning of hsp90, transfection of normal and mutated receptors, the effects of the antihormone RU486 and immunohistochemistry. PMID- 2204091 TI - Regulation, clinical and biological significance of cathepsin D in breast cancer. AB - The lysosomal protease, pro-cathepsin D, is overexpressed and secreted by human breast cancers. In estrogen-responsive breast cancer cell lines, estrogens and growth factors stimulate cathepsin D expression through distinct mechanisms. Clinical studies indicate that high cathepsin D concentration in primary breast cancers is correlated with an increased risk of metastasis and particularly useful to orientate node-negative tumors towards an adjuvant therapy. PMID- 2204092 TI - Regulation of fatty acid synthetase by progesterone in normal and tumoral human mammary glands. AB - Progesterone and estrogens play an important role in the control of growth, differentiation and function of mammary epithelial cells. Their mechanism of action can be studied in human metastatic breast cancer cell lines (MCF7, T47D, ZR75-1...) that contain progesterone and estrogen receptors. We used this system to try to define progestin-regulated human genes which would permit to study progestin-regulation of gene expression in cell culture and to develop clinical markers of progestin-responsiveness. This paper summarizes our investigation of the progestin-regulated 250K protein, recently identified as human fatty acid synthetase (FAS). PMID- 2204093 TI - [Testosterone in saliva: application to the follow-up of prostate cancer]. AB - The basic aspects of steroid hormones transport, their tissular release and the interpretation of salivary testosterone values as a reflect of the free hormone in serum are reviewed in this article, as well as the salivary testosterone applications in several disorders, with a special emphasis on prostatic carcinoma. The usefulness of salivary testosterone in the short-term (n = 4) and long-term (n = 13) follow-up of patients affected by prostatic carcinoma after medical or surgical orchiectomy has also been studied. Our results show a correlation (r = 0.62) between salivary and serum concentration values, as well as a significative decrease (p less than 0.001) in both quantities after treatment. Both these findings and the advantages inherent to the sampling obtaining, lead to the conclusion that salivary testosterone is a good alternative to serum testosterone. PMID- 2204095 TI - Studies on steroid binding proteins in normal tissues and tumor cell lines. AB - Steroid binding proteins bind steroid hormones with high affinity and their function is to carry those hormones in the extracellular compartment. Since their discovery more than fifty years ago, many reports concerning their physicochemical structures and functions have contributed to the better understanding of those proteins. Recent advances in recombinant DNA technology have led to the availability of molecular probes for these proteins, and new approaches have been used to analyse their gene structures as well as the regulation of their synthesis. In the present report, we will review the new findings of the last five years which include the cloning and sequencing of the cDNAs and genes for corticosteroid binding globulin, testosterone estradiol binding globulin and androgen binding protein, as well as the tissue distribution and regulation of their mRNAs in normal tissues and cancer cell lines. PMID- 2204094 TI - [Hormone dependence in breast and prostate tumor cell lines]. AB - Knowledge about the role of sex hormones in the control of cell proliferation and cell-type specific protein synthesis is mainly collected by using cell culture techniques. The adoption of cell culture models addressed at defining these issues is due to the uncomplicated assessment of reliable proliferation-related parameters. Established cell lines derived from estrogen and androgen sensitive tissues, have been used in proliferation studies for more than thirty years. The data gathered so far can be summarized in three following working hypotheses: the direct and indirect-positive hypotheses and the indirect-negative hypothesis. Further characterization and assessment of the hormone dependence of growth factors and growth inhibitors will allow for the mechanistic understanding of the regulation of cell proliferation by sex hormones. PMID- 2204096 TI - Novel perspectives for structuring synthetic inhibitors of human blood platelet aggregation and potential antithrombotic agents. AB - An overview is presented on using molecular probes in tracing platelet function response patterns to specific structural features and physicochemical characteristics. Our carbamoylpiperidine nipecotoylpiperazine and related congeners are yielding new insights for as yet uncharted mechanisms of thrombocyte interaction dynamics, and the findings indicate promise for the development of novel potential antithrombotic agents. PMID- 2204097 TI - Use of attitude-behaviour models in exercise promotion. AB - Many studies have adopted a theoretical attitude-behaviour framework for the analysis of exercise behaviour. The most popular models include the Health Belief Model, the Protection Motivation Theory, the Social Cognitive Theory, the Theory of Reasoned Action, the Theory of Interpersonal Behaviour, and the Theory of Planned Behaviour. Aspects other than a preoccupation with health often have a strong influence upon an individual's decision whether or not to engage in exercise. Expectations of self-efficacy, attitudes towards exercising (the affective dimension), perceived barriers to exercise, and past behaviour exert strong influences upon behavioural intention, which in turn influences overt behaviour. In some instances, the variables explaining intention also exert a direct influence upon behaviour in parallel with their influence upon intention. Those promoting exercise behaviour should focus initial attention upon the habit of exercising rather than upon the development of traditional 'endurance fitness'. PMID- 2204098 TI - Ice hockey injuries. A review. AB - Ice hockey is a fast-paced game involving both finesse and controlled aggression. Injuries are related to direct trauma (80%) and overuse (20%), with high puck velocities, aggressive stick use, and body checking (collisions) accounting for most of these. A participant can anticipate an injury after playing 7 to 100 hours of hockey, depending on his age, and most injuries are caused during the actual game rather than during practice. Although facial injuries are common, they are decreasing because of adequate use of helmets and masks. Conversely, cervical spine injuries are being reported more frequently. Injuries to the upper extremity include acromioclavicular joint dislocations, scaphoid fractures, and 'gamekeeper's thumb.' Injuries to the lower extremity predominantly involve soft tissue, with strains of the hip adductor, tears of the medial collateral ligament of the knee, and contusions of the thigh are common. Scientific studies have reduced injury by providing improved protective equipment, stricter rules and their enforcement, and effective training and conditioning. PMID- 2204099 TI - Exercise and secondary amenorrhoea linked through endogenous opioids. PMID- 2204101 TI - Biomechanical factors affecting performance in netball. Implications for improving performance and injury reduction. AB - Despite netball having one of the largest number of participants of any team game within the Commonwealth there has been limited research conducted which biomechanically analysed skills of the game. However, information presented from biomechanical analyses of skills can provide coaches with the necessary theoretical basis to teach netball fundamentals to junior players. Biomechanical information can also be used to refine the existing techniques of experienced netball players so they may achieve optimal technical performance of game skills while minimising the potential for injury. Changes to footwork rules and to the material properties of court surfaces and footwear could reduce stress placed on the musculoskeletal system. However, the factor which influences musculoskeletal stress to the greatest extent is a player's landing technique. Thus, the first concern for all netball coaches must be to teach all players to land correctly. The magnitude and rate of loading of the high vertical and horizontal ground reaction forces generated when players execute abrupt landings in netball are reduced more effectively by encouraging players to throw higher passes, requiring the receiver to jump upward to catch the ball. However, to maximise the reduction in stress placed on the musculoskeletal system on landing, players should be encouraged to land with the foot neutrally aligned (not abducted or adducted), ensure adequate hip and knee flexion, and reduce the foot-hip displacement by eliminating an exaggerated 'striding out' position often adopted by netball players. Apart from landing techniques, the only netball skill that has been objectively analysed is goal shooting. To improve shooting accuracy players should demonstrate greater flexion of the knees and shooting elbow when preparing to shoot, sufficient but not excessive hyperextension of the hand to stabilise the ball, minimisation of trunk, arm and forearm movements during the shooting action in favour of increased hand motion, greater release height and greater release velocity. If the potential for injury from poorly executed skills in netball is to be minimised, further research is required to identify the most efficient methods of performing all skills involved in the game, including pivoting, rebounding, defensive movement patterns, and attacking movement strategies. PMID- 2204102 TI - [Apexification with calcium hydroxide]. PMID- 2204103 TI - Mesalazine (5-aminosalicylic acid) suppositories in the treatment of ulcerative proctitis or distal proctosigmoiditis. A randomized controlled trial. AB - A multicentre double-blind study was conducted to evaluate the efficacy and tolerability of 1 g or 1.5 g mesalazine daily compared with placebo in 94 patients with mild to moderate distal proctosigmoiditis (less than 20 cm). The study end point was the determination of clinical, endoscopic, and histologic remission rates at 4 weeks. Eleven patients, nine receiving placebo and two receiving 1.5 g mesalazine, withdrew during trial, mostly because of worsening of symptoms. At 4 weeks clinical remission was achieved in 7 of 31 (39%) patients with placebo, in 22 of 32 (69%) patients in the 1 g mesalazine group, and 23 of 31 (74%) patients in the 1.5 g mesalazine group. No serious clinical or biochemical side effect of treatment was reported. Mesalazine suppositories are safe, well tolerated, and very effective in patients with active distal proctosigmoiditis: 500 mg twice daily appears a suitable dose regimen. PMID- 2204100 TI - Impact of energy intake and exercise on resting metabolic rate. AB - Resting metabolic rate is modulated by the amount of calories consumed in the diet relative to energy expenditure. Excessive consumption of energy appears to increase resting metabolic rate while fasting and very low calorie dieting causes resting metabolic rate to decrease. Since the metabolic rate at rest is the primary component of daily energy expenditure, its reduction with caloric restriction makes it difficult for obese individuals to lose weight and to maintain weight that is lost. Whether exercise has a carry-over effect on resting metabolic rate remains controversial, even though this question has been studied extensively during the last 90 years. Reasons for contradictory results include variations in control of prior diet and exercise patterns, inadequate exercise frequency, intensity and duration, and the possibility of response to exercise varying between individuals. Several lines of evidence suggest exercise may modulate resting metabolic rate. Bed rest in sedentary individuals leads to a reduction in resting metabolic rate. Similarly, in highly trained runners, cessation of daily exercise training lowers resting metabolic rate by about 7 to 10%. Resting metabolic rate is depressed in previously sedentary obese individuals on a very low calorie diet, but it quickly returns to the predieting level when exercise of sufficient frequency, intensity and duration is undertaken while dieting. These findings suggest caloric intake and daily exercise can modulate resting metabolic rate. Exercise of adequate intensity and duration may also enhance resting metabolic rate. PMID- 2204104 TI - Reduced insulin secretion by subtotal pancreatectomy: preservation of insulin sensitivity and glucose tolerance in postoperative patients. AB - This study investigated insulin sensitivity and glucose tolerance after subtotal pancreatectomy for carcinoma of the head of the pancreas. Twelve consecutive, non diabetic patients were studied after potentially curative surgery at which the distal pancreas was stapled off, leaving approximately 15% of the pancreas in situ. Brief infusions of insulin (10 mU kg-1) and glucose (25 g) were given before and 4 days after operation. Postoperatively, blood glucose levels remained unchanged, whereas fasting levels of insulin. C-peptide, and pancreatic glucagon were decreased, although significantly (p less than 0.01) only for glucagon. The early and late phases of the insulin and C-peptide responses to glucose were severely reduced. Notably, the hypoglycemic action of insulin and the glucose tolerance were similar to those observed before operation. It is concluded that an acute reduction in pancreatic mass does not impair insulin action or glucose tolerance shortly after surgery. This contrasts with the insulin resistance and glucose intolerance seen shortly after pancreas-preserving intra-abdominal procedures of similar size. It is suggested that the decrease in glucagon levels is at least partly responsible for the preservation of insulin action after subtotal pancreatectomy. PMID- 2204105 TI - Myoelectric and manometric patterns of human rectosigmoid colon in irritable bowel syndrome and diverticulosis. AB - Rectosigmoid electric control activity and intraluminal pressure were measured in the fasting state and after a standard 3040-kJ meal in irritable bowel syndrome (IBS) patients (n = 41), diverticulosis patients (n = 15), and healthy controls (n = 13). Analysis of myoelectric and motor patterns was performed computer-based with home-made software. Spectral analysis (fast Fourier transform) and computer recognition of slow waves emulating visual scoring showed very similar slow-wave frequency patterns in all three groups. Calculation of contractile indices displayed a widely scattered variable of motility in all three groups without significant differences. IBS subgroups with different bowel patterns showed very similar frequencies of basic myoelectric rhythm and a considerable overlap of contractile activity without significant differences among the subgroups and compared with controls. Slow-wave rhythm seems unlikely to be the basis of disturbed motility in IBS and diverticular disease. A specific pattern of contractile activity was not detectable in either condition. PMID- 2204106 TI - [Chemical neuro-anatomy of the thalamus: an example of the co-expression of 2 neuropeptides, cholecystokinin and intestinal vasoactive peptide]. AB - Recent studies using hybridization histochemistry have demonstrated the presence of cholecystokinin (CCK) gene expression in thalamocortical and thalamo-striatal neurons. To further understand the chemical anatomy of the thalamus, we used the same method to study the coexpression of CCK and vasoactive intestinal peptide (VIP) genes in the same neurons. Most of the neurons expressing the VIP gene in the rat dorsal thalamus (found especially in the ventrolateral nucleus) also expressed the CCK gene, as demonstrated by autoradiography on emulsion-coated adjacent sections studied with probes recognizing either mRNA. Some further neurons, located in the reticular nucleus, had VIP mRNA at lower levels of expression but did not appear to contain CCK mRNA. PMID- 2204107 TI - [The DO2/VO2 relationship: and approach to cellular metabolism in "crisis" situations]. AB - The relationship between the organism's oxygen consumption (VO2) and its transport to the cells (DO2), termed the DO2/VO2 relationship, has been the subject of many publications during the past decade. The pathological changes occurring in this relationship in intensive care patients has been much studied, and certain conclusions drawn with regard to monitoring and therapeutic goals. After a brief review of the pathophysiological mechanisms involved we examine the practical implications of the DO2/VO2 concept, focusing on the many methodological and interpretation problems raised. PMID- 2204108 TI - Cell proliferation in carcinogenesis. AB - Chemicals that induce cancer at high doses in animal bioassays often fail to fit the traditional characterization of genotoxins. Many of these nongenotoxic compounds (such as sodium saccharin) have in common the property that they increase cell proliferation in the target organ. A biologically based, computerized description of carcinogenesis was used to show that the increase in cell proliferation can account for the carcinogenicity of nongenotoxic compounds. The carcinogenic dose-response relationship for genotoxic chemicals (such as 2 acetylaminofluorene) was also due in part to increased cell proliferation. Mechanistic information is required for determination of the existence of a threshold for the proliferative (and carcinogenic) response of nongenotoxic chemicals and the estimation of risk for human exposure. PMID- 2204110 TI - Electrostatic and steric contributions to regulation at the active site of isocitrate dehydrogenase. AB - The isocitrate dehydrogenase of Escherichia coli is regulated by covalent modification at the active site rather than, as expected, at an allosteric site. As a means of evaluating the mechanism of regulation, the kinetics of the substrate, 2R,3S-isocitrate, and a substrate analog, 2R-malate, were compared for the native, phosphorylated, and mutant enzymes. Phosphorylation decreases activity by more than a factor of 10(6) for the true substrate, but causes minor changes in the activity of the substrate analog. The kinetic results indicate that electrostatic repulsion and steric hindrance between the phosphoryl moiety and the gamma carboxyl group of 2R,3S-isocitrate are the major causes of the inactivation, with a lesser contribution from the loss of a hydrogen bond. PMID- 2204109 TI - Regulation of an enzyme by phosphorylation at the active site. AB - The isocitrate dehydrogenase of Escherichia coli is an example of a ubiquitous class of enzymes that are regulated by covalent modification. In the three dimensional structure of the enzyme-substrate complex, isocitrate forms a hydrogen bond with Ser113, the site of regulatory phosphorylation. The structures of Asp113 and Glu113 mutants, which mimic the inactivation of the enzyme by phosphorylation, show minimal conformational changes from wild type, as in the phosphorylated enzyme. Calculations based on observed structures suggest that the change in electrostatic potential when a negative charge is introduced either by phosporylation or site-directed mutagenesis is sufficient to inactivate the enzyme. Thus, direct interaction at a ligand binding site is an alternative mechanism to induced conformational changes from an allosteric site in the regulation of protein activity by phosphorylation. PMID- 2204112 TI - NIH director: sixth time lucky? PMID- 2204111 TI - Is there an EMF-cancer connection? PMID- 2204113 TI - The other human genome. PMID- 2204114 TI - Replicative senescence: the human fibroblast comes of age. AB - Human diploid fibroblasts undergo replicative senescence predominantly because of arrest at the G1/S boundary of the cell cycle. Senescent arrest resembles a process of terminal differentiation that appears to involve repression of proliferation-promoting genes with reciprocal new expression of antiproliferative genes, although post-transcriptional factors may also be involved. Identification of participating genes and clarification of their mechanisms of action will help to elucidate the universal cellular decline of biological aging and an important obverse manifestation, the rare escape of cells from senescence leading to immortalization and oncogenesis. PMID- 2204115 TI - Enzymatic coupling of cholesterol intermediates to a mating pheromone precursor and to the ras protein. AB - The post-translational processing of the yeast a-mating pheromone precursor, Ras proteins, nuclear lamins, and some subunits of trimeric G proteins requires a set of complex modifications at their carboxyl termini. This processing includes three steps: prenylation of a cysteine residue, proteolytic processing, and carboxymethylation. In the yeast Saccharomyces cerevisiae, the product of the DPR1-RAM1 gene participates in this type of processing. Through the use of an in vitro assay with peptide substrates modeled after a presumptive a-mating pheromone precursor, it was discovered that mutations in DPR1-RAM1 cause a defect in the prenylation reaction. It was further shown that DPR1-RAM1 encodes an essential and limiting component of a protein prenyltransferase. These studies also implied a fixed order of the three processing steps shared by prenylated proteins: prenylation, proteolysis, then carboxymethylation. Because the yeast protein prenyltransferase could also prenylate human H-ras p21 precursor, the human DPR1-RAM1 analogue may be a useful target for anticancer chemotherapy. PMID- 2204116 TI - [Prospects of the use of neoplasm antigens as markers of gynecologic diseases]. AB - CA-125 antigen was assayed in 108 patients with the most prevalent gynecologic diseases by enzyme immunoassay. Its blood levels were found to be under 35 U/ml in the patients with inflammatory diseases. In endometriosis and benign ovarian tumors CA-125 concentrations in the blood were elevated. Malignant tumors of the ovaries were detected in 80 percent of the examinees. CA-125 levels reduced after surgical treatment in 72 percent of patients. These data permit a conclusion that CA-125 diagnostic agent may be used to monitor the course of the postoperative period and assess the late results of treatment. PMID- 2204117 TI - [Changes in neural-mental function in epilepsy under the action of anticonvulsant therapy]. PMID- 2204118 TI - [Emergency diagnosis of DIC syndrome complicated by hemorrhage using an expert computer program]. PMID- 2204121 TI - Chloroquine-resistant Plasmodium falciparum malaria in the Kavango region of Namibia. AB - The sensitivity to chloroquine of Plasmodium falciparum from the Kavango region of Namibia was determined by a 24-hour test in vitro. Twenty-six isolates were successfully tested, of which 11 were resistant to a low degree, schizogony being inhibited at 8 pmol/well. The results of the Dill-Glazko test for the presence of 4-aminoquinolines in urine indicate that chloroquine is not widely used in the area. PMID- 2204120 TI - Acute rheumatic fever in adults. AB - Thirty-one adults with acute rheumatic fever were identified at Groote Schuur Hospital over a 10-year period. In keeping with other series, arthritis was the most common major criterion. However, unlike other series, cardiac involvement was a prominent feature. Two patients died and a further 4 required valve replacements as a result of the disease. This suggests that local factors are of importance in determining the morbidity of the disease and that physicians should consider acute rheumatic disease in adults who present with unexplained valvular disease or carditis. PMID- 2204122 TI - The role of R. B. Thomson and E. P. Stibbe--brief heralds of the science of anatomy in South Africa. Part I. R.B. Thomson. PMID- 2204123 TI - [Trophic effect of testosterone on erythropoiesis in the mouse]. AB - Some differences between erythropoietin biogenesis under the action of natural stimuli and that resulting from testosterone administration are commented. Evidences are presented suggesting that androgens, apart from amplifying erythropoietin production, might exert some action on the stroma as specific erythrocytic tissue. This action could be anabolic or trophic and not erythropoietin dependent, at least to some extent, its effect being applied on the quantitative erythropoietic homeostasis. PMID- 2204124 TI - [Interferon and chronic myeloid leukemia]. PMID- 2204125 TI - [Evaluation of a method for the determination of serum ferritin by chemiluminescence]. AB - The aim of this study was to assess a technique for serum ferritin determination by means of chemoluminiscence (Magic Lite, Ciba Corning) in a series of unselected patients. A group of 100 healthy blood donors (50 men and 50 women), in whom iron deficiency had been previously excluded, was used as control. The results were validate according to the Societe Francaise de Biologie Clinique guidances. The characteristics of the method and its comparison with IRMA and ELISA techniques are described here. Its major advantages are related with simplicity and sensitivity; the main disadvantage is the necessity to repeat every step in samples with ferritin levels over 1,500 ng/dl. PMID- 2204126 TI - [Pica and gastric bezoar]. PMID- 2204127 TI - Tumors metastatic to the orbit: a changing picture. AB - Clinical characteristics of tumors metastatic to the orbit are related to primary tumor biology, and vary substantially among the various primary types. Common known primary sites include breast, lung, prostate, and melanoma. Tumor presentations can be classified into four generalized syndromes of mass, infiltrative, inflammatory, and functional effects. We found the infiltrative syndrome of presentation to be more common than for other types of orbital neoplasm. Accurate diagnosis often depends on recognition of the types of clinical syndromes and on the use of diagnostic modalities such as computed tomography, magnetic resonance imaging, fine needle aspiration biopsy, and open biopsy. Special histologic techniques are often useful in determining the origin of these often poorly differentiated tumors, and can provide a basis for specific hormonal therapy. Ophthalmologists play a vital role in the diagnosis of metastatic cancer; the orbital tumor was the presenting sign of systemic cancer in 42% of the cases reviewed. Although the overall prognosis for patients with metastatic cancer is quite poor, specific therapy is available for a growing number of cancers. Timely intervention based on accurate diagnosis can dramatically improve the duration and quality of life with selected tumors. PMID- 2204128 TI - Corneal pathophysiology with contact lens wear. AB - Contact lens wear induces a wide spectrum of changes in the appearance and function of the cornea. The most salient effect of lens wear is the hypoxically induced reduction in the rate of metabolic activity of the corneal epithelium and its sequellae. Other important alterations to corneal health associated with contact lens wear may be caused by antigenic and toxic stimuli, mechanical forces, osmotic effects and carbon dioxide retention. Perhaps the most important task facing the contact lens clinician is to distinguish between an acceptable state of physiological modification and an anomalous or pathological state of hypofunction. In this article, we review the assortment of corneal changes primarily on the basis of the causative agents and time scale with reference to the physical and chemical processes leading to the observed signs or symptoms. This procedure allows a strong foundation for understanding the etiology and management principles for the variety of effects that contact lenses may have on the cornea. PMID- 2204129 TI - Anterior chamber associated immune deviation: the privilege of immunity in the eye. AB - Immune privilege in the anterior chamber of the eye, no longer considered a laboratory curiosity, results from an active, if deviant, systemic immune response. The specific features of this response, termed Anterior Chamber Associated Immune Deviation (ACAID) include (a) suppressed delayed hypersensitivity, (b) preserved humoral immunity, and (c) primed cytotoxic T cell responses. Induction of ACAID by intraocular antigens depends upon unique characteristics of the anterior segment of the eye and of the spleen. Evidence from animal models is presented in support of the contention that ACAID is an evolutionary adaptation of the immune response designed to provide those types of immune protection for the eye that interfere with vision as little as possible. ACAID may also have been created for the purpose of avoiding harmful immune responses (autoimmune diseases) to unique molecules of the eye (such as retinal S antigen), which the immune system never learns to regard as "Self." Because of this adaptation, the eye and the host are vulnerable to those pathogens whose elimination is dependent upon delayed hypersensitivity, such as malignant tumors and herpes simplex virus-1. As we come to understand the cellular and molecular mechanisms responsible for ACAID, a new generation of therapeutic strategies may be envisioned for certain eye diseases which are now of enigmatic cause and submit poorly to conventional therapy. PMID- 2204130 TI - Research into the results of resection of hilar bile duct cancer. AB - We found mentions of 581 resections of hilar bile duct cancer in the literature to January 1989. Resection in 499 patients, reported or updated since 1980, resulted in an operative mortality of 12% and a 5-year survival rate of 13%. Resections confined to the hepatic duct confluence or extended to the quadrate lobe led to an 8% operative mortality and a 7% 5-year survival rate, although resections combined with major liver resection gave a 15% operative mortality and a 17% 5-year survival rate. Despite the best treatments available, present-day resection modalities are usually still not radical. Extension of resection in the retrohilar and hepatoduodenal direction might further improve the long-term surgical results. PMID- 2204131 TI - Primary hyperparathyroidism in a hypothyroid child. AB - Congenital hypothyroidism may result in severe mental retardation if this condition is not diagnosed in the neonatal period. Primary hyperparathyroidism in children is even more uncommon, and by 1977 had been reported in only 60 children under the age of 16 years. To our knowledge, we are reporting the first child with both congenital hypothyroidism and primary hyperparathyroidism. Because the normal anatomic relationship of the parathyroid glands to the thyroid gland was absent, preoperative localization studies were necessary. Ultrasonography, radionuclide scanning, and magnetic resonance imaging all indicated a right paratracheal mass in the region where the right lobe of the thyroid gland should be located. At operation, a single, enlarged parathyroid gland that measured 1.5 X 1.2 X 0.5 cm and weighed 500 mg was removed. The discharge serum calcium level was 9.3 mg/dl and has remained normal 2 years later. PMID- 2204132 TI - Esophageal lymphangioma: case report and review of the literature. AB - We report a 66-year-old patient with an esophageal lymphangioma. Five other cases have been reported previously. Clinical features, diagnosis, and therapy are discussed. PMID- 2204133 TI - [Dilated cardiomyopathy and Abramov-Fiedler myocarditis]. PMID- 2204135 TI - [The clinico-diagnostic aspects of rheumatism today]. PMID- 2204134 TI - [The clinical aspects of Lyme disease]. PMID- 2204136 TI - [New functions of antibodies]. PMID- 2204137 TI - [The biophysical chemistry of complement-fixing DNA-anti-DNA immune complexes]. PMID- 2204138 TI - [Soviet military medicine in World War II]. PMID- 2204139 TI - [The efficacy of immunomodulating therapy in rheumatoid arthritis]. PMID- 2204141 TI - [Modern therapeutic methods in Raynaud's syndrome]. PMID- 2204140 TI - [The evaluation of the therapeutic efficacy of auranofin in juvenile rheumatoid arthritis (the results of Soviet-American research)]. AB - The authors describe the results of prospective multicenter Soviet-American placebo-controlled 6-month investigations concerned with assessment of the therapeutic efficacy of auranofin in juvenile rheumatoid arthritis (JRA). 231 patients with JRA were placed under observation. Auranofin was found to be slightly superior to placebo. The drug was tolerated well. It is noted that in the treatment of JRA, of importance are long (6-month) courses of non-steroidal anti-inflammatory drugs. PMID- 2204142 TI - [Gastroenteropathies in patients with periodic disease and amyloidosis]. AB - The reported and the authors' data are provided on the pathogenesis, morphofunctional characteristics and clinical manifestations of acute and chronic gastroenteropathies in patients suffering from periodic disease with and without amyloidosis. Under discussion is the significance of changes in the gastrointestinal tract for the diagnosis of periodic disease, its association with other diseases and early recognition of amyloidosis. PMID- 2204143 TI - [New approaches to the basic therapy of rheumatoid arthritis]. PMID- 2204144 TI - Left ventricular thrombectomy in the early postinfarction period. AB - Emergency left ventricular thrombectomy was performed on four patients soon after infarction. In three patients surgery was carried out after embolisation had occurred and when a large, residual, protruding, mobile thrombus remained in the left ventricle. Surgery was performed in the fourth patient after a high risk thrombus was detected and initial attempts to lyse it had failed. All four patients had an uneventful recovery and were discharged within two weeks of surgery. These cases indicate that the therapeutic option of left ventricular thrombectomy is feasible for patients with acute infarcts and problematic left ventricular thrombi. PMID- 2204145 TI - Molecular biology and respiratory disease. 6. Modern molecular biology and respiratory bacterial infections: a revolution on the horizon. PMID- 2204146 TI - The fallacy of the lacune hypothesis. AB - We review the definition, pathogenesis, natural history, and prognosis and describe the first experimental model of lacunes. Defined pathologically or radiologically, lacunes are small cerebral infarcts which become cystic and are caused by occlusion of small arteries. The clinical definition of lacune is confused. The word "lacune" means a small stroke. While the immediate mortality rate from a small stroke is low, many patients are unable to return to work and the long-term prognosis is guarded. Photochemical damage to the carotid artery of rats produces microemboli to the brain, resulting in cavitary lesions resembling lacunes in humans. The "lacune hypothesis" is a fallacy because small cerebral infarcts are not caused solely by a combination of hypertension and small vessel disease, and the various "lacunar syndromes" are simply small strokes which should be investigated as such. PMID- 2204147 TI - A simple test to assess cerebrovascular reserve capacity using transcranial Doppler sonography and acetazolamide. AB - The goal of this study was the development of a simple bedside test to assess cerebrovascular reserve capacity using transcranial Doppler sonography. We studied 33 normal persons at rest and after stimulation of cerebral blood flow with 1 g acetazolamide. Their mean +/- SD increase in blood flow velocity in 54 middle cerebral arteries 10 minutes after stimulation was 24.4 +/- 9.2 cm/sec. We tried to validate the increase in blood flow velocity as cerebrovascular reserve capacity in 21 patients with obstructive carotid artery disease and symptoms of cerebral ischemia. The patients were studied using transcranial Doppler sonography and xenon-133 dynamic single-photon emission computed tomography after acetazolamide stimulation. Their increases in blood flow velocity (delta FV) and increases in cerebral blood flow (delta CBF) correlated significantly in both hemispheres (asymptomatic: Y = 0.32X + 10.65, r = 0.45, p = 0.04; symptomatic: Y = 0.36X + 2.28, r = 0.59, p = 0.004). There was no significant difference between the slopes of the regression lines. Blood flow velocity and cerebral blood flow at rest were not correlated. The increase in blood flow velocity after acetazolamide stimulation offers a simple and reliable method for assessing cerebrovascular reserve capacity. PMID- 2204148 TI - Nimodipine posttreatment does not increase blood flow in rats with focal cortical ischemia. AB - We used laser-Doppler flowmetry to study the effect of nimodipine administered after the onset of focal cortical ischemia on regional cerebral blood flow in 16 halothane-anesthetized, mechanically ventilated Wistar rats. We selected the Wistar rats strain since it would provide a wide range of ischemia severities to test the vascular response to nimodipine. Laser-Doppler probes continuously recorded regional cerebral blood flow at two or three sites over the parietal cortex (dura intact) while brain temperature was regulated at 37 degrees C. Occlusion of the right middle cerebral and common carotid arteries reduced cerebral blood flow to a mean of 38% (range 13-77%) of baseline. Thirty minutes later, either 2 micrograms/kg/min nimodipine (n = 8) or its vehicle, polyethylene glycol 400 (n = 8), was administered by a continuous intravenous infusion. Over 60 minutes of treatment, both the nimodipine-treated and vehicle-treated groups showed a trivial (3%) mean increase in cerebral blood flow. Nimodipine failed to augment cerebral blood flow regardless of whether the cortex was severely, moderately, or mildly ischemic. PMID- 2204149 TI - [The forensic medical diagnosis of death-cup poisonings]. AB - Comparative analysis and evaluation of all modern methods used for medicolegal diagnosis of poisoning with Amanita phalloides are presented. Imperfection of methods used for laboratory diagnosis of such poisonings requires extensive experimental control using the designed method of liquid chromatography for amanitine and phalloidine assay in the cadaveric organs and tissues. PMID- 2204150 TI - The future of neonatal therapeutic drug monitoring. AB - For many drugs, therapeutic drug monitoring (TDM) has become widely available and accepted as an important component of clinical decision-making in the intensive care nursery setting. This review analyzes the potential factors that can either expand or restrict neonatal TDM. A case is made for the development of pharmacokinetic services designed to meet the needs of sick neonates. These patients are well known for their extreme physiological instability, often resulting in drug concentrations obtained in non-steady-state conditions. Potential for toxic effects is also increased in this population. Appropriate collection and interpretation of measured concentrations is critical. The future of neonatal TDM is linked to that of TDM services in general. High cost, expensive technology, and ethical and political factors, however, set apart the population of very low birth weight infants from the universe of patients receiving TDM services. PMID- 2204151 TI - A simple and disposable visual measuring device to assay antiepileptic drugs from whole blood samples. AB - This study evaluated a new, simple, disposable visual measuring device (AccuLevel), which uses enzyme immunochromatography to indicate visually, without any instrument, the concentrations of three major antiepileptic drugs (AEDs) in small blood samples. Drug levels (30 values for diphenylhydantoin, 41 for phenobarbital, and 40 for carbamazepine) obtained by AccuLevel were compared with those obtained with the enzyme-multiplied immunoassay technique (EMIT). Results showed an excellent correlation between EMIT and AccuLevel data for the three major AEDs. The method appears to be particularly suitable in outpatients and in case of emergency. PMID- 2204152 TI - Comparison of human, bovine, and newborn calf serum in the preparation of external quality assurance samples for therapeutic drugs. AB - The accuracy and precision of drug measurements made by different analytical techniques of a range of eight antiepileptic drugs, four tricyclic antidepressants, theophylline, and digoxin in three different matrices, human, bovine, and newborn calf serum, were compared using data reported to the Heathcontrol External Quality Assurance Scheme over 18 months. Neither of the animal serum samples was universally satisfactory compared with human serum. The newborn calf serum sample produced results that were closer to the spiked drug concentrations than those in bovine serum for most of the analytes covered by the survey. Both animal samples were unsuitable for digoxin, for which the use of scarce human material is recommended. PMID- 2204153 TI - Why are proteins O-glycosylated? AB - The O-linked oligosaccharides of glycoproteins are usually clustered within heavily glycosylated regions of the peptide chain. Steric interactions between carbohydrate and peptide within these clusters induce the peptide core to adopt a stiff and extended conformation and this conformational effect appears to represent a major function of O-glycosylation. PMID- 2204154 TI - The role of amylin in the insulin resistance of non-insulin-dependent diabetes mellitus. AB - Decreased responsiveness of glucose metabolism to insulin in skeletal muscle and the liver (insulin resistance or insensitivity) is characteristic of many conditions, including non-insulin-dependent (type II) diabetes mellitus. Most current work in this area centres on the hypothesis that the primary defect is an impairment of insulin binding and/or transduction of the insulin signal in affected tissues. However, studies imply that defects in the post-insulin receptor signaling pathways are of primary importance in the causation of insulin resistance. Amylin, a novel pancreatic hormone, secreted along with insulin from the pancreatic beta-cells, can modulate insulin effects, to produce insulin resistance in skeletal muscle and liver. PMID- 2204155 TI - Unraveling the complexities of transcription by RNA polymerase III. AB - The biosynthesis of proteins and nucleic acids in eukaryotes requires the participation of numerous small RNAs, many of which are products of RNA polymerase III transcription. How cells are able to coordinate the synthesis of these RNAs during growth and replication has been the subject of recent exciting and thought-provoking studies. We review the progress in this area, and focus upon shared properties between transcription systems having different functions. PMID- 2204156 TI - Peptide sequences that target cytosolic proteins for lysosomal proteolysis. AB - Lysosomes take up and degrade intracellular proteins in cultured cells in response to serum deprivation, and in tissues of organisms in response to starvation. One mechanism by which proteins enter lysosomes for subsequent degradation requires that substrate proteins contain peptide sequences biochemically related to Lys-Phe-Glu-Arg-Gln (KFERQ). PMID- 2204157 TI - Beta-galactoside transport in E. coli: a functional dissection of lac permease. AB - The polytopic membrane protein lac permease harnesses energy from the electrochemical H+ gradient to transport beta-galactosidases against a concentration gradient. Although high-resolution structural information is still lacking, the permease is thought to possess 12 membrane-spanning alpha-helical segments. Various experimental strategies, including site-directed mutagenesis, have been employed to probe the function of this membrane protein at the molecular level. PMID- 2204158 TI - Functional domains of assimilatory nitrate reductases and nitrite reductases. AB - Biochemical investigation of nitrate assimilation enzymes spans the past four decades. With the molecular cloning of genes for nitrate reductases and nitrite reductases, exciting new prospects are developing for the study of these enzymes. As large, complex enzymes with multiple redox centers, these two types of reductases should help us gain understanding of structural, functional and evolutionary relationships among the diverse group of multicenter redox enzymes. PMID- 2204159 TI - In the beginning is the end: regulation of poly(A) addition and removal during early development. AB - The addition of poly(A) tails to nearly all mRNAs within the nucleus was reviewed in the July issue of TIBS. Here we shift focus to the fate of poly(A) tails during early development. At specific times during oogenesis and embryogenesis, the poly(A) tails of certain maternal mRNAs are lengthened, while the tails of a number of other mRNAs are removed. The selective poly(A) addition reactions are regulated by a short, U-rich sequence in the 3' untranslated region, while the removal of poly(A) from specific mRNAs is a 'default state', requiring no specific sequence. These regulated changes in poly(A) length are likely to play a major role in translational regulation in the egg and early embryo. PMID- 2204160 TI - The slow diffusion of the DNA paradigm into biology textbooks. AB - The science textbook is a complex product of social, commercial and intellectual forces rather than a simple collection of scientific facts. It can serve as a valuable tool in tracking the assimilation of scientific change, providing insight into scientific revolutions. PMID- 2204162 TI - Prenatal diagnosis by ultrasound in pregnancies at risk for autosomal recessive polycystic kidney disease. AB - In 15 pregnancies at risk of the autosomal recessive type of polycystic kidney disease (ARPKD), there were six recurrences (40%), five of which were diagnosed prenatally between 17 and 26 weeks (mean, 22 weeks). In the remaining affected case, normal kidney size and echogenicity were still present at 30 weeks of gestation. Fetal kidney enlargement and increased echogenicity are the key ultrasonographic signs for the detection of ARPKD. Absent fetal bladder filling and oligohydramnios were only documented in two of the six affected pregnancies. The variability in onset, the intrafamilial variability and the limitations of excluding ARPKD by second trimester ultrasound have to be considered when counselling a couple at risk for this particular disorder. PMID- 2204161 TI - Morphological characterization of carotid artery stenoses by ultrasound duplex scanning. AB - Ulcerations and intraplaque hemorrhages are thought to play an important role in the development of neurological deficits in carotid artery stenoses. To assess the ability of duplex scanning to predict plaque morphology we compared different sonographic criteria (plaque border, plaque density, plaque structure) with the morphological findings in 169 consecutive carotid endarterectomies (144 cases with diameter reduction greater than 50%). Two percent of the sonograms were inadequate, and 20% showed poor image quality. Regular plaque borders revealed a smooth or at most minimally ulcerated surface in 92%. Grossly ulcerated stenoses, however, were only found in 27% of the irregular plaques. Moreover, the plaque border was nonvisible in 35% of all cases. Simple, fibro-atheromatous plaques were found to be echogenic in 72% and echolucency was present in 80% of the stenoses with relevant intraplaque hemorrhage. In conclusion, duplex scanning proved to be capable of detecting smooth, fibro-atheromatous stenoses with high accuracy. Ulcerations, however, cannot be predicted reliably, and intraplaque hemorrhage cannot be differentiated from atheromatous debris. PMID- 2204163 TI - Clinical performance of a cone/annular array ultrasound breast scanner. AB - Ultrasound is a useful adjunctive imaging modality to x-ray mammography for the detection and management of breast disease. A high resolution (0.3 mm at -6 dB) transducer consisting of co-axially aligned cone and annular array transducers has been incorporated into a prototype breast imaging system. The prototype scanner had an operating frequency of 4 MHz and scanning was performed in the prone position. We hypothesized that the increased resolution of this system would lead to improved detection of smaller, nonpalpable lesions and would thus contribute to the early detection of breast cancer. Results of a four year clinical study of the prototype involving 1743 patients are reported. The overall true positive (TP) fraction for the detection of malignancy was 52.5% compared with 86.6% for x-ray mammography. Improved performance of ultrasound approaching that of mammography is demonstrated for the youngest age group (less than 34 years) and for women whose breasts are predominantly dysplastic. However, the detection of nonpalpable tumours is disappointing with a TP fraction of only 22%. Causes for the failure of the prototype breast scanner to detect early breast lesions are presented and general conclusions on the use of large aperture transducers for automated breast imaging are discussed. PMID- 2204164 TI - A comparison of three different filters for speckle reduction of Doppler spectra. AB - This paper is concerned with speckle suppression in Discrete Fourier Transform based Doppler signals by means of digital image processing. The Doppler spectrum is treated as a greyscale image, and three different noise smoothing algorithms are applied to it. These are the Double Window Modified Trimmed Mean filter, which is nonlinear, and Lee's and the directional filter, which are adaptive in the sense that the smoothing performed by them at each point of the image is controlled by a local image measure. In order to evaluate the performance of the filters, they were applied to a variety of regular waveforms obtained from a physiological flow phantom. Ensemble averaging of a large number of unfiltered spectra was used as the "gold standard" in the evaluation, i.e., as the output of an ideal filter which reveals the exact nature of the underlying Doppler spectrum after speckle has been eliminated. Comparison of the "gold standard" with the ensemble averaged filtered data allowed the noise reduction, bias and distortion of the maximum frequency envelope introduced by filtering to be examined. Overall, the best performance was offered by the directional filter whose action was controlled by the combination of the local edge content and the slope of the least-squares-fit line passing through the data points along each particular direction. PMID- 2204166 TI - Source of Doppler shift in blood flow. PMID- 2204165 TI - Ultrasound attenuation coefficient in the fetal liver as a function of gestational age. AB - An apparent increase in the ultrasound attenuation coefficient per unit frequency, alpha f, of fetal liver as a function of gestational age has been observed. Measurements were made in utero with a 25 megasample/sec RF digitizer and a real time ultrasound system with a 5 MHz scan head. A precise measurement of alpha f was employed in which the intercept was tied to 0 at a frequency of 0. In 178 examinations of normal pregnancies, the linear regression of the alpha f increased 26% between 26 and 40 weeks gestation. This statistically significant increase (p less than 0.0001) is consistent with several observations, those of Parker et al. of increased attenuation in liver when glycogen is added, the increasing glycogen storage in the liver before birth, and our own pre- and postnatal measurements reported elsewhere. A noninvasive assay for glycogen content would have important applications in medicine and biomedical science. However, an increase in measurement accuracy and precise correlation with glycogen content will be required to make meaningful predictions in individual cases, as opposed to the present statistical trends. PMID- 2204167 TI - [The diagnosis and treatment of arterial hypertension in patients on hemodialysis treatment and after a kidney allograft]. AB - Analysis of examination and treatment of 104 patients who were periodically exposed to hemodialysis and 60 persons who sustained the allotransplantation of a cadaveric kidney enabled the authors to reveal the incidence of arterial hypertension before and after the transplantation. Pronounced arterial hypertension (AH) was documented in patients who were treated with hemodialysis sessions for the proper renal diseases developed in angionephrosclerosis (chronic glomerulo- and pyelonephritis). In those who sustained the transplantation, AH was pronounced in case of acute of chronic rejection, transplanted artery stenosis of renal renin hyperproduction. Higher incidence of AH (2.3-fold higher) was observed in posttransplantation patients with the native kidney left. It correlated with higher peripheral plasma renin activity (RRA). The authors suggested that the scheme should be used for the diagnosis of AH manifestation both before and after the transplantation which included the account for the cause of the disease terminal stage, the character of the AH variance in hemodialysis captopril testing, radiocardiographic examination, indirect renal angiography (99-Tc pertechnetate) or selective blood testing for RPA in case bilateral nephrectomy should be made in two stages. For the patients who had sustained the transplantation of the kidney, the diagnostic scheme should include a double pulse Doppler sonography, arteriographic investigation of the transplant and pharmacorenography with a captopril load test. Advisability of captopril stimulation of renin secretion during the selective sampling of the blood was demonstrated. The authors verified the time-course of renin activity, the concentration of aldosterone, cortisol and adrenocorticotrophic hormone in patients with a history of bilateral nephrectomy, defined the indications for bilateral nephrectomy associated with AH and discussed its possible outcomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2204169 TI - [The pathogenesis and results of the surgical treatment of stress urinary incontinence in women]. AB - The paper presents the incidence rate (3-19.6%) of stress-induced enuresis (SIE) in females. The impact of birth injuries, obstetric instrumentation and heavy physical work resulting in the impairments of the sphincter-detrusor system of the bladder and the musculature of the pelvic bottom on the pathogenesis of SIE is indicated. As a result the bottom of the bladder, the posterior walls of the neck and urethra moved backward to form an obtuse angle with an anterior wall of the urethra that was roentgenologically evidenced as vesiculation. In this line the angle between the anterior and posterior walls of the urethra and neck became more obtuse with no contact upon contractility of their muscles which caused the stress-induced escape of urine. To eliminate vesiculation and enuresis, the authors used successfully the technique of urethral angulation by the duplication formed by the anterior vaginal wall over the cervix and urethra followed by their fixation to the posterior surface of the pubic area on one side and free skin graft on the other. Hebell-Schteckel's technique was a prototype for the method proposed. A total of 156 females with stages II and III SIE were successfully operated on. The results of 1-15 year follow-ups were good and satisfactory in 97 (89.9%) of 109 females. The relapses were more common in the females who had a repeated delivery or were engaged in heavy physical work as well as in two persons operated on in the menopause. PMID- 2204168 TI - [Ultrasonic study of the parathyroid glands in patients with coralliform nephrolithiasis]. AB - Functional activity of the parathyroid glands (PTG) is important for the choice of proper therapeutic policy in patients with dendritic nephrolithiasis. The location of the hyperfunctioning gland (usually adenomatously or hyperplastically changed) is a complicated problem as the dimensions of the gland are extremely small. Ultrasonic investigation of the parathyroid gland area for detection of the enlarged gland is used at the Research Institute of Urology, the RSFSR Ministry of Health. Linear (7.5 mHz) and sector (5 mHz) transducers have been used through the water medium and by the immediate contact with the surface of the patient's neck. A total of 24 subjects were enrolled in the study (13 females and 11 males aged 23-64 years). Enlarged parathyroid glands situated in the lower thyroid lobe (low parathyroid glands) or in the upper medial third of the thyroid lobe (upper parathyroid glands) were recorded in 9 patients and confirmed in the course of surgeries. In one case, the enlarged parathyroid gland was found in the thyroid tissue. Its length varied from 0.6 to 1.5 cm and its thickness, from 0.4 to 0.9 cm. All the glands were echographically evidenced as oval formations with a low-rate echogeneity and clear-cut smooth contours. In 3 cases the site of the gland was confirmed by a selective testing of the neck venous blood for parathyroid hormone. Histological examination of the removed glands revealed that hyperplastic changes were more common than the adenomatous ones. PMID- 2204170 TI - Chronic periaortitis--a new interpretation of Ormond's disease. PMID- 2204171 TI - Enolase isozymes in seminoma. AB - We determined concentrations of alpha and gamma-enolases in normal testis and in seminoma tissues by enzyme immunoassay. Concentrations of alpha-enolase were 4,170 +/- 2,040 ng/mg protein in normal testis (n = 8) and 8,140 +/- 4,480 ng/mg protein in seminoma (n = 8). Concentrations of gamma-enolase in seminoma (460 +/- 571 ng/mg protein) were significantly higher than those of normal testis (59 +/- 15 ng/mg protein). Immunohistochemistry showed positive tumor cells for gamma enolase in 6 of 8 seminoma cases (75%). Serum gamma-enolase levels were elevated (greater than 6.0 ng/ml) in 9 of 12 patients (75%) with seminoma: 60% of stage I, and 100% of stages II and III. In 10 patients treated by surgical excision and chemotherapy, serum gamma-enolase was significantly reduced after the treatment. These findings indicate that elevated serum gamma-enolase is derived from enhanced gamma-enolase in seminoma tissues, and that serum gamma-enolase could be a useful biomarker for staging and monitoring clinical course in patients with seminoma. PMID- 2204172 TI - Experimental studies of chemosensitivity testing of urothelial cancer grown in nude mice. AB - The present study provides information relevant to a number of variables which may influence response to treatment of nude mouse-grown human urothelial cancer. A number of xenotransplanted tumors were exposed to selected treatments at different transplant generations, and at various dose levels and treatment schedules. It was observed that nude mouse-grown tumors were characterized by consistency, reproducibility and biological stability not affected by the transplant generation at which they were examined. Treatment related dose response curves were steep, the sharpness of the curves depending on the degree of tumor sensitivity. Best therapeutic results were obtained at the maximum tolerated dose of cytotoxic agents under study and of importance, a 20% to 40% dose reduction with the same treatment schedule resulted in little or no activity. In addition, treatment schedule, timing and sequence of treatments and to a certain degree, tumor grade were important variables which could influence tumor response. The nude mouse-human tumor system provides important preclinical guidelines on dose, schedule, sequence and timing of treatments and can assist in designing more efficient clinical trials. PMID- 2204173 TI - Acute and chronic bacterial prostatitis due to E. coli. Description of an animal model. AB - Inoculation of Escherichia coli (serotype O:6) into the bladder of male and female Mastomys (Praomys) natalensis produced severe prostatitis. In this rodent both male and female animals possess a well developed prostatic gland. The histologic and microbiologic course of the prostatic infection resembled strongly the human disease. Acute bacterial prostatitis was followed by the development of chronic bacterial or nonbacterial prostatitis. The infection persisted in some animals for up to six months. Prostatitis was observed histologically in all animals sacrificed six months postinfection. Animals responded to the infection with a rise of anti-lipopolysaccharide antibodies. No major morphologic differences were detected in the histologic pattern of the inflammatory process between animals with positive and negative bacterial cultures and between male and female animals. PMID- 2204175 TI - Veterinary Immunology and Immunopathology. Volumes 1-25, November 1979-August 1990. Cumulative indexes. PMID- 2204174 TI - Increased risk of urinary tract infection associated with the use of calcium supplements. AB - Since ions are known to influence the interaction between cells, we undertook an examination of the effect of various ions on bacterial adherence to uroepithelial cells. While most of the ions examined had no effect or decreased bacterial adherence, calcium ions significantly increased bacterial adherence. It was demonstrated, in vitro that as the concentration of calcium was increased to levels higher than normally found in the urine, there was a significant increase in bacterial adherence. It was also found that if the diet was supplemented with calcium there was an increase in the excretion of calcium in the urine and a corresponding increase in bacterial adherence when bacteria and uroepithelial cells were incubated in this urine. It is suggested that an excretion of excess calcium in the urine may lead to an increased bacterial adherence in vivo and an increased potential for urinary tract infections. PMID- 2204176 TI - [Party political work in medical institutions]. PMID- 2204177 TI - [Soldiers of mercy. Interview by P. A. Pal'chikov]. PMID- 2204178 TI - [The main results and lessons of medical support for the Soviet Army in World War II]. PMID- 2204179 TI - [S. S. Iudin and military field surgery]. PMID- 2204180 TI - [The formation and development of the organization of therapeutic care for the sick and wounded in the war years]. PMID- 2204181 TI - [In the people's memory]. PMID- 2204182 TI - [In the battles for the Dnieper (from the memoirs of a military physician)]. PMID- 2204183 TI - [The graduates of 1940]. PMID- 2204184 TI - [Medical support for the Soviet troops in the East Prussia Operation]. PMID- 2204185 TI - [Medical supplies for the troops during the Berlin Operation]. PMID- 2204186 TI - [The organization of the evacuation of the wounded and sick from the army in the field to the rear in the USSR]. PMID- 2204187 TI - [The evacuation of the wounded and sick by sea lines of communication]. PMID- 2204188 TI - [The organization of the treatment of military personnel with minor wounds in the Navy]. PMID- 2204189 TI - [The lessons of military medical expertise in the war years]. PMID- 2204190 TI - [The experience of World War II and the organization of epidemic control protection for a restricted contingent of Soviet troops in the Republic of Afghanistan]. PMID- 2204191 TI - [Voenno-meditsinskii zhurnal during the years at the front]. PMID- 2204192 TI - Prophylactic intravenous immunoglobulin in pre-term infants: a controlled trial. AB - Sixty-six pre-term infants of less than 30 weeks gestation consecutively admitted to either of two neonatal intensive care units were randomized to receive routine intensive care only or prophylactic intravenous immunoglobulin, 200 mg/kg body weight at 3-weekly intervals in addition to routine intensive care. Eleven babies, 6 in the control group and 5 in the treatment group, were withdrawn from the trial due to early death from extreme prematurity (7 babies), early return to the referring hospital (3 babies), and elective treatment with intravenous immunoglobulin for severe congenital septicaemia (1 baby). Of the 55 who remained in the trial, significantly fewer babies in the treatment group had infection, 8 compared to 17 (p = 0.01). This difference was not significant when blood-culture proven septicaemia only was considered, 8 compared to 14 (p = 0.09). Twenty-seven (84%) of 32 blood-culture-positive episodes of infection were caused by coagulase negative staphylococci. Serum IgG was significantly higher with treatment and achieved levels comparable to those of normal full-term babies at the same post natal age. PMID- 2204193 TI - [Current trends in the pharmacotherapy of peptic ulcer (a review of the problem)]. PMID- 2204194 TI - [The medical activities of A. P. Chekhov in the Ukraine]. PMID- 2204195 TI - [Marat--physician, scientist, revolutionary]. PMID- 2204196 TI - [The contribution of Prof. P. V. Biriukovich to the development of psychiatry in the Ukraine (on the 80th anniversary of his birth)]. PMID- 2204197 TI - [Fenigidin in the treatment of patients with chronic cholecystitis in combination with chronic ischemic heart disease]. AB - A study is presented of 58 patients with chronic cholecystitis associated with chronic ischemic heart disease. Single sublingual use of phenigidin was followed by ultrasonic examination and revealed elimination of signs of spasm of the sphincter apparatus of the biliary tract and improvement of evacuation of bile from the gallbladder. Peroral use of phenigidin (10-20 mg three times daily before meals for 2-3 weeks) was accompanied by a positive dynamics of clinical manifestations of chronic cholecystitis and chronic ischemic heart disease. Average indices of tolerance to physical loads (bicycle ergometric [correction of veloergometric] data) did not change essentially as a result of treatment. PMID- 2204198 TI - [Calcium antagonists in cardiologic practice (a review of the literature)]. PMID- 2204199 TI - [The role of humoral antibodies in the rejection of a kidney allograft (a review of the literature)]. PMID- 2204200 TI - [Patterns in the development of polyneuropathies in diabetics (a review of the literature)]. PMID- 2204202 TI - [Anaerobic bacterial infections of the lungs]. PMID- 2204201 TI - [Fibrin/fibrinogen degradation products in diseases of the respiratory organs (a review of the literature)]. PMID- 2204204 TI - [Amiodarone and the liver]. PMID- 2204203 TI - [Academician V. Kh. Vasilenko--eminent Soviet scientist and therapist, a great friend of Bulgaria]. PMID- 2204205 TI - [Headache]. PMID- 2204206 TI - [Management of patients with unstable angina pectoris]. PMID- 2204207 TI - [Insulin needs of insulin-dependent diabetics during biostator control and subcutaneous use of insulin]. AB - 20 insulin-dependent diabetics, aged 17 to 52 years, duration of the diabetes from 1 to 22 years and mean value of the glycated hemoglobin 13.5 +/- 3.6% were studied. The 24 h insulin needs were determined with the help of an artificial pancreas (Biostator) at the following constants of the algorhithm: KR = 70, KF = 67, BI = 80, RI = 12, QI = 40, FI = 400, BD = 55, RD = 25, QD = 20, FD = 200 The insulin needs determined by the biostator were compared with those given subcutaneously which had, led to compensation of the diabetes before discharge of the patients. The mean insulin dose by the biostator was 1.0% U/kg and that of the subcutaneous insulin treatment was 0.86 U kg the difference is statistically insignificant). The above mentioned constants are recommended as being more physiological for the determination of 24-h insulin needs for a subcutaneous insulin treatment of diabetes. PMID- 2204208 TI - [Treatment of obesity with a very low-energy dietetic regimen--the endocrine parallels]. AB - 25 patients with various degree of obesity treated with a very low-caloric diet (Dresden diet) were followed up dynamically. By an average clinical stay of 22 days a satisfactory reduction of the body mass with mean 6.6 kg was achieved at mean reduction of the body mass index from 34 to 31. The blood sugar level, immunoreactive insulin in the course of the oral glucose tolerance test, the 24 h rhythm of the plasma cortisol and the aldosterone level at rest and in orthostatic position at the beginning and the end of the dietetic treatment were followed up. The results achieved are discussed in relation to the reduction of the body mass. PMID- 2204209 TI - [A case of xanthogranulomatous pyelonephritis]. AB - A case of a 38 years old man with xanthogranulomatous pyelonephritis is presented. The ultrasound examination of the abdomen found a tumorous formation above the left kidney. Arterial hypertension and changes in the lipid metabolism were found clinically. The i. v. urography revealed more characteristic changes. The diagnosis xanthogranulomatous pyelonephritis is based on the computed tomography findings and the clinico-laboratory examinations. PMID- 2204210 TI - [Nosologic concept and new developments in the etiopathogenesis of reactive arthritis]. AB - Reactive inflammatory arthritis is caused by extraarticular infection with different arthritogenic microorganisms. The causative bacteria can not be cultured from synovial specimens, but bacterial antigens have been demonstrated in cells of synovial fluid and synovial membrane, respectively. Thus, latent intraarticular infection may be the cause of reactive arthritis. A model of the etiopathogenesis of reactive arthritis is described on the basis of recent immunological and microbiological findings. PMID- 2204211 TI - [Chlamydia-induced arthritis: diagnosis--follow-up--therapy]. AB - Chlamydia-induced arthritis (CIA) is an inflammatory reactive arthritis caused by extraarticular infection with Chlamydia trachomatis. CIA presents as peripheral arthritis or spondylarthropathy. Extraarticular manifestations are present in most but not all cases, Reiter's syndrome occurs only in a minority of patients. Detection of Chlamydia trachomatis in genitourinary smears and demonstration of serum-antibodies against chlamydial antigens lead to diagnosis. Analysis of synovial fluid reveals nonpurulent inflammatory synovitis and, in some cases, chlamydial antigen has been demonstrated in synovial specimens. The therapy of CIA combines physical medicine, NSAID and shortterm antibiotic treatment of the genitourinary infection. Whether longterm antibiotic therapy or-in chronic cases- DMARDs are successful, needs further investigation. PMID- 2204212 TI - [Yersinia-induced arthritis: new knowledge of pathogenesis, diagnosis and therapy]. AB - Yersinia infections have been identified in rising incidence as the cause of acute or subacute intestinal or extraintestinal diseases in the past two decades. Immunopathological manifestations of Yersinia infections, e.g. Yersinia-induced arthritis, have evoked special interest among clinicians and microbiologists. Beneath epidemiological and clinical characteristics this review focuses on recent progress in pathogenesis and serological and immunohistological diagnosis of Yersiniosis. Possible consequences for newly therapeutical approaches in chronic Yersinia-induced arthritis and spondarthritis were discussed. PMID- 2204214 TI - [Viruses and arthritis]. AB - A number of virus infections can induce acute, non-erosive arthritis. A thorough exploration of the patient's history and serological testing for viral infections are crucial to the diagnosis of virus-induced arthritis. Musculoskeletal involvement in infection with the HIV-virus is not a rare feature and will have to be considered more often in cases of acute arthritis, as the prevalence of HIV infection is increasing. Whether chronic arthritis, like rheumatoid arthritis, is induced by viral infection, is still a subject of intensive research efforts. PMID- 2204213 TI - [Mycoplasmas and arthritis]. AB - Since 1898 Mycoplasmas are known triggers of different diseases in various animal species. In man they can cause among others non-gonococcal urethritis. In addition they are discussed as triggering agents of arthritis. Besides septic arthritides in immunocompromised patients with hypogammaglobulinemia, they might be causative agents in sexually acquired reactive arthritis, as in Reiter's syndrome. Various diagnostic tests are available. Antibiotic therapy is derived from experience with urogenital infections, proved investigations are pending. PMID- 2204215 TI - [Practical differential diagnosis in acute arthritis]. AB - The most common cause for acute arthritis are crystal arthropathies, sero negative spondarthritides and reactive inflammatory arthritis. In any case, the possibility of a purulent-septic arthritis must be excluded because of the prognostic consequences. Precise rheumatological case history and careful examination are relevant tools in providing a differential diagnosis; laboratory findings may be of great help as well. A flow-chart is suggested for rational diagnosis. PMID- 2204216 TI - [New classification criteria of chronic polyarthritis]. AB - The criteria for the classification of the rheumatoid arthritis were defined more precisely, reduced and simplified in 1987 by the American Rheumatism Association. The more detailed specification was achieved at the cost of sensitivity. We find the revision positive as the classification criteria are supposed to mainly serve the purpose of systematic organisation and as a base for multicentered studies. Only then they can give a little help in diagnostic orientation. Never the criteria can take the place of the individual differential diagnosis and the observation of the development of the disease. PMID- 2204218 TI - [Concept and criteria of spondylarthritis]. AB - Since several rheumatic disease share common features, they led to the concept of the spondarthritides: ankylosing spondylitis, psoriatic arthritis, reactive arthritis, enteropathic arthritides, juvenile oligoarthritis (type II), and questionable pustolotic arthro-osteitis and Behcet's disease. Furthermore undifferentiated spondarthritides have to be considered. They occur more frequently than ankylosing spondylitis. Definite ankylosing spondylitis is classified according to the New York-criteria, which, however, do not identify the early stage of the disease. In these cases early diagnostic criteria proved to be useful. In a multicenter study the so-called ESSG-criteria were recently introduced for the classification of the whole group of spondarthritides. They are also helpful for the nosological classification of undifferentiated spondarthritides. PMID- 2204217 TI - [Long-term drug treatment of chronic polyarthritis: current status and perspectives]. AB - The therapeutic repertoire for the treatment of rheumatoid arthritis has been expanded to new disease-modifying antirheumatic drugs (DMARDs), like Auranofine, Sulfasalazine, and Methotrexate. Rheumatoid arthritis is not only a highly disabling disease but is now recognized to be related with increased mortality. Therefore, the aim of therapeutic strategies is the early induction of remission. The strategy for treatment of rheumatoid arthritis should be based on an analysis of the individual risk of a patient to develop severe illness. A concept of "risk oriented DMARD-therapy" of rheumatoid arthritis is proposed. PMID- 2204219 TI - [Progress in therapy of spondylarthritis]. AB - An update of the wide spectrum of therapeutic measures in the spondarthritides is presented with the example of ankylosing spondylitis. Most important is a life style adjusted to the disease with daily exercises and complementary physiotherapy. The most significant measures of physiotherapy, drug treatment, operation, and radiotherapy are discussed. Preliminary results indicate a long term effect of sulfasalazine in ankylosing spondylitis. Peculiarities in the treatment of psoriatic arthritis and of entheropathic arthritides are pointed out. PMID- 2204220 TI - [Fibromyalgia syndrome. Current contributions to the etiology, diagnosis and therapy of so-called "soft tissue rheumatism"]. AB - The fibromyalgia syndrome (FMS) is an extraarticular rheumatic disease. Typical features are the chronic, polytopic pain in the musculoskeletal system and the provocation of pain by pressure on defined tender points. Mainly medium age women are affected by the disease. In histomorphological studies of muscle tissue non specific changes were demonstrated, which were thought to be due to ischemia. Furthermore, sleep disturbance and a reduced pain threshold, which may be related to psychological factors, are discussed in the etiology. In FMS a primary and a secondary form related to other diseases can be differentiated. The treatment consists mainly of behaviour therapy and physiotherapy. PMID- 2204221 TI - [Patient education in rheumatology]. AB - Most of the patients with rheumatic diseases do not know enough about their disease and its treatment. This may influence patient's satisfaction and compliance. Patient education is a useful approach to reduce the negative consequences of the lack of knowledge and non-compliance. Rheumatologists have recognized patient education as an important part of the long-term management of rheumatic diseases. PMID- 2204222 TI - [Rheumatologic emergencies]. AB - Contrary to the widely assumed opinion there exist rheumatological emergency situations that affect patients hazardously. These cover complications of the antirheumatic therapy as well as complications of the disease itself. The paper gives an overview of rheumatological emergency situations and tries a systemic approach to a rheumatological emergency medicine. PMID- 2204223 TI - [Discussion forum medical ethics. B2. Physician's oath: still current? Critical observations on various professional ethical oath texts]. AB - Topicality, expressiveness and universal validity of current ethical vows in medicine are compared critically. Instead of outmoded formula Pellegrino's and Thomasma's suggestion for a new and mainly at patient autonomy-oriented vow is favored. PMID- 2204224 TI - [Discussion forum medical ethics. B7. Essence of the oath. Reflections on the substance of the oath]. AB - There can be no oath, which does not possess a very special quality of obligation. Inseparably from this, there must be a justification stage which includes transcendental references. PMID- 2204226 TI - [Compliance--a complex problem]. AB - During the past 15 years medical and psychological literature has increasingly focused on compliance or noncompliance as a relevant aspect of patient care. The following paper is an attempt at categorizing the large variety of factors with impact on compliance, aiming at a more differentiated view at this problem. The paper is complemented by a short questionnaire which should allow the therapist (physician/psychologist) to assess the compliance of his patients/clients. PMID- 2204227 TI - [Infective endocarditis--diagnostic and therapeutic management]. PMID- 2204225 TI - [Secretin versus cimetidine in the therapy of active bleeding from peptic gastroduodenal lesions. A prospective, randomized, double-blind, multicentric study]. AB - In a multicentric, prospective, double-blind, randomized trial 101 patients with active bleeding (Forrest, Type 1/b) from gastroduodenal ulcers or erosions were treated with secretin (n = 50, dose: 800 clinic units/24 hours) or cimetidine (n = 51, dose: 75 mg/hour). The bleeding and the effect of the therapy were endoscopically confirmed. The bleeding was stopped during 48 hours of treatment in 36 patients of the secretin treated group and in 25 of the cimetidine treated group (p less than 0.05). In 72 hours the control of bleeding was established in a total of 75 patients (41 secretin, 34 cimetidine; not significant). Surgery was necessary in 7 vs. 9 cases. The mortality was 1 vs. 4 cases. The mean transfusion requirements were 6.6 units in secretin- and 8.2 units in cimetidine treated group (p less than 0.01). There was no difference in rebleeding rate. The results show a trend in favour of secretin compared to cimetidine in the treatment of active bleeding from gastroduodenal ulcers or erosions. PMID- 2204228 TI - [Critical comments on evaluation and interpretation of statistical analyses]. PMID- 2204229 TI - [Ergometry as part of the medical examination for sports fitness]. PMID- 2204230 TI - [Sports medicine fitness evaluation for diving and rescue swimming]. PMID- 2204231 TI - [Sports medicine responsibilities in the boxing ring]. PMID- 2204232 TI - [Consultation by the Berlin surgeon Eduard Sonnenburg (1848-1915) on performing surgical therapy of appendicitis and perityphlitis]. PMID- 2204234 TI - [Video-screen work from an occupational medicine viewpoint]. AB - The problem of potential health implications in visual display units (VDUS) workers does not exist when the requested ergonomic equipment of the working place is realized. Repetitive gestures and compulsive attitudes must be avoided. A healthy or optimally corrected visual organ is a prerequisite, as well. According to the hitherto knowledge there is neither to observe a harm of the germ-cells with a raised risk of malformations and abortions due to the emission of electromagnetic waves of the VDUs nor health implication of the pregnant woman. The works doctor has to realize the medical care. PMID- 2204235 TI - [The history of the concept stress]. AB - The historical roots of the term are treated as well as the story of Selye's theory of biological stress as a nonspecific response of the body. In the discussion of preceding approaches to describe processes which today one would name stress, the importance of Francois Magendie and John Brown as precursors is accentuated. Additionally, neurophysiological and psychological aspects are discussed. PMID- 2204236 TI - [Walter Bradford Cannon (1871-1945). The professional activities of an outstanding physiologist]. AB - Cannon was an outstanding scientist (Research fields: digestion, circulation, sympathetic nervous system, endocrine secretions, emotions and behaviour, homeostasis, Cannon syndrome, wound shock) and also very engaged in international scientific cooperation. His work is shown on the base of some of his original articles, his autobiography and some essential secondary literature; the dates of his life are given at the end of the article. PMID- 2204237 TI - [The problem history of the toxin-antitoxin theory in medical microbiology]. AB - The paper presents the history of the toxin-antitoxin theory. It covers the working hypotheses of the pathological-anatomical and clinical research (Virchow and Oertel), the experimental evidence of the diphtheria toxin by Roux and Yersin, up to the discovery of the antitoxin effect by Behring. The differences between an experimental based theory and the speculative conceptions of that time are discussed. PMID- 2204233 TI - [Regulation of food intake]. AB - Regulation of food intake is commonly treated as a negative feedback-loop. Hunger and/or appetite lead man and animals to ingest food. The subsequent meal contingent activation of pre- and postabsorptive mechanisms then leads to satiety. The activation of oral and gastrointestinal chemo- and mechanoreceptors is important on the preabsorptive site. The gastrointestinal hormone cholecystokinin may also have a physiological satiety effect. Preabsorptive satiety mechanisms are influenced by the rate of gastrointestinal transit. The pancreatic hormone glucagon, which is released during meal taking, and various metabolites contribute to the postabsorptive regulation of food intake through activation of hepatic chemoreceptors, which are connected to the brain via predominantly vagal afferents. In addition, glucoreceptors in the brain, in particular in the nucleus of the solitary tract, contribute to food intake regulation by monitoring blood glucose concentration or, more specifically, glucose utilization. The nucleus of the solitary tract, which relays vagal afferents from gut and liver and also gustatory afferents, projects to the hypothalamus and to other forebrain structures. In this neural network the informations from the periphery are integrated by various neurotransmitters and neuropeptides, but the exact role of the substances involved is not fully understood yet. Body weight and, hence, body fat presumably affects feeding through modulation of a postabsorptive mechanism. PMID- 2204238 TI - [Serum enzymes in grade I hypertensive patients before and following a change in nutrition in relation to polyene acid and electrolyte content]. AB - In patients with mild hypertension the blood pressure reduction through n-3 fatty acids can be improved by an additional increase of the potassium intake. Metabolic processes can be followed up by determinating serum enzymes. By an additional daily intake of 200 g fish for 14 days the metabolism is hardly changed. The increased activity of the transaminases after diet is probably a consequence of the increased protein intake. PMID- 2204239 TI - [Liver diseases complicating pregnancy]. AB - Liver disease in pregnancy represents a broad spectrum of disorders. Most of the common forms of acute and chronic liver disease occur during pregnancy and often present special difficulties in diagnosis and management. In addition, there is a group of hepatic disorders unique to pregnancy, which also must be identified appropriately. Rapid institution of therapy is important in preventing the unfavorable perinatal outcome and maternal mortality. The changes in liver function related to gestation will be reviewed initially. The major forms of hepatic disease specifically associated to pregnancy will be then described and the obstetrical management as well as the therapeutic modalities proposed. PMID- 2204240 TI - [Fetal movement and acceleration behavior in unimpaired and impaired newborn infants]. AB - The following biophysical examination parameters were found by CTG-synchronous registration of fetal body and respiratory movements and compared in 7 fetuses impaired at birth (pHa less than 7.20, 1- and 5-minute Apgar scores less than or equal to 7 points) and 76 unimpaired born fetuses (pHa greater than or equal to 7.20, 1- and 5-minute Apgar scores greater than or equal to 8 points): number of fetal body movements per 10 minutes examination time; total and mean durations of these movements per 10 minutes; number of fetal respiratory movements per 10 minutes; number and total duration of fetal respiratory movement periods per 10 minutes; frequency of fetal respiratory movements; proportion of 10-minute periods with and without fetal body and/or respiratory movements and the amounts of the quotients from the amplitude of accelerations in fetal heart rate resulting from fetal body movements and the durations of these body movements. The mean interval between biophysical examination and childbirth was 11 days. Principally, the impaired born fetuses were less active in their movements than were unimpaired born fetuses. Apart from the frequency of fetal respiratory movements and the proportion of 10-minute periods without fetal body movements, the above mentioned parameters differ significantly with a probable error of alpha = 0.05. All biophysical parameters were registered on an uterus without labour and the cardiogram as well as the biophysical profile--with the exception of one fetus from the group of impaired borns--being unremarkable. The 10-minute periods without fetal body or respiratory movements were excluded from analysis. PMID- 2204241 TI - [Spontaneous regression of fetal megacystis in the 3d trimester]. AB - The sonographic diagnosis of a fetal megacystis in the first trimester is reported that later regressed spontaneously. Therefore, at first only follow-up examinations are indicated in case of early dilatation of the fetal bladder as the outcome may be normal. The case illustrates that great caution must be exercised in predicting an unfavorable outcome of fetuses with an early dilatation of the bladder. PMID- 2204242 TI - Inactivation of viral antigens for vaccine preparation with particular reference to the application of binary ethylenimine. AB - Viral antigens for human and veterinary vaccines are still inactivated with formaldehyde. This is not an ideal inactivant and the problems of formaldehyde inactivation of vaccines are discussed. Vaccines inactivated with aziridines are superior in safety and antigenicity. Aziridines inactivate viruses in a first order reaction and the inactivation rate and endpoint can be determined. The preparation and application of the aziridine compound binary ethylenimine (BEI) and the necessary conditions for and controls of the inactivation process are described and discussed. A computer program has been written for assistance in the use of BEI for controlled inactivation of viral antigens. PMID- 2204244 TI - New approach to develop a vaccine design against shigellosis. PMID- 2204243 TI - Studies in volunteers to evaluate candidate Shigella vaccines: further experience with a bivalent Salmonella typhi-Shigella sonnei vaccine and protection conferred by previous Shigella sonnei disease. AB - A bivalent vaccine consisting of Salmonella typhi strain Ty21a containing the 120 MDa plasmid of Shigella sonnei and expressing both S. typhi and S. sonnei lipopolysaccharides (LPS) on its surface was previously shown to protect significantly against S. sonnei disease in experimental challenge studies. However, protective efficacy could not be reconfirmed in volunteers with five subsequent lots of vaccine. One vaccine lot which resembled the initial protective lots of vaccine in biochemical and serological tests, and by electron microscopy, was administered to 16 volunteers who ingested three doses of 10(9) organisms each. Antibody secreting cells (ASC) specific for S. sonnei LPS were detected in the blood of 100% of vaccines, but no protection of these vaccines was demonstrated during a S. sonnei challenge study. To assess the ability of the volunteer model to detect infection-derived immunity, six volunteers who had had clinical shigellosis due to S. sonnei two months earlier were rechallenged with wild-type S. sonnei, together with 12 controls. Prior infection provided 100% protection against febrile illness (p = 0.05) and diarrhea (p = 0.04), thereby validating the volunteer model for assessing Shigella vaccines. PMID- 2204245 TI - Regulatory DNA-binding proteins in yeast: an overview. PMID- 2204246 TI - Purification of delta-aminolevulinate dehydratase from genetically engineered yeast. AB - Saccharomyces cerevisiae transformed with a multicopy plasmid carrying the yeast structural gene HEM2, which codes for delta-aminolevulinate dehydratase, was enriched 20-fold in the enzyme. Beginning with cell-free extracts of transformed cells, the dehydratase was purified 193-fold to near-homogeneity. This represents a 3900-fold purification relative to the enzyme activity in normal, untransformed yeast cells. The specific activity of the purified enzyme was 16.2 mumol h-1 per mg protein at pH 9.4 and 37.5 degrees C. In most respects the yeast enzyme resembles mammalian enzymes. It is a homo-octamer with an apparent Mr of 275,000, as determined by centrifugation in glycerol density gradients, and under denaturing conditions behaved as a single subunit of Mr congruent to 37,000. The enzyme requires reduced thiol compounds to maintain full activity, and maximum activity was obtained in the presence of 1.0 mM-Zn2+. It is sensitive to inhibition by the heavy metal ions Pb2+ and Cu2+. The enzyme exhibits Michaelis Menten kinetics and has an apparent Km of 0.359 mM. Like dehydratases from animal tissues, the yeast enzyme is rather thermostable. During the purification process an enhancement in total delta-aminolevulinate dehydratase activity suggested the possibility that removal of an inhibitor of the enzyme could be occurring. PMID- 2204247 TI - An essential gene in Saccharomyces cerevisiae shares an upstream regulatory element with PRP4. AB - ORF2 is an essential gene immediately upstream of PRP4 (formerly RNA4), a gene involved in nuclear mRNA processing in Saccharomyces cerevisiae. The two genes are arranged head-to-head. An 8 base-pair conserved sequence element is found upstream of both genes, as well as upstream of certain other genes that are known to be involved in pre-mRNA processing. Through deletion analysis we have found that both of the conserved sequence elements are important for transcription of both genes. We have cloned ORF2 and have isolated temperature-sensitive orf2 mutants. The phenotype of these mutants does not suggest a role for ORF2 in mRNA processing. The deduced amino acid sequence of ORF2 indicates significant similarity to DPR1, a gene encoding a protein that is involved in the carboxy terminal processing of G-protein. PMID- 2204249 TI - Dermatitis in broilers caused by Escherichia coli: isolation of Escherichia coli from field cases, reproduction of the disease with Escherichia coli O78:K80 and conclusions under consideration of predisposing factors. AB - A dermatitis in broiler chickens, especially on the caudal back, thighs and around the cloaca is observed more frequently in the last years. The skin is swollen at sites of inflammation and a fibrineous plaque extends between muscle and subcutis. No clinical signs are visible in the living flock but the disease causes economical losses because of degrading and rejection of carcasses. Studies of literature and own field observations suggest that Escherichia (E.) coli is involved in the development of the dermatitis. The following serotypes were isolated from field cases: O78:K80 (3X), O2:K56 (2X), O127:K63 (3X), O9:K57 (1X), O140 (2X); two isolates could not be identified. The reproduction of the dermatitis was successful by infection via feather follicles with E. coli O78:K80. The density of broilers kept on farms may contribute to the outbreak of dermatitis by violation of the skin followed by infection of the injuries. Massage of the infected sites by close contact of birds and insufficient hygiene may support the development of the disease. PMID- 2204248 TI - Analysis of the THR4 region on chromosome III of the yeast Saccharomyces cerevisiae. AB - The gene encoding threonine synthase (THR4) from the yeast Saccharomyces cerevisiae was cloned by complementation of a thr4 mutant. This gene was also found on a lambda clone (5239) consisting of a fragment of chromosome III inserted in the vector lambdaMG3. The THR4 gene encodes a protein of 514 amino acids (M.W. 58 kDa), which has extensive homologies with E. coli threonine synthase (thrC) and B subtilis threonine synthase. The 5' flanking region of the gene contains three regulatory sequences [TGACT(C)] for the general amino acid control (GCN). About 130 bp downstream of the THR4 gene another large open reading frame (563 amino acids) is found in the opposite orientation. This may imply that this open reading frame, called CTR86, shares a terminator region with THR4. The function of the protein encoded by CTR86 is not yet clear, but the fact that the upstream region contains a GCN4 responsive site suggests that the gene product may also be involved in amino acid biosynthesis. PMID- 2204250 TI - Evaluation of five different methods for routine diagnosis of rabies. AB - Brain tissue from 187 animals of different species was investigated by means of fluorescent antibody test, peroxidase anti-peroxidase technique, mouse inoculation test and cell culture technique for a diagnosis of rabies. With peroxidase anti-peroxidase technique the rabies specific reaction comprised inclusion bodies and a granular staining of the cytoplasm of affected cells. A specific positive reaction was found only in neurons, in which perikaryon as well as cell processes were affected. Fluorescent antibody test and peroxidase anti peroxidase technique detected 98% each, mouse inoculation test 95% and cell culture technique 81% of the rabies positive animals. In conclusion, peroxidase anti-peroxidase technique allows a highly reliable diagnosis of rabies when only formalin-fixed and paraffin-embedded material is available. Histopathological alterations comprising Negri bodies, inflammatory and degenerative lesions were encountered in 53% of the rabies positive brains. PMID- 2204251 TI - Clomiphene treatment for women with unexplained infertility: placebo-controlled study of hormonal responses and conception rates. AB - One hundred and eighteen patients with unexplained infertility were treated with clomiphene (Clomid, Merrell) in a randomized placebo-controlled cross-over study lasting up to 3 months with each preparation. Compared with placebo, clomiphene led overall to a 66% increase in mid-luteal serum progesterone levels (from mean 43 nmol/l to 71 nmol/l, p less than 0.001) and a 53% rise in the 3-month cumulative conception rate (from 14.6% to 22.33%, p less than 0.05). The greatest relative increase in conception rates with clomiphene was in women with infertility lasting more than 3 years (3-month rates from 2.9% to 14.4%, p less than 0.05). Differences in conception rates were not related to the rises in progesterone, and there was no carryover effect of clomiphene into the following placebo cycles in terms of progesterone levels or conceptions. The findings suggest that couples with unexplained infertility of less than 3 years duration are essentially normal, but with more than 3 years duration there is often a subtle disorder of ovulation that is corrected by clomiphene therapy. PMID- 2204252 TI - Increased maternal plasma concentration of endothelin-1 during labor pain or on delivery and the existence of a large amount of endothelin-1 in amniotic fluid. AB - The concentration of endothelin-1 (ET-1) in plasma and amniotic fluid from normal pregnant women was determined by a sensitive sandwich-enzyme immunoassay system, established recently. The plasma ET-1 level increased gradually during normal pregnancy as the pregnancy advanced, the levels (0.40 +/- 0.02 pmol/l, n = 45) being significantly (p less than 0.05) higher after 29 weeks of gestation than those (0.32 +/- 0.01 pmol/l, n = 30) before 28 weeks of gestation. The plasma ET 1 level during labor pain was significantly higher (0.59 +/- 0.06 pmol/l, n = 10) than that (0.40 +/- 0.02 pmol/l, n = 45) in the 3rd trimester of pregnancy without labor pain (p less than 0.02). Moreover, a high level of ET-1 (17.38 +/- 0.25 pmol/l, n = 18) was detected in amniotic fluid on term delivery. The ET-1 level in amniotic fluid was significantly higher than the levels in maternal and umbilical cord plasma (p less than 0.001 and p less than 0.001, respectively). After delivery the maternal ET-1 level decreased gradually and 2 day postpartum ET-1 levels reached the normal non-pregnant level. PMID- 2204253 TI - Insulinlike growth factor 1 regulates mRNA levels of osteonectin and pro-alpha 1(I)-collagen in clonal preosteoblastic calvarial cells. AB - A nontransformed rat clonal cell line (UMR-201) with phenotypic characteristics of osteoblastic precursor cells was found to respond to insulinlike growth factor 1 (IGF-1) by increased osteonectin and pro-alpha 1(I)-collagen mRNA expression. Cells were treated for 24 h with insulin, growth hormone, or IGF-1 to study the regulation of messenger RNA for osteonectin and pro-alpha 1(I)-collagen using Northern blot hybridization. UMR-201 cells possess specific high-affinity receptors for growth hormone, although there were no significant effects of growth hormone (10(-9)-10(-7) M) or insulin (10(-9)-10(-6) M) on mRNA species for osteonectin or pro-alpha 1(I)-collagen. However, IGF-1 increased both mRNA species from a concentration of 10(-9) M. The effect on osteonectin mRNA expression was likely due to increased transcription; when 5' flanking osteonectin (ON) genomic fragments were linked to the bacterial reporter gene chloramphenicol acetyltransferase (CAT) and introduced by transfection into UMR 201 cells, the transcriptional activity of the ON-CAT construct was increased 235 and 270% by 10(-8) and 10(-7) M IGF-1, respectively. In contrast, growth hormone did not change the transcriptional activity of the ON-CAT construct. In confirmation of other work, transforming growth factor beta (TGF-beta, 0.1-2.5 ng/ml) increased mRNA for osteonectin and pro-alpha 1(I)-collagen in a dose dependent manner. Transforming growth factor alpha (TGF-alpha) at 0.1-10 ng/ml had no consistent effects in repeated experiments on osteonectin and pro-alpha 1(I)-collagen mRNA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2204255 TI - Peritumoral brain edema. A keynote address. PMID- 2204254 TI - Impairment of macrophage colony-stimulating factor production and lack of resident bone marrow macrophages in the osteopetrotic op/op mouse. AB - Mouse calvaria-derived osteoblastlike cells have been shown to produce macrophage colony-stimulating factor (M-CSF). This factor may be involved in osteoclastogenesis and thus in bone resorption. In the present study we investigated whether the production of M-CSF was altered in the osteopetrotic mouse mutant strain op/op, characterized by a decrease in osteoclast number and an impairment of bone resorption. Whole calvariae and cells, as well as skin and lung fibroblasts, of the op/op mouse were found to produce no measurable M-CSF, in contrast to tissue and cells derived from normal littermates. M-CSF was identified by colony assay in semisolid media and by inhibition of the biologic activity with antiserum against M-CSF. Furthermore, the number of resident macrophages, identified by F4/80 antigen (F4/80 Ag) immunohistochemistry, was drastically decreased in bone and bone marrow of the op/op mouse, but in skin these cells were normal in number and morphology. These findings suggest that both M-CSF and resident macrophages play a role in the mechanism of bone resorption. The op/op mouse appears to be a valuable model to further investigate such a hypothesis. PMID- 2204257 TI - [Nutrition and food on youths' hikes in the first 3d of the 20th century]. AB - Based on original papers and diaries of the German scout movement (1900-1933), an extensive survey is given of the information available concerning the nutrition of children and youth in the scout movement and hiking groups. In contrast to the idea that strong sectarian influences affected their nutrition (vegetarianism etc.), the analyses and comparisons do not confirm this assumption. PMID- 2204256 TI - Ischemic cerebral edema. 5-Hydroxytryptamine receptors and the physical state of synaptosomal membranes. PMID- 2204258 TI - [Secular acceleration in psychological and somatic trends. A review]. AB - This is a review about the secular acceleration of psychic an somatic development over the last two decades. Based on empirical studies published in this field, the final tendency of this trend in growth and puberty, its continuance in sexual behaviour and mental capacity, as the possible consequences for personality development are discussed. The secular trend is interpreted as an effect of modification limited for genetic and ecological reasons. PMID- 2204259 TI - [Genetic aspects of the susceptibility for caries and marginal periodontitis]. AB - The main employment of stomatology with curative matters and material problems caused a neglect of genetic aspects in the aetiology of dental caries and marginal periodontitis. A critical review of literature is the base of proposals for consideration of genetic aspects in the fields of stomatologic epidemiology, dental health care programs and dental health care education. PMID- 2204260 TI - [Clinical utility of long-term administration of trapidil (MDR-1865) in the treatment of diabetic retinopathy]. AB - In order to investigate the usefulness of prolonged administration of trapidil in the treatment of diabetic retinopathy, a follow-up study was carried out after the end of a placebo-controlled, double-blind study of the drug in case of the trapidil-treated group who continued to be treated with 300 mg/day of trapidil (Rocornal) (TT group) and those of the placebo group who were not given any treatment after the end of the study (PP group). The TT group was significantly superior or tended to be superior to the PP group in improvement of hard exudates, retinal hemorrhages and soft exudates, and also in improvement of capillary microaneurysms on fluorescein fundus angiography. In the course of diabetic retinopathy by the global evaluation of findings in individual cases, the TT group was significantly superior or tended to be superior to the PP group. Photocoagulation was performed on 20 (28%) of 72 eyes of the PP group and 13 (19%) of 68 eyes of the TT group, with the mean interval to photocoagulation being 7.2 months for the PP group and 14.0 months for the TT group. There was a significant difference between the 2 groups in terms of the interval to photocoagulation. Randomized fundus photographic evaluation of the findings by the central evaluation committee showed that the TT group was significantly superior or tended to be superior in improving retinal hemorrhages, soft exudates and leakage of fluorescein dye, and was also significantly superior or tended to be superior in relation to the course of the retinopathy, which was consistent with the evaluation by the attending ophthalmologists.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2204261 TI - Rheumatoid arthritis: current concepts and management, Part 1. PMID- 2204262 TI - Human cardiac allograft rejection. Correlation of grading with expression of different monocyte/macrophage markers. AB - Endomyocardial biopsies from human cardiac allografts were investigated with the use of immunohistochemical methods. A correlation between the different degrees of rejection reaction and subtypes of monocyte/macrophage infiltrates was established. Early and mild rejection is characterized by recently immigrated monocytes/macrophages positive for the monoclonal antibody Ki-M1. In contrast, the cellular infiltrates in severe and resolving rejection show strong expression of antigens recognized by Ki-M6 and Ki-M8, indicating increased phagocytotic function of monocytes/macrophages. The immunohistochemical assessment of monocytes/macrophages can thus be used, in addition to conventional histology, in the diagnosis of cardiac allograft rejection. PMID- 2204263 TI - Rapid immunotyping of B-cell non-Hodgkin's lymphomas by flow cytometry. A comparison with the standard frozen-section method. AB - The authors compared immunotyping (IT) results obtained by both standard frozen section (FS) and flow cytometry (FC) methods on 218 biopsies suggestive of lymphoma to learn the advantages of each method. The independent interpretations of the FS and FC IT results were concordant in 93% (202 of 218) of cases. The 16 cases with discordance were reviewed and seven causes for discrepancy found: methodologic problems, focal lymphomatous involvement, more sensitive light chain detection by FC, inadequate sample for FC, interpretation error, sample mislabeling for FC, and unexplained. Eleven of the concordant B-cell non Hodgkin's lymphomas (NHLs) studied by FC did not have a kappa:lambda ratio of 3 or greater or 0.5 or less and were shown to express light chain restriction by a D-value of 15 or greater with the use of statistical analysis of the kappa and lambda histograms or by multiparameter analysis of large versus small cells. The authors found both methods to be effective for phenotyping lymphomas, however, each has distinct features, making them complementary in their applications. PMID- 2204264 TI - The periarteriolar lymphocyte sheath in immunodeficiency T- or B-lymphocyte area? AB - T- and B-lymphocyte populations in peripheral lymphoid tissues occur in distinct compartments (e.g., the periarteriolar lymphocyte sheath of the splenic white pulp is a T-cell area). The authors report on two patients with severe combined immunodeficiency (SCID) and one patient with immunodeficiency after anti-T-cell treatment for rejection of a heart transplant, in which the area surrounding the central arteriole in spleen white pulp was well-populated despite T-cell deficiency (documented by, for example, severe depletion of lymph node paracortex). Immunologic phenotyping showed the B-lymphoid lineage of lymphocytes at this location. The framework in the periarteriolar area consisted of follicular dendritic cells, which are typical framework components of B-cell areas. We conclude that assessment of only conventional histopathology of the spleen in these patients leads to erroneous conclusions about the type of immunodeficiency and that immunologic phenotyping is required to document the exact nature of the deficiency. PMID- 2204265 TI - A new slide latex agglutination test for the diagnosis of acute Candida vaginitis. AB - Two hundred two slide latex agglutination (SLA) tests were performed on 137 women attending a vaginitis clinic to evaluate the efficacy of this new test in diagnosing acute symptomatic Candida vaginitis. In 77 patients with acute Candida vaginitis, the SLA test revealed a positive reaction in 56 patients, reflecting a sensitivity of 72.7%, lower than that observed with the 10% potassium hydroxide microscopic examination (sensitivity 90%). False negative SLA reactions could not be accounted for by lower numbers of yeast cultured from the vagina or by the presence of nonalbicans strains of Candida. Following successful antimycotic therapy, the SLA test promptly became negative in all mycologically negative patients. Application of the SLA test in asymptomatic healthy control women revealed extremely few false positive reactions for Candida (5.6%). This easily performed and rapid slide latex agglutination test should provide a useful adjunct to the diagnosis of Candida vaginitis, but only for physicians who do not routinely perform microscopy on vaginal secretions. PMID- 2204266 TI - Clonal immunoglobulin gene rearrangement in nodular lymphoid hyperplasia of the gastrointestinal tract associated with common variable immunodeficiency. AB - The authors report a case of common variable immunodeficiency associated with nodular lymphoid hyperplasia of the gastrointestinal tract in which a clonal population of lymphoid cells was detected by immunophenotypic and genotypic studies on tissue obtained by colonoscopic biopsy. The patient has been followed up for more than 50 months without clinical, radiographic, or pathologic evidence of lymphoma. The significance of clonal rearrangement in the setting of immunodeficiency and the role of genotypic studies in defining lymphoid malignancy are discussed. PMID- 2204267 TI - Radiological cases of the month. Obstruction of the trigone of the bladder by balloon of Foley catheter. PMID- 2204268 TI - Update on the immunodeficiency diseases. AB - Newer understanding of the development of the immune system and novel methods to repair these defects promise cures for previously fatal diseases. The advances stem from the ability to define the developmental stages and describe the diseases at the gene level. Coordinate with this progress, recombinant DNA technology may soon permit the precise correction of the defect. For the moment, gene replacement is accomplished at the cellular level by bone marrow transplantation. Here too, rapid clinical advances now permit the use of nonsibling donors. The long-term results are equivalent to those obtained in the past when only HLA-matched siblings could donate. There is now a support group that is of inestimable value to the families of those who suffer from immunodeficiency. Thus, there has been both technological and social progress in the area of primary immunodeficiency. The future is clearly brighter each year. PMID- 2204269 TI - Evaluation of acute radiation optic neuropathy by B-scan ultrasonography. AB - We studied the accuracy of B-scan ultrasonography to diagnose radiation-induced optic neuropathy in 15 patients with uveal melanoma. Optic neuropathy was diagnosed by an observer masked as to clinical and photographic data. We analyzed planimetry area measurements of the retrobulbar nerve before and after irradiation. The retrobulbar area of the optic nerve shadow on B-scan was quantitated with a sonic digitizer. Increased optic nerve shadow area was confirmed in 13 of 15 patients who had radiation optic neuropathy (P less than .004). The correct diagnosis was confirmed when the results of ultrasound were compared to fundus photography and fluorescein angiography. In 13 patients there was acute radiation optic neuropathy. Two patients did not show an enlarged retrobulbar optic nerve, and the clinical appearance suggested early progression to optic atrophy. Ultrasonography documents the enlargement of the optic nerve caused by acute radiation changes. PMID- 2204270 TI - Histologic study of eyes with transsclerally sutured posterior chamber intraocular lenses. AB - We studied the postmortem histologic characteristics of two eyes that had undergone penetrating keratoplasty and transscleral suturing of a posterior chamber intraocular lens for bullous keratopathy. The eyes were studied three days postoperatively in a 79-year-old man with pseudophakia and six months postoperatively in an 83-year-old man with aphakia. We also removed a posterior chamber intraocular lens in a 73-year-old woman who had an epithelial downgrowth three months postoperatively. In the first two cases, only one of four haptics was successfully positioned in the sulcus. Histologic study disclosed a thin fibrous capsule surrounding the haptics at their attachment site, no inflammation around the transscleral portion of the suture, and exposure of a suture tip externally. In the third case, the intraocular lens fell back into the vitreous cavity after the fixation sutures were cut externally at the time of surgical removal. Stability of the lens in all three cases was primarily a result of intact transcleral sutures and not fibrous encapsulation or ciliary sulcus placement of haptics. PMID- 2204271 TI - Near syncope and chest tightness after administration of apraclonidine before argon laser iridotomy. PMID- 2204272 TI - Use of the argon laser to avoid complications from incomplete removal of corneal sutures with deeply buried knots. PMID- 2204273 TI - Cryptococcal keratitis after keratoplasty. PMID- 2204274 TI - The vasopressin-regulated urea transporter in renal inner medullary collecting duct. AB - The terminal part of the inner medullary collecting duct (terminal IMCD) is unique among collecting duct segments in part because its permeability to urea is regulated by vasopressin. The urea permeability can rise to extremely high levels (greater than 100 x 10(-5) cm/s) in response to vasopressin. Recent studies in isolated perfused IMCD segments have established that the rapid movement of urea across the tubule epithelium occurs via a specialized urea transporter, presumably an intrinsic membrane protein, present in both the apical and basolateral membranes. This urea transporter has properties similar to those of the urea transporters in mammalian erythrocytes and in toad urinary bladder, namely, inhibition by phloretin, inhibition by urea analogues, saturation kinetics in equilibrium-exchange experiments, and regulation by vasopressin. The urea transport pathway is distinct from and independent of the vasopressin regulated water channel. The increase in transepithelial urea transport in response to vasopressin is mediated by adenosine 3',5'-cyclic monophosphate and is associated with an increase in the urea permeability of the apical membrane. However, little is known about the physical events associated with the activation or insertion of urea transporters in the apical membrane. Because of the importance of this transporter to the urinary concentrating mechanism, efforts toward understanding its molecular structure and the molecular basis of its regulation appear to be justified. PMID- 2204275 TI - Synaptic mechanisms regulating cardiovascular afferent inputs to solitary tract nucleus. AB - This brief review summarizes recent electrophysiological studies concerning the initial processing of cardiovascular afferent inputs within the central nervous system. This work has shown that the site of termination of baroreceptor afferent fibers, the nucleus of the tractus solitarius (nTS), is much more than a simple relay station. Interactions between afferent inputs from different reflexogenic areas and interactions that depend on the timing of the afferent inputs can influence the output of nTS neurons in either an inhibitory or facilitatory manner and thereby determine the signal that these neurons relay to subsequent central nuclei involved in cardiovascular regulation. In addition, descending inputs from more rostral structures (e.g., the hypothalamic defense area and the parabrachial nucleus) can further alter the responsiveness of nTS neurons to baroreceptor inputs. The evidence suggests that the neural substrates exist for a modulation of baroreflex gain at an early stage in the reflex pathway. PMID- 2204276 TI - Effect of positive end-expiratory pressure on hypoxic pulmonary vasoconstriction in the dog. AB - We studied the effects of uni- and bilateral positive end-expiratory pressure (PEEP) on pulmonary artery pressure-flow (Ppa/Q) relationships during unilateral hypoxia in anesthetized dogs. A bronchial divider was inserted, the right lung was ventilated with 100% O2, and the left lung was ventilated with either 100% O2 (hyperoxia) or a hypoxic gas mixture (hypoxia). Left lung blood flow (QL) and aortic flow (QT) were measured by electromagnetic flow probes. Simultaneous Ppa/Q relations for both lungs, with Q on the ordinate, were obtained by altering QT via an arteriovenous fistula and an inferior vena cava occluder. Ppa/Q slopes (delta Q/delta Ppa) and extrapolated zero-flow Ppa intercepts (Pzf) were obtained by linear regression analysis. Bilateral PEEP increased Pzf for both lungs (P less than 0.01) but did not alter delta Q/delta Ppa of either lung. Unilateral PEEP decreased ipsilateral blood flow (P less than 0.001) and increased Pzf for the ipsilateral lung (P less than 0.05). Left lung PEEP did not affect the slope of the left lung Ppa/Q relationship (delta QL/delta Ppa). Hypoxic ventilation of the left lung decreased QL (P less than 0.001), increased Pzf (P less than 0.05), and decreased delta QL/delta Ppa (P less than 0.001). Neither uni- nor bilateral PEEP altered this flow diversion away from the left lung or the reduction in delta QL/delta Ppa with left lung hypoxia. We conclude that PEEP and alveolar hypoxia increase pulmonary vascular resistance at different loci, such that their effects are additive. A net increase in 10 cmH2O of PEEP does not inhibit the pulmonary vascular response to regional alveolar hypoxia. PMID- 2204277 TI - Prostaglandins mediate skeletal muscle arteriole dilation in hyperdynamic bacteremia. AB - Live Escherichia coli bacteremia during the high cardiac output (hyperdynamic) phase of sepsis causes constriction of large arterioles but dilation of small arterioles in skeletal muscle. This study examines the role of dilator prostaglandins, serotonin, and histamine in these differential microvascular responses in the decerebrate rat that avoids the effects of drug anesthesia. Topical application of meclofenamate, a prostaglandin synthesis inhibitor, to the cremaster muscle 60 min after induction of E. coli bacteremia enhanced the constriction of large arterioles from 20 +/- 8 to 46 +/- 9% less than baseline and blunted the dilation of small arterioles from 39 +/- 9 to 17 +/- 7% above baseline values in the cremaster microcirculation. Induction of E. coli bacteremia after pretreatment of the cremaster with meclofenamate constricted large arterioles to 40 +/- 4% less than baseline and small arterioles to 31 +/- 4% less than baseline. This indicates that prostaglandins initiate small arteriole dilation in response to E. coli, but some other dilator factor is activated by prostaglandins to maintain small arteriole dilation during E. coli bacteremia. Topical application of cyproheptadine, an antagonist of both histamine and serotonin receptors, to the cremaster muscle did not alter the E. coli-induced constriction of large arterioles or the dilation of small arterioles in the cremaster microcirculation. PMID- 2204278 TI - Direct evidence of changes in myofilament responsiveness to Ca2+ during hypoxia and reoxygenation in myocardium. AB - In the presence of 1 microM ryanodine, muscles loaded with the calcium indicator aequorin were stimulated at 15-20 Hz to produce steady levels of force and intracellular Ca2+ concentrations [( Ca2+]i) at various extracellular Ca2+ concentration ([Ca2+]o). After 5, 10, and 15 min of hypoxia and 3 min of reoxygenation, tetani were initiated. Force vs. [Ca2+]i relation was shifted to the right 0.11, 0.18, and 0.24 pCa units, and maximal force was down 66, 48, and 37% after start of hypoxia. During reoxygenation, the relationship was shifted up by 26%. In skinned fiber preparations, an increase in inorganic phosphate ion concentration from 0 to 10 mM and 15 mM decreased maximal force development by 32 and 53%, respectively, and shifted the pCa-force curve to the right by 0.08 and 0.14 pCa. A decrease in pH from 7.1 to 6.8 shifted the pCa-force curve to the right by 0.20 pCa units without affecting maximal force. These changes indicate that during hypoxia, a decrease in the sensitivity of the myofilaments to Ca2+ and a depression of maximal Ca2(+)-activated force occur, whereas during reoxygenation, there is an increase in maximal Ca2(+)-activated force. PMID- 2204279 TI - Assessment of muscle blood flow by laser-Doppler flowmetry during hemorrhage in SHR. AB - Skeletal muscle blood flow was assessed via laser-Doppler flowmetry (LDF) in the gracilis muscle of anesthetized 12- to 15-wk-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) control rats subjected to graded hemorrhage. Tissue perfusion was assessed at 20 specific sites in the muscle before and 20 min after each of five successive 1-ml withdrawals of blood. Mean LDF signals recorded from the gracilis muscle of SHR and WKY were similar during the prehemorrhage control period. After hemorrhage, mean arterial pressure and calculated vascular resistance of the gracilis muscle were higher in SHR than in WKY, and SHR exhibited a greater reduction of LDF signal in response to hemorrhage than WKY. Although SHR and WKY had a similar number of low flow sites (LDF signal less than 0.17 V) during the control period, successive blood volume withdrawals led to a significantly greater increase in the number of poorly perfused areas in the muscles of the hypertensive animals. The results of this study suggest that LDF is a useful tool to assess tissue perfusion during circulatory stress and that hemorrhage causes a greater decrease in skeletal muscle blood flow in SHR than in WKY. More severe reductions in tissue perfusion may contribute to the reduced ability of hypertensive animals to survive after hypotensive hemorrhage. PMID- 2204281 TI - Effects of antiglucocorticoid RU 486 on development of obesity in obese fa/fa Zucker rats. AB - The effects of RU 486 (mitepristone), an antagonist of type II glucocorticoid receptors (GR), on the development of obesity in young 5-wk-old obese fa/fa rats has been investigated. After 15 days of treatment, body composition of obese RU 486-treated rats was similar to that of lean-vehicle rats. Analysis of body composition changes showed that RU 486 effectively reversed the obesity. It stopped fat deposition in obese rats but increased protein deposition to the level of lean-vehicle rats. RU 486 prevented the development of hyperphagia and reduced gross energetic efficiency in the obese rats but had little effect on lean rats. Brown adipose tissue mitochondrial GDP binding was increased in obese rats but was reduced in lean rats by RU 486 treatment. RU 486 also reduced the elevated activity of hippocampal glycerophosphate dehydrogenase, a glucocorticoid responsive enzyme, of obese rats to the level of lean rats. The evidence suggests that abnormal activity of glucocorticoid GR receptors or abnormal cellular responsiveness to corticosterone receptor complexes may be important in the development of obesity in the fa/fa rat. PMID- 2204280 TI - Effects of glucoprivation on gastric motility and pituitary oxytocin secretion in rats. AB - Pharmacological doses of insulin (3-25 U/kg sc) elicited feeding and increased gastric motility in rats. In contrast, the glucose analogue 2-deoxy-D-glucose (2 DG), given ip in doses known to increase food intake, had dose-dependent effects on gastric motility: 100 and 200 mg/kg 2-DG increased gastric motility, whereas 500 mg/kg 2-DG virtually eliminated gastric contractions. This latter result resembled the known effects on gastric motility of cholecystokinin (CCK) and LiCl. Moreover, like CCK and LiCl, 500 mg/kg 2-DG stimulated pituitary oxytocin (OT) secretion, and its effects on gastric motility and OT secretion were potentiated by pretreatment with the opioid antagonist naloxone. In contrast, OT secretion was not affected by insulin-induced hypoglycemia with or without naloxone pretreatment. These results suggest that there are two components to the effects of 2-DG on gastric motility: an insulin-like excitatory component and a CCK-LiCl-like inhibitory component. The latter inhibitory component may be mediated by the paraventricular nucleus of the hypothalamus, which has already been implicated in the inhibitory control of gastric motility. PMID- 2204282 TI - Beta-cell hyperresponsiveness: earliest event in development of diabetes in monkeys. AB - Diabetes develops spontaneously in some, but not all, obese middle-aged monkeys. Longitudinal study of spontaneously obese rhesus monkeys has now shown the separation in time of the onset of various abnormalities associated with non insulin-dependent diabetes mellitus (NIDDM). Glucose tolerance and acute and late insulin release were assessed at 6-mo to 1-yr intervals over a period of 7 yr in six young, lean, normal animals and 14 middle-aged obese, initially normoglycemic monkeys. Over 2-5 yr, while under study, five of the obese subjects developed overt diabetes [fasting plasma glucose greater than 140 mg/dl and decreased glucose disappearance rates (KG) less than 1.5]. Progressively increasing hyperinsulinemia leading to a 10-fold increase in basal plasma insulin levels (mean +/- SE = 443 +/- 69 microU/ml) and a fivefold increase in insulin response to glucose occurred independent of degree of obesity and before hyperglycemia. Later, basal and stimulated insulin levels declined before significant hyperglycemia. We conclude that in the monkey beta-cell function is clearly enhanced, not reduced, in the earliest stages of the progression to NIDDM but is reduced just before overt diabetes. PMID- 2204283 TI - Effects of baroreceptor denervation on endocrine and drinking responses to caval constriction in dogs. AB - Plasma arginine vasopressin (AVP), plasma renin activity (PRA), and water intake (H2OIN) are increased by thoracic inferior vena caval constriction (TIVCC). To assess the role of the cardiac and sinoaortic baroreceptors in these responses, 9 sham-, 10 cardiac-(CD), 6 sinoaortic-(SAD), and 4 combined cardiac and sinoaortic (CD + SAD) denervated conscious dogs were studied. All animals were studied while normally hydrated 1) with no access to water (H2O-) and 2) while drinking was permitted (H2O+). TIVCC caused similar reductions (P less than 0.001) of mean arterial (-32 +/- 4 mmHg), left atrial pressure (-6.5 +/- 1.1 cmH2O), and right atrial pressure (-4.2 +/- 0.8 cmH2O) in all groups. After TIVCC in sham dogs with H2O-, AVP increased from 3.6 +/- 0.7 to 72.8 +/- 12.6 pg/ml (P less than 0.001). AVP was similar with SAD (57.1 +/- 6.9) but was reduced with CD (30.9 +/- 3.0) and CD + SAD (17.7 +/- 4.0). In all groups, PRA increased from 4.5 +/- 0.7 to 23.8 +/- 3.0 ng.ml-1 x 3 h-1 and plasma angiotensin II (ANG II) increased from 14.0 +/- 2.8 to 59.5 +/- 13.0 pg/ml (P less than 0.001). Plasma adrenocorticotropic hormone (ACTH) increased similarly in all groups (55 +/- 5 to 128 +/- 25 pg/ml). Plasma norepinephrine (NE) levels increased similarly in all groups (298 +/- 61 to 654 +/- 88 pg/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2204284 TI - [Anatomo-functional characteristics of hemodynamics in the mother-placenta-fetus system]. PMID- 2204285 TI - [Possible use of acoustic stimulation in the evaluation of fetal condition]. PMID- 2204286 TI - [Morphological characteristics of ultrasonic studies of the stages of placental maturity in physiological pregnancy]. AB - A sonographic and morphological study of placentas in 307 pregnant women has yielded histological criteria for sonographic staging of the placenta. In addition, sonographic estimates of uteroplacental and placental circulation were obtained. Simplicity and informativeness of these criteria make them recommendable for extensive use in practical health care. PMID- 2204288 TI - [Fetal liver volume: a method of its measurement by ultrasonics and its changes in the second half of uncomplicated pregnancy]. AB - A method has been developed for estimation of the fetal liver volume by ultrasound measurement of its every lobe. A proportionality coefficient of ultrasound sizes and volumes of the lobes were obtained by studies in 23 in utero fetal deaths. Findings on the liver volumes in 218 normal fetuses with gestational ages of 20 to 40 weeks were compiled as percentile curves. The right lobe of the fetal liver was found to have a greater size than the left one while the dead fetuses showed an inverse ratio. PMID- 2204287 TI - [Use of the method of immunothermistography in obstetrical practice]. AB - This paper presents results of testing pregnant women for staphylococcal antigen sensitization using immunothermistography (ITG). The ITG is based on registration of environmental heat conduction change with a microthermistor resistor during antigen-antibody reaction. The study group comprised 75 pregnant women immunized by staphylococcal anaphylotoxin and nonimmunized pregnant and nonpregnant women. Blood alfa-antistaphylolysin levels showed a close direct correlation with ITG findings. Combined use of these methods identified a population of pregnant women requiring immunization. PMID- 2204289 TI - [Various aspects of the trigger mechanisms of labor]. PMID- 2204290 TI - The Alaska Railroad Hospital and its last superintendent, Fred Braun. PMID- 2204291 TI - A nasty case of frostbite on Kodiak Island (1808). PMID- 2204292 TI - Suggested state legislation: Nursing Practice Act, Nursing Disciplinary Diversion Act, Prescriptive Authority Act. PMID- 2204293 TI - Review of current techniques for the verification of the species origin of meat. AB - An overview of developments that have occurred in meat species identification over the last decade is presented. It starts by noting the different requirements for speciation techniques over the period, describes the complex nature of meat in terms of chemical composition and shows how the chain of events from slaughter to retail gives rise to opportunities for deliberate adulteration or innocent contamination. The limitations of techniques such as electrophoresis and isoelectrofocusing are pointed out where the analysis of mixed meats is concerned; attention then focuses on the range of techniques based on antigen antibody interactions: agar gel immunodiffusion, counter immuno-electrophoresis and enzyme-linked immunosorbent assay (ELISA) in three formats. The choice of analyte is discussed, firstly for the analyses of raw meat materials and secondly, for heat-processed meat products. In the first example, blood serum proteins are used almost exclusively despite the limitation that their presence does not necessarily denote the presence of the corresponding muscle tissue (meat). For cooked products, a new range of antisera are necessary, based on thermally stable components derived from the tissues. By using different formats of ELISA, it is demonstrated that different responses can be obtained for heat processed meat versus processed offal, and that determination of a species meat content in a cooked mixed meat product is possible. Techniques for improving the specificity and performance of antisera are discussed briefly, with the future introduction of thermally stable, muscle-specific monoclonal antisera being seen as the way forward. PMID- 2204295 TI - [Methods of x-ray diagnosis of the adult respiratory distress syndrome]. PMID- 2204294 TI - Local cerebral glucose utilization in the neocortical areas of the rat brain. AB - The neocortex of the rat brain can be subdivided into regions of different local cerebral glucose utilization (LCGU). However, only a few neocortical areas can be delineated by differences in mean LCGUs between neighbouring areas. These area borders correspond exactly with cytoarchitectonically defined borders found in adjacent Nissl-stained preparations. On the other hand, nearly all of the architectonically defined area borders are also recognizable in the LCGU pictures, if differences in laminar distribution patterns of LCGU are taken into account. Furthermore, interareal differences in mean LCGU mainly reflect changes in layer IV, whereas layers II-III and V-VI show nearly identical LCGU values in all neocortical areas of the rat brain. The primary sensory areas exhibit the highest LCGU in layer IV, while the primary motor cortex shows a high LCGU in layer V. As the cytoarchitectonically defined pattern of the cortex is generally corroborated by the regional and laminar LCGU distribution, anatomical, metabolic and functional aspects of cortical architecture are associated. PMID- 2204296 TI - [Catecholamines and adrenergic receptors]. PMID- 2204297 TI - Glucose tolerance and insulin response in normal-weight and obese cats. AB - Glucose tolerance and insulin response were evaluated in 9 normal-weight and 6 obese cats after IV administration of 0.5 g of glucose/kg of body weight. Blood samples for glucose and insulin determinations were collected immediately prior to and 2.5, 5, 7.5, 10, 15, 30, 45, 60, 90, and 120 minutes after glucose infusion. Baseline glucose concentrations were not significantly different between normal-weight and obese cats; however, mean +/- SEM glucose tolerance was significantly impaired in obese vs normal-weight cats after glucose infusion (half time for glucose disappearance in serum--77 +/- 7 vs 51 +/- 4 minutes, P less than 0.01; glucose disappearance coefficient--0.95 +/- 0.10 vs 1.44 +/- 0.10%/min, P less than 0.01; insulinogenic index--0.20 +/- 0.02 vs 0.12 +/- 0.01, P less than 0.005, respectively). Baseline serum insulin concentrations were not significantly different between obese and normal-weight cats. Insulin peak response after glucose infusion was significantly (P less than 0.005) greater in obese than in normal-weight cats. Insulin secretion during the first 60 minutes (P less than 0.02), second 60 minutes (P less than 0.001), and total 120 minutes (P less than 0.0003) after glucose infusion was also significantly greater in obese than in normal-weight cats. Most insulin was secreted during the first hour after glucose infusion in normal-weight cats and during the second hour in obese cats. The impaired glucose tolerance and altered insulin response to glucose infusion in the obese cats was believed to be attributable to deleterious effects of obesity on insulin action and beta-cell responsiveness to stimuli (ie, glucose). PMID- 2204298 TI - Synovial fluid pH, cytologic characteristics, and gentamicin concentration after intra-articular administration of the drug in an experimental model of infectious arthritis in horses. AB - Chemical and cytologic effects and bactericidal activity of gentamicin in septic synovial fluid were evaluated in an experimental model of infectious arthritis in horses. Septic arthritis was induced by inoculation of approximately 7.5 X 10(6) colony-forming units of Escherichia coli into 1 antebrachiocarpal joint in each of 16 clinically normal adult horses. Clinical signs of septic arthritis were evident 24 hours after inoculation. Horses were allotted to 3 groups: group-1 horses (n = 5) each were given 150 mg of gentamicin (50 mg/ml; 3 ml) intra articularly (IA); group-2 horses (n = 5) each were given 2.2 mg of gentamicin/kg of body weight, IV, every 6 hours; and group-3 horses (n = 6) each were given buffered gentamicin, consisting of 3 mEq of sodium bicarbonate (1 mEq/ml; 3 ml) and 150 mg of gentamicin (50 mg/ml; 3 ml), IA. Synovial fluid specimens were obtained at posttreatment hour (PTH) 0, 0.25, 1, 4, 8, 12, and 24 via an indwelling intra-articular catheter. Synovial fluid pH was evaluated at PTH 0, 0.25, and 24. Microbiologic culture and cytologic examination were performed on synovial fluid specimens obtained at PTH 0 and 24, and gentamicin concentration was measured in all synovial fluid specimens. At PTH 0, E coli was isolated from synovial fluid specimens obtained from all horses. Synovial fluid pH was lower (range, 7.08 to 7.16) and WBC count was higher (range, 88,000 to 227,200 cells/microliters) and predominantly neutrophilic (95 to 99%) at PTH 0 than before inoculation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2204300 TI - Ultrasonographic-anatomic correlation and imaging protocol for the spleen in anesthetized dogs. AB - Sonographic and/or anatomic observations were made of the spleen in 27 dogs. Anatomic studies were used to establish precise correlations between the gross anatomic features of the organ and its ultrasonographic image. In 8 anesthetized dogs, ultrasonographic images of the spleen were made in dorsal, transverse, and sagittal planes. When it was incident to the ultrasonic beam, the splenic capsule was represented by a fine echogenic line that defined the boundaries of the organ. The splenic substance had a uniformly mottled echogenicity apart from the anechoic lumen of the splenic venous rami, which were detected at and near the hilus of the spleen. Less regularly, splenic arterial rami were detected at the hilus, but not within the splenic substance. Dorsal and transverse images were made with the ultrasonic transducer perpendicular to the left thoracic and abdominal wall at the 11th intercostal space and caudoventrad to it. Sagittal images were produced with the transducer's face directed craniad, placed parallel to the left lateral abdominal wall, and pushed under the costal arch. The adoption of such an ultrasonographic imaging protocol ensures that all of the spleen is inspected. A definitive opinion can then be given as to whether the spleen is normal or abnormal. Pathologic changes in the spleen must also be differentiated from changes in adjacent organs or structures. PMID- 2204299 TI - Bovine recombinant granulocyte-macrophage colony-stimulating factor enhancement of bovine neutrophil functions in vitro. AB - Neutrophils were purified from blood of dexamethasone-treated (0.04 mg/kg of body weight) and untreated calves. Cells were untreated (controls) or cultured in media containing 5 or 10 ng of bovine recombinant granulocyte-macrophage colony stimulating factor (rbGM-CSF)/ml for 10 to 12 hours before being tested for various functions. Dexamethasone treatment of calves decreased luminol-dependent chemiluminescence, decreased phagocytosis of Pasteurella multocida and several Staphylococcus spp by various degrees, and decreased antibody-dependent cell mediated cytotoxicity against bovine herpesvirus-infected cells by 26 to 32%. The percentage phagocytosis of coagulase-positive S aureus and S intermedius was higher than that of coagulase-negative S epidermidis for neutrophils from all calves. Culture of neutrophils with rbGM-CSF significantly increased (P less than 0.05) all of the aforementioned functions, compared with control neutrophils; however, rbGM-CSF-induced increases in function tended to be higher in neutrophils from dexamethasone-treated calves than in neutrophils from untreated calves. PMID- 2204302 TI - Vascular injury following foreign body perforation of the esophagus. Review of the literature and report of a case. AB - Esophageal perforation resulting from foreign body ingestion is a rare occurrence. Most of the complications associated with this event, such as retroesophageal abscess, mediastinitis, pericarditis, pneumothorax, and pneumomediastinum, are widely recognized. However, little attention has been directed to the possibility of vascular injury caused by the perforating object. Isolated case reports have described significant morbidity and mortality subsequent to major vascular trauma resulting from an esophageal foreign body, usually emphasizing the presence of a "signal" hemorrhage from the gastrointestinal tract as a key to diagnosis. This report describes a case of esophageal perforation caused by an ingested fishbone that resulted in significant aerodigestive hemorrhage, possibly as the result of an unusual isolated vascular injury. The literature on vascular trauma following foreign body perforation of the esophagus is reviewed, and suggestions for the diagnosis and treatment of these dreaded complications are made. PMID- 2204301 TI - Bronchial foreign bodies: an uncommon way of entry. AB - The author describes two cases of bronchial foreign bodies that were not inhaled. One of them was found in the right lower bronchus after having penetrated through a wound in the chest wall. The other was lodged in the right main bronchus after penetration through a wound in the soft tissue of the neck. Both foreign bodies were successfully removed with the bronchoscope. PMID- 2204303 TI - Diagnosis and management of cleft larynx. Literature review and case report. AB - Laryngeal cleft is a rare congenital laryngeal anomaly that has been recognized more frequently in recent years. It can be a serious problem, consisting of separation of the arytenoids with a fissure resulting from a defect in the fusion of the posterior cricoid cartilage lamina. Dysphagia with aspiration of food is commonly seen with resultant bouts of pneumonia. Surgical repair has been successful in a handful of cases. This communication will review our institution's recent handling of a case successfully treated. The epidemiology, embryology, classification, diagnosis, and suggested treatment regimen for laryngeal cleft will also be outlined. PMID- 2204304 TI - Computerized tomographic analysis of orbital hypertelorism repair: spatial relationship of the globe and the bony orbit. AB - Computerized tomographic scans provide a new means of evaluating the spatial and geometric relationships between the movement of the bony orbit and its soft tissue contents (the globe and extraocular muscles) [1, 12]. Preoperative and postoperative computerized tomographic scans were analyzed in four patients to explore these relationships. Measurement of the changes in distance between the globes correlated most closely with the change in the distance between the lateral orbital walls; resection of medial (inter-orbital) bone provides space into which the globe is translocated. The medial rectus muscle may be bowed across the medial wall osteotomy line, creating a functional shortening of the muscle; this finding may explain the esotropia that is commonly seen after this procedure [2, 3]. These observations should have a direct impact on the understanding and planning of orbital hypertelorism correction. PMID- 2204305 TI - Prevention of enophthalmos: a hypothesis. PMID- 2204306 TI - Merkel cell carcinoma: the clinical course. AB - Merkel first discovered the cells named after him in the snout skin of voles in 1875. These cells are thought to originate from the neural crest and act as mechanoreceptors. When they have undergone malignant change, the neurosecretory granules in the cytoplasm may release various polypeptides, suggesting that the tumor is an APUDoma. In a computer search of the literature 121 cases were identified. It was revealed that the most common lesion is an erythematous nodule arising in the face or lower limb and occurring predominantly in women in their late 60s. The regional nodes became involved in half the patients, and the three year survival was approximately 60%. Two unusual cases, in women 72 and 73 years old respectively, with metastasizing lesions that responded to a combination of surgery and radiotherapy are reported, and the literature is discussed. PMID- 2204307 TI - Systemic lupus erythematosus associated with antiribosomal P protein antibody. AB - Three patients with systemic lupus erythematosus had positive antiribosomal P protein antibodies. The patients are women who had mild diseases that did not involve prominent internal organs. By using an immunofluorescence method for the detection fo antinuclear antibodies that employs HEp-2 cells, these serum samples produced intense stainings on cytoplasm and nucleoli that were digested with RNase. With the use of an immunoblotting technique, these serum samples recognized three ribosomal P proteins, called PO (38 kd), P1 (19 kd), and P2 (17 kd). We suggest that antiribosomal P protein antibodies can be detected in patients with systemic lupus erythematosus and associated mild clinical features. PMID- 2204308 TI - Scleroderma following augmentation mammoplasty. Report of a case and review of the literature. AB - A 46-year-old woman developed localized scleroderma after surgical manipulation of her silicone gel-filled breast prostheses. She developed firm, shiny plaques on her legs that progressed to involve the thighs. Histopathologic examination of a deep-skin biopsy specimen confirmed the diagnosis of scleroderma. On surgical removal of the silicone implants, and their replacement with saline-filled implants, the scleroderma gradually resolved. Histopathologic examination of the removed implant capsules revealed evidence of silicone leakage. All new female patients with scleroderma should be questioned and examined regarding augmentation mammoplasty. Until prospective studies are completed on the possible association between scleroderma and silicone breast implants, it would seem prudent to use the saline-filled, elastomeric envelope-type breast implant for augmentation mammoplasty rather than the silicone gel-filled implant. PMID- 2204309 TI - Refractory bullous pemphigoid leading to respiratory arrest and successfully treated with plasmapheresis. PMID- 2204311 TI - American Nephrology Nurses' Association. Chapter presidents. PMID- 2204310 TI - Necrotizing vasculitis at granulocyte-macrophage-colony-stimulating factor injection sites. PMID- 2204312 TI - Does aluminium have a pathogenic role in dialysis associated arthropathy? PMID- 2204313 TI - Antigen induced arthritis in beige (Chediak-Higashi) mice. AB - Mice with the beige mutation, which are known to be deficient for leucocyte elastase and cathepsin G, were used to investigate the role of neutral proteases in a model for antigen induced arthritis. Surprisingly, it was shown that in this model of arthritis, using methylated bovine serum albumin as an antigen, C57/black/6 'beige' mice (deficient for leucocyte neutral proteases) developed a more severe form of arthritis than the control mice ('black' mice), resulting in a higher degree of tissue damage. The incidence and degree of bone apposition and destruction of articular cartilage at day 21 after induction of arthritis were significantly higher in the beige mice. These findings could not be ascribed to differences in the cellular immune response to methylated bovine serum albumin. Autoradiographic detection of radiolabelled methylated bovine serum albumin suggested that more antigen is retained in the joints of beige mice than in black mice, which might account for the sustained arthritis and the concomitant tissue damage. These findings do not support the contention that leucocyte elastase and cathepsin G contribute to the pathogenesis of joint destruction in this model. PMID- 2204314 TI - Inflammatory bowel disease and ankylosing spondylitis associated with cutaneous vasculitis, glomerulonephritis, and circulating IgA immune complexes. AB - Two patients both with inflammatory bowel disease (IBD) and ankylosing spondylitis (AS) developed leucocytoclastic vasculitis of the skin and nephropathy. Immunofluorescence studies showed that there was perivascular deposition of immunoglobulin A in the skin biopsy specimens of both patients and in the renal mesangium of one patient. Serum samples of the two patients contained IgA immune complexes. The absence of previous reports on such a combination of symptoms in IBD or AS suggests that these patients may have a disease entity which is distinct from uncomplicated IBD or AS, and which may combine the immunopathological features of both underlying disorders. PMID- 2204315 TI - Neurogenic influences in arthritis. PMID- 2204316 TI - The evolution of techniques and indications for lung transplantation. AB - The techniques and indications for lung transplantation have evolved significantly in the past 6 years. We initially restricted single-lung transplantation to patients with pulmonary fibrosis and developed the double-lung transplantation procedure for patients with emphysema or cystic fibrosis. However, with the double-lung procedure, a 25% mortality rate resulted from ischemic complications at the tracheal anastomosis. The technique was altered to incorporate bilateral bronchial anastomosis, with a resulting reduction in airway complications. The double-lung transplantation procedure continued to have significant drawbacks, including intraoperative and postoperative hemorrhage, and cardiac complications due to prolonged cardiopulmonary bypass, ischemic cardiac arrest, and extensive manipulation of the heart. These problems recently have been addressed with a much simplified procedure incorporating a bilateral transverse thoracosternotomy, replacement of the right lung without cardiopulmonary bypass, and replacement of the left lung with or without a short period of partial bypass. This procedure has been successfully used for emphysema and for cystic fibrosis. The technique of single-lung transplantation also has been simplified and indications have been expanded to include selected patients with emphysema and with primary pulmonary hypertension. With single-lung transplantation, each of the lungs from a donor has been successfully used for a separate recipient on several occasions, improving the supply of available donor organs. PMID- 2204318 TI - The specific functions of menaquinone and demethylmenaquinone in anaerobic respiration with fumarate, dimethylsulfoxide, trimethylamine N-oxide and nitrate by Escherichia coli. AB - The respiratory activities of E. coli with H2 as donor and with nitrate, fumarate, dimethylsulfoxide (DMSO) or trimethylamine N-oxide (TMAO) as acceptor were measured using the membrane fraction of quinone deficient strains. The specific activities of the membrane fraction lacking naphthoquinones with fumarate, DMSO or TMAO amounted to less than or equal to 2% of those measured with the membrane fraction of the wild-type strain. After incorporation of vitamin K1 [instead of menaquinone (MK)] into the membrane fraction deficient of naphthoquinones, the activities with fumarate or DMSO were 92% or 17%, respectively, of the activities which could be theoretically achieved. Incorporation of demethylmenaquinone (DMK) did not lead to a stimulation of the activities of the mutant. In contrast, the electron transport activity with TMAO was stimulated by the incorporation of either vitamin K1 or DMK. Nitrate respiration was fully active in membrane fractions lacking either naphthoquinones or Q, but was less than or equal to 3% of the wild-type activity, when all quinones were missing. Nitrate respiration was stimulated on the incorporation of either vitamin K1 or Q into the membrane fraction lacking quinones, while the incorporation of DMK was without effect. These results suggest that MK is specifically involved in the electron transport chains catalyzing the reduction of fumarate or DMSO, while either MK or DMK serve as mediators in TMAO reduction. Nitrate respiration requires either Q or MK. PMID- 2204319 TI - [Proprioceptive reflexes and the regulation of movement]. AB - Apart from the direct influences of muscle spindle sensory endings on skeletomotor neurones a great deal of their reflex drive is provided indirectly via the gamma-loop. Fusimotor neurones modulate their discharge rate in parallel with that of the skeletomotor neurones during the rising phase, as well as during the maintained reflex tension in m.triceps surae of decerebrated cat, when small tension oscillations are present in the muscle. However, under other conditions of spinal reflex activities either skeletomotor or fusimotor neurones could be activated independently by impulses from muscle receptors. On the ground of the presented results, it can be supposed that fusimotor firing, together with the afferent firing from muscle spindles, does not provide the main stimulus for the reflex activity of skeletomotor neurones but serves as an indicator of the deviations from the expected or planned movement representing, in this way, its model. PMID- 2204317 TI - The role of graft-derived dendritic leukocytes in the rejection of vascularized organ allografts. Recent findings on the migration and function of dendritic leukocytes after transplantation. AB - Dendritic cells isolated from lymphoid tissues are potent stimulators of primary allogeneic T-cell responses in vitro and in vivo. Similar major histocompatibility complex class II-bearing dendritic-shaped leukocytes are contained within transplanted organs and these are thought to be important passenger leukocytes that trigger rejection. Recent findings on the migration, phenotype, and function of cardiac dendritic leukocytes (DLs) are reviewed. After transplantation donor DLs migrate rapidly from mouse cardiac allografts into the recipients's spleens. Within the spleens donor DLs associate with recipient CD4+ T cells. Isolated cardiac DLs, like lymphoid dendritic cells, are potent stimulators of T-cell proliferation in vitro. This suggests that DLs function as passenger leukocytes by migrating from grafts into the lymphoid tissues of the recipient and that sensitization to vascularized organ allografts may occur centrally within lymphoid tissues rather than peripherally in the graft itself. PMID- 2204320 TI - [Legislation regarding safety in the work environment and the handling of toxic substances in the 19th century and the beginning of the 20th century]. AB - The paper deals with selected occupational safety and health regulations in Croatia in the last century and at the beginning of this century, which aimed at protecting the worker in crafts, industry, on farms and in various other occupations against the effects of toxic and other noxious substances and against injury at the workplace. Regulations relating to health protection of the general population from the adverse effects of particular substances are also discussed. Toxic metals (e.g. lead, copper, tin, arsenic) were to be found in various types of pottery or in the colouring matter for use in foodstuffs and drinks as well as in dyes used in the manufacturing of toys, paints and wall-paper. Apart from sporadic decisions and legal actions organized occupational health care was non existent at that time. Laws and regulations concerning protection from occupational and non-occupational hazards came into force progressively, with developing knowledge about beneficial and adverse features of various substances in human use. PMID- 2204321 TI - [Cell-differon organization of the tissues and the problem of wound healing]. AB - Problems on correlation of processes of normal histogenesis and those of physiological and reparative regeneration are discussed. A special attention is paid to the cellular-differon organization of tissue and its significance for understanding cellular mechanisms and ultrastructural bases in tissue regeneration after lesions and use of biostimulators of various origin. Certain peculiarities have been revealed in changes of intra- and interdifferon interrelations of cells in various tissues at regenerative histogenesis. The biostimulators applied differently change duration and manifestation of its stages, that is they influence the internal structure of the process and the cellular-tissue composition of the regenerate. PMID- 2204323 TI - [English anatomist and physician Nathaniel Highmore (on his 375th birthday)]. PMID- 2204322 TI - [General principles of the development of the thyroid gland in lemmings from the Vrangel island in the dynamics of the population cycle]. PMID- 2204324 TI - [Phenotypic variants of the smooth-muscle cells in an atheromatous plaque of the human aorta]. AB - The authors investigated the expression of cytoskeletal proteins and the ultrastructure of cells in normal intima and atheromatous plaque of human aorta. It has been established, using double immunofluorescent method and a set of antibodies that intimal smooth muscle cells /SMC/ of normal aorta express myosin, vimentin, alpha-actin and actin but not desmin. In seven out of 28 atherosclerotic plaques the cells contained desmin and all other SMC cytoskeletal proteins were found. These cells had the ultrastructural features of SMC, i.e. well-developed endoplasmic reticulum and Golgi apparatus. Besides, some cells in 13 atherosclerotic plaques proved to be myosin-, alpha-actin- and desmin negative. The cells were stained with monoclonal antibodies specific to SMC but not with macrophage-specific antibody. Ultrastructurally, the cytoplasm of the cells was filled with rough endoplasmic reticulum and a developed Golgi complex, but a certain portion of the cells retained basal lamina and myofilament bundles. The peculiarities of cytoskeletal protein in expression and ultrastructure of cells in human aortic atherosclerotic plaques may be explained by a phenotypic modulation of vascular SMC. PMID- 2204325 TI - [The basic features of the pathogenesis of pseudotuberculosis (yersiniosis)]. AB - A new pathogenetic pattern of pseudotuberculosis has been derived on the basis of original clinical, anatomical and experimental findings as well as literature data. Careful consideration is given to: a basic mode of infection (alimentary), emergence of the primary affection with a rapid blood invasion by the agent (primary bacteremia), development of specific sensitization, multiorgan secondary focal impairment with lymphogenic dissemination of the infective agent (specific pseudotuberculous polyadenitis), formation of secondary immunodeficiency, consequent repeat bacteremias, recurrences, symptoms of infectious process aggravations, immunological rearrangement with dominating delayed hypersensitivity. As a rule, the disease terminated by elimination of the secondary foci and recovery. PMID- 2204326 TI - [Embedding of tissue in celloidin-paraffin using acetone]. AB - The suggested technique allows obtaining large slices of hard tissues such as human skin. Replacement of ethanol for acetone improves quality of histological preparations and decreases their cost. PMID- 2204328 TI - [The centenary of the first Siberian department of pathological anatomy]. PMID- 2204327 TI - [Compensatory reactions--a special class of phenomena]. AB - The necessity of distinguishing the compensatory reactions as a special class of phenomena discovered by the author among all protective and adaptive processes is substantiated. The signs distinguishing compensatory reactions from physiological types of adaptation are presented. The rule is established that reflects an inevitable change in the type of live substrate functioning after the physiological regimen is switched to the compensatory one: when structural and functional deficiency develops in a system the principle of its functioning shifts from the balanced form (the function is brought about by a small number of perfectly working elements) to an extensive one (the function is brought about by many elements, each of them working with errors). PMID- 2204329 TI - [Early stomach cancer: its morphology, histo- and morphogenesis]. AB - Macroscopic, histologic and ultrastructural features of an early stomach carcinoma are presented on the basis of literature and the authors' data. Ultrastructural and immunohistochemical data confirm the concept of a common histogenesis of different histologic types of stomach carcinoma, i.e. from reserve cells. Carcinoma, most likely, develops from reserve cells of the foveolate epithelium and metaplastic epithelium of intestinal type (foci of incomplete intestinal metaplasia with sulfomucine secretion). The data are accumulating on the precancerous nature of severe epithelial dysplasia. The development of an early carcinoma from preexisting dysplasia was observed in patients after long follow-up with repeated gastric biopsies. PMID- 2204330 TI - A continuing controversy: magnesium sulfate in the treatment of eclamptic seizures. AB - It would appear from the above that Pritchard agrees with the use of some agents other than magnesium sulfate that have known anticonvulsant properties. We believe that the subject at issue is whether magnesium sulfate should be used in treating the seizures of eclampsia. In our "Controversies" article, we do not address the issue of whether magnesium sulfate modifies pathophysiological factors leading to preeclampsia, but restrict ourselves to the treatment of the seizure per se, once seizures supervene, and the avoidance of their recurrence. The pathophysiological mechanisms and optimal treatment of preeclampsia and of eclampsia (excepting seizures) remain to be determined, as does the use of magnesium sulfate in this condition. Eclamptic seizures are clinically and electroencephalographically indistinguishable from generalized tonic-clonic seizures. Whether seizures arise in or out of the setting of preeclampsia, they should be treated as are other seizures, with known anticonvulsants. Controlled clinical trials are needed to address the effectiveness of alternative antiseizure regimens. PMID- 2204331 TI - Positron emission tomography in Creutzfeldt-Jakob disease. AB - Regional cerebral glucose metabolism was studied in a 73-year-old woman with autopsy-confirmed Creutzfeldt-Jakob disease, using positron emission tomography of 2-(18F)fluorodeoxyglucose. Regional absolute values were analyzed in 14 partially overlapping slices. Clinically, the patient was in an advanced stage of disease when positron emission tomographic scans revealed severe, diffuse hypometabolism, and neuropathological findings showed diffuse spongiform changes throughout the brain, with neuronal cell loss being obvious only in the cerebellum. Computed tomography was unremarkable for age, whereas the positron emission tomographic results were in accordance with histological findings and the patient's clinical condition. This article suggests that positron emission tomography depicts neuronal dysfunction rather than neuronal cell loss. PMID- 2204332 TI - Transcranial Doppler ultrasonography of the middle cerebral artery in the hemodynamic assessment of internal carotid artery stenosis. AB - We performed transcranial Doppler ultrasonography of the middle cerebral arteries in 43 patients who underwent cerebral angiography. Twelve patients had normal arteriograms, 18 had internal carotid artery stenosis, and 13 had complete occlusion. Parameters measured included: flow velocity (mean, maximum, and peak systolic), flow acceleration, systolic-to-diastolic ratio, and pulsatility index. Patients with 75% to 100% stenosis had lower average ipsilateral flow acceleration and mean velocity than did normal subjects. Correlation analysis revealed an inverse relationship between degree of stenosis and ipsilateral flow acceleration, as well as ipsilateral mean velocity. These correlations were no longer significant when we excluded normals, however. There was a linear relationship between right and left velocity values for both normal subjects and patients with occlusion but not for patients with stenosis. This technique has potential for the reliable assessment of the hemodynamic effect of carotid stenosis on intracranial circulation. PMID- 2204333 TI - Interpleural catheter for analgesia after cholecystectomy: the surgical perspective. AB - Sixteen otherwise healthy women undergoing cholecystectomy were randomized to receive postoperative analgesia either by continuous infusion of papaveretum (n = 8), or by continuous interpleural infusion of bupivacaine (n = 8). Postoperative pain was assessed by linear analogue and ventilatory capacity. Changes in body protein were measured by in vivo neutron activation analysis. Clinical course was also noted. Pain scores were significantly lower in the interpleural group over the first 48 h (P less than 0.02). Ventilatory capacity was also significantly better for the first 24 h (P less than 0.025). There was no evidence of shortened postoperative ileus; hospital stay and postoperative fatigue were similar for the two groups. Weight and protein losses over a 2 week period were similar in the two groups. It is concluded that the apparent advantages in patient comfort and mobility offered by interpleural infusion are most marked in the first 48 h postoperatively, with an advantage in ventilatory capacity over the first 24 h. PMID- 2204334 TI - Spontaneous bacterial peritonitis in a healthy adult male. AB - A 44-year-old man was admitted with acute abdominal pain, anorexia, nausea and dry retching, with tenderness and rigidity of the abdominal wall. Exploratory laparotomy revealed generalized peritonitis. He developed delerium tremens soon after operation and dehiscence of the abdominal wound 36 hours postoperatively. When the wound was closed and reinforced his recovery was uneventful. This case was unusual because he did not have ascites or cirrhosis, which are commonly associated with the disease. PMID- 2204335 TI - Assessment and treatment of sex offenders: the Prince of Wales Programme. AB - The treatment programme for sex offenders at the Prince of Wales Hospital, Sydney, is described. Penile circumference assessment is not used as there is no evidence it provides a valid measure of individuals' paedophile or rapist tendencies. Sex offenders' self-reports remain the major source of information in their assessment. The development of the two major techniques used--imaginal desensitization and short-term medroxyprogesterone--is outlined. About 80% of subjects can be expected to show a good response to one or other of these therapies. Of those who do not, most respond to the alternative or aversive therapy. Adolescent offenders appear to require more intensive treatment. Results appear comparable with those of more intensive programmes in use overseas. PMID- 2204336 TI - Using a socio-historical frame to analyse aboriginal self-destructive behaviour. AB - The last two decades have seen rapid changes in many facets of Aboriginal society, including morbidity and mortality. The same period has witnessed a dramatic increase in writing about and by Aborigines and this has necessitated a re-examination of the national "history" to include the indigenous people of Australia. Medical workers in Aboriginal Australia should be alert to the historical forces determining patterns of ill-health. Psychiatry in particular must develop this perspective if it is to participate with Aborigines in addressing emergent patterns of behavioural distress including suicide, parasuicide, ludic behaviour and self-mutilation. This paper demonstrates the importance of the socio-historical frame in the examination of these behaviours from one discrete region in isolated Aboriginal Australia: the Kimberley. PMID- 2204337 TI - Intensive neurodiagnostic monitoring in psychiatry. AB - A series of technological advances have made it possible to closely monitor electrophysiological and behavioural manifestations of episodic clinical events over prolonged periods of time, with the ability to review the records at leisure or to submit them to computer analysis. The more promising techniques are time locked video/EEG monitoring, cable telemetry, radiotelemetry, ambulatory cassette recording, intensive plasma anti-epileptic drug monitoring and continuous neuropsychological monitoring. The greatest promise of these techniques is for the diagnosis, research and management of epilepsy. For psychiatry, they offer additional help in the differential diagnosis of non-epileptic events from epilepsy, the most important of which are psychogenic seizures and episodes of aggression. This paper discusses the potential role of these techniques in the assessment of non-epileptic events and transient cognitive impairment in clinical psychiatry. PMID- 2204338 TI - The effectiveness of services and treatment in psychogeriatrics. AB - The future development of new psychogeriatric services in Australia may well depend upon the demonstration of their potential effectiveness and efficiency. Descriptive accounts of effective services provide ample guidelines, although formal evaluation is lacking. Examining the major psychiatric disorders of the elderly shows that most are functional. Effective acute psychiatric treatment is available for these. In dementia cases, effective therapies exist for the reduction of secondary behavioural disabilities in the sufferer and the stress on carers. Adequately resourced comprehensive psychogeriatric services would be best equipped to deliver such treatments. PMID- 2204339 TI - Alcohol and the elderly. AB - Alcohol abuse and dependence are the third most common psychiatric diagnoses in elderly men in the community, occurring in 3% over the age of 65. Elderly patients may present in a number of atypical guises to medical, social, psychiatric and forensic services. When they do, their alcohol problem is often missed. They have high rates of physical morbidity and are most often found in the general hospital setting. While there is a steady decline in consumption and alcohol-related problems with age, up to a third of elderly abusers take up drinking in late life, possibly in response to psychosocial stressors. Recognition has been a major barrier to effective management. Intervention studies point to difficulties in attracting patients to treatment, with little consensus on treatment regimes or goals. Given these problems, a regionally based service responsible for identifying and managing alcohol abuse in the elderly is proposed. Such a service could improve liaison with community and hospital-based programmes and allow practical research to be undertaken into this enigmatic problem. PMID- 2204341 TI - The organization of open complexes between Escherichia coli RNA polymerase and DNA fragments carrying promoters either with or without consensus -35 region sequences. AB - Transcription initiation at the Escherichia coli galP1 promoter does not depend on specific nucleotide sequences in the -35 region. Footprint analysis of transcriptionally competent complexes between E. coli RNA polymerase and DNA fragments carrying galP1 shows that RNA polymerase protects sequences as far upstream as -55, whereas sequences around the -35 region are exposed. In contrast, with galP1 derivatives carrying -35 region sequences resembling the consensus, RNA polymerase protects bases as far as -45, and the -35 region is fully protected. Taken together, our data suggest that the overall architecture of RNA polymerase-promoter complexes can vary according to whether or not consensus -35 region sequences are present; in the absence of these sequences, open complex formation requires distortion of the promoter DNA. However, the unwinding of promoter DNA around the transcription start is not affected by the nature of the -35 region sequence. With a galP1 derivative carrying point mutations in the spacer region that greatly reduce promoter activity, the protection of bases by RNA polymerase around the -10 sequence and transcription start site is reduced. In contrast, protection of the region upstream of -25 is unaffected by the spacer mutations, although sequences from -46 to -54 become hypersensitive to attack by potassium permanganate, indicating severe distortion or kinking of this zone. We suggest that, with this galP1 derivative, RNA polymerase is blocked in a complex that is an intermediate on the path to open complex formation. PMID- 2204342 TI - Identification, sequencing and expression of an integral membrane protein of the trans-Golgi network (TGN38). AB - Organelle-specific integral membrane proteins were identified by a novel strategy which gives rise to monospecific antibodies to these proteins as well as to the cDNA clones encoding them. A cDNA expression library was screened with a polyclonal antiserum raised against Triton X-114-extracted organelle proteins and clones were then grouped using antibodies affinity-purified on individual fusion proteins. The identification, molecular cloning and sequencing are described of a type 1 membrane protein (TGN38) which is located specifically in the trans-Golgi network. PMID- 2204344 TI - Cardiovascular disease risk factor reduction and the occupational health nurse. AB - The occupational health nurse should be attuned to issues and research regarding prevention of CVD. Risk reduction programs in industry should adhere to the recommendations of groups such as the Adult Treatment Panel of the National Cholesterol Education Program, the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure, and the American Health Association. Despite significant reductions in CVD mortality, continued research is needed to further our knowledge of CVD risk factors among high risk populations. PMID- 2204343 TI - Pilot study on the therapeutic efficacy, clinical safety, and dosage finding of enciprazine in out-patients with anxious and anxious-depressive syndromes. AB - The new basic propanolamine derivative enciprazine (D 13 112) was tested in an open single-blind phase-II trial with regard to therapeutic efficacy, clinical safety, and dosage finding. The drug showed a good efficacy in mildly ill patients. Under the highest dosage frequently fatigue was reported. In 78% of the patients the enciprazine trial succeeded in shifting patients from benzodiazepines to non-benzodiazepines or in discontinuation of psychopharmacotherapy after completion of the trial. PMID- 2204340 TI - Protein folding. PMID- 2204346 TI - Accelerated synthesis and release of angiotensin II in the rat brain during electroacupuncture tolerance. AB - Behavioural studies suggested that cerebral angiotensin II (AII) plays an important role in the development of tolerance to electroacupuncture (EA) analgesia. Observations made in this study revealed an increase in AII immunoreactivity (AII-ir) in both CSF and brain as well as an increase in the cerebral content of AI-ir in rats rendered tolerant to EA. The extracts of brain from rats receiving EA for 1h and 3h were subjected to gel filtration and the elution profile was compared with that of normal brain extract. There was a marked right shift of the AII peak from the large molecule precursor to the small molecule AII-ir. The latter peak showed the same retention time in HPLC system as that of AII. The results suggest that the acceleration of the synthesis and release of AII during a long-term EA stimulation might constitute one of the mechanisms for EA tolerance. PMID- 2204347 TI - [Gene expression regulation of adipocyte differentiation: cell cycle and hormones]. AB - The adipose conversion of cultured preadipose cells involves the activation of numerous genes and is controlled by various adipogenic and mitogenic factors. The differentiation program can be divided into early and late events. Early events are triggered by growth arrest at the G1/S boundary and characterized by the activation of a set of genes (pOb24, lipoprotein lipase, etc.). The expression of the terminal differentiation-related genes takes place after a limited growth resumption of early markers containing cells and requires the presence of permissive hormones (growth hormone and triiodothyronine). Insulin acts solely as a modulator in the expression of the terminal differentiation-related genes. In vivo studies suggest that the acquisition of new adipocytes might result from terminal differentiation of dormant, already committed (pOb24 positive) cells when exposed to appropriate mitogenic or adipogenic stimuli. PMID- 2204345 TI - Cellular immunity to human insulin in individuals at high risk for the development of type I diabetes mellitus. AB - In order to investigate the role of insulin as a potential target autoantigen of cellular immunity in the prediabetic period, proliferative responses of T lymphocytes to human insulin were studied in nine islet-cell antibody (ICA) + first-degree relatives of patients with Type I diabetes (individuals at high risk for the development of Type I diabetes, or the 'prediabetic' group, which was never treated with insulin) and in 12 control individuals. Insulin autoantibodies were present in 6/9 (67%) of the prediabetic subjects and none of the controls. Peripheral blood lymphocytes were collected on Ficoll and incubated with human insulin, control antigens, or media alone for 5-6-day and 9-10-day incubation periods. Cells were pulsed with 3H-thymidine, harvested, and analysed in a scintillation counter. Results are expressed as stimulation index (SI = cpm with antigen/cpm without antigen), with a SI greater than or equal to 1.5 considered a positive response. Eight of nine (89%) prediabetic individuals responded positively to insulin after a 9-10-day incubation period, in contrast to four of 12 (33%) control subjects, P less than 0.05. The mean proliferative response to insulin after 9-10 days' incubation was 2.1 +/- 0.4 and 1.2 +/- 0.1, for the prediabetic and control groups, respectively. The proliferative response to insulin was not directly correlated with levels of insulin autoantibodies (r = 0.05, NS). These data suggest that most individuals at high risk for the development of Type I diabetes display a cellular immune response to insulin, and a subset of these individuals does not display a concomitant humoral immune response to insulin based on the presence or absence of insulin autoantibodies. PMID- 2204348 TI - [Decrease of gene expression of glycerophosphate dehydrogenase by dexamethasone in differentiated 3T3-F442A cells: antagonism with insulin and antiglucocorticoid RU38486]. AB - Preadipocyte subclones derived from mouse 3T3 cells differentiate into adipocytes; this differentiation is characterized by an increased activity of numerous enzymes required for triglyceride synthesis and/or mobilization. Among these enzymes, the role of glycerophosphate dehydrogenase in the differentiation process has been previously reported. In the present work, we studied the hormonal regulation of glycerophosphate dehydrogenase gene expression (G3PDH) in differentiated 3T3-F442A adipocytes. Dexamethasone (DEX) elicited a 50% decrease in both mRNA content and specific activity of G3PDH. This effect was due to a posttranscriptional event since DEX shortened the half life of the mRNA, whereas it did not modify the transcription rate of this gene. The DEX effect is specific to G3PDH, since the expression of another adipose-specific gene, namely adipsin, is not modified by DEX treatment. Insulin counteracts the inhibitory effect of DEX, mainly by stabilizing the mRNA encoding for G3PDH. The antiglucocorticoid RU38486 is able to reverse DEX inhibition. Latter phenomenon suggests that DEX action on G3PDH gene expression could be mediated by glucocorticoid receptors. PMID- 2204349 TI - Modulation of sulfated proteoglycan synthesis and collagen gene expression by chondrocytes grown in the presence of bFGF alone or combined with IGF1. AB - Prepubertal rabbit epiphyseal chondrocytes were grown in high density primary culture for 3 d. They were then incubated for 3 additional d in serum-free culture medium to which bFGF (1-50 ng/ml) was added. During the last 24 h incubation period, either IGF1 (1-80 ng/ml) or Insulin (1-5 micrograms/ml) was added to the culture medium. Chondrocyte DNA was significantly augmented with the increasing concentration of bFGF used, thus confirming its mitogenic effect on chondrocytes. On the other hand, bFGF was also shown to modulate the phenotypic expression of the chondrocytes. The 35S-sulfate incorporation into newly synthesized proteoglycans by the cultured cells decreased in a dose-dependent manner with bFGF concentration used. In addition, chondrocyte collagen gene expression was also shown to be modulated by bFGF. Total RNA extracted from the cultured cells was analyzed by dot blot and Northern blot with cDNA probes encoding for alpha 1 II and alpha 1 I procollagen chains. A significant lower level of type II collagen mRNA, the marker of chondrocytic phenotype, was observed when cells were grown in the presence of bFGF while the level of type I mRNA remained unchanged. When IGF1 or a high concentration of insulin was added to the cells during the last 24 h of incubation with bFGF, sulfated proteoglycan synthesis, as well as collagen type II mRNA level, were significantly stimulated when compared with chondrocytes incubated with bFGF alone. In conclusion, in the present experimental conditions, bFGF appears to be a growth promoting agent for chondrocytes in vitro with dedifferentiating action on chondrocyte phenotype. IGF1 or insulin used at a high concentration can prevent the dedifferentiating effect of bFGF without inhibiting its stimulating effect on chondrocyte DNA synthesis. PMID- 2204350 TI - [Oncogene cooperation in cellular transformation]. AB - Oncogenic cell transformation induces major changes in the structure and physiology of the cells: modifications of morphology, differentiation block, disorganisation of cytoskeleton and extracellular matrix, alterations in growth control. The identification of oncogenes relies upon transfer into host normal cells of DNA isolated from cancer cells. The recent development of DNA transfer into germinal cells has provided new insights into the genetic control of tumorogenesis in vivo. In most cases, full transformation into leukemic or tumor cell requires the cooperation of several oncogenes. These observations support the hypothesis of cancer as a multistep process. However, many of the cooperative oncogenes have not yet been identified, especially in human cancers. The recent discovery of genes acting as repressors of cell growth in normal cells has brought to light a new class of potential recessive oncogenes that might have a contributory function in cancer development. PMID- 2204351 TI - Humoral immunity to Candida albicans (anti-candida antibody titers) in premature infants. AB - Although the role of humoral and cell mediated immunity in neonatal defense against candida infections is not precisely defined, one of the contributing immunologic factors may be a lack of decreased specific passive humoral immunity. Thus, serum samples from the umbilical veins of 98 term gestation and 105 premature neonates (majority less than 33 wk gestation) and their mothers (n = 100) were tested for the presence of hemagglutinating antibodies to commercially available candida antigen. The titers of candida antibodies (mean log2 +/- SEM) were significantly higher in 11 term neonates (4.73 +/- 0.69) of mothers with high antibody titers (5.18 +/- 0.40, less than 0.001) as contrasted with 87 normal term (2.38 +/- 0.15) and 105 premature (2.87 +/- 0.15) infants with normal mothers (1.96 +/- 0.13 and 3.31 +/- 0.26, respectively). Contrary to our belief 81% of term infants and all of the preterm infants (majority less than 33 wk gestation) had passive specific anti-candida antibody titers less than 1:16. PMID- 2204352 TI - Human trophoblast cells in culture express an unusual major histocompatibility complex class I-like antigen. AB - We present evidence that the trophoblast cells obtained from first trimester placentae by a culture method developed in our laboratory express a class I-like HLA antigen that is only sparsely distributed on the cell surface, lacks classical polymorphic determinants, and consists of heavy chains of lower molecular weight than those of classical HLA in association with beta 2 microglobulin (beta 2M). The latter two features are in general agreement with a previous report describing the nature of the HLA molecule on trophoblast disaggregated from term amniochorion. These cultured trophoblast cells could be useful for molecular studies of the unusual class I antigen, as well as for other in vitro experiments designed to mimic the in vivo local trophoblast-uterine interactions. PMID- 2204353 TI - Calcitonin gene-related peptide-LI in subarachnoid haemorrhage in man. Signs of activation of the trigemino-cerebrovascular system? AB - Calcitonin gene-related peptide (CGRP) is a neurotransmitter candidate together with the tachykinins in sensory fibres in the cerebral vasculature, with possible vasodilating properties. The origin of most of the CGRP-immunoreactive cerebrovascular nerve fibres seems to be the trigeminal ganglion. Experimentally produced vasoconstriction in cats after lesions of the trigeminal ganglion have shown marked prolonged constriction compared to controls. The possible involvement of the trigemino-cerebrovascular system as a defence system, with CGRP probably being the more potent vasodilatator, was investigated in 12 patients with subarachnoid haemorrhage (SAH). After operation with clipping of the aneurysm and treatment according to department policy, blood samples were taken from the external jugular vein on postoperative days 1, 2, 3, 5, 7, 9, frozen and analysed (radioimmunoassay) for CGRP-LI (-like immunoreactivity) levels. The patients were monitored with Doppler recordings from the middle cerebral arteries (MCA) and internal carotid arteries (ICA) following blood sampling. The relationship Vmean MCA/V mean ICA was used as an index of vasospasm. The highest CGRP-LI levels were found in the patient with highest velocities/index values. In patients with MCA aneurysms (n = 7), a correlation of r = 0.61 was found between the index and CGRP-LI levels. However, significant changes in the group as a whole was not found. The possible involvement of the trigemino-cerebrovascular system in SAH is discussed. PMID- 2204354 TI - A low cost modification of an old Leksell stereotactic frame to allow CT-guided stereotaxy. AB - The high cost of commercial CT-compatible stereotactic frames has restricted the availability of CT-guided stereotaxy for many neurosurgical centres. However, many of these centres do possess the standard stereotactic frames for projection radiography, of which the old type Leksell frame is probably the most common. We have devised a simple and low-cost modification to an old Leksell frame to allow CT-guided stereotaxy. The nature of the modifications allow complete freedom of positioning of the frame relative to the CT scanner and coordinate transformations can be performed simply and effectively. The modified frame has been used successfully for some 18 months and the modification has now been performed at two centres in the North West Regional Health Authority. We hope this modification will allow many other centres to embark on CT-guided stereotaxy. PMID- 2204355 TI - Sex differences among oxytocin-immunoreactive neuronal systems in the mouse hypothalamus. AB - Serial frontal sections of male and female mouse hypothalamus were immunostained with an antiserum to oxytocin, in order to study the topographical distribution of oxytocinergic perikarya and processes. Numbers of immunostained perikarya were counted in various hypothalamic regions. The oxytocin content of microdissected hypothalamic tissue samples was measured in radioimmunoassays. While the overall topographical distribution of oxytocin neurons in the classical magnocellular nuclei was similar in both genders, quantitative differences could be observed. The numbers of immunostained perikarya and the amounts of oxytocin found in females exceeded by far the numbers and amounts found in males. Male mice had fewer oxytocin-immunostained axons, projecting within the brain, than females. This was especially apparent in parts of the limbic system. Oxytocin immunostained neurons in the perifornical region, the lateral hypothalamus and the ventral ansa lenticularis were mostly absent in males. It is possible that the observed sex differences in oxytocin immunoreactive brain architecture are due to the different hormonal conditions in males and females. PMID- 2204357 TI - Bibliography of the current world literature. PMID- 2204356 TI - The response of noradrenergic axons to systemically administered DSP-4 in the rat: an immunohistochemical study using antibodies to noradrenaline and dopamine beta-hydroxylase. AB - The response of noradrenaline (NA) axons to the effects of systemic injections of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) was studied in the rat brain. Antibodies to NA and to dopamine-beta-hydroxylase (DBH) were employed to assess by immunohistochemistry the effects of DSP-4 on NA axons between 6 h and 2 weeks after drug administration. The changes in NA and DBH staining after DSP-4 treatment were restricted to brain regions innervated by the locus coeruleus. In these areas, DSP-4 induced profound loss of both NA and DBH from NA axons, but with a distinctly different time-course. While NA disappeared within hours after drug treatment, DBH staining of NA axons remained unchanged during the first 4 days after DSP-4 treatment. Thereafter, there was an abrupt loss of DBH staining which coincided with the appearance of numerous brightly stained, thick and swollen NA axons. The distribution of these fibres suggests that they represent the distal ends of preterminal NA axons. Two weeks after drug treatment, NA axons could no longer be visualized by either NA or DBH immunohistochemistry in regions affected by DSP-4. During this 2-week time-period, the staining of cell bodies in the locus coeruleus and of ascending NA axons in the dorsal bundle was unaffected. The results suggest two phases in the response of NA axons to DSP-4: an acute phase, marked by loss of transmitter, and a neurodegenerative phase, characterized by loss of DBH and structural disintegration of NA axons. PMID- 2204358 TI - The risk of transmission of HIV-1 through non-percutaneous, non-sexual modes--a review. AB - To date, three well-documented modes of transmission of HIV-1 (sexual, percutaneous and perinatal) have been described. Although the theoretical possibility exists for HIV-1 transmission through other routes, including non percutaneous, non-sexual modes often referred to as 'casual' contact (and several anecdotal reports suggest this possibility), there is no credible epidemiological evidence to support this. Fourteen combined surveys, with over 750 individuals with potential exposure through non-percutaneous, non-sexual modes of contact, have failed to find a single case of HIV-1 infection (upper bound of 95% confidence interval = 0.40%), indicating that the risk of transmission by non percutaneous, non-sexual modes is remote. Given the emotionally charged concerns about transmission of an infection which may end fatally in a high proportion of affected individuals, critical review of the low probability of transmission through non-percutaneous, non-sexual modes is important so that preventive efforts can be focused appropriately. PMID- 2204359 TI - Vitamin B12 injections in patients treated with zidovudine. PMID- 2204360 TI - Mitral valve prolapse vs mitral valve prolapse syndrome: what is the difference? PMID- 2204361 TI - Studies of NADP(+)-preferred secondary alcohol dehydrogenase from Thermoanaerobium brockii. AB - Alcohol dehydrogenase has been purified from the cell-free preparation of Thermoanaerobium brockii to homogeneity, employing combined DEAE, Sephadex, and affinity chromatographic procedures. The enzyme is tetrameric having subunit molecular weight of 40.4 x 10(3). The purified alcohol dehydrogenase is capable of utilizing either NAD+ or NADP+ to oxidize primary and secondary alcohols, although it prefers NADP+ as the coenzyme and secondary alcohols as substrates. Inactivation of the enzymic activity by sensitized photooxidation and carboxymethylation implicates the presence of catalytically important histidine and cysteine residues. Kinetic studies indicate that Thermoanaerobium alcohol dehydrogenase catalyzes NADP(+)-linked oxidations of secondary alcohols by an ordered bi-bi mechanism with NADP+ as the leading reactant. The preference of the Thermoanaerobium enzyme for NADP+ is correlated with its low dissociation constants (KA and KiA) and high turnover rate (V/Et). The corresponding kinetic parameters also contribute to the preference of this enzyme for secondary alcohols. PMID- 2204362 TI - [Comparative evaluation of Escherichia coli strains as markers for the study of bacteriophages]. AB - The count of coliphages in polluted waters was found to be dependent on many experimental factors. The host-strain used for their enumeration is among the most important. In this paper we report a comparative investigation on the variability of counts of coliphages in sewage as a result of variations in host strains of Escherichia coli and in methodologies. Two methods were used for enumerating them: the M.P.N. and the direct count. E. coli C, B1, Hfr and E36 consistently produced more plaques than any other host tested. PMID- 2204363 TI - Cell-mediated immune responses to soluble Plasmodium falciparum antigens in residents from an area of unstable malaria transmission in the Sudan. AB - This paper describes immune responses to P. falciparum infection in individuals living in an area of highly seasonal, unstable malaria transmission. The in vitro cellular immune responses of peripheral blood mononuclear cells (PBMC) from 36 Sudanese donors to a complex of affinity purified soluble P. falciparum antigens (SPag) and two components thereof (Ag1 and Ag7) were examined and compared to humoral immune parameters. In 29/36 Sudanese donors, SPag induced a significant lymphoproliferative response in vitro. In contrast only 3/27 Danish donors never exposed to malaria responded to SPag. Ag1 and Ag7 induced significant lymphoproliferation in 9/34 and 13/36 Sudanese donors respectively, whereas no Danish donors responded. Significant interferon-gamma production was observed in 16/27, 1/5 and 3/12 Sudanese donors when stimulated by SPag, Ag1 and Ag7 respectively. Lymphoproliferative responses to SPag correlated with proliferative responses to Ag1 and Ag7, and with Spag-induced interferon-gamma production. These results indicate that T-cell clones recognizing epitopes on Ag1 and Ag7 have been expanded in the studied population as a result of exposure to P. falciparum infection. The T-cell parameters did not correlate with the presence of antibodies to SPag, Pf155/RESA or a crude parasite sonicate or with the schizont IFA titers of the plasma. This indicates that parameters outside the degree of exposure to P. falciparum influence the cellular immune responses to malaria. PMID- 2204364 TI - Screening for autoantibodies in patients with primary fibromyalgia syndrome and a matched control group. AB - Primary fibromyalgia syndrome (PFS) is a non-articular rheumatic condition characterized by chronic muscular pain. We have performed screening for autoantibodies in 20 women with PFS and in 19 age-matched healthy women. Fifty five percent of the PFS patients had anti-smooth muscle antibodies and 40% had anti-striated muscle antibodies. None of the control subjects had any muscle antibodies. There was no significant difference in frequency of the remaining autoantibodies between the groups investigated. The present study indicates autoimmune responses in PFS against antigens of the diseased tissue itself, a finding which may be secondary to the disease or have relevance to the still obscure pathogenesis of the syndrome. PMID- 2204365 TI - Oesophagectomy for severe corrosive injuries: is it always legitimate? AB - Twenty total gastric resections were performed on 80 patients admitted to surgery for severe oesophagogastric corrosive injuries, with immediate or delayed full thickness necrosis or perforation of the stomach. The duodenum, cardia and cervicothoracic oesophagus were sutured. A cervical oesophagostomy and a feeding jejunostomy were done. The oesophagus was thus excluded. All the corrosive agents were liquid. The ingested quantities were higher than 150 ml in 11 cases. Oesophagoscopy was performed in 12 patients: 4 lesions were stage III, 5 stage II, 2 stage I, while in 1 the mucosa appeared normal. Five patients died, but only 1 from an oesophageal complication, an oesophago-tracheal fistula on the 33rd post-operative day. The survivors had a secondary colon bypass and 5 patients developed a secondary mucocele. We suggest that the low incidence of tracheo-oesophageal fistula in our series and the possible formation of a mucocele in the excluded oesophagus are two arguments for a conservative attitude towards the oesophagus in most cases of emergency gastric surgery for corrosive lesions. Immediate oesophagectomy adds another traumatic factor to the effects of the burns. A subsequent oesophagectomy should be contemplated during coloplasty to prevent the formation of a mucocele. PMID- 2204366 TI - Mediastinal lymph node staging with transesophageal echography in cancer of the lung. AB - Transesophageal echography (TEE) was used prospectively to study mediastinal lymph node enlargement in 23 patients with cancer of the lung. The findings were validated blindly by comparison with computed tomography (CT, n = 23) and pathological N classification after curative surgery (n = 9). Lymph nodes larger than 1 cm were defined as pathologically enlarged. In the upper mediastinum, 22% (8 vs 36), in the lower mediastinum including the subaortic region 112% (37 vs 33) and in the hilar region 67% (6 vs 9) of enlarged lymph nodes diagnosed by CT were detected by TEE. A pathological study in 9 patients demonstrated true positive findings in 2 vs 1, true negatives in 4 vs 5, false positives in 3 vs 2 and false negatives in 0 vs 1 comparing TEE with CT. From these preliminary data, we conclude that TEE, although still experimental, is equal or superior to CT in detecting enlarged nodes in the lower mediastinum, specifically in the aortopulmonary window but clearly inferior in the upper mediastinum and the hilar region. Additional information on central tumors and infiltration of the heart or great vessels can be clarified. In addition, data on hemodynamics and cardiac status can be obtained. TEE seems to be a promising tool in the preoperative staging of lung cancer. PMID- 2204368 TI - Human immunodeficiency virus infection in childhood: the disease and its cutaneous manifestations. PMID- 2204367 TI - Recruiting young adults in an urban setting: the Chicago CARDIA experience. AB - The recruitment goal of Chicago Coronary Artery Risk Development in Young Adults (CARDIA) was 1,100 randomly selected young adults, in equal proportions for men and women, blacks and whites, two age groups, and two education groups. CARDIA is an ongoing multicenter study of the health and lifestyles of young adults designed to trace the development of risk factors for coronary heart disease over time. Participants completed a four-and-one-half hour exam and agreed to return two years later. In Chicago CARDIA, one of the four centers in the national collaborative study, random digit dialing of computer-generated telephone lists was the initial recruitment technique. Initial recruitment efforts resulted in too few low-socioeconomic status (SES) white participants and too few blacks. In response the sampling procedure was modified to focus on census tracts with a high density of blacks, more low-SES whites, and convenient public transportation. By being flexible, Chicago CARDIA improved recruitment in certain hard-to-fill cells and achieved the overall goals: 1,109 participants, 50% black and 50% white, near equal proportions by sex and age, and close to the recommended 40%/60% spread on education. The Chicago experience should benefit others conducting research in an urban setting. PMID- 2204369 TI - Advances in pediculosis, scabies, and other mite infestations. PMID- 2204370 TI - Diseases of the nails in infants and children. PMID- 2204371 TI - The immunology of allergic contact dermatitis: the DNCB story. AB - The observations described here reveal several important aspects of the human immune system and its responses. The immune system is like most major physiologic systems in that it has tidy and predictable dose-response relationships. This applies both to the induction phase and also the elicitation or expression phase. There is thus a graded, dose-related increase in the magnitude of sensitization that applies throughout the range both of clinically detectable reactivity but also down to subclinical levels of response. It becomes possible to speculate about the kinetics of clonal expansion and the stage of the process at which specific T cells leave the lymph node to enter the circulation--the onset of clinical sensitivity. Additional stimulation to the system causes "boosting"- additional clonal expansion, already well known in the field of humoral immunology. Immune responsiveness appears to be normally distributed in the population, with one "tail" of the distribution containing "high responders" who are particularly susceptible to sensitization by environmental antigens. The high responder status reflects a propensity for increased activation of antigen specific T cells during the induction of the response. Interestingly, the slope of the challenge dose-response curve and hence the expression phase is the same as that for normal subjects. An important factor in the activation or induction of an immune response is the concentration of antigen per unit area. Our studies on the influence of area of application of antigen indicate that at very small areas, between 3 mm and 1 cm across, changing area and hence number of antigen bearing Langerhans cells may alter sensitization. Above a threshold or plateau level, changing the area makes very little difference, whereas change in the concentration per unit area, i.e., the number of antigen molecules per Langerhans cells, is a powerful determinant of sensitizing potency. We have not explored the upper limit of this phenomenon, i.e., maybe the relationship does not hold above a certain area or dose. The final series of observations showed that the application of antigen to skin pretreated with UVB or PUVA is followed by an absence of immunologic response. This state differs from that seen in mice in that it reflects a "failure" of activation of the immune system rather than a state of down-regulation or tolerance. Having established these ground rules, it will be possible to move on to a whole series of additional questions relating basic aspects of immunology to the applied areas of contact dermatitis. PMID- 2204372 TI - Skin surface touch print: review of indications and uses. PMID- 2204373 TI - Some psychosomatic aspects of psoriasis. AB - The contribution of psychosomatic factors toward the morbidity associated with psoriasis should be evaluated in the context of the patient's developmental stage and life situation. The skin, as a sensory organ, plays a critical role in an individual's physical and emotional growth in early life. The skin also plays an integral role as an organ of communication throughout life and greatly affects an individual's body image and self-esteem. If these factors are not taken into consideration, the morbidity associated with psoriasis may increase, or the patient may remain dissatisfied with treatment even in the face of clinically satisfactory treatment outcome. Some recent studies indicate that the adverse impace of psoriasis upon the quality of life can result in significant chronic stress, which may in turn exacerbate the psoriasis in a subgroup of patients. As disease-related stress is present in every patient to some degree, the dermatologist should regularly assess the psychosocial impact of the disease. Certain personality factors, such as a tendency to want the approval of others and difficulty with assertion of angry feelings, may make the patient with psoriasis more vulnerable to stress and contribute toward the stress reactivity of the disease. The presence of depression in psoriasis may modulate itch perception, exacerbate pruritus, and lead to difficulties with initiating and maintaining sleep. Helping the patient to develop assertiveness skills in addition to supportive psychotherapy may facilitate the patient's capacity to cope with the daily stresses associated with psoriasis. Treatment of depressive symptoms may prove to be a helpful adjunct in the management of pruritus and sleep difficulties in psoriasis. PMID- 2204374 TI - Neutrophilic dermatoses: noninfectious diseases characterized by the accumulation of neutrophils. PMID- 2204375 TI - Apoptosis. PMID- 2204376 TI - Hamartomas. AB - Hamartomas of the skin are tumor-like malformations of mature or nearly mature structures that are part of the normal structure of skin. The onset is usually at birth; however, it may be delayed until childhood or early adulthood. Hamartomas may occur on any part of the body and are sometimes linear and unilateral. Histologically, they may show an alteration of a single cell line or of multiple related cell lines. Some types of the hamartomas may be markers for underlying internal organ abnormalties, such as the epidermal nevus syndrome, the nevus comedonicus syndrome, or the organoid nevus syndrome. Some may be prone to develop various secondary benign or malignant tumors as in an organoid nevus. Hamartomas may occur as solitary, sporadic lesions unrelated to other conditions or as multiple lesions that are inherited as an autosomal trait. The latter are often associated with systemic abnormalites. Hamartomas such as Becker's pigmented hairy nevus appear to be inherited as an autosomal dominant trait, but the late onset and variable expression may be under hormonal influence. So far only tuberous sclerosis has been shown to be related to a specific chromosomal abnormality, mutant gene located on the long arm of chromosome 9. PMID- 2204377 TI - Immunosuppressive and cytotoxic drugs: uses in the dermatologic patient. AB - The agents discussed in this article have potential benefits to treat severe and otherwise recalcitrant disease and thus result in improved survival as well as an improvement in life-style. Table 6 lists the diseases that might be considered for treatment as well as the major side effects for each agent. However, closely linked to the efficacious effects of these agents are the potential toxicities. Prior to using any of these agents, the physician must be fully aware of both the potential benefit and the potential side effects. A full and complete discussion with the patient should also occur. Since patients often do not retain all the information given to them in this discussion, subsequent visits with the physician should reinforce the information. PMID- 2204378 TI - Cultured epidermal grafts in the treatment of leg ulcers. AB - Cultured epidermal grafts offer a major advance in the treatment of burns and other disabling skin wounds in which there are few other available treatments. Cultured allografts offer immediate availability, obviating skin biopsies. Theoretically, they could be grown in advance, cryopreserved, and stored in skin banks. They provide rapid coverage of wounds and produce prompt relief of pain and healing that continues for many weeks after the graft has been applied. Their mechanism of action has not been elucidated, but it seems likely that the allografted cells do not survive permanently and are gradually replaced by host epithelial cells. Release of growth factors by cultured allografts may contribute significantly to their wound healing properties. Whatever their mechanism of action, they promote rapid epithelialization at least in small chronic wounds. Especially for the elderly patient with nonhealing ulcers, they offer an alternative treatment option that is simple, painless, and noninvasive. PMID- 2204379 TI - Office photography. PMID- 2204380 TI - EMLA: a new topical anesthetic. AB - Eutectic Mixture of Local Anesthetics (EMLA) containing 5% lidocaine and prilocaine in a cream was found to give effective topical analgesia in normal and diseased skin, making it useful for superficial surgery and various other clinical procedures. To be effective, an adequate amount must be applied under occlusion and at the right time before the intervention. PMID- 2204381 TI - Silicone: a critical review. AB - The response of biologic systems to implanted foreign materials is subject to a lesion of variables. Each type of implant must be individually evaluated in a specific application and host. Pure DMPS polymer injected into subcutaneous tissues behaves in a specific and characteristic way. An analysis of the behavior of other types of implants in other applications will not necessarily reveal insights applicable to the behavior of liquid silicone. Most adverse case reports relate to injected fluids of unknown purity or identity used in inappropriate volumes in poorly chosen anatomical sites. It is ironic that pure DMPS in small volumes, a theoretically ideal combination, is so mistrusted. However, liquid silicone's sinful potential was easy to predict. It was cheap, available, easy to use, and, when injected in large volumes, produced instant and financially profitable results. Moreover, a welter of confusing titles, "authorized investigators" and "medical grade silicone" coupled with sensationally adverse reports detailing a criminal misuse of this modality led to draconian measures banning its use and made a meaningful analysis of true incidence and type of side effects following its use nearly impossible to assess. The advocates' position that liquid silicone is safe when used properly cannot be refuted. Only a handful of serious adverse reactions can be documented following its use; however, the concept that pure DMPS polymer can, even in expert hands, occasionally produce immunologically mediated adverse effects is equally irrefutable. This concept is supported by the following evidence: 1. Minor idiosyncratic and granulomatous reactions occurring in 1 in 10,000 are reported in association with a nidus of infection or as a consequence of allergic events. 2. At least one serious inflammatory reaction occurred in a patient afflicted with both autoimmune disease and concurrent infection. These reactions are best understood in the broader context of tissue responses to all classes of implanted foreign material, and they are most easily understood in the narrow context of autoimmune disease after injection of implantable paraffin, silicone, and possibly "silicone polymers." "Certain authors speculate that silicone acting as a primary antigen is not likely," however, silicone acting as an adjuvant associated with a subclinical infection as an antigen source may be the cause of adjuvant disease. A careful review of published anecdotal and personal experience involving the use of 350 centistoke pure dimethypolysiloxane fluid (liquid silicone) for soft tissue augmentation in small volumes (and in large volumes for facial hemiatrophy) suggests that the bias against its proper use is unfounded.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2204382 TI - Cellular pharmacology of cisplatin: perspectives on mechanisms of acquired resistance. AB - The interactions of cisplatin with DNA have been defined in sophisticated detail; however, the interactions of this drug with other components of the cell are less well understood. There is much interest in how cisplatin gets into cells, how it is transformed and inactivated, how it and its biotransformation products are effluxed from the cell, how the DNA damage is repaired, and how all of these processes can be modulated for therapeutic gain. Recent years have seen much progress toward defining the cellular pharmacology of cisplatin and, in the process, several mechanisms of acquired resistance to this drug have now been elucidated. PMID- 2204383 TI - Cytolytic effector cells against human tumors: distinguishing phenotype and function. AB - Activation and expansion of lymphocytes in vitro and their adoptive transfer to animal models have helped to elucidate mechanisms of tumor rejection and to define the cytolytic effector cells involved. Several cell types that exhibit antitumor activity have been described. These include natural killer cells, lymphokine-activated killer cells, cytolytic T cells, and tumor infiltrating lymphocytes. Here we discuss our present understanding of the origins of these cells and the phenotypic and functional properties by which they can be distinguished. PMID- 2204384 TI - An experimental analysis of cancer: role of ras oncogenes in multistep carcinogenesis. AB - Carcinogen-induced animal tumor models are invaluable resources for studies aimed at understanding the participation of ras oncogenes in multistep carcinogenesis. Mutationally activated ras oncogenes are frequently detected in chemically induced animal tumors. The nature of the mutations in ras oncogenes reflects the chemical specificity of the carcinogen, implying that the carcinogen interacts with ras sequences. In chemically induced rat mammary tumor models, ras activation is the earliest detectable change in the mammary gland cells following administration of the chemical. Further, expression of the tumorigenic phenotype of cells containing activated ras requires the cooperation of normal physiological factors that are active during puberty. PMID- 2204385 TI - Regulation of hemopoiesis by cytokines that restrict options for growth and differentiation. AB - Regulators of hemopoiesis are traditionally classified as belonging to two groups having antagonistic activities, that is, stimulators versus inhibitors. The majority of the so-called "inhibitory" molecules do not differ from stimulators in their biological activity since both are inducers of differentiation and consequent cell death. It is hypothesized that these cytokines operate during emergency situations (such as bacterial infections) in peripheral organs and bloodstream. Conversely, steady-state hemopoiesis in blood-forming organs is regulated by stromal factors that support stem cell renewal and direct cell positioning. Some of these stromal cell factors are lineage-specific inhibitors. It is proposed that hemopoietically active cytokines be called restrictions, since their function is to minimize the options available for the cell and thereby determine its growth and differentiation pathway. PMID- 2204386 TI - Molecular mimicry of growth factors by products of tumor viruses. PMID- 2204387 TI - Cancer therapy with combinations of biological response modifiers and cytotoxics: an update. AB - The pleiotropic effects of BRMs on cell function emerged as one of the more prominent themes at this conference. As we continue to learn more about the mechanisms of action of BRMs, it seems likely that this aspect of their biology will one day be used for therapeutic gain. Conceivably, by varying the dose and schedule of a single BRM, it may be possible to achieve very different therapeutic goals: alteration of cell surface antigens or receptors, modulation of the cytotoxic activity of chemotherapeutic agents, or stimulation/restoration of immune effector cell function after chemotherapy. Moreover, as amply illustrated by the work summarized here, BRMs will undoubtedly have an even broader therapeutic spectrum when used in combination with other modalities. PMID- 2204388 TI - Technologic advances in computed tomography and magnetic resonance imaging in the central nervous system. PMID- 2204389 TI - Advances in technique and technology in body computed tomography and magnetic resonance imaging. PMID- 2204390 TI - Technologic advances in pediatric applications of computed tomography and magnetic resonance imaging. PMID- 2204391 TI - Technologic advances in magnetic resonance imaging and spectroscopy for cardiovascular applications. PMID- 2204392 TI - Digital radiology and other technical innovations. PMID- 2204394 TI - Technologic advances in radiation protection and other diagnostic topics. PMID- 2204393 TI - Advances in radiopharmaceuticals for brain imaging with single-photon emission computed tomography. PMID- 2204395 TI - Noninvasive measurement of blood flow and perfusion. PMID- 2204396 TI - Noninvasive imaging of cardiac masses. PMID- 2204397 TI - Magnetic resonance imaging of congenital heart disease. PMID- 2204398 TI - Noninvasive evaluation of the pericardium and myocardium. PMID- 2204399 TI - Noninvasive imaging of thoracic aortic disease. PMID- 2204400 TI - Advances in interventional cardiology: coronary balloon angioplasty and alternative techniques. PMID- 2204401 TI - Advances in interventional cardiology: endomyocardial biopsy, valvuloplasty, and pediatric interventional cardiology. PMID- 2204402 TI - Technologic advances. PMID- 2204403 TI - Cardiac imaging. PMID- 2204404 TI - Staphylococcus aureus and Escherichia coli in nham (Thai-style fermented pork sausage). AB - The fate of Staphylococcus aureus and Escherichia coli was determined when they were introduced into ground pork made into nham (Thai-style fermented pork sausage) with or without 0.75 or 1.5% added starter culture. Without starter culture, the numbers of E. coli remained little changed but there was slow multiplication of S. aureus. With 0.75% starter culture, S. aureus was no longer detectable after 48 h and E. coli numbers decreased by 1 log after 96 h. No viable S. aureus or E. coli were recovered after 36 h and 96 h, respectively, when 1.5% starter culture was added. The addition of a starter culture is recommended when making nham. PMID- 2204405 TI - Growth and toxigenesis of C. botulinum type E in fishes packaged under modified atmospheres. AB - Modified atmosphere packaging of fresh fish is used to market high quality products in some European countries. The potential risk of C. botulinum growth in these extended shelf-life foods is still a concern; especially since toxigenesis may precede organoleptic spoilage. This paper will present toxigenic data from rockfish, salmon and sole muscle tissues which were inoculated with a pool of non proteolytic C. botulinum type E at seven levels (10(-2)-10(4) spores/sample), and stored under vacuum and 100% CO2, at incubation temperatures between 30 and 4 degrees C, for up to 60 days. Factorial experimental design allowed predictive formulae to be developed able to describe the lag time prior to C. botulinum toxigenesis and the probability of one spore to initiate toxigenesis based upon the storage conditions. Accurate characterization of the microbial ecology of C. botulinum in modified atmosphere-packaged fish, will support safe exploitation of these packaging systems in the market place, and identify critical control points for potential product or process abuses. PMID- 2204406 TI - Pharmacokinetics and metabolism of methotrexate: an example for the use of clinical pharmacology in pediatric oncology. PMID- 2204407 TI - Hepatosplenic candidiasis in children with cancer. Three cases in leukemic children and a literature review. AB - Three children with acute leukemia presented with prolonged fever and neutropenia after cytostatic therapy, which was followed by abdominal pain, hepatomegaly, and hepatic dysfunction with raised serum alkaline phosphatase. Abdominal CT scan and ultrasound demonstrated multiple small lesions compatible with the hepatosplenic candidiasis syndrome. Liver biopsies showed microabscesses with a granulomatous appearance, but evidence of yeasts and pseudohyphae was present in 1 case only. Cultures were negative. Treatment with amphotericin B and 5-fluorocytosine was successful in two children. At autopsy, one child had signs of active infection. We reviewed the literature on 27 children with hepatosplenic candidiasis. Abdominal symptomatology and prolonged fever, despite antibiotic therapy, in a patient with previous or present neutropenia after cytotoxic exposure, should lead to a careful evaluation, including noninvasive imaging studies, open liver biopsy, and prompt aggressive antifungal treatment, the response to which requires close follow-up. PMID- 2204408 TI - Heterogeneity of DNA repair: implications for human disease and oncology. AB - DNA repair studies used to be confined to measurements representing an average over the entire mammalian genome. It is now possible to study repair processes at subgenomic levels including specific genes. We will describe such results and discuss the impact they may have on our understanding of important oncological processes. Also, we will describe and discuss some clinical conditions that may have some effect in DNA damage processing. PMID- 2204409 TI - Methotrexate-induced leukoencephalopathy is treatable with high-dose folinic acid: a case report and analysis of the literature. AB - An episode of leukoencephalopathy is reported in a 13-year-old girl who, after standard radiotherapy for a posterior fossa medulloblastoma, received 8 treatments with a protocol containing a 4-hour infusion of 500 mg/m2 methotrexate and 12 mg intrathecal methotrexate. The leukoencephalopathy, documented clinically and by CT and EEG, cleared after 2350 mg of leucovorin (citrovorum factor, folinic acid) was given in addition to the 135 mg given as part of the therapy. A review of the literature suggests that leukoencephalopathy may be prevented by high doses of leucovorin and can be treated by high doses, if lower doses were used initially. When high dose leucovorin was not used, residual neurological damage is not unusual. PMID- 2204410 TI - An approach to protein restriction in children with renal insufficiency. AB - Children with mild to moderate renal insufficiency may be at an increased risk for developing glomerulosclerosis and subsequent renal failure. Low protein diets (LPD) have been shown to delay the progression of renal insufficiency in laboratory animals and may be of benefit in adult humans. The nutritional costs of a LPD in adults are reportedly minimal. We review the protein and caloric requirements of growing children and discuss the potential harmful effects and benefits of an LPD in this population. We also discuss dietary adherence and the difficulty of designing an LPD for children. We conclude that the protein content of a typical American diet can safely be reduced to, but not below, the recommended daily allowance for protein if diets are carefully planned, patients and their parents extensively counseled, and if dietary supplements are given to help meet the caloric and vitamin-mineral nutrient needs of growing children. In addition, ongoing nutritional assessment, counseling, and frequent monitoring of growth, diet and biochemical indicators of protein status are essential for maintaining the health of these children. PMID- 2204411 TI - Day wetting. AB - About 1% of healthy children over the age of 5 years have troublesome daytime wetting. Two-thirds of those who wet by day are reliably dry at night. The problem is more common in girls and is usually the result of urge incontinence. Although the wetting may be exacerbated by giggling and/or stress, pure giggle micturition and isolated stress incontinence are both rare. There is a strong association with bacteriuria (50% prevalence) in girls who wet by day. A potentially important relationship exists between day wetting, infection, reflux and upper tract damage, which is expressed in an extreme form in the syndromes of incoordinated voiding and progressive renal damage. Most children who wet by day have unstable bladders. Many of them adopt characteristic "holding" postures. There is an increased incidence of emotional disorder compared with children who merely wet the bed. Between 10% and 15% of children who wet by day become dry during the next 12 months. The acquisition of dryness is accelerated by eradication of bacteriuria and a sympathetic and energetic management regime, which should place responsibility on the child and result in the child voiding more frequently and completely. Reminder alarms and other behaviour therapies have proved effective. There is no satisfactory evidence for the efficacy of drugs. More complex behavioural training regimes including biofeedback are valuable for severe cases. PMID- 2204413 TI - Membranous nephropathy in childhood and its treatment. AB - Membranous nephropathy is predominantly a disease of middle-aged and elderly individuals, and is thus rather an uncommon finding in proteinuric and nephrotic children. In children, it differs in several important respects from the disease as seen in adults: an apparent associated cause is more common, macroscopic haematuria is seen quite frequently, a relapsing course is more often noted, renal venous thrombosis is not found and evolution into renal failure is the exception. Nevertheless, a proportion of children with membranous nephropathy do evolve into renal failure, and their management is discussed with particular reference to recent papers on the treatment of membranous nephropathy in adults. An aggressive search for associated disease is worthwhile in children, and one should wait to see what the evolution or proteinuria and renal function may be. If a progressive course becomes evident, then a trial of treatment with corticosteroids is worthwhile, but if this is ineffective then a more aggressive approach involving the use of alkylating agents may be justified. It remains undetermined what the best regime in children and adolescents may be. PMID- 2204414 TI - Clinical quiz. Elevated urinary uric acid excretion (UUAE). PMID- 2204415 TI - Importance of minor-groove contacts for recognition of DNA by the binding domain of Hin recombinase. AB - Incorporation of the DNA-cleaving moiety EDTA.Fe at discrete amino acid residues along a DNA-binding protein allows the positions of these residues relative to DNA bases, and hence the organization of the folded protein, to be mapped by high resolution gel electrophoresis. A 52-residue protein, based on the sequence specific DNA-binding domain of Hin recombinase (139-190), with EDTA at the NH2 terminus cleaves DNA at Hin recombination sites. The cleavage data for EDTA Hin(139-190) reveal that the NH2 terminus of Hin(139-190) is bound in the minor groove of DNA near the symmetry axis of Hin-binding sites [Sluka, J. P., Horvath, S. J., Bruist, M. F., Simon, M. I., & Dervan, P. B. (1987) Science 238, 1129]. Six proteins, varying in length from 49 to 60 residues and corresponding to the DNA-binding domain of Hin recombinase, were synthesized by solid-phase methods: Hin(142-190), Hin(141-190), Hin(140-190), Hin(139-190), Hin(135-190), and Hin(131 190) were prepared with and without EDTA at the NH2 termini in order to test the relative importance of the residues Gly139-Arg140-Pro141-Arg142, located near the minor groove, for sequence-specific recognition at five imperfectly conserved 12 base-pair binding sites. Footprinting and affinity cleaving reveal that deletion of Gly139 results in a protein with affinity and specificity similar to those of Hin(139-190) but that deletion of Gly139-Arg140 affords a protein with altered affinities and sequence specificities for the five binding sites. It appears that Arg140 in the DNA-binding domain of Hin is important for recognition of the 5' AAA-3' sequence in the minor groove of DNA. Our results indicate modular DNA and protein interactions with two adjacent DNA sites (major and minor grooves, respectively) bound on the same face of the helix by two separate parts of the protein. PMID- 2204412 TI - Autoimmunity and the pathogenesis of glomerulonephritis. AB - Self-tolerance is maintained by: thymic influences on developing T cells; peripheral mechanisms that can tolerise post-thymic T cells; and to a variable extent the tolerisation of potentially autoreactive B cells. The presence of autoreactive T cells in normal individuals suggests that mechanisms to control the activity of such cells may be important. Failure of any of these processes may lead to autoimmunity. The relationship between glomerulonephritis and the mechanisms leading to breakdown of self-tolerance remains elusive. An important observation is that autoimmune diseases are strongly associated with particular products of the major histocompatibility complex (MHC). This association may reflect the intimate involvement of the MHC in thymic T cell education. Another explanation is that T cells only recognise antigens presented in the context of MHC molecules. Although there has been progress in identifying the targets recognised by autoantibodies in vasculitis and anti-GBM disease, nothing is known about the T cells involved. Despite our ignorance, therapy aimed specifically at the T cell can be effective. This approach is being supplemented by attempts to engage immunoregulatory mechanisms, such as idiotype-antiidiotype interactions. The hope is that such treatments, or combinations thereof, will allow a more focused suppression of the autoimmune response, in contrast to the non-specific (and therefore potentially dangerous) methods of immunosuppression available at present. PMID- 2204416 TI - Orientation of the putative recognition helix in the DNA-binding domain of Hin recombinase complexed with the hix site. AB - On the basis of sequence similarity with other known DNA-binding proteins, the DNA-binding domain of Hin recombinase, residues 139-190, is thought to bind DNA by a helix-turn-helix motif. Two models can be considered that differ in the orientation of the recognition helix in the major groove of DNA. One is based on the orientation of the recognition helix found in the 434 repressor (1-69) and lambda repressor-DNA cocrystals, and the other is based on the NMR studies of lac repressor headpiece. Cleavage by EDTA.Fe attached to a lysine side chain (Ser183- --Lys183) near the COOH terminus of Hin(139-184) reveals that the putative recognition helix is oriented toward the center of the inverted repeats in a manner similar to that seen in the 434 and lambda repressor-DNA cocrystals. PMID- 2204417 TI - Structure of yeast triosephosphate isomerase at 1.9-A resolution. AB - The structure of yeast triosephosphate isomerase (TIM) has been solved at 3.0-A resolution and refined at 1.9-A resolution to an R factor of 21.0%. The final model consists of all non-hydrogen atoms in the polypeptide chain and 119 water molecules, a number of which are found in the interior of the protein. The structure of the active site clearly indicates that the carboxylate of the catalytic base, Glu 165, is involved in a hydrogen-bonding interaction with the hydroxyl of Ser 96. In addition, the interactions of the other active site residues, Lys 12 and His 95, are also discussed. For the first time in any TIM structure, the "flexible loop" has well-defined density; the conformation of the loop in this structure is stabilized by a crystal contact. Analysis of the subunit interface of this dimeric enzyme hints at the source of the specificity of one subunit for another and allows us to estimate an association constant of 10(14)-10(16) M-1 for the two monomers. The analysis also suggests that the interface may be a particularly good target for drug design. The conserved positions (20%) among sequences from 13 sources ranging on the evolutionary scale from Escherichia coli to humans reveal the intense pressure to maintain the active site structure. PMID- 2204418 TI - Crystallographic analysis of the complex between triosephosphate isomerase and 2 phosphoglycolate at 2.5-A resolution: implications for catalysis. AB - The binding of the transition-state analogue 2-phosphoglycolate to triosephosphate isomerase from yeast has been investigated crystallographically. An atomic model of the enzyme-inhibitor complex has been refined against data to 2.5-A resolution to a final R factor of 0.18. The interactions between the inhibitor and enzyme have been analyzed. The inhibitor forms hydrogen bonds to the side chains of His 95 and Glu 165. The latter hydrogen bond confirms that Glu 165 is protonated upon PGA binding. The structure of the complexed enzyme has been compared to that of the unbound form of the enzyme, and conformational changes have been observed: the side chain of Glu 165 moves over 2 A and a 10 residue flexible loop moves over 7 A to close over the active site. Spectroscopic results of phosphoglycolic acid binding to triosephosphate isomerase that have been amassed over the years are also explained in structural terms. The implications for catalysis are noted. PMID- 2204419 TI - Active-site mapping and site-specific mutagenesis of glycinamide ribonucleotide transformylase from Escherichia coli. AB - The affinity reagent N10-(bromoacetyl)-5,8-dideazafolate has previously been shown to inactivate glycinamide ribonucleotide transformylase (EC 2.1.2.2) from Escherichia coli in an active-site-directed manner with a 1:1 stoichiometry [Inglese et al. (1990) Biochemistry 29, 1436-1443]. After a series of mild proteolytic digestions, the dideazafolate label was localized to an active-site peptide attached by an ester linkage to the highly conserved residue Asp 144. Subsequent site-specific mutagenesis of Asp 144 to Asn 144 resulted in a catalytically inactive enzyme that retained the ability to bind substrates and inhibitors. The Asn 144 mutant could be further labeled with the affinity reagent in an active-site-directed stoichiometric fashion; however, the site of modification in this case was His 119. These results imply that Asp 144 may function as a general base within the catalytic center of the transformylase and is in close proximity to His 119 in the folded protein. PMID- 2204420 TI - Structural characteristics of alpha-helical peptide molecules containing Aib residues. PMID- 2204421 TI - The carboxy terminus of the alpha subunit of tubulin regulates its interaction with colchicine. AB - Controlled proteolysis of goat brain tubulin by subtilisin was carried out to investigate regulatory aspects of the binding of colchicine to tubulin. Tubulin S, obtained by the cleavage of the carboxyl termini of both the alpha- and beta subunits of tubulin by subtilisin, exhibited the following differences compared to native tubulin: (a) Reaction with colchicine, which has an optimum pH of 6.8, becomes independent of pH (in the range 5.7-8.0). (b) The colchicine-binding site, which is labile at 37 degrees C (t1/2 = 4-5 h), becomes highly stable (t1/2 greater than 12 h). (c) The affinity for colchicine is lowered. (d) This lowering of affinity arises from a faster dissociation (higher off rate) of the complex. The above characteristics of tubulin S were not shown by a partially digested hybrid in which the C-terminus of the beta-subunit alone was cleaved. The hybrid behaved very much like the undigested native protein. These results strongly suggest that the regulatory switch for colchicine-tubulin interaction is located in a small region (about 15 residues) of the C-terminus of the alpha-subunit of tubulin. Possibilities of the C-termini being involved in nonbonded contacts with the main body of tubulin are also noticed from the change in conformation between tubulin and tubulin S. PMID- 2204422 TI - Spectral perturbations and oligomer/monomer formation in 124-kilodalton Avena phytochrome. AB - We have studied the effects of pH, ionic strength, and hydrophobic fluorescence probes, 8-anilinonaphthalene-1-sulfonate (ANS) and bis-ANS, on the structure of intact (124-kDa) Avena phytochrome. The Pfr form of phytochrome forms oligomers in solution to a greater extent than the Pr form. Hydrophobic forces play a major role in the oligomerization of phytochrome, as suggested by fluorescence and monomerization by bis-ANS. However, electrostatic charges also take part in the phytochrome oligomerization. The partial proteolytic digestion patterns for the Pr and Pfr species are different, but binding of bis-ANS to the phytochrome abolishes this difference and yields an identical proteolytic peptide mapping for both spectral forms of phytochrome. This appears to result from bis-ANS binding at the carboxy-terminal domain, which induces monomerization of phytochrome oligomers. A second bis-ANS binding at an amino-terminal site blocks cleavage sites of trypsin and alpha-chymotrypsin. Bis-ANS especially blocks access of the proteases to the amino-terminal cleavage site that produces an early proteolytic product (114/118 kDa) on SDS gels. The bis-ANS binding does not, however, affect the proteolytic cleavage site that occurs in the hinge region between the two structural domains of phytochrome, the chromophore domain and the C-terminal non chromophore domain. A chromophore binding site in the Pfr form is apparently exposed for preferential binding of bis-ANS, causing cyclization of the chromophore and bleaching of its absorbance at 730 nm. These observations have been discussed in terms of a photoreversible topographic change of the chromophore/apoprotein during the phototransformation of phytochrome. PMID- 2204423 TI - Azotobacter vinelandii flavodoxin: purification and properties of the recombinant, dephospho form expressed in Escherichia coli. AB - The nifF gene coding for the flavodoxin from the nitrogen-fixing bacterium Azotobacter vinelandii (strain OP) was cloned into the plasmid vector pUC7 [Bennett, L. T., Jacobsen, M. R., & Dean, D. R. (1988) J. Biol. Chem. 263 1364 1369] and the resulting plasmid transformed and expressed in Escherichia coli strain DH5. Recombinant Azotobacter flavodoxin is expressed at levels 5-6-fold higher in E. coli than in comparable yields of Azotobacter cultures grown under nitrogen-fixing conditions. Even higher levels were observed with flavodoxin expressed in E. coli under control of a tac promoter. Electron spin resonance spectroscopy on whole cells and in cell-free extracts showed the flavodoxin to be largely in the semiquinone form. The flavodoxin purified from E. coli exhibited the same molecular weight, isoelectric point, flavin mononucleotide (FMN) content, N-terminal sequence, and carboxyl-terminal amino acids as for the wild type Azotobacter protein. The recombinant flavodoxin differed from native flavodoxin in that it exhibited an increased antigenicity to flavodoxin antibody and did not contain a covalently bound phosphate. Small differences are also observed in circular dichroism spectral properties in the visible and ultraviolet spectral regions. The recombinant, dephospho flavodoxin exhibits an oxidized/semiquinone potential (pH 8.0) of -224 mV and a semiquinone/hydroquinone couple (pH 8.0) of -458 mV. This latter couple is 50-60 mV higher than that exhibited by the native flavodoxin. Resolution of recombinant dephospho flavodoxin resulted in an apoflavodoxin that was much less stable than that prepared from the native protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2204424 TI - Study of strong to ultratight protein interactions using differential scanning calorimetry. AB - Data from differential scanning calorimetry (DSC) may be used to estimate very large binding constants that cannot be conveniently measured by more conventional equilibrium techniques. Thermodynamic models have been formulated to describe interacting systems that involve either one thermal transition (protein-ligand) or two thermal transitions (protein-protein) and either 1:1 or higher binding stoichiometry. Methods are described for obtaining binding constants and heats of binding by two different methods: calculation or simulation fitting of data. Extensive DSC data on 2'CMP binding to RNase are presented and analyzed by the two methods. It is found that the methods agree when binding sites are completely saturated, but substantial errors arise in the calculation method when site saturation is incomplete and the transition of liganded molecules overlaps that of unliganded molecules. This arises primarily from an inability to determine TM (i.e., the temperature where concentrations of folded and unfolded protein are equal) under weak-binding conditions. Results from simulation show that the binding constants and heats of binding from the DSC method agree quantitatively with corresponding estimates obtained from equilibrium methods when extrapolated to the same temperature. It was also found from the DSC data that the binding constant decreases with increasing concentration of ligand, which might arise from nonideality effects associated with dimerization of 2'CMP. Simulations show that the DSC method is capable of estimating binding constants for ultratight interactions up to perhaps 10(40) M-1 or higher, while most equilibrium methods fail well below 10(10) M-1. DSC data from the literature on a number of interacting systems (trypsin-soybean trypsin inhibitor, trypsin-ovomucoid, trypsin-pancreatic trypsin inhibitor, chymotrypsin-subtilisin inhibitor, subtilisin BPN-subtilisin inhibitor, RNase S protein-RNase S peptide, avidin biotin, ovotransferrin-Fe3+, superoxide dismutase-Zn2+, alkaline phosphatase Zn2+, and assembly of regulatory and catalytic subunits of aspartate transcarbamoylase) were analyzed by simulation fitting or by calculation. Apparent single-site binding constants ranged from ca. 10(5) to 10(20) M-1, while the interaction constant for assembly of aspartate transcarbamoylase was estimated as 10(37) in molarity units. For most of these systems, the DSC interaction constants compared favorably with other literature estimates, for some it did not for reasons unknown, while for still others this represented the first estimate. Simulations show that for proteins having two binding sites for the same ligand within a single cooperative unit, ligand rearrangement will occur spontaneously during a DSC scan as the transition temperature of the unliganded protein is approached.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2204425 TI - Hexose metabolism in pancreatic islets. Participation of Ca2(+)-sensitive 2 ketoglutarate dehydrogenase in the regulation of mitochondrial function. AB - A rise in extracellular D-glucose concentration results in a preferential and Ca2(+)-dependent stimulation of mitochondrial oxidative events in pancreatic islet cells. The possible participation of Ca2(+)-dependent mitochondrial dehydrogenases, especially 2-ketoglutarate dehydrogenase, in such an unusual metabolic situation was explored in intact islets, islet homogenates and isolated islet mitochondria. In intact islets exposed to a high concentration of D glucose, the removal of extracellular Ca2+ impaired D-[6-14C]glucose oxidation whilst failing to affect the cytosolic or mitochondrial ATP/ADP ratios. In islet homogenates, the activity of 2-ketoglutarate dehydrogenase displayed exquisite Ca2(+)-dependency, the presence of Ca2+ causing a 10-fold increase in affinity for 2-ketoglutarate. In intact islet mitochondria, the oxidation of 2-[1 14C]ketoglutarate also increased as a function of extramitochondrial Ca2+ availability. Moreover, prior stimulation of intact islets by D-glucose resulted in an increased capacity of mitochondria to oxidize 2-[1-14C]ketoglutarate. The absence of extracellular Ca2+ during the initial stimulation of intact islets impaired but did not entirely suppress such a memory phenomenon. It is proposed that the mitochondrial accumulation of Ca2+ in nutrient-stimulated islets indeed accounts, in part at least, for the preferential stimulation of mitochondrial oxidative events in this fuel-sensor organ. PMID- 2204427 TI - Electroinsertion of full length recombinant CD4 into red blood cell membrane. AB - Electroinsertion is a novel technique of protein implantation in cell membranes using electrical pulses, of field strength between 1.3 kV/cm and 2.1 kV/cm and up to 1 ms duration. The full length recombinant CD4 receptor could thus be inserted in human and murine red blood cell (RBC) membranes. 100% of the RBC subjected to this procedure were shown to expose different CD4 epitopes after electroinsertion. An average of 5000 epitopes per cell has been detected by immunofluorescence assay using flow cytometry and whole cell ELISA. CD4 electroinserted in red blood cell membranes showed upon reaction with monoclonal antibody significant patching similar to that observed in T4 cells expressing CD4. Furthermore, the fluorescent enhancement coming from accumulation of immune complex phycoerythrin-antiphycoerythrin was similar for both native CD4 on T4 cells or CD4 electroinserted into erythrocyte membrane. Attempts to electroinsert proteins without a membrane spanning sequence have consistently failed, suggesting that adsorption is not responsible for the observed phenomena. PMID- 2204426 TI - Interaction of renin inhibitors with the intestinal uptake system for oligopeptides and beta-lactam antibiotics. AB - The interaction of two renin inhibitors, S 86,2033 and S 86,3390, with the uptake system for beta-lactam antibiotics and small peptides in the brush border membrane of enterocytes from rabbit small intestine was investigated using brush border membrane vesicles. Both renin inhibitors inhibited the uptake of the orally active cephalosporin cephalexin into brush border membrane vesicles from rabbit small intestine in a concentration-dependent manner. 1.1 mM of S 86,3390 and 2.5 mM of S 86,2033 led to a half-maximal inhibition of the H(+)-dependent uptake of cephalexin. Both renin inhibitors were stable against peptidases of the brush border membrane. The uptake of cephalexin into brush border membrane vesicles (1 min of incubation) was competitively inhibited by S 86,2033 and S 86,3390 suggesting a direct interaction of these compounds with the intestinal peptide uptake system. The renin inhibitors are transported across the brush border membrane into the intravesicular space as was shown by equilibrium uptake studies dependent upon the medium osmolarity. The uptake of S 86,3390 was stimulated by an inwardly directed H(+)-gradient and occurred with a transient accumulation against a concentration gradient (overshoot phenomenon). The renin inhibitors S 86,2033 and 86,3390 also caused a concentration-dependent inhibition in the extent of photoaffinity labeling of the putative peptide transport protein of apparent Mr 127,000 in the brush border membrane of small intestinal enterocytes. In conclusion, these studies show that renin inhibitors specifically interact with the intestinal uptake system shared by small peptides and beta lactam antibiotics. PMID- 2204428 TI - Transepithelial transport of vinblastine by kidney-derived cell lines. Application of a new kinetic model to estimate in situ Km of the pump. AB - We present a new transport model that may be useful for many kinds of transepithelial transport experiments. The model permits estimation of a pump Km and pump activity solely on the basis of transepithelial tracer fluxes. We apply the model to studies of a multidrug efflux pump, P-glycoprotein, which is normally located in the apical plasma membrane of certain transporting epithelia such as kidney proximal tubule cells. To determine the functional properties of this multidrug transporter in an epithelium, we studied the transepithelial transport of the chemotherapeutic drug, vinblastine, in epithelia formed by the kidney cell lines MDCK, LLC-PK1, and OK. We have previously shown that basal to apical flux of 100 nM vinblastine was about five times higher than apical to basal flux in MDCK epithelia, indicating that there is a net transepithelial transport of vinblastine across MDCK epithelia. Addition of unlabeled vinblastine reduced basal to apical flux of tracer and increased apical to basal flux of tracer in a concentration-dependent manner, a pattern expected if there is a saturable pump that extrudes vinblastine at the apical plasma membrane. The model permits estimation of a pump Km and pump activity solely on the basis of transepithelial tracer fluxes. According to the transport model the apical membrane pump has Michaelis-Menten kinetics with an apparent Km = 1.1 microM. Net basal to apical transport of vinblastine was also observed in LLC-PK1 cells and OK cells which are other kidney-derived cell lines. The order of potency of the transport is LLC-PK1 greater than MDCK greater than OK cells. The organic cation transporter is not involved in this vinblastine transport because vinblastine transport in MDCK cells was not affected by 3 mM tetramethyl- or tetraethylammonium. Inhibitors of vinblastine transport in MDCK cells was not affected by potency, were verapamil greater than vincristine greater than actinomycin D greater than daunomycin. The transport pattern we observed is that predicted to result from the function of the multidrug transporter in the apical plasma membrane. PMID- 2204430 TI - Mechanism of penetration and of action of local anesthetics in Escherichia coli cells. AB - Escherichia coli cells were used to study the mechanism of penetration of local anesthetics and the relationship between permeation and functional properties. We show that both the neutral and the protonated form of dibucaine can be accumulated in the cells. Accumulation of the protonated form occurs in response to a transmembrane electrical potential (negative inside) and results in high trapped concentrations (70 mM). Accumulation can lead to an alkalinization of the internal pH. Low concentrations of dibucaine stimulate the respiration, increase the transmembrane electrical potential and raise the accumulation of solutes. Inhibition of these functions occurs at higher concentrations of the drug. Furthermore, the drug concentration required to inhibit these functions is smaller at alkaline external pH than at acidic external pH, suggesting that the inhibition is mainly due to the neutral form of the anesthetics. Other hydrophobic amines also stimulate and inhibit different membrane functions, their efficiency being correlated to their lipophilicity. PMID- 2204429 TI - Interaction of wasp venom mastoparan with biomembranes. AB - Mastoparan-induced changes in the K+ permeability of rat peritoneal mast cells, human erythrocytes, Staphylococcus aureus and Escherichia coli were examined. Mastoparan did not efficiently increase the K+ permeability of cells except for S. aureus. The release of membrane phospholipids was also observed from S. aureus cells in the concentration range of the permeability enhancement. Mastoparan stimulated histamine release from mast cells, independently of a small efflux of K+. Mastoparan became markedly effective to E. coli cells whose outer membrane structure was chemically disrupted beforehand, showing that the peptide can enhance the permeability of the cytoplasmic membranes of both Gram-positive and negative bacteria. In experiments using liposomes, mastoparan increased the permeability of the liposomes composed of egg phosphatidylethanolamine and egg phosphatidylglycerol, which are the lipid constituents of the cytoplasmic membrane of E. coli cells, while it showed a weak activity to the liposomes composed of egg phosphatidylcholine and cholesterol. The latter result related closely to the fact that this peptide acted weakly on erythrocytes and mast cells in which acidic lipids constitute a minor portion. Mastoparan decreased the phase transition temperature of dipalmitoylphosphatidylglycerol liposomes, but it did not affect that of dipalmitoylphosphatidylcholine liposomes. These results indicate that mastoparan penetrated into membranes mainly containing acidic phospholipids and disrupted the membrane structure to increase the permeability. The action of the wasp venom mastoparan was compared with that of a bee venom melittin. PMID- 2204432 TI - Effect of yohimbine on plasma homovanillic acid in panic disorder patients and normal controls. AB - The effects of oral yohimbine (20 mg) or placebo or both drugs on plasma homovanillic acid (HVA) were evaluated in patients with panic disorder and normal controls. Panic disorder patients had similar HVA values at baseline compared with normal controls, and yohimbine failed to produce appreciable changes in HVA in both groups. These findings are discussed within the context of catecholaminergic theories of panic disorder. PMID- 2204431 TI - Characterization of FadL-specific fatty acid binding in Escherichia coli. AB - The product of the fadL gene (FadL) is a central component of the long-chain fatty acid transport system of Escherichia coli. When fatty acid activation is blocked by a mutation in the structural gene for acyl CoA synthetase (fadD) transport is inhibited allowing a FadL-specific fatty acid binding activity to be measured. This binding activity was 4- to 6-fold greater in the fadL+ fadD strain LS6928 when compared to the delta fadLfadD strain LS6929. With long-chain fatty acids, this binding activity was saturable and it was estimated that there were approx. 35,000 FadL-specific oleic acid binding sites per cell in the fadL+ strain LS6928. The FadL-specific fatty acid binding affinity was highest for oleic acid (18:1) and palmitic acid (16:0) giving apparent KD values of 2.3.10( 7) M and 8.8.10(-7) M, respectively. FadL-specific binding affinity of myristic acid (14:0) was nearly an order of magnitude less and no FadL-specific binding of decanoic acid (10:0) could be measured. Two lines of evidence suggest that FadL fatty acid binding occurs by a hydrophobic interaction: (1) There was a preference for the long-chain substrates oleic acid and palmitic acid; and (2) oleic acid binding activity was not significantly changed over the pH range 5.0 to 8.0. The FadL-specific binding of oleic acid in the fadL+ strain LS6928 could be blocked by preincubation with antisera raised against purified FadL providing a clear correlation between the activity and identity of FadL. The binding activity associated with FadL was measured in vesicles of the outer membrane following passage over the hydrophobic resin Lipidex 1000. The KD of oleic acid binding attributable to FadL in outer membranes vesicles (6.0.10(-7) M) was in close agreement with that determined in whole cells. Overall, these studies demonstrated that FadL binds long-chain fatty acids with a relatively high affinity prior to their transport across the outer membrane. PMID- 2204433 TI - Comparison of growth hormone response after clonidine and insulin hypoglycemia in affective illness. AB - Abnormal growth hormone (GH) responses have been observed after several neuroendocrine challenge tests. In the present study, we examined the relationship between GH response after clonidine and insulin administration within the same subject to see if consistent response patterns were evident. Though there was a significant reduction in the mean GH response after clonidine (p = 0.0002), similar differences were not observed after insulin (p = 0.10). Furthermore, there were no apparent within-subject correlations for GH response between the clonidine and insulin challenge tests. Although the present findings indicate an inherent variability in GH response patterns after different neuroendocrine challenge tests, it appears from prior studies that GH may be more consistently blunted after clonidine in depression when compared to other GH provocative tests. PMID- 2204434 TI - Serotonin receptor sensitivity in major depression. PMID- 2204435 TI - Fibril-associated collagens. AB - Many collagen fibrils have been shown to be heterotypic, i.e. composed of more than one collagen type. Fibrils containing type I collagen as the major constituent do also contain, at least in some tissues, type III and type V collagens. Fibrils containing type II collagen have been shown to also contain type XI collagen. The type I, II, III, V and XI collagen molecules are very similar and are clearly derived from a single ancestral gene. However their processings are not identical. While collagen types I and II have a N-propeptide which is cleaved for their insertion in the fibrils, collagen types V and XI keep a N-terminal extension which must include, based on the cDNA derived structures, a short triple helix and a globular domain. They are thought to contribute to the control of fibril lateral growth and diameter. Other collagens are associated with fibrils without having the long triple uninterrupted triple helix characteristic of collagen types I, II, III, V and XI. Type IX collagen has been shown to be covalently cross-linked to type II collagen and to lay at or near the surface of fibrils, with a triple helical arm projecting in the extrafibrillar space a globular N-terminal domain. Type XII collagen is found in type I collagen containing matrices and contains a triple helical domain homologous to the type IX COL1 domain. This suggests a similar function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2204436 TI - Bone induction by osteogenin and bone morphogenetic proteins. AB - Bone induction is a multistep process that includes chemotaxis and attachment of mesenchymal stem cells, proliferation of progenitor cells and differentiation into cartilage and bone. Endochondral bone formation is the predominant sequence. Bone induction can be operationally divided into the following phases: initiation, promotion and maintenance. The initiation of bone induction is primarily regulated by osteogenin and bone morphogenetic proteins. Recent work has led to the isolation, purification and cloning of osteogenin and other bone morphogenetic proteins. Other growth factors such as platelet derived growth factor (PDGF), transforming growth factor beta (TGF-beta isoforms, insulin like growth factors (IGF 1 and 2), and fibroblast growth factor (FGF) may promote and perhaps maintain the newly induced bone. PMID- 2204438 TI - Biochemical and histological evaluation of the synovial-like tissue around failed (loose) total joint replacement prostheses in human subjects and a canine model. AB - The tissue around loose total joint replacement prostheses displays a synovial like lining comprised of cells that produce IL-1 and PGE2, mediators of inflammation that stimulate bone resorption. Particles of titanium alloy, as well as cobalt-chromium alloy and polyethylene, were found to aggravate the histiocytic response and production of IL-1 and PGE2. Tissue with similar histological and biochemical features was produced in a canine model of the aseptic loose cemented femoral stem. PMID- 2204437 TI - Stem cell delivery vehicle. AB - Bone marrow contains a rare class of stem cells capable of developing into a number of mesenchymal tissues. The delivery of these cells to appropriate skeletal sites will require uniquely compatible biomaterials. Porous calcium phosphate ceramics may provide such a vehicle for the repair of bone. The experimental basis for this proposal is discussed. PMID- 2204439 TI - The possible role of collagen fibrils and collagen-phosphoprotein complexes in the calcification of bone in vitro and in vivo. AB - Samples of decalcified chicken bone containing varying concentrations of phosphoproteins from bone or egg yolk (phosvitin) were used in vitro as heterogenous nucleators for the induction induction of Ca-P apatite crystals from operationally metastable solutions of Ca and P in vitro. The lag time between exposure of the collagen-phosphoprotein complexes to a metastable solution of Ca and P and the time nucleation of crystals occurred decreased as the concentration of Ser(P) and Thr(P) increased. Enzymatic cleavage of the phosphate groups by wheat germ acid phosphatase reversed this effect, indicating that the phosphate groups per se are necessary, but may not be sufficient for the facilitation of the nucleation of Ca-P crystals by collagen complexed to phosphoprotein. PMID- 2204440 TI - Biophysical studies of the modification of DNA by antitumour platinum coordination complexes. AB - Cisplatin (cis-diamminedichloroplatinum(II] is widely used in the treatment of various human tumours. A large body of experimental evidence indicates that the reaction of cisplatin with DNA is responsible for the cytostatic action of this drug. Several platinum-DNA adducts have been identified and their effect on the conformation of DNA has been investigated. Structural studies of platinum-DNA adducts now permit a reasonably good explanation of the biophysical properties of platinated DNA. Antitumouractive platinum compounds induce in DNA, at low levels of binding, local conformational alterations which have the character of non denaturing distortions. It is likely that these changes occur in DNA due to the formation of intrastrand cross-links between two adjacent purine residues. On the other hand, the modification of DNA by antitumour-inactive complexes results in the formation of more severe local denaturation changes. Conformational alterations induced in DNA by antitumour-active platinum compounds may be reparable with greater difficulty than those induced by the inactive complexes. Alternatively, non-denaturation change induced in DNA by antitumour platinum drugs could represent more significant steric hindrance against DNA replication as compared with inactive complexes. PMID- 2204441 TI - DNA bending induced by covalently bound drugs. Gel electrophoresis and chemical probe studies. AB - Modification of nucleotide residues arising from the covalent binding of a drug or as a result of irradiation with ultraviolet light can induce distortion of the DNA double helix. The purpose of this review is to show that, from investigation of the electrophoretic mobility of the modified DNA fragments, one can deduce whether the distortions behave more as the centers of directed bends or as hinge joints. It is also demonstrated that chemical probes are a complementary tool for the analysis of distortions at the nucleotide level. PMID- 2204442 TI - Biophysical chemistry of the daunomycin-DNA interaction. AB - Daunomycin (daunorubicin) is a potent anticancer antibiotic that binds to DNA by the process of intercalation. Fundamental aspects of the physical chemistry of the daunomycin-DNA interaction are reviewed here, including the thermodynamics and kinetics of the binding reaction, and recent work that indicates that daunomycin binds preferentially to certain sites along the DNA lattice. The solution studies reviewed here combine with recent theoretical and crystallographic investigations to make the daunomycin-DNA interaction one of the best-characterized intercalation reactions. The molecular interactions that stabilize the daunomycin-DNA complex, and which contribute to its sequence preference, are discussed. PMID- 2204443 TI - The possible role of electron-transfer complexes in the antitumour action of amsacrine analogues. AB - Amsacrine is a DNA intercalating agent which is active against a number of tumours in mice and is used for the treatment of leukaemia in humans. In its DNA bound form, amsacrine efficiently quenches the fluorescence of ethidium. Fluorescence lifetime studies demonstrate two populations of DNA-bound ethidium. The first, whose fluorescence lifetime is constant at approx. 3 ns and whose proportion increases with increasing amsacrine binding ratio, may comprise molecules bound in close proximity to amsacrine. The second, whose fluorescence lifetime is longer and variable (10-24 ns) and whose proportion decreases with increasing amsacrine binding ratio, may comprise molecules three or more base pairs away from ethidium. Studies with a number of derivatives of 9 anilinoacridine containing different anilino substituents suggest that the observed wide variation in quenching capacity is correlated with the magnitude of the substituent dipole moment in a particular direction. Consideration of the geometry of the DNA-binding complex indicates that the negative pole of a dipole established in the anilino ring is directed towards a positively charged site on the ethidium molecule. Quenching of ethidium fluorescence may therefore occur where an electron-transfer complex has formed between ethidium and amsacrine molecules. To ascertain whether electron-transfer complex formation is biologically important in the amsacrine series, ethidium quenching has been quantitated and compared with activity against a transplantable neoplasm in mice, the Lewis lung carcinoma. Compounds which strongly quench ethidium fluorescence are in general highly active antitumour agents. The results are discussed in terms of a model where amsacrine has both a DNA-binding and a protein-binding domain, the latter possibly interacting by formation of an electron-transfer complex. The most likely protein-binding domain is on the enzyme topoisomerase II, the target for its cytotoxic activity. PMID- 2204444 TI - Structure of the adriamycin-cardiolipin complex. Role in mitochondrial toxicity. AB - Adriamycin and its derivatives are among the most efficient antimitotics used in clinical therapy. A specific cardiotoxicity places a limit on the total dose of adriamycin that may be administered. The mechanism of cardiac toxicity is complex. Data accumulated from in vitro and in vivo studies indicate a possible common cause for the inhibition of numerous enzymes and tissue degradation by a free radical mechanism: the binding of adriamycin to the inner mitochondrial membrane cardiolipin. The structure of the adriamycin-cardiolipin complex has been investigated by using physico-chemical techniques and via conformational analysis. The results open a rational way to design new structures that are less cardiotoxic. PMID- 2204445 TI - Ambazone as a membrane active antitumor drug. AB - Ambazone (1,4-benzoquinone guanylhydrazone thiosemicarbazone) was found to be active against various transplantable tumors in mice as well as rats. When administered orally for 4-9 days, the effective therapeutic dose ranged between 60 and 125 mg/kg. The antineoplastic effect of ambazone appeared to be mediated, at least in part, by the immune system. In order to characterize the drug, biophysical and biophysicochemical studies were carried out using thin-layer chromatography, absorption spectroscopy and polarographic measurements. The distribution of ambazone in an n-octanol/water system indicated low hydrophobicity, thereby excluding the possibility of a preferential contribution from hydrophobic forces to the mode of action of ambazone. Ambazone undergoes three protonation reactions with pK values at 10.69 (equilibrium between the negatively charged and neutral forms), 7.39 (equilibrium between the neutral and singly positively charged form) and 6.22 (equilibrium between the singly and doubly positively charge form). Interaction of the drug with model membrane system was monitored by spectrophotometric and fluorescence measurements. Using the fluorescence label 1-anilino-8-naphthalenesulfonic acid (ANS) as a probe pointed to the interaction of ambazone with the inner area of the phospholipid bilayer matrix of liposomes as being nonspecific. Ambazone induces an overall increase in the cellular cAMP content of leukemia cells and macrophages. So far, membrane interaction has provided a molecular basis for both immunological and antineoplastic activities of the drug. By performing DNA melting experiments, it was shown that neutral or singly positively charged ambazone species stabilize the secondary structure of DNA, while the doubly positively charged form binds more strongly and destabilizes the DNA. After oral administration to rats and mice, ambazone was found to be incompletely absorbed from the gastrointestinal tract, to an extent of about 35-50%. Absorbed ambazone binds only weakly to plasma proteins, whereas its binding to red blood cells is relatively strong. The mutagenic potential of ambazone shown in bacterial systems and human lymphocytes corresponds to its relatively weak interaction with DNA. The toxic action of ambazone on the intestine is believed to be due to inhibition by the drug of bacterial DNA, RNA and protein syntheses. It is assumed that the reported affinity of ambazone for different cellular targets, i.e., membranes, nucleic acids and proteins, contributes to the overall antibacterial effect. The weak antiviral activity of ambazone in the Sendai virus/chicken embryo fibroblast system is probably the result of the interaction with Sendai virus NH glycoprotein. PMID- 2204447 TI - French influence on the development of medicine in Louisiana. AB - The paper presents a brief survey of the state of medicine in the 18th century with an emphasis upon developments in France. In the early nineteenth century the emergence of the Paris Clinical School made France pre-eminent in medicine. Its leaders emphasized localism, correlated symptoms with postmortem reports, and introduced clinical statistics. They also introduced the stethoscope and the techniques of auscultation and palpation and were the first to recognize that excessive bloodletting, purging and other depletory measures were harmful. The French population in Louisiana continued to look to France for educational and intellectual leadership well into the nineteenth century, and the findings of the Paris Clinical School had an immediate impact upon Louisiana medicine, leading to a clash between the French-speaking physicians who emphasized moderation and good nursing and the English-speaking practitioners who believed in drastic intervention. PMID- 2204446 TI - Photosensitization by selected anticancer agents. AB - Novel anticancer anthrapyrazoles and anthracenediones are available as alternatives to the cardiotoxic clinical agents, doxorubicin and daunorubicin. Certain representatives of these new classes of compounds possess photosensitizing properties. The structural features influencing the photophysical parameters of these agents are discussed. Photosensitizing reactions involving singlet oxygen production, free radical formation, decomposition of hydrogen peroxide and organic hydroperoxides, oxidation of certain biochemical electron donors, DNA damage and killing of human leukemic cells in vitro in the presence of photoactive anthrapyrazoles, anthracenediones and anthracyclines are described. PMID- 2204449 TI - Mucocutaneous side effects of chemotherapy. AB - Increasing numbers of chemotherapeutic agents are being used to treat patients with cancer. They have only a slight margin of safety between the tumoricidal and toxic doses. The skin is a frequent target for the side effects of these drugs, and the clinician should be alert to these manifestations so that needless diagnostic work up is avoid. PMID- 2204450 TI - Thalidomide in the treatment of graft-versus-host disease. AB - The success of allogeneic bone marrow transplantation has been restricted by the occurrence of graft-versus-host disease (GVHD). Attempts at prevention and treatment of GVHD have resulted in only a limited improvement and the morbidity and mortality rate remains high. Thalidomide has been known to have immunosuppressive properties for over 20 years, but it has only recently been used in GVHD. Evidence is now accumulating as to its value both in animal models, and in humans where most benefit has been seen in chronic GVHD. We report our experience using thalidomide in GVHD following allogeneic bone marrow transplantation and review the literature. PMID- 2204448 TI - Neutrophil dysfunctions in sickle cell disease. AB - The abnormal susceptibility towards certain infections in SCD patients has a partial explanation in the well described functional defects of the spleen and of the alternative complement pathway; such defects probably account for the etiology of fulminant, often fatal, childhood infections with encapsulated organisms (Streptococcus pneumoniae, Haemophilus influenzae). On the other hand, the frequent systemic infections with enteric organisms in SCD patients, particularly of the salmonella species, and also with Staphylococcus aureus, are more difficult to explain. We therefore reviewed the potential contribution of neutrophil (PMN) dysfunctions to the increased infective tendency of SCD patients and included some previously unpublished data from our laboratory. While notable discrepancies still exist--and need further clarification--a tentative working hypothesis can be extracted from the available data: dysfunctions of neutrophils affect their locomotion (as reflected by decreased chemotaxis and in vivo migration), their phagocytic processes and their bactericidal performance. The latter concerns the ineffective killing of Staphylococcus aureus, Candida albicans, and Streptococcus pneumoniae. Dysfunctional bactericidal activity, in turn, apparently relates to a poor or at times non-existent PMN oxidative activity, which prevents the prompt disposal of microorganisms. Under certain circumstances salmonella species seem to further paralyze the oxidative machinery of PMNs in SCD. Serum from some patients contains a poorly defined inhibitor, or lacks an enhancing factor, and such serum abnormalities aggravate the existing defects just described. Interestingly recent findings suggest that dysfunctional PMNs may originate from the mandatory demargination of leukocytes secondary to the functional asplenia of SCD; a predominance of non-rosetting (EA-) PMNs among such leukocytes could produce the operational explanation for an exaggerated representation of dysfunctional PMNs in SCD patients with leukocytis. PMID- 2204451 TI - [Proteolytic degradation of nuclear matrix proteins in the rat liver, Zajdela's hepatoma and hepatoma 22A in the presence of ATP]. AB - An intense proteolytic degradation of both proteins and phosphoproteins has been observed in isolated nuclear matrices from rat liver, Zajdela Hepatoma and Hepatoma 22a, incubated with NP-40, DTT and gamma-[32P] ATP being most intense in Hepatoma 22a. Practically all phosphoproteins of Hepatoma 22a nuclear matrix degraded. This implies either an extremely high proteolytic activity in the preparation or the presence of a specific to phosphoproteins protease absent from rat liver and Zajdela Hepatoma nuclear matrices. PMID- 2204452 TI - [Hormonal regulation of the production of serum albumin by cultured hepatocytes of rats during prenatal and postnatal period of development]. AB - The effects of several hormones on the production of immunoreactive serum albumin (SA) were examined in primary cultures of liver cells obtained from rat fetuses on 21-22 days of gestation of from 3-week old rats. Cortisol, bovine insulin and human growth hormone stimulated SA production in both types of liver cell cultures during 20 h-incubation. L-Triiodothyronine (T3; 10(-9)-10(-7) M) weakly stimulated SA production by hepatocytes from the rats, but markedly inhibited it in cultures of fetal rat liver cells in a dose-dependent manner. In contrast, T3 action on total RNA and protein biosynthesis, estimated as the incorporation of labelled precursors into macromolecules, was stimulatory one in both types of cell cultures. It is concluded that hormonal regulation of SA production is similar in cultured liver cells from fetal and early postnatal rats except for the action of T3. The physiological importance of striking developmental change of T3 action on SA production remains to be determined. PMID- 2204453 TI - [Microcirculatory bed of the epithelial layer of human esophageal mucous membrane in postnatal ontogenesis]. AB - The analysis of histological changes in epithelium layer of mucous membrane and its microcirculatory channel of human oesophagus show that development and formation of epithelium and its capillary channel are interwoven processes. Dynamics of their morphological changes strictly correspond to a definite age stage of organ individual development. Changing each other determined four types of capillaries of mucous membrane epithelium layer and determined the degree of its functional development. PMID- 2204454 TI - Alcohol and mortality: a review of prospective studies. AB - Non-drinkers and heavy drinkers tend to have higher total and cardiovascular mortality rates than light or moderate drinkers. The finding is not disputed; it is the interpretation of this U-shaped curve that is controversial, and in particular the belief that light and moderate drinking protects against coronary heart disease. The British Regional Heart Study of middle-aged British men has shown that 70% of non-drinkers are ex-drinkers. Those ex-drinkers have high rates of doctor-diagnosed illnesses including heart disease, hypertension, diabetes and bronchitis as well as high prevalence rates of measured hypertension, obesity, current smoking and regular medical treatment. Over a five-year period men who were diagnosed as having heart disease, had multiple diagnoses or were put on regular medication had an increased likelihood of becoming non-drinkers or occasional drinkers. The study suggests a downward drift from heavy and moderate drinking towards non-drinking under the influence of accumulating ill health. The data strongly suggest that the observed alcohol-mortality relationships in prospective studies are produced by symptoms and disease present at the time of screening, and by the prior movement of men with such disorders into non-drinking or occasional drinking categories. The concept of a protective effect on mortality which ignores the dynamic relationship between ill health and drinking behaviour is likely to be ill-founded. A review of the major prospective studies reveals an inadequate exploration of the nature of non-drinkers, who are clearly unsuitable for use as a baseline in studies of the effects of alcohol on health. PMID- 2204455 TI - Management of irritable skin disorders in the elderly. AB - Irritable skin conditions are a source of considerable morbidity in the elderly. In order to deal effectively with the problem it is essential to have a working knowledge of the diagnostic features and treatment of the common skin disorders in this age group. PMID- 2204456 TI - Radiology of ovarian varices. AB - The pelvic pain syndrome is a major cause of morbidity in young multiparous women. Psychotherapeutic, medical and surgical treatments are available and therefore accurate diagnosis is important. This article reviews the imaging methods available for the diagnosis of ovarian varices and pelvic venous congestion. PMID- 2204457 TI - The management of change. AB - 'We trained hard--but it seemed that every time we were beginning to form up into teams we would be reorganised. I was beginning to learn later in life that we tend to meet any new situation by reorganising; and a wonderful method it can be for creating the illusion of progress while producing confusion, inefficiency and demoralisation.' (Petronius Arbiter, 210 BC). Many people would probably say that little seems to have changed over the last 2000 years or more. However, such outcomes are not inevitable and this article shows how a more positive response to change can be achieved. PMID- 2204458 TI - Is anorexia nervosa an obsessive-compulsive disorder? PMID- 2204459 TI - Aetiological heterogeneity of schizophrenia: the problem and the evidence. PMID- 2204460 TI - The first case of battle hysteria? PMID- 2204461 TI - Was Hitler a Christian? PMID- 2204462 TI - Cannabis and psychosis. Is there epidemiological evidence for an association? AB - A review of the evidence shows that there is no convincing support for a separate clinical diagnosis of 'cannabis psychosis'. Cannabis can, however, produce brief acute organic reactions and, in moderate to heavy doses, psychotic episodes in clear consciousness. Ingestion in naive users or increasingly heavy use in habitual users can precipitate a schizophreniform episode. Heavy users may have an increased risk of developing schizophrenia in the subsequent 15 years. Well controlled, longitudinal studies are required to explore these associations further and their possible aetiological significance. PMID- 2204463 TI - Combining pharmacological antagonists and behavioural psychotherapy in treating addictions. Why it is effective but unpopular. AB - Supervised administration of disulfiram is one of the very few treatments that can significantly reduce alcohol consumption, yet it is rarely used, despite being simple and cheap. Disulfiram is not 'aversion therapy', but a technique for facilitating exposure and response prevention, and it fits comfortably into a behavioural, social-learning model of addiction (or dependence) and its treatment. The availability of other effective antagonists, notably to opiates, suggests that an approach that is demonstrably effective in alcohol dependence may be helpful in treating other addictions. The reasons for the unpopularity of this approach appear to be largely ideological. PMID- 2204464 TI - Anaesthesia and central nervous system disease in small animals. Part I: General considerations. PMID- 2204465 TI - Anaesthesia and central nervous system disease in small animals. Part II: Anaesthetic management for specific diseases and procedures. PMID- 2204466 TI - Bracken (Pteridium aquilinum): its distribution and animal health implications. PMID- 2204468 TI - Calcitonin gene-related peptide immunoreactivity in neuronal perikarya in dorsal root. AB - Calcitonin gene-related peptide (CGRP) has been localized in neuronal cell bodies in dorsal root ganglia (DRG) and in fibers of the dorsal horn (DH), where it may be involved in transmission of a sensory signal. The capacity of neurons from DRG and dorsal roots (DR) to produce CGRP in culture was examined in this investigation. CGRP-like immunoreactivity was observed in cultured neuronal cell bodies in the DRG and DR. CGRP-positive cell bodies in the DR explains why extirpation of the DRG fails to eliminate CGRP-positive fibers from the DH. PMID- 2204467 TI - Intra-arterial and intramammary injection of miconazole for bovine mastitis caused by Aspergillus fumigatus. PMID- 2204469 TI - Localization of sulfated glucuronyl glycolipids in human dorsal root and sympathetic ganglia. AB - Sulfated glucuronyl glycolipids (SGGLs) in human dorsal root ganglion (DRG) and sympathetic ganglion (SG) were analyzed biochemically and immunohistochemically. SGGLs were enriched in human DRG (1.02 +/- 0.23 micrograms/mg protein), whereas much lower concentrations of these glycolipids (0.043 +/- 0.23 micrograms/mg protein) were detected in SG. Myelin within DRG and SG was immunostained by anti SGGL antiserum, although only a few myelinated fibers were seen in SG. Nerve cell bodies or unmyelinated fibers were not immunostained. Subcellular fractionation study of human DRG demonstrated that these glycolipids were not only enriched in myelin but also in the axolemma-enriched fraction. These data are consistent with the view that SGGLs may be expressed on myelinated fibers in myelin and axolemma, suggesting that these compounds may play an important role in regulating myelinogenesis. PMID- 2204470 TI - The NMDA antagonist, MK-801, suppresses long-term potentiation, kindling, and kindling-induced potentiation in the perforant path of the unanesthetized rat. AB - Antagonism of NMDA-mediated transmission by MK-801 has been shown to block long term potentiation (LTP) in vitro and delay electrical kindling of the amygdala. The present experiment sought to examine the relationship between synaptic potentiation of the perforant path-granule cell synapse and development of perforant path kindling. MK-801 (0.1 and 1.0 mg/kg) blocked induction of LTP of the perforant path in the unanesthetized animal measured 24 h after train delivery. The 1.0 mg/kg dosage also increased afterdischarge (AD) thresholds, delayed kindling development from daily stimulation of the perforant path (means = 8.82 +/- 1.19 and 22.9 +/- 3.66 sessions to the first stage 5 seizure), and increased AD durations. Kindling produced a significant potentiation of the EPSP (47%) and population spike (49%) after the first evoked AD in control animals. No significant enhancement of either component of the field potential was observed in MK-801-treated animals. Animals treated with this dosage of MK-801, did, however, kindle in the absence of potentiation at this synapse. It was concluded that although NMDA-mediated potentiation may facilitate kindling, synaptic potentiation does not appear to be a critical requirement for kindling to develop. These findings support the notion that development of the burst response and not synaptic enhancement may be the critical physiological alteration that underlies the kindling phenomenon. PMID- 2204472 TI - [Changes in body zinc and copper levels in severely burned patients and the effects of oral administration of ZnSO4 by a double-blind method]. AB - The trace elements and the effect of zinc sulphate on wound healing of 46 severely burned patients in recent 2 years were studied. By double blind method 22 patients accepted capsular ZnSO4 (660 mg) per day as treated group and 24 patients medical starch as control. ZnSO4 and placebo were taken from 3rd or 5th day post burn until healing. Serum and 24h urine Zn and Cu were measured on days 3, 5, 9, 13 post burn and later weekly until healing. The changes of Zn and Cu in serum and urine in all patients were similar to the results reported by others. But the serum Zn on day 9 and urine Zn on days 5, 9, 13 post burn in treated group were significantly higher than that in control group. The basic wound healing time was same in both groups, but the patients in treated group whose coefficient UBS* (Unit of Burned Surface) was more than 180 were cured 8 days earlier than the patients of same severity in control group. At the healing the serum Zn in treated group was significantly higher than that in normal control group, while the serum Zn in control group was as same as in normal control group. The rising to normal of value of Zn/Cu in treated group was significantly earlier than that in control group. But the linear regression equations of serum Zn and Cu, urine Zn and Cu in both groups have no significant difference in the whole course of disease. No side effects of ZnSO4 have been found during the course.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2204471 TI - [Bond strength of etched enamel to direct composite resins, to indirect composite resins and to etched and silanized porcelain]. AB - The adhesion to enamel of composite resin inlays are not documented as much as porcelain inlays and direct composite resins. This study evaluates the adhesion of a light cured composite resin (P-50) used in an indirect technique and secondarily polymerized by heat. No significant differences were found between adhesion of P-50 used with an indirect technique and adhesion of porcelain (Mirage). P-50 used with the direct technique yield adhesion values significantly lower than the indirect techniques. PMID- 2204473 TI - Automated continuing education and patient education. AB - This article discusses the use of a computer network to provide instruction for health care providers and patients and provides examples of screens from the educational modules developed for the project. The continuing nursing education and patient education modules were developed as a portion of the components for KARENET (Kellogg Affiliated Remote Environments Network), linking rural Morton, Texas, and the Health Sciences Center at Lubbock, Texas. Both health care providers and patient participants are benefiting from knowledge provided by the methodology of CAI/CMI provided by the network. PMID- 2204474 TI - Factors influencing the development and use of interactive video in nursing education. A Delphi study. AB - The purpose of this study was to identify factors impeding development and use of interactive video (IAV) in nursing education in order to specify actions that would facilitate its development and use. Nurse educators with experience in development of IAV programs were defined as the experts, and a three-round Delphi study was conducted. Study findings revealed that participants were aware of obstacles to development and were able to suggest some ways to overcome them. Subjects clearly identified content they want in IAV programs, and were especially united on applications for simulations. They agreed on benefits of IAV for students, but were less certain about how it might affect faculty roles, and were undecided about measurable advantages of IAV. Conservative predictions were made about how evolving IAV technology might change the process of nurse education in the future. To promote IAV development and use the author recommends cooperative efforts between nurse educators and developers in the business sector and an educational thrust targeted for specific groups. Moving beyond existing nursing roles and institutional models, the author makes two major suggestions: establishment of a new nursing specialist, the nurse/instructional designer, and the creation of an information center staffed by these new specialists who will design and develop programs, provide education and consultation, maintain a clearinghouse for IAV programs, research, and technology, and take a leadership role in the integration of this powerful instructional delivery system into the entire health field. PMID- 2204475 TI - Interaction of iturin A, a lipopeptide antibiotic, with Saccharomyces cerevisiae cells: influence of the sterol membrane composition. AB - The binding of the membrane-active lipopeptide antibiotic iturin A to yeast cells was studied using radioactive iturin A. Saccharomyces cerevisiae had a maximum binding capacity of 5.6 x 10(9) molecules per single cell. The Scatchard plot of binding showed a biphasic profile, with a lower dissociation constant for small concentrations of iturin A. The break of slope at 30 microM iturin A corresponds to the micellization of antibiotic in solution. The binding is also dependent on the nature of the sterol present in the membrane. A mutant yeast strain with a membrane containing cholesterol instead of ergosterol showed the highest affinity for iturin A and the highest sensitivity to this antibiotic, as measured by K+ ion release. In contrast the presence of stigmasterol increased the resistance of the cells to iturin A. PMID- 2204476 TI - Deletion of part of the short arm of chromosome 17 in a congenital fibrosarcoma. AB - Cytogenetic reports of soft tissue sarcomas in children, other than rhabdomyosarcomas, are rare. We report the second cytogenetic analysis of a congenital fibrosarcoma. The tumor had a monoclonal karyotype of 49.XX,+7,+15,+del(17)(p12). PMID- 2204477 TI - Chronic myeloid leukemia with unusual variant Ph translocation (22;22)(q11;q13). Two cases with chimeric BCR-ABL transcripts. AB - We studied two cases of chronic myelogenous leukemia (CML) with unusual variant Philadelphia (Ph) translocation (22;22)(q11;q13). Southern blot analysis showed a chromosomal break in the BCR gene within the 5.8-kilobase (kb) breakpoint cluster region (bcr), between bcr exons 2 and 3 and between bcr exons 3 and 4, respectively. Chimeric bcr-abl mRNA was detected using polymerase chain reaction (PCR) which amplified, according to the respective bcr breakpoints, bcr exon 2 abl exon II and bcr exon 3-abl exon II junction products. These results further support the involvement, even when not cytogenetically detectable, of the 9q34 chromosomal region in all variant Ph translocations and that BCR-ABL gene fusion products are causally involved in the development of Ph positive CML. PMID- 2204479 TI - Prognostic and biological importance of chromosome findings in acute lymphoblastic leukemia. AB - At least 25 structural chromosomal abnormalities are now found in acute lymphoblastic leukemia (ALL). Many of the abnormalities are associated with particular clinical or blast cell features. Chromosomal translocation breakpoints in ALL are among those that define regions of the genome of oncogenic potential, the recognition of which has led to an improved understanding of the mechanisms of leukemogenesis. The prognostic importance of chromosome findings in ALL concerns demonstration of long-term survival in patients with high hyperdiploid leukemic clones and identification of patients with certain translocations who are at high risk of treatment failure and for whom alternative therapy such as bone marrow transplantation may be desirable. This review summarizes the more recent chromosomal findings in childhood and adult ALL and discusses how increasing recognition of structural change and adoption of alternative therapy for high-risk chromosomal groups may change the prognostic role of cytogenetics in this type of leukemia. PMID- 2204478 TI - c-myb gene analysis in T-cell malignancies with del(6q). AB - Three T-cell malignancies with del(6q) were analyzed for karyotypes and alteration of the oncogene c-myb that is assigned to 6q22-q24. Patients were diagnosed as having non-Hodgkin T-cell lymphoblastic lymphoma, adult T-cell leukemia, and acute T-cell lymphoblastic leukemia, and the deletions of chromosome 6 were del(6)(q21q25), del(6)(q21q23), and del(6)(q21) or del(6)(q21q27), respectively. Tumor cell DNAs were obtained from cultured pleural fluid or from fresh peripheral blood and marrow samples and were analyzed by Southern blot hybridization, using c-myb oncogene probes. Rearrangements, deletions, or amplifications were absent in these tumor DNAs, thereby indicating that the del(6q) breakpoint in these T-cell malignancies was located outside of the c-myb gene. Northern blot analysis revealed the elevated expression of c-myb in the non-Hodgkin lymphoma patient, in accord with lineage characteristics. PMID- 2204480 TI - How many signals are enough? AB - The many signals that control the progress of various immune responses to both foreign and self antigens can be divided into no less than three major groups. The first group is the initial positive stimulus, associated with activation events through antigen receptors and their associated proteins. These signals launch lymphocytes in their response to antigen, either foreign or self. The second group of signals is negative and involves various end products and interactions between cells, all recognizing antigen. These signals are endogenous to the reacting cell, or nearly so (two interacting cells from the same clone, daughter cells, which are in the same locale and bind to the same ligand). The third group (the prevention of end product feedback, involving various forms of antigen presentation, T cell contributions, rheumatoid factor activity, and other mechanisms) is more likely to occur with nonself antigens, which are temporally and spatially more restricted than self antigens. Experimental evidence for this immunological schema is summarized and clarified in its relationship to the Bretscher-Cohn theory of self-nonself recognition and to suppressor cell and idiotype-antiidiotypic theories. PMID- 2204481 TI - Analysis of the mechanisms involved in NK resistance induced by a new tumor factor NK-RIF. AB - The mechanisms involved in susceptibility or resistance of neoplasic cells to lysis by NK cells are not well known. We have recently described a 12-kDa factor (NK-RIF), produced and released by different tumor cell lines, making K562 resistant to NK lysis without affecting the cytotoxic function of NK effector cells. In this paper we further study the mechanism involved in NK resistance of K562 mediated by NK-RIF and its biological implications. The results show that NK RIF does not affect the binding capacity of target and effector cells nor the levels of HLA class I antigen expression on the target cells, as a proof that resistance to NK-mediated lysis is not always associated with a defect in target effector binding or with an increased MHC class I antigen expression. However NK RIF-treated K562 loses its capacity to induce NK cell activation and the subsequent capacity to release NKCF and makes K562 resistant to lysis by NKCF. Therefore our results show that induction of resistance to NK cytotoxicity can be the result of the modulation of target structures responsible for inducing effector cell activation without affecting target/effector binding molecules. This indicates that the structures involved in adherence and activation of NK cells have a different nature and that molecules other than HLA participate in NK resistance. PMID- 2204482 TI - Alteration of the immune response to Mycobacterium bovis BCG in mice exposed chronically to low doses of UV radiation. AB - BALB/c mice were exposed on shaved dorsal skin to 1 minimal erythemal dose (MED) of UVB radiation (2.25 kJ/m2) from a bank of six FS-40 sunlamps three times per week. The total number of irradiations ranged from 1 to 27. At regular intervals, groups of mice were injected in the left hind foot pad with 1 x 10(6) live mycobacteria (Mycobacterium bovis BCG) 3 days after the last UVB exposure. The mice were tested 21 and 42 days after infection for a delayed type hypersensitivity (DTH) response to the purified protein derivative (PPD) of tubercle bacilli by injecting PPD into the right hind foot pad and measuring the foot pad swelling 24 hr later. The course of infection was followed by assessing the number of bacterial colony forming units in the lymph node draining the site of BCG infection and the spleen. Mice exposed from 1 to 15 times to 1 MED of UV radiation showed a significant suppression in their DTH response to PPD compared with the unirradiated mice. At the same time, the number of bacterial colony forming units in the lymph node and spleen of the UV-irradiated mice was greater than in control mice. With continued exposure to UVB, however, the DTH response recovered to a normal level, and there was no longer an increase in the number of viable bacteria in the lymphoid organs. These results indicate that early in the course of chronic UV irradiation, mice were impaired in their ability to mount a DTH response to BCG and to clear these bacteria from their lymphoid organs; later the mice recovered from these effects of UV, with continued treatment. A dose response study using single doses of UV radiation indicated that a dose of 2.7 kJ/m2 suppressed the DTH response by 50%. Thus, exposure of mice to a single or multiple low doses of UV radiation prior to infection can interfere with systemic immunity to mycobacteria. PMID- 2204483 TI - Ganglioside reduction of ischemic injury. AB - Systemically administered gangliosides have been shown to be pharmacologically effective in reducing injury and facilitating recovery after CNS damage in various animal paradigms. Very recent work has indicated that ganglioside therapy following CNS ischemia in animals and in humans causes reductions in the extent of injury (acute phase) and enhanced neurological recovery (long-term effects). These studies are reviewed, and the possible mechanisms (i.e., the protection of plasma membrane integrity/function and the modulation of trophic factors) by which gangliosides protect against and reduce brain injury are discussed. PMID- 2204484 TI - Neurochemical, neurophysiological, and neuropathological studies in vitamin E deficiency. AB - It is now recognized that vitamin E is essential for normal neurological structure and function in both man and experimental animals, with severe deficiency resulting in a characteristic neurological syndrome. The reasons why the neurological system should be particularly susceptible to a deficiency of this fat-soluble vitamin, and the mechanisms involved, are not known. In this review, the neurochemistry, neuropathology, and neurophysiology associated with vitamin E deficiency are described and correlated. A deficiency of vitamin E results in a "distal or dying back" axonal neuropathy which predominantly involves the centrally directed fibers of sensory neurons, with the large caliber myelinated fibers being particularly affected. Both the pathological and electrophysiological studies indicate that the primary abnormality is a degeneration of the axons which then results in a secondary demyelination. The mechanism(s) involved is assumed to involve lipid peroxidation of neuronal membranes as a consequence of a deficiency of the major lipid-soluble secondary (i.e., chain breaking) antioxidant in vivo. PMID- 2204485 TI - Neuropathology of AIDS. AB - Involvement of the central and peripheral nervous systems as a result of primary infection by the human immunodeficiency virus (HIV) or due to secondary opportunistic infections and neoplasms has been recognized as a major clinical problem in patients with the Acquired Immunodeficiency Syndrome (AIDS). Currently, of new AIDS cases, 30 to 40% will have clinical evidence of nervous system dysfunction. Neurologic dysfunction will be the presenting problem in 10% of patients. Greater than 75 to 90% of AIDS victims will exhibit nervous system pathology at autopsy. The neuropathologic findings in AIDS can best be examined by separating them into three distinct groups: opportunistic infections, neoplasms, and proposed direct effects of HIV infection. This review considers each of these categories and relates them in turn to the current understanding of the biology of the virus, its epidemiology, and its interaction with the host. PMID- 2204486 TI - The spinothalamic tract. AB - The spinothalamic tract (STT) is made up of axons, originating from neurons in the spinal cord grey matter, which cross segmentally and then ascend to terminate in a variety of thalamic nuclei. The cells of origin of the STT are located throughout the spinal cord in three functional groups. Those located in lamina 1 of the spinal cord have small receptive fields and respond maximally to noxious peripheral stimulation. Those located in spinal cord laminae 4-6 have somewhat larger receptive fields and respond most commonly to both innocuous and noxious stimuli. The group originating in laminae 7-10 have large, frequently bilateral receptive fields and respond to a wide variety of cutaneous and deep stimuli. The largest concentration of STT neurons is found in the upper cervical spinal cord. The terminations of the STT in the thalamus include the lateral sensory thalamus, the intralaminar nuclei (primarily the centrolateral nucleus), and some of the medial nuclei (most prominently the medial dorsal nucleus). The cells located in laminae 1-6 project primarily to the lateral thalamus while the deeper STT neurons project primarily to the intralaminar and medial thalamus. An unique projection of lamina 1 cells to the nucleus submedius has been described. We hypothesize that the deep cells are related to many of the aversive aspects of pain while the more superficial STT cells are related to the sensory discriminative aspects of pain. PMID- 2204487 TI - DNA supercoiling and eukaryotic transcription--cause and effect. PMID- 2204488 TI - [Ectopic pregnancy]. PMID- 2204489 TI - [Diagnosis of hydatidiform changes in the chorion]. PMID- 2204490 TI - [Is tubal sterilization harmful to the health of women?]. PMID- 2204491 TI - [Otakar Kutvirt, his life and fight on behalf of Czech otolaryngology]. PMID- 2204492 TI - [Advances in the diagnosis and chemotherapy of tuberculosis]. PMID- 2204493 TI - [Experimental study and clinical uses of rhubarb]. PMID- 2204494 TI - [Basic research on auricular acupuncture]. PMID- 2204495 TI - Extracellular sodium is required for methacholine-induced secretion of mucus glycoconjugates from canine tracheal explants. AB - Extracellular sodium is known to influence secretion by certain secretory cells, possibly by mobilizing calcium from cellular stores or by altering intracellular pH via regulation of a Na(+)-H+ antiport system. Using canine tracheal explants, we determined whether agents which alter sodium fluxes are capable of modulating basal or cholinergically-induced secretion of mucus glycoconjugates. Methacholine, a cholinergic agonist, increased mucus secretion from explants incubated in the presence or absence of calcium, but had no effect on secretion when incubated in sodium-deficient media, indicating (a) that cholinergically induced secretion can be mediated by mobilization of cellular calcium and (b) that extracellular sodium was required for this stimulatory effect. Several agents which increase intracellular sodium were tested for their effect on mucus secretion. Ouabain, a sodium pump inhibitor, and veratridine, a sodium channel activator, did not significantly affect control or methacholine-induced secretion; gramicidin, a sodium ionophore, also had no effect on basal release. Tetrodotoxin, a sodium channel inhibitor, was also without effect on basal or methacholine-stimulated mucus release. Agents which alter intracellular pH were also examined for their effects on basal or methacholine-induced glycoconjugate secretion. Amiloride, which decreases intracellular pH by inhibiting Na(+)-H+ exchange, produced a 19 per cent increase in basal secretion (not statistically significant), but had no effect on methacholine-induced secretion. An agent, 4,4' diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), which decreases intracellular pH by inhibiting HCO3(-)-Cl- exchange, elicited decreases in both basal and methacholine-induced secretion, but the inhibition did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2204496 TI - Lack of beneficial effects of milrinone in severe septic shock. AB - The effects of milrinone were investigated in a porcine septic shock model. Septic shock was induced by i.v. infusion of live Escherichia coli. Anesthetized pigs were treated with milrinone before the E. coli infusion or were left untreated as septic controls. E. coli caused a significant reduction of cardiac index, renal blood flow, and portal blood flow. Pulmonary vascular resistance was significantly increased, as were the systemic and preportal vascular resistances. One of the seven septic control pigs died. In milrinone-treated septic animals cardiac index was maintained for a longer period of time but blood pressure was significantly reduced compared with the control pigs. Pulmonary vasoconstriction was little affected by pre-treatment with milrinone. Four out of seven milrinone treated pigs died during the observation period. It is concluded that in the settings of the used porcine septic shock model milrinone treatment has no beneficial effect. PMID- 2204497 TI - Dopamine beta-hydroxylase inhibition reveals a selective influence of endotoxin on catecholamine content of rat tissues. AB - Endotoxin is known to affect sympathetic nervous system (SNS) activity. However, it is unknown whether selective activation occurs in different tissues. The present work assessed SNS activity in several tissues of endotoxin-treated rats by measuring the accumulation of dopamine following dopamine beta-hydroxylase inhibition with disulfiram. Twenty-four hours following endotoxin injection (1 mg/kg), body weight and food intake were significantly reduced. The weight of spleen and liver was significantly greater in endotoxin-injected rats compared to either control animals or rats pair-fed the same quantity of food ingested by the endotoxin-treated rats. Norepinephrine (NE) content of heart, liver, and brown adipose tissue (BAT) was significantly lower in endotoxin-injected animals, but it was unchanged in spleen and gastrocnemius muscle. Endotoxin caused a significant elevation in the dopamine content of heart, liver, BAT, and gastrocnemius muscle, whereas it had no effect on spleen. The results suggest that SNS activity is increased in heart, liver, BAT, and gastrocnemius muscle 26 h after endotoxin injection. PMID- 2204498 TI - Cardiac angiotensinogen and its local activation in the isolated perfused beating heart. AB - Increasing evidence suggests that the renin-angiotensin system modulates cardiovascular homeostasis both via its circulating, plasma-borne components and through locally present, tissue-resident systems with site-specific activity. The existence of such a system in the heart has been proposed, based on biochemical studies as well as on the demonstration of renin and angiotensinogen messenger RNA in cardiac tissue. We conducted the present study to determine whether biologically active angiotensin peptides may be cleaved within the heart from locally present angiotensinogen. Isolated, perfused rat hearts were exposed to infusions of purified hog renin; the coronary sinus effluent was collected and subsequently assayed for angiotensin I (Ang I) and angiotensin II (Ang II) by high-pressure liquid chromatography and specific radioimmunoassay. Both Ang I and II were undetectable under control conditions but appeared promptly after the addition of renin. Dose-dependent peak values for Ang I release ranged from 2.42 +/- 0.65 fmol/min to 1.38 +/- 0.18 pmol/min during renin infusions at concentrations between 10 microunits/ml and 5 milliunits/ml. Ang II levels measured in the perfusate reflected a mean fractional intracardiac conversion of Ang I to Ang II of 7.18 +/- 1.09%. Generation of Ang I and Ang II was inhibited in the presence of specific inhibitors of renin and converting enzyme, respectively. To investigate the source of angiotensinogen, we measured spontaneous angiotensinogen release from isolated perfused hearts. In the absence of renin in the perfusate, angiotensinogen was initially released in high, but rapidly declining, concentrations and subsequently at a low, but stable, rate. Prior perfusion with angiotensinogen-rich plasma resulted in enhanced early angiotensinogen release but did not alter the second, delayed phase, suggesting that, in addition to plasma-derived substrate, locally produced angiotensinogen may also participate in the intracardiac formation of angiotensin. Supporting this interpretation, hearts from animals pretreated with dexamethasone showed increased angiotensinogen messenger RNA concentrations as well as increased rates of angiotensinogen release not only during the early but also during the late phase. Our study newly demonstrates that Ang I and II may be formed within the isolated heart from locally present substrate, which appears to be derived in part from the circulating pool and in part from endogenous synthesis. These findings add support to the concept of a functionally active and locally integrated cardiac renin-angiotensin system and emphasize its potential physiological and pathological relevance. PMID- 2204499 TI - Effect of protein kinase C activation on sarcoplasmic reticulum function and apparent myofibrillar Ca2+ sensitivity in intact and skinned muscles from normal and diseased human myocardium. AB - Protein kinase C regulates the activity of a diverse group of cellular proteins including membrane ion channel proteins. Although protein kinase C and its substrate protein have been identified in both membrane and cytosolic fractions in the heart, the physiological role of this kinase in the regulation of cardiac function remains unknown. We examined the physiological role of protein kinase C by stimulating its activity with 12-deoxyphorbol 13 isobutyrate 20 acetate (DPBA) in human trabeculae carneae. This resulted in decreased peak isometric twitch force and peak intracellular sarcoplasmic reticulum calcium release as detected with aequorin. Furthermore, in the presence of DPBA, steady-state force-[Ca2+] relations were shifted to higher intracellular calcium concentrations, and the Hill coefficient was reduced, indicating a decrease in responsiveness of the myofilaments to calcium and a change in cooperativity among thin filament proteins, respectively. Thus, DPBA affects not only intracellular calcium concentration, but myofilament calcium interactions as well. The effect of DPBA on Ca2+ activation probably reflects phosphorylation of thin-filament regulatory proteins by protein kinase C. PMID- 2204500 TI - Detection and estimation of the barley prolamin content of beer and malt to assess their suitability for patients with coeliac disease. AB - Malt, lager, brown ale, bitter and stout were assessed for their barley prolamin (hordein) content. Monoclonal antibody immunoperoxidase staining of electrophoretically separated samples of beer revealed the presence of immunoreactive hordein. Polyclonal antibody based enzyme linked immunosorbant assays (ELISAs) revealed 1.6 mg of hordein per gram of malt and 1.5 mg per pint in the beers. Patients with coeliac disease should avoid ingestion of beer and foods that contain malt since they contain quantifiable amounts of hordein that is known to exacerbate the condition. PMID- 2204501 TI - Determination of alpha 1-antitrypsin in fecal extracts by enzyme immunoassay. AB - An enzyme immunoassay (EIA) has been developed for the determination of alpha 1 antitrypsin (AT). The assay can measure AT in fecal extracts (0.2 g wet feces/ml) from all healthy individuals. Purified human AT was coupled to peroxidase by means of a heterobifunctional reagent and the conjugate was used as a labeled antigen in competitive immunoassays. Concentrations of AT in feces from healthy individuals were less than 0.55 mg/g wet weight or less than 2.2 mg/g dry weight. CV for the physiological day-to-day variance varied between 9 and 140%. After incubation for 48 h at 37 degrees C, the average recovery rates for AT were 78% in ileostomy fluids, 88% in fecal extracts and 92% in feces. Results obtained with EIA correlated well with those obtained with a commercial radial immunodiffusion assay (r = 0.95). PMID- 2204503 TI - Longitudinal study of islet cell antibodies and insulin autoantibodies and development of diabetes in non-obese diabetic (NOD) mice. AB - We have previously shown the presence of circulating islet cell cytoplasmic antibodies (ICA) and insulin autoantibodies (IAA) in the NOD mouse before onset of insulin-dependent diabetes mellitus (IDDM). Here we have determined the levels of the two autoantibodies in 28 female NOD mice longitudinally from approximately day 40 to day 250, to examine their ontogeny, association and predictive value for diabetes. All animals (11 diabetic, 17 non-diabetic) showed varying levels of ICA at some stage, while IAA activity was found in 21 out of 28 mice. Expression of both the markers was seen in more than half of the animals by day 60, with higher levels and rates occurring subsequently in both diabetic and non-diabetic groups. The expression of ICA did not always correlate with that of IAA. There was no apparent difference in the ontogeny of ICA and IAA between the two groups. During the study period the number of animals with ICA was similar in the two groups, while the number of those with IAA was higher in the diabetic animals. In this group declining and rising levels of ICA were seen just before clinical diabetes with frequent peaks of IAA. In the same animals, eight out of 11 mice showed co-expression of high levels of both markers either intermittently or persistently prior to onset, whereas only one non-diabetic animal showed this. We conclude that the ontogeny and serum level of ICA or IAA alone could not be used to predict the clinical onset of diabetes in these animals. However, co expression of high levels of both markers prior to onset may suggest a strong predisposition to clinical diabetes. This may have relevance to attempts to predict the onset of IDDM in humans who have one or both of these immunological markers. PMID- 2204504 TI - Expression of early activation antigen (CD69) during human thymic development. AB - The novel early activation antigen, EA1, has been shown to be induced by mitogens, antigens and the tumour promoter, phorbol myristate acetate (PMA), on human lymphocytes. This antigen has been designated to be CD69. EA1 has also been shown to be expressed on thymocytes without exogenous activation stimuli. In order to characterize further the expression of EA1 on thymocytes, the ontogeny of its expression was studied. EA1 appeared between 7 and 9.5 weeks of gestation, after colonization of the thymic rudiment with CD7+ T cell precursors, but before the onset of compartmentalization of the thymus into cortical and medullary zones. After cortico-medullary differentiation, the majority of medullary thymocytes expressed EA1 while only a fraction of the cortical thymocytes expressed this antigen. In the fetal and post-natal cortex, EA1 expression appeared to cluster in the subcapsular cortex. EA1+ cells were also scattered throughout the inner cortex. By two-colour fluorocytometric analysis of post natal thymocytes, it was shown that EA1 was expressed on 30 to 65% of thymocytes. EA1 was expressed on CD4+ CD8+ as well as on the more immature CD4- CD8- thymocytes. In contrast to circulating T cells, thymocytes were much less responsive to PMA stimulation for the expression of EA1. Molecular characterization showed that EA1 on thymocytes had the same structure as that of activated peripheral T cells. In addition, thymic EA1 was constitutively phosphorylated. Thus, EA1 expression is acquired early during thymic development after colonization of the thymic rudiment by CD7+ T cell precursors. However, the specific role that EA1 may play in the activation and function of developing thymocytes remains to be determined. PMID- 2204502 TI - Selective IgG subclass deficiency: quantification and clinical relevance. AB - Each of the four human IgG subclasses exhibits a unique profile of effector functions relevant to the clearance and elimination of infecting microorganisms. The quantitative response within each IgG subclass varies with the nature of the antigen, its route of entry and, presumably, the form in which it is presented to the immune system. This results in antibody responses to certain antigens being predominantly or exclusively of a single IgG subclass. An inability to produce antibody of the optimally protective isotype can result in a selective immunodeficiency state. This is particularly apparent for responses to certain bacterial carbohydrate antigens that are normally of IgG2 isotype. A failure to produce the appropriate specific antibody response may result in recurrent upper and/or lower respiratory tract infection. Careful patient investigation can identify such deficiencies and suggest appropriate clinical management. In this review we outline the biology and clinical relevance of the IgG subclasses and summarize current rational treatment approaches. PMID- 2204505 TI - Management of the patient with a low HDL-cholesterol. AB - While there is epidemiologic evidence linking a low high-density lipoprotein (HDL) cholesterol level with coronary disease events, and interventions that raise HDL while lowering low-density lipoprotein (LDL) cholesterol levels have been shown to reduce subsequent coronary events, there are no studies showing benefit from raising HDL when a low HDL level is the sole lipid abnormality. HDL is thought to play a key role in reverse cholesterol transport, removing lipids from peripheral cells, but the precise role of HDL in cholesterol metabolism is not understood. The measurement of HDL levels has not been well standardized. Reliance on ratios relating HDL to LDL or to total cholesterol may be misleading in the management of patients. It has not been shown that measuring HDL subfractions or apolipoprotein levels is superior to measuring total HDL levels in predicting coronary risk. HDL levels may be raised by hygienic measures such as smoking cessation and exercise, but a considerable amount of exercise over a long period of time is required. Alcohol consumption and weight loss through dieting inconsistently raise HDL. Estrogen therapy raises and progestational agents lower HDL. Certain beta-blocking drugs lower HDL levels. For the patient with an isolated low HDL level the hygienic measures may be advised, but drug therapy such as nicotinic acid or gem-fibrozil should be prescribed only when low HDL is accompanied by elevated LDL levels that are unresponsive to diet and hygienic measures. PMID- 2204506 TI - Lidocaine in the early phase of acute myocardial infarction: the controversy over prophylactic or selective use. AB - In acute myocardial infarction, lidocaine is considered the drug of choice for the treatment of malignant ventricular arrhythmias. While initially a so-called "selective" treatment strategy prevailed, in which lidocaine was administered only after the onset of certain "warning arrhythmias," the prophylactic use of lidocaine in acute myocardial infarction has been gaining wider usage in intravenous and intramuscular application in recent years. Both therapeutic applications have been found to be problematic of late, which has led to increasingly restrictive use of lidocaine. While in selective treatment forms, the definition and prompt recognition of the so-called warning arrhythmias created especially acute problems, the prophylactic therapeutic use is problematic due to the occurrence of sometimes serious side effects, which is to be expected as the size of the collective being treated increases. Both treatment forms also appear limited by the narrow preventive efficacy of lidocaine against malignant ventricular arrhythmias, especially against ventricular fibrillation. The current therapeutic recommendation for lidocaine in acute myocardial infarction should be limited to patients presenting with very frequent and complex ventricular arrhythmias, especially when these are elicited by an R-on-T phenomenon. Side effects and other therapeutic problems encountered when the therapeutic modality is switched or adjusted can be greatly reduced by careful dosing and selection of the optimal combination substances. PMID- 2204507 TI - Metabolic equivalents (METS) in exercise testing, exercise prescription, and evaluation of functional capacity. AB - One metabolic equivalent (MET) is defined as the amount of oxygen consumed while sitting at rest and is equal to 3.5 ml O2 per kg body weight x min. The MET concept represents a simple, practical, and easily understood procedure for expressing the energy cost of physical activities as a multiple of the resting metabolic rate. The energy cost of an activity can be determined by dividing the relative oxygen cost of the activity (ml O2/kg/min) x by 3.5. This article summarizes and presents energy expenditure values for numerous household and recreational activities in both METS and watts units. Also, the intensity levels (in METS) for selected exercise protocols are compared stage by stage. In spite of its limitations, the MET concept provides a convenient method to describe the functional capacity or exercise tolerance of an individual as determined from progressive exercise testing and to define a repertoire of physical activities in which a person may participate safely, without exceeding a prescribed intensity level. PMID- 2204509 TI - William Townsend Porter. PMID- 2204508 TI - Heart rate variability. AB - Reduced heart rate variability carries an adverse prognosis in patients who have survived an acute myocardial infarction. This article reviews the physiology, technical problems of assessment, and clinical relevance of heart rate variability. The sympathovagal influence and the clinical assessment of heart rate variability are discussed. Methods measuring heart rate variability are classified into four groups, and the advantages and disadvantages of each group are described. Concentration is on risk stratification of postmyocardial infarction patients. The evidence suggests that heart rate variability is the single most important predictor of those patients who are at high risk of sudden death or serious ventricular arrhythmias. PMID- 2204510 TI - Serum aminoterminal type III procollagen peptide in early rheumatoid arthritis: relation to disease activity and progression of joint damage. AB - Serum levels of the aminoterminal type III procollagen peptide (S-PIIINP) have been used as markers of proliferative inflammation in rheumatoid arthritis (RA) and a prognostic significance has been suggested. To test this further we have measured S-PIIINP longitudinally for 2 years in 66 patients with definite RA and a disease duration of less than 2 years, and related the levels to clinical, biochemical, and radiographic findings. In this patient group the correlations between S-PIIINP and ESR and CRP, respectively, were higher than those obtained between S-PIIINP and articular indices, and markedly higher than in patients with RA of longer duration. Patients with normal mean levels of S-PIIINP during the study period had a significantly slower rate of radiographic progression than patients with elevated mean levels of S-PIIINP. ESR yielded in general higher correlations with the joint damage process than did S-PIIINP. The correlations between S-PIIINP and the joint damage scores increased with time. A multiple regression analysis showed that ESR explained most of the variance in joint damage progression over 2 years, but S-PIIINP added independent information. About one third of the variance could be explained by the two variables. PMID- 2204511 TI - Ultrasonography of the metatarsophalangeal and talocrural joints. AB - The unechogenic space between the bone and the joint capsule in 280 metatarsophalangeal (MTP) joints and in 56 talocrural (TC) joints of 28 healthy adults was measured by ultrasonography. These normal values were compared with those of 40 arthritic MTP and of 15 arthritic TC joints. The unecogenic space in the MTP joints was more than 3 mm in 12 out of 280 healthy joints during dorsiflexion. In arthritic joints the space was more than 3 mm in 31 out of 40 joints, and the mean value was significantly higher than in the healthy joints. An unechogenic space could be demonstrated in all the arthritic but none of the healthy TC joints. An unechogenic space of more than 3 mm in a dorsiflexed MTP joint and demonstration of an unechogenic space in a TC joint are signs of intra articular effusion or synovitis. PMID- 2204512 TI - The synthesis and immobilisation of cartilage-specific proteoglycan by human chondrocytes in different concentrations of agarose. AB - Chondrocytes were cultured in agarose gels of different concentrations. In this in vitro model these cells synthesize tissue-specific proteoglycans. The rate of proteoglycan synthesis was not dependent on the concentration of the surrounding gel. The immobilisation of these macromolecules in monomeric and in aggregated form were studied. 0.5% to 1.0% of agarose failed to retain important amounts of proteoglycan. Proteoglycan monomers and even aggregates diffused to the incubation medium. 2.0% and 4.0% of agarose immobilised the bulk of the aggregates and approximately 50% of the monomeric proteoglycans. Low-molecular proteoglycan species or break-down products freely moved out of the gel. The reproducibility of the variables concerning proteoglycan metabolism was very good. PMID- 2204513 TI - Three-dimensional medical imaging modalities: an overview. AB - Three-dimensional medical imaging modalities are reviewed with respect to their underlying science, data-gathering procedure, data interpretation, and image quality. A description of the main components of each data-gathering system is provided, and a brief history of the development of each modality is presented. PMID- 2204514 TI - Evaluation of methodologies for measurement of interstitial fluid pressure (Pi): physiological implications of recent Pi data. AB - As one of the determinants of net transcapillary filtration, filling of initial lymphatics and interstitial compliance, interstitial fluid pressure (Pi) is of great physiological interest. Several methods have been developed to measure Pi, all measuring the fluid equilibration pressure, i.e., the pressure in a saline filled tube brought into contact with the interstitium. The methods designed to establish such contact may be characterized as acute and chronic. With acute methods, i.e., needle without infusion, wick catheters, WIN, and micropipettes, measurements are made within minutes to a few hours after insertion of the device. The chronic methods are various capsules (perforated, porous, or Teflon rings) implanted into the tissue 4 to 6 weeks before measurements. A general finding in previous studies from different laboratories and in different species have been that the chronic methods give more strongly negative (subatmospheric) Pi than the acute methods, and that the chronic methods give much greater pressure responses to changes in IFV. By direct comparison of acute and chronic methods in the same tissue and site, all give similar Pi in steady state conditions, while an acute over- and dehydration results in far more pronounced pressure changes recorded with chronic than with acute devices. It is proposed that these transient pressure differences recorded by acute vs. chronic methods result from different physical properties of the capsule lining compared with that of the surrounding skin, in addition to a possible osmometer effect of the capsule lining. Recent data show that such methodological problems have resulted in great variation in the estimation of compliance of the interstitium and have overemphasized the importance of Pi as an edema-preventing mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2204515 TI - System identification of human joint dynamics. AB - The dynamics of joint mechanics are a fundamental characteristic of the motor system. They determine the displacements evoked by perturbing forces during postural control and the forces that must be generated to perform a voluntary movement. This article reviews experimental studies of these dynamics, with an emphasis on the behavior of single joints in alert humans. Technical aspects of the experimental and analytic methods that have been used are summarized first. Major results obtained with the different methods are then reviewed, compared, and contrasted. The interpretation of these results in terms of the underlying physiological mechanisms is then considered, with an emphasis on the relative contributions of passive properties of tissue, the mechanical behavior of muscle, and stretch reflexes. Finally, important unanswered questions regarding the dynamics of joint mechanics are reviewed. PMID- 2204516 TI - Catheter balloon commissurotomy in adults. Part II: Mitral and other stenoses. PMID- 2204517 TI - The effect of excess suture tension on musculofascial wound healing. PMID- 2204518 TI - Leo Kanner (1894-1981): the man and the scientist. AB - Leo Kanner headed the first child psychiatry division within a pediatric hospital at Johns Hopkins University. In 1935 he wrote the first book in English of child psychiatry which is still in print. His writings include both organic and environmental etiologies. He was an idealist, and he fought for liberal causes and emphasized an humanitarian approach in dealing with autistic children. PMID- 2204519 TI - Intermediate structures in nuclear morphogenesis following metaphase from HeLaS3 cells can be isolated and temporally grouped. AB - Previously nuclear reformation following metaphase in HeLaS3 cells was conceptualized in terms of a stepwise process which was continuous throughout anaphase and telophase. This concept was based on a three-dimensional visualization by scanning electron microscopy (SEM) of individual, organically prepared chromatid structures (prenuclei) which could be sequentially arranged. Morphologic analysis revealed unique topographies and morphometric properties which suggested that it should be possible to isolate populations of prenuclei aqueously. Such an isolation using detergents and density centrifugation is presented which yields metaphase plates and two populations of prenuclei with distinctive morphology. Essentially, prenuclei are freed from late mitotic cells in suspension cultures of synchronized HeLaS3 cells by treatment with 0.1% Nonidet-P40 followed by treatment with a mixture of Tween 40-desoxycholate (0.5%). Critical for the isolation is the presence of a divalent cation (5 mM Mg(+)+) and an acid pH (approximately 5.8). After density centrifugation, 2N decondensing structures (late intermediates) are recovered from 42% Percoll, and a mixture of 2N predecondensing (early intermediates) and 4N metaphase plates are recovered from 52% Percoll. The latter intermediates can be further separated into highly enriched populations (greater than 94% pure) by fluorescence activated sorting. Predecondensing structures are of the same overall morphology as prenuclei isolated previously by organic means, can also be ordered sequentially to demonstrate nuclear morphogenesis, and retain centromere/kinetochore loci. These chromosomal loci based on immunostaining of individual structures appear to be positioned centrally during chromatid reassociation and then appear to be dispersed prior to structural rearrangements leading to formation of a disc-like prenucleus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2204520 TI - [The clinical use of captopril in the diagnosis and treatment of primary aldosteronism]. AB - The responses of blood pressure (BP) and renin-angiotensin-aldosterone system to captopril were studied in 9 patients with primary aldosteronism (PA) including 7 cases of idiopathic hyperaldosteronism (IHA) and 2 cases of aldosterone-producing adrenal adenoma (APA). 2 hrs after the administration of 25 mg captopril, plasma renin activity (PRA) increased significantly, plasma angiotensin II (PAII) and aldosterone concentration (PAC) declined remarkably, BP reduced to normal in 4 of 6 patients in IHA, no changes in PRA, PAII and PAC in patients with APA but significant BP drop in patient with APA. The results suggest sensitivity of the hyperplastic adrenal gland to AII is heightened. It is helpful in the diagnosis of PA, BP can be well controlled with combined captopril (75 mg/d) and small dose of spironolactone (60 mg/d) in most of the IHA. PMID- 2204521 TI - [Free internal mammary artery-coronary artery bypass surgery]. PMID- 2204522 TI - [Endosonographic diagnosis of pancreatic tumors]. AB - 140 patients (72 men, 68 women; mean age 57 [26-83] years) with suspected pancreatic tumours were investigated by endoscopic ultrasound (EUS) and also by conventional ultrasound, computed tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP). The EUS scans were performed with an echo endoscope in the descending part of the duodenum (for the head of the pancreas) or in the stomach (for the body and tail). The definitive diagnosis or exclusion of a pancreatic tumour (malignant n = 85, benign n = 4, inflammatory n = 23, no tumour n = 28) was made at operation (n = 63), by needle biopsy (n = 35), at necropsy (n = 4) or by clinical follow up (n = 38, mean 10.5 months). The sensitivity and specificity of endoscopic ultrasound (99% and 100%) were superior to the results given by conventional ultrasound scans (71% and 39%), CT (82% and 46%) and ERCP (89% and 64%). This was also true of small tumours of 3 cm or less (EUS 100%, conventional ultrasound 57%, CT 68% and ERCP 89%). However, the differential diagnosis between malignant and inflammatory masses in the pancreas was not feasible by endoscopic ultrasound, either prospectively (detection rate 69%) or by comparative analyses of echo structure. Endoscopic ultrasound appears to be a valuable aid to the diagnosis or exclusion of pancreatic tumours. When conventional ultrasound and CT give negative or doubtful results it can be used in conjunction with or instead of ERCP to confirm the diagnosis. PMID- 2204524 TI - [NMR tomography of knee joint injuries]. PMID- 2204523 TI - [Disseminated histoplasmosis as the first manifestation of HIV infection]. AB - A 29-year-old man who had been abroad for several years (mainly Mexico) fell ill with fever (up to 39.8 degrees C), night sweats, weight loss of 10 kg in 6 months (height 181 cm, weight 50.5 kg) and abdominal pain. Computed tomography of the abdomen revealed many enlarged abdominal lymph nodes. Serological tests were positive for HIV antibodies. Fine-needle biopsy of one of the enlarged lymph nodes revealed numerous macrophages with round inclusions, typical for Histoplasma capsulatum. Disseminated histoplasmosis was confirmed by direct antigen demonstration in serum and urine. The patient's serious clinical condition clearly improved and lymph node enlargement regressed after starting specific i.v. treatment with amphotericin B (initially 20 mg/dl, then 50 mg/dl). Although complete cure of the histoplasmosis in connection with the HIV infection is not to be expected, the patient has remained without symptoms for four months on 50 mg weekly of amphotericin B i.v., later changed to imidazole derivatives (400 mg ketoconazole or 200 mg itraconazole, respectively. PMID- 2204525 TI - [Imaging diagnosis of diseases of the pancreas]. PMID- 2204526 TI - Local infiltration of T-lymphocyte subsets as a prognostic indicator in patients with nasopharyngeal carcinoma. AB - We studied tumor-host interactions in 47 patients with NPC. The local infiltration of T-lymphocyte subsets was investigated by an immunoperoxidase technique using monoclonal antibodies. Biopsy specimens of patients without cervical metastasis showed more T-lymphocyte (T11) infiltration. The amount of Leu-3a (helper/inducer) and T8 (cytotoxic/suppressor) cell infiltration did not correlate with the age, sex, clinical stage, and peripheral blood T4 and T8 cells of the patients. A higher incidence of Leu-3a cell infiltration was found in patients with high serum IgA antibody titers to EBV VCA. A trend of better prognosis was revealed in those cases with no or slight stromal T8 cell infiltration. A local immune response was found to exist which may prevent the spread of NPC to the cervical nodes, but this needs further study to evaluate the local infiltration of T-lymphocyte subsets as a prognostic indicator. PMID- 2204527 TI - The intercostal-to-phrenic inhibitory reflex in the human fetus near term. AB - Human fetal breathing movements (FBM) differ from neonatal breathing in that they are predominantly paradoxical and are not present all the time. Respiratory pauses are common in the fetus while prolonged apneas are life-threatening in the neonate. In the latter they occur during state 2 (active sleep) when paradoxical breathing is more frequent. Then the inward movement of the thoracic wall causes spreading of the caudal ribs which may elicit an intercostal-to-phrenic inhibitory reflex (IPIR) leading to apnea. This is not the case in state 1 (quiet sleep). In the fetus similar sleep states, state 2F and 1F respectively, have been identified and we investigated if the IPIR is already present before birth and if so, if the response is different between 1F and 2F. In 21 healthy fetuses between 37 and 40 weeks, two real time scanners and a cardiotocograph were used to asses the fetal behavioural state. If FBM were present, the caudo-lateral part of the fetal thoracic wall was shortly compressed manually and the period that FBM ceased measured. During the same epoch moments of sham-stimulation, i.e. control periods without actual compression were also carried out. In 15 out of 16 fetuses with FBM in 1F, and in 19 out of 19 fetuses in 2F, compressions were immediately followed by an apnea. In contrast, moments of sham-stimulation never induced apnea, indicating that the IPIR is indeed present in both behavioural states.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2204528 TI - Fetal heart rate in early pregnancy. AB - Heart rates were measured by transvaginal sonography twice weekly in ten first trimester fetuses in women who conceived after in-vitro fertilization (IVF) or zygote intra-fallopian transfer (ZIFT). From week 6 to week 9 of menstrual age a rapid increase of the mean heart rate was observed from 113 to 167 beats per min, followed by a slow decrease to 156 beats per min. A close correlation between crown-rump length and heart rate was established. PMID- 2204529 TI - [The molecular mechanisms of hormonally regulated glucose transport]. PMID- 2204530 TI - [The possibilities of influencing the smooth muscle activity of the respiratory tract with calcium antagonists]. PMID- 2204531 TI - Ultrasound, CT and MRI of ruptured and disseminated hydatid cysts. AB - Three cases of echinococcus granulosus with rupture of hydatid cysts and widespread abdominal, pelvic or pleural dissemination are described. Ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) allowed recognition of ruptured hydatid cysts. This assisted to come to an appropriate therapy and exclusion or confirmation of hydatid cysts elsewhere in the body. Ultrasound, CT and MRI are also important for follow-up, evaluation of therapeutic response and/or early diagnosis of recurrence. PMID- 2204532 TI - Computed tomographic changes of the brain in toxaemia of pregnancy. AB - Four cases of toxaemia of pregnancy examined with computed tomography scans of the brain are reported. A review of the literature reveals 19 other cases with previously reported CT brain scans. The review shows intracerebral oedema as the main finding. Haemorrhage, massive or punctate was noted in four cases. The pathogenesis of the CT changes and the clinico-radiological correlation of the visual disturbances are discussed. PMID- 2204533 TI - Detection of renal and renal pelvic tumours with urography and ultrasonography. AB - Urography and ultrasonography of the urinary tract were compared prospectively and blindly in 1306 patients. The patients were a non-selected group referred for urography over 1 year. Renal cell carcinomas were detected in seven patients and carcinomas of the renal pelvis in four patients. Urography detected carcinomas in 10 patients (sensitivity 91%) and falsely suggested malignancy in 52 (specificity 96%). Ultrasonography detected carcinomas in 10 patients (sensitivity 91%) and falsely suggested malignancy in 13 (specificity 99%). No difference between the two methods in detecting renal and renal pelvic tumours was observed in the studied population. PMID- 2204534 TI - Aneurysmal intrahepatic porto-capsular vein anastomosis. AB - Two cases of intrahepatic porto-capsular vein anastomosis are described, both of which were complicated by liver cirrhosis and hepatocellular carcinoma. In both cases a branch of the portal vein in the posterior segment of the liver was markedly dilated and directly anastomosed at its periphery with the liver's capsular vein, then connected with the inferior vena cava. One of the two cases underwent partial hepatectomy. Histopathological examination of the resected specimen did not reveal any direct relation between the shunt and the carcinoma. The shunting in both cases appeared to have resulted from portal hypertension complicated by liver cirrhosis. PMID- 2204536 TI - Proconvulsant effect of SKF 38393 mediated by nigral D1 receptors. AB - This study investigated the hypothesis that the proconvulsant action of systemically applied dopamine D1 receptor stimulants is mediated by D1 receptors in the substantia nigra. Rats were equipped with bilateral stainless steel guide cannulas under halothane anaesthesia, to allow drugs to be injected into both nigras of conscious, unrestrained animals 7-14 days later. Bilateral intranigral administration of saline, together with a subconvulsant dose of pilocarpine (200 mg/kg), produced no convulsions in 14 rats. By contrast, intranigral SKF 38393 (2.5 micrograms) and pilocarpine (200 mg/kg) caused 18/22 rats to convulse. This proconvulsant action of SKF 38393 was completely attenuated by pretreatment with SCH 23390 (0.25 mg/kg). SCH 23390 (1 microgram) delivered into both nigras reduced the number of rats convulsing in response to 600 mg/kg pilocarpine (7/15, one fatally) as compared to saline-injected controls (12/13, eight fatally). These results indicate that dopamine D1 receptors in the substantia nigra (pars reticulata) mediate a proconvulsant action of dopamine, which is opposite to the anticonvulsant effect of the amine at striatal D2 receptors. PMID- 2204535 TI - Gastric lymphoma: diagnosis and follow-up of chemotherapy-induced changes using real-time ultrasonography: a report of three cases. AB - Three cases of secondary gastric lymphoma are presented in which diagnosis was suggested by ultrasound (US) and confirmed by endoscopy and microscopical examination. Three different US patterns are illustrated and compared with endoscopy. US findings paralleled endoscopy during follow-up under antiblastic treatment: both improvement and lack of change in the gastric lesions were reliably predicted by US. PMID- 2204537 TI - Inhibition of neuronally induced relaxation of canine lower esophageal sphincter by opioid peptides. AB - Opioid peptides have profound effects on gut motility. To assess their actions on enteric neurons regulating sphincteric smooth muscle, the ability of several opioid agonists to antagonize the neuronally induced relaxation of canine lower esophageal sphincter smooth muscle was examined. Opioid peptides selective for mu (FK 33-824) or delta [( D-Pen2,D-Pen5]enkephalin) receptors produced a concentration dependent inhibition of electrical field stimulation (EFS)-induced relaxation. In contrast, neither kappa (ketocycloclazine) or sigma (SK & F 10047) opioid agonists were potent inhibitors of EFS-induced relaxation. This inhibition was relatively selective for opioid agonists since BHT 933 (alpha 2 adrenoceptor agonist) and SK & F 89124 (D2 dopamine agonist) did not inhibit EFS-induced relaxation. Furthermore, naloxone antagonized the effects of both FK 33-824 and DPDPE. These functional data suggest that opioid receptors are present on sphincteric intrinsic inhibitory neurons and that stimulation of these neuronal receptors can regulate lower esophageal sphincter relaxation. PMID- 2204539 TI - The biology of hematopoietic growth factors: studies in vitro under serum deprived conditions. PMID- 2204538 TI - Gap-junctional communication of bone marrow stromal cells is resistant to irradiation in vitro. AB - Bone marrow is one of the most radiosensitive organs. Irradiation causes a marked decrease in the total number of hematopoietic cells in the bone marrow. The reticular meshwork structure of marrow stromal cells, however, is relatively resistant to irradiation. Unimpaired stromal cell structure has been thought to be a prerequisite for the repopulation of hematopoietic cells during recovery from the effects of irradiation. The reticular framework is maintained by cell adhesion apparatuses such as gap junctions. The in vitro radiobiologic survival values of a cloned stromal cell line, H-1/A, were studied (n = 1.8, D0 = 138 cGy). Radiation doses of up to 4000 cGy had no detectable effects on the production of colony-stimulating factor 1. H-1/A cells communicate with each other via gap junctions as determined by the sensitive dye-transfer method. Gap junctional communication between H-1/A cells was resistant to different levels of irradiation (500 to 10,000 cGy), but it was lost during adipocyte differentiation of H-1/A cells. Marrow stromal cells, which are important in the recovery of hematopoiesis, seemed capable of coordination with each other through gap junctions even when exposed to radiation. PMID- 2204540 TI - Indomethacin augments granulocyte-macrophage colony-stimulating factor-induced hematopoiesis following 5-FU treatment. AB - We have previously reported that granulocyte-macrophage colony-stimulating factor (GM-CSF) given after the administration of 5-fluorouracil (5-FU) results in augmented hematopoietic recovery as evidenced by increased white blood cell and neutrophil counts. Mice receiving GM-CSF following 5-FU administration were observed to have a marked elevation in splenic granulocyte-macrophage colony forming cells (GM-CFC) and a decrease in the femoral bone marrow GM-CFC. Because GM-CSF has been shown to increase prostaglandin synthesis and prostaglandins are thought to provide a negative feedback signal to down-regulate myelopoiesis, we sought to determine if the cyclooxygenase inhibitor, indomethacin, could prevent the reduction in the number of femoral bone marrow GM-CFC seen when GM-CSF was administered following 5-FU. Groups of mice received a single 60 mg/kg i.p. injection of 5-FU followed 24 h later by twice-daily injections of 1 micrograms GM-CSF and daily injections of 3, 5, or 6 mg/kg indomethacin; the hematopoietic assays were performed on day 7 following 5-FU. Compared to those animals that received GM-CSF alone following 5-FU, mice receiving 5 mg/kg indomethacin plus GM CSF following 5-FU had increased numbers of GM-CFC in their bone marrow (3923 +/- 634 vs 971 +/- 138; p less than 0.001) as well as increased neutrophil counts (18,995 +/- 2872 vs 11,497 +/- 2476; p less than 0.01). Indomethacin alone was, in part, capable of facilitating hematopoietic recovery following 5-FU administration, but not to the extent seen when used in combination with GM-CSF. Prostaglandin inhibitors may have a role in combination with hematopoietic growth factors in accelerating hematopoietic recovery following cytoreductive chemotherapy. PMID- 2204541 TI - 13-cis retinoic acid augments the production of macrophages in mouse bone marrow cultures stimulated with interleukin 3. AB - Mouse bone marrow cells in liquid culture with interleukin 3 generate nonadherent granulocytes, mast cells, and macrophages. The addition of 13-cis retinoic acid (13cRA) (10(-8)-10(-6) M) enhanced proliferation of the nonadherent cells, and concentrations greater than 5 x 10(-7) M stimulated a sixfold increase in adherent macrophages. Four-color flow cytometry was used to identify the lineages present using the following antibodies: MAC1 (granulocytes and macrophages), F4/80 (macrophages), B54.2 (mast cells), and H12 (anti-Thy1.2 to identify myeloid precursors). This analysis demonstrated a twofold increase in MAC1+ F4/80+ cells, which were sorted and identified morphologically as macrophages. 13cRA also increased by 60%-95% the numbers of colony-forming cells responsive to interleukin 3 (IL-3) and macrophage colony-stimulating factor (M-CSF) but did not significantly change the colony-forming cells responsive to granulocyte macrophage colony-stimulating factor (GM-CSF). These data suggest that 13cRA increases the production of macrophages by modulating the commitment of IL-3 expanded progenitor cells to the macrophage lineage. PMID- 2204542 TI - The propriobulbar respiratory neurons in the cat. PMID- 2204544 TI - The laminar distribution and postnatal development of serotonin-immunoreactive axons in the cat primary visual cortex. AB - The laminar distribution and postnatal development of profiles immunoreactive to antibodies directed against serotonin (5-hydroxytryptamine, 5-HT) have been investigated in the primary visual cortex (striate cortex, area 17) of cats. In the adult cat, profiles with serotonin-like immunoreactivity consist exclusively of fibers which exhibit laminar differences in density and predominant orientation. Immunoreactive fibers are dense in layers I-III, less dense in layer V, and sparse in layers IV and VI. In layers I and VI the trajectories of these fibers are mainly tangential to the pial surface; in layers II-V they are predominantly radial and more irregular. The vast majority of immunoreactive fibers consists of fine axons with frequent small varicosities. In addition, there are a few thick axons. In 2-week-old cats, immunoreactive fibers are sparsely distributed through layers II-V. By 4 weeks, fiber density has decreased still further in layer IV and increased in layers I-III. By 6 weeks, the laminar pattern resembles that of adult cats except that fiber density is still lower than in adults. At three months of age, the mature pattern is established. PMID- 2204543 TI - Functional differentiation between the anterior and posterior Clare-Bishop cortex of the cat. AB - A total of 783 cells were studied extracellularly in anterior (A10-13), posterior (A4-8), and intermediate regions (A8.1-9.9) of Clare-Bishop (CB) cortex of the cat, which were defined according to the anteroposterior coordinate of the stereotaxic axis and probably corresponded to the antero- (AMLS), postero-medial lateral suprasylvian cortex (PMLS), and the border region between the two subareas, respectively. The study was conducted under N2O anesthesia supplemented with continuous infusion of short-lasting anesthetics (Saffan, Glaxo or Etomidate, Janssen), using three types of visual stimulators presenting two- (2D) and three-dimensional (3D) motion stimuli, and visual cues contained in the 3D motion. Neuronal responsiveness was essentially similar between the anterior and posterior CB subdivisions. Both areas contained 1) AP, 2) RC and 3) FP cells, selectively responsive to approaching, recessive and fronto-parallel motion, and 4) NS and 5) U cells, nonselectively responsive and unresponsive to any of these motions. However, a quantitative difference was found: 1) In the posterior CB the FP cell population was the largest, and the frequency reduced in the order of AP, NS, RC and U cells, while the largest population in the anterior CB consisted of the AP and U cells, and the frequency reduced in the order of FP, RC and NS cells. 2) 3D (AP and RC) cells in the posterior CB responded preferentially to approaching motion at a distal range, while those in the anterior CB preferred motion at a proximal range. 3) The 3D cells in the posterior CB were more sensitive to the motion cue and demonstrated lower thresholds for the size cue than the anterior CB cells. 4) The anterior CB cells generally demonstrated high pass velocity tuning (cut-off around 10 degrees/s) for monoclonal 2D stimulation, while the posterior CB cells demonstrated a broad band-pass tuning (4-120 degrees/s). These findings suggest functional differentiation in neuronal representation of 3D motion signals between the two subdivisions of CB cortex. PMID- 2204545 TI - Sensory representation of the wing in the spinal dorsal horn of the pigeon. AB - Somatotopic organization and response characteristics were examined in 234 dorsal horn neurons in the cervical enlargement of the spinal cord of anesthetized pigeons. Neurons located in the nucleus proprius (laminae III-V) were activated by light mechanical stimulation (movement of feathers) of cutaneous receptors. Both slowly adapting and rapidly adapting responses were observed, the latter being more numerous. Although most neurons responded to vibratory stimuli, an input from Pacinian-like receptors (Herbst corpuscles in birds) has still to be demonstrated. There was no evidence of an input from high-threshold receptors (nociceptors). Latencies to electrical stimulation of the receptive field suggest a contribution of large myelinated afferent fibers only. Neurons in the avian Clarke's column (within lamina V of the cervical enlargement) were activated by proprioreceptor stimulation. Receptive fields were usually small but larger on proximal parts of the wing (forearm and arm) than on distal parts (hand with fingers). There was a distinct topographic organization of receptive fields. Rostral parts of the wing (prepatagium, alula) were represented rostrally (C12, C13) and caudal parts (secondaries) caudally (C14). Furthermore, distal and ventral parts of the wing were represented medially and proximal and dorsal parts laterally. Despite its very specialized function (bird flight) the somatotopic representation of the wing in the spinal dorsal horn is very similar to that of the forelimb of mammalian species. PMID- 2204547 TI - Assessment of cardiac risk before vascular surgery by dipyridamole thallium testing. PMID- 2204546 TI - Magnetic resonance imaging of the rhesus monkey brain: use for stereotactic neurosurgery. AB - Standard stereotactic procedures rely upon external cranial landmarks and standardized atlases for localization of subcortical neural regions. Magnetic resonance imaging permits the visualization of the neural structure of the brain in vivo. A stereotactic instrument compatible with a magnetic resonance unit was constructed and together with magnetic resonance imaging a procedure was developed that overcomes the limitations and inaccuracies of the traditional stereotactic methods and allows accurate and reliable localization of subcortical targets in the rhesus monkey brain. PMID- 2204548 TI - Long saphenous vein saving surgery for varicose veins. A long-term follow-up. AB - The autologous saphenous vein is widely recognised as the graft material of choice in infra-inguinal arterial reconstructions. This study was undertaken to evaluate the long-term results of long saphenous vein saving surgery compared with standard stripping. Forty-two patients with varicose veins were randomly allocated to treatment, either with standard stripping of the long saphenous vein or high ligation. In both groups, local varicosities were avulsed and insufficient perforators ligated, on the basis of physical examination and phlebography. Follow-up was performed 52 +/- 5 months postoperatively. The recurrence rate was 12 and 11% in the stripping and the high ligation group respectively. At follow-up, the venous return time was increased significantly in both groups (P greater than 0.001). Vein mapping by means of high-resolution, real-time ultrasound at follow-up showed that 78% of the preserved saphenous veins were suitable for use as arterial conduits. These results suggest that removal of the long saphenous vein per se is of no therapeutic value if insufficient perforators have been ligated. It is possible to perform elective vein surgery for varicose veins with good results and preserve the long saphenous vein, which in turn can be used for future arterial reconstruction in most cases. PMID- 2204549 TI - Acute critical ischaemia of the limb: a prospective evaluation. AB - A total of 119 patients with acute peripheral arterial ischaemia were studied prospectively to validate the definition of acute critical ischaemia suggested by the working party of the International Vascular Symposium. The majority of the patients had primary treatment using thrombolytic therapy. Overall limb salvage after 30 days was achieved in 56% of the patients, 19% required amputations and 25% died. Comparisons of the outcome in patients with or without a distal neurosensory deficit (limb salvage 30% vs. 72%, P = 0.0001) and those with absent or audible Doppler ankle blood flow (limb salvage 37% vs. 78%, P = 0.0001) confirmed that the severity of the initial ischaemia was a significant indicator of prognosis. The definition of acute critical ischaemia as assessed by objective measurement of Doppler pressures has been validated and can be used to divide patients into groups with critical and sub-critical ischaemia with different prognoses. PMID- 2204550 TI - Limb loss with patent infra-inguinal bypasses. AB - To determine systemic and local risk factors that contribute to limb loss despite a patent infra-inguinal bypass graft and how to prevent it, we reviewed 987 patients who underwent infra-inguinal bypasses at our institution. Seventy-five (7.6%) patent grafts failed to achieve a healed foot despite exhaustive attempts to do so and these patients underwent major amputation either above the knee (AKA) or below the knee (BKA). In 525 femoro-popliteal bypasses, there were 38 major amputations (29 BKA; 9 AKA) with a patent graft; in 462 femoro-distal bypasses, there were 37 amputations (22 BKA; 15 AKA) with a patent graft. The remaining 912 patients with limb salvage as well as all the patients with limb loss were evaluated with regard to systemic risk factors, quality of the run-off from the popliteal artery, continuity of the tibial artery into the arch as demonstrated on arteriography, the haemodynamic improvement obtained postoperatively, and the presence and extent of necrosis in the foot. The presence of diabetes, extensive pedal necrosis and advanced infection predispose to limb loss despite a patent lower extremity bypass graft. Patients who lost their limbs despite a functioning bypass to an isolated popliteal segment had significantly less pronounced haemodynamic improvement postoperatively. An early graft extension to a reconstituted tibial or peroneal artery or a direct bypass to a distal tibial or peroneal artery may reduce the incidence of limb loss in this setting. When a patent bypass to an isolated tibial or peroneal artery segment failed to relieve foot ischaemia, limb salvage was achieved by a distal extension to plantar arteries. PMID- 2204551 TI - Donor insemination--a look to the future. AB - In this article we have reviewed many aspects of donor insemination. The deficiencies in the screening of semen donors especially for sexually-transmitted diseases has been discussed and importance of a rational protocol for recruitment and screening of potential donors has been emphasized. Factors influencing the success and outcome of donor insemination have been reviewed with particular emphasis on providing prognostic guidelines to potential donor insemination couples as to the success and outcome of the treatment. The importance of accurate timing of inseminations in determining the success of donor insemination has also been discussed. However, as has been highlighted throughout this review, there is a lack of specific prospective controlled trials, which are clearly necessary to answer specific important questions. Also emphasized has been the need of these trials to answer such basic questions as the influence of accurate timing on conception rates in specific groups of insemination recipients. PMID- 2204552 TI - Uterine endometrial peristalsis--a transvaginal ultrasound study. AB - Peristaltic movements of the endometrium were evaluated by serial transvaginal ultrasound throughout 21 spontaneous menstrual cycles, 15 oral contraceptives (OCs) cycles, and 18 in vitro fertilization (IVF) cycles. A score of 0, 1, or 2 was assigned for absent, mild, or strong movements. An average score of 1.5 was obtained at midcycle in spontaneously ovulating women, which was significantly different from early or late follicular (0.36 and 0.5) or luteal (0.4) phase scores. Significant differences were found among the three groups: IVF patients averaged more movements than natural cycle patients, who in turn had a higher incidence than patients taking OCs. Increased peristaltic endometrial movements appear to occur in women around midcycle, probably as an enhancing mechanism for sperm propulsion towards the tubal ostia. PMID- 2204553 TI - Relative efficiency of therapeutic donor insemination using a luteinizing hormone monitor. AB - A prospective randomized study was performed to evaluate the use of a urinary luteinizing hormone (LH) detection kit with 1 insemination as compared with 2 alternate day inseminations with timing based on previous cycle length and basal body temperature changes. The study involved 60 patients who underwent a total of 264 therapeutic donor insemination cycles using cryopreserved semen specimens. Patients alternated LH-kit timed cycles with cycles timed by non-LH methods for a total of 6 cycles or until pregnancy was achieved. Fecundability rates were 12.3% for LH-kit cycles and 5.3% for non-LH method cycles. The difference in outcome was not statistically significant. However, when the LH kit plus 1 insemination was compared with 2 inseminations timed by conventional methods, there appeared to be a distinct monetary and time expenditure advantage. These findings suggest that sufficient advantage may be derived from use of an LH kit to recommend its use on a routine basis for the timing of therapeutic donor insemination. PMID- 2204554 TI - Sperm bound to zona pellucida in hemizona assay demonstrate acrosome reaction when stained with T-6 antibody. AB - A monoclonal antibody, T-6, useful for detecting acrosome-reacted sperm based on an immunofluorescent assay, was employed to evaluate acrosomal status of human sperm that were tightly bound to hemisected human zonae pellucidae (hemizona assay). Over 90% of the bound sperm evaluated exhibited immunofluorescent patterns indicative of acrosome reaction. This staining method for evaluating the acrosomal status of sperm bound to the zona pellucida may enable definition of a group of male infertility patients heretofore not recognized. PMID- 2204555 TI - Gonadotropin-releasing hormone therapy analog and migraine? PMID- 2204557 TI - Diagnosis and non-surgical treatment of extrahepatic biliary obstruction. PMID- 2204556 TI - [Analysis of islet cell surface antigen reactions with islet cell surface antibodies (ICSA)]. AB - Islet cell surface antibodies (ICSA) have been detected in the sera of many patients with insulin-dependent diabetes mellitus (IDDM). They have also been demonstrated to affect the plasma membranes of beta-cells in vitro. To determine the pathogenetic role of ICSA in IDDM, we studied their prevalence and their relationship to lymphoblastogenesis (LBG) in diabetes as well as in other autoimmune diseases. Furthermore, islet cell antigens (IAg) were characterized from rat pancreatic islet cells, using an affinity column consisting of human IgGs including ICSA. ICSA titers were measured by indirect immunofluorescence. Sera were determined as ICSA-positive when they reacted to more than 10% of 50 100 cells. The LBG investigation was carried out after a 4-day incubation with phytohemagglutinin (PHA), pokeweed mitogen (PWM), or concanavalin A (Con A). The LBG induced by IAg was investigated after an 8-day incubation. Lymphocytes included 75% CD3-positive cells and 5% CD20-positive cells. IAg were purified from ICSA-positive IgG coupled to CNBr-activated sepharose 4B. The prevalence of ICSA was 39% in patients with IDDM (11/28), 15% in non-insulin dependent diabetes mellitus (NIDDM) (16/109), 14% in Graves' disease (3/22), 29% in Hashimoto's disease (5/17), 12% in rheumatoid arthritis (3/25), 20% in systemic lupus erythematosus (SLE) (7/35), and 33% in Sjogren's syndrome (2/6). No ICSA were detected in 27 normal subjects. Although sera from the patients with autoimmune diseases contained antinuclear antibodies, antithyroid antibodies and/or rheumatoid factor, there was no relationship between the prevalence of such antibodies in patients with ICSA and those without it. In 3 patients (60%) with ICSA-positive IDDM, the lymphoblastogenic responses to PHA and PWM were decreased. A similar decrease was observed when comparing ICSA-positive NIDDM to ICSA-negative NIDDM (PHA: p less than 0.05; PWM: p less than 0.01). However, there was no relationship between HbA1 and the LBG response or between HbA1 and the presence of ICSA. The relative molecular weights (Mr.) of the IAg reacting with ICSA-positive IgG were around 67, 64, 55, and 20K in all but three patients with diabetes mellitus. IAg with a Mr. around 30K or less than 14K were also demonstrated in some patients with diabetes mellitus. The Mr. of IAg was the same in three patients with autoimmune disease as in diabetes mellitus, but it differed in three other similar patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2204558 TI - Federal official says: "be a bad doctor". PMID- 2204559 TI - The eosinophilia-myalgia-syndrome and L-tryptophan containing products: a case report and review of the literature. PMID- 2204560 TI - Demographic seasonality and development: the effects of agricultural colonialism in Taiwan, 1906-1942. AB - Nearly all developed countries have experienced dramatic declines in the seasonality of demographic behavior over the last century. This article examines seasonal behavior in the population of Taiwan between 1906 and 1942, during Japanese colonial rule. First, we analyze seasonal demographic cycles and their ties to the cultural calendar and agriculture. Second, we compare seasonality in two regions (Xinzhu and Tainan) that experienced different agricultural development under the colonial regime. Findings demonstrate that demographic seasonality was less pronounced when urban development and colonial agricultural intensification produced more heterogeneous seasonal patterns of labor. We find that changes in agricultural organization, rather than purely a shift to nonagricultural production, may significantly reduce established seasonal timing of demographic behavior. PMID- 2204561 TI - [Automated "data base" prediction of surgico-orthodontic results. 2]. PMID- 2204563 TI - [Prosthetic therapy in geriatrics. 1]. PMID- 2204562 TI - [Restoration of a fractured incisor with recovery of the fragment]. AB - The Authors propose the functional and estetical maintenance of a maxillary incisor, which presents a third class traumatic break, as Ellis opinion. After the positive exit, offered by the partial pulpotomy intervent, effected in order to keep on saving the vitality of the element, the same one was built again, putting on the original incisor fragment, recuperated by the restaurating operation, concerning on composed materials. After twenty-four months the Authors present the clinic control. PMID- 2204565 TI - [Composites for anterior restoration. Clinical report]. AB - The Authors, after a short description of the characteristics of composite materials used for restoration of anterior teeth, present clinical cases to demonstrate the improvement of such filling materials. The use of composite is increased even if the dentists should proceed with caution in order to obtain good and lasting results. PMID- 2204564 TI - [Cast gold inlay. A reliable and effective restoration]. AB - The Authors want to repropose a technique which is one of the earliest used in conservative dentistry: the fused-gold reconstruction. A method of easy application is explained by the Authors and will undoubtedly stimulate the dentists' interest towards this kind of reconstruction which still today represents one of the most efficient solutions, in conservative dentistry, of the first and second class cavities. PMID- 2204566 TI - [Removable provisional dentures with wire clasps]. AB - The matter examined regards the possible prosthetic therapies in temporary emergency situations following paradontopathic tooth extractions, of which comparisons are made between the positive and negative aspects of realizable therapeutic processes. Considering the advantages of the type of prosthetic therapy chosen, the Author describes the entire therapeutic process, both clinical and technical, emphasizing its methodology and the equipment and materials required, which make it possible for the doctor himself to put it immediately into practice in his office. PMID- 2204567 TI - [Comparative study of fine needle aspiration and large caliber needle biopsy under echographic control for the diagnosis of abdominal tumors]. AB - The aim of this study was to compare the results of fine needle aspiration (22 G) with large caliber needle biopsy (18 G) in patients suspected of having abdominal malignancy. From November 1988 to December 1989, 73 patients aged 32 to 78 years (mean 66 years), suspected sonographically of having hepatic malignancy (66 cases) or extrahepatic tumors (7 cases), underwent ultrasonography guided percutaneous fine needle aspiration (22 G) and biopsy with a large caliber needle (18 G). There were no complications. Overall sensitivity for diagnosis of malignancy was significantly better (p less than 0.01) with 18 G needle biopsies (91.2 percent) than with fine needle cytology (71.4 percent). Specificity was 100 percent. The distinction between primary and secondary malignant tumor was possible in 87.5 percent with the large caliber needle and in only 42.9 percent with the fine needle (p less than 0.001). Histological findings were adequate hepatic metastases in 86.5 percent with the 18 gauge needle and in 51.4 percent with the 22 gauge needle (p less than 0.001). In the 7 extra-hepatic tumors, the 18 G biopsy was always positive whereas fine needle cytology was positive in only 5 out of 7 cases. Correct diagnosis for benign diseases was possible in 7 out of 10 cases with the large caliber needle whereas the fine needle cytology was always negative. These results show the superiority of large caliber needle (18 G) compared to fine needle (22 G) guided punction for both diagnosis of malignancy and origin of the tumor. Complications did not occur more frequently than with fine caliber needles. PMID- 2204568 TI - [Eosinophilic infiltrates of the gastrointestinal tract]. PMID- 2204570 TI - [Achalasia associated with gastric leiomyoma. The value of endoscopic sonography]. PMID- 2204569 TI - [Cavernous lymphangioma of the liver. A report of 2 cases and review of the literature]. AB - The authors report 2 cases of hepatic lymphangioma observed in a 54-year-old woman, and in a 39-year-old man. These tumors were discovered upon ultrasound examination performed for jaundice due to viral hepatitis, and for abdominal right upper quadrant pain respectively. Computed tomography and angiography showed hypervascularized tumors. Diagnosis was established through surgical biopsy specimens. The clinical course was uneventful, during respectively the 9- and 3-year follow-up periods, respectively. From these and the 40 previously reported cases, the authors describe the different features of this unusual tumor. PMID- 2204571 TI - Expression in Escherichia coli of the carboxy terminal domain of the BLAR sensory transducer protein of Bacillus licheniformis as a water-soluble Mr 26,000 penicillin-binding protein. AB - A cloning vector has been constructed which allows production and export by Escherichia coli of the Met346-Arg601 carboxy terminal domain of the 601 amino acid BLAR sensory-transducer involved in beta-lactamase inducibility in Bacillus licheniformis. The polypeptide, referred to as BLAR-CTD, accumulates in the periplasm of E. coli in the form of a water-soluble, Mr 26,000 penicillin-binding protein. These data and homology searches suggest that BLAR has a membrane topology similar to that of other sensory-transducers involved in chemotaxis. PMID- 2204572 TI - A major outer membrane protein of Serratia marcescens which was easily solubilized and had a capacity to bind to calcium. AB - Easily solubilized major outer membrane protein was found in Serratia marcescens. The protein was originally obtained as a membrane-associated, insoluble protein in the outer membrane when the cells were slightly disrupted. However, the amount of this protein in the outer membrane gradually decreased with the time of sonication. The decrease was not due to decomposition of the protein but to solubilization into a soluble fraction after a long period of disruption. The molecular weight of this protein was 47 kDa and it bound calcium. Another 40 kDa calcium binding protein was also found in the outer membrane of S. marcescens. PMID- 2204573 TI - Cloning of the type VII trimethoprim-resistant dihydrofolate reductase gene and identification of a specific DNA probe. AB - A 1.3 kb HindIII fragment encoding the type VII trimethoprim-resistant dihydrofolate reductase gene was cloned into pBR322. Unidirectional deletion of this cloned fragment with exonuclease III identified the start of the dihydrofolate reductase gene. An internal 300bp EcoRV fragment was identified which could be used as a specific non-radioactive DNA probe to distinguish bacteria carrying the type VII gene from those carrying genes encoding other known dihydrofolate reductase types. PMID- 2204574 TI - Antibacterial activity of phosphono dipeptides based on 1-amino-1 methylethanephosphonic acid. AB - Phosphono dipeptides containing 1-amino-1-methylethanephosphonic acid (phosphonic acid analogue of alpha-methylalanine, MeAlaP) and glycine, alanine, valine, leucine phenylalanine, proline, methionine or lysine as N- terminal component were synthesized in order to determine their antibacterial properties. Peptides containing alanine, leucine, valine phenylalanine and methionine showed marked in vitro activity, especially against Escherichia coli and Serratia marcescens strains. There were, however, generally less potent than the respective phosphono dipeptides based on 1-aminoethanephosphonic acid (phosphonic acid analogue of alanine, AlaP). The possible mechanism of action of the peptides of MeAlaP involves their active transport into the bacterial cell, followed by intracellular release of MeAlaP, which most likely inhibits alanine racemase, a key enzyme in peptidoglycan biosynthesis. Studies on the uptake of AlaMeAlaP and LeuMeAlaP by Escherichia coli mutants defective in the oligopeptide permease suggest that these peptides are not transported by the oligopeptide transport system. PMID- 2204575 TI - Transmission of killer activity into laboratory and industrial strains of Saccharomyces cerevisiae by electroinjection. AB - The killer character was electrically introduced into protoplasts of three yeast strains. These were the killer-negative variant of the K1 killer strain Saccharomyces cerevisiae T 158 C (his-); the killer-sensitive laboratory strain S. cerevisiae AH 215 (leu-, his-); and the killer-sensitive industrial strain S. cerevisiae AS 4/H2 (rho-). The killer dsRNA used for electroinjection was isolated from the super-killer strain S. cerevisiae T 158 C. Optimum numbers of transformed cells were obtained after regeneration and selection in appropriate media if the protoplasts were exposed to three exponentially decaying field pulses of 18.2 kV/cm strength and 40 microseconds duration at 4 degrees C. In the case of the killer-negative variant of S. cerevisiae T 158 C the majority of the protoplasts were transformed, whereas in the case of the two other strains the yield of transformed clones was much less. This latter result is expected if the expression of the electroinjected dsRNA was diminished in these two strains. Gel electrophoresis of the dsRNA of the clones of the three strains supported the conclusion that the transformed clones exhibited killer activity. The transformed clones of all three species were stable. PMID- 2204577 TI - Mapping functions. PMID- 2204576 TI - Cloning and nucleotide sequences of the mdh and sucD genes from Thermus aquaticus B. AB - A 3 kb DNA fragment containing the gene (mdh) encoding malate dehydrogenase (MDH) from the thermophile Thermus aquaticus B was cloned in Escherichia coli and its nucleotide sequence determined. Comparative analysis showed the nucleotide sequence to be very closely related to that determined for the Thermus flavus mdh gene and flanking regions, with no differences between the predicted amino acid sequences of the MDHs. A proximal open reading frame, identified as the sucD gene, and the mdh gene may be parts of the same operon in T. aquaticus B. Expression of the T. aquaticus B mdh gene in E. coli was found to be at a relatively low level. A simple method for purification of thermostable MDH from the E. coli clone containing the T. aquaticus B mdh gene is presented. PMID- 2204578 TI - Analysis of sequence elements important for expression and regulation of the adenylate cyclase gene (cya) of Salmonella typhimurium. AB - We determined the nucleotide sequence of the regulatory region of the cya gene of Salmonella typhimurium. A set of nested BAL-31 deletions originating upstream of the promoter/regulatory region and extending into the cya structural gene was constructed in M13mp::cya phages and was tested for complementation of a chromosomal cya deletion mutation. BAL-31 deletion mutants unable to complement cya localized the major cya promoter. The synthetic tac promoter was inserted upstream of the BAL-31 deletions so that expression of cya was dependent on transcription from tac. Those tac derivative phages unable to complement cya localized the translation initiation region. The cya DNA sequence revealed at least three potential promoters capable of transcribing cya, with a CRP binding site straddling the-10 hexamer of the promoter proximal to the structural gene. The leader RNA sequence initiated at the latter promoter is approximately 140 bases long and includes a region that may form a stable secondary structure (delta G = -23.8 kcal). There exist two possible in-frame translation start points, one of which is TTG and the other of which is ATG. The sequence of the S. typhimurium regulatory region was compared with that reported for Escherichia coli. PMID- 2204579 TI - "Alternative self-diploidization" or "ASD" homothallism in Saccharomyces cerevisiae: isolation of a mutant, nuclear-cytoplasmic interaction and endomitotic diploidization. AB - A mutant of Saccharomyces cerevisiae representing a novel life cycle, named "alternative self-diploidization" or "ASD" homothallism, was obtained fortuitously. In this life cycle, MAT alpha (or MATa) haplophase and MAT alpha/MAT alpha (or MATa/MATa) diplophase alternate. Germinated cells are haploid and mating. They soon become nonmating and sporogenous as they vegetatively grow. They sooner or later diploidize presumably via endomitosis. The diploid cells haploidize via normal meiosis. A single recessive nuclear mutation, named asd 1 1, is responsible for "ASD" homothallism. In the rho 0 cytoplasm, asd 1-1 cells mate even if at a low efficiency and fail to diploidize. Since pet mutations do not have such effects, we conclude that a certain mitochondrial function other than respiration is required for manifestation of "ASD" homothallism. That is, "ASD" homothallism is the result of some sort of nuclear-cytoplasmic interaction. PMID- 2204580 TI - Isolation and characterization of PEP5, a gene essential for vacuolar biogenesis in Saccharomyces cerevisiae. AB - pep5 mutants of Saccharomyces cerevisiae accumulate inactive precursors to the vacuolar hydrolases. The PEP5 gene was isolated from a genomic DNA library by complementation of the pep5-8 mutation. Deletion analysis localized the complementing activity to a 3.3-kb DNA fragment. DNA sequence analysis of the PEP5 gene revealed an open reading frame of 1029 codons with a calculated molecular mass for the encoded protein of 117,403 D. Deletion/disruption of the PEP5 gene did not kill the cells. The resulting strains grow very slowly at 37 degrees. The disruption mutant showed greatly decreased activities of all vacuolar hydrolases examined, including PrA, PrB, CpY, and the repressible alkaline phosphatase. Apparently normal precursors forms of the proteases accumulated in pep5 mutants, as did novel forms of PrB antigen. Antibodies raised to a fusion protein that contained almost half of the PEP5 open reading frame allowed detection by immunoblot of a protein of relative molecular mass 107 kD in extracts prepared from wild-type cells. Cell fractionation showed the PEP5 gene product is enriched in the vacuolar fraction and appears to be a peripheral vacuolar membrane protein. PMID- 2204581 TI - Genetic evidence for preferential strand transfer during meiotic recombination in yeast. AB - During meiotic recombination in the yeast Saccharomyces cerevisiae, heteroduplexes are formed as an intermediate in the exchange process. In the formation of an asymmetric heteroduplex, one chromosome acts as a donor of a single DNA strand and the other acts as a recipient. We present genetic evidence that the nontranscribed strand is donated more frequently than the transcribed strand in spores that have an unrepaired mismatch at the HIS4 locus. PMID- 2204583 TI - [A concept of limiting genetic factors of expression, organization, and evolution]. AB - Elicitation and analysis of limiting genetic factors represent convenient method for approximate description of complex molecular-genetic systems. In sequential metabolic ways, the limiting is based on the minimum of catalytic activity, in parallel ones--on the maximum activity. In polygenic systems, the expressing polygenes affect always the limiting oligogenes. Limiting genes are only available to selection on the population level, the non-limiting genes being neutrally evolving. This result eliminates the acuteness of the Haldane's dilemma. The complex genetic systems could be quickly evolving by relay-race principle with sequentional change of limiting genes and without violation of Haldane's dilemma. The limiting factors of organization which restrict the possibilities of some special evolutionary directions have the key role in evolution. These limits were historically overcome by acceptance of evolutionary acquirements of wide usage. The sequence of such limits and acquirements was assumed as a basis of "scenario" of Prebiological and Biological Molecular Evolution. The concept is illustrated by some examples and results of theoretical analysis. PMID- 2204582 TI - Mitotic transmission of artificial chromosomes in cdc mutants of the yeast, Saccharomyces cerevisiae. AB - In the yeast, Saccharomyces cerevisiae, cell division cycle (CDC) genes have been identified whose products are required for the execution of different steps in the cell cycle. In this study, the fidelity of transmission of a 14-kb circular minichromosome and a 155-kb linear chromosome fragment was examined in cell divisions where specific CDC products were temporarily inactivated with either inhibitors, or temperature sensitive mutations in the appropriate CDC gene. All of the cdc mutants previously shown to induce loss of endogenous linear chromosomes also induced loss of a circular minichromosome and a large linear chromosome fragment in our study (either 1:0 or 2:0 loss events). Therefore, the efficient transmission of these artificial chromosomes depends upon the same trans factors that are required for the efficient transmission of endogenous chromosomes. In a subset of cdc mutants (cdc6, cdc7 and cdc16), the rate of minichromosome loss was significantly greater than the rate of loss of the linear chromosome fragment, suggesting that a structural feature of the minichromosome (nucleotide content, length or topology) makes the minichromosome hypersensitive to the level of function of these CDC gene products. In another subset of cdc mutants (cdc7 and cdc17), the relative rate of 1:0 events to 2:0 events differed for the minichromosome and chromosome fragment, suggesting that the type of chromosome loss event observed in these mutants was dependent upon chromosome structure. Finally, we show that 2:0 events for the minichromosome can occur by both a RAD52 dependent and RAD52 independent mechanism. These results are discussed in the context of the molecular functions of the CDC products. PMID- 2204584 TI - [Nuclear protein factors binding with specific DNA sequences]. AB - Primary structure of thousands of genes is being determined in many laboratories worldwide. While it is relatively easy to analyse the coding region(s) of genes, it is usually hard to understand what is located in non-coding regions. A non coding region may contain very valuable information about the mode of functioning of a given gene, e. g. promoters, enhancers, silencers etc. The regulatory function of these sequences is determined by their interaction with certain sequence-specific proteins, i. e. the presence of a certain DNA sequence in a non coding region of a gene may suggest that the gene is regulated by a specific protein factor. This minireview summarizes recent data on most known eukaryotic sequence-specific DNA-binding protein factors, including their origin, DNA consensus, and their role in expression of corresponding genes. PMID- 2204586 TI - Risk factors for geriatric stroke: identification and follow-up. AB - Systolic or diastolic hypertension, cigarette smoking, diabetes mellitus, left ventricular hypertrophy, age, prior stroke, transient cerebral ischemic attack, extracranial arterial disease, and coronary heart disease are risk factors for the most common type of geriatric stroke, atherothrombotic brain infarction (ABI). Also, by contributing to hypertension and diabetes mellitus, obesity predisposes to ABI. The relationship of abnormal serum lipids and of physical inactivity to ABI is unclear. Antihypertensive treatment decreases the incidence of fatal and nonfatal stroke in patients with systolic and diastolic hypertension. Cessation of smoking also decreases risk. PMID- 2204585 TI - Diabetic neuropathies in the elderly: management update. AB - Diabetic neuropathy is a common, varied, and disabling disease that is potentially responsive to therapy. While its pathogenesis is as yet unclear, its clinical presentations and natural history are well known. Present information suggests glycemic control can prevent neuropathy and in some cases cause established neuropathy to regress. Drug therapy is useful only for painful neuropathy. Avoidance of alcohol and behavioral and surgical relief of nerve entrapment are helpful in certain cases. PMID- 2204587 TI - 'Failure to thrive' in the elderly: diagnosis and management. AB - "Failure to thrive" (FTT) is a term used to describe a gradual decline in physical and/or cognitive function of an elderly patient, usually accompanied by weight loss and social withdrawal, that occurs without immediate explanation. Both age-related and sociodemographic factors predispose the elderly to FTT. The most common etiologies are dementia, depression, delirium, drug reactions, and a few chronic diseases. The diagnostic evaluation of patients with FTT includes a review of the patient's activities of daily living, cognitive function, and mood; a targeted history and physical examination; and selected laboratory studies. Early recognition and management of FTT can reduce the risk of further functional deterioration, hospitalization, or nursing home placement. PMID- 2204588 TI - Cosmetic modalities for aging skin: what to tell patients. AB - Skin changes associated with aging often manifest as cosmetic disabilities. As the population of elderly persons continues to rise, these aging skin changes and patients' dissatisfaction with them will increasingly command the attention of the primary care physician. The cosmetic aging changes and management strategies addressed here include wrinkles, hair changes, common benign neoplasms, dyspigmentation, and telangiectasias. While none of these conditions is a direct threat to the physical well being of the patient, their psychological impact, particularly with regard to self-perception, can be significant and even profound. They therefore merit a response from physicians caring for such patients. PMID- 2204589 TI - [Epidemiological role of food products in spreading Shigella infections in present-day conditions]. PMID- 2204590 TI - [Computer assisted evaluation of the status of professionally important functions of an operator]. PMID- 2204591 TI - [Effect of ultraviolet irradiation on calcium, sodium and potassium levels in albino rats]. AB - Data presented by the authors testifies to the fact that neither 2 weeks, nor one month after the 10-day course of ultraviolet irradiation (UVR) with an intensity from 1/4 up to 2 biodoses daily changes in calcium, sodium and potassium content in blood serum of laboratory animals (white rats) were detected. At the same time, 2 weeks following the cessation of UVR course a tendency towards calcium accumulation in the whole organism of laboratory animals was observed, which was most noticeable+ after daily 10-day exposure to UVR with an intensity from 1/2 up to 1 biodose. The tendency was still present one month following the termination of UVR course. The total sodium and potassium store in the whole organism of laboratory animals did not practically change either immediately, or 2 weeks, or 1 month after the termination of 10-day UVR course with the intensity from 1/4 to 2 biodoses daily. PMID- 2204592 TI - [Biotransformation of xenobiotics--detoxication or intensification of their toxicity ? (review of the literature)]. PMID- 2204593 TI - Serum erythropoietin activity following kidney transplantation. AB - 31 patients with successful kidney grafts were studied. Ep, Ht, Hb and T lymphocytes were determined. Native and grafted kidneys were studied by ultrasonography. After KT, 45% of patients had PTE and in 71% of these a spontaneous regression was observed. Mean serum Ep activity in patients with and without PTE was significantly higher than in healthy controls. Different erythroid colony growth sensibility and responsiveness to higher serum Ep (PTE and non-PTE patients) may be due to T3 cell interaction with BFU-E. PMID- 2204594 TI - Chemotherapy of adult acute nonlymphoblastic leukaemia. AB - Seventy-two consecutive and previously untreated adults with acute non lymphoblastic leukaemia (ANLL), having a median age of 36 years (range 12 to 71), were prospectively randomised to receive conventional doses of cytosine arabinoside and doxorubicin combined with either etoposide (CTR III) or 6 thioguanine (DAT). Morbidity was comparable between the two regimens and complete remission (CR) rates of 52% and 62% respectively (p greater than 0.50) were not influenced by age above or below 50 years, initial white cell count, French American-British classification, or race. However, growth pattern in the GM: CFUc assay was found to identify a subgroup of patients who had a significantly higher CR rate. Similarly, the secretion of tissue plasminogen activator by leukaemic blasts in vitro uniformly predicted for primary drug resistance, whereas a CR rate of 68% was associated with production of the urokinase type or a mixture of both enzymes. Remission duration and survival did not differ between these two forms of chemotherapy, nor were they influenced by immunotherapy with C. parvum or the duration of maintenance therapy, whereas age below 50 and the species of plasminogen activator secreted were significant prognostic factors. It is concluded that etoposide can be substituted for 6-thioguanine in these cytosine arabinoside and doxorubicin-containing regimens and that for both combinations the most sensitive prognostic factor for CR and survival is the species of plasminogen activator secreted in vitro by the leukaemic blasts. PMID- 2204596 TI - [The small intestine as an immune organ]. AB - The immune system of the gastrointestinal tract (gut-associated lymphoid tissue- GALT) differs from the peripheral immune system in a number of points, and can also react largely independently of the latter. The lymphatic cells of GALT are both strictly compartmentalized (Peyer's patches, lymphatic follicles), and diffusely distributed within the mucosa. The organized lymphatic tissue represents the afferent component, the diffuse lymphatic tissue the efferent component, of the intestinal immune response. A marked recirculation behavior (homing) of the intestinal lymphocytes makes it clear hat GALT is simply part of a more comprehensive common mucosal immune system, the mucosa-associated lymphatic tissue (MALT). At the center of a description of the pathophysiology of the small bowel as an immune organ is Crohn's disease. By way of example, current immunological aspects of immunoregulation, specific and unspecific cytotoxic, that is, tissue-injurious, immune reactions, as well as immunoglobulin isotype and immunoglobulin G subclass differentiation are discussed. PMID- 2204595 TI - E. coli antibodies do not cause false-positivity in recombinant anti-HIV assays. AB - 129 sera with known antibody titres against E. coli 026 and E. coli 055 strains were tested with the Abbot second generation anti-HTLV III recombinant screening assay. No difference in the O.D. values was found between sera with high, normal and low anti-E. coli titres. In addition, no false-positive reactions were observed with the anti-HIV negative sera containing E. coli antibodies in high titres in a Western blot assay in which recombinant env antigen was applied. These results suggest that E. coli assays in which E. coli-produced recombinant antigens are used. PMID- 2204597 TI - [Chemotherapy of opportunistic infections in AIDS]. AB - Proposal for therapy and prophylaxis of opportunistic infections in AIDS using complex combinations consisting of four substances (Rifampicin + Sulfamethoxazol + Trimethoprim + Isoniazide or Rifampicin + Sulfamethoxazol + Trimethoprim + Protionamide) in a fixed combination. PMID- 2204598 TI - [Treatment of hyperlipoproteinemia in patients with diabetes mellitus]. AB - In a large percentage of cases, diabetes mellitus leads to hyperlipidemia. In addition to the diabetes-related secondary hyperlipidemias, all types of primary disturbances of lipid metabolism can also be observed in diabetics. Depending upon the degree of severity and type of metabolic disorder presenting, not only suitable dietetic treatment, but also the various lipid-lowering drugs, fibrates, nicotinic acid, probucol, cholestyramine and the HMG-CoA reductase inhibitors should be introduced into therapy. As in all groups with an elevated coronary risk, strict management of the lipid levels is mandatory in diabetics, too. PMID- 2204599 TI - [Diabetic nephropathy. Pathogenetic, diagnostic and therapeutic concepts]. AB - Today the clinical picture of diabetes mellitus is often determined by its late complications. Diabetic nephropathy appears in about 40% of all diabetic patients with type 1 (insulin-dependent) diabetes mellitus within a period of 10-15 years. Early diagnosis is crucial for the prognosis as appropriate therapy may delay or even arrest the reduction of filtration fraction and terminal renal failure. Most important for the early diagnosis is the measurement of albumin and protein excretion. PMID- 2204600 TI - [Corneal transplantation]. AB - After a brief review of the history of corneal grafting, consideration is given to the topics immunology, and the harvesting and preservation of donor material. The surgical techniques of lamellar and penetrating keratoplasty are briefly discussed. The indications for perforating and lamellar keratoplasty are listed, and the prognosis associated with the individual indications considered. Current problems of corneal grafting are the increasing numbers of operations, the question of the significance of HLA typing, and the evaluation of postoperative immunosuppression with cyclosporine A. PMID- 2204601 TI - [Chronic conjunctivitis]. AB - The etiology, clinical picture, diagnosis and treatment of chronic inflammatory diseases of the conjunctiva are described. It is emphasized that, despite the respective specific etiology, the symptomatology has common factors, treatment is difficult and all too often only symptomatic, and chronic inflammatory diseases of the conjunctiva sooner or later lead to the so-called dry eye syndrome. PMID- 2204602 TI - Immune responses to insulin and lymphocyte subclasses at diagnosis of insulin dependent diabetes and one year later. AB - Insulin induced proliferation of blood mononuclear cells, numbers of blood B and T cells, of blood lymphocytes bearing interleukin 2 receptors or HLA class II molecules were assayed at diagnosis and one year later in children with insulin dependent diabetes mellitus (IDDM) and in healthy children. Insulin and islet cell antibodies were also studied. The numbers of lymphocytes expressing HLA class II molecules and NK cells were increased at diagnosis. T cells of the helper/inducer (CD4+) phenotype and interleukin 2 receptor positive lymphocytes were increased both at diagnosis and one year later. At diagnosis, insulin induced proliferation of blood mononuclear cells in 65% and one year later in 50% of the patients. Insulin antibodies were detected in 10% and islet cell antibodies in 90% of patients at diagnosis, and in 67% and 78%, respectively, one year later. PMID- 2204603 TI - Sickle cell anaemia presenting as periorbital tumour--case report. PMID- 2204604 TI - Caregivers for Alzheimer's patients: what we are learning from research. AB - The research literature on adjustment by family members to providing care to victims of Alzheimer's disease is new and expanding rapidly. The purpose of this review is to summarize the categories and methods of that research; to evaluate critically the state of knowledge these studies are producing; and to suggest ways of strengthening future investigations. The review is organized around psychological, social, and health factors as antecedents or correlates of similar categories of outcomes for caregivers. While there are some emerging relationships involving caregiver burden, depression, and psychological well being, it is difficult to generalize about the determinants or correlates of the consequences of meeting caregiver responsibilities; this difficulty probably results from a failure to deal adequately with key concepts and circumstances of the caregiver. These conceptual and methodological shortcomings are discussed and suggestions for refinement made. PMID- 2204605 TI - Recent developments in UVA photoprotection. PMID- 2204606 TI - Electrical stimulation of skin. PMID- 2204607 TI - The isomorphic response of Koebner. PMID- 2204608 TI - The use of thermal baths in the treatment of skin disease in old-time Ethiopia. PMID- 2204609 TI - The role of the gut in water balance. PMID- 2204610 TI - An empirical investigation of the nature of hospital mission statements. AB - An exploratory study of hospital planners was completed to determine if there was agreement between theory and practice concerning mission statement components and development. Results showed that mission statements have received little attention as part of the overall strategic planning process. PMID- 2204611 TI - Total quality management in health: making it work. AB - Many health organizations are trying total quality management (TQM). This approach represents a total paradigm shift in health care management and presents a series of potential conflict areas in the way health organizations are managed. These areas include TQM's participatory approach versus professional and managerial authority, collective versus individual responsibility, quality assurance and standards versus continuous improvement, and flexible versus rigid objectives and plans. This article reviews the areas of conflict and suggests a number of action guidelines for the successful implementation of TQM. PMID- 2204613 TI - Thoracic outlet syndrome--a myofascial variant: Part 1. Pathology and diagnosis. AB - Four cases of thoracic outlet syndrome are described, with observations to support a primary myofascial etiology involving the scalene and smaller pectoral muscles. It is believed that thermography can be extremely helpful as an aid in diagnosis of thoracic outlet syndrome and, when combined with Doppler blood flow studies and photoplethysmography, can help localize the site of the pathosis. Thermography is a sensitive, non-invasive test that most clearly demonstrates pathology in the hand views. Global changes throughout the entire hand suggest vascular or reflex autonomic involvement, while a more dermatomal distribution suggests specific neurologic involvement. Vigorous stretching and a unique form of myofascial release manipulation has been successful in rapidly treating patients with thoracic outlet syndrome. Follow-up thermography (perhaps hand and forearm views only) can be used to monitor response to treatment and to objectively document improvement. PMID- 2204612 TI - Searching for clues to the origins of OMT. PMID- 2204614 TI - Virulence factors in motile Aeromonas species. PMID- 2204615 TI - F-specific RNA bacteriophages and sensitive host strains in faeces and wastewater of human and animal origin. AB - Faeces of humans, pigs, cattle and chickens were investigated for the presence of somatic coliphages, F-specific bacteriophages and Escherichia coli strains sensitive to infection by F-specific phages. Attention was given to the possible effect of age and use of antibiotics on the prevalence of the FRNA phages and sensitive E. coli strains. Somatic coliphages were often detected in high numbers in all types of faeces. In contrast, FRNA phages were rarely detected in faeces from humans and cattle but more often in faeces from pigs and adult chickens. Samples from young chickens (with or without antibiotics) were consistently positive for FRNA phages (up to 3 x 10(6) pfu/g). F-specific RNA phages were found in substantial numbers (greater than 10(3) pfu/ml) in a variety of wastewaters: domestic, hospital, slaughterhouses and occasionally in 'grey water'. Their origin in wastewater was not clear. Strains from faeces usually belonged to serogroups I and IV. These types were also found in wastewater, as were group II and III strains. Serogroup II phages were abundant in wastewater of human origin but rare in faeces. Escherichia coli strains sensitive to infection by F-specific phages were common in faeces (overall 290/1081: 27%). No strains with fully depressed F-pilus synthesis were detected among the sensitive strains. It is concluded that the occurrence of F-specific RNA bacteriophages in water points to sewage pollution rather than faecal pollution; the mechanism of replication of these organisms in wastewater is not understood. PMID- 2204616 TI - Purification and properties of recombinant rat catalase produced in Escherichia coli. AB - Catalase is a characteristic enzyme of peroxisomes. To study the molecular mechanisms of the biogenesis of peroxisomes and catalase in a less complex system than rat liver cells, we expressed recombinant rat catalase in Escherichia coli, which has no peroxisomes. The concentration of recombinant catalase produced in E. coli transformed with the expression vector carrying the complete coding region of rat catalase cDNA was about 0.1% of the total soluble protein. The recombinant catalase was purified by DEAE-cellulose column chromatography followed by acidic ethanol precipitations. The properties of rat liver catalase and those of the recombinant were similar with respect to molecular mass, catalytic properties, profiles of absorption spectra, and iron contents. The NH2 terminal amino acid sequence of the purified recombinant catalase, as determined by Edman degradation, was in complete agreement with the amino acid sequence predicted from the nucleotide sequence of rat catalase cDNA, except that the first initiator methionine was not detected. The COOH-terminal amino acid sequence was determined by carboxypeptidase A digestion and the sequence, -Ala Asn-Leu-OH, matched the predicted COOH-terminal amino acid sequence of rat catalase. Recombinant rat catalase gave almost the same multiple protein bands on native polyacrylamide gel isoelectric focusing as observed with authentic rat liver catalase. PMID- 2204617 TI - Allosteric properties, substrate specificity, and subsite affinities of honeybee alpha-glucosidase I. AB - The substrate specificity of honeybee alpha-glucosidase I, a monomeric enzyme was kinetically investigated. Unusual kinetic features were observed in the cleavage reactions of sucrose, maltose, p-nitrophenyl alpha-glucoside, phenyl alpha glucoside, turanose, and maltodextrin (DP = 13). At relatively high substrate concentrations, the velocities of liberation of fructose from sucrose, glucose from maltose, p-nitrophenol from p-nitrophenyl alpha-glucoside, and phenol from phenyl alpha-glucoside were accelerated, and so the Lineweaver-Burk plots were convex, indicating negative kinetic cooperativity: the Hill coefficients were calculated to be 0.50, 0.64, 0.50, and 0.67 for sucrose, maltose, p-nitrophenyl alpha-glucoside, and phenyl alpha-glucoside, respectively. For the degradation of turanose and maltodextrin, the enzyme showed a sigmoidal curve in v versus s plots and thus catalyzed the reaction with positive kinetic cooperativity. The Lineweaver-Burk plots were concave and the Hill coefficients were 1.2 and 1.5 for turanose and maltodextrin, respectively. These unique properties cannot be interpreted by the reaction mechanism that Huber and Thompson proposed: (1973) Biochemistry 12, 4011-4020. The rate parameters for the hydrolysis of sucrose, maltose, p-nitrophenyl alpha-glucoside and phenyl alpha-glucoside were estimated by extrapolating the linear part of the Lineweaver-Burk plots at low substrate concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2204618 TI - DNase I footprinting analysis of RecA protein polymerized on DNA during strand exchange reaction between a gapped circle and a linear duplex. AB - RecA protein mediates homologous pairing and strand exchange reactions between a circular duplex with a single strand gap and a linear duplex. We have used the DNase I footprinting method to analyze processes involving four strands during these reactions. We asked how the length of DNA protected by RecA protein changes as these reactions proceed. We compared two kinds of gapped DNAs. We found that RecA protein polymerizes rapidly in the forward direction (5' to 3' with respect to the single strand). We found, however, that polymerization in the reverse direction was more prominent with a duplex carrying a longer gap than one carrying a shorter gap. DNase I footprints showing protection by RecA protein were obtained only at limited nuclease concentrations, which in turn depended on the position of the end label and the stage of the strand exchange reaction. As judged by the concentrations of DNase I good for footprinting, the extent of protection by RecA protein was greatest for (+) single-stranded DNA at its first binding site, next highest for heteroduplex containing this (+) strand, and least for the gapped homoduplex DNA. These differences in DNase I sensitivity can be explained in terms of differences in the accessibility of various strands on the basis of a three-dimensional model for the strand exchange reaction. PMID- 2204619 TI - The structure of protein-protein recognition sites. PMID- 2204620 TI - Pertussis toxin produces differential inhibitory effects on basal, P2-purinergic, and chemotactic peptide-stimulated inositol phospholipid breakdown in HL-60 cells and HL-60 cell membranes. AB - P2-purinergic receptor agonists (UTP) and formylated peptide receptor agonists (FMLP) were found to be equally efficacious in eliciting rapid 6-7-fold increases in inositol polyphosphate accumulation in differentiated HL-60 granulocytes. The activation of this response by either agonist was substantially but incompletely inhibited in cells treated with pertussis toxin. Thus, in cells containing only 1 10% of the control level of non-ADP-ribosylated Gi-2/3, UTP induced rapid 2-fold increases in inositol polyphosphate accumulation whereas smaller 50% increases were observed in FMLP-stimulated cells. Washed membranes prepared from control and toxin-treated HL-60 cells were used to characterize this toxin-insensitive activation of phospholipase C further. The agonist-independent stimulation of phospholipase C by either millimolar Ca2+ or the nonhydrolyzable GTP analog guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) was only modestly attenuated by toxin treatment. There was a 70-80% decrease in the rate and extent of phospholipase C activity stimulated by GTP per se in the absence of receptor agonists. The rate and extent of FMLP-induced potentiation of GTP-dependent phospholipase C activity were also inhibited by greater than 80% in toxin-treated membranes. Conversely, the potency and efficacy characterizing UTP-induced potentiation of GTP-dependent phospholipase C activity were only modestly attenuated (less than 20% inhibition). The results indicate that P2-purinergic receptors (and perhaps other Ca2(+)-mobilizing receptors) activate both pertussis toxin-sensitive and toxin-insensitive pathways for phospholipase C regulation in phagocytic leukocytes. PMID- 2204621 TI - Isolation of a temperature-sensitive mutant with an altered tRNA nucleotidyltransferase and cloning of the gene encoding tRNA nucleotidyltransferase in the yeast Saccharomyces cerevisiae. AB - We have isolated a yeast mutant, ts352, that is temperature-sensitive for growth. The mutation has a general effect on mRNA metabolism and a specific effect on tRNA biosynthesis. Cells shifted to the nonpermissive temperature accumulate tRNAs that are shorter than mature tRNAs. The increased ability of these tRNAs to accept ATP demonstrates that growth of the ts352 mutant at the nonpermissive temperature results in accumulation of tRNA with defective 3' ends. The activity of ATP (CTP):tRNA-specific tRNA nucleotidyltransferase can readily be measured in extracts from wild type but not mutant cells. We have cloned and sequenced the wild type allele of the ts352 gene and find significant similarity between the yeast protein sequence predicted from the DNA sequence and the protein predicted from the sequence of the Escherichi coli tRNA nucleotidyltransferase gene. Expression of the yeast gene on a multicopy plasmid increases the activity of the tRNA nucleotidyltransferase in extracts. We conclude that the defect in the ts352 mutant is in the gene coding for yeast tRNA nucleotidyltransferase and that we have isolated the yeast gene that codes for this enzyme. PMID- 2204622 TI - In vivo portal-hepatic venous gradients of glycogenic precursors and incorporation of D-[3-3H]glucose into liver glycogen in the awake rat. AB - Male Wistar fed rats were chronically cannulated and fed ground chow for 2 h for 6 days. On the 7th post-operative day, blood was simultaneously drawn from the portal and hepatic veins over a 2-h feeding period. The position of the hepatic vein cannula was verified using a tritiated water washout technique. In separate experiments, 200 microCi of [3-3H]glucose was added to the food in order to determine the relative contribution of D-glucose and 3-C precursors to newly synthesized glycogen. The 22-h fasting plasma portal vein concentrations of D glucose, L-lactate, and L-alanine were 4.8 +/- 0.03, 0.81 +/- 0.06, and 0.20 +/- 0.03 mM, respectively (n = 5). The fasting hepatic vein plasma concentrations were 5.1 +/- 0.2, 0.70 +/- 0.15 and 0.19 +/- 0.03 mM, respectively. The portal hepatic vein gradients after 22 h were -0.24, +0.16, and +0.01 mM for D-glucose, L-lactate, and L-alanine, respectively. At 20 min after beginning the meal, the respective gradients were +2.2, +0.53, and +0.44 mM, indicating hepatic uptake of all glycogen precursors. Of the total carbon from the three major precursors entering the liver as C-6, D-glucose contributed 82%, while alanine and lactate contributed 18% at 20 min. As portal vein D-glucose and L-alanine levels exceeded 6.65 +/- 0.69 and 0.32 +/- 0.07 mM, respectively, the portal-hepatic venous gradient became positive and increased linearly with portal concentrations. The glycogen concentration in the liver increased from a 22-h fast value of 5 mumol of glucosyl units/g wet weight to 101 +/- 7 mumol/g 2 h after the meal. The mean specific activity of portal vein plasma of [3-3H]glucose was 11,490 +/- 1,180 dpm/mumol (+/- S.E.) and that in the glycogen isolated from liver was 8,175 +/- 785 dpm/mumol of glycosyl units 2 h after the meal. The specific activity of liver [3H]glycogen relative to glucose after the meal was 0.73 +/- 0.08. It was concluded that a minimum of 73% of the newly synthesized glycogen was formed from the uptake and direct phosphorylation of portal blood D-glucose by the liver without prior conversion of glucose to 3-C units. PMID- 2204623 TI - Receptor-mediated internalization of insulin requires a 12-amino acid sequence in the juxtamembrane region of the insulin receptor beta-subunit. AB - The juxtamembrane region of the insulin receptor (IR) beta-subunit contains an unphosphorylated tyrosyl residue (Tyr960) that is essential for insulin stimulated tyrosyl phosphorylation of some endogenous substrates and certain biological responses (White, M.F., Livingston, J.N., Backer, J.M., Lauris, V., Dull, T.J., Ullrich, A., and Kahn, C.R. (1988) Cell 54, 641-649). Tyrosyl residues in the juxtamembrane region of some plasma membrane receptors have been shown to be required for their internalization. In addition, a juxtamembrane tyrosine in the context of the sequence NPXY [corrected] is required for the coated pit-mediated internalization of the low density lipoprotein receptor. To examine the role of the juxtamembrane region of the insulin receptor during receptor-mediated endocytosis, we have studied the internalization of insulin by Chinese hamster ovary (CHO) cells expressing two mutant receptors: IRF960, in which Tyr960 has been substituted with phenylalanine, and IR delta 960, in which 12 amino acids (Ala954-Asp965), including the putative consensus sequence NPXY [corrected], were deleted. Although the in vivo autophosphorylation of IRF960 and IR delta 960 was similar to wild type, neither mutant could phosphorylate the endogenous substrate pp185. CHO/IRF960 cells internalized insulin normally whereas the intracellular accumulation of insulin by CHO/IR delta 960 cells was 20-30% of wild-type. However, insulin internalization in the CHO/IR delta 960 cells was consistently more rapid than that occurring in CHO cells expressing kinase-deficient receptors (CHO/IRA1018). The degradation of insulin was equally impaired in CHO/IR delta 960 and CHO/IRA1018 cells. These data show that the juxtamembrane region of the insulin receptor contains residues essential for insulin-stimulated internalization and suggest that the sequence NPXY [corrected] may play a general role in directing the internalization of cell surface receptors. PMID- 2204624 TI - Mapping the active site of yeast RNA polymerase B (II). AB - Yeast RNA polymerase B (II) was incubated with a collection of 13 different nucleotide derivatives and affinity labeled by allowing DNA-directed phosphodiester bond formation. The 32P-labeled site was localized in the C terminal part of the B150 subunit by microsequencing a proteolytic fragment, then further mapped by a combination of extensive or single-hit chemical cleavage reactions and analysis of the labeled peptide patterns. The affinity label was mapped to between Asn946 and Met999, within one of the nine regions that are conserved between B150 and the bacterial beta subunit. The results underscore the conservative evolution of the catalytic center of eukaryotic and bacterial RNA polymerases. PMID- 2204625 TI - Rapid insulin-stimulated accumulation of an mRNA encoding a proline-rich protein. AB - By differential hybridization screening of a cDNA library derived from insulin stimulated cells, we selected a clone which hybridized to an mRNA species that rapidly accumulated in response to insulin. The insert from this clone encoded a putative polypeptide of Mr 33,600, pI 11.2; because the protein was enriched in proline residues (14.4 mol %) and contained three Pro-Pro-Pro-Pro repeats, we have tentatively labeled it tris-tetraprolin (TTP). The function of this protein is not known, but it contains two regions very rich in proline (30-40 mol %); similar proline-rich regions have been shown to be involved in transcriptional activation by other proteins. The mRNA (2.0 kilobases) encoding the TTP protein was essentially undetectable in serum-deprived HIR 3.5 cells, but accumulated dramatically within 10 min of stimulation by insulin. This effect appeared to be due to insulin acting through the intrinsic protein-tyrosine kinase activity of its own receptor. Insulin induction of TTP mRNA accumulation was prevented by actinomycin D and superinduced by cycloheximide. Accumulation of TTP mRNA was also stimulated by a variety of growth factors and active phorbol esters; however, the insulin effect was virtually normal in cells depleted of protein kinase C. A single TTP gene appeared to be present in the mouse genome. This gene joins the group of genes whose members are rapidly transcribed in response to insulin and other mitogens. PMID- 2204626 TI - Nucleotide sequence, expression, and properties of luciferase coded by lux genes from a terrestrial bacterium. AB - The lux genes required for expression of luminescence have been cloned from a terrestrial bacterium, Xenorhabdus luminescens, and the nucleotide sequences of the luxA and luxB genes coding for the alpha and beta subunits of luciferase determined. The lux gene organization was closely related to that of marine bacteria from the Vibrio genus with the luxD gene being located immediately upstream and the luxE downstream of the luciferase genes, luxAB. A high degree of homology (85% identity) was found between the amino acid sequences of the alpha subunits of X. luminescens luciferase and the luciferase from a marine bacterium, Vibrio harveyi, whereas the beta subunits of the two luciferases had only 60% identity in amino acid sequence. The similarity in the sequences of the alpha subunits of the two luciferases was also reflected in the substrate specificities and turnover rates with different fatty aldehydes supporting the proposal that the alpha subunit almost exclusively controls these properties. The luciferase from X. luminescens was shown to have a remarkably high thermal stability being stable at 45 degrees C (t 1/2 greater than 3 h) whereas V. harveyi luciferase was rapidly inactivated at this temperature (t 1/2 = 5 min). These results indicate that the X. luminescens lux system may be the bacterial bioluminescent system of choice for application in coupled luminescent assays and expression of lux genes in eukaryotic systems at higher temperatures. PMID- 2204627 TI - A Pro to Gly mutation in the hinge of the arabinose-binding protein enhances binding and alters specificity. Sugar-binding and crystallographic studies. AB - The L-arabinose-binding protein (ABP) of Escherichia coli consists structurally of two distinct globular domains connected by a hinge of three separate peptide segments. Arabinose is bound and completely sequestered within the deep cleft between the two domains. With reduced affinity, ABP also binds D-galactose (approximately 2-fold reduction) and D-fucose (approximately 40-fold reduction). Experiments have been conducted to explore the role in sugar binding of the hinge connecting the two domains of ABP. To increase the flexibility of the hinge region, a glycine was substituted for a proline at position 254 by site-directed mutagenesis. Unexpectedly, this mutation resulted in the dramatic enhancement of galactose binding over that of arabinose. The affinity of the mutant ABP for galactose increased by over 20-fold, while that for arabinose and fucose remained relatively unchanged. We have measured association and dissociation rates of the Gly-254 ABP with L-arabinose, D-galactose, and D-fucose and have determined the crystallographic structure of the protein complexed with each of the three sugars. Both the ligand-binding kinetic measurements and structure analysis indicate that the altered specificity is due to an effective increase in the rigidity of the hinge in the closed conformation which is induced upon galactose binding. Stabilizing contacts are formed between the strands of the hinge in the Gly-254 ABP when galactose is bound which are not found in complexes with the other sugars or the liganded wild-type protein. PMID- 2204629 TI - Ribosomal proteins L15 and L16 are mere late assembly proteins of the large ribosomal subunit. Analysis of an Escherichia coli mutant lacking L15. AB - The (minus L15) character from the Escherichia coli strain AM16.98 was transduced to an RNase-deficient strain in order to enable a reconstitution analysis. The following results were obtained. 1) The strain lacking L15 showed a 2-3-fold prolonged generation time and the 70 S ribosomes a reduced tendency toward dissociation. 2) Active particles could not be reconstituted unless L15 was added. Addition of L15 regained activity, even if L15 was added after the two step procedure during a third incubation. However, a modification of the standard two-step reconstitution procedure (lowering NH4+ from 400 to 240 mM and the incubation temperature of the second step from 50 to 47 degrees C) yielded 100% active particles in the absence of L15. Active particles could be formed which even lacked L15, L16, and L30. Addition of either L15 or L16 accelerated the formation of active particles in the second step by a factor of five, and both proteins together by a factor of more than 20. 3) The activation energy of the rate-limiting step of the second incubation was surprisingly reduced for about 20 kcal/mol in the absence of L15, although the corresponding rates were two to five times slower. We conclude 1) that L15 and L16 are late assembly proteins which accelerate the formation of active particles during the late assembly but are neither needed for the early assembly nor essential for ribosomal functions; 2) that some routes of the late assembly (e.g. incorporation of L16) are changing their significance depending on the NH4+ concentration and the absence and presence of L15; and 3) that different reactions are rate limiting during the second step incubation in the presence and absence of L15, respectively, and that the corresponding reaction rates exhibit a different temperature dependence. PMID- 2204628 TI - Secretion of functional papain precursor from insect cells. Requirement for N glycosylation of the pro-region. AB - The synthetic gene coding for the precursor of the cysteine protease papain (EC 3.4.22.2) has been expressed using the baculovirus/insect cell system. The prepropapain gene was cloned into the transfer vector IpDC125 behind the polyhedrin promoter. The recombinant construct was then incorporated by homologous recombination into the Autographa californiaca nuclear polyhedrosis virus genome. The host Spodoptera frugiperda Sf9 cells infected with the recombinant baculovirus secrete an enzymatically inactive N-glycosylated papain precursor. This zymogen could be activated in vitro to yield about 400 nmol of active papain per liter of culture. The recombinant active mature papain was enzymatically indistinguishable from natural papain but the precursor was not processed to the same amino acid residue. The insect cells also accumulated prepropapain and glycosylated propapain intracellularly. This accumulation was an indication that there are rate-limiting steps in the secretion of proteins from insect cells in this expression system. Characterization of mutants of the precursor has shown that entry into the secretory pathway and addition of carbohydrate are prerequisite conditions for the production and secretion of functional propapain. PMID- 2204630 TI - Glenohumeral osteoarthrosis. A late complication of the Putti-Platt repair. AB - Osteoarthrosis of the glenohumeral joint is a potential late complication of anterior Putti-Platt capsulorrhaphy. In ten patients (eleven shoulders), disabling pain in the shoulder began an average of 13.2 years after a Putti-Platt repair that had been done for recurrent anterior unidirectional instability. In all of the patients, the osteoarthrosis of the glenohumeral joint resulted in substantial limitation of motion. Seven shoulders were successfully treated non operatively, and a technique of anterior release was successful in four shoulders. PMID- 2204631 TI - Operative treatment of palsy of the posterior interosseous nerve of the forearm. AB - The cases of forty patients who were operated on consecutively for palsy of the posterior interosseous nerve were analyzed. The injury was iatrogenic in sixteen patients, traumatic in fifteen, and nontraumatic in nine. Persistent paralysis (partial or complete) was the only indication for operation. Operative neurolysis was done in twenty-three patients; interfascicular nerve-grafting, in twelve; internal neurolysis, in one; and tendon transfer, in four. An excellent or good functional result was documented for all but three patients, of whom two had had neurolysis and one, nerve-grafting. PMID- 2204632 TI - Acetabular reconstruction with a bipolar prosthesis and morseled bone grafts. AB - The results of eighteen acetabular reconstructions in which a bipolar prosthesis and morseled bone grafts were used for a major acetabular defect were evaluated. Thirteen Type-II (cavitary) and five Type-III (combined) acetabular deficits were treated. All of the patients were followed for at least two years. The procedure failed in eleven patients: six had radiographic evidence of complete resorption of the bone grafts and migration of the acetabular component; three, deep infection; one, recurrent dislocation; and one, pain of undetermined cause despite a satisfactory radiographic appearance of the hip. The remaining seven patients had a satisfactory clinical outcome. However, an improved acetabular bone structure, as judged by radiographic evidence of incorporation of the bone grafts, was maintained in only four patients. In our experience, acetabular reconstruction with morseled bone grafts and a bipolar prosthesis was associated with a high rate of failure, and we do not recommend that it be performed routinely. It should be considered only as a salvage procedure in elderly or infirm patients, as a possible alternative to more extensive procedures. PMID- 2204633 TI - Salvage of total knee arthroplasty with local fasciocutaneous flaps. AB - Six patients who had delayed healing of the wound after total knee replacement were treated by appropriate debridement and restoration of soft-tissue coverage with local fasciocutaneous flaps. This procedure was successful; deep infection and failure of the arthroplasty did not develop in any patient. PMID- 2204634 TI - Migration of pins used in operations on the shoulder. PMID- 2204635 TI - Current interests in child-adult psychopathological continuities. PMID- 2204636 TI - Effect of root debridement on the elimination of Actinobacillus actinomycetemcomitans and Bacteroides gingivalis from periodontal pockets. AB - The aims of this 6-month longitudinal study were: (1) to investigate to what extent root debridement of pockets in adult periodontitis will reduce the subgingival presence of Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and some other bacterial groups; (2) to relate the microbiological results following debridement to clinical measurements of healing. 16 patients and a total of 111 periodontally involved sites with probing depth greater than or equal to 6 mm served for the study. Duplicate subgingival microbial samples and duplicate clinical recordings were obtained 1 week apart at baseline and at 6 months following supra- and subgingival debridement. The results demonstrated reductions of the mean total viable counts and reductions of the mean counts of several of the cultured groups of micro-organisms coupled with significant improvements of mean clinical measurements. B. gingivalis was eliminated from a majority of infected subgingival sites. A. actinomycetemcomitans, on the other hand, still remained after therapy in a high proportion of sites initially infected with this microorganism. Subgingival persistence of A. actinomycetemcomitans appeared to be associated with a reduced healing response following debridement. Further studies are needed to clarify why A. actinomycetemcomitans is poorly eliminated following debridement. Also, the long term clinical significance of the subgingival perseverance of A. actinomycetemcomitans needs to be elucidated. PMID- 2204637 TI - Thoracic collateral venous channels: normal and pathologic CT findings. AB - Opacification of thoracic collateral venous channels (CVC) on chest CT is considered a useful sign of superior vena cava (SVC) obstruction, although its lack of specificity has occasionally been emphasized. We compared the degree of opacification of six various thoracic CVC in a group of 36 patients with SVC syndrome and in a control group of 50 patients; a dynamic incremental CT technique with bolus injection was used. Opacification of at least one CVC is inaccurate for the diagnosis of SVC obstruction, with a false-positive and false negative rate of 34 and 31%, respectively. Only the opacification of the subcutaneous anterior channel provides a good specificity (96%), significantly higher (p less than 0.05) than that observed for the posterior collateral channels. In patients in whom the clinical records and other direct CT signs of vena cava obstruction are doubtful or absent, opacification of a subcutaneous anterior channel on chest CT should lead to a suspicion of obstruction of the SVC and cavography should be performed. PMID- 2204638 TI - MR imaging of neurilemoma arising from the renal hilus. AB - The authors present the radiologic findings of a neurilemoma arising from the kidney. Ultrasound, CT, and angiography could not exclude the diagnosis of renal cell carcinoma (RCC). Magnetic resonance (MR) imaging at 1.5 T showed an isointense tumor on T1-weighted images and a high signal intensity on T2-weighted images compared with normal renal parenchyma. The MR findings were helpful in the differentiation from RCC. PMID- 2204639 TI - Hydrocephalus and porencephaly: prenatal diagnosis by ultrasonography and MR imaging. PMID- 2204640 TI - Stereotactic retrobulbar anesthesia using CT. AB - A simple technique using stereotactic needle placement for retrobulbar anesthesia is reported. The method utilizes a CT-guided stereotactic device that permits precise intraconal injection of local anesthetics; in addition, the risk of injury to muscles, vessels, eyeglobe, or optic nerve is substantially reduced. PMID- 2204641 TI - The RNA polymerases of Porphyromonas gingivalis and Fusobacterium nucleatum are unrelated to the RNA polymerase of Escherichia coli. AB - Western blot analysis that used antisera to the E. coli core enzyme and sigma factors was used for examination of the RNA polymerase of Actinobacillus actinomycetemcomitans, Streptococcus mutans, Fusobacterium nucleatum, and Porphyromonas gingivalis. Both antisera reacted with proteins in A. actinomycetemcomitans and S. mutans whole-cell extracts. Reactions were seen with some F. nucleatum proteins when the anti-core RNA polymerase antisera were used, but the cross-reacting proteins were not of an expected molecular weight for beta or beta'. No reaction with F. nucleatum proteins was seen when extracts were reacted with antisera to E. coli sigma factor. There were no cross-reacting proteins detected in P. gingivalis extracts with either antisera. These results suggest that E. coli RNA polymerase may not be sufficiently similar to P. gingivalis and F. nucleatum RNA polymerase for E. coli RNA polymerase to recognize P. gingivalis or F. nucleatum promoters. Partially purified P. gingivalis and F. nucleatum RNA polymerase exhibited a specificity for a P. gingivalis DNA template, while having a decreased activity from an E. coli DNA template. The antibiotic sensitivity profile of P. gingivalis and F. nucleatum RNA polymerase activity was shown to differ from that of E. coli, with these activities not being affected by rifampicin, streptovaricin, or streptolydigin. We conclude that the efficient cloning and expression of P. gingivalis and F. nucleatum genes in E. coli will require the use of promoter-containing expression vectors. PMID- 2204642 TI - Preliminary surface analysis of etched, bleached, and normal bovine enamel. AB - X-ray photoelectron spectroscopic (XPS) and secondary ion-mass spectroscopic (SIMS) analyses were performed on unground un-pumiced, unground pumiced, and ground labial enamel surfaces of young bovine incisors exposed to four different treatments: (1) immersion in 35% H2O2 for 60 min; (2) immersion in 37% H3PO4 for 60 s; (3) immersion in 35% H2O2 for 60 min, in distilled water for two min, and in 37% H3PO4 for 60 s; (4) immersion in 37% H3PO4 for 60 s, in distilled water for two min, and in 35% H2O2 for 60 min. Untreated unground un-pumiced, unground pumiced, and ground enamel surfaces, as well as synthetic hydroxyapatite surfaces, served as controls for intra-tooth evaluations of the effects of different treatments. The analyses indicated that exposure to 35% H2O2 alone, besides increasing the nitrogen content, produced no other significant change in the elemental composition of any of the enamel surfaces investigated. Exposure to 37% H3PO4, however, produced a marked decrease in calcium (Ca) and phosphorus (P) concentrations and an increase in carbon (C) and nitrogen (N) concentrations in unground un-pumiced specimens only, and a decrease in C concentration in ground specimens. These results suggest that the reported decrease in the adhesive bond strength of resin to 35% H2O2-treated enamel is not caused by a change in the elemental composition of treated enamel surfaces. They also suggest that an organic-rich layer, unaffected by acid-etching, may be present on the unground un pumiced surface of young bovine incisors. This layer can be removed by thorough pumicing or by grinding. An awareness of its presence is important when young bovine teeth are used in a model system for evaluation of resin adhesiveness. PMID- 2204644 TI - Mapping our way through the information jungle. PMID- 2204643 TI - Adhesive bonding of titanium with a titanate coupler and 4-META/MMA-TBB opaque resin. AB - Adhesive bonding of titanium was evaluated with a titanate primer and adhesive opaque resin. The primer consisted of 2% isopropyl dimethacryloyl isostearoyl titanate in methyl methacrylate. The adhesive was 4-META/MMA-TBB opaque resin that contained 4-methacryloyloxyethyl trimellitate anhydride and was initiated by tri-n-butylborane derivative. Titanium discs were machined and blasted with aluminum oxide. They were primed and bonded together with the opaque resin. A shear test was performed after repeated thermocycles for investigation of the durability of the bond. The shear strength of the primed and 4-META resin-bonded specimens was 37.2 MPa after 50,000 thermocycles, with only a small decrease in bond strength. This was significantly higher than the control values. Thus, titanate primer and 4-META/MMA-TBB opaque resin may be used for the bonding of titanium in prosthodontic practice. PMID- 2204645 TI - Catching information technology by the tail for problem-based learning. AB - While computer-based resources are appealing, there is currently little evidence that they are superior to less expensive, traditional educational technologies and thus their introduction will be slow until we learn how to benefit from them. The lesson learned from the orientation of problem-based learning is that communications aspects of the new technologies may be much more important and should be, at least currently, the focus of attention. Thus, rather than concerning ourselves with the tiger, since communications do not require particularly sophisticated equipment, the important approaches now appear to be to give students experience with the means to access and exchange information; with those skills they should be reasonably prepared to survive in the Information Age and take advantage of what technology has to offer in the future. PMID- 2204647 TI - The literature of dermatologic surgery and oncology 1970-present. PMID- 2204646 TI - Presuturing in alopecia reductions. AB - The technique of presuturing for alopecia reductions is described. With this procedure, the area of potential reduction is sutured 12-24 hours prior to surgery to enhance the laxity of the scalp. PMID- 2204649 TI - President's page: the Midas touch. PMID- 2204648 TI - Nutritional effects of marijuana, heroin, cocaine, and nicotine. AB - Use of addictive drugs, such as cocaine, marijuana, and nicotine, affects food and liquid intake behavior, taste preference, and body weight. Changes in specific nutrient status and metabolism can also develop; heroin addiction can cause hyperkalemia and morphine use can result in calcium inhibition. Nutrition related physiological aspects, such as impaired gastrin release, hypercholesterolemia, hypothermia, and hyperthermia, are also seen with morphine use. Nutrition-related conditions can affect sensitivity to and dependence on drugs and their effects. Diabetes decreases sensitivity to and dependence on morphine, protein deprivation produces preferential fat utilization with low cocaine use, and vitamin D deficiency decelerates morphine dependency. During use and/or withdrawal from nicotine, heroin, marijuana, and cocaine, major changes in food selection and intake occur, which result in weight gain or loss. Detailed human studies are needed to investigate the effects of drug use on the broad spectrum of nutrients and to determine the role of nutrition during drug withdrawal. PMID- 2204650 TI - Spasticity in cerebral palsy and the selective posterior rhizotomy procedure. AB - A review of the selective posterior rhizotomy procedure for reduction of spasticity in cerebral palsy is presented. The history of the procedure, selection of patients, operative technique, and results are described. The neurophysiologic basis for spasticity is considered, as well as the role of spasticity in the complex motor disorder of cerebral palsy. Cerebral palsy is a multifaceted disorder of which spasticity is only one aspect. Reduction of spasticity can be effectively achieved using the current technique of selective posterior rhizotomy, but careful patient selection and establishment of realistic goals are vital to successful outcome. Postoperative physical and occupational therapy are felt to be essential for regaining strength and improving motor function following the rhizotomy procedure. Further study in the areas of spasticity, cerebral palsy, and the effects of rhizotomy is expected to advance our treatment of spastic children. PMID- 2204651 TI - Randomized clinical trial of two colonoscopy preparation methods for elderly patients. AB - Colonic lavage with enemas or with Golytely are standard preparation methods for colonoscopy. Previous studies have demonstrated that Golytely has a statistically significant advantage in both adequacy of preparation and patient tolerance. To determine if these effects are present in the elderly, we performed a randomized clinical trial on 124 consecutive patients scheduled for colonoscopy who were greater than or equal to 75 years of age. Sixty-three patients were randomized to receive Golytely; 17 were inpatients, 33 were outpatients, and colonoscopy was canceled in 13. Sixty-one patients were randomized to receive the enema preparation; 17 were inpatients, 30 were outpatients, and colonoscopy was canceled in 14. For adequacy of the preparation, no differences were statistically significant, but the enema preparation was superior in outpatients while Golytely was superior in inpatients. Patients tolerated the enema preparation better, a finding present in both outpatients and inpatients. Contrary to previous reports of a significant advantage with Golytely, patients greater than or equal to 75 years old did not enjoy this advantage, but seemed to tolerate enemas better than Golytely with little difference in adequacy of the preparation. PMID- 2204653 TI - Spontaneous Salmonella infection of high-protein noncirrhotic ascites. AB - Spontaneous bacterial peritonitis rarely complicates high-protein (greater than 2.5 g/dl) ascites. The relatively high endogenous antimicrobial (opsonic) activity of the ascitic fluid in this setting appears to protect the patient from infection. We report two patients with high-protein, noncirrhotic ascites complicated by spontaneous peritonitis due to Salmonella species. One patient had ascites due to heart failure, whereas the other patient's ascites was due to peritoneal carcinomatosis. The ascitic fluid total protein concentrations were 3.1 and 3.3 g/dl, respectively, and the opsonic activity of the ascitic fluid specimens were 2.03 and 2.00 log kill, respectively, indicating a high degree of bacterial killing. We hypothesize that the virulence of the Salmonella species was able to overcome the high opsonic activity in the ascitic fluid, resulting in infection in these two patients. Fever, abdominal pain, or encephalopathy in a patient with high-protein ascites may suggest the presence of an unusual organism causing spontaneous bacterial peritonitis. PMID- 2204652 TI - Pancreatic abscess due to mycobacterial infection associated with the acquired immunodeficiency syndrome. AB - Two patients with a history of intravenous drug abuse developed a pancreatic abscess due to mycobacterial infection as their initial evident opportunistic infection in association with the acquired immunodeficiency syndrome (AIDS). This presentation of mycobacterial infection has been previously reported in nine patients. The two patients reported here are the second and third reported cases in association with AIDS. As this entity should be considered a cause of a pancreatic lesion in immunosuppressed patients, fluid drained from a pancreatic abscess should have histologic stains and cultures for mycobacteria. PMID- 2204654 TI - Pseudotumor appearance in chronic hepatitis. AB - A pseudotumor appearance of the liver has not been previously described in chronic hepatitis. We reviewed 81 charts with a biopsy diagnosis of "chronic hepatitis" and at least one radiologic liver scan, and found four cases with a pseudotumor appearance. They all had features on radiologic scans suggestive of space-occupying lesions. Histology showed chronic hepatitis in all four. Two were cirrhotic, one due to alcohol and the other due to hepatitis B. The other two patients had chronic active hepatitis with regenerative nodules but only limited fibrosis, one due to hepatitis B, the other probable non-A, non-B. None had any evidence of hepatic malignancy. We conclude that some patients with chronic hepatitis may present with a pseudotumor appearance on radiological scans, due to the presence of regenerative nodules. Space-occupying lesions on liver scans in chronic hepatitis may represent non-neoplastic liver disease. PMID- 2204655 TI - Primary and secondary malignant disease of the liver and fulminant hepatic failure. AB - The association and presentation of malignant disease of the liver with fulminant hepatic failure has been described sporadically, but the absence of a large series has meant that malignancy is rarely considered in the differential diagnosis of such hepatic failure. We describe three cases and review the best documented reports in the literature. Review of 25 patients shows that in most cases, excluding lymphoma, the liver is massively replaced by tumor that often spreads in an intrasinusoidal pattern. The diffuse nature of malignant spread results in a relative failure of diagnostic imaging and thus the diagnosis is frequently made after death, which occurs a mean 7.8 days after hospital admission. Review of the clinical features and investigations in these cases shows that, when hepatomegaly and ascites are present in middle-aged or older patients at the time of admission, malignancy should be considered as the cause. Why the liver should be massively replaced in such patients remains obscure. PMID- 2204656 TI - Intramural pancreatic pseudocyst in the gastric wall: diagnosis by sonography and ultrasound-guided puncture. AB - We report a patient with recurrent chronic pancreatitis who developed a pancreato gastric fistula. Maturation of a pseudocyst within the gastric wall was followed by sonography, and diagnosis was established by ultrasound-guided puncture. PMID- 2204657 TI - Is HLA matching important for liver transplantation? PMID- 2204658 TI - Polymerase chain reaction. A new tool for the study of viral infections in hepatology. PMID- 2204659 TI - Ursodeoxycholic acid treatment for chronic cholestatic liver disease. PMID- 2204660 TI - Major histocompatibility complex antigens in human liver transplants. AB - Liver transplantation is performed successfully across major HLA differences between donor and recipient. This may be influenced by the organ specific expression of major histocompatibility complex (MHC) molecules which determine the local immune reactivity and rejection response. The tissue expression of MHC molecules on parenchymal and infiltrating cells has been studied in transplanted human liver using monoclonal antibodies and immunohistological methods. A strong induction of class I (HLA-A,B,C; beta 2-microglobulin) and class II (HLA DR,DQ,DP) MHC antigens was demonstrated on hepatocytes, bile duct epithelium and endothelial cells during rejection episodes and viral and bacterial infections. The massive induction of donor antigens on hepatocytes, bile ducts and endothelia forms part of, and may also augment, the rejection response. During quiescent states without infection or rejection after transplantation, however, a rather restricted expression of class I and class II donor MHC antigens is present. In addition, the donor Kupffer cells and interstitial dendritic cells are gradually replaced by recipient accessory cells expressing self-MHC molecules. The changes in antigen density and distribution of donor MHC alloantigens as the replacement of accessory cells capable of presenting antigens to T-lymphocytes may influence the course of immune reactivity and the rejection response in the liver. This may partly explain the favourable clinical course long after transplantation. Preliminary clinical investigations of the effect of HLA matching have shown a dualistic effect of the matching of class I or class II HLA antigens. The role of HLA matching in liver transplants in large clinical studies, with specific immunological testing however, remains to be investigated. This may lead to prospective HLA matching with wider organ availability and improved preservation time in the future.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2204661 TI - Long-term oral branched-chain amino acid treatment in chronic hepatic encephalopathy. A randomized double-blind casein-controlled trial. The Italian Multicenter Study Group. AB - In a double blind randomized study, branched-chain amino acids and placebo (casein) were compared as a treatment for chronic hepatic encephalopathy in cirrhosis. After a 15-day run-in period with controlled diet (45-65 g protein), the patients were administered, in addition to their diet, branched-chain amino acids (0.24 g/kg, 30 patients) or an equinitrogenous amount of casein (34 patients). One patient on branched-chain amino acids and two on casein were lost to the study. After 3 months, the index of portal-systemic encephalopathy significantly improved in patients on active treatment (from 40 [S.D. 14]% to 21 [17]), but was not in subjects receiving casein (from 37 [13]% to 36 [12]). Two or more parameters of the index improved in 24 patients treated with amino acids (80%; confidence limits, 61-92%), and only in 12 receiving casein (35%; confidence limits, 20-54%; p less than 0.001). Patients who did not improve were given an alternative treatment for 3 more months. Casein-treated patients given branched-chain amino acids rapidly improved. The changes in neuropsychologic function were associated with an improvement in semiquantitative nitrogen balance, which became consistently positive in amino acid-treated subjects; there was also a mild improvement in nutritional parameters and in liver function tests. The supplementation of oral branched-chain amino acids to the diet is superior to casein as a treatment for providing adequate nitrogen supply and improving the mental state of cirrhotic patients with chronic encephalopathy. PMID- 2204662 TI - A critical appraisal of studies of the pancreas. Animal models used in pancreas research: studies on feedback regulations of the pancreas. AB - This article suggests that for the concept of feedback regulation of the pancreas the application of animal data to humans has obvious limitations. The introduction of the synthetic protease inhibitor camostate (FOY 305) offered the possibility of designing studies in animals and man using the same compound as tool thus allowing reliable comparisons between the different experiments. These experiments revealed that cholecystokinin (CCK) has a dominant role in rats but it has no proven significance for feedback regulation in humans. The existence of such species differences should be kept in mind in studies dealing with pancreatic secretion, growth, pancreatitis, cancer, or related questions. PMID- 2204663 TI - [Successful mitral valve replacement for infective endocarditis in pregnancy]. AB - A 27 weeks' pregnant women exhibited infective endocarditis due to alpha streptococcus. As echocardiography showed vegetations on both mitral leaflets, cesarean section was performed at 35 weeks' gestation and a healthy male infant weighing 2,430 g was delivered. Antibiotic therapy was continued for fever after the cesarean section but macrohematuria and Osler's nodes developed. Emergency mitral valve replacement was performed successfully despite the presence of active infective endocarditis. She was discharged after completion of a 10-week course of antibiotic therapy. PMID- 2204664 TI - [A case of giant thymolipoma in a child]. AB - A case report of a giant thymolipoma in 6-year-old boy is reported. Following school screening, an abnormal shadow in the left chest was found on the chest X ray. CT scan and MRI suggested the mediastinal tumor containing a fatty mass. The tumor was resected on bloc through the median sternotomy and left antero-lateral thoracotomy. The tumor was 85 X 210 X 140 mm in size and 1380 g in weight. The postoperative histological examination revealed the thymolipoma. We were able to find only 19 other reported cases of thymolipoma in Japanese literature. Of 19 cases, this thymolipoma is the largest one in proportion to the patient's body weight. PMID- 2204665 TI - [Minor strut fracture of the Bjork-Shiley mitral valve]. AB - In May, 1982, a 49-year-old man underwent mitral valve replacement (MVR) in our hospital with a 31 mm Bjork-Shiley prosthesis for mitral regurgitation. He had been doing well until his episode of palpitation and dyspnea of sudden onset, and was transferred to our ICU with severe cardiogenic shock in Aug, 1986. Chest X ray film revealed pulmonary edema and breakage of the valve with migration of the disc and the minor strut of the prosthesis. He was operated upon 5 hours after the onset of his complaints. The minor strut was removed from the left upper pulmonary vein and mitral valve re-replacement was done with a 29 mm Bjork-Shiley Monostrut valve. The disc which had dislocated into the abdominal aorta was also recovered on the twenty-third post operative day. His postoperative course was uneventful. Immediate diagnosis and subsequent re-operation is absolute indication for rescue from acute cardiac failure due to mechanical failure of any prosthetic valve. PMID- 2204666 TI - [A case report of synchronous double cancer of the lung and esophagus]. AB - A 69-year-old man was admitted to our department with complaint of difficult swallowing. Upper gastrointestinal examination showed esophageal cancer and squamous cell carcinoma of the middle thoracic esophagus was revealed histologically. Chest X-ray showed the atelectasis of the B-3 region of right upper lobe of the lung. Further examinations revealed histologically squamous cell carcinoma growing from B-3 bronchus. Finally, he was diagnosed as synchronous double carcinoma of the lung and the esophagus. Simultaneous operation was performed on May 20, 1988. First, right upper lobectomy of the lung and wedged resection of right main bronchus were performed. Esophagectomy and antesternal esophageal reconstruction using the gastric tube was added. The postoperative course was satisfactory without any severe complications. The synchronous double cancer of the lung and the esophagus is rare. Our case indicates that simultaneous resection of both cancer and esophageal reconstruction can be safely performed. PMID- 2204667 TI - [Successful resection and reconstruction of the left atrium, right atrium and atrial septum under extracorporeal circulation in a patient with invasive pulmonary carcinoma]. AB - A 69-year-old man was admitted to our hospital with a complaint of cough and hemoptysis. His chest X-ray showed an obstruction of the right intermediate bronchus and resultant atelectasis of the middle and lower lobes. Cytological examination by bronchoscopy showed squamous cell carcinoma. Although the cancer involvement of the left atrium could not be clearly defined by preoperative chest CT scan, the cancer invasion to the left atrial wall was recognized intraoperatively. Right pneumonectomy along with resection and patch reconstruction of the left atrium, right atrium and atrial septum was performed under extracorporeal circulation. Postoperative hemodynamic state was stable, and echocardiography showed normal volume of the left atrium. Histological examination of the resected specimen showed moderately differentiated squamous cell carcinoma with the involvement of the left and right atrial wall. The resected margins of the left and right atria were free of malignancy. Although he had been clinically in good condition and free from any sign of cancer recurrence, he died of aspiration pneumonia five months after the surgery. PMID- 2204668 TI - [Clinicopathologic assessment of esophageal cysts--a report of 8 cases]. AB - We experienced 8 cases of esophageal cysts on between January, 1965 and March, 1989. During the same period, 320 cases of mediastinal tumors were operated in our department, and esophageal cysts were 2.5% of these cases. They were 7 males and 1 female, and ranged in age from 5 to 51 (mean 29.9) years. The cysts were located in the right in 6 and in the left in 2, and in the upper third of the esophagus in 1, middle third in 3 and lower third in 2 cases. A correct preoperative diagnosis was made in only 1 case. The definite diagnoses were not obtained from thoracic CT scans and esophagography. We tried transesophageal ultrasonic endoscopy in the recent 2 cases, and could diagnosed in 1 case as a cyst in the esophageal wall. The another case, we could not diagnose, was a cyst attached to the esophageal wall by a muscular stalk. We experienced 2 cases of post operative bleedings, so we must be careful of hemostasis of the muscular layers after enucleation of the cysts. Histological examinations of the cysts showed ciliated columnar epithelium in all cases. Cartilage were observed (bronchogenic cysts) in 4 patients (50%) and two muscle layers were observed (duplication cysts) in 4 other patients (50%). But 2 cases of bronchogenic cysts had two muscular layers, 1 case of them was well-defined. And 1 case of duplication cyst had poor two muscular layers. We cannot divide clearly the esophageal cysts into bronchogenic cyst or duplication cyst, in the point of having cartilage and double muscle layers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2204670 TI - Chemotherapy for squamous cell carcinoma of the head and neck: an overview. AB - Chemotherapy is being utilized to treat patients with recurrent tumors and advanced squamous cell carcinoma of the head and neck. Current treatment modalities utilized include intra-arterial chemotherapy, simultaneous and sequential chemotherapy and radiation therapy, and neoadjuvant chemotherapy. Each of these modes of treatment, as well as pharmacology of squamous cell-active chemotherapeutic agents, will be addressed in this review. PMID- 2204669 TI - [The preoperative and postoperative carcinoembryonic antigen test in the diagnosis, staging, and prognosis of gastric cancer. Tumor Marker Committee, Japanese Foundation for Multidisciplinary Treatment of Cancer]. AB - Preoperative and postoperative carcinoembryonic antigen (CEA) levels were studied in 3,532 patients with Surgically treated gastric cancer in 52 institutions from 1980 to 1981. These patients had disease resectable with curative intent and were followed for a minimum of 5 years or until death. Among 2,749 Stage I cases, 33 had recurrence and proved to be histologically stage I. A pair matching case control study between these 33 cases and matched 33 stage I controls without recurrence proved that the preoperative CEA level was relatively higher in cases with recurrence (p = 0.079). In Stage II and III cases, an analysis of variance using a cut off level as a block factor was performed. Among 315 Stage II cases, preoperative CEA levels were significantly higher in cases with recurrence than in cases without recurrence. In 468 Stage III cases, no correlations between preoperative CEA levels and high risks of cancer recurrence were detected. In Stage I and Stage II cases, CEA levels significantly increased at the time of recurrence. In conclusion, preoperative high serum CEA levels might be considered one of the risk factors for recurrence of Stage I and II gastric cancers, and monitoring the postoperative CEA levels might be useful in early detection of recurrence. PMID- 2204671 TI - The physician as educator. PMID- 2204672 TI - Telling the truth about rising health care costs. AB - Bureaucrats, businessmen, and the media continue to blame physicians for the rising cost of medical care in the United States. It's time for somebody to tell the American people the truth. PMID- 2204673 TI - Conservatism versus liberalism in medicine. PMID- 2204674 TI - The plateau in cytotoxic cancer drug discovery. AB - An examination of the history of cytotoxic cancer drugs development suggests that this activity is now on a plateau. It is striking that there have been no new chemotype cytotoxic anticancer drugs discovered in the past twenty years, despite the massive national effort in this area. It has been estimated that only 40 to 50% of patients currently diagnosed as having cancer will have a five year survival of the disease. This survival rate has been climbing at less than five percent per decade. Our conclusion is that a greater effort in biological response modification is warranted if we are to significantly affect the plateau. PMID- 2204675 TI - Cell growth and abrupt doubling of membrane proteins in Escherichia coli during the division cycle. PMID- 2204677 TI - N-terminal amino acid sequence of the novel type IIIb trimethoprim-resistant plasmid-encoded dihydrofolate reductase from Shigella sonnei. AB - The type IIIb dihydrofolate reductase, a novel plasmid-encoded enzyme recently identified in Shigella sonnei, has been shown to have some similar biochemical properties to the type IIIa dihydrofolate reductase which was first identified in New Zealand in 1979. However, the type IIIb enzyme has a Ki for trimethoprim of 0.4 microM, and a pI of 5.35 (as compared to 19 nM and 6.1 for the type IIIa); both these results suggest that it is a different enzyme from the prototype type IIIa. The type IIIb dihydrofolate reductase was purified by methotrexate agarose affinity chromatography, yielding a pure protein as determined by HPLC. Automatic amino acid analysis of the purified enzyme showed it to be distinct from all other known plasmid-encoded dihydrofolate reductases and quite different from the type IIIa enzyme. The purified enzyme was examined by SDS-PAGE, which revealed that the type IIIb dihydrofolate reductase was a monomeric protein of Mr 17,200. PMID- 2204676 TI - Cloning of genes required for amino acid biosynthesis from Leptospira interrogans serovar icterohaemorrhagiae. AB - Leptospira interrogans belongs to a large family of important pathogens, which is part of the order Spirochaetales, a distinct group of eubacteria. In order to obtain a better understanding of the genetic organization of this species, we have constructed a DNA library of the serovar icterohaemorrhagiae, using the Escherichia coli vector pUC13. We have isolated Leptospira DNA fragments containing the genetic information required to complement strains of E. coli with defects in proline and leucine biosynthesis. While a 3.9 kb fragment which complemented proA also complemented proB, a 15 kb fragment complementing leuB could not complement other leu mutations. The L. interrogans origin of the cloned DNA fragments was confirmed by DNA-DNA hybridization. The hydridization was specific to the pathogenic species and was not seen with the saprophytic species L. biflexa. PMID- 2204678 TI - The secreted aspartate proteinase of Candida albicans: physiology of secretion and virulence of a proteinase-deficient mutant. AB - It was established that Candida albicans grew rapidly in a simple medium containing yeast extract (0.2%, w/v) plus glucose (2%, w/v). These cultures were in or near to a state of nitrogen limitation and the concentration of secreted aspartate proteinase increased rapidly (within 3-4 h) on addition of BSA. Synthesis and secretion were apparently controlled both positively (induction by albumin or, more probably, the peptides produced from it) and negatively (repression by NH4Cl). A small intracellular pool of the enzyme was detected during production of the enzyme and this pool decreased with the cessation of synthesis and secretion. A stable mutant, IR24, was isolated which secreted less than 0.3% of the amount of the proteinase exported by the parent strain ATCC 10261. The LD50 values for mutant IR24 and the parent strain administered intravenously to mice were greater than 1.0 x 10(9) and 1.6 x 10(6) c.f.u. kg-1 respectively. PMID- 2204679 TI - Regulation of the Saccharomyces cerevisiae WHI2 gene. AB - WHI2 mRNA levels were followed through the growth cycle in WHI2 mutant and wild type cells of Saccharomyces cerevisiae. Levels were high during the first (glucose) phase of growth, and were reduced sharply during the second (ethanol) phase of growth. Transcript levels of the glycolytic genes PDC1 and PYK1 were also measured; they each showed a pattern similar to that of WHI2, whereas transcript levels of the CDC7 gene remained constant throughout the cycle, showing that a decrease in transcription is not a general feature of genes. These results make it unlikely that the WHI2 product acts as an inhibitor of cell proliferation which is activated upon carbon starvation. No difference was observed between the pattern of expression of mutant and wild-type strains, showing that the mutant phenotype was not the result of a change in regulation at the transcriptional level. PMID- 2204680 TI - The relationship of growth rate and catabolite repression with WHI2 expression and cell size in Saccharomyces cerevisiae. AB - Mixtures of D-glucosamine and glucose were used to slow the growth of wild-type and whi2 mutant strains of Saccharomyces cerevisiae without affecting the level of catabolite repression. The following observations were made. Firstly, mutant cells were found to be partially resistant to the inhibitory effect of glucosamine. Secondly, slow growth induced by glucosamine resulted in cells becoming larger, in direct contrast to the effect of slowing growth by glucose limitation in a chemostat or by carbon source substitution. It is concluded that the level of repression/derepression, rather than absolute growth rate, is responsible for controlling cell size. Thirdly, when WHI2 transcript levels were measured it was found that expression was correlated with growth rate rather than the level of repression. These results are interpreted in terms of a model which envisages that the WHI2 product acts as a negative regulator of catabolite repression. A test of this model is reported: it is shown that mutant cells respired more actively in the presence of glucose and grew more rapidly on glycerol, whereas overexpression of WHI2 from multicopy plasmids prevented growth on glycerol and depressed respiration. PMID- 2204681 TI - Localization of endo-oligopeptidase (EC 3.4.22.19) in the rat nervous tissue. AB - The subcellular and regional distribution of endo-oligopeptidase (EC 3.4.22.19), an enzyme capable of generating enkephalin by single cleavage from enkephalin containing peptides, was determined by an enzymatic assay using metorphamide and by immunochemical techniques in the CNS of the rat. The rat CNS contains a membrane-associated form of endo-oligopeptidase, an enzyme predominantly associated with the soluble fraction of brain homogenates. Subcellular fractionation showed that approximately 17% of the total activity of the enzyme is associated with membrane fractions including synaptosomes. Synaptosomal membranes were prepared from neocortex, striatum, hypothalamus, medulla, spinal cord, and cerebellum. The amount of EC 3.4.22.19 activity solubilized by 3-[( 3 cholamidopropyl]dimethylammonio)-1-propanesulfonate from synaptosomal membranes was similar in neocortex, striatum, and hypothalamus, being three- to 10-fold greater than in spinal cord, cerebellum, and medulla. A polyclonal antibody exhibiting high affinity for endo-oligopeptidase was raised in rabbits against the purified rat brain enzyme and used to localize endo-oligopeptidase by Western blotting and by immunoperoxidase techniques. A strong band corresponding to the Mr of EC 3.4.22.19 was found in solubilized proteins obtained from synaptosomal membranes prepared from hypothalamus, neocortex, and striatum when subjected to Western blotting. The immunohistochemical localization of endo-oligopeptidase indicated that the immunoreactivity was confined to gray matter in regions known to be rich in peptide-containing neurons such as the striatum. In the cerebellum, a region poor in peptides, no staining could be detected. The nonuniform distribution of endo-oligopeptidase in rat brain suggests a role in neurotransmitter processing in the CNS. PMID- 2204682 TI - Immunohistochemical detection of phenol sulfotransferase-containing neurons in human brain. AB - Using antibodies raised against human platelet phenol sulfotransferase (PST), immunohistochemical studies were performed to determine the cellular localization of PST in several areas of human brain. In the hippocampus PST immunoreactivity was localized in both the pyramidal and nonpyramidal neurons and was in greatest abundance in the CA2 and CA3 areas. In the striatum the immunoreactivity was most predominant in the large neurons of the globus pallidus and in the medulla the staining was scattered throughout the neurons of the raphe nucleus and the reticular formation. The selective presence of PST in the neurons of the CNS raises the issue as to the role of this enzyme in sulfating neurotransmitters because PST has been shown to be capable of conjugating a variety of neurotransmitters including the catecholamines as well as the tyrosine moiety of a number of small peptides such as enkephalin and cholecystokinin. PMID- 2204683 TI - Effects of N-methyl-D-aspartate on [Ca2+]i and the energy state in the brain by 19F- and 31P-nuclear magnetic resonance spectroscopy. AB - The effects of N-methyl-D-aspartate (NMDA) on the free intracellular Ca2+ concentration [( Ca2+]i) and the energy state in superfused cerebral cortical slices have been studied using 19F- and 31P-nuclear magnetic resonance spectroscopy. [Ca2+]i was measured using the calcium indicator 1,2-bis(2-amino-5 fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid (5FBAPTA). NMDA (10 microM) in the absence of extracellular Mg2+ caused the expected rise in [Ca2+]i but produced an impairment of the energy state: the phosphocreatine (PCr) content was decreased by 42%, and the Pi/PCr ratio was increased by 55%. There was no detectable change in ATP or free intracellular Mg2+ concentration. Increasing the NMDA concentration in the superfusing medium to 100 or 400 microM caused no further increase in [Ca2+]i or further decrease in PCr content, but the Pi/PCr ratio continued to rise. The impairment of the energy state preceded the effect on [Ca2+]i, and these changes were irreversible on return to control conditions. Repeating the experiments in the presence of 1.2 mM extracellular Mg2+ resulted in similar changes in the energy state, with no change in [Ca2+]i. The possibilities that the effects were due to membrane depolarisation or to the presence of 5FBAPTA within the tissues were eliminated. The results suggest that low concentrations (10 microM) of NMDA produce an impaired energy state independent of the presence of extracellular Mg2+ and that the decreased energy state is not due to the changes in [Ca2+]i, which are seen only in the absence of extracellular Mg2+. PMID- 2204684 TI - Neuronal development and migration in explant cultures of the adult canary forebrain. AB - The vocal control nucleus (HVc) of the songbird forebrain undergoes neurogenesis in adulthood, as ventricular zone precursor cells divide, and their daughter cells migrate into the subjacent forebrain and differentiate into neurons. A procedure is now described by which the migration and development of these new neurons can be directly observed in vitro, in explant cultures of the adult canary forebrain. Cultured explants have yielded extensive outgrowth of new neurons from 2 neurogenic regions of the adult songbird brain: the HVc and its adjacent dorsomediocaudal neostriatum. Immunocytochemically identified neurons were determined by 3H-thymidine autoradiography to have been newly generated in vivo, in the days preceding explantation. These cells were immunoreactive for a variety of neuron-selective antigens, including MAP-1B, MAP-2, neuron-specific enolase, synaptic vesicle protein-2, N-CAM, and the tetanus toxin and A2B5 ligands. Combined immunostaining and autoradiography of cultures derived from HVcs exposed to 3H-thymidine in vivo revealed a population of newly generated, MAP-2/3H-thymidine-positive neurons. The neurons identified in these adult explant outgrowths comprised new, recently generated postmitotic cells which had arisen in the neostriatal ventricular zone and were in the early stages of their parenchymal migration at the time of tissue explantation. Accordingly, nonneurogenic control regions, including the anterior hyperstriatum, cerebellum, and optic tectum, did not display neuronal outgrowth in culture. Only forebrain regions exhibiting neurogenesis in vivo manifested neuronal outgrowth and maturation in vitro. PMID- 2204686 TI - Neuron-specific expression of high-molecular-weight clathrin light chain. AB - High-molecular-weight forms of clathrin light chains LCa and LCb contain inserted sequences and are expressed in brain tissue but have not been observed in peripheral tissues. Monoclonal antibodies specific for the high-molecular-weight form of LCb and all forms of LCa were used to analyze their expression in different species and different neuronal cell types. High-molecular-weight light chains were found in bovine, rat, mouse, chicken, and human brain, indicating a conserved pattern of expression. Neuron-specific expression of the high-molecular weight light chains was suggested by analysis of human brain gray matter and white matter. The former contained a higher proportion of light chains with insertion sequences. Immunohistochemical analysis localized the high-molecular weight form of LCb to synapses and neuronal perikarya, but not to glial cells. Immunofluorescent labeling of cultured chicken dorsal root ganglia confirmed expression in neurons but not Schwann cells. These results indicate that the high molecular-weight forms of clathrin light chains are restricted in expression and found in neuronal cells. PMID- 2204685 TI - Neuronal subsets express multiple high-molecular-weight cell-surface glycoconjugates defined by monoclonal antibodies Cat-301 and VC1.1. AB - Cat-301 and VC1.1 are monoclonal antibodies that recognize surface-associated molecules on subsets of mammalian CNS neurons. Earlier work demonstrated that Cat 301 recognizes a 680-kDa chondroitin sulfate proteoglycan (PG). VC1.1 has been shown to recognize 3 polypeptide bands on Western blot analysis; a major band at 95-105 kDa and additional bands at 145 kDa and 170 kDa. In the present report, we show that VC1.1 also reacts with a high-molecular-weight glycoconjugate. Immunoprecipitation experiments and biochemical characterizations indicate that Cat-301 and VC1.1 define at least 3 distinct high-molecular-weight antigens. The VC1.1 antigens react with antikeratan sulfate antibodies, while the Cat-301 antigens do not. By immunodepletion, we show that some VC1.1 antigens are Cat-301 positive, while others are Cat-301 negative. In addition, Cat-301-reactive proteoglycans are heterogeneous with respect to the presence or absence of VC1.1 epitopes. Double-label immunofluorescence studies with these 2 antibodies are consistent with the biochemical results and show that there are 3 classes of immunoreactive neurons in the cat CNS:Cat-301+/VC1.1+, Cat-301-/VC1.1+, and Cat 301+/VC1.1-. These results indicate that structural microheterogeneity exists among Cat-301 and VC1.1 high-molecular-weight glycoconjugates. This heterogeneity may be a reflection of the diverse neuronal phenotypes that are recognized by Cat 301 and VC1.1 in the mammalian CNS. PMID- 2204687 TI - The avian tectobulbar tract: development, explant culture, and effects of antibodies on the pattern of neurite outgrowth. AB - The tectobulbar tract is the first long-distance projecting fiber pathway to appear during the development of the avian optic tectum (dorsal half of the mesencephalon). Immunologically stained wholemounts of the E3 mesencephalon reveal that the early tectobulbar axons course in a dorsal-to-ventral direction and abruptly turn in a caudal direction shortly before reaching the ventral midline. During subsequent development, more tectobulbar axons are generated that form a parallel array of thick fascicles coursing ventrally within the mesencephalon. At this later stage of development, the tectobulbar tract bifurcates into an ipsilateral and contralateral pathway, both growing in a caudal direction near the mesencephalic ventral midline. Bifurcation and change in direction of growth is accompanied by a complete loss of the fasciculated growth pattern. Each tectobulbar axon is thus divided into a proximal fasciculated and a distal unfasciculated segment. Tectobulbar fascicles occupy the most superficial surface layer of the mesencephalon at early stages and are displaced deeper into the tissue beginning at embryonic day 5. In both of these locations, tectobulbar axons express molecules involved in axon-axon and axon substrate interactions like the G4 antigen, neural cell adhesion molecule (N CAM), neurofascin, and T61 antigen as revealed by immunohistochemistry and immunoblotting. Stripes of the mesencephalon explanted onto a basal lamina substratum show vigorous outgrowth of neurites. These processes grow in fascicles at a growth rate of 40 microns/h. Staining of the neurites with specific antibodies, as well as the position of the retrogradely labeled cell bodies, is in agreement with these processes being tectobulbar axons. This in vitro explant system was used to investigate the expression and possible functional involvement of N-CAM, neurofascin, G4 protein, and T61 antigen in the growth of these axons. The presence of antigen-binding fragments of polyclonal anti-G4 antibodies completely blocks fasciculation of the neurites but has no influence on their rate of elongation. Antibodies against N-CAM and neurofascin have no detectable effects. The number and length of the in vitro growing axons are reduced by the monoclonal T61 antibody. This effect is reversible. The elucidation of the exact course in vivo and the accessibility to the axons growing in vitro make the tectobulbar tract an excellent model system for the investigation of the role of these and other proteins in axonal growth and guidance during the development of the CNS. PMID- 2204688 TI - 1B1075: a brain- and pituitary-specific mRNA that encodes a novel chromogranin/secretogranin-like component of intracellular vesicles. AB - The rat 1B1075 mRNA encodes a 533-residue novel chromogranin/secretogranin-like acidic protein that contains an apparent secretion signal, several pairs of tandem basic residues, and internally repeated sequence elements. 1B1075 transcripts are detected, by blotting and in situ hybridization, at the highest levels in the neocortex, hippocampus, cerebellar cortex, selected pontine and diencephalic nuclei, and presumptive pituitary corticotrophs, at lower levels in specific nuclei in most other brain regions, but in none of several other tissues. Utilizing antisera to several nonoverlapping synthetic peptide fragments of the predicted protein sequence, we detect a brain- and pituitary-specific 57 kDa protein in cellular processes and fiber tracts, generally consistent with axonal transport from the cell bodies identified by in situ hybridization. Ultrastructural studies demonstrate that this protein is a component of intraneuronal vesicles in axons and vesicle-like structures in dendrites. Based on these data, we suggest the name Secretogranin III for the 1B1075 gene product. In related collaborative studies, a mouse deleted for the 1B1075-homologous gene has been produced that should allow assessment of its physiological role. PMID- 2204689 TI - The long-term side effects of radiation therapy for benign brain tumors in adults. AB - Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors (two of these also had pituitary dysfunction). One clival tumor with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered "safe" treatment for benign brain tumors. PMID- 2204690 TI - A comparative study on ventriculographic and computerized tomography-guided determinations of brain targets in functional stereotaxis. AB - Thalamic, pallidal, and hypothalamic targets were determined in 16 patients by a stereotactic computerized tomography (CT) study using a noninvasive technique with Laitinen's Stereoadapter. At surgery, the Stereoadapter was remounted to the head and the stereotactic CT coordinates were transferred to the Stereoguide without radiography. Air ventriculography was then carried out. The positions of the anterior and posterior commissures (AC and PC), the length of the intercommissural (IC) line, the width of the third ventricle, and the stereotactic coordinates of the target were measured on the ventriculograms and compared to the stereotactic CT measurements. The study showed that the width of the third ventricle was significantly larger on the ventriculograms than on the stereotactic CT scans, whereas the length of the IC line was not significantly different. The differences in the coordinates of the target and of the AC and PC were statistically significant only for the anteroposterior (y) coordinate. Both commissures as well as the surgical target lay, on average, 1.0 mm more anteriorly on the ventriculograms than on the stereotactic CT study. It is concluded that air ventriculography may cause slight anterior displacement of the midbrain structures. The surgical coordinates of the targets based on the stereotactic CT study with the Stereoadapter were on average as accurate as those obtained with ventriculography; therefore, ventriculography may become superfluous in functional stereotaxis. PMID- 2204691 TI - Impact of vessel distortion on transcranial Doppler velocity measurements: correlation with magnetic resonance imaging. AB - Because transcranial Doppler ultrasound is a blind procedure, it is not possible to routinely correct for insonation angle errors, which are presumed to be small. In anatomically normal brains this is a valid assumption; however, in some patients with distorted vascular anatomy (as in hydrocephalus) a small insonation angle cannot be assumed, and measurements of flow velocity may be misleadingly low. The orientation of the middle cerebral arteries was studied on magnetic resonance images of 17 control patients and three patients with hydrocephalus, and estimates of insonation angle errors in velocity measurements were made. When asymmetrical vessel distortion is present, relative flow to each hemisphere may not be accurately reflected in the measured velocities. Under these circumstances, the resistivity index may be a more reliable hemodynamic parameter. PMID- 2204692 TI - Bilateral femoral nerve neuropathy following blunt trauma. Case report. AB - A unique case of bilateral compressive injury of the femoral nerves is reported in a 19-year-old man. Traumatic femoral nerve neuropathy following operative injury, penetrating injury, anticoagulant therapy with hemorrhage, and stretch injury has been described previously, and the literature concerning this unusual clinical problem is reviewed. Bilateral traumatic femoral nerve neuropathy resulting from compressive injury has not been previously reported. PMID- 2204693 TI - Perineal care. Then and now. AB - Since the late nineteenth century, the average postpartum woman has been subjected to a great deal of swabbing, soaking, and spraying, all in the name of perineal care. Many elaborate regimens have been devised to prevent infection, promote healing, and provide comfort to the mother, often based on little physiologic rationale or research data. All of these regimens have taken away valuable time and energy that the new mother needs for more important tasks. A review of past and current perineal care practices and major research studies relative to perineal care can form a foundation from which to evaluate and update the management of perineal care. PMID- 2204694 TI - Effect of manganese deficiency on insulin binding, glucose transport and metabolism in rat adipocytes. AB - The effect of manganese deficiency on insulin binding, glucose transport and metabolism in isolated adipose cells from Sprague-Dawley rats was investigated. Offspring from Mn-sufficient female rats fed 45 micrograms Mn/g diet (control) and from Mn-deficient (Mn-) female rats fed 1 microgram Mn/g diet were used in these studies. Both basal and insulin-stimulated 3-O-methylglucose transport in isolated adipose cells was significantly lower in Mn- rats, averaging 40% and 50% of control values, respectively. Kinetic analysis of glucose transport demonstrated a lower maximal transport velocity (Vmax) for glucose in adipose cells from Mn- rats compared to controls. No differences in the Km for glucose uptake were observed between the two groups. Insulin-stimulated glucose oxidation to CO2 and conversion to triglycerides was lower in isolated adipose cells from Mn- rats compared to controls. Mn- animals had fewer insulin receptors per cell compared to controls, although no differences in insulin receptor affinity were observed between the two groups. These data suggest that Mn deficiency affects glucose transport and metabolism in the adipose cell. The apparent defect lies distal to the insulin receptor and probably reflects a decreased number of glucose transporters in adipose tissue of Mn- rats. PMID- 2204695 TI - Nutrition-induced variations in responsiveness to insulin effects on lipoprotein lipase activity in isolated rat fat cells. AB - The effect of insulin on the regulation of lipoprotein lipase (LPL) activity in isolated adipocytes from rats in various nutritional states was studied. Because LPL is secreted from adipocytes, possible insulin effects on LPL activity were assessed as 1) total cellular LPL activity, 2) LPL activity spontaneously secreted during incubations and 3) LPL secretion during perifusion of adipocytes preincubated with or without insulin. Incubation with insulin for 2 h produced no increase in LPL activity associated with adipocytes isolated from 5- to 6-wk-old fasted rats but increased by 83% the activity of LPL secreted into the incubation medium. Insulin pretreatment increased by 230% the capacity of the cells to secrete LPL activity when perifused in the presence of 5% fasted human serum. In adipocytes from young rats killed in the fed state, preincubation with insulin caused a small increase in cell-associated LPL activity (+21%) but no increase in LPL activity spontaneously secreted into the incubation medium. Similar to results in fasted rats, insulin-pretreated cells showed a 101% increase in their ability to secrete LPL activity during a perifusion. In contrast, larger adipocytes from 3-mo-old rats were totally unresponsive to insulin effects on both cellular and secreted LPL. However, 3 d of fasting followed by 9 d of refeeding restored responsiveness to insulin effects on both cellular and secreted LPL activity. Thus, variations in cellular responsiveness to insulin effects on LPL activity may play an important role in regulating nutrition induced changes in LPL activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2204696 TI - Quality of life after heart transplantation in patients assigned to double- or triple-drug therapy. AB - The purpose of this study was to compare the quality of life after heart transplantation for patients treated with cyclosporine and azathioprine (double therapy) versus cyclosporine, azathioprine, and corticosteroids (triple therapy). This study was based on a randomized, prospective trial and was focused on patients from ages 17 to 57 years at 1-year after transplantation. Patients who received double therapy showed advantages on 10 of 11 measures of quality of life. Significant differences were found on measures of anxiety, sexual activity, physical well-being, and financial well-being. Patients who received double-drug therapy reported a lower frequency and less distress from the side effects of immunosuppression; a higher proportion of double-drug therapy patients had returned to full-time employment. In addition double-therapy patients were better able to control body mass. These features may explain why double-drug therapy patients reported a higher quality of life, and in the long term, could be important from a cost benefit analysis. PMID- 2204697 TI - HIV-associated autoimmune hemolytic anemia: report of a case and review of the literature. AB - While anemia and a positive direct anti-globulin test are each frequently observed in the clinical syndrome of human immunodeficiency virus (HIV) infection, autoimmune hemolytic anemia has rarely been reported in this setting. A case of severe warm autoimmune hemolytic anemia (AIHA) with reticulocytopenia in a patient with AIDS-related complex is reported. Laboratory and clinical findings of severe hemolysis were present, including anhaptoglobinemia, microspherocytosis, splenomegaly, and transfusion dependence. Azidothymidine (AZT) therapy may have exacerbated this patient's anemia. Splenectomy produced a delayed but complete remission of the AIHA despite continuation of AZT therapy. Review of other reports of positive direct antiglobulin tests and autoimmune hemolytic anemia in patients with HIV infections suggests that autoantibodies may be a significant cause of anemia in this population and that the frequent lack of reticulocytosis, despite bone marrow erythroid hyperplasia, may lead to the underdiagnosis of AIHA in HIV-infected patients. PMID- 2204699 TI - An introduction to the study of xenobiotic metabolism using electroanalytical techniques. PMID- 2204698 TI - Salivary antibodies to human immunodeficiency virus type 1 in a phase I AIDS vaccine trial. AB - HIV-1-specific secretory antibodies may be a desirable outcome in individuals receiving AIDS vaccines. We investigated parotid and whole saliva samples for HIV specific antibodies collected from five volunteers who received a recombinant HIV 1 envelope glycoprotein (rgp160) vaccine. Ten healthy, adult volunteers received intramuscularly either three doses of rgp160 (40 or 80 micrograms), a hepatitis B vaccine, or a placebo on days 0, 30, and 180. Saliva samples were collected on days 0, 28, 60, 120, 194, and 270 from the volunteers. All volunteers were negative for serum HIV antibodies by ELISA (Abbott). By Western blotting, serum antibodies to envelope antigens were demonstrated in one of three individuals who received the low dose vaccine and two of two who received the high dose. Antibodies to gp160 were detected in whole saliva on day 194 from one of these individuals by Western blotting. Parotid saliva collected on all dates did not contain detectable HIV-specific antibodies. The finding of HIV-1-specific antibodies in whole saliva following vaccination may indicate that development of mucosal immunity is possible. PMID- 2204700 TI - Schizophrenia research update: implications for nursing. PMID- 2204701 TI - A low-cost computer-assisted teaching package for kidney dialysis: a preliminary report. AB - This paper describes a low-cost system, comprising software and a video interface unit, for interactive computer-aided learning for renal dialysis. The system is designed for use with IBM PC compatibles. The main aim of the package is to provide a teaching aid, to be used in conjunction with conventional techniques, for teaching the concepts relevant to renal dialysis. The system has been designed to be of benefit to groups such as patients, nurses and renal technicians and is suitable for users who have differing levels of expertise ranging from novice through to expert. The software is also designed to facilitate updating as new techniques and technologies become available. PMID- 2204702 TI - Comments on: 'Classification of images of biomolecular assemblies: a study of ribosomes and ribosomal subunits of Escherichia coli'. AB - In a recent paper Frank et al. (1988; J. Microsc. 150, 99-115) proposed the use of a hybrid clustering technique to sort macromolecular images. In contrast to the claims made in that paper, however, the proposed technique is less sophisticated than the enhanced hierarchical ascendant classification technique proposed by us a few years earlier. The hybrid approach will lead to partitions which are less optimal in terms of minimizing the total intra-class variance for a predetermined number of classes, irrespective of whether the data show distinct clusters or, rather, possess a quasi-continuous intrinsic structure. PMID- 2204703 TI - Efficient estimation of cell volume and number using the nucleator and the disector. AB - The nucleator allows the unbiased estimation of absolute structural quantities of suitably sampled, arbitrarily shaped structures from observations made from arbitrary points using isotropic probes. A number of time-saving modifications using the nucleator and the consequences of the modifications are studied in terms of their bias and efficiency. Using rat neocortex as an example, a description is given of how to estimate mean neuronal volume and total neuron number efficiently from only a few pairs of plastic sections with a thickness of about 3 microns. PMID- 2204704 TI - Sources of error in the estimation of Leydig cell numbers in control and atrophied mammalian testes. AB - The effects of assuming (i) that testicular tissue shrinks equally regardless of species or treatment at fixing and processing, (ii) that all Leydig cells in a given testis have spherical nuclei of identical size, and (iii) that testicular volume (i.e. the reference volume) is constant regardless of species or treatment, on the estimation of Leydig cell numbers in mammalian testes were investigated. This was accomplished by comparing the results of stereological analyses of Leydig cell numerical density and Leydig cell number in control testes of hamster, guinea-pig, and rat and in atrophied testes of hamster, and rat, obtained via the disector method which is unbiased with respect to the particle shape under study, and the Floderus equation which assumes that the particles under study are identical spheres. In control hamster, and also in guinea-pig, the effects of the three assumptions on the estimates of Leydig cell number per testis were negligible, because in these two treatment groups, the total shrinkage of testis tissue at fixing and processing (ST%) was low, Leydig cell nuclear profiles were circular in section, and the average volume of a testis was close to unity (i.e. 1 cm3). By contrast, in hamsters, and rats with atrophied testes, these assumptions produced incorrect estimates in Leydig cell number per testis, because the ST% was high, the majority of Leydig cell nuclear profiles were pleomorphic, and the average volume of a testis was lower than control. In summary, this study documents that the assumptions of equal shrinkage in testis tissue at fixing and processing, a constant testicular reference volume, and spheroidal shape of Leydig cell nuclei may contribute significant errors in estimates of Leydig cell number in mammalian testes. The magnitude of the errors introduced by these assumptions depends upon the species and the experimental treatment. PMID- 2204705 TI - A simple procedure for demonstrating the overall morphology of fibroblasts in routine histological preparations of adult tissues, using silver impregnation. AB - A silver impregnation procedure for the total visualization of fibroblasts, with all their processes, is described. The method is applicable to routine formalin fixed paraffin sections, or to formalin-fixed or native cryostat sections. The results are illustrated with examples from loose and dense connective tissue. Fibroblasts are visualized as cells with long, branching dendritic processes. The fibroblasts maintain contact with each other via these processes, thus forming a reticulum of cells, even in adult connective tissue. PMID- 2204706 TI - Discrimination between bacteriophage T3 and T7 promoters by the T3 and T7 RNA polymerases depends primarily upon a three base-pair region located 10 to 12 base pairs upstream from the start site. AB - The bacteriophage T3 and T7 RNA polymerases are closely related, yet are highly specific for their own promoter sequences. To understand the basis of this specificity, T7 promoter variant that contain substitutions of T3-specific base pairs at one or more positions within the T7 promoter consensus sequence were synthesized and cloned. Template competition assays between variant and consensus promoters demonstrate that the primary determinants of promoter specificity are located in the region from -10 to -12, and that the base-pair at -11 is of particular importance. Changing this base-pair from G.C, which is normally present in T7 promoters, to C.G, which is found at this position in T3 promoters, prevented utilization by the T7 RNA polymerase and simultaneously enabled transcription from the variant T7 promoter by the T3 enzyme. Substitution of T7 base-pairs with T3 base-pairs at other positions where the two consensus sequences diverge affected the overall efficiency with which the variant promoter was utilized by the T7 RNA polymerase, but these changes were not sufficient to permit recognition by the T3 RNA polymerase. Switching the -11 base-pair in the T3 promoter consensus to the T7 base-pair prevented utilization by the T3 RNA polymerase, but did not allow the T3 variant promoter to be utilized by the T7 RNA polymerase. This probably reflects a greater specificity of the T7 RNA polymerase for base-pairs at other positions where the promoter sequences differ, most notably at -15. The magnitude of the effects of base substitutions in the T7 promoter on promoter strength (-11C much greater than -10C greater than -12A) correlates with the affinity of the T7 polymerase for the promoter variants, suggesting that the discrimination of the phage RNA polymerases for their promoters is mediated primarily at the level of DNA binding, rather than at the level of initiation. PMID- 2204708 TI - DNA replication in Escherichia coli is initiated by membrane detachment of oriC. A model. AB - An adequate model for the initiation of chromosome replication in Escherichia coli should explain why the introduction of multiple copies of the chromosomal origin of replication, oriC, does not perturb cells seriously and why such multiple origins are replicated synchronously; it should explain why the key initiator protein, DnaA, is activated in vitro by binding specifically to acidic phospholipids and why the Dam methyltransferase is essential for the correct timing of initiation; it should explain why phospholipid synthesis and fluidity are necessary for initiation. In the detachment model, presented here, cyclical changes in the phospholipid composition of the cytoplasmic membrane activate initiator proteins such as DnaA protein and cause origins to detach; this detachment allows torsional stresses to open 13mer sequences in oriC; DnaA assists in the serial opening of these sequences and guides the entry of the helicase to form a pre-priming complex and trigger initiation; the greater affinity of hemi-methylated origin for membrane is re-interpreted as a mechanism for preventing re-initiation. PMID- 2204707 TI - Identification of a region of the bacteriophage T3 and T7 RNA polymerases that determines promoter specificity. AB - Bacteriophages T7 and T3 encode DNA-dependent RNA polymerases that are 82% homologous, yet exhibit a high degree of specificity for their own promoters. A region of the RNA polymerase gene (gene 1) that is responsible for this specificity has been localized using two approaches. First, the RNA polymerase genes of recombinant T7 x T3 phage that had been generated in other laboratories in studies of phage polymerase specificity were characterized by restriction enzyme mapping. This approach localized the region that determines promoter specificity to the 3' end of the polymerase gene, corresponding to the carboxyl end of the polymerase protein distal to amino acid 623. To define more closely the region of promoter specificity, a series of hybrid T7/T3 RNA polymerase genes was constructed by in vitro manipulation of the cloned genes. The specificity of the resulting hybrid RNA polymerases in vitro and in vivo indicates that an interval of the polymerase that spans amino acids 674 to 752 (the 674 to 752 interval) contains the primary determinant of promoter preference. Within this interval, the amino acid sequences of the T3 and T7 enzymes differ at only 11 out of 79 positions. It has been shown elsewhere that specific recognition of T3 and T7 promoters depends largely upon base-pairs in the region from -10 to -12. An analysis of the preference of the hybrid RNA polymerases for synthetic T7 promoter mutants indicates that the 674 to 752 interval is involved in identifying this region of the promoter, and suggests that another domain of the polymerase (which has not yet been identified) may be involved in identifying other positions where the two consensus promoter sequences differ (most notably at position -15). PMID- 2204709 TI - Black youth suicide: literature review with a focus on prevention. AB - The national rates of completed suicide in the black population between 1950 and 1981 are presented, including age-adjusted rates. Specific studies of black suicide attempters and completed suicides by blacks in several cities are discussed. Methodological problems with existing studies and national suicide statistics are presented. Proposed theories of black suicide are reviewed. Based on a summary of the characteristics of black suicide attempters reported by the literature, preventive strategies--primary, secondary, and tertiary--are presented. PMID- 2204710 TI - Solartheology, heliotherapy, phototherapy, and biologic effects: a historical overview. PMID- 2204711 TI - Pulmonary cavitation with Nocardia and Aspergillus in a renal transplant patient. AB - We present an autopsy case of concomitant pulmonary aspergillosis and nocardiosis undiagnosed during life in a long-term surviving renal transplant recipient. The patient had fever and a newly developed cavitary lesion on a chest x-ray. The working diagnosis was pulmonary tuberculosis with possible colonization by Aspergillus species. Cultures of bronchial washings became positive for Aspergillus fumigatus 1 day after death. The study of tissue from the lung cavity at autopsy revealed Aspergillus fumigatus (confirmed by postmortem culture) and the filaments of Nocardia species. Increased numbers of surviving immunosuppressed patients will require aggressive, comprehensive diagnostic techniques for the detection of polymicrobial infections. PMID- 2204712 TI - Evidence for the colocalization of the axonal mitogen for Schwann cells and oligodendrocytes. AB - Axons that normally will encounter either CNS or PNS glia have been shown to contain a powerful mitogen for both Schwann cells and oligodendrocytes. The normally nonmyelinated, nonglial ensheathed cerebellar granule cells have been shown to possess a proliferative signal for Schwann cells, suggesting that a glial mitogen is common to all axons. To determine if a glial mitogen capable of stimulating both Schwann cells and oligodendrocytes is colocalized on all types of axons we have (1) cocultured granule cells with oligodendrocytes, (2) incubated oligodendrocytes with granule cell membranes, and (3) evaluated the ability of heparin extracts of granule cell membranes, splenic nerve microsomes, and axolemma-enriched fractions isolated from rat and bovine CNS to stimulate mitosis of cultured oligodendrocytes. Neither the intact granule cells nor the granule cell membrane fraction stimulated cultured oligodendrocytes to divide. However, heparin extracts of the granule cell membranes were significantly mitogenic to the cultured oligodendrocytes. Heparin extracts of splenic nerve microsomes were more mitogenic than the comparable extract obtained from bovine CNS axolemma-enriched fractions. These results suggest that the neuronal mitogen for oligodendroglia is colocalized with the neuronal mitogen for Schwann cells. PMID- 2204713 TI - Testing ultrasonic pulsed Doppler instruments with a physiologic string phantom. AB - The spatial, temporal, and frequency resolution of conventional ultrasonic Doppler instruments and the time/space distortions in two-dimensional color Doppler imaging systems can be measured using a pulsatile moving string target. The diameter of the string is small compared with the Doppler sample volume, the velocity (speed and direction), acceleration and timing of the string motions are precisely known with reference to the R wave timing mark, and the spatial location of the string is known. A loop of surgical thread or monofilament fishline running between pulleys is driven by a motor that provides constant string speeds from 0.05 to 150 cm/s and variable string speeds programmed to mimic arterial velocity waveforms from the carotid, aortic, and femoral arteries. Constant string speeds are used to evaluate the Doppler sensitivity, frequency processing, and sample volume size; pulsatile movement of the string provides a physiologic model to evaluate the temporal performance of conventional Doppler systems and the temporal and spatial performance of two-dimensional color Doppler imaging scanners. PMID- 2204714 TI - Perinatal renal vein thrombosis. Sonographic demonstration. AB - The use of ultrasound (US) in the diagnosis of renal vein thrombosis (RVT) remains ill defined because the classical features lack specificity. The authors report three cases of renal vein thrombosis with a common US pattern: hyperechoic streaks in the interlobulary spaces confirming previous reports with the same pattern. The pattern has been observed in neonates as well as in utero. Associated vena cava thrombosis was present in two cases. This sign might be a specific sign of RVT. PMID- 2204715 TI - Intrauterine fetal growth in discordant twin gestations. AB - Twenty-five discordant twin pairs were assessed ultrasonically in a longitudinal fashion and were compared with a group of 60 concordant twin pairs. The growth parameters of the larger fetus of the discordant pair did not differ significantly from the concordant twins, while the smaller of the discordant pair exhibited a slower rate of intrauterine growth as early as 23 to 24 weeks. We conclude that (1) twins who ultimately become discordant exhibit demonstrable differences as early as 23 to 24 weeks; (2) the smaller twin in a discordant pair has a much slower rate of growth between 33 to 37 weeks; and (3) using estimated fetal weight to predict concordancy and discordancy by Shepard's and Hadlock's tables are equally efficacious, although Hadlock's table can be used more often because biparietal diameter cannot be obtained as often as femur length. PMID- 2204716 TI - Doppler blood velocity waveforms and the relation to peripheral resistance in the brachial artery. AB - The relationship between peripheral resistance and the Doppler blood velocity indices--pulsatility index (PI), A/B ratio, resistance index (RI), and the minimum velocity (Vmin)--was evaluated in the brachial arteries of five young women. All the indices showed a very good correlation with resistance (r greater than 94%); the regression line for both PI and A/B were linear, whereas the relationships between resistance and RI, and resistance and Vmin, were best described by a logarithmic and by power function, respectively. Although the women were carefully selected to be as alike as possible, there were significant differences in the individual slopes of the regression lines. PMID- 2204717 TI - Sonographic sliding sign in localization of right upper quadrant mass. AB - Sonographic sliding sign is the observation of dynamic motion of a mass against adjacent organs during respiratory movement or extrinsic pressure. We applied this sign for prospective study in nine patients, each of whom had a large posterior right upper abdominal mass arising from the liver, kidney, or adrenal gland. The sign was found to be very reliable as a criterion for the localization of the origin of the mass in all patients except in the following two cases: a Wilm's tumor that invaded the retroperitoneum and posterior abdominal wall was regarded as a retroperitoneal tumor invading the kidney; and in the other one, an adrenal pheochromocytoma, the sliding sign against the liver and the right kidney was equivocal. In conclusion, judicious use of the sonographic sliding sign will greatly assist in the localization of a large right upper abdominal mass, especially when there is a paucity or lack of retroperitoneal fat. PMID- 2204718 TI - On the application of ultrasonic contrast agents for blood flowmetry and assessment of cardiac perfusion. AB - The stability, size, and ultrasonic properties of several ultrasonic microbubble contrast agents such as Albunex, SHU-454, 1% hydrogen peroxide, and sonicated solutions such as 70% and 50% dextrose, 70% sorbitol, 5% albumin, Renografin-76, and others were evaluated. Albunex was the only tested agent that was sufficiently stable over an extended period of time for in vitro ultrasonic characterization. The attenuation and backscatter coefficients of Albunex at 5 and 7.5 MHz were found to be linearly proportional to microsphere concentration at low concentrations (less than 0.01% for attenuation and less than 0.002% for backscatter). Also, Albunex was found to be more echogenic than soft tissues at 5 MHz even after being diluted to 0.0003% of the original concentration. Next, the feasibility of using this acoustic information for contrast blood flowmetry was investigated. In vitro flow estimates in a mock flow loop were made using only the ultrasonic properties of the contrast agent. Bolus injections of Albunex and indicator-dilution curves inferred from ultrasonic measurements were used to estimate calibrated flow rate ranging from 400 to 5000 mL/min. The flow estimates from attenuation measurements showed a good correlation with those from an independent method (r = 0.97), but the results from backscatter studies did not correlate well. These results demonstrate that attenuation measurement may be a feasible alternative for in vivo blood flow measurement in conjunction with the indicator dilution principle or estimation of tissue perfusion such as myocardial perfusion using a time-activity approach. PMID- 2204720 TI - Prenatal sonographic findings associated with a fetal horseshoe kidney. PMID- 2204719 TI - Idiopathic infantile arterial calcification. In utero diagnosis. PMID- 2204721 TI - Intracellular distribution of the envelope glycoprotein of human immunodeficiency virus and its role in the production of cytopathic effect in CD4+ and CD4- human cell lines. AB - Human CD4+ and CD4- monocytoid cell lines were transfected with a constructed plasmid that has the envelope gene of human immunodeficiency virus under the transcriptional control of human metallothionein IIA promoter; the transfected cells were then cloned. These CD4+ and CD4- transfectant cell clones, both of which expressed almost the same amount of gp160 after induction with metal ions, were used for ultrastructural analysis of the distribution of the envelope glycoprotein in the cytoplasm. Immunofluorescence microscopy with an anti envelope glycoprotein monoclonal antibody showed localized distribution of gp160 in the CD4+ cell clone and diffuse distribution of gp160 in the CD4- cell clone. These observations were substantiated by immunoelectron microscopy, in which the aggregated form of gp160 was observed in the cytoplasm of CD4+ cells but was scarce in that of CD4- cells. A notable finding was that the sites corresponding to the nuclear pores were occupied with aggregates of gp160 in CD4+ cells, exhibiting cytopathic effects. Both freeze-fracture and transmission electron microscopy also showed abnormal morphology around the nuclear pores and perinuclear space. These results support the possibility that such gp160 complexes accumulated around the nuclear pores primarily disturb the transportation of many molecules between the nucleus and the cytoplasm, resulting in a cytopathic effect in the CD4+ cell clone. PMID- 2204722 TI - Analysis of mutations in the integration function of Moloney murine leukemia virus: effects on DNA binding and cutting. AB - The 3' terminus of the pol gene of Moloney murine leukemia virus encodes the integration (IN) protein, required for the establishment of the integrated provirus. A series of six linker insertion mutations and two single-base substitutions were generated within the region encoding the IN protein. Mutations were initially generated within an Escherichia coli plasmid expressing the IN protein, and the resulting variants were assayed for DNA-binding activity. Mutations which altered conserved cysteine residues within a potential DNA finger binding motif resulted in lower or variable DNA binding, which appeared to be the result of variable protein folding. Upon renaturation, these proteins were able to nonspecifically bind DNA in a manner similar to that of the other mutant IN proteins and the parent. When reconstructed back into full-length virus, seven of the eight mutations were lethal. All mutants produced a stable IN protein in virions and mediated normal conversion of the retroviral RNA to its three DNA forms. Fine-structure analysis of the linear double-stranded viral DNA indicated that all seven lethal alterations within the IN protein blocked the formation of the 3' recessed termini that normally precedes integration. PMID- 2204723 TI - Cell-specific differences in activation of NF-kappa B regulatory elements of human immunodeficiency virus and beta interferon promoters by tumor necrosis factor. AB - Three aspects of the involvement of tumor necrosis factor in human immunodeficiency virus (HIV) pathogenesis were examined. Tumor necrosis factor alpha (TNF-alpha) mRNA production was analyzed by polymerase chain reaction amplification in monocytic U937 cells and in a chronically HIV infected U937 cell line (U9-IIIB). TNF-alpha RNA was undetectable in U937 cells, whereas a low constitutive level was detected in U9-IIIB cells. Paramyxovirus infection induced a 5- to 10-fold increase in the steady-state level of TNF-alpha RNA in U9-IIIB cells compared with U937 cells, suggesting that HIV-infected monocytic cells produced higher levels of TNF-alpha than did normal cells after a secondary virus infection. The effects of TNF-alpha on gene expression were examined by transient expression assays using reporter chloramphenicol acetyltransferase plasmids linked to regulatory elements from the HIV long terminal repeat (LTR) and the beta interferon promoter. In U937 and Jurkat T lymphoid cells, the inducibility of the different hybrid promoters by TNF-alpha or phorbol ester varied in a cell type- and promoter context-specific manner; the levels of gene activity of NF kappa B-containing plasmids correlated directly with induction of NF-kappa B DNA binding activity. Although the intact beta interferon promoter was only weakly stimulated by phorbol ester or TNF-alpha, multimers of the PRDII NF-kappa B binding domain were inducible by both agents. TNF-alpha was able to increase expression of the HIV LTR in T cells, but in monocytic cells, TNF-alpha did not induce the HIV LTR above a constitutive level of activity. This level of NF-kappa B-independent activity appears to be sufficient for virus multiplication, since TNF-alpha treatment had no effect on the kinetics of de novo HIV type 1 (HIV-1) infection and viral RNA production in U937 cells. However, in Jurkat cells, TNF alpha dramatically enhanced the spread of HIV-1 through the cell population and increased viral RNA synthesis, indicating that in T cells HIV-1 multiplication was stimulated by TNF-alpha treatment. PMID- 2204726 TI - Bladder mucosa in urethral reconstructions. PMID- 2204725 TI - A mutant of human immunodeficiency virus with reduced RNA packaging and abnormal particle morphology. AB - A deletion of 30 bases was created in the noncoding region of the human immunodeficiency virus type 1 genome that extends between the 5' splice donor and the start of the gag gene. Viral particles produced after transfection of this mutant provirus had a normal protein pattern but a reduced RNA content. The infectivity of the mutant virus was also markedly reduced but not completely abolished. Electron-microscopic examination of the mutant virions revealed major abnormalities of the nucleoid structure, mostly related to the dense material characteristic of mature particles, suggesting that the presence of RNA is essential to the normal structure of the nucleoid. PMID- 2204724 TI - Regulated expression of nuclear genes by T3 RNA polymerase and lac repressor, using recombinant vaccinia virus vectors. AB - Recombinant vaccinia viruses that express the bacteriophage T3 RNA polymerase (VV T3pol) or the Escherichia coli lac repressor (VV-lacI) under control of the early late vaccinia promoter P7.5 were constructed. To determine whether phage polymerase and lac repressor can function in the nucleus of mammalian cells, the bacterial chloramphenicol acetyltransferase (CAT) gene was cloned downstream of a T3 promoter (PT3-CAT) or downstream of a T3 promoter-lac operator fusion element (PT3Olac-CAT), and these reporter gene cassettes were introduced stably into NIH 3T3 or Ltk- cells. Infection of 3T3/PT3-CAT or Ltk-/PT3-CAT cells by VV-T3pol led to rapid expression of CAT (greater than 20 ng of CAT protein per 10(6) cells). The presence of hydroxyurea (which blocks virus DNA replication) did not prevent CAT production. When 3T3/PT3Olac-CAT cells were infected with both VV-T3pol and VV-lacI (multiplicities of infection of 2.5 and 10, respectively), greater than 30-fold repression of CAT gene activity by lac repressor was observed. This could be reversed to unrepressed levels by the presence of 10 mM o-nitrophenyl-beta-D galactoside (IPTG) in the medium. Regulated expression of the target gene was observed with cell lines that had been maintained for over 1 year (greater than 50 passages in culture), and Southern blot analysis revealed the presence of the CAT gene only in the nuclear fraction in these cells, demonstrating the stability of the target gene. These results indicate that vaccinia virus-encoded proteins can function in the mammalian nucleus and provide the basis for a genetic system in which essential vaccinia virus genes, placed in the chromosome of a cell, can be used to complement defective virus particles. This approach may prove useful for other virus systems. PMID- 2204727 TI - Technique of left adrenalectomy for autotransplantation to the caudate nucleus in Parkinson's disease. AB - Autotransplantation of the adrenal medulla to the caudate nucleus is a new neurosurgical treatment under investigation for severe Parkinson's disease. The success of the procedure is reliant partly on the ability of the urologist to remove the adrenal gland safely and atraumatically with minimal morbidity. We describe our technique using a posterior 12th rib approach, which is extrapleural and extraperitoneal. In the initial 10 patients there was no significant morbidity from the operation and all patients were discharged from the hospital within 3 to 7 days postoperatively. The importance of using a no touch technique in mobilizing the gland is emphasized, since any hemorrhage within the adrenal medulla may make it impossible to recover the tissue for stereotactic implantation. Hemorrhage occurred in 1 of our patients, who was elderly and obese. The technique described allows for adequate exposure while maintaining acceptably low morbidity from the procedure. PMID- 2204728 TI - Interstitial cystitis: bladder mucosa lymphocyte immunophenotyping and peripheral blood flow cytometry analysis. AB - Interstitial cystitis is a chronic bladder disorder of unknown etiology that primarily afflicts women and is characterized by urgency and pain. Although immune mechanisms have been implicated in the disease process, little is known about the local or peripheral blood immune responses. Cryostat sections of snap frozen bladder biopsies obtained by transurethral resection from 43 patients (24 with classical and 9 with nonulcerative or early interstitial cystitis, and 10 controls) were analyzed using a panel of monoclonal antibodies with an avidin biotin immunoperoxidase technique to characterize the local immune response of bladder mucosa. Simultaneously obtained heparinized peripheral blood (10 cc) was analyzed by flow cytometry in 24 patients (9 with classical and 5 with nonulcerative early interstitial cystitis, and 10 controls) using the same panel of antibodies. The control group biopsies (median age 44 years, range 27 to 52 years) had no ulcers, few lymphoid cells (predominately T-helper cells), rare T cell nodules and no B cells. The nonulcer group (median age 39 years, range 29 to 44 years) had rare mucosal ruptures but no ulcers, slightly increased lymphoid cells (predominately T-helper), occasional T cell aggregates, no B cell nodules and rare plasma cells. No statistically significant difference between control and nonulcerative interstitial cystitis patients was identified. In contrast, the classical interstitial cystitis group (median age 68 years, range 47 to 73 years) had ulcers, intense inflammation with focal sheets of plasma cells, aggregates of T cells, B cell nodules including germinal centers, a decreased or normal helper to-suppressor cell ratio and suppressor cytotoxic cells in germinal centers. Flow cytometry analysis of peripheral blood lymphocyte subsets showed normal patterns in controls, increased numbers of secretory Ig positive B cells and activated lymphocytes in the nonulcerative group, and increased numbers of secretory Ig positive B cells with mildly abnormal kappa-to-lambda ratios and activated lymphocytes in the classical group. We conclude that an immune mechanism has at least a partial role in the pathophysiology of interstitial cystitis. A parallel between interstitial cystitis and inflammatory bowel disease is evident. Further studies are indicated. PMID- 2204729 TI - Growth fractions of transitional cell carcinomas of the bladder defined by the monoclonal antibody Ki-67. AB - We used an immunohistochemical technique with the monoclonal antibody Ki-67, which recognizes nuclear antigen expressed in proliferating cells to determine the growth fractions of 5 normal mucosa specimens and 55 transitional cell carcinomas of the bladder. Normal mucosa had a mean value of 0.37 +/- 0.35% cells positive for Ki-67, whereas 9 histological grade 1 tumors showed 2.2 +/- 1.5%, 31 grade 2 tumors averaged 10.1 +/- 7.5% and 15 grade 3 tumors yielded 19.5 +/- 9.0%. These values were significantly different from each other (p less than 0.01), with Ki-67 indexes for grade 2 varying from 0.3 to 24.6%. Nonpapillary tumors had significantly higher indexes than papillary tumors (20.1 +/- 8.0 versus 6.7 +/- 5.9, p less than 0.01). The Ki-67 indexes were 4.6 +/- 4.5% for stage Ta (20 cases), 7.8 +/- 4.7% for stage T1 (14) and 20.2 +/- 7.8% for stages equal to or higher than T2 (21). Significant differences were noted between stages Ta and T1 (p less than 0.05) and between stages T1 and T2 or greater (p less than 0.01). Tumors with muscle layer invasion often showed more than 15% Ki 67 positive cells. Our results imply that Ki-67 indexes not only provide objective information to determine a malignant potential but also help to select the treatment. PMID- 2204730 TI - Penile blood flow changes in the flaccid and erect state in potent young men measured by duplex scanning. AB - We studied penile blood flow changes with duplex ultrasound scanning in 8 potent young men during the flaccid state and during the erect state induced by visual sexual stimulation. Measured parameters obtained from the cavernous arteries were arterial diameter, peak blood flow velocity and blood flow acceleration. The mean arterial diameter change was 72% associated with average blood flow velocity and acceleration changes of approximately 200%. Actual values for blood flow velocity and acceleration were considerably higher when compared to papaverine-induced values measured in psychogenically impotent men. Visual sexually stimulated penile arterial changes are not analogous to papaverine-induced arterial changes and these differences raise questions about the appropriateness of using psychogenically impotent men as controls for measurement of penile arterial function with duplex scanning. PMID- 2204731 TI - Papaverine-induced penile blood flow acceleration in impotent men measured by duplex scanning. AB - We assessed the value of penile blood flow acceleration as a parameter in the evaluation of the penile arteries. Duplex sonography and pulsed Doppler analysis with papaverine were performed in 50 impotent men. Measured parameters included cavernous artery diameters before and after papaverine, post-papaverine peak blood flow velocity and blood flow acceleration. Erections were graded subjectively on a scale of 1 to 4, with 4 being a full erection. Penile blood flow acceleration appeared to correlate with vessel dilatability and poor erectile response, and was subjectively more discriminating than peak blood flow velocity. This parameter provides additional measurable data about arterial function and should be obtained in addition to the other 2 parameters. PMID- 2204732 TI - Preliminary evaluation of color Doppler imaging for investigation of intrascrotal pathology. AB - Color Doppler ultrasound facilitates investigation of blood flow in addition to imaging parenchymal abnormalities. To assess the clinical use of this technique we evaluated 25 consecutive patients with indications for intrascrotal imaging. Color flow imaging added useful information in all 11 patients evaluated for chronic scrotal pain and in 6 of 7 evaluated for acute scrotal pain. In contrast, color flow ultrasound provided little additional information in 7 patients with intrascrotal masses. Color flow ultrasound imaging is a promising method that may prove to be useful for assessment of selected patients with intrascrotal pathological conditions. PMID- 2204733 TI - Ureteral stump transitional cell carcinoma in a patient with recurrent superficial bladder cancer: an argument for complete nephroureterectomy in selected patients. AB - A 62-year-old white man had diffuse transitional cell carcinoma of a right ureteral stump 2 1/2 years after initial transurethral resection of a bladder tumor and right radical nephrectomy for renal cell carcinoma. This case and review of the literature suggest an indication for complete ureterectomy in nephrectomy candidates with prior or concurrent transitional cell carcinoma of the bladder. PMID- 2204734 TI - Eosinophilic cystitis presenting as invasive bladder cancer: comments on pathogenesis and management. AB - Eosinophilic cystitis is a rare bladder lesion that usually presents with hematuria and has the cystoscopic appearance of a bladder tumor. Ten cases (only 4 adults) have been reported in which this disease has presented with a palpable mass. We report a case in which the lesion presented as an invasive bladder tumor with a palpable mass in an adult and comment on the possible etiology. PMID- 2204735 TI - Renal duplex sonography: evaluation of clinical utility. AB - With the exception of conventional angiography, no previously proposed screening test has the necessary sensitivity/specificity to guide further evaluation for correctable renovascular disease. Recently, renal duplex sonography has been suggested as a useful substitute in such screening for renovascular disease. This report analyzes our data collected over the past 10 months in evaluation of renal duplex sonography to examine its diagnostic value. The study population for renal duplex sonography validity analysis consisted of 74 consecutive patients who had 77 comparative renal duplex sonography and standard angiographic studies of the arterial anatomy to 148 kidneys. Renal duplex sonography results from six kidneys (4%) were considered inadequate for interpretation. This study population contained 26 patients (35%) with severe renal insufficiency (mean 3.6 mg/dl) and 67 hypertension (91%). Fourteen patients (19%) had 20 kidneys with multiple renal arteries. Bilateral disease was present in 22 of the 44 patients with significant renovascular disease. Renal duplex sonography correctly identified the presence of renovascular disease in 41 of 44 patients with angiographically proven lesions, and renovascular disease was not identified in any patient free of disease. When single renal arteries were present (122 kidneys), renal duplex sonography provided 93% sensitivity, 98% specificity, 98% positive predictive value, 94% negative predictive value, and an overall accuracy of 96%. These results were adversely affected when kidneys with multiple (polar) renal arteries were examined. Although the end diastolic ratio was inversely correlated with serum creatinine (r = -0.3073, p = 0.009), low end diastolic ratio in 35 patients submitted to renovascular reconstruction did not preclude beneficial blood pressure or renal function response. We conclude from this analysis that renal duplex sonography can be a valuable screening test in the search for correctable renovascular disease causing global renal ischemia and secondary renal insufficiency (ischemic nephropathy). Renal duplex sonography does not, however, exclude polar vessel renovascular disease causing hypertension alone nor does it predict hypertension or renal function response after correction of renovascular disease. PMID- 2204736 TI - Initial experience with color-flow duplex scanning of infrainguinal bypass grafts. AB - Seventy-eight infrainguinal grafts were evaluated by means of color-flow duplex imaging to demonstrate its utility in the routine surveillance of leg grafts as well as in the evaluation of grafts in which a problem is already suspected. Stenoses were identified in 15 (20%) of 76 grafts evaluated for screening purposes. Seven of these had confirmatory arteriograms, and five were revised. The remaining eight grafts with suspected stenoses were followed without angiography, and four (50%) subsequently failed. Only two (3.3%) of 61 grafts with normal scan outcomes have thrombosed. Fistulas were identified in 12 (37%) of 32 in situ grafts evaluated. Nine grafts with previously suspected problems based on decreased ankle-brachial indexes were scanned, and an explanation was found, confirmed by angiogram, and corrected in six. Detection of unsuspected stenoses in five grafts requiring revision and four grafts that later thrombosed without revision, as well as identification of fistulas in 37% of in situ grafts, confirms the importance of color-flow imaging as a screening tool. PMID- 2204737 TI - Is routine duplex examination after carotid endarterectomy justified? AB - Routine follow-up of patients after carotid endarterectomy with duplex scanning is commonly practiced, yet the clinical significance of identifying those with asymptomatic restenosis is unclear. To address this issue we reviewed 120 consecutive patients who underwent 143 carotid endarterectomies from August 1983 to December 1988. One hundred one patients (118 operations) were available for clinical follow-up, and the overall incidence of recurrent symptoms was 6% (6/101). Sixty-three of these patients (78 carotid endarterectomies) had postoperative duplex examination. Two had evidence of residual disease from the time of surgery and were not included in further analysis. Significant recurrent stenosis (greater than 50% diameter reduction) developed in 14 of the remaining 76 arteries (18.2%). Twelve of 14 stenoses remained asymptomatic during follow-up from 18 to 72 months (mean 47.0 months) and did not undergo reoperation. Recurrent ipsilateral hemispheric symptoms developed in two patients with restenosis (14.3%). Four of the 62 arteries without significant recurrent stenosis developed ipsilateral symptoms (6.5%), but none required reoperation during follow-up from 1 to 71 months (mean 31.6 months). Life-table analysis showed no increased risk of transient ischemic attack, stroke, or death in patients with restenosis. This study supports regular clinical follow-up after carotid endarterectomy with emphasis on patient education in the recognition of symptoms. Although duplex scanning may be useful to follow known contralateral asymptomatic disease or evaluate those with recurrent symptoms, its routine use to identify patients with asymptomatic restenosis after carotid endarterectomy may be unnecessary. PMID- 2204738 TI - Strategies for screening blood for human immunodeficiency virus antibody. Use of a decision support system. AB - A decision analytic model was used to examine alternative strategies to screen donated blood for human immunodeficiency virus (HIV) using data from the literature and from 1987 blood-screening programs in areas with high and low prevalence of HIV. Sensitivity analyses incorporated uncertainties about HIV infection and test performance. Current screening strategies are estimated to allow 20.5 infected units per million donated units to be transfused at a cost of $16,850 per HIV-positive unit detected in high-prevalence areas and 4.7 infected units per million donated units to be transfused at a cost of $32,275 per HIV positive unit detected in low prevalence areas, with nine false-positive notifications of uninfected patients per million units screened and 14.9 discarded, noninfected units per HIV-positive unit in low-prevalence areas. Testing donated blood for HIV can be improved by individualizing screening strategies for areas with different prevalences of HIV. Efforts to further reduce transfusion-associated HIV should focus on improved test performance in early stages of infection, reduction of unnecessary transfusions, donor recruitment in lower-risk groups, and public health measures to reduce HIV infection among the general population. PMID- 2204739 TI - Low-dose aspirin for migraine prophylaxis. AB - The Physicians' Health Study is a randomized, double-blind, placebo-controlled trial that studied low-dose aspirin (325 mg every other day) therapy among 22,071 US male physicians aged 40 to 84 years. Annual follow-up questionnaires requested information on the occurrence of numerous medical conditions including migraine. At the end of 60 months, morbidity follow-up was 99.7% complete, and the reported consumption of aspirin or other platelet-active drugs was 86% in the aspirin group and 14% in the placebo group. Of those randomized to aspirin, 661 (6.0%) reported migraine at some time after randomization, as compared with 818 (7.4%) of those allocated to the placebo group, representing a statistically significant 20% reduction in recurrence rate. The rate of self-report of ordinary headache was similar in the two groups. These data indicate that migraine is mediated, at least in part, by the effects of platelets and suggest that low-dose aspirin should be considered for prophylaxis among those with a history of established migraine. PMID- 2204740 TI - Antibody-targeted thrombolytic agents. AB - Plasminogen activator therapy for acute myocardial infarction has become standard medical practice. Bleeding complications, however, limit the utility of the currently available agents. This article reviews how the tools of immunology, molecular biology and protein engineering are being used to develop safer and more effective plasminogen activators. PMID- 2204741 TI - [Gynecomastia in children]. AB - The experience with treatment of 34 children with gynecomastia is summarized. The examination included roentgenography of the Turkish saddle, definition of bone age, investigation of buccal sex chromatin, excretion of 17-ketosteroids, excretory urography against the background of retropneumoperitoneum, ultrasound investigation of the mammary glands. In juvenile gynecomastia, the mammary glands were removed, the expectant tactic being considered unwarranted. The long-term results of the surgical treatment are good. PMID- 2204742 TI - [Lymphatic system during inflammation and surgical aggression]. PMID- 2204743 TI - [Organizational and tactical problems of the treatment of patients with severe multiple trauma of the abdominal organs]. PMID- 2204744 TI - [Foreign body migration in the digestive canal]. PMID- 2204745 TI - [Unusual migration of silk ligatures]. PMID- 2204746 TI - [Intraoperative abdominal echography]. AB - Results of the use of abdominal intraoperative echography are reported for the first time in this country. The diagnostic precision, the scanning technique and the problems encountered in examining 56 patients are discussed. The high value of the method in small hepatic tumors, hepatic cysts and abscesses, common bile duct calculosis and pancreas cancer is pointed out. In operative interventions on gastrointestinal neoplasms intraoperative echography may be used for continuing surgical palpation into the butt. To master the method and introduce it as a routine method in clinical practice it is necessary, to use modern equipment, to be skilled in scanning technique and to have thorough knowledge on the characteristics of the intraoperative images of the different pathologic processes. PMID- 2204747 TI - [The microsurgical treatment of lymphedema of the extremities]. PMID- 2204749 TI - [The successful surgical correction of a neglected case of a complicated rectovestibular fistula in a 13-year-old girl]. PMID- 2204748 TI - [The procedure and treatment of acute cholecystitis in young people]. PMID- 2204750 TI - [The use of a new plastic method for consolidating a preternatural anus as prevention in paracolostomy hernias]. AB - Once the stage of extraperitoneal evasion of the sigmoid has been achieved for definitive preternatural anus, transsection is made of the aponeurosis of m. obliqu. ext. abdominis along its tendon fibers at a length of 5-6 cm. Then an aperture is made along the muscle fibers with the same length on m. obliqu. int. abdominis and m. transversus abdominis as well and finally f. transversalis is transsected. The peritoneum is intra-abdominally detached from the fascia beneath and alongside the aperture. An "Ampoxen" layer is placed around the internal aperture of the abdominal wall. The explant is sutured to the fascia and the evaded sigmoid. The latter is sutured to the aponeurosis of m. obliqu. ext. abdominis. Another Ampoxen layer is placed over this aponeurosis and sutured to the evaded intestine and in a chess-board way to the fascia. The method was applied in 22 patients with very good postoperative result. PMID- 2204751 TI - [Clinical interpretation of the results of the studies of gallbladder contractility]. AB - Gallbladder contractility was assessed using ultrasound in 111 patients with biliary pathology and 34 normal controls. The original and literature data show that food stimulus-induced contractility of the gallbladder is related to the pattern of gastric evacuation, duodenal mucosa status, nervous regulation, morphological inflammatory and sclerotic lesions in the gallbladder wall. Echographic evaluation of motor-evacuatory function of the stomach contributes to more accurate interpretation of the contractility. Hypotonic biliary dyskinesia is thought nonidentical to hypomotor dyskinesia. These disorders reflect different aspects of gallbladder dysfunction. PMID- 2204752 TI - [Surgical treatment of hiatal hernia]. PMID- 2204753 TI - [Experience with diagnosis and treatment of infectious diseases in extreme conditions (on the 45th anniversary of victory in World War II)]. PMID- 2204754 TI - [History of the studies of shock on the fronts of World War II 1941-1945]. PMID- 2204755 TI - [Reminiscences of an Army therapist]. PMID- 2204756 TI - [Prominent military surgeon N.N. Elanskii]. PMID- 2204757 TI - [Physical methods of the treatment and rehabilitation of the wounded and sick patients during World War II]. PMID- 2204758 TI - [Ecological changes and human heredity]. PMID- 2204759 TI - [To the readers of the journal "Klinicheskaia meditsina"]. PMID- 2204760 TI - [Current methods of diagnosis of pulmonary heart disease]. PMID- 2204761 TI - [The great victory of the Soviet people]. PMID- 2204762 TI - [Soviet internists during World War II]. PMID- 2204763 TI - [Use of new mixtures of medicinal plants in the treatment of chronic bronchitis]. AB - Three new prescriptions of drug plants were included into combined hospital treatment of 156 patients with chronic bronchitis. Each of the three mixtures was to treat a certain clinical form of chronic bronchitis being composed of plants with specific mechanism of action. The mixture was taken a tablespoonful 8-10 times a day. Pronounced and moderate effect of the therapy was achieved in 95.6% of those treated. This justifies the use of the mixtures as an adjuvant therapy in basic treatment of chronic bronchitis. PMID- 2204764 TI - [Comparison of ultrasonic and clinico-functional indicators of the status of the pancreas in patients with chronic pancreatitis]. AB - Upon examination of 85 patients with chronic recurrent pancreatitis there appeared a clear cut correlation between the ultrasonic findings and clinical, laboratory and intraoperative evidence indicative of chronic pancreatitis. It should be noted that ultrasonic amplitude histography was a pilot experience in relation to pancreatic investigation. Ultrasonic criteria as a whole were insufficiently informative for definite recognition of the disease phase (aggravation or remission of chronic pancreatitis), while the peak value of ultrasound amplitude histogram of the pancreas allowed differentiation of the severity (moderate or grave) of the excretory pancreatic insufficiency. PMID- 2204765 TI - A history of the William S. Hall Psychiatric Institute. PMID- 2204766 TI - Establishing brain death in South Carolina: a clinician's guide. AB - With recent technological and medical advances, basic cardiopulmonary function can now be prolonged in many patients. Concurrently, organ transplantations have become more common and interest in living wills has increased. As a result, the South Carolina physician is increasingly obligated to determine whether a patient receiving cardiopulmonary support is dead due to irreversible cessation of brain function (ICBF) (brain dead). Here we review the bedside clinical valuation of brain death (ICBF), the adjunctive use of the EEG and other tests, and the South Carolina laws pertaining to this complex decision. PMID- 2204767 TI - Myasthenia gravis: a review with emphasis on the potential role of thymectomy. AB - Review of our results with thymectomy for myasthenia gravis supports the role of early surgery for this debilitating and often lethal disease. The data presented here confirm the fact that thymectomy has rare complications and low operative mortality. Approximately 80 percent of patients with myasthenia gravis can expect clinical improvement with surgery, which also offers a chance for complete remission. PMID- 2204768 TI - Tolerance to endotoxin in vitro: independent regulation of interleukin-1, tumor necrosis factor and interferon alpha production during in vitro differentiation of human monocytes. AB - Bacterial lipopolysaccharide (LPS)-induced production of three known endogenous pyrogens, interferon alpha (IFN-alpha), interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) was studied during in vitro differentiation of human peripheral blood monocytes. In freshly seeded cells, secretion of IL-1 and TNF alpha, but not IFN-alpha were readily induced by LPS. After 24 hr and for up to 14 days of culture, monocytes became irreversibly tolerant to LPS for the release of IL-1. IFN-alpha secretion was not induced by LPS in cells cultured for up to 8 days. Monocytes also became tolerant to LPS for TNF-alpha production 48 hr after an initial stimulation with LPS. This tolerant state, however, was transient, lasting from 6 to 8 days, after which competence for TNF secretion resumed. These observations demonstrate that regulation of production of IL-1, TNF-alpha and IFN alpha by human mononuclear phagocytes is mutually independent, related to the stage of cell differentiation and modulated by cell stimulation. Since in vitro tolerance to LPS mimics the in vivo tolerance to LPS with respect to fever, we speculate that they are closely related. PMID- 2204769 TI - Response of murine cell lines to an IL-1/IL-2-induced factor in a rat/mouse T hybridoma (PC60): differential induction of cytokines by human IL-1 alpha and IL 1 beta and partial amino acid sequence of rat GM-CSF. AB - We analyzed the proliferative response of the growth factor-dependent murine cell lines FDCp1, DA1-a, 32DC1, Ea3.15, 7TD1, BCL1 and of femural bone marrow cells for their sensitivity to various cytokines, viz. rhIL-1 beta, rhTNF, rhIL-2, mIL 3, rmIL-4, rmIL-5, rhIL-6, rhG-CSF and rmGM-CSF. We also tested for IL-1 and TNF mediated cytokine secretion by several T cell lines and thymocytes. In all T cell systems, IL-1 alpha and IL-1 beta were equally active in the induction of cytokine production, except for the rat/mouse T cell hybridoma PC60. This cell line exhibited a 10-fold difference in specific activity for the induction of cytokine secretion between rhIL-1 alpha and the other human or murine IL-1 species. Furthermore, IL-1 and IL-2 synergistically induced PC60 cells to produce a factor, which was preferentially active on FDCp1-cells, provisionally called FDCp1-growth factor. SDS-PAGE analysis of partially purified FDCp1-GF showed 19 kDa and 24 kDa-associated biological activities. Amino-terminal and internal amino acid sequences of both bands were determined and on this basis, we identified FDCp1-GF as rat GM-CSF. PMID- 2204770 TI - [A new osteoclast inhibitor is useful in the treatment of severe hypercalcemia]. PMID- 2204771 TI - [Carpal tunnel syndrome--easy to treat but the etiology is unclear]. PMID- 2204772 TI - [Serous cystadenoma and mucinous cystadenoma/cystadenocarcinoma of the pancreas. Clinical manifestation, diagnostic procedure and therapeutic concept]. AB - Cystic neoplasms are rare but in the last ten years more frequently detected tumors of the pancreas. The clinical symptoms as abdominal pain, abdominal mass, diarrhoea or weight loss are rather unspecific. There are no typical laboratory findings. Localization, size and cystic character of these tumors are well documented by ultrasound or abdominal computed tomography while typical features in CT as well as US-guided fine needle biopsy may contribute to further differentiation of the tumors. Exocrine and endocrine pancreatic function are frequently weakened which might falsly lead to the diagnosis of chronic pancreatitis. Because of their malignant potential mucinous cystadenoma should be treated by complete surgical resection while serous cystadenoma are exclusively benign and might therefore be treated conservatively in uncomplicated cases or high-risk patients. The prognosis of pancreatic cystadenocarcinoma is obviously better compared to adenocarcinoma of the pancreas. PMID- 2204773 TI - [Cognitive function in alcoholics in a double-blind study of piracetam]. AB - The effects of piracetam on cognitive functions have been studied in alcoholic patients. The investigation was carried out on 27 alcoholics who were admitted to hospital with acute withdrawal syndrome. The trial was performed under double blind condition. Thirteen patients were treated with piracetam and 14 with placebo. The performance of patients treated with piracetam (experimental group) was significantly better at the Block-Design retest, as compared with the control subjects. This was associated with comparatively good perceptual organization, visual motor coordination and abstract reasoning in these patients. Similar kind of performance of these patients has been achieved in the tests used to measure psychomotor speed and attention capacity. Our findings agree well with some observations of the clinicians and may stimulate further research in this field. PMID- 2204774 TI - [Pathophysiology of atherosclerosis. I. The morphology and developmental levels of atherosclerotic changes]. AB - The authors present an up-to-date review on natural history of atherosclerosis. After a short introduction dealing with history of atherosclerosis research, data about morphology and pathology of the normal arterial wall are presented. Special attention is focused on structural differences of arteries in different body districts as well as vascular endothelium and smooth muscle cells and their role in atherogenesis. Pathogenetic mechanisms in the evolution of lesions and morphology of different types of atherosclerotic lesions based on cellular and metabolic changes are explained in details: early lesions such as gelatinous elevations-insudative lesions, fetty dots and streaks and microthrombi; advanced lesions such as fibromusculoelastic lesions, pearly-white fibrous atherosclerotic plaques and atheromatous plaques; and complicated lesions with calcifications, ulcerations, thrombosis and hemorrhage. PMID- 2204775 TI - [Sanatoria in Split]. AB - In 1904, the first private surgical sanatorium in the Slavic South was founded in Split by Jaksa Racic, M.D., surgeon, urologist and radiologist. He was conferred degree in Insbruck "sub auspiciis imperatoris" in 1900. The sanatorium had 14 beds, operating theaters for aseptic and septic surgeries, the most modern devices, instruments, roentgenograph and electric light (17 years before Split was supplied with electricity). Doctor Jaksa Racic contributed a lot to the development of Marjan as city-park. All those achievements of Dr. Jaksa Racic were often reported in the Yugoslav and foreign newspapers. Doctor Vladimir Roic opened his own private surgical sanatorium in Split in 1929. His sanatorium had 20 beds, operating theater, delivery room and roentgenograph. In 1933 Dr. Jakov Milicic opened gynecological and obstetric sanatorium in Split. His sanatorium had 15 beds, operating theater, delivery room and roentgenograph. Those three sanatoriums, founded at the beginning of this century, with the first surgical sanatorium of Dr. Jaksa Racic, in 1904, have been of great importance for the development of health services in Split, in general. PMID- 2204776 TI - [Changes in left ventricular function and structure in hypertensive patients treated with methyldopa and urapidil]. AB - In a randomized cross-over and double-blind trial twenty mild-to-moderate hypertensives (11 males, 9 females, mean age 48.4 +/- 7.6 years) were receiving methyldopa (250 mg b.i.d.) or urapidil (30 mg b.i.d.) for 7 weeks and then treated with alternative drug for additional 7 weeks, separated by one week of wash-out period. Both antihypertensives induced significant reduction (P less than 0.01) in systolic and diastolic arterial pressure, while no significant changes (P greater than 0.20) in the body weight and the heart rate were observed. The echocardiographic features of left ventricular hypertrophy (LVH) did not decrease significantly (P greater than 0.05) on either drug, except for the left ventricular posterior wall thickness (LVPWd), which decreased on methyldopa from 10.4 +/- 1.3 to 9.8 +/- 1.4 mm (P less than 0.05). The drugs under study did not change significantly the echocardiographic indices of left ventricular function. Echocardiography resulted to be more sensitive in detecting LVH than electrocardiography. It is concluded that methyldopa might successfully reduce LVH, while direct and indirect vasodilators (such as urapidil) are less effective. PMID- 2204777 TI - [The tumor lysis syndrome: case report and review of the literature]. AB - Tumor lysis syndrome is specific acute renal failure. This syndrome is usually a complication of cytostatic therapy in patients with acute lymphoblastic leukemia and lymphoblastic lymphoma. Tumor cell lysis following chemotherapy may lead to metabolic complications and renal failure. We report herein, two patients with acute lymphoblastic leukemia who developed tumor lysis syndrome after chemotherapy. Furthermore, we describe important measures to prevent tumor lysis syndrome in high risk patients. PMID- 2204778 TI - Adjuvant immunotherapy in patients with melanoma: a new approach. PMID- 2204779 TI - Diabetic retinopathy: recent advances to eliminate treatable blindness. AB - Recent advances in the management of diabetic retinal vascular disease are of potentially great benefit to the patient. The primary care physician plays an increasingly important and responsible role in directing patients to the care they need to help preserve their sight. PMID- 2204780 TI - Nonparasitic splenic cysts. AB - The ultrasound modality, the Scintiscan with technetium, and the CAT scan may make the diagnosis and may pinpoint the location of the splenic cyst. Physical examination may reveal no abnormalities. In some cases a mass may be palpable in the LUQ. Bulging of the left lower intercostal spaces has been reported. The diaphragm may exhibit impaired motion and elevation. Percussion and auscultation of the chest may reveal secondary pulmonary findings. PMID- 2204781 TI - Mental abnormality and criminality--an uncertain relationship. AB - Some aspects of the uncertain relationship between mental abnormality and criminality are considered. Comments are offered on the contextual framework for such a relationship, studies of penal and other populations and the relationship between some specific mental abnormalities and criminal behaviour. Some implications for management are identified. PMID- 2204782 TI - [Occupational exposure to electromagnetic fields of extremely low frequency (with particular regard to power plants) and the health status of workers, based on a literature review]. AB - Recently a number of studies were carried on concerning malignant neoplasms, mainly leukemia, in workers exposed to electromagnetic fields. The studies focused upon power industry workers operating transmission--distribution lines, power stations, transformer stations and distribution substations which work at power--line frequencies. A review of selected literature was prepared concentrating on the methods describing conditions of exposure to e-m ELF fields as well as on the results of epidemiological studies. Also, the results of experiments carried on in Poland based on materials accessible only to a compact group of power industry experts were presented. PMID- 2204783 TI - Mutagenic evaluation of some triazino indoles using the Salmonella/mammalian microsome assay. AB - The mutagenicity of ethyl 1,2,3-triazino[5,4-b]indole-4-carboxylate N(3)-oxide (D3) and 2-chloroethyl 1,2,3-triazino-[5,4-b]indole-4-carboxylate N(3)-oxide (D4), heads of series of new products with considerable platelet antiaggregating and hypotensive activity, and their precursors 2-ethoxy-carbonylmethyl-1 methylindole-3-carboxylic acid (A3) and 2-(2-chloroethoxycarbonylmethyl)-1 methylindole-3-carboxylic acid (A4) were tested in four strains of Salmonella typhimurium (TA98, TA100, TA97 and TA102) using the standard plate incorporation technique. A3 and A4 were not mutagenic whereas D3 was mutagenic to all the strains and D4 was mutagenic to TA97, TA98 and TA100. The addition of 4 or 10% of S9 mix decreased the mutagenic activity of both compounds. This effect was independent of the concentration of S9 in the S9 mix. PMID- 2204784 TI - Antimutagenic activity of some saponins isolated from Calendula officinalis L., C. arvensis L. and Hedera helix L. AB - Thirteen saponins were isolated and identified from Calendula officinalis, C. arvensis and Hedera helix. Mutagenic and antimutagenic activities of these products were investigated using a modified liquid incubation technique of the Salmonella/microsomal assay. The Salmonella tester strain TA98 +/- S9 mix was used. Screening of the antimutagenic activity was performed with a known promutagen: benzo-[a]pyrene (BaP) and a mutagenic urine concentrate from a smoker (SU). Antimutagenic activities were also compared with the activity of chlorophyllin. All the saponins were found to be non-toxic and non-mutagenic for doses of 400 micrograms. Chlorophyllin inhibited the mutagenic activities of BaP (1 microgram) and SU (5 microliters) in a dose-dependent manner. The four saponins from C. arvensis and the three saponins from H. helix showed antimutagenic activity against BaP (1 microgram) and SU (5 microliters) with a dose-response relationship. The possible mechanism of the antimutagenic activity of saponins is discussed. PMID- 2204785 TI - Strong antimutagenic effect of caffeine on 9-aminoacridine-induced frameshift mutagenesis in Escherichia coli K12. AB - Caffeine, present at a concentration of 3 mg/ml during treatment with 100 microM 9-aminoacridine (9AA) of wild-type Escherichia coli K12, caused a decrease in the yield of frameshift reversions of more than three orders of magnitude. Antimutagenesis of caffeine was shown to be due to partial inhibition of induction by 9AA of frameshift replication errors, resulting in an increased efficiency of mismatch repair of the pre-mutations produced under these conditions. PMID- 2204786 TI - Infantile autism and Wernicke's encephalopathy. AB - In this paper I discuss evidence that brain damage in infantile autism may involve the same complex of brainstem nuclei that are damaged by alcohol abuse, thiamine deficiency, and asphyxia. These are metabolically the most active structures in the brain, which makes them vulnerable to many injurious factors. It is my belief that the high metabolic rate in the brainstem nuclei could support a control function for multiplexing of neural pathways, and that if this control is lost it may result in the defects of awareness and responsiveness seen in autistic children. PMID- 2204787 TI - Interactions between non-symmetric mechanical vector forces in the body and the autonomic nervous system: basic requirements for any mechanical technique to engender long-term improvements in autonomic function as well as in the functional efficiency of the respiratory, cardiovascular, and brain systems. AB - There are known anatomical asymmetries in the respiratory, cardiovascular, and nervous system. The coupling mechanisms between each of these systems--lungs heart, heart-brain, and lungs-brain--are also asymmetrical. There is a growing body of literature indicating that mechanical pressure asymmetrically applied to certain areas of the human body produces changes in the balance of autonomic parameters. These findings implicitly indicate that not only magnitude but also the direction and point of application of the force play a role in its influence upon the autonomic nervous system. Therefore, we suggest that asymmetrical vector forces resulting from the mechanical activity of the lungs, heart and blood moving throughout the circulatory system, will also produce a lateralization effect in autonomic balance. We postulate the existence of negative feedback loops between brain autonomic control and mechanical functions in the body as a fundamental part of the body's homeostatic mechanisms. It follows that any mechanical assist to the respiratory or cardiovascular system will be significantly reduced or even eliminated if these homeostatic mechanisms are not taken into account. Our hypothesis predicts that a long-term improvement in autonomic balance as well as in respiratory, cardiovascular, and brain function can be achieved if mechanical forces are applied to the body with the aim of reducing existing imbalances of mechanical force vectors. This technique implies continually controlling for precise timings resulting from physiological periodical forces as well as factors derived from anatomical and coupling asymmetries in the respiratory, cardiovascular, and nervous systems. PMID- 2204788 TI - Theories on the promotion of CNS transplant integration by selective activation of presynaptic enzyme cascades: prospects for future clinical applications. AB - It is hypothesized that multiple parallel presynaptic enzyme cascades act concertedly to regulate synaptic plasticity. These enzyme cascades include phospholipases A2 and C, protein kinase C, calcium/calmodulin and cAMP-dependent protein kinases and adenylate cyclase. New putative neurotrophic agents are postulated based on their ability to activate these enzymes. The artificial induction and amplification of multiple presynaptic enzymes in the fetal graft mature host CNS tissue complex should maximally augment axon growth and synaptogenesis. In turn this would lead to enhanced transplant integration and hence maximal functional neurologic restoration. These enzyme cascades could be stimulated in-vivo by the intraventricular infusion of receptor-specific and/or lipophilic neurotrophic agents as well as by the application of external electric fields. A theoretical construct is formulated for developing future grafting experimentation with the hope of ultimately applying these concepts to the amelioration of human neurodegenerative diseases. PMID- 2204790 TI - A physical approach to coeliac disease. AB - The morphological changes used to confirm a diagnosis of coeliac disease (CD) are precisely those predicted if the surface energy of the interface between duodenal epithelium and the luminal contents were raised to levels comparable to those demonstrated by the hydrophobic nature of the stomach wall. This hypothesis pursues the concept that, in coeliac patients, the gastric mucosal barrier (GMB) is effectively extended from the stomach to coat the duodenum, thus closing the window of absorption in the Gl tract. If studies are correct which indicate that the GMB is a physical reality provided by an adsorbed monolayer of surface-active phospholipid (surfactant) which renders surfaces hydrophobic, then it could also act as a barrier to the absorption of nutrients in the duodenum. Gluten, or its more active polypeptide fragment gliadin, exacerbates the situation in CD by acting as very effective carriers for the insoluble phospholipid which is deposited at the duodenal surface where they are digested by brush-border and pancreatic enzymes. PMID- 2204789 TI - Post-viral fatigue syndrome, viral infections in atopic eczema, and essential fatty acids. AB - Three clinical observations relating to viral infections are well-known but poorly understood. These are: the susceptibility of people with atopic eczema to viral infections; the occasional precipitation of an atopic syndrome by viral infections; the occurrence of a fatigue syndrome following viral infections. A unifying hypothesis is presented which explains these observations in terms of the interactions between viral infections and essential fatty acid (EFA) metabolism. Key elements of the hypothesis are the facts that interferon requires 6-desaturated EFAs in order to exert its anti-viral effects, that people with atopic eczema have low levels of 6-desaturated EFAs, and that viruses, as part of their attack strategy, may reduce the ability of cells to make 6-desaturated EFAs. The hypothesis has practical implications for the treatment of patients with viral infections. PMID- 2204791 TI - The multifactorial role of ATP in repair processes and radioprotection. AB - Endogenous ATP as a source of energy appears to play an important role associated with repair processes after ionising radiation damage in living organisms. Also exogenous ATP can play a central part in radioprotection. This paper considers interaction between the multifactorial roles of ATP in radioprotection and metabolic provision for repair processes, which can depend on its physiological regulatory function as a neuromodulator via cell membrane receptors. It is hypothesised that all these complex functions reflect an adaptive defence mechanism, against radiation insults, in which ATP plays a pivotal role to maintain homeostasis. PMID- 2204793 TI - [Emergencies in children]. PMID- 2204792 TI - Major histocompatibility antigens and spontaneous abortion: an evolutionary perspective. AB - Maternal-fetal histocompatibility as a consequence of sharing of MHC antigens between males and females may result in an increased incidence of spontaneous abortion. We propose that such a response may be of evolutionary significance in inbred populations where partners that are similar at MHC loci also are likely to share deleterious recessive alleles due to common descent. In this scenario, spontaneous abortion is regarded as an adaptive response on behalf of the mother, who terminates at an early stage her investment in an offspring which would likely be of low reproductive value if carried to term. PMID- 2204794 TI - Braxton Hicks vs. preterm labor. PMID- 2204796 TI - [Bone resorption and cytokines: the role of IL-1 beta, TNF and lymphotoxin]. AB - Tumor necrosis factor (TNF) and interleukin-1 (IL-1) are soluble factors that play a pivotal role in acute and chronic inflammation. TNF is a 17 Kda protein mainly released by monocytes and macrophages and is a common mediator of toxic shock, cachexia and tumor necrosis. IL-1 was first described as a lymphocyte activating factor and it was then discovered that IL-1 has a number of other biological activities and that there are at least two major types of IL-1 (alpha and beta) which bind to the same receptor. Recently it has been shown that TNF and IL-1 beta have an important role in bone resorption. PMID- 2204795 TI - [Neutrophil function and microbial associations in rapidly progressing periodontitis and chronic periodontitis in the adult]. AB - Our study was focused on the functional characteristics of neutrophil leukocytes (PMN) and the subgingival microflora in two different forms of periodontal disease: 1) adult periodontitis (AP); 2) rapidly progressive periodontitis (RPP). Our study dealt with the functional characteristics of neutrophil leukocytes in the gingival fluid and in the peripheral blood. These were found markedly reduced in the RPP group, while, in the AP group, they were comparable to those of a healthy control group. No difference between local and systemic values was detected. Moreover, some samples of subgingival plaque were taken from two groups of patients, affected by AP and RPP respectively. The above samples showed a predominance of Gram-negative flora over Gram-positive flora, and of anaerobic flora over the aerobic one, and the predominance of specific pathogens in each of the two forms of periodontal disease. The subgingival plaque samples taken at the end of the periodontal treatment from five out of ten patients affected by RPP showed inverse ratios, as well as the absence of the previously detected pathogens. The findings underline the relevance of tests of leukocytes functionality and that of microbiological analysis to allow correct diagnosis of dubious forms of periodontal disease and the checking of the posttreatment results. PMID- 2204797 TI - [Oral hairy leukoplakia in patients with HIV infection]. AB - Oral hairy leukoplakia is a new clinicopathological entity. Little is known about its etiology, pathogenesis and natural history. It is considered a specific marker of HIV infection, although it has been also reported in HIV-negative patients. The etiology appears related to Epstein-Barr virus. Hairy leukoplakia has a characteristic clinical and histopathological aspect, but it is not specific. Because hairy leukoplakia may be easily confused with other lesions of the tongue, the dentist should be very careful in making the final diagnosis. Hairy leukoplakia is usually asymptomatic and treatment is not necessary. In cases of extensive lesions or psychological intolerance of the patient, useful drugs are acyclovir and vitamin A derivatives. PMID- 2204798 TI - [The role of the dentist in the pre- and postoperative treatment of the cancer patient]. AB - The importance of an early diagnosis in neoplastic pathologies of the oral cavity is now universally recognised and accepted, and dental treatment in this field requires particular care and preparation. Having identified the suspected lesions, it is necessary to eliminate those conditions which might favour the onset of neoplasia in the oral cavity, and then follow the patient during the pre and post-radiotherapeutic stages. Dentistry is also responsible for following and carrying out the prosthetic recovery of patients undergoing radical jaw surgery, in order to enable them to return to normal day-to-day and working life in esthetic and functional terms. PMID- 2204800 TI - [Chondrosarcoma of the jaws. A review of the literature and the diagnostic and therapeutic considerations]. AB - Following a general introduction, the paper reports a case of rapidly developing chondrosarcoma of the upper jaw. The biological behaviour of this rare form of neoplasia at a maxillofacial level is briefly discussed together with the outcome. PMID- 2204799 TI - [Multiple lipomatosis or Launois-Bensaude disease. Technics for surgical treatment in our clinical experience]. AB - Only 200 cases of this extremely rare disease of unknown etiology have been reported in the literature. The paper examines the various surgical techniques and describes two cases operated by the authors. PMID- 2204802 TI - [Effects of estrogen on pancreatic endocrine function after major resection of a fibrotic pancreas caused by ligation of the pancreatic ducts in dogs]. AB - Following major resection of a fibrotic pancreas and reconstruction of the major pancreatic duct four weeks after ligation of both major and minor pancreatic ducts in dogs, effects of estrogen administration on endocrine function of the remnant pancreas were investigated. Development of diabetes mellitus after major resection of the pancreas was markedly prevented with estrogen administration. Glucose tolerance, insulin secretion and morphology of islet cells were kept in better condition with estrogen administration than without it and in particular degeneration of B-cells was found markedly inhibited by estrogen administration. The study revealed that the endocrine function following major resection of the fibrotic pancreas caused by ligation of the pancreatic ducts and duct reconstruction was maintained well by estrogen administration, which prevented the development of diabetes mellitus. PMID- 2204801 TI - [A clinicopathological study of mucus producing bile duct carcinoma]. AB - Bile duct carcinoma, which produces clinically recognizable mucus, was defined as "mucus producing bile duct carcinoma", and clinicopathological study was carried out in 7 cases of bile duct carcinoma suitable for the definition. All the tumors arose from the intrahepatic bile duct. There were no tumors arising from the extrahepatic bile duct. Superficially spreading mucosal infiltration of carcinoma was recognized in 6 cases out of 7, and accordingly distinct cholangiography after draining mucus through percutaneous transhepatic cholangio-drainage (PTCD) and percutaneous transhepatic cholangioscopy (PTCS) were indispensable for accurate diagnosis of the extent of carcinoma. The prognosis of patients with mucus producing bile duct carcinoma were almost satisfactory if rational operation had been performed according to accurate diagnosis. On the other hand, since mucus producing bile duct carcinoma frequently has a cystic lesion, the relation to biliary cystadenocarcinoma may become a subject of question. We advocate that biliary cystadenocarcinoma should be included in mucus producing bile duct carcinoma since biliary cystadenocarcinoma originally arises from the intrahepatic bile duct and very rarely from the extrahepatic bile duct. But now the concept of biliary cystadenocarcinoma is equivocal and further investigations will be requested. PMID- 2204803 TI - [Three cases of primary hyperparathyroidism associated with nonmedullary thyroid neoplasm]. AB - Among 18 surgical patients with primary hyperparathyroidism at this institution, 3 patients (16.7%) were found to have associated nonmedullary thyroid neoplasms. Histological examination of the parathyroid tumors revealed two to be parathyroid adenomas and the other to be parathyroid carcinoma. Histology of the thyroid neoplasms were papillary carcinoma, follicular carcinoma and follicular adenoma, respectively. Therefore, in the diagnosis of primary hyperparathyroidism, it is necessary to take into consideration association with not only medullary thyroid carcinoma, but nonmedullary thyroid neoplasms as well. PMID- 2204804 TI - Farnesyl cysteine C-terminal methyltransferase activity is dependent upon the STE14 gene product in Saccharomyces cerevisiae. AB - Membrane extracts of sterile Saccharomyces cerevisiae strains containing the a specific ste14 mutation lack a farnesyl cysteine C-terminal carboxyl methyltransferase activity that is present in wild-type a and alpha cells. Other a-specific sterile strains with ste6 and ste16 mutations also have wild-type levels of the farnesyl cysteine carboxyl methyltransferase activity. This enzyme activity, detected by using a synthetic peptide sequence based on the C-terminus of a ras protein, may be responsible not only for the essential methylation of the farnesyl cysteine residue of a mating factor, but also for the methylation of yeast RAS1 and RAS2 proteins and possibly other polypeptides with similar C terminal structures. We demonstrate that the farnesylation of the cysteine residue in the peptide is required for the methyltransferase activity, suggesting that methyl esterification follows the lipidation reaction in the cell. To show that the loss of methyltransferase activity is a direct result of the ste14 mutation, we transformed ste14 mutant cells with a plasmid complementing the mating defect of this strain and found that active enzyme was produced. Finally, we demonstrated that a similar transformation of cells possessing the wild-type STE14 gene resulted in sixfold overproduction of the enzyme. Although more complicated possibilities cannot be ruled out, these results suggest that STE14 is a candidate for the structural gene for a methyltransferase involved in the formation of isoprenylated cysteine alpha-methyl ester C-terminal structures. PMID- 2204805 TI - Mutations that define the optimal half-site for binding yeast GCN4 activator protein and identify an ATF/CREB-like repressor that recognizes similar DNA sites. AB - The yeast GCN4 transcriptional activator protein binds as a dimer to a dyad symmetric sequence, indicative of a protein-DNA complex in which two protein monomers interact with adjacent half-sites. However, the optimal GCN4 recognition site, ATGA(C/G)TCAT, is inherently asymmetric because it contains an odd number of base pairs and because mutation of the central C.G base pair strongly reduces specific DNA binding. From this asymmetry, we suggested previously that GCN4 interacts with nonequivalent and possibly overlapping half-sites (ATGAC and ATGAG) that have different affinities. Here, we examine the nature of GCN4 half sites by creating symmetrical derivatives of the optimal GCN4 binding sequence that delete or insert a single base pair at the center of the site. In vitro, GCN4 bound efficiently to the sequence ATGACGTCAT, whereas it failed to bind to ATGAGCTCAT or ATGATCAT. These observations strongly suggest that (i) GCN4 specifically recognizes the central base pair, (ii) the optimal half-site for GCN4 binding is ATGAC, not ATGAG, and (iii) GCN4 is a surprisingly flexible protein that can accommodate the insertion of a single base pair in the center of its compact binding site. The ATGACGTCAT sequence strongly resembles sites bound by the yeast and mammalian ATF/CREB family of proteins, suggesting that GCN4 and the ATF/CREB proteins recognize similar half-sites but have different spacing requirements. Unexpectedly, in the context of the his3 promoter, the ATGACGTCAT derivative reduced transcription below the basal level in a GCN4-independent manner, presumably reflecting DNA binding by a distinct ATF/CREB-like repressor protein. In other promoter contexts, however, the same site acted as a weak upstream activating sequence. PMID- 2204806 TI - Multiple positive and negative cis-acting elements mediate induced arginase (CAR1) gene expression in Saccharomyces cerevisiae. AB - Expression of the arginase (CAR1) gene in Saccharomyces cerevisiae is induced by arginine or its analog homoarginine. Induction has been previously shown to require a negatively acting upstream repression sequence, which maintains expression of the gene at a low level in the absence of inducer. The objective of this work was to identify the cis-acting elements responsible for CAR1 transcriptional activation and response to inducer. We identified three upstream activation sequences (UASs) that support transcriptional activation in a heterologous expression vector. Two of these UAS elements function in the absence of inducer, whereas the third functions only when inducer is present. One of the inducer-independent UAS elements exhibits significant homology to the Sp1 factor binding sites identified in simian virus 40 and various mammalian genes. PMID- 2204807 TI - A transcriptionally active form of TFIIIC is modified in poliovirus-infected HeLa cells. AB - In HeLa cells, RNA polymerase III (pol III)-mediated transcription is severely inhibited by poliovirus infection. This inhibition is due primarily to the reduction in transcriptional activity of the pol III transcription factor TFIIIC in poliovirus-infected cells. However, the specific binding of TFIIIC to the VAI gene B-box sequence, as assayed by DNase I footprinting, is not altered by poliovirus infection. We have used gel retardation analysis to analyze TFIIIC-DNA complexes formed in nuclear extracts prepared from mock- and poliovirus-infected cells. In mock-infected cell extracts, two closely migrating TFIIIC-containing complexes, complexes I and II, were detected in the gel retardation assay. The slower migrating complex, complex I, was absent in poliovirus-infected cell extracts, and an increase occurred in the intensity of the faster-migrating complex (complex II). Also, in poliovirus-infected cell extracts, a new, rapidly migrating complex, complex III, was formed. Complex III may have been the result of limited proteolysis of complex I or II. These changes in TFIIIC-containing complexes in poliovirus-infected cell extracts correlated kinetically with the decrease in TFIIIC transcriptional activity. Complexes I, II, and III were chromatographically separated; only complex I was transcriptionally active and specifically restored pol III transcription when added to poliovirus-infected cell extracts. Acid phosphatase treatment partially converted complex I to complex II but did not affect the binding of complex II or III. Dephosphorylation and limited proteolysis of TFIIIC are discussed as possible mechanisms for the inhibition of pol III-mediated transcription by poliovirus. PMID- 2204808 TI - REB1, a yeast DNA-binding protein with many targets, is essential for growth and bears some resemblance to the oncogene myb. AB - REB1 is a DNA-binding protein that recognizes sites within both the enhancer and the promoter of rRNA transcription as well as upstream of many genes transcribed by RNA polymerase II. We report here the cloning of the gene for REB1 by screening a yeast genomic lambda gt11 library with specific oligonucleotides containing the REB1 binding site consensus sequence. The REB1 gene was sequenced, revealing an open reading frame encoding 809 amino acids. The predicted protein was highly hydrophilic, with numerous OH-containing amino acids and glutamines, features common to many of the general DNA-binding proteins of Saccharomyces cerevisiae, such as ABF1, RAP1, GCN4, and HSF1. There was some homology between a portion of REB1 and the DNA-binding domain of the oncogene myb. REB1 is an essential gene that maps on chromosome II. However, the physiological role that it plays in the cell has yet to be established. PMID- 2204809 TI - Ribosomal protein L30 is dispensable in the yeast Saccharomyces cerevisiae. AB - In the yeast Saccharomyces cerevisiae, L30 is one of many ribosomal proteins that is encoded by two functional genes. We have cloned and sequenced RPL30B, which shows strong homology to RPL30A. Use of mRNA as a template for a polymerase chain reaction demonstrated that RPL30B contains an intron in its 5' untranslated region. This intron has an unusual 5' splice site, C/GUAUGU. The genomic copies of RPL30A and RPL30B were disrupted by homologous recombination. Growth rates, primer extension, and two-dimensional ribosomal protein analyses of these disruption mutants suggested that RPL30A is responsible for the majority of L30 production. Surprisingly, meiosis of a diploid strain carrying one disrupted RPL30A and one disrupted RPL30B yielded four viable spores. Ribosomes from haploid cells carrying both disrupted genes had no detectable L30, yet such cells grew with a doubling time only 30% longer than that of wild-type cells. Furthermore, depletion of L30 did not alter the ratio of 60S to 40S ribosomal subunits, suggesting that there is no serious effect on the assembly of 60S subunits. Polysome profiles, however, suggest that the absence of L30 leads to the formation of stalled translation initiation complexes. PMID- 2204810 TI - cis- and trans-acting regulatory elements of the yeast URA3 promoter. AB - Expression of the yeast pyrimidine biosynthetic gene, URA3, is induced three- to fivefold in response to uracil starvation, and this regulation is mediated by the transcriptional activator PPR1 (pyrimidine pathway regulator 1). In this study, we have analyzed the regulatory elements of the URA3 promoter by DNase I footprinting, using partially purified yeast cell extracts, by deletion mutagenesis, and by 5'-end mapping of RNA transcripts. Two DNA-binding activities have been detected, and at least four distinct cis-acting regions have been identified. A region rich in poly(dA-dT) serves as an upstream promoter element necessary for the basal level of URA3 expression. A 16-base-pair sequence with dyad symmetry acts acts as a uracil-controlled upstream activating site (UASURA) and shows a specific binding only with cell extracts from strains overproducing PPR1. This in vitro binding does not require dihydroorotic acid, the physiological inducer of URA3. The TATA region appears to be composed of two functionally distinct (constitutive and regulatory) elements. Two G + A-rich regions surrounding this TATA box bind an unidentified factor called GA-binding factor. The 5' copy, GA1, is involved in PPR1 induction and overlaps the constitutive TATA region. The 3' region, GA2, is necessary for maximal expression. Neither of these GA sequences acts as a UAS in a CYC1-lacZ context. The promoters of the unlinked but coordinately regulated URA1 and URA4 genes contain highly conserved copies of the UASURA sequence, which prompted us to investigate the effects of many point mutations within this UASURA sequence on PPR1-dependent binding. In this way, we have identified the most important residues of this binding site and found that a nonsymmetrical change of these bases is sufficient to prevent the specific binding and to suppress the UASURA activity in vivo. In addition, we showed that UASURA contains a constitutive activating element which can stimulate transcription from a heterologous promoter independently of dihydroorotic acid and PPR1. PMID- 2204812 TI - Phenotypic consequences of tubulin overproduction in Saccharomyces cerevisiae: differences between alpha-tubulin and beta-tubulin. AB - Overexpression of alpha- and beta-tubulin genes in Saccharomyces cerevisiae, separately or together, leads to accumulation of large excesses of each of the polypeptides and arrest of cell division. However, other consequences of overexpression of these genes differ in several ways. As shown previously (D. Burke, P. Gasdaska, and L. Hartwell, Mol. Cell. Biol. 9:1049-1059, 1989), overexpression of beta-tubulin leads, at early times, to loss of microtubule structures and loss of viability. Eventually, the excess beta-tubulin forms abnormal structures. We show here that, in contrast, overexpression of alpha tubulin led to none of these phenotypes and in fact could suppress each of the phenotypes associated with beta-tubulin accumulation. Truncated forms of beta tubulin that were not competent to carry out microtubule functions also failed to elicit the beta-tubulin-specific phenotypes when overexpressed. The data support the hypothesis that beta-tubulin in excess over alpha-tubulin is uniquely toxic, perhaps because it interferes with normal microtubule assembly. PMID- 2204811 TI - Regulation of tubulin levels and microtubule assembly in Saccharomyces cerevisiae: consequences of altered tubulin gene copy number. AB - Microtubule organization in the cytoplasm is in part a function of the number and length of the assembled polymers. The intracellular concentration of tubulin could specify those parameters. Saccharomyces cerevisiae strains constructed with moderately decreased or increased copy numbers of tubulin genes provide an opportunity to study the cellular response to a steady-state change in tubulin concentration. We found no evidence of a mechanism for adjusting tubulin concentrations upward from a deficit, nor did we find a need for such a mechanism: cells with no more than 50% of the wild-type tubulin level were normal with respect to a series of microtubule-dependent properties. Strains with increased copies of both alpha- and beta-tubulin genes, or of alpha-tubulin genes alone, apparently did down regulate their tubulin levels. As a result, they contained greater than normal concentrations of tubulin but much less than predicted from the increase in gene number. Some of this down regulation occurred at the level of protein. These strains were also phenotypically normal. Cells could contain excess alpha-tubulin protein without detectable consequences, but perturbations resulting in excess beta-tubulin genes may have affected microtubule-dependent functions. All of the observed regulation of levels of tubulin can be explained as a response to toxicity associated with excess tubulin proteins, especially if beta-tubulin is much more toxic than alpha-tubulin. PMID- 2204813 TI - The leucine zipper of c-Myc is required for full inhibition of erythroleukemia differentiation. AB - The leucine zipper motif has been observed in a number of proteins thought to function as eucaryotic transcription factors. Mutation of the leucine zipper interferes with protein dimerization and DNA binding. We examined the effect of point mutations in the leucine zipper of c-Myc on its ability to dimerize in vitro and to inhibit Friend murine erythroleukemia (F-MEL) differentiation. Glutaraldehyde cross-linking studies failed to provide evidence for homodimerization of in vitro-synthesized c-Myc protein, although it was readily demonstrated for c-Jun. Nevertheless, whereas transfected wild-type c-myc sequences strongly inhibited F-MEL differentiation, those with single or multiple mutations in the leucine zipper were only partially effective in this regard. Since the leucine zipper domain of c-Myc is essential for its cooperative effect in ras oncogene-mediated transformation, this study emphasizes the close relationship that exists between transformation and hematopoietic commitment and differentiation. c-Myc may produce its effects on F-MEL differentiation through leucine zipper-mediated heterodimeric associations rather than homodimeric ones. PMID- 2204814 TI - N-myc expression switched off and class I human leukocyte antigen expression switched on after somatic cell fusion of neuroblastoma cells. AB - Neuroblastomas often show amplification and high expression of the N-myc oncogene. N-myc expression could be explained as a consequence of gene amplification, but an alternative possibility is that expression primarily results from the inactivation or loss of some factor that normally represses the N-myc gene. To test this idea, we fused N-myc-overexpressing neuroblastoma cell lines with lines that do not express N-myc. In the resulting hybrids, N-myc expression turned out to be switched off, although amplified N-myc copies were still present. This suggests that N-myc overexpression in neuroblastomas results, at least in part, from the inactivation of a suppressor gene that is present in normal cells. In rat neuroblastomas, it has been found that N-myc can switch off class I major histocompatibility complex (MHC) expression. Therefore, we analyzed in our hybrid cells whether suppression of N-myc results in reexpression of human class I MHC genes. Because this was found to be the case, the picture emerges of a hierarchic pathway that connects a putative tumor-suppressor gene with the expression of N-myc and consequently of class I MHC, thus affecting the potential immunogenic properties of neuroblastomas. PMID- 2204815 TI - The promoter of the human interleukin-2 gene contains two octamer-binding sites and is partially activated by the expression of Oct-2. AB - The gene encoding interleukin-2 (IL-2) contains a sequence 52 to 326 nucleotides upstream of its transcriptional initiation site that promotes transcription in T cells that have been activated by costimulation with tetradecanoyl phorbol myristyl acetate (TPA) and phytohemagglutinin (PHA). We found that the ubiquitous transcription factor, Oct-1, bound to two previously identified motifs within the human IL-2 enhancer, centered at nucleotides -74 and -251. Each site in the IL-2 enhancer that bound Oct-1 in vitro was also required to achieve a maximal transcriptional response to TPA plus PHA in vivo. Point mutations within either the proximal or distal octamer sequences reduced the response of the enhancer to activation by 54 and 34%, respectively. Because the murine T-cell line EL4 constitutively expresses Oct-2 and requires only TPA to induce transcription of the IL-2 gene, the effect of Oct-2 expression on activation of the IL-2 promoter in Jurkat T cells was determined. Expression of Oct-2 potentiated transcription 13-fold in response to TPA plus PHA and permitted the enhancer to respond to the single stimulus of TPA. Therefore, both the signal requirements and the magnitude of the transcription response of the IL-2 promoter can be modulated by Oct-2. PMID- 2204816 TI - The mouse c-rel protein has an N-terminal regulatory domain and a C-terminal transcriptional transactivation domain. AB - We have shown that the murine c-rel protein can act as a transcriptional transactivator in both yeast and mammalian cells. Fusion proteins generated by linking rel sequences to the DNA-binding domain of the yeast transcriptional activator GAL4 activate transcription from a reporter gene linked in cis to a GAL4 binding site. The full-length mouse c-rel protein (588 amino acids long) is a poor transactivator; however, the C-terminal portion of the protein between amino acid residues 403 to 568 is a potent transcriptional transactivator. Deletion of the N-terminal half of the c-rel protein augments its transactivation function. We propose that c-rel protein has an N-terminal regulatory domain and a C-terminal transactivation domain which together modulate its function as a transcriptional transactivator. PMID- 2204817 TI - Cell type-specific mechanisms of regulating expression of the ornithine decarboxylase gene after growth stimulation. AB - Ornithine decarboxylase (ODC) mRNA is strongly induced by mitogenic activation of resting Swiss 3T3 fibroblasts and T lymphocytes. Nuclear run-on analysis revealed a low level of nascent transcripts in resting fibroblasts that was elevated upon activation. In contrast, there was a high level of transcription across the entire ODC gene in resting T cells, which remained unchanged upon activation. The stability of the mature ODC message was found to be unaffected by mitogenic stimulation. These results indicate that ODC mRNA levels are regulated transcriptionally in Swiss 3T3 cells and posttranscriptionally within the nucleus of T lymphocytes in response to mitogenic stimuli. In this unique situation, the mitogenic induction of a single gene, ODC, is regulated by two very distinct, cell-specific mechanisms. PMID- 2204820 TI - [Pathology of Crohn disease in children]. AB - Incidence, macroscopic and histological appearance, and systemic manifestation of Crohn's disease in children are discussed. The main criteria for the differentiation between idiopathic inflammatory bowel disease (Crohn's disease and ulcerative colitis) and acute self-limited colitis (infectious colitis) of the intestinal tract are reviewed. Finally, a description of the morphology of precancerous changes and their clinical implications in Crohn's disease (and ulcerative colitis) is given. PMID- 2204819 TI - The DNA damage-inducible gene DIN1 of Saccharomyces cerevisiae encodes a regulatory subunit of ribonucleotide reductase and is identical to RNR3. AB - The sequence of the DIN1 gene of Saccharomyces cerevisiae is identical to RNR3, a gene encoding a DNA damage-inducible regulatory subunit of ribonucleotide reductase. Two sequence elements located upstream of DIN1 (RNR3) are homologous to putative DNA damage regulatory elements in the promoter of the reductase catalytic subunit gene, RNR2. The transcript start sites for DIN1(RNR3) have been localized, and induction by different agents has been compared with other DNA damage-regulated genes. PMID- 2204818 TI - Increased expression and DNA-binding activity of transcription factor Sp1 in doxorubicin-resistant HL-60 leukemia cells. AB - The processes responsible for the multidrug-resistant (Mdr) phenotype in Adriamycin (doxorubicin)-resistant HL-60 leukemia cells (HL-60/AR) are not defined. Since enhanced transcription of resistance-related proteins is associated with Mdr cells, we sought to determine whether changes in the expression of specific transcription factors were a feature characteristic of the Mdr process. Nuclear extracts were prepared from wild-type and resistant cells and compared for their ability to bind DNA consensus sequences for the transcription factors Sp1 and NF kappa B contained in the 5' long terminal repeat region of human immunodeficiency virus type 1. Southwestern (DNA-protein) blots showed a family of DNA-binding proteins of 105 kilodaltons (kDa) that were present only in HL-60/AR cells. Competitive gel shift assays indicated that these factors were related to transcription factor Sp1, and immunoblotting with an Sp1 antibody identified this factor as Sp1. DNase footprinting of the promoter region in the human immunodeficiency virus type 1 5' long terminal repeat showed that protection occurred at two Sp1 sites as well as two NF kappa B sites and the trans-acting region with nuclear extracts only from resistant cells. Preliminary evidence also suggests that phosphorylation may play a negative regulatory role in the activity of Sp1, since calf intestine alkaline phosphatase stimulated the DNA-binding activity of Sp1 in vitro. These results indicate that HL-60/AR cells contain an abundance of DNA-binding proteins, particularly Sp1, which probably interact with other cis-acting regulatory proteins in a cooperative manner. PMID- 2204821 TI - [Diagnosis and treatment of celiac disease--what is the status in 1990?]. AB - Summarizing the development of experiences and discussions of the last 20 years, a working group of the ESPGAN has recently updated the criteria of diagnosis of coeliac disease. The reliable finding of the initial typical mucosal lesion in the untreated patient is a hallmark of the disease and, if followed by an unequivocal clinical response to a gluten free diet, can be considered as final evidence for the diagnosis. Gluten challenges should be limited to cases without this evidence. High levels of antigliadin- and antireticulin- or or antiendomysium antibodies are supportive for the diagnosis but cannot substitute biopsy proof of the disease. The importance of a very long term strict gluten free diet in coeliac disease is established by recent evidence showing that in such cases there is no increased risk of malignancy. PMID- 2204822 TI - [Pre- and postnatal diagnosis of organoacidopathies]. AB - Organoacidopathies are the most common life-threatening inborn errors of metabolism presenting acutely in the neonatal period. Early diagnosis rests on a high degree of suspicion. Clinical and laboratory findings are often nonspecific and can be misinterpreted. We present an algorithm for a quick and comprehensive diagnosis of these disorders using commonly available parameters. Different methods for the prenatal diagnosis of organoacidopathies are discussed and our experience with over 150 cases presented. The method of choice is the precise quantification of elevated levels of metabolites in amniotic fluid obtained by amniocentesis at 12-18 weeks of pregnancy. Quantification is best done by stable isotope dilution analysis with the addition of the labelled metabolite to the amniotic fluid. A positive prenatal diagnosis allows a decision of the family for a termination of pregnancy or the immediate institution of therapy after birth. The conduction of a prenatal diagnosis requires the knowledge of the exact diagnosis of a previously affected child. PMID- 2204823 TI - DNA photolyases: physical properties, action mechanism, and roles in dark repair. AB - DNA photolyases catalyze the light-dependent repair of cis,syn-cyclobutane dipyrimidines (pyrimidine dimers). Although the phenomenon of enzymatic photoreactivation was first described 40 years ago and photolyases were the first enzymes shown unequivocally to effect DNA repair, it has only been in the last 8 years that sufficient quantities of the enzymes have been purified to permit detailed studies of their physical properties, identification of their intrinsic chromophores, and elucidation of the mechanisms of dimer recognition and photolysis. In addition several of the genes encoding these enzymes have now been cloned and sequenced. These studies have revealed remarkable functional and structural conservation among these evolutionarily ancient enzymes and have identified a new role for photolyases in dark-repair processes which has implications for the mechanism of nucleotide excision repair in both prokaryotes and eukaryotes. PMID- 2204824 TI - Structures and functions of DNA glycosylases. PMID- 2204825 TI - Structure and function of the (A)BC excinuclease of Escherichia coli. AB - (A)BC excinuclease is the enzymatic activity resulting from the mixture of E. coli UvrA, UvrB and UvrC proteins with damaged DNA. This is a functional definition as new evidence suggests that the three proteins never associate in a ternary complex. The UvrA subunit associates with the UvrB subunit in the form of an A2B1 complex which, guided by UvrA's affinity for damaged DNA binds to a lesion in DNA and delivers the UvrB subunit to the damaged site. The UvrB-damaged DNA complex is extremely stable (t1/2 congruent to 100 min). The UvrC subunit, which has no specific affinity for damaged DNA, recognizes the UvrB-DNA complex with high specificity and the protein complex consisting of UvrB and UvrC proteins makes two incisions, the 8th phosphodiester bond 5' and the 5th phosphodiester bond 3' to the damaged nucleotide. (A)BC excinuclease recognizes DNA damage ranging from AP sites and thymine glycols to pyrimidine dimers, and the adducts of psoralen, cisplatinum, mitomycin C, 4-nitroquinoline oxide and interstrand crosslinks. PMID- 2204826 TI - Use of in vivo and in vitro assays for the characterization of mammalian excision repair and isolation of repair proteins. AB - Elucidation of the molecular mechanism of mammalian nucleotide excision repair requires the availability of purified proteins, DNA substrates with defined lesions and suitable repair assays. Repair assays introduced in recent years vary from testing individual steps and successions of steps in vitro to systems that closely reflect the entire process in vivo. In the first part of this review, an in vivo microinjection system is discussed. The second part of the article reviews an in vitro system for study of repair synthesis promoted by cell extracts. Both systems can be utilized as assays during the purification of protein factors that complement repair-defective xeroderma pigmentosum cells. The effect of purified repair proteins from other organisms on mammalian repair is also considered. PMID- 2204827 TI - Eukaryotic DNA ligases. AB - Recent studies on eukaryotic DNA ligases are briefly reviewed. The two distinguishable enzymes from mammalian cells, DNA ligase I and DNA ligase II, have been purified to homogeneity and characterized biochemically. Two distinct DNA ligases have also been identified in Drosophila melanogaster embryos. The genes encoding DNA ligases from Schizosaccharomyces pombe, Saccharomyces cerevisiae and vaccinia virus have been cloned and sequenced. These 3 proteins exhibit about 30% amino acid sequence identity; the 2 yeast enzymes share 53% amino acid sequence identity or conserved changes. Altered DNA ligase I activity has been found in cell lines from patients with Bloom's syndrome, although a causal link between the enzyme deficiency and the disease has not yet been proven. PMID- 2204828 TI - Characterization, cloning and host-protective activity of a 30-kilodalton glycoprotein secreted by the parasitic stages of Trichostrongylus colubriformis. AB - The helminth Trichostrongylus colubriformis is a parasitic nematode infecting the small intestine of sheep. We report the isolation and characterization of a 30 kDa glycoprotein capable of partially protecting guinea-pigs against the parasite. This glycoprotein is secreted by the L4 and adult parasitic stages of the worm. The sequence of three separate cDNA clones predicts the polypeptide to be about 15 kDa, with four N-linked carbohydrate chains and an internal disulphide bond. The clones also indicate the existence of sequence variability in this antigen. Limited sequence homology to a porcine intestinal peptide suggests an influence on host gut physiology. PMID- 2204829 TI - A family of glycolipid linked proteins in Eimeria tenella. AB - A number of proteins in Eimeria tenella are shown to possess a carbohydrate similar to that found on the carboxyl terminus of the variant surface glycoprotein from Trypanosoma brucei. In trypanosomes, this carbohydrate is part of a glycolipid structure responsible for membrane attachment. In common with the variant surface glycoprotein and with other glycolipid linked proteins, the E. tenella proteins were shown to be hydrophobic. Treatment with a crude lipase preparation from T. brucei modifies these proteins to a water-soluble form. PMID- 2204830 TI - Primary structure of Trypanosoma cruzi small-subunit ribosomal RNA coding region: comparison with other trypanosomatids. AB - A Trypanosoma cruzi small subunit ribosomal RNA gene was sequenced from genomic recombinant plasmid clones. The assigned coding region was 2319 bp, the longest SSU rRNA gene described to date. On the basis of comparisons with published sequences from Crithidia fasciculata, Trypanosoma brucei, and Leishmania donovani, we conclude that the extra nucleotides in the T. cruzi gene occur in highly variable regions of rRNA genes. A phylogenetic analysis was performed with the SSU rRNA sequences from these four trypanosomatids and from Euglena gracilis as an outgroup. The Leishmania and Crithidia sequences were remarkably similar to each other (not separable statistically). Given the standard errors associated with the branching order of the two Trypanosoma species and the Leishmania Crithidia branch, the actual topology cannot be unequivocally determined using only the ribosomal sequences analyzed here. PMID- 2204831 TI - Cytochrome P-450 activity in malarial parasites and its possible relationship to chloroquine resistance. AB - Cytochrome P-450-dependent enzyme activities have been determined in malarial parasites. Both Plasmodium berghei and Plasmodium falciparum parasites exhibited activity and these activities were greater in chloroquine resistant parasites than in sensitive strains. This enzyme activity could be induced by phenobarbitone and inhibited by specific inhibitors of the cytochrome P-450 family of enzymes. The significance of these observations in parasite drug resistance is discussed. PMID- 2204833 TI - Regions of an Eimeria tenella antigen contain sequences which are conserved in circumsporozoite proteins from Plasmodium spp. and which are related to the thrombospondin gene family. AB - Coccidiosis, caused by Eimeria spp., is a major disease of economic importance to the poultry industry. The cloning and characterisation of genes coding for antigens of those species infecting chickens is an initial step in the identification of protective antigens suitable for the development of a genetically engineered vaccine. This report describes the molecular characterisation of an antigen of E. tenella produced by the recombinant lambda amp3 bacteriophage EtHL6. Three native polypeptides corresponding to the EtHL6 antigen, with sizes between 110 and 94 kDa, have been identified on both sporozoites and second generation merozoites of E. tenella by mouse antisera raised against the EtHL6 fusion protein. The DNA insert is a 722-bp EcoRI fragment encoding a polypeptide comprising three tandem blocks of amino acids which are highly homologous to each other. Each region, A, B and C, contains a strongly hydrophilic domain and two pairs of cysteine residues. Computer analysis has identified similarities with a group of proteins which include the circumsporozoite antigen and thrombospondin-related anonymous protein (TRAP) of malaria parasites, human thrombospondin, mouse properdin and the terminal components of the complement pathway. PMID- 2204832 TI - Expression, purification, biochemical characterization and inhibition of recombinant Plasmodium falciparum aldolase. AB - The energy metabolism of the blood stage form of the human malaria parasite Plasmodium falciparum is adapted to the host cell. Like erythrocytes, P. falciparum merozoites lack a functional citric acid cycle. Generation of ATP depends therefore fully on the glycolytic pathway. Aldolase is a key enzyme of this pathway and a high degree of sequence diversity between parasite and host makes it a potential drug target. We have expressed the enzyme in its tetrameric form in Escherichia coli and the catalytic constants Vmax and Km of the recombinant enzyme correspond to the constants of parasite-derived aldolase. Rabbit antibodies against the recombinant P. falciparum aldolase inhibit the natural enzyme and no cross-reaction with human aldolase is detectable. Both the recombinant and the natural protein bind to the cytosolic domain of the band 3 membrane protein in vitro. A 19-residue synthetic peptide corresponding to the sequence of the binding domain of band 3 is an inhibitor when included in the binding assay. In addition, this peptide inhibits the catalytic activity of recombinant P. falciparum aldolase when assayed in a buffer system devoid of anions such as chloride or phosphate. The band 3-derived peptides compete with the aldolase substrate fructose-1,6-diphosphate for binding, suggesting that both reagents have a high affinity for the substrate pocket. A similar sequence motif exists in P. falciparum actin II. A 19-residue peptide corresponding to this sequence is also an inhibitor which could suggest that the P. falciparum aldolase can associate with the cytoskeleton of the parasite or of the host. PMID- 2204834 TI - The gene for hypoxanthine phosphoribosyl transferase of Plasmodium falciparum complements a bacterial HPT mutation. AB - The enzyme hypoxanthine phosphoribosyl transferase of Plasmodium falciparum has been overexpressed in Escherichia coli. The protein was found to be active enzymatically. When the recombinant expression vector (pPfPRT2) was transformed and expressed in a Salmonella typhimurium mutant KP1684 (purE deoD hpt gpt), the active expressed protein complemented the hpt mutation in the bacteria. We discuss the practical value of this strain. Assays of the expressed protein in the mutant extract showed that the enzyme is able to use hypoxanthine, guanine and xanthine as substrates. A specificity study using the competitive inhibitor, 6-thioguanine, showed that of these hypoxanthine is the most favourable substrate. The biological significance of xanthine utilisation by the enzyme is discussed. PMID- 2204835 TI - Sequence conservation of a functional domain of erythrocyte binding antigen 175 in Plasmodium falciparum. PMID- 2204836 TI - Radiology of appendicitis impact of newer modalities. PMID- 2204837 TI - [A new concept of the role of the cerebellum in operative motor control and the shaping of motor automatism]. AB - A new theory of the cerebellum work is presented. It explains all the experimental data now accumulated. PMID- 2204838 TI - The role of ultrasound in the management of vein of Galen aneurysms in infancy. AB - Ultrasonography can be the key imaging modality for neonatal patients with vein of Galen aneurysms. Ultrasound can be used to diagnose the condition, monitor transtorcular embolization procedures, and follow-up these patients after embolization to assess the effectiveness of embolization and to check for complications. PMID- 2204839 TI - "Meningeal sign": a characteristic finding of meningiomas on contrast-enhanced MR images. AB - In meningiomas, a flat, contrast-enhancing, probably dural structure adjacent to the tumor can occasionally be observed on Gadolinium-DTPA enhanced MR images. This so called "meningeal sign" was evaluated with respect to the differential diagnosis of meningiomas in MR imaging. The study included 29 patients with intracranial meningiomas and 24 patients with non-meningeal brain tumors. In all meningiomas, MR studies included T2-weighted as well as unenhanced and Gadolinium DTPA-enhanced T1-weighted images. In all non-meningeal tumors, Gd-DTPA-enhanced MR images were available. All images were evaluated with respect to the presence of the "meningeal sign". In meningiomas, a "meningeal sign" was seen in 15/29 cases on Gadolinium-DTPA-enhanced images. No abnormalities corresponding to the areas of contrast enhancement were found on unenhanced T2- and T1-weighted MR images. In non-meningeal tumors only 2/24 cases showed a "meningeal sign". In conclusion, with a sensitivity of 52% and a specificity of 92%, the demonstration of the "meningeal sign" improved the differential diagnosis of intracranial meningiomas in contrast-enhanced MR imaging. PMID- 2204841 TI - Operative therapy in metastases and primary tumors of the spine. AB - Benign and primary malignant tumors of the spine require a ventral procedure to remove the tumor and to stabilize the spine. Experience in the last years has shown that sole laminectomy in children can no longer be recommended. An instrumentation of the spine to prevent kyphosis must be performed. The rate of pseudarthrosis was of course, high when the kyphosis was treated by an exclusive dorsal instrumentation. In patients with severe kyphosis a combined procedure with ventral and dorsal operation is necessary. Solitary metastases of cancer of the prostate, breast, and the thyroid gland show a better prognosis than metastases of cancer of the lung or the stomach. Thus metastases of the first group which also show a dependency on hormones, should be operated on by a ventral procedure, independent of the location of the tumor. In cases of multiple metastases and bad condition of the patient a ventral operation is not indicated. In these cases, a dorsal procedure with decompression and stabilization allows mobility of the patients until only few days before death. An implantation of instrumentations that include a transpedicular screwing can result in spreading of the tumor to the neighboring vertebrae. Therefore, this kind of operation should be the "ultima ratio". PMID- 2204842 TI - [Mechanical staplers in colorectal surgery]. AB - The results obtained with manual and mechanical suturing are compared on the basis of a review of a personal colon-rectum series. The advantages offered by staplers in this type of surgery are pointed out in agreement with reported data. PMID- 2204840 TI - Spinal functions in sensorimotor control of movements. AB - The transformation of sensory information to movement patterns in spinal interneuronal systems is far from just being a stereotyped reflex pattern. Information from the different sensory modalities (skin-, muscle, and joint receptors) is integrated at the interneuronal level and transformed into patterns of coordinated movements which are adapted to the current position and the phase of movement of a limb. In addition, spinal interneuronal systems are capable of generating rhythmic motor activities like locomotion or scratching without a sensory feed-back from the periphery and without a corresponding drive from supraspinal structures. The same interneuronal systems which are engaged in the reflexogenic control and generation of movements at the spinal level also convey information for the performance of supraspinally-induced, goal-directed ("voluntary") movements. The inherent convergence between descending and peripheral afferent information onto common interneuronal systems implies an improved coordination and adaptation of movements in dependence on the peripheral conditions. Disturbance of the supraspinal control of these interneuronal systems leads to an impairment of the transformation of sensory inputs into motor acts. Spasticity is probably partly caused by such a disturbed control of the transmission in the interneuronal systems. PMID- 2204843 TI - [Role of the conservative therapy in post-traumatic lesions of the spleen]. PMID- 2204844 TI - [Traumatic lesions of the spleen. Analysis of 35 cases]. AB - A retrospective review of all the traumatic splenic ruptures from 1974 to 1988 was performed. Thirty-five patients were treated with splenectomy: 24 were males and 11 women. Teenagers and young adults were the most affected age groups. The mechanisms of injuries were: road accidents (78.8%), falls (12.1%), aggression, autoaggression and iatrogenic mishap (3%). Eighty per cent of the patients had associated injuries. Authors suggest a decisional algorithm to precise preoperative diagnosis and to treat the patients correctly. Mortality was 11.4% and primarily due to associated injuries. PMID- 2204845 TI - [Current clinico-therapeutic trends in essential varicocele]. AB - The authors report their experience with the diagnosis and surgical correction of varicoceles in 20 patients. They stress the usefulness of the Doppler Ultrasound for the diagnosis of subclinical varicocele. PMID- 2204846 TI - Elements of grantsmanship: the process--the art. AB - Kelley and Gay give us an excellent overview of grantsmanship, noting among other things, that a good grant combines a methodical, systematic approach with creative imagination. These two linked articles will offer the beginning grant writer a good guide while providing the expert with some new perspectives to consider. PMID- 2204847 TI - The cocaine epidemic: treatment options for cocaine dependence. AB - Because the current cocaine epidemic has affected all levels of health care, the primary care provider is increasingly called on to identify and treat the consequences of cocaine abuse and dependence. Therefore, a thorough understanding of the recovery process can enable the clinician to devise a treatment plan that coincides with rehabilitation efforts. This article presents an analysis of current management strategies for cocaine abuse and dependence. By incorporating the use of a health care model that addresses the five domains of health- physical, psychological, family/social, personal and spiritual--the clinician is in a better position to treat and refer the individual and family afflicted with the disease of cocaine addiction. A description of contemporary ongoing research is included to highlight future directions and possible modifications in treatment approaches for psychoactive substance-use disorder. PMID- 2204848 TI - Post-traumatic stress disorder: an overview of three etiological variables, and psychopharmacologic treatment. AB - Three variables have been found to be important indicators in determining the development of post-traumatic stress disorder (PTSD): the pre-existing personality, the trauma involved and the individual's environment. The neurological impact of PTSD on the brain's pathways gives credence to psychopharmacologic treatment. Five treatment principles of PTSD are discussed as helpful models for treating this disorder. PMID- 2204849 TI - Pyomyoma associated with polymicrobial bacteremia and fatal septic shock: case report and review of the literature. AB - case of fatal septic shock due to pyomyoma (suppurative leiomyoma of the uterus) is reported. This unusual cause of sepsis and polymicrobial bacteremia should be rapidly identified because surgical therapy is essential for cure. Nine additional cases reported since 1945 are reviewed. Pyomyoma develops in association with either recent pregnancy or in postmenopausal patients who frequently have underlying vascular disease. The triad of: 1) bacteremia or sepsis; 2) leiomyoma uteri; and 3) no other apparent source of infection should suggest the diagnosis of pyomyoma. PMID- 2204850 TI - Vascular complications in women using the low steroid content combined oral contraceptive pills: case reports and review of the literature. PMID- 2204851 TI - Acute fatty liver of pregnancy. PMID- 2204852 TI - The 10 most-asked questions about reimbursement. Part I. PMID- 2204854 TI - Effect of intraocular aspiration of sodium hyaluronate on postoperative intraocular pressure. AB - A prospective, randomized, masked study was conducted to evaluate whether intraocular aspiration of sodium hyaluronate used in cataract surgery influenced postoperative intraocular pressure (IOP). Ninety-nine patients (105 eyes) underwent uncomplicated extracapsular extractions with posterior chamber intraocular lens implantation using 1% sodium hyaluronate (AMVISC). In 53 eyes, sodium hyaluronate was aspirated from the anterior chamber prior to wound closure. Sodium hyaluronate was left in the anterior chamber of 52 eyes. The IOP of 33 of the patients was measured 4 hours after surgery. No significant difference was found between the pressure in the eyes from which the sodium hyaluronate had been aspirated and the pressure in those from which it had not. The IOP of all the patients was measured on the first postoperative day. The mean 24 hours after surgery was 23.4 mm Hg in the aspirated eyes and 23.1 mm Hg in the not-aspirated group. Thirteen eyes in the aspirated group and 14 in the not aspirated group had pressures above 30 mm Hg during the first 24 hours after surgery. There were no significant differences in visual outcome, patient discomfort, corneal clarity, anterior chamber inflammation, or subsequent IOPs during 3 months postoperative examination. Aspiration of sodium hyaluronate at the end of cataract surgery does not appear to significantly reduce either the incidence or the degree of postoperative pressure elevations. PMID- 2204855 TI - Argon laser pretreatment in Nd: YAG iridotomy. AB - Argon laser pretreatment prior to Nd:YAG laser iridotomy may decrease the incidence of operative hemorrhage. In a prospective, randomized clinical trial involving 12 patients (24 eyes), one eye was randomly assigned treatment with the Nd:YAG laser alone, while the other eye was pretreated with argon laser photocoagulation immediately prior to Nd:YAG laser. Eight of the 12 eyes (67%) treated with Nd:YAG laser alone had operative hemorrhages; only 2 of the 12 (17%) pretreated eyes did. Thus, argon laser pretreatment significantly reduced the incidence of hemorrhage during Nd:YAG iridotomy (P = .012). PMID- 2204853 TI - Suture patterns and corneal graft rotation in the cadaver eye. AB - Torque and antitorque running sutures as described by Eisner are commonly used in penetrating keratoplasty. We tested the rotational effect of three different 16 bite running suture patterns on eight cadaver eyes, with the following results: (1) the torque pattern rotates the corneal graft counterclockwise by 0.7 +/- 0.1 mm at the wound or 11 degrees; (2) the antitorque pattern rotates the corneal graft clockwise by 0.7 +/- 0.1 mm at the wound or 11 degrees; (3) an intermediate "no torque" pattern, the bites of which form an isosceles triangle, produces no rotational effect. We recommend the use of a "no torque" pattern to minimize corneal graft rotation. PMID- 2204857 TI - Treatment of dysthyroid myopathy with adjustable suture recession. AB - Extraocular muscle recessions with adjustable sutures were performed on 32 muscles for diplopia secondary to dysthyroid-myopathy. Orthophoria in the primary position was achieved in 30 of the 32 (94%) 1 day after surgery. All remained orthophoric for at least 6 weeks. Of 20 patients followed for 6 months or more, 12 (60%) remained orthophoric for the full extent of their follow-up (6 months to 8 years), and another three (15%) were asymptomatic with prisms (3, 4, and 8 prism diopters). Thus, a total of 15 of 20 (75%) patients remained asymptomatic at least 6 months after surgery. PMID- 2204856 TI - Characteristics and behavior of eyelid carcinoma (basal cell, squamous cell sebaceous gland, and malignant melanoma). AB - Malignant tumors of the eyelid pose a serious threat because of their proximity to the globe, brain, and paranasal sinuses. We review the features of four common skin carcinomas involving the eyelid skin. Particular emphasis is given to their clinical presentation and to biologic behavior. Clinicians are encouraged to be aware of the clinical manifestations of these tumors, since early recognition and treatment result in the most cosmetically and functionally satisfactory results. An approach for rational treatment is presented. PMID- 2204858 TI - [Late results of primary suturing of the tendons of the flexors of 3-phalanx fingers in the first segment]. AB - The primary suture was put in 40 patients with 55 injuries of the tendons. The study of the long-term results of the treatment after putting the primary suture on 40 tendons of the flexors of the fingers of the hand has shown that in 21 patients who were put the sutures proposed by the authors there were excellent and good results in 90.4% of the cases. When classical sutures were put and the fingers were immobilized after the operation in 19 patients, the results were excellent and good in 84.3% of the cases, which was mostly at the expense of tenodesis effect in the distal interphalangeal joint. PMID- 2204859 TI - [A method of immobilization of patellar ligament after its suturing]. PMID- 2204860 TI - [Various prerequisites for performing the Sach-Weber operation in anterior instability of the shoulder joint]. AB - The authors present a preliminary analysis of the treatment of the patients with anterior instability of the shoulder joint who were given surgical treatment consisting in subcapital rotation osteotomy of the humerus and tendinous-capsular plasty of the anterior portion of the shoulder joint. The surgical technique and the indications for the operation are presented. PMID- 2204861 TI - [The value of the d-xylose loading test in the diagnosis of malabsorption syndromes]. AB - The test of d-xylose concentration in blood has been used for approximately two decades for the examination of the absorption. The authors compared in 261 cases the total d-xylose blood level with the histological picture of the small intestine. Good correlation was observed between the 2 examinations. The d-xylose loading was found to select with favorable efficacy the new cases of celiac disease, of 63 fresh diagnosed subtotal and total villus atrophy cases the blood level of 61 was under the 1,64 mmol/l limit. At the 3rd stage of partial villus atrophy the blood level was pathological in 17 new patients. The sensitivity of the examination was 92.2% in selection of the new cases. Significant differences were found between the new cases and patients with excess gliadin (0.929 +/- 0.44 mmol/l and 1383 +/- 0.052 mmol/l) with identical rate of duodenal tissue impairments. On this basis the significant decrease of d-xylose level (0.5-1 mmol/l) must be regarded as the sign of relapse in patients with excess gliadin. Giardia lamblia and slight villus impairment was found in the biopsy material of further 28 children. The d-xylose level was pathological in 14 of them. D-xylose absorption was pathological before treatment in each of the 13 patients with contaminated (Gram-negative aerobic bacteria) small intestinal syndrome. D-xylose test is a useful method in the diagnostics of conditions associated with malabsorption and completed with other techniques it provides means for the separation of conditions associated with the diffuse impairment of the small intestine. PMID- 2204862 TI - [Current interpretation of mosaicism]. AB - The development of cytogenetics and molecular genetics suggests a greater than expected importance of chromosomal, somatic and germ-line mosaicism. Mosaicism may cause varying expressivity of inherited diseases, aggregation of disorders regarded as "new mutations" in ostensibly healthy families, and neoplasia. Detection of latent parental mosaicism may enhance the prevention of abnormal offsprings. In clinical genetics this difficult problem may be solved from two approaches: 1. More thorough cytogenetic investigation of parents of children with chromosome aberrations. 2. Seeking for mild features of congenital disorders. The authors provide examples for these two possibilities from their own findings. Their family investigations suggest that an out-of-phase centromere separation may result in aneuploidy of the offspring even if it occurs in mosaic form in a part of the cells. At the same time, detailed investigation and anthropometric measurements of the parents of 28 children with multiple malformation syndromes revealed characteristic signs in at least one of the parents in 8 families. Among other factors also parental mosaicism should be taken into account, which should be considered in genetic counseling. PMID- 2204863 TI - [Ultrasonic diagnosis and treatment of a rare form of isolated gallbladder injury]. AB - A rare form of traumatic cholecystitis revealing a suffusion in the wall of the gallbladder with stones is reviewed by the authors. An isolated occurrence as such injuries is extremely rare. The possibilities and accuracy of preoperative ultrasonic diagnosis are discussed in diseases of the gallbladder. Similar reports in the literature of last ten years have not been found, therefore aim of the present report is to call attention to the disease which if left without treatment can be fatal. According to the authors an operative treatment is of vital importance in such cases. PMID- 2204864 TI - [Lajos Markusovszky, educator, physician, organizer, member of the Hungarian Academy of Sciences]. PMID- 2204865 TI - [Pathophysiological relations and clinical significance of serine protease inhibitors (serpins)]. AB - Serine proteases, like all other proteases, are biologically active substances. Their effects are inhibited by serine proteases inhibitors. The disturbance of balance between protease and antiprotease leads to several diseases and to their progression. The authors give an overview on some important data on serpins (biochemical parameters, structural composition), and on the clinical considerations of some diseases that are arisen from the changes in inhibitor levels. The paper includes some own examinations, too. Finally the possibilities of prevention and therapy are discussed. PMID- 2204866 TI - [Ultrasonic examination of the penis]. AB - Authors describe their experiences with penile ultrasonography. US was very useful in diagnostics of urethral strictures, urethral stones, Peyronie's plaques and for control of corpora cavernosa during papaverine induced erection. Application of ultrasonography for such purposes is very rare as yet, and the international literature referring to this is not very numerous either. According to authors' knowledge, this is the first paper in Hungarian dealing with this topic. PMID- 2204867 TI - [The Szontagh IUD and cervix carcinoma (results of a 10-year follow up study)]. AB - Based on a ten-year follow-up of 8334 Szontagh IUD (a non-medicated, Hungarian made device) cases, the author evaluates the connection between the IUD and the cervical cancer. At the end of the tenth year, the number of those at risk is 1159, and the cumulative woman-month of use is 397 817. During the observation period, 35 devices were removed for suspect colposcopic and/or cytologic findings. Using life table rates the author analyses the occurrence of the invasive and the in situ carcinoma, the dysplasia and those cases where the histopathology performed after the IUD removal resulted in "negative" finding. The 35 removals represent a 5.2 net cumulative termination rate at the end of the 120th month (calculated for 1000 women). The same figure for the 2 in situ and the 3 invasive carcinoma is 0.3 and 0.4, respectively. Evaluating the gross specific (annual) rates, it is stated that there is not any correlation between the duration of the IUD use and the occurrence of cervical malignancy; consequently, the intrauterine contraceptive device does not cause carcinoma. These rates were compared to the overall country figures, and the IUD users showed lower frequency. Of course, it does not mean that the device gives protection against malignancy, but it proves that the regular follow-up helps to discover the suspect cases in time. PMID- 2204868 TI - [In the footsteps of Markusovszky: the future of Orvosi Hetilap]. PMID- 2204869 TI - [The life span of Hungarian and foreign physicians in the light of obituaries published in medical journals]. PMID- 2204870 TI - [The postresuscitation changes in the permeability of the hemato-encephalic barrier and their possible pathogenetic significance]. AB - Experiments were conducted on rats with temporary (10-min) clamping of the thoracic vascular bundle and subsequent resuscitation to study the permeability of the blood-brain barrier (BBB) to plasma albumins and globulins and to blood plasma immunoglobulins in different stages of the postresuscitation period. Mild increase of BBB permeability was detected 3 minutes after the beginning of recirculation. Permeability increased markedly in 24 hours and continued growing by the 72nd hour. At a 1-3-hour interval in recirculation the BBB was closed. The obtained results disclose the mechanisms of the development of autoimmune cerebral disorders in an organism that experienced cardiac arrest and resuscitation. PMID- 2204871 TI - [The pathophysiological problems of emotional memory]. PMID- 2204872 TI - [The centenary of the Department of Pathological Physiology of the Tomsk Medical Institute]. PMID- 2204873 TI - [Clinico-allergic indicators in children with Yersinia infection]. PMID- 2204874 TI - [Increased sensitivity to Candida in patients with bronchial asthma]. AB - As many as 86 children aged 3 to 14 years with bronchial asthma were examined using mycological, immunological and allergological methods including the prick test, basophil degranulation test (direct Shelley's test) and leukocyte migration inhibition test with Candida antigen. As far as the patients living in the vicinity of a microbiological factory are concerned, hypersensitivity to Candida was detected in 83.3% of cases, primarily that of the delayed type (37%). In children with verified candidiasis, hypersensitivity to Candida fungi was also detectable in 83.3% of cases, but in the majority of patients (47%), it was of the immediate type. In the control group, allergic candidiasis was diagnosed in 20% of cases. Clinically, bronchial asthma associated with allergic candidiasis was characterized by refractory, lingering obstructive bronchitis amenable to antimycotic drugs. PMID- 2204875 TI - Oculomotor activity and the alpha rhythm. AB - From the beginning of clinical use of the EEG until now a close connection with oculomotor activity was assumed and empirically proven. After giving a sketch of the historical development, the issue is extended to the question of a connection between task-related alpha asymmetries and oculomotor activity. In doing so, the concepts of attention and cognition/emotion have to be dealt with. Referring to Kinsbourne, a conceptual framework is outlined which allows a mediation of the different methodical perspectives and thereby the formulation of testable hypotheses. PMID- 2204876 TI - Sex preferences of mentally retarded children depicted in the human figure drawn first. AB - This study was designed to investigate the effect of sex, age (5 to 18 yr), and IQ (20 to 78) of subjects on sex of human figures drawn first by 146 mentally retarded children. The results showed that the percentages of self-sex figures drawn first by mentally retarded boys and girls are statistically significantly lower than those for boys and girls of normal ability and that neither severity of retardation nor age is significant in determining the frequencies with which a self-sex figure is drawn first by mentally retarded boys and girls. It was suggested that minimal intelligence is required to learn the sex-identification and to identify with one's own sex. PMID- 2204877 TI - Phantom representations of congenitally absent limbs. AB - It has been widely claimed that phantom limbs are not experienced by children born without the part or who have it amputated in early childhood. This review looks at some reported cases of such phantoms, as well as a lesser known account that shows that phantoms of aplasics can be vivid and dexterous. Reasons for the infrequency of such reports are examined, and some implications for understanding the development of the body schema are proposed. PMID- 2204878 TI - Contributions to the history of psychology: LXVII. Henricus (Hans) Kuypers F.R.S. 1925-1989. AB - Hans Kuypers, who died in September 1989, was one of the founding fathers of neuroscience. Kuypers studied medicine in Leiden, The Netherlands and trained as a neuroanatomist with Nauta. His early work at Maryland and at Cleveland led to a wealth of new discoveries about descending motor pathways. Subsequently at Rotterdam, where he was foundation professor, and at Cambridge, England he searched for new brain probes, including retrograde fluorescent tracers and viruses for labelling chains of interconnected neurons. He saw the need to relate new neuroanatomical findings to brain function: in particular, how the brain steers hand and arm movements. He will be greatly missed by a long and distinguished list of collaborators on every continent. PMID- 2204879 TI - Sport expertise: the cognitive advantage. AB - The purpose of this article is to illustrate the significance of the cognitive system in sport expertise. Consideration of visual-perceptual abilities, along with cognitive factors and their relationship with sport expertise, suggest that level of sport performance can be reliably differentiated on several cognitive dimensions. Information is given concerning the cognitive requirements of sports skills. It is argued that although visual-perceptual abilities are inherent in all levels of sport performance, cognitive factors are essential for sport expertise. PMID- 2204880 TI - [Dentin adhesives]. AB - Chemical adhesion of resin based restorative materials to dentin using adhesives presents a complex problem due to the different nature of polymeric materials and tooth substance. It is indicated that the problems arise mainly from properties of the filling material, eg polymerization shrinkage. Glass ionomer cements exhibit excellent clinical retention in spite of the low bonding forces found in laboratory tests. PMID- 2204881 TI - Moments in nursing history. 1893. Of exclusion and divided houses. PMID- 2204882 TI - A lost art? PMID- 2204883 TI - Erythropoietin and blood donation. PMID- 2204884 TI - Oncology Nursing Forum and Index Medicus: together at last! PMID- 2204885 TI - Nursing research priorities related to HIV/AIDS. AB - To determine the nursing research priorities related to HIV/AIDS, a two-round Delphi technique survey was conducted. Registered nurses in clinical, administrative, academic, and research nursing positions identified a total of 208 topics. The highest-ranked items were patient-centered and lower-ranked items were provider-centered. Subjects in clinical practice identified the nutritional aspects of AIDS care and hospice care as being of higher priority than did subjects in administrative, academic, and research positions. Complementary therapies and healthcare providers' fears were ranked as higher priorities by the administrative, academic, and research nurses than by the clinical practice subjects. PMID- 2204886 TI - Patterns of nausea and vomiting in children: nursing assessment and intervention. AB - Although aggressive treatments for childhood cancer have resulted in an increased cure rate, increased incidence of treatment-related side effects also has occurred. Nausea and vomiting are two common side effects of cancer treatment in children. This clinical review discusses nursing issues related to the treatment of nausea and vomiting in children. Focus is placed on assessment, incidence and etiology of nausea and vomiting, patterns of nausea and vomiting, developmental influences on nursing intervention, innovative nursing strategies, behavioral interventions, specific antiemetic therapy, and home care. A need for further study of nausea and vomiting associated with childhood cancer treatment is identified. PMID- 2204887 TI - Resources in cancer pain management. PMID- 2204889 TI - An update in pediatric oncology. AB - Although childhood malignancies are rare, they represent the most common cause of death from disease in children less than 15 years old. Fortunately, the outlook for children with cancer has been improving steadily as newer methods of diagnosis, staging, and treatment are developed. PMID- 2204888 TI - Tips for success. PMID- 2204890 TI - [Prostaglandins and plasma renin activity during pregnancy and the puerperium in patients with hypertension]. PMID- 2204891 TI - [Motives and intentions of jubilee celebrations on the occasion of the 200th anniversary of medical education in Warsaw]. PMID- 2204892 TI - [Significance of stereoisomer drugs in therapy]. PMID- 2204893 TI - [50-year evolution of medical reflection in Poland]. PMID- 2204895 TI - Vitamin B12 deficiency. Important new concepts in recognition. AB - Vitamin B12 deficiency develops over a slowly progressive continuum. Early manifestations may be generalized weakness or fatigue, indigestion, diarrhea, or depression. Pernicious anemia is considered the classic cause, but others include malabsorption because of achlorhydria or other gastric dysfunction, fish tapeworm infection, and strict vegetarianism. Iron deficiency often coexists. Because presentation is often atypical, vitamin B12 deficiency is a diagnostic consideration whenever neuropsychiatric signs or symptoms are unexplained. PMID- 2204894 TI - Three blistering diseases. Why proper management is critical. AB - Dermatitis herpetiformis, pemphigus vulgaris, and bullous pemphigoid are uncommon, but not rare, blistering diseases. Accurate diagnosis is essential so that prognosis can be estimated and proper treatment begun. The systemic drugs used in treatment can cause major complications, and careful monitoring is vital. Management is best achieved with a team approach consisting of a primary care physician and a dermatologist. PMID- 2204896 TI - How to identify and manage brain hemorrhage. AB - With the aid of computed tomography, physicians are able to differentiate parenchymal brain hemorrhage from ischemic stroke. The most common sites of hypertensive hemorrhage are the putamen and thalamus. Lobar hemorrhages are not usually due to hypertension. Therapy for parenchymal brain hemorrhage is based on knowledge of the hemorrhage's natural history. Medical treatment is directed toward reducing blood pressure and intracranial pressure. A number of general factors must be considered before undertaking surgery, because indications are usually undefined. PMID- 2204897 TI - Very-low-calorie diets. Safe treatment for moderate and morbid obesity. AB - Very-low-calorie diets are a tedious but effective treatment for moderate and morbid obesity. An exercise program, nutrition counseling, and behavior modification are essential elements in the total program. Careful supervision by a knowledgeable physician and commitment by both the patient and the physician are essential. Although some side effects are inevitable with drastic weight reduction, current formulas are safer than those used in the past. PMID- 2204898 TI - Healthcare crisis. As I see it. What would you do to close the checkbook on runaway healthcare costs? PMID- 2204899 TI - Allergic bronchopulmonary aspergillosis. An increasingly common disorder among asthmatic patients. AB - Allergic bronchopulmonary aspergillosis (ABPA), an immunologic disorder, is characterized by bronchial colonization with Aspergillus species, resulting in chronic antigenic stimulation. Hallmarks of the disorder are asthma, cutaneous and serologic evidence of hypersensitivity to Aspergillus organisms, and fleeting pulmonary infiltrates. Diagnosis requires a high index of suspicion. Early diagnosis, aggressive therapy, and serial monitoring of serum IgE levels usually prevent progression of ABPA to bronchiectasis, pulmonary fibrosis, respiratory failure, and death. PMID- 2204900 TI - Cervical spondylotic myelopathy. A diagnostic challenge in aging patients. AB - Cervical spondylotic myelopathy remains a diagnostic and therapeutic challenge to physicians in a number of specialties. The diagnostic evaluation consists of a comprehensive neurologic and orthopedic examination supplemented by appropriate neurophysiologic and neuroradiologic studies. Currently, magnetic resonance imaging and myelography with computed tomography are the imaging methods of choice. Conservative therapy helps one half of patients with cervical spondylotic myelopathy, and surgery may benefit up to three quarters. Although this condition is entirely benign pathologically, its clinical manifestations appear malicious and deleterious. As new diagnostic and therapeutic techniques are refined, management of the disease should become even more successful. PMID- 2204901 TI - Throat culture or rapid strep test? AB - Clearly, rapid tests for streptococci identification are here to stay, and development of the technology is likely to continue. The most rational use of these tests is to identify streptococcal pharyngitis when patients have severe symptoms or when special situations warrant early detection. Throat culture alone is sufficient for most other patients, and all negative rapid tests should be confirmed by throat culture. Specific antistreptococcal therapy should be initiated if either the rapid test or culture is positive. If the physician decides on the basis of clinical criteria to treat pharyngitis with an antibiotic that covers group A beta-hemolytic streptococci, a rapid test is not necessary. If confirmation of the infection is warranted in these cases, throat culture alone should suffice. No rapid strep test kit clearly outperforms others. With any test, good results depend on the quality of the specimen. PMID- 2204903 TI - Microhematuria. Picking the fewest tests to make an accurate diagnosis. AB - Microhematuria is discovered fairly often and is bewildering to patients who are unaware that they have a urologic disease. Although it may indicate a life threatening process, in some instances, a thorough workup may be more dangerous to the patient than the disorder itself. Frequently, the cause of microhematuria does not require treatment. Dr Bartlow offers clues to pinpoint the anatomic site of bleeding so that treatable problems can be identified with the lowest cost and risk. PMID- 2204902 TI - Oral contraceptives and cardiovascular risk. Taking a safe course of action. AB - Although a prospective, longitudinal study on the long-term cardiovascular effects of oral contraceptives has yet to be performed, available data are useful in determining a safe course of action while physicians await definitive answers. Exogenous sex steroids produce important effects on lipid metabolism. Early intervention against cholesterol is important in reducing cardiovascular risk. Current users of high-dose formulations, particularly older women who smoke, are at greatest risk for cardiovascular complications, especially myocardial infarction. Low-dose oral contraceptives have more modest effects on lipid metabolism, but important differences in the potency of progestins remain. Fortunately, recent studies among users of lower-dose oral contraceptive formulations fail to show an increase in cardiovascular morbidity and mortality. Nonetheless, prudent physicians will avoid oral contraceptives that may adversely affect lipoprotein metabolism, such as those containing progestins with high androgenic and antiestrogenic potency. PMID- 2204904 TI - Bladder cancer. What's new in diagnosis and treatment? AB - Advances in diagnosis and treatment have improved survival rates, bladder preservation, and quality of life in patients with bladder cancer. Flow cytometry and flexible endoscopy have enhanced early diagnosis, and intravesical use of BCG vaccine has decreased the rate of recurrence and progression of superficial bladder cancer. Systemic chemotherapy is effective in patients with invasive and metastatic bladder cancer. Although these advances are encouraging, continued investigation is required to further improve bladder preservation and survival rates, and clinical application of laser therapy and phototherapy needs to be fully developed. PMID- 2204905 TI - Pulmonary embolism. How to 'nail down' the diagnosis. AB - Pulmonary embolism is a common problem in hospitalized patients. Because its initial symptoms may be nonspecific, pulmonary embolism may be difficult to diagnose. A high index of suspicion, together with careful selection of diagnostic tests, is essential. An algorithm for clinical assessment of suspected pulmonary embolism is presented here. PMID- 2204906 TI - Clinical management of short-bowel syndrome. Enhancing the patient's quality of life. AB - Management of patients following extensive small-bowel resection is complex. Parenteral nutrition is necessary initially because of a greatly reduced absorptive capacity. Intestinal adaptation occurs gradually and is stimulated by enteral feeding. Evaluation of specific nutrient status is essential, and supplementation may be required. The degree and consequences of malabsorption are more dependent on the anatomic location of resection than on the extent, but the outcome and eventual capacity for absorption in any given patient cannot be absolutely predicted. Even patients who do not achieve independence from parenteral nutrition receive many psychological and physiologic advantages by attaining the ability to consume some foods. Certain patients may subsist well on parenteral nutrition every other day without intravenous lipid. Such a regimen considerably reduces expense and simplifies clinical management, improving the quality of life. PMID- 2204907 TI - [Identity from the systems theory viewpoint]. AB - During the last two decades systems theory has changed. The theory of autopoietic (selfreferential) systems was introduced by Maturana and Varela and modified by Luhmann. The concept of identity is discussed in the light of the new theories. PMID- 2204908 TI - [Autopsy findings and pathologic-anatomic epicrisis]. PMID- 2204909 TI - [Immunohistochemical studies of the differential diagnosis of papillary tumors of the breast]. PMID- 2204910 TI - [Histogenesis of cardiac myxoma based on a myxoma with glandular structures]. PMID- 2204911 TI - [Primary osteosarcoma of the kidney. Case report and review of the literature]. PMID- 2204913 TI - [Small cell carcinoma with sarcomatous stroma. Immunohistochemical study of an unusual carcinosarcoma of the bladder]. PMID- 2204912 TI - [Immunohistochemical detection of estrogen and progesterone receptors in paraffin sections]. PMID- 2204914 TI - Failure of family history to predict high blood cholesterol among hispanic preschool children. AB - Recommendations for screening children for high blood cholesterol remain controversial. The American Academy of Pediatrics, the American Heart Association, and the National Institutes of Health (NIH) Consensus Conference have recommended targeted screening of children with positive family history. We examined data from a sample of 108 Hispanic preschool children and their families to test targeted screening strategies. Thirty-seven children (34.3%) had total cholesterol levels of greater than or equal to 4.40 mmole/liter (170 mg/dl). Using the American Academy of Pediatrics definition of family history, sensitivity (proportion of those with high blood cholesterol with positive family history) was 0.57 (95% confidence interval, 0.40 to 0.73) and accuracy (overall proportion correctly classified) was 0.58 (0.48 to 0.68). Using the American Heart Association and NIH Consensus Conference definition of family history, sensitivity was 0.46 (0.30 to 0.63) and accuracy was 0.62 (0.52 to 0.71). Classification of children based on the mother's total cholesterol level of greater than or equal to 5.17 mmole/liter (200 mg/dl), the mother's low-density lipoprotein cholesterol level of greater than or equal to 4.14 mmole/liter (160 mg/dl), the mother's low-density lipoprotein cholesterol level of greater than or equal to 3.36 mmole/liter (130 mg/dl), or the child's own body mass index greater than or equal to 75th percentile was less sensitive and no more accurate. These findings indicate that current recommendations as well as other potential strategies for targeted cholesterol screening in young children have serious shortcomings and lend support to universal cholesterol screening in childhood. PMID- 2204915 TI - Obesity and overweight in young adults: the CARDIA study. AB - The associations of body size with age, race, sex, and education in young adults were examined in 5,115 black and white, men and women ages 18-30 years. Black women were more obese than white women with greater mean levels of body mass index (25.8 vs 23.1 kg/m2), subscapular skinfold thickness (19.9 vs 15.2 mm), and waist girth (76.7 vs 72.0 cm), all P less than 0.0001. Black women were more likely to exceed 20% of ideal body weights (black women 23.7%, white women 9.1%, P less than 0.0001). No similar differences were found in men. Associations of measures of body size with age and education differed among race/sex groups. Body mass index and skinfolds increased with age among white and black men and black women, but not among white women. The association of education with obesity was negative among white women and positive among black men with no significant association noted among white men and black women. These data show a complex relationship between age, sex, race, education, and obesity in young adulthood. PMID- 2204916 TI - [Molybdenum as an air pollutant]. AB - Investigations into the reasons for the retarded growth and discolouration of a small area of a field of rape situated on the outskirts of Vienna revealed higher than normal levels of molybdenum in the soil (up to 430 micrograms/l) and in the water (up to 9.7 mg/l). The source of the pollution was traced to a neighbouring industrial plant that was emitting the metal via the chimney stack. A review of the literature on the toxic effects of molybdenum in general and as an air pollutant in particular is provided. This shows that, in contrast to animals, this effect is relatively small in humans and plants. Nevertheless, the occupation-related inhalation of the metal has been shown to be associated with pneumoconiosis and gout-like symptoms. PMID- 2204917 TI - [Alveolitis caused by furnishing a medical office]. AB - This article reports on the occurrence of an exogenous-allergic alveolitis that developed in a colleague who moved into new consulting rooms and an apartment. The diagnosis was established on the basis of typical X-ray picture, typical pulmonary function test findings, typical BAL and the histological findings established in transbronchial pulmonary biopsy material. The putative cause was moulds, the source of which could not be completely identified. In the history of an exogenous-allergic alveolitis, domestic allergens should be taken into account, even when such apparent sources of allergens as room humidifiers or pet birds are not present. PMID- 2204918 TI - Max Hamilton: a life devoted to psychiatric science. PMID- 2204919 TI - The impact of the Hamilton Rating Scale for Depression on the development of a center for clinical psychopharmacology research. PMID- 2204920 TI - French experiences with the Hamilton scales in comparison with other scales for depression and anxiety. PMID- 2204921 TI - Use of the Hamilton Depression Scale in general practice. PMID- 2204922 TI - The Hamilton Depression Scale and its alternatives: a comparison of their reliability and validity. PMID- 2204923 TI - Psychometric developments of the Hamilton scales: the spectrum of depression, dysthymia, and anxiety. PMID- 2204924 TI - Secretion and cell surface expression of IgG1 are impaired in human B lymphoblasts that lack HLA-A, -B, and -C antigens. PMID- 2204925 TI - Basolateral amino acid transport in the kidney. PMID- 2204926 TI - Nuclear transplantation as a method for cloning embryos. PMID- 2204927 TI - Regulation and role of phospholipases in host-bacteria interaction. AB - Deacylating phospholipases play essential roles in numerous biological events, requiring tight control of hydrolytic activity. Most cells, unless stimulated or perturbed, exhibit little phospholipid turnover. Activation of phospholipases A (PLA) is usually triggered by membrane perturbing conditions or agents. Some activators indiscriminately activate any PLA, others are highly specific. Our studies concern an activator that is a potent bactericidal protein with membrane perturbing properties, isolated from polymorphonuclear leukocytes (PMN), that is only cytotoxic for gram-negative bacteria and primarily responsible for the fate of several gram-negative bacterial species, ingested and killed by the PMN. It is this protein that activates the hydrolysis of the phospholipids of the killed bacteria (E. coli) by three PLA: 1) an E. coli PLA, the pldA gene product; 2) a PLA2 of PMN; 3) a soluble PLA2 in the extracellular fluid of an inflammatory exudate. However, this activator protein does not trigger the action of many other PLA2, all members of a highly conserved class of PLA. Our structural studies (including genetic engineering) of both responsive and non-responsive PLA2 have revealed that the amino acid composition and sequence of the NH2 terminal alpha-helix of the PLA2 molecule are major determinants of the ability of the PMN protein to activate a given PLA2. Our results provide another demonstration that these important enzymes have diverged during evolution to perform different biological functions. PMID- 2204929 TI - Differential expression of the human IL-1 alpha and beta genes. PMID- 2204928 TI - Dissociation of transcription from translation of human IL-1-beta: the induction of steady state mRNA by adherence or recombinant C5a in the absence of translation. PMID- 2204930 TI - The production of human interleukin-1 beta by blood monocytes. AB - Human peripheral blood monocytes can produce interleukin-1 (IL-1) beta following the addition of picogram amounts of bacterial lipopolysaccharides (LPS). The activation of IL-1 production by these cells can be mimicked by manipulation of specific biochemical pathways which appear to be independent of, and synergistic with, the pathways activated by LPS. Such pathways may be used by other physiological systems to modulate the production of IL-1. Both negative and positive modulation of IL-1 production can be described. Selected chemical antagonists of the arachidonic acid cascade have been shown to inhibit IL-1 production. The activity of such compounds does not appear to be related to their activity as inhibitors of cyclooxygenase or lipooxygenase enzymes or to activity as antioxidants. The intracellular form of IL-1 beta is limited to the precursor, which is found cytoplasmically. The release of IL-1 by activated cells appears to be regulated, in part, by the integrity of the microtubule system of the cells. PMID- 2204931 TI - Regulation of cachectin biosynthesis occurs at multiple levels. PMID- 2204932 TI - The three-dimensional structure of tumour necrosis factor. PMID- 2204933 TI - The role of cytokines as communication signals between leukocytes and endothelial cells. PMID- 2204934 TI - Pathophysiology of TNF/cachectin administered to nude mice. PMID- 2204935 TI - The complex effects of recombinant tumour necrosis factor-alpha (rhTNF-alpha) in human ovarian cancer xenograft models. PMID- 2204936 TI - Determination of the primary and secondary structure of NAP-1/IL-8 and a monocyte chemoattractant protein, MCP-1/MCAF. PMID- 2204937 TI - Proinflammatory cytokines interleukin 1 and tumor necrosis factor induce cytokines that are chemotactic for neutrophils, T cells and monocytes. PMID- 2204938 TI - Tumor necrosis factor-alpha, interleukin-8 and chemotactic cytokines. AB - There is little doubt that the high degree of communication observed during an immune response occurs via sophisticated cell-to-cell mediator circuits. The coordinate expression of specific signals are needed to orchestrate inflammation as the lesion is initiated, maintained, and finally resolved. Each of these phases can be viewed as a unique window of inflammation that is driven by a specific set of mediators. In this manuscript, we have developed the concept that cytokine-cytokine interactions play a prominent role in the elicitation of inflammatory cells. Our data demonstrate that the expression of chemotactic cytokines are both cell and stimulus specific. Interleukin-8, neutrophil chemotactic factor, can be synthesized by a variety of immune and non-immune cells, but the production is dependent upon an appropriate challenge. The production of monocyte chemotactic factor is much more cell restricted and appears to be generated in abundance by only non-immune cells (fibroblasts, endothelial cells, and epithelial cells). These data suggest that the recruitment of cells to a site of inflammation is dependent upon the expression of specific cytokines for both the induction and maintenance of the lesion. PMID- 2204939 TI - Anti-inflammatory peptides inhibit synthesis of platelet-activating factor. PMID- 2204940 TI - Prostaglandins and extracorporeal circulation. PMID- 2204941 TI - The Association of American Physicians: the Philadelphia connection. PMID- 2204942 TI - Early Greek theories of cognition: Homer to Hippocrates. PMID- 2204943 TI - Patenting medical inventions. PMID- 2204944 TI - Phytochrome and protein phosphorylation. AB - The molecular mode of signal transduction triggered by phytochrome is unknown. One characteristic structural/topographic feature of the physiologically active form (Pfr) of phytochrome is that its tetrapyrrole chromophore becomes preferentially exposed in the Pfr form (compared to the Pr form). Phytochrome in its Pfr form appears to affect phosphorylation of cellular proteins. The literature on the phytochrome-mediated protein phosphorylation has been reviewed in an attempt to search for the role of the chromophore topography of phytochrome in the signal transduction process. In order to initiate a dephosphorylation phosphorylation cascade as a possible step for the signal transduction, it may interact with a cellular protein kinase to inhibit its activity. This hypothesis has been reviewed with results from phosphorylation inhibition assays by the Pfr form of phytochrome and in light of the inhibition of protein kinase activity by tetrapyrroles in general. PMID- 2204945 TI - Phytochrome genes: studies using the tools of molecular biology and photomorphogenetic mutants. PMID- 2204946 TI - Rhythmic regulation of the light-harvesting chlorophyll a/b protein and the small subunit of ribulose-1,5-bisphosphate carboxylase mRNA in rye seedlings. AB - In etiolated rye seedlings transferred to light the expression of chlorophyll a/b binding protein mRNA varies when the seedlings are grown in a day/night cycle. The fluctuation pattern follows a circadian rhythm. Exposure of 4-day old etiolated seedlings to continuous white light revealed two maxima within the first 24 h before the 24 h cycle period appeared. These first two maxima are also observable after a pulse of white light or after a pulse of red light. These results indicate a possible involvement of phytochrome in the endogenous regulation of the rhythm. PMID- 2204947 TI - Analysis of the diurnal expression patterns of the tomato chlorophyll a/b binding protein genes. Influence of light and characterization of the gene family. AB - Steady-state mRNA levels of the chlorophyll a/b binding (cab) proteins oscillate substantially during a diurnal cycle in tomato leaves. This accumulation pattern is also observed in complete darkness, supporting the hypothesis that the expression of cab genes is at least partially regulated by an endogenous rhythm ("biological clock"). The amplitude of the cab mRNA accumulation is dependent on the duration of illumination and the circadian phase in which light was applied to the tomato plants. These results at the molecular level correlate well with the photoperiodic phenomenon. The characterization of the expression pattern of individual members of the cab gene family was attempted. Distinct primer extension products were detected using specific oligonucleotides homologous to the cab 1, cab 4, cab 5 and cab 8 genes. Based on this analysis the transcription start sites of these genes were determined to be between position -70 and -9 upstream of the ATG codon. During the diurnal cycle the cab 1 and cab 4 genes exhibit the same expression pattern; no transcripts detected at 3 and 6 a.m., maximum mRNA levels were measured at noon and decreasing levels in the afternoon. PMID- 2204949 TI - Plastic and Reconstructive Surgery. Cumulative index, 1984 through 1988. PMID- 2204950 TI - Richard F. Sterba 1898-1989. PMID- 2204948 TI - Phytochrome-regulated expression of genes encoding light-harvesting chlorophyll a/b-protein in two long hypocotyl mutants and wild type plants of Arabidopsis thaliana. AB - The cab genes which encode the light-harvesting chlorophyll a/b-protein (LHCP) are expressed normally with respect to phytochrome regulation in the hy-3 and hy 5 long hypocotyl mutants of Arabidopsis thaliana. In etiolated seedlings of these mutants as well as of the wild type, 1 min of red light elevates cab mRNA levels substantially within 2 h; this increase is reversed if far-red light is given immediately after the red light treatment. We conclude that the genetic defects in these mutants do not affect steps in the signal transduction pathway leading to the regulated expression of cab genes. Additionally, the mRNA from one of the three known A. thaliana cab genes, AB140, is similar in quantity to the mRNAs from the other two, AB165 and AB180, in dark-grown seedlings of hy-3 and hy-5 as well as the parent A. thaliana (Landsberg) after a brief red light treatment. This aspect of cab gene expression differs from the strain Columbia of A. thaliana in which AB140 mRNA is the predominant message. In mature white light grown plants of the strain Columbia, AB140 as well as a combination of AB165 and AB180 mRNAs are expressed at high levels, suggesting that AB165 and/or AB180 may be developmentally regulated. PMID- 2204951 TI - Life change, stress responsivity, and captivity research. AB - One purpose of a presidential address is to allow the speaker to identify seminal studies in their area of research which are generally unknown and likely were published before the advent of computerized searches of the scientific literature. Particularly in life change research, many important papers are obscurely placed and because of their early dates of origin are out of the computer's reach. Therefore, for this talk I will present some of this formative, but cloistered, material. Similarly, selected findings from early studies of biochemical correlates of life change stress could also bear repetition. For example, previously documented large variability in the serum concentration of these metabolites across varying life situations frequently goes unheeded, perhaps even unrecognized, by today's investigators. Finally, I wish to re acquaint many of you with the utility and clinical appeal of the life chart. From Meyer, Hinkle, Holmes, Rahe, and Theorell, illustrations of the origin, development, and current status of this approach to understanding the timing of illness onset will be presented. PMID- 2204952 TI - The role of anxiety in the development of anticipatory nausea in cancer chemotherapy: a review and synthesis. AB - The role of state anxiety in the development of anticipatory nausea and vomiting (ANV) in cancer chemotherapy has been the focus of considerable empirical investigation and theoretical speculation. However, while some relationship between state anxiety and ANV is presumed to exist, determination of its precise nature has proven elusive. Specific hypotheses linking state anxiety to ANV are described and evaluated in light of the empirical evidence. These hypotheses include (a) ANV is a symptomatic concomitant of state anxiety; (b) state anxiety directly facilitates the classical conditioning of ANV; (c) state anxiety exacerbates the magnitude of post-treatment nausea and vomiting experienced, thus increasing the risk of ANV; (d) ANV causes infusion-related state anxiety; and (e) the observed relationship between ANV and state anxiety is a result of methodological artifact. It is concluded that state anxiety can play a causal role in the development of ANV in some patients. In particular, the hypothesis that state anxiety exacerbates post-treatment nausea and vomiting and thus increases the risk for ANV appears best supported by the data. Finally, the clinical implications of the relationship between ANV and state anxiety for the treatment and prevention of ANV are discussed. PMID- 2204954 TI - Structural studies of protein-nucleic acid interaction: the sources of sequence specific binding. PMID- 2204953 TI - Tribute to Felix Deutsch. PMID- 2204956 TI - Color Doppler imaging: principles, limitations, and artifacts. PMID- 2204955 TI - Classification of macromolecular assemblies studied as 'single particles'. PMID- 2204957 TI - Teleradiology: an assessment. AB - A teleradiology system acquires radiographic images at one location and transmits them to one or more remote sites, where they are displayed and/or converted to hard copy. These systems often employ wide area networks. Their goal is to provide improved radiologic services at all sites on the network. Experience in the use of teleradiology systems has demonstrated the need for a laser film digitizer, an optical disk, and a high-quality display and/or laser film printer at each site. Single-site hardware purchase costs average $196,000, plus an additional 20% for yearly network services. Hardware purchased for a consultation or central referral facility approximates $344,000. PMID- 2204958 TI - Glucagon: common untoward reactions--review and recommendations. PMID- 2204959 TI - Intact stones or fragments? Potential pitfalls in the imaging of patients after biliary extracorporeal shock wave lithotripsy. AB - Ultrasound is used after extracorporeal shock wave lithotripsy of gallbladder stones to assess fragmentation. In many patients with apparently successful fragmentation, the posttreatment studies show an intraluminal, echogenic focus within the gallbladder, with posterior acoustic shadowing characteristic of an intact stone. Cholesterol gallstones were fragmented in vitro by means of lithotripsy, and the sonographic appearance of the fragmented stones was followed up over time to study factors that might affect the process. After lithotripsy, fragments settled and produced an echogenic focus with posterior shadowing indistinguishable from the appearance of an intact stone. These experimental observations led to the development of a clinical maneuver to overcome the diagnostic pitfalls posed by the reaggregation of stone fragments in situ. This rollover maneuver helps distinguish between intact stones and fragments, and prevents both diagnostic errors in follow-up and unnecessary retreatment. PMID- 2204961 TI - Cavitation effects during lithotripsy. Part I. Results of in vitro experiments. AB - Cavitation effects and microbubble formation are due to the rarefactive (negative pressure) component of shock waves. The in vitro application of shock waves generated by a commercial lithotriptor to an anthropomorphic phantom showed that stone fragmentation occurred more completely in fluid media that support cavitation than in a solid agar-graphite gel. Various fluids (saline, iodinated contrast material, bile) supported different degrees of cavitation. Bile exhibited cavitation at low energy and gave rise to intense microbubble formation at 19 kV. Cavitation increased dramatically with an increase in the rate of generation from 1.0 to 1.8 shock waves per second. The authors conclude that during biliary lithotripsy the environment of a stone will influence the extent of cavitation and fragmentation. PMID- 2204960 TI - Comet-tail artifact from cholesterol crystals: observations in the postlithotripsy gallbladder and an in vitro model. AB - The "comet tail" is a well-known ultrasound artifact that appears as a series of parallel bands radiating from a source. This artifact was observed in the gallbladder lumen in eight of 10 patients after extracorporeal shock wave lithotripsy of radiolucent calculi. To investigate the cause of the comet tail artifact, cholesterol crystals were studied in an in vitro model. The comet-tail appearance was reproduced in vitro and was found to be directly related to the interrogating frequency and the size of the crystal aggregates. The authors conclude that cholesterol crystals can serve as the source of the comet-tail artifact secondary to reverberation within the crystals. PMID- 2204962 TI - Cavitation effects during lithotripsy. Part II. Clinical observations. AB - Cavitation effects during biliary lithotripsy can produce sonographically visible microbubbles. The relationship between microbubble formation and clinical outcome of gallstone lithotripsy performed with a commercial lithotriptor was studied in 50 treatments in 29 patients. Microbubble formation in bile was a useful predictor of successful stone fragmentation in 31 of 34 treatments. Microbubble formation in the liver correlated with transient hepatocellular damage (as indicated by a twofold rise in serum transaminase levels) immediately after seven of 10 treatments. Advancing the focal volume of the lithotroptor deeper into the patient (placing the stone at the proximal point of the focal zone) may be a useful strategy for reducing hepatic cavitation effects, which appear to be responsible for temporary hepatocellular damage. PMID- 2204963 TI - Acute scrotal disorders: prospective comparison of color Doppler US and testicular scintigraphy. AB - Color Doppler ultrasonography (US) and testicular scintigraphy were used prospectively to evaluate 28 patients with acute scrotal pain. The results of these imaging studies were correlated with final diagnoses established by means of surgery or clinical follow-up. In all patients, testicular torsion was considered to be a possible diagnosis based on findings from the initial clinical evaluation. Findings from surgery confirmed testicular torsion in seven patients. All cases were correctly diagnosed with color Doppler US. Scintigraphy enabled correct diagnosis of six, but findings were false-negative in one patient with 180 degrees torsion. One patient had a surgically confirmed scrotal abscess that was correctly diagnosed with both color Doppler US and scintigraphy. Findings from clinical follow-up in the remaining 20 patients were consistent with epididymitis, orchitis, or torsion of an appendix testis. There were no false positive diagnoses of testicular torsion by means of either color Doppler US or scintigraphy in any of these 20 patients. Color Doppler US is at least as accurate as testicular scintigraphy and can function as an effective means of evaluating patients with suspected testicular torsion. PMID- 2204964 TI - Ovarian volumes measured by US: bigger than we think. AB - Authors have disputed the classic normal ovarian volume measurement of 6 cm3 without reference to a study with a large number of patients. To determine normal sonographic measurements, 762 consecutive female patients were examined. Satisfactory measurements of 1,157 ovaries in 725 of these patients were obtained. Average ovarian volumes of 9.8, 5.8, and 3.0 cm3 were obtained for the menstruating, postmenopausal, and premenarchal groups, respectively. These volumes were significantly different for these three menstrual groups (P less than .0001). Significant volume differences were noted when measurements were grouped by decade of life. Volumes peaked in the 3rd decade and declined over the subsequent four decade groups. A significant average volume difference was noted between pregnant (11.1 cm3) and non-pregnant (9.4 cm3) menstruating patients (P less than .0001). No significant differences in volume were noted between right and left ovaries or when the variables of weight, presence of a leiomyomatous uterus, or phase of the menstrual cycle were evaluated. PMID- 2204965 TI - Malacoplakia of the prostate sonographically mimicking carcinoma. AB - Malacoplakia is an uncommon granulomatous inflammatory disorder that usually affects the urinary bladder and only rarely affects the prostate. Prostatic malacoplakia was detected in five patients by means of transrectal sonography and confirmed by means of ultrasound-directed transrectal biopsy. Hypoechoic peripheral zone lesions, which are suggestive of carcinoma, were found in all five patients, including two with capsular irregularity and one with a lobular prostatic contour suggesting stage C disease. The results of this study suggest that, with the increased use of sonographically directed transrectal biopsy, prostatic malacoplakia may be found to be more common than previously suspected. PMID- 2204966 TI - Conjoined twins: prenatal diagnosis and assessment of associated malformations. AB - Prenatal diagnosis of conjoined twins is difficult and was rarely accomplished prior to the advent of sonography. Early prenatal diagnosis and assessment for shared vital organs are desirable for optimal obstetrical counseling and management. The authors retrospectively reviewed prenatal findings in 14 cases of conjoined twins. Thoracoomphalopagus was the most common type of conjoining, occurring in five cases (36%). Prenatal sonography showed shared hearts in nine (64%) cases, indicating severe conjoining and negligible chance for postnatal correction. Two sets of omphalopagus conjoined twins had separate hearts; however, severe congenital heart disease was present. Early prenatal diagnosis and assessment of the degree of conjoining provided couples with the option for pregnancy termination via vaginal delivery. In this series, nine patients elected pregnancy termination prior to 24 weeks and delivered vaginally. Transvaginal ultrasound significantly improved the delineation of conjunction in two patients, and computed tomography permitted the diagnosis to be confirmed in two patients. PMID- 2204967 TI - Assurance of consistent peak-velocity measurements with a variety of duplex Doppler instruments. AB - To assess the need for quality control when measuring peak velocities with Doppler ultrasonography, 17 duplex Doppler instruments from six manufacturers were compared by using a flow phantom that had been calibrated for peak velocities ranging from 23 to 75 cm/sec. Variations in peak-velocity measurements among machines averaged 23% when tested at the same flow rate with a Doppler flow phantom, indicating that scientific articles that document peak velocities for various disease processes should be accompanied by equipment calibration data. Doppler string and flow phantoms were compared, and each was found to have deficiencies. Techniques for quality assurance procedures for Doppler measurements are given that should achieve consistent peak-velocity measurements on serial scans of patients undergoing treatment for vascular conditions. PMID- 2204968 TI - Social relatedness and autism: current research, issues, directions. AB - Social relatedness has recently become a primary focus of investigators in the field of autism. This shift to regarding disturbances in social relatedness as one of the defining manifestations of the disorder marks the movement of research on autistic disorder back to its origins, when Kanner first noted the "social and affective" symptoms of autism as pathognomonic. Currently, social impairment in autism is viewed as more pervasively characteristic of the disorder than any other single symptom. Further, there has been a recent proliferation of research designed to document the nature of social deficit in autism, and whether it is primarily affective, communicative, or cognitive in nature, or involves some combination of these three variables. This review summarizes recent research focusing on social relatedness in autism and discusses the implications of these findings. PMID- 2204969 TI - [Respiratory function in cardiopulmonary transplantation]. AB - Today heart-lung transplantation (HLT) probably provides the best means of studying the role of pulmonary innervation in human respiratory physiology. Outside the periods of postoperative complications ventilatory function, blood gases and exercise tolerance of HLT recipients are compatible with a normal sedentary life. Control of breathing in the waking state at rest, and when asleep, in HLT subject is not different from that of the healthy subject, which suggests that the pulmonary afferents play a negligible role in the control of breathing of adult humans at rest. The results of the ventilatory response to carbon dioxide and to exercise in HLT subjects are contradictory and do not enable any conclusion about the role of pulmonary innervation in these types of integrated responses. On the other hand, the existence of bronchial hyperreactivity to cholinergic stimulation is well established, and is attributed to an upregulation of bronchial muscarinic receptors. An increase in the bronchial response to distilled water observed in some HLT subjects seems on the other and related to episodes of lung rejection. The reflex theory of cough is supported by studies of HLT subjects. Results of studies of the effect of a deep inspiration on bronchomotor tone are far from concordant. Other studies including a large number of subjects and looking at the presence or the absence of reinnervation after transplantation are perhaps two supplementary means to further investigate the respiratory function of HLT patients. Knowledge of the latter would equally enable a better understanding of control mechanisms of human respiratory physiology. PMID- 2204970 TI - [Chemotaxis and cellular migration in respiratory pathology]. AB - Numerous types of cells have a capacity for movement in physiological or pathological situations. For example, this is the case for inflammatory cells in the lung, during acute lobar pneumonia, sarcoidosis and idiopathic pulmonary fibrosis. Cellular migration is a general process which rests on the interaction between different chemotactic factors and specific receptors which are present on the target cells. On the other hand the addition of inhibitors can significantly decrease the cellular migration in the presence of chemotactic factors. In respiratory pathology, congenital chemotactic defects are exceptional (and the Chediak-Higashi syndrome and Job syndrome are examples). In contrast during the course of lung cancer, circulating monocytes often show a significant decrease in their chemotactic responsiveness. PMID- 2204971 TI - [Respiratory function abnormalities and pneumonia in HIV-positive patients. A prospective study of 112 patients]. AB - Pulmonary function studies are often limited to the alone measurement of transfer lung factor for CO (TLCO) in screening for pneumonia in patients with Human Immunodeficiency Virus (HIV) infection. We prospectively measured pulmonary function tests (PFT) in 112 HIV seropositive patients. The population consisted of two groups: on one hand, a group free of clinical and radiological abnormalities, on the other hand, one with respiratory symptoms and/or abnormal chest X-Ray, with or without overt pneumonitis. For this latter group, a fiberoptic bronchoscopy with bronchoalveolar lavage was routinely performed in addition to PFT. In case of pneumonitis, PFT showed a restrictive disease and a reduced TLCO. The specificity of this functional pattern was however weaker in the subgroup of drug abusers than in the non-drug addicts. This difference was above all linked to a low TLCO value in the subgroup of drug addicts without pulmonary complications. Multivariate statistical analysis, including discriminant analysis, maintained the same sensibility and improved specificity of PFT in diagnosis of pneumonia, especially if the analysis takes the existence of drug abuse into account. Moreover, initial PFT, performed before any lung disease, improved the sensibility of the screening. The results are discussed in relation to new tests proposed for the screening of pneumonitis in HIV positive patients. At the present time, PFT seems to be useful and enables one to understand natural functional evolution. PMID- 2204972 TI - Intraepithelial neoplasia of the lower genital tract. AB - The incidence of CIN, VIN, and VAIN has increased dramatically in recent years due to a true increase in disease incidence as well as improved screening methods. Associated high-risk factors in the development of intraepithelial neoplasia are known, and effective treatment modalities are available. With the use of diagnostic techniques, patient education, and selection and utilization of appropriate therapies, intraepithelial neoplasia of the lower genital tract remains a disease that should not affect long-term morbidity, social status, or mortality of female patients. PMID- 2204974 TI - Cancer of the vulva and vagina. AB - Vulvar and vaginal cancer are rare malignancies and require aggressive treatment for survival. The prospect for cure in early stage disease is excellent. The major treatment modalities for these diseases, surgery and radiation, will affect structural alteration of the genitalia, requiring physical and psychological rehabilitation over an extended period of time. Quality of life is an important focus in cancer nursing. Efforts to control symptoms or adverse effects and to enhance the psychological adjustment are important aspects of patient care. Vulvar and vaginal cancer leave obvious residual effects, and disfigurement and dysfunction will be a part of these women's lives. Husbands and partners are also affected, and adjustments of both the patient and her partner are expected to continue for years. An active position assumed by the nurse will aid the patients' adaptive responses to these devastating diseases. PMID- 2204973 TI - Cancer of the cervix. AB - Since the introduction of the Papanicolaou smear and colposcopy, cervical cancers can be diagnosed and treated easily in their preinvasive state. Although theoretically cancer of the cervix should be detected and treated before becoming invasive disease, there are still too many women who develop invasive cancer of the cervix and require radical surgery and/or radiation therapy. The management of patients with recurrent or advanced disease is difficult and challenging. PMID- 2204975 TI - Cancer of the endometrium. AB - Cancer of the endometrium is the most common and curable gynecologic malignancy. It has a most easily recognizable symptom in its usual presentation as postmenopausal bleeding. Treatment may vary considerably based on prognostic factors and may include surgery, radiotherapy, hormonal manipulation, or cytotoxic chemotherapy. Rehabilitation is the focus of nursing intervention and is initiated at the time of the cancer diagnosis. The continued effort by investigators to define intermediate and high-risk populations and, thus, appropriate adjuvant treatment will continue to reduce mortality from endometrial carcinoma. PMID- 2204976 TI - Psychosexual issues: the woman with gynecologic cancer. AB - Psychosexual concerns often confront women with a diagnosis of gynecologic cancer. These concerns can be physiologic or psychological in origin. Oncology nurses are in a key position to assess these potential or actual sexual problems. Interventions can be designed to prevent or minimize the adverse sexual sequelae often associated with this group of diseases. A strong knowledge base and comfort with the topic of sexuality are of utmost importance. PMID- 2204978 TI - [Physiopathology of non-insulin-dependent diabetes: current data and therapeutic consequences]. AB - Non insulin-dependent diabetes mellitus results from the combination in varying proportions of low plasma insulin levels (insulinopenia), peripheral resistance to insulin and increased hepatic glucose production. Abnormalities of insulin secretion can be demonstrated without and after stimulation. Insulin resistance mainly occurs in skeletal muscle and is primarily due to a "postreceptor" defect. A pancreatic peptide, amylin, may participate in insulin resistance. Hepatic glucose production correlates with high fasting plasma glucose concentrations. Whatever its initial mechanism, hyperglycaemia maintains low insulin secretion and insulin resistance by its toxicity. In the light of these data, the effects of weight loss in obese non insulin-dependent diabetics have become clearer. The action of biguanides on insulin sensitivity is confirmed. Sulphonylureas have a pancreatic and an extrapancreatic action. The normoglycaemia obtained by intermittent insulin therapy can break the vicious circle of glucose toxicity. The use of prolonged insulin therapy is discussed. Finally, new compounds with an original mode of action offer hopes for the future. PMID- 2204977 TI - [Current concept of pseudodementia]. AB - The concept of pseudodementia was coined in the late XIXth century to refer to a syndrome mimicking dementia, but without underlying neurological lesions. Depressive disorders represent the main etiological factor and may present under two different forms, either "depressive cognitive disorders", or the more severe feature of "Wernicke's pseudodementia". The main issue remains diagnosing pseudodementia form organic dementia, especially from cortical degenerations of the Alzheimer type. Thus, the recognition of this clinical syndrome represents an alternative to the diagnosis of dementia which may lead to earlier and more effective psychiatric treatment. Recently, diagnostic criteria have been proposed to facilitate this distinction. Such criteria include clinical history, neuropsychological features, biological findings (dexamethasone suppression test and plasma MHPG) and electroencephalographic sleep studies. Finally, from a theoretical point of neurological conception of depression as well as for current hypotheses on the relationship of this last one with dementia. PMID- 2204980 TI - Total androgen ablation in the treatment of metastatic prostatic cancer. The Canadian Anandron Study Group. PMID- 2204979 TI - [Treatment of prolactinoma]. AB - Prolactinomas rank first in frequency among hormone-secreting pituitary adenomas, but their management remains controversial. The authors present a review of the literature concerning the various therapeutic methods used and their results. As regards microadenomas, opinions are divided since the results obtained with bromocriptine and with selective adenomectomy are about the same. As regards macroadenomas, surgery exposes to more frequent complications and above all to recurrences. The majority of authors is in favour of bromocriptine first followed, if necessary, by surgical excision. Pregnancy may accelerate the development of prolactinomas. This risk is minimal with microadenomas and more real with macroadenomas, requiring more radical treatment before pregnancy and close monitoring. PMID- 2204981 TI - Neoadjuvant therapy of carcinoma of the bladder. PMID- 2204982 TI - Neoadjuvant chemotherapy in deeply invasive bladder cancer: the Italian experience. The Lombard Urologists. PMID- 2204983 TI - [Typhoid fever]. AB - The second part of this review accounts on a patient with classic symptoms of typhoid fever. The case history is commented in the light of todays knowledge. The case was taken from the clinical notes of Schonlein one of the most famous clinicians of the first part of the 19th century. It reveals the difficulties of the physician to cope with such a disease without our present diagnostic and therapeutic possibilities. It is surprising to realize that 150 years ago therapy of typhoid fever was not substantially different from that in use up to the recent introduction of specific antibacterial therapy. Since the typical course of typhoid fever is only rarely encountered nowadays the case seems suitable to recall this clinical picture to our generation of physicians. PMID- 2204984 TI - [Why does the dental prosthesis not stay in its place?]. PMID- 2204985 TI - [Loss of psychic self-activation]. AB - Loss of motivation is a well-known disorder in patients with frontal lesions or, as more recently described, with bipallidal lesions. Some of these patients also report a kind of fading of their mental life when they are without exogenous stimulation. Yet their performances return to normal (or almost normal) levels under the influence of a social stimulation. It is this dissociation which we propose to call "loss of psychic self-activation" (LPSA). Comparisons with disorders produced by similar lesions suggest that this is not an "all or none" phenomenon. The purpose of this paper is to discuss the originality, usefulness and validity of the loss of psychic self-activation concept and to evaluate its heuristic value, notably in its application to Janet's psychasthenia and to obsessional neurosis. An interpretation of this disorder based on the available anatomical data is also tentatively proposed. PMID- 2204986 TI - [Cortical pain. Clinical, electrophysiologic and topographic study of 12 cases]. AB - Vascular lesions of the cerebral cortex sparing the thalamus (MRI or CT with reconstructions) may be accompanied by burning or constrictive pain which suggests thalamic pain as it affects one half of the body and is associated with induced pain. Summation hyperpathia is rare; allodynia is more common and sometimes isolated (2 cases). Cortical pain may be paroxysmal, and in 3 of our patients it progressed like a jacksonian seizure. The territory of pain is also the site of global or spinothalamic hypoaesthesia (5 cases). Early SEPs are abolished or of low amplitude (8 cases). The lesion is located in area SI or extends to the thalamo-parietal radiations; in 11 out of 12 patients it was located in the minor hemisphere. Two physiopathological theories are discussed: hyperactivity of the intralaminar thalamus relieved from cortical inhibition, or denervation hyperactivity related to the cortical or subcortical lesion. PMID- 2204987 TI - [Oculopharyngeal muscular dystrophy. A census of French families and genealogic study]. AB - The first results of a collaborative study aimed at collecting all French families affected by oculopharyngeal muscular dystrophy (OPMD) and their genealogy are presented. The study was carried out in 28 families in whom the diagnosis of OPMD in the propositus was confirmed by the presence of typical intranuclear tubulo-filamentous inclusions in the muscle biopsy. Results suggest that the prevalence of OPMD in France is at least of 1/200,000. The disease has been observed in many countries but to our knowledge no epidemiological studies have been reported so far. However, it is known to be particularly frequent in the French-Canadian community living in Canada and USA. In the present study genealogical researches were carried out in 18 families. Three families were of Italian and two of Armenian origin. Amongst the 13 families of French ascent, 3 familial relationships were found: one from a couple married in 1783. In the other 10 French families, no interlineage was discovered in a genealogical enquiry pursued back to the 18th century. Further studies are needed to find out whether there was only one mutation responsible for all French cases or whether several mutations occurred in France, as suggested by the present study. It would be also interesting to ascertain whether there is a parental link between the French and the French-Canadian OPMD patients, the latter considered to be descendants of a couple who emigrated to Quebec in 1634. PMID- 2204988 TI - [Monomelic segmental amyotrophy: a Spanish case involving the leg]. AB - A 65-year old male presented with selective amyotrophy of the right lower limb which, after a progressive course of some months, had stabilized 12 years previously. Physical examination showed amyotrophy involving the gastrocnemius and the quadriceps extensor femoris without sensory impairment. EMG suggested motor neuron disease. This case meets Hirayama and Serratrice's criteria for benign chronic monomelic amyotrophy. We support the hypothesis of a casual vascular factor, as proposed by Hirayama. PMID- 2204989 TI - [Slowly progressive motor neuron disease associated with paralysis of the abductor muscles of the vocal cords]. AB - Some cases of slowly progressive motor neuron disease with bilateral paralysis of the vocal cord abductor muscles have recently been published. We report a case with a more than forty year's course occurring in a family in which one brother and probably 2 cousins died of motor neuron disease. PMID- 2204990 TI - [Recurrent herpetic encephalitis]. AB - A 64 year-old woman experienced, at 6 weeks' interval, two episodes of encephalitis with left hemiparesis, coma and signs of meningitis. Paraclinical examinations showed lymphocytic meningitis, right temporal hypodensity at CT and high titers for herpes simplex at blood serology. The spontaneous course was favourable with almost complete recovery. A third recurrence took place 2 months later with left hemiplegia, confusion and meningism. A tentative diagnosis of herpes simplex encephalitis was confirmed by major intrathecal synthesis of herpes virus specific antibodies and by highly suggestive MRI images. Treatment with acyclovir resulted in rapid regression of motor deficit and meningism, but neuropsychological disorders regressed more slowly with persistent visuo constructive and memory disorders. During a fourth and milder recurrence, a stereotactic temporal brain biopsy was performed, which showed lesions of encephalitis and elevated titers for HSV1 in the temporal fluid. Another course of acyclovir followed by vidarabine produced complete remission. The possibility of recurrent types of herpes simplex encephalitis is discussed. PMID- 2204991 TI - [Metastasis to the pituitary stalk in a case of breast cancer]. AB - A 64-year old woman with breast cancer developed diabetes insipidus. CT scan showed thickening and contrast enhancement of the pituitary stalk highly suggestive of metastasis. The patient was successfully treated with desmopressin followed by external radiation therapy. PMID- 2204992 TI - Intercellular communication in bronchial epithelial cells: review of evidence for a possible role in lung carcinogenesis. AB - A challenging aspect of lung carcinogenesis is the elucidation of the mechanisms which permit initiated bronchial epithelial cells to attain a growth advantage over normal bronchial epithelial cells, and subsequently evolve into a malignant phenotype. In this review, the effects of interactions between normal and transformed cells, and the potential role of representative extrinsic factors on cell-cell communication are discussed. Evidence is presented to show how cell injury and the effects of serum and calcium may affect morphology and communication, and tumor development. A large number of autocrine-paracrine factors (e.g., TGF beta, TGF alpha) are released by bronchial epithelial cells. These factors may inhibit or promote the proliferation of normal and transformed bronchial epithelial cells, respectively. The ability of certain injurious and tumor promoting agents (e.g., formaldehyde, TPA) to select for the transformed phenotype may involve selective cell injury, the induction of terminal differentiation and an inhibition of gap junction communication among normal BE cells. PMID- 2204993 TI - [Angiography and angiotherapy in diseases of the pelvic organs]. AB - The value of angiography is based on the fact that it enables the imaging of vascular processes (haemorrhage, aneurysm) and occasionally also the imaging of the vascular supply of tumors not related to any organ. Transarterial treatment procedures in the pelvic region, whether embolisation or intra-arterial chemoembolisation or intravasal radiotherapy, are on the whole rarely employed. They are important in palliative therapy of advanced and often inoperable neoplasms that cannot be treated otherwise. Transcatheter embolisation is an imhaemorrhages in the region of the a. iliaca int. or for arteriovenous malformations. PMID- 2204994 TI - Cholelithiasis in a 5-year-old girl--case report. AB - A case of cholelithiasis in a 5-year-old girl is presented in which the main symptom was recurrent pain of the upper abdomen. The diagnosis was made by ultrasound examination of the abdomen and confirmed at surgery. Possible etiological factors of gallstones in children are discussed and the role of abdominal ultrasound examination is emphasized. PMID- 2204995 TI - Influence of cisapride on food-stimulated gastro-oesophageal reflux: a radiological study. AB - The influence of Cisapride on food-stimulated gastro-oesophageal reflux mechanisms was studied in a double-blind cross-over investigation in 24 consecutive patients selected by endoscopy, 12 with microscopical evidence of gastro-oesophageal reflux and 12 with additional macroscopic oesophagitis. 63% had food-stimulated gastro-oesophageal reflux, and Cisapride significantly reduced the tendency to gastro-oesophageal reflux and mucosal contact time between gastric content and the oesophageal mucosa in 73% of these patients. It is concluded that Cisapride could be valuable in the treatment of gastro oesophageal reflux. PMID- 2204996 TI - [Salmonella osteomyelitis involving multiple bones in chronic myeloid leukemia]. AB - Salmonella osteomyelitis associated with sickle cell anemia has been reported in numerous cases and also in few cases of patients under immunosuppression or suffering from malignant disease. Involvement of multiple bones by an infection with salmonella typhimurium is rare. Intracortical fissures which are detectable on x-ray films after some weeks are looked upon as typical for a salmonella osteomyelitis. Bone scan, computed tomography or MR tomography are supplementary examinations in the diagnosis of salmonella osteomyelitis. PMID- 2204997 TI - [Cervical wedge-shaped lacunae and dentin hypersensitivity--a histological and SEM study]. AB - The purpose of this study was to establish a correlation between dentinal hypersensitivity and tissular modifications of the pulp-dentinal complex at the level of cervical abrasions. 65 freshly extracted human teeth (from patients aged 20 to 80 years) presenting cervical abrasions without carious lesions were prepared in order to be examined histologically (31 teeth) and by scanning electron microscopy (34 teeth). Open tubules were present on the abraded surfaces in 83.3% of the specimens with presence of cytoplasmic processes in 78.46% of the cases without any correlation with tooth age and depth of the abrasions. The sensitivity could be partially explained by the persistence of cervical dentinal permeability. This permeable dentin seems to be susceptible to mechanical, chemical and bacterial irritations, no matter how thick the reactional dentin is. In the absence of any reliable and biological product capable to seal efficiently the open tubules, only nonabrasive hygiene methods can preserve the integrity of cervical dental tissues. PMID- 2204999 TI - [The odontogenic keratocyst. Its epidemiology, clinical picture, differential diagnosis and therapy]. PMID- 2204998 TI - [The flexible gingival epithesis. The practical procedure, laboratory technics and clinical experience]. PMID- 2205000 TI - [The chicken egg as a supply of polyclonal antibodies]. AB - Polyclonal antibodies can be isolated not only from the blood of immunized mammals but also from the egg yolk of immunized chickens. The advantages of this alternative method are: 1) Birds produce antibodies against highly conserved mammalian proteins. 2) The quantity of antigen needed for an efficient immune response is very low (20-30 micrograms). 3) The use of complete Freund's adjuvant leads to long lasting titers of yolk antibodies yielding a total amount of 65 mg specific antibodies per month. 4) The purification of antibodies is simple, inexpensive and quick. Polyethylene glycol precipitation is sufficient to obtain a purity of more than 90%. 5) Chicken antibodies are acid- and heat-resistant and might therefore be orally applied to prevent or to cure infectious intestinal diseases of young animals or humans. 6) Immunization with complete Freund's adjuvant is well tolerated and produces no inflammatory reactions and 7) collecting eggs is, in contrast to bleeding animals, non-invasive. In this review we present both, the method how to produce and to isolate yolk antibodies as well as their possible application in science, diagnosis, prophylaxis and therapy. PMID- 2205001 TI - [Nocardia mastitis in cattle. 1. Clinical observations and diagnosis in 7 particular cases]. AB - Lately reports of nocardial mastitis have been increasing. Therefore the clinical aspects of 7 individual cases were investigated. Pathologic-anatomical changes of the udder were registered and bacteriological examination of tissue and milk probes were performed. All of the cows had a mastitis during previous lactation periods which had to be treated with antibiotics. The infected quarters recovered in no cases. Shortly after parturition 6 cows had a severe acute mastitis. The cows were treated intramammarily and parenterally with various antibiotics during several days. The infected quarter became indurated and strongly enlarged. These changes were not influenced by therapy, and the cows lost weight. 14 days after the outbreak of the illness, all 6 cows were culled. One cow had a chronic Nocardia mastitis with involution of the affected quarter. Though treated several times, this cow did not recover either. The histopathological examination of the affected quarters revealed an acute to chronic, necrotic to granulomatous mastitis. Nocardia asteroides was histologically and bacteriologically proven to be the causative agent. The reason for the frequent infections with Nocardia and the way of infection is not clear yet. Therapy with antibiotics brought no recovery in any cases. The infected cows should be removed from the herd or culled. PMID- 2205002 TI - Fragments of the HIV-1 Tat protein specifically bind TAR RNA. AB - Proteolytically produced carboxyl-terminal fragments of the human immunodeficiency virus type-1 (HIV-1) Tat protein that include a conserved region rich in arginine and lysine bind specifically to transactivation response RNA sequences (TAR). A chemically synthesized 14-residue peptide spanning the basic subdomain also recognizes TAR, identifying this subdomain as central for RNA interaction. TAR RNA forms a stable hairpin that includes a six-residue loop, a trinucleotide pyrimidine bulge, and extensive duplex structure. Competition and interference experiments show that the Tat-derived fragments bind to double stranded RNA and interact specifically at the pyrimidine bulge and adjacent duplex of TAR. PMID- 2205003 TI - Differentiation of mouse erythroleukemia cells enhanced by alternatively spliced c-myb mRNA. AB - C-myb, the normal cellular homolog of the retroviral transforming gene v-myb, encodes a nuclear, transcriptional regulatory protein (p75c-myb). C-myb is involved in regulating normal human hematopoiesis, and inhibits dimethyl sulfoxide-induced differentiation of Friend murine erythroleukemia (F-MEL) cells. An alternately spliced c-myb mRNA encodes a truncated version of p75c-myb (mbm2) that includes the DNA binding region and nuclear localization signal present in the c-myb protein, but does not contain the transcriptional regulatory regions. Constitutive expression of mbm2, in contrast to c-myb, here resulted in enhanced differentiation of F-MEL cells. These data suggest that the c-myb protooncogene encodes alternately spliced mRNA species with opposing effects on differentiation. PMID- 2205005 TI - Neurosurgical travel club. PMID- 2205004 TI - Dural carotid-cavernous sinus fistula and central retinal vein occlusion: a case report and a review of the literature. AB - A case of dural carotid-cavernous sinus fistula was complicated by hemorrhagic retinopathy due to central retinal vein occlusion. A 57-year-old woman with a dural carotid-cavernous sinus fistula was initially treated by transarterial particulate embolization. Her symptoms subsequently improved, but 4 months later she gradually developed decreased visual acuity due to central retinal vein occlusion. A review of the literature showed that central retinal vein occlusion may be more common than previously thought. Dural carotid-cavernous sinus fistulas should be treated and followed taking into account possible complication by central retinal vein occlusion. Early detection of central retinal vein occlusion by frequent ophthalmologic examinations may prevent deterioration of visual acuity. PMID- 2205006 TI - [Oral health in institutionalized elderly]. AB - In Denmark, approximately 7% (50,000) of the population above 65 years of age live in nursing homes (NH), where they stay for the rest of their lives, whereas elderly in hospital long-term care (LTC) are institutionalized only for a few months. Numerous studies report generally poor oral health among the institutionalized elderly, and the existing oral health care services are far from satisfactory. Attitudes towards the elderly, transportation problems, age, and dental status are among the variables that have been mentioned as possible determinants for utilization of dental services and for the standard of oral health among the residents. Utilization of health care services, including dental services, depends not only on the characteristics of the consumer, but also on the society and the provider. The planning of dental care for the institutionalized elderly requires information about the need for treatment, the existing possibilities for oral health care, and the institutional staff's attitude towards the elderly and dental care. It is also necessary to take into account the perceived need and the expressed demand for treatment as well as the mental and physical health of each individual in order to estimate what in the present study is defined as the realistic treatment need. PMID- 2205007 TI - Means and methods in oral hygiene instruction of adults. A review. PMID- 2205008 TI - [Influence of color combinations in determining color selection for dental restorations]. PMID- 2205009 TI - [Glass ionomers--coronal restorations. 1. Use of Cermets as restorative materials in endodontically treated teeth]. PMID- 2205010 TI - [Resin bonded metal-ceramic bridge]. PMID- 2205011 TI - [Rebonding of resin bonded bridge to a displaced abutment tooth, which has been moved into its original position by orthodontic treatment]. PMID- 2205012 TI - [Use of ear-muffs for noise reduction?]. PMID- 2205013 TI - [Clinical experience in the use of resin bonded veneers]. PMID- 2205015 TI - Two encounters with Medicare. PMID- 2205014 TI - [Glass ionomer as an alternative to amalgam]. PMID- 2205016 TI - Medicare and Texas medicine. 25 years of an uneasy alliance. PMID- 2205017 TI - The uneasy alliance between physicians and Medicare: what's TMA doing about it? PMID- 2205018 TI - More on selection for and against recombination. PMID- 2205020 TI - Use of biofeedback in the treatment of stroke patients. PMID- 2205019 TI - Thrombin-antithrombin III-complex & fibrin degradation products in plasma: surgery and postoperative deep venous thrombosis. AB - Thrombin-antithrombin-III complexes (TAT) & D-dimer in plasma, and fibrin(ogen) degradation products (FDP) in serum, were measured in 48 patients subjected to total hip arthroplasty. Blood samples were collected on days -1, 0, 1, 3, 7 and 10. Five patients developed postoperative deep vein thrombosis (DVT) diagnosed by venography. A characteristic pattern of TAT and D-dimer secondary to surgery was demonstrated. A poor correlation was found between ELISA- and latex-D-dimer concentrations after the operation. Patients with DVT had significantly higher TAT-levels preoperatively, and on day 0, 7 and 10. The concentration of FDP was significantly elevated in patients with DVT on day 7 and that of ELISA D-dimer on days 0 & 10. None of the assays are clinically valuable for purposes of postoperative screening for DVT. The preoperative plasma TAT concentration may represent a valuable predictive marker of postoperative DVT. PMID- 2205021 TI - Time intervals, survival, and destination. Three crucial variables in stroke outcome research. PMID- 2205022 TI - Classification of stroke for clinical trials. PMID- 2205023 TI - Measurement of stroke rehabilitation outcome in the 1980s. PMID- 2205024 TI - Family functioning assessment techniques in stroke. PMID- 2205025 TI - Dementia associated with stroke. PMID- 2205026 TI - Dietary habits in Spain: an approximation. AB - The dietary pattern of a population sample of males selected as a control group for a case-control study on bladder cancer carried out in four different regions of Spain is presented. Out of 807 population controls initially selected, 530 were interviewed, 465 males and 65 females. The method of selection of the study subjects and the diet assessment method are described. Our results confirm the Mediterranean pattern of the Spanish diet, with an important consumption of fresh fish, fruits and vegetables, and the use of vegetable oils, specially olive oil, for cooking and seasoning, accompanied with a high polyunsaturated/saturated ratio (0.7). The consumption of butter, cheese and other dairy products, on the other hand, is very low. Estimated total caloric intake is relatively low if compared with international figures, although questionnaire base assessment may seriously underestimate caloric intake, as it is the absolute amount of intake of lipids and carbohydrates. In relative terms, however, lipids provide the highest percentage of calories. PMID- 2205027 TI - Diet and epithelial cancer of the thyroid gland. AB - Enhanced secretion of thyroid stimulating hormone (TSH) has been linked with increased risk of thyroid carcinoma. Diet can increase TSH secretion in various ways: 1) low iodine intake, 2) high goitrogen intake, especially in subjects living in iodine-deficiency areas and 3) direct stimulation of anterior pituitary gland. Excessive iodine intake, however, has also been shown to increase risk of goitre and, perhaps, also thyroid carcinoma. Epidemiological evidence on the role of diet in the etiology of thyroid carcinoma is reviewed here. Ad hoc studies in affluent countries are few and often conflicting. A case-control study conducted in the North of Italy suggests that perhaps dietary aspects other than iodine or goitrogens (i.e. fresh fruit and vegetables and animal fat) may be involved. PMID- 2205028 TI - Alpha-2 interferon and 5-fluorouracil in advanced colorectal cancer. AB - A total of 21 untreated patients (5 males, 16 females; median age, 55 years; range, 28-72) with advanced measurable colorectal carcinoma were treated with an association of 5-fluorouracil (1000 mg/weekly) and alpha-2 interferon (three times a week s.c.: 6 x 10(6) U in the 1st month, 9 x 10(6) U in the 2nd month, 12 x 10(6) U in the 3rd month and then 18 x 10(6) U) until maximum response or progression of disease. Sites of disease involved liver in 10 patients, lung in 6, supraclavicular lymph nodes in 3, skin in 1, abdomen in 4, and vagina in 1 patient. Nine responses (42.8%) were documented (4 complete and 5 partial) with metastases confined to the liver, lung, nodes and skin. Median duration of response was 11 months (range, 4-17+) and median survival was 10 months (range, 2 17+). Side effects (fever, flu-like syndrome and leukopenia) required a dose reduction of 5-fluorouracil in 8 patients and interferon in 2 patients. PMID- 2205029 TI - [Malaria vaccines, a necessity for future control of malaria. Status and future perspectives]. AB - Traditional malaria control is in a crisis on account of chemo-resistance of Plasmodium falciparum and insecticide-resistance of the malaria mosquito. New ways to control malaria have been opened by the possibility of producing a vaccine. Several malaria proteins (e.g. CSP, gp195, Pf155/RESA, GLURP) have been sequenced and it has been shown that most of the proteins have repetitive units. Analyses of T- and B-cell epitopes show that T-cell epitopes are mainly localized to the non-conserved parts of the antigens. Repeated malaria infections, therefore, may be seen as a number of primary infections, which partly explains the very slow development of immunity to the parasite. The initial three vaccination experiments in humans did not succeed in inducing a complete protection of the individual but it showed that partial immunization is possible. PMID- 2205030 TI - [Use of micturition cystourethrography in evaluation of urinary incontinence in women]. AB - Miction cystourethrography (MCU) is an investigation of the conditions of suspension of the bladder. Assessment of the conditions of suspension has been employed by som urologists for 1) diagnosis of genuine stress incontinence (SI), 2) choice of operative procedure for SI and 3) assessment of the surgical result after operation for SI. It is generally agreed that MCU, as a routine method, does not contribute any important diagnostic information on account of the very low predictive values. Whether MCU can contribute information of significance in the choice of operative procedure for SI is still controversial. Recent investigations suggest that the suprapubic approach is more effective than vaginal procedures and that this should be preferred for SI, regardless of the type of possible suspension defect and the presence of slight to moderate cystocele. This reduces the significance of a meticulous radiological diagnosis. Whether large cystoceles should be operated upon vaginally and/or suprapubically is not yet elucidated but these are not indications for MCU as they can be diagnosed by gynaecological examination. Postoperative MCU has revealed poor correlation between cure and relief of a possible suspension defect. As MCU is a resource-demanding examination which may be difficult to interpret, it cannot be recommended as a routine in assessment of urinary incontinence in women. PMID- 2205031 TI - [Hemodynamic assessment of cerebrovascular circulation using transcranial Doppler ultrasound in patients with carotid stenosis]. AB - Transcranial Doppler-ultrasound (TCD) is a new non-invasive technique which renders continuous monitoring of the rate of flow in the major intracerebral arteries possible. The method appears, therefore, to be attractive for perioperative monitoring of patients submitted to operation on account of carotid stenosis. Seventeen patients were included in this preliminary investigation. These patients were submitted for thromboarterectomy of the internal carotid artery. Preoperatively the average flow rate (Vmean) in the ipsilateral medial cerebral artery measured at rest was 54 cm/second (range 34-94) as compared with 57 cm/second (range 32-86) in the contralateral medial cerebral artery. During occlusion, Vmean in the ipsilateral medial cerebral artery decreased momentarily, on an average 35% (p less than 0.001), and returned to the preoperative level after reopening of the internal carotid artery. Corresponding but no significant changes were observed in the pulsatile index. The preliminary experience suggests that TCD is scarcely useful as a diagnostic method in individual cases but that it is well suited for continuous monitoring of changes in cerebral circulating during surgery on the internal cerebral artery. Further assessment of the technique is necessary before the method can be employed routinely, mainly on account of the great interindividual scatter. PMID- 2205032 TI - [Inflammatory rheumatic diseases--a survey. Classification, diagnosis and treatment]. PMID- 2205033 TI - [Severe first dose reaction after administration of captopril to patients with carotid artery stenosis]. AB - During recent years, ACE inhibitors have been employed to an increasing extent in the long-term treatment of arterial hypertension. As part of the investigation of arterial hypertension, the captopril test, with administration of a small oral dose of captopril and registration of the blood pressure and pulse during the subsequent period, is employed. During this test, two cases of marked fall in blood pressure accompanied by symptoms of inadequate cerebral circulation were observed. Both of these patients were subsequently submitted to digital subtraction angiography of the vessels of the neck and both found to have unilateral stenosis of the carotid artery. It is concluded that, particularly in elderly hypertensive patients, ACE inhibitor treatment should always be initiated during controlled conditions. Stethoscopic examination of the carotid arteries should always be performed. PMID- 2205034 TI - [Women's experience of chorionic villi biopsy and its significance for the course of pregnancy. A qualitative study]. AB - Twenty-nine pregnant women and their families were questioned about how they experienced chorion villus biopsy in order to illustrate the significance of the test for the pregnancy. Semistructured interviews were carried out immediately after the test, one week later when the result was available and at ultrasonic scanning at the 18th-20th weeks of pregnancy, and these results form the basis for this study. One woman had a foetus with Down's syndrome. The remaining foetuses had normal chromosomes. The main interpretation of early foetal diagnosis and of a living foetus was positive. For the pregnant woman and her family, the main advantages were that the time of waiting for the result was reduced (as compared to the waiting time following amniocentesis) the psychological relief that the investigation can be performed early in pregnancy and that a possible termination could take place under full anaesthesia. PMID- 2205035 TI - [Sperm granulomata]. AB - Sperm granulomata are rare without prior surgical intervention but constitute a common complication of vasectomy and affect 35 and 42% with the conventional methods. Refertilizing and sperm quality are better in cases of sperm granulomata and, as opposed to previous assumptions, reduced fertility is not found in cases of sperm granulomata in patients with sperm antibodies. Fewer complaints are observed after open end vasectomy despite the particularly high incidence of sperm granulomata. Unfortunately, the literature does not appear to contain randomized investigations as guidelines for the choice of surgical method for vasectomy. PMID- 2205036 TI - [Hypothermia. Physiopathology, clinical picture and treatment]. AB - Hypothermia is defined as a lowering of core body temperature to 35 degrees C or below. Hypothermia may be advantageous in connexion with cardiac surgery or it may be fatal in connexion with accidental hypothermia. Accidental hypothermia is a problem which may be underestimated because of limited awareness. Severe hypothermia occurs when the body temperature falls below 28 degrees C. The patient may be unconscious, with such severely depressed vital signs that he appears to be dead. All such patients should undergo cardiopulmonary resuscitation in addition to rewarming, because reliable determination of death is nearly impossible without the restoration of adequate cardiovascular support, maintaining serum acid base balance, arterial oxygenation and intravascular volume levels within appropriate physiological ranges. Three controversial issues in connexion with treatment of the hypothermic patient are reviewed. These are correction of blood gas analyses, the phenomenon of afterdrop and cardiopulmonary resuscitation. PMID- 2205037 TI - [Fluconazole. A new antimycotic for systemic use]. PMID- 2205038 TI - [Neurogenic urinary incontinence: current treatment concepts]. AB - Neurogenic urinary tract dysfunction is characterized by inadequate voiding and urinary incontinence. The aim of therapy nowadays is adequate bladder emptying and control of urinary incontinence. Neurogenic urinary incontinence can be caused by (a) detrusor hyperreflexia, (b) sphincter hypo- or areflexia, (c) a combination of both, or also (d) detrusor hyporeflexia with consequent overlow incontinence. Based on a simple urodynamic classification the current treatment strategies are presented. (a) Detrusor hyperreflexia can be transformed into hypo or are-flexia pharmacologically with potent drugs now available. Bladder emptying then has to be assisted or can be achieved by intermittent catheterization. If conservative therapy fails, sacral posterior root rhizotomy together with implantation of a sacral anterior root stimulator (Brindley) is an alternative, especially for women. If the anatomical situation does not allow sacral deafferentation (e.g. in patients with myelomeningocele or sacral dysplasia) bladder augmentation is the method of choice: a detubularized segment of ileum will serve as an energy destroyer for the pressure resulting from uncontrollable detrusor contractions. In contrast to detrusor hyperreflexia (b) hypo- or areflexia of the sphincter cannot be influenced pharmacologically. Method of choice for restoration of urinary continence in these patients is the implantation of a hydraulic sphincter system (Scott); in this way urinary continence is achieved without creating outflow obstruction. The alternative is conventional colposuspension with maximal elevation of the bladder neck in order to create bladder neck outflow obstruction allowing the achievement of continence. In this situation intermittent catheterization is essential for bladder emptying (and can sometimes be difficult). If (c) detrusor hyperreflexia is combined with sphincter hypo- or areflexia, urinary incontinence is due to detrusor and sphincter dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2205039 TI - [Principles and indications of electrostimulation of the urinary bladder]. AB - Neurostimulation to restore the essential elements of lower urinary tract function is a very promising approach in the management of the neuropathic bladder. The goal of neurostimulation is to restore the three main functions of the lower urinary tract: the reservior capacity of the bladder, the sphincteric activity of the continence mechanism, and the ability of the bladder to evacuate completely. In extensive experimental studies conducted over the past 18 years, the physiological foundations of micturition and sphincteric control were investigated, which made the clinical application of neurostimulation in the management of the neurogenic bladder possible. In human studies, the essential experimental model of ventral root stimulation after dorsal rhizotomy and selective peripheral neurotomy proved to be the most successful. To date, over 220 patients have been treated, of whom 35 have spinal cord injury or severe neuropathy and received multiple sacral root implants. 25 of the 35 patients are evaluable, 15 (60%) of these achieved the three goals of the study: complete continence, restoration of reservoir function with adequate capacity, and voiding to neurostimulation with minimal residual urine or none. The remaining 185 patients with a variety of voiding dysfunctions classified under four main headings: 1) urge incontinence; 2) post-prostatectomy incontinence; 3) pelvic dysfunction syndrome in the male; 4) pelvic dysfunction syndrome in the female were treated by single electrode implantation in order to modulate spastic voiding dysfunction and pelvic floor activity. Success rates (improvement of 50% or more) were 72%, 38%, 46%, and 47% in the four groups, respectively. PMID- 2205040 TI - [Rheologic risk factors of apoplexy]. AB - There can be no doubt about the relevance of various established risk factors of stroke, which therefore will not be discussed. When trying to manipulate factors as hypertension, hyperlipoproteinemia and smoking, in most cases an improvement of the flow properties of blood can be observed. This makes flow properties at least very likely to trigger cerebral ischaemia and stroke. Furthermore there is increasing evidence, that single factors, contributing to a deterioration of blood rheology (i.e. haematocrit, fibrinogen, plasma viscosity, red cell rigidity) may be considered risk factors of apoplexie depending on the quality of interaction. There seem to exist positive correlations to the extent of atherosclerotic alterations of the vessel system. Blood viscositiy and red cell aggregation can be interpreted as the respective state of different pathologic profiles of blood rheology and thus might reach pathologic levels already before it is notified by single factors. In conclusion there is a good chance for blood viscosity and red cell aggregation to play an independent role as risk factors of apoplexie derived from cerebral ischaemia. PMID- 2205041 TI - [Differential diagnosis and prognosis of apoplexy]. AB - In world wide mortality statistics, cerebral circulatory disturbances still are the third most frequent cause of death. Especially strokes resulting from thrombosis occure more frequent with increasing age, while embolism and haemorrhage tend to occur in the younger age groups, too. In every case of stroke, whether of ischaemic origin or caused by haemorrhage, a complete diagnostic program is essential to clarify aetiology and pathogenesis and to establish an adequate therapeutic strategy and prognostic assessment. Factors, that influence the prognosis quo ad vitam et quo ad sanationem in a favourable way are: early onset of therapy (especially within the first six hours), adaequate therapy of risk factors and secondary complications, younger age and a favourable social situation. On the other hand, the prognosis is worsened by marked psychopathological changes in the initial stage, a combination of several risk factors and delayed onset of therapy. PMID- 2205042 TI - Serum levels of gastrin, insulin and glucagon as possible factors of anorexia in pigs infected once with Ascaris suum. AB - In order to determine possible mediators for development of anorexia in pigs infected with Ascaris suum, serum levels of gastrin, insulin and glucagon were measured. After a single high oral dose of 100,000-200,000 embryonated eggs the serum levels of gastrin and insulin in the infected pigs did not significantly differ from those in controls. Serum glucagon levels in the infected groups, however, were lower than those in controls and the difference was more evident 24 days postinoculation and later. PMID- 2205043 TI - [The time factor in multistage carcinogenesis]. PMID- 2205044 TI - [The cellular localization of the fertility alpha 2-microglobulin in tumors of the reproductive system]. AB - Seventy-five samples of human tumors were examined immunohistochemically for fertility alpha-2-microglobulin also known as progesterone-associated protein of the endometrium. The protein was detected in 35.7% (5 of 14) endometrial cancer samples and in 20% (2 of 10) of ovarian malignancies. Tumors of the stomach, colon, breast, lung and some other sites failed to reveal the antigen with the exception of a single case of pulmonary adenocarcinoma which showed the ectopic expression of the protein. Fertility alpha-2-microglobulin is stage-specific tissue marker of the endometrium. It is expressed at the final stage of cell differentiation and is partially lost in cancer. PMID- 2205045 TI - [The classification of food poisonings]. PMID- 2205046 TI - [The pluralism of scientific concepts and the development of the science of nutrition]. PMID- 2205047 TI - [The Ukrainian State Institute of Public Health--the first comprehensive social hygiene institution in the Ukrainian SSR]. PMID- 2205048 TI - [A case of Klebsiella sepsis with an atypical course]. PMID- 2205049 TI - [Gastroesophageal reflux in patients with chronic nonspecific lung diseases]. AB - The author examined 30 patients with clinical symptoms of gastroesophageal reflux. The patients suffered of bronchial asthma (19) and chronic obstructive bronchitis (11). Intraesophageal and intragastric proteolysis with subsequent digestion of the protein substrate in solutions with different concentration of hydrogen ions (pH 1.68 and 8.15). Gastroesophageal reflux was observed in 25 and duodenogastroesophageal in 16 patients. The gastric and duodenal contents reached the upper portions of the esophagus in 14 of the 30 patients. The obtained findings indicate frequent effects of proteases on the bronchi. PMID- 2205050 TI - [The differentiation of A-insulocytes in the human embryonic pancreas]. AB - In the differentiation of A-insulocytes in the human pancreas the following stages were distinguished: nondifferentiated cells of the epithelial anlage (5-6 weeks)--cell of primary duct (5-6 weeks)--duct cell containing lumps of secretory material (7-8 weeks)--cell precursor of A-insulocyte containing immature secretory granules (7-8 weeks)--A-insulocyte containing separate mature granules (9-10 weeks)--mature A-insulocyte (9-10 weeks). All this is accompanied by appearance at the 7-8 week of glucagon in the pancreatic tissue (76.20 +/- 17.28 ng/mg of wet tissue). The content of glucagon rises in 9-10 weeks 8.3 times. PMID- 2205051 TI - [The effect of hormones on the activity of aspartate and alanine aminotransferases (a review of the literature)]. PMID- 2205052 TI - [The immunomodulating action of the seminal plasma (a review of the literature)]. PMID- 2205053 TI - [Dopplerographic study of the internal carotid and vertebral arteries in middle aged and elderly patients with a chronic cervical pain syndrome]. AB - The method of discriminant analysis was used to treat data of ultrasound dopplerographic examination of the major arteries in the neck in 67 patients of middle and old age with neurodystrophic manifestations of cervical osteochondrosis and pain syndrome of different intensity. Most informative for distinguishing these groups independent of the age was the systolic linear pulse blood flow velocity in the right vertebral artery during rest and in the vertebral arteries during short-time compression of the right common carotid artery. PMID- 2205058 TI - [Pathophysiology of acute pancreatitis]. AB - Recent experiments in different animal models of acute pancreatitis have improved our understanding of the pathophysiology of this disease. The present review discusses the individual steps and mechanisms and puts them into a pathophysiologic concept for the two most important forms of acute pancreatitis (alcoholic and biliary form). In biliary acute pancreatitis a temporary occlusion of the common channel by impacted stones may be followed by a reflux into the pancreatic duct. This reflux results in an increase of ductal permeability and extravasation of cytotoxic agents into the surrounding tissue. As consequences, disturbances of compartimentation and faulty activation of enzymes occur in pancreatic cells. Long-term cellular damage, obstruction of pancreatic ducts and increase of ductal permeability with leakage of noxious agents play a substantial role in pathophysiology of alcoholic pancreatitis. Sustained abuse of alcohol usually leads to chronic pancreatitis. Additional, as yet unknown factors are necessary to induce acute alcoholic pancreatitis. Following its initiation by different etiological sources, pathophysiology of acute pancreatitis may take a similar course. Digestive enzymes are activated and set free into intracellular, intraductal and interstitial spaces. Trypsin as the trigger-enzyme of activation cascade is thought to play a major role. In addition, lipolytic enzymes may be involved in the pathophysiologic process. Phospholipase A is known to release lysolecithin which causes membrane damage. Recent studies indicate that the release of fatty acids by lipase causes acinar cell necrosis. New insights into the pathophysiology may lead to a rational and more successful therapy of acute pancreatitis. PMID- 2205055 TI - Hypothalamic neuronal responses to cytokines. AB - Fever has been extensively studied in the past few decades. The hypothesis that hypothalamic thermosensitive neurons play a major role in both normal thermoregulation and in fever production and lysis has particularly helped to advance our understanding of the neuronal mechanisms underlying the response to pyrogens. Furthermore, new data in the study of host defense responses induced by pyrogenic cytokines such as interleukin 1, interferon alpha 2, tumor necrosis factor alpha, and interleukin 6 have demonstrated that those factors have multiple, yet coordinated, regulatory activities in the central nervous system, so that our understanding of the role of the brain in the activity of these agents requires a new perspective and dimension. Thus, recent evidence from our laboratory indicates that blood-borne cytokines may be detected in the organum vasculosum laminae terminalis and transduced there into neuronal signals. Such signals may then affect distinct, but partially overlapping, sets of neuronal systems in the preoptic area of the anterior hypothalamus, mediating directly and/or indirectly the array of various host defense responses characteristic of infection that are thought to be induced by blood-borne cytokines. PMID- 2205054 TI - Neuromodulative actions of cytokines. AB - Interleukin 1, interferon alpha 2, and tumor necrosis factor alpha are cytokines that centrally mediate various reactions typical of the host defense responses to infection. The preoptic-anterior hypothalamus is an important, but not exclusive, integrative and controlling region for several of these effects. Although these cytokines display some common functional activities (e.g., pyrogenicity, somnogenicity), the characteristics of the responses they induce are different. Their effects, moreover, can be evoked or suppressed selectively, indicating that the neuronal substrates and/or neuromodulators used are distinct, each possessing discrete but partially overlapping sensory combinations. Nevertheless, it is not yet obvious how these systems are organized and integrated in host defense. It is also unclear whether these cytokines are elaborated peripherally and gain access to the brain or whether they are induced centrally. The available data suggest that circulating cytokines probably do not penetrate the brain but may activate elements in the organum vasculosum laminae terminalis. This site appears to be critically important for the production of the centrally mediated effects of blood-borne cytokines; it is speculated that the cytokines evoke there local signals that transduce their message; serotonin may be linked to these signals. PMID- 2205056 TI - Somnogenic cytokines and models concerning their effects on sleep. AB - All the sleep-promoting substances currently identified also have other biological activities. Despite years of effort, a single specific central nervous system sleep center has not been described. These observations led us to propose a biochemical model of a sleep activational system in which the effects of several sleep factors are integrated into a regulatory scheme. These sleep factors interact by altering the metabolism, production, or activity of each other and thereby result in multiple feedback loops. This web of interactions leads to sleep stability in that minor challenges to the system will not greatly alter sleep. The system, however, is responsive to strong perturbations, such as sleep deprivation and infectious disease. The sleep-promoting effects of cytokines and their interactions with prostaglandins and the neuroendocrine system are used to illustrate the functioning of a part of the sleep activational system under normal conditions and during infectious disease. Although the actions of individuals sleep factors are not specific to sleep, their interactions at various levels of the neuraxis can mediate a specific sleep response. Such a system would also be responsive to the autonomic and environmental parameters that alter sleep. PMID- 2205059 TI - [Human immunodeficiency virus (HIV): a review]. AB - Since its discovery in 1983, a lot of knowledge about the human immunodeficiency virus (HIV) has been accumulated. Our paper gives a brief survey on what is known at present about the structure, molecular biology, and the cell tropism of this virus. We discuss its relationship to other lentiviruses as well as its possible origin; in addition, we refer to the immune response to HIV and its interactions with the infected host. We also briefly summarize the difficulties encountered in the attempts to produce a vaccine against HIV and highlight some promising approaches in the development of such a vaccine. PMID- 2205057 TI - Modulation of host defense by the neuropeptide alpha-MSH. AB - alpha-melanocyte stimulating hormone (alpha-MSH), a peptide that occurs within the brain, the circulation, and other body sites, is a potent antipyretic agent when given centrally or peripherally. The peptide likewise inhibits inflammation and aspects of the acute-phase response. The combined evidence suggests that alpha-MSH molecules act as natural modulators of host reactions by antagonizing the central and peripheral actions of cytokines. PMID- 2205060 TI - [Detection of HIV infection by serologic procedures]. AB - We briefly describe the principal techniques of antigen detection and discuss the pros and cons of routine screening and conformation assays. Regarding the differentiation of HIV 1 and HIV 2 infection, synthetic peptides corresponding to the antigenic epitopes of gp36 (HIV 2) and gp41 (HIV 1) yielded the best results. Commercially available antigen tests are relatively insensitive. New techniques, such as the polymerase chain reaction, allow the dedection of viral DNA in one infected cell out of 100,000 non-infected cells. However, since these methods are based on nucleic acid probes, they are rather laborious and cannot replace antibody tests; but they may be of use for early identification of HIV-infected infants or for the confirmation of the acute phase of the infection (CDCI). With regard to early prognosis--i.e. up to 2 years before the development of clinical symptoms__the following markers have been found useful: neopterine, beta-2 microglobulin, the lymphocyte subsets CD4, CD8, Leu2+7+, activated T-cells, as well as the decrease of antibodies against p31, p24 and p17. PMID- 2205061 TI - [Skin manifestations in patients with HIV infection]. AB - Cutaneous manifestations are common in patients with HIV infection and mainly due to the immunodeficiency. In the initial stage of HIV infection, we frequently observe a rash of macular lesions. During the asymptomatic phase, the patients may typically show the following skin diseases: seborrhoic dermatitis, acneiform folliculitis, persistent herpes simplex, and infections with the human papilloma virus. In ARC and AIDS patients, 3 groups of skin disorders are found: cutaneous infections, skin tumors, and other mixed skin diseases. Herpes simplex and herpes zoster may develop into ulcerating and necrotising forms especially in patients with advanced immunodeficiency. The most frequent skin tumors in AIDS patients are the disseminated Kaposi's sarcoma and non-Hodgkin's lymphoma. More than 50% of the AIDS patients treated with trimethoprim/sulfamethoxazole developed a severe drug eruption. African and Caribbean patients with AIDS frequently suffer from pruritic skin lesions, the pathogenesis of which is not known. Aside from these cutaneous manifestations, a variety of other skin disorders have been reported in patients with HIV infection, ARC, or AIDS; future research will furnish definite proof whether they are correlated with HIV infection. PMID- 2205062 TI - [AIDS--mucous membrane manifestations]. AB - In the course of the infection with the human immunodeficiency virus (HIV), we frequently observe disorders of the mucous membranes and, occasionally, they present the first manifestation of HIV-induced immunodeficiency. Like in other organs, opportunistic infections and malignant tumors prevail as a result of the impaired immune system. Opportunistic infections are characterized by frequency (candidiasis), aggressive expansion, persistence, frequent recurrences, and resistance to therapy (gingivitis, parodontitis, herpes simplex, warts). Oral hairy leucoplakia is considered a specific lesion of HIV infection. Malignant tumors, such as Kaposi's sarcoma, non-Hodgkin's lymphoma, and squamous cell carcinoma, may cause marked morbidity in AIDS patients; occasionally, the clinical picture of Kaposi's sarcoma and non-Hodgkin's lymphoma is rather uncharacteristic. Other manifestations on the mucous membranes may arise in association with systemic reactions, such as drug eruptions, thrombocytopenic purpura, or acute HIV infection. The etiology of still other lesions of the mucous membranes (e.g. chronic recurrent ulcers, xerostomia, disorders of pigmentation) is incompletely understood. The awareness of these disorders of the mucous membranes in HIV infection is of diagnostic, therapeutic and epidemiological importance. PMID- 2205063 TI - [Histology of the skin and mucous membrane manifestations of AIDS]. AB - The dermatopathologist must be aware of the wide spectrum of non-specific cutaneous manifestations, cutaneous infections and skin tumors associated with AIDS. We present the histological criteria essential for the diagnosis of early Kaposi's sarcoma, its differential diagnosis including epithelioid angiomatosis, as well as the diagnosis of oral hairy leucoplakia. PMID- 2205064 TI - [AIDS therapy]. AB - Therapy of AIDS comprises two aspects: (1) causative therapy, directed against HIV, and (2) symptomatic therapy of opportunistic infections and malignancies. The best results regarding antiretroviral therapy - both in vitro and in vivo - have been obtained, so far, with inhibitors of reverse transcriptase. We discuss the mechanism of action, the efficacy, and the side effects of AZT, a nucleoside analogue, and comment on combined therapies with acyclovir and immunomodulators. We report on the therapy of the most frequent opportunistic infection - i.e. Pneumocystis carinii pneumonia - with sulfamethoxazole/trimethoprim and pentamidine as well as the chemoprophylaxis of this disease. During the last few years, important progress has been made in the field of antiviral chemotherapy (HSV, CMV, VZV) and the therapy of gastrointestinal infections. Moreover, the therapy of Kaposi's sarcoma associated with AIDS and that of non-Hodgkin's lymphoma has been established by now. PMID- 2205065 TI - [Possibilities and limits of echocardiography]. AB - Echocardiographic imaging (two-dimensional and M-mode technique) with extrathoracal transducer positioning is, in addition to other echocardiographic methods (transesophageal scanning, contrast-enhanced echocardiography, Doppler ultrasound), an important diagnostic tool for determining the morphology, function, and hemodynamics of the heart and the large vessels. It is a safe diagnostic procedure and is, therefore, an important basis for further cardiac evaluation by invasive techniques. Echocardiography in general is not only of high diagnostic value for the noninvasive evaluation of cardiac disorders, but it is also often the basis for an adequate therapeutic procedure, as well as for evaluation of clinical follow-up, prognosis, and exercise performance of the cardiac patient. PMID- 2205066 TI - [Children of alcoholic patients]. PMID- 2205068 TI - [Including pulsed Doppler ultrasound study in the obstetric management of at-risk pregnancies]. AB - Using the results of 2,130 assessments with pulsed wave Doppler-ultrasound we established an indication catalogue which reflect the availability in cases of high specificity of the method. The paper shows the modus of fetal monitoring by inclusion of the other obstetrical investigations in consequence of the Doppler assessment and the frequency of repetition of it. PMID- 2205067 TI - [Perioperative preventive antibiotic administration in hysterectomy?]. PMID- 2205069 TI - [Stress caused by sports in pregnancy]. AB - The wide adaptation range of the circulatory system, the respiratory system, and the metabolism of the female organism during pregnancy permits utilization of many positive effects of physical exercise for optimal health and wellbeing. Hitherto physically inactive pregnant women should be intensively motivated and advised, while women who are already physically active regularly should be advised to combine planned pregnancies with an optimally step-by-step reduction in training. After an uncomplicated delivery, and dependent on a normal uterus involution and lactation, a gradual adaptation to a renewed training program can be recommended. The advantages of physical exercise during pregnancy were analysed in relation to possibly dangerous complications during intensive training periods. The most important contraindications are described. The authors emphasize the increasing importance of cooperation between the Pregnancy Health Service and the Sports Medicine Service for optimal medical guidance of physically active pregnant women. PMID- 2205070 TI - [Evaluation of the central hemodynamics of the fetus using pulsed Doppler ultrasound]. AB - Using pulsed Doppler, blood flow in the cerebral arteries was measured to assess the fetal central circulation. The Pulsatility-Index (PI) was calculated as a qualitative parameter of flow velocity waveforms. In 418 normal singleton pregnancies we performed 558 measurements between the 27th and 40th week of gestation to get normal range values of the PI. The curve shows a small decrease in the observed interval. In cases of an intrauterine hypoxia the resistance of the central vessels decrease to render the distribution of the fetal blood volume. The result of this is a centralisation of the fetal circulation. 131 high risk pregnancies were investigated and in 21 cases such a centralisation was registered. The fetal outcome of these fetuses was significantly worse compared with fetuses having a normal central flow resistance. We found for example a higher rate of caesarean sections because of fetal distress when the Pulsatility Index was below the 5th percentile. The sensitivity of the method in prediction caesarean section for fetal distress was 59.3%, the specifity 95.3%. PMID- 2205071 TI - [Perinatal imaging diagnosis in twin pregnancies with humanus amorphus]. AB - The humanus amorphus or acardiac twin is a very rare anomaly found only in monocygotic multiple pregnancies. In 8 twin pregnancies observed from 1977 to 1988 at the Charite-Hospital the findings of perinatal imaging diagnostics (sonography, amniofetrography, postnatal radiography) have been presented. For the prenatal diagnosis, especially for continuous prenatal control in these high risk pregnancies, sonography seems to be the suitable method. However, an exact classification and morphological description of such monstrosities will be possible only by postnatal radiography (eventually in combination with a transumbilical angiography). Six ouf of eight cases were classified as an acephalous type, and two as an acardius anceps fetus. PMID- 2205073 TI - Medicare and nurse anesthesia education. PMID- 2205072 TI - [Early detection of diabetes in pregnancy--a factor for reducing perinatal mortality and morbidity]. AB - At present the main problem in gestational diabetes (GDM) is that only less than 10% of the pregnant diabetics could be diagnosed and accordingly treated. Analysing 101 cases of pregnant diabetics we refer to the incidence of peripartal and perinatal complications. The treatment with insulin was necessary to be applied on 70 of the patients (69.3%) in order to achieve normal glucose levels (between 3.3 and 6.6 mmol/l). If the metabolic complications are determined and treated in a later phase of pregnancy, there is a higher rate of complications (toxemias 29.7%, premature labor 21.8%, caesarean section 23.8%, perinatal mortality 2.9%, congenital anomalies 5.9% and the likelihood of large for gestational age babies 32.7%). Improvement of such results, which can be obtained in optimally treated insulin - dependent pregnants, is possible only by more early determination of all carbohydrate tolerance disturbances in pregnancy. This proposed diabetic screening is generally required in any pregnant woman with a history diabetes, obesity greater than or equal to 20%, age greater than or equal to 30 years and glucosuria. A gestational diabetes is to be considered into consideration if in a 50 g-oral-glucose-tolerance-test (50 g - OGTT) 2 values exceed normal limits (fasting level 5.55 mmol/l, 60 minutes level 8.88 mmol/l and 120 minutes level 7.22 mmol/l). Further observation of these patients has to be continued centrally. PMID- 2205074 TI - Historical perspectives on anesthetic-related cardiac arrest and resuscitation. AB - Contemporary interest in resuscitation was historically related to anesthetic death. Primitive techniques of anesthetic administration, loss of airway control, and psychologically influenced sudden death contributed to unanticipated respiratory and cardiac arrest. Airway obstruction has remained the principal factor in asphyxial death, necessitating crucial preservation of respiratory function during induction of anesthesia. Early, disorganized overdose and arrest interventions included: application of cold water, manual artificial respiration, heat, friction and galvanic battery application. Cardiopulmonary resuscitation, after years of research and experimentation became an integrated plan of attack: mouth-to-mouth ventilation and maneuvers eliminating pharyngeal obstruction were proven effective; internal and external cardiac massage was incorporated and definitive drug therapy began with epinephrine, strychnine, caffeine, carbon dioxide, amyl nitrate, coramine, metrazol and procaine. Defibrillation proved electricity converted ventricular fibrillation to normal sinus rhythm. Significant lethality still occurs from anesthetic-induced cardiac arrest, despite technological advances. Causes of operating room cardiac arrests are numerous and include sudden death syndrome. Constant vigilance distinguishes variable patient response. Immediate recognition and coordinated intervention assures success. PMID- 2205075 TI - AANA journal course: new technologies in anesthesia: update for nurse anesthetists--lasers. AB - The common use of the laser in many specialty areas has challenged the anesthetist to possess more than a cursory knowledge of laser function and safety. The unique property of laser light and its effect on tissues presents unique safety considerations for patients and personnel. The protection of flammable materials, selection of the least flammable gas mixture and determination of the most appropriate anesthetic technique all work in concert to provide a beneficial outcome for everyone. This course will discuss principles of laser technology, safety for patients and personnel and precautions in anesthetic management. PMID- 2205077 TI - Homicide in the Nordic countries. AB - This article reviews and assesses previous studies of homicide in the Nordic countries and compares the main findings with those from other countries. In spite of the relative sparsity of data, the nature of the available information allows a reasonably reliable comparison to be made between different Nordic countries. Although findings from separate studies vary somewhat, some general trends have been noticed and seem to apply to most of the countries in question: in particular, changes that have occurred over the last 2 decades. Thus, all the Nordic countries have experienced an increase in homicide incidence during this period, and with some notable exceptions, this increase has been quite drastic. Certain other trends have been observed, such as the prominent role of alcoholism and drug abuse in homicide offences, as well as the relative increase in nondomestic offences. Homicide followed by suicide has decreased proportionately among males, whereas this trend has not occurred to the same extent among females, who are more frequently involved in domestic homicide. Methods of homicide have also varied somewhat during the last few decades. The case of homicide in Greenland is discussed separately in view of its special circumstances. Studies dealing with the various psychiatric and mental health problems related to homicide in the Nordic countries are discussed and a hypothesis is offered about possible sociocultural factors, in particular alcohol and drug abuse, that seem to be important. PMID- 2205076 TI - Heterogeneity of dystrophin expression in patients with Duchenne and Becker muscular dystrophy. AB - This report documents the results of an integrated biochemical and immunocytochemical investigation into the expression of dystrophin (the protein product of the Duchenne muscular dystrophy gene) in muscle biopsies from 226 patients. It is the first study in which dystrophin has been analysed on blots and on tissue sections in such a large number of patients using the same (monoclonal) antibody. The 140 patients with Xp21 muscular dystrophy who were included in this study represent a continuous spectrum of disease severity and this range was reflected in the heterogeneity of dystrophin expression which was observed with respect to abundance, size and the pattern of tissue localisation. Approximately 40% of biopsies obtained from patients diagnosed as having Duchenne muscular dystrophy (DMD) contained isolated clearly positive fibres and a further 20% had very weak labelling on a large number of fibres. Biopsies from patients with Becker muscular dystrophy (BMD) showed labelling patterns which varied from weak labelling on the majority of fibres to clear labelling on all fibres. Typically, however, there was inter- and intra-fibre variation in labelling intensity. Approximately 85% of the 52 BMD and 54 DMD patients who had unequivocal labelling on blots demonstrated a protein of abnormal size. The remaining 15% had a protein of normal size but reduced abundance. Overall, the estimated abundance of dystrophin correlated well with clinical assessments of the disease severity expressed in patients. We conclude that dystrophin analysis is an essential and dependable technique for the differential diagnosis of patients with Xp21 muscular dystrophy. PMID- 2205078 TI - Fibrinolytic activity after subarachnoid haemorrhage and the effect of tranexamic acid. AB - Seventy-four patients with recent subarachnoid haemorrhage were randomly allocated to placebo or tranexamic acid treatment. Fibrinolytic activity in the blood and cerebrospinal fluid was assessed before treatment, one week later and two weeks later. The natural history of fibrinolysis following subarachnoid haemorrhage was obtained from analysis of the placebo group. Following subarachnoid haemorrhage, fibrin degradation products and plasminogen activity in the cerebrospinal fluid were elevated. Subsequently, fibrin degradation products in the cerebrospinal fluid fell progressively over the following 2 weeks. Changes in cerebrospinal fluid plasminogen activity correlated with those of blood plasminogen activity. Complications such as rebleeding, hydrocephalus or cerebral thrombosis could not be predicted from analysis of fibrinolytic activity. Tranexamic acid treatment resulted in a reduction in cerebrospinal fluid and blood plasminogen activity. The relevance of fibrinolysis in cerebrospinal fluid and blood to the management of subarachnoid haemorrhage is discussed. PMID- 2205079 TI - Rathke's cleft cyst: computed tomographic scan and magnetic resonance imaging. AB - Three patients with histologically proved Rathke's cleft cysts (RCCs) were evaluated with magnetic resonance imaging (MRI) and computed tomographic (CT) scan. Thirteen cases reported in the previous literature were also reviewed to evaluate the MRI features of RCCs and to compare them with CT features. The RCCs had various patterns of signal intensities on T 1-weighted and T 2-weighted MRI. The cysts were well-circumscribed and mainly in the sella turcica extending to the suprasellar cistern with minimal mass effect. Ten of sixteen cases had homogeneous cysts, and six had heterogeneous cysts. The CT scans showed the cysts as low or isodensity, well-demarcated lesions in the sella, that did not enhance with a few exceptions in which a thin ring enhancement was seen. MRI is superior to CT in the evaluation of the RCC, and is particularly useful in surgical planning, although MRI has a limitation on the specific, analytic description of the cyst contents. PMID- 2205080 TI - Production of bacterial thermostable alpha-amylase by solid-state fermentation: a potential tool for achieving economy in enzyme production and starch hydrolysis. PMID- 2205081 TI - Microbial levan. AB - Levans are natural polymers of the sugar fructose found in many plants and microbial products. Like dextrans, they are formed as an undesirable by-product of sugar juice processing. On the other hand, levans, which can only be produced from sucrose, have potential industrial applications as thickeners and encapsulating agents and could provide additional, valuable products from sugarcane juice. A strain of B. polymyxa (NRRL B-18475) produced a high yield of polysaccharide when grown on sucrose solution. Hydrolysis and subsequent analyses showed the product to consist entirely of D-fructose. 13C-NMR and methylation analyses indicated the products to be a beta(2----6)-linked polymer of fructose, with 12% branching. The polysaccharide has a Mr of approximately 2 million and is readily soluble in water. Levan has not been utilized, but if developed, could be useful in food and other industrial applications. PMID- 2205082 TI - Review and evaluation of the effects of xenobiotic chemicals on microorganisms in soil. PMID- 2205083 TI - Disclosure requirements for biological materials in patent law. PMID- 2205084 TI - Methods for studying bacterial gene transfer in soil by conjugation and transduction. PMID- 2205085 TI - Study of subcutaneous fat. AB - The main goal of this article is to demonstrate that biochemically, metabolically, histologically, embryologically, and anatomically there are two totally different types of subcutaneous fat. This fact has clinical and surgical consequences including the concept of dynamic and surface anatomy. PMID- 2205086 TI - The development of aesthetic facial surgery in Japan: as seen through a study of Japanese pictorial art. AB - A study of pictorial art in Japan reveals a basic concept of beauty which is very much related to the development of aesthetic surgery for the Japanese face. The eyes, nose, and mouth in a round-to-oval face are traditionally expressed in a unique manner that is based on the Buddhist ideas of harmony and universality. The common facial characteristics of the Japanese were idealized in a manner that was best seen in the oblique view. The key to effective aesthetic surgery for such facial features is suggested in the author's ideas for enhancing facial expression and individuality. This can be seen in the double-eyelid operation and augmentation rhinoplasty, which are the two asthetic surgery procedures that are more popular in Japan than in the West. PMID- 2205087 TI - [A case of metastatic renal tumor: review of 74 cases reported in Japan]. AB - A 76-year-old man, who had undergone surgery for lung cancer, was referred to our department for further examination for left renal mass. Exploration was done through a transperitoneal approach and the left kidney was removed. A metastatic renal tumor originating from a pulmonary squamous cell carcinoma was diagnosed histologically. There have been 73 reported cases with metastatic renal tumor in Japanese literature and we reviewed the pathogenesis and treatment of this rare entity. PMID- 2205089 TI - [Leiomyoma of urinary bladder: report of a case]. AB - A case of leiomyoma of the urinary bladder in a 46-year-old woman is reported. The patient was referred to us because of incidental finding of a mass in the bladder. Cystoscopy revealed a protruding tumor covered with normal-appearing urothelium on the right posterior wall of the bladder. The tumor was well demarcated from adjacent organs on echography and computed tomographic scan. Transurethral biopsy revealed a bladder leiomyoma. Partial cystectomy was performed. The patient is now apparently free of disease 7 months after the operation. PMID- 2205090 TI - Plasma glucose, ketone bodies, insulin, glucagon and enteroglucagon in cows: diurnal variations related to ketone levels before feeding and to the ketogenic effects of feeds. AB - Ingestions of a moderately ketogenic silage twice daily were followed by transient increments in plasma insulin and ketone bodies and decreases in plasma glucose. Ketone bodies and glucose were negatively correlated throughout the day, but the insulin elevations culminated before the maximal effects on ketone bodies and glucose were established. Cows with varying glucose levels before morning feeding reacted to a highly ketogenic silage by decreasing their glucose level uniformly to about 3 mmol/l, in spite of a widely varying feeding-induced insulin increment. Hay-feeding caused insulin increments of the same magnitude as silage feeding, but the glucose decrease and the ketone increment was much smaller. The results indicate some direct action of ketone bodies on blood sugar regulation, in addition to effects mediated by insulin. The role of ketone bodies as the insulinotropic factor was not confirmed. The insulin level after feeding seems to be determined by the carbohydrate status of the animal before feeding. No significant changes in plasma glucagon were observed after feeding, and no consistent differences in plasma levels of this hormone were found when non ketonemic, ketonemic, and clinically ketotic cows were compared. The plasma level of enteroglucagon (GLI) was positively correlated to the relative amount of concentrates consumed, but no relation to plasma glucose was found. PMID- 2205088 TI - [Renal pelvic tumor in chronic renal failure: report of a case]. AB - A 44-year-old female was admitted because of gross hematuria six years after beginning hemodialysis for chronic renal failure. There was a past history of hematuria one year before admission. Retrograde pyelography, computed tomographic scan and angiography had been performed, and a probable malignant tumor of left renal pelvis had been found in 1986. We recommended surgery at the time, but she refused treatment and was followed up. On June 22, 1987, the patient had a second attack of gross hematuria resulting in bladder tamponade, and hematuria from the left ureteric orifice was confirmed at cystoscopy. Ultrasound showed left obstructive nephropathy. Left nephrectomy was performed because of the presumptive diagnosis of malignant tumor. The histological diagnosis was transitional cell carcinoma of the left renal pelvis. Two courses of M-VAC (methotiexate, vinblastine, adriamycin and cisplatin) chemotherapy were accordingly given postoperatively. The incidence of renal pelvic tumor and its chemotherapy in patients with chronic renal failure are discussed. PMID- 2205091 TI - Phagocytosis induced by yeast cells in canine granulocytes: a methodological study. AB - A phagocytic function assay of canine granulocytes was established. This method allows the proportion of active granulocytes to be estimated as well as the number of adhered and ingested yeast cells. The influence of different factors on phagocytosis was studied. Temperature variation within the interval 36-41 degrees C did not affect phagocytosis. The incubation time for optimal phagocytosis of yeast cells was 35 min. The opsonization procedure giving the optimal phagocytosis was purified IgG and serum together. PMID- 2205092 TI - Medicare physicians reimbursement. PMID- 2205093 TI - Misleading subgroup analyses in GISSI. PMID- 2205094 TI - In vitro endocytosis of benign and malignant human bone marrow plasma cells. AB - We report ultrastructural evidence of the phagocytic potential of plasma cells and myeloma cells. The incubation of plasma cells and myeloma cells in vitro with horseradish peroxidase (HRP) and cationized ferritin (CF) allows the tracing of fluid-phase and receptor-mediated pathways. Surface-bound ligands (CF) and solutes (HRP) taken up in primary pinocytic vesicles are internalized to the endosomal compartment. After 1 hr of incubation, CF was found not only in plasma cells but also in myeloma cells. Reaction products of HRP were observed only in myeloma cells. In myeloma cells, however, HRP was located only in the lysosomal system, whereas CF was present within membrane cisternae as well as within lysosomes. These myeloma cells morphologically produced interleukin-6 (IL-6). PMID- 2205095 TI - Acquired von Willebrand disease in multiple myeloma secondary to absorption of von Willebrand factor by plasma cells. AB - A case of acquired von Willebrand disease (AvWD) associated with an IgA lambda multiple myeloma is reported. No form of inhibitor could be detected. SDS-agarose gel electrophoresis patterns of von Willebrand factor (vWF) both in plasma and platelet lysates were normal but a decrease in all-sized multimers with a type IA pattern was seen. After 1-deamino-8-D arginine vasopressin (DDAVP) infusion, vWF multimers larger than those seen in the resting state appeared in patient plasma, which were progressively cleared. Indirect immunofluorescence studies with a monoclonal antibody to vWF showed that vWF was selectively absorbed into myelomatous cells. This is the first case of AvWD associated with multiple myeloma resulting from the selective absorption of vWF into abnormal plasma cells. This feature established a new pathophysiological mechanism of AvWD in multiple myeloma and probably in other lymphoproliferative diseases. PMID- 2205096 TI - Detection of interleukin-6 (IL-6) in human bone marrow myeloma cells by light and electron microscopy. AB - We used an Avidin-Biotin peroxidase complex (ABC) immunoperoxidase technique to evaluate the localization of IL-6 of human bone marrow cells in multiple myeloma (MM). The cellular distribution of IL-6 was determined at light and electron microscopic levels. The author's study indicated that cytoplasmic IL-6 was detected only in the myeloma cells of bone marrow cells. Immunoelectron microscopic (immuno-EM) study showed positive reactivity mainly in the perinuclear space (PNS), well-developed rough endoplasmic reticulum (RER), and Golgi area. PMID- 2205097 TI - Patterns of complement activation in idiopathic membranoproliferative glomerulonephritis, types I, II, and III. AB - Complement profiles on 22 hypocomplementemic patients with membranoproliferative glomerulonephritis (MPGN) type I, on 11 with MPGN II, and on 16 with MPGN III, gave evidence that the nephritic factor of the amplification loop (NFa) is responsible for the hypocomplementemia in MPGN II and the nephritic factor of the terminal pathway (NFt) for the hypocomplementemia in MPGN III. In contrast, in MPGN I, there was evidence for three complement-activating modalities, NFa, NFt, and immune complexes. As a result, four different patterns of complement activation were seen. NFa, found in MPGN II, produces a complement profile characterized mainly by C3 depression. In addition, four of seven (57%) severely hypocomplementemic MPGN II patients (C3 less than 30 mg/dL) had slightly depressed levels of factor B, and one of seven (14%) of properdin, but in all the C5 concentration was normal. In contrast, all eight severely hypocomplementemic patients with MPGN II had depressed C5 and properdin levels, and six of eight (75%) depressed levels of C6, C7, and/or C9. Of eight MPGN III patients with moderate hypocomplementemia, 50% had depressed C5 and properdin levels and the remainder, depressed C3 only. This spectrum of profiles is most likely produced by varying concentrations of NFt. In MPGN I, nine of 23 (39%) had a profile indicating only classical pathway activation; seven of 23 (39%), a pattern compatible with NFt alone; four of 23 (9%), evidence for both classical pathway activation and NFt; and three of 23 (13%), a pattern compatible with NFa. The unique multifactorial origin of the hypocomplementemia in MPGN I, often giving evidence of classical pathway activation, together with previously reported differences in glomerular morphology and clinical features at onset, makes it distinct from MPGN III. Depressed C8 levels were found to some extent in all hypocomplementemic states. The levels were uncommonly depressed in patients with NFa, most markedly depressed with NFt, and moderately reduced with classical pathway activation. The cause is not known. Diagnostically, profiles showing classical pathway activation and low levels of C6, C7, and/or C9 are specific for MPGN I. Those showing only classical activation are likewise diagnostic of MPGN I if systemic lupus erythematosus (SLE) and chronic bacteremia are ruled out. PMID- 2205098 TI - Utility of radioisotopic filtration markers in chronic renal insufficiency: simultaneous comparison of 125I-iothalamate, 169Yb-DTPA, 99mTc-DTPA, and inulin. The Modification of Diet in Renal Disease Study. AB - Assessment of glomerular filtration rate (GFR) with inulin is cumbersome and time consuming. Radioisotopic filtration markers have been studied as filtration markers because they can be used without continuous intravenous (IV) infusion and because analysis is relatively simple. Although the clearances of 99mTc diethylenetriamine-pentaacetic acid (DTPA), 169Yb-DTPA, and 125I-iothalamate have each been compared with inulin, rarely has the comparability of radioisotopic filtration markers been directly evaluated in the same subject. To this purpose, we determined the renal clearance of inulin administered by continuous infusion and the above radioisotopic filtration markers administered as bolus injections, simultaneously in four subjects with normal renal function and 16 subjects with renal insufficiency. Subjects were studied twice in order to assess within-study and between-study variability. Unlabeled iothalamate was infused during the second half of each study to assess its effect on clearances. We found that renal clearance of 125I-iothalamate and 169Yb-DTPA significantly exceeded clearance of inulin in patients with renal insufficiency, but only by several mL.min-1.1.73m 2. Overestimation of inulin clearance by radioisotopic filtration markers was found in all normal subjects. No differences between markers were found in the coefficient of variation of clearances either between periods on a given study day (within-day variability) or between the two study days (between-day variability). The true test variability between days did not correlate with within-test variability. We conclude that the renal clearance of 99mTc-DTPA, 169Yb-DTPA, or 125I-iothalamate administered as a single IV or subcutaneous injection can be used to accurately measure GFR in subjects with renal insufficiency; use of the single injection technique may overestimate GFR in normal subjects. PMID- 2205099 TI - Beta microseminoprotein is not a prostate-specific protein. Its identification in mucous glands and secretions. AB - Beta microseminoprotein (beta inhibin, PSP94), an unglycosylated protein of 94 amino acids with unknown function, is one of the predominating proteins in the secretion of the human prostate gland. In this work the authors have demonstrated that the expression of beta microseminoprotein is not restricted to the prostate and that the protein has a previously unrecognized widespread occurrence in the human body. According to radioimmunoassay, beta microseminoprotein immunoreactivity is present in many nonprostatic body fluids. The highest concentrations were found in secretions from the respiratory tract; in tracheobronchial fluid sometimes even at concentrations comparable to that in seminal plasma (about 1 g/l). Intermediate concentrations were found in gastric juice and some samples of secretion from the uterine cervix, whereas tears, saliva, pancreatic juice, bile, and mucus from the colon had low concentrations. According to gel chromatography, the molecular size of the beta microseminoprotein immunoreactivity present in tracheal fluid, gastric juice, and secretion from the uterine cervix did not differ from that of beta microseminoprotein in seminal plasma. The beta microseminoprotein immunoreactive component present in gastric juice had the same amino-terminal amino acid sequence as prostatic beta microseminoprotein (14 residues identified in material purified from gastric juice), providing further evidence for chemical identity of a nonprostatic beta microseminoprotein with the prostatic protein. Immunohistochemical staining with affinity-purified antibodies demonstrated the presence of beta microseminoprotein in many tissues, including the goblet cells in the tracheobronchial epithelium, tracheobronchial submucosal glands, certain mucosal cells in the antrum of the stomach, some glands of Brunner in the duodenum, and in parts of the mucosa of the colon. At least in the respiratory tract, the staining was localized to mucus-containing cells. beta microseminoprotein immunoreactivity also was localized to the cilia of the ciliated epithelium in the respiratory tract, the fallopian tubes, and the Gartner ducts of the uterine cervix. The pattern of tissue distribution of beta microseminoprotein found in this work indicates a connection of beta microseminoprotein with mucous secretions. PMID- 2205101 TI - Differential diagnosis of chronic facial, head, and neck pain conditions. PMID- 2205100 TI - C-myc proto-oncogene amplification detected by polymerase chain reaction in archival human ovarian carcinomas. AB - Polymerase chain reaction (PCR) technology was used to examine the state of amplification of the proto-oncogene c-myc in archival ovarian carcinomas. Sequences from the c-myc gene and from a control gene were amplified simultaneously by PCR and the ratios of the two products measured. The results provided an accurate measurement of the relative number of copies of the two genes in each tumor genome if the control and test sequences amplified by PCR were of equal lengths. The results were not affected by the number of PCR cycles used. This technique should facilitate gene amplification studies in clinical medicine. Increased c-myc copy number was found in 17% of the 30 cases examined when a control from the same chromosome as c-myc was used, but in 37% of cases if a control from another chromosome was used. This underlines the importance of the genetic location of the selected control genes for such studies. PMID- 2205102 TI - Cranial thickening in an Australian hominid as a possible palaeoepidemiological indicator. AB - This paper describes the cranial thickening of a late Pleistocene hominid (Willandra Lakes Hominid 50) from Australia. The unusual development of the vault structures in this individual has few, if any, equals among other hominids or more recent populations from around the world. The vault morphology is, therefore, described in terms of a pathologically related condition associated with the modern haemolytic blood dyscrasias, typical of sickle cell anamia and thalassemia. A possible palaeoepidemiology for these genetic adaptations among early Australasian populations is proposed together with a discussion of similar changes observed in the vault of the Singa calvarium from the Sudan. It is tentatively suggested that the cranial thickening of the Australian hominid has its origins in some form of genetic blood disease and that if this diagnosis is correct, this individual provides a rare glimpse of human biological adaptation in the late Upper Pleistocene. PMID- 2205103 TI - Patterns of enamel hypoplasia in two medieval populations from Nubia's Batn el Hajar. AB - Analysis of enamel hypoplasia frequencies for two medieval populations representing the earliest and latest Christian periods of ancient Nubia reveals important diachronic shifts in childhood stress. The mean frequency for hypoplastic bands among the early Christians is 4.2, while the late Christian sample has a mean frequency of 3.7. In addition, the earlier Christians show a prolongation of hypoplastic occurrences through childhood corresponding to a prolonged period of intensified childhood mortality. The modal time interval between hypoplastic occurrences is also shorter for the early Christian children. A comparison of hypoplasia frequencies by sex also reveals a pattern of considerable interest. Females show both lower frequencies of hypoplasias as well as a delay in onset. The diachronic differences are consistent with other indications from paleopathology and paleodemography that childhood stress decreased in later Christian times. The sex differences suggest that during the infancy and early childhood females were more resilient than their male counterparts. PMID- 2205104 TI - Continuing periosteal apposition. I: Documentation, hypotheses, and interpretation. AB - Continuing periosteal apposition (CPA) of small amounts of new lamellar bone, leading to absolutely larger size, has been identified in a number of adult cranial and postcranial bones. This paper reviews 42 studies published since 1964 that have found both significant and nonsignificant age-related change in various skeletal size dimensions, e.g., length, diameter, width, and area. Also considered are four hypotheses that have, or may be, postulated for the occurrence of CPA. To date, however, these hypotheses (cohort effect, mechanical compensation, bone repair and/or mechanical response potential, and heterochrony) have not been rigorously tested, hence remain speculative. An important interpretive problem that befalls the investigation of CPA is its small effect size (i.e., the magnitude of change between observations), since most studies have restricted sample sizes. This problem is illustrated by power analysis of three reviewed studies that reported nonsignificant age-related change. The analysis indicates that these studies had very little likelihood of finding a statistically significant result, i.e., a low probability of rejecting the null hypothesis stipulating no size change with age. This finding has implications for interpreting CPA and for distinguishing between the statistical and biological significance of this phenomenon. PMID- 2205105 TI - Development and biological applications of chloride-sensitive fluorescent indicators. AB - Chloride movement across cell plasma and internal membranes, is of central importance for regulation of cell volume and pH, vectorial salt movement in epithelia, and, probably, intracellular traffic. Quinolinium-based chloride sensitive fluorescent indicators provide a new approach to study chloride transport mechanisms and regulation that is complementary to 36Cl tracer methods, intracellular microelectrodes, and patch clamp. Indicator fluorescence is quenched by chloride by a collisional mechanism with Stern-Volmer constants of up to 220 M-1. Fluorescence is quenched selectively by chloride in physiological systems and responds to changes in chloride concentration in under 1 ms. The indicators are nontoxic and can be loaded into living cells for continuous measurement of intracellular chloride concentration by single-cell fluorescence microscopy. In this review, the structure-activity relationships for chloride sensitive fluorescent indicators are described. Methodology for measurement of chloride transport in isolated vesicle and liposome systems and in intact cells is evaluated critically by use of examples from epithelial cell physiology. Future directions for synthesis of tailored chloride-sensitive indicators and new applications of indicators for studies of transport regulation and intracellular ion gradients are proposed. PMID- 2205106 TI - Quantitative comparison of pathways of hepatic glycogen repletion in fed and fasted humans. AB - The effect of fasting vs. refeeding on hepatic glycogen repletion by the direct pathway, i.e., glucose----glucose 6-phosphate (G-6-P)----glycogen, was determined. Acetaminophen was administered during an infusion of glucose labeled with [1-13C]- and [6-14C]glucose into four healthy volunteers after an overnight fast and into the same subjects 4 h after breakfast. 13C enrichments in C-1 and C 6 of glucose formed from urinary acetaminophen glucuronide compared with enrichments in C-1 and C-6 of plasma glucose provided an estimate of glycogen formation by the direct pathway. The specific activity of glucose from the glucuronide compared with the specific activity of the plasma glucose, along with the percentages of 14C in C-1 and C-6 of the glucose from the glucuronide, also provided an estimate of the amount of glycogen formed by the direct pathway. The estimates were similar. Those from [6-14C]glucose would have been higher than from [1-13C]glucose if the pentose cycle contribution to overall glucose utilization had been significant. After an overnight fast, during the last hour of infusion, 49 +/- 3% of the glycogen formed was formed via the direct pathway. After breakfast, at similar plasma glucose and insulin concentrations, the percentage increased to 69 +/- 7% (P less than 0.02). Thus the contributions of the pathways to hepatic glycogen formation depend on the dietary state of the individual. For a dietary regimen in which individuals consume multiple meals per day containing at least a moderate amount of carbohydrates most glycogen synthesis occurs by the direct pathway. PMID- 2205107 TI - Kinetics and specificity of insulin uptake from plasma into cerebrospinal fluid. AB - To characterize the relationship between insulin levels in plasma and those in cerebrospinal fluid (CSF), we studied the kinetics of both the uptake of insulin into CSF from plasma and the turnover of insulin within the CSF compartment. Sustained physiological levels of euglycemic hyperinsulinemia (plasma insulin approximately 500 pM) did not alter CSF insulin levels within the 1st h, but by 90 min a significant increase was observed (P less than 0.01). During graded hyperinsulinemic clamps (mean plasma insulin approximately 500-15,000 pM), CSF insulin rose in a dose-dependent fashion. This rise was characterized by an initial delay followed by a continuous increase for the next 150 min. We also found that after brief, high-dose intravenous insulin infusions, the t1/2 of CSF insulin was 143 +/- 7 min (means +/- SE; n = 4), similar to that of CSF turnover by bulk flow. To test the specificity of CSF insulin uptake from plasma, we compared this uptake during intravenous insulin infusions with that of proinsulin, a peptide with reduced affinity for the insulin receptor. We observed a significantly lower increment of CSF proinsulin levels over 180 min (13.6 +/- 1.6 pM; means +/- SE; n = 4) compared with that of insulin (22.4 +/- 0.6 pM; n = 4; P less than 0.01), despite plasma proinsulin levels higher than insulin (1,890 +/- 287 vs. 1,283 +/- 192 pM; P less than 0.001). When corrected for the difference in plasma levels, the uptake of insulin was fivefold greater than that of proinsulin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2205108 TI - Measurement of lactate formation from glucose using [6-3H]- and [6-14C]glucose in humans. AB - To assess the validity of determining the origin of plasma lactate from the ratio of lactate and glucose specific activities (SA) during infusion of labeled glucose, normal subjects received infusions of [6-3H]- and [6-14C]glucose for 4 h after a 12 h fast, and, on another day, cold glucose labeled with both tracers during 4-6 h of hyperinsulinemia (approximately 650 microU/ml). Basally, less lactate was derived from plasma glucose when measured with [6-3H]glucose (27 +/- 2%) than with [6-14C]glucose (40 +/- 2%, P less than 0.001). Insulin did not increase the percent of lactate derived from plasma glucose when measured with [6 3H]glucose (29 +/- 2%) but did increase when measured with [6-14C]glucose (60 +/- 4%). The arterialized blood (A) [3H]lactate SA was 30-40% higher (P less than 0.01) than deep venous blood (V) [3H]lactate SA, whereas A and V [14C]lactate SA were similar. During conversion of alanine to lactate with glutamic-pyruvic transaminase (GPT) and lactate dehydrogenase (LDH) in vitro, 32 +/- 2% of 3H in [3-3H]alanine was found in water and 68 +/- 2% in lactate. During infusion of [6 3H]- and [6-14C]glucose, the ratio of [14C]alanine to lactate SA (0.88 +/- 0.05) was less than the ratio of [3H]alanine to lactate SA (0.31 +/- 0.03, P less than 0.001). In conclusion 1) loss of 3H relative to 14C from position 6 in glucose occurs during lactate formation in extrahepatic tissues possibly due to the GPT reaction (alanine conversion to pyruvate), and 2) even under supraphysiologic hyperinsulinemic conditions not all of plasma lactate originates from plasma glucose. PMID- 2205109 TI - Insulin stimulates mitochondrial protein synthesis and respiration in isolated perfused rat heart. AB - The rates of synthesis of mitochondrial proteins by both the cytoplasmic and mitochondrial protein synthetic systems, as well as parameters of respiration, were measured and compared in mitochondria isolated from fresh, control perfused, and insulin-perfused rat hearts. The respiratory control ratio (RCR) in mitochondria from fresh hearts was 8.1 +/- 0.4 and decreased to 6.0 +/- 0.2 (P less than 0.001 vs. fresh) in mitochondria from control perfused hearts and to 6.7 +/- 0.2 (P less than 0.005 vs. fresh and P less than 0.02 vs. control perfused) for mitochondria from hearts perfused in the presence of insulin. A positive correlation between the RCR and the rate of mitochondrial translation was demonstrated in mitochondria from fresh hearts. In mitochondria isolated from control perfused hearts, the rate of protein synthesis decreased to 84 +/- 3% of the fresh rate after 30 min of perfusion and fell further to 64 +/- 3% after 3 h of perfusion. The inclusion of insulin in the perfusion buffer stimulated mitochondrial protein synthesis 1.2-fold by 1 h (P less than 0.005) and 1.34-fold by 3 h of perfusion (P less than 0.001). The addition of insulin to 1-h control perfused hearts shifted the rate of mitochondrial protein synthesis from the control level to the insulin-perfused level within 30 min of additional perfusion, whereas 1 h was required to shift the RCR values of these mitochondria from control levels to insulin-perfused levels. Thus, whereas RCR was a useful predictor of mitochondrial translation rates, it did not account for the effects of insulin on mitochondrial translation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2205110 TI - Age-related differences in norepinephrine kinetics: effect of posture and sodium restricted diet. AB - We used compartmental analysis to study the influence of age on the kinetics of norepinephrine (NE) distribution and metabolism. Plasma NE and [3H]NE levels were measured in 10 young (age 19-33 yr) and 13 elderly (age 62-73 yr) subjects in the basal supine position, during upright posture, and after 1 wk of a sodium restricted diet. We found that the basal supine release rate of NE into the extravascular compartment, which is the site of endogenous NE release (NE2), was significantly increased in the elderly group (young, 9.6 +/- 0.5; elderly, 12.3 +/- 0.8 nmol.min-1.m-2; means +/- SE; P = 0.016), providing direct evidence for an age-related increase in sympathetic nervous system (SNS) tone. Although upright posture led to a greater increase in plasma NE in the young (0.90 +/- 0.07 to 2.36 +/- 0.16 nM) than in the elderly (1.31 +/- 0.11 to 2.56 +/- 0.31 nM; age group-posture interaction, P = 0.02), the increase in NE2 was similar between the young (9.6 +/- 0.6 to 16.2 +/- 1.5 nmol.min-1.m-2) and the elderly (11.6 +/- 1.4 to 16.1 +/- 2.4 nmol.min-1.m-2; posture effect, P = 0.001; age group-posture interaction, P = 0.15). Thus the increase in SNS tone resulting from upright posture was similar in young and elderly subjects. Plasma NE levels increased similarly in both groups after a sodium-restricted diet (diet effect, P = 0.001; age group-diet interaction, P = 0.23). However, NE2 did not increase significantly in either group (diet effect, P = 0.26), suggesting that SNS tone did not increase after a sodium-restricted diet. Compartmental analysis provides a description of age-related differences in NE kinetics, including an age-related increase in the extravascular NE release rate. PMID- 2205111 TI - Effects of naloxone on renin and pressor responses to acute renal hypotension in rats. AB - Reduction of renal perfusion is followed by increases in plasma renin activity (PRA) and arterial pressure. The present experiments were designed to determine if an opiate antagonist would alter pressor or renin responses to acute reduction of renal arterial pressure (RAP) in anesthetized rats. Male Sprague-Dawley rats were anesthetized with Inactin, and an adjustable constrictor device was placed around the abdominal aorta proximal to the renal arteries. One-half of the animals were pretreated with the opiate antagonist naloxone (2 mg/kg iv), and the other one-half were pretreated with saline vehicle. The abdominal aorta was then constricted to reduce RAP by 25% (measured as femoral arterial pressure) in one half of the animals in each pretreatment group. Compared with vehicle pretreatment, naloxone pretreatment did not alter the PRA response to aortic constriction; however, naloxone did attenuate the pressor response. We conclude that 1) the PRA response to acute reduction of renal arterial pressure is not dependent on an opiate mechanism in the rat, and 2) attenuation of the pressor response to aortic constriction by naloxone in intact rats is not secondary to a suppression of the PRA response. PMID- 2205113 TI - Turning points in twentieth-century American psychiatry. AB - The author examines four major turning points in twentieth-century American psychiatry, emphasizing the movement during the post-World War II period toward a psychotherapeutic/psychoanalytic approach and the emergence of biological psychiatry, neuroscience, and logical positivism during the 1970s and 1980s. He discusses the impact of Adolf Meyer during the mid-twentieth century and his ongoing influence. The final turning point involves a prediction of a late twentieth-century change, including new directions in nosology, emphasis on combined pharmacotherapeutic/psychotherapeutic treatments, efforts to create alternatives to full inpatient care, better outcome data for psychiatric treatments, and beginning resolution of major boundary problems of current practice. PMID- 2205112 TI - A comparison of absorption of glycerol tristearate and glycerol trioleate by rat small intestine. AB - Generally, fats rich in saturated fatty acids raise serum cholesterol, whereas fats rich in polyunsaturated fatty acids lower it. There appear to be exceptions; e.g., stearic acid (18:0)-rich fats have little or no effect on serum cholesterol concentrations. This apparent lack of cholesterolemic effect of stearic acid-rich fat could be because intestinal absorption of fat is poor or subsequent plasma and/or tissue metabolism of fat is different. To investigate mechanisms involved, we compared intestinal digestion, uptake, and lymphatic transport of glycerol tristearate (TS) and glycerol trioleate (TO, 18:1). Two groups of rats bearing intestinal lymph fistulas were used. TO rats were fed intraduodenally for 8 h at a constant rate a lipid emulsion of 25 mumols/h of TO (labeled with glycerol tri[9,10 (n)-3H]oleate), 7.8 mumols of egg phosphatidylcholine, and 57 mumols of sodium taurocholate in 3 ml of phosphate-buffered saline. TS rats were fed the same lipid emulsion except that TS replaced TO and the emulsion was labeled with glyceryl [1,3-14C]tristearate. The lymph triglyceride and radioactivity were determined. After infusion, the luminal and mucosal radioactive lipid content was analyzed. The results showed that there was significantly less lipid transported in the lymph of TS rats compared with TO rats. The results also showed a significant decrease in the absorption of TS as compared with TO. This was due in part to poor lipolysis. In addition, the lipid absorbed by the intestine of the TS rats was transported into lymph less efficiently than in TO rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2205114 TI - Evidence of the role of psychosocial factors in diabetes mellitus: a review. AB - Diabetes mellitus is a very prevalent illness that produces a variety of stresses for the individual patient, but the role of psychosocial factors in this illness is frequently minimized in the teaching of physicians and the care of patients. The authors review a framework for evaluating the role of psychosocial issues in illness in general and examine the evidence that demonstrates the importance of these issues in diabetes. PMID- 2205115 TI - Effects of doxepin on withdrawal symptoms in smoking cessation. AB - In a double-blind study, 15 cigarette smokers self-monitored 10 withdrawal symptoms. For the first 21 days (baseline), subjects received doxepin hydrochloride, up to 150 mg/day, or inert medication while continuing to smoke. On day 22, they were instructed to stop smoking; medication was continued. Withdrawal symptoms on the first 28 days of treatment (baseline and 7 days of attempted cessation) were analyzed. During cessation, subjects taking doxepin reported significantly less craving for cigarettes. Results from this study and others suggest that antidepressants may attenuate the severity of symptoms during withdrawal from addictive substances. PMID- 2205116 TI - Health status of migrant farmworkers: a literature review and commentary. AB - I made a computerized search of MEDLINE files from 1966 through October 1989 followed by a review of this literature. Four hundred eighty-five articles were scanned; 152 were found specifically related to migrant families, while another 51 articles addressed the health of agricultural workers or farmers in general. Solid data exist on dental health, nutrition and, to a lesser extent, childhood health. Data also were prominent in several disease categories including certain infectious diseases, pesticide exposures, occupational dermatoses, and lead levels in children. Estimates of the size of the migrant and seasonal farmworker population vary widely. Basic health status indicators such as age-related death rates are unknown. Prevalence rates of the most common cause of death in the United States have yet to be studied. More research is needed into the health problems and health status of migrant and seasonal farmworker families. PMID- 2205118 TI - [Hysterographic follow-up of the results of treating uterine synechiae with an intrauterine contraceptive pessary]. AB - The authors discuss the results from roentgenological (cervical hysterography) examination of the uterine cavity, aiming to confirm the results from the treatment of intrauterine synechiae. It was established that there were no roentgenological data for synechiae after the conducted treatment in 73.9% of the examined hysterograms. The treatment had no substantial effect only in 8.7% of women as synechiae remained unchanged. Very good results were obtained after usage of the intrauterine contraceptive devices--Super Dana and Lippes, possessing volumetric and stretching form in respect to the uterine cavity. The authors conclude that the hysterography is exact diagnostic method for confirming the effect of treatment of synechiae in the uterine cavity with suitable intrauterine loops. PMID- 2205117 TI - [The relationship of the location of the placenta and the indices of the fetus and birth process]. AB - The study is carried out on 200 women, pregnant for first and second time with normally progressing, pregnancy and delivered by normal mechanism at term, who are divided into groups according to the localization of the placenta, established by ultrasound examination. The number of primiparas is 50% in each group. The authors find that when the placenta is located on the uterine fundus larger children are born and hypokinetic labour activity is observed as well as protracted delivery. The site of the placenta is extremely important factor, affecting course of pregnancy and delivery. PMID- 2205119 TI - [Hydatidiform mole--current knowledge]. PMID- 2205120 TI - The Dandy-Walker syndrome. Relevance to anaesthesia and intensive care. PMID- 2205122 TI - High frequency weaning. PMID- 2205121 TI - Ginger root--a new antiemetic. The effect of ginger root on postoperative nausea and vomiting after major gynaecological surgery. AB - The effectiveness of ginger (Zingiber officinale) as an antiemetic agent was compared with placebo and metoclopramide in 60 women who had major gynaecological surgery in a double-blind, randomised study. There were statistically significantly fewer recorded incidences of nausea in the group that received ginger root compared with placebo (p less than 0.05). The number of incidences of nausea in the groups that received either ginger root or metoclopramide were similar. The administration of antiemetic after operation was significantly greater in the placebo group compared to the other two groups (p less than 0.05). PMID- 2205123 TI - Hybrid biosensor for the determination of lactose. AB - Genetically manipulated bacteria Escherichia coli K-12 recombinant PQ-37 and glucose oxidase (EC 1.1.3.4) were used for the construction of a hybrid lactose sensor because of the hyperproduction of beta-galactosidase (EC 3.2.1.23) by E. coli effected by a genotoxic agent. The biocatalytic layer was prepared by coimmobilization of the E. coli cells with glucose oxidase on the nylon network via glutardialdehyde and fixed to the Clark oxygen electrode. The influence of pH, temperature, and concentration of activators of beta-galactosidase on the sensor response was tested. Analyses of milk products were completed without any special pretreatment of the samples. The contents of lactose determined by hybrid sensor agree with conventional photometric measurements. Standard relative deviation is less than 3% for all samples. The half-life of operational stability is 30 days. PMID- 2205124 TI - NMR spectroscopy and cancer research: the present and the future. PMID- 2205125 TI - ["Utterances of pure experience." The reflection of Hippocratic thought in Goethe's poetry]. AB - Many important treatises attributed to the founder of medical science and now united in the HIPPOCRATIC CORPUS, the body of Hippocrates' books, interested Goethe throughout his life, influenced his view of the world and stimulated his poetic work. Johann Georg Zimmermann's (1728-1795) perception of Hippocrates had a particularly profound effect and induced Goethe to consider Hippocrates' heritage from the "experience" aspect as a model of how man should consider the world and . . . record its events for posterity'. He studied Hippocrates' Airs, Waters and Places, which deals with environmental factors, and the treatise On Regimen especially thoroughly. Goethe's study of the experience expressed in Hippocrates' Aphorisms was particularly fruitful for his "Wilhelm Meister". His reflections on the link between theory and practice, particularly in relation to the natural sciences, are also considered. PMID- 2205126 TI - [The historical problem of skull morphology--several scientific theoretical aspects]. AB - The morphology of the skull is considered in a historical and gnosological context. The development of corresponding knowledge and methods is characterized by several paradigmatic changes from the classical vertebral theory to consideration of the skull as a biotic system. The accumulation of empirical knowledge was accompanied by increasing divergence between studies concerning the suborganistic structural plane and approaches to the description of the skull in its entirety as a functional system. The latter calls for a methodologically ambitious synthesis of results obtained from studies concerning the embryology, phylogenesis and biomechanics of the vertebrate skull. PMID- 2205127 TI - Segmental motor and sensory innervation of muscles in anterior leg compartment as revealed by retrograde transport of horseradish peroxidase. AB - Horseradish peroxidase (HRP) tracing technique was used to label and localize motor and sensory neurons innervating tibialis anterior, extensor hallucis longus and extensor digitorum longus muscles of the anterior leg compartment of the rat. The tibialis anterior sensory neurons were located in the ipsilateral L4 and L5 spinal ganglia. Cells of origin of tibialis anterior motor endings were also found in the ipsilateral ventral horn of the same cord segments as the labeled sensory ganglia. Extensor hallucis longus sensory neurons were located in L4 to L6 spinal ganglia, while its labeled motor neurons were located in L4 and L5 spinal cord segments. The motor neurons innervating the extensor digitorum longus muscle were located in L4 to L6 spinal cord segments; its sensory neurons were previously localized. All labeled motor and sensory neurons were present on the ipsilateral side. Almost all motoneurons innervating the 3 muscles were present in the dorsolateral nucleus of the ventral horn. PMID- 2205129 TI - Effects of duration of fasting on gastric fluid pH and volume in healthy children. AB - To determine the effects of duration of fasting before elective surgery on gastric fluid pH and volume in children, a prospective, randomized, blinded study of 100 unpremedicated children, aged 1-14 yr, was undertaken. Each child was given 2 mL/kg of water orally and then fasted 2, 4, or 6 h preoperatively. After induction of anesthesia and tracheal intubation, gastric fluid was aspirated through a large-bore, multiorifice orogastric tube. Gastric fluid pH was measured using a calibrated PHM62 radiometer. Gastric fluid volume was the total volume of fluid aspirated from the stomach. The duration of fasting was between 2.0 and 8.5 h. We found that neither gastric fluid pH nor gastric fluid volume correlated with the duration of fasting. The mean (+/- SD) gastric fluid pH was 1.80 +/- 0.79 and the mean (+/- SD) gastric fluid volume was 0.56 +/- 0.39 mL/kg. Gastric fluid pH was less than 2.5 and volume greater than 0.4 mL/kg in 53% of children. We conclude that healthy children may receive 2 mL/kg of water up to 2 h before elective surgery without decreasing gastric fluid pH or increasing gastric fluid volume beyond values obtained after fasting for 6 h. PMID- 2205128 TI - Prophylactic oral naltrexone with intrathecal morphine for cesarean section: effects on adverse reactions and analgesia. AB - The influence of two different doses of oral naltrexone on the adverse effects and the analgesia associated with intrathecal morphine was compared in a double blind, placebo-controlled study. Thirty-five patients undergoing cesarean section were provided postoperative analgesia by 0.25 mg intrathecal morphine. Sixty minutes later they were given 6 mg naltrexone, 3 mg naltrexone, or placebo as an oral solution. Pain relief was assessed by the Visual Analog Scale. Requirements for additional analgesics and side effects were recorded. Duration of analgesia was shorter in the 3- and 6-mg naltrexone groups than in the placebo group, 10.0 +/- 2.6, 12.4 +/- 2.6, and 19.2 +/- 4.5 h (mean +/- SEM), respectively, but values did not reach statistical significance. The incidence of pruritus and vomiting was significantly less in the 6-mg naltrexone group than in the other two groups (P less than 0.05). Somnolence was significantly less in the 3- and 6 mg naltrexone groups than in the placebo group (P less than 0.05). Naltrexone (6 mg) is an effective oral prophylactic against the pruritus and vomiting associated with intrathecal morphine for analgesia after cesarean section, but it is associated with shorter duration of analgesia. PMID- 2205130 TI - Effect of cardiopulmonary bypass on plasma levels of nifedipine. AB - Blood levels of many medications are acutely lowered by cardiopulmonary bypass (CPB). Because nifedipine is often used to provide protection from coronary ischemia, a determination of the effect of CPB on plasma nifedipine levels might help to determine the potential clinical benefit of nifedipine during and after bypass. Four samples of blood were drawn from each of eight patients undergoing cardiac surgery: one before, two during, and one after CPB. Although plasma levels of nifedipine declined during and after bypass (P less than 0.05, analysis of variance), the time-course and slope of the decline indicate that this was an effect of normal metabolism of the drug rather than an effect of physiologic changes occurring during CPB. An important additional finding was that the majority of patients had subtherapeutic levels of nifedipine before bypass, suggesting that additional nifedipine given during and after surgery might be of benefit. The effect of the CPB circuit itself was also examined in vitro by mixing nifedipine into a pump prime solution that was then recirculated with 2 U of outdated blood while levels of nifedipine were measured for 3 h. Plasma levels did not change in either a CPB circuit exposed to light or kept in a darkened room. PMID- 2205131 TI - Local anesthetic serum concentrations after penile nerve block in children. PMID- 2205132 TI - A median epidural septum is not a common cause of unilateral epidural blockade. PMID- 2205134 TI - [Synthetic analgesic moradol at various stages of surgical treatment of patients with cancer]. AB - Moradol ("Galenika", Yugoslavia)/butorphanol tartrate ("Bristol--Mayers C.", USA)/, a synthetic analgesic representing a new generation of opiate receptors agonists-antagonists, devoid of any narcogenic potential has been used as the only analgesic at all stages of anesthesia during cancer surgery in 26 patients. For premedication moradol was used in a mean dose of 0.032 +/- 0.003 mg.kg-1 in combination with diazepam (0.153 +/- 0.005 mg.kg-1) and atropine (0.01 mg X X kg 1). For induction to anesthesia moradol was used in a dose of 0.72 +/- 0.003 mg.kg-1 and diazepam in a dose of 0.27 +/- 0.015 mg.kg-1. General anesthesia was maintained with moradol, diazepam, nitrous oxide and droperidol. The data presented in the paper demonstrate the advantages of moradol at all stages of intra- and postoperative analgesia, which ensures stable anesthetic background (according to hemodynamic parameters) and reduces considerably an overall postoperative analgesic dose. PMID- 2205133 TI - [The role of non-traditional methods of analgesia in the postoperative period]. AB - 192 patients, aged 33 to 67 years, predominantly after abdominal and small pelvic surgery have been examined. Non-conventional techniques of analgesia were used in most of patients: central electroanalgesia, transcutaneous peripheral and paravertebral electroanalgesia, corporal and auricular acupuncture. To ensure postoperative pain relief various types of electrical stimulation were applied using home-made devices, The efficacy of non-conventional anesthesia techniques in the postoperative period has been confirmed. PMID- 2205135 TI - [Premedication with intranasal midazolam in pediatric anesthesia]. AB - To evaluate nasally administered midazolam 0.2 mg.kg-1 for preinduction of anaesthesia in paediatric patients the authors studied ASA 1 patients scheduled for elective surgery. Forty-five children, ages 3 to 126 months, were randomized in three groups: group D (n = 16) received diazepam 0.33 mg.kg-1 orally, group P (placebo) (n = 13) 0.04 ml.kg-1 normal saline via the nasal route; in group MDZ (n = 16) the children were given intranasal midazolam 0.3 mg.kg-1. The premedication was assessed on a 5-point sedation scale, modified to include the response to mask placement and the quality of the induction of general anaesthesia. The degree of sedation, heart rate, blood pressure, respiratory rate and oxygen saturation levels were recorded on the arrival in the operating room (0 min) and 3, 6, 9, 12 and 15 min (mask placement) after drug administration. With intranasal midazolam sedation was demonstrable at 6 min and was significant at 9 and 12 min. In this group all the children were calm or drowsy. The induction of anaesthesia was equivalent in group D and MDZ but easier than in those patients receiving normal saline. Vital signs did not change during the study period in any of the three groups. Intranasal midazolam was slightly more effective than oral diazepam. In children, it produces anxiolysis and sedation with rapid onset and is an attractive alternative to other routes for preanaesthetic medication. PMID- 2205136 TI - [Epidemiologic study of risk factors associated with the development of respiratory pathology in children]. AB - A total of 1,566 children the area of Valencia (Spain), of both sexes and aged 7 to 14 received an epidemiological questionnaire recommended by the American Thoracic Society. Antecedents of asthma were recorded in 79 cases (5%), with a predominance among males; 73.3% of these children presented their first crisis before age three. Eighty-seven children were habitual smokers (5.6%), again with a predominance among males-most of these children being between 13 and 14 years old. A family history of smoking was observed in 82.8% of the children who were habitual smokers. A greater predominance of smoking mothers was observed at higher socio-economical levels--with no significant differences between parents. The incidence of respiratory pathology (cough and antecedents of bronchitis) was higher among children whose mothers (or both parents) were smokers. On comparing the two areas of the city with the greatest difference in air pollution level, no significant differences were observed in respiratory morbidity among the child population. PMID- 2205137 TI - [Repercussion of risk factors associated with the development of chronic bronchial pathology on pulmonary function in children]. AB - Of a total of 1,566 children, 1,416 of both sexes and aged 7 to 14 were subjected to functional respiratory exploration with a Vitalograph dry spirometer. The impact of tobacco smoke--as active and/or passive smokers--on the spirometric variables (FVC, FEV1, FEF2572, FEF50) evaluated by variance analysis (ANOVA) revealed no significant reductions. Asthma was the single antecedent of respiratory morbidity showing significant reductions in FEF2575, FEF50 among males alone; no significant reductions were observed for any of the other spirometric variables. No significant decreases were found in the spirometric variables on comparing two areas of the same city with the greatest difference in air pollution level. PMID- 2205138 TI - [Increased survival rates of children with cystic fibrosis]. AB - Seventy-two patients with cystic fibrosis were under care between January 1st 1972 and December 31st 1988, and 75 until now (July 1989). Fifty are alive, 24 died and 1 was lost to follow-up. The number of alive patients under control at the end of every year rose from 5 in 1972 up to 47 in 1988 and 50 at present. In order to assess the progress of survival rates, we compared two periods: 1972 1980 and 1981-1988. Twenty-eight were under control during the first period and 16 (57%) died, these figures for the second period being 55 and 8 (14%) (p 0.001) respectively. A remarkable increase in cumulative survival rates during the second period was observed at ages 1 (96% vs 68%), 5 (94% vs 55%) and 10 (86% vs 28%). Greater experience and closer follow-up, together with more aggressive treatment are likely to account for the increase in survival. It is vital that reference cystic fibrosis centers should be set-up in our country for the management of so complex a disease as 'cystic fibrosis. PMID- 2205139 TI - [Laryngitis epidemic (893 cases of acute laryngotracheitis and spastic croup). II. Clinical, diagnostic and therapeutic aspects]. AB - We retrospectively review 893 cases of children, occurred in epidemic bout in September-October 1987, in order to study the usual management of his pathology in our hospital. In most cases (82.3%) diagnose was laryngitis or acute laryngitis without specification acute laryngotracheitis or spasmodic group. Epiglottitis was no detected in any case. Complementary tests were performed only in 5% of the patients, but they were of little help for the diagnose. Treatment applied was ambiental hummidiffication (95.5%), followed by water and alcohol impregned neck collar (87.2%), rectal magnesium-sulfate + papaverine (67.5%), epinephrine nebulization (63%), antibiotics (44.3%), steroids (9%), bronchodilatadors (4.8%). This therapeutic approach is discussed. PMID- 2205140 TI - [Fetal cholelithiasis. A clinical case and review of the literature]. PMID- 2205141 TI - Foot problems in homeless persons. PMID- 2205142 TI - The soluble interleukin-2 receptor: biology, function, and clinical application. AB - PURPOSE: To review the biologic origin, functional characteristics, and current and potential clinical applications of a novel marker of immune system activation, the soluble interleukin-2 receptor (sIL-2R). DATA IDENTIFICATION: Studies reported since 1985 were identified by a computer search using MEDLINE as well as from bibliographies of published work. STUDY SELECTION: Sixty-two reports on the clinical applications of the sIL-2R, largely from peer-reviewed journals, were identified. These reports address the utility and significance of sIL-2R measurements in various conditions. Basic scientific investigations delineating the biochemical and molecular features of the human interleukin-2 receptor complex and the sIL-2R protein were reviewed. DATA EXTRACTION: The validity of sIL-2R quantitation as an index of in-vivo immune system activation and its usefulness as a measure of disease activity and outcome were examined. RESULTS OF DATA ANALYSIS: The quantitation of sIL-2R, a novel laboratory measure of in-vivo immune system activation, correlates reliably with disease activity in autoimmune inflammatory disorders, transplantation rejection, and specific infectious disorders. Markedly elevated serum sIL-2R levels are a particularly prominent feature of certain hematologic malignancies, such as human T lymphotropic retrovirus type I-associated adult T-cell leukemia and hairy cell leukemia, reflecting tumor burden and response to therapy. The sIL-2R level at disease onset may also reliably predict long-term prognosis in non-Hodgkin lymphoma, and it appears to provide an additional serologic measure in the assessment of clinical progression in patients with human immunodeficiency virus infection and the acquired immunodeficiency syndrome. CONCLUSIONS: Studies have suggested that sIL-2R levels offer a rapid, reliable, and noninvasive measure of disease activity, response to therapy, and, in some cases, prognosis in a broad spectrum of conditions associated with T- or B-cell immune activation. PMID- 2205143 TI - Cost of VA medical care. PMID- 2205144 TI - A review of exposure conditions and possible health effects associated with aerosol and vapour from low-aromatic oil-based drilling fluids. AB - This paper reviews investigations on possible health effects after inhalation of aerosol and vapour from the low-aromatic oil-based drilling fluids which have replaced the diesel-based fluids. The main advantage of the low-aromatic base oils with respect to health hazard is their lower volatility. However, some aliphatic and naphthenic hydrocarbons are distributed more efficiently to the brain than are the corresponding aromatic ones. Reducing the content of aromatic hydrocarbons becomes particularly important when the upper end of the boiling point range is sufficiently high for the base oil to contain carcinogenic polycyclic aromatic hydrocarbons (PAH). As a result of enclosure and local extract ventilation it has been possible to reduce time-weighted average concentrations of aerosol and vapour to below 100 mg m-3. Effects on the central nervous system have only been observed at higher concentrations of the actual hydrocarbons, and male rat hydrocarbon nephropathy is not considered predictive of a normal human response. Insufficient information is available on possible long-term effects of exposure to the low-aromatic oil-based drilling fluids, especially regarding carcinogenicity and changes in the lungs. PMID- 2205145 TI - [Post-varicella anetoderma. 3 cases]. AB - We report three cases of typical macular atrophy which appeared during, or was noticed shortly after varicella. The three patients were children. These cases were particular in that anetoderma lesions occurred independently of the scarring varicella lesions and followed a prolonged course of their own afterwards. We were unable to classify these cases in the primary or secondary type of macular atrophy. The various dermatoses associated with macular atrophy and the numerous physiopathological hypotheses put forward concerning this entity are enumerated. PMID- 2205146 TI - [Leukocytoclastic vasculitis. New physiopathologic concepts]. PMID- 2205147 TI - [Detection of respiratory allergies using the Phadiatop test in children 1 to 6 years of age]. AB - Phadiatop, a new test for detecting hypersensitivity to airborne allergens, was used in 83 children aged 9 months to 6 years with recurrent respiratory manifestations, i.e. recurrent expiratory obstruction and/or recurrent respiratory infections. A good correlation was found between this test and both the prick tests (95%) and the specific IgE assays (91% for RASTS of classes greater than or equal to 1, and 95% for RASTS of classes greater than or equal to 2). However, the correlation was less strong with the total IgE level (68%). The overall correlation with the specialist's prediction based on history and physical evaluation was excellent (94%). In this study, Phadiatop was found to have a 90% sensitivity and a 98% specificity. Furthermore, this test costs 40% less than the often used strategy combining skin tests and determinations of total and specific IgE levels. In the age group studied, Phadiatop is most useful above the age of two, since in younger patients true respiratory allergies are fairly infrequent in recurrent ENT and lower respiratory tract infections, whereas infections are far more common. PMID- 2205149 TI - [Mesenteric cystic lymphangioma in children. Report of a case manifested by anemia]. AB - A case of mesenteric cystic lymphangioma revealed by hypochromic anemia and abdominal pain, secondary to an intracystic hemorrhage is reported in a 4-year old child. Etiology, pathology, diagnosis, treatment and prognosis of mesenteric lymphangioma in children are reviewed. PMID- 2205148 TI - [Urethral stricture in children. Long term results of surgical treatments]. AB - Thirty-six urethral strictures were treated between 1977 and 1984. Three strictures were considered to be congenital, eleven were traumatic and twenty-two were iatrogenic. The authors performed twenty five internal urethrotomies, twelve resection-sutures of the urethra and eleven urethroplasties including eight patch grafts with a pedicle derived from scrotal or penile skin, a tubed pedicle scrotal skin flap, one Jurascek urethroplasty and one Leveuf urethroplasty. Internal urethrotomy only gave 50% of good results and is now reserved for short strictures less than one centimetre in length. Resection-suture is an excellent operation which should be reserved for strictures less than two centimetres in length: it gave 84% of good results. One of the various types of pedicle cutaneous urethroplasty is certainly the best operation for long strictures: it gave more than 90% of good results in the present series. PMID- 2205150 TI - [Aortic insufficiency and degenerative aortic disease. Anatomic study and etiology]. AB - Degenerative (or dystrophic) artery disease is the most recently recognized etiology of aortic regurgitation (AR) and has been observed since the sixties. This condition concerns about one third of the pure AR cases, which now undergo surgery and involves two populations (with a marked predominance of men): subjects over 50 years of age, with no special history, and some post-adolescent patients suffering from Marfan's disease. The anatomical lesions are identical in three respects: the ascending aorta, with a spindle-like aneurysm, thin or slack, collapsed aortic sigmoids, dilated aortic ring. The histopathologic observations involve two features, the relative importance of which varies from one case to another: a loss of elastin and collagen fibers (the main cause of the disease) and an accumulation of acidic mucopolysaccharides (known as mucoid or myxoid degeneration) which involves some reaction to hemodynamic turbulence and is somewhat secondary to fragilization of the aorta or sigmoid wall. Rupture of the aorta wall, which is restricted to the inner two thirds of the media or complicated by a dissecting hematoma, may aggravate both the distention of the ascending aorta and the AR. One hundred of the 150 cases of pure AR which underwent surgery at Lyon (France) during 1986 and 1987 belonged to this dystrophic etiologic category and called for a special procedure (Bentall). PMID- 2205151 TI - [Coronary insufficiency caused by atherosclerosis. Current pathogenic concepts, clinical, angio-anatomic correlations and therapeutic deductions]. AB - The multiplicity of clinical expressions of coronary artery failure results from the interaction between three processes which varies from one patient to another and from one time to another in a given patient. The three processes involved are: atheromatous coronary stenosis, arterial spasm and the development of a fibrino-thrombocytic thrombus. In stable angina pectoris, atheromatous narrowing, with smooth, regular outlines, no endothelial injury and little likelihood of complication by thrombosis predominates. In contrast, labile angina and myocardial infarction give rise to the same lesions: usually irregular stenoses, with a narrow neck and irregular outline. They correspond histologically to the rupture of an atheroma plaque, frequently complicated by the appearance in situ of a clot. In the authors' experience, complete arterial occlusion ensues in three out of four cases. The rate at which aggravation progresses and the variable degree of collateral circulation explains why a whole range of intermediate clinical expressions are possible, ranging from labile angina to sudden death of ischemic origin, and including various forms of infarction (both with and without the Q wave). Healing of these lesions may also be observed, usually resulting in progression of the coronary stenosis and sometimes of modification of left ventricular function of variable duration (myocardial stunning or hibernation). The importance of thrombotic phenomena in triggering the most serious forms of coronary artery failure (labile angina and myocardial infarction) provides a more precise identification of the place of thrombolytic treatment. In addition, it appears that there is no point in emergency revascularization of the ischemic myocardium. However, despite recent clinical progress, coronary artery disease remains a worrying illness which calls for primary prevention measures. Such measures must be undertaken as soon as possible if they are to be effective. PMID- 2205152 TI - [Iatrogenic arteriovenous fistula between the internal mammary artery and the innominate venous trunk. Contribution of digital arteriography in the positive and anatomic diagnosis]. AB - The authors report the case of an arterio-venous fistula between the internal mammary artery and the trunk of the innominate vein following puncture of the internal jugular. The clinical signs of this unusual complication led the authors to list the differential diagnoses which should be considered and to draw attention to the importance of digitalized angiography in anatomical diagnosis. PMID- 2205153 TI - [A rare complication of thoracic radiotherapy: auriculoventricular block. Apropos of a case and review of the literature]. AB - The authors report the case of a 30-year old patient who presented atrioventricular block 12 years after mediastinal radiation treatment of Hodgkin's disease. This patient had been monitored in the service for 3 years after the insertion of a pacemaker. A review of the literature, identified 15 cases of post-radiation AV block. The AV block was subnodal in the 7 cases which were subjected to endocavitary recording. PMID- 2205154 TI - [Diagnosis of pulmonary embolism. Paris, 26 January 1990]. PMID- 2205155 TI - [Coronary angioplasty in myocardial infarction: present status]. PMID- 2205156 TI - Analysis of a power theory for health promotion activities. PMID- 2205157 TI - Rubella reinfection. PMID- 2205158 TI - Diagnosis of neonatal chlamydial conjunctivitis. AB - Fifty seven babies with ophthalmia neonatorum had conjunctival smears examined by microscopy and bacterial culture, and by immunofluorescence, to find out which was the best method of diagnosing chlamydial conjunctivitis. The positive (33%) and negative (70%) predictive values of microscopy and culture were too low for us to accept it as an adequate method of detecting the presence of Chlamydia trachomatis. PMID- 2205159 TI - Aerosol therapy in the newborn. PMID- 2205160 TI - Revised criteria for diagnosis of coeliac disease. Report of Working Group of European Society of Paediatric Gastroenterology and Nutrition. PMID- 2205161 TI - Complement activation with bubble and membrane oxygenators in aortocoronary bypass grafting. AB - Thirty-three patients admitted for coronary bypass grafting were randomized to cardiopulmonary bypass with a bubble oxygenator (Cobe or Polystan) or a membrane oxygenator (SciMed). Plasma concentrations of C3 activation products and the terminal complement complex were measured using enzyme immunoassays. Both variables increased almost linearly after onset of cardiopulmonary bypass, with maximal concentrations at closure of the sternum. From a baseline of 7.5 to 12.0 arbitrary units (AU)/mL (medians), the concentrations of C3 activation products increased by 117.5 AU/mL (Cobe), 120.5 AU/mL (Polystan), and 213.3 AU/mL (SciMed). The increase in the membrane group was significantly higher than in the two bubble oxygenator groups (p less than 0.01). From a baseline of 0.9 to 1.3 AU/mL, the concentrations of terminal complement complex increased by 5.4 AU/mL (Cobe), 6.6 AU/mL (Polystan), and 7.7 AU/mL (SciMed) (differences not significant). The higher C3 activation caused by the membrane oxygenator may be explained by differences in flow profile and surface area in contact with blood. The study cannot confirm the general assumption that membrane oxygenators lead to lower complement activation than do bubble oxygenators. PMID- 2205162 TI - Pericardial window: mechanisms of efficacy. AB - Although the term implies a persistent communication through which fluid might drain, how a pericardial window works is not clear. We believe that the mechanism of success is not window but rather fusion of the epicardium to the pericardium with obliteration of the potential space. To evaluate this, we studied 28 patients, all of whom underwent a subxiphoid pericardial window procedure with tube drainage maintained until output was minimal. There were no operative deaths, and 26 patients (92.9%) obtained permanent relief. Postoperative echocardiograms demonstrated thickening of the pericardium/epicardium and obliteration of the pericardial space. Autopsy performed on 4 patients who died of their underlying malignancy confirmed this fusion, which begins as an inflammatory process. A subxiphoid pericardial window relieves effusions with a low operative mortality and good long-term success (92.9%, 26 of 28). This success is dependent on the inflammatory fusion of the epicardium to pericardium and not maintenance of a window. Tube decompression should be maintained until fluid output is minimal to allow apposition and fusion of the two surfaces. PMID- 2205163 TI - Systemic venous aneurysms. AB - A case of superior vena cava aneurysm combined with aneurysm of the left innominate vein is presented. For the diagnosis, it is important not only to apply imaging techniques such as superior vena caval angiography, radioisotopic angiography, and computed tomographic scans but also to have a concept of this entity in mind. PMID- 2205164 TI - A practical mechanical respirator, 1929: the "iron lung". AB - No satisfactory mechanical respirator existed before 1929, when Philip Drinker and Louis Shaw described an apparatus of their own design. This machine was in the form of a cylindrical tank enclosing the patient's body and chest, leaving the head outside the chamber under atmospheric pressure. Air pumps, later a bellows, raised and lowered pressure within the tank to assume the entire work of breathing. Popularly named the iron lung, the Drinker respirator supported thousands of patients afflicted with respiratory paralysis during the polio era. It was being superseded by positive-pressure airway ventilators just as the polio era came to a close. Today the Drinker respirator has disappeared virtually without a trace. Although its disadvantage was its cumbersome size, we must concede that it supported patients over the long term with fewer complications than do the respirators of today. PMID- 2205165 TI - Intrathoracic tumors of the vagus nerve. AB - Two patients had resection of a middle mediastinal neurilemmoma of the vagus nerve. Twenty-seven other neurogenic tumors of the intrathoracic vagus are reviewed. These tumors are generally asymptomatic except for hoarseness in an occasional patient. PMID- 2205167 TI - [Natural C-glycoside antibiotics and the approaches to determining the structure of their carbohydrate moiety]. PMID- 2205166 TI - Tuberculosis. PMID- 2205168 TI - [Aminoglycoside-inactivating enzymes: current status of the problem]. PMID- 2205170 TI - Legal, social, and biological definitions of pedophilia. AB - Although there is substantial evidence in the historical and anthropological record of the sexual use of children by adults, surprisingly little is known about the etiology of pedophilia or its relation to other forms of sexual aggression. After briefly reviewing the research on pedophilia, we argue that one major difficulty in conducting or interpreting such research lies in the different definitions "pedophilia" has received. Most important, much of the research has accepted a legal definition of pedophilia, treating all offenders convicted of "child molestation" as pedophiles, regardless of the age or appearance of the victim. We argue that a distinction should be made between biological children and sociolegal children. Laws governing child molestation reflect sociolegal childhood, regardless of its discrepancy with biological childhood. "True" pedophiles should be identified by their preference for biological children. By using legal classifications, researchers may well be confusing two distinct types of offenders, child molesters and rapists, and confounding attempts to understand pedophilia. PMID- 2205169 TI - Rape trauma syndrome as scientific expert testimony. AB - Behavioral science studies conducted on rape victims reveal a posttraumatic stress disorder which follows the attack known as rape trauma syndrome. Evidence of rape trauma syndrome can be very useful in explaining the behavior of rape victims. Rape trauma syndrome can help corroborate the victim's assertion of lack of consent and also help the jury understand the typical reactions of rape victims. Courts have held that expert testimony of rape trauma syndrome is admissible as evidence of (i) lack of consent, (ii) the amount of damages in civil suits, (iii) a defense to culpable behavior, and (iv) an explanation for behavior of the victim that is inconsistent with the claim of rape. Rape trauma syndrome meets the requirements for admissibility when it is used for the proper purpose and with adequate safeguards to prevent any unfair prejudice. Based on case precedent on the admissibility of rape trauma syndrome as scientific expert testimony, rape trauma syndrome should be admissible if (i) the evidence presented only shows the typical reactions to rape and does not make any legal conclusions as to whether the victim was raped, (ii) the expert is qualified, (iii) a proper foundation is laid, (iv) liberal cross-examination of the expert is allowed, and (v) the defense can introduce its own expert testimony on rape trauma syndrome. PMID- 2205171 TI - Sexual attitudes in the Chinese. AB - The sexual attitudes in the Chinese have been described by scholars as suppressive or nonsuppressive, based on observations made on various aspects of the Chinese culture. Many characteristics of the Chinese history and society are responsible for this controversy and confusion. The overall picture may be better understood using the developmental model propounded by some modern sociologists in the study of social units and collective behaviors. It is time to proceed from static to dynamic to try to apply this model in comprehending the sexual attitude of the Chinese and those of other cultures. PMID- 2205172 TI - Incidence and prevalence of the sexual dysfunctions: a critical review of the empirical literature. AB - The research which has assessed the incidence and prevalence of sexual dysfunctions is reviewed. Twenty-three studies are evaluated. Studies completed with community samples indicate a current prevalence of 5-10% for inhibited female orgasm, 4-9% for male erectile disorder, 4-10% for inhibited male orgasm, and 36-38% for premature ejaculation. Stable community estimates with regard to the current prevalence of female sexual arousal disorder, vaginismus, and dyspareunia are not available. Recent studies completed with clinical samples suggest an increase in the frequency of orgasmic and erectile dysfunction and a decrease in premature ejaculation as presenting problems. Desire disorders have increased as presenting problems in sex clinics, with recent data indicating that males outnumber females. Methodological limitations of these studies are identified and suggestions for future research are offered. PMID- 2205173 TI - Duplex imaging and incidence of carotid radiation injury after high-dose radiotherapy for tumors of the head and neck. AB - Radiation-induced carotid artery disease following high-dose (greater than 50-Gy) radiotherapy for head and neck cancer may become more common as improved treatment results in longer survival. Duplex ultrasound scans were obtained in 91 consecutive patients to determine whether increased incidence and severity of extracranial carotid disease correlate with prior radiotherapy. Fifty-three patients who underwent radiotherapy an average of 28 months previously and 38 patients who received no radiotherapy were studied. Thirty percent of the irradiated group had lesions of the carotid arteries that were either moderate or severe vs only 6% of the control patients. Five patients were symptomatic; all had undergone radiotherapy. Long-term follow-up with sequential duplex ultrasound examinations is indicated in patients receiving high-dose radiotherapy for head and neck tumors, to detect radiation-induced carotid artery disease and prevent late sequelae. PMID- 2205174 TI - Renal venous thrombosis in infants and children. AB - Urgent nephrectomy was once considered standard therapy for renal venous thrombosis, but recently nonoperative therapy has been advised. To examine this trend more closely, we reviewed 46 cases of renal venous thrombosis seen at the Children's Hospital of Pittsburgh (Pa) over the last 32 years. Earlier, diagnosis was frequently supported by intravenous pyelography, which was 79% accurate. More recently, sonography confirmed the diagnosis with 92% accuracy. Of 21 patients diagnosed during life, 4 were treated operatively and 3 survived. Of 17 patients treated nonoperatively, 14 (82%) survived, including 5 with bilateral disease. Since 1978, of the 10 patients treated nonoperatively, 9 have survived with no long-term morbidity. Our experience confirms that early diagnosis with sonography followed by supportive nonoperative therapy offers the best chance for success in patients with renal venous thrombosis. PMID- 2205175 TI - Friedrich Trendelenburg and the surgical approach to massive pulmonary embolism. AB - A surgical approach to embolectomy from the pulmonary artery had been worked out in laboratory animals prior to 1908 by Friedrich Trendelenburg, professor of surgery and director of the University Surgical Clinic at Leipzig, Germany. His technique was based on limited opening of the left side of the chest directly over the common or undivided pulmonary artery and encircling the proximal aorta and pulmonary artery together through the transverse sinus of the pericardium. Both vessels were to be occluded by traction on the encircling band. Emboli were to be extracted through a small pulmonary arteriotomy, which then was to be controlled by a tangentially applied clamp, while occlusion of the great blood vessels was released. Unfortunately, during the first clinical trial of the technique, the patient died because of technical difficulties. Not until 1924 was a surviving patient described, by Trendelenburg's former trainee, Martin Kirschner. PMID- 2205176 TI - Cystic teratomas of the pancreas. AB - Cystic teratomas of the pancreas constitute an extremely rare entity with only nine cases, to our knowledge, described in the world literature. Symptoms are usually due to the compressive effects of the tumor on the neighboring organs. They should be considered in the differential diagnosis of slow-growing benign pancreatic cysts. We describe a 25-year-old woman with a pancreatic teratoma who was operated on in 1976 with the diagnosis of calcified pancreatic cyst. The diagnostic and surgical procedures are described, as well as a 14-year follow-up. The previously published cases are reviewed and the differential diagnosis is discussed. Early diagnosis and the need for total tumor resection are emphasized. PMID- 2205177 TI - [Anatomy of the sinoatrial node and the supply of its vascularization in man]. AB - Seventy heart preparations of persons belonging to different sex and age have been investigated, using a complex of anatomical and histological techniques. The dimensions of the sinoatrial node (SAN) vary with age and depend on various size and form of the heart. The large atrial branch of the right and left coronary arteries supplies mainly the SAN with blood. More seldom the atrial branches of both cardiac arteries, having anastomoses, realize the SAN blood supply. The character of the SAN vascularization depends on branching variations of the atrial vessels. At the right coronary variant the sources of the SAN blood supply are the SAN branch, the right intermediate or right posterior atrial branches, and at the left coronary variant--the anterior left, the posterior left and the intermediate left atrial branches. At the even variant the SAN blood supply sources are the right intermediate and the anterior left atrial or the right posterior and the left posterior atrial branches. The data obtained can be used for comparison with the results of coronography to make a skilled analysis of clinical-roentgenological observations. PMID- 2205178 TI - [New exhibits at the Anatomy Museum of the Dnepropetrovsk Medical Institute]. PMID- 2205179 TI - Simplified technique for suturing dislocated posterior chamber intraocular lens to the ciliary sulcus. PMID- 2205180 TI - Use of apraclonidine in the treatment of acute angle closure glaucoma. PMID- 2205181 TI - New Medicare program changes tagged on OBRA 89. PMID- 2205182 TI - Cardiovascular and intraocular pressure effects and plasma concentrations of apraclonidine. AB - We performed a double-masked, crossover study comparing the cardiovascular and intraocular pressure effects of 0.5% and 0.25% topical apraclonidine hydrochloride and 0.5% timolol maleate in 20 healthy female volunteers. The contralateral effects of unilateral apraclonidine and the plasma concentrations of apraclonidine were also assessed. All measurements were done 2, 5, and 8 hours after drop instillation. A 15-minute treadmill test was performed after the 2 hour measurements. All three active medications lowered intraocular pressure comparably. There was no significant contralateral intraocular pressure effect seen with apraclonidine. The apraclonidine plasma concentrations were variable and unrelated to the amount of intraocular pressure lowering and cardiovascular parameters measured. Apraclonidine did not affect blood pressure or heart rate any differently than placebo. Timolol, however, blunted exercise-induced tachycardia. There were no significant differences in pupillary diameters or interpalpebral fissure widths among treatment groups. PMID- 2205183 TI - Accuracy of diagnosis of choroidal melanomas in the Collaborative Ocular Melanoma Study. COMS report no. 1. AB - In the 3-year period during which patients were enrolled into the Collaborative Ocular Melanoma Study, 413 eyes with clinical diagnoses of choroidal melanoma were examined histopathologically as of December 31, 1989. Four hundred eleven of these eyes were found to be diagnosed correctly. One eye, removed after preoperative external beam radiation, was found to have a hemangioma. The second eye, removed after radioactive iodine plaque placement, was described as a magnocellular nevus (melanocytoma) by four of the five pathologists on the Collaborative Ocular Melanoma Study Pathology Review Committee. The Collaborative Ocular Melanoma Study misdiagnosis rate of 0.48% is the lowest ever reported. The major challenge with regard to posterior uveal melanomas is no longer that of correct diagnosis but rather determination of the optimal treatment. PMID- 2205184 TI - Management of traumatic hemorrhagic retinal detachment with pars plana vitrectomy. AB - Traumatic hemorrhagic retinal detachment may prevent successful visual rehabilitation of eyes with severe posterior segment injury. We managed 19 consecutive cases of traumatic hemorrhagic retinal detachment with pars plana vitrectomy, scleral buckling, and fluid-gas exchange, with or without internal drainage of subretinal hemorrhage. We based our approach on the amount of subretinal hemorrhage present and the location of associated retinal breaks. Internal drainage of subretinal hemorrhage was performed in 16 eyes to allow adequate retinopexy to hemorrhagically elevated retinal breaks (9 eyes), to remove massive subretinal hemorrhage (4 eyes), and to allow intraoperative reattachment when the retina exhibited bullous retinal detachment (3 eyes). Overall, with a minimum of 6 months of follow-up, anatomic reattachment was achieved in 13 (68%) of 19 eyes, and functional success (visual acuity 5/200 or better) was achieved in 6 (32%) of 19 eyes. Anatomic failure resulted from proliferative vitreoretinopathy (4 eyes) and globe atrophy (2 eyes). Drainage of subretinal blood appeared to be beneficial for hemorrhagically elevated retinal tears to allow adequate retinopexy and may help to accomplish long-term anatomic attachment in eyes with massive subretinal hemorrhage or bullous retinal detachment. PMID- 2205185 TI - The utility of routine screening of patients with uveitis for systemic lupus erythematosus or tuberculosis. A Bayesian analysis. AB - The indications for many laboratory tests in patients with uveitis are controversial. Bayes' theorem allows a mathematical approach to the assessment of the utility of a laboratory test based on the sensitivity of the test, the specificity of the test, and the pretest likelihood that the disease the test is intended to identify is present. We have utilized Bayes' theorem to assess the utility of routine antinuclear antibody and purified protein derivative testing in patients with uveitis. Based on published data about the sensitivity and specificity of each of these tests, as well as the prevalence of systemic lupus erythematosus and tuberculosis among patients with uveitis, we calculated that a patient with uveitis and a positive antinuclear antibody test result has less than a 1% chance of having systemic lupus erythematosus and that a patient with uveitis and a positive purified protein derivative test result has a 1% likelihood of having tuberculosis. These low probabilities mean that neither test is useful in the routine evaluation of patients with uveitis, and indiscriminate use may lead to improper diagnosis, increased costs, and, occasionally, inappropriate therapy. PMID- 2205186 TI - Immunofluorescence study of corneal wound healing after excimer laser anterior keratectomy in the monkey eye. AB - We performed anterior keratectomies on six monkey eyes, four by excimer laser large-area ablation at 193 nm and two by mechanical keratectomy. Immunofluorescence was used to study the wound healing response histopathologically. The distribution of fibrinogen, fibronectin, laminin, collagen types III, IV, and VI, and keratan sulfate was determined at postoperative intervals of 24 hours, 6 days, and 1 month. At 24 hours, fibrinogen and fibronectin coated the ablated surface, but corneal epithelial cells had not yet migrated over the wound. By 6 days and persisting at 1 month, an epithelial ingrowth of seven to 10 layers, mild stromal hypercellularity, and new collagen formation were present in the repair region. At 1 month, fibrinogen, fibronectin, laminin, and type III collagen were strongly detected in the repair region. Type VI collagen was present in both normal and healed corneal stroma at all intervals, and type IV collagen was present in Descemet's membrane only. Sulfated keratan sulfate was absent from the newly synthesized collagen stroma at all intervals. Slit-lamp photographs demonstrated corneal haze in the ablation zone in all cases at 24 hours, persisting for 1 month. The fluorescence patterns produced by excimer laser ablation and mechanical keratectomy were qualitatively identical. PMID- 2205187 TI - The early diagnosis and treatment of congenital dislocation of the hip. PMID- 2205188 TI - A randomized controlled trial of extra-amniotic ethinyloestradiol for cervical ripening in multiparas. AB - A double-blind randomized controlled trial was carried out to determine if ethinyloestradiol applied extra-amniotically would ripen the unfavourable cervix at term. Twenty five multiparas were given 150 mg ethinyloestradiol gel while 25 multiparas were given gel alone. There was no difference between the ethinyloestradiol and control groups in either mean change of Bishop score or the induction-to-delivery interval. PMID- 2205189 TI - Differentiation of monochorionic and dichorionic twin placentas by antenatal ultrasonic evaluation. AB - The prenatal identification of various types of placentation is important for the antenatal management of twin pregnancies. Such classification can be achieved with the use of ultrasound examination. In 32 cases of twin pregnancy the intervening septum was classified as either a thick (dichorionic) or thin (monochorionic) type. Macroscopic and microscopic examination of the placenta after delivery confirmed the ultrasound diagnosis in 24 of the 30 cases, an accuracy of 80%. PMID- 2205190 TI - Single intrauterine fetal death in a suspected monozygotic twin pregnancy. AB - The antepartum death of a fetus in a twin pregnancy is associated with significant risk of mortality and morbidity in the surviving infant. A recent case of single intrauterine death in a suspected monozygotic twin pregnancy at a regional hospital prompted a study of similar cases in the hospital's recent experience and a review of the current literature. We report the successful conservative management of fetal death in a monozygotic twin pregnancy. PMID- 2205191 TI - Uric acid in pregnancy and preeclampsia: an alternative hypothesis. PMID- 2205192 TI - Intrauterine surgery using electrocautery. PMID- 2205193 TI - The training of the obstetrician-gynaecologist for the 21st century. PMID- 2205194 TI - Sudden infant death syndrome. PMID- 2205195 TI - Transport aircraft crew and decompression hazards: study of a positive pressure schedule. AB - The protection of the transport aircraft crew against cabin decompression hazards at high altitude (Z less than 45,000 ft) (13,700 m) is achieved by positive pressure breathing (PPB). Currently, many PPB schedules are used. Our research was performed to propose a PPB schedule, using the hypothesis of a decompression at high altitude, including a stay at the flight level and an emergency descent at the rate of 15,000 ft.min-1. The measures were arterial oxygen saturation, heart rate, speech capabilities, and psychomotor performance. The tests were conducted up to 45,000 ft. They show that the best protection at 45,000 ft is afforded when the PPB is included between 2 and 2.5 kPa (15 to 18.75 mm Hg). PMID- 2205197 TI - Special properties associated with virulence of urinary Escherichia coli. AB - Escherichia coli (E. coli) isolated from 53 urine and 26 stool samples of patients with urinary tract infection (UTI) and 50 stool samples of normal individuals were studied to see their hemolytic, hemagglutinating and 'O' antigenic properties which might be related to virulence of the organism. Significantly higher number of E. coli isolated from urine of UTI patients were found to possess hemolytic, hemagglutinating properties and more frequently belonged to certain "O" antigenic groups either singly or in combination as compared to those isolated from stool of both UTI patients and normal individuals. Hemagglutinating property appeared to be most frequently associated with UTI. PMID- 2205196 TI - Initial table treatment of decompression sickness and arterial gas embolism. AB - This descriptive, nonrandomized, multicenter-based study compares the treatment outcomes of two major categories of recompression treatment tables for recreational sport SCUBA divers suffering from decompression sickness and/or arterial gas embolism. Stratified and logistic regression analyses were used to compare the enhanced tables, which use pressures of 165 fsw (feet of salt water) or 60 fsw with extended recompression time, to the regular tables, which use pressures of 60 fsw or less without extended recompression time. A total of 113 cases were treated with enhanced tables, 54 being successes. A total of 214 cases were treated with regular tables, 135 being successes. The final logistic statistical model after adjusting for confounding factors found a significant improvement in successful treatment outcomes for divers treated with tables that use pressures of 60 fsw or less without extended recompression time (OR = 0.47, 95% CI = 0.28-0.78). PMID- 2205198 TI - Evaluation of co-agglutination (COA), counter immunoelectrophoresis (CIE), culture and direct microscopic (Dm) examination of cere-brospinal fluid (CSF) for detection of meningitis caused by common bacterial pathogens. AB - Cerebrospinal fluid from 260 children clinically diagnosed as meningitis were examined by Dm, culture, COA and CIE test. Dm revealed the presence of bacteria in 41 (15.8%) whereas culture showed growth of organism in 52 (20%) cases. COA and CIE test were done for the detection of antigen of H. influenzae, S. pneumoniae and N. meningitidis. Among the 3 methods viz. culture, COA and CIE test which were used for the detection of the above three organisms COA detected the maximum numbers (23.5%). COA test could detect antigen in both culture positive and culture negative CSF samples. COA test detected 100% of pneumococcal, 88.5% of H. influenzae and 66.7% of N. meningitidis antigens from CSF. Diagnosis by CIE in detecting H. influenzae and N. meningitidis antigens is inferior to culture and COA, whereas in detecting pneumococcal antigens CIE is superior to culture. So COA is a valuable, cheap, rapid and sensitive method for the diagnosis of meningitis caused by the above three organisms and when used along with culture 100% of cases can be diagnosed. PMID- 2205199 TI - Modification of uridine phosphorylase from Escherichia coli by diethyl pyrocarbonate. Evidence for a histidine residue in the active site of the enzyme. AB - Uridine phosphorylase from Escherichia coli is inactivated by diethyl pyrocarbonate at pH 7.1 and 10 degrees C with a second-order rate constant of 840 M-1.min-1. The rate of inactivation increases with pH, suggesting participation of an amino acid residue with pK 6.6. Hydroxylamine added to the inactivated enzyme restores the activity. Three histidine residues per enzyme subunit are modified by diethyl pyrocarbonate. Kinetic and statistical analyses of the residual enzymic activity, as well as the number of modified histidine residues, indicate that, among the three modifiable residues, only one is essential for enzyme activity. The reactivity of this histidine residue exceeded 10-fold the reactivity of the other two residues. Uridine, though at high concentration, protects the enzyme against inactivation and the very reactive histidine residue against modification. Thus it may be concluded that uridine phosphorylase contains only one histidine residue in each of its six subunits that is essential for enzyme activity. PMID- 2205200 TI - Development of the hormone-sensitive glucose transport activity in differentiating 3T3-L1 murine fibroblasts. Role of the two transporter species and their subcellular localization. AB - The development of a hormone-responsive glucose transport activity during differentiation of 3T3-L1 murine fibroblasts to an insulin-sensitive adipocyte like phenotype was studied. Glucose transport activity was insensitive to insulin or insulin-like growth factor I (IGF-I) before differentiation, and was increased by 8-10-fold after differentiation by both insulin and IGF-I via their own respective receptors. In contrast, in undifferentiated cells insulin and IGF-I stimulated a large increase of [3H]thymidine incorporation into DNA via IGF-I receptors, indicating that undifferentiated 3T3-L1 cells are equipped with fully functioning hormone (IGF-I) receptors. Thus the previously described increase in expression of insulin receptors during differentiation cannot solely account for the development of hormone-sensitive glucose transport in the 3T3-L1 cell. The total glucose transport activity reconstituted from membrane fractions was increased by about 3-fold during differentiation. In differentiated cells, more than 80% of the total reconstitutable glucose transport activity was detected in an intracellular compartment (200,000 g microsomes) as compared with about 20% in undifferentiated cells. Immunoblots with specific antiserum confirmed previous reports indicating that the adipose tissue/muscle glucose transporter (GT3) was exclusively present in the differentiated cells, whereas the erythrocyte/brain glucose transporter (GT1) was detected in both differentiated and undifferentiated cells. Upon differentiation, GT1 was redistributed from plasma membranes to the intracellular compartment. In addition, the newly formed GT3 was predominantly found (greater than 80% of total) in the microsomal fraction of differentiated cells. Both GT1 and GT3 appeared to be hormone-sensitive, since in differentiated cells insulin as well as IGF-I gave rise to their translocation from the intracellular compartment to the plasma membrane. These data suggest that, in addition to the specific expression of the GT3 transporter, the formation of a large pool of intracellular glucose transporters comprising both GT1 and GT3 contributes to the development of insulin sensitivity in the 3T3-L1 cell. PMID- 2205201 TI - Preparation and characterization of human interleukin-5 expressed in recombinant Escherichia coli. AB - The gene coding for human interleukin-5 was synthesized and expressed in Escherichia coli under control of a heat-inducible promoter. High-level expression, 10-15% of total cellular protein, was achieved in E. coli. The protein was produced in an insoluble state. A simple extraction, renaturation and purification scheme is described. The recombinant protein was found to be a homodimer, similar to the natural murine-derived protein. Despite the lack of glycosylation, high specific activities were obtained in three 'in vitro' biological assays. Physical characterization of the protein showed it to be mostly alpha-helical, supporting the hypothesis that a conformational similarity exists among certain cytokines. PMID- 2205203 TI - Insulin responsiveness in skeletal muscle is determined by glucose transporter (Glut4) protein level. AB - Glucose transport in skeletal muscle is mediated by two distinct transporter isoforms, designated muscle/adipose glucose transporter (Glut4) and erythrocyte/HepG2/brain glucose transporter (Glut1), which differ in both abundance and membrane distribution. The present study was designed to investigate whether differences in insulin responsiveness of red and white muscle might be due to differential expression of the glucose transporter isoforms. Glucose transport, as well as Glut1 and Glut4 protein and mRNA levels, were determined in red and white portions of the quadriceps and gastrocnemius muscles of male Sprague-Dawley rats (body wt. approx. 250 g). Maximal glucose transport (in response to 100 nM-insulin) in the perfused hindlimb was 3.6 times greater in red than in white muscle. Red muscle contained approx. 5 times more total Glut4 protein and 2 times more Glut4 mRNA than white muscle, but there were no differences in the Glut1 protein or mRNA levels between the fibre types. Our data indicate that differences in responsiveness of glucose transport in specific skeletal muscle fibre types may be dependent upon the amount of Glut4 protein. Because this protein plays such an integral part in glucose transport in skeletal muscle, any impairment in its expression may play a role in insulin resistance. PMID- 2205202 TI - Protein kinase C translocation in intact vascular smooth muscle strips. AB - Using intact muscle strips from the bovine carotid artery, the time course of translocation of protein kinase C (PKC) from the cytosol to the membrane fraction was measured in response to various agonists that induce contractile responses. PKC activity was assessed by Ca2+/phospholipid-dependent phosphorylation of histone. Exposure of the muscle strips to phorbol ester (12-deoxyphorbol 13 isobutyrate) induced a rapid and sustained translocation of PKC from the cytosol to the membrane fraction, and a slowly developing but sustained contractile response. Histamine induced a comparable initial translocation of PKC to the membrane which then decreased somewhat to a stable plateau significantly above basal values. Histamine also led to a rapid and sustained increase in tension. Angiotensin I, which caused a rapid but transient contraction, induced a rapid initial translocation of PKC to the membrane. The membrane-associated PKC then declined to a stable plateau significantly lower than that seen after a histamine induced response, and only slightly above the basal value. Endothelin, which induced a sustained contraction, caused a sustained translocation of PKC from the cytosol to the membrane. In contrast, although exposure to 35 mM-KCl induced a rapid and sustained contraction, it caused only a transient translocation of PKC; the membrane-associated PKC returned to its basal value within 20 min. These results demonstrate that PKC in intact smooth muscle can be rapidly translocated to the membrane and remains membrane-bound during sustained phorbol ester- or agonist-induced contractions, but that such a sustained translocation of PKC does not occur during prolonged stimulation with KCl. PMID- 2205205 TI - Mode of cleavage of pig big endothelin-1 by chymotrypsin. Production and degradation of mature endothelin-1. AB - Pig endothelin-1 [ET-1-(1-21)] seems to be produced via proteolytic processing between Trp-21 and Val-22 of an intermediate form consisting of 39 amino acid residues, termed big ET-1-(1-39), by a chymotrypsin-like proteinase. We examined the chymotryptic-cleavage sites of big ET-1-(1-39) by reverse-phase h.p.l.c. and sequence analysis, and found that chymotrypsin cleaved initially the Tyr-31-Gly 32 bond of big ET-1-(1-39), followed by cleavage between Trp-21 and Val-22. Furthermore, chymotrypsin hydrolysed the generated ET-1-(1-21), producing a single major product that had the same amino acid sequence as ET-1-(1-21) with a cleavage between Tyr-13 and Phe-14. The disulphide bridge between Cys-1 and Cys 15 remained intact. These results indicate that the conversion of big ET-1-(1-39) into ET-1-(1-21) catalysed by chymotrypsin requires hydrolysis of the Tyr-31-Gly 32 bond before that of the Trp-21-Val-22 bond, an event followed by cleavage between Tyr-13 and Phe-14 within the loop of ET-1-(1-21). Thus a chymotrypsin like proteinase might be involved not only in the production but also in the degradation of ET-1-(1-21) in vivo. PMID- 2205206 TI - [Substrate specificity of restriction endonuclease Kpn378I]. PMID- 2205204 TI - Initial glucose kinetics and hormonal response to a gastric glucose load in unrestrained post-absorptive and starved rats. AB - A gastric [U-14C]glucose load (4.8 mg/g body wt.) was delivered to unrestrained post-absorptive or 30 h-starved rats bearing peripheral and portal vein catheters and continuously perfused with [3-3H]glucose, in order to compare their metabolic and hormonal responses. In the basal state, portal and peripheral glycaemia were less in starved rats than in rats in the post-absorptive period (P less than 0.01), whereas blood lactate was similar. Portal insulinaemia (P less than 0.05) and protal glucagonaemia (P less than 0.005) were lower in starved rats, but insulin/glucagon ratio was higher in post-absorptive rats (P less than 0.005). The glucose turnover rate was decreased by starvation (P less than 0.005). After glucose ingestion, blood glucose was similar in post-absorptive and starved rats. A large portoperipheral gradient of lactate appeared in starved rats. Portal insulinaemia reached a peak at 9 min, and was respectively 454 +/- 68 and 740 +/- 65 mu-units/ml in starved and post-absorptive rats. Portal glucagonaemia remained stable, but was higher in post-absorptive rats (P less than 0.05). At 60 min after the gastric glucose load, 30% of the glucose was delivered at the periphery in both groups. The total glucose appearance rate was higher in starved rats (P less than 0.05), as was the glucose utilization rate (P less than 0.05), whereas the rate of appearance of exogenous glucose was similar. This was due to a non suppressed hepatic glucose production in the starved rats, whereas it was totally suppressed in post-absorptive rats. At 1 h after the glucose load, the increase in both liver and muscle glycogen concentration was greater in starved rats. Thus short-term fasting induces an increased portal lactate concentration after a glucose load, and produces a state of liver insulin unresponsiveness for glucose production, whereas the sensitivity of peripheral tissues for glucose utilization is unchanged or even increased. This might allow preferential replenishment of the peripheral stores of glycogen. PMID- 2205207 TI - Exercise and ventilatory chemosensitivities. AB - Although physical training does not affect CO2 chemosensitivity at rest, different kinds of physical training affect hypoxic ventilatory chemosensitivity at rest in different ways. On the other hand, a number of studies indicated that the mechanism of exercise hyperpnea is related to hypoxic chemosensitivity. PMID- 2205208 TI - Characteristics of pulmonary diffusing capacity for CO at rest and during exercise. AB - Characteristic patterns of changes in pulmonary diffusing capacity (DL) at rest and during exercise were investigated and characteristics of normal DL values concerned on sex, age, and ethnic groups were examined by viewing our studies and other reports. The relation of DL and pulmonary capillary blood volume (Vc) was represented as a logarithmic regression at rest and as a linear regression during exercise. The curve relation at rest is considered to show that the increase in Vc mainly reflects the process of transport from pulmonary capillary recruitment to pulmonary capillary dilation. The increasing rate of DL was not decreased during exercise, which seemed to be due to an increase in pulmonary blood flow accompanying exercise. The linear regression was also found between DL and oxygen intake during exercise and the slope was always constant among individuals and among subject groups. The general results concerned with sex difference in Japanese or ethnic difference between Japanese and Caucasians in both sexes could show that DL per stature was greater in males or Caucasians than in females or Japanese in young adults, however, the sex or ethnic difference disappeared in middle or old aged group. DL per alveolar volume which showed no sex or ethnic difference in young adults, was greater in middle or old aged group of females or Japanese than in that of males or Caucasians. PMID- 2205209 TI - Regulation of breathing during exercise. AB - This paper reviewed in short neural and humoral factors which might be responsible for inducing exercise hyperpnea. As one of the neural factors afferent signals which arise in the exercising limbs and are transmitted via group III or IV high threshold sensory fibres were involved. The other neural factor is command signals originating in the central nervous system and being fed onto the respiratory center. Hypothalamic locomotor region is assumed to be a possible locus to integrate these peripheral and central neural signals. There are enough evidences to believe that humoral factors mediated via cardiac output is also essential for the hyperpnea. Changes in VCO2 is well correlated with those of VE in dynamic as well as in steady-state response. Oscillations in PaCO2 can be assumed to play a role to link metabolic CO2 changes to those in ventilation. Thus, no single factor can explain the whole process of exercise hyperpnea. Poon's optimization model may give a key to integrate complicated and coflicting experimental results in a unique concept. PMID- 2205210 TI - Cardiopulmonary responses to static exercise. AB - Ventilatory and cardiovascular responses to isometric exercise, with special reference to hand-grip exercise, were reviewed. Blood flow through the forearm (FBF) during muscular contraction is dependent on relative strength to MVC (maximum voluntary contraction), duration of exercise, and hand temperature. FBF could attain steady state during exercise with intensities less than 15% MVC. Heart rate (HR) starts to increase with a latency as short as 0.4 to 0.6 sec in conscious animals and men in response to voluntary as well as electrically induced isometric exercise. This response is vagally transmitted. The sympathetic nerves mediated HR response with a longer delay is also found. Cardiac contractility is augmented via sympathetic beta-receptors during isometric exercise. With aging, HR response tends to be intensified, whereas, stroke volume response tends to be depressed. Thus increased cardiac output is resulted in elevated arterial blood pressure. Total vascular resistance is reported to be unaltered, or to increase, despite of consistent increase in muscle sympathetic activities during the isometric exercise. Ventilation is augmented during exercise, but the pattern of its response is not in full agreement among investigators. The underlying mechanisms to elicit those responses are discussed. PMID- 2205211 TI - Lactate-related factors as a critical determinant of endurance. AB - Many interrelated physiological and/or morphological factors have been demonstrated to influence endurance exercise performance. Some of these factors include skeletal musculature, running economy, maximal oxygen uptake (VO2max), maximal steady state (MSS), onset of blood lactate accumulation (OBLA), onset of plasma lactate accumulation (OPLA), and anaerobic (or lactate) threshold (AT or LT). The present paper focuses mainly on VO2max, MSS, OBLA, OPLA and LT, all of which have been postulated as a prerequisite in endurance exercise success. This paper consists of: (1) significance of La-related variables, (2) longitudinal studies, (3) comments, and (4) conclusion. Briefly, it is suggested that estimation of endurance exercise potential could be obtained with relatively high precision using laboratoriously measured La-related variables. The most critical determinant of endurance exercise performance such as marathon time is considered running velocity (V) at which LT is detected (V / LT), VO2 / LT, or V / MSS, while V / OBLA appears to be the best predictor of performance in endurance events of 16 km or shorter distances. PMID- 2205212 TI - Application of modeling to lactate kinetics in exercise. AB - The recent modeling technique to lactate (La) kinetics in exercise, and its availability, application, and limitation were summarized. Two examples were come up for discussion. One is the application of the compartment model (i.e., the description by the linear differential equations) to systemic La kinetics in exercise, and the other is the current controversy on anaerobic threshold, that is, the reexamination of the several proposed models of blood La kinetics during ramp exercise. In conclusion, considering the various limitations in current in vivo experimental approach on man, the theoretical approach with mathematical modeling, as one of the major strategies, gives full play to clarify the La metabolism in exercise. PMID- 2205213 TI - Neuromuscular regulation and metabolism during exercise. AB - This article reviews current evidence regarding neuromuscular regulation and metabolism during exercise. Particular emphases are given on the relationship between motor unit (MU) activity, including single MU analysis results and spinal alpha-motoneuron excitability, and cardio-respiratory response and blood lactate during dynamic exercise. In addition, a close physiological link between muscle energy metabolism and excitation-contraction processes (failure of one will affect the extent of the other) is summarized in the light of recent nuclear magnetic resonance (NMR) studies and results of neuromuscular disorder patients. PMID- 2205214 TI - Elicitor recognition and signal transduction in plant defense gene activation. AB - Plants defend themselves against pathogen attack by activating a whole set of defense responses, most of them relying on transcriptional activation of plant defense genes. The same responses are induced by treatment of plant cells with elicitors released from the pathogen or from the plant surface. Several plant/elicitor combinations have been used successfully as experimental systems to investigate the molecular basis of plant defense responses. Receptor-like structures on the plasma membrane of plant cells appear to bind the elicitors. Thereby, intracellular signal transduction chains are initiated which finally result in the activation of plant defense genes. A better understanding of the molecular mechanisms of early processes in plant defense responses, as provided by these studies, may in the long term help to develop environmentally safe plant protection methods for agriculture. PMID- 2205216 TI - X-ray induced inactivation of the sulfhydryl enzyme malate synthase in the presence of various additives. Probing the extent of primary and post-irradiation inactivation and repair by rapid screening on the microlevel. AB - The sulfhydryl enzyme malate synthase was inactivated by X-irradiation in air saturated aqueous solution, in the absence or presence of a variety of additives (thiols, antioxienzymes, typical radical scavengers, inorganic salts, buffer components, substrates, products, analogues). Radiation-induced changes of enzymic activity were registered immediately after stop of irradiation and in the post-irradiation period. Repair experiments were initiated by post-irradiation addition of dithiothreitol. Additionally, post-irradiation inactivation was modulated by some further additives. Probing the extent of primary and post irradiation inactivation and repair was accomplished effectively by screening experiments on the microlevel, and by derivation of normalized efficiency parameters which allowed quick comparisons of the various additives with respect to their protective and repair-promotive efficiencies. Correlations between the efficiency parameters were studied by means of binary and ternary diagrams. Most of the substances added before irradiation were found to protect the enzyme against primary and post-irradiation inactivation and to increase the reparability of the enzyme by dithiothreitol, the extent of the effects depending on the nature (and concentration) of the additives used. Our results indicate that both specific protection (by substrates, products, analogues, and by sulfhydryl agents) and scavenging are responsible for the radioprotective efficiencies of the additives. PMID- 2205215 TI - UVA-induced genetic effects of thioridazine, mesoridazine and sulforidazine: an in vitro study. AB - This in vitro study focuses on the UVA-induced reactions with DNA of thioridazine (TRZ), and two of its major metabolites (TRZ-2-sulfoxide or mesoridazine, MRZ; and TRZ-2-sulfone or sulforidazine, SRZ). TRZ binds covalently to DNA upon UVA irradiation. Under comparable irradiation conditions, MRZ binds to a lesser extent and almost no binding was observed with SRZ. Besides, photo-induced genetic effects were investigated by means of a differential DNA repair test in E. coli. The photo-induced genetic effects in E. coli decreased from TRZ, MRZ to SRZ, which corresponds with their capacity for UVA-induced binding to DNA. TRZ, MRZ and SRZ differed in their rate of photodecomposition rather than in the intrinsic reactivity towards DNA of the instable intermediates formed. Irreversible binding to DNA was also observed upon treatment with peroxidase, which is known to oxidize phenothiazines via the formation of reactive radical cation species. As both the colour of the intermediate and its reactivity towards DNA were comparable for peroxidase treatment and exposure to UVA, we assume that the radical cation is the reactive species in the latter case as well. PMID- 2205217 TI - A bi-national perspective on continuing medical education. AB - This paper presents a review and comparison of qualitative improvements in the organization, needs assessment, educational methodology, evaluation, and research in continuing medical education (CME) in the United States and Canada. Although accreditation now establishes minimal standards for CME and reduces the chances of irresponsible programs, some organizational issues (such as commercial sponsorship) and educational issues (how to "accredit" journal reading) remain unresolved. There are many examples of excellent, innovative CME programs offered by medical schools, and specialty societies have been instrumental in upgrading CME by serving as sponsors of accreditation and special projects. There is some evidence that the national health system of Canada has influenced the organization and content of Canadian CME, and these changes may soon affect U.S. programs as well. CME research has grown, with two types of research evident: the biomedical model, which assesses the efficacy of CME interventions by quantitative methods; and a model that uses grounded, ethnographic, methods to assess physician learning and performance change. Given the improvements of the past 20 years, the criticisms that focus exclusively on the lack of ideal educational planning for all CME programs are not so much wrong as dated and perhaps irrelevant. In developing their programs, CME leaders can begin to emphasize the physician learner and the clinical and social environment in which learning occurs. PMID- 2205218 TI - The financial status of U.S. teaching hospitals. PMID- 2205219 TI - Effects of pattern matching, pattern discrimination, and experience in the development of diagnostic expertise. PMID- 2205220 TI - Teaching old dogs new tricks: using cognitive feedback to improve physicians' diagnostic judgments on simulated cases. PMID- 2205221 TI - Pyrazole sulfanilamides: nitroderivatives of 1-phenyl-3-sulfanilamidopyrazole. Note XVI. AB - Synthesis and structural characterization of 3 sulfanilamido-1-phenylpyrazoles bearing on 1-phenyl group nitro substituent o-, m-, p-positioned are reported. All derivatives are analysed through 1H and 13C NMR spectroscopy. The MIC values obtained against Escherichia coli are briefly discussed in terms of structure activity relationship. PMID- 2205222 TI - Capillary zone electrophoresis in pharmaceutical analysis. AB - The paper presents a brief characterization of capillary zone electrophoresis, a modern analytical separation method with high expediency for practical applications, especially in pharmaceutical analysis. Basic theoretical considerations are presented and discussed to explain the effects of the operational parameters upon the separation efficiency and resolution of species. Descriptions of simple instrumentation and of the analytical procedure itself are given. Experimental examples are given of the separation of mixtures of pharmaceutically important compounds and of the effects of operational parameters, especially pH of BGE and voltage applied. Lastly, the practical application of CZE for analysis of isoxsuprine in commercial preparations is shown. PMID- 2205223 TI - Standardisation and validation of analytical methods in the pharmaceutical industry. AB - It is suggested a general scheme for the Validation of the analytical methods and some aspects of the parameters composing it are remarked. Furthermore, the procedure for the Standardisation is briefly discussed and it is highlighted the importance of two particular aspects (the calibration of the instruments and the Standard substances) that, even though not directly related to Validation, significantly affect its results. PMID- 2205224 TI - Extracellular haemolysin of Proteus penneri coded by chromosomal hly genes is similar to the alpha-haemolysin of Escherichia coli. AB - Extracellular haemolysin of four Proteus penneri strains was characterized as a polypeptide of approximately 110 kD. The chromosomal DNAs of these strains cleaved with Hind III showed three fragments hybridizing with a DNA probe containing cloned haemolysin (hly) genes of Escherichia coli. The results presented here suggested that the haemolysin of P. penneri strains is chromosomally determined and similar to the alpha-haemolysin of E. coli. PMID- 2205225 TI - [The determination of the sensitivity of bacteria to therapeutic drugs]. PMID- 2205226 TI - Interactions between potential anti-tumour 2,5-bis(1-aziridinyl)-1,4-benzoquinone derivatives and glutathione: reductive activation, conjugation and DNA damage. AB - The interaction between glutathione and potential anti-tumour 3,6-disubstituted 2,5-bis(1-aziridinyl)-1,4-benzoquinone (BABQ) derivatives has been studied using u.v. spectrophotometry and h.p.l.c. The formation of BABQ-glutathione adducts was demonstrated in vitro for the BABQ parent compound (TW13), triaziquone (2,3,5 tris(1-aziridinyl)-1,4-benzoquinone) and for BABQ derivatives containing halogen substituents. The clinically-used BABQ derivative diaziquone (AZQ; 2,5-bis(1 aziridinyl)-3,6-bis(ethoxycarbonylamino)-1,4-benzoquinon e) did not react with glutathione. TW13 and triaziquone markedly inactivated bacteriophage M13-DNA in the presence of glutathione. This inactivation is probably produced by reductive activation of the BABQ derivative to a DNA-alkylating semiquinone radical. However, formation of bulky glutathione adducts decreases reactivity to DNA. Halogen-substituted BABQ derivatives react rapidly with glutathione to form adducts. This appeared to prevent DNA alkylation by these compounds. Comparison of these results with in vivo and in vitro activity against tumour models (L1210) suggests that in vivo halogen-substituted BABQ derivatives are efficiently inactivated by glutathione conjugation. The differences between the halogen substituted BABQ derivatives on the one hand and TW13 and triaziquone on the other hand are probably caused by a difference in reaction mechanism with glutathione. From the viewpoint of drug design, halogen-substituted BABQ derivatives are expected to be inactive anti-tumour agents, in spite of high reactivity and activity in tumour models in vitro. PMID- 2205227 TI - Renin correlates with blood pressure reactivity to stressors. AB - This study examines the relationship between renin levels and physiologic reactivity to stressors. Seventy-five normotensive and mildly hypertensive men were studied on a high salt diet (200 mEq/day Na) and on a low salt diet (10 mEq/day Na). Renin, plasma catecholamines, heart rate, and blood pressure were examined at rest, after standing in place for 8 minutes, and after a brief mathematics task. Renin levels increased in response to the stressor tasks, particularly on the low salt diet. The change in diastolic pressure in response to the stressor tasks was correlated with the change in renin (r = 0.45, p less than 0.001) but not with the change in norepinephrine. The combination of change in renin and norepinephrine levels accounted for 21% of the variance in predicting diastolic pressure reactivity (p less than 0.0015). PMID- 2205228 TI - Breastfeeding--a litigated issue. PMID- 2205229 TI - Tongue-tie (ankyloglossia) and breastfeeding: a review. AB - Tongue-tie (partial ankyloglossia) is a congenital condition in which the membrane under the tongue is too short or may be attached too near the tip of the tongue, thereby preventing tongue protrusion. Considerable controversy among health professionals persists regarding the appropriate treatment of partial ankyloglossia. Therefore, lactation consultants need to be aware of tongue-tie and its potential negative impact on breastfeeding. This discussion examines issues relating to the possible need for treatment and the role of the lactation consultant in the evaluation and care of the infant who presents with ankyloglossia. PMID- 2205230 TI - Neonatal frenotomy may be necessary to correct breastfeeding problems. AB - A review of cases of short frenulum (tongue-tie) seen in a recent year at the Lactation Institute and Breastfeeding Clinic provides data about its relationship to sucking and breastfeeding problems such as insufficient infant weight gain and reduced milk supply, sore nipples and repeat bouts of mastitis in the mother. Frenotomy was recommended for ten of 13 babies who appeared to have a short frenulum. Three mothers chose not to hae the frenulum clipped and either gave up breastfeeding or continued to experience problems. Breastfeeding was successfully established by the five healthy babies whose frenulum was clipped. The two babies for whom frenotomy did not completely correct breastfeeding problems had severe birth defects. PMID- 2205231 TI - A general treatise of the diseases of infants and children. Collected from the best practical authors by John Pechey of the College of Physicians in London. 1697. PMID- 2205232 TI - New pressure ulcer status tool. PMID- 2205233 TI - Clinical evaluation of a polymeric membrane dressing in the treatment of pressure ulcers. AB - The healing effects of the Ferris polymeric membrane dressing were tested in a 70 day evaluation of 18 ulcers on 13 elderly subjects with Stage I, II, and III pressure ulcers. The mean length of time these ulcers had been present prior to the trial dressing was 144 days with 50% of the ulcers (n = 9) present for 75 days or longer. Over 60% of the ulcers were completely healed and over 94% were improved during the study. PMID- 2205234 TI - Mechanism of interaction of cysteine proteinases and their protein inhibitors as compared to the serine proteinase-inhibitor interaction. PMID- 2205236 TI - The squash inhibitor family of serine proteinases. PMID- 2205235 TI - Effects of autolysis on the catalytic properties of the calpains. PMID- 2205237 TI - Evidence of protease activity producing NH2-terminal truncated form of rat cystatin A in newborn rat epidermis. PMID- 2205238 TI - Expression in Escherichia coli of the AIDS virus aspartic protease through a protein fusion. AB - Fusion of the coding sequence for the aspartic protease of HIV-1, the human AIDS virus, to a bacterial beta-lactamase gene, provides an expression system in E. coli which yields high specific activity HIV protease in a soluble form. PMID- 2205239 TI - Characterization and inhibition of the retroviral HIV-proteinase. PMID- 2205240 TI - Serpins: structure and mechanism of action. AB - The Serpins are a major family of proteins, most of which are involved in the regulation of proteinase activity. Current data indicate that inhibitor function is dependent on formation of tight, but reversible binary complexes, with carbohydrate being unimportant for this function. The reaction takes place in a reactive site loop common to all Serpins, with the key residue for complex formation being in the P1 reactive site position. However, other contact residues are also involved as shown by the variation in specificity in a number of animal proteins with the same P1 residue. The role of other amino acid residues in Serpins which aid in conferring specificity has not yet been established. However, the availability of methods for obtaining site specific mutations should soon make it possible to determine other contact points required for Serpin function, thus allowing for the design of inhibitors which are singularly targeted with a high reaction rate towards a given proteinase. PMID- 2205242 TI - Common feature of the four types of protease mechanism. PMID- 2205241 TI - A new look at Pz-peptidase. AB - Work with new, quenched fluorescence substrates of Pz-peptidase has led to the discovery that Pz-peptidase, soluble metallo-endopeptidase and endo oligopeptidase A are either identical, or very closely related enzymes. Pz peptidase is a metallo-endopeptidase with marked thiol-dependence. It has been confirmed that inhibitors of the type designed by Orlowski for soluble metallo endopeptidase are effective tools in studying Pz-peptidase. There is little evidence to support the proposed role of Pz-peptidase in connective tissue matrix degradation, and the main function of the enzyme may be intracellular. PMID- 2205243 TI - Irregular elastase complexes: crystallographic and molecular dynamics studies of small inhibitors and water. PMID- 2205244 TI - A new, highly sensitive enzymic assay for human tryptase and its use for identification of tryptase inhibitors. AB - A chromogenic two-stage assay for human tryptase, a specific marker of mast cell activation, was developed based on the tryptase-induced conversion of prothrombin to thrombin. This assay proved to be more sensitive and reliable than measurements of amidolytic activity of tryptase with small synthetic substrates such as Bz-Arg-Nan and was suitable to detect tryptase activity in human body fluids. In addition, the assay was useful for studies of natural and recombinant inhibitors of tryptase. PMID- 2205245 TI - Mass spectrometric characterization of recombinant human interleukins 1 beta. AB - The cDNA coding for amino acid residues 121-269 of human interleukin 1 beta was cloned and expressed at Sclavo Research Center by C. Baldari et al. (1987, EMBO J. 6, 229-234) using Saccharomyces cerevisiae as the host cell. The purified protein showed a very low specific activity when compared to that of a mature recombinant interleukin expressed from Escherichia coli. Preliminary experiments indicated the occurrence of post-translational events in the yeast-derived protein. In an attempt to correlate the structural modifications and the biological activity of recombinant interleukins, the two proteins were characterized by fast atom bombardment mass spectrometry (FAB/MS) following the FAB-mapping procedure. The amino acid sequence of interleukin expressed in E. coli was identical to that expected whereas the mass spectrometric analysis of the recombinant S. cerevisiae protein confirmed the occurrence of covalent modifications. In particular, the asparagine residue at position 7 (numbering follows the mature active protein sequence) was shown to be glycosylated and the two cysteine residues at position 8 and 71 were involved in an S-S bridge. The results demonstrate the value of FAB/MS in the quality control of recombinant interleukins. PMID- 2205246 TI - Medium scale production of L-myo-inositol 1-phosphate. AB - L-myo-Inositol-1-phosphate synthetase was purified from baker's yeast, grown in a fermenter in an inositol-deficient medium and analyzed using a new HPLC assay for inositol. This enzyme was used in a procedure, developed from methods partially described in the literature, for the medium scale production and purification of L-myo-inositol 1-phosphate. The identity and purity of the product were confirmed by 1H and 31P NMR spectroscopy. PMID- 2205247 TI - Differential transport and integration into the nuclear lamina for lamins A, B, and C. AB - Lamins A, B, and C are the major proteins of the mammalian nuclear lamina and have been well studied in BHK-21 cells. Using in vivo labelling, cell fractionation, and immunoprecipitation, we have found that lamins have different patterns of nuclear transport and solubility. Newly synthesized lamin A is translocated to the nucleus faster than lamin C or B. It is the most tightly bound lamin and cannot be extracted from the lamina by nonionic detergent or high salt buffers. Lamins B and C migrate more slowly to the nucleus. Partitioning between cytoskeleton and detergent-soluble fractions shows that integration of lamins B and C is not completed before a 1-h chase. For lamin C this process is dependent upon protein synthesis and can be inhibited with cycloheximide. Even though lamins A and C are almost identical, lamin C is never firmly bound to the lamina and can be partially solubilized upon high-salt treatment. PMID- 2205248 TI - Evidence that mammalian ribonucleotide reductase is a nuclear membrane associated glycoprotein. AB - Epitope-specific antibodies to the M1 and M2 subunits of mammalian ribonucleotide reductase were prepared using peptides predicted to have a high antigenic index. Western blotting demonstrated that the anti-M1 antibody was specific for the 89 kilodalton M1 subunit (and its degradation fragments) and the anti-M2 antibody specifically recognized the 45-kilodalton M2 subunit. Both antibodies inhibited the CDP-reductase activity of the holoenzyme. Using these antibodies, both the M1 and M2 subunits were shown to be localized in the cytoplasm and in the nuclear regions of a number of cell types, including B77 avian sarcoma virus transformed NRK cells, T51B rat liver cells, 5123tc hepatoma cells, and rat liver cells in vivo. In addition, the M1 subunit was found to be localized as a halo around isolated rat liver nuclei. Biochemical analysis of the cytoplasmic fraction of liver cells and a Triton X-100 wash of nuclei from these cells confirmed the location of the enzyme activity in these cellular compartments. The M1 subunit appears to be glycosylated, as indicated by its retention on a Affi-Gel concanavalin A affinity column. Therefore, in mammalian cells ribonucleotide reductase appears to be not only in the cytoplasm, but is also associated with the nuclear membrane or nuclear lamina. The activity of the enzyme in the membrane fraction changes dynamically during the cell cycle. PMID- 2205249 TI - Estimation of relative mRNA content by filter hybridization to a polythymidylate probe. AB - We have developed an accurate and sensitive method for the quantitation of relative mRNA in RNA samples. This procedure is especially applicable for normalizing numerous RNA samples which are to be analyzed by dot blot hybridization. The method entails hybridization of a polythymidylate probe with RNA bound to filters. The relative hybridization of polythymidylate probe to RNA is proportional to the polyadenylate RNA content of the RNA samples. Hybridization of polythymidylate probe to RNA is not dependent on any cell treatment or growth condition that we have observed, and experimental variation is minimized. Therefore, the relative hybridization to polythymidylate probe is a better method for standardizing the amount of mRNA in RNA samples than is relative hybridization to cDNA probes such as actin or beta 2-microglobulin, whose transcript levels may vary according to cell treatment. Furthermore, since experimental variation and errors are minimized, this procedure is suitable for normalizing RNA samples in which there are only small changes in the levels of particular transcripts. PMID- 2205250 TI - Quantitation of the ras gene product in leukemic blast cells using enzymatic staining. AB - Few studies have focused on the significance of ras protein levels in human malignancy, in part because of the inherent difficulty in quantitation of the ras gene product. We have developed a method for the enzymatic determination of the ras gene product and have used this method for the quantitation of ras gene product levels in 19 patients with acute leukemia. This technique provides a practical means to assess p21 expression in leukemic cells ex vivo while avoiding the use of radioactive reagents. In addition, the mobility of the ras species of interest is determined. This assay should be easily modified for the use of other antibodies such as those reported to be specific for various ras species (i.e., H , K- and N-ras), for specific ras mutations or for other nonras proteins. Because of the use of electrophoresis prior to quantitation of protein, the antibody used does not need to possess high specificity for the protein of interest. PMID- 2205251 TI - A clonal analysis of glial lineages in neonatal forebrain development in vitro. AB - Retrovirus-mediated gene transfer combined with triple immunostaining for astro- and oligodendroglial markers (antibodies to glial fibrillary acidic protein, GD3 ganglioside, and galactocerebroside, and the O4 antibody) was used to study clonal aspects of glial lineage in primary cultures of the neonatal rat striatum. We found two major clonal populations: astrocyte clones containing GFAP+, but GD3 , O4-, and GC- cells, and oligodendrocyte clones containing cells expressing various combinations of GD3, O4, and GC, with rare GFAP+ cells. These results indicate that astrocytes and oligodendrocytes belong to separate lineages in forebrain postnatal development. PMID- 2205252 TI - [Seasonal incidence of infectious meningitis]. PMID- 2205253 TI - [Two cases of brain infarction associated with hypertriglyceridemia]. AB - We reported two cases of brain infarction. They were cousins. Case 1 was a 12 year-old girl, who complained of aphasia, dyscalculia, right-left disorientation and right homonymous hemianopsia. CT showed low density areas in left superior and middle temporal gyri. Case 2 was a 15-year-old boy, who had left hemiplegia and hypesthesia to pain, temperature and touch on the left side of the body. CT showed low density areas from the genu of the internal capsule to the corona radiata, and from the posterior portion of putamen to the posterior limb of the internal capsule on the right side. Both cases had hypertriglyceridemia which might be associated with the etiology of infarction. PMID- 2205254 TI - More on classic manuscripts. PMID- 2205255 TI - 1965-1990: 25th anniversary of nurse practitioners. A classic manuscript reprinted in celebration of 25 years of progress. The Burlington randomized trial of the nurse practitioner. 1971-2. AB - From July 1971, to July 1972, in a large suburban Ontario practice of two family physicians, a randomized controlled trial was conducted to assess the effects of substituting nurse practitioners for physicians in primary-care practice. Before and after the trial, the health status of patients who received conventional care from family physicians was compared with the status of those who received care mainly from nurse practitioners. Both groups of patients had a similar mortality experience, and no differences were found in in physical functional capacity, social function or emotional function. The quality of care rendered to the two groups seemed similar, as assessed by a quantitative "indicator-condition" approach. Satisfaction was high among both patients and professional personnel. Although cost effective from society's point of view, the new method of primary care was not financially profitable to doctors because of current restrictions on reimbursement for the nurse-practitioner services. PMID- 2205256 TI - An EXAFS study of the copper accumulated by yeast cells. AB - X-ray absorption spectroscopy has been applied to the in vivo examination of copper-resistant yeast cells. The in vivo structure of the metal-binding site of the accumulated copper has been compared to that of the purified yeast thionein. Analysis of the EXAFS spectra performed on intact yeast cells indicates that the accumulated copper is univalent and is exclusively coordinated to sulfur atoms at a distance of 219 pm with an average coordination number of 2. In contrast, the purified protein indicates a univalent copper trigonally coordinated to sulfur at a distance of 221 pm. These discrepancies are discussed in terms of copper location in the resistant yeast cells. PMID- 2205257 TI - Immunological regression of metastatic cancer in the liver as a result of "in vivo xenogenization". AB - We attempted to induce the regression of liver metastatic tumor cells in vivo by the administration to rats of Friend leukemia virus (FV) (in vivo xenogenization). The virus which was used in this experiment, FV, is highly immunogenic and does not normally cause disease in an adult rat. At first, we induced a FV viremia in tumor bearing rats in order to deliver the virus to the site of the tumor cells. FV viremia was induced by injecting 60 mg/kg cyclophosphamide (CY) i.v. after the administration of FV, and by transferring syngeneic bone marrow cells so that FV would be able to infect them and then replicate. In order that the tumor cells which were infected with virus should regress, it was necessary to break down their tolerance to FV antigens. As adoptive immunotherapy we therefore, transferred syngeneic spleen cells from rats which had been immunized with FV to tumor bearing rats. The result of this experiment was that these tumor bearing rats infected with FV which had received either normal syngeneic spleen cells or no spleen cells as controls died from liver metastasis (8 out of 9 rats (89%) and 15 out of 17 (88%) respectively). On the other hand, only 4 out of the 15 (27%) tumor bearing rats which were infected with FV and which received FV-immune spleen cells died from liver metastasis. These sets of data indicate that the in vivo xenogenization of tumor cells are indeed able to induce the regression of metastatic tumor cells. PMID- 2205259 TI - A randomized study of combined 5-fluorouracil and plasma perfusion over protein A sepharose in human advanced colorectal carcinoma. AB - To evaluate the advantage with regard to toxicity, response rate, time to progression and survival of combination chemoimmunotherapy over single-agent chemotherapy in patients with metastatic colorectal carcinoma (CRC), 30 patients were randomized to receive a combination of 5-fluorouracil (5-FU) by continuous i.v. infusion and plasma perfusion (PP) over protein A-Sepharose (group A), or a combination of 5-FU and PP over sepharose (group B) or 5-FU alone (group C). 5-FU was given at 1,000 mg/m2/d on days 1-5 of a 4-weekly cycle until progression. Patients of groups A and B received bi-weekly on-line PPs until disease progression or for a maximum of 19 treatments. PP was well tolerated and no severe or life-threatening toxicity was observed. The response rates were 10% for the group A (1 PR), 0% for the group B and 20% for the group C (1 CR + 1 PR). The times to tumor progression for patients in groups A and C were 22 months, 12 and 11 months, respectively and the median survival times were 17 months, 10 months and 9 months. Although the time to progression and survival tended to be higher in patients treated with protein A. PP, these differences were not statistically significant. This is the first report of a randomized trial showing some therapeutic advantage in combining protein A. PP with 5-FU in CRC patients. Further randomized studies are required to demonstrate the real true value of this chemoimmunotherapeutic approach. PMID- 2205260 TI - Soluble recombinant CD4--a potential therapeutic agent for HIV infection. PMID- 2205258 TI - The effect of radiation therapy combined with natural killer cells against spontaneous murine fibrosarcoma. AB - The effect of radiation therapy combined with lymphoid cells against spontaneous murine fibrosarcoma (FSa-II) was investigated both in vivo and in vitro. In the in vivo experiment, syngeneic C3H mice were divided into 3 groups. Animals in the first group were injected with 1 x 10(5) tumor cells into the right hind leg. Animals in the second and third groups were injected with 1 x 10(5) tumor cells mixed with 1 x 10(7) normal lymphoid cells (NLC) or effector lymphoid cells (ELC), respectively. ELC were obtained from spleen and lymph nodes of FSa-II bearing mice and incubated in vitro for 40 hr to eliminate suppressor T cell function. NLC were obtained from normal mice and incubated in the same way. Irradiation was given using 137Cs unit 3 days after cell inoculation. 12 out of 14 mice (85.7%) inoculated with tumor cells mixed with NLC did not show any tumor growth at 60 Gy local irradiation. 12 out of 21 mice (57.1%) inoculated with tumor cells alone and 6 out of 10 (60%) with tumor cells mixed with ELC rejected tumors at the same radiation dose. This synergistic effect with NLC was not observed when NLC was inoculated after irradiation, indicating that lymphoid cells should be in contact with tumor cells before irradiation. In the 51Cr release assay, lymphoid cells obtained from whole body irradiated (WBI) mice showed 17.8% lysis without irradiation and 28.8% lysis at 5 Gy irradiation. Untreated NLC showed almost no cytotoxic effect at the same radiation dose. This synergistic effect disappeared when WBI lymphoid cells were treated with anti asialo GM1 and complement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2205261 TI - Interleukin-2 in the treatment of HIV disease. PMID- 2205262 TI - Type I interferons (alpha and beta) in HIV disease. PMID- 2205263 TI - Nuclear protooncogene products: fine-tuned components of signal transduction pathways. PMID- 2205264 TI - The role of signal-transducing events in the proliferative response of cells to a mitogenic viral K-ras protein. AB - Activated oncogenic ras proteins are powerful mitogenic agents which by themselves can initiate and maintain the proliferation of quiescent cells in the absence of any exogenous growth factors. In an attempt to understand how ras proteins induce proliferation we examined the early events in the G0 to G1 transition caused by the activation of a thermolabile K-ras protein in quiescent, serum-starved tsKSV-transformed NRK cells. We show that ras reactivation, in the absence of exogenous growth factors, triggered a rapid surge in free cytosolic Ca2+ and diacylglycerol production, which led to a transient increase in membrane associated protein kinase C (PKC) activity which was necessary for G1 transit. Unlike TPA-stimulated PKC activity, the ras-induced increase in PKC was readily extracted from membranes by EGTA. These signal transducing events occurred despite the fact that ras activation did not induce the tyrosine phosphorylation of any known surface receptor. The results indicate that the K-ras protein triggers the G0 to G1 transition by an intracellular mechanism and not indirectly via autocrine stimulation. PMID- 2205265 TI - Stereoselective interaction of an azole antifungal agent with its target, lanosterol 14 alpha-demethylase (cytochrome P-45014DM): a model study with stereoisomers of triadimenol and purified cytochrome P-45014DM from yeast. AB - The effect of the four triadimenol stereoisomers on the purified yeast lanosterol 14 alpha-demethylase (cytochrome P-45014DM), the primary target of azole antifungal agents, was studied. (1S,2R)-Triadimenol was the most potent demethylase inhibitor and bound quantitatively to the enzyme below 0.05 microM. This isomer also interfered with the chemical reduction of cytochrome P-45014DM and the binding of CO to the cytochrome. The other isomers showed a lower inhibitory effect on the enzyme, and the order of activity was (1R,2R) greater than (1R,2S) greater than or equal to (1S,2S). Based on these findings and the reported preferred conformations for the triadimenol stereoisomers (Anderson, N.H. et al., Pestic. Sci. 15:310-316, 1984), it is predicted that orientation of the hydrophobic tert-butyl and p-chlorophenyl groups relative to the azole nitrogen is important to fit the antifungal agent in the active site of the demethylase. PMID- 2205266 TI - 2H-NMR resolution of the methylenic isotopomers of ethanol applied to the study of stereospecific enzyme-catalysed exchange. AB - We have shown that site-specific natural isotope fractionation of hydrogen studied by NMR (SNIF-NMR) is an important source of information on the mechanistic and environmental effects which govern the photosynthesis of sugars and their fermentation into ethanol. Three isotope ratios associated with the methyl, methylene, and hydroxyl sites of ethanol are determined in achiral media. In this study we show that complementary information about possible stereospecific mechanisms involving the methylenic hydrogens is also rendered accessible by 2H-NMR enantiomeric resolution. The synthesis of mandelate esters enables exchange between the pro-R site of ethanol and water to be investigated. Simultaneous access to the three site-specific isotope ratios of the ethyl group is obtained at isotopic dilutions close to the natural ones. Mediation of the exchange by the enzymic system alcohol dehydrogenase-alpha-lipoyldehydrogenase and by the yeast Saccharomyces cerevisiae are compared. The progress of the reaction can be followed quantitatively as a function of time and the occurrence of glycolytic metabolism of endogeneous materials by yeast can be substantiated in a one-pot experiment. PMID- 2205267 TI - Clostridium perfringens toxins involved in food poisoning. PMID- 2205268 TI - Clostridium botulinum toxins. PMID- 2205269 TI - Analytical methods for Staphylococcus aureus. PMID- 2205270 TI - What is the best way to diagnose renal allograft rejection in the small child? PMID- 2205271 TI - Intravenous urography with iopamidol in children with reflux and obstructive nephropathy: effects on glomerular and tubular functions and the renin angiotensin-aldosterone system. AB - Twenty-seven children [2 with chronic renal failure (CRF)] with reflux or obstructive nephropathy underwent intravenous urography with iopamidol 370, a nonionic contrast medium 1 (CM), osmolality 796 mosmol/kg, for renal growth evaluation. Mean iopamidol dosing was 1.69 ml/kg (range 1.22-2.42); the 2 children with CRF received 2 and 2.42 ml/kg respectively. One hour after infusion a significant decrease in haematocrit, haemoglobin, plasma sodium (Na+), chloride (Cl-), renin activity and aldosterone was observed, consistent with a possible plasma volume expansion due to the slightly hypertonic CM. At the same time there was a significant increase in fractional excretion of Na+, Cl- and potassium, probably due to the haemodynamic effects and tubular response to a substance acting as on osmotic diuretic. The -24 to +48 h monitoring of albuminuria, beta-2 microglobulin excretion, and in 4 children excretion of N-acetyl-beta glucosaminidase and alanine-aminopeptidase did not show any relevant nephrotoxicity. No untoward effect of clinical relevance was observed. PMID- 2205272 TI - Renal tubular acidosis. AB - The term renal tubular acidosis (RTA) is applied to a group of transport defects in the reabsorption of bicarbonate (HCO3-), the excretion of hydrogen ions, or both. On clinical and pathophysiological grounds, RTA can be separated into three main types: distal RTA (type 1), proximal RTA (type 2) and hyperkalaemic RTA (type 4). Some patients present combined types of proximal and distal RTA or of hyperkalaemic and distal RTA. Diagnosis of RTA should be suspected when a patient presents a normal plasma anion gap, and hyperchloraemic metabolic acidosis. A normal plasma anion gap (Na(+)-[Cl- + HCO3-] = 8-16 mEq/l) reflects loss of HCO3- from the extracellular fluid via the gastro-intestinal tract or the kidney, dilution of extracellular buffer or administration of hydrochloric acid (HCl) or its precursors. Distinction of RTA from other disorders is greatly facilitated by the study of the urine anion gap (Na+ + K+ - Cl-). This index estimates the urinary concentration of ammonium in a patient with hyperchloraemic metabolic acidosis. A negative urine anion gap (Cl- much greater than Na+ + K+) suggests the presence of gastro-intestinal or renal loss of HCO3-, while a positive urine anion gap (Cl- less than Na+ + K+) is indicative of a distal acidification defect. Determination of plasma potassium, of urine pH at low plasma HCO3- concentration, and of urine PCO2 and fractional excretion of HCO3- at normal plasma HCO3- concentration permits the differentiation between the various types of RTA. PMID- 2205274 TI - Immunology. Regulation of cellular function at tissue, hormonal and molecular levels. PMID- 2205275 TI - Appropriate training in paediatric nephrology for developing countries: hypothesis and proposals. AB - Appropriate training in paediatric nephrology is a comprehensive approach designed to develop skills and capabilities to deal with the following basic components of medical care: (1) medical competence for clinical and research activities; (2) interpersonal relationships directed at maintaining patients' freedom and autonomy; and (3) adequate incorporation of technological, financial and managerial aspects of paediatric nephrology services. Inappropriate training causes frequent, dramatic and paradoxical negative feedback in developing countries: shortage of functioning medical equipment, skilled manpower and trained paediatric nephrologists co-exist with unused high-cost medical equipment and loss of skilled health care professionals. Appropriate training, tailored to the needs and resources of developing countries, could be an efficient way to develop high-quality paediatric nephrology care. Efficient training must develop self-reliant, self-sufficient and skilled health care professionals in the local economic, educational, technological and political context. Regional and international co-operation is essential to promote adequate training in paediatric nephrology. Developing countries lack an effective and accurate information communication network for selecting modern technology for paediatric nephrology. The development of this network through international co-operation, is an urgent requirement. PMID- 2205276 TI - [Pioneers in pediatric medicine. Fritz Goebel (1888-1950)]. PMID- 2205277 TI - [Pioneers in pediatric medicine. Otto Soltmann (1844-1912)]. PMID- 2205273 TI - Recent advances in understanding the pathogenesis of the hemolytic uremic syndromes. AB - One of the requirements for an agent to cause hemolytic uremic syndrome (HUS) is its ability to injure endothelial cells. Shiga-like toxin (SLT) can do this. SLT is produced by Escherichia coli and Shigella dysenteriae serotype 1; both have been implicated as causes of typical HUS. Endothelial cells have receptors (GB3) for SLT and the toxin can inhibit eukaryotic protein synthesis, thereby causing cell death. Glomerular endothelial cell injury or death results in a decreased glomerular filtration rate and many of the perturbations seen in HUS. It is no longer certain that hemolysis is the result of a microangiopathy. Cell injury results in release of von Willebrand multimers; if these are ultra-large, thrombosis may ensue. There is also increasing evidence that neutrophils have a role in the pathogenesis of typical HUS. Streptococcus pneumoniae can also cause HUS and care must be taken to avoid giving plasma to patients with S. pneumoniae associated HUS. There is compelling evidence that types of HUS are inherited by autosomal recessive and autosomal dominant modes. Patients with autosomal recessive HUS may have recurrent episodes. Mortality and morbidity rates are high for the inherited forms. PMID- 2205278 TI - [Pioneers in pediatric medicine. Edmund Kerpel-Fronius (1906-1984)]. PMID- 2205279 TI - [Memories of Albert Schweitzer--where and when did tropical pediatrics start?]. PMID- 2205280 TI - [Pioneers in pediatric medicine. Carl Ludwig von Elsasser (1808-1874)]. PMID- 2205281 TI - Epidermal growth factor receptors in human epidermal tumours. AB - Immunolocalization studies using the strepavidin/biotin peroxidase system were used to identify epidermal growth factor receptors in 10 samples of normal skin, 13 seborrhoeic warts (SW), five lesions of Bowen's disease (BD), 11 solar keratoses (SK), 22 basal cell carcinomas (BCC) and five squamous cell carcinomas (SCC). The intensity of cell membrane staining was assessed using the 10-cm visual analogue scale technique and the results analysed using non-parametric statistics. The cell membranes in BCC showed significantly less intense staining when compared to normal epidermal cells (P less than 0.001) and the constituent cells of SW (P less than 0.001), SK (P less than 0.001), BD (P less than 0.01), and SCC (P less than 0.001). Classification of the specimens into normal, benign, premalignant and malignant indicated that cell membranes of malignant tumours showed significantly less staining than the other groups (P less than 0.001). The observed reduction in the epidermal growth factor receptors in malignant tumours may be due to occupation and down regulation in response to autocrine secretion of growth factors. PMID- 2205282 TI - The extension technique: a new method of demonstrating initial lymph vessels in excised human skin. AB - The initial lymph vessels, the lymph capillaries and precollectors, are difficult to detect in normal skin using routine histological methods. A method is described in which specimens of the skin are fixed in an expanded condition. In 1.05 microns thick plastic-embedded sections the dilated lymph vessels of the skin can be demonstrated. The dermal lymph vessel network can be seen following the subepidermal injection of a coloured solution. The endothelial cells and subendothelial fibrous network can be examined using electron microscopy. PMID- 2205283 TI - Protection against endotoxin-induced foetal resorption in mice by desferrioxamine and ebselen. AB - Endotoxin was administered to mice on their 13th day of pregnancy at doses which caused the resorption of approximately 50% of the implanted foetuses. The iron chelator desferrioxamine was found to significantly inhibit the percentage of resorptions induced by endotoxin in a dose-dependent manner. The highest dose of desferrioxamine (5 mg) given intravenously 30 min prior to, immediately after, and 4 and 24 h after endotoxin inoculation, reduced the percentage of resorptions from 56.9 to 17.9%. Administration of the novel selenium-containing compound ebselen, which is both an antioxidant and an inhibitor of leukotriene synthesis, was also found to significantly protect against endotoxin-induced foetal resorptions, reducing the percentage of resorbed foetuses from 52.9 to 26.0% when given at a dose of 50 mg/kg (s.c.) at the time of endotoxin inoculation and 24 and 48 h following. Both these compounds also significantly reduced the increase in spleen weights observed when the mice were given endotoxin. These results provide evidence that the iron-catalysed production of hydroxyl radicals from other oxygen-derived species and the formation of leukotrienes play an important role in the mechanism by which endotoxin causes foetal resorptions in the mouse. PMID- 2205285 TI - Pregnancy and thromboembolic disease: a literature review with implications for nursing. PMID- 2205284 TI - Kallikreins and kinins: mediators in inflammatory joint disease? PMID- 2205286 TI - The implications of introducing the symphyseal-fundal height-measurement. A prospective randomized controlled trial. AB - A total of 1639 women attending the antenatal clinic of Gentofte University Hospital, Copenhagen, during 1986-1987 was randomized into a symphyseal fundal (SF)-group and a control group. The women in the SF-group had their fundal height measured from the 29th week until delivery. The measurements were used along with the other usual screening procedures. The SF-measurements were not found helpful in the prediction of small-for-gestational-age infants and no significant differences were found between the two groups regarding the number of interventions, additional diagnostic procedures, or the condition of the newborns. PMID- 2205287 TI - New design rigid and soft vacuum extractor cups: a preliminary comparison of traction forces. AB - Women due for vacuum extraction were randomly allocated to delivery using one of two soft cups (Silc or Silastic) or two new design rigid cups (New Bird or O'Neil). Traction forces were recorded continuously and higher values were reached with the rigid than the soft cups (median 15.8, range 7.5-19.7 vs 11.1, 7.2-15.1 kg, P less than 0.01). Selection of the most appropriate vacuum cup for each clinical situation should take into account that the flexible cups are associated with less cosmetic disfigurement but have a lower capacity for traction. PMID- 2205288 TI - Accuracy of ultrasound measurements of female pelvic organs. AB - Uterine size, endometrial thickness and ovarian volume were measured ultrasonically and the results compared with caliper measurements made shortly afterwards at the time of total hysterectomy and bilateral salpingo-oophorectomy. The results establish the validity of ultrasound measurements. Histological studies also confirmed the diagnosis made with ultrasound of polycystic ovaries in women complaining of pain due to pelvic congestion. PMID- 2205289 TI - Gestrinone in the treatment of menorrhagia. AB - The role of gestrinone, 2.5 mg twice weekly, in treating proven menorrhagia (greater than 80 ml) was examined in 19 women. They were treated for five cycles (2 placebo, 3 active), taking one capsule twice weekly. Placebo had no effect on menstrual blood loss (MBL). On gestrinone 10 women became amenorrhoeic, in five MBL was markedly reduced (5-74 ml) and four did not respond. In three of the non responders submucous leiomyomas were found at subsequent hysterectomy. Follow-up periods showed a persistent reduction in MBL for nine women in the first post treatment menstruation. PMID- 2205290 TI - Unsatisfactory colposcopy and the response to orally administered oestrogen: a randomized double blind placebo controlled trial. AB - Thirty-six women with dyskaryotic cervical smears and unsatisfactory colposcopy were randomly allocated to receive either 30 micrograms ethinyl oestradiol or placebo daily by mouth for 10 days. Thirty-four women were available for review (17 women in each of the two groups), full colposcopic inspection of the transformation zone was possible in a significantly greater proportion of the oestrogen treated group (70% versus 23%, P less than 0.01). As most diagnostic conizations are currently performed on the basis of unsatisfactory colposcopy, the use of oestrogen medication followed by colposcopic reassessment should permit a reduction in the number of patients subject to operation. PMID- 2205291 TI - Maternal abdominal pressure alters fetal cerebral blood flow. PMID- 2205292 TI - Nutrient intakes, vitamin-mineral supplementation, and intelligence in British schoolchildren. AB - Children (227), aged 7-12 years, weighed and recorded all food and drink consumed for seven consecutive days. Each child completed tests of verbal and non-verbal intelligence, and was then randomly allocated to one of two groups after matching for age, sex, IQ and height. In a double-blind trial lasting for 28 d, one group received a vitamin-mineral supplement daily and the other group a placebo. On re testing, there were no significant differences in performance between the two groups. Furthermore, there was no consistent correlations between test scores and micronutrient intakes based on the weighed records. Thus, we found no evidence that learning ability in a cross-section of British schoolchildren was limited by the quality of their diets. PMID- 2205293 TI - Influence of malaria infection on peroxyl-radical trapping capacity in plasma from rural and urban Thai adults. AB - Measurement of peroxyl-radical trapping capacity (TRAP) were made in plasma from patients with malaria from a rural and an urban Thai community. The results were compared with those from control subjects living in the same areas and chosen to match the patients closely. Measurements were also made of various antioxidants including nutritional indices vitamin C and alpha-tocopherol and the non nutritional indices urate and protein-sulphydryl. Parasite counts, temperature on examination and the duration of illness were recorded together with measurements of plasma caeruloplasmin (EC 1.16.3.1), retinol and malondialdehyde (MDA). In general, most measurements made in the villagers were lower than those in the comparable urban groups. The exceptions were caeruloplasmin and MDA when the latter was expressed as MDA:cholesterol ratio. TRAP values were extremely low in 50% of the villagers and 25% of the urban patients with malaria and these results correlated with retinol and vitamin C and inversely with malonaldehyde. The results suggested that low TRAP values are associated with lipid peroxidation and that vitamin C and possibly retinol may be destroyed by the oxidative conditions present in the plasma in this disease. PMID- 2205294 TI - Effect of insulin on the utilization of propionate in gluconeogenesis in sheep. AB - The effects of insulin on the utilization of propionate in glucose synthesis were studied in fed and fasted sheep. Insulin was infused at 0.40 microU/h into the mesenteric vein. Glucose was infused to prevent hypoglycaemia. The rate of incorporation of [2-14C]propionate into glucose was determined before and during insulin infusion. After 150 min of insulin infusion endogenous glucose synthesis was about 70% of control values, whereas the incorporation of [14C]propionate into plasma glucose was 94% of control values. In contrast, the incorporation of other glucose precursors into glucose was decreased 30-50% by insulin. Therefore, insulin does not appear to decrease the utilization of propionate in gluconeogenesis. These results are consistent with the proposition that insulin differentially affects the rate of incorporation of glucose precursors into glucose in ruminant animals. PMID- 2205295 TI - High-affinity binding of water by proteins is similar in air and in organic solvents. AB - Published data for water adsorption by proteins suspended in organic solvents (of interest as enzyme reaction mixtures) have been converted to a basis of thermodynamic water activity (aw). The resulting adsorption isotherms have been compared with those known for proteins equilibrated with water from a gas phase. This comparison can show any effects of the solvent on the interaction between the protein and water at the molecular level. At lower water contents (aw less than about 0.4), similar adsorption isotherms are found in each solvent and in the gas phase; differences are probably less than the likely errors. Hence, it may be concluded that the presence of an organic solvent has little effect on the interaction between proteins and tightly bound water; on a molecular scale there is probably little penetration of the primary hydration layer by solvent molecules, even fairly polar ones such as EtOH. At higher aw values, there are differences between the isotherms which probably are significant. Nonpolar solvents increase the amount of water bound by the enzyme (at fixed aw), while polar solvents (mainly EtOH) may reduce the amount of water bound by the enzyme, presumably by occupying part of the secondary hydration layers in place of water. PMID- 2205296 TI - Lac repressor-operator interaction: DNA length dependence. AB - The interaction of the E. coli lac operon repressor with its operator DNA has been directly examined as a function of the length of operator-containing DNA. The apparent bimolecular association rate constants were calculated as ka = (kd/KD), where the dissociation equilibrium constant, KD and the dissociation rate constant, kd, were measured by nitrocellulose filter adsorption assays. The values obtained for the overall association rate constants are compared with theoretical association rate curves for specific mechanisms. Association of the repressor with short operator containing DNA fragments (less than 70 base pairs) occurs at rates expected of three-dimensional diffusion. Our data also imply that at longer DNA lengths a combination of three-dimensional diffusion with one dimensional sliding along with hopping and/or intersegment transfer must be involved to facilitate the repressor operator association. PMID- 2205297 TI - Expression of the copy DNA for human A4 and B4 L-lactate dehydrogenases in Escherichia coli. AB - The human LDH-A and LDH-B cDNAs, containing the coding regions for the L-lactate dehydrogenase A4 (M) and B4 (H) polypeptides respectively have been cloned into Escherichia coli to place the cDNAs under the control of hybrid E. coli/Bacillus stearothermophilus transcriptional and translational signals. Human A4- and B4 isoenzymes are produced in E. coli cells harbouring the expression plasmids pHLDHA22 and pHLDHB10 at levels of 6.5 and 1.5% of the soluble protein of the cell, respectively. The tac promoter of these vectors was not induced by isopropyl beta-D-thiogalactopyranoside. The A4 and B4 human isoenzymes synthesized in E. coli were purified to homogeneity and show the same properties as isoenzymes isolated from human tissue. The amino acid sequences of 12 N terminal residues of the human isoenzymes synthesized in E. coli were determined to be identical to those deduced from the DNA sequence of the cloned cDNAs except that the N-terminal methionine was absent from both. However, in contrast to LDH made in human cells, acetylation of the N-terminal alanine does not take place in E. coli cells. PMID- 2205298 TI - Integrating music in breathing training and relaxation: I. Background, rationale, and relevant elements. AB - Quasiformal reports of widespread use of music in counterarousal techniques abound despite little evidence of its psychophysiological effects. Some known effects are presented here, and they suggest, among other things, an influence on hemispheric dominance, changes in autonomic nervous system activity, and relaxation by paradoxical arousal patterns contrary to those in cognitive function and anxiety. Hypothetical subcortical reflexes are postulated as mediators. Different types of music and their effect are described. Of particular relevance is that some forms of music have been reliably shown to have a profound beneficial effect on breathing. PMID- 2205299 TI - Applied psychophysiology and biofeedback of event-related potentials (brain waves): historical perspective, review, future directions. AB - This paper reviews the efforts of workers in the 1960s-1980s to demonstrate voluntary control of exogenously evoked (event-related) potentials in visual, somatic sensory, and auditory systems in rats, cats, and humans. The first part of the paper reviews the conceptual foundation and development of the work--it actually arose from traditional sensory coding and neural correlates of behavior studies. The second part summarizes recent applications of the method in the area of pain control. In reviewing these matters, the major effort is directed at revealing how the ideas unfolded in very human, day-to-day, anecdotal terms. There is not much of an attempt to formally review the literature, which is cited for consultation elsewhere. In the same spirit, many possible future experiments are suggested by way of elucidating the key remaining questions in the area. PMID- 2205300 TI - Implantation of porous acrylic cement in soft tissues: an animal and human biopsy histological study. AB - Long-term (8 and 24 month) reactions of the (hypo) dermis of the guinea pig to solid and porous (50 vol%) acrylic implants and four human biopsies from porous subcutaneous acrylic implants were studied light microscopically. The solid implants were encapsulated by dense connective tissue. Mobility was evidenced by the loss of 4 out of 36 after 2 yr and was considered the explanation for the occurrence of ectopic cartilage and mineralized material at some solid implants' surfaces after 2 yr. A dense capsule was not evident with the porous implants, instead vascularized collagenous connective tissues penetrated into and filled the pores, thus anchoring the implant to the body. None of these implants, was lost. Notwithstanding the presence of some multinucleated giant cells, scattered inflammatory cells and loosely packed inflammatory foci with both implant materials, the materials were considered well-tolerated by the body. The histology of the human biopsy did not differ significantly from the porous animal implants. PMID- 2205301 TI - Laser-induced damage to transparent polymers: chemical effect of short-pulsed (Q switched) Nd:YAG laser radiation on ophthalmic acrylic biomaterials. I. A review. AB - The use of short-pulsed lasers in ophthalmic surgery inspired and called for research on the damage inflicted by the laser radiation upon the acrylic polymers from which artificial intraocular lenses are made. The possible release of toxic monomers by laser-induced depolymerization is of great concern but past investigations of this phenomenon have been very limited. The present knowledge of various types of laser-induced damage to transparent polymers is reviewed with particular emphasis on the acrylic materials and intraocular lenses. PMID- 2205302 TI - The evolution of heteromorphic sex chromosomes. AB - The facts and ideas which have been discussed lead to the following synthesis and model. 1. Heteromorphic sex chromosomes evolved from a pair of homomorphic chromosomes which had an allelic difference at the sex-determining locus. 2. The first step in the evolution of sex-chromosome heteromorphism involved either a conformational or a structural difference between the homologues. A structural difference could have arisen through a rearrangement such as an inversion or a translocation. A conformational difference could have occurred if the sex determining locus was located in a chromosomal domain which behaved as a single control unit and involved a substantial segment of the chromosome. It is assumed that any conformational difference present in somatic cells would have been maintained in meiotic prophase. 3. Lack of conformational or structural homology between the sex chromosomes led to meiotic pairing failure. Since pairing failure reduced fertility, mechanisms preventing it had a selective advantage. Meiotic inactivation (heterochromatinization) of the differential region of the X chromosome in species with heterogametic males and euchromatinization of the W in species with heterogametic females are such mechanisms, and through them the pairing problems are avoided. 4. Structural and conformational differences between the sex chromosomes in the heterogametic sex reduced recombination. In heterogametic males recombination was reduced still further by the heterochromatinization of the X chromosome, which evolved in response to selection against meiotic pairing failure. 5. Suppression of recombination resulted in an increase in the mutation rate and an increased rate of fixation of deleterious mutations in the recombination-free chromosome regions. Functional degeneration of the genetically isolated regions of the Y and W was the result. In XY males this often led to further meiotic inactivation of the differential region of the X chromosome, and in this way an evolutionary positive-feedback loop may have been established. 6. Structural degeneration (loss of material) followed functional degeneration of Y or W chromosomes either because the functionally degenerate genes had deleterious effects which made their loss a selective advantage, or because shorter chromosomes were selectively neutral and became fixed by chance. 7. The evolutionary routes to sex-chromosome heteromorphism in groups with female heterogamety are more limited than in those with male heterogamety. Oocytes are usually large and long-lived, and are likely to need the products of X- or Z-linked genes. Meiotic inactivation of these chromosomes is therefore unlikely. In the oocytes of ZW females, meiotic pairing failure is avoided through euchromatinization of the W rather than heterochromatinization of the Z chromosome.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2205303 TI - Development and evolutionary origins of vertebrate skeletogenic and odontogenic tissues. AB - This review deals with the following seven aspects of vertebrate skeletogenic and odontogenic tissues. 1. The evolutionary sequence in which the tissues appeared amongst the lower craniate taxa. 2. The topographic association between skeletal (cartilage, bone) and dental (dentine, cement, enamel) tissues in the oldest vertebrates of each major taxon. 3. The separate developmental origin of the exo- and endoskeletons. 4. The neural-crest origin of cranial skeletogenic and odontogenic tissues in extant vertebrates. 5. The neural-crest origin of trunk dermal skeletogenic and odontogenic tissues in extant vertebrates. 6. The developmental processes that control differentiation of skeletogenic and odontogenic tissues in extant vertebrates. 7. Maintenance of developmental interactions regulating skeletogenic/odontogenic differentiation across vertebrate taxa. We derive twelve postulates, eight relating to the earliest vertebrate skeletogenic and odontogenic tissues and four relating to the development of these tissues in extant vertebrates and extrapolate the developmental data back to the evolutionary origin of vertebrate skeletogenic and odontogenic tissues. The conclusions that we draw from this analysis are as follows. 8. The dermal exoskeleton of thelodonts, heterostracans and osteostracans consisted of dentine, attachment tissue (cement or bone), and bone. 9. Cartilage (unmineralized) can be inferred to have been present in heterostracans and osteostracans, and globular mineralized cartilage was present in Eriptychius, an early Middle Ordovician vertebrate unassigned to any established group, but assumed to be a stem agnathan. 10. Enamel and possibly also enameloid was present in some early agnathans of uncertain affinities. The majority of dentine tubercles were bare. 11. The contemporaneous appearance of cellular and acellular bone in heterostracans and osteostracans during the Ordovician provides no clue as to whether one is more primitive than the other. 12. We interpret aspidin as being developmentally related to the odontogenic attachment tissues, either closer to dentine or a form of cement, rather than as derived from bone. 13. Dentine is present in the stratigraphically oldest (Cambrian) assumed vertebrate fossils, at present some only included as Problematica, and is cladistically primitive, relative to bone. 14. The first vertebrate exoskeletal skeletogenic ability was expressed as denticles of dentine. 15. Dentine, the bone of attachment associated with dentine, the basal bone to which dermal denticles are fused and cartilage of the Ordovician agnathan dermal exoskeleton were all derived from the neural crest and not from mesoderm. Therefore the earliest vertebrate skeletogenic/odontogenic tissues were of neural crest origin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2205304 TI - An attempt at a rational classification of theories of ageing. PMID- 2205305 TI - Molecular basis of homing of intravenously transplanted stem cells to the marrow. PMID- 2205306 TI - A phase I/II trial of recombinant granulocyte-macrophage colony-stimulating factor for children with aplastic anemia. AB - Nine pediatric patients (median age, 8 years; range, 0.7 to 19 years), eight with refractory aplastic anemia and one with newly diagnosed aplasia, were enrolled in a phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) administered via continuous intravenous infusion. Doses ranged from 8 to 32 micrograms/kg/d. Six of eight evaluable patients responded with a significant rise in neutrophil count (median fourfold increase; range, 2.5- to 31 fold) during the 28-day induction period. Five patients completed 2 further months of therapy (maintenance) with persistent or improved neutrophil responses. Three patients had bone marrow aspirates suggestive of increased erythropoiesis, although only one patient had improvement in peripheral hematocrit and platelet count. In the five patients completing maintenance, three experienced a rapid return to baseline counts after rhGM-CSF was discontinued, one maintained a neutrophil response for 2 months after drug discontinuation, and one has maintained a trilineage response for greater than 1 year off study. Drug therapy was well tolerated. Toxicity was minimal at doses from 8 to 16 micrograms/kg/d. Fever and rash were more commonly seen at 32 micrograms/kg/d. No patient developed an infection during the course of rhGM-CSF administration. These results demonstrate that rhGM-CSF increases peripheral neutrophil counts in children with refractory and newly diagnosed aplastic anemia and may be able to stimulate a multilineage response in a more limited number. Randomized, prospective trials are necessary to determine if rhGM-CSF administration will impact favorably on the morbidity and mortality of severe aplastic anemia. PMID- 2205308 TI - Ultrastructural localization of a macrophage-restricted sialic acid binding hemagglutinin, SER, in macrophage-hematopoietic cell clusters. AB - Resident bone marrow macrophages in hematopoietic clusters have previously been shown to express a novel lectin-like sheep erythrocyte receptor, SER, which mediates binding of unopsonized sheep erythrocytes via recognition of sialylated glycoconjugates and may interact with sialylated ligands on murine bone marrow cells. In this study, the distribution of SER on macrophages within hematopoietic clusters was localized by a monoclonal antibody, SER-4, by immunofluorescence and immunoelectron microscopy. SER was found to be diffusely localized at the contact zones between macrophages and erythroblasts, whereas the receptor was highly concentrated at the contacts between macrophages and developing myelomonocytic cells. These data suggest that SER on resident bone marrow macrophages interacts differentially with sialylated ligands on developing myeloid cells and that this may influence their development. PMID- 2205307 TI - Enhancing and suppressing effects of recombinant murine macrophage inflammatory proteins on colony formation in vitro by bone marrow myeloid progenitor cells. AB - Purified recombinant (r) macrophage inflammatory proteins (MIPs) 1 alpha, 1 beta, and 2 were assessed for effects on murine (mu) and human (hu) marrow colony forming unit-granulocyte-macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-E) colonies. Recombinant MIP-1 alpha, -1 beta, and -2 enhanced muCFU-GM colonies above that stimulated with 10 to 100 U natural mu macrophage-colony stimulating factor (M-CSF) or rmuGM-CSF, with enhancement seen on huCFU-GM colony formation stimulated with suboptimal rhuM-CSF or rhuGM-CSF; effects were neutralized by respective MIP-specific antibodies. Macrophage inflammatory proteins had no effects on mu or huBFU-E colonies stimulated with erythropoietin (Epo). However, natural MIP-1 and rMIP-1 alpha, but not rMIP-1 beta or -2, suppressed muCFU-GM stimulated with pokeweed mitogen spleen-conditioned medium (PWMSCM), huCFU-GM stimulated with optimal rhuGM-CSF plus rhu interleukin-3 (IL 3), muBFU-E and multipotential progenitors (CFU-GEMM) stimulated with Epo plus PWMSCM, and huBFU-E and CFU-GEMM stimulated with Epo plus rhuIL-3 or rhuGM-CSF. The suppressive effects of natural MIP-1 and rMIP-1 alpha were also apparent on a population of BFU-E, CFU-GEMM, and CFU-GM present in cell-sorted fractions of human bone marrow (CD34 HLA-DR+) highly enriched for progenitors with cloning efficiencies of 42% to 75%. These results, along with our previous studies, suggest that MIP-1 alpha, -1 beta, and -2 may have direct myelopoietic enhancing activity for mature progenitors, while MIP-1 alpha may have direct suppressing activity for more immature progenitors. PMID- 2205309 TI - RAS mutations are rare events in Philadelphia chromosome-negative/bcr gene rearrangement-negative chronic myelogenous leukemia, but are prevalent in chronic myelomonocytic leukemia. AB - Previous reports have indicated that mutations of the RAS oncogenes are not associated with the chronic phase of Philadelphia chromosome-positive chronic myelogenous leukemia (Ph1+ CML). However, further studies were needed to determine their association with Ph1- CML and chronic myelomonocytic leukemia (CMML). Therefore, 6 patients with Ph1- CML who were also negative for BCR rearrangements (Ph1-/BCR- CML) and 30 patients with CMML were analyzed for the presence of RAS oncogene point mutations to determine the similarities of these diseases at the molecular level. The assay used the polymerase chain reaction for amplification of the target RAS sequences and panels of specific synthetic oligonucleotide probes for hybridization to wild type and/or mutated sequences. None of the six Ph1-/BCR- CML patients had mutations in the RAS oncogenes, while 17 of 30 (57%) of the CMML patients had RAS oncogene mutations. Eighty percent of the mutations involved substitution of aspartic acid for glycine (G----A) in the 12th or 13th codons of N-ras or K-ras. Furthermore, although not statistically significant, survival studies raise the possibility of shortened survival in patients with RAS oncogene point mutations, with the average survival being 33 months for Ph1-/BCR- CML, 35 months for CMML without point mutations, and 11 months for CMML with RAS mutations. Thus, RAS mutations appear to be associated with CMML and not Ph1-/BCR- chronic phase CML, there is a high propensity for the K-ras or N-ras mutations to involve an G----A substitution in the 12th or 13th codons, and RAS mutations in CMML may relate to prognosis and require further studies. PMID- 2205310 TI - Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro. AB - Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria. PMID- 2205312 TI - [Cardiotoxicity of continuous intravenous infusion of 5-fluorouracil: clinical study, prevention and physiopathology. Apropos of 13 cases]. AB - 5-Fluorouracil (5FU) cardiotoxicity is thought to be an infrequent toxic effect, usually related to coronary vasospasm. Among 198 patients (pts) receiving 5FU as a continuous infusion (CI) over 96 or 120 h, at a daily dose of 1,000 mg/m2, 13 new cases of 5FU--cardiotoxicity are reported. In all cases but 1, cardiovascular symptoms occurred at the first 5FU-CI course, with mean time of onset of 3 d. Chest pain was the prominent inaugural symptom with angor pectoris (6 pts) and pericarditis (3 pts). Five pts developed cardiogenic shock, which was irreversible in 3 cases. The severity of such an evolution requires prompt 5FU discontinuation, if symptoms occur, and careful hemodynamic supervision during 5FU therapy. One patient experienced typical myocardial infarction, another one epicardo myocardiopathic process with adiastolia. Disorders of repolarisation on electrocardiographic tracing were the prominent abnormalities, associated with a significant increase of QT segment in 3 cases. Re-introduction of 5FU-CI resulted in chest pain recurrence in 2 out of 4 pts, despite calcium antagonist "prevention". In our retrospective study, the incidence of 5FU-CI cardiotoxicity is 6.5%, which is consistent with recent reports (10%). Whether 5FU-induced cardiotoxicity mechanism is related to vasospastic or direct effect remains unclear. However, our series suggests a 5FU-induced post ischaemic myocardial dysfunction as described in the "stunned myocardium" syndrome. PMID- 2205311 TI - [4 years after Chernobyl: medical repercussions]. AB - The nuclear accident at Chernobyl accounted for an acute radiation syndrome in 237 persons on the site. Triage was the initial problem and was carried out according to clinical and biological criteria; evaluating the doses received was based on these criteria. Thirty one persons died and only 1 survived a dose higher than 6 Gy. Skin radiation burns which were due to inadequate decontamination, greatly worsened prognosis. The results of 13 bone marrow transplantations were disappointing, with only 2 survivors. Some time after the accident, these severely irradiated patients are mainly suffering from psychosomatic disorders, in the USSR, some areas have been significantly contaminated and several measures were taken to mitigate the impact on population: evacuating 135,000 persons, distributing prophylactic iodine, establishing standards and controls on foodstuff. Radiation phobia syndrome which developed in many persons, is the only sanitary effect noticed up to now. Finally, in Europe, there was only an increase in induced abortions and this was totally unwarranted. If we consider the risk of radiation induced cancer, an effect might not be demonstrated. PMID- 2205313 TI - Atrazine soil residue analysis by enzyme immunoassay: solvent effect and extraction efficiency. PMID- 2205314 TI - Confirmation of the enantiomers of 1-methyl-1,2,3,4-tetrahydroisoquinoline in the mouse brain and foods applying gas chromatography/mass spectrometry with negative ion chemical ionization. AB - With the aid of a new chiral derivatizing reagent and a sensitive and specific assay using capillary gas chromatography/negative ion chemical ionization mass spectrometry, the proportions of R and S enantiomers of 1-methyl-1,2,3,4 tetrahydroisoquinoline (1MeTIQ) in mammalian tissues and foods were studied. R- and S-1MeTIQ enantiomers derivatized with a chiral derivatizing reagent, perfluoro-2-propoxypropionylchloride, were clearly separated. The ratio of enantiomers was R/S = 0.24, 0.55 and 0.60 in wine, cocoa and mouse brain. S 1MeTIQ predominated in all samples. This result suggested that 1MeTIQ could be formed at least partially through an enzymatic mechanism. PMID- 2205315 TI - Hereditary (primary) haemochromatosis. PMID- 2205316 TI - Sleep disorders in children. PMID- 2205317 TI - Medical termination of pregnancy. PMID- 2205319 TI - Detection of endometrial cancer in postmenopausal women by transvaginal ultrasonography and colour flow imaging. PMID- 2205318 TI - Short course chemotherapy for tuberculous lymphadenitis in children. AB - OBJECTIVE: To assess the efficacy of a short course chemotherapy regimen for treating tuberculosis of the lymph nodes in children. DESIGN: Open, collaborative, outpatient clinical trial. SETTING: Outpatient department of the Tuberculosis Research Centre, paediatric surgery departments of the Institute of Child Health and Hospital for Children and the Government Stanley Hospital, Madras, South India. PATIENTS: Children aged 1-12 years with extensive, multiple site, superficial tuberculous lymphadenitis confirmed by biopsy (histopathology or culture). INTERVENTIONS: Patients were treated with a fully supervised intermittent chemotherapy regimen consisting of streptomycin, rifampicin, isoniazid, and pyrazinamide three times a week for two months followed by streptomycin and isoniazid twice a week for four months on an outpatient basis. Surgery was limited to biopsy of nodes for diagnosis and assessment. MAIN OUTCOME MEASURES: Response to chemotherapy was assessed by regression of lymph nodes and healing of sinuses and abscesses during treatment and follow up. Compliance with treatment and frequency of adverse reactions were also estimated. RESULTS: 197 Patients were admitted to the study and 168 into the analysis. The regimen was well tolerated and compliance was good with 101 (60%) patients receiving the prescribed chemotherapy within 15 days of the stipulated period of six months. Those whose chemotherapy extended beyond that period received the same total number of doses. Clinical response was favourable in most patients at the end of treatment. Sinuses and abscesses healed rapidly. Residual lymphadenopathy (exceeding 10 mm diameter) was present in 50 (30%) patients at the end of treatment; these nodes were biopsied. Fresh nodes, increase in size of nodes, and sinuses and abscesses occurred both during treatment and follow up. After 36 months of follow up after treatment only 5 (3%) patients required retreatment for tuberculosis. CONCLUSION: Tuberculous lymphadenitis in children can be successfully treated with a short course chemotherapy regimen of six months. PMID- 2205321 TI - ABC of major trauma. Paediatric trauma: primary survey and resuscitation--II. PMID- 2205320 TI - The Black report on socioeconomic inequalities in health 10 years on. PMID- 2205322 TI - The new activism: federal health politics revisited. PMID- 2205324 TI - Providing medical care for the poor: a proposal. PMID- 2205323 TI - Entitlement to health services reappraised. PMID- 2205325 TI - Epidermoid cyst of the spleen: a case report and review of the literature. PMID- 2205326 TI - Magnetic resonance imaging, computed tomography and endosonography in the local staging of carcinoma of the cervix. AB - Thirty-seven patients with carcinoma of the cervix were prospectively staged by examination under anaesthesia (EUA), transvaginal and transrectal ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). Pathological correlation was available for 20 patients. In the pathologically staged patients, EUA agreed with the staging in 17, understaging three patients. Endosonography agreed with the staging in 19, CT in 16 and MRI in 18 patients. For the remaining 17 patients, endosonography agreed with the EUA findings in 13, CT in 12 and MRI in 12. This study has shown that endosonography and MRI are more accurate than CT in the local staging of carcinoma of the cervix. Computed tomography was least accurate in staging early tumours and differentiating between Stage Ib and IIb disease. Lymph node involvement was detected with equal frequency by both CT and MRI. Magnetic resonance imaging was useful in identifying vaginal and bladder wall involvement and in one patient showed features due to an unsuspected early pregnancy. PMID- 2205327 TI - Radiological anatomy of the kidney revisited. AB - In recent years some structures or features such as the "inter-renuncular septum", the "echogenic triangle" and the "echogenic line" have been described to support the concept of a kidney resulting from the fusion of two masses or renunculi. To clarify this concept and to understand the meaning of the above echographic features better, the authors have examined prospectively by sonography the kidneys of 50 children, 200 adults with a single collecting system, 25 adults with a duplicated collecting system and 32 cadavers. Furthermore, to help explain the sonographic features, we have examined 32 cadaver kidneys with sonography and 10 cadaver kidneys with magnetic resonance imaging (MRI). The sonographic, MRI and anatomical correlations have shown that the "echogenic triangle" and the "echogenic line" are not renuncular residuals, but simply an extension of the hilar fat visible when the renal sinus is rather deep. The intermediate cortical mass is not a septum dividing the kidney into an upper and lower renunculus, but a column of parenchymal tissue crossing the renal sinus, which, from an anatomical point of view, is an accessory renal lobe. The presence of two renunculi, suggested in a previous study with cortical nephrotomography, has not been confirmed. PMID- 2205328 TI - Ultrasound as part of a 1-day gastroenterology clinic: advantages and problems. AB - Ultrasound was introduced into a 1-day gastroenterology clinic so that clinical assessment, endoscopy and ultrasound could be performed as appropriate in a single hospital visit. The findings in 602 patients are reported. A total of 256 (43%) patients underwent ultrasound, 35% of which showed positive findings including cholelithiasis in 12% and tumours in 7%. This system of referral for ultrasound is very convenient for patients and their general practitioner and is less costly than traditional referral methods. It is, however, time-consuming for the radiologist. PMID- 2205329 TI - Comparison of iopromide and iopamidol in left ventricular angiography and in coronary angiography. AB - A double blind randomized trial of two non-ionic contrast media--iopamidol and iopromide--was performed on 101 patients undergoing left ventriculography and coronary angiography. Both products performed well in the trial and there were no statistically significant differences in side effects, cardiovascular parameters, blood analysis or film quality between the two products. PMID- 2205331 TI - Ultrasonic detection of a retroperitoneal haematoma causing duodenal obstruction following ureterolithotomy. PMID- 2205330 TI - Pelvic congestion in women: evaluation with transvaginal ultrasound and observation of venous pharmacology. AB - Fourteen women with chronic pelvic pain due to congestion underwent transvaginal ultrasound scanning to observe changes in the diameters of dilated pelvic veins. Spontaneous fluctuations were observed, and intravenous dihydroergotamine resulted in a consistent venoconstrictor response (p = 0.0021) during 20 min observation. Transvaginal ultrasound is useful for imaging dilated pelvic veins and for the study of venous pharmacology. PMID- 2205333 TI - Ultrasound of the normal thymus in the infant: a simple method of resolving a clinical dilemma. PMID- 2205332 TI - "The Dormouse is asleep again" said the Hatter, and he poured a little hot tea upon its nose (Lewis Carroll). PMID- 2205335 TI - Autologous bone marrow transplantation in the treatment of acute myeloid leukemia: the Dartmouth experience and a review of literature. AB - Autologous bone marrow transplantation is increasingly being investigated as a treatment for patients with acute myelogenous leukemia. Review of the literature demonstrates that much of the data are incomplete. Most reports contain small numbers of patients, making analysis of any particular regimen difficult to assess. The morbidity and mortality of the procedure appear to be substantially less than that seen in the allogeneic setting. The major complications relate to problems with engraftment. Recovery of platelet production to normal levels is frequently cited as delayed, and in some patients, does not occur. This phenomenon may be heightened by marrow manipulation during purging or posttransplant drug therapy. It is not known if this is a problem related to stem cells or related to the changes in the hematopoietic microenvironment. The results of autologous bone marrow transplantation for patients with acute myeloid leukemia suggest that, as with standard chemotherapy, there is little survival benefit when patients are in relapse at the time of transplantation. There are few long-term survivors, and relapse within 5 months is the rule. It should be noted that the vast majority of the studies reported here have used marrow that has not been treated in an attempt to remove occult leukemia cells. The use of purged bone marrow has not yet been adequately studied. In patients in second or subsequent remission, ABMT appears to offer a chance for long-term survival not seen with present second-line standard chemotherapy regimens and should be considered a viable option for patients under the age of 55. The results to date do not define whether marrow purging is beneficial, and most studies being carried out at the present time are not evaluating this question. The majority of studies are examining different methods of purging. The result of our study in patients in second and third remission using in vitro purging of bone marrow with monoclonal antibodies PM-81 and AML2-23 are encouraging, as are the studies of purging with 4-HC. The Cancer and Leukemia Group B has just begun a study for patients with AML in second remission using the protocol we piloted at Dartmouth. We are also evaluating the feasibility of using this therapy in patients at the time of first relapse, as studies in the allogeneic setting have suggested the results are similar to those achieved in second remission (60).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2205334 TI - Phase II trial of methylglyoxal-bis(guanylhydrazone) (MGBG) in patients with refractory multiple myeloma: an Eastern Cooperative Oncology Group (ECOG) study. AB - Twenty patients with refractory multiple myeloma were treated with methylglyoxal bis(guanylhydrazone) (MGBG), an inhibitor of polyamine synthesis. MGBG 500 mg/m2 was administered on days 1 and 8, and then every 14 days. The dose was escalated to 600 mg/m2 on day 22, as tolerated. Of 14 evaluable patients, none met ECOG criteria for an objective response. The major toxicity was hematologic and related infections. MGBG demonstrated insufficient activity in the treatment of refractory multiple myeloma to warrant further study. PMID- 2205336 TI - Randomized clinical trials and the problem of suboptimal care: an overview of the controversy. PMID- 2205337 TI - Cancer immunology: highlights of the NCI Extramural Immunology Program. AB - The long-term goal of research supported by the Immunology Program is to better understand immune mechanisms and their regulation in order to develop more effective strategies to strengthen the immune response against cancer. While there has been much progress in the field of immunology in recent years, many major questions remain unanswered. The role of MHC antigens in regulating the immune response to tumors is still unclear, as is the nature of putative tumor associated antigens which are the targets of this response. The efficacy of various immune cell subsets in tumor cell killing is differentially affected by changes in tumor cell surface MHC antigen expression. Furthermore, although we now know much more about the cellular interactions in the immune response, little is actually known about the particular cell subsets which participate in an immune response is regressing versus progressing tumors. Interleukins have been shown to stimulate a variety of immunes response, and some of these immune modulators are now being tested in clinical trials, in various stages, to determine their antitumor effects. However, systemic administration of large quantities of interleukins can result in very different effects than those created by the local release of effector molecules from specific T-cell populations. Effector T cells can deliver lymphokines to precise target structures, whereas systemically administered lymphokines would affect preferentially those cells expressing the largest numbers of high affinity receptors for the lymphokines. The specificity of lymphokines as mediators of immunologic response rests largely or exclusively in the local release of such materials by T cells upon activation by antigen: MHC complexes on a stimulating cell. Because lymphokines show specificity only for nonantigen-specific, non-MHC restricted receptor molecules on target cells, the effect of lymphokine injections is likely to be determined solely by the expression of these receptors. Thus, lymphokines function well as effector molecules in a number of specific immune reactions, but it remains to be determined whether they will be useful in regulating immune responses in specific disease situations. It may be critical to recruit specific immune cells to the area of tumor growth where they, in turn, can release lymphokines to activate appropriate antitumor effector cells. Adoptively transferred T cells of the helper phenotype can induce an effective antitumor immune response in recipient mice.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2205338 TI - Prognostically significant skin window reactivity to breast cancer: influence of adjuvant therapy with retinol and tocopherol. PMID- 2205339 TI - Tumor-specific BCG therapy in colon cancer. PMID- 2205340 TI - Monoclonal antibody therapy in intra-abdominal malignancies. PMID- 2205341 TI - Therapeutic uses of macrophage colony-stimulating factor. PMID- 2205342 TI - Digoxin and angiotensin converting enzyme inhibitors in chronic heart failure. AB - "The addition of angiotensin converting enzyme inhibitors to digoxin and diuretics is effective in improving and prolonging the lives of patients with severe heart failure. Our next goal is to prevent the progression of heart failure in patients with asymptomatic left ventricular dysfunction." PMID- 2205343 TI - Pathophysiology and prevention of congestive heart failure. PMID- 2205344 TI - Postoperative infections: general principles and considerations. AB - Every surgeon should have a thorough knowledge and awareness of the general principles of postoperative infections. The key to postoperative infections is in their prevention. Even with the most prudent and ardent regimens, however, postoperative wound infections will occasionally occur. Thus, the aforementioned knowledge will allow an improved clinical acumen and permit the early diagnosis of postoperative infection. Early and vigorous local wound care combined with systemic antibiotics are necessary to minimize the potentially debilitating sequelae of the postoperative wound infection. PMID- 2205345 TI - The radiographic presentation of osteomyelitis in the foot. AB - Numerous authors have described the radiographic findings associated with osteomyelitis. Knowledge of these findings and their presentation radiographically may make diagnosis of this pathology quite simple. The challenge comes not in diagnosing osteomyelitis based on gross radiographic evidence; by this time, the disease has significantly progressed. The challenge is to be able to recognize early, subtle changes, and, in conjunction with clinical findings, to diagnose and treat the disease before classic radiographic evidence is demonstrated. PMID- 2205346 TI - Soft-tissue infection in lower-extremity trauma. AB - Soft-tissue infection after lower-extremity trauma has not been studied in detail in light of recent data on the biology of infection. This article examines specific problems in lower-extremity trauma that allow the wound to become susceptible to wound infection. It also illustrates the various principles of wound management in lower-extremity trauma that serve to prevent infection. Two case examples are used to illustrate principles of management. Other wound problems in lower-extremity trauma are also discussed, such as rabies, necrotizing soft-tissue infection, tetanus, and diabetic foot infections. PMID- 2205347 TI - Microbiology and antimicrobial therapy of diabetic foot infections. AB - Infections of the foot in the person with diabetes are the result of a complex myriad of pathophysiologic alterations. Neuropathy, vascular disease, and host immune alterations all interact to present a fertile ground for significant microbiologic invasion. When infection occurs, it is commonly due to a mixed flora of aerobic and anaerobic organisms, although "pure" aerobic or anaerobic infections are sometimes seen. Treatment of these infections requires a broad approach, including surgery, local care, and antibiotics. Most often, treatment against aerobic and anaerobic pathogens will be necessary. These infections can be divided into two categories based on clinical appearance. Severe life- or limb threatening infections can present with massive cellulitis of the foot and leg, high fever, significantly elevated white blood count, septicemia, and tissue gas. Appropriate antibiotics in this setting include either combination or single agent therapy. Imipenem/cilastatin offers coverage of all usual pathogens along with potentially lower toxicity and lower cost than combinations. Combinations containing clindamycin and aztreonam or ciprofloxacin may be useful for patients allergic to beta-lactam antibiotics. Less severe infections can usually be treated with a single-agent antibiotic such as ticarcillin/clavulanic acid or ampicillin/sulbactam. Cephalosporins with anaerobic activity, including cefoxitin, cefotaxime, and ceftizoxime, can be used in areas where enterococci are not a major problem. PMID- 2205348 TI - The role of hyperbaric oxygen therapy in the treatment of diabetic foot ulcers and refractory osteomyelitis. AB - The use of hyperbaric oxygen therapy in the care of the diabetic patient with nonhealing ulcers, refractory osteomyelitis, or both of the lower extremity can be a valuable adjunct in their overall treatment. Adequate tissue oxygenation to promote wound healing and stimulate cellular defenses can be achieved in a hyperbaric environment. Several clinical studies have supported its use in select patients. PMID- 2205349 TI - Functional reconstruction after ablative debridement for severe diabetic foot infection. AB - Managing limb-threatening diabetic infections imposes a significant strain on both physician and patient. Patient disclosure must be thorough before undertaking the task. The possibility of prolonged hospitalization, multiple surgical interventions, prolonged rehabilitation, and the potential for loss of limb must be discussed. Patient attitude and cooperation are requisite to a favorable outcome. A staged protocol must be observed. Initial surgical debridement, local wound care, and appropriate medical management to eradicate the infectious process must precede the functional reconstruction. Surgical reconstruction should use the simplest method available that will result in a durable and functional closure. Even with the best result, the patient will forever be at a functional disadvantage with the potential for future recurrence. Appropriate accommodative footwear must be instituted to augment pressure distribution on the compromised extremity. Routine reevaluation in addition to patient education is the best assurance for a favorable, sustained outcome. PMID- 2205350 TI - Use of antibiotic-loaded bone cement in the management of common infections of the foot and ankle. AB - Antibiotic-loaded bone cement is a useful adjunct in the management of chronic osteomyelitis and in the prevention of recurrent osteomyelitis after an initial attack. Additionally, antibiotic-loaded bone cement stimulated the formation of granulation tissue in excess of that which would normally be expected. Our experience has been consistent with others' experience, which suggests that the use of antibiotic-loaded bone cement is an effective means of reducing the length of hospitalization and the cost usually associated with traditional methods in the management of bone and soft-tissue infections. PMID- 2205351 TI - Ankle arthrodesis in the presence of continuous sepsis. Indications, methods, and results. AB - On 26 patients, 28 ankle fusions were performed and followed 2 or more years. A functional limb salvage was gained in 25 limbs (96%) with an overall arrest rate of 92%. There was one amputation (4%). The major complication rate was 38% for the series and 86% for patients with uncorrected wound-healing deficiencies (B hosts). All of the first and second treatment failures were associated with a central column deficiency (C-). PMID- 2205353 TI - Survival of diffuse large cell lymphoma. A multivariate analysis including dose intensity variables. AB - Ninety-five newly diagnosed patients with diffuse large cell lymphoma (DLCL) treated by cyclophosphamide (CTX), doxorubicin (ADM), vincristine (VCR), and prednisone (CHOP regimen) chemotherapy were evaluated for survival factors including dose intensity (DI). DI calculations were done for the initial cycles needed to achieve maximal response. The medians of the relative DI for CTX, ADM, and VCR were 0.9, 0.86, and 0.79, respectively. The median of the average relative DI (ARDI) was 0.83 (range, 0.28 to 1.14). The univariate analysis of potential prognostic variables showed that the following significantly decreased the survival rate: age older than 60 years (P = 0.0005), Stage III to IV (P = 0.02), male sex (P = 0.03), and all four DI variables (CTX, ADM, VCR, and ARDI) less than the median (P = 0.01 to 0.0001). A multivariate analysis by the stepwise proportional hazards model of Cox indicated that the factors predicting a poor prognosis were ARDI less than the median (P = 0.0003) and age older than 60 years (P = 0.02). A multivariate survival analysis of those who achieved complete remission showed ARDI less than the median (P = 0.0003), CTX less than the median (P = 0.02), and Stage III to IV (P = 0.02) to be the most negative factors regarding survival. In conclusion, a high DI in the initial cycles of CHOP chemotherapy for DLCL has a significant positive impact on survival. PMID- 2205352 TI - The role of timing of high-dose cytosine arabinoside intensification and of maintenance therapy in the treatment of children with acute nonlymphocytic leukemia. AB - The Children's Cancer Study Group instituted a pilot study to investigate the use of high doses of cytosine arabinoside (AraC) in the intensification phase of treatment for acute nonlymphocytic leukemia (ANLL). Patients achieving remission and not eligible for allogeneic bone marrow transplantation were treated with four doses of high-dose AraC and L-asparaginase. These drugs were repeated either on or after 28 days (q28 days), after recovery of hematologic parameters (for the first 49 patients entered onto this trial); or after 7 days (q7 days), despite dropping blood counts (for the last 53 patients enrolled). After completing an additional 3 months of intensification therapy, patients were then allocated by physician choice to either discontinue therapy or receive 18 28-day cycles of maintenance therapy, including the daily administration of 6-thioguanine. Despite three deaths associated with the toxicity of the aggressive (q7 days) AraC timing, patients receiving this approach demonstrated equal or better disease free survival from the end of induction (55% versus 42% actuarially at 3 years [P = 0.52]). Maintenance therapy appeared to play no role in improving outcome for people who received the aggressive timing of AraC cycles. Fifty-nine percent were alive disease free actuarially at 3 years from the decision to not give maintenance therapy (n = 27) compared with 62% for those receiving maintenance therapy (n = 16; P = 0.49). On the other hand, patients who received the less aggressive AraC intensification timing (q28 days) had an improved survival rate if maintenance therapy was administered (n = 17) (65% versus 39% for patients not receiving maintenance therapy [n = 24] at 3 years [P = 0.07]). Maintenance therapy therefore may not improve outcome in patients receiving aggressive timing of high-dose AraC but may be important in less intensive postremission regimens in childhood ANLL. PMID- 2205354 TI - Favorable prognosis associated with hyperdiploidy in children with acute lymphocytic leukemia correlates with extra chromosome 6. A Pediatric Oncology Group study. AB - Pretreatment bone marrow cytogenetic studies were included for 1664 patients with acute lymphoblastic leukemia (ALL) accrued to Pediatric Oncology Group (POG) 8035 laboratory classification study from May 1981 through January 1986. There was a significant difference (P = 0.0001) in distribution of stem-line karyotype (normal, hypodiploid, pseudodiploid, or hyperdiploid) among children with early pre-B, pre-B, or T-cell ALL, with early pre-B patients demonstrating a higher proportion of hyperdiploid karyotypes with modal chromosome numbers greater than 51. Cytogenetic classification of 1216 patients with early pre-B or pre-B ALL evaluable for duration of event-free survival (EFS), with median follow-up of 42 months, showed a significant prolongation of five-year EFS associated with hyperdiploidy greater than 51 (75%; standard error [SE] = 5%) compared with hyperdiploidy 47 to 51 (46%; SE = 7%), hypodiploidy (55%; SE = 11%), and pseudodiploidy (45%; SE = 7%) (P = 0.0001). Five-year EFS was intermediate for patients with normal (58%), constitutionally abnormal (66%), or unsuccessful analyses (66%). The breakpoint defining hyperdiploidy associated with better prognosis was best defined as greater than 51 (P = 0.0002). Of 239 children with hyperdiploid karyotypes, analysis of the contribution of each chromosome to EFS duration showed a significant association between improved EFS and additional chromosome(s) six (P = 0.02). Chromosome translocation was associated with shorter EFS (P = 0.0001). PMID- 2205355 TI - Extranodal non-Hodgkin's lymphoma of the head and neck. A clinicopathologic study in the Kyoto-Nara area of Japan. AB - The clinicopathologic features of 114 Japanese patients with extranodal non Hodgkin's lymphoma of the head and neck region were analyzed. The median age was 60.5 years and the male:female ratio was 1.5:1. The most common site of involvement was Waldeyer's ring, followed by the oral cavity, thyroid gland, paranasal sinuses, nasal cavity, and larynx. Seventy-five percent of the patients were in Stage I or Stage II at admission. Histologically, diffuse lymphoma accounted for 94% and follicular lymphoma for 6% of cases. The histologic grade according to the Working Formulation System of the National Cancer Institute was low in 11%, intermediate in 75%, and high in 14% of cases. Immunohistochemical study showed that the majority of the cases were of B-cell type and only 13 cases (11%) were of the T-cell type. Peripheral T-cell lymphomas (eight cases) mainly occurred in the nasopharynx and nasal cavity, whereas four of five thymic T-cell lymphomas were found in the palatine tonsil. The over-all 5-year survival rate was 54%, and the factors affecting survival were sex, histologic grade, T/B phenotype, clinical stage, and the site of initial presentation. Five-year survival with nasal cavity and Waldeyer's ring lymphoma was 24% and 46%, respectively. The poor prognosis of lymphomas at these sites might result from the predominance of T-cell lymphoma, the paucity of low grade lymphoma, and the relatively high incidence of cases that were in an advanced stage at presentation. In Stage II, patients treated with combined therapy tended to have a better 5-year survival rate than those treated with radiotherapy alone. PMID- 2205356 TI - Prognostic implications of glial fibrillary acidic protein containing cell types in oligodendrogliomas. AB - In oligodendroglial tumors the intermediate filament glial fibrillary acidic protein (GFAP) may be expressed by cells with the morphologic characteristics of typical oligodendrocytes (gliofibrillary oligodendrocytes [GFOC]) and by miniature forms of gemistocytes (minigemistocytes) as well. These latter cell types have been regarded as transitional cells that represent intermediate forms between an oligodendroglial and an astrocytic phenotype. Furthermore, in oligodendrogliomas GFAP may be expressed by intermingled classic large gemistocytes, which are not considered transitional cells. In a retrospective study of 111 oligodendrogliomas, the presence of the various GFAP-positive cell types was correlated with the survival rates of the patients. Therefore, GFAP expression was visualized with the use of an indirect conjugated peroxidase method. The survival times of the patients were recorded and statistical comparisons were made. The percentage of GFAP-positive tumor cells is increased in oligodendrogliomas of 28 patients who underwent a second biopsy (all these patients had been treated with radiation therapy as well). It was found that neither the presence of GFOC nor that of minigemistocytes is predictive of the survival. In contrast, patients with classic gemistocytes had survival lengths approximately twice as short as those of patients who did not have these cells in their tumors. No clear correlation was found between tumor grading or any of the individual histopathologic features with the presence of the various GFAP positive cell types. The ominous sign of the presence of gemistocytes in oligodendrogliomas confirms some earlier reports about the prognostic significance of this cell type in astrocytomas. PMID- 2205357 TI - Squamous cell carcinoma in epidermolysis bullosa. Treatment with systemic chemotherapy. AB - Dystrophic epidermolysis bullosa is associated with a high incidence of cutaneous squamous cell carcinoma. Despite aggressive surgical treatment, metastases occur frequently, and survival is generally poor. Chemotherapy for advanced disease has usually been avoided because of the potential for severe cutaneous toxicity. Two patients with autosomal recessive dystrophic epidermolysis bullosa and advanced squamous cell carcinoma are described. Both received cisplatin-based systemic chemotherapy without significant toxicity. PMID- 2205359 TI - The biology of metastatic breast cancer. AB - Early detection and surgical removal of breast cancer are most effective in managing a disease that may affect up to one in ten women in North America and Western Europe. However, one of the most important prognostic indicators for breast cancer is the presence of neoplastic cells in the axillary lymph nodes. The dissemination of cells from a primary lesion, resulting in the progressive growth of metastatic carcinoma in distant sites (including bone, lungs, liver, and brain) is the most common cause of death in breast cancer patients. Experimental studies on the biology of metastatic breast cancer have used rodent tumor systems, and, in recent years, the transplantation of human breast carcinoma cells into athymic mice. The results of such studies, combined with clinical observations, suggest that metastasis is not a random event. The formation of secondary lesions is the result of a sequence of selective events. A better understanding of the metastatic phenotype from cellular and molecular analyses will provide a basis for rational approaches to preventing and treating this most lethal aspect of breast cancer. PMID- 2205358 TI - A controlled trial of megestrol acetate on appetite, caloric intake, nutritional status, and other symptoms in patients with advanced cancer. AB - This double-blind, cross-over trial was designed to assess the effects of megestrol acetate (MA) on cancer-induced cachexia. Forty consecutive malnourished patients with advanced non-hormone-responsive tumors receiving no antineoplastic treatment were randomized to receive MA 480 mg/day versus placebo for 7 days. During day 8, a cross-over was made until day 15. Appetite, pain, nausea, depression, energy, and well-being were assessed with a visual analog scale (0 to 100 mm) at 9:00 AM and 4:00 PM during days 6, 7, 13, and 14. Weight (W;kg), tricep skinfold (TS; mm), arm circumference (AC; cm), and calf circumference (CC; cm) were measured at days 1, 8, and 15. Caloric intake (CI; Kcal/day) was determined during days 6, 7, 13, and 14. In 31 evaluable patients, the percentual difference in appetite at 9:00 AM, appetite at 4:00 PM, energy, and well-being after MA was +15.1, +14, +3.2, and +5.2, versus -12 (P = 0.03), -5.1 (P = 0.015), -10 (P = 0.024), and -8.3 (not significant) after placebo. Percentual difference in W, TS, AC, and CC after MA was +0.2, +1, -0.1, and +0.4 versus -0.8 (P = 0.03), -0.8 (P = 0.001), -0.3 (not significant), and -0.5 (P = 0.04) after placebo. CI during MA was 3480 +/- 1574 (48-hour intake), versus 2793 +/- 1542 (P less than 0.001) during placebo. Patients and investigators blindly chose MA in 20 (66%, P = 0.023) and 28 cases (92%, P less than 0.001), placebo in eight and two cases, and made no choice in three and one cases, respectively. Toxicity consisted of mild edema and nausea in three and two cases, respectively. After mean follow-up of 27 +/- 13 days, on an open basis, an average increase in W and AC of 4.8 +/- 1.7 kg and 2.8 +/- 1.7 cm was observed, respectively. The authors conclude that MA is a powerful appetite stimulant with subjective and objective effects on nutritional status. PMID- 2205360 TI - Nutrition and breast cancer. AB - International comparisons have provided striking correlations between fat consumption and risk of breast cancer, but these comparisons do not often consider variations in life style. Case-control studies carried out in several countries showed no real association between fat intake and breast cancer. There is some evidence that vitamin A or carotenoid intake may exert a protective effect. Alcohol intake, on the other hand, seems to be positively associated with breast cancer risk. Elevated body weight, body mass, stature, and frame size have been found to be associated as risk factors for breast cancer in women. Animal studies found that caloric restriction inhibits growth of spontaneous and induced mammary tumors, an observation that held up even when the calorie-restricted animals ingest more fat than the ad-libitum-fed controls. College women who exercise have a lower incidence of breast cancer than their more sedentary classmates. Exercise is another means of reducing caloric availability. PMID- 2205361 TI - Anatomic markers of human premalignancy and risk of breast cancer. AB - Epithelial hyperplasia of the breast carries an increased likelihood of carcinoma development, with most lesions best understood as markers of higher risk. The indication of increased cancer risk for more worrisome or complex histologic patterns has been supported in many studies. About 25% of women who underwent biopsies in the premammographic era had well-developed hyperplastic changes associated with an elevated risk of 1.5 to 2.0 times that of the general population when age and length of time of follow-up were considered. Somewhat fewer than 5% of women had specific patterns of atypical hyperplasia (AH) that approached the criteria of carcinoma in situ (CIS). These women with AH had a risk of cancer four to five times that of the general population, or about one half the risk associated with microscopic CIS. Only ductal CIS should be considered without question to be an intrinsic precancerous lesion because of its regular association with recurrence at the site of its initial diagnosis. Further studies indicated an appreciable interaction between AH and other nonanatomic risk factors, particularly a family history of breast cancer. Also, lower dosage estrogen replacement after menopause does not affect risk in any histologically defined group. The atypical hyperplastic lesions are more common in women undergoing biopsies on the indication of mammographic calcifications than because of palpable masses. The primary therapeutic implications of these premalignant lesions are intensified breast cancer surveillance and screening for these patients. PMID- 2205362 TI - Issues in mammography. AB - The goals of screening mammography are reproducibly optimum images, accurately interpreted, at the lowest possible cost. This can reduce the mortality from breast cancer. Despite this, screening mammography has not been widely used because of the controversy over the age at onset and interval of screening, charge for the examination, misinformed primary care physicians, uninformed women, and other factors. The American College of Radiology's educational efforts and mammography accreditation program are overcoming some of these obstacles. PMID- 2205363 TI - Evaluation and management of breast abnormalities. AB - The increasing use of screening mammography, liability risks, and volume control legislation by the federal government pose a major challenge to clinicians to safely select patients for breast biopsy. Despite a normal mammogram, a palpable breast mass often requires aspiration or excisional biopsy. Careful clinical judgement must prevail if observation is elected. A biopsy should be performed on a clinically suspicious mass whether the mammogram is suspicious or not. Management of the patient with a nonpalpable mammographic abnormality requires a close working relationship among the surgeon, pathologist, and radiologist. Thoughtful clinical judgement and interdisciplinary cooperation promote an acceptable benign to malignant ratio for breast biopsies. PMID- 2205364 TI - Screening mammography. Medical legal considerations. AB - The effort to respond to a public health mandate in screening nearly 50 million women in this country on a regular basis requires a departure from customary notions regarding diagnostic radiographic imaging. The screening mammogram, limited in both scope and interpretation, may be done in an efficient, rapid, throughput manner so long as it satisfies appropriate imaging parameters and reasonable interpretation. More time-consuming, deliberate approaches are reserved for patients with specific clinical or mammographic abnormalities. Successful practices will distinguish between these two efforts and plan accordingly. PMID- 2205366 TI - The role of the pathologist in breast cancer management. AB - The pathologist is a consultant in breast cancer patient management whose first responsibility is to establish the histologic diagnosis of cancer as well as its anatomic extent when sufficient tissue has been provided. The consultation also provides data that may be used to aid in selecting primary or adjuvant therapy, evaluating new therapies, estimating prognosis and assessing outcome. Examples of such data are the TNM histopathologic classification of the anatomic extent of the cancer used for the stage grouping (T: the extent of the primary tumor; N: the absence or presence and extent of regional lymph node metastasis; M: the absence or presence of distant metastasis), size, histologic type, histologic and/or nuclear grade, blood vessel and lymphatic vessel invasion assessment, steroid receptor analysis, and other special studies as appropriate. PMID- 2205365 TI - Medical and legal implications of screening and follow-up procedures for breast cancer. AB - Grievances result from false expectations on the part of both practitioners and patients when a disease treatment problem is unsolved because of biological variations in the disease itself. Widely publicized screening and follow-up recommendations are often the source of the grievances. Even when recommendations are followed exactly, bad outcomes are still associated with incurable cancer even though a fatal outcome is inevitable. Patients must be told about treatment prospects including limitations of efficacy, so that patient expectations will be realistic. Otherwise, practitioners may find themselves involved in lawsuits alleging deviation from case standards for an adverse outcome actually attributable to the nature of the cancer. Because screening and follow-up techniques continue to control treatment of breast cancer, such lawsuits are common. When ineffective treatment exists, there often are adverse harm/benefit considerations and high costs, particularly when screening or follow-up are practiced defensively, without hard data proving the value of a strategy. This article will review these problems, placing specific emphases on screening and follow-up procedures and on strategies for breast cancer. Factors that limit efficacy and increase both cost and diagnosis-associated morbidity will also be explored. PMID- 2205367 TI - Surgical management of stage I and stage II breast cancer. AB - Patients with Stage I or II breast cancer are candidates for either modified radical mastectomy or breast preservation, with limited resection of the primary, axillary dissection, and breast irradiation. Overall survival rates with these two approaches are comparable in retrospective reviews and in ongoing clinical trials. Longer follow-up has confirmed earlier findings. Patients should be given these options by surgeons, radiation therapists, and other physicians involved in their care. Not all breast cancer patients will choose breast preservation, and not all are candidates for it due to tumor-related and other factors. Patient selection criteria are discussed, and optimal surgical techniques are reviewed. PMID- 2205368 TI - Breast cancer adjuvant therapy. AB - Combined modality trials in early breast cancer have been underway since the 1960s and results are available to indicate varying degrees of success in Stage I and II. The trials have involved more than 29,000 women in 61 randomized trials. The recommendations can be summarized by stage, estrogen receptor (ER) status, and menopausal status. In Stage II patients, chemotherapy has an impact on disease mortality for ER-positive and ER-negative premenopausal women and possibly ER-negative postmenopausal patients. In postmenopausal Stage II ER positive patients, tamoxifen given for more than 2 years has a beneficial effect on survival. In node-negative patients, the major effects have been on improving disease-free survival (DFS) rather than overall survival. Tamoxifen has a positive effect in ER-positive patients while chemotherapy benefits ER-negative patients. In at least one trial chemotherapy benefitted women with ER-positive tumors, both premenopausal and postmenopausal, with lesions larger than 3.0 cm. Ongoing trials are designed to answer questions regarding optimal therapy for varying subsets including those tumors in which ER cannot be measured. New prognostic features used to determine therapy include flow cytometry studies of DNA synthesis and oncogene expression. PMID- 2205369 TI - Comprehensive management of locally advanced breast cancer. AB - The definition of locally advanced breast cancer includes patients with large tumors, extensive regional lymph node involvement, or direct involvement of the skin or underlying chest wall. Most of these patients have very poor survival with standard treatment modalities, and over the past 20 years combined modality therapy has been used to improve local and systemic control. There is limited information suggesting that patients with operable locally advanced breast cancer have an improved survival if treated with surgery (or radiation therapy) followed by systemic chemotherapy, as compared with patients treated with local modalities alone. Uncontrolled trials strongly suggest that patients with any stage of locally advanced breast cancer achieve high response rates after induction chemotherapy. Most of these patients can be rendered disease free after combined modality therapy, and their disease-free and overall survival rates appear to be improved when compared with historical controls. These results are most impressive for patients with inflammatory breast cancer, a disease previously found to be uniformly lethal when treated with local modalities of therapy alone. More recently, 30% to 50% of these patients were alive and disease free 5 years after diagnosis, and a substantial percentage were in the same condition 10 years later. Combined modality therapies are the most appropriate approach to patients with locally advanced breast cancer. Much additional research must be done to improve the results of these therapies and maximize the survival of patients with locally advanced breast cancer. PMID- 2205370 TI - Symptoms and rehabilitation needs of patients with early stage breast cancer during primary therapy. AB - The treatment for women diagnosed with early breast cancer is complex, dynamic, and controversial. More choices are available for local control and indications for systemic adjuvant therapy have changed dramatically. Knowledge of predictable physical and psychological responses through the various phases of primary treatment is the first critical element for the rehabilitation of these oncology patients. The health care provider can then anticipate problems, prepare the patient with accurate information, and institute interventions early to minimize symptoms. Information and psychological needs dominate the diagnostic phase, during which communication and emotional support are of paramount importance for decision making. Psychological distress persists through the treatment phase regardless of the choice of mastectomy or breast conservation surgery with radiation. The physical symptoms of these choices are similar, primarily related to the axillary lymph node dissection. Fatigue, breast soreness, sensation, and skin changes are common symptoms with breast irradiation that resolve over time. Nausea, vomiting, fatigue, hair loss, menopausal symptoms, and weight gain are predictable chemotherapy-related side effects and are reported as mild to moderately distressful by the majority of patients. Consistency of information, support, collaboration, coordination of care, and communication among patients and health care providers are essential to meet the challenge of successful treatment and rehabilitation. PMID- 2205371 TI - Breast reconstruction after mastectomy. Recent advances. PMID- 2205372 TI - Quality of life issues in patients with disseminated breast cancer. AB - Over half the women treated for breast cancer will experience advanced disease, and issues related to quality of life are particularly important. This article has reviewed components of quality of life specific to women with advanced breast cancer following two clinical courses:those who develop a recurrence and those who present with advanced disease. It is clear that additional research is warranted on the quality of life in women with advanced breast cancer. Work to date has clearly indicated that the management of women with advanced disease requires the resources available from a multidisciplinary perspective. Efforts to manage advanced breast cancer must include both current medical therapies and attention to the critical factors associated with enhancing the quality of their lives. Of final concern is the relationship of social class to advanced disease. Following Freeman's recent outline of the agenda for the American Cancer Society, more attention must be given to people who are economically disadvantaged because cancer incidence and mortality are greater among poor people than among the affluent. It is possible that over 50% of women presenting with advanced cancer of the breast are economically disadvantaged. Validation of this problem through research should lead to prevention programs targeted to this population. Women with breast cancer who are economically disadvantaged may be particularly receptive to interventions that will enhance their quality of life. PMID- 2205374 TI - Conservative surgery and radiotherapy for early breast cancer. AB - In 1984, as part of a prior American Cancer Society National Conference on Breast Cancer, the authors reported on the status of conservative surgery (CS) and radiotherapy (RT) as primary local treatment for women with early stage breast cancer. Since that time, additional data have become available regarding the use of this approach and its comparability to mastectomy. In general, these data support the use of CS and RT and, as a result, this approach is now more widely employed in the United States and abroad than it was in 1984. The current focus of inquiry has shifted from whether or not CS and RT is an acceptable option for patients with early stage breast cancer to the following questions. For which patients are CS and RT suitable? What are the best techniques of surgery and RT? Are there any patients who can be treated safely with CS without RT? How should RT and systemic therapy be integrated when both are to be used? In this report, recent results on the use of CS and RT from both retrospective and prospective trials are summarized, and these current areas of inquiry are addressed. PMID- 2205373 TI - Facilitating emotional coping during treatment. AB - Patient resources for coping with breast cancer can be enhanced by attention to cognitive, affective, psychosomatic, and social components of the illness. The diagnosis and treatment of breast cancer constitutes an immediate confrontation with mortality, and sympathetic but direct examination of the patient's vulnerability and means of coping with it will reduce rather than amplify death anxiety. The development and pursuit of realistic goals influenced by the prognosis can help patients adjust constructively. Extremes of emotion are to be expected at times, but persistent depression and/or anxiety should be vigorously treated, including the use of appropriate psychoactive medication when the symptoms are primarily somatic (e.g., sleep disturbance and reductions in energy). Physical symptoms such as pain, nausea, and vomiting can be controlled by teaching patients such techniques as self-hypnosis, biofeedback, and systemic desensitization. Finally, a feeling of social isolation is the rule, not the exception, with cancer patients. Group and family treatment can effectively counter this. Systematic studies of such treatment interventions have shown favorable results, including significant reductions in mood disturbance and pain. PMID- 2205375 TI - Comprehensive management of disseminated breast cancer. AB - The management of patients with metastatic breast cancer is best achieved by the judicious use of local and systemic measures that palliate symptoms and improve overall quality of life. When two treatment approaches are known to be equally efficacious, the less toxic should be used. When disease is limited to one or two sites and the patient has an indolent form of the disease, the patient's symptoms are often best palliated with the use of surgery or radiotherapy alone. When multiple sites of disease are evident or the disease is progressing more rapidly, systemic therapy is preferred, and local therapies should be added when the patient is clearly refractory to systemic therapy or when the disease site is unlikely to be adequately palliated with systemic therapy. The use of any of these therapies, including chemotherapy, has a relatively small effect on the median survival of patients with metastatic breast cancer. However, improvements in quality of life are usually greatest with regimens inducing the highest response rates, even when these regimens are associated with greater toxicity. The characteristics of patients likely to respond to endocrine therapy are well defined; in these patients endocrine therapy should be used as the first form of systemic therapy. Among endocrine therapies, the least toxic is used first. The selection of patients for chemotherapy is largely a process of exclusion. When chemotherapy is used, there are a number of different strategies for sequencing chemotherapy that appear to be equally efficacious. In general, patients should be treated with standard doses of drug combinations for a period in excess of 3 months. When used inappropriately, especially in asymptomatic patients, these therapies may actually compromise the patient's quality of life. The use of surgery, radiation therapy, and systemic therapy should be integrated with various types of psychosupport services, especially peer support groups. Patients who want to try new forms of therapy should do so early in the course of the disease when these therapies are most likely to be effective and the patient has the least to lose if the therapy proves ineffective. This is especially true because the use of the most effective regimens at a time when the patient is asymptomatic may mean that the patient is resistant to most or all therapies of proven value when most in need of palliation. PMID- 2205377 TI - K-ras activation in neoplasms of the human female reproductive tract. AB - The role of cellular oncogenes in the development of epithelial tumors of the human female reproductive tract has not previously been extensively studied. DNAs isolated from ten human uterine, 13 ovarian, and four cervical neoplasms and from three cell lines derived from endometrial adenocarcinoma were investigated by dot blot hybridization after polymerase chain reaction amplification of ras gene sequences and in some cases by NIH 3T3 transfection. Transforming activity was found in two of nine endometrial adenocarcinomas, but none of seven ovarian carcinomas and none of four cervical carcinomas showed transforming activity. K ras sequences with a GGT----GAT mutation in codon 12 were demonstrated in both transformants derived from endometrial carcinoma. K-ras codon 12 mutations were similarly detected in six of 13 endometrial carcinomas (one GAT and GCT, one GTT and GCT, two GAT, two GTT) and two of 13 ovarian tumors (GAT and GCT, GAT), both mucinous adenocarcinomas. Point mutation of K-ras in codon 12 is thus comparably frequent in uterine endometrial carcinomas and in colorectal carcinomas and may have similar significance as an event that contributes to progression of these tumors. Cervical carcinomas and ovarian tumors in general, with the possible exception of mucinous adenocarcinoma of the ovary, do not appear to have this characteristic. PMID- 2205376 TI - Mammalian O6-alkylguanine-DNA alkyltransferase: regulation and importance in response to alkylating carcinogenic and therapeutic agents. PMID- 2205378 TI - In vitro assessment of the effects of granulocyte-macrophage colony-stimulating factor on primary human tumors and derived lines. AB - One hundred eighty-nine human tumor specimens were tested in a human tumor cloning assay to determine their growth response to human recombinant granulocyte macrophage colony-stimulating factor. Of these samples 48 were evaluable for response. Growth stimulation to greater than 150% of controls was noted in 1 of 12 lung cancers (8%) and 1 of 14 breast cancers (7%) but in no other instances for an overall rate of 2 of 48 (4.2%). A dose-response effect was not seen with each of the two stimulated samples responding only at the two lowest concentrations tested. In addition, 7 cell lines derived from human tumors were tested using a metabolic CO2 production assay without evidence of growth stimulation. Samples of normal bone marrow displayed the usual dose-dependent stimulation whether grown in agar or assayed metabolically. We conclude that human recombinant granulocyte-macrophage colony-stimulating factor has minimal effect on the growth of the solid tumors tested and that clinical trials to reduce chemotherapy-associated myelo-suppression may proceed without undue concern for enhancement of tumor growth. PMID- 2205379 TI - Phase I trial of intraperitoneal recombinant interleukin-2/lymphokine-activated killer cells in patients with ovarian cancer. AB - Ten patients with ovarian cancer refractory to conventional therapy were treated with intraperitoneal (i.p.) recombinant interleukin-2 (rIL-2) and lymphokine activated killer cells (LAK). The 28-day protocol consisted of 6 priming i.p. rIL 2 infusions on days 0, 4, 6, 8, 10, and 12. Leukapheresis was performed for mononuclear cell collection on days 15, 16, 17, and 18 and lymphokine-activated killer cells were given i.p. with the rIL-2 on days 19 and 21. Three additional i.p. rIL-2 infusions were given on days 23, 25, and 27. Three dose levels of rIL 2 were tested: 5 X 10(5), 2 X 10(6), and 8 X 10(6) units/m2 body surface area. The dose-limiting toxicity was abdominal pain secondary to ascites accumulation with significant weight gain. Other toxic effects included decreased performance status, fever, nausea and vomiting, diarrhea, and anemia. Peripheral lymphocytosis and eosinophilia were seen at all dose levels. The maximum tolerated dose is 8 X 10(6) units/m2/dose. Peripheral and peritoneal IL-2 levels were measured with a bioassay using an IL-2-dependent cell line. At the highest dose level, serum IL-2 was greater than 10 units/ml for 18 h. After the first infusion, a 2-log dilution of the i.p. IL-2 was measured in the serum. In the postleukapheresis i.p. IL-2-dosing period less IL-2 was detected in the serum than in the earlier i.p. IL-2-priming period. The induction and persistence of LAK activity were studied. Peritoneal LAK activity was detected as early as 4 days after the first i.p. infusion, by day 11 in all evaluable patients, and persisted for the 6-day interval between priming IL-2 and LAK/IL-2 infusion. Peritoneal lytic activity persisted until day 28 in 5 tested patients. These peritoneal cells retained lytic activity 48 h in culture medium without rIL-2 present. Peritoneal LAK activity correlated with the percentage of mononuclear cells and the percentage of CD56-positive mononuclear cells in the peritoneum. The yield of peripheral lymphocytes after the six i.p. priming doses of rIL-2 correlated with the dose level of rIL-2 infused. Peripheral blood LAK activity showed a minimal, however progressive, increase during the treatment protocol. LAK activity could be enhanced if rIL-2 was present during the 4-h assay. These studies indicate that i.p. rIL-2 infusion induced durable regional LAK activity and primes peripheral blood cells for LAK activity if exposed briefly to additional IL-2. PMID- 2205380 TI - Antisense inhibition of single copy N-myc expression results in decreased cell growth without reduction of c-myc protein in a neuroepithelioma cell line. AB - The N-myc gene is transiently expressed during normal embryonic development and abnormally expressed in several tumors of neuroendocrine origin. Little is known of the function of the N-myc gene product in either normal or neoplastic tissue. We utilized synthetic antisense oligodeoxynucleotides to specifically inhibit N myc gene expression in the neuroepithelioma cell line CHP100. These cells contain single copy N-myc alleles but overexpress c-myc. N-myc antisense oligomer treatment was found to be growth inhibitory without affecting levels of c-myc protein. N-myc antisense oligomer-treated cells also lost the characteristic cellular heterogeneity displayed by CHP100 in vitro. PMID- 2205381 TI - Growth adaptation to methotrexate of HT-29 human colon carcinoma cells is associated with their ability to differentiate into columnar absorptive and mucus secreting cells. AB - The purpose of this work was to investigate whether the phenomenon of metabolic adaptation of HT-29 cells to glucose deprivation and subsequent emergence of differentiated subpopulations (A. Zweibaum et al., J. Cell. Physiol., 122: 21-29, 1985) also applies to anticancer drugs that act at a metabolic level like methotrexate (MTX). Stepwise adaptation of exponentially growing HT-29 cells to increasing concentrations of MTX (10(-7), 10(-6), and 10(-5) mol) results, after a phase of high mortality, in the emergence of subpopulations with stable growth rates and curves close to those of untreated control cells. In contrast to control cells which are heterogenous and contain, after confluency, only a small proportion of differentiated cell types (less than 4%), postconfluent cultures of MTX-adapted cells are totally differentiated. Cells adapted to 10(-7) M MTX form a mixed population of columnar absorptive and mucus cells; at higher concentrations cells are almost exclusively of the mucus-secreting type. All cells, whether mucus-secreting or not, develop an apical brush border which strongly expresses dipeptidylpeptidase IV, carcinoembryonic antigen, and villin. These differentiation features, which resemble those of fetal colon, are associated with decreased rates of glucose consumption and lactic acid production. Both differentiation characteristics and metabolic changes are stably maintained when the cells are subcultured in the absence of the drug. Like the original population, MTX-adapted cells are tumorigenic in nude mice. We propose that cells which are able to differentiate and which are the origin of the small proportion of differentiated cell types found in postconfluent cultures of the original cell line possess an advantage which allows them to be adaptable to "metabolic stress" conditions. PMID- 2205382 TI - Cellular electrophysiologic mechanisms of cardiac arrhythmias. AB - Cardiac arrhythmias result from abnormalities in the initiation of impulses or in the conduction of these impulses through the heart. Arrhythmias caused by impulse initiation may be caused by either automaticity or triggered activity. Arrhythmias caused by abnormalities in conduction are often the result of reentrant excitation. These arrhythmogenic mechanism arise because of alterations in the transmembrane potentials of cardiac cells that are often caused by disease. These cellular mechanisms causing arrhythmias are the subject of this article. PMID- 2205384 TI - Noninvasive evaluation of supraventricular tachycardias. AB - In this article we discuss the role of noninvasive methods in evaluation of supraventricular tachycardias. The limitation of Holter monitoring and exercise testing is discussed. A significant portion of the article is devoted to the role of esophageal recording, body surface potential mapping, and phase image analysis, areas that are often underutilized but that have potential in the diagnosis of supraventricular tachycardias. PMID- 2205383 TI - Differential diagnosis of supraventricular tachycardia. AB - We firmly believe that a systematic approach to the 12-lead ECG can provide information that can diagnose the difference between ventricular and supraventricular tachycardia, and in many instances diagnose the mechanism and site of origin of the supraventricular tachycardia. The mechanism of supraventricular tachycardia is able to be diagnosed in more than 80% of narrow complex tachycardias, and one should be able to distinguish supraventricular from ventricular tachycardia in more than 90% of tachycardias. In the presence of aberration, the mechanism of supraventricular tachycardias is more difficult to define unless retrograde P waves are seen. In such instances the morphology of the P wave (if seen), the effect of oscillation of cycle length on the RP interval, and response to vagal maneuvers may be useful in distinguishing mechanisms for ventricular tachycardia. PMID- 2205385 TI - Invasive electrophysiologic evaluation of patients with supraventricular tachycardia. AB - This article describes the clinical and technical aspects of invasive electrophysiology studies in patients with supraventricular tachycardia. The methods and interpretation of programmed stimulation and pharmacologic interventions during sinus rhythm and supraventricular tachycardia are discussed. PMID- 2205386 TI - Clinical evaluation in therapy of patients with atrial fibrillation or flutter. AB - The weight of evidence clearly indicates that both atrial fibrillation and atrial flutter are due to a reentrant mechanism. Atrial fibrillation seems almost certainly due to multiple circulating reentrant wavelets of the leading circle type, whereas atrial flutter appears to be caused by single reentrant circuit located in the right atrium. The diagnosis of both atrial fibrillation and atrial flutter should always be possible using either old or new techniques. The interruption of atrial flutter should be possible using pacing or direct current cardioversion techniques, and the conversion of atrial fibrillation to sinus rhythm also is most often possible by direct current cardioversion or antiarrhythmic drug therapy. Long-term antiarrhythmic drug therapy to suppress recurrent atrial fibrillation and atrial flutter may be a problem, but availability of newer antiarrhythmic agents holds promise for finding an effective regimen. Catheter ablation techniques may be used to cause complete heart block in the treatment of either atrial fibrillation or atrial flutter when these rhythms cannot be satisfactorily suppressed and are associated with unacceptably rapid ventricular response rates. Finally, recent data suggest that atrial flutter may be successfully treated on a chronic basis with an antitachycardia pacing device, may be cured with catheter ablation techniques applied to a critical portion of the atrial flutter reentry circuit, and may be treated successfully with innovative surgical techniques. The latter is also true for atrial fibrillation. PMID- 2205387 TI - Clinical management of patients with atrioventricular nodal reentrant tachycardia. AB - A broad array of therapeutic options is currently available for the management of patients with AV nodal reentrant tachycardia. While acute termination of tachycardias is readily achieved, either by vagal maneuvers or intravenous medication, the decision to embark on a long-term therapeutic plan to prevent recurrences must be clinically individualized. When a chronic pharmacologic approach is desired, electrophysiologic testing is invaluable for confirming the diagnosis and selecting appropriate medication. However, the growing awareness of potential proarrhythmic effects and the inconvenience and expense of lifelong drug therapy, coupled with other advances in the field, have made nonpharmacologic approaches more attractive. This is especially so for symptomatic younger patients. The definitive cure rates achievable with surgery are now being approached by transcatheter AV nodal modification procedures that ablate AV nodal reentrant tachycardia while preserving anterograde AV nodal conduction. Over the next decade, it is likely that the latter technique will become widely used for the long-term management of symptomatic AV nodal reentrant tachycardia. PMID- 2205388 TI - Diagnosis and treatment of patients with accessory pathways. AB - Of the accessory pathways, partially or totally bypassing the atrio-ventricular conduction system, the bundle of Kent is the most common type. The electrocardiographic (ECG) expression of preexcitation depends upon the contribution of the activation fronts over the AV node and the accessory pathway. From the polarity of the delta wave in the surface ECG and from the behavior during electrophysiologic study, the location of the accessory pathway can be derived. The presence of an accessory pathway may induce circus movement tachycardia and, in case of atrial fibrillation, high ventricular rates possibly leading to sudden death. Noninvasive techniques are able to identify the patient at high risk. Treatment modalities are pharmacologic or surgical, whereas ablation techniques are still under investigation. PMID- 2205389 TI - Surgical therapy for patients with supraventricular tachycardia. AB - Surgical techniques have now been developed to treat a variety of supraventricular arrhythmias, including the Wolff-Parkinson-White syndrome, arrhythmias associated with other atrioventricular accessory connections, AV nodal reentrant tachycardia, and automatic (ectopic) atrial tachycardias. In addition, atrial flutter and atrial fibrillation are not potentially curable with surgical intervention. This article will discuss the current surgical techniques used to treat these supraventricular tachyarrhythmias. PMID- 2205390 TI - Catheter ablation of accessory pathways. AB - Catheter ablation techniques offer an alternative to surgical ablation of accessory pathways. These techniques make use of direct current countershocks, radio frequency energy, or laser energy. This article presents the experimental background and the clinical experience with these techniques. PMID- 2205391 TI - Modification of the atrioventricular node. A new approach to the treatment of supraventricular tachycardias. AB - Atrioventricular nodal modification appears to be a relatively safe and effective treatment option for patients with refractory AV nodal reentrant tachycardia. Hopefully, the long-term results will be as encouraging as the initial experience. Newer surgical and catheter techniques, together with a better understanding of the mechanisms underlying AV nodal reentrant tachycardia, may lead to improved efficacy and safety. In the future, AV nodal modification may obviate the need for drug therapy in patients with symptomatic AV nodal reentrant tachycardia and be applied to the treatment of other supraventricular tachycardias. PMID- 2205392 TI - Immunocytochemical study of pepsinogen 1-producing cells in the fundic mucosa of the stomach in developing mice. AB - Development and maturation of pepsinogen 1-producing cells were studied in the gastric fundic mucosa of the mouse by means of light- and electron-microscopic immunocytochemistry using rabbit anti-rat pepsinogen 1-serum. In the adult mouse, secretory granules in mucous neck cells, transitional mucous neck/chief cells and chief cells are immunolabeled. The numerical density of gold particles on zymogen granules is not significantly altered among different stages of maturation of chief cells. In addition, rough endoplasmic reticulum and Golgi complex of these cell types show a weak labeling. In mice from day 16 of gestation to postnatal day 14, mucous neck cells and chief cells cannot be distinguished, but only one type of pepsinogen 1-producing cell, called 'primitive chief cell', is identified in the fundic gland. The intensity of immunoreactivity of secretory granules in primitive chief cells is uniform within an individual cells but varies greatly among different cells. The majority of primitive chief cells contains weakly labeled granules regardless of the maturation stage of cells or of animals. On postnatal day 21, mucous neck, transitional and chief cells are distinguishable, and secretory granules in these cells are intensely immunolabeled as in the adult. These results suggest that pepsinogen 1-production rapidly increases with differentiation of mucous neck and chief cells. PMID- 2205393 TI - The immunocytochemical localization of angiotensinogen in the rat ovary. AB - The present study examined the presence and cellular distribution of angiotensinogen, the precursor to the angiotensin peptides, in the ovary of the normal cycling rat by immunocytochemistry. Angiotensinogen staining was present in the granulosa cells of maturing follicles and to a lesser extent in those undergoing atresia. Staining was not seen in the granulosa cells of primordial or early primary follicles. In maturing follicles intense staining for angiotensinogen was confined to the antral cell layers, cells of the cumulus oophorus and in the follicular fluid. Strong immunostaining was also seen in the germinal epithelium covering the ovary. Lighter angiotensinogen staining was observed in some parts of the cortical and medullary stroma and occasionally in corpora lutea. No variation in the intensity or pattern of angiotensinogen staining was observed throughout the estrous cycle. Comparison of the distribution of angiotensinogen with the previously described localization of renin, AII, angiotensin converting enzyme and AII receptors, suggests that there are a number of intra-ovarian sites at which AII could be produced. PMID- 2205394 TI - The role of charged amino acids in the localization of secreted and membrane proteins. PMID- 2205395 TI - Control of cell fate in a vertebrate neurogenic lineage. PMID- 2205396 TI - The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain. AB - The Wnt-1 (int-1) proto-oncogene, which encodes a putative signaling molecule, is expressed exclusively in the developing central nervous system and adult testes. To examine the role of Wnt-1, we generated six independent embryonic stem cell lines in which insertion of a neoR gene by homologous recombination inactivated a Wnt-1 allele. Germline chimeras were generated from two lines, and progeny from matings between heterozygous parents were examined. In all day 9.5 fetuses homozygous for mutated Wnt-1 alleles, most of the midbrain and some rostral metencephalon were absent. The remainder of the neural tube and all other tissues were normal. In late-gestation homozygotes, there was virtually no midbrain and no cerebellum, while the rest of the fetus was normal. Homozygotes are born, but die within 24 hr. Thus the normal role of Wnt-1 is in determination or subsequent development of a specific region of the central nervous system. PMID- 2205397 TI - A nuclear translational block imposed by the HIV-1 U3 region is relieved by the Tat-TAR interaction. AB - Replication of HIV-1 depends on the viral Tat protein, which functions via a target sequence, TAR, present in the proviral long terminal repeat (LTR) and at the 5' end of viral mRNAs. We have shown that Tat potentiates the expression of TAR-containing RNAs, but only when Tat and the TAR-containing RNA are present in the nucleus. We now show that a small change in the TAR loop abolishes nuclear potentiation by Tat. Furthermore, the HIV-1 U3 region induces expression incompetence in mRNA synthesized by this promoter. RNAs of identical structure are, however, translated efficiently when produced from the CMV-IE promoter. The Tat-TAR system appears, therefore, to rescue the expression potential of HIV-1 LTR-directed RNA. PMID- 2205399 TI - [Inflammatory intraocular complications after placement of retropupillary lenses]. AB - In 194 patients aged 32-81 years 200 retropupillary lenses were administered. 129 lenses were implanted into the sulcus ciliaris, 71 lenses into the lenticular capsule. The surgical technique was the same in both groups. The authors divide inflammatory postoperative complications they encountered into two major groups: cellular reactions on the anterior surface of the lens and fibrinoid reactions with the formation of membranes or synechiae. The authors discuss possible reasons for the development of these complications and possibilities of therapy. PMID- 2205398 TI - Distinct classes of transcriptional activating domains function by different mechanisms. AB - We have previously shown that the two transcriptional activation functions (TAF-1 and TAF-2) of the human estrogen receptor (hER) have synergistic properties different from one another and from those of acidic activating domains (AADs). Here we compare the transcriptional interference/squelching properties of the hER TAFs with those of the AADs of yeast GAL4 and chimeric GAL-VP16 activators. Our results indicate that AADs interact with a factor(s) that, while required for activation by AADs, is not essential for activation by hER TAFs. In contrast, hER TAFs appear to interact with factors indispensable for mediating both their activation function and that of AADs. Thus, different classes of trans-activators may interact with different factors. In addition, the synergistic and transcriptional interference/squelching properties of the two TAFs of the human glucocorticoid receptor (hGR) indicate that both are composed of acidic and nonacidic activation functions. PMID- 2205400 TI - [Clinical trial of Pilogel HS made by Alcon]. AB - The authors give an account on the results of clinical tests of the anti glaucomatous preparation PILOGEL HS of ALCON Co. The drug replaced in all groups of patients reliably 1-3% Pilocarpine administered three times a day, as regards its effect on intraocular tension. Its great practical advantage is that the effect is achieved after a single administration per 24 hours (at night). In particular patients in their productive age appreciate this advantage. The preparation was included in the import plan. PMID- 2205401 TI - [Din fubao and his early involvement in editing and translating medical books]. PMID- 2205402 TI - [Recent traditional Chinese medicine treatment of chronic bronchitis]. PMID- 2205403 TI - The role of 8-hydroxyguanine in carcinogenesis. PMID- 2205404 TI - Metabolic activation of 9-hydroxymethyl-10-methylanthracene and 1 hydroxymethylpyrene to electrophilic, mutagenic and tumorigenic sulfuric acid esters by rat hepatic sulfotransferase activity. AB - Our previous studies on 7-hydroxymethyl-12-methylbenz[a]anthracene and 6 hydroxymethylbenzo[a]pyrene showed that cytosolic sulfotransferase activity plays a major role in the formation of hepatic benzylic DNA and RNA adducts by these carcinogens in rats. In the present study, we found similar sulfotransferase activity in rat liver cytosol which activates 9-hydroxymethyl-10-methylanthracene (HMA) and 1-hydroxymethylpyrene (HMP) to electrophilic sulfuric acid ester metabolites. Thus, incubation of these nonbay region hydrocarbons with calf thymus DNA in the presence of liver cytosol fortified with the sulfo-group donor, 3'-phosphoadenosine-5'-phosphosulfate (PAPS) produced benzylic DNA adducts that were chromatographically identical to those obtained by the reactions of the corresponding sulfuric acid esters with deoxyguanosine and deoxyadenosine. These adducts were also produced in the livers of infant rats injected i.p. with 0.25 mumol/g body wt of HMA or HMP. Administration of comparable doses of 9 sulfooxymethyl-10-methylanthracene (SMA) and 1-sulfooxymethylpyrene (SMP) resulted in much higher levels of hepatic benzylic DNA adducts than did the parent hydroxymethyl hydrocarbons. Both HMA and HMP induced His+ revertants in Salmonella typhimurium TA98 when preincubated with these bacteria in the presence of rat liver cytosol and PAPS. This sulfotransferase-mediated mutagenicity of HMA and HMP was reduced by dehydroepiandrosterone, an inhibitor of hepatic sulfotransferase activity for these hydrocarbons. SMA and SMP were directly mutagenic and their intrinsic bacterial mutagenicity was inhibited by glutathione (GSH) and GSH-S-transferase activity. Chloride ion at physiological concentrations enhanced the bacterial mutagenicity of SMA through the formation of 9-chloromethyl-10-methylanthracene as previously observed for SMP by Henschler et al. In contrast to the higher mutagenicity of 1-chloromethylpyrene (CMP) than SMP in bacteria, CMP formed smaller amounts of hepatic benzylic DNA adducts in rats than the sulfuric acid ester. SMA and SMP were weak skin tumor initiators in the mouse, but they were more active than HMA and HMP in this regard. PMID- 2205405 TI - Detection of (3'-hydroxy)-3,N4-benzetheno-2'-deoxycytidine-3'-phosphate by 32P postlabeling of DNA reacted with p-benzoquinone. AB - Cytidine-3'-phosphate was reacted with p-benzoquinone under neutral aqueous conditions, and the fluorescent product formed was isolated and characterized. The structure of the covalent adduct was identified as (3'-hydroxy)-3,N4 benzetheno-cytidine-3'-phosphate by high-resolution MS and 1H NMR spectroscopy. A similar product was isolated from the reaction of 2'-deoxycytidine-3'-phosphate with a hydroquinone-p-benzoquinone mixture. 32P-Postlabeling of calf thymus DNA reacted with p-benzoquinone detected several adducts, the principal adduct being (3'-hydroxy)-3,N4-benzetheno-2'-deoxycytidine-3'-phosphate. Our studies demonstrate that the reaction of DNA with p-benzoquinone in vitro leads to multiple DNA adducts. 32P-Postlabeling may allow detection of benzene-DNA adducts in vivo. PMID- 2205406 TI - Stimulation of DNA synthesis in carcinogen-induced diploid hepatocytes in vitro. AB - Diploid hepatocytes induced by a combination of diethylnitrosamine and 2 acetylaminofluorene were isolated and separated from polyploid hepatocytes by centrifugal elutriation. The diploid and polyploid cell fractions were approximately 90% pure and contained between 1 and 1.5 x 10(7) cells. When kept in monolayer cultures both cell populations responded to the mitogenic effect of EGF and insulin. However, the percentage of labelled nuclei was higher in predominantly diploid compared to predominantly tetraploid hepatocyte cultures at all epidermal growth factor (EGF) concentrations used in this study. At 10 ng EGF/ml and 10 mU insulin/ml the labelling index was twice as high in the diploid liver cells. Further work is required to show the relevance of the stronger response of the diploid cell fraction to mitogens in the process of carcinogenesis. PMID- 2205407 TI - Genotoxicity of methylglyoxal: cytogenetic damage in human lymphocytes in vitro and in intestinal cells of mice. AB - The mutagenic activity of methylglyoxal (MG) was assayed in vitro in human lymphocytes [induction of chromosomal aberrations (CAs), sister chromatid exchanges (SCEs) and micronuclei] both in the presence and in the absence of metabolic activation (S9 mix). The Ames/microsome test was performed with the Salmonella typhimurium strains considered more responsive (TA102 and TA104). Positive results were obtained for all the genetic endpoints analysed. In human lymphocytes the activity of MG is decreased by the presence of S9 mix. In the in vivo studies, the metaphase analysis in the ileum and duodenum cells of mice treated per os with MG (400 and 600 mg/kg body wt) gave negative results for CA induction, while only a weak increase of SCE in duodenum cells at the higher dose was obtained. Dimethylhydrazine (25 mg/kg body wt), as positive control, was clearly active in inducing both CAs and SCEs in the same intestinal tissues. PMID- 2205408 TI - Intestinal first-pass metabolism of nitrosamines. 4. Metabolism of N nitrosodibutylamine in vascularly autoperfused jejunal and ileal loops of rats. AB - N-Nitrosodi-[1-14C]butylamine (NDBA) has been shown to undergo a high first-pass metabolism in isolated perfused rat small intestinal segments. Metabolites resulting from omega-hydroxylation of NDBA, the bladder carcinogens N nitrosobutyl-(4-hydroxybutyl)amine (NB4HBA) and N-nitrosobutyl-(3-carboxypropyl) amine (NB3CPA), accounted for greater than 90% of the total radioactivity absorbed. In the present study using vascularly perfused rat small intestinal segments, the high first-pass metabolism of NDBA could be confirmed under near in vivo conditions despite the much higher absorption rate. At the end of the 36 min experimental period 70-80% of the dose have been absorbed via the portal blood as opposed to 1-10% of the dose after 2 h in vitro perfusion. omega-Hydroxylation was again the most important metabolic pathway. However, the relationship of NB3CPA to NB4HBA was shifted in favor of NB4HBA, indicating a concentration and absorption rate dependency in the further metabolism of NB4HBA to NB3CPA. PMID- 2205409 TI - The metabolism of 1-nitropyrene by human cytochromes P450. AB - The metabolism of [3H]1-nitropyrene by specific forms of human cytochrome P450 was investigated in vitro using Vaccinia virus expression of P450 cDNAs in HepG2 cells. Cell lysates were injected individually with recombinant Vaccinia virus containing human P450 cDNA (P450 IA2, IIA3, IIB7, IIC8, IIC9, IID6, IIE1, IIF1, IIIA3, IIIA4, IIIA5 AND IVB1). Only IIIA3 and IIIA4 demonstrated significant activity in the C-oxidation of 1-nitropyrene. The principal metabolite from both P450 forms was 1-nitropyren-3-ol, produced in at least 4-fold greater abundance than the mixture of 1-nitropyren-6-ol and 1-nitropyren-8-ol, or the K-region dihydrodiols. This is in contrast to the metabolism in many species where 6-ol and 8-ol formation predominate over 3-ol formation. In fact, in rats and rabbits, P450 forms quite distinct from the IIIA P450s catalyze the majority of the metabolism of this pollutant. This is the first demonstration of the role of individual human P450 forms in the metabolism of a representative chemical in this important class of environmental pollutants. The importance of these observations in the overall carcinogenic risk of humans to these chemicals remains to be established. These studies furthermore establish a marked species difference in the metabolism of nitrated polycyclic aromatic hydrocarbons. PMID- 2205410 TI - Effect of chemical carcinogens on cholesterol biosynthetic pathways in the skin of mice. AB - The metabolism of zymosterol and mevalonic acid was studied in vitro using the skin homogenates of 3-methylcholanthrene (3MC), diazacholesterol-treated and untreated mice. In normal mouse skin only lathosterol was a major metabolite and the other metabolites, cholesta-5,7,24-trien-3 beta-ol, desmosterol, cholesterol and 7-dehydrocholesterol were much less abundant. However, in the skin homogenate of mice treated with 3MC lathosterol production was depressed, while the production of cholesta-5,7,24-trien-3 beta-ol and desmosterol was significantly increased, the cholesterol level being normal or a little higher. In contrast, in the skin homogenate of mice administered diazacholesterol the production of both lathosterol and cholesterol was almost completely blocked with the slightly increased production of cholesta-5,7,24-trien-3 beta-ol and desmosterol. The metabolism in vitro of [2-14C]-mevalonic acid was quite similar to that of zymosterol, and no additional product which might possibly have been produced by the Kandutsch-Russell pathway was observed. Two pathways for cholesterol biosynthesis, therefore, may exist in mouse skin; the first is lanosterol--- zymosterol----5 alpha-cholesta-7,24-dien-3 beta-ol----lathosterol----7 dehydrocholesterol----cholesterol, and the second by Bloch: lanosterol--- zymosterol----5 alpha-cholesta-7,24-dien-3 beta-ol----cholesta-5,7,24-trien-3 beta-ol----desmosterol----cholesterol. When mouse skin is treated with 3-MC the former pathway is virtually blocked and the latter is stimulated, keeping the level of cholesterol in the tissue constant or a little higher than normal, which seems to be a significant change in the early stage of chemical carcinogenesis. PMID- 2205412 TI - Rate-modulated pacing. AB - The primary role of cardiac rate in adapting cardiac output to changing physiological needs has been more clearly recognized in recent years. Previously, the rate of cardiac stimulation had been determined either at pacemaker manufacture, by programming a single rate, or by sensing the atrium. More recently, sensing another physiological or nonphysiological function that changes in response to body need has become possible. Exercise changes blood oxygen saturation, central venous pH, central venous temperature, minute ventilation and respiratory rate, stroke volume, circulating catecholamines, QT interval, evoked endocardial response to a stimulus, and the mechanics of myocardial contraction. Some sensors respond to muscle work but not to intellectual effort or emotion. Pacemaker-based sensors of physiological function or activity allow a change in cardiac stimulation rate in response to need. Whichever sensor is used, increases in ventricular rate during exercise regularly produce a cardiac output response. Single-chamber, rate-modulated pacemakers in atrium or ventricle and dual-chamber devices are now implanted on a widespread basis. These drive the atrium, the ventricle, or both, sensing or pacing the atrium at a rate determined by the sensor. PMID- 2205411 TI - Effect of nicotine and tobacco-specific nitrosamines on the metabolism of N' nitrosonornicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone by rat oral tissue. AB - The effect of N'-nitrosoanatabine (NAT) and nicotine on the metabolism of N' nitrosonornicotine (NNN) and 4-(methyl-nitrosamino)-1-(3- pyridyl)-1-butanone (NNK) by cultured rat oral tissue was investigated. The effect of NNN on NNK metabolism and the effect of NNK on NNN metabolism was also determined. NNK inhibited NNN metabolism more than NNN inhibited NNK metabolism. NAT inhibited the metabolism of NNK but not of NNN. Nicotine, which is present at greater than 500 times the levels of NNN and NNK in smokeless tobacco, inhibited the metabolism of both nitrosamines. Inhibition of 1 microM NNN metabolism was greater than that of 1 microM NNK when the concentration of nicotine was 1, 10 or 100 microM. Nicotine at 100 microM inhibited the formation of all metabolites of NNN by 85-92%. These results suggest that NNN and nicotine may be metabolized by a common enzyme. PMID- 2205413 TI - Influence of myocardial ischemia and infarction on autonomic innervation of heart. PMID- 2205414 TI - Recurrent pericarditis. Relief with colchicine. AB - Recurrence is one of the major complications of pericarditis. Treatment of recurrence is often difficult, and immunosuppressive drugs or surgery may be necessary. We conducted an open-label prospective study of nine patients (seven men and two women; age, 18-64 years; mean age, 41.7 +/- 13.7 years). Patients were treated with colchicine (1 mg/day) to prevent recurrences. All patients had suffered at least three relapses despite treatment with acetylsalicylic acid, indomethacin, prednisone, or a combination. Pericarditis was classified as idiopathic in five patients, postpericardiotomy in two, post-myocardial infarction in one, and associated with disseminated lupus erythematosus in one. For statistical analysis, we conducted a paired comparison design (Student's t test). All patients treated with colchicine responded favorably to therapy. Prednisone was discontinued in all patients after 2-6 weeks (mean, 26.33 +/- 10.9 days), and colchicine alone was continued. After a mean follow-up of 24.3 months (minimum, 10 months; maximum, 54 months), no recurrences were observed in any patient; there was a significant difference between the symptom-free periods before and after treatment with colchicine (p less than 0.002). Our study suggests that colchicine may be useful in avoiding recurrence of pericarditis, although these results need to be confirmed in a larger, double-blind study. PMID- 2205415 TI - Assessment of mitral regurgitation by biplane transesophageal color Doppler flow mapping. AB - To test the role of recently developed biplane transesophageal color Doppler echocardiography in the assessment of severity of mitral regurgitation, we examined 51 patients undergoing cardiac catheterization and left ventriculography. Transesophageal color Doppler flow imaging detected mitral regurgitation in all 32 patients proved to have this lesion. In 10 of 16 patients without mitral regurgitation by angiography, mitral regurgitation signals were detected by transesophageal color Doppler flow imaging. Thus, the sensitivity and specificity of transesophageal color Doppler echocardiography for the detection of mitral regurgitation were 100% and 38%, respectively. There was some correlation between the regurgitant jet area from the longitudinal plane and angiographic grading. An improved angiographic correlation was achieved with the regurgitant jet area from the transverse plane. The best correlation with angiography was obtained when the maximum regurgitant jet area from two planes (the greater of the two measurements, each from a different plane) was considered. There was a significant difference in the maximum regurgitant jet area between none and mild (p less than 0.01), mild and moderate (p less than 0.001), and moderate and severe (p less than 0.01) mitral regurgitation. The maximum regurgitant jet area of less than 1.5 cm2 predicted the angiographic grading as none with a sensitivity and specificity of 88% and 94%, respectively. The maximum regurgitant jet of between 1.5 and 4 cm2 predicted the angiographic grading as mild with a sensitivity and specificity of 82% and 95%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2205416 TI - Evaluation of the associations between carotid artery atherosclerosis and coronary artery stenosis. A case-control study. AB - To evaluate the consistency, strength, and independence of the relation of carotid atherosclerosis to coronary atherosclerosis, we quantified coronary artery disease risk factors and extent of carotid atherosclerosis (B-mode score) in 343 coronary artery disease patients and 167 disease-free control patients. In univariable analyses, there was a strong association between coronary status and extent of carotid artery disease in men and women older than and younger than 50 years (p less than 0.001 for men and women greater than 50 years, p less than 0.001 for women less than or equal to 50 years, p = 0.045 for men less than or equal to 50). The relation remained strong after control for age in men and women older than 50 years and in women younger than 50 (p less than 0.001 for men and women greater than 50 years, p = 0.003 for women less than or equal to 50) but did not persist after control for age in men younger than 50. Logistic models that included coronary disease risk factors, with or without B-mode score, as independent variables and presence or absence of coronary disease as the outcome variable indicated that the extent of carotid atherosclerosis was a strong, statistically significant independent variable in models for men and women older than 50 years of age. Next, we examined the usefulness of B-mode score as an aid in screening for coronary artery disease in men and women older than 50 years. Classification rules, both including and excluding B-mode score, were developed based on logistic regression and, for comparison, recursive partitioning (decision trees). The performance of these rules and the bias of their performance statistics were estimated. The improved classification of the study sample when B-mode score was incorporated in the rule was statistically significant only for men (p = 0.015). However, the addition of B-mode score was found to 1) increase the median discrimination score for both sex groups based on the logistic model, and 2) yield better sensitivities and specificities for rules based on recursive partitioning. Thus B-mode score is strongly, consistently, and independently associated with coronary artery disease in patients older than 50 and is at least as useful as well-known risk factors for identifying patients with coronary artery disease. PMID- 2205417 TI - Relation between steady-state force and intracellular [Ca2+] in intact human myocardium. Index of myofibrillar responsiveness to Ca2+. AB - A novel approach was developed allowing the measurement of steady-state force and intracellular calcium concentration ([Ca2+]i) in tetanized human ventricular trabeculae carneae without pharmacological intervention. We compared and contrasted three methods of assessing calcium sensitivity of the myofilaments: 1) force-[Ca2+] relations in skinned fiber preparations, 2) peak twitch force-peak [Ca2+]i relations, and 3) steady-state force-[Ca2+]i relations in intact muscles. Steady-state contractile activation was achieved rapidly by tetanizing intact human trabeculae, loaded with aequorin, a Ca2(+)-sensitive bioluminescent protein, at a stimulation frequency of 15-20 Hz. Steady-state force and [Ca2+]i were measured during tetani, and the force versus [Ca2+]i relation was obtained by varying the extracellular calcium concentration ([Ca2+]o). Force-[Ca2+]i relations obtained from control and myopathic hearts were fitted to the Hill equation: %Force = [Ca2+]inh/([Ca2+]inh50% + [Ca2+]inh), where nh is the Hill coefficient, and [Ca2+]50% is the [Ca2+] required for 50% activation. The curves of tetani had Hill coefficients of 5.21 +/- 0.20 (n = 6) and 5.61 +/- 0.60 (n = 10) and [Ca2+]50% of 0.56 +/- 0.05 microM (n = 6) and 0.54 +/- 0.09 microM (n = 10) in control and myopathic muscles, respectively. We also constructed peak force-peak [Ca2+]i relations using isometric twitches from the same muscles. These curves were shifted toward higher [Ca2+]i compared with the steady-state force-[Ca2+]i curve derived from tetani. Ryanodine (1 microM), which increased the time course of the Ca2+ and force transients, shifted the peak force-peak [Ca2+]i relation to the left, without affecting the steady-state force-[Ca2+]i relation. Exposure to 10 mM caffeine shifted the steady-state force-[Ca2+]i relation to the left, whereas exposure to 3 microM isoproterenol shifted this relation to the right. Experiments using skinned fiber preparations were performed in parallel with experiments on intact muscles from the same hearts. The force-pCa (-log[Ca2+]) relations in saponin-skinned trabeculae from control and myopathic tissue were superimposable. Ryanodine (1 microM) had no effect on the force-pCa relation in skinned fibers. Maximal tension was evoked by the posttetanic twitch, which was larger than the tetanus. This potentiation was abolished in the presence of ryanodine, a sarcoplasmic reticulum inhibitor. We propose that the changes in the steady-state force-[Ca2+]i relations are correlated with alterations in the sensitivity of the myofilaments to Ca2+, whereas changes in the peak force-peak [Ca2+]i relations represent temporal changes in the twitch transient.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2205418 TI - Incidence and prognosis of secondary ventricular fibrillation in acute myocardial infarction. Evidence for a protective effect of thrombolytic therapy. GISSI Investigators. AB - The multicenter randomized study of the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico has provided the opportunity to analyze the impact of thrombolytic treatment on secondary ventricular fibrillation incidence in a large population of patients (11,712) with acute myocardial infarction. A reduction of about 20% in the frequency of secondary ventricular fibrillation was observed among patients allocated to thrombolytic treatment (streptokinase, 2.4% versus control, 2.9%; relative risk, 0.80; 95% confidence interval, 0.64-1.00). Streptokinase appeared to exert its protective effect specifically in patients treated within 3 hours of onset of symptoms (streptokinase, 2.6% versus control, 3.7%; relative risk, 0.71; 95% confidence interval, 0.53-0.95). This protection was essentially due to a reduced incidence of late ventricular fibrillation occurring after the first day of hospitalization. The 311 patients with secondary ventricular fibrillation represented an overall incidence of 2.7%. Such incidence was not related to infarct location or sex but was significantly more common in patients older than 65 years (3.3% versus 2.3% in younger patients). A significant excess of in hospital deaths was found in patients with secondary ventricular fibrillation compared with those in the reference group (38% versus 24%; relative risk, 1.98; 95% confidence interval, 1.56-2.52). Conversely, secondary ventricular fibrillation was not a predictor of 1-year mortality for hospital survivors. Thrombolytic treatment with intravenous streptokinase affords protection against secondary ventricular fibrillation most probably by a limitation of infarct size. When the arrhythmia complicates the course of infarction, it is associated with an adverse short-term outcome, whereas the long-term prognosis is not influenced. PMID- 2205419 TI - Characterization of regional diastolic pressure gradients in the right ventricle. AB - Regional intraventricular pressure gradients exist in the left ventricle (LV) during both the early and late filling phases of diastole. These regional pressure gradients comprise a fundamental component of the mechanism of normal LV filling. To determine whether similar diastolic pressure gradients also occur in the right ventricle (RV), we measured right atrial (RA) and RV regional pressures with use of micromanometers in six anesthetized, closed-chest dogs. Tricuspid flow velocity was recorded with use of transesophageal Doppler echocardiography, and right ventriculograms were obtained with contrast angiography. As in the LV, the maximum RA-RV pressure gradient during early diastole was consistently greater if RV pressure was measured near the apex than in the inflow tract (1.6 +/- 0.5 versus 0.8 +/- 0.4 mm Hg). The area of reversed pressure was also found to be significantly greater in the apex than in the inflow tract (72 +/- 43 versus 8 +/- 6 mm Hg.msec). However, unlike the LV, the lowest minimum pressure was usually recorded in the RV outflow tract, resulting in a significantly increased RA-RV outflow tract pressure gradient compared with the RA-RV apex pressure gradient (2.5 +/- 0.8 versus 1.6 +/- 0.5 mm Hg). Analysis of right ventriculograms indicates marked narrowing of the RV outflow tract at end systole in all six animals, suggesting that an end-systolic deformation in this region is the likely mechanism for production of low early diastolic pressure in this region. During atrial contraction the RV regional pressure gradient pattern was similar to the LV pattern: the RV a-wave ascent occurred earlier in the inflow tract and later in the apex. A-wave ascent appeared to occur almost simultaneously in the apex and outflow tract. In the six animals, Doppler-derived peak tricuspid flow velocity during early diastole was 35 +/- 6 cm/sec. Early tricuspid flow acceleration (393 +/- 101 cm/sec2) was found to be significantly greater than deceleration of flow (182 +/- 59 cm/sec2). Comparison of tricuspid pressure-flow data with mitral pressure-flow data previously obtained in our laboratory indicates that the driving pressure gradient across the tricuspid valve is significantly less than across the mitral. This pressure difference corresponds to differences in acceleration and peak flow found across the two valves. Consideration of these physiological patterns of RV diastolic intraventricular pressure and their relation to filling has important implications with regard to the development of indexes that characterize diastolic pressure-flow relations and provides physiological insight relating to the location of ventricular restoring forces. PMID- 2205420 TI - Optimizing thrombolytic therapy of acute myocardial infarction. PMID- 2205421 TI - Angiographic measurement of coronary blood flow reserve. Does it work? PMID- 2205422 TI - Long QT interval syndrome. A new look at an old electrocardiographic measurement- the power of the computer. AB - Because clinical studies frequently include only a marginal number of patients, these relatively new, robust statistical techniques will have increased use. The utilization of ROC curves will be more commonplace because they permit the comprehension of the data in a more dynamic mode than merely the reporting of sensitivities and specificities. PMID- 2205424 TI - Inappropriately elevated plasma insulin-like growth factor II in relation to suppressed insulin-like growth factor I in the diagnosis of non-islet cell tumour hypoglycaemia. AB - The diagnosis of non-islet cell tumour (hypoinsulinaemic) hypoglycamia has been complicated by contradictory biochemical evidence. Although insulin-like growth factor II (IGF-II) has been identified as the hypoglycaemic agent, plasma levels are often not elevated. In this study specific radioimmunoassay procedures for the measurement of IGF-I and IGF-II are described. Reference data on plasma IGF II concentrations in relation to a wide range of IGF-I levels have been accumulated using plasma samples from acromegalic, hypopituitary and insulinoma (i.e. hyperinsulinaemic hypoglycaemia) patients as well as normal subjects from all age groups. The reference data indicate that a low plasma IGF-I value is normally associated with a relatively low plasma IGF-II level. Within a group of hypoinsulinaemic hypoglycaemia patients, a small number, invariably with evidence of a neoplasm, had low plasma IGF-I concentrations but apparently normal IGF-II levels. We propose that, in such cases, an apparently normal plasma IGF-II value is inappropriately high for the low plasma IGF-I level and, in association with non-ketotic hypoinsulinaemia and suppressed plasma growth hormone (GH), is diagnostic of a non-islet cell tumour as the cause of hypoglycaemia. PMID- 2205423 TI - The independent effects of hyperandrogenaemia, hyperinsulinaemia, and obesity on lipid and lipoprotein profiles in women. AB - We performed this study to clarify the independent effects of hyperandrogenaemia, hyperinsulinaemia, and obesity on lipid and lipoprotein levels in women with hyperandrogenaemia (HA) and anovulation which we designated as the polycystic ovary syndrome (PCO). We examined fasting lipid, lipoprotein, sex hormone and insulin levels in 38 women (21 obese (ob), 17 non-obese (nob] with HA and anovulation (PCO) and 38 normal ovulatory women (21 obese, 17 non-obese), matched for age and weight. The women with PCO had significantly increased androgen levels compared to the normal women. However, total oestradiol levels were similar in the PCO and normal women. Mean fasting insulin levels and 2-h glucose levels (both P less than 0.001) were significantly higher in ob PCO women. There were significant decreases (P less than or equal to 0.01) in high-density lipoprotein (HDL) levels in both the obese groups (ob PCO and ob normal) compared to the non-obese (nob PCO and nob normal) groups. Otherwise, mean lipid and lipoprotein levels did not differ in the ob or the nob PCO women compared to the control groups. The correlations between sex hormone, lipid and lipoprotein levels differed in the four groups of women. After statistical adjustment for potential hormonal interactions, nob PCO women had significant positive correlations between testosterone and LDL levels (R = 0.51, P less than 0.05) and insulin and TTG levels (R = 0.61, P less than 0.01). Ob normal women had a significant positive correlation between oestrone and TTG levels (R = 0.44, P less than or equal to 0.05). We conclude that (1) PCO women are in a low to risk for CVD primarily because of the increased prevalence of obesity rather than the reproductive hormone abnormalities associated with this disorder. However, by their lipid profiles, the PCO women were still in a low to intermediate risk group for CVD. PMID- 2205425 TI - Enzyme immunoassay for methionine-enkephalin sulfoxide. AB - 1. An immunoassay technique employing an enzyme-labelled ligand was developed for the sulfoxide derivative of the opioid peptide methionine-enkephalin (MOE). 2. The sensitivity of the enzyme immunoassay (EIA) was approximately twofold higher than that achieved in the radio-immunoassay (RIA) using tritiated ligand. Cross reactivities of leucine-enkephalin and beta-endorphin with the EIA were less than 0.1%, while that with Gly-Gly-Phe-Met and oxidized Gly-Gly-Phe-Met were 2.5% and 10.2%, respectively. 3. These results indicate that the EIA is a useful alternative to the RIA for the assay of small peptides. PMID- 2205426 TI - Multiple pregnancy. AB - Most multiple pregnancies are diagnosed, but early diagnosis still presents some problems. Congenital malformation is commoner in multiple pregnancies, usually without concordance, which complicates decisions about pregnancy termination. Because of the higher perinatal mortality rates, women with multiple pregnancies should be offered extra antenatal care, with the specific objectives of early diagnosis and timely treatment of pre-eclampsia, preterm labour and growth retardation. If growth retardation affects only one fetus, intervention must be carefully judged. Measures such as bedrest, fetal monitoring and elective operative delivery are reviewed, and no evidence of benefit is found from their routine use. However, such interventions are valuable in selected cases. PMID- 2205427 TI - Medical complications in pregnancy. PMID- 2205428 TI - Social problems. AB - It has long been established that social deprivation adversely affects health, including that of the pregnant woman and her baby; it is therefore justifiable to use medical resources in the treatment of social problems. Antenatal inpatient care was originally seen as potentially beneficial for women without major medical problems, but such a philosophy is not reflected in current practice. Current antenatal outpatient services do not address the needs of women with social problems who, viewing such services as hostile, may fail to attend. Special services such as help with drugs problems or HIV counselling or screening may be rejected from fear of prejudice and consequent repercussions. Such prejudice often arises because staff do not fully understand the issues involved. Antenatal care for women with social problems should consider women in the context of their families and social environment and should be provided by a small number of familiar staff forming part of an integrated multidisciplinary team in close and regular contact. Antenatal admission, if it is the woman's wish, should be viewed as justified in the management of social problems; conversely, women should not be pressurized into admission or made to feel guilty if unable to comply. Outpatient antenatal services should be conveniently sited in the community close to other relevant services and should be flexible, not only in terms of organization and format, but also in the roles of the participants. They should be comprehensive, but with special services in addition to, not instead of, routine care, and provided by a team of appropriately trained staff. In the provision of antenatal care for women with social needs, no single format will be universally applicable or desirable, and the precise design and content of the service should be variable according to local requirements and should take account of the women's wishes as well as their needs. Ultimately it will only be if the women perceive the service as being in their interests and as meeting their needs that they will use it; only if they choose to use it, will it have any chance of success. PMID- 2205430 TI - Variations in provision and uptake of antenatal care. AB - Antenatal care providers vary from one country to another. In Europe, most of the care is provided by obstetricians in some countries, while the role of midwives is important in other countries. Many women are attended by general practitioners in Canada and, to a lesser extent, in the US. Involvement of traditional birth attendants in antenatal care in more than 5% of the pregnancies has been reported in Guatemala, Honduras and Mexico only. Several indicators may be used to measure the utilization of antenatal care: the percentage of women receiving care, timing of the first visit, proportion of women receiving late or no care, number of visits and indexes of adequacy of antenatal care. Recent world data are provided. The percentage of women receiving antenatal care is higher than 90% in many countries, including some developing countries. However, the proportion of women with late or no care is increasing in the US. Women of low sociodemographic status are at high risk of having inadequate care. Financial barriers play a major role. Inadequate system capacity, distance, long waiting time, lack of child care and differences in culture, attitude and knowledge are other important barriers. Improving the services and outreach of non-participating women may both increase the utilization of antenatal care. Overutilization should also be a matter of concern. It could be better addressed by decreasing the recommended number of visits than by requesting payment of a part of the costs by the users. PMID- 2205429 TI - Antenatal care in developing countries. AB - The problem of antenatal care in developing countries may be considered from two aspects: (a) areas where antenatal facilities are absent or are inadequate, and (b) areas where antenatal facilities are adequate but for some reasons are not adequately utilized. The solution to the first part of the problem would appear to be simple. The governments concerned should provide the required facilities. This obviously is not an easy task in many areas of the world, especially with the present profound economic depression in many developing countries. The people just have to use the facilities available to their best advantage, or do without the facilities. The second part of the problem presents more difficulties. Where antenatal facilities are available, inadequate utilization has been shown to be due to a number of factors: 1. The facilities are too distant or too expensive. It has been shown how the Nigerian authorities dealt with this problem in the Ibarapa district. However, it is a very expensive solution and few governments will be able to afford this. 2. Illiteracy or ignorance. The obvious solution to this difficulty is to educate the masses and a few governments have already embarked on these commendable programmes. Unfortunately, this procedure is expensive, may take a long time and, as already pointed out, even literate women may not use the antenatal services. 3. Traditional and cultural beliefs and prejudices. It has already been shown that this factor is a very important one in the population in developing countries, even among literate patients. The saying that 'old habits die hard' is probably apt here. Probably, with time, education and closer contact with the developed world, these prejudices will disappear. From the above observations, it would appear that an inexpensive short-term solution to the two parts of the problem mentioned above is for governments to train and use the TBAs who are already 'in our midst' and who already enjoy the confidence of the masses. The authorities, however, have to be very careful in integrating the TBAs into the health system. It has to be done very judiciously and tactfully, otherwise antagonism and unhealthy rivalry will be created between the TBAs and other members of the health team. They must be made to realize that they are a part of the health team. PMID- 2205431 TI - Routine testing and prophylaxis. AB - Routine testing and prophylaxis is considered in terms of haematological disorders, biochemical testing, hormonal testing, screening for gestational diabetes and nutritional deficiencies. Within these headings the place of routine supplementation of pregnant women with iron, vitamins, trace elements and an increased protein/calorie intake is discussed. Screening for haemoglobinopathies, irregular blood group antibodies and gestational diabetes is dealt with in detail. The place for routine prophylaxis with anti-D is considered. Biochemical and hormonal testing is covered with particular reference to the use of biochemical and hormonal assays as placental function tests and their use in assessing fetal well-being. In this respect the use of biochemical and hormonal tests to screen a pregnant population for intrauterine growth retardation is also discussed. PMID- 2205432 TI - Routine or selective ultrasound scanning. PMID- 2205433 TI - [A case of rigid spine syndrome with rimmed vacuole]. AB - A case of rigid spine syndrome associated with rimmed vacuoles in muscle biopsy is reported. A 36-year-old man was admitted to our hospital because of gait disturbance and limited mortality of the spine. His family was free from any neuromuscular disorders. He was born in normal pregnancy and delivery. His physical development was normal. At age 7, he was unable to run fast. At age 36, he had right hemiparesis and dysarthria. He was diagnosed as cerebral infarction of the left basal ganglia by brain CT. Neurological examination revealed moderate proximal dominant muscular atrophy and weakness. His spine was straight, showing loss of physiological cervical and lumbar lordosis. The neck flexion was limited but the extension was full. And he had contracture of bilateral ankle joint. Laboratory findings were all normal. The electrocardiogram showed negative T wave in V4, V5 and QT interval elongation. The echocardiogram showed diffuse decrease of ventricular wall motion. Respiratory function test revealed decrease of vital capacity. Arterial blood gases on room air showed that the PaO2 and PaCO2 were 70 mmHg and 49 mmHg, respectively. The findings of electromyogram were compatible with myopathic change. Biopsy specimen of the biceps brachii muscle showed marked variation in fiber size, type 1 fiber predominancy and atrophy, and type 2B fiber deficiency. Numerous rimmed vaculoes were found in the same muscle. Four cases of the rigid spine syndrome with rimmed vacuoles have been described. Among them, three patients died in young ages and two suffered from constrictive respiratory failure. In rigid spine syndrome with rimmed vacuole formation, the cardiac and respiratory problems must be taken account intensively. PMID- 2205434 TI - [A case of glycogen storage myopathy with acute heart failure]. AB - A case of 25-year-old woman with glycogen storage myopathy is reported here. She was hospitalized for acute heart failure after alcohol drinking. The electrocardiogram on admission showed marked ST elevation. Laboratory data showed elevated levels of serum myogenic enzymes but no rise in cardiomyogenic enzyme: CK 3862 IU/l CK-MB 35 IU/l, LDH 427 IU/l, GOT 203 IU/l. After several days, she recovered from acute heart failure and could walk without supporting. ST elevation in ECG and elevated myogenic enzymes were also normalized. The occurrence of acute myocardial infarction was ruled out because a coronary angiogram and 99 Tcm scintigram were normal. Physical examination revealed proximal muscular weakness and mental retardation (WAIS, total 72). Venous lactate response was normal after semi-ischemic forearm exercise. PAS staining of muscle specimen showed an excess deposit of glycogen. Ragged-red fibers were not seen on Gomori-trichrome stain. By electron microscopy, a large amount of glycogen particles were demonstrated in the subsarcolemma, but there were no abnormal mitochondrial changes. Biochemical analysis showed accumulation of glycogen in muscles: 28.7 mg/g muscle (normal 11.4 +/- 4.2 mg/g muscle). The activities of enzyme in the pathway of glycogen and glycogenosis (alpha glucosidase, amylo-1,6-glucosidase, phosphorylase a, phosphorylase kinase, phosphofructokinase, etc.) were within normal limits. The spectrum of glycogen iodine complex was normal. Our case was different from any type of muscle glycogen storage disease previously reported. The etiology of an excess of glycogen deposit in muscles is unknown. PMID- 2205436 TI - Definitions in chronic obstructive pulmonary disease. AB - States of airflow obstruction are common disorders which span the spectrum from asthmatic-chronic bronchitis to emphysema. Asthmatic and chronic bronchitic states are at least potentially reversible by systematic, pharmacologically oriented therapy focusing on bronchodilators and corticosteroids. Both asthmatic bronchitis, particularly when it is not adequately treated, and emphysema result in the final common pathway of COPD. These are generally progressive states, unless smoking cessation can be achieved in early or mild stages of disease. The future focuses on the great challenge of early identification, classification, and intervention. Thus, all patients with cough, dyspnea, and wheeze should be carefully evaluated by health workers who understand the history, physical examination, and simple pulmonary function tests in the context of chest radiology. These clinical methods together can help define the disease states characterized by airflow obstruction. Often, a final definition of disease cannot be made until aggressive attempts at the treatment of the airflow obstruction and its attendant symptoms complex have been vigorously pursued by experienced clinicians. PMID- 2205435 TI - [Brainstem infarcts presented medial longitudinal fasciculus (MLF) syndrome and cerebellar ataxia--report of three cases]. AB - Vascular disorders of the brainstem manifest characteristic neurologic symptoms according to their localization. The medial longitudinal fasciculus (MLF) lies in the paramedian portion of the upper brainstem tegmentum, and the lesion in this fasciculus shows specific abnormality of the eye movement pattern which is known as the MLF syndrome. Although the MLF syndrome was reported frequently to be accompanied by varieties of other neurologic deficits according to the lesion extending into the adjacent structures in the brainstem, the combination of MLF syndrome and cerebellar ataxia has attracted less attention of neurologists. Recently we experienced three cases of cerebellar ataxia arisen simultaneously with MLF syndrome. Magnetic resonance imaging (MRI) tomography or X-ray computed tomography visualized lacunar lesion(s) in the upper brainstem tegmentum in all of three cases. It was obvious that the lesion included the MLF and caused the MLF syndrome in these cases. It was speculated that ventro-caudal extension of the lesion involved the decussation of the superior cerebellar peduncle, and was responsible for the association of cerebellar ataxia with MLF syndrome. According to the recent discussion about the feeding arteries in the brainstem, we decided that the damage of the paramedian branches diverging from the basilar tip resulted in the lacunar lesion(s). The development of diagnostic procedures especially MRI enables the diagnosis of the vascular disorders in the brainstem with considerable accuracy. PMID- 2205437 TI - Epidemiology of chronic obstructive pulmonary disease. AB - Morbidity and mortality rates for chronic obstructive pulmonary disease (COPD) have been increasing over time. Epidemiologic investigators of COPD have been exploring the reasons for these increases through prevalence surveys and longitudinal studies. This article examines some of the recent findings. PMID- 2205438 TI - Pathophysiology of chronic obstructive pulmonary disease. AB - Chronic airflow obstruction (CAO) is a syndrome that is produced by a variety of lesions which may occur in bronchi (large airways), bronchioles (small airways), and lung parenchyma (gas exchanging lung). These lesions frequently occur together in various combinations because of a common etiologic agent, tobacco smoke. Occasionally, one lesion or another may play a dominant role. The major disease of the large airways is chronic bronchitis, or chronic sputum production, and it is defined clinically. Its morphologic counterpart is mucous gland enlargement. Mucous gland enlargement is poorly related to CAO. Other lesions of the large airways--inflammation, smooth muscle hyperplasia, cartilage atrophy, and bronchial wall thickening--have also been described, but their functional consequences are uncertain. Bronchiolar lesions are well recognized in CAO, but their relative importance may differ in patients with mild CAO, compared to patients with severe CAO. In mild CAO, inflammation is a very important lesion, and its probable consequences--narrowing, fibrosis, and goblet cell metaplasia- have all been found to be important. In severe CAO, inflammation and fibrosis do not appear to be important, but goblet cell metaplasia, bronchiolar tortuosity, and narrowing do. Emphysema is a subset of airspace enlargement. Emphysema is defined anatomically and is the most important component of severe CAO. Several forms of emphysema can be recognized morphologically and may have specific clinical associations. However, in the usual patient with severe CAO, it is the severity, rather than the type, of emphysema, that is most significant. The diagnosis of emphysema depends on a combined approach. Significant factors include the clinical history (age, sex, smoking, chronic bronchitis, dyspnea), radiologic evidence of overinflation, and diminished diffusing capacity for carbon monoxide. PMID- 2205439 TI - The diagnosis of emphysema, chronic bronchitis, and asthma. AB - Although of some value for understanding etiologic mechanisms, the classic diagnostic categories of asthma and emphysema and especially chronic bronchitis have not served clinicians well for defining prognosis and therapeutic options. Until more useful diagnostic categories are available, the choice of diagnostic tests should be guided more by their clinical usefulness than by their sensitivity and specificity for identifying classic diagnostic categories of obstructive lung disease. A history consistent with asthma is as good evidence of asthma as that provided by most tests, especially if combined with spirometric evidence of complete reversibility of episodes of obstruction. Positive bronchial challenge studies and partial responses to bronchodilators are common in asthma but of limited diagnostic specificity. Tests of allergic function are of limited specificity for asthma, although a low IgE level is rare. Findings of reduced expiratory flows, high TLC, and low DLCO, or radiologic signs of hyperinflation, bullae, and pulmonary vascular deficiency pattern are useful for diagnosing cases of severe emphysema, but they are of limited sensitivity for the detection of mild to moderate disease. Advances in high resolution CT offer promise of earlier diagnosis of emphysema. Making a diagnosis of chronic bronchitis based on defined criteria for chronic sputum production is easy but of limited clinical value. Prospective longitudinal studies and advances in technology promise more clinically useful diagnoses in the future. PMID- 2205440 TI - Pharmacologic therapy of obstructive airway disease. AB - The pharmacologic treatment of chronic obstructive pulmonary disease (COPD) differs from that of asthma in several respects. Oral therapy should be the keystone, using a long-acting theophylline or a beta 2-sympathomimetic agent. The addition of a metered dose inhalant aerosol provides additive benefit with low toxicity; either a sympathomimetic agent or ipratropium or both should be used. The antiinflammatory aerosols, cromolyn, and steroid drugs are usually of no value, and oral steroids are only indicated if there is an asthmatic component. Mucokinetic agents and antibiotics should be used selectively. The numerous other drugs that may be required by a COPD patient must be prescribed with consideration to the potential for adverse physiologic effects and untoward drug interactions. PMID- 2205441 TI - Long-term home oxygen therapy. AB - Oxygen therapy improves mortality and morbidity in hypoxemic patients with COPD. For best results, oxygen should be administered continuously. The general guidelines that qualify a patient for long-term home oxygen therapy are rather explicit, although there are some gray areas, such as increasing exercise performance in normoxemic COPD patients and the treatment of dyspnea in certain patients. The physiologic goals of oxygen therapy are to reverse or prevent tissue hypoxia under the various conditions of life. Patients often experience a fall in oxygen saturation during REM sleep and during exercise. Thus, the oxygen prescription should specify the oxygen setting during wakeful rest, sleep, and exertion. Pulmonary rehabilitation is the definitive long-term management for patients with chronic lung diseases by building endurance, strength, and coping skills. Patients undergoing pulmonary rehabilitation are taught to become active and mobile. The rehabilitation programs have a special role in helping patients to accept and properly administer their own oxygen therapy. Oxygen therapy should be based on mobility and portability. Improvements in the weight and bulk of oxygen containers and the introduction of oxygen-conserving devices have rendered oxygen systems more portable and less costly. The prescription initiates a clinical triad relationship between the patient, physician, and home oxygen vendor. Prescribing home oxygen is now more time-consuming, and the prescription process requires the careful attention of the physician. The prescription must include patient data, the diagnostic reasons for oxygen, the blood gases, the type of system, and the liter-flow for the various living conditions such as rest, sleep, and exertion. Reimbursement for oxygen via Medicare and other carriers will depend upon the physiologic data as well as the successful completion of a rather complex form. Oxygen therapy should be monitored by regular arterial blood gases or pulse oximetry where appropriate. Patients should have a blood gas sample taken upon any change of condition or adjustment of the oxygen flow setting. Successful oxygen therapy should be physician directed, based on a solid understanding of the physiologic processes involved. PMID- 2205442 TI - Lung transplantation for chronic obstructive pulmonary disease. AB - Lung transplantation has been successfully employed for a variety of obstructive lung diseases. Following successful application of combined heart-lung transplantation, double lung transplant appeared to offer potential advantages but was hampered by the frequent development of donor airway complications. During the past 2 years single lung transplantation has been successfully employed with increasing frequency in the management of nonseptic obstructive lung disease. Although early results are encouraging, long-term follow-up is necessary to determine the ultimate indications for single lung, double lung, and combined heart-lung transplantation in patients with chronic obstructive lung disease. PMID- 2205443 TI - Prognosis in chronic obstructive pulmonary disease. AB - Although many factors have been shown to relate to survival in patients with COPD, the patient's age and baseline postbronchodilator FEV1 are the best predictors of mortality. The presence of mild obstructive airway disease is not indicative of a progressive downhill course and shortened survival. Mortality in patients with a baseline postbronchodilator FEV1 greater than or equal to 50% of predicted was only slightly greater than that of a group of healthy smokers. Investigators attempting to compare survival in patients with COPD should attempt to exclude patients with asthma or asthmatic bronchitis, because these individuals have a much better prognosis than those with typical COPD (emphysema and chronic bronchitis). Patients should be matched closely for age and severity of impairment, because younger individuals and those with milder impairment are likely to live longer. Other factors besides age and baseline FEV1 have been shown to affect survival. Patients who stop smoking are likely to survive longer than those who continue to smoke. The presence of malnutrition has clearly been shown to worsen survival. Further studies will be necessary to determine if corticosteroid therapy can slow down progression of disease in patients with typical COPD. Oxygen therapy improves survival in COPD patients with significant hypoxemia, many of whom also have CO2 retention, polycythemia, and cor pulmonale. There are now multiple studies in the literature suggesting that the type of comprehensive respiratory care provided by pulmonary rehabilitation programs can not only improve the quality of life but also survival in patients with chronic obstructive pulmonary disease. PMID- 2205444 TI - Finalists' papers from the 1989 SCAMC student paper competition at the Symposium on Computer Applications in Medical Care (SCAMC). Washington, DC, USA. PMID- 2205445 TI - Hypermedia and randomized algorithms for medical expert systems. AB - KNET is an environment for constructing probabilistic, knowledge-intensive systems within the axiomatic framework of decision theory. The KNET architecture defines a complete separation between the hypermedia user interface on the one hand, and the representation and management of expert opinion on the other. KNET offers a choice of algorithms for probabilistic inference. We and our coworkers have used KNET to build consultation systems for lymph-node pathology, bone marrow transplantation therapy, clinical epidemiology, and alarm management in the intensive-care unit. Most important, KNET contains a randomized approximation scheme (RAS) for the difficult and almost certainly intractable problem of Bayesian inference. Our algorithm can, in many circumstances, perform efficient approximate inference in large and richly interconnected models of medical diagnosis. In this article, we describe the architecture of KNET, construct a randomized algorithm for probabilistic inference, and analyze the algorithm's performance. Finally, we characterize our algorithms' empiric behavior and explore its potential for parallel speedups. From design to implementation, then, KNET demonstrates the crucial interaction between theoretical computer science and medical informatics. PMID- 2205446 TI - QUAWDS: a composite diagnostic system for gait analysis. AB - QUAWDS is a system for interpreting human gait. This task is complex because patients usually have multiple faults, and there is significant interaction between the components in the system. QUAWDS interprets a gait study by integrating associational and qualitative models of knowledge into a diagnostic system, taking advantage of the subtasks each kind of model can perform efficiently and effectively. An abductive hypothesis assembler is used to coordinate the subtasks. The result is a diagnostic solution that is 'locally best', i.e., no single change to the answer will produce a better solution. PMID- 2205447 TI - Multiple parameter assessment of vulvar irritant contact dermatitis. AB - Transepidermal water loss (TEWL), capacitance, pH, blood flow and color reflectance were evaluated for quantifying the irritant response of vulvar and forearm skin to 3% sodium lauryl sulfate in 9 healthy premenopausal women. TEWL, capacitance, pH, blood flow, and all parameters of color reflectance changed significantly in forearm irritant dermatitis. In vulvar irritant dermatitis, however, significant changes were observed only for blood flow and the color reflectance parameters a* and b*. Using the combination of TEWL, capacitance and blood flow, forearm irritant dermatitis was detected with a sensitivity of 84% and a specificity of 100%. In this study, the best combination of parameters to detect vulvar irritant dermatitis was pH, blood flow, a* and b*, which had a sensitivity of 78% and a specificity of 75%. It is concluded that available bioengineering techniques are less suitable to quantify irritant dermatitis in the vulva than in the forearm. PMID- 2205448 TI - Sexual transmission efficiency of hepatitis B virus and human immunodeficiency virus among homosexual men. PMID- 2205449 TI - Neuroblastoma. PMID- 2205450 TI - [Immunohistochemical analysis of HLA class I antigens of the hepatocyte membrane in hepatitis B virus carriers]. AB - HLA class I antigens on hepatocyte membrane were studied in liver biopsies from 46 patients with chronic hepatitis B virus infection by using immunoenzyme technique. The results revealed that the density of HLA class I antigens displayed on hepatocyte membrane in HBeAg positive carriers with minor hepatic inflammatory activity (the high replicative phase) was lower than that in patients with chronic active liver diseases (the low replicative phase) (P less than 0.005), but higher than that in patients with anti-HBe positivity and minor hepatic inflammatory activity (the nonreplicative phase) (P less than 0.05). In a follow-up of 21 HBeAg positive chronic HBV carriers, we found that five of the seven cases with high-density HLA class I antigens showed display of antigens on hepatocyte membrane, whereas only one of the 14 cases with lowdensity antigens were seroconverted from HBe antigen to antibody within one year. These findings suggest that the display on HLA class I antigens on hepatocyte membrane is enhanced and the cytotoxic T lymphacytes can recognize and lyze the infected hepatocytes. PMID- 2205451 TI - [The current status of nosocomial pneumonia]. PMID- 2205452 TI - [Fine needle aspiration biopsy of intrathoracic mass guided by real-time sonography--analysis of 50 cases]. AB - From May 1987 to February 1988, fine needle aspiration biopsy of intrathoracic mass guided by real-time sonography was performed in 50 consecutive patients and succeeded in 45 (90%). In this series, there were 34 malignant neoplasms with success rate of 94.12% and 16 benign lesions with success rate of 81.25%. Statistical analysis showed no difference. The success rates were different in various sites: supraclavicular 100% (3/3), parasternal 92.86% (13/14), paravertebral 75.00% (3/4), intercostal 89.66% (26/29). But, the statistical analysis was still not significant. No other complications occurred except mild hemoptysis in 1 case. Fine needle aspiration biopsy of intrathoracic mass guided by real-time sonography, being of simplicity, less complications and no exposure of either patient or operator to radiation, should be used widely. PMID- 2205454 TI - [Chromosomal localization of transforming oncogene BGC-Ha-ras in gastric cancer cell line]. AB - BGC-Ha-ras, isolated from the human gastric cancer cell line BGC-823 and activated by point mutation, is a transforming oncogene. To study whether this oncogene can still be located in the original position of chromosome 11 of BGC 823 cell line, chromosomal in situ hybridization method was used. The results showed that 31% silver grains were localized on chromosome 11, 83% of which on the 11p15 region, and in addition, 10% grains on distal end of the short arm of the other abnormal chromosome. Such results are significant in further study of the relation between gene localization and carcinogenesis. PMID- 2205453 TI - [Primary malignant lymphoma of the stomach--report of 6 cases and review of 586 cases]. AB - Six cases of primary malignant lymphoma in the stomach are reported with a review of 586 cases reported from 1950 through 1987 in our country. The disease is rare. The first case was reported abroad in 1829 and in our country in 1951. Abdominal pain, anorexia and hemorrhage in the gastrointestinal tract were the main symptoms. Surgery was the treatment of choice. The 5-year survival rate was 57.0% abroad and 44.6 at home. Adjuvant postoperative radiotherapy or chemotherapy can improve the 5-year survival. In the review, 5-year survival rate was increased by 6.8% in the group where surgery was combined with radiotherapy and by 5.7% in the group of operation plus chemotherapy. The increase in 10-year survival rate was more obvious. Of these 6 cases, 3 treated by surgical treatment alone died, while 3 treated by operation and postoperative chemotherapy are still alive and tumor free. PMID- 2205456 TI - [The diagnosis of chronic hepatitis]. PMID- 2205457 TI - [Secondary sulfonylurea failure]. PMID- 2205455 TI - Evaluation of the effects of L-acetylcarnitine on senile patients suffering from depression. AB - Twenty-eight patients aged between 70 and 80 years affected by depressive disturbance as defined by DSM III R (cat. 300.40) were subdivided at random into two homogeneous groups of 14 each. One group was treated with 500 mg three times a day of L-acetylcarnitine (LAC) in tablet form, while the other received placebo. Each patient was evaluated by the Hamilton Rating Scale for Depression, the Beck Depression Inventory, the Sandoz Clinical Assessment--Geriatric, and by clinical global impression. This investigation establishes that LAC is effective in counteracting symptoms of depression in the elderly. Relief of depressive symptomatology is expressed by decreased scores in the Hamilton Rating Scale for Depression and Beck Depression Inventory and by beneficial effects with regard to behavioural aspects. PMID- 2205459 TI - [Cultivation technics for freshwater fish]. AB - A general overview is presented on the various cultivation techniques in modern freshwater aquaculture. Included are overall production figures for finfish production in the most important producing countries of Europe. Major emphasis is placed on the situation of aquaculture development in the Federal Republic of Germany, providing details on the structure of the industry in the states of Bavaria, Lower Saxony, and Schleswig-Holstein. The trend towards intensification and its implications to system performance is described. The development of recirculation systems, particular for eel farming, is outlined, indicating the various problems related to system design, local conditions and species requirements. Future trends and research needs are identified. PMID- 2205458 TI - [Controversies around the prevention of stress bleeding]. PMID- 2205460 TI - [The pollution of water by fish feeding]. AB - Fish feeding causes water pollution by uneaten feeds, by faeces and by excretions via gills and kidneys. Pellet stability is essential for maximizing the consumed proportion of diets offered. At given water temperatures and feeding to satiation feed intake of trout its negatively correlated to dietary concentration of digestible energy. Increasing DE from 15 to 20 MJ per kg reduces feed conversion ratio from 1.33 to 1.00 and, concurrently, reduces the amount of organic matter voided in faeces from 680 to 230 g per kg weight gain of trout. For minimizing water pollution, trout diets containing 20 MJ DE per kg should not exceed 40% Protein and 0.6% P. PMID- 2205461 TI - [The food legislation evaluation of environmental chemicals in freshwater fish]. AB - During the last 1 1/2 decades different regulatory limits have been given to value pollutants in fish under food-legal aspects. Their requested target, which consists of an effective consumer's protection however has been missed by various reasons: The production and distribution of environmental pollutants cannot be suppressed by limits for food. The selective elimination of limit-exceeding individuals from a lot is impossible. Treating both, natural pollutants like geogenic mercury and anthropogenic ones similar seems to be indefensible with regard to food law. Therefore proposals are made to rule only anthropogenic pollutants by law, when regulatory limits are planned to be supplemented. In case of natural distribution less stringent advisory limits seem to be more suitable. PMID- 2205462 TI - [The occurrence of bacteria pathogenic for humans in freshwater fish]. AB - Freshwater fish are of minor importance as vectors of food-borne disease in humans. These diseases can only rarely be traced back to bacterial pathogens. However, there is a number of bacteria with facultative pathogenicity for man, which are part of the natural aquatic environment. Among these bacteria, the motile aeromonads (A. sp.) have become more and more important. A review is presented on A. sp. infections which have been traced back to contact with fish or water. Critical discussion of these cases reveals that the etiological relevance of A. sp. remains unclarified. However, bacteria of this group can be associated with sometimes fatal infections in humans after contact with fish or water. As A. sp. are ubiquitous in water and can survive even in chlorinated tap water, infections are not necessarily restricted to contact with fish. Persons at risk (patients with chronic or malignant diseases, immunocompromised hosts, children, people with frequent contact with water) should be informed about the perceived risks of aeromonads and how to avoid infection. Preventive measures are the wearing of gloves for work which may easily lead to skin abrasions (f. i. gutting of fish) and total abstinence of raw seafood. As their occurrence is independent of the common indicator bacteria, A. sp. are to be included in hygienic monitoring programmes for any water. PMID- 2205463 TI - [Drug residues in food fish]. AB - The present paper reviews different possibilities of pharmacolegal residues in fish. Sometimes the treatment of fish with registered drugs in therapeutical dosage is provable in spite of keeping the withdrawal time. To that experiences of the persistence and values of Chloramphenicol, Chlortetracycline and Furazolidone proved after therapeutical treatment in fish correlated to the water temperature are compared with results of experiments documented in literature. Investigations on the residues of Enrofloxacin after application of different doses to rainbow trout were carried out. Sometimes the proof of drug residues in fish can be done without an advanced treatment. The recontamination of fish with drugs or their metabolites in environment is discussed as a possibility for drug residues. The carry-over-effect of drug during the animal food production can be also the reason for residues in fish. Experiments with Chloramphenicol contaminated feed in rainbow trout show residues in muscle of fish higher than 10 ppb during the feeding period. Finally the results of residues different drug used in fish--given in literature--are collected in two tables. PMID- 2205464 TI - [Contributions on breeding published by the Insemination Association of Neustadt on-the-Aisch, Inc., and the "Dr. Dr. h.c. Karl Eibl" Foundation]. PMID- 2205465 TI - Mechanisms of neurulation: traditional viewpoint and recent advances. AB - In this review article, the traditional viewpoint of how neurulation occurs is evaluated in light of recent advances. This has led to the formulation of the following fundamentals: (1) neurulation, specifically neural plate shaping and bending, is a multifactorial process resulting from forces both intrinsic and extrinsic to the neural plate; (2) neurulation is driven by both changes in neuroepithelial cell shape and other form-shaping events; and (3) forces for cell shape changes are generated by both the cytoskeleton and other factors. Several cell behaviors within the neural plate have been elucidated. Future challenges include identifying cell behaviors within non-neuroepithelial tissues, determining how intrinsic and extrinsic cell behaviors are orchestrated into coordinated morphogenetic movements and elucidating the molecular mechanisms underlying such behaviors. PMID- 2205466 TI - Guidance of commissural growth cones at the floor plate in embryonic rat spinal cord. AB - The floor plate of the embryonic rat spinal cord has been proposed to act as an intermediate target that plays a role in the pattern of extension of commissural axons. To begin to examine the role of the floor plate in axon guidance at the midline, we have studied the precision of the commissural axon projection to and across the floor plate during development. To delineate the pathway, the fluorescent carbocyanine dye, Di-I, has been used as a probe. We show that commissural axons traverse the floor plate and turn rostrally at its contralateral border with remarkable precision. Axons were not observed to turn ipsilaterally and turned only upon reaching the contralateral edge of the floor plate. Virtually all commissural axons follow this route. The morphology of commissural growth cones was also examined. As they encountered the floor plate, commissural growth cones became larger and increased in complexity. The reorientation of axons in register with the floor plate boundary and the change in the morphological properties of commissural growth cones as they traverse the midline suggest that the floor plate may act as a guidepost with functions similar to cells that have been implicated in axon guidance in invertebrates. PMID- 2205467 TI - Lateral inhibition and the development of the sensory bristles of the adult peripheral nervous system of Drosophila. AB - Cells in the neurectoderm of Drosophila face a choice between neural and epidermal fates. On the notum of the adult fly, neural cells differentiate sensory bristles in a precise pattern. Evidence has accumulated that the bristle pattern arises from the spatial distribution of small groups of cells, proneural clusters, from each of which a single bristle will result. One class of genes, which includes the genes of the achaete-scute complex, is responsible for the correct positioning of the proneural clusters. The cells of a proneural cluster constitute an equivalence group, each of them having the potential to become a neural cell. Only one cell, however, will adopt the primary, dominant, neural fate. This cell is selected by means of cellular interactions between the members of the group, since if the dominant cell is removed, one of the remaining, epidermal, cells will switch fates and become neural. The dominant cell therefore prevents the other cells of the group from becoming neural by a phenomenon known as lateral inhibiton. They, then, adopt the secondary, epidermal, fate. A second class of genes, including the gene shaggy and the neurogenic genes mediate this process. There is some evidence that a proneural cluster is composed of a small number of cells, suggesting a contact-based mechanism of communication. The molecular nature of the protein products of the neurogenic genes is consistent with this idea. PMID- 2205468 TI - Coexistence of perinatal and adult forms of a glial progenitor cell during development of the rat optic nerve. AB - We have studied the developmental appearance of the O-2A(adult) progenitor cell, a specific type of oligodendrocyte-type-2 astrocyte (O-2A) progenitor cell that we have identified previously in cultures prepared from the optic nerves of adult rats. O-2A(adult) progenitors differ from their counterparts in perinatal animals (O-2A perinatal progenitor cells) in antigenic phenotype, morphology, cell cycle time, rate of migration, time course of differentiation into oligodendrocytes or type-2 astrocytes and sensitivity to the lytic effects of complement in vitro. In the present study, we have found that O-2A(adult) progenitor-like cells first appear in the developing optic nerve approximately 7 days after birth and that by 1 month after birth these cells appear to be the dominant progenitor population in the nerve. However, the perinatal-to-adult transition in progenitor populations is a gradual one and O-2A(adult) and O-2A perinatal progenitors coexist in the optic nerve for 3 weeks or more. In addition, cells derived from optic nerves of P21 rats express characteristic features of O-2adult and O-2A perinatal progenitors for extended periods of growth in the same tissue culture dish. Our results thus indicate that the properties that distinguish these two types of O-2A progenitors from each other are expressed in apparently identical environments. Thus, these cells must either respond to different signals present in the environment, or must respond with markedly different behaviours to the binding of identical signalling molecules. PMID- 2205469 TI - Otologic disease in the acquired immunodeficiency syndrome. AB - It appears that true otologic manifestations of AIDS are rare and that incidental otologic disease associated with AIDS is more common. A review of the literature revealed that otitis externa, acute otitis media, recurrent acute otitis media, otitis media with effusion, chronic suppurative otitis media with cholesteatoma, and herpes zoster oticus may all represent incidental otologic disease occurring in patients with AIDS. Chronic otitis media without cholesteatoma (P carinii infected aural polyps), sensorineural hearing loss, acceleration of otosyphilis from the latent stage, and development of Kaposi's sarcoma of the external auricle or nasopharynx may represent true otologic manifestations of AIDS. PMID- 2205470 TI - Sinusitis in patients with the acquired immunodeficiency syndrome. AB - AIDS patients suffer from multiple immunologic deficits involving humoral and cell-mediated immunity. The humoral deficits place the patient at a higher risk for recurrent bacterial infection than the general population. Sinusitis has been recognized to be a more common problem in AIDS patients than was previously appreciated. A high level of clinical suspicion is important, especially in patients with fever, headaches, or symptoms referrable to the upper respiratory tract. Should sinusitis be demonstrated, aggressive medical management is indicated. Surgical drainage is indicated in patients who worsen in spite of appropriate medical therapy, patients who have signs of systemic toxicity from the sinusitis that do not rapidly improve, and patients with recurrent sinusitis. Further studies are indicated to determine the true incidence of sinusitis in the AIDS population and to elucidate further the immunologic defects involved. PMID- 2205471 TI - Oral manifestations of human immunodeficiency virus infection. AB - It is important that both physicians and dentists recognize the earliest signs of HIV infection in order that a timely diagnosis and patient referral can be made for counseling and treatment. Candidiasis, hairy leukoplakia, and Kaposi's sarcoma are the most common oral manifestations, but there are other important lesions as well. They include severe necrotizing periodontitis, bacterial and viral infections, lymphomas, and carcinomas. The various oral lesions seen in patients with the acquired immunodeficiency syndrome are reviewed and managements are discussed. PMID- 2205472 TI - Lymphadenopathy in the HIV-seropositive patient. AB - The problem of lymphadenopathy in HIV-seropositive patients is reviewed, and indications for further study are presented. Implications for patients who later develop AIDS are discussed. PMID- 2205474 TI - Current issues in the development of a vaccine against HIV infection. AB - There are a variety of complex issues involved in current efforts to design and test a safe and effective vaccine against HIV-1 infection. Although a number of important insights already have been gained, future advances in vaccine development must overcome a number of obstacles. These include the lack of a suitable animal model for HIV-1 infection and our incomplete understanding of the protective immune response in this disease as well as uncertainties about the most appropriate strategy for large-scale testing of promising candidate vaccines. PMID- 2205473 TI - Current treatment for human immunodeficiency virus infection. AB - Treatment of human immunodeficiency virus (HIV) infection can prolong survival and enhance the quality of life in affected patients, although neither immune reconstitution nor cure can be achieved. Zidovudine is now the only licensed treatment. It is effective but sometimes toxic. Zidovudine decreases the incidence of opportunistic infections but does not prevent them, and concurrent prophylaxis against Pneumocystis carinii pneumonia should be given to those patients at greatest risk of this infection. Most patients should have serial CD4+ T-cell determinations to assess their degree of immunodeficiency. Many investigational anti-HIV agents are being studied, and future treatments are likely to use multiple agents in combination or in sequence over many years. PMID- 2205475 TI - Human liver growth hormone receptor and plasma binding protein: characterization and partial purification. AB - The human liver GH receptor has been further characterized using several biochemical approaches. Crosslinking of [125 I]human GH (hGH) to microsomal receptors and to particulate and solubilized plasma membrane receptors, followed by gel electrophoresis and autoradiography, revealed two predominant receptor hormone complexes with a mol wt of 124,000 and 75,000, respectively. As previously shown, the 70-80 k band appears to be generated from the 124 k band in the presence of beta-mercaptoethanol, suggesting intersubunit disulfide linkages. A minor complex of mol wt 150,000 was sometimes found. By immunoblot, using a polyclonal antibody raised against a synthetic peptide (residues 391-405 of the mature human GH receptor), a single band of 100 k was detected. Human liver GH receptor and plasma GH-binding protein (BP) were purified 1,000- and 4,000-fold, respectively. The partially purified membrane receptor, analyzed by ligand-blot, showed two major bands of 55 and 32 k and minor bands of 68 and 47 k. Crosslinking of the purified GH-BP or purified receptor with [125I]hGH revealed a 75 k receptor-hormone complex. Polyclonal antibodies raised against the hepatic GH receptor inhibited the binding of hGH to the human receptor and were able to immunoprecipitate the GH receptor and also the GH-BP complex. Our findings demonstrate the existence of multiple forms of the GH receptor in human liver (major components of 100 and 50-55 k, minor component of 130 k); they lend more support to the possible subunit structure of the GH receptor; and finally, they also suggest a close relationship, with common antigenic properties, of the membrane receptor and the plasma GH-BP. PMID- 2205476 TI - Demonstration of neuropeptide Y and its precursor in plasma and follicular fluid. AB - The present investigation provides three lines of evidence for the presence of a pro-form of neuropeptide Y (NPY) in plasma and follicular fluid. First, by the demonstration of NPY-immunoreactive material of a size corresponding to the estimated mol wt of pro-NPY. Second, an antiserum specific for the C-terminal tyrosine amide of NPY and peptide YY does not react with this material. Third, it was possible to convert the pro-NPY extracted from plasma and follicular fluid using the protease, Endoproteinase-Lys C, to a NPY-immunoreactive form eluting slightly before NPY on a G-50 column. The size of the digested product was consistent with a cleavage of pro-NPY resulting in an immunoreactive species, NPY Gly-Lys. Pro-NPY was also found in tissue culture media from the human neuroendocrine cell line SH-SY5Y. As in the case of plasma and follicular fluid, another NPY immunoreactive species eluted from a G-50 gel filtration column slightly before synthetic human NPY. Analysis of this material with an antibody directed against the tyrosine amide of NPY in combination with isoelectric focusing revealed that this peak consisted of at least two immunoreactive forms of NPY. In conclusion, at least three different forms of NPY immunoreactivity are likely to be present in plasma, follicular fluid, and cell tissue culture media; pro-NPY, a degradation form of pro-NPY, or a biosynthetic intermediate and NPY. PMID- 2205477 TI - Two glucocorticoid binding sites on the human glucocorticoid receptor. AB - Glucocorticoids are known to have a lytic effect in leukemic cells via interactions with the glucocorticoid receptor (GR). Cortisol and various synthetic glucocorticoids bind to the GR with one-site kinetics. Cortivazol (CVZ) is a unique, high potency synthetic glucocorticoid, which has a phenylpyrazol fused to the A-ring of the steroid nucleus and displays binding consistent with two or more sites in the cytosol from CEM C7 cells (a human acute lymphoblastic T cell line). It has previously been shown that the lower affinity class of sites are similar in affinity and site molarity to those recognized by dexamethasone. The higher affinity sites bind CVZ with 20- to 50-fold greater affinity, consistent with CVZ's enhanced biological effects. In mutant leukemic cells resistant to the lytic effects of dexamethasone, CVZ both lyses the cells and recognizes a single class of sites similar to the high affinity site in CEM C7 cells. We have carried out experiments to define the nature of the higher affinity CVZ binding site. We now show that: 1) CVZ has more than one binding site in a second, independent, B-cell line, IM-9; 2) the antiglucocorticoid RU 38486 is able to block both CVZ's higher and lower affinity sites; 3) all of CVZ's binding sites are on a protein immunologically indistinguishable from the human GR; and 4) freshly isolated clones of CVZ-resistant cells have lost all binding sites for CVZ. These data indicate that CVZ is recognizing two glucocorticoid binding sites on the human GR or a protein very similar to it. PMID- 2205478 TI - Hypothalamic prolactin stimulates the release of luteinizing hormone-releasing hormone from male rat hypothalamus. AB - Previous works from our laboratory and others have shown that there is a PRL-like immunoreactive protein with immunological, chromatographic, and biological characteristics identical to those of pituitary PRL, and this is widely distributed in the rat central nervous system. Since pituitary PRL is important in controlling hypothalamic LHRH release, we have hypothesized that hypothalamic PRL-like immunoreactive protein might serve a similar role, that of an endogenous neuromodulator influencing hypothalamic LHRH release. To this end, we have examined the effect of PRL antiserum and normal rabbit serum on the release of immunoreactive LHRH from rat hypothalamic fragments cultured in vitro. In the first experiment, LHRH release from hypothalami of intact rats, bathed in PRL antiserum (1:200 in Krebs-Ringer bicarbonate buffer), was significantly lower than that from hypothalami bathed in normal rabbit serum (1:200 in Krebs-Ringer bicarbonate buffer) for 90 min of incubation. It was, however, possible that the PRL, immunoneutralized in the first experiment, was material that represented contamination from pituitary PRL. Therefore, we repeated the experiment using hypothalami from animals that had been hypophysectomized 2 weeks before death. Again, PRL antibody significantly inhibited the release of LHRH compared with that by hypothalami incubated in normal rabbit serum. Since testosterone is important to LHRH synthesis, a third experiment was carried out using hypothalami from hypophysectomized male rats that had been implanted sc with testosterone containing capsules 72 h before death. By 72 h serum testosterone levels had normalized. PRL antibody added to medium containing hypothalamic explants from these animals substantially inhibited in vitro LHRH release, a pattern essentially similar to that seen in intact and hypophysectomized animals without testosterone replacement. From these studies we have concluded that hypothalamic PRL is an important neuromodulator that promotes the release of LHRH from the hypothalamus. Testosterone, at least under the experimental conditions employed, appears not to be essential in this hypothalamic PRL-LHRH interaction. PMID- 2205479 TI - Localization of the endogenous benzodiazepine ligand octadecaneuropeptide in the rat testis. AB - Diazepam binding inhibitor (DBI) is the precursor of a family of peptides, including an octadecaneuropeptide (ODN), which share with DBI the ability to specifically displace benzodiazepines (BZD) from their receptors. BZD receptors have been found not only in the brain, but also in a variety of peripheral tissues, including the testis. To clarify the role of ODN in the testis, we have investigated the localization of ODN in the rat testis using two different cytochemical approaches: immunocytochemistry and in situ hybridization. Immunocytochemical localization was achieved using rabbit antibodies developed against rat ODN. At the light microscopic level, immunostaining was exclusively located in interstitial cells; the seminiferous tubules were totally unlabeled. In the developing rat, immunostaining in the interstitial cells was first detected in an 18-day-old fetus. The immunolabeling increased as a function of age to reach a plateau at 40 days of age. The ultrastructural localization of ODN was achieved by immunogold staining. The gold particles were exclusively found in the cytoplasm of Leydig cells. HPLC analysis performed in adult rat testicular extracts revealed that immunoreactive material was detected in a peak eluted later than synthetic rat ODN. The cellular distribution of ODN was also studied by in situ hybridization using a 35S-labeled single stranded RNA probe complementary to DBI mRNA. Hybridization signal obtained at the light microscopic level was only detected over interstitial cells. The data obtained clearly indicate that in the rat, Leydig cells synthesize ODN and accumulate ODN-like immunoreactivity. Since Leydig cells have been shown to contain BZD receptors, it might be hypothesized that ODN and/or other DBI-related peptides can play a role in Leydig cell regulation. PMID- 2205481 TI - Familial aggregation of epilepsy and clefting disorders: a review of the literature. AB - Nine studies have attempted to address the issue of whether familial aggregation of epilepsy and clefting disorders exists. This is an important issue as a genetic predisposition to clefting among relatives of individuals with epilepsy could potentiate any teratogenic effects of antiepileptic drugs (AEDs). The summary relative risk estimate derived from published studies does not show that epilepsy and clefting disorders aggregate in families. Rather, these studies suggest that the clefting abnormalities in offspring of women with epilepsy receiving AEDs are most likely related to a teratogenic effect of these medications. PMID- 2205480 TI - Modulation of arginine-induced insulin and glucagon secretion by the hepatic vagus nerve in the rat: effects of celiac vagotomy and administration of atropine. AB - We hypothesized the existence of vagal arginine sensors in the liver which modulate arginine-induced pancreatic hormone secretion. The present study was carried out to examine the efferent pathways and receptor mechanisms from arginine sensors using selective vagotomies and autonomic drugs on the secretion of insulin and glucagon after ip injection of L-arginine (1 g/kg BW) in rats in an unanesthetized and unrestrained state. Hepatic vagotomy (sectioning of the hepatic branch of the vagus nerve) enhanced both plasma insulin and glucagon concentrations after ip arginine more than those in sham-vagotomized (control) rats. The effect of hepatic vagotomy was blocked by adding celiac vagotomy (sectioning of the celiac branches of the vagus nerve) or by previous administration of atropine methyl nitrate (10 mg/kg BW), but not by phentolamine (1 mg/kg BW) or propranolol (2 mg/kg BW). Celiac vagotomy alone did not affect the plasma insulin concentration; however, it reduced the plasma glucagon concentration after ip arginine compared to that in sham-vagotomized rats. Administration of atropine alone did not affect plasma insulin or glucagon concentrations after ip arginine. These results suggest that celiac branches of the vagus nerve act as efferent pathways to the pancreas through a muscarinic receptor mechanism in the hepatic arginine sensor-mediated pancreatic neuroendocrine system. The physiological role of these hepatic sensors may be to prevent arginine-induced exaggerated pancreatic hormone secretion and maintain blood glucose homeostasis. PMID- 2205482 TI - Environmental epidemiologic investigations in the styrene-butadiene rubber production industry. AB - A review of the literature and an update that is in progress of a previous retrospective cohort mortality study of the styrene-1,3-butadiene industry are discussed. The follow-up has now been extended from April 1, 1976, through December 31, 1981, for plant B and December 31, 1982, for plant A. The person years at risk of death have gone from 34,187 to 43,341 in plant A and from 19,742 to 26,314 in plant B. Among the death certificates received to date, observed deaths have increased in both plants, with increases in cancers of the trachea, bronchus and lung and in lymphosarcomas, reticulosarcomas, and cancers of the overall lymphatic and hematopoietic system. PMID- 2205483 TI - Assessment of 1,3-butadiene epidemiology studies. AB - Positive carcinogenicity studies in mice and rats have led to concerns that 1,3 butadiene may be carcinogenic in humans under exposure conditions that have existed in occupational settings and perhaps exist today. The principal settings of interest are the styrene-butadiene rubber (SBR) manufacturing industry, which uses large quantities of 1,3-butadiene, and the 1,3-butadiene monomer industry. The potential for 1,3-butadiene exposure is highest during monomer transfer operations and is lowest in finishing areas of polymerization plants where the polymer products are processed. Three large cohort mortality studies have been conducted in the SBR and monomer producing industries since 1980. These studies, which examined the mortality experience of over 17,000 men employed in one monomer and 10 SBR facilities, are the subject of this review. All but one of the facilities began operations during the early 1940s. The mortality experience observed within these employee cohorts is comparable to that seen in other long term studies of men employed in the petroleum, chemical, and rubber industries for all causes of death, total malignant neoplasms, and for the specific cancers seen in excess in the toxicologic studies. This paper discusses discrepant findings observed in more detailed analyses within individual cohorts and among employment subgroups, as well as selected limitations of the particular studies. Additional efforts to refine 1,3-butadiene exposure categories are needed. Within the context of sample size limitations inherent in these studies, there is currently inadequate evidence to establish a relationship between cancer mortality outcomes and 1.3-butadiene exposure in humans. PMID- 2205484 TI - Critical assessment of epidemiologic studies on the human carcinogenicity of 1,3 butadiene. AB - 1,3-Butadiene, a major ingredient of synthetic rubber, has been shown to be carcinogenic in two animal species. To assess the possible human carcinogenicity of 1,3-butadiene, a critical review was undertaken of the epidemiologic literature. An early retrospective study of 8017 males employed in tire manufacturing found excess mortality for lymphatic and hematopoietic neoplasms in production workers (standardized mortality ratio, SMR = 560); these workers were exposed to 1,3-butadiene as well as to styrene and possibly to benzene. A recently updated epidemiologic study of 2568 workers at a butadiene manufacturing plant in Texas reported low mortality overall (SMR = 84) but found excess deaths for lymphosarcoma and reticulum cell sarcoma (SMR = 229). A retrospective study of workers employed at two synthetic rubber plants in Texas found excess mortality for lymphatic and hematopoietic malignancies in the older of these facilities; the excesses for lymphosarcoma (SMR = 224) and leukemia (SMR = 278) were most significant in wartime workers. A large, recently updated retrospective study of 12,113 workers employed in eight synthetic rubber manufacturing plants in the United States and Canada found excess mortality for lymphatic and hematopoietic cancer in production workers; the SMR for other lymphatic cancers in white production workers was 230, and the SMR for all lymphatic malignancies in black production workers was 507. These updated epidemiologic results strongly suggest an etiologic association between occupational exposure to 1,3-butadiene and human cancer. It is reasonable, therefore, to conclude that there now exists at least limited evidence for the human carcinogenicity of 1,3-butadiene. PMID- 2205485 TI - Cancer risk assessment of 1,3-butadiene. AB - This paper discusses the Environmental Protection Agency's (EPA) risk assessment of 1,3-butadiene. The assessment focuses on estimation of increased cancer risk to populations living near industrial sources of 1,3-butadiene emissions rather than occupationally exposed populations. Incremental cancer risk estimates based on extrapolation from laboratory animal data are presented. Pharmacokinetic data published since the EPA's 1985 assessment are incorporated, which somewhat alters the earlier assessment of cancer risk. Characterization of emission sources, estimates of ambient air concentrations, and population exposure are also discussed. The estimate presented in this paper of excess cancer cases resulting from point source exposure to 1,3-butadiene is decreased to approximately 40% of the estimate published in 1985 from 6.4 in 10 to 2.5 chances in 10 for a lifetime exposure to 1 ppm. The current estimate is no more than eight additional cancer incidences in the general population. Increased risk to the most exposed individuals is not anticipated to be greater than 1 in 10. This reduction in the risk estimate is due to a change in the estimate of 1,3-butadiene potency (i.e., incremental unit risk estimate) based on incorporation of new pharmacokinetic data. PMID- 2205486 TI - Assessment of the potential risk to workers from exposure to 1,3-butadiene. AB - The available epidemiologic data provide equivocal evidence that 1,3-butadiene is carcinogenic in humans; some available studies suggest that the lymphopoietic system is a target, but there are inconsistencies among studies in the types of tumors associated with 1,3-butadiene exposure, and there is no evidence of a relationship between length of exposure and cancer risk, as one might expect if there was a true causal relationship between 1,3-butadiene exposure and cancer risk. The available chronic animal studies, however, show an increase in tumor incidence associated with exposure to high concentrations of 1,3-butadiene. In addition to the general uncertainty of the relevance of animal data to humans, there are several additional reasons why the National Toxicology Program's mouse study may not be appropriate for assessing possible human risks. These include: a) the possible involvement of a species-specific tumor virus (MuLV) in the response in mice; b) apparent differences between mice and humans in the rate of metabolism of 1,3-butadiene to reactive epoxides that may be proximate carcinogens; c) use of high dose levels that caused excess early mortality; and d) exposure of animals to 1,3-butadiene for only about half their lifetime. While recognizing the uncertainty in using the available animal data for risk assessment, we have performed low-dose extrapolation of the data to examine the implications of the data if humans were as sensitive as rats or mice to 1,3 butadiene, and to examine how the predictions of the animal data compare to that observed in the epidemiologic studies. With the mouse data, because the study was of less than lifetime duration, we have used the Hartley-Sielken time-to-tumor model to permit estimation of lifetime risk from the less than lifetime exposure of the study. With the rat data, we have used three plausible models for assessing low-dose risk: the multistage model, the Weibull model, and the Mantel Bryan probit model. With both the rat and mouse data, we used information on how much 1,3-butadiene is retained by animals exposed to various concentrations of the chemical. This improves the accuracy of the low-dose extrapolation. When extrapolated to low-dose levels, mice appear to be at greater risk (by a factor of 5-fold to 40-fold) than rats. Some of this difference (a factor 3-fold to 5 fold) may be due to the faster rate of metabolism of 1,3-butadiene to, and higher blood levels of, epoxide derivatives in mice than in rats.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2205487 TI - Lead toxicity: from overt to subclinical to subtle health effects. AB - Although the toxicity of lead was recognized centuries ago, concern was restricted to overt symptoms: colic, encephalopathy, anemia, or renal disease. Two major reasons for lack of progress in restricting toxicity were that interest was limited to occupational exposures and there was lack of awareness of specific biochemical or metabolic effects. Identification of subclinical effects has been possible the last 15 or 20 years because of the development of sensitive measures to detect cognitive and behavioral changes that are not apparent clinically and because of methods to measure the reduced activity of heme enzymes. This progress was driven by basic and clinical research that resulted in a better understanding of cellular toxicology. The new awareness prompted the lowering of acceptable occupational exposures, as measured by blood lead from 80 to 40 to 60 micrograms/dL range, and the establishment of maximum recommended exposures in children to a blood lead level of 25 micrograms/dL. Lowering the lead content in gasoline has been accomplished by a nearly 50% decrease in average blood levels of persons in the United States (NHANES II data). Current research implicates lead as a contributing etiologic factor in a number of common diseases affecting large portions of the population such as subtle cognitive and neurological deficits, hypertension, congenital malformations, immunotoxicity, and deficits in growth and development. For each of these disorders there may be multiple etiologic factors; the scientific challenge is to develop sensitive methodology to detect the specific role of lead. Other potential subtle health effects include the influence of small amounts of lead on cell proliferation and lead as a cofactor in carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2205488 TI - What can the study of lead teach us about other toxicants? AB - The history of knowledge about lead toxicity may serve as a useful template to judge and predict progress in understanding other toxicants. A paradigm shift has occurred in which toxicity has been recognized at levels long held to be harmless. This shift has been accelerated by the use of newer tools for measuring outcome. Lead effects have been identified in children at blood lead levels as low as 15 micrograms/dL. They include impaired psychometric intelligence, language function, attention, and classroom behavior. Lead exposure during pregnancy results in increased risk for minor malformations and lowered infant IQ scores until at least 2 years of age. Understanding of this toxicant has been blurred by seven unrecognized Type II errors frequently encountered in the lead literature. These errors are discussed. A meta-analysis of thirteen informative lead studies in children is presented. The joint probability of the findings occurring by chance under the null hypothesis is less than 3 x 10(-12). PMID- 2205489 TI - Toward the twenty-first century: lessons from lead and lessons yet to learn. AB - A consideration of recent research on lead is instructive for developing research strategies in environmental toxicology. Lead research has demonstrated fruitful interactions between clinical and basic science. Thus, while epidemiological studies have suggested that central nervous system (CNS) effects in children are observed at the lowest increments of lead exposure, basic research has elucidated some of the molecular events that underly this lack of threshold at the neuronal level. Similarly, clinical studies indicate that early exposure to lead produces functionally irreversible damage to the CNS; experimental research demonstrates that this irreversibility may involve failure to remove lead from brain, permanent effects on synaptogenesis; and chelant-induced redistribution of lead from the periphery to the CNS. Lead toxicokinetics demand reevaluation. New data on release of bone stores of lead during physiological conditions of demineralization indicate that mobilization of bone lead adds to in utero exposure of the fetus. Furthermore, postmenopausal demineralization of bone can increase blood lead levels in women by 25%; this raises concern about the potential effects of lead in an aging population and the difficulties in comprehensive exposure assessment. PMID- 2205490 TI - Implications of aquatic animal health for human health. AB - Human health and aquatic animal health are organically related at three distinct interfaces. Aquatic animals serve as important contributors to the nutritional protein, lipid, and vitamin requirements of humans; as carriers and transmitters of many infectious and parasitic diseases to which humans are susceptible; and as indicators of toxic and carcinogenic substances that they can convey, in some part, from aquatic environments to man and other terrestrial animals. Transcending these relationships, but less visible and definable to many, is the role that aquatic animals play in the sustenance of our integrated planetary ecosystem. Up to the present, this ecosystem has been compatible with mankind's occupation of a niche within it at high but ultimately limited population levels. In the past century we have become clearly aware that human activities, particularly over-harvesting of aquatic animals together with chemical degradation of their habitats, can quite rapidly lead to perturbances that drastically shift aquatic ecosystems toward conditions of low productivity and impaired function as one of earth's vital organs. The negative values of aquatic animals as disease vectors are far outweighed by their positive values as nutritional sources and as sustainers of a relatively stable equilibrium in the global ecosystem. In the immediate future we can expect to see increased and improved monitoring of aquatic habitats to determine the extent to which aquatic animals cycle anthropogenic toxic and carcinogenic chemicals back to human consumers. In the long term, methods are particularly needed to assess the effects of these pollutants on reproductive success in aquatic communities and in human communities as well. As inputs of habitat-degrading substances change in quality and quantity, it becomes increasingly urgent to evaluate the consequences in advance, not in retrospect. A new, more realistic and comprehensive philosophy regarding aquatic environmental preservation and equally new and comprehensive technological advances reflective of this philosophy will be required. In the next century we will see a serious test of whether or not mankind has lost its ability to foresee and forestall the side effects of scientific and technological ingenuity. PMID- 2205492 TI - An overview of prechronic and chronic toxicity/carcinogenicity experimental study designs and criteria used by the National Toxicology Program. AB - Since the establishment of the National Toxicology Program (NTP), there have been gradual changes in strategies to evaluate the overall toxicity of chemicals as well as their carcinogenic potential. The spectrum of toxicologic information sought on selected chemicals has been broadened by the multidisciplinary approach to evaluating chemicals. This paper describes the scientific rationale and experimental processes used by NTP in designing studies. Also, an outline of current NTP protocols are given for prechronic and chronic toxicity/carcinogenicity studies. PMID- 2205493 TI - The industrial production and use of 1,3-butadiene. AB - This presentation provides a brief overview of the production and use of 1,3 butadiene in the United States. Starting as a coproduct of ethylene, the 1,3 butadiene monomer is extracted and purified, then transferred to consumers. Major uses of 1,3-butadiene include the manufacture of styrene-butadiene rubber, polybutadiene rubber, and adiponitrile. PMID- 2205491 TI - Joint actions of environmental nonionizing electromagnetic fields and chemical pollution in cancer promotion. AB - Studies of environmental electromagnetic (EM) field interactions in tissues have contributed to a new understanding of both normal growth and the biology of cancer in cell growth. From cancer research comes a floodtide of new knowledge about the disruption of communication by cancer-promoting chemicals with an onset of unregulated growth. Bioelectromagnetic research reveals clear evidence of joint actions at cell membranes of chemical cancer promoters and environmental electromagnetic fields. The union of these two disciplines has resulted in the first major new approach to tumor formation in 75 years, directing attention to dysfunctions in inward and outward streams of signals at cell membranes, rather than to damage DNA in cell nuclei, and to synergic actions of chemical pollutants and environmental electromagnetic fields. We are witnesses and, in great measure, participants in one of the great revolutions in the history of biology. In little more than a century, we have moved from organs, to tissues, to cells, and finally to the molecules that are the elegant fabric of living tissues. Today, we stand at a new frontier. It may be more difficult to comprehend, but it is far more significant; for it is at the atomic level, rather than the molecular, that physical, rather than chemical, processes appear to shape the flow of signals that are at the essence of living matter. To pursue these problems in the environment and in the laboratory, our needs for further research with appropriate budgets are great.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2205494 TI - In vitro and in vivo genotoxicity of 1,3-butadiene and metabolites. AB - 1,3-Butadiene and two major genotoxic metabolites 3,4-epoxybutene (EB) and 1,2:3,4-diepoxybutane (DEB) were used as model compounds to determine if genetic toxicity findings in animal and human cells can aid in extrapolating animal toxicity data to man. Sister chromatid exchange (SCE) and micronucleus induction results indicated 1,3-butadiene was genotoxic in the bone marrow of the mouse but not the rat. This paralleled the chronic bioassays which showed mice to be more susceptible than rats to 1,3-butadiene carcinogenicity. However, 1,3-butadiene did not induce unscheduled DNA synthesis (UDS) in the rat or mouse hepatocytes following in vivo exposure. Likewise, UDS in rat and mouse hepatocytes in vitro was not induced by EB or DEB. Salmonella typhimurium gene mutation (Ames) tests of 1,3-butadiene using strains TA1535, TA97, TA98, and TA100 and employing rat, mouse, and human liver S9 metabolic systems were barely 2-fold above background only in strain TA1535 at 30% 1,3-butadiene in air with induced and uninduced rat S9 and mouse S9 (uninduced). 1,3-Butadiene was negative in in vitro SCE studies in human whole blood lymphocytes cultures treated in the presence of rat, mouse, or human liver S9 metabolic activation. In general, 1,3-butadiene is genotoxic in vivo but is a weak in vitro genotoxin. PMID- 2205495 TI - Overview of reproductive and developmental toxicity studies of 1,3-butadiene in rodents. AB - A series of studies to further evaluate the developmental and reproductive toxicity of inhaled 1,3-butadiene was sponsored by the National Toxicology Program. Pregnant Sprague-Dawley rats (24-28/group) and Swiss (CD-1) mice (18 22/group) were exposed to atmospheric concentrations of 0, 40, 200, or 1000 ppm 1,3-butadiene for 6 hr/day on days 6 through 15 of gestation (dg) and killed on dg 18 (mice) or dg 20 (rats). Subsequently, the uterine contents were evaluated; individual fetal body weights were recorded; and external, visceral, and skeletal examinations were performed. In rats, maternal toxicity was observed in the 1000 ppm group in the form of reduced extragestational weight gain and, during the first week of treatment, decreased body weight gain. Under these conditions, there was no evidence of developmental toxicity in rats. In contrast, results of the mouse developmental toxicity study indicated that the fetus may be more susceptible than the dam to inhaled 1,3-butadiene. Maternal toxicity was observed in mice at the 200- and 1000-ppm 1,3-butadiene exposure levels, whereas 40 ppm and higher concentrations of 1,3-butadiene caused significant exposure-related reductions in the mean body weights of male fetuses. Mean body weights of female fetuses were also reduced at the 200- and 1000-ppm exposure levels. No increased incidence of malformations was observed in either study. Other studies addressing male reproductive and mutagenesis end points were performed with B6C3F1 mice (sperm-head morphology) and Swiss (CD-1) mice (dominant lethal study).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2205497 TI - Nonribosomal biosynthesis of peptide antibiotics. AB - Peptide antibiotics are known to contain non-protein amino acids, D-amino acids, hydroxy acids, and other unusual constituents. In addition they may be modified by N-methylation and cyclization reactions. Their biosynthetic origin has been connected in many cases to an enzymatic system referred to as the 'thiotemplate multienzymic mechanism'. This mechanism includes the activation of the constituent residues as adenylates on the enzymic template, the acylation of specific template thiol groups, epimerization or N-methylation at this thioester stage, and polymerization in the sequence directed by the multienzymic structure with the aid of 4'-phosphopantetheine as a cofactor, including possible cyclization or terminal modification reactions. The reaction sequences leading to gramicidin S, tyrocidine, cyclosporine, bacitracin, polymyxin, actinomycin, enniatin, beauvericin, delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine and linear gramicidin are discussed. The structures of the multienzymes, their genetic organization, the biological functions of these peptides and results on related systems are discussed. PMID- 2205496 TI - Future directions--toxicology studies of 1,3-butadiene and isoprene. AB - Examination of a profile of data already existing on 1,3-butadiene shows adequate knowledge in many areas of toxicology that are conventionally required in hazard identification. However, while much progress has been made in areas of metabolism and pharmacokinetics, further studies would be worthwhile to improve mechanistic understanding such as the examination of alternate metabolic pathways, the generation of interspecies scaling factors, and an assessment of the relevance of various tumor sites. In this respect, data pertaining to repeated and pulse exposures of rodents and primates would be helpful. Another important aspect is the need to understand any human health implications of the observed 1,3 butadiene-induction of the murine leukemia virus. In this respect, studies have been pursued that include the comparison of leukemogenesis in congenetic strains, the leukemogenicity of viral isolates in rodent carcinogenicity and human cell culture studies, and the mechanisms of activation of ecotropic proviral sequences. Molecular epidemiological and toxicological research is ongoing in rodents and primates to evaluate hemoglobin adduct formation as an index of 1,3 butadiene exposure. Challenges of specificity, sensitivity, and simplification of current procedures need to be overcome. Recent mutagenicity and metabolism data suggest that structurally-related isoprene may have carcinogenic potential. The use of interstrain comparative studies and data in a second species is discussed, as well as proposed metabolism studies. PMID- 2205498 TI - Expression of the chemically synthesized coding region for the cytotoxin alpha sarcin in Escherichia coli using a secretion cloning vector. AB - The coding region for the cytotoxin alpha-sarcin from Aspergillus giganteus has been chemically synthesized by the ligation of 19 overlapping oligodeoxyribonucleotides. An Escherichia coli clone producing the cytotoxin was constructed by inserting the synthesized gene directly downstream to the region coding for the signal peptide of the OmpA protein (a major outer membrane protein of E. coli), using the secretion cloning vector pIN-III-OmpA2. The enzyme encoded by the chemically synthesized gene expressed in E. coli displayed properties identical to those of native alpha-sarcin isolated from A. giganteus with respect to its chemistry, antigenicity and ribonucleolytic activity in qualitative assays. PMID- 2205499 TI - Primary structure requirements for the maturation in vivo of penicillin acylase from Escherichia coli ATCC 11105. AB - The two constituent subunits of the enzyme penicillin acylase from Escherichia coli strain ATCC 11105 are derived from a single precursor polypeptide by post translational processing. Mutant penicillin acylase precursors were constructed carrying insertions and deletions in various domains and they were analysed for their processing behaviour. It was found that an endopeptide region of appropriate size and an intact C-terminus were absolutely necessary for the maturation process. Internal deletions within the beta-subunit domain also prevented post-translational cleavage. Processing competence, therefore, was not merely determined by the amino acid sequence in the vicinity of the processing sites but relied on a correct overall conformation of the protein. The processing pathway in vivo proceeds via an intermediate comprising the alpha subunits plus endopeptide and is thus identical to the pathway which has been determined previously by in vitro analysis. The post-translational modification of the precursor is probably not carried out by a specific processing enzyme(s) as the heterologous expression of the penicillin acylase (pac) structural gene yielded processed and active enzyme in different enterobacteria and in a Pseudomonas species. PMID- 2205500 TI - Citrate lyase from Klebsiella pneumoniae. The complete primary structure of the acyl lyase subunit. AB - The primary structure of the beta-subunit (acyl lyase subunit) of citrate lyase from Klebsiella pneumoniae (ATCC 13,882) was determined with protein chemical methods. The polypeptide chain consists of 289 amino acid residues and has a molecular mass of 31,352 Da. The two half-cystine residues of the subunit are present as cysteines and not involved in disulfide bridges. The sequence shows no homology to known sequences of proteins or nucleic acids and reads (sequence; see text) PMID- 2205501 TI - Renin-producing renal cell carcinoma. AB - The pathogenetic relationship between tumor and hypertension was investigated in 40 patients with renal cell carcinoma. 15 of 40 patients were hypertensive. Four of these 15 patients with renal tumors and hypertension (26.7%) were found to have primary reninism. In these patients the plasma renin activity in blood from the renal veins showed a tumor kidney to contralateral kidney ratio of between 6 and 7. In the same 4 cases the renin content in the renal tumor tissue was significantly higher than that in tissue from the adjacent tumor-free renal cortex of the ipsilateral kidney. Immunocytochemical demonstration of renin in the tumor was only possible in these 4 cases. In 3 of these patients blood pressure returned to normal following nephrectomy; in the 4th case there was a drop in blood pressure after nephrectomy. Renin-producing renal cell carcinomas are an uncommon cause of renal hypertension. The differential diagnosis of hypertension should therefore also include renal tumor. PMID- 2205502 TI - Nephrogenic adenoma of the bladder in a child--immunohistochemical and lectinhistochemical investigations. AB - A morphological study of a 6-year-old girl with a nephrogenic adenoma of the bladder is presented. The tumor developed 4 years after multiple reconstructive operations of the urinary tract. Immuno- and lectinhistochemically, the tubular structure of the lesion resembled that of a collecting tubule. A conservative approach was the treatment of choice in the absence of microscopically malignant changes. PMID- 2205503 TI - Simple surgical procedure for urinary stress incontinence. AB - A simple and efficient procedure is described for urinary stress incontinence. 28 patients have been operated in 10 years and the results are satisfactory to date. PMID- 2205504 TI - Xanthogranulomatous pyelonephritis associated with renal cell carcinoma. Report on two cases and review of the literature. AB - Xanthogranulomatous pyelonephritis is a rare and particularly aggressive variant of chronic destructive pyelonephritis. Even when all modern diagnostic possibilities are exhausted, it is often not possible to distinguish xanthogranulomatous pyelonephritis from a renal cell carcinoma preoperatively. In clinical practice false diagnoses are therefore frequent. The coexistence of xanthogranulomatous pyelonephritis and renal cell carcinoma is extremely rare. We report 2 such cases. In 1 case surgery was performed on the kidney affected by xanthogranulomatous pyelonephritis using a renal sparing technique. PMID- 2205505 TI - Effect of apomorphine on oxytocin concentrations in different brain areas and plasma of male rats. AB - The effect of the dopamine (DA) agonist, apomorphine, on oxytocin concentrations in the hypothalamus, hippocampus, septum and plasma was studied in male rats. Apomorphine dose dependently increased the concentration of oxytocin in the plasma and hippocampus, the minimal effective dose being 80 micrograms/kg s.c., which induced a 65% increase in plasma and a 45% increase in the hippocampus. The maximal effect (210 and 125% above controls) was induced with 240 micrograms/kg s.c. In contrast, there was a significant decrease (32%) in the oxytocin concentration in the hypothalamus, but only after the highest doses of apomorphine, while no change was found in the septum. The apomorphine effect in the hippocampus and hypothalamus was prevented by the mixed DA D-1/D-2 receptor blocker, haloperidol (0.3 mg/kg i.p.), and by the DA D-2 receptor blocker, (-) sulpiride (20 mg/kg i.p.), but not by the DA D-1 receptor blocker, SCH 23390 (0.2 mg/kg s.c.). Similar effects were found in plasma, although SCH 23390 inhibited the apomorphine effect by 45%. Our results suggest that apomorphine stimulates oxytocinergic transmission in male rats and provide biochemical support for the hypothesis that a DA-oxytocin link exists in the central nervous system. PMID- 2205506 TI - GABA does not protect cerebro-cortical cultures against excitotoxic cell death. AB - The effects of gamma-aminobutyric acid (GABA) and selective agonists of GABAA and GABAB receptors were examined on excitotoxic cell death evoked in primary cultures of the rat cerebral cortex by glutamate and related excitotoxins. The activity of lactate dehydrogenase released from irreversibly damaged cells into the culture medium was taken as a measure of cell death. Neither GABA nor its agonists protected the cerebro-cortical cells against the toxicity caused by glutamate, N-methyl-D-aspartate, quisqualate and kainate. It is concluded that the cerebro-protective activity of GABA demonstrated in situ involves indirect mechanisms rather than a direct effect on vulnerable cells. PMID- 2205507 TI - Neuropeptide Y selectively potentiates N-methyl-D-aspartate-induced neuronal activation. PMID- 2205508 TI - Long-term stability of the lower labial segment relative to the A-Pog line. AB - Cephalometric records of 47 cases treated with the Begg technique were examined with a view to assessing both the effects of treatment and long-term change. The cases were treated by a single operator (Dr H. Brouwer) whose long-term records were taken on average over 10 years out of retention. Special reference was made of the use of A-Pog line as a guide to lower incisor stability. There was marked individual variation in both response to treatment and long-term change. Though all the results were clinically stable the A-Pog line was not found to be a reliable guide to lower incisor stability. In 62 per cent of the cases examined, the lower incisors tended to return towards their original positions after retention, whilst in the remaining cases the changes were extremely variable. PMID- 2205509 TI - Changes in CGRP-immunoreactive nerve fibres during experimental tooth movement in rats. AB - Immunohistochemical localization of calcitonin gene-related peptide (CGRP) was used to investigate changes in nerves expressing CGRP in periodontium and pulp during experimental mesial movement of the first maxillary molar in rats. The orthodontic appliance consisted of a coil spring connecting the first maxillary molar on one side to the central incisors. After 5 days with a continuous force of 30-50 g the animals were perfused after an overdose of anaesthetic. Serial sections from the experimental and control jaws were exposed to the avidin-biotin peroxidase technique for demonstration of CGRP-immunoreactive (IR) nerve fibres. The induced tooth movement caused reproducible changes in the relative number of CGRP-IR nerves as well as morphological alterations within parts of the nerve supply of the experimental teeth and related tissue structures. The majority of the experimental teeth showed increased number of CGRP-IR nerves in the coronal pulp and periapical tissues. The results indicate that peptidergic nerve fibres immunoreactive for CGRP takes an active part in tissue responses in pulp and supporting tissues during experimental tooth movement. PMID- 2205510 TI - Expression of HLA by the human trabecular meshwork and corneal endothelium. AB - By using immunohistochemical techniques, we demonstrated that HLA class I (A, B and C) and HLA class II (DR), the major histocompatibility antigens in man, are expressed constitutively by cells of the trabecular meshwork/Schlemm's canal system and corneal endothelium, as well as by the conjunctival epithelium, Langerhans cells, vascular endothelium and uvea. Because clinical studies indicate that these antigens are involved in mediating corneal graft rejection and possibly in glaucomatous disease of the eye, the presence of both class I and II HLA in the corneal endothelium and in the trabecular cells has important implications for an understanding of immune disorders in the anterior segment of the eye. The presence of HLA on trabecular cells raises the possibility that these antigens potentiate the recognized role of Langerhans cells at the limbus and that they participate in, and/or regulate, the maintenance and defense of the aqueous outflow pathway. Our findings also open up the possibility of using HLA as a genetic marker in the determination of susceptibility to these disorders in man. PMID- 2205511 TI - Macrophage products IL-1 alpha, TNF alpha and bFGF may mediate multiple cytopathic effects in the developing eyes of GM-CSF transgenic mice. AB - GM-CSF transgenic mice develop eye disease during ontogeny that is mediated by autostimulated macrophages. The ocular pathology is characterized in part by corneal and vitreous neovascularization, pronounced GFAP expression by retinal Muller cells and degeneration of the retinal photoreceptor layer. The invading intraocular macrophages express the genes for the cytokines interleukin-1 alpha, tumor necrosis factor alpha and basic fibroblast growth factor, which may contribute to the multifaceted developmental ocular disorder. These cytokines, suspected to be angiogenic, may be responsible for neovascularization of the cornea in our transgenic animals. GFAP is normally made by astrocytes in the superficial retina and is induced in Muller cells in models of retinal degeneration. This protein is abnormally and copiously produced by Muller cells in the transgenic mice, which we suggest may be due to the release of cytokines from the invading macrophages. We suggest a mechanism by which autostimulated macrophages, through a perturbation of their normal developmental role, may be responsible for photoreceptor cell death in these transgenic animals. PMID- 2205512 TI - The clearance of heterologous antibodies in experimental antibasement membrane antibody mediated glomerulonephritis. AB - A study of the clearance of anti GBM antibodies is important for an understanding of the pathogenesis of Goodpasture's syndrome. This paper reports a study of the sequential clearance of heterologous anti-glomerular basement membrane antibodies in the neonatal rat. A single intraperitoneal injection was followed by rapid and linear binding of injected antibodies to glomerular basement membranes, particularly to those glomeruli in the corticomedullary region. GBM bound antibodies were cleared gradually through the mesangium and significant amounts of antibodies still remained bound after 6 months. Subsequent injections of antibodies failed to provoke morphological abnormalities. These experiments have shown that the glomerular basement membrane of neonatal and adult rats possesses similar antigenic sites. The mesangium plays a major role in the clearance of injected heterologous antibodies. The slow clearance of antibodies from the GBM indicates a strong affinity of antibodies to antigenic sites and that the removal of antibodies is intimately related to the slow metabolic turnover of the glomerular basement membrane. The findings help to explain some of the observations in human antibasement membrane antibody mediated disease of the Goodpasture's type. PMID- 2205513 TI - Retinoic acid induced differentiated neuroblastoma cells show increased expression of the beta A4 amyloid gene of Alzheimer's disease and an altered splicing pattern. AB - Retinoic acid (RA) induced differentiation of SH-SY5Y neuroblastoma cells is associated with more than a tenfold induction of total Alzheimer's disease beta A4 amyloid protein precursor (APP) mRNA as analyzed by Northern blot hybridisation. S1 nuclease protection experiments reveal that the splicing pattern of these differentiated cells is altered in favor of APP695 mRNA, coding for the shortest amyloidogenic beta A4 amyloid precursor protein. Induction of differentiation of SH-SY5Y cells with NGF leads to a fivefold increase of total APP mRNA without change in the splicing pattern. This suggests that RA but not NGF induces factor(s) which are responsible for an APP hnRNA splicing favoring APP695 mRNA. PMID- 2205514 TI - Determination of tRNA nucleotide residues directly interacting with proteins in the post- and pretranslocated ribosomal complexes. AB - Nucleotide residues of E. coli tRNA interacting directly with proteins in pre- and posttranslocated ribosomal complexes have been identified by analysis of photo-induced tRNA-protein cross-links. A9, G18, A26 and U59 residues of NAcPhePhe-tRNA, located in the Ab-site (pretranslocated complex) have been cross linked with proteins S10, L27, S7 and L2 respectively. In deacylated tRNA, located in the Pb-site, residues C17, G44, C56 and U60 have been cross-linked with proteins L2, L5, L27 and S9 respectively. The G44-L5 cross-link disappeared after translocation (NAc-PhePhe-tRNA located in the Pt-site). PMID- 2205515 TI - Interleukin-1 stimulates glucose transport in rat adipose cells. Evidence for receptor discrimination between IL-1 beta and IL-1 alpha. AB - The effect of interleukin 1 (IL-1) on glucose transport activity in isolated rat adipose cells was examined. IL-1 beta stimulated 3-O-methylglucose (3OMG) transport in a time and dose dependent manner. This effect appears to be due to increased maximal transport velocity (Vmax) of the carrier. Addition of insulin and IL-1 beta resulted in an additive stimulation of transport, suggesting different mechanisms. IL-1 alpha had no effect on glucose transport. Glu-4, a relatively inactive IL-1 beta analogue in most cells, stimulated glucose uptake in a time and dose dependent manner with kinetics indistinguishable from those of IL-1 beta. PMID- 2205516 TI - [Crystallo-chemical problems of dental enamel and new possibilities of in vitro remineralization]. AB - Incipient dental caries according to up-to-date concepts in dental research- means a demineralization without cavity formation. At this stage the carious process is reversible, and remineralization can occur in the presence of locally applied fluorides. In crystal chemical experiments, however, by treating natural apatites with lanthanides (Ce, La, Pr, Nd, Sm, Eu, Tb...Y, Sc) a more resistant complex could be developed. In this study extracted human molar teeth were kept for 60 days in Cerium (III)-nitrate solution, in order to investigate the incorporation of Ce3+ into human sound and carious enamel by light-microscopic-, and electron microprobe methods. Ce3+ was incorporated in sound enamel as well as into the incipient carious lesion, showing the histological characteristics of a remineralizing lesion. The mean values of the microprobe analysis data showed an increase in Ce3+ changing place with the Ca2+ the developing cerium-apatite being more hard and resistant from a mineralo-physical point of view. PMID- 2205517 TI - [Numerical anomalies of the dentition (main characteristics, therapy, prevention). Dental anomalies from the caseload of a district dentist, 9]. AB - The principal characteristics of numerical anomalies of the teeth are described: the occurrence, the incidence, the nomenclature. With healing such anomalies the cooperation of the oral surgeon, the prosthetic and the orthodontist is important. Methods of orthodontical, oral, surgical, and prosthetical treatment are described. Possibility of prevention, its significance and the necessity of examining such anomalies are mentioned. PMID- 2205518 TI - Glutaminolysis and glycolysis interactions in proliferant cells. PMID- 2205519 TI - Hereditary fructose intolerance. PMID- 2205520 TI - Interpretation of DNA vibrational spectra by normal coordinate analysis. AB - 1. In the following article we undertake a brief review of the most prominent DNA vibrational markers as observed experimentally by Raman and i.r. spectroscopies on polynucleotides and explain how a simplified valence force field can account for the evolution of the DNA vibrational spectra. 2. Our discussion made as a review of our previous investigations on the interpretation of DNA vibration modes, is based on some of the most characteristic and structure dependent DNA vibrational markers. PMID- 2205521 TI - The effect of triiodothyronine on glucose utilization in adipocytes from obese rats. AB - 1. In the presence of insulin, 10(-5) M 3,3',5-triiodothyronine (T3) treatment for 1/2 hr decreased fatty acid synthesis 35% only in adipocytes from lean rats, whereas at 10(-11) M through 10(-7) M T3 the obese adipocytes had nearly a 20% increase in fatty acid synthesis. 2. A 2 hr pretreatment of adipocytes with 10( 9) and 10(-7) M T3 decreased insulin-stimulated fatty acid synthesis by nearly 20% in both lean and obese adipocytes. 3. In the absence of insulin, the 2 hr pretreatment with 10(-9) M T3 resulted in a 45% increase in lean adipocyte fatty acid synthesis, though the obese adipocytes required at least 10(-7) M T3 for 2 hr to increase the non-insulin-stimulated fatty acid synthesis by 50%. 4. At 10( 9) M T3 concentrations non-insulin-stimulated fatty acid synthesis was increased by 200% in lean adipose tissue explants, but obese adipose explants were not significantly affected under these conditions. 5. The addition of 10(-9) M T3 plus insulin to the explant media decreased fatty acid synthesis by 35% in both the lean and obese tissues. 6. The results also imply that the low T3 status of the obese rat may be contributory to the elevated fatty acid synthesis observed in obese adipocytes. PMID- 2205522 TI - A semi-pharmaceutical approach for the preparation of an anti-IL2 receptor monoclonal antibody in the treatment of acute GvHD in a multicentric study. AB - A monoclonal antibody against the IL2-Receptor (B-B10) has been developed which inhibits activated T cells. Large batches of B-B10 have been purified from ascites and were checked for the absence of endotoxins, murine DNA and virus before being released for clinical use. Thirty-two patients with corticosteroid resistant acute Graft versus Host Disease have been treated with B-B10. No side effects were observed and 68% of the patients showed full response to treatment. PMID- 2205523 TI - Preclinical and clinical testing of radiolabelled monoclonal antibodies for immunoscintigraphy. AB - Immunoscintigraphy is a new method for in vivo diagnosis of diseases using monoclonal antibodies. Emphasis is placed on diagnosis of malignant tumors although the range of application includes a number of non-malignant diseases. To date, no European country has issued clear guidelines on the testing and registration of those monoclonal antibodies labelled with a radionuclide and used for diagnostic. This involves the risk of overregulation which would considerably reduce the applicability of the method. This holds particularly true since the complications initially anticipated with the use of such compounds did not occur. The conduct of immunoscintigraphy has evolved during the last few years. For reasons of applicability, but also and mainly for reasons of radiation hygiene, I 131 and finally also In-111 were abandoned as labelling nuclides and replaced by Tc-99m. The protein amount involved was reduced. Some false estimations, which were due to particularities or artifacts of the iodinated antibodies used at the beginning, had to be corrected: the representation of the liver in a scintigram is part of the physiological distribution of antibodies; and fragments of antibodies normally do not present the anticipated kinetic advantages. The clinical results obtained with colon carcinomas show that not only recurrencies and metastases, but also primary tumors can be detected with equally high sensitivity. In contrast, radioimmunotherapy does not yet seem as successful, at least against solid tumors. PMID- 2205524 TI - Between scientific application and therapy: the ethical consideration. AB - The development of bioscience and biotechnology during the last thirty years exerted a tremendous influence on medicine. New techniques have risen and new kinds of treatment have been and still are introduced. The theories concerning the pathogenesis and the causes of disease change, while new therapeutical drug become constantly available on the market. The way in which new technologies and drugs are introduced contains more and more an experimental phase in which animals and human beings are used to test the outcomes of research. As a rule, these experiments are performed in accordance with the Declaration of Helsinki (WMA, Helsinki 1964, Tokyo, 1975). The guidelines of this Declaration are concerned with the ethical aspects of those experiments which involve human subjects. Although the guidelines are intended to have a global import, it still remains a matter of fact that some of them are a matter of debate in several regions of the world. They seem to have a cultural background (e.g. respect for the individual) and bioscientists sometimes argue that fort this reason they have to be considered as non-scientific restrictions. On the basis of a general philosophical and ethical consideration, it will be argued in this paper that ethical guidelines belong to the heart of biomedicine and biology itself. It is the common interest of researchers, clinicians, patients and scientists to consider the ethical implications of research outcomes before it can be stated that any worthwhile knowledge is obtained. The implementation of monoclonal antibodies in clinical practice can be seen as a sample of this argument. PMID- 2205525 TI - Toxicological testing of monoclonal antibodies. AB - Toxicity studies with monoclonal antibodies for in vivo diagnostic or therapeutic administration must be designed case by case to take into account the intended use in humans and the type of structure (nude or coupled to immunotoxins or radionuclides). The design of experiments is influenced by the origin of the clone (murine or human with different problems of antigenicity) and the type of culture (ascites or fermentation with various kinds of possible contaminations). Therefore, routine animal tests must be supplemented by analytical procedures and assays of pharmacological quality control (pyrogenicity, abnormal toxicity). The antigenicity of these antibodies for experimental animals imposes restrictions concerning duration of experiments and extrapolation of the results to humans. Selection of appropriate species is difficult, they should have identical target cells if possible. Sometimes the choice is limited to non-human primates. Toxicological experiments should be based on pharmacokinetic studies. Formal tests on mutagenicity, teratogenicity and cancerogenicity are, in most cases, irrelevant. Antibody formation may make it impossible to carry out longer-term studies. PMID- 2205526 TI - Monoclonal antibodies for use in man: current regulatory situation in the Federal Republic of Germany. AB - The article addresses the requirement to be met for approval of monoclonal antibodies with special emphasis on products coupled with radionuclides and on principles for the conduct of clinical trials. According to the German Drug Law monoclonal antibodies are considered as being sera. Therefore, the Paul-Ehrlich Institut, Federal Office for Sera and Vaccines, is responsible for marketing authorizations. Sera and vaccines need a special manufacturing licence which is given by the competent authority of the Federal State. Batches of monoclonal antibodies can only be marketed if they have been released by the Paul-Ehrlich Institut; in connexion with batch control the importance of reference preparations is stressed. The standard requirements for the data to be submitted with the applications for marketing authorizations are in accordance with the EEC Council Directives and Notes for Guidance. For the testing of radioactive monoclonal antibodies in clinical trials, compliance with both the Drug Law and The German Radiation Protection Ordinance must be ensured. In addition to the authorizations required for non-labelled monoclonal antibody products, the use of radioactive substances in diagnosis and therapy requires an authorization by the competent Federal State authority. The main purpose of the planning and performance of clinical trials with new monoclonal antibody in diagnosis and therapy must be the comparison with established diagnostic tools and/or established medicinal products of known effect. PMID- 2205527 TI - Intravenous therapy with high doses of ranitidine and omeprazole in critically ill patients with bleeding peptic ulcerations of the upper intestinal tract: an open randomized controlled trial. AB - Thirty-nine critically ill patients with actively bleeding peptic ulcerations- Forrest Ib--in the stomach or duodenum were randomly allocated to intravenous therapy with 400 mg ranitidine per day or 80 mg omeprazole per day (120 mg on the 1st day) for 5 days. Successful therapy was proven by control endoscopy on day 6 if less than 2.5 liters of blood had to be transfused from the start of therapy to maintain a hemoglobin value of 10g/l or above. Treatment failure meant that more than 2.5 liters of blood were necessary to maintain a hemoglobin level above 10 g/l. Of 20 patients in the ranitidine group bleeding stopped in only 3 patients (15%). Of 17 patients who continued bleeding under ranitidine therapy the bleeding could be controlled in 13 patients after changing to omeprazole treatment. Of 19 patients in the omeprazole group bleeding stopped in 16 patients (84%). These results demonstrate that the significantly more effective reduction of acidity by omeprazole is promising for the therapy of bleeding peptic ulcerations and may reduce the need for invasive therapy or operation. PMID- 2205528 TI - Autoantibodies to the insulin receptor are infrequent findings in type 1 (insulin dependent) diabetes mellitus of recent onset. AB - To determine whether autoantibodies to the insulin receptor may represent markers of Type 1 (insulin-dependent) diabetes, the prevalence of such antibodies was investigated in sera of 60 newly diagnosed untreated Type 1 diabetic patients. A sensitive assay, based on enzyme linked immunosorbent assay has been set up which detects antibodies to the insulin receptor irrespective of their potentially inhibiting effect on insulin binding. Moreover, this method allows easy determination of the immunoglobulin class involved in the anti-receptor activity. Among the 60 sera examined, only one was found to contain anti-insulin receptor autoantibodies (IgG class). In view of our data, we conclude that autoantibodies to the insulin receptor are infrequent findings in Type 1 diabetes of recent onset. PMID- 2205529 TI - The spectrum of pancreatic exocrine and endocrine (beta-cell) function in tropical calcific pancreatitis. AB - Exocrine pancreatic marker (immunoreactive-trypsin) and endocrine Beta-cell function (plasma insulin and C-peptide during an oral glucose tolerance test) were studied in 40 subjects with tropical-calcific-pancreatitis [seven non diabetic, seven with impaired-glucose-tolerance and 26 diabetic (fibro-calculous pancreatic-diabetes)]. In non-diabetic and impaired-glucose-tolerance subjects there was evidence of active pancreatitis in some and exocrine function was partially preserved. Fibro-calculous-pancreatic-diabetic subjects showed severely diminished exocrine pancreatic function; none showed 'pancreatitic' elevation of immunoreactive-trypsin. Beta-cell function was preserved in non-diabetic and impaired-glucose-tolerance subjects; diabetic subjects showed variable Beta-cell function but it was severely diminished in more than 75%. Immunoreactive-trypsin and C-peptide were directly correlated (rs = 0.55, p less than 0.01). This cross sectional study demonstrates, for the first time, that the Beta-cell loss in tropical-calcific-pancreatitis is related to the exocrine loss. It suggests that diabetes in tropical-calcific-pancreatitis is either secondary to pancreatitis or that a common factor(s) acts simultaneously on both components. PMID- 2205530 TI - Isolation and characterisation of the crnA-niiA-niaD gene cluster for nitrate assimilation in Aspergillus nidulans. AB - Genomic clones containing the entire crnA-niiA-niaD gene cluster of Aspergillus nidulans have been isolated, and the structures of the niiA and niaD genes have been determined by nucleotide sequence analysis. This gene cluster is required for the assimilation of nitrate in A. nidulans, and the three genes encode a product required for nitrate uptake and the enzymes, nitrite reductase and nitrate reductase, respectively. The putative coding sequences, as deduced by comparison to cDNA clones of both niiA and niaD, are interrupted by multiple small introns, and the two genes are divergently transcribed. Identification and characterization of specific mRNAs involved in nitrate assimilation indicates that only monocistronic transcripts are involved, and that the approximate sizes of these transcripts are 1.6 kb, 3.4 kb and 2.8 kb for crnA, niiA and niaD, respectively. The results also indicate that control of niiA and niaD gene expression is mediated by the levels of mRNA accumulation, in response to the source of nitrogen in the growth medium. Two types of transcripts for niiA were observed. PMID- 2205531 TI - Microbody phosphoglycerate kinase of Trypanosoma brucei: expression and complementation in Escherichia coli. AB - In the primitive eukaryotic parasite, Trypanosoma brucei, most of the enzymes of glycolysis are located within microbody organelles called glycosomes. Proteins destined for the glycosome are synthesized on free ribosomes and post translationally translocated into the organelle. The gene, gPGK, encoding the glycosomal isozyme of phosphoglycerate kinase (gPGK), was cloned adjacent to a T7 promoter and cotransformed with a plasmid encoding T7 RNA polymerase into Escherichia coli Pgk-cells. Functional complementation occurred, but only after the creation of a ribosome-binding site by mutagenesis. This represents the first example of complementation of an E. coli mutant with a gene encoding a microbody protein. Enzymatically active recombinant gPGK was purified to near homogeneity by ion exchange chromatography from highly expressing E. coli. The recombinant protein will aid in studies of glycosomal biogenesis. PMID- 2205532 TI - Efficient secretion of human parathyroid hormone by Saccharomyces cerevisiae. AB - A cDNA encoding mature human parathyroid hormone (hPTH) was expressed in Saccharomyces cerevisiae, after fusion to the prepro region of yeast mating factor alpha (MF alpha). Radioimmunoassay showed high levels of hPTH immunoreactive material in the growth medium (up to 10 micrograms/ml). More than 95% of the immunoreactive material was found extracellularly as multiple forms of hormone peptides. Three internal cleavage sites were identified in the hPTH molecule. The major cleavage site, after a pair of basic amino acids (aa) (Arg25Lys26 decreases Lys27), resembles that recognized by the KEX2 gene product on which the MF alpha expression-secretion system depends. The use of a protease deficient yeast strain and the addition of high concentrations of aa to the growth medium, however, not only changed the peptide pattern, but also resulted in a significant increase in the yield of intact hPTH (1-84) (more than 20% of the total amount of immunoreactive material). The secreted hPTH (1-84) migrates like a hPTH standard in two different gel-electrophoretic systems, co-elutes with standard hPTH on reverse-phase high-performance liquid chromatography, reacts with two hPTH antibodies raised against different parts of the peptide, has a correct N-terminal aa sequence, and has full biological activity in a hormone sensitive osteoblast adenylate cyclase assay. PMID- 2205533 TI - Primary structure of the putative human oncogene, pim-1. AB - A full-length (6.1-kb) human genomic pim-1 gene, together with its immediate 5' upstream promoter sequence (Ppim) was isolated and sequenced. The human pim-1 gene shares an overall nucleotide (nt) sequence identity of 53% with the previously reported murine pim-1 gene. It consists of six exons and five introns and contains a protein-coding region that is identical in nt sequence to a full length human pim-1 cDNA. The gene codes for a predicted Pim-1 protein of 313 amino acids (aa) with an Mr of 35,690 and a pI of 5.7. The deduced aa sequence of the human Pim-1 has 94% identity with the murine Pim-1 whereas the nt sequences of the two genes are 88% identical. All of the conserved aa residues of the mouse pim-1 gene, which are homologous to known protein kinases are conserved in the predicted human protein. The human Ppim region is very G + C-rich (69%) and shares greater than 80% identity with the murine Ppim. The Ppim has no TATA- or CAAT-box sequences but does contain a number of nt sequences similar to the putative binding sites of several presumptive transcription factors. PMID- 2205535 TI - Cloning and nucleotide sequence of the CDC23 gene of Saccharomyces cerevisiae. AB - As a preliminary step for studying the function and intracellular behavior of the product of the CDC23 gene, a cell cycle gene of Saccharomyces cerevisiae, we cloned the CDC23 gene and determined its nucleotide (nt) sequence. The nt sequence contains an open reading frame (ORF) of 1878 nt coding for a protein of 626 amino acids (aa). The CDC23 gene is expressed as a 2.4- to 2.5-kb major transcript. The putative protein product of the CDC23 gene has a potential Ca2(+) binding site near its N terminus, and has four contiguous repeats of a consensus sequence consisting of 34 aa near its C terminus. Regions that can be regarded as consisting of repeats of the same consensus sequence were found in the published aa sequences of the products of three other yeast genes. PMID- 2205534 TI - Mutations within the replicon of the IncN plasmid pCU1 that affect its Escherichia coli polA-independence but not its autonomous replication ability. AB - The minimal replicon of the incompatibility N group plasmid pCU1 is contained within a 2-kb DNA region of the plasmid. The ability of this region and of the deletion derivatives thereof, that are capable of autonomous maintenance, to direct polypeptide synthesis was examined. Two proteins of 27 and 5.5 kDa are encoded by the minimal replicon. Polypeptide chain-terminating mutations within the predicted open reading frame for the 27-kDa polypeptide abolished the synthesis of this polypeptide and also the Escherichia coli polA-independence phenotype of the pCU1 replicon. However, these mutations did not affect the autonomous replication ability of the pCU1 replicon in wild-type E. coli and the expression of incompatibility towards the parental plasmid. PMID- 2205536 TI - The 5'-leader sequence of tobacco mosaic virus RNA mediates initiation-factor-4E independent, but still initiation-factor-4A-dependent translation in yeast extracts. AB - Messenger RNAs encoding chloramphenicol acetyltransferase (CAT) with or without the 5'-leader sequence of tobacco mosaic virus (TMV) RNA were synthesized in vitro and translated in Saccharomyces cerevisiae extracts dependent on eukaryotic initiation factors eIF-4E or eIF-4A. The 5'-leader sequence of TMV RNA renders translation of CAT mRNA eIF-4E-independent but still 4A-dependent. PMID- 2205537 TI - Expression of the gene encoding firefly luciferase in insect cells using a baculovirus vector. AB - A cDNA encoding the firefly luciferase [Photinus luciferin: oxygen 4 oxidoreductase (decarboxylating, ATP-hydrolyzing), EC 1.13.12.7] was cloned downstream from the polyhedrin gene promoter of Autographa californica nuclear polyhedrosis virus and expressed in Spodoptera frugiperda clone-9 cells. Synthesis of luciferase (Luc) was accurately measured in insect cells growing in a 96-well plate, by a simple, rapid, nonradioactive, inexpensive and sensitive method based on fogging of x-ray film. Luc was produced in a coordinate fashion during virus infection. The Luc synthesized in insect cells was not secreted into the medium but was contained within the cell. Our findings suggest that Luc can be used as a superior reporter enzyme for molecular genetic analyses of baculovirus regulatory signals involved in high level expression of foreign genes, protein processing, targeting and stability in insect cells. PMID- 2205538 TI - The methane monooxygenase gene cluster of Methylococcus capsulatus (Bath). AB - Methane is oxidised to methanol in methanotrophic bacteria by the enzyme methane monooxygenase (MMO). Methylococcus capsulatus (Bath) produces a soluble MMO which oxidises a range of aliphatic and aromatic compounds with potential for commercial exploitation. This multicomponent enzyme has been extensively characterised and biochemical data have been used to identify a 12-kb fragment of Methylococcus DNA carrying the structural genes mmoY and mmoZ, coding for the beta- and gamma-subunits of MMO component A, the methane-binding protein. We now report the complete nucleotide (nt) sequence of mmoX, the gene encoding the alpha subunit of component A which is found to be 5' to mmoY and mmoZ. We also report the complete nt sequence of mmoC which encodes component C, the iron-sulfur flavoprotein of MMO, the N terminus of which is significantly homologous with spinach ferredoxin. The mmo structural genes are clustered within a 7-kb region and are closely linked to two small open reading frames of unknown function. PMID- 2205539 TI - Expression of a foreign KmR gene in linear killer DNA plasmids in yeast. AB - The killer plasmids of the yeast Kluyveromyces lactis, pGKL1 and 2 (k1 and k2 for short), are linear double-stranded DNAs. The expression of genes of these plasmids is thought to depend on their own transcription system. Cloning the plasmid genes in conventional circular vectors is therefore not suitable for transcriptional studies, because such vectors use the host nuclear transcription system. In vitro modification of the linear plasmid genomes in order to introduce transcription reporter genes has been difficult because the structure of the plasmids, with covalently bound terminal proteins, does not allow their manipulation in vitro and amplification in Escherichia coli. We introduced the kanamycin/G418 resistance gene, KmR, into the k1 plasmid in vivo, by transforming the yeast with the linearized KmR gene bordered with short k1 sequences (part of the region encoding the toxin) to allow homologous recombination with the resident k1. In the linear recombinants obtained, however, the KmR was not expressed, while it was expressed if carried on circularized plasmids. By replacing the native promoter of KmR by the ORF1 promoter from k1, the KmR gene could be expressed in linear recombinants and conferred on the host a high level of resistance to the drug. All the linear recombinant plasmids were extremely stable under nonselective conditions. As a rare event, the integration of KmR produced a palindromic rearrangement of the k1 plasmid. PMID- 2205540 TI - Genetic diversity in the major merozoite surface antigen of Plasmodium falciparum: high prevalence of a third polymorphic form detected in strains derived from malaria patients. AB - We studied the diversity of the polymorphic 195-kDa antigen (p190) of Plasmodium from infected individuals. Genomic parasite DNA was extracted from the blood of 30 donors from different endemic areas of Brazil. The 5' region, encoding the polymorphic N-terminal part of p190 was analysed following polymerase chain reaction (PCR). Multiple infections of genetically distinct parasites could be detected within infected malaria patients. Sequence analysis and oligodeoxyribonucleotide typing of the PCR products demonstrated the prevalence of a third polymorphic form of p190. PMID- 2205541 TI - Cloning and expression in Escherichia coli of a hypoxanthine-guanine phosphoribosyltransferase-encoding cDNA from Plasmodium falciparum. AB - The enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) of Plasmodium falciparum plays a key role in the salvage of preformed purine nucleotides from parasite-infected erythrocytes. Since P. falciparum cannot synthesize purines de novo, development of inhibitors specific for the parasite HGPRT should be an effective method of chemotherapy. To provide sufficient amounts of HGPRT for biochemical and crystallographic analysis, we have isolated the P. falciparum HPRT cDNA sequence and expressed it in an Escherichia coli strain deficient for both de novo purine synthesis and guanine utilization (strain GP120). GP120 cells containing the P. falciparum HPRT plasmid vector (pRD500), when grown in the presence of isopropyl-beta-D-thiogalactopyranoside (IPTG) which induces the tac promoter of the expression vector, produce a novel protein of 26 kDa, which is in agreement with the predicted Mr deduced from the HPRT cDNA open reading frame. In addition, we have demonstrated significant HGPRT activity in cell-free extracts of GP120[pRD500] cultures grown in minimal medium containing xanthine, as the sole source of purines, and IPTG. PMID- 2205542 TI - Intra- and intermolecular site-specific recombination in plant cells mediated by bacteriophage P1 recombinase. AB - A site-specific recombination system has many potential uses for rearranging genetic material in higher eukaryotic cells: for example, the control of gene expression by deletion or inversion of DNA segments, the clustering of transgenic constructs via site-specific integration, and the generation of chromosomal translocations. In this report, we describe a first step towards the application of a site-specific recombination system in plant cells. By use of a transient assay, we demonstrate that the bacteriophage P1 cre gene can be expressed as a functional recombinase in tobacco cells. Upon expression in tobacco protoplasts, Cre recognizes its target sites, lox, and mediates reciprocal genetic crossovers at these sites. When the lox sites are present in cis to one another, and arranged in either direct or inverted orientations, we detect Cre/lox-specific deletion and inversion events, respectively. The placement of lox sites in trans resulted in the co-integration of the substrates by Cre-mediated intermolecular recombination. These results indicate that the Cre/lox site-specific recombination system might be further developed as an additional tool for manipulating DNA in plant cells. Applications relevant to the genetic engineering of higher plants are discussed. PMID- 2205543 TI - Differential gene expression mediated by late, very late and hybrid baculovirus promoters. AB - A series of recombinant viruses was constructed to study the regulation of expression from the promoter (Pcap) for the major capsid-protein-encoding gene (vp39) of the baculovirus, Autographa californica nuclear polyhedrosis virus. Each virus of this series contains the cat reporter gene under the control of Pcap or portions thereof. Pcap regulation of cat was determined at the RNA and enzyme activity levels, and was compared to cat gene expression driven by Ppolh, the promoter of the polyhedrin gene (polh). Although optimum expression was achieved with a 464-bp region, which included all three Pcap transcription start points (tsp), a 99-bp segment of Pcap containing a single tsp was sufficient to direct late cat expression. Ppolh and Pcap-mediated regulation differed temporally; Pcap-cat constructs were expressed at 12 h post-infection (p.i.) and continued through 48 h p.i., whereas Ppolh-cat were not expressed at 12 h, but were initiated around 18 h p.i. and underwent a burst of expression between 24 and 48 h p.i. A recombinant virus carrying a hybrid and polh promoter (Pcappolh) was also constructed and studied; Pcappolh contained the two distal tsp of Pcap and a proximal tsp of Ppolh. Pcappolh exhibited both 'late' and 'very late' regulation; the distal tsp were regulated as late sites and the proximal tsp was regulated primarily as a very late site although it also showed a weak late response. Hybrid late/very late promoters should prove useful in optimizing foreign gene expression using baculovirus vectors. PMID- 2205544 TI - The ophthalmic rod: a new ophthalmic drug delivery system I. AB - The ophthalmic rod (OR) is a new drug delivery system, intended as an alternative to conventional therapy in ophthalmology. The rod is made of a nontoxic plastic. It is dipped into a drug solution which after drying forms a thin homogeneous coating. The OR is then packed and sterilized by gamma radiation. The effects of radiation on the contents of the drugs were studied using IR, UV, and thin-layer chromatography (TLC). Sterility, dose variation, and simulated drug delivery in vitro were tested. Pure drugs were used; no preservatives were included. To deliver the drug, the tip of the rod is introduced into the conjunctival sac and rubbed against the palpebral conjunctiva of the lower lid. ORs with tropicamide, oxybuprocaine HCl, pilocarpine HCl, and fluorescein sodium were used. The behavior of the drugs administered by this system was compared with eyedrops. Results of trials with three drugs, i.e., tropicamide, oxybuprocaine HCl, and fluorescein sodium on ORs applied to the eyes of humans and those of the rabbit are discussed. PMID- 2205545 TI - The ophthalmic rod--a new drug-delivery system II. AB - The ophthalmic rod (OR) is a new ophthalmic drug-delivery system. The rod is made of nontoxic plastic. The active substance is deposited as a thin film on the end of the rod. To deliver the drug, the tip of the rod is introduced into the conjunctival sac and rubbed against the palpebral conjunctiva of the lower lid. The OR is a single-dose sterile applicator. By using the OR the problems of preservation and sterility of eyedrops are eliminated, and the risk of cross infection is avoided. This was an open uncontrolled study. Clonidine ORs were used by 15 patients with glaucoma for 12 days. Fluorescein ORs were used for tonometry and to check the safetness of using the ORs. Patients with dry eyes or scotoma were excluded from the study. The clonidine film remaining on the ORs after delivery was quantitatively analyzed. A dose of 20 micrograms clonidine rod, three ORs/day, was sufficient to keep the ocular pressure under control. The fluorescin ORs, 30 micrograms/rod, were satisfactory for coloring the cornea. On the last day (12th) no clinically apparent side effects were observed. Subjectively, the patients were satisfied with the OR method of application, as an alternative to eyedrops. PMID- 2205546 TI - Regenerative and proliferative capacity of adult human retinal cells in vitro. AB - The present work was undertaken (a) to determine whether adult human retinal neurons possess the ability to survive and regrow neurites in organ cultures and (b) to investigate the maintenance and proliferative activity of retinal glial cells in vitro. Using material from retinae obtained from human eyes postenucleation we established in vitro organ cultures of retinal pieces in a chemically defined, serum-free medium, previously developed for culturing adult rat and chick retinae. The time course of glial cell migration and of neurite extension was compared with that of adult rat and chick retinae which have been extensively investigated in our laboratory. It appeared from four explanted retinae that the human retinal cells survive for up to 4 weeks in culture and exhibit their typical morphologies. Immunohistochemical investigation of the migrating cells revealed that both astrocytes and Muller-like cells exhibit their typical morphologies in vitro. In explants obtained from a retina 30 years after very traumatic violence to the eye cup, the glial cells but not the neurons extended lengthy fibers. In the explants obtained from a retina about 2 months after traumatic optic nerve injury and subsequent ocular complications, several lengthy fibres were extended from the transplant's edge. They could be labeled with neurofilament antibodies but not with glial fibrillary acidic protein antibodies, indicating their neuronal origin. The results suggest that some injured human retinal neurons respond to exposure to growth-permissive substrates by regeneration of their neurites. Although some morphological features of the fibers suggest that they originate from ganglion cells in the retinal explants, definitive proof of this is not yet available. PMID- 2205547 TI - Assessment of pain in newborns and children. PMID- 2205548 TI - Dietary headaches through the centuries. PMID- 2205549 TI - Role blurring and the hospital social worker's search for a clear domain. AB - Hospital social workers strive to define their professional domain to avoid blurring their roles with those of other health care professionals. Hospital social workers are concerned with gaining and retaining recognition by patients, families, and colleagues of their distinct professional contribution. This article reviews the evolution of social workers' roles and functions in hospitals and reflects on the frequently noted discrepancy between self-ascribed roles and those conceded to social workers by other health care professionals. Issues of collaboration in the context of interdisciplinary activity are considered, and the impact of overlapping roles on social work practice is assessed. The value and drawbacks of role ambiguity are discussed, and strategies for role clarification and development of a better-defined domain for social workers in hospitals are recommended. PMID- 2205550 TI - The impoverishment of native Hawaiians and the social work challenge. AB - Native Hawaiians, the people indigenous to the Hawaiian Islands, are impoverished in quality of life. Only recently has the myth that native Hawaiians are a carefree people living in a tropical paradise been dispelled. The number of health and mental health problems confronting native Hawaiians is alarming; their general health status is far below that of other U.S. population groups. It is urgent that social workers begin to examine the unique circumstances of native Hawaiians and encourage professional support for the planning of culturally appropriate services for this population. PMID- 2205551 TI - [The treatment of tinnitus]. AB - Tinnitus does not present a uniform clinical picture but may represent a symptom of local or systemic disease. If it persists after treatment of the underlying disease or condition, symptomatic treatment should be instituted. Selection criteria for the therapeutic strategy are provided by a classification on the basis of the following points: 1. can be masked by a sound, 2. response to parenteral lidocaine. For clinical purposes, these forms of tinnitus can be considered cochlear or neural, respectively. The cochlear form is best treated by physical means (tinnitus masking), peripheral-neural tinnitus by antiarrhythmic drugs. Successful management requires a particular doctor/patient relationship in which the patient needs above-average time and attention, which the physician cannot delegate to others. PMID- 2205552 TI - [The development of an aerobic intestinal microflora in newborn infants]. AB - The microbial colonization of the intestinal tract was studied in 60 newborn babies from three hospitals, with special regard to the typical hospital "problem" strains. Escherichia coli was the predominant initial colonizing species. Opportunistic pathogens were repeatedly detected. Some 30% of E. coli strains showed beta-hemolysis. Distinct differences between the three clinics were noted with respect to the detection frequency of the species isolated, hemolytic bacteria, the predominating E. coli strains, the occurrence of Candida albicans, and the time course of colonization of the gut by E coli. The microbial environment of the respective neonatal unit has a great influence on the initial intestinal colonization by aerobic microorganisms. PMID- 2205553 TI - [Giant hepatic cyst effectively treated by transdermal transhepatic ethanol injection therapy. A case report]. AB - Giant hepatic cysts were effectively treated by transhepatic ethanol injection therapy. A 68-year-old male and a 70-year-old female were admitted to Kyushu University Hospital because of epigastric fullness. Ultrasound and CT examination disclosed a giant cyst in the left lobe of the liver of both patients. 99% ethanol of about a quarter of volume of the cysts were infused through catheter transdermal. After retaining for 15 minutes the ethanol was discarded and this procedure repeated twice. The cysts have been keeping a minimum size and the patients are free from symptoms for over one year. PMID- 2205554 TI - Effects of a fructose-enriched diet on plasma insulin and triglyceride concentration in SHR and WKY rats. AB - Significant increases (P less than 0.001) in plasma insulin and triglyceride concentrations and in blood pressure were seen when SHR and WKY rats ate a fructose-enriched diet for 14 days. However, all of the changes were significantly accentuated (P less than 0.02-0.001) in SHR rats. Specifically the increment in plasma insulin concentration following the fructose-enriched diet was 42 +/- 4 microU/ml in SHR as compared to 25 +/- 4 microU/ml in WKY rats (P less than 0.001). Plasma triglyceride concentrations also increased to a greater degree in response to fructose in SHR rats (260 +/- 24 vs. 136 +/- 20 mg/dl, P less than 0.001). Finally, the fructose-induced increase in blood pressure of 29 +/- 4 mm of Hg in SHR rats was greater (P less than 0.02) than that seen in WKY rats (19 +/- 2 mm of Hg). There was no change in plasma glucose concentration in response to the fructose diet. WKY rats gained more weight than did the SHR rats. Thus, although plasma triglyceride and insulin concentration and blood pressure increased when either WKY or SHR rats consumed a fructose enriched diet, the magnitude of these changes was greater in SHR rats. PMID- 2205555 TI - Differences in glucose transport rates between perfused and in vitro incubated muscles. AB - In vitro incubated muscles are a convenient preparation for glucose transport studies, but it is not known how closely they reflect the in vivo condition. Perfused muscle preparations more closely resemble the in vivo condition, and thus to validate the use of in vitro incubated muscles, we have compared glucose transport rates in the two preparations. 3-O-Methylglucose transport rates in incubated soleus (SOL) and extensor digitorum longus (EDL) muscle strips were compared to transport rates obtained in SOL and EDL muscles removed from perfused hindquarters. Male Sprague-Dawley rats (250 g) were used for both procedures. SOL muscles showed an average 25% higher transport rate than EDL muscles at all insulin concentrations examined (0-100 nM) in the perfused system. This difference was diminished in the incubated muscles, SOL being 15% greater than EDL, but the relationship between the two muscles was maintained. Basal transport was lower and maximal transport was higher in the perfused muscles compared to the incubated muscles. This resulted in significantly higher fold stimulation in the perfused vs. incubated muscles (15 vs. 2.5 in the SOL, and 9.8 vs. 2.3 in the EDL). We conclude that in vitro muscle preparations may be convenient for showing relative differences between experimental treatments, but absolute transport rates and insulin stimulation must be interpreted with caution. PMID- 2205556 TI - Both macrophages and endothelial cells of the human hepatic sinusoid express the CD4 molecule, a receptor for the human immunodeficiency virus. AB - Hepatic sinusoidal lesions, including peliosis hepatis and sinusoidal dilatation, are frequently observed during human immunodeficiency virus infection. It has been proposed that human immunodeficiency virus itself plays a role in their pathogenesis. To test this hypothesis, we attempted to determine whether liver sinusoidal cells express the CD4 molecule, which behaves as a membrane receptor mediating the binding of human immunodeficiency virus to its target cells. For this purpose, three monoclonal antibodies-OKT4, OKT4a and anti-Leu3a + 3b, binding to different epitopes of the CD4 molecule-were used. All antibodies tested had the same tissue reactivity. On light microscopy, they reacted with most sinusoidal macrophages and in addition gave a continuous labeling of the sinusoidal lining suggestive of endothelial cell reactivity. On ultrastructural examination, the plasma membranes of both sinusoidal macrophages and endothelial cells were labeled. The reactive antigen was characterized by immunoblotting of liver homogenates. A unique band was detected, corresponding to an antigen with an apparent molecular weight of 54,000 Da, comparable to that reported for the CD4 molecule expressed on lymphocytes and monocytes. Therefore combination of structural and immunochemical data makes it possible to assess that both endothelial cells and macrophages of the hepatic sinusoid express the CD4 molecule. Consequently, both cell types constitute putative targets for human immunodeficiency virus and/or human immunodeficiency virus-related lesions. They may be involved in the pathogenesis of liver sinusoidal lesions observed in human immunodeficiency virus infection and may constitute an unsuspected reservoir of the virus. PMID- 2205557 TI - Mitochondrial structure and function in CCl4-induced cirrhosis in the rat. AB - To investigate whether the impairment of mitochondrial function in cirrhosis is due to a reduction in liver cell mass or whether mitochondrial function is altered specifically, we analyzed mitochondrial volume and surface density of mitochondrial membranes in control and cirrhotic rats by stereological means. Cirrhosis was induced by long-term exposure to phenobarbital and CCl4. Hepatocellular and mitochondrial volumes were reduced to a similar extent, by 39% and 40%, respectively, in cirrhotic animals (p less than 0.01). Thus the fraction of hepatocytes occupied by mitochondria did not differ between the two groups. Both total outer (31 +/- 3 vs. 19 +/- 6 m2; p less than 0.01) and inner (87 +/- 24 vs. 45 +/- 12 m2; p less than 0.01) mitochondrial membranes were significantly reduced. Membrane surface was normal per unit of mitochondrial volume, however, suggesting intact mitochondrial structure. Matrix and outer membrane enzyme activities expressed per compartment did not differ between control and cirrhotic animals. Inner membrane, in contrast, had an increased enzyme content per unit area both for cytochrome oxidase (10.3 +/- 2.9 vs. 13.0 +/- 1.6; p less than 0.05) and ATPase (13.7 +/- 1.4 vs. 21.2 +/- 2.9; p less than 0.01). Basal oxygen consumption measured in the perfused liver in situ was significantly reduced in cirrhotic livers (1.6 +/- 0.1 vs. 1.1 +/- 0.4 mumol/min-1/gm-1) but was unchanged when expressed per square meter of inner membrane. Our results demonstrate that impaired mitochondrial function is mainly due to loss of hepatocellular mass. Increased enzyme activity per unit surface area of inner mitochondrial membrane may be important to maintain mitochondrial function of the cirrhotic liver. PMID- 2205558 TI - Insights into the pathogenesis of alcoholic liver necrosis and fibrosis: status report. AB - The use of the Tsukamoto-French rat model of alcoholic liver disease facilitated pathological, physiological, biochemical and cell biological experiments that examined the validity of some of the existing hypotheses for pathogenesis of alcoholic liver necrosis and fibrosis. Results obtained to date strongly support the contribution of centrilobular hypoxia as a pathogenetic mechanism of alcoholic liver necrosis. The enhanced hepatic lipid peroxidation was not evident at the early stage of ethanol-induced liver necrosis but could be demonstrated at the late stage when the liver damage progressed to liver fibrosis. This suggests that the lipid peroxidation may not be an important mechanism of alcoholic liver necrosis but may be an initiation factor for liver fibrogenesis as recently proposed by others (88). The high-fat diet appears to have promoting effects on both induction of alcoholic liver necrosis and stimulation of liver fibrogenesis. The former may be related to the induction of MEOS by the high-fat diet and consequent centrilobular hypoxia caused by inadequately compensated hepatic overuse of oxygen. The latter can be mediated through sensitization of Ito cells by a high-fat diet. We propose that Kupffer cell-derived TGF beta is, at least in part, responsible for some of phenotypical changes of Ito cells associated with their activation. Our model provides maximal experimental control and induces the discrete stages of alcoholic liver injury that can be reproduced with its pathological evolution telescoped into a short time. Because of these features, replication of the experimental conditions in different laboratories is possible so that results can be validly compared through precise standardization of the experimental protocols. This model requires some training in implantation and maintenance of the gastric catheter. However, the training can be easily attained by anyone who has experience in animal surgery. Another requirement is the initial fund to acquire infusion devices and metabolism cages. Once this equipment is purchased, however, the maintenance cost is low. Even if the initial expenses are included, the cost per animal is relatively inexpensive when compared with the cost involved in the use of larger animals such as baboons or pigs. Since administration of diet and ethanol (or isocaloric glucose solution) is precisely controlled by infusion pumps, this system makes unnecessary the measurement of diet consumption that has to be done daily for each animal with other methods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2205560 TI - Corticosteroid therapy of alcoholic hepatitis: how many studies will it take? PMID- 2205559 TI - Acetaldehyde and alcoholic fibrogenesis: fuel to the fire, but not the spark. PMID- 2205561 TI - Sociological investigations of mental illness: a review. AB - Contemporary sociological research has expanded knowledge about how the label of mental illness affects individuals and about how patients' and psychiatrists' social characteristics affect the assessment and treatment of mental disorders. The authors review the recent sociological research dealing with the effect of extrapsychiatric factors such as social class, race, gender, marital status, and age on the development, diagnosis, and treatment of mental illness. They also examine sociological studies of the social role of the state hospital, the consequences of deinstitutionalization for chronic mentally ill patients, and the relationship of mental illness and homelessness. Studies that examine the social aspects of psychiatric practice, including the objectivity of psychiatric diagnosis, are also reviewed. PMID- 2205562 TI - Use of health professionals poses payment, authority conflicts. AB - The role of the nonphysician health professional is expanding. Health care sources say several factors are fueling this trend, including the familiar needs to reduce health care costs and improve access to care. And some legislators are planning bills to support this trend. In addition, some health care executives are also finding new roles for allied health professionals in cooperation with medical staff members. PMID- 2205563 TI - Retiring CEO: satisfy needs of customers, especially MDs. PMID- 2205564 TI - Exec promotes cost-effective patient care. PMID- 2205565 TI - RN clears path for nurse-MD collaboration. PMID- 2205566 TI - The Indian Health Program: the first 200 years. PMID- 2205567 TI - Imprint. 1990. Publishers directory. Resource books for nursing students. PMID- 2205568 TI - Effect of pH stress on lipid composition of Saccharomyces cerevisiae. AB - Total lipids (% dry weight basis) of S. cerevisiae increased when pH of the growth medium was altered. Phospholipid content increased when the yeast was grown at a pH higher than its optimal (pH 6). Sterol content was not affected much. Sterol:phospholipid ratio was not affected by pH of the medium. Phosphatidylcholine content of S. cerevisiae was inversely related to pH of its growth medium. Glycolipids were more when the yeast was grown at pH 9. Fatty acids of S. cerevisiae grown at pH 3 were more saturated which makes the membranes less fluid. PMID- 2205569 TI - Fetal ponderal index in predicting growth retardation. AB - Fetal ponderal indices were calculated by ultrasound examination and compared with the neonatal ponderal indices in 154 pregnancies. No significant difference was found between the prenatal and postnatal values of weight, length and ponderal indices of the entire sample as well as in babies with intrauterine growth retardation (IUGR). The fetal ponderal index had a sensitivity and specificity of 56.7 and 84.6 per cent respectively. These data suggest that fetal ponderal index could be used to rule out IUGR with reasonable accuracy (negative predictive value: 86%). PMID- 2205570 TI - Effect of a Siddha drug (Vatharasavangam) on insulin release from isolated pancreatic islets in rabbits. AB - The Siddha drug--Vatharasavangam (VRV) was studied in rabbits for its hypoglycemic activity. The insulin level in alloxan-induced hyperglycemic animals increased significantly after treatment with VRV. The insulin release from the isolated islets to glucose stimulus and acid phosphatase activity in islets as an index to islet function were measured. The insulin released from the islets in hyperglycemic rabbits decreased from 70 microU/ml (control) to 32 microU/ml to low glucose stimulus. VRV-treated rabbits showed a significant increase in the insulin released from the islet cells (65 microU/ml) to the low glucose stimulus. Similarly, a significant increase of insulin secretion was observed for high glucose stimulus after 30 min in VRV treated rabbits (100 microU/ml), when compared to hyperglycemic rabbits (70 microU/ml). The islet cell acid phosphatase activity in the hyperglycemic rabbits increased significantly after VRV treatment. These findings suggest that VRV acts by stimulating beta-cells to secrete insulin to the glucose signal and improves blood glucose homeostasis. PMID- 2205571 TI - Tracheal extubation under intravenous xylocaine. AB - The quality of extubation and circulatory changes during extubation of the trachea with or without prior xylocaine (1 mg/kg iv) were observed in 30 patients having CAD or 2 or more cardiac risk factors. 73.33 per cent of the patients receiving xylocaine had smooth extubation (grade I) in contrast to only 46.66 per cent in the control group. Also, in patients in the xylocaine group, the circulatory changes were statistically insignificant as compared to highly significant rise in rate pressure product in the control group. PMID- 2205572 TI - Arthroscopy in acute knee injuries: a prospective controlled trial. AB - Eighty-two patients took part in a prospective trial to assess the need and timing for arthroscopy in acute knee injuries. Patients with a suspected ligament injury, a suspected meniscal tear, or a haemarthrosis in the absence of fracture were included in the trial. Patients were entered randomly into two groups. In group I early arthroscopy was performed (within 48 h), in group II arthroscopy was performed within 21 days, but only when it was felt to be clinically indicated. Patients were assessed using the OAK knee score 1 year after the injury. There was no difference in the final result between the two groups. Early arthroscopy (within 48 h) showed no beneficial effect when compared with delayed arthroscopy (3 to 21 days after the injury). Indeed, an important diagnosis was missed at early arthroscopy in three cases, which led to delay in subsequent diagnosis and treatment. Arthroscopy raised the diagnostic accuracy from 61 per cent to 93 per cent. Considerable morbidity arises as a result of acute knee injuries. Clinical judgment will correctly define the need for arthroscopy in most cases at the time of injury, and arthroscopy is not necessary in all cases of acute haemarthrosis. PMID- 2205573 TI - Do all abdominal bullets need to be removed? PMID- 2205574 TI - Cloning and complete nucleotide sequence of the gene for the main component of hemagglutinin produced by Clostridium botulinum type C. AB - In Clostridium botulinum types C and D, phage conversion to toxin and hemagglutinin (HA) production has been reported. DNA was extracted from a converting type C Stockholm phage, c-st, and a fragment (7.8 kilobase pairs) coding for the parts of both toxin and HA was cloned. The gene for HA was recloned, and the complete nucleotide sequence was determined. The molecular mass of this gene product was 33 kilodaltons, and it showed HA activity. The HA preparation partially purified from a type C Stockholm culture demonstrated two major bands (33 and 53 kilodaltons) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with or without reducing agent. The amino acid sequence of the N terminus of the 33-kilodalton component of the native HA preparation, which was determined by a direct protein microsequencing procedure, was identical to that deduced from the nucleotide sequence of cloned HA gene. These data indicate that the cloned gene product (33 kilodaltons) is an important component of HA. PMID- 2205575 TI - Pathophysiologic glucocorticoid elevations promote bacterial translocation after thermal injury. AB - Thermal injury results in transient elevations of plasma glucocorticoids and promotes translocation of bacteria from the gut to the mesenteric lymph nodes (MLN) in rats. Translocated organisms are quickly cleared following uncomplicated thermal injury. However, subsequent burn wound infection, in temporal association with sustained pathophysiologic elevations of plasma corticosterone, results in the continued presence of enteric bacteria in the MLN. To study the role of sustained pathophysiologic steroid elevations in the mediation of this prolonged bacterial translocation, Wistar rats were randomly placed in groups receiving one of the following: (i) a 30% total body surface area scald injury with placement of a subcutaneous corticosterone pellet, (ii) a 30% total body surface area scald and a sham pellet implantation, (iii) a sham burn and a corticosterone pellet implantation, or (iv) a sham burn and a sham pellet implantation. The animals were sacrificed on days 1 and 4 after injury, and cultures of the MLN, as well as the liver and spleen, were taken. Implantation of corticosterone pellets resulted in sustained elevations of plasma corticosterone compared with controls not receiving corticosterone pellets, similar to results seen in association with injury and infection. These pathophysiologic elevations were associated with the prolonged presence of organisms in the MLN (90% of burned rats with implanted corticosterone pellets versus 25% of rats with uncomplicated burns on postburn day 4; P less than 0.01), but only in the presence of burn injury. Pathophysiologic glucocorticoid elevations did not lead to progression of translocation to the viscera or blood. Thus, the pathophysiologic glucocorticoid response contributes to the translocation of enteric bacteria and their prolonged presence in the MLN after systemic injury. PMID- 2205576 TI - Production of tumor necrosis factor alpha by monocytes from patients with pulmonary tuberculosis. AB - We studied the production of tumor necrosis factor alpha (TNF-alpha) by peripheral blood monocytes taken from patients with pulmonary tuberculosis and from healthy controls. It was found that the monocytes from patients with newly diagnosed tuberculosis released significantly greater amounts of TNF-alpha in vitro in response to lipopolysaccharide than did those from healthy controls (P less than 0.05). However, the monocytes from patients with chronic refractory tuberculosis released significantly lower amounts of TNF-alpha than did those from patients with newly diagnosed tuberculosis (P less than 0.005). Even when the cells were primed for 24 h with 500 U of recombinant interferon gamma per ml, the same pattern of results was observed. The depressed TNF-alpha production by the monocytes from patients with chronic refractory tuberculosis was also shown in response to Mycobacterium bovis BCG. This depressed TNF-alpha production did not recover, even when cultured for 1 to 7 days in the sera of healthy individuals. The sera from patients with chronic refractory tuberculosis did not have any suppressive effect on the lipopolysaccharide-induced TNF-alpha production. Thus, it was demonstrated that the levels of TNF-alpha produced by monocytes were related to the disease states of pulmonary tuberculosis and that the depressed TNF-alpha production by monocytes in patients with chronic refractory tuberculosis might not be acquired. PMID- 2205577 TI - Cloning and nucleotide sequence of a heat-stable enterotoxin gene from Vibrio cholerae non-O1 isolated from a patient with traveler's diarrhea. AB - We determined the nucleotide sequence of the heat-stable enterotoxin (STa) gene of the Vibrio cholerae non-O1 strain NRT36 isolated from a patient with traveler's diarrhea. The gene is chromosomally encoded and the presumed product is 78 amino acids in length, with a molecular weight of 8,814, though the genes of Escherichia coli STa(s) (STh and STp) are encoded in plasmid DNA and both products are 72 amino acids in length. The first 18 amino acids at the NH2 terminus were hydrophobic, suggesting that this region of the polypeptide acts as a signal sequence for the toxin. The last 17 amino acids at the COOH terminus were identical to those deduced from the toxin (NAG-ST) produced by V. cholerae non-O1 strain A-5 isolated from a frozen shrimp. The deduced amino acid sequence of the NAG-ST precursor had 50 and 46% homology to those of E. coli STh and STp, respectively. The hydropathy plot analysis of each predicted protein revealed similar profiles between them, suggesting that the NAG-ST precursor has structural similarity to those of E. coli STa(s). PMID- 2205578 TI - Diarrhea induced by Treponema hyodysenteriae: a young chick cecal model for swine dysentery. AB - The experimental infection of 25 young chicks with Treponema hyodysenteriae was carried out. Treponemes were isolated from 21 of 25 chicks on day 21 after inoculation. The ceca of chicks infected with treponemes were atrophied. The lumen was filled with a white watery fluid instead of digested feed. In some infected chicks, a cecal core was observed with the fluid in the cecum. The cecal core was grayish, hard, and rod shaped. It consisted of eroded cells and debris of treponemes and resembled the pseudomembrane. Bloody mucus was also observed in one chick. The thickness of the mucosae in 17 of 25 chicks were markedly increased. The histological changes were classified into two types. In the case of regressive changes of epithelial cells which mean severe erosion, the laminae propriae were exposed. Hemorrhage, edema, and heterophil infiltration in the laminae propriae were also confirmed. Numerous treponemes were observed within the edematous area under the remaining epithelia and also invaded the epithelial cells and laminae propriae. In the other case, progressive changes, that is, hyperplasia of mucosal epithelial cells and elongation of the crypt, were observed. The epithelia consisted mainly of cuboidal basophilic cells, mitotic cells, and goblet cells. The mitotic cells increased in number and were also observed near the superficial luminal surface of the ceca. Mucous goblet cells were also considerably increased in number. The erosion of superficial luminal epithelial cells was not so severe, but edema in laminae propriae was frequently observed. Electron-microscopic observation demonstrated that the basophilic epithelial cells were polyribosome rich, mitochondria poor, and lipid droplet poor. Furthermore, tonofibril-like structures under the terminal web in cytoplasms were lost, and numerous membrane-bound vesicles at the terminal web with free ribosomes were observed. In places, a number of vesicles were observed between microvilli, and some vesicles were released from the apical cytoplasm of epithelial cells. Microvilli also became scarce and irregular. The junctional complexes between cuboidal cells became unclear, the interdigitations between cuboidal cells became loose, and the intercellular spaces were widened. In conclusion, the appearance of numerous membrane-bound vesicles at the terminal web and the dilated intercellular space indicates increased secretion of water and electrolytes, and the abnormal proliferation of such immature epithelial cells indicates impaired absorption. On the basis of our findings, we can say that diarrhea induced by T. hyodysenteriae can be developed by synergism between impaired absorption and increased secretion by intestinal mucosae with hyperplastic immature epithelial cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2205579 TI - Vibrio cholerae HlyA hemolysin is processed by proteolysis. AB - The leukocidal activity of the Vibrio cholerae hemolysin (HlyA) was utilized to detect, enrich, and clone hybridoma cells expressing neutralizing monoclonal antibody in a new survivor selection protocol. A bank of 550 hybridoma clones was obtained from a mouse immunized with hemolysin by using standard techniques. The hybridoma bank was treated with a dose of HlyA hemolysin lethal to nonimmune clones. Five surviving hybridoma clones (X1 through X5) which possessed anti-HlyA activity were obtained. Western immunoblot analysis of V. cholerae culture supernatants with monoclonal antibody from clone X1 identified proteins with Mrs of 83,200, 71,600, and 60,300. Amino-terminal sequence analysis of the 71,600-Mr and 60,300-Mr forms showed homology with the published predicted sequence of HlyA. Our data indicate that proteolytic cleavage occurs between residues 120 and 121 (Glu-Leu) of the 83,200-Mr form, producing the 71,600-Mr form with the terminus NH2-L-L-F-T-P-F-D-Q-A-E-E-. Cleavage between residues 150 and 151 (Gly Phe) releases the 60,300-Mr form with the terminus NH2-F-A-S-P-A-P-A-N-S-E-. Calculations based on the DNA sequence and the N termini indicated that the actual molecular masses of the 83,200-, 71,600-, and 60,300-Mr forms were, respectively, 79.4 kilodaltons (kDa), 68.6 kDa, and 65.3 kDa. Survivor selection and amino-terminal microsequencing offer powerful tools for the analysis of leukotoxic agents. PMID- 2205581 TI - Biochemical and histologic findings in experimental pyelonephritis due to Ureaplasma urealyticum. AB - Ureaplasma urealyticum has previously been shown to be capable of persisting in the rat kidney for up to 6 months following a single reflux challenge. We examined kidney tissue from infected animals for evidence of renal damage by using standard cytochemical and immunoenzyme methods. We also monitored changes in renal function during a 6-month study period with standard biochemical assays of plasma and urine. Histologic examination showed tubular atrophy, interstitial fibrosis, and a mononuclear infiltrate in proportion to ureaplasma counts from renal tissue. The most severe damage was accompanied by hyaline cast formation within tubules which gave rise to the typical thyroidlike appearance of chronic pyelonephritis involving conventional urinary pathogens. Macroscopic renal scarring occurred in some animals. Although damage to the renal medulla was moderate to severe, only minor changes were seen in the cortex, and glomeruli were invariably spared. Biochemical tests of renal function showed similar changes in infected and uninfected animals during the study period. Interstitial inflammation was characterized by a mononuclear cell infiltrate in which polymorphonuclear leukocytes were not conspicuous. It is evident that U. urealyticum is capable of producing chronic pyelonephritis in the rat after a single reflux challenge. The results of this study have obvious implications for the pathogenicity of these bacteria in human pyelonephritis. PMID- 2205580 TI - Legionella pneumophila htpAB heat shock operon: nucleotide sequence and expression of the 60-kilodalton antigen in L. pneumophila-infected HeLa cells. AB - A 60-kilodalton (kDa) immunodominant antigen of Legionella pneumophila is a heat shock protein (HSP) of the GroEL class of HSPs. The gene (htpB) coding the 60-kDa protein was localized to a 3.2-kilobase DNA fragment of L. pneumophila cloned into pUC19 (pSH16) (P. S. Hoffman, C. A. Butler, and F. D. Quinn, Infect. Immun. 57:1731-1739, 1989). The nucleotide sequence of the DNA fragment cloned into M13 confirmed two open reading frames, htpA and htpB, that code for proteins of 96 and 548 amino acids, respectively. A consensus heat shock promoter sequence upstream of the start of htpA was identified, and no obvious promoter sequences were detected upstream of htpB. Amino acid sequence comparison studies revealed that the L. pneumophila HtpB protein exhibited 76% homology with the 65-kDa protein of Mycobacterium tuberculosis and 85% homology with both GroEL of Escherichia coli and HtpB of Coxiella burnetii. A comparison of the amino acid sequences among these proteins revealed several regions of nearly absolute sequence conservation, with the variable regions occurring in common areas. The purified L. pneumophila 60-kDa protein was antigenic for human T lymphocytes. Indirect fluorescent antibody studies indicated that the 60-kDa protein may be located in the periplasm or expressed on the surface by intracellular bacteria, suggesting that a stress-related mechanism may be involved in the expression of this immunodominant antigen. PMID- 2205582 TI - Development of an in vitro model for study of non-O1 Vibrio cholerae virulence using Caco-2 cells. AB - Non-O1 Vibrio cholerae strains have been reported as a causative agent of diarrhea throughout the world. We recently reported that non-O1 V. cholerae strains cause diarrhea in human volunteers. In this study we evaluated the virulence of three strains of non-O1 V. cholerae in a Caco-2 cell adherence assay by light and electron microscopy. A-5 is an environmental isolate which failed to colonized volunteers and did not cause diarrhea. It exhibited low numbers of organisms adherent to Caco-2 cells, leaving the microvilli intact. Strain 2076 79, isolated from a patient with diarrhea, colonized human volunteers without producing disease. It adhered to Caco-2 cells in moderate numbers without producing any damage to the microvilli. Strain NRT36S, a clinical isolate, colonized human volunteers and produced significant diarrhea disease. This strain adhered in very large numbers to Caco-2 cells and caused damage to the brush borders. Membrane-bound bacteria were also seen within the cytoplasm of these cells. Scanning electron microscopy confirmed the generalized adherence of NRT36S to the microvilli of Caco-2 cells. The three strains did not appear to compete with each other for binding sites on Caco-2 cells and were not adherent when assays were conducted at 4 degrees C. Our results with strains A-5, 2076-79, and NRT36S correlate well with observations in human volunteer studies, suggesting that Caco-2 cells provide an appropriate in vitro system for further investigation of the pathogenesis of non-O1 V. cholerae gastroenteritis. PMID- 2205584 TI - Principles of in vivo magnetic resonance spectroscopy in whole-body magnetic resonance systems. PMID- 2205583 TI - Association of rns homologs with colonization factor antigens in clinical Escherichia coli isolates. AB - rns is a trans-acting positive regulatory factor required for expression of the colonization factor antigen II (CFA/II) antigens CS1 and CS2 (J. Caron, L. M. Coffield, and J. R. Scott, Proc. Natl. Acad. Sci. USA 86:963-967, 1989). All 35 CFA/II-positive strains hybridized with a rns gene probe, as did all 10 CFA/I strains and all 4 CS4 strains. Hybridization with rns was detected in 25% of non enterotoxigenic Escherichia coli strains and was not detected in enteric pathogens with low G + C content. PMID- 2205585 TI - New approaches to body composition research: a reexamination of two-compartment model assumptions. AB - The field of human body composition research by necessity is based upon assumptions related to tissue chemical content. The 2-compartment model, which requires only 1 measurement in addition to body weight, is the cornerstone of current research in this field. Yet the assumptions upon which 2-compartment models are based were developed on a limited scale and their validity under specified conditions is questionable. Recent developments now allow quantification of previously unmeasured somatic constituents. The capacity to extend our models to 4 or more components is now at hand. Not only will this allow us to vastly expand our validation of two 2-compartment approaches, but our ability to explore new and important physiological questions is within reach. PMID- 2205586 TI - MR tomography and multinuclear MR spectroscopy in a whole-body MR system- applications in cancer research. PMID- 2205587 TI - Ultrasonic tissue characterization: its potential for the estimation of body masses. PMID- 2205588 TI - The ultrasonic measurement of upper arm muscle and fat area. PMID- 2205589 TI - Some aspects of body composition in cancer. AB - Changes in body composition, in cancer as in benign disease, simple starvation or overfeeding, show the integrated effect of a period of metabolic imbalance. Therefore, accurate measurements of body composition can help to elucidate the mechanisms that bring about the imbalance. Techniques of measurement that depend for their accuracy on the constancy of some property of the entire fat-free tissues are unlikely to give accurate results in obese or wasted patients. It is more informative, and more accurate, to measure fat, water, protein and mineral separately, and at present this is best done by dilution of labelled water and multi-element in vivo neutron activation analysis. Changes should be determined by sequential measurement wherever possible; otherwise results must be compared with 'normal' values found by measuring healthy subjects, correcting if necessary for differences in age and stature between patients and healthy subjects. PMID- 2205590 TI - A case for oral insulin therapy in the prevention of diabetic micro- and macroangiopathy. PMID- 2205591 TI - The invention of the artificial heart. PMID- 2205592 TI - Prevention of chronic glomerular uremia in steroid resistant glomerulonephritis. A clinical trial with a new antithrombotic agent. AB - To investigate the possibility of slowing down disease progression 27 patients with primary glomerular diseases unresponsive to steroids and cytotoxic drugs were treated with Defibrotide. This drug is a single stranded DNA fraction which has profibrinolytic and deaggregating properties and can promote the generation and release of prostacyclin from vascular tissue. Before treatment all patients showed proteinuria in excess of 1 g/day and 16 had a nephrotic syndrome (59%); 10 patients had serum creatinine above 1.6 mg/dl (37%) and 6 were hypertensive. After therapy a significant decrease in daily proteinuria was observed, although the reduction exceeded 50% of pre-treatment values in only 16 patients (59%). A progressive decrease in serum creatinine occurred in patients with abnormal renal function; serial measurement of renal plasma flow showed a progressive improvement with an average increase of 6 and 12%, after 1 and 3 months of treatment, respectively. These observations confirm the view that drugs improving endothelial function and renal hemodynamics can be of value in the treatment of chronic glomerular diseases and can contribute to the maintenance of renal function. PMID- 2205593 TI - Extracorporeal CO2 removal in a lung lavage induced respiratory distress syndrome. AB - Ten pigs with experimental respiratory distress syndrome were treated by extracorporeal CO2 removal (ECCO2-R) combined with low frequency positive pressure ventilation (LPPV). After lung damage had been induced by repeated lung lavages a PEEP trial was conducted in order to find the appropriate PEEP for the damaged lungs. This PEEP was then applied during the ECCO2-R/LPPV period. Blood gas values improved significantly on extracorporeal bypass within a short time (pre-bypass paO2: 54.2 +/- 3.7 vs 168.5 +/- 31.6 mmHg after 15 min on bypass, p less than 0.001) and were kept constant during the next 4 hours. Minute ventilation (MV) was reduced from 4.01 +/- 0.31 to 0.74 +/- 0.07 l/min (p less than 0.0001), FiO2 of the ventilator from 1.0 to 0.46 +/- 0.08 (p less than 0.0001) whereas FiO2 of the membrane lung (ML) was not changed significantly (FIO2ML 0.59 +/- 0.07 vs 0.53 +/- 0.06). During controlled mechanical ventilation (CMV), comparable adequate gas exchange was only achieved at a significantly higher mean airway pressure (Paw 14.1 +/- 0.08 vs 21.2 +/- 0.47 cmH20, p less than 0.0001). Hemodynamic variables did not change significantly during bypass time. ECCO2-R/LPPV driven by a simple renal perfusion system allows adequate gas exchange in experimental respiratory failure. PMID- 2205594 TI - Conjugated human hemoglobin as a physiological oxygen carrier--pyridoxalated hemoglobin polyoxyethylene conjugate (PHP). AB - Problems associated with specific physiological properties of Hb-based blood substitutes, such as low P50, short plasma half-life and nephrotoxicity are still major issues to be addressed. Extensive investigations aimed at overcoming these problems have resulted in the preparation of pyridoxalated-hemoglobin polyoxyethylene conjugate (PHP). PHP was developed from human hemoglobin by two major chemical modifications; pyridoxylation for the purpose of lowering the oxygen affinity (P50 of 19.5 +/- 1.2 mmHg), and coupling with polyoxyethylene (POE) to increase its molecular weight (to approximately 90 kdaltons). The circulating half-life of PHP is about 40 hours in dogs. Toxicological and physiological studies including renal function assessments have demonstrated that PHP does not have untoward effects on major organ functions. Its efficacy in transporting oxygen has been shown in ET and intracoronary perfusion, and in in vitro studies with sickle cells. Studies to date suggest that PHP is a promising candidate as a physiological oxygen carrier. In this paper the properties of PHP, its safety and efficacy aspects, and its potential as a clinical oxygen carrier are reviewed based on studies conducted in the Author's laboratory. PMID- 2205596 TI - Campylobacter pylori in Israel: prospective study of prevalence and epidemiology. AB - Antral biopsy samples were taken from 147 patients undergoing gastroscopy. Campylobacter pylori was cultivated from 100 of these patients. C. pylori was isolated from 76% of the specimens showing any degree of histologic gastritis, but from only 11% of specimens with completely normal histology. A questionnaire was completed on all patients and included demographic, epidemiologic and clinical information. Sephardic origin, smoking, and a bad taste in the mouth were more prevalent in the campylobacter-positive group. Previous use of antibiotics was negatively associated with the presence of C. pylori. Histologically confirmed gastritis was highly associated with the presence of C. pylori, especially in the moderate or severe grades in which 84% of biopsy specimens were positive. C. pylori was also cultivated from 50% of patients with mild gastritis, in 88% of patients with duodenal ulcer and in 71% of patients with gastric ulcer. The presence of C. pylori in 11% of normal specimens and the absence of C. pylori in 24% of specimens with gastritis further raises the question of the exact role played by C. pylori in the etiology of gastritis. PMID- 2205595 TI - Comparisons between the three-dimensional structures of the chemotactic protein CheY and the normal Gly 12-p21 protein. AB - The three-dimensional structure of a chemotactic protein CheY from Salmonella typhimurium has recently been determined by X-ray crystallography. The structure of this small protein, containing 129 amino acid residues, shows a domain consisting of a central beta-pleated sheet surrounded on both sides by alpha helices. We have examined the sequence and the arrangement of the structural domains of the CheY protein and have compared them with other nucleotide binding protein sequences and structures. We find that the CheY protein has significant sequence homology to the ras-gene encoded p21 protein. In addition, the structural domains of the two proteins are arranged in a fundamentally similar manner, including the phosphate-binding site (both proteins bind phosphate containing ligands). The striking similarity in the arrangement of the structural domains of the two proteins suggests that both may serve similar functions as signal transducers. PMID- 2205597 TI - The myelodysplastic syndromes--1990. PMID- 2205599 TI - [Formalin-resistant leukocyte differentiation antigens in dermatohistopathology]. AB - The diagnosis of cutaneous leucocytic and particularly lymphocytic infiltrates with a considerable degree of reliability, has become possible owing to the use of monoclonal antibodies against leucocyte differentiation antigens. This method of diagnosis depends heavily on the availability of frozen biopsies, however, since most antigens are destroyed by the routine tissue processing, including formol fixation, paraffin embedding and alcohol dehydration. In recent years an increasing number of antibodies has become available that allow the detection of formalin-resistant leucocyte differentiation antigens and thus can be used on conventional paraffin sections. When using such antibodies, which will be invaluable in routine diagnosis and, furthermore, will allow the investigation of old biopsies, the dermatopathologist must be familiar with the exact distribution of the detected antigen and should be aware of crossreactivities with other structures. This review presents the most important antibodies and gives hints on their rational and economical use. PMID- 2205598 TI - Double blind comparison of lithium and verapamil in cluster headache prophylaxis. AB - Chronic Cluster Headache (CCH) treatment is troublesome; since there are no pain free periods, it must be continuous. The most effective CCH prophylactic drug today is lithium carbonate but long-term use of this drug is limited by the possibility of side effects. Recently, calcium antagonists have been successfully employed to prevent migraine, and preliminary studies also indicate that verapamil in particular is an efficacious treatment for CCH. We have conducted a multicenter trial employing a double-dummy, double blind, cross-over protocol, comparing verapamil with the established efficacy of lithium carbonate, in preventing CCH attacks. Both lithium carbonate and verapamil were effective in preventing CCH but verapamil caused fewer side effects and had a shorter latency period. We did not observe any correlation between plasma levels of the two drugs and their clinical efficacy. Both the drugs tested here may exert their effect by restoring a normal inhibitory tone to the pain modulating pathways from the trigemino-vascular system, a circuit putatively implicated in CCH. PMID- 2205600 TI - [Value of high resolution ultrasound in determination of vertical tumor thickness in malignant melanoma of the skin]. AB - The maximal thickness of a primary malignant melanoma of the skin can be determined preoperatively by means of modern high-frequency ultrasound scanners (20 MHz). In this way operative therapy can be planned and the minimal excision margins can be determined before surgery. The present study demonstrates a strong correlation (r = 0.97) between preoperative ultrasound and postoperative histometric determination of tumour thickness in 72 primary malignant melanomas. The study showed, however, that ultrasound scanners cannot distinguish unequivocally between histologically confirmed tumour cell aggregates and subtumoral remnants of a benign melanocytic naevus or subtumoral lymphocytic infiltrates. In these cases, determination of tumour thickness by ultrasound yields higher values for thickness than do histological examinations. In addition, tumour cell aggregates that are smaller than the lower limit of scanner resolution, are very close to the main tumour mass, or have infiltrated the deeper dermis cannot be measured accurately. In these cases, ultrasound examination underestimates the tumour thickness. PMID- 2205601 TI - [Topical therapy in pregnancy]. AB - Any instance of drug administration during pregnancy can pose problems and will always take place after careful consideration and specific benefit risk evaluation. Even in the case of local therapy, which is rightly considered particularly safe, several active substances are applied whose embryotoxic potential is either relevant when given systemically in animals or humans, or unknown. With this in mind, several active substances designed for topical application are discussed that should not be applied at all during pregnancy or only within defined periods, even under various conditions of local therapy. The borderlines are unclear, and are indicated with particular reference to areas for which no reliable data are available. PMID- 2205602 TI - [Encapsulated neuroma of the skin. A clinical, histologic and immunohistologic study]. AB - Encapsulated neuroma of the skin is a little known, though not especially rare, benign tumour of the peripheral nerve system. It is often wrongly diagnosed on the basis of both clinical and histological investigation. We have subjected 24 encapsulated neuromas to clinical, histological, and immunohistological study. Clinically, they presented as solitary, skin-coloured small nodules, usually located on the face in middle-aged adults. Histologically, encapsulated neuromas are well-circumscribed dermal tumours. They are composed of interlacing fascicles of Schwann cells (S-100 protein +) and numerous tiny axons (S-100 protein +, neurofilament +). Most reveal at least partial encapsulation with perineurial differentiation (EMA +, vimentin +). Encapsulated neuromas can be differentiated from other tumours of the peripheral nerve system and from leiomyoma by their distinctive histological and immunohistological features. PMID- 2205603 TI - [The fractals theory and its significance for dermatology]. AB - Classic mathematical methods are frequently not suitable for the investigation of complex "natural" shapes, that cannot be approximated by geometric structures. A theory developed by Mandelbrot has made it possible to analyse such "fractals". Many biological and medical shapes could be identified as fractal. These results suggest fractal structures for some dermatological lesions. This is particularly true for skin lesions related to the vascular system (e.g., livedo racemosa, spider naevus). Furthermore, computer simulation of pathogenetic mechanisms can demonstrate that the lesions of a skin disease are fractal in nature. This method can be applied to skin tumours with horizontal cell growth (e.g., carcinoma and melanoma in situ) and to the architecture of spider naevus. PMID- 2205604 TI - [Cutaneous manifestation of fungal infection]. AB - A 50-year-old patient with an aplastic syndrome developed disseminated purpuric, necrotic lesions on his skin. Histological examination revealed fungal sepsis. The clinical appearance, the course of the disease are described and the importance of histological examination is pointed out. PMID- 2205606 TI - [Nasal nodular fibrosis, Sutton nevus and dermatofibroma in oil paintings by famous artists]. PMID- 2205605 TI - [Unusual primary cutaneous localized amyloidosis]. AB - The case of a 41-year-old female patient with an unusual type of primary localized cutaneous amyloidosis is reported. Clinical examination revealed lesions typical for macular cutaneous amyloidosis, while histology and histochemistry, in contrast, revealed the presence of nodular amyloidosis of the skin with deposition of lambda light chain amyloid. PMID- 2205607 TI - Suppressive action of gonadotropin-releasing hormone and luteinizing hormone on function of the developing ovine corpus luteum. AB - Experiments were conducted to examine the effects of exogenous GnRH and LH on serum concentrations of progesterone (P4) in the ewe. Ewes in Exp. 1 and 2 were laparotomized on d 2 of an estrous cycle and ewes with corpora lutea (CL) in both ovaries were unilaterally ovariectomized. Ewes with CL in one ovary only were not ovariectomized. While they were anesthetized, ewes (n = 5) were injected with 25 micrograms GnRH (Exp. 1) or 50 ng GnRH (Exp. 2) into the artery supplying the ovary bearing the CL. Control ewes (n = 5 in each experiment) were injected similarly with saline. In Exp. 3, six ewes were injected i.v. (jugular) on d 2 with 100 micrograms oLH (t = 0) and 50 micrograms oLH at 15, 30 and 45 min; six control ewes were injected similarly with saline. Jugular blood was collected from all ewes at frequent intervals after treatment for LH analysis and on alternate days of the cycle through d 10 or 11 for P4 analysis. Treatment with 25 micrograms GnRH increased serum concentrations of LH at 15, 30, 45 and 60 min postinjection (P less than .001) and reduced serum concentrations of P4 on d 7 through 11 (treatment x day interaction; P less than .05). Injection with 50 ng GnRH caused a slight increase in serum concentrations of LH at 15 min but had no effect on serum concentrations of P4.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2205608 TI - Effects of isoenergetic infusions of propionate and glucose on portal-drained visceral nutrient flux and concentrations of hormones in lambs maintained by total intragastric infusion. AB - Three lambs were used in a repeated Latin square design to determine the influence of isoenergetic infusions of propionate or glucose on portal-drained visceral flux (PDV) of nutrients and concentrations of insulin, glucagon, growth hormone and prolactin. Lambs were fitted with appropriate catheters for blood sampling and maintained on total intragastric infusion of nutrients. Basal VFA, casein, mineral and vitamin infusions (isocaloric and isonitrogenous) were supplemented with an additional 22 +/- .5 kcal/h from propionate, glucose or a combination of propionate plus glucose. Ruminal fluid proportion and arterial blood concentration and PDV flux of propionate increased (P less than .10) by 17 mol/100 mol, .02 mM and 40 mmol/h, respectively, with infusion of an additional 61 mmol/h of propionate. Regression equations predicted that, on a net basis, 67% of ruminally infused propionate and 43% of abomasally infused glucose appeared in portal blood. Arterial L-lactate, beta-hydroxybutyrate and acetate concentrations, and beta-hydroxybutyrate flux were increased (P less than .10) by .34 mM, .20 mM, .50 mM and 4.2 mmol/h, respectively, with infusion of 33 mmol/h of added glucose. Net utilization of glucose by the PDV was approximately 4.4 mmol/h when no glucose was infused. Increased infusion of propionate resulted in a 22.2-micrograms/h increase in PDV flux of insulin (P less than .08) but had no effect on arterial insulin, glucagon and prolactin concentrations (P greater than .10). Arterial growth hormone increased by 3.8 ng/ml with increasing glucose infusion (P less than .08).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2205609 TI - Effects of auricular acupuncture-like transcutaneous electric nerve stimulation on pain levels following wound care in patients with burns: a pilot study. AB - This study was designed to test the hypothesis that auricular acupuncture-like transcutaneous electrical nerve stimulation would significantly reduce the pain experienced by patients with burns immediately after wound debridement, other wound care, and dressing changes. Subjects were 11 inpatients at the University of Alabama Hospital Burn Unit. A two-period crossover design was used, and each patient received one experimental treatment consisting of bilateral acupuncture like transcutaneous electrical nerve stimulation to six ear points and one control treatment consisting of a placebo pill. The Visual Analogue Scale was used as a measure of pain and was completed immediately before and after treatments and at 15, 30, and 60 minutes after treatment. A two-factor repeated measures ANOVA indicated significant effects of measurement time (p less than 0.001) and treatment by time (p = 0.002). Post hoc analysis revealed significant differences (p less than 0.05) between experimental and control conditions at all times after treatment but not at pretreatment baseline. These results indicate that auricular acupuncture-like transcutaneous electrical nerve stimulation may be an effective pain management technique in patients with burns. PMID- 2205610 TI - Prospective randomized comparison of two types of pressure therapy garments. AB - A prospective randomized study was undertaken to compare compliance efficacy and cost of the elastic nylon pressure garment (Jobst Institute, Inc., Toledo, Ohio) with the cotton elastic pressure garment (Tubigrip, SePro Healthcare Inc., Montgomeryville, Penn.). Of 110 patients enrolled, 54 received Jobst pressure garments and 56 received Tubigrip pressure garments. Time spent in pressure therapy garments was the same for both groups. Comparable clinical results were achieved with either Tubigrip or Jobst garments. A significantly greater percentage of patients were compliant with Tubigrip pressure-garment therapy than with Jobst pressure-garment therapy. The cost of the Tubigrip garments was significantly lower than that of Jobst garments. These data suggest that the use of elasticized cotton pressure garments results in significantly better patient compliance, a lower cost, and equal therapeutic efficacy when compared with the elasticized nylon pressure garments. PMID- 2205611 TI - Treatment of postextubation stridor in a pediatric patient with burns: the role of heliox. AB - Stridor is a common problem in patients with burns after extubation, especially in children and in those with facial burns or airway injuries. The usual treatments for severe respiratory distress, such as reintubation and tracheotomy, carry substantial risks for patients. We report our successful treatment of severe postextubation stridor in a 7-year-old patient with burns with the administration of heliox in addition to more traditional therapies, review the literature about the use of heliox in postextubation stridor, and suggest cases in which its use may prevent the need for more hazardous interventions. PMID- 2205612 TI - The development of a discharge planning index for use in a pediatric acute burn unit. AB - The purpose of this study was to develop a discharge planning index for use in a pediatric acute burn unit. The study sample consisted of 59 health professionals from a pediatric burn hospital who had worked at least one year with children with acute burns and their families in discharge planning. With the use of the Delphi technique, a three-round survey was conducted. A Pediatric Acute Burn Discharge Planning Index that consists of 75 items was developed on the basis of the items that received a mean score of 5.0 or greater in the third survey. The data were further analyzed with Spearman's rank correlation coefficient to compare the top 23 rank-ordered items rated by the nursing department with those rated by the other departments surveyed. The rank-order correlation showed a positive correlation between the nursing department's and other departments' responses. These results indicate that all health team members agree on the importance of assessing the items listed on the derived index before discharging a pediatric patient with acute burns. PMID- 2205613 TI - Rapid protein purification using phenylbutylamine-Eupergit: a novel method for large-scale procedures. AB - Electrophoretic desorption was used to compare the protein binding capacities of some hydrophobic adsorbents [the phenylbutylamine (PBA) derivatives of Eupergit C and agarose and Phenyl-Sepharose] for low-pressure chromatography. The highest capacity was observed for the bifunctional adsorbent PBA-Eupergit. The hydrophobically adsorbed proteins can be selectively desorbed by decreasing the pH of the eluent due to electrostatic repulsion between positive charges on the adsorbed proteins and positively charged secondary amines on the adsorbent. This was used to purify 1500 U penicillin amidase from E. coli homogenates per gram wet weight of PBA-Eupergit in 50 adsorption-desorption cycles without organic solvents (greater than 90% yield, purification factor = 5.3). PMID- 2205614 TI - Screening method for large numbers of dye-adsorbents for enzyme purification. AB - A method is described by means of which 96 different dye-adsorbents can be tested simultaneously for their ability to bind enzymes and to test their biospecific elution. Small amounts of cell-free extract are applied to dye-adsorbents which are packed in a 96-well transplate cartridge. After biospecific elution, the amount of the eluted enzyme is tested in a microtitre plate assay. The method is illustrated by the purification of glycerol dehydrogenase (E.C. 1.1.1.72), 6 phosphogluconate dehydrogenase (E.C. 1.1.1.44) and glucose-6-phosphate dehydrogenase (E.C. 1.1.1.49) from the hyphal fungus Aspergillus nidulans. PMID- 2205615 TI - Sensitive blotting assay for the detection of glycopeptides in peptide maps. AB - A dot blotting assay using digoxigenin hydrazide (Glycan detection kit, Boehringer Mannheim Biochemicals) was used to screen an endoproteinase Lys-C peptide map of ribonuclease B for the presence of glycopeptides. The carbohydrate content of the identified glycopeptide fraction was then further characterized by monosaccharide analysis using high-pH anion-exchange chromatography with pulsed amperometric detection (HPAE-PAD). The tandem use of a hydrazide dot blotting technique to screen peptide maps for glycopeptides and subsequent use of HPAE-PAD to identify the monosaccharide composition of glycopeptide hydrolyzates proved to be a quick, sensitive and reliable method for identifying glycopeptides and analyzing their glycan composition without derivatization of the carbohydrate. PMID- 2205616 TI - Purification of the upstream element factor of the adenovirus-2 major late promoter from HeLa and yeast by sequence-specific DNA affinity chromatography. AB - The purification to homogeneity of the Adenovirus-2 major late promoter (MLP) upstream element factor (UEF), a sequence specific transcription factor, which binds to upstream elements of various class B (II) genes, is reported. The protein was purified from HeLa cells and also from the yeast Saccharomyces cerevisiae, by using sequence-specific DNA affinity chromatography. The human (UEFh, 45,000 dalton) and the yeast (UEFy, 60,000 dalton) proteins protect the same sequences over the MLP-IVa2 intergenic region: the MLP-UE (from nucleotide 49 to -67) and the IVa2-UE (from nucleotide -98 to -122 relative to the MLP initiation site). Both proteins have a higher affinity for the MLP-UE than for the IVa2-UE. PMID- 2205617 TI - Progress in affinophoresis. AB - The use of polyionic polymers as mobile affinity matrices in electrophoresis has led to the development of a specific separation method for biological substances, affinophoresis. The conjugate of a polyionic polymer and an affinity ligand is called an affinophore. Electrophoresis of proteins in the presence of an affinophore results in a change in the mobility of a specific protein due to the difference between the mobility of the protein and that of the protein affinophore complex. Polylysine is useful as a base polymer of affinophores and has been used successfully as an anionic matrix after succinylation. Affinophoresis of proteases, lectins and antibodies has been carried out in agarose gel and the mobility of the protein having affinity to each ligand was specifically changed. Two-dimensional affinophoresis, in which an affinophore was included only in the second-dimensional electrophoresis, was effective for the separation of the components of a complex mixture of proteins even if the change of mobility was not large. Red blood cells were successively treated with homologous antiserum, biotinylated second antibody, avidin and biotinylated succinylpolylysine as an affinophore. Specific acceleration of the homologous cells to the antiserum was observed even when the affinophoresis was applied to mixed red blood cells from different species. PMID- 2205618 TI - Application of avidin-biotin technology to affinity-based separations. AB - During the last decade, avidin-biotin technology has become a commercially viable tool for research, medical and industrial applications. From the beginning, mediation via the avidin-biotin complex was proposed for affinity-based separations. This particular application, however, has been slow in gaining acceptance. One of the reasons is that the strength of binding between avidin and biotin is sometimes inappropriate for the desired affinity system. Another problem involves certain "undesirable" structural properties in the avidin molecule which may lead to high levels of "non-specific" binding. Recent progress in understanding the molecular requirements for binding biotin may eventually lead to the design of avidin-like proteins which will exhibit preferred recognition properties according to the desired application. PMID- 2205619 TI - Biosensors. AB - This review introduces biosensors as analytical devices that respond selectively to analytes in appropriate samples and convert their concentrations into electrical signals via a combination of a biological recognition system and a suitable transducer. The last decade has seen dramatic advances in the design of sensor configurations, the marriage of biological systems with modern monolithic silicon and optical technologies, the development of effective electron-exchange systems and the introduction of direct immunosensors. PMID- 2205620 TI - Application of receptor-affinity chromatography to bioaffinity purification. AB - Receptor-affinity chromatography based upon the receptor-ligand interactions has been utilized for the purification of recombinant human interleukin-2 (rIL-2) from microbial and mammalian sources. The receptor-affinity purification process of rIL-2 is used as a model system to demonstrate the utility of this approach for the purification of recombinant proteins. The receptor-affinity purified biomolecule is shown to be biochemically and biologically more homogeneous than the immunoaffinity purified material. PMID- 2205621 TI - High plasma prorenin in diabetes mellitus and its correlation with some complications. AB - Plasma prorenin is abnormally high, whereas renin is normal or even low, in many patients with long-standing diabetes mellitus complicated by microvascular disease. Nephropathy or autonomic neuropathy has been put forward as a cause. We found that in 223 consecutive diabetics prorenin correlated positively with serum creatinine, the presence of macroalbuminuria (greater than 250 mg/L), and the presence of diabetic retinopathy, particularly the proliferative type. This correlation did not depend on the presence of neuropathy or whether the patient was receiving insulin. It was also independent of sex, age, duration of diabetes, blood pressure, and blood levels of glucose and hemoglobin-A1c. The association between elevated prorenin and retinopathy remained significant after adjustment for creatinine and the presence of macroalbuminuria. Of the whole group of diabetics 94 consecutive patients were assessed for the presence of microalbuminuria (30-300 mg/24 h). Independently of the presence of micro- or macroalbuminuria, the mean level of prorenin was not above normal in the patients without retinopathy and was 2-3 times normal in those with proliferative retinopathy. Thus, retinopathy appears to be a more important determinant of abnormally high prorenin than nephropathy. In addition, the renal vein to artery ratio of prorenin in 7 diabetics with both advanced nephropathy and proliferative retinopathy was not elevated, despite the high peripheral venous prorenin level and the impaired renal perfusion. Thus, the abnormally high prorenin level in these patients could not be explained by abnormal secretion by the kidneys. Finally, prorenin was not high in 16 nondiabetics with loss of sympathetic activity due to chronic autonomic neuropathy, which indicates that in the absence of diabetes, this type of autonomic failure is not sufficient to cause the high prorenin levels seen in diabetics. Our findings are evidence that abnormally high plasma prorenin levels in diabetics are not an immediate consequence of altered glucose metabolism. This abnormality is related to the development of microvascular disease in the eye and kidney and is at least in part due to decreased clearance of prorenin from the circulation, increased production from extrarenal sources, or both. PMID- 2205623 TI - Clinical review 14: Pathophysiology and treatment of sexual precocity. PMID- 2205622 TI - Cytochrome P450IIE1 is elevated in lymphocytes from poorly controlled insulin dependent diabetics. AB - Cytochrome P450IIE1, a member of the cytochrome P450 supergene family, was measured in peripheral lymphocytes of 14 patients with insulin-dependent diabetes mellitus who were in poor metabolic control, as evidenced by elevated hemoglobin A1 levels (mean, 11.9 +/- 2.8%; normal, less than 7.8). Only one major form (mol wt, 48,000 daltons) of cytochrome P450IIE1 was detected with a specific polyclonal antibody against P450IIE1. Levels of cytochrome P450IIE1 were very low to undetectable in human lymphocytes from seven normal subjects. However, levels of P450IIE1 were elevated in lymphocytes from patients with insulin-dependent diabetes mellitus. Elevated levels of cytochrome P450IIE1 determined by immunoblot analysis correlate positively with the levels of hemoglobin A1 (r = 0.8), a metabolic indicator in diabetic subjects. In one study subject in whom diabetic control was improved, the drop in hemoglobin A1C levels was accompanied by normalization of P450IIE1 levels. PMID- 2205624 TI - 17 Beta-estradiol and continuous norethisterone: a unique treatment for established osteoporosis in elderly women. AB - Forty women aged 64.7 +/- 5.1 yr with established postmenopausal osteoporosis were blindly allocated to 1 yr's treatment with either continuous combined estrogen/progestogen therapy (2 mg estradiol + 1 mg norethisterone acetate + 500 mg calcium daily) or placebo + 500 mg calcium daily. In the group treated with hormones bone mineral density in the spine (dual photon absorptiometry) and bone mineral content in the ultradistal forearm (single photon absorptiometry) increased highly significantly by 8-10% during the 1 yr of treatment. Bone mineral content in the mid-shaft of the forearm (single photon absorptiometry) and the total body bone mineral (dual photon absorptiometry) increased by 3-5% when compared to that in the placebo group, which showed virtually unchanged values at all measurement sites. Seven of the women treated with hormones were examined after a further year of treatment. BMC increased by another 3-6%, reaching a 12% increase in bone mineral density in the spine after 2 yr of treatment. Biochemical estimates of bone resorption (fasting urinary calcium and hydroxyproline) and bone formation (serum alkaline phosphatase and plasma osteocalcin), decreased significantly (P less than 0.001) in the group treated with hormones, but remained unchanged in the placebo group. The reduction in indices of bone resorption was more pronounced than that in bone formation after one year, indicating a positive bone balance. No further changes were seen in these bone turnover parameters during the second year of treatment. In the group treated with hormones, serum levels of triglycerides, total cholesterol, and low density lipoprotein cholesterol decreased by about 12% (P less than 0.05-P less than 0.01), whereas high density lipoprotein cholesterol decreased by about 8% (P less than 0.001). The high density lipoprotein cholesterol/low density lipoprotein cholesterol ratio was unchanged. The hormone treatment did not produce any major side effects, and only minor bleedings were experienced by a few women. The present study demonstrates that treatment with female sex hormones in this particular combination is a realistic approach to the treatment of women with established postmenopausal osteoporosis. PMID- 2205625 TI - Hormonal responses to a potent gonadotropin hormone-releasing hormone antagonist in normal elderly men. AB - GnRH analogs, both agonists and antagonists, have potential use in androgen dependent diseases of older men, such as prostatic cancer and benign prostatic hyperplasia. Previous experience with agonists of GnRH has suggested that GnRH analogs may be more effective in aged men than in young men, but little is known about GnRH antagonists in older men. Therefore, we evaluated the hormonal effects of a single dose and a short course of a GnRH antagonist (Nal-Glu) in normal elderly men. Six young men (25-34 yr old) and six older men (66-76 yr) each received single morning injections of Nal-Glu (25, 75, and 250 micrograms/kg), separated by 2 weeks. Serum levels of testosterone (T), immunoreactive LH (LH RIA) and FSH (FSH RIA), and bioactive LH (LH BIO) were evaluated periodically for 7 days after each injection. In addition, six elderly men received 25 and 75 micrograms/kg.day Nal-Glu for 10 consecutive mornings each, and serum levels of T, inhibin, LH RIA, LH BIO, FSH RIA, and bioactive FSH were evaluated. Nal-Glu in all three single doses caused a significant (P less than 0.01) decline in serum levels of T and gonadotropins that was similar in extent in the elderly and young men. For example, T declined to a level of 19% of baseline after the 250 micrograms/kg dose of Nal-Glu in both age groups. For both the young and elderly men, the major effect of increasing the Nal-Glu dose was a prolongation of the period of suppression. Multiple Nal-Glu injections in the elderly men also resulted in a rapid decline in T, inhibin, and bioactive and immunoreactive gonadotropins. For both LH and FSH, bioactivity decreased to a greater extent than immunoreactivity. Local side-effects of Nal-Glu tended to be fewer and of less intensity in the elderly men compared to those in the young men. These results demonstrate that the response to Nal-Glu in healthy elderly men is similar to that in younger men, and extended administration of Nal-Glu in elderly men effectively suppresses gonadal and pituitary function. These results suggest that the role of GnRH antagonists in the effective treatment of androgen dependent disease in the aging male needs to be explored further. PMID- 2205626 TI - The dual effect of epidermal growth factor upon human chorionic gonadotropin secretion by the first trimester placenta in vitro. AB - Epidermal growth factor (EGF) is believed to play an important role in the regulation of placental function. We have examined the effect of EGF upon first trimester (7-10 gestational weeks) placental hCG secretion and cellular differentiation using both static (explants and isolated cells) and kinetic (superfusion of explants) culture methods. In superfused explants, short (1-4 min) pulses of EGF increased both the rate and amplitude of spontaneous pulsatility of hCG. The frequency increased from 3/h to 5/h, and the amplitude increased compared to the control channels as calculated by the area under the curve. This effect was dose dependent and the concentration of 50 ng/ml, which was the lowest dose tested, was the most effective. In explants cultured for 24 h, EGF caused a 2-fold increase in hCG secretion, compared to control, P less than 0.05. In two different dispersed trophoblastic cell cultures, EGF added daily for the first week caused a 180% increase in hCG secretion, P less than 0.05. However, according to morphological criteria, i.e. light microscopy and vital staining, no significant effect upon the rate of differentiation to syncytiotrophoblast was observed in long-term cultures of one of these preparations. In conclusion, EGF plays a dual trophic role in stimulating hCG secretion in the first trimester. However, this effect is not dependent on cellular differentiation. PMID- 2205627 TI - Assessment of growth hormone secretion in normal stature children using 24-hour integrated concentration of GH and pharmacological stimulation. AB - The integrated concentration of serum GH (IC-GH) is used for the assessment of spontaneous GH secretion. In order to use the IC-GH as a diagnostic tool a normative reference range needs to be established. We determined the IC-GH by continuous blood withdrawal in 119 children of normal height, weight and growth rate. Although the mean IC-GH increased with pubertal status, 4.4 +/- 1.2 micrograms/L at Tanner I (n = 36), 5.5 +/- 2.1 micrograms/L at Tanner II-III (n = 43), and 5.8 +/- 1.6 at Tanner IV-V (n = 40) (P less than 0.03), there was a considerable overlap of individual IC-GH levels between the pubertal groups. Gender affected the mean IC-GH level slightly, but not the range. Although the mean IC-GH of girls tended to be higher than that of boys this difference was not statistically significant. Ninety five percent of the IC-GH values were above the 3.2 micrograms/L level. The response to pharmacological stimulation (clonidine, insulin, or arginine) was also evaluated in 68 of the subjects. The peak GH response to pharmacological stimulation (micrograms/L) with clonidine 21.0 +/- 10.7 (n = 66) was significantly higher than to either arginine 13.1 +/- 6.1 (n = 23) or insulin 14.2 +/- 6.3 (n = 19) (P less than 0.01). The peak response to clonidine increased significantly with pubertal status (P less than 0.001) and there was an interactive effect of gender and pubertal stage where the GH response of prepubertal boys exceeded that of prepubertal girls but the response of pubertal girls exceeded that of pubertal boys (P less than 0.02). The peak stimulated GH levels was correlated with IC-GH in this subgroup r = 0.52, P less than 0.0001). This study provides a large normative data base for IC-GH and the GH provocative tests in normally growing children of varying pubertal status. PMID- 2205628 TI - Hypocortisolemia in children undergoing evaluation for growth hormone deficiency. AB - The group of children who have clinical manifestations of GH deficiency may potentially contain a large number of patients with secretory defects of cortisol. We assessed physiological cortisol secretion by measuring the 24-h integrated concentration of cortisol (IC-F) in a series of 105 patients, aged 7 19 yr, undergoing endocrinological evaluation for growth impairment possibly due to GH deficiency. The reference value for IC-F, established from 30 normal stature, normal weight children (controls), aged 7-18 yr, was 157 +/- 41 nmol/L (mean +/- 1 SD). There was no effect of age, gender, or pubertal status on IC-F in controls. The IC-F of patients was 150 +/- 72 nmol/L. Twelve patients (11%) had IC-F values more than 2 SD below the mean (i.e. less than 75 nmol/L) of the controls (P less than 0.001). An IC-F below 75 nmol/L was associated with a blunted peak cortisol response to insulin-induced hypoglycemia (367 +/- 160 nmol/L compared to 464 +/- 155 nmol/L in the other patients; (P less than 0.05). None of the patients had obvious clinical symptoms of hypocortisolemia at the time of testing. In general, IC-F levels were not correlated with IC-GH. However, 10 patients who had subnormal IC-F values also had laboratory evidence of GH secretory defects; 7 had subnormal IC-GH levels but normal stimulated GH responses, and 3 had both subnormal responses to stimulation as well as subnormal IC-GH. The long term prognosis and management implications of hypocortisolemia diagnosed in this patient group require further evaluation. PMID- 2205629 TI - Secondary hypogonadism in older men: its relation to impotence. AB - The relation of the reproductive endocrine system to impotence in older men was examined by measuring the concentrations of testosterone (T), bioavailable testosterone (BT), LH, and PRL and body mass index (BMI) in 57 young controls (YC), 50 healthy potent older controls attending a health fair (HF), and 267 impotent patients (SD). The SD and HF had markedly reduced mean T and BT values compared to YC. When adjusted for age and BMI there was no difference in BT between potent and impotent older men. The percent BT was much higher in YC than in the older groups. While the percent BT rose significantly with increased T in YC, it was inversely related to T in the older subjects, suggesting that increased sex hormone-binding globulin binding was a primary event leading to a low BT. Forty-eight percent of HF and 39% of SD were hypogonadal, as defined by a mean BT of 2.5 SD or more below the mean of YC (less than or equal to 2.3 nmol/L). Ninety percent of these had LH values in the normal range, suggesting hypothalamic-pituitary dysfunction. Thirty-four SD and six each of YC and older control volunteers (OC) underwent GnRH testing. Older subjects showed impaired responsiveness to GnRH compared to YC. A low basal LH level correlated very highly with hyporesponsiveness to GnRH. Thus, secondary hypogonadism and impotence are two common, independently distributed conditions of older men. PMID- 2205631 TI - Muscle protein interaction; competition by peptide mimetics. PMID- 2205630 TI - Treatment with a somatostatin analog decreases pancreatic B-cell and whole body sensitivity to glucose. AB - To determine the specific alteration in B-cell function caused by a somatostatin analog in man and to determine the effect of the induced insulin deficiency on insulin action, we administered octreotide (SMS 201-995; 50 micrograms twice daily) to nine healthy male subjects, aged 24-35 yr. B-Cell function was assessed by measuring the acute insulin response (AIR) to glucose (AIRglucose) at fasting glucose and to arginine (AIRarg) at glucose concentrations of fasting, approximately 14 and more than 28 mM after 2 (n = 7) and 8 days (n = 9) of octreotide. The AIRarg at more than 28 mM glucose (AIR500) is an estimate of B cell secretory capacity, while the glucose level at which 50% of AIR500 occurs is termed PG50 and can provide an estimate of B-cell glucose sensitivity. Insulin sensitivity and the parameters describing glucose disposal were measured using Bergman's minimal model. Octreotide administration resulted in the development of mild fasting hyperglycemia, marked fasting hypoinsulinemia, as well as a marked reduction in AIRglucose [mean +/- SE; pretreatment, 260 +/- 48 pM; 1 day, 62 +/- 14 pM (P less than 0.005 vs. pretreatment); 8 days, 62 +/- 7 pM (P less than 0.005 vs. pretreatment)]. In addition, there was an associated marked reduction in iv glucose tolerance. While the AIRarg at fasting glucose (pretreatment, 233 +/- 27 pM; 2 days, 144 +/- 27 pM; 8 days 281 +/- 55 pM) and AIR500 (pretreatment 1000 +/- 178 pM; 2 days, 651 +/- 82 pM; 8 days, 1041 +/- 219 pM) remained unchanged, the AIRarg at 14 mM decreased significantly during octreotide [pretreatment 986 +/- 178 pM; 2 days, 363 +/- 62 pM (P less than 0.001 vs. pretreatment); 8 days, 623 +/- 130 pM (P less than 0.005 vs. pretreatment)], resulting in a rightward shift of the dose-response curve such that the estimated PG50 increased from 8.8 +/- 0.6 to 12.9 +/- 1.3 mM (P less than 0.05) after 2 days and was maintained for 8 days (11.2 +/- 0.8 mM; P less than 0.05 vs. pretreatment). Despite the development of marked insulin deficiency, the insulin sensitivity index (SI) did not change significantly (pretreatment, 11.34 +/- 1.59 x 10(-5); 1 day, 10.01 +/- 2.28 x 10(-5); 7 days, 9.65 +/- 1.69 x 10(-5) min 1/pM).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2205633 TI - Early clinical pathologists. 2. Thomas Hodgkin: pathologist, physician, and philanthropist. PMID- 2205632 TI - Striated muscle tropomyosin-enriched microfilaments of developing muscles of chicken embryos. AB - The striated muscle tropomyosin-enriched microfilaments were isolated from developing muscles in ovo by the previously described method with a monoclonal antibody against striated muscle isoforms of tropomyosin (Lin & Lin, 1986). Two dimensional gel analysis of the isolated microfilaments from developing heart, thigh and breast muscles revealed the coexistence of non-muscle isoforms of tropomyosin and actin throughout all stages of embryogenesis. A small but significant amount of skeletal muscle isoforms (alpha, beta) of tropomyosins and their phosphorylated forms was detected in the microfilaments isolated from hearts of 6-15-day-old embryos. These skeletal isoforms of tropomyosins disappeared after this stage of embryogenesis. In addition, we also detected both embryonic and adult isoforms of troponin T in early developing hearts. In developing thigh and breast muscles, the presence of non-muscle tropomyosin isoforms 2, 3a and 3b in the isolated microfilaments was apparent. The contents of tropomyosin isoform 2 were decreased with development and this non-muscle isoform completely disappeared at the 15th day of embryogenesis. On the other hand, the non-muscle tropomyosin isoforms 3a and 3b were present throughout all stages of development. Double-label immunofluorescence microscopy with monoclonal CH1 (anti-striated muscle isoforms of tropomyosin) and CG beta 6 (anti-non-muscle isoforms of tropomyosin) on the isolated, glycerinated skeletal and cardiac muscle cells of 10-day-old or 13-day-old embryos confirmed the colocalization of muscle and non-muscle isoforms of tropomyosins within the same cells. These results suggest that different isoforms of actin and tropomyosin can assemble into a class of microfilaments (i.e. striated muscle tropomyosin-enriched microfilaments) in ovo, which may transform into the thin filaments of mature muscle cells. PMID- 2205634 TI - Immunoalkaline phosphatase technique applied to paraffin wax embedded tissues in diagnostic renal pathology. AB - An indirect immunoalkaline phosphatase (IAP) technique was used to evaluate the glomerular deposition of immunoglobulins, C3, C1q and fibrinogen. In 80 renal biopsy specimens the results obtained using this technique were compared with those obtained by direct immunofluorescence to see if it could be used as a viable alternative. The IAP technique was straightforward to perform, it yielded quick results, and was highly reproducible, provided that a standardised short fixation period of two and a half hours was used. For the detection of immunoglobulin deposits, the IAP results correlated well with those of immunofluorescence. Despite poorer performance in identifying complement components and fibrinogen it could, within certain limits, provide an adequate diagnostic alternative to immunofluorescence. Each technique gave false negative results, those of immunofluorescence being related to its failure to identify mesangial deposition of IgA in two cases where its distribution seemed to be focal, and those of IAP to a failure to detect linear deposition of IgG in all three cases of anti-glomerular basement membrane disease. PMID- 2205635 TI - Betaxolol: a new long-acting beta 1-selective adrenergic blocker. AB - Betaxolol (Searle, Skokie, Illinois) is a new beta 1-selective adrenergic blocker with no partial agonist action and minimal membrane stabilizing activity. Its pharmacokinetic profile is characterized by a long serum half-life and excellent oral bioavailability, with little first-pass metabolism. The mean 16-hour half life of betaxolol has been shown to provide full 24-hour control of blood pressure and heart rate. Betaxolol has been proven to be a safe and effective antihypertensive agent, and was recently approved for clinical use in the United States for this indication. PMID- 2205636 TI - Noninvasive blood pressure monitoring at the finger for studying short lasting pressor responses in man. AB - The study of vasoactive agents in man often requires accurate measurement of short-lasting changes in blood pressure. Using a noninvasive photoplethysmographic device (Finapres), the authors investigated in normotensive subjects whether rapid increases in blood pressure can be assessed precisely by monitoring finger blood pressure continuously. Six volunteers were studied on two consecutive days. On the first day, increasing doses of angiotensin I were injected intravenously with the aim to find a test dose which raised systolic blood pressure by 25 to 40 mm Hg. After oral administration of a placebo, the same test dose was injected repeatedly over the next 24 hours. On the second day, the subjects took either 6.25 (n = 3) or 25 mg (n = 3) captopril PO and the serial administration of the test dose of angiotensin I was continued for the next 4 hours. After placebo intake there was a good reproducibility of the blood pressure response to angiotensin I with a coefficient of variation of 15 +/- 4.5% (Mean +/- SD, n = 6). Captopril caused a dose-dependent inhibition of the pressor effect of angiotensin I. These data indicate that noninvasive blood pressure monitoring at the finger represents a useful tool to study short-lasting blood pressure changes produced by vasoactive agents in man. PMID- 2205637 TI - Accuracy in radiographic diagnosis: Dutch practitioners and dental caries. AB - The effective diagnostic accuracy of dentists is the missing link in models for calculating the optimal frequency for radiographic recall. The purpose of this study was to describe the accuracy of Dutch general dental practitioners using bitewing radiographs for the diagnosis and treatment of approximal caries in dentine. Practitioners from a 10 per cent (n = 444) national random sample were sent a set of simulated bitewings, a patient description and a diagnostic response form. The radiographs showed tooth surfaces with (n = 45) and without (n = 60) dentine caries. Microradiography of the sectioned teeth was used as a diagnostic reference standard. The participants were asked to diagnose dentine caries using a five-point certainty scale and decide if restorative treatment was indicated. The response was 62 per cent (n = 276). The area under a mean receiver operating characteristic curve for the practitioners was 88 per cent of the area representing optimal accuracy. Diagnostic accuracy, however, varied considerably between dentists. For caries considered to be 'probably' in the dentine mean sensitivity was 54 per cent (s.d. 14 per cent) and specificity was 97 per cent (s.d. 5 per cent). The pooled restorative treatment decisions of the dentists had a mean sensitivity of 62 per cent and a specificity of 96 per cent. More surfaces were considered in need of treatment than were diagnosed as 'probably' having dentine caries. Treatment decisions were more accurate than diagnostic ability might indicate. Paradoxically this may be because errors in visual ability were partly compensated for by 'over treatment' decisions. PMID- 2205638 TI - Effect of fatigue upon the interfacial bond strength of repaired composite resins. AB - A comparative study of the fatigue limits of repaired samples of three composite resins was undertaken using the staircase technique. Following storage in water for 21 days at 23 degrees C the surfaces of the specimens to be bonded were ground with a fine Soflex disc, washed and dried. The surface was treated with either Scotchbond or a silane coupling agent, or left untreated, and a composite repair of the same material added. The specimens were thermally cycled and tested sequentially for 5000 cycles at different stress instruments using a transverse impact load. A statistically valid value for mean fatigue limit was determined for each design. This showed that resistance to fatigue forces was lower in repaired specimens than in complete specimens. The use of Scotchbond Dual Cure bonding agent gave the strongest repair. PMID- 2205639 TI - [The marine bacterium Alteromonas piscicida--a producer of enzymes with thrombolytic action]. AB - The ability of marine bacteria A. piscicida to produce exoproteases that were able to lyse human blood clots has been studied. Optimal conditions for biosynthesis of these enzymes have been found. The enzyme has been partially purified. In concentration of 1 mg/ml it has activity corresponding to that of 500 micrograms/l plasmine and 100 micrograms/ml trypsine. The enzyme activity was completely inhibited after incubation in human blood plasma. PMID- 2205640 TI - Etching times. PMID- 2205641 TI - Multicenter clinical trial of ibuprofen and acetaminophen in the treatment of postoperative dental pain. AB - Pharmacological management of pain for acute and chronic conditions has been guided by a scientific understanding of peripheral and central acting mechanisms for the control of inflammation as well as pain. Oral surgery pain is a reliable model to reference the effectiveness of commonly used analgesics such as ibuprofen and acetaminophen. A total of 706 patients who were experiencing moderate to severe pain received a single dose of ibuprofen, acetaminophen, or placebo. After 6 hours, the degree of pain relief and tolerance was assessed. Ibuprofen has important implications for postoperative pain in clinical practice. PMID- 2205643 TI - Coverage of the denuded root surface using the free soft tissue autograft. AB - This paper presents a new soft tissue graft technique that allows the surgeon not only to increase the zone of attached gingiva, but also to cover previously denuded root surfaces. Predictability of the procedure is discussed and the results are related to the health of the periodontium and to the patient's self image. PMID- 2205642 TI - The effects of resin-bonded and conventional fixed partial dentures on the periodontium: restoration type evaluated. AB - The purpose of this study was to compare the long-term and short-term periodontal response to three different modalities of fixed prosthodontic tooth replacement. Posterior proximal sites adjacent to abutment teeth supporting etched metal and two designs of conventional fixed partial dentures (FPDs) were assessed 6 months to 5 years after insertion. For the long-term observation, the etched metal resin bonded FPDs had significantly greater plaque scores than both of the conventional designs. The resin-bonded FPD group had statistically, but not clinically, significant increased probing depths than the supragingival FPD group. In spite of the increased levels of supragingival plaque associated with the etched metal FPD, this type of fixed prosthesis was no more injurious to the periodontium than the subgingival conventional FPD designs. PMID- 2205644 TI - Oral galvanism in Sweden. AB - Although a questionnaire response showed that many Swedes are concerned about oral galvanism, it seems that the symptoms changed as each theory was challenged. The symptoms changed with additional knowledge of the patient and the environment. PMID- 2205646 TI - "Greedy kisses" and "Melting extasy": notes on the homosexual world of early 18th century England as found in Love Letters Between a Certain Late Nobleman and the Famous Mr. Wilson. PMID- 2205645 TI - Selective staining of nucleic acids by osmium-ammine complex in thin sections from lowicryl-embedded samples. AB - Osmium-ammine (OA)/SO2 selectively contrasted RNA- and DNA-containing structures in thin sections from Lowicryl-embedded samples. No cell structures were stained after Epon embedding. RNAse and DNAse digestion experiments demonstrated that only RNA and DNA were stained in Lowicryl thin sections. Protease digestion did not modify the staining reaction. The very fine end-reaction produced a very high resolution of the stained structures. The staining reaction was not due to the presence of SO2 but to the low pH of the solution (ranging from 1.5-2.2). OA in glycine buffer, pH 1.5, selectively contrasted nucleic acids. Electrostatic bonds between nucleic acids and OA complex were probably involved in the staining reaction. Increasing the pH value of the staining medium resulted in loss of OA specificity for nucleic acids. The high electrolyte concentration of the staining medium hindered the staining reaction. PMID- 2205648 TI - Love Letters Between a Certain Late Nobleman and the Famous Mr. Wilson. PMID- 2205647 TI - Sodomy transformed: aristocratic libertinage, public reputation and the gender revolution of the 18th century. PMID- 2205650 TI - The socio-sexual milieu of the Love-Letters. PMID- 2205649 TI - An introduction to the Love-Letters: circumstances of publication, context, and cultural commentary. PMID- 2205651 TI - Prevalence of anti-group B streptococcal type III capsular IgG antibodies in the United Kingdom and an analysis of their specific IgG subclasses. AB - Neonatal infection due to group B streptococcus (GBS) has a higher incidence in the USA than in the United Kingdom. A British population was investigated to ascertain the proportion of women who have protective anti-GBS type III IgG levels. Thirty-one (34%) of 90 pregnant women, 10 (43%) of 23 nonpregnant women, and 5 (50%) of 10 mothers of healthy colonized infants had anti-type III IgG greater than or equal to 2 micrograms/ml. Of 19 mothers who had infants infected with GBS type III, 17 (89%) had low specific IgG levels; of the other 2, the infants themselves had low IgG levels. The proportion of women in the UK with protective antibody levels is higher than in the USA. Sera (12) were assayed for anti-type III IgG isotypes; all contained IgG2, 6 had detectable IgG1, and 1 had IgG4. PMID- 2205652 TI - Differential human serologic response to two 60,000 molecular weight Chlamydia trachomatis antigens. AB - Chlamydia trachomatis causes sexually transmitted diseases and is associated with serious long-term sequelae such as tubal infertility and ectopic pregnancy. There have been suggestions that chlamydial antigens of approximately 57,000-60,000 Mr may be involved in the immunopathology. Two important chlamydial antigens of 57,000-60,000 Mr are a Triton X-100-soluble antigen, which induces hypersensitivity in ocular models, and a sarcosyl-insoluble cysteine-rich structural protein, omp2. In this study, a 57,000 Mr Triton X-100-soluble protein was characterized as the chlamydial homolog of groEL, a heat shock protein. Using protein fractions, antibody responses of pelvic inflammatory disease (PID) and ectopic pregnancy patients to chlamydial groEL and omp2 were differentiated. Nearly all patients in both groups were reactive to omp2. Of those with titers greater than or equal to 1:512, 31% of PID sera and 81% of ectopic pregnancy sera were positive for chlamydial groEL (P = .004). This selectivity suggests that women with PID who develop chronic sequelae are those with antibody to groEL. PMID- 2205653 TI - An immunogenic 30-kDa surface antigen of pathogenic clinical isolates of Entamoeba histolytica. AB - A 30-kDa surface antigen was identified by Western blots with human immune sera in all 15 isolates of E. histolytica from patients with invasive amebiasis (pathogenic) but not in 15 strains from asymptomatic patients (nonpathogenic). This antigen is highly immunogenic in naturally infected humans and was recognized by sera from 22 patients with invasive disease but not by sera from 13 patients harboring nonpathogenic strains. Its surface location is supported by its differential extraction in the detergent phase of Triton X-114 and by surface immunofluorescence of live trophozoites. Unlike previously described amebic surface antigens, this 30-kDa antigen is undetectable in axenic strains that were originally isolated from patients with invasive disease but have been adapted to grow without bacteria. Affinity-purified antibody to the 30-kDa antigen did not promote lysis of complement-resistant pathogenic strains. This surface antigen may be diagnostically important in the identification of pathogenic clinical isolates. PMID- 2205654 TI - Special considerations for managing suspected human immunodeficiency virus infection and AIDS in patients from developing countries. PMID- 2205655 TI - Use of paper-absorbed fingerstick blood samples for studies of antibody to human immunodeficiency virus type 1 in intravenous drug users. AB - The suitability of paper-absorbed (PA) fingerstick blood specimens for antibody testing of human immunodeficiency virus type 1 (HIV-1) was examined in two populations of intravenous drug users (IVDU): 393 persons from a drop-in counseling and testing clinic and 145 from a methadone treatment clinic. From the first group, the same 66 immunoblot-confirmed enzyme immunoassay (EIA)-positive specimens were identified in sera from venipuncture and parallel fingerstick PA specimens. The latter had slightly higher EIA mean background levels resulting in 10 immunoblot-negative EIA-positive samples versus 6 in the sera group. HIV-1 seroprevalence was 17% of 393 from the drop-in clinic. By category of IVDU, the rates were 34% and 14% for active and recovering IVDU, respectively (P less than .001), and 36% in black and Latino compared with 13% in white IVDU (P less than .002). Of the 145 participants in the methadone program, 39% had antibody to HIV 1: 49% for blacks and Latinos compared with 30% in whites (P less than .01). The data indicate that antibody testing for HIV-1 by PA is equivalent to the serum antibody assay of venipuncture specimens. The fingerstick method appears to have greater use for serosurveys and screening programs because of convenience, safety, and ease of storage, transport, and processing of samples. PMID- 2205656 TI - Age-specific prevalence of antibody to enterotoxigenic Escherichia coli in Ecuadorian and German children. AB - Serum samples from 1397 Ecuadorian children 0-5 years of age were tested by ELISA for antibodies to enterotoxigenic Escherichia coli (ETEC). A gradual prevalence and titer increase was seen for IgG antibodies to heat-labile enterotoxin in children 6-18 months old; 90% prevalences were reached in the second year of life. At this age less than 10% of West German children showed IgG antibodies to heat-labile enterotoxin. In Ecuador age-related ETEC-specific antibody titer increases correlated with age-related prevalence of diarrheal disease. On the other hand, pooled lipopolysaccharide from different ETEC-associated O serogroups could not be used as a seroepidemiologic marker of ETEC infections. PMID- 2205658 TI - Beta-lactam-resistant Enterobacter bacteremia in febrile neutropenic patients receiving monotherapy. AB - Bacteremia with resistant Enterobacter species has been reported in febrile, neutropenic cancer patients receiving beta-lactam antibiotics. To assess the relationship between enterobacter bacteremia and ceftazidime monotherapy, medical records were reviewed and isolates were tested from 16 neutropenic and 35 nonneutropenic patients with Enterobacter bacteremia. Fifteen isolates from the neutropenic patients were resistant to extended spectrum cephalosporins; only 12 of 35 isolates from the nonneutropenic patients were resistant to Enterobacter species. The neutropenic patients also had more beta-lactam therapy, both immediately before bacteremia and in the preceding year, than did nonneutropenic patients. Prior beta-lactam antibiotic exposure may predispose neutropenic patients to develop resistant Enterobacter bacteremia. PMID- 2205657 TI - Prevention of Escherichia coli K1 bacteremia in newborn mice by using topical vaginal carbohydrates. AB - Pregnant Swiss-Webster mice were vaginally inoculated with 5 x 10(4) Escherichia coli K1 strain LH (O75:K1:H3) or C94 (O7:K1:H-). Inhibitor solutions were applied vaginally before delivery and the incidence of bacteremia and surface colonization determined in neonates at 3 days of age. E. coli K1 strain LH resulted in bacteremia in 77% and colonization in 74% of control newborn mice. After topical maternal vaginal D-mannose treatment, bacteremia and colonization were present in 25% of neonates. Topical vaginal application of subinhibitory concentration of gentamicin reduced bacteremia to 23% of neonates. Topical methyl alpha-D-mannoside and p-nitrophenyl-D-mannoside, however, prevented bacteremia in 100% of newborn mice. A neonatal meningitis strain of E. coli K1 (C94) caused bacteremia in 100% of neonates and was also completely inhibited by methyl-alpha D-mannoside. This technique of vaginal treatment before delivery may have applicability to human mothers and their infants. PMID- 2205659 TI - Polyploidy in differentiation and evolution. AB - Somatic and generative (germ-line) polyploidy are more widely spread phenomena among living organisms than generally thought. The occurrence of polyploidization and related events in normal and pathological differentiation, their recognized main functions, as well as the structural specificities of polyploid nuclei are reviewed, and the relationship between ontogenetic and phylogenetic events is discussed. The mechanisms leading to the polyploid state, as well as other processes resulting in a genomic condition different from the diploid one (such as DNA under-replication, gene amplification, and chromatin elimination), are briefly sketched. The various changes in chromosomal DNA described are, in conclusion, seen as evidence supporting the paradigm of a "fluid" or dynamic organization of the eukaryotic genome, as being part of a cybernetic feedback regulation system of gene expression. A model is proposed that unifies the aspects of DNA variation, chromatin structure, and diversification in ontogenesis and phylogenesis. PMID- 2205660 TI - Megakaryocyte endomitosis: a review. AB - During the early stages of their differentiation, megakaryocytes become polyploid through repeated DNA replication and endomitotic cycles without cytokinesis. The molecular basis for the process of polyploidization remains unknown. This review summarizes available information on the cell biology of the process of endomitosis. PMID- 2205661 TI - Regulation of human megakaryocytopoiesis: analysis of proliferation, ploidy and maturation in liquid cultures. AB - A liquid culture technique associated with either double staining and flow cytometry or electron microscopy was used to study human megakaryocytopoiesis. During development from the embryo to the adult, a progressive increase in ploidy classes associated with an enhancement of megakaryocyte (meg) size was observed. Granulocyte-macrophage colony-stimulating factor had no effects on adult marrow cultures. In contrast, interleukin (IL) 3 induced a marked proliferation, but was unable to promote polyploidization. Furthermore, it abrogated the effects on endomitosis of aplastic plasma (AP). This negative effect on polyploidization of IL-3 could be partially dissociated from its effects on proliferation by a delayed addition in culture. AP acted on both proliferation and endoreplication, which was not due to the main hematopoietic growth factors, including IL-6. A synthesis of IL-6 was detected by in situ hybridization in cultured cells including megs which also express receptors for IL-6. These results suggest that terminal meg differentiation may be regulated by an autocrine IL-6 loop, and that megakaryocytopoiesis may be independently regulated at early and late stages of differentiation. PMID- 2205663 TI - Genetic and physiological variations in megakaryocyte DNA content distributions. AB - The DNA content of normal megakaryocytes usually ranges from 8N to 64N, with 16N as the modal DNA content. The frequency of cells at each DNA content can be altered by experimental induction of thrombocytopenia, thrombocytosis or marrow ablation, and in various disease states; however, the mechanisms and regulation involved in the process of polyploidization remain obscure. This discussion will focus on genetic and physiologic variations in megakaryocyte DNA content distributions. The genetic variations are those we have observed among mouse strains, with the most pronounced present in several C3H substrains in which the modal megakaryocyte DNA content is 32N, rather than 16N. The physiologic variation reported here is a shift to the right in megakaryocyte DNA content distributions during late pregnancy in the rat. PMID- 2205662 TI - The effect of cytokines on the ploidy of megakaryocytes. AB - The effects of recombinant cytokines on the ploidy of human megakaryocytes derived from megakaryocyte progenitors were studied using serum-free agar cultures. Nonadherent and T cell-depleted marrow cells were cultured for 14 days. Megakaryocyte colonies were identified in situ by the alkaline phosphatase anti alkaline phosphatase technique, using monoclonal antibody against platelet IIb/IIIa. The ploidy of individual megakaryocytes in colonies was determined by microfluorometry with DAPI (4',6-diamidino-2-phenylindole) staining. Recombinant human interleukin 3 (rhIL-3) and recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) supported megakaryocyte colony formation in a dose dependent manner. However, both rhIL-3 and rhGM-CSF had no definite ability to increase the ploidy values. Recombinant human erythropoietin (rhEpo) or recombinant human macrophage colony-stimulating factor (rhM-CSF) by itself did not stimulate the growth of megakaryocyte progenitors. rhEpo or rhM-CSF, however, stimulated increases in the number, size and ploidy values of megakaryocyte colonies in the presence of rhIL-3 or rhGM-CSF. Recombinant human interleukin 6 (rhIL-6) showed no capacity to generate or enhance megakaryocyte colony formation when added to the culture alone or in combination with rhIL-3. rhIL-6, however, increased the ploidy values in colonies when added with rhIL-3. These results show that rhEpo, rhM-CSF and rhIL-6 affect endomitosis and that two factors are required for megakaryocyte development. PMID- 2205664 TI - Molecular regulation of human megakaryocyte development. AB - Extracellular regulators of human megakaryocyte development are becoming better defined. How these regulators function at the subcellular and, in particular, the molecular levels remains almost completely unknown. The recent development of molecular micromethodologies such as in situ hybridization, the polymerase chain reaction, and the use of antisense oligodeoxynucleotides now make such studies possible in normal cells. We therefore examined the effect of several recombinant human hematopoietic growth factors and the maturation agonist phorbol myristate acetate on the expression of selected growth-regulated and maturation/function related genes. We also examined the role of the c-myb proto-oncogene in regulating megakaryocyte proliferative activity and ploidy development. Our results demonstrate that growth factors have complex time and concentration effects on gene expression in morphologically recognizable human megakaryocytes. They also suggest that a more complete understanding of normal megakaryocyte development at the molecular level will soon be possible. PMID- 2205665 TI - A biological and computational model of megakaryocyte development as a stochastic branching process. AB - The purpose of this paper is to describe a model of megakaryocytopoiesis as a branching process with stochastic processes regulating critical control points of differentiation along the stem cell megakaryocyte platelet axis. Progress of cells through these critical control points are regulated by transitional probabilities, which in turn are regulated by influences such as growth factors. The critical control points include transition of resting megakaryocytic stem cells (CFU-meg) into proliferating stem cells, the cessation of cytokinesis, and the cessation of DNA synthesis. A computerized computational method has been developed for directly fitting the stochastic branching model to colony growth data. The computational model has allowed transitional probabilities to be derived from colony size data. The model provides a unifying explanation for much of the heterogeneity of stages of maturation within populations of megakaryocytes and is fully compatible with historical data supporting the stochastic nature of hematopoietic stem cell regulation and with modern molecular concepts about control of the cell cycle. PMID- 2205667 TI - Megakaryocyte polyploidy as a grouped geometric distribution obeying the log normal population law. AB - Discrete nuclear lobe scores and flow- or image-cytometry DNA values of classically identified megakaryocytes behave as a grouped geometric distribution. This model is fully specified by a geometric mean and standard deviation (GM and GSD), the latter typically being ca 1.16 for volumes of diploid blood cell populations. Via log-normal probability paper, the 30 to 50 megakaryocytes in clinical marrow smears readily yield the ploidy model's GM and GSD which are named MPM and MPD for megakaryocyte polyploidy median and dispersion. In euthrombopoietic outbred mammals, MPMs are ca 12N ploidy units, and MPDs approximate a factor of 1.41. Both are unitless criteria. Thus, the thrombon is characterized by three populations exhibiting the high size dispersion which unmasks canonical operation of the log-normal population law: picoliter megakaryothrombocytes with their MPD ca 1.41, femtoliter thrombocytes with a volume GSD ca 1.74, and the end product of locally delivered pieces of subattoliter platelet dust with a volume GSD ca. 2.0. PMID- 2205666 TI - The control of megakaryocyte ploidy and platelet production: biology and pathology. AB - Following experimental platelet destruction in animals, large platelets, which are more hemostatically active, are produced before any change in bone marrow megakaryocyte DNA content. When platelet production is stimulated by administration of i.v. vincristine in rats, megakaryocyte ploidy is increased, but mean platelet volume is unchanged. When platelet production and destruction are both stimulated by chronic hypoxia or administration of anti-platelet serum, mean platelet volume and megakaryocyte DNA content are both increased. Since platelet volume is determined primarily at thrombopoiesis, these results imply that mean platelet volume and megakaryocyte DNA content are under separate hormonal control. Therefore, it has been postulated that changes in mean platelet volume occur following changes in platelet production rate, whereas changes in megakaryocyte ploidy are associated with an increased rate of platelet production. In myocardial infarction, platelets have increased mean volume and reduced bleeding time more than in controls. In addition, men with myocardial infarction have increased megakaryocyte size and increased DNA content when compared to controls. These changes are similar to those observed in rabbits following cholesterol feeding. If megakaryocyte polyploidy and mean platelet volume are under separate hormonal control, this suggests that in myocardial infarction, both hormones are active--one stimulating an increased platelet size, the other stimulating the increased megakaryocyte DNA content. In contrast, patients with lymphoma exhibiting a secondary thrombocytosis have no change in mean platelet volume. However, these subjects also have larger bone marrow megakaryocytes when compared to controls. The relation between megakaryocyte size and ploidy implies that the DNA content of these cells is increased in lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2205668 TI - [The causative agent from a patient with spotted fever group rickettsiosis in Japan on Awaji Island, Hyogo]. AB - Misaka strain was isolated as the causative agent from a patient with spotted fever group rickettsiosis in Japan by using nude mice on Awaji Island, Hyogo in September 1988. The nude mice infected with the isolate showed weakness and splenomegaly and died in two or three weeks after the infection. The cyclophosphamide-treated mice infected with the isolate died between four and seven days after the infection. The infected normal mice recovered and acquired immunity. The infected adult male guinea pigs were feverish and showed swelling and redness of the scrotum between two and eight days after the infection, and recovered. The Misaka strain was propagated well in Vero cells in tissue culture. The rickettsial particles were seen as diplobacillary and diplococcal forms growing predominantly in the cytoplasm and occasionally in the nucleus of infected cells. The serological characteristics of the Misaka strain were analyzed by the cross-immunofluorescent antibody method. The Misaka strain, the Katayama strain first isolated in Tokushima in 1987, and the representative strains of spotted fever group rickettsiae in the world; R. rickettsii Smith, R. sibirica 246, R. conorii Moroccan, R. akari MK (Kaplan), R. australis Phillips, R. montana Tick and Thai TT-118 strains were used as antigens. And immune mouse serum samples against the Misaka, Katayama, 246, Phillips and TT-118 strains were used as antisera. The result revealed that these strains showed cross-reaction and share a common antigen of spotted fever group rickettsiae. Furthermore, it became obvious that the Misaka strain and the Katayama strain have the same serotype-specific antigen different from the strains of other spotted fever group rickettsiae using Anti-Katayama monoclonal antibodies. PMID- 2205669 TI - [Isolation of group A streptococci from pharyngitis patients of all ages--studies from the clinical and epidemiological standpoint]. AB - During the period from June 1981 through Dec. 1985, isolation of group A streptococci was attempted from throat swabs of pharyngitis patients of all ages, who visited a clinic in the central area of Yokohama-city. The data were analysed clinically and epidemiologically. The results were summarized as follows. 1) Group A streptococci were isolated from 85 (30.5%) out of 279 patients with pharyngitis. This is almost within the range of other reports. 2) During one year in the study period, no isolates of group A streptococci were obtained from throat swabs of 32 controls (healthy persons working in the clinic or patients without pharyngitis). 3) The isolation rate correlated with the presence of pharyngeal purulent exudate and also with high maximum body temperature after onset of the illness. The isolation rate was significantly higher in patients with these two signs than those without them. Therefore, these two signs are useful to predict group A streptococcal pharyngitis prior to laboratory examinations. 4) The isolation rate was high in the age groups under 10 and from 30 to 39. 5) The isolation rate was high in winter and low in summer. 6) The typing test revealed T types 13, 28 and 4 to be relatively frequent isolates. PMID- 2205670 TI - [Comparison of D-arabinitol, candida antigen, and beta-glucan, measured by the chromogenic limulus assay, in the rabbit model of systemic candidiasis]. AB - In this study, we measured D-arabinitol, candida antigen and beta-glucan in the rabbit model of systemic candidiasis. It was recently reported that the factor G, one of the coagulation enzymes from the horseshoe crad amebocyte lysate, reacts with beta-glucan or polysaccharide from fungus, and not with endotoxin. The newly developed endotoxin specific chromogenic Limulus assay (endospecy test), which is devoid of factor G, did not react with any rabbit serum. But the beta-glucan measured by the conventional Limulus assay (toxicolor test), which contains the factor G, was elevated (from 10 pg/ml to 100 pg/ml) in all cases of rabbit model of system candidiasis. Serum D-arabinitol, measured by Sone's enzymatic fluorometric method, increased in all cases, but Cand-Tec (candida detection system by latex agglutination) showed only one positive case in five innoculated rabbits. PMID- 2205671 TI - [Clinical evaluation of antimalarial drugs]. AB - We have analyzed the clinical data of 189 patients with malaria to establish antimalarial regimens in Japan. The causative parasite species were Plasmodium falciparum in 56 cases (30%), P. vivax in 132 (70%) and P. malariae in 1 (1%). The outcomes f malaria cases are as follows: Cure rats in falciparum and vivax malaria are 86% and 91%, respectively. Two patients died of falciparum malaria and recurrence occurred in 6 cases (11%) of falciparum malaria. Relapse was seen in 12 (9%) of vivax malaria. Chloroquine was most frequently used among antimalarial agents (in 123 cases, 65% of the total) for suppressing acute attacks. The efficacy of chloroquine was evaluated by classifying each case into three groups: chloroquine alone in group one, chloroquine in combination with other antimalarials in group two and other antimalarials except chloroquine in group three. The cure rate among each group is about 80% and there is no difference among them. However, it is noticeable that recurrence occurred when patients were treated with a combination of chloroquine and quinine. We have found a similar result as this in another old report in Japan. Primaquine is effective for eliminating hepatic tissue schizonts but in this study, relapse occurred in 12 cases of vivax, although primaquine had been used in 10 out of 12 cases. In primaquine group, relapse occurred at a similar rate between chloroquine and Fansidar cases. Further studies are needed to decide whether a larger dose of primaquine is appropriate for treatment of vivax malaria. Recovery periods from fever and parasitemia were compared between chloroquine and Fansidar cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2205672 TI - [O5-antigenic classification of Salmonella typhimurium isolated from outbreaks of Salmonella enteritis]. AB - S. typhimurium (STM) were isolated from outbreaks of Salmonella enteritis and were studied for their reactivity to monoclonal antibody TMY1 specific for Salmonella O5-antigen with the following results; By using the bacterial agglutination test with TMY1, STM were classified into O5-antigenic molecule positive and negative (copenhagen type) strains, suggesting the usefulness of TMY1 as an exquisite epidemiologic tool for Salmonella enteritis. PMID- 2205674 TI - [A case of shigellosis due to Shigella dysenteriae 1 which was thought to be infected in domestic area]. AB - A 43-year-old man was admitted to our hospital because of bloody diarrhea and abdominal pain on January 10, 1989. On laboratory examination S. dysenteriae 1 was isolated from his stool, therefore he was diagnosed as shigellosis. After the administration of ofloxacin was started, S. dysenteriae 1 was immediately eradicated. But his diarrhea persisted until the 19th day from the onset of the illness and his abdominal pain persisted until the 21st day. He had never been overseas and he had never eaten any imported uncooked food recently. Only 14 cases of shigellosis due to S. dysenteriae 1 were found in the last ten years in Japan. All of them were overseas travellers. Although we were not able to determine the source of infection in our case, we inferred that he was primarily infected with S. dysenteriae 1 in Japan. PMID- 2205673 TI - [Biochemical characteristics, growth on selective media, antimicrobial susceptibility, and diarrheagenic toxin production of enteroinvasive Escherichia coli]. AB - A total of 70 strains of enteroinvasive Escherichia coli (EIEC) belonging to 8 different O serogroups including O28ac O29, O121, O124, O136, O143, O144, and O164, was studied for their biochemical characteristics, growth on selective isolation agar, antimicrobial susceptibility, and diarrheagenic toxin production. Among the biochemical characteristics examined, all EIEC strains gave negative lysine decarboxylation and all but one belonging to O124 serogroup, were non motile, regardless of their O serogroups. The one motile O124 strain had a H30 antigen. Some close correlations were also observed between their O serogroups and biochemicals such as utilization of sodium acetate and mucate, ornithine decarboxylation, arginine dihydrolation, gas production from glucose, and lactose fermentation. Among the selective isolation agars, MacConkey and Deoxycholate hydrogen sulfide-lactose (DHL), and modified Shigella-Salmonella (SS) agars supported growth of the EIEC strains well, whereas SS agar was remarkably inhibitory for strains of some O serogroups. Antimicrobial susceptibility was tested for nine drugs including chloramphenicol (CP), tetracycline (TC), streptomycin (SM), kanamycin (KM), ampicillin (ABPC), sulfamethoxazole trimethoprim (ST), nalidixic acid (NA), fosfomycin (FOM) and norfloxacin (NFLX). Forty-one of the 70 strains (58.6%) were found to be resistant to the 6 drugs, such as CP, TC, SM, KM, ABPC or ST. None of the strains were resistant to NA, FOM or NFLX. Among the resistant strains recognized, the strains which showed the resistant patterns of CP.TC.SM.ABPC, CP.TC.SM, TC.SM.ST, TC.SM, and SM appeared to be prevalent. None of the strains gave positive reactions for the production of diarrheagenic toxins of heat-labile enterotoxin, heat-stable enterotoxin, and verocytotoxins 1 and 2. PMID- 2205675 TI - [Cardiac surgery I walked with; a review of the last results of surgery and an analysis of the present status of thoracic surgery in Japan]. PMID- 2205676 TI - [Progress in lung cancer surgery]. PMID- 2205677 TI - [Function of thyroid hormone binding proteins in the cell]. PMID- 2205678 TI - [Leaf senescence and protein degradation]. PMID- 2205679 TI - [Multiple primary cancers associated with gynecologic malignancies]. AB - Seventeen multiple primary cancers including 16 double cancers and one triple cancer were found in 316 patients with gynecologic malignancies who were treated in our department from 1984 to 1988. All pathologic slides but one were reviewed, and cases with possible metastasis or recurrence were not included in this study. The incidence of multiple primary cancers in gynecologic malignancies was 5.4%. Multiple primary cancers were encountered in 4.4% of 205 cervical cancers (including carcinoma in situ), 15.2% of 33 endometrial cancers, and 8.6% of 58 ovarian cancers (including low potential malignancy), respectively. The most frequent sites of other cancers were seen in the large intestine and rectum (5/17), breast (4/17), and gynecologic organs (3/17). Higher incidences were seen in our study that in those in domestic literature. This is probably because detailed anamnesis and gastrointestinal series were obtained in most gynecologic malignancies (especially in endometrial or ovarian cancer). PMID- 2205680 TI - [Significance of twin to twin transfusion syndrome in the prognosis of twin pregnancies and its prenatal diagnosis by ultrasonography]. AB - The reason why TTS worsen the prognosis of twin pregnancies was discussed with reference to case results for perinatal death, and antenatal diagnostic criteria for TTS by ultrasonography was established. Of 12 perinatal deaths in 71 twin pregnancies, eight fetuses were affected with TTS (1 acardia, 4 donors, 3 recipients). Perinatal mortality rate (39.3%), rate of preterm lobar (62.2%), rate of polyhydramnion (50.0%), mean amniotic fluid volume (3.310 ml) and cord cross section area ratio (2.38) in monochorionic discordant twins were higher than in the other three groups (monochorionic concordant twins, dichorionic discordant twins and dichorionic concordant twins). Eight fetuses among 12 monochorionic discordant twins were affected with TTS. All twins which showed a single GS in early pregnancy were monochorionic twins. Therefore TTS was considered to have a poorer prognosis than usually reported for all TTS, and to find monochorionic discordant twins with a high cord cross section area ratio must be the key in the screening of TTS. Antenatal diagnosis of TTS by ultrasonography is summarized as follows: 1) A single GS in early pregnancy. 2) Estimated body weight difference between the twins/estimated body weight of the larger twins greater than or equal to 0.2. 3) Cord cross sectional area ratio greater than or equal to 2.0. PMID- 2205681 TI - Establishment of hybridomas secreting monoclonal antibodies to placental alkaline phosphatase and development of an enzyme immunoassay for its determination. AB - We established seven hybridomas secreting murine IgG monoclonal antibodies (MoAbs) to placental alkaline phosphatase (PLAP). The seven hybridomas were designated (1) 7C6, (2) 6G10, (3) 5B9, (4) 6D5, (5) 6B5, (6) 11G6 and (7) 3E10, respectively. The characteristics of these hybridomas were evaluated by radioimmunoassay (RIA) with 125I-PLAP. Their reactivity with the intestinal alkaline phosphatase, one of the alkaline phosphatase isozymes, was (1) 0.04, (2) 0.2, (3) 1.4, (4) 1.8, (5) 0, (6) 4.0 and (7) 6.2(%), respectively. None of them showed signs of cross-reactivity with the liver-type alkaline phosphatase, also one of the alkaline phosphatase isozymes, within a PLAP concentration of 2,000 IU/l. The subtype of 5B9 was IgG1, and that of the others was IgG2a. We then used 7C6, to develop a sensitive, specific and convenient enzyme immunoassay (EIA) for the determination of PLAP, and assayed sera from patients with various gynecologic diseases. The incidence of increased PLAP was 6.4% in patients with benign diseases, 21.5% in cervical cancer, 36.4% in endometrial carcinoma, and 39.5% in malignant ovarian tumors. The specificity for malignant diseases seemed to be higher than that of CA125. Among endometrial carcinomas, well differentiated adenocarcinoma had the highest incidence of an increased concentration. Among malignant ovarian tumors, serous cystadenocarcinoma, endometrioid carcinoma, dysgerminoma and Krukenberg's tumor showed a higher incidence than the other types. PMID- 2205682 TI - Acid-fast bacilli in semen; correlation with bacterial index. AB - Thirty multibacillary patients (12 LL, 18 BL) were historically reviewed and clinically assessed for evidence of testicular involvement. The bacterial index (BI) of the patients ranged from 1+ to 6+; the morphological index (MI), from 0% to 3%. Nine (30%) patients had oligospermia, while acid-fast bacilli (AFB) were demonstrable in the semen of 3 (10%) patients (2 LL, 1 BL). There was a significant correlation between the BI and the demonstration of AFB in semen (p less than 0.01). PMID- 2205684 TI - Quantitation of IgM antibodies to the M. leprae synthetic disaccharide can predict early bacterial multiplication in leprosy. AB - Quantitative enzyme-linked immunosorbent assays detecting IgM to the soluble Mycobacterium leprae crude sonicate (CD75) and the synthetic disaccharide antigen coupled to bovine serum albumin (ND-BSA) were assessed for their ability to determine early infection in families/household contacts of leprosy patients and employees of a leprosy center working in close contact with leprosy patients. Although IgM to both antigens (CD75 and ND-BSA) correlated with the bacterial index (BI) assessed histologically on skin-biopsy samples, the level of IgM antibodies to ND-BSA was a much more sensitive indicator of low bacterial loads. A 4.4-fold difference in antibody levels was observed between the mean group levels of endemic controls (N = 116) and tuberculoid leprosy patients with a BI of 0 (N = 88), increasing to sevenfold in tuberculoid leprosy patients with a BI of 1 (N = 20). Using a statistical cut off with endemic controls (mean + 2 S.D.), household/family contacts showed 30% seropositivity (N = 180) as compared to staff contacts who showed 17% seropositivity (N = 55). Percent seropositivity in family contacts was not related to the type of leprosy of the index case (lepromatous vs. tuberculoid) or the duration of treatment of the index case. Age of the individual in the family contact group had a significant influence on seropositivity. These results support the hypothesis that, in this community, factors other than the viable bacterial load of the index case, such as genetic susceptibility, may be influencing the high rate of seropositivity in family contacts. IgM ND-BSA antibodies seem to provide a good indicator of low antigenic loads and could prove to be useful in detecting subclinical infection before the onset of disease. Follow-up studies of these seropositive individuals are in progress to understand the relationship between seropositivity and the progress of clinical disease. PMID- 2205683 TI - Operational value of serological measurements in multibacillary leprosy patients: clinical and bacteriological correlates of antibody responses. AB - The antibody responses of 100 previously untreated multibacillary (MB) leprosy patients to one protein and two carbohydrate antigens were examined: 94% of the patients had Mycobacterium leprae-specific antibodies; 89% directed to the species-specific epitope on phenolic glycolipid (PGL-I), 89% against the specific epitope on the 35-kDa protein, and 94% against one or both of the two. By contrast, 67% of the patients had anti-lipoarabinomannan (LAM) antibodies. There were trends for the seropositivity rate and the antibody level to rise with the increasing extent of the disease and as patients moved to the polar lepromatous end of the spectrum. The bacillary load, as measured by the bacterial index, was moderately correlated with the IgM anti-PGL-I and the anti-35-kDa antibody levels and, to a lesser extent, with the IgG antibodies directed at the common mycobacterial carbohydrate LAM. The sensitivity of the IgM anti-PGL-I antibodies for detecting smear-positive MB disease was 91%; that for the anti-35-kDa antibodies was 92%. PMID- 2205685 TI - Sequential monitoring of leprosy patients with serum antibody levels to phenolic glycolipid-I, a synthetic analog of phenolic glycolipid-I, and mycobacterial lipoarabinomannan. AB - Sequential serum samples from leprosy patients at various stages of antibacterial treatment were tested by an ELISA for antibodies to phenolic glycolipid I (PGL I), a synthetic PGL-I analog (ND-BSA), and lipoarabinomannan (LAM) from Mycobacterium tuberculosis to determine if these antibodies could be useful in monitoring response to therapy. Among patients with positive initial anti-PGL-I IgM, a significant decrease in this antibody was seen over time (p less than 0.01), whether assayed by PGL-I or ND-BSA. The two antigens showed good agreement in the detection of decrease in anti-PGL-I IgM. The greatest decrease was seen in patients with a high initial anti-PGL-I IgM and a high bacterial index (BI). Patients with a declining BI were seen to have generally declining antibody levels to PGL-I and to LAM; in those patients with a fluctuating BI, antibody levels were less predictable. We conclude that antibodies to PGL-I and LAM can be useful in following response to therapy in leprosy patients and that either the native PGL-I or ND-BSA can serve as antigen for the ELISA. PMID- 2205686 TI - Assessment of anti-phenolic glycolipid-I IgM levels using an ELISA for detection of M. leprae infection in populations of the South Pacific Islands. AB - Anti-phenolic glycolipid-I (PGL-I) IgM levels were determined in 96% of the general population of the Southern Marquesas and Maupiti, remote islands of French Polynesia, where the average annual detection rates of leprosy during the past 30 years have been 57.1 and 4.4 per 100,000, respectively. The seropositivity in these two areas was 4.3% and 4.2%, respectively. No significant difference (p greater than 0.05) was found between either these two figures or between the percentages of persons with high (greater than or equal to 0.500 OD) anti-PGL-I IgM levels (9.2% and 5.3%). In the two islands, the age distributions of anti-PGL-I IgM were very similar; the percentage of positive responders was higher in females than in males and higher in adolescents than in adults. These results suggest that the usefulness of the determination of anti-PGL-I IgM levels by ELISA, using the synthetic trisaccharide as antigen, for detecting Mycobacterium leprae infection in leprosy control programs is extremely doubtful. PMID- 2205687 TI - Uptake of purine and pyrimidine nucleosides by macrophage-resident Mycobacterium leprae: 3H-adenosine as an indicator of viability and antimicrobial activity. AB - Freshly extracted human- and armadillo-derived Mycobacterium leprae maintained within murine macrophages incorporated significant levels (p less than 0.05 to p less than 0.001) of 3H-adenosine and 3H-hypoxanthine by 6 and 9 days of the culture period. The incorporation of 3H-adenosine was twofold or more higher than 3H-thymidine in 10 out of 15 human-derived M. leprae isolates. Macrophage-adapted bacilli incorporated 10-14-fold higher levels of 3H-adenosine compared to the same bacilli maintained in axenic cultures. The incorporation of these two labels was inhibited by dapsone and rifampin, indicating the utility of in vitro radiometric assays for screening antileprosy drugs and drug sensitivity/resistance in patients. PMID- 2205688 TI - Antigenic protein from Mycobacterium leprae released in macrophages in vitro as indicator of viability of bacteria. AB - Peritoneal macrophages from randombred, Swiss white mice, when cultured and infected with Mycobacterium leprae for 24 hours, are able to show the presence of antigen(s) with binding affinity to antibodies present in the sera of bacteriologically positive, lepromatous leprosy patients. Such antibodies are not seen in sera from normal and healthy persons, tuberculoid leprosy patients, or long-term-treated, bacteriologically negative, lepromatous leprosy patients. The production of the antigen(s) is blocked by the anti-M leprae drug rifampin. Other mycobacteria when incubated with macrophages from mice show very little antigens in the lysate but the antigens have an equal affinity for antibodies in sera from both normal individuals and lepromatous patients. Only the lysates from macrophages exposed to live M. leprae could discriminate and could exhibit differential binding to sera from leprosy patients compared to sera from normal individuals. This antigen(s) does not have any binding ability to the monoclonal antibodies available to the antigens of M. leprae identified at present and shown to be specific to M. leprae. This indicates a separate identity of this product which has potential for further exploitation in exploring host-pathogen interactions related specifically to the leprosy infection and the tolerance of M. leprae inside cells. PMID- 2205690 TI - Leprosy vaccines. PMID- 2205689 TI - Ocular leprosy in nine-banded armadillos following intrastromal inoculation. AB - Leprosy shows a higher percentage of ocular involvement than any other systemic infection. In humans, the cornea is the first ocular tissue affected. Our previous studies in armadillos with naturally acquired and experimental disseminated leprosy showed that 44% had corneal infection. Mycobacterium leprae is found in armadillo burrows in Louisiana, U.S.A., and ocular abrasions may be the portal of entry for these organisms in wild armadillos. To test the cornea as a route of infection, we injected eight armadillos intrastromally with 2 x 10(6) M. leprae in 1 microliters. Two and 4 months later, the armadillos were sacrificed and their eyes processed for light- and electron-microscopy. After 2 months, M. leprae were found in histiocytes mainly in the corneal limbus, sclera and bulbar conjunctiva. At 4 months, however, there was a visible corneal leproma in one animal. Microscopically, it was found to be a histiocytic granuloma with heavy M. leprae invasion. In addition, cells were seen in the anterior chamber. Leprosy is endemic in regions where other corneal infections which compromise the epithelial barrier property are prevalent and where leprosy bacilli are found in the environment. The entry of leprosy bacilli into the cornea may produce lesions which spread posteriorly in the eye. PMID- 2205691 TI - Further comments on leprosy vaccination. PMID- 2205692 TI - Chapman H. Binford, M.D. 1900-1990. PMID- 2205693 TI - [The history of medical engineering instruments development in endodontics]. PMID- 2205694 TI - Effect of positive and negative pressure breathing on sodium and water excretion. AB - Positive and negative pressure breathing purportedly alter renal sodium and water excretion by modifying hemodynamics and/or hormonal regulators of sodium and water homeostasis. To test this hypothesis we monitored hemodynamic and hormonal responses in seven normal men to (1) continuous positive pressure breathing (19 +/- 1 mm Hg for 30 minutes) after water loading (urine volume = 15 +/- 1 ml/min); and (2) continuous negative pressure breathing (11 +/- 1 mm Hg for 30 minutes) after maintenance water ingestion (urine volume = 4 +/- 1 ml/min), in random order. Each study was repeated on a control day without pressure breathing. Results were as follows (mean +/- SE, p less than 0.05): (1) continuous positive pressure breathing decreased urinary sodium from 0.28 +/- 0.07 to 0.17 +/- 0.04 mEq/min, increased atrial natriuretic peptide from 34.2 +/- 4.9 to 48.5 +/- 6.9 pg/ml, and had no effect on osmolar and free water clearances, cardiac output, plasma renin activity, or plasma aldosterone and plasma arginine vasopressin levels; and (2) continuous negative pressure breathing increased free water clearance from 0.6 +/- 0.7 to 4.5 +/- 1.2 ml/min, urine volume from 4.0 +/- 0.8 to 8.9 +/- 1.3 ml/min, and cardiac output from 5.1 +/- 0.4 to 7.0 +/- 0.6 L/min in a proportional manner (r = 0.40, p less than 0.01) and had no effect on osmolar clearance, urinary volumes of sodium and potassium, plasma renin activity, plasma aldosterone, atrial natriuretic peptide, and arginine vasopressin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2205695 TI - Nonazotemic hyperkalemia with renal and extrarenal defects in potassium transport: association with high levels of digoxin-like immunoreactive factor. AB - We report a hypertensive patient with nonazotemic hyperkalemia caused by a combined disturbance in both the internal and external balance of potassium. During a follow-up of 30 months, exacerbations of hyperkalemia were observed, interposed with a return to the previous baseline. Two brief normokalemic periods were recorded. Blood pressure tended to be higher during hyperkalemic peaks. The following findings were detected: (1) hyperchloremic hyperkalemic acidosis with normal glomerular filtration rate, adequately elevated plasma aldosterone levels, and normovolemia; (2) a tubular defect in potassium excretion, refractory to intravenous sodium sulfate (nonreabsorbable anion) and mineralocorticoids; (3) impaired tissue uptake of potassium under insulin administration; (4) exaggerated hyperkalemia following beta-adrenergic blockade and blunted hypokalemic response to a beta-agonist; and (5) a defect in Na/K transport in erythrocytes detected in vitro, coexistent with an elevated level of free digoxin-like immunoreactive factor in serum. These results suggest that our patient had a generalized abnormality in potassium transport. PMID- 2205696 TI - Hepatic steatosis during convalescence from influenza B infection in ferrets with postprandial hyperinsulinemia. AB - The possibility that postprandial hyperinsulinemia could play a role in the development of hepatic lipid disturbances during convalescence from influenza B infection was explored in the ferret as a possible model of the steatosis of Reye's syndrome. Postprandial hyperinsulinemia was produced by feeding young ferrets glucose/water and a regular diet (glucose-treated group), as reflected by the mean serum insulin levels attained, which were 57 and 135 microU/ml during control and postinfluenza periods, respectively. By comparison, ferrets fed water and a regular diet (untreated group) had mean insulin levels of 19 and 22 microU/ml, while postprandial glucose levels were comparable in the two groups of animals for each period. In contrast to untreated animals, grossly visible fatty livers were found in glucose-treated ferrets during convalescence. The total lipid content of these livers had doubled compared with preinfection samples and compared with livers of untreated ferrets. By electron microscopy hepatic mitochondria showed striking changes with diminution of matrix density and reduction in cristae surface area only in convalescent samples from glucose treated animals. Serum free fatty acid (FFA) levels were considerably higher in the glucose-treated animals during fasting before influenza and also after feeding during convalescence. Serum triglyceride (TG) levels were also high during convalescence in the glucose-treated group. Adipose tissue lipoprotein lipase activities were similar between groups, but hormone-sensitive lipase activity was twelvefold higher in glucose-treated ferrets before and after influenza B. These findings indicate that for a given stimulus, glucose-treated ferrets would mobilize more FFA than untreated ferrets. The total capacity for beta-oxidation of FA by the mitochondrial pathway was identical in all groups of animals. Total carnitine palmitoyl transferase (CPT) activity was the same in both control groups, but was significantly diminished in glucose-treated animals during convalescence. As CPT regulates the entry of FA into the mitochondrial matrix, its reduction in response to higher insulin concentrations would limit the oxidation of FA and stimulate TG accumulation. Therefore, the accumulation of lipid in the liver in this model is regarded to have been caused by the simultaneous occurrence of increased lipolysis and increased hepatic TG synthesis owing, in part, to diversion of activated FA by CPT, which is reduced in activity due to the regulatory action of insulin. These findings may have pathophysiologic relevance for the lipid changes that occur in Reye's syndrome and to fatty liver formation in hyperinsulinemic states. PMID- 2205697 TI - A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro. 1956. PMID- 2205698 TI - Louis Daniel Beauperthuy (1807-1871). PMID- 2205699 TI - Dietary influences on serum lipids and lipoproteins. AB - Substantial data are available to indicate that the diet influences serum levels of cholesterol and lipoproteins. These data are derived from studies in laboratory animals, from epidemiologic studies, and from human investigations. Most research has focused on effects of diet on serum total cholesterol concentrations. In recent years, however, attention has shifted to individual lipoproteins, i.e., low density lipoproteins (LDL), high density lipoproteins (HDL), and very low density lipoproteins (VLDL). Three nutritional factors have been identified that raise serum LDL levels; these are saturated fatty acids, cholesterol itself, and excess caloric intake leading to obesity. The major cholesterol-raising saturated fatty acid in the diet is palmitic acid. Several nutrients can be substituted for saturated fatty acids to produce a reduction in LDL-cholesterol levels. These are polyunsaturated fatty acids, monounsaturated fatty acids, carbohydrates, and even one saturated fatty acid, stearic acid. The latter appears to be converted rapidly into a monounsaturated fatty acid in the body. Any of these nutrients can be used for replacement of cholesterol-raising saturated fatty acids in the diet. However, their relative effects on other metabolic processes remain to be determined fully. At present it appears that carbohydrates and monounsaturated fatty acids represent the preferred replacements for saturated fatty acids, although modest increases in polyunsaturated fatty acids and stearic acid, at the expense of cholesterol raising saturates, probably are safe and may provide for greater variety in the diet. PMID- 2205701 TI - The preparation of an ovine monoclonal antibody to progesterone. AB - Peripheral blood mononuclear cells were collected from a sheep immunized against progesterone-11 alpha-hemisuccinate-ovalbumin. Following fusion with NS1 mouse myeloma or heteromyeloma cells, a large number of hybrid colonies was established. These were screened for the production of sheep antibodies to progesterone. Twenty-four cell lines were cloned and one was stabilized. This cell line, O/MP.1A9.D7B2, produced a high-affinity ovine immunoglobulin G1 (dissociation constant 4.8 pmol/l) with a high degree of specificity for progesterone. The antibody was substituted into a competitive enzyme-linked immunosorbent assay for the measurement of progesterone in bovine milk, originally established using an ovine polyclonal antibody, and the results were compared. The monoclonal antibody produced an assay with a lower limit of detection and a greater degree of discrimination than the polyclonal antiserum. PMID- 2205700 TI - Hyperlipoproteinemia type I in a patient with active lipoprotein lipase in adipose tissue and indications of defective transport of the enzyme. AB - This paper presents a case of typical hyperlipoproteinemia type I in a young woman. Her serum triglycerides varied between 2 and 90 mmol/l and she had substantial amounts of apolipoprotein B-48 in fasting plasma. She had no detectable lipoprotein lipase (LPL) activity in post-heparin plasma (less than 0.2 percent of normal). Southern blot analysis suggested no major defect in her LPL gene and Northern blot analysis of adipose tissue RNA showed normal-sized LPL mRNA. A 2-h [35S]methionine incorporation experiment with adipose tissue pieces in vitro showed that she produced normal-sized LPL and had LPL catalytic activity in the tissue. The amounts were, however, only 5-10% of control. No detectable LPL radioactivity or catalytic activity was released from patient tissue even in the presence of heparin in the incubations. Immunofluorescent staining of adipose tissue biopsies from the patient showed LPL immunoreactivity only in adipocytes and little or none within the capillaries. Treatment of immunoprecipitated labeled LPL with endoglycosidase H showed that the oligosaccharide chains on her enzyme were of the high-mannose type and not processed as in controls. Taken together the data suggest that the patient synthesizes a relatively normal LPL protein which is core-glycosylated and folded into active enzyme as in normal subjects, but is not effectively transported via the Golgi to the cell surface. PMID- 2205702 TI - Purification of functional lactotrophs and somatotrophs from female rats using fluorescence-activated cell sorting. AB - As the secretory granules of anterior pituitary cells fuse with the cell surface, there would appear to be sufficient hormone present on the cell surface to be labelled by polyclonal hormone antibodies and thus analysed by flow cytometry. We have therefore applied fluorescence-activated cell sorting to these labelled pituitary cells. Percentage purity and depletion of other cell types was assessed by immunocytochemistry and the reverse haemolytic plaque assay (RHPA). Results demonstrate that fluorescence-activated cell sorting allows almost complete purification of functional lactotrophs and somatotrophs to 96.7 +/- 1.7 (S.E.M.)% and 98 +/- 1.0% respectively by immunocytochemistry, and to 95.8 +/- 1.1% and 97 +/- 0.8% respectively by RHPA. Depletion of other anterior pituitary cell types to less than 2% was demonstrated by both immunocytochemistry and RHPA. Fluorescence-activated cell sorting to this degree of purity was routinely possible with cell yields of 91 +/- 3.4%. To obtain such purity/depletion, it was necessary to use specific antisera of high titre, at concentrations which ensured maximal cell-surface labelling associated with maximal stimulation of hormonal secretion by the appropriate hypothalamic stimulatory factor. Separating cells on the basis of the intensity of prolactin cell-surface labelling demonstrated a low level of binding of the prolactin antibody to gonadotrophs (but not of sufficient fluorescence intensity to be sorted into the prolactin enriched population), raising the possibility of prolactin receptors on gonadotrophs. We were unable to demonstrate the presence of mammosomatotrophs in the normal female rat, since purified lactotrophs did not contain or secrete GH nor did purified somatotrophs contain or secrete prolactin. PMID- 2205703 TI - Uptake of chylomicron remnant retinyl ester via the low density lipoprotein receptor: implications for the role of vitamin A as a possible preventive for some forms of cancer. PMID- 2205704 TI - Comparison of the side-effects of pindolol and atenolol in the treatment of hypertension. AB - A double-blind multicentre study of 349 hypertensive patients was performed to compare the side-effects of the two beta-blockers atenolol (selective beta 1 blocker) and pindolol (beta 1- and beta 2-blocker with Intrinsic sympathomimetic activity (ISA] in equipotential doses (100 mg atenolol vs. 15 mg pindolol). Male and female patients aged 20-65 years with essential hypertension WHO stages I and II were included. Patients were examined 1 and 6 months after the start of treatment, and side-effects were recorded. The antihypertensive effect was similar for the two drugs. After 1 month there was significantly less bradycardia (P less than 0.01), cold hands and feet (P less than 0.05) and tiredness (P less than 0.02) in the pindolol group, and less sleep disturbance (P less than 0.02) in the atenolol group. After 6 months there was no significant difference in sleep disturbance, but the differences in the other side-effects remained significant. PMID- 2205705 TI - Diabetes mellitus in north Sweden: prevalence assessed from prescriptions for anti-diabetic agents. AB - A prescription inventory was performed over a period of 3 months in all pharmacies in Sweden's northernmost province. Norrbotten, in order to assess the prevalence of diabetes treated with insulin and oral anti-diabetic agents. A total of 4869 prescriptions were collected from 3482 individuals, of whom 1746 (50.1%) were men. The prevalence of drug-treated diabetes was thus 13.27/1000 inhabitants (95% confidence interval (CI) 12.8-13.7) in the province. Nearly half (47.9%) of all drug-treated diabetics were treated with insulin and the majority (74%) were over 55 years of age, with only 449 (13%) being less than 40 years old. The prevalence of diabetes was highest in individuals aged 75-84 years; in this age group it was 55.47/1000 (95% CI 50.9-58.7). There was considerable regional variation in the prevalence of diabetes in Norrbotten, with a mean prevalence of 23.84/1000 (95% CI 22.1-25.6) in the municipalities in the Tornea Valley, compared to 13.08/1000 (95% CI 1.19-1.28) for the remainder of Norrbotten. While there was no difference in the prevalence of drug-treated diabetes between men and women in the province as a whole, a slightly higher prevalence was found in women (27.41 vs. 24.73/1000) in the Tornea Valley. The prevalence of diabetes mellitus in individuals over 40 years of age was 36.62/1000 (95% CI 3.73-4.36) in The Tornea Valley, 24.38/1000 (95% CI 22.8-24.7) in the remainder of Norrbotten, and 27.88/1000 (95% CI 2.50-2.68) in the province as a whole. The estimated prevalence of diabetes mellitus in Norrbotten, including patients treated by diet alone, was of the order of 20.21/1000, with a prevalence of 40.00/1000 in subjects over the age of 40 years. Thus the prevalence of diabetes appears to be higher in the Tornea Valley than in the rest of Norrbotten, while it is apparently lower than has been reported in North Finland. PMID- 2205706 TI - Charles F. Tate Jr., M.D. A brave pioneer in the fight against smoking. PMID- 2205707 TI - Stroke rehabilitation. Has it proven worthwhile? AB - Although rehabilitation services have been provided for stroke patients for several decades, no well-designed controlled studies have actually correlated statistically significant outcomes with a set of therapeutic guidelines. This paper reviews five recently published studies which attempted to evaluate the relative benefit of rehabilitation for victims of stroke. Relevant issues concerning study design are examined in the context of each report. Considering both the growing impact of this illness as well as the paucity of accurate information on the benefits of rehabilitative therapy, Congress should allocate funds to invoke a national stroke registry as a first step toward future analyses of stroke care needs. PMID- 2205708 TI - Complement mediated serum cytotoxicity against oligodendrocytes: a comparison with other cells of the oligodendrocyte-type 2 astrocyte lineage. AB - Rat oligodendrocytes are known to be susceptible to complement attack when exposed to homologous serum as a consequence of anti-myelin antibody independent classical pathway complement activation and attack. We have now compared this susceptibility with that of other cells of the oligodendrocyte-type 2 astrocyte (O-2A) lineage, and show that while type 2 astrocytes are not sensitive, O-2A progenitors are only relatively resistant to serum cytotoxicity, higher concentrations of complement resulting in cell damage. The implications of these findings for the pathogenesis of demyelinating disease are discussed. PMID- 2205709 TI - Immunoreactivity of antibodies raised against synthetic peptide fragments predicted from mid portions of dystrophin cDNA. AB - We synthesized 3 peptide fragments predicted by residues 2354-2368 (peptide I), 2310-2324 (peptide II) and 2255-2269 (peptide III) on the mid-portion of the human dystrophin cDNA map where the most frequent intragenic deletions occurred in Duchenne muscular dystrophy. Rabbit antibodies against these peptides were raised and cryosections of 47 biopsied muscles were studied immunohistochemically. The 47 biopsied muscles included the quadriceps femoris muscles of 8 Duchenne muscular dystrophy patients, 8 child and 5 adult normal controls, 1 facioscapulohumeral dystrophy, 2 limb girdle dystrophy, 3 myotonic dystrophy, 3 polymyositis, 1 mitochondrial myopathy, 1 nemaline myopathy, 3 amyotrophic lateral sclerosis and the extensor digitorum longus muscles of 6 mdx mice (C57BL/10ScSn-mdx) and 6 normal control mice (C57BL/10ScSn). The peptide I antiserum continuously stained the myofiber surface membranes in 8 child and 5 adult normal control muscles, and in 14 other muscles from various neuromuscular diseases, but failed to stain the surface membranes in normal control mice. The surface membranes of 8 Duchenne muscles were not stained by the peptide I antiserum except for a few myofibers. Although the ELISA titers of peptide I, II and III antibodies were high, immunostaining by peptide II antiserum showed no reaction in the myofibers of any of the biopsied muscles, and immunostaining by peptide III antiserum revealed faint reactions on the myofiber surface membranes of all biopsied muscles, including the mdx control mouse muscles except for the Duchenne and mdx myofibers. PMID- 2205710 TI - The MPTP model: versatile contributions to the treatment of idiopathic Parkinson's disease. AB - In human and subhuman primates, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces irreversible clinical, biochemical and neuropathological alterations highly reminiscent of those observed in Parkinson's disease. The MPTP model has provided the best available tool to date for the assessment of efficacy and side-effects of symptomatic treatments of Parkinson's disease. In addition, the mechanism of action of MPTP has offered a basis for the development of novel therapeutic strategies aimed at the prevention of Parkinson's disease. PMID- 2205711 TI - Association of intracranial meningiomas and aneurysms. Report of three cases and review of the literature. AB - The Authors report three personal cases of association between meningioma and arterial aneurysm, both intracranial. Twenty-three similar cases are referred in the literature, bringing the total to 26. Of these 26, the overall average age at diagnosis was 48.3 years: 17 were females and 9 males. The predominant site for the meningioma was the cerebral convexity and for the aneurysm the anterior communicating artery. Meningiomas were multiple in 5 cases and the aneurysms were multiple in the same number of cases. In 21 cases the meningioma was removed: in 11 of these the aneurysm was treated simultaneously. In the majority of cases the aneurysm was an accidental finding during neuroradiological investigation to document the meningioma; panangiography is reported to have been performed only in a few cases. Greater use of the latter would probably have revealed a higher incidence of this rare association. The greater frequency found of the association of aneurysm and multiple meningiomas makes it advisable to perform panangiography in all such cases. The best long-term results were obtained in the cases where the meningioma and aneurysm were operated simultaneously. PMID- 2205713 TI - Massive primary chylopericardium: a case report. AB - A large pericardial effusion was discovered in an asymptomatic 12-year-old boy admitted for an elective orthopedic procedure. On physical examination, heart rate was 96 and blood pressure was 130/70 without paradox. The neck veins were not distended, but heart tones were distant. Chest roentgenogram (CXR) showed an enlarged cardiac silhouette. Echocardiogram showed a massive pericardial effusion compressing the right atrium, with depressed ventricular contractility. Pericardiocentesis yielded 450 mL of chylous fluid. A percutaneous pericardial drain was placed and drained another 400 mL of chyle. Pericardial fluid reaccumulated even though the patient was on a low-fat diet, and 1 week after admission left thoracotomy was performed with partial pericardiectomy and pericardial window. There was 1 L of chyle in the pericardial sac; frozen section of the pericardium showed lymphangiectasia. Chest tube drainage diminished rapidly and the patient was discharged. Follow-up CXR at 1 week showed fluid in both pleural spaces requiring bilateral tube thoracostomies again draining chyle. Even with total parenteral nutrition (TPN), 500 mL/d of chyle drained from the pleural tubes. Right thoracotomy with ligation of the thoracic duct was performed after 1 week of TPN. Pleural drainage abruptly dropped, and there has been no reaccumulation in either the pleural spaces or pericardium at 6-month follow-up. This case dramatically supports early thoracic duct ligation and partial pericardiectomy as the treatment of choice for primary massive chylopericardium. PMID- 2205712 TI - The spectrum of appendiceal disease in cystic fibrosis. AB - A retrospective review of 1,220 cystic fibrosis (CF) patients between 1965 and 1989 identified 60 patients who underwent appendectomy. Ten had appendectomy prior to referral and 16 had an incidental appendectomy (primarily meconium ileus). Among the remaining 34 patients, acute appendicitis was present in 19 (1.8% incidence). "Classic appendicitis"--acute abdominal pain shifting to the right lower quadrant (RLQ), focal RLQ tenderness, and elevated white blood cell (WBC) count--was present in 15. Four additional inflamed appendixes were removed in patients following incorrect preoperative diagnosis. Thirteen of these 19 were perforated. Complications included wound infection (2), pelvic abscess (1), ileal obstruction requiring ileostomy (1), and pelvic hematoma (1). There were no deaths. One patient with acute RLQ pain and tenderness had a normal appendix. Seven patients (mean, 20 years) had chronic, intermittent, focal RLQ pain and tenderness not originating periumbilically with a normal WBC count and temperature. At exploration, these appendixes were enlarged and tensely distended with inspissated mucus. Microscopic examination showed no inflammation. Appendectomy resulted in resolution of symptoms without complications. Four additional patients with intermittent RLQ pain and tenderness and a history of recurrent intussusception presented with ileocolic intussusception. Persistent postreduction symptoms in three and failure of reduction in the fourth necessitated celiotomy at which time tensely distended appendixes were removed. Appendectomy led to resolution of symptoms. Three additional enlarged noninflammed appendixes were incidentally removed in asymptomatic patients undergoing unrelated intraabdominal procedures. Appendiceal disease in CF patients represents a spectrum ranging from simple mucous distention to acute appendicitis with perforation. CF patients with pain secondary to a noninflamed distended appendix represent a distinct syndrome cured by appendectomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2205714 TI - Carotid artery repair after pediatric extracorporeal membrane oxygenation. AB - Extracorporeal membrane oxygenation (ECMO), which has been shown to dramatically improve survival in selected neonatal patients, is now being used in some centers for pediatric patients with respiratory and cardiac failure. One of the major concerns with ECMO support is the permanent ligation of the right common carotid artery. We have used ECMO to support 10 pediatric patients with cardiac failure and 22 patients with respiratory failure. Thirty-one were cannulated via the common carotid artery and internal jugular vein on the right. Five of the last six patients with respiratory failure survived. One was on ECMO for 21 days, so the carotid artery was not amenable to repair. In the other four survivors the common carotid artery was reconstructed at the time of decannulation. In one patient, a segment of the artery was resected because of an intimal injury, and a primary anastomosis was performed. In all four, color Doppler studies of the artery prior to discharge were normal. None had clinical evidence of emboli, and a cranial computed tomography (CT) scan was normal in all four patients. These data suggest that in many pediatric patients supported with ECMO, reconstruction of the common carotid artery can be performed with low risk of embolic complications. Long-term follow-up is needed. PMID- 2205715 TI - Use of ultrasound and upper gastrointestinal (GI) x-rays to diagnose pyloric stenosis. PMID- 2205716 TI - [Artificial blood: the future of blood transfusion? II. Blood substitutes other than hemoglobin solutions]. AB - Part 2 discusses the state-of-the-art in oxygen-transporting blood substitutes other than hemoglobin solutions (Part 1); these are the fluorocarbon emulsions, the hemoglobin liposomes and other products such as oxygen-chelating agents. The substitutes reviewed here may play an important future role; before then, their stability, ease of administration, innocuity and value in human clinical medicine must be ensured. PMID- 2205717 TI - [The medicinal leech Hirudo medicinalis: clinical use of the animal and therapeutic prospects of hirudin]. AB - Blood sucking leech, Hirudo medicinalis, used in Medicine for very long, knew an intensive employment during early 18e century but its excess was responsible of the temporary disparition of the animal from the therapeutics. Leech has currently recovered a clinical use, especially in microsurgery. On the other hand, hirudin, main active compound isolated from leech extract and also known and used for long, offers interesting outlooks by its anticoagulant and antithrombic properties. This explains the great interest of hirudin preparation by molecular genetics. PMID- 2205718 TI - [PAF-acether antagonistic pyrrolo[1,2-c]thiazoles: from RP 48740 to RP 59227]. AB - The optimisation of the PAF antagonistic activity of RP 48740 led to the discovery of still more potent molecules of the pyrrolo[1,2-c]thiazole family: RP 52629, RP 52770 and RP 59227. The latter compound, for which a stereo-specific synthesis was developed, exhibits a very high potency as a PAF receptor antagonist. PMID- 2205719 TI - Wheelchair racing sports science: a review. AB - Wheelchair racing science and the performance of athletes involved in wheelchair racing have developed rapidly in recent years. With increasing interest in this sport, the need arises to identify areas where further research is necessary and cooperation between individuals with various backgrounds is encouraged. Many of the problems facing investigators in this field require knowledge in several areas of science and engineering, which suggests an interdisciplinary approach to these issues. Further progress would also benefit from the development of more quantitative methods for the classification of wheelchair athletes, or a restructuring of the classification system; development of sophisticated instrumentation for racing wheelchairs; standardization of test procedures and more complete reporting of results of studies; and, more in-depth mathematical modelling and computer simulation of wheelchair racing. This review presents an overview of four areas of wheelchair racing science: 1) classification of wheelchair athletes; 2) design and analysis of racing wheelchairs; 3) biomechanics of racing wheelchair propulsion; and, 4) training and coaching of wheelchair racers. PMID- 2205720 TI - [Skin AVA and its contribution to heat transfer through the skin]. PMID- 2205722 TI - Avoidance of used endometrial sites by blastocysts of the bank vole, Clethrionomys glareolus. AB - In bank voles blastocysts arising from mating immediately after parturition do not implant in used zones of the preceding pregnancy but in the regions between them. However, if mating is postponed until 12 or more days after parturition blastocysts do implant in used zones of the previous pregnancy. Implantations also occur at zones used two pregnancies previously. It seems likely that the absence of implantations at recently used zones of the uterus is determined by the uterus rather than blastocysts. PMID- 2205721 TI - Stimulation by hCG of ovarian inactive renin synthesis in rabbit preovulatory theca cells. AB - The origin of ovarian renin and its regulation by hCG were investigated in rabbit periovulatory follicles and cultured preovulatory follicular cells. Intracellular content of renin in thecal cells was 8-fold greater than of granulosa cells. In vivo, administration of hCG increased intracellular content of renin in thecal but not granulosa cells. Similar results were obtained for cultured follicular cells, from which renin was partly released into the medium. In vitro, hCG increased intracellular renin content of thecal but not granulosa cells, without obvious effect on release. Approximately 95% of ovarian renin was inactive, but could be activated by trypsin. Thecal renin was antagonized in vitro by renin antiserum, indicating a specific renin activity. Our study establishes in the rabbit the thecal cell origin of ovarian inactive renin and demonstrates hCG regulation of its synthesis. PMID- 2205723 TI - Breeding of captive bank voles (Clethrionomys glareolus) related to dynamics of source populations. AB - Proportionately fewer female bank voles from cyclic or dense populations bred than did females from sparse or non-cyclic populations when brought into a laboratory and kept as monogamous pairs for at least 1 year. Similarly, fewer litters were produced by females from cyclic or dense populations. Breeding frequency and litter production did not differ in the second laboratory generation. Large variance in litter numbers indicated further changes in reproduction in response to the laboratory environment. Certain differences between origins still persisted after long-term laboratory breeding. The regional variations between field-born animals are most parsimoniously explained by differences in sensitivity to density. PMID- 2205725 TI - Primary chemotherapy can avoid mastectomy, but there is more to it than that. PMID- 2205724 TI - Expression of substrate specificity in facilitated transport systems. AB - In facilitated transport systems the carrier reorientation step is shown to be largely independent of the forces of interaction between the substrate and the carrier site, whereas in coupled systems (obligatory exchange or cotransport) reorientation proceeds at the expense of the binding force developed in the transition state. In consequence, the expression of substrate specificity is expected to differ in the two systems. In the facilitated transport of analogs no larger than the normal substrate, the affinity but not the maximum rate of transport can vary widely; with larger analogs, both the affinity and rate can vary if steric constraints are more severe in the translocation step than in binding. In coupled transport, by contrast, the translocation step can be highly sensitive to the structure of the substrate, and binding much less sensitive. The theory agrees with published observations on facilitated systems for choline and glucose in erythrocytes, as well as on Na(+)-coupled systems for the same substrates in other cells. The following mechanism, which could account for the behavior, is proposed. In facilitated systems, the transport site fits the substrate closely and retains its shape as the carrier undergoes reorientation. In coupled systems, the site is initially looser, but during carrier reorientation it contracts around the substrate. In both systems, the carrier encloses the substrate during the translocation step, though for a different reason: in coupled but not in facilitated systems the binding force enormously increases in the enclosed state, through a chelation effect. In both systems, steric interference with enclosure retards the translocation of bulky substrate analogs. PMID- 2205726 TI - Cyclosporine: vital in today's transplantation, but questions remain about tomorrow. PMID- 2205727 TI - An interpretation of Michelangelo's Creation of Adam based on neuroanatomy. PMID- 2205728 TI - The phospholipid/arachidonic acid second messenger system: its possible role in physiology and pathophysiology of metabolism. AB - The phospholipid/arachidonic acid second messenger system is a signaling system by which systemic regulators (hormones) and local mediators (tissue factors) control certain aspects of tissue metabolism. In vivo and in vitro evidence indicates that these effectors activate phospholipolytic enzymes in cellular membranes. The products of these enzymatic reactions (such as inositol phosphates or arachidonic acid metabolites) can serve as second messengers that can potentially influence glucose, lipid and protein metabolism at the cellular level. Alterations in this second messenger system could be involved in metabolic changes associated with some pathologic conditions as well as certain drug treatments, and thus, a better understanding of the system could reveal new possibilities for therapeutic interventions. PMID- 2205729 TI - Glutamine: an anabolic effector? PMID- 2205730 TI - Glutamine metabolism and its physiologic importance. AB - The amino acid glutamine has important and unique metabolic functions. It is the most abundant free amino acid in the circulation and in intracellular pools and a precursor for the synthesis of amino acids, proteins, nucleotides, and many other biologically important molecules. It is the most important precursor for ammoniagenesis in the kidney, the major end product of ammonia-trapping pathways in the liver, a substrate for gluconeogenesis, and an oxidative fuel in rapidly proliferating cells and tissues. Glutamine also may have a number of important regulatory roles, increasing protein synthesis and decreasing protein degradation in skeletal muscle and stimulating glycogen synthesis in the liver. The demonstration that glutamine concentrations decrease and tissue glutamine metabolism increases markedly in many catabolic, stressful disease states has led to a reconsideration of the classification of glutamine as a nonessential amino acid and to the alternative hypothesis that glutamine may be a conditionally essential nutrient. This hypothesis has been supported by recent studies that have shown trophic effects of glutamine-supplemented diets on the growth of specific tissues and on total body nitrogen balance. These observations form the basis for current efforts to define the clinical usefulness of glutamine supplemented nutrition. PMID- 2205731 TI - Gut glutamine metabolism. AB - The gut plays a key role in interorgan glutamine metabolism in normal and catabolic states. During critical illness, the gut responds to prevailing metabolic pressures that may result in a temporary "reset" in interorgan glutamine flow. As the body recovers from the disease process, the alterations in gut glutamine metabolism revert to normal, which helps restore glutamine homeostasis. Overwhelming stresses, such as severe systemic infection, may lead to permanent organ dysfunction and further adaptive changes in glutamine metabolism. PMID- 2205732 TI - Liver glutamine metabolism. AB - A fundamental conceptional change in the field of hepatic glutamine metabolism is derived from an understanding of the unique regulatory properties of hepatic glutaminase, the occurrence of glutamine cycling, and the discovery of marked hepatocyte heterogeneities in nitrogen metabolism, with metabolic interactions between differently localized subacinar hepatocyte populations. This change provided new insight into the role of the liver in maintaining ammonia and bicarbonate homeostasis under physiologic and pathologic conditions. Glutamine synthetase is present only in a specialized cell population at the hepatic venous outflow of the liver acinus; these cells act as scavengers for ammonia and probably also for various signal molecules ("perivenous scavenger cell hypothesis"). The function of mitochondrial glutaminase is that of a pH- and hormone-modulated ammonia amplification system that controls carbamoylphosphate synthesis and urea cycle flux in periportal hepatocytes. Not only is hepatic glutamine metabolism essential for maintenance of bicarbonate and ammonia homeostasis, but glutamine itself can act in the liver as a signal modulating hepatic metabolism. This article summarizes some major aspects of hepatic glutamine metabolism, based on previous reviews. PMID- 2205733 TI - Properties of glutamine release from muscle and its importance for the immune system. PMID- 2205734 TI - Lung glutamine metabolism. AB - The role of the lungs in maintaining amino acid homeostasis has only recently been studied. The data suggest that the lungs play a key role in glutamine flow in both normal and catabolic states. Further studies are necessary to clarify the regulation of lung glutamine at the whole organ and cellular level. PMID- 2205735 TI - Interorgan glutamine metabolism during acidosis. PMID- 2205736 TI - Interorgan glutamine flow following surgery and infection. AB - Critical illness initiates some of the most profound alterations in interorgan glutamine metabolism observed in the laboratory as well as in clinical medicine. The interorgan flow becomes markedly altered and net glutamine utilization exceeds production, leading to glutamine depletion in several organs and a possible impairment of protein synthesis. As the patient recovers from the operation or sepsis, it appears that the flow of glutamine between tissues slowly reverts to "normal." During this process, food intake is resumed, the wound heals, activity generally returns to preillness levels, and, in most circumstances, the person is again well. PMID- 2205737 TI - [Detection of two Shiga-like toxins from Escherichia coli O157:H7 isolates by the polymerase chain reaction method]. AB - Fourteen isolates of E. coli O157:H7 and five isolates of S. dysenteriae type-1 were examined by polymerase chain reaction (PCR) for the structural genes (slt-I or slt-II), encoding Shiga-like toxins (SLTs). The two primer pairs (V1; 5'AGTTAATGTGGTGGCGAA and V2; 5'GACTGCGTCAGTGAGGTT for SLT-I, V3; 5'TTCGGTATCCTATTCCCG and V4; 5'TCTCTGGTCATTGTATTA for SLT-II) used were of the same positions representing the DNA sequence covering 471bp of the slt-I or slt II. A 5-microliter portion of boiled bacterial culture broth was used as template DNA in a PCR-reaction mixture of 50 microliters. Two classes, slt-I alone or both slt-I and slt-II, were recognized in E. coli strains. All of S. dysenteriae type 1 strains examined contained slt-I alone. Our results indicate that PCR using these primer pairs is a simple, rapid, sensitive, and specific method and suitable for use in routine diagnostic microbiology laboratories. PMID- 2205738 TI - [Clinical aspects of progressive muscular dystrophies]. PMID- 2205739 TI - [Molecular genetics of X-linked muscular dystrophy]. PMID- 2205740 TI - [Recent progress of bone marrow transplantation]. PMID- 2205741 TI - [Immunoserological area--with special reference to the current topics on antinuclear antibodies]. AB - In 1948, Hargraves described the phenomenon of the LE cells and equated it with systemic lupus erythematosus (SLE). Kunkel and his colleagues elucidated the immunochemical basis of this phenomenon, showing that it was related to the circulating autoantibodies to deoxyribonucleoprotein (DNP). Their pioneering studies led to the continuing discoveries of antinuclear antibodies (ANA) and today's considerable knowledge concerning the molecular identity of antigens and further consolidation of ANA. In addition to the role of diagnostic markers, spontaneously occurring autoantibodies, including anti-PCNA (proliferating cell nuclear antigen) antibody and anticentromere antibody (ACA), turned out to be useful as powerful probes for cell biology. In this study, the sera of patients with primary biliary cirrhosis (PBC) along with collagen diseases were examined for the presence of antinuclear antibodies. In using HEp-2 cells and chromosomes derived from K 562 as the substrates for the immunofluorescence method, the frequency of ANA and ACA in PBC sera were 84% and 44% respectively. Anti-DNA, antiSS-A and antiSS-B antibodies were found in one, 4 and one sera respectively. On the other hand, antibodies to nRNP, Sm and Scl-70 were not found in PBC sera. In some PBC patients with ACA, various complications related to collagen diseases were found to coexist. Our results indicated that there might be common serological abnormalities among patients with PBC, CREST syndrome and Sjogren's syndrome. PMID- 2205742 TI - [Serological evaluation of human T lymphotropic virus type-I infection in routine hospital samples, especially using serodia.HTLV-I]. AB - Particle agglutination (PA; Serodia-ATLA) and ELISA (Ei-test ATL) assays have been used as routine anti-HTLV-I antibody detection in Japan. However, inconsistent results were obtained by the above methods. We wished to develop criteria for serological confirmation of HTLV-I infection in Hospital samples. Sera obtained in our Hospital from October, 1988 to September, 1989 were tested by five methods of PA (Serodia-ATLA), new PA (improved on the PA; Serodia.HTLV I), ELISA-I (coated by HTLV-I infected cell lysates as antigens; Ei-test ATL), ELISA-II (coated by recombinant gag-env hybrid proteins as antigens) and IF. The HTLV-I seropositive rates using five methods were not different, ranged from 29.7 to 32.3% in 155 sera. However, PA assays appeared more false positive and rare false negative in some high titer sera. 13 sera as demonstrated negative for ELISA-I and positive for PA (ELISA-I(-)/PA(+] were reevaluated. As results, the antibody were confirmed in only 3 by new PA, 1 by ELISA-II and 2 cases by IF, respectively. On the other hand, 2 by new PA, 4 by ELISA-II and 2 by IF in 18 sera with ELISA-I(+)/PA(-) were interpreted as positive. Therefore, new PA is a remarkable improvement on the PA current model. PMID- 2205743 TI - [Studies on the role of leukocytes in the activation of intravascular coagulation in septicemia]. AB - To elucidate the role of leukocytes in intravascular clotting in patients with septicemia, plasma levels of thrombin-antithrombin III complex (TAT), soluble fibrin monomer complex (SFMC) and fibrinogen (Fbg) were determined in 33 patients with septicemia. Twenty out of 33 patients revealed a marked leukopenia (leukocyte count was less than 1,000/microliters) due to suppression of hematopoiesis by the administration of chemotherapeutic agents for the treatment of hematological malignancies. Thirteen out of 33 patients showed normal or increased leukocyte counts. Plasma levels of TAT and SFMC in septicemic patients with leukopenia were significantly lower than those in patients whose leukocyte counts were higher than 1,000/microliters. Plasma fibrinogen levels were significantly lower in patients whose leukocyte counts were higher than 1,000/microliters than those in patients with leukopenia. Plasma TAT levels were found to correlate well with the number of leukocytes in these patients with the correlation coefficient (R) of 0.67 (p less than 0.001). Significantly high positive correlation was observed between plasma TAT levels and the number of monocytes (R = 0.92, p less than 0.001). Significant correlation was also observed between plasma SFMC levels and the number of monocytes (R = 0.72, p less than 0.001). No significant correlation was found between the number of platelets and TAT levels. These findings suggest that leukocytes (especially monocytes) play a critical role in activating intravascular coagulation in septicemic patients. PMID- 2205744 TI - [Measurement of FDP-D-dimer in DIC and pre-DIC]. AB - We measured FDP-D-dimer value in disseminated intravascular coagulation (DIC), pre-DIC (within 7 days before onset of DIC) and suspected DIC (not completely satisfying the DIC criteria). The level of FDP in many patients with pre-DIC was normal, but the level of FDP-D-dimer in most patients with pre-DIC was increased. FDP was markedly increased one day before onset of DIC but FDP-D-dimer was increased 7 days before the onset. FDP was significantly higher in DIC than in pre-DIC, but it was not higher in pre-DIC than in suspected DIC. In patients with hematological malignancies, FDP-D-dimer was statistically higher in DIC than in pre-DIC and in pre-DIC than in suspected DIC, but in non-hematological malignancies, FDP-D-dimer was not significantly different among the 3 groups. The peak increase of FDP-D-dimer was noted at a DIC score of 7 or 8. The correlation of FDP-D-dimer with FDP was better in pre-DIC than in DIC, and the ratio of FDP-D dimer to FDP was higher in pre-DIC. FDP-D-dimer was not correlated with fibrinopeptide A or B beta 15-42 in pre-DIC. It is speculated that pre-DIC is a hypercoagulable state and FDP-D-dimer may be useful to the diagnosis of pre-DIC. PMID- 2205745 TI - [Morphological consideration of the bronchial arteries and its interventional angiography]. AB - The authors dissected the bronchial arteries macroscopically in 40 human adults. (1) Two right and two left bronchial arteries were most commonly observed in 19 cases (48%). (2) Besides the intercostobronchial artery, one more right bronchial artery was mainly distributed to the lower lobe of the right lung. (3) Relationship between the intrapulmonary distribution of each bronchial artery and the lobe of the lung was not definite. Technological considerations of the BAG were presented from the results of this study. PMID- 2205746 TI - [Urology and medical engineering]. PMID- 2205747 TI - [A case report of Cushing syndrome due to three distinct adenomas of the right adrenal]. AB - A case is presented of a 40 y.o. female with Cushing's syndrome. Her plasma glucocorticoid values were elevated (11-deoxy-cortisol: 3.46 ng/ml, cortisol: 25.6 micrograms/dl and cortisone: 35.7 ng/ml) with loss of diurnal variation. Urine 17-OHCS value failed to b suppressed by high dose dexamethasone and was unchanged after metyrapone administration. Her plasma mineral corticoids and androgens were within normal limits. There were 3 separate tumors in the right adrenal on CT and the left adrenal had no uptake on 131I-adosterol scintigram. We, therefore, diagnosed her illness as Cushing's syndrome due to unilateral multiple adenomas. Gross and histological examination of the right adrenal revealed one compact cell dominant adenoma and two clear cell dominant adenomas. This is the 4th case of Cushing syndrome due to unilateral multiple adrenal adenomas in Japan. PMID- 2205748 TI - [Mucin-producing cystadenoma (borderline malignancy) of the renal pelvis and ureter. A case report]. AB - The patient was a 63-year-old women who visited our hospital with the chief complaints of swelling, chills, fever and right lumbago. Fifteen years ago, she received surgical exploration for right renal stones at another department of urology. A large, soft and round kidney was palpable from the right upper quadrant of abdomen to the right lower abdomen. The parenchyma of the right kidney was thinned and inside the kidney there was a huge amount of yellowish mucin. The histological diagnosis was mucin-producing cyst-adenoma (borderline malignancy) of the renal pelvis and ureter. Mucin-producing cystadenoma of the renal pelvis and ureter origin was very rare, and only 4 similar cases to our patient were so far reported. PMID- 2205749 TI - Renal bone disease 1990: an unmet challenge for the nephrologist. PMID- 2205750 TI - Regulation of renal kallikrein synthesis and activation by glucocorticoids. AB - The effects of endogenous and exogenous glucocorticoids on renal active and prokallikrein levels (ng/mg protein) and in vivo kallikrein synthesis rate were studied in the conscious rat. Within two hours after low dose methylprednisolone (MP, 0.0125 to 0.05 mg/100 g body wt), active kallikrein and prokallikrein fell (29.1 +/- 2.3 and 35.1 +/- 2.7 ng/mg protein, respectively, compared to 38.4 +/- 3.7 and 42.7 +/- 3.4 in vehicle-treated rats, P less than 0.05 or less). These changes were accompanied by a significant fall in prokallikrein synthesis rate relative to total protein synthesis. The reductions in active and prokallikrein levels were transient, dissipating by six hours. With increasing MP doses, there was further dose-dependent reduction in active kallikrein. However, prokallikrein levels increased to normal as the MP dose was increased despite continued suppression of synthesis, suggesting that prokallikrein activation was inhibited. Renal kallikrein levels were also examined in relation to changes in endogenous glucocorticoid levels. In intact rats, three hours after plasma corticosterone peaked (10 p.m.), active and prokallikrein levels were 30.2 +/- 2.9 and 27.0 +/- 1.6 ng/mg protein, respectively, compared to 36.9 +/- 2.3 and 37.2 +/- 2.6 (P less than 0.005) three hours after the corticosterone nadir (11 a.m.). Furthermore, adrenalectomy increased active and prokallikrein (47.3 +/- 4.8 and 87.3 +/- 6.0 ng/mg protein, respectively), compared to levels in intact or shamoperated rats (intact: 32.9 +/- 2.9 and 54.9 +/- 5.3 ng/mg protein, P less than 0.01 or less). Adrenalectomy also eliminated the diurnal changes in kallikrein levels seen in intact rats. These data suggest that renal prokallikrein synthesis and activation are physiologically regulated by glucocorticoids. PMID- 2205753 TI - Percutaneous renal biopsy utilizing real time, ultrasonic guidance and a semiautomated biopsy device. PMID- 2205751 TI - Polymeric IgA and immune complex concentrations in IgA-related renal disease. AB - Polymeric IgA (PIgA) and immune complex concentrations in IgA-related renal disease were measured in cross sectional and longitudinal studies to establish the relationship between these parameters and both mucosal infection and renal dysfunction. These studies were performed in 50 patients with IgA nephropathy (IgAN), 17 patients with Henoch Schonlein purpura nephritis (HSPN), 11 control patients with IgA negative, diffuse mesangial proliferative glomerulonephritis (DMPGN) and 50 healthy controls. Total PIgA (PIgAT) and PIgA subclass concentrations were measured using a secretory component binding enzyme immunoassay and isotype specific immune complex concentrations were measured using conglutinin (K) binding immunoassays. In cross sectional studies patients with IgAN were found to have increased concentrations of PIgAT, PIgA1, K-IgA1 and K-IgA2 compared to controls. In the longitudinal studies controls and patients had significant increases in PIgAT and PIgA1 concentrations during infection. However, in patients with IgAN, the increases were greater, persisted for longer, and PIgA2 concentrations were also increased. K-IgA1 and K-IgA2 concentrations increased significantly during episodes of infection in IgAN patients in contrast to controls. Patients with HSPN had results similar to those of IgAN patients. No significant correlation was found between PIgA or K-IgA concentrations, and either serum creatinine concentrations or the degree of hematuria. The results indicate that patients with IgA-related renal disease have abnormal regulation of PIgA and immune complexed IgA, and that these abnormalities are exaggerated during mucosal infection. PMID- 2205752 TI - A blood protein monitor for the continuous measurement of blood volume changes during hemodialysis. PMID- 2205754 TI - Immunoadsorption in the sensitized transplant recipient. PMID- 2205756 TI - Laryngotracheal transection. PMID- 2205755 TI - Psychological risk factors and sports injuries. AB - Injuries sustained during competitive sport activities are accepted as an inherent part of the game. While it may be true that the associated risk of participating in certain sports increases the chance of becoming hurt, it is safe to assume many injuries can be avoided if preventive medicine is practiced. Conditioning and strength training go a long way in protecting the athlete from possible harm, but in some cases this is not enough. The accumulated effect of psychological stressors (in and outside the athletic world) may cloud the mental functioning of the athlete and override physical conditioning enough to precipitate injury or prolong it. After extensive reviews of literature, it has been determined that a collective researched list of psychological risk factors can be recognized which may predispose an athlete (especially in a contact sport) to injury (real or imagined). PMID- 2205757 TI - The AMA proposal to improve access to affordable, quality health care. PMID- 2205758 TI - Electrostatic potential maps at the quantum chemistry level of the active sites of the serine peptidases, alpha-chymotrypsin and subtilisin. AB - The electronic properties of the active-sites of the structurally unrelated serine peptidases, alpha-chymotrypsin and subtilisin, have been expressed in the form of three-dimensional electrostatic potential maps derived from integrals calculated at the quantum chemistry level. As a consequence of the asymmetrical distribution of the secondary structures that occur within a 7 A sphere around the serine of the catalytic triad, the active sites are highly polarized entities and exhibit large dipole moments. One part of the active sites generates a nucleophilic suction-pump. Its isocontour at -10 kcal mol-1 defines an impressive, negatively-charged volume which bears a narrow channel in the immediate vicinity of the active-site serine 195 in alpha-chymotrypsin or 221 in subtilisin. In native alpha-chymotrypsin, there is a perfect complementation between this nucleophilic suction-pump and the positively-charged electrophilic hole that is generated by the backbone NH of Ser 195 and Gly 193. In subtilisin, generation of the complementing electrophilic hole requires binding of a carbonyl donor ligand and may be achieved by rotation of the side-chain amide of Asn 155 towards the backbone NH of Ser 221. Small variations in the atomic co-ordinates of alpha-chymotrypsin used for the calculations, the presence of water molecules in its active site and the occurrence of point mutations in the amino acid sequence of subtilisin have little effects on the shape and characteristics of the electrostatic potential. PMID- 2205759 TI - Dr. William J. Mayo's European and Latin American goodwill efforts. PMID- 2205760 TI - Medical symbols: lamp of knowledge (life). PMID- 2205761 TI - Biplanar transesophageal echocardiography: anatomic correlations, image orientation, and clinical applications. AB - Clinical transesophageal echocardiography is a rapidly expanding diagnostic procedure. Conventional transesophageal endoscopes allow imaging from a single array mounted in the horizontal plane. This article introduces the clinical application of biplanar imaging, which incorporates a second orthogonal longitudinal plane. Our clinical experience with 291 patients who underwent biplanar transesophageal echocardiography is presented. The examination, technique, and resultant anatomic correlations unique to this new examination are discussed and illustrated. The anatomy is displayed in a familiar format comparable to the precordial examination. Biplanar imaging adds substantially to the comprehensive anatomic delineation of certain cardiac structures. PMID- 2205762 TI - Tension myalgia as a diagnosis at the Mayo Clinic and its relationship to fibrositis, fibromyalgia, and myofascial pain syndrome. AB - Tension myalgia is a diagnosis that has been in use at the Mayo Clinic for more than 40 years. The term describes a common muscle pain disorder that is conceptually similar to other muscle pain disorders such as fibrositis, fibromyalgia, and myofascial pain syndrome. This article outlines the history of these disorders and proposes "tension myalgia" as a term that unifies these separate diagnoses under one conceptual framework. Because the diagnostic criteria for tension myalgia have been vague, the Department of Physical Medicine and Rehabilitation at the Mayo Clinic has developed specific criteria for generalized, regional, and localized forms of this disorder. The recommended treatment approach includes reassurance, elimination of contributing factors, physical therapy to restore normal neuromuscular function, conditioning, and medications. PMID- 2205763 TI - Cardiopulmonary consequences of obstructive sleep apnea. AB - During sleep, oxygen consumption and systemic blood pressure decrease in normal subjects; during rapid eye movement sleep, irregular ventilation can be accompanied by brief periods of apnea. In patients with obstructive sleep apnea, alveolar ventilation during an apneic episode is immediately reduced to zero, and the metabolic demands for oxygen must be met from oxygen stores within the body. As the stores of oxygen within the lung are diminished, the rate of arterial oxyhemoglobin desaturation increases. The development of alveolar hypoventilation during wakefulness seems to be based on a balance between central ventilatory drives to breathe and mechanical loads placed on the respiratory system. Coexistent cardiopulmonary or neuromuscular disease in patients with obstructive sleep apnea contributes to the development of alveolar hypoventilation. During apneic episodes, the systemic blood pressure increases while the heart rate and cardiac output decrease. Both bradycardias and increased ventricular ectopic activity have been associated with these disordered breathing episodes. Because of the possibility of apnea-associated arrhythmias, patients with obstructive sleep apnea may be at increased risk for cardiovascular mortality. The influence of these recurrent nocturnal episodes of asphyxia on cardiovascular longevity needs further investigation. PMID- 2205764 TI - Uvulopalatopharyngoplasty for treatment of obstructive sleep apnea. AB - Currently, uvulopalatopharyngoplasty (UPPP) is the most common surgical procedure used for the treatment of obstructive sleep apnea. Patients with clinically significant obstructive sleep apnea in whom medical treatment has failed or who are unwilling to comply with medical therapy are considered candidates for UPPP. The initial surgical results obtained in nonselected patients with obstructive sleep apnea were highly variable, approximately half of the patients experiencing more than a 50% reduction in the frequency of disordered breathing events postoperatively. Although differences in surgical technique likely account for some of the variability, preoperative differences in the site (or sites) of upper airway collapse are also thought to influence the surgical results. Because UPPP involves resection of the uvula, distal margin of the soft palate, palatine tonsils, and any excessive lateral pharyngeal tissue, patients with anatomic narrowing and collapse confined to the velopharyngeal or retropalatal region of the upper airway are considered optimal surgical candidates. Fiberoptic pharyngoscopy, cephalometric roentgenography, computed tomography, and somnofluoroscopy are procedures that can be used preoperatively to help select optimal candidates for UPPP. The results suggest that the success rate of UPPP can approach 66% with careful preoperative selection of patients. PMID- 2205765 TI - Hospitalizations for patients with diabetes mellitus: changing perspectives. PMID- 2205766 TI - Nocardia asteroides pericarditis. PMID- 2205767 TI - Necessity of the assessment of health status in human immunogerontological studies: evaluation of the SENIEUR protocol. AB - Disease is frequent in ageing, and the many conflicting results in studies of the ageing process can be due to the presence of factors such as underlying disease or the use of medication. For immunogerontology, a solution to this problem was initiated in 1984 by a working party of EURAGE, the European Community's Concerted Action Programme on Ageing and Diseases. A protocol defining strict admission criteria to studies of ageing, the SENIEUR protocol, was elaborated. This protocol intends to limit the influence of disease and/or medication and to standardize admission criteria to immunogerontological studies. In subjects fulfilling the SENIEUR criteria, we found less immunological defects with ageing than generally stated. This could mean that many studies performed in not optimally healthy subjects describe defects that are not a consequence of the ageing process, but could be a result of underlying disease or of the influence of medication. For lymphocyte subsets, certain changes are only found in the comparison of SENIEUR groups of young and aged, while other changes are only found when non-healthy groups are compared. The occurrence of monoclonal gammopathies and autoantibodies was increased in ageing, but was also influenced by health status. Experience of other groups, and the objections against the protocol are discussed. PMID- 2205768 TI - Ethical issues in administrative continuous improvement. Applying the concept of prior notification to the conduct of firm trials. AB - Consensus exists concerning the distinctions to be drawn between clinical practice and research. When the latter is undertaken, established regulations require that protocols including plans for obtaining subjects' informed consent be submitted to Institutional Review Boards for approval. Less consensus or codification exists concerning evaluations conducted by managers in health care settings. The recent development of firm systems, in which randomized, controlled designs are employed to evaluate administrative interventions, provides a unique context in which to consider whether the subjects of administrative evaluations should be afforded protections granted subjects of clinical research. Accordingly, the history of firm trials from an ethical perspective is reviewed. At the University of Washington, participants of such studies are informed through the process of prior notification, an adaptation of procedures employed widely to inform patients that records or specimens may be used in epidemiologic or biomedical research. Prior notification appears to be a useful refinement of the firm system methodology, one that may have application to managerial manipulations in other arenas. PMID- 2205769 TI - Determinants of rural travel distance for obstetrics care. AB - This study examines the distances traveled for inpatient obstetrics care by women residing in rural Alabama in 1983 and 1988. During that time 23 rural hospitals in the state stopped providing obstetrics services and mean travel distances increased by 6.8 miles. However, in 1988 50% of rural pregnant women bypassed the nearest rural hospital still providing obstetrics services. Multivariate techniques are used to examine the effects of distance and service offerings of rural hospitals and their substitutes on the actual distance traveled for care. Patient characteristics are also considered. The most important finding is that a 5% increase in per capita income in the woman's home county is associated with a 20% increase in actual travel distance, other things equal. Implications for rural health policy are discussed. PMID- 2205771 TI - The angiotensin I converting enzyme inhibitors, captopril and Wy-44,655 attenuate the consequences of cerebral ischemia in renovascular hypertensive rats. AB - Global cerebral ischemia (four vessel model) was induced in renovascular hypertensive rats (two kidney, one clip model) chronically treated with intraperitoneal administration of angiotensin I converting enzyme inhibitors, either captopril (100 mg/kg per day) or Wy-44,655 (10 mg/kg per day). Mortality following cerebral ischemia was higher in renovascular hypertensive rats than in normotensive controls. Reduction of blood pressure with captopril or Wy-44,655, lowered mortality. In surviving renovascular hypertensive and normotensive rats cerebral ischemia induced hyperactivity and lesions of the CA1 area of the hippocampus. Prolonged treatment with captopril--but not with Wy-44,655--reduced hyperactivity and the extent of the CA1 lesions. In conclusion, hypertension increases mortality following cerebral ischemia but does not affect the extent of brain injury in survivors. Prior treatment with converting enzyme inhibitors lowers mortality. Treatment with captopril attenuates brain injury in survivors. PMID- 2205772 TI - Selectivity, objectivity and consensus in cellular pathology. PMID- 2205770 TI - Hypoaminoacidemia caused by imipramine but not by clenbuterol is dissociable from hyperglycemia and hyperinsulinemia. AB - The effects of the tricyclic antidepressant imipramine (20 mg/kg) and the beta adrenoceptor agonist clenbuterol (0.5 mg/kg) on the serum concentrations of tyrosine, tryptophan, glucose and insulin were compared 30 min after intraperitoneal injection. The drugs had nearly identical effects on serum tyrosine, which was reduced to 73% of control by both drugs, and on tryptophan, which was reduced to 72% by imipramine and to 66% by clenbuterol. In contrast, whereas clenbuterol raised serum glucose to 174% and insulin to 379% of control, imipramine had no significant effects on either glucose or insulin. The results clearly demonstrate that the effects of imipramine on blood amino acid levels are dissociable from effects on glucose and insulin. We conclude, therefore, that hypoaminoacidemia caused by imipramine is not mediated by stimulating insulin release. PMID- 2205773 TI - An investigation of culture media for the isolation of shigellae. AB - In this study we have investigated the efficiency of presently available culture media for the isolation of shigellae. XLD was found to be the medium of choice, combined with both less and more selective culture media (e.g. MacConkey, and Hektoen or DCA). By using these media in combination it was found that not only were shigellae isolated more often and efficiently, but fewer problems were encountered in isolating other Enterobacteriaceae. PMID- 2205774 TI - Production of high quality ground sections of bone containing metal implants to demonstrate osseo-integration: a simplified method. AB - A simple method is described for examining bone-titanium implant relationship using a modified embedding technique. The method involves complete dehydration with acetone prior to infiltrating and embedding in methyl methacrylate supplemented with dibutylphthalate. Slow polymerisation is initiated with benzoyl peroxide, allowed to progress at room temperature and completed at 56 degrees C. Using this method the apparent complete apposition of bone to the titanium fixture surface has been successfully demonstrated. PMID- 2205775 TI - Enhanced demonstration of cell surface immunoglobulins in paraffin-processed tissue. AB - A review of immunohistology, involving the more commonly encountered fixation protocols and the use of proteolytic agents, was undertaken in an attempt to establish a method whereby cell surface immunoglobulins could be reliably demonstrated in routinely processed paraffin tissue sections. Immunoglobulin D (IgD) was selected as a suitable antigen for detection in reactive lymphoid tissues, since it is known to be present both on the cell surface and in the cytoplasm. Using the indirect immunoperoxidase technique and the alkaline phosphatase/anti-alkaline phosphatase technique as standard methods, only cytoplasmic IgD was identifiable in paraffin sections with monoclonal antibodies. However, using polyclonal antisera a technique was established in which membrane bound IgD was also demonstrated in paraffin sections. PMID- 2205776 TI - Interleukin-2 (IL-2) immunotherapy. AB - Various forms of immunotherapy have been employed for the treatment of cancer patients during the past 5 years, with recombinant interleukin-2 (IL-2) having been widely used in these treatment regimes. The progress of IL-2 immunotherapy is discussed. PMID- 2205777 TI - Endorphins and exercise: physiological mechanisms and clinical implications. AB - In this paper we discuss recent experimental and clinical findings which lead us to propose that prolonged rhythmic exercise can activate central opioid systems by triggering increased discharge from mechanosensitive afferent nerve fibers (Group III or A-delta) arising from contracting skeletal muscle. We review evidence that supports the concept that many of the cardiovascular, analgesic, and behavioral effects of exercise are mediated by this mechanism and that the same or similar mechanisms are responsible for the central and peripheral effects of acupuncture. Based on this hypothesis, and supporting evidence from human and animal studies, we suggest a mechanism and a potential therapeutic role for exercise in the treatment of selected patients with disorders as diverse as hypertension, addiction, depression, and anorexia nervosa. PMID- 2205778 TI - Initial events in exercise-induced muscular injury. AB - Immediately following unaccustomed exercise, particularly that with eccentric contractions, there is evidence of injury to skeletal muscle fibers: a) disruption of the normal myofilament structures in some sarcomeres, observable with both light and electron microscope and b) loss of intramuscular proteins (e.g., creatine kinase enzymes) into the plasma, indicating damage to sarcolemma. This pathology is probably responsible for the temporary reductions in muscle force and delayed-onset soreness that can occur following eccentric exercise. The mechanisms underlying this injury are not known, although loss of intracellular Ca2+ homeostasis could play a primary role. In other experimental muscle injury models, elevated [Ca2+]i appears to cause release of muscle enzymes through activation of phospholipase A2, which in turn could induce injury to sarcolemma through production of leukotrienes and prostaglandins, through free O2 radical formation (in the subsequent lipoxygenase and cyclooxygenase reactions), and/or through release of detergent lysophospholipids. On the other hand, the mechanism responsible for the rapid damage to myofibrils caused by increased [Ca2+]i is unknown. Regardless of the cause(s), the initial and early events in the injury process are autogenetic; i.e., they are indigenous to the muscle cells and occur before phagocytic cells enter the injury site. PMID- 2205779 TI - Muscle strain injuries: clinical and basic aspects. AB - Indirect or strain injury to muscle is a common cause of athletic disability. Strain injuries often occur during powerful muscle eccentric contractions. Clinical studies suggest that most injuries cause partial disruption of certain characteristic muscles. Diagnostic imaging studies can demonstrate the location of many injuries. Laboratory studies show that partial and complete injuries exhibit disruption of muscle fibers near the muscle-tendon junction. Healing of partial injuries is characterized by an initial inflammatory response followed by a healing phase marked by fibrosis. Biomechanical studies show that muscle failure occurs at forces much larger than maximal isometric force, and stretch is necessary to create injury. Compared to the passively stretched muscle, muscle activated by nerve contraction and stretched to failure attains a small increase in force at failure, no change in strain to failure, and a large increase in energy absorbed prior to failure. These studies emphasize the ability of muscles to function as energy absorbers in preventing injury to themselves and to bones and joints. Experimental muscle stretching protocols show significant stress relaxation and reduction of stiffness in muscle due to inherent viscoelastic properties of muscle rather than to reflex-mediated effects. These viscoelastic properties may be useful in understanding how muscle injury might be prevented. PMID- 2205780 TI - Mechanisms of peripheral fatigue. AB - Fatigue can be defined as the failure to maintain an expected power output. This is often an antecedent to some sports-related injury. It is important for those involved in physical performance to be familiar with the variety of mechanisms which can lead to fatigue. All too often, a single factor is described as the cause of fatigue when actually fatigue may be a combination of factors that contribute to the sequence of events that results in decreased performance. It may be suggested that every step in the chain of events that leads to voluntary contraction of skeletal muscle could be a culprit in fatigue. Peripheral sites and processes include the motor neuron, neuromuscular junction, sarcolemmal membrane, excitation-contraction coupling, accumulation of metabolites, or depletion of fuels. Physical training is frequently designed to delay the onset of fatigue. The actual mechanism(s) add to the specificity concept, that is, a "specificity of fatigue". To the performer, the end result is the same, the inability to maintain his or her expected level of performance or power output. PMID- 2205781 TI - Muscle conditioning and muscle injuries. AB - Empirical and objective data suggest that muscle and connective tissue can undergo adaptations to physical training resulting in greater tissue mass and increased maximum tensile strength. These adaptations are especially apparent as a result of load bearing and resistive training. Furthermore, information is presented suggesting that pre-conditioning and in-season muscle conditioning, especially strength training, reduce injuries among athletes. Additionally, a theoretical model of training, "periodization", is offered as a method of increasing performance to maximum or optimal values while reducing overtraining and injury potential. Periodization of training can reduce overtraining potential and injury potential while optimizing performance by variation of volume, intensity, and exercise selection during a training program. PMID- 2205782 TI - Neurosarcoidosis: signs, course and treatment in 35 confirmed cases. AB - Thirty-five cases of biopsy-proven sarcoidosis with neurologic manifestations are reported. Neurosarcoidosis was the presenting symptom in 31% of cases and the only clinical manifestation in 17%. Mean follow-up time was 48 months. Central nervous system involvement was observed in 37% and meningitis in 40% of patients. Other manifestations were cranial nerve palsies (37%), peripheral neuropathy (40%), and myopathy (26%). Multiple neurologic manifestations were present in 51% of cases. All but 4 were treated with corticosteroids. Another immunosuppressive agent or cerebral irradiation was added in 6 and 2 patients, respectively. Complete recovery was observed in 46%, improvement in 46%, 4% remained stable, and 4% worsened. There were no deaths. We advocate treating neurosarcoidosis with corticosteroids as early as possible. If the patient's condition worsens, additional immunosuppressive agents or cerebral irradiation is warranted. PMID- 2205783 TI - Nontraumatic parenchymal brain hemorrhages. AB - Before the availability of computerized tomography (CT), it was estimated that 25% of parenchymal brain hemorrhages (PBH) was diagnosed as ischemic stroke. Clinical studies were biased toward large hemorrhages with high mortality rates. More recently, the full clinical spectrum of PBH has been appreciated only with studies correlating clinical findings and CT results. In the pre-CT era, hypertension was thought to be the major risk factor for PBH. Chronic hypertensive vascular changes were believed to cause arteriolar wall damage, and rupture of weakened dilated vessels thought to result in PBH. The occurrence of PBH in previously normotensive patients was underrepresented in pre-CT era studies. Current CT findings in PBH patients have shown that normotensive patients and hypertensive patients with chronic vascular changes have smaller hemorrhages resulting in lower mortality than hypertensive patients without chronic vascular changes. Because chronic hypertensive vascular changes are believed to be common in patients with PBH, this finding is unexpected and previously unreported. Chronic vascular changes may therefore offer some unexplained "protection" for brain blood vessels. Alternatively the mechanism of hypertensive PBH may be somewhat different than previously postulated. PMID- 2205785 TI - Antiketogenesis: its mechanism and significance. 1932. PMID- 2205784 TI - New and emerging etiologies for community-acquired pneumonia with implications for therapy. A prospective multicenter study of 359 cases. AB - Three hundred fifty-nine consecutive patients with community-acquired pneumonia admitted to university, community, and VA hospitals underwent a standardized evaluation, including specialized tests for Legionella spp. and Chlamydia pneumoniae (TWAR). The most common underlying illnesses were immunosuppression (36.3%), chronic obstructive pulmonary disease (32.4%), and malignancy (28.4%). The most frequent etiologic agents were Streptococcus pneumoniae (15.3%) and Hemophilus influenzae (10.9%). Surprisingly, Legionella spp. and C. pneumoniae were the third and fourth most frequent etiologies at 6.7% and 6.1%, respectively. Aerobic gram-negative pneumonias were relatively uncommon causes of pneumonia despite the fact that empiric broad-spectrum combination antibiotic therapy is so often directed at this subgroup. In 32.9%, the etiology was undetermined. Antibiotic administration before admission was significantly associated with undetermined etiology (p = 0.0003). There were no distinctive clinical features found to be diagnostic for any etiologic agent, although high fever occurred more frequently in Legionnaires' disease. Clinical manifestations for C. pneumoniae were generally mild, although 38% of patients had mental status changes. Mortality was highest for Staphylococcus aureus (50%) and lowest for C. pneumoniae (4.5%) and Mycoplasma pneumoniae (0%). We document that specialized laboratory testing for C. pneumoniae and Legionella spp. should be more widely used rather than reserved for cases not responding to standard therapy. Furthermore, realization that C. pneumoniae and Legionella spp. are common etiologies for community-acquired pneumonia should affect empiric antibiotic prescription. PMID- 2205786 TI - Treatment of endocrine and nonendocrine secretory diarrheal states with Sandostatin. AB - Endocrine tumors of the gastroenteropancreatic (GEP) axis elaborate excessive amounts of peptides that are potent intestinal secretagogues. The actions of these peptides on intestinal transport of water and electrolytes lead to the accumulation of fluid in the intestinal lumen and diarrhea. One of the most clinically relevant secretagogues is vasoactive intestinal polypeptide (VIP). Other relevant secretagogues elaborated from tumors are serotonin, prostaglandins, and kinins. Sandostatin (octreotide, Sandoz, Basle, Switzerland), a long-acting octapeptide analog of somatostatin, inhibits experimentally induced intestinal secretion and has been used successfully to treat patients with secretory diarrhea refractory to other pharmacotherapy. The effective dose is in the range of 50 to 200 micrograms, given subcutaneously two or three times daily. The mechanism for the inhibitory effect on secretion is not clearly understood but it appears to involve inhibition of the adenylate cyclase-cyclic adenosine monophosphate system as well as interference with calcium as an intercellular mediator of enterocyte secretion. A particularly interesting use of this drug has been to treat the watery diarrhea seen in patients with acquired immunodeficiency syndrome. It is also effective in other types of secretory diarrhea not associated with endocrine tumors. These include diabetic diarrhea, idiopathic secretory diarrhea of infancy, and high output ileostomy diarrhea. PMID- 2205787 TI - Future medical prospects for Sandostatin. AB - Because of its widespread distribution within the nervous system and gastroenteropancreatic (GEP) system, and its diverse physiological inhibitory actions on various gastrointestinal functions, including endocrine and exocrine secretion, motility, liver and splanchnic blood flow and absorption, native somatostatin has been viewed as a possible therapy for many diseases. However, its short duration of action and consequent limited clinical usefulness have been overcome with the availability of Sandostatin (octreotide, Sandoz Ltd), a long acting, synthetic octapeptide analog of the naturally occurring hormone. Sandostatin represents a significant advance in the treatment of growth hormone (GH) and thyrotropin (TSH)-secreting pituitary tumors and GEP endocrine tumors (carcinoid tumor, VIPoma, glucagonoma, insulinoma, and gastrinoma). Preclinical in vitro and animal studies have shown the antineoplastic activity of the compound. Moreover, because of a possible direct effect on somatostatin receptor positive endocrine tumor cells and an indirect effect whereby Sandostatin lowers GH, insulin-like growth factor type 1 (IGF-1), and numerous gastrointestinal peptides, Sandostatin may prove useful as an adjunctive therapy in cancer patients. In vivo labeling of somatostatin receptor-positive tumors with radiolabeled somatostatin analogs now allows localization of such tumors and their metastases. In addition, targeted irradiation of these tumors by beta particle-emitting isotopes attached to such somatostatin analogs may become possible. The use of Sandostatin in acute esophageal variceal bleeding, pancreatic pseudocysts, gastrointestinal, and pancreatic external fistulae, short bowel syndrome, dumping syndrome and acquired immunodeficiency syndrome (AIDS) related refractory hypersecretory diarrhea has provided encouraging results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2205788 TI - Pegademase. PMID- 2205789 TI - [The role of pulsed gel electrophoresis in the study of biological macromolecules]. AB - We present modern conceptions concerning movement of biopolymer molecules in a gel under the action of static and pulsed electric fields, and we basically analyse some mostly used techniques of pulsed electrophoresis and the results yielded by using them. Pulsed procedures are shown to essentially widen the possibilities of analytical electrophoresis and electrophoretic transblotting are elaborated. Cameras and buffer systems used are the same as in classical methods involving the constant electric field. Promising results were collected while using sine-mode voltage in the constant and pulsed variants of electrophoresis. It is stated that the exceptionally wide application of pulsed methods in laboratory practice requires development of adequate theoretical conceptions concerning the movement of linear and globular polymers in gel under alternating field. In this connection the investigation of potentials of pulsed electrophoresis with inversions of field direction as the most simple and universal process of DNA division in a wide range of molecular masses and the use in electrophoretic techniques of sine-mode voltage obtained directly from the industrial circuit are most significant. PMID- 2205790 TI - [Cloning and expression of the gene for thermostable pullulanase from Clostridium thermohydrosulfuricum in Escherichia coli]. AB - Using a pUC19-based genomic library of the anaerobic thermophilic bacterium C. thermohydrosulfuricum a DNA fragment that confers pullulanase activity to E. coli cells has been identified. Subcloning and restriction mapping procedures was carried out and the primary structure of the 5'-region of the pullulanase gene (pul) was determined. The pul enzyme was shown to be a protein with molecular weight of approximately 60,000. It was found that both pullulanase and glucoamylase activities resides in pullulanase. The intracellular distribution of pullulanase was studied. An E. coli strain that produces large amounts of thermostable pullulanase has been constructed. PMID- 2205791 TI - [Isolation and characteristics of thermostable pullulanase from Clostridium thermohydrosulfuricum produced by Escherichia coli cells]. AB - The expressed gene (pul) for a thermostable pullulanase from Clostridium thermohydrosulfuricum was cloned into Escherichia coli. The enzyme was purified from cell extracts of E. coli by thermoinactivation, ammonium sulphate precipitation and gel exclusion. The purified enzyme was characterized as monomer with both pullulanase and glucoamylase activities. The general physico-chemical and catalytic properties of this enzyme were obtained. In particular, pullulanase and glucoamylase activities were stable and optimally active at 65 degrees C. The pH optimum for activity was 5.8. The amino acid composition and amino acid sequence of N-terminal end were estimated. PMID- 2205793 TI - [Role of Doppler velocimetry in diagnosis of TMJ dysfunction. 1. Experimentation on Macaca fascicularis]. AB - The aim of this work has been to demonstrate that the tracing obtained by Doppler examination is the graphic representation of the movement and the speedy of the condyle and the disk. In order to achieve this result we have proved Doppler examination first of all on entire TMJ of a Macaca Fascicularis monkey and than on the same joint without the disk. PMID- 2205792 TI - [Express method of isolation of mammalian phenylalanine-tRNA-synthetase and preparation of monoclonal antibodies against this enzyme]. AB - A rapid and efficient procedure for isolating homogeneous beef liver phenylalanyl tRNA synthetase (EC.6.1.1) was developed that enables to purify the enzyme 5000 fold and to achieve the activity of 8 e.a.u. per mg of protein. The molecular mass of the native enzyme was estimated to be 260 kDa, for alpha subunit - 59 kDa, and for beta - 72 kDa. Two cellular clones were derived by means of hybridization of immunised splenocytes with myeloma cells. They secrete monoclonal antibodies, designated P6 and P1 2, that bind to human placental and bovine liver phenylalanyl-tRNA synthetases but not to the same enzymes from E. coli and T. thermophilus. P6 and P1 2 antibodies do not affect the aminoacylation capacity of human or bovine phenylalanyl-tRNA synthetases. By immunoblotting, it was shown that P6 antibodies recognize the alpha subunit of the enzyme. PMID- 2205794 TI - [Role of Doppler velocimetry in diagnosis of TMJ dysfunction. 2. Clinical evaluation]. AB - In order to evaluate the efficacy of Doppler effect in the diagnosis of dysfunctional TMJ sounds, we have analysed ten Doppler tracings of normal subjects, ten of subjects with reciprocal clicking and ten with locking (complete anterior dislocation of the disc). The results show that to every dysfunctional pathology corresponds a precise type of tracing whose acknowledgment is immediate. PMID- 2205795 TI - [Role of lower third molars in the development of dental malocclusion: review of the literature]. AB - The Author's aims was to review the role of the lower third molars in delayed crowding of the jaw. A global agreement exists on the fact that lower molars should be considered only one between several factors able to cause malocclusion. Finally, the germectomy of the third molars has to be performed only in carefully selected patients after a comprehensive diagnostic evaluation of the single case. PMID- 2205796 TI - [Neonatal orthopedic treatment of patients with congenital cleft lip and palate. 1. Development of treatment]. AB - The Authors go over the different stages that made up the development of the neonatal orthopedic treatment by dwelling upon the most interesting and important aspects of each technique. PMID- 2205797 TI - [Neonatal orthopedic treatment of patients with congenital cleft lip and palate. 2. Clinical considerations and evaluation of results]. AB - The Authors, after dealing with the evolution of this kind of therapy, illustrate the multidisciplinary protocol for the treatment of patients with cleft lip and palate and in particular they explain the technique used for the neonatal orthopedic treatment by analyzing its methods and purposes. PMID- 2205799 TI - Effect of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia. Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH) AB - BACKGROUND AND METHODS: The Program on the Surgical Control of the Hyperlipidemias (POSCH), a randomized clinical trial, was designed to test whether cholesterol lowering induced by the partial ileal bypass operation would favorably affect overall mortality or mortality due to coronary heart disease. The study population consisted of 838 patients (417 in the control group and 421 in the surgery group), both men (90.7 percent) and women, with an average age of 51 years, who had survived a first myocardial infarction. The mean follow-up period was 9.7 years. RESULTS: When compared with the control group at five years, the surgery group had a total plasma cholesterol level 23.3 percent lower (4.71 +/- 0.91 vs. 6.14 +/- 0.89 mmol per liter [mean +/- SD]; P less than 0.0001), a low-density lipoprotein cholesterol level 37.7 percent lower (2.68 +/- 0.78 vs. 4.30 +/- 0.89 mmol per liter; P less than 0.0001), and a high-density lipoprotein cholesterol level 4.3 percent higher (1.08 +/- 0.26 vs. 1.04 +/- 0.25 mmol per liter; P = 0.02). Overall mortality and mortality due to coronary heart disease were reduced, but not significantly so (deaths overall [control vs. surgery], 62 vs. 49, P = 0.164; deaths due to coronary disease, 44 vs. 32, P = 0.113). The overall mortality in the surgery subgroup with an ejection fraction greater than or equal to 50 percent was 36 percent lower (control vs. surgery, 39 vs. 24; P = 0.021). The value for two end points combined--death due to coronary heart disease and confirmed nonfatal myocardial infarction--was 35 percent lower in the surgery group (125 vs. 82 events; P less than 0.001). During follow-up, 137 control-group and 52 surgery-group patients underwent coronary-artery bypass grafting (P less than 0.0001). A comparison of base-line coronary arteriograms with those obtained at 3, 5, 7, and 10 years consistently showed less disease progression in the surgery group (P less than 0.001). The most common side effect of partial ileal bypass was diarrhea; others included occasional kidney stones, gallstones, and intestinal obstruction. CONCLUSIONS: Partial ileal bypass produces sustained improvement in the blood lipid patterns of patients who have had a myocardial infarction and reduces their subsequent morbidity due to coronary heart disease. The role of this procedure in the management of hypercholesterolemia remains to be determined. These results provide strong evidence supporting the beneficial effects of lipid modification in the reduction of atherosclerosis progression. PMID- 2205800 TI - Ophthalmology. PMID- 2205798 TI - Reduced mortality among children in southern India receiving a small weekly dose of vitamin A. AB - BACKGROUND: Clinical vitamin A deficiency affects millions of children worldwide, and subclinical deficiency is even more common. Supplemental vitamin A has been reported to reduce mortality among these children, but the results have been questioned. METHODS: We conducted a randomized, controlled, masked clinical trial for one year in southern India involving 15,419 preschool-age children who received either 8.7 mumol (8333 IU) of vitamin A and 46 mumol (20 mg) of vitamin E (the treated group) or vitamin E alone (the control group). Vitamin supplements were delivered weekly by community health volunteers who also recorded mortality and morbidity. Weekly contact was made with at least 88 percent of the children in both study groups. The base-line characteristics of the children were similar and documented a high prevalence of vitamin A deficiency and undernutrition. RESULTS: One hundred twenty-five deaths occurred, of which 117 were not accidental. The risk of death in the group treated with vitamin A was less than half that in the control group (relative risk, 0.46; 95 percent confidence interval, 0.30 to 0.71). The risk was most reduced among children under 3 years of age (6 to 11 months--relative risk, 0.28; 95 percent confidence interval, 0.09 to 0.85; 12 to 35 months--relative risk, 0.46; 95 percent confidence interval, 0.26 to 0.81) and among those who were chronically undernourished, as manifested by stunting (relative risk, 0.11; 95 percent confidence interval, 0.03 to 0.36). The symptom-specific risk of mortality was significantly associated with diarrhea, convulsions, and other infection-related symptoms. CONCLUSIONS: The regular provision of a supplement of vitamin A to children, at a level potentially obtainable from foods, in an area where vitamin A deficiency and under-nutrition are documented public health problems contributed substantially to children's survival; mortality was reduced on average by 54 percent. PMID- 2205801 TI - An outbreak of surgical-wound infections due to group A streptococcus carried on the scalp. PMID- 2205802 TI - Electrosurgery--Part I. The history of diathermy. PMID- 2205803 TI - A second class of synthetase structure revealed by X-ray analysis of Escherichia coli seryl-tRNA synthetase at 2.5 A. AB - The three-dimensional crystal structure of seryl-transfer RNA synthetase from Escherichia coli, refined at 2.5 A resolution, is described. It has an N-terminal domain that forms an antiparallel alpha helical coiled-coil, stretching 60 A out into the solvent and stabilized by interhelical hydrophobic interactions and an active-site alpha-beta domain based around a seven-stranded antiparallel beta sheet. Unlike the three other known synthetase structures, the enzyme contains no classical nucleotide-binding fold, and is the first representative of a second class of aminoacyl-tRNA synthetase structures. PMID- 2205804 TI - Frequent activation of N-myc genes by hepadnavirus insertion in woodchuck liver tumours. AB - The recent finding of c-myc activation by insertion of woodchuck hepatitis virus DNA in two independent hepatocellular carcinoma has given support to the hypothesis that integration of hepatitis B viruses into the host genome, observed in most human and woodchuck liver tumours, might contribute to oncogenesis. We report here high frequency of woodchuck hepatitis virus DNA integrations in two newly identified N-myc genes: N-myc1, the homologue of known mammalian N-myc genes, and N-myc2, an intronless 'complementary DNA gene' or 'retroposon' that has retained extensive coding and transforming homology with N-myc. N-myc2 is totally silent in normal liver, but is overexpressed without genetic rearrangements in most liver tumours. Moreover, viral integrations occur within either N-myc1 or N-myc2 in about 20% of the tumours, giving rise to chimaeric messenger RNAs in which the 3' untranslated region of N-myc was replaced by woodchuck hepatitis virus sequences encompassing the viral enhancer. Insertion sites were clustered in a short sequence of the third exon that coincides with a retroviral integration hotspot within the murine N-myc gene, recently described in T-cell lymphomas induced by murine leukaemia virus. Thus, comparable mechanisms, leading to deregulated expression of N-myc genes, may operate in the development of tumours induced either by hepatitis virus or by nonacute retroviruses in rodents. Activation of myc genes by insertion of hepadnavirus DNA now emerges as a common event in the genesis of woodchuck hepatocellular carcinoma. PMID- 2205806 TI - [Bionics: limits and perspectives]. AB - Bionics, based on analogies between living beings and technical systems, neglect fundamental differences, e.g., on the one hand, technology uses high temperatures, a mean closed to all living beings and, on the other hand, the cells of all organisms keep high autonomy. The first fact makes it possible, e.g., to construct airplanes three or four powers of ten heavier than the heaviest birds, whereas the second fact enables each cell to reproduce itself, to restore lost limbs or even the whole organism, far beyond the reach of technology. The symbiosis of organisms and technical installations (biotechnology) or, on a higher level, of mankind and environment, may be a guiding star for future development. PMID- 2205805 TI - Studying single living cells and chromosomes by confocal Raman microspectroscopy. AB - Many indirect methods have been developed to study the constitution and conformation of macromolecules inside the living cell. Direct analysis by Raman spectroscopy is an ideal complement to techniques using directly labelled fluorescent probes or of indirect labelling with mono- and polyclonal antibodies. The high information content of Raman spectra can characterize biological macromolecules both in solution and in crystals. The positions, intensities and linewidths of the Raman lines (corresponding to vibrational energy levels) in spectra of DNA-protein complexes yield information about the composition, secondary structure and interactions of these molecules, including the chemical microenvironment of molecular subgroups. The main drawback of the method is the low Raman scattering cross-section of biological macromolecules, which until now has prohibited studies at the level of the single cell with the exception of (salmon) sperm heads, in which the DNA is condensed to an exceptionally high degree. Ultraviolet-resonance Raman spectroscopy has been used to obtain single cell spectra (and F. Sureau and P. Y. Turpin, personal communication), but in this method absorption of laser light may impair the integrity of the sample. We have avoided this problem in developing a novel, highly sensitive confocal Raman microspectrometer for nonresonant Raman spectroscopy. Our instrument makes it possible to study single cells and chromosomes with a high spatial resolution (approximately less than 1 micron 3). PMID- 2205807 TI - [Molecular cell biology of the heat stress response. Part I]. AB - In a physiological range of hyperthermia all living systems respond with a complex reprogramming of cellular activities to provide a basis for survival during the stress period and for a rapid restoration of normal activities in the recovery period. A prominent characteristic of the response is the induced synthesis of heat-stress proteins which is likewise evoked by numerous chemical stressors. The common signal transduction chain leading to the activation of heat stress genes evidently involves the transient accumulation of abnormal proteins. The dominant HSPs belong to five conserved stress protein families, whose members are essential components of all living cells with general functions by far exceeding the stress response. PMID- 2205809 TI - EPO--one year later: a look at rehabilitation. The impact of long-term epoetin beta therapy on ESRD patient quality of life. AB - Long-term observational studies such as the one reported here represent the best chance for measuring the effects of epoetin treatment on quality of life as compared with conventional treatment. When scores were adjusted for between-group differences, patients receiving epoetin beta for an average of 18 months demonstrated significantly better quality of life in 16 of the 26 parameters reported. These measures included all global measurements, psychological well being as measured by IGA, sleep, rest, energy, SIP psychosocial subscale, and total SIP score. While differences were not significant, remaining measurements were higher in the epoetin beta group. On the basis of this study, epoetin beta treatment has a beneficial effect on energy, the ability to work, and participation in activities such as home management, recreation, and pastimes. While the mean score for ability to work was significantly higher in the epoetin beta-treated patients, the work category of the SIP was not significantly different from the untreated population. The fact that the latter scale was completed by only the small proportion of the patients who were actually working may have contributed to this insignificant finding. The current study demonstrates sustained benefit form epoetin beta compared with conventional therapy, even after 18 months. These long-term results validate previously published results of benefits seen during shorter-term epoetin therapy. PMID- 2205808 TI - Drosophila glue protein gene expression. A proposal for its ecdysone-dependent developmental control. AB - The primary targets of steroid hormones are genes. For the ecdysone-controlled genes of Drosophila larval glue proteins proximal and distal control elements were identified by mutagenesis and sequence comparison. Their presence is required for the correct stage- and tissue-specific expression of these genes. The supposed function of these elements is described in a working model. PMID- 2205810 TI - Medicare's budget on the Congressional-Administration bargaining table. PMID- 2205811 TI - Phenolized formalin fixation may obscure early histological changes of Creutzfeldt-Jakob disease. PMID- 2205812 TI - A history of infectious waste legislation and regulation and their impact on hospitals in New York City. PMID- 2205813 TI - A history of the Ray Brook State Tuberculosis Hospital. PMID- 2205814 TI - Initial in vivo tear protein deposition on individual hydrogel contact lenses. AB - We investigated and compared the initial composition, morphology, and time course of deposits on individual soft contact lenses of different water contents and surface charges in order to evaluate the potential for antigenic reactions and to predict the optimal frequency of lens replacement. Newly manufactured lenses were worn for graduated periods of time from 1 min to 8 h by subjects who were first adapted to daily wear soft lenses. The morphology and composition of the deposits were analyzed by histological staining, light microscopy, scanning electron microscopy (SEM), sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) with silver nitrate staining, and immunofluorescence microscopy. The protein bands of the acrylamide gels were divided according to their molecular weights into six groups which have been defined in the literature from tear analyses by electrophoretic techniques and include lysozyme, proteins migrating faster than albumin (PMFA), protein G, albumin, lactoferrin, and other proteins heavier than albumin such as Ig-G and secretory Ig-A. Specific proteins (lysozyme, PMFA, and protein G) were detected on individual lenses after as little as 1 min of wear. There was an increasing amount of protein deposited as the wearing time increased. Differences in the rates and amounts of deposition were more dependent on lens water content and ionic characteristics than on intersubject differences. Such early significant protein deposition may occur in wearers of disposable lenses as well as in those subject to complications due to accumulation of protein. PMID- 2205815 TI - Echobiometry in homocystinuria. PMID- 2205816 TI - Reticulohistiocytoma of the limbus and cornea. A clinicopathologic study of two cases. AB - Reticulohistiocytoma is a rare, benign histiocytic lesion usually occurring as an isolated skin nodule or as part of a systemic disorder known as "multicentric reticulohistiocytosis." The clinical and histopathologic findings of two women who presented with a single, painless mass localized to the cornea and limbus without skin lesions or systemic disease are reported. Histopathologically, the lesions were composed predominantly of large mononuclear and a few multinucleated cells with finely granular, "ground-glass" cytoplasm and large nuclei with prominent nucleoli. Immunohistochemical and electron microscopic studies conformed the histiocytic nature of these cells. Reticulohistiocytoma should be included in the differential diagnosis of epibulbar benign histiocytic lesions. PMID- 2205817 TI - Episcleritis, conjunctivitis, and keratitis as ocular manifestations of Lyme disease. AB - A 35-year-old woman presented with a bilateral palpebral follicular conjunctivitis. Subsequently, she developed a bilateral keratitis and, on a separate occasion, an episcleritis that was associated with a recrudescence of Lyme disease and poor compliance with the antibiotic regimen. Both the keratitis and episcleritis cleared completely after topical corticosteroid therapy and reinstitution of appropriate antibiotic treatment. This report emphasizes the importance of collaboration between internal medicine and ophthalmologic specialists during the long-term management of Lyme disease. PMID- 2205818 TI - [Markers of peripheral B lymphocytes and their function in IgA nephropathy]. AB - Peripheral blood B-lymphocyte markers and functions were observed in 21 patients with IgA nephropathy (IgA NP), 18 patients with systemic lupus erythematosus (SLE) and 16 controls. IgA NP B-lymphocytes similarly to that of SLE B lymphocytes expressed significantly higher positivity with Leu 1 (CD 5) monoclonal antibody than controls. CD 5 positive B-lymphocytes are thought to be a distinct subset of the B-cells (autoregulatory B-lymphocytes) inducible in IgA NP by lipopolysaccharide (LPS) stimulation in parallel to their expression of surface IgM heavy chain positivity. The activated state of IgA NP B-lymphocytes have been proved by their higher OKIa (HLA-DR) positivities but lower IOB1a (CD 21, C3b-receptor) and decreased IgG-Fc-receptor (ox- rosette) expression. IgA NP B-lymphocytes showed a higher IgA but also IgG and IgM polyclonal immunoglobulin production than control B-lymphocytes in co-cultures with T-lymphocytes. Not only regulatory T-lymphocyte subsets but also serum derived from IgA NP patients stimulated the immunoglobulin production of IgA NP B-lymphocytes. PMID- 2205819 TI - [First experiences with ultrasonic diagnosis using gastroenterologic endoscopy in Hungary]. AB - The authors were the first to gain experiences with gastroenterological endoscopic ultrasonography (EUS) in Hungary. Their examinations included the study of the esophageal wall and its environment as well as that of the stomach wall and the neighbouring organs. The construction of the instrument, the technique of the method and the indication for EUS are described on the basis of the authors' experiences and the literary data. They were the first to demonstrate perigastric effusion with EUS. On the basis of the observations it is stated that EUS is more reliable than other methods for the determination of the patency of varices following sclerotherapy. Thus this technique may improve the control of the efficacy of sclerotherapy in patients with portal hypertension. The authors wish to support their observation with prospective examination series carried out with high number of patients. PMID- 2205820 TI - [From the past of Hungarian-Spanish connections]. PMID- 2205821 TI - [Ferenc Liszt from the viewpoint of the dermatologist]. PMID- 2205822 TI - [Prognostic factors affecting survival in multiple myeloma]. AB - 70 patients suffering from multiple myeloma were observed by authors in the last 15 years and three months. In the meantime fifty-two out of them have died, and 18 patients are under permanent care. 43 IgG, 17 IgA, 6 Bence-Jones, 2 IgD types were diagnosed according to the paraprotein distribution, one patient proved to be nonsecretory, and an other one to osteosclerotic form as well. The median survival time was 27 months in the group of deceased patients. In the group followed-up 50.8 months survival time was observed up to the closing of the study. Several prognostic factors were investigated. According to the classification by Durie and Salmon the survival time was 60 months in the patients with stage I, 33 months in stage II., and 9 months in stage III respectively. The prognosis is much poorer in patients into the "B" category: the survival time was 14 months. Classified in the basis of the type of the myeloma cell, the cases with well matured cells have had the best prognosis with survival time of 46 months, while the most unfavourable prognosis was observed in patients with blast-cell type, with a median survival time of 10 months. The greatest number of patients suffered from multiple myeloma of IgG paraprotein type, in this group the serum IgA level was found to be significantly decreased in the patients died due to inevitable infections. The survival was injured significantly by the occurrence of concomitant severe diseases, to.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2205823 TI - [Contaminated small bowel syndrome in infants caused by gram-negative bacteria and yeasts]. AB - The upper small intestine is usually "sterile" in a healthy individuals, but due to some reasons the number of microorganisms may reach or increase above 10(4)/ml, leading to the contamination of the small intestine, which may cause severe malabsorption. The authors have diagnosed this syndrome in 50 children, aged between 1 month and 3 years, using breath hydrogen test and duodenal juice culture. Most of these children had growth retardation. According to their experience the authors found that the oral antibiotic is the effective treatment of this syndrome. PMID- 2205824 TI - [Thrombotic changes in hemostasis following streptokinase therapy in myocardial infarct]. AB - Thrombolytic treatment of acute myocardial infarction proved to be able to restore infarct artery patency and to decrease hospital mortality. The number of bleeding complications have remained at an acceptably low level, however some thromboembolic complications occurring during the first week following thrombolytic therapy have been recently observed. Signs of increased in vivo platelet activation (by measuring beta-thromboglobulin and thromboxane metabolite levels) and endothelial damage (Willebrand-factor estimations) could have been detected in our patients treated with brief high dose intravenous streptokinase, altogether with diminished antithrombin III and protein C antigen levels and activity. Intravenous streptokinase treatment of acute myocardial infarction might be able to cause thrombotic haemostatic alterations, which require meticulous haemostasis monitoring and early, correct antithrombiotic therapy. PMID- 2205825 TI - [Results of BCG immunotherapy in the management of bladder tumors]. AB - The authors reported their results of BCG immunotherapy in the treatment of the bladder cancer. between 1984-1989 60 superficial and 4 muscle infiltrative bladder tumors were treated. The results of 53 BCG treated superficial bladder cancer group were compared to control groups. The recurrence cases three-four times, the progressive cases eight-ten times were more in the control groups than it was found in the BCG group. They could not establish the value of BCG in the treatment of muscle infiltrative bladder cancer, because they had not appropriate number of patients and they could find only few articles in the literature. The authors surveied the last literature of BCG immuntherapy and verified that BCG had an important role in the treatment of the bladder cancer and searching the action of antitumor effect of BCG would add more useful information to cancer immunology. PMID- 2205826 TI - [Cricopharyngeal achalasia caused by isolated muscular dystrophy]. AB - The authors--in connection with two surgically successful treated cases--discuss the diagnosis and the surgical treatment of the cricopharyngeal achalasia. By means of histological methods it was verified that in the background of this disease stads an isolated muscle dystrophy localized to the upper esophageal sphincter. PMID- 2205827 TI - [Prenatal diagnosis of cystic fibrosis by analysis of microvillar enzymes of the amniotic fluid]. AB - Prenatal diagnosis was performed in 92 pregnancies high-risk for cystic fibrosis during six years. Amniotic fluid samples obtained by amniocentesis were examined with regard to their microvillar membrane enzyme activity. However, trehalase, alkaline phosphatase isoenzymes and L-gamma-glutamyl-transferase in the amniotic fluid are not specific markers of the cystic fibrosis, their activity is significantly lower than in normal pregnancies. By measuring the three enzymes simultaneously, sensitivity, specificity and reliability of the method were found to be over 92%. It is concluded that the mid-trimester amniotic fluid diagnosis is useful for some heterozygotic couples for cystic fibrosis even in the possession of the DNA methods. PMID- 2205828 TI - [Reconstruction of the oral and pharyngeal mucosa by a microsurgical method using a jejunal graft]. AB - The microsurgery is a new, modern method of the reconstructive surgery which has made the free transplantation of the jejunal graft possible. The jejunum transplanted with microvascular anastomosis lends itself mainly to replacing the segmental and concentrical defect of the initial part of the alimentary tract, but the splitted jejunal graft cut along the antimesenterical side, because of its favourable biological nature, can be used for reconstruction of the oral and pharyngeal mucosus membrane. The authors applied the splitted jejunal graft in four cases for the reconstruction of oropharyngeal defects due to excision of malignant tumours. In harmony with literary data good result is reported on. PMID- 2205829 TI - [The position of the AIDS Committee of the Ministry of Social and Health Services on the publication: Controversies Concerning AIDS, published in Medicus Universalis, No.6, 1989]. PMID- 2205830 TI - [King Mathias and the science of medicine in his time]. PMID- 2205832 TI - [In memory of Lorand Kesztyus (1915-1979)]. PMID- 2205831 TI - [Initial steps of experimental medicine in Hungary. Semmelweis, the medical student, in his laboratory]. PMID- 2205833 TI - Schistosoma mansoni: localization of the 28 kDa secreted protease in cercaria. AB - Monospecific rabbit antibodies were utilized to localize the 28 kDa serine protease which is released from transforming schistosomula of Schistosoma mansoni in cercariae and freshly transformed schistosomula. This protease exerts two postulated activities, degradation of connective tissue proteins thus promoting skin penetration and release of the cercarial glycocalyx leading to accelerated schistosomular transformation. Upon immunogold labelling of cercarial cryosections, the 28 kDa protease was found stored in both the preacetabular and postacetabular glands. This enzyme was also detected in the cercarial glycocalyx by immunogold and immunofluorescence labelling and by its proteolytic activity. Following transformation and shedding of the glycocalyx, the same 28 kDa protease was found on the surface membrane of transformed schistosomula which are resistant to immune damage. It is suggested that the 28 kDa membrane protease which cleaves in vitro the complement proteins C3, C3b and C9, may promote in vivo immunoresistance of S. mansoni. PMID- 2205835 TI - Frameshift suppression at tandem AGA and AGG codons by cloned tRNA genes: assigning a codon to argU tRNA and T4 tRNA(Arg). AB - Arginine is coded for by CGN (N = G, A, U, C), AGA and AGG. In Escherichia coli there is little tRNA for AGA and AGG and the use of these codons is strongly avoided in virtually all genes. Recently, we demonstrated that the presence of tandem AGA or AGG codons in mRNA causes frameshifts with high frequency. Here, we show that phaseshifts can be suppressed when cells are transformed with the gene for tRNA(T4Arg) or E. coli tRNA(argU,Arg) demonstrating that such errors are the result of tRNA depletion. Bacteriophage T4 encoded tRNA(Arg) (anticodon UCU) corrects shifts at AGA-AGA but not at AGG-AGG, suggesting that this tRNA can only read AGA. Similarly, comparison of the translational efficiencies in an argU (Ts) mutant and in its isogenic wild type parent indicates that argU tRNA (anticodon UCU) reads AGA but not AGG. An argU (Ts) mutant barely reads through AGA-AGA at 42 degrees C but translation of AGG-AGG is hardly, if at all, affected. Overexpression of argU+ relaxes the codon specificity. The thermosensitive mutant in argU, previously called dnaY because it is defective in DNA replication, can be complemented for growth by the gene for tRNA(T4Arg). This implies that the sole function of the argU gene product is to sustain protein synthesis and that its role in replication is probably indirect. PMID- 2205836 TI - The repair patch of E. coli (A)BC excinuclease. AB - The size of repair patch made by E. coli DNA polymerase I (Poll) following the removal of a thymine-psoralen monoadduct by E. coli (A)BC excinuclease was determined by using an M13mp19 DNA with a single psoralen monoadduct at the polylinker region. Incubation of this substrate with (A)BC excinuclease, Poll and a combination of 3 dnTP plus 1 dNTP(alpha S) for each nucleotide, and DNA ligase resulted in a repair patch with phosphorothioate linkages. The preferential hydrolysis of phosphorothioate bonds by heating in iodoethanol revealed a patch size--with minimal nick translation--equal in length to the 12 nucleotide gap generated by this excision nuclease. PMID- 2205837 TI - Solid phase in vitro mutagenesis using plasmid DNA template. AB - Site-specific mutagenesis was accomplished using a solid support to generate single stranded vector and insert fragments which can be used to form gap-duplex plasmids through flanking, complementary double stranded regions. More than 80% mutants were obtained in both a single and a double primer approach. No special vectors or strains are needed and mismatch repair is avoided as the mutagenesis region is in a single stranded form when transformed into the Escherichia coli host cell. The fragments to be immobilized can be produced either by a polymerase chain reaction using general primers or by a site-specific restriction followed by a fill-in reaction. This novel method is rapid, simple and flexible and well suited for both manual and semi-automated in vitro mutagenesis protocols. PMID- 2205834 TI - Searching for and predicting the activity of sites for DNA binding proteins: compilation and analysis of the binding sites for Escherichia coli integration host factor (IHF). AB - An analysis of the sequence information contained in a compilation of published binding sites for E. coli integration host factor (IHF) was performed. The sequences of twenty-seven IHF sites were aligned; the base occurrences at each position, the information content, and an extended consensus sequence were obtained for the IHF site. The base occurrences at each position of the IHF site were used with a program written for the Apple Macintosh computers in order to determine the similarity scores for published IHF sites. A linear correlation was found to exist between the logarithm of IHF binding and functional data (relative free energies) and similarity scores for two groups of IHF sites. The MacTargsearch program and its potential usefulness in searching for other sites and predicting their relative activities is discussed. PMID- 2205838 TI - Genetic evidence for similar negative regulatory domains in the yeast transcription activators GAL4 and LAC9. AB - The GAL4 protein of Saccharomyces cerevisiae and the LAC9 protein of Kluyveromyces lactis are transcription activator proteins with similar structure and function. Greatest similarity occurs in the C region near the carboxy terminus, where 16 of 18 amino acids are identical. The function of the C region is unclear. Here we show that the structural similarity is reflected in functional similarity. Single amino acid changes in the C region of GAL4 and LAC9 create a similar phenotype: constitutive gene expression. In S. cerevisiae the constitutive phenotype caused by GAL4 mutants can be abolished by overproduction of GAL80. These results support a model in which the C region of GAL4 and LAC9 constitute similar negative regulatory domains that interact with GAL80 in S. cerevisiae and an unidentified GAL80 homolog in K. lactis. This protein-protein interaction prevents expression of the galactose operon in the uninduced state. PMID- 2205839 TI - A ras-related gene from the lower eukaryote Dictyostelium that is highly conserved relative to the human rap genes. AB - The cellular slime mold Dictyostelium discoideum contains two ras genes, DdrasG and Ddras that are differentially expressed during development. We have characterized a gene that hybridized to both Ddras and DdrasG under low, but not under high stringency conditions. The deduced amino acid sequence is highly conserved with respect to the human rap (Krev-1, smg21) proteins and the corresponding gene has been designated Ddrap1. The Ddrap1 gene is expressed at all stages during development but is expressed maximally during the aggregation and culmination periods when the expression of Ddras and DdrasG is declining. During vegetative growth and early development Ddrap1 cDNA hybridizes to a single mRNA of 1.1 kb. As development progresses the level of this mRNA declines and messages of 1.0 and 1.3 kb appear. PMID- 2205840 TI - cDNA from rat cells with reconstitutive galactose-epimerase activity in E. coli. PMID- 2205841 TI - Characterization of Xenopus laevis cDNA clones of the c-ets-1 proto-oncogene. PMID- 2205843 TI - Single-step purification of shuttle vectors from yeast for high frequency back transformation into E. coli. PMID- 2205842 TI - A gene from S. pombe with homology to E. coli RNAse III blocks conjugation and sporulation when overexpressed in wild type cells. PMID- 2205844 TI - Plasmid DNA sequencing using highly degenerate oligonucleotides as primers. PMID- 2205845 TI - Boron trifluoride-methanol complex as a non-depurinating detritylating agent in DNA synthesis. PMID- 2205846 TI - An efficient method for isolation of promoter mutations after oligonucleotide directed mutagenesis. PMID- 2205847 TI - A rapid and reliable one-step method for isolating DNA fragments from agarose gels. PMID- 2205848 TI - Human hepatocytes in genotoxicity assays. AB - Human hepatocyte primary cultures, because of their comprehensive biotransformation capability, represent an experimental model particularly useful to gain direct information on the genotoxic risk of chemicals to humans. For this purpose they have been used in the last few years either as target cells to evaluate the induction of DNA damage and/or DNA repair synthesis, or as metabolic activation system in mutagenicity assays. The number of compounds so far tested is rather limited, and for the large majority of them the assays have been performed only on hepatocytes from a few donors. A comparison with the data obtained in rat hepatocytes indicates that quantitative differences in the genotoxic effects induced in cultures derived from different donors of the same species are usually greater than interspecies differences. However, the results.provided by some chemicals suggest the possibility that in certain cases rat hepatocytes might be inappropriate predictors of the genotoxic hazard for humans. PMID- 2205849 TI - Mononuclear cells from peripheral blood of adult donors and from cord blood are equally protected by alpha- and beta-interferons against infection with HTLV-I. AB - Human mononuclear cells derived from peripheral blood of adult donors (PBMC) or from neonatal cord blood (CBMC) were found to be equally sensitive to the protective effect of alpha- and beta-interferons (IFNs) against the infection with HTLV-I during long-term culture. The effect of IFNs was evidenced by a remarkable reduction of the number of virus-positive cells during culture as evaluated by indirect immunofluorescence for the p19 virus core protein. Moreover, the appearance of p19-positive immortalized clones was inhibited by IFNs in PBMC co-cultures, whereas it was delayed in CBMC cultures. These kinetics are in relation with the higher permissivity of CBMC to the virus in comparison with PBMC, since in CBMC cultures infected cells can be clearly detected starting already 1 week post-infection (p.i.), whereas in PBMC cultures their appearance time is approximately at the 6th week p.i. IFNs acted by 'priming' PBMC and CBMC to an active antiviral competence, since one single treatment with 1000 IU/ml of alpha- or beta-IFN at the onset of the co-culture of mononuclear cells with irradiated virus-donor cells was able to maintain very low levels of infection for approximately 6 weeks in CBMC cultures and at least for 18 weeks in PBMC cultures. As a consequence, it seems likely that IFN action is mediated by the expression of a defined, although not completely identified, set of genes in the host cells. PMID- 2205850 TI - Activity of synthetic tat peptides in human immunodeficiency virus type 1 long terminal repeat-promoted transcription in a cell-free system. AB - The tat protein encoded by the human immunodeficiency virus type 1 is a potent trans-activator of gene expression from the viral long terminal repeat. The domains that are essential for trans-activation, a Pro-Xaa3-Pro triad, a cysteine rich metal-binding sequence motif, and a cluster of basic residues, are present within the N-terminal 57 residues of tat. To determine the structural requirements for tat function and the role of metal binding at the transcription level alone, tat-(1-86) (full-length tat peptide), tat-(1-57), and tat-(1-47) were chemically synthesized. These peptides as well as the Cd2+ and Zn2+ complexes of tat-(1-86) and tat-(1-57) were evaluated for stimulation of transcription from the human immunodeficiency virus type 1 long terminal repeat by using cell-free in vitro methods. All three peptides produced a 7- to 9-fold increase over the basal level of transcription at a peptide concentration of 0.4 microM. Interestingly, at 4 microM, both tat-(1-57) and tat-(1-86) inhibited even the basal level of transcription. In contrast, tat-(1-47), which lacks the basic domain (residues 49-57), exhibited full stimulatory activity at 4 microM. Our data suggest, therefore, that the basic region may be responsible for the observed inhibitory activity of tat-(1-86) and tat-(1-57). Furthermore, binding to Zn2+ and not to Cd2+ ions only slightly augments (approximately 2-fold) the activity of the tat peptides. PMID- 2205852 TI - Structure-function studies on Escherichia coli MetR protein, a putative prokaryotic leucine zipper protein. AB - The Escherichia coli metR gene has been sequenced. The sequence predicts a protein of 317 amino acids and a calculated molecular weight of 35,628. This is about 15% larger than the protein from Salmonella typhimurium reported previously [Plamann, L.S. & Stauffer, G.V. (1987) J. Bacteriol. 169, 3932-3937]. The protein is a homodimer and contains a leucine zipper motif characteristic of many eukaryotic DNA-binding proteins. Replacement of two of the leucines in the leucine zipper region of the MetR protein, or substitution of proline for one of the leucines, results in loss of biological activity of the protein. In addition, truncation studies have identified a region on MetR that may be involved in the homocysteine activation of metE expression. PMID- 2205851 TI - Abnormally high expression of proteasomes in human leukemic cells. AB - Proteasomes are eukaryotic ring-shaped or cylindrical particles with multicatalytic protease activities. To clarify the involvement of proteasomes in tumorigenesis of human blood cells, we compared their expression in human hematopoietic malignant tumor cells with that in normal peripheral blood mononuclear cells. Immunohistochemical staining showed considerably increased concentrations of proteasomes in leukemic cells from the bone marrow of patients with various types of leukemia and the predominant localization of these proteasomes in the nuclei. Moreover, enzyme immunoassay and Northern blot analysis indicated that the concentrations of proteasomes and their mRNA levels were consistently much higher in a variety of malignant human hematopoietic cell lines than in resting peripheral lymphocytes and monocytes from healthy adults. Proteasome expression was also greatly increased in normal blood mononuclear cells during blastogenic transformation induced by phytohemagglutinin; their expression increased in parallel with induction of DNA synthesis and returned to the basal level with progress of the cell cycle. Thus, abnormally high expression of proteasomes may play an important role in transformation and proliferation of blood cells and in specific functions of hematopoietic tumor cells. PMID- 2205853 TI - Prolonged inhibition of luteinizing hormone and testosterone levels in male rats with the luteinizing hormone-releasing hormone antagonist SB-75. AB - Inhibitory effects of the potent antagonist of luteinizing hormone-releasing hormone N-Ac-[3-(2-naphthyl)-D-alanine1,4-chloro-D-phenylalanine2,3- (3-pyridyl) D- alanine3,D-citrulline6,D-alanine10]luteinizing hormone-releasing hormone (SB 75) free of edematogenic effects were investigated in male rats. In a study to determine the effect on luteinizing hormone levels in castrated male rats, SB-75 was injected s.c. in doses of 0.625, 1.25, 2.5, 5.0, and 10 micrograms. Blood samples were taken at different intervals for 48 hr. All doses of SB-75 significantly decreased luteinizing hormone levels for greater than 6 hr (P less than 0.01); this inhibition lasted for greater than 24 hr (P less than 0.01) with a dose of 5.0 micrograms and greater than 48 hr with 10 micrograms (P less than 0.05). Serum testosterone levels were also measured in intact male rats injected with SB-75 in doses of 25, 50, and 100 micrograms. All doses produced a dramatic fall in testosterone to castration levels 6 hr after injection (P less than 0.01); this inhibition of serum testosterone was maintained for greater than 72 hr, but only the 100-micrograms dose could keep testosterone in the castration range for greater than 24 hr (P less than 0.01). In another study using a specific RIA, we obtained the pharmacokinetic release pattern of SB-75 from two sustained delivery formulations of SB-75 pamoate microgranules and examined their effect on serum testosterone. After a single i.m. injection of 20 mg of one batch of microgranules, a large peak corresponding to SB-75 at 45.8 ng/ml was observed, corresponding to the "burst" effect. Levels of the analog decreased to 19.6 ng/ml on day 2, gradually reached a concentration of 4.7 ng/ml on day 7, and kept declining thereafter. Testosterone levels were reduced on day 1 (P less than 0.01) and were maintained at low values for greater than 7 days (P less than 0.05). In rats injected with 10 mg of SB-75 pamoate microgranules of the second batch, SB-75 serum levels rose to 33 ng/ml 3 hr after administration and then fell gradually to approximately 3.4 ng/ml on day 16, but a second small peak was seen on day 28. Subsequently, the analog levels decreased slowly to 2.9 ng/ml on day 42. At this time, testosterone serum levels were still significantly lower than in controls. These overall results demonstrate the efficacy of SB-75 in the suppression of the pituitary-gonadal axis. This modern luteinizing hormone releasing hormone antagonist can possibly be used for treating sex hormone sensitive cancers and other disorders. PMID- 2205854 TI - Dominant negative umuD mutations decreasing RecA-mediated cleavage suggest roles for intact UmuD in modulation of SOS mutagenesis. AB - The products of the SOS-regulated umuDC operon are required for most UV and chemical mutagenesis in Escherichia coli. The UmuD protein shares homology with a family of proteins that includes LexA and several bacteriophage repressors. UmuD is posttranslationally activated for its role in mutagenesis by a RecA-mediated proteolytic cleavage that yields UmuD'. A set of missense mutants of umuD was isolated and shown to encode mutant UmuD proteins that are deficient in RecA mediated cleavage in vivo. Most of these mutations are dominant to umuD+ with respect to UV mutagenesis yet do not interfere with SOS induction. Although both UmuD and UmuD' form homodimers, we provide evidence that they preferentially form heterodimers. The relationship of UmuD to LexA, lambda repressor, and other members of the family of proteins is discussed and possible roles of intact UmuD in modulating SOS mutagenesis are discussed. PMID- 2205855 TI - Introduction of exogenous growth hormone receptors augments growth hormone responsive insulin biosynthesis in rat insulinoma cells. AB - The stimulation of insulin biosynthesis in the pancreatic insulinoma cell line RIN5-AH by growth hormone (GH) is initiated by GH binding to specific receptors. To determine whether the recently cloned rat hepatic GH receptor is able to mediate the insulinotropic effect of GH, we have transfected a GH receptor cDNA under the transcriptional control of the human metallothionein promoter into RIN5 AH cells. The transfected cells were found to exhibit an increased expression of GH receptors and to contain a specific GH receptor mRNA that was not expressed in the parent cell line. The expression of GH receptors in one clone (1.24) selected for detailed analysis was increased 2.6-fold compared to untransfected cells. The increased GH receptor expression was accompanied by an increased responsiveness to GH. Thus, the maximal GH-stimulated increase of insulin biosynthesis was 4.1 fold in 1.24 cells compared to 1.9-fold in the nontransfected RIN5-AH cells. The expression of the transfected receptor was stimulated 1.6- and 2.3-fold when cells were cultured in the presence of 25 or 50 microM Zn2+, respectively. The increased expression of the GH receptor by Zn2+ was associated with an increased magnitude of GH-stimulated insulin biosynthesis. A close stoichiometric relationship between the level of receptor expression and the level of GH stimulated insulin biosynthesis was observed. We conclude from these results that the hepatic GH receptor is able to mediate the effect of GH on insulin biosynthesis in RIN5-AH cells. PMID- 2205858 TI - Role of stromal cell factors (restrictins) in microorganization of hemopoietic tissues. PMID- 2205857 TI - Stromal regulation of hemopoiesis. PMID- 2205856 TI - Growth of Plasmodium falciparum in human erythrocytes containing abnormal membrane proteins. AB - To evaluate the role of erythrocyte (RBC) membrane proteins in the invasion and maturation of Plasmodium falciparum, we have studied, in culture, abnormal RBCs containing quantitative or qualitative membrane protein defects. These defects included hereditary spherocytosis (HS) due to decreases in the content of spectrin [HS(Sp+)], hereditary elliptocytosis (HE) due to protein 4.1 deficiency [HE(4.1(0))], HE due to a spectrin alpha I domain structural variant that results in increased content of spectrin dimers [HE(Sp alpha I/65)], and band 3 structural variants. Parasite invasion, measured by the initial uptake of [3H]hypoxanthine 18 hr after inoculation with merozoites, was normal in all of the pathologic RBCs. In contrast, RBCs from six HS(Sp+) subjects showed marked growth inhibition that became apparent after the first or second growth cycle. Preincubation of HS(Sp+) RBCs in culture for 3 days did not alter these results. Normal parasite growth was observed in RBCs from one HS subject with normal membrane spectrin content. The extent of decreased parasite growth in HS(Sp+) RBCs closely correlated with the extent of RBC spectrin deficiency (r = 0.90). Homogeneous subpopulations of dense HS RBCs exhibited decreased parasite growth to the same extent as did HS whole blood. RBCs from four HE subjects showed marked parasite growth inhibition, the extent of which correlated with the content of spectrin dimers (r = 0.94). RBCs from two unrelated subjects with structural variants of band 3 sustained normal parasite growth. Decreased growth in the pathologic RBCs was not the result of decreased ATP or glutathione levels or of increased RBC hemolysis. We conclude that abnormal parasite growth in these RBCs is not the consequence of metabolic or secondary defects. Instead, we suggest that a functionally and structurally normal host membrane is indispensable for parasite growth and development. PMID- 2205859 TI - In vitro regulation of human megakaryocyte maturation. PMID- 2205860 TI - The mechanism of action of murine interleukin-3: current status. PMID- 2205861 TI - Structure and function of interleukin-2 receptors. PMID- 2205862 TI - Phorbol esters, lipopolysaccharides and colony stimulating factor production. PMID- 2205863 TI - The regulation of hematopoiesis in the human fetal liver. PMID- 2205864 TI - Interleukin-1 stimulation stabilizes GM-CSF mRNA in human vascular endothelial cells: preliminary studies on the role of the 3' AU rich motif. AB - To date, the notion that the AU rich motif in the 3' UT of GM-CSF mRNA can function as an IL-1 response element has not been adequately examined. We suspect that it must play some role because virtually all IL-1 inducible gene have AU rich 3' untranslated regions. Thus, we will continue to address these technical problems so that the hypothesis can be more clearly tested. Nonetheless, we can state with reasonable certainty that: 1) IL-1 induces expression of GM-CSF in EC by inducing accumulation of mRNA, 2) the GM-CSF gene is constitutively transcribed but the half life of the mRNA is short, 3) IL-1 induced mRNA accumulation results from stabilization of the transcript, 4) although most IL-1 responsive genes have AU-rich domains in their 3' untranslated regions, it is not yet clear that these AU-rich regions are sufficient to function as an IL-1 response element, and 5) murine L cells cannot be used for studies on the molecular biology of cytokine induction by IL-1. PMID- 2205865 TI - Control of hematopoietic growth factors. PMID- 2205866 TI - Cytogenetic and molecular analysis of the deletions of chromosome 5 in myeloid disorders. PMID- 2205867 TI - Characterization of human hematopoietic stem cells. AB - These data clearly indicate that suitable systems are presently available to isolate the human hematopoietic stem cell. The CFU-B1 and cells responsible for initiating long term hematopoiesis in vitro are likely identical since they share the same phenotype, CD34+DR-CD33-CD15-C71-. The suspension culture system as indicated above has several advantages over an adherent cell based long term marrow culture system. Use of this suspension culture system with 48 hourly feeding with recombinant cytokines will facilitate definition of the cytokine requirements for the human CFU-S. PMID- 2205868 TI - Human gene therapy--playing God? PMID- 2205869 TI - An ethical analysis of gene therapy as molecular surgery. PMID- 2205870 TI - Ethical considerations regarding potentials of human gene therapy: ethical dilemmas in serendipity. PMID- 2205871 TI - Some observations on the growth requirements of multipotent stem cells under defined culture conditions. PMID- 2205873 TI - Radioprotection and therapy of radiation injury with cytokines. AB - Our results demonstrate that IL 1 promotes hematopoiesis in normal and radiation compromised animals. IL 1 protected mice from lethal hematopoietic syndrome when given before irradiation. Given therapeutically after irradiation, IL 1 promoted recovery from radiation injury. Several activities of IL 1 may explain its bone marrow restorative properties. The induction with IL 1 of several hematopoietic growth factors (GM-CSF, G-CSF, M-CSF, IL 3, and IL 6) clearly contributes to the accelerated growth and differentiation of hematopoietic progenitor cells. The induction of scavenger proteins may reduce oxidative damage after irradiation. Our work raises a number of additional questions concerning the potential therapeutic utility of IL 1. The ability of IL 1 to promote engraftment of allogeneic bone marrow cells will require further study. The optimal dosage, schedule, and route for IL 1 induction of hematopoiesis will need to be established. The observed synergy of IL 1 with TNF, IL 6, or CSF's may be useful in reducing the requisite doses of cytokines from pharmacological to physiological levels, thus reducing toxic effects. The observation that the cyclooxygenase inhibitor, indomethacin, does not inhibit IL 1 radioprotection may allow us to combat some of the toxic manifestations of IL 1 and to preserve its beneficial actions. Clinical trials with IL 1 in patients, now in progress, should establish whether this cytokine may be useful in reversing the myelotoxic effects of radiotherapy and chemotherapy in humans. PMID- 2205872 TI - Is natural background or radiation from nuclear power plants leukemogenic? AB - In view of the enormous number of base pair replications per annum in hemopoietic stem cells with the likelihood of coding errors, the rarity of the leukemogenic event at the cellular level after high doses of radiation, the infrequent occurrence of radiation events in cells at low-level exposure (large fraction of cells uninvolved), biological protective mechanisms and the realization that exposure of human populations to radiation from nuclear power plants is a very small fraction of natural radioactivity and will for the foreseeable future remain small and that populations exposed to high natural background radiation show no detectable harmful effects, it is concluded that either there is no effect, or for statistical reasons one cannot detect an effect. PMID- 2205874 TI - Cell membrane family of growth regulatory factors. AB - Both negative and positive regulators of cell growth and differentiation have been found in association with the surface of a variety of cell types, including fibroblasts, lymphocytes, undifferentiated components of the slug, neuronal cells, monocytes and mesenchymal cells (see Table 3). These molecules have been implicated in mediating contact inhibition, suppression of lymphopoiesis, inhibition of DNA synthesis in erythroid progenitors, induction of differentiation in Dictyostelium, stimulation of Schwann cell proliferation, and stimulation of the proliferation of a variety of hematopoietic cells, including myeloid (Price et al, 1975), erythroid and macrophage progenitor cells. In some cases, families of membrane bound growth factors have been described or are currently being appreciated. The importance of cell surface-associated regulators in mediating close cell-cell interactions in vitro and in vivo as well is under active investigation. PMID- 2205875 TI - The use of recombinant human erythropoietin [rHuEpo] in man. PMID- 2205876 TI - Membrane bound forms of human macrophage colony stimulating factor (M-CSF, CSF 1). PMID- 2205877 TI - A protein (NRP) that negatively regulates erythroid stem cell proliferation: antagonism to IL-3 stimulation. PMID- 2205878 TI - Vitamin E and platelet eicosanoids in diabetes mellitus. PMID- 2205879 TI - [Protease-catalyzed synthesis of peptides in biphasic aqueous-organic systems]. PMID- 2205880 TI - [Biochemical basis of pharmaceutical chemistry. 7. Drugs for maintenance of calcium-, fluid volume- and blood sugar homeostasis]. PMID- 2205881 TI - [Two problems concerning mental health policy]. PMID- 2205882 TI - [Height vertigo, fear of heights, acrophobia]. AB - Height vertigo (acrophobia) is a very frequent phenomenon being of interest for its physiological and psychological background, though usually only of limited significance in neuropsychiatry and otology. The different aspects as to its nature and origin are discussed. If acrophobia has developed into a conditioned reaction of avoidance with pressure of suffering, or acrophobia in persons, who have to work at heights, behavior therapeutic measures with systematic desensibilisation, starting from an imaginative training, are indicated. PMID- 2205883 TI - [The 1789 French Revolution and reform of mental health services for the insane in France]. PMID- 2205884 TI - [X-ray diagnosis of immunologically induced lung diseases in children and adolescents]. AB - After coverage of pathophysiological mechanisms, radiological symptoms and differential diagnosis of bacterial and opportunistic infections of the bronchopulmonary system are discussed as they occur in humoral, cellular and combined congenital and acquired immune deficiencies. The discussion is based on case reports. Humoral deficiencies cause recurrent and chronic bacterial infections of the bronchopulmonary system, frequently with bronchiectasis. In the case of cellular and combined immune deficiencies, not only bacterial infections but also the very serious opportunistic infections occur. Opportunistic infections of the lung are predominantly caused by Pneumocystis carinii, by the cytomegaly virus, and by fungi such as Candida, Aspergillus and Mucor. Pneumocystis is also the most frequent cause of opportunistic infections of the lungs in children with AIDS. In contrast to the situation in adults, in children a relatively low-grade lymphocytic interstitial pneumonitis occasionally precedes the typical opportunistic infections. Lymphocytic interstitial pneumonitis and Pneumocystis pneumonia can be differentiated from each other easily in children because of their relatively characteristic appearances. Fungal infections, on the other hand, sometimes pose severe diagnostic problems. Radiological chest findings in autoimmune diseases are discussed. PMID- 2205885 TI - [Differential diagnosis of inflammatory lung diseases in childhood]. AB - The response to lower airway infection in childhood is different from that in later life. Agent-specific reactions and the age of the child have to be considered in differential diagnosis. Indicators of a bacterial or a viral etiology of the pulmonary findings are often present. However, in some cases the etiology cannot be determined because mixed infections are present. Furthermore, the roentgenographic findings in viral pneumonia may mimic the signs of bacterial infection. Age-specific radiographic findings in pulmonary infections are discussed. PMID- 2205886 TI - [Radiologic findings and differential diagnosis of bronchial asthma in childhood]. AB - In children with asthma, routine chest X-ray typically shows bilaterally increased air volume, low diaphragms, wide diaphragmatic angles, and often a slender cardiac silhouette with a prominent pulmonic arch. Such an X-ray is not diagnostic of asthma itself, however, but rather of its complications: pneumonitis (particularly in toddlers with infectious asthma), atelectasis due to mucus obstruction, and, rarely, extra-alveolar air trapping (pneumomediastinum with or without cutaneous emphysema more often than pneumothorax). The differential diagnosis has to rule out "pseudo asthma" due to cystic fibrosis, alveolitis, achalasia, and foreign body aspiration. PMID- 2205887 TI - [X-ray signs of foreign body aspiration in children]. AB - Preoperative chest X-rays were taken in both postanterior and partially lateral views of 94 children with foreign-body aspiration. Additional fluoroscopy was employed in 70 patients. In 7% of the cases, the foreign body was radiopaque; in an equal amount of cases, there were no radiological findings. In the remaining results we observed: emphysema as an indirect radiological sign in two-thirds of the cases; in less than one-third, poststenotic atelectasis; pneumonia in 10%; bronchitis in 9%; pneumothorax in 2%. PMID- 2205888 TI - [Tuberculous spondylitis following BCG vaccination]. AB - A case of a rare form of BCG osteomyelitis in the spine is presented. After vaccination, the disease started with a lymphadenitis. Later an abscess extended from the pelvic along the psoas muscles into the retroperitoneum. The soft tissue mass extended paraspinally and epidural involvement was also apparent. The vertebral involvement was detected by CT. The radiological findings are discussed with reference to the literature. PMID- 2205889 TI - [The effect of sonography on the therapeutic outcome in posttraumatic, postoperative and inflammatory soft tissue lesions]. AB - A total of 135 patients with a suspected diagnosis of post-traumatic, postoperative or inflammatory soft-tissue lesions were examined by ultrasound. The majority of patients (n = 48) showed post-traumatic soft-tissue hematomas with or without muscle rupture. Post-operative hematomas were found in 23 and hematomas after anticoagulation therapy in 4 patients. Inflammatory soft-tissue lesions were diagnosed in 14 patients and inflammatory tendon lesions in 16. The ultrasonographic diagnoses and therapeutic consequences were compared retrospectively. Therapeutic management was based upon the clinical signs and sonographic findings. Ultrasonically guided needle aspiration is of diagnostic value and is performed as a therapeutic modality as well. PMID- 2205890 TI - [Macrophage scavenger receptor]. PMID- 2205891 TI - [Protective immunity against infections]. PMID- 2205893 TI - Solubilities of pesticide chemicals in water. Part II: Data compilation. PMID- 2205892 TI - Solubilities of pesticide chemicals in water. Part I: Environmental physical chemistry. AB - It is hoped that this review of the equilibrium aqueous solution thermodynamics and environmental partitioning tendencies of chemicals will be valuable in elucidating the behavior of pesticide chemicals in the environment and in promoting the development of more reliable correlations between physical chemical measurements and environmental partitioning coefficients. Ultimately the success of both the thermodynamic and environmental interpretations depend on having reliable, critically reviewed data from both laboratory and the "field." PMID- 2205894 TI - Cutis marmorata telangiectatica congenita associated with bilateral congenital retinal detachment. AB - Cutis marmorata telangiectatica congenita is a rare congenital vascular disorder of the skin, characterized by persistent telangiectasia of the cutaneous blood vessels often associated with cutaneous ulcers. The only previously recognized ophthalmic association with this condition has been rare instances of unilateral congenital open angle glaucoma. The authors report their observations in a child in whom this cutaneous disorder was associated with congenital bilateral total retinal detachments and secondary neovascular glaucoma. The retinal detachments produced bilateral leukocoria simulating retinoblastoma. The cutaneous disorder and the ocular findings were confirmed histopathologically. PMID- 2205895 TI - From whence cometh this dread pestilence? PMID- 2205896 TI - 5-Hydroxytryptamine: new receptors and novel drugs for gastrointestinal motor disorders. PMID- 2205897 TI - Experimental pathogenesis: drugs and chemical lesions in the gastric mucosa. AB - The goals of this article are to review the similarities and differences in the pathogenesis of acute gastric mucosal injury induced by alcohol, exemplified mostly by ethanol, and aspirin, as a representative of nonsteroidal anti inflammatory drugs, and to deduce implications from pathogenetic studies for a better understanding of the concept of gastric cytoprotection. The main similarity between the hemorrhagic erosions caused by ethanol and aspirin is their localization in the acid-producing glandular stomach, the rate-limiting step in their pathogenesis being the extent of microvascular injury in the gastric mucosa. The major differences include the fast healing and low probability of transition into chronic gastritis after a single exposure to aspirin. On the other hand, perforated ulcer may develop, especially in the elderly, after chronic aspirin but not ethanol consumption. The main implications of pathogenetic investigations include the relative nature of gastroprotection: that is, initially, the superficial epithelial layer is not protected against concentrated luminal solutions, but it is rapidly replaced by migrating, adjacent, surviving cells if blood flow is maintained and the basement membrane is relatively intact. Vascular changes thus seem to be the rate-limiting step both in the pathogenesis and prevention of chemically induced acute gastric mucosal injury. The ultimate biochemical mechanisms of gastroprotection seem to include an effect on structural and enzymic proteins, and vascular mediators which influence vascular permeability and, indirectly, the extent of tissue injury. PMID- 2205898 TI - Mechanisms of gastroprotection. AB - Gastric mucosa is constantly exposed to various irritants, but it usually maintains its integrity owing to several lines of defense, including mucus alkaline secretion, mucosal hydrophobicity, rich mucosal blood flow, stabilization of tissue lysosomes, maintenance of mucosal sulfhydryls, and rapid proliferation and renewal of mucosal cells. Prostaglandins (PG) inhibit experimental gastric mucosal damage and ulcerations induced by a wide variety of agents, hence PG have been proposed to contribute to the overall protective process by activation of various mucosal defence lines--particularly by prevention of vasocongestion, ischemia, and deep hemorrhagic necrosis. The relation between tissue PG generation and mucosal protection does not appear to be closely related, and probably only minute amounts of PG are required to maintain mucosal integrity. In contrast to PG, other products of arachidonate metabolism, such as TxA2, LTC4 or LTD4, and the related lipid, platelet activating factor, appear to mediate mucosal damage mainly by the disturbance in mucosal microcirculation and tissue ischemia. Gastroprotection can be achieved by stimulation of mucosal biosynthesis of protective PG or by the inhibition of the release or action of the proulcerogenic arachidonate metabolites. Certain natural substances, such as sulfhydryls, epidermal growth factor, or polyamines, protect the mucosa via a PG-independent mechanism, probably by enhancing the tissue repair processes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2205899 TI - Antacids in gastric ulcer treatment: evidence of cytoprotection. AB - Antacids are more effective than placebo, and their efficacy is comparable to that of H2-blockers in gastric ulcer healing even though the healing time is about 2 weeks longer than with H2-blockers. Some observations in animals and healthy subjects may indicate that antacids (particularly those containing aluminium hydroxide) have a protective effect on the gastroduodenal mucosa in that they increase the production of prostanoids and sulphydryl-containing compounds. We showed that 10 days' treatment with high-dose antacids (Maalox TC) is able to increase 6-keto-PGF1 alpha production from cultured biopsy specimens of patients with gastric ulcer. These data could constitute a further indication in the treatment of peptic disease. PMID- 2205900 TI - Antacids for duodenal ulcer: current role. AB - Recent years have witnessed significant progress in antacid therapy of duodenal ulcer disease, consisting in the demonstration that the doses required for ulcer healing are much smaller and less frequent that those regarded as necessary or optimal in the past. Antacids at these dosages proved to be as effective as H2 blockers both in terms of healing capacity and in relieving ulcer symptoms and are associated with negligible gastrointestinal side-effects. In addition, there has been a renewed interest in the tablet formulation, which now appears more acceptable to the patient. All these characteristics make antacids competitive with other anti-ulcer agents, especially in terms of the cost/benefit ratio. PMID- 2205901 TI - Maintenance of duodenal ulcer healing by antacids. AB - Three studies have investigated the ability of long-term antacid treatment to prevent duodenal ulcer relapse. The first of these, more than 30 years ago, showed that antacids could reduce recurrence or persistence of symptoms when compared with placebo. There are two studies from the 'modern era' of fibreoptic endoscopy and H2-reception antagonists. The Milan study found antacid (one tablet four times daily), cimetidine (400 mg at night), or a combination of the two, to be approximately equally effective in the prevention of relapse. The international study found antacid (three tablets three times daily) to be as effective as cimetidine (400 mg at night) and to be better than placebo for maintenance purposes. Antacid, three tablets at night had intermediate efficacy. PMID- 2205902 TI - Antacids: new perspectives in cytoprotection. AB - There is increasing evidence that aluminum-containing antacids are able to protect the gastric mucosa against various ulcerogenic and necrotizing agents including 0.6 M HCl, 0.2 M NaOH, and absolute alcohol. Since gastric mucosal necrosis produced by alcohol is independent of luminal acid and cannot be reduced by H2-receptor antagonists, the protective action of antacids is accomplished by mechanism(s) other than acid-neutralizing ability. In addition, since acidified antacids can protect the gastric mucosa even better than an antacid with intact neutralizing capacity, it is clear that such action is independent of acid neutralizing ability and therefore has all the features of cytoprotection. Whereas the cytoprotective action of antacids in experimental conditions is well established, the mechanisms of antacid-induced mucosal protection are not known. The clinical relevance of antacid-induced protection also requires further elucidation. Antacids have advantages over the H2 blockers in protecting the gastric mucosa against alcohol-induced necrosis and in preventing stress-induced ulcers in critically ill patients. Although more work is needed to clarify the mechanisms of cytoprotective action of antacids, the recent experimental findings gave a new life to and new potential clinical applications for antacids. PMID- 2205903 TI - Leucocyte adhesion to cells. PMID- 2205904 TI - Neutrophil beta-2 microglobulin: an inflammatory mediator. AB - Beta-2 microglobulin (beta 2m) constitutes the light invariant chain of HLA class I antigen, and is a constituent of mobilizable compartments of neutrophils. Two forms of beta 2m exist: native beta 2m and proteolytically modified beta 2m (Des Lys58-beta 2m), which shows alpha mobility in crossed radioimmuno electrophoresis. The modification of native beta 2m can be executed by membrane associated activity of mononuclear cells, and Des-Lys58-beta 2m augments the production of interleukin 2. In this study we present evidence that human neutrophils contain native beta 2m in specific granules, secretory vesicles, and plasma membrane. Beta 2m was released in the native form from neutrophils in response to stimulation with chemotactic stimuli and phorbol ester. The results of experiments designed to study the modification of native beta 2m by neutrophils indicated that neutrophils do not participate in the proteolysis of beta 2m. However, we demonstrated that native beta 2m following degranulation may be transformed to Des-Lys58-beta 2m by lymphocytes. We suggest that neutrophil beta 2m following exocytosis may be transformed to Des-Lys58-beta 2m, acting as an extracellular messenger between granulocytes and lymphocytes in the inflammatory focus. PMID- 2205905 TI - Muscle function in rheumatoid arthritis. Assessment and training. AB - The conclusions can be summarized as follows: experienced problems of muscle function were reported in about 80% of RA and OA patients for whom there was involvement of large joints of the lower extremities; RA and OA patients did not differ as to experienced problems of muscle strength, endurance and balance/coordination; problems of muscle function were correlated with functional tests of muscle strength but not with those of endurance and balance/coordination; problems of muscle strength were found to correlate with LE ADL, whereas problems of endurance and balance/coordination were not found to correlate with the latter; the translated and slightly modified version of the HAQ questionnaire appeared to possess a high degree of reliability and validity in assessing disability in patients with RA under Swedish conditions; a quantitative battery of tests for the evaluation of standing balance on a computerized force platform was found to be satisfactorily reliable and to correlate in healthy subjects with most of the functional tests employed; in healthy subjects, standing balance appeared to be related not only to age but also to sex, males and older age groups showing greater postural sway than females and persons of younger age groups; compared with healthy subjects, RA subjects showed significantly greater postural sway, differences being greatest for those tests representing a relatively high level of difficulty; dynamic training for six weeks appeared to provide RA patients with a greater increase in physical capacity of the lower extremities than did static training, the gains thus obtained still being present after an additional three-month period; the effectiveness of the dynamic training programs did not vary with the degree of supervision of training by a physiotherapist, i.e. of 12 visits or 4 being made at the health care centre; despite the intensity of the dynamic training-program employed with RA patients, no increase in pain experience or disease activity was found during the training-period; during short-term high-intensity training a significant increase in circulating beta-EP was found between the 3rd and 6th weeks of training, no increase in CRF and beta-LPH being present; following a long-term low-intensity training period, a significant increase of CRF and beta LPH was found, no similar increase being noted for beta-EP. PMID- 2205906 TI - Immunohistopathologic findings in synovial biopsies before and after synovectomy in patients with chronic inflammatory joint diseases and their relation to clinical evaluation. A prospective study of biopsies taken from areas selected by arthroscopy. AB - Synovial biopsies were obtained from 28 patients with various kinds of chronic arthritis, at synovectomy and 6 and 12 months later. The tissues were examined by immunofluorescence technique, recording the quantities of cells and extracellular deposits staining with polyclonal antisera to IgG, IgA, IgM, C3c, fibrinogen, and chi and lambda light chains, and monoclonal antibodies to CD3, CD5, CD11b, HLA DR, and TCC (Terminal Complement Complex). These parameters were compared with scores obtained by arthroscopy and clinical evaluation (Colorado Knee Score) performed at the same time. Taken as a group, the immunological parameters showed reduction in activity 6 months after synovectomy (p less than 0.01), and a tendency to revert to base-line values after 12 months. A similar reduction in activity after 6 months was also found by arthroscopic and clinical evaluation. Thus, this longitudinal study demonstrated a relationship between changes in immunologic activity, arthroscopic findings and clinical activity after synovectomy in patients with chronic arthritis. This is consistent with an immunological pathogenesis for the inflammation in these joints. PMID- 2205907 TI - Clinical and laboratory outcomes during the treatment of rheumatoid arthritis with methotrexate. AB - Ten clinical and three laboratory outcomes were evaluated in 86 patients completing a double-blind placebo-controlled trial of methotrexate in rheumatoid arthritis. The improvement in all measured outcomes was statistically significantly better in patients receiving methotrexate than in patients receiving placebo. The correlations of the changes in outcome measures were calculated to determine if improvement in one parameter was associated with improvement in other clinical parameters. Associations between different clinical outcomes were often statistically significant. Associations between laboratory outcomes were also often statistically significant. However, the association between clinical outcomes and laboratory outcomes was generally poor. PMID- 2205908 TI - Morphology of polyanhydride microsphere delivery systems. AB - Scanning electron microscopy (SEM) was used to elucidate the mechanism of polymer degradation and drug release in polyanhydride microspheres. Three different fabrication methods--solvent removal, solvent evaporation, and hot melt microencapsulation--were used to prepare polyanhydride microspheres containing a variety of drugs. The morphology of these microspheres releasing drug in vitro and in vivo was studied by SEM and compared with degradation and release data measured by conventional methods. Microspheres prepared by the three techniques were shown to have distinctive morphological characteristics induced by the nature of the fabrication method. In addition, SEM analysis could be used to explain the drug release profiles and polymer degradation behavior seen in vitro as well as the in vivo effects of insulin-loaded microspheres on diabetic rats. This study has shown SEM to be an important and powerful tool for analyzing the effects of microsphere fabrication method on drug release. PMID- 2205909 TI - Healing of prosthetic arterial grafts. AB - Numerous synthetic biomaterials have been developed as vascular substitutes. In vitro, ex vivo and in vivo studies have demonstrated that in animals, selected materials, i.e., Dacron and ePTFE (expanded polytetrafluoroethylene) grafts, are successfully incorporated in both the large and the small caliber host arteries through a process which is generally referred to as graft healing. Morphologically, this process consists of a series of complex events including fibrin deposition and degradation, monocyte-macrophage recruitment and flow oriented cell-layer generation, this last event being the complete endothelialization of the arterial substitute. In contrast to experimental animals, the flow surface of synthetic vascular grafts remains unhealed in humans, particularly in the small caliber conduits. Healing in man consists of graft incorporation by the perigraft fibrous tissue response with a surface covered by more or less compacted, cross-linked fibrin. It is therefore obvious that: i) marked differences in graft healing exist between animals and man; and ii) the usual mechanisms of graft endothelialization are partially ineffective in man. In order to guarantee the patency of synthetic vascular grafts for human small artery bypass, new strategies and approaches have recently been attempted. In particular, the endothelial cell seeding approach has been successfully accomplished in animals and is being experimented in human clinical studies. The problems and results of this biological approach are outlined in this paper. PMID- 2205910 TI - The state of potassium in skeletal muscle and in non-muscle cells. AB - The relationship between ions, water, and the electrical properties are fundamental to our understanding of cellular function. This paper is primarily directed at reviewing the theoretical explanations for the changes in cellular potential and ionic composition which are associated with early postnatal development of skeletal muscle. The findings are: (a) a two-fold reduction in tissue hydration and a significant reduction of the diffusive motion of cellular water; (b) ten-fold decrease in cellular sodium; (c) six-fold decrease in tissue chloride; (d) the concentrations of intracellular potassium, and of extracellular sodium, potassium and chloride were constant; and (e) the cellular potential changed by 55 mV. A review of the literature concerning the physical state of potassium and water is made. The theoretical explanations of these findings are evaluated in terms of the classical membrane theory and the association induction hypothesis. PMID- 2205911 TI - A three-dimensional study of the morphology and topography of pericytes in the microvascular bed of skeletal muscle. AB - Digested tissue specimens and corrosion casts of rat soleus and tibialis anterior muscles were employed for this Scanning Electron Microscopy (SEM) study. The shape, morphology, and position of pericytes were compared to corresponding imprints on the cast surfaces. Pericytes, observed in digested tissue specimens, showed a typical morphological pattern: a central body with two primary processes that run along the capillary in opposite directions. From these primary processes, secondary ones arise and often encircle the vessel almost completely. On the surface of corrosion casts, roundish imprints were found in the microvascular tree at the same level where digested tissue specimens showed the presence of pericyte bodies. Along and around the cast surface, shallow grooves reproduced the course of the primary and secondary processes. The peculiar tridimensional arrangement of pericytes at the level of capillary bifurcations underlines their role in red cell flow regulation. However, if the mechanical linkage of the pericytes to the endothelium and their contractability is taken into account, additional roles of these perivascular cells may be hypothesized. PMID- 2205912 TI - [Proto-oncogene and cardiovascular diseases]. PMID- 2205913 TI - [Epidermal growth receptors]. PMID- 2205914 TI - [Cardiovascular estrogen receptors]. PMID- 2205915 TI - [Role of the liver in the metabolism of lipoproteins]. PMID- 2205916 TI - [Preganglionic vagal cardio-motor neurons]. PMID- 2205917 TI - [New pharmaceutical action of indomethacin]. PMID- 2205918 TI - Trace metal lung disease: in vitro interaction of hard metals with human lung and plasma components. AB - Hard metal pneumoconiosis is an occupational pulmonary disease caused by long term exposure to dust produced in the hard metal industry. In vitro experiments have been carried out to study the solubility and metabolic behaviour in human lung tissue and plasma of hard metal alloy constituents such as cobalt, tungsten, tantalum, titanium and niobium. The experiments were carried out using 60Co, 187W, 182Ta, 44Ti and 95Nb radiotracers in combination with neutron activation, radio-release tests and gel filtration techniques. Leaching experiments from neutron-irradiated hard metal dust showed that cobalt was highly soluble, especially in the lung cytosol and plasma, in comparison with tantalum and tungsten. The gel filtration experiments showed three biochemical pools of cobalt in both lung and plasma components, in accordance with the hypothesis that cobalt represents the allergic factor in the development of hard metal disease. High affinity for proteins was observed for Nb, Ta and Ti, but not for W, in agreement with the dissimilar biological half-lives of these elements in the body. The different ability of the metals to interact with biochemical components and to be solubilized in biological media may explain the various degrees of retention in the lung, which would influence the metabolic pathways. This would explain the presence of Co, Ta and W in body fluids, as well as in the public hair and toenails of hard metal workers. PMID- 2205919 TI - No excess of homozygosity at loci used for DNA fingerprinting. AB - Variable number of tandem repeat (VNTR) loci are extremely valuable for the forensic technique known as DNA fingerprinting because of their hypervariability. Nevertheless, the use of these loci in forensics has been controversial. One criticism of DNA fingerprinting is that the VNTR loci used for the "fingerprints" violate the assumption of Hardy-Weinberg equilibrium (H-W), making it difficult to calculate the probability of observing a genotype in the population. If one can assume H-W, the probability of observing the pair of alleles constituting an individual's genotype can be calculated by taking the product of the alleles' frequencies in the population and multiplying by two if the alleles are different. The evidence cited against assuming H-W is homozygote excess, which is presumed to be caused by an undetected mixture of two or more populations with limited interpopulational mating and distinct allele frequencies. For most VNTR loci, measurement error makes it impossible to test these claims by standard methods. The Lifecodes database of three VNTR loci used for forensics was used to show that the claimed excess of homozygotes is not necessarily real because many heterozygotes with similar allele sizes are misclassified as homozygotes. A simple test of H-W that takes such misclassifications into account was developed to test for an overall excess or dearth of heterozygotes in the sample (the complement of homozygote dearth or excess). The application of this test to the Lifecodes database revealed that there was no consistent evidence of violation of H-W for the Caucasian, black, or Hispanic populations. PMID- 2205920 TI - Acceleration of diabetes in young NOD mice with a CD4+ islet-specific T cell clone. AB - Nonobese diabetic (NOD) mice develop an autoimmune form of diabetes, becoming hyperglycemic after 3 months of age. This process was accelerated by injecting young NOD mice with CD4+ islet-specific T cell clones derived from NOD mice. Overt diabetes developed in 10 of 19 experimental animals by 7 weeks of age, with the remaining mice showing marked signs of the disease in progress. Control mice did not become diabetic and had no significant pancreatic infiltration. This work demonstrates that a CD4 T cell clone is sufficient to initiate the disease process in the diabetes-prone NOD mouse. PMID- 2205921 TI - The contralateral breast in ipsilateral breast carcinoma. AB - I examine the problem of the management of the opposite breast of a patient with ipsilateral carcinoma, reviewing the literature from the standpoint of the incidence of carcinoma in the contralateral breast, autopsy studies, blind biopsy results, and other factors such as age and multicentricity. In my series of 343 cases of carcinoma of the breast, there were 110 cases (32%) of bilateral mastectomy; 47 (43%) showed carcinoma in only one breast, 40 (36%) exhibited contralateral carcinoma, and 23 (21%) showed Consensus Added Risk Factors (CARF). The remaining 233 cases of carcinoma of the breast were treated by unilateral mastectomy. In 59 of these cases of bilateral mastectomy in which a prophylactic contralateral mastectomy had been performed, 15% showed carcinoma of the opposite breast and 22% showed CARF. In 51 cases, the contralateral mastectomy had been performed for clinical or radiographic indications. Of this group, 61% showed carcinoma and 20% showed CARF. All of my studies are based on routine pathologic studies and not on any specialized, subserial whole organ studies. PMID- 2205922 TI - Massive transfusion: complications and their management. AB - Massive transfusion, or the rapid administration of a quantity of blood products that approximates an individual's blood volume, is associated with many potentially lethal complications. If the need for transfusion is immediate, ie, before adequate typing and crossmatching procedures can be completed, O negative RBCs can be given safely in the interim. Hypothermia caused by cold banked blood is aggravated by multiple environmental factors and should be aggressively avoided through the use of heat lamps, warming coils, blankets, and other warming devices. The coagulopathy seen in massive transfusion probably has a mixed etiology involving dilution and consumption of clotting factors and platelets. Although fresh frozen plasma and platelets both play a critical role in blood replacement, deficiencies should be treated with appropriate component therapy dictated by coagulation studies rather than by protocol. Transfusion reactions, the most serious type of which is the hemolytic reaction, may go unrecognized in the bleeding patient in critical condition. Hemolytic reactions can usually be prevented by careful attention to administrative and clerical accuracy. Although the overwhelming majority of the 10 million units of blood transfused annually are uncontaminated, transmission of hepatitis and the human immunodeficiency virus through blood products remains a significant screening problem. Posttransfusion hyperkalemia and acidosis are more likely to be related to inadequate resuscitation from shock than to administration of blood. Citrate toxicity and hypocalcemia are usually self-limiting disturbances. Prophylactic use of calcium chloride is dangerous and unnecessary. The complexity of the conditions necessitating massive transfusion demands frequent reevaluation of multiple laboratory and clinical factors for effective resuscitation and for safe administration of blood. PMID- 2205923 TI - Culture in clinical medicine. PMID- 2205924 TI - Cunninghamella bertholletiae: an unusual agent of zygomycosis. AB - Cunninghamella bertholletiae shares many of the features typical of the other agents causing zygomycoses. Those who are immunocompromised constitute the major patient population at risk; the agents as a group are aggressive, the disease is often disseminated, and the pathologic picture of vascular invasion and tissue infarction is common. Unlike other agents of zygomycoses, Cunninghamella bertholletiae infection remains difficult to treat successfully even after early diagnosis and appropriate therapy. PMID- 2205925 TI - Pyomyositis and human immunodeficiency virus infection. AB - Pyomyositis is a bacterial infection of skeletal muscle usually caused by Staphylococcus aureus and characterized by localized muscle pain, swelling, and tenderness. The disease is endemic in the tropics. Though only approximately 50 cases have been reported from the continental United States, pyomyositis has been increasingly recognized here in the last decade. We report two patients with human immunodeficiency virus (HIV) infection and pyomyositis, and review five previously reported cases. Given the predisposition of patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) for infections caused by S aureus, pyomyositis may become increasingly more common in temperate areas. PMID- 2205926 TI - In vitro sensitivity of multiresistant Plasmodium falciparum to new candidate antimalarial drugs in western Thailand. AB - The present study, carried out in 1987 in Thailand, has been designed to validate the in vitro microtest system, standardized by the World Health Organization (WHO), for the new antimalarials pyronaridine and halofantrine. The sensitivity of naturally acquired, multiresistant populations of Plasmodium falciparum has been assessed in order to develop a data base for further longitudinal investigations. For both drugs the in vitro microtest system seems to be suitable. The concentration range of plates can be considered as almost ideal for pyronaridine (0.1-6.40 mumol/l) while for halofantrine (0.002-0.128 mumol/l) an upward extension of the concentration range would be appropriate. Validation studies with artemisinin demonstrated the need for revising the protocol for the production of the dosing solutions. In the light of current knowledge about therapeutic concentration levels it would probably be appropriate to adopt a range of 0.2-12.8 mumol/l. All tested isolates, except possibly three, showed sensitive responses to pyronaridine. The high EC99 value of halofantrine could be indicative of some resistance to this drug. Rank correlation analysis suggested cross-resistance of pyronaridine and chloroquine which could be of consequence for the future introduction of pyronaridine. PMID- 2205927 TI - New developments in malaria diagnostic techniques. PMID- 2205929 TI - Unilateral spondylolysis associated with spina bifida occulta and nerve root compression. AB - Three patients with unilateral spondylolysis and spina bifida occulta were treated with hemilaminectomy, pseudarthrosis excision, and bilateral posterolateral fusion. All patients had persistent radiating leg pain, a positive sciatic tension sign, an objective neurologic deficit, and neuroradiographic studies that confirmed isolated L5 nerve root entrapment at the pars defect. Postoperatively, all patients noted complete relief of their radicular symptoms. PMID- 2205928 TI - Immunofluorescence, enzyme-linked immunosorbent assay, particle agglutination and western blot for the detection of antibody to human immunodeficiency virus type 1. AB - Immunofluorescence assay (IFA) has been applied for detection of antibody to human immunodeficiency virus type 1 (HIV-1). To compare the IFA with an enzyme linked immunosorbent assay (ELISA) and particle agglutination (PA), we examined the antibody response to HIV-1 in 475 sera from AIDS, PGL and ARC patients as well as several risk groups and healthy persons by three methods. The positive results by any methods were confirmed by western blot (WB). The results by all methods were well correlated on the sera from 45 asymptomatic male homosexuals and 70 female prostitutes. There were some false positive results by ELISA in the sera from prisoners and healthy persons. Four sera from drug abusers were positive only by PA and IFA and were negative by ELISA. All were WB-inconclusive. Particle agglutination and IFA results were compared with western blot analysis on 208 ELISA-positive sera. All IFA-strongly positive sera (84%) were positive by western blot. The sera with weakly positive, negative and inconclusive results by IFA (16%) were possibly any of positive, inconclusive or negative by western blot. By PA, 200 of 208 (97%) sera were PA-positive and 1% of these sera were WB inconclusive while the PA-negative sera were either negative or inconclusive by western blot. These results suggested that PA is a simple and sensitive method for screening of HIV-1 antibody while IFA could be a primary confirmatory test and western blot would then be used for confirming any IFA-negative or inconclusive results. PMID- 2205930 TI - Atlanto-axial dislocation in association with rheumatic fever. A case report. PMID- 2205931 TI - Osteochondroma with cervical cord compression in hereditary multiple exostoses. PMID- 2205932 TI - Solitary bone cyst of a lumbar vertebra. A case report and review of literature. PMID- 2205933 TI - Odontoid fracture complicating ankylosing spondylitis. A case report and review of the literature. AB - The first reported case of odontoid fracture in ankylosing spondylitis is presented with a review of the literature. Conservative management with halo-vest immobilization may be a reasonable approach in the patient with ankylosing spondylitis who poses a high surgical risk. PMID- 2205934 TI - Anterior sacral meningocele. Case report and review of the literature. PMID- 2205935 TI - Ontogeny of the mucosal immune response. PMID- 2205936 TI - Structural specializations for antigen uptake and processing in the digestive tract. PMID- 2205937 TI - Lymphocyte homing into the gut. PMID- 2205939 TI - Mast cells. PMID- 2205938 TI - Human intraepithelial lymphocytes. PMID- 2205940 TI - Gastritis. PMID- 2205941 TI - The immunology of coeliac disease. PMID- 2205942 TI - Tropical sprue. PMID- 2205943 TI - Immunoproliferative small intestinal disease (IPSID): relationships with alpha chain disease and "Mediterranean" lymphomas. PMID- 2205946 TI - Corticosteroids and osteoporosis. PMID- 2205944 TI - The immunology of inflammatory bowel disease. PMID- 2205945 TI - Graft-versus-host disease of the intestine. PMID- 2205947 TI - Effect of caffeine on histamine bronchoprovocation in asthma. AB - It was recently reported that caffeine may reduce the clinical symptoms of asthma and may prevent the clinical manifestations of this disease. The effect of caffeine on histamine responsiveness is unknown. The effect of caffeine (5 mg/kg) and placebo on histamine responsiveness (the provocation concentration causing a 20% fall in FEV1, PC20) was studied in 10 subjects with mild asthma (prechallenge FEV1 84% of predicted value). The PC20 for histamine bronchoprovocation after caffeine ingestion was 2.65 (95% confidence limits 0.99, 7.10) mg/ml. After placebo the PC20 was 1.89 (0.96, 3.71) mg/ml. It is concluded that caffeine in a dose equivalent to about three cups of coffee has a very small effect, if any, on histamine bronchoprovocation in those with mild asthma. Specific instructions about not having drinks containing caffeine before histamine challenge are therefore not necessary. PMID- 2205949 TI - The use of a commercial ELISA for assay of thrombin-antithrombin complexes in purified systems. AB - Inhibition of thrombin by antithrombin III (AT) results in the formation of stable thrombin-AT complexes (TAT). An enzyme-linked immunosorbent assay (ELISA) following the sandwich principle is available for the determination of TAT complexes in human plasma, however, this ELISA method could not be used in purified systems containing thrombin and AT. It has therefore been modified for use in purified systems and an excellent correlation was found between the disappearance of thrombin and AT and the recovery of TAT complexes. Addition of thrombin inhibitor hirudin and heparin inhibitor polybrene into the reacting thrombin-AT mixture did not interfere with the assay of TAT. It was found that the use of siliconised tubes was necessary for the conservation of the TAT complexes. PMID- 2205950 TI - Proteolytic and immunologic comparison of human and bovine von Willebrand factor. AB - The structures of bovine and human vWF were compared by proteolysis with Staphylococcus aureus V8 protease and rattlesnake venom Protease I. Fragments were analyzed for chain composition, heparin binding, collagen binding, platelet agglutinating activity and recognition by a panel of monoclonal antibodies which reacted with both bovine and human vWF. Similar large fragments from the C terminal domain of vWF were seen in each case. The N-terminal domain resulting from cleavage of bovine vWF was much smaller than that seen upon digestion of human vWF with V8 protease. Protease I destroyed the heparin binding domain in human vWF. Bovine vWF was much less sensitive to proteolysis than was human vWF. PMID- 2205951 TI - Isolation of a hemorrhagic toxin from Mojave rattlesnake (Crotalus scutulatus scutulatus) venom. AB - A hemorrhagic toxin was isolated from Mojave rattlesnake venom. The isoelectric point of the toxin was 4.7 and its mol. wt was 27,000. Concentrations as low as 2 micrograms injected s.c. in mice caused hemorrhage greater than 5 mm in diameter. The toxin was fibrinogenolytic and hydrolyzed hide powder azure, casein and collagen. The toxin also partially inactivated complement. It had no activity against elastin, fibrin, and the chromogenic substrates S-2805, S-2302 and S 2238. Its esterolytic activity was 3% of the activity of the unfractionated venom. The enzymatic and hemorrhagic activities were inhibited by EDTA. The hemorrhagic toxin was absent or in low quantities in Mojave rattlesnake venoms containing Mojave toxin. Chromatography by HPLC easily distinguishes Mojave rattlesnake venoms into two types by the presence or absence of the hemorrhagic toxin. PMID- 2205948 TI - Relation of intraperitoneal and intravascular coagulation and fibrinolysis related antigens in peritoneal dialysis. AB - Patients received 2,000 ml of dialysate intraperitoneally with five exchanges per day during continuous peritoneal dialysis (CAPD) for the treatment of terminal renal insufficiency. During a dwell time of 4 h the dialysate reached a total protein concentration up to 100 mg/dl by mass transfer of intravascular proteins. The composition is dependent on the molecular weight of the proteins. This results in an intraperitoneal hemostatic system of low concentration and different composition. We found an intraperitoneal fibrinogen cleavage and thrombin-antithrombin III-complex formation leading to increased levels of fibrinopeptide A (FPA: 33.3 +/- 7.0 ng/ml) and thrombin-antithrombin III-complex (TAT: 4.7 +/- 0.4 ng/ml) in plasma by mass transfer from dialysate to plasma. t PA (tissue plasminogen activator) and PAI-1 (plasminogen activator inhibitor type 1) concentrations in plasma were within the normal range. The dialysate concentrations indicated a low local secretion. The fibrinolytic fibrin fragment D-dimer and the fibrinogen degradation product concentrations in plasma were greater than in dialysate. But the relations of the proteins between plasma and dialysate refer to a local intraperitoneal production as well. The results show that intraperitoneal coagulation predominates over fibrinolysis which is accompanied by an intravascular fibrinolysis in patients undergoing CAPD. Neoantigens produced in dialysate and diffused to plasma are comparable to changes seen in disseminated intravascular coagulation. PMID- 2205952 TI - Cleavage of immunoglobulins by moojeni protease A, from the venom of Bothrops moojeni. AB - Moojeni protease A, a proteolytic enzyme isolated from the venom of Bothrops moojeni hydrolyzes human and rabbit IgGs. The resulted fragments retained the combining though not the precipitating power or the property to fix complement. Similar to papain, moojeni protease A releases directly Fab fragments from IgG. In contrast to papain, however, the enzyme does not require the presence of thiol compounds either for activation or for reduction of the disulphide inter-heavy chain bridges. On the contrary, moojeni protease A is a metalloenzyme inhibited in the presence of thiol compounds. PMID- 2205953 TI - Mechanisms of transfusion-induced immunosuppression. PMID- 2205954 TI - Protection of islets of Langerhans from interleukin-1 toxicity by artificial membranes. AB - Recently it has been reported that interleukin 1 may play a central role in the immune destruction of islets. Since the mass weight of interleukin-1 is close to that of insulin, destruction of transplanted islets may be possible although they are enclosed in membranes that prevent penetration by immune-competent cells and cyto-toxic antibodies. The present in vitro study showed that the encapsulated rat islets are protected from high doses of IL-1 (1000 ng) inside a hollow fiber membrane with a cutoff of 50,000 D. The function of islets in a free-floating culture, however, was suppressed in a dose-dependent manner (1000 ng/L; 20-30% of controls). Histologically, no damage of the free-floating or encapsulated islets was observed at 1000 ng of IL-1-containing medium. Islets washed out of the devices after 2 days of exposure to IL-1 showed no difference in glucose stimulated insulin release when compared with islets not exposed that were kept in free-floating culture. It is suggested that an unspecific coating of the membranes by serum proteins (containing physiological IL-1 antagonists) may cause the protective effect. PMID- 2205955 TI - An unexpected effect of matching for HLA-A9 in renal transplantation. AB - The observation of elevated levels of HLA class I molecules in sera of HLA-A9 positive individuals, and their potential role in the regulation of the immune response, motivated us to study the effect of the presence of HLA-A9 in either kidney donor or recipient on graft survival. Analysis of data from unrelated first transplants performed within the Eurotransplant area revealed that in the group of patients who were not treated with cyclosporine (n = 2051), transplants with no HLA-DR mismatches in which donors (D) and recipients (R) shared the HLA A9 antigen (D+R+), had significantly poorer graft survival (P = 0.0001) than all other combinations, reaching a 20% difference at 5 years posttransplantation. This effect, which was not found in the CsA-treated patient group (n = 7297), was specific for HLA-A9. The implications of this findings are discussed in relation to the mechanisms of the alloimmune response. PMID- 2205956 TI - Effect of protein A immunoadsorption on panel lymphocyte reactivity in hyperimmunized patients awaiting a kidney graft. AB - Six hyperimmunized patients awaiting a kidney graft underwent immunoadsorption of separated plasma through a protein-A column to remove HLA antibodies. This procedure was partially limited by constant and rapid antibody resynthesis in spite of strong immunosuppression with cyclophosphamide and prednisolone. Only two patients could be grafted with previously positive--currently negative crossmatches. The first died of infection on day 40, having developed early chronic vascular rejection and the other returned to hemodialysis on day 285 after the development of transplant glomerulopathy. However, immunoadsorption seems to be effective in removing HLA antibodies having a titer below 1/2. Such extremely hyperimmunized patients should probably be excluded from the immunoadsorption program. PMID- 2205957 TI - Evaluation of amphotericin B-cyclosporine interaction in the rat. AB - Although a significant interaction between cyclosporine and amphotericin-B (AmpB) has been observed clinically, these findings have not been duplicated in animal studies. A total of 64 male albino rats were used in single- and multiple-dose experiments with AmpB and CsA in the absence or presence of systemic Candida infection. No significant differences in glomerular filtration rate were found in rats given single i.v. doses of AmpB 1 mg/kg compared with AmpB and CsA. Furthermore, rats given i.p. AmpB 1 mg/kg and CsA 10 mg/kg daily for 10 days showed no significant differences in GFR compared with animals given CsA alone. Morphology and CsA whole-blood pharmacokinetics were not different between groups administered single-dose CsA, AmpB, or the combination; similarities also existed with multiple-dose studies. In an attempt to mimic the clinical setting, 2 groups of rats were administered i.p. CsA 10 mg/kg/day for 10 days followed by inoculation of Candida albicans. After 48 hr, a single i.v. dose of AmpB 1.0 mg/kg was associated with a 33% decline in GFR compared with those given sterile water (P less than 0.05). Systemic clearance of CsA was markedly reduced in candidiasis rats administered AmpB compared with controls given sterile water. A significant reduction in renal Candida colony-forming units was found in rats given CsA and AmpB compared with those administered CsA alone. These data suggest that the presence of systemic Candida highlights the interaction of CsA and AmpB in the rat model. PMID- 2205958 TI - [Breast milk substitutes based on cow milk]. AB - "Adapted" or "humanized" breast-milk substitutes based on cows' milk are manufactured according to directives from a publication issued by the Ministry of Agriculture. The accepted recommendations for the daily intake (RDA) of nutrients is adjusted to the neonates' relatively low tolerance and provides a certain margin of safety in case of illness and slight inaccuracies in preparation. The recommendations are, however, often based on animal experiments, studies of pathological conditions etc. because the needs of the neonate are not known. There is a fundamental difference between RDA for chemical energy and various nutrients as the energy requirement is stated on the basis of average values while the requirements for specific nutrients are gives as upper and lower limiting values. In addition to nutrients, a long series of hormones, enzymes and antimicrobial factors are transferred to the infant via breast-milk. The nutritional significance of these is entirely or partially unknown. It is thus impossible to give the bottle-fed infant a diet which is quantitatively and qualitatively identical with that of a breastfed baby. Nevertheless, experience has shown that bottle-feeding usually proceeds satisfactorily. Galactosaemia and certain forms of medication in the mother constitute absolute contraindications to breast-feeding while phenylketonuria, certain maternal infections are relative contraindications to breast-feeding. Mothers should be prepared for breast feeding already during pregnancy but in the cases where the mother cannot, should not or does not wish to breast-feed, it is important to counteract any feelings of guilt, neglect or incompetence and, on the other hand, give her thorough training in artificial feeding of the infant. PMID- 2205959 TI - [The hyper IgE syndrome. Job's syndrome]. AB - Since 1972, 150 cases of the hyper-IgE-syndrome have been reported. The clinical manifestations are rather homogeneous with recurrent subcutaneous infections and infections in the respiratory tract, mostly with juvenile onset. Laboratory tests show minor eosinophilia and elevated immunoglobulin E-levels are always seen, partly specific to Staphylococcus aureus. Also varying decreases of polymorphonuclear leucocyte-chemotactic response are seen. There is no specific treatment of the disorder, only treatment of current infections has proved valuable. A case history is presented. PMID- 2205960 TI - [Purulent arthritis]. AB - At all ages, Staphylococcus aureus is the most common microorganism responsible for septic arthritis, but in children below five years of age Haemophilus influenzae is frequently found. In about 1/3 of the cases cultures are negative, primarily because of initiation of antibiotic therapy prior to sampling. A distended joint should be treated as infection until otherwise proved. Today repeated aspirations of the infected joint are recommended as initial treatment, if possible with additional joint lavage, together with systemic antibiotic therapy. In case with no clinical response within 2-4 days, surgical debridement of the joint with synovectomy is of utmost importance. Exercises without weight bearing are initiated at an early stage and weight-bearing avoided for six weeks. PMID- 2205961 TI - [Zinc therapy of tinnitus. A placebo-controlled study]. AB - Forty-eight patients with tinnitus of various etiologies underwent a placebo controlled, randomized, double-blind trial to assess whether treatment with zinc had any favourable effect on tinnitus. The trial tablets contained either 100 mg zinc sulphate as a depot tablet = 22 mg Zn++ (Zinclet) or placebo. The patients took tablets thrice daily for eight weeks. They indicated the severity of the tinnitus once weekly on a table graduated from 0 to 10. Serum zinc and serum albumin were measured before and after treatment. Out of the 48 patients with tinnitus, only one had hypozincaemia. During treatment, the serum zinc rose significantly in the group treated with zinc. No favourable effect of zinc treatment on tinnitus could be demonstrated. The fact that the serum zinc levels of the patients were within the normal range was probably an important reason for this. PMID- 2205962 TI - [The importance of early exercise therapy in the treatment of Colles' fracture. A clinically controlled study]. AB - Forty patients participated in a study of the importance of early occupational therapy for the prognosis in stable Colles' fractures. Seventeen patients were treated by an occupational therapist 1-3 days after the injury, and the need for appliances and home-care was estimated. Twenty-three patients completed the usual treatment. Five weeks after the injury, we found significantly (p less than 0.05) better function of the hand in the 17 patients with early occupational therapy. This difference in function could not be found after 13 weeks. The rate of complications was the same in the two groups. The results indicate that contact with the occupational therapist shortly after the injury is valuable in patients with stable Colles' fractures. PMID- 2205964 TI - [Naltrexone. An opioid antagonist to support the drug-free state in previous opioid addicts having stopped the habit]. AB - Naltrexon (Nemexin) is an opioid antagonist for oral use and with a relatively long duration time. The preparation is valuable as supplementary therapy for maintenance of the drug-free state in previous opioid addicts who have broken the habit. Clinical use requires thus that the patient is completely detoxified from opioids. Prior to commencement of the first dose of naltrexon, a drug-free period of seven to ten days is recommended. The drug-free state may be verified by screening of the urine or a trial injection of naloxon. The detoxification/drug free phase may be abbreviated by combined treatment with clonidine and naltrexon. Following the detoxification and drug-free phase, naltrexon therapy is initiated with the half dose (25 mg) on the first day and continued with 50 mg daily. The preparation should not be given to pregnant women or women who are breast feeding, to children under the age of 18 years or to patients with renal failure. Liver enzyme control tests should be carried out before and during treatment. The number of side-effects reported are few. In clinical investigations, naltrexon has proved to be valuable in a significant minority of opioid dependent patients investigated. Utility is increased with the patients' motivation for this form of treatment. The success rate for naltrexon supportive treatment measured by retention in the therapeutic programme is higher than for traditional drug-free treatment but lower than for methadone supported treatment. Effects on the risk of relapse in the long run have not been documented. PMID- 2205963 TI - [Defence mechanisms of the gastroduodenal mucosa. The significance of epithelial and subepithelial factors for the development of acute and chronic ulceration]. AB - Extra-epithelial, epithelial and sub-epithelial defence mechanisms protect the gastroduodenal mucosa against acid and pepsin. The epithelial mechanisms include epidermal growth factor, surface active phospholipids on the luminal membrane of the epithelial cells, sulfhydryl compounds and rapid epithelial restitution after damage. The sub-epithelial mechanisms include mucosal blood flow supplying the mucosa with bicarbonate needed for neutralization of the acid which penetrates the epithelium and the protective effect of the process of acid secretion. Prostaglandins, which partially protect the gastroduodenal mucosa against damaging agents, stimulate several of the abovementioned defensive factors but the precise mechanism of the action of prostaglandins is still unknown. The results of several experiments support the idea of the defensive factors being of importance in the development of acute and chronic gastroduodenal ulceration. At present, the therapeutic possibilities seem to be restricted and nothing indicates that stimulation of the defensive factors, only, is more effective in the treatment of peptic ulcer than inhibition of aggressive factors as acid and pepsin. PMID- 2205965 TI - [Observer variations in computerized 201 thallium myocardial scintigraphy]. AB - The observer variation (reproducibility) in computerized 201Tl scintigraphy was determined by describing the results of 20 investigations as being normal, suggestive of ischaemia or representing scar tissue. At an interval of two months, two physicians evaluated the results independently. As to normality, the interobserver variation was small, the level of agreement corrected for chance agreement, the kappa coefficient, being from 69-100%. For the diagnosis of ischaemia, kappa was also high, 58-100%. The intraobserver variations were of the same magnitude. In scar tissue, the kappa coefficients were somewhat lower. The present method has an acceptable observer variation in distinguishing between a diseased and a normal myocardium. The lower kappa coefficients for scar tissue and recent findings showing that persistent defects on the delayed images are viable tissue in 30% of the cases, makes it difficult to diagnose scar tissue. PMID- 2205966 TI - Avian Paramyxoviridae--recent developments. AB - This paper reviews the recent developments related to members of the Paramyxoviridae family which infect avian species. These developments include: (1) The identification of the virus responsible for the diseases turkey rhinotracheitis and swollen head syndrome in chickens as a member of the Pneumovirus genus, the first of this type to be isolated from birds. (2) The use of monoclonal antibodies prepared against Newcastle disease virus (NDV) and other avian paramyxoviruses which has enabled more exact and rapid diagnosis and greater understanding of the epizootiology of these viruses. (3) The nucleotide sequencing of the genome of NDV and subsequent amino acid sequencing of the major virus proteins have resulted in greater understanding of the pathogenicity of this economically important virus. PMID- 2205967 TI - From rabies to rabies-related viruses. AB - Antigenic differences between rabies virus strains characterized with monoclonal antibodies presently define at least four serotypes within the Lyssavirus genus of the Rhabdoviridae family: classical rabies virus strains (serotype 1), Lagos bat virus (serotype 2), Mokola virus (serotype 3) and Duvenhage virus (serotype 4). The wide distribution of rabies-related virus strains (serotypes 2, 3 and 4) and above all, the weak protection conferred by rabies vaccines against some of them (principally Mokola virus) necessitates the development of new specific vaccines. We first determined the complete nucleotide sequence of a rabies virus strain of serotype 1 (Pasteur virus) and characterized the structure of the viral genes and their regulatory sequences. We then extended this study to the Mokola virus genome. Five non-overlapping open reading frames were found in both viruses and had similar sizes and positions in both. Similarities were also found in the mRNA start and stop sequences and at the genomic extremities. Comparison of both genomes helps to analyze the basis of the particular antigenicity of these two serotypes. The sequence homology in the region coding for the viral glycoprotein was only 58% between the two viruses, compared with 94% between different rabies virus strains within serotype 1. This comparison, extended to other unsegmented negative strand RNA viruses, gives new insight into the understanding of rhabdoviruses and paramyxoviruses. Furthermore, molecular cloning provides a rationale for the genetic engineering of a future vaccine. PMID- 2205968 TI - Morbillivirus group: genome organisation and proteins. AB - The Paramyxoviridae family is divided into three genera: Paramyxovirus, Pneumovirus and Morbillivirus. In the last group, there are four closely related viruses which are seriously pathogenic for man and animals, and usually cause acute diseases. At least two of them (measles and canine distemper viruses) can cause a persistent infection which leads to a chronic disease of the nervous system that, in the end, is fatal. For a long time, the biochemical analysis of morbilliviruses was hampered by the high susceptibility of some of their proteins to proteolysis. With cloning and sequencing technology, more data on the biology of those viruses are now available. PMID- 2205969 TI - Use of vaccinia rabies recombinant for oral vaccination of wildlife. AB - A vaccinia rabies recombinant virus was constructed and shown to induce the synthesis of rabies virus glycoprotein in infected cells and to induce rabies virus neutralizing antibodies and protection in susceptible animals. Active when orally administered, this recombinant is a good candidate for the development of vaccines for wild animal rabies vectors. This recombinant was found stable, safe for target and non-target animal species, and protective for most of the rabies vectors. After extensive experimental studies conducted under controlled conditions, it as used in limited field trials and in an extensive open field trial. The preliminary results confirmed its basic properties and potential for rabies eradication. PMID- 2205970 TI - Contribution of molecular biology to the study of the porcine interferon system. AB - We have performed molecular studies on the pig interferon (IFN) system (i) to analyse the role played by endogenous IFN in neonatal viral enteritis such as transmissible gastroenteritis and possibly to obtain, via recombinant DNA technology, a new anti-infectious and immunomodulatory agent in this species, (ii) to characterize the structure and biological functions of the IFN-like antiviral activity produced by the porcine embryo at the time of implantation in the uterus. By probing porcine genomic libraries with human and porcine IFN-alpha probes to isolate related genes, we have shown that the porcine IFN-alpha multigene family included, like several other mammalian species, two subfamilies of related but distinct genes. Class I subfamily contains at least 11 loci, located on chromosome no. 1, among which nine have been cloned and two (potentially functional) sequenced. Class II subfamily, which is specifically expressed by the embryo of ruminants before implantation, contains at least seven loci among which six have been cloned. One of the sequenced class I loci: PoIFN alpha 1 encodes a 189 amino acids (AA) preprotein. After removal of the sequence encoding the putative signal peptide (23 N-terminal AA) this gene was inserted into an Escherichia coli bicistronic expression vector allowing intracellular synthesis of mature porcine IFN-alpha 1 (methionyl IFN-alpha 1). Expression of the recombinant protein was optimized by insertion of a seven base pairs long random synthetic sequence in the intercistronic region, followed by cloning in E. coli and immunodetection of clones expressing high amounts of recombinant protein. The E. coli strain obtained produced high levels of a 18,000 Da protein exhibiting the same in vitro overall biological properties as leucocyte derived porcine IFN (LeuIFN). However, it had a stronger antiviral effect on porcine cells than LeuIFN. After immunoaffinity purification to a specific activity of 5 10 x 10(7) International Units (IU)/mg of protein, pharmacokinetic and pharmacological studies were realized to determine the in vivo half life of this rIFN-alpha in the pig. These experiments revealed no major toxic effects in newborn (given 5 x 10(6) IU/kg) or adult (1 X 10(6) IU/kg) pigs. A significant pyrogenic effect (+ 1.5 degrees C) was noted only in the adults. PMID- 2205971 TI - Mass mortality in seals caused by a newly discovered morbillivirus. AB - During a recent disease outbreak among harbour seals (Phoca vitulina) in the North and Baltic seas, more than 17,000 animals have died. The clinical symptoms and pathological findings were similar to those of distemper in dogs. Based on a seroepizootiological study, using a canine distemper virus (CDV) neutralization assay, it was shown that CDV or a closely related morbillivirus (phocid distemper virus-PDV) was the primary cause of the disease. The virus was isolated in cell culture from the organs of dead seals and characterized as a morbillivirus by serology (immunofluorescence neutralization and enzyme-linked immunosorbent assays) and by negative contrast electron microscopy. Experimental infection of SPF dogs resulted in the development of mild clinical signs of distemper and CDV neutralizing antibodies. The disease was reproduced in seals by experimental inoculation of organ material from animals that had died during the outbreak. However, seals that had been vaccinated with experimental inactivated CDV vaccines were protected against this challenge. This fulfilled the last of Koch's postulates, confirming that the morbillivirus isolated from the seal organs, was the primary cause of the disease outbreak. The recent demonstration of the presence of a similar virus in Lake Baikal seals (Phoca sibirica), which infected these Siberian seals 1 year before the northwestern European seals were infected, raises new questions about the origin of this infectious disease in pinnipeds. PMID- 2205972 TI - Eradication of infectious bovine rhinotracheitis in Switzerland: review and prospects. AB - Ten years after the first outbreak of infectious bovine rhinotracheitis (IBR) in Swiss dairy cows, the national cattle herd is almost free from infection with IBR virus (bovine herpesvirus 1, BHV 1). The national programme for the eradication of IBR was divided into four phases: (1) Prevention of transmission of the infection by restrictions on trade of bovines and assessment of the prevalence of cattle with antibodies to BHV 1. (2) Slaughtering animals with antibodies to BHV 1 in order to eradicate BHV 1 from breeding herds. (3) Detection and eradication of further BHV 1 reservoirs (e.g. fattening cattle). (4) Monitoring programme and legal actions in order to maintain the favourable situation. Approximately 50,000 animals were slaughtered in the course of the eradication of IBR. The total costs amounted to approximately SFr. 110,000,000 over 10 years. The costs for maintaining the situation are estimated at approximately SFr. 5,000,000 per annum. PMID- 2205973 TI - The expression of the Autographa californica nuclear polyhedrosis virus genome in insect cells. AB - This report presents a synopsis of recently published work in our laboratory on the molecular biology of the insect baculovirus Autographa californica nuclear polyhedrosis virus (AcNPV). The following studies have been summarized. (1) On the mode of transcription of the AcNPV genome in insect cells. (2) Translation of proteins encoded in the 81.2 to 85.0 map unit segment of AcNPV. (3) Inserts of insect cell DNA in the AcNPV genome. (4) Expression of influenza (fowl plague) virus haemagglutinin in Spodoptera frugiperda insect cells, and successful immunization of chickens. (5) Synthesis of the influenza virus haemagglutinin in insect larvae by recombinant AcNPV. This insect virus system will continue to serve as a model for research on the molecular biology of insects. Moreover, the baculovirus system has been recognized as a very efficient and safe eukaryotic expression vector. PMID- 2205974 TI - Iscoms. AB - The common problem for defined purified antigens or antigen determinants has been to make them immunogenic regardless of whether they are produced conventionally, produced as cloned genetechnology products or chemically synthesized. The first problem is to get the protective antigen into a submicroscopic particle where the antigen is presented in several copies, i.e. as a multimer. For some antigens it seems also necessary to enhance the immunogenicity with an adjuvant. The immunostimulating complex (iscom) was created to fulfil these criteria by assembling antigens in a multimeric form on a matrix with built-in adjuvant to form a particle. The components are held together by hydrophobic interactions. The iscom has turned out to be highly immunogenic, inducing high antibody mediated and cell-mediated immunity including cytotoxic T cell response to influenza virus. In a mouse model iscoms containing influenza virus envelope proteins induced protective immunity by one intranasal administration. Protective immunity was also induced to a retrovirus--feline leukemia virus. In a monkey model system iscoms containing gp360 of Epstein-Barr virus induced protection to induction of tumours. Iscoms have also been used as carriers for small molecules such as oligopeptides, which combination appeared to be highly immunogenic. PMID- 2205976 TI - The radiation phosphene. AB - A low flux of X-rays below the Cerenkov energy threshold generates a phosphene by direct action on the retina without a fluorescence in the ocular media. X-rays above the Cerenkov threshold can generate only a faint luminescence in the lens and cornea. From experimental work on humans in 1905 with unencapsulated radium, it is known that approximately 80% of the intensity of the radium phosphene is from the beta-ray component and approximately 20% from the gamma-ray. From calculations of the photon yield due to Cerenkov radiation in the eye from radium, one finds intensities of approximately 90% and approximately 10% for beta and gamma-rays, respectively, if only Cerenkov radiation is considered. Thus, one may conclude that the dominant mechanism of the radium phosphene is Cerenkov radiation, primarily from electrons and not fluorescence as previously speculated. The term "radium phosphene" is a misnomer and should be subsumed along with the X-ray phosphene and particle induced visual sensations under the name "radiation phosphene". PMID- 2205975 TI - Is TNF involved in the progression of AIDS? PMID- 2205977 TI - Development of visual sensitivity to light and color vision in human infants: a critical review. AB - The recent literature on test threshold and color vision in human infants is critically reviewed. Test thresholds are higher in infants than in adults at the absolute threshold and at all adapting luminances, but approach adult values rapidly over the first six months of life. The spectral luminous efficiency function of infants is similar to V(lambda) above 1.0 log phot. cd/m2. For lights below about 1.0 log scot. cd/m2 and wavelengths shorter than 590 nm, the luminous efficiency function is similar to V'(lambda). The luminous efficiency of any given stimulus may differ markedly between infants and adults, especially when the adult data depend on the temporal and spatial parameters of the stimuli. Color vision improves greatly over the first three postnatal months, and most normal 3-month olds have at least some color vision. The overall insensitivity of infants to contrast is likely to provide a satisfactory explanation of the poor color vision of infants. The critical immaturity primarily responsible for the high thresholds and poor color vision of infants is probably after the site of visual adaptation, although lower-level factors may also play a role. PMID- 2205978 TI - Fine needle aspiration biopsy in the diagnosis of breast cancer. AB - A prospective study of 176 Fine Needle Aspiration Biopsies (FNAB) in 172 patients was carried out to assess the accuracy of FNAB in diagnosing breast cancer at the University Hospital of the West Indies. The results showed 99 per cent and 97 per cent accuracy and sensitivity rates, respectively. There were no false positives and a one per cent false negative rate. FNAB provides a rapid, safe and cheap method of accurately diagnosing breast cancer. PMID- 2205980 TI - [Pathogenesis and clinical features of various forms of pulmonary emphysema in children]. AB - On the basis of the views of Lynne Reid 4 principal pathological mechanisms of pulmonary emphysema development are discussed. The clinical manifestations of the most frequent forms of emphysema characteristic of childhood are presented. PMID- 2205979 TI - [Prognostic factors in acute myocardial infarction]. AB - The key problem of modern cardiology is determination of prognostic factors in acute myocardial infraction which could make possible a proper assessment of the condition of the patients and outlining of guidelines for further therapeutic management. The newest reports on various parameters of prognostic significance in acute myocardial infraction and have a decisive importance of the further fates of the patients after completic of infarction necrosis, are discussed. PMID- 2205981 TI - [Pancreatic preparations--their use and standardization]. PMID- 2205982 TI - [Comparison of the treatment of obesity by surgical methods and gastric balloon]. AB - The paper is a review of the reports on the treatment of simple obesity, comparing the methods of surgical therapy used as yet with the new method of intragastric balloon. This method is simple, repeatable, connected with a low number of complications making possible a mean weight loss of 16 kg during one course of treatment. PMID- 2205983 TI - [Use of nociceptive flexion reflex in the studies of analgesia in in humans]. PMID- 2205984 TI - [Effect od external drainage of the biliary tract on bile infection]. AB - After a brief review of the pertinent literature the results are presented of bacteriological examinations carried out in patients with calculosis of the gallbladder and bile ducts. The study demonstrated that E. coli was the prevailing bacterium in the bile and that external drainage of the bile ducts exerts a direct effect on increased incidence of contamination of bile in bile ducts even despite antibiotic treatment. PMID- 2205985 TI - [Glucose-6-phosphate dehydrogenase as a marker of genetic predisposition to neoplasms]. AB - In the light of reports in the literature the data are presented on the importance of glucose-6-phosphate dehydrogenase in cell metabolism. The effect of decreased enzyme activity or its complete absence on the functions of the cell, and the clinical conditions associated with deficient enzyme activity are described. The influence is discussed of the genetic determination of the enzyme on the occurrence of phenotypic effects, and the use of the mosaicism phenomenon in the study on the pathogenesis of certain disturbances. Several reports from the literature are quoted concerning the study of the reverse relationship between a deficiency of the activity of the enzyme and the incidence of carcinoma. The necessity is stressed of including electrophoretic techniques into the studies. PMID- 2205986 TI - [Treatment of fetal hydrocephalus]. PMID- 2205987 TI - [The development of immunoscintigraphy into a routine method]. AB - Immunoscintigraphy (IS) along with nuclear magnetic resonance, is the most recent method in malignant tumour imaging. In the following, the development of IS is shown up from the very beginning to the routine standard of today. PMID- 2205989 TI - [Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: a prospective study]. PMID- 2205988 TI - Prospective study of the incidence of ultrasound-detected hepatic hematomas 2 and 24 hours after percutaneous liver biopsy. AB - Recently, a high incidence of hepatic hematomas following percutaneous liver biopsy was reported. This induced us to undertake this prospective ultrasound examination before, as well as 2 and 24 h after, percutaneous liver biopsy, using a Menghini needle (O 1.4 mm), in 93 patients for diagnostic purposes. Two hours after biopsy a small subcapsular fluid margin was found in one patient (1.1%) which disappeared within 24 h. We conclude that hepatic hematomas are not frequent following percutaneous liver biopsy and that it remains a safe diagnostic procedure to find out the reason for chronically elevated liver enzymes and evaluate suspected diffuse parenchymal lesions of the liver. PMID- 2205990 TI - [A case of pathomimesis]. AB - Pathomimesis (skin artefacts, Munchausen syndrome, artificial dermatitis, etc.) is an artificial deficiency of the skin and it is referred to a group of psychosomatic disorders, evidencing affective and in some cases paranoiac delirium disturbances. A case of this condition is described. PMID- 2205991 TI - [The immunologic situation of the placenta and its significance for disorders in early pregnancy]. AB - Reference is made in numerous recent immunological studies to immunological mechanisms which were found to play a role in acceptance of pregnancy or habitual abortions. The most important theories likely to offer explanations for these phenomena are reviewed in some detail, including hormonal immunosuppression, immunologic-anatomic barrier at the placenta as well as blocking factors and anti sperm antibodies. Molar pregnancy is associated with a particular immunological situation. None of the theories mentioned can be preferred, for the time being, to explain acceptance of normal pregnancy or the causes of recurrent spontaneous abortions. PMID- 2205992 TI - [Mutations of mitochondrial DNA and their relation to neuromuscular diseases]. AB - According to present knowledge, mutations of mitochondrial DNA (mtDNA), implicated in the mitochondrial theory of carcinogenesis that had been inaugurated 50 years ago by Graffi, appear to be involved in malignant transformation of cells, although no definite evidence has been provided, as yet. However, as very recently elucidated, a clear-cut association exists between different classes of mutations of mtDNA (among them point mutations, deletions and duplications) and some human mitochondriopathies, particularly neuromuscular diseases. These include Leber's hereditary optic neuropathy, the Kearns-Sayre syndrome and two encephalomyopathies known by the acronyms MERRF and MELAS syndrome. The different alterations of mtDNA, though variable, can be assigned to defined positions on the genetic map of mtDNA. Point mutations of mtDNA seem to occur preferentially in conjunction with maternally inherited disorders. Although the results obtained so far are of interest mainly in terms of cognitive theory they provide new stimuli for the development of molecular diagnosis, genetic counselling and possibly for more effective treatment of the above diseases. PMID- 2205993 TI - [The history of the Autopsy Department of the Berlin Charite hospital. 1. Founding of the Autopsy Department and Philipp Phoebus as the first prosector]. AB - The opening of the Prosector's Department at the Charite of Berlin and appointment of its first Prosector are reported in this paper. The scientific need for getting clinical postmortem investigations performed by full-fledged anatomists or for having them at least anatomically supervised and pressures resulting from Europe's first cholera outbreak, approaching Berlin about 1830, had been the principal motivations behind the initiative. On May 8, 1831, Dr. Philipp Phoebus was appointed the first Prosector of the Charite of Berlin. The position had been offered as a part-time job. Most aspects relating to the post had not been clearly defined by that date, for example, the rights and duties of a Prosector, his integration with the general pattern of Charite services, and his subordination to the local hospital committee. Phoebus made an unsuccessful attempt to define and thus secure the Prosector's position by means of a self drafted policy paper. Misunderstandings on end and strained relations with the clinicians on the spot prompted him to quit service after 16 months. An account is given of his short but successful time at Charite, with reference being also made of the specific reason for his resignation. An outline is subsequently presented of Phoebus' further life and work, including scientific careers in Berlin, Stolberg/Harz, and at Giessen University where he held a professorship in pharmacology. PMID- 2205994 TI - [The course of pregnancy following cerclage. 1. Singleton pregnancies]. AB - In a retrospective study about value of cerclage 160 patients with singleton pregnancies had been studied in two subgroups dependent from the moment of operative cervix closure and opposed a matched pair control group without cerclage. In both subgroups there is a more loaded obstetric history with reference to previous abortions. Preterm labour and premature rupture of membranes and tocolysis could be observed significantly more frequent in both subgroups than in the controls. Obstetric results are worse in the cerclage group with respect to birth weight, height and pregnancy duration, especially correlations between prognosis and opening of the womb at the moment of cerclage could be proved. Amniotic infection syndrome was three times more frequent in the cerclage group than in the controls. Contrary to the literature no increased frequency of cervical laceration or caesarean sections could be observed. In conclusion our results are contrary to the optimistic view on cerclage, important not only for indication, but also for instruction of patients before therapy. PMID- 2205995 TI - [Sacrococcygeal teratoma. Prenatal diagnosis and prognosis]. AB - The routine use of ultrasonics during pregnancy allows an early diagnosis of a sacrococcygeal teratoma (SCT) with a high degree of certainty. The perinatal management is shown in a four case example prenatally diagnosed. The assessment of N-Acetylcholinesterase in the amniotic fluid in cases of cystic teratomas does not allow a safe differentiation from a myelomeningocele. A puncture of the tumor can be helpful for the verification of the diagnosis. Cells of all three germ layers may be found in the cytological fluid. The sonomorphological differentiation into solid and cystic tumors may play a significant role for the intrauterine growth. Even when diagnosed very early, cystic tumors do not compromise the intrauterine growth. Large solid tumors may lead to hydrops fetalis and intrauterine death. Furthermore, the prognosis depends on concomitant malformation as well as on the intracorporal spreading of the tumor. Therefore, a careful ultrasonic examination allows a good prenatal prognosis as to the severity of the malformation. Delivery is done by caesarean section in cases of large cystic-solid tumors. Small teratomas as well as most cystic tumors allow vaginal delivery after having been punctured previously. PMID- 2205996 TI - [Development of the regional society in the Dresden and Cottbus area and its current scientific contribution]. PMID- 2205997 TI - Regional anesthesia preferable for Colles' fracture. Controlled comparison with local anesthesia. AB - In a prospective randomized study of 99 displaced Colles' fractures, regional intravenous block was compared with local anesthesia in the fracture hematoma. Patients treated with regional intravenous block had less pain during the manipulation of the fracture and better grip strength at the 6-month follow-up. The anatomic end result (dorsal angulation) was better after regional anesthesia. PMID- 2205998 TI - Prognosis of total hip replacement. A Swedish multicenter study of 4,664 revisions. PMID- 2205999 TI - Cardiovascular risk in young Finns. Experiences from the Finnish Multicentre Study regarding the prevention of coronary heart disease. AB - A large multicentre study of coronary heart disease risk factors and their determinants in children and adolescents was planned in the late 1970s. The main cross-sectional study with 3,596 subjects was made in 1980, and two follow-up studies have been carried out, in 1983 and 1986, respectively. In addition, a study with 630 newborns was carried out in 1981, and a series of children aged 1 to 36 months was collected in 1981-1982. Cord blood, serum cholesterol was about 1.5 mmol/l, which is no different from the level found in other studies. The diet of mothers had no effect on the cholesterol values of the newborns. The cholesterol level of infants and small children was correlated with the amount and quality of fat eaten. The dietary habits of the family were correlated with the family's standard of education, which calls for intervention measures already in early childhood. Serum cholesterol levels have decreased in Finnish children during the 1980s by about 1% per year, which should be reflected in coronary heart disease morbidity and mortality in the future. PMID- 2206000 TI - Immunity related to exposition and bacterial colonization of the infant. PMID- 2206001 TI - Immunologically mediated damage to the intestinal mucosa. AB - This review discusses experimental and clinical evidence for the existence of immunologically mediated damage to the intestinal mucosa. The discussion of mechanisms of gastrointestinal immunoregulation and lymphocyte recirculation via recently described homing receptors is preceded by a summary of the basic structures of the gut-associated lymphoid tissues (GALT). The relevance of food induced systemic hyporesponsiveness (oral tolerance) to the prevention of immunologically mediated damage to intestinal mucosa is discussed in the light of anaphylactic (Type I) and delayed type (Type IV) hypersensitivity reactions. Other, less well defined, mechanisms of allergic injury are also briefly discussed. It is postulated that the abrogation and/or modulation of orally induced tolerance is the pathogenetic mechanism underlying the induction of food sensitive enteropathies. PMID- 2206002 TI - Growth and development in children with thalassaemia major. PMID- 2206003 TI - Effects of short-term growth hormone therapy in short children without growth hormone deficiency. AB - Evaluation of 24-hour endogenous growth hormone (GH) secretion was carried out in 62 children, aged 7-16 years, who did not have classic GH deficiency (GHD). The mean 24-hour GH concentration, determined at 20-minute intervals over 24 hours, was variable, ranging from 1.28 to 11.39 micrograms/l with a mean of 4.95 +/- 2.55 micrograms/l (+/- SD). There was a positive correlation between mean 24-hour GH concentration and plasma insulin-like growth factor I (IGF-I) values (r = 0.54; p less than 0.01). Recombinant human GH, 0.1 IU/kg/day was administered to 30 of the 62 children for 6 months followed by 6 months' observation without treatment. Thereafter, GH was administered at the same dose for a further 6 months to 16 children. The mean height velocities before, during, and after the first treatment period were 4.3 +/- 0.9, 7.3 +/- 1.9 and 4.9 +/- 2.0 cm/year (mean +/- SD), respectively. The height velocity during treatment was greater than pre- and post-treatment values (p less than 0.001). The height velocity increased again during the second treatment period to a mean of 8.5 +/- 2.0 cm/year (p less than 0.001). Nine other children were treated continuously in a similar manner for 1 year and their height velocity increased significantly from 4.1 +/- 1.4 to 6.0 +/- 1.9 cm/year (p less than 0.001). According to our criteria, 29 of the 39 children (74.4%) who were treated for 6-12 months showed a GH-dependent height increase during therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206004 TI - Effects of growth hormone in short, slowly growing children without growth hormone deficiency. Australasian Paediatric Endocrine Group. AB - The aim of the study was to measure the real effect of growth hormone (GH) treatment compared to the effect of placebo, since a placebo effect has been shown in other studies involving interventional growth therapy. Changes in height velocity and insulin-like growth factor I (IGF-I), relative to pretreatment variables, were examined during a 12-month, double-blind study. PMID- 2206005 TI - Growth hormone treatment in non-growth hormone-deficient children: effects of stopping treatment. AB - Overnight physiological growth hormone (GH) secretion was evaluated in 95 short, prepubertal children (73 boys, 22 girls). All the children were below the 3rd centile for height and achieved GH levels greater than 15 mU/l following pharmacological stimulation. The mean average GH level was 7.1 mU/l and the mean sum of pulse amplitudes 80.4 mU/l. No relationship was found between age, height or height velocity and any of the parameters of GH secretion. The group was randomized to receive placebo, GH or remain under observation for the first 6 months and then all patients received GH treatment for a further 6 months. Those treated with GH, 0.27 IU/kg (0.1 mg/kg) three times weekly, in the first phase, demonstrated a mean increase in height velocity SDS of 3.24. There was no difference in growth response between the placebo or observation groups. In the second 6-month period, all children received GH according to the same dose regimen; they were then observed for a further 6 months following its discontinuation. In the 6 months following withdrawal of GH, all groups showed a significant fall in height velocity SDS, which returned to pretreatment levels, without demonstrating 'catch-down' growth. Repeat sampling of overnight GH secretion within 3 days of discontinuing GH showed normal secretory patterns with a small reduction in mean peak amplitude. These results suggest that short children without classic GH insufficiency respond well to exogenous GH in the short term and return to pretreatment height velocities afterwards. Consequently, it may be possible to increase final adult height in such children by GH treatment. PMID- 2206006 TI - High-dose growth hormone treatment of non-growth hormone-deficient children: preliminary results after 2 years. AB - The growth response to high-dose growth hormone (GH) therapy was investigated in 10 short, prepubertal, slowly-growing children. Two years treatment with recombinant human GH at a dose of 0.3 IU/kg daily 7 days per week resulted in a mean height increase of 19.5 cm (range 17-23 cm). There was a slight but not significant acceleration of bone age maturation. The treatment also induced a sustained increase in insulin secretion without detectable changes in glucose tolerance. PMID- 2206007 TI - Effects of 3 years of growth hormone therapy in short normal children. AB - The effect of 3 years of growth hormone (GH) treatment on growth rate, predicted height, carbohydrate and metabolic status, and thyroid function was studied in 16 short prepubertal children growing with a normal pretreatment growth rate. The height velocity SDS increased from a pretreatment value of -0.44 +/- 0.33 (mean +/- SD) to a value of +2.20 +/- 1.03 during the first year of treatment. It was maintained at a value above zero over the subsequent 2 years. By the end of the third year of treatment, the predicted final height had increased by 6.8 cm in the boys and by 4.2 cm in the girls (p less than 0.001 and p less than 0.01, respectively). Increasing the dose of GH on a body surface area basis reduced the deceleration of growth observed during the second year of treatment, leading to an improvement in height prognosis over that year. Glucose homoeostasis was achieved initially at the expense of an elevation in fasting serum insulin concentration, but this had returned to pretreatment values by the end of the second year of therapy. PMID- 2206008 TI - Growth hormone receptors--their structure, location and role. PMID- 2206009 TI - Regulation of the cell surface growth hormone receptor. PMID- 2206010 TI - Growth hormone regulation of gene expression. PMID- 2206011 TI - Growth and development of children with chronic renal failure. Study Group on Pubertal Development in Chronic Renal Failure. AB - Preliminary results from an ongoing multicentre study on pubertal growth and sexual maturation in chronic renal failure are presented. Puberty was delayed by approximately 2.5 years in both sexes in children with chronic renal failure. There was also an irreversible decline in height SDS during puberty. The pulsatile secretion of growth hormone (GH) and luteinizing hormone (LH) were disrupted in patients on conservative treatment or dialysis compared with those in patients with renal transplants; the mean nocturnal GH level and the mean GH peak amplitude were increased, while the number of pulses and peak amplitude of LH were decreased. The biopotency of LH, expressed as the ratio of bioactive to immunoreactive LH, was suppressed in patients with renal transplants. PMID- 2206012 TI - Growth and endocrine function in children receiving long-term steroid therapy for renal disease. PMID- 2206013 TI - Growth and development in chronic inflammatory bowel disease. PMID- 2206014 TI - [Combined action of pyronaridine and sulfadoxine/pyrimethamine against Plasmodium berghei ANKA strain in mice]. AB - Pyronaridine, a highly effective antimalarial drug, was synthesized and developed by this institute. In order to test whether the joint blood schizontocidal action of pyronaridine (PND) and 2:1 mixture of sulfadoxine/pyrimethamine (SP) resulted in a potentiation or an additive effect, groups of P berghei ANKA strain-infected mice were treated with various single oral doses of PND and SP. Thin blood smears were made after 72 h and the parasitemia-negative rates were calculated. The ED50 values obtained were plotted in isobolograms. An additive action of this triple combination was demonstrated. Mice were inoculated with P berghei ANKA strain infected erythrocytes 3 and 2 d after the mice were given a single oral dose of PND 10 mg/kg alone, or combined with SP 3 mg/kg. Thin blood smears made on d 3, 5, 8 and 10 revealed that the parasitemia-positive rates and the duration of residual blood schizontocidal action of PND used alone was similar to that of PND used in combination (P greater than 0.05). Three groups of mice carrying P berghei ANKA strain gametocytes were administered orally with pyrimethamine 0.1 mg/kg, SP 0.3 mg/kg and SP 0.3 mg/kg plus PND 0.5 mg/kg, respectively. Anopheles stephensi were then fed on the mice 2 h after the medication. There resulted no significant differences of gametocytocidal and sporontocidal effects among the 3 groups, since the oocyst-positive rate and the glandpositive rate were similar in these groups. PMID- 2206015 TI - A pilot study with monosialoganglioside GM1 on acute cerebral ischemia. AB - Reported here are the results of an open controlled study on the use of GM1 in cases of ischemic strokes in its acute phase. A statistically significant improvement was observed in cases treated with GM1 for neurological deficits (assessed by Mathew's rating scale, modified by Fritz-Werner) at 21, 60 and 120 days and for disability at 120 days. PMID- 2206016 TI - Statistical analysis of the clinical trial of a therapy for Alzheimer's disease. Univariate tests and logistic regression. AB - A placebo controlled, randomized, double blind, multicentric clinical trial was carried out in Italy to test the effectiveness of a drug in the therapy of Alzheimer's disease. Informed consensus was gained for the inclusion of 130 patients, whose mental performance was assessed before allocation and after 3, 6, 12 months of continuing assumption of treatment. 14 different outcome variables were used. The main analysis was performed on measures adjusted for baseline, using both univariate and multivariate techniques for each of the three assessing times. The former is mainly descriptive in its scope and allows an analytical view of the results; the latter protects from a too high type I error probability, without implying the loss of power produced by the Bonferroni correction. The techniques are respectively Mann-Whitney test, and analysis of deviance of logistic models, which was suggested by Cupples et al. (1984). In the latter we used the allocation of the patients as response variable, and compared the predictor containing all outcome measures with that having just a constant term. It is shown that a significant difference of fit implies that treatment significantly affects outcome. For the 3 and 6 month follow-up assessment, univariate tests do not show clearcut trends (only 1 outcome measure is significantly better for the drug, none is for the placebo). After 12 months, a trend shows: 13 out of 14 variables are in favour of the drug and 4 of them are significant. Of the three multivariate test carried out, that relative to the 12 month follow-up is significant at the 0.05 level, which is consistent with the univariate results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206017 TI - The role of echosonography in diagnosing IUD complications. AB - One hundred and one healthy women with intrauterine devices (IUDs) were studied by echosonography; 46 women had Multiload Cu375 IUD (group I), 30 Ginetik TCu220 IUD (group II) and 25 Lippes loop IUD (group III). In groups I and II echosonography was performed 30 minutes, 30 days and 3 and 6 months following insertion. Group III was investigated only when complications developed. Echosonography showed high accuracy in detecting IUD expulsion or incorrect position, and pregnancy in the IUD wearer. PMID- 2206018 TI - A comparative clinical trial of Norinyl 1 + 35 versus Norinyl 1 + 50 in Merida, Yucatan, Mexico. AB - A comparative clinical trial of two combined oral contraceptives differing only in estrogen type and dosage was conducted at the Centro de Investigaciones Hideyo Noguchi in Merida, Yucatan, Mexico. The trial was designed to determine the differences between Norinyl 1 + 50 (Syntex) and Norinyl 1 + 35 (Syntex) in rates of discontinuation and frequency of selected side-effects which might contribute to method discontinuation. Three hundred women were randomly assigned to either the Norinyl 1 + 35 group or to the Norinyl 1 + 50 group and follow-up visits were scheduled at 1, 4, 8 and 12 months after admission. In the Norinyl 1 + 35 group, more women experienced an increase in intermenstrual bleeding (primarily staining and spotting) (p less than 0.05), breast discomfort (p less than 0.05) and nausea than in the Norinyl 1 + 50 group. There was a significantly higher discontinuation rate for personal reasons, such as desired change of method and method not needed, among the women taking Norinyl 1 + 35 (p less than 0.05). The largest number of discontinuations comprised women discontinuing for menstrual problems in both groups. The life-table total discontinuation rate at 12 months was 52.0 for the Norinyl 1 + 35 group and 50.7 for the Norinyl 1 + 50 group. The lost-to-follow-up rates at 12 months were 17.8 for the Norinyl 1 + 35 group and 22.8 for the Norinyl 1 + 50 group. PMID- 2206019 TI - Management of IUD users with non-visible threads. PMID- 2206020 TI - The first 30 volumes of Advances in Enzyme Regulation. PMID- 2206021 TI - The histidine-containing dipeptides, carnosine and anserine: distribution, properties and biological significance. AB - The biological significance of histidine-containing dipeptides discovered within the composition of nitrogenous extracts of skeletal muscles at the beginning of this century is still open to question. The present investigation is concerned with the analysis of distribution and metabolism of these compounds with special reference to their effects on functional activity of membrane-linked enzymatic systems, stability of cellular membranes, muscle contractibility, etc. The proposed hypothesis on stabilizing properties of carnosine and related substances on biological membranes is based on the ability of the dipeptides to interact with lipid peroxidation products and active oxygen species and to prevent membrane damage. This remarkable antioxidative effect of carnosine reflects the high therapeutic value of this compound as an anti-inflammatory drug and a prominent tool in wound healing. PMID- 2206022 TI - Tiazofurin action in leukemia: evidence for down-regulation of oncogenes and synergism with retinoic acid. AB - New light was thrown on the action of tiazofurin in the treatment of end-stage leukemic patients and in leukemic cells in tissue culture. 1. In a population of 21 consecutive patients 50% responded to tiazofurin treatment, confirming the usefulness of this therapy in end-stage leukemia. 2. In leukemic patients treated with tiazofurin and allopurinol reciprocal action was manifested in the increase in hypoxanthine and the decrease in uric acid concentrations in the plasma. On discontinuation of allopurinol, hypoxanthine levels steeply declined but uric acid concentration increased slowly, taking days to reach pretreatment level. 3. With a new and sensitive method the concentration of the active metabolite of tiazofurin, TAD, was measured in the mononuclear cells of tiazofurin-treated patients. Approximately 5 to 13% of the plasma tiazofurin level was observed as TAD in the mononuclear cells. This TAD concentration was sufficient to account for the inhibition of IMP DH in these cells. 4. Tiazofurin or retinoic acid caused differentiation of HL-60 leukemic cells and inhibition of cell proliferation. 5. By treating leukemic cells incubated with tiazofurin or retinoic acid also with guanosine it was elucidated that the mechanism of the two drugs differed since only the tiazofurin effects were counteracted by guanosine. 6. Tiazofurin and retinoic acid together in HL-60 cells provided synergistic impact on differentiation and cytotoxicity. 7. Tiazofurin resulted in down regulation of the expression of ras and myc oncogenes in three systems: K562 human erythroleukemic cells, rat hepatoma 3924A cells and human HL-60 leukemia cells. 8. Because both tiazofurin and retinoic acid are licensed drugs, their potential use in combination chemotherapy may have clinical relevance in the treatment of end-stage leukemia where our earlier studies have demonstrated the usefulness of tiazofurin. PMID- 2206023 TI - New biological functions of intracellular proteases and their endogenous inhibitors as bioreactants. AB - Many unexpected biological functions as bioreactants of the intracellular proteases and their endogenous inhibitors have been found recently. Chymase and tryptase in histamine granules of mast cells and basophile cells play an important role in the process of IgE-mediated degranulation and in the formation of an allergic inflammation profile. Furthermore, the relationship between membrane proteases and their endogenous inhibitor has been taken up as a key and key-hole relation which plays an important role for special recognition apparatus of biological information like the relation of peptide hormones (growth factors) and their specific receptors. Amino acid sequences of the active site of trypstatin are homologous with the neutralizing epitope beta of gp120 of AIDS virus (HIV-1). The trypstatin and anti-tryptase M antibody inhibited syncytium formation in HIV infected Molt 4, clone 8 cells. Therefore, the relationship between tryptase M with trypstatin and the recognition site of epitope beta of HIV-1 with the receptor of helper T-cells are the common keys. The precursor of Alzheimer's deposition protein contains a Kunitz-type trypsin inhibitor domain. The A4-precursor proteins are located in axons of pyramidal neurons in brain and secretory granules of chromaffin cells in adrenal medulla. Those may be secreted into the extracellular milieu. We propose that the A4 inhibitor inhibits a special type of tryptase in the brain and disturbs the complete degradation of secreted A4-precursor protein causing amyloid deposition in alzheimer disease by abnormal proteolysis. Human c-Ha-ras p21 shows 58% homology with cystatin beta, an endogenous inhibitor of cathepsin. Actually, p21 inhibits cathepsin L specifically, but not cathepsin H, papain and cathepsin B. However, the metabolic significance of this inhibitory activity is still unknown. PMID- 2206025 TI - Regulation of metallothionein gene transcription by metals. PMID- 2206026 TI - Alternative nitrogenase. AB - Recently, it has been demonstrated that both A. vinelandii and A. chroococcum have the ability to synthesize several different nitrogen-fixing enzymes. Both species can produce a Mo- or V-containing nitrogenase while A. vinelandii can also generate an all-Fe form of the enzyme. Regardless of the source or form of the enzyme, all nitrogenases are composed of two separable proteins, called components 1 and 2, where component 2 is a highly conserved dimer containing a single [4Fe-4S] cluster. The major differences among the various forms of the enzyme are in component 1, the protein where substrate reduction occurs. This protein can exist in forms of four, five, or six subunits and can contain Mo, V or only Fe at the putative active site. Finally, there are also variations among the different enzyme systems regarding the paramagnetism of component 1 as well as the general substrate reduction patterns. While it is not yet known why these bacteria possess the ability to generate multiple forms of nitrogenase or which form of the enzyme has the greatest physiological importance, the existence of these various nitrogenases raises several other important questions. Specifically, how do Mo, V and Fe regulate the synthesis of each enzyme system, which genes are unique and which are common for these systems, and what roles, if any, do Mo, V and Fe play in catalysis? The fact that we can now use three different enzyme systems to investigate nitrogen fixation may greatly increase our ability to answer these questions and eventually understand the mechanism of this very important enzymatic reaction. PMID- 2206024 TI - Metalloregulatory proteins and molecular mechanisms of heavy metal signal transduction. AB - This review has considered what is known about the precise chemical mechanisms involved in the signal transduction of heavy metal ions. By reviewing what is known about general modes of signal transduction, we may draw parallels with the detection of and response to metal ions. In all forms of signal transduction, sensors and transducers are required. Yet, it is apparent that each system has unique features which undoubtedly are critical for the specific signal at hand. Within the context of metal-responsive systems, regardless of whether or not the metal ion is being sequestered, directly utilized, removed or otherwise, several examples of specific metalloregulatory proteins have been elucidated and are summarized in Table II. A close inspection of Table II reveals that in most signal transduction pathways for heavy metals, the presence of the metal ion causes a marked change in the nucleic acid binding capacity of the metalloregulatory protein. For example, the presence of iron results in the dissociation of a protein from iron responsive elements, thereby derepressing ferritin translation. In other instances, metal binding allows a metalloregulatory protein to associate with DNA to activate or repress transcription, as with ACE1 and Fur, respectively. In fact, to the authors' knowledge, it appears that all characterized ligand-responsive transcription factors change nucleic acid binding activity upon ligand binding. This change in affinity is a major feature of the mechanism for activation or repression by these receptors. In contrast, the mercuric ion metalloregulatory protein, MerR, operates by an entirely different transduction mechanism. MerR remains bound to its operator sequence in the presence and absence of mercuric ion, with only a slight increase in the dissociation rate constant in the presence of Hg(II). Furthermore, the site of MerR binding to the DNA is in a novel position for a prokaryotic activator, directly between the two sets of recognition sequences for RNA polymerase. Analysis of the protein-DNA interactions and transcriptional activity has demonstrated that MerR forms a complex with RNA polymerase in the absence of Hg(II) that is unstable and transcriptionally repressed. When Hg(II) is present in greater than nanomolar concentrations, a highly active transcription complex is formed at PT and a distortion at the center of the palindromic MerR binding site is detectable. Kinetic analysis has determined that, although no change in the binding of RNAP to PT is apparent, the presence of Hg(II) stimulates the rate of isomerization from the closed to the open transcription complex.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2206027 TI - Regulation of gene expression by mercury. PMID- 2206028 TI - Molecular aspects of regulation of high affinity iron absorption in microorganisms. PMID- 2206029 TI - Regulation of ferritin gene expression. PMID- 2206030 TI - Efficacy and tolerability of lovastatin in a six-month study: analysis by gender, age and hypertensive status. AB - This study reports the results of a 6-month, open-label multicenter study of the efficacy and tolerability of lovastatin, a 3-hydroxy-3-methylglutaryl co-enzyme A (HMG CoA) reductase inhibitor, in the management of nonfamilial primary hypercholesterolemia. The study enrolled 489 patients with elevated total serum cholesterol levels, whose lipids were not controlled sufficiently by diet. There was good representation of gender (48.3% women and 51.7% men), age (mean 57, range 25 to 83) and hypertension status (55.4% normotensive and 43.6% hypertensive) in the sample. Within 1 month of lovastatin therapy, total cholesterol was reduced 19% (from a mean of 269 to 217 mg/dl, low-density lipoprotein (LDL) cholesterol was reduced 27% (191 to 140 mg/dl), high-density lipoprotein (HDL) cholesterol increased 6% (42.6 to 45.1 mg/dl), the ratio of total cholesterol to HDL was reduced 24% (6.7 to 5.1) and the ratio of LDL to HDL was reduced 30% (4.7 to 3.3). These results were consistent across age group, gender and hypertension status, and were maintained for a period of 6 months of therapy. Lovastatin was generally well tolerated. Of the 489 patients enrolled, 449 (92%) completed 6 months of therapy. Only 21 (4%) withdrew because of adverse experience regardless of cause. None of the few serious adverse experiences (e.g., myocardial infarction) could be attributed to the drug. Abnormal laboratory values during the 6 months of therapy were within expectations. Seventy-four patients had at least 1 abnormal value during 6 months of treatment. Of these, 42 had at least 1 mild to moderate creatine phosphokinase elevation during this period. Only 1 patient had an adverse change on ophthalmologic examination: a posterior subcapsular opacity in both eyes just visible on 6-month examination. PMID- 2206031 TI - Extended clinical safety profile of lovastatin. AB - Lovastatin has been available for prescription use in the United States for about 20 months (as of June 1989). Over 1 million patients have received the prescription drug, and approximately 14,000 patients have participated in clinical trials. It is estimated that 500,000 patients have received lovastatin continuously for at least 1 year. This report reviews the extended safety experience from all clinical trials and prescription use. At least 645 patients have received lovastatin for more than 3 years. There are new data from a recently completed 1 year, placebo-controlled trial in 8,245 patients (Expanded Clinical Evaluation of Lovastatin study) and 20 months of health professionals' reports on spontaneous adverse events associated with large prescription usage. Data from recent large clinical trials suggest that the risk of myopathy and asymptomatic sustained liver transaminase elevations is less than reported in prior studies. The early clinical trials enrolled very high risk patients receiving lovastatin at a usual dose of 80 mg/day and often receiving concomitant hypolipidemic agents including gemfibrozil and niacin. After more than 42 months' long-term clinical trial experience, data have not established adverse effects from lovastatin on the human lens. Possible new types of rare drug-related adverse events observed with large prescription use include hypersensitivity reactions such as arthralgia, thrombocytopenia, symptomatic hepatitis and interaction with warfarin. No new, unique adverse-event profile has emerged with extended clinical use, including use in a few patients who have received therapy for more than 5 years. The lovastatin extended safety profile is that of a generally well-tolerated drug. PMID- 2206032 TI - Comparison of the effects of lovastatin and gemfibrozil on lipids and glucose control in non-insulin-dependent diabetes mellitus. AB - Patients with non-insulin dependent diabetes mellitus have an increased incidence of coronary artery disease which may, in part, be associated with abnormalities in plasma lipids. In a double-blind, parallel, randomized study, lovastatin and gemfibrozil were compared in 102 diabetic patients with primary hypercholesterolemia; two-thirds of the patients were treated with oral hypoglycemic agents and one-third received diet therapy alone for their diabetes. Mean pretreatment total and low-density lipoprotein (LDL) cholesterol values were 273 and 193 mg/dl, respectively. Lovastatin significantly reduced total, LDL and very low density lipoprotein cholesterol (20, 26 and 28%, respectively) and raised high-density lipoprotein (HDL) cholesterol (14%). Gemfibrozil significantly reduced triglycerides and very low density lipoprotein cholesterol (36 and 41%, respectively) and, to a lesser extent, total cholesterol (9%); it also increased HDL cholesterol (21%). Lovastatin therapy was not associated with a significant change in triglycerides, and gemfibrozil did not significantly lower LDL cholesterol. The decrease in the ratio of total to HDL cholesterol tended to be greater with lovastatin than with gemfibrozil (26.5 and 20.4%, respectively; p = 0.053). Changes in lipid profiles with both agents were of a degree similar to those reported in nondiabetic patients. Neither agent had a clinically important effect on fasting glucose or hemoglobin A1c. Both drugs were well tolerated with the exception of 2 patients treated with gemfibrozil who developed symptoms of cholecystitis. PMID- 2206033 TI - A multicenter comparison of lovastatin and probucol for treatment of severe primary hypercholesterolemia. The Lovastatin Study Group IV. AB - A multicenter study was undertaken to compare the effects of lovastatin (given in 4 different dosage regimens) and probucol in patients with severe primary hypercholesterolemia. The subjects were 290 patients taking lipid-lowering diets who were randomly assigned to 1 of the following treatment regimens for 14 weeks: lovastatin, 40 mg once a day with the morning meal (qam); lovastatin, 40 mg once a day with the evening meal (qpm); lovastatin 80 mg qpm; lovastatin, 40 mg twice daily, or probucol, 500 mg twice daily. One-third of the patients received probucol, and the other two-thirds were equally divided between the 4 lovastatin treatment groups. The mean reductions in total cholesterol in the 5 groups were, respectively, 20, 25, 30, 33 and 10%. The corresponding values for low-density lipoprotein cholesterol were 25, 32, 37, 40 and 8%. High-density lipoprotein cholesterol increased by 9 to 12% in all the lovastatin groups, but decreased by 23% in the probucol group. Triglycerides were reduced by 17 to 25% in all the lovastatin groups, but did not change significantly in the probucol group. Both drugs were well tolerated; no serious adverse events could be attributed to either agent. It is concluded that lovastatin is a considerably more effective lipid-lowering agent than probucol. In addition, lovastatin is almost as effective when given in a single daily dose as when given in a divided dose. When a once-a-day regimen is used, lovastatin is more effective if taken in the evening rather than the morning. PMID- 2206034 TI - Use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in various forms of dyslipidemia. AB - The inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase are highly effective in treating severe elevations of serum cholesterol, and are being widely used for this purpose. In our laboratory, these drugs have been used for the treatment of other forms of dyslipidemia including primary moderate hypercholesterolemia, primary mixed hyperlipidemia, diabetic dyslipidemia, hyperlipidemia of the nephrotic syndrome, and primary hypoalphalipoproteinemia. In these conditions, the HMG CoA reductase inhibitors proved effective in substantially decreasing levels of both low-density lipoproteins and very low density lipoproteins, as well as apolipoprotein B. In some patients, they may even increase levels of high-density lipoproteins. The primary mode of action of HMG CoA reductase inhibitors appears to be to increase the synthesis of hepatic receptors for lipoproteins containing apolipoprotein B, although a reduction in synthesis of these lipoproteins has not been ruled out with certainty. Regardless of mechanisms, drugs of this type appear to have the potential for effective therapy of various forms of dyslipidemia beyond primary severe hypercholesterolemia. PMID- 2206035 TI - Lovastatin and simvastatin prevention studies. AB - There is substantial evidence that drug treatment of hypercholesterolemia in patients without known coronary artery disease (CAD) can reduce fatal and nonfatal CAD events. Two trials, the Lipid Research Clinics Coronary Primary Prevention Trial and the Helsinki Heart Study used cholestyramine and gemfibrozil, respectively, to alter lipoprotein levels; their demonstrated efficacy and safety have led to their widespread use in hyperlipidemic patients. Recently, a new class of hypolipidemic agents has been shown to be extremely effective in lowering total and low-density lipoprotein cholesterol levels. These drugs, including lovastatin and simvastatin, competitively inhibit 3-hydroxy-3 methylglutaryl coenzyme A reductase, the rate-limiting enzyme of intracellular cholesterol synthesis. Results of safety and efficacy studies suggest that they may be valuable first-line treatment options for high-risk hypercholesterolemic patients. Two long-term clinical trials are planned with lovastatin and simvastatin. In the United States, lovastatin will be used in a double-blind, placebo-controlled, primary prevention trial involving 8,000 patients without clinical evidence of CAD, slight to moderate elevations of total cholesterol, and low- and high-density lipoprotein cholesterol to establish whether 5 years of treatment will decrease the rate of fatal CAD or nonfatal myocardial infarction. A Scandinavian study of 4,000 patients with ischemic heart disease and hypercholesterolemia will determine if simvastatin will improve total survival and reduce fatal or nonfatal myocardial infarction and sudden death for at least 3 years. These study designs will be discussed and compared with other studies, and the expected impact on CAD event rates presented. PMID- 2206036 TI - Expanded clinical evaluation of lovastatin (EXCEL) study: design and patient characteristics of a double-blind, placebo-controlled study in patients with moderate hypercholesterolemia. AB - The randomized, double-blind, placebo-controlled trial described in this report was undertaken to clarify the dose-response relation of lovastatin therapy to lipid-modifying efficacy (lipid/lipoprotein modification) and drug-related adverse events in a population with moderately elevated fasting plasma total cholesterol (240 to 300 mg/dl) and low-density lipoprotein cholesterol (greater than or equal to 160 mg/dl). Men or women (postmenopausal or surgically sterile), aged 18 to 70 years, were entered into the trial with minimal exclusion criteria. After 4 to 6 weeks of an American Heart Association phase I diet or a more stringent diet, 8,245 patients from 362 sites were randomized to 1 of 5 parallel diet and drug treatment groups: placebo (n = 1,663) or lovastatin, 20 mg (n = 1,642) and 40 mg (n = 1,645) with the evening meal, and 20 mg (n = 1,646) or 40 mg twice daily (n = 1,649). The regimen of diet and lovastatin (or placebo) was followed for 48 weeks. The 5 treatment groups were similar at baseline. The total cohort had the following characteristics: 59% were men (mean age 56 years); 92% were white; 59% had completed at least 1 year of education beyond high school; 57% had a history of cardiovascular and associated disease; 40% had a history of hypertension; and 29% had coronary artery disease. Health habits were similar among groups, with 18% of patients reporting cigarette smoking, 14% reporting that they consume greater than 1 alcoholic beverage daily and 67% reporting no strenous exercise. Mean lipid/lipoprotein levels were also similar among groups, with the following average levels: total cholesterol (258 mg/dl), low-density lipoprotein cholesterol (180 mg/dl), high-density lipoprotein cholesterol (45 mg/dl) and triglycerides (median = 155 mg/dl). The large size of this trial, its placebo-controlled, double-blind design and the similarity of treatment groups at baseline should allow clear documentation of the long-term effects of lovastatin treatment and generalization of the results to a substantial portion of patients who may be candidates for lipid-modifying therapy. PMID- 2206037 TI - Cornstarch ingestion after oral glucose loading: effect on glucose concentrations, hormone response, and symptoms in patients with postprandial hypoglycemic syndrome. AB - In susceptible individuals ingestion of glucose can lead to clinical symptoms of hypoglycemia as well as a reflex rise of counterregulatory hormones. We hypothesized that cornstarch, a slowly absorbed starch, might prevent hypoglycemic-symptom episodes. Eight patients who had characteristic signs, symptoms, and reflex hormonal responses of hypoglycemia at the glucose nadir after ingesting 75 g glucose (OGTT) participated. Patients ingested 75 g glucose followed by 75 g raw cornstarch (OGTT + CS). None of the patients reported symptoms or had signs of hypoglycemia in response to OGTT + CS. The glucose nadir concentration during OGTT + CS (3.8 +/- 0.6 mmol/L) was significantly higher than during OGTT (3.2 +/- 0.6; P less than 0.03). The responses of cortisol (331 +/- 166 nmol) and epinephrine (491 +/- 589 pmol/L) at the glucose nadir during OGTT + CS were significantly lower than the responses of cortisol (524 +/- 193 nmol/L; P less than 0.003) and epinephrine 1834 +/- 1135 pmol/L (P less than 0.0005) during OGTT. A slowly absorbed starch such as cornstarch may be an effective component in dietary management of this disorder. PMID- 2206038 TI - Fructans of Jerusalem artichokes: intestinal transport, absorption, fermentation, and influence on blood glucose, insulin, and C-peptide responses in healthy subjects. AB - Fructans are naturally occurring plant oligosaccharides with sweetening properties. Fructans (FAs) isolated from Jerusalem artichokes (Helianthus tuberosus) were studied with respect to intestinal handling and influence on blood glucose (BG), insulin, and C-peptide responses in eight healthy subjects. The responses were compared with those for fructose ingestion. The effect of FAs added to a wheat-starch meal was also studied. Standardized breath-hydrogen excretion indicated that FAs were completely malabsorbed and, after a 20-g dose, traces of FA were detected in 24-h urine collections in one subject only. Orocecal transit times were longer for FAs than for lactulose and fructose. The BG and insulin increments were very low after FA ingestion, lower than after fructose ingestion, whereas hydrogen production was much higher. Areas under BG curves tended to be smaller when 10 g FA was added to a 50-g wheat-starch meal, but there was no apparent interference with starch absorption. PMID- 2206039 TI - Orthodontic management of a patient with Class I malocclusion and severe crowding. PMID- 2206040 TI - A brief history of orthodontics. PMID- 2206041 TI - A clinical trial of an indirect bonding technique with a visible light-cured adhesive. AB - A trial was carried out to evaluate the clinical performance of a visible light cured adhesive when used with a foil mesh base in an indirect bonding technique. Thirty-seven patients entered the trial, and a total of 407 brackets were placed. The incidence and site of bond failure were recorded. The overall failure rate was 6.5%. There were no significant differences detected between the failure rates for either the upper or the lower arches or for the anterior and the posterior segments of the arches (p less than 0.01). PMID- 2206042 TI - Comparisons of different debonding techniques for ceramic brackets: an in vitro study. Part II. Findings and clinical implications. AB - A series of tests of three different debonding techniques applied to three different types of ceramic brackets revealed the following: (1) The incidence of bracket failure during debonding was significantly greater with conventional debonding recommended by the manufacturer (10-35%), as compared with the incidence associated with either the ultrasonic or the electrothermal methods (0%). (2) Bond failure at the bracket-adhesive interface occurred with significantly greater frequency for the Starfire brackets when debonding was performed with the electrothermal instrument and with significantly less frequency when the debonding pliers were used. Combination bond failures, in which part of the adhesive stayed on the enamel and part stayed on the bracket, occurred with significantly greater frequency when Transcend and Starfire brackets were debonded with debonding wrenches than when other methods were used. Combination-bond failures occurred with significantly less frequency when the brackets were removed with ultrasonic tips or with the electrothermal instrument. (3) The debonding times for the ultrasonic method were significantly greater than the times for either the conventional or the electrothermal methods. There were no significant differences among the debonding times for the three bracket types. There were no significant differences in the debonding times between the electrothermal method (means = 3.0 seconds) and the conventional bracket-removal method (means = 1.0 seconds). (4) Enamel loss as a result of adhesive removal was not significantly different among the three adhesive-removal techniques tested. Post-treatment roughness of the enamel surface was greater for the high-speed adhesive-removal technique than for either the low-speed or ultrasonic adhesive removal methods. PMID- 2206043 TI - A little bit of history: the first direct bonding in orthodontia. PMID- 2206044 TI - The association between alcohol intake and adiposity in the general population. PMID- 2206045 TI - Issues in agricultural health and safety. PMID- 2206046 TI - Epidemiologic studies of cancer in agricultural workers. AB - The incidence of cancer in agricultural workers is generally low, in part due to the low prevalence of cigarette smoking in this group. However, agricultural workers have elevated risks for several specific cancer types including leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, and cancers of the lip, stomach, prostate, brain, and connective tissue. Two major groups of risk factors have been proposed as causes of hematologic malignancies in agricultural workers. The first group includes various agricultural chemicals. In particular, several studies have found increased risks of malignant lymphoma and soft tissue sarcoma in persons exposed to phenoxy herbicides. However, the evidence is inconsistent and there is a wide variation in relative risk estimates. The second group of risk factors includes various animal viruses. There is currently little evidence concerning the zoonotic nature or human carcinogenicity of these viruses. However, leads have been suggested by recent evidence of increased risks of hematologic malignancies in abattoir workers, veterinarians, and meat inspectors. A third hypothesis, for which little evidence is currently available, is that agricultural work may involve prolonged antigenic stimulus leading to lymphoproliferation. The factors responsible for the increased risks for cancers other than hematologic malignancies are not well understood but may also involve exposure to chemicals or viruses. PMID- 2206047 TI - Occupational health services for farmers. AB - There are many unmet health needs in the farming community, needs that are peculiar to the agriculture industry. Health research and regulations to protect the safety of the farmer have lagged far behind those for other sectors of our economy. At a time when health needs are increasing, there is a decreasing availability of hospitals, physicians, nurses, and other health care personnel. The ability of the rural section to pay for these services is also declining. The evidence calls for a multifaceted solution, with improved cooperation and understanding on the part of the consumer as well as the provider. The regional health network is one system that may help solve some of these dilemmas. PMID- 2206048 TI - Injury surveillance in agriculture. AB - Information on agricultural trauma is limited and difficult to find. Planning for effective prevention strategies and evaluation is compromised by lack of a good surveillance system. Several agencies and organizations have provided some data. Although their summation is at best an approximation of the real situation, a critical review of current data bases is presented. The literature is also reviewed attempting to characterize agricultural trauma. This characterization was classified into: 1) case descriptions, 2) reviews of general articles on the hazards of farming, and 3) descriptive surveys of agricultural injuries. A summary of the available literature still leaves a rather superficial understanding of the entire injury picture. A new approach to surveillance is necessary to overcome past deficiencies. A combined modality approach is suggested, utilizing on-site survey, mail survey, telephone interviewing, and medical record verification. Trial applications of two such systems in Minnesota are described. PMID- 2206049 TI - Scope and magnitude of injuries in the agricultural workplace. AB - Agricultural work injury data are less available than data for other industries, so an overview of existing data is provided. Agriculture has the highest annual work death rate of all industries, 52 per 100,000 workers, which is five times the combined rate for all industries. Tractor-related injuries are the leading types of fatal injuries; injuries involving agricultural machinery, animals, and trucks are the leading types of non-fatal injuries. Victims of fatal accidents range in age from less than 1 year to over 90. Research needs are discussed, including the need for comprehensive surveillance. PMID- 2206050 TI - Role of the emergency department in decreasing the time to thrombolytic therapy in acute myocardial infarction. AB - The need to decrease the time to initiation of thrombolytic therapy for acute myocardial infarction (AMI) is described; treatment before hospitalization and in hospital emergency departments (EDs) is discussed. Delay from the onset of AMI symptoms to initiation of thrombolytic therapy can be reduced by improving (1) patient recognition of AMI symptoms and speed in seeking medical assistance and (2) the time that it takes for medical personnel to evaluate the patient's symptoms and to initiate appropriate therapy. Attempts to improve patient response to AMI symptoms have met with limited success. Pre-hospital administration of thrombolytic drugs may be of value, but it has the potential to shorten the time to thrombolytic therapy in only a minority of the affected population because many AMI patients are not transported by the emergency medical services system. The ED is a major focal point for influencing the timing of thrombolytic therapy. Much of what is known about the time sequence of thrombolytic therapy in EDs in the United States comes from organized trials in a small number of centers. Little is known about how often non-ED physicians participate in the decision-making process (either in person or by phone consultation), or how many delays are potentially avoidable. Current evidence suggests that pre-established ED treatment plans and protocols can lessen the time delay for many patients with AMI, especially if paramedics can transmit diagnostic-quality electrocardiograms to the hospital. PMID- 2206051 TI - Bleeding complications of thrombolytic treatment. AB - The mechanism and incidence of bleeding in patients undergoing fibrinolytic therapy are discussed, the role of laboratory findings in predicting the patient's clinical course is described, and guidelines concerning patient management are presented. Plasminogen activators have more similarities than differences in the mechanisms by which they dissolve thrombi and hemostatic plugs and, therefore, in their potential for vascular reperfusion or bleeding complications. The duration of an active lytic state in the blood varies according to the half-life of the activator; regardless of the agent chosen, however, plasma fibrinogen concentrations do not return to normal levels for one to two days following treatment. If plasminogen activator is still circulating, control of surgical bleeding after plasminogen activator treatment requires correction of the low plasma fibrinogen concentration with cryoprecipitate and administration of antifibrinolytic agents. Tests of coagulation and fibrinolysis can demonstrate a lytic state during therapy, but manipulation of drug therapy based on laboratory results is unlikely to control the patient's clinical course. Safe and effective therapy with plasminogen activators depends more on clinical judgment than on strict interpretation of laboratory test results. PMID- 2206052 TI - The pharmacist's role in thrombolytic therapy. AB - The pharmacist's role in the administration, appropriate use, and evaluation of thrombolytic agents is discussed. Thrombolytic drugs have been shown to be efficacious when given early in the development of an acute myocardial infarction (AMI). If the drug is to be reconstituted in a central area, there must be immediate response from the pharmacy. If reconstitution is not the pharmacist's responsibility, the pharmacist should still play a role in establishing guidelines for patient selection, drug reconstitution, patient-specific dosing regimens, and concomitant therapy. Pharmacists must also participate in drug-use evaluation. The three thrombolytic agents currently available for the management of AMI are streptokinase, alteplase, and anistreplase. Dosing and reconstitution guidelines for each of these agents are given, and current investigations concerning optimum regimens are summarized. Some of the relative contraindications now used in patient selection need to be examined. It is possible that certain patient subgroups excluded in some trials may benefit from thrombolytic agents. Future clinical trials will provide guidance for the use of thrombolytic agents in these populations. The advent of thrombolytic therapy offers pharmacy an opportunity to expand its role in the drug-use process and to ensure the appropriate use of these agents. PMID- 2206053 TI - Therapeutic management of acute myocardial infarction. AB - Criteria for selecting patients for thrombolytic therapy are presented, the major benefits of the currently approved thrombolytic agents are reviewed, and management considerations, including contraindications and the role of ancillary therapy, are discussed. Coronary thrombosis is now believed to play a central role in the pathogenesis of acute myocardial infarction (AMI). Re-establishment of coronary perfusion by thrombolysis has been extensively studied in the past decade and is now regarded as established therapy for patients with ischemic pain of brief (less than six hours') duration who have electrocardiographic ST-segment elevation, are less than 75 years of age, and have no contraindications. Studies supporting thrombolytic therapy have focused on the endpoints of (1) coronary artery patency or reperfusion, (2) improvement in left ventricular function, and (3) reduction in mortality. Benefits for each of these three endpoints have been established and are reviewed with respect to streptokinase, alteplase, and anistreplase, the three agents that have been approved for intravenous use in patients with AMI. The risk of bleeding, including intracranial hemorrhage, remains a concern for all patients. Ancillary therapies to be considered include aspirin, heparin, nitroglycerin, and beta blockers. Recent studies testing different strategies for coronary angiography and angioplasty plus surgery have generally supported a conservative approach, with interventions performed for clinical reasons rather than prophylaxis. Although the currently approved agents have differing pharmacologic profiles, none has yet proved to be clearly superior in the management of patients with AMI. Nonetheless, these agents remain the most promising means of treating selected patients. PMID- 2206054 TI - Insulin resistance and hypertension. AB - The author has reviewed the development of the concept that insulin resistance is related not only to the hypertensive state but potentially to the initiation and maintenance of high blood pressure. Potential sequelae of insulin resistance and hyperinsulinemia, as they apply to atherogenesis, are also discussed. The impact of present antihypertensive pharmacologic therapy on insulin resistance is addressed, as are future directions in pharmacologic and nonpharmacologic management of hypertension. In addition, the author speculates on possible mechanisms leading to insulin resistance in hypertension. PMID- 2206055 TI - Cases with ruptured membranes that "reseal". AB - Among patients with a diagnosis of preterm prepartal rupture of the membranes, an occasional case ceases to leak amniotic fluid before the onset of labor. The purpose of this case-control study was to determine the characteristics and obstetric outcomes of this unique group of patients. This diagnosis was made in 24 such patients who gave birth in 1984 and 1985 at Shands Hospital. Compared with matched control subjects who continued to leak fluid, there were no significant differences in maternal race, age, marital status, socioeconomic status, smoking status, or past obstetric performance. Amniotic fluid volumes, as assessed by ultrasound studies, were less in the group that failed to "reseal." The "reseal" group had longer durations of pregnancy, larger babies, longer maternal hospitalization, less neonatal hospitalization, and less perinatal mortality and morbidity. The occurrence of "resealing" appears to bode well for the mother and infant. Such cases should be sought aggressively but managed conservatively. PMID- 2206056 TI - The diagnostic values of concurrent nonstress testing, amniotic fluid measurement, and Doppler velocimetry in screening a general high-risk population. AB - To determine the values of individual and combined biophysical fetal surveillance tests in a general high-risk population, we examined 1000 consecutive pregnancies complicated by either postdatism, hypertension, intrauterine growth retardation, or diabetes mellitus. Nonstress tests, amniotic fluid pocket measurements, and umbilical artery Doppler velocimetry were performed on each patient; each test was rated against gestational age-adjusted standards. Clinical end points included perinatal mortality, intrapartum fetal distress, 5-minute Apgar score less than 7, and neonatal acidosis in pregnancies without major anomalies or extreme prematurity (age at birth greater than 32 weeks), delivered within 72 hours of final tests. Each testing method had specificity greater than 90%. Sensitivities ranged from 69% (nonstress test) to 21% (Doppler velocimetry). Negative predictive values of each method exceeded 85%; positive predictive values ranged from 81% (nonstress test) to 42% (amniotic fluid measurements). The positive predictive value for any abnormal test was 54% and increased to 100% when all tests were abnormal; this latter condition occurred in only 2% of the total population. Amniotic fluid measurements or Doppler velocimetry, when compared with the nonstress test, appeared to be less powerful "stand-alone" screening tests. The performance of all tests in a single session confers little improvement in detection of fetal compromise if the nonstress test is normal; however, this approach may aid decision-making in the management of pregnancies when fetal maturity is not established. PMID- 2206057 TI - Diagnosis and management of prenatally detected myelomeningocele: a preliminary report. AB - Our experience with 23 cases of fetal myelomeningocele provides preliminary information on the outcome of these infants diagnosed in utero and managed by a multidisciplinary team. The mean age of diagnosis was 23.7 weeks (range, 16 to 34 weeks). Mean gestational age at delivery was 36.9 weeks in the 14 patients who elected to continue their pregnancies. None of the 11 infants with lumbosacral or sacral lesions developed significant ventriculomegaly before term. Of the three patients diagnosed with thoracolumbar lesions, two had progression of ventriculomegaly necessitating early delivery at 32 to 34 weeks of gestation. These preliminary findings suggest that a coordinated prenatal and neonatal approach appears to result in a favorable prognosis for infants with myelomeningocele, but that neonatal complications are common, requiring careful monitoring and aggressive management. PMID- 2206058 TI - Effectiveness of 1% lidocaine dorsal penile nerve block in infant circumcision. AB - A prospective, controlled, double-blinded investigation was conducted to evaluate whether infants undergoing circumcisions with 1% lidocaine dorsal penile nerve blocks experienced decreased stress as compared with those receiving saline solution injections or no injections. Stress was measured in terms of pulse rate and oxygen saturation on a pulse oximeter. A subjective grading scale was also developed to measure infant irritability. The total number in the study was 51 with 23 infants in the lidocaine group, 21 in the saline solution group, and 7 in the no injection group. The results of the study revealed an average increase of 28.8% in the pulse rate above baseline for the control infants (p less than 0.001) versus no significant change in the lidocaine group. The average oxygen saturation of the control groups decreased by 5.6% from baseline (p less than 0.001), and that of the lidocaine group decreased by 1.0%, which was not a significant change. The subjective data were gained by using a grading scale of 1 to 6 with 1 being the least irritable infant and 6 being the most irritable infant. The physician evaluation gave an average rating of 4.2 to the control group versus 2.4 for the lidocaine group (p less than 0.001). The nursing evaluation during the procedure gave an average rating of 4.2 to the control group versus 2.3 to the anesthetized group (p less than 0.001). The subjective evaluation of infants before and after the procedure was not significantly different. There were no major complications in any of the groups. PMID- 2206059 TI - Early pregnancy failure--appropriate terminology. PMID- 2206060 TI - Vaginal probe ultrasonography and ectopic pregnancy. PMID- 2206061 TI - Fetal Doppler velocimetry in twins. PMID- 2206062 TI - Ultrasonographic dating of very early pregnancy. PMID- 2206063 TI - Ultrasonography's role in detection of intrauterine synechiae. PMID- 2206064 TI - Ultrasonographic evaluation of uteroplacental blood flow patterns of abnormally located and adherent placentas. AB - Transvaginal ultrasonography was used to evaluate antepartum bleeding in a group of 76 patients at varying gestational ages with suspected placenta previa. The clinical outcome of 16 patients with persistent placenta previa was documented. Nine of the 16 patients had placental lacunar blood flow. Two of the nine patients were lost to follow-up. At cesarean section the seven patients with lacunar flow had a higher incidence of blood loss, transfusion requirements, abnormally implanted placenta, and cesarean hysterectomy than the six patients in whom no lacunar flow patterns were seen (p = 0.002). The finding of these flow patterns with abnormally located placentas suggests the anticipation of significant blood loss and probable extension of operative procedures to stop the blood loss. PMID- 2206066 TI - Effect of tocolytic agents on fetal umbilical velocimetry. AB - In this prospective study, we sought to examine the changes in umbilical vascular resistance induced by tocolytic therapy. Umbilical artery velocimetry was performed in 46 patients with preterm labor before tocolysis and at 1 hour and 24 hours after tocolysis was initiated. Raw systolic/diastolic ratios were corrected for concomitant changes in fetal heart rate. Thirty patients received subcutaneous terbutaline and 16 were treated with intravenous magnesium. Systolic/diastolic ratios decreased in patients treated with terbutaline. This decline persisted after correction for increases in fetal heart rate. No significant changes in systolic/diastolic ratios were seen in patients treated with magnesium. We conclude that terbutaline may affect umbilical vascular resistance. Possible clinical implications of these findings are discussed. PMID- 2206065 TI - Antibiotic therapy in preterm premature rupture of membranes: a randomized, prospective, double-blind trial. AB - The use of antibiotics in the management of preterm, premature rupture of membranes remains controversial. By use of a prospective randomized double-blind design we investigated the maternal-fetal benefits associated with antibiotic therapy in 85 women with premature rupture of membranes at 34 weeks' estimated gestational age. In the treatment group 40 patients received intravenous mezlocillin for 48 hours followed by oral ampicillin until delivery. In the control group 45 patients received intravenous and oral placebo. Patients who received antibiotics had chorioamnionitis and endometritis less frequently than the control group (p less than 0.01 and p less than 0.05). Pathologic examination of the placentas showed a lower incidence of chorioamnionitis in the treatment group (p less than 0.05). The period from premature rupture of membranes to delivery (latency) was prolonged with antibiotics (p less than 0.05) and resulted in significant weight gain in the infants in the antibiotic group (p less than 0.0001). These infants also had higher 1- and 5-minute Apgar scores. Clinically suspected sepsis, respiratory distress syndrome, intraventricular hemorrhage, perinatal death rate, and prolonged hospitalization (greater than 30 days) were also increased in the control group. PMID- 2206067 TI - Does the umbilical artery systolic/diastolic ratio reflect flow or acidosis? An umbilical artery Doppler study of fetal sheep. AB - We studied four fetal sheep at 114 to 139 days' gestation to evaluate the effect of acute placental embolization on placental perfusion, fetal oxygenation and acid-base status, and the umbilical artery systolic/diastolic ratio. Studies were performed after maternal anesthesia was induced in an acute model, with serial umbilical artery embolizations performed at 20 to 30 minute intervals. Fetal umbilical flow, systolic/diastolic ratio, and arterial blood gas levels were followed up. One animal maintained a normal systolic/diastolic ratio despite a 50% drop in flow after the first injection and pH of 6.91, and died after the second injection. The remaining three animals showed significantly decreased flow after the third injection (p less than 0.02), with no change in the systolic/diastolic ratio. The systolic/diastolic ratio increased significantly after the fourth injection (p less than 0.05) when flow had dropped even further. Corresponding decreases in PO2 and pH did not achieve statistical significance. The magnitude of all changes increased with subsequent embolizations. We conclude that in this model significant reductions in flow result in small increases in the systolic/diastolic ratio and that greater magnitude changes in the systolic/diastolic ratio appear only with severely diminished flow and PO2, when acidosis develops. PMID- 2206068 TI - Superiority of the four-quadrant sum over the single-deepest-pocket technique in ultrasonographic identification of abnormal amniotic fluid volumes. AB - Ultrasonographic estimation of amniotic fluid volume is an important adjunct to assessment of fetal well-being. However, no single method has emerged as most predictive. Many ultrasonographers use subjective or single-pocket guidelines in evaluation of amniotic fluid volume. We therefore assessed the ability of a maximum-vertical-pocket technique to identify patients with abnormal volumes of amniotic fluid. A total of 1168 patients was studied. Oligohydramnios (n = 76) was defined as an amniotic fluid index less than 5th percentile for gestational age (70 to 98 mm). Hydramnios (n = 51) was defined when the amniotic fluid index was greater than 95th percentile (185 to 249 mm). The ability of the maximum vertical-pocket technique to identify cases with oligohydramnios by amniotic fluid index was poor: sensitivity was 42% and positive predictive value was 51%. Fifty-eight percent of cases with oligohydramnios by amniotic fluid index had "normal" values according to the single-pocket technique. The correlation coefficient between amniotic fluid index and maximum vertical pocket was 0.51, R2 = 24%. The correlation between the maximum vertical pocket and amniotic fluid index was somewhat better in cases of polyhydramnios (r = 0.79, R2 = 62%), but the sensitivity, positive predictive value, and false-negative rates were high as in oligohydramnios. These data suggest that the maximum-vertical-pocket technique has adequate specificity but is a poor screening tool. The results demonstrate that use of gestation-specific norms for the amniotic fluid index identifies abnormal amniotic fluid volumes more efficiently than the single-pocket technique. PMID- 2206069 TI - Randomized investigation of magnesium sulfate for prevention of preterm birth. AB - One hundred fifty-six women with preterm labor between 24 and 34 weeks' gestation were randomized to receive either intravenous magnesium sulfate or no tocolytic therapy. Magnesuim sulfate infusions of up to 3 gm/hr were used in 76 pregnancies and resulted in a mean serum magnesium concentration of 5.5 +/- 1.4 mEq/L (mean +/- SEM). Compared with 80 control pregnancies, magnesium sulfate tocolysis had no significant effect on duration of gestation, birth weight, neonatal morbidity, and perinatal mortality. We conclude that clinically safe infusions of magnesium sulfate are ineffective when used to prevent preterm birth. PMID- 2206070 TI - Fetal umbilical artery Doppler response to graded maternal aerobic exercise and subsequent maternal mean arterial blood pressure: predictive value for pregnancy induced hypertension. AB - Predictive tests for the identification of women at high risk of the development of preeclampsia are critical to allow the most appropriate preventive measures. Preeclampsia is a vasospastic condition of pregnancy characterized by early and enhanced vascular reactivity to endogenous pressor agents. Exercise tolerance testing with cycle ergometry to induce hemodynamic response measured with duplex Doppler A/B ratio of the umbilical artery could unmask latent vascular pressor hypersensitivity. Our prospective cohort study was designed to test the efficacy of the American College of Obstetricians and Gynecologists exercise in pregnancy guidelines for the low-risk athletic, physically active, or sedentary patient. The pattern of fetal response to material exercise testing at 28 weeks' gestation was compared with subsequent maternal mean arterial blood pressure and the development of pregnancy-induced hypertension and preeclampsia. Doppler A/B ratio during the recovery period was assessed as below baseline (18) or elevated above resting baseline values (12). Third-trimester blood pressure pattern was assessed to be elevated in 11 patients, 10 of whom had elevated recovery A/B ratios. The Fisher exact test results were (p = 0.00002) positive predictive value, 83%; negative predictive value, 94%; sensitivity, 91%; and specificity, 89%. Preeclampsia developed in four patients; all had elevated recovery A/B ratios. Fisher exact test results were (p = 0.01806) positive predictive value, 33%; negative predictive value, 100%; sensitivity, 100%; and specificity, 69%. PMID- 2206071 TI - The Shirodkar operation: a reappraisal. AB - Sixty-six cerclages were performed by one surgeon in 46 patients with documented cervical incompetence. The mean operative blood loss was 25 ml, and the mean operating time was 18 minutes with no postoperative morbidity. Fifty-five of the pregnancies were carried for at least 37 weeks, eight were delivered before 37 weeks, and three are continuing. Six of the eight preterm deliveries were a result of factors unrelated to cervical incompetence. The two remaining preterm births were probably also unrelated because one occurred 8 days after emergent cerclage placement and the other occurred 12 weeks after the procedure, both as a result of premature rupture of membranes. There were no cesarean deliveries related to the Shirodkar suture. The efficacy of the procedure was demonstrated by a corrected perinatal survival rate of 100% and term delivery of 88%. (Since this article was written all three of the undelivered patients were delivered of infants after 37 weeks' gestation for a term delivery rate of 88% with 100% neonatal survival. PMID- 2206072 TI - Double-blind comparison of intravaginal prostaglandin E2 gel and "chip" for preinduction cervical ripening. AB - The intravaginal application of prostaglandin E2 for preinduction cervical ripening has proved to be advantageous in the management of patients with an unfavorable cervix. The purpose of this double-blind randomized investigation was to compare the efficacy and safety of two methods of prostaglandin E2 delivery. Patients who were to have preinduction cervical ripening because of an unfavorable cervix (Bishop score less than or equal to 4) were randomly assigned to be given a single dose of prostaglandin E2 as either 2.5 mg of gel or a 3.0 mg "chip" intravaginally in a placebo-controlled manner. Sixty-nine patients received the active prostaglandin E2, 34 in the gel group and 35 in the "chip" group. The groups were similar in maternal age, race, parity, gestational age, and initial Bishop score. Both forms of prostaglandin E2 were easy to administer and helpful in priming an unfavorable cervix. The need for, duration of, and maximum dose of oxytocin were similar in both groups. Cesarean delivery because of failed induction occurred in 5 of 35 (14.3%) patients receiving a "chip" and 4 of 34 (11.8%) receiving the gel. However, patients receiving a "chip" experienced a 20% (7/35) incidence of hyperstimulation, compared with 2.9% (1/36) in those receiving the gel (p less than 0.05). The only case requiring immediate cesarean delivery because of intractable uterine hyperstimulation received a "chip." We conclude that both methods were effective for cervical ripening, but the lower incidence of uterine hyperstimulation seen with the gel would suggest that it is preferable to the "chip." PMID- 2206073 TI - Prediction of risk for preterm delivery by ultrasonographic measurement of cervical length. AB - Risk assessment for preterm delivery remains difficult, particularly among women with no prior history of preterm birth. We hypothesized that accurate assessment of cervical length by endovaginal ultrasonography could predict preterm delivery risk. A total of 178 patients with singleton gestations and without cervical incompetence were studied with transabdominal ultrasonography and endovaginal ultrasonographic cervical length measurement and manual vaginal examination of cervical length. A total of 113 patients who were evaluated by 30 weeks' gestation (excluding four induced preterm deliveries) were analyzed. Preterm delivery risk was compared between women with cervical lengths equal to or greater than the median and those with cervical lengths less than the median. An endovaginal ultrasonographic cervical measurement less than 39 mm was associated with a significantly increased risk of preterm delivery (25.0% versus 6.7%) and detected 76% of preterm births. Manual examination of cervical effacement detected 71% of preterm births, but transabdominal ultrasonographic measurement of cervical length was not preditive. Endovaginal ultrasonographic cervical measurement predicted increased preterm delivery risk regardless of parity or obstetric history. Endovaginal ultrasonography is a promising method for the prediction of risk of preterm birth. Because it has the potential to be an objective measure of cervical length, endovaginal ultrasonography may be superior to manual digital examination for preterm delivery risk assessment. PMID- 2206074 TI - Is indicated or spontaneous preterm delivery more advantageous for the fetus? AB - We performed a case-control study to determine whether fetuses delivered prematurely because of pregnancy complications (primarily pregnancy-associated hypertensive disease) had a different neonatal course than that of those born after either spontaneous preterm labor or after premature rupture of the membranes. Two case-control populations were matched by gestational age at delivery, fetal sex, and race. There was no perinatal survival advantage in babies delivered from "stressed" pregnancies. Selected neonatal morbidities were generally similar, but there was an increased incidence of necrotizing enterocolitis in babies born after preterm labor and a higher incidence of both necrotizing enterocolitis and neonatal sepsis after premature rupture of the membranes. We conclude that a "stressed" pregnancy confers a negligible survival advantage to the fetus. PMID- 2206076 TI - A prospective randomized comparison of oral terbutaline and magnesium oxide for the maintenance of tocolysis. AB - We compared oral magnesium oxide with oral terbutaline sulfate in a prospective, randomized manner to determine efficacy and side effects. Preterm labor patients whose labor was arrested with parenteral tocolysis were randomized to oral tocolysis with either magnesium oxide, 200 mg every 3 to 4 hours (n = 23), or terbutaline, 2.5 to 5 mg every 3 to 4 hours (n = 27). The number of patients who were delivered of infants before 36 weeks' gestation was similar between groups (18.5% receiving terbutaline versus 17.4% receiving magnesium). At least one side effect occurred in 81.5% of patients in the terbutaline group and 47.8% in the magnesium group (p less than 0.01). Finally, the cost for 1 day of magnesium (20 cents) is approximately one third the cost of terbutaline (56 cents). These data suggest that oral magnesium oxide is as effective as terbutaline for the maintenance of tocolysis, with fewer side effects and at a lower cost. PMID- 2206075 TI - Evaluation of a risk scoring system as a predictor of preterm birth in an indigent population. AB - A risk scoring system designed to predict spontaneous preterm birth was implemented in a large, indigent population as part of a multicenter trial of preterm birth prevention. A total of 7478 women with singleton gestations were screened and followed up prospectively at the Birmingham project center. Patients who had an indicated preterm delivery or a fetal anomaly were excluded from the study population. Analysis by assigned risk score and parity showed that, whereas the sensitivity and positive predictive value were better in multiparous women than in nulliparous women, overall the values were low. Logistic regression analyses of the multiparous and nulliparous populations showed independent sets of significant (p less than or equal to 0.05) risk variables. A history of preterm delivery and a low prepregnancy weight were the most predictive risk factors in the multiparous and nulliparous models, respectively. We conclude that the clinical usefulness of a risk scoring system to predict spontaneous preterm birth in an indigent population is limited. PMID- 2206077 TI - Infants of diabetic mothers with accelerated fetal growth by ultrasonography: are they all alike? AB - We studied longitudinal ultrasonographic growth patterns (abdominal circumference, biparietal diameter) initiated early in gestation in 52 pregnancies complicated by pregestational diabetes mellitus and 19 controls. Three predominant patterns of growth were ascertained including a heretofore unrecognized pattern characterized by accelerated abdominal circumference growth (greater than 90th percentile) before 24 weeks' gestational age. Maternal and neonatal anthropometric and metabolic parameters were contrasted for the three patterns. The findings suggest that in some cases of diabetic macrosomia that can be recognized before 24 weeks' gestation, augmented growth may be influenced by factors other than fetal hyperinsulinism. PMID- 2206078 TI - Perinatal outcome of forty-nine pregnancies complicated by acardiac twinning. AB - Acardiac twinning affects 1 in 100 monozygotic twin pregnancies and 1 in 35,000 pregnancies overall. The presence of an acadiac twin requires the normal (or "pump") twin to provide circulation for itself, as well as the acardiac sibling. In many cases the acardiac twin is almost equal to the normal twin. The principal perinatal problems associated with acardiac twinning are pump-twin congestive heart failure, maternal hydramnios, and preterm delivery. We reviewed the perinatal courses of 49 acardiac twin pregnancies to identify factors prognostic of favorable outcome. The overall perinatal mortality was 55%, primarily associated with prematurity. Mean (+/- SD) gestational age at delivery was 29 +/- 7.3 weeks, with a mean (+/- SD) normal twin weight of 1378 +/- 1047 gm. The acardiac weight averaged 651 +/- 571 gm. However, the occurrence of hydramnios, the occurrence of preterm labor, and perinatal outcome were strongly related to the ratio of the acardiac and pump-twin's weight. The mean overall ratio of the twin weights was 52% +/- 42%. However, the mean weight ratio for patients delivered before 34 weeks was 60% versus 29% (p less than 0.04). Preterm delivery was strongly associated with the development of hydramnios and congestive heart failure in the pump twin (p less than 0.01). If the twin-weight ratio was above 70% (25% of cases), the incidence of preterm delivery was 90%; hydramnios, 40%; and pump-twin congestive heart failure, 30% compared with 75%, 30%, and 10%, respectively, when the ratio was less (p less than 0.05). Regression of the weight of the acardiac twin against its longest dimension (L) resulted in this equation for prediction of acardiac weight: Weight (grams) = 1.2 L2-1.7L; r = 0.79, p less than 0.01. These data suggest that estimation of the relative weights in acardiac twins provides prognostic information regarding outcome. Poor outcome occurs with congestive heart failure and hydramnios in the normal twin. Use of the above data may assist in counseling patients and determining optimal management. PMID- 2206079 TI - Ultrasonographic fetal weight estimation by an integrated computer-assisted system: can each laboratory improve its accuracy? AB - Estimated fetal weights from 1684 cases with singleton, live infants born within 7 days of an ultrasonographic examinations were compared with their birth weights, which ranged from 520 to 5920 gm. Estimated weight calculated from Shepard's equation produced a linear relationship of birth weight against estimated weight with an intercept and slope of 209.5 gm and 0.929. Overall, 75% of the estimated weights were within 15% of the actual weight. A separate regression model that used the same variables from Shepard's equation failed to improve the comparison between estimated and actual weights. All cases were reevaluated with multiple regression modeling. Various examination-to-birth intervals were analyzed; intervals less than or equal to 3 days appeared optimal. The best equation increased the percent of cases that were within 15% of the actual birth weight to 80%. The plot of birth weight against estimated weight had an intercept and slope of 33.1 gm and 0.994. Unlike Shepard's equation, the best equation was not statistically different from the ideal one-to-one relationship between estimated and actual weight. When the new equation was applied to an additional 339 new cases, equally accurate results were obtained. Customizing a laboratory's ultrasonographic weight estimation equations may be necessary to obtain the best estimate of fetal weight. PMID- 2206080 TI - Primary surgical treatment of anterior cruciate ligament ruptures. A long-term follow-up study. AB - We reviewed 52 patients who underwent primary surgical repair of their acutely injured ACL using a multiple loop, varying depth suture technique. The average followup was 6 years and 10 months. Nine patients (17%) were considered as having failed repairs, with failure based on the presence of clinical instability (giving way) with sports participation and a positive Lachman test and/or pivot shift maneuver. In addition, of 26 patients in whom KT-1000 (MEDmetric Corp., San Diego, CA) measurements were performed, 42% were found to have abnormal laxity. Although using multiple sutures in primary repair of the anterior cruciate may work in some patients, it is an unpredictable operative procedure and resulted in a 17% failure rate in our study. PMID- 2206081 TI - Living with artificial grass: a knowledge update. Part 1: Basic science. AB - Part I of this two part study reviews the development and characteristics of artificial grass, and the influence of this surface on the American football player. Artificial grass was initially developed to provide city children with increased play space and thus enable them to maintain a fitness level equal to their peers in more rural locales. Today, artificial grass fields allow for increased use when field availability is limited, or for a grass substitute where grass will not grow. However, epidemiologic studies suggest that there is an increased risk of lower extremity injury to the football athlete playing on an artificial grass field. By reviewing available studies, a knowledge base can be formed that can serve to direct future investigations concerning the influence of artificial grass surfaces and injury and, ultimately, how that influence can be affected. PMID- 2206082 TI - Complete rupture of the hamstring origin from a water skiing injury. PMID- 2206083 TI - Cystic endocervical tunnel clusters. A clinicopathologic study of 29 cases of so called adenomatous hyperplasia. AB - The clinical and histologic features of cystic endocervical tunnel clusters (CETC) are not well known. Unwary pathologists have sometimes mistaken CETC for endocervical adenocarcinoma or interpreted them as "adenomatous hyperplasia." In this study, CETC were identified in 19 (5.9%) of 322 consecutive hysterectomy specimens and three (9.7%) of 31 consecutive cervical conization specimens accessioned during a 1-year period. These 22 cases were analyzed along with seven consultation cases. The 29 patients' ages ranged from 33 to 72 years (mean, 55). All but one (96.6%) were multigravida. Almost 80% of the patients had had at least three previous pregnancies. The mean gravidity and age of the hysterectomy patients with CETC were significantly greater than those without them. CETC typically were discovered incidentally during routine examination of the cervix. The clusters ranged from 0.5 to 18.8 mm (mean, 2.4 mm) in greatest dimension; they were multifocal in 82.8% of cases. CETC consisted of orderly, lobular aggregates of closely packed, dilated tubular endocervical "glands" within the superficial endocervix. The deepest clusters extended to a depth of 9.0 mm. They were commonly associated with multiple Nabothian cysts, which occasionally also penetrated deeply. The lining epithelium was a single layer of flattened or cuboidal endocervical cells. Mitotic figures and significant cytologic atypia were absent. None of the cases had intracytoplasmic CEA immunoreactivity, but in 52% focal positive CEA staining was noted along the luminal border of the endocervical cells. CETC are believed to result from subinvolution of previous episodes of physiologic hyperplasia of the endocervical mucosa, usually due to prior pregnancies. They are unrelated to cervical neoplasms and must be distinguished from adenocarcinoma and other glandular lesions of the endocervix. PMID- 2206084 TI - Primary cutaneous rhabdomyosarcoma. AB - We report an unusual case of primary cutaneous embryonal rhabdomyosarcoma presenting as a solitary skin lesion on the anterior chest of a 20-month-old child. The tumor was characterized by small, round to oval, poorly differentiated cells. Immunohistochemically, the tumor was negative for NSE, S-100 protein, LCA, and keratin but positive for muscle-specific actin, myoglobin, desmin, and vimentin, thus indicating the presence of myogenous differentiation. Ultrastructural analysis demonstrated thick and thin filaments. Special studies showed no evidence of a primary rhabdomyosarcoma in the patient at a more typical location, nor was there any evidence of metastases. PMID- 2206085 TI - Sarcomatoid variant of anaplastic large-cell Ki-1 lymphoma. AB - Although anaplastic large-cell Ki-1 lymphomas can mimic a variety of tumors, a correct diagnosis is usually not difficult to reach if it is recognized that lymphoma cells can assume bizarre and pleomorphic appearances and that the pattern of growth can be purely sinusoidal. We report a unique case of a 45-year old man presenting with a leg lesion that showed sarcomatoid growth patterns. The subcutaneous/dermal tumor displayed a myxoid stroma reminiscent of myxoid malignant fibrous histiocytoma. In a subsequent lymph node biopsy, a well developed storiform pattern was formed by interweaving fascicles of plump spindle and oval neoplastic cells, reminiscent of pleomorphic/storiform type of malignant fibrous histiocytoma. The lymphoid nature of the tumor cells was documented by immunoreactivity for leukocyte common antigen, Ki-1 antigen, and the T-cell marker UCHL1. We conclude that the presence of a storiform or myxoid pattern does not disqualify the diagnosis of lymphoma; this possibility should always be pursued in pleomorphic tumors because the treatment is substantially different from that for sarcoma, carcinoma, or melanoma. PMID- 2206086 TI - Dermatomyositis and polymyositis in childhood. AB - Personal experience of 30 years work with 40-50 cases of dermatomyositis and polymyositis in childhood is reviewed, stressing the clinical findings of skin eruptions on the knuckles, elbows and knees (except in the 10 per cent of patients without any skin involvement), weakness of particularly proximal muscles and tightness of tendons. Special diagnostic procedures are reviewed as well as treatment. The basic treatment is corticosteroids, which must be started at a high dose and as soon as possible be given at intervals of 48 hours to diminish the side-effects. In many, though not all, patients the treatment must be continued for years. The parents should always know that extended treatment may be necessary. Physiotherapy should be started cautiously and be slowly increased, close co-operation between the physician and the physiotherapist being necessary. If the patient does not respond to corticosteroids, antimetabolites may be added. Most patients survive with no or only minor sequelae. PMID- 2206087 TI - Occlusive dressings: a microbiologic and clinical review. AB - This review discusses the microbiology of normal skin and wounds and examines the rates of infection reported under both conventional (nonocclusive) dressings and all occlusive dressings, together with cost factors. The overall infection rate under conventional dressings was 7.1% in 1085 wounds, whereas under occlusive dressings on 3047 wounds the rate was 2.6%. In studies in which the two dressing types were directly compared, the respective rates were 7.6% and 3.2%. The reasons for this difference may include both dressing-specific and host-specific factors, and these factors are discussed. PMID- 2206088 TI - Physician payment reform: how it will affect allergists. PMID- 2206089 TI - Occupational asthma. PMID- 2206090 TI - Relationship between recurrent croup and airway hyperreactivity. AB - The relationship between recurrent croup and bronchial asthma was evaluated by measuring bronchial hyperreactivity (methacholine challenge), physiologic parameters of upper airway obstruction, and skin response to environmental allergens. Patients with recurrent croup (n = 10) had a significantly higher degree of airway hyperreactivity and atopy than healthy children (n = 15), but significantly less than the patients with bronchial asthma (n = 30). No physiologic signs of upper airway obstruction could be detected at rest or following methacholine. It is suggested that bronchial asthma and recurrent croup share a few characteristics. PMID- 2206092 TI - Microalbuminuria in diabetes mellitus: review and recommendations for the measurement of albumin in urine. PMID- 2206091 TI - Biochemical investigation of hypertension. AB - Underlying causes of hypertension are found in less than 5% of cases but they are frequently surgically remediable. Elementary biochemical tests are usually sufficient to exclude most renal and endocrine causes of hypertension. However, young patients with very high blood pressures merit more detailed investigation in specialized centres. As coexistent hyperlipidaemia or glucose intolerance substantially worsen the prognosis for a given level of blood pressure, these two risk factors are worth assessing in all hypertensive patients. Their presence may also alter the choice of antihypertensive drug therapy. About 25% of the population have raised blood pressure at first screening and about 10% are in need of drug therapy, so this represents an appreciable load on biochemical laboratories. Most patients, however, need only a single biochemical profile on one occasion, and should be exclusively managed in general practice. PMID- 2206093 TI - Drug interference in the measurement of serum fructosamine. PMID- 2206094 TI - Liver disease associated with pregnancy. AB - Pregnancy is associated with altered liver function, particularly in serum enzymes. Anabolic steroids are responsible to some degree in mediating the physiologic and biochemical changes that occur during an uncomplicated pregnancy. However, several liver disorders are unique to pregnancy and include intrahepatic cholestasis of pregnancy, acute fatty liver of pregnancy, and hepatic dysfunction associated with pre-eclampsia and eclampsia. It is imperative for the clinician to diagnose these liver disorders in a timely manner and to institute appropriate management as maternal and fetal outcome are affected in an adverse manner if these conditions are left untreated. PMID- 2206095 TI - Surgical resection versus perfusion in the treatment of metastatic and primary liver tumors. AB - The involvement of the liver by malignancy, whether it be primary or metastatic, carries a grave prognosis. At this time, chemotherapy is solely palliative, and no survival advantage has been established. Resection of metastatic or primary carcinoma of the liver in a select number of patients may provide a survival advantage and an occasional cure. However, studies are difficult to control, and claims of survival benefits have been based on historical data of untreated disease prior to 1978. Currently, clinical trials are underway combining modes of therapy in the hope of increasing patient survival. Reduction of operative mortality to below five percent for liver resection is attributable to a major advance in operative technique. Other advances are improved diagnostic techniques for detection of liver metastases and selection of patients for resection. Finally, newer strategies for chemotherapy made practicable continuous infusion by implantable or external pumps, redoubling response rates to fluorodeoxyuridine (FUDR) in regional and 5-fluorouracil (5-FU) in systemic chemotherapy. A review of the current literature is presented along with data accumulated over the three year experience of the Moffitt Cancer Center, Tampa, Florida. The case material from Moffitt Cancer Center is included to illustrate progress and limitations of combined surgical, regional, and systemic chemotherapy for primary and metastatic liver cancers. PMID- 2206096 TI - The prediction of autologous red cell survival. AB - Nine donors predicted from earlier studies to have increased autologous red cell survival and four predicted to have lesser survival were selected from a pool of previously studied donors. Blood was drawn from these donors, and stored in Neutracel (R-Cutter Lab) preservative for eight hours at room temperature. The platelet rich plasma was removed, the additive solution was introduced, and the red cells were stored for 42 days in an approved refrigerator. At the end of the storage period, a 24 hour Cr-51 viability analysis was performed on each donor. Predicted red cell survival scores correlated reasonably well with the observed percent of red cell viability (r = 0.648). This study suggests that it may be possible to predict increased viability of autologous red cells in certain donors. PMID- 2206097 TI - Effect of malnutrition and hormone treatments on intestinal microvillus membrane glycosylation in suckling rats. AB - Imposition of undernutrition in suckling rats significantly enhanced (p less than 0.001) sialic acid and reduced (p less than 0.001) fucose contents of intestinal microvillus membranes (MVM) compared to the controls. Administration of cortisone or insulin to undernourished (UN) pups reversed the sialylation and fucosylation pattern of the membranes. The binding of wheat germ agglutinin (WGA) to membranes was increased (p less than 0.001) and that of Ulex europeus agglutinin (UEA) was decreased in nutritionally deprived pups. Cortisone and insulin treatments reduced WGA and enhanced UEA bindings to UN membranes. The binding of peanut agglutinin (PNA) to UN membranes was 60% higher compared to that in the control rats. Cortisone and insulin treatments further enhanced PNA binding to the brush borders in UN pups. The incorporation of 14C-GlcNAc, 14C-mannose and 3H-fucose into MVM was reduced by 32-57% in UN suckling rats compared to the controls. The incorporation of labelled sugars into membranes from 21- and 50- to 60-day-old rats was essentially similar. Cortisone administration to UN pups augmented the incorporation of labelled GlcNAc and mannose but had no effect on fucose incorporation. Insulin treatment of UN pups insignificantly elevated GlcNAc incorporation into the membranes. These findings suggest that imposition of UN during early suckling period delays the maturational development of intestinal glycosylation. Cortisone and insulin induced adult-type glycosylation pattern of the brush borders in nutritionally deprived pups. PMID- 2206098 TI - Effects of meal size reduction on postprandial variables in male volunteers. AB - To investigate the effects of meal size reduction on postprandial variables, adult male volunteers consumed at noon hot lunches composed of cooked white rice, fried chicken fillet, raisins, bigarreaus and curry sauce with carbohydrate/fat ratios of either 0.77 or 2.04 (37-57 en% carbohydrate, respectively). Prior to the actual experiment, the individual meal sizes were determined by allowing the volunteers to eat a self-preferred amount of the high carbohydrate meal. The test meals were adjusted to either 70 or 100% of the energy content of this individually chosen meal size. A higher degree of satiety was detected up to 4 h after the 100%-size carbohydrate-rich meal as compared to that after the fat-rich meals and the 70%-size carbohydrate-rich meal. The reduction in meal size had only small effects on the postprandial curves of glucose, insulin, free fatty acid and total glycerol in the blood relative to those induced by the variation in carbohydrate/fat ratio in the meals. No significant effects of meal size were detected on the postprandial curve of free glycerol. Thus limited restriction in the size of a meal relative to the ad libitum intake of an individual may be expected to lead to only minor effects on the various postprandial curves in meal eating studies. PMID- 2206099 TI - Nutritional value and intestinal effects of dipeptides and tripeptides. Comparison with their issuing bovine plasma protein in rats. AB - A hydrolysate containing 75% di- and tripeptides (DTP) was prepared from bovine plasma proteins (BP) and the original protein and hydrolysate were compared for nutritional value. Food intake, protein efficiency ratio (PER), nitrogen balance and digestibility and plasma amino acid concentrations were measured in young rats receiving the diets over 17 days. Moreover, intestinal adaptation was evaluated in duodenum, jejunum and ileum, with the aid of light microscopy and enzyme analyses; tritiated thymidine incorporation was also measured. In DTP- and BP-fed rats, food intake, body weight gain, nitrogen balance and digestibility as well as PER were similar. Plasma amino acid concentration analyses showed an increased concentration of threonine and valine in the BP-fed group. Measurements of mucosal enzyme activities suggest adaptation to the diets especially in the ileum as indicated by increasing aminopeptidase N and dipeptidyl peptidase IV specific activities in the BP-fed group. This group also displayed substantial 3H thymidine incorporation. It is concluded that the hydrolysate containing di- and tripeptides is efficiently utilized in healthy growing rats, though the efficacy is not higher than with the BP diet except for the difference in 3H-thymidine incorporation. PMID- 2206100 TI - Detection of Vibrio cholerae O1 in the aquatic environment by fluorescent monoclonal antibody and culture methods. AB - Vibrio cholerae O1 in plankton samples collected from ponds and rivers between February 1987 and January 1990 in Matlab, Bangladesh, was detected by the fluorescent-monoclonal antibody (FA) technique. Samples were collected at sites which were monitored fortnightly (fixed sites) as well as at sites that were part of a case-control study. FA results were compared with those obtained by conventional culture methods (CM). A total of 876 samples were collected; V. cholerae O1 was detected in 563 samples (64.27%) by the FA method and in 3 samples (0.34%) by CM. Of the fixed-site plankton samples, 439 (63.62%) were positive by FA and none were positive by CM. Of the 93 case sites sampled on the day after the occurrence of a case of cholera, 73 (78.49%) were positive for V. cholerae O1 by FA and 3 (3.2%) were positive by CM. In comparison, of the 93 first-day sample collections at control sites at the time a case of cholera occurred, only 51 (54.83%) were positive by FA and none were positive by CM. From the data, it is concluded that V. cholerae O1 is present throughout the year in the ponds and rivers of Bangladesh that were examined in this study and that V. cholerae can be detected by FA but not always by CM. The FA procedure was found to be very useful in detecting V. cholerae in plankton, with which it was associated and often occurred in large numbers in the nonculturable stage. Thus, studies investigating the significance of the role of environmental factors in the epidemiology of cholera can be performed effectively by using FA. Such studies are in progress. PMID- 2206102 TI - Isolation of Candida tropicalis auxotrophic mutants. AB - An enrichment scheme using nystatin was designed for the isolation of auxotrophic mutants from the diploid-alkane-utilizing yeast Candida tropicalis. A collection of 194 auxotrophs representing 7 phenotypes was isolated. One class of mutants was identified as having a defect in histidinol dehydrogenase activity and a second class of mutants was identified as having a defect in orotidine monophosphate decarboxylase activity. These strains are good candidates to be carrying mutations corresponding to the HIS4 and URA3 genes of Saccharomyces cerevisiae. PMID- 2206101 TI - Gene escape model: transfer of heavy metal resistance genes from Escherichia coli to Alcaligenes eutrophus on agar plates and in soil samples. AB - Conjugal transfer from Escherichia coli to Alcaligenes eutrophus of the A. eutrophus genes coding for plasmid-borne resistance to cadmium, cobalt, and zinc (czc genes) was investigated on agar plates and in soil samples. This czc fragment is not expressed in the donor strain, E. coli, but it is expressed in the recipient strain, A. eutrophus. Hence, expression of heavy metal resistance by cells plated on a medium containing heavy metals represents escape of the czc genes. The two plasmids into which this DNA fragment has been cloned previously and which were used in these experiments are the nonconjugative, mobilizable plasmid pDN705 and the nonconjugative, nonmobilizable plasmid pMOL149. In plate matings at 28 to 30 degrees C, the direct mobilization of pDN705 occurred at a frequency of 2.4 x 10(-2) per recipient, and the mobilization of the same plasmid by means of the IncP1 conjugative plasmids RP4 or pULB113 (present either in a third cell [triparental cross] or in the recipient strain itself [retromobilization]) occurred at average frequencies of 8 x 10(-4) and 2 x 10(-5) per recipient, respectively. The czc genes cloned into the Tra- Mob- plasmid pMOL149 were transferred at a frequency of 10(-7) to 10(-8) and only by means of plasmid pULB113. The direct mobilization of pDN705 was further investigated in sandy, sandy-loam, and clay soils. In sterile soils, transfer frequencies at 20 degrees C were highest in the sandy-loam soil (10(-5) per recipient) and were enhanced in all soils by the addition of easily metabolizable nutrients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206103 TI - Construction of a new catabolic pathway for D-fructose in Escherichia coli K12 using an L-sorbose-specific enzyme from Klebsiella pneumoniae. AB - Starting with a fruK (formerly fpk) mutant of Escherichia coli K12 lacking D fructose-1-phosphate kinase (E.C. 2.7.1.3.), fructose positive derivatives were isolated after introduction of the cloned gene sorE from Klebsiella pneumoniae coding for an L-sorbose-1-phosphate reductase. The new pathway was shwon to proceed from D-fructose via D-fructose-1-phosphate and D-mannitol-1-phosphate to D-fructose 6-phosphate. It involves a transport system and enzymes encoded in the fru and the mtl operons from E. coli K12 as well as in the sor operon from K. pneumoniae respectively. PMID- 2206104 TI - Killer toxin of Hanseniaspora uvarum. AB - The yeast Hanseniaspora uvarum liberates a killer toxin lethal to sensitive strains of the species Saccharomyces cerevisiae. Secretion of this killer toxin was inhibited by tunicamycin, an inhibitor of N-glycosylation, although the mature killer protein did not show any detectable carbohydrate structures. Culture supernatants of the killer strain were concentrated by ultrafiltration and the extracellular killer toxin was precipitated with ethanol and purified by ion exchange chromatography. SDS-PAGE of the electrophoretically homogenous killer protein indicated an apparent molecular mass of 18,000. Additional investigations of the primary toxin binding sites within the cell wall of sensitive yeast strains showed that the killer toxin of Hanseniaspora uvarum is bound by beta-1, 6-D-glucans. PMID- 2206105 TI - [Intraventricular hemorrhage in utero]. AB - A case of fetal intraventricular hemorrhage related to subependymal hemorrhage diagnosed by ultrasound scanning at 27 weeks of PMA is reported. No etiology was found. The outcome was favorable. This case suggests that some cases of neonatal idiopathic hydrocephalus may be explained by fetal subependymal/intraventricular hemorrhage. PMID- 2206106 TI - [Proteus syndrome]. AB - Two new cases of Proteus syndrome are reported. This congenital syndrome, first described in 1983, comprises gigantism of extremities, body hemihypertrophy, pigmented nevi and multiple tumors (subcutaneous, lipomas, hamartomas). This syndrome belongs to the same group as Recklinghausen disease, Maffucci or Klippel Trenaunay syndromes. The prognosis is not well known but mostly depends on functional and psychologic consequences of important deformations. PMID- 2206107 TI - [Echography of the hip in the infant: 10 years later]. PMID- 2206108 TI - [The choice between theophylline and caffeine in the treatment of apnea in premature infants]. AB - In a double blind study, two comparable groups (each n = 10) of premature infants less than 34 weeks of gestational age, with idiopathic apnea were given an IV treatment of either theophylline or caffeine. The loading doses were respectively 6 and 10 mg/kg and the maintenance doses were 2 and 1.25 mg/kg every 12 hours. In both groups, apneas greater than or equal to 15 s. with or without bradycardia were similarly reduced (p less than 0.01). Both drugs increased significantly the respiratory rate. Compared to caffeine, theophylline induced a significant acceleration of heart rates, an increase in urinary sodium excretion, more frequent gastrointestinal intolerance and behavioral changes. Plasma concentrations of theophylline were less stable than those of caffeine. These data suggest that a single daily dose of caffeine should be preferentially used in the treatment of idiopathic apneas of prematurity. PMID- 2206109 TI - [The value of microcomputers in the diagnosis of craniofacial dysmorphism with multiple congenital abnormalities in children]. PMID- 2206110 TI - Fibrocartilaginous emboli to the spinal cord: a case report. AB - Fibrocartilaginous emboli to spinal cord vessels are a rare and fatal cause of spinal cord injury. We reviewed the medical literature and discovered only 24 cases reported, all in the last 28 years. For all previously reported patients, onset of initial symptoms to maximal neurologic deficit was from a few minutes to as much as two days. All 24 of these patients died an average of 9.6 weeks post onset (range = three hours to 11 months) due to complications related to their spinal cord injury; in all cases, the pathologic diagnosis was made postmortem. We report a 20-year-old man with high-level quadriplegia and respiratory paralysis due to fibrocartilaginous emboli to spinal cord vessels, which occurred after a minor automobile accident. He was the longest-surviving patient reported with this diagnosis. He died six years and seven months after onset, having been on 24-hour ventilatory support. The pathologic diagnosis was not suspected before his death; it was made during postmortem examination. PMID- 2206111 TI - Effects of CGS 9896 in acute experimental intoxication with fluostigmine. AB - The therapeutic effectiveness of CGS 9896, a novel potent anxiolytic and anticonvulsant, in organophosphate intoxication was studied. It was demonstrated that this drug, used as an adjunct to a mixture of atropine and obidoxime, led to a rise in the LD50 of fluostigmine in mice of more than 150 times and more than 138 times for 2 and 24 h, respectively. After 24 h, this effect was twice that of diazepam, which served as a reference drug. PMID- 2206112 TI - Is it time to measure apolipoprotein B? PMID- 2206114 TI - Noninvasive ultrasound evaluation of pressure gradients in aortic root of homozygotes for familial hypercholesterolemia. AB - The aim of this study was to measure noninvasively by Doppler ultrasound the blood flow velocity at the level of the aortic root in patients with homozygous familial hypercholesterolemia (FH) to detect abnormal pressure gradients. Seven patients with homozygous FH and seven healthy controls matched for age and sex were included in the study. Continuous-wave Doppler (2 MHz) was used to measure the highest detectable velocity from the aortic root; the probe was positioned in the suprasternal notch. When an abnormal velocity was detected, the corresponding pressure drop was calculated from the formula: Delta P = 4Vmax2. Each FH patient had an abnormal aortic velocity consistent with a pressure gradient across the valvular area. All the controls had normal aortic velocities (p less than 0.01). The measurement of the pressure drop across the aortic valvular area in FH patients gives an estimate of the lesions produced by cholesterol deposition in a crucial area of the cardiovascular system near the origin of coronary arteries. The noninvasivity of this method makes it an excellent method for obtaining parameters for follow-up and clinical trials. PMID- 2206113 TI - Does measurement of apolipoprotein B have a place in cholesterol management? PMID- 2206115 TI - Management of insulin dependent diabetes. AB - Modern management of patients with insulin-dependent diabetes mellitus (IDDM) is a specialised area, usually undertaken as a team effort by general practitioner, diabetes specialist, diabetes educator and dietitian. Treatment includes that of associated problems, early intervention and management of foot problems and of sick days. PMID- 2206116 TI - The patient with newly diagnosed diabetes mellitus. AB - This outline is based on dietary advice, regular exercise, diabetes education (including glucose monitoring) and, if necessary, an oral hypoglycaemic agent or insulin. Precipitating factors such as dietary indiscretions, infections, drugs, thyrotoxicosis and haemochromatosis should be sought, and associated cardiovascular risk factors such as obesity, hyperlipidaemia, hypertension and a history of smoking should receive attention. PMID- 2206117 TI - Dr James Harrison Leavesley. General practitioner, medical historian, author and radio personality. PMID- 2206119 TI - Psychosocial and physical activity changes after gastric restrictive procedures for morbid obesity. AB - Gastric restrictive procedures for morbid obesity are frequently performed to reduce problems arising from the physical limitations and social isolation of massive obesity. Numerous reports have described changes in weight after gastric restrictive operations, yet few studies have documented changes in the secondary effects of obesity. This report deals with changes in psychosocial status and physical activity occurring in 240 patients who remained in the study 3 years after surgery. These patients were members of a group of 310 patients who were entered into a prospective randomized trial to assess the relative benefits of three forms of gastric restrictive procedure. Prior to operation, and at yearly intervals after operation, the physical activities and psychosocial status of each patient was assessed by a standardized semi-structured interview. At the time of the three-year interview the median weight loss for these patients was 29.5 kg which represents 53% of excess weight lost. This weight loss was associated with a marked reduction in the amount of food eaten. There was a significant increase in the number of patients smoking more than 20 cigarettes a day and a mild increase in alcohol intake. There were significant improvements in the level of self-image and state of happiness. The social lives and sex lives of the majority of patients were improved and a significantly greater number of patients reported being in a stable emotional relationship at 3 years after operation than did so pre-operatively. There was a marked increase in the number of patients in full-time or part-time employment from 38% prior to surgery to 60% at 3 years after operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206118 TI - Blood vessel structure and function: a brief update on recent advances. AB - This article briefly reviews recent advances in knowledge of the histology and function of blood vessels. It focuses upon the multifunctional roles of endothelium and smooth muscle cells. Particular reference is made to the synthesis of a number of factors now known to be involved in maintenance of the integrity of the vessel wall and the initiation of arterial disease. The cells of the vascular wall are much more versatile and dynamic than previously thought. PMID- 2206120 TI - Mathieu urethroplasty with preputial reconstruction and urethral stent urine drainage. AB - Foreskin reconstruction and urethral stent urine drainage were used successfully in 17 Mathieu urethroplasties. No significant complications occurred. The techniques and their advantages are outlined. PMID- 2206121 TI - Liver surgery: the past 2000 years. AB - Liver surgery has grown over 2000 years from the mystic hepatoscopy of the Babylonians to the ultimate of orthotopic transplantation by Starzl in 1968. The first successful liver resection was for trauma by Hildanus in the 17th century. The first successful planned resection was by Langenbuch in 1888 and the first hemihepatectomy by Wendel in 1911. The principles of liver regeneration and liver haemostasis were determined in the period 1880-1900: Ponfick, Mayer, Kousnetzoff, Pensky and Pringle made significant contributions. Couinaud and Healey and Schroy popularized segmental anatomy: Lortat-Jacob and Robert performed the first inflow ligation resection and started the modern era. Starzl brought liver transplantation to its current status and Bismuth introduced hepatobiliary units as a means of optimizing treatment of liver disease. PMID- 2206122 TI - Mazabraud's syndrome: intramuscular myxoma associated with fibrous dysplasia of bone. AB - A 53 year old male with a large swelling on the medial aspect of his right thigh was referred with a presumptive diagnosis of soft tissue sarcoma. However, biopsy revealed intramuscular myxoma and X-rays and CT scans suggested fibrous dysplasia of adjacent bone. Angiography had shown an expanded, hypervascular, intramedullary lesion in the femur, and a large avascular soft tissue mass lying medially in the distal thigh. Fibrous dysplasia of the femur was confirmed on bone biopsy. Subsequently one large and two smaller intramuscular myxomata were excised, with an uneventful postoperative course. This case illustrates Mazabraud's syndrome: the rare association between benign intramuscular myxoma and fibrous dysplasia of bone. PMID- 2206123 TI - [Pain and suffering in animals]. AB - The perception of pain stimuli by nociceptors and their conduction to the diencephalon are approximately identical processes in higher animals and in man. There are however differences between man and animal as well as between the species of animals concerning mental processing and assessing of pain. The importance of fear must be taken into regard. At the moment a scientific assessment of pain and suffering in animals is not possible. PMID- 2206124 TI - [Comparative studies of the detection of Corynebacterium suis infections in swine by indirect immunofluorescence and culture]. AB - In a comparative study 47 urine samples of sows and 9 swabs of preputial diverticulum of boars were investigated for detection of Corynebacterium suis (Eubacterium suis) using an indirect immunofluorescent technique, a Gram stained preparation, a direct culture technique and a culture technique after enrichment. Examinations show that the indirect immunofluorescent technique and the enriched culture technique provide the best results, but that the fluorescent technique saves time and expenses. Additionally in contrast to culture techniques the detection of C. suis is not affected by accompanying bacteria. Using an indirect immunofluorescence it is possible to detect antibody-coating of C. suis in urine sediment of sows as well. There were close correlations between evidence of antibody-coated C. suis and the presence of an ascending pyelonephritis. PMID- 2206125 TI - [Peculiarities of pharmacokinetics in young animals]. AB - In young animals, especially in newborns, absorption, distribution, metabolism and elimination of drugs differ markedly from adults. Respective differences and the cause of these differences are described, including some examples of drug pharmacokinetics in young and adult animals of different species. However, the estimation of pharmacokinetic differences and their pharmacological consequences in young animals is not generally possible, because published data on characteristics of pharmacokinetics in young animals are available only for relatively few drugs. Furthermore, such estimation is complicated by an interaction of different pharmacokinetic processes. Thus, a generally accepted adaptation of dosage schedules for drugs in young animals cannot be offered as yet. In any event, veterinarians should consider the age-dependency of drug pharmacokinetics when drugs, dosages and dosage intervals for treatment of young animals are chosen. PMID- 2206126 TI - Mapping and sequencing in two intron regions of the human dystrophin gene. PMID- 2206127 TI - [Affinity chromatography of proteases using peptide methyl ketones as ligands]. AB - Peptide methyl ketones acting as reversible inhibitors of serine and cysteine proteases were introduced as a new type of ligands in the affinity chromatography. Subtilisins and related serine proteases with an inhibition constant to the soluble inhibitor Z-Ala2-PheCH3 of less or equal than 3 x 10(-5) M are nearly completely adsorbed by the affinity gel Sepharose 4B-epsilon aminocaproic acid-Ala2-PheCH3. The well-known cysteine protease papain binds also to this gel. The elution of the enzymes could be performed by means of iso propanol. Thermitase purified with this method is, regarding to its quality, comparable with enzyme preparations using isoelectric focusing and adsorption at porous glass bodies, respectively. PMID- 2206128 TI - Disparate regulation of interleukin 8 gene expression from blood monocytes, endothelial cells, and fibroblasts by interleukin 4. AB - The role(s) of novel chemotactic cytokines as mediators in the pathogenesis of many acute and chronic disease states is becoming increasingly apparent. One of these cytokines, interleukin 8, is a product of both immune and non-immune cells. In this manuscript, we describe the suppression of IL-8 gene expression from stimulated monocytes by IL-4, while IL-4 had no suppressive effects on IL-8 gene expression from stimulated fibroblasts and endothelial cells. Our data suggest that IL-4 may function as an endogenous regulator of monocyte cytokine expression, including the chemotactic cytokine IL-8. PMID- 2206129 TI - Structure and fluctuations of bacteriophage T4 glutaredoxin modelled by molecular dynamics. AB - A 120 ps molecular dynamics (MD) trajectory for bacteriophage T4 glutaredoxin was calculated including non-inertial solvent effects. The potential energy attains an equilibrated regime after the first 20 ps. The r.m.s. difference of all non hydrogen atoms between X-ray and average MD structures for the regular secondary structure is 0.99A which shows that the MD simulation reproduces the essentials of the structure with high accuracy. Loop displacements are detected, shown by the larger full structure all non-hydrogen atom r.m.s. difference of 1.2A. The fluctuation pattern derived from MD agrees fairly well with that derived from X ray isotropic temperature factors. The active site is a stable structural region in this MD modellization. Structural changes are put in context with the protein's function. PMID- 2206130 TI - Phosphoramidon, a metalloproteinase inhibitor, suppresses the secretion of endothelin-1 from cultured endothelial cells by inhibiting a big endothelin-1 converting enzyme. AB - Time-dependent secretion of immunoreactive-endothelin (IR-ET) from cultured porcine aortic endothelial cells was markedly suppressed by phosphoramidon is due to proteinase inhibitor. Analysis of the culture supernatant with or without phosphoramidon by reverse-phase high performance liquid chromatography confirmed that the suppression of IR-ET secretion by phosphoramidon is due to a decreae in secretion of endothelin-1-like materials. The secretion of the C-terminal fragment (CTF, 22-39)-like materials of big ET-1 was also decreased by phosphoramidon, whereas there was an increased secretion of big ET-1-like materials. These data strongly suggest that phosphoramidon suppresses the secretion of ET-1 from cultured endothelial cells by inhibiting the conversion of big ET-1 to ET-1. It is most likely that phosphoramidon-sensitive metalloproteinase is responsible for the processing of big ET-1 in vascular endothelial cells. PMID- 2206131 TI - Chemo-enzymatic synthesis of optically pure l-leucovorin, an augmentor of 5 fluorouracil cytotoxicity against cancer. AB - Optically pure l-leucovorin was synthesized on a large scale by the combination of chemical and enzymatic processes. After reduction of folate with zinc, dihydrofolate was reduced asymmetrically to (6)-tetra-hydrofolate by use of dihydrofolate reductase from E. coli C600/pTP600, with simultaneous NADPH cofactor recycling using glucose dehydrogenase from Gluconobacter scleroideus KY3613. Calcium l-leucovorin.4H2O (113 g) was obtained from (6S)-tetrahydrofolate via 5,10-methyenyltetrahydrofolate by formylation, reflux, addition of calcium ions and floricil column chromatography, with an overall yield of 50% based on folate. The l-leucovorin showed optical purity of 99.9% de as (6S)-form. PMID- 2206132 TI - Role of protein kinase C in the regulation of glucagon gene expression by arginine. AB - The cellular mechanism of glucagon gene expression in intact rat islets and their synthesis and release of glucagon were investigated. Arginine significantly increased the amounts of preproglucagon mRNA and glucagon in the islets and glucagon release. H-7, a specific inhibitor of protein kinase C (PKC), significantly inhibited these effects of arginine. However, H-8, a potent inhibitor of cyclic nucleotide-dependent protein kinases, did not affect the arginine-induced biosynthesis of glucagon or glucagon release. These results suggest that the regulation of glucagon gene expression by arginine is mediated by PKC, not by cyclic nucleotide-dependent protein kinases. PMID- 2206133 TI - Protein factor obtained from rat adipose tissue specifically permits the proliferation of the 3T3-L1 and Ob1771 cell lines. AB - We have found the presence of protein factor in rat adipose tissue which permits the proliferation of 3T3-L1 and Ob1771 preadipocytes cultured in a completely defined serum-free medium containing only progression factors [epidermal growth factor (EGF) and insulin] as growth factors. This mitogenic activity of the protein factor was not detected in various other cell lines, in particular, Swiss 3T3 cells which could proliferate in response to a competent factor [platelet derived growth factor (PDGF) or fibroblast growth factor (FGF)] in the same serum free medium. This activity of the factor was heat- and pronase-unstable, and reductant-stable, and the apparent molecular weight of the factor was about 20,000. These results strongly suggest that the protein factor is different from PDGF or FGF and contributes to the formation of new adipocytes by specifically stimulating the proliferation of preadipocytes, acting like competent factor. PMID- 2206134 TI - Proton magnetic resonance study of cycloheximide-ribosome interactions. AB - Cycloheximide-ribosome interactions from sensitive and resistant organisms were studied by proton magnetic resonance spectroscopic techniques. The two methyl resonances of cycloheximide upon interaction with ribosomes from Saccharomyces cerevisiae showed preferential broadening. Comparison of cycloheximide line broadening as effected by ribosomes from S. cerevisiae (sensitive) and Microsporum canis (resistant) revealed that less cycloheximide is bound to the M. canis ribosomes. From the decrease in line broadening observed with increasing temperature it may be concluded that cycloheximide-ribosome interaction is a fast exchange reaction. Tetracycline did not compete with cycloheximide for binding site(s) on the ribosomes of S. cerevisiae. PMID- 2206135 TI - Sequence studies of rabbit serum transferrin. AB - Large fragments of rabbit serum transferrin have been prepared by enzymatic digestion with subtilisin and by chemical cleavage with BNPS-skatole. Sequence determinations on fragments from the N-terminal lobe lead to the assignment of 273 residues and those from the C-terminal lobe 267 residues. Together with previous determinations, a total of 614 of the ca 679 residues in rabbit transferrin have been assigned. A number of corrections are made to the preliminary sequence assignments of O.U. Beg, H.A. McKenzie and D.C. Shaw (1988) Biochemistry International 17, 1135-1142. PMID- 2206136 TI - Rat brain insulin degrading enzyme in insulin and thyroid hormones imbalances. AB - Rat brain insulin degrading enzyme activity and its relationship with insulin receptor were investigated in experimental hyperglycemia, hyperinsulinemia, hypothyroidism and hyperthyroidism. Insulin degrading enzyme activity was assessed in synaptosomes and high speed cytosol using [125I]insulin. Levels of insulin degrading enzyme were changed in high speed cytosol in insulin and thyroid hormone imbalances. These results suggest that insulin degrading enzyme in brain is predominantly active in cytosol and is subject to regulation by insulin and thyroid hormones. Probably it plays some role in long term effects of insulin in brain. PMID- 2206137 TI - Hormone regulated enzyme activities of plasma membrane of decidual endometrium of the rat. AB - Plasma membranes were purified from deciduoma of pseudopregnant rats and rat liver. Preparations contained 80% plasma membrane-derived material as based on electron microscope morphometry and analysis of enzyme markers. Several plasma membrane enzymes were tested for direct response to hormones. NADH-ferricyanide reductase of plasma membranes from both tissues was stimulated by glucagon and inhibited by insulin but was unresponsive to steroids. For steroids, responsiveness was limited to a reduction in NaF-stimulated adenylate cyclase activity by the steroid R5020. Thus, interaction of steroid hormones with plasma membranes, unlike that of glucagon and insulin, is not reflected in an altered activity of plasma membrane-bound dehydrogenases but may be exerted directly on adenylate cyclase. PMID- 2206138 TI - Effect of inhibition of glutathione synthesis on the immunogenicity of captopril and captopril-protein conjugates in the mouse. AB - The effect of glutathione (GSH) depletion on the immunogenicity of captopril (CP) and D-penicillamine (PA) was investigated in C57 mouse. Depletion of GSH was by DL-buthionine sulfoximine (BSO), a potent and specific inhibitor of GSH synthesis, injected on the days of immunization of the drug/drug-protein conjugates. Chronic BSO pretreatment for 5 consecutive days, before and including the 4-day immunization period, caused tissue GSH depletion (liver 60%, kidney 71%, lung 14%, spleen 14% and whole blood 36%) in C57 mouse. After chronic administration of CP (270 mumol/kg, i.p. or i.m.) or CP-HSA (200 micrograms, i.p. or i.m.), IgG antibody response to CP-derived antigen was detected by an enzyme linked immunosorbent assay (ELISA). The IgG antibody recognised CP-OVA but not OVA, and was inhibited by CP in other protein conjugated form, thus confirming its specificity to CP. Depletion of GSH by BSO caused an increase in the CP specific IgG antibody titre when CP/CP-HSA was immunized through i.p. (with or without Freund's Complete Adjuvant) but not i.m. administration. In contrast, chronic administration of PA (270 mumol/kg, i.p.) or PA-HSA (200 micrograms, i.p.), with or without BSO pre-treatment, did not lead to detectable PA-specific IgG antibody. The results again illustrate the difference in the intrinsic immunogenicity between CP and PA, in that depletion of GSH increased the humoral (B lymphocyte) anti-CP responses but not anti-PA responses under the experimental conditions. These findings suggest that GSH status, apart from its effects on the disposition of CP/CP-protein conjugates, should be considered as an important determinant of both the immunological and toxicological response to CP. PMID- 2206139 TI - Kinetics and mechanism of uptake of platinum-based pharmaceuticals by the rat small intestine. AB - The absorption of two platinum-based pharmaceuticals, cisplatin and carboplatin, was studied using in vitro and in situ models. By utilizing everted rat small intestine, it was found that absorption of both drugs was linear with time up to 60 min and was not saturable up to a concentration of 1.0 mM. Moreover, uptake against a concentration gradient could not be demonstrated and absorption was not reduced by metabolic inhibition or anoxic conditions. These results indicate the lack of involvement of an active transport mechanism for cisplatin and carboplatin and imply that absorption across the gastrointestinal tract is by passive diffusion. Cisplatin was absorbed more readily than carboplatin, both in vitro and in situ. In situ both drugs were found to disappear from the intestinal lumen following first-order kinetics. The results of in situ studies indicate that a decrease in pH of the perfusion medium leads to an increase in absorption of carboplatin into the systemic blood. This report establishes the fact that both cisplatin and carboplatin are absorbed across the gastro-intestinal tract and indicates that preclinical trials involving oral administration of platinum based pharmaceuticals could be justified. PMID- 2206141 TI - Evaluation of women with possible appendicitis using technetium-99m leukocyte scan. AB - The authors evaluated the use of technetium-99m albumin colloid white blood cell (TAC-WBC) scan in women with possible appendicitis. One hundred and nine women underwent 110 TAC-WBC scans. One woman had a second scan on a separate admission and was considered two individual patients in the analysis. Twenty-six women had appendicitis, 10 of whom had a perforated appendix at surgery. The TAC-WBC scan was indeterminate (abnormal but nondiagnostic for appendicitis) in 52 women (47%), nine of whom had appendicitis. Fifty-eight scans were read as positive or negative for appendiceal pathology. There were 16 true positives, 5 false positives, 36 true negatives, and 1 false negative. The predictive value of a positive scan was 76%, and the predictive value of a negative scan was 97%. The TAC-WBC scan was positive in 62% of patients with appendicitis and negative in 43% of the patients without appendicitis resulting in an overall accuracy of 47% in the 109 women. The main value of TAC-WBC scan in women with possible appendicitis is its high negative predictive value and the main problem with the TAC-WBC scan is its high indeterminate rate. PMID- 2206140 TI - Vitamin E status during dietary fish oil supplementation in rheumatoid arthritis. AB - The primary objective of this study was to determine whether it is the fish oil itself or the alpha-tocopherol that is added to the fish oil preparations (to prevent peroxidation) that is responsible for the beneficial effects of dietary supplementation with fish oil in patients with rheumatoid arthritis (RA). One group of RA patients took fish oil supplements and another group took alpha tocopherol-enriched coconut oil supplements (placebo controls), both for 3 months. Clinical and laboratory indices of RA activity in relation to cellular and plasma vitamin E levels were assessed at the beginning and the end of the trial. The results of the study provide evidence that the beneficial effects of fish oil supplementation cannot be ascribed to the antioxidizing properties of the alpha-tocopherol per se. PMID- 2206142 TI - Cause of death in an emergency department. AB - A retrospective review was done of 601 consecutive emergency department deaths. Nontrauma causes accounted for 77% of the deaths and this group had an average age of 64 years and a male to female ratio of 1.9:1. Trauma caused 23% of the fatalities and this group had a younger average age of 29 years and a male to female ratio of 4.6:1. The most common causes of nontrauma death were sudden death of uncertain cause (34%), coronary artery disease (34%), cancer (5%), other heart disease (4%), chronic obstructive lung disease (3%), drug overdose (3%), and sudden infant death syndrome (2%). The most common causes of trauma death were motor vehicle accidents (61%) and gunshot wounds (16%). The overall autopsy rate was 40%. Death certificates were often in error. PMID- 2206143 TI - Treatment of Fournier's gangrene with adjunctive hyperbaric oxygen therapy. AB - Fournier's gangrene is a devastating infection and often is associated with a high morbidity and mortality. Surgical debridement and antibiotics are the cornerstones of therapy. This case describes the use of hyperbaric oxygen as an adjunct in the treatment of Fournier's gangrene. PMID- 2206144 TI - Intermittent obstruction of an incarcerated hiatal hernia with a total thoracic stomach. AB - A case of intermittent obstruction of a sliding hiatal hernia is presented. The obstruction occurred when the patient's stomach was totally above the diaphragm. The anatomy of sliding hiatal hernias is discussed, as well as the presenting signs and symptoms of obstruction in sliding hiatal hernias. PMID- 2206145 TI - Cases in electrocardiography. PMID- 2206146 TI - 1989 annual report of the American Association of Poison Control Centers National Data Collection System. PMID- 2206147 TI - Ultrasonography in Japanese emergency departments. AB - This is a review of 50 consecutive cases where ultrasound was performed in the emergency department of a general hospital demonstrating the efficacy of its usage by "nonspecialists." This study demonstrates that in the Japanese model of emergency care delivery, abdominal ultrasound has been shown to be used in the emergency department with accuracy and safety. PMID- 2206148 TI - Trauma: an annotated bibliography of the recent literature. PMID- 2206149 TI - Bilateral spontaneous pneumothorax after cocaine inhalation. PMID- 2206150 TI - Pressure necrosis following ethchlorvynol overdose. PMID- 2206151 TI - Mismanagement of a potential cervical spine injury. PMID- 2206152 TI - Emergency department sonography by emergency physicians. PMID- 2206153 TI - Compartment syndrome with resultant amputation following intraosseous infusion. PMID- 2206154 TI - Ineffectiveness of oral labetalol for hypertensive urgency. PMID- 2206155 TI - Periventricular hyperintensity detected by magnetic resonance imaging in infancy. AB - Twenty-one infants younger than 12 months of age were diagnosed as having periventricular hyperintensity (PVH) on T2-weighted magnetic resonance imaging. Ten infants had experienced neonatal asphyxia, 6 intracranial hemorrhage, 2 bacterial meningitis, and 3 apnea. PVH was classified according to its extent. Round foci of PVH surrounding the frontal and occipital horns of the lateral ventricles were observed in 4 infants (PVH pattern I). Continuous PVH was observed in 17 infants (PVH patterns II and III). Fourteen infants with continuous PVH had spastic diplegia or quadriplegia. Developmental delay was demonstrated in 15 infants with continuous PVH. No PVH pattern I infants had cerebral palsy; only 1 such infant had mild developmental delay. Our study suggests that the extent of PVH reflects the severity of brain damage in neonates with cerebral injuries. PMID- 2206156 TI - Anencephaly: clinical determination of brain death and neuropathologic studies. AB - Twelve liveborn anencephalic infants were serially examined to determine if they would meet our clinical criteria for whole brain death within a 7-day period: Protocol 1 infants (6) received intensive care including intubation from birth; and Protocol 2 infants (6) received intensive care during the period in which death was imminent. Brain death was determined by absence of brainstem function, including loss of all cranial nerve responses and sustained apnea (PCO2 greater than 60 torr) for 48 hours with confirmation of findings by an outside consulting child neurologist. The initial examinations of these 12 infants revealed spontaneous movements and startle myoclonus (12), suck, root, and gag responses (7), increased tone (8), deep tendon reflexes (9), absent pupillary responses (9), absent oculocephalic and corneal responses (6), absent auditory/Moro responses (7), and nonvisualization of the optic nerve (8). Mild depression of neurologic function occurred during the first several days of life; subsequently, the infants' responses were easier to elicit and more sustained. Only 2 infants met the clinical criteria for brain death. Neuropathologic findings indicated that observed complex motor responses were not based upon cortical activity because no infant had a normally-formed cerebrum. Brainstem neuronal activity may have accounted for these motor responses in some patients but even at this level neurons were scanty or absent. Our findings suggest that, although rare, clinical brain death can be determined in liveborn anencephalic infants; ophthalmologic and otologic developmental abnormalities may confound examination of cranial nerve function; and absence of cortical neurons supports the widely held opinion that these infants do not experience sensation. PMID- 2206157 TI - Gross motor patterns in children with cerebral palsy and spastic diplegia. AB - Rolling, sitting, and crawling patterns were motoscopically analyzed in 72 children with cerebral palsy and spastic diplegia; the relation between these patterns and the severity of the locomotive disability was studied. In rolling, trunk rotation and elbow support were difficult for the most severely diplegic children. When sitting, most patients had a between-heel sitting pattern in which the thighs were adducted and the knees were flexed. When crawling, the reciprocal thigh movements were insufficient and accompanied by lateral bending of the trunk in many patients. In the more impaired patients, the thighs supported the weight in flexion and did not move reciprocally. Creeping on the elbows without reciprocal leg movements was demonstrated in the most severely affected children after 2 years of age. PMID- 2206158 TI - Haemophilus influenzae meningitis with prolonged hospital course. AB - A retrospective evaluation of Haemophilus influenzae type b meningitis observed over a 2-year period documented 86 cases. Eight of these patients demonstrated an unusual clinical course characterized by persistent fever (duration: greater than 10 days), cerebrospinal fluid pleocytosis, profound meningeal enhancement on computed tomography, significant morbidity, and a prolonged hospital course. The mean age of these 8 patients was 6 months, in contrast to a mean age of 14 months for the entire group. Two patients had clinical evidence of relapse. Four of the 8 patients tested for latex particle agglutination in the cerebrospinal fluid remained positive after 10 days. All patients received antimicrobial therapy until they were afebrile for a minimum of 5 days. Subsequent neurologic examination revealed a persistent seizure disorder in 5 patients (62.5%), moderate-to-profound hearing loss in 2 (25%), mild ataxia in 1 (12.5%), and developmental delay with hydrocephalus which required shunting in 1 (12.5%). One patient had no sequelae. PMID- 2206159 TI - Dystrophin analysis in the differential diagnosis of autosomal recessive muscular dystrophy of childhood and Duchenne muscular dystrophy. AB - We report 2 patients with childhood autosomal recessive muscular dystrophy. Both patients had slight muscle weakness without enlargement of the calf muscles or involvement of the facial muscles. Their clinical courses are static. Muscle histology revealed characteristic features of muscular dystrophy. Dystrophin was identifiable in the sarcolemma of both patients by immunocytochemical staining with an antidystrophin antibody. At an early age, immunocytochemical analysis with antidystrophin antibody was useful in distinguishing between childhood autosomal recessive and Duchenne muscular dystrophies. PMID- 2206160 TI - EEG correlation of improvement in hemolytic-uremic syndrome after plasma infusion. AB - We report a previously undescribed electroencephalographic pattern of epochs of diffuse delta background (85-240 sec) alternating with epochs of classic "burst suppression" (90-270 sec) in a 13-month-old girl with hemolytic-uremic syndrome. A dramatic electroencephalographic improvement was evident on continuous monitoring of cerebral function 3 hours after initiating fresh frozen plasma infusion, well before any clinical improvement was apparent. This patient, in addition to the unusual electroencephalographic findings, illustrates the role of continuous electrophysiologic monitoring of cerebral function and supports the use of fresh frozen plasma in hemolytic-uremic syndrome. PMID- 2206161 TI - Cerebellopontine angle lipoma in a teenager. AB - Lipomas of the cerebellopontine angle are very rare lesions. To date, 18 patients have been reported, 17 of whom were adults. A second child is described with cerebellopontine angle lipoma. PMID- 2206162 TI - Reversible myopathy due to labetalol. AB - A severe, generalized myopathy developed in 2 children treated with labetalol. An 11-year-old girl and a 14-year-old boy demonstrated proximal weakness and markedly elevated creatine kinase levels during labetalol therapy. Clinical improvement began immediately when labetalol administration was halted; muscle strength was normal within 2 months. Muscle biopsies were consistent with rhabdomyolysis. PMID- 2206163 TI - Factor XIII deficiency and intracranial hemorrhages in infancy. AB - We report an infant with Factor XIII deficiency who had 2 seemingly spontaneous intracranial hemorrhages. It is important to consider Factor XIII deficiency as a possible cause of unexplained intracranial hemorrhages in infancy. Ongoing factor replacement therapy is recommended to prevent further bleeding episodes. PMID- 2206165 TI - Medulloblastoma cell line. PMID- 2206164 TI - Varicella with delayed hemiplegia. AB - We report 4 children who developed acute hemiplegia 7 weeks to 4 months after varicella infection. In 2 patients, carotid angiography demonstrated segmental narrowing and occlusion of the middle cerebral artery. Their clinical and angiographic features were similar to those associated with contralateral hemiplegia after herpes zoster ophthalmicus, the pathogenesis of which comprises cerebral angiitis due to varicella zoster viral infection. We believe that our patients had the same pathogenesis. In a survey of infectious diseases in our region, the frequency of varicella with delayed hemiparesis was roughly 1:6,500 varicella patients. PMID- 2206166 TI - Infantile MS and Schilder disease. PMID- 2206167 TI - [Transfusion of concentrates enriched in neocytes in the thalassemic child. Preliminary results]. AB - In this study, we compared the results of young red cells transfusion for 12 months with the administration of conventional red cells units during the year before, in three thalassemic children. We used the Neocel system (Cutter laboratories) to prepare neocytes. A quality control of neocyte units was developed: especially the phthalate oil technique which shows a 70% enrichment of young red cells. These patients received 170.4 +/- 9 ml/kg of body weight of neocytes compared with 197 +/- 20 ml/kg of body weight of conventional red cells concentrates. The mean decrease of hemoglobin transfused per kg of body weight per year was 22%. The mean pretransfusion hemoglobin level did not change during the 2 years of study. The children grow without any problem and no pathologic event occurred during the study. The control of the serological ferritin levels does not allow for definitive conclusions in the evolution of the iron overload of our three patients. However, this overload seems to decrease. It's why it's necessary to carry on with our study. PMID- 2206169 TI - [Epidemiologic study of HIV serology among blood donors in the north-eastern region of France]. PMID- 2206168 TI - [New methods of interlaboratory monitoring of HIV-1 ELISA kits. Comparative study of 2 periods: 1/12/1988 to 15/4/1989 and 15/4/1989 to 31/8/1989. Le Groupe Retrovirus de la Societe Nationale de Transfusion Sanguine]. AB - Since december 1st 1988, the Retrovirus study Group of the French Society of Blood Transfusion has initiated a systematic multicentric control of all anti-HIV screening EIA test kits lots used by each member of the group. For this purpose a special panel (GRV) has been designed and forwarded to each laboratory. From december 1st 1988 to august 8 1989, 6 HIV-1 kits have been in use (Diagnostics Pasteur Elavia 1; Diagnostics Pasteur Rapid'Elavia; Organon Vironostika; Abbott HIV recombinant; Du Pont env 9; Wellcome Wellcozyme). The GRV panel has been run 204 times on 102 different lots in 12 laboratories. Results after 9 months show that these 6 kits almost always properly recognize the 5 HIV 1 positive samples of the panel. However they differ in their ability to recognize HIV 2 positive samples. Variations in results are observed from lot to lot as well as between the first half of this period and the second. PMID- 2206170 TI - [Evidence of post-transfusional hepatitis B from the viral DNA]. PMID- 2206171 TI - Avoidable deaths in Greenland 1968-1985: variations by region and period. AB - The concept of avoidable deaths suggests that certain deaths ought not occur in a given society because it is possible to prevent or treat the disease or condition. A list of avoidable deaths is time and community specific as it reflects the socioeconomic conditions, professional medical capacity and political will of the society. A list of avoidable deaths is proposed for Greenland which includes, inter alia, meningitis, lung cancer, acute respiratory infections, suicides, boat accidents and alcohol related diseases and accidents. All were considerably more common in Greenland than in Denmark and several showed an increasing time trend. The regional patterns were particularly clear for infectious diseases and accidents, which showed low mortality rates in the capital and other towns and high mortality rates in settlements and in the remote East Greenland, while mortality rates from suicides and alcohol related diseases were high in the capital and East Greenland and low in West Greenlandic settlements. It is concluded that further studies on preventable diseases and causes of death, in particular certain infectious diseases, accidents and suicides, are needed. PMID- 2206173 TI - Fatal accidents in Greenland. AB - The occurrence of fatal accidents in Greenland was studied for 1968-1985 with emphasis on the native Inuit population. 1004 deaths were recorded, 43% of which were drowning and boat accidents. The mortality rates from all fatal accidents together were 202 and 72 per 100,000 person-years in males and females, respectively, and fatal accidents made up 16% of all deaths. 23% of the accidents were alcohol related, considerably more in certain age groups and in females. Most accident types, including alcohol related accidents, showed a decreasing mortality trend during the period of study but boat accidents not related to alcohol increased significantly. The mortality rates were higher in East Greenland than in West Greenland for most accident types and, in West Greenland, the mortality rates from drowning, boat accidents, fire and accidental shots increased with remoteness from the capital. Many accidents can be prevented but certain accidents are natural consequences of traditional activities which hold compensating benefits. PMID- 2206172 TI - Episodes of illness and medical service in a geographically isolated mine village in Greenland. AB - A study of all episodes of medical contact in a one year period was performed. 19% of the episodes required sick leave. In all groups the employees single contact due to obligatory medical certificates in case of absence were prevalent. Persons with a seniority of more than five years had about 50% more medical contacts. The threshold for medical contact in Greenlanders was lower probably due to a higher number of women and to the acculturative stress. A higher frequency of episodes of illness among leading managers and other executives in the top of the hierarchy and absence of occupational diseases and injuries were characteristic of this group of employees. PMID- 2206174 TI - Acculturation and adaptation: health consequences of culture contact among circumpolar peoples. AB - An overview is presented of the processes of acculturation and adaptation. Research with a variety of acculturating groups (including Refugees, Immigrants, Sojourners, Native Peoples and Ethnic Groups) shows that satisfactory adaptations are possible given appropriate conditions in the host or settlement countries. These conditions are largely under the potential control of policy makers and programm developers, and hence healthy outcomes are within reach. When these findings and conclusions are applied to Native Peoples in Circumpolar regions, some particular experiences stand out, resulting in the potential for difficult social and psychological adaptations. However, the literature shows that like all other acculturating groups, successful adaptations are possible for Circumpolar peoples, especially when they are in a position to understand and control the process. PMID- 2206175 TI - Atherosclerosis in native Greenlanders. An ultrasonographic investigation. AB - A low frequency of ischemic heart disease in Eskimos (Inuit) has been regarded as an expression of absent or low atherosclerosis. The true extent of atherosclerosis in the Eskimo populations of the World is not known due to low autopsy activity. In order to register atherosclerotic changes in the carotid and femoral arteries 61 Native Greenlanders from two settlements with a traditional Eskimo life style in the Uummannaq district of Northwestern Greenland were examined ultrasonographically with a portable scanner (Aloka) using a 7.5 MHz 4 cm linear array transducer. The results obtained were compared to an age and sex matched urban control group of 122 Danes from Copenhagen. The investigation showed that the Native Greenlanders had almost the same degree and extent of atherosclerosis in the carotid and femoral arteries as the Danes. Thus, the low incidence of ischemic heart disease in Native Greenlanders may not be attributed to lesser atherosclerosis. Further studies, particularly autopsy studies are needed. PMID- 2206176 TI - Medical aspects of Arctic exploration. 10. Floating down the River of Disappointment: Alexander Mackenzie (1789). PMID- 2206177 TI - AIDS and other sexually transmitted diseases in the Arctic regions. PMID- 2206178 TI - What, if any, are the indications for arthroscopic debridement of the osteoarthritic knee? PMID- 2206179 TI - Cyclops syndrome: loss of extension following intra-articular anterior cruciate ligament reconstruction. AB - Arthrofibrosis is one of the recognized complications following traditional anterior cruciate ligament (ACL) reconstruction. With the advent of arthroscopic assisted ACL reconstructions, the extent of potential arthrofibrosis appeared to be less. However, 13 patients after intra-articular ACL reconstruction using a patella tendon autograft developed a similar symptom complex. In addition to postoperative loss of full extension, there was an audible and palpable clunk with terminal extension. These patients had similar arthroscopic findings of a nodule that formed anterolateral to the tibial tunnel placement of the graft. The arthroscopic appearance of the soft tissue mass with its surface vessels was reminiscent of a "cyclops." After arthroscopy with debridement and manipulation of the knee, extension was improved in all cases. The average range of motion immediately after the procedure was 6.0-130 degrees, compared with 16-103 degrees preoperatively. The range of motion at last follow-up averaged 3.8 degrees of extension and 138 degrees of flexion. All patients had greater than 130 degrees of flexion. There were no complications attributed to the manipulation and arthroscopic lysis of adhesions, and no patient experienced loss of graft integrity or knee stability. The "cyclops" nodule was examined grossly and microscopically and demonstrated peripheral fibrous tissue with a central region of granulation tissue in all specimens. In addition, two specimens were noted to include bony fragments and three specimens contained cartilaginous tissue. PMID- 2206180 TI - Osteochondritis dissecans of the knee: arthroscopic compression screw fixation. AB - This article describes repair of osteochondritis dissecans of the knee by arthroscopic compression screw fixation and reports the healing response and clinical result. Diagnostic and operative arthroscopy was performed. Compression screw fixation was used. The exact operative technique varied depending on the status of the lesion. The patients were non-weight bearing for 2 months, after which a second surgery was necessary for removal of the metallic screw(s). The initial healing response was assessed by the firmness of the lesion to palpation at the second look. Subsequent x-ray evidence of healing was correlated with the clinical outcome. Ninety-four percent of the knees were determined to be initially healed at the time of the second look. Four of these apparently solid repairs subsequently loosened and required repeat surgery. Eighty-eight percent of the patients assessed their results as excellent or good after 2 years minimum follow-up. Arthroscopic compression screw fixation is an effective method of repair for mild to moderately severe cases of osteochondritis dissecans. PMID- 2206181 TI - Osteochondritis dissecans of the knee: a historical review of etiology and treatment. AB - Osteochondritis dissecans (OCD) is a common entity in both the juvenile and adult populations, with an incidence of 3 to 6/10,000 in adults. Much of the early literature grouped juvenile and adult osteochondritis dissecans, osteochondral fracture, and accessory ossification into the same category. Conclusions were then drawn on the combined group. Nonetheless, this is a diverse group. This review discusses only OCD. There have been multiple etiological theories of OCD, ranging from trauma to ischemia to accessory centers of ossification and to genetics. It is evident that the true etiology is probably multifactorial. Bone scan, computed tomographic scan, and magnetic resonance imaging advances have enhanced the physician's ability to make the diagnosis of osteochondritis dissecans as well as to stage operative intervention. There is a vast difference between juvenile and adult OCD, as seen in the natural history, prognosis, and treatment options. In general, the juvenile patients have better results overall. The indications for operative intervention for these juvenile patients are a nonhealing attached fragment, fully or partially detached lesions of the articular surface, and loose bodies. Nonoperative treatment in the adult patient has been shown to accelerate degenerative arthritis, which involves all 3 compartments of the knee. Therefore, symptomatic lesions and loose bodies comprise the surgical indications for adult OCD. An understanding of this disease process will help the physician optimize the patient's results. PMID- 2206182 TI - Arthroscopic strain gauge measurement of the normal anterior cruciate ligament. AB - This article describes a new arthroscopic technique to study the anterior cruciate ligament (ACL) in vivo. A Hall effect strain transducer (HEST) is inserted arthroscopically into the anterior medial band (AMB) of the ACL. The strain is calculated from HEST displacement data. This method determines a reference length of the AMB when it becomes taut and load bearing. Data from HEST implantation in five patients with normal ACLs are reported. The HEST was implanted in the AMB with patients under local anesthesia. Strain was calculated during anterior-posterior shear testing and isometric quadriceps contractions at 30 and 90 degrees of knee flexion. The results demonstrate that this technique is safe and reliable. Lachman testing (anterior shear testing at 30 degrees) caused significantly higher strain in comparison to the drawer tests (anterior shear testing at 90 degrees). A significant increase in strain occurred during isometric quadriceps contraction when the knee was flexed at 30 degrees. No significant change in strain was measured, however, during isometric quadriceps contraction at 90 degrees of flexion. These results confirm previous studies showing that the Lachman test is a more sensitive clinical method for evaluating the AMB. They suggest that isometric quadriceps activity at 90 degrees of knee flexion can be prescribed for rehabilitation without risk of increased strain of the AMB. PMID- 2206183 TI - Primary bone grafting following graft procurement for anterior cruciate ligament insufficiency. AB - A technical recommendation of primarily bone grafting the patellar tendon graft site created following harvesting the central third of the free bone-tendon-bone patellar tendon graft for anterior cruciate ligament (ACL) insufficiency is presented. Harvesting a patellar bone-tendon-bone graft produces a stress riser that increases the potential risk of a patellar fracture. Primary bone grafting of the patellar region is recommended as a simple and safe solution, especially if a graft wider than 10-12 mm or deeper than 6 mm is taken. We feel that this will reduce even further the small likelihood of late patellar fracture. Using these principles, we have not had any late patellar fractures in over 135 consecutive ACL reconstructions since July, 1986. PMID- 2206184 TI - The popliteus tendon and its fascicles at the popliteal hiatus: gross anatomy and functional arthroscopic evaluation with and without anterior cruciate ligament deficiency. AB - Gross anatomical dissection of the popliteus muscle, the popliteus tendon and its fascicles, and their relation to the lateral meniscus was carried out in 14 human adult cadaver knees. Videoarthroscopy through an anterolateral portal was then used to assess and document the functional integrity of the popliteus tendon and its fascicles forming the popliteal hiatus in vivo. A control group of cruciate ligament intact knees (n = 107) was compared with an anterior cruciate ligament (ACL)-deficient group (n = 68). The incidence of structural lesions of the popliteus system was 18.7% in the control knees, 95% in 40 acute ACL disruptions, and 85.7% in 28 chronic ACL-deficient knees. Functional arthroscopic evaluation of the popliteus tendon and its fascicles blending into the lateral meniscus was a valuable adjunct in assessing secondary posterolateral restraints in acute and chronic ACL-incompetent knees. PMID- 2206185 TI - Acute hemarthrosis of the knee: indications for diagnostic arthroscopy. AB - The objective of this study was to define the role of early diagnostic knee arthroscopy for patients with an acute knee injury and hemarthrosis. Forty-five patients with an acute knee injury followed by a posttraumatic hemarthrosis during a 1-year period were prospectively reviewed. All patients were evaluated preoperatively followed by examination under anesthesia and arthroscopy of the knee. The majority of patients, 32 (71%), had an anterior cruciate ligament tear. Meniscal tears occurred in 21 patients (47%). Meniscal tears requiring surgery occurred in only 10 of 25 meniscal tears (40%). Seven patients (16%) had medial collateral ligament and/or posteromedial capsular sprain. Eight patients (18%) had an osteochondral fracture or patellar dislocation associated with an osteochondral fracture. The majority of knees with a torn meniscus or osteochondral fracture had an anterior cruciate ligament tear. Clinically, 18 of 21 knees (86%) with an acute complete anterior cruciate ligament tear were diagnosed preoperatively with the Lachman test. The Lachman test conducted with patients under anesthesia was positive for 19 of 21 knees (90%) with an acute complete anterior cruciate ligament tear. The preoperative examination correctly identified six of seven knees (86%) with a medial collateral ligament sprain. The preoperative Lachman test was positive in only two of five knees (40%) with a partial anterior cruciate ligament tear. The Lachman test with patients under anesthesia was positive for four of five knees (80%) with an acute partial anterior cruciate ligament tear. Preoperative examination yielded the correct diagnosis in only 9 of 21 knees (43%) with a meniscal tear and 1 of 6 knees (17%) with an osteochondral fracture.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206186 TI - Evaluation of patients with persistent symptoms after lateral retinacular release by kinematic magnetic resonance imaging of the patellofemoral joint. AB - The arthroscopic lateral retinacular release is typically performed to treat patellar pain and instability. This procedure was previously considered to be relatively benign with a low associated complication rate. However, a high incidence of medial subluxation of the patella was recently reported in patients with persistent symptoms after lateral retinacular release. Because the use of physical examination criteria may not always be sufficient to assess patellar alignment, 40 patients (43 knees) were evaluated by the newly developed technique of kinematic magnetic resonance imaging of the patellofemoral joint. One (2%) patellofemoral joint had normal patellar alignment, 10 (23%) had lateral subluxation of the patella, 1 (2%) had excessive lateral pressure syndrome, 27 (63%) had medial subluxation of the patella, and 4 (9%) had lateral-to-medial subluxation of the patella. Seventeen of 40 patients (43%) with unilateral arthroscopic lateral retinacular releases had medially subluxated patellae on the unoperated joints. Because patellar malalignment commonly affects bilateral joints, medial subluxation of the patella may have been present before the lateral retinacular release but was not recognized in these patients. PMID- 2206187 TI - Acute pulmonary edema, an unusual complication following arthroscopy: a report of three cases. AB - Acute pulmonary edema in the young athlete is a rare complication following arthroscopic surgery. It is not related to fluid absorption during arthroscopy, but rather to a brief period of upper airway obstruction. Pink, frothy pulmonary edema fluid appears along with other signs of hypoxia. Treatment consists of oxygenation, diuretics, and nitrates. Young athletes may be at increased risk for laryngospasm-induced pulmonary edema because they have the ability to generate large negative intrathoracic pressures. This condition must be recognized promptly to minimize morbidity and mortality. PMID- 2206188 TI - Isolated rupture of the popliteus tendon in a professional athlete. AB - A 24-year-old professional football player sustained an isolated rupture of the popliteus tendon. The injury was confirmed by arthroscopic examination. No clinical instability was present initially or during the recovery period. The injury was managed nonoperatively with the patient able to return to full sports participation. No residual ligament laxity or weakness on isokinetic testing resulted. PMID- 2206189 TI - Our changing needs and conditions: presidential address to the Arthroscopy Association of North America, 1990. PMID- 2206190 TI - Arthroscopy in other countries: presidential guest lecture. PMID- 2206191 TI - Karyometric marker features in fine needle aspirates of follicular adenoma of the thyroid. AB - Karyometric measurements were performed on fine needle aspirates of clearly identifiable adenomatous areas and adjacent normal-appearing areas in the surgical specimens from ten patients with follicular adenomas of the thyroid. Similar measurements were made on aspirates from nine patients free of thyroid disease. A total of 95 karyometric features were evaluated for each nucleus. Analysis of variance of optical density values did not show a significant difference between the three types of nuclei. Discriminant analysis selected seven karyometric features that produced a statistically highly significant separation of adenoma nuclei from control nuclei. A similar analysis selected six features that produced a statistically highly significant discrimination of normal-appearing nuclei from control nuclei. The validity of these markers for distinguishing control nuclei from adenoma nuclei and normal-appearing nuclei adjacent to adenomas was demonstrated by analysis in further training and test sets. These findings parallel those previously demonstrated for invasive and microinvasive follicular carcinomas of the thyroid. PMID- 2206192 TI - Tissue architectural features for the grading of prostatic carcinoma. AB - In research for the development of a computer-aided workstation for the objective grading of prostatic carcinoma, tissue architectural (histometric) features were analyzed in ten cases each of well-differentiated, moderately differentiated and poorly differentiated carcinoma (as subjectively graded by the consensus of a panel of experts). Sections were cut at 4 microns, stained by the Feulgen reaction and digitized by two different video-based photometric systems. Some images were interactively segmented, considering the histometric clues to be studied; others were automatically segmented by an expert system-guided technique. The latter procedure produced good results, with over 90% of the nuclei judged to be correctly segmented in 64% of the fields studied and over 80% in another 24% of the fields. While the number of nuclei per field provided some separation of well-differentiated from other lesions, the number of nuclei per gland distinguished between well-differentiated and moderately differentiated lesions. Simplicial decomposition of the images also provided a measure of the degree of differentiation, as did the "texture" of the nuclear placement, based on two run-length statistics. Combination of the run-length features distinguished the three categories of lesions with statistical significance. The results of this study provided insights into the problems (such as the effect of field boundaries) faced in the design of an computer-aided grading system. They also showed the value of expert system-guided scene segmentation and of such histometric features as the field cellularity and the number of nuclei per gland for the discrimination between lesions of different grades of differentiation. PMID- 2206193 TI - Method for the quantitative evaluation of the distribution pattern of nuclei in normal and malignant endometrial epithelia. AB - A quantitative method of evaluating the pattern of distribution of nuclei within a cell cluster was developed and applied to endometrial cytology. The distribution pattern (DP) is mathematically expressed using a "DP index," which can be determined as a product of the square root of the nuclear density, square root of n0, and the mean distance between the two nearest nuclei, r. The DP index has a limited range of decreasing values from 1.074 to 0.5 to 0, indicative of regular, random and aggregated patterns of nuclear distribution, respectively. The estimated DP index was 0.831 +/- 0.031 (mean +/- standard deviation) in the clusters of normal endometrial epithelial cells from 16 nonneoplastic cases, but 0.638 +/- 0.041 in malignant epithelia from 19 cases of well-differentiated adenocarcinoma. The index of normal epithelia was close to 0.877 of the regular hexagonal distribution pattern. Contrary to this, the DP index was significantly smaller in well-differentiated adenocarcinoma (P less than .001), approaching 0.5, the theoretical value of a random distribution pattern. These findings suggest that quantitative analysis of the distribution pattern of nuclei can be a useful aid in the cytodiagnosis of endometrial lesions. PMID- 2206195 TI - Flow cytometric DNA ploidy analysis of soft tissue sarcomas. A comparative study of preoperative fine needle aspirates and postoperative fresh tissues and archival material. AB - Flow cytometric (FCM) DNA ploidy measurements on frozen fresh samples of soft tissue sarcomas were compared with the corresponding analyses on preoperative fine needle aspirates and postoperative formalin-fixed archival tissues from the same tumors. A concordance in ploidy status (diploid versus non-diploid) was obtained for 63% of the fresh tissue-fine needle aspiration (FNA) sample comparisons and for 85% of the fresh tissue-archival material comparisons. The majority of discordances in the fresh tissue-FNA sample comparisons could be explained by FNA sampling errors. In the remaining discordant cases (3 of 27 FNA sample comparisons and 6 of 40 archival material comparisons), sampling errors could not explain the differences in ploidy status. The discordant cases were evenly distributed among the different sampling methods. Method reproducibility was not responsible for the differences in ploidy determinations; tumor heterogeneity may be an explanation for the discrepancies. This study showed that archival soft tissue sarcoma samples are as well suited for DNA ploidy analysis as are fresh frozen tissues. PMID- 2206194 TI - Nucleolar topography of nuclei in histologic sections. Application of a nonparametric approach to the study of breast cancer and non-Hodgkin's lymphoma. AB - The position of the nucleolus within a near-convex nuclear profile was defined, without taking stereology into account, in terms of two distances, P and G, where P = pi p2/SN, G = pi 2/SN, p and g being, respectively, the smallest and greatest distances between the center of the nucleolus (considered as a disk) and the superficial nuclear membrane, and SN being the surface area of the nucleus. Nuclear elongation (ND) was defined by the ratio ND = SN/A, where A is the area of the largest inscribed disk. The nucleolus-nucleus ratio RS = Sn/SN (i.e., the surface of the nucleolus over that of the nucleus) describes the size of the nucleolus. A four-class classification of nucleolar topography was then developed from the model of an ellipsoid nuclear profile (1 less than ND less than 2.5), for which the probability that a randomly located nucleolus (with RS less than 0.23) will be classified as central (G less than 2.5 and 0.40 less than or equal to P less than 1) is less than 0.14, as paracentral (G less than 2.5 and 0.23 less than or equal to P less than 0.40) is less than 0.13, as "transversely eccentric" (G less than 2.5 and P less than 0.23) is less than 0.10 and as "longitudinally eccentric" (G greater than or equal to 2.5) is greater than 0.66. This theoretical distribution into four classes was compared to that of nuclear profiles in four cases of breast cancer and in typical cases of immunoblastic, centroblastic and Burkitt's non-Hodgkin's lymphomas. The findings illustrate the ability of this nonparametric method to indicate characteristic nucleolar locations in relation to the number of nucleoli, their size and their nuclear profile elongation. PMID- 2206196 TI - Performance of a TV image analysis system as a microdensitometer. AB - The performance of a TV image analysis system combined with an automated microscope (the Leitz TAS plus) as a microdensitometer and morphometric device was investigated. There was a strict linear correlation (r greater than .99) between the physically defined optical transmission values and the resulting electronic signals from the plumbicon TV camera for the whole area displayed on the monitor. The shading of the optoelectronic system had a coefficient of variation (CV) of 1.42% for measurements in the center of the displayed area, but a CV of 3.55% for measurements over the whole monitor area. Densitometric measurements remained stable 15 minutes after putting the microscope lamp into operation (T less than 0.075%, remeasuring every two minutes). The geometric distortion, measured as different ferret diameters of ideally round latex particles, ranged from +/- 0.5% to +/- 1.0% deviation over the entire displayed area. These results indicate that densitometric and morphometric measurements with this equipment are sufficiently precise and reproducible when performed in the center of the area displayed on the monitor. PMID- 2206197 TI - Megakaryocyte precursors (promegakaryoblasts and megakaryoblasts) in the normal human bone marrow. An immunohistochemical and morphometric study on routinely processed trephine biopsies. AB - On routinely processed trephine biopsies of the normal human bone marrow derived from 15 patients, immunostaining with a monoclonal antibody against platelet glycoprotein IIIa (Y2/51) and morphometric measurements were performed for the determination of megakaryocyte precursor cells. Based on cell sizes and on comparison with (1) specimens stained by the periodic acid-Schiff reaction and (2) smears, the smallest elements clearly identifiable as belonging to the megakaryocyte series were classified as promegakaryoblasts. Promegakaryoblasts had a frequency of 1.7/sq mm and 140/cu mm of bone marrow and constituted about 8% of the total positively stained megakaryocytic elements; they were characterized by a size of 41.5 sq microns, a diameter of 7.7 microns, a high nuclear-cytoplasmic ratio (0.32) and a nearly circular outline of their nuclear and cellular perimeters. PMID- 2206199 TI - Isolations of protein A and protein G from the bacterial surface. AB - Ten tested cultures each of Staphylococcus aureus (S. aureus) and of Streptococcus belonging to serological group G bound human IgG to a high extent. Protein A could be solubilized from strain Cowan I of S. aureus by lysozyme, mutanolysine, hydroxylammoniumchloride, hot acid extraction or lysostaphin and subsequently purified by affinity chromatography on human IgG-sepharose. The purified protein A preparation had molecular weights between 29,000 and 63,000 D and inhibited binding of 125I-labeled human IgG to S. aureus Cowan I. Protein G could be solubilized from strain 26540 of the G-streptococci with lysozyme or hot acid extraction and purified by affinity chromatography on human IgG-sepharose. The purified protein G revealed a molecular weight of 67,000 D and inhibited binding of human IgG to the G-streptococci. PMID- 2206198 TI - Cell surface proteins from Shigella dysenteriae type 1. AB - A simple extraction procedure was used for preparing cell surface proteins (CSPs) from Shigella dysenteriae type 1. The preparations obtained using either buffer or water extractions were free from lipopolysaccharide (LPS), as well as cytoplasmic and periplasmic proteins. By SDS-PAGE, about 25 polypeptides were detected, and Western-blot analysis recognised 15 polypeptide antigens. When analysed by crossed immunoelectrophoresis, using anti-Shigella dysenteriae type 1 rabbit sera, 18 antigenic bands were identified. Proteins obtained by this method were found to be highly immunogenic in rabbits. The cell-surface proteins were compared to outer membrane proteins (OMPs) obtained from the S. dysenteriae type 1 strain by a standard procedure involving lysozyme-EDTA extraction, sucrose density centrifugation, and detergent treatment. They were found to contain periplasmic, cytoplasmic, and lipopolysaccharide contaminants. Thus, the procedure described here offers a quick and simple alternative for obtaining relatively pure cell surface proteins from Shigella dysenteriae type 1. This method will be useful when immunogenically active proteins free from other cellular components are required for studies. PMID- 2206200 TI - Determination of plasmid-associated hydrophobicity of Yersinia enterocolitica by the salting-out test. AB - The hydrophobicity of the cell surface of Yersinia enterocolitica was investigated by the salting-out test. It was shown that plasmid-containing strains grown at 37 degrees C aggregated at a final concentration of (NH4)2SO4 of between 0.3 to 0.5 M. In contrast, the plasmid-free derivatives did not show aggregation even at a concentration of 2.0 M(NH4)2SO4. Therefore, the salting-out test can be utilized as a simple and reliable method for distinguishing plasmid containing, virulent strains of Yersinia enterocolitica from their plasmid-free derivatives. This was also confirmed by the use of 30 clinical isolates of virulent Y. enterocolitica. PMID- 2206201 TI - International collaborative evaluation of the ATB 32 staph gallery for identification of the Staphylococcus species. AB - This international collaborative study evaluates a new system (ATB 32 Staph) for the identification of staphylococci taking into account the new novobiocin sensitive and -resistant species reported. This study involved eight laboratories and 792 strains were tested. The reproducibility obtained for the cumulative results of the inter- and intra-laboratory tests was more than 90%. For 713 strains relevant of a species 95.5% were correctly identified by the system. Eight strains (1.2%) were misidentified and 24 strains (3.3%) were not identified. For 79 strains initially considered as not-classified, 62% were identified at the species level by the new system. The newer ATB 32 Staph gallery is a performant and useful method for routine identification of the currently described staphylococci species from clinical and animal origin. PMID- 2206202 TI - Temperature as an environmental factor influencing the pathogenicity of Aeromonas hydrophila. AB - Contamination of wounds by surface water and the aspiration of such water following an accident can lead to severe septic infection by A. hydrophila. As such water is often found at low temperatures, the question should be asked whether this particular water environment influences the pathogenicity of this organism. Some experiments have been undertaken to assess if the pathogenicity of A. hydrophila is affected by temperature. The pathogenicity of A. hydrophila adapted to the low temperature of ground and surface waters (10 degrees C) was tested in a mouse-model. The conclusions drawn from the experimental data indicate that the 50 per cent lethal dose of A. hydrophila suspensions are lower for those grown at low temperatures (10 degrees C) when compared to those grown at higher temperatures (30 degrees C). The generation and log phase periods support the above conclusion, in so far that low-temperature-adapted organisms, when exposed to high temperatures, grow faster than those organisms already adapted to higher temperatures. PMID- 2206203 TI - Comparative pathogenicity of a wild-type strain and respiratory mutants of Candida albicans in mice. AB - The pathogenicity of a parent wild-type strain and three respiratory mutants of Candida albicans was examined in intravenously infected mice. The wild-type strain K grew well in the kidney and caused severe candidosis, and the 21-day LD50 value was 7.2 x 10(6) cells/mouse. A mutant with a low rate of respiration (KRD-8) whose growth rate in vitro was somewhat lower than that of the wild type, produced germ tubes in vitro to the same extent as the wild-type strain and was associated with mortality rates similar to those of the wild-type strain. Two respiration-deficient (petite) mutants (KRD-19 and KRD-51), whose growth rates in vitro were far lower than that of the wild-type strain, could neither colonize the kidney nor cause fatal infection, even at a dose of 10(8) cells/mouse. Formation of germ tubes and hyphal growth in vitro of the petite mutants were less extensive than those of the wild-type strain or KRD-8. Extracellular proteinase was produced at pH 3.5 by the wild-type strain and by KRD-8 but not by the petite mutants. From these results, it is most likely that the nonlethality of infection by the petite mutants in mice results primarily from the low capacity of growth of these mutants, even though the inability of the petite mutants to produce extracellular proteinase may be also related to some extent to their avirulence. PMID- 2206204 TI - Common antibiotic resistance plasmids in Staphylococcus aureus and Staphylococcus epidermidis from human and canine infections. AB - The plasmids of a multiresistant "canine" Staphylococcus epidermidis-culture were investigated. Two small plasmids, the 4.55 kB chloramphenicol resistance (CmR-) plasmid pSC4 and the 4.45 kB tetracycline resistance (TetR-) plasmid pST 3 could be isolated. Detailed restriction maps of pSC 4 and pST 3 were constructed by double restriction endonuclease digests. The restriction maps revealed extensive structural homologies between pSC 4 from "canine" S. epidermidis and the CmR plasmid pC 221 from "human" S. aureus as well as between pST 3 from "canine" S. epidermidis and the TetR-plasmid pT 181 from "human" S. aureus. These data suggested that an exchange of small plasmids between S. epidermidis and S. aureus might be possible. PMID- 2206205 TI - Behaviour of lymphocyte subsets in response to immunotherapy with Propionibacterium avidum KP-40 in cancer patients. AB - In 15 patients the influence of unspecific immunostimulation/immunomodulation was studied. Patients constituting the therapeutical group suffered from colorectal- and gastric carcinoma, respectively, and were preoperatively treated with 10 mg whole cell preparation of immunomodulating Propionibacterium avidum KP-40. This adjuvant immunotherapy resulted in a significant increase (p less than 0.01) of the natural killer (NK)-cell population, however, total leukocyte and lymphocyte count as well as helper- and suppressor T-lymphocyte subsets did not significantly differ form control values. PMID- 2206207 TI - Caries diagnosis within restored teeth. AB - Secondary caries is the most common reason given by dentists for the replacement of restorations, and yet this is a diagnosis that is difficult to make with confidence. This paper attempts to define some of the problems in the diagnosis of caries in restored teeth. The histology of the secondary carious lesion shows that it may be considered in two parts: an outer lesion adjacent to the filling, and a wall lesion which will occur only if there is leakage between the filling and the tooth. The specific diagnostic difficulties addressed are the difficulty of seeing this wall lesion, whether a defective margin indicates secondary caries, and the difficulties of differentiating secondary from residual caries and active from arrested disease. Since further research is needed to solve many of these problems, the paper ends by discussing the consequences of these difficulties for clinicians, epidemiologists, teachers, and research workers. PMID- 2206206 TI - Modulation of experimental systemic murine candidosis by intravenous pepstatin. AB - The effect of intravenous pepstatin-A on systemic candidosis in NWNI mice was investigated. True solutions of the inhibitor proved ineffective due to a very fast clearance. Pepstatin was effective as a crystal suspension (0.69 mg in 0.1 ml saline) which produced serum inhibitory activity for greater than 29 h. From the intravenously applied suspension, pepstatin was taken up predominantly into the liver, no inhibitor being taken up by the kidneys. The suspension was protective if it was injected once before the mice were infected and repeatedly following infection. It was also effective if it was administered concomitantly with the infecting agent and thereafter. The suspension was ineffective if it was only given once before infection, and it proved to be detrimental if it was given only after infection. The results support previous findings (2), suggesting a role of fungal proteinase early in the adherence of Candida to host epithelia. Our results also suggest an inhibition of lysosomal cathepsin-D in vivo by pepstatin, which prohibits a parenteral therapeutic use of nonmodified pepstatin A. PMID- 2206208 TI - Deterioration of restorative materials and the risk for secondary caries. AB - This article reviews the literature related to marginal deterioration of amalgam restorations and the risk for secondary caries. Background information on this characteristic material failure is provided, including how it is measured clinically, its rate of progress with time, and the responsible microstructural mechanisms. The association between degree of marginal fracture and recurrent or secondary caries is reviewed in clinical and in vitro studies. Earlier clinical investigations and a more recent laboratory study demonstrated a strong correlation between gap size and recurrent caries for a caries-active environment, supporting replacement of defective restorations for preventive reasons. However, more recent clinical data show the complex and equivocal nature of this association. Poor specificity and validity for detection of recurrent caries with an explorer and mirror further complicate interpretation of some trials and decision-making in clinical practice. Improved methods of diagnosing recurrent caries and further studies of the factors influencing its initiation and progression are needed. PMID- 2206209 TI - Practice variation: learned and socio-economic factors. AB - Much variation exists in the practice of dentistry with regard to diagnosis of caries and recommendations for treatment. This is a particular problem with respect to the replacement of restorations, with responsible factors related to both the patient and the dentist. The aim of this paper is to look at factors, exclusive of clinical data, that may explain why there is so much variation in the practice of dentistry, and specifically pertaining to replacement of restorations. Due to the paucity of studies related specifically to dentists, findings from physician studies will be presented. No studies are available that compare variation in medical and dental practices, but since both professions deal with the provision of health care and function in similar circumstances, comparisons are arguably generalizable between the two groups. Development of clinical judgment will be explored based on dental training experiences, and two explanatory models of practice pattern variation will be discussed--the dentist as a self-fulfilling practitioner and the dentist as the patient's agent. Along with these models, the matter of uncertainty in clinical practice and the development of routines will also be discussed in light of explaining variations. PMID- 2206210 TI - The role of extracellular matrix in the morphogenesis and differentiation of salivary glands. AB - The processes of morphogenesis and cytodifferentiation are partially linked, independently regulated processes. The full expression of both processes is modulated or controlled, at least in part, by components of the extracellular matrix. This paper reviews the body of work that demonstrates a role for epithelial-mesenchymal interactions and various extracellular matrix molecules in the induction, control, and maintenance of salivary gland morphogenesis and cytodifferentiation. In addition, new, preliminary information which further elucidates the role of laminin and type IV collagen in the processes of morphogenesis and cytodifferentiation is presented. With regard to the role of extracellular matrix molecules in the regulation of salivary gland morphogenesis and cytodifferentiation, it appears that types I, III, and IV collagen, laminin, and chondroitin sulfate proteoglycan play roles in the control of glandular morphogenesis. With the exception of type IV collagen, these molecules do not appear to be involved in the regulation of cytodifferentiation of salivary gland secretory cells. On the other hand, of the extracellular matrix molecules tested so far, only type IV collagen appears to play a role in the regulation of salivary gland secretory cell differentiation. PMID- 2206211 TI - Three-dimensional localization of DNA synthesis in secretory elements of adult female mouse submandibular gland. AB - A system based in part on three-dimensional structural relationships is described for precisely characterizing the location of cells within secretory complexes of the adult female mouse submandibular gland. The pattern of DNA synthesis during a 90-minute pulse with 3H-thymidine was characterized based upon the above system. Seventy-eight percent of all radiolabeled nuclei were found in the intercalated duct system. One-half of these were in second-order intercalated ducts. DNA synthesis was also observed in acinar cells, granular intercalated duct cells, striated granular duct cells, and granular duct cells. Some secretory complexes contained multiple radiolabeled nuclei, with some of these nuclei in a side-by side configuration. Approximately one-half of all secretory complexes contained radiolabeled nuclei. A second survey of the frequency of complexes containing radiolabeled nuclei was conducted following four pulses at eight-hour intervals over a 26-hour period. Only about 30% of all complexes contained radiolabeled nuclei. This reduction in the frequency of radiolabeled nuclei when compared with the single pulse suggests the possibility of individual variation. However, a more prolonged period of daily injections for nine days with 3H-thymidine resulted in all but one of the secretory complexes containing radiolabeled nuclei. This latter observation suggests that cell addition in adult submandibular glands is widespread. PMID- 2206212 TI - Clinical studies concerning re-restoration of teeth. AB - Re-restoring teeth is an important component of operative dentistry, and the perceived presence of secondary caries is a major reason for undertaking it. In the absence of a diagnosis of secondary caries, a morphological discrepancy at the margin of a restoration commonly provides the necessary justification for replacement. However, several studies have demonstrated enormous variation among dentists, both in their diagnosis of secondary caries and in the clinical decisions they make regarding whether or not to restore or re-restore. Many of these decisions must have been wrong. Decisions to re-restore teeth have been shown to be particularly idiosyncratic, and some patients apparently become involved in a repeat restoration cycle whereby the more restorations they have, the more re-restorations they receive. The desire by some dentists to replace large numbers of restorations, for reasons other than the presence of disease, shows a fallibility of operative treatment. At the same time it suggests that these dentists have considerable faith in this aspect of dental care. There would appear to be a prima facie case for investigating more deeply the factors involved in the clinical assessment of restorations. It should then be possible to improve the standard of diagnosis and treatment decision-making, especially with respect to the need to re-restore teeth. PMID- 2206213 TI - The role of myc oncogenes in cell growth and differentiation. AB - The myc oncoproteins are expressed in a wide range of normal adult and embryonic tissues. They are also found to be over-expressed in a variety of tumor types. All myc proteins are short-lived nuclear phosphoproteins thought to act as regulatory components of cell proliferation. The rapid induction of c-myc mRNA and protein following the addition of growth factors to quiescent cells, together with the short half-life of these molecules, suggests that they are sensitive and continuous indicators of external stimuli, consistent with a role in signal transduction. Furthermore, in untransformed cells, c-myc protein expression is tightly regulated, at least in part, by a mechanism of autoregulation. Deregulated expression of myc genes is a frequent observation in tumors and may lead to a cell becoming independent of one or more growth factors, with the concomitant potential for uncontrolled proliferation. Although the precise functions of the myc proteins are unknown, they all bear the hallmarks of multimeric DNA-binding proteins probably involved in the regulation of expression of specific genes. PMID- 2206214 TI - Anesthesia for liver transplantation in patients with arterial hypoxemia. AB - Arterial oxygenation during anesthesia and time of postoperative mechanical ventilation were investigated in 17 patients with chronic liver disease who underwent liver transplantation. Six patients had arterial hypoxemia (PaO2 64 +/- 3 mm Hg) and the other 11 patients had normal PaO2 (105 +/- 5 mm Hg) before transplantation. None of the patients were smokers and all had normal preoperative pulmonary X-ray and spirometry. During transplantation, PaO2 increased in both groups, but PaO2 was still approximately 20% lower and PA-aO2 was 40%-60% higher in the hypoxemic group than in the normoxemic patients (P less than 0.05). The median postoperative time on mechanical ventilation was three times longer in the hypoxemic group (56 h) than in the normoxemic patients (18 h; P = NS). Number or severity of postoperative complications and outcome did not differ between the two groups. It is therefore suggested that patients with arterial hypoxemia without overt lung disease should also be accepted for liver transplantation. PMID- 2206215 TI - Validation of impedance cardiography measurements of cardiac output during limited exercise in heart transplant recipients. AB - Twenty-one patients were studied at rest and during exercise after heart transplantation to compare cardiac output measured by thermodilution and impedance cardiography. Exercise was performed on a bicycle ergometer over a limited range of work load (25 and 50 watt) whilst metabolic gas exchange was recorded. One patient was studied at rest whilst his circulation was maintained by a Jarvik-7 artificial heart. The values of cardiac output measured by impedance cardiography corresponded closely with the flow rate from the artificial heart. There was also close agreement between the impedance and thermodilution measurements of cardiac output at rest and during exercise. Both measurements followed the changes in heart rate and oxygen consumption. Both thermodilution and impedance cardiography methods elicited good reproducibility of cardiac output measurements at rest and during exercise. These observations suggest that the noninvasive and continuous record of cardiac output obtained by impedance cardiography can be used for the postoperative monitoring of heart transplant recipients. PMID- 2206216 TI - Disseminated tuberculosis after renal transplantation. A report of two cases. AB - Disseminated mycobacterial infections occurred in two female renal graft recipients late after transplantation. In the first patient, initially presenting with fever, diagnosis was made at autopsy. Temporary defervescence following antibiotic therapy with ofloxacin possibly contributed to the fatal diagnostic delay. In the second case, body temperature was normal throughout the protracted course of the patient's illness. Her presenting symptom was rapidly increasing ascites, attributed initially to chronic liver disease. These cases demonstrate that tuberculosis remains a serious complication after renal transplantation, in particular due to its sometimes atypical clinical manifestations. Response to antibacterial therapy has to be critically evaluated in order to avoid fatal diagnostic delay. PMID- 2206217 TI - The use of the hypogastric artery in the anastomosis of multiple renal arteries in the transplant patient. AB - Alternative techniques for handling multiple renal vessels in living related kidney transplants by use of the hypogastric artery are presented. This vessel can be used either as a tubular vascular graft or as a Carrel patch graft. Details of these techniques are discussed. PMID- 2206218 TI - Blood lymphocyte subsets in ATG-treated and allografted rats. AB - A single dose of rabbit antithymocyte globulin (ATG) was given as the sole immunosuppressive therapy in a model of strong MHC barrier rat heart allotransplantation. PVG/c hearts transplanted to Wistar/Kyoto (WKy) rats resulted in long-term surviving (LTS) grafts and cell-mediated lympholysis (CML) unresponsiveness in 50% of the animals. The effects of ATG treatment on the peripheral blood lymphocyte subsets were studied by flow cytometry. The absolute T-lymphocyte levels decreased to less than 5% and were normalized after 2 weeks. CD8-positive cells were normalized within 1 week, whereas CD4- and CD5-positive cells remained low. Rats with LTS grafts had low levels of all T-lymphocyte markers, especially the CD4- and CD5-positive cells. Rats rejecting their grafts showed an eightfold increase in levels of CD8- and CD5-positive lymphocytes and a twofold increase in levels of CD4-expressing lymphocytes. It is concluded that ATG treatment causes the immediate elimination of large lymphoid populations as well as long-lasting immunomodulation detectable in peripheral blood. PMID- 2206219 TI - Cardiac transplantation beyond 55 years of age. AB - Between January 1985 and December 1988, 20 patients over the age of 55 years (extremes 56-63 years; 15 men and 5 women) underwent cardiac transplantation. The cause of cardiopathy was ischemic in 70% of the cases. The immunosuppressive regimen consisted of cyclosporin A, corticoids, and azathioprine. Rejection episodes were monitored by endomyocardial biopsies and treated by pulses of corticoids or monoclonal antibodies (OKT3). The operative mortality was 10% (n = 2). The 1-year survival rate was 70%. The 1-year incidence of infection and/or rejection episodes was 1 and 1.53 episodes/patient, respectively. One patient was successfully retransplanted after 9 months because of intractable rejection. Age beyond 55 years is no longer a contraindication to cardiac transplantation. This change in recipient selection policy should lead to parallel changes in donor selection criteria. PMID- 2206220 TI - Short-term high-dose corticosteroids and gastroduodenal mucosa. A prospective clinical study on renal transplant recipients. AB - In order to evaluate the effect of a short-term high-dose corticosteroid therapy on the gastric and duodenal mucosa, 30 consecutive renal transplant recipients (mean age 39.1 years, 10 women and 20 men) underwent an endoscopic examination of gastroduodenal mucosa 12 and 30 days after renal transplantation. In addition to the postoperative immunosuppressive medication (methylprednisolone and azathioprine), antacids and H2-receptor antagonists were given. Seventeen patients showed no signs of acute rejection, whereas 11 patients experienced one episode and 2 patients two episodes of rejection during endoscopic follow-up. Each rejection episode was treated with a high-dose regimen of methylprednisolone. The two groups of patients studied, i.e., those who did and those who did not experience rejection, were matched for age, sex, period of preoperative dialysis treatment, period of postoperative time elapsed from transplantation, serum creatinine level, and dose of methylprednisolone or azathioprine at the beginning of the endoscopic follow-up, as well as for ulcer prophylactic medication during follow-up. The gastroduodenal mucosa was similar in the two patient groups, both endoscopically and histologically, at the start of the study. During the observation period of 2 weeks, erosive antral gastritis increased significantly in patients who did not experience rejection, whereas in patients with acute rejection and concomitant high-dose corticosteroid therapy, the antral mucosa remained nearly unchanged. Also, the gastric corpus and the duodenum remained unaltered in both groups during follow-up. No ulcer complications occurred in the series.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206221 TI - Novel antibodies associated with unexplained loss of renal allografts. AB - Using an endothelial/epithelial hybrid cell line, three different non-HLA antibody types have been identified by flow cytometry in patients who have rapidly rejected multiple renal allografts. These antibodies may be classified as anti-endothelial-monocyte, anti-activated endothelial cell, or anti-epithelial cell. PMID- 2206222 TI - Cyclosporin A-induced tolerance is not amplified by the addition of a steroid therapy. AB - The effect of adding steroids to a cyclosporin A (CyA) schedule designed to induce tolerance to heart allografts in rats was investigated. CyA treatment alone, at a dose of 15 mg/kg per day for 2 weeks, resulted in the successful induction of tolerance (graft survival greater than 100 days) in 70% of the rats. The inclusion of 5 mg/kg of steroids (Solumedrone), administered IM for 40 or 60 days, not only failed to improve this long-term survival (LTS) rate achieved with CyA alone but reduced it from 70% to 50% after 40 days of steroid treatment and to 30% after 60 days of steroid treatment. The administration of 5 mg/kg and 40 mg/kg of steroids during the "high-risk" period for graft rejection (days 30-50 or 40-60) was shown to delay but not prevent subsequent rejections from occurring. Steroid treatment alone (5 mg/kg per day) was found to be ony weakly immunosuppressive. Thus, we have demonstrated that the addition of steroids to a CyA tolerizing schedule was detrimental to the induction of tolerance. PMID- 2206223 TI - Altered distribution of MHC class II antigens on enterocytes during acute small bowel allograft rejection in rats. AB - Class II major histocompatibility complex (MHC) antigen induction was investigated on enterocytes of heterotopic rat small bowel allografts in the Lewis-Brown Norway strain combination and on isografts in the Lewis-Lewis strain combination. Ia antigens were detected with monoclonal antibodies using an immunoperoxidase technique. Generally, MHC class II antigens were not exhibited in the isografted group, with the exception of two long-term isografts that presented the same pattern as normal small bowel. In these cases, Ia was expressed in a patchy distribution predominantly in the villi, and only very few enterocytes stained positive in Lieberkuhn's crypts. Allografted rats showed a typical pattern of Ia expression on the enterocytes during the rejection course. The initial expression was confined to the crypts, indicating a very early stage of rejection when compared to histological findings. More advanced stages of rejection were accompanied by increasing Ia biosynthesis in the crypts and Ia expression by the epithelium lining the villi. Cyclosporin (CyA) was not able to fully inhibit MHC class II antigen expression; however, the appearance of Ia was delayed. PMID- 2206224 TI - Evaluation of the liver graft before procurement. Significance of arterial ketone body ratio in brain-dead patients. AB - Hepatic energy metabolism was assessed by measuring the blood ketone body ratio (KBR), that is, the ratio of acetoacetate to beta-hydroxybutyrate in the arterial blood, in 31 brain-dead patients in an intensive care unit (ICU) in Japan and in 25 donors just before procurement of the liver for transplantation in Germany. In the study in Japan, 7 of the 12 brain-dead patients treated with high-dose catecholamine showed significantly decreased KBRs, revealing the detrimental effect of catecholamine on liver metabolism. In contrast, 8 of the 9 untreated patients with blood pressure below 80 mm Hg showed almost normal KBRs. In the 25 donors in Germany, KBR was maintained within the normal range. Based upon conventional criteria, 21 livers were selected for use and the other 4 were discarded. Nineteen of the grafts were able to normalize KBR within 24 h after reperfusion, while 2 failed to function and required a second transplantation. It was suggested that a KBR in the normal range in donors is a prerequisite to immediate recovery of metabolic function of the liver graft after transplantation, and that hypotensive donors as a potential source of liver grafts may warrant further study. PMID- 2206225 TI - Failure of two subsequent renal grafts by anti-GBM glomerulonephritis in Alport's syndrome: case report and review of the literature. AB - We describe a patient with Alport's syndrome who developed severe crescentic glomerulonephritis after each of two successive transplantations, leading to accelerated graft failure on both occasions. This complication occurred in the 7th postoperative month for the first transplant and in the immediate postoperative period for the second. Immunopathological studies of the second transplant demonstrated that the glomerular lesions were mediated by antiglomerular basement membrane (GBM) antibodies displaying the same pattern of reactivity as the MCA-Pl monoclonal antibody directed against the Good-pasture antigen. This observation indicates that the anti-GBM immunization induced by renal transplantation in some patients with Alport's syndrome may be responsible for recurrent graft failure. PMID- 2206226 TI - The frequency of B cells secreting antibodies against donor MHC antigens in rats rejecting renal allografts. AB - We have estimated the frequency of B cells secreting antibodies against donor MHC antigens in rats rejecting histoincompatible renal allografts. In a major plus minor antigen-incompatible DA-to-WF combination on day 4 post-transplantation, reverse protein A plaque assay demonstrated that in the graft the frequency of lymphoid cells secreting Ig was 1:850. A major locus-incompatible and minor locus compatible, congeneic LBN-to-Lewis strain combination was then applied to estimate the specificity of the secreted antibody. The lymphoid inflammatory cells were fused with mouse myeloma cells, cultured under limiting dilution conditions, and assayed by ELISA to donor and irrelevant strain spleen cells. Among cells infiltrating the graft, the fusion frequency was 1:172 x 10(3) and the frequency of Ig-producing hybrids 1:400 x 10(3) (i.e., this assay was approximately three log orders less sensitive than the reverse pA assay). The frequency of hybridomas secreting specifics antibodies against donor MHC antigens was 1:720 x 10(3) (i.e., every second hybridoma deriving from inflammatory population produced specific Ig). In addition, there was at least one obviously polyspecific population of hybridomas, detectable only in the spleen and reactive with all rat strains tested with a frequency of 1:700 x 10(3). The inflammatory cells were also cultured directly under limiting dilution conditions, and the frequency of Ig-secreting cells was determined by ELISA. The frequency of inflammatory lymphocytes secreting detectable amounts of immunoglobulin in the supernatant was 1:14 x 10(3) in the graft (i.e., this assay was approximately one log order less sensitive than the reverse protein A plaque assay).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206227 TI - Renal allograft immunosuppression. I. Early inflammatory and rejection episodes in triple drug treatment compared to double drug combinations or cyclosporin monotherapy. AB - We have investigated the impact of triple drug immunosuppression on the occurrence of early inflammatory episodes, as detected by fine needle aspiration biopsy, and of episodes of clinical rejection during the immediate postoperative period. The prospective component of this study includes 128 consecutive first cadaveric renal transplant recipients receiving triple drug treatment consisting of azathioprine (Aza), cyclosporin (CyA) and methylprednisolone (MP). For controls we have used three historical groups: one immunosuppressed with Aza and MP (group A), another with CyA monotherapy (group B), and the third with CyA together with MP (group C) in equivalent drug dosages. On the average, 0.8 episodes of inflammation per patient were recorded during the immediate postoperative period of 30 days with triple drug treatment. This was significantly less than the 1.3 episodes in patients receiving Aza and MP (P less than 0.01), the 1.7 episodes in patients on CyA monotherapy (P less than 0.001), or the 1.6 episodes in patients receiving CyA together with MP (P less than 0.001). Although the first episode of inflammation commenced concurrently in each group and the peak intensity of inflammation was the same, the mean duration of inflammation was significantly shorter--2.7 days--under triple drug treatment than the 7.8-11.7 days for controls (P less than 0.001). The frequency of rejection episodes under triple treatment was also significantly lower--0.2 per patient--than the 0.8 per patient in controls (P less than 0.001). The first rejection episode occurred later in the triple drug treatment group--on the average, on day 15.2--than in the historical controls (on days 7.7 11.7).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206228 TI - Prognostic risk factors for graft failure following pancreas transplantation: results of multivariate analysis of data from the International Pancreas Transplant Registry. AB - A multivariate analysis of prognostic factors for graft failure was performed on patients in the International Pancreas Transplant Registry. The analysis was restricted to the period January 1978 to June 1987 and included 764 patients. All patients had at least 1 year of follow-up. The following variables were studied: transplant year, continent (N. America, Europe, others), type of donor (cadaver, living related mismatched, living related HLA-identical), donor mismatch at the HLA A, B loci, donor mismatch at the DR loci, preservation time, kidney association (pancreas transplant alone, simultaneous pancreas and kidney transplant, pancreas after kidney transplant), whole versus segmental pancreatic transplant, graft duct management technique (polymer injection, enteric drainage, stomach drainage, bladder drainage), and immunosuppression. By stepwise, logistic regression analysis, we found that the following factors were predictive for 1 year graft function: donor mismatch at the DR loci (P = 0.0003), kidney association (P less than 0.0001), type of donor (P = 0.04), and immunosuppression (P = 0.0002). For donor mismatch at the DR loci, we found an odds ratio for success of 2.2 for 0 versus 2 mismatches. The odds for success were 2.9 for simultaneous pancreas and kidney transplant versus pancreas transplant alone. The best results--79% 1-year graft survival--were obtained for the combination of 0 mismatches at the DR loci, pancreas after kidney transplant, living related HLA identical donor, and the immunosuppressive regimen consisting of cyclosporin, azathioprine, and prednisone. Patients receiving a pancreas transplant alone with 0 mismatches at the DR loci, living related HLA-identical donor, and triple immunosuppressive regimen had a predicted 1-year graft survival of 71%. PMID- 2206229 TI - The public health nurse--the linchpin of primary health care. AB - Finland is an example of a country in which primary health care has been put successfully into practice. This could not have been done without the help of public health nurses. At a time when socioeconomic and health status was low, a simple and effective public health nursing service was created to bring primary care to people in their homes and neighbourhoods. PMID- 2206230 TI - Nurses bring primary health care to industrial workers. AB - Progress in bringing health care to the workplace lags considerably behind progress in bringing health care to where people live. Experience in Botswana shows that the family nurse practitioner--a registered nurse midwife with one year of post-basic training--can provide useful preventive and curative services to people in their places of work. PMID- 2206231 TI - Consensus statement from the consultation on HIV epidemiology and prostitution. PMID- 2206232 TI - Strengthening community-level AIDS prevention and care. PMID- 2206233 TI - AIDS in women and children. PMID- 2206234 TI - World AIDS day 1990 to focus on women. PMID- 2206235 TI - AIDS postage stamps. PMID- 2206236 TI - Health in strip cartoons. AB - Strip cartoons are among the most vivid means of communication at our disposal, and they are particularly popular with the young. Medical matters have featured in many stories, though usually in a peripheral role. Could more be done to use this powerful medium, or would deliberate exploitation destroy it? PMID- 2206237 TI - Women and tobacco. PMID- 2206238 TI - Attitudes to environment. AB - An opinion survey covering 16 countries, both developing and developed, revealed widespread concern about environmental deterioration. Many people felt that more should be done to reverse present trends, even if this meant forgoing some material gains. PMID- 2206239 TI - Home and health--on solid foundations? AB - This article is based on a WHO survey confirming that a large part of humanity lacks adequate shelter or knowledge of how to obtain the best possible health benefits from housing. The reasons for this state of affairs, and the health sector's role in overcoming it, are discussed. PMID- 2206240 TI - The future of primary health care in India. Interview by Johannes Holm. PMID- 2206241 TI - World Health Forum: what the readers think. PMID- 2206242 TI - Software for data management and analysis in epidemiology. AB - The collection of data is a lengthy and time-consuming process, but is not an end in itself. For the data to be useful, it is necessary for an appropriate analysis to be made and its results applied. This article describes a computer program for the analysis of epidemiological studies. PMID- 2206243 TI - Prospects for higher infant survival. AB - Studies on trends in infant mortality and its constituent elements of early neonatal, late neonatal and postneonatal death, in developed and developing countries, point to ways of making further progress towards the target of infant mortality rates not exceeding 50/1000 live births in all countries by the year 2000. PMID- 2206244 TI - National community health worker programmes. PMID- 2206245 TI - Supervision of village health workers. PMID- 2206246 TI - Towards better health in Nigeria. PMID- 2206247 TI - Safety of herbal medicines. PMID- 2206248 TI - Conservation of medicinal plants in the USSR. PMID- 2206249 TI - Malaria--the economic threat. PMID- 2206250 TI - Measurement of trends in health status. PMID- 2206251 TI - Vitamin D deficiency in patients with fractured neck of femur. PMID- 2206252 TI - A levy on tobacco, alcohol and petrol for health education? PMID- 2206254 TI - Personal approach vital in health education. PMID- 2206253 TI - Comprehensive data essential for research on road accidents. PMID- 2206255 TI - Radio announcements to promote the use of condoms. PMID- 2206256 TI - The uphill task of adapting medical education to community care. PMID- 2206257 TI - Nurses, midwives and health research. AB - Despite the wealth of researchable topics in maternal and child health, it is rare for studies in this field to be carried out by nurse-midwives. This article explores the historical origins of nursing, its educational characteristics and its dominance by women, identifying obstacles to independent research and pointing to ways of overcoming them. PMID- 2206258 TI - Shy-Drager syndrome presenting as a REM behavioral disorder. AB - Shy-Drager syndrome (SDS) is associated with a myriad of autonomic and neurologic impairments, including sleep disturbances. A review of the literature reveals that there are no reports of SDS presenting with an abnormality of sleep. The following case report describes a patient who was diagnosed with SDS approximately one decade after initially presenting with a progressive, polysomnographically confirmed disturbance of sleep--specifically, an REM behavioral disorder (RBD). PMID- 2206259 TI - The dental management of the depressed patient. PMID- 2206260 TI - Binswanger's disease: a complete translation. PMID- 2206261 TI - The impact of Alzheimer's disease on driving ability: a review. AB - As our elderly population continues to increase, diseases that are more prevalent with aging, such as Alzheimer's disease, are assuming ever greater relevance for society and the practicing clinician. An important practical situation faced by physicians caring for individuals with Alzheimer's disease is advising the affected individuals, their families, and often the licensing authorities about whether the patient can safely drive an automobile. Surprisingly, there is little guidance on how to arrive at a clinical impression of the fitness of an individual with Alzheimer's disease to drive. This article outlines potential inadequacies in driving skills that may occur with elderly people in general, and more specifically those with Alzheimer's disease. Studies that focused on Alzheimer's disease and driving are then reviewed. We conclude with recommendations for dealing with the problem of driving abilities in Alzheimer's disease. PMID- 2206262 TI - Diagnosis of rare dementia syndromes: an algorithmic approach. AB - The etiology of dementia can be diagnosed in most patients using a standard clinical approach consisting of physical, neurologic, and mental status examinations, and laboratory testing, lumbar puncture, and neuroimaging. In some cases, however, the clinical presentation or historical data are unusual, or the results of the workup are inconclusive or atypical. A rare cause of dementia may then be present and a complicated evaluation may be necessary to identify the specific disease process. A potentially useful approach to the diagnosis of rare dementing disorders consists of a series of diagnostic algorithms. This approach utilizes results of neuroimaging studies to guide the evaluation through additional diagnostic steps such as specific enzymatic or immunologic assays or biopsy of extraneural tissues. The disorders potentially detected by these algorithms typically have unusual clinical features such as early age of onset, abnormal neurologic signs and symptoms early in the clinical course, early personality and mood changes, extrapyramidal or cerebellar signs and symptoms, seizures, peripheral neuropathy or myopathy, and extraneural abnormalities involving the dermatologic, cardiovascular, musculoskeletal, or ocular systems. Accurate diagnosis of these rare causes of dementia is important for medical and psychiatric management, prognosis, and genetic counseling. PMID- 2206264 TI - Longitudinal cognitive decline in patients with Alzheimer's disease. AB - Progressive cognitive impairment is a defining feature of the dementia of Alzheimer's disease (AD), yet disagreement exists over which abilities decline most precipitously and which cognitive tests are more sensitive. In this study, 51 AD patients in the early to middle stages of illness and 22 age-matched normal controls were administered a battery of neuropsychological tests at 6-month intervals over a 2-year period. While the performance of the normal controls remained stable over the 2 years, the AD patients displayed progressive decline on all tests. The greatest declines occurred on tests requiring lexical/semantic processing (Boston Naming Test) and comprehension of syntactic relationships (Token Test). Performance on visuospatial tests (Wechsler Adult Intelligence Scale-Revised Block Design, Benton Visual Retention Test, Spatial Delayed Recognition Span Test) declined less rapidly. The findings support previous reports that language impairment may be central to the dementia of AD, and that confrontation naming is particularly sensitive to decline in this illness. PMID- 2206263 TI - Coping, social support, and depressive symptoms in Parkinson's disease. AB - Social support, depressive symptoms, and three methods of coping were assessed in 45 patients with Parkinson's disease (PD) and 24 comparably disabled controls. The PD subjects employed significantly fewer cognitive and behavioral coping strategies compared with the controls. Fewer depressive symptoms were related to increased cognitive coping in PD subjects. Behavioral coping strategies were associated with lesser depression among controls. Avoidance coping methods showed a marginally significant positive association with depressive symptoms in PD subjects. Social support was related to the significant coping predictors in each group, but was not related to depressive symptoms. Although correlational, these results might suggest that active (cognitive and behavioral) coping strategies are superior to avoidance strategies in attenuating the affective distress expected from chronic deteriorative illnesses. PMID- 2206265 TI - Relationship of normal serum vitamin B12 and folate levels to cognitive test performance in subtypes of geriatric major depression. AB - This retrospective study evaluated the relationships between normal serum vitamin B12 and folate levels and neuropsychologic measures in a sample of 60 geriatric inpatients with psychotic depression, nonpsychotic depression, bipolar disorder, and dementia--all consecutively referred for cognitive testing. The psychotic depression subgroup demonstrated numerous significant positive correlations between B12 and cognitive subtests not seen in other diagnostic subgroups, especially those of IQ, and verbal and visual memory. Metabolic factors including vitamin B12 may play specific roles in the cognitive dysfunctions of different geropsychiatric disorders. PMID- 2206266 TI - What's the health care workers' Bill of Rights? PMID- 2206267 TI - Astrocytes: auxiliary cells for immune responses in the central nervous system? AB - Active and replicating astrocytes are prominent in multiple sclerosis (MS) lesions and in experimental demyelinating diseases resembling MS. As evidence is amassed supporting an autoimmune etiology for MS, the possible contribution of astrocytes as auxiliary/effector cells in the generation of tissue damage and subsequent scar formation has attracted considerable attention. A recent workshop fostered interaction between neurobiologists interested in astrocytes and investigators interested in demyelinative diseases. Key issues were attempts to relate the behavior of astrocytes in demyelinative lesions to findings in model systems in vitro, to distinguish various astrocyte functions (auxiliary, effector, scar formation) and to identify the regulatory mechanisms associated with each function. PMID- 2206268 TI - Guilt by association: HLA-B27 and ankylosing spondylitis. PMID- 2206269 TI - HLA-B27 and agranulocytosis by levamisole. PMID- 2206270 TI - Central MHC genes, IgA deficiency and autoimmune disease. AB - IgA deficiency is a common immunological disorder that is sometimes associated with an immunodeficiency syndrome, allergic disease, autoimmune disease and gluten enteropathy. Many subjects with this deficiency, however, are healthy, at least for many decades. Analysis of the immunological and genetic abnormalities found in IgA deficiency and in some of the associated disorders has led to the postulate that a genetically determined defect of immunoregulation underlies all of these diseases. Here, Martyn French and Roger Dawkins propose that the products of genes located within the central region of the major histocompatibility complex (MHC) regulate B cells and/or antibody production. Particular MHC ancestral haplotypes contain specific alleles and arrangements of these genes, thereby explaining associations with either increased or decreased production of immunoglobulin isotypes by B cells. PMID- 2206271 TI - Extracellular ATP as a possible mediator of cell-mediated cytotoxicity. AB - Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells lyse target cells by a specialized mechanism that involves the release of soluble 'killer' mediators. While several possible mediators have been demonstrated, it is likely that others have yet to be identified. For more than two decades it has been known that exogenous ATP is lytic to many cell types. In this article Francesco Di Virgilio and colleagues propose that extracellular ATP may be a mediator of cytotoxic cell dependent lysis. PMID- 2206272 TI - Limiting dilution analysis of human T cells: a useful clinical tool. AB - Limiting dilution analysis (LDA) provides a practical and simple method for determining the frequency of defined clones of lymphocytes responding to a specific antigen or with a particular effector function. The importance of the technique stems from the fact that it is the only way to assess the immune response in humans, at the level of the cell, in a quantitative manner. In this article Claire Sharrock, Edward Kaminski and Stephen Man review the current status of the technique and its applications in human immunology. PMID- 2206273 TI - The history of immunology. PMID- 2206274 TI - Costimulatory function of APCs. PMID- 2206275 TI - The efficiency of antibody affinity maturation: can the rate of B-cell division be limiting? AB - It has been known for many years that the affinity of antibodies for antigen increases with time during an immune response. It is now clear that two processes play fundamental roles in this affinity 'maturation' in the mouse - V gene somatic mutation and antigen affinity-based selection. Exactly how these two processes work in concert is not fully understood. In this article Tim Manser argues that models of affinity maturation based on the assumption that somatic mutation, antigen selection and B-cell division are interdependent may not explain the high efficiency of the process, and he suggests an alternative model. PMID- 2206276 TI - The immune complex: possible ways of regulating the antibody response. AB - B cells express antigen, Fc and complement receptors on their surfaces and can thus bind all three components of an immune complex. In addition to the direct effects that they exert on cells, immune complexes may affect localization, presentation and digestion of antigen. In this article, Birgitta Heyman discusses recent developments in antibody-mediated regulation of the humoral immune response, with emphasis on in vivo systems where antigens are injected together with highly purified IgM or IgG antibodies in the absence of adjuvants. PMID- 2206277 TI - HLA and type I diabetes. PMID- 2206279 TI - The McArdle Laboratory for Cancer Research: the first fifty years. PMID- 2206280 TI - Retroviruses and cancer. PMID- 2206278 TI - Animal models for AIDS. AB - Animal models will play a central role in AIDS research in the coming years. Important models for human immunodeficiency virus (HIV)-induced disease in humans include HIV-infected great apes, simian immunodeficiency virus-infected Asian monkeys and infections of ungulates and cats with HIV-related lentiviruses. The nature of the diseases induced by these viruses are described here by Norman Letvin, emphasizing aspects with particular relevance to human HIV infections. PMID- 2206281 TI - GAP as ras effector or negative regulator? PMID- 2206282 TI - Molecular mechanisms of oxygen radical carcinogenesis and mutagenesis: the role of DNA base damage. PMID- 2206283 TI - Direct sequencing analysis of transmembrane region of human Neu gene by polymerase chain reaction. AB - The neu gene in rat neuro/glioblastoma was found to be activated by a single point mutation in the DNA sequence encoding the transmembrane region of the neu encoded p185 protein. The human homologue of the rat neu gene, termed c-erbB-2 or HER-2, can also be activated in vitro by a similar mutation in the corresponding region. Although the human neu gene was shown to be amplified/overexpressed in a large portion of human breast and ovarian cancer, no reports indicate that the human neu gene is activated by a point mutation in human tumor. To study the possible point mutation of neu gene in human tumors, we characterized the genomic structure in the transmembrane region of human neu gene, which in turn allowed us to determine DNA sequence in this region directly following DNA amplification by polymerase chain reaction. We analyzed 7 tumor cell lines (2 breast cancer, 1 neuroblastoma, 1 rhabdomyosarcoma, and 3 glioma) and 11 tumor tissue samples (8 breast and 3 ovarian cancers). No mutation was found in the transmembrane region of human neu gene. Our results suggest that unlike the rat neuro/glioblastoma, the single point mutation in the transmembrane region of the human neu gene is a rare event in human tumors. In this study, we developed a technique for direct DNA sequencing of the transmembrane region of the human neu gene. This technique makes it possible to screen a large number of tumor samples. PMID- 2206284 TI - Point mutation in codons 12 and 61 of the Ha-ras gene in rat urinary bladder carcinomas induced by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide. AB - Male F344 rats were fed N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) for up to 4 wk, then were given the basal diets (Prolab 3200 or AIN-76A) with or without 5% sodium saccharin for up to 100 wk. Eleven transitional cell carcinomas (TCCs), one undifferentiated carcinoma, and two sarcomas of the urinary bladder were examined for the expression of ras gene product, p21, by immunohistochemical staining and western blot analysis. Point mutation in codons 12 or 61 of the Ha ras genes amplified by polymerase chain reaction was examined by a slot-blot screening procedure using allele-specific oligonucleotide probes. Immunohistochemical staining showed enhanced immunoreactivity with the antibody to ras p21 in seven TCCs and one undifferentiated carcinoma. Western blot analysis showed faster migration of the p21 band in 6 of 11 TCCs. Oligonucleotide hybridization revealed the point mutation in codon 12 of Ha-ras gene (GGA----GTA in 1 TCC) and in codon 61 (CAA----CGA in 5 TCCs and CAA----CTA in 1 TCC). Two mutations in codons 12 and 61 coexisted in one tumor, which were found to be present in different Ha-ras alleles. The incidence of Ha-ras gene mutations were similar in groups treated with (3 of 6) or without (3 of 8) sodium saccharin. These results suggest the involvement of activated Ha-ras gene in rat urinary bladder carcinogenesis induced by FANFT. PMID- 2206285 TI - DNA sequence analysis of gamma radiation-induced deletions and insertions at the APRT locus of hamster cells. AB - Gamma radiation-induced gene rearrangements at the Chinese hamster ovary cell locus coding for the purine salvage enzyme adenine phosphoribosyl transferase (APRT) consist of both simple deletions and more complex alterations that are presumably the result of multiple strand breaks. To characterize these mutations at the DNA sequence level, fragments altered by deletion and insertion mutations were obtained by cloning in lambda phage vectors or by using the polymerase chain reaction. The radiation-induced deletions characterized here eliminate 3-4 kb and have at least one breakpoint in an AT-rich region or near short direct or inverted repeats. Insertions involve small fragments (102 and 456 bp) of repetitive DNA that appear to be related to B2 (short interspersed repetitive) and long interspersed repeat families. The novel fragments bear little resemblance to each other or to sequences at the integration sites, and their introduction is accompanied by a small target site deletion. PMID- 2206286 TI - [Genetics and reproduction. 28th meeting of the French Society for the Study of Fertility. Paris, 19-21 October 1989. Proceedings]. PMID- 2206287 TI - [Current status of reproduction control in France]. AB - Fertility declined rapidly in France between 1965 and 1976, mainly because of a decrease in the number of births of parity 3 or more. This change was due to both a decline in the desire for children and to a large reduction in the number of unwanted births. The INED national survey of 1988 showed a rapid spread of medical contraceptive techniques (pill and IUD) since 1965. In the same survey, a significant proportion of women reported difficulties in conceiving: these difficulties resulted in a much longer time-interval before conception; in addition women tended to become more and more impatient in this regard. PMID- 2206288 TI - [Consequences of abnormalities of chromosome structure in domestic animals]. AB - Abnormalities in chromosome structure generally have no phenotypic expression but are very often associated with reproductive disorders. In cattle, sheep and goats, the robertsonian translocation seems to be the most frequent abnormality of chromosome structure. In the pig, reciprocal translocations are very common. The accumulation of data on the frequency of such abnormalities and their effects on reproductive performance prompted an evaluation of their economic consequences in cattle and pigs. In cattle, because of the negative effect of 1/29 translocation, an eradication program, based on the removal of carrier bulls from artificial insemination centers was established. In pig, the main effect of the reciprocal translocations was a reduction in the number of offspring, up to 50%, thus representing a considerable economic loss. PMID- 2206289 TI - [Diagnosis of the sex of bovine embryos using molecular biology]. AB - Thanks to a bovine genomic library enriched with Y chromosome-specific sequences, a probe specific to this chromosome of genera Bos and Bison and repeated on about 2,000 copies in the male genome was isolated. To be compatible with embryo transfer and/or freezing, sex determination has to be done on a 10-20 cell embryo biopsy from a day-7 bovine blastocyst. The in situ hybridization with biotinylated BC 1.2 probe and immunocytochemical revelation permitted the visualization of the hybridization signal on the nucleus of each cell. Because of the numerous steps required, this technique was difficult to apply routinely. For that reason we worked out the polymerase chain reaction technique. From the BC 1.2 sequence, we determined several oligonucleotide primers and probes with the aim of amplifying the Y chromosome-specific sequences. This technique, which is easy to perform and to automate, enabled us to obtain a strong male-specific hybridization signal on genomic DNA and embryo cells. PMID- 2206290 TI - [Medical aspects of diagnosis before implantation]. AB - With the currently available techniques, it is not possible to perform cytogenetic and enzymatic analyses on 1 or 2 cells collected from a human embryo prior to its reimplantation. The recent techniques of polymerase chain reaction may allow DNA analyses in some cases: sexing or diagnosis of monogenic diseases. The reliability of these techniques and the absence of adverse effects due to embryo micromanipulation have to be demonstrated. The practical medical application of preimplantation diagnosis requires in vitro fertilization in a fertile couple and its low rate of success has to be compared to the reliability of the early prenatal diagnosis on chorionic villus samples. PMID- 2206291 TI - [Clinical approach to prenatal diagnosis of chromosome abnormalities]. AB - In the case of prenatal diagnosis of chromosomal aberrations, the obstetrician has to determine the high risk situation for which a fetal karyotype examination has to be done. Before pregnancy, the karyotyping indications are defined by genetic consultation in order to analyze classical data such as the parents' age, repeated spontaneous abortions, previous child with a genetic defect, fetal malformations or intrauterine death... During pregnancy, clinical warning signs, in particular, anomalies in the amniotic fluid and fetal growth retardation should be recognized, but most abnormal karyotypes are detected by ultrasonographic examination (average: 11.3%). Down's syndrome diagnosis is presently evaluated by some more specific ultrasonographic signs such as fetal nape or femur length measurements and by new biological parameters such as hCG assay. The sampling method for karyotyping, early or late amniocentesis, first trimester but also second and third trimester placental biopsy or cordocentesis will be chosen in accordance with the importance of the chromosomal aberration expected, gestational age, procedure complication risks and the obstetrician's experience. The following examinations could be proposed: in high risk cases determined before pregnancy, a chorionic villus sampling should be done between the 9th and 11th weeks of gestation; in low risk cases such as advanced maternal age, a first trimester chorionic villus sampling or a second trimester amniocentesis could be chosen; in the case of Down's syndrome, warning signs, for example ultrasonographic or biological parameters, a second trimester placental biopsy to relieve the parents' anxiety; in high risk cases such as ultrasonographic malformations, late placental biopsy or cordocentesis. PMID- 2206292 TI - [The Y chromosome and sex determination]. AB - The structure and function of the human Y chromosome have been approached by molecular genetics. The use of Y-derived DNA probes to analyze the Y chromosome of patients with sexual differentiation abnormalities allowed the construction of a deletion map localizing TDF (testis determining factor) in the terminal part of the short arm. These studies culminated recently in the isolation of a candidate gene for the TDF locus. Nevertheless, the existence of a related locus on the X chromosome does not fit with the simple hypothesis of a single Y-located gene for testis differentiation. The finding of a strictly homologous region at the tip of the short arms of X and Y chromosomes allowed the characterization of another major property of the sex chromosomes. These so called pseudoautosomal DNA sequences show only a partial sex linkage and can be exchanged between X and Y chromosomes during male meiosis. Genetic analysis and determination of the physical length of the pseudoautosomal region show that it is subjected in male meiosis, to a recombination rate about 20 times higher than the mean value of the human genome. In 1966, Ferguson-Smith proposed that an abnormal cross-over was responsible for both types of sex inversions in humans: XX males and XY females. Segregation analysis of the pseudoautosomal loci in these patients has demonstrated the validity of this hypothesis and shown the existence of sex inversions unrelated to the TDF locus. The construction of a detailed map of the human Y chromosome enables the search for new genes (H-Y antigen, fertility gene(s]. The finding of several homologous regions on the sex chromosomes confirms the hypothesis of a common origin and should help to understand the establishment of sex determination and X inactivation mechanisms during mammalian evolution. PMID- 2206293 TI - [Intersexuality in domestic mammals]. AB - With the exception of bovine freemartinism, intersexuality is rarely reported in domestic animals. The few cases of intersexuality reported here in dogs, cattle, goats, sheep and horses were classified according to the karyotype. The XX intersexes described here included goats which were either polled male pseudohermaphrodites or true hermaphrodites and dogs which were female pseudohermaphrodites. Among the XY intersexes studied, one dog was a true hermaphrodite, whereas the others were male pseudohermaphrodites, all mares showed gonadal dysgenesis and one cow was a female pseudohermaphrodite. XX/XY intersexes were detected in ovine cases of freemartinism. PMID- 2206294 TI - The role of chromosome abnormalities in reproductive failure. AB - The frequency of chromosome abnormalities in spontaneous abortions, stillbirths, livebirths and among all clinically recognized pregnancies is given. Data on the parental origin of sex chromosome abnormalities and certain autosomal trisomies determined using molecular probes are presented and the proportion of sperm and eggs that are nullisomic or disomic for a sex chromosome to an autosome 16, 18 or 21 is calculated. PMID- 2206295 TI - [Chromosome abnormalities of human gametes]. AB - Human newborns carrying chromosomal abnormalities are the survivors of a considerably larger cohort of affected conceptions. A direct cytogenetic study of these conceptuses would imply their destruction. Moreover, the ability to determine the parental origin of an additional or missing chromosome is limited from a methodological point of view. The cytogenetic study of human gametes provides information on these mechanisms. Several large-scale studies on sperm complements of normal men give an estimated abnormality rate of 10%. Our results concerning four carriers of reciprocal translocations show no evidence for a selection against abnormal sperm. Since about 30% of the recovered eggs fail to become fertilized in IVF programs, human oocytes have become available for large cytogenetic studies. Analysis of oocytes II provides information on the first meiotic non-disjunction rate. In our sample of 405 karyotypes, the rate of aneuploidy was 27%. No relationship was established between this frequency and the mode of stimulation of ovulation. No increase was observed with maternal aging. PMID- 2206296 TI - [Chromosome abnormalities of the fertilized human egg]. AB - In vitro fertilization enabled the study of lethal (parthenogenesis) or sublethal (triploidy, monosomy and trisomy) chromosomal abnormalities in man. According to the literature, 23 to 71% of preimplantation embryos carry a chromosomal defect. Various factors, such as delayed fertilization, early embryo fragmentation or elevated maternal age (greater than 35 years) are related to an increase in the incidence of chromosomal aberrations. These data reinforce the debate on a preimplantation genetic diagnosis in order to select for transfer only viable and apparently normal embryos. PMID- 2206297 TI - [Morphological aspects of lethal chromosome errors]. AB - Correlations have been established between phenotype and karyotype in spontaneously aborted specimens. The criteria used to determine the phenotype were based on estimated developmental age and macroscopic examination of embryo and placenta, taking into account the morphological modifications due to in utero retention. The probability that a chromosomal aberration was the cause of the abortion is high when the developmental arrest occurred before 5-6 weeks and the expulsion was delayed. The frequency could be estimated at 75% when the developmental arrest was at 2-3 weeks, and 65% when the developmental stage reached 5-6 weeks. Main anatomical features are described permitting an attempt to assign the type of chromosomal anomaly by ultrasonographic examination. PMID- 2206299 TI - [Influence of the nitrogen from the parietal constituents on the in sacco degradability of feed nitrogen]. AB - In sacco nitrogen (N) degradability values (DT) of 36 feeds were correlated with the N solubility or the N fractions present in the neutral and acid detergent fiber residues (NDF, ADF). Moreover, combinations of these parameters improved the prediction of the undegradable N fraction (RSD = 6.9). PMID- 2206298 TI - [Incidence of structural chromosomal abnormalities in spermatogenesis in man]. AB - Infertility due to gametogenic failure is frequently associated with structural autosomal abnormalities. Recent meiotic studies at the pachytene stage undertaken in human infertile heterozygous carriers for such rearrangements have regularly shown a synaptic failure around the breakpoints, an association of the translocation figure with the sex chromosomes and the frequent involvement of the acrocentric chromosomes. Two main models were proposed to explain the male sterilizing effect of autosomal rearrangements: the impairment of spermatogenesis could be the result of: 1) the XY-autosome interaction; 2) the pairing disruption around the breakpoints at the pachytene stage. They could contribute significantly to germ-cell atresia. PMID- 2206300 TI - [Influence of the type of feed on the significance of particle loss in the measurement of in sacco degradability of feed nitrogen]. AB - In sacco dry matter (DM) and nitrogen (N) disappearances without degradation (ie, lost as particles) were measured in 18 concentrates. Mean losses were 17% DM and 11% N, but were larger with oats (40 and 32%). They led to a mean overestimation of N degradability by 3.4 points. Overestimation was higher (up to 8 points) when the losses were high, as for oats, or when degradability was low, as for fish meal. PMID- 2206301 TI - [Influence of the drying method and the grinding fineness of the sample forage on the determination of nitrogen degradability in the rumen]. AB - The effects of the drying method (freeze-drying, forced-air oven at 60 degrees C for 24 h and conventional oven at 80 degrees C for 48 h) and grinder screen size (0.8 vs 1.5 mm) upon in sacco degradability were compared with 7 forages. Nitrogen degradability was reduced by oven drying even at the lower temperature, but screen size was less important. PMID- 2206302 TI - [In sacco degradability of grass silage and bacterial contamination of residues]. AB - The in sacco degradability of wilted grass silage, harvested at 2 stages of maturity, and of direct cut silage was determined in 6 heifers. The date of cutting had a pronounced effect on ruminal degradation and bacterial contamination of the feed residues. On the contrary, wilting of the grass prior to ensiling did not influence these parameters. PMID- 2206303 TI - Investigation using zero time t0 to compute protein rumen degradability (DT). PMID- 2206304 TI - [Influence of the conditioning method of a green forage on its chemical composition, the in vitro digestibility of the organic matter and the in sacco degradability of nitrogen in the rumen]. AB - Fiber contents of oven-dried ray-grass cut at different stages of maturity were higher than the values obtained for freeze-dried samples. The reverse was observed for in vitro organic matter digestibility. Moreover, oven-drying dramatically decreased in sacco nitrogen degradability as compared to lyophilization, preservation by freezing with liquid nitrogen and use of fresh material. PMID- 2206305 TI - [Degradability in small bags of nitrogenous components of feed concentrates: standardization of the method and intra- and interlaboratory variability]. AB - In sacco degradability of feed protein (DT) was measured in 13 feedstuffs by 4 laboratories according the French standardized procedure. Adjustment for variations in microbial activity by reference to DM disappearance of a standard sample of lucerne decreased within and between lab variability. When the standardized procedure was carefully followed, results were in rather good agreement between labs. PMID- 2206306 TI - [Relationship of nitrogen degradability of feed concentrates in the rumen and its digestibility in the intestine, and several biochemical criteria]. AB - Estimation of intestinal nitrogen digestibility was related to acid detergent insoluble nitrogen (ADIN) or pepsin-insoluble nitrogen (IP). Feedstuffs were then classified according to their in sacco nitrogen degradability in the rumen and ADIN or IP. PMID- 2206307 TI - Adaptation of the free bag technique to evaluate the use of the nitrogenous component of feeds in the large intestine of the pony. PMID- 2206308 TI - Study of the potential of near-infrared reflectance spectroscopy in the analysis of the tree foliage intake of goats. PMID- 2206309 TI - [Chemical composition of feces from bovines, sheep and goats feeding from Sahelo Sudanese natural or farming fields: its use for estimating the nutritive value of their diet]. AB - The chemical composition of grazing cattle, sheep and goat feces is described according to animal species, type of range (natural pasture or fields after crops) and season in a sub-Sahelian environment. Nutritive value (organic matter digestibility and digestible crude protein) of forages can be estimated from some chemical fecal criteria. PMID- 2206310 TI - [Additivity of in sacco degradation of dry matter from simple mixtures of feed concentrates]. AB - Barley and maize were combined with either lupine seeds or corn gluten meal so that the 4 blends present different rumen degradation rates for their carbohydrate and/or nitrogen constituents. The measured values (dm) of dry matter in sacco degradability of these concentrates were higher before and lower after 8 h of incubation compared to the calculated values of degradability (dc) obtained by the additive method according to their composition. Moreover, the differences (dm-dc) were the highest for the less degradable feeds. PMID- 2206311 TI - [Effects of extrusion of peas (Pisum sativum) on the intestinal flow of nitrogen in cows]. AB - Six Friesian heifers fed a 40% pea diet were used in a cross-over design. Ground and extruded peas were compared. Decreased nitrogen (N) solubility produced by extrusion was associated with an increase in non-ammonia-N flow (+ 36%; P less than 0.001) resulting from improvements in bacterial N flow (+ 53%; P less than 0.01) and in feed N flow (+ 19%; P greater than 0.05). PMID- 2206312 TI - Effects of the treatment of straw with NaOH and urea solutions on ingestibility and digestibility in sheep. PMID- 2206313 TI - Ammoniation of straw by urea: extent of ureolysis and improvement of nutritive value with moderate water addition. PMID- 2206314 TI - Ammoniation of straw by urea: influence of addition of soybeans and/or molasses on characteristics of treatment. PMID- 2206315 TI - Image analysis of the size and morphological characteristics of ruminal digesta particles from sheep fed mixed-grass hay. PMID- 2206316 TI - [Measurement of the flow of reticular content in cows]. PMID- 2206317 TI - [Changes in fermentation in the rumen and in levels of blood insulin induced by separated ingestion of nitrogenous supplement and forage in dry cows: preliminary results]. PMID- 2206318 TI - [Comparison of different adjustment models of curves of fecal excretion of transit markers]. AB - Seventy nine fecal excretion curves of rare earth were adjusted with 3 published models (Grovum and Williams, 1973; Dhanoa et al, 1985; Siddons et al, 1983). The models provided statistically similar estimations of particulate turnover in the first compartment and mean retention time. However, some important individual differences between parameter values could be observed from one model to another. PMID- 2206320 TI - [Water dynamics in the rumen of dairy cows: variation factors and relationship with particle transit]. AB - Dilution rate and volume of water in the rumen varied between rations and dairy cows but were independent of the feed intake level. Correlations between rates of transit of liquid and particles were poor. PMID- 2206319 TI - [Effects of the addition of iso-acids to feed on ruminal fermentation, in sacco degradation of dry matter and the concentration of several blood parameters in cows]. AB - Three rumen-fistulated cows fed maize silage and concentrates were supplemented with either soybean oil meal or urea, associated or not with isoacids. The isoacids increased the volatile fatty acid concentration, lowered the ruminal ammonia concentration and in sacco dry matter disappearance and did not influence blood parameters. PMID- 2206322 TI - Ruminal hydrolysis of dietary triglycerides in dairy cows fed lipid-supplemented diets. PMID- 2206321 TI - [Influence of the quantity of ingested dry matter and food retention time on feed digestibility in dairy goats]. AB - Simultaneous measurements of organic matter digestibility (OMD) and particulate mean retention time (MRT) of diets containing various proportions of hay and concentrate (bran or beet pulp) were performed in lactating or dry goats. Beyond the hay and concentrate influences, the OMD decreased by 0.5 and 1.3 points as the dry matter intake level increased by 10 g/kg LW0.75 and MRT decreased by 5 h, respectively. PMID- 2206324 TI - [Minimal requirement of phosphorus for maintenance in lambs]. AB - The purpose of the present study was to determine the minimum level of endogenous fecal loss of P in sheep receiving a P-deficient and Ca-rich diet composed of natural feedstuffs. The low fecal endogenous loss of P (15 mg/kg/d) was obtained under abnormal physiological conditions and did not correspond to the minimum requirement for maintenance. PMID- 2206323 TI - Relationship between intake and duodenal flows of linoleic acid in dairy cows fed lipid-supplemented diets. PMID- 2206325 TI - Comparison of the chemical composition and the particle size of alimentary bolus in goats and sheep fed various diets. PMID- 2206326 TI - A comparison between the digestibility of hay by donkeys and ponies. PMID- 2206327 TI - Comparison of the hydrolytic activity of microorganisms in the forestomachs of dromedaries and sheep. PMID- 2206328 TI - Digestion of allergenic soya protein in the preruminant calf. PMID- 2206329 TI - [Digestion of pea proteins in the abomasum and the small intestine in preruminant calves: preliminary results]. AB - In preruminant calves given a milk-substitute diet containing raw pea flour, the amounts of immunoreactive legumin leaving the abomasum and the ileum were found to be equivalent to about 24 and 3% of intake, respectively. This long-term presence along the digestive tract could favor its allergenic effects. PMID- 2206330 TI - [Study using lectins of the parietal polysaccharides of Sphaeromonas communis]. AB - Using fluorescein isothiocyanate-labeled lectins of various specificities, differences in the cell wall polysaccharide composition among the different parts of the thallus and during the cycle of S communis were demonstrated. PMID- 2206331 TI - [Use of glucose and cellobiose by 3 strains of Fibrobacter succinogenes]. AB - F succinogenes strains S85, 128 and 095 were compared with respect to their growth using glucose and/or cellobiose as the carbon and energy substrate(s) and their capacities to degrade cellulose. The growth rate of F succinogenes strain S85 was the same using glucose or cellobiose, whereas the growth rates of strains 128 and 095 were about thrice the rate when using cellobiose. Strain S85 could simultaneously use glucose and cellobiose, while strains 128 and 095 tended to use preferentially glucose then cellobiose in a mixture of the 2 sugars. Their capacities to degrade cellulose were equivalent. PMID- 2206332 TI - [O-demethylation and metabolism of the methoxyl group of vanillic acid, monomer model of lignin, by the rumen bacterium Syntrophococcus sucromutans]. AB - The O-demethylation of a lignin monomer by washed cells of the rumen bacterium S sucromutans was studied using chemically synthesized O-[methyl-14C]vanillate. During cometabolism of pyruvate and vanillate, the label from the methoxyl group was incorporated into acetate, the sole product, which was singly labeled in the methyl group. PMID- 2206333 TI - A comparison of two ways of expressing the voluntary intake of oak foliage-based diets by goats raised on rangelands. PMID- 2206334 TI - [Consumption of ligneous resources at an oak coppice by sheep in the summer]. AB - In a coppice, under conditions of low grass availability and high stocking rate (300 ewes.ha-1) the time spent eating bushes reaches 60% of grazing time and increases with flock size (stocking rates of 50 ewes.ha-1 vs 150 ewes.ha-1). PMID- 2206335 TI - [Quantitative analysis of the rythm of feeding and merycismal activities]. AB - The nycterohemeral eating and ruminating patients were studied in 6 heifers given ad libitum access to grass or corn silage in a 2 period cross-over design. Rhythm components (no of cycles/24 h) were characterized by the finite Fourier transform of hourly means of the 24 h mastication activities. Rhythm components 1, 3 and 4 contributed considerably to explaining the total dispersion of 24 h eating and ruminating mastication series. PMID- 2206336 TI - [Botanical composition of food of domestic ruminants feeding from Senegalese farming fields using a histologic analysis of the feces: effect of the technique of preservation and centrifugation of feces]. AB - During a microhistological study of feces from domestic ruminants (cattle, sheep, goats), centrifugation was used to increase from 11 (classic method) to 93% the rate of dicotyledon epidermis in the total particles of the suspension. Regardless of the conservation method used (drying or addition of salt, formol or ethanol), a better analysis of the dicotyledon part of the diet was obtained. PMID- 2206337 TI - [Effects of infusions of a complete mixture of volatile fatty acids during a meal on the food intake of dry or lactating cows]. AB - Infusions of 3 or 6 mol of a volatile fatty acid mixture into the rumen for 3 h during the morning feeding depress feed intake of lactating dairy cows (1.5 kg of dry matter (DM)) and, to a lesser extent, that of dry cows (0.8 kg DM). These differences occur between 1 and 3 h after the beginning of the meal and are not recovered over the day. PMID- 2206338 TI - Selective vagal influences at the gastroduodenal junction in sheep. PMID- 2206339 TI - Central and peripheral beta-adrenergic control of gastrointestinal motility in sheep. PMID- 2206340 TI - [Effect of vasopressin on the motor profile of the reticulum and rumen in sheep]. AB - Intravenous injections of lysine-vasopressin into sheep inhibited rumino reticular phasic contractions and electric activity. Sometimes, a rapid electric pattern was observed and persisted even after reappearance of normal phasic contractions. PMID- 2206341 TI - [Effect of hypoxia on plasma concentrations of gastrin and gastric inhibitory polypeptide (GIP) in newborn calves]. AB - Calves were subjected to experimental hypoxia from 0.5 to 4 h after birth. The plasma level of immunoreactive gastric inhibitory polypeptide was higher (P less than 0.05) than in control calves during hypoxia and 2 and 7 h later. However, the gastrin level was not lower during treatment and was higher (P less than 0.05) 3, 6, and 13 h later. Hypoxia could have changed circulating levels or degradation rates of these peptides and could have delayed abomasal emptying. PMID- 2206342 TI - [Modulation of pancreatic chymotrypsin messenger RNA during post-natal development and weaning in calves]. AB - Levels of chymotrypsin mRNA in the pancreatic tissue of preruminant calves were significantly decreased on d 28 and to a lesser extent on d 119 as compared to those of newborns. Enzymic activity regularly increased during the same period. By contrast, both chymotrypsin-specific activity and the mRNA level in the ruminant animals were enhanced on d 119 (1.4- and 2.3-fold, respectively), suggesting that some pretranslational regulation of the chymotrypsin gene was induced by weaning. PMID- 2206343 TI - [Weight characteristics of digestive tissues and contents of weaned calves, in the case of 2 feed concentrates differing in the nature of nitrogenous components]. AB - Feeding dairy calves for 13 weeks on concentrate diets differing in nitrogen degradability (pea vs soya bean meal) did not affect the fresh weight of digestive tissues and digesta at a slaughter age of 20 wk. PMID- 2206344 TI - [Relationship of the level of energy ingestion and several blood parameters in kids during 2 weeks after weaning]. AB - Eighteen male kids were fed ad libitum hay and concentrate from weaning at 4, 6 or 8 wk of age. Metabolizable energy intake/kg of live weight 0.75 was more closely related to beta-hydroxybutyrate than to non-esterified fatty acids or glycemia during the first post-weaning wk, but it was the contrary during the next one. PMID- 2206345 TI - Importance of the portal venous pathway to the transport of intestinal triglyceride-rich lipoproteins in the preruminant calf. PMID- 2206346 TI - Effects of rapeseed oil duodenal infusion on dairy cow performances and blood metabolites during early lactation. PMID- 2206347 TI - Effects of rapeseed oil duodenal infusion on adipose tissue lipolytic activities of dairy cows during early lactation. PMID- 2206348 TI - Net energy value of rapeseed oil infused into the duodenum of lactating cows. PMID- 2206349 TI - [Changes in liver mono-oxygenases in function of age in sheep of Lacaune breed]. PMID- 2206350 TI - [Metabolism of ethanol in sheep]. AB - Ethanol metabolism in the sheep was investigated using bolus and constant infusion techniques. Mean half-life of ethanol was 155 min. Ethanol infusion induced a 2-3-fold increase in plasma acetate and propionate levels and a small delayed decrease in that of plasma glucose. PMID- 2206351 TI - [Renal plasma flow and glomerular filtration in conscious sheep: effect of a free protein diet]. AB - In conscious sheep fed a low protein diet, the urinary flow rate and glomerular filtration rate were reduced. This reduction was not linked to a low blood urea level. PMID- 2206352 TI - [Combined effects of injected 1-29 GRF and diet energy level in lactating goats]. AB - Subcutaneous injections of 1-29 GRF and diet energy level were studied in 48 dairy goats using a 2 x 2 factorial design. Energy and GRF effects were additive on milk production and some interactions were observed on the milk fat and protein contents. Subcutaneous injections seemed to be less efficient in promoting milk secretion than the intravenous route used in a previous trial. PMID- 2206353 TI - [Mathematical model of daily increase of lipids and proteins in bovines]. AB - A mathematical model for predicting body gain composition of cattle is presented. Daily lipid, protein or tissue gains are predicted according to body weight and body weight gain, for male or female cattle of various breeds. The aim and the biological basis of this model are described. PMID- 2206355 TI - [Use of urea as a marker of body water in Friesian cows]. AB - Urea was used as a marker body water. Twelve catheterized dairy cows were injected with urea for 3 consecutive days. Equilibrium between injected and endogenous urea was obtained at 35.9 min over the 3 d. Different models to estimate urea space (EU) were compared with body water estimated at slaughter. The standard error was minimum when using the mean of EU on the 3 daily estimates obtained at 20 min. However, repeatability of EU measurement was low. PMID- 2206354 TI - [Effect of the combination of estradiol-17 beta and trenbolone acetate on the plasma concentration of various metabolites and hormones in kids before a meal]. AB - A combined implant of 17 beta-estradiol trenbolone acetate in young male goats decreased blood glucose and insulin 28 d after treatment, but had no effect on growth or thyroid hormones. No relation was found between hormonal concentrations and growth performance. PMID- 2206356 TI - [Use of urea diffusion space for the in vivo prediction of body water in milk-fed kids]. AB - Urea dilution space (EU) calculated by a 2 open compartment model was found to be much larger than empty (EBW) or total body water (TBW) in milk-fed kids. Estimate of EBW with EU was less accurate than with body weight (RSD = 666 vs 197 g). When body weight was used as an additional covariate with EU, prediction of EBW was slightly improved (RSD = 180 g). PMID- 2206357 TI - [In vivo estimation of body lipid content of lactating goats based on the heavy water or the urea methods]. AB - Body lipid content of 12 dairy goats was predicted with deuterium oxide (D2O) or urea space (US). With the urea method, lipid prediction was better than with live weight alone (RSD: 1.73 kg vs 2.66 kg) but about half as accurate as with the D2O method (RSD: 0.84 kg). PMID- 2206359 TI - Learned helplessness in elderly hospitalized patients. PMID- 2206358 TI - [Estimation of the lipid content of lactating goats using various methods which give information about lipid metabolism or body status]. AB - In 10 lacating goats, the body condition score was well correlated (r = from 0.80 to 0.83) to the empty body lipid content measured chemically after slaughtering. A good evaluation (r = 0.83) can be obtained from the total fatty acid content of oleic acid in milk. PMID- 2206360 TI - Cancer chemotherapy in the elderly patient. AB - The elderly oncology patient has unique needs that require consideration in all aspects of care, from drug administration to nursing management. Aging is a highly individualized process and may present as a variety of clinical manifestations. As these age-related changes occur the oncology nurse must be prepared to recognize their potential impact on cancer treatment for each individual patient. To intervene successfully requires the knowledge and application of both geriatric and oncology nursing principles. PMID- 2206362 TI - Cancer in the elderly. PMID- 2206361 TI - Untangling the knot: assessment and preventive care of the elderly person. PMID- 2206363 TI - Providing skilled care with a rehabilitation focus for the elderly: a health care dilemma. PMID- 2206364 TI - Self-care issues for the elderly. PMID- 2206365 TI - The insulin-dependent diabetic as a model for pain management. PMID- 2206366 TI - Delirium in elderly cancer patients: nursing management. AB - Delirium is a syndrome that requires immediate medical and nursing attention. Systematic and regular assessment of specific mental status factors is necessary for early identification of the signs and symptoms of delirium. Nurses are with patients around the clock and thus are in an optimal position to assess the patients' mental status and to provide the physical, psychological, and social support they need. Nurses can have a significant effect on this problem, with early detection and appropriate management helping to ensure safety and minimize the emotional stress this syndrome can cause. PMID- 2206367 TI - Overview of aging. AB - The care of elderly persons involves complex assessments by educated and caring health providers. It requires sensitivity, gentleness, hard work, and patience. Those difficulties are offset, however, by the satisfaction gained from learning about the unique people we care for and from helping them cope with their illness. PMID- 2206368 TI - [Identification methods of mineral drugs]. AB - This paper recommends thirteen methods for identifying mineral drugs on the basis of their physical characteristics and chemical properties. An identification table of popular mineral drugs is given. PMID- 2206369 TI - [Microscopic identification of semen Cuscutae]. PMID- 2206370 TI - [Biological characteristics of Psoralea corylifolia L]. AB - A study has been made on the biological characteristics of Psoralea corylifolia under general cultivating conditions. To search for the laws of growth and development so as to facilitate further studies on the cultivating techniques for higher production of Psoralea corylifolia. PMID- 2206371 TI - [Influence of processing on trace elements in traditional Chinese drugs]. AB - By comparing the contents of nine trace elements in fourteen Chinese drugs (including thirty-six samples) before and after processing, this experiment was carried out primarily in search of the ways in which bears on trace element contents, so as to help improve the quality of processed drugs. PMID- 2206372 TI - [Pharmacological action of various processed Mylabris phalerata Pallas]. AB - We have compared the acute toxicity, sub-acute toxicity and in vitro and in vivo anti-tumor action of the rude drug, stir-fried with rice, and alkali-processed drugs of Mylabris phalerata before and after removing the head, feet and wings. The results indicate that the toxicity of the processed drugs is lower than that of the rude ones; the toxicity becomes higher without head, feet, and wings; and the alkali-processing method is better than stir-frying with rice recorded in the pharmacopeia. PMID- 2206373 TI - [Stability examination of the inclusion compounds of 8 Chinese medicinal volatile oils with beta-cyclodextrin]. AB - The content, hence the stability of volatile oils and their main components in the inclusion compounds of 8 Chinese medicinal volatile oils with beta cyclodextrin have been examined with different storage times. The 8 Chinese medicines are Vitex negundo var. heterophylla, Notopterygium incisum, Alpinia officinarum, Atractylodes lancea, Pogostenon cablin, Asarum heterotropoides var. mandshuricum, Schizonepeta tenuifolia and Amomum villosum. PMID- 2206374 TI - [Chemical constituents of the seed oil of Astragalus complanatus R. Brown]. AB - beta-sitosterol and fatty acids were obtained from the oil of seeds of Astragalus complanatus. The fatty acids were separated and their molecular weights determined by GC-MS. Fourteen of them were identified as heptenoic acid, tetradecanoic acid, pentadecanoic acid, hexadecanoic acid, octadecenoic acid, octadecanoic acid, octadecadienoic acid, linolenic acid, eicosanoic acid, eicosenoic acid and docosanoic acid, etc. PMID- 2206375 TI - [Determination of micro amounts of zinc in medicinal herbs using the chemiluminescence quenching method]. AB - This paper is based on the principle that the relative luminous strength of luminol-H2O2-Co2+ chemiluminescence quenching is extinguished by zinc. The contents of zinc in Flos Carthami, Radix Codonopsis Pilosulae, Radix Ginseng and Fructus Lycii were measured in optimol experimental conditions. PMID- 2206376 TI - [Effects of tetrandrine on platelet aggregation, platelet adhesion and coagulation]. AB - We examined the effect of tetrandrine on platelet aggregation, platelet adhesion and coagulation in vitro. The results showed that tetrandrine markedly inhibited the platelet aggregation induced by ADP or collagen. Tetrandrine also markedly inhibited platelet adhesion and thrombosis, but didn't change thrombin coagulation time and plasma coagulation time obviously. PMID- 2206377 TI - [Analgesic and anti-inflammatory effects and toxicity of houjianxi]. AB - It is effective for acute and chronic laryngopharyngitis clinically. Houjianxi can raise the pain thresholds during hot-plate test in mice, tail flick test in rats, and writhing test in mice with single dose ig 0.125 to 2.0 g/kg. Houjianxi can also inhibit the swelling of hind paw induced by sc 1% carrageenin 0.1 ml in rats as well as the increased vascular permeability induced by ip 0.7% HAC in mice. Toxic side effects were not observed for Houjianxi ig 48 g/kg x 3 within a day in mice and 1.8 g/kg daily for 90 d in rats. PMID- 2206378 TI - [Effect of wuwei chongji on the mechanical activity of the stomach of SD rats in vivo]. AB - The effect of Wuwei Chongji on the mechanical activity of stomach of SD rats was studied using fixed point method. The experimental results showed that Wuwei Chongji increased the amplitude and frequency of contraction of stomach in rats, and was able to adjust the high and low tension of contraction of stomach. The contraction of the stomach was not influenced by Natrii Chloridi (0.9%) at the same dose. PMID- 2206379 TI - [Inhibitory effect of yunfujing on vestibular stimulative response in rats and volunteers]. AB - Fifty female rats were used in the experiment. With rotation model, Yunfujing was shown to inhibit nystagmic response of rats. The inhibitory effect was 20-30 times stronger than that of Mihuanjun. In Coriolis test, the tolerance time of vestibular stimulative response was taken as a parameter for judging drug efficacy in 32 male volunteers. Following oral administration of Yunfujing at a dose of 400 mg, the tolerance time of vestibular stimulative response was prolonged significantly from 411.34 to 759.63 s. In the mean time, no changes of blood pressure and pulse were observed in the treated group. PMID- 2206380 TI - [Review of adverse effects of drugs in 54 titles published in the China journal of Chinese Materia Medica]. PMID- 2206381 TI - [Application of cluster analysis of the study of commodity bulbus Lilii (I)]. AB - Cluster analysis has been applied to the classification of various commodities of Bulbus Lilii in order to sort out the main one. The stomatic index of the commodity has been determined. PMID- 2206383 TI - [Determination of primary metabolic products of fungi promoting seed germination of Gastrodia elata Bl. and other Orchidaceae medicinal plants]. AB - The contents of amino acids, protein, water-soluble sugar, reducing sugar and microelements in seven strains of seed-germination-promoting fungi were determined. It was found that the contents of primary products were different in these fungi. In the light of physiological characteristics of seed germination, the action mechanism of the products in promoting seed germination was discussed. PMID- 2206382 TI - [plants of Coptis from Tibet and Yunnan]. AB - In this paper the relationship of Tibetan Huanglian and Yunnan Huanglian with Coptis teeta has been studied. The distribution and taxonomic features of Tibetan Huanglian are just the same as Coptis teeta, but quite different from Yunnan Huanglian. The results reveal that Tibetan Huanglian and Yunnan Huanglian are different in botanical origin. PMID- 2206385 TI - [A processing study of herba Cistanches]. AB - The synthetic rate of DNA in the liver and spleen and metallic microelements have been determined for the different preparations of Herba Cistanches. The results show that the salted Herba Cistanches in steamed from affects the synthetic rate of DNA in "Yang-Deficiency" animal models, with trace elements Zn, Mn, Cu, and Fe higher in content than other traditional preparations. PMID- 2206384 TI - [Quality standards of flos Sophorae Carbonisatus]. AB - The tannin and rutin contents in seventeen samples of Flos Sophorae Carbonisatus were determined. These samples were tested and examined microscopically, physically and chemically. Quality standards have been set forth for Flos Sophorae Carbonisatus. PMID- 2206386 TI - [Effect of disintegrating method on quantity extracted and constituents of essential oil in fructus Aurantii]. AB - The quantity extracted, constituents and their contents in essential oil from Fructus Aurantii were obviously influenced by the method of disintegration. Among stamp breaking in water, crusher-run and miling, stamp breaking in water is the best method. The advantage of this method lies in higher percentage recovery of the oil and smaller loss in volatilization. PMID- 2206387 TI - [Spectrophotometric determination of micro-amounts of zinc in Gynostemma pentaphyllum (Thunb.) Makino]. AB - 1-(2-pyridylazo)-2-naphthol (PAN) and Emulsifier OP have been used in the colorimetric determination of zinc in Gynostemma pentaphyllum. The results are in agreement with those of atomic absorption spectrophotometry. The method is simple, precise and rapid. The recovery is 97.8-103.7% and coefficient of variation is 1.4-4.6%. PMID- 2206388 TI - [Constituents of the seed coat of Arachis hypogaea L]. AB - From the seed coat of Arachis hypogaea two compounds were isolated. They were identified as the dimer of proanthocyanidin-A type(I) and D-(+)-catechin (II) on the basis of UV, IR, MS, CD, 1H-NMR, 13C-NMR and chemical evidences. It has been found that II is the effective constituent of this plant and I has some active effects as well. PMID- 2206389 TI - [Chemical constituents of Bupleurum Longicaule Wall. ex DC. var. giraldii Wolff]. AB - Five crystalline compounds were isolated from the whole plant of B. longicaule var. giraldii for the first time. Four of them were identified as rutin (I), narcissin (II, quercetin (II) and isorhamnetin (IV) respectively by means of chemical studies and spectrometric analysis. PMID- 2206390 TI - [HPTLC densitometric determination of free bile acids in bezoar]. AB - Cholic acid (CA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) which are extracted with CH3OH from Bezoar can be separated on HPTLC silica gel plate (made in China) with isooctane-n-butyl acetate-acetic acid (4:2:1), and the three bile acids were determined by TLC densitometry. PMID- 2206392 TI - [Anti-ulcer effects of weiteling tablets]. AB - The traditional Chinese medicine Weiteling Pain shows a marked anti-ulcer action when administered orally at a dose of 3g/kg. The drug has been found able to inhibit the formation of stress restraint induced ulcer and reserpine induced ulcer. A decrease of volume of gastric juice collected from pyloric ligated stomachs and a reduced level of gastric acid have also been observed. In addition, the drug can reduce the inflammatory reaction of the acute gastritis induced by salicylate. PMID- 2206391 TI - [A comparison of anti-arrhythmic effects of four kinds of rhizoma seu radix Nomopterygii]. AB - Experiments were conducted to compare the anti-arrhythmic effects of the four kinds of Qianghuo(Notopterygium incisum; N. forbesii; Pleurospermum rivulorum; Angelica silvestris). It has been found that all the four kinds of Qianghuo can antagonize arrhythmia induced by aconitine. Notopterygium incisum can prolong the ventricular vibration induced by CaCl2 and Pleurospermum rivulorum can prolong the ventricle stop induced by BaCl2. Thus Qianghuo can be used as a sedative and anti-arrhythmic drug. PMID- 2206393 TI - Molecular and antigenic analysis of treponemes. AB - The treponemes comprise the essentially non-cultivable Treponema pallidum subspecies (agents of syphilis, yaws and other human trepanematoses), the gut pathogen of pigs, T. hydysenteriae, and a group of antigenically related, cultivable species, some of which are strongly implicated in human periodontal or gastrointestinal disease. Technical developments during the last decade have made possible the molecular analysis of components of this diverse group of organisms. Polypeptides and other macromolecular components have been characterized by techniques including electron microscopy, gel electrophoresis and immunoblotting. Antigenic analysis has been greatly enhanced by the use of monoclonal antibodies. Finally, DNA cloning and genetic manipulation have enabled the detailed investigation of important antigens at a genetic, structural and functional level. We examine these developments and provide a current overview of the data now available, which is an important foundation for applications in diagnosis, therapy, and, potentially, immunization against disease. PMID- 2206394 TI - Staphylococcal and streptococcal pyrogenic toxins involved in toxic shock syndrome and related illnesses. AB - Toxic-shock syndrome (TSS) is an acute onset, multiorgan illness which resembles severe scarlet fever. The illness is caused by Staphylococcus aureus strains that express TSS toxin-1 (TSST-1), enterotoxin B, or enterotoxin C. TSST-1 is associated with menstrual TSS and approximately one-half of nonmenstrual cases; the other two toxins cause nonmenstrual cases, 47% and 3%, respectively. The three toxins are expressed in culture media under similar environmental conditions. These conditions may explain the association of certain tampons with menstrual TSS. Biochemically, the toxins are all relatively low molecular weight and fairly heat and protease stable. Enterotoxins B and C, share nearly 50% sequence homology with streptococcal scarlet fever toxin A; they share no homology with TSST-1 despite sharing numerous biological properties. Numerous animal models for development of TSS have suggested mechanisms of toxin action, though the exact molecular action is not known. The toxins are all potent pyrogens, induce T lymphocyte proliferation, requiring interleukin 1 release from macrophages, suppress immunoglobulin production, enhance endotoxin shock, and enhance hypersensitivity skin reactions. The genetic control of the toxins has been studied and suggests the exotoxins are variable traits. Some additional properties of TSS S. aureus which facilitate disease causation have been clarified. PMID- 2206396 TI - Choosing contrast media for pediatric gastrointestinal examinations. AB - The availability of the new low osmolality contrast agents during the last few years has necessitated a reconsideration of which is the most appropriate contrast agent to utilize in the gastrointestinal (GI) tract. There are some clinical situations in which these new agents have become the contrast media of choice (e.g., evaluation of suspected necrotizing enterocolitis, evaluation of suspected bowel perforation). There are many other clinical situations in which one needs to weigh the potential benefits of the new agents against significantly increased costs. This report reviews in detail the available contrast agents for studying the GI tract and outlines the advantages and disadvantages of each agent. The new agents are compared with existing agents such as barium and the hypertonic water soluble agents (e.g., gastrografin, hypaque, conray, etc.). Guidelines for the use of each agent are presented. PMID- 2206395 TI - The carbohydrate- and lipid-containing cell wall of mycobacteria, phenolic glycolipids: structure and immunological properties. AB - Phenolic glycolipids were first discovered as cell-wall constituents of M. bovis, M. bovis BCG, M. marinum, and M. kansasii. Recently, such compounds were also isolated from M. leprae and have been shown to be specific-species serological markers. Moreover, they seem to be involved, in the case of lepromatous leprosy, in the stimulation of the suppressor T-cells. The functional activities of these phenolic glycolipids over the immune cells stimulation emphasized the role played by these molecules in the mycobacteria pathogenicity. Phenolic glycolipids have also been found in M. gastri and M. tuberculosis strain Canetti. From a structural point of view, these glycolipids contain the same aglycon moiety mainly assigned to phenolphthiocerol diester while the sugar part structure confers to some of these glycolipids their antigenic specificity. The search of immunoreactive glycolipids and their function analysis remain a challenge for chemists and immunologists for the understanding of the mycobacteria pathogenicity. PMID- 2206397 TI - The temporal bone: imaging considerations. AB - CT and MRI have revolutionized the evaluation of the temporal bone and its diseases. Conventional polytomography, once the mainstay of clinical imaging, has now been completely replaced by CT for evaluation of the middle ear, ossicular chain, and otic capsule and by MRI for the study of the internal auditory canal, cerebellopontine angle, and brainstem. This article is an overview of these current methods and depicts normal and pathologic anatomy. The technical aspects and clinical indications for both modalities are discussed. PMID- 2206398 TI - Human placental protein 14 gene: sequence and characterization of a short duplication. AB - Differential hybridization of cDNAs corresponding to mRNAs expressed in the human endometrium during the secretory phase or during the first trimester of pregnancy, but not during the proliferative phase, allowed us to isolate and characterize cDNAs encoding human placental protein 14 (PP14). The cDNA was used to isolate the PP14 gene from a human genomic library. The entire gene encompasses 5.05 kb divided into seven exons by six introns. The human PP14 gene shows identical organization with the ovine beta-lactoglobulin gene, as expected from protein homology. Sequencing of 3 kb of the 5'-flanking region of the gene allowed us to characterize a 400-bp duplication of the PP14 gene lying at position -2,660. This duplication was homologous to 100 bp of exon 4 and 300 bp of intron 4, including 180 bp corresponding exactly to the right arm of an Alu element lying on the complementary strand. This homology suggests that this duplication may have arisen through a retroposition event. PMID- 2206399 TI - Stable expression of mouse Cyp1a1 and human CYP1A2 cDNAs transfected into mouse hepatoma cells lacking detectable P450 enzyme activity. AB - Using the mouse hepatoma Hepa-1c1c7 c37 mutant cell line that exhibits negligible benzo[a]pyrene hydroxylase (Cyp1a1) and acetanilide 4-hydroxylase (Cyp1a2) enzyme activities, we developed stable transfectants of plasmids containing the murine Cyp1a1 (cytochrome P(1)450) and the human CYP1A2 (P(3)450) cDNAs. We show that the assay measuring metabolism of ethoxyfluorescein ethyl ester (EFEE) was invaluable in screening large numbers of individual cell lines for high Cyp1a1 enzyme activity. Nine different plasmid constructs containing various combinations of promoter and enhancer sequences were compared, including: the Drosophila heat shock promoter, the mouse mammary tumor virus long terminal repeat (MMTV LTR) carrying the glucocorticoid-responsive element (GRE), enhancer sequences from simian virus 40 (SV40) and herpes simplex virus type 1 (HSV-1), and the aromatic hydrocarbon-responsive domain (AhRD) of the murine Cyp1a1 gene. Interestingly, only those constructs containing the AhRD produced high levels of Cyp1a1 enzyme activity. In contrast, high levels of CYP1A2 activity were obtained with plasmids carrying the HSV-1 enhancer, as well as the AhRD. These studies suggest that the AhRD, which responds to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), provides a post-transcriptional signal necessary for the induction of functional Cyp1a1 enzyme activity. Although untransfected c37 cells exhibit markedly elevated levels of endogenous Cyp1a1 mRNA, the expression of exogenous Cyp1a1 or CYP1A2 enzyme activity in these cells decreases the concentration of this endogenous Cyp1a1 mRNA to negligible levels and restores Cyp1a1 mRNA inducibility by TCDD; these data indicate that the functional product of either the Cyp1a1 gene or the CYP1A2 gene might have a role in an autoregulatory loop controlling the constitutive expression of the Cyp1a1 gene. The cell lines described herein should be valuable in assessing the contribution of these two P450 enzymes to the processes of cytotoxicity, mutagenesis, and carcinogenesis. PMID- 2206400 TI - Characterization by cDNA cloning of the mRNA for seminalplasmin, the major basic protein of bull semen. AB - A cDNA library derived from poly(A)+RNA of bull seminal vesicle tissue was screened with synthetic DNA probes specific for seminalplasmin (SAP), the major basic protein of bull semen. From a number of positive clones, pBSV12, containing a 577-bp insert, was identified and sequenced. The derived amino acid sequence comprises the known amino acid sequence of SAP with an amino terminal representing a putative signal sequence; at the carboxyl terminus the sequence contains an additional lysine residue. Present experimental data do not distinguish between two potential SAP precursor molecules, each starting with a methionine residue and differing by 10 amino acid residues in the leader peptide. Comparative Northern analysis reveals a SAP-specific mRNA of 700 bp, which lacks RNA from bovine testis as well as from seminal vesicle tissue of a bull calf; hence, expression of the SAP gene appears to be under androgen and/or developmental control. Southern analysis indicates that one gene appears to specify SAP. SAP-like DNA sequences were detected in ovine and porcine genomic DNA. PMID- 2206401 TI - Specific cytosine demethylations within the first exons of the rat CYP2D3 and CYP2D5 genes are associated with activation of hepatic gene expression during development. AB - To investigate the mechanism of transcriptional activation of the CYP2D gene subfamily in rat liver during development, Northern blot analysis and DNA methylation tests using Hpa II and Hha I enzymes, which are sensitive to cytosine methylated DNA, were carried out. As the result of mRNA measurements, these genes were classified into two patterns of expression, (i) late-onset gene activation in which mRNA gradually increases until rats reach puberty and (ii) early-onset expression in which the peak of mRNA expression is reached within 1 week after birth. The CYP2D3 and CYP2D5 genes, representatives of late-onset and early-onset expression, respectively, were examined. A correlation was found between mRNA expression during development and demethylation of cytosine residues located at the same position in the first exons of both the CYP2D3 and CYP2D5 genes. These results suggest that specific demethylation events are associated with developmentally programmed hepatic gene activation. PMID- 2206402 TI - Rapid detection of hypervariable regions by the polymerase chain reaction technique. AB - The polymerase chain reaction (PCR) technique has provided a substantial improvement for the detection and analysis of known genetic polymorphisms. Here, we describe the application of this method for the detection of variable number of tandem repeat (VNTR) sequences. With the use of unique oligonucleotide primers, flanking the repeat sequence, and the thermostable Taq DNA polymerase, the hypervariable regions 3' of the Ha-ras gene, 3' of the apolipoprotein B gene, and 5' to the joining segments of the heavy-chain immunoglobulin gene could be amplified. Alleles up to 2,000 bp could be visualized directly on ethidium bromide-stained agarose gels. Larger alleles were seen only after traditional Southern blot analysis with an internal probe. The value of this new approach for the detection of VNTRs is illustrated in a case of paternity dispute. PMID- 2206403 TI - [Minor malformation score in congenital cleft of the lip and palate]. AB - The authors analyzed minor malformation score in 63 children (36 boys and 27 girls) with congenital cleft of the lip and palate in order to evaluate purposefulness of its application as a screening method in detecting various major malformations. The results obtained revealed extremely increased minor malformation score in our patients and confirmed that an increased minor malformation score is associated with major malformation, i.e. clefts of the lip and palate. Therefore, it could be used as a screening method for detection of major malformations. PMID- 2206404 TI - [A cephalometric analysis of cases with open bite]. AB - A cephalometric study of 46 cases of both sexes, with open bite (experimental group), aged 10 to 18 years, was performed. The control group consisted of 180 cases with normal occlusion. A total, of 38 linear and angular variables were analyzed. Age variable as well as sex-related differences were also estimated. Compared with the control group, experimental group demonstrated significantly higher mean values for the following variables: lower segment of the mandibular angle, mandibular angle, basal angle, Bjork's polygon, mandibular anterior cranial base planes angle and Y-axis angle. The proportion between the facial hights was significantly decreased in the experimental group. In addition, retroclination of the lower incisors was significantly higher in the experimental than in the control group. Only four linear variables showed significant sex differences. It may be concluded that there are no significant sex difference for most of morphological characteristics of the viscerocranium. PMID- 2206405 TI - [Skeletal variations in children with Class II division 1 malocclusion]. AB - The aim of this investigation was to determine skeletal variations in patients with class II division 1. malocclusion. It was analyzed sagittal position of upper and lower jaws in relation to the cranial base. The sample consisted of 45 patients of both sexes, aged between 7 and 14 years. Antero-posterior position of maxilla and mandible in relation to the cranial base was assessed from tracings of lateral cephalometric radiographs of angles SNA and SNB and inter-jaw relationship from tracings of angle ANB by the Steiner's method. The angles of maxillary and mandibular inclination were measured by the Schwarz's method. Mean values were determined, as well as skeletal variations and their distribution together with combination of maxillary and mandibular inclination and their percentage of occurrence in our sample. Five different variations of skeletal type were identified: combination of maxillary and mandibular retrognatism was predominant (68.89% of cases); maxillary prognatism combined with mandibular retrognatism followed with 13.33% of cases; combined prognatism of both jaws was found in 6.67% of cases, and so was orthognathism of upper jaw with retrognathism of mandible, while maxillary prognathism with mandibular orthognathism was recorded in 4.44% of cases. The analysis of jaw inclination shows the greatest percentage of maxillary anteinclination and mandibular retroinclination (46.67%); 33.33% of children had retroinclination of both jaws; 13.33% of cases had normoinclination of maxilla and retroinclination of mandible; in 3 cases other rare combinations were found. Results indicate the necessity for differential approach to orthodontic treatment of this anomality. PMID- 2206406 TI - [Systematic care of oral cavity in school children during two-year period]. AB - A detailed care program of dental caries in children of primary schools for the period of two years is described. This program is multilateral and represents the average value with a possibility to move to the minimum or maximum of health service intending to retain continuity of its realization. This program engages more medical professions and represents an integral part of multilateral medical measures with the purpose of realizing health policy and its main scope, i.e. health prosperity. Such preventive program is economical, by avoiding later expensive treatment, and improves national health including reduction of malocclusions. Realization of this preventive program represents the imperative of contemporary health policy in stabilization of the society as well as more national behaviour in carrying out the health policy. PMID- 2206407 TI - [Rotation of canines and its treatment with fixed appliances]. AB - After an introductory consideration of rotation of the canines, results of orthodontic treatment of 4 cases with rotated canines are shown. All cases were treated by fixed appliances. To prevent relapse, section of supraalveolar fibers was made in all cases treated. PMID- 2206408 TI - [Dimensions of deciduous and permanent incisors in cases with Class II division 1 and 2 malocclusions]. AB - The analysis of mesiodistal dimensions of the upper and lower incisors (in total and separately) has been carried out in order to investigate the interdependence of sizes of the teeth with defined malocclusions. The investigation included 180 cases of both sexes, out of which 90 had deciduous dentition and other 90 examinees had permanent dentition. There were 120 examinees with Class II malocclusion (60 with Class II/1, and 60 with Class II/2), whereas the rest of 60 examinees with normal occlusion were used as the control group. Gnathometric measurements were made on the plaster casts with calipher precision of 0.1 mm and were double checked. Computer analysis of the results obtained emphasized the following: the heterogeneity of findings in the deciduous dentition does not allow hypothesis of a connection between sizes of the deciduous incisors and defined malocclusions; in the permanent dentition the examinees with Class II division 1 malocclusion have significantly the largest incisors, and the smallest the examinees with class II division 2 malocclusion; the greatest difference in the size between the deciduous and permanent incisors was found in the examinees with Class II division 1 malocclusion and the smallest difference was found in the examinees with normal occlusion. PMID- 2206409 TI - [Measles: control, elimination or eradication?]. PMID- 2206410 TI - [Vaccination against measles. The situation in Mexico and America. Advances in the method of aerosol immunization]. AB - We present general comments on the epidemiology of measles considering the pre vaccine era as well as the post-vaccine period in which some changes can be observed: the decrease in morbidity and mortality, the extension of the inter epidemic interval, the increase in the mean age of infection, etc. We make some estimations about the vaccine coverage and the ideal age of immunization for the goal of eradication (assuming a lifelong immunity for the vaccinees). The technical problems in measles immunization are also revised explaining why no continental country has been able to eliminate the disease. We describe the epidemiological situation in North America, Mexico and Latin American countries. Lastly we present the Mexican experience with the inhaled aerosolised vaccine: the studies in Monterrey (Sabin et al, 1982), other investigation in Mexico, D.F. and in the State of Jalisco, as well as the mass campaigns in Aguascalientes in 1988 and in Coahuila and Nuevo Leon in 1989. We propose it as an effective, harmless, simple, inexpensive and practical method. PMID- 2206411 TI - [Epidemiologic overview of measles in Mexico: current situation and perspectives]. AB - It has been recognized that due to immunization campaigns and specific treatment of medical complications, has resulted in a reduced measles mortality in Mexico as in others countries. However, during the last few years the number of measles cases in Mexico has shown an increasing trend over previous years due to two larges epidemics, in 1985 and 1989. As a vaccine preventable disease, the number of measles cases has shown an important decline in mortality as compared with mortality in the general population. From the total deaths in children under five years the measles deaths have been reduced from a level of 2.8% in 1969 to a level of 1.6% in 1985. The more recent mortality data available shows that 597 deaths caused by measles were registered in 1986, for a mortality rate of 0.75 per 100,000 inhabitants. At higher rate was observed in the age groups less than 1 year with a mortality rate of 5.9 per 100,000 inhabitants compared with 4.2 in the group from 1 to 4 years. The morbidity epidemiologic surveillance system among governmental health services reported a total of 20,076 cases in 1989, with an incidence rate of 23.8 cases per 100,000 inhabitants and a estimated mortality rate of 6.6%. This recent emergence of the measles activity in Mexico is part of a pandemic that is affecting several countries around the world. The impact of these cases on an increased demand of medical care as well as its clinical complications, outcome and mortality, makes measles a high priority problem in Mexico. PMID- 2206412 TI - [Immuno-epidemiologic considerations on the prevention of measles in Mexico]. AB - Study results of passive natural immunity anti-measles, and immune response to measles vaccine from different strains in Mexican children under one year old, are described in this paper. Mexican infants in these studies ended their maternal immunity at 8-10 months of age. Edmonston-Zagreb (EZ) vaccine strain had higher seroconversion rates comparing to Schwarz strain. Dose response effect was more closely related to Schwarz strain than EZ, since difference in seroconversion rates with standard, medium and high doses were statistically significant. However geometric mean post-vaccination titers were higher in children vaccinated with Schwarz strain, than EZ receptors. PMID- 2206413 TI - [Epidemiologic investigation of measles in Mexico. A methodological proposal]. AB - The epidemiological study of measles needs a critical perspective in addition to a descriptive study of variables in time, place and person. The goal of this critical and methodological study of measles is to evaluate the coverage and efficacy of the vaccine in the affected population. These indicators will provide an indirect evaluation of the preventable services. This document presents a general view of the epidemiological design of cohorts and case-control studies and their immediately application to the study of measles. It describe the mathematical procedures for calculating the coverage and efficacy of the measles vaccine in community and hospital outbreaks. PMID- 2206415 TI - [Nosocomial measles: a proposal for its control in hospitals]. AB - The transmission of measles in medical settings has become increasingly recognized. Due to the lack of information on nosocomial measles in Mexico we performed a 14 year retrospective study at the Hospital Infantil de Mexico Federico Gomez. The objectives of our study were: a) to determine the frequency of the disease in our hospital; b) to determine the association between nutritional status and risk of acquiring nosocomial measles and c) to establish the relationship between nutritional status and complications in morbidity and mortality due to nosocomial measles. Eighty nine children with nosocomial measles were identified. We observed that patients with severe malnutrition had a greater risk of acquiring nosocomial measles developing complication and dying. The most frequent complication was pneumonia. PMID- 2206414 TI - [Measles outbreak in the indian community of Yaitepec, Oaxaca, 1988]. AB - A measles outbreak that involved 230 cases occurred in 1988 in Santiago Yaitepec, Oaxaca, had an attack rate of 14% and a case-fatality ratio of 3.9%. That community is relatively speaking isolated. A pre-outbreak measles vaccine coverage of 38.7% was found among children 1-15 years old. We compared attack rates among vaccines and non-vaccines and adjusted the figures for age and source of vaccine information. The vaccine efficacy based on this comparison was 72%. We classified cases as primary and secondary for household level. The secondary attack rate was 15.5%. The comparison based on secondary attack rates yield an estimate of vaccine efficacy about 95%. The implications of the epidemic recurrence of measles for attack rates yield an estimate of vaccine efficacy about 95%. The implications of the epidemic recurrence of measles for isolated communities due to suboptimal vaccine coverage are discussed. PMID- 2206416 TI - [The social impact of the vaccination against measles in Mexico. Comments during the course of the epidemics of 1988-1990]. AB - A number of issues have arisen concerning the current measles epidemic. In this paper we review: 1) the causes of this cyclic rise; 2) the benefit of a vaccination program sustained during more than 15 years; 3) the vaccine efficacy, as well as 4) the vaccination coverage goal for controlling measles. Immediate causes of the epidemic recurrence are: 1) low vaccination coverage, and 2) an increasing absolute number of newborns enlarges the pool of susceptibles. A strategy to identify now-vaccinated children in a systematic fashion is suggested. As long as measles transmission occurs even if measles vaccination coverage increases, the proportion of vaccinated cases will not decrease. Within optimal values of vaccine efficacy this proportion will increase as the coverage increases. The universal goal for measles vaccination is stressed. PMID- 2206417 TI - [Evaluation of the cold chain and follow-up of the potency of the antimeasles vaccine in the field]. AB - In order to evaluate the quality of the measles vaccine, it was carried out a study in three states of Mexico (Durango, San Luis Potosi and Yucatan) during the intensive vaccination campaign in 1986. Edmonston-Zagreb measles vaccine vials were obtained from the different administrative-sanitary levels of the Ministry of Health in Mexico. Interviews were performed to the vaccine responsibles. Questionnaires had the following aspects of the cold chain: storage, preservation, control and transport of measles vaccine. Answers were evaluated through a system, where 100% indicated the necessary and sufficient level to get a good operating of the cold chain. The vaccine potency did not have variations under the minimum titre recommended for the World Health Organization (W.H.O.). The three states had the following compliment of the cold chain norms: 1) Central state level: 83% in storage, 80% in preservation, 100% in control and 100% in transport norms; 2) Regional level (jurisdiction): 87% in storage, 51% in preservation, 93% in control and 100% in transport norms; 3) Local level: 83% in storage, 64% in preservation, 83% in control and 33% in transport norms. PMID- 2206418 TI - [Titration and stability tests for antimeasles vaccine]. AB - Production and quality of the vaccines, are important activities in the prevention of measles disease. Edmonston-Zagreb measles vaccine is the main strain attenuated virus distributed in Mexico. In order to evaluate the titer of Edmonston-Zagreb and Schwarz vaccines, 50% tissue culture infective dose (TCID50/0.5 mL) and plaque-forming units (PFU) are performed in the National Laboratory of Public Health. Furthermore PFU is a method used in the stability vaccine test. Validation criteria are described in this paper. PMID- 2206419 TI - [Direct and indirect effects of vaccines: an annotation on the estimation of the vaccine efficacy from outbreaks caused by acute infection agents such as measles]. AB - A good measure of the efficacy of vaccines should be based on an index that standardizes the exposure to infection of those who have been immunized and those who have not. In addition, the measure should not be influenced by indirect effects. In the case of outbreaks directly transmitted agents that cause acute infections diseases, the household secondary rates of attack are the best indicator of vaccine efficacy provided that the data are collected at the household level. If the data are not collected in this manner, the best indicator will be the estimated probability of transmission, even though this estimator and its meaning less obvious than the secondary attack of rate. Other strategies to estimate the efficacy of an immunization are more appropriate for situations that are more complex than outbreaks caused by acute infectious agents. PMID- 2206420 TI - [Complications in children with measles]. AB - Ongoing immunization campaigns have significantly reduced the incidence of measles. To evaluate the efficacy of vaccination policies, however, it is necessary to analyze disease indicators of mortality and of morbidity such as medical complications and sequelae. We reviewed the hospital experience at Hospital Infantil de Mexico regarding children with measles who necessitated hospitalization between January 1976 and December 1989. During this 14 year period, 176 patients with measles were hospitalized; the majority of the cases corresponded to the period between 1985 and 1989. Fifty five percent of the cases corresponded to children under one year of age. Of those older than 12 months, 81% lacked an immunization history. Eighty percent were from Mexico city or from the neighboring state of Mexico. The mayor complications included: respiratory tract infections such as pneumonia (50.8%), diarrhea (18.2%), and less frequent: laringotracheitis, otitis media, myocarditis and pyodermitis. More than 70% were significantly (grade II or III) malnourished. Twenty three patients died, for a mortality of 13%. The factors more likely related to measles mortality were; age less than two years, undernutrition, and more than two medical complications associated. This report emphasizes that medical complications and mortality are more likely to occur in very young unimmunized, malnourished children. PMID- 2206421 TI - [Pneumonia caused by measles: description of a clinical case of giant cell pneumonia in a non-immunosuppressed adolescent patient]. AB - Measles pneumonia is the most frequent complications associated with mortality in this infection. There are two types, one corresponds to the giant-cells pneumonia and the other one to lung superinfection after measles infection. The first one has been occurred in immunosuppressed patients, without rash. We reported a measles pneumonia case in a previously healthy adolescent girl who had a fatal pneumonia by giant cells demonstrated by open lung biopsy. The review of the literature showed that this is very unusual in normal population. PMID- 2206422 TI - [Guidelines for vaccination against measles in children]. AB - After the introduction of massive immunization campaigns in Mexico, started in 1973, the measles mortality rate has been reduced in children under five years of age from 2.8% in 1989 to a level of 1.6% in 1985. Two epidemics occurred in 1985 and 1989 with 19,460 and 20,076 reported cases respectively. In the first quarter of 1990 a total of 22,906 cases were reported. The age distribution has been: patients greater than 1 year 26.3%; 1-4 years 24.8%; 5-14 years 35.5% and greater than 15 years 18.2%. The vaccination coverage, between 1987 and 1988, ranges from 34% to 75% in outbreaks studies and in the National Health Survey. The vaccine efficacy in those outbreaks has been estimated from 63% to 89%. The epidemics have been primary related to low vaccination coverage during the last 15 years. The conglomeration of a cumulative number of non vaccinated persons could explain the distribution of cases in all age groups. The strategy based on two doses as has been recommended in the US, is useful in programs addressed to eradicate measles, but the low resources and limited access to health services in rural communities of Mexico have made these control measures in feasible. The measles control in Mexico, must be based in vaccinate each child at the first anniversary, this strategy could be enough to take off the measles epidemics. PMID- 2206423 TI - Activity and distribution of learning-related neurons in monkey (Macaca fuscata) prefrontal cortex. AB - The involvement of monkey (Macaca fuscata) prefrontal cortex (PFC) neurons in motor output decisions was studied by recording single neuron activity during 3 tasks: (a) go-left, go-right, or no-go decisions, (b) operant bar press feeding based on discrimination of food and nonfood, and (c) either delayed matching-to sample (DMS) or DMS with response delay. Combinations of single neuron responses during the 3 tasks suggested 7 types of PFC neurons that were related to attention, choice, task-unique memory, reward anticipation, laterality, initiation of movement, and suppression of movement. The authors suggest that responses of PFC neurons do not depend on physical properties of the stimuli, but on their behavioral significance. PFC neurons might be important for appropriate behavior in response to external stimuli and internal or motivational factors. PMID- 2206425 TI - Hippocampal and prefrontal cortex contributions to learning and memory: analysis of lesion and aging effects on maze learning in rats. AB - Young adult rats with bilateral lesions to the hippocampus or prefrontal cortex, young operated controls, and normal old rats were tested on two complex mazes in the Hebb-Williams series. Approximately half the animals were previously trained on one of the mazes; the remainder received no previous training. The trained hippocampal rats showed sparing of memory for the general skill of maze learning but poor recall of the specific maze on which they had been previously trained. The opposite pattern was observed in trained prefrontal rats. In contrast, the aged rats' memory for maze-specific and maze-general information was impaired. The results confirmed the importance of the hippocampus for recalling highly specific information and pointed to a possible role for the frontal lobes in learning and remembering nonspecific skill-related information. The generalized deficit of the aged rats indicates that both types of memory were compromised and offers further evidence of frontal lobe and hippocampal dysfunction in normal aging. PMID- 2206424 TI - Amygdaloid complex lesions differentially affect retention of tasks using appetitive and aversive reinforcement. AB - The hypothesis that the amygdaloid complex (AC) is involved in the formation of stimulus-reward associations was examined. A series of experiments (1A-1C) directly compared the effects of lesions (produced by injection of the excitotoxin N-methyl-D-aspartic acid) on 1-trial appetitive and 1-trial aversive learning in rats. Experiments 1A and 1B, which used different degrees of reinforcement, revealed no effect of lesions on the appetitive task, whereas acquisition of the aversive task was significantly impaired. This impairment depended on the nature of the aversive reinforcement used: Impairment was seen when a highly aversive stimulus (footshock) was used but not when a less aversive stimulus (0.2% quinine solution) was used. Control experiments indicated that the effect of lesions was not due to reduced sensitivity to the foot-shock. In Experiment 2, a novel odor conditioning task examined further the effect of AC lesions on the acquisition of appetitive and aversive stimulus-reinforcement associations. As in Experiment 1, the AC lesions impaired learning of the aversive association but did not significantly influence the appetitive association. It is argued that, although the AC may be involved in some types of appetitively rewarded learning, the findings of a differential effect of AC lesions on aversively rewarded learning suggest a role in learning beyond the formation of stimulus-reinforcement associations. PMID- 2206426 TI - Cognitive and motor deficits in the performance of an object retrieval task with a barrier-detour in monkeys (Cercopithecus aethiops sabaeus) treated with MPTP: long-term performance and effect of transparency of the barrier. AB - To assess the stability of neural deficits produced by 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), the performance of monkeys on an object retrieval (detour) task was studied. The task required retrieval of a banana slice from a transparent box open on one side and fastened to a tray in front of the cage. The orientation of the open side, position on the tray, and position of the banana in the box were manipulated to vary the difficulty of the trials. Six African green monkeys (Cercopithecus aethiops sabaeus) were treated with MPTP (1.5-1.6 mg/kg cumulative doses over 4-5 days) and compared with 5 saline-treated control monkeys. The MPTP-treated monkeys had no gross neurological deficits but did have motor and cognitive deficits during acquisition of the object retrieval task 8-12 months after treatment (J. R. Taylor, Elsworth, Roth, Sladek, & Redmond, in press). Performance on the task was examined for 3 months after it had been learned. The MPTP-treated subjects reached at the barrier (transparent side) significantly more than controls and were less successful at retrieving the reward on the 1st reach than controls. Although they took longer to initiate the reach and had more motor problems than controls, they were as likely as controls to retrieve the reward in the end. These deficits remained stable throughout testing. An opaque but otherwise identical box was used randomly on some trials. MPTP-treated subjects decreased barrier reaches to control levels on trials in which the opaque box was used, whereas motor problems increased compared with trials in which the transparent box was used. The task can detect subtle performance deficits similar to those found in Parkinson's disease. PMID- 2206427 TI - Processing of form stimuli presented unilaterally in humans, chimpanzees (Pan troglodytes), and monkeys (Macaca mulatta). AB - Visual forms were unilaterally presented using a video-task paradigm to 10 humans, 3 chimpanzees, and 2 rhesus monkeys to determine whether hemispheric advantages existed in the processing of these stimuli. Both accuracy and reaction time served as dependent measures. For the chimpanzees, a significant right hemisphere advantage was found within the first 3 test sessions. The humans and monkeys failed to show a hemispheric advantage as determined by accuracy scores. Analysis of reaction time data revealed a significant left hemisphere advantage for the monkeys. A Visual Half-Field x Block interaction was found for the chimpanzees, with a significant left visual field advantage in Block 2, whereas a right visual field advantage was found in Block 4. In the human subjects, a left visual field advantage was found in Block 3 when they used their right hands to respond. The results are discussed in relation to recent reports of hemispheric advantages for nonhuman primates. PMID- 2206428 TI - Chemosensory conditioning of Hermissenda crassicornis. AB - Bite-strike responses of Hermissenda crassicornis, elicited by chemosensory stimulation of the lips, were found to be modified when food extracts were paired with rotation-produced stimulation of the statocysts. Animals that received repeated pairings of an extract of 1 food (conditioned stimulus, CS) with rotation exhibited suppressed bite-strike responses to that food for up to 48 hr after training. This suppression was usually specific to the trained food and was pairing-specific as well. Discriminative conditioning was also demonstrated. Animals trained with 1 CS paired with rotation and a second CS that was unpaired (CS-) showed suppressed bite-strike responses to the first CS. The results demonstrate that Hermissenda can learn to avoid foods that reliably signal an aversive event and may allow an analysis of higher order conditioning phenomena. PMID- 2206429 TI - Acquisition of conditioned associations in Hermissenda: additive effects of contiguity and the forward interstimulus interval. AB - Conditioned suppression of photokinesis by the marine mollusc Hermissenda was examined in 3 experiments. In each experiment, groups of animals received light (the conditioned stimulus, CS) that was paired with high-speed orbital rotation (the unconditioned stimulus, UCS), light and rotation explicitly unpaired, or no exposure to these stimuli. Twenty-four hours after training, all animals were tested for suppression of photokinesis in the presence of the light. To establish the effectiveness of our conditioning procedure, in Experiment 1 individual groups of animals received either 50, 100, or 150 CS-UCS pairings. Fifty pairings resulted in a marginal suppression of photokinesis, whereas 100 and 150 pairings produced strong suppression. In Experiment 2, the delay between CS onset and UCS onset was varied between 1 and 10 s. The 10-s interstimulus interval (ISI) did not support conditioning, whereas 1-s and 2-s ISIs were effective. As predicted by the current understanding of Hermissenda's neural network, in Experiment 3 it was found that CS-UCS pairings in which the CS preceded the onset of the UCS and terminated with the offset of the UCS evoked stronger conditioned suppression than either a CS that preceded the UCS and terminated with its onset or a CS that was paired in simultaneous compound with the UCS. This result indicates that CS UCS contiguity as well as the forward ISI act additively to establish the CS-UCS association. In none of the 3 experiments were any differences observed between groups that were untreated and that received the CS and UCS unpaired. In total, these experiments suggest strong similarities in the temporal characteristics of associative learning in Hermissenda and vertebrate species. PMID- 2206430 TI - Central dopamine turnover in guinea pig pups during separation from their mothers in a novel environment. AB - Guinea pig pups that were separated from their mothers and placed into a novel environment for 90 min showed an increase in dopamine (DA) turnover (ratio of metabolites to DA) in the septum compared with undisturbed baseline controls. Pups placed into the novel environment with their mothers exhibited an intermediate level of DA turnover. After 24 hr of separation in the novel environment, pups' DA turnover in the septum had returned to the baseline level. DA turnover in the caudate nucleus was unaffected by these procedures. Also, turnover in both septum and caudate nucleus when pups were not separated was positively correlated with the number of vocalizations emitted during 30 min of separation. These results closely parallel findings in separated monkeys and indicate that the guinea pig represents a useful rodent model for studying such effects. That elevated DA turnover during separation occurred in the septum suggests involvement of the mesolimbic system. PMID- 2206431 TI - An animal model for the behavioral effects of interferon. AB - Interferon, which is produced during viral infections, has cognitive and neurological effects in humans. A dose of 1600 U/g of mouse interferon-alpha significantly depressed horizontal activity, head pokes into a food chamber, and food intake in mice 10 hr and 24 hr after injection. An 800 U/g dose had only slight effects on horizontal activity and food intake, whereas a 400 U/g dose had no effect. There was no evidence of sensitization to interferon when a second 400 U/g dose was given after the 1600 U/g dose. The results imply that mouse interferon-alpha can be used in mice as a model for studying the fatigue and anorexia produced by interferon. PMID- 2206432 TI - Strain-dependent morphine-induced analgesic and hyperalgesic effects on thermal nociception in domestic fowl (Gallus gallus). AB - The effects of morphine (30 mg/kg), naloxone (5 mg/kg), and morphine with naloxone on distress vocalizations and thermal nociception were examined in different strains of domestic fowl. Naloxone by itself did not significantly affect vocalizations or thermal nociception. Morphine produced a naloxone reversible attenuation of vocalizations that was not strain dependent. Morphine produced a strain-dependent analgesic (Rhode Island Red strain) and hyperalgesic (White Leghorn and Cal-White strains) effect on tests of thermal nociception. Both the analgesic and hyperalgesic effects were reversed by naloxone. These opposite effects on thermal nociception may reflect the effects of selective breeding on opioid receptor subtype. PMID- 2206433 TI - Subfornical organ participates in salt appetite. AB - The effects of subfornical organ (SFO) lesions on salt and water intakes after sodium depletion were studied. Water and salt intakes were measured over 45 hr during a regimen that combined furosemide diuresis and access to low-sodium diet. Water was solely available for 23 hr after diuresis, and water and 0.3 M NaCl solution were available in choice for the next 22 hr. After diuresis, rats with SFO lesions drank significantly less water in 2 hr than controls but achieved equivalent water and sodium balances before salt access 20 hr later. After salt access, rats with SFO lesions drank significantly less saline and water in 2 hr than controls but had similar saline and water intakes over the next 20 hr. Thus, SFO lesions blunted acutely, but not chronically, saline and water intakes to sodium depletion, and the blunted intakes are not explainable by hydrational status. PMID- 2206434 TI - Preoptic angiotensin and salt appetite. AB - Two experiments were designed to test whether angiotensin (ANG) synthesis or receptor activation in the ventral preoptic region is critical for ANG-induced salt appetite in rats. In Experiment 1, infusions of ANG into the subfornical organ (SFO) produced water drinking without saline intake, but infusions near the organum vasculosum laminae terminalis (OVLT) produced both water and saline drinking. Thus, forebrain areas that support water drinking to ANG do not all support salt appetite. In Experiment 2, rats were given oral captopril (CAP) to enhance daily intake of water and saline solution by increasing ANG II synthesis in the brain. CAP microinjected into the SFO reduced CAP-enhanced water drinking without affecting saline intake, but CAP in the OVLT reduced enhanced saline intake without affecting water drinking. Thus, ANG acting in the OVLT, the most ventral part of the median preoptic nucleus, or other nearby structures is important for ANG-induced salt appetite. PMID- 2206436 TI - [Possible interference with the "pill" by antibiotic therapy]. PMID- 2206435 TI - [Therapy of a maxillary second molar with 5 root canals]. PMID- 2206437 TI - [Flap design in extraction of impacted third molars]. PMID- 2206439 TI - [Unimetric screw]. PMID- 2206438 TI - [Unusual case of bilateral giant cell epulis]. PMID- 2206440 TI - [Adaptation of an adhesive resin to etched metals]. PMID- 2206441 TI - [Silane coupling agents]. PMID- 2206443 TI - [Corrosion and biocompatibility of dental alloys]. PMID- 2206442 TI - [Canal treatment with Vebas cement]. PMID- 2206444 TI - [Preparation of the intrasulcular portion of prosthetic stump in relation to the marginal periodontium]. PMID- 2206445 TI - [Marginal accuracy of veneers fabricated in porcelain]. PMID- 2206446 TI - [Removal of root canal prefabricated posts for orthograde endodontic retreatment]. PMID- 2206447 TI - [Pre-extraction prostheses: purpose-function-materials]. PMID- 2206448 TI - [Comparison of the adhesive force of a composite cement and a resin cement]. PMID- 2206450 TI - [Clinical crown lengthening]. PMID- 2206449 TI - [Rare case of follicular cyst]. PMID- 2206452 TI - [The Dentatus screw]. PMID- 2206451 TI - [Stereomicroscopic evaluation of 3 root canal obturation technics]. PMID- 2206454 TI - Partial purification and properties of cathepsin G-like proteinase of mouse myeloid leukemia M1 cells. AB - A proteinase extracted with 1M NaCl from particulate fraction of the postnuclear fraction of mouse myeloid leukemia M1 cells was partially purified by Bio-Gel HTP treatment and Sephadex G-75 gel filtration. The apparent molecular mass of the proteinase was 26,000 Da and the isoelectric point was about pH 10. The enzyme activity was inhibited by phenylmethanesulfonylfluoride, chymostatin, and soy bean trypsin inhibitor. It hydrolysed specifically Suc-Ala2-Pro-Phe-4 methylcoumaryl-4-amide (MCA). NaCl and KCl enhanced several times the activity for Suc-Ala2-Pro-Phe-MCA, but not that for fluorescein-labeled albumin and fibrinogen. These enzymic properties of the major proteinase are similar to those of chymotrypsin and cathepsin G. The role of a cathepsin G-like proteinase in relation to M1 cell differentiation is discussed. PMID- 2206453 TI - Structure and function of L-lactate dehydrogenases from thermophilic and mesophilic bacteria, X. Analysis of structural elements responsible for the differences in thermostability and activation by fructose 1,6-bisphosphate in the lactate dehydrogenases from B. stearothermophilus and B. caldolyticus by protein engineering. AB - The amino-acid sequences of the lactate dehydrogenases (LDH) from B. stearothermophilus and B. caldolyticus differ at only 10 positions. The properties of these enzymes however show substantial differences. The LDH from B. stearothermophilus is activated by Fru-P2 and has a higher thermostability (10 degrees C) than the enzyme from B. caldolyticus which cannot be activated by Fru P2. To correlate these functional differences to the structural properties, we have constructed a set of hybrid- and point-mutants of the two LDHs. The amino acids at positions 207, 209B, and 209C could be identified to confer the property of activation by Fru-P2 to the enzymes. This part of the enzyme is to a large extent also responsible for the different thermostabilities of these two proteins. PMID- 2206455 TI - Cooperativity and intermediate states in the T----R-structural transformation of insulin. AB - With respect to T----R-structural transformation, cobalt insulin hexamers appear as dimers of two positively cooperative trimers which are related by negative cooperativity. Transformation of the first trimer causes polarization of the hexamer which is insurmountable by inorganic anions (SCN theta) used as transforming agents, and in the case of phenolic agents (m-cresol), which can achieve complete transformation of the hexamer, allows the identification of the T3R3 intermediate. Zinc insulin hexamers are also transformed in a stepwise manner, but for the first step the sigmoidal shape of the titration curve cannot be detected. PMID- 2206456 TI - A facile method for the isolation and preparation of proteins and peptides for sequence analysis in the picomolar range. AB - We report a new and facile extraction method of proteins and polypeptides in the range of 100 to 1 kDa previously separated by high-resolution SDS/polyacrylamide gel electrophoresis. Proteins and polypeptides obtained by chemical or proteolytic cleavage of proteins can directly be applied to high-sensitivity N terminal amino-acid sequence analysis by gas-phase sequencing. The Coomassie Blue stained protein bands are eluted from the gel slices with 0.1 M sodium acetate buffer, pH 8.5, 0.1% SDS in high yield and directly applied to the filter disc of the gas-phase sequencer. The superior efficiency for the isolation of proteins and polypeptides from polyacrylamide gels for microsequencing has been documented by a quantitative comparison of the procedure described here and the favoured electroblot-transfer method using 14C-labeled marker proteins. This highly efficient isolation has been successfully reproduced and applied to the analysis of a variety of proteins and peptides with rather divergent physical properties, particularly to hydrophobic peptides isolated from SDS/polyacrylamide gels. The electrophoretic transfer onto activated glass filters. Immobilon membranes (polyvinylidene-difluoride membranes), siliconized or chemically activated glass fiber supports can be omitted. The method considerably simplifies and speeds up the isolation, and improves the sensitivity as compared to the electroblotting procedures due to the reproducibly high recoveries. PMID- 2206457 TI - Effect of nonenzymatic glycation on the structure of immunoglobulin G. AB - Incubation of human immunoglobulin G with glucose in vitro leads to covalent incorporation of the sugar concomitant with marked changes in molecular structure. After six to ten days of glucose incubation, absorption at 350 nm and fluorescence at 440 nm upon excitation at 370 nm markedly increased, indicating formation of nonenzymatic browning products. Furthermore, immunoglobulin G derivatives of a molecular mass of 500,000 Da appeared during glucose incubation as revealed by gel filtration. Electrophoretic examination of the 500-kDa protein revealed the formation of covalently bound immunoglobulin G polymers. Compared with nonglycated monomeric immunoglobulin G, functional properties of the 500-kDa protein, such as binding of protein A and fixation of complement are markedly reduced. PMID- 2206458 TI - On the action of carboxy groups in the citrate synthase reaction. AB - The aza analogue (RS)-3-hydroxy-2,5-pyrrolidinedione-3-acetic acid (6) of the five-membered citric anhydride (2) was prepared in the sequence citric acid----2 phenyl-1,3-dioxolan-4-one-5,5-diacetic acid (1)----citric acid beta-amide (3)--- 6 and used to resolve ambiguities in the mechanism of the citrate synthase reaction. The results yield no indication for the formation of anhydride 2 on the enzyme and favour the direct hydrolysis of the intermediate (3S)-citryl-CoA. Ammonolysis of the dioxolanone 1 in the reaction sequence described above produced not only citric acid beta-amide but also the alpha-isomer. This is shown to originate in the transient formation of anhydride 2. Hydrolysis of the dioxolanone 1 under "physiological conditions" occurs via anhydride 2, generated in intramolecular bifunctional catalysis by a protonated and a deprotonated carboxyl group. The catalytic residue Asp375 of citrate synthase is considered to operate on the enzyme as does the protonated carboxyl group in the chemical reaction and to generate enolic acetyl-CoA in cooperative catalysis with His274. This reaction of Asp375 may also facilitate the hydrolysis of citryl-CoA. PMID- 2206459 TI - 4-Methylumbelliferyl-alpha-glycosides of partially O-acetylated N acetylneuraminic acids as substrates of bacterial and viral sialidases. AB - 4-O-Acetylated, 7-O-acetylated, and 9-O-acetylated 4-methylumbelliferyl-alpha-N acetyl-neuraminic acids (Neu4,5Ac2-MU, Neu5,7Ac2-MU, Neu5,9Ac2-MU) were tested as substrates of sialidases of Vibrio cholerae and of Clostridium perfringens. Both sialidases were unable to hydrolyse Neu4,5Ac2-MU. This compound at 1 mM concentration did not inhibit significantly the cleavage of Neu5Ac-MU, the best substrate tested. The 4-O-acetylated sialic acid glycoside is hydrolysed slowly by the sialidase from fowl plague virus. The relative substrate specificity, reflected in V/Km of the Vibrio cholerae sialidase is Neu5Ac-MU much greater than Neu5,7Ac2-MU approximately Neu5,9Ac2-MU and of the clostridial enzyme it is Neu5Ac-MU greater than Neu5,9Ac2-MU greater than Neu5,7Ac2-MU. The affinities of both enzymes for the side-chain O-acetylated sialic acid derivatives are higher than for Neu5Ac-MU. The artificial, well-defined substrates, described here, provide the opportunity to quantify the influence of sialic acid O-acetylation on the hydrolysis of sialoglycoconjugates without the side effects introduced by other parts of more complex glycans. PMID- 2206460 TI - Activation of the human leukocyte proteinases elastase and cathepsin G by various surfactants. AB - A systematic study comprising 28 synthetic ionic and nonionic surfactants was carried out in order to examine their effect on the activity of elastase and cathepsin G from human leukocytes against 4-nitroanilide substrates. The whole spectrum, ranging from a complete loss to a pronounced rise in enzymatic activity, was observed at a 0.1% (w/v) surfactant concentration. Most significantly, benzalkonium chloride led to a five-fold increase in elastase activity. PMID- 2206461 TI - A national study on biopsy-confirmed thyroid diseases among Koreans: an analysis of 7758 cases. AB - In order to determine the incidence and to understand recent trend of thyroid neoplasm and other thyroid diseases among Korean, a nation-wide collection of biopsy-confirmed and surgically removed thyroid lesions from 30 pathology laboratories of university and general hospitals was made over a 3-year-period from 1986 to 1988. These tumors and tumor-like lesions of the thyroid were classified according to the WHO classification. Results of this study were compared with those of the previous in Korea and other countries. Among the 7758 collected cases from 7449 patients, adenomatous goiter was the most common, comprising 2681 cases (34.6%), followed by follicular adenoma, 1868 cases (24.1%) and papillary carcinoma, 1474 cases (19%). Neoplastic condition comprised 48.8% (3786 cases). Of malignant tumors, papillary carcinoma was the most frequent accounting for 79.8%. The female to male ratio was 7.5:1 with female predominance. This female predominance was noted in all but two thyroid diseases. Medullary carcinoma showed equal distribution in both sexes, and two cases of malignant lymphoma developed in males. Thyroid diseases were common at the 3rd to 6th decades with peak incidence at the 4th decade. The right lobe of the thyroid was more frequently involved than the left lobe (1.6:1). The diagnoses were made largely on the surgically excised specimen (85.3%). Multiplicity of the lesions revealed single lesion in 64%, multiple and diffuse lesion in 36% of cases investigated. Average size of the lesion was in the range of 1-5 cm in diameter (62%). PMID- 2206462 TI - The enhancing effect of ethanol on the development of glutatione S-transferase placental form-positive foci induced by diethylnitrosamine in F344 rat. AB - The effects of ethyl alcohol and pig serum administration on the development of preneoplastic hepatic enzyme-altered foci were examined in an in vivo mid-term assay system. Rats were initially given a single dose (200 mg/Kg) intraperitoneal injection of diethylnitrosamine (DEN). Two weeks later, treatment was started with 10% ethanol + 10% sucrose solution, 10% sucrose solution, or tap water as drinking water for 6 weeks with or without intraperitoneal injection of porcine serum twice a week. All rats were subjected to a two-thirds partial hepatectomy at week 3. The modification potentials were evaluated by comparing the number and area per cm2 of glutathione S-transferase placental form-positive (GST-P+) foci in the liver of each group. As a result, ethanol significantly enhanced the development of GST-P+ foci. Unfortunately, the porcine serum injection produced no hepatic fibrosis and no significant alteration in GST-P+ foci. PMID- 2206464 TI - Antibody response of mouse splenocytes using mixture of supernatants of thymocytes, adherent and non-adherent splenocytes: in-vitro immunization-II. AB - We adapted one of the in-vitro immunization methods to induce antibody responses and confirmed the success of the immunization by enzyme-linked immunosorbent assay (ELISA) without hybridization. We have previously reported several methods of in-vitro immunization using different conditioned media. Here we introduce another method of in-vitro immunization using a mixture of three types of supernatant (thymocytes, and adherent and non-adherent splenocytes of mouse). Splenocytes were immunized in-vitro by a recombinant human growth hormone (rhGH) with the above conditioned media, and the results by ELISA showed a much higher optical density than the other in-vitro immunization methods that we had previously reported. Humoral responses as a result of in-vitro immunization to soluble antigens were easily confirmed by ELISA using the above-conditioned media. This finding indicates that any other conditions thought to be critical by other researches may not be essential for in-vitro immunization. PMID- 2206463 TI - Recurrent alternating stroke. AB - Recurrent alternating stroke, i.e., one time ischemic and the other hemorrhagic or vice versa, is an uncommon event. We report a series of eight patients who had recurrent alternating strokes, which were diagnosed by CT scans during the last four years. Infarcts preceded hemorrhage in six patients. In the remaining two patients, hemorrhage developed first and infarct followed. All ischemic strokes were the lacunar infarcts. The lesions of the two attacks were located in different sites in all cases except one. The mean age of the patients was 56.6 years at the time of the first attack and 57.5 years at the time of the second. The mean interval between attacks was 11.8 months. All patients were hypertensive on admission. After the first attack, the outcome was favorable in all patients. However, after the second attack the outcome deteriorated to moderate disability in three, severe disability in one and death in four. We discuss some possible reasons for the rarity of recurrent alternating stroke. PMID- 2206466 TI - Poorly differentiated carcinoma of the thyroid retrospective clinical and morphologic evaluation. AB - Five thyroid carcinomas showing clinically aggressive biologic behavior were retrospectively reviewed to evaluate the possible presence of morphologic differences from conventional thyroid carcinomas. They were originally diagnosed as follicular carcinomas, medullary carcinoma, papillary carcinoma, and mixed papillary and medullary carcinoma. There were three males and two females. The age at the time of initial diagnosis ranged from 36 years to 67 years (mean 56 years). The size of the tumor varied from 4.5cm to 10cm (mean diameter 7cm). One patient died of brain metastasis four years after the initial therapy and the other four patients are still alive with local recurrences and/or metastases to bone, spinal cord, lung, and buttock. Histologically these lesions are categorized into two different groups: insular variant and columnar cell variant. Insular variant was characterized by well-defined nests (insulae) that are composed of small, uniform cells, frequent tumor necrosis, and hyalinization of the stroma. Columnar cell variant was characterized by tall columnar cells with marked nuclear statification. All five cases stained positively for thyroglobulin and negatively for calcitonin. With the above clinical and histopathological findings, we interpreted these lesions as a poorly differentiated carcinoma, biologically in an intermediate position between well differentiated and anaplastic carcinomas. The rapid and often fatal outcome associated with these variants of poorly differentiated carcinoma warrants aggressive treatment at the time of diagnosis. PMID- 2206465 TI - Kinetics of isoniazid transfer into cerebrospinal fluid in patients with tuberculous meningitis. AB - For the pharmacokinetic analysis of isoniazid transfer into CSF, steady-state isoniazid concentrations of plasma and CSF were measured in eleven tuberculous meningitis patients confirmed with findings of CSF and neuroimazing. Peak plasma levels (4.17-21.5 micrograms/mL) were achieved at 0.25 to 3 hours after multiple isoniazid dose (600 mg/day). Terminal half-life, total clearance (CI/F) and volume of distribution (Vd/F) were 1.42 +/- 0.41 hr, 0.47 +/- 0.22 L/kg/hr and 0.93 +/- 0.48 L/kg, respectively. Isoniazid concentrations in CSF collected intermittently were highest at 3 hr (Mean, 4.18 micrograms/mL) and were 0.54 +/- 0.21 micrograms/mL at 12 hrs after the last dose of isoniazid 10 mg/kg/day. CSF/plasma partitioning of isoniazid and equilibration rate were estimated using modified pharmacokinetic/pharmacodynamic model. Disposition rate constant from CSF to plasma and CSF/plasma partitioning ratio of isoniazid were estimated to be 0.39 h-1 and 1.17, respectively. PMID- 2206467 TI - A case of idiopathic fibrosing pancreatitis. AB - We experienced a case of chronic fibrosing pancreatitis in an 18/12-year-old girl, which was idiopathic because there were no familial back ground, no cystic fibrosis of pancrease, no ductal anomalies and obstruction. The patient presented intermittent colicky abdominal pain and progressive obstructive jaundice, but T tube drainage and removal of the lymph nodes around the common bile duct relieved her symptoms and disease process. This seems to be the first case reported in a Korean child. Idiopathic fibrosing pancreatitis should be considered in the differential diagnosis of abdominal pain with obstructive jaundice in children. PMID- 2206468 TI - Biovars of coagulase-positive staphylococci isolated from bovine mastitic milk. AB - Fifty strains of coagulase-positive staphylococci associated with bovine mastitis were biotyped. Of them, 20 were identified as biovar C (cattle & sheep), 17 as biovar B (poultry & swine), 2 as biovar D (hares) and 1 as biovar F (pigeon & fox). Of the remaining strains, 2 were closely related to human biovar A, 2 failed one property to be classified as biovar B, 3 shared properties of biovars B and D and 3 could not be identified. Bovine strains belonging to biovar C formed an heterogeneous group showing differences in crystal violet growth type and production of alpha haemolysin. Only strains associated with biovar A were Tween 80 positive. The highest incidence of lytic reactions amongst all biovars was with phages 42 E (III) and 102 (IV). Antibiotic resistance was most frequently found in biovar C (65%). The 2 strains in biovar D, one classed as biovar C and one as intermediate, were enterotoxigenic (C or D toxins). PMID- 2206469 TI - Utilization of beet molasses for sterol production by some moulds. AB - Different moulds were cultivated in beet molasses (BM)-containing medium. Penicillium crustosum Thom was superior to the other moulds in total sterols production (4% on dry weight basis), efficiency of convertibility of the BM sugars to sterols (2%), total lipids (19.4%) and unsaponified lipids (13.4%). The treatment of BM with H2SO4- followed by centrifugation allowed maximum fermentation yields. The highest unsaponified lipids (16.5%) and total sterols level (7.4%) were obtained with a medium composed of (g/1): NaNO3, 3; K2HPO4, 3; MgSO4.7H2O, 1.5; K2SO4, 0.11; ZnSO4.7H2O, 0.05; FeCl3.6H2O, 0.16; H2SO4-treated BM, 60. Maximal sterol yields (8.4%) and high growth rate were achieved at the accelerated growth phase (8 days old cultures), when the initial pH value of the medium was adjusted to 7.0. PMID- 2206470 TI - Plasmid profiles as an epidemiological marker for Salmonella enterica serotype Enteritidis foodborne outbreaks. AB - The incidence of enteritidis serotype of Salmonella enterica in salmonellae infections has steadily increased in Spain from 27.1% in 1982 up to 63.4% in 1987. Given this high incidence, we have studied the plasmid profiles of Enteritidis isolates to subclassify them. Different profiles were observed in 50 isolates. In 13 Enteritidis serotype outbreaks, up to 5 different plasmid profiles were found. Each outbreak correlated with a single plasmid profile except in one case where plasmids of two different profiles were observed in strains from the same outbreak. PMID- 2206471 TI - Establishing pediatric cancer nursing research priorities: a Delphi study. AB - The purpose of this study was to have pediatric oncology nurses identify and rate topic priorities for clinical nursing research in the specialty and to determine if nurses in a pediatric cancer center identified different priorities than did nursing colleagues in other settings. The sample consisted of 44 nurses from a comprehensive pediatric cancer center and 43 nurses attending the 12th Annual APON Conference. A decision-making method, the classical Delphi technique, was used. Three rounds of soliciting opinions by questionnaires were completed, and data from each round were reviewed and categorized by a research team of six nurses until group consensus was achieved. The majority of priorities identified by both groups concerned nursing procedures, the pediatric oncology patient, and the specialty itself. The least number of priorities were in the categories of care delivery systems and families. One difference between the two groups was that professional issues dominated the cancer center sample, whereas psychosocial issues were more prominent in the APON sample. PMID- 2206472 TI - Rationale and development of an institutional pediatric chemotherapy certification course. AB - In a large pediatric teaching hospital located in the southwestern part of the United States, few nurses had participated in a formal program that taught the knowledge and skills required for the nurse to care for the patient receiving chemotherapy. In order to enhance the necessary clinical competency of the nursing staff, a Chemotherapy Certification Course was developed for this institution. In reviewing the literature there was minimal information on how to develop such a program. The purpose of this article is to describe the development of this course with the intent that it can serve as a guide in facilitating and implementing such a course in other institutions. As more hospitals adopt institutional certification as a form of continuing education in cancer nursing, perhaps the gap between knowledge and practice will decrease. The institutional certification course will be a significant step toward improving the level of practice of nurses caring for patients receiving chemotherapy. The goal of promoting professional competence will benefit the nurse, the institution, and patients and their families. PMID- 2206473 TI - Problems of instrument selection. AB - There are many problems in selecting appropriate instruments to use in research with children. Four problem areas have been outlined: instrument sensitivity, data source (adult report or observation v child self-report), adaptability to different ages and developmental levels, and the context or setting. PMID- 2206474 TI - Idarubicin. PMID- 2206475 TI - Painless port access. PMID- 2206476 TI - Duplicate publication--a serious concern. PMID- 2206477 TI - Pediatric pain assessment: trends and research directions. PMID- 2206478 TI - "Don't bump my bed, don't touch my feet". PMID- 2206479 TI - The effects of group therapy on siblings of pediatric oncology patients. AB - The stress and psychological difficulties of siblings of children with cancer is well documented. Siblings must cope with a myriad of emotions, isolation from the family, and many changes in daily life. Therefore, a need exists to determine the effects of psychosocial interventions on siblings of cancer patients. The support group is one psychosocial intervention that has been suggested as a method to relieve stress and enhance coping. A quasi-experimental design was selected to determine the effects of participation in a support group on the social adjustment of siblings of children with cancer. Conclusions suggest that a support group provides siblings with the opportunity to decrease their sense of isolation, ventilate negative feelings, and learn from each other. Additionally, descriptive data suggest a need for ongoing follow-up with siblings to help them manage the stresses emerging from the impact of the diagnosis and treatment on the family. Implications of this study suggest that nurses should organize support groups for siblings and/or refer them to existing groups. Also, this study suggests the need to work with siblings and educate parents regarding sibling concerns. PMID- 2206480 TI - A probability representation for phase information from multiwavelength anomalous dispersion. AB - A probability distribution function, cast in the representation of Hendrickson & Lattman [Acta Cryst. (1970), B26, 136-143], has been derived for the phase information from measurements of multiwavelength anomalous diffraction (MAD). This probability function readily permits one to determine figure-of-merit weights similar to those used in isomorphous replacement, and the coefficients that characterize this distribution function facilitate the combining of MAD phasing with results from other sources of phase information. This probability representation was derived in the course of a structural analysis of selenobiotinyl streptavidin from MAD data and applications have also been made in the structure determinations of interleukin-1 alpha and a drug complex with brominated DNA. PMID- 2206481 TI - Direct methods with single isomorphous replacement data. I. Reduction of systematic errors. AB - The direct-methods procedure for single isomorphous replacement (SIR) data [Hauptman (1982). Acta Cryst. A38, 289-294], as modified by Fortier, Moore & Fraser [Acta Cryst. (1985), A41, 571-577] has been implemented and tested with a large number of known structures. It was found that the modified procedure greatly reduces the bias toward 'unresolved' SIR invariant values associated with estimates of 0 or pi, but does not remove it entirely. If the heavy atoms are not in a centrosymmetric array the centroid of the distribution of invariant estimates is not centered on true protein values, but is biased toward conventional SIR values by up to 15 degrees, thus errors in the estimates are not random but systematic. When the heavy atoms are in a centrosymmetric array (or single heavy-atom site in space group P21), the distribution of estimates is often sharply bimodal, with peaks centered at both true invariant values and pure 'unresolved' SIR values. Simple procedures are given which can be applied in both situations to reduce significantly the bias with no overall loss of accuracy. An additional correction factor is then described which can be used to remove nearly all of the bias, and improve the accuracy as well. The result is that errors in the corrected invariant estimates are small in magnitude, but are now also random instead of systematic. Since the number of estimates greatly exceeds the number of phases, the remaining random errors should have little impact in phasing processes. PMID- 2206482 TI - Slow-cooling protocols for crystallographic refinement by simulated annealing. AB - An improved protocol for crystallographic refinement by simulated annealing is presented. It consists of slow cooling starting at high temperatures. Tests of refinements of aspartate aminotransferase and procin pepsin show that the slow cooling protocol produces lower R factors and better geometry than other protocols previously published. The influence of the temperature-control method, weighting, cooling rate and duration of the heating stage on the success of the slow-cooling protocol is studied. Analysis of the time course of the potential energy fluctuations indicates no global changes in the state of order of the system. Fluctuations of the potential energy are interpreted as localized conformational changes during the course of the refinement. PMID- 2206483 TI - Direct solution of continuous densities given the Fourier magnitudes. AB - In order to apply direct methods routinely to macromolecular crystals it will be necessary to generate a non-atomic theory which is applicable to continuous densities. Reformulation of the 'phase problem' in terms of deconvoluting an autocorrelation function or Patterson synthesis reduces the problem from a theoretically intractable transcendental problem to a system of simultaneous quadratic equations. These quadratic equations may, in principle, always be solved by conjugate direction search techniques. The phase problem is shown to be a class P problem, admitting a deterministic solution in polynomial time. Two algorithms are presented with running times proportional to N2points and Npoints log Npoints per step. These algorithms are a pixel-by-pixel search and a conjugate gradients search. When the data are exact and complete the Fourier magnitudes are readily inverted by them to find the image. An example with real data, from a 15mer of DNA, is also shown. PMID- 2206485 TI - Determination of the correct reference frame from an atomic coordinate list. AB - A simple method is described for determining the reference coordinate system of a list of atomic coordinates. The reference system is characterized by finding the optimal metric tensor on the basis of the expected bond lengths. The ability to identify the correct frame of reference is important for structures solved in non orthogonal unit cells. PMID- 2206484 TI - [Delimiting the molecular envelope of a protein by deconvolution of the Patterson function for native proteins]. AB - A process, based on the superposition method, is described to delimit the molecular envelope of a protein by deconvolution of the Patterson function. The object is to obtain a preliminary set of phases from native structure-factor amplitudes with only native intensity data. The method has been tested with data from two immunoglobulin Fab fragments, Fab NEW and Fab R19.9. Several zones of resolution were explored. PMID- 2206486 TI - Calculation of the point-by-point error in protein crystallographic electron density functions. AB - In protein crystallographic studies, the mean-square error at each point in the electron-density function is given, in space group P1, by [formula: see text] Here, Fo is the observed structure-factor amplitude; m(h) exp [i alpha B(h)] = P[alpha(h)] exp (i alpha) d alpha is the weighted phase factor in the 'best' Fourier coefficient of Blow & Crick; m2(h) exp (i alpha 2) = P[alpha(h)] exp (2i alpha) d alpha is similar to a traditional second moment. P[alpha(h)] d alpha is the probability that the phase angle for a given reflection has value between alpha and alpha + d alpha. PMID- 2206487 TI - Influence of neonatally-administered monosodium glutamate on the neuroendocrine regulation of prolactin cell activity in adult Syrian hamsters. AB - The effects of MSG on PRL cell activity in hamsters was assessed by injecting either MSG (8 mg/g body weight) or saline into male and female hamsters on day 8 of the neonatal period. One-hundred and three days later, the anterior pituitaries were removed for the analysis of PRL synthesis and storage. Serum PRL levels were also determined by radioimmunoassay as an index of in vivo PRL secretion. Blood levels of PRL were decreased by 74% in female and 88% in male hamsters treated with MSG as compared with vehicle controls. In females, glutamate induced a drop in PRL storage (90%) and synthesis (82%) while in male animals glutamate caused a non-significant decrease in PRL storage (48%) and synthesis (31%) as compared with controls. These results indicate that MSG induced arcuate nucleus lesions inhibit PRL cell activity in the hamster. PMID- 2206488 TI - Biomaterials for implanted closed loop insulin delivery system: a review. AB - The potential of five different groups of materials--carbons, glass and ceramics, polymers, hydrogels and collagen--as biomaterials in artificial implant applications is examined. In addition to the physical and/or structural properties of these materials, the blood and tissue responses to implants made of these biomaterials for various applications are presented. Emphasis is placed on materials related to the intended application; as catheter tips and biosensors for glucose to be used in conjunction with an implantable insulin delivery system as a complete artificial pancreas. PMID- 2206490 TI - An extracellular microelectrode array for monitoring electrogenic cells in culture. AB - This paper describes a planar array of microelectrodes developed for monitoring the electrical activity of cells in culture. The device allows the incorporation of surface topographical features in an insulating layer above the electrodes. Semiconductor technology is employed for the fabrication of the gold electrodes and for the deposition and patterning of an insulating layer of silicon nitride. The electrodes have been tested using a cardiac cell culture of chick embryo myocytes, and the physical beating of the cultured cells correlated with the simultaneous extracellular voltage measurements obtained. It was found that extracellular stimulation of the cells was possible via the same electrodes used for recording. PMID- 2206489 TI - Miniaturization of a liquid membrane sensor for the determination of bile acids. AB - The preparation of a compound liquid ion exchanger used for the miniaturization of bile acid sensitive microelectrode is described. The liquid ion exchanger is 2% benzyldimethylhexadecylammonium cholate in decanol/0.1 M hexadecyltributylammonium taurocholate in 5% hexachlorobenzene, 0.5% bromoacetanilide O-dichlorobenzene. The slopes, detection limits, selectivity coefficients, drifts and response time of the various bile acid sensitive microelectrodes are evaluated and compared. PMID- 2206491 TI - Oscillometric instrument for the non-invasive detection of low-level microbial activity. Part 2: Growth characteristics, detection limits and impedimetric assays. AB - Instrument performance and application was evaluated with a variety of microbial suspensions. Data were compared with those obtainable from current commercial apparatus in terms of resolution and detection times. Trials with growing and non growing cultures indicated periodic synchronous ion exchange processes. Media composition, particularly salt and nutrient ratios, remain crucial to early and rapid detection of viable microbial activity at low concentrations. With appropriate conditions very significant improvements in detection times with typical detection thresholds of 300 min for start concentrations of 10(2) are shown. It is concluded that with regard to resolution and stability, the system out-performs current systems and is superior in terms of potential test costs, sample handling and sample transport. PMID- 2206492 TI - A swellable polymer as carbamazepine dissolution rate enhancer. AB - A superdisintegrant (cross-linked sodium carboxymethylcellulose, Ac-Di-Sol was used for the enhancement of the dissolution rate of carbamazepine, an anti epileptic drug characterized by very low water solubility. Three different drug/polymer systems were prepared: a physical mixture and two loaded systems obtained using a solvent evaporation method and a spraying method. In vitro dissolution tests showed that the dissolution rate in water of carbamazepine from all the systems prepared (compared with that of the pure drug) always increases, particularly in the case of the physical mixture and of the loaded system obtained with the spraying method, while DSC analysis shows that no drug amorphisation has occurred. PMID- 2206493 TI - [1992: the target or start of a new course for pharmacy?]. AB - Problems related with EEC pharmaceutical market post-1992 are discussed. Particular attention was drawn on the future system for the authorization of medicinal products in the European Community and its new price policy. PMID- 2206494 TI - Osteoinductive implants in head and neck surgery. PMID- 2206495 TI - Lasers and wound healing. PMID- 2206496 TI - Message from the National Institutes of Health. The state of the National Institute on Deafness and Other Communication Disorders. PMID- 2206497 TI - Management of the aging forehead. AB - Browlifting and forehead procedures are a critical element in the contemporary surgical management of the aging face. Esthetics of the upper third of the face will dictate brow position and its relationship to the supraorbital rim and eyes. Treatment of deformities of the upper third of the face can be varied according to the sex and age of the patient as well as contour of the hairline and forehead. The indications, advantages, disadvantages, and techniques of the coronal forehead, modified pretrichal forehead, midforehead, and direct browlifting procedures are discussed. PMID- 2206498 TI - The role of bacterial adherence in otitis media with effusion. AB - Adherence of nontypable Haemophilus influenzae and Streptococcus pneumoniae to nasopharyngeal epithelial cells was investigated in vitro. Both strains had higher affinity to the epithelial cells of children than to those of adults. In children, the adherence was significantly greater in patients with otitis media with effusion than in normal subjects. Secretory IgA in nasopharyngeal secretions was found to have antibody activity against the bacteria. Adherence of both bacteria was significantly smaller in the group having secretory IgA antibody activity than in the group having no activity. These results suggest that bacterial adherence to the nasopharynx may play an important role in the pathogenesis of otitis media with effusion in children, and that secretory IgA in nasopharyngeal secretions may be related to the decrease of adherence. PMID- 2206499 TI - Tissue expansion of the head and neck. Indications, technique, and complications. AB - Tissue expansion is indicated in the reconstruction of various defects of the head and neck in instances where there is inadequate adjacent tissue to allow either primary closure of the defect or repair with a local flap. It may also be indicated in instances where repair of a defect by an alternative method such as a local, regional, or distant flap will result in an unacceptable donor or recipient site deformity. Although tissue expansion is simplistic in concept, it does require judgment and indepth preoperative planning to ensure optimal results. The complication rate is high for tissue expansion in the head and neck, particularly in the cheek and neck area. Despite the frequency of complications, in the vast majority of cases the intended reconstruction is successful. PMID- 2206500 TI - Augmentation mentoplasty using Mersilene mesh. AB - Many different materials are available for augmentation mentoplasty. However, the optimal implant material for chin implantation has yet to be found. During the past several years, a number of experienced surgeons have turned to the use of Mersilene mesh. Mersilene mesh is a non-absorbable Dacron polyester fiber that can be conformed easily into layers to achieve tailored dimensions and shape. At the McCollough Plastic Surgery Clinic PA, Birmingham, Ala, 277 patients over a 10 year period underwent chin augmentation with Mersilene mesh implants. The material provides excellent tensile strength, durability, and surgical adaptability. The overall complication rate was 3.2% (nine patients); infection rate, 2.5% (seven patients); and removal secondary to infection, 1.7% (five patients). Based on this 10-year experience, Mersilene mesh remains our material of choice for chin augmentation. PMID- 2206501 TI - Salivary gland cancer. A case-control investigation of risk factors. AB - Unlike most upper aerodigestive tract cancers, salivary gland cancers are relatively infrequent, are characterized by a diversity of histologic subtypes, and have never been etiologically associated with tobacco exposure. We present the results of a case-control study of risk factors for these cancers, with risk estimates derived from self-administered comprehensive risk-factor questionnaires distributed to patients at The University of Texas M. D. Anderson Cancer Center, Houston. Cases were 64 patients with histologically confirmed salivary gland cancer. Control subjects, randomly selected from the same patient population excluding patients with cancer of the head and neck or nonmelanoma skin cancer, were frequency-matched to the cases by age, sex, and ethnicity to achieve a 2:1 control subjects/cases ratio. On multivariate analysis, prior radiotherapy was a significant risk factor for both men (odds ratio [OR] = 2.1) and women (OR = 2.3). Among women, higher educational attainment (OR = 2.4), alcohol use (OR = 2.0), and hairdye use (OR = 2.5) were also significantly associated with risk. There were no significant differences between cases and control subjects with respect to tobacco exposure or specific occupational or leisure-time exposures. There is biological plausibility for associations with hairdye use and alcohol exposure. PMID- 2206502 TI - Cisplatin-fluorouracil interaction in a squamous cell carcinoma xenograft. AB - Patients with squamous cell carcinoma of the head and neck are treated with cisplatin and fluorouracil according to a schedule based on the findings of clinical studies. A similar schedule showed a supra-additive effect in the treatment of xenografted human squamous cell carcinoma of the head and neck. We sought to ascertain whether this schedule was optimal. A single intraperitoneal injection of cisplatin (7.5 mg/kg) was combined with three injections of fluorouracil given during a 24-hour period (total dose, 150 or 80 mg/kg) before, during, or after cisplatin administration. The combined effect of cisplatin and fluorouracil on tumor growth and toxic effects was schedule dependent. Consideration of both toxic effects and tumor growth inhibition, as assessed by reduction of the area under the growth curve, the optimal administration interval was found to be fluorouracil given 3 days after cisplatin administration. PMID- 2206503 TI - HLA class I and class II antigen expression on squamous cell carcinoma of the head and neck. AB - We compared human major histocompatibility (HLA) class I and class II antigen expression on squamous cell carcinoma of the head and neck with that on normal mucosa. Frozen sections of a consecutive series of 30 squamous cell carcinomas were stained with the monoclonal antibodies W6/32 (class I) and anti-DR (class II) using an immunoperoxidase technique. Normal mucosa showed class I and class II expression in the basal layers only. Class I expression on tumors was diffuse in 87%, patchy in 10%, and scattered in 3%. Class II expression on tumors was diffuse in 20%, patchy in 53%, scattered in 20%, and absent in 7%. Patterns of expression did not correlate significantly with clinical parameters, including survival, except that class II diffuse and patchy patterns were found to correlate with more poorly differentiated tumors. PMID- 2206504 TI - Transtympanic endoscopic findings in patients with otitis media with effusion. AB - Using a fine, rigid endoscope (Olympus, SES-1711K), we examined the middle ear, including the tympanic orifice of the eustachian tube, of children with otitis media with effusion (OME) in its active stage (26 ears), in the convalescent stage (13 ears), and during treatment with ventilation tubes for 10 days to 6 months (five ears) through myringotomy with the patients under general anesthesia. Several color photographs of representative ears are shown. In the active stage of OME, edema (73.1%) and hyperemia (23.1%) were characteristic features of the middle ear mucosa, and normal mucosa was seen in only one ear (3.1%). The tympanic orifice of the eustachian tube, which could be examined in 12 ears, were stenosed with edema in four ears (33.3%) or plugged with effusion in three ears (25.0%) in this group. In the convalescent stage of OME, dilated vessels were most often seen (69.2%), but the rest of the patients had normal mucosa (30.8%) in the middle ear, and none of them had edema nor hyperemia. The tympanic orifice of the eustachian tube, which could be examined in five ears, was clearly patent in all the patients in this group. One ear that was treated with a ventilation tube for 1 month showed dilated vessels and less severe inflammation than did ears that were in the active stage of OME, and three ears that were treated for more than 3 months showed almost normal middle ear mucosa. PMID- 2206505 TI - Computed tomography of metastatic cervical lymph nodes. A clinical, computed tomographic, pathologic correlative study. AB - A retrospective comparative study of 63 neck dissections was undertaken to evaluate further the accuracy of high-resolution computed tomography (CT) in the detection of nodal metastases, as previous studies have indicated a trend toward the superiority of CT scanning over palpation. The respective values of neck examination, CT scanning, and histopathologic examination were assessed in 51 patients with head and neck cancer who underwent a total of 63 neck dissections. The overall agreement between clinical examination findings and histopathologic findings was 92% vs 81% for CT scanning. A retrospective analysis of the CT findings failed to reveal greater accuracy. We found nodes measuring 10 mm or more with central low density always to be malignant. Because CT scanning seems to offer little advantage over palpation in the nonirradiated neck, it should not be regarded as an essential tool in the staging of nodal disease. After radiation therapy, as neck dissection is only performed because of clinical or radiologic suspicion, CT scanning is of utmost importance. PMID- 2206506 TI - A survey of accessory auricle anomaly. Pedigree analysis of seven cases. AB - We performed an investigation of 50 accessory auricles on subjects encountered during 1983 through 1985. Fifteen of the families were found to have the same accessory auricular deformity among the probands' family members. From these 15 families, we selected seven pedigrees that were not accompanied by auricular deformities who had filial generations for analysis. Pedigrees 1 through 6 showed autosomal dominant inheritance; two also had irregular dominant properties (pedigrees 4 and 7), and one (pedigree 7) could not be excluded from the possibility of having an X-linked recessive inheritance. During the investigation, there were latent accessory auricles in which the cartilages were seen to be subcutaneous only or protruding slightly. Genetically, the pathogenesis of an accessory auricle should be related to the accessory auricular gene. PMID- 2206507 TI - Significant premaxillary augmentation. AB - Substantial premaxillary augmentation is necessary as an adjunctive treatment in most cleft rhinoplasties and in those patients exhibiting an acute nasolabial angle due to retrusion of the premaxila. We describe our technique of evaluation and treatment of this condition using a custom-carved piece of material made from a woven combination of Teflon and organic fibers (Proplast). Detailed technical illustrations as well as patient results are demonstrated. We have found this technique in our hands to be a simple, safe, and effective means of correction of significant premaxillary retrusion. PMID- 2206508 TI - Pseudocyst of the auricle. Case report and world literature review. AB - We treated a patient with pseudocyst of the auricle and reviewed the 113 cases previously published in the world literature. Pseudocyst of the auricle is an asymptomatic, noninflammatory cystic swelling that involves the anthelix of the ear, results from an accumulation of fluid within an unlined intracartilaginous cavity, and occurs predominantly in men (93% of patients). Characteristically, only one ear is involved (87% of patients), and the lesion is usually located within the scaphoid or triangular fossa of the anthelix. Previous trauma to the involved ear is uncommon. The diagnosis may be suggested by the clinical features, and analysis of the aspirated cystic fluid and/or histologic examination of a lesional biopsy specimen will confirm the diagnosis. Therapeutic intervention that maintains the architecture of the patient's external ear should be used in the treatment of this benign condition. PMID- 2206509 TI - Functional upper airway obstruction in adolescents. AB - Functional upper airway obstruction is an uncommon manifestation of a conversive reaction characterized by recurrent stridor attacks caused by adduction of the vocal cords during inspiration. The oxygen saturation never drops to pathologic levels. The stridor is not accompanied by an appropriate degree of anxiety and is not associated with other symptoms. Patients benefit from verbal reassurance and speech therapy, but stridor attacks tend to recur and psychiatric consultation seems necessary in most cases. We present the case histories of three adolescent patients with nonorganic upper airway obstruction and describe the features that may facilitate the diagnosis of this condition. Early diagnosis and intervention may prevent unnecessary and potentially harmful investigations and therapy. PMID- 2206510 TI - Multiple intracranial mucoceles associated with phaeohyphomycosis of the paranasal sinuses. AB - The purpose of this article is to alert clinicians to a new pathogenic fungus of the paranasal sinuses called Exserohilum rostratum. Exserohilum species are one of the etiologic agents of phaeohyphomycosis, a constellation of entities caused by dematiaceous fungi. This class of fungal sinus infection has emerged only in the past decade; it occurs primarily in immunocompetent individuals and produces a tenacious, progressive pansinusitis. To our knowledge, this study describes the first case of multiple intracranial mucoceles secondary to E rostratum. The diagnostic workup includes computed tomography and magnetic resonance imaging followed by direct microscopic examination of tissue biopsy specimens. A craniotomy followed by a bilateral external ethmoidectomy was necessary for complete extirpation of the infected mucoceles. Aggressive surgical management of this mycotic infection is described. PMID- 2206512 TI - Fluoride therapy for otosclerosis. PMID- 2206511 TI - Osteoma of the middle ear. Report of a case. AB - Osteomas of the middle ear are rare. We report a case of a 7-year-old boy with osteoma originating from the pyramidal eminence, combined with congenital cholesteatoma. The osteoma and cholesteatoma were successfully removed by tympanomastoidectomy. The long process of the incus and the superstructure of the stapes disappeared. The body of the incus was sculpted and used as a columella. Histopathologically, the osteoma was much the same as an external auditory canal osteoma. The possibility of a primary congenital origin of this neoplasm is suggested. PMID- 2206513 TI - Immunity to mycobacteria: possible role of alpha/beta and gamma/delta T lymphocytes. AB - Immunity to pathogenic mycobacteria is mediated by T lymphocytes. The possible contribution of CD4 alpha/beta T cells, CD8 alpha/beta T cells and gamma/delta T cells as well as the possible role of interleukin-mediated macrophage activation and target cell lysis through direct cell contact is discussed. Furthermore, attempts to define mycobacterial antigens for T lymphocytes with particular emphasis on heat shock proteins are described. The data currently available suggest complex interactions between different T-cell types in immunity to mycobacteria. PMID- 2206514 TI - Human-human hybridoma producing monoclonal antibodies against colorectal cancer associated antigens. AB - Lymphocytes from lymph nodes draining the tumor region in patients with colorectal cancer were fused with two different human B-lymphoblastoid cell lines, LICR-LON-HMy-2 (HMy-2) and WI-L2-729-HF2 (729-HF2), to generate hybridomas synthesizing antibodies reacting with tumor-associated antigens. In this way 220 hybridomas were obtained which produce antibody reacting with colon cancer cells. All established clones produced IgM. Four human monoclonal antibodies have been further analyzed. The cell lines producing these antibodies are all hybrids based on DNA analysis. Three of the antibodies (G4146, B9165 and D4213) showed binding to differentiation antigens by immunocytochemical analysis on different cancer cell lines and normal human leucocytes and by immunohistochemical analysis on sections of frozen malignant and normal tissues, while the fourth (F11348) showed a reaction with all cells and tissues tested. Western blots of tumor extracts showed binding of G4146 to two components from colon cancer cells with Mr of 59 K and 61 K, while B9165 bound to a 43 K component and F11348 to several components with Mr from 30 to 200K. D4213 showed no binding in this analysis. The results obtained demonstrate the successful application of hybridoma technology to produce human monoclonals with reactivity to differentiation antigens. PMID- 2206515 TI - Melanotic schwannoma of the orbit. Immunohistochemical and ultrastructural study of a case and survey of the literature. AB - Light microscopical, immunohistochemical and ultrastructural study of a case of melanotic (pigmented) schwannoma in the left orbit of a 22-year-old man is presented. The tumour caused exophthalmus for three months and was located under the eyeball. Partial removal resulted in recurrence after three years. The recurrent tumour with extension to the nasal cavity and maxillary sinus was extirpated without loss of vision, and a year later the patient was without symptoms. The tumour tissue was Fontana positive, could be bleached, and showed immunoreactivity for S-100, vimentin and HMB 45. Ultrastructurally, the tumour cells, particularly the pigment loaded cells, showed a varying amount of basal lamina at the surface, melanosomes in varying stages of melanization, fine cytoplasmic filaments and micropinocytotic vesicles. Survey of the literature and discussion of the melanogenesis in Schwann's cells are presented. PMID- 2206516 TI - Ossification in nude mice. 1. Macroscopical study. AB - Ossification was studied in cleared fetuses, newborns, 1- and 6-week-old nu/nu and nu/+ mice of the B 10 LP background. The same ossification pattern was observed in nu/nu and nu/+ in the embryonal period as well as in newborn animals and mice aged 1 or 6 weeks. On the other hand, 6-week-old nu/nu mice exhibited a lower X-ray density of the skeleton and a lower thickness of the proximal tibial growth plate than 6-week-old nu/+ litter mates. The results indicate the influence of postnatal factors on the skeletal development of nu/nu mice. PMID- 2206517 TI - The prevalence of plasmids in Danish bovine and human isolates of Salmonella dublin. AB - Nine different plasmid profiles were demonstrated among 135 Danish isolates of Salmonella dublin, with 58% of the strains enclosed in the major profile group. Two strains did not carry any plasmids. The plasmid profiles of 129 strains (96%) were made up of one or more of only four plasmids of approximate sizes 98 kb, 80 kb, 4.0 kb, and 3.8 kb. There was no significant difference in the prevalence of different plasmid profile groups between isolates from cattle and man. The serovar-specific and virulence-associated 80 kb plasmid could be demonstrated in all plasmid carrying strains, but one strain carried this plasmid at a very low copy number. Five of 47 strains tested showed resistance to antibiotics (2 to sulphathiazole, 2 to streptomycin, and 1 to streptomycin and tetracycline). Only the combined streptomycin/tetracycline resistance was transferable by a 48 kb conjugative plasmid. PMID- 2206518 TI - In vitro activity of 9 antimicrobial agents against 177 strains of Haemophilus influenzae isolated from hospitalized patients. AB - In vitro activity of 4 commonly used and 5 new antibiotics was examined against 177 strains of Haemophilus influenzae. All strains were collected from various sites in patients with clinical infections. The study confirms that several newer antibiotics are useful alternatives to older drugs, as measured by in vitro activity. Ciprofloxacin and ofloxacin were the most active agents, (MIC90 0.012 micrograms/ml and 0.05 micrograms/ml respectively), followed by aztreonam (MIC90 0.1 micrograms/ml) and cefuroxime (MIC90 0.8 micrograms/ml). A new macrolide, azithromycin (CP 62,993), was more active than erythromycin, MIC90 1.6 micrograms/ml vs 6.4 micrograms/ml. Beta-lactamase production was detected in 4.5% (8/177) of the strains. In vitro activity was the same against strains collected in 1985 and 1988. No increase in beta-lactamase production was recorded. PMID- 2206519 TI - Histological study of the regrowth of a human melanoma xenograft exposed to single dose irradiation. AB - The aim of this investigation was to find the location and the histological characteristics of cells that were the source of tumour regrowth after single dose irradiation. A human melanoma xenograft was irradiated with a single dose of 25.0 Gy which gives local tumour control in nearly 50% of treated animals. Serial histological sections were made from tumours removed during the first two weeks after irradiation. During the first week the perivascular organization of tumour parenchyma disappeared and the central part of the tumour became necrotic. The occurrence of vascular stasis, thrombosis and endothelial cell changes indicated that radiation injury to the vascular system was involved in the disappearance of the tumour cords. Tumour cells that remained histologically intact were located in subcapsular areas. The incidence of normal mitotic figures increased, and the fraction of abnormal mitoses and the incidence of micronuclei decreased 5 to 7 days before macroscopical regrowth was usually detected. It is concluded that cells which are the source of tumour regrowth were located in the subcapsular areas at the time of irradiation. Radiation injury to the tumour vascular system was an important factor in the necrotization of the tumour centre after treatment. PMID- 2206520 TI - Considerations in the use of processed resilient denture liner. PMID- 2206521 TI - Dental staff manpower in Wisconsin. PMID- 2206522 TI - Dental auxiliary education. PMID- 2206523 TI - Cellular response to different viscosities of liquid silicone in the rat peritoneal cavity. PMID- 2206524 TI - Effects of artificial cranial deformation on human mandibular form. PMID- 2206526 TI - In vitro micro-leakage of composite resin systems in dentin using a uniform cavity preparation. PMID- 2206525 TI - Glass temperatures in posterior composites and their resins. PMID- 2206527 TI - Localization of the subcellular distribution of the protein kinases catalyzing the phosphorylation of extracellular matrix proteins. PMID- 2206528 TI - Expression of hemidesmosome antigens in cultured corneal epithelial cells. PMID- 2206529 TI - [Silver amalgam surfaces on provisional dentures]. PMID- 2206530 TI - A monoclonal antibody that defines rostrocaudal gradients in the mammalian nervous system. AB - Spinal cord axons display a rostrocaudal, positional bias in their innervation of sympathetic ganglia and intercostal skeletal muscles. In an effort to examine the molecular basis of this positional specificity, we used the cyclophosphamide immunosuppression method to produce monoclonal antibodies that bind preferentially to rostral ganglia. The staining distribution of one of these antibodies, ROCA1, has been analyzed using a novel histological method. A graded decline in binding is observed along the chain of adult rat sympathetic ganglia, as well as in the nerves innervating intercostal muscles. The antigen is identified on immunoblots as a 65 kd protein, whose distribution corresponds to the pattern found histologically. Surprisingly, ROCA1 appears to bind to glial cells, implying rostrocaudal, molecular differences in their surfaces. PMID- 2206531 TI - Alteration and restoration of K+ channel function by deletions at the N- and C termini. AB - Voltage-dependent ion channels are thought to consist of a highly conserved repeated core of six transmembrane segments, flanked by more variable cytoplasmic domains. Significant functional differences exist among related types of K+ channels. These differences have been attributed to the variable domains, most prominently the N- and C-termini. We have therefore investigated the functional importance of both termini for the delayed rectifier K+ channel from rat brain encoded by the drk1 gene. This channel has an unusually long C-terminus. Deletions in either terminus affected both activation and inactivation, in some cases profoundly. Unexpectedly, more extensive deletions in both termini restored gating. We could therefore define a core region only slightly longer than the six transmembrane segments that is sufficient for the formation of channels with the kinetics of a delayed rectifier. PMID- 2206532 TI - Two components of high-threshold Ca2+ current inactivate by different mechanisms. AB - High-threshold Ca2+ current triggers neurotransmitter release, but the existence, significance, and correct identification of different types of high-threshold Ca2+ channels remain controversial. We show selective inhibition of a rapidly inactivating component of high-threshold Ca2+ current in rat sensory neurons by bursts of brief pulses that mimic trains of action potentials and by prolonged depolarization just above the normal rest potential. In contrast, a slowly inactivating component decreases only when sufficient Ca2+ accumulates within the cell. Thus, there are physiologically important differences: whereas availability of the transient component depends on the value of the rest potential and the pattern of a prior stimulus, the sustained component seems to provide a baseline level of voltage-dependent Ca2+ entry that is lost only when intracellular Ca2+ rises. PMID- 2206533 TI - Synaptoporin, a novel putative channel protein of synaptic vesicles. AB - By homology screening of a rat brain library, we have isolated cDNAs that encode a novel member of the synaptophysin/connexin channel protein superfamily. The deduced protein, named synaptoporin, displays 58% amino acid identity to synaptophysin, with highly conserved transmembrane segments, but a divergent cytoplasmic tail. Northern blot analysis and PCR amplification of RNA from different rat tissues indicate expression of synaptoporin transcripts in the CNS. Antibodies against a synthetic peptide or a fusion construct encompassing the cytoplasmic tail region of synaptoporin detect a polypeptide of 37 kd that copurifies with small synaptic vesicles. Our data suggest the existence of a family of vesicular channel proteins whose members may be differently distributed among synaptic vesicle subpopulations. PMID- 2206534 TI - Macrophages can modify the nonpermissive nature of the adult mammalian central nervous system. AB - Although astrocytic gliosis has been linked to failure of axonal regeneration in the adult mammalian CNS, its role is not fully established. We used an in vitro assay to investigate the role of reactive astrocytes and macrophages in influencing axonal growth in the lesioned adult rat optic nerve. Soon after optic nerve transection, the nonpermissive nature of the optic nerve is altered to a permissive state near the lesion. This may account for injury-induced axonal sprouting and may contribute to the failure of these sprouts to elongate beyond the site of the lesion in vivo. We provide evidence that this lesion-induced change in the axonal growth-promoting properties of the CNS near the lesion may be produced by mononuclear phagocytes. In addition, several months after optic nerve transection, the degenerated nerves, which consist mainly of astrocytes and lack myelin, i.e., astrocytic "scar" tissue, are a good substrate for neurite growth. Taken together, these results suggest that in this in vitro system, substantial inhibitory effects are not associated with regions of astrocytic gliosis and that the nonpermissive nature of the CNS white matter can be modified by macrophages. PMID- 2206535 TI - Identification of cells in rat brain and peripheral tissues expressing mRNA for members of the nerve growth factor family. AB - Cells expressing mRNA for hippocampus-derived neurotrophic factor (HDNF/NT-3) or brain-derived neurotrophic factor (BDNF) were identified by in situ hybridization. In the rat brain, HDNF mRNA was predominantly found in pyramidal neurons in CA1 and CA2 of the hippocampus. Lower levels of HDNF mRNA were found in granular neurons of the dentate gyrus and in neurons of the taenia tecta and induseum griseum. BDNF mRNA-expressing cells were more widely distributed in the rat brain, with high levels in neurons of CA2, CA3, and the hilar region of the dentate gyrus, in the external and internal pyramidal layers of the cerebral cortex, in the claustrum, and in one brainstem structure. Lower levels were seen in CA1 and in the granular layer of the hippocampus, in the taenia tecta, and in the mammillary complex. In peripheral tissues, HDNF mRNA was found in glomerular cells in the kidney, secretory cells in the male rat submandibular gland, and epithelial cells in secondary and tertiary follicles in the ovary. Cells expressing BDNF mRNA were found in the dorsal root ganglia, where neurons of various sizes were labeled. PMID- 2206536 TI - Hemopoietic colony-stimulating factors: biologic functions and clinical potentials. PMID- 2206537 TI - Eosinophil colony-stimulating factor induced by administration of interleukin-2 into the pleural cavity of patients with malignant pleurisy. AB - Systemic administration of interleukin (IL)-2 to patients with malignant diseases induces peripheral eosinophilia. In the present study, to clarify the mechanism of eosinophilia induced by IL-2, we examined the changes in the number of eosinophils and eosinophil colony-stimulating factor (Eo-CSF) activity in the pleural fluids of six patients with malignant pleurisy caused by lung cancer or malignant mesothelioma during and after intrapleural administration of IL-2. Results showed that intrapleural administration of IL-2 induced marked eosinophilia in the pleural fluid and moderate eosinophilia in the peripheral blood, and that during IL-2 administration, marked Eo-CSF activity appeared in the pleural fluid before increase in the number of eosinophils, but that this activity did not appear in the peripheral blood. This Eo-CSF activity was inhibited by a combination of anti-IL-5 antibody, anti-IL-3 antibody, and anti granulocyte/macrophage colony-stimulating factor (anti-GM-CSF) antibody, but not by each antibody alone. Chemotactic activity for eosinophils was also detected in the pleural fluid during IL-2 treatment. These results suggest that eosinophilia in the pleural fluid induced by IL-2 injection into the pleural cavity of patients with malignant pleurisy is due to the Eo-CSF activities of various components, including IL-5, IL-3, and GM-CSF, and chemotactic factors for eosinophils induced locally in the pleural cavity by IL-2. PMID- 2206538 TI - Junctional adhesion mechanisms in airway basal cells. AB - The morphology of basal cells varies according to the height of the epithelium they are associated with. In taller epithelium, basal cells appear to have more tonofilaments (keratin filaments) than basal cells in shorter epithelium. We hypothesized that the changes in basal cell structure represent differentiation of junctional adhesion mechanisms related to the attachment strength necessary for the various-height epithelium. To evaluate this hypothesis, we used light- and electron-microscopic morphometry to quantitate junctional adhesion structures in basal cells from mice, rats, cats, rabbits, and sheep. The height of the tracheal columnar epithelium ranged from 12.0 microns in the mouse to 56.8 microns in the sheep. The volume density of basal cell keratin filaments ranged from 0.012 in the rat to 0.261 in the sheep and total desmosome length/basal cell profile (BCP) ranged from 0.08 microns to 1.77 microns, respectively. Total hemidesmosome length/BCP was similar in each airway sample. A close correlation was obtained between the height of the epithelium and the volume fraction of keratin filaments (r = 0.96) and total desmosome length/BCP (r = 0.94) in all airways studied. Total hemidesmosome length/BCP was not closely related to the height of the epithelium (r = 0.31). Based on these observations, we conclude that the basal cell is a differentiated cell with respect to junctional adhesion and a primary function of the airway basal cell is for attachment of columnar cells to the basal lamina. PMID- 2206539 TI - Hypoxia directly increases serotonin transport by porcine pulmonary artery endothelial cell plasma membrane vesicles. AB - To determine whether hypoxia has a direct effect on the plasma membrane transport of serotonin (5-HT), we measured 5-HT transport activity: (1) in plasma membrane vesicles isolated from normoxic and hypoxic endothelial cells, (2) in endothelial cell plasma membrane vesicles that were exposed directly to normoxia or hypoxia, and (3) in endothelial cell monolayers incubated in the presence of 1 x 10(-7) M cycloheximide and exposed to normoxia or hypoxia. A 24-h exposure of endothelial cells to hypoxia resulted in a 40% increase (P less than 0.005) in specific 5-HT transport by plasma membrane vesicles derived from these cells. When plasma membrane vesicles were isolated and then directly exposed to normoxia or hypoxia for 1 h at 37 degrees C, a 31% increase (P less than 0.005) in specific 5-HT transport was observed in hypoxic vesicles. Hypoxia did not alter the Km of 5-HT transport (normoxia = 3.47 microM versus hypoxia = 3.76 microM) but markedly increased the maximal rate of transport (Vmax) (normoxia = 202.4 pmol/min/mg protein versus hypoxia = 317.9 pmol/min/mg protein). Cycloheximide alone had no effect on 5-HT transport by normoxic endothelial cells but did block hypoxia induced increases in 5-HT uptake in endothelial cell monolayers exposed to 24-h hypoxia. These results indicate that hypoxia increases 5-HT transport in pulmonary artery endothelial cells by a direct effect on the plasma membrane, leading to an increase in the effective number of transporter molecules without alteration in transporter affinity for 5-HT, and possibly by an indirect effect involving de novo protein synthesis. PMID- 2206540 TI - Transforming growth factor-beta increases elastin production by neonatal rat lung fibroblasts. AB - While elastin degradation is a hallmark of pulmonary emphysema, it is likely that elastin synthesis also occurs. However, the supramolecular structure and function of the newly synthesized elastin are abnormal. Very little is known about the regulation of elastin synthesis during the development of emphysema when prominent collections of mononuclear phagocytes are found in and near the alveolar interstitium. Transforming growth factor-beta (TGF-beta) is an important regulator of collagen and fibronectin production in wound healing, which is also accompanied by an influx of mononuclear phagocytes. We hypothesized that TGF-beta may influence elastin production by fibroblasts in the pulmonary interstitium. Therefore, we examined the influence of TGF-beta on the production of elastin by postconfluent cultures of neonatal rat lung fibroblasts. Elastin production was quantitated by analyzing the incorporation of [3H]valine into the soluble elastin precursor tropoelastin (TE). The incorporation of [3H]valine into TE was approximately 2-fold greater in the presence of 40 or 100 pM TGF-beta than in its absence. The intracellular, free [3H]valine pool was increased by 18% in the presence of TGF-beta. Therefore, TGF-beta-related differences in the precursor pool size were not solely responsible for the observed increase in [3H]valine incorporation. Northern analysis demonstrated that the increase in TE was accompanied by a smaller but significant increase in the steady-state level of elastin mRNA. Thus, the observed increase in TE production can be at least partially attributed to a pretranslational effect of TGF-beta. PMID- 2206541 TI - Airway intra-luminal macrophages: evidence of origin and comparisons to alveolar macrophages. AB - Airway intra-luminal macrophages (AI-LM) are a little-studied subpopulation of pulmonary macrophages that are located on the surfaces of the conducting airways of the lower respiratory tract. In this study, we: (1) developed a flow cytometric approach by which AI-LM can be viably isolated in high purity from cell suspensions obtained by airway washings; (2) comparatively examined various functional, biochemical, biophysical, and morphologic features of the rat's AI-LM and alveolar macrophage (AM) phenotypes, and (3) investigated the origin of the AI-LM in the rat. Airway cells were harvested from the tracheas of adult Fischer 344 rats, and AM were obtained from the lungs by conventional bronchopulmonary lavage or via prosthetic airway circuits that supplanted the removed tracheas. Flow cytometric analyses of lavaged airway cells revealed that the AI-LM fell within the range of the electro-optical phenotype of AM, and subsequent cell sorting experiments demonstrated that virtually all viable AI-LM could be sorted from contaminating airway epithelial cells in greater than 95% purity based on their electro-optical characteristics, e.g., electronic volume, axial light loss, 90 degrees light scatter, and blue and green autofluorescence signals. In Fc gamma receptor-mediated phagocytic studies, approximately 90% of AM engulfed opsonized erythrocytes (EIgG) whereas only 60% of the AI-LM were able to do so. Comparisons of the numbers of EIgG in phagocytic AM and in phagocytic AI-LM indicated the AI-LM were less phagocytic. Densitometric analyses of sorted AI-LM and of sorted AM stained for acid phosphatase, nonspecific esterase, and beta glucuronidase indicated that the activities of these enzymes were generally less in the AI-LM than in the AM. Morphometric comparisons of sorted AM and of sorted AI-LM showed that the AI-LM were generally larger than the AM and that the surfaces and nuclei of the AI-LM were more regular than those of the AM. The AI LM were found to strongly label with the monoclonal antibody ED1, which recognizes an antigen on the surfaces of rat AM, but the AI-LM did not label with the monoclonal antibody ED2, which recognizes an antigen on the surfaces of rat peribronchial and pulmonary perivascular macrophages. Over the course of alveolar phase clearance of a lung burden of polystyrene microspheres, the frequency distributions of the particles in AI-LM and in AM were found to be virtually identical.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2206542 TI - Ultrasonic integrated backscatter two-dimensional imaging: evaluation of M-mode guided acquisition and immediate analysis in 55 consecutive patients. AB - We have shown previously that cardiac cycle-dependent integrated backscatter characterizes the physical state of myocardium in patients with ischemic heart disease and cardiomyopathy. In the present study the clinical applicability of M mode guided two-dimensional integrated backscatter imaging was defined in evaluation of 55 nonselected patients. The mean amplitude of cyclic variation of integrated backscatter in normal segments (long-axis view) was as follows: basal septum, 4.2 +/- 1.3 dB (mean +/- SD; n = 27), mid-septum, 4.5 +/- 1.0 dB (n = 26), basal posterior, 4.8 +/- 1.0 dB (n = 30), and mid-posterior, 4.8 +/- 1.2 decibels (n = 27). The respective mean delay values (R wave to nadir) were as follows: 0.89 +/- 0.09, 0.84 +/- 0.09, 0.86 +/- 0.09, and 0.85 +/- 0.12. At least one cardiac cycle could be analyzed fully in 62% of patients. Limitations included technically difficult two-dimensional echocardiography, inadequate M line orientation, technically remediable errors, or poor quality integrated backscatter images. In abnormal segments (n = 13) cyclic variation was reduced and delay was prolonged (1.2 +/- 1.1 dB and 1.21 +/- 1.1, respectively). Intraobserver and interobserver variability for amplitude measurements were modest, with respective correlation coefficients of r = 0.93; r = 0.72. The findings demonstrate that M-mode--assisted integrated backscatter is a practical approach for characterization of regional myocardial properties promptly and at the bedside in a large portion of patients with cardiac disease. PMID- 2206543 TI - Applications of cross-correlation techniques to the quantitation of wall motion in short-axis two-dimensional echocardiographic images. AB - Echocardiography is now a mainstay in the diagnosis of cardiovascular disease. Rapid methods for quantitation of the images would provide an effective tool for the diagnosis of change in left ventricular function. The purpose of this article is to show the feasibility of using the cross-correlation technique to quantify change in left ventricular function over time in two-dimensional short-axis echocardiographic images. Radial histograms of radial distance versus the number of probable specular targets are formed in eight sectors on each frame during the cardiac cycle. These histograms are then shifted to a position of best correlation. The number of radial bins through which the histograms at end systole are shifted to correlate with those of the frame at end diastole defines the regional motion. The methods are described and preliminary findings are presented. PMID- 2206544 TI - Variability of Doppler echocardiographic indexes of left ventricular filling in transplant recipients and in normal subjects. AB - This study examines the reproducibility and variability of pulsed wave Doppler versus continuous wave Doppler ultrasound indexes of left ventricular filling in cardiac allograft recipients and in normal subjects. The following indexes were studied: isovolumic relaxation time, pressure half-time, peak early mitral flow velocity, and peak mitral flow velocity after atrial systole. Intraobserver and interobserver variability were assessed by regression analysis. Individual components of variance (subject, reader, beat, day, and tracing) were estimated in a subset of five patients and five normal subjects, and estimated total variance defined for each group. Temporal (day-to-day) variability for 95% confidence was estimated for these patients and for normal subjects. Temporal variability in the group from which the subsets were drawn was measured from absolute and percent change in values on two occasions. Estimated and observed 95% confidence limits were compared. Intersubject variability was the largest component of variance in both transplant recipients and in normal subjects. For all indexes in transplant recipients (in the absence of rejection) and normal subjects, observed absolute mean differences (+/- 2 standard deviations) between values from recordings taken on two different days were larger than the 95% confidence limits estimated from the components of variance analysis. The observed 95% limits for transplant recipients versus normal subjects were as follows: isovolumic relaxation time, 20 msec versus 6 msec; pressure half-time, 16 msec versus 9 msec; peak early mitral flow velocity, 32 cm per second versus 17 cm per second; and peak mitral flow velocity after atrial systole, 28 cm per second versus 10 cm per second.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206545 TI - Left and right ventricular flows by Doppler echocardiography: serial measurements in patients with aortic regurgitation during exercise, cold pressor stimulation, and vasodilation. AB - To test the practicality of Doppler echocardiography to measure serial change, biventricular outputs were measured in 15 patients with aortic regurgitation during control periods and during interventions of bicycle exercise, cold pressor stimulation, and vasodilation. Biventricular stroke volumes were measured in 10 normal subjects for validation of methods and differed by 2.8%. Reading errors were 3.7%. Signal quality improved between the first and last observation (p less than 0.05). Velocity signals were corrected for intercept angles, which averaged 12 and 19 degrees for right heart flows and 31 and 32 degrees for the left side of the heart in all subjects. Negative correlations occurred between intercept angles and the chronologic order in which the patients were studied for left (p = 0.02) and right (p = 0.05) flows. Mean flow areas varied 9% in the left ventricle and 20% in the right ventricle. Total variability for measuring flow determined from control values was 11% to 13%. When twice the variability was used as the detectable level of change, only exercise provoked real increases in biventricular flows in the majority of patients. We conclude that serial measurements of flow by Doppler echocardiographic methods had to exceed 20% to 25% to achieve significant change. Measuring intercept angle, resolving flow area, and learning are variables that need greater emphasis. PMID- 2206546 TI - Flow patterns in dilated cardiomyopathy: a pulsed-wave and color flow Doppler study. AB - In 48 patients with dilated cardiomyopathy, pulsed-wave and color Doppler examination were performed. In addition, 14 normal patients served as control subjects. Peak inflow velocity at the level of the mitral valve, middle left ventricle, and apex and outflow velocity at the level of the apex, middle left ventricle, and subaortic area were measured. In normal patients there was brisk propagation of inflow velocity to the apex. Patients with dilated cardiomyopathy demonstrated delayed propagation and prolongation of the duration of inflow compared with control subjects (p less than 0.04). Continuous apical flow was visualized in 25% of dilated cardiomyopathies and in no normal patients. Apical velocities were significantly increased in cardiomyopathies with significant mitral regurgitation. Outflow velocities were decreased in dilated cardiomyopathy. In patients with dilated cardiomyopathy and apical dyskinesis, flow directed toward the base was measured in the middle left ventricle during isovolumic relaxation secondary to dyskinetic rebound. Patterns of abnormal flow in dilated cardiomyopathies are readily apparent by color M-mode and two dimensional color Doppler. PMID- 2206547 TI - Influence of Doppler sample volume location on the assessment of changes in mitral inflow velocity profiles. AB - Previous studies that have validated Doppler indexes of mitral inflow have used pulsed wave sample volume locations either at the level of the mitral valve anulus or at the tips of the mitral valve leaflets. Although significant differences between absolute values for peak velocities and velocity time integrals at these sample volume locations have previously been reported, no information exists that has compared changes in inflow profiles after an intervention to improve left ventricular filling. To address this question, 13 patients with severe pulmonary hypertension (mean pulmonary artery pressure, 50 +/- 13 mm Hg) caused by chronic thromboembolic disease were studied with use of Doppler echocardiography immediately before and after surgical reduction of pulmonary hypertension (pulmonary vascular resistance decreased from 916 +/- 413 to 233 +/- 89 dynes.sec.cm5). This clinical model has been shown to have abnormal mitral inflow velocity profiles that improve markedly after surgery. Doppler measures of early and late peak velocities were significantly lower both before and after surgery when sampling at the mitral anulus compared with the leaflet tips, although late filling parameters and the deceleration of early flow velocity tended to differ little. With surgery, the significant increase in peak early velocity and the ratio of early to late velocity was present regardless of the sample volume location (peak E at leaflet tips, 47.1 +/- 16.0 to 68.9 +/- 15.4 [p less than 0.001], and at anulus, 40.7 +/- 11.3 to 56.2 +/- 14.6 cm/sec [p less than 0.001]; peak E/A at leaflet tips, 0.95 +/- 0.4 to 1.55 +/- 0.9, and at anulus, 0.78 +/- 0.3 to 1.32 +/- 0.7 [both p less than 0.02]).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206548 TI - Do Doppler color flow algorithms for mapping disturbed flow make sense? AB - It has been suggested that a major advantage of Doppler color flow mapping is its ability to visualize areas of disturbed ("turbulent") flow, for example, in valvular stenosis or regurgitation and in shunts. To investigate how various color flow mapping instruments display disturbed flow information, color image processing was used to evaluate the most common velocity-variance color encoding algorithms of seven commercially available ultrasound machines. In six of seven machines, green was reportedly added by the variance display algorithms to map areas of disturbed flow. The amount of green intensity added to each pixel along the red and blue portions of the velocity reference color bar was calculated for each machine. In this study, velocities displayed on the reference color bar ranged from +/- 46 to +/- 64 cm/sec, depending on the Nyquist limit. Of note, changing the Nyquist limits depicted on the color reference bars did not change the distribution of the intensities of red, blue, or green within the contour of the reference map, but merely assigned different velocities to the pixels. Most color flow mapping algorithms in our study added increasing intensities of green to increasing positive (red) or negative (blue) velocities along their color reference bars. Most of these machines also added increasing green to red and blue color intensities horizontally across their reference bars as a marker of increased variance (spectral broadening). However, at any given velocity, marked variations were noted between different color flow mapping instruments in the amount of green added to their color velocity reference bars.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206550 TI - Two-dimensional echocardiographic features of double outlet left ventricle. AB - In a cyanotic newborn infant, the diagnosis of double outlet left ventricle was made from the two-dimensional echocardiographic examination. The diagnosis was later confirmed at cardiac catheterization and surgery. The parasternal and subcostal views were especially useful for identification of the origin of both great arteries from the morphologic left ventricle. A review of the medical literature since 1967 revealed 77 cases of double outlet left ventricle, most of which were diagnosed only at surgery or postmortem examination. The anatomic features demonstrated with two-dimensional echocardiography in this case are representative of the findings cited most often in the cases reported in the medical literature. PMID- 2206549 TI - Prevalence of aortic regurgitation by color flow Doppler in relation to aortic root size. AB - To determine whether there is a correlation between aortic root size and the prevalence of aortic regurgitation, we performed color flow Doppler echocardiographic studies on 1015 consecutive patients during a 3-month period. Patients were grouped according to their M-mode aortic root diameter as measured in the left parasternal position. The measured groups ranged from 2.0 to 4.5 cm, grouped at 0.1 cm intervals. As the aortic root size enlarged, the prevalence of aortic regurgitation increased linearly (p less than 0.001; correlation coefficient, r = 0.75). At an aortic root size in the "small normal" range of 2.0 to 2.4 cm, the prevalence of aortic regurgitation was 0% to 15%. In the "intermediate" and "top normal" ranges of 2.9 to 3.7 cm, the prevalence of aortic regurgitation increased linearly from 15% to 47%. With aortic root dilation, the prevalence of aortic root regurgitation was generally more than 50%. The severity of aortic regurgitation was semiquantified. Aortic root size was not a good indicator for the severity of aortic regurgitation. Patients with moderate and severe aortic regurgitation had variable aortic root sizes. Throughout the range of aortic root sizes, mild aortic regurgitation predominated. We conclude that aortic regurgitation is a common finding in patients with aortic roots that are dilated or are in the "top normal" size range, that the prevalence of aortic regurgitation increases linearly with aortic root size, and that aortic root size does not correlate with the severity of aortic regurgitation. PMID- 2206551 TI - Evolution of the continuity equation in the Doppler echocardiographic assessment of the severity of valvular aortic stenosis. AB - The use of Doppler techniques has greatly enhanced the noninvasive ultrasound technique for evaluation of valvular aortic stenosis. M-mode and two-dimensional echocardiography could not reliably distinguish patients with severe aortic stenosis from those with milder obstructions. The hemodynamic information offered by Doppler complemented echocardiographic imaging and provided an alternative modality for evaluation of patients with aortic stenosis. By application of the modified Bernoulli equation, the pressure gradient across the stenotic aortic valve could be estimated by Doppler echocardiography. Though helpful and widely used, the information provided by the pressure gradient across the valve about the severity of the obstruction was not complete. The assessment of valvular aortic stenosis therefore includes an estimation of the valve area by application of the continuity equation. This review examines the maturation of the continuity equation by Doppler techniques and discusses the implications of the procedure. PMID- 2206552 TI - The determination of aortic valve area by the Gorlin formula: what the cardiac sonographer should know. AB - The application of the Gorlin formula in the cardiac catheterization laboratory is the standard of reference for the determination of aortic valve area. The continuity equation now enables the cardiac sonographer to determine aortic valve area noninvasively in the echocardiography laboratory. The comparison of the results obtained by the two methods is inevitable. The cardiac sonographer should have a basic understanding of the theory and pitfalls of the Gorlin formula so that when conflicting results are obtained, the possible reasons why will be clear. PMID- 2206553 TI - The evaluation of the abdominal aorta: a "how-to" for cardiac sonographers. AB - A thorough evaluation of the abdominal aorta can be readily achieved by use of the standard views of the echocardiographic examination. The ultrasound evaluation of the abdominal aorta represents a logical extension of the standard echocardiographic examination of the adult patient. This article provides the information needed to carry out a complete ultrasound examination of the abdominal aorta including the anatomy, the vascular disease, and the steps involved in accomplishing the ultrasound examination of the abdominal aorta. PMID- 2206554 TI - Isolation of two new proteins from bovine colostrum which stimulate epidermal growth factor-dependent colony formation of NRK-49F cells. AB - Defatted bovine colostrum and decaseinated whey contain biological activity similar to that of TGF-beta in that they stimulate the anchorage-independent growth of NRK-49F cells in the presence of EGF. Two new proteins with such activity, termed BC-1 and BC-2, were isolated from decaseinated colostrum by a sequence of DEAE-Sephacel chromatography, Sephadex G-100 gel filtration in 1 M acetic acid, Sephadex G-50 re-gelfiltration in 8 M urea-1 M acetic acid and reverse-phase FPLCs. The two proteins showed distinctly different molecular weight from that of TGF-beta 1. BC-1 was a small Mr peptide of 8.5 kD. BC-2 had molecular mass of 46 kD, which yielded peptides of 46,40, and 6 kD on reduction. In contrast to TGF-beta, both proteins did not lose their biological activity on reduction. Both BC-1 and BC-2 suppress DNA synthesis in concanavalin A-stimulated thymocytes. These results suggest that BC-1 and BC-2 belong to a new class of mitogen/inhibitors, though their biological activities resemble those of TGF beta. PMID- 2206555 TI - High-level expression of TGF-beta 2 and the TGF-beta 2(414) precursor in Chinese hamster ovary cells. AB - Chinese hamster ovary (CHO) clones secreting high levels of transforming growth factor-beta 2 (TGF-beta 2) were obtained after transfection with a cDNA clone coding for the 414-amino acid TGF-beta 2 precursor and subsequent amplification with methotrexate. The TGF-beta 2 was secreted in a latent form since acidification was necessary for detection of maximal levels of bioactivity. Amino and carboxy-terminal sequencing of purified recombinant TGF-beta 2 indicated that correct processing of mature TGF-beta 2 had occurred. In addition to mature TGF-beta 2, the recombinant CHO clones secreted larger proteins having molecular weights of 85, 105, and 130 kD, which consisted of both mature and pro-region sequences when analyzed by immunoblotting using site-specific anti-peptide antibodies. Analysis of serum- and cell-free media from recombinant CHO cells metabolically labeled with [3H]glucosamine and [32P]orthophosphate indicated that pro-TGF-beta 2 was glycosylated and phosphorylated. Two-dimensional electrophoretic analysis of acid hydrolysates showed that the 32P was incorporated into mannose-6-phosphate. PMID- 2206556 TI - Cloning by polymerase chain reaction of a new mouse TGF-beta, mTGF-beta 3. AB - Two TGF-beta s, TGF-beta 1 and 2, have previously been isolated from the mouse. Here we report the isolation of a murine TGF-beta 3 cDNA. RNAs extracted from 15 day-old mouse embryos and several mouse cell lines were reverse-transcribed. These cDNA mixtures were used as substrates for polymerase chain-reaction amplifications, using oligonucleotides designed on the basis of known human and chicken TGF-beta 3 sequences, including the initiation and stop codons. Several overlapping cDNAs containing either the amino-terminal domain or the carboxy terminal domain, as well as the complete 1.2-kb coding region of the mouse TGF beta 3 cDNA were obtained. The mouse TGF-beta 3 coding region is 1230 nucleotides long and codes for a 410 amino acid polypeptide very similar to its human counterpart. This cDNA hybridizes to a unique 3.5-kb RNA and is differentially expressed in various mouse tissues and at different embryonic stages. PMID- 2206557 TI - Interactions of growth factors present in bone matrix with bone cells: effects on DNA synthesis and alkaline phosphatase. AB - It has been shown that bone cells produce and secrete several growth factors (GFs) which are also found in the bone matrix. To investigate the role of these growth factors in bone cell metabolism, we compared the effects of different factors separately and in combination with respect to osteoblastic cell proliferation and differentiation. While basic fibroblast GF (FGF), transforming GF beta-1 (TGF beta), and platelet-derived GF (PDGF) enhance DNA synthesis, they had the opposite effect on alkaline phosphatase (ALP) activity in cell extracts: FGF, TGF beta, and PDGF inhibited cell ALP but strongly stimulated DNA synthesis. The IGFs had little effect on cell ALP but increased the release of ALP into the conditioned medium. In mitogenic tests of combinations of GFs, most had at least additive effects at low concentrations, and FGF, TGF beta, and IGF2 produced synergistic effects. Evidence is presented for (1) the modulation of the effects of one GF by the action of other GF, (2) synergistic interactions between FGF, TGF beta, and IGF2, and (3) a possible role for the observed interactions among GF for the mitogenic effect of human bone extract. PMID- 2206558 TI - Inverse relationship between estrogen receptor and epidermal growth factor receptor mRNA levels in human breast cancer cell lines. AB - Epidermal growth factor receptors (EGF-R) are present in a number of human breast cancer cell lines and tumor biopsies. Furthermore, it has been suggested that EGF R levels are higher in estrogen receptor negative (ER-) than in ER+ human breast tumors and that EGF-R status may be a prognostic indicator in breast cancer. The present study was undertaken to establish whether there is a quantitative relationship between EGF-R and ER mRNA concentrations in a series of 10 well characterized human breast cancer cell lines. All cell lines expressed detectable quantities of EGF-R mRNA by Northern analysis but the relative abundance of EGF-R mRNA varied more than 50-fold. Two transcripts corresponding to the 10.5- and 5.8 kb mRNAs described in other cell types were present but in different relative proportions in different cell lines. When these lines were divided into an ER+ and an ER- group based on their ability to bind estradiol, ER- cell lines were shown to express significantly higher concentrations of EGF-R mRNA than did ER+ cell lines (p less than 0.005). Furthermore, linear-regression analysis revealed a significant inverse relationship between ER and EGF-R mRNA concentrations both within the group of 10 human breast cancer cell lines as a whole (r = 0.66) and within the 6 functionally ER + lines (r = 0.77). This demonstration of a significant (p less than 0.005) inverse relationship between the concentrations of ER and EGF-R mRNAs in ER + cell lines raises the possibility of reciprocal regulation of the expression of these genes in human breast cancer. PMID- 2206559 TI - Contractile and binding activities of structural analogues of LTC4 in the longitudinal muscle of guinea-pig ileum. AB - High affinity binding sites for LTC4 have been identified in various tissues, including guinea-pig ileal longitudinal muscle. More recently, it has been shown that LTC4 binds to non-receptor sites as well, particularly to glutathione transferases. In the present study, LTC4 and 9 chemically synthesized analogues, as well as the SRS-A antagonist FPL 55712 and S-decyl-glutathione, were tested for their ability to inhibit 3H-LTC4 binding in membranes from guinea-pig ileal longitudinal muscle and to affect the tone of the ileum in vitro. A significant correlation between binding and contractile activities was found for the LTC4 analogues and FPL 55712. However, S-decyl-glutathione, although possessing some affinity for LTC4 binding sites, was devoid of any effect on guinea-pig ileum tone at least up to 10(-5) M, thus indicating that these sites cannot be functional receptors, although they may represent other units involved in leukotriene action, e.g. uptake sites. PMID- 2206560 TI - Effects of the thromboxane A2 analogue, STA2, on the transmembrane potentials of guinea pig ventricular muscles under normal and simulated ischaemic conditions. AB - To assess whether thromboxane A2 (TXA2) exerts a direct electrophysiological effect on cardiac muscle, the effects of STA2 (10 micrograms/l), a stable TXA2 analogue, on the action potentials were examined in isolated guinea pig ventricular muscles using conventional microelectrode techniques. STA2 failed to induce any significant changes in the action potential characteristics in both normal Tyrode's solution and the hyperkalemic (K+ = 10.8 mM) solution. 15 min of superfusion with the "ischemic" solution, which consisted of hyperkalemia (K+ = 10.8 mM), hypoxia (pO2 less than 50 mmHg), acidosis (pH = 6.4) and substrate deprivation (glucose-free), progressively shortened the action potential duration and reduced the resting membrane potential, action potential amplitude and Vmax. STA2 did not affect the changes in the action potential during such "ischemic" superfusion. These results indicate that STA2 exerts no direct electrophysiological effects on both the normal and the "ischemic" myocardium. The arrhythmogenic effects of TXA2 observed in in vivo studies might reflect the ability of TXA2 to induce platelet aggregation and vasoconstriction resulting in an exacerbation of myocardial ischemia. PMID- 2206561 TI - Low-density lipoproteins stimulate internal free calcium and prostacyclin release in endothelial cells. AB - We have studied the effects of low density lipoproteins (LDL) on the intracellular free calcium concentration [( Ca2+]i, measured with the fluorescent probe indo-1) and PGI2 release (measured with radioimmunoassay of 6-keto PGF1 alpha) in cultured endothelial cells from bovine aorta. Cells transferred to serum-free medium developed an increasing responsiveness to native LDL in terms of increases in [Ca2+]i. After 6 h, native LDL (20-160 micrograms/ml) concentration-dependently evoked immediate, but transient, elevations of [Ca2+]i (from 90 +/- 10 nmol/l to 530 +/- 60 nmol/l at 160 micrograms/ml LDL) and enhanced release of PGI2 at 160 micrograms/ml. Increases in [Ca2+]i were found also in the absence of extracellular Ca2+ indicating that native LDL induces mobilization of Ca2+ from internal stores. LDL oxidized by incubation with Cu2+ had no immediate effects on [Ca2+]i when applied at a concentration of 80 micrograms/ml, whereas 160 micrograms/ml, in the presence of 1 mmol/l extracellular Ca2+, elicited increases in [Ca2+]i and PGI2 release. We conclude that the stimulating actions of low concentrations of native LDL on endothelial cells are likely to be mediated by membrane receptors expressed after removal of serum. PMID- 2206563 TI - The spontaneous regression of cancer. A review of cases from 1900 to 1987. AB - The literature on the spontaneous regression of cancer is reviewed from 1966 to 1987 to update reviews by Everson & Cole and by Boyd. These authors reviewed all cases of spontaneous regression from 1900 to 1965. We then report the entire series from 1900 to 1987. We also attempted to determine what attributions for spontaneous regressions have been reported. Although almost half of the authors failed to speculate or specify a possible cause for the spontaneous regression, the remainder postulated responsible factors such as immunological or endocrine, surgical, necrosis, infection, or operative trauma. The only unorthodox treatment to appear in the literature was the psychological. We conclude that the literature on the spontaneous regression of cancer is still unable to provide unambiguous accounts of the mechanisms operating to affect these regressions. PMID- 2206562 TI - Transformation of 15-hydroperoxide of eicosapentaenoic acid to lipoxins and trihydroxyeicosatetraenoic acids by 5-lipoxygenase partially purified from potato tubers. AB - Incubation of 15-hydroperoxide of 5,8,11,14,17-eicosapentaenoic acid (15-HPEPE) with 5-lipoxygenase enzyme, partially purified from potato tubers, resulted in the generation of 6 isomers of lipoxin A5. These compounds were identified by GC/MS analysis of their methyl ester and trimethylsilyl ether derivatives with C values: 23.3, 24.5, 24.6, 24.9, 25 and 25.2 respectively. The major products of the enzymatic reaction on 15-HPEPE are 5,15-DiHEPE and 13,14,15-trihydroxy eicosatetraenoic acid as identified by RP-HPLC and GC/MS analysis. There are also two new trihydroxyl compounds of eicosapentaenoic acid identified as 11,12,15 trihydroxy and 11,14,15-trihydroxy eicosatetraenoic acid respectively. The transformation of these two trihydroxyl compounds may be due to non-enzymatic rearrangement of 15-HPEPE. PMID- 2206564 TI - Radium treatment for hemangioma in early childhood. Reconstruction and dosimetry of treatments, 1920-1959. AB - Between 1920 and 1959, a total of 14,647 children younger than 18 months were treated at Radiumhemmet with ionizing radiation for skin hemangioma. Seventy-two percent of the children were treated with radium needles or tubes, which were put into glass capsules and then applied to the hemangioma. The absorbed doses to different organs have been measured in a tissue equivalent phantom, representing a 6-month-old child. For a standard treatment of 8 Gy to the hemangioma the mean absorbed doses to the brain, eye lens, parotid gland, thyroid, breast anlage and gonads from 28 different treatment areas were 0.03-0.2 Gy. The mean absorbed dose to the organs in younger (less than 2 months) and older (14-18 months) children were up to 50% higher (0.04-0.1 Gy) and 33% lower (0.02-0.06 Gy) respectively, than for a 6-month-old child. The uncertainty in organ absorbed doses for each patient depended mostly on the estimation of the distance between the applicator and the site. PMID- 2206565 TI - Tumors after radiotherapy for skin hemangioma in childhood. A case-control study. AB - A case-control study was conducted to investigate the possible association between absorbed dose and cancer risk in a cohort of 14,647 individuals (33% males and 67% females) less than 18 months old and irradiated for skin hemangioma between 1920 and 1959. The cases consisted of 56 breast cancers (in 55 patients), 14 thyroid cancers, 16 brain tumors and 8 tumors of bone and soft tissues. Four controls were matched to each case. They were matched for sex, age at treatment, treatment modality and treatment year. Absorbed doses were categorized in three exposure groups, less than 0.1 Gy, 0.1-0.4 Gy, and greater than or equal to 0.5 Gy, and odds ratios (OR) were estimated with the lowest exposure group as reference. A statistically significant positive dose-response relationship was found for thyroid cancer (OR: 1.0; 4.8; 4.3) and for tumors of bone and soft tissues (OR: 1.0; 1.6; 19.5). For breast cancer and brain tumors no significant dose-response relationship could be found. The median absorbed dose in the tumor sites among the cases of thyroid cancer, tumors of bone and soft tissues, breast cancer and brain tumors was 0.2 Gy, 0.3 Gy, 0.03 Gy and 0.04 Gy respectively. The dose was probably too low to detect any dose-response relationship for breast cancer and brain tumors. PMID- 2206567 TI - Risk of cervical cancer among wives of men with carcinoma of the penis. AB - The relationship between carcinomas of the penis and cervix uteri was analyzed in married couples. The final series comprised 239 patients with squamous cell carcinoma of the penis and their 224 wives. Two wives were found to have squamous cell carcinoma of the cervix uteri. The expected number of cervical cancers within the group of wives was 1.88, the relative risk thus being 1.05 (95% confidence interval 0.13-3.8). The incidence of condylomas has increased during the recent decades, while that of carcinomas of the penis and uterine cervix has decreased. The results of this study did not support the hypothesis that wives of men with penile cancer incur an increased risk of carcinoma of the cervix uteri. Although there is much evidence from a large number of studies that human papilloma virus (HPV) has a role in the aetiology of cervical cancer, our study suggests that HPV associated with genital malignancies has a low infectivity or that these cancers have multifactorial aetiology. PMID- 2206566 TI - Malignant disease after radiation treatment of benign gynaecological disorders. A study of a cohort of metropathia patients. AB - One hundred and seven cases of malignant tumours occurred among 788 women irradiated 1912 to 1977 for metropathia. One hundred and seventy-three women out of 1,219 referred for the same diagnosis and not irradiated developed a malignant tumour. The tumours were diagnosed between 1958 and 1982. The relative risk of malignant tumours among the irradiated women was 1.22 and among the non irradiated 1.09 compared to cancer registry data. A statistically non-significant increase of the relative risk was found in the irradiated patients for tumours of the rectum (1.58), colon (1.46), and the nervous system (1.67). A decreased overall relative risk was seen for cancer of the breast (0.92) after irradiation, but women treated at the age of 50 or more had an increased risk (2.08). The relative cancer risk of the heavily irradiated sites was not increased during the first 20 years after irradiation, but a statistically significant increase of the risk was seen after 30 years. PMID- 2206568 TI - The excess mortality rate. A useful concept in cancer epidemiology. AB - Death cause registers and cancer incidence registers are often used to elucidate progress (or lack of progress) in the battle against cancer. Trends in the age adjusted mortality rate of cancer or of specific cancer types may thus mirror the overall effect of anticancer interventions (prevention, early diagnostics, treatment), but are often influenced by changes in the death cause diagnostics or in the coding routines at the registers. Relative survival rate (or its inversion, relative mortality rate) is sometimes used in order to elucidate improvement due to treatment. It is independent of the death cause diagnoses but often seriously influenced by changes in diagnostics of incident cancer; earlier diagnosis and increased detection of non-fatal cases may thus give an improved relative survival rate, quite unrelated to any improvement in the treatment. In the present paper the excess mortality rate is introduced as a measure which can give additional information concerning effects of anticancer interventions. In contrast to age-adjusted mortality rate it is not dependent on death cause diagnoses or coding routines, and in contrast to relative survival it is independent of the rate of non-fatal incident cancer cases. PMID- 2206569 TI - Hypercalcaemia in patients with disseminated breast cancer. AB - Ninety-three patients with breast cancer and elevated serum calcium (Ca) had a median survival of 8.5 months from the diagnosis of hypercalcaemia. The presence of symptoms, visceral disease and level of serum Ca were independent prognostic indicators for survival on multivariate analysis. Patients without symptoms, no evidence of visceral disease and Ca less than or equal to 3.0 mmol/l had the best prognosis (median survival 3.5 years) when compared to patients with one adverse prognostic feature (median survival 16 months); two or more unfavourable features identified the worst prognostic category (median survival 2.5 months). Future studies of hypercalcaemia in malignancy should assess the influence of treatment on survival as well as symptom control and should take into account disease related prognostic factors in addition to the level of serum calcium. PMID- 2206570 TI - Interleukin-2 receptor levels in non-Hodgkin's lymphoma. Correlation to histological degree of malignancy and presence of constitutional symptoms. AB - Serum interleukin-2 receptor (Il-2R) levels were measured in 28 untreated patients with stage III or IV non-Hodgkin's lymphoma (low grade lymphoma: n = 11, high grade lymphoma: n = 17). Markedly higher levels of Il-2R were found in these patients compared to an age- and sex-matched control group. Significant differences were also found between the high grade group and the low grade group, and between patients with and without constitutional (B) symptoms. It has previously been shown that Il-2R levels vary according to tumor burden in patients with non-Hodgkin's lymphoma. Our data indicate that histological degree of malignancy as well as presence or absence of B symptoms may also influence Il 2R levels in these patients. All three parameters should therefore be taken into account when the clinical significance of Il-2R levels is evaluated. PMID- 2206571 TI - Cisplatin and tegafur in recurrent head and neck cancer. A phase II study. AB - A phase II study of cisplatin and tegafur in recurrent epidermoid head and neck cancer is presented. All patients were treated with cisplatin 100 mg/m2 every 4 weeks. Twenty-nine received tegafur 750 mg/m2 days 2-28 orally and 18 patients, who were unable to take tegafur orally, were treated with tegafur 1,500 mg/m2 intravenously days 2-5. The response rate in the oral group was 28.5% and the median survival 29 weeks. The response rate in the intravenous group was 6% and the median survival was 17 weeks. We conclude that cisplatin and oral tegafur is active against head and neck cancer. PMID- 2206572 TI - The natural course of emesis after carboplatin treatment. AB - Twenty-eight patients receiving their first cycle of carboplatin treatment (300 400 mg/m2) entered a prospective study in which the natural course and intensity of postchemotherapy emesis was evaluated. Twenty-five patients (89%) experienced nausea at some time after carboplatin treatment and twenty-three patients (82%) vomited. The median number of emetic episodes was 13.5. In the 23 patients who experienced vomiting, the mean period of latency of vomiting (time from start of carboplatin administration to onset of vomiting) was 6.25 h. The period of maximum incidence of vomiting was between 8 and 12 h (71% of patients with vomiting). Between 6 and 14 h after the start of carboplatin treatment, more than 50% of patients were continuously vomiting. Vomiting declined significantly after 24 h. According to these data, carboplatin is a severely emetic drug. Prospective antiemetic trials are necessary in order to obtain antiemetic schedules which are able to increase the tolerance to carboplatin treatment. PMID- 2206573 TI - Incidence of hypothyroidism after irradiation of the neck with special reference to lymphoma patients. A retrospective and prospective analysis. AB - Twenty-eight patients were studied prospectively in order to determine the incidence of hypothyroidism after mantle irradiation for malignant lymphoma. This group was compared with a historical group of 65 patients, among them 36 patients with malignant lymphoma. The mean follow-up was 30 months for the prospective group and 46 months for the retrospective group. The mean thyroid dose for irradiated malignant lymphomas in the prospective and the retrospective group was 45 Gy and 43 Gy respectively. For other tumors with neck irradiation (retrospective group) the mean thyroid dose was 53 Gy. There were no cases of clinical hypothyroidism in our study. As for subclinical hypothyroidism which is characterised by elevated TSH, the incidence was 22% in the prospective group and 3% in the retrospective group, i.e. 8/93 patients showed a hypothyroid dysfunction. Three of the 8 patients with subclinical hypothyroidism had undergone lymphangiography before radiotherapy. Due to the elevated iodine pool a lymphangiogram is considered as a risk factor for hypothyroidism as well as for hyperthyroidism, which we observed twice in the prospective group. Evaluation of the thyroid function before lymphangiography and irradiation as well as regular thyroid function studies during the follow-up are recommended in order to detect hypothyroidism in time. PMID- 2206574 TI - Cancer of the supraglottic larynx with neck node metastasis treated by radiation therapy only. The revised 1987 UICC classification system as prognostic indicator. AB - In 1987, a thoroughly renewed TNM classification was published; the revision was a conjunct effort of the International Union Against Cancer (UICC) and American Joint Committee on Cancer (AJCC). With respect to the former UICC classification, a major change was introduced regarding the regional lymph node subcategories in head and neck cancer; that is compared to the 1978 edition the subjective subcategory of fixation was eliminated and size of the lymph node has become of paramount importance. To see whether the 1987 UICC classification system is indeed more predictive and discriminatory than the 1978 edition, we have analysed patients with supraglottic cancer with clinically detectable lymph node metastasis (T1-4, N+). All patients treated between 1965 and 1980 by radiation therapy only were staged according to both editions of the UICC classification system. From these data we conclude that the prognosis of patients with lymph nodal involvement indeed worsens from N1 to N3 when classified according to the 1987 edition; in contrast, no difference is seen between the N1, N2 or N3 subcategories when staged according to the 1978 classification rules. PMID- 2206575 TI - Carcinoma of the nasopharynx. A retrospective analysis of treatment results in 125 patients. AB - From 1958 to 1982, 125 patients with histologically verified carcinoma of the nasopharynx were treated with external radiotherapy as the sole curative intent. The 5-year actuarial survival rates by stage were as follows: stage I 68%, stage II 64%, stage III 44%, and stage IV 20%. Primary control rate by T-category was 71% in T1, 67% in T2, 52% in T3, and 64% in T4. Regional control rate was 96% in N0, 76% in N1, 61% in N2, and 63% in N3. The T-category was found to be an important prognostic parameter for survival. PMID- 2206576 TI - Immune competence in 90Sr-exposed, adult thymectomized and antilymphocyteglobulin treated CBA mice. II. Reticuloendothelial phagocytic function and in vitro mitogen responsiveness of spleen cells. AB - The hypothesis that immune system failure plays a role in the development of radiation induced tumours was recently investigated experimentally. Young adult CBA mice, intact or immunocompromised by adult thymectomy (ATx) and/or anti lymphocyteglobulin (ALG) treatment, were exposed to single doses of 90Sr, after which tumour development was monitored. To evaluate the experimental results required knowledge about the immunological responsiveness of the mice. The present paper contributes to that knowledge by reporting on the in vitro responsiveness of lymphoid cells to mitogens (LPS, PHA, Con-A) and the in vivo phagocytic functioning of the reticuloendothelial system (RES), measured as the rate of clearance of 125I-albumin micro-aggregates in peripheral blood. 90Sr, ATx and ALG-treatments, separately and in combination, suppressed mitogenic lymphoid cell activation, whereas the RES phagocytic function remained unchanged, except in response to 90Sr + ALG treatment, which seemed to slightly inhibit phagocytic activity. PMID- 2206577 TI - Enhancement of radiation sensitivity in iododeoxyuridine labelled cells exposed to low energy x-rays. AB - In order to investigate if low-energy x-rays induce Auger cascades by photoelectric absorption in iodine present in DNA, CHO cells were labelled with iododeoxyuridine (IUdR) for 72 hours. Following labelling, the cells were either irradiated with low-energy x-rays (75 kV, 4 mm Al) or 137Cs-gamma-rays. The radiation response was measured using clonogenic survival, and the survival parameters were analyzed according to the linear quadratic model. The dose modifying factors were determined as the ratios of the alpha-coefficients. The IUdR labelled cells were found to be about 3.2 times as sensitive as the control cells when irradiated with low-energy x-rays. For 137Cs-gamma the ratio was about 1.5. The standard deviations were estimated by Gauss' approximation to be about 0.5 for both irradiation conditions. PMID- 2206578 TI - Calculation and measurements of absorbed dose in total body irradiation. AB - A method which is simple, reliable, and rapid to use in clinical routine for basic dose calculation in total body irradiation (TBI) has been tested with 8 MV x-rays. The dosimetry follows, as far as possible, national and international recommendations for conventional radiotherapy. The dose rate at different locations and depths is calculated from the absorbed dose rate at dose maximum for a phantom size of 30 x 30 x 30 cm in the TBI field (Dc), an inverse square law factor (SAD2/SPD2), the tissue-maximum ratio (TMR), an equivalent phantom and patient size correction factor (A), a factor for lack of back-scattering material (B), an off-axis output correction factor (O), and a factor that corrects for off axis variations in effective photon beam energy and for oblique beam penetration of the patient (R). The collimator opening is constant for all patient sizes. It is shown that TMR, A, B and R can be measured in conventional geometry in ordinary phantoms but at an extended distance, while Dc, O and SAD2/SPD2 must be measured in TBI geometry. Tests in Humanoid phantoms showed an agreement in measured and planned AP/2 doses of 2% or better. If the calculation method is used for lower photon energies or in other TBI geometries it may be necessary to correct for the elliptical shape of the patient and for back-scattered radiation from the walls or floor. PMID- 2206579 TI - Aclarubicin in the treatment of advanced gastrointestinal adenocarcinoma. PMID- 2206580 TI - Treatment of early vocal cord carcinoma with 60Co gamma rays, 8/10 MV x-rays, or 4 MV x-rays--are the results different? PMID- 2206581 TI - Second cancer following chemotherapy and radiotherapy. An epidemiological perspective. AB - Both ionizing radiation and alkylating chemicals are used to treat cancer, and both are themselves carcinogenic. Epidemiological methods of study have provided a substantial amount of information on the long-term risks of the two types of treatment. Radiotherapy appears to increase the risk of a wide range of cancers, but the size of the increase is not substantial. Chemotherapy, in contrast, produces a very large increase in the risk of acute leukaemia, and does not generally appear to produce other types of cancer. Leukaemias following both treatment modalities appear rapidly, while the risk of solid tumours induced by radiotherapy is not manifested until a decade or more has elapsed. There does not seem to be synergy between the two types of therapy in their carcinogenic action. Continued use of the epidemiological approach is essential in risk-benefit evaluation of cancer therapy. PMID- 2206583 TI - Prostatic cancer. An overview. AB - Reliable study results are scarce in prostate cancer for several reasons. The treated tumors represent a wide variety of natural history and therapeutic response. One assumes to select 'soft' or minimally toxic treatment for patients with good prognostic factors while aggressive treatment is reserved for infaust prognosis. Stage, grade and prognostic factors may influence the indication and choice of treatment. Better treatment selection will depend on the outcome of actual ongoing randomized trials, the development of new drugs or existing drugs in new indications and, above all, basic studies on the growth potential and invasiveness of the prostate cancer cell. Defining the correct treatment for the right cancer in the right patient is our clinical challenge for the next decade. PMID- 2206582 TI - Cancer chemoprevention. A review of ongoing clinical studies. AB - The mass of experimental data on various possibilities of inhibiting the carcinogenic process is growing rapidly. However, the biological complexity of carcinogenesis and the intrinsic limitations of the animal models make it often very difficult to identify the real potentially effective agents among the hundreds currently being proposed. In fact, more than 600 potentially chemopreventive agents have been identified and approximately 30 of them are presently being tested in humans. The great heterogeneity of these compounds (they belong to over 20 different classes of chemicals) might be a positive feature as it indicates that a variety of approaches is possible and that the options for selecting effective compounds will be numerous. In recent years, what could be called 'clinical chemoprevention' (that is controlled studies to evaluate in human subjects the efficacy of potentially chemopreventive agents) has developed considerably: according to American estimates 4 chemopreventive agents were tested clinically in 1981, 10 in 1985 and 18 in 1988. The number of reported preclinical investigations was 10 in 1985 and 75 in 1988. This rapid expansion has obviously led to some confusion in terminology and in the evaluation of primary results; at present there is still a need for further investigations to better define clinical chemoprevention and to differentiate it from chemotherapy. PMID- 2206584 TI - [40 years of the Portuguese Cardiology Society]. PMID- 2206586 TI - [Portuguese cardiology: what is its current situation?]. PMID- 2206585 TI - [The development of cardiology in the last 40 years]. AB - In order to correctly appreciate the way cardiology developed in the last 40 years, the "state-of-the-art" balance when the first World Congress took place, September-1950, in Paris, is made. The most current diagnostic methods were relatively scarce at the time-ECG, chest X ray, phonocardiography, pulse wave tracings, coupled with vectorcardiography and ballistocardiography, but in the well equipped hospitals right ventricular catheterization was already performed. The therapeutics of the important morbid situations-like congestive heart failure, arterial hypertension, myocardial infarction and ischemia was disappointing, but closed heart surgery was already taking place. Since then, things had changed suddenly. Over the last 40 years a marked scientific and technology explosion has emerged, that had benefited cardiology science, encompassing several broad areas, namely, patient approaching, pathophysiology understanding, the emergence of new drugs and clinical use, interventional cardiology and remarkable progress in open heart surgery. Imaging techniques development and other technology lead to a simple and accurate cardiac diagnosis. 24 hours ECG and blood pressure recording, and cardiac output measurement, greatly improves our medical knowledge. Computers development, representing the most significant technology advances, has given to cardiology non-predicted advances.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206587 TI - [The importance of heart disease in the various types of cerebral vascular disease. A prospective study]. AB - A prospective study was performed in 106 patients with acute stroke. The main purpose was the cardiac evaluation in the different types of cerebrovascular disease: Intracerebral hemorrhage (H), Cortical ischaemic events (C) and Subcortical ischaemic events (SC) and also to evaluate the interest of echocardiography in detecting occult cardiac sources of emboli. The study population included 54 men and 52 women with a mean age of 66.8 +/- 10.3 years. A thorough neurologic and cardiologic study with a computed tomography of the brain (TAC) and an echocardiogram (ECO) were performed in all patients. It was found 24 (23%) of H, 40 (38%) of C and 32 (30%) of SC. In the past history, heart diseases were more prevalent in C (p less than 0.04); previous stroke and systemic hypertension (HTA) were less prevalent in H (p less than 0.008) and in C (p less than 0.004), respectively. Atrial fibrillation (FA) was more frequent in ischaemic stroke (p less than 0.02) and within these in C (p less than 0.005). No more clinical and functional cardiac features or echocardiographic aspects had any difference in their prevalence in different types of stroke. Without clinical heart disease there were 19 (18%) cases but only in 10 were found in their echocardiograms a potentially embolic heart disease (PEHD) but 8 of them had questionable pathologic significance. IN CONCLUSION: C had more heart disease in their past history; FA is more frequent in C; it is difficult to diagnose a cerebral embolism with only a coexistent C and CPE, but if there is FA or a past history of heart disease in a C, the diagnosis of cerebral embolism is more probable; finally, echocardiography is of limited value to diagnose a PEHD in the elderly, however it makes possible to better evaluate most cardiac situations. PMID- 2206588 TI - [Changes in the coronary arteries in Kawasaki disease: echocardiographic aspects]. AB - OBJECTIVE: Evaluation of coronary anomalies in children with Kawasaki disease (KD) by two-dimensional echocardiography. SETTING: Outpatient and Laboratory of Echocardiography in the Pediatric Cardiology Department of Santa Marta Hospital. PATIENTS: Forty four children (M/F = 1.7/1) with a mean age of 2 years and 8 months (range from 2 months to 8 years) underwent Outpatient and serial echocardiographic study from July 1984 to December 1988. RESULTS: Coronary artery anomalies were demonstrated in 13 (52%) of 44 children; 11 (25%) had uniform dilatation and 12 (27%) had aneurysms. These anomalies were never observed before the first week of illness. During a mean follow-up of 8.4 months, we have observed normalization of coronary arteries lumen, in 10 (43.4%) of the 23 cases. The anomalies remained in 13 (56.6%). CONCLUSIONS: Coronary artery anomalies are a frequent complication of KD. In about 50% of patients, coronary artery anomalies remained in a mean follow-up of 8 months. Two-dimensional echocardiography is a good method to study coronary anomalies in KD. PMID- 2206589 TI - [The effectiveness of amiodarone seems to depend highly on the pathology underlying the arrhythmia]. AB - STUDY OBJECTIVE: To evaluate the efficacy of amiodarone in tachyarrhythmias occurring acutely, in patients with different nosological entities of the heart. DESIGN: A retrospective study. SETTING: Emergency-room patients and ward patients, in an Internal Medicine Department of a University Hospital. PATIENTS: Sequential sample of 148 patients with acute tachyarrhythmias, 138 out of them supraventricular (atrial fibrillation--116 cases; paraoxysmal supraventricular tachycardia--14 cases, and atrial flutter--8 cases). INTERVENTIONS: 81 patients had been treated with amiodarone; 67 patients had received several other antiarrhythmic drugs. MEASUREMENTS AND MAIN RESULTS: A favourable result of antiarrhythmic treatment was achieved in 84% of the patients who received amiodarone and in only 57% of those having been treated with the other antiarrhythmic drugs (p less than 0.025). A clearly distinct benefit of amiodorone was seen in the subgroup of patients with mitral stenosis, when compared with the whole of the other treatments (p less than 0.001). Amiodarone results were also better than the other antiarrhythmic ones in hypertensive patients (p less than 0.05). There was no difference between amiodarone and the remaining compounds in patients suffering from ischaemic heart disease, congestive heart failure and chronic obstructive lung disease. No adverse side effects were verified is this short term treated sequence of patients. CONCLUSIONS: Amiodarone seems, in this study, to be a very effective antiarrhythmic drug for the treatment of supraventricular tachyarrhythmias. Its efficacy was superior in cases where the underlying disease was mitral stenosis or arterial hypertension. So, effectiveness of the compound seems to depend on the nature of the subjacente cardiac disease. The short term tolerability has been excellent. However, the small number of patients studied claims for bigger scaled similar investigations. PMID- 2206590 TI - [Hypertrophic non-obstructive cardiomyopathy associated with interauricular communication. Report of a case]. AB - It is unusual the association between hypertrophic cardiomyopathy and atrial septal defect. We present in this paper the results of the tests done to one patient with these two diseases and profit to make an update of the bibliography on this subject. PMID- 2206591 TI - Probability of cardiac disease: Framingham revisited. AB - A study was undertaken to test the utility of a strict Bayesian formulation for the diagnosis of coronary disease. Using known probabilities of the disease for men and women in four different age groups and by estimating the probabilities of disease in patients with four important risk factors, we were able to estimate the probability of coronary disease in 512 different subsets of patients. We found that it was not possible to rigourously apply Bayes formula because neither the probability of the risk factor given the disease nor in patients without disease was obtainable in the medical literature. We conclude that to use Bayes formula without equivocation in coronary diagnosis does not appear possible in the present state of statistical knowledge. Rather, an expert system in the form of a knowledge-base would appear to be more achievable. PMID- 2206592 TI - [Coronary angioplasty in acute coronary syndrome]. AB - PTCA is a widely used technique in patients post-acute myocardial infarction (AMI) as well as in unstable angina (UA). The precise timing of its application and some aspects of the indication nowadays remains a matter of controversy. Primary PTCA is not generally considered to be the initial treatment of AMI. In contrast, immediate PTCA after thrombolysis has been proposed attempting to decrease the incidence of early reocclusion, improve myocardial salvage, decrease the incidence of postinfarction angina and improve survival. Nevertheless, three recent controlled studies (TAMI, TIMI II and ECSG) have demonstrated that an "aggressive" strategy with obligatory, invasive intervention following thrombolysis does not provide any advantage in terms of survival, rate of reocclusion or improved ventricular function and is, in fact, likely to be harmful. Emergent coronary arteriography after AMI should be reserved for unstable patients with continued or recurrent ischemia in the CCU. In elective basis it should be indicated in all patients with spontaneous or provocable ischemia prior to hospital discharge. If high grade coronary stenoses are identified, the patient should be considered for PTCA or surgical revascularization. In our own experience with coronary arteriography 24 hours to 15 days after intravenous thrombolysis with SK, PTCA is anatomically feasible in 44% of all the patients and in 60% of those showing a patent vessel. However, when indicated because of postinfarction angina or a positive stress test, PTCA was performed only in 22%, some of them presenting with a totally occluded vessel. In case of stenosis lesser than 100% the dilation success rate is slightly lower than that of out entire series (84% vs 88%), but the incidence of acute occlusion is significantly higher (10% vs 6%), particularly in patients with angiographic evidence of intracoronary thrombi. The incidence of "non significant" (less than 70%) stenosis spontaneously increases when the coronary arteriography is performed late during hospitalization (34% vs 17% when the patient is studied in the first 24-48 hours).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206593 TI - Sudden death in ischemic heart disease. AB - Sudden death, defined as the death that occurs naturally, unexpectedly and instantaneously or within the first hour of the onset of premonitory symptoms, is one of the most important challenge of the modern cardiology. This is due to both, its elevated incidence (400,000 to 500,000 cases per year in United States alone) and its dramatic presentation (many of the victims are relatively young and have an acceptable quality of life). We have studied de Holter tapes of 233 patients who died suddenly and we can demonstrate that 80% of cases were due to ventricular tachyarrhythmias (ventricular fibrillation 60% and torsades de pointes 20%) and the rameinens 20% were due to bradyarrhythmias. It is well known that ischemic heart disease is the leading cause of sudden death, being responsible for more than 80% of cases. In the present article we will analyze the relationship between sudden death and the different types of ischemic heart disease: stable angina pectoris, unstable angina pectoris, acute myocardial infarction and postinfarction and silent myocardial ischemia. PMID- 2206594 TI - Magnetic resonance imaging of joints. PMID- 2206595 TI - Magnetic resonance imaging of the shoulder. PMID- 2206596 TI - Magnetic resonance imaging of the wrist. PMID- 2206597 TI - Magnetic resonance imaging of hip disorders. PMID- 2206598 TI - Magnetic resonance imaging of the knee. PMID- 2206599 TI - Magnetic resonance imaging of the temporomandibular joint. PMID- 2206600 TI - Application of long synthetic oligonucleotides for gene analysis: effect of probe length and stringency conditions on hybridization specificity. AB - Two different lengths of long unique synthetic oligonucleotide probes (37- and 48 mers) specific for human major histocompatibility complex (MHC) class II beta genes were synthesized. These oligonucleotides were utilized to examine factors influencing hybridization specificity. Both probe length and stringency of washing conditions were found to be crucial factors for sequence-specific hybridization. PMID- 2206601 TI - Hybrid selection of mRNA with biotinylated DNA. AB - A novel, convenient, and highly efficient hybrid selection procedure is described. The method utilizes the polymerase chain reaction (PCR) in which one of two primers is biotinylated at the 5'-terminus. The concentration of the biotinylated primer is 100 times that of the other to synthesize biotinylated single-stranded DNA (asymmetric PCR). After hybridization of the biotinylated DNA with mRNA in solution, streptavidin agarose is used to trap the hybrid duplex of mRNA.DNA-biotin onto the solid matrix. The selected mRNA is then eluted from the streptavidin agarose. The quantitative physical recovery of selected mRNA is about 70% with about 33% retention of biological activity. PMID- 2206602 TI - An improved strategy for generating a family of unidirectional deletions on large DNA fragments. AB - A modification of the Barnes "kilo-sequencing" method is described. The procedure presented here makes it possible to obtain a series of nested deletions on large DNA fragments in only two days. It applies to double-stranded DNA, and thus can be used with plasmids as well as the M13mp series of bacteriophages. The main improvements are the use of a second restriction enzyme, which makes it possible to begin the deletions at any site on the DNA fragment, and the use of mung bean nuclease for trimming the DNA edges so that any restriction enzyme can be used. This method, using a pUC vector and sequencing on double-stranded DNA, would make it possible to read a DNA nucleotide sequence on both strands starting with only one construction. PMID- 2206603 TI - [Oral habits in small children]. AB - The correction of oral stereotypes when children still have their milk teeth is known to be a rewarding measure in the prophylaxis of dental anomalies. Based on clinical examples, questions concerning the methodology and necessity of mechanical intervention are discussed along with favourable times for such action. The casuistic discussion supports the following conclusions: 1. Oral stereotypes that remain persistent beyond the third year do not necessarily lead to dentition deformities. 2. The favourable moment to offer small children aid in getting rid of their habit is not necessarily a matter of chronological or dental age, but depends rather more on the phase of personality development the child is going through at the time. PMID- 2206604 TI - [In-vitro plaque accumulation on different filling materials]. AB - The influence of the surface roughness of dental filling materials as well as of specific properties of materials on plaque accumulation was to be tested in a comparative study for various materials (Degulor S, Amalcap SAS, Visio Dispers, Ketak-Fil, CuproDur, Harvard Cement) was to be tested in a comparative investigation. For this purpose, the different materials were placed in a Streptococcus mutans NCTC 10449 culture medium containing sucrose, and incubated for three days at 37 degree C. Following this, the specific accumulation of polysaccharides formed outside of cells (plaque) was subjected to gravimetric analysis. Filling materials that take a high polish (Degulor S, Amalcap SAS, Visio Dispers) accumulated only 25 to 50% as much plaque as did cements. Within the group of cements there were also differences (up to 40%) in spite of similar surface roughness. These differences are presumably due to properties specific to the materials. In preliminary examinations of the products named, antibacterial effects were registered in three cases (Degulor S, Harvard Cement and Cupro-Dur- inhibiting areola between 1 and 7.5 mm). PMID- 2206605 TI - [Determination of caries risk in federal soldiers]. AB - Using Dentocult/Dentobuff the "caries risk" was determined in 102 adult test persons three times within a period of 44 weeks and correlated with clinical and radiological study results (Spearman rank correlation, multiple calculation of correlation and regression). The patients were given dental treatment as required during the study period. A close correlation was seen between the individual Dentocult measurements taken at different times, which speaks for relative constancy in these measured values in individual test persons. No significant correlation with the overall increase in caries was found and did not become apparent until cases of caries were categorised as primary, secondary and smooth surface types. The correlation coefficient was, however, low at R = 0.2-0.4. The prognostic value of the Dentocult/Dentobuff system was at best about 50%. A connection between the caries risk test and clinical parameters became evident in the presence of localised retention. On the whole, however, it must be said that our studies do not show that this method makes it possible to prognosticate the caries risk in individual patients. PMID- 2206606 TI - [Salt fluoridation]. AB - The author reports on more than 17 years of trials involving determination of optimum daily requirement of F-, water and salt as well as the F- content of various foods and of urine. On the basis of these physiological data, support is found for salt fluoridation to prevent tooth decay. The results demonstrate that salt fluoridation is not only suitable for community use in automated systems, but is also a universally applicable substance. PMID- 2206607 TI - [Demonstration of Streptococcus sobrinus in human oral cavity]. AB - From 133 saliva samples of humans we isolated 32 strains (24%) of Streptococcus sobrinus on an BYCSB selective medium. The very hard colonies of S. sobrinus on this medium were characterized by a distinct chalky white halo of water insoluble glucan ("glucan-halo") produced in large amounts from the sucrose by extracellular glucosyltransferase which has diffused out into the isolation medium. All of the isolated S. sobrinus strains fermented ordinarily mannitol and sorbitol, but not raffinose and melibiose. The occurrence of this special subspecies within the S. mutans-group may play a more important role in the etiology of dental caries of caries-active persons in the future. PMID- 2206608 TI - [Moving nutrition to adaptation to caries control from viewpoint of behavioral research]. PMID- 2206609 TI - The autopsy: a dying art? A paediatric perspective. PMID- 2206610 TI - Contemporary issues in the use of growth hormone. PMID- 2206611 TI - Cystic fibrosis: an inborn error of cellular electrolyte transport? AB - Abnormal epithelial transport in cystic fibrosis (CF) appears to provide a unifying hypothesis to explain the varying clinical manifestations of CF. The major abnormality is the cell regulation of epithelial Cl- secretion; however, a number of other abnormalities of electrolyte transport has been observed. A description of the normal physiology of secretion and the current state of our knowledge of the abnormalities of epithelial secretion is discussed. PMID- 2206612 TI - Growth patterns, health and illness in preschool children from a multi-ethnic, poor socio-economic status municipality of Melbourne. AB - There are little longitudinal data available for sample populations of Australian children. Previous findings from the Brunswick Family Study, unlike earlier overseas studies, have shown that adverse family and social factors were not associated with growth abnormalities. Follow-up of 224 children from the cohort at 4 years of age has confirmed absence of significant growth disturbances, no mortality between 1 and 4 years, and serious morbidity due to organic illness in only 4% of the sample. However, 22% of the 4 year olds were found to have behaviour disturbances. These findings from a multi-ethnic, poorer socio-economic status population sample illustrate the importance of behaviour disturbances as one aspect of the new morbidity in Australian paediatrics and indicate that the once prevalent growth failure and organic morbidity consequent to family and social disadvantage have all but disappeared. PMID- 2206613 TI - Diagnosis and treatment of antenatal uropathies. AB - Thirty-five patients with significant fetal hydronephrosis detected on antenatal ultrasound had postnatal investigations which included ultrasound, 99mtechnetium diethylenetriamine pentacetic acid (99mTcDTPA) renal scans and micturating cystourethrograms. Antenatal and postnatal ultrasound were unable to determine reliably the level of obstruction causing the hydronephrosis. The 99mTcDTPA renal scan was useful in determining the necessity and timing of surgery, but could not exclude vesico-ureteric reflux. Seven patients required surgery in the neonatal period and a further seven children had surgery because of deterioration of the scan appearance on follow-up studies performed at 3, 6 and 12 months of age and then at longer time intervals. Twenty patients (almost 60%) have been managed conservatively for a mean of 28 months (range: 12 months-7 years) with no deterioration in renal function. PMID- 2206614 TI - Juxta-epiphyseal pathological fracture of the proximal femur secondary to metaphyseal chondrodysplasia. PMID- 2206615 TI - False negative results on newborn screening for cystic fibrosis. AB - Over a 5 year period in Newcastle, 18 new cases of cystic fibrosis (CF) were diagnosed in children who had been screened in the newborn period. In six of these children, the screening programme failed. Four of these children had a normal screen and an additional two had elevated immunoreactive trypsin (IRT), but there were problems with the notification procedure. Three of the children missed by the screening process had a significantly delayed diagnosis; in all three cases the diagnosis of CF was suspected clinically, but a sweat test was delayed because of false reassurance from the fact that the child had been screened for CF. In a fourth case, multiple elevated sweat electrolyte levels were obtained, but the diagnosis of CF was considered to be in doubt because of the normal IRT assay. A sweat test should be performed on any child in whom there is clinical suspicion of CF. PMID- 2206617 TI - Incidence of ABO haemolytic disease of the newborn in a group of Hong Kong babies with severe neonatal jaundice. AB - Two methods were used to determine the incidence of ABO haemolytic disease of the newborn (ABO-HDN) among Hong Kong Chinese infants. The first method employed the Lui elution technique to elute anti-A,B from cord blood of Group A and B babies with a Group O mother, and set out to correlate the titration score of the eluate with the serum bilirubin of the neonates. This method proved to be a failure because of the poor correlation. The second method was mathematical. By comparing the 'expected' frequency of various mother-infant ABO combinations (based on the ABO distribution of our local population) with the 'observed' frequency of a cohort of infants with severe neonatal jaundice, it was found that only two combinations (O-A and O-B mother-infant pairs) were responsible for ABO-HDN, for which the incidence was 1 in 5 among infants with a serum bilirubin level of 300 mumols/L or more. PMID- 2206616 TI - Two cases of cri-du-chat syndrome with mild phenotypic effect but with different size of 5p deletion. AB - The clinical and cytogenetic findings of two cases of cri-du-chat syndrome are described. Both cases were females with only slight growth delay, moderate mental disability and minimal phenotypic effects. The mild phenotype was difficult to correlate with the karyotype, which on GTG and RBG banding showed that each had a regular de novo 5p deletion. The deletion in Case 1 was terminal - 46,XX,del(5) (pter----p15.2:) and in Case 2 it was interstitial - 46,XX,del(5) (pter--- p15.2::p13.3----qter). The deletion in Case 2 was considerably larger than in Case 1. PMID- 2206618 TI - Management of a hydropic infant with congenital heart block. AB - A baby with congenital heart block and hydrops fetalis diagnosed prenatally was delivered at 36 weeks of gestation. Heart failure was controlled with temporary cardiac pacing which was complicated by perforation of the myocardium. She made an uneventful recovery after implantation of a permanent pacemaker. Sjogren's syndrome A antibodies were detected in her serum. Coincidentally, she also had pulmonary valvular stenosis as a structural abnormality. PMID- 2206619 TI - Endemic methicillin-resistant Staphylococcus aureus in a special care baby unit: a 2 year review. AB - During January 1987, methicillin-resistant Staphylococcus aureus (MRSA) was isolated for the first time from a baby admitted to the special care baby unit of a large metropolitan hospital. Over a 2 year period, of 1574 babies admitted to the unit, at least 573 (36.4%) became colonized with the organism. Only nine (1.6%) developed significant infectious morbidity and one baby died. Minor infections occurred in a further 35 (6.1%). The outbreak remained uncontrolled despite rigid infection control measures. Subsequent emphasis on hand washing, in service education and provision of weekly review of the MRSA colonization rates have failed to eliminate the organism from the unit. PMID- 2206620 TI - Serum digoxin concentration in a neonate with renal and hepatic impairment. AB - This report demonstrates the questionable usefulness of monitoring digoxin concentrations using the available immunoassays in some clinical situations. The patient reported here showed three characteristics (being a neonate with hepatic and renal impairment) that are associated with the presence of digoxin-like immunoreactive substances. The patient's serum digoxin concentration continued to rise to a peak of 43.7 nmol/L (34.1 ng/mL), 19 days after administration of the drug was discontinued. PMID- 2206621 TI - Glycerin-induced haemolysis associated with the use of haemofilter. PMID- 2206623 TI - Nursing administration research, Part One: Pluralities of persons. PMID- 2206622 TI - Home health care. PMID- 2206624 TI - Education for critical care nursing. PMID- 2206625 TI - Nursing research education. PMID- 2206626 TI - Acquired immunodeficiency syndrome. PMID- 2206627 TI - Interpersonal communication between nurses and patients. PMID- 2206629 TI - Prevention of pressure sores. PMID- 2206628 TI - Cardiovascular nursing research. PMID- 2206630 TI - The effects of stress during the brain growth spurt. PMID- 2206631 TI - Smoking cessation: research on relapse crises. PMID- 2206632 TI - [Functional brain study by radionuclide neuroimaging]. PMID- 2206634 TI - [Dynamic observation by PET in epilepsy]. PMID- 2206633 TI - [Positron emission tomography and basal ganglia functions]. PMID- 2206635 TI - [One and a half syndrome and MRI--a case report and functional neuroanatomy of the syndrome]. AB - This is a case report of 63 year old men who presented one and a half syndrome with ipsilateral peripheral type facial palsy due to lacunar infarct. MRI taken one week after the onset (TR 2000, TE 38) demonstrated small high intensity lesion, 4 mm in diameter, located at the dorsal portion of pontine tegmentum, contacting with the floor of 4th ventricle. This MRI coincides with the lesion limited to the abducens nucleus and genu of facial nerve. Traditionally, projections from the PPRF to the ipsilateral abducens nucleus and opposite MLF was postulated. Recently, however, experiment on monkey and autopsy cases showed projection from abducens nucleus, instead of PPRF, to the opposite MLF has been proposed. MRI findings in this case support the latter hypothesis. It is expected that, with the advent of MRI, more meticulous functional neuroanatomy will be developed. PMID- 2206636 TI - [Experimental study on the difference of ischemic threshold between cerebral cortex and thalamus with middle latency auditory evoked potentials]. AB - Middle latency auditory evoked potentials (ML-AEPs) have not yet been established as a device of assessing neurological events because their origins have not been definitely identified. In this study, we assessed the neurological usefulness of MLA-EPs through experimental approach using canine models of acute ischemia localized within the cerebral cortex or thalamus. Two types of localized cerebral ischemia were produced in mongrel dogs by clipping of major cerebral arteries and inducing of hypotension; they were, unilateral cortical ischemia involving the right primary auditory area (group A) and unilateral thalamic ischemia involving the right medial geniculate body (group B). Using these two ischemia models, auditory evoked potentials (AEPs) were intracranially and extracranially recorded in addition to the measurement of local cerebral blood flow (1-CBF). Prior to the induction of ischemia, it was confirmed that positive waves with a latency of 20 ms (P20) were evoked in the bilateral primary auditory areas by sound stimulation (90 dB 5 Hz click) given to the ear contralateral to the planned ischemic side in both groups. The right P20 disappeared when the 1-CBF in the right primary auditory area decreased below the ischemic flow threshold of synaptic transmission failure, approximately 18 ml/100 g/min, in group A, and when the 1 CBF in the right medial geniculate body decreased below the threshold, 10 ml/100 g/min, in group B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206637 TI - [Recent advances in evoked potentials: physiological bases for understanding somatosensory evoked potentials]. PMID- 2206638 TI - [An autopsy case of amyotrophic lateral sclerosis associated with cervical syringomyelia]. AB - An autopsied case of amyotrophic lateral sclerosis complicated by cervical syringomyelia was reported. The case was a 59-year-old man, who first noticed weakness of both lower extremities at 54-year-old. The weakness spread to both upper extremities within 2 years. Cervical myelography revealed multi-level cervical spondylosis and anterior fusion of C5-C7 was done. But the weakness and atrophy of proximal muscle, diminished deep tendon reflex on upper extremities, hyperreflexia and pathological reflexes on both legs, tongue fasciculation and respiratory muscle weakness developed successively, and the patient died of respiratory distress at 59-year-old. Autopsy revealed multiple independent four syrinxes located at the level between C2-C7. One of these syrinxes had ependymal cell lining and thought to be idiopathic syringomyelia. The other three syrinxes were considered to be the cavitation in association with cervical spondylotic myelopathy. Degeneration and decreasing of spinal anterior horn cells, atrophy of medullary pyramis and Bunina bodies were observed as features of typical amyotrophic lateral sclerosis. Cervical spondylosis as causative lesion of multiple syrinxes was discussed, and relationship between ALS and the syrinxes was not indicated clearly. PMID- 2206639 TI - [An autopsy case of generalized seizures, myoclonus, blindness and deafness]. AB - We have reported the clinical and autopsy findings in a case with generalized seizures, myoclonus, blindness and deafness which was accompanied by stroke-like episodes. This case was diagnosed as mitochondrial encephalomyopathy, lactic acidosis & stroke-like episodes (MELAS) from these findings. Solitary and continuous lesions of softening were distributed in both hemispheres, more severely in the frontal and occipital poles. These lesions did not correspond to a vascular supply. The pulvinar, lateral and medial geniculate body of the thalamus, cerebellar vermis and dentate nucleus had small lesions of softening. The cortical lesions occurred mainly in layer 4, and the most prominent lesions among them appeared cystic, involving the subcortical white matter, but nerve cells in layer 1 and 2 were preserved. Proliferation of small blood vessels was seen around the softening areas. Electron microscopy revealed increased mitochondria in endothelial cells of these vessels, abnormal dense bodies in skeletal muscle cells and tightly packed mitochondria in choroid plexus epithelial cells. Immunohistochemical study suggested that vimentin positive cells were seen around lesions and proliferated vessels are different from those seen in the intact tissues. PMID- 2206640 TI - [Assessment of cerebral infarction by MRI--particularly fogging effect]. AB - Fogging effect in cerebral infarction was studied by MRI in a 51-year-old male patient. Initial symptoms consisted of mild disturbance of consciousness and left hemiparesis. MRI examination was performed 2, 13 and 22 days after onset and the results were compared with CT findings during the same period. CT on day 2 revealed a wide of infarction in the region of the middle cerebral artery including the basal ganglia. The presence of a fogging effect was seen by CT on day 12 and MRI revealed a high signal intensity in the region of the basal ganglia in T 1 image, a high signal intensity in the peripheral region and a low signal intensity in the center in T 2 image. It was possible to define the lesion as the ordinary infarcted lesion by the subsequent CT and MRI. MRI indicated the infarct lesion was to be a high signal intensity in T1 image and a high signal intensity in the periphery and a low signal intensity in the center in T 2 image. It was concluded that these findings indicated hemorrhage, strongly suggesting that the cause of the fogging effect was hemorrhagic infarction. PMID- 2206641 TI - [Test of non-invasive PVI measure with a fiber-optic pressure monitoring device in head injured patients]. AB - At present, method for determining pressure volume status in head injured patients must be obtained via analysis of pressure response to bolus injections into the ventricular catheter system. The concept introduced by Bray of extracting Pressure Volume Index (PVI) measures from analysis of the pulse pressure centroid presents a less invasive technique and provides PVI data continuously. The objective of this study was to test the application of the system which incorporated the Bray concept to PVI measures in head injured patients. The centroid of frequency power spectrum was provided continuously by a computer system linked to the bedside monitor. The computer incorporated the Bray concept for PVI estimation. These values were compared with PVI measured by conventional bolus technique. We tested the system using ICP pulsating wave form delivered from a fiberoptic pressure monitoring system in brain tissue in two different band-width (Narrow band-width: 4-8 Hz, Wide band-width: 4-15 Hz). PVI studies using bolus fluid injection or withdrawal were conducted at least twice a day and usually each study consisted of 3 to 6 injections or withdrawals to obtain a study average PVI. These study average were correlated with the centroid obtained during the same study interval in 17 head injured patients of Glasgow Coma Scale (GCS) 8 or less. The correlation of the centroid and PVI in the wide band-width group was significant (p less than 0.01, r = 0.77), however, in the narrow band-width group, the correlation was not significant (r = 0.07, N.S.).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206642 TI - [Elevation of intracranial pressure during hemodialysis--continuous measurement of cerebrospinal fluid pressure in a patient with acoustic neurinoma]. AB - Intracranial pressure (ICP) was continuously monitored in a thirty-two-year-old female of acoustic neurinoma complicated with chronic renal failure. Severe headache with vomiting has begun to appear during hemodialysis for several months, prompting a diagnosis of an obstructive hydrocephalus. Continuous ventricular drainage was placed after admission and changes of ICP were monitored during hemodialysis. Dynamic changes of electrolytes, protein, sugar, urea nitrogen, and creatinine levels in the cerebrospinal fluid (CSF) as well as osmolarity were measured every one hour during the hemodialysis. An increment of ICP started to occur gradually after initiation of hemodialysis reaching the maximum value 23 minutes later. It was spontaneously decreased to the initial level 8 minutes later followed by fluctuations thereafter consisting of the changes of 20 to 30 mmHg. A remarkable rise in osmotic pressure in CSF has been observed corresponding to the rise of ICP which created a large difference from the blood osmotic pressure that consistently decreased following the onset of hemodialysis. Whereas, the absolute values of all measured factors including electrolytes and urea nitrogen in CSF have decreased consistently which did not seem to contribute intermittent increment of osmotic pressure of CSF. The cause of ICP increment in our case was considered mainly due to increase of water content in the brain tissue caused by the widening of osmotic gradient between the CSF and blood, although the substances responsible to the actual increase of CSF osmotic pressure remained unclear. PMID- 2206643 TI - [Magnetic resonance imaging of subarachnoid hemorrhage due to ruptured intracranial aneurysm]. AB - We report MRI (magnetic resonance imaging) findings of 31 cases with subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysm. Among these cases, 25 were studied within 72 hours after onset of SAH. A resistive type MRI scanner operating at a field of 0.2 Tesla was used in obtaining inversion recovery (IR) and saturation recovery (SR) images. IR 1500/43/400 (T1 weighted image, T1W), SR 1000/60 (SR image) and SR 2000/100 (T2 weighted image, T2W) were chosen for analysis. The SR image was usually adopted and coronal and/or sagittal images were added when there was enough time for examination. Slice thickness was 10 mm and slice interval was 15 mm. The scan was not necessarily aimed at the visualization of aneurysm itself. 1) In the acute phase of SAH, subarachnoid spaces near the ruptured aneurysm were appeared as isointensity areas on T1W and as high intensity areas on SR image. In the subacute phase, they were depicted as high intensity areas on both T1W and SR images, and as high intensity areas on T2W. 2) Intraventricular hemorrhage was visualized as a niveau-like high intensity area, especially, within the posterior horns on the SR images. 3) SR and T2W images were suitable for detection of aneurysm itself. In a resistive type scanner, small aneurysms were not easily visualized due to the lack of high resolution. However, 29% of aneuysms, which were not giant, could be visualized on MRI. 4) Identification of intracerebral hemorrhage and cerebral ischemia from various causes was easy on both T1W and T2W images.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206644 TI - [Hemodynamic studies on the vertebral artery system during the vertebral arterial surgery]. AB - Few hemodynamic studies on the vertebral artery system in the human can be seen. The authors measured the vertebral arterial blood flow (VAF) with an electromagnetic flow meter in 45 patients who obtained vertebral arterial surgeries. The patients showing vertebrobasilar insufficiency such as vertigo and drop attack had serious kinking and stenosis at the first portion of the vertebral artery. The effects of induced hypotension by trimethaphan camsilate, induced hypertension by phenylephrine, cervical epidural anesthesia and induced hypertension under epidural anesthesia on the VAF were investigated. During the control state, mean systemic arterial blood pressure (SABP), mean VAF were 97 mmHg and 54 ml/min, respectively. The effects of varied SPBP were analyzed by (delta mean VAF/mean VAF)/(delta mean SABP/mean SABP), (delta V/delta S). The delta mean VAF and delta mean SABP indicated varied mean values of VAF and SABP, respectively. Mean SABP was varied significantly by about 25% in each method. The delta V/delta S in induced hypotension, induced hypertension, epidural anesthesia and induced hypertension under epidural anesthesia were -0.05, 0.07, 0.90 and 0.61, respectively, on the average. Induced hypotension by epidural anesthesia and induced hypertension under epidural anesthesia presented significant changes in mean VAF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206645 TI - [Denture stomatitis. 2. Histopathological, diagnostic and therapeutic aspects]. PMID- 2206646 TI - [Internal tooth resorption]. PMID- 2206647 TI - [Surgery of palatal and mandibular torus]. AB - Surgical techniques for the exeresis of torus, both palatal and mandibular. We observe indications, contraindications and complications as well as enumerate all the right events to realize correctly the said techniques. PMID- 2206648 TI - [Comparative surface microanalysis of Branemark implants which fail to osseointegrate]. AB - The chemical composition and topography of the implant surface are important in order to understand why the human immunological system responds with different interphases to different materials. We are presenting a comparative study of the surfaces of 16 Branemark oral implants, 11 of which came from retreived samples that did not achieve, or failed osseointegration and five control samples which were never implanted. The period of implantation in human maxilla varied between 2 and 22 months. After cleaning and sterilization, we studied the topography, surface chemical composition and thickness of the oxide layer. The results obtained with scanning electron microscope (SEM) di not detect any significant topographical differences among the samples. X-rays espectrographic microanalysis (EDS) showed very similar composition, titanium and amounts smaller than 0.5% of other elements, in the outermost micron of the analyzed samples. The Auger espectroscope (AES) revealed, in the last monolayers, greater oxide thickness in accordance with the time elapsed from implantation and found considerable percentage differences in the amount of carbon and silicium, which could be attributed to handling. This places the extracted samples out of the acceptable statistical limits of contamination which were established for the reference surface by long term clinical studies. PMID- 2206649 TI - 'Transfer of patients from the CDS to the GDS'. PMID- 2206650 TI - 'Intravenous sedation in general dental practice--why oximetry?'. PMID- 2206651 TI - Evaluation of a new antiseptic-containing alginate impression material. AB - A comparison was made of the disinfection achieved in impressions taken in Blueprint Asept alginate impression material and those taken in the plain brand of this material disinfected by immersion in 1% Hycolin solution for one minute. The plain Blueprint impression material without disinfection was used as a control. Impressions were taken of dies which had been contaminated with 0.75 ml of saliva from each of 20 volunteers. The surfaces of the impressions were used to inoculate Wilkins-Chalgren agar plates immediately and after 1 and 2 hours' storage of the impressions. The number of organisms recovered from the surface of the Blueprint Asept impressions was 1.5% of the control immediately after removal from the dies and complete disinfection was observed within one hour. In contrast, the number of organisms recovered from the surface of the impressions disinfected with 1% Hycolin solution was 30% of the control immediately after disinfection, and viable organisms could still be recovered after 2 hours' storage. Blueprint Asept impression material appears, therefore, to provide a high degree of disinfection when compared with the plain material treated with 1% Hycolin solution for one minute. PMID- 2206652 TI - Temporary elective tooth separation as a diagnostic aid in general dental practice. AB - This study examined the feasibility, acceptability and potential diagnostic value of using a 'blanket' technique for placing elastomeric separators as a diagnostic aid in a general practice situation. Five practices were visited and 211 children between 5 and 15 years were examined. All 211 children accepted the 'clinical without separators' examination, 37 children were unwilling to have the radiographic examination and 12 of the 146 children who required separators refused or removed them. The use of the technique as a routine aid was acceptable to the host practitioners, the parents, most of the patients and to the clinician conducting the study. The method was shown to be valuable in revealing additional approximal lesions. A total of 703 lesions were disclosed by the 'clinical with separators' method, compared with 479 diagnosed by routine clinical examination alone. As many of the additional lesions were at the precavitation stage, this information could be used to target those patients with special needs for preventive care. While the larger dentinal lesions revealed by temporary elective tooth separation were confirmed by bitewing radiographs, many of the small precavitation lesions were not. The results showed, however, that bitewing radiographs were still an important diagnostic aid, especially in the deciduous dentition. Elastomeric separators may have a role as a diagnostic aid in conjunction with bitewings, rather than as a replacement for them. PMID- 2206653 TI - Surgical emphysema during restorative dentistry. AB - A case of surgical emphysema which occurred during a routine restorative dental procedure is presented. The differential diagnosis and management of this condition is discussed. Judicious use of intra-oral dental instruments using compressed air is advised. PMID- 2206654 TI - A radicular dens invaginatus. AB - A case of the radicular type of dens invaginatus involving a mandibular third molar is reported. The clinical presentation and histopathology are described and the development and significance of such lesions discussed. PMID- 2206655 TI - Saliva and dental health. Clinical implications of saliva: report of a consensus meeting. PMID- 2206656 TI - Analysis of patterns of use of an emergency dental service. AB - When establishing an emergency dental service, its success must, to a large extent, depend on such factors as the operating times, the catchment area, and the types of problems presented by clients, be they genuine emergencies or not. This paper reports the experience gained from one such emergency service, in the hope that it may be of value to others proposing to establish something similar. PMID- 2206657 TI - The new contract and referendum. PMID- 2206658 TI - 'Reasonable remuneration?'. PMID- 2206659 TI - 'Intravenous sedation: the risk to the dentist'. PMID- 2206660 TI - 'Medical management of trigeminal neuralgia'. PMID- 2206661 TI - Anaesthetic accident. PMID- 2206662 TI - 'An enduring record'. PMID- 2206663 TI - 'Management of the unerupted maxillary canine'. PMID- 2206664 TI - Information requirements--what does the profession need? PMID- 2206665 TI - Restorative treatment thresholds reported to be used by dentists in Scotland. AB - A questionnaire was sent by post to all dentists practising in the General Dental Service and the Community Dental Service in Scotland; 72% of them (1127) completed and returned it. Three sets of descriptions of carious lesions, ordered on the basis of increasing degree of severity, were supplied. One was based on the radiographic appearance of lesions affecting approximal surfaces, the others on the visual/tactile appearance of lesions affecting free smooth surfaces (buccal and lingual) and occlusal surfaces. For each type of surface the dentists were asked which description indicated the minimum point at which a filling ought to be provided (restorative treatment threshold) in 12- and 30-year-old patients. Overall, the majority of dentists said they would intervene earlier in the case of a 12-year-old than in the case of a 30-year-old patient. Many dentists indicated they would fill an approximal lesion whose radiolucency was confined to the enamel (44.2% for a 12-year-old, 20.1% for a 30-year-old). A further substantial proportion gave a response which suggested that the amelodentinal junction would be the critical decision point (25.8% for a 12-year-old, 19.3% for a 30-year-old). Many also felt that a filling ought to be provided prior to visible cavitation for lesions of the occlusal surfaces (55.1% for a 12-year-old, 22.1% for a 30-year-old); fewer advocated the same treatment threshold for lesions affecting buccal/lingual surfaces (24.1% for a 12-year-old, 9.2% for a 30 year-old).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206666 TI - The prevalence of clinically undetected occlusal dentine caries in Scottish adolescents. AB - During the third examination of a 3-year anti-caries dentifrice study, bitewing radiographs were read to detect occlusal, as well as approximal caries lesions in 2623 subjects aged 14-15 years. These analyses showed that 1.4% of 2107 upper molars and 7.2% of 2288 lower molars (P less than 0.001), previously scored as clinically 'sound', were carious at a radiographic Grade '3' score (dentinal involvement), and 0.2% had radiographic pulpal lesions. However, for teeth which had been deemed as having a 'suspicion' of caries clinically, but which a 0.6 mm blunted probe would not enter, 29.1% of lower molars had definite radiographic evidence of dentinal caries as compared to only 7.6% of upper molars (P less than 0.001), and a further 0.5% exhibited pulpal extension. In addition, 23.9% of lower premolars also showed dentinal involvement in this group. Overall, 12.1% of lower molars and 3.1% of upper molars showed definite radiographic evidence of occlusal caries in the absence of a firm clinical indication. Thus, the use of bitewing radiographs would appear to be a most helpful adjunct to clinical caries diagnosis, not only of approximal lesions, but also for the detection of early occlusal caries, in these days of generally available topical fluoride. PMID- 2206667 TI - Orofacial pain in patients with sickle cell disease. AB - The potential danger of low oxygen tension to patients with sickle cell disease is widely known. However, less well known is the phenomenon of patients with sickle cell disease presenting with toothache in the absence of any dental pathology. This study investigated the experience of orofacial pain in three matched groups, comprising patients with sickle cell disease, sickle cell trait and patients with no known blood dyscrasia. There were no differences in pain experience between those groups with sickle cell trait and no known blood dyscrasia. The sickle cell disease patients experienced significantly more orofacial pain in the same 12-month period than the other groups. The pain was also more frequent and of longer duration. In two-thirds of those sickle cell disease patients who experienced toothache, no dental pathology was found, in direct contrast to patients with trait or no known blood dyscrasia. Sickling of blood cells within the dental pulp in a sickle cell crisis may result in pain within teeth. These patients may then present as experiencing toothache in the absence of any dental pathology. General dental practitioners should be aware of this phenomenon when providing care for these susceptible patients. PMID- 2206668 TI - Thinking about anxiety. AB - Dental anxiety is often considered to involve physiological and behavioural changes, but it also involves patients' beliefs and thoughts about treatment. This paper reviews several studies in this area, concentrating on how such thought processes may serve to maintain high levels of anxiety, even in patients who attend their dentist regularly. Some implications of these studies for the treatment of persistent anxiety are outlined. PMID- 2206669 TI - Report of the strategic review of the Dental Practice Board, 1990-2000. AB - The Dental Practice Board has reviewed its strategy for the next 10 years. The review concludes that the DPB should continue with its current role and functions and to be managed within the public sector. There should however, be increased effort to improve efficiency and increased emphasis on monitoring and information. The review, which was carried out by the management of the DPB with the help of Ernst and Young Management Consultants under the general guidance of a joint management and board member committee, was adopted as DPB policy at the April, 1990, Board Meeting. PMID- 2206670 TI - 'Surgeons fear threat of AIDS in the air'. PMID- 2206672 TI - 'Intravenous sedation: the risk to the dentist'. PMID- 2206671 TI - 'Bacteraemia following incision and drainage of dento-alveolar abscesses'. PMID- 2206673 TI - 'Sugar. Is it as dangerous as it's made out to be?'. PMID- 2206674 TI - 'Reported use of sealant restorations in a group of general practitioners in the west of Scotland'. PMID- 2206675 TI - 'Supplemental and congenitally absent premolar teeth'. PMID- 2206676 TI - A view from inside. AB - There is sometimes an aspect of a disease that can only be uncovered by surgical exposure in surgical cases and, in spite of all the modern scanning and pathological investigations, by the assembly of the patient's history and symptoms in medical cases. My knowledge of Parkinson's disease is minimal, but I am a trained observer and I have attempted to present a brief study of the condition from 'inside looking out' in the hope that it will assist in expanding clinical rapport. PMID- 2206677 TI - HIV update. PMID- 2206678 TI - Complete denture construction in general dental practice: an update of the 1970 survey. AB - A survey was carried out on materials and techniques used for complete denture construction in general dental practice, by means of a postal questionnaire sent to a random sample of 1000 dentists whose names were taken from the BDA membership. There was a 71.5% response. The results obtained are compared with a similar survey undertaken in 1970. The majority of practitioners still provided dentures totally or mainly within the NHS. Whilst the demand for complete dentures was reported as having remained stable, there has been considerable reduction in the numbers of dental technicians employed by general dental practitioners. Alginate remains the impression material of choice and the majority of impressions were sent to a commercial laboratory for pouring. Although still the most popular, the use of the plane-line hinge articulator has reduced and there has also been a continued reduction in the use of porcelain teeth. The importance of a cross-infection policy is highlighted. There were conflicting opinions expressed on the role of implants in general dental practice. Many respondents took the opportunity to comment on the status of dental prosthetics under the NHS and most criticised the fee structure. PMID- 2206679 TI - Variation in powder/liquid ratio of a restorative glass-ionomer cement used in dental practice. AB - This study investigates the powder/liquid ratios of a glass-ionomer restorative (ChemFil II, Dentsply) mixed in clinical practice. Twenty-two dental surgery assistants (11 from general practice; 11 from a dental hospital) mixed this cement as they would for clinical use. Samples were taken of three mixes from each assistant and the powder/liquid ratios were derived from weight loss on dehydration. A wide range of ratios were obtained, but in no case was the manufacturer's recommended ratio of 6.8:1 achieved. The consistency measured in accordance with BS 6039 showed the cement at 6.8:1 to be less fluid than the requirements of the standard and other glass-ionomer restoratives. When tested at the mean ratio used in practice, 5.0:1, the consistency complied with BS 6039, but the compressive and diametral strengths did not, being about half the values found at 6.8:1. It was concluded that this restorative was often mixed in practice at much lower powder/liquid ratios than that recommended by the manufacturer and that this would impair the cement's mechanical properties. PMID- 2206680 TI - A survey of general anaesthesia and sedation in dental practice in two cities. AB - Using a postal questionnaire, the use of general anaesthesia and sedation in general dental practice in two cities over a 4-week period was investigated. Questionnaires were sent to a random sample of one in five dental practitioners in Bristol and Sheffield, and an 82% response rate was attained. More practices in Sheffield administered general anaesthesia than those in Bristol. The differences between the facilities provided are discussed. Equipment and facilities have improved since a larger survey was described in 1976, but the use and availability of monitoring equipment has changed little since then. The results reflect the decline in the use of general anaesthesia in dental practice seen nationally. The survey provides an insight into the current anaesthetic services provided in general dental practice in two cities, both of which contain dental hospitals, and provides a basis for the design of a protocol for a further national survey. PMID- 2206681 TI - Postal commemoration for centenary of Melbourne's Royal Dental Hospital. PMID- 2206683 TI - Diagnosis and prevention of temporomandibular joint (TMJ) or odontostomatognathic (OSG) injury in dental practice. AB - Malpractice lawsuit cases due to temporomandibular joint/soft tissue injuries following dental therapy are increasing. Therefore, dentists and their staffs must know how to recognize, document and avoid any possible aggravation or precipitation of TMJ disorder. TMJ anatomy, biomechanics and mechanisms of TMJ injuries are presented. Etiological factors such as psychological factors, parafunctional activities, malocclusion, trauma, iatrogenic causes, systemic conditions, developmental disorders, neoplastic growth or medications are discussed. Preventive measures addressed include: history-taking, patient examination, complete records, the assessment of the patient's general condition, documentation of pre-existing findings, informing and educating the patient, performing only the necessary procedures, modifying appointments, selecting less traumatic dental techniques, avoiding sudden occlusal alterations and preparedness to handle unwanted complications. PMID- 2206682 TI - The increasing cost of health care--doctors suffer as well! AB - At long last there does appear to be general agreement that all is not well with the American health care system. Costs are out of control and the bureaucracy that has been spawned to control costs and administer the financial aspects of health care has developed a mind of its own. Two recent problems within our own department at the University of California, San Francisco, have shown that even doctors can be on the receiving end of these problems, with amusing but potentially serious consequences. PMID- 2206684 TI - Ceramic inlays: an alternative for esthetic restorations in posterior teeth. PMID- 2206685 TI - Chest radiography in the intensive care unit. Indications for radiography and effects of selective archiving of films. AB - Consecutive chest radiographs (n = 2,303) in 601 patients in the intensive care units (ICU) were analyzed with regard to main disease and indication. Two thirds of the patients were transferred for routine post-operative treatment, 14 per cent mainly for cardiopulmonary insufficiency. The remainder were referred because of various clinical conditions. The main indications for chest radiography were routine radiographic follow-up and/or control of the position of catheters, tubes, drainages etc. (50%). Obvious clinical indications appeared in only about 1/4 of the patients. When the patients were discharged from the ICU all chest radiographs were analyzed with regard to their predicted future value. Films considered not worth storing were removed and stored in a separate archive (57%). During a 15-month follow-up period none of the removed films were requested, indicating that a substantial number of films can be sorted out continuously. The possibility to reduce and to 'clinically compress' the amount of data in a future digital picture archive is emphasized. PMID- 2206686 TI - Coronary angiography and thallium-201 single photon emission computed tomography in multiple vessel coronary artery disease. AB - Polar presentations of selective coronary angiography and myocardial 201Tl SPECT were compared in 141 patients with multiple vessel disease, 80 with 3-vessel disease, 34 with 2-vessel disease and 27 post-bypass patients. Perfusion defects were present in 125/141 patients (89%) and were located within the area supplied by 194/359 stenotic arteries (54%) and 9 non-stenotic arteries. The type and extent of disease was correctly indicated by 201Tl SPECT in 16/80 patients (20%) with 3-vessel disease, 5/34 patients (15%) with 2-vessel disease and 8/27 post bypass patients (30%). Perfusion defects indicated the artery with the most severe lesion in 107/125 patients (86%). False negative isotope studies were present in 15 patients (11%). PMID- 2206687 TI - Arterial segmental vasoconstriction in hypercholesterolaemic patients. AB - Regular, wave-like constriction in medium-sized arteries, arterial segmental vasoconstriction (ASV), has been observed at arteriography and described by many authors. We found ASV in arteriograms of the superficial femoral artery in 13 of 107 hypercholesterolaemic patients, enrolled in the Probucol Quantitative Regression Swedish Trial (PQRST). The arteriograms were digitized and studied with a quantitative computer-assisted technique. The frequency of ASV was higher than has been reported earlier in clinical materials, possibly because of an increased vasoreactivity in hypercholesterolaemia, as recently observed experimentally. The ASV patients were, on average, younger, had lower blood pressure and less atherosclerosis, than the non-ASV patients. ASV was not found in any of the 19 patients in the material who either had symptoms of peripheral vascular disease or arteriographically verified arterial occlusions. No significant correlations with smoking habits or serum cholesterol levels were found. A computer-based index of ASV and measurement of ASV wavelength are discussed. PMID- 2206688 TI - Ultrasonography and Doppler Duplex compared with angiography in follow-up of mesocaval shunt patency. AB - Thirty-four patients with portal hypertension of various etiologies were operated upon with an interposition mesocaval Goretex graft. During a period of 6 years 84 angiographic and ultrasonographic (US) examinations (53 B-mode, and 31 Doppler Duplex) were performed, with few exceptions within 3 days. Angiography served as the 'gold standard'. Shunt patency was correctly interpreted as normal in B-mode US in 38 examinations. Shunt occlusion, definite or probable, was seen in 12 B mode examinations, where angiography demonstrated occlusion in 6 and patency in the remaining 6 shunts. Shunt occlusion was not observed sonographically in one examination. US was technically inadequate on two occasions. Doppler Duplex showed shunt patency in all 31 examinations, which was correct according to angiography. Both B-mode US, in 6 out of 6 examinations, and Doppler Duplex, in 7 out of 9 examinations failed to reveal shunt stenosis. Five patients with abundant venous collaterals (in one case with aberrant vascular anatomy) were not possible to evaluate even after the introduction of Doppler Duplex, which otherwise facilitated the evaluation. We suggest that US including Doppler should be the primary modality for follow-up in patients with interposition mesocaval Goretex grafts. PMID- 2206689 TI - Diagnosis and percutaneous treatment of pyogenic hepatic abscesses. AB - Twelve patients with intrahepatic abscesses were examined with computed tomography and ultrasonography between 1979 and 1988. The median size of the lesions was 7 (1-12) cm. They were in 8 patients located only in the right liver lobe and in 3 in both liver lobes. On ultrasonography the echogenicity of the abscesses varied from hypo- to hyperechoic which is consistent with tumours. The final diagnosis of abscess was achieved by fine needle puncture and aspiration for bacterial culture. Nine patients were treated with percutaneous drainage. 3 of them with two catheters, and all received systemic antibiotic treatment. All patients survived the treatment. PMID- 2206690 TI - Double contrast small bowel enema in a case of selective duodeno-jejunal amyloidosis. AB - Double contrast small bowel enema in a patient with selective amyloidosis of the duodenum and jejunum revealed an unusual radiologic pattern, mimicking multiple polyposis. Many submucosal polypoid lesions, sessile or pedunculated, were scattered throughout the duodenum and proximal jejunum. The lesions had smooth borders and did not show any retraction at the base. Other typical radiologic patterns of intestinal amyloidosis described in the literature were not observed in the present case. Differential diagnosis from multiple polyposis and diffuse lymphoproliferative neoplastic diseases is discussed. PMID- 2206691 TI - CT demonstration of fistulae in patients with gynecologic neoplasms. AB - Ten women treated for gynecologic neoplasms (8 cervical carcinomas, one vaginal and one endometrial carcinoma) were found at computed tomography (CT) to have a fistula although only 5 patients had symptoms that could be related to a fistula. Five women had vesico-vaginal fistulae, 2 recto-vaginal, 2 entero-cervical and one a vulvo-pubical fistula. We regard CT as the radiologic method of choice in diagnosing gynecologic fistulae. PMID- 2206692 TI - Magnetic resonance imaging of the bone marrow in patients with acute leukemia during and after chemotherapy. Changes in T1 relaxation. AB - Twenty-seven patients with acute leukemia were examined at the time of diagnosis with MR imaging and in vivo T1 relaxation time measurements of the hemopoietic bone marrow. A 1.5 T whole body magnetic resonance scanner was used. Twenty of the patients had follow-up examinations in relation to chemotherapy. Bone marrow biopsies from the posterior iliac crest were obtained within a short time interval of all MR examinations. At the time of diagnosis, T1 relaxation times were increased significantly in all the leukemic patients, compared with 24 age matched controls. A decrease in T1 relaxation time towards or into the normal range was observed in 10 patients who obtained remission. The T1 relaxation time remained prolonged in 6 patients who failed to obtain remission during chemotherapy. Four patients, who obtained remission with concomitant decrease of T1 values towards or into the normal range, also showed prolongation of T1 relaxation time in relation to leukemic relapse. The results indicate that changes observed in T1 relaxation times of the hemopoietic bone marrow in patients with acute leukemia reflect changes in disease activity, and, that serial measurements of T1 values may provide clinically useful information with the possibility for identification of residual disease in regions inaccessible for biopsy. PMID- 2206693 TI - Quantitative evaluation of hyaline cartilage disorders using flash sequence. I. Method and animal experiments. AB - A method for quantitative evaluation of hyaline cartilage signal intensities has been developed in an experimental study of 6 swine knees with different types of arthritis. A FLASH sequence with TR 50 ms, TE 10 ms and flip angles of 5, 10, 20, 25, 30, 35, 50 and 90 degrees was employed. Two parameters of the signal intensity flip angle curves proved to be useful for tissue characterisation: The initial increase (A) and the maximum (M). PMID- 2206694 TI - Quantitative evaluation of hyaline cartilage disorders using flash sequence. II. Clinical applications. AB - In a prospective clinical study 24 normal volunteers and 106 patients with acute and chronic arthritis, osteoarthritis and post-traumatic alterations of the knee joints were examined. Using the parameters A and M 98 per cent of the pathologic cartilages and 74 per cent of the normal cartilages could be identified. In addition 78.5 per cent were correctly categorized in 5 cartilage classes. The A/M classification proved to be a fast and specific method for evaluation of cartilage disorders with special promise for follow-up examinations during therapy. PMID- 2206695 TI - Osseous temporomandibular joint abnormalities in rheumatic disease. Computed tomography versus hypocycloidal tomography. AB - Computed tomography (CT) of the temporomandibular joint (TMJ) was compared with hypocycloidal tomography in 30 joints of 15 adults with rheumatic disease. CT included 1.5 mm thick axial scans (at 1.0 mm intervals) with reformatted oblique sagittal and oblique coronal sections. Multisection (at 2.0 mm intervals) tomography included oblique sagittal and occasionally, oblique coronal sections. CT demonstrated bone abnormalities in 21 and tomography in 20 joints, indicating high agreement between the imaging modalities regarding number of abnormal TMJs. Bone structures were, however, better visualized by multiplanar CT due to superior contrast and spatial resolution particularly in the most lateral and medial parts of the joint, indicating superiority of CT for depicting subtle bony TMJ abnormalities in patients with rheumatic disease. PMID- 2206696 TI - Pelvic inclination and spatial orientation of the acetabulum. A radiographic, computed tomographic and clinical investigation. AB - In a study of 40 young adults the pelvic inclination measured by a specially constructed inclinometer was found to be the same in the supine and standing positions when related to the horizontal and frontal planes, respectively. Consequently supine CT measurements of the hip are also representative of corresponding standing angles. The variations of the acetabular anterversion and the sector angles on CT of the hips in 5 adult corpses were measured by angulating the gantry in increments of 5 degrees to +/- 20 degrees. An approximate linear relationship was found for all parameters, the acetabular anteversion varied 0.5 degree with 1 degree pelvic rotation, and the sector angles 0.7 degree. A theoretic mathematical model for the variation of the acetabular anteversion outside the measured range employing a sine curve is introduced. PMID- 2206697 TI - Systemic, pulmonary and renal haemodynamic effects of intravenously infused iopentol. A comparison in the pig of a new low osmolar non-ionic medium with saline and iohexol. AB - The central, peripheral and renal haemodynamic effects after intravenous infusion (1 ml/s) of high doses (4 mg I/kg) of two low osmolar, chemically and physically similar non-ionic contrast media (iohexol and iopentol) were investigated in 16 pigs. Both contrast media induced a significant increase of mean arterial, mean right atrial, mean pulmonary arterial and mean pulmonary arterial occlusion pressure along with an increase in cardiac output. The systemic vascular and pulmonary vascular resistances were decreased. Renal venous blood flow and renal vascular resistance were not significantly changed after infusion of contrast media. There were no differences in haemodynamic effects between the two media studied. PMID- 2206698 TI - Superparamagnetic particles as gastrointestinal contrast agent in magnetic resonance imaging of lower abdomen. AB - Negative gastrointestinal contrast enhancement can be achieved by oral administration of superparamagnetic particles. Their feasibility for the MR imaging of the female pelvis and lower abdomen was evaluated in studies on 32 follow-up patients with treated gynaecologic cancer. All the applied doses (0.2 1.0 mg particles/ml given in a volume of 600-800 ml) of contrast medium decreased the intraluminal signal. However, there was unpredictable individual variation in segmental distribution, and in some cases only a limited contrast effect was obtained. Image distortion was detected when the applied particle concentration exceeded 0.5 mg/ml, especially of the sagittal sections. PMID- 2206699 TI - Ultrasound guided needle biopsy of skeletal muscle in neuromuscular disease. AB - Guided by ultrasonography percutaneous needle biopsy of skeletal muscle was performed in 24 patients, using the one hand held Biopty system and a 2 mm Tru Cut needle. The specimens were graded with regard to diagnostic quality and utility and almost all specimens (96%) were of highest quality. The use of ultrasonography was helpful in selecting a suitable area for the biopsy and vascular structures could be avoided. The procedure was well tolerated and easy to perform, and no complications were recorded. PMID- 2206700 TI - Ink jet color printing of digital medical images. PMID- 2206701 TI - Friends of nursing: a development and management success. PMID- 2206702 TI - Managing an internal union raid. PMID- 2206703 TI - Leadership: sharing your vision. PMID- 2206705 TI - Muscarinic antagonist binding to intact rat thymocytes. AB - The presence and properties of muscarinic receptors on intact rat thymocytes have been studied by the use of the muscarinic antagonists [3H]-3-quinuclidinyl benzilate (3H-QNB), [3H]-4-N-methylpiperidinyl benzilate ([3H]-NMBP) and [3H]-N methylscopolamine (3H-NMS). The course of binding of 3H-QNB reveals a maximum at 5 min, and shows a subsequent decrease of bound radioactivity, suggesting internalization of the receptor 3H-3-QNB complex. This phenomenon has also been studied by the use of another muscarinic antagonist, 3H-NMPB, which has a faster on and off rate than 3H-QNB, and which may be rapidly displaced by an excess of unlabeled muscarinic antagonist, atropine. Bound 3H-NMPB is highly susceptible to atropine displacement only within the first two minutes of incubation with thymocytes at 37 degrees C. The kinetics of binding of the less lipophilic muscarinic antagonist 3H-NMS to thymocytes, show no maximum as a function of incubation time and 3H-NMS is susceptible to displacement by atropine up to 30 min incubation time with the thymocytes. These data suggest that binding of lipophilic benzilate type antagonists (3H-QNB and 3H-NMPB) may be followed by internalization and/or isomerization of the receptor-benzilate antagnist complex while the 3H-NMS-receptor complex is not subject to these processes. PMID- 2206706 TI - Potential anti-HIV active pyranoid analogs of AZT. PMID- 2206704 TI - Synthesis and single cell pharmacology of potential heterocyclic bioisosteres of the excitatory amino acid antagonist glutamic acid diethyl ester. AB - A series of heterocyclic analogues of glutamic acid diethyl ester (GDEE), an antagonist at central excitatory amino acid receptors, have been synthesized and tested biologically. (RS)-Ethyl alpha-amino-alpha-(3-ethoxyisoxazol-5-yl)acetate (7), (RS)-ethyl 2-amino-3-(3-ethoxy-5-methylisoxazol-4-yl)propionate (16) and closely related analogues were synthesized. Compound 7, a diethyl derivative of the naturally occurring excitatory amino acid ibotenic acid (IBO), was synthesized from 3-hydroxy-5-methylisoxazole (1) via 3-ethoxyisoxazol-5-ylacetic acid (5) and its ethyl ester. Nitrosation of this ester followed by catalytic reduction gave 7. The ethyl ester of IBO, 9, was synthesized in a similar manner from 3-benzyloxyisoxazol-5-ylacetic acid (8). Ethyl derivatives of the synthetic excitatory amino acid 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) were synthesized from 3-hydroxy-4,5-dimethylisoxazole (10) through a diethyl acetylaminomalonate derivative, which upon deprotection gave the 3-ethoxy derivative of AMPA (15). Esterification of 15 gave the diethyl derivative 16 and the ethyl ester of AMPA (18) as well as N-ethylated derivatives of AMPA, 21 and 22 were synthesized. The final products were tested microelectrophoretically. The derivatives 7, 9, 15, 16 and 18 were weak and non-selective excitatory amino acid antagonists, whereas 21 and 22 were found to be inactive. PMID- 2206707 TI - Separation and enrichment of alkylated globin chains as a means of improving the sensitivity of hemoglobin adduct measurements. AB - Measurement of adducts of hemoglobin is a reliable and quantitative method for monitoring exposure to genotoxic chemicals. To make the approach applicable to the low levels of adducts originating from exposure to chemicals in the environment, increased sensitivity of the analytical procedures is required. The method presented here is based on quantitative determination of low levels of adducts after purification and enrichment of chemically modified (adducted) globin chains on CM-Sepharose CL-6B. In the developmental work, human globin was used after alkylation by radiolabelled ethylene oxide, styrene oxide or N-ethyl-N nitrosourea. Ethylene oxide reacts mainly with the amino terminal valine and nitrogens in the imidazole ring of histidine, while N-ethyl-N-nitrosourea has a particularly high reactivity towards free carboxy groups of acidic amino acids. Globin chains with adducts to the carboxy groups were especially easy to separate from the non-modified chains. Ethyl adducts to carboxy groups in hemoglobin were shown to be sufficiently stable in vivo to be used for dose monitoring. PMID- 2206708 TI - Calculation of the cytochrome P-450 redox potential from kinetic data by the Marcus treatment; feasible or not? AB - Using calculations based on the Marcus theory (or linear approximations thereof) and existing rate constant/oxidation potential data, an attempt has been made to estimate the effective standard potential and reorganization energy of the P 450/(P-450)-.couple. Due to the limited data basis, the results only qualitatively indicate that P-450 either must possess an extremely high Eo'Fe(V)/Fe(IV) value (greater than 2.5 V!) or not act as an electron transfer oxidant at all. By similar calculations, it was found that model alkene epoxidation reactions do not follow an ET mechanism. PMID- 2206709 TI - Late potentials as predictors of risk after thrombolytic treatment? PMID- 2206710 TI - Transoesophageal echocardiography improves the diagnostic value of cardiac ultrasound in patients with carcinoid heart disease. AB - Transthoracic and transoesophageal cardiac echocardiography and Doppler investigations were performed in 31 consecutive patients with malignant midgut carcinoid tumours. The transoesophageal images allowed measurement of the thickness of the atrioventricular valve leaflets and the superficial wall layers on the cavity side of both atria. The mean thickness of the anterior tricuspid leaflet was significantly greater than that of the mitral valve--a difference not seen in a control group of age-matched patients without carcinoid tumours and with normal cardiac ultrasound findings. In addition, the edges of the tricuspid leaflets were thickened giving them a clubbed appearance. Tricuspid incompetence was detected transoesophageally in 71% of the patients with carcinoid compared with 57% by transthoracic investigation. The inner layer of the right atrial wall in the carcinoid patients was significantly thicker than that of the left atrium and that of both atria in the controls. Furthermore, patients with other signs of severe carcinoid heart disease had significantly thicker mean right atrial luminal wall layer than those with less or no signs of right heart disease. Transoesophageal cardiac ultrasound investigation improved the diagnostic accuracy and seemed to show the structural changes typical of carcinoid heart disease established by histopathological investigations. PMID- 2206711 TI - Echocardiographic diagnosis of a ruptured aneurysm of the sinus of Valsalva: operation without catheterisation in seven patients. AB - A ruptured aneurysm of the sinus of Valsalva was diagnosed by Doppler, colour, and cross sectional echocardiography in a consecutive series of seven patients. The diagnoses were confirmed at operation without cardiac catheterisation. Examination by pulsed and continuous Doppler echocardiography showed continuous turbulence in six patients with aneurysms rupturing into the right ventricular outflow tract and in the patient with rupture of an aneurysm of the non-coronary sinus into the right atrium. Colour Doppler echocardiography showed turbulent flow across the defects in all seven patients. A ventricular septal defect with aortic regurgitation was detected in one patient and an associated ventricular septal defect in another. Doppler, colour, and cross sectional echocardiography were useful non-invasive techniques for diagnosing a ruptured aneurysm of the sinus of Valsalva without the need for cardiac catheterisation. PMID- 2206712 TI - Geographical clustering of risk factors and lifestyle for coronary heart disease in the Scottish Heart Health Study. AB - A large cross sectional study, the Scottish Heart Health Study, of 10,359 men and women from 22 districts of Scotland was undertaken to try to explain the geographical variation of coronary heart disease mortality. Analysis by district showed that of the classic risk factors only cigarette smoking was strongly associated with heart disease mortality among both men and women. Mean diastolic blood pressure was weakly associated with rates among men and high density lipoprotein cholesterol showed a strong negative association among women. Total cholesterol showed a weak negative association with heart disease mortality, but, because the serum concentrations of cholesterol were uniformly high in all districts, a strong association with mortality would not be expected. In both men and women many dietary factors showed moderate or strong associations with mortality from coronary heart disease in a district--of these a low consumption of vitamin C was most notable. Other factors associated with heart disease included alcohol consumption and serum triglycerides among men, and obesity, physical activity, and serum triglycerides among women. Many factors associated with heart disease showed strong intercorrelations. Clustering of risk factors (including smoking, alcohol, and diet among men, and smoking, diet, and obesity among women) was associated with much of the regional variation in heart disease mortality in Scotland. PMID- 2206713 TI - Replacement of an aortic valve cusp after neonatal endocarditis. AB - Septic arthritis developed in a neonate after an infection of her hand. Despite medical and surgical treatment endocarditis of her aortic valve developed and the resultant regurgitation required emergency surgery. At operation a new valve cusp was fashioned from preserved calf pericardium. Nine years later she was well and had full exercise tolerance with minimal aortic regurgitation. PMID- 2206714 TI - Hyponatraemia secondary to an inappropriately high release of antidiuretic hormone in cardiac tamponade. AB - A spontaneous intrapericardial haemorrhage caused cardiac tamponade in a 29 year old paraplegic man who was being treated with warfarin. The associated persistent hyponatraemia, which was believed to be caused by an inappropriately high release of antidiuretic hormone, rapidly resolved after pericardiocentesis. PMID- 2206715 TI - Aberrant origin of the right coronary artery as a potential cause of sudden death: successful anatomical correction. AB - A man with an aberrant right coronary artery and haemodynamically important prolapse of the mitral valve was successfully resuscitated. The aberrant right coronary artery was thought to be a possible cause of the cardiopulmonary arrest in this patient. Both lesions were corrected at a single operation. PMID- 2206716 TI - Cardiac catheterisation with 5 French catheters. AB - From the beginning of November 1987 to the end of January 1989, 526 coronary arteriograms and left ventricular angiograms were performed with 5 French coronary catheters. In 448 (85%) patients diagnostic pictures were obtained with three standard types of 5 French catheters (No 4 Judkins): that is, left coronary, right coronary, and pigtail catheters. In 60 patients (11.4%) various other 5 French catheters were required to complete the study. In nine patients (1.7%), a 7 or 8 French catheter was used. Major complications causing cardiac arrest or requiring urgent operation developed in five patients. Sixty two patients (11.77%) had minor complications that required sublingual nitrates or a single bolus of atropine, or developed a haematoma that did not need intervention or had a mild reaction to the contrast material. Complications of moderate severity developed in 17 patients (3.2%): severe chest pain, arrhythmia requiring a temporary pacemaker, contrast reaction associated with hypotension, haematoma requiring blood transfusion, or a transient ischaemic episode. There were no deaths. 5 French catheters were used for routine coronary angiography and left ventriculography in 98.3% of patients. There were no major complications related to femoral artery puncture. The routine use of 5 French coronary catheters should increase the feasibility of safe coronary angiography in outpatients and should reduce the cost of this investigation. PMID- 2206717 TI - Can rationing of cardiological services be rational? PMID- 2206718 TI - The last portrait of Willem Einthoven: newly discovered links between Sir Thomas Lewis and Alexander Samojloff. PMID- 2206719 TI - Estimation of the risk of death after acute myocardial infarction from systolic time intervals. PMID- 2206720 TI - [Metal alloys]. PMID- 2206721 TI - [Dental amalgam]. PMID- 2206723 TI - [New dental school]. PMID- 2206722 TI - [Registration of centric relation]. PMID- 2206724 TI - [Mucogingival surgery. An illustrated bibliographic review]. PMID- 2206725 TI - Respiratory care in adults. PMID- 2206726 TI - Alternate modes of mechanical ventilation. AB - As a result of technological progress and a better understanding of respiratory disease processes, new modes of mechanical ventilation for the critically ill patient have been developed. These new methods may offer specific advantages over traditional techniques by avoiding or reducing complications commonly associated with positive pressure ventilation. A thorough understanding of anticipated benefits and potential problems is carefully considered for each mode of mechanical ventilation. Several alternate approaches to ventilatory assistance are discussed. Clinical applications of nursing care are also discussed. PMID- 2206727 TI - New techniques for weaning difficult patients from mechanical ventilation. AB - This article compares the weaning of challenging patients from mechanical ventilation to an exercise training program experienced by many athletes. Physically, the importance of the correction and maintenance of chronic health issues, nutrition, and hydration are explored. Psychologically, the degree of preparedness by both the patient and the health care team is presented. Parameters for predicting readiness to wean that include both objective and subjective indices are gaining more support; two tools for weaning are offered. During the weaning process, reconditioning of the respiratory muscles can be promoted through endurance or strengthening exercises or a combination of both. The quality and quantity of exercise performed must be closely monitored to prevent respiratory muscle fatigue or atrophy. Newer modes of ventilation, including pressure support ventilation, mandatory minute ventilation, and continuous flow, decrease the work of breathing, promote ventilator/patient synchrony, and provide a more dynamic weaning process. All of these modes promote exercise, and augment the physical and psychological components of weaning. Nursing considerations for successful weaning are offered. PMID- 2206728 TI - Planning for successful home mechanical ventilation. AB - Home mechanical ventilation has evolved to permit discharge of patients on portable negative or positive pressure mechanical ventilators. Assessment of the patient for home discharge is initiated by a multidisciplinary team. The nurse, physician, social worker, respiratory therapist, speech therapist, occupational therapist, home health nursing agency, durable medical equipment supplier, and caregivers constitute the team. The crucial links to a successful patient discharge are an involved family and a well-developed plan of care, although patient finances also are important. The nurse develops, coordinates, and implements the teaching plan over a period of 2 or more weeks. The home caregivers provide total care for the patient several days before discharge. The home health agency and the durable medical equipment supplier provide services which ease the transition of care from hospital to home. One alternative to home discharge is placement in an extended care facility. PMID- 2206729 TI - Ventilator versus manual resuscitation bag as the method for delivering hyperoxygenation before endotracheal suctioning. AB - A critical review and analysis of the current research on the efficacy of the ventilator versus the manual resuscitation bag (MRB) as the method of delivering hyperoxygenation/hyperinflation breaths before, during, and/or after endotracheal suctioning (ETS) is presented. Current research findings indicate that hyperoxygenation/hyperinflation breaths at 100% oxygen (O2) delivered via the ventilator have resulted in elevated blood-O2 levels which are either superior or equivalent to the MRB in preventing suction-induced hypoxemia. Delivery of hyperoxygenation/hyperinflation breaths using the MRB results in increased airway pressure, and increased hemodynamic consequences. Guidelines of clinical practice, based on current research findings, are presented. Areas for further research are identified. PMID- 2206730 TI - Negative pressure ventilation: new uses for an old technique. AB - Negative pressure ventilation (NPV), a concept that was used in the 1940s through 1950s to support the victims of the polio epidemic, is regaining popularity. It is being used increasingly to intermittently support respiratory function in patients suffering from a variety of diseases. The use of NPV obviates the need for a surgically placed airway (if the patients' upper airway is intact) and allows the patient to resume many of his or her normal activities. Several types of NPV are available for use and experimentation, and it is strongly recommended that the appropriate type for each patient be chosen. Nursing care of the patient on NPV is essentially the same as that of any chronically ventilator-dependent patient. Issues unique to the patient supported on NPV include: increased potential for aspiration, skin breakdown around the NPV site, and "tank shock." Nursing plays an important role in identifying patients who may be candidates for NPV. Negative pressure ventilation may allow a formally hospital-bound patient the opportunity to be home with family and friends. PMID- 2206731 TI - Closed tracheal suction systems: effectiveness and nursing implications. AB - Closed tracheal suction systems (CTSS) are currently being used to minimize complications associated with endotracheal suctioning. Advantages of CTSS include improved oxygenation, decreased clinical signs of hypoxemia, maintenance of positive end-expiratory pressure, infection control, convenience, cost, and reduced patient anxiety. Some concerns related to use of CTSS include autocontamination, decreased effectiveness, difficult to use, excess negative pressure, and airway trauma. Strategies for reducing these and other concerns are shared. Recommendations for nursing practice and nursing research are discussed. PMID- 2206732 TI - Respiratory care in children. PMID- 2206733 TI - Nursing diagnoses and interventions in bronchopulmonary dysplasia: a case study. AB - Bronchopulmonary dysplasia (BPD) requires collaborative management in the pediatric health care setting. Because of the nature of the medical diagnoses, BPD can be viewed by nurses using selected nursing diagnoses. With the pediatric client, nursing diagnoses can assist the nurse to identify system alterations, and thereby address nursing interventions most appropriate for the child. Nursing interventions are based on collaborative decision making using both medical and nursing diagnoses. This case study will identify selected nursing diagnoses useful in the care of the child with BPD and nursing interventions used to treat frequently occurring health problems. PMID- 2206734 TI - Pulse oximetry: application in the pediatric and neonatal critical care unit. AB - The use of pulse oximetry in the pediatric and neonatal intensive care units has grown tremendously in recent years. Opinions about this growth are divergent. Arriving at a generalized statement about the accuracy of pulse oximeters is difficult, but it has generally been found to be acceptably accurate in most patient populations under most conditions. However, there are limitations to its application. Pulse oximetry accuracy can be adversely affected by elevated levels of certain abnormal hemoglobin varieties as well as motion artifact and low peripheral perfusion. Some authors suggest a caveat against the use of pulse oximetry to prevent hyperoxemia in the neonatal population, whereas others suggest it is an important advancement. The affect of the use of pulse oximetry on respiratory morbidity and mortality has not been established, and suggestions that all mechanically ventilated patients should be continuously monitored are unsubstantiated. PMID- 2206735 TI - Extracorporeal membrane oxygenation: current use and future directions. AB - Extracorporeal membrane oxygenation (ECMO) is the process of using prolonged cardiopulmonary bypass to support patients with reversible respiratory and/or cardiac failure who are refractory to maximal conventional therapy. This process has been used extensively for critically ill neonates, with encouraging results. The use of ECMO in the pediatric population has been limited but is increasing. The history, mechanics, and current applications of ECMO are discussed in this article. Critical care nursing management of the pediatric or neonatal ECMO patient focuses on optimizing recovery of the pulmonary and/or cardiac system while preventing complications. A case study of a pediatric ECMO patient is presented which illustrates the complex nursing care issues related to use of this intervention. Future directions for ECMO are addressed. PMID- 2206736 TI - Preparing the family for home tracheotomy care. AB - Children with tracheotomy tubes are frequently cared for by nurses in critical care settings, as well as on general patient care units. These children require tracheotomies for a variety of reasons and often are ready to be discharged before they are ready to be decannulated. As a result, many children are cared for at home by their parents, other family members, or other care givers. Discharging a child home with a tracheotomy is a process that involves many people. The staff nurse plays a valuable role in providing education and support to the child and family. After discharge, otolaryngology nurse-clinicians provide some of the support and continuing education the families may need, while parents and school personnel assist the families with support in normalizing their lives and meeting the developmental needs of the child. PMID- 2206737 TI - Modes of ventilatory support and weaning parameters in children. AB - Pediatric respiratory therapy management has become increasingly complex. Mechanical ventilation has become a mainstay in neonatal and pediatric intensive care units. Thorough knowledge of the modes of ventilatory support and criteria for weaning are essential for the critical care nurse to anticipate patient needs. Ventilatory support is initiated when a patient exhibits respiratory failure. For whatever reason, the respiratory system cannot meet the metabolic demands for oxygenation and carbon dioxide (CO2) elimination. Indications for mechanical ventilation in children include marked hypoxia, hypercapnea, peripheral airway obstruction, chest wall deformities, and central nervous system abnormalities. Nurses caring for these children must possess adequate knowledge of the underlying disease process as well as normal respiratory physiology and technical features of ventilators. Nursing strategies can then be directed toward weaning children from the mechanical ventilatory support. PMID- 2206738 TI - Respiratory care in neonates. PMID- 2206739 TI - Embryologic and physiologic basis of neonatal respiration. AB - Development of the respiratory system requires the integration of anatomic, physiologic, and biochemical factors. This process is described from 5 weeks gestation until establishment of respirations after birth. PMID- 2206740 TI - Assessment of the neonatal respiratory system. AB - The nursing process related to alteration in respiratory status provides a framework to review information about neonatal respiratory assessment. The information includes definitions of terms used to document nursing observations. Risk factors affecting an alteration in respiratory status are outlined and diseases associated with respiratory dysfunction, many unique to the neonate, are discussed including the pathophysiology and defining characteristics. Nursing diagnoses are briefly stated. Presentation of a case study demonstrates the nursing interventions based on on the assessments made on the infant with progressing respiratory distress syndrome (RDS). An evaluation is made of the effect of nursing assessment on changing an infant's respiratory status. Keys to accurate nursing assessment of neonatal respiratory status are observation, recognition of contributory disease processes, and implementation and evaluation of appropriate nursing interventions. PMID- 2206741 TI - Noninvasive monitoring of the neonatal respiratory system. AB - The development and use of a large variety of nonivasive respiratory monitors have provided the neonatal intensive care unit clinician with invaluable tools for continuous monitoring. Thorough understanding of how each monitor functions, what it measures, and factors that contribute to monitor errors and injuries is vital for appropriate use of this technology and for proper interpretation of monitor values. On-going patient assessment and a good understanding of physiologic principles affecting respiratory status and monitoring also are imperative to interpreting monitor values. Noninvasive monitors have raised a controversy about home use of monitors to prevent sudden infant death syndrome--a review of National Institute of Health recommendations is helpful when cardiorespiratory monitoring is an issue. Family teaching and support are beneficial for discharge planning. PMID- 2206742 TI - On the horizon: surfactant replacement therapy. AB - During the past decade, significant advances in the treatment of neonatal respiratory distress syndrome (RDS) have been directly attributable to the emergence of surfactant replacement therapy. Using a variety of surfactant preparations, clinical trials have been accomplished in a number of centers on large numbers of infants. These clinical trials showed that there were applications of surfactant replacement both in the prevention mode, early in life, and in the rescue mode, once RDS is diagnosed. There were no evident adverse effects on the infants, and there was significant reduction in mortality and severity of disease in the treated infants. Currently, a large number of neonatal intensive care units are enrolling infants in treatment investigational drug (IND) protocols as defined by the Food and Drug Administration (FDA) while the new drug applications are pending. Surfactant replacement therapy has numerous implications for neonatal nurses and will be part of all neonatal nursing skills in the near future. PMID- 2206744 TI - Psychological aspects of pregnancy. PMID- 2206743 TI - High-frequency ventilation and extracorporeal membrane oxygenation. AB - Dramatic improvement in morbidity and mortality associated with neonatal respiratory failure has evolved over the last 30 years. Favorable survival statistics can be directly related to the institution and refinement of assisted ventilation techniques. Short- and long-term pulmonary complications continue to be of major concern. New ways to support the neonate in respiratory failure are being investigated. Concentrated efforts are being undertaken to find ways to safely and effectively treat these infants while decreasing the morbidity associated with therapy. Two such therapies, both experimental and controversial, which are gaining widespread recognition, are high-frequency ventilation (HFV) and extracorporeal membrane oxygenation (ECMO). PMID- 2206745 TI - A framework for the psychological aspects of pregnancy. AB - During pregnancy, a woman reformulates and alters her existing identity to develop a maternal identity and role. A framework for this process of maternal identity formation is described. Key aspects of the framework are the self-system (ideal, actual, and body image selves) and the maternal tasks of pregnancy. Nursing diagnoses, goals, and interventions are identified related to the self system and tasks of pregnancy. Clinical application of the framework can provide nurses with assurance that the psychological aspects of pregnancy are addressed when planning, implementing, and evaluating the care of prenatal clients. PMID- 2206746 TI - Anxiety and stress in pregnancy: significance and nursing assessment. AB - This article explores the significance of research on prenatal anxiety and stress for application to clinical nursing practice. The focus will be on assessment of the gravid woman's anxiety levels and coping skills. An introduction presenting a paradigm of the transitional and paradoxical changes of pregnancy precedes a discussion of the nature and sources of anxiety in pregnancy and its effects on maternal/fetal health outcomes. The cumulative effects of multiple sources of anxiety and the relevance of early state anxiety and prenatal personality dimensions, such as maternal role identification and conjugal relationships, to health outcomes also are discussed. Methods for stress reduction and recommendations for future multidisciplinary and multivariate research projects conclude the article. PMID- 2206748 TI - Binding-in: still a relevant concept? AB - Development of the maternal-fetal relationship was described by Rubin as an intimate "binding-in process." Recent technological advances enabled health care providers to observe, study, diagnose, and treat unborn children and led some to reconsider the relevance of the binding-in concept. Research has focused on prenatal attachment or bonding, maternal characteristics that influence prenatal attachment/bonding, and interventions to promote it. Before binding-in is dismissed as irrelevant, assessment of the prenatal attachment research, consideration of the impact of these ideas on pregnant women and their families, and the implications for maternity nurses must be examined. PMID- 2206749 TI - Stress, social support, and self-esteem during pregnancy. AB - The relationship between stress, social support, and self-esteem during pregnancy is explored. The effects of high stress and low social support and low self esteem on pregnancy outcomes are described and illustrated with a case example. Examples of nursing interventions aimed at reducing stress and enhancing social support and self-esteem during pregnancy are provided. PMID- 2206747 TI - Uncertainty in pregnancy. AB - Although often unrecognized by care providers, uncertainty during pregnancy is universally experienced. The antecedents to uncertainty are exemplified with qualitative data from interviews with pregnant women. The following antecedents are discussed: (1) symptom patterns; (2) event familiarity; (3) event congruence; (4) cognitive capacity; (5) structure providers; and (6) credible authority. The importance of exploring uncertainty during pregnancy stems from the relationship between the stress associated with uncertainty and perinatal complications. Negative caregiver reactions to uncertainty that can intensify stress include ignorance, intolerance, and indifference. Suggestions for nursing assessments and interventions during prenatal care are provided. PMID- 2206750 TI - First-time expectant fatherhood: nursing care considerations. AB - The transition to parenthood is a major life event for a man, yet, for the most part, the father remains a stranger, overshadowed by the mother. A brief summary of the author's research findings related to the male experience of expectant and new fatherhood is presented and utilized as the basis for discussion of nursing actions during the antepartum period to support and promote the male transition to parenthood. PMID- 2206752 TI - Working during pregnancy: psychological stressor or asset? AB - Nearly half of women continue working during at least part of pregnancy. Health promotion for the pregnant client includes a focus on the impact of work on her health and the health of her fetus. Concerns about environmental hazards in the workplace, workplace stressors, and a non-supportive work environment contribute to the psychological vulnerability of the pregnant worker. However, working can also provide the pregnant woman with important health resources. Because of the potential of work during pregnancy to be both a stressor and a benefit, individualized assessment and counseling for each pregnant woman is indicated. PMID- 2206751 TI - Psychological aspects of second pregnancy. AB - Major psychological characteristics of the second pregnancy experience are described, including maternal tasks and sources of anxiety for secundigravidas, as a basis for improving care to expanding families. Clinical implications are suggested that meet the special needs of second-time mothers regarding time limitations to meet multiple demands, family relationship changes, and concerns about maternal health and fatigue. Strategies for enhancing care involve using childbirth and sibling classes, modifying health care and information from primary care providers, mobilizing supportive services and resources, and influencing policies to meet maternal and family needs. PMID- 2206754 TI - Psychosocial implications of pregnancy after infertility. AB - Couples who become pregnant after being infertile experience profound psychosocial changes related to the "identity shift" that they must make from infertility to pregnancy. They often straddle the two worlds of infertility and fertility, not feeling completely a part of either world. Nurses play a key role in counseling, educating, and supporting these individuals and couples during the antepartum, intrapartum, and postpartum periods. This article discusses current knowledge about pregnancy after infertility and the implications for nursing practice. PMID- 2206753 TI - Psychosocial aspects of antepartum hospitalization. AB - High-risk pregnant women who undergo antepartum hospitalization experience significant stress. Nurses play an important role in helping these pregnant women adapt to their high-risk status and cope effectively with hospitalization. This article identifies the stressors imposed by antepartum hospitalization and discusses nursing interventions to reduce the impact of those stressors. PMID- 2206755 TI - Postpartum depression. PMID- 2206756 TI - An overview of postpartum psychiatric disorders. AB - The purpose of this review is to highlight reasons why increased attention should be paid to the prevention and treatment of psychiatric disorders at childbirth. The two main psychiatric disorders that are associated with childbirth--postnatal depression and postpartum psychosis--are reviewed, together with a discussion of the maternity blues. An overview of each condition is presented, identifying incidence rates, clinical manifestations, and appropriate treatment approaches. Recommendations are made for coordination and development of services as a means to achieve prevention and treatment of postpartum psychiatric disorders. PMID- 2206757 TI - Prediction of postpartum depression. AB - This article briefly reviews definitions, etiology, and cultural aspects of postpartum depression. Studies attempting to predict postpartum depression are examined, and a summary of risk factors is given. The importance of educating all pregnant women about postpartum depression is stressed, and sample patient education information is presented. PMID- 2206758 TI - Baby blues: identification and intervention. AB - Transitory postpartum depressive syndrome or baby blues affects up to 80% of all newly delivered women. Baby Blues is so common it may be considered normal. While one of the more mild forms of depression after child birth, it can still be disruptive to the family unit. Both physiological and psychosocial factors contribute to the syndrome. Appropriate nursing assessment and intervention throughout the childbearing cycle can be very beneficial in helping families to understand and cope with the problem, as well as help prevent more serious depressive syndromes. PMID- 2206759 TI - Postpartum depression in the breastfeeding mother. AB - This article reviews the literature discussing postpartum depression and lactation, noting that most studies are plagued by definitional problems relating to feeding group purity and lack of clarity regarding the definition of depression. The implications for nurses when they are asked to care for a breastfeeding mother with postpartum depression are identified and discussed, with special attention paid to the importance of maintaining and/or supporting the maternal role. Decision-making relating to interruption or continuation of breastfeeding as a result of psychotropic drug therapy is discussed. PMID- 2206760 TI - Reaching out: depression after delivery support group network. AB - Women have suffered from postpartum depression for years without any support. Fortunately, both the public and professional sectors have become aware of postpartum illnesses, and efforts have begun to provide mothers with effective forms of intervention. This article describes the value of support groups, particularly, Depression After Delivery. Suggestions for nurse involvement are offered. PMID- 2206761 TI - A select psychiatric mother and baby unit in Britain: implications for care in the United States. AB - Severe psychiatric disturbances that arise during the postpartum period have serious implications for the optimal development of the mother-infant relationship. The treatment approach of psychiatric admission in the postpartum period raises the issue of whether to admit the mother together with her infant or to separate the two. This article describes the nursing care on a select Psychiatric Mother and Baby Unit in Britain utilizing the nursing process. Implications for inpatient management of postpartum disorders in the United States are presented giving special consideration to the significance of the mother-infant dyad. PMID- 2206762 TI - Postpartum psychosis: a family's perspective. AB - One couple's experience of a postpartum mental illness that led to the tragedy of infanticide is described. A case background is presented to highlight significant objective data relevant to a previous pregnancy. Individual recommendations are made to the health care profession on how to better intervene with families experiencing a postpartum psychiatric illness. Nursing implications are discussed. PMID- 2206763 TI - Recovery systolic blood pressure response after treadmill exercise procedures. Evidence against its usefulness in detecting coronary artery disease. AB - We compared the response of the systolic blood pressure (SBP) recovery ratio (obtained by dividing the SBP recovery values by the peak exercise values) during a treadmill exercise test in patients with chest pain and an angiographically normal coronary tree (n = 18) (C group), one or more greater than or equal to 70% stenosed major coronary vessel and normal resting ejection fraction (n = 26) (CAD group) or depressed left ventricular function (ejection fraction less than 40%) (n = 15) (CAD DYS group). The mean values of SBP recovery ratios were, in the three groups: 0.93 +/- 0.07, 0.97 +/- 0.07, 0.95 +/- 0.09, respectively, at the 1st min and 0.83 +/- 0.08, 0.88 +/- 0.09, 0.86 +/- 0.08, at the 3rd min. There are no significant differences in the CAD or CAD DYS group versus the C group, because of large overlapping of points in the plot. The post-exercise SBP response during treadmill procedures cannot provide the opportunity for differentiation of CAD patients with or without left ventricular dysfunction at rest from subjects with chest pain and normal coronary tree, while upright bicycle exercise, as we previously observed, can. PMID- 2206765 TI - Increased prevalence of intestinal metaplasia in the gastric mucosa of the elderly: clinical implications. AB - Evidence which suggests a close relationship between intestinal-type gastric carcinoma (IGC) and intestinal metaplasia (IM) associated with chronic atrophic gastritis (CAG) has accumulated in the literature. The aim of this study has been to analyze retrospectively the prevalence of IM in patients with bioptically proven chronic gastritis, as well as its age-specific distribution. A series of 230 patients, comprising 162 cases of CAG with IM (70.5%) and 68 cases of gastritis without IM (29.5%-57 superficial type, 11 CAG) was reviewed. All patients underwent upper gastrointestinal endoscopy one or more times, during which multiple biopsies were taken from the gastric mucosa. Moreover, patients were divided into two age-groups: over and under 65 years old. Three features were also investigated: location, endoscopic appearance and clinical manifestations. In agreement with other Authors, our findings showed: 1) predominance of the antral location (B-type gastritis); 2) a close relationship between prevalence of IM and increasing age, with an upward age-related trend. A statistically significant difference was noted between patients with IM and those without the lesion, emerging in the VII decade, with a further rise in the succeeding decade. In line with the literature, these findings emphasize the importance of endoscopic-bioptic follow-up, which takes on even greater significance in elderly patients, in whom an increased incidence of IGC has been reported. PMID- 2206764 TI - 24-hour profiles of blood pressure and heart rate in Cushing's syndrome. Evidence for differential control of cardiovascular variables by glucocorticoids. AB - We monitored the circadian profile of cortisol, systolic and diastolic blood pressure (SBP and DBP), heart rate (HR) in 33 normotensive subjects aged 20-40 years, 20 normotensive subjects aged 40-60, 32 patients with essential hypertension and 13 patients with Cushing's syndrome (6 pituitary adenomas, 5 adrenal adenomas and 2 adrenal carcinomas). All controls and patients underwent serial blood drawings at 4-h intervals during the 24-h cycle. BP and HR were recorded every 30 min by an automatic, room-restricted instrument. Data were analyzed by conventional statistics and by chronobiological procedures (cosinor rhythmometry) to quantify rhythm parameters such as the MESOR (rhythm-adjusted average), amplitude (difference between maximum and MESOR) and acrophase (timing of the crest of the rhythm). Both the control and essential hypertensive subjects showed a BP and HR circadian profile characterized by a peak in the early afternoon and a clear nocturnal fall (rhythm detection: p less than 0.001). The chronobiological analysis did not reveal any significant difference between healthy young and aged subjects. BP rhythmicity was disrupted in patients affected by Cushing's syndrome, whereas the 24-h oscillation of HR was preserved (p less than 0.001). Patients with pituitary-dependent Cushing's syndrome had higher BP levels than adrenal-dependent subjects (p less than 0.001). Our data are compatible with the view that glucocorticoids are involved in the control of BP circadian rhythm, whereas HR is not under their control. PMID- 2206766 TI - [Myxedema coma]. AB - Myxedema coma, an extreme expression of hypothyroidism, represents a medical emergency with high mortality. Hypothermia and cerebro-vascular accidents should be taken into account for correct differential diagnosis. The treatment of myxedema coma is based on prevention of the precipitating factors and on the administration of generous doses of L-thyroxine and/or triiodothyronine, associated with steroids and drugs for respiratory and cardio-vascular complications. PMID- 2206768 TI - Influence of age on left ventricular performance during exercise in normal Japanese subject: assessment by radionuclide ventriculography. AB - To assess the effects of age on left ventricular performance, multistage supine ergometer exercise radionuclide ventriculography (RNV) was performed in 92 normal subjects. The subjects ranged in age from 24 to 86 years and were free of cardiopulmonary disease and diabetes. Age-related changes in exercise duration, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), cardiac output (CO) left ventricular ejection fraction (LVEF), left ventricular dv/dt, systolic and diastolic time indexes of dv/dt, and peak systolic pressure/left ventricular end-systolic volume (PSP/LVESV) were analyzed at rest and during the peak exercise stage. Age-related decrease in LVEDV and peak diastolic dv/dt were significant at rest. The time indexes of ECG R to peak systolic dv/dt and time of end-systole to peak diastolic dv/dt also were prolonged with age. Both maximum heart rate and exercise duration were shown to decline with age. No age-related difference was observed in LVESV, LVEF or PSP/LVESV either at rest or during exercise. However, the change of LVEF and LVESV during exercise was less in subjects aged 60 or more. These results indicate decreased left ventricular function during exercise in elderly subjects. PMID- 2206767 TI - Visualization of the bone/bone marrow of lower extremities in Ga-67 whole-body images. AB - Patients whose Ga-67 whole-body images showed increased uptake by the bone/bone marrow of the lower extremities were selected and classified into three types according to the extent and the grade of the visualization. These types were then compared with their serum iron levels, iron-binding capacities, and the results of several other serum biochemical tests. Of 374 consecutive whole body 72-hr images reviewed, 59 (15.8%) showed increased uptake of the tracer by the bone/bone marrow of the lower extremities. The three classified types were as follows: type T--visualization of both tibiae and femurs; type S--strong visualization of the femurs; and type W--weak visualization of the femurs. The serum iron concentration was significantly high in type T and low in type S. In conclusion, the pattern of Ga-67 uptake by the bone/bone marrow of the lower extremities fairly closely reflects the status of iron metabolism. PMID- 2206769 TI - Problems of [S-methyl-11C]-L-methionine as a protein synthesis marker in the pancreas. AB - To evaluate the possibility of [S-methyl-11C]-L-methionine as a protein synthesis marker in the pancreas, the effect of various labeling positions in the accumulation and metabolism of 14C-labeled L-methionines (S-methyl-14C, 1-14C and 3,4-14C) was studied. In mouse biodistribution studies, the methionines showed differing patterns of labeling position-dependent pancreatic accumulation. In the case of [S-methyl-14C]-L-methionine, protein-incorporation and methyl transformation equally served as retention mechanisms in the pancreas, indicating [S-methyl-11C]-L-methionine's unsuitability as a pancreatic protein synthesis marker. For such purposes, [1-11C]-L-methionine is considered more suitable. PMID- 2206771 TI - The pathophysiology of the pro-inflammatory cytokines. PMID- 2206770 TI - Gallium-67 uptake in fibrous dysplasia of the bone. AB - In a 43-year-old woman with fibrous dysplasia of the ribs and facial bone and in a 40-year-old man with fibrous dysplasia of the facial bone, there were considerable increases in the uptake of Tc-99m methylenediphosphonate (Tc-99m MDP) and Gallium-67 citrate. Fibrous dysplasia should be added to differential diagnosis of high Gallium-67 citrate uptake in the bone lesions. PMID- 2206773 TI - Peri-operative immunotherapy with OK-432. AB - Pre- and postoperative intradermal administration of OK-432 enhanced the SU-PS skin reaction in patients with gastric cancer, but failed to prevent a fall in the NK activity induced by the operation. The change in NK activity was not associated with a change in the proportion of Leu 7-positive cells, but was related to Leu 11a-positive cells. Intradermal injection of OK-432 increased the proportion of Leu 7-positive cells in the patients in whom they accounted for less than 20% of lymphocyte population. The case was the same with Leu 11a positive cells. Intravenous injection of OK-432 tended to increase suppressor inducer T cells (CD4+2HA+ cells), B cells and Leu 7-positive cells. Particularly, the proportions of OK-M1-positive cells and MHC class II antigen-positive cells increased in all patients. Immunotherapy with OK-432 given intravenously at a dose of 0.1 KE appeared to be safe because no side effects were essentially observed. PMID- 2206772 TI - Augmentation of various immune reactivities of tumor-bearing hosts with an extract of Cordyceps sinensis. AB - In order to enhance general reactivity of immune system in the tumor-bearing host, we employed extract of Cordyceps sinensis (CSE) as a biological response modifier. Cordyceps sinensis is an interesting material produced by a kind of mushroom parasitic to larval moths and was used to hasten recovery from exhaustion in ancient China. In this experiment, C57BL/6 mice implanted subcutaneously with syngeneic EL-4 lymphoma cells were employed as the host. Oral administration of the extract leads to a reduction of tumor size and prolongation of the host survival time. As judged by plaque-forming cells against T-dependent (sheep erythrocytes) and T-independent (bacterial lipopolysaccharide) antigens, CSE showed to augment the antibody responses. As for the activities of peritoneal macrophages, chemotaxis was dramatically depressed within a few days after EL-4 transplantation up to the end of life, but treatment with CSE at -14, -7, -4, +4, +7 and +10 days after the tumor transplantation augmented the activity about four times stronger than that of control. Phagocytic activity of macrophages was also decreased in tumor-bearing mice treated with cyclophosphamide (100 mg/kg) 3 and 5 days after tumor transplantation. But administration of CSE restored the activity to more than the normal level. The overall efficacy of CSE was tested with protective activity against systemic infection by Salmonella enteritides. The tumor-bearing mice receiving this medicine lived significantly longer than any other groups without CSE. PMID- 2206774 TI - Orally administered streptococcal preparation, OK-432 augments the antitumor immunity of patients with gastric or colorectal cancer. AB - A streptococcal preparation, OK-432, was orally administered at a dose of 5 KE to patients with gastric or colorectal cancer for 7-14 days before their operations, and its immunomodulatory effects on peripheral blood lymphocytes (PBL), regional node lymphocytes (RNL) and tumor infiltrating lymphocytes (TIL) were assessed. The group treated with OK-432 included 8 gastric and 6 colorectal cancer patients, and the control group included 8 gastric and 8 colorectal cancer patients. The NK cell activity of PBL was significantly augmented by the oral administration of OK-432, and the proportions of Leu 7+ and Leu 11+ cells in PBL also increased. The responses of PBL and TIL to autologous tumor extracts in the presence of interleukin-2 were enhanced after the oral administration of OK-432. The proportion of OKT8+ cells in PBL increased after treatment with oral OK-432, whereas the proportion in RNL significantly decreased. These results indicate that oral OK-432 affects NK and T cells and may augment the antitumor immunity of patients with gastrointestinal cancer. PMID- 2206775 TI - Changes in immunological parameters in lung cancer patients undergoing immunotherapy with streptococcal preparation OK-432. AB - We have studied the immunological status of patients treated with streptococcal preparation OK-432. Two KE of OK-432 was injected intramuscularly once every week for more than three years unless the patients died. The natural killer (NK) activity in those patients who underwent curative surgery for lung cancer and had no sign of recurrence was significantly increased (P less than 0.01) during the OK-432 treatment. However, the NK activity in the patients who had persistent disease (non-resected cases, incompletely resected cases or recurrent cases) was not significantly increased in comparison with that before the immunotherapy. Also, in the cases with no clinical symptoms of recurrence, both the lymphoblastogenetic reactions to the mitogens and the IL-2 production were significantly enhanced (P less than 0.01) during the administration of OK-432. Reactions in the SU-PS (polysaccharide taken from the cell-wall fraction of the Streptococcus pyogenes SU strain and containing 7.2% of protein) skin-test appeared to significantly correlate with the immunological status of the patients under OK-432 therapy, but the PHA and PPD skin reactions showed no definitive enhancement. The survival rate of the patients whose SU-PS skin tests were positive during the OK-432 immunotherapy was significantly higher (P less than 0.01) than that of the patients with negative reactions. PMID- 2206776 TI - TNF: a brief review with emphasis on its antitumor activity. PMID- 2206777 TI - Modulation of EGF receptor expression by differentiating agents in human colon carcinoma cell lines. AB - The existence of an autocrine loop for self-stimulation of growth in malignant cells has been proposed for transforming growth factor-alpha (TGF alpha) and its receptor, the epidermal growth factor (EGF) receptor, in a variety of malignant cell types. Expression of both has been described in colon carcinoma. In order to investigate whether there is a correlation between TGF alpha and EGF receptor mRNA expression and differentiation, we studied the effects of differentiating agents on seven human colon carcinoma cell lines. All of the lines responded to the differentiating agents. In four of the seven lines there was increased EGF receptor mRNA two to five days after treatment with 2 mM sodium butyrate. In three of these lines TGF alpha mRNA and protein were also increased. In the one cell line treated with the differentiating agents DMF and DMSO, EGF receptor mRNA was also increased. [125I]-EGF binding to the cells was measured before and after treatment with butyrate. In two of three cell lines, increased EGF receptor mRNA was accompanied by a 2.4-fold increase in the number of binding sites per cell. In SW620 cells, no EGF receptor binding was detected before or after butyrate treatment. In the two cell lines in which butyrate increased EGF receptor binding, simultaneous treatment with EGF did not enhance growth. These data demonstrate increased expression of the TGF alpha/EGF receptor system after differentiation of colon carcinoma cell lines and suggest that their expression may be characteristic of a differentiated phenotype. PMID- 2206779 TI - Effect of lactose derivatives on metastatic potential of B16 melanoma cells. AB - The effects of various sugars and sugar derivatives on lung colonization (i.e., metastatic deposition) of the highly metastatic BL6 clone of B16 mouse melanoma cells in syngeneic mice were studied, based on the assumption that carbohydrate structures, particularly those with a Gal terminus, play a crucial role in defining the metastatic potential of B16 cells. After incubation with sugar compounds (usually at 0.1 M concentration), tumor cells were injected via the tail vein into 8-week old female mice. Mice were sacrificed after 18-21 days, and tumor cell colonies in lung were counted under a dissecting microscope. Only methyl beta-D-lactoside and lacto-N-tetraose caused significant reduction (35-45% and 36%, respectively) of metastatic deposition compared to controls. Methyl beta D-lactoside did not exhibit a growth inhibitory effect on BL6 tumor cells, as determined by several methods: in vitro [3H]thymidine incorporation assay, in vitro plating in RPMI-1640 medium culture under physiological conditions followed by cell counting, and in vivo subcutaneous inoculation of age-matched C57/BL mice followed by tumor measurement. These results indicate that the inhibitory effect of methyl beta-D-lactoside on tumor deposition was not related to its effect on tumor cell growth. PMID- 2206778 TI - Preferential selection during therapy in vivo by edatrexate compared to methotrexate of resistant L1210 cell variants with decreased folylpolyglutamate synthetase activity. AB - Acquired resistance of the L1210 leukemia in mice developed with less rapidity during therapy with edatrexate (10-ethyl-10-deazaaminopterin, EDX) than with MTX. Since this was explained only partially by the somewhat greater antitumor activity of EDX, this result may also reflect a difference in biochemical phenotypes selected in each case. Among 20 sublines selected for resistance to MTX, a reduction in influx, an elevation of DHFR, and a reduction of DHFR inhibition by MTX were all delineated. Among 14 sublines selected for resistance to EDX, both a reduction in influx and an elevation in level of DHFR were also commonly found. In addition, however, 7 of 14 EDX-resistant sublines exhibited a reduction in the level of folylpolyglutamate synthetase (FPGS) activity. Clonal derivatives of these 7 EDX-resistant cell lines exhibited 2- to 28-fold reductions in FPGS activity and a commensurate reduction in [3H]-MTX polyglutamate formation in situ following exposure to [3H]-MTX during growth in mice. An analysis of the kinetics and relative substrate preferences for FPGS from variant and parental L1210 cells revealed that the various changes in FPGS activity were at the level of the Vmax rather than Km. These results derived from an in vivo tumor model provide further evidence for a role of FPGS as a determinant of cytotoxicity and acquired resistance to classical folate analogs. They also provide evidence in the same pharmacologic model for a manifestation of resistance to 4-aminofolates in vivo that involves all of the alterations of its primary target, transport, and metabolism that have ever been associated with acquired resistance in cell culture systems. PMID- 2206780 TI - Is homoeopathy a placebo? PMID- 2206781 TI - Platelet function tests in the assessment of antithrombotic agents. PMID- 2206782 TI - Dipyridamole alone or combined with low-dose acetylsalicylic acid inhibits platelet aggregation in human whole blood ex vivo. AB - 1. In a randomized, double-blind trial we compared the inhibition of the platelet vessel wall interactions in whole blood ex vivo. There were four groups of 24 healthy volunteers each of whom were treated orally for 3.5 days with either 200 mg dipyridamole (sustained release preparation), 25 mg acetylsalicylic acid, both drugs combined or placebo twice daily. 2. The mean area of all platelets/aggregates was reduced by 6.2% +/- 4.2% (+/- s.e. mean) by placebo (n = 23), 19.8% +/- 6.7% by dipyridamole (n = 22), 53.7% +/- 4.9% by acetylsalicylic acid (n = 23) and 71.4% +/- 3.7% by the combination of both drugs (n = 24), when compared with total inhibition of aggregation by EGTA. Thus, low-dose acetylsalicylic acid inhibited aggregation (P less than 0.001). 3. Dipyridamole reduced the size of platelet aggregates (P less than 0.01, two-fold analysis of variance). The reduction was correlated with the individual dipyridamole plasma levels (P less than 0.05, analysis of covariance). The subgroup of large and very large thrombi being formed was also reduced by dipyridamole (P less than 0.05). 4. This ex vivo study demonstrates that dipyridamole alone inhibits formation of thrombi on subendothelial matrix and enhances the inhibitory effect of low dose acetylsalicylic acid in this model of thrombosis. PMID- 2206783 TI - Enalapril and nifedipine in the treatment of mild to moderate essential hypertension: a 6 month comparison. AB - 1. In a double-blind, randomised, parallel group study, 128 patients with sitting diastolic blood pressure between 95 and 125 mm Hg (Phase V) after 2-4 weeks run in on placebo, received enalapril 10-40 mg once daily (65 patients) or nifedipine retard 10-40 mg twice daily (63 patients), utilising a double dummy technique. Dual target blood pressures were less than 150 mm Hg systolic and less than 90 mm Hg sitting diastolic. Inadequate responders had hydrochlorothiazide 12.5-50 mg once daily added. 2. The 3 h post-dose sitting blood pressures were lowered by 18/14 mm Hg (enalapril) and 20/14 mm Hg (nifedipine), but nifedipine gave greater standing reductions (16/13 mm Hg enalapril, 22/17 mm Hg nifedipine). The dual target blood pressures were achieved by 45% of those taking enalapril monotherapy and 43% of those taking nifedipine monotherapy. At the end of the hydrochlorothiazide phase the dual target pressures were achieved by 63% of the enalapril group and 56% of the nifedipine group. 3. Overall, 17 patients reported adverse events during the placebo run-in. During the active treatment-periods, 42 patients in the enalapril group experienced adverse events, as did 49 of those on nifedipine. Orthostatic effects were confined to those taking enalapril, whereas flushing/erythema, oedema and palpitations were more common in the nifedipine group. 4. Five patients in the enalapril and 14 in the nifedipine groups were withdrawn because of adverse events. One of those withdrawn on enalapril had angioneurotic oedema.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206785 TI - The effect of food on serum concentrations of metopimazine. AB - 1. Six healthy volunteers were given single oral doses of the antiemetic metopimazine (MPZ), starting with trial (a) 20 mg preprandially and followed by trial (b) 50 mg preprandially. In trials (c) and (d) the doses were similar to those in trials (a) and (b), but MPZ was given postprandially. To evaluate intra individual variation in serum concentrations, trial (a) was repeated three times in four of the volunteers (trial (e)). 2. Blood samples were drawn and the serum concentrations of MPZ and its acid metabolite (AMPZ) were measured by h.p.l.c. 3. There was no evidence of dose-dependent kinetics at the dose levels studied. 4. Median AUC values were 22.6, 16.2, 52.4 and 35.2 (trials (a), (b), (c) and (d), ng ml-1 h). Food intake decreased the serum concentrations of MPZ, suggesting that MPZ should be taken preprandially. PMID- 2206784 TI - Lack of effect of verapamil and isosorbide dinitrate on the hepatic clearance of indocyanine green in cirrhosis. AB - 1. Vasodilators are currently under investigation as possible therapeutic agents in the treatment of portal hypertension. Among them calcium-channel antagonists and organic nitrates have been of particular interest. Few and conflicting data, however, have been reported on their effect on liver function. 2. Twenty patients with biopsy-proven alcoholic cirrhosis were studied before and 25-35 min following the acute administration of 5 mg verapamil i.v. (eight patients) or 5 mg isosorbide dinitrate sublingually (12 patients). The plasma clearance of indocyanine green (ICG) and its intrinsic hepatic clearance were used as indices of liver function. Seven further patients were investigated before and after a placebo infusion according to the same methodology. 3. No significant change in ICG kinetics was found after verapamil or isosorbide dinitrate. PMID- 2206786 TI - Pharmacokinetics of the individual enantiomers of vigabatrin (gamma-vinyl GABA) in epileptic children. AB - 1. The pharmacokinetics of the enantiomers of vigabatrin were investigated after oral administration of a single 50 mg kg-1 dose of the racemate to two groups of six epileptic children (I: 5 months-2 years, II: 4-14 years). 2. The mean (+/- s.d.) values of maximum plasma concentration and area under the plasma concentration-time curve of the R(-) enantiomer were significantly higher than those of S(+) vigabatrin in both groups: R(-) Cmax: 21 +/- 6.6 (I)-41.3 +/- 13.9 (II) vs S(+) Cmax: 13.9 +/- 4.5 (I)-23.8 +/- 12.2 (II) mg l-1; R(-) AUC: 106 +/- 28.5 (I)-147 +/- 34 (II) vs S(+) AUC: 90.9 +/- 27.9 (I)-117 +/- 26 (II) mg l-1 h. In group I, the half-life of the R(-) isomer was significantly shorter than that of the S(+) isomer; in group II, the half-lives were comparable. 3. For the R(-) enantiomer the area under the curve, and the elimination half-life increased linearly with age. 4. During chronic administration (50 mg kg-1 vigabatrin racemate twice a day for 4 days), the morning trough plasma drug concentrations did not increase. PMID- 2206787 TI - Multiple-dose pharmacokinetics and in vitro antimalarial activity of dapsone plus pyrimethamine (Maloprim) in man. AB - 1. The multiple-dose kinetics of dapsone (DDS), its major metabolite monoacetyldapsone (MADDS) and pyrimethamine (PYR) were studied in six healthy adult male volunteers following weekly administration of Maloprim (100 mg DDS plus 12.5 mg PYR). 2. After the last maintenance dose of Maloprim, the following kinetic parameters (mean values) were determined for DDS and PYR, respectively: maximum plasma concentration (Cmax) = 1,134 and 116 ng ml-1; elimination half life (t1/2) = 23 and 105 h; plasma clearance (CL) = 37.6 and 15.9 ml h-1 kg-1 and apparent volume of distribution (Vss) = 1.20 and 2.29 l kg-1. The mean t1/2 of MADDS was 22 h. 3. The mean whole blood to plasma (B/P) and erythrocyte to plasma (E/P) concentration ratios for DDS were 1.04 and 1.09, respectively. MADDS had a B/P ratio of 0.69 and an E/P ratio of 0.33. The B/P and E/P ratios for PYR were 0.98 and 0.54, respectively. 4. The drug combination was assessed in vitro by measuring inhibition of re-invasion of two Plasmodium falciparum isolates grown in the presence of volunteers' sera. The chloroquine (CQ)- and PYR-sensitive FC 27 isolate was completely inhibited by the sera but the drug combination was ineffective against the CQ- and PYR-resistant K1 strain. The in vitro findings suggest that Maloprim may not be effective against strains of P. falciparum with a high level of resistance to pyrimethamine. PMID- 2206788 TI - The excretion of zopiclone into breast milk. AB - 1. The excretion of zopiclone into breast milk was studied in 12 lactating women in the early postpartum period following the oral administration of a single zopiclone tablet (7.5 mg). 2. The milk/plasma AUC ratio of zopiclone was 0.51 +/- 0.09 (mean +/- s.d.). Individual mean milk/plasma concentration ratios of zopiclone showed significant interindividual variation (range 0.41-0.70). 3. A comparison of pharmacokinetic parameters in the postpartum women with those reported previously in non-pregnant women, showed significantly higher Cmax values in the lactating mothers; tmax occurred later in milk than in maternal plasma. 4. Assuming a daily milk intake of 0.15 l kg-1 and 100% absorption the average infant dose of zopiclone in milk would be 1.4% of the weight adjusted dose ingested by the mother. PMID- 2206789 TI - Clinical experiences with a novel percutaneous amethocaine preparation: prevention of pain due to venepuncture in children. AB - 1. The efficacy and safety of a novel percutaneous anaesthetic preparation based on amethocaine has been investigated in the paediatric clinical environment. 2. There were 1241 recorded applications on a named patient basis made to patients from infant to age 16 years. Of these, 88.7% had satisfactory anaesthesia to venepuncture challenge, rising to approximately 90% when the infant group was excluded. 3. A 30 min application time was found to be adequate for reliable topical anaesthesia. 4. There were no serious adverse reactions to the preparation. Of the total 6.9% recorded reactions, 6.3% were of a mild, transient erythema later identified as due to the vasodilator action of the drug. 5. A total of 123 patients received more than one application of the preparation. There was no evidence of sensitisation on subsequent exposure to the preparation. 6. The short application time required was found to be advantageous to ward and clinic routines. PMID- 2206790 TI - Unimodal distribution of the metabolic ratio for debrisoquine in Cuna Amerindians of Panama. AB - 1. The metabolic oxidation of debrisoquine (DB) was studied in 89 non-related Cuna Amerindian subjects. 2. Means and standard deviations for urinary recoveries of the intact drug and its 4-hydroxy metabolite (4-HD) were: %DB: 6.8 +/- 4.5; %4 HD: 16.0 +/- 9.1; %sum: 22.8 +/- 12.0. The log10 metabolic ratios for DB (LMRDB) were distributed within a single mode of insignificant skewness (-0.01, P greater than 0.10), which was unimodal (log kernel density and maximum likelihood methods) and normal (chi 2 = 22.5; d.f. = 15; P greater than 0.09; power of the test greater than 80%). 3. Therefore, no poor metabolizers (95% C.I.: 0.1%, 5.2%) were detected in the population sample studied. PMID- 2206791 TI - In vitro metabolism of the biguanide antimalarials in human liver microsomes: evidence for a role of the mephenytoin hydroxylase (P450 MP) enzyme. AB - The metabolic activation of the arylbiguanide antimalarials proguanil (PG) and chlorproguanil (CPG) has been investigated in liver microsomes from three human livers. All three microsomal preparations activated the biguanides. The kinetic parameters for PG metabolism to cycloguanil (CG) were Km 21.8, 29.6 and 26.4 microM and Vmax 1.5, 5.9, and 8.2 pmol min-1 mg-1. The values for CPG conversion to chlorcycloguanil (CCG) were Km 12.9, 19.7 and 26.1 microM and Vmax 5.7, 4.8 and 3.6 pmol min-1 mg-1. The metabolic activation of both biguanides was competitively inhibited by the anticonvulsant mephenytoin. Sparteine and tolbutamide had no effect on biguanide metabolism. These data suggest an involvement of the mephenytoin hydroxylase enzyme, which exhibits a genetic polymorphism in man, in the metabolic activation of the biguanide antimalarials. PMID- 2206792 TI - Changes in indocyanine green kinetics after the administration of enalapril to healthy subjects. AB - Enalapril maleate, an angiotensin converting enzyme inhibitor, is a vasodilator liable to modify regional blood flow. The effects of an oral dose of 40 mg enalapril maleate on indocyanine green (ICG) kinetics were assessed in nine healthy subjects. At 4 h after the administration of the drug, a 35% decrease in ICG clearance was observed (P less than 0.01) associated with a 23% decrease in its volume of distribution (P less than 0.02). The half-life of ICG was not altered significantly by enalapril. These results suggest that the administration of enalapril maleate to healthy subjects may reduce apparent liver plasma flow and plasma volume, as a consequence of the pooling of blood in the hepatosplanchnic area. PMID- 2206793 TI - Poor hydroxylator phenotypes of debrisoquine and S-mephenytoin are not over represented in a group of patients with Parkinson's disease. PMID- 2206794 TI - Proceedings of the British Pharmacological Society, British Pharmacology Section. 18-20 April 1990, Sheffield. Abstracts. PMID- 2206796 TI - Clinical and radiographic features of ankylosing spondylitis. PMID- 2206795 TI - Local metabolic responses to cerebral ischemia. AB - The brain is a highly differentiated organ, exhibiting a variety of local metabolic and hemodynamic responses to ischemia. Several analytical strategies are useful in characterizing these abnormalities: these include the direct assay of tissue metabolites; topographic methods for depicting regional patterns of NADH, ATP, glucose, lactate, and pH; in vivo spectroscopic methods for analyzing mitochondrial redox state over time; autoradiographic approaches to quantitation of local glucose utilization, blood flow, protein synthesis, and pH; and the noninvasive methods of positron emission tomography and NMR spectroscopy, which are applicable as well to human studies. In focal ischemia, "core" regions of severe blood-flow reductions progress to irreversible injury, while the adjacent "penumbral" zone appears to represent an unstable region threatened with possible injury yet potentially amenable to therapeutic intervention. Glucose utilization in focal ischemia is remarkable for its local heterogeneity and, in the postischemic state, tends to be predictive of local tissue injury. The selective vulnerability of particular brain regions to injury following global ischemia has now been extensively correlated with alterations of local metabolism and hemodynamics. Hyperglycemia is generally deleterious to neuronal survival in ischemia--an effect mediated via tissue lactacidosis. Small differences in brain temperature also profoundly influence ischemic outcome. Areas remote from an ischemic focus may also show metabolic and functional abnormalities--so-called "diaschisis," which may be transneuronally and/or humorally mediated. Multiple neurotransmitters are released during ischemia and interact to influence tissue injury. Regional postischemic hypoperfusion may also influence outcome. PMID- 2206798 TI - Psoriatic arthritis. AB - Psoriatic arthritis is a common form of arthritis. It is recognized that there is a subset of patients who have a severe, disabling form of the disease, and that patients need to be treated earlier if a good outcome is to occur. The pathogenesis of psoriatic arthritis is still unclear, but the "experiment of nature" provided by the HIV infection may help further outline the causative mechanisms. Newer modalities of therapy are being investigated. PMID- 2206797 TI - Clinical and radiographic features of Reiter's syndrome and inflammatory bowel disease related to arthritis. PMID- 2206799 TI - Cardiac, ocular, and renal manifestations of seronegative spondyloarthropathies. PMID- 2206801 TI - Medical and surgical treatment of seronegative spondyloarthropathy. PMID- 2206800 TI - Immunology, genetics, and animal models of the spondyloarthropathies. PMID- 2206802 TI - Bacterial arthritis and osteitis in adults. PMID- 2206803 TI - Septic arthritis and osteomyelitis in children. PMID- 2206804 TI - Spirochetal arthritis, including Lyme disease. PMID- 2206805 TI - Infection complicating orthopedic procedures and arthroplasties. PMID- 2206806 TI - HIV- and AIDS-related musculoskeletal problems. PMID- 2206807 TI - Infection as a trigger to connective tissue disease. PMID- 2206808 TI - Pathogenic paraproteins: gammopathies and cryoglobulinemia. PMID- 2206809 TI - Complement deficiencies and abnormalities of the complement system in systemic lupus erythematosus and related disorders. PMID- 2206810 TI - The seronegative spondyloarthropathies. PMID- 2206811 TI - Infectious arthritis and immune dysfunction. PMID- 2206812 TI - Mammographic screening for breast cancer: recall rates using two views compared with the oblique view alone. AB - Six thousand and eighty women aged 40 to 64 years were screened for breast cancer by single oblique view mammography and 908 (14.9 per cent) were recalled for further examinations. It was estimated that the use of two-view mammography for initial screening would have resulted in a fall of the number of women recalled to 581 (9.5 per cent). More recently, with better equipment and the routine use of a moving grid, the recall rate at initial singleview screening in women over the age of 50 has fallen to the region of 10 per cent. The place of two-view screening is being evaluated in conjunction with grid films and, should a similar proportional fall in recall rates be gained by the addition of a second view, there may well be a place for two-view screening in this situation too. PMID- 2206814 TI - An open multicentre study of the efficacy and safety of a single dose of fluconazole 150 mg in the treatment of vaginal candidiasis in general practice. AB - The efficacy and tolerability of fluconazole given as a single oral dose of 150 mg were assessed in 1,017 patients in general practice presenting with signs and symptoms of vaginal candidiasis. At the review visit 7-14 days after treatment, about 95 per cent of patients reported being either cured or improved. High vaginal swabs taken from 43 patients out of 50 who failed following treatment revealed Candida albicans in 17 (1.8 per cent). Efficacy in patients with predisposing factors (oral contraceptives, antibiotics and recurrent vaginal candidiasis - four episodes or more in previous year) was not significantly different from that in those without these factors. Of patients who had received previous intravaginal therapy for vaginal candidiasis, 88 per cent preferred fluconazole, 10 per cent previous therapy and two per cent had no preference. Investigators assessed efficacy after fluconazole as excellent or good in 91 per cent and tolerability as excellent or good in 91 per cent of patients. Significant adverse effects were reported in less than one per cent of patients. PMID- 2206813 TI - Efficacy of ceftizoxime in the treatment of uncomplicated gonorrhoea: comparison with amoxycillin. AB - Four centres contributed a total of 466 patients to a study comparing the efficacy of oral amoxycillin with that of probenecid and intramuscular ceftizoxime. Both treatments were equally efficacious, except in the small number of penicillinase-producing Neisseria gonorrhoeae patients, all of whom responded to ceftizoxime and none to amoxycyllin. Both treatments were well tolerated, the only two adverse effects occurring in the ceftizoxime group. PMID- 2206815 TI - Pharmacokinetic study of controlled-release choline theophyllinate in elderly patients. AB - Controlled-released choline theophyllinate tablets (Sabidal SR 270, Zyma) were administered to 17 elderly patients aged between 68 and 86 years (mean 76 +/- 7 years) until steady state was obtained. The dosage form was one tablet every 12 hours for four days. Plasma theophylline concentrations were measured by high performance liquid chromatography after the first dose and during the fourth day for a 12-hour period. The tablets showed evidence of controlled-release properties: the maximum plasma concentration (10.8 +/- 2.5 mg/l) was obtained after 3.4 +/- 1.6 hours. The mean trough level was 6.6 +/- 1.5 mg/l and the difference between the peak and trough levels was 4.1 +/- 1.2 mg/l. The mean steady-state plasma theophylline concentration was 8.5 +/- 2.2 mg/l. The mean elimination half-life was 14 +/- 7 hours. The mean volume of distribution was 0.8 +/- 0.4 l/kg. The mean total body clearance was 0.05 +/- 1/h/kg. All values, the half-life excepted, were found to be within the ranges for the patients reported in the literature. The values show the usual interindividual variation. PMID- 2206816 TI - Effect of using alcoholic and non-alcoholic skin cleansing swabs when sampling blood for alcohol estimation using gas chromatography. AB - A study was carried out using 20 volunteers in whom venepuncture through the skin soaked in either ethyl or isopropyl alcohol was performed. A non-alcoholic cetrimide/chlorhexidine swab was used as a control. All subjects were initially alcohol free. Ethyl alcohol was detected in only one blood sample and the level was found to be only 0.4 mg% (roughly the limit of detection of the assay). A slightly higher level of isopropyl alcohol (3 mg%) was found in one of the blood samples. Alcohol estimation was carried out by head-space gas chromatography using a pair of instruments each fitted with a column exhibiting different retention characteristics. The system was similar to that used by other UK Forensic Science Laboratories where accurate, definitive results are a necessity. It was concluded that under very testing conditions only minute ethanol interference is produced by using alcohol-based skin cleansing swabs. This minimal interference is unlikely to affect clinical sample results, and even in a forensic situation the inadvertent use of alcohol-based swabs is unlikely to lead to a miscarriage of justice. PMID- 2206818 TI - Three 'silent' mastoid abscesses. AB - Acute mastoiditis with abscess formation is uncommon, its incidence being modified by modern antibiotic usage for acute suppurative otitis media (ASOM). It tends to occur in young children who have no previous history of ear disease. The diagnosis is a clinical one, and treatment requires hospital admission and some form of surgical drainage procedure, in order to prevent intracranial complications, eg, meningitis and intracerebral abscess. PMID- 2206817 TI - The body-worn alarm in the treatment of childhood enuresis. AB - Two studies examined the effectiveness of the body-worn alarm in out-patient treatment of childhood nocturnal enuresis. The first involved 40 children, previously untreated by conditioning methods, treated with either the body-worn alarm or the traditional pad and bell alarm. The second study compared the body worn alarm with modified dry-bed training with 48 children previously resistant to treatment. Results of both studies indicated the body-worn alarm was as effective as other methods in terms of the proportion of children successfully treated and was superior with respect to rapidity of response and consumer appeal. Such findings indicate that the body-worn alarm could become the treatment of choice for nocturnal enuresis. PMID- 2206819 TI - Subacute non-bolus intestinal obstruction caused by Ascaris lumbricoides. PMID- 2206820 TI - Acute anal pain and ingested foreign body impaction. PMID- 2206822 TI - Combined endoscopic cytology and biopsies in the diagnosis of duodenal malignancy. AB - The value of combined cytohistochemical examination in the diagnosis of malignant duodenal lesions was assessed in 78 patients with suspicious duodenal lesions seen at endoscopy. Cytological smears were taken using the direct-vision brushing technique and all were processed by the same experienced cytologist. Duodenal malignancy was confirmed histologically in four patients. Endoscopic biopsy was positive for malignancy in three of the patients and cytology was suspicious of malignant change in two patients and positive for malignant change in one patient. Cytology alone confirmed the diagnosis of malignancy in one patient. The cumulative diagnostic yield using both biopsy and cytology was 100%. PMID- 2206821 TI - Lymphocyte transformation in elderly non-insulin-dependent diabetics before and after improved glycaemic control. AB - Mitogen-induced lymphocyte transformation was examined in 23 elderly patients with poorly controlled Type II diabetes before and after achieving improved glycaemic control with sulphonylureas and compared with 11 healthy controls of similar age. No difference between groups was seen after incubation of lymphocytes with phytohaemagglutinin (PHA). Lymphocyte transformation after 10 micrograms/ml concanavalin A (con A) was significantly greater in diabetic patients after improved control and when compared to healthy controls (p less than 0.025). The response to 5 micrograms/ml and 10 micrograms/ml pokeweed mitogen (PWM) was greatest in diabetic patients after effective metabolic control. PMID- 2206823 TI - Disseminated intravascular coagulation and bacterial infections in the elderly. AB - Anticoagulant screening tests (prothrombin time, thrombin time, kaolin-cephalin time and serum fibrinogen levels), platelet count and estimation of fibrinogen degradation products were carried out on 34 elderly patients with proven bacterial infections, 42 elderly patients with suspected bacterial infections and in 20 controls, to investigate the existence of a sub-clinical form of disseminated intravascular coagulation. The prothrombin time was significantly prolonged in bacterial infections of the elderly and subclinical intravascular coagulation was not found to be a feature. The screening tests did not show any correlation with the outcome of the disease or the presence of septicaemia. PMID- 2206824 TI - Breakthrough seizures with generic carbamazepine: a consequence of poorer bioavailability? AB - The bioavailability of carbamazepine from two products (Ethical Generics and Ciba Geigy) and their efficacy with regard to seizure control and incidence of side effects were compared in 23 children with tonic-clonic or complex partial seizures. Mean plasma concentrations of carbamazepine, carbamazepine 10, 11 epoxide and 10,11-dihydro-10, 11-trans-dihydroxy-carbamazepine at comparable sampling times were not significantly different during treatment with the two drug preparations. The incidence of seizures and occurrence of abnormal EEGs were not significantly different during treatment with the two carbamazepine preparations, and, in addition, the overall incidence of side-effects was not significantly different during the two treatment periods. However, neurological side-effects were significantly less during treatment with the Ciba-Geigy product. On the basis of these observations we are confident that the efficacy of these two carbamazepine preparations in children at steady-state is the same. PMID- 2206825 TI - Nephrology and astrology--is there a link? AB - Astrologers presume a link between the susceptibility of particular organs to disease and signs of the Zodiac. A simple test of the positive connection between renal disease and the sign of Libra was undertaken by studying the birth dates of consecutive nephrology in-patient admissions. No significant link was found on analysis, thus disproving the traditional astrologers' claims. PMID- 2206826 TI - Comparison of the efficacy and long-term tolerability of a combination of atenolol and nifedipine with atenolol alone in the treatment of hypertension. AB - This randomised, double-blind crossover study in 30 hypertensive patients has demonstrated that the fixed combination of atenolol (50 mg) and nifedipine retard (20 mg) once daily lowered blood pressure to a significantly greater extent than atenolol (50 mg once daily) alone. In a follow-up six-month open tolerance study there was no evidence of tachyphylaxis, and treatment with the fixed combination was well tolerated. In selected hypertensive patients use of this fixed formulation may result in improved blood pressure control and benefit patient compliance. PMID- 2206827 TI - Mitral valve prolapse in a patient with epidermolysis bullosa. AB - Mitral valve prolapse has been associated with several connective tissue and developmental disorders, including Ehlers-Danlos syndrome, Marfan's disease; pseudo-xanthoma elasticum, myotonic dystrophy, cardiomyopathy, Ebstein's anomaly of the tricuspid valve and atrial septal defect of the ostium secundum variety. Presented here is a case of mitral valve prolapse in a patient with epidermolysis bullosa. The author is unaware of any previously reported cases of this association. PMID- 2206829 TI - Group G streptococcal septic arthritis. AB - The Lancefield group G streptococcus is known to be a cause of serious infective illness. However, few cases of septic arthritis are recorded. Only one report of this infection, following total joint replacement, has appeared in the orthopaedic literature. Here we describe a further case of infection in a previously normal joint that presented with unusual clinical findings and radiographic changes. We stress the importance of accurate bacteriological investigation and aggressive treatment. PMID- 2206828 TI - Zoster sine herpete. AB - A 61-year-old man presented with acute facial pain and subsequently developed the rash of herpes zoster in a distal dermatome. Treatment with acyclovir was commenced before development of the rash. The atypical presentation and the benefits of early diagnosis and treatment are discussed. PMID- 2206830 TI - Pulmonary agenesis associated with fourteen other congenital abnormalities. AB - Pulmonary agenesis is a rare congenital defect associated with certain previously described anomalies. This is the first case described associated with exomphalos. In addition there were 13 other congenital defects, three of which have not previously been recorded with either condition. PMID- 2206831 TI - Fournier's gangrene and crepitus in the perineum. AB - The diagnosis of Fournier's gangrene is usually simple. However, as this case illustrates, there are occasions when the clinician may be misled. PMID- 2206832 TI - The role of free radicals in ischaemic myocardium. PMID- 2206833 TI - Clips or sutures for herniorrhaphy wounds? AB - This study compares the pain experienced by fifty patients following bilateral herniorrhaphy using two different methods of wound closure. No significant difference was found between the use of Michel clips and interrupted monofilament nylon sutures. Clips were preferred by a significant majority of patients, probably because they cause less pain on removal. The use of Michel clips should not be limited by the belief that they cause more pain than conventional sutures. PMID- 2206834 TI - Proteinuria--the doctor needs to be told. PMID- 2206835 TI - Repair of infected defects of the chest wall by transposition of greater omentum. AB - Myocutaneous flaps have a firm role in the reconstruction of soft tissue defects. Furthermore the supply of extremely infected defects of the chest wall with involvement of the ribs is problematic, especially in irradiated regions. The use of the omental transposition flap is an alternative to the latissimus dorsi myocutaneous flap in treatment of such a deficiency associated with necrosis of the ribs and uncovered pleura. The authors have used this method successfully on eight patients. The scope of this technique is not confined to the chest wall. It can also be extended to defects of the region of the axilla and other parts of the body. For checking the extension and constitution of the greater omentum pre operatively a laparoscopy under local anaesthesia is always carried out. All patients seen by the authors experienced primary healing of the omentum and chest wall. After surgical resection of primary or metastatic chest wall malignancies, irradiation is essential or useful in many cases. Risks of this therapy include damage to underlying parenchyma and overlying skin. The overall incidence of chest wall ulceration from radiation therapy for breast and chest wall lesions is about 5%. In most cases, however, the defects are often the product of both radiation and surgical trauma. These generally deep, foul-smelling and infected wounds are an extreme burden for the patient and a challenge for the surgeon. Conservative treatment never results in wound closure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206836 TI - Comparison of the efficacy and tolerability of diclofenac gel (Voltarol Emulgel) and felbinac gel (Traxam) in the treatment of soft tissue injuries. AB - In an observer-blind, randomised study, the efficacy and tolerability of two topical NSAID preparations were assessed in 384 patients with acute soft tissue injuries. The patients were allocated to receive treatment with either diclofenac gel (Voltarol Emulgel) 4 g tds or felbinac gel (Traxam) 4 g tds for three or seven days, depending on the rate of recovery. In every parameter studied (pain at rest, pain on movement, pain on local pressure, swelling, range of movement, bruising, degree of recovery, requirement for rescue analgesics, daily pain levels), diclofenac was found to be more effective at day 3 and day 7, with the single exception of bruising at day 7. Treatment differences were statistically significant in favour of diclofenac for pain at rest (p = 0.03) and bruising on day 3 (p = 0.03), and pain on pressure at day 7 (p = 0.009). The difference in favour of diclofenac in reduction of daily pain level (as recorded on diary cards) did not quite reach significance (p = 0.06). Both preparations were well tolerated, with no significant treatment-related side-effects reported. PMID- 2206837 TI - Which respiratory anti-infective agent? PMID- 2206838 TI - Colonic lipoma presenting with recurrent rectal bleeding. AB - A case of colonic lipoma in a patient who presented with rectal bleeding is presented. The final diagnosis was established at histology. Rarity of the symptomatic colonic lipomas is highlighted. PMID- 2206840 TI - Pelvic haemangio-pericytoma. PMID- 2206839 TI - Angiodysplasia associated with hypertrophic obstructive cardiomyopathy (HOCM). PMID- 2206841 TI - Abolition of electrocardiographic pattern of left ventricular aneurysm by posterior myocardial infarction. AB - We report a patient who presented with prominent gastrointestinal symptoms in whom a confident clinical diagnosis of acute posterior myocardial infarction was facilitated because the fresh electrocardiographic changes of true posterior myocardial infarction abolished the old pattern of left ventricular aneurysm. This interesting electrocardiographic phenomenon has not, to our knowledge, been previously reported. PMID- 2206842 TI - Haemophilus aphrophilus endocarditis. AB - We report a case of Haemophilus aphrophilus endocarditis involving mitral and tricupsid valves in a boy with congenital heart disease. He had received dental treatment without antibiotic cover. Prolonged high-dose ampicillin with gentamicin was necessary for cure. Short courses of ampicillin alone may not successfully treat H. aphrophilus. PMID- 2206843 TI - Intestinal obstruction secondary to uterine perforation: an unusual cause of vaginal bleeding. AB - A patient with intestinal obstruction is described in whom small bowel was incarcerated within the uterine lumen. This is thought to have arisen as a result of undiagnosed uterine perforation during a previous dilatation and curettage. PMID- 2206844 TI - Hydatid disease and cholestasis. PMID- 2206845 TI - Wiskott-Aldrich syndrome: fatal consequences of splenectomy in an unrecognised attenuated variant. AB - Monozygotic twin males with an attenuated variant of the Wiskott-Aldrich syndrome (WAS) are described. Diagnostic features included moderate thrombocytopenia with small platelet size and abnormal platelet aggregation responses, chronic eczema, depressed serum IgM and low isoagglutinin titre. Splenectomy was performed on one twin at age seven years who survived a complicating pneumococcal septicaemia ten days after the procedure, but who succumbed to fulminating infection three years later. The importance of recognising the attenuated variants of WAS is discussed. PMID- 2206846 TI - Spatially-localized NMR spectroscopy employing an inhomogeneous surface-spoiling magnetic field gradient. 1. Phase coherence spoiling theory and gradient coil design. AB - The use of a current-generated, inhomogeneous, surface-spoiling magnetic field gradient for enhancing magnetic resonance spatial localization, by rapidly inducing spin phase incoherence in surface lying regions of a sample is examined theoretically. A geometrically simple surface-spoiling magnetic field gradient coil design is presented and its gradient field characterized via computer simulations. Mathematical expressions describing the time dependence of net sample spin phase coherence under influence of the spoiling gradient are developed for application with homogeneous (B1) volume coils. The dependence of spoiling efficiency on the magnetogyric ratio of the nuclide under investigation and on the current driving the gradient field is described. Spoiling periods of ca 1-2 ms with driving currents of ca 0.5-1.0 A are predicted to be adequate for surface-spoiling experiments with rat, e.g., for noninvasive monitoring of liver. A companion article (W. Chen and J.J.H. Ackerman, NMR Biomed., 3, 158-165 (1990)) describes implementation of the surface-spoiling technique with multicompartment models (phantoms) and with rat in vivo. PMID- 2206847 TI - Spatially-localized NMR spectroscopy employing an inhomogeneous surface-spoiling magnetic field gradient. 2. Surface coil experiments with multicompartment phantom and rat in vivo. AB - The use of inhomogeneous surface-spoiling magnetic field gradients for elimination of signal from surface lying regions of a sample was theoretically examined in the companion article (W. Chen and J.J.H. Ackerman, NMR Biomed. 3, 147-157 (1990)). Using the spoiling gradient coil design described therein, this article presents experimental verification of the feasibility of such an approach to enhanced spatial localization. Single coil mode 31P NMR surface coil interrogation of both a two compartment phantom and rat in vivo are shown to provide excellent suppression of surface lying regions with minimal degradation of signal from the deep lying region of interest. Both pulse-and-collect and spin echo sequences were highly efficient in concert with spoiling gradient periods of 0.5-2 ms and driving currents of 0.5-2 A. The use of a current-generated surface spoiling gradient offers a robust means to remove surface tissue signal contributions and can be implemented with a wide range of localizing pulse sequences and imaging protocols. PMID- 2206848 TI - Pattern recognition analysis of high resolution 1H NMR spectra of urine. A nonlinear mapping approach to the classification of toxicological data. AB - A computer-based pattern recognition (PR) approach has been applied to the interpretation of 1H NMR generated urinalysis data in a variety of experimental toxicity states in the rat. 1H NMR signal intensities for each endogenous metabolite in urine were regarded as coordinates in multi-dimensional space and analysed using computer pattern recognition methods through which the dimensionality was reduced for display and categorization purposes. Initially 17 metabolic dimensions were used which were defined by the scored relative concentrations of a variety of urinary metabolites detected in 1H NMR spectra. By employing the unsupervised learning methods of 2- and 3-dimensional nonlinear mapping (NLM) different types of toxin (hepatotoxins, cortical and papillary nephrotoxins) could be classified according to NMR-detectable biochemical effects in the urine. The robustness of the classification methods, and the influence of the addition of new scored biochemical data reflecting dose response situations, nutritional effects on toxicity, sex differences in biochemical response to toxins and addition of a new toxin class (testicular toxin) to the pattern recognition analysis were also evaluated. We find that the initial training set maps are fundamentally stable to the addition of all data types and that the PR methods correctly 'predicted' the toxicological effects of the test compounds. These results confirm the power and wide applicability of linked PR and 1H NMR urinalysis as an approach to the generation and classification of acute toxicological data. PMID- 2206849 TI - Renal distribution and metabolism of [2H9]choline. A 2H NMR and MRI study. AB - Trimethylamines are required as substrates in the biosynthesis of a number of important molecules in the cell. Herein, we describe the use of choline, deuterated in its 9 methyl positions, as an NMR label for following the distribution and metabolism of methyl groups after intravenous choline infusion. Deuterium (2H) NMR spectroscopy of the rabbit kidney in vivo revealed a linear uptake of infused choline that was directly proportional to the rate of infusion. The sensitivity limit for the spectroscopic studies in vivo was in the order of 100 microM for a 2 min data collection. After the infusion, 2H NMR imaging of the kidney in vivo demonstrated high trimethylamine concentrations in both the cortex and inner medulla but not in the outer medulla. The inner medullary fraction, however, was more labile to diuresis induced by furosemide. Companion high resolution 2H NMR studies of extracts revealed a cortex betaine/choline concentration ratio of 0.69 +/- 0.05 (mean +/- SEM, n = 3) before furosemide administration. Following furosemide infusion, the cortex betaine/choline concentration ratio was 3 +/- 1 (n = 6). Thus, 2H renal images following furosemide treatment can be interpreted as metabolic maps of betaine distribution. In addition, extraction studies revealed high concentrations of labelled choline and betaine in the liver. These data demonstrate that 2H labelled choline is an effective marker of choline methyl metabolism in vivo and should provide a unique tool for the investigation of this important substrate. PMID- 2206851 TI - 31P chemical shift imaging of the regionally ischemic perfused heart. AB - The application of one-dimensional 31P chemical shift imaging to the study of the isolated perfused rat heart is described. Its applicability for the examination of regional ischemia in the isolated perfused rat heart is demonstrated. The data sets show clearly the localization to the ischemic and nonischemic regions of the heart. Such studies will permit the correlation of cardiac metabolism and function in a controlled manner that is not possible in the application of these techniques to the intact animal. In particular, the time resolution of the experiments will enable spatially localized metabolic studies to be performed during the onset of ischemia and during reperfusion. PMID- 2206850 TI - The combined measurement of blood flow and metabolism in RIF-1 tumours in vivo. A study using H2 flow and 31P NMR spectroscopy. AB - Blood flow and phosphorus metabolites have been measured simultaneously in the murine RIF-1 tumour in vivo. Blood flow was measured using the H2 washout technique and 31P NMR spectroscopy was used to measure high energy phosphates, inorganic phosphate and intracellular pH within the tumour. Following NMR and flow measurements, hydralazine was administered and the measurements repeated. There was always a decrease in blood flow, and a fall in nucleoside triphosphate detected by NMR, after administration of hydralazine. At blood flows in excess of 15 mL 100 g-1 min-1, the nucleoside triphosphate/inorganic phosphate ratio was 1.0 or greater, whereas at flows in the range of 5-12 mL 100 g-1 min-1 the ratio fell to below 0.5, and at flows below 5 mL 100 g-1 min-1 there was no detectable resonance from nucleoside triphosphate. PMID- 2206852 TI - Chronic idiopathic thrombocytopenic purpura: the pediatrician's dilemma. PMID- 2206853 TI - Carboplatin versus cisplatin. PMID- 2206854 TI - A pilot study of high-dose carboplatin and pulsed etoposide in the treatment of childhood solid tumors. AB - Carboplatin was administered at 1,000 mg/m2/course in combination with etoposide at 300 mg/m2/course to 23 patients aged 5 months to 16 years. Five patients were affected by neuroblastoma, four by CNS tumors, three by Ewing's sarcoma, two by rhabdomyosarcoma, two by malignant teratoma, two by Wilms' tumor, two by head and neck carcinoma, one by hepatoblastoma, one by synovial sarcoma, and one by Langerhans-cell histiocytosis. Eleven patients were pretreated, seven of them with high-dose cisplatin. The overall response rate was 7/11 (64%) for pretreated and 10/12 (83%) for previously untreated patients. Myelosuppression was the main side effect, with anemia and thrombocytopenia more pronounced than leukopenia. Gastrointestinal toxicity and ototoxicity were very mild; nephrotoxicity and neurotoxicity other than hearing loss were not observed. In children with malignant tumors, the therapeutic activity of carboplatin at high doses, even in combination chemotherapy, deserves further studies. PMID- 2206855 TI - Acute onset deafness in a 4-year-old girl after a single infusion of cis platinum. AB - Dose-dependent reduction of auditory function mainly in the high frequency range has been described as a common adverse side effect of cis-platinum. Here we report on a 4-year-old girl with osteosarcoma of the right distal femur who developed acute bilateral deafness 3 days after a single infusion of high-dose cis-platinum (150 mg/m2) during preoperative chemotherapy. Sudden disabling ototoxicity should be considered when administering high-dose cis-platinum to young children. PMID- 2206856 TI - The role of computerized tomographic scanning in the management of rhabdomyosarcoma in nonorbital head and neck sites. AB - Computerized tomographic (CT) scans and radiographs of 19 children with nonorbital rhabdomyosarcoma of the head and neck region presenting between 1975 and 1987 were reviewed retrospectively. The scans were assessed for the extent of soft tissue disease and for adverse prognostic features such as the presence of intracranial and parameningeal involvement and for bony destruction. Where applicable, the CT scans were compared with plain radiographs. Follow-up scans after treatment were also reviewed and, where available, histology was correlated with any residual masses. CT was valuable in the initial assessment of the extent of the primary tumor and, therefore, in treatment planning. It was useful in identifying poor prognostic features such as bony destruction and intracranial extension but was not found to be helpful in elucidating the nature of residual or recurrent masses. PMID- 2206857 TI - Four pairs of siblings with acute leukemia during 1966-1985 in the Nordic countries: indication of an elevated familial risk? AB - Four pairs of siblings with acute leukemia in the Nordic countries during 1966 1985 are reported. The national data indicate that the risk of leukemia is 5.9 times greater in siblings of children with leukemia. PMID- 2206858 TI - Homozygous protein C deficiency in two siblings. AB - Homozygous protein C (PC) deficiency is reported in two siblings (girl and boy) who received their proper diagnoses at the ages of 7 4/12 and 1 3/12 years respectively. The girl had perinatal asphyxia without bleeding. At 1 year of age she developed purpura fulminans. Treatment with heparin and plasma was successful. At 7 4/12 years she developed tender, bluish nonnecrotic skin changes after an orthopedic operation. The PC level was 0.08 U/ml. The boy had had a large intraventricular hemorrhage neonatally and developed severe brain damage. At 1 3/12 years he manifested the same skin changes as his sister and was treated similarly. The PC level was 0.05 U/ml. Both children now receive warfarin continuously and are essentially free of symptoms. The cases represent homozygous phenotypes in a family with a recessive trait of PC deficiency without thrombotic disease. The cases also show that severe PC deficiency may be compatible with life beyond infancy without any specific therapy. PMID- 2206859 TI - Intracranial germinoma: report of seven cases. AB - Seven children with histologically verified intracranial germinomas, treated between 1983-1987, are reviewed. The four boys were 12, 14, 15, and 16 years old; two girls were 9, and one girl was 10 years old. Four tumors were suprasellar, and three were in the pineal region. Parinaud's sign was the first symptom in the pineal tumors and diabetes insipidus in the suprasellar ones. The latter four patients also had pituitary deficiencies. The tumors were totally removed in three patients, partially in three, and one patient had biopsy only. Two patients had disseminated tumor. All patients received radiation: four to the tumor bed, one to the whole brain, and two to the whole central nervous axis (CNA). The doses to the tumor were 30 Gy in three, 40 Gy in two (one whole brain), and 45 Gy in two. The dose to the CNA was 24 Gy. Five patients had chemotherapy as well: cyclophosphamid (cytoxan) 80 mg/kg in two doses, three times in 3-week intervals. All patients are alive and well. Total disappearance of tumor followed chemotherapy before radiation in three patients. Lower doses of radiation (30 Gy, 40 Gy) and irradiation of the tumor bed only were sufficient for tumor control in localized germinoma. PMID- 2206860 TI - Acute respiratory failure after intrathecal methotrexate administration. AB - This is a report of a case of acute respiratory failure following the administration of intrathecal methotrexate (MTX) for prophylaxis of central nervous system leukemia (CNS) in a 3-year-old girl with acute lymphoblastic leukemia. This could be attributed to acute metabolic or direct toxic effects of methotrexate to the central nervous system tissue. Although the specific agent responsible for this complication following intrathecal injection of MTX is unclear, it is worthwhile to describe this event. PMID- 2206861 TI - Danazol therapy in immune thrombocytopenic purpura. AB - Nine children with chronic refractory immune thrombocytopenic purpura and moderate to severe episodes of bleeding were treated with Danazol in an attempt to increase their platelet counts and improve clinical hemostasis. Only one patient experienced an excellent response while a good response was obtained in another. Cessation of bleeding episodes was observed in two other children with only marginal increases in platelet counts. Four of the nine patients failed to show any clinical or hematological improvement. The drug was well tolerated but its efficacy in childhood ITP needs further evaluation. PMID- 2206862 TI - Failure to thrive leading to early detection of retinoblastoma. PMID- 2206863 TI - Pulmonary infection mimicking metastases in Ewing's sarcoma. PMID- 2206864 TI - School-related behavior in children with cancer. PMID- 2206865 TI - Imipenem-antibiotic monotherapy in juvenile cancer patients with neutropenia. AB - From 1984 to 1987 two consecutive groups of juvenile cancer patients (n = 45) with fever and neutropenia corresponding in all criteria were examined. In half of the total of 90 febrile episodes and septicemias, a conventional antibiotic combination therapy (Pseudomonas-active penicillin/cephalosporin of the third generation/aminoglycoside) was instituted. In the remaining half imipenem was used as an antibiotic monoagent. In 66% and 60% of the febrile episodes treated with antibiotic combination therapy and with imipenem, respectively, septicemia was confirmed by positive blood cultures. Nineteen febrile episodes occurred in the myeloaplastic phase after bone marrow transplantation. In a comparative study of imipenem as monotherapy versus an antibiotic combination therapy the results obtained with imipenem were superior in many regards. No resistance developed necessitating change of antibiotic therapy. Coagulase-negative Staphylococci, primarily responsible for catheter-associated septicemia, were susceptible. Duration of fever and thus duration of treatment were shorter. The incidence of side effects and costs were lower. Therefore, imipenem as an antibiotic monotherapy in febrile cancer patients with neutropenia appears to be more efficacious than the conventional combination therapy, even during myeloaplasia following bone marrow transplantation. The results and rationale of this retrospective analysis are discussed. PMID- 2206866 TI - Anthropometric measurements at diagnosis of childhood cancer. AB - Height, weight, upper-arm circumference, sitting height, armspan, and head circumference were measured in 96 patients at diagnosis of a childhood malignancy. Height of both parents could be measured in 60 cases. Some individuals with acute lymphoblastic leukemia were very tall and some patients with a brain tumor were very small. In contrast, the mean values for height, sitting height, and midparent height were normal in all four groups of patients (with leukemia, solid tumor, brain tumors, and remaining malignancies). Armspan, however, was significantly longer in leukemia and solid tumor patients in comparison with healthy peers. These finding are not considered enough evidence for the existence of an association between tallness and childhood malignancy. Weight (for height) was significantly lower in solid tumor patients than in leukemia patients. PMID- 2206867 TI - Nasopharyngeal rhabdomyosarcoma presenting as a breast mass. AB - We describe a 13-year-old girl with a primary nasopharyngeal rhabdomyosarcoma presenting with an isolated breast metastasis and no other evidence of distant metastatic spread. Only seven cases have been previously reported, and in all these cases the primary tumor was located either on an extremity or the buttock, and in six the disease was widely disseminated at diagnosis. PMID- 2206868 TI - Interleukin 2 immunotherapy in children with neuroblastoma after high-dose chemotherapy and autologous bone marrow transplantation. AB - Four children with persistent neuroblastoma after marrow ablative chemoradiotherapy and autologous bone marrow transplantation received continuous infusion of recombinant interleukin 2, 75 to 120 days after the graft. Recombinant interleukin 2 therapy did not induce any major or nonreversible toxicity, hematological toxicity in particular. One patient entered complete remission for 9 months and a second patient had a long-lasting normalization of urinary catecholamine metabolites with more than 50% regression of bone marrow metastases (8 months). In three children, recombinant interleukin 2 and a second patient entered complete remission for 9 months therapy was followed by major increase and activation of circulating natural killer cells which amounted to 80% of the circulating mononuclear cells. PMID- 2206869 TI - Treatment of refractory aplastic anemia with plasmapheresis: report of a case in childhood with review of the literature. AB - Treatment of aplastic anemia may raise considerable problems in some patients. This report concerns a boy whose illness started at 11 years of age. At first admission laboratory data were: hemoglobin 7.5 g/l, and counts of leucocytes, neutrophils and platelets were 2.3, 0.6, and 8 x 10(9)/l, respectively. His bone marrow was hypoplastic with sparse erythropoiesis. The patient did not respond to traditional medical treatment. Serum contained a high concentration of erythropoietin but no antibodies against erythropoietin. The patient's serum did neither alone, nor supported with recombinant erythropoietin, stimulate erythropoiesis in a bioassay, suggesting that some factor(s) inhibiting erythropoietic activity was present. Based on this hypothesis, plasma exchange was performed. After 26 weeks of plasmapheresis the hematological parameters were normalized. We conclude that plasmapheresis might be an alternative in treatment of resistant aplastic anemia. Further diagnostic tools to identify patients who might benefit from such a treatment are required. PMID- 2206870 TI - Ruptured spleen as a cause of death in an infant with Langerhans cell histiocytosis (histiocytosis X). PMID- 2206871 TI - Nutrition, infection, and morbidity in leukemia. PMID- 2206872 TI - Evaluation of long-term aggressive dietary management of chronic renal failure in children. AB - Ten children with chronic renal failure (CRF) were managed for 3 years using a strict low-protein and low-phosphorus diet supplemented by a mixture of the keto and amino forms of the essential amino acids and histidine (phase II). All of these children were previously managed for at least 2 years with a less rigorous diet of limited protein intake with no specific reduction of phosphorus (phase I). Energy, vitamin D, bicarbonate, phosphate binders and vitamin and mineral mixtures were added as required during both dietary phases. Data on dietary intake showed a significant fall in protein and phosphorus intake and a rise in calcium intake during phase II compared with phase I. Plasma calcium increased and phosphate fell, with an associated fall in intact parathyroid hormone levels. There was a marked improvement in urea creatinine ratios, which suggested an improved anabolic state. Cholesterol and triglyceride levels were improved. Height and weight velocity were increased, becoming significant after 3 years of phase II. Renal function deteriorated at a slower rate than predicted. The diet was well tolerated by the children, with fitness and school performance showing improvement. We conclude that long-term strict dietary management of children with CRF is feasible. Our data suggest an overall improvement in general health and an apparent reduction in the rate of deterioration of renal function. PMID- 2206873 TI - A longitudinal study of the cognitive function of children with renal failure. AB - Fifty-six children with chronic renal failure who either received a kidney transplant, were hemodialyzed or peritoneally dialyzed, or who were being medically managed were given a series of neuropsychological tests every 6 months for a total of four testing sessions. Each child was matched by age, sex, and race to healthy children who received the same sequence of tests. The performance of each treatment group was compared with their controls longitudinally, using a repeated measure analysis of variance. In general, renal subjects performed at lower levels than their controls on tasks of verbal ability, visual perception, memory and visual motor skills. Visual motor performance was the most clinically affected. When compared with controls, the renal subjects did not improve as much or actually deteriorated on some measures of memory and learning skills. PMID- 2206874 TI - Association between renal function and cognition in childhood chronic renal failure. AB - Forty-five children with renal failure who were either being medically managed, receiving dialysis (hemodialysis or continuous ambulatory peritoneal dialysis) therapy or who had received successful kidney transplants were longitudinally examined on multiple neuropsychological measures. A variety of medical parameters was also obtained at each time of testing. The neuropsychological variables were correlated with the medical variables using the repeated measures regression analysis method. There were associations between levels of renal function, short term memory and list learning. Other neuropsychological variables did not in general correlate with the medical parameters consistently for all ages at the time of initial testing. Verbal performance decreased with increasing duration of renal failure in 6- to 11-year-olds and immediate recall decreased with increasing percentile rank of systolic blood pressure in 16- to 18-year-olds. PMID- 2206876 TI - What is the value of distinguishing pathophysiological subgroups and what is the appropriate duration of specific therapy in children with significant hypercalciuria? PMID- 2206875 TI - Recurrence of focal segmental glomerulosclerosis in transplanted kidneys: analysis of incidence and risk factors in 59 allografts. AB - Fifty-nine allografts were placed in 43 patients with renal failure from focal segmental glomerulosclerosis (FSGS): 27 allografts were put into 16 children aged less than 15 years, and 32 allografts into 27 adolescents and adults. Recurrence of FSGS was noted histologically in 13 allografts, 10 in 8 children and 3 in adults. None of the 9 children and 24 adults who never developed an allograft nephrotic syndrome showed FSGS in their allograft biopsies. The age of onset was a strong risk factor for recurrence: recurrent FSGS developed in 8 of 16 children (50%) but only in 11% of adolescents and adults (3 of 27 patients). Although the time from apparent onset to renal replacement treatment was shorter in those with recurrence than those without in the children, there was no difference in the time spent on dialysis prior to transplantation. Mesangial prominence was observed in the original biopsy in 12 of 13 patients with recurrence, and recurrence rate was similar in living and cadaver donor allografts; class I MHC matching was similar in those with and without recurrence. Three allografts treated with cyclosporin A as well as 9 with azathioprine showed recurrence. Of 9 second or subsequent allografts placed in those with recurrence in the first allograft, only 3 showed further recurrence. In 3 re-grafted after 13, 11 and 5 years, normal function was seen. PMID- 2206877 TI - Adrenal calcification and congenital nephrotic syndrome in three American Indians. AB - Two Pima and one Papago Indian infants with congenital nephrosis and adrenal calcifications are described. All developed anasarca early and none had an explanation for the adrenal calcification. PMID- 2206879 TI - Spontaneous remission of nephrotic syndrome in a patient with IgA nephropathy. AB - A patient with spontaneous remission of nephrotic syndrome (NS) associated with IgA nephropathy is described. The patient presented at the age of 8 years with asymptomatic proteinuria, and at the age of 11 years developed classical features of NS. A percutaneous renal biopsy showed mild mesangial prominence without significant hypercellularity, electron-dense deposits within the mesangium, and 3+ mesangial staining with IgA and IgG. NS resolved 6 weeks after onset without any form of therapy; absence of proteinuria persisted 6 months later. This report demonstrates clearly that patients with NS associated with IgA nephropathy may undergo spontaneous resolution of their proteinuria. PMID- 2206878 TI - Intravenous immunoglobulin in minimal change nephrotic syndrome: a crossover trial. AB - To determine whether intravenous immunoglobulin (IVGG) would be an efficacious adjunct in the treatment of childhood minimal change nephrotic syndrome (MCNS), we enrolled ten patients with frequently relapsing or steroid-dependent MCNS in a double-blind crossover clinical trial. At the time of relapse of the nephrotic syndrome, patients were assigned to treatment with a single outpatient infusion of IVGG (800 mg/kg) or intravenous albumin as a control. The relapse was treated concurrently with standard doses of oral prednisone. At the time of the next relapse, patients who had first received IVGG were treated with albumin, and vice versa. There were no significant differences in the length of remission between the IVGG and albumin treatments. The study had a power of 0.72 to detect a true difference of 45 days between the two therapies. We conclude that in the dose of drug used in this trial, administered at the time of relapse in conjunction with prednisone therapy to children with frequently relapsing or steroid-dependent MCNS, IVGG does not lead to a clinically important extension of the period of remission. PMID- 2206880 TI - Glomerular function and microalbuminuria in children with insulin-dependent diabetes. AB - Renal function has been evaluated in 45 diabetic children (age 12.5 +/- 4 years) with a mean diabetes duration of 4.9 +/- 3.5 years. Glomerular filtration rate (GFR; inulin and creatinine clearances), renal plasma flow (RPF; PAH clearance), resting urinary albumin excretion (UAE) were measured and compared with indexes of metabolic control: Hb A1C and blood glucose values (mean, post-prandial and maximal excursion) on the same day. GFR (inulin clearance) and RPF were significantly increased in the diabetic group (171 +/- 31 and 778 +/- 172 ml/min per 1.73 m2) compared with controls (124 +/- 18 and 631 +/- 128 ml/min per 1.73 m2). Both parameters were strongly correlated (r = 0.73; P less than 0.001). Creatinine clearance was not correlated to inulin clearance. Hyperfiltration (inulin clearance above 160 ml/min per 1.73 m2) was noted in 61% of the patients and was independent of diabetes duration. Five diabetic children had a UAE level above 15 micrograms/min. No relationship could be established between UAE and any of the metabolic indexes; GFR was weakly correlated to HbA1C (r = 0.35; P less than 0.05), to mean (r = 0.37; P less than 0.05) and post-prandial blood glucose (r = 0.37; P less than 0.05). In contrast, there was a strong correlation between GFR and the maximal blood excursion (r = 0.62; P less than 0.001). The study shows that renal abnormalities can be detected with a high frequency in diabetic subjects characterized by both an early onset and a short duration of diabetes and suggests the need for a more systematic evaluation of renal parameters in this population. PMID- 2206881 TI - Renal tubular dysfunction in fetal alcohol syndrome. AB - Renal function was evaluated in six patients with fetal alcohol syndrome (FAS) and eight control subjects before and after fluid restriction and acute acid loading. Baseline serum electrolytes, creatinine clearance, fractional sodium excretion, tubular reabsorption of phosphate, urine and blood pH and osmolalities, plasma renin activity, and plasma aldosterone level were normal in all subjects, but fractional potassium excretion (FEK) was lower in FAS patients than in control subjects (P less than 0.001). Despite equivalent plasma osmolalities (295 +/- 3 vs 293 +/- 2 mosmol/kg, P = 0.2), the maximum urinary osmolality after 12 h of water deprivation in patients with FAS was significantly lower compared with controls (560 +/- 107 vs 965 +/- 77 mosmol/kg; P less than 0.001) and increased to only 578 +/- 101 mosmol/kg after vasopressin administration. After ammonium chloride loading, minimum urine pH was significantly higher in patients than in controls (5.7 +/- 0.17 vs 4.81 +/- 0.19; P less than 0.001). Net acid excretion and FEK were also lower in patients than in controls (102 +/- 11 vs 139.6 +/- 11.3 microEq/min per 1.73 m2 and 23.5 +/- 1.3 vs 29 +/- 1.6%, respectively; P less than 0.001). The data indicate a subclinical renal tubular defect in urine concentration and acidification in patients with FAS. PMID- 2206882 TI - A clinicopathological study of 24 children with hemolytic uremic syndrome. A report of the Southwest Pediatric Nephrology Study Group. AB - This study reports the pattern of renal injury in 24 North American children with hemolytic uremic syndrome (HUS), and the extent of extrarenal involvement in 9 of these children examined at autopsy. Fifteen of the 24 children were studied during the first 16 days of hospitalization; their renal specimens demonstrated glomerular thrombotic microangiopathy (TMA) in 8 children, cortical necrosis in 1, and varying degrees of glomerular TMA and cortical necrosis in 6 children. Nine of the children were studied after 16 or more days of hospitalization; these patients had prominent renal arterial lesions. Of 9 children examined at autopsy, extrarenal microthrombi were identified in 8. In 4 children who died during the acute phase of the disease, hemorrhagic colonic necrosis (3 children) and pancreatic islet cell necrosis (2 children) were the principal extrarenal lesions encountered. Rare microthrombi were present in the brains of the 3 children who manifested seizures. PMID- 2206883 TI - The expression of blood group P1 in post-enteropathic haemolytic uraemic syndrome. AB - Blood group P1 expression was scored by direct agglutination in 32 patients who had previously developed post-enteropathic haemolytic uraemic syndrome (HUS). Sixty-six children of similar ages undergoing venepuncture for other renal disorders acted as controls. The expression of P1 in controls was that expected from the normal caucasian population, 23% being negative. By contrast, there was an excess of HUS patients with weak or absent expression of P1 (chi 2 for linear trend 5.45, P less than 0.02), and this was particularly evident in those with a poor outcome. Verotoxin (VT), which is associated with HUS, requires the terminal disaccharide of the P1 antigen to bind to cells, and after internalization disrupts the transcription of ribonucleic acid. Mature erythrocytes do not synthesize protein and may be toxin resistant. We postulate that strong expression of P1 antigen may promote the binding of VT to red cells and thus reduce the dose to vulnerable nucleated endothelial cells. P1 positivity may be protective, and P1 negativity a risk factor in HUS. PMID- 2206885 TI - Haemolytic uraemic syndrome with prolonged anuria and cortical calcification: a case report. AB - An 18-month-old infant presented with haemolytic uraemic syndrome following a prodrome of colitis. Incomplete recovery of renal function occurred after 4 weeks of anuria and was associated with extensive renal cortical calcification. During the recovery phase he had two relapses of colitis, microangiopathic haemolytic anaemia and thrombocytopenia without any deterioration in renal function. PMID- 2206884 TI - De novo hemolytic uremic syndrome following renal transplantation. AB - We report a case of complete recovery of renal function in a patient with de novo hemolytic uremic syndrome (HUS) following renal transplantation. This 3-year-old girl had none of the factors known to contribute to the development of HUS in transplant recipients. This case illustrates the usefulness of renal biopsy in the accurate diagnosis and management of dysfunction in the allograft following renal transplantation. PMID- 2206886 TI - Association of fever, nasal congestion and rise in serum creatinine with azathioprine therapy. AB - The association of fever, nasal congestion and reversible rise in serum creatinine in a patient receiving azathioprine is reported. An identical pattern of symptoms was induced after two rechallenges with azathioprine. The increases in serum creatinine were not associated with renal parenchymal abnormalities. This paper illustrates that in transplanted patients, fever and rises in serum creatinine are not only related to rejection or infection, but may also involve drug hypersensitivity. PMID- 2206887 TI - Renal cysts in pediatric patients. A classification and overview. AB - Renal cysts are relatively common. They may be single, multiple, or innumerable, cortical or medullary. Most renal cysts are spherical, thin-walled, epithelial lined structures that contain fluid with features of a plasma ultrafiltrate. A clinically useful classification must include characteristics such as age of onset, family history and association with extrarenal lesions, as well as morphologic parameters. Renal dysplasia is disturbed renal histogenesis, either syndromic or non-syndromic, which usually gives rise to morphologically characteristic renal cysts. Two important and distinctive familial forms of renal polycystic disease occur. Autosomal dominant polycystic disease characteristically becomes manifest in adulthood but is becoming increasingly diagnosed in young individuals. Autosomal recessive infantile polycystic disease has complex relationships with "congenital hepatic fibrosis". Other cystic renal lesions are less common in young patients, but their occurrence in association with other abnormalities provokes speculation regarding pathogenesis. PMID- 2206889 TI - What is the role of the intrarenal renin-angiotensin system in blood pressure control? PMID- 2206891 TI - Advisability of initiating chronic peritoneal dialysis in the presence of a ventriculoperitoneal shunt. PMID- 2206890 TI - Biopty device for obtaining kidney specimens. PMID- 2206892 TI - Clinical quiz. Pseudoxanthoma elasticum (PXE). PMID- 2206888 TI - Glomerular fibrin deposition and removal. AB - Glomerular fibrin deposits may occur within vessels or in extracapillary crescents. Studies suggest that intravascular thrombosis is promoted by endothelial cell activation/injury, resulting in the release of endothelial-cell derived tissue factor procoagulant, fibrinolytic inhibitors, platelet activating factor, and large multimers of von Willebrand factor. Fibrin in crescents may arise from coagulation of plasma in Bowman's space mediated by the release of tissue factor from infiltrating macrophages. Glomerular fibrin may be removed by fibrinolytic or phagocytic mechanisms or persist and lead to glomerular obsolescence. Suppression or elimination of factors that promote glomerular fibrin deposition and enhancement of mechanisms that remove glomerular fibrin may be important in the recovery from several forms of human kidney disease. PMID- 2206893 TI - What treatment do you advise for a small child with hyperoxaluria presenting with renal calculi? PMID- 2206894 TI - Treatment of steroid-resistant focal segmental glomerulosclerosis with pulse methylprednisolone and alkylating agents. AB - In children, steroid-resistant nephrotic syndrome due to focal segmental glomerulosclerosis (FSGS) is frequently a progressive condition resulting in end stage renal disease. There have been no reports of effective treatment for this condition. For the past several years, the Pediatric Nephrology services at the University of California, San Diego and Stanford University Schools of Medicine have treated these patients with a protocol involving infusions of high doses of methylprednisolone, often in combination with oral alkylating agents. Twenty three children have been treated in this manner with a follow-up of 46 +/- 5 months. Twelve of these children are in complete remission. Six have minimal to moderate proteinuria. Four children remain nephrotic. Each of these children has a normal glomerular filtration rate. One child developed chronic renal failure and subsequently died while on dialysis. These results appear significantly better than previous series of children with FSGS. A controlled, multi-center trial of this protocol has been proposed. PMID- 2206895 TI - What is the cause of sodium retention in acute nephritis? PMID- 2206896 TI - Fanconi syndrome, ichthyosis, dysmorphism, jaundice and diarrhoea--a new syndrome. AB - We describe six infants, from consanguineous marriages, with a new syndrome comprising the Fanconi syndrome, ichthyosis, musculoskeletal abnormalities, jaundice and diarrhoea. In addition two of the infants were found to have abnormal platelet morphology--the grey platelet syndrome. No evidence of a recognised metabolic disorder was found in any of the six infants, nor did they appear to be typical of any previously described syndromes. Their progress was poor: they required high fluid and bicarbonate intakes and all died by the age of 6 months of dehydration, acidosis and sepsis. PMID- 2206897 TI - What treatment would you advise for a 1-year-old child with chronic renal failure who has been on aluminum hydroxide as a phosphate binder for 6 months and then develops epilepsy and is found to have a grossly raised plasma aluminum concentration? PMID- 2206898 TI - Risk factors in internal urinary system malformations. AB - Risk factors were studied in 370 children with internal urinary system (IUS) anomalies, coming from 105,374 consecutive births of known outcome. The incidence of IUS malformations was 3.51 per 1,000 births. Diagnosis was performed prenatally in 54.4% of patients. Two hundred and fifty-two patients had isolated IUS anomalies; 118 (31.8%) of the children had at least one non-urinary malformation. Fifty-five infants (14.8%) had recognized chromosomal and non chromosomal syndromes. The more frequent non-urinary malformations were cardiac, digestive and limb anomalies. For each case a control was studied. The following features were assessed: sex ratio, parity and previous pregnancies, parental age, residency, education, ethnic origin, length, head circumference and weight at birth, genetic and environmental factors. Odds ratio values were calculated for risk factors. Weight, length and head circumference at birth were less than in the controls and the weight of the placenta was lower. Pregnancies with IUS anomalies were more often complicated by oligo-amnios and threatened abortions. Oligo-amnios was more frequent in pregnancies in which babies had multiple malformations and recognized syndromes with IUS anomalies. One child of every three with IUS anomalies had an extra-urinary malformation, which is 12 times the incidence of such malformation in our population. There was an increase in consanguinity in the parents of our patients. The incidence of IUS anomalies in first-degree relatives was 2.9%. First-degree relatives had more non-urinary malformations than controls (7.02 vs 3.2%). Our study demonstrated the high capacity of a general ultrasound screening programme to detect fetal malformations affecting the urinary tract. PMID- 2206899 TI - Mechanism of orthostatic proteinuria. PMID- 2206901 TI - Familial infantile nephrotic syndrome with ocular abnormalities. AB - Two siblings born from consanguineous parents experienced infantile nephrotic syndrome with ocular and neurological abnormalities; the boy also had a micropenis; both patients died before age 1 year. An initial renal biopsy followed by a two-step binephrectomy allowed good histological assessment of disease progression in one patient. The progression of the lesions was characterized by mesangial involvement, then an extensive extracapillary proliferation and tubular dilatations with a high mitotic activity of the epithelium and nuclei of unequal size. The main features involved major ultrastructural changes of the glomerular basement membrane. These two patients may represent a new disease entity or a severe form of diffuse mesangial sclerosis, with autosomal recessive inheritance. PMID- 2206900 TI - Growth in children following kidney transplantation. AB - Growth was assessed in children following 128 separate kidney transplants using a generalized growth curve multivariate analysis. The height standard deviation score was the dependent variable. Time since transplant, prednisone dosage, and creatinine clearance were the independent variables. For the purposes of comparison patients were grouped according to sex, race, age at transplantation, initial allograft function, acute rejection episodes and the use of cyclosporin A. Patient's height standard deviation scores tended to increase negatively after transplantation. However, children who received transplants before their 7th birthday, with initial allograft function greater than 60 ml/min per 1.73 m2, exhibited "catch-up" growth. Height standard deviation scores positively improved in males but not in females, as prednisone dosage was decreased. Height standard deviation scores became more negative as renal function decreased after transplantation. Changes in renal function produced the greatest effect upon height in black children, children less than 7 years, and males. PMID- 2206904 TI - Management of acute renal failure in children. PMID- 2206903 TI - Renal regulation of salt balance: a primer for non-purists. AB - The greater than 40-fold range of voluntary salt intake in humans requires corresponding adjustments in renal excretion to maintain balance. Although many mechanisms have been implicated in the regulation of salt output by the kidney, surprisingly little consideration has been given to their quantitative significance and possible interaction. This survey summarizes the effects of changes in glomerular filtration rate, proximal peritubular physical factors, and plasma concentrations of aldosterone and atrial natriuretic factor (ANF), singly and in combination, on the level of salt excretion. Contrary to expectation, even large increases in filtration or decreases in proximal reabsorption have only minor natriuretic effects, due to constancy of fractional reabsorption in downstream nephron segments. Lack of aldosterone release increases salt excretion as much or more than the upstream mechanisms, whereas ANF-induced inhibition of reabsorption in the medullary collecting duct has the largest effect. It may be concluded, therefore, that the potency of these natriuretic factors increases with distance along the nephron, even though each is operating on a progressively small tubular load. However, none of the mechanisms, in isolation, is sufficient to explain salt balance over the range of voluntary intake. Combination of factors demonstrates synergism rather than simple additivity, resulting in more than enough reserve capacity for salt excretion. PMID- 2206905 TI - Proceedings of the Fourth International Workshop on Developmental Renal Physiology. August 24-26, 1989, Montreal, Canada. PMID- 2206902 TI - Polypeptide growth factors and the kidney: a developmental perspective. AB - A variety of polypeptides with stimulatory or inhibitory effects on cell proliferation have been identified. In addition to stimulating or inhibiting the proliferation of cells and maintaining their viability, polypeptide growth factors play significant roles in embryogenesis and differentiation. The current review focuses on five specific polypeptide growth factor families (epidermal growth factor, insulin-like growth factors, transforming growth factors, platelet derived growth factor, and fibroblast growth factors) and discusses their possible relationship to normal renal physiology, abnormal renal pathophysiology, and renal organogenesis. On the basis of current data, it is clear that polypeptide growth factors are multifunctional agents with important effects on renal function and renal organogenesis. PMID- 2206908 TI - Regulation of renal phosphate reabsorption during development: implications from a new model of growth hormone deficiency. AB - It has been hypothesized that the high rate of renal phosphate (Pi) reabsorption in the immature animal is a consequence of the increased demand for Pi associated with the rapid rate of growth. Although growth hormone (GH) has been proposed to play a role in this process, investigations of the relationship between GH, growth and the renal Pi transport have been hampered by the lack of methods available to specifically alter circulating GH levels. This review summarizes the findings from recent studies using a newly developed peptidic antagonist to GH releasing factor (GRF-AN) as a method of specifically inhibiting GH release. Systemic injection of GRF-AN was effective in suppressing the pulsatile release of GH, and in significantly attenuating the rate of growth, in both immature and adult rats. However, the inhibition of growth was associated with a reduction in net Pi retention only in immature rats, resulting in a doubling in the urinary excretion of Pi. GRF-AN treatment of immature rats lead to a decrease in the maximum tubular capacity to transport Pi-down to the level seen in adult rats. However, GRF-AN treatment did not alter renal Pi reabsorption in adult rats. We conclude that chronic administration of an antagonist to GRF in rats provides a new model of GH deficiency with which to study the interrelationships between growth, GH and other physiological systems. Furthermore, the findings suggest that the pulsatile release of GH, directly or indirectly, contributes to the high rate of renal Pi reabsorption in young, growing animals and may play a critical role in regulating Pi homeostasis during development. PMID- 2206907 TI - Polypeptide growth factors in metanephric growth and segmental nephron differentiation. AB - Although the developing nephron expresses receptors for various polypeptide growth factors, the specific roles of such factors in renal organogenesis are unknown. Therefore, the effects of epidermal growth factor (EGF) (8.2 x 10(-11) M 1.6 x 10(-8) M), multiplication stimulating activity (MSA) (6.6 x 10(-10) M-1.3 x 10(-8) M) and transforming growth factor beta (TGF-beta) (1 x 10(-12) M-1 x 10( 9) M) on organotypic renal growth and segmental nephron differentiation were studied in a serum-free hormone-supplemented, murine metanephric organ culture system. Following culture in control or growth-factor-supplemented medium, explant growth was assessed, and explant growth and differentiation were determined morphometrically in four defined neprhon segments which were identified morphologically or immunohistologically with segment-specific antibodies and/or lectins: glomeruli, proximal tubules, thick ascending limb early distal tubules, and collecting tubules. Results showed that EGF increased overall renal growth and specific differentiation of distal elements, but retarded differentiation of glomeruli and proximal tubules. EGF also induced hyperplastic cystic malformation in proximal tubules. MSA stimulated explant growth and promoted segmental differentiation of all tubular segments. TGF-beta globally retarded in vitro nephrogenesis. Such data demonstrate that polypeptide growth factors have multiple and often disparate effects on overall renal growth in relation to differentiation of discrete nephron segments and provide insight into the factors which may regulate normal and abnormal renal embryogenesis. PMID- 2206906 TI - Kidney epithelial cells release growth factors in response to extracellular signals. AB - The growth of nontransformed monkey kidney epithelial cells in culture appears to be regulated by the interplay of positive and negative autocrine growth factors. Reduction of the potassium or sodium concentration of the medium induces rapid release of novel growth-promoting activities, whereas addition of the mitogen adenosine diphosphate stimulates the appearance of a platelet-derived growth factor-like protein which could function in a paracrine manner. These observations suggest that autocrine and paracrine growth factors could play an important role in physiological and pathological states in the kidney. PMID- 2206909 TI - NMR studies of phosphate metabolism in the isolated perfused kidney of developing rats. AB - During growth, the capacity for renal phosphate (Pi) reabsorption varies as a function of Pi demand. These changes occur in the absence of changes in extracellular concentration of Pi and are also observed in renal cells cultured in defined media. These findings suggest a direct regulatory effect of intracellular Pi on its transport systems. We postulate that a low intracellular Pi concentration [( Pi]i) occurs in the developing kidney as a consequence of differences in Pi metabolism between growing and mature cells and that a low [Pi]i, in turn, leads to adaptive changes in renal Pi transport. In order to assess this hypothesis, we used 31P-nuclear magnetic resonance (NMR) to measure the intracellular concentrations of NMR-visible Pi and phospho-metabolites and the rates of Pi turnover due to adenosine triphosphate (ATP) synthesis, in isolated perfused kidneys of 3- to 4-week-old and 12- to 13-week-old rats. The [Pi]i was lower (1.7 +/- 0.1 vs 2.7 +/- 0.1 mM, P less than 0.05) in kidneys of growing than of adult rats, while the ATP (2.9 +/- 0.3 vs 2.8 +/- 0.5 mM) and adenosine diphosphate (ADP) (-0.2 mM) concentrations were similar at the two ages, consistent with a high phosphorylation potential in the kidneys of the younger animals. Radiofrequency irradiation of the gamma-P of ATP resulted in reduction in the intensity of the Pi resonance of 62 +/- 5% in the newborn and 38 +/- 3% in the adult (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206911 TI - Molecular biology of components of the renin-angiotensin system during development. AB - Evidence for the expression of genes of the renin-angiotensin system (RAS) in the developing kidney is rapidly accumulating. We have recently demonstrated that the fetal kidney expresses the renin gene and that expression of the gene is developmentally regulated. Kidney renin messenger ribonucleic acid (mRNA) levels decrease markedly with maturation, and as maturation unfolds the intrarenal distribution of renin and its mRNA changes from large intrarenal arteries in the fetus to a restricted juxtaglomerular site in the adult animal. These findings demonstrate that renin is synthesized and stored in the aforementioned vascular segments and that expression of the renin gene follows the centrifugal pattern of nephrovascular development. In addition to storing renin, intact kidney microvessels release renin spontaneously and possess a functionally active adenylate cyclase whose stimulation results in a marked increase in renin release. The increase in renin enzymatic activity appears to be due to a recruitment of renin-releasing cells rather than to an increase in the amount of renin secreted per cell. Expression of the angiotensinogen (Ao) gene is also developmentally regulated. Ao mRNA levels are very low in the fetal liver, markedly increasing after parturition, suggesting that some of the complex neurohumoral changes surrounding extrauterine life may regulate the expression of the Ao gene. As in the adult animal, Ao is expressed in fetal kidney, brain and brown adipose tissue. The contribution of these organs to the fetal plasma pool of Ao remains to be determined. However, unlike the adult, the fetal liver may not be the primary source of circulating Ao in the fetus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206910 TI - The renal transport of taurine and the regulation of renal sodium-chloride dependent transporter activity. AB - A model for the beta-amino acid taurine transport is presented to help define the ionic, pH, and voltage requirements for the movement of taurine into the rat proximal tubule brush border membrane vesicle (BBMV). Sodium-(Na+)-taurine symport across the apical surface of the proximal tubule has a highly specific requirement for Cl- and Br-. Active taurine transport operates with a 2 Na+:1 Cl :1 taurine-carrier complex. Complexes like the one required for maximal taurine transport may be pertinent for many other amino acids whose uptake is Na(+) dependent. Renal epithelial cell lines LLC-PK and MDCK were used to define the nature of taurine uptake; they express Na(+)-Cl(-)-taurine cotransport that is inhibited by beta-alanine. The cell lines up- or down-regulate taurine transport in response to changes in the taurine concentration of the medium in a manner similar to that seen in BBMV. The adaptation is present by 12 h and depends on new protein synthesis and protein import to the cell membrane. The role of trafficking in the adaptive response was also explored in brush border vesicles. During dietary surfeit, transporter could be down-regulated and transporters could be shifted back into the microtubule system, resulting in taurinuria. Use of continuous renal cell lines allowed a more mechanistic exploration of intracellular trafficking in the up- and down-expression of the Na(+)-Cl(-) taurine cotransporter. Colchicine appeared to be a more potent inhibitor of the rapid (over hours) adaptive response to a reduction in media and, therefore, intracellular taurine content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206912 TI - Intrarenal angiotensinogen: localization and regulation. AB - Multiple lines of evidence (physiologic, immunohistochemical, and molecular biologic) support the presence of a complete intrarenal renin-angiotensin system (RAS). Localization of angiotensinogen messenger ribonucleic acid (mRNA) within the proximal tubule, together with demonstration of renin and converting enzyme mRNAs within the kidney, provide the most persuasive evidence for local, independent synthesis. Data from a combination of in situ hybridization studies, Northern analysis, and physiologic manipulations lead us to propose that a major site for action of a local RAS is the proximal tubule. There, locally generated angiotensins may regulate sodium reabsorption and urine pH. A variety of factors appear to regulate renal angiotensinogen. For instance sodium depletion increases the expression of renal angiotensinogen (as well as renin mRNA), as does high potassium intake and androgen administration. In pathologic states, such as experimental heart failure, and certain models of hypertension, such as the spontaneously hypertensive rat, expression of renal angiotensinogen mRNA levels is altered. It is proposed that changes in the intrarenal RAS may play a role in the maintenance of homeostasis and in the pathophysiology of various disease states. PMID- 2206913 TI - Molecular cloning and expression of the rat angiotensinogen gene. AB - To identify tissue- and hormonal-specific DNA control cis-elements in the rat gene, we have constructed fusion genes consisting of various lengths of the 5' flanking region of the rat angiotensinogen gene linked to a human growth hormone (hGH) reporter gene and have introduced them into a subclone of rat pancreatic islet tumor cell line (1056A) which expresses the highest level of angiotensinogen mRNA. As a negative control, we have also introduced them into a human choriocarcinoma cell line (JEG-3), which does not express the endogenous angiotensinogen gene. The level of the expression of these fusion genes in these cells was determined by the level of immunoreactive hGH secreted into the culture medium. The expression of angiotensinogen-growth hormone (ANG-GH) fusion genes, pOGH (ANG N-1498/+18), pOGH (ANG N-688/+18), pOGH (ANG N-110/+18), pOGH (ANG N 53/+18), and pOGH (ANG N-35/+18) was 1.0, 1.8, 1.5, 12.0 and 3.0-fold higher, respectively, than the promoterless growth hormone expression vector (pOGH). The addition of dexamethasone (10(-6) M), aldosterone (10(-5) M), and thyroid hormone, L-T3 (10(-7) M), stimulated the expression of pOGH (ANG N-1498/+18) by 4.0-, 2.5-, and 2.0-fold above the control level, respectively. Combination of dexamethasone (10(-6) M), L-T3 (10(-7) M), and ethinyl-estradiol (10(-6) M) stimulated the expression of the pOGH (ANG N-1498/+18) to greater than 10-fold over the control. Ethinyl-estradiol (10(-6) M) or progesterone (10(-6) M) alone had no effect on the expression of the pOGH (ANG N-1498/+18).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206914 TI - Neural control of renal hemodynamics and function during development. AB - This review summarizes our current understanding of the role of the renal sympathetic nervous system during development. Recent evidence suggests that renal innervation appears early during fetal life and may play an important role in promoting cellular development. It has also been observed that renal nerve stimulation decreases renal blood flow and increases renal vascular resistance in fetal sheep, but to a lesser extent than in newborn and adult sheep. Moreover, it has been shown that, contrary to previous findings in adult animals, renal nerve stimulation during alpha-adrenoceptor blockade induces renal vasodilation in fetal and newborn sheep, but not in adult sheep. Recent studies have also demonstrated that renal nerves modulate the natriuretic response to a saline load in newborn lambs and influence sodium reabsorption in near-term fetal sheep. The role of renal nerves and neuronally released norepinephrine on renin secretion in the developing kidney is discussed. Finally, it is suggested that efferent renal sympathetic nerve activity might influence fetal renal hemodynamics during stressful conditions. PMID- 2206917 TI - Endogenous and exogenous eczema. PMID- 2206915 TI - Counterbalance in functional adaptation to ureteral obstruction during development. AB - Renal counterbalance, as described by Hinman in 1923, is the phenomenon of increased function of the intact kidney in proportion to the loss of function resulting from unilateral ureteral obstruction (UUO). In the neonatal guinea pig, chronic partial UUO results in severe vasoconstriction and growth arrest of the ipsilateral kidney. Angiotensin II appears to contribute significantly to the vasoconstriction, and the renin-angiotensin system is also involved in the hemodynamic response of the intact opposite kidney to UUO and to relief of UUO. Immunolocalization of renin following complete UUO in the neonatal rat revealed extension of renin-containing cells along the length of the afferent arteriole in both the obstructed and the intact opposite kidney. The proportion of juxtaglomerular apparatuses with detectable renin and renin messenger ribonucleic acid (mRNA) (identified by in situ hybridization), as well as renal renin content (a measure of active renin), were increased in the obstructed kidney compared with the intact opposite kidney. Chemical sympathectomy by chronic guanethidine administration reduced the total renin mRNA in the obstructed kidney (determined by Northern blot analysis) and prevented the increased renin immunostaining in both kidneys. Thus, renal counterbalance in the developing kidney subjected to UUO is mediated or modulated by the renal nerves and involves marked alterations in gene expression and cellular processing of renin. PMID- 2206918 TI - Endogenous and exogenous eczema. Introduction. PMID- 2206916 TI - Immediate and long-term renal effects of fetal exposure to gentamicin. AB - Aminoglycoside antibiotics, like gentamicin, given to pregnant females cross the placenta and accumulate in the fetal kidney, which, like the adult kidney, was found to be the major site of deposition. In young guinea-pigs whose mothers were given gentamicin during the week following nephrogenesis in the fetus, nephron growth was found to be retarded temporarily. In rats whose mothers were given gentamicin during the period of fetal nephrogenesis, the final number of nephrons was reduced by about 20%. In both cases, renal development was impaired, although the concentration of gentamicin in the fetal kidney was lower than that measured in the kidney of human fetuses whose mothers had received a single injection of aminoglycoside. In rats exposed to gentamicin in utero, cellular damage of the undifferentiated and differentiating renal tissues was observed. It is, there are likely that the oligonephronia observed in animals born of gentamicin-treated mothers resulted from a direct effect of the drug at early stages of nephrogenesis. When gentamicin administration to the mother was prolonged, part of the oligonephronia observed at birth might have also resulted from fetal growth retardation, secondary to adverse effects of the drug on the mother. Providing it was not associated with fetal growth retardation, the presence of high gentamicin concentrations in the fetal kidney at late stages of nephrogenesis did not affect nephron differentiation. Long-term studies of rats born with gentamicin-induced oligonephronia showed that neither the antibiotic still present in kidney several weeks after birth, nor the injuries it caused, prevented renal growth and morphological adaptation of the nephrons to their reduced number.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2206919 TI - Nickel contact allergy and a nickel-restricted diet. AB - More than half of nickel-allergic patients develop secondary eruptions, that is, dermatitis in areas of the skin that are not in obvious contact with nickel plated items. Similar eruptions occur after placebo-controlled oral challenge with inorganic nickel salts. The possible relationship between ingestion of nickel in food and secondary eruptions in nickel-sensitive patients is discussed, making reference to the available literature. Recommendations are given for the management of patients suspected to have nickel dermatitis aggravated by nickel in food. PMID- 2206920 TI - Oral hyposensitization in allergic contact dermatitis. AB - In this review, the concepts of hyposensitization, tolerance and hardening are defined. Studies concerning hyposensitization by different routes of allergen administration are mentioned. The most important studies in humans, as well as in experimental animals, regarding oral hyposensitization are then gone into more thoroughly. The possible mechanisms of hyposensitization are discussed. It is concluded that oral hyposensitization in humans is indeed possible. Furthermore, the reaction is antigen-specific, diminishes quickly, and it is probably the dose administered at a certain moment rather than the total amount of allergens ingested that is crucial when receiving hyposensitization. However, further performed studies do not justify the routine use of oral hyposensitization. PMID- 2206921 TI - Systemically induced (hematogenous) contact eczema. AB - The oral or parenteral application of certain contact allergens may elicit eczematous skin reactions "from the inside" in sensitized individuals; this phenomenon has been called "systemically induced eczema" or "hematogenous contact eczema". Both the clinical morphology and dermatopathology are very similar to classical allergic contact eczema. The distribution of skin lesions is mostly symmetrical and may affect the face or the anogenital area. The pathophysiology involves T-lymphocytes and probably secretion of cytokines similar to the well known phenomenon of "flare-up". The most important contact allergens known to elicit systemically induced contact eczema are metal salts, drugs, phytoallergens and balsam of Peru. After careful diagnosis, a specific allergen avoidance is the basis of prophylaxis and therapy. PMID- 2206922 TI - Psychophysiological aspects of eczema. AB - Anxiety is a personality trait of adult patients with eczema and hyperkinesis commonly found in childhood. Eczema may be precipitated and exacerbated by stress in vulnerable individuals. Eczema, appearing on important body image areas or visible skin areas such as the face, may produce marked reactive depression. Biofeedback techniques, including habit reversal, are useful in management. Chronic intractable eczema may be a sign of impaired parent/child relationships. PMID- 2206923 TI - Food allergy and atopic eczema. AB - As a contributing factor, certain foods can provoke skin lesions in some patients with atopic eczema. In newborns with an increased risk of atopy, exclusive breastfeeding during the first months of life and delayed introduction of solid food seem to inhibit or to retard the manifestation of atopic disease. The pathomechanism of provocation of eczema by food has not yet been elucidated. The frequent finding of specific immunoglobulin E (IgE) antibodies to the offending food items suggests that immediate type allergic reactions may be involved. Furthermore, other allergic or nonimmunologic (pseudo-allergic) mechanisms have to be considered. History taking, skin tests, and radioallergosorbent test (RAST) may provide some information with regard to eliciting food, but these procedures usually are not sufficient to obtain a conclusive diagnosis. Oral challenge tests have to be performed in a controlled manner in order to identify food items that are not tolerated and thus have to be avoided. As most of the patients react only to one or two food items and as these often differ from one patient to another, undirected exclusion diet regimens are unnecessary and unethical. Furthermore, such diets bear the risk of malnutrition and of anaphylactic reactions after reintroduction of allergenic food. Dietary recommendations in atopic eczema have to be based on a careful allergological workup of the individual patient. PMID- 2206924 TI - Histopathology of exogenous and systemic contact eczema. AB - The histopathology of systemic allergic contact dermatitis is usually characterized by spongiosis. A number of other much less common to rare histological findings have also been reported, including erythema multiforme-like eruption, vasculitis, urticaria, and miscellaneous groups. PMID- 2206925 TI - Blindness prevention. Prevalence and causes of blindness and visual loss. PMID- 2206926 TI - Expanded programme on immunization. Changes in the poliomyelitis immunization programme. PMID- 2206927 TI - Dengue in the South Pacific. PMID- 2206929 TI - Measles surveillance in 1988. PMID- 2206928 TI - Acquired immunodeficiency syndrome (AIDS). Proposed WHO criteria for interpreting results from western blot assays for HIV-1, HIV-2, and HTLV-I/HTLV-II. PMID- 2206930 TI - Educators, death, and dying. PMID- 2206931 TI - 1987-1988 Medical Oncology training programs. AB - A continuing survey of Medical Oncology training programs was conducted. In 148 programs, there were 841 trainees. This was an increase in the number of trainees recorded in a 1984 survey (767), with a substantial increase in third-year trainees. Since trainees in combined oncology/hematology programs intend to take the Medical Oncology certifying examination, a continuing output of medical oncologists can be expected. PMID- 2206932 TI - Cigarette smoking patterns in patients after treatment of upper aerodigestive tract cancers. AB - There is a paucity of data on variables predictive of successful smoking cessation in cancer patients. In this questionnaire-based study, we report the smoking status of 75 patients (46 men, 29 women) with head and neck cancer followed for a minimum of 30 months after definitive therapy. Seventy-one percent of the men and 61% of the women who were current smokers at diagnosis stopped smoking subsequent to diagnosis and treatment. Only 29% and 39%, respectively, continued to smoke, most at decreased intensity. Patients with laryngeal cancer were most likely to have stopped (83%). Conversely, patients with oral cavity cancer were most likely to be continuing smokers (66%). In addition, older age, college education, and lighter smoking habits were somewhat predictive of successful cessation. Fear of recurrent disease and physician advice were the questionnaire-listed incentives most often chosen as contributing to success in cessation. The role health professionals can play in counseling cancer patients to stop smoking is stressed. PMID- 2206933 TI - Knowledge of colorectal cancer and use of screening tests among higher-risk persons. AB - Colorectal cancer is a major cause of cancer mortality in the United States, and certain risk factors have been identified. Random samples (N = 893) of residents between 40 and 74 years old in two areas (ie, Long Island, New York and the state of Connecticut) with relatively high rates of colorectal cancer were surveyed by telephone in 1988. Prevalence of certain risk factors for colorectal cancer was estimated, including family history of colorectal cancer and personal history of "ulcerative colitis" and "polyps." Knowledge of dietary risk factors for cancer (ie, cured meat and low fiber intake), daily use of fiber cereals, and frequency of medical checkups did not differ significantly among those in higher-risk groups v other respondents. In multivariate analyses a family history of colorectal cancer was a significant independent predictor of knowledge of the frequency of colorectal cancer relative to stomach cancer, and of ever having heard of a fecal occult blood test, but not of having had an occult blood test or procto(sigmoido)scopy. Persons reporting a history of "ulcerative colitis" had a lower assessment of the curability of colorectal cancer, and the frequency of recent procto(sigmoido)scopic examination was not increased. Findings are discussed with reference to potential educational programs in the primary and secondary prevention of colorectal cancer. PMID- 2206935 TI - Staging: practical wisdom for cancer patient care. PMID- 2206934 TI - A study of the dying process in elderly hospitalized males. AB - The dying process was studied by questioning nurses and next of kin of 40 consecutive patients who died in an acute care Veterans Hospital. Information regarding problems commonly thought important in the dying process was elicited and attempts were made to relate this information to global assessments of quality of life during the preterminal week and quality of the moments surrounding death. Despite long-standing awareness of many of these problems, important pain, respiratory difficulty, mood problems, blunted alertness, stooling problems, urination problems, and oral intake problems each was present in at least 50% of patients. Multivariate analysis did not define a convincing relationship between these problems and global assessments of quality. Responses of nurses and next of kin were similar most of the time, but nurses systematically rated pain as less severe than next of kin and next of kin systematically demonstrated less awareness of urinary and stooling problems than nurses. PMID- 2206936 TI - Malignant melanoma as a model for cancer education and prevention. 1989 Harvey lecture American Association for Cancer Education. AB - Cutaneous malignant melanoma is one of the most rapidly increasing and highly fatal cancers in the world today. Current estimates suggest that 1 in 90-100 Caucasians will develop MM by the year 2000, and 20%-30% will eventually die of the disease. The cause of the epidemic of malignant melanoma is clearly increasing exposure to the sun from lifestyle and clothing habits that have changed over the past 50 years. The disease occurs primarily in preexisting nevi in sun-exposed sites in specific high risk populations who can be, and have been, defined. These are primarily middle- and upper middle-class Caucasians with blue eyes, brown or blonde hair, and fair skin, with predominantly indoor occupations who spend, or have spent, considerable time outdoors in leisure and other activities. The presence of a clearly definable cause (exposure to the sun) in specific risk groups, the ease of early detection by simple means, and the devastating outcome of late diagnosis make malignant melanoma an ideal model for teaching the basic tenets of cancer causation, development, and prevention to the public and professionals alike. PMID- 2206937 TI - Breast cancer staging and the "alert": an educational dilemma. AB - The reports of adjuvant chemotherapy of node-negative breast cancer have provoked controversy and confusion. Introduced by an "Alert" from the National Cancer Institute, the study was erroneously interpreted by the press, patients, and physicians to include all patients with Stage I breast cancer. In fact, the study excluded small cancers for which the receptor assay could not be done, excluded women over 70 years of age, and combined Stage I and II cancers. The analysis did not utilize the established staging system taught to students and physicians and sponsored in part by the NCI. This, and the willingness of physicians to follow such messages without review of the original data, is of concern to educators. PMID- 2206938 TI - Certification for oncology nurses: maturing of a discipline. AB - Certification for oncology nurses shares many similarities with board certification in medicine. Within the specialty of oncology nursing, certification provides one measure of excellence and signals a commitment to oncology nursing practice. Since the beginning of oncology nursing certification in 1986, over 7,200 nurses have become certified. This article describes the certification process for oncology nurses and discusses ways in which physicians can assist in this process. PMID- 2206939 TI - Chemotherapy for advanced bladder cancer: 'Midsummer Night's Dream' or 'Much Ado About Nothing'? PMID- 2206940 TI - The second Bagshawe lecture. Matching basic research to the management of cancer: the view from the other side of the fence. PMID- 2206941 TI - Enhancement of chemotherapy and nitroimidazole-induced chemopotentiation by the vasoactive agent hydralazine. AB - Nitroimidazoles have been shown to be potent sensitisers of certain clinically active chemotherapeutic agents. This process of chemopotentiation has been shown to be hypoxia-mediated. The present studies evaluated whether increasing the level of hypoxia in the tumour tissue, by treatment with the vasoactive agent hydralazine, could modify the chemosensitising ability of nitroheterocyclics. Administering either misonidazole or RSU 1164 before, or hydralazine after, the chemotherapeutic agents melphalan, cyclophosphamide or the nitrosourea CCNU, increased the extent of cell kill in both the KHT sarcoma and RIF-1 tumour. However, even greater enhancements could be achieved when hydralazine was used in treatment protocols in which a nitroimidazole was combined with chemotherapy. For example, a 5.0 mg kg-1 dose of hydralazine given 30 min after melphalan, or a 2.5 mmol kg-1 dose of misonidazole administered 30 min before melphalan, increased, compared to melphalan alone, the resultant tumour cell kill by factors of approximately 1.9 and approximately 1.3, respectively. By comparison, when hydralazine was given after the melphalan plus misonidazole combination, treatment efficacy was enhanced approximately 3-fold compared to melphalan alone. Yet in contrast to the results of the tumour response studies, the inclusion of hydralazine did not increase the bone marrow toxicity associated with the chemotherapeutic agent when used alone or in conjunction with a nitroimidazole. The results, therefore, imply that the addition of hydralazine to the chemotherapy, or chemotherapy-sensitiser protocol, led to a therapeutic advantage. PMID- 2206942 TI - Immunohistochemical detection of major histocompatibility complex antigens and quantitative analysis of tumour-infiltrating mononuclear cells in renal cell cancer. AB - In order to investigate the anti-tumour immune responsiveness of patients with renal cell cancer (RCC), we examined 30 such patients for the degree of expression of major histocompatibility complex (MHC) class I and class II antigens on RCC and the populations of tumour-infiltrating mononuclear cells (TIM). Normal renal tubular cells expressed class I but not class II antigens. Most of the tumour cells expressed class I antigens in 25 (83%) cases, but the proportion of such cells was reduced in five cases, three of which were of granular cell type histologically. Class II antigens were detected in all specimens with class I positivity. Various numbers of TIM were detected in 25 cases, being composed mainly of T cells and a smaller number of macrophages. Examination for the phenotype of T cells showed that CD8-positive cells were the dominant population. B cells were not detected. Quantitative analysis revealed that the numbers of TIM were significantly lower in cases showing class I reduction than in those with normal class I expression. Therefore, it was clear that class I antigens were preserved in RCC cells in most cases. Furthermore, a higher rate of reduction of class I antigens was observed in cases of granular cell type, which has been reported to have a worse prognosis than the clear cell type. The present data suggest that degree of the expression of MHC class I antigen on RCC might influence the host immune responsiveness against it. PMID- 2206943 TI - Efficiency of communication between tumour cells in collagen gel cultures. AB - Mixtures of drug-resistant and drug-sensitive tumour cells growing in 3 dimensional boluses in collagen gel matrix are shown to be effectively coupled so that the response of the mixture is significantly influenced by a subpopulation making up only 1% of the total cells. PMID- 2206944 TI - Enhancement by neurotensin of experimental carcinogenesis induced in rat colon by azoxymethane. AB - The effects of neurotensin on the incidence, number, size, and histology of colon tumours induced by azoxymethane (AOM) were investigated in Wistar rats. Rats were given 10 weekly injections of AOM (7.4 mg kg-1 body weight) and were also given 200 micrograms kg-1 of neurotensin in depot form every other day until the end of the experiment. In week 40, prolonged alternate-day administration of neurotensin resulted in significant increases in the number and size of colon tumours and the incidence of adenocarcinomas penetrating muscle layer and deeper. However, neurotensin did not influence the incidence of tumour-bearing rats and the histological appearance of colon tumours. Administration of neurotensin caused a significant increase in the labelling index of the colon cancers but not that of colon mucosa. These findings indicate that neurotensin enhanced the growth of colon tumours, possibly related to its effect in increasing proliferation of colon cancer cells. PMID- 2206945 TI - Intratumoral induction of tumour necrosis factor by systemic administration of Bordetella pertussis vaccine. AB - Intratumoral induction of tumour necrosis factor (TNF) by administration of Bordetella pertussis vaccine (BPV) as compared with that by the agent OK-432 was investigated in mice. Two hours after such administration tumour tissues tested were resected from the mice, homogenised, and the TNF activities in the homogenate were assayed using a L-929 fibroblast assay. Intravenous injection of BPV into mice bearing the MM46 carcinoma resulted in a greater concentration of TNF in the tumour homogenate than in the serum. With OK-432, however, there was a greater concentration of TNF in the serum than in the tumour homogenates. A high level of intratumoral TNF induction by BPV was also observed in mice bearing Meth A fibrosarcoma or Lewis lung carcinoma. The therapeutic effect against the Meth A fibrosarcoma was in parallel with the intratumoral TNF activity. Intratumoral TNF activity is therefore believed to be a good index of therapeutic effect. PMID- 2206946 TI - Endothelial cell mitogen released from HT29 tumour cells grown in monolayer or multicellular spheroid culture. PMID- 2206947 TI - Changes of AgNORs in HeLa cells during serum starvation. PMID- 2206948 TI - Potential usefulness of quinine to circumvent the anthracycline resistance in clinical practice. AB - Quinine, the widely used antimalaria agent, was found to increase the cytotoxicity of epideoxorubicin (epiDXR) in resistant DHD/K12 rat colon cancer cells in vitro. Quinine appeared as slightly less effective than quinidine or verapamil for anthracycline potentiation but its weaker cardiotoxicity could counterbalance this disadvantage in vivo. Serum from six patients treated by conventional doses of quinine (25-30 mg kg-1 day-1) was demonstrated to enhance the accumulation of epiDXR in DHD/K12 cells as judged by fluorescence microscopy and HPLC assay (1.6 to 6-fold compared with control serum). In this patients quinine concentrations in serum ranged from 4.4 to 10.1 micrograms ml-1. Our results suggest that quinine could be safely used as anthracycline resistance modifier in clinical practice. PMID- 2206950 TI - Effect of megestrol acetate on weight loss induced by tumour necrosis factor alpha and a cachexia-inducing tumour (MAC16) in NMRI mice. AB - The effect of the synthetic progesterone, megestrol acetate, on weight loss induced by both tumour necrosis factor alpha (TNF) as a model for the cachexia accompanying the acquired immunodeficiency syndrome and by a cachexia-inducing tumour (MAC16) has been studied in NMRI mice. Megestrol acetate was effective in preventing weight loss in both model systems with treated animals having an increase in intake of both food and water. Megestrol acetate was unable to prevent loss of body weight in animals pair-fed with TNF treated animals, suggesting that the increase in food and water intake was responsible for the increase in body weight. Analysis of body composition showed that the major contribution to the increase in body weight in animals treated with megestrol acetate was an increase in water content, although there was also an increase in carcass fat in animals bearing the MAC16 tumour given the high dose of megestrol acetate. Animals bearing the MAC16 tumour had a significant increase in tumour weight after treatment with megestrol acetate, possibly owing to the increased plasma glucose levels. These results suggest that an increase in appetite and weight gain alone are not sufficient to justify the anticachectic effect of a particular agent and that body composition analysis and tumour growth rate are very important parameters. PMID- 2206949 TI - Cross-resistance to tumour promoters in human cancer cell lines resistant to adriamycin or cisplatin. AB - The growth inhibitory effect of tumour promoters on human leukaemia and lung cancer cell lines was examined using the [3-(4,5 dimethylthiazol)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The four cell lines used were the K562 human leukaemia cell line, its adriamycin (ADM)-resistant subline (K562/ADM), which shows the mdr phenotype, PC-9 (a human lung adenocarcinoma cell line) and its cisplatin (CDDP)-resistant subline (PC-9/CDDP), which does not show the mdr phenotype. Phorbol 12-tetradecanoate-13-acetate (TPA) and the TPA-type tumour promoters, aplysiatoxin and debromoaplysiatoxin, inhibited the growth of the two parental cell lines, K562 and PC-9. The non-TPA-type tumour promoter, okadaic acid, also inhibited the growth of the two parental cell lines in a dose dependent manner. TPA-type and okadaic acid inhibited the growth of K562/ADM more weakly than that of K562, and showed no growth inhibition in PC-9/CDDP. Anhydrodebromoaplysiatoxin, an inactive derivative of the TPA-type tumour promoter, could suppress the growth of K562 and K562/ADM only at high concentration (more than 50 pM) and it showed similar growth inhibitory effects on the two cell lines. Okadaic acid tetramethyl ether, the inactive form of the non-TPA-type tumour promoter did not inhibit the growth of any of the cell lines. The growth inhibitory effect of these compounds was well correlated with their tumour-promoting activity. A study of the accumulation of okadaic acid revealed that the amount of 3H-okadaic acid in K562/ADM and PC-9/CDDP was similar to that in their parental cells indicating that cross-resistance to this tumour promoter in the drug-resistant cell lines is not due to a difference in the amount of drug accumulated in sensitive and resistant cells. These results suggest the presence of another common mechanism for resistance to ADM and CDDP as well as to TPA- or non-TPA-type tumour promoters. PMID- 2206952 TI - Increasing incidence of adenocarcinoma of the gastric cardia and adjacent sites. AB - Data in a regional cancer registry covering a population of 5 million and with an efficiency of registration of over 95% have been used to examine incidence trends in oesophageal and gastric carcinoma. In the West Midlands Region of the UK, during the period 1962 to 1981 the age standardised incidence of gastric carcinoma decreased by 20%. However, an analysis by both histological type and detailed site reveals that while the incidence of distal lesions is diminishing, the incidence of adenocarcinoma of the oesophagus and cardia is increasing. The proximal and distal lesions also exhibit marked differences in social class distribution and sex ratio. The results strongly suggest that the aetiological factors involved for cardia and adjoining sites are different from those for pyloric antrum. PMID- 2206951 TI - 4, 6-0-benzylidene-D-glucopyranose (BG) in the treatment of solid malignant tumours, an extended phase I study. AB - 4, 6-0-Benzylidene-D-glucopyranose (BG), a derivative of benzaldehyde (BA), whose anti-tumour action has often been reported, showed responses in 10 out of 24 patients (41.7%). These patients consisted of 11 cases of primary lung cancer, 4 of metastatic lung cancer, 5 of gastric cancer, and one each of cancer of the sigmoid colon, liver, pancreas and prostate. There were two complete responses (one each of ipsilateral lung metastasis from breast cancer and metastatic liver lesions due to gastric cancer). The mean total dose of BG was 392.6 g, given by intravenous infusion of 1.2 g BG in 100 ml saline twice daily. The treatment was discontinued when no response was observed after two months. Careful monitoring showed no toxic action of BG at these large doses. Complete necrotic liquefaction of tumour, without any damage to surrounding tissue, was seen in 2 of 3 cases in which histological examination was feasible. It is apparent that BG, like BA, is not a cytotoxic agent in the ordinary sense, but its mechanism of action is still unknown. PMID- 2206953 TI - Serum oestrogen levels in postmenopausal women: comparison of American whites and Japanese in Japan. AB - Serum oestrone (E1), oestradiol (E2) and sex hormone binding globulin (SHBG) levels were studied in postmenopausal Japanese women in Japan (n = 91) and postmenopausal American white women (n = 38). The Japanese women were deliberately chosen to be from a rural agricultural area in order to get samples which represent as closely as possible the traditional Japanese 'lifestyle' that gave rise to the low rates of breast cancer in Japan. E1 levels were 47%, and E2 levels 36%, greater in the American women; these differences were only reduced to 43% and 27% after adjustment for the lower weight of the Japanese. These results were all statistically highly significant. There was little difference in SHBG levels between the Japanese and the American women. These results for E1 and E2 could be an important part of the explanation why Japanese and American breast cancer rates continue to diverge further after the menopause. PMID- 2206954 TI - High dose cytosine arabinoside in the initial treatment of adults with acute lymphoblastic leukaemia. AB - In a study conducted at St Bartholomew's Hospital between 1972 and 1982, using moderately intensive therapy (OPAL/HEAV'D), a low blast count at presentation (less than 10 x 10(9) 1(-1)) and common ALL (C-ALL) phenotype correlated favourably with duration of remission. Fifty-four patients (age range 15-57, median 32) subsequently received a modification of the previous treatment programme which included high-dose ara-C 2 g m-2 b.d. for 6 days as cycle 3 (OPAL + HD ARA-C). CR was achieved in 36/54 (67%) patients, response correlating favourably with younger age (15-30 years vs 31-57 years, P = 0.02). Three patients died in CR. Overall, there was no difference in survival or remission duration between patients who received high dose ara-C and those in the control group. However, in contrast to the early results, there was a reversal in the relevance of the prognostic factors with a trend in favour of high blast count (greater than 10 x 10(9) 1(-1)) and T-cell phenotype in terms of remission duration. Moreover, comparison of duration of remission for the previously defined prognostic groups according to therapy suggests that the prognosis of patients with 'high risk' disease (T, B, null ALL or high blast count) is improved with more intensive therapy. In contrast, those with 'low risk' disease (C-ALL and low blast count) have a better prognosis with less intensive therapy. These observations confirm those of others and allow for individualization of therapy on the basis of pre-treatment variables. PMID- 2206955 TI - Urinary epidermal growth factor (hEGF) levels in patients with carcinomas of the breast, colon and rectum. AB - A specific two-site ELISA for human epidermal growth factor (hEGF) has been used to measure urinary hEGF/creatinine ratios in 30 normal subjects, 30 hospital in patients with breast cancer and 30 hospital in-patients with colonic or rectal cancer. There was no significant difference between patients with breast cancer and controls. Although a statistically significant difference between patients with colorectal cancer and controls was observed, the biological significance of this observation is doubtful. No clear effect of the presence of breast or colorectal carcinoma on the urinary excretion of hEGF has been observed. PMID- 2206956 TI - Assessment of milk fat globule membrane antibodies and lectins as markers of short-term prognosis in breast cancer. AB - The milk fat globule membrane antibodies HMFG1, HMFG2, NCRC 11 and four of the Mam 6 series, and the lectins peanut agglutinin, wheat germ agglutinin, Concanavalin A, Lotus tetragonolobus and Ulex europaeus I have been applied to 115 stage I and II breast carcinomas (median follow up = 36 months) to assess their value as prognostic markers. Of the milk fat globule membrane antibodies only NCRC 11 staining showed a relationship to development of recurrent disease and overall survival, but this did not act as an independent indicator over and above that provided by histological grade. None of the lectins gave prognostic information, including those whose binding related to node status or grade. It is concluded that for short-term prognosis none of the markers can given independent prognostic information over and above that provided by histological evaluation. PMID- 2206957 TI - The cost of folinic acid. PMID- 2206958 TI - Breast cancer and combined oral contraceptives. PMID- 2206960 TI - 31st annual meeting of the British Association of Cancer Research and the 5th annual meeting of the Association of Cancer Physicians. 19-22 March 1990, Sussex, UK. Abstracts. PMID- 2206959 TI - 24th Paterson Symposium. Cellular interactions in differentiation and neoplasia. 12-15 November 1989. PMID- 2206961 TI - Nottingham international breast cancer meeting. 26th-28th September, 1990, Nottingham. Abstracts. PMID- 2206962 TI - Fast-scan magnetic resonance: principles and applications. PMID- 2206963 TI - Abnormal vowel patterns in phonological disorder: some data and a hypothesis. AB - This article examines the vowel systems of a group of phonologically disordered children who show abnormalities in their vowel patterns. The conclusions emerging from the analysis of disordered speech are presented, along with examples from the data. It is argued that there are relatively common context-free processes of simplification of the vowel system in the data, and that these represent natural changes that may occur in normal development. Other less common processes may be idiosyncratic, and indicate some measure of disordered development. Some difficulties with vowels may relate to difficulties in the consonant system, or to difficulties with prosodic or paralinguistic features. Variability is an important part of the data, relevant to understanding the disorder and the process of development. It is hypothesised that the proposed framework will be relevant to clinical decision-making. PMID- 2206964 TI - Syntactic comprehension in children with expressive language impairment. AB - Two groups of language-impaired children, an 'expressive language impairment' group and a 'development dyspraxic' group, aged between 4 and 6 years, were assessed on a set of test sentences designed to tap syntactic comprehension. Expressive language was profiled for both experimental groups. A control group completed the syntactic comprehension test only. The results indicate that children with apparently isolated defects of expressive syntax do, in fact, have subtle deficits of comprehension in comparison to age-matched controls. The deficit can be detected in a syntactic decoding task. Comprehension strategies used by this group are examined. The 'dyspraxic' group did not perform significantly differently to controls. PMID- 2206965 TI - Language development at 3 years in pre-term children of birth weight below 1000 g. AB - Language development at 3 years of pre-term children born below 1000 g birth weight was compared with full-term controls matched for social background. The pre-term group used less complex expressive language and showed lower receptive understanding, auditory memory and verbal reasoning. Language outcome was related to intraventricular haemorrhage but not to global indication of postnatal illness such as number of days on the ventilator. Average verbal intelligence in environmentally low risk, extremely low birth weight children is an insufficient indicator of complex language functioning. PMID- 2206966 TI - Speech therapy and Parkinson's disease: a review and further data. AB - A review is undertaken of recent experimental studies of the effects of speech therapy offered to patients with Parkinson's disease. In contrast to earlier opinions based upon clinical impressions, the results of these studies indicate that the immediate gains from therapy measured within the clinical setting are readily detected, that these are perceived by patient's relatives and that there is reasonable evidence that benefits persist for some period after treatment. A further study is reported which tests the effects of a less intensive treatment regimen. This also gave positive results. Although questions remain regarding the most efficient form of treatment and the extent of its benefits outside the clinic, the existing results warrant greater optimism about the benefits of speech therapy offered to patients with Parkinson's disease. PMID- 2206967 TI - The use of hypnosis in speech therapy: a questionnaire study. AB - Speech therapists trained in the use of hypnosis were asked to identify the client groups with whom hypnosis was used and the main benefits of hypnosis in the management of these clients. Thirty-six (42%) of the questionnaires produced usable data. The majority of respondents use hypnosis in the treatment of voice or fluency disorders although hypnosis is used in the treatment of acquired neurological disorders too. Respondents were less inclined to use hypnosis with children than with adults. The major use of hypnosis in fluency and voice disorders is as a means of achieving relaxation and of encouraging self-esteem in the client. Of respondents 87% use autohypnosis. Problems encountered in the use of hypnosis and autohypnosis are explored. The results suggest that a closer examination of the purpose and efficacy of hypnosis is called for. PMID- 2206968 TI - Effect of topical retinoic acid on the interleukin 1 alpha and beta immunoreactive pool in normal human epidermis. AB - The topical application of 0.1% retinoic acid (RA) on human skin over a period of 4 days, whether or not under occlusion, did not increase either IL-1 alpha or beta immunoreactivity as determined by a sensitive enzymoimmunoassay. No down modulation was seen following the application of a potent topical corticosteroid. Occlusion increased the yield of IL-1 beta immunoreactivity. Immunoblot patterns of epidermal extracts revealed both the mature form of IL-1 (17 kDa) and the precursor (36 kDa) and were identical in amounts whether the specimens were from controls or from RA- or corticosteroid-treated skin. There was a slight modification in the pattern of high molecular weight proteins (52 kDa) probed by the anti-IL-1 alpha and beta sera. It appears that the IL-1 epidermal immunoreactive pools are barely amenable to modulation because they represent a storage form linked to end-stages of keratinocyte differentiation. PMID- 2206969 TI - Skin exudate levels of interleukin 6, interleukin 1 and other cytokines in mycosis fungoides. AB - The role of locally released cytokines in inducing lymphocyte activation and infiltration in the skin lesions of mycosis fungoides has been investigated. The levels of selected cytokines were measured in chamber fluid samples from lesional and control skin. Biologically active interleukin 6 was significantly elevated in lesional samples and a recombinant form of this cytokine was shown to induce lymphocyte migration in an in vitro assay. Biologically active interleukin 1 was detected in all control chamber fluid samples. Significantly reduced levels of this cytokine were present in lesional samples, which may be the result of the release of preformed material. Interleukin 2 and tumour necrosis factor activity, and gamma interferon and granulocyte macrophage colony-stimulating factor immunoreactivity, were not detectable in any of the samples. Interleukins 1 and 6 may play a role in the pathogenesis of the lesional lymphocyte infiltrates in mycosis fungoides. PMID- 2206970 TI - Elastic fibre damage induced by low-dose D-penicillamine. AB - We have studied 23 patients receiving penicillamine for the treatment of rheumatoid arthritis to determine the prevalence of penicillamine-induced elastosis. One female patient had pseudoxanthoma elasticum-like skin changes and bramble-bush elastosis without calcification in the involved skin. Penicillamine elastosis was present in the joint capsule in 62% of eight patients or 64% of II joints examined and was detected in joint capsules after as little as I year of treatment. PMID- 2206971 TI - Invasive migration of epidemic Kaposi's sarcoma cells in vitro. AB - Kaposi's sarcoma (KS) is a low grade malignant neoplasm which shows invasive growth and often occurs in immunosuppressed patients with the Acquired Immune Deficiency Syndrome (AIDS; epidemic KS). It is also found in elderly men where it is usually limited to the skin (classic KS). The present study investigated the chemotaxis and invasive migration of epidemic KS cells in vitro and compared them to cells grown from classic KS lesions and to fibroblasts. Epidemic KS cells demonstrated invasive migration through reconstituted basement membrane (Matrigel) as well as through interstitial connective tissue (collagen I) in early passages, whereas fibroblasts did not invade either barrier. Epidemic KS cells in late passages did not show any invasive migration. Following pretreatment with tumour necrosis factor alpha (TNF-alpha) there was no enhanced migration through the Matrigel and collagen I for epidemic KS cells, whereas classic KS cells showed an increased migration through the type I collagen barrier. PMID- 2206972 TI - Pentoxifylline inhibits the proliferation of human fibroblasts derived from keloid, scleroderma and morphoea skin and their production of collagen, glycosaminoglycans and fibronectin. AB - Pentoxifylline, an analogue of the methylxanthine theobromine, inhibits the proliferation and certain biosynthetic activities of fibroblasts derived from normal human skin. Fibroblasts from the skin of patients with keloids, scleroderma and morphoea were cultured in vitro in the presence and absence of pentoxifylline (100-1000 micrograms/ml) to determine whether it inhibits fibroblast proliferation and the production of collagen, glycosaminoglycans (GAG), fibronectin and collagenase activity. The exposure of subconfluent fibroblast cultures to pentoxifylline resulted in non-lethal, dose-dependent reductions in serum-driven fibroblast proliferation, with 1000 micrograms/ml pentoxifylline virtually negating the proliferative effect of serum on the cells. The fibroblasts assayed as confluent cultures produced reduced amounts, by up to 95%, of collagen and GAG, dependent on the concentration of pentoxifylline, both in the presence and absence of serum. Pentoxifylline similarly inhibited the fibronectin production by keloid and scleroderma fibroblasts, but had no effect on collagenase activity. PMID- 2206973 TI - Analysis of side-effects of medium- and low-dose cyclosporin maintenance therapy in psoriasis. AB - The side-effects of long-term cyclosporin A (CyA) treatment in 26 patients with severe psoriasis were evaluated. These patients had a mean PASI score of 30.2 and were treated with CyA for between 7 and 37 months (mean 19.5 months). There were three groups according to the dose of CyA, less than 2 mg/kg per day, 2-3 mg/kg per day and greater than 3 mg/kg per day. In all three groups, CyA was found to be equally effective. Treatment with CyA was discontinued in 12 of the 26 patients because of nephrotoxicity and/or development of hypertension. One was in the less than 2 mg/kg per day group, three were in the 2-3 mg/kg per day group and eight in the greater than 3 mg/kg per day group. There was no hepatotoxicity with CyA treatment. One patient developed two squamous cell carcinomas of the skin. PMID- 2206974 TI - Ultrasound velocity in human fingernail and effects of hydration: validation of in vivo nail thickness measurement techniques. AB - Distal nail thickness was measured using an electronic micrometer and both distal and proximal nail ultrasound times were recorded in 20 volunteers (10 male, 10 female), aged 20-39. The fingernail ultrasound velocity was 2.26 X 10(3) m/s (subject range 2.03-2.69) (analysis of variance technique). The proximal ultrasound transit time was greater than distal ultrasound transit time. In three volunteers, five micrometer and one distal midline ultrasound measurement of five nails were repeated on 10 occasions over 2 weeks. For the micrometer readings the average coefficient of variation was 5.3% (SD +/- 2.4%), and for the ultrasound reading the average coefficient of variation was 4.0% (SD +/- 1.3%). To assess the influence of hydration, in five volunteers the distal nail micrometer thickness and the distal nail ultrasound transit time were measured on five nails before and after 30 min of immersion in water initially at 37 degrees C. The mean distal ultrasound transmission time increased from 0.20 +/- 0.04 microseconds to 0.22 +/- 0.04 microseconds (P less than 0.001) after water immersion. The micrometer measurements and ultrasound velocity did not change significantly (mean ultrasound velocity = 2.01 X 10(3) m/s before, 2.04 X 10(3) m/s after immersion). PMID- 2206975 TI - Effects of haem arginate on variegate porphyria. AB - Four patients with variegate porphyria (VP) were treated with repeated haem arginate infusions daily for 4 days and then weekly for 4 weeks. After the initial four daily doses of haem arginate (haem 3 mg/kg), the excretion of faecal protoporphyrin (mean 579 nmol/g dry wt) fell to an almost normal level (mean 123 nmol/g dry wt), and that of coproporphyrin (mean 162 nmol/g dry wt) to the normal level (mean 21 nmol/g dry wt) in all patients. However, during the period of the four weekly infusions of haem the excretion of porphyrins increased almost to the pretreatment level. Phototesting showed no changes in the photoreactivity of the skin, and no improvement in skin lesions was seen during the treatment. Except for one case of thrombophlebitis no side-effects occurred. In a child with homozygous VP, four daily infusions of haem arginate (2 mg/kg) normalized the faecal protoporphyrin content, but had no effect on the increased erythrocyte protoporphyrin concentration. PMID- 2206976 TI - Successful treatment of eruptive pyoderma gangrenosum with intravenous vancomycin and mezlocillin. PMID- 2206977 TI - Skin manifestations in congenital deficiency of leucocyte-adherence glycoproteins (CDLG). AB - In congenital deficiency of leucocyte-adherence glycoproteins (CDLG) there is an immunodeficiency with impaired leucocyte function and cutaneous and extracutaneous infections occur. In more than 30% of cases the condition has a fatal course. We report the skin manifestations of three siblings with CDLG in which areas of skin necrosis occurred that resembled pyoderma gangrenosum. PMID- 2206978 TI - An unusual case of acquired localized argyria. AB - We report an unusual cause of localized cutaneous argyria, due to the cutaneous implantation of a silver earring back. PMID- 2206979 TI - Granulomatous cheilitis and Crohn's disease. PMID- 2206980 TI - Kawasaki disease in a young adult with a perineal rash. PMID- 2206981 TI - Aquagenic pruritus and the myelodysplastic syndrome. PMID- 2206982 TI - Persistent vitiligo induced by diphencyprone. PMID- 2206983 TI - Target cell toxicity of inhaled spermidine in rat lungs. AB - Rats were exposed for a single 6-h period to varying concentrations of aerosols of the polyamine, spermidine trihydrochloride. They were subsequently killed at 6 h, 1, 2, 5, 9 and 14 days after the start of exposure. The lungs were examined for histopathological alterations at both light and electron microscopic level and assays of lung spermidine burdens performed. In rats killed at the 6-h termination period, lung spermidine levels had increased approximately 1.5-fold although concentrations in animals killed on days 1 and 2 showed only marginal increases. Concentrations peaked again on day 5 and henceforth decreased until control spermidine levels were again achieved on day 14. Exposure of rat lungs to spermidine resulted in a specific dose-dependent necrosis of Clara cells of the bronchiolar epithelium and alveolar Type II cells. At the lowest dose used (6 mg/m3) specific necrosis of the Clara cells was seen at the earliest time interval studied, i.e. 6 h, but these cells were rapidly lost and subsequently replaced without evidence of significant cell proliferation by the 2-day sacrifice period. At all higher dose levels additional necrosis of the alveolar Type II cells occurred which was not reversible but which progressed through alveolitis to a fully developed subchronic pneumonitis by 14 days. PMID- 2206984 TI - Rickets induced by calcium or phosphate depletion. AB - We studied the effects of calciopenia and phosphopenia on longitudinal growth, skeletal mineralization, and development of rickets in young Sprague-Dawley rats. At an age of 21 days, two experimental groups were given diets containing 0.02% calcium or 0.02% phosphorus; otherwise the diets were nutritionally adequate. After 7, 14, and 21 days, five animals from each group were randomly chosen. The animals were anaesthetized and blood samples were drawn for analysis of calcium, phosphorus, and immunoreactive parathyroid hormone, whereupon the animals were killed. Length, weight, and specific weight of the left femur were measured. After 28 days on the respective diet the remaining animals were killed and one proximal tibia from each animal was processed for light microscopy and subjected to stereological analysis. Both experimental groups developed progressive growth retardation, more so the phosphate-depleted group. The calciopenic animals developed severe hypocalcaemia and secondary hyperparathyroidism, whereas the phosphate-depleted animals, in spite of marked secondary hypercalcaemia, had unaltered levels of immunoreactive parathyroid hormone. By 28 days both experimental groups displayed rachitic changes, more pronounced in the phosphate depleted animals. This paper provides quantitative data demonstrating that calciopenia per se may cause rickets in young rats, but that the rachitic changes in this condition are less severe, and the growth pattern different from those in phosphate depletion. PMID- 2206985 TI - The zona glomerulosa of the adrenal gland in rats with portacaval shunt. An ultrastructural and morphometric study. AB - The zona glomerulosa of the adrenal glands was studied histologically, ultrastructurally and morphometrically in portacaval shunt (PCS)-bearing rats 4 weeks after surgery. Compared with controls, the zona glomerulosa of rats with PCS showed an increase in thickness and a reduction in the number of lipid droplets in the cells of its inner portion, adjacent to the intermediate zone. Moreover, electron microscopy and morphometry of the cells of the inner portion revealed that qualitative and quantitative changes occur, consisting in a decrease in lipid droplets, an increase in the amounts of smooth endoplasmic reticulum and mitochondria, enlargement of the Golgi apparatus, and the appearance of numerous dense bodies at the vascular cell poles. All the above findings indicate that PCS induces an enhanced activity of the fully differentiated cells of the zona glomerulosa, which may be considered as an adaptive response--mediated by an activation of the renin-angiotensin system--to the lowering of the systemic pressure taking place in this experimental condition. PMID- 2206986 TI - A morphological comparison of treatment with different beta-lactam antibiotics on experimental staphylococcal endocarditis and aortitis. AB - The effect of treatment of staphylococcal endocarditis and aortitis with five different beta-lactam antibiotics (ceftazidime, cephaloridine, cefotaxime, methicillin and flucloxacillin) was evaluated by light and electron microscopy. It was found that therapy with all five antibiotics produced similar morphological changes. At 3 and 8 h, the bacterial colonies showed zonal changes with the bacteria furthest from the lumen exhibiting less severe damage while the outer region consisted largely of lysed cells. However, in the outer zone a few apparently viable, thick-walled persistent bacteria were observed. At 24 and 48 h, many colonies consisted of large masses of lysed bacteria with only a few thick-walled persistent bacteria. In all cases, therapy was associated with an increased host inflammatory cell response resulting in invasion of leucocytes through the aortic wall or vegetation towards and engulfing the colonies. However, even at 48 h the inflammatory cells had not reached all the deep-seated colonies. It would appear that all the antibiotics reached bactericidal concentrations within the lesions. However, the eradication of the few 'persistent' bacteria was delayed by the inability of the inflammatory cells to reach all the colonies. PMID- 2206987 TI - 2-Bromoethanamine nephrotoxicity in the nude mouse: an atypical targetting for the renal cortex. AB - Male MF1-nu/nu/Ola/Hsd nude mice, maintained in a gnotobiotic environment, were dosed i.p. with either 50, 100 or 200 mg/kg 2-bromoethanamine (BEA) hydrobromide to induce a model papillary necrosis. Renal histological changes were examined in semithin glycolmethacrylate resin sections at 24, 48 and 72 h after BEA treatment. The sequence of medullary changes included pyknosis of interstitial cell nuclei, increased staining of the interstitial mucopolysaccharide matrix, platelets adhering to capillary endothelium, necrosis of collecting duct epithelial cells and denudation of the covering epithelium of the papilla. This was similar to that previously described in the Wistar rat, but the time course was extended. There was also a concomitant and extensive cortical necrosis of the P2 and P3 segments of the proximal tubule, which was evident prior to the onset of renal papillary necrosis at the higher doses of BEA. Nude mice show an atypical response to BEA compared to several mouse and rat strains, the hamster and pig, that suggests unique characteristics in this athymic murine mutant. PMID- 2206988 TI - Serum lipoproteins during bone marrow hyperplasia after phenylhydrazine administration in rats. AB - In the present study, lipoprotein metabolism was investigated during compensatory hyperplasia of bone marrow after haemolysis induced by phenylhydrazine (20 mg/kg b.w.) administration in rats. The rats were sacrificed at different time intervals (0, 1, 2 and 5 days) after phenylhydrazine treatment. Analysis of the different fractions of lipoproteins has shown that during bone marrow hyperplasia there is an alteration of lipoprotein profiles, mainly due to a decrease of HDL2 and HDL3 subfractions. PMID- 2206990 TI - Mode of transmission and histology of M. leprae infection in nude mice. AB - Athymic (nude) mice were experimentally infected with Mycobacterium leprae via the alimentary and respiratory tracts and through the skin. Animals were allowed to inhale aerosols of M. leprae or had bacilli instilled into the nostrils or directly into the lungs. Others were fed M. leprae by gastric tube or had bacilli placed on the tongue. Attempts were also made to transmit M. leprae from infected footpads by Aedes aegyptii mosquitoes. The most successful infections resulted from nasal instillations and from bacilli inoculated onto the tongue surface: in these cases heavy systemic infections occurred. M. leprae was also shown to survive passage through the alimentary tract and bacilli recovered from the faeces were capable of causing infection in recipient nude mice. The possible epidemiological significance of these findings for the transmission of leprosy in man is discussed. PMID- 2206989 TI - Ultrastructural features of diethylnitrosamine-induced lesions in the mouse liver. AB - Mice were given a single dose of diethylnitrosamine (DEN). After 12 and 15 months, the ultrastructural features of simple hepatic nodules and defined hepatocellular carcinomas were compared. The main difference between these two lesions is the presence of highly convoluted membranes in the hepatocytes of the carcinomas. A third population of nodules was also found which could not be easily classified at the light microscope level into either simple hepatic nodules or carcinomas. Ultrastructural examination of these lesions showed them to have areas resembling both simple hepatic nodules and carcinomas. Within both these areas hepatocytes with convoluted plasma membranes were observed. Changes in membrane pattern may be indicative of an altered cell growth pattern and the acquisition of invasive or metastatic properties. This provides further evidence suggesting that a sub-population of cells can be identified which has the potential to develop into overt carcinoma. PMID- 2206991 TI - Primary biliary cirrhosis in the mouse: induction by human mycoplasma-like organisms. AB - Human intraocular and orbital chronic inflammatory disease with autoimmune features has been reported to be caused by mycoplasma-like organisms (MLO). MLO are intracellular cell-wall deficient pathogenic bacteria, closely related to rickettsia, with a characteristic ultrastrural pleomorphic tubulo-spherical and filamentous appearance. No culture system has been developed for MLO and diagnosis of MLO disease is made by detecting these bacteria within infected cells using a transmission electron microscope. In human MLO ocular and orbital disease the organisms are found in parasitized leucocytes at the disease site. Inoculation of human MLO into mouse eyelids produces a high incidence of orbital and introcular disease. MLO disseminate to produce randomly distributed lethal systemic disease with infected leucocytes found in all disease sites and with similar histologic features in all disease sites. Microvasculitis is the initial lesion. Disease progression results in lysis of vascular and parenchymal structures, stromal lymphocytic infiltrates, granulomas, and fibrosis. This report describes the hepatic portal chronic progressive inflammatory disease in 11 of 100 of those mice versus 0 in 200 controls. MLO parasitized portal leucocytes are present in all 11 inflamed livers versus 0 in 5 control livers (P less than 0.05). The resemblance of the animal liver disease induced by MLO to human primary biliary cirrhosis and rifampin treatment of MLO disease are discussed. PMID- 2206992 TI - Experimental frost-bite in Hanford Miniature Swine. III. Sweat gland changes. AB - Frost-bite was produced in five Hanford Miniature Swine by exposure to -75 degrees C air for 1, 3, 5, 10 or 20 min. Biopsies were taken at 0, 3, 6, 12, 24 and 48 h and 1, 2 and 15 weeks. Sweat glands were evaluated microscopically and graded: 0, no change to 5, severe change. Sweat gland changes were mild by 1 h and moderate by 24 h for all freeze groups, except the 1-min freeze group. Severe morphological changes were of two types: degeneration/necrosis and squamous metaplasia. These changes suggest that hyperhidrosis, as a sequel to frost-bite, may be more subjective than real and that squamous cell carcinoma, as a delayed sequel to frost-bite, could originate from sweat glands as well as from the epidermis. PMID- 2206994 TI - The role of the bcl-2 gene in lymphoma. PMID- 2206993 TI - Does allopurinol prevent myocardial injury as a result of hypoxia-re-oxygenation in rats? AB - We made use of the xanthine oxidase inhibitor allopurinol and examined changes related to myocardial injury of the rat heart during hypoxia-re-oxygenation. The rat heart was perfused using the Langendorff method. With low-oxygen perfusion for 60 min in a solution saturated with mixed gases of 95% N2 + 5%O2, contractile tension did not develop and tension development was not restored upon re oxygenation. During hypoxia, the resting tension increased (4.1 g) in the absence of allopurinol. In the allopurinol-administered group (100 microM), contractile tension did not develop during hypoxia; however, the development of tension was restored (18%) upon re-oxygenation. The elevation of resting tension was less (3.2 g) during hypoxia. All events related to the myocardial injury (inhibition of Na+, K(+)-ATPase activities, generation of malondialdehyde, extracellular leakage of creatine kinase) after low-oxygen perfusion for 60 min and re oxygenating perfusion for 30 min were mild in the allopurinol treated group, compared with findings in the non-administered group. Tissue ATP at 10 min after low-oxygen perfusion was of a significantly high value in the allopurinol treated group (13.2 mumols/g dry weight), compared with findings in the group not given the drug (8.4 mumol/g dry weight). Sixty minutes after low-oxygen perfusion, tissue ATP in the allopurinol group also remained high, compared with the group not given the drug. Although the intensity of the epicardial NADH fluorescence indicated that the extent of inhibition of aerobic energy production during 10 min of low-oxygen perfusion was the same for both groups, lactate was produced in large quantities in the allopurinol treated group, hence energy generation advanced with glycolysis. These observations suggest that allopurinol prevents myocardial injury as a result of hypoxia-re-oxygenation. In the low-oxygen perfusion period, generation of energy is maintained and improved with glycolysis and there is a reduction in the generation of free radicals and an inhibition in lipid peroxidation. PMID- 2206995 TI - Frequencies of common beta-thalassaemia alleles among different populations: variability in clinical severity. PMID- 2206996 TI - Interleukin 5 activity in sera from patients with eosinophilia. AB - Sera from 10 patients with eosinophilia contained eosinophil colony stimulating factor (Eo-CSF) activity. Using anti murine (m) interleukin-5 (IL-5) antibody, we demonstrated that this activity was mainly derived from IL-5. Administration of prednisolone to patients decreased both Eo-CSF activity in sera and the number of eosinophils in blood. These results extend our recent study demonstrating that T cells from eosinophilic patients produce IL-5 with IL-2 stimulation and may support the speculation that IL-5 is an important factor which induces eosinophilia. PMID- 2206997 TI - Effect of recombinant human erythropoietin on anticancer drug-induced anaemia. AB - Anaemia was induced in rats with fluorouracil (5-FU) or cisplatin (CDDP) and the mechanisms of anaemia induction were analysed. Furthermore, the therapeutic effects of recombinant human erythropoietin (rHu Epo) on these anticancer drug induced anaemias were investigated. In 5-FU-induced anaemia, marked serum erythropoietin (Epo) elevation was observed in inverse correlation to blood Hb concentration and Hb concentration rapidly recovered to normal levels. On the other hand, in CDDP-induced anaemia, serum Epo elevation was modest and the lowered Hb concentration persisted longer. Treatment with rHu Epo significantly improved both anticancer drug-induced anaemias but rHu Epo was more effective on CDDP-induced anaemia. These results suggest that rHu Epo might be useful for the therapy of anaemia associated with anticancer chemotherapy. PMID- 2206998 TI - Chromosome and bcr rearrangement in chronic myelogenous leukaemia and their correlation with clinical states and prognosis of the disease. AB - Among 77 unselected patients with chronic myelogenous leukaemia (CML), 70 had Philadelphia chromosome (Ph1) in blood cells. Extra chromosomal abnormalities were noted in 4%, 55% and 78% of Ph1-positive patients in chronic phase, accelerated phase and acute blast crisis, respectively. Rearrangement of the bcr was detected in 46 of 47 Ph1-positive patients studied and also in three of five Ph1-negative ones. The locations of the breakpoints were mapped to one of four zones of the bcr in 45 patients. The median duration from diagnosis of CML to onset of acute blast crisis was not significantly different between the two groups of patients with breakpoints in the 5' portion (34 months), and in the 3' portion (39 months) of the bcr. In addition, the locations of the breakpoints within the bcr did not change as the disease progressed in the six patients who had DNA analysed both in the chronic phase and subsequently in transformation. In one of them, an additional aberrant band which was not present in the beginning of the acute phase was detected in blood cells taken 2 months later. It is suggested from the studies that transformation of CML may not be related to alterations within the bcr. PMID- 2206999 TI - Contrasting patterns of neoplastic cell behaviour in long-term culture of bone marrow from patients with acute leukaemia and myelodysplastic disorders. A survey of responses in 31 cases with cytogenetic determination of neoplastic status of cultured cells in 17 studies. AB - Alterations in neoplastic cell behaviour responsible for increased production of terminally-differentiated granulocytes during long-term culture of bone marrow in different categories of acute leukaemia and myelodysplasia have been investigated. An increase in neutrophils associated with transition to a morphological picture identical to normal control cultures occurred in 15 of 25 studies on acute leukaemia in contrast to one of six studies on myelodysplastic disorders. An abnormal neoplastic karyotype was employed as a marker for monitoring the course of the neoplastic cell population in 11 studies in which there was progression towards a normal pattern of differentiation. An increase in differentiation was shown by this means to represent increased maturation of cells of the neoplastic process in one study on a myelodysplastic disorder, demonstrating domination of proliferative activity in culture by all of the myelodysplastic disorders examined. Transition towards normal differentiation in nine studies on acute leukaemia, however, correlated with partial or complete replacement of the acute leukaemic cells by normal haemopoietic series in de novo acute leukaemia, and by Ph positive cells in blast crisis of CML. Conversion to morphologically and cytogenetically normal cell populations in five studies on de novo acute leukaemia occurred in four cases which failed to respond to remission induction therapy, suggesting the selective toxic effect capable of purging acute leukaemic cells from bone marrow operated by a mechanism which lacked cross resistance to currently-employed cytotoxic agents. PMID- 2207000 TI - Type II oestrogen binding sites in acute lymphoid and myeloid leukaemias: growth inhibitory effect of oestrogen and flavonoids. AB - The presence of oestrogen receptors (ER) and type II oestrogen binding sites (type II EBS) have been investigated by a whole cell assay in seven cases of acute lymphoid leukaemia (ALL) and 16 cases of acute myeloid leukaemia (AML). ER were detected in 6/7 ALL patients with values ranging between 133 and 2268 sites/cell and in 12/16 AML patients with values ranging between 274 and 4197 sites/cell. The apparent dissociation constant (KD) for ER was 0.6 +/- 0.3 nM (mean + SD of 20 cases). All blasts from ALL and AML patients expressed type II EBS at variable levels ranging between 3109 and 239450 sites/cell. The mean KD value for these sites was 18.3 +/- 5.6 nM (mean +/- SD of 23 cases). Specificity experiments demonstrated that type II EBS are oestrogen specific relative to the class of steroid hormones. In addition, the flavonol quercetin was able to compete for [3H]17 beta-oestradiol (E2) binding to type II EBS, the relative binding affinity (RBA) of quercetin being greater than that of diethylstillboestrol (DES). DES and quercetin exerted a dose-dependent inhibition of ALL and AML blast proliferation in the range of concentrations between 10(-8) and 10(-5) M. The RBA of DES and quercetin for type II EBS correlated well with their potency as cell growth inhibitors. Moreover, the flavonols rutin and hesperidin which compete slightly for [3H]E2 binding to type II EBS, were scarcely effective in inhibiting leukaemic cell proliferation. The inhibitory effect of DES and quercetin was not due to a non-specific cytotoxic action since after a 1 d culture period, cell viability did not vary between control and treated cells, being greater than 80%. Our results suggest that high oestrogen concentrations and the flavonol quercetin may inhibit leukaemic blast proliferation through a common mechanism involving a binding interaction with type II EBS. PMID- 2207001 TI - Testicular irradiation in childhood lymphoblastic leukaemia. Medical Research Council Working Party on Leukemia in Childhoods. AB - The effect of randomly allocated testicular irradiation on the subsequent incidence of testicular infiltration and disease-free survival was assessed in two Medical Research Council Childhood Leukemia Trials. UKALL VI and UKALL VII. None of the 83 boys who actually received testicular radiotherapy subsequently developed gonadal disease. whereas 18 of the 163 who were not irradiated did. Despite this there is no apparent difference in disease-free survival for those randomized to receive testicular irradiation compared to those who were not, after a minimum of 8 years follow up. Although prophylactic testicular irradiation appears to prevent subsequent gonadal relapse there is no evidence that it improves overall prognosis when adequate systemic chemotherapy is used. As it has considerable long-term side effects it cannot be recommended as routine therapy. PMID- 2207002 TI - Clinicopathological diagnosis and treatment of malignant histiocytosis. AB - The diagnostic findings of malignant histiocytosis (MH) were analysed in 12 consecutive patients in a single institution. Most patients presented with systemic symptoms and lymphadenopathy (92%), splenomegaly (100%) and hepatomegaly (67%). Neurologic symptoms were present in three patients, while involvement of other organs was present in five patients. The incidence of severe thrombocytopenia was 92% of anaemia 92% and of leucocytopenia 67%. Serum angiotensin converting enzyme, alpha 1-antitrypsin and lysozyme were independently increased in 6/9, 3/10 and 1/9 patients respectively. High serum levels of tumour necrosis factor (TNF) were present in 3/10 patients, while serum levels of interleukin-1 were normal in 10/10 patients. Histologic evidence of MH was obtained in all patients by repeated biopsies of involved tissues. Four patients died prior to treatment. Seven patients were treated with combination chemotherapy, consisting of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or MOPP (chloromethine, vincristine, procarbazine, prednisone), in some cases followed by non-cross-resistant second line chemotherapy, if no complete response was attained. The response rate of treated patients was 57%, and progression was observed in two patients. The median duration of response was 38 months. Three patients are alive without evidence of disease and off therapy (30+, 83+, 85+ months). Although MH is a potentially lethal disease, combination chemotherapy may offer a chance for cure in some patients. PMID- 2207003 TI - Haemophilia protects against ischaemic heart disease: a study of risk factors. AB - We previously reported that mortality due to ischaemic heart disease was lower in haemophilia patients than in the general male population. To support the hypothesis that this could be attributed to a protective effect of the clotting defect in haemophilia and not to differences in cardiovascular risk factors, we performed a second study. We examined 95 haemophilia patients for the presence of major risk factors for ischaemic heart disease and compared their risk factor profile with the data of epidemiologic surveys of the general Dutch population. Haemophilia patients had on average higher blood pressures than the comparison population, were more often hypertensive and used antihypertensive drugs twice as often. The mean serum cholesterol level of the patients was markedly lower than in the comparison population (4.8 versus 5.6 mmol/l, 95% confidence interval of the difference: 0.5-1.1 mmol/l). The risk factors were weighted into one theoretical risk ratio for ischaemic heart disease by application of logistic regression coefficients. The theoretical risk ratio based on the risk factor profile was 0.78. This risk ratio can only explain a moderate reduction in the incidence of ischaemic heart disease, much smaller than the mortality ratio of 0.20 we reported previously. Therefore these data support the hypothesis of a direct protective effect of haemophilia on the development of ischaemic heart disease. PMID- 2207005 TI - The platelet and plasma pools of plasminogen activator inhibitor (PAI-1) vary independently in disease. AB - The relative importance and behaviour of plasma and platelet plasminogen activator inhibitor (PAI-1) in disease has not hitherto been examined. In this study the concentration of PAI-1 in the plasma and platelets of patients with a variety of disorders was examined using a specific ELISA and a functional assay. Mean plasma PAI-1 was elevated in groups of patients with diabetes mellitus, hypertension, alcoholic cirrhosis, angina and myocardial infarction. Plasma PAI-1 was raised in the post-operative phase and the PAI-1 released after surgery was not derived from platelets. In all groups PAI-1 in the platelet pool reflected the platelet count, except in type II diabetes mellitus and chronic renal failure, where a reduced quantity of PAI-1 antigen per platelet was found. In severe chronic renal failure, abnormal platelets and diminished platelet PAI-1 may contribute to the haemorrhagic tendency sometimes seen in this disorder. Plasma PAI-1 represents a larger proportion of total circulating PAI-1 in disease than it does in healthy individuals; PAI-1 per platelet is abnormal only in a minority of disorders. Plasma and platelet pools of PAI-1 vary independently in disease and both merit consideration in evaluating the importance, if any, of PAI 1 in thrombosis or haemorrhage. PMID- 2207004 TI - Susceptibility to HIV infection and AIDS in Italian haemophiliacs is HLA associated. AB - We compared the frequencies of HLA antigens in two matched groups of 31 HIV seronegative and 31 HIV-seropositive haemophiliacs, exposed during the years 1981 85 to comparable amounts and batches of presumably infectious clotting factor concentrates. The frequency of A2 was significantly higher in HIV-seropositive than in seronegative haemophiliacs, with a relative risk (RR) of seroconversion of 3.92, whereas both Bw52 and DR4 were negatively associated with it. We also studied the distribution of HLA antigens in a larger group of 76 HIV-seropositive haemophiliacs, who were at different clinical stages of HIV infection (CDC classes II-IV) but were comparable for age and time elapsed since seroconversion. DR3 and DQw2 antigens were, particularly when concomitantly present, associated with a high risk of developing symptomatic HIV infection (RR = 11.79 and 25.33). Our data suggest that the HLA region controls susceptibility to infection with HIV and its progression to symptomatic disease in Italian haemophiliacs. PMID- 2207006 TI - The role of fibronectin in platelet aggregation. AB - A monoclonal antibody (anti-Fn2) was prepared which was reactive with both plasma fibronectin and fibronectin located within the platelet alpha granule. Immunoblotting analysis, on thermolysin digestion fragments of fibronectin, identified two immunoreactive fragments of Mr 145 kDa and 155 kDa which are known to contain a cell and DNA binding region. Anti-Fn2 was found to inhibit binding of fibronectin to platelets and DNA. Functional platelet studies, measuring platelet aggregation and 14C-serotonin release in washed platelet systems, demonstrated the ability of anti-Fn2 to totally inhibit low dose thrombin and low dose collagen induced platelet aggregation and serotonin release. Anti-Fn2 partially inhibited platelet aggregation induced by ADP (10 microM) and arachidonic acid, but had no effect on platelet aggregation induced by high-dose thrombin or by the calcium ionophore A23187. These studies indicate that fibronectin participates in platelet aggregation and release induced by a range of agonists and suggest that it has a more important involvement in platelet function than previously described. PMID- 2207007 TI - The platelet glycoprotein Ia-IIa-associated Br-alloantigen system is expressed by cultured endothelial cells. AB - To obtain information on the immunological relationship between the endothelial and platelet glycoprotein (GP)Ia-IIa (VLA-2) complex, we studied whether endothelial GPIa-IIa was able to express the platelet GPIa-IIa-associated Br alloantigen system. Therefore, we tested antisera to both allelic forms of the Br system (Bra and Brb) on platelets (by an assay based on monoclonal antibody specific immobilization of platelet antigens, MAIPA) and on cultured umbilical vein endothelial cells (by immunoprecipitation experiments) from the same individual. Endothelial cells from a platelet Br(a + b +), and from a platelet Br(a - b +) individual were studied. Our results indicate that endothelial GPIa IIa is indistinguishable from platelet GPIa-IIa in its ability to express the Bra and Brb alloantigens. The association of Br alloantigens with endothelial GPIa IIa was confirmed by the results of an assay based on monoclonal antibody specific immobilization of endothelial antigens (MAIEA). These data further illustrate the structural and immunologic similarity of platelet and endothelial cell GPIa-IIa (VLA-2). PMID- 2207008 TI - Isolation and characterization of the translation product of a beta-globin gene nonsense mutation (beta 121 GAA----TAA). AB - The beta o-thalassaemia gene of an individual who was a mixed heterozygote for this allele (GAA to TAA in codon 121) and beta(+)-thalassaemia (IVS-1 position 110 G to A) was examined to determine if the beta o-thalassaemia allele directed the synthesis of any detectable protein product. This beta o-thalassaemia allele was of particular interest, because it is the only example of a premature chain termination codon in the third exon of the beta-globin gene that produces thalassaemia. A very small amount of an abnormal protein was found in the red blood cells of the proband and was purified by preparative column chromatography. This abnormal protein was digested with trypsin, the peptides were separated by reverse phase high performance liquid chromatography (HPLC), and the amino acid content of each peptide was determined. All of the soluble beta-globin peptides were found except for T-13, T-14 and T-15 (residues 121-146), indicating the presence of a truncated protein that corresponded to the translation product of the beta 121 Glu----Term mRNA. This truncated globin was estimated to comprise between 0.05% and 0.1% of the total non-alpha-globin protein. These results may explain the phenotype of inclusion body beta-thalassaemia in heterozygotes, which is atypical of heterozygous beta o-thalassaemia. PMID- 2207009 TI - Blood transfusion in the para-Bombay phenotype. AB - The H-deficient phenotypes found in Chinese so far, have all been secretors of soluble blood group substances in saliva. The corresponding isoagglutinin activity (e.g. anti-B in OB(Hm) persons) has been found to be weak in all cases. To determine the clinical significance of these weak isoagglutinins 51Cr red cell survival tests were performed on three OB(Hm) individuals transfused with small volumes (4 ml) of groups B and O RBC. Rapid destruction of most of the RBC occurred whether or not the isoagglutinins of the OB(Hm) individuals were indirect antiglobulin test (IAGT) reactive. When a larger volume (54 ml packed RBC) of group B cells (weakly incompatible by IAGT) was transfused to another OB(Hm) individual with IAGT active anti-HI, the survival of the transfused RBC was 93% at 24 h, with 30% of the RBC remaining in the circulation at 28 d in contrast to 76% as would be expected if the survival was normal. Therefore when whole units of blood of normal ABO blood groups, compatible by IAGT, are transfused, the survival is expected to be almost normal. These weak isoagglutinins may not be very clinically significant and we suggest that when para-Bombay blood is not available, the compatibility testing for OA(Hm) persons should be performed with group A and group O packed RBC; OB(Hm) with group B and group O packed RBC: OAB(Hm) with groups A, B, AB and O packed RBC. For cross matching, the indirect antiglobulin test by a prewarmed technique should be used. PMID- 2207010 TI - Antilymphocyte globulin therapy enhances impaired function of natural killer cells and lymphokine activated killer cells in aplastic anaemia. AB - MHC-unrestricted cytotoxic lymphocytes, namely natural killer (NK) and lymphokine activated killer (LAK) cells, have been implicated in the regulation of haemopoiesis. To investigate the possible role of these lymphocytes in the pathogenesis of aplastic anaemia (AA), we studied their functions in the peripheral blood mononuclear cells (PBMC) and bone marrow mononuclear cells (BMMC) of patients with AA treated with antilymphocyte globulin (ALG). Before treatment, both NK and LAK activities in the PBMC of 25 patients were low (NK = 1.9 +/- 2.1 x 10(3) LU/l) LAK = 4.7 +/- 3.6 x 10(3) LU/l) compared to normal (NK = 6.0 +/- 3.0 x 10(3) LU/l, LAK = 10.0 +/- 3.5 x 10(3) LU/l) or multiply transfused (NK = 7.8 +/- 6.6 x 10(3) LU/l, LAK = 25.2 +/- 13.6 x 10(3) LU/l) controls. The NK and LAK activities in the BMMC in AA patients were not significantly different from those in PBMC. In all patients with low LAK and NK activities pre ALG there was an increase in activity 2-24 weeks after therapy which eventually reached normal levels and which was maintained for up to 2 years. Analysis of lymphocyte phenotypes in AA patients before treatment showed both significantly low mean proportion and absolute numbers of CD16+ cells compared to normals, which increased after therapy. Changes in MHC-unrestricted cytotoxicity and lymphocyte phenotypes post therapy were not correlated with haemopoietic recovery. These data suggest that ALG treatment can enhance the functions of MHC-unrestricted lymphocytes independently from haemopoiesis. It is unlikely that these cells play a role in the pathogenesis of AA. PMID- 2207012 TI - Revised recommendations for the measurements of the serum iron in human blood. Iron Panel of the International Committee for Standardization in Haematology. AB - Certain modifications to the previously published ICSH recommendations (1978) have been approved by the Iron Panel of the International Committee for Standardization in Haematology (ICSH). They include substitution of the chromogen bathophenanthroline sulphonate with ferrozine or ferene, which are more sensitive and cheaper, and a reduction in the volume of the test sample from 2 ml to 0.5 ml. PMID- 2207011 TI - Serum transferrin receptor as an index of iron absorption. AB - Recent studies indicate that serum transferrin receptor levels are a quantitative index of tissue receptor mass. To determine whether the latter plays a role in the regulation of iron absorption, we examined the relationship between serum receptor, serum ferritin and iron absorption in healthy subjects. Using radioisotopic techniques we measured absorption of inorganic iron in 174 subjects and dietary nonhaem iron in 60 subjects. With both forms of iron, the correlation with absorption was far lower for serum receptor than for serum ferritin and was no longer significant when subjects with depleted iron stores were excluded. These results indicate that in normal subjects the iron store is the main physiological determinant of iron absorption and that in the absence of iron deficiency, tissue receptor mass, reflected by serum transferrin receptor levels, has no discernible influence. PMID- 2207013 TI - Hematin therapy in late onset congenital erythropoietic porphyria. PMID- 2207014 TI - The successful treatment of a case of very severe aplastic anaemia with granulocyte-macrophage colony stimulating factor and anti-lymphocyte globulin. PMID- 2207015 TI - Alfa-interferon in a case of hypereosinophilic syndrome. PMID- 2207016 TI - A novel variant translocation t(2;13) (p23;q34) in Ki-1 large cell anaplastic lymphoma. PMID- 2207017 TI - Ten-year follow-up of HIV infection in a haemophiliac cohort. PMID- 2207018 TI - Ascorbate for the treatment of idiopathic thrombocytopenic purpura. PMID- 2207019 TI - Systemic vasculitis and myelodysplasia. PMID- 2207020 TI - Fibrosis in Hodgkin's disease. PMID- 2207021 TI - Cytogenetic and molecular analysis of relapse following bone marrow transplantation. PMID- 2207022 TI - [Eruption times of deciduous teeth]. PMID- 2207023 TI - Epilepsy information nights for parents. PMID- 2207025 TI - Working towards spinal cord injury prevention in adolescents. PMID- 2207024 TI - Codman Award paper--the experience of intensive care unit nurses providing care to the brain dead patient. AB - The brain dead patient is a by-product of advances in biomedical technology and the findings of this study confirm the view in the literature that caring for the brain dead patient is an emotionally laden process. This personal distress is directly related to two sources of inconsistencies. First, the nurse may possess coexisting beliefs, perceptions, values, opinions, knowledge and actions which are discrepant. Second, the nurse's personal values, knowledge, and behaviours may be in direct opposition to those of her nursing and medical colleagues and those of the family. The presence of the subjective tension results in the use of distancing tactics and/or the designation of a third person as the target of nursing care in an effort to reduce the personal and interpersonal dissonance. PMID- 2207026 TI - Pages from nursing's survival manual. Mary Glover lecture, June 1990. PMID- 2207027 TI - The hand-arm vibration syndrome: an update. PMID- 2207029 TI - Special nerve functions and colour discrimination in workers with long term low level exposure to carbon disulphide. AB - Certain functions of the peripheral and autonomic nervous systems, and colour discrimination were examined in 45 workers (mean age 49; mean exposure to carbon disulphide (CS2) 20 years) and 37 controls (mean age 48). Conduction velocity and refractory period of the peroneal and sural nerves were determined. The conduction velocity of the slower fibres of the peroneal nerve was measured by means of an improved method that makes use of the refractory period. Function of autonomic nerves was assessed by measuring the variation in heart rate during rest, during deep breathing, and during isometric muscle contraction. Colour discrimination was evaluated by the Lanthony desaturated test. Individual cumulative exposure to CS2 was calculated on the basis of exposure in the past and individual job history. Mean cumulative exposure was 165 ppm-years. The peroneal nerves of exposed workers showed a decrease (-1.0 m/s) in conduction velocity of the slow fibres and a prolongation (0.1 ms) of the refractory period (mean 1.6 ms) compared with controls. These effects were related to cumulative exposure. No impairment of function of the sural nerve or of colour discrimination was found. The muscle heart reflex was decreased in the exposed group, but this was not related to cumulative exposure. This study has established more firmly that a decrease in conduction velocity of slow motor fibres occurs at low levels of exposure to CS2. Extrapolation of the results suggests that small effects may occur after 40 years of exposure to concentrations below the present threshold limit value (10 ppm). PMID- 2207028 TI - Occupational exposure and defects of the central nervous system in offspring: review. AB - A study of published work was carried out in a search for evidence of a causal role for parental occupational exposure in the origin of structural and functional defects of the central nervous system (CNS) in children. Studies that consider this topic are scarce and mostly refer to broad categories of exposures and effects. Non-occupational studies referring to environmental exposure of humans and studies on experimental animals were also reviewed. The studies on animals provided straightforward evidence about morphological and behavioural abnormalities resulting from some agents used occupationally. The studies on humans yielded a scala of defects that could be ascribed to exposure to high doses of various agents in the environment. Evidence for a causal role of occupational exposure has not been found, but a highly probable influence on the developing CNS is hypothesised for lead, methyl mercury, and ionising radiation. Parental occupational exposure to cadmium, organic solvents, anaesthetics, and pesticides may also play a part in causing defects of the CNS. Well designed future research is needed to test the above hypotheses. PMID- 2207030 TI - Effects of methyl isocyanate on rat brain cells in culture. AB - Since the disaster in Bhopal, India, people exposed to methyl isocyanate (MIC) have complained of various disorders including neuromuscular dysfunction. In an attempt to get information about such dysfunction we have previously shown that MIC can affect muscle cells in culture. The present communication reports investigations into the effect of MIC on brain cells in culture. MIC was toxic to brain cells and the response was dose related. The observations were supported by light and electron microscopy. PMID- 2207032 TI - Abnormal pulmonary function associated with diaphragmatic pleural plaques due to exposure to asbestos. AB - Pulmonary function was measured in 79 men with diaphragmatic pleural plaques (DPP) as the only abnormality characteristic of asbestos disease on chest radiographs. They were selected from 4572 construction and shipyard workers exposed to asbestos. Abnormalities of pulmonary function in 21 non-smokers and 43 current smokers were compared with referent values adjusted for height, age, and duration of cigarette smoking. In the non-smokers, flows (FEV1) FEF75-85 and FEV1/FVC) were reduced and TGV and RV/TGV were raised. Current smokers had similar significant reductions. Thus by contrast with some current opinion that plaques are "an index only of past asbestos exposure," workers with plaques, even limited to the diaphragm, have functional impairment typical of pulmonary asbestosis. This suggests that they have pulmonary asbestosis, which is below the threshold of radiographic recognition. PMID- 2207031 TI - Mortality and cancer morbidity in cohorts of asbestos cement workers and referents. AB - Total and cause specific mortality and cancer morbidity were studied among 1929 asbestos cement workers with an estimated median cumulative exposure of 2.3 fibre (f)-years/ml (median intensity 1.2 f/ml, predominantly chrysotile). A local reference cohort of 1233 industrial workers and non-case referents from the exposed cohort were used for comparisons. The risk for pleural mesothelioma was significantly increased (13 cases out of 592 deaths in workers with at least 20 years latency). No case of peritoneal mesothelioma was found. A significant dose response relation was found for cumulative exposure 40 years or more before the diagnosis, with a multiplicative relative risk (RR) of 1.9 for each f-year/ml. No relation was found with duration of exposure when latency was accounted for. There was a significant overrisk in non-malignant respiratory disease (RR = 2.6). The overall risks for respiratory cancer, excluding mesothelioma, and for gastrointestinal cancer were not significantly increased. Surprisingly, colorectal cancer displayed a clear relation with cumulative dose, with an estimated increase of 1.6% in the incidence density ratio for each f-year/ml (but not with duration of exposure). PMID- 2207033 TI - Comparison of fibre types and size distributions in lung tissues of paraoccupational and occupational cases of malignant mesothelioma. AB - The results of analysis of mineral fibres in lung tissues from 10 paraoccupational cases of malignant mesothelioma were compared with analysis obtained from seven cases of malignant mesotheliomas that had developed in gas mask workers. Nine of the paraoccupational cases were considered to have developed their tumours because of exposure to asbestos on their husbands' working clothes and one cancer developed in the daughter of a man who had died of asbestosis. The gas mask workers had direct exposure to asbestos while working in a factory that produced military gas masks. The results of mineral fibre analysis in the paraoccupational cases were variable; six showed high crocidolite concentrations, seven raised amosite concentrations and two normal concentrations of all types of asbestos fibre measured. Chrysotile was raised in one case but crocidolite and amosite were also increased. The gas mask workers showed a consistent pattern with high crocidolite concentrations and normal or low concentrations of chrysotile and amosite. Fibre lengths for chrysotile were similar in both groups and predominantly less than 5 microns. Crocidolite fibres tended to be longer in the gas mask workers than in the paraoccupational group and longer than chrysotile in both groups. Amosite fibres tended to be more variable in width than those of chrysotile or crocidolite. PMID- 2207034 TI - Respiratory symptoms and lung function in hemp workers. AB - Respiratory symptoms and abnormalities of lung function were studied in 84 female and 27 male hemp workers employed in two textile mills (A and B) processing soft hemp (C sativa). In mill A 46 women and 27 men were investigated and 38 female workers were studied in mill B. Forty nine women and 30 men from a non-dusty industry served as controls. A significantly higher prevalence of almost all chronic respiratory symptoms was found in female hemp workers when compared to control workers. Among the men these differences were significant for nasal catarrh and sinusitis. A high prevalence of byssinosis was found among female hemp workers in both mills (group A, 47.8%; group B, 57.9%) as well as in the male workers (66.7%). Statistically significant across shift reductions in lung function were found for all ventilatory capacity measurements in female and male hemp workers varying from 7.1% for forced expiratory volume in one second (FEV1) to 15.1% for flow rates at 50% vital capacity (FEF50). Measured Monday baseline values before the work shift were significantly lower than expected for hemp workers, being particularly reduced for FEF25 and FEF50. The data suggest that occupational exposure to hemp dust is a significant risk factor for the development of acute and chronic lung disease in workers employed in this textile industry. PMID- 2207035 TI - Mortality from brain cancer and leukaemia among electrical workers. AB - The relation of brain cancer and mortality from leukaemia to electrical occupations was investigated in a case-control study based on all deaths in 1985 and 1986 in the 16 states in the United States that report occupational data from death certificates to the national vital statistics registry. The case series comprised all 2173 men who died of primary brain cancer (International Classification of Diseases-9 ((ICD-9) code 191) and all 3400 who died of leukaemia (ICD-9 codes 204-208). Each was matched with 10 controls who died of other causes in the same year. Men employed in any electrical occupation had age race adjusted odds ratios (ORs) of 1.4 (95% confidence interval (CI) 1.1-1.7) for brain cancer and 1.0 (95% CI 0.8-1.2) for leukaemia, compared with men in all other occupations. Brain cancer odds ratios were larger for electrical engineers and technicians (OR 2.7, 95% CI 2.1-3.4), telephone workers (OR 1.6, 95% CI 1.1 2.4), electric power workers (OR 1.7, 95% CI 1.1-2.7), and electrical workers in manufacturing industries (OR 2.1, 95% CI 1.3-3.4). There was some evidence of excess leukaemia among the same groups (ORs of 1.1-1.5) despite absence of an association for all electrical workers. The excess of deaths from brain cancer was concentrated among men aged 65 or older, whereas leukaemia was associated with electrical work only among younger decedents and those with acute lymphocytic leukaemia. These results from a large and geographically diverse population corroborate reports of increased mortality from brain cancer among electrical workers, but gives only limited support to suggestions of excess deaths from leukaemia. PMID- 2207037 TI - Evaluation of a system recording non-pneumoconiotic abnormalities as part of coal worker's x-ray surveillance programme. PMID- 2207036 TI - Role of manmade mineral fibres in the causation of cancer. PMID- 2207038 TI - Horizontal-T genioplasty--(a modified technique for the broad or asymmetrical chin). AB - A modified technique for genioplasty is described. A horizontal, single-slice of bone is sectioned from the inferior border of the chin, with preservation of the lingual soft tissue attachment, in the conventional manner. This is divided sagittally into three segments, which are not necessarily equal, and are then repositioned in the shape of a horizontal 'T'. To achieve this, the lateral segments are advanced and approximated in front of the central fragment which itself is also advanced. These are fixed in position and when desirable any voids may be filled with autogenous bone or hydroxyapatite. This simple technique augments the chin to an equal if not to a greater extent than the conventional 'double slide' genioplasty. It combines augmentation with narrowing and has the flexibility to reposition the chin. This technique is not advocated for routine use but more for the special case when augmentation is required for the patient with a broad, flat or asymmetrical chin. A presentation of four case histories will illustrate the application of this technique. PMID- 2207039 TI - Treatment of large oro-nasal fistulae using a triple-layer technique: 38 cases. AB - A one stage, triple-layer technique for the closure of large oro-nasal defects is described. This technique has been used successfully in 37 out of 38 cases. PMID- 2207041 TI - Parotid gland biopsy for investigation of xerostomia. AB - A technique is described for biopsy of the parotid salivary gland under local anaesthesia, which has been undertaken for a series of 59 patients who presented with suspected inflammatory exocrinopathy. The procedure is reliable and is associated with negligible postoperative discomfort. The advantages of the technique suggest that parotid gland biopsy is an acceptable alternative to conventional lower lip biopsy of minor salivary glands in the investigation of xerostomia. PMID- 2207040 TI - Arthrotomography and the surgical correction of temporomandibular joint disorders. AB - Over a 2-year-period, 321 new patients were seen at one clinic with temporomandibular joint dysfunction and pain. Sixty-seven (21%) of these who did not respond to 12 weeks medical therapy, had arthrotomography performed and 24 patients (7.5%) underwent surgery to the joint. Eighteen (75%) of these patients were free of pain 1 year later, although this success was not always sustained without medical therapy. Meniscus adhesions were under-estimated on arthrotomography compared to surgical findings and meniscus perforations were over diagnosed. However, increased accuracy in preoperative diagnosis was seen with experience. There was only one false positive result which lead to unnecessary surgery. PMID- 2207042 TI - A method of assessment in cases of lingual nerve injury. AB - A method for assessing lingual sensation is described, comprising sensory testing, using touch and moving two-point discrimination and patient subjective reporting. The clinical application is seen to be the evaluation of lingual nerve injury consequent upon lower third molar surgery. Using this method it is considered possible to identify many of those patients unlikely to make full spontaneous recovery at the stage of 3 months following injury, with a view to achieving an earlier timing of surgical repair than that which prevails at present. PMID- 2207043 TI - The attachments of the temporomandibular joint meniscus in the human fetus. AB - The temporomandibular joints of human fetuses aged between 13 and 21 weeks have been examined by gross dissection and serial sections. An uninterrupted continuation of fibres has been observed from the superior head of the lateral pterygoid muscle to the malleus. PMID- 2207044 TI - A clinical and biomechanical assessment of the Hall surgical miniplate system. AB - The Hall surgical miniplating system has been evaluated for use in maxillofacial trauma and orthognathic surgery. The biomechanical characteristics of the plates have been examined and experience gained, using 53 plates, in 25 patients is presented. The feature which distinguishes these plates is the narrow bridge between paired screw platforms. The specially designed screwdriver has a splined head which allows screw transfer to be carried out as a one-handed procedure. The plates show considerable advantages over existing small plate systems in their size, malleability and consequent ease of handling. PMID- 2207046 TI - Surgical ciliated (postoperative maxillary) cysts following mid-face osteotomies. AB - Surgical ciliated (postoperative maxillary) cysts have been reported extensively as occurring 6 months to 50 years after radical surgery for maxillary sinusitis. Three cases are presented in which these aggressive cysts occurred 3 to 4 years after Le Fort I, II and III mid-face osteotomies. The presentation, treatment and possible aetiology are discussed and some attempt made to clarify the descriptive terms used in the literature. PMID- 2207045 TI - An introduction to the 'Mennen plate' and its use in treatment of fractures of the edentulous mandible. AB - A paraskeletal clamp plate (Mennen) offers a novel method of fixation for mandibular fractures. Its application is relatively atraumatic and this together with the minimal disruption to the local blood supply may make this clamp particularly suited to fixation of fractures of the atrophic edentulous jaw. Its use in six such cases is reported. PMID- 2207047 TI - Botryoid odontogenic cyst: report of a case with clinical and histogenetic considerations. AB - A case of a botryoid odontogenic cyst is reported. Some considerations regarding histogenetic and biologic behaviour of the lesion are discussed. PMID- 2207048 TI - Prophylactic antibiotics. PMID- 2207050 TI - Occlusal indices revisited. AB - With the increased interest in measuring the need for orthodontic treatment and the quality of the outcome of orthodontic care, the difficulties in using Grainger's Treatment Priority Index (TPI) to screen children in their tenth year is considered. The first part of the study investigated the level of validity of the TPI using 137 study models and three orthodontists. In the light of the results obtained, the TPI was modified. The clinical judgement of a further two orthodontists was compared with the scores obtained form the modified TPI, using another 121 study models. Three Community Dental Officers were employed initially to assess the training needs for personnel who were not trained in orthodontics. A further five Community Dental Officers were involved in the final training programmes. It was concluded that it will be very difficult to produce an index which considers all aspects of malocclusion and which can be used consistently by personnel untrained in orthodontics. PMID- 2207049 TI - Regional variation in the provision of orthodontic treatment by the hospital services in England and Wales. AB - The regional variation in hospital orthodontic manpower, referral rate, and hospital treatment rate for the 5-15-year-old population was calculated, a marked regional variation was evident. In addition, relevant data from the Consultant Orthodontist Survey of 1985 was also analysed on a regional basis, in order to evaluate any interactions between the above variables and the type of treatment provided, the proportion of referred patients accepted, and treatment priority of patients referred. It was found that the hospital treatment rate was related to the referral rate, no other relevant significant correlations between the variables were detected. Possible explanations are discussed. PMID- 2207051 TI - Overjet relapse following functional appliance therapy. AB - This cephalometric study of individuals with Class II Division 1 malocclusion investigated changes occurring during and following treatment for 49 patients treated with either the Andresen activator or the Bionator (mean age initially 12.1 +/- 1.1 years). The treated cases were compared with an untreated group of 24 patients (mean age initially 11.8 +/- 0.5 years). Overjet reduction was found to occur mainly as a result of dento-alveolar change. Mean overjet relapse following treatment was small (0.8 mm), but individual variation was considerable (+5.2 to -3.7 mm). Changes in incisor inclination rather than antero-posterior skeletal change contributed to relapse. No evidence was found to suggest that vertical facial pattern or growth influenced relapse. Small, but significant correlations were found between the magnitude of overjet relapse and the reduction achieved during treatment (r = -0.42) and between the magnitude of upper incisor retroclination during treatment and proclination post-treatment (upper incisor to SN plane, r = -0.42). The only initial variable showing a significant correlation with overjet relapse was initial overjet and the value for this correlation was low (r = 0.31). PMID- 2207052 TI - A comparison of the gum pads of Afro-Caribbean and Caucasian British subjects at birth. AB - The gum pads of 34 subjects of Afro-Caribbean origin are compared with those of an equal number of Caucasian British subjects, matched for sex and birth weight. Some differences of size, form, and relationship are described, and are considered large enough to merit further investigation on a larger sample. PMID- 2207053 TI - Glass ionomers for direct bonding: an in vitro assessment. AB - An in vitro study was carried out testing the shear/peel bonding strength of brackets cemented with a glass-ionomer cement. It was found that the adhesive achieves its optimal bond strength at 24 hours. It is suggested that there is still scope for improvement of the material's mechanical properties and the use of prolonged clinical trials. PMID- 2207054 TI - Residual lower first premolar extraction space. AB - Residual lower first premolar extraction space was examined in 43 subjects, 16 male and 27 female, 5 years after extraction; 16 subjects were treated mechanically, 27 had no active treatment. Forty per cent of extraction sites had residual spaces averaging 0.62 mm left and 0.71 mm right. Various parameters were measured to try to establish reasons for non-closure of spaces. These included buccal space condition and incisal space condition measured on the pre-extraction models, and alveolar atrophy assessed on final models. The angulation of second premolars and canine to the maxillary plane and molar space were measured on 60 degrees cephalograms. Changes in these three parameters were measured after superimposing a tracing of the pre-extraction film on the final film. Angulation of lower incisors to the maxillary plane was measured on pre-extraction 90 degrees cephalograms, and change in lower incisor angulation and position measured after superimposing a tracing on the final 90 degrees film. PMID- 2207055 TI - Stability and relapse of dental arch alignment. AB - For more than 35 years, research in the Department of Orthodontics, University of Washington has focused on a growing collection of over 600 sets of patient records to assess stability and failure of orthodontic treatment. All had completed treatment a decade or more prior to the last set of data. Evaluation of treated premolar extraction cases, treated non-extraction cases with generalized spacing, cases treated by arch enlargement strategies, and untreated normal occlusions demonstrate similar physiological changes. 1. Arch length reduces following orthodontic treatment, but also does so in untreated normal occlusions. 2. Arch width measured across the mandibular canine teeth typically reduces post treatment whether the case was expanded during treatment or not. 3. Mandibular anterior crowding during the post-treatment phase is a continuing phenomenon well into the 20-40 age bracket and likely beyond. 4. Third molar absence or presence, impacted or fully erupted, seems to have little effect on the occurrence or degree of relapse. 5. The degree of post-retention anterior crowding is both unpredictable and variable and no pretreatment variables either from clinical findings, casts, or cephalometric radiographs before or after treatment seem to be useful predictors. PMID- 2207056 TI - Dental anomalies in cleft lip and palate: an unusual case. AB - A cleft palate case is reported in which there is an unusual pattern of hypodontia involving aplasia of the primary second molars, but development of the corresponding second premolars. This paper discusses some of the implications of this situation and stresses the need for very thorough clinical and radiographic examination. PMID- 2207057 TI - AUTO report. PMID- 2207058 TI - Natural head position/a discussion of concepts. PMID- 2207059 TI - Full-time academic posts in orthodontics. An Association of University Teachers of Orthodontics (AUTO) report. PMID- 2207060 TI - Joint report on specialist registration in orthodontics. PMID- 2207061 TI - A novel enzyme from bovine neurointermediate pituitary catalyzes dealkylation of alpha-hydroxyglycine derivatives, thereby functioning sequentially with peptidylglycine alpha-amidating monooxygenase in peptide amidation. AB - We report here the isolation of a novel enzyme from bovine neurointermediate pituitary which catalyzes the conversion of alpha-hydroxybenzoylglycine to benzamide. This enzyme, termed HGAD (alpha-hydroxyglycine amidating dealkylase), is a soluble protein with an apparent molecular mass of 45 kDa and no apparent cofactor requirement. Addition of HGAD to purified neurointermediate pituitary PAM (peptidylglycine alpha-amidating monooxygenase, EC 1.14.17.3) increases the rate of formation of amide products by an order of magnitude. Sequential additions of PAM and HGAD gave results consistent with PAM first catalyzing the formation of an intermediate that is subsequently, in a separate reaction, converted by HGAD to the final amide product. Experiments with olefinic inactivators demonstrate that HGAD is not required for turnover-dependent inactivation of PAM and, correspondingly, that HGAD activity is not affected by inactivators of PAM. As expected, HGAD has no effect on the rate of PAM-catalyzed sulfoxidation, where a reaction analogous to that occurring during amidation of glycine-extended substrates is not possible. On the basis of these results, we propose that peptide C-terminal amidation in neurointermediate pituitary is a two step process, with PAM first catalyzing the conversion of a glycine-extended peptide to the alpha-hydroxyglycine derivative, which is in turn converted to the final amide product by HGAD. PMID- 2207062 TI - Domain structure in yeast tRNA ligase. AB - Yeast tRNA ligase is one of two proteins required for the splicing of precursor tRNA molecules containing introns. The 95-kDa tRNA ligase has been purified to homogeneity from a strain of Escherichia coli which overexpresses the protein. The ligation reaction requires three enzymatic activities: phosphodiesterase, polynucleotide kinase, and ligase. By partial proteolytic digestion, we have produced fragments of tRNA ligase which contain the constituent activities. These results provide evidence for a model in which the three constituent activities of ligase are located in three distinct domains separated by protease-sensitive regions. We have also located the active adenylylated site in the ligase domains. It is lysine-114. The tRNA ligase sequence in this region has limited homology to the active-site region of T4 RNA ligase. PMID- 2207063 TI - Preferential binding of daunomycin to 5'ATCG and 5'ATGC sequences revealed by footprinting titration experiments. AB - Results from a high-resolution deoxyribonuclease I (DNase I) footprinting titration procedure are described that identify preferred daunomycin binding sites within the 160 bp tyr T DNA fragment. We have obtained single-bond resolution at 65 of the 160 potential binding sites within the tyr T fragment and have examined the effect of 0-3.0 microM total daunomycin concentration on the susceptibility of these sites toward digestion by DNase I. Four types of behavior are observed: (i) protection from DNase I cleavage; (ii) protection, but only after reaching a critical total daunomycin concentration; (iii) enhanced cleavage; (iv) no effect of added drug. Ten sites were identified as the most strongly protected on the basis of the magnitude of the reduction of their digestion product band areas in the presence of daunomycin. These were identified as the preferred daunomycin binding sites. Seven of these 10 sites are found at the end of the triplet sequences 5'ATGC and 5'ATCG, where the notation AT indicates that either A or T may occupy the position. The remaining three strongly protected sites are found at the ends of the triplet sequence 5'ATCAT. Of the preferred daunomycin binding sites we identify in this study, the sequence 5'ATCG is consistent with the specificity predicted by the theoretical studies of Chen et al. [Chen, K.-X., Gresh, N., & Pullman, B. (1985) J. Biomol. Struct. Dyn. 3, 445-466] and is the very sequence to which daunomycin is observed to be bound in two recent X-ray crystallographic studies. Solution studies, theoretical studies, and crystallographic studies have thus converged to provide a consistent and coherent picture of the sequence preference of this important anticancer antibiotic. PMID- 2207064 TI - Mutagenesis by site-specific arylamine adducts in plasmid DNA: enhancing replication of the adducted strand alters mutation frequency. AB - Site specifically modified plasmids were used to determine the mutagenic effects of single arylamine adducts in bacterial cells. A synthetic heptadecamer bearing a single N-(guanin-8-yl)-2-aminofluorene (AF) or N-(guanin-8-yl)-2 (acetylamino)fluorene (AAF) adduct was used to introduce the adducts into a specific site in plasmid DNA that contained a 17-base single-stranded region complementary to the modified oligonucleotide. Following transformation of bacterial cells with the adduct-bearing DNA, putative mutants were detected by colony hybridization techniques that allowed unbiased detection of all mutations at or near the site of the adduct. The site-specific AF or AAF adducts were also placed into plasmid DNA that contained uracil residues on the strand opposite that bearing the lesions. The presence of uracil in one strand of the DNA decreases the ability of the bacterial replication system to use the uracil containing strand, thereby favoring the use of the strand bearing the adducts. In a comparison of the results obtained with site specifically modified DNA, either with or without uracil, the presence of the uracil increased the mutation frequencies of the AF adduct by greater than 7-fold to 2.9% and of the AAF adduct by greater than 12-fold to 0.75%. The mutation frequency of the AF adduct was greatly reduced in a uvrA- strain while no mutations occurred with the AAF adduct in this strain. The sequence changes resulting from these treatments were dependent on adduct structure and the presence or absence of uracil on the strand opposite the adducts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2207065 TI - Physical studies of DNA premelting equilibria in duplexes with and without homo dA.dT tracts: correlations with DNA bending. AB - We have employed a variety of physical methods to study the equilibrium melting and temperature-dependent conformational dynamics of dA.dT tracts in fractionated synthetic DNA polymers and in well-defined fragments of kinetoplast DNA (kDNA). Using circular dichroism (CD), we have detected a temperature-dependent, "premelting" event in poly(dA).poly(dT) which exhibits a midpoint near 37 degrees C. Significantly, we also detect this CD "premelting" behavior in a fragment of kDNA. By contrast, we do not observe this "premelting" behavior in the temperature-dependent CD spectra of poly[d(AT)].poly[d(AT)], poly(dG).poly(dC), poly[d(GC)].poly[d(GC)], or calf thymus DNA. Thus, poly(dA).poly(dT) and kDNA exhibit a common CD-detected "premelting" event which is absent in the other duplex systems studied in this work. Furthermore, we find that the anomalous electrophoretic retardation of the kDNA fragments we have investigated disappears at temperatures above approximately 37 degrees C. We also observe that the rotational dynamics of poly(dA).poly(dT) and kDNA as assessed by singlet depletion anisotropy decay (SDAD) and electric birefringence decay (EBD) also display a discontinuity near 37 degrees C, which is not observed for the other duplex systems studied. Thus, in the aggregate, our static and dynamic measurements suggest that the homo dA.dT sequence element [common to both poly(dA).poly(dT) and kDNA] is capable of a temperature-dependent equilibrium between at least two helical states in a temperature range well below that required to induce global melting of the host duplex. We suggest that this "preglobal" melting event may correspond to the thermally induced "disruption" of "bent" DNA. PMID- 2207066 TI - Light-dependent degradation of the D1 protein in photosystem II is accelerated after inhibition of the water splitting reaction. AB - Strong illumination of oxygen-evolving organisms inhibits the electron transport through photosystem II (photoinhibition). In addition the illumination leads to a rapid turnover of the D1 protein in the reaction center of photosystem II. In this study the light-dependent degradation of the D1 reaction center protein and the light-dependent inhibition of electron-transport reactions have been studied in thylakoid membranes in which the oxygen evolution has been reversibly inhibited by Cl- depletion. The results show that Cl(-)-depleted thylakoid membranes are very vulnerable to damage induced by illumination. Both the D1 protein and the inhibition of the oxygen evolution are 15-20 times more sensitive to illumination than in control thylakoid membranes. The presence, during the illumination, of the herbicide 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) prevented both the light-dependent degradation of the D1 protein and the inhibition of the electron transport. The protection exerted by DCMU is seen only in Cl(-)-depleted thylakoid membranes. These observations lead to the proposal that continuous illumination of Cl(-)-depleted thylakoid membranes generates anomalously long-lived, highly oxidizing radicals on the oxidizing side of photosystem II, which are responsible for the light-induced protein damage and inhibition. The presence of DCMU during the illumination prevents the formation of these radicals, which explains the protective effects of the herbicide. It is also observed that in Cl(-)-depleted thylakoid membranes, oxygen evolution (measured after the readdition of Cl-) is inhibited before electron transfer from diphenylcarbazide to dichlorophenolindophenol.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2207067 TI - Mapping of a cholinergic binding site by means of synthetic peptides, monoclonal antibodies, and alpha-bungarotoxin. AB - Previous studies by several laboratories have identified a narrow sequence region of the nicotinic acetylcholine receptor (AChR) alpha subunit, flanking the cysteinyl residues at positions 192 and 193, as containing major elements of, if not all, the binding site for cholinergic ligands. In the present study, we used a panel of synthetic peptides as representative structural elements of the AChR to investigate whether additional segments of the AChR sequences are able to bind alpha-bungarotoxin (alpha-BTX) and several alpha-BTX-competitive monoclonal antibodies (mAbs). The mAbs used (WF6, WF5, and W2) were raised against native Torpedo AChR, specifically recognize the alpha subunit, and bind to AChR is inhibited by all cholinergic ligands. WF6 competes with agonists, but not with low mol. wt. antagonists, for AChR binding. The synthetic peptides used in this study were approximately 20 residue long, overlapped each other by 4-6 residues, and corresponded to the complete sequence of Torpedo AChR alpha subunit. Also, overlapping peptides, corresponding to the sequence segments of each Torpedo AChR subunit homologous to alpha 166-203, were synthesized. alpha-BTX bound to a peptide containing the sequence alpha 181-200 and also, albeit to a lesser extent, to a peptide containing the sequence alpha 55-74. WF6 bound to alpha 181 200 and to a lesser extent to alpha 55-74 and alpha 134-153. The two other mAbs predominantly bound to alpha 55-74, and to a lesser extent to alpha 181-200. Peptides alpha 181-200 and alpha 55-74 both inhibited binding of 125I-alpha-BTX to native Torpedo AChR. None of the peptides corresponding to sequence segments from other subunits bound alpha-BTX or WF6, or interfered with their binding. Therefore, the cholinergic binding site is not a single narrow sequence region, but rather two or more discontinuous sequence segments within the N-terminal extracellular region of the AChR alpha subunit, folded together in the native structure of the receptor, contribute to form a cholinergic binding region. Such a structural arrangement is similar to the "discontinuous epitopes" observed by X ray diffraction studies of antibody-antigen complexes [reviewed in Davies et al. (1988)]. PMID- 2207068 TI - An integumentary mucin (FIM-B.1) from Xenopus laevis homologous with von Willebrand factor. AB - We present a new protein from X. laevis skin termed "frog integumentary mucin B.1" (FIM-B.1) with a general structure similar to FIM-A.1 (formerly "spasmolysin"). The central region consisting of tandem repeats of 11 amino acid residues is probably a target for extensive O-glycosylation, whereas the C terminal cysteine-rich domain shows pronounced homology with the C1-C2 domains and the C-terminal end of von Willebrand factor. Furthermore, we describe homology with antistasin, an anticoagulant peptide from a leech. We also discuss some implications concerning the evolutionary origin of von Willebrand factor. In situ hybridization studies revealed the expression of FIM-B.1 exclusively in mucous glands of the skin. This is comparable with FIM-A.1 but is in contrast to all other physiologically active peptides, which are synthesized in granular glands. PMID- 2207069 TI - Calcium binding in alpha-amylases: an X-ray diffraction study at 2.1-A resolution of two enzymes from Aspergillus. AB - X-ray diffraction analysis (at 2.1-A resolution) of an acid alpha-amylase from Aspergillus niger allowed a detailed description of the stereochemistry of the calcium-binding sites. The primary site (which is essential in maintaining proper folding around the active site) contains a tightly bound Ca2+ with an unusually high number of eight ligands (O delta 1 and O delta 2 of Asp175, O delta of Asn121, main-chain carbonyl oxygens of Glu162 and Glu210, and three water molecules). A secondary binding site was identified at the bottom of the substrate binding cleft; it involves the residues presumed to play a catalytic role (Asp206 and Glu230). This explains the inhibitory effect of calcium observed at higher concentrations. Neutral Aspergillus oryzae (TAKA) alpha-amylase was also refined in a new crystal at 2.1-A resolution. The structure of this homologous (over 80%) enzyme and additional kinetic studies support all the structural conclusions regarding both calcium-binding sites. PMID- 2207071 TI - Conformation of membrane fusion-active 20-residue peptides with or without lipid bilayers. Implication of alpha-helix formation for membrane fusion. AB - Fusion of small unilamellar vesicles of egg phosphatidylcholine can be triggered with synthetic 20-residue peptides. Taking the N-terminal amino acid sequence of HA-2 polypeptide of influenza virus as a guideline, we designed and synthesized several peptides having amphiphilic structures. Among the peptides so far studied, those active to induce membrane fusion took an alpha-helical conformation in the presence of phospholipid bilayers, while a peptide which was unable to induce membrane fusion was in a beta-structure. Mixing of a pair of positively and negatively charged peptides, which had a complementary arrangement of electric charges to each other, resulted in alpha-helix formation at neutral pH, the condition of forming a randomly coiled conformation for each peptide. We concluded that alpha-helix formation was one of the necessary conditions to trigger a process of membrane fusion, at least in the present set of peptides. Characteristic features of these amphiphilic peptides are also described. PMID- 2207070 TI - Effect of the carbohydrate moiety on the secondary structure of beta 2 glycoprotein. I. Implications for the biosynthesis and folding of glycoproteins. AB - By use of six highly purified exoglycosidases with well-defined specificity, the oligosaccharide units of human plasma beta 2-glycoprotein I (beta 2I) were modified by sequential enzymatic degradation. The released monosaccharides (NeuAc, Gal, GlcNAc, and Man) were quantified, and the carbohydrate compositions of the resulting glycoprotein (gp) derivatives were determined. The gp was found to be both partially sialylated and galactosylated. These findings which are in agreement with earlier reports suggest that the carbohydrate moiety of beta 2I possesses more bi- than tri-antennas, probably three of the former and two of the latter carbohydrate units. Circular dichroic (CD) spectra of native beta 2I and its derivatives were measured in aqueous buffer and 2-chloroethanol (2-CE). Analysis of these spectra for elements of secondary structure showed beta 2I and most of the derivatives to contain predominantly beta-sheet and beta-turn structures. The lack of alpha-helical structures in aqueous buffer was noted. Removal of a large portion of the carbohydrate moiety did not alter the CD spectra or secondary structure of beta 2I in either aqueous buffer or in 2-CE. However, after enzymatic removal of approximately 96% of the carbohydrate moiety, large significant changes in the spectra and secondary structures were observed. In aqueous buffer a shift in the wavelength minimum occurred, accompanied by an increase in the magnitude of the molar ellipticity and the amount of beta-turn, with a reduction in random coil. One-third of the amino acids which were originally in random coil conformation assumed beta-turns after removal of 96% of the carbohydrate moiety.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2207072 TI - Role of arginine 67 in the stabilization of chymotrypsin inhibitor 2: examination of amide proton exchange rates and denaturation thermodynamics of an engineered protein. AB - We have examined the contribution to protein stability of an interaction involving a charged hydrogen bond from an arginyl side chain (Arg67) in the serine proteinase inhibitor chymotrypsin inhibitor 2 (CI-2), by replacing this side chain with an alanyl residue by protein engineering. Using nuclear magnetic resonance spectroscopy (NMR), we have examined the effect of this mutation on the hydrogen-deuterium exchange rates of several backbone amide protons in the native and engineered proteins at 50 degrees C. These exchange rates provide a localized probe at multiple discrete sites throughout the protein and from comparison of native and mutant exchange rates allow calculation of the difference in free energy of exchange (delta delta Gex) resulting from the mutation. The results show that for the majority of amides observed this mutation results in delta delta Gex of ca. 1.7 kcal mol-1 over the whole CI-2 molecule. However, for two relatively exposed amide protons the exchange rates are found to be far less perturbed, implying that local unfolding mechanisms predominate for these protons. Direct measurement of the stability of both proteins to denaturation by guanidinum hydrochloride shows that the interaction contributes 1.4 kcal mol-1 to the stability of the molecule. This value is comparable to those obtained from the NMR exchange measurements and indicates that the exchange processes reflect the differences in stability between the native and mutant proteins.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2207073 TI - Nucleoside inhibitors of rhodopsin kinase. AB - The specificity of the ATP-binding site of rhodopsin kinase was studied with adenosine analogues that are competitive inhibitors. Systematic changes in the ribose ring (position 5') and the purine ring (positions 2, 6, 7, 8, and 9) and determination of the inhibitory properties of these analogues lead to the following conclusions: (1) The N6 nitrogen in the purine ring is essential for binding at the active site, which may explain the marked preference for ATP rather than GTP as substrate. (2) The configuration of the sugar moiety is critical for the binding. (3) Positions 2, 3, and 8 of the purine ring, as well as the polyphosphate chain, play a minor role in substrate recognition by rhodopsin kinase. (4) ATP gamma S is a good substrate for rhodopsin kinase (thus rhodopsin phosphorothioate, a phosphatase-resistant product, can be formed in order to study the role of phosphorylation in rod outer segments). Pyrrolopyrimidine derivatives are very potent inhibitors of rhodopsin kinase. The Ki of one of these, sangivamycin, is 180 nM. Sangivamycin in solution assumes the anti conformation, as determined by nuclear Overhauser measurement. These measurements show that the most potent inhibitors of rhodopsin kinase, sangivamycin and toyocamycin, occur in solution preferentially in the anti conformation. Many nucleotides and nucleosides tested that are not inhibitors are syn, and many that are inhibitors form a mixture of syn and anti. The hypothesis that inhibitors may have a conformation intermediate between syn and anti was strengthened by testing a cyclic nucleoside locked in an anti conformation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2207074 TI - Infrared spectra of carbonyl hemoglobins: characterization of dynamic heme pocket conformers. AB - The infrared spectra for carbon monoxide complexed to hemoglobins were examined in the C-O stretch region. Deconvolution of the spectra requires four bands and supports the presence of four distinct conformers at the ligand binding site. Most typical hemoglobins exhibit only one predominant conformer for each subunit represented by a band at 1951 cm-1 in contrast to myoglobins, which typically exist in two major conformations. Several hemoglobins with an enlarged heme pocket are shown to shift the C-O frequency into the higher frequency conformer regions. Many factors, including pH, temperature, solvents, and divalent metals, are also shown to be capable of expanding the heme pocket. Only very specific structural changes that can reduce the size of the heme pocket will result in the lower frequency conformers. The weighted averages of the multiple CO vibrational frequencies are linearly related to the single 13CO NMR chemical shift values and to the exponential of fast CO on-rates. Conformer interconversion occurs at a rate greater than 10(4) s-1. The infrared C-O stretch spectra provide qualitative and quantitative information on the structural dynamics, stability, and ligand binding properties of hemoglobins. PMID- 2207075 TI - Hydrogen exchange kinetics in a membrane protein determined by 15N NMR spectroscopy: use of the INEPT experiment to follow individual amides in detergent-solubilized M13 coat protein. AB - The coat protein of the filamentous coliphage M13 is a 50-residue polypeptide which spans the inner membrane of the Escherichia coli host upon infection. Amide hydrogen exchange kinetics have been used to probe the structure and dynamics of M13 coat protein which has been solubilized in sodium dodecyl sulfate (SDS) micelles. In a previous 1H nuclear magnetic resonance (NMR) study [O'Neil, J. D. J., & Sykes, B. D. (1988) Biochemistry 27, 2753-2762], multiple exponential analysis of the unresolved amide proton envelope revealed the existence of two slow "kinetic sets" containing a total of about 30 protons. The slower set (15-20 amides) originates from the hydrophobic membrane-spanning region and exchanges at least 10(5)-fold slower than the unstructured, non-H-bonded model polypeptide poly(DL-alanine). Herein we use 15N NMR spectroscopy of biosynthetically labeled coat protein to follow individual, assigned, slowly exchanging amides in or near the hydrophobic segment. The INEPT (insensitive nucleus enhancement by polarization transfer) experiment [Morris, G. A., & Freeman, R. (1979) J. Am. Chem. Soc. 101, 760-762] can be used to transfer magnetization to the 15N nucleus from a coupled proton; when 15N-labeled protonated protein is dissolved in 2H2O, the INEPT signal disappears with time as the amide protons are replaced by solvent deuterons. Amide hydrogen exchange is catalyzed by both H+ and OH- ions. Base catalysis is significantly more effective, resulting in a characteristic minimum rate in model peptides at pH approximately equal to 3. Rate versus pH profiles have been obtained by using the INEPT experiment for the amides of leucine-14, leucine-41, tyrosine-21, tyrosine-24, and valines-29, -30, -31, and 33 in M13 coat protein. The valine residues exchange most slowly and at very similar rates, showing an apparent 10(6)-fold retardation over poly(DL-alanine). A substantial basic shift in the pH of the minimum rate (up to 1.5 pH units) was also observed for some residues. Possible reasons for the shift include accumulation of catalytic H+ ions at the negatively charged micelle surface or destabilization of the negatively charged transition state of the base-catalyzed reaction by either charge or hydrophobic effects within the micelle. The time dependent exchange-out experiment is suitable for slow exchange rates (kex), i.e., less than (1-2) x 10(-4) s-1.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2207077 TI - Covalent modification reactions are marking steps in protein turnover. PMID- 2207076 TI - A ceramide analogue inhibits T cell proliferative response through inhibition of glycosphingolipid synthesis and enhancement of N,N-dimethylsphingosine synthesis. AB - The ceramide analogue 1-phenyl-2-(decanoylamino)-3-morpholino-1-propanol (PDMP) (particularly the D-threo isomer, D-PDMP) caused inhibition of cell growth in some types of cells, and this growth-inhibitory effect has been attributed to inhibition of UDP-Glc:Cer beta-Glc transferase, resulting in reduced glycolipid synthesis and increased free ceramide [Inokuch, J., & Radin, N. S. (1987) J. Lipid Res. 28, 565-571; Okada, Y., et al. (1988) FEBS Lett. 235, 25-29]. In view of increasing evidence that the T cell proliferative immune response is modulated by glycosphingolipids (GSLs), the reagent D-PDMP was used to evaluate the role of GSLs in this respect. Con A induced or PHA-induced mitogenesis of C3H/HeJ mouse splenocytes, as well as IL2-dependent CTLL cell growth, were strongly inhibited in a dose-dependent manner when cells were preincubated in the presence of 5-10 microM D-PDMP, but not with its stereoisomer L-PDMP. Closely associated with this growth-inhibitory effect in the presence of D-PDMP, levels of essentially all GSLs, including GM3 and other gangliosides, were greatly reduced, whereas ceramide accumulated. Importantly, metabolically labeled radioactive bands, corresponding to free sphingosine and N-monomethylsphingosine, were found to be present in very small quantities (5-12%) relative to the band corresponding to N,N-dimethylsphingosine (DMS), which showed significant accumulation in D-PDMP treated lymphocytes. The quantity of IL2 receptors and their affinity to IL2 on T cells did not change, but IL2-dependent tyrosine phosphorylation was greatly stimulated, following D-PDMP treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2207078 TI - Sequence-specific 1H NMR assignments and secondary structure in solution of Escherichia coli trp repressor. AB - Sequence-specific 1H NMR assignments are reported for the active L-tryptophan bound form of Escherichia coli trp repressor. The repressor is a symmetric dimer of 107 residues per monomer; thus at 25 kDa, this is the largest protein for which such detailed sequence-specific assignments have been made. At this molecular mass the broad line widths of the NMR resonances preclude the use of assignment methods based on 1H-1H scalar coupling. Our assignment strategy centers on two-dimensional nuclear Overhauser spectroscopy (NOESY) of a series of selectively deuterated repressor analogues. A new methodology was developed for analysis of the spectra on the basis of the effects of selective deuteration on cross-peak intensities in the NOESY spectra. A total of 90% of the backbone amide protons have been assigned, and 70% of the alpha and side-chain proton resonances are assigned. The local secondary structure was calculated from sequential and medium-range backbone NOEs with the double-iterated Kalman filter method [Altman, R. B., & Jardetzky, O. (1989) Methods Enzymol. 177, 218-246]. The secondary structure agrees with that of the crystal structure [Schevitz, R., Otwinowski, Z., Joachimiak, A., Lawson, C. L., & Sigler, P. B. (1985) Nature 317, 782], except that the solution state is somewhat more disordered in the DNA binding region and in the N-terminal region of the first alpha-helix. Since the repressor is a symmetric dimer, long-range intersubunit NOEs were distinguished from intrasubunit interactions by formation of heterodimers between two appropriate selectively deuterated proteins and comparison of the resulting NOESY spectrum with that of each selectively deuterated homodimer. Thus, from spectra of three heterodimers, long-range NOEs between eight pairs of residues were identified as intersubunit NOEs, and two additional long-range intrasubunits NOEs were assigned. PMID- 2207079 TI - Assignment of the backbone 1H and 15N NMR resonances of bacteriophage T4 lysozyme. AB - The proton and nitrogen (15NH-H alpha-H beta) resonances of bacteriophage T4 lysozyme were assigned by 15N-aided 1H NMR. The assignments were directed from the backbone amide 1H-15N nuclei, with the heteronuclear single-multiple-quantum coherence (HSMQC) spectrum of uniformly 15N enriched protein serving as the master template for this work. The main-chain amide 1H-15N resonances and H alpha resonances were resolved and classified into 18 amino acid types by using HMQC and 15N-edited COSY measurements, respectively, of T4 lysozymes selectively enriched with one or more of alpha-15N-labeled Ala, Arg, Asn, Asp, Gly, Gln, Glu, Ile, Leu, Lys, Met, Phe, Ser, Thr, Trp, Tyr, or Val. The heteronuclear spectra were complemented by proton DQF-COSY and TOCSY spectra of unlabeled protein in H2O and D2O buffers, from which the H beta resonances of many residues were identified. The NOE cross peaks to almost every amide proton were resolved in 15N edited NOESY spectra of the selectively 15N enriched protein samples. Residue specific assignments were determined by using NOE connectivities between protons in the 15NH-H alpha-H beta spin systems of known amino acid type. Additional assignments of the aromatic proton resonances were obtained from 1H NMR spectra of unlabeled and selectively deuterated protein samples. The secondary structure of T4 lysozyme indicated from a qualitative analysis of the NOESY data is consistent with the crystallographic model of the protein. PMID- 2207081 TI - Measurement of active-site homology between potato and rabbit muscle alpha-glucan phosphorylases through use of a linear free energy relationship. AB - The Michaelis-Menten parameters (Vmax and Km) for turnover of an extensive series of deoxy and deoxyfluoro derivatives of alpha-D-glucopyranosyl phosphate by the alpha-glucan phosphorylase from potato tuber have been determined. Very large rate reductions are observed as a consequence of each substitution, primarily due to losses in specific binding interactions, most likely hydrogen bonding, at the enzymic transition state. Comparison of the Vmax/Km values so determined with those measured for rabbit muscle alpha-glucan phosphorylase [Street et al. (1989) Biochemistry 28, 1581] reveals an astonishingly similar specificity, especially in light of the phylogenetic separation of their host organisms. This indicates that very similar hydrogen-bonding interactions between the enzyme and the substrate must be present at the transition states for the two enzymic reactions; therefore, they have very similar active sites. Quantitation of this similarity is achieved by plotting the logarithm of the Vmax/Km value for each substrate analogue with the potato enzyme against the same parameter for the muscle enzyme, yielding straight lines (p = 0.998 and 0.999) of slope 1.0 and 1.2 for the deoxy and deoxyfluoro substrates, respectively. Since the correlation coefficient of such plots is a direct measure of the similarity of the two transition-state complexes, thus of the enzyme active sites, it can be used as a measure of active site homology between the two enzymes. The extremely high homology observed in this case is consistent with the observed sequence homology at the active site. PMID- 2207080 TI - Substitution of Tyr254 with Phe at the active site of flavocytochrome b2: consequences on catalysis of lactate dehydrogenation. AB - A role for Tyr254 in L-lactate dehydrogenation catalyzed by flavocytochrome b2 has recently been proposed on the basis of the known active-site structure and of studies that had suggested a mechanism involving the initial formation of a lactate carbanion [Lederer, F., & Mathews, F.S. (1987) in Flavins and Flavoproteins, Proceedings of the Ninth International Symposium, Atlanta, GA, 1987 (Edmondson, D.E., & McCormick, D.B., Eds.) pp 133-142, Walter de Gruyter, Berlin]. This role is now examined after replacement of Tyr254 with phenylalanine. The kcat is decreased about 40-fold, Km for lactate appears unchanged, and the mainly rate-limiting step is still alpha-hydrogen abstraction, as judged from the steady-state deuterium isotope effect. Modeling studies with lactate introduced into the active site indicate two possible substrate conformations with different hydrogen-bonding partners for the substrate hydroxyl. If the hydrogen bond is formed with Tyr254, as was initially postulated, the mechanism must involve removal by His373 of the C2 hydrogen, with carbanion formation. If, in the absence of the Tyr254 phenol group, the hydrogen bond is formed with His373 N3, the substrate is positioned in such a way that the reaction must proceed by hydride transfer. Therefore the mechanism of the Y254F enzyme was investigated so as to distinguish between the two mechanistic possibilities. 2-Hydroxy-3-butynoate behaves with the mutant as a suicide reagent, as with the wild-type enzyme. Similarly, the mutant protein also catalyzes the reduction and the dehydrohalogenation of bromopyruvate under transhydrogenation conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2207082 TI - Comparison of the toxin binding sites of the nicotinic acetylcholine receptor from Drosophila to human. AB - Recombinant toxin binding proteins have been previously found to provide a convenient experimental system for the study of receptor-ligand recognition (Aronheim et al., 1988). Here, this system has been used to produce the binding sites of the cholinergic receptor derived from seven organisms, Torpedo californica, Xenopus, chick, mouse, calf, human, and Drosophila. These have been compared with respect to their toxin binding capacity. Scatchard analyses show that the KD values of alpha-bungarotoxin binding to the above sites are 63, 536, 150, 3200, 6200, 6470, and 1700 nM, respectively. These results reiterate the importance of alpha 183-204 as a ligand binding site. In order to increase the repertoire of sites available for study, chimeric structures were constructed. Through the analysis of such chimeras, some themes of the gross anatomy of the binding site can be learned. A positive subsite followed by a hydrophobic patch preceding a nucleophilic domain appears to be required for efficient toxin binding. PMID- 2207083 TI - Haloalkene oxidation by the soluble methane monooxygenase from Methylosinus trichosporium OB3b: mechanistic and environmental implications. AB - The soluble, three-protein component methane monooxygenase purified from Methylosinus trichosporium OB3b is capable of oxidizing chlorinated, fluorinated, and brominated alkenes, including the widely distributed ground-water contaminant trichloroethylene (TCE). The oxidation rates for the chloroalkenes were observed to be comparable to that for methane, the natural substrate, and up to 7000-fold higher than those reported for other well-defined biological systems. The competitive inhibitor tetrachloroethylene was found to be the only chlorinated ethylene not turned over. However, this appears to be due to steric effects rather than electronic effects or the lack of an abstractable proton because chlorotrifluoroethylene was efficiently oxidized. As evidenced by the formation of diagnostic adducts with 4-(p-nitrobenzyl)pyridine, the halogenated alkenes were oxidized predominantly by epoxidation. Stable acidic products resulting from subsequent hydrolysis were identified as the major products. However, additional aldehydic products resulting from intramolecular halide or hydride migration were observed in 3-10% yield during the oxidation of TCE, vinylidene chloride, trifluorethylene, and tribromoethylene. Product analysis of the hydrolysis reaction of authentic TCE epoxide showed little or no 2,2,2-trichloroacetaldehyde (chloral) formation, indicating that atomic migration occurred prior to product dissociation from the enzyme. The occurrence of atomic migration products shows that an intermediate in the substrate to product conversion carries significant cationic character. Such a species could be generated through interaction with a highly electron-deficient activated oxygen in the active site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2207084 TI - Kinetic investigation of the functional role of phenylalanine-31 of recombinant human dihydrofolate reductase. AB - The role of the active site residue phenylalanine-31 (Phe31) for recombinant human dihydrofolate reductase (rHDHFR) has been probed by comparing the kinetic behavior of wild-type enzyme (wt) with mutant in which Phe31 is replaced by leucine (F31L rHDHFR). At pH 7.65 the steady-state kcat is almost doubled, but the rate constant for hydride transfer is decreased to less than half that for wt enzyme, as is the rate of the obligatory isomerization of the substrate complex that precedes hydride transfer. Although steady-state measurements indicated that the mutation causes large increases in Km for both substrates, dissociation constants for many complexes are decreased. These apparent paradoxes are due to major mutation-induced decreases in rate constants (koff) for dissociation of folate, dihydrofolate, and tetrahydrofolate from all of their complexes. This results in a mechanism proceeding almost entirely by only one of the two pathways used by wt enzyme. Other consequences of these changes are a much altered dependence of steady-state kcat on pH, inhibition rather than activation by tetrahydrofolate, absence of hysteresis in transient-state kinetics, and a decrease in enzyme efficiency under physiological conditions. The results indicate that there is no quantitative correlation between dihydrofolate binding and the rate of hydride transfer for this enzyme. PMID- 2207085 TI - Effects of ions and pH on the thermal stability of thin and thick filaments of skeletal muscle: high-sensitivity differential scanning calorimetric study. AB - Differential scanning calorimetry (DSC) is unique for studying conformational changes in supramolecular structures because it is immune to interference by the turbidity and other optical artifacts of a sample solution. We have employed DSC to study thermal stability of myosin and actin in their filamentous forms (i.e., thick and thin filaments). The thermal stability of the myosin monomer, as well as polymers, showed remarkable sensitivities to pH and to the ionic strength of the solution. At pH 7.5, the endotherm of myosin filaments was broad and resembled that of the monomer in solution. Reducing the pH to 6.3 split the endotherm of the filament into two major transitions. The first one, with a Tm of 47 degrees C, a delta Hcal of 805 kcal/mol, and a cooperative ratio (CR) of 0.1, was relatively insensitive to the pH changes whereas the second one which represented approximately 80% of the helical structure was pH sensitive. The second transition released 2.17 H+ per mole at 0.17 M KCl and was defined by a Tm of 53.9 degrees C, a delta Hcal of 917 kcal/mol, and a CR of 0.35. The major fragment contributing to the splitting of the endotherm was interpreted to be S-2 because the Tm of purified S-2 in a similar medium also shifted from 39.5 degrees C at pH 7.3 to 49.6 degrees C at pH 6.0. KCl had similar effects on the shape of the endotherm of the thick filament. A decrease of KCl from 0.2 to 0.1 M enhanced the effect of pH on the second transition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2207086 TI - Study of effects of pH on the stability of domains in myosin rod by high resolution differential scanning calorimetry. AB - Differential scanning calorimetry (DSC) has detected at least six quasi independent structure domains in myosin rod [Potekhin, S.A., & Privalov, P.L. (1978) Biofizika 23, 219-223]. These domains were found to be remarkably sensitive to pH in the physiological range, i.e., pH 6-8. We compared the thermodynamic characteristics, and studied effects of pH on the stability, of individual domains in rod, light meromyosin (LMM), and subfragment 2 (S-2). In rod, the lowest stability domain (approximately 400 amino acid residues per double strand), with a Tm of 42.4 degrees C, a delta Hcal of 190 kcal/mol, and a delta G of 3.39 kcal/mol, at pH 7.02, destabilized by absorption of protons, is located at the LMM/S-2 junction and split into two parts, one associated with S-2 (approximately 100 residues per double strand) and the other with LMM (300 residues per double strand). The fragment with S-2 is likely a part of the "hinge" suggested by Swenson and Ritchie [(1980) Biochemistry 19, 5371-5375]. All other domains of rod released protons on melting. The domains located in S-2 were the most sensitive to pH and released a total of 0.9 proton on melting. The thermal meltings of all domains in myosin rod, LMM, and S-2 were independent of each other, and enthalpies of melting were additive in the whole pH range studied. Their sensitivities to pH and KCl were also unaffected by the presence or absence of other fragments. For example, domains in an isolated S-2 behaved similarly as they were in the rod, and so were domains in LMM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2207087 TI - Coupled changes between lipid order and polypeptide conformation at the membrane surface. A 2H NMR and Raman study of polylysine-phosphatidic acid systems. AB - Thermotropism and segmental chain order parameters of sn-2-perdeuteriated dimyristoyl-phosphatidic acid (DMPA)-water dispersions, with and without poly(L lysine) (PLL) of different molecular weights, have been investigated by solid state deuterium NMR spectroscopy. The segmental chain order parameter profile of this negatively charged lipid is similar to that already found for other lipids. Addition of long PLL (MW = 200,000) increases the temperature, Tc, of the lipid gel-to-fluid phase transition, whereas short PLL (MW = 4000) has practically no effect on Tc. In the fluid phase both varieties of PLL increase the "plateau" character of segmental order parameters up to carbon position 10. At the same reduced temperature, long PLL more significantly increases the segmental ordering, especially at the methyl terminal position. This leads to the conclusion that polar head-group capping and charge neutralization by PLL induce severe changes in lipid chain ordering, even down to the bilayer core. The structure of PLL bound to the lipid bilayer surface was monitored by Raman spectroscopy, following the amide I bands. Results show that the lipid gel-to fluid phase transition triggers a conformational transition from ordered beta sheet to random structure of short PLL, while it does not affect the strongly stabilized beta-sheet structure of long PLL. It is concluded that both short and long PLL can efficiently cap and neutralize lipid head groups, whatever their structure, and that peptide length is a key parameter in whether lipids or peptides are the driving force in conformationally coupled changes of both partners in the membrane. PMID- 2207088 TI - Bovine dopamine beta-hydroxylase, primary structure determined by cDNA cloning and amino acid sequencing. AB - A cDNA clone encoding bovine dopamine beta-hydroxylase (DBH) has been isolated from bovine adrenal glands. The clone hybridizes to two oligonucleotide probes, one based on a previously reported active site peptide [DeWolf, W. E., Jr., et al. (1988) Biochemistry 27, 9093-9101] and the other based on the human DBH sequence [Lamouroux, A., et al. (1987) EMBO J. 6, 3931-3937]. The clone contains a 1.9-kb open reading frame that codes for the soluble form of bovine DBH, with the exception of the first six amino acids. Direct confirmation of 93% of the cDNA-derived sequence was obtained from cleavage peptides by protein sequencing and mass spectrometry. Differences were found between these two sequences at only two positions. Of the four potential N-linked carbohydrate attachment sites, two, Asn-170 and Asn-552, were shown to be partially and fully glycosylated, respectively. Within the 69% of the protein sequence confirmed by mass spectrometry, no other covalent modifications were detected. PMID- 2207089 TI - Delineation of the functional site of a snake venom cardiotoxin: preparation, structure, and function of monoacetylated derivatives. AB - Toxin gamma, a cardiotoxin from the venom of the cobra Naja nigricollis, was modified with acetic anhydride, and the derivatives were separated by cation exchange and reverse-phase chromatography. Nine monoacetylated derivatives were obtained, and those modified at positions 1, 2, 12, 23, and 35 were readily identified by automated sequencing. The overall structure of toxin gamma, composed of three adjacent loops (I, II, and III) rich in beta-sheet, was not affected by monoacetylation as revealed by circular dichroic analysis. Trp-11, Tyr-22, and Tyr-51 fluorescence intensities were not affected by modifications at Lys-12 and Lys-35, whereas Trp-11 fluorescence intensity slightly increased when Lys-1 and Lys-23 were modified. The cytotoxic activity of toxin gamma to FL cells in culture was unchanged after modification at positions 1 and 2, whereas it was 3-fold lower after modification at Lys-23 and Lys-35. The derivative modified at Lys-12 was 10-fold less active than native toxin. Using two isotoxins, we found that substitutions at positions 28, 30, 31, and 57 did not change the cytotoxic potency of toxin gamma. A good correlation between cytotoxicity, lethality, and, to some extent, depolarizing activity on cultured skeletal muscle cells was found. In particular, the derivative modified at Lys-12 always had the lowest potency. Our data show that the site responsible for cytotoxicity, lethality, and depolarizing activity is not diffuse but is well localized on loop I and perhaps at the base of loop II. This site is topographically different from the AcChoR binding site of the structurally similar snake neurotoxins. PMID- 2207090 TI - Role of GTP hydrolysis in microtubule polymerization: evidence for a coupled hydrolysis mechanism. AB - The relationship between GTP hydrolysis and microtubule assembly has been investigated by using a rapid filtration method. Microtubules assembled from phosphocellulose-purified tubulin, double-labeled with [gamma-32P]- and [3H]GTP, were trapped and washed free of unbound nucleotide on glass fiber filters. The transient accumulation of microtubule-bound GTP predicted by uncoupled GTP hydrolysis models [Carlier & Pantaloni (1981) Biochemistry 20, 1918-1924; Carlier et al. (1987) Biochemistry 26, 4428-4437] during the rapid assembly of microtubules was not detectable under our experimental conditions. By calculating hypothetical time courses for the transient accumulation of microtubule-bound GTP, we demonstrate that microtubule-bound GTP would have been detectable even if the first-order rate constant for GTP hydrolysis were 4-5 times greater than the pseudo-first-order rate constant for tubulin subunit addition to microtubules. In a similar manner, we demonstrate that if GTP hydrolysis were uncoupled from microtubule assembly but were limited to the interface between GTP subunits and GDP subunits (uncoupled vectorial hydrolysis), then microtubule-bound GTP would have been detectable if GTP hydrolysis became uncoupled from microtubule assembly at less than 50 microM free tubulin, 5 times the steady-state tubulin concentration of our experimental conditions. In addition, during rapid microtubule assembly, we have not detected any microtubule-bound Pi, which has been proposed to form a stabilizing cap at the ends of microtubules [Carlier et al. (1988) Biochemistry 27, 3555-3559]. Also, several conditions that could be expected to increase the degree of potential uncoupling between GTP hydrolysis and microtubule assembly were examined, and no evidence of uncoupling was found. Our results are consistent with models that propose cooperative mechanisms that limit GTP hydrolysis to the terminal ring of tubulin subunits [e.g., O'Brien et al. (1987) Biochemistry 26, 4148-4156]. The results are also consistent with the hypothesis that a slow conformational change in tubulin subunits after GTP hydrolysis and Pi release occurs that results in destabilized microtubule ends when such subunits become exposed at the ends. PMID- 2207091 TI - Purification and characterization of clavaminate synthase from Streptomyces clavuligerus: an unusual oxidative enzyme in natural product biosynthesis. AB - A pivotal step in the biosynthetic pathway to the beta-lactamase inhibitor clavulanic acid is the conversion of proclavaminic acid to clavaminic acid in a reaction requiring Fe2+, alpha-ketoglutarate, and oxygen [Elson, S. W., Baggaley, K. H., Gillett, J., Holland, S., Nicholson, N. H., Sime, J. T., & Woroniecki, S. R. (1987) J. Chem. Soc., Chem. Commun., 1736-1738]. Clavaminate synthase, the enzyme that catalyzes this oxidative cyclization/desaturation, has been purified to homogeneity from clavulanic acid producing cells of Streptomyces clavuligerus (ATCC 27064). The enzyme behaved as a monomer during gel filtration and migrated with Mr 47,000 during denaturing gel electrophoresis. After ion-exchange FPLC two active forms of the protein were resolved that differed slightly in kinetic constants and apparent molecular weight. Kinetic comparisons with the four possible diastereomers of proclavaminate confirmed the absolute configuration of the substrate to be 2S,3R. The stoichiometry of the overall transformation was determined to be proclavaminate + 2(alpha-ketoglutarate) + 2O2----clavaminate + 2(succinate) + 2CO2 + 2H2O. In the absence of proclavaminate a slow decarboxylation of alpha-ketoglutarate to succinate and CO2 was observed in an uncoupled reaction which resulted in enzyme inactivation. Steady-state kinetic studies were undertaken for an initial description of the enzyme's catalytic cycle. The double-reciprocal plot with alpha-ketoglutarate as the variable substrate was linear; this supports the proposal that two stepwise oxidations of proclavaminate occur, each with the consumption of alpha-ketoglutarate and oxygen and the release of succinate, CO2, and H2O. The intersecting initial velocity plots obtained from pairwise variation of substrate concentrations were consistent with a sequential kinetic mechanism for the first oxidation. Similarities observed between clavaminate synthase and alpha-ketoglutarate dependent dioxygenases argue for a common mechanism of oxygen activation. However, the nature of the interactions of the substrates in the active site of clavaminate synthase apparently redirects the conventional hydroxylase activity of dioxygenases to the construction of a strained bicyclic skeleton driven by the overall reduction of dioxygen. PMID- 2207092 TI - Base stacking and unstacking as determined from a DNA decamer containing a fluorescent base. AB - Time-resolved fluorescence decay of a single-stranded DNA decamer d(CTGAAT5CAG), where d5 is the fluorescent base 1-(beta-D-2'-deoxyribosyl)-5-methyl-2 pyrimidinone, was measured and analyzed at several temperatures. The d5 base in the decamer is resolved into three states according to their fluorescence decay lifetime characteristics and temperature dependence of their associated amplitudes: fully extended and completely unstacked state, loosely associated state, and fully stacked state. These states are in slow exchange compared to their fluorescence decay rates. The population of the fully extended and completely unstacked state is small and decreases further with increasing temperature. The loosely associated state, whose fluorescence can still be efficiently quenched by other DNA bases, occupies a large portion of the conventionally defined unstacked state. Stacking enthalpy and entropy for the d5 base with thymine or cytosine bases in the DNA decamer are calculated to be -6.6 kcal/mol and -22 cal/mol.K, respectively. This work shows that fluorescent bases in DNA can be useful to the study of local conformations of bases. PMID- 2207093 TI - Anomalous gel migration of DNA oligomers containing multiple conformational junctions. AB - We have previously shown that a short 16 base pair DNA oligomer can accommodate a B-Z conformational junction [Sheardy, R. D., & Winkle, S. A. (1989) Biochemistry 28, 720-725]. Results from 1H NMR studies indicated that only three base pairs were involved in the junction and that one of these base pairs was highly distorted. Being interested in the nature of this distortion, we constructed DNA oligomers which have the potential to contain multiple B-Z junctions for polyacrylamide electrophoretic studies. We report that the mobilities displayed by these molecules through acrylamide gels in the absence and presence of cobalt suggest that these molecules run shorter than they actually are. This anomalous migration may be due to structural/dynamic properties of the DNA helix manifested by the periodic distortions of the potential B-Z junctions. PMID- 2207094 TI - NMR studies of the interaction of chromomycin A3 with small DNA duplexes. Binding to GC-containing sequences. AB - The interaction of chromomycin A3 with the oligodeoxyribonucleotides 1, d(ATGCAT), 2, d(ATCGAT), 3, d(TATGCATA), and 4, d(ATAGCTAT), has been investigated by 1H and 31P NMR. In the presence of Mg2+, chromomycin binds strongly to the three GC-containing oligomers 1, 3, and 4 but not to the CG containing oligomer 2. The proton chemical shift changes for 1 and 3 are similar, and these DNA duplexes appear to bind with a stoichiometry of 2 drugs:1 Mg2+:1 duplex. The same stoichiometry of 2 drugs:1 duplex is confirmed with 4; however, proton chemical shift changes differ. An overall C2 symmetry is exhibited by the drug complex with 1, 3, and 4. At a molar ratio of 2.0 (drugs:duplex), no free DNA proton NMR signals remain. Two-dimensional nuclear Overhauser exchange spectroscopy (NOESY) of the saturated chromomycin complex with 1 and 3 positions both chromomycinone hydroxyls and the E carbohydrates in the minor groove and provides evidence suggesting that the B carbohydrates lie on the major-groove side. This is supported by several dipolar coupling cross-peaks between the drug and the DNA duplex. Drug-induced conformational changes in duplex 1 are evaluated over a range of NOESY mixing times and found to possess some characteristics of both B-DNA and A-DNA, where the minor groove is wider and shallower. A widening of the minor groove is essential for the DNA duplex to accommodate two drug molecules. This current minor-groove model is a substantial revision of our earlier major-groove model [Keniry, M.A., Brown, S.C., Berman, E., & Shafer, R.H. (1987) Biochemistry 26, 1058-1067] and is in agreement with the model recently proposed by Gao and Patel [Gao, X., & Patel, D. J. (1989a) Biochemistry 28, 751 762]. PMID- 2207095 TI - Minimum secondary structure requirements for catalytic activity of a self splicing group I intron. AB - We have completed a comprehensive deletion analysis of the Tetrahymena ribozyme in order to define the minimum secondary structure requirements for phosphoester transfer activity of a self-splicing group I intron. A total of 299 nucleotides were removed in a piecewise fashion, leaving a catalytic core of 114 nucleotides that form 7 base-paired structural elements. Among the various deletion mutants are a 300-nucleotide single-deletion mutant and a 281-nucleotide double-deletion mutant whose activity exceeds that of the wild type when tested under physiologic conditions. Consideration of those structural elements that are essential for catalytic activity leads to a simplified secondary structure model of the catalytic core of a group I intron. PMID- 2207096 TI - Dominant forces in protein folding. PMID- 2207097 TI - Identification and properties of the catalytic domain of mammalian DNA polymerase beta. AB - Rat DNA polymerase beta (beta-pol) is a 39-kDa protein organized in two tightly folded domains, 8-kDa N-terminal and 31-kDa C-terminal domains, connected by a short protease-sensitive region. The 8-kDa domain contributes template binding to the intact protein, and we now report that the 31-kDa C-terminal domain contributes catalytic activity. Our results show that this domain as a purified proteolytic fragment conducts DNA synthesis under appropriate conditions but the kcat is lower and primer extension properties are different from those of the intact enzyme. A proteolytic truncation of the 31-kDa catalytic domain fragment, to remove a 60-residue segment from the NH2-terminal end, results in nearly complete loss of activity, suggesting the importance of this segment. Overall, these results indicate that the domains of beta-pol have distinct functional roles, template binding and nucleotidyltransferase, respectively; yet, the intact protein is more active for each function than the isolated individual domain fragment. PMID- 2207098 TI - 1H NMR studies of human lysozyme: spectral assignment and comparison with hen lysozyme. AB - Complete main-chain (NH and alpha CH) 1H NMR assignments are reported for the 130 residues of human lysozyme, along with extensive assignments for side-chain protons. Analysis of 2-D NOESY experiments shows that the regions of secondary structure for human lysozyme in solution are essentially identical with those found previously in a similar study of hen lysozyme and are in close accord with the structure of the protein reported previously from X-ray diffraction studies in the crystalline state. Comparison of the chemical shifts, spin-spin coupling constants, and hydrogen exchange behavior are also consistent with closely similar structures for the two proteins in solution. In a number of cases specific differences in the NMR parameters between hen and human lysozymes can be correlated with specific differences observed in the crystal structures. PMID- 2207099 TI - Determination of the conformation of d(GGAAATTTCC)2 in solution by use of 1H NMR and restrained molecular dynamics. AB - The conformation of the putative bent DNA d(GGAAATTTCC)2 in solution was studied by use of 1H NMR and restrained molecular dynamics. Most of the resonances were assigned sequentially. A total of 182 interproton distance restraints were determined from two-dimensional nuclear Overhauser effect spectra with short mixing times. Torsion angle restraints for each sugar moiety were determined by qualitative analysis of a two-dimensional correlated spectrum. Restrained molecular dynamics was carried out with the interproton distances and torsion angles incorporated into the total energy function of the system in the form of effective potential terms. As initial conformations for restrained molecular dynamics, classical A-DNA and B-DNA were adopted. The root mean square deviation (rmsd) between these two conformations is 5.5 A. The conformations obtained by use of restrained molecular dynamics are very similar to each other, the rmsd being 0.8 A. On the other hand, the conformations obtained by use of molecular dynamics without experimental restraints or restrained energy minimization depended heavily on the initial conformations, and convergence to a similar conformation was not attained. The conformation obtained by use of restrained molecular dynamics exhibits a few remarkable features. The second G residue takes on the BII conformation [Fratini, A. V., Kopka, M. L., Drew, H. R., & Dickerson, R. E. (1982) J. Biol. Chem. 257, 14686-14707] rather than the standard BI conformation. There is discontinuity of the sugar puckering between the eighth T and ninth C. The minor groove of the oligo(dA) tract is rather compressed. As a result, d(GGAAATTTCC)2 is bent. PMID- 2207100 TI - Ultraviolet-induced thymine hydrates in DNA are excised by bacterial and human DNA glycosylase activities. AB - Ultraviolet irradiation of DNA results in various pyrimidine modifications. We studied the excision of an ultraviolet thymine photoproduct by Escherichia coli endonuclease III and by a preparation of human WI-38 cells. These enzymes cleave UV-irradiated DNA at apyrimidinic sites formed by glycosylic removal of the photoproduct. Poly(dA-[3H]dT).poly(dA-[3H]dT) was UV irradiated and incubated with purified E. coli endonuclease III. 3H-Containing material was released in a manner consistent with Michaelis-Menten kinetics. This 3H-labeled material was determined to be a mixture of thymine hydrates (6-hydroxy-5,6-dihydrothymine), separable from unmodified thymine by chromatography in three independent systems. Both cis-thymine hydrate and trans-thymine hydrate were chemically and photochemically synthesized. These coeluted with the enzyme-released 3H containing material. No thymine glycol was released from the UV-irradiated polymer. Similar results were obtained with extracts of WI-38 cells as the enzyme source. The release of thymine hydrates by both glycosylase activities was directly proportional to the amount of enzyme and the irradiation dose to the DNA substrate. These results demonstrate the modified thymine residues recognized and excised by endonuclease III and the human enzyme to be a mixture of cis-thymine hydrate and trans-thymine hydrate. The reparability of these thymine hydrates suggests that they are stable in DNA and therefore potentially genotoxic. PMID- 2207101 TI - Stabilization of Z-DNA by demethylation of thymine bases: 1.3-A single-crystal structure of d(m5CGUAm5CG). AB - Methylation of cytosine bases at the C5 position has been known to stabilize Z DNA. We had previously predicted from calculations of solvent-accessible surfaces that the methyl group at the same position of thymine has a destabilizing effect on Z-DNA. In the current studies, the sequence d(m5CGUAm5CG) has been crystallized and its structure solved as Z-DNA to 1.3-A resolution. A well defined octahedral hexaaquomagnesium complex was observed to bridge the O4 oxygens of the adjacent uridine bases at the major groove surface, and four well structured water molecules were found in the minor groove crevice at the d(UA) dinucleotide. These solvent interactions were not observed in the previously published Z-DNA structure of the analogous d(m5CGTAm5CG) sequence. A comparison of the thymine and uridine structures supports our prediction that demethylation of thymine bases helps to stabilize Z-DNA. A comparison of this d(UA)-containing Z-DNA structure with the analogous d(TA) structure shows that access of the O4 position is hindered by the C5 methyl of thymine due to steric and hydrophobic inhibition. In the absence of the methyl group, a magnesium-water complex binds to and slightly affects the structure of the Z-DNA major groove surface. This perturbation of the solvent structure at the major groove surface is translated into a much larger 1.41-A widening of the minor groove crevice, thereby allowing the specific binding of two water molecules at well-defined sites of each internal d(UA) base pair. Possible mechanisms by which modifications at the major groove surface of Z-DNA can affect the solvent properties of the minor groove crevice are discussed. PMID- 2207102 TI - Cloning, sequence determination, and expression of the genes encoding the subunits of the nickel-containing 8-hydroxy-5-deazaflavin reducing hydrogenase from Methanobacterium thermoautotrophicum delta H. AB - The genes frhA (1217 bp), frhB (845 bp), and frhG (710 bp) encoding the three known subunits, alpha, beta, and gamma, of the 8-hydroxy-5-deazaflavin (F420) reducing hydrogenase (FRH) from the thermophilic methanogen Methanobacterium thermoautotrophicum delta H have been cloned, sequenced, and shown to be tightly linked, indicative of a single transcriptional unit. The DNA sequence contains a fourth open reading frame, designated frhD (476 bp), encoding a polypeptide (delta) that does not copurify with the active enzyme. Expression of the frh gene cluster in Escherichia coli shows that four polypeptides are synthesized. When analyzed by SDS-PAGE, the proteins migrate with mobilities consistent with their calculated molecular weights. In order to understand the mechanism of H2 oxidation by this enzyme, localization of redox cofactors (Ni, Fe/S, FAD) to specific subunits and information on their structure is needed. This has been hindered due to the refractory nature of the enzyme to denaturation methods needed in order to obtain individual subunits with cofactors intact. In this paper we discuss the possible localization of the redox cofactors as implicated from the DNA-derived protein sequences of the subunits. The amino acid sequences of the subunits of the FRH are compared with those of other Ni-containing hydrogenases, including the methyl viologen reducing hydrogenase (MVH) of M. thermoautotrophicum delta H. PMID- 2207103 TI - Spontaneous incorporation of bacteriorhodopsin into large preformed vesicles. AB - Bacteriorhodopsin, either as purple membrane sheets or as detergent-solubilized protein, was found to incorporate spontaneously into both large unilamellar vesicles (LUVs) and sized multilamellar vesicles (MLVs) under either gel-phase or liquid-phase conditions. These results were obtained with LUVs of various lipid compositions, including dimyristoylphosphatidylcholine (DMPC), DMPC and cholesterol, dioleoylphosphatidylcholine (DOPC), and DOPC and cholesterol. The lipid to protein (L/P) ratio of all proteoliposomes arising from these preformed vesicles continually increased in the presence of protein-free vesicles. Under fluid-phase conditions, the mixing of LUVs of DMPC with proteoliposomes showed vesicle growth independent of lipid concentration, suggesting that growth was due to lipid transfer. However, under gel-phase conditions a more rapid, concentration-dependent increase in the L/P ratio of the proteoliposome was observed, suggesting that growth occurred by a mechanism other than lipid transfer from vesicles to proteoliposomes. The use of the proteoliposome as an artificial lipid-protein membrane model is discussed. PMID- 2207104 TI - Damage repertoire of the Escherichia coli UvrABC nuclease complex includes abasic sites, base-damage analogues, and lesions containing adjacent 5' or 3' nicks. AB - Using oligonucleotide synthesis, we demonstrate a rapid and efficient method for the construction of DNA duplexes containing defined DNA lesions at specific positions. These DNA lesions include apyrimidinic sites, reduced apyrimidinic sites, and base-damage analogues consisting of O-methyl- or O-benzylhydroxylamine modified apyrimidinic sites. A 49 base pair DNA duplex containing these lesions was specifically incised by the UvrABC nuclease complex. The incision sites occurred predominantly at the eighth phosphodiester bond 5' and the fifth phosphodiester bond 3' to the lesion. Multiple incisions were observed 3' to the lesion. The extent of DNA incisions was base-damage analogues greater than reduced apyrimidinic sites greater than apyrimidinic sites. Introduction of 3' or 5' nicks at the site of a base-damage analogue by treatment of these substrates with either endonuclease III or endonuclease IV reduced, but did not abolish, subsequent incision by the UvrABC complex, whereas introduction of a 3' nick at an abasic site increased the incision efficiency of the UvrABC complex. These data demonstrate a convergence of base and nucleotide excision repair pathways in the removal of specific base damages. PMID- 2207105 TI - Evaluation of selected benzoquinones, naphthoquinones, and anthraquinones as replacements for phylloquinone in the A1 acceptor site of the photosystem I reaction center. AB - Selected substituted 1,4-benzoquinones, 1,4-naphthoquinones, and 9,10 anthraquinones were investigated as possible replacement quinones in spinach photosystem I (PSI) preparations that had been depleted of endogenous phylloquinone by extraction with hexane/methanol. As a criterion for successful biochemical reconstitution, the restoration of electron transfer was determined by measuring P-430 turnover at room temperature from flash-induced absorbance transients. Restoration of complete electron transfer between A0- and P-430 (terminal iron-sulfur centers, FAFB) was demonstrated by using phylloquinone, 2 methyl-3-decyl-1,4-naphthoquinone, 2-methyl-3-(isoprenyl)2-1,4-naphthoquinone, and 2-methyl-3-(isoprenyl)4-1,4-naphthoquinone. All other quinones tested did not restore P-430 turnover but acted as electron acceptors and oxidized A0-. It is concluded that the specificity of the replacement quinone for interaction with the primary acceptor, A0-, is low but additional structural constraints are required for the quinone occupying the A1 site to donate to the iron-sulfur center, Fx. It is suggested that the 3-phytyl side chain of phylloquinone and the 3-alkyl tails of the three naphthoquinones that restored P-430 turnover may be required for interaction with a hydrophobic domain of the A1 site in the PSI core to promote electron transfer to Fx and then to FAFB. PMID- 2207106 TI - Role of membrane lipids in the interaction of daunomycin with plasma membranes from tumor cells: implications in drug-resistance phenomena. AB - Equilibrium binding studies on the interaction between the anthracycline daunomycin and plasma membrane fractions from daunomycin-sensitive and -resistant murine leukemia P-388 cells are presented. Drug binding constants (KS) are 15,000 and 9800 M-1 for plasma membranes from drug-sensitive and drug-resistant cells, respectively. Drug binding to the membranes is not affected by either (i) thermal denaturation of membrane proteins or (ii) proteolytic treatment with trypsin, thus suggesting that the protein components of the membranes do not have a major role in determining the observed drug binding. Also, fluorescence resonance energy transfer between tryptophan and daunomycin in the membranes indicates that interaction of protein components with the drug should not be responsible for the observed differences in drug binding exhibited by plasma membranes from drug sensitive and -resistant cells. Plasma membranes from drug-sensitive cells contain more phosphatidylserine and slightly less cholesterol than membranes from drug-resistant cells. Differences in the content of the acidic phospholipid between the two plasma membranes seem to produce a different ionic environment at membrane surface domains, as indicated by titration of a membrane-incorporated, pH-sensitive fluorescence probe. The possible role of membrane lipids in modulating drug binding to the membranes was tested in equilibrium binding studies using model lipid vesicles made from phosphatidylcholine, phosphatidylserine, and cholesterol in different proportions. The presence of phosphatidylserine greatly increases both the affinity and the stoichiometry of daunomycin binding to model lipid vesicles. The similarity between the effects of phosphatidylserine and other negatively charged compounds such as dicetyl phosphate, cardiolipin, or phosphatidic acid suggests that electrostatic interactions are important in the observed binding of the drug.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2207107 TI - Interactions of short-chain alcohols with dimyristoylphosphatidylethanolamine bilayers: a calorimetric and infrared spectroscopic investigation. AB - We have investigated the effects of methanol, ethanol, and 1-propanol on the phase transitions of L-alpha-dimyristoylphosphatidylethanolamine using differential scanning calorimetry and Fourier transform infrared spectroscopy. Alcohols lower the temperature of the gel (L beta) to liquid-crystalline (L alpha) phase transition and also lower the temperature of the unhydrated crystalline (Lc) to liquid-crystalline phase transition. When the lipid/alcohol dispersions are incubated at 2 degrees C for 1-18 h, a dehydrated crystalline phase forms, which gives rise to a phase transition at about 55 degrees C. This dehydrated crystalline phase forms more quickly at higher alcohol concentrations. Although alcohol at low concentration lowers the enthalpy of the observed melting transition, at high concentrations 1-propanol markedly increases this enthalpy. The phase giving rise to this high-enthalpy melting process is distinct from both the unhydrated crystalline phase and the gel phase. Infrared spectra suggest that this phase contains significant amounts of alcohol in a solid solution with the lipid. PMID- 2207108 TI - A calcium-specific conformational response of parvalbumin. AB - The single tryptophan containing isotype III parvalbumin from codfish (Gadus callarius) was purified by a modified procedure and was shown to be homogeneous by a number of biochemical techniques. Sequence analysis established the location of the single tryptophan in position 102 of the 108 amino acid primary sequence. Atomic absorption spectroscopy showed that trichloroacetic acid (TCA) precipitation was more effective in parvalbumin decalcification compared to the more commonly used method of EGTA treatment. Magnesium induced steady-state fluorescence spectral changes of the EGTA-treated, but not the TCA-treated, parvalbumin. Steady-state fluorescence and circular dichroism spectra showed that calcium, but not magnesium, induced a conformational response in the TCA-treated protein. The fluorescence decay of the calcium-loaded native (holo) cod III parvalbumin was best described by two decay time components. By contrast, three lifetime components were necessary to describe the fluorescence decay of the metal-free (apo) protein. The decay-associated spectra of each temporal component were obtained. Collectively, these results demonstrate that it is possible for a parvalbumin to display a calcium-specific response. PMID- 2207109 TI - Recombinant chymotrypsin inhibitor 2: expression, kinetic analysis of inhibition with alpha-chymotrypsin and wild-type and mutant subtilisin BPN', and protein engineering to investigate inhibitory specificity and mechanism. AB - The serine protease inhibitor chymotrypsin inhibitor 2 (CI2 or BSPI2) has been expressed in Escherichia coli with the pINIIIompA3 expression vector to produce 20-40 mg/L of culture. Recombinant CI2 purified from this system has been characterized and found to be identical with CI2 from barley. Slow-binding kinetics were observed for the interaction between CI2 and subtilisin BPN', with Ki = 2.9 x 10(-12) M. Analysis of slow-binding data indicates that binding of the inhibitor follows the simplest model of E + I = EI with no kinetically detectable intermediate steps or proteolytic cleavage of the reactive site bond in CI2 (Met 59-Glu-60). This, in agreement with crystallographic data, indicates that the enzyme-inhibitor adduct is the Michaelis complex, which is not chemically processed by the enzyme. Three mutant CI2 molecules with new P1 residues have also been examined with a range of serine proteases, including a mutant subtilisin. In agreement with earlier studies, we find the P1 amino acid an important determinant of specificity. CI2 Met----Lys-59 was found to be a temporary inhibitor of subtilisin BPN' but an effective inhibitor of subtilisin Carlsberg and subtilisin BPN'(Glu----Ser-156). The structural reasons for this are discussed in relation to mechanisms of inhibition of serine proteases. PMID- 2207110 TI - The rapidly phosphorylated 25 kDa polypeptide of the light- harvesting complex of photosystem II is encoded by the type 2 cab-II genes. AB - The main light-harvesting complex of Photosystem II (LHC II) in higher plants consists of two sub-populations. The 'inner' pool consists only of a 27 kDa polypeptide, whereas in the 'outer' pool both the 27 kDa and a 25 kDa polypeptide are found. We purified the 25 and the 27 kDa LHC II polypeptides from Scots pine and 25 kDa LHC II polypeptide from spinach. Protein sequencing after cleavage with endoproteinase Lys-C showed that the 25 kDa polypeptide is encoded by the Type 2 cab-II genes and the 27 kDa polypeptide by the Type I cab-II genes. A fatty acid was not covalently attached to the peptides assembled into the pigment protein complex. Our results show that the different polypeptides seen on a gel are different gene products, and not the result of different processing. PMID- 2207111 TI - Differentiation between leaks and slips in oxidative phosphorylation. AB - We have measured the thermodynamic efficiency of oxidative phosphorylation of isolated rat-liver mitochondria during oxidation of succinate. Furthermore, we have calculated what the effect of proton leak or slip in the redox pumps should be on the efficiency of energy transduction in oxidative phosphorylation. These calculations were compared with experiments in which the efficiency was determined in the presence of induced proton leak or redox slip. The results of these experiments are in agreement with the predictions. It is concluded that it is possible to distinguish experimentally between effects of proton leak and redox slip on energy transduction. PMID- 2207112 TI - Stimulation of phosphate transport in rat-liver mitochondria by thyroid hormones. AB - The effect of hyperthyroidism on the transport of phosphate in rat-liver mitochondria has been examined. Thyroid hormones administered in vivo increased carrier mediated (mersalyl-sensitive) phosphate transport. Kinetic analysis of the phosphate transport showed that the thyroid hormone affects the Vmax of this process, while having no effect on the Km values. The higher activity of the phosphate carrier was found not to be due to a change in the endogenous content of phosphate nor to a change in the transmembrane delta pH value. Inhibitor titrations with mersalyl showed that mitochondria from both control and hyperthyroid rats required the same concentrations of inhibitor to produce total inhibition of phosphate transport, thus suggesting that the amount of functional translocase present is unaffected. The level of cardiolipin was significantly higher in mitochondrial membranes from hyperthyroid rats as compared to the control rats. The thyroid hormone induced change in the activity of the phosphate carrier appears to be due to a more favorable lipid microenvironment (cardiolipin content) surrounding the carrier molecule in the mitochondrial membrane. PMID- 2207113 TI - Effect of cyclosporin A on the membrane potential and Ca2+ level of human lymphoid cell lines and mouse thymocytes. AB - The effect of the immunosuppressive cyclosporin A (CsA) on the cytosolic free Ca2+ concentration ([Ca2+]i) and membrane potential of human B and T lymphoblastoid cells and mouse thymocytes was studied in order to reveal some features of the early stage of drug-cell interaction. Cytosolic free Ca2+ concentration of the cells was measured by spectrofluorimetry using indo-1 and quin2 fluorescent calcium indicators. Membrane potential was monitored in a flow cytometer with oxonol dye. CsA applied at 2-20 micrograms/ml final concentrations caused a dose-dependent, rapid, transient rise of [Ca2+]i in all cell types. This effect could be blocked by chelating the extracellular Ca2+ with EGTA but was not sensitive to Ca2+ channel blockers verapamil and nifedipine or K+ channel blocker 4-aminopyridine. A possible explanation for the calcium mobilizing effect of CsA is an ionophore-like mode of action at the cell membrane level. Besides directly interfering with mitogenic signals, the elevation of [Ca2+]i could be responsible for an initial hyperpolarization observed in CsA-treated T lymphocytes. This hyperpolarization, however, was not detectable in B lymphoblastoid cells. A further difference between B and T cells was the diverse pattern of depolarization following CsA treatment. This variance in the behaviour of T and B lymphocytes and the diversity of membrane transport systems in its background could account for the different final outcome of the drug-cell interaction. PMID- 2207114 TI - Biothermokinetics of processes and energy conversion. PMID- 2207115 TI - Kinetic characterization of the reconstituted tricarboxylate carrier from rat liver mitochondria. AB - The tricarboxylate carrier from rat liver mitochondria was purified by chromatography on hydroxyapatite/celite and reconstituted in phospholipid vesicles by removing the detergent using hydrophobic chromatography on Amberlite. Optimal transport activity was obtained by using a Triton X-114/phospholipid ratio of 0.8, 6% cardiolipin and 24 passages through a single Amberlite column. In the reconstituted system the incorporated tricarboxylate carrier catalyzed a first-order reaction of citrate/citrate or citrate/malate exchange. The activation energy of the exchange reaction was 70.1 kJ/mol. The rate of the exchange had a pH optimum between 7 and 8. The half-saturation constant was 0.13 mM for citrate and 0.76 mM for malate. All these properties were similar to those described for the tricarboxylate transport system in intact mitochondria. In proteoliposomes the maximum exchange rate at 25 degrees C reached 2000 mumols/min per g protein. This value was independent of the type of substrate present at the external or internal space of the liposomes (citrate or malate). PMID- 2207116 TI - Alterations in red blood cell sugar transport by nanomolar concentrations of alkyl lysophospholipid. AB - Acyl lysolipids presented in vitro to red blood cells in amounts comparable to blood serum levels inhibit protein-mediated glucose transport (Naderi, A., Carruthers, A. and Melchior, D.L. (1989) Biochim. Biophys. Acta 985, 173-181). In this study, an alkyl lysolipid (2-O-methyl-1-O-octadecyl-sn-glycero-3- phosphocholine; ALP), was found to be an order of magnitude more effective in inhibiting sugar transport than the most potent acyl lysolipid. Bilayer concentrations of ALP as low as 5 ALP molecules per transporter (0.1 mol% of total membrane lipid) result in a 50% inhibition of transport activity. ALP acts as a competitive inhibitor of exchange L-glucose transport, of CCB binding to the glucose transporter and of D-glucose inhibition of CCB binding to the transporter. Inhibition of zero-trans sugar uptake by ALP is noncompetitive. The two enantiomers of ALP show a different ability to inhibit sugar transport. The action of ALP is consistent with a mechanism in which ALP interacts with a transmembrane portion of the sugar transport molecule resulting in a competitive displacement of D-glucose or cytochalasin B from the cytosolic facing side of the transport molecule. The simplest explanation of our findings is a direct interaction of the ALP molecule with the transport protein. PMID- 2207117 TI - Surface exposure of phosphatidylserine is associated with the swelling and osmotically-induced fusion of human erythrocytes in the presence of Ca2+. AB - An assay for procoagulant activity has been used to investigate the Ca2(+) dependent exposure of phosphatidylserine at the surface of human erythrocytes that were induced to swell and to fuse osmotically. Since the phosphatidylserine of human erythrocytes is located in the inner leaflet of the plasma membrane, it is inaccessible in intact cells which therefore had no procoagulant activity in an isotonic solution of sucrose. The procoagulant activity of erythrocytes incubated in increasingly hypotonic, sucrose solutions containing Mg2+ paralleled the percentage haemolysis, reflecting the accessibility of phosphatidylserine in an increasing number of lysed cells. However, cells in mildly hypotonic sucrose solutions containing Ca2+ had an abnormally high procoagulant activity indicating that phosphatidylserine was exposed in intact cells under these conditions. Erythrocytes that were subjected to continuous swelling at 37 degrees C, which was induced by entry of the permeant molecule poly(ethylene glycol) 400 (PEG 400) developed procoagulant activity in the presence of Ca2+ prior to extensive lysis. Cells treated in this way also fused. With Mg2+, PEG 400-treated erythrocytes lysed without fusing, and the development of procoagulant activity paralleled the rate of lysis. Erythrocytes incubated with ionophore A23187, subtilisin, and Ca2+ developed procoagulant activity (with less than 20% lysis), and they fused on subsequent exposure to a hypotonic medium. The procoagulant activity reached its maximum before fusion could be induced in the hypotonic medium. It is concluded that the entry of Ca2+ facilitates a translocation of phosphatidylserine to the outer leaflet of the erythrocyte plasma membrane that plays an important role in fusion protocols that involve cell swelling. It is also suggested that transbilayer movements of phosphatidylserine could be an important control factor in the cell biology of membrane fusion phenomena. PMID- 2207118 TI - Transport of a large neutral amino acid (phenylalanine) in a human intestinal epithelial cell line: Caco-2. AB - We have characterized the transcellular transport of a large neutral amino acid (LNAA) in Caco-2 cell monolayers. The apical (AP) to basolateral (BL) transport of phenylalanine (Phe) was approximately 10-times faster than BL-to-AP transport. The evidence for the carrier-mediated AP-to-BL transport of Phe include: (a) temperature dependence and saturability, (b) Phe transport was not affected by a reverse gradient, (c) the activation energy for transport was 12.0 kcal/mol, and (d) an excess amount of unlabeled Phe caused a 75% reduction in transport rate and a delay (lag time) in the appearance of Phe in the BL side. The Vm and Km for Phe transport were 572.4 pmol.mg protein-1.min-1 and 0.56 mM, respectively. Phe transport was decreased in the absence of glucose and in the presence of sodium azide or ouabain. The carrier interacted with LNAAs and with cationic amino acids but not with small neutral or anionic amino acids. PMID- 2207119 TI - The conformation of pyrethroids bound to lipid bilayers. AB - A number of pyrethroids have been synthesised containing bromine or iodine atoms in the acid and alcohol moieties. Quenching of the fluorescence of a pyrene containing fatty acid in phospholipid bilayers has been used to measure the partitioning of the pyrethroids into the bilayers. Comparison of the intensity of the fluorescence of the 3-phenoxybenzyl moiety of the pyrethroids in lipid bilayers with that in organic solvents shows that the 3-phenoxybenzyl moiety is located in a hydrophobic environment; this was confirmed by fluorescence quenching by spin-labelled fatty acids. Self-quenching of the fluorescence of pyrethroids which contain both a bromine-containing acid and a 3-phenoxybenzyl moiety is consistent with a 'horseshoe' conformation for the bound pyrethroid, with the ester group located at the lipid/water interface and the acid and alcohol moieties folded back with both penetrating into the lipid bilayer. PMID- 2207120 TI - Effects of culture and incubation conditions on membrane fluidity in monolayers of cultured cells measured as fluorescence anisotropy using trimethylammoniumdiphenylhexatriene (TMA-DPH). AB - Membrane fluidity of coverslip attached living cells was measured as fluorescence anisotropy using 5 microM trimethylammoniumdiphenylhexatriene (TMA-DPH) as fluorescent probe. Fluorescence anisotropy is inversely related to membrane fluidity. Cells were grown on glass coverslips that were inserted and directly incubated in quarz cuvettes. The coverslips were fixed with special holders at an angle of 30 degrees in respect to the incident light. Effects of incubation temperature, of cell growth and densities and of the ionic and nonionic composition of the incubation medium on membrane fluorescence anisotropy were measured. Membranes of growing cells were more fluid than those of stationary cells, while cell densities had no effect except at very low cell numbers. Calcium concentrations increasing from 0 to 8 mmol/l in the incubation medium proportionally decreased membrane fluidity. Hypotonicity of the incubation media increased membrane fluidity while hypertonicity compared to normotonicity had no effect. Differentiated human fibroblasts from different origins exhibited similar membrane fluidities. They were, however, different from those of rat cells. Membrane fluidity of rat brain tumor cells increased with age in culture while membrane fluidity of primary differentiating rat brain cells decreased in with age in culture. Measurement of fluorescence anisotropy in living cells attached to glass coverslips is a convenient tool to study effects of culture--as well as of environmental--conditions on membrane fluidity. PMID- 2207121 TI - Protein-liposome conjugates with defined size distributions. AB - Conjugation of protein to liposomes by two coupling protocols is shown to result in vesicle aggregation. The degree of aggregation is directly related to the levels of protein conjugated to the liposomes. In an attempt to develop a method of generating stable, homogeneously sized protein-conjugated vesicles, highly aggregated liposome-protein conjugates were extruded through filters of defined pore size distributions, with no loss of protein binding. The extruded samples are relatively stable with respect to size and are easily prepared for various protein to lipid ratios. Liposome size has been shown to be a major factor in determining the in vivo blood circulation times of liposomes. A corresponding, significant enhancement in the blood circulation lifetimes for extruded versus aggregated streptavidin-liposome conjugates is observed. Furthermore, the stability of streptavidin-liposome conjugates in vivo was shown by the binding of biotin to liposomes isolated from plasma 1 and 4 h post-injection. In conclusion, extrusion of the aggregated systems obtained on coupling proteins to liposomes provides a convenient and general method for generating homogeneously sized protein-liposome conjugates. PMID- 2207122 TI - Soybean phosphatidylcholine vesicles containing plant sterols: a fluorescence anisotropy study. AB - The typical plant sterols (sitosterol, stigmasterol and campesterol) were compared with respect to their ability to regulate membrane fluidity of soybean phosphatidylcholine (PC) vesicles. Fluidity changes were monitored by the steady state fluorescence anisotropy with 1,6-diphenyl-1,3,5-hexatriene as a probe and assigned to a measure of the acyl chain orientational order. Sitosterol and campesterol appear to be the most suitable sterols in ordering the acyl chains of soybean lecithin bilayers, even more efficient than cholesterol, the standard of reference for sterol effects on membranes, suggesting that they play a significant role in the regulation of plant membrane properties. Stigmasterol is shown to be much less active. Cycloartenol, a biosynthetic precursor of plant sterols, increases the acyl chain order with the same efficiency as cholesterol. We also investigated the effects of two unusual sterols, 24-methylpollinastanol and 14 alpha,24-dimethylcholest-8-en-3 beta-ol, which were shown to accumulate in plants treated with fungicides belonging to two important classes, N-substituted morpholines and triazoles, respectively. These two sterols exhibit a behavior very similar to that of stigmasterol. The results are discussed in terms of sterol effects on the molecular packing of soybean PC bilayers. PMID- 2207123 TI - Increased oxidation of p-nitrophenol and aniline by intact hepatocytes isolated from pyrazole-treated rats. AB - Induction of cytochrome P-450 IIE1 by pyrazole has been shown in a variety of studies with isolated microsomes or reconstituted systems containing the purified P-450 isozyme. Experiments were conducted to document induction by pyrazole in intact hepatocytes by studying the oxidation of p-nitrophenol to 4-nitrocatechol or of aniline to p-aminophenol. Hepatocytes prepared from rats treated with pyrazole for 2 days oxidized p-nitrophenol or aniline at rates which were 3- to 4 fold higher than saline controls. To observe maximal induction in hepatocytes, it was necessary to add metabolic substrates such as pyruvate, sorbitol or xylitol, which suggests that availability of the NADPH cofactor may be rate-limiting in the hepatocytes from the pyrazole-treated rats. Carbon monoxide inhibited the oxidation of p-nitrophenol and aniline by hepatocytes from the pyrazole-treated rats and controls, demonstrating the requirement for cytochrome P-450. The oxidation of both substrates by the hepatocyte preparations was inhibited by a variety of agents that interact with and are effective substrates for oxidation by P-450 IIE1 such as ethanol, dimethylnitrosamine, pyrazole and 4 methylpyrazole. Microsomes isolated from pyrazole-treated rats oxidized aniline and p-nitrophenol at elevated rats compared to saline controls. These results indicate that induction by pyrazole of the oxidation of drugs which are effective substrates for P-450 IIE1 can be observed in intact hepatocytes. The extent of induction and many of the characteristics of aniline or p-nitrophenol oxidation observed with isolated microsomes from pyrazole-treated rats can also be found in the intact hepatocytes. PMID- 2207124 TI - Substrate specificity and inhibitor sensitivity of a trypanosomatid alkaline peptidase. AB - An alkaline peptidase of Trypanosoma cruzi and Crithidia fasciculata, previously shown to cleave on the carboxyl side of arginine and lysine residues, was examined for its ability to cleave various fluorogenic substrates and for its sensitive to peptidase inhibitors. The enzyme of both T. cruzi and C. fasciculata has a preference for cleavage of substrates with basic amino acids at the P2 as well as the P1 position of the peptide chain. Arginine and lysine are equally acceptable at P2, whereas the enzyme prefers arginine to lysine at P1. An influence of the P3 amino acid residue on substrate cleavability was also apparent. The peptidase was highly susceptible to inactivation by peptidylfluoromethanes, peptidyldiazomethanes and peptidylsulphonium salts that contained arginine or lysine at P1. Additionally, diisopropylfluorophosphate inhibited the enzyme, whereas trans-epoxysuccinylleucylamido(4-guanidino)butane and iodoacetic acid were relatively weak inhibitors. Various reversible inhibitors of the enzyme were also examined. Inhibition by members of the primary aliphatic amine series, methylamine to n-heptylamine, showed a peak of inhibition at n-butylamine, which most closely resembles the lysine side chain. Agmatine, which resembles the arginine side chain, also strongly inhibited the peptidase. The kinetics of inhibition by these basic compounds were of the competitive type. Pentamidine and hirudonin, which resemble two arginine side chains joined together, were more effective inhibitors of the trypanosomatid peptidase than bases resembling only one arginine or lysine side chain. PMID- 2207125 TI - Hydrogen peroxide production by monoamine oxidase in isolated rat-brain mitochondria: its effect on glutathione levels and Ca2+ efflux. AB - H2O2 production and accumulation during incubation of isolated rat-brain mitochondria with substrates of monoamine oxidase A and B were investigated. All substrates gave rise to an accumulation of H2O2 which was inhibited by malate + pyruvate or isocitrate, consistent with a need for mitochondrial NADPH to maintain glutathione in the reduced state. However, in the absence of these additions the level of reduced glutathione decreased only by about 30%, indicating that only a fraction of the mitochondrial glutathione pool was accessible to the glutathione peroxidase and glutathione reductase activities responsible for the continuous removal of H2O2 generated by monoamine oxidase. The H2O2 accumulation was also inhibited by externally added reduced glutathione or NADPH but not NADH. External NADPH was oxidized by added oxidized glutathione but not alpha-ketoglutarate + NH4+. These results suggest that the removal of H2O2 generated by monoamine oxidase proceeds by way of special fractions of glutathione peroxidase and glutathione reductase that are located in the intermembrane space of mitochondria in such a way that they can react with both intra- and extra-mitochondrial glutathione and NADPH, possibly at the contact sites between the inner and outer mitochondrial membranes. Evidence is also presented that H2O2 generated by monoamine oxidase enhances Ca2+ release from mitochondria and may thus function as a regulator of mitochondrial Ca2+ efflux. PMID- 2207126 TI - Isolation and characterization of a transferrin binding protein from rat plasma. AB - A transferrin binding protein was isolated from normal rat placenta and from iron deficient rat plasma using a human transferrin affinity column. The yield of the isolated pure protein from iron-deficient rat plasma was about 0.5 micrograms/ml plasma. The major protein had a molecular mass of 85 kDa and contained carbohydrate. Reduction with mercaptoethanol did not change the molecular mass of the plasma transferrin binding protein whereas the native placental transferrin receptor of 180 kDa was reduced to 90 kDa. The transferrin binding protein reacted with both monoclonal and polyclonal antibodies raised against rat transferrin receptor. Immunoblotting of both normal and iron deficient rat plasma showed that the transferrin binding protein had a molecular mass of 85 kDa. In vitro digestion of purified rat placental transferrin receptor and red blood cells with trypsin provided an identical peptide profile, suggesting that the transferrin binding protein in rat plasma is derived from proteolysis of the extracellular portion of the transferrin receptor of the erythroid tissues. PMID- 2207127 TI - A pulse radiolysis investigation of the oxidation of methoxylated metabolites of indolic melanin precursors. AB - The rate constants associated with the series of successive transient absorptions initiated by one-electron oxidation of 6-hydroxy-5-methoxyindole (6H5MI) and its isomer 5-hydroxy-6-methoxyindole (5H6MI) have been studied by pulse radiolysis. These close analogues of 5,6-dihydroxyindole (DHI) are metabolites of the oxidative melanogenic pathway. The species initially produced from N3. oxidation of both methoxyindoles at pH 7.2-7.4 are assigned as the corresponding semiquinones. That from 6H5MI shows peak at 500, 370 and 330 nm, very close to those of the semiquinone of DHI, whereas the semiquinone of 5H6MI shows no absorption at 500 nm but bands at 420 and 340 nm. These spectral differences are attributed to marked changes in the degrees of electron delocalisation for the two types of radical, both rings of the indole being involved for the 6H5MI radical but only the benzenoid moiety for the 5H6MI radical. In both cases, the radicals decayed, probably by disproportionation, into products which absorbed in the 400-420 nm region. For 6H5MI, the subsequent decay in this region was best fitted by two consecutive first-order processes which were both strongly base catalysed. The first of these processes is assigned to partial decay via deprotonation of the corresponding quinonoid cation to form an equilibrium mixture of this cation and the corresponding quinone methide. The second process is assigned to reaction of the quinone methide with water yielding hydroxylated product(s) which may subsequently react with remaining quinonoid cation or quinone methide to give dimeric product(s) with broad absorption centreing in the 550 nm region detected 0.5 s after the pulse. For 5H6MI, the decay at 430 nm fitted a single first-order process, which was weakly base-catalysed. This process is attributed to deprotonation of the corresponding quinonoid cation to the corresponding quinone imine absorbing below 350 nm, which was stable for at least tens of seconds. The current experiments suggest that our previous analogues observations (Lambert et al. (1989) Biochim. Biophys. Acta 993, 12-20) on the oxidation of the melanogenic precursors DHI and 5,6-dihydroxyindole-2 carboxylic acid (DHICA) may be interpreted, as with 6H5MI, in terms of the corresponding indolequinones decaying into equilibrium mixtures of quinone, quinone imine and quinone methide. These decay via reaction of the methide with water generating hydroxylated species which proceed to give the coloured product(s) absorbing in the 550 nm region. PMID- 2207128 TI - Mathematical modelling of the purine metabolism of the rat liver. AB - The regulation of the purine metabolism of the rat liver is studied on the basis of a mathematical model which comprises rate laws and kinetic constants of all physiologically relevant reactions. The computed stationary and time-dependent concentrations are in good accordance with experimental data obtained in the ischaemic rat liver and in isolated hepatocytes. In particular, model-based simulations of the adenine nucleotide metabolism have been performed for situations where ATP-deficient states of the cell (hypoxia, anoxia or ischaemia) of various length are followed by onset of ATP production (reoxygenation). These simulations confirm the experimentally observed incomplete recovery of ATP and of the total pool of adenine nucleotides within a few hours of reoxygenation after long-term ATP depletion. Therefore, it can be concluded that this phenomenon is an intrinsic regulatory property of the purine metabolism and not necessarily due to some irreversible changes in the activity of the enzymes involved. PMID- 2207129 TI - Stopped-flow investigation of antioxidant activity of estrogens in solution. AB - A kinetic study of the reaction between estrogens (female hormone) and substituted phenoxyl radical has been performed, as a model for the reactions of estrogens with lipid peroxyl radical in biological systems. The rates of reaction of estrogens (estrone 1, estradiol 2, 2-methoxyestrone 3, 3-methoxyestrone 4, and 2-hydroxyestrone 5) with substituted phenoxyl radical in benzene have been determined spectrophotometrically, using stopped-flow technique. The second-order rate constants, k2, obtained are 84 M-1.s-1 for 1, 138 M-1.s-1 for 2, 520 M-1.s-1 for 3, less than 10(-4) M-1.s-1 for 4, and 2.6 X 10(5) M-1.s-1 for 5 at 25.0 degrees C. 2-Hydroxyestrone 5 was found to be 2.9-times more active than alpha tocopherol, which has the highest antioxidant activity among natural tocopherols. The order of magnitude of k2 value (1 less than 2 less than 3 less than alpha-Toc less than 5) is in agreement with that of in vitro tests of their antioxidant activities, as measured by the inhibition of lipid peroxidation. Further, similar measurements have been performed for the reaction between the above estrogens 1-5 and tocopheroxyl 6 in benzene solution. It was found that the estrogens having an OH group at the aromatic ring have an ability to regenerate the tocopheroxyl 6 to tocopherol. Especially, the 2-hydroxyestrone 5 showed about three orders of magnitude higher reactivity than ascorbic acid. PMID- 2207130 TI - Procoagulant activity of collagen. Effect of difference in type and structure of collagen. AB - Procoagulant activities of different types and structures of collagen were examined. Collagens used were types I (including its methylated and succinylated forms), II, III, IV and V. Each collagen was coated on an inner surface of a glass tube. The change of fluidity during coagulation of blood in the tube was measured by means of a new rheological technique. For monomeric collagen, the procoagulant activity of the succinylated form (negatively charged) was higher than that of the methylated form (positively charged). The procoagulant activity of type IV (dry) was lower than that of other types of collagen. For fibrillar collagens, the initiation of coagulation for type V (non-banded) was fairly delayed compared to those for types I, II and III (banded). An increase in water content in both monomeric and fibrillar forms promoted procoagulant activity. For most of the collagen forms, the addition of factor XII inhibitor (Polybrene) to blood brought about a remarkable delay of the initiation of coagulation, suggesting that the activation of factor XII on the collagen surface is one of main factors governing procoagulant activity. In addition, our data suggest that large numbers of adherent platelets to the collagen surface promote activation of the intrinsic coagulation system. PMID- 2207131 TI - Study of proteolytic activities released by incubation of trypanosomes (Trypanosoma brucei brucei) in pH 5.5 and pH 7.0 phosphate/glucose buffers. AB - Proteolytic activities released by overnight incubation of Antwerpeen Trypanozoon antigenic type (AnTat) 1.1 trypanosomes at 4 degrees C in pH 5.5 and pH 7.0 phosphate/glucose buffers were analyzed in the supernatants obtained after centrifugation of the parasite suspensions. The assays used the fluorogenic substrates N-alpha-benzyloxycarbonyl-L-phenyl-alanyl-L-arginine-7-amido-4- methylcoumarin (Z-Phe-Arg-NMec) and N-alpha-benzyloxycarbonyl-L-arginyl-L arginine-7- amido-4-methylcoumarin (Z-Arg-Arg-NMec) at two different pHs (6.0 and 8.3). Z-Phe-Arg-NMec hydrolysis was inhibited by 2 microM L-trans epoxysuccinyllencylamido(4-guanidino)butane (E-64) to a greater extent in the pH 7.0 supernatant than in the pH 5.5 supernatant. Z-Arg-Arg-NMec hydrolysis by the two supernatants was not significantly inhibited by 2 microM E-64. At pH 8.3 this activity was increased more than 2-fold by the addition of dithiothreitol. The hydrolysis activities were analyzed in collected eluates after fractionation of the supernatants by gel permeation high-performance liquid chromatography. Z-Phe Arg-NMec hydrolytic activity inhibited by 2 microM E-64 was maximal at a retention time of 33 min (approx. Mr 30,000). In addition, a hydrolytic activity against the substrates Z-Phe-Arg-NMec and Z-Arg-Arg-NMec gave a peak showing a maximum at a retention time of 29 min (approx. Mr 70,000). PMID- 2207132 TI - Measurement of intracellular magnesium in a vascular smooth muscle cell line using a fluorescent probe. AB - Until recently, direct measurement of intracellular free magnesium has been complex and difficult. However, fluorescent probes are now available, based on the same principle as well-established probes for free calcium. Using one such probe, mag-fura-2, we have estimated basal intracellular magnesium concentrations in the A7r5 rat vascular smooth muscle cell line. This level was unaffected by numerous pharmacological manipulations, including agonist stimulation and depolarisation. The possible implications of these findings are discussed. PMID- 2207133 TI - Mechanism and control of translation. Papers presented at the EMBO/FEBS/IUB advanced course. 12-17 May 1990. Noordwijkerhout, The Netherlands. PMID- 2207134 TI - Crystals of complexes mimicking protein biosynthesis are suitable for crystallographic studies. AB - A complex of 70S ribosomes from Thermus thermophilus together with an average of 1.5-1.8 equivalents of PhetRNA(Phe) and a short mRNA chain, composed of 35 +/- 5 uridines, was crystallized under the conditions used for the growth of crystals of isolated ribosomes from the same source. Considering the reproducibility of their growth, their internal order and their shape, the crystals of the complex are superior to those of isolated ribosomes. In accord with previous three dimensional reconstruction and modeling experiments, we conclude that the complex is less flexible and that an average population of complexes is more homogeneous than that of isolated 70S ribosomes. The crystals of the complex diffract to higher than 15 A resolution and can be irradiated with synchrotron X-ray beam at cryo-temperatures for days without noticeable decay. Since the crystals of the complex are apparently isomorphous with these of the isolated 70S ribosomes (P4(1)2(1)2; a = b = 526; c = 315 A), they should provide tool for phasing as well as for locating the mRNA and tRNA binding sites. PMID- 2207135 TI - Complete nucleotide sequence of the group I RNA bacteriophage fr. AB - We report the complete nucleotide sequence of the group I RNA bacteriophage fr. The entire genome consists of 3575 nucleotides, six nucleotides more than the only other sequenced group I representative, MS2. The greatest divergence between these phages occurs in the 5' terminal region of the A gene, while the lysis replicase gene overlap, the coat gene and the central region of the replicase gene are highly conserved. Overall sequence homology between fr and MS2 is 77%. Here, we present a general comparison between the two phages. In the accompanying paper we use phylogenetic sequence comparison between MS2 and fr to deduce the secondary structure at the 3' untranslated region. PMID- 2207136 TI - Secondary structure at the 3' terminal region of RNA coliphages: comparison with tRNA. AB - Secondary structure models for the 3' non-coding region of the four groups of coliphage RNA are proposed based on comparative sequence analysis and on previously published data on the sensitivity of nucleotides in MS2 RNA to chemical modification and enzymes. We report the following observations. (1) In contrast to the coding regions, the structure at the 3' terminus is characterized by stable regular helices. We note the occurrence of the loop sequences 5'-GUUCGC and 5'-CGAAAG, that are reported to confer exceptional stability to stem structures. These features are probably present to promote the segregation of mother and daughter strands during replication. (2) Comparison of homologous helices indicates that only those base pair substitutions are allowed that maintain the thermodynamic stability. (3) We have compared the structure of phage RNA with tRNA. Overall similarity is low, but one common element may exist. It is a quasi-continuous helix of 12 basepairs that could be the equivalent of the 12 basepair long coaxially stacked helix, formed by the T psi C arm and the aminoacyl acceptor arm in tRNA. As in tRNA, this structure element starts after the fourth nucleotide from the 3' end. (4) Phage RNA contains a large variable region of about 35 nucleotides bulging out from the quasi-continuous helix. We speculate that the variable loop in present-day tRNA could be the remnant of the variable region found in phage RNA. The variable region contains overlapping binding sites for the replicase enzyme and the maturation protein. This common binding site may serve as a switch from replication to packaging. PMID- 2207137 TI - Transition of the mRNA sequence downstream from the initiation codon into a single-stranded conformation is strongly promoted by binding of the initiator tRNA. AB - Using an RNA footprinting technique, accessible sites on the mRNA initiation region bound to the ribosome have been determined. Chemical probing experiments have been done both in the presence and absence of the initiator tRNA with dimethyl sulfate, kethoxal and carbodiimide as reagent probes. As an mRNA, a mini mRNA containing the initiation region of bacteriophage lambda gene cro has been used. This region is characterized by a long single-stranded Shine-Dalgarno (SD) sequence followed by two hairpin structures of which the first one comprises in its loop the initiation codon. As compared to a free mRNA, the only nucleotides additionally protected in the binary mRNA-ribosome complex have been those which belong to the S-D sequence and the initiation codon. The protection of other nucleotides has not changed. Addition of the initiator RNA results in the modification of nucleotides in the stems of the downstream hairpin structures of the initiation region. This reflects their transition into a single-stranded conformation promoted by tRNA. A possible implication of these findings for the decoding process is discussed. PMID- 2207138 TI - Is there a special function for U.G basepairs in ribosomal RNA? AB - U.G basepairs are well-established elements of RNA structure. The geometry of this pair is different, however, from classical Watson-Crick basepairs. This leads to an unusual stacking of the basepair: overlap with the basepair at the 5' side of the U (and the 3' side of the G) is strong (stacked) while it is weak with the basepair on the other side (destacked). The closure of an RNA helix by a U.G pair will be energetically unfavourable when the U residue occupies the 5' end. In transfer RNA there is a strong selection against a 'destacked' U.G pair at helix ends. In the 16S rRNA model of Escherichia coli there are 72 U.G pairs of which 36 or 22 occupy a helix end, depending on how such an end is defined. There is a slight preference for 'stacked' U.G's in these positions. It is remarkable, however, that of 13 very conserved U.G pairs in the 16S (-like) rRNA, 7 occur at helix ends and that 5 of these have the 'destacked' configuration. It is suggested that these pairs, if they exist at all in a hydrogen-bounded form, are stabilized by co-axial stacking with other helices or by interaction with a protein. PMID- 2207139 TI - cis-acting sequences involved in the translational control of GCN4 expression. AB - Four short upstream open reading frames (uORFs) in the mRNA leader are required for the translational control of GCN4 expression in response to amino acid availability. Data are reviewed demonstrating that the fourth (3' proximal) uORF is sufficient to establish the repressed levels of GCN4 expression, while the first uORF functions as a positive regulatory element under starvation conditions to stimulate GCN4 translation. Furthermore, positive and negative trans-acting regulatory factors, the activities of which appear to be modulated according to amino acid availability, exert their effects on GCN4 expression through the uORFs. Direct comparison of the uORFs indicates that there are important nucleotide sequence differences between uORF1 and 4, and that these are located primarily around the termination codons of these elements. Recent findings suggest that the sequences that mediate repression of GCN4 expression are complex, but can be overcome under starvation conditions by ribosomes that have previously translated uORF1. PMID- 2207140 TI - A fluorescence study of the interaction of protein synthesis initiation factors 4A, 4E, and 4F with mRNA and oligonucleotide analogs. AB - The initial interaction of mRNA with the protein synthesis machinery presumably involves recognition of the 5'-cap (m7GpppN), although it is not clear at the present time whether this recognition is by eIF-4E or eIF-4F. This process has been studied by direct fluorescence titration experiments. The equilibrium constants for the formation of the binary protein: m7GpppG, protein:mRNA, and protein:protein complexes as well as the ternary mRNA:eIF-4E:eIF-4A complexes were measured. These studies show, for the first time, direct evidence for an eIF 4A:eIF-4E interaction. In contrast to earlier studies, we show that the affinity of eIF-4E and eIF-4F for globin mRNA is similar. Furthermore, the relative affinities of mRNA analogs (capped oligonucleotides) for these initiation factors indicate that the cap is the predominant feature recognized for binding, but other features also contribute to the eIF-4E:mRNA interaction. PMID- 2207141 TI - Search of essential parameters for the aminoacylation of viral tRNA-like molecules. Comparison with canonical transfer RNAs. AB - Comparative structural and functional results on the valine and tyrosine accepting tRNA-like molecules from turnip yellow mosaic virus (TYMV) and brome mosaic virus (BMV), and the corresponding cognate yeast tRNAs are presented. Novel experiments on TYMV RNA include design of variant genes of the tRNA-like domain and their transcription in vitro by T7 RNA polymerase, analysis of their valylation catalyzed by yeast valyl-tRNA synthetase, and structural mapping with dimethyl sulfate and carbodiimide combined with graphical modelling. Particular emphasis is given to conformational effects affecting the valylation capacity of the TYMV tRNA-like molecule (e.g., the effect of the U43----C43 mutation). The contacts of the TYMV and BMV RNAs with valyl- and tyrosyl-tRNA synthetases are compared with the positions in the molecules affecting their aminoacylation capacities. Finally, the involvement of the putative valine and tyrosine anticodons in the tRNA-like valylation and tyrosylation reactions is discussed. While an anticodon-like sequence participates in the valine identity of TYMV RNA, this seems not to be the case for the tyrosine identity of BMV RNA despite the fact that the tyrosine anticodon has been shown to be involved in the tyrosylation of canonical tRNA. PMID- 2207143 TI - Aminoacylation of 3' terminal tRNA-like fragments of turnip yellow mosaic virus RNA: the influence of 5' nonviral sequences. AB - The present model of the L-shaped tRNA-like structure of turnip yellow mosaic virus (TYMV) RNA encompasses 82 nucleotides. A previous kinetic study on 3' terminal TYMV RNA fragments that contain the tRNA-like structure and a 5' nonviral GGGAGA sequence, suggested that viral sequences upstream of the tRNA like domain, i.e., upstream of nucleotide 82, increase the rate of aminoacylation (Dreher et al. (1988) Biochimie 70, 1719-1727). Here we report an increase in the aminoacylation rate when the number of nonviral nucleotides at the 5' end of TYMV RNA transcripts was reduced. The influence of these 5' proximal nonviral sequences on the conformation of the RNA molecule was investigated by structure mapping experiments. A structure that deviates from the tRNA-like structure was found in some of the transcripts. The formation of this alternative structure is dependent upon: (1) the nature and number of the nonviral nucleotides; (2) the number and secondary structure of viral nucleotides between the nonviral nucleotides and the tRNA-like domain. Footprinting experiments with valyl-tRNA synthetase from yeast suggest that the enzyme does not recognize the alternative structure. PMID- 2207142 TI - Site-specific mutation of the conserved m6(2)A m6(2)A residues of E. coli 16S ribosomal RNA. Effects on ribosome function and activity of the ksgA methyltransferase. AB - In vitro synthesis of mutant 16S RNA and reconstitution with ribosomal proteins into a mutant 30S ribosome was used to make all possible single base changes at the universally conserved A1518 and A1519 residues. All of the mutant RNAs could be assembled into a ribosomal subunit which sedimented at 30 S and did not lack any of the ribosomal proteins. A series of in vitro tests of protein synthesis ability showed that all of the mutants had some activity. The amount varied according to the assay and mutant, but was never less than 30% and was generally above 50%. Therefore, neither the conserved A1518 nor A1519 residues are essential for ribosome function. The mutant ribosomes could also be methylated by the ksgA methyltransferase to 70-120% of the expected amount. Thus, neither of the A residues is required for methylation of the other, ruling out any obligate order of methylation of A1518 and A1519. PMID- 2207144 TI - The extension of polyphenylalanine and polylysine peptides on Escherichia coli ribosomes. AB - Fluorescence techniques were used to examine aminoacyl-tRNA binding to Escherichia coli ribosomes and the subsequent extension of polyphenylalanine and polylysine nascent peptides. The results demonstrate that deacylated tRNA, an analogue of peptidyl-tRNA and puromycin (an analogue of aminoacyl-tRNA) can be bound simultaneously to the same ribosome. Moreover, the fluorescence properties of nascent polyphenylalanine and polylysine peptides with a fluorophore attached to their amino termini were determined and found to be quite different. This difference is reflected in the effects that erythromycin has in each case. PMID- 2207145 TI - Structural determination of the functional sites of E. coli elongation factor Tu. AB - Recently, we have made significant progress in solving the structure of a nicked form of elongation factor (EF)-Tu complexed with GDP. The structure has been refined to an R factor of 19.2% at 2.6 A resolution, so that most of the structure is clearly visible in the electron density map. Here we describe what is known about functional sites of EF-Tu in terms of the structure, which still lacks amino acids 40-60. PMID- 2207146 TI - Ternary complexes of Escherichia coli aminoacyl-tRNAs with the elongation factor Tu and GTP: thermodynamic and structural studies. AB - The interaction of 18 different Escherichia coli aminoacyl-tRNA species with elongation factor Tu and GTP has been measured by a fluorescence titration assay under equilibrium conditions. The dissociation constants range from 1.9 +/- 0.2.10(-10) M up to 1020 +/- 250.10(-10) M depending on the nucleotide sequence, secondary structure and the chemical composition of the aminoacyl residue of the particular aminoacyl-tRNA. The 'aminoacyl domain' of tRNA consisting of the single stranded, four-nucleotide-long 3'-terminus, aminoacyl stem of seven base pairs, T-stem and T-loop contains all elements necessary for binding EF-Tu.GTP. The efficiency of aminoacyl-tRNA interaction with EF-Tu.GTP is modulated by the sequence of this 'aminoacyl domain' and by natural modification of its nucleotide residues. An oligoribonucleotide resembling the aminoacyl stem of E.coli tRNA(Ala) and consisting of a four-membered 3'-end, a stem of seven base-pairs and a loop of six nucleotides was prepared by total chemical synthesis on a polymer support. It can be enzymatically aminoacylated by alanine but does not bind in its aminoacylated form to EF-Tu.GTP. PMID- 2207147 TI - The interaction between aminoacyl-tRNA and the mutant elongation factors Tu AR and B0. AB - The binding of Tyr-[AEDANS-s2C]tRNA(Tyr) (Tyr-tRNA(Tyr) modified at the penultimate cytidine residue with a thio group at position 2 of the pyrimidine ring, to which an N-(acetylaminoethyl)-5-naphthylamine-1-sulfonic acid fluorescence group is attached) to mutant elongation factor (EF)-Tu species from E. coli, EF-TuAR (Ala-375----Thr) and EF-TuBO (Gly-222----Asp), both complexed to GTP, was investigated in absence of kirromycin by measuring the change in fluorescence of the modified tRNA induced by complex formation. The calculated dissociation constant in the case of EF-TuAR is about 4 nM and in the case of EF TuB0, about 1 nM. These values are higher than that of wild-type EF-Tu, which was 0.24 nM measured with the same system. The affinity between either EF TuB0.kirromycin.GDP or EF-TuB0.kirromycin.GTP on the one hand, and a mixture of aminoacyl-tRNAs on the other, was measured with zone-interference gel electrophoresis. The dissociation constants are 20 microM and 7 microM, respectively, a factor of about two higher than in the case of wild-type EF Tu.kirromycin. These findings provide a clue for the observed increase in translational errors in strains carrying the mutations. Furthermore, the experiments with EF-TuB0.kirromycin deepen our understanding of the effects of the B0 mutation on the kirromycin phenotype of the mutant cells concerned. PMID- 2207148 TI - Characterization of protein synthesis factors from rabbit reticulocytes. AB - As part of our efforts to characterize eukaryotic translation factors, we have sequenced a number of them chemically and inferred sequences from cDNA clones. To our surprise, there appears to be extensive identity of amino acid sequence in most factors characterized to date in that within mammalian species, usually greater than 99% identity is observed. Extreme examples are rabbit EF-1 alpha which is 100% identical to human EF-1 alpha and rabbit eIF-4AI and eIF-4AII which are 100% identical to mouse eIF-4AI and eIF-4AII for those amino acids sequenced (398/406 and 156/407, respectively). An extended analysis has been made of EF-1 alpha which in rabbit has three different post-translational modifications, dimethyllysine, trimethyllysine and glycerylphosphorylethanolamine. A comparison of the primary structure of EF-1 alpha to E. coli EF-Tu indicates an overall sequence identity of 33%. However, within the amino terminal 180 amino acids (the GTP-binding domain), there are found regions of much greater identity (50/85 = 59%). PMID- 2207149 TI - Elongation factor 1 beta of artemia: localization of functional sites and homology to elongation factor 1 delta. AB - Elongation factor (EF)-1 beta, a 26 kDa protein, is the eukaryotic equivalent of bacterial EF-Ts, the nucleotide exchange factor in protein synthesis. EF-1 beta catalyzes the exchange of guanine nucleotides bound to EF-1 alpha; the latter protein is the eukaryotic equivalent of bacterial EF-Tu. Limited proteolytic cleavage studies on EF-1 beta lead to the following picture: the protein is composed of two domains, an aminoterminal and a carboxyterminal domain, connected to each other by a stretch of hydrophilic, charged amino acids situated in the middle of the molecule. The carboxyterminal domain supplies the catalytic site for the nucleotide exchange reaction, whereas the aminoterminal domain interacts with EF-1 gamma, the third component of elongation factor 1. The regulatory, serine phosphate residue, Ser-89, localized in the hydrophilic stretch of EF-1 beta, does not appear to be necessary for the basic exchange reaction. The fourth component of the high molecular weight elongation factor complex (EF-1H), named EF-1 delta or 28 K protein, is homologous to EF-1 beta and contains regions very similar to the carboxyterminal part. EF-1 delta was found to be active in the nucleotide exchange reaction. PMID- 2207150 TI - Growth rate dependence of global amino acid composition. AB - The global amino acid composition of bacteria growing in different media has been studied. The data reveal significant changes in the amino acid composition in the growth rate range between 0.5 and 2.1 doublings per hour at 37 degrees C. The changes are consistent with a progressive simplification of the protein population and mRNA pools as the growth rates increase. PMID- 2207151 TI - The influence of the concentrations of elongation factors and tRNAs on the dynamics and accuracy of protein biosynthesis. AB - Computer simulations of the elongation cycle of bacterial protein biosynthesis demonstrate that the accuracy of protein biosynthesis cannot be explained by a mechanism which involves only an initial selection and a proofreading reaction. It is suggested that only a combination of initial selection, proofreading and a retardation of non-cognate flows at the level of the EF-Tu-catalyzed GTPase reaction and the peptidyl transfer can guarantee sufficient accuracy at reasonable costs. According to this view the ribosome functions as an allosteric enzyme which, in both its affinity and enzymatic activity, responds optimally only to the cognate substrate. Detailed calculations show, furthermore, that increasing the concentration of EF-G and EF-Ts above the level prevailing in vivo only slightly increases the rate of elongation. In contrast, increasing the concentration of EF-Tu over aminoacyl-tRNA (aa-tRNA) leads to a sharp decline in the rate of elongation. While varying the concentration of EF-G has no effect on the accuracy of protein synthesis, excess of EF-Tu over aminoacyl-tRNA leads to a large increase in accuracy. These results suggest a mechanism by which the accuracy of protein biosynthesis is preserved during amino acid starvation. PMID- 2207152 TI - Third position base changes in codons 5' and 3' adjacent UGA codons affect UGA suppression in vivo. AB - The base sequence around nonsense codons affects the efficiency of nonsense codon suppression. Published data, comparing different nonsense sites in a mRNA, implicate the two bases downstream of the nonsense codon as major determinants of suppression efficiency. However, the results we report here indicate that the nature of the contiguous upstream codon can also affect nonsense suppression, as can the third (wobble) base of the contiguous downstream codon. These conclusions are drawn from experiments in which the two Ser codons UCU233 and UCG235 in a nonsense mutant form (UGA234) of the trpA gene in Escherichia coli have been replaced with other Ser codons by site-directed mutagenesis. Suppression of these trpA mutants has been studied in the presence of a UGA nonsense suppressor derived from glyT. We speculate that the non-site-specific effects of the two adjacent downstream bases may be largely at the level of the termination process, whereas more site-specific or codon-specific effects may operate primarily on the activity of the suppressor tRNA. PMID- 2207153 TI - Role of tRNA modification in translational fidelity. AB - In transfer RNA many different modified nucleosides are found, especially in the anticodon region. In this region, pseudouridine (psi) is found in positions 38, 39 or 40 in a subset of tRNA species, 2-methylthio-6-hydroxyisopentenyladenosine (ms2io6A) is found in position 37 in tRNAs that read codons starting with U and 1 methylguanosine (m1G) is found in position 37 in tRNAs reading codons of the UCCNG type. We have used the mutants hisT, miaA and miaB and trmD, which are deficient in the biosynthesis of psi, ms2io6A, and m1G, respectively, to study the functional aspects of the respective modified nucleosides. We have shown: (1) Presence of psi improved the cellular growth rate, the polypeptide step-time, and the efficiency of an amber suppressor, but did not appreciably sense the codon context. (2) Presence of ms2io6A improved the cellular growth rate, the polypeptide step-time and the efficiency of several amber suppressor tRNAs. It also had a profound effect on the codon context sensitivity of the tRNA. (3) Presence of m1G improved the cellular growth rate and the polypeptide steptime and also prevented the tRNA from shifting the reading frame. Thus, these three modified nucleosides present in the anticodon region have apparently different functions. PMID- 2207154 TI - Guanosine modifications in runoff transcripts of synthetic transfer RNA-Phe genes microinjected into Xenopus oocytes. AB - We have investigated whether unmodified yeast phenylalanine transfer RNA as well as one of its precursors containing an intron of nineteen nucleotides in the anticodon (pre-tRNA-Phe) can become substrates for selected tRNA modification enzymes present in a eukaryotic cell. This study was done by microinjecting into the cytoplasm of Xenopus laevis oocytes transcripts completely deprived of the naturally occurring modified nucleotides; these were obtained in vitro from appropriate synthetic genes under the control of bacteriophage T7 promoter. During the in vitro transcription, 32P labels were introduced with the guanosine triphosphate thus allowing easy detection of guanosine modifications in tRNA by two-dimensional chromatography after complete digestion into 5'-mononucleotides by nuclease P1. Results indicate that modifications occur on five guanosines (at positions 10, 26, 34, 37 and 46) in yeast tRNA-Phe and only on three guanosines (at 10, 26 and 46) in yeast precursor tRNA-Phe. These are the modifications expected from the known nucleotide sequences of naturally occurring Xenopus and yeast tRNA-Phe, i.e. N2-methyl-G10, N2,N2-dimethyl-G26, 2'-O-methyl-G34, N1 methyl-G37 or Y nucleoside-37 and N7-methyl-G46. The rates of modifications occurring in the two kinds of tRNA-Phe are faster in the intron-less tRNA-Phe than in the intron-containing tRNA-Phe. However quantitative modifications are only observed after as long as 75 h incubation in the oocytes. PMID- 2207155 TI - Effects of mutagenesis of C912 in the streptomycin binding region of Escherichia coli 16S ribosomal RNA. AB - Four different mutations were produced at position 912 of Escherichia coli 16S rRNA in the multicopy plasmid pKK3535. Cells transformed with the mutant plasmids were assayed for growth in steptomycin. The U912 mutant conferred low level streptomycin resistance as reported originally by Montandon and co-workers (EMBO J 1986; 5:3705-3708). The G912 mutant also gave low level resistance but, unlike U912, caused significant retardation in growth rate and tended to select for fast growing revertants. The A912 mutant was without effect on growth rate or streptomycin sensitivity, while deletion of C912 was lethal. Cells with U912 were selected for increased streptomycin resistance (MIC up to 160 micrograms/ml) and then cured of the plasmid. The cured cells retained a higher level of streptomycin resistance (MIC: 80 micrograms/ml) than the original wild type strain (MIC: 10 micrograms/ml), but sequencing by reverse transcriptase showed no evidence of U912 in the cellular 16S rRNA. Thus, recombination of the plasmid coded U912 mutation into host rrn operons was not the mechanism by which increased streptomycin resistance occurred. The plasmid with U912 was transformed into three different streptomycin-dependent strains to determine whether the rRNA mutation, which presumably alters streptomycin binding, was compatible with S12 mutations which require bound streptomycin in order to function properly. In one strain, no transformants could be isolated, indicating that the plasmid was lethal. The two other streptomycin-dependent strains were transformed, but ribosomes containing the mutant rRNA were non-functional. PMID- 2207156 TI - The role of EF-Tu and other translation components in determining translocation step size. AB - The two EF-Tu encoding genes, tufA and tufB, of Salmonella typhimurium have been sequenced. Nearly all the differences from their Escherichia coli counterparts are third position changes which do not alter the encoded amino acids. Unexpectedly, most of the changes in one Salmonella tuf gene are paralleled by changes in the other tuf gene perhaps due to gene repair despite the distance separating the genes. Three mutants which cause mis-framing, have their substitutions at codon 375. Explanations for mutants which cause mis-framing are considered and the mechanism of normal reading frame maintenance discussed. PMID- 2207157 TI - A mutation which modifies the activity of a translational suppressor in Aspergillus nidulans. AB - A third type of translational fidelity mutation has been induced in Aspergillus nidulans. The new mutation enhances growth, in suppressing conditions, of a strain containing suppressor suaC109 and antisuppressor asuD14 and is called aloB8 for its allosuppressor activity. Compared with the progenitor strain (asuD14, suaC109), ribosomes from the new mutant (aloB8, asuD14, suaC109) increase misincorporation of leucine in a poly(U)-dependent homologous cell-free assay. The misreading level is maintained by ribosomes after washing with 500 mM KCl and suggests an alteration in a ribosomal component or a tightly bound factor. Ribosomes from an aloB8, asu+, sua+ strain also misread to a higher level than those of the control strain despite the fact that, in vivo, this mutation alone has no known suppressor activity. Mg2+ ions have been used in vivo for the first time to classify translation mutants. PMID- 2207158 TI - Frameshifting at the internal stop codon within the mRNA for bacterial release factor-2 on eukaryotic ribosomes. AB - A translational frameshift is necessary in the synthesis of Escherichia coli release factor 2 (RF-2) to bypass an in-frame termination codon within the coding sequence. High-efficiency frameshifting around this codon can occur on eukaryotic ribosomes as well as prokaryotic ribosomes. This was determined from the relative efficiency of translation of RF-2 RNA compared with that for the other release factor RF-1, which lacks the in-frame premature stop codon. Since the termination product is unstable an absolute measure of the efficiency of frameshifting has not been possible. A gene fusion between trpE and RF-2 was carried out to give a stable termination product as well as the frameshift product, thereby allowing a direct determination of frameshifting efficiency. The extension of RF-2 RNA near its start codon with a fragment of the trpE gene, while still allowing high efficiency frameshifting on prokaryotic ribosomes, surprisingly gives a different estimate of frameshifting on the eukaryotic ribosomes than that obtained with RF 2 RNA alone. This paradox may be explained by long distance context effects on translation rates in the frameshift region created by the trpE sequences in the gene fusion, and may reflect that pausing and translation rate are fundamental factors in determining the efficiency of frameshifting. PMID- 2207159 TI - Potential binding sites of the trans-activator FIS are present upstream of all rRNA operons and of many but not all tRNA operons. AB - FIS, the Escherichia coli protein that stimulates the inversion of various DNA segments by binding to a recombinational enhancer, trans-activates a number of stable RNA operons and binds to the upstream activator sequence (UAS) of these operons (Nilsson et al. (1990) EMBO J. 9, 727). In a search for potential FIS binding sites we have compared UASs of other stable RNA operons with a consensus FIS-binding sequence, compiled by comparing recombinational enhancers. Such sites can thus be recognized upstream of all rRNA and 13 tRNA operons. Matching with the consensus sequence varied, suggesting that the affinity of FIS for the sites differed. Accordingly, FIS binding to an upstream sequence of the metY(nusA) operon was found to be weaker than that to the UAS of the thrU(tufB) operon. No FIS binding sites were found upstream three tRNA operons. PMID- 2207160 TI - Regulatory elements downstream of the promoter of an rRNA gene of E. coli. AB - Previously we have shown that plasmid constructs carrying a reporter gene fused to the P2 promoter of the E. coli rrnB gene exhibited a strange two-phase kinetics of expression depending on the physiological conditions of the cell if a short DNA region downstream of the promoter was present between the promoter and the reporter gene (Lukacsovich et al. (1987) J. Bacteriol. 169, 272-277). Insertion of a synthetic oligonucleotide corresponding to the first half of this region into constructs where the reporter directly follows the promoter, leads to a complete block of expression in vivo, while in vitro--in a purified system- transcription is not inhibited. Band-shift experiments indicate that the putative regulatory region downstream of the promoter specifically binds protein(s) present in total bacterial extracts. PMID- 2207161 TI - Mapping of two promoters for elongation factor Tu within the structural gene for elongation factor G. AB - The str operon of Escherichia coli contains the genes for ribosomal proteins S7 and S12 as well as elongation factors G and Tu (EF-G, EF-Tu). We have previously reported that there is a secondary promoter for expression of EF-Tu mapping within the upstream fus gene encoding EF-G (Zengel, J.M. and Lindahl, L. (1982) Mol. Gen. Genet. 185, 487-492) and have identified several potential promoter sequences within fus (Zengel, J.M., Archer, R.H. and Lindahl, L. (1984) Nucleic Acids Res. 12, 2181-2192). We have now further characterized this promoter activity. Measurements of transcription rates from various regions of the str operon in cells carrying the fus gene and the beginning of the tufA gene on a high copy number plasmid confirmed that transcription was initiated within a 600 bp EcoRI fragment in the distal portion of the fus gene. Furthermore, T1 nuclease mapping studies identified two 5' ends within this region, one about 400 bases upstream of tufA, the other about 270 bases upstream, suggesting that there are two tufA promoters within the fus gene. Both of these promoters are active in the intact chromosomal str operon. PMID- 2207162 TI - Translational control of ribosomal protein S15. AB - The expression of ribosomal protein S15 is shown to be translationally and negatively autocontrolled using a fusion within a reporter gene. Isolation and characterization of several deregulated mutants indicate that the regulatory site (the translational operator site) overlaps the ribosome loading site of the S15 messenger. In this region, three domains, each exhibiting a stem-loop structure, were determined using chemical and enzymatic probes. The most downstream hairpin carries the Shine-Dalgarno sequence and the initiation codon. Genetic and structural data derived from mutants constructed by site-directed mutagenesis show that the operator is a dynamic structure, two domains of which can form a pseudoknot. Binding of S15 to these two domains suggests that the pseudoknot could be stabilized by S15. A model is presented in which two alternative structures would explain the molecular basis of the S15 autocontrol. PMID- 2207163 TI - Transcriptional organization of the S10, spc and alpha operons of Escherichia coli. AB - We have investigated the transcription patterns at the inter-operon regions between the S10 and spc, and spc and alpha ribosomal protein operons of Escherichia coli. Newly synthesized transcripts were characterized by RNase T1 protection experiments, and accumulated transcripts were mapped with S1 nuclease. With both techniques we found that about 75% of the RNA polymerases transcribing the S10 operon terminated at the position of a typical rho-independent terminator. In contrast, most or all RNA polymerases transcribing the spc operon continued into the alpha operon. Nevertheless, we observed that about 30% of the transcripts of the alpha operon were initiated at the alpha operon promoter. PMID- 2207164 TI - Dissection of the 16S rRNA binding site for ribosomal protein S4. AB - The ribosomal protein S4 from Escherichia coli is essential for initiation of assembly of 30S ribosomal subunits. We have undertaken the identification of specific features required in the 16S rRNA for S4 recognition by synthesizing mutants bearing deletions within a 460 nucleotide region which contains the minimum S4 binding site. We made a set of large nested deletions in a subdomain of the molecule, as well as individual deletions of nine hairpins, and used a nitrocellulose filter binding assay to calculate association constants. Some small hairpins can be eliminated with only minor effects on S4 recognition, while three hairpins scattered throughout the domain (76-90, 376-389 and 456-476) are essential for specific interaction. The loop sequence of hairpin 456-476 is important for S4 binding, and may be directly recognized by the protein. Some of the essential features are in phylogenetically variable regions; consistent with this, Mycoplasma capricolum rRNA is only weakly recognized by S4, and no specific binding to Xenopus laevis rRNA can be detected. PMID- 2207165 TI - The translational regulation of threonyl-tRNA synthetase. Functional relationship between the enzyme, the cognate tRNA and the ribosome. AB - The E. coli threonyl-tRNA synthetase gene is negatively autoregulated at the translational level by a direct binding of the enzyme to the leader region of the thrS mRNA. This region folds in four well-defined domains. The enzyme binds to the leader at two major sites: the first is a stem-loop structure located in domain II upstream of the translational initiation site (domain I) which shares structural analogies with the anticodon arm of several tRNA(Thr) isoacceptors. The second site corresponds to a stable stem-loop structure located in domain IV. Both sites are separated by a large unpaired region (domain III). In vivo and in vitro experiments show that the structural integrity of both sites is required for the regulatory process. The binding of the enzyme to its mRNA target site represses its translation by preventing the ribosome from binding to its attachment site. tRNA(Thr) suppresses this inhibitory effect by displacing the mRNA from the enzyme at both the upstream stem-loop structure and the tRNA-like anticodon arm. PMID- 2207166 TI - Multifunctional DNA-binding proteins mediate concerted transcription activation of yeast ribosomal protein genes. AB - Transcription activation of ribosomal protein genes (rp genes) in yeast is mediated through two different abundant transacting proteins, RAP1 and ABF1. These factors are multifunctional proteins playing a part in diverse cellular processes, all related to cellular growth. PMID- 2207167 TI - Probing tRNA binding sites on the Escherichia coli 30 S ribosomal subunit with photoreactive analogs of the anticodon arm. AB - Two analogs of the anticodon arm of yeast tRNAPhe (residues 28-43), in which G43 was replaced by the photoreactive nucleosides 2-azidoadenosine and 8 azidoadenosine, have been used to create 'zero-length' cross-links to ribosomal components at the peptidyl-tRNA binding site (P site) of 30 S subunits from the Escherichia coli ribosome. To prepare the analogs, 2-azidoadenosine and 8 azidoadenosine bisphosphates were first ligated to the 3' end of the anticodon containing dodecanucleotide ACmUGmAAYA psi m5CUG from yeast tRNAPhe. The trinucleotide CAG was then joined to the 5' end of the resulting tridecanucleotide in a subsequent ligation. Both analogs bound to poly(U) programmed 30 S subunits with affinities similar to that of the unmodified anticodon arm from yeast tRNAPhe. Irradiation of noncovalent complexes containing the photolabile analogs, poly(U) and 30 S ribosomal subunits with 300 nm light led to the covalent attachment of the anticodon arms to proteins S13 and S19. Further analysis revealed that S13 accounted for about 80%, and S19 for about 20%, of the cross-linked material. Labeling of these two proteins with 'zero length' cross-linking probes provides useful information about the location and orientation of P site-bound tRNA on the ribosome and permits a test of recently proposed models of the three-dimensional structure of the 30 S subunit. PMID- 2207168 TI - The acidic ribosomal proteins as regulators of the eukaryotic ribosomal activity. AB - The acidic proteins, A-proteins, from the large ribosomal subunit of Saccharomyces cerevisiae grown under different conditions have been quantitatively estimated by ELISA tests using rabbit sera specific for these polypeptides. It has been found that the amount of A-protein present in the ribosome is not constant and depends on the metabolic state of the cell. Ribosomes from exponentially growing cultures have about 40% more of these proteins than those from stationary phase. Similarly, the particles forming part of the polysomes are enriched in A-proteins as compared with the free 80 S ribosomes. The cytoplasmic pool of A-protein is considerably high, containing as a whole as much protein as the total ribosome population. These results are compatible with an exchanging process of the acidic proteins during protein synthesis that can regulate the activity of the ribosome. On the other hand, cells inhibited with different metabolic inhibitors produce a very low yield of ribosomes that contain, however, a surprisingly high amount of acidic proteins while the cytoplasmic pool is considerably reduced, suggesting that under stress conditions the ribosome and the A-protein may aggregate, forming complex structures that are not recovered by the standard preparation methods. PMID- 2207169 TI - Evidence for an additional archaebacterial gene cluster in Halobacterium marismortui encoding ribosomal proteins HL46e and HL30. AB - A small and extremely basic ribosomal protein (HL46e) has been purified from Halobacterium marismortui using reversed-phase high-performance liquid chromatography (HPLC). The amino acid sequence of the protein was determined by automated N-terminal and internal sequence analysis. Comparison of this sequence with other ribosomal protein sequences from eubacteria, archaebacteria and eukaryotes revealed a strong homology to SL46e from Sulfolobus solfataricus, YeaL46 from yeast and RL39 from rat. No significant sequence similarly was found to any eubacterial ribosomal protein so far known. Using a specific oligonucleotide probe the HL46e gene was identified, cloned and the nucleotide sequence including the 5'- and 3'-flanking regions were analysed. The HL46e gene is followed by the gene coding for HL30. A putative halobacterial promoter sequence with the motive 'TTTAAA' has been localized 32 bp upstream of the HL46e gene and a putative terminator sequence localized downstream from the HL30 gene. An equivalent to this HL46e/HL30 operon is apparently not present in Escherichia coli. PMID- 2207170 TI - The primary structure of rat ribosomal proteins: the amino acid sequences of L27a and L28 and corrections in the sequences of S4 and S12. AB - The amino acid sequences of rat ribosomal proteins L27a and L28 were deduced from the sequences of nucleotides in recombinant cDNAs and confirmed from the NH2 terminal amino acid sequences of the proteins. L27a contains 147 amino acids (the NH2-terminal methionine is removed after translation of the mRNA) and has a molecular weight of 16 476. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 18-22 copies of the L27a gene. The mRNA for the protein is about 600 nucleotides in length. L27a is homologous to mouse L27a (there are 3 amino acid changes) and to yeast L29. Rat ribosomal protein L28 has 136 amino acids (its NH2-terminal methionine is also processed after translation) and has a molecular weight of 15 707. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 9 or 10 copies of the L28 gene. The mRNA for the protein is about 640 nucleotides in length. L28 contains a possible internal duplication of 9 residues. Corrections are recorded in the sequences reported before for rat ribosomal proteins S4 and S12. PMID- 2207171 TI - In vivo and in vitro analysis of structure-function relationships in ribosomal protein L25 from Saccharomyces cerevisiae. AB - We have developed a combination of in vivo and in vitro methods which allows us to determine the effect of practically every structural change, deletions as well as point mutations, on various biological functions of a ribosomal protein (r protein). We have used this approach to delineate the functional domains of r protein L25 from Saccharomyces cerevisiae. By analysis of the intracellular distribution of fusion proteins carrying various portions of L25 linked to Escherichia coli beta-galactosidase we traced the nuclear localization signal(s) of L25 to the region encompassing the N-terminal 61 amino acids of the protein. On the other hand, using in vitro prepared fragments of L25 we located the domain responsible for its specific binding to 26S rRNA to the region between amino acids 61 and 135. In order to be able to analyze the effect of mutations in L25 on ribosome biogenesis and function in vivo we constructed a mutant yeast strain in which the chromosomal L25 gene is placed under control of the inducible yeast GAL promoter. Since this strain is unable to grow on glucose as a carbon source the L25 gene must be essential for cell viability. Growth on glucose can be restored by introduction of a wild-type L25 gene on a plasmid, demonstrating that under these conditions the cells are dependent upon an extrachromosomally supplied copy of the gene. PMID- 2207172 TI - The three-dimensional structure and function of Escherichia coli ribosomal RNA, as studied by cross-linking techniques. AB - A large number of intra-RNA and RNA-protein cross-link sites have been localized within the 23S RNA from E. coli 50 S ribosomal subunits. These sites, together with other data, are sufficient to constrain the secondary structure of the 23 S molecule into a compact three-dimensional shape. Some of the features of this structure are discussed, in particular, those relating to the orientation of tRNA on the 50 S subunit as studied by site-directed cross-linking techniques. A corresponding model for the 16S RNA within the 30 S subunit has already been described, and here a site-directed cross-linking approach is being used to determine the path followed through the subunit by messenger RNA. PMID- 2207174 TI - Escherichia coli 30S mutants lacking protein S20 are defective in translation initiation. AB - The 30S ribosomal subunits derived from Escherichia coli TA114, a a temperature sensitive mutant lacking ribosomal protein S20, were shown to be defective in two ways: (a) they have a reduced capacity for association with the 50S ribosomal subunit which results in the impairment of most of the functions requiring a coordinated interaction between the two subunits; (b) they are defective in functions which do not require their interaction with the large subunit (i.e., the formation of ternary complexes with aminocyl-tRNAs and templates, including the formation of 30S initiation complexes with fMet-tRNA and mRNA). The 30S ( S20) subunits seem to interact normally with both template and aminoacyl-tRNA individually, but appear to be impaired in the rate-limiting isomerization step leading to the formation of a codon-anticodon interaction in the P site. PMID- 2207173 TI - The conformation of the initiator tRNA and of the 16S rRNA from Escherichia coli during the formation of the 30S initiation complex. AB - The conformation of the E. coli initiator tRNA and of the 16S rRNA at different steps leading to the 30S.IF2.fMet-ARN(fMet).AUG.GTP complex has been investigated using several structure-specific probes. As compared to elongator tRNA, the initiator tRNA exhibits specific structural features in the anticodon arm, the T and D loops and the acceptor arm. Initiation factor 2 (IF2) interacts with the T loop and the minor groove of the T stem of the RNA, and induces an increased flexibility in the anticodon arm. In the 30S initiation complex, additional protection is observed in the acceptor stem and in the anticodon arm of the tRNA. Within the 30S subunit, IF2 does not significantly shield defined portions of 16S rRNA, but induces both reduction and enhancement of reactivity scattered in the entire molecule. Most are constrained in a region corresponding to the cleft, the lateral protrusion and the part of the head facing the protrusion. All the reactivity changes induced by the binding of IF2 are still observed in the presence of the initiator tRNA and AUG message. The additional changes induced by the tRNA are mostly centered around the cleft-head-lateral protrusion region, near positions affected by IF2 binding. PMID- 2207175 TI - A deletion mutation at the 5' end of Escherichia coli 16S ribosomal RNA. AB - A deletion of five nucleotides was introduced at the 5' end of the Escherichia coli 16S rRNA gene cloned in an appropriate vector under control of a T7 promoter. The 16S rRNA generated by in vitro transcription could be assembled into 30S subunits. The deletion did not affect the efficiency of translation of natural messengers and the correct selection of the reading frame. However, it reduced the binding of the messengers, which suggests that the 5' end of 16S rRNA is located on the pathway followed by the messengers on the 30S subunits. The deletion also restricted the stimulation of misreading by streptomycin in a poly(U)-directed system. This is in accord with the proximity of the 5' end of 16S rRNA to proteins S4, S5 and S12, which are known to be involved in the control of translational accuracy. PMID- 2207176 TI - Batroxostatin, an Arg-Gly-Asp-containing peptide from Bothrops atrox, is a potent inhibitor of platelet aggregation and cell interaction with fibronectin. AB - A potent inhibitor of platelet aggregation and cell adhesion was isolated from the venom of Bothrops atrox. This peptide, referred to as batroxostatin, was composed of 71 amino acids and showed a high degree of homology with other snake venom peptides including trigramin, albolabrin, elegantin and applagin: all 12 cysteines and the RGD sequence (standard one-letter amino acid codes) aligned in the same position. Compared on a molar basis, the anti-platelet aggregation activity of batroxostatin was about 1000-times higher than that of RGDS. In addition, batroxostatin was about 400-times more potent than GRGDS at inhibiting melanoma cell adhesion to fibronectin. Batroxostatin covalently attached to plastic promoted adhesion of melanoma cells. The anti-GP140 antibody, recognizing beta 1 integrins, completely inhibited adhesion of mouse melanoma cells to batroxostatin. This observation, in addition to the inhibitory effect of batroxostatin on the adhesion of chick fibroblasts to fibronectin, suggests that batroxostatin interacts with integrins from both the beta 1 and beta 3 subfamilies. PMID- 2207177 TI - Homocysteine uptake by human umbilical vein endothelial cells in culture. AB - The characteristics of the uptake of L-homocysteine by cultures of human umbilical vein endothelial cells have been examined. Uptake occurred by Na(+) dependent and Na(+)-independent systems, but was essentially independent of the pH of the uptake medium. The Na(+)-independent system corresponded to system L, being totally inhibited by the presence of beta-2-aminobicyclo(2,2,1)heptane-2 carboxylic acid (BCH) a system L analogue. It was concluded on the basis of starvation experiments coupled with failure to detect any inhibition in the presence of 2-methylaminoisobutyric acid (MeAIB), a system A analogue, that the Na(+)-dependent uptake was wholly accounted for by system ASC. The kinetic properties of systems L and ASC were determined by omitting Na+ from the uptake medium and incorporating BCH in the medium, respectively. It has been concluded on the basis of the inhibitory effects of a number of amino acids that uptake of homocysteine occurs by those systems which transport cysteine. PMID- 2207178 TI - Casein kinase 2: an 'eminence grise' in cellular regulation? PMID- 2207179 TI - In vitro linoleic acid activation of protein kinase C. AB - The importance of membrane fluidity in the activation of protein kinase C (PKC) was examined using the membrane fluidizer, linoleic acid, in a well-defined model membrane system. Biochemical and biophysical properties of the system were monitored. Linoleic acid activated PKC to a level of 50% of that observed for diacylglycerol. In contrast, linoleic acid did not directly interact with the phorbol ester binding site as did diacylglycerol. This was determined by the lack of involvement of the ionizable group of the fatty acid with activity and the enhancement of phorbol ester binding by linoleic acid and its ester analogs. The membrane fluidity of this model membrane system in the presence of linoleic acid was increased as determined by fluorescence polarization. This increased the availability of phospholipids, thus, explaining the linoleic acid-induced enhancement of phorbol ester binding. The PKC conformation as determined from intrinsic tryptophan fluorescence spectra was different for lipid mixtures containing linoleic acid or diacylglycerol correlating with the difference in biochemical activation properties. This study provides evidence that membrane fluidization is not the predominant function of the lipid activator in PKC activation, but may play a role in obtaining the preferred membrane state for maximal activation. PMID- 2207180 TI - Effect of isoproterenol analogs on the polypeptide composition of mouse parotid glands: relationship to enhanced growth. AB - The chronic administration of isoproterenol ((+-)-1-(3,4)-dihydroxyphenyl)-2 isopropylaminoethanol) induces both the accumulation of a family of secretory polypeptides (polypeptides C, D, E, F and G) and growth in size in mouse parotid glands. Eleven isoproterenol analogs including minor structural modifications either at the aromatic ring, at the ethanol-derived residue or at the end group bonded to the amino of the side chain, were analysed regarding their ability to produce those two responses. Analogs were distributed into two groups, namely inducers and noninducers. Inducer isoproterenol analogs provoked a massive accumulation of polypeptides C, D, E, F and G and were active in producing parotid gland enlargement. Noninducer isoproterenol analogs produced neither changes in the polypeptide composition nor growth response in these glands. Thus, a correlation between accumulation of polypeptides C, D, E, F and G and the growth in size response in parotid glands was more firmly established. In considering the chemical structure of the isoproterenol analogs with regard to their inducer or noninducer character, the three main domains taken into account appeared to participate in the inductive process. However, while an intact ethanol-derived domain was found to be absolutely necessary for the inductive ability of the analogs, both the aromatic ring as well as the substituent on the side-chain amino group could experience several modifications without resulting in loss of the inductive character. PMID- 2207182 TI - [Determination of the folding of globular protein chain by the self-consistent field method]. AB - It is shown that and how it is possible to single out the chain fold which is thermo-dynamically most stable. The suggested approach is based on two physical ideas: A "molecular field" approximation permits to examine all protein structures which belong to the same "folding pattern". Only a limited set of the "potentially stable" folding patterns have to be examined. The general approach is illustrated by calculations of the stable folds for two beta-domains. PMID- 2207181 TI - [Heat transitions in DNA molecule. The life-time of excited h-b-1 hydrogen bond in paired guanine-cytosine bases]. AB - A theory of radiationless transitions of protons of the hydrogen bonds between the paired DNA bases is constructed. The lifetime of excited h-b-1 bond in guanine-cytosine pair is found to be 4.6 x 10(-9) sec. The dependence of frequencies, amplitudes and normal coordinates of heavy atoms (N, O) on the state of H-bond (ground or excited) are taken into account. PMID- 2207184 TI - [Study of thermal denaturation of the rod part of myosin molecule by microcalorimetry and intrinsic fluorescence methods]. AB - Thermal denaturation of myosin rod has been studied by differential scanning microcalorimetry and intrinsic tryptophane fluorescence methods. Use of the sequence annealing in the calorimetric measurement allows to decompose the total thermogram of rod into four elementary bands with maxima at 42, 46.5, 50 and 57 degrees C. Fluorescence changes occur at temperatures which coincide with the first, second and fourth calorimetric peaks. Changes of the time resolved and steady state fluorescence of myosin rod were interpreted using the data on localization of tryptophan residues in the molecule. The tryptophan fluorescence of myosin rod is assumed to monitor the denaturational changes in high meromyosin and probably in the hinge region but not in the subfragment 2. PMID- 2207183 TI - [Calorimetric study of aqueous solutions of histone H1 and poly-L-proline II at low temperatures]. AB - Low temperature differential scanning microcalorimetric investigation of water histone H1 and water-poly-L-proline investigation was carried out. The concentrational dependence of the thermodynamic parameters (delta H(C), Tmax(C), delta S(T, C] for "bulk" water layers were studied. It was shown that the influence of these macromolecules on the structure and properties of surrounding water layers at the same degree of hydration is different. PMID- 2207186 TI - [Relation between H2 production and energy-dependent metabolism of H+ and K+ ions in E.coli]. AB - Anaerobically grown E. coli escape H2 into the medium during the operation of H(+)-K(+)-pump exchanging 2H+ from a cell for one K+ of the medium. Anaerobic cells grown in the nitrate medium as well as the aerobically grown bacteria possessed neither 2H+/K+ exchange system, nor the ability for H2 production. Introduction of N,N'-dicyclohexylcarbodiimide into the medium, the removal of external K+ or the decrease of external osmotic pressure blocked both the functioning of H(+)-K(+)-pump and H2 production. The substitution of glucose by lactate reduced the activity of bacteria without change in pump operation and H2 production. It is assumed that formate-hydrogen lease and H(+)-K(+)-pump are working in collaboration. PMID- 2207187 TI - [A model of coordination of sperm flagella movement]. AB - The periodicity of bulls and humans' spermatozoa motion is investigated. The period of their motion is divisible by 24 and 15 turns of spermatozoa heads respectively. The interrelation of the observed periodicity with the ultrastructure of gamete tails is pre-supposed. A model of mitochondrial coordination of sperm flagella movement is proposed. PMID- 2207185 TI - [Accumulation of UV-induced radicals in proteins with various degree of aggregation]. AB - Accumulation of radicals UV-induced in protein solutions at 77 K was investigated. It has been found that in each molecule of small proteins true solutions only one ionization proceeds and two radicals are formed. The limiting number of radicals per one protein molecule decreases with the increase of their aggregation level. A method is suggested for observing aggregation and desegregation processes in proteins, as well as a method for determining the absolute concentration of radicals. PMID- 2207188 TI - [Absence of small-angle maximums on the x-ray images of ocular lens tissue]. AB - X-ray small-angle scattering study of bovine lens tissue was carried out. It was shown that X-ray patterns of lens cortical and nuclear native tissues did not contain the small-angle maxima. The maximum in the range of 15-20 nm Bragg distance appeared as a result of the lens tissue partial dehydration. Earlier such maximum was considered by some authors as the evidence of crystallin proteins short-range order in the native lens. Now it is confirmed to be a preparative artefact of dehydration. It was shown also that similar maximum in 15 20 range existed in the case of concentrated crystallin solutions. This indicates that supramolecular organization of crystallins in the native lens is not similar to that in the concentrated solution. PMID- 2207189 TI - [A model of diffusion of anti-cataract drugs into the lens tissue]. AB - For modeling anticataract drugs diffusion into the lens surface tension of drugs, their solubility in nonpolar solvent and drug adsorption at air-water and water lipid monolayer surface were measured. It has been shown that diffusion of many drugs into the lens is limited by their low solubility in a monolayer phase of the membrane. Catachrom concentration in the lens should be the highest, because it can concentrate at interfaces. PMID- 2207190 TI - [The effect of blood flow velocity on the process of thrombus formation in microvessels]. AB - The growth rate constant of platelet thrombi as a function of mean blood flow velocity was studied using mesentery vessels of the white rat. An advanced mathematical model for the kinetics of platelet thrombi was developed. The dependence of platelet activation delay time upon the distance from the damaged vessel wall is pointed out as a result of theoretical and experimental data comparison. PMID- 2207191 TI - [Mathematical model of movement of asymmetrical erythrocyte along the capillary]. AB - The proposed 3-dimensional mathematical model describes the motion of asymmetrical erythrocytes through capillaries of different sections. The lubrication theory is used to describe the flow of the suspending fluid in the gaps between the cell and the vessel wall. It is shown that the cell velocity and diameter of the capillary defines the value of the resistance of erythrocyte motion. PMID- 2207193 TI - [Relation between the excitatory synaptic currents and clamped somatic potential in the model of neuron with nonlinear dendrites]. AB - The influence of the clamped somatic potential on the excitatory synaptic current (EPSC) was studied in the model of the dendrite with N-shaped instantaneous stationary current--voltage curve. Proximal EPSC diminish and become narrower with decreasing hyperpolarization or modest depolarization, distal EPSC increase and become wider, intermediately distant EPSC change insignificantly. Under increasing depolarization all the EPSC become significantly wider and larger. EPSC facilitate stable depolarization of the dendrites. When the dendrite is stable depolarized EPSC becomes very small and narrow, but it becomes larger and wider as the soma is hyperpolarized. EPSC becomes especially large and wide when the soma is hyperpolarized just to terminate the stable depolarization of the dendrite branch where the active synapses are located. The model explains certain phenomena which are difficult to understand by the theory of ohmic dendrites. New phenomena are predicted. PMID- 2207192 TI - [Drift of vortex in the myocardium]. AB - The behavior of a vortex in rabbit myocardium with artificial inhomogeneity was studied using mapping technique. The inhomogeneity was created by perfusion of a part of the preparation with quinidine solution. Quinidine increased the refractory period of the myocardium and diminished the conduction velocity. It has been found that the vortex drifts along the border of the inhomogeneity because of the difference of refractory periods. The drift velocity was about 4 cm/s, which was five times less than the wave velocity. The direction of the drift was determined by the vector (----omega X----delta R), where ----omega is the angular velocity of vortex rotation, and ----delta R is a gradient of the refractory period. PMID- 2207195 TI - [The mechanism of setting the common rhythm of the pacemaker pair in the sinoatrial node]. AB - Principal physiological hypotheses concerning the setting of united rhythm in the heart sinoatrial node (SAN) are considered. A mathematical model of SAN is proposed which takes into account properties of individual elementary pacemakers and their interaction. Assuming paired interaction of the pacemakers there are revealed the main P.D. parameters, affecting the setting of the united rhythm. Quantitative expressions are obtained for the united rhythm period, delay and propagation velocity of the excitation. The calculated data are compared with the experimental ones. The hypothesis concerning the setting of the united rhythm as a result of the interaction of SAN pacemakers is confirmed. PMID- 2207194 TI - [Spatial selectivity of vestibular receptive fields of cerebellar Purkinje cells towards the orientation of angle accelerations]. AB - Using microcaloric stimulation of semicircular canals of the frog vestibular apparatus parameters of orientation sensitivity of the receptive fields of the cerebellum Purkinje cells towards angle accelerations were studied. A change of this sensitivity depending on the value of acting angle acceleration was shown. PMID- 2207196 TI - [A possibility of significant lowering the defibrillation current by determining the right time for application of a defibrillating pulse. A mathematical model]. AB - The effect of defibrillating pulses on the functionally determined re-entries (leading circles) was studied by computer simulation. Arrhythmias caused by different numbers of leading circles (from 1 to 18) were investigated. The defibrillation threshold was found to vary 2-4-fold, depending on the time of application of a pulse. At small currents the defibrillation mechanism is principally different from the commonly known one and is linked to the movement of leading circles towards each other or towards the boundary of the excitable tissue. PMID- 2207197 TI - [The effect of cell migration on the stability of immunogenic multicentric tumors]. AB - A mathematical model of the growth of multicentrical tumors under conditions of the tumor cells interactions with cytotoxic T-lymphocytes (CTL), natural resistant factors and cells and migration CTL between tumor focuses is presented. For any finite number of the tumor focuses at the comparatively low intensity migration of CTL the dynamic stability conditions among multicentrical tumors and the immune system were obtained. PMID- 2207198 TI - [A model of chemical memory of neuron]. PMID- 2207199 TI - Simulation study on dynamics transition in neuronal activity during sleep cycle by using asynchronous and symmetry neural network model. AB - We have found that single neuronal activities in different regions in the brain commonly exhibit the distinct dynamics transition during sleep-waking cycle in cats. Especially, power spectral densities of single neuronal activities change their profiles from the white to the 1/f along with sleep cycle from slow wave sleep (SWS) to paradoxical sleep (PS). Each region has different neural network structure and physiological function. This suggests a globally working mechanism may be underlying the dynamics transition we concern. Pharmacological studies have shown that a change in a wide-spread serotonergic input to these regions possibly causes the neuronal dynamics transition during sleep cycle. In this paper, based on these experimental results, an asynchronous and symmetry neural network model including inhibitory input, which represents the role of the serotonergic system, is utilized to examine the reality of our idea that the inhibitory input level varying during sleep cycle induce that transition. Simulation results show that the globally applied inhibitory input can control the dynamics of single neuronal state evolution in the artificial neural network: 1/f-like power spectral density profiles result under weak inhibition, which possibly corresponds to PS, and white profiles under strong inhibition, which possibly corresponds to SWS. An asynchronous neural network is known to change its state according to its energy function. The geometrical structure of network energy function is thought to vary along with the change in inhibitory level, which is expected to cause the dynamics transition of neuronal state evolution in the network model. These simulation results support the possibility that the serotonergic system is essential for the dynamics transition of single neuronal activities during sleep cycle. PMID- 2207200 TI - A dynamic theory of coordination of discrete movement. AB - The concepts of pattern dynamics and their adaptation through behavioral information, developed in the context of rhythmic movement coordination, are generalized to describe discrete movements of single components and the coordination of multiple components in discrete movement. In a first step we consider only one spatial component and study the temporal order inherent in discrete movement in terms of stable, reproducible space-time relationships. The coordination of discrete movement is captured in terms of relative timing. Using an exactly solvable nonlinear oscillator as a mathematical model, we show how the timing properties of discrete movement can be described by these pattern dynamics and discuss the relation of the pattern variables to observable end-effector movement. By coupling several such component dynamics in a fashion analogous to models of rhythmic movement coordination we capture the coordination of discrete movements of two components. We find the tendency to synchronize the component movements as the discrete analogon of in-phase locking and study its breakdown when the components become too different in their dynamic properties. The concept of temporal stability leads to the prediction that remote compensatory responses occur such as the restore synchronization when one component is perturbed. This prediction can be used to test the theory. We find that the discrete analogon to antiphase locking in rhythmic movement is a tendency to move sequentially, a finding that can also be subjected to empirical test. PMID- 2207201 TI - The study of locomotion by finite state models. AB - A methodology to derive finite state models of legged locomotion is outlined. Background data for model derivation are joint angle functions and gait diagrams. The method is used to describe the walking of the cat in terms of an abstract automaton. The main features of finite state descriptions of legged locomotion are described. Such models are presenting locomotion invariants of a species in explicit form. It is emphasized that finite state models provide insight into structural features of motor control organization such as decomposition into subsystems, interaction between centralized and decentralized control, and the role of control levels. The finite state model of locomotion can be helpful in suggesting experiments pertinent to the study of motor control and interpretation of experimental results. PMID- 2207202 TI - [pH-dependent changes in the two-stage kinetics of superprecipitation reaction of natural actomyosin]. AB - The effect of pH on the two-stage kinetics of the superprecipitation (SPP) reaction of natural actomyosin was investigated. It was shown that the experimental dependencies appear as two intersecting bell-shaped curves reflecting the effects of pH on individual steps of the SPP reaction which are mediated by different molecular mechanisms. It was supposed that the both reaction mechanisms involve actomyosin complexes which have different structural states and differ also by the degree of dissociation in the presence of ATP. The shifts in the dynamic equilibrium between the two states of actomyosin may induce pH-modulations in the two-stage kinetics of SPP and, presumably, ATPase. PMID- 2207203 TI - [Phenylalanyl-tRNA-synthase from human placenta: isolation and characteristics]. AB - Phenylalanyl-tRNA synthetase (EC 6.1.1.20) from human placenta was isolated and purified using fractionation with polyethyleneglycol and chromatography on hydroxylapatite, heparin-Sepharose and mono-S. The enzyme purified 14800-fold with a 8% yield had a specific activity of 260 U./mg. The molecular mass of the native enzyme as determined by gel filtration was 270 +/- 13 kDa. The molecular masses of the enzyme subunits according to SDS-PAGE data were 74 +/- 4 kDa (alpha subunit) and 63 +/- 3 (beta-subunit). The Km values for tRNA, ATP and phenylalanine in the aminoacylation reaction were 6.6 X 10(-8) M, 8.3 X 10(-5) M and 5.8 X 10(-6) M, respectively. PMID- 2207204 TI - [Comparative study of bovine adrenodoxin and renorenodoxin]. AB - The ferredoxin from bovine renal mitochondria (renoredoxin) has been obtained in a highly purified state. The A415/A280 ratio of the purified renoredoxin is 0.84. The absorption spectrum of renoredoxin was shown to be identical to that of bovine adrenodoxin. Two forms of renoredoxin (Mr 14200 and 13300) were detected by using polyacrylamide gel electrophoresis. These forms exhibit a very similar immunologic cross-reactivity with polyclonal antibodies to adrenodoxin. The N terminal amino acid sequence of renal ferredoxin was shown to be identical to that of adrenodoxin; the C-terminal sequences of both ferredoxins undergo a similar post-translational proteolytic modification. The amino acid composition of ferredoxins are also very close. Renal ferredoxin can be replaced by adrenodoxin in reconstituted systems from bovine adrenal cortex mitochondria which catalyze the side chain cleavage of cholesterol to pregnenolone and the 11 beta-hydroxylation of deoxycorticosterone to corticosterone. PMID- 2207207 TI - [The effect of phorbol esters and Ca2+ ions on the process of autophosphorylation of epidermal growth factor receptor in vivo]. AB - Monoclonal antibodies against phosphotyrosine were used to study tyrosine phosphorylation in human epidermal carcinoma A431 cells in vivo. Incubation of A431 cells with the epidermal growth factor (EGF) leads to tyrosine phosphorylation of the EGF receptor; the phosphotyrosine content in cellular EGF receptors increases 50-100-fold in the presence of the growth factor. The maximum level of the receptor autophosphorylation is reached on the 5th min and is then held constant during 90-min incubation with EGF. After preincubation of A431 cells with phorbol-12-myristoyl-13-acetate (PMA) or calcium ionophore A23187 the receptor autophosphorylation decreases significantly. After addition of A23187 and EGTA to the preincubation medium the phosphotyrosine content in cellular EGF receptors stimulated by the growth factor reaches the control level i.e., that observed in the absence of the ionophore. After preincubation of cells in the presence of phorbol ester and H-7 (protein kinase C inhibitor) the level of EGF receptor autophosphorylation does not practically differ from that of control. PMID- 2207205 TI - [pH-dependence of hormone-binding and enzymatic activity of estrophilic hydroxysteroid dehydrogenase from the rabbit liver]. AB - The effects of pH on the ability of NADP-dependent estrophilic hydroxysteroid dehydrogenase (HSD) from the soluble fraction of rabbit liver to bind steroids and catalyze their 3 alpha, 3 beta, 17 beta- and 20 alpha-oxidoreduction were studied. The pH optima for enzymatic transformations of various steroids were found to differ significantly by more than two units. These differences do not seem to be related to the localization of the modified group in the steroid molecule. Kinetic data suggest that pH influences the catalytic efficiency, steroid affinity for the protein and, perhaps, the degree of interdependence of steroid and cofactor binding to the protein. These assumptions were confirmed by the results of direct 3H-steroid-HSD binding studies. Furthermore, the maximal levels of binding of various steroids to the protein were found to occur at pH values differing by more than 4 units. Scatchard analysis revealed the effects of hydrogen ion concentrations both on the steroids affinity for the protein and on the concentration of steroid-binding sites of HSD. The data obtained are suggestive of some "superfluity" of the protein steroid-binding site which, in turn, ensures the multifunctionality of estrophilic HSD including a possibility of an alternative orientation of steroids in their binding site. PMID- 2207206 TI - [Synthesis of phosphocreatine in heart mitochondria of rats with hyperthyroidism]. AB - The mechanisms of the phosphocreatine/creatine ratio decrease in female Wistar rats with hyperthyroidism were studied. L-Thyroxin was injected to animals in doses of 50 and 100 micrograms/100 g of body weight, daily for 1 and 2 weeks. Oxidative phosphorylation and the rate of phosphocreatine synthesis were studied in isolated rat heart mitochondria. It was found that hyperthyroidism caused an increase in the ADP-activated mitochondrial respiration, whereas the coupling between electron transport and ADP phosphorylated remained at a constant level. Besides oxidative phosphorylation, activation, hyperthyroidism increased the rate of phosphocreatine synthesis at high values of the phosphocreatine/oxygen ratio. Thus, hyperthyroidism is unaccompanied by and significant changes in the coupling of mitochondrial creatine kinase with oxidative phosphorylation. PMID- 2207208 TI - [Thiol-dependent serine proteinase from Streptomyces thermovulgaris]. AB - The cultural filtrates of S. thermovulgaris contain a proteinase which is active towards the chromogenic subtilisin substrate, Z-Ala-Ala-Leu-pNa, and azocasein. Pure enzyme preparations were obtained by affinity chromatography on bacitracin Sepharose with subsequent rechromatography on the same adsorbent. The proteinase was completely inactivated by PMSF and DFP, the specific inhibitors for serine proteinase, by thiol reagents (HgCl2, PCMB) and by the protein inhibitor from S. jantinus. The pH activity optimum for the enzyme is 7.8-8.2, temperature optimum is 55 degrees C. The enzyme is stable at pH 6-9, has a pI of 5.0 and a molecular mass of 32 kDa. When tested against the peptide substrate, the enzyme shows a specificity characteristic for subtilisins. The N-terminal sequence of the enzyme, Tyr-Thr-Pro-Asn-Asp-Pro-Tyr-Phe-Ser-Ser-Arg-Gln-Tyr-Gly, shows a 100% homology with that of terminase, a thiol-dependent serine proteinase. On the basis of the above considerations the enzyme may be related to the subfamily of thiol-dependent serine proteinases. PMID- 2207210 TI - [Methylation of Eco RI (GAm'ATTC) sequences of bacterial DNA]. AB - The methylation of Eco RI (GAm6 ATTC) sequences of DNA of bacteria related to the main branches of their phylogenetic dendrogramme, was studied. It was found that methylation of Eco RI sites is observed in bacteria Caulobacter and in Thermus aquaticus. This finding can be substantiated by the resistance of these DNAs to Eco RI restrictase as well as by the fact that Bam HI fragments of these DNAs cloned within the composition of the vector plasmid pUC8 in E. coli cells contain GAATTC sites. PMID- 2207209 TI - [Kinetic characteristics and enantioselective action of penicillinase in the hydrolysis reaction of N-phenylacetyl derivatives of 1-aminoethylphosphonic acid and its esters]. AB - Penicillin acylase from E. coli (EC 3.5.1.11) was found to hydrolyze N phenylacetylated 1-aminoethylphosphonic acid and its esters. The enzyme preferentially converts the R-form of the substrates: the ratios of the bimolecular rate constants of penicillin acylasecatalyzed hydrolysis of R- and S forms of 1-(N-phenylacetamino)-ethylphosphonic acid and its dimethyl- and diisopropyl-esters are 58000, 2300, 1800; these derivatives were shown to have the greatest values of the catalytic constants for enzymatic hydrolysis of all known substrates for penicillin acylase: 237, 148 and 134 s-1; the corresponding Km values are 3.7 10(-5), 6.8 10(-4) and 6.2 10(-4) M at pH 7.0. The kinetics of enzymatic hydrolysis of 1-(N-phenylacetamino)-ethylphosphonic acid was investigated up to high degrees of conversion. The inhibition of penicillin acylase by high concentrations of the R-form of the substrate (with substrate inhibition constant of 0.07 M) and competitive inhibition by the reaction product, phenylacetic acid (Ki = 3.5 10(-5) M), was observed. PMID- 2207211 TI - [Interaction of sodium tetraphenylborate with serum lipoproteins]. AB - An addition of tetraphenylboron (TPB) at low values of pH results in the formation of a cholesterol-rich pellet after centrifugation. The pellet contains 90-95% of whole serum cholesterol. The pH effectiveness sequences for TPB precipitation of low density lipoproteins are detected. It is assumed that TPB changes the distribution of the charges in the hydrophobic moiety of lipoproteins and increases their ability to precipitate. PMID- 2207212 TI - [Vitamin A and microsomal membranes: the effect of retinol deficiency on lipid microviscosity and phospholipid turnover in rat liver microsomes]. AB - Studies with the use of the fluorescent probe pyrene revealed that vitamin A deficiency in maturing male rats results in the increased microviscosity of liver lipids. This effect seems to be due to changes in the lipid composition of microsomal membranes (increased cholesterol/phospholipid ratio and lowered polyunsaturated fatty acid content) as well as to the low level of retinol. Analysis of microsomal phospholipids labeled with [3H]palmitate and [14C]glycerol revealed that vitamin A deficiency accelerates the turnover of the glycerol skeleton but sharply decelerates that of fatty acid residues. It is concluded that the observed effect of retinol on the structural and functional properties of biological membranes is due to its ability to control the microviscosity and turnover of membrane lipids. PMID- 2207214 TI - [The characteristics of sarcoma M-1 in rats]. AB - Some biochemical characteristics of rat sarcoma M-1 transplanted into skeletal muscle have been investigated. Data on the key enzyme activity of the carbohydrate metabolism on the different stages of neoplasia are reported. The isozyme content and intracellular location of hexokinase in sarcoma M-1 have been studied specially. PMID- 2207213 TI - [The action of osmotic shock on blood cell populations]. AB - The effect of osmotic shock on human lymphocytes receptors is investigated. The patients are shown to be varied in terms of osmotic stability of lymphocytes, although under osmotic shock the decrease of cell share with definite immunological markers is observed in all cases. It is characteristic of all T lymphocyte populations. The incubation of non-diluted blood with carnosin preserves largely the investigated receptors at osmotic shock. It is suggested that described modifications in lymphocyte receptor system connect with immunocorrective effect of the hypoosmotic blood. PMID- 2207216 TI - [The demonstration of an extramembranous location for the putative amphipathic helix of the acetylcholine receptor]. AB - It has been demonstrated that the lysyl residues at the centers of the potential amphipathic helices of the alpha- and beta-subunits could be readily labeled in native acetylcholine receptor with anionic electrophiles. This result indicates that the regions in the sequences of the alpha- and beta-polypeptides which patterns of hydropathy are those of amphipathic helices are fully exposed on the surface of the native protein and do not span the membrane. PMID- 2207215 TI - [The in vivo production of corticosteroids by the adrenals in rats of the SSHR hypertensive strain]. AB - The review contains the hormonal characteristic of the line of stress sensitive hypertensive rats (SSHR) developed from normotensive Wistar rats (WR) during genetic selection. The in vivo production mineralo- and glucocorticoids by rat adrenal glands is estimated. It is shown that SSHR have an increased level of glucocorticoids. The biochemical features of pathogenesis of essential hypertension are discussed. PMID- 2207217 TI - Estrogen replacement in postmenopausal disorders. PMID- 2207218 TI - Normal latency of the P300 event-related potential in mild-to-moderate Alzheimer's disease and depression. AB - A two-tone-discrimination task was used to elicit the P300 component of event related (brain) potentials (ERPs) from patients with presumed Alzheimer's dementia of mild or moderate severity, depressed patients of older age, and cognitively normal individuals. Although the average P300 latency of the Alzheimer patients was greater than that of the depressed patients, which in turn was greater than that of older aged normals, none of the group differences in latency were statistically significant. Moreover, when latency was examined on an individual basis, less than one-quarter of the Alzheimer patients had an abnormally delayed P300 for their age. Reaction times and the percentage of correct behavioral responses to the tones did distinguish the Alzheimer from the normal group; on both measures the patients' scores were significantly worse. It was concluded that the performance of a simple tone discrimination task requiring a button-press response does not sufficiently tax those cognitive functions impaired in the earlier stages of Alzheimer's dementia to result in abnormally slowed cognitive processing of the kind reflected in P300 latency. PMID- 2207219 TI - Clomipramine in obsessive-compulsive disorder. AB - The effects of clomipramine hydrochloride (CMI) versus placebo upon DSM-III defined obsessive-compulsive disorder (OCD) were assessed in a 10-week double blind multicenter trial and in a corresponding 1-year double-blind extension study. The NIMH global O-C scale, a 15-point ordinal severity scale, incorporating categorical features specific to OCD, was used to evaluate the severity of obsessive compulsive symptoms over the course of treatment, and a physician's rating of global therapeutic effect was used to assess overall change from baseline. In the core study, patients receiving placebo demonstrated minor and nonsystematic changes, whereas patients who received CMI had clinically and statistically significant reductions in the global severity of their disorder. Findings from the extension study were consistent with continuing efficacy for CMI, whereas corresponding data for patients receiving long-term placebo were difficult to interpret. Based upon shifts in categorical severity, symptoms for over half those patients who received CMI were rendered subclinical or within a range of normal functioning. In contast, less than 5% of patients receiving placebo had their symptoms reduced to a subclinical level. Generally, both treatments were well tolerated. Previous studies have indicated therapeutic potential for CMI in obsessive compulsive disorder. These findings confirm and extend previous observations. PMID- 2207220 TI - Rapid dynamic CT scanning in primary degenerative dementia and age-matched controls. AB - Dynamic computed tomography (CT) scanning of the brain was performed in 26 patients with primary degenerative dementia (PDD) and in 15 age-matched controls without evidence of a dementing illness. Changes in CT density values over time were obtained for 16 regions of interest (ROIs) that were carefully chosen to avoid overlap with adjacent cerebrospinal fluid (CSF), sulsi, or bone. CT density washout curves were compared between patients and controls to detect regions where blood brain barrier (BBB) permeability might be increased. Although the patients' washout curves declined more gradually than control curves in 11 of the 14 ROIs with a functioning BBB, in no case did the difference reach statistical significance. Intrarater correlation coefficients indicated good overall reliability in the selection of ROIs. PMID- 2207221 TI - Eating disorders and depression: is there a serotonin connection? AB - Central serotonin pathways modulate eating patterns, and may also participate in the regulation of behavioral impulsivity and mood. Recent studies lend support to the hypothesis that impaired postingestive satiety in bulimia nervosa is associated with reduced hypothalamic serotonergic responsiveness. Serotonin dysregulation has been implicated in major depression, and may play a role in the increased prevalence of depressive episodes in patients with eating disorders. This review compares evidence for alterations in central serotonin regulation in patients with anorexia nervosa, bulimia nervosa, and depression. It is proposed that impaired synaptic transmission in functionally distinct serotonin pathways may result in concurrent or sequential periods of binge eating, behavioral impulsivity, and depression in patients with eating disorders. PMID- 2207222 TI - Implications of age of onset for the genetics of schizophrenia. PMID- 2207223 TI - Imipramine effects on sleep in depressed adolescents: a preliminary report. PMID- 2207224 TI - In vivo leucocyte interactions on Pellethane surfaces. AB - In vivo leucocyte interactions of three Pellethane materials of varying hardness were qualitatively and quantitatively characterized using a cage implant system over a 21 d implantation period. Scanning electron microscopy (SEM) and cytochemical staining were utilized to observe the cellular events occurring at the leucocyte-biomaterial interface. Many of the quantitative assays performed, the intracellular alkaline phosphatase activity of exudate leucocytes, the intracellular acid phosphatase activity of adherent leucocytes, the density of adherent leucocytes and the foreign body giant cell network formation tendencies of adherent leucocytes, suggest increased cellular activation with increased Pellethane hardness. Qualitative SEM evaluation of Pellethane surfaces revealed a variety of cellular activities. These included macrophage adherence, cytoplasmic spreading and macrophage-macrophage membrane fusions to form foreign body giant cells. The foreign body giant cells exhibited nuclear reorganization and, when compared with adherent macrophages, they displayed an enhanced ability to fuse to neighbouring leucocytes, increased spreading of membrane processes over the polymer surface, the presence of large cytoplasmic vacuoles, and a lengthened duration of enzymatic activity. Contact angle analysis showed the Pellethane surfaces to be hydrophobic and of low hysteresis. The critical surface tension and the dispersive component of the total surface tension were found to increase with Pellethane hardness. PMID- 2207225 TI - Adhesion of carboxylate cements to hydroxyapatite. III. Adsorption of poly(alkenoic acids). AB - Investigations into the effects of relative molecular mass (RMM) and structure of poly(alkenoic acid)s on their adsorption on to hydroxyapatite (HAP) were carried out with a view to establishing factors that influence the adhesion of glass poly(alkenoic acid) cements to tooth material. The effects of pH and fluoride addition were also studied. It was found that high adsorption levels were achieved under conditions of high chain entanglement, such as in a concentrated solution of a polyacid of high RMM. Theories of adsorption of carboxylic acids on to HAP are reviewed in the light of these studies and previous work at our laboratory. PMID- 2207226 TI - Mechanisms of blood coagulation induced by latex particles and the roles of blood cells. AB - Latex particles with highly negative or positive charges shortened the clotting time of whole blood and platelet-rich plasma and activated platelet factor 3. Platelet-poor plasma was clotted by the particles with a highly negative charge, but not by those with a positive charge, except hydrophobic particles. Blood coagulation by positively-charged particles was attributed to platelet activation. An enhancement of blood coagulation was also observed in the presence of erythrocytes, leucocytes, their cell membranes or negatively charged phospholipids, and phosphatidylserine instead of platelets. Hydrophilic and low charged particles suppressed blood coagulation. PMID- 2207227 TI - Kinetics of colonization of a porous vitreous carbon percutaneous implant. AB - Implants of porous vitreous carbon with pore diameters 200-500 microns were surgically placed in rabbits and pigs. Skin colonization experiments were carried out by topically inoculating concentrations of Staphylococcus aureus and Escherichia coli in a test area adjacent to the implant and to a remote control area. Subsequent swab cultures were taken at 6, 24, 48 and 72 h and one or more weeks. In vitro attachment studies were also performed using bacteria stained with FITC on 1 mm slices of the porous carbon. Proplast was used as a control. Results showed that despite a temporary high rate of colonization and obvious binding of the bacteria to the carbon, the skin-implant interface resists infection by both normal and pathogenic flora. PMID- 2207228 TI - Silicone rubber-hydrogel composites as polymeric biomaterials. I. Biological properties of the silicone rubber-p(HEMA) composite. AB - A composite material was prepared consisting of silicone rubber matrix and particulate lightly cross-linked poly(2-hydroxyethyl methacrylate) (p(HEMA] hydrogel. The material resembling common silicone rubber is hydrophilic and swells in water like hydrogels. The effects of the implanted composite on tissues of the living organism were tested in rats by methods assessing local acute and chronic inflammatory reactions and calcification by means of radioactive indicators and by histological examination. Results of a 6 month implant study indicated no difference in reactions of the animal body on the silicone rubber p(HEMA) composite and a non-toxic, non-irritant pure solid p(HEMA) control. PMID- 2207229 TI - Silicone rubber-hydrogel composites as polymeric biomaterials. II. Hydrophilicity and permeability to water-soluble low-molecular-weight compounds. AB - The surface and transport properties of water-swollen silicone rubber-hydrogel composites were investigated. Surface wettability of these materials, composed of a polysiloxane matrix and the hydrogel phase consisting of very fine particles of lightly cross-linked poly(2-hydroxyethylmethacrylate), increased markedly with increasing content of the hydrogel phase. For composite materials containing a lightly cross-linked 2-hydroxyethylmethacrylate (HEMA)-methacrylic acid (MAA) copolymer and polymethacrylic acid (PMAA) as the hydrogel phase, permeability to water-soluble organic compounds and drugs were measured. The permeability varied within a broad range depending on the composition and content of the hydrogel phase. High permeation rates could be obtained while still retaining relatively fair mechanical properties. Relationships between the composition of silicone rubber-hydrogel composites, their structure and the permeation coefficients of the individual permeates are discussed. PMID- 2207230 TI - Measurement of the fracture toughness of some contact lens hydrogels. AB - The fracture toughness of three polymethacrylate contact lens hydrogel materials was measured using the method of Generalized Fracture Mechanics. One hydrogel (SNOFLEX S68) had a significantly higher fracture energy per unit area (Jc) than the others, probably because it undergoes plastic deformation at high strains. Differences in toughness imply differences in the mechanical durability of the contact lenses in normal use, which could not be so readily deduced from the results of tensile strength tests. PMID- 2207231 TI - Antithrombogenic pO2 sensor for continuous intravascular oxygen monitoring. AB - An antithrombogenic oxygen partial pressure sensor (Anthron pO2 sensor) was produced by coating a hydrophilic heparinized polymer (Anthron) on an etched epoxy composite ultramicroelectrode (microhole electrode). From in vitro tests, both the response time and stability were satisfactory under the conditions of a 20 microns thickness of Anthron coating and a depth up to 100 microns for the microhole. Additionally, results of in vitro tests without systemic heparinization demonstrated that a stable real time measurement of the intravascular oxygen partial pressure value was possible for a long period without thrombus formation or adhesion of blood components on the electrode surface of the Anthron pO2 sensor. Moreover, the measured data agreed with those from the blood gas analyser. Due to the thick thrombus formation on the electrode surface, the control (non-coated) sensor was unable to measure the intravascular oxygen partial pressure even for a short period of time. PMID- 2207233 TI - Plasmatic antiproteinase activity enhancement by insoluble functionalized polystyrene surfaces. AB - Antithrombogenic functional polymer surfaces have been obtained by grafting heparin or by substituting insoluble polystyrene with sulphonate and/or amino acid sulphamide groups. Their heparin-like properties have been related to their catalytic effects on the antithrombin III - thrombin complex formation. Amongst these antithrombogenic surfaces, this study demonstrates that some insoluble amino acid sulphamide derivatives of polystyrene strongly potentiate heparin cofactor II, in addition to antithrombin III. In contrast, an insoluble polystyrene sulphonate and, to a lesser extent, an insoluble heparin copolymer, are better catalysts of antithrombin III. It is hypothesized that such different behaviours result from different conformations of the species adsorbed onto the surfaces. The conclusions support the possible use of such amino acid sulphamide groups to prepare antithrombogenic surfaces in contact with blood. PMID- 2207232 TI - Low-friction hydrophilic surface for medical devices. AB - A hydrophilic polymer surface was developed exhibiting excellent low frictional property, namely slipperiness, when in contact with water or physiological fluid due to the reaction of epoxy-containing poly(vinyl pyrrolidone) with the polyamino compound formed on the surface of the substrate. Epoxy-containing poly(vinyl pyrrolidone) was obtained by the copolymerization of vinyl pyrrolidone as a hydrophilic component, glycidyl acrylate as a binding component to the substrate, and vinyl acetate to preserve the strength of the coating layer. The surface friction coefficient depends on the molecular weight of the coated hydrophilic copolymer. It was demonstrated that a molecular weight of 400,000 or more is essential to achieve excellent low surface friction. Using rabbit models, polyurethane catheters, both with and without the hydrophilic low friction coating, were evaluated for surface friction coefficient and blood compatibility. As a result, in the case of coated catheters, no lesions of the intima of the blood vessels and no thrombus formations on the surfaces of the catheters were observed. However, the non-coated catheters injured the intima of the blood vessels and severe thrombus formation was found on their surfaces. PMID- 2207234 TI - Physico-chemical properties of silk fibroin membrane as a biomaterial. AB - A water-insoluble silk fibroin membrane was prepared by immersing a silk fibroin membrane as cast in 50 vol% aqueous methanol solution for different periods of time at 25 degrees C. To use the membrane as a biomaterial, oxygen and water vapour permeability, transparency, mechanical property and enzymatic degradation behaviour in vitro of the membrane in the wet state were investigated. These physico-chemical properties changed according to the condition of the methanol treatment. The membrane had oxygen permeability, water vapour permeability, transparency and biodegradability. PMID- 2207235 TI - Dissolution mechanism of zinc phosphate dental cement in acetic and lactic acid buffers. AB - When zinc phosphate cement was immersed in 0.1 M acetic and lactic acid buffer solutions adjusted to pH 4.1, its dissolution rate was determined by chemical analysis. The eroded surface of the cement was examined by X-ray diffraction and SEM observation. The dissolution process of the cement immersed in the acetic acid buffer solution was mainly controlled by the diffusion of releasing species through the cement matrix and that of the cement immersed in the lactic acid buffer solution by the decomposition of the cement matrix at the surface. PMID- 2207237 TI - Dermal equivalents. PMID- 2207236 TI - In vivo characteristics of low molecular weight copolymers composed of L-lactic acid and various DL-hydroxy acids as biodegradable carriers for drug delivery systems. AB - Low molecular weight and amorphous copolyesters composed of 70 mol% L-lactic acid and 30 mol% DL-hydroxy acids such as DL-lactic acid, DL-alpha-hydroxy-n-butyric acid, DL-alpha-hydroxyisovaleric acid and DL-alpha-hydroxyisocaproic acid were synthesized by direct copolycondensation in the absence of catalysts, to evaluate their in vivo capabilities as biodegradable carriers for drug delivery systems. For this purpose, the copolyester was moulded into a small cylindrical specimen under melt-pressing technique and implanted subcutaneously in the back of male adult rats. The in vivo degradation pattern can be subdivided into three types: the formations of parabolic type (L-LA/DL-HBA copolymer), linear type (L-LA/DL-LA copolymer) and S type (L-LA/DL-HIVA and L-LA/DL-HICA copolymers). A luteinizing hormone-releasing hormone agonist, des-Gly10-(D-Leu6)-LH-RH ethylamide monoacetate (LH-RH agonist), was incorporated into the small cylinders of copolyester formulations, of which the strongest pharmacological influence was observed in a copoly(L-LA/DL-HICA) formulation system, resulting in the maintenance of effective pharmacological influence throughout an experimental period of 15 wk, at which the in vivo release rate of LH-RH agonist was held constant at approximately 45 micrograms/d. PMID- 2207238 TI - Long-range interactions in mammalian platelet aggregation. I. Evidence from kinetic studies in brownian diffusion. AB - The Smoluchowski theory describing aggregation in suspensions of spherical colloidal particles due to Brownian diffusion-controlled two-body collisions, was used to obtain collision efficiencies, alpha B, for adenosine diphosphate (ADP) induced platelet aggregation in citrated platelet-rich plasma (PRP) from humans, dogs, and rabbits. For these diffusion studies, PRP was stirred with 10 microM ADP for 0.5 s, then kept nonstirred at 37 degrees C for varying times before fixation; the percent aggregation was computed from the decrease in particle concentration with time measured with a resistive particle counter. Up to 20% of rabbit platelets formed microaggregates within 60 s of ADP addition to such nonstirred suspensions, corresponding to mean alpha B values of approximately 0.9. However, human and dog platelets aggregated approximately 10 times and 2-3 times faster than rabbit platelets within the first 60 s of ADP addition, corresponding to alpha B approximately 8 and 2, respectively. These high alpha B (much greater than 1) for human platelets were independent of initial platelet count and were equally observed with the calcium ionophore A23187 as activator. In about one-third of human, dog, or rabbit PRP, comparable and lower values of alpha B (less than 0.5) were obtained for a slower second phase of aggregation seen for the nonstirred PRP over 60-300 s post ADP-addition. Platelet aggregability in continually stirred PRP was distinct from that observed in Brownian diffusion (nonstirred) because comparable aggregation was observed for all three species' stirred PRP, whereas greater than 3-8 times more ADP is required to yield 50% of maximal rates of aggregation for nonstirred than for stirred PRP. The above results point to the existence of long-range interactions mediating platelet aggregation in Brownian diffusion-controlled platelet collisions which varies according to human > dog > rabbit platelets. The roles for platelet pseudopods and adhesive sites in these long-range interactions are presented in part 2. PMID- 2207239 TI - Long-range interactions in mammalian platelet aggregation. II. The role of platelet pseudopod number and length. AB - In part 1, we reported that human (H) platelets, activated with high concentrations (10 microM) of adenosine diphosphate, aggregate under Brownian diffusion (nonstirred, platelet-rich plasma) with an apparent efficiency of collision (alpha B) approximately 4 times and 8 times larger than observed, respectively, for canine (C) and rabbit (R) platelets. Further evaluations of parallel inhibition of alpha B and shape change suggested a central role for platelet pseudopods in mediating the long-range interactions associated with the elevated alpha B values. We found that greater than 90% of all platelet contacts in the doublets and triplets formed were via at least one pseudopod. We therefore compared pseudopod number and length per platelet generated by approximately 30 s post ADP activation in nonstirred PRP from human, canine, and rabbit donors, using phase-contrast, video-enhanced microscopy of fixed platelets. Theoretical calculations assessing the effects of pseudopod length and number on the collision frequency enhanced by an increased radius of a collision sphere supported the experimental observations that approximately 3 or 4 pseudopods per human or canine platelet, and approximately 5 or 6 pseudopods per rabbit platelet yield optimal alpha B values, with the average pseudopod length: approximately 3:2:1 for H/C/R, paralleling the alpha B differences. After correcting for effects of pseudopods and platelet size on platelet diffusion and sedimentation, it still appeared that the small number of long pseudopods formed on human platelets could largely explain the unusually large alpha B values. The quantitative discrepancies between theory and experiment do not appear related to time-dependent refractoriness within the less than 60 s of observation, but may be related to biochemical differences in dynamics and surface density of adhesive (sticky sites) present on the pseudopod surface. PMID- 2207240 TI - Cytoplasmic strains and strain rates in motile polymorphonuclear leukocytes. AB - A new method is presented to measure local cytoplasmic deformation and rate of deformation in motile active neutrophils. The deformation is expressed in terms of biomechanical strains and strain rates. For this purpose small phagocytosed latex microspheres were used as intracellular markers. Planar Lagrangian and Eulerian strains and the rate of strain were estimated from the positions of a triad of internalized markers. Principal strains, stretch ratios, and principal directions were computed. The intracellular strains were found to be large relative to the overall cell shape change. Principal cytoplasmic stretch ratios showed large extension in the direction of pseudopod formation and cell locomotion and contraction in perpendicular directions. Regional strain analysis showed contractile strains to predominate in the vicinity of the pseudopod or leading edge of motion. The transitional region between the pseudopod and the main cell body exhibited large shear strains. The posterior region, where the uropod is located, also revealed large extensions but small contractile strains. The rate of strains are relatively small, nonuniform in time, and largely independent of the strain. The method we propose to measure cytoplasmic strain can be applied to a variety of problems in cell mechanics. PMID- 2207241 TI - Allosteric kinetics and equilibria differ for carbon monoxide and oxygen binding to hemoglobin. AB - We have measured the forward and reverse rates of the allosteric transition between R (relaxed) and T (tense) quaternary structures for oxyhemoglobin A from which a single oxygen molecule was removed in pH 7, phosphate buffer, using the method of modulated excitation (Ferrone, F.A., and J.J. Hopfield. 1976. Proc. Natl. Acad. Sci. USA. 73:4497-4501 and Ferrone, F.A., A.J. Martino, and S. Basak. 1985. Biophys. J. 48:269-282). Despite the low quantum yield, which necessitated large light levels and an associated temperature rise, the data was of superior quality to the equivalent experiment with CO as a ligand, permitting comparison between the allosteric behavior of hemoglobin with different ligands. Qualitatively, the T structure is favored more strongly in triligated oxyhemoglobin than triligated carboxyhemoglobin. The rates for the allosteric transition with oxygen bound were essentially temperature independent, whereas for CO both the R----T and T----R rates increased with temperature, having an activation energy of 2.2 and 2.8 kcal, respectively. The R----T rate was higher for O2 than for CO being 3 x 10(3) s-1 vs. 1.6 x 10(3) s-1 for HbCO at 25 degrees C. The T----R rate for HbO2 was only 2 x 10(3) s-1, vs 4.2 x 10(3) s-1 for HbCO, giving an equilibrium constant between the structures greater than unity (L3 = 1.5). The data suggest that there may be some allosteric inequality between the subunits, but do not require (or rule out) ligand binding heterogeneity. The ligand-dependent differences are compatible with stereochemical studies of HbCO and HbO2. However,the large population of T species with three oxygen molecules bound is much greater than predicted by precision equilibrium studies and a generalized Szabo-Karplus model (Lee, A. W., M. Karplus, C. Poyart, and E. Bursaux. 1988. Biochemistry.27:1285-1301) or by the allosteric model of DiCera (Di Cera, E., C. H. Robert, and S. J. Gill. 1987. Biochemistry.26:4003-4008). PMID- 2207243 TI - Physical properties of single phospholipid bilayers adsorbed to micro glass beads. A new vesicular model system studied by 2H-nuclear magnetic resonance. AB - Spherical supported vesicles (SSVs), a new model system consisting of single dimyristoyl phosphatidylcholine (DMPC) bilayers adsorbed to spherical glass beads with a narrow size distribution, were prepared at two different sizes (0.5 and 1.5 microns) and their physical properties were studied by deuterium nuclear magnetic resonance (2H-NMR). Such SSV samples can be prepared at any desired size between 0.3 and 10 microns. The 2H-NMR measurements provide evidence for a strong dependence of the spectra and the transverse relaxation times on the curvature of the SSVs in a diameter range between 0.5 and 1.5 microns. For larger SSVs (1.5 microns diameter) their powder spectra and their calculated oriented spectra are similar to those obtained for multilamellar dispersions of DMPC-d54. The lineshape of the smaller SSVs exhibits a temperature dependence which is not found in multilamellar samples. The SSVs are stable in the liquid crystalline phase over days but irreversibly change to multilamellar vesicles in the gel state. The average thickness of the water layer between the single bilayer and the glass bead surface was estimated by 1H-NMR to e 17 +/- 5 A. PMID- 2207242 TI - Visualization of transport-related configurations of the nuclear pore transporter. AB - The transport of macromolecules between the cytoplasm and nucleus of the cell is mediated by the nuclear pore complex (NPC). In this study, details of the central transporter assembly within NPCs have been examined by cryoelectron microscopy, image processing, and classification analysis. The NPC transporter in isolated amphibian nuclei appears to adopt a minimum of four transport-related configurations including: (a) a putative closed form with a 90-100 A diameter central pore, (b) a docked form with material aligned over the pore, (c) an open form with substrates apparently caught "in transit," and (d) an open form with an enlarged pore. This data confirms previous observations on NPC transporters labeled with nucleoplasmin-gold (Akey, C.W., and D.S. Goldfarb. 1989. J. Cell Biol. 109:971-982) and allows a working model of the central NPC transporter to be proposed. The model is comprised of two supramolecular irislike assemblies which open asynchronously to provide an expanded pore for translocation while maintaining transport fidelity. PMID- 2207244 TI - Resolution of the fluorescence decay of the two tryptophan residues of lac repressor using single tryptophan mutants. AB - We have studied the time-resolved intrinsic tryptophan fluorescence of the lac repressor (a symmetric tetramer containing two tryptophan residues per monomer) and two single-tryptophan mutant repressors obtained by site-directed mutagenesis, lac W201Y and lac W220Y. These mutant repressor proteins have tyrosine substituted for tryptophan at positions 201 and 220, respectively, leaving a single tryptophan residue per monomeric subunit at position 220 for the W201Y mutant and at position 201 in the W220Y mutant. It was found that the two decay rates recovered from the analysis of the wild type data do not correspond to the rates recovered from the analysis of the decays of the mutant proteins. Each of these residues in the mutant repressors displays at least two decay rates. Global analysis of the multiwavelength data from all three proteins, however, yielded results consistent with the fluorescence decay of the wild type lac repressor corresponding simply to the weighted linear combination of the decays from the mutant proteins. The effect of ligation by the antagonistic ligands, inducer and operator DNA, was similar for all three proteins. The binding of the inducer sugar resulted in a quenching of the long-lived species, while binding by the operator decreased the lifetime of the short components. Investigation of the time-resolved anisotropy of the intrinsic tryptophan fluorescence in these three proteins revealed that the depolarization of fluorescence resulted from a fast motion and the global tumbling of the macromolecule. Results from the simultaneous global analysis of the frequency domain data sets from the three proteins revealed anisotropic rotations for the macromolecule, consistent with the known elongated shape of the repressor tetramer. In addition, it appears that the excited-state dipole of tryptophan 220 is alighed with the long axis of the repressor. PMID- 2207245 TI - Permanent dipole moment of tRNA's and variation of their structure in solution. AB - The structure of six different tRNA molecules has been analyzed in solution by electrooptical measurements and by bead model simulations. The electric dichroism measured as a function of the field strength shows that tRNA's are associated with substantial permanent dipole moments, which are in the range of 1 x 10(-27) cm(identical to 300 D; before correction for the internal directing field). Rotational diffusion time constants of tRNA molecules in their native state at 2 degrees C show a considerable variation. A particularly large value found for tRNA(Tyr) (50 ns) can be explained by its nine additional nucleotide residues. However, remarkable variations remain for tRNA molecules with the standard number of 76 nucleotide residues (tRNA(Phe) [yeast] 41.6 ns, tRNA(Val) [Escherichia coli] 44.9 ns, tRNA(Glu) [E. coli] 46.8 ns; tRNA(Phe) [E. coli] 48.3 ns). These variations indicate modulations of the tertiary structure, which may be due to a change of the L-hinge angle. Bead models are used to simulate both electric and hydrodynamic parameters of tRNA molecules according to the crystal structure of tRNA(Phe) (yeast). The asymmetric distribution of phosphate charges with respect to the center of diffusion leads, under the assumption of a constant charge reduction to 15% by ion condensation, to a theoretical dipole moment of 7.2 x 10( 28) cm, which is in reasonable agreement with the measurements. The dichroism decay curve calculated for tRNA(Phe) (yeast) is also consistent with the measurements and thus the structure in solution and in the crystal must be very similar in this case. However, our measurements also indicate that the structure of some other tRNA's in solution is different, even in cases with the same number of nucleotide residues. PMID- 2207247 TI - Conformational substates and motions in myoglobin. External influences on structure and dynamics. AB - Myoglobin, a simppe dioxygen-storage protein, is a good laboratory for the investigation of the connection between protein structure, dynamics, and function. Fourier-transform infrared spectroscopy on carbon-monoxymyoglobin (MbCO) shows three major CO bands. These bands are excellent probes for the investigation of the structure-function relationship. They have different CO binding kinetics and their CO dipoles form different angles with respect to the heme normal, implying that MbCO exists in three major conformational substates, A0, A1, and A3. The entropies and enthalpies of these substates depend on temperature above approximately 180 K and are influenced by pH, solvent, and pressure. These results suggest that even a protein as simple as Mb can assume a small number of clearly different structures that perform the same function, but with different rates. Moreover, protein structure and dynamics depend strongly on the interaction of the protein with its environment. PMID- 2207246 TI - Slow rotational mobilities of antibodies and lipids associated with substrate supported phospholipid monolayers as measured by polarized fluorescence photobleaching recovery. AB - Polarized fluorescence photobleaching recovery has been used to monitor slow rotational motions of a fluorescently-labeled anti-dinitrophenyl mouse IgGl monoclonal antibody (ANO2) specifically bound to substrate-supported monolayers composed of a mixture of distearoylphosphatidylcholine (DSPC) and dinitrophenyldioleoylphosphatidylethanolamine (DNP-DOPE). ANO2 antibodies were labeled with a new bifunctional carbocyanine fluorophore that has two amino reactive groups; steady-state fluorescence anisotropy data confirmed the expected result that the ANO2-conjugated bifunctional probe had less independent flexibility than ANO2-conjugated unifunctional fluorescence labels. Rotational mobilities were also measured for the fluorescent lipid 1,1'-dioctadecyl 3,3,3',3'-tetramethylindocarbocyanine (dil) in DSPC and in mixed DSPC/DNP-DOPE monolayers in the presence and absence of unlabeled ANO2 antibodies. The apparent rotational correlation time and fractional mobility of ANO2 on supported monolayers were approximately 70 and approximately 0.3 s, respectively. These measured parameters of rotational mobility did not depend on the ANO2 surface density or on kinetic factors, but addition of unlabeled polyclonal anti-(mouse IgG) antibodies significantly decreased the apparent mobile fraction. The measured fluorescence recovery curves for dil were consistent with two fluorophore populations with rotational correlation times of approximately 4 and approximately 100 s and a population of immobile fluorescent lipid. No difference in fluorescence recovery and decay curves was measured for dil in DSPC monolayers, DSPC/DNP-DOPE monolayers, and DSPC/DNP-DOPE monolayers treated with unlabeled ANO2 antibodies. PMID- 2207248 TI - Vibrational fluctuations of hydrogen bonds in a DNA double helix with alternating TA type inserts. AB - The Green's function technique is applied to a study of breathing modes in a DNA double helix which contains a region of different base pairs from the rest of the double helix. The calculation is performed on an alternating poly(dC-dG).poly(dC dG) helix in the B conformation with four consecutive base pairs replaced by a model of a biological promoter region with four alternating T-A,A-T base pairs, henceforth referred to as (TATA)2. The average stretch of interbase hydrogen bonds is found to be amplified around the insert. This is likely related to the (TATA)2 insert having a lower stability against hydrogen bond melting than the two semi-infinite poly(dC-dG).poly(dC-dG) helices. The insert region may be considered to be a site of enhanced tendency to melt in such a helix. The results show that an alternating AT insert of four base pairs has a larger average hydrogen bond stretch inside and outside the insert region than the average hydrogen bond stretch inside and outside an insert of four consecutive A-T base pairs, henceforth referred to as (AAAA).(TTTT). Calculations are performed which show that the enhancement of the average hydrogen bond stretch around an alternating TA type insert is greatly dependent upon the local modes and not the inband modes. The amount of local mode enhanced average stretch is explored as a function of insert size. PMID- 2207249 TI - Magnetically orientable phospholipid bilayers containing small amounts of a bile salt analogue, CHAPSO. AB - Buffered mixtures of the detergent 3-(cholamidopropyl)dimethylammonio-2-hydroxy-1 propanesulfonate (CHAPSO) and dimyristoylphosphatidylcholine (DMPC) orient in the presence of a strong magnetic field over a wide range of water contents (at least 65-85%) and CHAPSO:DMPC molar ratios (typically 1:10-1:3). 31P NMR studies show that the phospholipid in such mixtures is oriented with its director axis perpendicular to the magnetic field. 31P and 2H NMR results also suggest that the structure and dynamics of the DMPC molecules are similar to that of pure phospholipids existing in the liquid crystalline (L alpha) bilayer phase. The ability of 1:5 CHAPSO:DMPC samples to orient is highly tolerant of large changes in temperature, pH, and ionic strength, as well as to the addition of substantial amounts of charged amphiphiles or soluble protein. However, 2H NMR studies of deuterated beta-dodecyl melibiose (DD-MB) solubilized in the system indicate the head group conformation and/or dynamics of this glycolipid analogue is dependent upon the CHAPSO concentration. Despite the latter results, the orientational versatility of the system, together with the nondenaturing properties of CHAPSO, makes this system useful in spectroscopic studies of membrane-associated phenomena. PMID- 2207250 TI - Octopus photoreceptor membranes. Surface charge density and pK of the Schiff base of the pigments. AB - The chromophore of octopus rhodopsin is 11-cis retinal, linked via a protonated Schiff base to the protein backbone. Its stable photoproduct, metarhodopsin, has all-trans retinal as its chromphore. The Schiff base of acid metarhodopsin (lambda max = 510 nm) is protonated, whereas that of alkaline metarhodopsin (lambda max = 376 nm) is unprotonated. Metarhodopsin in photoreceptor membranes was titrated and the apparent pK of the Schiff base was measured at different ionic strengths. From these salt-dependent pKs the surface charge density of the octopus photoreceptor membranes and the intrinsic Schiff base pK of metarhodopsin were obtained. The surface charge density is sigma = -1.6 +/- 0.1 electronic charges per 1,000 A2. Comparison of the measured surface charge density with values from octopus rhodopsin model structures suggests that the measured value is for the extracellular surface and so the Schiff base in metarhodopsin is freely accessible to protons from the extracellular side of the membrane. The intrinsic Schiff base pK of metarhodopsin is 8.44 +/- 0.12, whereas that of rhodopsin is found to be 10.65 +/- 0.10 in 4.0 M KCl. These pK values are significantly higher than the pK value around 7.0 for a retinal Schiff base in a polar solvent; we suggest that a plausible mechanism to increase the pK of the retinal pigments is the preorganization of their chromophore-binding sites. The preorganized site stabilizes the protonated Schiff base with respect to the unprotonated one. The difference in the pK for the octopus rhodopsin compared with metarhodopsin is attributed to the relative freedom of the latter's chromophore-binding site to rearrange itself after deprotonation of the Schiff base. PMID- 2207252 TI - Muscle stiffness measured under conditions simulating natural sound production. AB - Isolated whole frog gastrocnemius muscles were electrically stimulated to peak twitch tension while held isometrically in a bath at 4 degrees C. A quartz hydrophone detected vibrations of the muscle by measuring the pressure fluctuations caused by muscle movement. A small steel collar was slipped over the belly of the muscle. Transient forces including plucks and steady sinusoidal driving were applied to the collar by causing currents to flow in a coil held near the collar. The instantaneous resonant frequencies measured by the pluck and driving techniques were the same at various times during a twitch contraction cycle. The strain produced by the plucking technique in the outermost fibers was less than 1.6 x 10(-4%), a strain three orders of magnitude less than that required to drop the tension to zero in quick-length-change experiments. Because the pressure transients recorded by the hydrophone during plucks and naturally occurring sounds were of comparable amplitude, strains in the muscle due to naturally occurring sound must also be of the order 10(-3%). A simple model assuming that the muscle is an elastic bar under tension was used to calculate the instantaneous elastic modulus E as a function of time during a twitch, given the tension and resonant frequency. The result for Emax, the peak value of E during a twitch, was typically 2.8 x 10(6) N/m2. The methods used here for measuring muscle stiffness are unusual in that the apparatus used for measuring stiffness is separate from the apparatus controlling and measuring force and length. PMID- 2207251 TI - Molecular dynamics of an in vacuo model of duplex d(CGCGAATTCGCG) in the B-form based on the amber 3.0 force field. AB - The characteristics of 100 ps of molecular dynamics (MD) on the DNA dodecamer d(CGCGAATTCGCG) at 300 K are described and investigated. The simulation is based on an in vacuo model of the oligomer and the AMBER 3.0 force field configured in the manner of Singh, U. C., S. J. Weiner, and P. A. Kollman, (1985, Proc. Natl. Acad. Sci. USA. 82:755-759). The analysis of the results was carried out using the "curves, dials, and windows" procedure (Ravishanker, G., S. Swaminathan, D. L. Beveridge, R. Lavery, and H. Sklenar. 1989. J. Biomol. Struct. Dyn. 6:669 699). The results indicate this dynamical model to be a provisionally stable double helix which lies at approximately 3.2 A rms deviation from the canonical B form. There is, however, a persistent nonplanarity in the base pair orientations which resemble that observed in canonical A-DNA. The major groove width is seen to narrow during the course of the simulation and the minor groove expands, contravariant to the alterations in groove width seen in the crystal structure of the native dodecamer (Drew, H. R., R. M. Wing, T. Takano, C. Broka, S. Tanaka, I. Itakura, and R. E. Dickerson, 1981. Proc. Natl. Acad. Sci. USA. 78:2179-2183). The propeller twist in the bases, the sequence dependence of the base pair roll and aspects of bending in the helix axis are in some degree of agreement with the crystal structure. The patterns in DNA bending are observed to follow Zhurkin theory (Zhurkin, V. B. 1985. J. Biomol. Struct. Dyn. 2:785-804.). The relationship between the dynamical model and structure in solution is discussed. PMID- 2207254 TI - Effects of tetrodotoxin on heart cell aggregates. Phase resetting and annihilation of activity. AB - The influence of relatively low concentrations of tetrodotoxin (TTX) on phase resetting of spontaneous activity of embryonic chick atrial heart cell aggregates by brief duration current pulses was investigated experimentally and theoretically. The maximal upstroke velocity, Vmax, of the spontaneous action potential was reduced by TTX in a concentration-dependent manner for [TTX] less than 10(-7) M. However, the beat rate was unaffected in this concentration range. Application of a depolarizing current pulse of brief duration during a critical region of the spontaneous cycle annihilated activity in some preparations exposed to [TTX] approximately 10(-7) M. These results were analyzed with the model of electrical activity described in the previous paper (Clay, J.R., R.M. Brochu, and A. Shrier. 1990. Biophys. J. 58:609-621) based on a tonic block of the INa channel by TTX with a dissociation constant, KD, of 50 nM. PMID- 2207253 TI - Phase resetting of embryonic chick atrial heart cell aggregates. Experiment and theory. AB - The influence of brief duration current pulses on the spontaneous electrical activity of embryonic chick atrial heart cell aggregates was investigated experimentally and theoretically. A pulse could either delay or advance the time of the action potential subsequent to the pulse depending upon the time in the control cycle at which it was applied. The perturbed cycle length throughout the transition from delay to advance was a continuous function of the time of the pulse for small pulse amplitudes, but was discontinuous for larger pulse amplitudes. Similar results were obtained using a model of the ionic currents which underlie spontaneous activity in these preparations. The primary ion current components which contribute to phase resetting are the fast inward sodium ion current, INa, and the primary, potassium ion repolarization current, IX1. The origin of the discontinuity in phase resetting of the model can be elucidated by a detailed examination of the current-voltage trajectories in the region of the phase response curve where the discontinuity occurs. PMID- 2207255 TI - Exact solution of a model of diffusion in an infinite chain or monolayer of cells coupled by gap junctions. AB - Analytic solutions are found for an infinite chain of cells coupled by gap junctions under two initial conditions: (a) One inner cell initially filled uniformly to a fixed concentration and (b) inner cell maintained indefinitely at constant concentration. The solution can be extended by the product method (Carslaw and Jaeger. 1959. Conduction of Heat in Solids. Oxford University Press.) to monolayers. We can also incorporate leakage through the plasma membrane by the product method. We demonstrate the utility of these results by fitting diffusion data from the septate axon of earthworm and by plots of theoretical profiles from monolayers of cells. Use of these analytic solutions enables one to overcome the limitations of methods that lump the effects of cytoplasmic diffusion and junctional permeability into an effective diffusion coefficient. PMID- 2207256 TI - Cell-cell conjugation. Transient analysis and experimental implications. AB - In the present study we investigate the transient conjugation of cell pairs by using a mathematical model. Macromolecules responsible for adhesion (bonds) are assumed to exist in two reversible states, attached and unattached, and exert a force elastic in nature only when they cross-link the two cell surfaces (attached state). Bonds form a link between the two cell surfaces only in the attached form. The unattached bridges are assumed laterally mobile in the plane of the cell membrane. Lateral mobility of attached bonds may be limited by structures on the undersurface of the cell membrane. Using this model we show that the bond density distribution between a cytotoxic T-cell (F-1) and a cancer cell (JY:HLA A2-B7-DR4, W6) approaches equilibrium within 10 min, the incubation period used in experiments by Sung, K.L.P., L.A. Sung, M. Crimmins, S.J. Burakoff, and S. Chien (1986. Science [Wash. DC]. 234:1405-1408). If the diffusion coefficient of attached bonds is set equal to zero in the computations the model predictions indicate accumulation of bonds at the edge of conjugation. This prediction is consistent with present experimental data on lectin-induced red blood cell aggregation (Vayo, M., R. Skalak, P. Brunn, S. Usami, and S. Chien. 1987. Fed. Proc. 46:1043). It is concluded that significant features of micromanipulation data on specific adhesion can be explained by the diffusivity properties of bonds responsible for adhesion. PMID- 2207257 TI - Resonance energy transfer from a cylindrical distribution of donors to a plane of acceptors. Location of apo-B100 protein on the human low-density lipoprotein particle. AB - The resonance energy transfer (RET) from a cylindrical assembly of donors to acceptors in a plane was investigated, and the dependence the average RET rate (kT) on the cylinder's size, shape, and proximity to the acceptor plane was determined. This geometry provides a model for the RET from a donor-containing protein to acceptors embedded in an associated phospholipid mono- or bilayer. The determination of kT for a series of acceptors at different levels in the phospholipid layer is shown to provide information on the protein's relationship to the phospholipid layer. Two models for the donor (D) and acceptor (A) distributions are employed: (a) The D's and A's are uniformly distributed in the cylinder and the plane, respectively, and analytical expressions for kT in terms of experimental parameters are derived. (b) The RET rates between all D, A pairs within the cylinder and in the plane are calculated and averaged for a large number of random D and A distributions. The average transfer rates obtained by the two approaches are in agreement and the width of the frequency distribution of kT for the latter provides an estimate of the error to be expected when, as is usually the case, the true D and A locations are unknown. This methodology is illustrated by analyzing RET from the 37 tryptophan residues of the apo-B100 protein to a series of pyrenylphosphatidylcholine acceptors inserted in the phospholipid monolayer of the human low-density lipoprotein particle, and it is concluded that significant portions of the protein penetrate the phospholipid layer. PMID- 2207259 TI - Theoretical description of the spatial dependence of sickle hemoglobin polymerization. AB - We have generalized the double nucleation mechanism of Ferrone et al. (Ferrone, F. A., J. Hofrichter, H. Sunshine, and W. A. Eaton. 1980. Biophys. J. 32:361-377; Ferrone, F. A., J. Hofrichter, and W. A. Eaton. 1985. J. Mol. Biol. 183:611-631) to describe the spatial dependence of the radial growth of polymer domains of sickle hemoglobin. Although this extended model requires the consideration of effects such as monomer diffusion, which are irrelevant to a spatially uniform description, no new adjustable parameters are required because diffusion constants are known independently. We find that monomer diffusion into the growing domain can keep the net unpolymerized monomer concentration approximately constant, and in that limit we present an analytic solution of the model. The model shows the features reported by Basak, S., F. A. Ferrone, and J. T. Wang (1988. Biophys J. 54:829-843) and provides a new means of determining the rate of polymer growth. When spatially integrated, the model exhibits the exponential growth seen in previous studies, although molecular parameters derived from analysis of the kinetics assuming uniformity must be modified in some cases to account for the spatially nonuniform growth. The model developed here can be easily adapted to any spatially dependent polymerization process. PMID- 2207258 TI - Kinetics of the premelting (L beta'-P beta') and main transition (P beta'-L alpha) in hydrated dipalmitoylphosphatidylcholine. A time-resolved x-ray diffraction study using microwave-induced temperature-jumps. AB - The dynamics and mechanism of the premelting (L beta'-P beta') and main transitions (P beta'-L alpha) in fully hydrated dipalmitoylphosphatidylcholine were examined by low-angle time-resolved x-ray diffraction (TRXRD) using microwave radiation to effect uniform, internal sample heating. Equilibrium and dynamic aspects of the transitions were investigated. The dynamic studies involved applying a temperature jump of sufficient amplitude to effect the two transitions sequentially. Our findings are as follows. (a) Microwave radiation has proven useful as a means for implementing rapid and uniform internal heating in temperature-jump studies of lipid-phase transition kinetics. (b) Heating rate can be controlled by adjusting microwave power setting. (c) The thermal expansion coefficient of the three lyotropic phases follows the sequence L beta' not equal to O greater than P beta' much greater than L alpha. (d) Regardless of temperature-jump amplitude and sample heating rate the P beta' phase was always in evidence as an intermediate between the L beta' and L alpha phases. (e) The degree of development of the P beta' phase was inversely proportional to temperature-jump amplitude and heating rate. (f) The shortest transit time recorded for the combined L beta'-P beta', and P beta'-L alpha transitions was less than 1 s. (g) Upon cooling from the L alpha phase the onset of the chain disorder/order transition was apparent as a dramatic change of slope in the scattering angle vs. time plot which is interpreted as arising from sample heating by the latent heat of the transition. (h) Based on the shape of the low angle diffraction pattern of the P beta' phase the P beta'-L alpha transition appears to be reversible with no evidence of metastability as was observed in the slow scan TRXRD measurements of Tenchov et al. (1989. Biophys. J. 56:757-768). PMID- 2207260 TI - Cross-correlated photon scattering during the photocycle of bacteriorhodopsin. AB - Changes in the ultraviolet light scattering from a suspension of purple membrane fragments were detected during the photocycle of bacteriorhodopsin with a cross correlation method. The scattered light intensity from a suspension of membrane fragments containing the protein bacteriorhodopsin was measured on a logarithmic time scale of 1 microsecond to 0.1 s at pH 4.6 after the photocycle was initiated with a polarized 532-nm laser flash. A simple model of curved sheets with positive and negative changes in the curvature is used to describe the observed light scattering changes. A detailed mathematical derivation of the model as well as the pictorial description are given. The changes in curvature of the membrane fragment are more than likely driven by the protein during the photocycle and are observed to have at least two time-resolved components, each changing the curvature of the fragment with an opposite sign. PMID- 2207262 TI - A polymorphism peculiar to bipolar actin bundles. AB - Both muscle and nonmuscle actins produced magnesium paracrystals which we found indistinguishable from one another. Contrary to some previous reports, calcium ions caused no change in filament organization for either type of actin. The most ordered paracrystals consisted of hexagonally packed filaments with opposite polarities. We suggest that this mode of packing permits a form of disorder not previously described, which may account for some puzzling aspects of earlier observations and may prove useful in analyzing actin bundles formed, for example, with erythrocyte band 4.9 protein. PMID- 2207261 TI - Small angle neutron scattering studies of HbA in concentrated solutions. AB - Differential cross-sections for neutrons scattered by normal human hemoglobin have been determined over the range of concentrations from 2 to approximately 35 weight percent. Data are compared with structure factors calculated from models of monodisperse hard spheres interacting through a screened Coulomb potential. Good agreement is noted when the volume fraction eta is adjusted during multivariate fitting of data, but the fitted value of eta is always lower than expected from the known Hb concentration of the samples. Calculations of cross sections for polydisperse scatterers suggest that the samples may contain oligomers of the fundamental tetrameric Hb molecule. PMID- 2207263 TI - Mixing behavior of identical molecular weight phosphatidylcholines with various chain-length differences in two-component lamellae. AB - It has recently been suggested that mixed-chain phosphatidylcholines with normalized chain length differences (deltaC/CL) in the range of 0.10-0.40 undergo spontaneous self-assembly in excess water at T less than Tm into the partially interdigitated bilayer and those with delta C/CL values in the range of 0.44-0.57 form, in excess water, mixed interdigitated bilayers at T less than Tm. The mixing behavior of binary mixtures of C(22):C(12)PC/C(17):C(17)PC, C(22):C(12)/C(15):C(19)PC, and C(15):C(19)PC/C(13):C(21)PC reported in this work is used to support this view. The values of delta C/CL for C(17):C(17)PC, C(15):C(19)PC, C(13):C(21)PC, and C(22):C(12)PC are 0.10, 0.15, 0.35, and 0.55, respectively. The binary mixture of C(15):C(19)PC/C(13):C(21)PC exhibits a lens shaped phase diagram, indicating that these two identical molecular weight (MW) lipids with delta C/CL values less than 0.4 are completely miscible over the entire compositional range in both gel and liquid-crystalline phases. In contrast, the phase diagrams of C(22):C(12)PC/C(17):C(17)PC and C(22):C(12)PC/C(15):C(19)PC are eutectic, indicating immiscibility of the component lipids over a wide compositional range in the gel phase. This immiscibility of identical MW lipids in the bilayer plane can be attributed to the different packing properties of the component lipids in the bilayer at T less than Tm. PMID- 2207264 TI - Early regulation of membrane excitability by ras oncogene proteins. AB - Two electrode voltage clamp conditions were used to study the early effects on ionic membrane channels of the intracellularly injected proto-oncogenic form of c Ha-ras (c-ras) and its oncogenic counterpart v-Ha-ras (v-ras). These experiments were conducted on isolated somata of identified fully differentiated neurons of the sea snail Hermissenda. 20 min after c-ras, and 10 min after v-ras intracellular injections into type B medial photoreceptors of Hermissenda, the peak amplitude of two outward potassium currents (IA and IC), across the isolated Type B soma membrane begin to decrease. These two currents have been previously isolated by differences in activation and inactivation kinetics and their response to pharmacological blockers. c- or v-ras injections did not have any effect on a voltage-dependent inward calcium current. Reduction of IA preceded that of IC. Current reductions due to c-ras, but not to v-ras injection reversed spontaneously after 40 min. The voltage dependence of the steady state inactivation of IA shifted toward more negative potentials with ras injections. Ras-mediated cell transformations therefore, could involve, perhaps as initial events, prolonged modification of membrane currents. PMID- 2207265 TI - A novel action of isoproterenol to inactivate a cardiac K+ current is not blocked by beta and alpha adrenergic blockers. AB - The K+ current iKl sets the resting potential in cardiac cells. Here we report that isoproterenol (ISO), a prototypical beta agonist, increases inactivation of iKl. This action of ISO on iKl is mimicked by permeant analogues of cAMP but is not blocked by the beta blockers propranolol and pindolol or the alpha blockers prazosin or yohimbine. We suggest that this novel action of ISO may contribute to pacemaker activity in the Purkinje strand and be mediated through a class of receptors different from classical beta's or alpha's. PMID- 2207266 TI - IK inactivation in squid axons is shifted along the voltage axis by changes in the intracellular pH. AB - The inactivation curve of the delayed rectifier in internally perfused squid giant axons is shifted along the voltage axis by changes in the pH of the internal perfusate. The amplitude of the shift is 9.5 mV per pH unit (6 less than or equal to pHi less than or equal to 10). No saturation of the effect was observed at either end of the pH range. This result suggests that the inactivation gating mechanism has several titratable groups accessible to protons from the intracellular side of the membrane. PMID- 2207267 TI - Analysis of the nucleation and crystal growth kinetics of lysozyme by a theory of self-assembly. AB - Concentration changes in supersaturated solutions during the nucleation and growth of the orthorhombic form of hen egg-white lysozyme crystals have been observed for 121 d at 35 degrees C and pH 4.6, and with 3% NaCl. The effect of a variation in the initial protein concentration on the rate of approach to solubility in equilibrium is analyzed, by applying a model, originally developed for the understanding of protein self-assembly. It is shown that the observed kinetics can be explained fairly well by this model, whose basic assumptions are that (a) the nucleation is induced by aggregation of i0 molecules into particular geometry, and (b) the growth proceeds via attachment of a monomer. The i0 value for this process is four, which agrees with the number of molecules in a unit cell. Similarity and dissimilarity of the observed crystal growth to that of low molecular weight substances are discussed. PMID- 2207268 TI - Calculation of site affinity constants and cooperativity coefficients for binding of ligands and/or protons to macromolecules. I. Generation of partition functions and mass balance equations. AB - The thermodynamics of binding of a ligand A and/or proton H to a macromolecule M is treated by the partition function method. In complex systems, the representation of the equilibria by means of cumulative constants beta PQR used as coefficients in partition functions ZM, ZA, and ZH is ill-suited to least squares refinement procedures because the cumulative constants are interrelated by common cooperativity functions gamma j(i) and common site affinity constants kappa j. There is therefore the need to express ZM, ZA, ZH as functions of site constants kappa j and cooperativity coefficients bj. This is done by developing an algebra of partition functions based on the following concepts: (i) factorability of partition functions; (ii) binary generating function Jj = (1 + kappa j[Y])i tau for each class j of sites, represented by column (Jj) and row (Jj) vectors; (iii) cooperativity between sites of one class described by functions gamma j(i), represented by diagonal matrices gamma j; (iv) probability of finding microspecies represented by elements of tensor product matrix Ll = (J1)[J2]; (v) statistical factors mij obtained from Newton polynomials, Jj; (vi) power operators Oi', O(i-l)', and O(i tau-l)', transforming vectors Jj; and (vii) operators Oi or O(i-l) indicating tensor products of i or (i-l) vectors Jj. Vectors Jj combined in tensors Ll give rise to both an affinity/cooperativity space and a parallel index space. The partition functions ZM, ZA, and ZH and the total amounts TM, TA, and TH can be obtained as an appropriate sum of elements of matrices Ll, each of which is represented in an index space by a combination p1, p2,...q1, q2,...r1, r2,... of indices ij. From these indices the contribution of that element to partition function ZM, ZA, or ZH and to total amount TM, TA, or TH is calculated in the affinity/cooperativity space as product of factors: [i tau !/i !(i tau-i)!]kappa ij(exp[bj (i-1)i])[X]i, i being any index p, q, r and X any component M, A, or H. Future applications of this algorithm to practical problems of macromolecule-ligand-proton equilibria are outlined. PMID- 2207269 TI - Calculation of site affinity constants and cooperativity coefficients for binding of ligands and/or protons to macromolecules. II. Relationships between chemical model and partition function algorithm. AB - The relationships between the chemical properties of a system and the partition function algorithm as applied to the description of multiple equilibria in solution are explained. The partition functions ZM, ZA, and ZH are obtained from powers of the binary generating functions Jj = (1 + kappa j gamma j,i[Y])i tau j, where i tau j = p tau j, q tau j, or r tau j represent the maximum number of sites in sites in class j, for Y = M, A, or H, respectively. Each term of the generating function can be considered an element (ij) of a vector Jj and each power of the cooperativity factor gamma ij,i can be considered an element of a diagonal cooperativity matrix gamma j. The vectors Jj are combined in tensor product matrices L tau = (J1) [J2]...[Jj]..., thus representing different receptor-ligand combinations. The partition functions are obtained by summing elements of the tensor matrices. The relationship of the partition functions with the total chemical amounts TM, TA, and TH has been found. The aim is to describe the total chemical amounts TM, TA, and TH as functions of the site affinity constants kappa j and cooperativity coefficients bj. The total amounts are calculated from the sum of elements of tensor matrices Ll. Each set of indices (pj..., qj..., rj...) represents one element of a tensor matrix L tau and defines each term of the summation. Each term corresponds to the concentration of a chemical microspecies. The distinction between microspecies MpjAqjHrj with ligands bound on specific sites and macrospecies MpAqHR corresponding to a chemical stoichiometric composition is shown. The translation of the properties of chemical model schemes into the algorithms for the generation of partition functions is illustrated with reference to a series of examples of gradually increasing complexity. The equilibria examined concern: (1) a unique class of sites; (2) the protonation of a base with two classes of sites; (3) the simultaneous binding of ligand A and proton H to a macromolecule or receptor M with four classes of sites; and (4) the binding to a macromolecule M of ligand A which is in turn a receptor for proton H. With reference to a specific example, it is shown how a computer program for least-squares refinement of variables kappa j and bj can be organized. The chemical model from the free components M, A, and H to the saturated macrospecies MpAQHR, with possible complex macrospecies MpAq and AHR, is defined first.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2207270 TI - Light-induced membrane protein phosphorylation in the bovine rod outer segment. A magic angle spinning 31P-NMR study. AB - Magic angle spinning 31P-NMR (MAS 31P-NMR) spectra of bovine rod outer segments, unphosphorylated and phosphorylated, were obtained. In the phosphorylated samples the spectra showed new resonances not assignable to phospholipids. These signals were present only when stimulation of receptor phosphorylation occurred. These resonances were not due to exogenous, soluble phosphorus-containing compounds. Limited proteolysis to remove the carboxyl-terminal region of the photoreceptor that contains the phosphorylation sites removed these resonances. The chemical shifts were in the usual range for serine phosphate and threonine phosphate. The pKa obtained from a pH titration of the 31P chemical shift was typical of serine phosphate. Therefore, these 31P-NMR resonances were assigned to the phosphorylation sites on membrane proteins in the rod outer segment disk membranes. Static 31P-NMR measurements revealed that at least some of these sites gave rise to relatively narrow resonances, indicative of considerable motional freedom of the carboxyl-terminal segment of the photoreceptor when phosphorylated. These data indicate that it is possible to study phosphorylation sites on membrane proteins using MAS 31P-NMR, and that using in vivo 31P 'spin labelling' one can study directly and selectively regions of receptors crucial to receptor function. PMID- 2207271 TI - Hydration-dependent conformational states of hemoglobin. Equilibrium and kinetic behavior. AB - The equilibrium and kinetics of methemoglobin conversion to hemichrome induced by dehydration were investigated by visible absorption spectroscopy. Below about 0.20 g water per g hemoglobin only hemichrome was present in the sample; above this value, an increasing proportion of methemoglobin appeared with the increase in hydration. The transition between the two derivatives showed a time-dependent biphasic behavior and was observed to be reversible. The rates obtained for the transition of methemoglobin to hemichrome were 0.31 and 1.93 min-1 and for hemichrome to methemoglobin 0.05 and 0.47 min-1. We suggest that hemichrome is a reversible conformational state of hemoglobin and that the two rates observed for the transition between the two derivatives reflect the alpha- and beta-chains of hemoglobin. PMID- 2207272 TI - A time-resolved fluorescence study of human copper-zinc superoxide dismutase. AB - The intrinsic fluorescence decay of human Cu,Zn superoxide dismutase was measured by frequency-domain techniques. The protein consists of two subunits, each containing one tryptophan and no tyrosine residues. Using a synchrotron radiation source, which allows facile selection of the excitation wavelength, the dependence of the emission decay upon excitation was studied. No significant excitation wavelength effects were found. The two tryptophans contained in the dimer, although fully equivalent and exposed to solvent, showed a fluorescence decay that cannot be described by a single lifetime. Either two lifetimes, or one Lorentzian-shaped continuous distribution of lifetimes, are needed to obtain a good fit. Under identical experimental conditions, control experiments showed that N-acetyltryptophanamide, an analogue of tryptophanyl residues in proteins, decays with a single lifetime. The heterogeneous decay of tryptophan fluorescence in superoxide dismutase is interpreted as due to the presence of static and/or dynamic conformers in the protein that decay with different lifetimes. The two models of discrete lifetimes and continuous distribution of lifetimes are discussed with reference to measurements on holo- and apo-human superoxide dismutase. PMID- 2207273 TI - A theoretical approach to describe monolayer-liposome lipid interaction. AB - It is known from several studies on the interaction between membrane models that mechanisms such as fusion or lipid exchange can play an important role in the process of internalization by cells of lipid vesicles and also in the physical stability of liposomes. In this paper it is shown that a simple monolayer liposome model can be used to simulate experimentally observed interactions between lipid vesicles and cell surfaces. From experimental data, a simple theoretical model is formulated to interpret the variation with time of surface pressure as a function of liposome concentration. The congruency of the physico chemical hypothesis and its validity are studied and correlated with results from experimental systems. PMID- 2207274 TI - Influence of the solvent on the conformational-dependent properties of random coil polypeptides. I. The mean-square of the end-to-end distance and of the dipole moment. AB - Conformational energies for the N-acetyl-N'-methylamides of the 20 natural amino acids were calculated, including the solvent effects, as functions of the angles phi and psi for rotation of the main chain and for six positions chi 1 of the C alpha-C beta bond in the side chain (fixed values for chi 2, chi 3, ...). The computed energies were used to evaluate the mean-square end-to-end distance and mean-square dipole moment of homopolypeptides of the 20 natural amino acids. Ten proteins and three enzymes of current interest were also studied. Slight differences in both properties are found on taking the effects of solvent into consideration. Comparison with other computational and experimental results is made. PMID- 2207275 TI - 1H-NMR studies on the self-association of chloroquine in aqueous solution. AB - The concentration dependences of 1H-NMR chemical shifts and spin-lattice relaxation rates were measured for chloroquine in aqueous solution. The weak self association constant was evaluated according to a dimerization equilibrium with the formation of self-stacked adducts (Kd = 4.52 +/- 0.68 l mol-1). The motional correlation times were evaluated for the monomer and the dimer by measuring intramolecular dipolar cross-relaxation rates of aromatic vicinal protons (tau cm = 0.06 ns and tau cd = 0.26 ns). The geometry of the stacked dimer was elucidated by measuring intermolecular dipolar cross-relaxation rates and interpreted in terms of partial superposition of quinoline moieties. PMID- 2207276 TI - Modulation of egg-white lysozyme activity by viscosity intensifier additives. AB - The activity of egg-white lysozyme was measured in the presence of carbohydrate additives in the reaction medium. These additives show a significant affinity for water. They depress water activity and increase the viscosity of the medium. Solute-solvent interactions in aqueous solutions of the additives are characterized by properties such as the intrinsic viscosity, Huggins constant apparent molar volume and hydration number. It was found that, despite the lowering of enzyme activity when the concentration of additive is increased, the behavior remains Michaelian and neither modification of Km nor inhibition by excess substrate is observed. On the other hand, the effect of the viscosity of the medium on enzyme activity was determined. This effect is independent of the nature of the additive at high viscosities (greater than 4 mPa s-1) for which enzyme activity is very low and appears to vary according to the kind of additive in dilute solution at low viscosities (less than 2 mPa s-1). PMID- 2207277 TI - The linkage between adenosine nucleotide binding and amidase activity in human alpha-thrombin. AB - The amidase activity of human alpha-thrombin has been studied in the presence of the adenosine nucleotides AMP, ADP and ATP. At low concentrations, adenosine nucleotides increase thrombin activity up to 30%, while at high concentrations (greater than 5 mM) inhibition takes place up to 20%. Inhibition is progressively reduced by increasing substrate concentration. A simple, phenomenological description of the linkage between adenosine nucleotide binding and amidase activity of human alpha-thrombin is proposed and the free energy changes for the underlying reactions involved in the linkage scheme are resolved by global analysis of the experimental data. The linkage scheme assumes that thrombin activation is determined by a conformational transition due to binding of adenosine nucleotides to a regulatory site. Inhibition, on the other hand, would be a consequence of competitive binding to the catalytic site. PMID- 2207278 TI - Porphyrin intercalation and non-specific 'edge on' outside binding to natural DNA. AB - A theoretical two-mode binding model for porphyrin binding to natural DNA is presented. One of the binding modes is assumed to be base sequence specific with binding sites n base-pairs long. The other binding mode has binding sites which consist of only one base-pair and can involve cooperativity. The model fits satisfactorily to data for H2TMPyP-4, Cu(II)TMPyP-3 and Cu(II)TMPyP-4 binding to calf thymus DNA in both a high (mu congruent to 1.0 M) and a low (mu congruent to 0.2 M) ionic strength buffer. The results show that the fraction of porphyrin bound in the non-specific mode reaches a maximum at certain input DNA to porphyrin concentrations ratios. The value of this maximum decreased, and its position shifted to higher DNA to porphyrin concentration ratios for binding in the high ionic strength buffer. The value of the cooperativity parameter obtained through the fitting process suggests that the non-specific binding is positively cooperative. The results are compared with the data analysed using other techniques. PMID- 2207279 TI - Molecular structure of tetanus neurotoxin as revealed by Fourier transform infrared and circular dichroic spectroscopy. AB - Secondary structure contents of tetanus neurotoxin have been estimated at neutral and acidic pH using circular dichroism (CD) and Fourier transform infrared (FT IR) spectroscopy. An analysis of the far-ultraviolet CD spectra of the neurotoxin dissolved in 50 mM citrate-phosphate buffer (pH 7.0) revealed 20.0 +/- 2.1% alpha helix, 50.5 +/- 2.1% beta-pleated sheets, no beta-turns, and 29.5% random coils, which is at considerable variance with results from an earlier detailed study of tetanus neurotoxin's secondary structures (J.P. Robinson, L.A. Holladay, J.H. Hash and D. Puett, J. Biol. Chem. 257 (1982) 407). However, the alpha-helix content estimated in this study is consistent with the earlier studies of Robinson et al. (J.P. Robinson, L.A. Holladay, J.B. Picklesimer and D. Puett, Mol. Cell. Biochem. 5 (1974) 147; J.P. Robinson, J.B. Picklesimer and D. Puett, J. Biol. Chem. 250 (1975) 7435) and with the study by Lazarovici et al. (P. Lazarovici, P. Yanai and E. Yavin, J. Biol. Chem. 262 (1986) 2645), although other secondary structural features do not agree with those of the previous studies. Secondary structure estimation from Fourier transform infrared spectra in both amide I and amide III frequency regions revealed 22-23% alpha-helix, 49 51% beta-pleated sheets and 27-28% random coils, indicating a good correlation with the secondary structure content estimated from CD analysis. Lowering of the pH of the neurotoxin to 5.5 or 4.0 did not result in any noticeable change in the overall secondary structures. However, there were significant pH-induced variations observed in the individual curve-fitted FT-IR bands in the amide III frequency region. For example, the 1302 cm-1 band (relative area, 4.2%) observed at pH 7.0 was shifted to 1297 cm-1 (relative area, 2.2%) at pH 5.5, and the relative area of the band at 1316-1317 cm-1 (alpha-helix) increased by approx. 40%. This study suggests that contrary to earlier reports, tetanus neurotoxin is a beta-pleated sheet dominated structure, and although lower pH does not change the overall contents of the secondary structures, significant conformational alterations are observed. PMID- 2207280 TI - Conformational distributions of melittin in water/methanol mixtures from frequency-domain measurements of nonradiative energy transfer. AB - We used fluorescence energy transfer to examine the effects of solvent composition on the distribution of distances between the single tryptophan residue of melittin (residue 19) to the N-terminal alpha-amino group, which was labeled with a dansyl residue. The tryptophan intensity decays, with and without the dansyl acceptor, were measured by the frequency-domain method. The data were analyzed by a least-squares algorithm which accounts for correlation between the parameters. A wide distribution of tryptophan to dansyl distances was found for the random-coil state, with a Gaussian half-width of 25 A. Increasing concentrations of methanol, which were shown to induce and alpha-helical conformation, resulted in a progressive decrease in the width of the distribution, reaching a limiting half-width of 3 A at 80% (v/v) methanol. The distance from the indole moiety of Trp-19 to the dansyl group in 80% (v/v) methanol/water was found to be 25 A, as assessed from the center of the distance distribution. A distance of 24-25 A was recovered from the X-ray crystal structure of the tetramer, which is largely alpha-helical. At low ionic strength (less than 0.01) the CD spectra revealed a small fraction or amount of alpha helix for melittin in water, which implies a small fraction of residual structure. This residual structure is apparently lost in guanidine hydrochloride as demonstrated by a further broadening in the distribution of distances. These results demonstrate the usefulness of frequency-domain measurements of resonance transfer for resolution of conformational distributions of proteins. PMID- 2207281 TI - Distinct gelation mechanism between linear and branched (1--3)- beta-D-glucans as revealed by high resolution solid state 13C NMR. AB - We have recorded high-resolution 13C-NMR spectra of linear (curdlan) and branched (lentinan, HA-beta-glucan and its polyol and aldehyde derivatives) (1----3)-beta D-glucans in hydrate and gel states, in order to gain insight into their gelation mechanism. Network structure of curdlan turned out to be highly heterogeneous from its motional state, from liquid-like, through intermediate, to solid-like domains. They are studied by a variety of experiments, conventional high resolution NMR by broad-band decoupling, high-power decoupling with magic angle spinning (MAS), and cross-polarization-magic-angle-spinning (CP-MAS). Nevertheless, we found that conformations of these distinct liquid-like and solid like domains exhibit an identical single helix conformation with a small proportion of a triple helix form, supporting our previous view as to the gelation mechanism. In contrast, the network structure of branched (1----3)-beta D-glucans in the gel state arises mainly from the triple helix conformation. This means that gelation of branched (1----3)-beta-D-glucan proceeds from partial association of the triple helical chains, previously proposed for gelation of a linear glucan. Furthermore, we found that conversion from the single chain to the single helix was not achieved readily by hydration of over 8 h at 96% R.H. for branched glucan but the triple helix form is obtained when these samples are hydrated fully as in gel state. PMID- 2207282 TI - Differential scanning calorimetry studies of the inverse temperature transition of the polypentapeptide of elastin and its analogues. AB - Differential scanning calorimetry studies have been carried out on the sequential polypeptide of elastin, (L-Val1-L-Pro2-Gly3-L-Val4-Gly5)n, abbreviated as PPP, and its more hydrophobic analogues (L-Leu1-L-Pro2-Gly3-L-Val4-Gly5)n, referred to as Leu1-PPP, and (L-Ile1-L-Pro2-Gly3-L-Val4-Gly5)n, referred to as Ile1-PPP Consistent with inverse temperature transitions, the temperatures of the transitions for which maximum heat absorption occurs are inversely proportional to the hydrophobicities of the polypentapeptides (31 degrees C for PPP, 16 degrees C for Leu1-PPP, and 12 degrees C for Ile1-PPP), and the endothermic heats of the transitions are small and increase with increasing hydrophobicity, i.e., 1.2, 2.9, and 3.0 kcal/mol pentamer for PPP, Leu1-PPP, and Ile1-PPP, respectively. Previous physical characterizations of the polypentapeptides have demonstrated the occurrence of an inverse temperature transition since increase in order, as the temperature is raised above that of the transition, has been repeatedly observed using different physical characterizations. Furthermore, the studies demonstrated identical conformations for PPP and Il21-PPP above and below the transition. Both heats and temperatures of the transitions vary with hydrophobicity, but not in simple proportionality. PMID- 2207283 TI - Analysis of melting transitions of the DNA hairpins formed from the oligomer sequences d[GGATAC(X)4GTATCC] (X = A, T, G, C). AB - Optical melting transitions of the short DNA hairpins formed from the self complementary DNA oligomers d[GGATACX4GTATCC] where X = A, T, G, or C measured in 100 mM NaCl are presented. A significant dependence of the melting transitions on loop sequence is observed and transition temperatures, tm, of the hairpins vary from 58.3 degrees C for the T4 loop hairpin to 55.3 degrees C for the A4 loop. A nearest-neighbor sequence-dependent theoretical algorithm for calculating melting curves of DNA hairpins is presented and employed to analyze the experimental melting transitions. Experimental melting curves were fit by adjustment of a single theoretical parameter, Fend(n), the weighting function for a hairpin loop comprised of n single-strand bases. Empirically determined values of Fend(n) provide an evaluation of the free-energy of hairpin loop formation and stability. Effects of heterogeneous nearest-neighbor sequence interactions in the duplex stem on hairpin loop formation were investigated by evaluating Fend(n) in individual fitting procedures using two of the published sets of nearest-neighbor stacking interactions in DNA evaluated in 100 mM NaCl and given by Wartell and Benight, 1985. In all cases, evaluated values of Fend(n) were obtained that provided exact theoretical predictions of the experimental transitions. Results of the evaluations indicate: (1) Evaluated free-energies of hairpin loop formation are only slightly dependent on loop sequences examined. At the transition temperature, Tm, the free-energy of forming a loop of four bases is approximately equal for T4, G4, or C4 loops and varies from 3.9 to 4.8 kcal/mole depending on the set of nearest-neighbor interactions employed in the evaluations. This result suggests, in light of the observed differences in stability between the T4, G4, and C4 loop hairpins, that sequence-dependent interactions between base residues of the loop are most likely not the source of the enhanced stability of a T4 loop.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2207284 TI - Statistical descriptors for the size and shape of globular proteins. AB - The atomic structures of proteins epitomize the ideas of complexity and irregularity in three-dimensional objects. For such objects, size and shape are difficult to quantify, and therefore the development of unbiased parameters for these properties could facilitate their description. Statistical analysis of the frequency distribution of interatomic distances in protein structures of different classes has revealed two numerical descriptors that correlate with physicochemical properties of these macromolecules. The median (mu) of the distribution correlates (r greater than .98, n = 45) with variables indicative of size (e.g., molecular weight and radius of gyration). The exponent of the Box-Cox transformation lambda, used for converting this distribution into a symmetrical one, correlated (r = .75, n = 43) with a general dimensionless shape parameter defined as the combination of the shape-related accessible surface (A0s), molecular volume (V), and radius of gyration (Rg) in the form s = (A0sRg/V). It is suggested that for globular proteins lambda is a function of both the shape parameter s and the fractal dimension D of the protein surface. These objective descriptors of size and shape could be useful to describe other complex objects. PMID- 2207285 TI - Determining minimum energy conformations of polypeptides by dynamic programming. AB - A combinatorial optimization approach is used for solving the multiple-minima problem when determining the low-energy conformations of short polypeptides. Each residue is represented by a finite number of discrete states corresponding to single residue local minima of the energy function. These precomputed values constitute a search table and define the conformational space for discrete minimization by a generalized dynamic programming algorithm that significantly limits the number of intermediate conformations to be generated during the search. Since dynamic programming involves stagewise decisions, it results in buildup-type procedures implemented in two different forms. The first procedure predicts a number of conformations by a completely discrete search and these are subsequently refined by local minimization. The second involves limited continuous local minimization within the combinatorial algorithm, generally restricted to two dihedral angles in a buildup step. Both procedures are tested on 17 short peptides previously studied by other global minimization methods but involving the same potential energy function. The discrete method is extremely fast, but proves to be successful only in 14 of the 17 test problems. The version with limited local minimization finds, however, conformations in all the 17 examples that are close to the ones previously presented in the literature or have lower energies. In addition, results are almost independent of the cutoff energy, the most important parameter governing the search. Although the limited local minimization increases the number of energy evaluations, the method still offers substantial advantages in speed. PMID- 2207286 TI - Structural effects of hydration: studies of lysozyme by 13C solids NMR. AB - 13C-nmr spectra of lysozyme obtained at 50.3 MHz using both static and magic angle-spinning-cross-polarization methods are reported at several water contents. The line widths and consequent resolution in the hydrated material is substantially improved over that in the lyophilized protein. The line narrowing is not commensurate with loss of a proton-carbon dipole-dipole coupling or dramatic changes in the relaxation parameters characterizing magnetization transfer from protons to carbon in the Hartmann-Hahn cross-polarization experiment. We interpret these data in terms of the water inducing a decrease in the distribution of local conformations sampled by the protein, although the magnitude of the conformational reorientations required to account for the data are not necessarily large nor do they imply a major unfolding of the protein on dehydration. PMID- 2207287 TI - Analysis of side-chain conformational distributions in neutrophil peptide-5 NMR structures. AB - The side-chain conformations have been analyzed in the antimicrobial peptide, Neutrophil Peptide-5 (NP-5), whose structure was independently generated from nmr derived distance constraints using a distance geometry algorithm. The side-chain and peptide dihedral angle distributions in the nmr structures were compared with those constructed from a data base of high-resolution protein crystal structures. The side-chain conformational preferences for NP-5 in solution are significantly different from those observed in the crystal structure data base. These results indicate that the side-chain conformations are quite disordered for many of the residues of NP-5. The absence of a correlation between the width of the conformational distribution and surface accessibility suggests that the disorder may be due to limitations in the structural information extracted from the nmr data rather than to molecular motion. However, it is also observed that the degree of conformational disorder is only weakly correlated with the number of nuclear Overhauser enhancements to a given side chain. Possible reasons for this are discussed. Molecular mechanics refinement of these structures did not significantly change the side-chain populations. Anomolously wide distributions are observed for rotations about the peptide bonds and the disulfide bonds in the NP-5 distance geometry structures, which are improved by the refinement. The very high degree of order observed for the central dihedral angle of the disulfide bond in the high-resolution crystal data base suggests that the rotation about this bond in proteins is determined by the local potential. PMID- 2207288 TI - Helix aggregation in peptide crystals: occurrence of either all parallel or antiparallel packing motifs for alpha-helices in polymorphs of Boc-Aib-Ala-Leu Ala-Leu-Aib-Leu-Ala-Leu-Aib-OMe. AB - Three crystalline polymorphs of the helical decapeptide, Boc-Aib-Ala-Leu-Ala-Leu Aib-Leu-Ala-Leu-Aib-OMe, have been obtained. Antiparallel helix aggregation is observed in crystals grown from methanol (A), while completely parallel packing is observed in crystals from isopropanol (B) or an ethylene glycol-ethanol mixture (C). Crystals B and C are very similar in molecular conformation and packing. The packing motifs in crystals A and B consist of rows of parallel molecules, with an almost identical arrangement in both crystals. In crystal A, adjacent rows assemble with the helix axes pointed in opposite directions, whereas in crystal B all rows assemble with helix axes pointed in the same direction. Electrostatic interactions between helix dipoles do not appear to be a major determinant of packing modes. The structures also do not provide a ready rationalization of packing preferences in terms of side-chain interactions or solvation. The alpha-helix of the peptide in crystal A has seven 5----1 hydrogen bonds; the helix in crystal B is a mixed 3(10)/alpha-helix. The crystal parameters are as follows. Crystal A: C51H92N10O13.CH3OH, space group P2(1) with a = 10.498 (1) A, b = 18.189 (3) A, c = 16.475 (3) A, beta = 99.28 (1) degree, Z = 2, R = 9.6% for 1860 data. Crystal B: C51H92N10O13.C3H7OH, space group P2(1) with a = 10.534 (1) A, b = 28.571 (4) A, c = 11.055 (2) A, beta = 95.74 (1) degree, Z = 2, R = 6.5% for 3251 data. Crystal C: C51H92N10O13.C2H5OH, space group P2(1), with a = 10.450 (1) A, b = 28.442 (5) A, c = 11.020 (2) A, beta = 95.44(1) degree, Z = 2, R = 14.8% (isotropic) for 1948 data. PMID- 2207290 TI - Gel electrophoresis of micron-sized particles: a problem and a solution. AB - The gel electrophoresis of spherical particles with a radius above 0.2 micron has not been reported yet. In the present study, video phase-contrast light microscopy is used to observe the motion of individual latex spheres, 0.52 micron in radius, during electrophoresis in 0.1% agarose gels. At 2 V/cm, the spheres initially migrate in the direction of the electrical field. However, each sphere eventually undergoes a cessation of all motion. Brownian motion is restored when the electrical potential gradient is reduced to zero. Arrest can be prevented by periodically inverting the direction of the electrical field. These observations are explained by electrical field-induced steric trapping of the spheres by gel fibers. Inversion of the electrical field should assist the application of agarose gel electrophoresis to micron-sized cellular organelles and cells. PMID- 2207289 TI - Conformational sampling using high-temperature molecular dynamics. AB - High-temperature molecular dynamics as a method for conformational search was explored on the antigen combining site of McPC 603, a phosphorylcholine binding immunoglobulin. Simulations at temperatures of 500, 800, and 1500 K were run for 111.5, 101.7, and 76.3 ps, respectively. The effectiveness of the search was assessed using a variety of methods. For the shorter hypervariable loops, molecular dynamics explored an appreciable fraction of the conformational space as evidenced by a comparison to a simple theoretical model of the size of the conformational space. However, for the longer loops and the antigen combining site as a whole, the simulation times were too short for a complete search. The simulations at 500 and 800 K both generated conformations that minimized to energies 200 kcal/mole lower than the crystal structure. However, the 1500 K simulation produced higher energy structures, even after minimization; in addition, this highest temperature run had many cis-trans peptide isomerizations. This suggests that 1500 K is too high a temperature for unconstrained conformational sampling. Comparison of the results of high temperature molecular dynamics with a direct conformational search method, [R. E. Bruccoleri & M. Karplus (1987) Biopolymers 26, 137-168]. showed that the two methods did not overlap much in conformational space. Simple geometric measures of the conformational space indicated that the direct method covered more space than molecular dynamics at the lower temperature, but not at 1500 K. The results suggest that high-temperature molecular dynamics can aid in conformational searches. PMID- 2207291 TI - Effects of cefotaxime on the serum protein binding of sulfisoxazole. AB - The possible acylating effects of cefotaxime on sulfisoxazole binding to serum proteins were evaluated in vitro in samples of human sera incubated with 50-1000 micrograms ml-1 cefotaxime at 37 degrees for 1 h and then dialyzed against saline. This incubation resulted in concentration-related increases in the free fraction of sulfisoxazole (+25 per cent, +30 per cent, and +45 per cent, with 250, 500, and 1000 micrograms ml-1 cefotaxime, respectively). Sulfisoxazole binding was also studied in samples of sera from patients given prophylactic cefotaxime (3 g d-1, IV) following elective surgery. Sulfisoxazole free fraction increased from 7.6 +/- 0.7 per cent in samples obtained before starting treatment to 9.2 +/- 0.8 per cent 24 h thereafter, and to 10.4 +/- 1.0 per cent after 5 days of treatment, but this difference was not statistically significant. A Scatchard plot of pooled samples showed a reduction in overall affinity (from 2.38 X 10(-4) M to 1.77 X 10(-4) M) without changes in the number of binding sites. The effects of cefotaxime on sulfisoxazole binding and kinetics were also studied experimentally in the rabbit. Treatment with 30 mg kg-1 cefotaxime t.i.d. for 2 days increased the unbound fraction of sulfisoxazole in vivo, from 17.2 +/- 2.9 per cent to 27.3 +/- 3.6 per cent (p less than 0.02). Treatment with high doses of cefotaxime, and perhaps other 3-acetoxymethylcephalosporins, may result in changes in the serum protein binding of some acidic drugs. PMID- 2207292 TI - Activation of beclomethasone dipropionate by hydrolysis to beclomethasone-17 monopropionate. AB - The relative affinity of beclomethasone (B), beclomethasone-17-monopropionate (17 BMP), beclomethasone-21-monopropionate (21-BMP), and beclomethasone dipropionate (BDP) has been determined. BDP binds to the glucocorticoid receptor with about half the affinity of the potent glucocorticoid dexamethasone (Dexa), B was found to be 0.75 times less active than Dexa. The 21-BMP has no binding affinity whereas the 17-BMP is about 13 times as potent as Dexa. The affinity data indicate that metabolism of BDP to 17-BMP is an important activation step. To evaluate the relationship between local and systemic activity incubation studies with BDP in human lung, simulated gastric and intestinal fluid and plasma were performed. In cytosol from human lung cells BDP is hydrolysed rapidly to the more stable 17-BMP. During gastric passage BDP is stable but is immediately hydrolysed to 17-BMP in intestinal fluid. In human plasma BDP is hydrolysed to 17-BMP and an interesterification of 17-BMP to the inactive 21-BMP was also found. PMID- 2207293 TI - Effects of inducers and inhibitors of mixed-function oxidases on the biliary excretion of pentacaine metabolites. AB - The biliary excretion of 3H-pentacaine and its metabolites was studied in rats pretreated with an inducer or inhibitor of mixed-function oxidases. Over one fourth (25.8 per cent) of a 2 mg kg-1 intraportal dose of 3H-pentacaine was excreted in bile in urethaneanaesthetized control rats within 3 h. The radioactivity appeared in the form of the parent drug, basic metabolites, and metabolite conjugates, 3.1, 86.5, and 10.4 per cent of the total radioactivity excreted, respectively. Pretreatment of rats with phenobarbital enhanced only slightly the biliary excretion of basic metabolites, and pretreatment with 3 methylcholanthrene had no effect. Phenobarbital also increased the initial rate of excretion of conjugates, but this effect was not sustained. 3 Methylcholanthrene had a tendency to impair excretion of conjugates by bile. Pretreatment of rats with SKF 525-A decreased the biliary excretion of both basic metabolites and conjugates while cimetidine did not alter significantly the biliary excretion of pentacaine metabolites. These results suggest that the canalicular transport of metabolites may be the most important factor in controlling pentacaine metabolite excretion in bile. PMID- 2207294 TI - Kinetics of biliary elimination of pentacaine in rats. AB - Pentacaine, a local anaesthetic of the carbanilate type, administered intravenously as 3H-pentacaine, 2 mg kg-1 to rats, was eliminated in the bile mainly in the form of metabolites (20.5 +/- 1.5 per cent of the dose) and as parent drug (0.1 per cent of the dose) within 3 days. In control rats 32.2 +/- 2.5 and 37.8 +/- 2.5 per cent of 3H-dose, representing pentacaine metabolites, were excreted in the urine and faeces, respectively. In bile-duct-cannulated rats 35.7 +/- 6.8, 11.2 +/- 3.4, and 20.5 +/- 1.5 per cent of 3H-dose were excreted in the urine, faeces, and bile, respectively. The high 3H recovered in faeces in animals with diverted bile flow indicated passage of pentacaine metabolites through the intestinal wall. The excretion of pentacaine and its metabolites in bile was an active process, since the ratio bile/plasma concentration rapidly attained values approaching 10. In rats with ligated ureters the biliary elimination of pentacaine and its metabolites was enhanced, compensating for impaired urinary excretion. This was accompanied by increased plasma and brain levels of 3H compared with untreated controls. PMID- 2207295 TI - Elevation of carbamazepine plasma levels by diltiazem in rabbits: a potentially important drug interaction. AB - The effect of diltiazem on the plasma level of carbamazepine (CBZ) was investigated in rabbits. The animals were given either CBZ alone or in combination with diltiazem and plasma samples were collected at different time intervals. The concentration of CBZ was detected using an HPLC method. Diltiazem significantly increased the area under the curve (AUC), the maximum plasma concentration (Cmax), and the elimination half-life (t1/2) of CBZ (p less than 0.05). These results suggest that a potentially harmful drug-drug interaction may occur if CBZ and diltiazem are administered concurrently. PMID- 2207297 TI - Species differences in the pharmacokinetics of recainam, a new anti-arrhythmic drug. AB - The pharmacokinetics of recainam, an anti-arrhythmic drug, were compared in mice, rats, rabbits, dogs, rhesus monkeys, and man. Bioavailability was virtually complete in monkeys and dogs, 67 per cent in man and 51 per cent in rats. Non linear kinetics between the oral and i.v. dose in rabbits precluded estimation of bioavailability. Linear plasma dose proportionality occurred in dogs between 6 and 60 mg kg-1 oral doses and rhesus monkeys between 1 and 15 mg kg-1 i.v. doses. A greater than proportional increase in the plasma AUC of recainam occurred between oral doses ranging from 54-208 mg kg-1 in mice, 25-110 mg kg-1 in rats, and 50-100 mg kg-1 in rabbits. In human subjects, the AUC/unit dose was linear between 400 and 800 mg. The terminal elimination t1/2 of recainam ranged from 1 5h in laboratory animals and man. The plasma Cmax and AUC of recainam were virtually identical after single or multiple (21 day) oral doses in dogs. After an i.v. dose, plasma clearance of recainam (l kg-1 .h) was 4.9-5.2 in rats and rabbits and 0.4-1.9 in dogs, rhesus monkeys, and man. The steady state volume of distribution was 2-5 times larger than the total body water of laboratory animals and man. Recainam was very poorly bound (10-45 per cent) to the serum proteins of rodents, rabbits, dogs, rhesus monkeys and man. In rhesus monkeys and man, recainam accounted for 10 per cent and 70 per cent, respectively, of the plasma radioactivity at 6 h post-dose. The pharmacokinetic profile of recainam in dogs most closely resembled that of man. PMID- 2207296 TI - Pharmacokinetics of morphine and its surrogates. XI: Effect of simultaneously administered naltrexone and morphine on the pharmacokinetics and pharmacodynamics of each in the dog. AB - There were no dramatic modifications of the pharmacokinetics in the dog of i.v. bolus doses of 0.5, 2.7 and 5 mg kg-1 morphine by coadministering i.v. 5 mg kg-1 naltrexone as bolus injections over 15-20s and 12.3 mg kg-1 by continuous infusion. Morphine's terminal half-life, clearances, apparent volumes of distribution (except for that of the central compartment), percentages of drug and conjugated metabolite excreted in urine and bile did not differ significantly by paired t-test (probability (p) greater than 0.05 for rejection of the null hypothesis of no difference) when naltrexone was coadministered. There were no statistically significant (by t-test) modifications of the plasma pharmacokinetics in the dog of i.v. bolus doses of 5 mg kg-1 naltrexone with and without morphine coadministration except for the coefficient of the second (or terminal) exponential of the sum that fitted the plasma concentration-time data of naltrexone. Although morphine coadministration did not significantly affect the terminal half-life of naltrexone, its clearances or apparent volumes of distribution by t-test of the differences between averages (with each dog equally weighted), drug coadministration did significantly (by t-test) affect the fraction of naltrexone dose secreted into bile as conjugate (fB), the fraction of the dose excreted as conjugate in urine, and the fraction excreted elsewhere (f'B). Although naltrexone reversed the central action of morphine in affecting monitored pupil diameters, it did not antagonize the peripheral effects of morphine in perturbing renal and biliary flow rates. This led to a larger fraction of the naltrexone dose being metabolized to conjugate on morphine coadministration. Since less naltrexone conjugate was renally and biliary excreted initially, due to morphine inhibition of the initial renal and biliary processes, naltrexone conjugate plasma concentrations were higher when morphine was coadministered. PMID- 2207298 TI - Microbially controlled drug delivery to the colon. AB - The human gastrointestinal tract consists of a highly complex ecosystem of aerobic and anaerobic microorganisms that plays a significant role in the metabolism of nutrients as well as drugs. In the colon, bacteria ferment various types of substrates that are not susceptible to digestion in the small intestine. This arouses interest in specific drugs, drug delivery systems, and prodrugs that escape small bowel digestion, arrive intact, and are absorbed or degraded in the large bowel. For the past forty years, experience has been gained with the azo prodrug of 5-amino salicylic acid, salazopyrine, which is cleaved by colonic bacteria to its parent drug. Some laxative drugs were also reported to degrade into active metabolites in the colon. Lately equally interesting and more sophisticated microbial controlled delivery systems, have been developed based on similar principles. PMID- 2207299 TI - MODFIT: a pharmacokinetics computer program. AB - This paper presents a computer program, MODFIT, written in FORTRAN, primarily for use on the Digital Equipment Company VAX series computers for the mathematical analysis of concentration-time data. Drug data generated from biological fluids and tissues may be fitted by a variety of different models. For many models, parameter starting estimates are program generated prior to automatic nonlinear regression analysis using a modified Davidon-Fletcher-Powell algorithm. The output of results is extensive and plotting facilities are available. Explicit and differential equation models may be fitted to single dose data and simulations using all models (single or repeat dose) may be employed to generate drug concentration-time data with plotting output. The package has been tested on numerous data with no problems regarding local function minima. Some comparisons with existing programs have been made and MODFIT compares well with respect to robustness, efficiency, and ease of use. PMID- 2207300 TI - Oxidative versus conjugative biotransformation of temazepam. AB - Twenty-four healthy volunteers, aged 21-59 years, received single 30 mg oral doses of the benzodiazepine hypnotic temazepam. Levels of intact temazepam were determined in multiple plasma samples drawn during 48 h after dosage. Intact temazepam, its direct glucuronide conjugate, and the conjugate of its demethylated (oxidized) metabolite oxazepam were measured in two consecutive 24-h urine collections. Mean kinetic variables for temazepam in plasma were: peak plasma level (Cmax), 873 ng ml-1; time of peak, 1.36 h after dosage; volume of distribution, 0.961 kg-1; elimination half-life 9.9 h; clearance, 1.16 ml min-1 kg-1. Volume of distribution increased significantly with body weight (r = 0.67, p less than 0.001), and Cmax decreased with weight (r = -0.58, p less than 0.01). Only 0.2 per cent of the dose was excreted as intact temazepam, and negligible amounts as intact oxazepam. However, 39 per cent of the dose was recovered as temazepam glucuronide, and oxazepam glucuronide accounted for another 4.7 per cent of the dose. The remainder was not accounted for. Thus, a significant fraction of temazepam clearance occurs by direct glucuronide conjugation, with the conjugate temazepam glucuronide excreted in urine. A much smaller fraction undergoes parallel oxidation to form oxazepam, which is subsequently conjugated to oxazepam glucuronide and excreted in urine. PMID- 2207301 TI - The relationship between the pharmacokinetics of ibuprofen enantiomers and the dose of racemic ibuprofen in humans. AB - Ibuprofen is a chiral drug which is used clinically as a racemate. The pharmacological properties of ibuprofen reside almost exclusively with the S(+) enantiomer. However, a portion of R(-)-ibuprofen is metabolically inverted to its pharmacologically active, mirror-image form. To investigate the influence of increasing dose of racemic ibuprofen on the pharmacokinetics of its individual enantiomers, four healthy male volunteers were given racemic ibuprofen (200, 400, 800, and 1200 mg), orally, on four occasions. The study was conducted using a balanced cross-over design. The extent of absorption of ibuprofen, as assessed by the total urinary recovery of ibuprofen and its metabolites, was extensive and independent of the administered dose. At all four doses, the area under the total and unbound plasma concentration-time curves (AUC and AUCu, respectively), and the unbound fraction in plasma, were significantly greater for the S(+) enantiomer. With increasing ibuprofen dose, there was a less than proportional increase in the AUC of each enantiomer, while the AUCu for both enantiomers increased in direct proportion to the administered dose. The time-averaged unbound fraction of each enantiomer increased significantly with increasing dose, which caused the non-linearity between AUC and dose. It was predicted that the metabolic intrinsic clearance of each enantiomer, and the fraction of R(-) ibuprofen which was metabolically inverted to S(+)-ibuprofen, was independent of the administered dose. PMID- 2207302 TI - Disposition of fluvastatin, an inhibitor of HMG-COA reductase, in mouse, rat, dog, and monkey. AB - The physiological disposition of fluvastatin, a potent inhibitor of hydroxymethylglutaryl-CoA reductase and thus cholesterol synthesis, has been studied in the mouse, rat, dog, and monkey using 14C- or 3H-labeled drug. Oral doses of fluvastatin were absorbed at a moderate to rapid rate. The extent of absorption was dose-independent and was essentially complete in all four species studied. However, the drug was subject to extensive presystemic hepatic extraction followed by direct excretion via the bile, thus minimizing the systemic burden and yielding high liver/peripheral tissue concentration gradients for fluvastatin and its metabolites. Only at high doses far exceeding the intended human daily dose of ca 0.6 mg kg-1 did fluvastatin bioavailability approach unity, apparently due to saturation of the first-pass effect. Dose normalized blood levels of fluvastatin and total radioactivity were higher in the dog than in the other species, suggesting a smaller distribution volume in the former. Fluvastatin was partially metabolized before excretion, the extent of metabolism being smallest in the dog and greatest in the mouse. The half-life of intact fluvastatin ranged from 1-2h in the monkey to 4-7h in the dog. Regardless of the dose or dose route, the administered radioactivity was recovered predominantly in feces, with the renal route accounting for less than 8 per cent of the dose. No tissue retention of radioactivity was observed, and material balance was essentially achieved within 96h after dosing. PMID- 2207303 TI - Pharmacokinetics of aditoprim in goats using a radioassay. AB - A simple, highly sensitive radioassay was developed for the activity of a newly discovered inhibitor of dihydrofolate reductase (DHFR), aditoprim. The procedure is based on the inhibition of binding of [3H]-methotrexate ([3H]MTX) with bacterial dihydrofolate reductase by the antifolate, aditoprim. The analytic sensitivity using this binding inhibition method was less than 5 ng in plasma. The procedure developed requires no extraction of the drug from the plasma. The variation of simultaneous duplicate determinations was 6.3 per cent, whereas the variability of plasma samples assayed on different days was less than 11 per cent. The assay developed was applied to study the pharmacokinetics of aditoprim in the goat. In comparison with trimethoprim (TMP), the new inhibitor of DHFR, aditoprim, had a longer half-life and a larger volume of distribution, suggesting enhanced and prolonged antibacterial activity of aditoprim over TMP. PMID- 2207304 TI - Pharmacokinetics and safety of single oral doses of lomefloxacin. AB - The pharmacokinetics of 100 mg, 200 mg, 400 mg, 600 mg, and 800 mg of lomefloxacin, a quinolone antimicrobial, were examined in a single sequential rising dose, placebo-controlled, crossover study. Each of 30 healthy male subjects (6 per group) received placebo and one dose of lomefloxacin, separated by 5 days. Test results (physical examinations, laboratory and hematology panels, vital signs, neurological and ophthalmological examinations, EEG or urinalysis) revealed no clinically significant differences compared to baseline. Mean Cmax values (0.92 micrograms ml-1 to 6.99 micrograms ml-1) increased linearly with dose. Mean tmax averaged 1.13 +/- 0.5 h and mean t1/2, 7.8 +/- 1.0 h over all doses. There was a small influence of dose on the AUC0-48. Mean urinary concentrations during the first 4 h postdosing ranged from 79 to 454 micrograms ml-1. Urine concentrations remained greater than or equal to 15 micrograms ml-1 over 24 h at the lowest dose. Maximum urinary excretion rate, Rmax, ranged from 5.84 mg h-1 to 34.90 mg h-1. Dose normalized Rmax and XU96 (per cent of dose) were unaffected by dose. Mean renal clearance decreased at higher doses. In conclusion, lomefloxacin was well tolerated in doses up to 800 mg. Lomefloxacin is rapidly absorbed with an elimination half-life of approximately 8 h. The data suggest that the drug can be effectively administered once daily. PMID- 2207305 TI - Minor histocompatibility antigens. PMID- 2207306 TI - Effects of recombinant human interleukin-3 in aplastic anemia. AB - In a phase I/II study, nine patients with aplastic anemia were treated with recombinant human interleukin-3 (rhIL-3) to assess the toxicity and biologic effects of this multipotential hematopoietic growth factor. Doses ranging from 250 micrograms/m2 to 500 micrograms/m2 were administered as subcutaneous bolus injections daily for 15 days. An increase in platelet counts from 1,000/microL to 31,000/microL was induced by rhIL-3 in one patient, and an increase in reticulocyte counts by more than 10,000/microL in four patients. The blood leukocyte counts temporarily increased in eight patients 1.5- to 3.3-fold (median, 1.8-fold), mainly due to an increase in the number of neutrophils, eosinophils, lymphocytes, and monocytes. In two patients, bone marrow cellularity increased from 7% to 33% and from 10% to 80%, respectively, but without resulting in a substantial improvement of peripheral blood counts. Mild side effects (headache and flushing) were observed in some patients, while low-grade fever occurred in all patients. Transient thrombocytopenia necessitating discontinuation of rhIL-3 treatment occurred in one patient. In conclusion, rhIL 3 can stimulate hematopoiesis in patients with aplastic anemia; however, no lasting effects were obtained. PMID- 2207307 TI - CEPP(B): an effective and well-tolerated regimen in poor-risk, aggressive non Hodgkin's lymphoma. AB - Eighty-three patients with intermediate- or high-grade non-Hodgkin's lymphoma were treated with CEPP(B) (cyclophosphamide, etoposide [VP-16], procarbazine, and prednisone with or without bleomycin) chemotherapy at Stanford University Medical Center (Stanford, CA) from January 1982 through June 1989. Sixty-nine received CEPP(B) as second-line or subsequent therapy after relapse from previous combination chemotherapy, and 14 patients received CEPP(B) as first-line therapy. Of 75 patients evaluable for response, 30 patients (40%) achieved a complete response (CR) and 24 patients (32%) achieved a partial response (PR), providing an overall response rate of 72%. Complete responses were recorded on 21 of 61 (34%) patients with recurrent disease and 9 of the 14 patients who received CEPP(B) as first line therapy (64%). Myelosuppression was the major side effect of treatment, resulting in eight neutropenic-febrile episodes from a total of 253 courses. A single fatal toxic event occurred on a patient who developed adult respiratory distress syndrome. Overall, CEPP(B) was well-tolerated and proved to be effective palliative therapy for patients with non-Hodgkin's lymphoma after relapse. As such, CEPP(B) may be considered for cytoreduction before ablative therapy and bone marrow transplantation. CEPP(B) may also be considered for initial therapy in selected patients who cannot tolerate doxorubicin-containing regimens. PMID- 2207308 TI - Selective regulation of the activity of different hematopoietic regulatory proteins by transforming growth factor beta 1 in normal and leukemic myeloid cells. AB - The viability of normal bone marrow myeloid precursor cells induced by interleukin-6 (IL-6) or IL-1 alpha and the ability of IL-6 and IL-1 alpha to induce the formation of colonies of granulocytes, macrophages, or megakaryocytes in densely seeded bone marrow cultures was suppressed by transforming growth factor-beta 1 (TGF-beta 1). Induction of normal bone marrow colony formation by IL-3 was much less sensitive to TGF-beta 1, and there was little or no effect of TGF-beta 1 on colony formation induced by macrophage colony-stimulating factor (M CSF) or granulocyte-macrophage CSF (GM-CSF). In different clones of myeloid leukemic cells, TGF-beta 1 suppressed differentiation induced with IL-6, IL-1 alpha, or lipopolysaccharide (LPS), but did not suppress differentiation induced with IL-3 or GM-CSF. The effect of TGF-beta 1 on differentiation of the leukemic cells can be dissociated from its effect on cell growth. TGF-beta 1 suppressed the production of IL-6 in normal bone marrow cells cultured with IL-1 alpha and the production of IL-6 and GM-CSF in leukemic cells cultured with IL-1 alpha or LPS. The suppression of IL-6 production can explain the suppression by TGF-beta 1 of the effects of IL-1 alpha and LPS that are mediated by IL-6. TGF-beta 1 also suppressed differentiation in clones of myeloid leukemic cells induced with differentiation factor/leukemia inhibitory factor and tumor necrosis factor. In different leukemic clones TGF-beta 1 suppressed or enhanced induction of differentiation with dexamethasone. The results show that TGF-beta 1 can selectively control the activity of different molecular regulators of normal and leukemic hematopoiesis. PMID- 2207309 TI - A specific in vitro bioassay for measuring erythropoietin levels in human serum and plasma. AB - The accurate measurement of biologically active erythropoietin (Ep) in human serum and plasma using present in vivo and in vitro bioassays is difficult because of the presence of both inhibitors and non-Ep stimulators of erythropoiesis. We have developed a simple procedure to quantitatively purify Ep from serum and plasma for subsequent testing in the phenylhydrazine-treated mouse spleen cell assay. The method involves absorption of Ep to an immobilized high affinity anti-Ep monoclonal antibody and acid elution of the antibody-bound material. After neutralization, the eluted EP is then tested directly in the in vitro bioassay without interference by other serum proteins. By using magnetic beads as a solid support for the antibody, washing and elution steps can be performed rapidly and efficiently. Recoveries of Ep after this procedure show very little sample-to-sample variation and are consistently between 45% and 55%, which is close to the maximum binding expected for the anti-Ep antibody. Coupled with the 7.4-fold concentration that this procedure affords, there is an overall increase in sensitivity of three- to fourfold, which makes this assay suitable for accurately measuring Ep levels in patients with below-average titers. Results with this magnetic bead assay indicate that accurate and reproducible estimates for Ep levels in the serum and plasma from healthy donors as well as from patients with hematologic disorders can be obtained. Titers of biologically active Ep in the sera from a group of patients with either leukemia or lymphoma were found to be elevated, and the values correlated well with titers of immunoreactive Ep measured in the Ep radioimmunoassay. Because of its specificity and high sensitivity, the magnetic bead assay is a valuable alternative to immunoassays for the measurement of elevated, normal, and even subnormal Ep levels in human serum and plasma. PMID- 2207310 TI - Induction of mixed erythroid-megakaryocyte colonies and bipotential blast cell colonies by recombinant human erythropoietin in serum-free culture. AB - The effects of recombinant human erythropoietin (rEp) on murine hematopoietic progenitors were studied using a serum-free culture. A high concentration of rEp stimulated the formation of mixed erythroid-megakaryocyte colonies (EM colonies) and blast cell colonies, as well as erythroid colonies, erythroid bursts, and megakaryocyte colonies from normal mouse bone marrow cells. Direct effects of rEp on EM colony, megakaryocyte colony, and erythroid burst formation were confirmed by depletion of accessory cells such as T cells, B cells, and macrophages from crude bone marrow cells, and inhibition of the colonies by the addition of rabbit anti-rEp antibody to the culture in a dose-dependent fashion. Replating experiments were performed to confirm the differentiating ability of blast cell colonies grown in the presence of rEp. Most of the blast cell colonies yielded not only secondary erythroid colonies but also megakaryocyte colonies in the presence of 2 IU/mL rEp. Some of the blast cell colonies produced secondary EM colonies in the presence of 16 IU/ml rEp of 2 IU/mL rEp plus interleukin-3, although no granulocyte-macrophage colonies were found in the secondary culture. These results suggest that Ep acts not only as a late-acting factor that is specific for erythroid progenitors, but also as a bipotential EM-stimulating factor for murine hematopoietic cells. PMID- 2207311 TI - Uremic platelets have a functional defect affecting the interaction of von Willebrand factor with glycoprotein IIb-IIIa. AB - Uremic patients have an impaired platelet function that has been related to membrane glycoprotein (GP) abnormalities. Using a perfusion system, we have studied the interaction of normal and uremic platelets with vessel subendothelium (SE) under flow conditions. Reconstituted blood containing washed platelets, purified von Willebrand factor (vWF) (1 U/mL), and normal washed red blood cells was exposed to de-endothelialized rabbit segments for 10 minutes at two different shear rates (800 and 1,600 seconds-1). In some experiments a monoclonal antibody to the GPIIb-IIIa complex (EDU3) was added to the perfusates. With normal platelets, the percentage of the vessel covered by platelets (%CS) was 23.1% +/- 3.7% at 800 seconds-1 and 30% +/- 4.3% at 1,600 seconds-1. Platelets were observed in contact or forming monolayers on vessel SE. EDU3 inhibited the spreading of normal platelets. The %CS (11.1% +/- 3.3%) was statistically decreased (P less than .01) and most of the platelets were observed in contact with the vessel surface. These data indicate that, under flow conditions, the interaction of vWF with GPIIb-IIIa can support the spreading of normal platelets in the absence of exogenous fibrinogen. Under the same experimental conditions, the interaction of uremic platelets with SE was markedly impaired at both shear rates studied (P less than .01 v normal platelets). The presence of EDU3 did not modify the interaction of uremic platelets. These results confirm the impairment of the platelet adhesion observed in uremic patients. Furthermore, they indicate the presence of a functional defect in the interaction of vWF with GPIIb-IIIa. The fact that perfusions with normal and uremic platelets in the presence of an antibody to the GPIIb-IIIa complex did not show any differences gives indirect evidence on a functionally normal interaction vWF/GPIb in uremic patients. PMID- 2207312 TI - Lymphokine-activated killer (LAK) cell activity in B and T chronic lymphoid leukemia: defective LAK generation and reduced susceptibility of the leukemic cells to allogeneic and autologous LAK effectors. AB - The capacity to generate lymphokine-activated killer (LAK) cells and the susceptibility of the neoplastic cells to both allogeneic and autologous LAK effectors were studied in B and T chronic lymphoproliferative disorders. While in B-cell chronic lymphocytic leukemia (B-CLL) the depressed natural killer function could be restored after a 7-day incubation with recombinant interleukin (IL-2), B CLL mononuclear cells showed a reduced LAK activity compared with normal LAK cells. Furthermore, in all but 1 of the 20 B-CLL samples tested the leukemic cells were totally resistant to autologous LAK effectors. In most cases the leukemic cells were also resistant to normal allogeneic LAK cells. Competition experiments demonstrated that the patients' LAK cells, as well as normal LAK effectors, were capable of recognizing B-CLL cells, pointing, therefore, to a postbinding cytolytic defect. In hairy cell leukemia (HCL) an overall reduced LAK activity against allogeneic targets was documented, but, at variance from B-CLL, hairy cells were often susceptible to the lytic effect of normal LAK cells, and in half of the cases tested the neoplastic population was also sensitive in an autologous system. Similarly to B-CLL, in the great majority of T chronic lymphoproliferative disorders studied, the pathologic cells were resistant to normal and autologous LAK effectors and a defective LAK generation was found. These results demonstrate that in most B and T chronic leukemias the LAK function is defective and, when inducible, does not appear directed against the leukemic population. The possibility of exploiting an immunotherapeutic approach with IL 2/LAK cells in the management of chronic lymphoproliferative disorders does not gain support by these findings. PMID- 2207313 TI - Distinct characteristics of lymphokine-activated killer (LAK) cells derived from patients with B-cell chronic lymphocytic leukemia (B-CLL). A factor in B-CLL serum promotes natural killer cell-like LAK cell growth. AB - We show that lymphokine-activated killer (LAK) cell precursors derived from patients with B-cell chronic lymphocytic leukemia (B-CLL) and cultured in the presence of recombinant interleukin-2 and normal human serum (NHS), develop into primarily NK cell-like (CD 57+) LAK cells, whereas identically prepared LAK cell precursors from normal subjects develop into mainly T cell-like (CD 3+, CD 8+) LAK cells. B-CLL LAK cells exhibited greater proliferative capacity than did normal LAK cells. When normal LAK cells were grown in B-CLL serum instead of NHS, their proliferation increased; NK cell levels also increased to those found in B CLL LAK cells, suggesting that B-CLL serum contains a factor that promotes NK cell-like growth, LAK cells derived from normal or B-CLL patients demonstrated similar lytic activity toward K562 and Raji cells. Growth in B-CLL serum did not reduce their lytic potential. Thus, the altered phenotype and growth exhibited by B-CLL LAK cells and normal LAK cells grown in B-CLL serum does not lead to abnormalities in their cytolytic functions. We propose instead that the predominance of NK-like cells in B-CLL LAK cell populations and the presence of an NK cell-like growth factor in B-CLL serum reflect abnormalities related to NK cell-mediated B-cell regulation; ie, either inhibition of normal B-cell growth and/or growth stimulation of the leukemic clone in B-CLL. PMID- 2207314 TI - Genotypic characterization of centrocytic lymphoma: frequent rearrangement of the chromosome 11 bcl-1 locus. AB - Centrocytic lymphomas are defined in the Kiel classification as B-cell lymphomas composed exclusively of cells resembling cleaved follicular center cells (FCC). These lymphomas have been shown to be histologically, immunophenotypically, and clinically distinct from other cleaved FCC lymphomas. DNA from 18 centrocytic lymphomas (14 patients) was analyzed using Southern blotting and probes for immunoglobulin heavy (JH) and kappa light chain (JK) joining gene, T-cell receptor beta chain constant gene (CB), bcl-1, bcl-2, and c-myc gene rearrangements. All of the lymphomas had JH and JK rearrangements, confirming their B-cell origin. None of the specimens had detectable CB, bcl-2, or c-myc rearrangements. However, 4 of 14 patients (28.6%) had rearrangement of the chromosome 11 bcl-1 locus. Therefore, centrocytic lymphomas are genotypically distinguishable from the majority of other small cleaved FCC lymphomas by their lack of demonstrable bcl-2 rearrangements. This supports the distinct nature of centrocytic lymphomas and suggests the lack of importance for the putative oncogene bcl-2 in these cases. Furthermore, the frequent rearrangement of bcl-1 suggests a possible role for this locus in the pathogenesis of at least some centrocytic lymphomas. PMID- 2207315 TI - Release of tumor necrosis factor by human polymorphonuclear leukocytes. AB - Evidence is presented that human polymorphonuclear neutrophils (PMN) can be induced to produce tumor necrosis factor (TNF). Other investigators have previously reported that TNF has been induced from macrophages by bacteria and, more recently, from natural killer cells by certain tumor cells. Our laboratory has reported that the opportunistic fungi, Candida albicans, can induce TNF, not only from human monocytes, but also from Percoll-fractionated large granular lymphocytes. We now report that incubation of PMN with C albicans for 3 hours was sufficient for detection of TNF release, and peak induction was observed at 8 to 18 hours. This release was inhibitable by actinomycin D, an inhibitor of RNA synthesis, as well as by emetine and cycloheximide, which block protein synthesis. The TNF produced by PMN was neutralized by specific monoclonal antibodies against human TNF. These results represent an important finding that TNF production is a normal response of PMN to stimulation by fungi such as C albicans and suggest that the release of TNF may be related to autocrine activation of PMN effector function to control Candida growth. PMID- 2207316 TI - Reconstitution of antibody response after allogeneic bone marrow transplantation: effect of lymphocyte depletion by counterflow centrifugal elutriation on the expression of hemagglutinins. AB - The generation of ABO hemagglutinins was used as a model to assess the tempo of reconstitution of antibody responses in recipients of elutriated (CCE) and nonelutriated (nonCCE) HLA matched bone marrow allografts. The study included 29 CCE recipients (10 major, 6 minor, and 1 major/minor ABO-mismatched, and 12 ABO matched) and 40 nonCCE recipients (14 major, 12 minor, 2 major/minor, and 12 matched). Plasma volume in the graft and in blood product transfusions was uncorrelated with changes in hemagglutinin titers and therefore was excluded as a significant source of antibody. Removal of graft lymphocytes by CCE did not result in prolongation of host-derived hemagglutinins in recipients of major ABO mismatched grafts. However, CCE resulted in a complete abrogation of the adoptive transfer of donor-derived antibody as detected in recipients of minor ABO mismatched grafts. Despite the absence of adoptively transferred donor immunity in recipients of CCE grafts, they had hemagglutinin levels comparable with those of recipients of nonCCE grafts by 6 months after transplantation. This demonstrates that recipients of elutriated marrow were competent to mount de novo responses at that time. The strong correlation between donor pretransplant hemagglutinin titer and recipient titer 1 year after bone marrow transplantation in recipients of nonCCE grafts suggests that even late after transplant, antibody remains the product of adoptively transferred memory cells in recipients of grafts containing large numbers of mature lymphocytes. PMID- 2207317 TI - Anti-asialo GM1 antiserum treatment of lethally irradiated recipients before bone marrow transplantation: evidence that recipient natural killer depletion enhances survival, engraftment, and hematopoietic recovery. AB - Natural killer (NK) cells are reported to have an important role in the resistance of lethally irradiated recipients to bone marrow transplantation (BMT). Therefore, we investigated the effects of recipient NK depletion on survival, chimerism, and hematopoietic reconstitution after lethal irradiation and the transplantation of limiting amounts of T-cell-deficient bone marrow (BM). When administered before BMT, anti-asialo GM1 (ASGM1) antiserum treatment, effective in depleting in vivo NK activity, was associated with a marked increase in survival in 3 of 3 allogeneic combinations (BALB/c into C3H/HeN, C57B1/6, or C3B6F1). This enhanced survival was independent of the susceptibility of each recipient strain to accept BALB/c BM. Moreover, recipient anti-ASGM1 treatment was also effective in increasing survival in recipients of syngeneic BM, suggesting that NK cells can adversely affect engraftment independent of genetically controlled polymorphic cell surface determinants. Analysis of chimerism in surviving animals 2 months post-BMT showed that recipient NK depletion significantly increased the level of donor engraftment when high doses of BM were transplanted. These studies also demonstrated that anti-ASGM1 pretreatment mainly resulted in an increase in extramedullary hematopoiesis in the second and third week after irradiation. Anti-ASGM1 treatment also dramatically accelerated the rate of appearance of donor-derived cells with a higher level of donor-cell engraftment apparent at a time when the differences in survival between NK-depleted and control BMT recipients became significant. Peripheral cell counts were also affected by NK depletion, with significantly enhanced platelet and red blood cell recovery and a moderate increase in granulocyte recovery. The overall favorable influence of anti-ASGM1 recipient treatment on hematopoietic events post-BMT suggests that, in humans, pretransplant regimens aimed toward NK depletion should be evaluated. PMID- 2207318 TI - Transfusion and alloimmunization in sickle cell disease. The Cooperative Study of Sickle Cell Disease. AB - In 1,814 patients with sickle cell disease who had been transfused, the overall rate of alloimmunization to erythrocyte antigens was 18.6%. The rate of alloimmunization in this group appears to be an explicit function of the number of transfusions received because it increases exponentially with increasing numbers of transfusions. Alloimmunization usually occurred with less than 15 transfusions, although the rate of alloimmunization continued to increase when more transfusions were given. The rate of alloimmunization was less in patients with hemoglobin SC disease and sickle-beta+ thalassemia because these patients had received fewer transfusions. Children less than 10 years old had a slightly lower rate of alloimmunization than patients in other age groups even after correction for the number of transfusions given. Women were more frequently alloimmunized than men; this was largely due to the fact that women received more transfusions than men, but in the age group 16 to 20 years the increase may have been due in part to alloimmunization owing to pregnancy. Forty-five percent of those alloimmunized made antibodies of only one specificity; 17% made four or more antibodies reacting with different antigens. Antibodies to the C and E antigens of the Rh group, the Kell antigen, and the Lewis antigens were most commonly made. These findings may be important in formulating a rational transfusion policy in sickle cell disease. PMID- 2207319 TI - Reproduction of transfusion-related acute lung injury in an ex vivo lung model. AB - Leukoagglutinins are implicated in transfusion-related acute lung injury (TRALI). In the present study, severe lung vascular leakage was reproduced by application of a leukoagglutinating antibody of anti-5b specificity in an ex vivo lung model. The antibody originated from a multiparous donor-plasma, observed to cause noncardiogenic edema during transfusion therapy. Heated full plasma (anti-5b titer 1/128) or purified immunoglobulin G fraction was used for the studies. Ex vivo isolated rabbit lungs were perfused with albumin buffer, and human granulocytes (PMN) were admixed to the recirculating perfusate. In presence of anti-5b antibody plus 5b-positive PMN plus rabbit plasma as complement-source, severe lung edema occurred after a latent period of 3 to 6 hours. Pulmonary artery pressure was only transiently and moderately increased, and the leakage reaction could be traced back to a several-fold increase in lung vascular permeability. In contrast, no vascular leakage was noted in lungs perfused in the absence of anti-5b antibody, PMN, or rabbit plasma. Moreover, no permeability increase occurred on use of 5b-negative PMN. This reproduction of TRALI in an ex vivo lung model corroborates the role of leukoagglutinating antibodies in initiating PMN-dependent respiratory distress and suggests a contribution of concomitant complement activation. PMID- 2207320 TI - Biology and clinical significance of cytogenetic abnormalities in childhood acute lymphoblastic leukemia. AB - Virtually all cases of childhood ALL have chromosomal abnormalities and half contain translocations, which are nearly equally divided between random and nonrandom rearrangements. Nonrandom chromosomal abnormalities have been correlated with leukemic cell lineage, the degree of cell differentiation, and the specific gene involved at the molecular level. Many cytogenetic findings have prognostic significance; however, the adverse influence of certain changes, including most chromosomal translocations, may in fact be offset by the greater cytoreductive effects of intensified therapy. Table 4 summarizes the relation of selected karyotypic findings to treatment outcome in patients treated on contemporary protocols. Among all of the chromosomal abnormalities identified in childhood ALL, hyperdiploidy greater than 50 has been associated with the most favorable prognosis. At the opposite end of the spectrum, the treatment outcome for patients with classical Ph+ or hypodiploid ALL is very poor even in programs of intensive chemotherapy; alternative treatment such as bone marrow transplantation should be considered for such patients. Cases with the t(4;11)(q21;q23) also have a very poor clinical outcome, but the adverse prognosis may be limited to the infant or adolescent age groups. The prognostic significance of other nonrandom translocations, such as t(1;19)(q23;p13) and several other abnormalities, needs to be further assessed in larger numbers of patients. Finally, as more is learned about the molecular pathology underlying these rearrangements, it may be possible to develop new therapeutic agents that are specifically targeted to interfere with the aberrant gene products expressed by human leukemic cells. PMID- 2207322 TI - In vivo stimulation of megakaryocytopoiesis by recombinant murine granulocyte macrophage colony-stimulating factor. AB - Murine recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) was injected in mice, and the effects on bone marrow, splenic megakaryocytes, megakaryocyte precursors (megakaryocyte colony-forming units [CFU-Meg]) were evaluated. In mice injected three times a day for 6 days with 12,000 to 120,000 U rGM-CSF, no significant modification of both platelet levels and mean platelet volume was observed, while there was a twofold increase in blood neutrophils. However, the rate of platelet production, as assessed by the measurement of 75selenomethionine incorporation into blood platelets, was On the contrary, administration of up to 384,000 U rGM-CSF two times a day for 2 days, as for a typical "thrombopoietin assay," failed to modify platelet production. A significant dose-related increase in the number of splenic megakaryocytes occurred in mice receiving 60,000 to 120,000 U rGM-CSF, while a slight increase in the number of bone marrow megakaryocytes was observed in mice injected with 120,000 U rGM-CSF. The proportion of bone marrow megakaryocytes with a size less than 18 microns and greater than 35 microns resulted significantly higher in mice receiving rGM-CSF in comparison with controls; an increase in the percentage of splenic megakaryocytes greater than 35 microns was also observed. A statistically significant increase in the total spleen content of CFU-Meg was observed after administration of 90,000 and 120,000 U rGM-CSF three times a day for 6 days, while no effect on bone marrow CFU-Meg was recorded, irrespective of the dose delivered. Finally, 24 hours after a single intravenous injection of rGM-CSF, there was a significant increase in the proportion of CFU-Meg in S-phase, with the splenic progenitors being more sensitive than bone marrow-derived CFU-Meg. These data indicate that rGM-CSF has in vivo megakaryocyte stimulatory activity, and are consistent with previous in vitro observations. However, an effective stimulation of megakaryocytopoiesis in vivo, bringing about an increase in the levels of blood platelets, may require interaction of rGM-CSF with other cytokines. PMID- 2207321 TI - A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment. AB - We have reviewed results of therapy in 740 patients with grades II-IV acute graft versus-host disease (GVHD) after allogeneic marrow transplantation. At the beginning of therapy, 597 patients (81%) had rash, 369 (50%) had liver dysfunction and 396 (54%) had gut dysfunction. Initial treatment was with glucocorticoids (n = 531), cyclosporine (n = 170), antithymocyte globulin (ATG) (n = 156) or monoclonal antibody (n = 3) either singly (n = 633) or in combination (n = 107). Parameters of GVHD severity in each organ were recorded weekly, and evaluation of response was made using values at the initiation of secondary treatment or, for patients without such treatment, using values on day 29 of primary treatment or the last recorded value before death, whichever occurred first. Minimal criteria for improvement or progression were defined for each organ, but no attempt was made to define liver or gut outcome if another complication such as venocclusive disease or infectious enteritis was present. Improvement rates were 43% for skin disease, 35% for evaluable liver disease and 50% for evaluable gut disease. Overall complete or partial responses were seen in 44% of patients. Multivariate analyses were carried out to identify patient, disease or treatment factors associated with likelihood of overall improvement and likelihood of response in at least one organ. A similar analysis was also carried out to identify covariates associated with time to treatment failure (defined as initiation of secondary therapy or death not due to relapse of malignancy). In all three models, GVHD prophylaxis using cyclosporine combined with methotrexate was associated with favorable GVHD treatment outcome compared to prophylaxis with either agent alone, and treatment with glucocorticoids or cyclosporine was more successful than treatment with ATG. Other factors associated with unfavorable outcome in the model of time to treatment failure and also entered in one of the response models were recipient HLA disparity with the donor, presence of a liver complication other than GVHD, and early onset of GVHD. Results of this analysis indicate that glucocorticoids represent the best initial therapy available for treatment of acute GVHD, although much room for improvement remains. PMID- 2207323 TI - Coordinate secretion of interleukin-1 beta and granulocyte-macrophage colony stimulating factor by the blast cells of acute myeloblastic leukemia: role of interleukin-1 as an endogenous inducer. AB - Acute myeloblastic leukemia (AML) blasts have been shown to produce a variety of cytokines in culture such as interleukin-1 (IL-1), IL-6, granulocyte-, macrophage , and granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF alpha). Using two sensitive and specific enzyme-linked immunosorbent assays for IL-1 beta and GM-CSF, we document in the present study that the production of the two cytokines by AML blasts in culture is coordinated. First, we observe a striking correlation between the levels of GM-CSF and IL-1 beta released by the cells. Thus, a high production of IL-1 beta is always concordant with a high production of GM-CSF and, conversely, low production of IL 1 beta is concordant with low levels of GM-CSF. Second, neutralization of intrinsic IL-1 using antibodies that are specific for IL-1 alpha and -1 beta suppresses the release of GM-CSF by the cells. Third, neutralization of the endogenous source of IL-1 also results in an abrogation of GM-CSF mRNA. Fourth, the production of both IL-1 beta and GM-CSF is up-regulated by exposing AML blasts to an exogenous source of IL-1, suggesting a positive regulation of autocrine growth factor production. Taken together, our results indicate that GM CSF production by AML blasts is mediated by endogenously produced IL-1. Both IL-1 beta and -1 alpha are produced by AML blasts, although IL-1 beta appears to be more abundant. Spontaneous colony formation by AML blasts is abrogated by the addition of neutralizing antibodies against IL-1 beta and GM-CSF, whereas each antibody alone has little effect on blast proliferation. Taken together, our results are consistent with the view that the production of IL-1 beta by AML blasts supports autocrine growth in culture, through induction of CSFs or other cytokines that stimulate blast proliferation. PMID- 2207324 TI - Induction of monocyte proliferation and HIV expression by IL-3 does not interfere with anti-viral activity of zidovudine. AB - Myelosuppression is a major symptom in the acquired immunodeficiency syndrome (AIDS). Moreover zidovudine, an anti-retroviral drug used to treat AIDS patients has myelosuppressive side effects. Therefore treatment with IL-3, a multi-lineage hemopoietic growth factor may be beneficial for zidovudine-treated individuals. In this study we examined the effect of IL-3 on human immunodeficiency virus (HIV) expression. The proliferative response to rIL-3 and the effects on the replication of the monocytotropic HIV variant, HTLV-III Ba-L, in the absence or presence of the anti-retroviral drug zidovudine was studied in purified human peripheral blood monocytes. Zidovudine concentrations sufficient for complete inhibition of HIV replication did not affect rIL-3 induced monocyte proliferation. Although rIL-3, like rGM-CSF, was able to augment HIV expression in monocytes, it did not interfere with the anti-retroviral activity of zidovudine. These data indicate that rIL-3 is a potential candidate for use in myelosupportive therapy in AIDS patients treated with anti-retroviral drugs. PMID- 2207325 TI - Effects of recombinant human interleukin-3 on human hematopoietic progenitor and precursor cells in vivo. AB - DNA-synthesis rates and concentrations of bone marrow (BM) and peripheral blood (PB) progenitor cells were studied in 22 patients treated with recombinant human interleukin-3 (rhIL3) as part of a clinical phase I/II study. Recombinant hIL3 at doses of 60 to 500 micrograms/m2 was administered by subcutaneous bolus injection for 15 days to 13 patients with solid tumors and preserved hematopoietic function and to nine patients with bone marrow failure, including five with myelodysplastic syndromes. Following treatment with rhIL3, the percentage of actively cycling BM erythroid (BFU-E) and multilineage (CFU-GEMM) progenitors in patients with preserved hematopoietic function increased from 16% to 36% (P less than .05) and from 10% to 40% (P less than .01), respectively. The DNA-synthesis rates of early and late granulocyte macrophage progenitor cells increased from 11% to 26% (CFU-GM day 14; P less than .02) and from 13% to 30% (CFU-GM day 7; P less than .05). There was an increase in BM cellularity from 37% to 58%, and of the myeloid to erythroid ratio from 1.4 to 3.2, while the concentration of marrow progenitors on a per cell basis was unchanged or slightly decreased. The frequencies of blast cells in the BM were unchanged. Mean levels of PB CFU-GM day 14 and CFU-GEMM were 100% and 72% above baseline values after 7 days of rhIL3 but only 25% and 28% above initial levels at the end of treatment. Peripheral blood BFU-E were reduced in the majority of patients with normal marrow after both 7 and 15 days of rhIL3. No augmentation of circulating BFU-E and CFU-GEMM was seen in 5 patients with MDS who had few or no PB BFU-E or CFU-GEMM initially. Total leukocyte, neutrophil, and eosinophil counts increased significantly (P less than .01) in 21 of 22 patients with a peak response after a median of 13 days of rhIL3. While a small increase in reticulocytes was not accompanied by an elevation of the hemoglobin or hematocrit, platelet counts increased by 50% in patients with preserved marrow function. Thus, rhIL3 induces a multilineage response in vivo, apparently by stimulating proliferation of multipotential and lineage-restricted progenitors. It remains to be determined whether this is due to direct or indirect effects on the progenitor cells. PMID- 2207327 TI - The pharmacokinetics of plasminogen activator inhibitor-1 in the rabbit. AB - The pharmacokinetics of the activated and latent forms of plasminogen activator inhibitor-1 (PAI-1) isolated from HT1080 fibrosarcoma cells (HT1080 PAI-1) and a nonglycosylated form of human PAI-1 isolated from a yeast expression system (rPAI 1) were followed in the rabbit. As assessed by an immunologic assay specific for human PAI-1, guanidine HCI activated HT1080 PAI-1 and rPAI-1 entered the total plasma volume following intravenous bolus administration and exhibited a biphasic clearance pattern. The t1/2s of HT1080 PAI-1 for the initial and beta phases equalled 6.0 and 24.8 minutes, respectively. The t1/2s of rPAI-1 for the initial and beta phases equalled 8.8 and 34.0 minutes, respectively. Similar results were obtained by measuring PAI-1 activity in plasma and with trace amounts of 125I rPAI-1, suggesting that the above pharmacokinetic behavior could also apply to endogenous PAI-1. The liver was the main site of rPAI-1 clearance. Unactivated, latent PAI-1 exhibited a very different pharmacokinetic profile. Over 80% of latent rPAI-1 cleared from the circulation within 10 minutes (t1/2 = 1.7 minutes). The difference in clearance behavior between activated and latent PAI-1 may be related to the ability of activated PAI-1, but not latent PAI-1, to rapidly form high-molecular-weight complexes with plasma binding factors which were observed in vitro and in vivo. Because PAI-1 could potentially tilt the fibrinolytic balance toward a prothrombotic state, its rapid clearance may represent an important control mechanism governing the circulating levels of this key component of the fibrinolytic pathway. PMID- 2207326 TI - Thrombin induces a rapid redistribution of glycoprotein Ib-IX complexes within the membrane systems of activated human platelets. AB - Previous studies have shown a decreased binding of monoclonal antibodies (MoAbs) to glycoprotein (GP) Ib-IX complexes on thrombin-stimulated platelets, but the reason for this is poorly understood. We have used (1) immunofluorescence procedures and flow cytometry, and (2) immunogold staining and electron microscopy to investigate this phenomenon. Washed platelets were incubated with alpha-thrombin, adenosine diphosphate, or ionophore A23187 for increasing lengths of time. For alpha-thrombin, but not the other agonists, flow cytometry confirmed a dose- and time-dependent decrease in the binding of MoAbs specific for GP Ib alpha (AP-1, Bx-1), GP IX (FMC 25), or to the complex itself (SZ 1). Immunoglold staining performed using standard transmission or scanning electron microscopy high-lighted surface areas devoid of bound antibody. However, a quantitatively normal immunofluorescence was restored if paraformaldehyde-fixed, thrombin stimulated platelets were permeabilized with Triton X-100 (Sigma Chemical Co, St Louis, MO) before MoAb addition, while immunogold staining was now seen to be concentrated within the interior of the platelet. Glutaraldehyde-fixed samples were then embedded in the resin Lowicryl K4M (Taab Laboratories Equipment Ltd, Aldermaston, England) and immunogold staining performed on thin sections using a polyclonal antibody to glycocalicin. An increased presence of GP Ib-IX complexes within surface-connected membrane systems of the thrombin-stimulated platelets was confirmed. Interestingly, GP Ib-IX movement was opposite to the thrombin induced externalization of internal pools of GP IIb-IIIa complexes and of the alpha-granule membrane GP, GMP-140. PMID- 2207328 TI - Expression in a cell-free system of normal and variant forms of human antithrombin III. Ability to bind heparin and react with alpha-thrombin. AB - Human antithrombin III (AT-III) cDNA was cloned into the cell-free expression phagemid vector pGEM-3Zf(+) and site-directed mutagenesis was used to remove nucleotides encoding the signal peptide. AT-III messenger RNA (mRNA) transcripts derived from this construct were translated in an mRNA-dependent rabbit reticulocyte lysate (RRL) system containing (35S)methionine. Immunoprecipitation of the cell-free translation mixture with rabbit polyclonal antibodies to AT-III showed, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), a 47-Kd polypeptide which is the non-glycosylated mature form of plasma AT-III. Densitometric scanning showed that this polypeptide constitutes greater than 90% of the radiolabeled polypeptides produced in this system. Heparin-Sepharose chromatography resulted in the elution of cell-free derived AT-III as a broad peak between 0.2 and 0.7 mol/L NaCl. The cell-free derived AT-III also reacted with human alpha-thrombin. In 2 minutes approximately 20% of the AT-III was found associated with a higher molecular weight species, consistent with the formation of a 1:1 stoichiometric covalent complex between alpha-thrombin and AT-III. Unfractionated heparin accelerated the rate of formation of such complexes. When Ser394 was mutated to Leu to form the AT-III Denver mutant, the cell-free translation product of this mutation did not show any significant complex formation when reacted with alpha-thrombin. A truncated form of AT-III (Met251 Lys432), containing only the putative thrombin-binding domain, was synthesized independently. This 21-Kd polypeptide did not bind heparin; however, it was cleaved by alpha-thrombin presumably at the reactive center Arg393-Ser394. When Ser394 was mutated to Leu the cell-free translation product of this truncated AT III mutation did not react with alpha-thrombin at the reactive center. This simple cell-free approach, along with site-directed mutagenesis, should allow for the rapid and accurate mapping of the functional domains of human AT-III. PMID- 2207330 TI - Monoclonal antibodies bound to subunits of the integrin GPIIb-IIIa are internalized and interfere with filopodia formation and platelet aggregation. AB - The monoclonal antibodies Tab and AP3 are directed, respectively, against GPIIb and GPIIIa, the subunits of the platelet fibrinogen receptor. When added together to platelets, these antibodies prevent adenosine diphosphate (ADP)-induced platelet aggregation, despite normal fibrinogen binding (Newman et al, Blood 69:668, 1987). To explore the cellular requirements of aggregation after fibrinogen binding, we used several techniques to study platelets treated with Tab and AP3, then stimulated with ADP. We used scanning and transmission electron microscopy to evaluate platelet morphology, immunolabel-surface replication to determine whether individual GPIIb-IIIa complexes clustered, immunocytochemistry on frozen thin sections to study the subcellular distribution of the integrin GPIIb-IIIa and fibrinogen, and biochemical methods to assess the activation of the platelet cytoskeleton. We found that the treated cells had short, blunted projections instead of normal filopodia. Other morphologic abnormalities, apparent in thin section, were aberrantly placed alpha-granules and microtubules, and a prominent, worm-like, fibrinogen-filled surface-connected canalicular system. Biochemical analysis suggested that such platelets undergo massive actomyosin-controlled membrane flow, which serves to sequester GPIIb-IIIa and makes the platelets refractory to aggregation. We conclude that aggregation requires the formation of long, slender filopodia, probably directed by cytoskeletal rearrangements after activation, and that the transmembrane GPIIb IIIa complex may play a role in signaling these events. PMID- 2207329 TI - Recombinant lipoprotein-associated coagulation inhibitor inhibits tissue thromboplastin-induced intravascular coagulation in the rabbit. AB - Lipoprotein-associated coagulation inhibitor produces feed-back inhibition of tissue factor (tissue thromboplastin)-induced coagulation in the presence of factor Xa Recombinant lipoprotein-associated coagulation inhibitor (rLACI) was tested for its ability to modify thromboplastin-induced intravascular coagulation in a rabbit model that allows monitoring of iodine-125 fibrin accumulation/disappearance in the lung and sampling of blood for the measurement of coagulation parameters. Infusion of thromboplastin into the rabbit caused a rapid increase of radioactivity over the lungs, possibly due to the accumulation of 125I fibrin in the lungs, followed by a rapid decline of radioactivity, suggestive of removal of fibrin from the lungs. Thromboplastin also caused a rapid decrease of systemic fibrinogen that was accompanied by a lengthening of the activated partial thromboplastin time and prothrombin time. The effect of coinfusion of rLACI with thromboplastin or bolus injection of rLACI before thromboplastin infusion was studied. At a high dose of rLACI (800 micrograms/kg body weight), the thromboplastin-induced radioactivity increase in the lungs and the systemic fibrinogen decrease were completely suppressed. The activated partial thromboplastin time and prothrombin time of the plasma samples lengthened, possibly due to the presence of thromboplastin in circulation. The thromboplastin-induced radioactivity increase over the lungs was not completely suppressed by lower doses of rLACI (135 to 270 micrograms/kg body weight), but these doses of rLACI prevented systemic fibrinogen decrease. At a bolus dose of 23 micrograms/kg body weight, rLACI provided 50% protection of the fibrinogen consumption (fibrinogen decreased to 82% compared with 65% in rabbits treated with thromboplastin alone). These results show that rLACI is effective in the inhibition of thromboplastin-induced coagulation in vivo. PMID- 2207331 TI - Effect of recombinant human granulocyte-macrophage colony-stimulating factor administration on the lymphocyte subsets of patients with refractory aplastic anemia. AB - Human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was administered to 14 patients with refractory aplastic anemia (AA). The effect of rhGM-CSF therapy on the lymphocyte phenotype; on the proliferative responses to the mitogen phytohemagglutinin, Candida albicans, and tetanus toxoid antigens; and on the natural killer (NK) activity of the circulating lymphocytes was studied. Samples were collected before (baseline) and twice during the rhGM-CSF administration. The absolute number of circulating lymphocytes remained relatively constant during the first period, but experienced a significant increase (P less than .001) during the second period. The increase was most prominent in the B cells (P less than .001), but the T cells (P less than .016) also increased. Detailed investigation of lymphocyte subsets showed an increase of the markers CD38 (Leu17), HLA-DR, and the transferrin receptor throughout the treatment course giving evidence of lymphoid cell activation. The NK cell activity was suppressed (P less than .008) throughout the treatment. However, proliferative responses to phytohemagglutinin, Candida antigen, and tetanus toxoid were unaffected. Although the mechanism is not yet defined, GM-CSF does induce activation and increase in absolute lymphoid cell number, especially B cells, together with a decrease in NK cytotoxicity. The implication of these immune cell changes in relation to host resistance to microorganisms remains to be established. PMID- 2207332 TI - Abnormalities of the long arm of chromosome 6 in childhood acute lymphoblastic leukemia. AB - To determine the biologic significance of the structural rearrangements of the long arm of chromosome 6(6q) in acute lymphoblastic leukemia (ALL) at diagnosis, we studied 412 consecutive children whose leukemic cell chromosomes had been completely banded and identified 45 (11%) children with this abnormality. The 45 cases were divided into del(6q) only (n = 11), del(6q) and numerical abnormalities (n = 4), del(6q) and structural abnormalities (n = 23), and 6q translocations (n = 7). The breakpoints of del(6q) were subgrouped: del(6)(q15q21) in 11 cases, del(6) (q13q21) in six, del(6)(q21q23) in four, del(6)(q15) in four, del(6)(q15q23) in three, and other deletions in 10 cases. Notably, all these deletions encompassed the 6q21 band, suggesting that this might be the locus of a recessive tumor suppressor gene, the absence of which contributes to malignant transformation or proliferation. Among the seven children with 6q translocations, a previously unidentified nonrandom translocation, t(6;12)(q21;p13) was noted in two cases with an early pre-B immunophenotype. Clinical features and event-free survival were similar among children with or without 6q abnormalities. Overall, children with 6q abnormalities were less likely than those without the abnormality to have a pre-B immunophenotype (P = .03). T-cell immunophenotypes were equally represented in cases with or without 6q abnormalities. However, all four children with del(6q) and a 12p abnormality had early pre-B ALL and all three children with del(6q) and a 9p abnormality had a T-cell immunophenotype. The lack of specificity for a particular immunophenotype may imply that the gene or genes affected by 6q abnormalities are broadly active in the multistep process of lymphoid leukemogenesis. The relatively high frequency of microscopically visible del(6q) indicates the need for molecular studies to identify cases with submicroscopic deletions. PMID- 2207333 TI - Recombinant C5a stimulates transcription rather than translation of interleukin-1 (IL-1) and tumor necrosis factor: translational signal provided by lipopolysaccharide or IL-1 itself. AB - We investigated the effects of recombinant C5a (rC5a) on gene expression and synthesis of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF) in fresh human peripheral blood mononuclear cells (PBMC). Total (cell-associated and secreted) cytokine synthesis was measured. In the strict absence of endotoxin (lipopolysaccharide [LPS]), rC5a resulted in a small but statistically insignificant increase in immunoreactive IL-1 beta and TNF, as well as in IL-1 and IL-6 bioactivity. On the other hand, rC5a induced marked transcriptional activation of IL-1 beta and TNF in a dose-dependent fashion with an optimal concentration of 50 ng/mL. The rC5a-induced cytokine messenger RNA (mRNA) was not spontaneously translated into protein. At 50 ng/mL, rC5a induced the same levels of mRNA for IL-1 beta and TNF as 1 ng/mL of LPS, whereas LPS induced 12 times more IL-1 beta protein and 70 times more TNF protein than rC5a alone. The C5a induced mRNA half-life was the same as that induced by LPS. Formyl-Meth-Leu-Phe (fMLP) did not induce cytokine transcription. Pretreatment with rC5a enhanced cytokine synthesis induced by other stimuli. After 2 hours of preincubation with rC5a, PBMC synthesized 3 to 10 times more IL-1 beta and TNF on subsequent stimulation by LPS or IL-1 itself. We conclude that rC5a provides primarily a transcriptional but not translational signal for IL-1 beta and TNF; the half-life of the untranslated mRNA is the same as that of translated message; rC5a-induced transcription upregulates PBMC for enhanced synthesis of these cytokines; and a translational signal can be provided by LPS or IL-1 itself. PMID- 2207334 TI - The role of cellular maturation in neutrophil heterogeneity. AB - Previous studies have shown that many neutrophil (PMN) characteristics are heterogeneous but the origin of PMN heterogeneity is unknown. It is unclear if PMN functional heterogeneity is secondary to maturational differences or due to distinct subpopulations of cells that possess different functional capacities. The PMN 31D8 antigen is a useful probe for evaluation of PMN subpopulations. The majority of PMNs (approximately 85%) exhibit a high intensity fluorescence after 31D8 monoclonal antibody (MoAb) labeling (31D8 enriched or "bright" PMNs) as determined by flow cytometric analysis. These cells are more functional than cells with low intensity fluorescence (31D8 diminished or "dull" PMNs). Various immunologic, clonogenic and functional techniques were used to study the expression of the 31D8 antigen in HL-60 cells and myeloid cells in order to evaluate antigenic and functional heterogeneity during morphologic maturation. The results of this study indicate that the percentage of 31D8 antigen positive (31D8 antigen enriched and diminished) bone marrow cells increases from 20 +/- 11% in myeloblast cells to 68 +/- 10% in promyelocytes, 93 +/- 2% in myelocytes and 99 +/- 1% in bands and PMNs. 31D8 antigen enriched cells first appear at the myelocyte stage (32 +/- 10%) and increase in bands (52 +/- 13%), marrow PMNs (62 +/- 13%) and peripheral blood PMNs (88 +/- 4%). These data indicate that the heterogeneous expression of 31D8 antigen in PMNs is due, at least in part, to maturational differences within the PMN population and raise the possibility that other heterogeneously expressed PMN characteristics are also maturationally derived. They also suggest that 31D8 antigenic expression may be a more precise indicator of myeloid functional maturation than maturation as identified by cellular morphology. PMID- 2207335 TI - Serum beta 2 microglobulin in solitary plasmocytomata. PMID- 2207336 TI - Alternative BCR/ABL transcripts in chronic myeloid leukemia. PMID- 2207337 TI - More on the origin of the Reed-Sternberg cell. PMID- 2207338 TI - Patterns of internal elastic lamina morphology in the canine common carotid artery. AB - The internal elastic lamina (IEL) of normal canine carotid arteries was examined by scanning electron microscopy in pressure-fixed specimens with intact endothelium. IEL appearance showed a marked variation between animals and was classified into fenestrated sheet, fibrous, and mixed varieties. This interpretation of the apparent morphology was confirmed with transmission electron microscopy. It was clear that IEL fenestrae were associated with surface depressions and that in areas of fibrous IEL there was surface elevation over individual fibres. Within individual animals there was little variation in the pattern of IEL either along or between common carotid arteries. If theories of atherogenesis involving the IEL are correct, the variation of IEL patterns between animals would suggest a corresponding variation of incidence and severity of atheromatous lesions of the common carotid artery between animals. Further, the occurrence of fibrous areas distributed throughout the fenestrated sheet would suggest a focal distribution of lesions along such arteries. PMID- 2207340 TI - 7th international symposium on vascular neuroeffector mechanisms. A satellite symposium of the 11th International Congress of Pharmacology, Amsterdam 1990. Bonn, FRG, July 8-11, 1990. Abstracts. PMID- 2207339 TI - Adenosine A2 receptors mediate cerebral vasodilation in the conscious goat. PMID- 2207341 TI - Marrow transplantation for severe aplastic anemia associated with exposure to quinacrine. AB - Severe aplastic anemia developed in a patient after administration of quinacrine for treatment of discoid lupus erythematosus. Marrow transplantation was performed from an HLA genotypically identical sister after conditioning with cyclophosphamide. Quinacrine which was accumulated in the patient tissues did not interfere with engraftment, suggesting that the drug has no direct cytotoxic effect on hematopoietic stem cells. This study extends our previous observation that severe aplastic anemia acquired after exposure to drugs or toxins can be cured by marrow transplantation. PMID- 2207342 TI - Treatment of refractory multiple myeloma with the vincristine-adriamycin dexamethasone (VAD) regimen. AB - Seventeen patients with advanced refractory multiple myeloma were treated with a 4-day continuous infusion of vincristine and adriamycin in combination with 4-day intermittent high-dose dexamethasone (VAD). Ten patients entered a partial remission (59%). Complete remission was not achieved in any patients. The median response duration was 11 months and the median survival of the responding patients was 18 months versus 5 months for non-responders. Major complications during VAD treatment were infections probably due to a combination of myelosuppression and intensive corticosteroid therapy. The VAD regimen offers a useful chemotherapy that produces an overall high response rate even in intensively pretreated patients resistant to first line therapy. The treatment results in a clear tendency to longer survival in responding patients. PMID- 2207343 TI - Hyperviscosity in HIV infected children--a potential hazard during intravenous immunoglobulin therapy. AB - A four year old boy with symptoms of HIV infection and serum IgG of 53.2 g/l had been treated for 16 months with regular infusions of intravenous immunoglobulin (IV IgG). During one such infusion he developed temporary neurological symptoms and signs suggestive of the hyperviscosity syndrome. Serum relative viscosity was raised at 5.0 (normal range 0.42-2.78). Subsequent IV IgG infusions given at a slower rate have been without adverse reactions. In a study of eight HIV infected children including the index case, and 20 children not infected with HIV, serum relative viscosity was significantly raised in the HIV infected children (p less than 0.01; students t-test). Viscosity correlated with total serum IgG, which was raised in all HIV infected children, and with serum IgM. In HIV infected children with very high levels of serum IgG a slow rate of IV IgG infusion should therefore be chosen due to the possibility of hyperviscosity. PMID- 2207344 TI - Therapeutic strategies in inflammatory breast carcinoma based on prognostic factors. AB - Prognostic factors were identified in a group of 210 patients with inflammatory breast carcinoma (IBC) treated at Institut Gustave Roussy from 1976-1985 with three successive induction protocols: Group A (n = 91), 1976-1980, doxorubicin, vincristine, methotrexate (AVM); Group B (n = 79), 1980-1982, doxorubicin, vincristine, cyclophosphamide, methotrexate, 5-fluorouracil (AVCMF); Group C (n = 40), 1983-1985, AVCMF. Groups A and B received 3 courses of respective chemotherapy (Ct) followed by radiotherapy (Rt), 45 Gy to breast and nodes and 65 70 Gy to the tumor. Group C after the third Ct course received split courses of Rt to equivalent doses so there was no time lag between Ct courses. Ct from fourth to ninth courses was AVM in all groups. Hormonal therapy, radiocastration (pre and perimenopausal) or tamoxifen (postmenopausal) was given all patients. Clinical characteristics of age, menopausal status, castration, N status, and degree of clinical inflammation (limited to tumor area [PEV 2] or involving the entire breast [PEV 3]) were similar in all groups. Groups B and C had identical disease-free and overall survivals, superior to Group A (p = 0.005). In multi variate analysis, AVCMF was one of the important prognostic factors together with PEV and N status.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2207345 TI - Cathepsin D in breast cancer. AB - Cathepsin D is an acidic lysosomal protease present in all cells. In estrogen receptor positive and negative breast cancer cell lines, the mRNA coding for pro cathepsin D is overexpressed and sorting and maturation of the pro-enzyme are altered, leading to accumulation of the active proteinase in large endosomes and to secretion of the precursor (52K protein). In MCF7 cells, the cathepsin D mRNA is induced directly and transcriptionally by estrogens and indirectly by growth factors. In vitro, pro-cathepsin D is an autocrine mitogen on breast cancer cells and can be auto-activated to degrade extracellular matrix and proteoglycans and to activate other proteinases in acidic microenvironments. In patients, there is a significant correlation between high cathepsin D concentrations in the cytosol of primary breast cancer and development of metastasis. This marker is independent of other prognostic factors and appears to be particularly useful in lymph node-negative tumors. These results suggest that overexpression and possible derouting of cathepsin D plays an important role in invasion and metastasis of breast cancer. PMID- 2207346 TI - A breast pre-cancer test? Preliminary results based on a breast temperature rhythm abnormality during the menstrual cycle. AB - This study documents the menstrual thermal cycle of 16 breasts considered at normal risk for breast (8 women) and 15 breasts considered at high risk for breast cancer (i.e. ipsilateral N = 7 or contralateral N = 8 to a previously [locally] excised carcinoma). The surface thermometry studies were carried out for 1 1/2 hours each evening for one menstrual cycle using a special automated instrumentation, the 'Chronobra', with the subject at home. The surface temperatures were adjusted to remove the fluctuations in arterial blood temperature during the menstrual cycle, so that they are thought to represent a breast-specific menstrual rhythm. Across subjects, the cycles were synchronised by the day of the progesterone peak obtained by radioimmunoassay of saliva collected daily. Following ovulation, the normal risk breasts exhibited a steady rise of temperature for 14 days to a well defined peak. In contrast the 'high risk' breasts exhibited a continuous hyperthermia with smaller peaks. Linear discrimination analysis by multiple regression achieved a complete separation of the individual normal and 'high-risk' data sets. The method shows promise for the development of a non-invasive screening test for breast pre-cancer in premenopausal women. PMID- 2207348 TI - Molecular biology and its impact on gastroenterology. PMID- 2207347 TI - Selenium in serum as a possible parameter for assessment of breast disease. AB - The level of selenium in blood serum was determined in 33 patients with breast cancer, 13 women with verified mastopathy, and 43 healthy subjects from the Zagreb area. In the second and third quartiles the values of selenium obtained from sick subjects (41-58 micrograms/L) and healthy subjects (73-89 micrograms/L) differed significantly (P less than 0.001). In the group of subjects with mastopathy, serum selenium in the same way ranged from 67-76 micrograms/L and did not differ significantly from the group of healthy women, but differed significantly from the patients with breast cancer (P less than 0.001). Such a result leads to the conclusion that determination of selenium in the blood could be used as a non-invasive diagnostic parameter in clinical assessment of malignant breast disease. PMID- 2207349 TI - Human immunodeficiency virus and the gastrointestinal tract. AB - Human immunodeficiency virus (HIV) is a retrovirus infecting CD4 positive cells, causing profound immunosuppression and eventually manifesting clinically as the acquired immunodeficiency syndrome (AIDS). The cells principally infected by HIV are T4 (helper) lymphocytes and macrophages. The eventual loss of helper cell function is the prime reason for immunodeficiency, which renders the individual susceptible to opportunistic infections. Virtually every organ system in the body can be affected clinically during the course of HIV infection. The gastrointestinal tract is a major target and the physiological sequelae are an important cause of morbidity and mortality. The pathophysiology of intestinal infection is not yet fully understood but two main mechanisms have been postulated. The first is reduced intestinal immunity resulting in chronic opportunistic infections, which themselves cause altered intestinal function. The second is that HIV per se affects the intestinal mucosa, causing malfunction. The mechanisms by which the latter occurs are controversial but may result from either direct infection of mucosal epithelial cells or from macrophages within the mucosa. Reports have documented the presence of the HIV genome in both epithelial argentochromaffin cells and macrophages. In addition, profound degeneration of intrinsic jejunal autonomic neurones has been demonstrated but the functional significance of such denervation is as yet unknown. The clinical stage of HIV infection at which intestinal mucosal immunity fails is, by definition, when opportunistic infection occurs (that is, clinical progression to stage 4 disease, namely AIDS) but detailed knowledge of the aetiology of intestinal immune failure is lacking. However, protection of intestinal mucosal surfaces with antibodies against HIV, induced by vaccination using the oral or rectal route, is an area of great interest. The major site of entry of HIV is thought to be via the intestinal tract and thus protection of its surfaces may be crucial in preventing infection. PMID- 2207350 TI - Gastrointestinal non-Hodgkin's lymphoma. PMID- 2207351 TI - Hepatitis viruses. PMID- 2207352 TI - Molecular genetics of chronic liver diseases. AB - The molecular genetics of five common single gene and one polygenic chronic liver disease is discussed. In two of the single gene disorders, alpha 1-antitrypsin deficiency and cystic fibrosis, the gene responsible is now known and the repertoire of different mutations underlying the disease is being defined. In the other three single gene defects (haemochromatosis, polycystic liver disease and Wilson's disease) the chromosomal location of the disease allele is known. It is anticipated that recombinant DNA techniques will enable the genes responsible for these diseases to be cloned in the near future, thus allowing the biochemical abnormalities to be defined through reverse genetics. In many chronic liver diseases the relative contribution of genetic and environmental factors remains unclear. Evidence suggests there is a definite genetic component in predisposition to alcoholic cirrhosis; the role of putative candidate genes is discussed. It is hoped that the definition of a genetic locus linked to alcoholic cirrhosis will ultimately teach us more about the basic pathogenesis of this disease. PMID- 2207353 TI - Hereditary fructose intolerance. AB - Hereditary fructose intolerance (HFI) is an inborn error of carbohydrate metabolism that is inherited as an autosomal recessive condition. The disease is caused by a catalytic deficiency of aldolase B and is characterized by severe abdominal symptoms and hypoglycaemia which follow the ingestion of fructose, sucrose or sorbitol. The exact prevalence of HFI in different populations is unknown but studies from Switzerland suggest a disease frequency of about 1 in 20,000 live births, thus predicting a carrier frequency of greater than 1% and a gene prevalence that approaches polymorphic frequency. It is notable that many patients who endure severe symptoms during early infancy develop a marked aversion to harmful foodstuffs and thereby survive to adulthood. Although exposure to fructose may prove to be fatal in this disorder, institution of a strict exclusion diet is curative. HFI, when treated rigorously after diagnosis, is thus compatible with a long and healthy life. HFI vividly illustrates the interplay of dietary factors and heredity in the development of human disease. The recent identification of genetic lesions that cause this disorder further demonstrates the remarkable clinical benefits that may accrue from the study of the molecular basis of inherited diseases and its population genetics: it is now possible to detect asymptomatic disease carriers and diagnose the disorder in affected families by non-invasive analysis of small samples of genomic DNA. Moreover, the systematic investigation of natural mutations in the human gene for aldolase B has allowed regions that are critical for catalytic function of this enzyme to be identified as part of an extended study of its molecular biology. PMID- 2207354 TI - [Is the cytological detection of cervical cancers really useless?]. PMID- 2207355 TI - [Immunocytochemical assay of estrogen receptors in puncture products of breast carcinomas]. AB - In a pilot study, estrogen receptors (ER) were assayed on 42 surgically removed breast tumors by the following 3 methods: biochemical assay with dextran coated charcoal (DCC), Abbott immunoenzymatic (ER-EIA) and immunocytochemical (ER-ICA) technics. DCC and ER-EIA were performed on biopsy specimens while ER-ICA was run on cytocentrifugated cells obtained by fine needle aspiration (FNA). ER contents were expressed according to an index taking into account the proportion of colored neoplastic cells and the intensity of staining. Statistical correlation coefficient (Spearman and Kendall) concordance, sensitivity and specificity between the results were calculated (ER - ICA/ER - EIA: P less than 0.001, r = 0.38, concordance = 83%, sensitivity = 86%, specificity = 77%; ER - ICA/DCC: P less than 0.05, r = 0.22, concordance = 77%, sensitivity = 85%, specificity = 63%; ER - EIA/DCC: P less than 0.001, (r = 0.60). As previously reported, both immunoassays showed good agreement. The weaker but nevertheless significant correlation found with reference DCC may be due to the heterogeneity of tumoral ER content. This hypothesis is supported by the variability of ER - ICA assays on multiple FNA performed in 16 cases from our series. Use of multidirectional FNA slightly improved the results. Nevertheless, ER - ICA appear to be a good semi quantitative method and might be helpful in the follow-up of metastasis treated with anti-estrogen, especially in small lesions not assayable by DCC. PMID- 2207356 TI - [Possible value of variations in the serum alkaline DNAse activity in the prognosis of cancers of the upper respiratory-digestive tract treated by chemotherapy]. AB - Variations in serum alkaline DNase activity before and repeatedly after standardized chemotherapy were examined in patients with head and neck carcinomas. The enzyme activity was measured by way of a modified spectrophotometric method. No variations of such activity observed in patients without therapeutic response or with minor response could be considered as a marker of primary or acquired resistance to chemotherapy. Distinct variations in serum alkaline DNase activity (a steep decrease after therapy followed a few weeks later by a regain of values higher than the initial value) correspond to complete or partial positive responses. Such observations of the variations in enzyme activity in relation to individual initial values measured before therapy could be considered as a reliable prognostic test for the therapy of many head and neck carcinomas. PMID- 2207357 TI - [Tomodensitometric aspects of brain lymphomas: apropos of 19 cases. Brain lymphoma]. AB - The authors present the results of CT studies for 19 patients with cerebral lymphoma (including 12 primary tumors). CT appearances varied considerably, because 5 of the 12 primary lymphomas presented as multifocal lesions, and lesion sites included the corpus callosum (3 cases), the central caudate nucleus (4 cases), the posterior fossa (3 cases), and the cerebral hemispheres (6 cases). These findings are in agreement with literature data. Although a solitary, hyperdense and homogeneous lesion in the corpus callosum or the central caudate nucleus is indicative of cerebral lymphoma, numerous other aspects are possible and owing to the increasing frequency of this pathology should suggest this diagnosis. There is no specific appearance for secondary lymphomas, but diagnosis is often facilitated by concomitant systemic involvement. PMID- 2207359 TI - [Trial of premedication with lorazepam for the prevention of emetic effects of cisplatin]. PMID- 2207360 TI - [Pharmacologic bases of chemotherapy of brain tumors in children]. AB - In terms of pharmacology, drug delivery is an important obstacle in the development of brain tumor chemotherapy. The blood-brain barrier limits the drug penetration in normal brain tissue around the tumor and at distant potential metastatic sites. In the tumor, the altered blood-brain barrier, ie blood-tumor barrier, decreases the drug entry in malignant cells. The knowledge of the blood brain barrier physiology and the definition of the laws that govern the drug delivery to the central nervous system allow the development of new strategies to increase drug delivery to the tumor. In pediatric oncology, the more appropriate methods are the use of anticancer agents that easily cross the blood-brain barrier and the development of high-dose systemic chemotherapy regimens with or without bone marrow rescue. PMID- 2207358 TI - [Echography and computed tomography in the evaluation and follow-up of uterine cancers]. AB - In this review of 139 cancers of the cervix uteri and 43 cancers of the corpus uteri, the authors compare clinical, sonographic and CT data. For the 58 patients with cervical cancer who presented infiltration of the parametrium at physical examination under general anesthesia, sonography gave 11 false negative errors while CT gave 8 false positives. By contrast, for the 47 tumors staged IIb after examination under general anesthesia, sonography disclosed additional abnormalities in 20 cases and CT in 22 cases. A series of 52 disease recurrences in patients who had received curative treatment for uterine cancer was also reviewed; overall, an association of physical examination and ultrasonography had the same value as CT. In light of these results, the authors propose an algorithm for the exploration of uterine cancers in which the results of physical examination condition examination by ultrasonography or CT. PMID- 2207361 TI - [Neurologic complications of brain radiotherapy: contribution of experimental studies]. AB - Cerebral complications of radiotherapy may occur in an acute, early or semi delayed or delayed form. The mechanism of these complications are poorly understood. The main clinical aspects of radiation-induced cerebral damage are reviewed, together with results of experimental studies following cerebral irradiation with conventional doses. PMID- 2207362 TI - [Modern technics of irradiation of brain tumors in children]. AB - Radiotherapy still represents with surgery the cornerstone in the management of pediatric brain tumors. Techniques of irradiation have benefited greatly from modern imaging, CT scan and MRI for tumor-volume delineation, as well as megavoltage equipment, mainly linear accelerators delivering both high-energy X Rays and electrons, widely used in cranial-spinal irradiations. Furthermore, new modalities of doses and volumes have been tested in various tumors (medulloblastomas, germ cell tumors...), in studies frequently combining chemotherapy with conventional therapies. Nevertheless, local control remains a major concern in tumors such as brain stem and high grade supratentorial gliomas. Concerning iatrogenic neurological sequelae, particularly harmful in children, limited data suggest an improvement in recent years. This improvement is partly due to the reduced prophylactic doses for the treatment of medulloblastomas, but further long-term observations are necessary. For these reasons, multiple technical innovations have been investigated. Some of them concern irradiation selectivity: stereotactic pencil beams, interstitial brachytherapy, heavy charged particles, 3-dimensional treatment planning. Others aim to increase the irradiation "efficacy": multifractionation, high LET particles, radiation sensitizers. PMID- 2207363 TI - [Systemic chemotherapy with conventional doses for brain tumors in children: phase II trials]. AB - The analysis of Phase II trials with regard to brain tumors in children, aiming to test the activity of 1 drug or a combination of drugs is not easy, due to the following reasons: poor selection of patients (clinical and pathological heterogeneity), not always rational choice of the drugs and mostly, variability of the criteria and the methods used to assess the tumor response. When using a single drug, the current most efficient agents seem to be: cisplatinum, carboplatin, cyclophosphamide and etoposide, while nitroso-ureas have not been strictly studied. When using polychemotherapy, the best results have been obtained with the "8 drugs in 1 d" regimen. The most chemo-sensitive tumors are: medulloblastomas, primitive neurectodermal tumors, pinealoblastomas; high grade ependymomas and astrocytomas have been studied less in children than in adults. Present and future strict organisation of Phase II trials in brain tumors is compulsory in order to select the active agents, and to establish the best modalities of administration. The need to assess chemotherapy not only in refractory or relapsing patients, but also at diagnosis in high-risk patients is emphasized (after incomplete surgery and before radiotherapy). PMID- 2207364 TI - [Adjuvant treatment of colonic cancer. An important progress?]. PMID- 2207366 TI - [Treatment and prognosis of stomach cancers in the population of the Cote d'Or's District (1976-1985)]. AB - The present study on treatment and prognosis of gastric cancers is based on the data of the digestive tract cancer registry set up for the French department of Cote-d'Or. During the 1976-1985 period, 784 cases of gastric cancer were diagnosed. Resection for cure was performed in 41.3% of gastric cancers and that proportion remained the same during the course of the study period. Operative mortality was 18.5% after resection for cure and 26.7% after palliative surgery. The overall survival rate was 31.7% at 1 year, 17.0% at 3 years, and 13.0% at 5 years. Ten different criteria (personal data, histologic and therapeutic parameters) were studied in relation to survival. With the univariate analysis, the survival rates were related to age, duration of the symptoms, history of previous gastric ulcer, tumour location, stage of diagnosis and treatment. Only 4 aspects were of good prognosis according to the multivariate analysis (Cox model): extension limited to the gastric wall, resection for cure, duration of the symptoms and location to the antrum or the angulus. These results underline the fact that the prognosis of gastric cancer in a well-defined population remains poor. Because of its severity, gastric cancer still represents a major cancer problem. PMID- 2207365 TI - [Combined radiotherapy-chemotherapy in inoperable bronchial carcinoma (small cell carcinoma excluded)]. AB - When treated by irradiation alone, non small cell carcinomas of the lung usually experience a very poor outcome. Consequently, more interest is being focussed on radiotherapy and chemotherapy association. The analysis of a randomized trial comparing irradiation alone to a sequential or an alternated combination of radio and chemotherapy did not reveal any clear advantage of the association of both therapies on each technique used alone. It is only when using concurrent irradiation and chemotherapy that some encouraging results are reported. Several non randomized studies used radio and chemotherapy prior to surgery, aiming at increasing the resectability rate. However, the criteria for initial unresectability were not homogeneous and it is not yet clear if such an association really allowed the state of surgical resection to be improved. In the near future it could be worth considering the use of radiosensitizing drugs, synchroneously given with an irradiation delivered with a multiple daily fractionation. This technique would possibly lead to a therapeutic gain, by increasing the local control rate and reducing the metastasis rate, while keeping it to an acceptable level of toxicity. PMID- 2207367 TI - [Diagnostic value of SCC-TA4 determination in 4 localizations of epidermoid cancers. An experience of the FNCLCC subgroup of radio-analysis]. AB - A multicenter and retrospective study of the diagnosis value of SCC-TA4 in squamous cell carcinomas of 4 localisations was made with the 2 thresholds of 2 and 2.5 ng/ml. However, 3.1% of controls have a SCC value above 2.5 ng/ml. Sixteen benign gynecologic pathologies had no positive level. The benign digestive (N = 73), bronchial (N = 345) pathologies and no squamous cell carcinomas (N = 93, N = 220 respectively), had SCC-TA4 mean levels significantly lower than corresponding squamous cell carcinomas (N = 153, N = 128 respectively). Sensitivity of the test varied from 40% in the squamous cell carcinomas of the lung, to 72% in the squamous cell carcinomas of the uterine cervix. Specificity was always very high and varied from 91% in the SCC of lung, to 100% in the SCC of uterine cervix. For the SCC of uterine cervix, oesophagus and head and neck, the mean values and incidence of positive levels increased significantly with increasing tumor size and advancing disease stage. For the SCC of uterine cervix, mean SCC-TA4 levels and percentages of positive levels above 2 ng/ml were significantly higher for the patients with recurrence (22.5 +/- 4.6 ng/ml; 76%) or with metastasis appearance (23.6 +/- 5.4 ng/ml; 77%) than for the patients in remission (less than 1.5 ng/ml; 0%). In the SCC of oesophagus, we report levels before treatment that are significantly higher for the patients with metastasis at the first attempt (4.2 +/- 5.1 ng/ml; 59%), and an elevated SCC level at the diagnosis evoked a SCC of lung already disseminated (8.8 +/- 12.1 ng/ml; 50%) that will fail to respond to treatment (4.0 +/- 4.2 ng/ml; 48%). PMID- 2207368 TI - [A survey on breast conservation modalities in cancer institutes]. AB - A survey on indications and techniques used in conservative treatment in breast cancer was performed in 19 French cancer centers. A consensus seems to exist about treatment modalities: irradiation techniques, breast dose, indication of chemotherapy. Other points are differently appreciated: exeresis margin, tumor bed dose, boost technique. In spite of these differences, the results obtained seem to be equivalent. PMID- 2207370 TI - [Primary non-Hodgkin's high grade malignant lymphoma of the digestive system. A prospective study of the combination of surgery-chemotherapy-radiotherapy]. AB - We report a prospective study concerning the association of surgery-chemotherapy and radiotherapy in the treatment of primary high grade digestive non-Hodgkin's lymphomas in 19 patients. The analysis of 11 stages IE, 5 stages II1E and 3 stages II2E allowed us to evaluate the efficacy and the tolerance of this triple therapeutic association. Fifteen patients are alive and well with a median follow up of 54 months. One of these patients relapsed, but after autologous bone marrow transplantation is in second unmaintained complete remission. Four patients died of intercurrent aetiology although one death was related to treatment morbidity. Our results and the analysis of literature data lead us to recommend the triple association in the treatment of stage II2E high grade primary digestive lymphomas (PDL) and for PDL without complete resection. However, surgery and chemotherapy appear to be sufficient in the treatment of stages IE and II1E with complete resection. PMID- 2207369 TI - [Phase II trial as 2nd line chemotherapy with 5 fluorouracil and cisplatin (5FU CDDP) for advanced breast cancer]. AB - Thirty patients with advanced breast cancer, previously treated with anthracycline and 5 fluorouracil in bolus administration, were evaluated with a chemotherapy regimen generally used in head and neck cancer. Treatment schedule consisted of: cisplatin 100 mg/m2 on d 1 and 5 fluorouracil 1000 mg/m2 continuous infusion on d 2-3-4-5 every 21 d. With all measurable lesions and 27 evaluable patients, the response rate was 29% (95% confidence interval: 12-47%), with 5 complete responses (3 soft tissue - 2 lung) and 3 partial responses (1 lung - 2 liver). The median duration of response is 4.5 months (range 2-11 months). The 30 patients (93 courses) are evaluable for toxicity. Hematologic toxicity was mild: anemia 68% grade 0, neutropenia 68% grade 0 and thrombocytopenia 83% grade 0. Nausea and vomiting were severe 83% grade 3 + 4 at d 1. Others side effects were mild including 5/91 mucositis grade 2 + 3, peripheral neuropathy 1/31 grade 2 and 2/91 reversible rise in serum creatinine greater than 1.5 mg/dl. PMID- 2207371 TI - Nitrosourea derivatives for the treatment of Hodgkin's disease involving the central nervous system: a study of 23 cases. AB - This study deals with the effectiveness of nitrosourea derivatives (nitrosomethylurea and CCNU) used as single agents or in combination with vinca alkaloids, procarbazine and prednisolone in 23 patients suffering from Hodgkin's disease with spinal cord or intracranial involvement. Complete regression of neurologic symptoms was observed in 61% of patients with spinal cord compression and in 4 out of 5 cases of brain involvement. No relationship was found between type, degree and duration of symptoms, and treatment efficacy. PMID- 2207373 TI - Isolation and characterization of beta-hydroxypropionic acid- and hydroxyacetic acid-uroporphyrin I in the urine of a patient with congenital erythropoietic porphyria by high performance liquid chromatography and liquid secondary ion mass spectrometry. AB - beta-Hydroxypropionic acid- and hydroxyacetic acid-uroporphyrin I have been isolated from the urine of a patient with congenital erythropoietic porphyria by reversed phase high performance liquid chromatography. The compounds were characterized by their chemical behaviour and confirmed by liquid secondary ion mass spectrometry. PMID- 2207372 TI - Determination of individual bile acids in serum by high performance liquid chromatography. AB - A high performance liquid chromatographic (HPLC) method for analysis of 4 free and 8 conjugated bile acids in submicromolar quantities in serum is described using precolumn derivatization with 4-bromomethyl-7-methoxycoumarin (BMC) and fluorescence detection. Bile acids were extracted from serum with 0.4 M sodium bicarbonate, adsorbed onto a Sep-Pak C18 cartridge and eluted with methanol. The extract was derivatized with BMC in acetonitrile using 18-crown-6 crown ether as catalyst and the BMC labelled glycine conjugates and free bile acids were analysed using acetonitrile + methanol + water gradient elution and detection at 320/385 nm. Using a novel and simple approach, taurine conjugates were isolated by extracting the dried, derivatized material with water, in contrast to previous methods which required column chromatography cleanup to isolate the taurine conjugates prior to derivatization. The isolated taurine conjugates were then hydrolysed enzymatically, extracted, derivatized and analysed as free-bile acids. Recoveries of individual bile acids varied from 83-96% for free and glycine conjugates and 72-83% for taurine conjugates. Coefficients of variation were in the range of 5.1-12.5%. In addition to the simpler and shorter procedure for taurine conjugates, this method has increased sensitivity over most other procedures and improved HPLC separation for the various bile acids and conjugates with equivalent recovery and reproducibility compared with other published methods. PMID- 2207374 TI - Determination of 6-mercaptopurine and its metabolites in plasma or serum by high performance liquid chromatography. AB - A sensitive and accurate reversed phase liquid chromatographic assay was developed for the determination of 6-mercaptopurine (6MP) (the active metabolite of azathioprine) in human plasma. The assay involved extraction into acetonitrile and dichloromethane from plasma pretreated with 0.038 M of dithiothreitol solution. The residue was analyzed by isocratic chromatography on a C18 analytical column with UV detection at 326 nm. The average extraction recovery of 6MP was 85%. The method has been applied successfully to the determination of 6MP and its metabolites in pharmacokinetic studies. PMID- 2207375 TI - Separation of the Hageman factor fragment from human serum albumin by chromatography on blue sepharose CL-6B. AB - The separation of the Hageman factor fragment (HFf) activity from human serum albumin by chromatography on Blue Sepharose CL-6B is described. The complete separation cannot be achieved in a single chromatography step due to complex formation between HFf and albumin. PMID- 2207376 TI - High performance liquid chromatography determination of doxorubicin and daunorubicin in plasma using UV detection and column switching. AB - A method for the determination of doxorubicin and daunorubicin in plasma is described. The plasma is injected directly into a loop column and then washed with water. After switching the injection valve, the sample is separated on a phenyl column using detection at 254 nm. The detection limit is 10 ng/mL, the coefficient of variation is 7% for 100 ng/mL of doxorubicin and 4% for 200 ng/mL of daunorubicin. PMID- 2207377 TI - Chiral separation and determination of propranolol enantiomers in rat or mouse blood and tissue by column switching high performance liquid chromatography with ovomucoid bonded stationary phase. AB - Resolution of propranolol (PL) enantiomers in biological samples was accomplished by column switching high performance liquid chromatography using a short precolumn and an analytical column of ovomucoid chiral phase. Plasma, whole blood or tissue homogenate sample was directly injected into the precolumn, and PL was adsorbed on Butyl Toyopearl 650-M. After column switching, the PL was backflushed and transferred to the analytical column (Ultron ES-OVM) by the eluant. Fluorometric detection was carried out at lambda ex = 297 nm and lambda em = 340 nm with a detection limit of 0.5 pmol (signal to noise ratio = 2). The recovery (98.8-103%), reproducibility (coefficient of variance less than 3%) and enantiomer resolution (separation factor 1.15) were satisfactory using as eluant 50 mM sodium dihydrogenphosphate (pH 4.6) containing 12% ethanol. The time course of elimination of PL enantiomers in rat or mouse blood and tissues was also studied. PMID- 2207378 TI - Isocratic reversed phase high performance liquid chromatography determination of twelve natural corticosteroids in serum with on-line ultraviolet and fluorescence detection. AB - An isocratic reversed phase high performance liquid chromatography procedure utilizing ultraviolet and fluorescence detectors linked in series is described for the analysis of cortisone (E), cortisol (F), corticosterone (B), 11 deoxycortisol (S), 11-deoxycorticosterone (DOC), androstenedione (A), testosterone (T), 17-hydroxyprogesterone (17-OHP), progesterone (P), estriol, estradiol, estrone, prednisone acetate and dexamethasone acetate in serum. Serum specimens were extracted with ethyl ether. The optimized mobile phase was methanol + tetrahydrofuran + water (26:18:56, v/v/v). A Shim-pack ODS column was used. The recoveries were 80 to 103%. Intra- and inter-day coefficient of variance were less than 8%. The detection limit is 0.5 pmol per injection volume for estriol, estradiol, E, F and B; 1 pmol for S, A, DOC and estrone; 2 pmol for T and 17-OHP; and 4 pmol for P. Serum from normal subjects and patients with congenital adrenal hyperplasia due to 21- or 17-hydroxylase deficiency were measured, as well as samples of maternal and umbilical cord serum. PMID- 2207379 TI - Studies on the determination and degradation of pyrimethamine in mammals. AB - Treatment of pyrimethamine with blood plasma in vitro yields a metabolite which is also produced when the drug is administered through intravenous injection in the rat. A thin layer liquid chromatographic method for quantitative and qualitative determination of pyrimethamine and its metabolite in plasma and biological tissues is described. PMID- 2207380 TI - Analysis of lorazepam in rat brain using liquid/liquid and solid-phase extraction in combination with high performance liquid chromatography. AB - A method for the determination of lorazepam in rat brain is described using liquid/liquid and solid-phase extraction, followed by high performance liquid chromatography. After addition of chlordiazepoxide as the internal standard, 100 mg brain tissue was homogenized and incubated with alkaline protease. Lorazepam and chlordiazepoxide were extracted three times with toluene. After treatment through a C18-Bond Elut column, lorazepam and chlordiazepoxide were analyzed isocratically on a reversed-phase column with a mobile phase consisting of methanol +0.025 M sodium phosphate buffer (66:34, v/v). The eluted drugs were monitored by their absorption at 240 nm. The sensitivity limit of this method was 10 ng of lorazepam per 100 mg of brain tissue sample. The standard curve was linear over the range of 20 to 200 ng lorazepam. The coefficient of variation for day-to-day precision established by 21 replicate analyses was 4.5 to 13.6%. PMID- 2207382 TI - High performance liquid chromatographic assay of Amicar, epsilon-aminocaproic acid, in plasma and urine after pre-column derivatization with o-phthalaldehyde for fluorescence detection. AB - A simple, reliable and highly sensitive procedure was devised for measuring the levels of Amicar in blood and urine. 100 microL of serum or urine sample was added to 10 microL of a 10% w/v zinc sulfate solution and 100 microL of methanol, as previously described (Lam et al., 1980) for the removal of proteins by precipitation. 50 microL of the supernatant was then mixed with 300 microL of 1 M borate buffer containing D-valine as the internal standard before derivatization with o-phthalaldehyde. The amino acids were then separated by a stereoselective reversed-phase system using a mobile phase containing 10% of acetonitrile in 2.5 mM Cu(II) complexes of L-proline. The chromatography is highly selective, resolving Amicar from L-valine which in turn is resolved from its unnatural D antipode, the internal standard. The procedure including sample preparation and separation required a total of 15 min. As little as 50 ng/mL of Amicar in body fluids could be detected as the o-phthalaldehyde derivative by fluorescence. PMID- 2207381 TI - Identification of 17-hydroxyprogesterone and other steroid hormones in saliva from a normal child and patients with congenital adrenal hyperplasia by plasmaspray liquid chromatography/mass spectrometry. AB - A very sensitive, selective and simultaneous method for the analysis of salivary steroid hormones was examined by discharge-assisted thermospray liquid chromatography mass spectrometry (plasmaspray LC/MS). Plasmaspray LC/MS gave [M + H]+ or [MH - H2O]+ as a predominant ion in most of the steroids in this work and in some cases fragment ions were also observed. Eight salivary steroid hormones, pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone, 11 deoxycortisol, cortisol, aldosterone, and testosterone were identified within 10 minutes using the selected ion monitoring technique in conjunction with plasmaspray LC/MS. Progesterone, 17-hydroxyprogesterone, cortisol, aldosterone and testosterone were detected in 1 mL of saliva from a normal child and two patients with congenital adrenal hyperplasia. PMID- 2207383 TI - Making it in urban medicine: a career in the age of scientific medicine. PMID- 2207384 TI - Blood and soil: the serology of the Aryan racial state. PMID- 2207385 TI - "A house of cure": the antebellum South Carolina lunatic asylum. PMID- 2207386 TI - On measuring sex hormones: the role of biological assays in sexualizing chemical substances. PMID- 2207387 TI - Pioneering in family-centered maternity and infant care: Edith B. Jackson and the Yale rooming-in research project. PMID- 2207388 TI - Gas chromatography/negative ion chemical ionization/tandem mass spectrometric quantification of indomethacin in plasma and synovial fluid. AB - A procedure for the quantification of sub-nanogram per millilitre concentrations of indomethacin in plasma and synovial fluid has been developed using gas chromatography/negative ion chemical ionization/tandem mass spectrometry. The procedure is based on selected ion monitoring of the daughter ion at m/z 312 generated following decarboxylation of the 35Cl isotope peak of the indomethacin anion (m/z 356) formed from the pentafluorobenzyl ester of indomethacin in the ion source of the mass spectrometer. The internal standard, d2-indomethacin, has a daughter ion at m/z 316 formed from the corresponding 37Cl isotope peak. The limit of quantification was 0.1 ng ml-1 for both plasma and synovial fluid. PMID- 2207389 TI - Preparation and tandem mass spectrometric analyses of deuterium-labeled cysteine containing leukotrienes. AB - Leukotrienes (LT) C4, E4 and N-acetyl-E4, their respective monomethyl esters and 14,15-2H2 analogs have been synthesized. The collisionally activated decompositions of the [M + H]+ and [M - H]- ions formed by fast atom bombardment (FAB) have been studied by tandem mass spectrometry using a hybrid sector/quadrupole instrument. Structurally informative product ion spectra were obtained for each analyte; the fragmentation pathways proposed are consistent with the parallel data obtained for labeled and derivatized species. Fragmentation of [M + H]+ ions occurs prominently via cleavage of the thioether linkage with charge retention on the cysteine-containing (predominant for LTC4) or lipid-derived (predominant for LTE4) moieties. More pronounced differences were observed between the fragmentations of [M - H]- ions derived from LTC4 and LTE4; the preference for charge retention, however, parallels that observed for the fragmentation of [M + H]+ ions. Selected ion monitoring during continuous flow FAB mass spectrometric analysis of authentic LTC4 indicated a low-picogram detection limit. PMID- 2207390 TI - An improved chemical ionization assay for mevalonic acid. AB - The determination of mevalonic acid by gas chromatography/mass spectrometry (GC/MS) is complicated by poor extractability and multiple product formation. Reliable quantification down to physiological levels was achieved by isolating mevalonic acid by liquid partition chromatography and quantifying the underivatized lactone by means of ammonia chemical ionization, selected ion monitoring, capillary GC/MS. (2H3)mevalonic acid served as the internal standard. The method appears to be suitable for the study of mevalonic aciduria as well as the evaluation of different therapeutic regimens in patients with hypercholesterolaemia. PMID- 2207391 TI - Cell proliferation within the growth plate of long bones assessed by bromodeoxyuridine uptake and its relationship to glucose 6-phosphate dehydrogenase activity. AB - Bromodeoxyuridine (BrdUrd) was incorporated into the DNA of proliferating chondrocytes of the tibiae and metatarsal growth plate of rats of differing ages. Immunodetection of the incorporated BrdUrd was achieved using a monoclonal antibody to BrdUrd and indirect immunofluorescence procedures. The labelling index within the growth plate was found to decrease with advancing age in the tibia and metatarsal. Glucose 6-phosphate dehydrogenase (G6PD) activity appeared to be related to chondrocyte proliferation as a significant correlation was observed between G6PD activity and the labelling index of the tibial chondrocytes. The results of this study indicate that G6PD activity is a possible marker for cartilage growth and also that the BrdUrd technique has several advantages over the conventional autoradiographic methods for the assessment of cell replication. PMID- 2207392 TI - Plasma osteocalcin concentrations in cattle under various pathophysiological conditions. AB - Plasma osteocalcin (BGP) concentrations were measured using an homologous radioimmunoassay in plasma samples (n = 6-14 per group) from fetal and newborn calves, 16-month-old heifers and bulls, and pregnant lactating cows. The highest values (nM) (62 +/- 3) were measured in fetal calves and the lowest (15 +/- 3) in 9-year-old pregnant and lactating cows. No significant relationship could be demonstrated between plasma BGP and somatomedin C, or 1,25(OH)2D or calcium concentrations. In eight normally calving cows, parturition was followed by a progressive increase in plasma BGP concentration, maximum 3 days after calving. It returned to prepartum values 10 days later. In six parturient hypocalcaemic and paretic cows, hypocalcaemia occurring within 12 h following calving was associated with a prompt and very transient increase in plasma BGP concentrations. These results indicate that osteocalcin might play a role in the regulation of bone metabolism in cattle. PMID- 2207393 TI - The relationship of 1,25-dihydroxyvitamin D and radial bone mass. AB - We assessed the association between radial bone mass and vitamin D considering age, estrogen sufficiency and thiazide use in 373 women, aged 20-80 years in a geographically defined area. We measured cortical bone mass of the radius, using photon absorptiometry, and serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, using preliminary chromatography and protein-binding assay. We found that 1,25 dihydroxyvitamin D levels were higher in premenopausal women and postmenopausal women using estrogen replacement as compared to postmenopausal women (P less than 0.02). Users of thiazide-based antihypertensive medications had significantly lower 1,25-dihydroxyvitamin D than their age-matched peers (P less than 0.02). Dietary calcium intake was negatively associated with 1,25-dihydroxyvitamin D levels. Estimates of vitamin D intake from diet or sunlight were not associated with 1,25-dihydroxyvitamin D levels; nor were levels of 1,25-dihydroxyvitamin D related to 25-hydroxyvitamin D levels. 1,25-Dihydroxyvitamin D was negatively and significantly associated with radial bone mass, contributing approximately 6% of the explained variability of bone mass measurements. Together age, body size, thiazide use and 1,25-dihydroxyvitamin D accounted for about 47% of the explained variability in radial bone mass measurement. 1,25-Dihydroxyvitamin D was not associated with bone mass in women currently using a thiazide medication. PMID- 2207394 TI - Calcitonin in Ghanaians and Israelis. AB - Calcitonin (CT) in serum was measured in a group of (black) Ghanaian traumatic fracture patients (GFP) and in two healthy control groups, (black) Ghanaian (GMS) and (white) Israeli (IMS) medical students. CT (mean +/- SD) in GFP, GMS and IMS was, respectively, 17.2 +/- 6.4, 15.5 +/- 2.8 and 7.6 +/- 3.3 pmol/l. The mean difference between the GFP and GMS was not significant, but that between the Ghanaian groups combined and IMS was 8.8 pmol/l, 95% CI 4.1-13.7, P less than 0.001. Observations elsewhere that CT levels in adult blacks in the tropics are higher than those in whites are confirmed. PMID- 2207395 TI - Biology of bone endothelial cells. AB - Cultured endothelial cells are used as tools to study the involvement of endothelium in various physiological and pathological processes. Significant physiological differences exist among endothelial cells from different districts. Microvascular endothelium is an integral part of bone tissue. Bone endothelial cells have been cloned from fetal bovine sternum. They show differentiated characteristics and a novel response to parathyroid hormone. This 'in vitro' model will make possible the analysis of possible influences of the endothelium on bone formation and resorption. The possibility that bone endothelial cells actively participate in the bone remodelling process is proposed. PMID- 2207396 TI - Three types of erythromelalgia. PMID- 2207397 TI - General practitioners' workload. PMID- 2207398 TI - Threat of unemployment and cardiovascular risk factors: longitudinal study of quality of sleep and serum cholesterol concentrations in men threatened with redundancy. AB - OBJECTIVE: To assess whether the threat of unemployment affects risk factors for cardiovascular disease. DESIGN: Longitudinal study of a cohort of middle aged shipyard workers followed up for a mean of 6.2 (SD 1.9) years and a group of controls observed for the same period. The first investigation took place during a period of relative economic stability for the shipyard and the second during the phase of its closure. SETTING: An age cohort health screening programme in Malmo, Sweden. PARTICIPANTS: 715 Male shipyard workers and 261 age matched male controls. MAIN OUTCOME MEASURES: Changes in 19 variables related to the risk of cardiovascular disease, and psychological variables, alcohol consumption, smoking, and dietary habits as assessed by questionnaire. RESULTS: Serum cholesterol concentrations increased more (mean 0.25 (SD 0.68) mmol/l v 0.08 (0.66) mmol/l) and serum calcium concentrations decreased less (-0.06 (0.10) mmol/l v -0.08 (0.09) mmol/l) in the shipyard workers than in the controls. A correlation was found between scores for sleep disturbance and changes in serum cholesterol concentration. In the whole series there was a greater increase in serum cholesterol concentrations among men threatened with unemployment (437/976; 44.8%) than among those who were not. In stepwise regression analysis the change in serum cholesterol concentration was correlated with changes in haemoglobin concentration, body weight, and serum triglyceride and calcium concentrations. A positive correlation was found between change in cholesterol concentration and change in blood pressure, indicating that the overall risk profile had worsened among men with increased serum cholesterol concentrations. CONCLUSIONS: Risk of unemployment increases the serum cholesterol concentration in middle aged men, the increase being more pronounced in those with sleep disturbance. The increase in serum cholesterol is related to changes in other established risk factors for cardiovascular disease. These findings might partly explain the excessive mortality due to cardiovascular disease recorded among the unemployed and people with sleep disturbance. PMID- 2207400 TI - Referral letters and replies from orthopaedic departments: opportunities missed. AB - OBJECTIVE: To study delays between sending referral letters and the outpatient appointment and to assess the content of referral and reply letters, their educational value, and the extent to which questions asked are answered by reply letters. DESIGN: Retrospective review of referrals to 16 consultant orthopaedic surgeons at five hospitals, comprising 288 referral letters with corresponding replies, by scoring contents of letters. SETTING: Orthopaedic teaching hospitals in Nottingham, Derby, and Mansfield. MAIN OUTCOME MEASURES: Weighted scores of contents of referral and reply letters, assessment of their educational value, and responses to questions in referral letters. RESULTS: Median outpatient delay was 23.4 weeks. There was no significant decrease in waiting time if the referral letter was marked "urgent" but a significantly greater delay (p less than 0.01) if referrals were directed to an unnamed consultant. The content score was generally unsatisfactory for both referrals and replies, and there was no correlation for the content scores of the referral letter and its reply (r = 0.13). Items of education were rare in the referral letters (8/288; 3%) and significantly more common in replies (75/288; 26%) (p much less than 0.001). Senior registrars were significantly more likely to attempt education than other writers (p less than 0.02). Education in replies was significantly related to increased length of the letter (p less than 0.05) and was more likely to occur if the referral was addressed to a named consultant (p less than 0.03). 48 (17%) Referral letters asked questions, of which 21 (44%) received a reply. No factor was found to influence the asking of or replying to questions. CONCLUSIONS: The potential for useful communication in the referral letter and in the reply from orthopaedic surgeons is being missed at a number of levels. The content is often poor, the level of mutual education is low, and the use of the referral letter to determine urgency is deficient. Most questions asked by general practitioners are not answered. PMID- 2207399 TI - Comparison of chloroquine, pyrimethamine and sulfadoxine, and chlorproguanil and dapsone as treatment for falciparum malaria in pregnant and non-pregnant women, Kakamega District, Kenya. AB - OBJECTIVE: To compare treatment and protection against falciparum malaria in pregnant and non-pregnant women with three drug regimens. DESIGN: Prospective intervention study with six weeks' follow up. Patients received one of three drug regimens in order of entry. SETTING: Primary care hospital and secondary girls' school in rural western Kenya. PATIENTS: 158 of 988 pregnant women (89 primigravid and 69 multigravid) in the third trimester and 105 of 1488 non pregnant schoolgirls of reproductive age were parasitaemic (more than 500 asexual forms/microliter. These women were divided into three treatment groups by gravid state. INTERVENTIONS: Women were treated with chloroquine base 25 mg/kg over three days or pyrimethamine 75 mg and sulfadoxine 1500 mg as a single dose or chlorproguanil 1.2 mg/kg and dapsone 2.4 mg/kg as a single dose. MAIN OUTCOME MEASURES: Parasitaemia and haemoglobin concentrations measured at seven day intervals for six weeks. RESULTS: Primigravid women were more likely to be parasitaemic on follow up than multigravidas or nulligravidas, whose response was about the same. Parasites did not clear by day 7 in primigravidas in six (20%) of 30 who received chloroquine, three (8%) of 35 treated with pyrimethamine and sulfadoxine, and none of 23 treated with chlorproguanil and dapsone. At day 28, 83%, 19%, and 67% of primigravidas in these treatment groups were parasitaemic. Haemoglobin concentrations rose in all women, but improvement was sustained only in women who remained free of parasites. CONCLUSIONS: Clearance of parasites was better with either pyrimethamine and sulfadoxine or chlorproguanil and dapsone than with chloroquine. Longest protection was obtained with pyrimethamine and sulfadoxine. PMID- 2207401 TI - Adrenaline and nocturnal asthma. AB - OBJECTIVE: To determine whether the nocturnal fall in plasma adrenaline is a cause of nocturnal asthma. DESIGN: Double blind placebo controlled cross-over study. In the first experiment the nocturnal fall in plasma adrenaline at 4 am was corrected in 10 asthmatic subjects with an infusion of adrenaline after parasympathetic blockade with 30 micrograms/kg intravenous atropine. In the second experiment 11 asthmatic subjects showing similar variations in peak expiratory flow rate had the nocturnal fall in plasma adrenaline corrected by infusion before atropine was given. PATIENTS: Asthmatic subjects with a diurnal variation in home peak expiratory flow rate of greater than 20% for at least 75% of the time in the two weeks before the study. MAIN OUTCOME MEASURES: Peak expiratory flow rate and plasma adrenaline. RESULTS: Correction of the nocturnal fall in plasma adrenaline at 4 am to resting 4 pm levels did not alter peak expiratory flow rate either before or after parasympathetic blockade with atropine. CONCLUSION: A nighttime fall in plasma adrenaline is not a cause of nocturnal asthma. PMID- 2207402 TI - Effect of erythropoietin on anaemia in patients with myeloma receiving haemodialysis. PMID- 2207404 TI - What future for the Department of Health? PMID- 2207403 TI - Rectal examination in general practice. AB - OBJECTIVE: To investigate factors influencing a general practitioner's decision to do a rectal examination in patients with anorectal or urinary symptoms. DESIGN: Postal questionnaire survey. SETTING: General practices in inner London and Devon. SUBJECTS: 859 General practitioners, 609 (71%) of whom returned the questionnaire. MAIN OUTCOME MEASURES: Number of rectal examinations done each month; the indication score, derived from answers to a question asking whether the respondent would do a rectal examination for various symptoms; and the confidence score, which indicated the respondent's confidence in the diagnosis made on rectal examination. RESULTS: 279 General practitioners did five or fewer rectal examinations each month and 96 did more than 10 each month. Factors significantly associated with doing fewer rectal examinations were a small partnership and being a female general practitioner, and the expectation that the examination would be repeated. Lack of time in the surgery, and a waiting time of less than two weeks for an urgent outpatient appointment were also important. General practitioners were deterred from doing rectal examinations by reluctance of the patient (278), the expectation that the examination would be repeated (141), and lack of time (123) or a chaperone (39). Confidence in diagnosis was significantly associated with doing more rectal examinations, the perception of having been well taught to do a rectal examination at medical school, and being a male general practitioner. CONCLUSIONS: Factors other than clinical judgment influence the frequency of rectal examination in general practice. Rectal examination may become commoner with the trend towards larger group practices and if diagnostic confidence is increased and greater emphasis put on rectal examination in undergraduate and postgraduate teaching. PMID- 2207405 TI - ABC of major trauma. Trauma of the upper urinary tract. PMID- 2207406 TI - Interpretation and management of PACT (prescribing analysis and cost) data on formularies. PMID- 2207407 TI - Bedding and sleeping position in the sudden infant death syndrome. PMID- 2207408 TI - Bleeding time in patients with hepatic cirrhosis. PMID- 2207409 TI - Methaemoglobinaemia in children treated with prilocaine-lignocaine cream. PMID- 2207410 TI - Colles' fracture. PMID- 2207411 TI - Safety of horseriding. PMID- 2207412 TI - Children with diabetes. PMID- 2207413 TI - Shoulder pain in the elderly. PMID- 2207414 TI - Low level exposure to lead. PMID- 2207415 TI - Training for care assistants. PMID- 2207416 TI - Early detection of gastric cancer. AB - OBJECTIVE: To see whether investigation of dyspeptic patients aged over 40 after their first consultation with the general practitioner would increase the proportions with early and operable gastric cancers. DESIGN: Prospective study of gastric cancer in dyspeptic patients aged over 40 from a defined population. SETTING: 10 General practices (six in central Birmingham, four in Sandwell); the Queen Elizabeth Hospital, Birmingham; and Sandwell District General Hospital. PATIENTS: 2659 Patients aged 40 or over referred with dyspepsia. MAIN OUTCOME MEASURE: Increase in early and operable gastric cancers detected in middle aged patients with dyspepsia. RESULTS: Disease was identified in 1992 patients (75%). Fifty seven were found to have gastric cancer, 36 being treated by potentially curative resection, including 15 with early cancer. CONCLUSIONS: The investigation of dyspeptic patients over 40 at first attendance can increase the proportion of early gastric cancers detected to 26% and the proportion of operable cases to 63%. Such a policy has the potential to reduce mortality from gastric cancer in the population. PMID- 2207417 TI - Menstrual state and exercise as determinants of spinal trabecular bone density in female athletes. AB - OBJECTIVE: To study the effects of amenorrhoea and intensive back exercise on the bone mineral density of the lumbar spine in female athletes. DESIGN: Cross sectional study comparing amenorrhoeic with eumenorrhoeic athletes and rowers with non-rowers. SETTING: The British Olympic Medical Centre, Northwick Park Hospital. PATIENTS: 46 Elite female athletes comprising 19 rowers, 18 runners, and nine dancers, of whom 25 were amenorrhoeic and 21 eumenorrhoeic. MAIN OUTCOME MEASURE: Trabecular bone mineral density of the lumbar spine measured by computed tomography. RESULTS: Mean trabecular bone mineral density was 42 mg/cm3 (95% confidence interval 22 to 62 mg/cm3) lower in the amenorrhoeic than the eumenorrhoeic athletes; this difference was highly significant (p = 0.0002). Mean trabecular bone mineral density was 21 mg/cm3 (1 to 41 mg/cm3) lower in the non rowers than the rowers; this was also significant (p = 0.05). There was no interaction between these two effects (p = 0.28). CONCLUSION: The effect of intensive exercise on the lumbar spine partially compensates for the adverse effect of amenorrhoea on spinal trabecular bone density. PMID- 2207419 TI - Efficacy of potassium and magnesium in essential hypertension: a double-blind, placebo controlled, crossover study. AB - OBJECTIVE: To evaluate the antihypertensive activity of potassium given alone or in combination with magnesium in patients with mild hypertension. DESIGN: A double blind, randomised, placebo controlled, crossover trial of 32 weeks' duration. SETTINGS: Cardiology outpatient department, Sassoon General Hospitals, Pune, India. PATIENTS: 37 Adults with mild hypertension (diastolic blood pressure less than 110 mm Hg). INTERVENTION: Patients received either placebo or potassium 60 mmol/day alone or in combination with magnesium 20 mmol/day in a crossover design. No other drug treatment was allowed. MEASUREMENTS: Blood pressure and heart rate assessed at weekly intervals and biochemical parameters at monthly intervals. RESULTS: Potassium alone or in combination with magnesium produced a significant reduction in systolic and diastolic blood pressures (p less than 0.001) and a significant reduction in serum cholesterol concentration (p less than 0.05); other biochemical variables did not change. Magnesium did not have an additional effect. Urinary potassium excretion increased significantly in the groups who received potassium alone or in combination with magnesium. The drug was well tolerated and compliance was satisfactory. CONCLUSION: Potassium 60 mmol/day lowers arterial blood pressure in patients with mild hypertension. Giving magnesium as well has no added advantage. PMID- 2207420 TI - Transmission of hepatitis B virus by blood transfusion in Yaounde, Cameroon. PMID- 2207418 TI - Prevalence of HIV antibody and pregnancy in Tayside, 1984-9: background to screening. AB - OBJECTIVE: To determine age specific prevalence of HIV antibody, incidence of pregnancy, and likelihood of detection and correct assignment to risk category by antenatal screening of women known to be positive for HIV antibody, from 1984 to 1989. DESIGN: Retrospective analysis of reproductive history and risk behaviour of women positive for HIV antibody and prediction of detection by screening on the basis of blood group samples, Guthrie tests, and rubella tests. SETTING: City of Dundee, where the prevalence of HIV is high, since the appearance of HIV in 1984, predominantly among heterosexual intravenous drug users. PATIENTS: All (61) women known to be positive for HIV antibody who had had clinically indicated tests, for whom case notes were available for 60. MAIN OUTCOME MEASURES: Risk assessment according to case notes and reported to the laboratory, incidence of infection, geographical location, age, date of positive test result, and reproductive history. RESULTS: With 61 infected women the overall minimum prevalence among women within the city of Dundee was 0.67/1000 and 2.9/1000 among women in their third decade. Of the 60 women whose reproductive history was available, 35 had 57 pregnancies, 36 of which occurred after seroconversion was known to have taken place, representing 8.7% of the total number of affected pregnancies reported for the United Kingdom. If antenatal screening for HIV had been performed between 1984 and 1989 it could not have detected positivity for HIV antibody in 25 (42%) women who had no pregnancies during this time. Among the remaining 35 women, screening samples taken for blood grouping could have identified a maximum of 34 (57%), samples taken to check rubella susceptibility a maximum of 22 (37%), and blood spots on Guthrie cards a maximum of 19 (32%). Retesting would have occurred in 14 women 33 times with samples taken for blood grouping, but three and four women would have been tested twice using samples taken for rubella testing and Guthrie cards respectively. Anonymous screening would have been unable to determine risk category as a history of intravenous drug use was known in 47 (79%) women before testing but this was increased by a further 5 (8%) who admitted to it after the test result was known. CONCLUSION: Interpreting the results of antenatal screening programmes will be complex and will underestimate overall prevalence of HIV antibody among women; this will be exaggerated by strategies based on anonymous testing with Guthrie cards or on samples taken for rubella testing, which do not include women who have had an earlier loss of pregnancy. Only open testing with consent will permit satisfactory attribution to PMID- 2207421 TI - Aetiological importance of ovulation in epithelial ovarian cancer: a population based study. PMID- 2207422 TI - Risk of HIV infection among clients of the sex industry in Scotland. PMID- 2207423 TI - What did audit achieve? Lessons from preliminary evaluation of a year's medical audit. AB - OBJECTIVE: To evaluate the experience of a year's audit of care of medical inpatients. DESIGN: Audit of physicians by monthly review of two randomly selected sets of patients' notes by 12 reviewers using a detailed questionnaire dedicated to standards of medical records and to clinical management. Data were entered into a database and summary statistics presented quarterly at audit meetings. Assessment by improvement in questionnaire scores and by interviewing physicians. SETTING: 1 District general hospital. PARTICIPANTS: About 40 consultant physicians, senior registrars, and junior staff dealing with 140 inpatient records. MAIN OUTCOME MEASURES: Median scores (range 1 to 9) for each item in the questionnaire; two sets of notes were discussed monthly at "general" audit meetings and clinical management of selected common conditions at separate monthly meetings. RESULTS: A significant overall increase in median scores for questions on record keeping occurred after the start of the audit (p less than 0.01), but interobserver variation was high. The parallel audit meetings on clinical management proved to be more successful than the general audits in auditing medical care and were also considered to be more useful by junior staff. CONCLUSIONS AND ACTION: Medical audit apparently resulted in appreciable improvements in aspects of care such as clerking and record keeping. Analysis of the scores of the general audits has led to the introduction of agreed standards that can be objectively measured and are being used in a further audit, and from the results of the audits of clinical management have been developed explicit guidelines, which are being further developed for criterion based audit. PMID- 2207424 TI - How easy is it to contact the duty medical doctor responsible for acute admissions? AB - OBJECTIVE: To ascertain ease or difficulty of contacting duty junior doctors responsible for acute medical admissions by telephone. DESIGN: Telephone survey of hospitals in six health regions in England and Wales. SETTING: 70 Randomly selected hospitals, 15 of which were excluded because of non-acceptance of acute medical admissions. PARTICIPANTS: 71 Duty doctors (duty house physicians, senior house officers, or registrars responsible for acute medical admissions) in 48 hospitals; seven duty doctors in seven hospitals were excluded (four declined to participate and three required a written explanation of the survey). 67 Doctors gave full information to all questions. MAIN OUTCOME MEASURES: Time taken for hospital switchboards and duty doctors to reply to telephone call, diagnoses of patients recently admitted, and on call rotas and hours of sleep of duty doctors. RESULTS: Hospital switchboards responded within 30 seconds in 87 (74%) calls, and in 76 calls (64%) the duty doctor requested was contacted within a further two minutes. Chest pain, possibly due to myocardial infarction, was the most common reason for acute medical admissions. Nearly half (48%) of the duty doctors in larger hospitals reported having 4-5 hours sleep or less on their nights on call. Most (30) were on a one in three rota; two were on a one in two rota. CONCLUSIONS: Despite impressions to the contrary contacting the duty medical team by telephone seemed fairly easy. Although most junior doctors were on a rota of one in three or better, insufficient recognition may be given to their deprivation of sleep during nights on duty. PMID- 2207425 TI - Variations in hospital admissions and the appropriateness of care: American preoccupations? PMID- 2207426 TI - Renal replacement treatment for diabetic patients in Newcastle upon Tyne and the Northern region, 1964-88. AB - OBJECTIVES: To review the experience of renal replacement treatment in diabetic patients treated in Newcastle upon Tyne and the Northern region from 1964 to 1988, and to compare the morbidity and mortality of diabetic patients treated with dialysis or transplantation with those of matched controls of non-diabetic patients. DESIGN: Retrospective study of clinical case notes. SETTING: Renal units of the Northern region, particularly that in Newcastle upon Tyne. PATIENTS: All 65 diabetic patients treated by renal replacement treatment in Newcastle upon Tyne from 1964 to 1987; 42 diabetic patients were matched with 42 non-diabetic patients according to age, sex, year of starting treatment, and type of treatment (dialysis or transplantation). MAIN OUTCOME MEASURES: Sex, age, renal biopsy findings, blood pressure, history of diabetic treatment, and plasma creatinine concentration at the start of renal replacement treatment. History of renal replacement treatments, suitability for transplantation, history of transplantation, cumulative survival, and cause of death during follow up. Survival of technique, cumulative survival of the first peritoneal catheter and history of peritonitis in patients treated with continuous ambulatory peritoneal dialysis; source of graft, histocompatibility antigens, duration of associated stay in hospital, and graft survival in patients receiving renal or pancreatic transplant. RESULTS: 1259 Patients with chronic renal failure were accepted for renal replacement treatment in Newcastle upon Tyne, of whom 65 (5%) had diabetes. The first was accepted in 1974, and between 1974 and 1980 another 15 were treated (mean age 42 years; 4% of new patients). From 1981 to 1987, 49 diabetic patients (mean age 44; 9% of new patients) were treated. Fifty patients (77%) had insulin dependent diabetes and the remaining 15 (23%) non-insulin dependent diabetes. On average, the patients were aged 25 (range 5-57) when diabetes was first diagnosed and 44 (range 24-70) at the start of renal replacement treatment. The mean age at the start of treatment was 40 for patients with non-insulin dependent diabetes and 58 for patients with non-insulin dependent diabetes. Transplantation was performed in 33 of the diabetic patients, whose mean age was lower than that of those who did not receive a transplant (41 v 48 respectively, p less than 0.05). Comparison between the 42 diabetic patients and matched controls showed that the overall survival at five years was 46% and 77% respectively. The three year survival of the diabetic patients who did not receive a transplant was poor (41% v 79% respectively). Of patients transplanted, survival at five years was 73% in the diabetic patients and 90% in the controls. However, there was no significant difference in the five year graft survival (64% v 46% respectively). CONCLUSIONS: Diabetes adversely affects morbidity and mortality in patients having renal replacement treatment, but renal transplantation seems to be the best option for treating diabetic patients with end stage renal failure. PMID- 2207427 TI - Outcome of renal replacement treatment in patients with diabetes mellitus. AB - OBJECTIVE: To compare the outcome of renal replacement treatment in patients with diabetes mellitus and in non-diabetic patients with end stage renal failure. DESIGN: Retrospective comparison of cases and matched controls. SETTING: Renal unit, Western Infirmary, Glasgow, providing both dialysis and renal transplantation. PATIENTS: 82 Diabetic patients starting renal replacement treatment between 1979 and 1988, compared with 82 matched non-diabetic controls with renal failure and 39 different matched controls undergoing renal transplantation. MAIN OUTCOME MEASURES: Patient characteristics, history of smoking, prevalence of left ventricular hypertrophy and myocardial ischaemia at start of renal replacement treatment; survival of patients with renal replacement treatment and of patients and allografts with renal transplantation. RESULTS: The overall survival of the diabetic patients during the treatment was 83%, 59%, and 50% at one, three, and five years. Survival was significantly poorer in the diabetic patients than the controls (p less than 0.001). Particularly adverse features for outcome at the start of treatment were increasing age (p less than 0.01) and current cigarette smoking (relative risk (95% confidence interval) 2.28 (0.93 to 4.84), p less than 0.05). Deaths were mainly from cardiac and vascular causes. The incidence of peritonitis in patients on continuous ambulatory peritoneal dialysis was the same in diabetic patients and controls (49% in each group remained free of peritonitis after one year), and the survival of renal allografts was not significantly worse in diabetic patients (p less than 0.5). CONCLUSIONS: Renal replacement treatment may give good results in diabetic patients, although the outlook remains less favourable than for non-diabetic patients because of coexistent, progressive vascular disease, which is more severe in older patients. PMID- 2207429 TI - Vaccinations and professional confusion. PMID- 2207428 TI - ABC of major trauma. Trauma of the lower urinary tract. PMID- 2207430 TI - Fetal and placental size and risk of hypertension in adult life. PMID- 2207431 TI - Warning leak in subarachnoid haemorrhage. PMID- 2207432 TI - Treatment for lichen sclerosus. PMID- 2207433 TI - Caseload or workload? PMID- 2207434 TI - Cell implantation in Parkinson's disease. PMID- 2207436 TI - Perioperative deaths among children. PMID- 2207435 TI - Psychiatric aspects of urinary incontinence. PMID- 2207437 TI - Liver function tests. PMID- 2207438 TI - Mortality in patients with bleeding peptic ulcer. PMID- 2207439 TI - Partial purification and properties of rat urine arylamidases. AB - 1. Arylamidases were isolated from rat urine using L-aminoacyl-2-naphthylamides and L-Leu-p-nitroanilide as substrates to monitor the purification. 2. Ion exchange chromatography separated three peaks of activity (A, B and C). After gel filtration chromatography, the second and third peaks (B and C) were further purified to provide B1 and C1. Each behaved like a single active protein band on 7.5% polyacrylamide gel electrophoresis without SDS. The molecular weights of fractions B1 and C1 determined by SDS-PAGE were 440 and 270 kDa, respectively. 3. The pH optimum for arylamidase activity was 7.5 for both forms on all substrates tested. The maximum value for the Vmax/Km ratio was obtained using L-Leu-2 naphthylamide as substrate for both forms. 4. The arylamidase activity of B1 and C1 was not affected by the presence of chloride ions and was increased in the presence of CaCl2 and MnCl2 only when L-Glu-2-naphthylamide was used as substrate. EDTA (3.3-33.0 microM) and o-phenanthroline (0.1-1.0 mM) but not -SH (0.08-0.67 mM) or -S-S-(0.42-3.3 mM) group reagents inhibited the arylamidase activity. Hydrolysis of L-Leu-2-naphthylamide by fractions B1 and C1 was competitively inhibited by leucine (0.14-0.56 mM), indomethacin and puromycin (67 267 microM) and bestatin (8.3-33.3 microM). For each inhibitor, the Ki values were similar in the two fractions: 100 microM for L-leucine, 10 microM for indomethacin and puromycin and 1.0 microM for bestatin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2207440 TI - Biochemical and immunochemical identification of the fetal polypeptides of human amniotic fluid during the second trimester of pregnancy. AB - 1. Human amniotic fluid contains a complex mixture of proteins, of which only the minority are of fetal origin. We have identified the fetal polypeptides of second trimester amniotic fluid samples by two different methods. 2. The first method was the side by side comparison of silver-stained two-dimensional polyacrylamide gels of amniotic fluid polypeptides with pregnant female plasma polypeptides, after passage of both through a Blue Sepharose affinity column to remove albumin. The second method was the identification of the fetal polypeptides in two dimensional Western blots with an antiserum made specific for fetal proteins. 3. Using these techniques we have identified 13 major fetal polypeptide fractions with apparent molecular weights of 220, 200, 82, 70, 59, 52, 50, 36, 30, 25, 20, 18 and 11 kDa. Five of these polypeptides, with molecular weights of 82, 59, 50, 20 and 18 kDa, have not previously identified. The identification of these fetal components provides a reference base for molecular studies of normal and pathological fetal development. PMID- 2207441 TI - Lack of association between thyroid function and mitral valve prolapse in Graves' disease. AB - 1. To determine whether the association between mitral valve prolapse and Graves' disease is related to thyroid function, three groups of individuals were studied: 16 patients with Graves' disease and hyperthyroidism (hyperthyroid: T4 greater than 11.5 micrograms/100 ml), 16 patients with Graves' disease without hyperthyroidism (euthyroid: T4 less than 11.5 micrograms/100 ml), and 40 healthy individuals. The three groups were similar in age, sex distribution, and anthropometrical characteristics. 2. All patients were evaluated clinically and by M-mode and two-dimensional echocardiography to determine the presence of mitral valve prolapse. 3. The frequency of mitral valve prolapse was similar in the hyperthyroid (31%) and euthyroid patients (25%), but was higher than in the normal individuals (5%). The frequency of systolic murmur was higher in the hyperthyroid patients (75%) than the euthyroid patients (19%) or the normal subjects (0%); however, the presence of a murmur was not associated with mitral valve prolapse. Hyperthyroid (13%) and euthyroid (13%) patients had a higher frequency of clicks than the normal individuals (0%), and the presence of click was associated with mitral valve prolapse. 4. Although patients with Graves' disease have a higher frequency of mitral valve prolapse, this is not associated with thyroid function. The presence of a click but not the presence of a systolic murmur may be a clinical indicator of mitral valve prolapse in Graves' disease. PMID- 2207442 TI - Two-site immunoassays for the measurement of serum laminin: correlation with breast cancer staging and presence of auto-antibodies. AB - 1. Binding to and destruction of basement membrane (BM) are necessary steps for cancer cells to extravasate and metastasize. Serum levels of released BM components may correlate with the staging of human cancers or with inflammatory disorders. Furthermore, released material may also induce autoantibodies. Since laminin, an 800-kDa glycoprotein, is present in the extracellular matrix, serum laminin levels may be markers of BM injury. 2. A two-site enzyme immunoassay and a radioimmunoassay were developed to test sera from patients with breast cancer or systemic lupus erythematosus (SLE). 3. A significant difference in laminin concentrations was demonstrated between early (T0-T2) and advanced (T3-T4) tumors (P = 0.001). However, specimens from SLE patients did not differ in laminin concentration from normal individuals and no correlation was observed between laminin levels and anti-laminin auto-antibody titers. 4. These results suggest that serum laminin levels are useful markers of BM damage and could be of prognostic value in cancer. PMID- 2207443 TI - Chronically inflamed tissue activates plasma mediators of vascular permeability. AB - 1. After inflammation was induced in the foot-pad of rats with nistatin or BCG, injection of "non-activated" homologous plasma at the inflamed site caused a significant increase in the vascular permeability of the lesions (Evans blue test), which was more intense in older lesions, increasing from 7.83 +/- 1.11 to 8.70 +/- 1.18 (nistatin, 4 and 21 days) and 7.30 +/- 0.66 to 7.54 +/- 0.80 (BCG, 4 and 21 days). 2. Steroidal (acetyltriamcinolone, 2 mg/kg) and non-steroidal (indomethacin, 25 mg/kg) [corrected] anti-inflammatory drugs markedly decreased this effect on 14-day old lesions induced by nistatin plus "non-activated" plasma (2.37 +/- 0.10 for acetyltriamcinolone treatment vs 8.15 +/- 1.22 for untreated animals; 3.34 +/- 0.41 for indomethacin treatment vs 8.15 +/- 1.22 for untreated animals) and BCG plus "non-activated" plasma (1.67 +/- 0.11 for acetyltriamcinolone treatment vs 10.27 +/- 0.52 for untreated animals; 5.87 +/- 0.35 for indomethacin treatment vs 9.14 +/- 0.23 for untreated animals). 3. These data suggest that an increase in exudation in chronic lesions might result in "reactivation" of the process as observed clinically, for example, in rheumatoid arthritis in man. PMID- 2207444 TI - Hyperosmotic sodium chloride partially blocks the effects induced by Bothrops jararaca venom on vascular permeability and hemorrhage in the rat. AB - The effect of the administration of hyperosmotic NaCl (2 ml, 7.8% NaCl, iv) on hemorrhage and vascular permeability changes induced by Bothrops jararaca venom in rats was determined 30 min after venom injection. This treatment given immediately after subcutaneous venom injection significantly reduced the hemorrhagic manifestations by 33%. The increase in vascular permeability was significantly reduced when the animals were pretreated with hyperosmotic saline or mannitol 15 min before receiving the venom (26% and 20%, respectively). However, when animals were treated immediately after venom injection, only the hyperosmotic NaCl solution significantly reduced vascular permeability (32%). Isotonic NaCl treatment had no effect on hemorrhagic lesions or vascular permeability. PMID- 2207445 TI - Isolation of a lectin from the marine sponge Desmapsama anchorata by affinity chromatography on raffinose-sepharose 6B. AB - A mitogenic lectin for human lymphocytes is present in the marine sponge Desmapsama anchorata. The protein hemagglutinates red blood cells irrespective of ABO group antigens. We now report the isolation of this lectin, by affinity chromatography on a column of raffinose conjugated to epoxy-activated Sepharose 6B, in 8.3% yield and with a purification index of 27 based on hemagglutinating activity. The isolated lectin is a glycoprotein with two subunits with molecular weights of about 18 and 36 kDa which display carbohydrate combining sites of similar specificities and can be associated in different forms. PMID- 2207446 TI - Depressed respiratory sinus arrhythmia: additional evidence for impairment of vagal activity in human hyperthyroidism. AB - The efferent activity of the parasympathetic component of the autonomic nervous system was evaluated by measuring the magnitude of the respiratory sinus arrhythmia in 3 female patients with hyperthyroidism (Basedow-Graves' disease) before and after treatment. The heart rate variations induced by the test increased in all patients after treatment of thyrotoxicosis (from 15 +/- 2.9 to 28.3 +/- 6.6 beats/min; mean +/- SEM) with propylthiouracil (600 mg/day). This result confirms our previous observations indicating an important and reversible impairment of the efferent vagal activity in human hyperthyroidism. PMID- 2207448 TI - Relationship between differing volumes of bone marrow aspirates and their cellular composition. AB - We compared the cellular composition of the first 1.0 ml volume bone marrow aspirate with that of an aliquot from the total bone marrow harvest at the end of the procedure in 17 healthy bone marrow donors. Each sample was assayed for its content of red blood cells, nucleated cells, CD2+, CD4+, CD8+, CD19+, HLA-DR+, CD56+, CD13+, CD33+, CD34+ and KiM8+ cells and CFU-GM. On the basis of data obtained, we estimated that the first 1.0 ml samples had 8.0 +/- 5.2% (SD) and the transplant samples 20.8 +/- 8.5% contamination with nucleated blood cells. The calculation revealed that both types of bone marrow samples had 100% volume contamination with peripheral blood, i.e. that bone marrow cells were aspirated within blood fluid volume. Nucleated cell concentration was 3-fold, and CFU-GM concentration 10-fold lower in the transplant than in the first-puncture 1.0 ml bone marrow samples. Various marker-positive cells appeared in transplant samples in concentrations that depended on their abundance in the first-puncture 1.0 ml and blood samples. Taken together, our data suggest that bone marrow harvesting would be substantially improved if individual aspirates were small in volume and taken from bone puncture sites as distant as possible. PMID- 2207447 TI - Desipramine blocks stress-induced prolactin release in rats: role of central beta 2 adrenoceptors. AB - 1. The present study was designed to examine the relationship between beta adrenoceptors and the enhanced, sustained prolactin secretion induced by immobilization stress in rats. 2. Chronic administration of desipramine (15 mg kg 1 day-1, intraperitoneally) for 7 days, a procedure that desensitizes central beta-adrenoceptors, partially inhibits stress-induced prolactin release. 3. Intracerebroventricular administration of the beta-2 adrenoceptor agonist salbutamol (1 microgram/rat) to rats pretreated with desipramine for 7 days, 15 min before immobilization, significantly relieved the inhibition by desipramine 5 and 10 min after the initiation of stress but the effect was not demonstrable after 20 and 40 min. 4. We conclude that beta-2 adrenoceptors play a role in the control of prolactin release in response to stress. PMID- 2207450 TI - Combination of cyclosporin and methotrexate for prophylaxis of acute graft-versus host disease after allogeneic bone marrow transplantation for leukemia. AB - From May 1985 to July 1989, 76 patients with leukemia (30 acute myelogenous leukemia, 24 acute lymphoblastic leukemia and 22 chronic myeloid leukemia) were randomized to receive either cyclosporin (CSP) alone (n = 39) or CSP combined with methotrexate (CSP + MTX, n = 37) for graft-versus-host disease (GVHD) prophylaxis. Patients were conditioned with total body radiation and cyclophosphamide followed by bone marrow infusion from an HLA-identical sibling. Engraftment of the transplanted bone marrow was similar in both groups. The incidence of moderate to severe acute GVHD was significantly higher in the CSP group compared with the CSP + MTX group (20 (51%) versus 9 (25%), chi 2 = 4.76, p less than 0.02). There was no significant difference in the incidence of chronic GVHD. Survival was significantly better for the CSP + MTX group (63 +/- 16%) compared to CSP alone (42 +/- 18%). Leukemia-free survival tended to be better for the CSP + MTX group (55 +/- 17% versus 32 +/- 16%). PMID- 2207449 TI - Markedly increased serum erythropoietin levels following conditioning for allogeneic bone marrow transplantation. AB - Serum erythropoietin (EPO) levels were measured by radioimmunoassay in 36 patients undergoing allogeneic bone marrow transplantation (BMT). Serum EPO levels before conditioning treatment for BMT were generally higher than the levels obtained from healthy controls (49 +/- 17 (SEM) and 17 +/- 0.6, respectively). One day prior to BMT, after conditioning by chemotherapy with or without total body irradiation, the mean EPO level was markedly elevated (218 +/- 23 U/l, p less than 0.001) and reached to its highest level at 1 week post-BMT (269 +/- 40 U/l). Although, the EPO levels were significantly lower at 1 month (98 +/- 24 U/l, p less than 0.001), they were still elevated up to 3 months post BMT, after which they gradually normalized. Patients given methotrexate and cyclosporine for prophylaxis against graft-versus-host disease (GVHD) had significantly lower EPO levels during the first 3 months post-BMT than patients transplanted with T cell-depleted marrow (p less than 0.05). Patients with post transplant nephrotoxicity had lower, though not statistically significant, EPO levels than patients with normal renal function (p = 0.07). Acute GVHD and number of blood transfusions had no influence on serum EPO levels after BMT. PMID- 2207451 TI - Cortical blindness: a rare complication of cyclosporine therapy. AB - We report a bone marrow transplant patient who developed a reversible episode of cortical blindness, a rare complication of cyclosporine therapy. We review previously reported cases and the mechanisms involved in this complication. PMID- 2207452 TI - Diminished tear production in BMT recipients not receiving radiation. PMID- 2207453 TI - Pseudotumor cerebri after ABMT. PMID- 2207454 TI - Late complications after allogeneic bone marrow transplantation for leukaemia. AB - Late effects of bone marrow transplantation are of clinical concern as more patients survive the early phase after transplantation and remain free of their original disease. Late effects express themselves as structural or functional impairment of organs or tissues or as neoplastic growth secondary to the primary treatment. Non-neoplastic late effects affect growth and development of children, endocrine and reproductive function, and the function of eyes, lungs, kidneys and other organs. Secondary neoplasms comprise malignant lymphoma and leukaemia, many of them in donor cells, that occur early after transplantation. The incidence of solid tumours is increased years after transplantation. At present the risk of secondary neoplasms after transplantation appears not to be different from that of intensive chemoradiotherapy without transplantation. In contrast to conventional chemoradiotherapy secondary malignancies of the host's haemopoiesis are rare due to the myeloablative conditioning. The incidence of solid tumours may increase as more patients survive more than a decade after transplantation. PMID- 2207455 TI - What is the role of recombinant colony stimulating factors in bone marrow transplantation? AB - Colony stimulating factors (CSFs) regulate production of myeloid cells. Use of CSFs post bone marrow transplant accelerates granulocyte recovery by shortening the interval of relative but not absolute granulocytopenia. Data from non randomized trials suggest that CSFs decrease documented infections by about one third; there is no apparent increase in survival. Adverse effects of CSFs are modest; there are no indications of increased graft failure, graft-versus-host disease or cancer recurrence after their use. Future studies of CSFs should be in the context of randomized trials where their therapeutic efficacy is best evaluated. CSFs may also be useful in other transplant settings such as treating graft failure or increasing the efficiency of harvesting myeloid progenitor cells from the blood for subsequent transplantation. Controlled trials are needed to evaluate these uses. Future directions will probably include combinations of CSFs and, possibly, in vitro treatment of the graft. PMID- 2207456 TI - Impaired glucose tolerance after autologous bone marrow transplantation. AB - In this study we investigated glucose tolerance in relation to autologous bone marrow transplantation (ABMT). In 13 adult patients with acute myeloblastic (AML) or lymphoblastic (ALL) leukaemia in complete remission (CR), intravenous glucose tolerance test (IVGTT) was performed 1 month before and 6 months after ABMT. Patients with AML in CR received, as myeloablative therapy, cyclophosphamide combined with busulphan or total body irradiation (TBI). ALL patients received total body irradiation in combination with vincristine, daunorubicin, Ara-C, cyclophosphamide and prednisone. Before ABMT all patients, in spite of the intensive chemotherapy given for remission induction and consolidation, had a normal glucose tolerance. However, 6 months after the transplantation the k-value (rate of glucose elimination) for this group of patients had decreased (p less than 0.01). The trend towards impaired glucose tolerance was correlated with lower peak insulin values during IVGTT (p less than 0.05). Thus, the myeloablative therapy in connection with ABMT caused an impairment of pancreatic beta-cell function. No patient has hitherto developed clinical diabetes mellitus. PMID- 2207457 TI - Autoantibodies in chronic GVHD: high prevalence of antinucleolar antibodies. AB - Sera from 32 bone marrow allograft recipients were screened for the presence of autoantibodies 4-61 months post-graft. Sera from 12 of 19 patients with extensive chronic graft-versus-host disease (c-GVHD) stained the nucleolar region strongly in immunofluorescence, indicating the presence of specific antinucleolar antibodies. In contrast, none of three patients with limited and none of 10 patients without c-GVHD had antinucleolar antibodies. Antibodies reacting with nuclear constituents other than nucleoli were found in five of the 12 antinucleolar positive patients. The appearance of antinucleolar antibodies coincided with early clinical symptoms of c-GVHD. We conclude that the appearance of antinucleolar antibodies after bone marrow transplantation is specific for patients with extensive c-GVHD. Furthermore, the development of extensive c-GVHD is paralleled by the emergence of these antinucleolar antibodies. PMID- 2207458 TI - Soluble interleukin 2 receptors in patients after bone marrow transplantation. AB - An enzyme-linked immunosorbent assay was used to quantify soluble interleukin 2 receptor (IL2R) in the serum of 25 patients prior to allogeneic or autologous bone marrow transplantation and in the early post-transplantation period. A significant correlation between IL2R and the occurrence of fever and/or graft versus-host disease (GVHD) could be shown. Patients with moderate to severe GVHD (grade II-IV) had significantly higher IL2R levels (median 480 U/ml) than patients without or with acute GVHD grade I (median 139 U/ml). In patients without or with acute GVHD grade I, significant differences in the maximum IL2R levels depended on the duration of fever greater than or equal to 38 degrees C. Evaluation of the peak IL2R levels in patients with fever lasting longer than 6 days led to a median of 260 U/ml and in patients with fever lasting less than 6 days to a median of 118 U/ml. In patients without or with acute GVHD grade I, who developed fever lasting longer than 6 days, IL2R levels started to rise with the onset of fever, reached peak values during temperature maximum and declined parallel with temperature normalization. In patients without or with acute GVHD grade I who developed fever lasting for only 6 days or less IL2R levels remained within the normal range. In patients with acute GVHD grade II-IV, IL2R levels began to rise with the onset of fever, and then continued to rise despite temperature normalization. The peak levels were reached in the early period of acute GVHD. Our observations in BMT patients show that severe infections and acute GVHD are associated with a stimulation of the immune system leading to elevated IL2R serum levels. PMID- 2207459 TI - [Academic eulogy of doctor Ludo van Bogaert, titular member and former president]. PMID- 2207461 TI - [Lyme disease: clinical and sero-epidemiological study of Borrelia burgdorferi infections in Belgium]. AB - Lyme disease is a multi-systemic infection caused by the spirochaete Borrelia burgdorferi: this bacterium, discovered in 1982 in the United States, is mainly transmitted by a tick bite, Ixodes ricinus in Europe. In Belgium, a first seroepidemiological study of 3 years has revealed 190 patients and the whole spectrum of clinical pictures was observed, including the early stage of this infection in the skin (erythema chronicum migrans), neurological involvement and arthritis. The Lyme borreliosis is endemic in our country: the incidence ranges from low near the coast to high in the south-eastern part of Belgium. PMID- 2207460 TI - [Antiseptic properties of saliva and metabolism of activated oxygen in neutrophils: comparison of the 2 enzymatic bactericidal systems and of their behavior in an acid environment]. AB - Growth control of anaerobes in the oral cavity, is secured--among other means- by: 1) phagocytosis of opsonized bacteria; 2) synthesis of hypothiocyanite by the salivary peroxidase system. The former may be inhibited by bacterial acid byproducts. As for the salivary hypothiocyanite, it proved itself able of hindering in vitro the growth of bacterial strains known as customary periodontal pathogens. Its possible effectiveness in vivo remains however hypothetical in the case of deep gingival pockets according to the poor diffusion there of salivary components. PMID- 2207462 TI - [Early stages and development of chronic obstructive pneumopathy]. AB - Chronic obstructive lung disease (COLD) is an important cause of mortality and disability. In a cross-over study, followed by a longitudinal one, of a homogeneous group of blue collar steel workers, we have found that the slope of the N2 alveolar plateau was the most frequently impaired test, in the absence of any respiratory symptom. However, its predictive power was low enough to preclude its use for early detection of COLD. We have now a better understanding of the issues of early detection of COLD, the risk factors involved as well as of the therapeutic intervention to improve its prognosis. PMID- 2207463 TI - [Current aspects of AIDS]. AB - HIV epidemic is still expanding all over the world. Heterosexual transmission into the general population is of particular concern mostly in Africa and Western countries. So far, pathogenesis of the syndrome is best explained by the likely role of co-factors that interfere with the latency phase of the virus. In this setting early treatment by specific antiviral therapy such as zidovudine, will probably slow down the evolution of HIV infection. PMID- 2207465 TI - Sibling incest: a consequence of individual and family dysfunction. AB - Sibling incest has seldom been researched and thus remains poorly understood. The authors review a case and discuss it in the context of the recent literature on incest. The case report they present demonstrates the complexity of individual and family dynamics leading to incest and illustrates the need for caution in making generalizations about incestuous families. The authors recommend that evaluators and treaters of incestuous families pay close attention to the specific dynamics of any given case and avoid assuming that common scenarios or traits of participants alone can adequately explain the incest. PMID- 2207464 TI - Incest perpetrators in group therapy: a psychodynamic perspective. AB - Patients who have been sexually abusive toward children in their family often have guarded prognoses. However, the legal system's promotion and support of treatment elicits cautious optimism; even limited progress can make a significant difference in the lives of these persons and their families. The authors report on their work with incest perpetrators in a psychoanalytically oriented psychotherapy group with 20 incest offenders (selected after evaluation of 50), describing major obstacles (i.e., patients' lack of motivation and countertransference) and frequent clinical issues (i.e., perversion, psychopathic tendencies, low self-esteem, and substance abuse). PMID- 2207467 TI - Developing an alliance with schizophrenic patients in day hospital treatment. AB - For schizophrenic patients, denial of illness and resistance to treatment are pervasive during the subacute phase of the illness. The authors conceptualize these phenomena from a developmental perspective, with particular emphasis on self-reintegration. Theoretical concepts are discussed and guidelines for developing a treatment alliance are described. Clinical examples drawn from experience with schizophrenic patients in a day hospital setting are provided. PMID- 2207466 TI - Psychoanalytic perspectives on the use of medication for mental illness. AB - The author examines the use of psychoactive medication from the psychoanalytic perspective. He notes that medication has psychological meaning and acquires additional mental representation, and that pharmacotherapy interventions may obscure the differentiation between direct effects of medication on patients and neurotic conflicts in patients. He discusses specific factors involved in the decision to prescribe medication, including the patient's and the clinician's own readiness to use medication, medical countertransference, and common pharmacotherapy interventions (suggestion, manipulation, and inexact interpretation). A case report illustrates issues involved in combined psychoanalytic and neurobiological treatment. PMID- 2207468 TI - Dante, psychoanalysis, and the (erotic) meaning of meaning. AB - The author observes a resemblance between (1) the "polysemous" technique of imputing meaning to reality practiced in medieval biblical studies and in Dante's writing and (2) the technique of interpretation in contemporary psychoanalysis. She explores the roots of this resemblance in the development of intellectual history and provides examples of polysemous meanings in Dante's Divine Comedy, which is in part an autobiographical journey of self-reflection and self realization (like psychoanalysis). She then suggests some implications of this resemblance for contemporary psychiatry. PMID- 2207469 TI - Scales for assessing family intervention during psychiatric hospitalization. AB - Because ample evidence from both clinical and research realms has demonstrated that family intervention can be crucial for the process and outcome of psychiatric hospital treatment, greater attention should be given to assessing the extent and content of such interventions. The authors present their rating system for assessing the focus of family interventions during psychiatric hospitalization; they also provide results of a study of the interrater reliability of the scales and a factor analysis of the scales. These Family Intervention Scales are designed for application in hospitals that vary widely in structure, setting, staffing patterns, and program emphasis. The factor analysis yields four factors that make good clinical and conceptual sense: Information Education, Family System Approach, Family Therapeutic Alliance, and Spouse Involvement. PMID- 2207470 TI - Suicidal patients' psychological attacks on the therapist. AB - In therapy, suicidal borderline patients often use the therapist as a "selfobject," an object that regulates the patient's narcissistic equilibrium. To demonstrate this concept, the author presents the case history of a young woman who created a "selfobject transference" by means of attacks on the therapist similar to those she herself had experienced in childhood. Her massive, hidden attacks were also troublesome to the therapists' own feeling of self-worth. PMID- 2207471 TI - The interviewer's "presenting problems" in the initial interview. AB - Complex countertransference responses that contribute to the interviewer's presenting problems in the initial interview with a patient are related to: the clinician's preinterview fantasies, the interviewee's empirical reality, and the patient as experienced creatively. Presenting problems may be an unavoidable component of clinical contact, but when the interviewer responds to them with psychological-mindedness, they can contribute to realistic assessment and positive case disposition. PMID- 2207472 TI - Cognitive-behavioral approaches to treating borderline and self-mutilating patients. AB - The cases of three self-injurious patients suffering with borderline personality disorder are briefly presented. From this clinical base, the consultant describes a cognitive-behavioral psychotherapeutic model and how it might be applied to the treatment of these and similar patients. A dialectical behavioral approach is used to describe three major dichotomies and their application. The consultant also illustrates how cognitive-behavioral therapy may be integrated with more dynamic-analytic approaches, and proposes a strategy and methodology that establish and reinforce the treatment alliance in developing a treatment plan. PMID- 2207473 TI - Transactions of the Topeka Psychoanalytic Society. PMID- 2207474 TI - Systemic inflammatory disease and the eye. AB - Systemic inflammatory diseases are a spectrum of immunologically mediated disorders that present with multisystem symptoms and signs. Ophthalmological examination often provides important clinical clues to the nature of the underlying disorder and characteristic ocular patterns may be identified that aid diagnosis. This article summarizes the ocular manifestations of systemic inflammatory disease and suggests a rational approach to diagnosis based on the type of ocular vessel predominantly involved in the inflammatory process. PMID- 2207475 TI - Postsurgical care of elderly women with fractures of the proximal femur. AB - The outcome for elderly women suffering a fracture of the proximal femur remains poor. Attempts to improve care in the past have mainly focused on surgical and perioperative techniques. More recently evidence has become available showing the impact of postoperative and rehabilitative care in these frail elderly patients. This article highlights this evidence and provides practical guidelines for good clinical practice. PMID- 2207476 TI - Trauma scoring methods. AB - Trauma scoring methods are recommended for use in the management of trauma patients. Currently used methods are reviewed for their use in triage, the determination of injury severity and the assessment of prognosis and outcome in comparative evaluation of trauma care within or between institutions. PMID- 2207477 TI - Family therapy. AB - Everyone has heard about family therapy, but few outside the movement know what family therapists think or do. Is it a current vogue or a valid form of intervention? On what ideas is it based? Are there many forms or only one, and above all does it work? This article attempts to answer these questions. PMID- 2207478 TI - How to perform a diagnostic peritoneal lavage. AB - Peritoneal lavage can be a very helpful investigation in the initial management of trauma patients. The technique demands some basic surgical skills but has been shown to be relatively safe and accurate when performed by appropriately trained junior doctors. PMID- 2207479 TI - An unusual hysteroscopic finding in association with primary carcinoma of the fallopian tube. PMID- 2207480 TI - The radiological features of bone tumours. AB - Radiological investigation is an invaluable method of demonstrating the presence, location, and size of a bone tumour but is often of less value in establishing its nature. Perhaps one should question the practice of attempting a histological diagnosis from a radiological investigation. PMID- 2207481 TI - FRCS. Case 2. A colonic polyp. PMID- 2207482 TI - Vagal reflexes and anaesthesia. PMID- 2207483 TI - Keeping perspectives in health care. PMID- 2207484 TI - Accreditation of diagnostic laboratories. PMID- 2207485 TI - An alternative solution to an anaesthetic dilemma. PMID- 2207486 TI - Do consultants hold the key to an improved health service? PMID- 2207487 TI - Inefficiency of the NHS: the patient's responsibility. PMID- 2207488 TI - A dedicated helicopter-based ITU has all the advantages. PMID- 2207490 TI - Further comment on anticoagulants in cardiovascular disease. PMID- 2207489 TI - Analgesia during labour in drug addicts. PMID- 2207491 TI - Surgical alternatives to hysterectomy for intractable menorrhagia. AB - When conservative measures fail to control menorrhagia, most women have been offered hysterectomy. Endoscopic endometrial ablation presents a less radical alternative which appears to have significant advantages in patient acceptance and reduced hospital stay. The long-term outcome of these techniques remains uncertain. PMID- 2207492 TI - L-NG-nitro arginine inhibits non-adrenergic, non-cholinergic relaxations of guinea-pig isolated tracheal smooth muscle. AB - The effects of L-NG-nitro arginine (L-NOARG) on alpha-chymotrypsin-resistant, non adrenergic, non-cholinergic (NANC) relaxations of guinea-pig tracheal smooth muscle have been examined. L-NOARG (1-100 microM), but not D-NOARG (100 microM), inhibited the NANC relaxations in a concentration-related manner. The effects of L-NOARG were partially reversed by L-arginine but not D-arginine. L-NOARG was without effect on acetylcholine-induced contractile responses of the trachea or on relaxations produced by vasoactive intestinal peptide, sodium nitroprusside or isoprenaline. These results suggest that an endogenous nitrate may contribute to NANC relaxations of tracheal smooth muscle. PMID- 2207493 TI - Mediation of 5-hydroxytryptamine-induced tachycardia in the pig by the putative 5 HT4 receptor. AB - Intravenous bolus injections of 5-hydroxytryptamine (5-HT; 3, 10 and 30 micrograms kg-1), 5-methoxytryptamine (5-MeO-T; 3, 10 and 30 micrograms kg-1), renzapride (BRL 24924; 3, 10, 30 and 100 micrograms kg-1) and isoprenaline (0.03, 0.1 and 0.3 micrograms kg-1) to anaesthetized pigs increased heart rate by, respectively, 22 +/- 3, 44 +/- 3 and 65 +/- 4 beats min-1 (5-HT; n = 17); 12 +/- 1, 26 +/- 2 and 44 +/- 4 beats min-1 (5-MeO-T; n = 15), 5 +/- 2, 11 +/- 2, 18 +/- 4 and 37 +/- 5 beats min-1 (renzapride; n = 8) and 17 +/- 2, 46 +/- 3 and 75 +/- 3 beats min-1 (isoprenaline; n = 13). The responses to 5-HT, 5-MeO-T and renzapride were antagonized by ICS 205-930 (1 and 3 mg kg-1, i.v.), which did not modify the increases in heart rate by isoprenaline. Renzapride showed tachyphylaxis and attenuated the responses to 5-HT. These findings indicate that 5-HT elicits tachycardia in the pig by acting on a novel receptor, either similar or identical to the 5-HT4 receptor identified in mouse brain colliculi. PMID- 2207494 TI - GABA(B)-related activity involved in synaptic processing of somatosensory information in S1 cortex of the anaesthetized cat. AB - 1. The possible role of GABA(B) receptor mechanisms in information processing in primary somatosensory (S1) cortex was assessed by use of extracellular recording combined with microiontophoretic methods from 161 neurones in anaesthetized, paralysed cats. 2. Baclofen-induced suppressions of cell responses were reversible and stereoselective, the (+)-isomer being inactive and the (-)-isomer having two to three times the apparent potency of gamma-aminobutyric acid (GABA). The responses measured were threshold to natural stimulation of receptive fields (RFs), responsiveness to thalamic electrical stimulation, change in RF size and magnitude of firing elicited by iontophoretic glutamate. 3. The action of GABA always was mimicked by muscimol or 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) but not always by (-)-baclofen; in certain cases (-)-baclofen enhanced neuronal responses while the opposite occurred with GABA or with the other GABA(A) agonists. The elevation of response thresholds by (-)-baclofen was relatively stronger in peripheral than in central subregions of cutaneous RFs, by contrast with the action of muscimol which was relatively non-selective as to the area in which it was effective. 4. Glutamate-induced and thalamically-evoked cortical responses as well as spontaneous activity were differentially sensitive to the suppressant effects of muscimol and (-)-baclofen. 5. Bicuculline methiodide reversibly blocked THIP- and muscimol-induced suppressions of tactile- (air puffer)-induced S1 responses but spared those produced by (-)-baclofen. Phaclofen and delta-amino-n-valeric acid were essentially inactive as blockers of (-)-baclofen-induced effects and in fact often acted as (-)-baclofen-like agonists, phaclofen being considerably weaker than delta-amino-n-valeric acid in this respect. 6. The range of suppressant effects produced by GABA as well as by muscimol and THIP, considered in conjunction with the actions of bicuculline methiodide, suggest that the effects observed by ejected GABA are likely to be due principally to GABA(A) processes, those mediated by GABA(B) receptors largely being masked. However, GABA(B) mechanisms are extant and do appear to be active, probably presynaptically and probably at sites distal to the soma. PMID- 2207495 TI - Lithium amplifies inhibitions of inositol phospholipid hydrolysis in mammalian brain slices. AB - 1. We have examined the effects of lithium chloride (LiCl) on inhibitions of inositol phospholipid hydrolysis in guinea-pig and rat brain slices by assessing the accumulation of [3H]-inositol phosphates ([3H]-InsP), in vitro. 2. In guinea pig and rat cerebral cortex slices the accumulation of total [3H]-inositol phosphates due to the cholinoceptor agonist carbachol was inhibited by the excitatory amino acid L-glutamate, but only when LiCl was present. 3. The effects of LiCl were time and concentration-dependent. Significant inhibitions of the carbachol response by glutamate (in the presence of LiCl) being evident only after 20-30 min of stimulation at LiCl concentrations above 1.2 mM. 4. N-methyl-D aspartate (NMDA), in the absence of LiCl, enhanced the response to carbachol at low concentrations of the amino acid and inhibited the response at higher concentrations. In the presence of 5 mM LiCl, only the inhibitory phase was observed. 5. In rat cerebral cortex slices, aluminium fluoride inhibited [3H] InsP accumulation in the presence of carbachol, noradrenaline and a depolarising concentration of KCl and these inhibitions were more marked when LiCl was present. The response to histamine was unaffected. 6. The data presented provide evidence that LiCl amplifies inhibitions of inositol phospholipid hydrolysis due to receptor and non-receptor mediated stimuli, although the mechanism underlying the effect is, as yet, obscure. PMID- 2207497 TI - Evidence that central 5-HT1A-receptors play a role in the von Bezold-Jarisch reflex in the rat. AB - 1. The effects of intracisternal (i.c.) application of putative 5 hydroxytryptamine (5-HT)1A antagonists on the reflex bradycardia evoked by injection of phenylbiguanide (i.v.) were investigated in anaesthetized, atenolol pretreated rats. 2. Intracisternal application of spiperone (100 micrograms kg-1) reversibly attenuated the reflex bradycardia whilst the same dose given i.v. had no effect. The bradycardia was also attenuated by i.c. methiothepin (200 micrograms kg-1), (+/-)-pindolol (100 micrograms kg-1) and buspirone (200 micrograms kg-1) but was not attenuated by antagonists selective for alpha 1 adrenoceptors (alfuzosin; 100 micrograms kg-1), 5-HT2-receptors (BW 501C67; 100 micrograms kg-1) or dopamine D2-receptors ((-)-sulpiride; 100 micrograms kg-1) given i.c. 3. It is concluded that the 5-HT1A-receptor antagonist action of intracisternally applied spiperone, methiothepin, (+/-)-pindolol and buspirone is responsible for the ability of these drugs to attenuate reversibly the excitation of cardiac vagal motoneurones caused by activation of the von Bezold-Jarisch reflex. PMID- 2207496 TI - The relationship between neutrophils and increased microvascular permeability in a model of myocardial ischaemia and reperfusion in the rabbit. AB - 1. 111In-labelled neutrophils and 125I-labelled albumin were used to measure neutrophil accumulation and microvascular plasma protein leakage in the ischaemic/reperfused myocardium of anaesthetized rabbits. 2. A period of 30 min coronary artery occlusion followed by 3 h reperfusion resulted in an increase in both 111In and 125I counts in the area at risk (AR) of the myocardium. 3. Pretreatment of 111In-neutrophils in vitro with monoclonal antibody 60.3 directed against the CD18 antigen on neutrophils, followed by intravenous administration, significantly suppressed their accumulation into the AR myocardium. 4. Depletion of circulating neutrophils by use of anti-neutrophil serum or mustine hydrochloride did not affect plasma protein leakage into the AR myocardium. 5. Administration of the platelet activating factor (PAF) antagonist WEB 2086 (10 mg kg-1, i.v.) had no effect on the accumulation of 111In-neutrophils or on plasma protein leakage in the AR myocardium. PMID- 2207499 TI - Effects of acute and chronic clozapine on dopamine release and metabolism in the striatum and nucleus accumbens of conscious rats. AB - 1. The effect of single and repeated (once daily for 23 days) oral doses of 20 and 60 mg kg-1 clozapine on dopamine release and metabolism were studied by intracerebral dialysis in the striatum and nucleus accumbens of conscious rats. 2. The basal output of dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum and nucleus accumbens of rats given clozapine 20 or 60 mg kg-1 chronically, measured one day after the last drug dose, was not significantly different from that of vehicle-treated animals. 3. Challenge doses of 20 or 60 mg kg-1 clozapine produced similar increases in dopamine levels in the striatum and nucleus accumbens of animals which had received vehicle or clozapine 20 or 60 mg kg-1 once daily for 23 days, except that 1 h after administration 60 mg kg-1 clozapine had a greater effect in the nucleus accumbens. 4. In animals treated chronically with clozapine 20 and 60 mg kg-1 or vehicle, DOPAC levels in the striatum and nucleus accumbens were increased to the same extent by challenge doses of clozapine (20 or 60 mg kg-1). In animals treated chronically with clozapine, a challenge dose of 60 mg kg-1 had significantly greater effect on HVA only in the nucleus accumbens. 5. When DOPAC and HVA were measured post mortem in the striatum and nucleus accumbens 2 h after various oral doses of clozapine, it was found that 10 mg kg-1 significantly increased dopamine metabolites only in the nucleus accumbens whereas 100 mg kg-1 had this effect in both regions. Clozapine, 30mgkg-' significantly raised DOPAC levels in both regions but HVA was elevated only in the nucleus accumbens. 6. There appeared to be no appreciable changes in dopamine release and metabolism nor any reduction in the effect of clozapine in the nucleus accumbens after chronic drug treatment. In fact the effect was greater in chronically treated rats, particularly in the nucleus accumbens of animals given 60mgkg' clozapine. 7. It was confirmed that measurement of dopamine metabolites in post mortem tissue provides no valuable information on changes in the availability of synaptic dopamine. PMID- 2207498 TI - The influence of the initial stretch and the agonist-induced tone on the effect of basal and stimulated release of EDRF. AB - 1. The effects of initial stretch and degree of agonist-induced tone on acetylcholine-induced relaxations were examined in rings of rat isolated aorta. The relaxation to acetylcholine was antagonized by atropine and almost completely abolished by haemoglobin. Relaxation to sodium nitroprusside was similar in rings with an intact or disrupted endothelium but that to isoprenaline was greater in intact preparations. 2. In preparations with either an intact or disrupted endothelium there was a similar length-dependent increase in the resting tension of the aortic rings. The size of the contractile response to phenylephrine (1 microM) was dependent on the initial length (and hence degree of stretch) of the preparation in both rubbed and unrubbed tissues. The absolute difference in contractile response between rubbed and unrubbed was greatest at 1.8 mm and less at the other lengths tested, including the optimum degree of stretch for contraction i.e. 2.4 mm. 3. The absolute acetylcholine-induced relaxation (only seen in rings with an intact endothelium) was dependent on the initial length (and hence degree of stretch) of the preparation and was maximum at 2.4 mm. The proportionate relaxation (i.e. expressed as a percentage of induced tone) was also length-dependent being optimal at 1.5 mm. 4. The sensitivity of the vessels to acetylcholine varied depending on the level of agonist-induced tone. When tone was low, acetylcholine sensitivity was high (at [NA] 0.03 microM: pIC50 = 7.36 +/ 0.07), when the concentration of noradrenaline was increased the tone increased and the acetylcholine sensitivity was low (at [NA] 0.3 microM: pIC50 = 6.57 +/- 0.07). 5. The absolute sensitivities and maximum relaxations induced by acetylcholine are discussed in relation to the initial degree of stretch (and hence length of the preparation) or the degree of agonist-induced tone. PMID- 2207500 TI - The effects of reported Ca2+ sensitisers on the rates of Ca2+ release from cardiac troponin C and the troponin-tropomyosin complex. AB - 1. The calcium sensitivity of force production of cardiac muscle fibres is altered by certain drugs. The sites of action of three such compounds (pimobendan, sulmazole, isomazole) within the myofibril have been investigated. Calmodulin antagonists, perhexilene and bepridil, which have been shown to alter the calcium dependence of myofibrillar ATPase activity and oxmetidine, an H2 receptor antagonist which binds to calmodulin, were also studied. 2. The rates of dissociation of calcium from both the regulatory and high affinity sites on bovine isolated cardiac troponin C (cTnC) were measured in a stopped-flow fluorimeter. The rates of dissociation were found to be 136.5 +/- 16 s-1 and 1.3 +/- 0.20 s-1 (mean +/- s.e.mean, n = 11 determinations; conditions: 100 mM KCl, 10 mM MOPS, 3 mM MgCl2, 0.1 mM dithriothreitol, pH 7.0, 15 degrees C). Sulmazole, isomazole and perhexiline (final concentration of 50 microM) had no effect on the rate of Ca2+ dissociation from the regulatory Ca2+ site, indicating that these compounds do not act on cTnC directly. 3. The rate of dissociation of Ca2+ from the regulatory site was slightly reduced (approximately 20%) by pimobendan (50 and 100 microM) and was somewhat increased by oxmetidine (28% at 100 microM). 4. Bepridil (25 microM) reduced the rate of dissociation by 50%, indicating a direct effect of bepridil on TnC. 5. Sulmazole, isomazole, perhexiline, pimobendan (50 microM) and bepridil (25 microM) were without effect on the rate of dissociation of Ca2+ from the high affinity Ca2+/Mg2+ sites. Oxmetidine caused 24% decrease in the rate of Ca2+ dissociation from these sites. 6. The rate of dissociation of Ca2+ from the regulatory site on the complex of troponin-tropomyosin (TnTm) was measured. Sulmazole and pimobendan (50 microM) were without effect on the rate of dissociation of Ca2+ from the regulatory site in the protein complex, and isomazole (50 microM) caused only a slight reduction (23%). Perhexiline (50 microM) or bepridil (10 microM) reduced the rate of Ca2 dissociation by about 50%. The rate of dissociation of Ca2+ from the high affinity Ca2 +/Mg2 + sites was not altered by sulmazole, isomazole, or pimobendan (50 microM), but was decreased - 35% by perhexiline (50 microM) or bepridil (10 microM). PMID- 2207501 TI - Effect of propentofylline (HWA 285) on extracellular purines and excitatory amino acids in CA1 of rat hippocampus during transient ischaemia. AB - 1. The adenosine uptake blocker propentofylline (HWA 285) has previously been shown to protect hippocampal CA1 pyramidal cells from ischaemia-induced delayed neuronal death. The influence of propentofylline, on the extracellular concentrations of purines, aspartate and glutamate in the CA1 of the rat hippocampus during transient forebrain ischaemia was investigated. 2. Twenty min of ischaemia was induced by four-vessel occlusion in Wistar rats, extracellular compounds were sampled by use of microdialysis and EEG was recorded by a tungsten electrode attached to the dialysis probe. 3. Propentofylline (10 mg kg-1 i.p.) did not influence the basal levels of any of the compounds in the hippocampal dialysates. 4. The EEG became isoelectric within 20 s after induction of ischaemia. 5. Extracellular adenosine, inosine, hypoxanthine, aspartate and glutamate increased several fold during ischaemia and remained elevated during early reflow. Within 2 h of reperfusion the concentration of all compounds was normalized. Xanthine increased upon reperfusion and remained elevated after 2 h. 6. Propentofylline (10 mg kg-1 i.p.) administered 15 min before ischaemia significantly enhanced the ischaemia-evoked increase of adenosine but attenuated the increases of the other purine catabolites and of glutamate. 7. In separate in vitro experiments, propentofylline did not inhibit adenosine deaminase activity. 8. The present data show that propentofylline enhances extracellular adenosine and lowers extracellular glutamate in vivo during ischaemia. These findings may be important in relation to the neuroprotective properties of propentofylline. PMID- 2207502 TI - Mechanisms for cardiac depression induced by phorbol myristate acetate in working rat hearts. AB - 1. The effects of the phorbol ester, phorbol myristate acetate (PMA) were examined on function and energy metabolism in the isolated working heart of the rat. 2. At a concentration of 10(-9) M PMA produced a rapid loss in cardiac function in terms of aortic flow rate (AFR) and coronary flow rates (CFR) whereas a similar concentration of 4 alpha-phorbol 12,13-didecanoate was ineffective. At a concentration of 10(-10) M, the PMA-induced depression was more gradual but nevertheless very pronounced with an almost total loss in AFR after 30 min perfusion. The reduction in CFR was more moderate than that observed with respect to AFR. 3. The protein kinase C (PKC) inhibitor (+/-)-1-O-hexadecyl-2-O acylglycerol significantly attenuated the loss in AFR and CFR following addition of PMA. 4. Two inhibitors of Na+/H+ exchange, amiloride and quinacrine, totally prevented the reduction in AFR. Although the PMA-induced depression in CFR was also attenuated by both amiloride and quinacrine, these effects were not significant, probably reflecting the less pronounced effect of PMA on this parameter. 5. Nifedipine, a dihydropyridine calcium channel blocker reduced PMA toxicity to a similar degree as Na+/N+ exchange inhibition whereas the calcium channel agonist Bay K 8644 was without effect. 6. Tissue content of energy metabolites including high energy phosphates, total adenine nucleotides or lactate were not significantly affected by PMA perfusion. 7. We conclude that PKC activation is necessary for phorbol ester-induced cardiac dysfunction. The consequence of PKC stimulation includes (1) Na+/H+ exchange activation and a subsequent elevation in intracellular calcium [Ca2+]i via Na+/Ca2+ exchange and (2) PKC-dependent phosphorylation of the calcium channel, both of which would produce toxicity by elevation of [Ca21]i. Pharmacological manipulation of any of these steps prevents PMA toxicity by virtue of a reduction in the accumulation of [Ca21]i. PMA effects or their prevention are unrelated to any changes in energy metabolism. PMID- 2207503 TI - The 'calcium sensitising' effects of ORG30029 in saponin- or Triton-skinned rat cardiac muscle. AB - 1. The effects of a range of concentrations of ORG30029 (1 microM to 1 mM) were investigated on fully (Triton-treated) or selectively (saponin-treated) 'skinned' ventricle trabeculae from rat. The Ca-sensitivity was increased by 100 microM and amounted to a mean reduction in the Ca2+ necessary for half-maximal activation (1/Kapp) of 0.174 +/- 0.053 (mean +/- s.e.mean) pCa units. ORG30029 (50 microM) gave a smaller mean shift of 0.05 +/- 0.016 pCa units. A slight shallowing of the relationship between -log[Ca2+] (pCa) and steady-state tension was also generally found (mean Hill exponent reduction 0.37 +/- 0.28 at 100 microM). 2. The Ca sensitizing action altered in a dose-dependent fashion. Judged by the ability to enhance force from an initial level of activation of 10-20% of maximum Ca activated force (Cmax), the first significant effects occurred near 10 microM and continued to increase at 1 mM. 3. A small (3.7 +/- 1.1%) but consistent increase in Cmax was produced by ORG30029 at 100 microM. Much larger increases were produced by the drug at higher concentrations (up to 20-50% at 1 mM). 4. The consequence of these changes is that at levels of activation likely to occur in the heart, the absolute increase in force by 100 microM ORG30029 was considerable: it amounted to a 150-200% increase at a [Ca2+] producing 20% at Cmax. At this drug concentration virtually all the effect was due to Ca sensitizing rather than increasing Cmax. 5. In the saponin-treated preparations, at concentrations up to 1 mM, ORG30029 did not release Ca from the sarcoplasmic reticulum, as indicated by the failure to evoke contracture under conditions where caffeine induced large responses. 6. At 100 microM, ORG30029 potentiated the transient, caffeine-induced contracture (saponin-treated preparation) to an extent consistent with the Ca-sensitizing effect seen under conditions of steady state tension development. PMID- 2207504 TI - Antiarrhythmic efficacy of labetalol as assessed by programmed electrical stimulation. AB - 1. The purpose of the present study was to investigate the haemodynamic, electrophysiological and antiarrhythmic effects of labetalol in the late reperfusion phase after myocardial infarction in conscious dogs. 2. Labetalol was administered in cumulative doses (0.5, 1 and 3 mg kg-1 90 min-1, i.v.). Compared to control the systolic blood pressure was significantly decreased 20 min after 0.5, 1 and 3 mg kg-1 and up to 30 min after 3 mg kg-1 labetalol. The diastolic blood pressure was significantly decreased 20 and 30 min after 0.5 and 3 mg kg-1 but was not significantly altered after 1 mg kg-1 labetalol. 3. Labetalol significantly increased the PQ, QRS, QT and QTc intervals, the 2:1 AV-conduction point, the ventricular effective refractory periods and the intraventricular conduction time from the apex of the right ventricle to the infarcted LAD-area. With the exception of the alterations in the PQ interval and 2:1 AV-conduction point the effects described above were dose-dependent. 4. Labetalol was active against arrhythmias induced by programmed electrical stimulation. This effect was already present after the lowest dose (0.5 mg kg-1). 5. The good antiarrhythmic activity of labetalol in this study can be explained by the adrenoceptor blocking properties and both the class I and III activity of this drug. Labetalol may be of potential benefit in controlling arrhythmias arising following myocardial infarction. PMID- 2207506 TI - The ontogeny of purinoceptors in rat urinary bladder and duodenum. AB - 1. The ontogeny of responses to purines and analogues of smooth muscle preparations was studied in rat duodenum and rat urinary bladder. 2. Responses to adenosine and to adenosine 5'-triphosphate (ATP) mediated by P1- and P2 purinoceptors respectively were present as early as postnatal day 2, the earliest day studied. 3. In rat bladder, adenosine was inhibitory and ATP and adenosine 5' (beta, gamma-methylene) triphosphonate (AMP-PCP) were excitatory, acting on the P2X subtype of P2-purinoceptors. Adenosine was more potent in the neonate than in the adult, while the potency of the nucleotides initially increased with age but then declined, being highest between postnatal days 10 and 25. 4. In rat duodenum also, adenosine was inhibitory, its potency being less than the adult before day 15. 5. ATP at low concentrations was inhibitory in rat duodenum at every age studied and its potency increased with age, but higher concentrations of ATP (3 microM and above) were excitatory until day 15. Both relaxations and contractions were mediated by the P2Y subtype of P2-purinoceptors. These ATP-induced contractions were not inhibited by indomethacin (25 microM) or by tetrodotoxin (1 microM) and are therefore not due to prostaglandin synthesis or to ATP-induced release of transmitter substances from nerves. 6. These results show that responses to adenosine and to adenine nucleotides are present from birth and vary with age, and that the changes seen indicate a differential development for P1-, P2X- and P2Y-purinoceptors. PMID- 2207507 TI - Aging differentially affects direct and indirect actions of endothelin-1 in perfused mesenteric arteries of the rat. AB - 1. The effects of age on the vascular action of endothelin-1 were studied in mesenteric resistance arteries of 4, 9 and 27 month old Fischer 344 rats. 2. Third order branches (about 200 microns in diameter) of mesenteric resistance arteries were dissected free and mounted on glass cannulae in organ chambers. Changes in intraluminal diameter of the perfused and pressurized vessels were continuously measured with a video dimension analyzer. 3. Endothelin-1 (10(-14) - 3 x 10(-8) M) caused contractions that were augmented after removal of the endothelium. The inhibitory effects of the endothelium were greater in young than in old rats. 4. The sensitivity of vascular smooth muscle to endothelin-1 decreased with age, while the maximal response was maintained. In contrast, the contractions to noradrenaline were unaffected by aging. 5. Threshold concentrations of endothelin-1 potentiated the contractions evoked by low and moderate concentrations of noradrenaline (10(-7) - 10(-6) M) in old, but not in young, rats. 6. Endothelium-dependent relaxations to acetylcholine inhibited maximal contractions to endothelin-1 and this effect decreased with age. In contrast, the relaxations to the nitric oxide donor, 3-morpholinosydnonimine (SIN 1; the active metabolite of molsidomine), did not differ in the three age groups. 7. Aging specifically decreases the direct contractile effects of endothelin-1 and the inhibitory effects of the endothelium against these contractions, while the indirect (potentiating) effects of the peptide become more pronounced. PMID- 2207505 TI - gamma-Aminobutyric acid inhibition of histamine-induced inositol phosphate formation in guinea-pig cerebellum: comparison with guinea-pig and rat cerebral cortex. AB - 1. gamma-Aminobutyric acid (GABA), 2 mM, inhibited basal accumulation of [3H] inositol monophosphate ([3H]-IP1) in lithium-treated slices of guinea-pig cerebellum preincubated with [3H]-inositol. In contrast, 2 mM GABA stimulated the accumulation of [3H]-IP1 in rat cerebral cortical slices over a 60 min incubation period, but had no significant effect in slices of guinea-pig cerebral cortex. The estimated IC50 for the inhibitory action of GABA in guinea-pig cerebellar slices was 0.52 +/- 0.12 mM. 2. GABA inhibited histamine-induced [3H]-IP1 accumulation in guinea-pig cerebellar slices in a non-competitive manner. The best-fit value for the maximum level of inhibition was 74 +/- 6%. The estimated IC50 for GABA was 0.77 +/- 0.15 mM and was not significantly different from the IC50 for inhibition of the basal accumulation of [3H]-IP1. The response to histamine in guinea-pig and rat cerebral cortical slices was also inhibited by 2 mM GABA. 3. In guinea-pig cerebellar slices 2 mM GABA potentiated histamine induced [3H]-inositol bisphosphate ([3H]-IP2) accumulation, whereas in both guinea-pig and rat cerebral cortex the effect was inhibition. 4. Isoguvacine and muscimol, GABAA-selective agonists, and (-)-baclofen, GABA(B)-selective, had no significant effect on basal or histamine-stimulated accumulation of [3H]-IPs in guinea-pig cerebellar slices. (-)-Baclofen had only a weak inhibitory effect on [3H]-IP1 accumulation in guinea-pig-cerebral cortex (16 +/- 6% inhibition with 10 microM (-)-baclofen), whereas in rat cerebral cortex (-)-baclofen mimicked the inhibitory effect of GABA. 5. Nipecotic acid (1 mM) had qualitatively similar effects to those of 2mm GABA in guinea-pig cerebellar slices. 6. The competitive GABA uptake inhibitors SK&F 89976-A, SK&F 100330-A and SK&F 100561-A were potent histamine H,-receptor antagonists, as indicated by the inhibition of [3H] mepyramine binding to homogenates of guinea-pig cerebellum and cerebral cortex. 7. GABA (2 mM) caused a small inhibition (12 + 3%) of [3H]-inositol incorporation into total inositol phospholipids in guinea-pig cerebellar slices, as in rat cerebral cortical slices, whereas 0.2mm histamine caused a small stimulation (15 + 4%). In the presence of both GABA and histamine, [3H]-inositol incorporation was unchanged from basal (101 + 5%). 8. GABA also inhibited [3H]-IP1 formation induced by endothelin-1 in guinea-pig cerebellar slices and increased, but not significantly, the amount of [3H]-IP2 accumulated. This, taken with the inhibitory effect on basal and histamine-stimulated accumulation, suggests that the action of GABA in guinea-pig cerebellar slices may be non-selective and may not be exerted through a specific GABA receptor. PMID- 2207508 TI - Psychiatric aspects of the menopause. AB - In the debates about the association between mental illness and the menopause, the psychiatric approach contradicts assertions by the gynaecological and psychoanalytic literature that the menopause has a negative effect on mental health. General population studies show that, if at all, psychiatric morbidity is more common in women in the five years before menopause. Sociocultural and family factors are more important in the aetiology of mental illness in menopausal women than physiological changes. Anxiety and depression in such women do not respond to oestrogen therapy, although some cases respond to antidepressants. PMID- 2207509 TI - The continuum of psychosis and its genetic origins. The sixty-fifth Maudsley lecture. AB - Attempts to draw a line of genetic demarcation between schizophrenic and affective illnesses have failed. It must be assumed that these diseases are genetically related. A postmortem study has demonstrated that enlargement of the temporal horn of the lateral ventricle in schizophrenia but not in Alzheimer-type dementia is selective to the left side of the brain. This suggest that the gene for psychosis is the 'cerebral dominance gene', the factor that determines the asymmetrical development of the human brain. That the psychosis gene is located in the pseudoautosomal region of the sex chromosomes is consistent with observations that sibling pairs with schizophrenia are more often than would be expected of the same sex and share alleles of a polymorphic marker at the short arm telomeres of the X and Y chromosomes above chance expectation. That the cerebral dominance gene also is pseudoautosomal is suggested by the pattern of verbal and performance deficits associated with sex-chromosome aneuploidies. The psychoses may thus represent aberrations of a late evolutionary development underlying the recent and rapid increase in brain weight in the transition from Australopithecus through Homo habilis and Homo erectus to Homo sapiens. PMID- 2207510 TI - Insight and psychosis. AB - The concept of insight into psychosis has received scant attention in the psychiatric literature. Drawing on sources such as phenomenology, clinical research and experimental psychology, it is proposed that insight is not an 'all or-none' phenomenon but is composed of three distinct, overlapping dimensions, namely, the recognition that one has a mental illness, compliance with treatment, and the ability to relabel unusual mental events (delusions and hallucinations) as pathological. A scheme is proposed to standardise the assessment of insights to assist further research. PMID- 2207511 TI - An analysis of social competence in schizophrenia. AB - Twenty-one schizophrenics with prominent negative symptoms were compared with 37 schizophrenics without them, 33 patients with major affective disorder and 20 non patient controls on a battery of measures including a role-play test of social skills, the Social Adjustment Scale, and the Quality of Life Scale. The negative schizophrenics were most impaired on every subscale of each measure, followed in order by the non-negative schizophrenics, affective disorder patients, and non patient controls. The social skill measures were not correlated with positive symptom levels, but were highly correlated with measures of community functioning. The results are consistent with the hypothesis that social dysfunction results from focal deficits in social skills. PMID- 2207512 TI - Sex differences in the familial transmission of schizophrenia. AB - The hypothesis that schizophrenic men have a lower familial risk for schizophrenia than schizophrenic women was tested using the DSM-III-diagnosed samples of the Iowa 500 and non-500 family studies. Survival analyses were used to test for differences in the risk for schizophrenia and spectrum disorders, for sex of proband and sex of relative, controlled for fertility effects and ascertainment bias. Male and female relatives of schizophrenic men had a significantly lower risk for schizophrenia, schizophreniform, and schizoaffective disorders than relatives of schizophrenic women. However, the effect was not significant for the full spectrum nor when analysed by sex of relative. Sex differences in the risk for other psychiatric disorders among relatives of schizophrenic probands were not significant. PMID- 2207513 TI - Problems reported by relatives in a community study of dementia. AB - The supporters of 120 demented elderly people completed rating scales of the frequency and severity of the problems they faced, the amount of strain they experienced and their psychological well-being. Problems and strain increased with the degree of dementia. Problems relating to physical dependency, forgetfulness and inertia were relatively common, while disturbed behaviours were relatively uncommon. Physical dependency and disturbed behaviour were less well tolerated than forgetfulness and inertia, but all problem categories were positively associated with measures of strain. Wives reported more problems and strain than husbands, and co-resident children were under greater strain than children who lived independently. PMID- 2207514 TI - Sex differences in the age of onset of bipolar affective illness. AB - Data from a UK national sample showed differences between the sexes in age specific inception rates for mania. Women had a higher inception rate than men during the middle years. The cumulative admission rates were nearly equal between the sexes. PMID- 2207515 TI - An increase in violence on an acute psychiatric ward. A study of associated factors. AB - The increase in violent incidents on an acute psychiatric ward over a 15-month period was found to be strongly associated with the increase in use of temporary nursing staff (r = 0.63; P = 0.0005). The change in staffing patterns accounted for 39% of the variance in violence. An examination of the characteristics of all patients admitted to the ward revealed that the violent patients were significantly younger, more likely to have been admitted compulsorily and less likely to be depressed than non-violent ones. PMID- 2207516 TI - The patients' view of life in a psychiatric hospital. A questionnaire study and associated methodological considerations. AB - In any assessment of hospital life, the patients' view is indispensable, but there is no generally accepted way of seeking it. In this study, the views of 258 patients in four 'traditional' English psychiatric hospitals were obtained by a questionnaire of 45 items supplemented by freehand comments. Their experience of fellow patients, the staff and the material and institutional aspects of hospital care were explored. Some of the benefits and problems of questionnaire use in this realm are discussed. PMID- 2207517 TI - Puerperal insanity in the 19th and 20th centuries. AB - All patients with puerperal psychosis admitted to the Royal Edinburgh Hospital within 90 days of childbirth during the periods 1880-90 and 1971-80 were compared. The majority of cases in both groups had an affective illness with an acute presentation and a fixed interval of onset. The 19th-century cases had a more florid presentation and a greater length of admission (mean, 151 days) to the hospital than the 20th-century ones (mean, 39 days). The incidence of the disorder rose from 0.34 per 1000 childbirths per year in the 19th-century group to 1.04 in the 20th-century one, but this could be explained by nosocomial factors. Most 19th-century cases occurred in multigravid women, which questions the association of puerperal psychosis with primiparae. PMID- 2207519 TI - A structured programme for out-patient alcohol detoxification. AB - An out-patient alcohol detoxification service based in a psychiatric emergency clinic is described. Of 173 patients referred during the first year, 76 (44%) were accepted for the programme; 60 (79%) of these successfully completed detoxification with no medical complications. Compared with previous years, during the year of operation of the service there was a 50% fall in the number of in-patient admissions for detoxification to the local hospital. We conclude that a structured out-patient detoxification programme is safe and effective, and may obviate the need for many patients to be admitted, freeing psychiatric beds for other uses. PMID- 2207518 TI - Self-poisoning in adolescents. Hospital admissions and deaths in the Oxford region 1980-85. AB - Linked hospital and death records for 10-20-year-olds admitted with a diagnosis of poisoning were analysed. Between 1980 and 1985 there was a significant decline in admission rates, which was mainly attributable to a decline among 16-20-year old females. There was no evidence of a decline in the admission rates among 12 15-year-olds. Ten per cent of the study population had at least one further hospital admission for poisoning during the mean follow-up period of 3.6 years. Female admission rates were substantially higher than those in males but readmission rates, given a first admission, were similar. The death rate in the study cohort was significantly higher than would be expected in the general population of this age and nearly all the deaths were from violent or unnatural causes. PMID- 2207521 TI - Vitamin deficiency and mental symptoms. PMID- 2207520 TI - The effect of moderate weight loss on overnight melatonin secretion. AB - Overnight plasma melatonin level was measured in ten healthy women before and after a 4300 kJ (1000 kcal) diet in which they lost an average 3.1 kg. This weight loss did not significantly alter melatonin levels. PMID- 2207522 TI - Seasonal affective disorder following brain injury. AB - Seasonal affective disorder has not previously been linked with neuroanatomical abnormalities despite its relationship to biological rhythms. A 45-year-old woman is described with an arteriovenous abnormality in the right frontotemporal region who developed recurrent winter depression and summer hypomania. PMID- 2207523 TI - Manic-depressive psychosis in a mentally handicapped person. Seasonality: a clue to a diagnostic problem. AB - Diagnosis of mental illness in mentally-handicapped people is often difficult and complex, because of atypical presentation and lack of clear diagnostic criteria. A patient in whom seasonal variation in behaviour and mood gave a clue to the diagnosis of manic-depressive psychosis is reported. PMID- 2207524 TI - Calcium-channel blockade and depressive illness. PMID- 2207525 TI - Symptomatic trans-sexualism. AB - A 24-year-old male schizophrenic had a delusion that he was female and had lived his life as a woman for almost two years. Unlike the only other reported case, his 'symptomatic trans-sexualism' responded to the effective treatment of his schizophrenia. PMID- 2207526 TI - Erotomania in relation to childbirth. AB - A case of erotomania in relation to childbirth is reported. There was a good response to treatment and no evidence of relapse at 18-month follow-up. PMID- 2207527 TI - Anorexia nervosa and baby gazing. AB - The uncommon behaviour of baby gazing is described in a patient who had also suffered three episodes of anorexia nervosa. The baby gazing responded to joint therapeutic interviews leading to the patient and her husband resolving their different views about having a family and the patient becoming pregnant. Even then there was a minor recurrence of anorexic behaviour which yielded to treatment. PMID- 2207528 TI - Predicting the productive research psychiatrist. PMID- 2207529 TI - Anticholinergics: the consensus statement. PMID- 2207530 TI - Multiple personality disorder. PMID- 2207531 TI - HLA-DR2-frequencies in affective disorders. PMID- 2207532 TI - Glucose metabolic rate in schizophrenia. PMID- 2207533 TI - Failure of progesterone treatment in puerperal mania. PMID- 2207534 TI - Post-traumatic stress disorder. PMID- 2207535 TI - Fetal uropathy. PMID- 2207536 TI - Nuclear techniques for the analysis of urinary calculi. AB - Sections of urinary calculi were prepared and point-by-point analyses along a line-scan were carried out using the techniques of proton-induced X-ray emission (PIXE) and nuclear reaction analysis (NRA). Correlations between several pairs of elements (including trace elements) were noted and it was also clear that the composition of a stone varied markedly at different stages of development. PMID- 2207537 TI - Flexible cystoscopy as an adjunct to extracorporeal shockwave lithotripsy. AB - Ancillary procedures associated with extracorporeal shockwave lithotripsy (ESWL) include placement and subsequent removal of double pigtail ureteric stents. A simple new technique has been developed for the insertion of these stents. Using the flexible cystoscope, the procedure is performed on an out-patient basis under local anaesthesia. Placement of the stents was successful in 30/34 patients and removal was successful in 14/14 patients. PMID- 2207538 TI - Renal carcinoma in a solitary kidney. AB - We studied the clinical and pathological features of 26 patients with renal carcinoma of a solitary kidney, including 6 treated at this hospital. Four patients had a contracted kidney and 22 had previously undergone nephrectomy. Partial nephrectomy was performed in 16 patients, enucleation of the tumour in 5 and radical nephrectomy in 5 because of the size of the tumour. Ex vivo surgery was carried out in 4 patients. The duration of ischaemia ranged from 15 to 365 min but was longer in those who underwent ex vivo surgery (149 to 365 min). Of the 21 patients who underwent partial nephrectomy or enucleation, the serum creatinine level increased (greater than or equal to 2.0 mg/dl) post-operatively in 16 patients, of whom 9 required temporary haemodialysis. No recurrence has been noted in those who underwent partial nephrectomy, but 1 patient who underwent enucleation of the tumour developed a solitary pancreatic metastasis 2 years 6 months after surgery and was treated by a partial pancreatectomy. Kidney preserving surgical procedures are considered to improve the quality of life, but careful follow-up is necessary. PMID- 2207540 TI - Immunofluorescent and histochemical staining confirm the identification of the many diseases called interstitial cystitis. AB - Interstitial cystitis comprises a complex of diseases typified by symptoms of pelvic pain. Functional complaints do not aid the clinician in determining loss of anatomical capacity. Histochemical staining with PAS-colloidal iron/Van Geison's counterstain offers improved diagnostic ability for the pathologist and correlates well with immunofluorescent findings. Four distinct diseases can be identified through immunofluorescent staining, indicating that each is the result of different responses of the urothelium and endothelium to injury. Loss of bladder capacity associated with these diseases can be expected with age, but immunofluorescent staining for IgM within the capillaries of the interstitium is a more sensitive predictor. PMID- 2207539 TI - Use of the double pigtail stent in stone retrieval following unsuccessful ureteroscopy. AB - Insertion of a double pigtail stent is known to cause ureteric dilatation. We analysed the effect of an indwelling double pigtail stent on the success rate of calculus extraction by second ureteroscopy when the initial ureteroscopy fails. Over a 12-month period, a first ureteroscopy failed in 42 patients; 30 were then treated by ureteroscopy combined with a ureteric stent and 12 were treated without a ureteric stent. The group with an indwelling stent had a successful second ureteroscopy or spontaneously passed the calculus in 24 cases (84%) compared with 5 unstented cases (45%). Ureterolithotomy was necessary in 2 patients with a stent and 3 with no stent. It was concluded that following failed ureteroscopic manipulation of calculi, insertion of a double pigtail stent was associated with a higher subsequent success rate for removal of stone by ureteroscopy and a consequent lower rate of ureterolithotomy. PMID- 2207541 TI - Do women with idiopathic sensory urgency have early interstitial cystitis? AB - Interstitial cystitis is rarely considered as a cause of urinary symptoms in referrals to gynaecology clinics. Recent concepts in the diagnosis of this condition mean that it is emerging as a much more common entity, with both early and late forms of the disease being described. Mast cell density in the detrusor muscle has been reported to be useful as a disease marker to substantiate the diagnosis of interstitial cystitis where no classical diagnostic features exist. We assessed mast cell counts in bladder biopsies from 27 women with idiopathic sensory urgency and 10 control patients about to undergo a colposuspension procedure for pure genuine stress incontinence; 30% of the study group had a clear increase in the detrusor muscle mast cell population (detrusor mastocytosis). No control patient showed such an increase. Early interstitial cystitis should be considered as a possible cause of lower urinary tract symptoms in patients with apparently idiopathic sensory urgency. PMID- 2207542 TI - Assessment of residual urine in men following catheterisation. AB - There is a certain volume of urine left within the bladder which cannot be drained by a catheter. A dilutional method was used to calculate this residual volume in 15 men; 10 had acute retention secondary to benign prostatic hyperplasia and 5 had permanent indwelling catheters for neurogenic urinary incontinence. The mean catheterised residual volume was 98.53 ml for patients with acute retention and 14.48 ml for patients with long-term catheters. The explanation for higher post-catheterisation volumes in the acute retention group is probably multifactorial; bladder sacculation and diverticula, detrusor tone and reflux may all play a role. PMID- 2207543 TI - Cell cycling in bladder carcinoma determined by monoclonal antibody Ki67. AB - Current methods of predicting prognosis in transitional cell carcinoma of the bladder fail to provide consistently reliable information about future tumour behaviour. The monoclonal antibody Ki67 recognises an antigen present in actively dividing cells and Ki67 reactivity has been shown to correlate with conventional prognostic indicators in several tumours. In this study, Ki67 antibody was used to determine the proportions of cells undergoing active division in 26 transitional cell carcinomas of the bladder. The proportion of cells stained in muscle invasive tumours (12.3 +/- 5.4%) was significantly greater than in superficial tumours (4.3 +/- 1.9%) and poorly differentiated tumours showed significantly greater proportions of cells staining compared with well or moderately well differentiated tumours. These results show that Ki67 reactivity correlates with high tumour stage and poor differentiation. Ki67 staining provides an easy method of determining tumour cell turnover that might provide additional prognostic information. PMID- 2207544 TI - Superficial bladder cancer in patients under 40 years of age. Efficacy of topical prophylaxis. AB - In patients under the age of 40 years with primary superficial bladder cancer the efficacy of adjuvant topical treatment was the same as in elderly patients (recurrences 23%, progression rate 8%). Patients should therefore be treated on the basis of stage and grade of the tumour regardless of their age. PMID- 2207545 TI - Cobb's collar--a forgotten entity. AB - Cobb's collar or Moormann's ring is a stricture of the bulbar urethra which is largely unrecognised but has considerable relevance urologically as the site of congenital or post-instrumental strictures. The history, anatomy, embryology and surgical importance are reported. PMID- 2207546 TI - Permanent external striated sphincter stents in patients with spinal injuries. AB - Nine patients with complete quadriplegia underwent external striated sphincter stenting with the Wallstent in place of an external striated sphincterotomy. Although suprapubic catheters were placed to provide an outlet should problems develop with the stent, they were successfully removed within 6 weeks in all but 1 patient. Complete bladder emptying with reduced voiding pressures was achieved, together with a significant reduction in the duration of hyper-reflexic contractions. Epithelialisation of the stent was almost complete within 3 months and intermittent catheterisation or endoscopy (and resection) is possible through the stent. Although this is a preliminary report of this new technique, it is hoped that sphincter stenting will provide a rapid, safe and effective method of treating high pressure hyper-reflexia and detrusor sphincter dyssynergia in quadriplegic patients. PMID- 2207548 TI - Pathological classification and follow-up of prostatic lesions initially diagnosed as "suspicious of malignancy". AB - Sections from a series of prostatic specimens (n = 44) in which the initial diagnosis implied a suspicion of malignancy were reviewed and the patients followed up (group 1). The aim was to categorise the morphological appearances according to current criteria and to determine the natural history of any pre malignant lesions within this group. A "control" series of patients (n = 40) in whom the primary diagnosis was benign were also reviewed and their course followed (group 2). The heterogeneity of the abnormalities in group 1 was striking. Of the 44 cases, pre-malignant lesions were seen in 8, microinvasive adenocarcinoma in 11 and lesions not now considered pre-malignant in the remaining 25. None of the 8 patients with pre-malignant lesions developed clinical evidence of carcinoma over a follow-up period of 8 to 12 years. In contrast, 3 of the 11 diagnosed on review as having microscopic invasive adenocarcinoma developed clinically evident tumour within 5 years of surgery. Of the 25 patients whose prostatic lesions were considered benign, 2 developed carcinoma 12 and 13 years after surgery. Only 1 of the 40 patients in group 2 had a pre-malignant lesion and he did not develop tumour within 10 years. However, adenocarcinoma was diagnosed incidentally in 1 patient 3 years after surgery. It was concluded that there is a need to standardise interpretation and reporting of pre-malignant lesions and microscopic foci of adenocarcinoma in the prostate. The limited results on the course of pre-malignant lesions diagnosed incidentally in patients over 60 years of age do not indicate that follow-up would have prompted the early diagnosis of invasive disease. PMID- 2207547 TI - Symptoms versus flow rates versus urodynamics in the selection of patients for prostatectomy. AB - Many prostatectomies are performed on the basis of symptoms alone; 39% of patients referred by their family doctors and 23% of patients who were on waiting lists for prostatectomy of other hospitals, but who had not undergone any urodynamic investigations, were found to be unobstructed on urodynamic criteria. A screening peak urinary flow rate of 12 ml/s or less was associated with urodynamic evidence of obstruction in 95% of cases; 35% of patients with symptoms of outflow obstruction and a flow rate greater than 12 ml/s were also found to be obstructed. One year post-operatively, 84% of patients who were selected for surgery on combined symptomatic and urodynamic criteria were pleased symptomatically with their result. The failure of detrusor instability to resolve following prostatectomy was associated with symptomatic failure of treatment. Residual obstruction was demonstrated in 5 patients who had undergone prostatectomy and were asymptomatic at this time. This study illustrates that objective measures are necessary in the assessment of patients prior to prostatectomy in order to select only patients who are obstructed. The importance of a screening flow rate is emphasised. All patients who underwent surgery had cystometric evidence of obstruction but the symptomatic results of surgery were no better than the results in patients who had been assessed according to non urodynamic selection criteria. We have thus failed to identify a need for routine cystometry in the pre-operative assessment of these patients. Cystometry does, however, have a role in assessing patients with pre-operative flow rates greater than 12 ml/s and in those who remain symptomatic following prostatectomy. PMID- 2207549 TI - Granulomatous orchitis. Review of 15 cases. AB - Granulomatous orchitis is a rare lesion of the testis which can clinically simulate malignancy. The clinical, radiological and pathological features of 15 patients are presented and discussed. PMID- 2207550 TI - Ritual circumcision (Umkhwetha) amongst the Xhosa of the Ciskei. AB - The Umkhwetha is an ancient custom of ritual circumcision still practised by the Xhosa people of Southern Africa. In 45 consecutive youths who required hospital admission the mortality rate was 9%. The complication seen over the years are reviewed and their management discussed. PMID- 2207551 TI - Anterior urethral polyp in a child. PMID- 2207552 TI - Lipomatosis of the ureter. PMID- 2207553 TI - Juxtatesticular seminoma. PMID- 2207554 TI - Epididymal metastasis from prostatic carcinoma. PMID- 2207555 TI - Recent change in a tailgut cyst presenting as urinary retention. PMID- 2207557 TI - Minimally invasive removal of retained ureteric stents. PMID- 2207556 TI - Disappearing staghorns. PMID- 2207558 TI - The endoscopic video camera as an aid to the Stamey procedure. PMID- 2207559 TI - Re: The fate of G3pT1 bladder cancer. PMID- 2207560 TI - Papillary cystic neoplasm of the pancreas: radiological and pathological characteristics in 11 cases. AB - Clinical charts, radiological features, macroscopic and microscopic findings, and clinical follow-up data were retrospectively reviewed in 11 patients with papillary cystic neoplasm of the pancreas (PCNP). The patients were nine women and two men, aged from 13 to 51 years with a mean age of 25 years. The greatest diameter of the PCNPs ranged from 2.5 cm to 14.0 cm with a mean size of 7.5 cm. Six tumours were located in the tail of the pancreas, two in the body and three in the head. Most patients complained of abdominal pain or a mass. Ultrasonographic and/or computed tomography findings showed five solid, four mixed (solid and cystic) and two cystic types of tumour. Angiographically, PCNP was either a hypovascular or mild hypervascular mass with a displacement of the surrounding vessels. No vascular encasement was seen. Macroscopically all 11 tumours consisted of a well defined solid mass with degenerative change of various widths, including haemorrhage, necrosis or dystrophic calcification, and were represented by three radiological types of PCNP. The 11 patients with PCNP survived for from 3 to 253 months after curative resection without any signs of local recurrence or remote metastasis. PCNP usually affects the distal portion of the pancreas of young women. Despite its huge size, PCNP should be explored with aggressive surgical intent because of the inherently good prognosis. PMID- 2207561 TI - Choice of emergency operative procedure for bleeding duodenal ulcer. AB - In a consecutive series of 201 emergency operations in patients with bleeding duodenal ulcer the size of the ulcer was the only factor that showed a significant correlation with the procedure chosen. Vagotomy, pyloroplasty and underrunning of the bleeding point was performed in 101 cases with ten deaths (10 per cent), partial (Billroth II) gastrectomy in 81 cases with ten deaths (12 per cent), and vagotomy and antrectomy in 16 cases with one death (6 per cent). A patient was more likely to be treated by partial gastrectomy if a giant ulcer with an internal diameter of greater than or equal to 2 cm was found. The results suggest that while vagotomy and pyloroplasty, combined with a direct attack on the bleeding point or excision of an anterior ulcer is an acceptable standard emergency operation for bleeding duodenal ulcer, gastric resection proved to be a satisfactory alternative procedure and should be considered in the technically difficult case with a very large ulcer. A giant ulcer was present in 37 per cent of cases coming to surgery. PMID- 2207562 TI - Anterior lesser curve seromyotomy and posterior truncal vagotomy versus truncal vagotomy and pyloroplasty in the treatment of chronic duodenal ulcer. AB - In a prospective randomized controlled clinical trial, anterior lesser curve seromyotomy with posterior truncal vagotomy (AMPT, n = 77) has been compared with truncal vagotomy and pyloroplasty (TVP, n = 69) in 146 patients with chronic duodenal ulcer with a mean duration of symptoms of 7 years. The mean follow-up time was 4.5 years with a range of 2-7 years. One elderly patient died from a myocardial infarction in the TVP group. Acid secretory inhibition in response to insulin and pentagastrin stimuli was equal in both groups, indicating a similar degree of vagal denervation. Recurrent ulcers were more common after AMPT (five) than TVP (two) (P = 0.29, n.s.). Dumping and diarrhoea were significantly commoner (P less than 0.001) after TVP, with 31 instances as opposed to eight with AMPT. The mean operating time was increased by 6 min when AMPT was performed rather than TVP. The results of this study have shown that AMPT is associated with a lower incidence of dumping and diarrhoea and achieves better overall Visick grading. However, continued monitoring is required to assess the long-term incidence of recurrent ulceration after this procedure. PMID- 2207564 TI - Primary gastric carcinoids: a view on management. PMID- 2207563 TI - CA72-4: a new tumour marker for gastric cancer. AB - To date, tumour markers for gastric cancer have proved unreliable. In this study the value of a new serum marker, CA72-4, was compared with the serum activities of carcinoembryonic antigen (CEA) and CA19-9 in a consecutive series of patients with gastric cancer. The results show that the CA72-4 assay is significantly better at separating stage I and II disease from normal controls (P less than 0.01) than CEA (n.s.) or CA19-9 (n.s.). CA72-4 also gave better differentiation between patients with positive and negative nodes (P less than 0.01) and between those who were serosa positive and negative (P less than 0.01). CEA differentiated between patients with positive and negative nodes (P less than 0.05) but CA19-9 could not. CA19-9 and CEA could not discriminate between patients who were serosa positive and negative. In this study, at a specificity of 95 per cent, the sensitivities of CEA, CA19-9 and CA72-4 were 0.25, 0.41 and 0.94 respectively. These preliminary findings indicate that CA72-4 is a reliable tumour marker of disease stage and activity in gastric cancer. Further longitudinal studies are required for full evaluation of its clinical utility. PMID- 2207565 TI - Failure of nutritional recovery after total gastrectomy. AB - Malnutrition is reported to be an inevitable consequence of total gastrectomy, although there are few data to support this contention. Six patients of median age 63 years underwent total gastrectomy for malignancy. At follow-up (median 45 months, range 25-60 months) each patient was clinically tumour-free and underwent dietary assessment, faecal fat and nitrogen measurement and routine haematological testing. Protein and fat stores, measured by neutron activation analysis and the tritiated water dilution technique, were compared with the same measurements made before operation and with predicted values. Mean (s.d.) dietary intake (2224(381) kcal day-1 and 81(15)g protein day-1) met the patients' estimated requirements. Mean(s.d.) serum albumin and faecal nitrogen values were normal but there was notable steatorrhoea (21(17) g day-1). Body composition measurements revealed profound deficiencies of body-weight (P less than 0.02), protein (P less than 0.01) and fat (P less than 0.02) before operation which were not corrected by an apparently curative total gastrectomy (P less than 0.05), although further deterioration was prevented. PMID- 2207566 TI - Gastric outlet obstruction now predicts malignancy. PMID- 2207567 TI - Manometric evaluation of jejunal limb after total gastrectomy and Roux-Orr anastomosis for gastric cancer. AB - Total gastrectomy with Roux-Orr anastomosis is frequently performed for gastric cancer. Since intestinal motility of the Roux limb has never been evaluated after this operation, pressure activity was investigated in the Roux limb of ten patients (aged 51-77 years) who had undergone total gastrectomy and Roux-Orr reconstruction. Investigations were carried out during a 6-h fast and 3 h after a 605 kcal mixed meal. During fasting only two patients had activity fronts and these were abnormal. All ten patients displayed non-propagating bursts of contractions and three had discrete clustered contractions and high amplitude jejunal contractions. The fed state was characterized by a severely reduced motor activity pattern and other abnormalities. Total gastrectomy with Roux-Orr anastomoses provokes a relatively severe disturbance in intestinal activity. PMID- 2207568 TI - Single lumen ileum with myectomy: a possible alternative to the pelvic reservoir in restorative proctocolectomy. AB - An alternative procedure to construction of a pelvic ileal reservoir was assessed which avoids the need for a pouch, while providing an adequate rectal substitute and good continence. Thirty-six female adult beagles were allotted randomly to undergo total colectomy with (a) ileo-anal anastomosis alone, (b) ileo-anal anastomosis with two 15 cm myectomies, (c) ileo-anal anastomosis and myectomy with an ileo-ileal valve, or (d) ileo-anal anastomosis with a duplicated J pouch. The animals were studied before operation and at 4-weekly intervals for 20 weeks after operation. Mortality rates were similar. Ileal compliance was increased significantly by myectomy from 0.64 ml/mmHg (median, interquartile range 0.49 0.78) after ileo-anal anastomosis alone to 1.65 mmHg (1.16-1.93), P less than 0.01, an increase which was maintained. Ileal capacity was also increased both by myectomy and by the J pouch: ileo-anal anastomosis = 85 ml (75-100 ml), ileo-anal anastomosis and myectomy = 139 ml (116-156 ml), ileo-anal anastomosis and myectomy and ileo-ileal valve = 125 ml (range 85-145 ml), ileo-anal anastomosis and J pouch = 130 ml (range 75-165 ml) (P less than 0.01). Bowel function in the other three groups was markedly superior to ileo-anal anastomosis alone. Mean transit time was significantly less after ileo-anal anastomosis, 5.2 h (2.6-8.2 h) than after both ileo-anal anastomosis and myectomy, 10.5 h (9.6-13.9 h), P less than 0.05 and ileo-anal anastomosis and J pouch, 11.0 h (8.4-13.0 h), P less than 0.05, but addition of an ileo-ileal valve did not produce a further increase in transit time, 12.9 h (range 10.5-14.5 h), P = n.s.. Myectomy of single lumen ileum may be a useful alternative to a pelvic ileal reservoir in restorative proctocolectomy. PMID- 2207569 TI - Elective resection for diverticular disease of the sigmoid colon. AB - From 1966 to 1987, 177 consecutive patients were operated on electively for diverticular disease of the sigmoid colon. The indications for surgery were: colovesical fistula (n = 12), suspicion of residual abscess (n = 39), two or more previous attacks of acute inflammation (n = 52), chronic symptoms (n = 72) and suspicion of carcinoma (n = 2). An abscess was found at operation in 76 patients (43 per cent) and this was extracolic with local peritonitis in 52 patients (29 per cent). An unsuspected abscess was found in 25 of the 72 patients operated on for chronic symptoms. Colonic resection with primary anastomosis was performed in 95 per cent of the 177 patients and in 94 per cent of those 52 patients with an extracolic abscess. There were no postoperative deaths and no clinical anastomotic leakages. Long-term results were very good in 85 per cent of the 177 patients and in 82 per cent of the 72 patients operated on for chronic symptoms. The results of this series suggest that a one-stage procedure can be safely performed with some technical precautions in most patients operated on electively for diverticular disease, even if an extracolic abscess is found. The good long term results in patients operated on for chronic symptoms suggest that such symptoms should be taken into account with respect to surgical indications. PMID- 2207570 TI - Gracilis muscle transposition for faecal incontinence. AB - Transposition of the gracilis muscle for faecal incontinence was performed in 13 patients. Six gained satisfactory continence, four were improved, two did not benefit from the operation and one patient died from intercurrent disease before closure of a pre-existing colostomy. Anal manometry compared with a control group showed no alteration in resting and pressure at a median of 35 mmHg (range 5-63 mmHg), whereas maximum squeeze pressure increased from a median of 38 mmHg (range 5-79 mmHg) to 59 mmHg (range 10-143 mmHg) (P = 0.041) which was, however, significantly lower than 130 mmHg (range 81-236 mmHg) in the control group. All patients who benefited from the operation had an increase in maximum squeeze pressure. The ability to retain a viscous fluid in the rectum was measured in seven patients, four of whom had gained satisfactory continence and three of whom had improved continence. They were able to retain a median volume of 200 ml (range 50-225 ml) without leakage compared with 325 ml (range 250-400 ml) in the control group. These patients could retain the maximum amount of viscous fluid for 5-8 min, whereas all control subjects could do so for more than 15 min. It is concluded that, although gracilis transposition never results in normal continence, acceptable continence may be achieved in selected patients provided careful attention is paid to the technical details of the procedure and provided that systematic postoperative exercises are performed. PMID- 2207571 TI - Survey of the use of thrombolysis for acute limb ischaemia in the UK and Ireland. AB - A total of 156 vascular surgeons from the UK and Ireland responded to a postal questionnaire on the use of thrombolysis in acute limb ischaemia. Almost half had used thrombolysis in the previous 12 months. Low dose intra-arterial streptokinase (89 per cent) was the regimen most frequently used, but 33 per cent had used intravenous streptokinase. Detailed results for 103 patients (limb salvage rate 60 per cent, amputation rate 35 per cent, mortality rate 5 per cent) were similar to those of previously published reports. Complications in most series were infrequent, but in the entire survey there were six bleeding-related deaths and one death from anaphylaxis. A total of 67 per cent of surgeons with working experience indicated that selected patients with acute arterial thromboses were most suitable for thrombolysis, particularly if there was no neurological deficit and no run-off for surgical bypass. Distal or late emboli and graft occlusions were regarded as appropriate by some surgeons. This study demonstrated that many vascular surgeons currently use thrombolysis, although sparingly and in selected cases. Patients with acute limb ischaemia should be managed by experienced vascular surgeons who are aware of the new therapeutic alternatives, an ideal supported by almost three-quarters of respondents to this survey. PMID- 2207572 TI - Resympathectomy of the upper extremity. AB - Resympathectomy was performed in 27 patients (eight bilaterally) with ischaemic hand phenomena. An extended operative technique, resecting parts of the second and third intercostal nerves and their surrounding tissue, was used. In all 35 procedures the posterior extrapleural approach was used. Follow-up was from 3 to 12 years. Only the sympathetic ganglia had been removed during the previous surgery by the axillary approach (67 per cent of these patients had had a transient response for between 6 months and 2 years; 33 per cent had had no response at all). A direct subjective improvement was seen after 27 of the 35 reoperations (77 per cent). In 14 patients continuous wave Doppler ultrasound studies were available and showed a significant increase in peak forward frequency after operation (P less than 0.001). From these data it may be concluded that it is possible to obtain a resympathectomy effect, but reoperation should be reserved for special cases for whom survival of digits is essential. PMID- 2207573 TI - Venous stasis and vein lumen changes during surgery. AB - The mechanisms underlying the development of postoperative deep vein thrombosis remain to be fully elucidated. Previous studies have suggested that peroperative venous distension may be a factor associated with venous thromboembolism. In this study we have obtained high resolution ultrasound images of gastrocnemius and posterior tibial veins in 62 patients undergoing a range of general surgical procedures. From these we determined the changes in vein diameter occurring during the operative procedures, in response to induction of anaesthesia, and after completion of surgery. Veins showed no evidence of dilatation in response to the induction of anaesthesia, but by the end of the operative procedure showed distension of 22-28 per cent. Distension was most prominent in the gastrocnemius veins, and lesser distension was observed in the posterior tibial veins. In a series of patients who received an infusion of 1 litre of saline in addition to basal requirements, distension was 57 per cent compared with 22 per cent in the corresponding control group. Intraoperative venous distension is associated with factors that lead to deep vein thrombosis and may be involved in the mechanisms which result in the commencement of deep vein thrombosis. PMID- 2207574 TI - Use of skin graft knife in the treatment of giant perianal condyloma acuminatum. PMID- 2207575 TI - Percutaneous gastrostomy: an alternative endoscopic approach. PMID- 2207576 TI - Cancer of the colon and rectum. PMID- 2207577 TI - Aetiology of venous ulceration. PMID- 2207578 TI - Endoscopic sphincterotomy for bile duct stones in patients with intact gallbladders. PMID- 2207579 TI - Endoscopic sphincterotomy in hepatic hydatid disease open to the biliary tree. PMID- 2207581 TI - T tube intubation in the management of oesophageal fistula. PMID- 2207580 TI - Operative cholangiography in elective cholecystectomy. PMID- 2207582 TI - Use of fresh porcine bowel in surgical training. PMID- 2207583 TI - A randomized controlled trial of oral 5-FU versus placebo in colorectal cancer: results of 10 years observation time. PMID- 2207584 TI - Bile leakage after removal of T tubes from the common bile duct. PMID- 2207585 TI - Endoscopic sclerotherapy: the far and near effects. PMID- 2207587 TI - Pylorus preserving pancreatoduodenectomy: an overview. AB - Pylorus preserving pancreatoduodenectomy (PPPD) was reintroduced 12 years ago. Since that time, over 400 patients have undergone PPPD with approximately 41 per cent having chronic pancreatitis and 54 per cent having pancreatic and other periampullary malignancies. Reported 5-year survivals in this latter group have been comparable to those achieved by the classic Whipple procedure. The postoperative mortality rate in 339 reported patients has been 3.8 per cent. Postoperative morbidity, including delayed gastric emptying, has been similar to that of the classic Whipple operation. However, PPPD has been associated with fewer late problems with dumping, diarrhoea, delayed gastric emptying (8.6 per cent), and marginal ulceration (3.6 per cent). Moreover, most patients undergoing PPPD have been able to return to their preoperative and preillness weight. The additional advantage of decreased operative time makes PPPD an attractive alternative to the classic pancreatoduodenectomy. PMID- 2207586 TI - Surgical aspects of malaria. AB - The spread of drug-resistant organisms and increased international travel makes malaria a disorder of ever-increasing importance. This report reviews those aspects of malaria of surgical relevance. The importance of the spleen in host defence against malaria and other infections makes splenic preservation desirable whenever possible after rupture of the spleen. Tropical splenomegaly is caused by an abnormal immune response to malaria and is best managed medically. Careful selection of blood donors is essential to prevent transfusion malaria, and routine antimalarial prophylaxis is indicated for blood recipients in many endemic areas. The risk of postoperative malaria may justify chemoprophylaxis in certain patients. PMID- 2207588 TI - Operative choledochoscopy: common bile duct exploration is incomplete without it. AB - This paper reviews the reported experience of operative choledochoscopy. Development of choledochoscopes to the currently available rigid and flexible instruments is described. The collected results of both rigid and flexible choledochoscopy are reported. Retained stones occurred in 97 of 2712 stone positive explorations with the rigid choledochoscope (3.6 per cent) and in 35 of 1726 stone-positive explorations with the flexible choledochoscope (2.0 per cent). Choledochoscopy should now be a mandatory part of common bile duct exploration. PMID- 2207589 TI - Management of intrahepatic calculi in Caroli's disease by extracorporeal shock wave lithotripsy. PMID- 2207590 TI - Mucosal intussusception to avoid ascending cholangitis. AB - Many methods have been devised to prevent ascending cholangitis following Kasai's hepatic portoenterostomy for biliary atresia. To investigate the effectiveness of mucosal intussusception in preventing ascending cholangitis, 20 mongrel dogs were randomized to undergo Roux-en-Y cholecystjejunostomy and common bile duct ligation with or without mucosal intussusception. Aeromonas hydrophila was instilled into the gastrointestinal tract. Bacterial cultures were grown from samples taken from the gallbladders and lower jejunum, and blood chemistry and barium studies were performed. The barium studies showed satisfactory lack of reflux in all ten dogs with mucosal intussusception. Only two of them had positive cultures for Aeromonas from the gallbladder 3 days after bacterial instillation into the jejunum. All ten dogs in the control group had positive cultures for Aeromonas from the gallbladder. Our results showed that the mucosal intussusception group had a significantly lower rate of recovery of organisms from the gallbladder compared with the control group when the organisms were instilled into distal intestine (P less than 0.05). The method is worthy of clinical trial as a means of preventing or treating ascending cholangitis. PMID- 2207591 TI - Differing effects of pethidine and morphine on human sphincter of Oddi motility. AB - The aim of this study was to evaluate the effects of morphine and pethidine on human sphincter of Oddi motility. The action of these opioids on the sphincter of Oddi was evaluated by means of intraoperative manometry in 36 patients undergoing elective cholecystectomy. Both opioids were given in intravenous cumulative equipotent doses up to a maximum of 10 micrograms/kg morphine or 100 micrograms/kg pethidine. At these doses, morphine increased the mean(s.d.) frequency of contractions from 2.4(1.0) to 7.9(1.6) (P less than 0.001); this effect was reduced by naloxone (0.04 mg bolus, P less than 0.05). Pethidine inhibited the frequency of contractions from 1.5(0.8) to 0.8(0.5) (P less than 0.05); this response was blocked by atropine (0.6 mg bolus, P less than 0.01). Pretreatment with atropine or naloxone reduced the frequency of contractions significantly (P less than 0.05). The results illustrate different responses to pethidine and morphine of the sphincter of Oddi, and provide a pharmacological explanation for the suitability of pethidine over morphine as the analgesic of choice in patients experiencing biliary pain. PMID- 2207593 TI - Intraoperative ultrasonography and the detection of liver metastases in patients with colorectal cancer. AB - A total of 213 patients with carcinoma of the colon and rectum were examined to detect liver metastases. The study compared preoperative ultrasonography and inspection and palpation of the liver during surgery with intraoperative ultrasonography. Preoperative ultrasonography, inspection and palpation identified 238 metastases in 42 patients. Intraoperative ultrasonography detected 116 previously unrecognized metastatic tumours during 40 surgical procedures (P less than 0.01). High resolution intraoperative ultrasonography is safe and more accurate than preoperative imaging and surgical exploratory methods. The examination is simple to perform and success appears to be related to careful attention to detail. PMID- 2207592 TI - Plasma cell granuloma of the distal oesophagus. PMID- 2207595 TI - Indications for assisted conception. AB - The main assisted conception methods are IVF, GIFT and IUI (all with superovulation). Their choice usually depends not only on their effectiveness but on a balance between the chance of conceiving naturally or with simpler treatments, relative cost-effectiveness, and the woman's age. IVF is also useful in the diagnosis of fertilizing ability when there is sperm dysfunction. This paper therefore describes and rationalizes the context in which assisted conception is to be applied in terms of the frequency, diagnosis and results of standard treatment of the various causes of infertility. PMID- 2207594 TI - Development of assisted conception. AB - Advances in assisted human conception in the last twenty years were founded on the detailed knowledge of the mammalian reproductive cycle gained in the earlier years of this century. Several lines of study coincided in the 1960's, including the use of ovarian stimulants to regulate follicle growth, oocyte maturation and ovulation, fertilization and embryonic growth in vitro, and the introduction of safer and better methods of laparoscopy. A combination of these techniques with embryo replacements in the uterus permitted the introduction of IVF for the alleviation of infertility. In turn, these methods were extended to other forms of assisted conception, including GIFT, which gave a wider choice of methods for the treatment of specific causes of infertility. Advances during the last decade include rapid progress in the use of ultrasound, the introduction of the LHRH agonists in new forms of stimulation, embryo cryopreservation, and micromanipulative techniques on oocytes and embryos for the alleviation of male infertility and the diagnosis of genetic disease in preimplantation embryos. PMID- 2207596 TI - Induction of multiple follicular development for IVF. AB - It is now accepted, almost universally, that multiple follicular development is a pre-requisite for a successful assisted conception programme. The reasons for this are based on abundant clinical evidence from the major IVF and GIFT centres of the world indicating the benefits of having multiple gametes available for transfer. The more embryos transferred, the better the pregnancy rate; the more embryos available for cryopreservation the better the chances of subsequent survival and replacement. However, the vast majority of patients in IVF/GIFT programmes have normal ovarian and pituitary function designed to produce a single dominant follicle and oocyte each month. Obtaining multiple follicular growth requires pharmacological manipulation of ovarian function and complicating factors may arise from both ovarian and pituitary sources. Methods employed to achieve multiple follicular growth vary considerably in the different centres and experiments continue in attempts to find either the simplest or the perfect system, or both. This would provide abundant oocytes and the ideal hormone environment for implantation, with no interfering factors at either the ovarian or endometrial level, while avoiding the drawbacks commonly encountered such as pre-operative ovulation or hyperstimulation syndrome. It should also be inexpensive, although in reality cost-effectiveness is more important. PMID- 2207597 TI - Endocrine monitoring for assisted human conception. AB - The pregnancy potential of an assisted conception treatment cycle increases with the number of oocytes or embryos returned to the patient. It is therefore necessary for the patient to undergo a form of follicular stimulation which will result in the recruitment of a cohort of preovulatory follicles and hence supernumerary oocytes. The commonest superovulation regimen used consists of clomiphene citrate combined with human menopausal gonadotrophins. However the administration of these stimulants increases circulatory levels of LH and perturbs the normal feedback systems of the hypothalamus-pituitary-ovarian axis leading to an attenuation of the endogenous LH surge. The normal and synchronous development of the uterine endometrium may also be impaired which could lead to a failure of implantation. These inherent problems mean that rapid endocrine monitoring facilities are mandatory for optimizing the outcome of the cycle. Recent use of GnRH analogue agonists which effectively reduce tonic levels of LH and inhibit the surge have brought about a significant improvement in pregnancy outcome. However some endocrine monitoring is required even after pituitary desensitisation in order to reduce the incidence of the ovarian hyperstimulation syndrome. PMID- 2207599 TI - Evaluation of human sperm function. AB - Our understanding of the causes of male infertility and our ability to develop an appropriate range of diagnostic tests are both dependent upon a knowledge of the cellular mechanisms responsible for the regulation of human sperm function. This review examines the intra- and extracellular factors regulating four separate components of human sperm function: sperm transport, sperm-egg recognition, the acrosome reaction and sperm-oocyte fusion. Within each of these areas the fundamental nature of the process, the control mechanisms involved, the availability of appropriate diagnostic tests and the relationship with human infertility have been considered. PMID- 2207598 TI - Laboratory techniques for handling gametes and embryos. AB - This review describes some basic and novel principles pertaining to the science of in vitro fertilization and embryo culture. Several systems for cell-free culture of gametes and embryos are described. The advantages of a coculture or helper cell system was investigated in several clinical trials using bovine cells from the reproductive tract. Improved embryonic morphology and implantation indicate that standard IVF culture provides suboptimal conditions. Microsurgical methods for assisting in vitro fertilization in cases of severe male factor infertility are also discussed. Thus far, it has been demonstrated that mechanical opening of the zona pellucida by methods such as partial zona dissection enhances fertilization. In addition, the introduction of a limited gap in the zona seems to facilitate hatching of the blastocyst, which may benefit all patients undergoing in vitro fertilization. PMID- 2207600 TI - Oocyte maturation, fertilization and embryonic growth in vitro. AB - As the oocyte develops into an embryo, cytological and metabolic events follow one another in an accurate and successive sequence. Meiosis resumes in the ovarian follicle, parallel to cytoplasmic and membrane maturation, from the onset of the ovulatory LH discharge. Only a fully mature oocyte will be recognized and penetrated by a fertilizing sperm, to ensure rapid and synchronous male and female pronuclear growth and early embryonic development. In vitro, the resumption meiosis is easily obtained once the oocyte is withdrawn from the inhibitory influence of the follicle. Cytoplasmic and membrane maturation may however be impaired, leading to fertilization failures or anomalies such as triploidy and even impaired embryo viability. Human in vitro fertilization is nowadays routinely carried out with a high success rate, but in vitro embryonic growth to the blastocyst is still unsatisfactory even with oocytes matured in the ovary, and major improvements are needed to reach optimal viability. Many studies have now been published on human oocyte maturation, fertilization and the growth of embryos in vitro. We give only a brief account of them, due to limited space, and have therefore included topics of most relevance to assisted conception as opposed to those more involved with academic research. PMID- 2207601 TI - Cryopreservation. AB - Embryo cryopreservation is now firmly established as a routine component of in vitro fertilization (IVF) and other assisted conception techniques for the resolution of human infertility. Excess fertilized oocytes and embryos can be preserved for infertile couples avoiding the necessity to replace large numbers of embryos which reduces the incidence of multiple births and their sequelae. The additional pregnancies obtained from replacement of cryopreserved embryos has effectively increased the success rate of a cycle of IVF treatment for a couple by 1 to 10%. There is an increasing preference to cryopreserve fertilized pronuclear oocytes by slow cooling in 1,2-propanediol (PROH) although many clinics also cryopreserve early cleavage stage embryos by slow cooling in PROH or dimethyl sulphoxide (DMSO) with similar success rates to those for pronuclear oocytes. Numerous problems have appeared with the attempted cryopreservation of mature unfertilized oocytes, including nonreversible disassembly of the meiotic spindle during cooling, reduced fertilization rates due to the effects of cryoprotectants and cooling on the zona pellucida, parthenogenetic activation of oocytes by PROH, substantially increased polyploidy and aneuploidy when frozen thawed oocytes are fertilized and increased cryoinjury to unfertilized oocytes when compared to fertilized oocytes. It is also necessary to address problems which have arisen through the disagreement of separated couples about the disposition of embryos in cryostorage. PMID- 2207603 TI - Assessment of endometrial differentiation and function. AB - The failure to produce an endometrium which is receptive and able to support implantation may underlie some cases of infertility and represent a contributory factor preventing higher pregnancy rates in IVF. This is of direct relevance to ovarian hyperstimulation protocols which may affect the pattern of endometrial differentiation and function and to patients possessing intrinsic defects in their endometrial response. It is apparent that markers of endometrial differentiation are required, particularly those defining the ability of the tissue to support implantation. The common method of assessing endometrial differentiation by histological evaluation, which has been substantially improved by techniques of morphometric analysis, depend upon alterations in endometrial structure. However, the production of monoclonal antibodies to proteins and epitope-bearing mucins which exhibit specific patterns of expression during the luteal phase now also enables immunohistological assessment of endometrial differentiation. Whether these proteins mediate essential functions is not known but as they represent end-points of hormone action this would suggest that their measurement may form the basis of tests of endometrial function and supplement morphometric analyses. PMID- 2207602 TI - Endocrinology in luteal phase and implantation. AB - The normality of the luteal phase after superovulation depends on the method and adequacy of the stimulation regimen. In comparison with natural cycles, the luteinisation of multiple follicles produces higher concentrations of steroids in blood, and soon after ovulation a correct ratio of serum oestradiol (E2) to progesterone is critical to establish viable pregnancies. Out of phase and asynchronous endometria can arise after stimulation with clomiphene (CC) alone or in association with human menopausal gonadotrophin (HMG), and pregnancies mostly arose in patients with advanced endometrial characteristics and elevated post ovulatory levels of serum progesterone after HMG stimulation. Increasing plasma progesterone concentrations in the early luteal phase with natural progesterone can thus be considered as a rational approach to improve rates of implantation. Premature luteal regression is frequently observed after HMG stimulation whether or not in association with gonadotrophin releasing-hormone agonists (GnRHa). Support to the theca lutein cells is mandatory before sufficient human chorionic gonadotrophin (HCG) is produced by the embryo. Deficient luteal phases can be treated with hormonal support, but the efficacy of routine luteal supplementation after ovarian hyperstimulation has still to be proven in larger controlled trials. PMID- 2207604 TI - Value of ultrasound during the menstrual cycle and early pregnancy. AB - Ultrasound is a recently introduced technique that allows repeated noninvasive imaging of the uterus, ovaries and associated structures. It offers a relatively simple method for the repeated examination of the abdominal organs including growing fetuses, and is increasingly being used to measure blood flow in the identification of disease states. The clinical applications of real time pelvic ultrasonography are principally in the field of gynaecology to assess anatomical normality, and to monitor the progress of natural and stimulated cycles in assisted reproductive techniques. Once infertility treatment has been successful, ultrasound has proved to have a great value, when combined with established endocrinological parameters, to monitor the development of pregnancy, and the normality of fetal growth. PMID- 2207605 TI - Outcome of pregnancies resulting from assisted conception. AB - With the increasing practice of assisted conception, the health of the resulting children is becoming an increasingly important issue. Experience with four thousand children conceived by IVF or GIFT indicates that multiple pregnancy, which frequently results from assisted conception, is the main determinant of complications during pregnancy and of the health of the children at the time of birth. Overall malformation rates are similar to those in the country as a whole. There are, however, still insufficient numbers of children studied to draw firm conclusions about the risk of specific types of malformations. This will require the continued monitoring of children resulting from assisted conception, and the continued co-operation of many individuals and centres practising assisted conception. PMID- 2207606 TI - Factors affecting the outcome of assisted conception. AB - In order to assess the major biological and clinical factors which influence the outcome of both IVF and GIFT, the results of a large GIFT series performed in this unit have been analysed over a time interval when two different policies have been in force as to the number of oocytes that should be transferred. The reason for using GIFT data, as opposed to IVF, is simply because it is more difficult to adversely affect the outcome of GIFT treatment, as opposed to IVF, and hence this allows more critical appraisal and interpretation of results. The GIFT series to be described was conducted between March 1986 and October 1987, when a flexible policy on the number of oocytes for transfer was in operation. Since then a fixed policy has been in force at the request of the Hospital's Ethics Committee and the Voluntary Licensing Authority (now the Interim Licensing Authority), whereby three, or exceptionally four, oocytes are transferred irrespective of individual patient's circumstances because of concern about the relative risk and sequelae of multiple pregnancy and selective reduction of pregnancy. I still believe, however, that some infertile couples have a lower chance of pregnancy with assisted, or natural conception and also a lower risk of multiple pregnancy and that it is therefore important to assess the biological and clinical factors influencing fecundity in order to formulate appropriate treatment policies. PMID- 2207607 TI - Simple techniques past and present as an alternative to in-vitro fertilization and GIFT. PMID- 2207608 TI - Oocyte donation and surrogacy. AB - Oocyte donation offers the prospect of achieving a successful pregnancy to a group of patients traditionally considered to be irreversibly sterile. In patients with ovarian failure, it is possible to create an endometrial milieu that is receptive to embryonic implantation by giving exogenous steroid replacement. A high fertility potential can be achieved with a low miscarriage rate in oocyte recipients irrespective of the patient's age. This reflects the improved biological performance of oocytes obtained from young donors. In oocyte recipients, it is now feasible to dissociate the stages of embryonic development and endometrial maturation. Hence, oocyte donation can provide insights into as yet unresolved questions such as the duration of the 'implantation window' in humans. Oocyte donation will undoubtedly complement basic IVF in trying to elucidate the biological interactions between the conceptus, endometrium and steroid environment in human reproduction. PMID- 2207609 TI - Using a donor insemination management system. AB - A computerized database management system has been developed for an expanding donor insemination service. The programs have been written in dBASEIV language and they will run on a single personal computer (IBM or compatible, with a hard disc) or on a network. The central database enables access to stock, donor and couple details and routine statistics e.g. pregnancy rates, although levels of access to the system are restricted by password control. The central database provides an archival component, with data recorded on a daily basis, a service management component assisting in the routine administration of a donor insemination service, a financial component and a statistical component providing for both local and national statistics. Data may be converted for use in other software packages, e.g. SPSSX, SAS (statistical packages), encouraging data manipulation and enabling specific research questions to be addressed more readily. PMID- 2207610 TI - Future developments in IVF. AB - Among the many potential developments in IVF, four topics are chosen for discussion. New concepts in the regulation of follicle growth should permit the introduction of improved methods of ovarian stimulation, eg through the use of LHRH antagonists or growth factors. Detailed analyses on human capacitation, the nature of sperm-egg binding and sperm maturation in the epididymis will assist the treatment of male infertility. Research on embryos will clarify details of the growth and metabolism of embryos and their cryopreservation, and indicate the preferred methods to diagnose genetic disease in preimplantation embryos. Analyses on embryonic growth to day 10 and beyond, on interactions between uterine stroma and epithelium, and between these tissues and the trophoblast, should clarify the physiology and biochemistry of human implantation. PMID- 2207611 TI - Counselling, care in infertility: the ethic of care. AB - Infertility is a health-care problem which has very definite physiological, psychological and social implications. Infertile couples are continually reminded of their plight--the structure of society is based on the family unit; simple activities such as shopping are a constant reminder, the shops being geared to the family; the neighbours fill their cars with all the paraphernalia which accompanies children--the stigma of infertility often leads to mental disharmony, marital difficulties, divorce, and in some cultures to ostracism. The suffering experienced by infertile people is very real. We need to remind ourselves that we are treating 'people who are infertile' rather than 'infertility'. Our care goes beyond their physical treatment--their stresses and strains are our concern and we must be careful not to add additional stress to their existing problems. Successful treatment can transform their lives: 'They are bright, healthy, beautiful children--a dream come true. Our lives are transformed and complete. Thank you a million times.' Failure after years of trying is all the more painful. The availability of effective, informed, independent and involved counselling is essential. PMID- 2207612 TI - Ethics and the law: the law and assisted human conception. AB - This article aims to provide no more than a brief summary and overview of some of the principal legal questions which arise in connection with assisted human conception. There is no requirement of legal suitability for natural parenthood, though a child may be removed from parental care at birth if its welfare is considered to be at risk. Where medical or other assistance is required, however, the law and social judgments may impinge on the freedom of individuals to procreate. Commercial surrogacy has recently been criminalized, but private surrogacy arrangements without reward are not illegal--although any contract would probably be unenforceable through the courts. If medical intervention is required to achieve assisted conception, the availability of resources for NHS treatment, the physical and mental health of the prospective mother and father, and the welfare (or lack of it) of any prospective child, may be factors in deciding whether an infertility unit will offer treatment. Such practices must not operate unfairly and must not discriminate on racial grounds. If treatment is provided, and a woman becomes pregnant, the ordinary abortion laws will apply and, it is thought, will extend to the selective reduction of a multiple pregnancy--there is no claim in English law for 'wrongful birth'. AID does not constitute adultery, and the law has recently been reformed to recognize children born following AID as legitimate to their social parents. A child may be regarded as the legitimate child of a surrogate mother's marriage, but where the baby is genetically distinct from the surrogate mother, the law, and is uncertain and as yet could be conflicting claims of parenthood without legislation. The storage and disposal of human gametes and embryos may raise problems of 'ownership'. PMID- 2207613 TI - Evidence for degeneration of retinal W cells following early visual cortical removal in cats. AB - Size and distribution of ganglion cells surviving unilateral visual cortical removal at 5-7 days of age were examined in domestic cats. Such lesions were expected to result in a substantial loss of X cells in ipsilateral temporal and contralateral nasal retina, leaving ipsilateral nasal and contralateral temporal retina to serve as intact controls. A computer model of normal retinal ganglion cell topography was used to make qualitative predictions of the distribution of surviving ganglion cells. Contrary to expectations, a visual streak was no more prominent in the distribution of surviving cells than in the distribution of the normal ganglion cell population. The magnitude of ganglion cell loss, furthermore, was at least twice as great in nasal retina as in temporal retina. In nasal retina, the cell loss extended well into the small-medium size range, while in temporal retina, cell loss was restricted to the large-medium size range. Taken together, the differential magnitude of cell loss in nasal and temporal retina and the greater loss of small-medium cells in nasal retina cannot be explained by the exclusive degeneration of X cells and suggest that many of the degenerated ganglion cells were medium-sized W or gamma cells. These cells, therefore, share the susceptibility of retinal X cells to early cortical ablation. Surviving gamma cells in both nasal and temporal retina appeared to increase in soma size which may explain why their decreased numbers were not detected in previous physiological studies. Alpha cells, at least in nasal retina, decreased in some size. PMID- 2207614 TI - Synodontid catfish: a new group of weakly electric fish. Behavior and anatomy. AB - Three species of synodontid catfish can produce weak biphasic electric discharges in either continuous or burst-like fashion. The peak-power frequency of these electric organ discharges is around 100 Hz. The electric organ appears to have originated from a sonic muscle: the organ lies dorsal to the swim bladder, contains modified muscle tissue, and is innervated from a motor nucleus located in the caudal medulla. It is possible that synodontid catfish use electric signals in communication and/or object detection. PMID- 2207615 TI - The role of the left and right thalamus in language asymmetry: dichotic listening in Parkinson patients undergoing stereotactic thalamotomy. AB - Fourteen patients with Parkinson's disease (rigidity and unilateral tremor as main symptoms) were treated with stereotactic thalamotomy. The operation was performed in either the left or right ventrolateral thalamus, depending on which hand (or foot) was most affected with tremor. Nine patients were operated on the left side and four on the right side. All patients were tested for asymmetry of language functioning with dichotic presentations of consonant-vowel (CV) syllables. The patients had to indicate which of the two syllables he/she heard on each trial. Dichotic listening was performed before and after the operation, as well as during electrical stimulation of the VL nucleus just before the lesion was carried out. The results revealed essentially three things: an overall reduced right ear advantage (REA) in the patient group compared to what is known from studies of healthy individuals; an increase in REA during left-sided stimulations; and a marked reduction in REA after left-sided lesions. It is concluded that the present data support the notion put forward by Ojemann (e.g., 1975) of a lateralized activating gating mechanism in the left VL nucleus that gates access for language information to the appropriate cortical areas. The gating mechanism seems to be activated by stimulation, and deactivated after lesions. Dichotic listening may thus be a heuristic instrument in assessment of language functions in Parkinson patients. PMID- 2207616 TI - Hemispheric involvement in shadowing vs. interpretation: a time-sharing study of simultaneous interpreters with matched bilingual and monolingual controls. AB - A time-sharing study used shadowing and interpretation/paraphrasing tasks to evaluate lateralization in professional interpreters individually matched to bilingual and monolingual controls. A two-step multivariate general linear model procedure was used to determine lateralized effects and extent of disruption produced by the tasks. Results revealed the monolingual group to be left lateralized for both tasks, but the two bilingual groups were lateralized in the LH only for shadowing. The monolingual group was significantly different from the bilingual groups in the pattern of hand asymmetry for interpretation/paraphrasing. The findings replicate outcomes of prior repeated measures analysis of variance procedures on percentage of change scores. However, new information is added by the more refined analysis. The findings are also discussed in terms of previous laterality studies using similar tasks and subject samples. PMID- 2207617 TI - Speech lateralization in deaf populations: evidence for a developmental critical period. AB - Cerebral lateralization for speech in right-handed normal hearing and deaf adolescents was assessed using the dual-task paradigm. Subjects with normal hearing and deafness acquired after 3 years of age displayed left hemispheric dominance for speech production, whereas both congenitally deaf and those with an early acquired deafness (onset 6-36 months) showed atypical, anomalous cerebral representation. These results suggest the presence of a developmental critical period for cerebral lateralization during which exposure to adequate environmental stimulation may be needed to activate left hemispheric dominance for speech. PMID- 2207618 TI - Retrieval of nouns and verbs in agrammatism and anomia. AB - The ability of five agrammatic and five anomic aphasic patients to produce nouns and verbs was assessed in four tasks. Target words were form class unambiguous, frequency and length matched nouns and verbs, elicited as single words in picture naming and naming-to-definition tasks. The same unambiguous verbs were targets in an action description task. Narrative speech was obtained from each patient using a story elicitation procedure. Agrammatic aphasics produced significantly fewer verbs than nouns, relative to other groups, in all tasks. Anomic aphasics reliably produced more verbs than nouns in naming to definition. These results replicate previous findings for Italian-speaking patient groups, and for several individual cases. In addition, these results extend the relative verb deficit among agrammatic patients to connected speech tasks. Results are interpreted in light of current models of lexical and sentence production. PMID- 2207619 TI - Deep dysphasia: analysis of a rare form of repetition disorder. AB - "Deep dysphasia" is the parallel in repetition to the reading impairment deep dyslexia. Our patient, S.M., showed part of speech, word/nonword, and concreteness effects in repetition, and he made semantic errors, but his oral reading was relatively spared. Further testing indicated that S.M. did not have difficulty perceiving spoken stimuli or deciding their lexical status, but he was deficient at semantically processing spoken words. Moreover, his phonemic memory was severely impaired. We argue that the routes for repetition (lexical and nonlexical) that function without semantic mediation were defective and that deficits in phonemic memory further diminished their effectiveness, since initial phonological encoding of spoken words was not available to guide the output stages of phonological processing. In addition, the semantically mediated route for repetition was unreliable because semantic processing was faulty and S.M. could not accurately label concepts. PMID- 2207621 TI - Pretrial EEG coherence as a predictor of semantic priming effects. AB - Twenty subjects were presented 240 randomized trials of a lexical decision task (LDT) while connected to a 16-electrode EEG montage. EEG data were acquired for 2 sec prior to the onset of each LDT trial. Alpha (9-13 Hz) coherence, alpha power, and 3- to 30-Hz power from five different combinations of EEG electrodes were used to predict semantic effects in the LDT trials. High pretrial coherence in the Right Hemisphere and Left Posterior-Parietal regions was associated with greater semantic facilitation (faster reaction times) in related-prime trials and greater semantic inhibition (slower reaction times) in unrelated-prime trials, relative to neutral-prime trials. No power variables were associated with semantic effects. Results support an information flow model of the functional significance of EEG coherence to cognitive processing. PMID- 2207620 TI - Temporal dimensions of consonant and vowel production: an acoustic and CT scan analysis of aphasic speech. AB - This study explored a number of temporal (durational) parameters of consonant and vowel production in order to determine whether the speech production impairments of aphasics are the result of the same or different underlying mechanisms and in particular whether they implicate deficits that are primarily phonetic or phonological in nature. Detailed analyses of CT scan lesion data were also conducted to explore whether more specific neuroanatomical correlations could be made with speech production deficits. A series of acoustic analyses were conducted including voice-onset time, intrinsic and contrastive fricative duration, and intrinsic and contrastive vowel duration as produced by Broca's aphasics with anterior lesions (A patients), nonfluent aphasics with anterior and posterior lesions (AP patients), and fluent aphasics with posterior lesions (P patients). The constellation of impairments for the anterior aphasics including both the A and AP patients suggests that their disorder primarily reflects an inability to implement particular types of articulatory gestures or articulatory parameters rather than an inability to implement particular phonetic features. They display impairments in the implementation of laryngeal gestures for both consonant and vowel production. These patterns seem to relate to particular anatomical sites involving Broca's area, the anterior limb of the internal capsule, and the lowest motor cortex areas for larynx and tongue. The posterior patients also show evidence of subtle phonetic impairments suggesting that the neural instantiation of speech may require more extensive involvement, including the perisylvian area, than previously suggested. PMID- 2207622 TI - Cerebral lateralization in simultaneous interpretation. AB - Cerebral asymmetries for L1 (Italian), L2 (English), and L3 (French, German, Spanish, or Russian) were studied, by using a verbal-manual interference paradigm, in a group of Italian right-handed polyglot female students at the Scuola Superiore di Lingue Moderne per Interpreti e Traduttori (SSLM-School for Interpreters and Translators) of the University of Trieste and in a control group of right-handed monolingual female students at the Medical School of the University of Trieste. In an automatic speech production task no significant cerebral lateralization was found for the mother tongue (L1) either in the interpreting students or in the control group; the interpreting students were not significantly lateralized for the third language (L3), while weak left hemispheric lateralization was shown for L2. A significantly higher degree of verbal-manual interference was found for L1 than for L2 and L3. A significantly higher disruption rate occurred in the meaning-based mode of simultaneous interpretation (from L2 into L1 and vice versa) than in the word-for-word mode (from L2 into L1 and vice versa). No significant overall or hemispheric differences were found during simultaneous interpretation from L1 into L2 or from L2 into L1. PMID- 2207623 TI - Typicality effects in artificial categories: is there a hemisphere difference? AB - In category classification tasks, typicality effects are usually found: accuracy and reaction time depend upon distance from a prototype. In this study, subjects learned either verbal or nonverbal dot pattern categories, followed by a lateralized classification task. Comparable typicality effects were found in both reaction time and accuracy across visual fields for both verbal and nonverbal categories. Both hemispheres appeared to use a similarity-to-prototype matching strategy in classification. This indicates that merely having a verbal label does not differentiate classification in the two hemispheres. PMID- 2207625 TI - Thermal effects on long-term potentiation in the hamster hippocampus. AB - Extracellular CA1 pyramidal cell activity was measured at different temperatures in hippocampal slices from the Syrian hamster (Mesocricetus auratus), a hibernator. Control records taken before and after tetanic stimulation of Schaffer collateral/commissural pathways were compared to determine if long-term potentiation (LTP) was established. LTP (an enhancement of the population spike amplitude or population synaptic response following tetanus) was elicited in slices at temperatures above 22 degrees C, but not in slices at temperatures of 20 degrees C. When LTP was established at temperatures above 24 degrees C, however, lowering the temperature to 20 degrees C did not abolish the LTP. Furthermore, when a tetanus was delivered at 20 degrees C and the bath temperature was then raised above 22 degrees C, LTP was established. These results for step changes in temperature suggest that the sequence of cellular mechanisms leading to LTP is activated, but then arrested in slices maintained at a constant temperature of 20 degrees C. Assuming this type of activity in the slice parallels in vivo hippocampal activity, it follows that the ability to elicit LTP in CA1 hippocampal pyramidal cells is lost when the core temperature of an animal entering hibernation falls to 20 degrees C. PMID- 2207624 TI - Robust synaptic plasticity of striatal cells following partial deafferentation. AB - Partial ablation of the cerebral cortical input to the neostriatum generates a rapid lasting effect on the size of remaining synaptic sites. The neocortex was lesioned in adult rats and the neostriatum was analyzed for effects on remaining spines of principal cells during the period from 2 to 40 days. There was an increase in the size of spine heads, boutons and synaptic contact sites. The spine heads became very complex and a corresponding bouton enlargement was accompanied by an increase in the number of synaptic vesicles. By two days, the average profile length of postsynaptic membrane densities (PSDs) had increased by 25% representing an equivalent 50% increase in synaptic contact area. The number of synaptic sites was reduced on each principal neuron of the lesioned group. Comparison of the number of sites per unit volume to their average contact area revealed a reciprocal relationship indicating a conservation in the total synaptic contact area on each neuron. This effect was consistent for all postsurgical days. The lack of a significant return of synaptic number by 40 days indicates that axonal sprouting is not a major factor in neuronal plasticity in the adult striatum. The rapid increase in the size of spines, boutons and synaptic sites at remaining connections suggests that dendrites are the first to initiate the plasticity response in adult neurons through postsynaptic attachments and their corresponding receptor structure. The underlying mechanism of this plasticity may be through a conservation of macromolecules forming postsynaptic membrane specializations on target neurons. Remaining axons appear to follow the dendritic response with a plasticity generating presynaptic appositional specializations to match the contact area of the postsynaptic site. PMID- 2207626 TI - The antinociceptive effects of SCH-32615, a neutral endopeptidase (enkephalinase) inhibitor, microinjected into the periaqueductal, ventral medulla and amygdala. AB - The local effects of SCH-32615, an inhibitor of enkephalinase (EC 3.4.24.11) on the hot-plate (HP) and tail-flick (TF) responses were examined following unilateral intracerebral microinjection into the periaqueductal brain (PAG), the medial ventral medulla (VM) and bilateral microinjection into the amygdala (AM) of the rat. In the PAG and VM, SCH-32615 resulted in a dose-dependent increase in HP and TF response latencies over a dose range of 1-30 micrograms with the ED50 values (micrograms) being PAG-TF = 17; PAG-HP = 11; VM-TF = 7; VM-HP = 6. In the AM, dose-dependent increases were only observed on the HP. (ED50 (micrograms) HP = 17). Peak effects were observed within 10 min and response latencies remained elevated for 45-60 min. Injections of SCH-32615 at sites outside of the PAG or VM were considerably less effective. All antinociceptive effects were antagonized by naloxone (1 mg/kg, i.p.). Twenty-four hours following the microinjection of beta funaltrexamine (an irreversible opioid antagonist) into the PAG or the VM, the effects of SCH-32615 in the PAG were virtually abolished while in the VM, its effects were only moderately reduced. These data suggest that in the presence of a strong thermal stimulus, the behavioral response is subject to a tonically active or stimulus-evoked modulation by the local release in the PAG, VM and AM of an agent, presumably an enkephalin peptide, the degradation of which is altered by enkephalinase inhibition. PMID- 2207627 TI - Neuronal and microvascular alterations induced by the cholinergic toxin AF64A in the rat retina. AB - The choline analogue ethylcholine mustard aziridinium ion (AF64A) produces both neuronal and non-neuronal alterations in the rat retina. The possible involvement of the retinal capillaries in the origin of the apparently non-specific lesions has been investigated. Two hours after a single intraocular injection of 5 nmol AF64A, ultrastructural alterations were observed in neurons of the inner nuclear layer and the ganglion cell layer, where cholinergic cells are located. One week later, the number of cholinergic neurons, identified by choline acetyltransferase immunohistochemistry, was decreased to 65% of control, the neurons located in the inner nuclear layer being more sensitive than those in the ganglion cell layer. The same dose of AF64A also induced ultrastructural changes in retinal capillaries, which showed a significant increase in the number of pinocytotic vesicles and microvilli in the endothelial cells, 2-5 h after the toxin administration. One day later, arterioles and capillaries presented contracted profiles and the lumen was occasionally lost. The sensitivity of endothelial cells to the toxic effects of AF64A may be explained by the presence in the cerebral endothelium of a choline transport mechanism with an affinity close to that of cerebral synaptosomes. In vitro, both neuronal and endothelial choline uptake systems were equally sensitive to the toxin inhibitory effect. The early and severe vascular alterations induced in the retinal microvessels by AF64A may produce changes in blood perfusion and capillary permeability that could account for the apparently non-specific histological damage. PMID- 2207628 TI - Volume regulation in response to hypo-osmotic stress in goldfish retinal ganglion cell axons regenerating in vitro. AB - Goldfish retinal ganglion cell (RGC) axons regenerating in vitro were used to investigate the volume regulatory response to hypo-osmotic stress. Reducing the tonicity of the bathing medium to half strength caused an immediate swelling of axons; however, within 1 min a progressive volume reduction ensued which stabilized at near control volume over a period of 10 min. This regulatory volume decrease (RVD) was attenuated by elevated [K+]o, Ca2(+)-activated K+ channel antagonists, and calmidazolium, a potent calmodulin inhibitor. Inclusion of ATP gamma S in the hypotonic bathing medium led to a loading of stressed axons which resulted in an excessive volume reduction that reflected an overshooting of the RVD response. The latter suggested the importance of phosphorylation/dephosphorylation reactions in the RVD response pathway. Cytochalasin D and colchicine had no effect on the development of the typical RVD response, providing no evidence of involvement of actin or microtubule cytoskeletons in the volume reduction mechanism of the immature axons. The results are consistent with the hypothesis that hypo-osmotic stress activates a calcium/calmodulin dependent membrane pathway, which probably involves transient phosphorylation, leading to a loss of cellular K+ and osmotically obligated water which restorates normal axonal volume. PMID- 2207629 TI - Medullary sites mediating some abdominal vagal reflexes in the ferret using [14C]2-deoxyglucose. AB - The central projections of some abdominal visceral afferents passing through the vagal communicating branch were studied in anesthetized ferrets using [14C]2 deoxyglucose autoradiography. The reflex effects of electrical stimulation of the vagal communicating branch were studied while measurements of jejunal motor activity and transmural potential difference, a marker of electrogenic epithelial transport were made concurrently. The aim of this study was to examine brainstem projections of some afferent fibers in the communicating branch of the thoracic vagus nerve that are necessary for the reflex regulation of small intestinal motor activity and epithelial transport. In urethane-anesthetized ferrets, electrical stimulation of the cut central end of the vagal communicating branch increased jejunal motor activity and electrogenic epithelial transport. In addition, glucose utilization in the left medial sub-nucleus of the nucleus tractus solitarius and the dorsal motor nucleus of the vagus was significantly increased as compared with sham-operated non-stimulated control animals. Identical areas on the contralateral side of the brain showed no change in glucose utilization as compared with sham-operated non-stimulated controls. This functional brain-mapping study strongly suggests that the left medial sub-nucleus of the nucleus tractus solitarius and the dorsal motor nucleus of the vagus, in the ferret, are involved in processing alimentary afferent activity from both the small intestinal musculature and epithelium as well as the reflex changes in efferent vagal nerve activity to the same regions of the alimentary tract. PMID- 2207630 TI - Plasticity in the propagation of hippocampal stimulation-induced activity: a [14C]2-deoxyglucose mapping study. AB - Previous work has suggested that the rewarding effect of hippocampal stimulation develops only as a consequence of neuroplastic change resulting from repeated stimulation experience: naive rats will not initiate self-stimulation for several days, but a prior program of hippocampal kindling greatly facilitates acquisition of self-stimulation. In the current study, the metabolic tracer [14C]2 deoxyglucose was used to measure functional activity during a session of repeated electrical stimulation of the hippocampus to determine whether the resulting activation propagates more widely in experienced hippocampal self-stimulators than in naive rats receiving the same programmed stimulation. A control group of naive unstimulated rats was also included. The results indicated that dorsal CA3 stimulation in naive rats failed to increase metabolic activity in the hippocampus, while in experienced rats, the stimulation produced significant bilateral activation of CA1, CA3, and the ventral subiculum. These results provide support for the hypothesis that development of the rewarding effect of hippocampal stimulation is associated with more widespread propagation of stimulation-induced activity. PMID- 2207632 TI - Laminar profiles of N-methyl-D-aspartate- and quisqualate-induced [Na+]o changes in rat hippocampus. AB - Since plastic changes in neuronal tissue are often associated with changes in responses to excitatory amino acids (EAA), a method is required which permits mapping of functional EAA receptor sites. In this study the measurement of extracellular sodium concentration changes [( Na+]o) induced by iontophoretic application of N-methyl-D-aspartate (NMDA) and quisqualate (Quis) is used as a tool to estimate the density of functional NMDA- and Quis-receptor sites in area CA1 and dentate gyrus of rat hippocampus. Largest decreases of [Na+]o induced by NMDA were found in basal and apical dendritic fields of area CA1 and in stratum moleculare of dentate gyrus at a distance of 50-100 microns from stratum granulare. Peak decreases in [Na+]o induced by Quis occurred at similar positions. Bath application of tetrodotoxin (TTX) suppressed that part of the extracellular Na+ loss mediated by Na+ fluxes through voltage activated Na+ channels. However, the laminar profiles of Quis- and NMDA-induced [Na+]o changes were not affected by TTX. Thus, EAA induced decreases in [Na+]o can be used to detect changes in receptor density and in receptor functionality of hippocampus which had undergone plastic changes. PMID- 2207631 TI - Effects of chronic nicotine on cerebral glucose utilization in the rat. AB - Effects of chronic nicotine on glucose utilization in 45 CNS regions were examined using the 2-deoxy-D-[1-14C]glucose technique in rats. Either L-nicotine (1.0 mg/kg) or saline was injected subcutaneously twice daily for 10 days and once the morning of day 11. On the following afternoon, rats received either nicotine challenge (0.3 mg/kg) or saline subcutaneously 2 min before an intravenous pulse of 2-deoxy-D-[1-14C]glucose. Drug-naive rats given nicotine challenge showed increases of glucose utilization in thalamic nuclei and components of the visual system. Tolerance to nicotine challenge in rats given nicotine chronically was seen in the ventral tegmental area, some components of visual pathways, the cerebellum, and vestibular nuclei; no regions showed sensitization. The percent of rats manifesting most nicotine-induced behaviors either increased (Straub tail, locomotor stimulation, tremors) or did not change (ataxia) over the 10 days of chronic treatment. Plasma from rats given nicotine chronically showed low concentrations of nicotine (12 +/- 1 ng/ml) and higher concentrations of cotinine (124 +/- 6 ng/ml) at the time of assay, with no apparent effect of chronic treatment on nicotine levels after the challenge dose. Changes in regional brain activity, as measured by the 2-deoxy-D-[1-14C]glucose technique, generally do not explain the observed sensitization to nicotine in behavioral assays. PMID- 2207633 TI - Evoked alpha- and mu-rhythm in humans: a neuromagnetic study. AB - We present the results of a neuromagnetic study on the spatial structure of brain rhythms enhanced by photic and somatosensory stimulation, as measured on the occipital, rolandic and frontorolandic regions in humans. It emerges that, while it is always possible to drive the cerebral activity during sustained stimulation at any given frequency, only certain specific frequencies can produce prolonged synchronization (i.e. the oscillating activity elicited by the repetitive stimulation continues well beyond its termination). In both studied modalities we were able to localize equivalent sources for the synchronized responses; their relationship with the known evoked responses is discussed. In the visual modality the synchronization was characterized by a potentiation of the subjects' alpha rhythm. In the somatosensory modality synchronization was reflecting two different activities: one probably related to the rolandic mu-rhythm, the second suggesting the presence of two widely separated and time correlated sources possibly driven by a unique, deep clock. Possible implications for other studies of the dominant brain rhythms, or experimental checks on specific brain models, as well as of the visual and somatosensory evoked responses are discussed. PMID- 2207634 TI - Substantia nigra regulates action of antiepileptic drugs. AB - The cholinergic agonist pilocarpine triggers sustained limbic seizures in rodents. Pilocarpine seizures were blocked by systemic administration of benzodiazepines, barbiturates, valproate and trimethadione, while diphenylhydantoin did not affect, and ethosuximide increased the susceptibility of rats to such seizures. This pattern of action of antiepileptic drugs is characteristic for pilocarpine seizures and different from other rodent models of epilepsy. Although the anatomical substrates in the forebrain involved in the expression of anticonvulsant activity are unknown, the basal ganglia are believed to be essential for the motor expression of pilocarpine seizures. Bilateral microinjections into the substantia nigra, a major output station of the basal ganglia, of midazolam (ED50 38.5 nmol; range 29-52 nmol), phenobarbital (ED50 16 nmol; range 7-39 nmol) and trimethadione (ED50 30 nmol; range 16-56 nmol) protected rats against pilocarpine seizures (380 mg/kg i.p.) Diphenylhydantoin (up to 100 nmol) remained inactive, while ethosuximide (ED50 38 nmol; range 22 65.5 nmol) reduced the threshold for pilocarpine seizures, converting subconvulsant doses of pilocarpine (200 mg/kg i.p.) into convulsant ones. The profiles of action of antiepileptic drugs on pilocarpine seizures were similar following intranigral and systemic administration. These observations suggest that the substantia nigra may mediate some actions of antiepileptic drugs. PMID- 2207635 TI - Second somatosensory cortical area in macaque monkeys. I. Neuronal responses to controlled, punctate indentations of glabrous skin on the hand. AB - Responses of 492 single neurons from the second somatosensory cortical area of macaque monkeys were studied using computer controlled ramp indentations. Results were obtained using chronic recording techniques from lightly tranquilized or awake animals. Amongst those cells that were activated by punctate tactile stimuli, various subclasses of responses were identified that included neurons with phasic and sustained adaptation characteristics. In addition, several cells showed unusual firing patterns, such as delayed responses and reverberating afterdischarges. Latency measurements from 90 cells showed a modal latency to ramp stimuli of 34 ms and a second group of cells whose latency exceeded 75 ms. Measurements of response functions to different velocities of indentation revealed that some cells maintained relatively shallow ascending functions but that most cells were insensitive to the velocity variable. The response characteristics of these neurons in primates are discussed in reference to the hypothesis that in the somatosensory cortex, SII occupies a higher order, serially dependent region in a hierarchy from SI to other parts of the brain. PMID- 2207636 TI - Profound stress-induced alterations in flurazepam's antiseizure efficacy can be attenuated. AB - A new procedure is described for assessing the sensitivity of the benzodiazepine receptor in intact animals. This procedure measures the ability of benzodiazepines to antagonize electrically-induced seizures precipitated by incremental increases in voltage. This functional measure detected stress-induced alterations in benzodiazepine receptor sensitivity, an alteration shown previously with in vitro and in vivo receptor binding techniques. In contrast, mouse rotorod performance, which has been proposed as a behavioral measure of benzodiazepine receptor sensitivity did not show stress-induced alterations. The mechanism of these stress-induced alterations was explored using this incremental electroconvulsive shock procedure (IECS). A 'GABA-negative' benzodiazepine mimicked the effects of swim stress, whereas treatment of animals prior to swim stress with Ro15-1788, a 'GABA-neutral' benzodiazepine, attenuated these stress induced alterations. These data suggest both that these stress effects may be mediated by an endogenous ligand, and that Ro15-1788 may have a novel indication as a prophylactic intervention for individuals at risk for exposure to severe and unusual stress. PMID- 2207637 TI - The selective viability of human foetal brain cells. AB - The influence of various factors upon the survival of human foetal neurones has been examined. The viability of several brain structures was assessed using ethidium bromide and acridine orange fluorescence in both 'intact' and mechanically dispersed tissue. Striatum was least vulnerable to dissociation while cortex, mesencephalon, pons, cerebellum and cord were more vulnerable to a greater or lesser extent. Material can be preserved in vitro with greater viability in the undissociated rather than dissociated state. The effects of other factors including foetal age upon viability are discussed. PMID- 2207638 TI - Effect of basic fibroblast growth factor on neurons cultured from various regions of postnatal rat brain. AB - Neurons from various brain regions of postnatal (15 days after birth) and fetal (16 days gestation) rats were cultured in the presence of basic fibroblast growth factor (bFGF). bFGF increased the survival of neurons from postnatal septum, striatum, midbrain, and hippocampus. Fetal neurons derived from cerebral cortex, septum, striatum, midbrain, thalamus, and colliculus were far more dependent on bFGF for survival in comparison with postnatal neurons. In contrast, cerebellum neurons of postnatal and fetal rat brain did not respond to bFGF. The increase of postnatal and fetal neuronal survival with bFGF treatment (0.01-10 ng/ml) was dose-dependent and reached 2-4-fold and 5-10-fold more than the control, respectively. Fetal cortical neurons showed almost complete dependence on bFGF since almost all neurons died in control cultures. Nerve growth factor was slightly effective only on postnatal septal and striatal neurons, being ineffective on the other neurons tested. These results indicate that bFGF can function as a neurotrophic factor not only on fetal but also on postnatal neurons of the central nervous system, and that bFGF has great potential for application in vivo. PMID- 2207640 TI - Chronic caffeine exposure enhances adenosinergic inhibition of cerebral cortical neurons. AB - Chronic administration of caffeine (s.c. for a period of 14 days in escalating doses of 10-70 mg/kg) increased the sensitivity of rat cerebral cortical neurons to the inhibitory action of microiontophoretically applied adenosine. The sensitivity of spontaneously firing rat cerebral cortical neurons in caffeine treated animals was compared with that of saline-treated controls using the same multiple-barrel micropipettes tested on the same day. Adenosine sensitivity was determined by the I.T50 method. The I.T50 value for 134 neurons in the caffeine treated rats of 130.77 +/- 4.33 (S.E.M.) was significantly (P less than 0.001) different to that of 136 neurons in the saline-treated control rats (222.16 +/- 6.68), indicating a supersensitivity to adenosine in neurons which had been chronically exposed to caffeine. PMID- 2207639 TI - Asymmetric distribution of brain monoamines in left- and right-handed mice. AB - Biogenic amine distributions analyzed in the cerebral neocortex, striatum, anterior hypothalamus, and bulbospinal region, were compared between both hemispheres of left- and right-handed mice. The handedness of mice was determined using a paw preference test. The animals were tested 5 times, once every two weeks, and the biochemical analysis was performed two weeks after the last behavioral evaluation. The results indicated that (1) asymmetrical monoaminergic concentrations exist in the mouse brain. Monoamine contents were found to be higher in the right parietal cortex and anterior hypothalamus than in the left ones; (2) besides the behavioral expression of handedness, left- and right-handed subpopulations of mice differ according to asymmetrical distributions of cortical and bulbospinal NE contents as well as DA turnover of the tuberoinfundibular system. PMID- 2207641 TI - Intraneuronal laminin-like immunoreactivity in the human central nervous system. AB - Because laminin possesses potent neurotrophic activity, laminin-like immunoreactivity was investigated in formalin-fixed human brains, using affinity purified anti-human placental laminin rabbit serum. Distinct laminin-like immunoreactivity was observed in neuronal soma of certain nuclear groups, and a 180-kDa band was noted in an immunoblot study of the supernatant of brain homogenate. These observations imply that many but not all central neurons have laminin-like immunoreactive molecules. Their functional role, however, remains to be clarified. PMID- 2207642 TI - Motoneuronal commands during swimming behaviour in the shore crab. AB - Neurograms of proximal leg motor nerves were obtained during swimming in the shore crab. Whereas excitor motoneurones fire in bursts, the common inhibitor motoneurone discharges tonically with simultaneous spikes in all the motor nerves. The average firing frequency of the common inhibitor increases as the period of the swimming cycle decreases. Moreover, greater fluctuations of the firing frequency of the common inhibitor occurs within long rather than short swim cycle periods. PMID- 2207643 TI - Intermittent stimulation of fusimotor fibres during slow stretch of muscle spindles in the cat. AB - Responses of muscle spindles of the peroneus tertius muscle of the cat were recorded during intermittent fusimotor stimulation, applied during slow stretch, after muscle conditioning by stimulation of the nerve at the test length or at a length 2.5 mm longer. Some static and all dynamic axons evoked afferent bursts whose amplitude was relatively independent of the level of stretch response. Other static axons produced bursts that grew in size with the stretch. PMID- 2207644 TI - Pirenzepine-insensitive muscarinic autoreceptors regulate acetylcholine release in human neocortex. AB - The release of [3H]acetylcholine ([3H]ACh) and its modulation mediated by autoreceptors were investigated in synaptosomes prepared from fresh human cerebral cortex prelabelled with [3H]choline ([3H]Ch) and depolarized in superfusion with 15 mM KCl. The K(+)-evoked release of tritium was almost totally accounted for by unmetabolized [3H]ACh and was largely calcium-dependent. Exogenous ACh decreased the depolarization-evoked release of [3H]ACh in a concentration-dependent manner (EC50 = 1.5 microM). The inhibitory effect of ACh on [3H]ACh release was counteracted by the non-selective muscarinic antagonist atropine. In contrast, the selective M1 receptor antagonist pirenzepine was ineffective. It is concluded that muscarinic autoreceptors regulating the release of ACh are present on cholinergic nerve terminals of human cerebral cortex and appear to belong to a pirenzepine-insensitive subtype. PMID- 2207645 TI - Reversible effects of hypoxia on neurons in mouse dorsal root ganglia in vitro. AB - Mouse dorsal root ganglia (DRG) were isolated and maintained in a tissue chamber. Membrane potential of 'A-type' neurons was recorded with intracellular electrodes. When the supply of oxygen was reduced, cells depolarized by a few mV and then maintained a stable membrane potential or partially repolarized. During depolarization the action potential was reduced in amplitude and the hyperpolarizing afterpotential was depressed. Reoxygenation within 15-88 min was followed by a brief period of hyperpolarization and then complete recovery. In about 60% of the cells, invasion of the cell soma by impulses triggered by dorsal root (DR) stimulation failed during hypoxia while action potentials could still be evoked by stimulation of the peripheral nerve and by direct intracellular stimuli. Conduction from DR into the peripheral nerve stump was unchanged indicating that the blockade of DR-evoked impulse conduction occurred at the bifurcation of the axon. Results with paired pulse stimulation indicated that impulses passing the axon bifurcation leave a long lasting (greater than or equal to 25 ms) post-spike subnormal period. In DRG cells treated with tetraethylammonium (TEA) the calcium-mediated 'shoulder' of the action potential was curtailed during oxygen withdrawal. In contrast to CNS neurons, DRG cells did not show early hypoxic hyperpolarization, nor the delayed hypoxic spreading depression-like depolarization. The findings support the suggestion that the reversible depression of synaptic potentials in the CNS during the early phase of hypoxia is caused by a combination of conduction failure at axon branch points and curtailment of voltage calcium currents of presynaptic terminals, both effects resulting in reduced transmitter output. PMID- 2207646 TI - Cholinergic neurons of the feline pontomesencephalon. I. Essential role in 'Wave A' generation. AB - Wave A in the cat appears to be analogous to P1 in the human. Both are positive middle-latency auditory-evoked potentials, present at slow click rates during wakefulness and REM sleep but absent during slow-wave sleep. Wave A has been recorded in the parabrachial and medial tegmental areas of the midbrain and in thalamic target projections of the reticular activating system. Two nuclei in this system, the pedunculopontine tegmental (PPT) and laterodorsal tegmental (LDT) nuclei, contain cholinergic cells; the cholinergic antagonist scopolamine eliminates Wave A. To test whether PPT and LDT were important in Wave A generation, we attempted to lesion these nuclei bilaterally in 11 cats. Wave A was markedly diminished or absent in all but 2 cats, in which the lesions did not include PPT. Loss of choline acetyltransferase-positive cells in PPT, but not LDT, was correlated with effects on Wave A, i.e. greatest cell loss occurred in cats in which Wave A disappeared, and least cell loss in cats with no change in Wave A. We conclude that the PPT nucleus, and particularly its cholinergic cell component, is essential for Wave A generation and suggests that a similar substrate may be significant for generation of the human P1. PMID- 2207647 TI - Cholinergic neurons of the feline pontomesencephalon. II. Ascending anatomical projections. AB - Immunoreactivity for choline acetyltransferase (ChAT) was analyzed in unoperated cats and in cats in which stereotaxic lesions were made in the pedunculopontine and laterodorsal tegmental nuclei. The fine reaction product revealed moderate to dense ChAT-immunoreactive fiber plexuses throughout the telencephalon, diencephalon, and midbrain. A pontomesencephalic origin of cholinergic innervation to virtually every nucleus of the diencephalon, as well as to various midbrain and basal telencephalic sites was indicated in the cats with lesions, in which the optical density of ChAT-immunoreactivity was significantly decreased as compared to controls. Pontomesencephalic lesions produced no changes, however, in the density of ChAT staining in the cerebral cortex, basolateral amygdala, or caudate nucleus. In addition to ChAT-positive terminal fiber arborizations which were widely distributed, cholinergic fibers-of-passage were traced in the unoperated and operated feline brains. The general course of ChAT fibers cut in cross-section was followed in successive transverse levels, and although pathways originating from the pedunculopontine nucleus demonstrated orientations in every direction, many demonstrated a rostral course. A particularly dense aggregate of ascending ChAT-positive fibers was localized in the dorsolateral sector of the pedunculopontine area which could be followed at more rostral levels into the central tegmental fields and the compact part of the substantia nigra. From the central tegmental fields, numerous ChAT-immunopositive fibers cut in cross section continued to course rostrally in the intralaminar, reticular and lateroposterior nuclei of the thalamus, and a distinct bundle of ChAT fibers coursing dorsolaterally was observed medial to the optic tract ascending to the lateral geniculate. ChAT fibers with dorsolateral orientations were additionally observed in the zona incerta, ventral anterior thalamus, and ansa lenticularis on route to the reticular thalamus, the globus pallidus, and the substantia innominata. Pathways consisting of fibers traced from ChAT-containing cells in the laterodorsal tegmental nucleus could be traced to medial structures such as the periaqueductal gray, ventral tegmental area and dorsal raphe. Medially placed ChAT fibers were additionally followed through the ventral tegmental area, the midline thalamus, and the hypothalamus, up to the medial and lateral septal nuclei. The trajectories of the ascending cholinergic pathways from the pontomesencephalon are discussed in relation to locally generated electrophysiological responses in the cat. PMID- 2207648 TI - Flight and immobility evoked by excitatory amino acid microinjection within distinct parts of the subtentorial midbrain periaqueductal gray of the cat. AB - Unilateral microinjections of the excitatory amino acid, D,L-homocysteic acid (DLH) made in the lateral and ventrolateral parts of the subtentorial (A 1.0-P 1.5) midbrain periaqueductal gray (PAG) of the freely moving cat evoked two distinct patterns of coordinated somatic changes. When DLH injection (80 nmol) was made within the lateral part of the subtentorial PAG it evoked a flight reaction, characterized by strong locomotion (running) and multiple jumps. This flight reaction was quite distinct from the defensive threat display previously described following DLH microinjection in the lateral part of the pretentorial PAG. When DLH injection (80 nmol) was made in the subtentorial PAG region, ventrolateral to the aqueduct, it elicited a cessation of both spontaneous locomotion and general movements (e.g. licking, scratching, grooming, head and limb movements), a reaction termed immobility. The subtentorial PAG regions from which flight and immobility were evoked are seemingly identical to the lateral and ventrolateral subtentorial PAG regions in which hypertensive and hypotensive reactions have been evoked previously by DLH microinjection. The present results together with our previous studies suggest that: (1) the lateral PAG of the cat contains at least two, topographically separable neuronal pools, which mediate different types of defense reactions (i.e. threat display--lateral part of the pretentorial PAG; flight reaction--lateral part of the subtentorial PAG); and (2) excitation of neurons in the ventrolateral PAG alters autonomic and somatic functions, but in a direction opposite to that of lateral PAG neurons, namely decreased somatomotor activity and hypotension. PMID- 2207649 TI - Immunocytochemical localization of the neural-specific regulatory subunit of the type II cyclic AMP-dependent protein kinase to postsynaptic structures in the rat brain. AB - The cellular and subcellular distribution of a major cyclic AMP binding protein in the central nervous system, the neural-specific regulatory subunit of the type II cyclic AMP-dependent protein kinase (RII-B), was analyzed in rat brains with light and electron microscopic immunocytochemical methods. The distribution of the non-neural isoform of the regulatory subunit of the enzyme (RII-H) was also analyzed. It was found that RII-B immunoreactivity was predominantly localized to neurons whereas glial and endothelial cells were unlabeled. In the neurons the RII-B immunoreactivity occurred in the perikaryal cytoplasm and in the dendrites; there was no significant accumulation of immunoreaction product in nuclei, myelinated axons and axon terminals. Although immunoreactivity was never detected in axon terminals, it was characteristically associated with the postsynaptic densities and the surrounding non-synaptic sites in somata, dendrites and dendritic spines. The localization of RII-B antigenic sites did not show specificity to any type of neuron or synapse, but the amount of immunoreactivity varied. The distribution of RII-H immunoreactivity was similar to that of RII-B except that RII-H immunoreaction product was also observed in glial cells and occurred more frequently in myelinated axons. Our data confirm that RII-B is one of the major cyclic AMP binding proteins in neurons, and provide morphological support for the involvement of the type II cyclic AMP-dependent protein kinase in postsynaptic neural functions. PMID- 2207650 TI - Grafting of midbrain neurons into the hippocampus restores serotonergic modulation of hippocampal activity in the rat. AB - The ability of midbrain raphe (MR) cells grafted into serotonin-depleted brain to restore hippocampal responses to synaptically released serotonin was studied using a serotonin-releasing drug, D-fenfluramine (FFA). In normal rats, FFA enhances reactivity of the dentate gyrus (DG) to perforant-path stimulation, while suppressing spontaneous activity. These effects of the drug were dependent on the presence of normal serotonin neurotransmission in the hippocampus. Depletion of brain serotonin markedly attenuated DG reactivity to FFA. MR grafts (4-5 months after transplantation) restored the reactivity of the hippocampus to FFA. Immature MR grafts (3 weeks after transplantation) or septal control grafts could not reproduce the effects of mature grafts. These experiments demonstrate the possible functional incorporation of neural transplants in a host brain and the possible involvement of these grafts in regulation of normal host electrical activity. The combined utilization of a serotonergic graft and a releasing drug (i.e. FFA), in the serotonin-deprived brain, allows the study of serotonin functions in restricted parts of the brain. PMID- 2207651 TI - Differential effects of morphine on histamine metabolism in brain and spinal cord of mice. AB - The effects of morphine on the levels of histamine (HA), its metabolite tele methylhistamine (t-MH) and on t-MH synthesis rates (thought to be indicative of neuronal HA release) were investigated in brain regions and spinal cords of DBA/2J (DBA) and C57/BL6 (C57) mice, two strains known to differ in their sensitivity to morphine. In DBA (a strain highly sensitive to morphine antinociception), morphine (10 mg/kg, s.c.) had no effect on brain regional t-MH or HA levels, but produced a generalized inhibition of regional t-MH synthesis rates ranging from 11 to 53%. The monoamine oxidase (MAO) inhibitor pargyline (used to estimate t-MH synthesis rates) had no effect on HA or t-MH levels in the DBA or C57 spinal cord, indicating the absence of detectable spinal HA turnover. Morphine (10 mg/kg) had no effect on DBA or C57 spinal cord HA or t-MH levels, but significantly increased t-MH synthesis in the DBA but not in the C57 spinal cord. These results suggest that in DBA mice, antinociceptive doses of morphine inhibit HA release in brain, and promote the release of HA from spinal cord. Neither effect was found in C57 mice, which are resistant to morphine antinociception. The relevance of these actions to previous studies showing the blockade of opiate antinociception by H2 antagonists remains to be established. PMID- 2207652 TI - Expression of the neuron-specific glycoprotein GP50 by granule cell cultures. AB - The expression and properties of the neuron-specific glycoprotein, GP50, by neonatal rat granule cells grown in primary tissue culture were studied using the monoclonal antibody MabSM-GP50. GP50 was expressed by granule cells in culture but not by astrocytes or PC12 cells that had been induced to differentiate with nerve growth factor. Immunocytochemical staining of granule cell cultures demonstrated that immunoreactivity was concentrated in the cell body. Although the amount of GP50 increased slowly throughout the culture period the maximum level of expression in vitro was markedly lower than that observed in cerebellum of the comparable age. Radiolabelling of cell surface proteins by lactoperoxidase catalyzed iodination demonstrated that GP50 was expressed on the surface of granule cells. Following phase-partitioning of granule cells in the presence of Triton X-114, 75% of GP50 was found to be present in the detergent phase, indicating that it is an integral membrane protein. Sucrose density gradient centrifugation of Triton X-100 extracts of granule cells resolved GP50 into two components with sedimentation coefficients of 3.6S and 7.3S. The 3.6S species (Mr 42,000 Da) accounted for greater than 80% of the total, indicating that GP50 is present predominantly in a monomeric form within the membrane. These properties are similar to those of GP50 expressed in P12 cerebellum but contrast with the behavior of GP50 from mature brain, in which the 7.3S, hydrophilic form is the predominant species. The results suggest that the mature expression of GP50 may be dependent upon the histotypic pattern of development which occurs in vivo. PMID- 2207653 TI - Inhibition by trypsin of the high-affinity acidic amino acid transport system in C6 glioma cells. AB - The high-affinity uptake of the acidic amino acid D-aspartate was inhibited in a dose- and time-dependent manner, when C6 cells were exposed to trypsin. The protease decreased the maximal velocity for uptake but not its Km, consistent with a reduction in the number of competent carriers at the plasma membrane. Cellular energy production and [K+]i were unaffected, indicating that the transporter itself was the site of trypsin action. Maximum inhibition of uptake was 50%, which suggests the presence of a heterogeneous population of transporters, only half of which is sensitive to trypsin. These results support our earlier postulate that in glial cells, the high-affinity transporter for acidic amino acids is a transmembrane protein, part of which extends into the external environment. PMID- 2207654 TI - Modulation of hippocampal primed burst potentiation by anesthesia. AB - This study demonstrates that the anesthetics urethane and pentobarbital differentially affect a low threshold form of long-lasting synaptic plasticity, termed primed burst (PB) potentiation, in the CA1 area of rat hippocampus. PB potentiation was generated by the delivery of a 5-pulse patterned stimulus train, consisting of one priming pulse followed 170 ms later by a burst of 4 pulses at 200 Hz. PB potentiation could not be reliably generated in urethane-anesthetized rats unless stimulus currents were raised to 150% of baseline levels during the stimulus train. In pentobarbital-anesthetized rats, PB potentiation could always be evoked at baseline stimulus intensities. Differences between the anesthetics which could contribute to their varying effects upon PB potentiation are discussed. PMID- 2207655 TI - Catecholamine reinnervation of supraoptic nucleus after deafferenting mechanical lesions and superior cervical ganglionectomy: histofluorescence and functional assessments in young adult and aged rats. AB - Catecholaminergic innervation of the hypothalamic vasopressin (VP)-secreting supraoptic nucleus (SON) was examined at selected intervals after deafferenting neurosurgical lesions, with respect to potential contribution of peripheral vascular sympathetic fibers. Young adult (3 months) and aged (20 months) male F344 rats were subjected to mechanical knife-cut lesion just caudal and medial to the SON, superior cervical ganglionectomy (SCGx), or both surgeries. SON and lesion sites were assessed at 4, 14, 30 or 45 days after surgery, by CA histofluorescence. Functional evaluation in rats subjected to chronic lesions consisted of monitoring water balance (water consumption and urine volumes, and urine osmolality and VP content) in individual rats for presurgical and postsurgical intervals. Histofluorescence evaluation showed that SCGx did not affect the overall SON fluorescence pattern, although a minor sympathetic contribution to that pattern was discerned by comparing SON in rats subjected to lesion alone vs SCGx + lesion. Morphological reinnervation of SON was accomplished at 30 days in young rats, and 45 days in aged rats, after both lesion and SCGx. In young rats, histofluorescence density 30 days after deafferentation was denser than the innervation pattern seen in intact (sham lesioned) animals, while reinnervation at 45 days postsurgically in aged rats only approximated the presurgical pattern. Vasopressin excretion and corresponding water conservation measures were compromised by SON deafferentation at both ages; excreted VP levels and water balance did not rebound to presurgical values at chronic postsurgical intervals in either young or aged rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2207656 TI - Spinal dorsal horn neurons in elevated extracellular calcium: cell properties and spontaneous discharges. AB - Recordings were made from neurons in the dorsal horn (DH), and from dorsal and ventral roots (DRs and VRs) of isolated spinal cords of infant mice. Raising calcium concentration ([Ca2+]) in the organ bath from 1.2 to 2.4 mmol/l resulted in a slight hyperpolarization, elevation of threshold current (rheobase), and augmentation of excitatory postsynaptic potentials (EPSPs). In many cells EPSPs acquired a much prolonged late phase. Orthodromic stimulation evoked in some DH neurons an action potential that had the same threshold as, and coincided in time with, the 'dorsal horn response' (DHR) recorded from DR. In spinal cords bathed in elevated [Ca2+], DR recordings showed irregularly recurring spontaneous waves, and DH neurons generated spontaneous EPSPs, often with spikes. Some neurons fired irregularly timed spontaneous action potentials that did not appear triggered by EPSPs. In less than 50% of the neurons the spontaneous EPSPs coincided in time with the spontaneous DR waves. The action potentials that appeared without EPSP were fired independently from DR activity. These observations confirm that elevation of interstitial free calcium concentration results in strong enhancement of excitatory transmission, especially of an EPSP of much extended duration. Virtually all neurons showed increased spontaneous activity in high [Ca2+], but only a minority appeared recruited into the synchronized discharges that are detectable as spontaneous waves in DR and VR recordings. PMID- 2207657 TI - Behavioural modification of bulbospinal serotonergic inhibition and morphine analgesia. AB - Habituation to the stress of sham nociceptive testing enhances a rat's sensitivity to noxious thermal stimuli and reduces the antinociceptive effect of a subsequent acute dose of morphine. Since serotonin (5-hydroxytryptamine, 5-HT) mediates stress responses, experiments were designed to elucidate the role of 5 HT in these phenomena. Intrathecal methysergide or 5,7-dihydroxytryptamine (5,7 DHT) reduced baseline tail-flick latencies of novice rats to those of habituated animals. Morphine dose-response relationships were fitted to a 4 parameter sigmoidal function. Baseline latencies of novice animals were increased by 5 hydroxytryptophan (5-HTP) and reduced by parachlorophenylalanine (PCPA) in both reflex tests and in the hot-plate test, but latencies of habituated animals were unchanged by either treatment. In both reflex tests, the maximum effect due to morphine was increased by 5-HTP and reduced by PCPA in novice but not in habituated animals. We conclude that the serotonergic component of morphine's bulbospinal action represents the stress of the testing environment rather than an essential part of morphine's action. PMID- 2207658 TI - Phorbol esters increase insulin binding in astrocytic glial but not neuronal cells in primary culture from the brain. AB - In this study we used differential culturing techniques to study the effects of phorbol esters on insulin receptors on neuronal and astrocytic glial cells in primary culture from the brain. 12-O-Tetradecanoyl-phorbol-13-acetate (TPA), a potent activator of protein kinase C (PKC), increased [125I]insulin binding in a time- and concentration-dependent manner with a maximally effective dose of 50 nM TPA for 2 h in glial cells. Treatment with TPA did not affect [125I]insulin binding in neuronal cells. The TPA effect on glial [125I]insulin binding was specific as evidenced by the observation that potencies of phorbol ester analogs to increase [125I]insulin binding were similar to their abilities to stimulate PKC. Competitive-inhibition experiments indicated that this effect of TPA was due primarily to an increase in the number of high affinity insulin binding sites on glial cells. Removal of the TPA after pretreatment resulted in a recovery from its effects within 6 h. The increase in glial insulin binding was not accompanied by an increase in insulin-sensitive glucose uptake, suggesting that TPA inactivates the glial cell receptors as it increases their numbers. PMID- 2207659 TI - Mapping of serotonin-like immunoreactivity in the ventral nerve cord of crayfish. AB - Whole-mount immunohistochemical technique using antibody to serotonin (5-HT) had been used to map presumptive serotoninergic structures in the ventral abdominal and thoracic nerve cord of crayfish Procambarus clarkii. 5-HT immunoreactivity was detected in more than 30 cell bodies, numerous fibers and peripheral nerve endings of root plexus and neuropilar regions. Immunoreactive fibers are arranged in 3 pairs of rostrocaudal bundles. The median (MFB) and the lateral fiber bundles run longitudinally through the entire thoracic and abdominal nerve cord (first thoracic T1 to sixth abdominal A6 ganglia). The central (CFB) fiber bundles extend only from the subesophageal to the fourth thoracic ganglia. In the 4 anterior thoracic ganglia (T1-T4), two lateroposterior cell bodies send their major processes in the ipsilateral MFB. In the fifth thoracic (T5) and first abdominal (A1) ganglia, the pattern of reactive structures is similar. Two large anterior cells which send a single prominent process to join the ipsilateral MFB and 4 smaller posterior cells. In other abdominal ventral ganglia, immunoreactive structures are smaller and less labeled. Cell bodies are displayed in two kinds of arrangement giving the appearance of two distinct homogeneous groups of ganglia: an anterior group (A2-A3-A4) that contained two pairs of small neurons and a posterior group (A5-A6) that contained only a large unpaired medial neuron. These results were discussed in relation to the serotonin-like immunoreactivity pattern previously described in lobster by Beltz and Krawitz. PMID- 2207660 TI - A subset of progesterone target neurons have axonal projections to the midbrain. AB - Progestin-concentrating neurons in the preoptic area and hypothalamus that project to the midbrain in the female rat were identified using the combined steroid hormone autoradiography-retrograde axonal tracing technique. Progesterone target neurons were most abundant in the periventricular preoptic area and the medial preoptic nucleus, and in the ventromedial and arcuate nuclei of the hypothalamus. In the medial preoptic area as a whole, about 14% of the progestin concentrating cells were afferent to the midbrain. More specifically, 23% of medial preoptic nucleus progesterone target neurons communicated directly with midbrain cell groups, whereas a much smaller percentage (2%) of periventricular preoptic target neurons projected to the midbrain. In the medial basal hypothalamus as a whole, 11% of the progestin-concentrating cells detected sent axons to the midbrain. This proportion was slightly higher in the ventromedial nucleus (15%), and much lower in the arcuate nucleus (3%). In the dorsal and lateral hypothalamic areas, close to 30% of the progesterone target neurons sent axons to the midbrain, although the total number and density of target cells in the two latter areas was low. These data support the idea that transduction by forebrain target neurons of the progesterone signal into altered synaptic transmission in the midbrain is one route through which progesterone can influence a variety of behaviors. PMID- 2207661 TI - Methylmercury uptake in rat primary astrocyte cultures: the role of the neutral amino acid transport system. AB - The significance of the dense labeling pattern of methylmercury (MeHg) over astrocytes in areas of damaged cortex remains obscure, and the extent to which individual neurons are altered by MeHg accumulation in astrocytes is unknown. As a first step in understanding the relationship between the astrocyte and the mechanisms of MeHg's neurotoxicity, studies were directed at how MeHg is transported into cultured astrocytes. Uptake of [203Hg]MeHg in primary astrocyte cultures from neonatal rat cerebral cortex following incubations with MeHgCl conformed to a simple diffusion process. Uptake of [203Hg]MeHg by astrocytes exhibited the kinetic criteria of a specific transport system when added to the media as the L-cysteine conjugate. Saturation kinetics, substrate specificity and inhibition, and trans-stimulation were demonstrated in the presence of this SH containing amino acid. Cysteine-mediated uptake of MeHg was inhibited by the coadministration of L-methionine, and 2-aminobicyclo-[2,2,1]-heptane-2-carboxylic acid. 2-Methylaminoisobutyric acid was ineffective in inhibiting the uptake of the MeHg-cysteine conjugate. Preloading of the astrocytes with glutamate was moderately effective in trans-stimulating the uptake of MeHg-cysteine conjugates, while in the absence of cysteine, uptake of [203Hg]MeHg was unchanged. These results indicate the presence in astrocytes of a neutral amino acid carrier transport System L, capable of selectively mediating cysteine-MeHg uptake. The substrate specificity and high affinity of this transport system resemble the properties of the System L neutral amino acid transport across the blood-brain barrier in the rat. Cellular uptake of MeHg-cysteine conjugates was not inhibited by preincubation of astrocytes with 100 microM N-ethylmaleimide or NaF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2207662 TI - Regulated release of multiple peptides from the bag cell neurons of Aplysia californica. AB - The bag cell neurons of Aplysia californica synthesize and store large amounts of peptides derived from the egg-laying-hormone (ELH) neuropeptide precursor. Different sets of peptides derived from the amino- and carboxyl-terminal regions of the prohormone possess unique biological activities, and are packaged in distinct sets of secretory granules. We report here quantitative measurements of the amounts of the peptide products stored in and released from the bag cell neurons using high pressure liquid chromatography (HPLC) and amino acid composition analysis. These studies demonstrate that both the autocrine acting bag cell peptides (BCPs) and ELH are released coincident with electrical activity in the bag cell cluster. The composition of the released peptide mixture is similar to that stored in the bag cells. ELH and other carboxy-terminal derived peptides are most often present at 5-fold greater levels than the BCPs. These results provide further insight into the use of multiple chemical messengers by the bag cell neurons. PMID- 2207663 TI - Some enkephalinergic pathways in the brain of Rana esculenta: an experimental analysis. AB - The distribution of proenkephalin-like immunoreactivity in the brain of Rana esculenta was examined after either unilateral transection of the lateral forebrain bundle or unilateral ablation of the optic tectum. Following transection of the lateral forebrain bundle, proenkephalin-like immunoreactivity could no longer be detected on the ipsilateral side of the brain in either the pretectal area or the nuclei of the mesencephalic tegmentum which receive projections from the ipsilateral lateral forebrain bundle. Following ablation of the optic tectum, proenkephalin-like immunoreactivity could no longer be detected in the area of the ipsilateral isthmic nucleus which receives projections from the ipsilateral optic tectum. These results suggest that both enkephalinergic projection neurons and enkephalinergic local-circuit neurons regulate visual information processing in the frog. It is proposed that the descending telencephalic enkephalinergic pathway regulates avoidance and prey-catching behavior in the frog. The role(s) of the enkephalinergic tecto-isthmic pathway in the visual behavior of the frog remain(s) to be determined. PMID- 2207664 TI - Increased efflux of a haemoglobin-like protein and an 80 kDa protease into push pull perfusates following the induction of long-term potentiation in the dentate gyrus. AB - In a previous communication, we reported an increase in protein efflux into perfusates obtained from push-pull cannulation of the dentate gyrus, following induction of long-term potentiation (LTP) in the perforant path. LTP was accompanied by a delayed but general increase in protein efflux. Protein B5 (MW 14 kDa), because of its relatively high concentration in the perfusates and absence from serum, has been chosen for further characterization. Spectrophotometric analysis, in situ proteolysis, two-dimensional electrophoresis and immunoblotting, revealed that protein B5 is indistinguishable from haemoglobin. A persistent increase in an 80 kDa protease, detected by SDS-PAGE zymography, was also seen after the induction of LTP. We consider the possibility that the increased haemoglobin content of perfusates after the induction of LTP may reflect an LTP-associated increase in the release (or activation) of proteases into extracellular space, leading to proteolytic breakdown of blood clots in the vicinity of the cannula. Evidence in favour of this hypothesis is provided. PMID- 2207665 TI - Variation in the pattern of [Ca2+]i change induced by acetylcholine in cultured hippocampal neurons. AB - Acetylcholine (ACh) caused various patterns of change in the intracellular Ca2+ concentration ([Ca2+]i) in cultured rat hippocampal neurons. We studied the underlying mechanisms of the [Ca2+]i changes with simultaneous recording of [Ca2+]i and membrane potential/current. In most cases, [Ca2+]i rise was accompanied by a membrane depolarization. The [Ca2+]i change was significantly reduced when the membrane was voltage clamped, which implies that most of the [Ca2+]i rise results from the Ca2+ influx through the voltage-gated Ca2+ channel activated by the membrane depolarization. The membrane depolarizations were classified into two types, one associated with membrane conductance decrease and the other associated with membrane conductance increase. The former results from potassium conductance ((gK+) decrease, and the latter may result from the activation of a Na(+)-permeable channel. However, [Ca2+]i elevation was also observed in some neurons showing membrane hyperpolarization in response to ACh. This seems to show that ACh liberates Ca2+ from the intracellular Ca2+ store, resulting in the activation of a calcium-dependent K+ channel (KCa). The variations of ACh response in the hippocampal neurons seem to result from a variety of muscarinic acetylcholine receptors and various species of ion channels governed by those receptors. PMID- 2207666 TI - Gating of somatosensory input by human prefrontal cortex. AB - Somatosensory evoked potentials (SEPs) to median nerve stimulation were recorded in controls and in patients with focal lesions in dorsolateral prefrontal cortex (PFCx). Unilateral PFCx lesions increased the amplitude of the P26 component generated in postcentral areas 1 and 2. The amplitudes of the N28, P45 and N67 SEP components recorded over post-rolandic and frontal electrodes were also enhanced by PFCx damage. In contrast, the N19 component generated in postcentral area 3b was unaffected by PFCx lesions. The results indicate that PFCx exerts inhibitory modulation on sensory processing that may be mediated by corticocortical PFCx-parietal connections. PMID- 2207667 TI - Analysis of facial cold receptor activity in the rat. AB - Afferent activity of single facial cold receptors was extracellularly recorded from infraorbital nerve fibers in the rat, and the response properties of 28 receptors to thermal stimulation were quantitatively studied. Generally, on repeated stimulation, the afferent activity was highly reproducible and was not dependent on previous adapting temperatures. At constant temperatures, a periodic pattern was apparent in the discharges of 24 receptors; in the remaining 4 receptors periodic elements could not reliably be detected. The temperature dependence of the cyclic pattern corresponded to that observed in other mammalian cold receptor populations: we observed regular impulse groups (bursts) at lower and beating activity at higher adapting temperatures. Rapid changes of temperature induced transient alterations of activity. The dynamic response to cooling was biphasic, indicating a complex sequence of receptor events. A transient acceleration of impulse frequency was followed by a dynamic burst discharge which was characterized by longer pauses and a greater number of impulses per burst compared with the steady-state activity at the same temperature. This indicates a deceleration of the periodic receptor events during the adaptation process following dynamic responses, which is accompanied by a concomitant shift of these processes to a more pronounced suprathreshold condition. In an additional series of experiments, parameters of the periodic activity in the rat were compared with corresponding data of facial and lingual cold receptors in the cat. Whereas the number of impulses per cycle was similar in the 3 receptor populations, the frequency of the periodic pattern proved to be considerably higher in the rat than in the cat. PMID- 2207669 TI - Comparative study of esterases in brains of the vertebrates. AB - Disc gel electrophoretic patterns of esterases obtained in the buffer (0.1 M Tris HCl buffer pH 7.4) extracts of the brains of twelve species belonging to various classes of vertebrates ranging from fishes to mammals are compared. Substrate specificity and inhibitor sensitivity is used to classify the enzymes into different classes of esterases. The pattern obtained does not suggest distribution of any specific enzymes to a particular class of vertebrates nor does it suggest any evolutionary change from fish to mammals. Some fast moving bands are observed in fishes and amphibians. Esterases with active thiol groups (Aryl and Esdp esterases) exhibit wide distribution among the species studied. The enzymes which are resistant to inhibition by eserine, pCMB and DFP (Acetyl and ER esterases) are present in the tetrapods studied. PMID- 2207668 TI - Binocularity in the lateral geniculate nucleus of the alert macaque. AB - We examined the timing and the laminar distribution of binocular interactions and non-dominant eye effects in the lateral geniculate nucleus (LGN) of the alert macaque. Flash-evoked multiunit activity (MUA) was recorded simultaneously from multiple LGN laminae during contralateral eye, ipsilateral eye and binocular stimulation. Evidence of binocularity was noted in all laminae except 4. Inhibitory effects included (1) binocular suppression, a 15-70% reduction in the peak amplitude of MUA during binocular, compared to monocular stimulation of the dominant eye for that lamina, and (2) non-dominant suppression, a 10-45% reduction in MUA below its spontaneous level, with stimulation of the non dominant eye. In lamina 3, the onset of this effect often preceded that of the excitatory response to stimulation of the dominant eye, and was coincident with non-dominant suppression in lamina 2, and with the dominant eye-mediated excitatory response in contralaterally innervated lamina 1. This is consistent with a parvo/magnocellular interaction. Corresponding excitatory effects, binocular and non-dominant facilitation, were also noted throughout LGN. The latter occurred both within the time frame of retinally driven activity (15-65 ms), and at longer latencies as well. The earliest response in lamina 6 of striate cortex, the origin of the corticogeniculate projections, was 30-35 ms, thus precluding a role of corticofugal modulation in the earlier effects in LGN. PMID- 2207670 TI - Anesthesia influences the outcome from experimental spinal cord injury. AB - The effect of anesthesia upon the functional outcome after experimental spinal cord injury (SCI) was studied in 221 rats subjected to graded weight drop contusion in the thoracic cord. Neurologic function was assessed in a blinded fashion for one week after injury using a modification of the method of Tarlov. The post-mortem concentrations of serotonin and its metabolite were measured in injured and surrounding spinal tissues in a subset of animals in order to estimate the survival of descending long-tract axons. In initial studies using non-ventilated animals where body temperature was not controlled (n = 130), halothane anesthesia was associated with significantly better neurologic scores at all levels of injury (50, 100 and 250 g.cm) in comparison to pentobarbital. In a second experiment under these conditions (n = 53) the effect of halothane was observed after a 50 g.cm injury in comparison to both pentobarbital and nitrous oxide. Improved neurologic recovery was accompanied by the preservation of normal serotonin and metabolite concentrations in spinal tissue caudal to the site of injury. These values did not differ from those measured in sham-operated animals. Separate experiments (n = 12) revealed halothane's preservation of somatosensory evoked responses during the early postinjury period in animals showing improved neurologic recovery. Subsequent experiments (n = 12) were performed to assess the effect of oxygen supplementation and the control of rectal temperature and a separate series of acute experiments (n = 14) examined arterial blood pressure responses to injury in halothane- and pentobarbital-anesthetized animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2207671 TI - Uncoupling of cerebral blood flow and glucose metabolism in conscious rats with chronic renal hypertension. AB - In an analysis of 46 individual brain structures and regions, we found that 12-14 weeks of renal hypertension in rats were associated with a 42% increase in cerebrovascular resistance, an average 28% reduction in cerebral blood flow, and no general change in cerebral glucose metabolism. A specific increase in metabolic activity, however, was identified in locus coeruleus. Generalized cerebral vasoconstriction resulting from central noradrenergic innervation originating in locus coeruleus is a possible explanation for the uncoupling of cerebral blood flow and metabolism in rats with chronic renal hypertension. PMID- 2207672 TI - Transient increase in vimentin in axonal cytoskeletons during differentiation in NB2a/d1 cells. AB - The localization of vimentin (Vm) within the Triton-insoluble cytoskeleton was characterized during differentiation of mouse NB2a/dl neuroblastoma cells. Vm staining increased within neurites during the first day of differentiation, and then rapidly declined in both perikarya and neurites. By contrast, immunoreactivity against extensively phosphorylated forms of the high molecular weight neurofilament subunit (NF-H) was absent until the third day after differentiation. Immunoblot analyses confirmed that these alterations reflected specific changes in Vm and NF-H steady-state levels. Metabolic labeling demonstrated a decrease in the rate of Vm synthesis by the third day of differentiation. We conclude that changes in incorporation of intermediate filament species into the axonal cytoskeleton reflect distinct stages in neurite outgrowth and maturation; i.e., the Vm filament system may participate in initial stages of neuritogenesis during which outgrowth is most rapid, while NFPs may subsequently function in the establishment of a stabilized axonal cytoskeleton. PMID- 2207673 TI - Differential induction of class I and II MHC antigen expression by degenerating myelinated and unmyelinated axons. PMID- 2207674 TI - Botzinger expiratory neurons may inhibit phrenic motoneurons and medullary inspiratory neurons during vomiting. AB - During vomiting, phrenic motoneurons exhibit bursts of vigorous discharge while bulbospinal inspiratory neurons are mostly silent. To determine how this activity pattern correlates with the behavior of Botzinger (BOT) expiratory (E) neurons, which inhibit both phrenic motoneurons and medullary inspiratory neurons, we recorded from 20 augmenting BOT E neurons in decerebrate, paralyzed cats. During fictive vomiting, all BOT E neurons fired between bursts of phrenic discharge and thus could contribute to the concurrent lack of firing of phrenic motoneurons. PMID- 2207675 TI - The early decay of long-term potentiation in the hippocampal CA1 region in vitro is reduced by activators of protein kinase C. AB - The effect of the exogenous protein kinase C (PKC) activator phorbol-12,13 diacetate (PDAc) on the early (0-10 min) time course of long-term potentiation (LTP) has been studied in the CA1 region of the guinea pig hippocampal slice. As shown previously, following a brief tetanus LTP develops almost linearly towards a peak value within 20-25 s, and decays thereafter rapidly to about a third of the peak value within 10 min after tetanization before a more stable level is reached. In the presence of 1.0 microM PDAc the growth phase of LTP is prolonged to 40-50 s, and the subsequent early decay is reduced. This reduction of the early decay resembles that previously found when increasing the number of afferent impulses of the LTP-generating tetanus. Examination of the early time course in solutions with different calcium-magnesium concentration ratios suggests that the observed effect of PDAc is not directly mediated via a change in presynaptic release probability, another effect observed after phorbol ester application. The results show that PKC activity is involved in the early stage of LTP development and support the idea that the early phase of LTP represents the same modification process as that underlying the more sustained phase of LTP. PMID- 2207676 TI - Developmental changes in blood-nerve transfer of albumin and endoneurial albumin content in rat sciatic nerve. AB - The rate of entry of albumin into the endoneurial space and its content within that compartment during development were investigated by measuring the permeability coefficient-surface area product to 125I-albumin (PSA) of the blood nerve interface (BNI), endoneurial residual plasma volume (Vp), blood-nerve interface index to albumin, and endoneurial water content in sciatic nerves of rats ranging in age from 1 to 24 weeks. There was a 30-fold reduction in PSA and a 4-fold decrease in Vp from 2 to 24 weeks, indicating that the endoneurial capillaries and perineurium become less permeable during development. On the other hand, the Alb-BNI index was relatively small at 1 week, increased to a peak value around 6-8 weeks, and then decreased to adult values by 13 weeks. The smaller Alb-BNI index in the neonatal period is consistent with endoneurial albumin being cleared across a permeable perineurium by epineurial lymphatics. Subsequently, as the perineurium becomes less permeable, endoneurial albumin content increases. It then decreases as the endoneurial capillary permeability also decreases. Additionally, metabolic clearance of albumin, especially during the first 2-3 weeks, by axons and glia to meet the nutritive requirements of rapid axonal growth and myelination could be partly responsible for a lower Alb BNI index. It is suggested that in the developing nerve, the combination of epineurial lymphatics and a relatively permeable perineurium, together with axonal and glial uptake and protein catabolism aid in the clearance of plasma derived osmolytes from the endoneurial space, and thus prevent the elevation of endoneurial hydrostatic pressure and onset of oedema that would have been seen in an adult nerve with a comparably permeable BNI. PMID- 2207678 TI - The effect of antimitotic agents on the intraneuronal distribution of lysosomes. AB - We previously showed that a single injection of colchicine into the lateral cerebral ventricle of the rat causes a redistribution of lysosomes from their normal localization in neuronal cell bodies into dendrites. In the present report we have examined the time course and specificity of this effect using a variety of microtubule poisons. Dipeptidylaminopeptidase II (Dpp II), a lysosomal marker enzyme, histochemistry was used to visualize lysosomes at the light microscopic level. Acid phosphatase, another lysosomal enzyme, histochemistry was used to confirm the Dpp II localization of lysosomes. Two h after an intracerebroventricular (i.c.v.) injection of colchicine, the distribution of neuronal lysosomes was drastically altered. Lysosomes in a number of neuronal populations were observed to move from the soma to the dendrites. This effect was maximal between 12 and 24 h and was partially reversed by 96 h. Injections of colcemid or podophyllotoxin, drugs that bind to tubulin rapidly, and much less tightly than colchicine, produced a much less pronounced alteration in the intraneuronal distribution of lysosomes. Injections of vinblastine or vincristine, whose binding kinetics range between that of colchicine and that of colcemid and podophyllotoxin, resulted in a redistribution of lysosomes which was less pronounced than the effects of colchicine but more pronounced than that caused by colcemid and podophyllotoxin. Likewise, treatment with other related compounds, 2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone (A-C compound) and lumicolchicine, whose binding to tubulin is extremely rapid and reversible or non existent, produced little or no alteration in the intraneuronal distribution of lysosomes. The results suggest that lysosome redistribution may be dependent upon a relatively slow dissociation rate constant of these drugs from tubulin, and this transport may occur when normal microtubule function is compromised. PMID- 2207677 TI - Redistribution of neuronal lysosomes induced by colchicine: an electron microscopic quantitative study. AB - We have previously demonstrated that a single injection of the microtubule poison colchicine, into the lateral cerebral ventricle of the rat, induced a rapid redistribution of the lysosomal marker enzymes, dipeptidylaminopeptidase II (Dpp II) and acid phosphatase, from their normal location in neuronal cell bodies out into the dendrites. In the present study, we have quantitatively analyzed this phenomenon at the electron microscopic level by identifying and counting the number of lysosomes and mitochondria in neuronal cell bodies and dendrites of control and colchicine-treated rats. Areas examined included the anterior dorsal (AD) thalamus, pontine nucleus, and facial nucleus. The results show that the cytoplasm of these neurons contains significantly fewer large lysosomes after treatment with colchicine while the dendrites become abnormally enriched with large and small lysosomes after treatment. Lysosomes were rarely seen in the axons of either control or colchicine-treated animals. A significant increase in the density and the shape of mitochondria was also observed in the dendrites following colchicine treatment. The data presented support the hypothesis that neurons contain a transport system which selectively translocates lysosomes, and possibly other organelles, into dendrites. The size, shape, and number of these organelles may change as a result of this transport. PMID- 2207679 TI - Localization of serotonin immunoreactivity in cephalopod visual system. AB - The distribution of 5-HT-like immunoreactivity in paraformaldehyde-fixed sections of retina, optic nerve and the optic lobe of Octopus vulgaris was studied by both immunofluorescence and avidin-biotin complex (ABC) immunohistochemical methods utilizing polyclonal antibodies to 5-HT. Some immunoreactive serotonin-containing cells were demonstrated in the retinal plexus, optic nerve, the ciliary body and the lens-generating tissue by both methods. An analysis of dissected retina and optic nerve of Octopus vulgaris by high pressure liquid chromatography (HPLC) with an electrochemical detector (ECD) also showed the presence of 5-HT. In the optic lobe, three 5-HT-immunoreactive bands in the plexiform layer of the cortex were clearly immunostained, and in the medulla both the cell islands and the neuropil contained some cells immunostained by both fluorescein isothiocyanate (FITC) and ABC methods. This is the first report on the systemic immunocytochemical visualization of 5-HT-containing cells and/or fibers in the cephalopod visual system. PMID- 2207680 TI - Reflex effects on gamma fusimotor neurones of chemically induced discharges in small-diameter muscle afferents in decerebrate cats. AB - The effects on fusimotor discharge rate of algesic agents (bradykinin, potassium chloride, histamine, 5-hydroxytryptamine) and lactic acid, applied by close arterial injection into triceps surae muscles, were investigated in decerebrate cats. Fusimotor discharge was recorded from filaments dissected free from otherwise intact nerves to the triceps muscles. The substances applied induced an increase in discharge rate of spontaneously active gamma fusimotor neurones as well as a recruitment of previously silent ones. Skeletomotor discharges and/or muscle tension changes occurred only occasionally. The increase in fusimotor discharge rate was not always completely abolished by severing the nerves to triceps. What remained was a short-lasting burst at the very onset of blood pressure fall. It was concluded that the increase in fusimotor discharge rate was mainly, but not solely, elicited reflexly by discharges from Group III and/or IV muscle afferents sensitive to algesic agents. An elevated fusimotor activity might be expected to accompany muscle inflammation and/or trauma when these agents are liberated in muscle tissue. The increase in fusimotor discharge rate elicited by lactic acid injections indicates that the fusimotor system might also be involved in neural processes of muscular fatigue. PMID- 2207681 TI - Properties of nociceptive and non-nociceptive neurons in trigeminal subnucleus oralis of the rat. AB - Recent studies have provided evidence suggesting the involvement of rostral components of the V brainstem complex such as trigeminal (V) subnucleus oralis in orofacial pain mechanisms. Since there has been no detailed investigation of the possible existence of nociceptive oralis neurons in the rat to substantiate this recent evidence, the present study was initiated to determine if neurons responsive to noxious orofacial stimuli were present in subnucleus oralis and to characterize their functional properties. In anesthetized rats, recordings were made of the extracellular activity of single neurons functionally characterized as low-threshold mechanoreceptive (LTM), wide dynamic range (WDR) or nociceptive specific (NS) neurons. The 342 LTM neurons responded only to light mechanical stimulation of orofacial tissues. The mechanoreceptive field of the LTM neurons included the intraoral region in 28% and was localized to the adjacent perioral area in 65%. For 95% the field was localized within one V division. Responses evoked in LTM neurons by electrical stimulation of the orofacial mechanoreceptive field revealed A fiber afferent inputs but no activity that could be attributed to C fiber afferent inputs. The 72 nociceptive neurons included 52 WDR neurons which responded to light (e.g. tactile) as well as noxious (e.g. heavy pressure; pinch) mechanical stimulation of perioral cutaneous and intraoral structures, and 20 NS neurons which responded exclusively to noxious mechanical stimuli. They also differed from the LTM neurons in that 36% of the WDR and 20% of the NS neurons had a mechanoreceptive field involving more than one V division. However, in accordance with our findings for the LTM neurons, the majority of WDR and NS neurons had a mechanoreceptive field involving the intraoral and perioral representations of the mandibular and/or maxillary divisions; those neurons having a mandibular field which especially included intraoral structures predominated in the dorsomedial zone of subnucleus oralis whereas those with a perioral mechanoreceptive field which particularly involved the maxillary division were concentrated in the ventrolateral zone of oralis. In contrast to the LTM neurons, 57% of the WDR and 67% of the NS neurons showed evidence of electrically evoked C fiber as well as A fiber afferent inputs from their mechanoreceptive field. We also noted suppression of the electrically evoked responses by heating of the tail or pinching of the paw. This effect was considered to be a reflection of diffuse noxious inhibitory controls, and was seen in NS as well as WDR neurons; most, but not all, of these neurons received A fiber as well as C fiber orofacial afferent inputs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2207683 TI - Contrasting effects of urethane and pentobarbitone anaesthesia on the electrical properties of rat jaw-elevator motoneurones. AB - Our main finding is that elevator motoneurones do not show sustained firing to intracellular injections of depolarising current pulses in rats anaesthetised with urethane. In contrast, virtually all elevator motoneurones show sustained firing in pentobarbitone-anaesthetised rats. The differences in firing are not associated with significant differences in membrane potential, spike amplitudes, AHP amplitude or duration, input resistance, time constant or rheobase (P greater than 0.06 in all cases). However, there are clear differences in the extent of sag seen under the two anaesthetics and so we tentatively suggest that the anaesthetics may differ in their effects on the inward rectifier. PMID- 2207682 TI - Release of acetylcholine, gamma-aminobutyrate, dopamine and glutamate, and activity of some related enzymes, in rat gustatory neocortex. AB - The gustatory neocortex (GN), final relay along the gustatory pathway, is a region of the brain involved in the neural integration of feeding behavior. Since information on the neurotransmitters in this nucleus is scarce, the aim of the present work was to establish whether acetylcholine (ACh), gamma-aminobutyric acid (GABA), dopamine and glutamate may act as transmitters within this structure. It was found that GN slices are able to release labeled GABA, ACh and glutamate but not dopamine. Additionally, it was possible to detect significant glutamic acid decarboxylase, choline acetyltransferase and acetylcholinesterase activities in GN homogenates. The activity of the two enzymes involved in acetylcholine metabolism was higher than that observed in other cortical regions. These findings suggest that GABA, ACh and glutamate probably are neurotransmitters in the GN, whereas dopamine is not. PMID- 2207685 TI - The cholinergic system in retinal transplants in rats. AB - Retinas from embryonic day 13 or 14 Sprague-Dawley albino rats were transplanted to the brainstem of newborn rats with unilateral eye enucleation at birth. Two months after the transplantation, the activity and distribution of acetylcholinesterase and choline acetyltransferase were studied using histochemical and immunocytochemical methods respectively. Results obtained showed that the staining patterns of these two cholinergic enzymes in the retinal transplants were essentially the same as those observed in the retinas of normal rats and in the control retinas of the recipient animals. The similarities in the distribution of these two cholinergic enzymes in these retinas suggest that the cholinergic system in the retinal transplants is likely to be functional. PMID- 2207684 TI - Subarachnoid spinal cord transplantation of adrenal medulla suppresses chronic neuropathic pain behavior in rats. AB - Several weeks after transection of the sciatic and saphenous nerves, rats respond by self-injury of the denervated limb ('autotomy'). This behavior serves as a model of neuropathic pain. In this study we allografted fragments of rat adrenal medulla into the subarachnoid space of other rats, at lumbar spinal cord level, in an attempt to suppress autotomy behavior. The results show that autotomy was reduced by an average of 63% throughout the 8 week observation period. Catecholamine (CA) histofluorescent staining performed up to 120 days postoperatively (P0) revealed viable transplants in 75% of the rats. Transplant viability correlated with suppression of autotomy. This suggests that medullary chromaffin cells function as a local, long-lasting source of anti-nociceptive agents at the spinal segments which process input from the injured nerves. PMID- 2207687 TI - Disk-shedding in the rat retina: lithium dampens the circadian rhythm but potentiates the light response. AB - Disk-shedding in the rat retina undergoes a circadian rhythm. Chronic lithium treatment significantly dampens the rhythm in constant darkness, but does not alter the timing or amplitude of the peak in a light-dark cycle. Lithium potentiates light-elicited disk-shedding with a maximal effect at the end of the subjective light phase, when light alone evokes only a moderate response. Although serum lithium levels show a diurnal variation, retinal lithium concentration remains high throughout 24 h. Thus lithium induces alterations in retinal rhythms as well as in photoreceptor metabolism. PMID- 2207686 TI - Dissociation and culture of mechanosensory neurons for patch clamp analysis. AB - Single mechanosensory neurons were isolated from chordotonal organs of adult cockroach antennae. Transmission and scanning electron microscopy showed that the soma and part of the mechanosensory ending survived the dissociation. In culture, outgrowth occurred from the ending. Regions of cell membrane were accessible for patch clamp analysis and channels were recorded. The ability to record channel activity in isolated mechanosensory neurons will allow the study of mechanotransduction mechanisms at the membrane level. PMID- 2207688 TI - Spinules in axospinous synapses of the rat dentate gyrus: changes in density following long-term potentiation. AB - Following high frequency stimulation of the perforant path the density of axospinous synapses from the middle third of the molecular layer of the rat dentate gyrus did not change significantly. By contrast, within this synaptic population the density of axospinous synapses containing synaptic spinules increased markedly. We interpret these results in terms of a structural modification related to enhanced synaptic efficacy. PMID- 2207689 TI - The nervus terminalis in the chick: a FMRFamide-immunoreactive and AChE-positive nerve. AB - The chick terminal nerve (TN) was examined by immunocytochemical and histochemical methods. Molluscan cardioexcitatory peptide-immunoreactive (FMRFamide-ir) and acetylcholinesterase (AChE)-positive TN perikarya and fibers were distributed along olfactory and trigeminal nerves. FMRFamide-ir TN fibers terminated in the olfactory lamina propria and epithelium and in ganglia along the rostroventral nasal septum. This initial description of several populations of avian TN neurons should provide the foundation for future developmental studies of this system. PMID- 2207690 TI - In vivo and in vitro studies on the effect of the serotoninergic system on luteinizing hormone and luteinizing hormone-releasing hormone secretion in prepubertal and peripubertal female rats. AB - The present investigations were designed to assess the effect of the serotoninergic system on luteinizing hormone (LH) and LH-releasing hormone (LH RH) secretion in female rats aged 14 and 30 days. The administration of 5 hydroxytryptophan (5-HTP; 75 mg/kg i.p.) increased hypothalamic serotonin (5-HT) concentrations in both age groups, and did not affect hypothalamic norepinephrine (NE) concentrations or release. Serum LH levels were raised by 5-HTP in 14-day old, but not in 30-day-old rats. Basal and KCl- (28 mM) stimulated LH-RH release by incubated hypothalamic fragments was significantly enhanced when 5-HTP was injected previously to 14-day-old animals. In 30-day-old rats, 5-HTP treatment did not modify basal LH-RH release, and decreased the KCl-stimulated LH-RH output. Similarly, the addition of 5-HT (10(-7) M) to superfused hypothalamic fragments enhanced basal LH-RH release in 14-day-old rats and blocked the increment in LH-RH release evoked by KCl in 30-day-old rats. The present results show that in 14-day-old female rats, the serotoninergic system (activated in vivo by 5-HTP treatment, or in vitro by 5-HT addition) exerts a stimulatory effect on LH-RH, and thus, on LH release. On the contrary, in 30-day-old animals, stimulated LH-RH secretion was inhibited by 5-HT. Apparently, the hypothalamic NE system is not implicated in this response. The participation of this changing effect of 5-HT on LH-RH/LH release at the onset of puberty is postulated. PMID- 2207691 TI - The role of transmembrane pH gradients in the lactic acid induced swelling of astrocytes. AB - The swelling of astrocytes is an important component of the morbidity and mortality associated with ischemic brain trauma. In the ischemic brain, lactic acid levels rise dramatically with a concomitant acidification of the extracellular fluid. In this study we have measured the effects of elevated extracellular lactate and reduced extracellular pH (pHo) on astrocyte volume using the human astrocyte-derived cell line UC-11MG. Neither elevated lactate nor reduced pHo alone increased cell volume, but swelling of about 25% was measured when the cells were exposed simultaneously to 20 mM lactic acid and a reduced pHo of 6. The swelling was correlated with an approximately 4-fold increase in intracellular lactate as pHo was decreased from 8.0 to 6.0. As pHo was decreased intracellular pH also decreased, but much more slowly so that at acidic extracellular pH there was an inwardly directed proton gradient. The measured intracellular lactate concentrations closely followed the theoretical levels predicted by a model in which lactate transport is coupled to the inwardly directed proton gradient. Kinetic studies indicated that lactate transport is saturable with a Km of 3.8 mM, consistent with the model for facilitated cotransport of lactate with a proton or exchange of lactate for a hydroxyl ion. These data suggest that an important mechanism of postischemic astrocytic swelling is a proton driven, active accumulation of lactate to levels that result in a significant osmotic gradient of lactate at acidic pH. PMID- 2207693 TI - Mapping of spontaneous spike and wave discharges in Wistar rats with genetic generalized non-convulsive epilepsy. AB - Electrical activity was recorded in different parts of the brain in Wistar rats from a strain with genetic generalized non-convulsive epilepsy (GNCE or absence epilepsy). Movable bipolar electrodes were lowered stereotaxically by 1 mm steps into the brain in immobilized animals. Spontaneous spike and wave discharges (SWD) of the largest amplitude were recorded in the cortex and in lateral nuclei of the thalamus where they appeared occasionally to precede. Smaller amplitude SWD were recorded in the striatum, hypothalamus, tegmentum and substantia nigra. No SWD were recorded in limbic structures. Partial limbic seizures induced by the introduction of the electrode did not interfere with occurrence of cortical SWD. These results confirm the primacy of thalamocortical involvement in SWD of GNCE. The absence of spread to limbic structures and the implication of a precisely limited substrate in GNCE accounts for the clinical and pharmacological specificity of this particular kind of epilepsy. PMID- 2207694 TI - A 5-HT1-type receptor mediates the antinociceptive effect of nucleus raphe magnus stimulation in the rat. AB - The serotonin-containing raphe-spinal pathway has been implicated as playing an important role in analgesia. Several studies, however, have reported the inefficacy of traditional serotonin receptor antagonists at reversing the antinociceptive action of electrical stimulation in the raphe. In the light of recent reports on the existence of several types of 5-HT receptors in rat spinal cord, the present study investigated the ability of two antagonists, selective for two different 5-HT receptors to reverse the effects of focal electrical stimulation of the raphe magnus nucleus in the rat. Electrical stimulation of this nucleus resulted in selective antinociceptive as well as non-selective inhibitory effects on dorsal horn neurones. Both these effects were blocked by the ionophoretic application of a 5-HT1, but not a 5-HT2 receptor antagonist. The study presents data supporting the role of a spinal 5-HT receptor in mediating stimulation-produced analgesia from the nucleus raphe magnus and further, furnishes evidence that the 5-HT1 receptor is involved in antinociception at the spinal level. PMID- 2207692 TI - Electrophysiological properties of embryonic neocortex transplants replacing the primary visual cortex of adult rats. AB - Solid pieces of the occipital neocortex derived from 17-day rat fetuses were placed in a cavity formed by complete unilateral aspiration of the primary visual cortex in adult rats. Vital labeling of the brain with bisbenzimide was used to differentiate grafts from the host brain tissue. 2 to 10 months after operation electrophysiological experiments were performed in which neuronal activity and field potentials in transplants were recorded in response to sensory and electrical stimulation of the host brain. This study shows that in a large portion of the transplants (14 out of 25): (1) the majority of neurons (183/270) are controlled by visual stimuli and many of them respond to electrical stimulation of the lateral geniculate body (53/62) and the homotopic sites of the contralateral neocortex (28/62); latencies of these responses are within the ranges typical of the normal visual cortex; (2) there is a topical representation of the visual field on the transplants; (3) receptive field sizes, the preference to stationary flashes or to moving visual stimuli and the temporal response pattern of the grafted neurons are similar to those of the primary visual cortex. However, the field potentials evoked visually were recorded only in part of the transplants (8/14) which revealed clear neuronal visual responses, and field potential depth profile differed from that in visual cortex in situ. The functional organization of the transplants remained unchanged throughout the long time testing. Taken together, these results suggest that after primary visual cortex removal, fetal neocortex transplants may be able to replace functionally the damaged neural circuitries of the host brain. PMID- 2207697 TI - Relationship between free-running period and motor activity in blinded rats. AB - The free-running rhythms of motor activity in blinded rats were measured by two different devices, an Automex or a running wheel. The period of free-running rhythm measured by a running wheel was likely to be shorter than that measured by an Automex, indicating that subtle environmental difference, such as whether a cage is equipped with a wheel or not, can affect the free-running period. In addition, we found a negative correlation not only between the free-running period measured by a running wheel and that measured by an Automex, but between the free-running period and the number of wheel revolutions per day. This is the first evidence that motor activity, other than the external factors such as light intensity and temperature, may be related to change in the free-running period. PMID- 2207695 TI - Cocaine: effect on spinal projection neurons in the rat. AB - In the anesthetized rat, systemic cocaine at an analgesic dose (25 mg/kg, IP) had no general influence on spontaneous activity in nociceptive spinoreticular tract neurons or in rostrally projecting low-threshold mechanoreceptive neurons of the spinal dorsal horn. Peripherally evoked activity was moderately (mean: 30%) reduced in 43% (6/14) of the spinoreticular tract neurons, whereas in 50% of them there was no marked change in evoked activity by cocaine. Evoked activity was slightly reduced in 25% (2/8) of the low-threshold mechanoreceptive neurons and not changed in 75% of them. The suppressive effect of a distant conditioning noxious stimulus on responses to spinoreticular tract neurons was enhanced by cocaine in 3/6 of the spinoreticular tract neurons. Primary afferent terminal excitability of A-fibers was slightly increased following cocaine as indicated by the increased amplitude (mean: 24%) of the antidromically evoked compound action potential recorded from the sural nerve. It is concluded that the previously shown marked enhancement of spontaneous activity in the bulborecticular formation is generated supraspinally. Thus, while cocaine-induced analgesia appears to be due primarily to supraspinal mechanisms, the present results suggest that spinal mechanisms are also involved possibly presynaptically. PMID- 2207696 TI - Dopamine and ACh involvement in plastic learning by hypothalamic neurons in rats. AB - Unit activity in the rat lateral hypothalamus (LHA) was recorded during discrimination learning of cue tone stimuli (CTS). CTS+ predicted reward (glucose or intracranial self-stimulation); CTS- predicted aversion (electric shock or tail pinch); and all behavior responses were by the same act, licking. Roles of the LHA dopaminergic and cholinergic systems in CTS learning were investigated by electrophoretic application of dopamine (DA) and acetylcholine (ACh), and their antagonists. The CTS+, the predicted reward and DA, all had similar effects (inhibition) on many LHA neurons; and these were all opposite to the effects (excitation) of CTS-, the predicted aversion, and ACh. Neural responses to CTS+ were blocked by spiperone, and responses to CTS- were blocked by atropine. Sensitivity of LHA neurons to DA was reduced by extinction of CTS+ learning for reward, and sensitivity to ACh was reduced by CTS- learning for aversion. The data suggest that afferent DA and ACh inputs to LHA neurons are essential for plastic CTS+ and CTS- learning. PMID- 2207698 TI - Involvement of the entopeduncular nucleus and the habenula in methamphetamine induced inhibition of dopamine neurons in the substantia nigra of rats. AB - The lateral habenula receives massive afferents from dopamine-rich forebrain areas through the stria medullaris and sends efferents to mesencephalic dopaminergic systems through the fasciculus retroflexus. In the present study, effects of electrolytic lesions of the habenula, transections of the stria medullaris, and kainic acid-induced lesions of the entopeduncular nucleus on methamphetamine-induced inhibition of substantia nigra dopamine neurons were investigated in rats. Following these lesions or transections the methamphetamine induced inhibition on the dopamine neuronal activity was significantly attenuated compared to those in control animals with sham lesions or sham transections. Intravenous administration of methamphetamine at a dosage of 6.4 mg/kg produced only a 62.7 to 71.2% inhibition in lesioned or transected animals, whereas in control animals the activity of dopamine neurons was almost completely inhibited with this dose. The amounts of methamphetamine required to induce 50% inhibition of dopamine neurons in lesioned or transected animals was 3.3 to 4.7 times greater than those in control animals. There was no significant difference in cumulative dose-response curves between habenular-lesioned, stria medullaris transected and entopeduncular-lesioned animals. These results, along with other findings, indicate possibly that the pathways running through the entopeduncular nucleus, the stria medullaris, the habenula, probably the lateral habenula, and the fasciculus retroflexus are involved in a feedback loop from the striatum to the substantia nigra and regulate the activity of dopamine neurons. PMID- 2207699 TI - Fate of septohippocampal neurons following fimbria-fornix transection: a time course analysis. AB - Neurons in the medial septum (MS) and vertical limb of the diagonal band (vDB) undergo degenerative changes following transection of their axons. These changes have been well studied by histological techniques such as Nissl stains and immunocytochemistry. A dramatic loss of stained neurons occurs following axotomy and this has been interpreted as indicative of neuronal death. However, since the staining intensity and the size of affected neurons may be reduced by axotomy, it is possible that the apparent neuronal death may actually be due to a decrease in somal size or the ability to detect neurons by routine histological methods. The present study describes the effects of axotomy on MS and vDB neurons which have been labeled by hippocampal injections of the retrograde tracer, Fluoro-Gold (FG), prior to transection of the fimbria-fornix and supracallosal stria. The number of FG-labeled neurons in the MS decreased by 21% at three weeks, 36% at six weeks, and 31% at ten weeks after fimbria-fornix transection. The reduction was statistically significant at 6 and 10 weeks. The number of FG-labeled neurons in the vDB showed no reduction at three weeks but was decreased by 31% and 37% at six and ten weeks, respectively. This was statistically significant only at 10 weeks. By comparison, the number of neurons immunoreactive for choline acetyltransferase (ChAT) was reduced by 75-80% at these time points. The size (area and diameter) of FG-labeled somata decreased in both the MS and vDB within three weeks following fimbria-fornix transection and remained relatively constant at the six- and ten-week time points.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2207700 TI - Effect of central tachykinins, alone and with angiotensin II, on drinking in pigs and goats. AB - Central administration of the tachykinins, eledoisin or physalaemin has been reported to produce significant water intake in pigeons but inhibition of stimulated drinking in rats. In this paper it is shown that high and low doses of these two tachykinins injected centrally in two much larger species, goats and pigs, did not produce any significant drinking. Furthermore, in pigs, physalaemin, but not eledoisin, attenuated AII stimulated drinking (576 +/- 64 ml AII alone, versus 456 +/- 131 ml AII + eledoisin, not significant, and 124 +/- 89 ml AII plus physalaemin, p less than 0.01, in the same 5 pigs) and also, especially at the higher doses, induced general locomotor activation. However, in goats neither tachykinin interfered with drinking induced by central injection of 300 ng AII. These results show that in pigs and goats the tachykinins, eledoisin and physalaemin, are not effective dipsogens and that one of the possible reasons for the inhibitory action of physalaemin on AII-induced drinking may be through the general locomotor activation and not through a direct effect on the central AII system. PMID- 2207701 TI - Neonatal 5,7-DHT lesions upregulate [3H]mesulergine-labelled spinal 5-HT1C binding sites in the rat. AB - To delineate the involvement of spinal 5-HT1C receptors in supersensitivity and recovery following neonatal 5,7-DHT lesions, we injected rats on postnatal days 2 and 5 with 5,7-DHT or vehicle by intraperitoneal (IP) or intracisternal (IC) injection. [3H]Mesulergine-labelled sites measured 4 or 14 weeks later exhibited a significant increase (+35% for IP and 27% for IC) in Bmax without changes in Kd or nH. Spinal 5-HT content was significantly reduced (-80 to 89%) by either route of 5,7-DHT injection. These data describe novel upregulation of spinal 5-HT1C receptors in rats with neonatal 5,7-DHT lesions. Spinal 5-HT1C receptor upregulation may contribute to the behavioral supersensitivity to L-5 hydroxytryptophan (L-5-HTP) in rats with 5,7-DHT lesions. It does not explain the behavioral recovery we found previously only after IP 5,7-DHT injection. PMID- 2207702 TI - Morphological diversity of ependymal cells in tissue culture. AB - Ependymal cells were visualized in primary cultures of cerebral cortex from rat using an immunohistochemical staining technique. Five different morphological subtypes of cuboidal ependyma were recognized: 1) round, 2) triangular, 3) columnar, 4) cone- and spindle-shaped, and 5) large pleomorphic cells. These cells varied in size and almost all possessed cilia. Two distinct forms of tanycyte ependyma were detected based on the presence of cilia. These features reflect a significant level of development of the ependymal cells in culture and may correspond to functional diversity within this group. PMID- 2207703 TI - Estradiol increases the dendritic length of ventromedial hypothalamic neurons in female Syrian hamsters. AB - We examined the effects of ovarian hormones on dendritic architecture of neurons in the ventromedial nucleus of the hypothalamus in female Syrian hamsters. Treatment with 10 micrograms of estradiol benzoate for two days, or estradiol benzoate for two days followed by an injection of 500 micrograms of progesterone, increased the total dendritic length of ventromedial nucleus neurons by almost 50% compared with neurons from the ventromedial nucleus of ovariectomized, oil treated females. Neurons in a control region, the dorsomedial nucleus of the hypothalamus, were unaffected by these hormone treatments. These results demonstrate that steroids can induce changes in dendritic structure within 48 hr, suggesting that such morphological reconfiguration of hypothalamic neurons may underlie variations in behavior associated with the female's 4-day estrous cycle. PMID- 2207705 TI - The effects of intraventricular injections of bombesin on temperature selection in the rat. AB - The purpose of these experiments was to elucidate further the possibility that intraventricular injections of bombesin (BBS) lower the set point around which an animal regulates its core body temperature. In an attempt to prevent a confounding of general activity and thermoregulatory behavior which occurred in earlier work, a horizontal temperature gradient was used. Intraventricular injections of bombesin resulted in the selection of temperatures that were approximately 9-13 degrees C colder than those selected by animals following control injections. Additionally, the increase in core body temperature observed following control injections was reversed by the highest dose of bombesin. No significant alterations in general locomotor activity were observed. These findings suggest that bombesin may act centrally to reduce the set point around which behavioral responses are regulated. PMID- 2207704 TI - Involvement of corticotropin-releasing factor in the anorexia induced by exercise. AB - The role of corticotropin-releasing factor (CRF) in the sex-dependent anorexia induced by exercise was investigated in male Wistar rats. Each rat was implanted with a permanent guide cannula that was stereotaxically positioned close to the right lateral ventricle of the brain. During the recovery period, which lasted 10 days, rats were accustomed to eat three meals per day. The onset of each meal occurred every 8 hours. During a meal, rats were allowed free access to a pelleted stock diet for one hour. Ten days after the surgery, rats were injected in the right lateral ventricle of the brain with either saline or 100 micrograms of alpha-helical CRF (9-41), a selective CRF antagonist. Fifteen minutes after the injections, half of the rats were forced to exercise while the others were allowed to rest. The exercise consisted of a moderately intense period of running on a motor-driven treadmill during 40 minutes. Immediately after the period of exercise, animals were offered food, and the amount eaten during the meal period was carefully measured. The results indicate that the exercised rats ate less food than resting animals when saline was infused prior to subjecting the animals to running. In addition, in saline-treated animals, growth of exercised rats was slower than that of resting rats during the day following exercise. Contrastingly, in rats infused with alpha-helical CRF (9-41) exercise exerted no effect on food intake, neither did it reduce body weight gain of the rats. The present results suggest that CRF plays a major role in the anorexia caused by exercise in male rats. PMID- 2207706 TI - Long-lasting elevation of alanine in brain produced by the antidepressant phenelzine. AB - Time- and dose-response studies were conducted to determine the effects of the antidepressant and antipanic drug phenelzine (a monoamine oxidase inhibitor) on whole brain levels of the aliphatic amino acid alanine. At a dose of phenelzine of 15 mg/kg IP, there was a significant increase in brain levels of alanine up to 16 hr after drug administration. Dose studies at 4 hr indicated that the alanine elevation after phenelzine was a dose-dependent effect. PMID- 2207708 TI - Involvement of the raphe in the respiratory effects of gigantocellular area activation. AB - Previous reports indicate that the nucleus reticularis gigantocellularis (NGC) of the brainstem reticular formation is involved in inhibitory respiratory and cardiovascular reflexes. Stimulation of portions of the nearby bulbar raphe complex, specifically the raphe magnus (RM), have also been shown to suppress phrenic activity and to decrease blood pressure and heart rate. Since synaptic connectivity between the NGC and the RM has been demonstrated, we hypothesized that the RM may be involved in the cardiopulmonary effects of NGC stimulation. This study found that electrolytic lesions in the raphe magnus attenuated the inhibitory respiratory effects but not the cardiovascular suppression due to NGC stimulation. Lesions in the raphe magnus also lowered resting blood pressure and resting breath frequency. We conclude that the RM may mediate part of the NGC mediated respiratory effects. PMID- 2207707 TI - The ACE inhibitor [3H]SQ29,852 identifies a high affinity recognition site located in the human temporal cortex. AB - The angiotensin converting enzyme (ACE) inhibitor [3H]SQ29,852 identified a single high affinity recognition site (defined by 10.0 microM captopril) in the human temporal cortex (pKD 8.62 +/- 0.03; Bmax 248 +/- 24 fmol mg-1 protein, mean +/- S.E.M., n = 4). ACE inhibitors and thiorphan competed to a similar level for the [3H]SQ29,852 binding site in the human temporal cortex with a rank order of affinity (pKi values mean +/- S.E.M., n = 3), lisinopril (9.49 +/- 0.02), captopril (9.16 +/- 0.08), SQ29,852 (8.58 +/- 0.04), epicaptopril (7.09 +/- 0.08), fosinopril (7.08 +/- 0.05) and thiorphan (6.40 +/- 0.04). Since this rank order of affinity is similar to the affinity of these compounds to inhibit brain ACE activity it is concluded that [3H]SQ29,852 selectively labels the inhibitor recognition site of ACE in the human temporal cortex. PMID- 2207711 TI - Neurochemical recovery in the neocortex after colchicine lesions of the nucleus basalis magnocellularis in rats. AB - Neurochemical recovery was investigated in male, Fischer-344 rats up to 3 months after lesions of the nucleus basalis. Bilateral injections of colchicine (1.0 micrograms/site) into the nucleus basalis magnocellularis (NBM) resulted in a 30% decrease in choline acetyltransferase (ChAT) activity in frontal cortex 4 weeks after surgery, compared to unlesioned controls. ChAT activity in the frontal cortex gradually recovered to control levels by 12 weeks. The loss of ChAT immunoreactive neurons in the NBM observed 4 weeks after surgery was still evident 12 weeks after surgery. These results suggest that surviving cholinergic neurons in the NBM contribute to recovery of ChAT activity in the neocortex. PMID- 2207709 TI - A novel autoantibody from a rabbit preimmune serum that immunostains myelinated nerves of the brain. AB - Preimmune serum from a rabbit was found to contain antibodies that selectively immunostained myelin in brain sections of the rat. It also reacted with oligodendroglial cells in culture as shown by double labeling with galactocerebroside. On Western blots of two-dimensional electrophoretic gels of rat cortex, this antiserum recognized a 46 kD protein with a basic pI. The presence of this protein within myelin may help identify possible cellular mechanisms of myelination and the autoimmune serum might be useful in structural studies of myelin. PMID- 2207710 TI - 5-Aminoimidazole-4-carboxamide riboside (AICAr) administration reduces cerebral ischemic damage in the Mongolian gerbil. AB - Cerebral ischemic damage in gerbils was assessed by locomotor activity studies and histopathological examination of the hippocampal CA1 pyramidal cell layer. Pretreatment with AICAr (50 and 500 mg/kg) 30 min prior to a 5-min ischemic episode in unanesthetized gerbils, significantly attenuated the degree of ischemic neuronal damage as measured by either technique with the 500 mg/kg dose; the 50 mg/kg dose, although showing a trend, was not significant. A potential mechanism for AICAr-induced cerebroprotection may be that it is metabolized to uric acid, a free radical scavenger. PMID- 2207712 TI - Origin of some enkephalin-containing afferents to the ventro-medial region of the globus pallidus in the rat. AB - The retrograde transport of WGA-HRP adsorbed to colloidal gold was combined with the indirect immunoperoxidase technique to study the origin of enkephalin containing afferents to the medial and ventral regions of the globus pallidus (GP). On the injected side, the nerve cell bodies labeled retrogradely or double labeled were numerous in the central nucleus of the amygdala (ACe), scattered in the bed nucleus stria terminalis (BNST) and few in the fundus striati. In the ACe, approximately 40% and 20% of the retrogradely labeled perikarya were found immunoreactive for Met-enkephalin and Leu-enkephalin, respectively, whereas they were only 30% and 15% in the BNST. It is concluded that the enkephalinergic afferents of the ventro-medial region of GP, which contains the basal nucleus of Meynert in the rat, are largely of limbic origin. PMID- 2207713 TI - A preliminary study of homotopic fetal cortical and spinal cotransplants in adult rats. AB - Neocortical and spinal tissue from a given E16-17 rat fetus were homotopically transplanted into lesion sites of adult rats which had undergone combined cortical and complete lower thoracic spinal cord lesions. Spinal cord transplants were placed either directly into the gap in host spinal cord or embedded in a collagen matrix. Animals were killed from 4 days to 8 months and tissues were processed for light microscopy. All cortical transplants survived and integrated with host brain. Many axons appeared to grow between the cortical transplant and subjacent host parenchyma. Only collagen-embedded spinal transplants survived. At 8 months, two animals underwent spinal cord transection and HRP implantation two vertebral segments rostral to the spinal cord transplantation site. Both animals revealed HRP-labeled neurons in the cortical transplants. It was concluded that 1) homotopically transplanted fetal cortical tissue can survive and may be capable of extending axons to midthoracic levels, and 2) a collagen matrix may enhance the survival of fetal tissues transplanted into a complete gap in host spinal cord. PMID- 2207715 TI - Conditioning-related changes of unit activity in the dorsal lateral geniculate nucleus of urethane-anaesthetized rats. AB - Changes in geniculate unit activity of urethane-anaesthetized and freely moving rats were investigated during conditioning. The conditioned stimulus (CS) was a flash which was paired with an electrical stimulation of the tail as unconditioned stimulus (US). The discharge rates evoked by the CS during forward conditioning were significantly higher in responding units than those evoked by reversal of CS and US (backward conditioning) or by pseudoconditioning. Tail stimulation alone did not cause significant changes in the firing rate of most of the neurons. In 25% of the investigated neurons the facilitation of activity evoked by forward conditioning persisted during an extinction period of more than 15 min. The effect of conditioning on neuronal activity appeared to be comparable in urethane-anaesthetized rats and in freely moving ones which responded to the US with a slight freezing behavior. PMID- 2207716 TI - Beta-endorphin in the male rat pituitary: testosterone influences the effect of cocaine. AB - In order to determine if the effect of cocaine on the concentration of immunoreactive beta-endorphin (IR-BE) in the anterior pituitary (AP), neurointermediate lobe of the pituitary (NIL) and hypothalamus was modulated by gonadal steroid, the following groups of animals were studied: a) castrated male rats treated with vehicle, b) castrated male rats treated chronically with cocaine (daily for 10 days), c) castrated male rats treated with testosterone propionate (TP) and d) castrated male rats treated with TP and chronically administered cocaine. Only in castrated rats given TP did cocaine induce a significant increase in the concentration of IR-BE in the AP. The concentration of IR-BE in the NIL was increased by cocaine and was not influenced by the presence or absence of TP. Hypothalamic IR-BE remained unchanged in response to cocaine and was decreased by TP. Column chromatography revealed that TP and cocaine interacted to modulate the amount of beta-endorphin relative to beta lipotropin in the AP. These findings suggest that in the male rat, the effect of cocaine on the concentration of IR-BE in the AP is modulated by the gonadal steroid environment. By contrast, gonadal does not appear to play a role in the effect of cocaine on the concentration of IR-BE in the NIL. PMID- 2207714 TI - Local versus indirect action of glucose on the lateral hypothalamic neurons sensitive to glycemic level. AB - The neuronal activity in the lateral hypothalamus may be affected by moderate changes in blood glucose. The present study aimed to specify the direct or indirect origin of this sensitivity to glycemia, by recording the unit responses in this area to both local glucose application (by means of microelectrophoresis) and hyperglycemia (induced by an IV glucose injection). The activity of approximately 25% of the recorded LHA neurons was modified by topically ejected glucose. However, a large majority of these neurons sensitive to local glucose failed to respond to hyperglycemia. Conversely, only 1/3 of the glycemia sensitive cells responded in the same direction to systemic and local glucose administration. Therefore, the response to IV glucose of the other 2/3 glycemia sensitive cells could not result from the direct action of glucose molecules on these neurons, but probably involved an indirect afferent pathway conveying the glycemic cues from some central or peripheral glucose sensors to the cell under investigation. PMID- 2207718 TI - Copulatory behavior is controlled by the sexually dimorphic nucleus of the quail POA. AB - The medial preoptic nucleus (POM) of the quail preoptic area is sexually dimorphic and testosterone sensitive. Stereotaxic implantation of needles filled with crystalline testosterone demonstrated that the POM is a critical site of steroid action in the control of copulatory behavior. Only implants located in the POM reliably restored the behavior in castrated birds. Implants around the nucleus weakly activated the behavior; those which were distant by more than 200 microns were totally inactive. Electrolytic lesions confirmed the role of the POM in the control of copulatory behavior. The percentage of the POM which was lesioned was highly correlated to the behavioral deficit while the absolute size of the lesion was not. Electrolytic lesions in or around POM also significantly decreased the volume of the nucleus suggesting that the afferents and efferents of the nucleus are required for its full development. The total volume of the POM was correlated with the sexual behavior of the birds. The morphological changes in POM observed following exposure to testosterone probably represent the signature of the behavioral effects of the steroid. The sexually dimorphic testosterone-sensitive POM is therefore an excellent animal model to study the brain-steroid interactions which mediate the activation of male reproductive behavior. PMID- 2207719 TI - Functional recovery after limbic lesions in monkeys. AB - Ten monkeys received lesions of either the hippocampus, or the amygdala and hippocampus, or the anterior and medial thalamus (each group with two monkeys), or of all these structures together with additional septal lesions (four monkeys). Postoperatively, the monkeys were trained in tasks of visual and spatial reversal, several concurrent object discriminations, delayed nonmatch-to sample, and in an angle threshold discrimination task. Their performance was compared to that of five healthy or sham-operated control monkeys. The single- or double-lesioned monkeys were impaired in the delayed nonmatch-to-sample task and the angle threshold discrimination, whereas monkeys with five-fold lesions were unimpaired in these tasks. Correlations between brain volume loss and behavioral performance indicated negative coefficients for the delayed nonmatch-to-sample task ("delays": rs = -.59, "lists": rs = -.20) and the angle threshold discrimination (rs = -.60). It is concluded that monkeys with massive limbic lesions display a more effective postlesion reorganization than monkeys with smaller limbic lesions; however, reliability of this effect must be proved by future work with a larger sample. Furthermore, the missing impairments of massively lesioned monkeys especially in the delayed nonmatch-to-sample task also indicate that the limbic targets lesioned here may not be as exclusively involved in mnemonic information processing as suggested earlier. PMID- 2207720 TI - Single unit response of neurons within the hamster suprachiasmatic nucleus to GABA and low chloride perfusate during the day and night. AB - Using the in vitro hamster hypothalamic slice preparation, the effects of GABA and 80% chloride (Cl-) reduced medium on the single unit activity of SCN neurons was investigated. GABA 10(-4) M produced inhibitory responses in 55% of the 69 SCN neurons examined. No statistically significant day-night difference was observed in either the percentage of SCN units responding to GABA, or in their threshold response. During the day 80% Cl- reduced medium had an excitatory effect on SCN neurons; however, following the return to normal Cl- concentrations a transient, but significant inhibition was observed. During the night, 80% Cl- reduced medium produced an excitatory response similar to that observed during the day, but no inhibition following return to the medium containing normal Cl- concentrations. Only during the night was Cl- reduced medium found to initiate activity in a dose-dependent manner in some silent cells. No significant day night difference in response to 80% Cl- reduced medium occurred in neurons of the paraventricular nucleus of the hypothalamus. These results indicate that SCN neurons whose activity is mediated by Cl- may be involved in the control of circadian rhythms. PMID- 2207717 TI - The pressor response to spinal cholinergic stimulation in spontaneously hypertensive rats. AB - Several laboratories have demonstrated that central cholinergic stimulation in spontaneously hypertensive rats (SHR) results in an exaggerated pressor response as compared to normotensive (NT) controls. Recent studies in this laboratory have demonstrated a spinal cholinergic pressor system in the NT rat. The purpose of this study was to determine whether the pressor response to spinal cholinergic stimulation is enhanced in SHR. In freely moving rats, intrathecal injection of neostigmine or carbachol (1-5 micrograms) produced a dose-related hypertensive response in both strains of rats. While both agonists produced similar maximal increases in blood pressure in NT rats, the pressor responses to both agonists were significantly greater in SHR. The tachycardic responses to IT injection of cholinergic agonists were also significantly greater in SHR. These differences were more apparent at the lower doses where, for example, the pressor response to 1 microgram of agonist in the SHR was increased by 123% and 109% of the response in NT rats for carbachol and neostigmine, respectively. Since both direct and indirect acting agonists produced greater responses in SHR, and spinal depletion of acetylcholine did not reduce blood pressure in SHR, it is most likely that spinal cholinergic systems ascend to higher centers to elicit pressor responses. In the case of the SHR, these higher centers may be supersensitive to cholinergic stimulation. PMID- 2207721 TI - [The effect of verapamil on experimental atherosclerosis in rabbits]. AB - The model of atherosclerosis was elaborated by administration of cholesterol to rabbits in daily doses of 70 g per animal over a period of 3 months. The model served to study the effect of the calcium entry blocker Verapamil as to its potential capacity of affecting the extent of atherosclerotic changes. The thoracic aorta, the abdominal aorta, the right coronary artery and the apex of the myocardium were removed for histological evaluation. Atherosclerotic changes were assessed by light microscopy using the method of quantifying the thickening of the intima of vessels. The extent of atherosclerotic changes in the coronary arteries and arterioles was evaluated morphometrically. Further the presence and extent of necroses of the myocardium as well as endothelial proliferation in the capillaries of the cardiac muscle were recorded. Evaluation of the obtained results calculated as percentage of the presence of findings demonstrated a significant protective effect of Verapamil on the parameters studied. PMID- 2207722 TI - [The effect of diazepam on the electroretinogram]. AB - The effect of some drugs on electric potentials of the retina has been described in the literature. Data on the effect of drugs of the group of benzodiazepines on electric potentials of the retina in man have not come to our attention. In the present study diazepam was found to affect substantially the studied parameters of the electroretinogram. An inhibitory effect of diazepam on the electric response of the retina was established. The period of latency and that of culmination of the electroretinogram were found to be most intensively affect. PMID- 2207723 TI - [Analysis of left ventricular function using 2-dimensional and pulsed Doppler echocardiography in type I diabetics]. AB - In 44 patients with type I diabetes mellitus divided into a group of 29 patients (mean age 25 years, duration of diabetes 6 years on the average) without microangdiopathic complications and into a second group of 15 patients (mean age 31 years, duration of diabetes 16 years on the average) with retinopathy and/or nephropathy, parameters of cardiac function were studied by means of two dimensional (2D) and pulsed Doppler (PD) echocardiography. The obtained results were compared with findings recorded in a third group of 20 healthy subjects (mean age 29 years). 2D measurements of parameters such as ejection fraction, diastolic diameter of left ventricle (LV), thickness of septum and posterior wall did not reveal any significant differences between the groups studied. On analysing diastolic function expressed by maximal velocity of rapid LV filling (E), atrial systole (A), E/A ratio, and atrial systole ejection time (AET), compared to the control group, the second group presented with significantly decreased E, increased A, and reduced E/A (p less than 0.001). In the first group only a shortened AET (p less than 0.01) was recorded. AET was changed also in the second group and was found to be inversely correlated with the duration of the disease, r = -0.43, p less than 0.05). PMID- 2207724 TI - [Lipid composition of the myometrium during labor]. AB - Lipids represent one of the basic components of each cellular and subcellular membrane of the myometrium and their fluidity has a strong influence upon membrane function. Human myometrium was obtained at cesarean sections. Lipids were separated by one-dimensional thin layer chromatography. The chromatoplates were determined on the densitometer Shimadzu CS 930. Lipid profile of the myometrium was studied before the 37th week of pregnancy, at term without contractile activity, further during at term labor with normal contractile activity and at failure of myometrial contractility. Analysis of the obtained data showed changes in lipid fluidity, namely a decrease before the 37th week of pregnancy and at failure of myometrial contractions during at term labor. The decrease of fluidity was caused by a higher content of total cholesterol and a lower content of total phospholipids in the myometrium. PMID- 2207725 TI - [Microscopic diagnosis of mixed and mesenchymal tumors of the mucosa and uterine body]. AB - A series of 452 with 831 precancerous and tumorous lesions of the corpus uteri is presented. The series was obtained by analyzing the authors' own series of bioptic findings covering the period of two years. Some problems arising at the evaluation of proliferating myogenic and stromal precancerous and tumorous lesions are pointed out. "Classical" types of leiomyomas were found to be predominant, amounting to 78.5% of tumors recorded at the studied site. Of the total number of tumors of the corpus uteri, malignant tumors constituted only 8.5%. On evaluating the series of malignant tumors of the corpus uteri epithelial malignant tumors (94.3%) were overwhelmingly prevailing over sarcomatous tumors. Attention is called to problems of histological evaluation of prognosis of mesenchymal and mixed tumors. Literary data as well as the authors' own observations indicate the necessity of exact and particularly of differentiated histological evaluation of the described tumors. PMID- 2207727 TI - [Treatment and reconstruction of bullet wounds of the calf]. AB - The paper describes complete management of bullet wounds of the crus. After thorough primary surgical treatment and fixation of the fracture the authors recommend the method of muscle flap of the soleus muscle and anterior tibial muscle and the method of musculocutaneous flap of the gastrocnemius muscle to achieve reconstitution of soft tissues. In fractures with tissue loss, after healing of the reconstituted areas of soft tissues, they advocate plastics with sponge and corticosponge grafts. Of the 12 bullet wounds of the extremities treated 3 were injuries of the crus. PMID- 2207726 TI - [Traumatic rupture of the diaphragm]. AB - Traumatic ruptures of the diaphragm occur most frequently at blunt injuries of the abdomen or thorax as a component of polytraumatism. At the acute stage they present a serious diagnostic problem since signs of polytrauma are predominant. The authors report 3 cases of traumatic rupture of the diaphragm with thoracotomy as the therapeutic approach. The first patient presented with severe polytraumatism and shock, rupture of the diaphragm, pericardium and lungs, along with serial fracture of the left ribs. The second patient was not in shock, he had suffered serial fracture of the left ribs and fracture of the pelvis. In both these cases of blunt injury to the thorax, careful examination of the patients resulted in early diagnosis and surgery. The third patient presented with open injury of the right side of the thorax, injured diaphragm and liver, serial fracture of the ribs, fractured sternum, and was in a state of deep shock. There was no mortality, all three patients recovered. PMID- 2207728 TI - [Infectious diseases and the liver. (Report from a symposium in Basel, October 12 14 1989)]. PMID- 2207729 TI - [The effect of chronic stress on the activity of the sympathetic-adrenomedullary system]. AB - Plasma levels of adrenaline (ADR) and noradrenaline (NA) belong to the best parameters of activity of the sympatho-adrenomedullary system (SAS). Introduction of a sensitive radioenzymatic method for the determination of catecholamines in small volumes of plasma (0.05 ml) and observing conditions of stressless blood collection by means of an indwelling catheter made in possible to determine basal plasma catecholamine levels and their dynamics during stress. Changes in plasma catecholamines were studied in acute and chronic stress (continual or intermittently repeated) in three stress models: 60-day hypokinesia, immobilization (IMO) repeated over 30 days, and 14-day or one-day handling of the rat for 1 minute. On first exposure to the given stressor the plasma levels of both catecholamines studied were increased. In the course of 60-day hypokinesia as well as during one- or 14-day handling plasma ADR levels returned to virtually resting values, plasma NA levels, however, remained at equally high values as recorded at the first exposure. During 30-day IMO basal values of ADR and NA in plasma were elevated, yet the catecholamine response to the last IMO was reduced compared to the first exposure. Under the effect of mild chronically acting stressors a dissociation was observed in the changes of plasma catecholamine levels: ADR failed to exhibit further increases, whereas NA kept significantly rising all over the period of the activity of the stressor. This differentiated activation of plasma catecholamines suggests the existence of different regulatory regions in the CNS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2207730 TI - [Characteristics of new approaches for evaluation of embryotoxic effects of chemical substances]. AB - New approaches to the evaluation of embryotoxic effects of xenobiotics are characterized in the light of mother--fetus interrelationship. The first part of the paper analyzes problems of evaluating maternal and embryofetal toxicity and substantiates the necessity of sensitive selection and precise evaluation of individual parameters of toxicity. The second part presents a survey of classical testing procedures and of alternative methods used in assessing the safety of new drugs. The third part characterizes methods of quantitative determination of risks inherent to chemical substances. A detailed description of the principles of the new method is presented which is based on the interrelationship of maternal and embryofetal toxicity (adult/developmental--A/D). The acceptability of the new method has been verified experimentally on evaluating some new prospective drugs according to standard teratological studies. PMID- 2207731 TI - [Irradiation of the population of the West Slovakia Region by atmospheric fallout of 90Sr and 137Cs from 1965 to 1988]. AB - The results of the survey show that as a consequence of the nuclear accident in Chernobyl contamination of foodstuffs with radioactive substances caused in May 1986 and additional irradiation of the population of the West Slovakian region which amounted to approximately 10-20% of the dose load derived from natural sources (cosmic radiation, radioactive substances present in the earth crust, in building materials, etc.). The mean dose load of the population was roughly 8 times higher in 1986 than in 1965, when tests of nuclear weapons had been carried out in the atmosphere and when systematic monitoring of radioactivity in foodstuffs had been implemented in the West Slovakian region. Contamination of the environment due to nuclear weapon tests reached the highest values in 1962 1963 when the dose load of the population can be assumed to have been 2-3 times higher than in 1965. In the locality of the nuclear power plant Jasl. Bohunice contamination of foodstuffs with radioactive substances was in the period of operation of the plant at the level of foodstuff contamination recorded at the reference site. PMID- 2207732 TI - [Method of determining functional age from the aspect of immunologic markers of aging]. AB - In a series of 310 subjects partial functional immunochemical age was determined by the method of multivariant linear regression. The authors suggested equations for the determination of partial functional immunochemical age, separately for men, women, and mixed groups, as well as for the determination of global functional age by using parameters of other systems of the body. A possible correction of the equations is discussed with the aim to eliminate the phenomenon of distorted results in the extreme positions of the chronological age axis. The contribution of the method of assessing partial functional immunological age to the selection of relevant markers of aging of the immune system is substantiated and its importance in justifying geroprotective and therapeutic procedures is emphasized. PMID- 2207733 TI - [New methods of artificial respiratory ventilation]. AB - High frequency ventilation, a new nonconventional method, has been introduced into clinical practice also in Czechoslovakia, where mainly high frequency jet ventilation (HFJV) is being developed. The HFJ ventilator Best-2 (Konstrukta, Trencin) and Chirajet (Chirana, Stara Tura) which enable HFJV with a multijet generator are used. These equipments reduce inadvertent positive end expiratory pressure by means of an expiration jet and are so designed that Brychta's impulse and expulse regimen can be used to advantage at programmed lavage of the lungs and at selective ventilation of individual parts of the lungs. The paper presents the basic principles of HFJV as well as the author's experience in using this method of ventilation in experimental animals. PMID- 2207734 TI - [A scanning electron microscopy study of the normal rabbit appendix]. AB - The surface relief of the mucous membrane of the normal rabbit appendix was studied under scanning electron microscopy. Two different types of surface relief were identified. One consisted of relatively regular crests and grooves of the mucosa, the other one exhibited scattered crater-like openings into which "heads of lymphatic nodes" were inserted to varying extent and which were separated from the surface mucosa by broad alveolar cavities. Since adequate terminology has not yet been coined for the description of the observed structures, the authors use the terminology of classical histology and from analogous descriptions of other reliefs. PMID- 2207735 TI - [Objective characterization of cough sounds]. AB - Objectification of the amplitude of the cough sound is important in determining its physiological or pathological nature. To achieve this aim an assembly for computer analysis in the time and frequency region was tested in an attempt to substitute the special equipment used at present by less expensive and readily available computer technique. At the same time the possibilities were assessed for using some statistical characteristics as diagnostic parameters in determining pathological changes of the cough sound. The physiological sound of cough was found to yield a hyperbola connecting the peaks of the individual bars of the frequency histogram which in pathological cough was represented by a line descending from left to right. Thus the two types of cough can be objectively distinguished. PMID- 2207736 TI - [Biorhythms and disorders of heart rhythm]. AB - Several factors are involved in the development of derangements of the rhythm of the heart. The role of some of them in the genesis of arrhythmias has not been fully elucidated as yet. It is still an enigma why some individuals develop derangements of the heart rhythm while others fail to do so under apparently equal conditions. Information on the value of biorhythms and their relevance to the development and course of arrhythmias is scarce and even controversial. Insight into these relationships and elucidation of the rhythmic nature of derangements of heart rhythm could be of great value in their prevention and treatment as well as in the prevention of sudden death. PMID- 2207737 TI - [Primary adenocarcinoma of the esophagus]. AB - The presented analysis of a patient treated at the 1st Surgical Department of the Teaching Hospital in Bratislava meets the criteria for being classified as primary adenocarcinoma of the esophagus, whose characteristics are described in the paper. Primary adenocarcinomas of the esophagus occur rarely and constitute only about 0.5% of large series of esophageal malignancies. The tumor is not connected with the gastric mucosa, being separated from it by the normal mucosa of the esophagus, and it is not a metastasis. The patients suffer from late not marked dysphagia. The endoscopic and histologic findings are frequently misleading since the mucosa above the tumor is usually intact. PMID- 2207738 TI - [The life and work of Professor Zdenek Frankenberger, the founder and first head of the Institute of Histology and Embryology at the School of Medicine of Comenius University in Bratislava]. AB - The life and work of Prof. MUDr. Zdenek Frankenberger is presented with the main focus on the 16-year period of his activities in Slovakia. His contribution to the history of the Bratislava School of Medicine is great both with regard to his activities both as its founder and excellent teacher of generations of Slovak doctors. He was striving hard to establish the Institute of Histology and Embryology whose first head he became. He participated in the establishment and development also of other institutes of the School of Medicine. An analysis of his remarkable and voluminous scientific work displays the extent of his education, knowledge and interests. His studies covered a broad range of scientific problems in the field of histology, microscopic anatomy, embryology, comparative anatomy and anthropology. Yet he was engaged also in faunal studies and became a reknown expert in entomology. Prof. Frankenberger contributed considerably to the executive work of the Medical School and was its vice-dean and dean. PMID- 2207739 TI - [The occurrence and evidence of malignant intraocular tumors in Slovakia (1968 1985)]. AB - The paper presents a survey of the incidence of notified malignant intraocular tumors, code 190 of the International Classification of Diseases (ICD-9). It analyzes the incidence, aspecific incidence and mortality rate also according to the 4th subclass of code 190 (ICD-9), covering the territory of the Slovak Republic in the period from 1968-1985. The incidence of intraocular tumors over the period studied was found to be 8.2/100,000 inhabitants. The recorded data correspond to values given for other regions. PMID- 2207740 TI - Communication between the PC and laboratory instruments. AB - In this paper we describe communications between a personal computer and any instrument with a serial port for the purpose of collecting data or controlling equipment and a program for performing this task. From a user-defined file, the software reads the communication parameters: baud rate, data bits, stop bits and parity. The communication protocol is also read: echo, acknowledge and end-of transmission characters. The software can be used to determine the protocol, to check the integrity of the communications, and can form the basis of a program for more specific applications. PMID- 2207742 TI - Generating precise mechanical stimuli and recording chordotonal organ discharge patterns using a microcomputer. AB - A computer-controlled system for the investigation of the response properties of the tibio-femoral chordotonal organ in the locust is described. The computer is used to generate small amplitude sinusoidal movements of the tibia via a small servo-controlled motor. The resulting response recorded via a suction electrode is simultaneously detected, processed and stored on disk. Full constructional details for all hardware required are given. The software, developed for a BBC microcomputer, in addition to controlling all the hardware, has graphics and analysis routines enabling the operator to display and manipulate the stored data. PMID- 2207741 TI - The development of a high-order Taylor expansion solution to the chemical rate equation for the simulation of complex biochemical systems. AB - A numerical method for evaluating chemical rate equations is presented. This method was developed by expressing the system of coupled, first-degree, ordinary differential chemical rate equations as a single tensor equation. The tensorial rate equation is invariant in form for all reversible and irreversible reaction schemes that can be expressed as first- and second-order reaction steps, and can accommodate any number of reactive components. The tensor rate equation was manipulated to obtain a simple formula (in terms of rate constants and initial concentrations) for the power coefficients of the Taylor expansion of the chemical rate equation. The Taylor expansion formula was used to develop a FORTRAN algorithm for analysing the time development of chemical systems. A computational experiment was performed with a Michaelis-Menten scheme in which step size and expansion order (to the 100th term) were varied; the inclusion of high-order terms of the Taylor expansion was shown to reduce truncation and round off errors associated with Runge-Kutta methods and lead to increased computational efficiency. PMID- 2207743 TI - A C version of Fourier-derived affinity spectrum analysis (FASA) to resolve binding heterogeneity. AB - The computer program described in this paper facilitates resolution of binding affinity heterogeneity by transforming binding curve data (bound versus free) into affinity spectra (density versus affinity). The original program, written in FORTRAN, is extended and presented here in the language C. New applications include an ability to transform competition curves into affinity spectra and to evaluate the effects of sampling and experimental error on spectrum analysis. We propose that this program be incorporated in the routine evaluation of binding systems. PMID- 2207744 TI - A knowledge-based experimental design system for nucleic acid engineering. AB - Presented in this paper is a knowledge-based experimental design system that incorporates the domain expertise used in nucleic acid engineering, thus automating the processing of error-prone, laborious low-level work, and many decision-making steps, and guiding the biologist toward a workable plan. This allows the biologist to work at a higher abstraction level, concentrating on more fundamental, difficult and challenging problems directly related to protein structure - function relationships. Cassette-based site-directed mutagenesis and synthetic gene designs are used as examples to illustrate the utility of the knowledge-based system approach to experimental design. PMID- 2207745 TI - A set of programs for analysis of kinetic and equilibrium data. AB - A program package that can be used for analysis of a wide range of kinetic and equilibrium data is described. The four programs were written in Turbo Pascal and run on PC, XT, AT and compatibles. The first of the programs allows the user to fit data with 16 predefined and one user-defined function, using two different non-linear least-squares procedures. Two additional programs are used to test both the evaluation of model functions and the least-squares fits. One of these programs uses two simple procedures to generate a Gaussian-distributed random variable that is used to simulate the experimental error of measurements. The last program simulates kinetics described by differential equations that cannot be solved analytically, using numerical integration. This program helps the user to judge the validity of steady-state assumptions or treatment of kinetic measurements as relaxations. PMID- 2207747 TI - MUCIDS: an operative C environment for acquisition and processing of polarized light scattered from biological specimens. AB - In this work, we describe a software package, MUCIDS, completely developed in our laboratory, for acquisition and processing of differential polarization light scattering data from specimens of biophysical interest. MUCIDS is a C environment that manages the whole activity of an instrument used for measurements of Mueller matrix scattering elements. It allows one to capture, analyse, process and display data from this or from other similar light-scattering experiments. The entire system is suitable for routine measurements in a general biophysical (or microbiological) laboratory because of its easy handling and maintenance. The software was written in C lattice and will run on IBM personal computers and similar. It uses IBM/DAC and GPIB/IBM interface cards. PMID- 2207746 TI - Quantitative analysis of the selective pressure exerted on homologous proteins. AB - Evolution analysis is used to locate the regions of a protein that are important for its function or structure. The rate of evolution is generally constant for a given family of homologous sequences. From the starting point of this observation, an algorithm is proposed to establish quantitatively the sequence zones where selective pressure is maximal. A program that computes this pressure has been written in PASCAL. Analysis of results on some sequences validate this theoretical approach, and this knowledge can be used as a starting-point for carrying out site-directed mutagenesis. PMID- 2207748 TI - Improved sensitivity of biological sequence database searches. AB - We have increased the sensitivity of DNA and protein sequence database searches by allowing similar but non-identical amino acids or nucleotides to match. In addition, one can match k-tuples or words instead of matching individual residues in order to speed the search. A matching matrix species which k-tuples match each other. The matching matrix can be calculated from a similarity matrix of amino acids and a threshold of similarity required for matching. This permits amino acid similarity matrices or replacement matrices (PAM matrices) to be used in the first step of a sequence comparison rather than in a secondary scoring phase. The concept of matching non-identical k-tuples also increases the power of DNA database searches. For example, a matrix that specifies that any 3-tuple in a DNA sequence can match any other 3-tuple encoding the same amino acid permits a DNA database search using a DNA query sequence for regions that would encode a similar amino acid sequence. PMID- 2207749 TI - An algorithm for searching restriction maps. AB - This paper presents an algorithm that searches a DNA restriction enzyme map for regions that approximately match a shorter 'probe' map. Both the map and the probe consist of a sequence of address-enzyme pairs denoting restriction sites, and the algorithm penalizes a potential match for undetected or missing sites and for discrepancies in the distance between adjacent sites. The algorithm was designed specifically for comparing relatively short DNA sequences with a long restriction map, a problem that will become increasing common as large physical maps are generated. The algorithm has been used to extract information from a restriction map of the entire Escherichia coli genome. PMID- 2207750 TI - Two- and three-dimensional image reconstructions from stained and autoradiographed histological sections. AB - A complete system has been developed to utilize histological serial sections for two- and three-dimensional image reconstructions. Eighty to 120 sections are digitized using a personal computing system augmented with a imaging board and CCD camera. The image files are transmitted to a VAX computer for processing and image reconstruction, and the processed images are transmitted back to the personal computer for display and recording using a film recorder or PostScript printer. The software developed for the system allows serial sections to be placed into proper registration in a 256(3) array, 256 grey levels. Autoradiographs of the sections are obtained in the presence of appropriate standards which are used to recalibrate grey levels to represent linearly the radioactivity of each pixel in the sections and scale the values to allow maximum use of the grey scale. Starting from coronally sectioned material the system has been used to analyse and reconstruct rat nasal turbinates. In two dimensions horizontal and sagittal sections have been obtained while in three dimensions back-to-front and surface-rendered images have been constructed. Useful rendering of differential metabolic activity within an organ of complex geometry has been obtained, and there appears to be no reason why the system cannot be used for any material for which serial sectioning is appropriate. PMID- 2207751 TI - POLCA, a library running in a modern environment, implements a protocol for averaging randomly oriented images. AB - The library POLCA implements the averaging of biological structures whose images are recorded in digital form from electron micrographs. The averaging protocol is based upon a method developed about ten years ago, which allows one to operate on a sequence of objects oriented and displaced at random within their frame; the relative rotations and the displacements of the structures are detected with the use of correlation algorithms and modified to make all objects appear the same, apart from their noisy components. The average image is then obtained by a simple addition and the signal-to-noise ratio is improved by a factor equal to the square root of the number of objects used to calculate the average. With respect to the original implementation of the method, two novel features characterize the library: the first one deals with the functions that are cross-correlated to determine the relative rotations of the structures; the functions used here are the inverse transforms of the amplitude spectra (IAS functions), which give rise to sharp maxima when they are cross-correlated. The second peculiarity is the systematic adoption, in the transformations of coordinates and in other circumstances, of an interpolation technique based upon the Fourier series kernel. POLCA is written in C and runs on a VME machine under the UNIX V/68 operating system. A programming style has been adopted to exploit fully the machine resources. PMID- 2207752 TI - Scrutineer: a computer program that flexibly seeks and describes motifs and profiles in protein sequence databases. AB - Scrutineer is an interactive, user-friendly program designed to search for motifs, patterns and profiles in the Swissprot, Protein Identification Resource (PIR) or SeqDb protein sequence databases. Basic capabilities include (i) searches for strings of amino acids with multiple choices at a given position; (ii) searches for strings including variable-length segments and delocalized constraints; (iii) searches over subsets of a database or particular regions within each sequence (e.g. N-terminal one-third); (iv) searches involving secondary structure predictions, physicochemical characteristics, and the like; and (v) searches using aligned sequences as targets with various optional weighting schemes. The various search criteria and hits can be combined and complex targets located. Once the data are loaded into virtual memory, all occurrences in PIR release 22.0 (3.7 x 10(6) amino acids) of a given short string of amino acids (e.g. a hexamer) are found in approximately 36 s. Scrutineer can also describe the entire database, user-specified hits, user-defined regions of sequence and all hits. The source code and accompanying manual are being freely distributed. PMID- 2207753 TI - Some programs useful for managing data in ecology, taxonomy and zoogeography. PMID- 2207754 TI - SUBSIS: DNASIS/PROSIS subdirectory management. PMID- 2207755 TI - STATSEARCH: a GCG-compatible program for assessing statistical significance during DNA and protein databank searches. AB - We describe a program STATSEARCH which implements the method of Mott et al. (1989) for searching DNA and protein sequence databanks for statistically significant similarities to a given query sequence. STATSEARCH is written to run in conjunction with the GCG sequence analysis package. PMID- 2207757 TI - Combination therapy with platinum and etoposide of brain metastases from breast carcinoma. AB - Twenty-two consecutive patients with brain metastases from breast carcinoma were treated with a combination of platinum (100 mg/m2 day 1) and etoposide (100 mg/m2 days 4, 6, 8) every three weeks. Five (23%) achieved a complete response (CR) while 7 (32%) obtained a partial response (PR) for an overall response rate of 55%. The 95% confidence interval for combined CR and PR was 34-76%. Five patients received brain irradiation after reaching the maximum degree of objective remission by chemotherapy. Median duration of combined CR plus PR was 40 weeks (12+; 152). Median duration of survival was 58 weeks (2; 208+). Fifty-five percent of the patients were alive at one year. Our study demonstrates that this combination treatment is highly effective in the management of brain metastases from breast carcinoma. PMID- 2207756 TI - Dose-dependent leucovorin efficacy with an intermittent high-dose 5-fluorouracil schedule. AB - Sixteen patients with metastatic carcinoma of the colon were treated with a regimen of leucovorin 200 mg/m2, given as a 10-min infusion followed by a median dose of 833 mg/m2 (range 500-1000 mg/m2) 5-fluorouracil every two weeks. For the 16 patients with proven metastatic disease, two-year survival exceeds 50%. Responses were: 2 complete; 4 partial; 4 minor; 3 progression; and 3 not evaluable but without progression to date. Toxicities include: 8 (50%) leukopenia; 9 (56%), 1 severe thrombocytopenia; 9 (56%), 2 severe, diarrhea; 9 (56%), 3 severe, nausea/vomiting; 8 (50%), 1 severe, stomatitis; 7 (44%) conjunctivitis; 6 (38%) alopecia; and 13 (81%), 3 severe, neurotoxicity. Leucovorin appears to exert a dose-dependent beneficial effect on both the response and survival produced by the intermittent high-dose 5-fluorouracil schedule. This benefit first appears to increase substantially when the leucovorin dose is increased from 120 to 200 mg/m2. Findings identify a testable candidate regimen for selected good risk patients. Full selection criteria remain to be identified. PMID- 2207758 TI - Platinol (CDDP) and continuous intravenous infusion 5-fluorouracil in refractory stage IV breast cancer: a phase II study. AB - Twenty-four patients with refractory Stage IV breast cancer were treated with platinol (100 mg/m2 i.v. Day 1) and 5-fluorouracil (1000 mg/m2 as a continuous infusion over 24 h daily for 5 days). Objective responses occurred in 12 of 24 patients (50%). The median duration of response was 4.9 months. Platinol and 5 fluorouracil in combination are active agents in patients with refractory breast cancer, and clinical trials are warranted in previously untreated patients. PMID- 2207759 TI - Sequential methotrexate, 5-fluorouracil, and leucovorin in metastatic measurable colorectal cancer. Does it work? AB - Four single-arm trials using methotrexate (M), 5-fluorouracil (5FU), and leucovorin (L) were sequentially performed in metastatic measurable colorectal cancer using different dosing and timing schedules for the three drugs. A total of 99 patients were entered into the trials, 92 (49 men and 43 women) of whom were evaluable for response. Although the first trial appeared to have a 36% response rate, the overall response rate seen in the four trials was not higher than historical reports of 5FU alone. We could find no correlation with dose intensity or patient characteristics to account for the apparent good results of the first trial. It is our conclusion that MFL is not an active combination in colorectal cancer. After progressing to the fourth trial, four patients were placed on 5FU alone (supported by a grant from Lederle, Canada). This resulted in one response in a patient who had not responded to the three-drug combination and stable disease in two patients previously progressing. Although there are many reports of this combination working, the possibility is raised that M may be inhibitory to the combination despite the in vitro data. PMID- 2207760 TI - 5-Fluorouracil with folinic acid is not effective against metastatic adenocarcinoma of the lung. AB - Thirty patients with a diagnosis of metastatic adenocarcinoma of the lung were entered on a trial to evaluate the antitumor efficacy of 5-fluorouracil 370 mg/m2 daily for 5 days every four weeks in combination with folinic acid 200 mg/m2, 60 min prior to 5FU. All patients had a good performance status, bidimensionally measurable disease, and weight loss less than or equal to 5% of preillness weight. Of the 29 evaluable patients, only two (7%) had partial responses (95% confidence limits 1-24%). Eleven (38%) had stable disease and 16 (55%) progressed. The two responding patients survived 12 and 60+ weeks. The median survival of all evaluable patients was 25 weeks (range 7-60+) and that of the stable patients was 26 weeks. The principal toxicities observed were diarrhea and stomatitis. Myelosuppression was rarely dose limiting. In contrast to the results of treatment with 5FU and folinic acid in metastatic colorectal cancer and breast cancer, the results of treatment with this combination of agents have been much less encouraging in adenocarcinoma of the lung. PMID- 2207762 TI - Computed tomography versus chest radiography: impact on management of patients with lymphoma. AB - To assess the influence of computed tomography of the thorax (CTT) in management of patients with lymphoma, we compared results of CTT and chest radiography (CXR) for 42 patients (65 examinations) with Hodgkin's disease (HD) with 48 patients (57 examinations) with non-Hodgkin lymphoma (NHL). Six percent (7/122) of all CTs resulted in major changes in patient management (95% confidence interval = 2 12%). In four patients with HD, influential findings included of additional sites of lymphoma and clarification of x-ray results. In three patients with NHL (5%), management was altered as a result of identification of additional sites of lymphoma on CTT. Eleven percent of CTT examinations clarified equivocal CXR findings in NHL, and management was affected in two of these cases. Our findings suggest that CTT is valuable in clarifying equivocal CXR findings, and in staging or restaging patients for whom the detection of mediastinal adenopathy affect patient treatment. PMID- 2207763 TI - Alpha-transforming growth factorlike activities and bifunctional regulators of cell growth in human malignant neoplasms. AB - Multiple transforming growth factors (TGFs) capable of conferring the neoplastic phenotype on NRK-49F cells without the addition of any other exogenous growth factor in the soft agar assay, were purified from two human solid malignant neoplasms: a squamous lung carcinoma and a pectoral rhabdomyosarcoma. In both tumors, low-molecular-weight transforming activities (4000-6000) that were not potentiated by epidermal growth factor (EGF), competed for binding to the EGF receptor, possessed mitogenic activity on NRK fibroblasts arrested in serum deprived medium, and did not show inhibitory effects on DNA synthesis induced by EGF and insulin in NRK cells. Other TGFs with molecular weights 9000 to 48,000, were also found in the malignant tissues examined; these TGFs, were not potentiated by EGF, did not compete for binding to the EGF receptor, were not mitogenic for NRK cells, and acted as potent inhibitors of DNA synthesis induced by EGF and insulin in NRK cells. These results demonstrate that growth-promoting activities, and modulating agents that can act as either enhancers or inhibitors of cell proliferation, are present in neoplastic tissues of different embryologic origin and histologic type. PMID- 2207761 TI - The diagnostic validity of the serum tumor marker phosphohexose isomerase (PHI) in patients with gastrointestinal, kidney, and breast cancer. AB - The diagnostic validity of the glycolytic enzyme phosphohexose isomerase (PHI) as a serum tumor marker was evaluated. For this purpose the sensitivity of PHI was determined in 435 patients with histopathologically defined, malignant gastrointestinal, kidney, and mammary tumors prior to primary treatment. To assess the specificity, PHI serum activities were measured in 181 patients with benign diseases and disorders from an internal practice. In gastrointestinal and kidney cancer, PHI reached an overall diagnostic sensitivity of about 70%, and a specificity of 92% was obtained. Even in early stages without metastasis, elevated PHI serum levels were found in about 60% of the patients. In mammary cancer, however, a sensitivity of only 40% was observed. PHI activity can be measured without the need for highly technical skills and equipment, in a short time and at low cost. These data suggest that serum PHI can be a useful indicator in the preventive checkup of gastrointestinal and renal cancer in medical practice. PMID- 2207764 TI - Mechanisms of action and clinical uses of estramustine. PMID- 2207766 TI - Photodynamic therapy of skin and esophageal cancers. AB - We report on 27 patients with cutaneous and subcutaneous malignancies and 40 patients with esophageal tumors treated with photodynamic therapy (PDT). Of those patients treated for skin tumors, seven had basal cell, three squamous cell, three malignant melanoma, one liposarcoma, and twelve had breast cancers. One patient had Bowen's disease. Treatment was given either by surface radiation or interstitially. One month after treatment, 48 (67%) of the treatment sessions resulted in a complete response (no clinical evidence of tumor) and 19 (26%) resulted in a partial response (more than a 50% reduction in the number or size of tumors). Of the 15 patients evaluable 12 months after treatment, 31 treatment sessions were evaluated as complete response 1 month after therapy, 15 (48%) of which retained this status at 1 year posttreatment. Esophageal tumors were as follows: 19 adenocarcinomas, 19 squamous carcinomas, and 2 melanomas. Most patients were reendoscoped 2 to 3 days after PDT and repeat endoscopies were performed 1 month after PDT and as needed when symptoms recurred. The goal of therapy was to improve the patient's ability to swallow. At 1 month, the average length of all tumors decreased from 7.0 to 6.1 cm, and the average minimal diameter opening increased from 6 to 9 mm. Of the 35 patients who were evaluable 1 month after PDT, the average diet grade improved from 16 to 32 (i.e., improvement in food intake from a liquid to a soft diet). PMID- 2207765 TI - Radioantibodies for the diagnosis and treatment of cancer; radioimmunoimaging (RAI) and radioimmunotherapy (RAT). PMID- 2207767 TI - Aggressive phase multiple myeloma: a terminal anaplastic transformation resembling high-grade lymphoma. AB - The term "aggressive phase" has been applied in multiple myeloma to the development of rapidly enlarging extramedullary soft tissue masses or of bone marrow transformation with histologic features resembling high-grade or anaplastic lymphomas. One hundred and one patients who fulfilled this definition were identified in a review of the literature. Eighty-six patients had soft tissue or visceral involvement and 15 bone marrow involvement. The mean age at initial diagnosis of myeloma was 53 years, suggesting that the aggressive phase may be more likely to develop in younger patients. A disproportionate percentage of these patients have an IgA gammopathy. Following the onset of the aggressive phase, these patients have a rapidly fatal course, refractory to therapy, with a mean survival of less than 3.5 months. It is hypothesized that this aggressive phase represents part of the natural history of multiple myeloma, analogous to the terminal transformations associated with other relatively indolent myeloproliferative and lymphoproliferative disorders. Studies are reviewed supporting the proposition that the clinical and morphological changes associated with the aggressive phase result from a clonal evolution of the original malignant cell line and do not represent the development of an independent new neoplasm. PMID- 2207768 TI - Tumor markers: what is their role? PMID- 2207769 TI - Clinical utility of serum osteocalcin. PMID- 2207770 TI - First reports from unexplored seas: radiolabeled antibodies and cancer. PMID- 2207771 TI - Molecular probes in neuro-oncology: the future. PMID- 2207772 TI - The film-reporting session as a qualifying examination in diagnostic radiology. AB - To assess the value of a film-reporting session as a qualifying examination in radiology, 11 residents were allowed 1 hour to interpret and dictate reports on 20 test cases. Reports were marked by four examiners; two used a standardized marking scheme and two a simple pass or fail assessment. The marking schemes were compared and the scores were related to the level of training and performance on the American College of Radiology (ACR) practice examination. With pass or fail marking, there was 55% agreement between markers and poor correlation with the candidates' training level. There was 100% marker agreement using the standardized scheme and better correlation with the level of training. There was poor correlation with the ACR scores. Preliminary results suggest that a film reporting session with standardized marking is feasible and may be a useful addition to current evaluation methods in diagnostic radiology. PMID- 2207773 TI - Adult myelography with iohexol. AB - An open, multicenter trial of adult myelography was carried out at six centers in 117 patients with iohexol (Omnipaque) 240 mg I/ml and 300 mg I/ml to determine whether there was a difference in visualization or side-effects when a lumbar or cervical approach was used to visualize the areas where disease was suspected. One hundred and thirteen myelograms were analysable. In over 85% of the myelograms with a lumbar approach, visualization of the area injected was excellent or good. Just over half of these were obtained with the intention of visualizing primarily the cervical area, and in 93% of these visualization was good or excellent at that site. In 100% of the cervically injected myelograms, visualization was excellent in the cervical area. Areas more distant from the injections were well visualized in the majority of patients. There was no significant difference overall in visualization with either of the two concentrations of iohexol used. There were 59 side-effects, mostly mild in nature; 40 of them occurred in 50 patients receiving the higher concentration and 19 in 63 patients receiving the lower concentration. The most common side-effect was headache (23 patients). Nystagmus was the only severe side-effect and occurred in only one patient having cervical myelography. The patient made a complete recovery within 36 hours. PMID- 2207774 TI - Glomus of the choroid plexus: the normal spin-echo appearance on magnetic resonance imaging. AB - The glomus of the choroid plexus is located within the trigone of the lateral ventricles. The magnetic resonance images of the choroid plexus in 624 patients of all ages were reviewed and graded to determine the variation of the appearance of the glomus of the choroid plexus as seen on T2-weighted spin echo (SE). With the moderately T2-weighted SE sequences the intensity of the choroid plexus signal was equal to, or less than, that from deep cerebral grey matter in 76% of patients and greater than that from deep cerebral grey matter in 23%; in 1% of patients the glomus of the choroid plexus was "cyst-like". In all 100 patients studied with the heavily T2-weighted SE sequence the intensity of the choroid plexus signal was greater than that from the deep cerebral grey matter. The variation in the normal appearance of the glomus of the choroid plexus is consistent with known histologic changes described in the literature. The importance of recognizing the glomus of the choroid plexus and not mistaking it for other normal anatomical structures or diseases is evident. PMID- 2207775 TI - The radiologic and endoscopic investigation and etiologic classification of gastritis in children. AB - In 11 children the endoscopic criteria for gastritis were correlated with radiologic and pathological findings. An etiologic classification is proposed. The diagnoses included gastric involvement by Crohn's disease (five children), eosinophilic gastroenteritis (one), diffuse varioliform gastritis (two), erosive gastritis associated with Campylobacter pylori infection (two) and idiopathic erosive gastritis (one). Eight of the nine double-contrast barium studies and only one of the three single-contrast examinations correlated with the endoscopic and histologic findings. In 10 children the endoscopic results correlated well with the biopsy findings. PMID- 2207776 TI - A prospective study of 8413 asymptomatic women undergoing mammography. AB - The authors report a 1-year prospective study of 8413 asymptomatic women who underwent mammography. Of 221 patients who underwent biopsy with preoperative needle localization, 61 proved to have a malignant lesion. The positive predictive value of mammography was 0.22 for microcalcifications without a mass, 0.64 for microcalcifications within a circumscribed mass or with architectural distortion and 0.33 for circumscribed densities or architectural distortions without microcalcification. The positive predictive value for carcinoma is broken down into age groups. PMID- 2207777 TI - Destructive joint disease following replantation of digits of the hand. AB - Microsurgical techniques now often allow the repair of severed digits. After noticing destructive joint changes in a patient who underwent such repair, the authors examined the postoperative radiographs of 27 other patients who underwent repair of severed digits at the University Hospital, London, Ontario, between 1984 and 1987. They found five patients who were similarly affected. The mechanism of destruction is not known, but the authors believe that osteonecrosis plays a role or that the cause may be neurovascular. PMID- 2207778 TI - Detection of acute cholecystitis in children. AB - Hepatobiliary imaging has an established diagnostic role in adults with acute cholecystitis but is underutilized in children. The authors report two children with acute cholecystitis, whose condition was diagnosed with the aid of a 99m technetium-labeled iminodiacetic acid (IDA) derivative. The diagnosis was confirmed surgically. PMID- 2207779 TI - Graft pseudoaneurysm simulating desmoid tumor recurrence. AB - A desmoid tumor is a rare neoplasm of soft tissues and, although benign, is locally invasive and tends to recur. We report a case of suspected recurrence of a supraclavicular desmoid tumor that had been resected 2 years earlier. Computed tomography suggested the correct diagnosis of a pseudoaneurysm of a venous graft that had been placed during the resection. PMID- 2207780 TI - Computed tomography demonstration of subarachnoid-pleural fistula. AB - A persistent left pleural effusion caused diagnostic difficulty in a young girl, 2 years after a road accident had rendered her paraplegic. Eventually, after instillation of a contrast medium into the pleural fluid, computed tomography showed a fistulous communication between the subarachnoid and pleural spaces at the level in the dorsal spine where trauma had occurred. PMID- 2207781 TI - Posterior fossa epidermoid in a member of a kindred with von Hippel-Lindau disease. AB - The authors describe the case of a middle-aged member of a kindred with von Hippel-Lindau disease in whom a posterior fossa epidermoid developed. The epidermoid was initially thought to be a hemangioblastoma, a tumor to which those who have von Hippel-Lindau disease are predisposed. Radiologic investigations, especially magnetic resonance imaging, were useful in demonstrating the extra axial nature of the tumor and also in characterizing it as an epidermoid. PMID- 2207782 TI - Malignant sacrococcygeal teratoma in an adult. AB - The authors report the case of a 49-year-old man who had a sacrococcygeal teratoma. Computed tomography showed a mass containing calcification. Digital angiography showed hypervascularization of the lesion. Histologic examination of a transrectal biopsy performed during sigmoidoscopy revealed the lesion to be a malignant teratoma which was not resectable or amenable to treatment. PMID- 2207783 TI - Large calcified pleural-based mass in the left hemithorax. PMID- 2207784 TI - A practical ruler for measuring cardiac diameter. PMID- 2207785 TI - The Sterling-Winthrop Imaging Research Institute. PMID- 2207786 TI - Medicolegal encounters in Canadian radiology. AB - Canadian radiologists interacted with the Canadian Medical Protective Association (CMPA) on 455 occasions between January 1983 and December 1987. The authors have reviewed and categorized these encounters: 55% were a direct result of a lawsuit against an individual radiologist; 28% were initiated by a radiologist who was seeking advice from the CMPA; 7% were requests by the radiologists for help in dealing with a complaint before a provincial College of Physicians and Surgeons. The 55% of encounters resulting in lawsuits are analysed in detail. They fell into four major categories: diagnostic errors (40%); complications of radiologic procedures (33%); patient injuries in a department of radiology (7%); and miscellaneous (20%). In addition to the categorization of cases, the authors make some generalizations about the costs of lawsuits against radiologists in Canada and present some illustrative case histories. PMID- 2207787 TI - Interobserver variability in the interpretation of contrast venography, technetium-99m red blood cell venography and impedance plethysmography for deep vein thrombosis. AB - Contrast venography (CV) is the standard technique for diagnosing deep vein thrombosis (DVT). Newer noninvasive tests have also proven efficacious. However, there is a lack of data on the level of agreement among observers in their interpretation of the results of the various tests. After agreeing on well defined criteria, three experienced observers assessed, blindly, the results of tests performed over a 4-month period on 117 patients who were suspected clinically of having had a first episode of DVT. The kappa statistic was used to measure the level of agreement beyond chance for CV (69 patients), red blood cell venography (RBCV) (82 patients) and impedance plethysmography (76 patients). The results of CV were assigned to normal, abnormal or inadequate categories, and those of RBCV and IPG to normal, equivocal or abnormal categories. The kappa values for CV, RBCV and IPG ranged from 0.53 to 0.56, 0.42 to 0.56 and 0.90 to 0.91 respectively. Values greater than 0.75 represented excellent agreement beyond chance and those between 0.40 and 0.75 represented fair to good agreement. Excellent kappa values were obtained for IPG because interpretation of the results of this method is entirely objective. Although the values for CV and RBCV showed good to fair agreement, there was a greater degree of observer variation, despite the well-defined criteria, indicating the subjectivity of interpretation of these test results. It is concluded that the kappa statistic can be used to measure observer variation of the results of tests for diagnosing DVT and may serve as a quality control tool for studies in which more than one person interprets the results. PMID- 2207788 TI - Computed tomography of cardiac and pericardial tumors. AB - Computed tomography (CT) scans in 30 patients with neoplastic involvement of the heart and pericardium were retrospectively reviewed. Computed tomography was compared with echocardiography in three of four patients with large primary cardiac tumors and in three patients with metastatic pericardial disease. Computed tomography was superior to echocardiography in determining tumor extent and site of origin of a right atrial sarcoma, as well as in assessing tumor extent and presence of pulmonary arterial hypertension in a left atrial malignant fibrous histiocytoma and a left atrial myxoma. Pericardial effusions were detected by echocardiography in two out of three patients with metastatic pericardial disease, but the malignant nature of the effusion was not recognized; in all three cases CT showed nodular pericardial thickening. Of the 23 patients with evidence on CT of direct extension of anterior mediastinal masses, bronchogenic carcinoma or mesothelioma to the pericardium 21 had nodular pericardial thickening and 2 diffuse thickening; only 6 had pericardial effusion. We conclude that CT is useful in the characterization of large primary cardiac tumors that are incompletely visualized with echocardiography. Computed tomography is superior to echocardiography in assessing tumor involvement of the pericardium because pericardial effusions are often absent; CT is also superior in identifying nodular pericardial thickening. PMID- 2207789 TI - Magnetic resonance imaging of hydrostatic pulmonary edema in isolated dog lungs: comparison with computed tomography. AB - Magnetic resonance imaging (MRI) is considered inferior to computed tomography (CT) in the assessment of lung parenchyma, being hampered by low proton density, magnetic susceptibility effects, flow, and cardiac and respiratory motion. In this study the authors assessed the potential usefulness of MRI by comparing it with corresponding CT images of the lung in the absence of motion. They studied eight excised normal canine lung lobes inflated with oxygen before and after induction of pulmonary edema produced by intravascular infusion of saline at 30 cm H2O. T1, T2 and proton density weighted, 5-mm thick, gapped, multislice sequences were performed at 1.5 T. Magnetic resonance images were compared with corresponding 5-mm collimation CT scans at identical levels both before and after the induction of pulmonary edema. The MR and CT scans were assessed independently by two chest radiologists. In normal lung, there was equivalent visualization of vessels down to 1 mm and bronchi to 2 mm in diameter. T1 and proton density scans demonstrated lower spatial resolution but greater contrast than the corresponding CT images. In pulmonary edema both T1 and proton density sequences demonstrated peribronchial edema with greater contrast than CT. Air-space filling was equally well demonstrated by either technique. The authors conclude that, in motionless lung, MRI has lower spatial but greater contrast resolution than CT. It is potentially superior to CT in assessing focal and diffuse lung disease if cardiac and respiratory motion artifacts can be minimized or suppressed. PMID- 2207790 TI - Coronal computed tomography. AB - The authors describe a method of direct coronal computed tomography (CT) of the body for infants and children who are introduced onto the gantry in a lateral decubitus position transversely across the examination table. Scans are planned from a lateral scout view, with the number of coronal scans ranging from four to six. Images are more informative and detail is sharper than routine axial cuts with coronal reformations. This method is valuable in resolving complex problems related to disease adjacent to the diaphragm and can accurately demonstrate the extension and relation of lesions to neighboring structures. PMID- 2207791 TI - Transvaginal sonographic evaluation of the retrodisplaced uterus. AB - To determine the clinical value of transvaginal sonography in the assessment of retrodisplaced uteri, the authors reviewed, retrospectively, 500 consecutive transvaginal (TV) and transabdominal (TA) sonograms. Of the 494 patients examined, 27 had a retrodisplaced uterus. Transvaginal sonography was superior to TA sonography in 25 patients, providing improved visualization of the endometrial canal, myometrium, adnexa and cul-de-sac. In 7 of these 25 patients, the findings that suggested the diagnosis were only seen on TV scanning. These findings included intrauterine pregnancy (three patients), fluid collection in the cul-de sac (two patients), fluid collection in the endometrial canal (one patient) and an embedded intrauterine contraceptive device (one patient). The two techniques yielded the same information in two other patients. In no patient was TA sonography more informative than TV sonography. The authors, therefore, conclude that TV sonography is the procedure of choice in assessing a retrodisplaced uterus and that additional examination with TV sonography is advisable whenever a retrodisplaced uterus is suspected. PMID- 2207792 TI - Coexisting false aneurysms of the radial artery. AB - The authors describe what they believe is the first report in the radiology literature of two coexisting, adjacent false aneurysms of the radial artery. They occurred in a 33-year-old man who had had cannulation of the radial artery during the management of multiple injuries sustained in a motor vehicle accident. Radial artery aneurysms are uncommon. Definitive treatment of false aneurysms of the radial artery consists of surgical excision with ligation of the artery or, if obstruction is demonstrated preoperatively, end-to-end anastomosis of the artery. PMID- 2207794 TI - Pseudo-intracardiac air in a heart-lung transplant patient. AB - Air in the heart is a serious condition and may be life-threatening. It is usually of iatrogenic origin or the result of trauma. Computed tomography of a heart-lung transplant recipient who had unilateral hydropneumothorax revealed a mediastinal gas collection that appeared to be intracardiac. A follow-up study with intrapleural contrast medium revealed that the gas was not within but was actually between cardiac chambers. Consequently the gas collection mimicking intracardiac air was of no clinical importance. PMID- 2207793 TI - Post-traumatic fat embolism in the inferior vena cava. AB - Histologically, pulmonary fat embolism is seen in up to 97% of traumatized patients, yet almost all of them are asymptomatic. Although clinically significant, fat embolism syndrome is not common; it is a frequent cause of death when it does occur. The authors report the computed tomographic demonstration of fat embolism in the inferior vena cava of a patient who sustained multiple fractures. To their knowledge, no similar case has ever been described. PMID- 2207796 TI - Residents' corner. Answer to case of the month #4. Rounded atelectasis. PMID- 2207795 TI - Embolization of a catheter-related hepatic artery pseudoaneurysm after long-term biliary drainage. AB - Hemobilia is a frequent complication of percutaneous transhepatic biliary drainage, occurring most commonly at the time of initial catheter placement. The authors report on the angiographic diagnosis and embolization of a pseudoaneurysm of the right hepatic artery in a patient with hemobilia. This occurred after 2.5 years of catheter drainage for biliary obstruction due to malignant disease. Bleeding as a complication of biliary drainage can be the result of inadvertent placement of catheter side holes in the hepatic parenchyma, iatrogenic arterioportal and arteriohepatic venous shunts and pseudoaneurysms. This case report illustrates that hemobilia, even with long-term percutaneous transhepatic biliary drainage, may be associated with a radiologically treatable, drainage related vascular abnormality rather than simply diffuse hemorrhage from a friable tumor. PMID- 2207798 TI - A holder for local anesthetic bulbs. PMID- 2207797 TI - Resident's corner. Case of the month #5. Abdominal pain. PMID- 2207800 TI - Mothers with mental retardation who do or do not abuse or neglect their children. AB - Mothers with mental retardation with or without a history of child abuse and/or neglect were compared on a number of demographic variables. The reasons why children were or were not removed also were examined. The demographic comparisons showed that while those mothers with such a history generally had higher IQs, they were similar to the mothers without such a history. Twice as many of those with a history of abuse and/or neglect were married, lived independently, and had at least two children, one of which often had problems, in comparison to those without such a history. Examination of the reasons for child removal showed that removal occurred if the mother had a problem in addition to her retardation or if she was unwilling to attend and actively participate in a training program and/or did not have someone who could provide support. If a mother was willing and did attend training and had support, children were either not removed initially or were returned upon evidence that the mother was actively participating. In comparison to those mothers with a history of abuse and/or neglect, those without such a history functioned at a lower intellectual and functional level and were living with a relative who shared child-care responsibilities. PMID- 2207799 TI - Sexual abuse and exploitation of children and adults with mental retardation and other handicaps. AB - There is growing recognition that children, adolescents, and adults who are mentally retarded are particularly vulnerable to sexual abuse and exploitation and are in need of intervention services. These people are especially vulnerable due to ther often life-long dependence on caregivers, relatively powerless position in society, emotional and social insecurities, and lack of education regarding sexuality and sexual abuse. In addition the mental health functioning and emotional development of individuals who are mentally retarded are not well understood, and many professionals remain uneducated about their mental health needs. To work effectively with this population, mental health professionals and educators must be alert to what is known about the sexual abuse and exploitation of persons with mental retardation. Furthermore, they need to become educated about the rights of these persons to special legal protection from abuse and neglect and to appropriate and effective mental health interventions. The challenge for mental health professionals and educators is to protect persons who are mentally retarded from sexual abuse and exploitation, to provide appropriate psychotherapeutic interventions when abuse occurs, to respect their right to developmentally appropriate knowledge about sexuality and sexual abuse, and to allow for the fulfillment of their sexuality. PMID- 2207801 TI - Report decision-making patterns among mandated child abuse reporters. AB - The goal of this investigation was to examine whether reporting decisions could be described by a coherent process that was consistent across incidents of suspected abuse. Using case vignettes imbedded in a national mail survey of mandated reporters, we examined the relationship between a series of judgments about the cases described in the vignettes and reporting intentions. These judgments included seriousness of the incident; whether the incident should be labeled "abuse" or "neglect"; whether the law would require a report; and whether the child and, separately, the rest of the family would benefit from a report. These five abuse-relevant judgments were strongly related to each other and together accounted for a substantial amount of the variance in reporting intentions. The law's demands most closely related to reporting intentions; benefits of reports were least closely related. Varimax rotation of a factor analysis revealed two factors: The first included seriousness, the abuse label, and the law's requirements, along with reporting intentions. The two benefit judgments loaded on the second factor. There were small differences in reporting judgments and patterns as a function of type of abuse. The implications of these findings for mandated reporter behavior are discussed. PMID- 2207802 TI - Some factors influencing abusers' justification of their child abuse. AB - The interviews of abusive caretakers originally carried out by Kadushin and Martin (1981) were coded and subjected to statistical analyses to determine what aspects of the caretakers' situation and of their interaction with the abused child had contributed to their belief that their treatment of the youngster was justified or not. A multiple regression analysis employing scores on the various indices obtained from the sample of 73 interviews indicated that the abusers tended to believe their behavior was justified if they thought the child had been defiant and they themselves had been under considerable environmental stress. On the other hand, they generally regarded their action as less justified if they had lost their temper and had been experiencing emotional distress. The latter finding suggests, in accord with Berkowitz's analysis of emotional aggression, that some instances of child battering were impulsive reactions to a provocative event. Although major emphasis is given to the meaning of these findings for the theoretical analysis of aggression, implications for protective service practice are also indicated. PMID- 2207803 TI - Patterns of child sexual abuse knowledge among professionals. AB - To better understand knowledge and perceptions of child sexual abuse, a survey was conducted of 902 professionals attending child sexual abuse educational programs during 1986-1987. About half (50.8%) of the group reported seeing at least two child sexual abuse cases a month, while 20.5% reported seeing five or more. Almost half (48.9%) of the respondents reported previous formal training regarding child sexual abuse. Professionals were generally knowledgeable about child sexual abuse; however, at least 20% of the professionals were not knowledgeable about some items that are important in the identification of child sexual abuse and that might hamper the legal and medical investigation of a case. Those with formal training, more years of professional practice, and who see five or more victims per month answered more questions correctly, but the differences were not always statistically significant. Further training for both medical and non-medical professionals is needed to ensure appropriate care of child sexual abuse victims and to improve communication and coordination of efforts between professions. PMID- 2207804 TI - Differential adult symptomatology associated with three types of child abuse histories. AB - Using scales specifically developed for this purpose, the present study examined university women's retrospective reports of childhood sexual, physical, and psychological abuse as they related to three types of current psychosocial dysfunction. Multivariate analysis revealed that, as hypothesized, history of psychological abuse was uniquely associated with low self-esteem, physical abuse was linked to aggression toward others, and sexual abuse was specifically related to maladaptive sexual behavior. This analysis also indicated that although there were unique effects of each type of abuse, physical and emotional abuse were often present together--a combination associated with generalized psychosocial problems. PMID- 2207805 TI - Child abuse by adolescent caregivers. AB - The purpose of this analysis was to estimate the frequency and severity of child abuse committed by adolescents who were in nonparental caregiving roles. The sample was composed of cases in which either physical or sexual abuse was substantiated through child welfare investigation. The main comparisons were between adolescent and adult caregivers. While caregiver age did not appear to have a consistent effect on the occurrence of physical abuse, notable differences between adolescents and adults were found in the area of sexual abuse. Not only were adolescents observed to commit substantially more sexual abuse than older caregiver cohorts, but the sexual abuse they committed was more likely to involve intercourse and physical assault. These findings have implications for future research and practice. PMID- 2207806 TI - Migrants and maltreatment: comparative evidence from central register data. AB - This paper reports the results of a series of studies on the abuse and neglect of migrant farmworker children. These investigations were conducted between 1983 and 1985 in the states of New York, New Jersey, Pennsylvania, Florida, and Texas. Names of approximately 24,000 migrant children obtained from annual migrant education censuses were individually cross-referenced with the appropriate state data bases to determine if they had been involved in a confirmed incident of maltreatment. The information acquired was converted to incidence estimates that were contrasted with the rates for all children in the respective states and were decomposed to identify high-risk cohorts within the migrant population. One finding common to all five assessments was that migrant children were significantly more likely to be maltreated than other children, although these incidence rates varied appreciably from one state to another. The emphasis of this paper is on the unique methodology employed in the research, issues pertaining to provisions for accessing central registers and protecting confidentiality of subjects, the generalizability of the findings, and cross state incidence differentials for both migrants and children from nonmigrant families. PMID- 2207807 TI - A multidimensional model for treatment of child abuse: a framework for cooperation. AB - This article presents a model of child abuse treatment that allows practitioners to consider in a systematic way the problems that arise when different agencies need to work together on complex child abuse cases. The paper proposes five stages through which such cases routinely progress: interagency cross referral, joint case conference, allocation of treatment responsibilities, simultaneous treatment, and formal joint periodic reassessment. It argues that the problems at these five stages are major contributors to treatment breakdown. The clinician who analyzes the dynamics at each stage is better equipped to control the treatment process than the clinician who restricts his or her attention to dynamics that are occurring within one agency. PMID- 2207808 TI - An evaluation of a support group for parents who have a sexually abused child. AB - This study investigates the effectiveness of a parent support group for parents who have a child who has been sexually abused. The parents completed pre- and post-evaluation packages to assess the effectiveness of the group. The Louisville Behavior Checklist, the Parenting Stress Index, and a subjective evaluation using a rating scale and content analysis were used. The results indicated that there were significant decreases in some of the children's dysfunctional behaviors, and the parents found the group helpful and rated it highly stating that they learned coping skills and felt more confident as parents. The parents' stress levels did not change significantly. The implications of the results and suggestions for further research are discussed. PMID- 2207810 TI - Professionals' attributions of censure in father-daughter incest. AB - Despite the recent increase in interest in the area of child sexual abuse, few studies have explored the attitudes of professionals involved in working with children. The present study investigates variables relating to the attribution of censure by two professional groups (teachers and social workers), to a victim of father-daughter incest, the father, and nonparticipating mother. Subjects were given one of four brief histories of a 14-year-old girl who had been sexually abused by her father. Cases varied according to whether the child had/had not resisted her father's advances and whether she had/had not had other sexual experiences. Subjects then completed a questionnaire and indicated the extent to which they attributed censure to the child, her mother, and father, and the extent to which they believed she would be affected by her experiences. Results showed that responses were influenced by the level of resistance, other sexual experiences, and respondents' sex and occupation. PMID- 2207809 TI - Determinants of placement for sexually abused children. AB - While conducting a prospective study of 100 sexually abused children, we found a much higher rate of out-of-home placement than has been previously described for child maltreatment. This study was designed to determine which factors were most influential in predicting the placement experiences of this cohort. The children, ages 6-17 years, were recently substantiated victims of intrafamilial sexual abuse whose parents or guardians permitted study involvement. We examined child and family demographics, abuse characteristics, and family response as possible determinants of immediate and later placement. At the initial assessment, within a few weeks of the disclosure, 50% of the children had already been removed. A follow-up assessment of 83 children two years later revealed that 73% had been removed from the abusing home. In a multivariate regression model, only maternal support of the child emerged as a significant predictor of immediate placement and placement over time. The offender's status as a resident in the child's home was an important predictor of immediate placement but was not significant as a predictor of all placements at any time. As maternal support is an important predictor of the need for placement, workers are encouraged to seek ways of enhancing maternal support as a means of reducing placement. PMID- 2207811 TI - Psychological profile of the female adolescent incest victim. AB - This research describes the personality and self-concept of the female adolescent incest victim. Subjects were 40 female adolescent incest victims, ages 12 to 18. Each adolescent completed the High School Personality Questionnaire, the Piers Harris Children's Self-Concept Scale, and a brief demographic questionnaire. These incest victims were shy, expedient, guilt-prone, aggressive, realistic, and withdrawn with low drive. Low overall self-concept with less happiness and satisfaction was characteristic. These adolescents also showed more confidence about physical appearance and intellectual and school status than other aspects of self-concept. The psychological profiles of these adolescents show they had accommodated to the abuse and suggest the beginning of an orientation of learned helplessness. PMID- 2207812 TI - Symptom differences in acute and chronic presentation of childhood post-traumatic stress disorder. AB - The authors report on 24 children diagnosed with post-traumatic stress disorder (PTSD) according to DSM-III criteria. Each child was designated as presenting with acute or chronic PTSD depending upon the duration of symptoms. Children with the acute form of PTSD presented with a relative increase in spontaneously acting as though the trauma were recurring upon real or symbolic exposure, difficulty falling asleep, hypervigilance, nightmares, exaggerated startle response, and generalized anxiety/agitation. Those presenting with the chronic form had relative increases in symptoms of detachment, restricted range of affect, dissociative episodes, sadness, and a belief that life will be too hard. PMID- 2207813 TI - Victims and perpetrators of sexual abuse: a psychosocial study from France. PMID- 2207814 TI - Child abuse and neglect in Brazil: after the congress. PMID- 2207815 TI - Genital warts in children. PMID- 2207816 TI - Improve your children .... change yourself! PMID- 2207817 TI - Manic depression: a pendulum of elation and misery. PMID- 2207818 TI - What the doctor says: asthma. PMID- 2207820 TI - The need to write. PMID- 2207819 TI - AIDS and Christian response. PMID- 2207821 TI - [Spina bifida: a terrain favorable to allergy to latex and to ethylene oxide]. PMID- 2207822 TI - [The physiopathology and medical treatment of acute traumatic occlusion of the popliteal artery. The point of view of the anesthesiologist-resuscitator]. AB - The acute occlusion of the popliteal artery involves: 1. A regional disease: muscular ischaemia with an increase of capillary permeability and oedema. The recovery of the circulation brings with it the formation of free radicals. 2. Sometimes, a general and metabolic illness complicates the muscular ischaemia. It associates to varying degrees: hypovolemic shock, metabolic troubles, acute renal failure, disseminated intravascular coagulation, infection. It can compromise the vital prognosis. The reanimation which completes the surgical treatment includes two stages: 1. The prehospital stage when the first imperative is to commit the patient to the vascular surgeon's care as soon as possible and in the best hemodynamic conditions. 2. The hospital stage when the therapeutic objectives are represented by: a) the treatment of hypovolemia; b) the curing of acute renal failure (bicarbonates 2 mmol.kg-1, hypertonic mannitol 1 g.kg-1; c) fight against infection; d) Heparin: 1 to 2 mg.kg-1 (if there is no counterindication); e) hyperbaric oxygen treatment in some situations. Despite the progress of reanimation, the initially intended amputation is subject to discussion in the following circumstances: crushing which in fact accomplishes an amputation, prolonged and complete ischemia lasting more than 10 to 12 hours, severe I.V.D.C., associated serious lesions (cranial traumatism, pelvis crushing). PMID- 2207823 TI - [The clinical use of atracurium in a developing country]. PMID- 2207824 TI - [Anesthesia for cardioversion. A comparison of propofol and etomidate]. AB - Anaesthesia for elective direct current cardioversion (DCC) was induced with propofol (Diprivan) 1.2 mg/kg in 28 patients and with 0.2 mg/kg etomidate (Hypnomidate) in 20 patients. These mostly high risk patients (NYHA class II to III) were successfully treated with defibrillation. Blood pressure and heart rate were recorded before and after induction and at 2 minutes intervals up to 20 minutes after DCC. Both anaesthetic agents caused mild hypotension. Heart rate did not change significantly after induction but fell significantly after DCC from the mean value of 124 +/- 26 bpm and 122 +/- 37 bpm to 94 +/- 19 bpm and to 91 +/- 19 bpm in propofol and etomidate treated patients respectively. Four patients became apnoeic necessitating assisted ventilation for approximately four minutes. All propofol treated patients had rapid recovery times and opened eyes on command within 5.6 +/- 1.9 minutes after induction, and were fully orientated about 4 minutes later also. Complete amnesia was observed in all patients in this group. In contrast etomidate induced anaesthesia did not cause respiratory depression, but the recovery time was longer. Four patients of this group complained of recall of DCC. In 7 patients due to involuntary movements or myoclonus, after induction with etomidate reliable EKG monitoring appeared to be difficult. PMID- 2207825 TI - [Peridural anesthesia for all women in labor: utopia or reality?]. AB - Peridural anesthesia in obstetrics is more and more widely used, improving comfort and security for delivery. In 1989, 74% of the deliveries occurred under peridural anesthesia in our unit. In order to assess if this percentage can be increased, we analysed during one month the reasons why some women did not get a peridural anesthesia. PMID- 2207826 TI - [The effect of effervescent cimetidine as premedication on gastric acidity during elective cesareans]. PMID- 2207827 TI - [The determination of ketamine in biological fluids]. AB - A method for the identification and quantification of ketamine in biological fluids by GC/NPD is presented. The procedure employs SKF 525 A as the internal standard and requires no derivatization. After a single-step extraction, analysis is achieved in 5 min. The lower limit of detection was found to be 1 microgram/1 for ketamine in plasma. This method appears to be rapid, sensitive and applicable to forensic and clinical toxicological analyses. PMID- 2207828 TI - [Differential clinical diagnosis of malignant hyperthermia]. PMID- 2207829 TI - [Medical informatics: the legal protection of programs]. PMID- 2207830 TI - [Malignant lymphomas and AIDS. Apropos of a case]. PMID- 2207831 TI - [Survival after a fat embolism in an only lung. Apropos of a case]. PMID- 2207832 TI - [Subendocardial and peridural ischemia in a healthy subject]. PMID- 2207833 TI - [Ethical aspects of animal experimentation]. PMID- 2207835 TI - [Recent developments in the European Foundation for Training in Anesthesiology]. PMID- 2207834 TI - [Validity of alternatives to animal experimentation in biomedical research]. AB - The "Three Rs" definition of alternatives by Russel and Burch (1959) refers to all methods, protocols, or technologies which replace the use of animals altogether, reduce the number of animals required, or refine existing procedures or technologies so as to minimize the level of stress endured by the animal. The move towards alternative methods in biomedical research must be seen as a gradual and evolutionary process during which each candidate method must be considered in a sequence of three consecutive steps, i.e., development of the test protocol, validation of its scientific merits and evaluation of its applicability to problems arising in practice. The validity of alternative methods is discussed in relation to the new legislation on animal experimentation and validation schemes already published. PMID- 2207836 TI - [Exercise ORSEC (Organization de la Securite Civile) and catastrophic medicine 1989. Tournus, Saone-et-Loire]. PMID- 2207838 TI - Positional cues and differential gene expression in somatic embryos of higher plants. AB - Much of the organization of higher vascular plants is determined during the formation of the embryo. In addition to the zygotic embryo which results from sexual fertilization in the ovule, many plants are capable of producing embryos from somatic cells. Of particular interest to plant developmental biologists is the phenomenon of somatic embryogenesis in cultures of the domesticated carrot which, because of its tractable nature in experimental manipulations, is presently regarded as a suitable model for studying pattern formation in plants. This short review considers the state of our knowledge concerning the origin and perception of positional information in plant embryos, and the temporal and spatial expression of genes. The available data provide a number of promising leads for cell-cell interactions in embryos, and there are some clear indications that the spatial distribution of certain gene products is correlated with changes in morphology. However, there is, as yet, insufficient evidence with which to forge a link between positional cues and the expression of genes which influence developmental transitions in embryos. PMID- 2207837 TI - [Posology of propofol as a function of age in pediatric ORL anesthesia]. PMID- 2207839 TI - Chick oviduct differentiation. The effect of estrogen and progesterone on the expression of progesterone receptor. AB - Progesterone receptor (PR) is a marker of estrogen action. Its cellular appearance during estrogen (20 mg/kg i.m.)-induced differentiation of the immature chick oviduct was therefore studied by immunohistochemistry. PR was located in the epithelial, mesothelial, submucosal stromal and smooth muscle cells. Progesterone (20 mg/kg i.m.) caused an obvious decrease in PR immunoreactivity without inducing synthesis of progesterone-dependent avidin. Thus mere receptor occupation by ligand is not sufficient for this induction. This paper reports that the expression of PR in the mucosal stromal cell differs from that in other cell types. In the mucosal stromal cell PR was inducible, i.e., not shown without the action of estrogen. The formation of tubular glands did not commence before mucosal stromal cells expressed PR. It would seem that the mucosal stromal cells have a crucial role in mediating epithelial differentiation. The onset of differentiation was preceded by vascularization and invasion of mononuclear cells in the submucosa. It was conspicuous that the smooth muscle cells of arteries also contained PR. PMID- 2207840 TI - [Complete bridge on osseointegrated fixtures avoiding a temporary complete denture]. AB - The possibility of placing fixtures between periodontically compromised teeth enables the immediate conversion from a fixed prosthesis supported by natural abutments to a temporary one supported by osseo-integrated fixtures. During the second surgical stage, the bridge on natural teeth is removed, the abutments are placed on the osseo-integrated fixtures and a new temporary bridge is prepared out of acrylic resin and gold cylinders screwed on the titanium abutments after the extraction of the residual teeth. The temporary bridge is realised for one side of the arc and then the other in order to control at all time the occlusion as well as the cosmetic aspect of the bridge. This approach avoids the passage by a mobile denture, shortens the healing period from 18 to 6 months and enables the prosthodentist to foresee the potential problems with the permanent fixed prosthesis. PMID- 2207841 TI - [Slip casting: design and processing]. AB - With the "In-Ceram" system ceramic constructions are made without any metallic support. The cosmetic ceramic (Vitadur N) is reinforced by an aluminous oxide framework made with a bio-ceramic containing 85% aluminium. The nature of this bio-ceramic and its use provide the originality of this procedure. In order to make this framework, a replica in special porous plaster is made based on the working model. This replica is plunged into a "barbotine" (aluminous oxide grains in suspension in water) which is deposited on the surface. After modeling this paste with a brush, the totality is dehydrated and brought to 1, 100 degrees C for 2 h without. This still fragile calcination is infiltrated by coloured glass. This second thermal treatment is carried out, after dehydration, at 1,080 degrees for 2 to 4 h, still vacuum. The second heating allows the calcination to become coloured and fill in the porosities. The conventional feldspar ceramic is then placed onto this very resistant (more than 580 MPa flexural strength) and exceptionally well adapted framework. This procedure is remarkable regarding the marginal adaptation, the quality of the aesthetic result, its biocompatibility and its ease in positioning. Moreover, the minimal thickness of the aluminium coping is 4/10 mm on the lingual and 3/10 mm for other sides, which therefore do not require any more laboratory work than what is required for making a ceramo metallic crown. Clinical follow-up over four years allows it to be stated that the mechanical and aesthetic qualities of the procedure permit the making of: single anterior and posterior units which can be made splinted; anterior maxillary small bridges (3 or 4 units) under normal occlusal conditions; posterior small bridges, under favourable occlusal conditions. PMID- 2207842 TI - [Fixed partial denture on osseointegrated screw implants]. AB - There are many differences between full dentures on Branemark implants and fixed partial dentures built on the same type of implants: due to some more critical anatomical conditions, the choice of number, position and length of the implants is more delicate; the need of an harmonious crown-gingival tissue relationship; higher occlusal forces than in edentalous cases; difficulty in satisfying aesthetic requirements and ease of hygiene. The surgical treatment plan, a pre requesite to any surgery, permits to determine the length of implants, their number, their position, their long axis direction and the design of the surgical guide, which will indicate to the surgeon the location and the axis for drilling. If this axis is nearly parallel to the sagittal plane for mandibular implants, it will be angulated to that same plane for maxillary implants. In the latter cases, it is often necessary to use angulated transepithelial abutments in order to prevent the abutment screw from having an occlusal access. In order to perform the prosthetis, an impression should be taken with the transepithelial abutments. The final reconstruction can be preceded by a temporary prosthesis, then (or) transitory to await gingival stabilization and not overload the implant immediately after it has been connected with the abutment. The fixed partial denture can be secured with screws or cemented when it is of small size and it must satisfy the functional and aesthetic requirements of the patient. The choice of the material used on the occlusal surface is very important and varies depending on the case. Aesthetics should not be prevent an in easy hygiene. These objectives are not reached at the time the prosthesis is made but during the course of the surgical and prosthetic treatment. Single restorations are subjected to the rules pertaining to any fixed partial denture on implants, but have particular characteristics, such as the almost systematic elimination of the abutment and the absolute necessity of the correct placement of the implant. The single units are more easily subject to unscrewing for mechanical reasons. Although the use of implants is a valuable aid in cases of partial fixed restoration, it requires particular attention with regard to precision. PMID- 2207843 TI - [Statistical analysis of functional interrelations between anterior guidance and posterior determinants]. AB - During the last decade, the concept of an effective, even steep anterior guidance did evolve toward the description of a "kinder" or "softer" anterior guidance which, while ensuring the disclusion of the posterior teeth, leaves some anterior functional freedom. It then becomes necessary to determine more precisely the criteria for diagnosis, orthodontic treatment, prosthetic restoration of anterior functional surfaces. In order to reveal some functional agreement between an anterior and posterior guidance, the analysis of the functional morphology of antero-maxillar teeth in relation to their skeletal context was proposed, in a study of 33 cases, so as to correlate the condylar steepness measured by axiography. It should be noted that a decreasing gradient exists between the mean respective values of the functional slopes of the central incisors (S1 = 64.3 degrees), and lateral incisors (SF1 = 53.5 degrees) and the canine (Cf = 51.8 degrees). Although the cingular surface S1 does not appear to have any influence on the posterior guiding factor (r = 0.1), in fact the anterior functional surface which is stategic in mastication, is located on the occlusal surface of the palatol side (S2) of the antero-maxillary teeth. The correlation is significant (r = 0.325) when the anterior guidance (incisives and canines) is associated to the mean condylar value more than being correlated to the mean functional value of the central incisor alone. It thus appears logical that the functional modeling of the articular cavities be influenced by the overall anterior guidance and not by the single central incisor. It has also been possible to emphasise the influence of the orientation of the occlusal plane in the anterior functional relationship (r = 0.547); thus, the anterior guidance appears to have to be assessed over a "relative overall analysis": overall: meaning the overall anterior guidance, i.e. the six anterior maxillary teeth; relative: meaning measured in relation to the occlusal plane. This concept of relative overall analysis of the anterior guidance, developed using a simple computerised program, will allow the diagnosis and anterior prosthetic or orthodontic restoration to be facilitated. PMID- 2207844 TI - [Stress breaking saddle framework or stress breaking framework. 1. Principles]. AB - The treatment success of a removable partial denture is conditioned by the respect of the base structures, tooth abutments and hard and soft tissues. In order to achieve this goal, the prosthesis should be in accordance with the following fundamentals: tissue duality (STEIGER diagram); visco-elastic behaviour of the mucous membrane (TURK, KYDD, DALY, PICTON WILLS); JORES, LERICHE and POLICARD principles. The proposed prosthetic solution, the stress breaker framework allows the disconnexion between the saddle and the framework as well as between the different saddles. The originality of the concept is due to the particular design of the framework, which permits the disconnexion of the saddle. Due to its principle, the displacement of the saddle takes place only when mastication forces are applied on the prosthetic teeth. These movements stimulate the bony tissues. The clinical construction of a stress breaker framework can be adapted to all types of edentation, as well as to sub-total dentures. The clinical results shown that, after twelve years of experience, the stress breaker framework allows the preservation of the abutments as well as the conservation of osseo-mucous tissues (no need of rebase). Several experimental research investigations have been carried out. Work on trial banks have revealed that, compared with the semi-rigid framework, the stress breaker framework lays less stress on the abutment and provides a better base surface beneath the saddle. Other studies have dealt notably with the displacement of the saddle as well as with fatigue tests of the prosthetic system. These studies have led to the development of specific preformed systems. PMID- 2207846 TI - [An original rehabilitation method for the totally edentulous. 1. Primary impressions]. AB - Primary impressions in full dentures are too frequently considered of lesser importance. The method described in this article gives much credence to the precision of these impressions, the quality of which is largely guaranteed by the final success of the denture construction. Several steps are required: anatomical investigation of the area using a heavy silicone; making of personalized impression (PEP) with correction depending on the area and the clinical observation; primary impressions including impression of the physiological borders with an adapted silicone material; furthermore, pre-estimation of the intermaxillary relationships and recording of the lip line with a material designed for this purpose. Once this stage has been completed, the practitioner already has at his/her disposal particularly valuable information; the primary impressions with borders registration; approximative occlusal relationships; volume of the future denture and the lip line. Now, an individual tray can be made by the dental technician, which will be really adapted to the clinical case. PMID- 2207845 TI - [Fluorescence of dental porcelain: material and methods]. AB - Dental porcelain emits some fluorescence under the action of ultra-violet rays. This emission may be at the origin of errors in the choice of the colour of a crown. In order to study this fluorescence phenomenon, the following experimental protocol has been developed: 363.8 nm exciting radiation isolated from the emission by an Argon laser; Fluorescence emitted by the sample and dispersed via a spectrometer, protected by a stop-U.V. filter; Influx collected by a photomultiplier, then directed, after passage in a picoamperemeter, toward a mini computer programmed to print the spectra; Correction of the spectra by a tungsten lamp used at the 2,600 K colour temperature; Use of reference spectra. On the same graph, the sample spectra are represented in solid lines, while the spectrum of the enamel used as a reference is shown as a dotted line. The results show that: Enamel has a fluorescence spectrum which has the shape of a wide band, with a maximum of 450 nm (characteristic of a blue-green shade) and a slow decrease up to 680 nm. The enamel fluorescence does not depend on the colour of the tooth; Dentine has a distribution spectrum which is similar to that of enamel but is three times fuller; The spectra of the ceramic samples reveal: a wide band due to transition metals, fine lines due to rare earth (terbium and europium). When the saturation degree of the ceramic increases, its fluorescence colour varies due to the relative increase in the amplitude of the lines in relation to the bands. Thus, when the sample colour progresses from B1 to B4, its fluorescence colour becomes greener.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2207847 TI - Remembering Clarence. PMID- 2207848 TI - Youth suicide is often a cry for help. PMID- 2207849 TI - How nursing diagnosis has helped nursing education. PMID- 2207850 TI - Effects of sanguinarine and Sanguinaria extract on the microbiota associated with the oral cavity. PMID- 2207851 TI - New perspectives on Sanguinaria clinicals: individual toothpaste and oral rinse testing. AB - Clinical studies conducted since 1983 on oral care products containing sanguinaria extract have yielded a variety of results. A careful review of these trials suggests that the designs used to conduct many of these trials may have had affected the study outcomes. Review of these trials suggests that studies testing the efficacy of anti-plaque products exercise the following guidelines: 1) use parallel instead of crossover designs, 2) select appropriate study populations, 3) use sufficient numbers of subjects to ensure statistical power, 4) select appropriate controls, 5) ensure intra- or inter-rater reliability prior to the start of the study, and 6) use proper statistical methodology. This review was undertaken to provide perspective into the results of these early studies, and furnish the rationale for the planning of subsequent clinical testing of sanguinaria-containing products. PMID- 2207852 TI - Sanguinaria toothpaste and oral rinse regimen clinical efficacy in short- and long-term trials. AB - Short- and long-term testing of sanguinaria toothpaste and oral rinse used individually have yielded both positive and negative results. This review evaluates the results of a number of clinical trials testing the regimen use of sanguinaria products for periods ranging from 14 days to six months. Review of these trials establishes the clinical efficacy of the two products in combination. The regimen approach produces consistently positive reductions in plaque, gingival inflammation and bleeding parameters for up to six months with no adverse hard tissue effects and only one reversible adverse soft tissue effect observed among the 260 subjects tested. In addition, no adverse microbiological shifts in the normal oral flora were observed. PMID- 2207853 TI - The impact of chemotherapeutic agents on treatment planning. AB - In this article the impact of chemotherapeutic agents on planning therapy for patients with plaque associated problems are reviewed. For special patients such as those receiving systemic medications which cause xerostomia or gingival hyperplasia, topical antimicrobials are of value for utilizing chemotherapeutic agents to teach patients a "clean mouth endpoint". Once achieved, patients can use this as a goal to obtain without the use of an agent. Two mouthrinses have been clearly shown to be effective in reducing plaque and gingivitis; one contains chlorhexidine and the other essential oils. A third agent, sanguinarine, found in both a dentifrice and mouthrinse, appears to be effective when used as combined therapy and further studies of combined usage are warranted. PMID- 2207855 TI - The Sanguinaria story--an update and new perspectives (overview of the Toronto symposium). PMID- 2207854 TI - Safety of Sanguinaria extract as used in commercial toothpaste and oral rinse products. AB - This report represents the findings of an Expert Panel on the safety of Sanguinaria extract used in Viadent oral rinse and toothpaste products and represents an independent review of the Sanguinaria extract toxicologic data base. It is based on reviews and discussions of the data base by all members of the Expert Panel on Sanguinaria extract. The Panel concluded that the data base on Sanguinaria extract is substantial and indicates that Sanguinaria extract is safe in its present use in Viadent products based on a large margin of safety between levels of human exposure and levels found to produce minimum effect or to be without adverse effect in animals. The panel further concluded that published literature suggesting an association between human exposure to Sanguinaria extract and potential reproductive, cardiovascular, or ocular toxicity, or carcinogenicity is largely anecdotal, unfounded, and not corroborated by or consistent with the substantial data base that was subjected to peer review. PMID- 2207856 TI - The history, chemistry and pharmacokinetics of Sanguinaria extract. AB - Sanguinaria extract is a mixture of benzophenanthridine alkaloids derived from Sanguinaria canadensis L. (bloodroot). This mixture of alkaloids has a long history of use in tinctures and expectorants in pharmaceutical products. The purity of Sanguinaria extract is well defined. The chemistry and biochemistry of these alkaloids, including the dynamic equilibrium between acid and base forms, and pharmacokinetics of Sanguinaria extract shall be presented when this extract is incorporated into a dentifrice or oral rinse formulation. PMID- 2207857 TI - The ultimate smile. Dental aesthetics gives cupid a nudge. PMID- 2207858 TI - Divorce and support: when and why. PMID- 2207859 TI - Dental faculties: future shock. AB - Canadian faculties of dentistry are in an untenable position. The university imposes expectations of research and publications; the profession and the public expect that competent clinicians will be educated. Senior administrators continue to attempt the impossible with diminishing resources and inadequate funding. Until this apparent conflict is resolved, it is unlikely that either of these major responsibilities can or will be effectively fulfilled. PMID- 2207860 TI - Taxing consumption: the GST. PMID- 2207861 TI - Common complications seen with osseointegrated implants. PMID- 2207863 TI - Tisseel, a two component fibrin tissue sealant system: report of a trial involving anticoagulated dental patients. AB - There have been attempts since the early years of this century to produce a biocompatible, biodegradable tissue glue to aid in hemostasis and lessen the need for conventional sutures. In the early 1970s, Matras et al developed a glue to anastomose the severed ends of peripheral nerves, and which was the precursor of the product tested in this trial. Since that time, the product has gained wide acceptance in Europe, with applications in microvascular anastomosis, hemostasis of soft tissue defects, bone sealing and dural sealing. PMID- 2207862 TI - Quebec dental manpower and demand for dental care from 1985-1988. AB - The rapid growth in the number of practising dentists is a major concern of the dental profession in industrialized countries. Three surveys conducted in Quebec in 1971 (N = 1552), 1985 (N = 840) and 1988 (N = 1059) examined the growth in dental manpower and demand for dental care between 1985 and 1988 and made a comparison with the 1971-1985 period. On average, the yearly increase in the number of active dentists was 4.2 per cent between 1971 and 1985 whereas the yearly increase between 1985 and 1988 was only 2.5 per cent. The percentage of the population using dental services annually was 47 per cent in 1988, compared to 51 per cent in 1985. An age-specific comparison with the United States showed that the proportion of Quebec adults visiting the dentist within the last 12 months varied between 30 per cent and 63 per cent and that of the U.S. between 41 per cent and 61 per cent. Thus, as the number of active dentists continues to grow, albeit at a slower rate, the demand for dental care appears to have reached a plateau and has attained the American level for adults under 50 years of age. PMID- 2207864 TI - Localized juvenile periodontitis: a review of the literature. PMID- 2207865 TI - Mired in myths and misconceptions? PMID- 2207866 TI - Computers in nursing. Software directory 1990. PMID- 2207867 TI - A prospective comparison of 4% polyacrylamide (Orcolon) and 1% sodium hyaluronate (Healon) in cataract and intraocular lens implant surgery. AB - We performed a prospective randomized clinical trial of 4% polyacrylamide (Orcolon) and 1% sodium hyaluronate (Healon) in routine extracapsular cataract extraction with posterior chamber lens implantation or in secondary anterior chamber lens implantation. Seventy consecutive patients were enrolled. The viscoelastic agents were compared in four areas intraoperatively: ease of injection, ease of removal, clarity of field and ability to hold back ocular tissues. Healon was significantly superior to Orcolon in all four areas. Further evaluations were performed on the first day and at 2 weeks postoperatively. Measurements of intraocular pressure (IOP) by Goldmann applanation and evaluations of corneal edema, epithelial keratitis and anterior chamber cellular reaction were recorded. Multivariable statistical analysis revealed only one difference between the two groups: significantly more patients in the Orcolon group (eight cases) than in the Healon group (two cases) had an IOP of 21 mm Hg or greater on the first postoperative day. PMID- 2207868 TI - Comparison of prednisolone acetate and indomethacin for maintaining mydriasis during cataract surgery. AB - Preoperative topical nonsteroidal anti-inflammatory drugs such as flurbiprofen and indomethacin have been found to maintain mydriasis during cataract surgery. Steroidal anti-inflammatory drugs are commonly used to treat postoperative inflammation, but their effect on the maintenance of intraoperative mydriasis is unknown. Forty-six patients admitted for elective cataract surgery were randomly assigned to one of three treatment groups and received 1% prednisolone acetate, 1% indomethacin or artificial tears four times before surgery, in addition to standardized preoperative dilating drops and intraoperative epinephrine. Pupillary diameter was measured and the time interval noted five times during the surgery. During surgery the indomethacin group lost significantly less mydriasis than the control group. The mydriasis losses of the prednisolone acetate group were between those of the indomethacin and control groups, but these differences did not reach significance. We conclude that prednisolone acetate is less effective than indomethacin for maintaining mydriasis during cataract surgery. PMID- 2207869 TI - Effect of flurbiprofen on the maintenance of pupillary dilation during cataract surgery. AB - A randomized, double-blind clinical trial was performed to evaluate the effect of flurbiprofen sodium (0.03%), a potent prostaglandin inhibitor, on the maintenance of pupillary dilation during elective extracapsular cataract extraction. Intraoperative pupillary measurements were taken before incision, after lens extraction and following cortex aspiration. The treatment group demonstrated statistically significant maintenance of pupillary area at each stage and in total (p = 0.003). The results indicate that the inhibition of prostaglandin synthesis by flurbiprofen aids significantly in the maintenance of intraoperative pupillary dilation. PMID- 2207870 TI - Changing indications for penetrating keratoplasty in Vancouver, 1978-87. AB - Indications for penetrating keratoplasty (PK) were assessed by clinicopathological review of 659 corneal buttons submitted from 1978 to 1987 to the Ophthalmic Pathology Service in Vancouver. Leading indications for PK were bullous keratopathy (22.2%), keratoconus (17.1%), scarring with or without chronic inflammation (13.5%), graft failure (12.1%), scarring or active keratitis secondary to virus (9.0%) and Fuchs' dystrophy (8.3%). The principal factors responsible for graft failure were also judged by clinicopathological correlation. The authors compare their findings with those in other series. PMID- 2207871 TI - Is corneal deposition of antimalarial any indication of retinal toxicity? AB - Ninety-five percent of patients on chloroquine demonstrate corneal deposition of the drug with the pupil dilated; less than 10% of patients on hydroxychloroquine show any corneal changes when so examined. I describe one patient on chloroquine and two on hydroxychloroquine who demonstrated large amounts of corneal antimalarial drug, leading to the early diagnosis of definite retinopathy. Examination of the cornea with the pupil dilated may reveal the presence of retinal toxicity in some patients. PMID- 2207872 TI - The management of chalazion: a survey of Ontario ophthalmologists. AB - Owing to the variability and lack of standardization of chalazion management, a survey of Ontario ophthalmologists was undertaken. The results highlight what ophthalmologists consider to be problems in chalazion management and suggest that a chalazion operation should be treated with the same respect given any other operation. PMID- 2207873 TI - Sarcoidosis of the eyelid skin. AB - A 64-year-old white woman presented with nodular lesions on the arms and face, including both medial canthi and the left upper eyelid. Histopathological examination of the biopsied eyelid lesion and other facial lesions disclosed the presence of noncaseating granulomas strongly suggestive of sarcoidosis. No other evidence of ocular sarcoidosis was present. The patient had clinical, radiologic and laboratory findings consistent with a diagnosis of systemic sarcoidosis. Therapy with chloroquine phosphate led to regression of the cutaneous lesions. PMID- 2207874 TI - Acanthamoeba keratitis with two species of Acanthamoeba. AB - We describe a case of Acanthamoeba keratitis related to soft contact lens wear. The patient presented with a 3-week history of severe uniocular pain, radial stromal infiltrates and subepithelial infiltrates with no epithelial defect. Acanthamoeba was cultured from the corneal biopsy specimen, contact lens and lens case. The corneal biopsy culture grew both A. castellani and A. polyphaga as well as Escherichia coli. The patient was treated with topical dibromopropamidine isethionate (Brolene) drops, neomycin and polymyxin B drops and fortified gentamicin drops. Gradual clinical improvement ensued. PMID- 2207876 TI - Schizophrenia, genes, and the art of thought control. PMID- 2207875 TI - The impact of primary nursing in psychiatry: the development of primary nursing. PMID- 2207877 TI - Treating children. PMID- 2207878 TI - Working with female adolescent date-rape victims. PMID- 2207879 TI - Decade of the brain. PMID- 2207880 TI - Coordination of a multi-joint movement in normal humans and in patients with cerebellar dysfunction. AB - The contribution of the cerebellar cortex to coordination of a multi-joint throwing movement was studied by measuring various movement and EMG parameters while normal control subjects and patients with cerebellar cortical atrophy threw a ball at a target. Although patients did not throw as accurately as controls, several coordination measurements were normal in the patients. These included parameters used by us to assess elbow-wrist coordination and the coordination of hand opening with activation of more proximal arm muscles. Postural support for the movement at the shoulder was also normal in that the shoulder was not pushed backwards by the reaction forces resulting from the rapid forward acceleration of the forearm and hand. In contrast, however, patients were unable to coordinate the muscles so as to produce the same hand direction from trial to trial when throwing at the same target. In addition, EMG onset times were abnormal in the antagonist muscles relative to agonist EMG bursts and kinematic parameters of the movement. In conclusion, our patients with cerebellar cortical atrophy showed abnormalities in visual-motor coordination, in that they were unable to consistently produce the appropriate hand direction in response to a visual target. Agonist-antagonist relationships were also impaired. Other aspects of coordination, such as the relative timing of EMG onsets of agonist muscles, even when these were active at different joints, were normal. PMID- 2207881 TI - Manual tracking performance in patients with cerebellar incoordination: effects of mechanical loading. AB - Manual tracking performance was studied in five patients with cerebellar incoordination due to unilateral cerebellar hemisphere lesions. The subjects were required to track a target on an oscilloscope screen by moving a cursor controlled by flexion-extension movements of the wrist. In comparison to normal subjects, the cerebellar patients, using their clinically affected arm, demonstrated irregular tracking patterns with inappropriate accelerations and decelerations, numerous high velocity peaks of movement, and an increased time lag between the cursor and the target. The addition of a viscous load provided by feeding back wrist velocity to a torque motor coupled to the apparatus resulted in significant improvement in tracking performance and suppression of the high velocity peaks. Increasing elastic stiffness by feeding back wrist position or inertial load by adding weights to the hand did not improve performance on this task. It is proposed that a hypotonic cerebellar limb behaves like an underdamped mechanical system. The addition of viscous loads helps restore more normal damping during voluntary movements of the arm. PMID- 2207882 TI - [Environmental factors in the etiology of Parkinson's disease]. AB - We examined the role of the environment in the development of Parkinson's disease (PD). A group of 42 parkinsonians have been compared with a group of 84 matched controls. The epidemiological study (1987-1989) covered the territory of the Community Health Department of Valleyfield, in southern Quebec (Canada). Odds ratio adjusted for age and sex were calculated for seven environmental factors. A decreased risk for PD was associated with residence in rural areas (OR: 0.31; p less than or equal to 0.05) and residence near industry or mining (OR: 0.15; p less than or equal to 0.05). An increased risk for PD seems to be associated with occupational exposure to the three metals Mn, Fe and Al (OR: 2.28; p = 0.07) especially when the duration of exposure is longer than 30 years (OR: 13.64; p less than or equal to 0.05). Other environmental factors not found to be associated with PD were: pesticides manipulation, farm work, industrial work and well water consumption. PMID- 2207883 TI - Selective deficits in Alzheimer and parkinsonian dementia: visuospatial function. AB - Deficits in visuospatial cognition are frequently cited as an important component of the cognitive changes accompanying Parkinson's disease. To characterize possible differences between Parkinson's (PD) and Alzheimer's (AD) dementia, patients from both groups, matched for overall dementia severity, age and education, were contrasted neuropsychologically. Visuospatial tasks dissociated from memory, were significantly compromised in both patient groups. Differential impairment was evident on visuospatial abstraction and reasoning (Object Assembly), which was most deficient in PD. Visuospatial cognition associated with memory, classified both patient groups as impaired compared to controls, but AD patients demonstrated substantially lower performance levels than those with PD. Parkinsonian dementia thus appears to have some distinct features compared to Alzheimer's disease, which may indicate differences in underlying pathogenic mechanisms. PMID- 2207884 TI - Parkinsonism with neuroacanthocytosis. AB - Two patients with neuroacanthocytosis are described. One presented with parkinsonism and the other resembled diurnal dystonia of the Segawa type. Both patients responded well to dopaminomimetic therapy. A PET scan with fluorodopa revealed a nigrostriatal deficit in the first patient. PMID- 2207885 TI - Syncope in childhood: a case control clinical study of the familial tendency to faint. AB - We investigated the possibility of an inherited tendency to faint by studying 30 consecutively referred well children with vasodepressor or vasovagal syncope. The family history of each patient was reviewed for syncope and for 24 cases was compared with the family history of the child's best friend. None of the best friends had syncope. 27/30 cases and 8/24 best friends had at least one first degree relative with syncope (p less than 0.01). Of the 8 best friend controls with a parent or sibling with syncope, the mother was affected in 7; 4/7 of these mothers had first degree relative(s) with syncope. In 11/30 patients both a sibling and parent had syncope compared with 1/24 of control families (p less than .01). We conclude that there is an inherited tendency to faint since most children who faint have a first degree relative who faints, a useful fact in differential diagnosis. This inherited tendency may be multifactorial but requires an environmental stimulus for expression. PMID- 2207886 TI - The value of CT scans for children with headaches. AB - We studied the value of CT scans for all children referred because of headache to one secondary and one tertiary pediatric centre during a 1 year period. Of 117 children who were seen by the Pediatric Neurology Service, at the I.W.K. Children's Hospital, 4 had CT scans and only 1 of these was abnormal. The consultant Pediatrician saw 40 children because of headache. CT scans were done on 3 of these patients and all were normal. None of the children who had a clinical assessment alone had unrecognized neurological disease during 20 months of follow-up. Therefore only 1 of 157 children had significant intracranial pathology. We conclude that CT scans have a limited role in the management of children with headache. PMID- 2207887 TI - Add-on trial of clobazam in intractable adult epilepsy with plasma level correlations. AB - Clobazam, a novel benzodiazepine, was used as an add-on agent in 47 adult patients with intractable epilepsy and a variety of seizure types. A greater than 75% reduction in seizure frequency was observed in 42% (18) of the patients and a greater than 50% reduction in 65% (29) of the patients which was sustained over a mean follow-up period of 13.3 (+/- 5.6) months. Nine patients had to discontinue the drug due to minor adverse effects or increased seizures. Possible tolerance developed in 6 patients. Plasma levels of the active metabolite N desmethylclobazam were linearly related to dosage and appeared to correlate with both therapeutic and toxic responses. Clobazam appears to be a safe and effective add-on antiepileptic for a wide variety of seizure types in intractable epilepsy. PMID- 2207888 TI - Clobazam as an add-on drug in the treatment of refractory epilepsy of childhood. AB - We report the results of a double-blind cross-over study comparing clobazam and placebo in the treatment of refractory childhood epilepsy. Fifty-two percent of patients had greater than 50% reduction in their seizure frequency when taking the clobazam. During the placebo phase no patient recorded a greater than 50% reduction in seizure frequency. Sex, age, seizure type, intellect did not appear to differentiate clobazam responsive from nonresponsive patients. Only 2/21 patients had behavioral changes on the drug sufficiently severe to require the patient to drop out of the study prematurely. Drug interactions between clobazam and the other anticonvulsant medicines did not occur. PMID- 2207889 TI - Extracranial repair of cerebrospinal fluid rhinorrhea. AB - There has been a recent renewal of interest in the extracranial repair of cerebrospinal fluid rhinorrhea because of the relatively high morbidity associated with the transcranial approach. The authors describe an extracranial approach that involves packing of the sphenoid and ethmoid sinuses on the side of the CSF leak. A case of successful treatment of CSF rhinorrhea by this method is presented. The extracranial approach may be advantageous for the repair of CSF rhinorrhea and the authors advocate an increase in its utilization by neurosurgeons and otolaryngologists working as a team. PMID- 2207890 TI - Paraneoplastic encephalomyelitis and subacute dysautonomia due to an occult atypical carcinoid tumour of the lung. AB - A case of paraneoplastic encephalomyelitis and subacute pandysautonomia associated with an occult atypical carcinoid tumour of the lung is described. The main clinical features were lethargy, impaired memory, constipation, and orthostatic hypotension. Neurological investigation was unremarkable except for mononuclear pleocytosis and increased protein level in the cerebrospinal fluid (CSF). Tests of autonomic function revealed a low plasma norepinephrine level, a marked drop of blood pressure (BP) to vertical tilt and Valsalva maneuver, and a marked rise of BP to dilute norepinephrine infusion. A few days prior to death, the patient became hypothermic and had repeated episodes of respiratory arrest associated with transient atrioventricular block on the electrocardiogram (ECG). A polysomnographic study confirmed a sleep apnea syndrome. Autopsy revealed an atypical carcinoid tumour in one tracheobronchial lymph node, widespread lymphocytic infiltrates and loss of neurons in the cerebral, cerebellar and brainstem grey matter, the spinal cord and roots, and the paravertebral sympathetic ganglia as well as microglial and astrocytic proliferation in the central nervous system. PMID- 2207892 TI - Clinical recovery and sleep architecture degradation. AB - We achieved a unique and timely recording of cerebral activity in a 70 year old woman immediately pre- and post-stroke, while studying the effect of acute cerebral infarction on sleep-electroencephalogram (EEG) patterns. Normal patterns, except for increased wakefulness, were recorded during two pre-infarct polysomnograms. Immediately following cerebral infarction increased delta activity was recorded from the infarcted hemisphere only. Initially, REM sleep could not be recorded from either side; however, on the third post infarct day REM sleep returned. Background EEG levels from both hemispheres became progressively slower, flatter and simpler. In addition, sleep spindles and the distinctive saw-tooth wave forms of sleep almost disappeared. At one year post stroke sleep-EEG rhythm recordings from both hemispheres became more similar except for persisting delta activity from the left hemisphere. Unexpected deterioration of sleep-EEG pattern recordings from the undamaged hemisphere taken during the patient's clinical recovery remains unexplained. Serial sleep recording may facilitate the study of brain recovery, activity and reorganization following stroke. PMID- 2207891 TI - Primary CNS lymphoma: lymphomatous meningitis presenting as a cauda equina lesion in an AIDS patient. AB - Neurologic complications of the acquired immune deficiency syndrome (AIDS) most often present as brain dysfunction and/or a polyneuropathy. We describe a unique neurological problem of a woman with AIDS who presented with a cauda equina mass due to primary CNS lymphoma. She subsequently developed a fulminant lymphomatous meningitis and died. Although previously rare, primary spinal cord lymphoma is expected to be encountered more often with the current AIDS epidemic and may be difficult to distinguish from infectious mass lesions. PMID- 2207894 TI - Association between Alzheimer disease and amyotrophic lateral sclerosis? PMID- 2207893 TI - Fatal streptokinase-induced intracerebral haemorrhage in cerebral amyloid angiopathy. AB - A fatal intracerebral haemorrhage (ICH) associated with streptokinase (SK) treatment of an acute myocardial infarction is described. Autopsy examination showed a lobar ICH and severe cerebral amyloid angiopathy (CAA). The close temporal relationship between SK administration and intracranial haemorrhage, the absence of pretreatment risk factors for ICH, and the presence of CAA suggests that these are related phenomena. Accordingly: 1. There may be a synergistic relationship between CAA and intracranial haemorrhage induced by fibrinolytic agents; 2. Thrombolytic agents may induce more frequent than expected intracranial haemorrhage in conditions associated with a high incidence of CAA, notably old age and Alzheimer's disease; 3. A regional defect in haemostasis other than vessel fragility may contribute to the intracranial haemorrhagic predisposition of CAA; 4. Autopsy examination of cases of ICH is an essential part of the audit of clinical trials of fibrinolytic agents. PMID- 2207895 TI - Dr. McKenzie's year with Dr. Cushing. PMID- 2207896 TI - Long-term management of asthma. PMID- 2207897 TI - Hypertension and eating habits. PMID- 2207898 TI - Management of children with head trauma. PMID- 2207900 TI - Abortion: a right or a treatment? PMID- 2207899 TI - Traumatic exodontia. PMID- 2207901 TI - A sample argument. PMID- 2207902 TI - Leave me alone. PMID- 2207903 TI - Guidelines are essential for quality assurance in practice. PMID- 2207904 TI - Physicians' perception of personal risk of HIV infection and AIDS through occupational exposure. AB - Physicians' response to acquired immune deficiency syndrome (AIDS) is poorly understood and often attributed to fear of human immunodeficiency virus (HIV) infection through occupational exposure. We surveyed 268 physicians from three geographic regions in North American with different specialties and responsibilities for HIV-positive patients. An important difference was found between the published risk and the physicians' perceived risk of infection after a single occupational exposure. Almost half of the respondents stated that they feared contracting AIDS more than other diseases. The physicians who perceived themselves to be at high physical risk were more likely than the others to report that AIDS had changed the way they interact with their patients (r = 0.26, p less than 0.001). No relation was found between the perception of physical risk and the number of HIV-infected patients (r = -0.07, p = 0.15). However, the perception of social risk showed a small inverse correlation (r = -0.15, p less than 0.02), in which the physicians with more HIV-infected patients reported less concern about negative social consequences. The physicians who perceived themselves to be at high personal risk were more likely than the others to report that surgeons have the right to refuse patients who do not wish to undergo HIV antibody testing (r = -0.16, p less than 0.01 for physical risk; r = -0.29, p less than 0.001 for social risk). Multiple regression analyses indicated that physicians' perception of physical risk was not related to age or sex but was modestly related to income source. The perception of social risk was related to sex and income source. Physicians' perception of personal risk is a crucial, yet often unacknowledged, component of the fight against AIDS. Our findings suggest that lack of attention to this issue is seriously compromising initiatives designed to facilitate physician participation in AIDS care. PMID- 2207907 TI - Verotoxin-producing Escherichia coli in ground beef in Manitoba. PMID- 2207908 TI - Regression of atherosclerosis. PMID- 2207906 TI - Undiagnosed phenylketonuria in adult women: a hidden public health problem. PMID- 2207909 TI - Oka standoff a health care nightmare for native doctor. PMID- 2207905 TI - Hypercalcemia in infants presenting with apnea. AB - To our knowledge apnea in infants has not been associated with hypercalcemia. We describe seven hypercalcemic infants aged 2 days to 3 months who had presented with apnea; six of the seven were otherwise healthy. The apneic attacks were brief, and normal breathing was restored spontaneously or after tactile stimulation. The attacks stopped and the apnea monitoring was discontinued when the children were 1 month to 2 years of age. The only abnormal finding common to all of the patients was hypercalcemia. Idiopathic infantile hypercalcemia was diagnosed in six of the patients and familial benign hypercalcemia in one. Our findings suggest that determination of the plasma calcium level be included in the investigation of apnea in infancy. PMID- 2207910 TI - Oregon tackles the health care rationing issue. PMID- 2207911 TI - Public service careers heaven for some MDs, hell for others. PMID- 2207912 TI - The animal rights war. PMID- 2207913 TI - Detecting and treating dyslipoproteinemias. PMID- 2207914 TI - Azathioprine or azidothymidine? PMID- 2207915 TI - ISI Sci-Mate Software System not available. PMID- 2207916 TI - CMA's code of ethics. PMID- 2207917 TI - Structured abstracts of original research and review articles. PMID- 2207918 TI - Guidelines on ethical and legal considerations in anonymous unlinked HIV seroprevalence research. Federal Centre for AIDS Working Group on anonymous unlinked HIV seroprevalence. PMID- 2207919 TI - Guidelines for medical practice: 2. A possible strategy. AB - The recognition that much current medical practice is based on incomplete scientific evidence has led to calls for the generation of guidelines for optimal patterns of practice. These guidelines must be developed from a synthesis of existing scientific data ideally obtained from randomized clinical trials. However, at present we may have to rely on less satisfactory data and the views of experts in the field. The primary purpose of these initiatives must be to improve patient care. The Ontario Medical Association has made recommendations on how such guidelines should be produced, and in a recent survey a substantial majority of family physicians supported them. There is general agreement that the coordinating body should be independent of government and other interested parties. In addition, the medical profession must have the primary role, and a number of medical organizations should also be represented. We propose a possible structure for a group charged with developing guidelines for medical practice at a provincial level and on an experimental basis. Recommendations are made on its membership, function and relationship with other organizations. The identification and diffusion of justifiable, scientific practice patterns will help reduce waste of scarce resources, maintain the role of the profession as guardian of the quality of care and ultimately benefit the patient. PMID- 2207921 TI - Carbon monoxide levels in indoor tractor-pull events--Manitoba. PMID- 2207920 TI - Gastrointestinal function and structure in HIV-positive patients. AB - We examined 19 patients (17 men) with human immunodeficiency virus (HIV) infection and gastrointestinal symptoms to determine whether those symptoms were due to either a gastrointestinal tract infection or a defect in mucosal absorption because of an enteropathy. The erythrocyte folate and serum vitamin B12 levels were within normal limits in all of the patients. The serum ferritin level was elevated in 12. The xylose absorption test results were abnormal in 8 of the 13 patients able to complete the study. None of the duodenal aspirates yielded a pathogen. Light microscopy revealed nonspecific lymphocytic inflammation without infection in the stomach (in seven patients), the esophagus (in five), the duodenum (in two) and the rectum (in two). However, biopsy specimens were positive for Candida albicans in the esophagus (four patients), cytomegalovirus in the esophagus (one) and the rectum (two), Helicobacter pylori in the antrum (two), Treponema infection in the rectum (two) and Mycobacterium avium-intracellulare in the small intestine (one). Only three patients had a normal series of biopsy specimens. All of the patients had similar ultrastructural changes at the epithelial-stromal junction of the antral glands and in the intestinal crypts. We conclude that abnormal biochemical and endoscopic findings are common in HIV-positive patients with gastrointestinal symptoms. Defects in carbohydrate absorption and ultrastructural changes may be responsible for some aspects of HIV enteropathy. PMID- 2207922 TI - Tolerance for HIV patients goal of MD's book for children. PMID- 2207923 TI - Use discretion in treating HIV patients, FPs told. PMID- 2207924 TI - Damage awards to patients up 48% in 1989, CMPA reports. PMID- 2207925 TI - The Crashcart Companion. PMID- 2207926 TI - Searching for the lemming gene. PMID- 2207928 TI - Interest in alternative birthplaces among women in Ottawa-Carleton. PMID- 2207927 TI - Here's why nurses are quitting. PMID- 2207929 TI - Embolism during intrauterine laser surgery. PMID- 2207930 TI - My quest for eternal youth. PMID- 2207931 TI - Screening for congenital dislocation of the hip: an economic appraisal. PMID- 2207932 TI - Implications of the Canada youth and AIDS study for health care providers. PMID- 2207933 TI - Prevention of sexually transmitted diseases: whose responsibility? What message? PMID- 2207934 TI - Out-of-laboratory measurement of the blood cholesterol level. Canadian Society of Clinical Chemists Task Force on Out-of-Laboratory Blood Cholesterol Measurement. PMID- 2207935 TI - [Residents and the teaching role: review of the literature]. AB - We reviewed the available data on residents' teaching role in the clinical setting to develop programs to improve their teaching skills. Articles published from 1966 to 1989 were identified through a computerized search of MEDLINE, and the bibliographies of identified papers were reviewed. Articles directly related to the topic were included and analysed. Taking into account their quality, we extracted data relevant to specific issues. Approximately 15% to 25% of an average work week was spent by residents in different teaching activities. Students acknowledged the importance of their contribution to clinical teaching. Residents benefitted from teaching by increasing their medical knowledge and promoting the development of important attitudes. Insufficient preparation for this task and the numerous practical problems faced by residents may explain their modest performance as teachers. Nevertheless, programs directed to residents might improve the quality of their teaching. We suggest some guidelines for the development of programs to improve their teaching skills and for future research. PMID- 2207937 TI - Walk-in clinics: implications for family practice. AB - To understand better the reasons for the growth in popularity of walk-in clinics in Canada we surveyed 321 patients with a regular physician in Toronto who attended a walk-in clinic in the same city over a 16-day period in February 1988. They were asked their reason for attending the clinic, their perception of the urgency of their problem, their choices as alternatives to walk-in clinics and their satisfaction and concerns with the type of care received at the clinic. The three most common reasons for attending the clinic were convenient location (in 33% of the cases), inability to see their regular physician soon enough (in 16%) and no appointment needed (in 13%). Most (80%) of the patients felt that they needed medical attention within 24 hours after the onset of their problem. Most (83%) of the respondents would have sought medical attention at another walk-in clinic, from their regular physician or at an emergency department had the clinic been closed. Only 36% and 18% of the patients respectively responded that their regular physician worked evenings or weekends. Most of the visits to the clinic were outside regular weekday business hours. The level of satisfaction with the service received at the clinic was high. The extended hours and no-appointment philosophy of walk-in clinics, coupled with family physicians' reluctance to work evenings and weekends, have made such clinics an attractive option for patients with primary care problems that they believe require prompt attention. PMID- 2207936 TI - Iron status of very-low-birth-weight infants during the first 15 months of infancy. AB - The adequacy of iron stores in infants of very low birth weight (defined as less than 1500 g) in Canada is unknown. We monitored the iron status of 81 such infants at 3, 6, 9, 12 and 15 months of age. All of the infants were fed formula fortified with iron (13 mg/L) for at least 6 months, starting at 2 months of age. The plasma ferritin level decreased after the formula was no longer used. Although 90% of the infants were given cereal fortified with iron (30 mg of iron per 100 g) by 9 months of age, the plasma ferritin level continued to decrease. The level was less than 10 micrograms/L in 54% of the infants at 12 months of age and in 74% at 15 months; this indicated depleted iron stores. Because of delayed development very-low-birth-weight infants eat small amounts of cereal and therefore require iron-fortified formula throughout infancy. PMID- 2207938 TI - Porphyria cutanea tarda due to ferrous gluconate. PMID- 2207939 TI - Management of people exposed to pertussis and control of pertussis outbreaks. PMID- 2207940 TI - Canada's blood collection system should be reorganized, critics say. PMID- 2207941 TI - Military MDs used to peace prepare for war. PMID- 2207942 TI - Women close in on 50% share of places in Canada's medical schools. PMID- 2207943 TI - End of shift. PMID- 2207944 TI - With TIAs, MDs cannot rely on patients to provide a meaningful history. PMID- 2207945 TI - Occupational associations among British Columbia male cancer patients. AB - In a study of 6,389 male cancer patients diagnosed and treated at the Cancer Control Agency of British Columbia from 1950-1975, several associations were detected between occupation and specific cancers. Elevated risks for lung cancer were seen in miners, metal processors and machinists, while a reduced risk was seen in farmers. Lip cancer excesses were detected in individuals involved in several outdoor occupations, and melanoma excesses were seen for three groups of predominantly indoor workers. These results confirm previous findings in the literature, whereas the following associations have not been previously reported. Fishermen were found to have an excess of Hodgkin's Disease (RR = 3.0, 95% C.I. = 1.4,6.5), engineers are at an elevated risk of cancer of the pancreas (RR = 4.2, C.I. = 1.8,9.9), and forestry workers have an elevated risk of bladder cancer (RR = 1.7, C.I. = 1.1,2.6). Further studies will be needed to replicate the new associations detected here. PMID- 2207946 TI - Lead toxicity in the shipbreaking industry: the Ontario experience. AB - Lead exposure occurs during ship demolition when the ship structure has been previously coated with lead-based paint. An investigation and follow-up of employee lead exposure at the 4 shipbreaking operations in Southern Ontario revealed widespread excessive lead exposure. Air sampling results for lead were above the Ontario standard at all locations. 34 of 113 workers (30%) had at least one blood lead above 3.4 mumol/L*; 50% of workers at one company had results above 2.5 mumol/L. At these blood levels, neurologic, renal and hematologic effects may develop. Institution of control measures (appropriate respirators and hygiene practices, worker education and training, prompt employee notification of blood lead levels) reduced employee lead exposure and lowered blood lead results. Continued vigilance and ongoing employee education and training are required to prevent lead toxicity in shipbreaking. *70 micrograms/100 ml = 3.4 mumol/L. PMID- 2207947 TI - Pathogenic marine vibrio species in selected Nova Scotian recreational coastal waters. AB - Seven heavily frequented coastal recreation sites serving Metropolitan Halifax and Dartmouth were investigated to determine the numbers and species of pathogenic marine vibrios (PMV) present. Seawater, mussels and sea gull feces were cultured using quantitative methods and the effects of temperature and fecal pollution noted. Emergency rooms serving the sites under surveillance were monitored for PMV-related infections. All 11 recognized species of pathogenic marine vibrios were recovered from the 7 sites. Estuarine sites yielded a greater variety of species and greater numbers of PMV than non-estuarine sites. Culture of hand washings after immersion in seawater did not demonstrate contamination of skin by PMV. We did not demonstrate any cases of PMV infection associated with the 7 surveillance sites. PMV contamination of marine recreational waters does not frequently result in superficial infections. PMID- 2207948 TI - An outbreak of Campylobacter enteritis associated with a community water supply. AB - In June 1987, an outbreak of acute enteritis occurred over a period of 2 weeks in a small rural community where the potable water supply is unfiltrated and unchlorinated. Campylobacter jejuni was isolated from 6 patients. A case-control study performed in a local fiberglass shop where workers drink a lot of water, showed an association between the occurrence of enteritis and the consumption of 10 or more 8-ounce glasses of water per day (Odds Ratio = 6, p = 0.04). The attack rate of enteritis was 23.2% (13/56) in that industry where a dose response relationship was also noted (p = 0.05). C. jejuni was not recovered from the local water supply, which had temporarily been chlorinated the day before the samples were drawn. However, samples taken just before the outbreak showed high coliform counts. This episode suggests that unprotected water systems may be contaminated by C. jejuni. PMID- 2207950 TI - Toward the development of self-help health behaviour change programs: weight loss by correspondence. AB - The goal of this study was to evaluate a correspondence weight control program, and to assess the impact of three program elements (weekly homework, interim weigh-ins, and participation deposits) individually and in combination. All treated participants received 15 weekly standard lessons by mail. Three program features were varied factorially: a) homework assignments, b) interim weigh-ins and c) a deposit refunded contingent on returning homework and/or attending interim weigh-ins. Participants were assigned randomly to active treatment conditions or a delayed treatment control group. Among treated males (N = 14), initial average weight loss and BMI reduction were 9.6 kg and 3.1 respectively; average net weight loss and BMI reduction at one year follow-up were 5.8 kg and 1.9 respectively. Among treated females (N = 128), initial average weight loss and BMI reduction were 3.1 kg and 1.2 respectively; average net weight loss and BMI reduction at one year were 2.3 kg and .88 respectively. Women in all treated groups, except lessons only, showed a greater BMI reduction than untreated controls at the end of treatment. Women in conditions including both homework and interim weigh-ins had greater initial BMI reductions (M = 1.6) than those who received lessons only (M = .76). At one year, net BMI reductions were comparable across all treated groups. Of the 42 women initially registered in conditions that included both homework and weigh-ins, 12 who denied joining other programs lost at least 4.5 kg (M = 7.1) during treatment, and 7 had a net loss of at least 4.5 kg (M = 8.0) at one year without apparent involvement in any other program. PMID- 2207949 TI - Survey of methadone patients in Canada. AB - We present the results of a survey outlining the frequency of certain activities associated with drug-seeking behaviour, e.g. needle sharing, illicit activity. The data presented are based upon information concerning 1,000 patients receiving long-term Methadone as a treatment for opioid dependence. These data are unique in that specific information of this nature has never before been made available in Canada, and are of interest in view of the AIDS epidemic. PMID- 2207951 TI - Health warning labels for alcoholic beverages in Canada. AB - This paper reviews the background and rationale for health warning labels for alcoholic beverages. They have been recently approved for the United States. Mexico and Colombia already have such labels. However, Canadian health officials seem reluctant to require them unless the alcohol industry agrees. Arguments against labels (i.e. that they detract from other efforts, are misguided or ineffective) are not convincing. Evidence from research on health warnings on cigarettes and prescription and non-prescription drugs shows that labels can be effective if well designed. Special problems in having bilingual labels may exist but could be overcome. Canada should have health warning labels on alcoholic beverages as soon as possible. PMID- 2207952 TI - The impact of AIDS education among elementary school students. AB - We report the results of a controlled prospective study designed to assess the impact of education on AIDS among elementary school students. 1,825 students from 3 school boards participated; 848 students were assigned to the trial group and 778 to the comparison group. Overall, the results showed a significant increase in students' level of knowledge of AIDS following their classroom lessons on AIDS. The students exposed to AIDS education expressed more accurate and appropriate beliefs about the transmission of AIDS. The students' reports indicated that television and magazines were their main outside sources of information about AIDS. Generally, the students demonstrated a positive attitude toward the AIDS curriculum. We conclude that classroom education on AIDS is effective in imparting knowledge and changing students' beliefs about AIDS. Further periodic assessments of AIDS education programs would be required at a variety of educational levels to determine if this change will lead to alteration in behaviour. Such assessments would help in the development of more comprehensive and cohesive programs in AIDS education. PMID- 2207954 TI - Injection drug use and needle sharing among Ontario students. PMID- 2207953 TI - AIDS seminars for senior grades in secondary schools. AB - AIDS seminars lasting 70 minutes, consisting of an oral presentation, a videotape and time for discussion, were offered to students in grades 11, 12 and 13 in secondary schools in the Hamilton Board of Education. Specially chosen teacher and public health nurse facilitators were assigned to sessions. 19 secondary school principals and 1,898 students in 10 schools completed questionnaires about the usefulness of the seminars. Students and principals viewed the seminars. Students and principals viewed the seminar as highly valuable for obtaining new information in sessions with either public health nurse or teacher facilitators. The oral presentation was rated most valuable but students rated the videotape and the discussion components highly as well. The students strongly agreed that the seminar assisted in understanding how STDs could be prevented, and made them aware of the community groups or agencies they could go to for help. A substantially greater number of females than males indicated they wished to attend other seminars. PMID- 2207955 TI - Impact of HIV infection/AIDS on social service agencies serving children and youth in Toronto. AB - There are few data on how HIV infection/AIDS affects social service agencies serving children and youth. We conducted a survey of 24 provincially funded agencies in the Metro Toronto area and discovered that 36 clients and 9 staff members were HIV-infected. Our data strongly suggest that these agencies were ill equipped to cope with issues surrounding HIV infection/AIDS. Inadequacy or absence of policy and procedures resulted in confusion regarding issues such as HIV testing, need to know, confidentiality, duty to warn, staff and client education, and universal precautions for infection control. In order to effectively deal with the psychosocial, legal, ethical and education needs of clients and staff, agencies must be pro-active in developing policy and procedure. PMID- 2207957 TI - Re: Last JM. The failures of success. Can J Public Health 1990;81:91. PMID- 2207956 TI - Social and school factors in predicting cannabis use among Ontario high school students. AB - This paper explores the influence of social factors and school factors on cannabis use among Ontario high school students. The data are derived from a survey of students conducted by the Addiction Research Foundation in 1987. Multiple classification analysis was used to examine the relationship between the two groups of factors and cannabis use. Results of the analysis indicate that social factors are more highly predictive of cannabis use than are school factors. A theoretical framework specifying the influence of social and school factors on cannabis use needs to be developed and tested in order to understand this relationship more clearly. PMID- 2207958 TI - Identifying and helping alcohol abusers attending general health care services. AB - Studies conducted in Canada and elsewhere show a high prevalence of alcohol related problems among general practice patients, users of accident and emergency services, and patients in some community-based and hospital-based outpatient and residential settings. However, many users of general health care services with alcohol problems are not recognized as such. Also, even when identified, alcohol abusers are not always treated for alcohol abuse per se. Interest in prevention and in early identification of alcohol problems is also low among many health care professionals. Alcohol problems can be prevented and treated. Health care professionals should thus try to identify clients with alcohol-related problems and those at risk. These clients should then be provided with appropriate information and advice and, if necessary, referred to a specialized addiction service. The routine use of simple, structured questions concerning drinking will facilitate the identification process. PMID- 2207959 TI - A community-based health promotion project for persons with chronic respiratory disease. AB - Enhancing people's capacity to cope with chronic conditions is a growing challenge for community health professionals. I describe a community-based support group for persons with chronic respiratory disease. The goal was to improve the quality of life of the participants by assisting them to cope and manage more effectively. The project employed the health promotion mechanisms of self-care and mutual aid. Follow-up revealed that the group participants found that they were able to cope more effectively in living with their chronic condition. This project may provide an effective model for health promotion interventions for persons with chronic conditions and disabilities. PMID- 2207960 TI - A telephone survey to measure risk factor prevalence in communities across Canada. AB - From 1985 to 1988, 10 Canadian community health units, in conjunction with Health and Welfare Canada, conducted a standardized telephone survey to assess the prevalence of health risk factors among persons aged 15 and over. Seatbelt use, hypertension awareness, physical activity, smoking, alcohol use, cancer screening status and sociodemographic variables were ascertained in each community. Although prevalence rates for most of the major risk factors varied significantly among the survey communities, little clustering of high or low risk levels was observed in any particular locale. Periodic administration of the risk factor survey in communities across Canada would provide a valuable data base for both public health planners and researchers. PMID- 2207961 TI - A comparison of Ontario health and sanitation requirements for day nurseries with that of other provincial and state legislation. AB - Comprehensive minimum licencing standards for child day nurseries were obtained from four Canadian provinces and five U.S. states for the purpose of comparison with current Ontario health and sanitation requirements pertaining to day nurseries. Over 30 provisions dealing with sanitation, infection prevention, and child health and safety were examined. Our review has highlighted deficiencies in Canadian provincial legislation compared with state minimum licencing standards; we provide recommendations for the updating of Ontario provincial day nursery legislation to correct perceived regulatory weaknesses. PMID- 2207963 TI - [Descriptive study of cercarian dermatitis in Quebec]. PMID- 2207962 TI - Suicide in Canada: an epidemiological assessment. AB - Suicide rates in Canada rapidly increased during the 1960s and 1970s. More recent analysis of these trends indicates that in males suicide rates have stabilized and in females a notable decrease has been identified. The greatest changes in suicide rates have occurred among the youngest age groups (15 to 19), while little change has occurred in suicide mortality rates for males aged 50 years and over. The age-specific death rates in 1986 are uniformly distributed in males above age 20, while in females an inverted "U" curve is demonstrated with the peak at age 45-50. Males continue to have higher rates and the difference between males and females is expanding. A birth cohort analysis indicates that the contribution of the birth cohort to explaining suicide rates has diminished and been replaced by a more recent period effect. Suicide remains the second most important cause of death of persons between 15 and 34 years of age. Provincial variation is discussed through geographic variation, cause-specific rankings and potential years of life lost. In contrast to national trends, suicide mortality in Alberta, Quebec and New Brunswick continues to increase. An atlas is provided to display Canadian census divisions that exhibit elevated rates of suicide. PMID- 2207964 TI - The institutionalization of food banks in Canada: a public health concern. PMID- 2207965 TI - Nursing's role in the health care crisis. PMID- 2207966 TI - Certification for specialty practice. PMID- 2207967 TI - A scarce professional: the geropsychiatric clinical nurse specialist. AB - The purpose of this paper is threefold: (1) to provide detailed data to substantiate the urgent need for geropsychiatric clinical-nursing specialists (GCNSs), (2) to suggest curricula content areas for GCNSs, and (3) to discuss potential topics for research on mental health and the aged. The GCNS is a rare professional; therefore, rationale is provided for the need for increasing the quantity and the quality of GCNSs. The demographic changes are emphasized in this paper, and a wide array of research topics for nurse researchers are suggested. One area needing further research is reminiscence therapy. PMID- 2207968 TI - Testing for interactions: the analysis of variance model. PMID- 2207969 TI - A model for group research by master's degree RNs in advanced roles. AB - Master's prepared RNs in advanced roles are ideally prepared to do clinical nursing research. Yet lack of time, resources, and a paucity of confidence have limited such scholarly pursuits among nurses in specialty roles. The article describes a group process by which five Master's prepared nurses (three clinical specialists, two Nursing Educators) successfully investigated and implemented a Nurse Research Interest Group (NRIG). The facilitators and obstacles are described as well as the past, present, and future activities of this group. PMID- 2207971 TI - The clinical nurse specialist--luxury or necessity? PMID- 2207972 TI - Role development of the clinical nurse specialist within the Indian Health Service. AB - The clinical nurse specialist is employed in many health care facilities to improve patient care. One service unit of the Indian Health Service has expressed interest in the development of this role. At the present time, there are no advanced practitioners within this facility. Development, as well as implementation of the role, must be based on the cultural and health care needs of the Indian people. This paper discusses development of the role of perioperative clinical nurse specialist, based on personal experience, at a service unit providing health care to a large tribe of American Indians in the Southwestern United States. Examples of care incorporating cultural practices, are used to illustrate the practice of the perioperative specialist within the Indian Health Service. The nursing process is used to organize the development of the role. PMID- 2207970 TI - Implementing the research role of the clinical nurse specialist--one institution's approach. AB - The mandate of the clinical nurse specialist (CNS) is to perform research. This paper reviews the historical basis for this mandate and outlines the obstacles encountered by CNSs in fulfilling it. The CNS is often torn between two time consuming responsibilities: patient care and research. Without a systematic approach, supported by the institution, that provides both material resources and time to conduct clinical studies, research is deemphasized. By establishing a seminar that assisted CNSs in developing research proposals, one institution effectively overcame these obstacles. PMID- 2207973 TI - The clinical nurse specialist role in the Army Medical Department. AB - Although clinical nurse specialists (CNSs) have been in the Army Medical Department for more than 10 years, there are no reports in the literature regarding role implementation for them. In this study, a survey of all practicing CNSs in the Army Medical Department (AMEDD) and their supervisors was conducted with the purpose of defining their perceived role and the value placed on it by their supervisors. The results showed that the study population (n = 52) has implemented the role with all components (practice, education, consultation, administration, and research) considered important by them. Further, 85% of the CNSs report positive job satisfaction, and 67% believe they have reached role maturation. Their supervisors were equally or more positive about the importance of the role, and all (n = 26) felt it must be maintained despite budget constraints and nursing shortages. Findings were that CNSs experience role satisfaction, have achieved role maturation, and are valued by their supervisors within the AMEDD. PMID- 2207974 TI - Strategies for implementing advanced practice. PMID- 2207975 TI - Paradigm case analysis and stimulated recall: strategies for developing clinical reasoning skills. AB - Development of clinical reasoning skills was a major objective of a collaborative venture between a university school of nursing and a tertiary care teaching hospital. Two elective courses and an 8-month practicum were offered at the graduate level to students specializing in perinatal nursing. Through analysis of their own cases and those of clinical experts, students gained expertise in tracing the development of their decision-making skills. In the clinical practicum, where it was less feasible for the student and preceptor to withdraw from the clinical setting to discuss the decision-making process, "stimulated recall" was employed. This strategy uses segments of nurses' actual practice, on site, at the time of care delivery. In this way, the total context of the clinical reasoning process of nurses can be examined. In this paper, the two strategies are discussed with illustrations from the actual teaching/learning situations. PMID- 2207977 TI - Consultation. PMID- 2207976 TI - Achievement of group cohesion through the development of a psychiatric nursing seminar. AB - The purpose of this paper is to describe the process by which group cohesion emerged around the task of developing a psychiatric nursing seminar at the Palo Alto (California) V.A. Medical Center. This paper will discuss how group cohesion evolved, describe the seminar, and offer suggestions to other nurses wanting to work together more collaboratively. As clinical nurse specialists (CNS) assigned to the inpatient psychiatric units of a Veterans Administration Medical Center, we were asked by nursing administration to develop an educational course. The purpose of the course was to provide registered nurses with a common knowledge base that would facilitate communication related to patient care. While we were aware that teaching discreet areas of content commensurate with our individual interests and expertise would get the job done rapidly, our combined experience taught us that this approach to learning did little to bring about a change in clinical practice. We viewed the selection of a conceptual framework to which we could all be committed as an essential step prior to the content development. What is significant about this experience was that the group process of achieving cohesiveness was so closely related to the conceptual framework that finally evolved. We chose a framework that reflected our own perspectives towards working with others and about psychiatric nursing. In turn, the major concepts of the chosen framework guided many of our interactions with each other. PMID- 2207979 TI - Child psychiatry: an overview. PMID- 2207978 TI - Use of diffusion of innovation model for agency consultation. AB - Change is an ongoing phenomena in organizational life. The consultant role is often that of assisting organizations in the formulation and management of institutional change. The use of the Diffusion of Innovation Model by the nurse consultant as a tool for change management can make the difference between well accepted change and programs that are doomed to failure. This article presents Rogers' Diffusion of Innovation model, identifies the stages in the innovation process for organizations, demonstrates how the model can be applied to organizational change and proposes its use by nursing consultants. PMID- 2207980 TI - Children's observations of violence: I. Critical issues in child development and intervention planning. AB - Children are often the unintended or indirect victims of wife abuse as witnesses of this violence in their family. Current research on these children and a conceptual framework to understand how this violence affects their development are outlined. The implications of this research are discussed in terms of several intervention strategies. The importance of primary prevention programs in school systems is stressed. PMID- 2207981 TI - Children's observations of violence: II. Clinical implications for children's mental health professionals. AB - This paper discusses the clinical implications of our current knowledge about children exposed to violence. It highlights a number of typical case scenarios in which mental health professionals have responded inadequately to the issue of violence. Alternative strategies for assessing and treating children exposed to violence are offered which have both therapeutic and preventative value. Finally, a family based assessment and treatment approach, which may be appropriate in a number of cases, is suggested. PMID- 2207983 TI - Psychosocial and erotic development in cross-gender identified children. AB - This article reviews certain aspects of psychosocial and erotic development in cross-gender identified children. Consideration is first given to the hypothesis that cross-sex affiliation preference and its attendant social ostracism is one factor that accounts for the presence of behavioural psychopathology in cross gender identified boys. Next, the strong relation between patterns of childhood sex-typing and later sexual orientation is discussed. It is concluded that more attention should be given to the study of erotic development in its own right. PMID- 2207982 TI - Gender identity disorder and psychosexual problems in children and adolescents. PMID- 2207984 TI - The relevance of a systemic model for the study and treatment of anorexia nervosa in adolescents. AB - A systems model describing interactions between social, familial, intrapsychic and physiological levels in anorexia nervosa is described. The role of escalating positive cycles in producing severe pathology is emphasized. The general relevance of the model for understanding different clinical pictures and for focusing treatment interventions and further research is outlined. PMID- 2207985 TI - Preschool age children of divorce: transitional phenomena and the mourning process. AB - The role of the family home as an attachment object was investigated in 57 preschool age children coping with the stress of a parental divorce. Results indicated that preschool age children of divorce exhibited an increased level of attachment to the family home as compared with children matched for age and socioeconomic status from intact family units who moved away from the family home. In addition, preschool age children who moved from the family home but show a high attachment to it demonstrate better behaviour adjustment than both the groups of children of divorce who showed low attachment after moving from the family home and the group who remained living in the family home after divorce (p less than .05). PMID- 2207986 TI - Evaluation of the effectiveness of a psychodynamically oriented day treatment program for children with behaviour problems: a pilot study. AB - Twenty-three consecutive admissions to a psychodynamically oriented day treatment program were assessed using a pre-/post-test design. Discharge scores revealed a significant improvement on all standardized scales for behaviour (p less than .0001), academics (p less than .05), personality measures (p less than .0001) and family measures (p less than .05). Parents reported a significantly greater behavioural improvement than both teachers and primary therapists (p less than .0001). Although all children showed improvement, parents reported significantly lower improvement rates (p less than 0.05) for children with conduct disorder compared with attention deficit disorder, oppositional defiant disorder and depression. Teachers found that younger boys (aged six to nine) showed a significantly greater improvement (p less than .05) than older boys (aged ten to 12) in total behaviour score and externalizing subscores of the Revised Child Behavior Profile. At discharge 87% of children were reintegrated into regular school; only 17% were attending regular school at admission. PMID- 2207988 TI - Feeding disorders in infancy: classification and treatment considerations. AB - This paper critically discusses conceptualizations of failure to thrive as an organic and nonorganic dichotomy. Research findings are used to refute this type of categorization. Instead, an approach which recognizes both organic and nonorganic influences and consequences of the syndrome are suggested. Physical, psychological and interpersonal systems and their interactions are explored. Potential contributions of the psychiatrist in the context of a multidisciplinary team approach to treatment are described. PMID- 2207987 TI - A pilot study of panic attacks in a child and adolescent psychiatric population. AB - This preliminary study examines the prevalence of panic attacks in a child and adolescent psychiatric population through a questionnaire survey of child psychiatrists. Panic attacks were reported in 26% of the sample. The rates varied with patient diagnosis, age, and sex. PMID- 2207989 TI - Native ethics and rules of behaviour. AB - Psychiatrists assessing Native children and adolescents often find them passive, difficult to assess and not forthcoming. This behaviour, which actually reflects the influence of Native culture, is often misinterpreted by clinicians unfamiliar with that culture as evidence of psychopathology. Patterns of conflict suppression, conflict projection and the humiliating superego are described and placed in their historical and cultural perspective, where they originated as techniques of ensuring the group unity and cohesion essential for survival in a hostile environment. Failure to recognize and understand such cultural influences can lead to errors in diagnosis and treatment that can turn what was intended as a helpful encounter into a destructive one. PMID- 2207990 TI - Anorexia resulting from fear of vomiting in four adolescent girls. AB - Four adolescent girls were referred for psychiatric assessment because of suspected anorexia nervosa. Although all of them had lost at least 15% of their body weight, investigation showed that they did not meet the criteria for anorexia nervosa. In all cases, refusal to eat resulted from fear of vomiting following a viral illness and not from a desire to lose weight. Their family configurations and personal histories showed many similarities, including constricted range of affect and a notable lack of anger. With counseling and, in one case, psychotropic medication, the patients recovered promptly. PMID- 2207991 TI - A mandatory clinical clerkship in child psychiatry: a description and evaluation. AB - We describe a mandatory clinical clerkship in which students spend one day a week for six weeks assessing and treating a child and family and participate in seminars on common child psychiatric syndromes and their treatments. In two of three settings, two students were assigned to each child and family and in the third setting, one student was assigned. We assessed their satisfaction by a mailed survey and found each student seemed to be satisfied with his/her own experience. The administrative advantages of having two students for each family are outlined. Also a rank order of preference of seminar content was assessed. Seminars on depression, conduct disorders, attention deficit disorders and family assessment were most appreciated. PMID- 2207992 TI - Adolescent day program: a two year retrospective review. AB - The place of a psychiatric day treatment program within the spectrum of necessary treatment options is noted in the literature review. A established day program is described with some characteristics of 97 youths attending the program over a two year period. The authors highlight those characteristics which correlate with benefits derived from program attendance. PMID- 2207993 TI - The New York Longitudinal Study (NYLS): the young adult periods. AB - This paper focuses on the findings and analyses, both qualitative and quantitative, of the young adult periods; early adult life (EAL) or ages 18 to 24, and young adult life (YAL) or ages 25 to 30. A summary is given of the sample and methods used in the study. Complexities of the life paths of the 133 subjects are traced, and the adolescent findings are discussed. In this middle class sample, the YAL period was found qualitatively to demand greater resolution of goals, life patterns and self-sufficiency than earlier periods. PMID- 2207994 TI - In Freud's defence. PMID- 2207995 TI - The effect of the gastrin receptor antagonist proglumide on survival in gastric carcinoma. AB - Gastric cancer remains a disease with a very poor prognosis, and there is no safe and effective form of therapy for advanced disease. Evidence is now abundant to show that gastrin stimulates the growth of both gastric and colorectal cancer cells in vitro and in vivo, and that blockade of gastrin receptors can prolong survival in xenografted nude mice. We have thus performed a randomized, controlled study of the gastrin/cholecystokinin receptor antagonist proglumide as therapy in 110 patients with gastric carcinoma. Proglumide had no overall effect on survival (Mantel-Cox statistic = 0.5, P = 0.48). The 95% confidence interval for the proglumide treated group was 260 to 474 days compared to 230 to 372 days for the control group. No significant difference was seen with proglumide, which has a relatively low affinity with the gastrin receptor and also has partial agonist activity. Drugs that are far more specific and potent gastrin receptor antagonists are becoming available, which may have a greater effect on survival, and further clinical trials of such compounds are clearly indicated to determine the efficacy of hormonal control of gastrointestinal malignancy. PMID- 2207996 TI - Treatment of patients with isolated axillary nodal metastases from an occult primary carcinoma consistent with breast origin. AB - The records of 42 patients who had axillary metastases compatible with a clinically occult breast primary were reviewed. Forty patients had mammography performed as part of their evaluations. Mastectomy yielded the primary tumor in one of 13 patients; biopsy yielded positive results in one of five. Among the 29 patients who did not undergo mastectomy, 16 received breast irradiation, and 13 were simply observed for signs of the primary tumor. For the patients who did not undergo mastectomy, the 5-year actuarial risk for appearance of a primary was 17% in the irradiated group versus 57% in the nonirradiated group (P = 0.06). Patterns of failure are correlated with stage and local and systemic therapy. The results affirm our belief that patients with axillary metastases histologically consistent with breast tumor should be treated identically to patients with similar nodal stages and proven breast primaries. PMID- 2207997 TI - Cancer chemotherapy after solid organ transplantation. AB - To assess how well chemotherapy is tolerated after solid organ transplantation, we reviewed our experience at the Children's Hospital of Pittsburgh with five patients aged 1 to 12 years. Four patients had a liver transplant, indications for which were hepatoblastoma in two patients, hepatic failure secondary to Wilms' tumor chemoradiotherapy in one patient, and familial intrahepatic cholestasis in one patient. A fifth patient received a cardiac transplant for unresectable angiosarcoma of the right atrium. After transplant, chemotherapy was given for the treatment of the primary malignancy in four of the patients. The patient with familial intrahepatic cholestasis received chemotherapy for secondary lymphoproliferative disease that had not responded to the cessation of immunosuppression. All patients other than this patient were on immunosuppression with prednisone (0.5 to 2 mg/kg daily) and cyclosporine (to maintain serum levels at 800 to 1000 ng/ml radioimmunoassay) throughout the duration of chemotherapy. Courses of chemotherapy included one or more of the following agents: Adriamycin (Adr, 20 mg/m2 daily, three patients), Cyclophosphamide (Ctx, 1 gm/m2, one patient), cisplatin (CDDP, 90 mg/m2, one patient), Vincristine (Vcr, greater than 0.75 to 1.5 mg/m2, three patients), Actinomycin D (Act-D, 7.5 micrograms/kg, one patient), Ifosfamide (I, 1800 mg/m2, one patient) and Etoposide (VP-16, 100 mg/m2, one patient). All patients received greater than or equal to 3 courses (range, 3 to 9; mean, 5) of chemotherapy every 3 to 4 weeks. Dose reductions were made because of neutropenia in three patients but none were greater than 50%. Severe rejection was seen in one patient who had, however, manifested evidence of rejection prior to his first postoperative course of chemotherapy. No nephro or cardiac toxicity was seen. This preliminary experience suggests that chemotherapy is well tolerated after solid organ transplantation. PMID- 2207998 TI - Autopsy-documented cure of multiple myeloma 14 years after M2 chemotherapy. AB - Multiple myeloma was diagnosed in a 65-year-old woman in 1974 who thereafter received five-drug M2 chemotherapy. All protein abnormalities subsequently returned to normal and serial bone marrow studies documented complete bone marrow remission. Destructive bone lesions persisted radiographically, but did not progress. In 1987, a localized sigmoid adenocarcinoma was resected. In 1988, the patient presented with multiple brain metastases associated with a primary pulmonary adenocarcinoma that proved rapidly fatal. At autopsy, no evidence of multiple myeloma was found. This report describes the first tissue-documented cure of multiple myeloma 14 years after diagnosis and initiation of M2 chemotherapy. The possible association of multiple myeloma with other malignancies is also discussed. PMID- 2207999 TI - Pulmonary metastases from ameloblastoma of the mandible treated with cisplatin, adriamycin, and cyclophosphamide. AB - A case of delayed pulmonary metastases from an ameloblastoma of the mandible, which occurred 20 years after surgical resection of the primary tumor but with no recurrence at the primary site, is reported. Combination chemotherapy using cisplatin, adriamycin, and cyclophosphamide has produced a very good clinical and radiologically documented response in this case. PMID- 2208000 TI - Relationship of 4F2 antigen with local growth and metastatic potential of squamous cell carcinoma of the larynx. AB - The 4F2 antigen is a cell-membrane glycoprotein which arises early in the G0-G1 phases of the cell cycle. This molecule is present in all established human cell lines and most malignant human cells. The authors used an indirect immunophosphatase method to study 50 squamous cell carcinomas of the larynx and ten lymph-node metastases, corresponding to six primary tumors, for 4F2 expression. The tumors showed several patterns of 4F2 staining which were correlated with different behaviors and prognoses of the neoplasms. Three different patterns (no staining, peripheral staining, and diffuse 4F2 expression) are described as are their relationships with metastatic behavior of the carcinomas. Tumors with metastases were found only in the third group (P = 0.0001). These results led to the following conclusions: (1) the 4F2 antigen is present in squamous cell carcinomas; (2) its distribution reflects the tumor spreading pattern; and (3) it correlates with differentiation and metastatic behavior. PMID- 2208001 TI - Tumor-antigen 4. Its immunohistochemical distribution and tissue and serum concentrations in squamous cell carcinoma of the lung and esophagus. AB - The immunohistochemical distribution and concentrations of tumor-antigen 4 (TA-4) in tissues and serum were determined in patients with benign and malignant diseases, including 27 patients with squamous cell carcinoma (SCC; 15 in the lung and 12 in the esophagus). Tumor-antigen 4 immunoreactivity was present in the cytoplasm of many SCC tissues, especially in the hyperparakeratotic region, and in the cytoplasm of differentiated squamous cells of the intermediate layer of normal epithelia of various organs, but not in those of other types of lung cancers or benign pulmonary diseases. Consistent with the results of immunostaining, the TA-4 concentrations in SCC tissues of the lung, esophagus, and normal squamous epithelia were much higher than in those of lung cancer other than SCC, benign pulmonary diseases, normal lung, and submandibular gland tissues. The TA-4 concentration in SCC tissue tended to increase with increasing grades of differentiation. Serum TA-4 was elevated in 15 of 27 patients with SCC but in no patients with other types of lung cancer or benign diseases. These results indicate that TA-4 is an antigen related to the differentiation of squamous cells and that tumor cells of SCC can release a large amount of TA-4 into circulation whereas normal squamous epithelia cannot. PMID- 2208002 TI - Myocarditis or acute myocardial infarction associated with interleukin-2 therapy for cancer. AB - The hearts of eight patients aged 22 to 67 years (mean, 41 years) who died during or within 4 days of interleukin-2 (IL-2) based immunotherapy for treatment of renal cell carcinoma or melanoma were studied at necropsy. Death resulted from combined cardiorespiratory failure in two patients, sepsis in four patients, acute myocardial infarction in one patient, and myocarditis in one patient. Transmural left ventricular necrosis was present in one of the two patients with significant atherosclerotic coronary artery narrowing. Noninfectious myocarditis was present in five patients: the inflammatory infiltrate was lymphocytic in four and composed of a mixture of eosinophils and lymphocytes in one. Although treatment-related deaths associated with high-dose IL-2 therapy are uncommon (1.5% in 652 consecutive patients), the potential for significant myocardial ischemia or myocarditis exists, and careful monitoring for arrhythmias or myocardial failure is warranted. PMID- 2208003 TI - Postoperative active specific immunization in colorectal cancer patients with virus-modified autologous tumor-cell vaccine. First clinical results with tumor cell vaccines modified with live but avirulent Newcastle disease virus. AB - Sixteen patients with colorectal carcinoma Dukes' Stage B2, C, or D were treated with an autologous virus-modified tumor-cell vaccine after potential curative tumor resection (R0-Resection). An inoculum of 1 X 10(7) cells incubated with 32 hemagglutination units of nonirradiated Newcastle disease virus (NDV) was given intracutaneously up to four times at 10-day intervals. The delayed-type hypersensitivity (DTH) skin reaction was measured. The vaccination was well tolerated. In 11 of 16 patients an increasing reactivity against the vaccine was observed during the vaccination procedure. A challenge test using autologous tumor cells without NDV after the vaccination cycle revealed a specific antitumor sensibilization in 12 patients. The DTH response was not due to bacterial contamination or sensibility to the virus. Histologic examination of the vaccination site showed a dense infiltration of predominantly helper T lymphocytes. We conclude that in most of the patients treated active, specific immunization led to a specific antitumor sensitivity. PMID- 2208004 TI - Acute T-cell leukemia/lymphoma mimicking Hodgkin's disease with secondary HTLV I seroconversion. AB - The authors observed a pleiomorphic lymphoma mimicking Hodgkin's lymphoma in a French Guyana black woman lacking antibodies for human T-cell lymphoma/leukemia virus type I (HTLV I). After two courses of chemotherapy with either mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or doxorubicin, bleomycin, vincaleukoblastine, and dacarbazine (ABVD), a typical acute T-cell leukemia/lymphoma developed with HTLV I seroconversion. Specific HTLV I DNA sequences were detected using the polymerase chain reaction (PCR) on a lymph node biopsy obtained before chemotherapy. The mechanisms of the seroconversion are discussed. PMID- 2208005 TI - Immunohistochemical studies on the main entrance-route of CA19-9 into the peripheral venous blood of gastric cancer patients. Correlation with CA19-9 levels in peripheral and portal blood. AB - The correlation between CA19-9 levels of portal and peripheral venous blood, and immunohistochemical variables of cancer lesions was examined in 53 gastric cancer patients and eight patients with benign diseases. Immunohistochemically, CA19-9 was found in 33 (62.5%) of 53 primary lesions. The antigen was found in the cancer cells of invasive lymphatics and node metastases of every CA19-9 localized cancer, although the cancer cells in veins showed little or no CA19-9. There was little or no antigen in the cancer cells in veins, lymphatics, or metastases of 20 CA19-9 nonlocalized primary lesions. Patients with CA19-9 nonlocalized cancer or with benign diseases showed no elevation of the antigen levels in peripheral or portal blood. CA19-9 levels of portal blood (mean, 76.4 U/ml; positive rate, 33.3%) were not different from those of peripheral blood (mean, 91.5 U/ml; positive rate, 33.3%). Additionally, the antigen levels of the blood in patients with lymphatic invasion or node metastases were significantly higher than those in patients without the invasion or the metastases, and every patient without the invasion showed no elevation of the antigen. These results suggest that production of the antigen in cancer cells may be a premise of CA19-9 elevation in peripheral blood and that CA19-9 may be drained by the thoracic duct of the lymphatic system via node metastases or invasive lymphatics, but not by the hematogenous portal system. PMID- 2208007 TI - Regional differences in the intranodal distribution of tumor cells. AB - The intranodal distribution of tumor cells was examined in 103 mesenteric and 135 axillary nodes to determine the frequency of a circumferential type of distribution and its relationship, if any, to central necrosis. Eighteen percent of the mesenteric nodes removed at surgery from patients with colon cancer contained a circumferential rim of viable tumor cells in an area corresponding wholly or in part to the normal location of the marginal sinus. In each case this rim of tumor cells surrounded a large central area of necrosis. In contrast, only one of the 135 axillary nodes removed from patients with breast cancer demonstrated this pattern. These findings suggest that by interrupting blood and lymph vessels, the circumferential spread of tumor cells underlies development of central necrosis. Previously described structural dissimilarities between mesenteric and axillary nodes may explain the striking difference in incidence of this pattern in these nodes. PMID- 2208006 TI - Colonic polyamine content and ornithine decarboxylase activity as markers for adenomas. AB - Polyamine content (putrescine, spermidine, and spermine) or ornithine decarboxylase (ODC) activity was measured in normal-appearing colonic mucosa from patients undergoing colonoscopy. Comparisons were made between those with and those without adenomatous polyps. Colonic mucosal polyamine content was measured in 44 persons. Mean putrescine content was 1.25 +/- 0.26 (SE) nmol/mg protein in 22 patients with adenomatous polyps compared with 0.53 +/- 0.12 nmol/mg protein in patients without polyps (P less than 0.02). Tissue content of spermidine and spermine did not differ between these two groups. Ornithine decarboxylase activity was measured in tissue from 45 patients. Mean ODC activity was 2.84 +/- 0.73 pmol/hr/mg protein in 23 persons with adenomatous polyps compared with 1.15 +/- 0.18 pmol/hr/mg protein in persons without polyps (P less than 0.05). Mucosal putrescine and ODC activity are elevated in patients with adenomatous polyps compared with patients without polyps. These biochemical markers may prove helpful in improving surveillance methods for colorectal cancer and premalignant adenomatous polyps. PMID- 2208008 TI - Flow cytometric DNA analysis of parathyroid tumors. Implication of aneuploidy for pathologic and biologic classification. AB - The previous cytometric studies on parathyroid tumors have provided conflicting data regarding the relationship between DNA content and histopathology, resulting from differences in technical methods and data analysis. This study measured nuclear DNA of parathyroid tumors by flow cytometry in fresh material and determined whether DNA aneuploidy really assists in making a pathologic diagnosis of carcinoma or not. From May 1987 through April 1989, 65 consecutive patients operated on for primary hyperparathyroidism had DNA analysis of the freshly excised parathyroid tumors. Three of the patients had metastatic lesions of parathyroid carcinoma in the lung, cervical lymph nodes, and lung and mediastinal lymph nodes, respectively. Pathologic classifications of the lesions from the other 62 patients were 54 adenomas, four carcinomas, and four hyperplasias. In all the latter patients, hyperplasia was associated with a multiple endocrine neoplasia syndrome. Unequivocal evidence of aneuploidy was found in all of the metastatic lesions and 60% of the primary lesions of the carcinomas, in 9% of the adenomas and in 50% of the hyperplasias. Therefore, parathyroid carcinomas were more apt to be aneuploid than were adenomas (P = 0.0015, both-sided testing). In each of the cases of aneuploid hyperplasia, a small aneuploid peak was found. The high incidence of aneuploidy in patients with multiple endocrine neoplasia type 1 may indicate the presence of clonal heterogeneity of hyperplastic glands and the presence of an abnormal subset of cells that have malignant potential. Cell distribution analysis did not provide any significant information beyond ploidy level. In conclusion, DNA flow cytometric analysis of DNA ploidy patterns is a valuable adjunct to the histopathologic diagnosis of parathyroid neoplasms. PMID- 2208009 TI - Brush cytology in the diagnosis of colonic neoplasms. AB - During a three-year period (1986-1988), 234 colonic brush specimens were received in the authors' laboratory. Nine samples (4%) were deemed unsatisfactory for evaluation because of inadequate cellularity and/or poor fixation. In 11 cases concomitant or follow-up histologic specimens were not available. The remaining 214 specimens included 82 malignant neoplasms, 88 neoplastic polyps (adenomas), and 44 nonneoplastic lesions. Sixty-seven (82%) of malignant neoplasms were correctly diagnosed by brush cytology. Three cases of adenoma with severe dysplasia or in situ carcinoma were diagnosed as adenocarcinoma by cytology. No false-positive diagnoses were made of nonneoplastic lesions. Brush cytology was found to be a more sensitive technique in the diagnosis of colon cancer than endoscopic biopsy (82% and 74% sensitivity, respectively). The combination of the two techniques increased the sensitivity to 90% and improved the overall accuracy of the test. Seventy-one (82%) of the colonic adenomas were correctly diagnosed by cytology. Brush cytology is a convenient, safe, and accurate technique which should be used concurrently with endoscopic biopsy or polypectomy. PMID- 2208010 TI - Soft tissue sarcoma with additional anaplastic components. A clinicopathologic and immunohistochemical study of 27 cases. AB - This clinicopathologic study concerns 27 cases of "dedifferentiated" soft tissue sarcoma (DSTS), including 14 liposarcomas, six leiomyosarcomas, five chondrosarcomas, and two rhabdomyosarcomas. In addition, the authors conducted an immunohistochemical survey of 23 cases and an electron microscopic examination of three. The findings were compared with observations of 32 cases of de novo malignant fibrous histiocytoma (MFH). All tumors contained additional distinct anaplastic portions indistinguishable from MFH under conventional light microscopy, ultrastructurally, and in cases of immunoreactivity for alpha-1 antichymotrypsin and alpha-1-antitrypsin and on lectin histochemical findings for ricinus communis agglutinin and concanavalin agglutinin. The desmin reactivity present in anaplastic portions of 14 DSTS and in eight de novo MFH is taken to mean that myofibroblasts are present in these tumors. The anaplastic components of DSTS are presumed to represent the proliferation of another clone of undifferentiated mesenchymal cells that fail to differentiate along any specific lineage other than fibroblast-like cells, histiocyte-like cells, and myofibroblasts. Nineteen patients died of tumor and four are alive and well 1.6, 1.7, 2.1, and 5.2 years after the initial treatment, respectively. PMID- 2208011 TI - Clinical prognostic factors in patients with posterior uveal malignant melanoma. AB - The authors evaluated the prognostic value of clinically assessed variables for predicting length of survival until death from metastatic disease in 237 patient with a primary choroidal or ciliary body melanoma. Using multivariate Cox proportional hazards modeling, the authors identified the largest linear basal tumor diameter (mm), estimated by indirect ophthalmoscopy and fundus drawing, the location of the anterior margin of the tumor relative to the ocular equator and ora serrata, and the age of the patient at the time of treatment as the best combination of the clinically assessed variables for predicting survival. For each patient in this group, the authors computed a prognostic index based on the best multivariate Cox model. They showed that patients with low, intermediate, and high values of prognostic index had low, intermediate, and high melanoma related mortality rates, respectively, during the first 5 to 8 posttreatment years. These results suggest that: (1) clinically assessed variables evaluated according to a standardized protocol are useful for predicting the survival of treated patients with posterior uveal melanoma and (2) ophthalmologists who assess potential clinical prognostic variables consistently may identify subgroups of patients with comparable mortality risk on the basis of noninvasive testing. PMID- 2208012 TI - Mammographic screening of women with increased risk of breast cancer. AB - Five hundred one women from Dallas County, Texas who participated in the American Cancer Society 1987 Texas Breast Screening Project were selected because of a self-reported family history of breast cancer (cases). They were matched with 501 randomly selected women from the same county with no family history (controls). Although there was a statistically significant trend with age for an increasing proportion of women to report having undergone mammography, there was no significant difference when comparing mammographic histories of cases with controls after controlling for age (31.5% versus 35.1%, P = 0.33). Significantly more cases (79%) perceived their risk for breast cancer to be moderate or greater compared with controls (54%, P less than 0.0001), but mammographic histories were not different when controlling for perceived risk. Both cases and controls cited lack of physician referral and cost as their reasons for not having undergone mammography. Women at increased risk for breast cancer (because of their family history) are not undergoing regular mammographic screening despite their self awareness of the increase in their risk. PMID- 2208014 TI - Analysis of bladder carcinoma by subsite. Cystoscopic location may have prognostic value. AB - Nine hundred fourteen cases of carcinoma of the urinary bladder registered from 1977 to 1988 with the Kansas state tumor registry were evaluated by subsite for differences in grade, histology, sex, age at diagnosis, and survival. Only initial occurrences of carcinoma were included. Carcinoma of the lateral walls accounted for 37.1%; the posterior wall, 17.9%; the trigone, 12.6%; the neck, 11.1%; the ureteric orifices, 9.8%; the dome, 7.7%; and the anterior wall, 3.8%. Malignant neoplasms occurring in the neck of the bladder had a significantly poorer prognosis by survival analysis (P less than 0.05). Malignancies of the dome were found to present as higher grade lesions (P = 0.00003), and carcinoma of the ureteric orifices and lateral walls tended to be of lower grade (P = 0.02 and P = 0.05, respectively). Carcinomas of the anterior wall and dome occurred in a more elderly population (mean ages, 75.6 and 73.9 years, respectively), and carcinomas of the trigone and ureteric orifices occurred in a younger group (mean ages, 68.3 and 67.5 years, respectively). On histologic evaluation the trigone gave rise to more squamous cell carcinoma than expected (P = 0.001, 325% of expected). No distribution difference was noted among subsites with respect to sex. These data show significant differences among subsites of the urinary bladder with regard to survival, grade, histology, and age at diagnosis. PMID- 2208013 TI - Survival of premenopausal women with metastatic breast cancer. Long-term follow up of Eastern Cooperative Group and Cancer and Leukemia Group B studies. AB - In premenopausal women with metastatic breast cancer, differences in survival curves early during follow-up can be misleading. The authors therefore analyzed long-term survival in 378 patients, entered in three randomized trials, started between 1973 and 1978. Combined data from the three trials were used to increase the power for identifying prognostic variables. Cancer and Leukemia Group B (CALGB) trial 7382 randomized patients to oophorectomy plus either cyclophosphamide or combination chemotherapy or observation. Eastern Cooperative Oncology Group (ECOG) 2174 randomized patients who had not progressed 3 months after oophorectomy to combination chemotherapy or combination chemotherapy or observation. Trial ECOG 2177 randomized estrogen receptor (ER) positive or ER unknown patients to oophorectomy plus combination chemotherapy or immediate combination chemotherapy, and ER-negative patients were directly assigned to combination chemotherapy. Hence ER-negative patients need not have been healthy enough to be randomized to oophorectomy. With only 14% of the patients still alive, median survival on the three studies was 30, 24, and 28 months. The median survival of individual treatments changed noticeably in ECOG 2174 and ECOG 2177 with long-term follow-up. At this time there are no differences in survival between randomized regimens in any of the three trials. In a multivariate model, factors associated with significantly poorer survival were visceral-dominant disease, nodal metastases, breast metastases, age younger than 45 years, ER negativity, and not receiving chemotherapy immediately after oophorectomy. This treatment difference was thus not due to imbalances in the prognostic variables used in the model, but it may be due to imbalances of unknown prognostic factors or differences in patient selection. PMID- 2208015 TI - The management of pseudomyxoma peritonei. AB - The management of nine patients with pseudomyxoma peritonei was reviewed. Aggressive surgical resection of tumor is the standard of treatment, with many patients requiring multiple laparotomies. Chemotherapy, including the use of cisplatin is not effective. Long-term nutritional support provides a better quality of survival for select patients. PMID- 2208016 TI - Chondrosarcoma of bone in children. AB - Chondrosarcoma of bone rarely occurs in children. This report analyzes the clinicopathologic features in a series of 47 patients with conventional chondrosarcoma who were less than 17 years of age. Of the 47 cases, 14 were from the Mayo Clinic files, and 33 were from our consultation files. Most of the lesions occurred in the trunk and upper ends of the long bones, with the humerus being the most frequent skeletal site. Twelve of the 47 tumors were secondary. The radiographic findings were the same as those seen in adult chondrosarcoma. Pathologically, the tumors were low grade. En bloc resection is the treatment of choice because of the high incidence of local recurrence with lesser surgical margins. Prognosis in childhood chondrosarcoma is no different from that in adult chondrosarcoma. None of the patients with follow-up data had metastasis. PMID- 2208017 TI - The scapegoat effect on food aversions after chemotherapy. AB - The effects of consuming a novel food (halva) versus a familiar food (cookies) before gastrointestinal (GI) toxic chemotherapy on patients' preference for familiar foods consumed after chemotherapy treatment were compared. The development of aversions to the novel and familiar foods was also assessed. Patients with a history of posttreatment nausea consumed either a novel or a familiar food before chemotherapy and were asked to keep a food record through the next breakfast and to rate their preference for these foods. Patients who consumed halva before treatment were significantly more likely to increase their ratings for foods consumed after chemotherapy than patients who consumed familiar cookies. Aversions to the novel food were significantly more frequent than aversions to the familiar food. These findings provide evidence that a novel but not a familiar food consumed before chemotherapy can act as a scapegoat to prevent items in the regular diet consumed after chemotherapy from decreasing in preference. Providing patients with a novel food before chemotherapy is a useful clinical intervention to reduce the likelihood of forming aversions to familiar foods consumed after chemotherapy. PMID- 2208018 TI - Cancer mortality in a higher-income black population in New York State. Comparison with rates in the United States as a whole. AB - In the 1980 Census the median family income among blacks in Suffolk County, New York (i.e., $19,604) was much higher than that for American blacks as a whole (i.e., $12,618) and 94.1% of that for American whites (i.e., $20,840), but the proportion below the poverty level was still higher for Suffolk County blacks than for American whites. Observed numbers of deaths from 1979 to 1985 for total cancers and most cancer sites in Suffolk County black men and women were not lower than expected on the basis of age-specific and gender-specific death rates for blacks in the US. Although numbers of deaths from cervical cancer and prostate cancer were slightly lower than expected in Suffolk County blacks versus American blacks, these numbers were still significantly greater than expected on the basis of death rates among American whites. Age-specific death rates for age groups 25 to 44 years to 55 to 64 years tended to be lower in Suffolk County for lung cancers in black men but not for breast cancer in black women. Specific cancer sites, which differ in the direction of the association between incidence and socioeconomic status, age, and gender must be considered in comparisons of cancer mortality by race and socioeconomic level. Implications of the comparisons were discussed with regard to the goal of reducing racial differences in cancer death rates. PMID- 2208019 TI - Tamoxifen as a risk factor for endometrial cancer. PMID- 2208020 TI - Immunocytochemical estrogen and progestin receptor assays in breast cancer with monoclonal antibodies. Histopathologic, demographic, and biochemical correlations and relationship to endocrine response and survival. AB - Breast cancer specimens from 600 women were assayed for estrogen receptors (ER) using an immunocytochemical assay (ICA) employing the monoclonal antiestrophilin antibody H222 Sp gamma. Results showed significant correlation with biochemical ER determinations as well as with tumor grade and menopausal status. In 449 cases, results of progesterone receptor assay by ICA using the monoclonal anti PgR antibody KD 68, also correlated significantly with biochemical PgR measurements. The ERICA/PgRICA positivity was significantly more frequent in postmenopausal white women. Colloid carcinomas were most likely to be ERICA positive and PgRICA positive whereas medullary carcinomas were most often negative. In 47 patients with advanced mammary carcinoma, results of ERICA and PgRICA were more closely related to endocrine response than those of ER and PgR by dextran-coated charcoal assay (DCC). In 339 women with Stage I or Stage II breast cancer, ERICA was significantly associated with disease-free survival. Analysis by Cox's proportional hazard model, however, showed PgRICA to be the best predictor of survival and disease-free survival in 197 women at the same stages of disease. These data indicate that ICA is more predictive of prognosis than biochemical ER and PgR. The ease of ICA performance coupled with these results indicate that the method is an acceptable substitute for DCC in analyzing breast cancers for ER/PgR. PMID- 2208021 TI - Teniposide (VM-26) and continuous infusion cytosine arabinoside for initial induction failure in childhood acute lymphoblastic leukemia. A Pediatric Oncology Group pilot study. AB - Twenty-six evaluable children with newly diagnosed acute lymphoblastic leukemia (ALL) who failed to achieve initial remission after receiving two to seven drugs for at least a 4-week period were given teniposide (VM-26) and continuous infusion cytosine arabinoside (Ara-C). Twenty-two received 150 mg/m2 of VM-26 on days 1 and 2 with 100 mg/2 of Ara-C as a continuous infusion on days 1 through 5; a second shortened course was given on day 14 to eight patients who had evidence of some antileukemic effect or were clinically judged able to tolerate a second course. The last four patients received three daily doses of VM-26 and a 7-day infusion of Ara-C at the same daily dosages. Twelve (48%) achieved complete remission (CR) of ALL. There was a trend toward decreasing response rates with an increasing number of drugs used in the initial induction regimen, i.e., five CR among seven patients with a prior two-drug induction attempt, six CR among 14 patients with a prior three- to four-drug induction attempt, and one CR among four patients with a prior five- to seven-drug induction attempt (P = 0.14). Ten of 17 non-T-cell patients and two of nine T-cell patients achieved remission (P = 0.10). The median time required to achieve a complete remission from the initiation of treatment was 26 days (range, 14-72 days). This period was shorter in those who required one course compared with those who required two induction courses, i.e., 25 days median vs. 44 days median. Toxicity was significant and due mainly to marrow aplasia and infection; one patient had severe prolonged VM 26-induced hypotension. Of the 12 patients entering remission, two were removed for marrow transplant and one was removed due to parental request. In the remaining nine patients, median remission duration was only 2 months (range, 1-18 months). All nine patients relapsed in the marrow. Among the entire group of 26 patients, only one patient is alive and a long-term event-free survivor (after allogeneic marrow transplant). Due to the current use of more aggressive initial induction regimens and the extremely poor prognosis in children who fail to achieve initial remission, more intensive regimens of continuation therapy or alternative therapies, such as bone marrow transplant, should be considered. PMID- 2208022 TI - Association of disease-free survival and percent of ideal dose in adjuvant breast chemotherapy. AB - The relationship between percent of ideal dose and disease-free survival was examined in 256 Stage II and III patients who participated in a 2-year breast adjuvant chemotherapy trial consisting of cyclophosphamide, methotrexate, and 5 fluorouracil (CMF) given postoperatively. When analyzed analogously to previous work, the results confirmed a dose-response relationship: that is, there appeared to be an improved disease-free survival for patients receiving higher doses of adjuvant chemotherapy. The major criticism of such an analysis is its bias. This bias was addressed by considering only patients who were still receiving therapy at 6, 12, and 24 months; then, the dose-response relationship was no longer seen. Although causality cannot be inferred, the apparent differences in disease-free survival among the dose groups can be attributed to recurrences in the first 2 years among patients receiving lower doses of chemotherapy. PMID- 2208023 TI - A phase I trial of cisplatin in hypertonic saline and escalating doses of 5 fluorouracil by continuous intravenous infusion in patients with advanced malignancies. AB - Thirty-four patients with incurable solid tumors were treated in a Phase I trial with a fixed dose of high-dose cisplatin (CDDP) administered in hypertonic saline and escalating doses of infusional 5-fluorouracil (5-FU). Five treatment levels of 5-FU, ranging from 500 to 900 mg/m2/day for 5 days, were studied. Leukopenia, thrombocytopenia, and oral mucositis were the dose-limiting toxicities encountered. Nephrotoxicity was minimal. Ototoxicity and peripheral neuropathies were rare and mild in this patient group, but most patients received only a small number of treatment cycles. Diarrhea was not dose-limiting. Two complete responses (one non-small cell lung cancer and one sweat gland carcinoma) were observed. No other major responses were noted. With the dose of CDDP set at 35 mg/m2/day for 5 consecutive days, the maximum tolerated dose (MTD) of a concurrent 5-day 5-FU infusion was found to be 900 mg/m2/day. The recommended dosages for Phase II trials are 35 mg/m2/day CDDP and 800 mg/m2/day 5-FU for 5 consecutive days. Cancers of the lung, breast, gastrointestinal tract, and genitourinary tract would be reasonable targets for Phase II studies. PMID- 2208024 TI - Effect of intraarterial versus intravenous cisplatin in addition to systemic doxorubicin, high-dose methotrexate, and ifosfamide on histologic tumor response in osteosarcoma (study COSS-86). AB - In osteosarcoma, intraarterial (IA) administration of systemic treatment has been advocated to improve local tumor response preparing for, or even obviating, definitive surgery. Because data from the literature did not unequivocally support the local superiority of IA infusion, a comparative study was started in 1986. Preoperative chemotherapy consisted of 45 mg/m2 of doxorubicin on days 1 and 2; 12 g/m2 of high-dose methotrexate on days 15 and 22; and 3 g/m2 of ifosfamide on days 29, 30, 50, and 51 followed on days 31 and 52 by intravenous (IV) versus IA tourniquet infusion of cisplatin (DDP). A strict randomization of patients was not feasible. A balanced distribution of risk factors was strived for by stratifying and allocating the appropriate patients centrally. The infusion time was prolonged from 1 to 5 hours in the IV group, and the DDP dose was reduced from 150 to 120 mg/m2 in both arms when intolerable ototoxicity became apparent. A multivariate analysis was performed to exclude a bias on the response rates from risk factor distribution and from modifications of DDP infusion time and dosage. The overall fraction of histologic good responders (greater than 90% necrosis) was not found to be different after IA versus IV treatment (34/50 [68%] vs. 41/59 [69%]). Intraarterial instead of IV use of DDP within an aggressive systemic treatment does not seem to improve the local tumor response. PMID- 2208025 TI - Topographic classification, clinical characteristics, and diagnostic delay of cancer of the larynx/hypopharynx in Torino, Italy. AB - The case series of a population-based case-control study of laryngeal and hypopharyngeal cancers in Torino, Italy, included 281 men with clinical and anamnestic data. Two hundred fifteen, 28, and 38 cancers originated from the endolarynx, epilarynx, and hypopharynx, respectively. Regions invaded by the tumor were divided into 26 subsites. A classification based on the number of invaded subsites was proposed, which agreed well with the T classification of the TNM system. Cancers originating from the hypopharynx invaded more subsites than cancers from the endolarynx, and among the latter, supraglottic were more invasive than glottic lesions. The number of invaded subsites was strongly associated with nodal involvement. Among symptoms at onset of disease and at diagnosis, patients with endolaryngeal lesions reported dysphonia and dyspnea more frequently, and patients with lesions from other regions had a higher prevalence of dysphagia, odynophagia, otalgia, and adenopathia. Clinical and epidemiologic results of this study suggest considering the endolarynx, epilarynx, and hypopharynx as separate anatomic entities. Diagnostic delay was not associated with tumor size and showed a negative trend with involvement of cervical lymph nodes, suggesting that stage at diagnosis is due to intrinsic differences in tumor aggressiveness. PMID- 2208026 TI - Long-term follow-up of 24 patients undergoing radical resection for ampullary carcinoma, 1953 to 1988. AB - Potentially curative radical pancreaticoduodenectomy for ampullary adenocarcinoma was performed in 24 patients over a 35-year period. The overall operative mortality was 12.5%. Actuarial survival rate at 5 years was 61% +/- 13.4 standard error of the mean (SEM) and subsequently remained unchanged. In the same time period, 21 patients underwent potentially curative radical pancreaticoduodenectomy for periampullary tumors of pancreatic origin. Similar analysis showed an overall operative mortality of 23.8% and a survival rate at 5 years of 27% +/- 12.5 SEM. The results of radical pancreaticoduodenectomy for ampullary carcinoma in the most recent years (1976 to 1988) were compared with those of former years (1953 to 1975). There were no statistically significant differences in the 5-year survival rate; however, the operative mortality decreased from 25% in the former period to 6.3% in the recent period. Survival was dependent on nodal status. The 5-year survival rate was 78% +/- 11.5 SEM in the absence of nodal metastasis versus 50% +/- 25 SEM in the presence of regional nodal metastasis. These findings support the concept that radical pancreaticoduodenectomy offers a realistic probability for cure in a selected group of patients with carcinomas of the ampulla of Vater. PMID- 2208027 TI - Radiographic microcalcification and parenchymal patterns as indicators of histologic "high-risk" benign breast disease. AB - Breast tissue from a forensic autopsy series of 486 women (15 to 98 years of age) was studied radiographically and by histologic sampling. Prevalence of Wolfe P2/Dy parenchymal patterns decreased with age. Radiographic nonvascular microcalcification and histologic presence of marked ductal epithelial hyperplasia and lobular microcalcification increased with age. Both of these histologic parameters of increased risk for breast cancer correlated with the presence of radiographic microcalcification and Wolfe P2/Dy parenchymal pattern. The predictive value of the radiographic parameters for presence of "high-risk" proliferative fibrocystic change increased with age. PMID- 2208029 TI - Rearrangement of immunoglobulin, T-cell receptor, and bcl-2 genes in malignant lymphomas in Hong Kong. AB - The pattern of malignant lymphomas in the Hong Kong Chinese population is characterized by a low incidence of Hodgkin's disease and follicular lymphomas. The authors studied the immunoglobulin (Ig), T-cell receptor (TCR), and bcl-2 gene rearrangement in 62 cases of malignant lymphoma in this population by Southern blot hybridization. Two cases of Hodgkin's disease showed no rearrangement of the Ig and TCR genes. All 42 cases of B-cell lymphoma had Ig heavy chain (JH) rearrangement with or without additional rearrangement of the light chains (C kappa and C lambda). One case of diffuse B-cell lymphoma had additional T-cell receptor beta-chain (C beta) rearrangement. Sixteen of 18 cases of T-cell lymphoma had C beta rearrangement, and one case of T-lymphoblastic lymphoma had additional JH rearrangement. Two of eight (25%) cases of follicular lymphoma but only one of the 34 (2.9%) cases of diffuse B-cell lymphoma had bcl-2 rearrangement that was detected by pFL-1 probe. None of the 62 cases showed bcl-2 rearrangement using the pFL-2 probe. In conclusion, the Ig and TCR gene rearrangement pattern of the lymphomas found in Hong Kong correlates well with the T-cell and B-cell lineage, which is similar to reports in the white population. However, the incidence of bcl-2 gene rearrangement in follicular B cell lymphoma is lower than that reported in the US but comparable with that in Japan. PMID- 2208028 TI - Immunophenotypes in "classical" B-cell chronic lymphocytic leukemia. Correlation with normal cellular counterpart and clinical findings. AB - This study evaluates the expression of a series of membrane antigens, normally expressed by B-lymphocytes of the lymphocytic mantle and marginal zone, in 90 selected cases of "classical" (mouse red blood cell-receptor+, CD20+, CD5+, surface immunoglobulin +/-) B-chronic lymphocytic leukemia (B-CLL) with the aim of contributing toward identifying the normal counterpart of B-CLL and any correlations between surface antigen pattern and certain clinical characteristics. Clustered (CD23, 25, 39, 40, 27, 1c, w75) and unclustered (NuB1, 7F7, KiB3) monoclonal antibodies (MoAb) were tested. Almost all cases showed high reactivity to CD23, 27, w75, 39, 40, and NuB1: expression of CD1c was very low and that of 7F7, KiB3, and CD25 was variable. The reactivity of 7F7 and KiB3 was strictly correlated, and they correlated individually with CD25. Results show that the most frequent B-CLL phenotype (CD19+, 5+, 23+, 27+, 39+, NuB1+, KiB3 +/ , 7F7 +/-, and CD25 +/-) corresponds to one or more cellular subsets in the mantle zone. No correlation was found between MoAb expression, surface immunoglobulin (SIg) class or type, clinical stage, disease activity, or age at diagnosis. The only difference (statistically borderline) was the expression of 7F7 and KiB3 (in young versus old patients). This suggests that modulations in the expression of surface antigens do not affect the clinical behavior of the disease. PMID- 2208030 TI - Significance of blasts in low-cell-count cerebrospinal fluid specimens from children with acute lymphoblastic leukemia. AB - The purpose of this study was to determine whether the presence of more than 5% blasts in a differential count of cytocentrifuged cerebrospinal fluid (CSF) with less than 6 leukocytes/microliter was predictive of central nervous system (CNS) relapse in children with acute lymphoblastic leukemia (ALL). A double concentrate method of cytocentrifuge preparation was used to analyze 4543 consecutive CSF specimens from 349 children with ALL between January 1, 1982, and September 30, 1988. One hundred nine CSF specimens from 58 evaluable children had less than 6 leukocytes/microliter and more than 5% blasts on cytocentrifuge differential count (low-cell-count specimen with blasts [LCB]). During the study period, 25 of 332 evaluable children (7.5%) had CNS leukemic recurrence. In 22 of 25 (88%), the CNS relapse was preceded by at least one abnormal low-cell-count CSF specimen. One of 34 patients with a single LCB at diagnosis (3%) had subsequent CNS relapse compared with five of eight patients (62.5%) with a single LCB during remission (P = 0.0002). Of 16 children with two or more LCB during remission, nine (56%) had CNS relapse defined by standard criteria, whereas six additional patients in this group were declared to be in CNS relapse on the basis of their repetitive LCB. Whether diagnosing CNS recurrence earlier in its course based on a modification of the definition of CNS leukemia will change the frequency of subsequent adverse events or make possible decreased intensity of CNS retreatment remains to be determined. PMID- 2208031 TI - Prognostic implication of ecto-5'-nucleotidase activity in acute lymphoblastic leukemia. AB - Ecto-5'-nucleotidase (5'-N) activity was determined in 191 patients (71 children and 120 adults) with acute leukemia. Elevated values for 5'-N were registered in common acute lymphoblastic leukemia (ALL), but blast cells of T-cell ALL (T-ALL) and common ALL antigen-negative non-T-ALL had low enzyme activity comparable with the values of acute non-lymphocytic leukemia. Dependence of remission duration on 5'-N activity was analyzed in 74 adults with ALL, treated similarly in a prospective multicenter trial. The remission curves for ALL patients with 5'-N activity lower than 10 nmol/h x 10(6) cells were substantially and significantly better than those of patients with high activity (greater than 10 nmol/h x 10(6) cells). This difference was also evident in the immunologic subclass common ALL. Statistical evaluation showed that an interaction between immunologic subtype of the blast cells and their 5'-N activity had prognostic significance for remission duration. In addition to the independent factor, initial age, this interaction was also prognostic for survival. PMID- 2208032 TI - Sex hormone receptors in human thyroid tissues. AB - The behavior of sex hormone receptors was studied in the cytosol of thyroid tissue samples in order to clarify the effects of sex hormones on diseases of the thyroid. Androgen receptor (AR), estrogen receptor (ER), and progesterone receptor (PgR) were assayed using the dextran-coated charcoal (DCC) method and analyzed by the method of Scatchard. Androgen receptor, ER, and PgR were negative in all of the cytosol prepared from normal thyroid tissues. However, the positive rates for the receptors in the neoplastic and nonneoplastic tissues were 22% for AR, 29% for ER, and 18% for PgR. Especially, the incidence of ER was significantly higher in neoplastic lesions than normal tissues. These data suggest that sex hormones, especially estrogen, may play a role in diseases of the thyroid. PMID- 2208033 TI - Lewis system alterations in gastric carcinogenesis. AB - Alterations in the expression of type 1 blood group-related antigens (Lewis a and b) were examined immunohistochemically in 371 consecutives gastric biopsy and 80 surgical specimens from patients of gastric carcinoma. The ABH and Lewis phenotype and secretor status of the patients were correlated with histologic findings. An anomalous expression of Lewis a antigen was found in 88 of 249 gastric biopsy specimens of Lewis (a-b+) phenotype patients. The prevalence of this anomaly increased with the evolution of the premalignant process, in agreement with the commonly accepted model of gastric carcinogenesis. Thus, anomalous Lewis a antigen appeared in 66.6% of gastric dysplasia cases, in 64.6% of intestinal metaplasia, in 15.4% of atrophic gastritis, and in 7.4% of superficial gastritis. No alterations were found in subjects with normal gastric mucosa. Forty-seven of the 49 Lewis (a-b+) phenotype gastric carcinoma patients showed antigenic alterations in tumor cells (anomalous Lewis a antigen in 36 and loss of Lewis antigens in 11). In 26 of these gastric specimens an anomalous Lewis a antigen was present in areas of intestinal metaplasia and/or dysplasia away from the area of neoplastic transformation. The expression of Lewis a antigen in Lewis (a-b+) phenotype patients is a frequent phenomenon in gastric neoplastic cells and could result from the blocked synthesis of Lewis b antigen with accumulation of its precursors. These findings suggest that, during gastric carcinogenesis, antigenic alterations may precede neoplastic transformation. An anomalous Lewis a antigen could constitute a significant index of severity of the histologic lesion and contribute to identifying high-risk individuals. PMID- 2208034 TI - Comparison of DNA content in gastric cancer cells between primary lesions and lymph node metastases. AB - Cytophotomtric DNA contents of tumor cells in primary lesions and the corresponding metastatic lymph nodes were compared in 61 cases of gastric cancer to determine whether the DNA content remains stable during lymph node metastasis. The DNA distribution patterns were grouped into three types, according to the proportion of aneuploid cell population. Changes in DNA patterns between primary and metastatic lesions were evident in 36 of 61 patients (59.0%); in the remaining 25 (41.0%), the same DNA distribution patterns were noted for both lesions. In 33 of these 36, DNA pattern in the primary carcinoma was transformed into a more narrowly scattered one in the metastatic lesion of the lymph node. Mean and modal values and the frequency of cells over tetraploid (4c) or hexaploid (6c) were significantly higher in the primary lesion compared with findings in the metastatic lesions. This reduction in DNA content in the metastatic lesions was a more frequent occurrence in differentiated (18 of 23) than in undifferentiated adenocarcinoma (15 of 35) (P less than 0.01). Therefore, in primary lesions with a widely scattered DNA ploidy, the tumor cells with a smaller DNA ploidy frequently metastasized to lymph nodes, particularly in cases of a differentiated carcinoma. Such observations may be pertinent in future designing of treatment protocols. PMID- 2208035 TI - A clinical and flow cytometric analysis of patients with nasopharyngeal cancer. AB - Abnormal cellular DNA content, a hallmark of malignancy, is known to be an important prognostic factor in many human solid tumors; however, no data have been published on whether cellular DNA content carries prognostic significance for patients with nasopharyngeal cancer (NPC). Archival, formalin-fixed, paraffin embedded pathology specimens representing pretreatment tissue biopsies from 55 patients (41 men and 14 women) with NPC were analyzed for cellular DNA content in a retrospective fashion from 1968 to 1988. Individual tumors were classified as either lymphoepithelioma, squamous cell, or anaplastic carcinoma, and were staged according to International Union Against Cancer (UICC) criteria. All patients were treated with curative intent using a 4 to 6 MeV linear accelerator to total doses ranging from 50 to 60 Gy in 4 to 6 weeks. The overall 5-year actuarial survival for all 55 patients was 44.4% (men, 41%; women, 52%). Survival by T stage was as follows: T1, 65%; T2, 51%; T3, 36%; and T4, 27%. Similarly, the 5 year survival rate declined as the bulk of nodal metastases increased: N0, 62%; N2, 50%; N3, 37%; and N1, 25%. Patients who had anaplastic carcinoma had a 5-year survival of 73%, those with lymphoepithelioma had a 60% survival, and those with squamous cell cancer (SCC) had a 30% survival. There was a statistically significant difference in 5-year survival between patients with SCC and those with nonkeratinizing histologies (P less than 0.05). In addition, there was a significant association between patients older than 40 years of age with SCC and patients younger than 40 years of age with nonkeratinizing malignancies (P less than 0.01). Of the 55 tumors successfully analyzed, 22 (40%) were diploid and 33 (60%) were aneuploid. The mean coefficient of variation (CV) of all 55 samples was 6.17%. There was no significant difference in 5-year survival between patients with diploid and those with aneuploid tumors (48% versus 42%). Furthermore, there was no statistically significant survival difference between aneuploid and diploid tumors within any one histologic subgroup. There was also no significant survival difference related to the DNA index. The results indicate that the extent of local tumor spread is still the most important prognostic factor for patients treated with radiotherapy for NPC. The data support the conclusion that patients with lymphoepithelioma and anaplastic carcinomas have a superior survival to patients with squamous cell carcinoma.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2208036 TI - The use of flow cytometry for the prognosis of stage II adjuvant treated breast cancer patients. AB - Characterization of breast cancer cells by histology, flow cytometry, and steroid receptors was performed on 197 Stage II breast node positive cancer patients given adjuvant chemotherapy, plus tamoxifen for patients with positive hormone receptors. Histologic and steroid receptor assays were performed using standard techniques; flow cytometric analysis was performed from paraffin-embedded blocks obtained from the primary tumor. Quality control studies on reproducibility, tissue heterogeneity, and analysis procedures have been included. Of the 197 patients studied, aneuploidy was found in 102 (52%); the median %S value was 8% with a range of 0.4% to 38%. Our results demonstrated that number of positive nodes, receptor status, and grade were of prognostic value. Cell cycle kinetic data were not of independent prognostic value in this series. However, ploidy could differentiate in prognosis in the receptor-negative subgroup. Patients with receptor-negative tumors had a significantly better overall survival if the tumor was diploid in nature. Cell kinetics was not significantly prognostic for either receptor subgroup, although patients with higher %S tended to have better relapse free and overall survival. This is in disagreement with other studies and may demonstrate that treatment has confounded our results and diminished the ability of flow cytometry data to help predict outcome. PMID- 2208037 TI - Immunocytochemical characterization of lung tumors in fine-needle aspiration. The use of cytokeratin monoclonal antibodies for the differential diagnosis of squamous cell carcinoma and adenocarcinoma. AB - In the current study, immunocytochemical typing of intermediate filaments was used for a differential diagnosis of human lung tumors from transthoracic fine needle aspiration biopsies (TFNAB). The authors have compared the cytologic diagnosis of 53 lung cancer cases with the immunofluorescence patterns obtained using a panel of monoclonal antibodies, five of which (KG 8.13, KM 4.62, Ks B.17, KS 8.12, KK 8.60) react with specific cytokeratin polypeptides and one with vimentin (VIM 13.2). Only in six of 23 samples cytologically diagnosed as squamous cell carcinoma did the immunocytochemical typing of cytokeratins (ICTC) confirm the cytologic diagnosis. In seven cases some of the tumor cells stained positively with antibody Ks B.17 specific for simple epithelial keratin (No: 18), suggesting the presence of some cells of glandular origin. In ten additional cases the ICTC was in conflict with the cytologic diagnosis of squamous cell carcinoma (i.e., antibodies Ks 8.12 and KK 8.60 were negative, and antibody Ks B.17, positive) supporting a diagnosis of adenocarcinoma. In 14 of 18 cases cytologically diagnosed as adenocarcinoma, the ICTC confirmed the diagnosis whereas in four cases additional presence of some squamous cells was noticed. The ICTC labeling of cases cytologically diagnosed as undifferentiated and large cell carcinomas was similar to that of the group of adenocarcinomas. Thus, the application of cytokeratin typing for TFNAB samples seems to provide a vital complementation to routine cytologic study, especially for cases cytologically diagnosed as squamous carcinoma. PMID- 2208038 TI - Comparison of the conventional method of lymph node staging with a comprehensive fat-clearing method for gastric adenocarcinoma. AB - Discrepant results in long-term survival between United States and Japanese patients with resectable gastric adenocarcinoma may result from more accurate staging in the Japanese series. The authors compared a comprehensive fat-clearing method with the conventional pathology method of lymph node sampling in 11 patients undergoing curative gastrectomy and extended lymphadenectomy at their institution. Comprehensive fat-clearing doubled total lymph node counts (P less than 0.01), identified smaller lymph nodes (P less than 0.001), and identified more histologically involved nodes of significantly smaller size (P less than 0.001). Comprehensive fat-clearing pathologically upstaged 29% of the authors' eligible specimens. Accurate pathologic staging is necessary when comparing Japanese and United States survival data for resectable gastric adenocarcinomas. PMID- 2208040 TI - Flow cytometric DNA-ploidy analysis of synchronously occurring multiple malignant tumors of the female genital tract. AB - In this study the authors applied flow cytometric DNA-ploidy analysis to multiple female genital tract malignant tumors in 43 patients, most of whom (n = 37) had bilateral ovarian cancer. An algorithm was developed for calculation of the likelihood ratio of the probabilities that measured DNA index differences between multiple tumor localizations within the same patient could be attributed to measurement variation or to true biologic DNA content differences. The results of this statistical analysis show that in 72% of the cases (31 of 43) this probability ratio exceeded 1. Because the probability that two independent tumors will have a near-identical aneuploid DNA content is very low, this finding supports a metastatic process rather than the occurrence of multiple primary tumors in these patients. Thus, flow cytometric DNA-ploidy analysis can be helpful in the identification of metastatic disease in patients with multiple female genital tract malignant tumors. PMID- 2208039 TI - Neuropeptide Y and neuron-specific enolase levels in benign and malignant pheochromocytomas. AB - Neuron-specific enolase (NSE) is the isoform of enolase, a glycolytic enzyme found in the neuroendocrine system. Neuropeptide Y (NPY) is a peptide recently discovered in the peripheral and central nervous systems. Serum NSE and plasma NPY levels have been reported to be increased in some patients with pheochromocytoma. The authors evaluated whether the measurement of these molecules could help to discriminate between benign and malignant forms of pheochromocytoma. The NSE levels were normal in all patients with benign pheochromocytoma (n = 13) and elevated in one half of those with malignant pheochromocytoma (n = 13). Plasma NPY levels were on the average significantly higher in the malignant (177.1 +/- 38.9 pmol/l, n = 16) than in the benign forms of the disease (15.7 +/- 389 pmol/l, n = 24). However, there was no difference in the percentage of patients with elevated NPY levels. These results show that determination of serum NSE may be useful for distinguishing between malignant and benign pheochromocytoma; the measurement of plasma NPY is not useful for differentiating the two kinds of tumors. PMID- 2208041 TI - Histologic subtypes and survival of Chinese patients with non-Hodgkin's lymphomas. AB - The histologic subtypes and survival of 840 Chinese patients with non-Hodgkin's lymphoma (NHL) were reviewed. All cases were classified according to the Rappaport and Kiel systems and the Working Formulation (WF). A low incidence of nodular/follicular lymphomas (12%) was observed. The most common histologic subtypes were diffuse histiocytic, diffuse centroblastic, and diffuse large cell lymphomas, according to Rappaport, Kiel, and the WF, respectively. A high proportion (24%) of the cases were unclassifiable, according to Kiel, because of the precise terms of the classification. The "favorable"-prognosis NHL, according to Rappaport, or the low-grade NHL, according to Kiel and the WF, had a more indolent clinical course. However, except for the nodular mixed (Rappaport) or follicular mixed (WF) lymphomas which appeared to behave like the more aggressive NHL, a plateau was not seen in the survival curves of our patients with other kinds of favorable-prognosis or low-grade NHL, indicating the lack of curative potential of these tumors. The lymphoplasmacytoid lymphoma, according to Kiel, also appeared to have a more aggressive clinical course. A plateau was seen in most of the other survival curves of patients with the more aggressive tumors, indicating the prospect of cure. However, the prognosis of the very aggressive tumors such as the diffuse lymphoblastic and diffuse small noncleaved cell lymphomas, according to the WF, remains very poor with a median survival of less than 10 months. PMID- 2208042 TI - Celebrating nursing. PMID- 2208043 TI - The need for distinction. PMID- 2208044 TI - Of intolerance. PMID- 2208045 TI - Education for nurse administrators. PMID- 2208046 TI - Promoting women's health. PMID- 2208047 TI - Guidelines for camp nurses in Ontario. PMID- 2208048 TI - [A bird's-eye view]. AB - Nurses, because of the nature of their work, often find it difficult to distance themselves emotionally from their patients. Thus, not surprisingly, they are subject to periods of depression. In this article the author presents a series of questions based on the cognitive therapy model to help nurses be more objective in other words, to encourage a bird's-eye view. PMID- 2208049 TI - [Assault in psychiatric centers]. AB - Psychiatric care workers must have the ability to predict aggressive behavior in their patients and the clinical skills to intervene in the event of patient assault. Though opinion is mixed on the practices of patient seclusion and restraint, they are sometimes necessary. Understanding aggressive behavior, however, is most important. PMID- 2208050 TI - Women and AIDS. PMID- 2208051 TI - National AIDS strategy announced. PMID- 2208052 TI - Molecular genetics of human bladder carcinomas. AB - Bladder cancer corresponds to a tumor type whose clinical behavior is difficult to predict. A better understanding of this pathology is expected from molecular genetics, which brings together cytogenetics and molecular biology. Therefore, we have tried to overview correlations between chromosome abnormalities and the presence, in the vicinity of the altered loci, of genes (oncogenes and others) that could be involved in bladder oncogenesis and/or tumor progression. In addition to oncogene activation by point mutations, gene amplification, or deregulation of gene expression, several cytogenetic as well as molecular evidences point to genetic deletions (existence of "tumor suppressor genes") being involved in those processes. PMID- 2208053 TI - Cytogenetic studies of human T-cell leukemia virus type I carriers. A family study. AB - Recently, the chromosome 14q11 anomaly has been reported to be specific to adult T-cell leukemia (ATL), and this anomaly has also been confirmed in the preleukemic state of adult T-cell leukemia (pre-ATL) patients. Because the cytogenetic abnormality at the stage of human T-cell leukemia virus type I (HTLV I) carrier remains uncertain, we performed cytogenetic studies of lymphocytes stimulated with phytohemagglutinin in three HTLV-I carriers and three non-HTLV-I carriers in an ATL family. As a result, in three HTLV-I carriers, four of 311 cells examined (1.3%) had chromosome 14q11 anomaly. However, in three non-HTLV-I carriers, none of 260 cells examined had chromosome 14q11 anomaly. These results suggest that chromosome 14q11 anomaly is already present at the stage of HTLV-I carrier and seems to be an important cytogenetic clue to the pathogenesis of ATL. PMID- 2208054 TI - Karyotypic characterization of established cell lines derived from a squamous cell carcinoma and an adenocarcinoma of human lung cancers. AB - Two non-small cell carcinoma cell lines from the major histopathologic groups of human lung cancers have been karyotyped: HS-24 was established from a squamous cell carcinoma, and SB-3 was obtained from a metastasis of a poorly differentiated adenocarcinoma. Endoreduplication is characteristic for both cell lines. Subsequent loss of chromosomes led finally to hypotetraploid karyotypes with modal chromosome numbers of 66-68 and 70-72 for HS-24 and SB-3, respectively. The structural analysis was performed by G- and C-banding. Stable overrepresentation of chromosomes 7, 8, 12, and 16 was found. Both cell lines developed a characteristic set of disomic and stable markers. Chromosomes involved in markers were 1, 2, 5, 6, 10, 11, 16, and 17. Consistent numerical and structural normality for chromosomes 4, 18, and 21 was observed. PMID- 2208055 TI - Cytogenetic analysis of dermatofibrosarcoma protuberans. AB - A case of dermatofibrosarcoma protuberans that occurred in an old burn scar over the anterior chest wall of a 46-year-old man is reported. Cytogenetic analysis of the tumor cells showed the presence of two abnormal clones: 47,XY, +8 and 48,XY, +8, +r. PMID- 2208056 TI - Reciprocal t(14;19)(q32.3;q13.1) in a patient with B-cell lymphoma. AB - A patient with B-cell lymphoma with a chromosome rearrangement of t(14;19)(q32.3;q13.1) is reported. This patient had leukemic features and an aggressive clinical course. The histopathologic diagnosis was malignant lymphoma, small noncleaved cell. Chromosome analysis of the cells from a cervical lymph node and peripheral blood showed a reciprocal translocation between chromosome 14 with a break at band q32.3 and chromosome 19 with a break at band q13.1, to which the bcl-3 gene has been mapped. Monoclonal rearrangement of the JH gene was detected by Southern blot analysis. However, we could not detect rearrangement of the bcl-3 gene. This case also had a t(2;8)(q13;q24.1), but the c-myc gene remained in its germline. This is the first case with the reciprocal t(14;19) and 8q24 chromosomal breakpoint in a B-cell lymphoid malignancy. PMID- 2208057 TI - Acute lymphoblastic leukemia in an XYY male. AB - A case of acute lymphoblastic leukemia (ALL) in a 16-year-old male with a 47,XYY karyotype is reported. This chromosome aneuploidy was found in both bone marrow (BM) cells and mitogen-stimulated lymphocytes. Immunologic profile of leukemic cells showed a null phenotype. To our knowledge, this is the fifth case reported in the literature. PMID- 2208058 TI - Differential expression of FRA16B in peripheral lymphocytes and bone marrow cells. AB - Expression of the rare fragile site FRA16B in chromosome band 16q22 was studied in bone marrow (BM) cells and peripheral blood lymphocytes (PBLs) from three unrelated subjects. Although FRA16B was detected only in PBLs from two healthy subjects who had been previously treated for non-Hodgkin's lymphoma (NHL), both cell types displayed FRA16B in a patient with chronic myelomonocytic leukemia (CMMoL). This variability in expression could be related to differences in the proliferative status of the cell populations or to differences in gene activity in the fragile site region. PMID- 2208059 TI - Translocation (X;12)(q27;q14) in a lipoma. AB - Cytogenetic analysis by short-term culture of a lipoma from the posterior neck region of a 63-year-old man showed a t(X;12)(q27;q14) as the sole chromosomal abnormality. Rearrangement of band 12q14 is nonrandom in lipomas, although its involvement with a sex chromosome has not been reported earlier. PMID- 2208060 TI - Establishment of a human T-acute lymphoblastic leukemia cell line with a (16;20) chromosome translocation. AB - A new T-cell line, Loucy, was established from the peripheral blood of a patient with T-cell acute lymphoblastic leukemia (T-ALL). The surface marker analysis of the cell line is OKT3+, OKT4+, THB4+, J5 +/-, OKT6-, TdT-, and HLA-DR-, indicating stage IV in T-cell lineage. Karyotype analysis revealed 45,X,5q ,t(16;20)(p12;q13). The translocation between chromosomes 16 and 20 has not been previously detected in ALL. This cell line may be of value in evaluating the role of t(16;20) in the etiology of T-ALL. PMID- 2208061 TI - Chromosomal analysis of colonic adenomatous polyps. AB - Chromosomal analysis of 25 colonic adenomatous polyps was performed by a direct method similar to that used in prenatal diagnosis of chromosomal aberration on chorionic villi. Fourteen lesions showed an abnormal karyotype. Two changes were recurrent: trisomy 7 (observed in eight cases) and trisomy 13 (observed in seven cases). No monosomy of the short arm of chromosome 17 was observed even at the level of two polyps with in situ carcinoma lesions. PMID- 2208063 TI - Chromosomal deletions in non-Hodgkin's malignant lymphomas. AB - The cytogenetics of 151 non-Hodgkin's malignant lymphomas (NHL) was reviewed to assess the incidence of monosomies and partial deletions. The incidence of complete or partial loss of chromosomes, possibly indicating putative tumor suppressor genes, was not significant. For chromosomes 3, 11, 13, 17, and 22, these frequencies were respectively 0%, 6.6%, 5.3%, 5.2%, and 6.6%. No specific association of deletions could be established. Three patients had a rearrangement of band 1q21 associated with deletion of chromosome 13. Finally, the most frequent chromosome segment loss in NHL involves the long arm of chromosome 6 (15.2%). PMID- 2208062 TI - On the significance of trisomy 7 and sex chromosome loss in renal cell carcinoma. AB - Cytogenetic analysis of 30 renal cell carcinomas showed 3p aberrations in nine tumors, trisomy 7 in 17 tumors, and clonal loss of one sex chromosome in 14 tumors. The 3p aberrations and trisomy 7 were present in the same clone in two tumors and in separate clones in three tumors. Loss of one sex chromosome was present together with 3p aberrations in the same clone in one tumor and occurred in seemingly unrelated clones in two tumors. It occurred as the sole change in five tumors. Clones with trisomy 7 as the only change were present in six tumors. Trisomy 7 and loss of one sex chromosome were present in separate clones in four tumors and in the same clone in one tumor. Because +7 and -X/-Y were thus rarely present together with clonal structural abnormalities, in particular 3p changes, our findings make it highly unlikely that loss of one sex chromosome or trisomy 7 represents a primary change in renal cell carcinoma. We instead suggest that there is a tendency for normal kidney cells to lose an X or a Y chromosome and also to gain an extra copy of chromosome 7. This tendency is retained by renal carcinoma cells; therefore, trisomy 7 and sex chromosome loss should not be viewed as tumor-specific abnormalities in this context. Whether these simple numerical aberrations reflect in vivo mosaicism or are acquired in vitro remains unresolved. PMID- 2208064 TI - Isochromosome (17q) in Ph-negative chronic myelocytic leukemia. PMID- 2208065 TI - Supernumerary ring chromosome as the sole cytogenetic abnormality in a dermatofibrosarcoma protuberans. PMID- 2208066 TI - Translocation (3;13) as a primary change in an unusual case of acute nonlymphocytic leukemia, type M5. PMID- 2208067 TI - Cytogenetic studies of basal cell carcinomas. PMID- 2208068 TI - The cytotoxic effect of ajoene, a natural product from garlic, investigated with different cell lines. AB - The sulfur-containing compound ajoene (4,5,9-trithiadodeca-1,6,11-triene-9-oxide) which arises from alliin, a cysteine derivative stored in garlic bulbs, was produced synthetically by decomposition of allicin. Its cytotoxic effect was tested using human primary fibroblasts (FS4), a permanent, non-tumorgenic cell line derived from baby hamster kidney cells (BHK21) and a tumorgenic lymphoid cell line derived from a Burkitt lymphoma (BJA-B). The cytotoxic action was in the range 2-50 micrograms/ml depending on the cell density. ED50 values, estimated on the basis of fmol ajoene/cell, revealed slightly higher doses for the primary cell (FS4) than the permanent line (BHK), whereas the tumorgenic BJA B cells were most sensitive. PMID- 2208070 TI - Effect of sex and age on rectal cell renewal in humans. AB - We evaluated the influence of age and sex on rectal cell proliferation of 69 hospital controls and 66 patients with colorectal adenomas, by means of incubation of rectal biopsies with tritiated thymidine and autoradiography. In particular, we evaluated the labeling frequency in the upper 40% of rectal crypts (0 h), actually considered as a reliable kinetic marker of colon cancer risk. A direct correlation between 0h and age was found in control subjects (P less than 0.02) but not in adenomas patients (P = NS). Moreover, control subjects over 65 years of age showed a shift of the proliferative compartment similar to that observed in the adenomas group. After adjusting for the age, we did not observe any significant effect of the sex of patients or controls on their cell kinetics parameters. Our results are in agreement with those previously reported on smaller series and with epidemiological studies which indicate a high risk for developing colorectal neoplasia in the elderly subjects. PMID- 2208069 TI - The concentration of glucose in the culture medium determines the effect of suramin on the growth and differentiation of the human colonic adenocarcinoma cell clone HT29-D4. AB - Suramin, a drug currently used for advanced malignancy, induces the differentiation of the human colonic adenocarcinoma cell clone HT29-D4 and this process is correlated with a decreased glycolytic activity. We investigated the effects of suramin on HT29-D4 cells in the presence of various glucose concentrations. The main result of this study is that suramin has only an effect on HT29-D4 cell growth and differentiation when the concentration of glucose is above 10 mM. Therefore the efficiency of suramin as an anticancer drug may be greater on poorly differentiated tumoral cells with a high proliferative capacity. PMID- 2208071 TI - Comparative study of the therapeutic effect of photoactivated hematoporphyrin derivative and aluminum disulfonated phthalocyanines on tumor bearing mice. AB - Although the hematoporphyrin derivative (Hpd) is one of the most studied photosensitisers for photodynamic therapy (PDT), it is far from ideal. Therefore, many laboratories have been investigating a new group of sensitisers, the phthalocyanines. Particularly, in our laboratory we decided to study the aluminum disulfonated phthalocyanines (AlS2PC). They are chemically stable, readily soluble in water and have a strong absorption in the red part of the spectrum at 675 nm. Mice bearing the MS-2 fibrosarcoma treated with 5 mg/kg of AlS2PC survived indefinitely also using a low laser power of 100 mW/cm2 X 10' of exposure time, in contrast to experiments carried out with Hpd where the optical therapeutic laser power was 400 mW/cm2 X 10' and the dose of Hpd was 25 mg/kg. Furthermore, treatment of mice bearing the highly metastatic tumor, B16 melanoma, with 5 mg/kg of AlS2PC and laser light (100 mW/cm2 X 10'), significantly prolonged the survival time in respect to mice treated with 25 mg/kg of Hpd and laser light (400 mW/cm2 X 10'). PMID- 2208072 TI - Localization of potent photosensitizers in human tumor LOX by means of laser scanning microscopy. AB - By means of laser scanning fluorescence microscopy the intratumoral localization patterns of several photosensitizers in LOX tumors in nude mice were studied. Lipophilic dyes such as P-II (Photofrin II), 3-THPP tetra(3 hydroxyphenyl)porphin, TPPS1 (tetraphenylporphine monosulfonate), TPPS2a (tetraphenylporphine disulfonates with the sulfonate groups on adjacent rings), A1PCS1 (aluminium phthalocyanine monosulfonate) and A1PCS2 (aluminium phthalocyanine disulfonates) localized mainly in tumor cells. The fluorescence intensity of these dyes increased from 4 h to 48 h post-injection and the fluorescence was still observable 120 h post-injection. The more hydrophilic dyes such as TPPS2o (tetraphenylporphine disulfonates with the sulfonates groups on opposite rings), TPPS3 (tetraphenylporphine trisulfoantes), TPPS4 (tetraphenylporphine tetrasulfonates), A1PCS3 (aluminium phthalocyanine trisulfonates) and A1PCS4 (aluminium phthalocyanine tetrasulfonates) localized mainly extracellularly in the tumorous stroma. The fluorescence intensity of these dyes decreased from 4 h to 48 h post-injection. 120 h post-injection no significant fluorescence of these dyes could be seen in the tumors. The data are discussed in relation to what is known about the in vivo photosensitizing efficiency of some of the dyes. PMID- 2208073 TI - Anti-tumor-promoting activity of derivatives of abieslactone, a natural triterpenoid isolated from several Abies genus. AB - Abiesenonic acid methyl ester (AVB-I acid methyl ester), a triterpenoid compound prepared from abieslactone, suppressed tumor promoter-induced phenomena in vitro and in vivo; i.e., AVB-I acid methyl ester inhibited 12-o-tetradecanoylphorbol-13 acetate (TPA)-stimulated 32Pi-incorporation into phospholipids of cultured cells and the promoting action of TPA on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene. PMID- 2208074 TI - Localization and production of proteoglycans by HT1080 cell lines with altered N ras expression. AB - The alterations in the production of proteoglycans in relation to the expression of the malignant phenotype - controlled by the level of expression of activated N ras gene - was studied in HT1080 human fibrosarcoma cells and in its revertant variants rev.1c and rev.10a. A decreased production of radiolabelled PGs - especially HSPGs - was observed in HT1080 cells, compared to the revertant lines. By immunofluorescence, the HSPG epitopes were localized mainly into the putative endoplasmic reticulum and/or Golgi zone in HT1080 cells, and to the diffuse cytoplasmic and membrane localization in the revertant lines. It is suggested, that the altered expression of PGs represents an important aspect of the transformed phenotype of HT1080 fibrosarcoma cells. PMID- 2208075 TI - Promoting action of prolactin released from a grafted transplantable pituitary tumor (MtT/F84) on rat prostate carcinogenesis. AB - The potential modifying effects of high prolactinemia on rat prostate carcinogenesis was investigated. Male F344 rats were treated at 5 times of 5-week intervals with s.c. injections of 3,2'-dimethyl-4-aminobiphenyl (DMAB), each injection following 3 weeks pretreatment with dietary ethinyl estradiol. After completion of the carcinogen administration stage, rats received multiple s.c. transplantations of a prolactin producing transplantable pituitary tumor, MtT/F84 until sacrifice at week 51. The effects of additional or single treatment with bromocriptine, a prolactin suppressing agent, were also investigated. The body, liver and kidney but prostate weights were significantly increased in the groups given MtT/F84. Although the development of prostate carcinomas was not affected by the observed hyperprolactinemia, the incidences of atypical hyperplasia of both ventral and lateral prostate were significantly enhanced. The findings thus indicate that prolactin may have promoting potential for prostate carcinogenesis. PMID- 2208076 TI - Glucose-6-phosphate dehydrogenase (G6PD) activity in tumoral tissues of G6PD deficient subjects affected by larynx carcinoma. AB - The activity of glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the hexose monophosphate (HMP) shunt pathway, was measured in both normal and tumoral larynx tissues from normal and G6PD deficient subjects. Significant increases of this enzymatic activity were found in tumoral tissues of both normal and G6PD deficient subjects, who were characterized by very low levels of G6PD activity in erythrocytes as well as in larynx tissue. PMID- 2208077 TI - Effects of the plant flavonoid baohuoside-1 on cancer cells in vitro. AB - The novel plant flavonoid 3,5,7,-trihydroxy-4'-methoxyl-8'-prenylflavone-3-O alpha-L-rham nopranoxide (designated baohuoside-1) was shown to have cytotoxic and cytostatic effects on 6 cancer cell-lines, by means of microscopy, 51Cr release and growth inhibition. The IC50 on the cells tested ranged from 2.8 to 7.5 micrograms/ml. At tumouricidal concentrations, inhibition of DNA and RNA synthesis, but not protein synthesis was observed. PMID- 2208078 TI - Comparison of free and liposome encapsulated doxorubicin tumor drug uptake and antitumor efficacy in the SC115 murine mammary tumor. AB - Tumor drug uptake and antitumor efficacy of free and liposomal doxorubicin (DOX) were determined in the SC115 Shionogi mouse mammary tumor. Liposomal DOX systems were prepared by pH gradient-driven drug encapsulation in 170 nm egg phosphatidylcholine/cholesterol (55:45, mol ratio) vesicles. Intravenous injection of free DOX at 6.5 mg/kg, the maximum tolerated dose for free drug in the multiple dose therapy regimen, resulted in tumor-associated drug levels of 2.0 micrograms/g tissue at 1 h which remained constant over 24 h. Liposomal DOX injected at 6.5 mg/kg led to an accumulation of drug in the tumor from 2.6 micrograms/g tissue to 5.5 micrograms/g tissue between 1 h and 24 h, respectively. Increasing the dose of liposomal DOX to 13.0 mg/kg increased tumor drug uptake levels to 5.7 micrograms/g and 10.2 micrograms/g tissue at 1 h and 24 h, respectively. Administration of free or liposome encapsulated DOX every 7 days for 3 weeks resulted in a dose-dependent decrease in tumor growth rate. However, liposomal DOX injected at 6.5 mg/kg exhibited enhanced tumor growth inhibition compared to an equivalent dose of free drug. Further, the ability to administer increased doses of the less toxic liposomal DOX not only resulted in a greater inhibition of tumor growth but also significantly reduced tumor weight. Tumors weighing as much as 5 g were diminished to less than 0.5 g upon treatment with liposomal DOX at a dose of 13 mg/kg. In addition, groups receiving the highest liposomal DOX dose exhibited 25% complete tumor regression which persisted over the 50-day study period. These results demonstrate the ability of appropriately designed liposomal DOX systems to significantly enhance the delivery and retention of drug at solid tumor sites, resulting in increased therapeutic activity. PMID- 2208079 TI - Carcinogenic activity of a carbamate fungicide, mancozeb on mouse skin. AB - Mancozeb, a polymeric complex of ethylene bis (dithiocarbamate) manganese with zinc salt is a protective fungicide. In the present study complete carcinogenic activity of mancozeb, has been observed following topical application on dorsal mouse skin. Female Swiss albino mice were exposed to mancozeb at a dose of 100 mg/kg body weight dissolved in 100 microliters dimethyl sulfoxide 3 times per week. Development of tumours was observed after 31 weeks (217 days) of mancozeb application. A high rate of mortality was observed after 54 weeks (378 days) of mancozeb application due to its toxicity and the study was terminated after 60 weeks. On histological examination, these tumours were found mostly to be benign in nature, e.g., squamous cell papillomas and keratoacanthomas. PMID- 2208080 TI - In vivo binding of 3,3'-dichlorobenzidine to rat and mouse tissue DNA. AB - The kinetics of total DNA adducts were compared in the liver, bladder epithelium and small intestinal epithelium of rats and mice following a single oral dose (100 mg/kg) of 3,3'-dichlorobenzidine [( 14C]DCB). Peak DNA binding (expressed as pmol DCB bound/mg DNA) in rat tissues was 153.5, 144.8 and 36.9 in the intestine, bladder and liver, respectively, whereas in mouse tissues, the binding was 72.5, 58.2 and 55.8, respectively. In either species, the half-life of the DNA adducts in the liver (13.5 and 13.8 days in rats and mice, respectively) was comparable to that in the bladder epithelium (14.8 and 12.7 days in rats and mice, respectively) but longer than that in the intestinal epithelium (5.9 and 4.7 days in rats and mice, respectively). Peak total DCB binding in hepatic but not intestinal or bladder epithelial DNA correlated positively with total urinary DCB metabolites. In vitro, mouse hepatic S9 was 57% more active in catalyzing the formation of DNA-binding derivatives of DCB, in parallel with the higher in in vivo maximum hepatic DNA binding in mice than in rats. Thus, a single oral dose of DCB in rats and mice leads to extensive binding of the chemical to tissue DNA, with the rate of removal of the adducts not differing between target and non target tissues. PMID- 2208081 TI - Low level amplification of c-sis and c-myc in a spontaneous osteosarcoma model. AB - Canine and human osteosarcoma are very similar clinically, radiologically and pathologically. DNA extracted from canine osteosarcomas (n = 9) and normal canine control tissues (n = 17) was examined for amplification of the c-sis, c-myc, N myc and c-H-ras protooncogenes. Statistically significant amplification of the c sis and c-myc protooncogenes was evident in the tumor tissues as compared to the normal control tissues (P less than 0.05). DNA and total cellular RNA from cultured canine and human osteosarcoma and fibroblast cell lines were examined for amplification or enhanced expression of c-sis and c-myc. Very low levels of c myc and c-sis DNA amplification were noted in canine osteosarcoma cells as compared to canine fibroblasts. Immunostaining of sections of human and canine osteosarcoma for the sis gene product, PDGF B, showed similar levels and patterns of expression in both populations of tumors. PMID- 2208082 TI - Consumption of methylxanthine-containing beverages and the risk of breast cancer. AB - The idea that caffeine might be involved in the etiology of breast disease was first proposed by Minton et al. in 1979. Since that time, numerous experimental and epidemiologic studies evaluating the relationship between methylxanthines and breast disease have been conducted. Results from studies on benign breast disease have been inconsistent, with some investigators observing a positive association and others no association. However, all but one of the studies which have examined methylxanthine intake and malignant breast disease have concluded that methylxanthines do not play a role in the development of this cancer. Although various methodologies were employed and different populations were evaluated, results were consistently negative. Thus, there appears to be no evidence of an association between coffee and other methylxanthine-containing beverages and breast cancer. PMID- 2208083 TI - Involvement of urine in epithelial-stromal interactions in urinary bladder carcinogenesis. AB - The role of urine in epithelial-stromal interactions in urinary bladder carcinogenesis was investigated using the 'Stroma' bladder model established in our laboratory. Rats treated with 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BHBN) in drinking water for 4 weeks or age-matched untreated rats served as donors of bladders with denuded epithelium ('stroma' bladders), which were resurfaced 4 days later with urothelial cells from rats treated with 0.05% BHBN for 4 weeks. Subsequently, the transplants received weekly injections of normal rat urine or saline. In the urine-free environment, cell implants developed hyperplastic changes but few tumor formations with no significant difference between the two types of 'stroma' bladder. In contrast, urine instillation stimulated neoplastic growth, and tumor-enhancing effect was significantly accelerated in the BHBN-treated 'stroma' bladder group as compared to the control group. These results suggest that epithelial-stromal interactions are altered in such a way that bladder carcinogenesis is enhanced by prior exposure of the bladder stroma to carcinogen and subsequent urine contact. PMID- 2208084 TI - Potential use of D-glucaric acid derivatives in cancer prevention. AB - There is now growing evidence from animal models for the possible control of different stages of the carcinogenic process by the beta-glucuronidase inhibitor D-glucaro-1,4-lactone and its precursors such as D-glucaric acid salts, D glucarates. D-Glucaric acid is a natural, non-toxic compound produced in small amounts by mammals, including humans. It was recently found in some vegetables and fruits. D-Glucaro-1,4-lactone and D-glucarate exhibit potent antiproliferative properties in vivo. Some human subpopulations could have reduced risk of cancer development by ingesting food rich in D-glucaric acid or self-medication with D-glucarates alone or in combination with other chemopreventive agents. PMID- 2208085 TI - 2-Hydroxyethylnitrosourea induction of B cell lymphoma in female Swiss mice. AB - Groups of 30 adult Swiss mice of both sexes from the Eppley Institute breeding colony were treated with 37.5 or 75 mg 2-hydroxyethylnitrosourea (HENU)/l citrate buffer, given as drinking water on 4 days/week from 6-8 weeks of age for life. A third group of mice was untreated. Incidences of generalized B cell lymphoma (BCL) were 67% (males) and 87% (females) for the higher dose of the nitrosourea, 29% (males) and 79% (females) for the lower dose and 0% (males) and 7% (females) for the untreated mice. Tumor latencies were 23 weeks (high dose) and 27 weeks (low dose) in the females and 6-7 weeks longer in the males. A B-cell origin of the lymphomas was indicated by the pathology and tumor distribution and was confirmed in 4 mice by immunophenotyping and in 6 mice by probes for gene rearrangements. This system may be an effective means of inducing B cell lymphoma with a carcinogen. PMID- 2208086 TI - Diffusion of insulin-like growth factor 1 in human breast cancer explants. AB - Tumor explants, from 15 patients with primary breast cancers, were incubated in organ culture medium containing [125I]IGF1. Measurements of explant radioactivity were performed in order to evaluate IGF1 uptake and release as a function of time, medium concentration and patient, in tumors with low IGF1 receptor levels. Uptake and release were governed by a passive diffusion mechanism and could be well described by a pharmacokinetic-like model. The rate of uptake depended on patient but affinity of IGF1 for the tumor tissue was always higher than affinity for the medium. Moreover the rate of uptake was faster than IGF1 clearance in man. From these results it can be extrapolated that the IGF1 circulating level must strongly influence the tumor content, independently of the receptor level. In the same way, IGF1 analogs could be administered via blood injection and the administration could be monitored by the above described pharmacokinetic model. PMID- 2208087 TI - The kinetics of 1-nitropyrene and 3-nitrofluoranthene metabolism using bovine liver xanthine oxidase. AB - The cytosolic molybdoflavoprotein xanthine oxidase has been shown to catalyze the reduction of exocyclic nitro groups to the corresponding nitroso, hydroxylamino and amino derivatives for a wide variety of xenobiotics including the nitrated polycyclic aromatic hydrocarbons 1-nitropyrene and 3-nitrofluoranthene. Using commercially available bovine liver xanthine oxidase, we have studied the kinetics of the metabolism of 1-nitropyrene and 3-nitrofluoranthene. The nitroreduction of these nitro compounds in the presence of xanthine oxidase is dependent on the presence of hypoxanthine or xanthine and the absence of oxygen. This nitroreduction is independent of added flavins (FMN and FAD), unlike the related molybdoflavoprotein aldehyde oxidase. Xanthine oxidase has a Km of 0.7 microM and Vmax of 0.06 nmol/min per unit enzyme for 1-nitropyrene and a Km of 8.6 microM and Vmax of 0.7 nmol/min per unit enzyme for 3-nitrofluoranthene. The importance of these kinetic constants in evaluating the cytosolic metabolism of 1 nitropyrene and 3-nitrofluoranthene are discussed. PMID- 2208088 TI - Response of fibroblast cultures from ataxia-telangiectasia patients to oxidative stress. AB - The object of this study was to determine whether ataxia-telangiectasia (AT) cells are more sensitive than normal cells to reduced oxygen species generated either during normal cell processes or resulting from metabolism of xenoblotics. To test this hypothesis four AT and four normal fibroblast cultures were exposed to hydrogen peroxide (H2O2) and the induction of micronucleated cells was assayed. AT cultures responded to the H2O2 treatment with a greater increase in micronucleus frequencies than that observed in normal cultures (P less than 0.01). At time course study showed that an elevation in micronucleus frequencies occurred earlier in AT cultures (significant increase by 1.5 h after treatment) than in normal cultures, possibly indicating a G2-phase sensitivity of AT cells to H2O2. The addition of an aqueous extract of areca nut to the cultures, as an example of exogenous stress, induced a greater frequency of micronucleated cells in AT cultures than in the normal cultures. These results suggest that the AT syndrome may serve as a model for investigating the role of reduced oxygen species in cancer. PMID- 2208089 TI - Transforming growth factor-beta 1 stimulates proliferation of Morris hepatoma cells in serum-free soft agar culture system supplemented with EGF and insulin. AB - The anchorage-independent growth of Morris hepatoma 7777 (MH) cells in serum-free medium was examined. The influence of insulin, epidermal growth factor and transforming growth factor beta 1 (TGF-beta 1) on [3H]thymidine incorporation and colony formation of the investigated cells was described. Contrary to normal rat hepatocytes TGF-beta 1 plus EGF and insulin were found to stimulate MH cells proliferation in presented conditions. A simple, chemically-defined culture system suitable for research on mitogenic peptides was proposed. PMID- 2208090 TI - Increased biopterin production in rats with tumors induced by radon inhalation and benzonaphthoflavone administration. AB - Serial determinations of urinary biopterin were performed in rats during the development of lung tumors induced by radon inhalation and 5,6-benzonaphtoflavone administration. A striking increase in biopterin levels was observed in animals which developed single or multiple epidermoid carcinoma of the lung and this increase occurred several weeks before tumors could be detected radiographically. PMID- 2208091 TI - N-nitroso compounds and their precursors in Brassica oleracea. AB - In the present study, Brassica a dried green vegetable from Kashmir, which is a major constituent of the local diet, was analysed for nitrosatable aliphatic amines, N-nitrosamines prior to and after nitrosation) and alkylating activity due to N-nitrosamides following nitrosation. The cooked vegetable contained 11 micrograms/kg nitrosodimethylamine and 21 micrograms/kg nitrosopyrrolidine. Nitrosation under chemical conditions yielded 1200 micrograms/kg N methylnitrosourea. PMID- 2208092 TI - Lack of enhancing effects of fenvalerate and esfenvalerate on induction of preneoplastic glutathione S-transferase placental form positive liver cell foci in rats. AB - The modifying effects of fenvalerate and esfenvalerate administration on liver carcinogenesis were investigated in male F344/DuCrj rats initially treated with N nitrosodiethylamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats were given fenvalerate at dietary levels of 1500, 500, 150, 50 and 15 parts per million (ppm), esfenvalerate at 500 ppm, or 2 acetylamino-fluorene (2-AAF) at 200 ppm and sodium phenobarbital (PB) at 500 ppm as positive controls for 6 weeks. At week 3 following DEN administration, all animals were subjected to partial hepatectomy. Prominent neurologic signs and moderate retardation of body weight were observed in the groups given 1500 ppm fenvalerate and 500 ppm esfenvalerate, although no adverse effects on survival were evident. While statistically significant increases in relative liver weights were noted in rats given fenvalerate at doses of 1500 or 500 ppm, no toxic hepatocyte lesions were found. Neither fenvalerate nor esfenvalerate significantly increased the numbers or areas of glutathione S-transferase placental form (GST-P) positive liver cell foci observed after DEN initiation, in clear contrast to the positive controls, 2-AAF and PB. The results thus demonstrated that fenvalerate and esfenvalerate are non-toxic for rat hepatocytes and lack modifying potential for liver carcinogenesis in our medium-term bioassay system. PMID- 2208093 TI - Evaluation of immunohistochemical staining of breast tissue by an oestrogen regulated protein, 24K according to epidemiological and radiological breast cancer risk criteria. AB - The staining characteristics of monoclonal antibodies (MAb) are often determined on small numbers of biopsies. The true staining profile can only properly be determined when large numbers of biopsies are stained. We have examined the staining profile of 24K MAb on 146 benign breast biopsies. The staining characteristics were then grouped according to whether the patients were at high or low risk of breast cancer by current epidemiological or radiological risk criteria. This was done to detect whether 24K MAb could be used as a marker of cancer risk. Only Wolfe coded risk criteria showed staining differences between the two risk categories. Cytoplasmic staining was more common in the low risk Wolfe coded groups (P = 0.03, Fisher's exact test). We recommend that further studies be undertaken to evaluate the role of 24K MAb as a marker of cancer risk. PMID- 2208094 TI - Alterations in splenic natural killer cell activity induced by the Shionogi mouse mammary tumor. AB - We have previously demonstrated that differential housing conditions alter the growth rate of the Shionogi mouse mammary carcinoma (SC115). The present study was undertaken to determine if natural killer (NK) cells are involved in mediating the effects of differential housing on SC115 tumour growth rate. Splenic NK cell activity was assayed at 24 h, 3 days and 1 week post-injection in both tumour- and vehicle-injected animals. Significant stimulation of splenic NK cell activity occurred 3 days post-injection of SC115 cells. However, no correlation was observed between the level of splenic NK cell activity and tumour growth rate induced by housing condition. We conclude that either splenic NK cell activity does not accurately reflect NK cell activity at the tumour site or that NK cells are not a significant regulator of the differential tumour growth rates seen in this model. PMID- 2208095 TI - Assessment of genotoxicity of nicotine employing in vitro mammalian test system. AB - Genotoxicity of nicotine was evaluated employing Chinese hamster ovary (CHO) cells. Two cytogenetic endpoints, viz. frequency of sister chromatid exchange (SCE) and chromosome aberration (CA) were considered. Nicotine was found to induce CA and SCE frequency in a dose and duration dependent manner. Statistically significant elevations in CA frequency were observed only with higher concentrations of nicotine, whereas, SCE frequencies were increased significantly by all the doses utilized. It was genotoxic at the concentration, comparable to the saliva levels of nicotine achieved during tobacco chewing. The results obtained by continuous and pulse treatments with nicotine explain the harmful effects of chronic tobacco consumption. PMID- 2208096 TI - A model for improving cancer patient education. AB - Adjustment to cancer requires modification of behavior that may be aided through patient education. Numerous programs have been developed to meet this need; however, studies show that even after being taught, patients are not well informed. It seems that the process of educating cancer patients needs to be improved. Authors suggest a progression of psychosocial stages of adjustment to serious illness during which specific behaviors are exhibited and coping mechanisms utilized. Understanding the nature of this process forms the basis for effective patient education since theories of adaptation describe behaviors that impact on motivation to learn, information required, and teaching methodology. Failure to attend to this variable of emotional response to the disease can prevent learning. This article integrates the theories of Weisman, Crate, Engle, and Kubler-Ross into an educational model for the cancer patient consisting of six periods. The model suggests nursing approaches, educational topics, and teaching strategies based on the patient's behavioral responses. Use of this model can improve teaching effectiveness in clinical practice by ensuring that the patient is ready to learn prior to teaching and by utilizing teaching strategies appropriate to the educational period. It can further be used as a tool to teach students of nursing how to use the stages of adjustment to chronic illness when planning patient teaching. PMID- 2208097 TI - A stepwise approach to developing and maintaining an oncology multidisciplinary conference. AB - In recent years, there has been a shift in cancer treatment sites, from university-based to community settings. Approximately 85% of cancer patients are now diagnosed and treated in community hospitals. This change has been accompanied by an expansion of oncology services and specialists. One method that has increased communication and knowledge among departments providing oncology services, has been the Oncology Multidisciplinary Conference. This paper provides practical guidelines for establishing and maintaining such a group in a community hospital. PMID- 2208098 TI - Measurement of stress in clinical nursing. AB - The Nurse Stress Checklist was developed to measure stress in clinical nursing as a multidimensional construct. The instrument was formulated within a transactional model of stress. The items were derived from five domains thought to contribute to nurse stress in clinical settings and were organized into a questionnaire. Holmes Schedule of Recent Events was included as a validity measure. The instrument was tested on 104 staff nurses working in three institutions in an urban community. Exploratory factor analysis was applied to the 74 items presented to subjects in Likert-type format. Five factors were derived and subjected to psychometric evaluation. Internal consistency reliability for the five factors was good, ranging from 0.80 to 0.91. Means and measures of dispersion supported the potential of the five subscales to discriminate among respondents on the attributes being measured. Intercorrelations of the factors provided evidence of the distinctiveness of the five components of stress, although factor loadings showed some overlap between Personal Reactions and Work Concerns and Work Concerns and Work Completion Concerns. Validity of the factors also was supported by correlations with Holmes' Schedule of Recent Events. Content validity was supported by comparison of these results with findings of other investigators. Limitations of the results are discussed, and recommendations for future work on the instrument are offered. PMID- 2208099 TI - The shining stranger. Nurse-family spiritual relationship. AB - The purpose of this study was to uncover, through nurses' and families' descriptions of their hospice experience, the elements comprising the nurse family spiritual relationship. Findings were synthesized into five themes: nurses' ways of being, nurses' ways of doing, nurses' ways of knowing, ways of receiving and giving, and ways of welcoming a stranger. Results indicated that the nurse-family spiritual relationship is mutual and dialogic, and fosters spiritual growth for both nurses and families. Implications for nursing practice and theory are discussed. PMID- 2208100 TI - Self-assessed learning needs of oncology nurses caring for individuals with HIV related disorders. A national survey. AB - A national survey of 10% of the members of the Oncology Nursing Society (ONS) was conducted to determine the knowledge and experience of oncology nurses caring for individuals with HIV-related disorders. This information was to serve as the framework for developing subsequent education and preparation of oncology nurses. A questionnaire containing 109 questions was mailed to 1,006 members of the ONS. Response rate was 70% (N = 693). Fifty-five of the 109 questions assessed clinical knowledge, experience, and care planning for adults. Additional questions elicited information about staff attitudes, problems in care delivery, priorities in nursing administration and research, and nurses' preferred methods of instruction. Results showed that oncology nurses are experienced in certain areas of importance to patients with AIDS but have educational and experiential deficits in the disease specifics associated with HIV-related disorders and in the nursing care of adults with multisystem involvement and in their treatment. Validity and reliability of this questionnaire were established (alpha = 0.93 0.97). Readers are encouraged to adapt this questionnaire to assess the learning needs of nurses in all specialty groups, and to develop appropriate educational programs to prepare nurses to provide care for this patient population. PMID- 2208101 TI - Programmed instruction: cancer pain. PMID- 2208102 TI - Epidemiology, basic science, and the prevention of cancer: implications for the future. PMID- 2208103 TI - Glutathione S-transferases: role in alkylating agent resistance and possible target for modulation chemotherapy--a review. PMID- 2208104 TI - An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: effects on growth and craniofacial proportion. AB - Many long term survivors of childhood acute lymphoblastic leukemia have short stature, as well as craniofacial and dental abnormalities, as side effects of central nervous system prophylactic therapy. An animal model is presented to assess these adverse effects on growth. Cranial irradiation (1000 cGy) with and without prednisolone (18 mg/kg i.p.) and methotrexate (2 mg/kg i.p.) was administered to 17- and 18-day-old Sprague-Dawley male and female rats. Animals were weighed 3 times/week. Final body weight and body length were measured at 150 days of age. Femur length and craniofacial dimensions were measured directly from the bones, using calipers. For all exposed groups there was a permanent suppression of weight gain with no catch-up growth or normal adolescent growth spurt. Body length was reduced for all treated groups, as were the ratios of body weight to body length and cranial length to body length. Animals subjected to cranial irradiation exhibited microcephaly, whereas those who received a combination of radiation and chemotherapy demonstrated altered craniofacial proportions in addition to microcephaly. Changes in growth patterns and skeletal proportions exhibited sexually dimorphic characteristics. The results indicate that cranial irradiation is a major factor in the growth failure in exposed rats, but chemotherapeutic agents contribute significantly to the outcome of growth and craniofacial dimensions. PMID- 2208106 TI - Human homologue of Moloney leukemia virus integration-4 locus (MLVI-4), located 20 kilobases 3' of the myc gene, is rearranged in multiple myelomas. AB - The structure of the c-myc locus and the flanking chromosomal region was investigated by Southern blot analysis of DNA from bone marrow aspirates from 42 patients with multiple myeloma. The main abnormality detected was the rearrangement of the MLVI-4 locus, 20 kilobases 3' of c-myc, which was observed in seven cases (16%). Two of these rearrangements were detected at the time of the initial diagnosis, four during treatment, and one at relapse, and their presence correlated with unresponsiveness to therapy. The MLVI-4 locus represents the human homologue of the Moloney leukemia virus integration-4 locus (Mlvi-4), a common region for provirus integration in Moloney murine leukemia virus-induced T cell lymphomas in rodents. Provirus integration in this locus activates c-myc, and two additional genes, Mlvi-4 and Mlvi-1. The c-myc gene was rearranged in one patient; mutations involving the first exon of c-myc, frequently detected by altered restriction enzyme recognition sites in Burkitt's lymphomas, were not observed in these myelomas. PMID- 2208105 TI - An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: effects on behavior. AB - Central nervous system prophylactic therapy used in the treatment of acute lymphoblastic leukemia can reduce intelligence quotient scores and impair memory and attention in children. Cranial irradiation, intrathecal methotrexate, and steroids are commonly utilized in acute lymphoblastic leukemia therapy. How they induce neurotoxicity is unknown. This study employs an animal model to explore the induction of neurotoxicity. Male and female Sprague-Dawley rats at 17 and 18 days of age were administered 18 mg/kg prednisolone, 2 mg/kg methotrexate, and 1000 cGy cranial irradiation. Another 18-day-old group was administered 1000 cGy cranial irradiation but no drugs. Matching controls received saline and/or a sham exposure to radiation. All animals at 6 weeks and 4 months of age were tested for alterations in spontaneous behavior. A computer pattern recognition system automatically recorded and classified individual behavioral acts displayed during exploration of a novel environment. Measures of behavioral initiations, total time, and time structure were used to compare treated and control animals. A permanent sex-specific change in the time structure of behavior was induced by the prednisolone, methotrexate, and radiation treatment but not by radiation alone. Unlike hyperactivity, the effect consisted of abnormal clustering and dispersion of acts in a pattern indicative of disrupted development of sexually dimorphic behavior. This study demonstrates the feasibility of an animal model delineating the agent/agents responsible for the neurotoxicity of central nervous system prophylactic therapy. PMID- 2208107 TI - Immunological effects of flavone acetic acid. AB - Flavone acetic acid (FAA) enhances natural killer and lymphokine-activated killer (LAK) cell activity in mice. We examined the immunological effects of FAA on human blood cells both in vivo and in vitro. Peripheral blood natural killer and LAK activity and lymphocyte subsets were evaluated in cancer patients after receiving 3-h infusion of FAA at either 8.5 or 10 g/m2 with alkalinization. Natural killer cell activity and the number of Leu-19 (CD56) positive cells decreased at 24 h after infusion; significant changes in LAK activity and the number of Leu-1 (CD5), Leu-3 (CD4), Leu-2 (CD8) cells were not observed. Peripheral blood mononuclear cells and peripheral blood lymphocytes collected from healthy volunteers were exposed in vitro to FAA, interleukin 2, and FAA plus interleukin 2. FAA, alone or in combination, failed to enhance LAK activity at any time point or concentration from peripheral blood mononuclear cells and peripheral blood lymphocytes. Concentrations of greater than or equal to 100 micrograms/ml antagonized the generation of LAK activity from interleukin 2 treated peripheral blood lymphocytes. These data suggest that FAA may not be useful in enhancing immunological responses in humans. PMID- 2208108 TI - Role of carrier ligand in platinum resistance in L1210 cells. AB - We have examined the effect of carrier ligands on platinum accumulation, incorporation of platinum into DNA, cytotoxicity of Pt-DNA adducts, and repair of Pt-DNA adducts in three L1210 cell lines: L1210/0, which is sensitive to most types of platinum compounds; L1210/DDP, which is resistant to platinum compounds with the ethylenediamine (en) carrier ligand but sensitive to those with the diaminocyclohexane (dach) ligand; and L1210/DACH, which is resistant to dach-Pt compounds but sensitive to en-Pt compounds. There was a selective decrease in accumulation of dach-Pt in the L1210/DACH line and of en-Pt in the L1210/DDP line. Intracellular dach-Pt was incorporated into DNA to a lesser extent than en Pt in both resistant cell lines. Cytotoxicity of en-Pt adducts was less than that of dach-Pt adducts in the L1210/DDP line, while the reverse was true in the L1210/DACH line. Increased repair was seen in both resistant cell lines; a carrier ligand effect was seen only in the L1210/DDP line, which showed a greater initial rate of repair for en-Pt than dach-Pt adducts. These data suggest that carrier ligand effects seen in resistant cell lines may be due, in part, to differences in accumulation of platinum, repair of Pt-DNA adducts, and tolerance of Pt-DNA adducts. PMID- 2208110 TI - Substrate-specific deoxycytidine kinase deficiency in 1-beta-D arabinofuranosylcytosine-resistant leukemic cells. AB - In this study we describe the establishment of a leukemic cell line (BNML-CL/ara C), originating from the 1-beta-D-arabinofuranosylcytosine (ara-C)-resistant brown Norway rat myelocytic leukemia model (BNML/ara-C), that retains the in vivo generated ara-C resistance. Its biological and biochemical characteristics have been compared with a cell line, derived from the ara-C-sensitive BNML model (BNML CL/O). Resistance to ara-C was attributed to a decrease in phosphorylation of ara C. Deoxycytidine (dCyd) kinase activity in crude cell extracts with dCyd as substrate showed similar enzyme activities in both cell lines, whereas with ara-C as substrate no dCyd kinase activity was detectable in the ara-C-resistant cell line. Two isoenzymes of dCyd kinase with different substrate specificities have been described (Cheng, Y.C., Domin, B., and Lee, L.S. Biochim. Biophys. Acta, 481: 481-492, 1977), cytoplasmic (dCyd kinase I, substrates: dCyd and ara-C) and mitochondrial (dCyd kinase II, substrates: dCyd and thymidine). In the ara-C sensitive BNML model, thymidine induced a reduction of dCyd kinase activity when dCyd was used as substrate. However, thymidine did not affect kinase activity with ara-C was used as substrate. In the BNML-CL/ara-C, thymidine even induces a dCyd kinase inhibition of 85% with dCyd as substrate. It is likely that the ara-C specific dCyd kinase deficiency in BNML-CL/ara-C cells was due to a selective loss of dCyd kinase I, whereas dCyd kinase II activity remained intact. PMID- 2208109 TI - Smoking and drinking in relation to cancers of the oral cavity, pharynx, larynx, and esophagus in northern Italy. AB - A hospital-based case-control study of upper aerodigestive tract tumors was conducted between June 1986 and June 1989 in Northern Italy. One hundred fifty seven male cases of oral cavity cancer, 134 of pharyngeal cancer, 162 of laryngeal cancer, and 288 of esophageal cancer, and 1272 male inpatients with acute conditions unrelated to tobacco and alcohol were interviewed. Odds ratios for current smokers of cigarettes were 11.1 for oral cavity, 12.9 for pharynx, 4.6 for larynx, and 3.8 for esophagus. For all 4 sites, the risk increased with increasing number of cigarettes and duration of smoking habits and, with the exception of esophageal cancer, decreased with increasing age at the start of and years since quitting smoking. Smokers of pipes and cigars showed a more elevated risk of cancer of the oral cavity and esophagus than did cigarette smokers. Significantly increased risks emerged also in heavy drinkers (odds ratio greater than 60 versus greater than or equal to 19 drinks/week = 3.4, 3.6, 2.1, and 6.0 for oral cavity, pharynx, larynx, and esophagus, respectively), deriving predominantly from wine consumption. PMID- 2208111 TI - Case-control study of residential radon and lung cancer among New Jersey women. AB - To evaluate the association of indoor radon exposure with lung cancer risk, yearlong alpha track detector measurements of radon were conducted in dwellings which had been occupied for at least 10 years by 433 New Jersey female lung cancer cases and 402 controls who were subjects in a larger population-based study. Adjusted odds ratios were 1.1 (90% confidence interval, 0.79-1.7), 1.3 (90% confidence interval, 0.62-2.9), and 4.2 (90% confidence interval, 0.99-17.5) for exposures of 1.0-1.9, 2.0-3.9, and 4.0-11.3 pCi/liter, respectively, relative to exposures of less than 1.0 pCi/liter, showing a significant trend (1-sided P = 0.04) with increasing radon concentration. The trend was strongest among light smokers (less than 15 cigarettes/day, 1-sided P = 0.01). The trend for lung cancer risk with estimated cumulative radon exposure was slightly weaker (1-sided P = 0.09). The increase in relative risk for each unit of cumulative exposure, 3.4% (90% confidence interval 0.0-8.0%) per working level month, was consistent with the range of 0.5-4.0% per working level month generally reported for underground miner studies, supporting the extrapolation of the occupational data to the residential setting. However, the possibility of selection biases, the small number of high exposures, and other uncertainties necessitate caution in interpretation of these data. PMID- 2208112 TI - Plasma pharmacokinetics and cerebrospinal fluid concentrations of idarubicin and idarubicinol in pediatric leukemia patients: a Childrens Cancer Study Group report. AB - Idarubicin (4-demethoxydaunomycin) is an anthracycline analogue with striking in vitro and in vivo activity against murine leukemias. Based on activity in adults with acute lymphoblastic leukemia, the Childrens Cancer Study Group initiated studies to evaluate idarubicin in children with leukemia in second or subsequent relapses. As part of those studies, we have characterized the plasma pharmacokinetics of idarubicin and the major circulating metabolite idarubicinol in 21 patients. Idarubicin plasma elimination was described by a three compartment open model following i.v. infusion (10-15 mg/m2) on a schedule of weekly for 3 weeks and on a schedule of daily for 3 days every 3 weeks (total dose, 30-45 mg/m2). There was substantial variability in idarubicin elimination among patients, but no indication of dose-dependent or of schedule-dependent changes in pharmacokinetic parameters. The mean terminal half-life, total body clearance, and steady state volume of distribution were 17.6 h, 679 ml/min/m2, and 562 l/m2, respectively. Idarubicinol elimination was prolonged compared to that of the parent drug with a terminal half-life of 56.8 h. This metabolite clearly accumulated in plasma during the 3 days of treatment on the schedule of daily for 3 days. Urinary recoveries (48 h) of idarubicin and idarubicinol after a single dose of idarubicin were 2.4 and 10.1%, respectively. Idarubicin was detected in 2 of 21 cerebrospinal fluid samples obtained 18-30 h after administration. In marked contrast, idarubicinol was detected in 20 of those 21 samples. Concentrations in the 20 samples varied from 0.22-1.05 ng/ml with a mean value of 0.51 ng/ml. PMID- 2208113 TI - Cloning of a carcinoembryonic antigen gene family member expressed in leukocytes of chronic myeloid leukemia patients and bone marrow. AB - The carcinoembryonic antigen (CEA) gene family belongs to the immunoglobulin superfamily and can be subdivided into the CEA and pregnancy-specific glycoprotein subgroups. The basic structure of the encoded proteins consists of, in addition to a leader, one IgV-like and 2, 3, or 6 IgC-like domains. These domains are followed by varying COOH-terminal regions responsible for secretion, transmembrane anchoring, or insertion into the membrane by a glycosyl phosphatidylinositol tail. Here we report on the characterization of CGM6, a new member of the CEA gene subgroup, by complementary DNA cloning. The deduced coding region comprises 349 amino acids and consists of a leader, one IgV-like, two IgC like domains, and a hydrophobic region, which is replaced by a glycosyl phosphatidylinositol moiety in the mature protein. CGM6 transcripts were only found thus far in leukocytes of chronic myeloid leukemia patients, in normal bone marrow, and in marginal amounts in normal granulocytes. The CGM6 gene product might, therefore, represent a myeloid marker. Analyses of CGM6 protein-expressing HeLa transfectants with monoclonal antibodies strongly indicate that the CGM6 gene codes for the CEA family member NCA-95. PMID- 2208114 TI - Hydroxyanthraquinones as tumor promoters: enhancement of malignant transformation of C3H mouse fibroblasts and growth stimulation of primary rat hepatocytes. AB - Because danthron, though carcinogenic, does not seem to be genotoxic, it and 8 other hydroxyanthraquinones were comparatively investigated for activities associated with tumor promotion, such as stimulation of cell proliferation and enhancement of malignant transformation. The in vivo treatment of primary rat hepatocytes with danthron, aloe-emodin, chrysophanol, and rhein resulted in a 2-3 fold increase of DNA synthesis, lucidin and purpurin were less active, and emodin, purpuroxanthin, and alizarin were essentially inactive. In addition, danthron, rhein, and chrysophanol (preliminary data), but not alizarin, enhanced transformation of C3H/M2 mouse fibroblasts initiated by N-methyl-N'-nitro-N nitrosoguanidine or 3-methylcholanthrene. The results of these in vitro studies suggest that hydroxyanthraquinones, possessing 2 hydroxy groups in the 1,8 positions, e.g., danthron, rhein, and chrysophanol, may have tumor-promoting activities. This conclusion is in accordance with the hypothesis that the in vivo carcinogenic activity of danthron may be associated with tumor promotion. PMID- 2208115 TI - Increased sensitivity to Vinca alkaloids in cells overexpressing calmodulin by gene transfection. AB - Mouse C127 cells, transfected with the chicken calmodulin (CaM) gene and overexpressing CaM protein, were used to evaluate the effect of elevated levels of CaM on the sensitivity of these cells to various anticancer drugs. Clones C2 and C3 overexpress CaM mRNA by 40- and 80-fold, respectively, and CaM protein 3- and 8-fold, respectively. These cell lines were tested for their sensitivity to vincristine, vinblastine, bleomycin, and Adriamycin by comparing the 50% inhibitory concentration in a 72-h growth inhibition assay. The 50% inhibitory concentration values for vincristine with C2 and C3 cells were 6.27 +/- 0.56 nM and 6.60 +/- 0.96 nM, respectively. These values were significantly lower than 13.9 +/- 0.79 nM for the parental C127 cells and 14.0 +/- 1.55 nM for clone 6.8 (the control cell line for transfection without the chicken CaM gene) at P less than or equal to 0.005. The proliferation of C2 and C3 cells was inhibited at lower concentrations of vinblastine as well. The 50% inhibitory concentration values for the C2 and C3 cell lines were approximately one-half those required for C127 or clone 6.8 cells. However, no significant difference in the sensitivity to the DNA-binding drugs, bleomycin and Adriamycin, was observed between the different cell lines. The uptake of [3H]vinblastine was evaluated and found to be increased 1.6- and 2.8-fold in C2 and C3 cells, respectively, as compared with that value obtained for C127 cells. Moreover, the efflux of [3H]vinblastine from vinblastine-loaded cells was also observed to be decreased in the C2 and C3 cell lines. These data suggest that the increase in CaM expression in the C2 and C3 cell lines might be related to the higher sensitivity of these cells to Vinca alkaloids. This increased sensitivity appears to be due to the increase in intracellular concentration of the Vinca alkaloids as a result of an increase in drug uptake and a decrease in efflux. Moreover, the increased sensitivity of clones C2 and C3 to Vinca alkaloids appears to be specific to this class of drugs in that no collateral effects were observed for the DNA-damaging drugs, Adriamycin and bleomycin. PMID- 2208116 TI - A comparative case-control analysis of stomach cancer and atrophic gastritis. AB - We conducted a comparative case-control analysis of stomach cancer and atrophic gastritis involving 427 cases with stomach cancer, 1414 cases with atrophic gastritis, and 3014 control subjects based on a questionnaire survey conducted for the subjects who received gastroscopic examination at Aichi Cancer Center Hospital from April 1985 to March 1989. The risk of atrophic gastritis in both males and females was not associated with any environmental factors. The risk of stomach cancer compared with the control subjects was positively associated with an intake of salted fish guts or cod roe [relative risk (RR) = 1.52, 95% confidence interval (CI) = 1.08-2.15] and smoking (RR for 20 or more cigarettes per day = 2.84; 95% CI = 1.79-4.51) and inversely associated with Western-style breakfast (RR = 0.68; 95% CI = 0.48-0.96) in males. Additionally, the risk of stomach cancer was inversely associated with a daily intake of raw vegetables (RR = 0.56; 95% CI = 0.34-0.94) in males when compared with the patients with atrophic gastritis as controls. Several environmental factors, such as intake of green-yellow vegetables, fruit, and meat, and a family history of stomach cancer, were only associated with intestinal types of cancer in females, whereas a clear difference between diffuse and intestinal types was not observed in males. The results of the present study suggest that risk factors for stomach cancer may be different from those for premalignant lesions. PMID- 2208117 TI - Antisense-mediated inhibition of BCL2 protooncogene expression and leukemic cell growth and survival: comparisons of phosphodiester and phosphorothioate oligodeoxynucleotides. AB - Antisense oligodeoxynucleotides specific for sequences in mRNAs from the B-cell lymphoma/leukemia-2 (BCL2) gene were used to inhibit the growth in culture of a human leukemia cell line, 697. Normal phosphodiester (PO) and nuclease-resistant phosphorothioate (PS) oligodeoxynucleotides were compared with regard to specificity, potency, and kinetics. Both PO and PS antisense BCL2 oligodeoxynucleotides were specific inhibitors of cellular proliferation, since sense versions of these synthetic DNAs were inactive at similar concentrations. Specificity was further confirmed by quantitative immunofluorescence studies, showing that PO and PS antisense BCL2 oligodeoxynucleotides (when used at appropriate concentrations) reduced levels of BCL2 protein without influencing expression of HLA-DR and other control antigens. The onset of inhibition by PO oligodeoxynucleotides was faster, with reductions in cell numbers occurring within 1 day of addition to cultures, in contrast to phosphorothioates, which were ineffective until 3-4 days. Phosphorothioates were more potent that phosphodiesters, however, with half-maximal inhibition of leukemic cell growth occurring at concentrations 5-10 times lower. As expected from previous studies demonstrating the importance of BCL2 for regulating lymphoid cell survival, BCL2 antisense oligodeoxynucleotides also led to 697 leukemic cell death through sequence-specific mechanisms, with reductions in cellular viability generally lagging the inhibitory effects on cellular growth by about 2 days. Taken together, these data indicate that PO and PS oligodeoxynucleotides targeted against the human BCL2 protooncogene can be sequence-specific inhibitors of leukemic cell growth and survival. PMID- 2208118 TI - Induction and repair of DNA double strand breaks in radiation-resistant cells obtained by transformation of primary rat embryo cells with the oncogenes H-ras and v-myc. AB - Rat embryo cells (REC) transformed by the H-ras oncogene plus the cooperating oncogene v-myc are highly resistant to ionizing radiation as compared with the nontransformed parent cells, REC, or immortalized REC. In an attempt to understand the potential mechanism of resistance in these cells, the induction and repair of double strand breaks (dsb) in DNA were measured in a H-ras plus v myc transformed (3.7) and an immortalized REC (mycREC) line using pulsed field gel electrophoresis. Cells were irradiated in the exponential phase of growth, and the amount of DNA dsb present was quantified by measuring the fraction of DNA activity released from the agarose plugs in which cells were embedded. Similar values of the fraction of DNA activity released were measured for both cell lines at equal X-ray doses, after correction for differences in cell cycle distribution, suggesting a similar induction of DNA dsb per Gy. Repair of DNA dsb measured after exposure to 40 Gy of X-rays was similar in both cell lines and displayed a fast and a slow component. The fast component had a 50% repair time of approximately 12 min, and the slow component, 50% repair time of about 3 h. These results suggest that the relative radioresistance of 3.7 cells is not conferred by a decrease in the amount of DNA dsb induced per Gy per dalton or by alterations in the capacity of the cells to repair DNA dsb. It is hypothesized that alterations in the expression of potentially lethal damage underlie this phenomenon. PMID- 2208119 TI - Combined high-performance liquid chromatography/32P-postlabeling assay of N7 methyldeoxyguanosine. AB - A highly sensitive and specific assay for the detection of N7-methyl-2' deoxyguanosine (N7methyldG) has been developed by combining high-performance liquid chromatography, 32P-postlabeling, and nucleotide chromatography. Separation of normal nucleotides and adducts by high-performance liquid chromatography and then combining a portion of 2'-deoxyguanosine to the N7methyldG allows for quantitation using an internal standard. The directly determined molar ratio is not subject to errors in digestion, variable ATP specific activity, or assumptions in relative adduct-labeling efficiency. The detection limit was one N7methyldG adduct in 10(7) unmodified 2'-deoxyguanosine bases. N7methyldG adducts have been detected in 5 human lung samples in which O6 methyl-2'-deoxyguanosine adducts had been previously determined. The mean ratio of N7methyldG to O6-methyl-2'-deoxyguanosine was determined to be approximately 10. The current assay complements the high-performance liquid chromatography/32P postlabeling assay for O6-methyl-2'-deoxyguanosine and increases the detection sensitivity of DNA methylated by exogenous alkylating agents. PMID- 2208120 TI - Pesticide exposures and other agricultural risk factors for leukemia among men in Iowa and Minnesota. AB - Mortality surveys and death certificate studies have suggested an association between leukemia and farming. To investigate whether exposure to carcinogens in an agricultural setting is related to risk of leukemia, the authors conducted a population-based case-control interview study of 578 white men with leukemia and 1245 controls living in Iowa and Minnesota. Consistent with recent mortality studies, there were slight, but significant, elevations in risk for all leukemia [odds ratio (OR) 1.2] and chronic lymphocytic leukemia (OR 1.4) for farmers compared to nonfarmers. There were no significant associations with leukemia for exposure to specific fungicides, herbicides (including 2,4-D and 2,4,5-T), or crop insecticides. However, significantly elevated risks for leukemia of greater than or equal to 2.0 were seen for exposure to specific animal insecticides including the organophosphates crotoxyphos (OR 11.1), dichlorvos (OR 2.0), and famphur (OR 2.2) and the natural product pyrethrins (OR 3.7) and the chlorinated hydrocarbon methoxychlor (OR 2.2). There were also smaller, but significant, risks associated with exposure to nicotine (OR 1.6) and DDT (OR 1.3). This finding of elevated risks for insecticides used on animals deserves further evaluation. PMID- 2208121 TI - Carcinogenicity of 1,3-butadiene in C57BL/6 x C3H F1 mice at low exposure concentrations. AB - The carcinogenicity of inhaled 1,3-butadiene was evaluated in C57BL/6 x C3H F1 mice exposed to concentrations of this gas ranging from 6.25 to 625 ppm. Butadiene is a high production volume chemical, used mainly in the manufacture of synthetic rubber. In these 2-yr inhalation studies, a potent multisite carcinogenic response was observed, including neoplasms of the lung at concentrations as low as 6.25 ppm. Early occurrence and extensive development of lethal lymphocytic lymphomas in mice exposed to 625 ppm of butadiene reduced the number of animals at risk for the expression of later developing neoplasms at other sites; at lower exposure concentrations, dose responses were demonstrated for hemangiosarcomas of the heart and neoplasms of the lung, forestomach, Harderian gland, preputial gland, liver, mammary gland, and ovary. So far, no long-term studies on butadiene have been conducted at exposure concentrations that have not shown a carcinogenic response. In separate experiments with reduced exposure durations, butadiene induced neoplastic responses at multiple organ sites even after only 13 wk of exposure. Because of the correspondence between these animal data and recent epidemiology findings, there is a worldwide public health need to reevaluate current workplace exposure standards for 1,3-butadiene. PMID- 2208122 TI - Evaluation in vitro of adriamycin immunoconjugates synthesized using an acid sensitive hydrazone linker. AB - A novel method for linking Adriamycin (ADM) to monoclonal antibodies is described in which the 13-keto position of the anthracycline is used as the attachment site to the linker arm. A new ADM acylhydrazone derivative, Adriamycin 13-[3-(2 pyridyldithio)propionyl]hydrazone hydrochloride, which contains a pyridyl protected disulfide, was synthesized and used for conjugation to monoclonal antibodies (MAbs) that were thiolated with N-succinimidyl 3 (pyridyldithiol)propionate or 2-iminothiolane. This resulted in formation of a linker between MAb and drug that contained a disulfide bond. Conjugation conditions were optimized to yield conjugates with high ADM:MAb molar ratios. The final immunoconjugate yields were found to decrease as the ADM:MAb molar ratio of the conjugates increased. Stability studies indicated that ADM was released from the immunoconjugates at mildly acidic pHs ranging from 4.5-6.5. Treatment of immunoconjugates with mild reducing agent dithiothreitol resulted in release of an acylhydrazone derivative of ADM. Flow-cytometric studies showed that the binding activity of various MAbs following conjugation to ADM was preserved at ADM:MAb molar ratios up to 10. Antibody-directed cytotoxicity was demonstrated under several assay conditions using combinations of antigen-positive and antigen negative cells and binding and nonbinding immunoconjugates. In several experiments, ADM immunoconjugates were more potent than equivalent amounts of unconjugated ADM. PMID- 2208123 TI - Antitumor activity of adriamycin (hydrazone-linked) immunoconjugates compared with free adriamycin and specificity of tumor cell killing. AB - Adriamycin (ADM) was chemically coupled to two monoclonal antibodies (MAb) expressed on human B-cell lymphomas. Immunoconjugates were prepared by linking to the MAb an ADM derivative, Adriamycin 13-[3-(2-pyridyldithio)propionyl]hydrazone (ADM-HZN), which releases ADM under mild acidic conditions (see preceding article). The (ADM-HZN) conjugates were tested for antitumor activity on two human B-lymphoma xenografts, Daudi and Ramos, which were growing as solid tumors in athymic mice. The conjugates, injected i.p., significantly inhibited tumor growth when antibody protein doses were greater than or equal to 500 mg/kg (approximately 10 mg/mouse). At these input antibody doses, (ADM-HZN) conjugates were more potent and had greater antitumor activity than free ADM given at an optimized dose and schedule. MAb-conjugated ADM was also tolerated to much higher levels than unconjugated drug. Antitumor activity was not obtained using mixtures of MAb plus free drug or with MAb-drug conjugates that did not bind to the tumor target cell. Thus, the antitumor activity of the immunoconjugate was directed by binding of the MAb portion of the conjugate to target tumor cells. PMID- 2208124 TI - Clonotypic heterogeneity in cutaneous T-cell lymphomas. AB - The antigen receptor genes studied (immunoglobulin gene for B-cells, and T-cell receptor -beta or -gamma gene for T-cells) represent the most powerful tools for diagnosing the clonality of a lymphoid lineage. We have clonotyped 23 cutaneous T cell lymphomas and 5 were found to be clonotypically all heterogeneous. Analysis of each patient was performed either from serial skin biopsies taken several months apart or from different tumor samples. In these cases, T-cell lymphoma clonotypic heterogeneity was demonstrated and was especially evident when examining different tumor sites. Moreover, in one case, a biogenotypic population (immunoglobulin and T-cell receptor-rearranged) was found. This unexpected high frequency of T-cell clonal heterogeneity (22%) could be explained either by the evolution of subclones from a single undifferentiated malignant cell or by the independent transformation to cancer of 2 or more lymphocytes, though the latter seems less likely. Clonotypic heterogeneity seems to be as frequent in T-cell lymphomas with cutaneous lesions as in B-cell leukemias. PMID- 2208125 TI - Mechanisms of resistance of confluent human and rat colon cancer cells to anthracyclines: alteration of drug passive diffusion. AB - Two colon cancer cell lines, HT-29 (human) and DHD/K12/TRb (rat), were grown as monolayer cultures to various confluence degrees. The cytotoxic efficacies of doxorubicin and 4'-deoxydoxorubicin, evaluated by a survival assay, and the nuclear drug concentrations, measured by microspectrofluorometry, were shown to progressively decrease with the augmentation of confluence. This confluence dependent resistance (CDR) to anthracyclines was demonstrated independent of the multidrug resistance drug efflux mechanism. The cellular uptake of three compounds (sodium [51Cr]chromate, D-[14C]alanine, L-[14C]glucose) known to passively diffuse across the cell membrane as anthracyclines do was also reduced in confluent cells. After trypsin cell detachment, the kinetics of reversion of the sodium [51Cr]chromate uptake decrease and that of CDR were similar. Therefore, CDR may be attributed to a reduction of anthracycline cell intake due to a general alteration of passive diffusion across the cell membrane. However, CDR is only partly explained by this phenomenon since a reduced sensitivity of confluent cells was observed compared with nonconfluent cells for a similar amount of drug in their nuclei. CDR could explain the high resistance to anthracyclines of some solid tumors, such as colon tumors, in which cancer cells are tightly aggregated. PMID- 2208126 TI - Estrogen and progesterone receptors in bronchogenic carcinoma. AB - Although the lung is not usually considered a major target organ of sex hormones, epidemiological observations, studies of pulmonary neoplasms in laboratory animals, and investigations of carcinomas derived from other "nontarget" organs suggest that sex hormones may have a role in the pathogenesis of bronchogenic carcinoma. To confirm that estrogen (ER) and progesterone receptors are present in human lung cancers, 19 resected lung cancers were examined for receptors using a prelabeled sucrose gradient method. Three squamous cell carcinomas were positive for ER (greater than 6.9 fmol/mg cytosol protein). Three squamous cell carcinomas, two adenocarcinomas, and one small cell carcinoma were positive for progesterone receptors (greater than 6.9 fmol/mg cytosol protein). One tumor, a squamous cell carcinoma arising in a woman who smoked, had an ER level of 301 fmol/mg, a highly positive level even for breast cancers. These observations may provide a basis for adjuvant hormonal therapy in selected lung cancer patients. PMID- 2208127 TI - Acetylation phenotype is not associated with breast cancer. AB - In the present study, we have measured acetylation phenotype in 45 patients who had undergone surgical resection of a primary adenocarcinoma of the breast and in 48 patients or volunteer subjects with no breast disease. Phenotype was determined by measuring the ratio of N-acetylsulfamethazine to N acetylsulfamethazine plus sulfamethazine in plasma 6 h after a p.o. dose of sulfamethazine. In the control group, there were 31 slow and 17 rapid acetylators, while in the breast patients, there were 25 slow and 20 rapid acetylators. The proportions of slow/rapid acetylators were not significantly different between the 2 groups (Pearson's chi 2 with Yates' correction = 0.45; P = 0.51). The data suggest that acetylation phenotype is not a useful risk prediction measurement in breast cancer. PMID- 2208128 TI - Effects of leucovorin on idoxuridine cytotoxicity and DNA incorporation. AB - Leucovorin (LV) increased the growth inhibition produced by iododeoxyuridine (IdUrd), a halogenated analogue of thymidine, in a murine tumor cell line (L1210) and three human tumor cell lines (HL-60, HT-29, and MCF-7). This increased growth inhibition was associated with increased incorporation of IdUrd into DNA. Consistent with previous reports, IdUrd (as iododeoxyuridine monophosphate) inhibited thymidylate synthase (TS) and was dehalogenated intracellularly by TS to generate thymidine nucleotides. In all four cell lines, LV decreased the dehalogenation of IdUrd, producing a 3-fold increase in the labeled iododeoxyuridine triphosphate/dTTP ratios in cytoplasm and labeled IdUrd/thymidine in DNA derived from tritiated IdUrd. In intact L1210 cells, apparent TS activity was inhibited 50% by 3 microM IdUrd alone and 75% by the combination of 3 microM IdUrd and 20 microM LV. Apparent TS activity was unchanged with 20 microM LV alone. In all cell lines except HL-60, the ratios of labeled iododeoxyuridine triphosphate/dTTP derived from tritiated IdUrd were 3 fold lower than the labeled IdUrd/thymidine ratios in DNA. This observation suggests that replicative DNA polymerases preferentially incorporate iododeoxyuridine triphosphate into DNA compared to the endogenous substrate dTTP. This preferential incorporation was independent of the effect of LV. These novel findings suggested that a potential mechanism for the effects of LV on IdUrd was increased inhibition of TS analogous to the interaction between fluoropyrimidines and LV. Enzyme inhibition studies using L1210 cell extracts showed that iododeoxyuridine monophosphate was a weak inhibitor of TS (Ki greater than 10 microM) when compared to 5-fluorodeoxyuridine monophosphate (Ki less than 10 nM). Despite the major differences in potency of these two halogenated pyrimidines, LV appears to modulate the activity of IdUrd as well as 5-fluorodeoxyuridine. LV may provide a clinically useful approach to improve the radiosensitizing and/or cytotoxic properties of IdUrd. PMID- 2208129 TI - Expression of a Mr 41,000 glycoprotein associated with thrombin-independent platelet aggregation in high metastatic variants of murine B16 melanoma. AB - In the previous study, we generated a monoclonal antibody, 8F11, against NL-17, a high metastatic clone derived from a metastatic variant of murine colon adenocarcinoma 26. 8F11 inhibited platelet aggregation induced by NL-17 and recognized a Mr 44,000 membrane protein as antigen. In the present study, the reactivity of 8F11 to murine B16 melanoma and its metastatic variants was examined, and the antigen recognized by 8F11 on the cell surface was characterized. 8F11 was found to strongly react with 3 metastatic variants of B16 melanoma. In contrast, only slight reactivity was observed with parent B16 melanoma. The reactivity of the antibody to these cells was in the order B16F10 greater than B16BL-6 greater than B16F1 much greater than B16. Western blot analysis showed a Mr 41,000 protein as the antigen recognized by 8F11 on the cell surface of B16F10 cells. The Mr 41,000 antigen appeared to be a glycoprotein that bound to wheat germ agglutinin as has been observed for the Mr 44,000 antigen of NL-17. To elucidate the functional role of the Mr 41,000 antigen in B16 melanoma, platelet aggregation induced by B16 and B16F10 was compared. B16 was reported to stimulate platelet aggregation by the generation of thrombin, whereas B16F10 was found to activate platelet by at least 2 mechanisms: one dependent on thrombin and the other independent on thrombin. The activity of B16 and its metastatic variants to induce platelet aggregation in the presence of MD805, a synthetic antagonist of thrombin, well correlated with the reactivity of 8F11 to these cells. 8F11 blocked platelet activation by B16F10 under conditions preventing thrombin activity such as enzymatic formation of lysolecithin through the treatment of the cell surface with phospholipase A2 or in the presence of MD805. These data indicate that Mr 41,000 glycoprotein recognized by 8F11 on metastatic variants of B16 melanoma is involved in the thrombin-independent platelet aggregation. A positive correlation was observed between the levels of Mr 41,000 glycoprotein expression of B16 and its metastatic variants and their pulmonary metastasis after i.v. injection, suggesting Mr 41,000 glycoprotein, as well as other factors reported previously, may play an important role in the hematogenous spread of B16 melanoma. PMID- 2208130 TI - Quantitative measurements of the changes in protein thiols in cervical intraepithelial neoplasia and in carcinoma of the human uterine cervix provide evidence for the existence of a biochemical field effect. AB - Quantitative micromethods have been used for measuring reactive protein thiols (PSHr), total reactive protein sulfur (TRPS), total protein thiols (PSHt), and protein disulfides (PDS) in fixed frozen sections of human uterine cervix. PSHr and TRPS were stained using 2,2'-dihydroxy-6,6'-dinaphthyl disulfide; PSHt and PDS were stained using mercurochrome methods. Microspectrophotometric measurements were made on the stained sections using a microdensitometer with associated data processing; the results obtained for areas of epithelium and stroma were converted to absorbance values per micron 2. Samples of uterine cervix that were diagnosed as containing cervical intraepithelial neoplasia (CIN) I-III or carcinoma were examined and compared with samples of normal uterine cervix. Measurements were made not only on identified lesions but also on apparently normal tissue obtained from the same cervix. Epithelial/stroma ratios (E/S) were calculated for PSHr, TRPS, PSHt and PSHt + PDS; in addition, the double ratios of PSHr/TRPS and PSHt/PSHt + PDS were also calculated for E/S. The mean E/S values for PSHr and PSHt were significantly different for all types of lesion compared with control samples. The E/S ratios for apparently normal tissue obtained from cervices with CIN or carcinoma were also significantly different compared with corresponding control values, indicating a field effect. There was a considerable degree of overlap between individual values in the control groups versus those obtained with each type of lesion. The corresponding mean E/S values for TRPS and for PSHt + PDS in the samples containing lesions were not significantly different from control means except for the group containing CaCx. However, the mean values for the double ratios (PSHr/TRPS and PSHt/PSHt + PDS) were significantly different in the groups containing lesions compared with the controls. Moreover, apparently normal tissue obtained from cervices containing CIN or carcinoma had different mean values compared with the controls, confirming the existence of a field effect. The degree of overlap of individual values in the lesion groups compared with the control values was much less with double ratio values than previously noted for single ratio values. In consequence, the double ratio measurements clearly discriminated CIN I + II and CIN-III from controls. Our data show that CIN is associated with marked changes in tissue protein thiols and disulfides and that these differences extend to neighboring apparently normal tissue indicative of a field effect. PMID- 2208131 TI - Characterization of an N-methyl-N-nitrosourea-induced autochthonous rat bladder cancer model. AB - Cohorts of 4- to 5-wk-old female Fischer 344 rats received four biweekly 1.5-mg doses of N-methyl-N-nitrosourea (MNU) intravesically and were sacrificed at various intervals. By 13 wk after initiation of the carcinogen, all animals have flat epithelial atypia and/or papillary transitional cell bladder carcinomas, and 67% of the lesions are histological Grade II or III. By 20 wk, 83% have gross bladder wall muscle-invasive tumors that eventually kill the host. There was no gross evidence of visceral metastases in any animal. This rat model of transitional cell carcinoma of the bladder is useful because: (a) all animals develop progressive neoplastic changes in situ within 4 mo after initiation of MNU treatment; (b) these lesions progress to grossly detectable bladder tumors which invade the bladder wall and kill the host; (c) this full progression of bladder epithelial cells from atypical hyperplasia through flat carcinoma in situ to transitional cell carcinoma occurs at discrete time points; (d) the histology of the grossly detectable tumors is that of invasive transitional cell carcinomas; and (e) no leukemias, breast cancers, lymphomas, or other non-bladder tumors are induced. Six MNU-induced bladder wall-invasive tumors were karyotyped, and all tumors were diploid with 42 chromosomes. Three of the tumors had apparently normal karyotypes, while three tumors had karyotypes containing one or more cytogenetic structural markers. One of these markers (i.e., 8p+) was observed in two of the three tumors. The level of expression of total ras p21 (N , Ki-, and Ha-ras p21) and codon 12-mutated c-Ha-ras p21 (i.e., glycine to glutamic acid mutation in codon 12) in a series of these MNU-induced bladder tumors was determined by Western blot analysis. No increase in the total ras p21 nor any expression of codon 12-mutated c-Ha-ras p21 was detected in any of these tumors. PMID- 2208132 TI - Mitochondrial DNA modulation of the anchorage-independent phenotype of transformed avian cells. AB - The progressive loss of mitochondrial DNA in the presence of ethidium bromide in immortal avian cell lines correlates with a decrease in their potential for anchorage-independent growth in soft agar. In short-term treated cells, this effect is reversible and the recovery of cloning potential parallels the recovery of control levels of mitochondrial DNA. Long-term ethidium-bromide-treated cells are permanently respiration-deficient and display anchorage-dependent growth. Anchorage-independent revertants can be selected, suggesting that the lack of a respiratory chain per se might not be responsible for the inability of mitochondrial DNA-depleted cells to grow in soft agar. Cybrids formed from the fusion of mitochondrial DNA-depleted, anchorage-dependent cells to cytoplasts from parental cells are capable of growth in soft agar. The mitochondria-specific inhibitor, rhodamine 6G, prevents the recovery of the anchorage-independent phenotype in similar hybrids. These results suggest that mitochondrial DNA is required to maintain the transformed phenotype of avian cells. PMID- 2208133 TI - Human glioblastoma cells release interleukin 6 in vivo and in vitro. AB - This study demonstrates interleukin 6 (IL-6) production and release by human glioblastomas. Twenty glioblastoma cell lines were tested for IL-6 bioactivity using an IL-6-dependent cell line (7TD1). All of the lines tested with one exception (LN-229) constitutively released IL-6. A significant induction of IL-6 production and secretion was observed when LN-229 cells were treated with interleukin 1 beta (IL-1 beta) or tumor necrosis factor alpha. Various amounts of IL-6 mRNA were found in five of six cell lines tested. IL-6 mRNA was detected in line LN-229 only when the cells were treated with IL-1 beta or tumor necrosis factor alpha, confirming the bioassay data. Glioblastoma cells also produce IL-6 in vivo. (a) IL-6 activity was detected in 11 of 13 cerebrospinal fluids and five of five tumor cyst fluids. (b) IL-6 mRNA was found in four of four tumors. (c) Immunohistochemical analysis showed IL-6 within the tumor cells in 15 of 20 glioblastoma sections. In conclusion, biologically active IL-6 is released by almost all glioblastomas both in vitro and in vivo. The elevated levels of serum acute phase proteins and immune complexes found in glioblastoma patients may be the result of this secretion. PMID- 2208134 TI - Insulin-like growth factor gene expression in human smooth muscle tumors. AB - A role for insulin-like growth factors (IGF) in autocrine or paracrine growth stimulation of tumor cells has been proposed for tumors of different origins. We have studied IGF gene expression in human uterus smooth muscle (myometrium) and in a panel of benign (leiomyoma) and malignant (leiomyosarcoma) smooth muscle tumors. Using RNA transfer blot analysis we could demonstrate that in smooth muscle tissue and tumors IGF genes are differentially expressed. The mRNA species detected had the same size as reported for IGF mRNAs from other tissues. However, the abundance of the IGF gene transcripts varied from tissue to tissue. The amounts of IGF mRNAs detected in smooth muscle tumors were compared to the levels found in normal smooth muscle. The IGF-I gene was expressed at high levels in normal myometrium and in leiomyomas but appears to be repressed in leiomyosarcomas. Also the IGF-I peptide was detected in myometrium and in leiomyomas, but in leiomyosarcomas the level was substantially lower. The IGF-II gene was expressed at low levels in normal myometrium and leiomyomas but is activated in leiomyosarcomas. With increasing malignancy from the two major IGF II mRNA species, 6.0 and 4.8 kilobases, in particular the 6.0-kilobase mRNA is produced at higher levels. In conclusion, these data suggest that for IGF-I a role in tumor cell growth is not likely, but probably IGF-II is involved in malignant smooth muscle tumor growth progression. PMID- 2208135 TI - Potent cytotoxicity of an antihuman transferrin receptor-ricin A-chain immunotoxin on human glioma cells in vitro. AB - The cytotoxic effects of an antihuman transferrin receptor monoclonal antibody ricin A-chain conjugate (anti-TfR-A) immunotoxin on glioma cells were assessed in vitro. Five human glioma cell lines were studied; three were derived from surgical explants (MG-1, MG-2, MG-3) and two were well characterized established glioma cells (U-87 MG, U-373 MG). The C6 rat glioma line served as a nonhuman control. One of six lines (U-373) expressed glial fibrillary acidic protein, as assessed by immunohistochemistry. All five human lines expressed human transferrin receptor, as assessed by flow cytometry; no human transferrin receptor was demonstrable on rat C6 cells. Potent inhibition of protein synthesis was found after an 18-h incubation with anti-TfR-A. Fifty % inhibitory concentration (IC50) values for human glioma cells ranged from 1.9 X 10(-9) to 1.8 X 10(-8) M. In contrast, no significant inhibition of leucine incorporation was observed when anti-TfR-A was tested on rat cells (IC50 greater than 10(-7) M) or when a control immunotoxin directed against carcinoembryonic antigen was substituted for anti-TfR-A on human glioma cells (IC50 greater than 10(-7) M). Coincubation with the carboxylic ionophore monensin (10(-7) M) decreased the IC50 of anti-TfR-A against human glioma lines from 16- to 842-fold (range, 7.0 X 10( 12) to 1.5 X 10(-10) M). In contrast, an IC50 of greater than 10(-7) M was obtained when C6 cells were incubated with anti-TfR-A and monensin. Anti-TfR-A immunotoxins potentiated by monensin are extremely potent in vitro cytotoxins for human glioma cells. PMID- 2208136 TI - Increased erbB-2 gene copies and expression in multiple stages of breast cancer. AB - In order to examine the role of the erbB-2 oncogene in human breast cancer, gene amplification and expression were examined in multiple stages of tumor progression. Gene amplification ranging from 2-fold to 32-fold was found in 30 (29%) of 130 cases analyzed. Expression of the receptor-like gene product was determined by a combination of Western immunoblotting and immunohistochemistry. In each case of gene amplification, there was high level overexpression (+ + +) of the protein product. In an additional 29 of 111 cases in which expression was studied (26%), there was moderate level overexpression (+ +) of erbB-2 in the absence of gene amplification. Amplification and overexpression of the erbB-2 gene were found in early clinical stages of breast cancer as well as in more advanced cases. In 23 patients, gene number and level of gene expression were equivalent in the primary tumor site compared with single or multiple metastatic sites in regional lymph nodes. Using a combination of immunohistochemistry and in situ cytohybridization, high (+ + +) and moderate (+ +) level overexpression were homogeneously present in all malignant epithelial cells within histological sections of both primary and metastatic tumor. The intraductal component of carcinoma was identified in sections from 16 invasive primary tumors. erbB-2 gene expression in the intraductal lesions was equivalent to or exceeded expression in the infiltrating components of these tumors. Because erbB-2 alterations are (a) present in all clinical stages, (b) maintained during metastatic spread, (c) homogeneously present throughout tumor sections, and (d) present in the in situ as well as infiltrating component, we conclude that these alterations are selected for early and may be important in the initiation of certain mammary cancer. PMID- 2208137 TI - Subcutaneous recombinant interleukin 2 in a dose escalating regimen in patients with metastatic renal cell adenocarcinoma. AB - Recombinant human interleukin 2 (rIL-2) was administered by s.c. injection daily, 5 days/week to patients with metastatic renal cell carcinoma in an escalating dose regimen. Fifteen patients were entered in this study and are evaluable for toxicity with one patient not evaluable for response because of lack of measurable disease. The patient population had a median age of 63 years with initial performance status (Southwest Oncology Group criteria) of 0 in one patient, 1 in eight patients, and 2 in six patients. The starting dose was 5 x 10(5) Cetus units/m2/day with dose escalation to 1 x 10(6), 2 x 10(6), 4 x 10(6), and 5 x 10(6) Cetus units/m2/day scheduled at 2-week intervals if no significant toxicity or response was noted. Six patients were treated with drug doses of 2 x 10(6) Cetus units/m2/day or higher with a maximum daily dose achieved of 2 x 10(6) units/m2 in two patients, 4 x 10(6) units/m2 in two patients, and 5 x 10(6) units/m2 in two patients. Fatigue with decrease in performance status and elevations in serum creatinine were the most common reasons for limiting the dose or removing a patient from the study. Only one minor anti-tumor response was seen. Subcutaneously administered rIL-2 was able to alter immunological parameters. In two of the three patients tested, development of lymphokine activated killer cell activity in vivo was seen, and statistically significant enhancement of natural killer cell activity compared to values from a concurrently run normal control was demonstrated. With treatment, there was a trend toward increased numbers of circulating total lymphocytes, OKT 8+, OKT 11+, Leu 7+, and Leu 11a+ cells and decreased numbers of circulating OKT 3+ and OKT 4+ cells. However, for the heterogeneous group of six patients monitored, results were not statistically significant compared to pretreatment values. The levels of rIL-2-specific antibodies were followed in the sera of 10 patients. Six of the 10 developed rIL-2-specific IgG during treatment with five of the six patients also developing neutralizing activity. Recombinant human interleukin 2 given by the s.c. route in the doses and schedule used in this trial can safely be given as an outpatient regimen with manageable toxicity. It may result in enhanced immune function in some patients but also results in a high incidence of antibody formation. PMID- 2208138 TI - Cytological study of vacuolated cells and other aberrant hepatocytes in winter flounder from Boston Harbor. AB - A light and electron microscopic study of hepatocytes in winter flounder (Pseudopleuronectes americanus) from Boston Harbor has revealed 3 types of abnormal parenchymal cells in the livers of these fish. (a) Electron-lucent or "light" appearing hepatocytes had the following cytological features indicative of necrosis and cell death: an overall edematous (hydropic) appearance; swollen nuclei with marginated chromatin; moderately swollen, dense mitochondria with flocculent densities; fragmented profiles of endoplasmic reticulum membranes; and lysosome-like bodies. (b) Electron-dense or "dark"-appearing hepatocytes were shrunken and irregular in shape, had a highly condensed cytoplasm, and had dense nuclei that frequently contained vacuoles. In addition, variably sized, organelle containing fragments of these cells were infrequently observed in adjacent "light" hepatocytes or histiocytes possibly resulting from apoptosis. (c) Vacuolated hepatocytes arranged in ductular or acinar configurations demonstrated signs of chronic cell injury such as numerous autophagic vacuoles, condensed mitochondria, and a modified endoplasmic reticulum system, the dilated cisternae of which appeared to form the large vacuole of the cell. While experimental verification is lacking, it is presumed that the various hepatocyte alterations observed in these fish were induced by environmental hepatotoxins. PMID- 2208139 TI - Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression. AB - Since tumor progression is dependent on the ability of malignant cells to interact with the extracellular matrix, molecules on the cell surface which mediate cell-substratum interactions are likely to be important regulators of tumor invasion and metastasis. The purpose of this study was to examine the distribution of one such group of cell adhesion receptors, the integrins, in benign and malignant lesions of human melanocytes. The distribution of integrin adhesion receptors was defined on cells in culture derived from normal and malignant melanocytes and in tissue sections from benign to increasingly malignant melanocytic lesions using a panel of monoclonal antibodies against specific integrin subunits. Cells in culture expressed a large variety of integrins, including all of the previously characterized members of the beta 1 subfamily plus the alpha v/beta 3 vitronectin receptor. The expression of integrins was similar in cells cultured from either benign or malignant lesions. In contrast, consistent differences were noted in integrin expression by cells within tissues containing metastatic and vertical growth phase melanomas when compared to radial growth phase melanoma cells and cells within nevi. Most notably, the expression of the beta 3 subunit was restricted exclusively to cells within vertical growth phase and metastatic melanomas. The presence of this integrin may be important in the development of tumor invasiveness and could be useful as a marker of melanoma cells entering the more aggressive phase of the malignant process. PMID- 2208140 TI - The cell cycle: myths and realities. PMID- 2208141 TI - Specific binding and growth effects of bombesin-related peptides on mouse colon cancer cells in vitro. AB - In the present study, we characterized specific binding of bombesin (BBS)/gastrin releasing peptide (GRP) to mouse colon cancer (MC-26) cells. MC-26 cells were inoculated into male BALB/c mice subdermally, and tumors were harvested from mice 21-28 days postinoculation. Tumor membranes were analyzed for binding to GRP related peptides, using either 125I-GRP or 125I-tyrosine4-BBS. Under optimal binding assay conditions, BBS displaced specific binding of both 125I-GRP and 125I-tyrosine4-BBS in a dose-dependent manner, and a curvilinear displacement resulted. Specific binding data, analyzed by either a Scatchard or a Lineweaver Burk plot, demonstrated presence of 2 classes of specific binding sites, arbitrarily named type I and type II sites. Type I sites had a high binding affinity [Kd 0.45 +/- 0.05 nM (SE)] and a relatively low capacity (226 +/- 27 fmol/mg membrane protein), whereas type II sites had a 10-20-fold lower binding affinity and approximately 6-7-fold higher capacity. BBS/GRP binding sites were specific for GRP-related peptides and demonstrated no significant binding affinity for all other unrelated peptides tested. Relative binding affinity of GRP analogues was in the order of GRP (14-27) greater than neuromedin C greater than or equal to BBS greater than or equal to GRP (1-27) greater than neuromedin B (for the later, P greater than 0.05 versus other peptides). Two BBS receptor antagonists, [D-Arg1,D-trp7,9,Leu11]-substance P (spantide) and [Leu13-psi (CH2NH)Leu14]BBS also inhibited specific binding of 125I-GRP in a dose-dependent manner. Molecular weight of GRP/BBS binding proteins on tumor membranes was determined by cross-linking methods. A major molecular form (greater than 80-90%) (Mr approximately 75,000) and a minor Mr approximately 180,000 band were evident, both under reducing and nonreducing conditions. BBS (0.5-50 nM) demonstrated a significant dose-dependent growth effect on MC-26 cells in vitro, in terms of [3H]thymidine and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide uptake; these studies indicate that the BBS/GRP binding sites on MC-26 cells may serve as functional receptors and mediate the growth effects of BBS on MC-26 cells. PMID- 2208142 TI - Ovariectomy accelerates the growth of microscopic hepatocellular neoplasms in the mouse: possible association with whole body growth and fat deposition. AB - Ovariectomy (ovex) shortens the latency for development of hepatocellular neoplasms in mice, but the mechanism by which this occurs is not known. In the present study, B6C3F1 mice were given single i.p. injections of diethylnitrosamine (5 mg/kg) when they were 15 days old and either ovexed or sham operated 7 weeks later. Groups of 6 to 8 mice were killed after an additional 8, 14, 20, and 26 weeks. Four ovexed and four sham-operated mice were also killed after 56 weeks. By 8 weeks after surgery, the fractional volume of microscopic liver neoplasms in the ovexed mice was 4.3 times greater than in the shams and ablation had caused a 27% greater gain in body weight. During the following 18 weeks, tumor burdens were 3.9 to 10.6 times greater in ovexed than in the sham operated mice and the rates of weight gain were similar in the two groups. Stereological analysis indicated that ovexed animals had more tumors than sham operated animals, 575 versus 234/liver at 8 weeks and 952 versus 724/liver at 14 weeks after surgery. The ovex-induced increase in the number of neoplasms was spread throughout most of the size classes at both times; however, the impact on tumor burden of a small number of large tumors was only apparent at 14 weeks, when 8% of them accounted for more than two thirds of the aggregate tumor volume. The effect of the early emergence of these more rapidly growing tumors was also obvious at 1 year, when the livers of ovexed mice were more than twice the size of the shams (5.1 versus 1.8 g) and they contained 4 times as many tumors larger than 1 cm in diameter than the shams (2 versus 0.5/mouse). Since these very large tumors were invariably, at least partially, composed of trabecular hepatocellular carcinoma, ovariectomy appears to have also fostered tumor progression. The time course of ovex-stimulated weight gain and the manner in which it affected body composition were also analyzed. Eight days following ovex, the rate of weight gain abruptly increased. The acceleration persisted for only 14 days, after which it leveled off at body weights that were 24% higher than in sham-operated mice. The difference in weights resulted from 2.5 times more fat and 10% more protein in the carcasses of ovexed than sham-operated mice. This study identifies an early 8-week period in which hormonal changes resulting from ovex maximally stimulate the growth of liver tumors.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2208144 TI - Sialomucin and lytic susceptibility of rat mammary tumor ascites cells. AB - The potential role of cell surface sialomucin in preventing natural killer (NK) mediated lysis of tumor cell targets has been addressed by comparing the properties of 2 NK-resistant [ascites (ASC) and short-term cultured (STC)] and 2 NK-susceptible [tunicamycin-treated (TUN) and long-term cultured (LTC)] preparations of 13762 MAT-B1 rat mammary tumor cells. Both the ASC and STC cell preparations contain elevated levels of the sialomucin ASGP-1 relative to TUN and LTC preparations as determined by [3H]glucosamine labeling and by binding of peanut agglutinin. The major difference in the susceptibility to NK-mediated lysis appeared to be due to the differences in the susceptibility to lysis by lytic granules, rather than to differences in the ability to bind or trigger effector cells, since TUN and LTC cells were approximately 10-fold more sensitive to lysis by lytic granules than were ASC and STC cells. All preparations inhibited the lysis of the susceptible target YAC-1 by normal rat splenocytes, indicating an ability to bind these effector cells. Triggering of effectors, as monitored either by incorporation of 32P into phosphatidylinositol or by transmethylation of phosphatidylcholine, was similar for the positive control YAC 1, STC, TUN, and LTC, whereas ASC appeared to be defective in triggering effectors. These results suggest that tumor sialomucin blocks the final phase of lysis, but not the initial recognition of tumor cells by NK effectors. PMID- 2208143 TI - Clonal analysis of human meningiomas and schwannomas. AB - Meningiomas and schwannomas are two of the most common tumors of the human nervous system. To determine whether these tumors arise from a single cell or from multiple cells, we used molecular genetic techniques to study X chromosome inactivation in meningiomas and schwannomas isolated from females including one who had neurofibromatosis type 2. The tumors were also screened for loss of heterozygosity at several loci on chromosome 22 using polymorphic DNA markers. Among nine meningiomas, at least three of which showed loss of alleles on chromosome 22 and five of which retained heterozygosity for the chromosome 22 alleles examined, all nine tumors were monoclonal. Among eight schwannomas, at least seven of which retained heterozygosity for chromosome 22 loci, seven were monoclonal. We conclude that human meningiomas and schwannomas arise from a single cell. PMID- 2208145 TI - Protective effects of voluntary exercise during the postinitiation phase of pancreatic carcinogenesis in the rat. AB - Studies were undertaken to evaluate the effects of exercise on the development of pancreatic cancer. Exercise is one life-style factor that has received little attention with regard to its role in the etiology of cancer. Male Lewis and female F344 rats were initiated with azaserine during the suckling period and weaned to the experimental protocols. Food and water were available ad libitum. A purified diet of 20% unsaturated fat was fed to both the sedentary and exercise groups. Rats of the exercise group had free access to voluntary exercise wheels. At approximately 2 and 4 months postinitiation, pancreases were evaluated for the number and size of azaserine-induced putative preneoplastic foci by quantitative stereology. Voluntary exercise activity peaked at approximately 2 months postinitiation with a gradual decline in activity there-after. Male Lewis rats averaged 0.95 +/- 0.13 km/day (SE) and female F344 rats averaged 2.73 +/- 0.26 km/day of voluntary wheel running. Compared with the sedentary groups, male Lewis and female F344 rats with access to the running wheels had significantly smaller foci at 4 months postinitiation. Azaserine-induced foci were evaluated in the male Lewis rats at both 2 and 4 months postinitiation. At 4 months postinitiation, the size and growth rate (as measured by [3H]thymidine autoradiography) of foci were less in the rats with access to the exercise wheels. No differences were observed at 2 months postinitiation. Access to voluntary exercise reduced the growth rate of azaserine-induced pancreatic foci. The effect occurred late in the postinitiation phase and was not directly related to the extent of running activity early in the postinitiation phase. PMID- 2208146 TI - Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in mouse lung microsomes and its inhibition by isothiocyanates. AB - The tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) induces lung tumors in rats, mice, and hamsters, and metabolic activation is required for the carcinogenicity. 2-Phenethyl isothiocyanate (PEITC), whose precursor gluconasturtiin (a glucosinolate) occurs in cruciferous vegetables, has been found to inhibit carcinogenesis by NNK. The purpose of the study was to investigate the enzymes involved in the metabolism of NNK in lung microsomes and to elucidate the mechanisms of inhibition of NNK metabolism by isothiocyanates. NNK metabolism in lung microsomes (isolated from female A/J mice) resulted in the formation of formaldehyde, 4-hydroxy-1-(3-pyridyl)-1-butanone (keto alcohol), 4 oxo-4-(3-pyridyl)butyric acid (keto acid), 4-(methylnitrosamino)-1-(3-pyridyl-N oxide)-1-butanone, and 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanol, displaying apparent Km values of 5.6, 5.6, 9.2, 4.7, and 2540 microM, respectively. Higher Km values in the formation of formaldehyde and keto alcohol were also observed. When cytochrome P-450 inhibitors [2-(diethylamino)ethyl 2,2-diphenylpentenoate] hydrochloride (100 microM), carbon monoxide (90%), and 9-hydroxyellipticine (10 microM) were used, NNK metabolism was inhibited by each 70, 100, and 30%, respectively. Methimazole (1 mM), an inhibitor of the flavin-dependent monooxygenase, inhibited the formation of 4-(methyl-nitrosamino)-1-(3-pyridyl-N oxide)-1-butanone and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol by 20%, but had no effect on the formation of keto alcohol. Inhibitory antibodies against cytochromes P-450IIB1 and -2, P-450IA1, and P-450IA2 inhibited the formation of keto alcohol by 25, 15, and 0%, respectively. Administration of PEITC at doses of 5 and 25 mumol/mouse 2 h before sacrifice produced a 40 and 70% decrease in microsomal NNK metabolism, respectively. PEITC and 3-phenylpropyl isothiocyanate exhibited a mixed type of inhibition, and the competitive component of inhibition had apparent Ki values of 90 and 30 nM, respectively. Preincubation of PEITC in the presence of a NADPH-generating system did not result in a further decrease in the formation of NNK metabolites, indicating that the metabolism of PEITC was not required for the inhibition. When a series of isothiocyanates with varying alkyl chain length (phenyl isothiocyanate, benzyl isothiocyanate, PEITC, 3-phenylpropyl isothiocyanate, and 4-phenylbutyl isothiocyanate) were used, the potency of the inhibition increased with the increase in chain length.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2208147 TI - Pharmacologically directed design of the dose rate and schedule of 2',2' difluorodeoxycytidine (Gemcitabine) administration in leukemia. AB - The objective of this study was to determine the dose rate of 2',2' difluorodeoxycytidine (dFdC) that maximizes the accumulation of the active 5' triphosphate (dFdCTP) in circulating leukemia cells during therapy. The investigational approach was to evaluate the relationship between plasma dFdC and the accumulation of dFdCTP by circulating leukemia cells during infusion of different dFdC dose rates in the same individuals. Four patients with relapsed leukemia were treated weekly with two or three consecutive infusions of 800 mg/m2, the first administered over 1 h, the second over 2 h, and the third over 3 h. Two patients, one with acute myelogenous leukemia and one with acute lymphocytic leukemia, received all three infusions, but thrombocytopenia prohibited infusion of the third dose to two patients with chronic lymphocytic leukemia. The average steady-state plasma dFdC levels, achieved within 15 min after the infusion began, were 43.8 microM during infusion of 800 mg/m2/h, 9.4 microM during infusion of 400 mg/m2/h, and 5.6 microM at 267 mg/m2/h. The median area under the concentration times time curve of dFdCTP in leukemia cells during infusion was increased 2.3- and 5.1-fold for the 2- and 3-h infusions, respectively. In vitro incubations of leukemia cells from the four patients with 2.5-100 microM dFdC for 1 h showed that the maximum cellular accumulation of dFdCTP was produced by 15-20 microM dFdC. We conclude that a dose rate of greater than 400 mg/m2/h was required to achieve plasma dFdC levels that supported the maximum rate of dFdCTP accumulation in leukemia cells. PMID- 2208148 TI - ras gene mutations in human prostate cancer. AB - Point mutations at codons 12, 13, or 61 of the Ha-, Ki-, and N-ras genes are able to convert these normal cellular genes into activated oncogenes. Previous studies have shown that ras gene mutations occur in a variety of human solid tumors and may be important in the pathogenesis of some of these tumors. In order to test the hypothesis that ras gene mutations may be associated with prostate cancer, we have used an oligodeoxynucleotide hybridization assay to detect wild-type and mutant alleles in genomic DNA from prostate tumors and prostate tumor cell lines amplified using the polymerase chain reaction. Twenty-four primary prostate tumors (23 acinar tumors and one ductal tumor) and five prostate tumor cell lines were examined for mutations at codons 12, 13, and 61 of the Ki-ras, Ha-ras, and N ras genes. Two mutations were detected: an A----G transition causing a glutamine to arginine amino acid substitution at codon 61 of the Ha-ras gene in a primary prostatic duct adenocarcinoma and a G----T transversion causing a glycine to valine amino acid substitution at codon 12 of the Ha-ras gene in a prostate tumor cell line (TSU-PR1) derived from a lymph node metastasis. While the overall frequency of ras gene mutations in prostate tumors is low, when these mutations do occur they may have a role in the progression of disease or the development of the unusual ductal variant of prostatic adenocarcinoma. PMID- 2208149 TI - Phase II study of oral idarubicin in favorable histology non-Hodgkin's lymphoma. AB - Idarubicin, a new analogue of daunorubicin, was administered p.o. for 3 consecutive days every 3 weeks at a dose of 45 mg/m2 in 46 patients (45 eligible and evaluable) with previously treated, favorable histology, non-Hodgkin's lymphoma. Median clinical characteristics included an age of 66 years, a performance status of 1, and one prior chemotherapeutic regimen. Forty-one patients were relapsing from prior therapy, and 37 had stage IV disease. Patients with prior anthracycline therapy were excluded. Responses were observed in 58% of patients (10 complete and 16 partial), with a median duration of 6+ months (2-41+ months). Idarubicin was well tolerated. Nonhematological toxicities (nausea/vomiting, mucositis/diarrhea, alopecia, and anorexia) were observed in less than or equal to 50% of patients. Median hematological values during the first cycle include a WBC of 4100/mm3 and a platelet count of 147,000/mm3. With dose escalation, hematological toxicity was the dose-limiting toxicity. Symptomatic cardiac toxicity was not observed. Median values for the resting left ventricular ejection fraction during the course of therapy were 0.65 (initial) and 0.63 (final). Idarubicin in oral form is an active drug in previously treated patients with favorable histology non-Hodgkin's lymphoma. PMID- 2208150 TI - Diet, tobacco use, and fatal prostate cancer: results from the Lutheran Brotherhood Cohort Study. AB - A cohort of 17,633 white males age 35 and older responded to a mailed epidemiological questionnaire in 1966 and was followed until 1986 to determine the risk of cancer associated with diet, tobacco use, and other factors. During the 20-year follow-up, 149 fatal prostate cancer cases were identified. Relative risks for prostate cancer were significantly elevated among cigarette smokers (relative risk, 1.8; 95% confidence interval, 1.1-2.9) and users of smokeless tobacco (relative risk, 2.1; 95% confidence interval, 1.1-4.1). No significant associations were found with frequency of consumption of meats, dairy products, fruits, or vegetables. There were no overall significant associations between consumption of vitamin A from animal sources (retinol) and provitamin A from plant sources (carotene) and risk, but positive trends were seen for ages under 75, while inverse associations were found at older ages. Beverage consumption, including drinking coffee and alcohol, was unrelated to risk. Marital status, education, rural/urban status, and farming residence were also unrelated to the risk of fatal prostate cancer. The findings add to limited evidence that tobacco may be a risk factor for prostate cancer, but fail to provide clues to dietary or other risk factors. PMID- 2208151 TI - Glutathione transferase activity and isoenzyme composition in primary human breast cancers. AB - The human glutathione transferases (GSTs) are a multigene family of detoxication enzymes with patterns of expression that are both tissue specific and genetically determined. Changes in the levels of one or more GST isoenzymes have been associated with the development of anticancer drug resistance in cultured cell lines. In this study, total GST activity and GST isoenzyme composition have been determined for 45 primary human breast carcinomas using a 1-chloro-2,4 dinitrobenzene substrate assay and Western blotting, respectively. The GST activity ranged from 5-208 mU/mg protein with a mean of 67 mU/mg protein (+/- 44 SD). GST-pi) isoenzyme protein was detectable on Western blots in 44 of 45 samples. Mu Class GST protein was detected in 18 of 38 samples and undetectable in 20 of the 38 samples tested. By polymerase chain reaction analysis of genomic DNA, the absence of mu class GST in breast tumors was determined to be due to the deletion of the gene for GST-mu in the DNA of those tumors. None of the 43 primary human breast cancer samples tested contained detectable alpha class GST protein. Neither the total GST activity of tumor samples, the quantity of GST-pi protein, nor the presence or absence of mu class GST correlated with other factors known to be of prognostic significance including tumor size, nodal status, estrogen receptor protein positivity, or progesterone receptor protein positivity. Substantial differences exist among primary breast carcinomas in both the amount of GST activity and GST isoenzyme composition. However, these are not tightly linked either to tumor stage or to hormone receptor status. Whether the levels of these enzymes are independent predictors of either risk of recurrence or response to anticancer therapy has yet to be tested directly. PMID- 2208152 TI - Prospective evaluation of a model for predicting etoposide plasma protein binding in cancer patients. AB - Etoposide protein binding in cancer patients is variable and has been related mathematically to a linear model consisting of serum albumin and total bilirubin [percentage unbound = (1.4 x total bilirubin) - (6.8 x albumin) + 34.4]. In this prospective evaluation of the model, plasma samples were obtained following the administration of etoposide in 31 patients, and the unbound percentage (% unbound) of etoposide in plasma was determined by equilibrium dialysis. The mean measured % unbound was 15.3 +/- 11.6 (SD), and the mean model predicted % unbound was 16.7 +/- 10.1. The relation between predicted and measured etoposide % unbound was highly correlated (r2 = 0.92, P = 0.001). The model was precise but with a slight bias toward overpredicting % unbound (mean prediction error, 1.36%; 95% confidence interval, 0.09 to 2.6%). In patients with abnormal total bilirubin (i.e., greater than 1.5 mg/dl) or with hypoalbuminemia (i.e., less than 3.3 g/dl), the model was both precise and unbiased. These results demonstrate that etoposide % unbound can be predicted using serum albumin and total bilirubin. This model should be useful in prospectively identifying patients at increased risk of experiencing altered pharmacological effects due to altered protein binding of etoposide. PMID- 2208153 TI - Structure-function studies on analogues of 1 alpha,25-dihydroxyvitamin D3: differential effects on leukemic cell growth, differentiation, and intestinal calcium absorption. AB - The hormonally active form of vitamin D, 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], is an efficient stimulator of intestinal calcium absorption (ICA) and bone calcium mobilization (BCM) in humans and experimental animals and, as well, has been shown to be effective in inducing differentiation and inhibiting proliferation of leukemia cells. Thus, it has been proposed that analogues of 1,25(OH)2D3 could be synthesized which might allow for separation of biological functions, i.e., promote a differentiation of leukemia cells without a significant stimulation of ICA or BCM, both biological effects which can cause hypercalcemia in humans. Here we report the results of an evaluation of four analogues of the previously studied (Zhou et al., Blood, 74:82-92, 1989) 1 alpha,25-dihydroxy-16-ene-23-yne-vitamin D3 [1,25(OH)2-16-ene-23-yne-D3]; these analogues allowed evaluation of the consequences of (a) the presence or absence of six deuterium atoms on carbons 26 and 27 of the side chain and (b) the deletion or substitution by a fluorine atom of the 1 alpha-hydroxyl group on the A-ring. The 1,25(OH)2-16-ene-23-yne-D3 analogue was found to be 7-fold more potent than the parent 1,25(OH)2D3 with respect to (a) inhibition of clonal proliferation of HL-60 cells as well as (b) induction of differentiation of HL-60 promyelocytes. Variants of this analogue which possessed the six deuterium atoms on carbons 26 and 27 were slightly less active than the 1,25(OH)2-16-ene-yne-D3. However, replacement of the 1 alpha-hydroxyl group by a 1-fluoro group, or the absence of the 1-hydroxyl group, resulted in analogues that were somewhat less effective than the parent 1,25(OH)2D3 in achieving these biological responses but more potent as inhibitors of the renal mitochondrial 25-OH-D3-1 alpha hydroxylase, the site of endogenous production of 1,25(OH)2D3. ICA and BCM were assessed in vivo in vitamin D-deficient chickens, and each of the analogues was markedly less potent than the standard 1,25(OH)2D3. The analogue 1,25(OH)2-16-ene 23-yne-D3 had 2% of the ICA and 3% of the BCM activity of the parent 1,25(OH)2D3. Absence of the 1 alpha-hydroxyl group or substitution of the 1-fluoro group for the 1-hydroxyl group significantly diminished both the ICA and BCM activity in comparison to 1,25(OH)2-16-ene-23-yne-D3. Receptor binding studies indicated that 1,25(OH)2-16-ene-23-yne-D3 competed about 75% as effectively as 1,25(OH)2D3 for 1,25(OH)2D3 receptors present in both chick intestinal cells and HL-60 cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2208154 TI - An MDBP site in the first intron of the human c-myc gene. AB - The expression of the human c-myc protooncogene is subject to many levels and types of control. Evidence suggests that regulation of the expression of this gene involves elements within the gene as well as those upstream from the gene. We show that a ubiquitous mammalian sequence-specific DNA-binding protein, MDBP, binds specifically to a site in the beginning of the first intron of this gene. This protein, which binds to certain viral enhancers, may be helping to control expression of the c-myc gene. In some Burkitt lymphomas, which contain activated c-myc genes, the MDBP site is lost by chromosome rearrangement or by multiple spontaneous mutations. This might contribute to cancer-related activation of this protooncogene. PMID- 2208155 TI - Determination of O6-butylguanine in DNA by immunoaffinity extraction/gas chromatography-mass spectrometry. AB - A sensitive, specific, and rapid method for quantitating the minor adduct O6 butylguanine (O6BuG) in hydrolyzed DNA has been developed by combining immunoaffinity chromatography and high resolution gas chromatography-negative ion chemical ionization-mass spectrometry. Polyclonal antibodies raised against O6BuG were coupled to CNBr-activated Sepharose 4B and used for sample clean-up and extraction of the specific O6-alkylguanine. After addition of O6BuG and its deuterium labeled analogue (O6BuG-D7), used as internal standard, hydrolyzed DNA was applied on the immunoaffinity column and washed with water, and the immunoadsorbed butylated guanines were eluted with acetone/water cetome/water (95/5) before gas chromatographic derivatization. O6BuG and O6BuG-D7 were analyzed and quantitated by high resolution gas chromatography-negative ion chemical ionization-mass spectrometry as their pentafluorobenzyl-trimethylsilyl derivatives. Immunoaffinity column capacity and O6BuG recovery from this column were 1.53 nmol O6BuG/column and 62 +/- 5%, respectively. The method was applied to evaluate O6BuG levels in DNA butylated in vitro with 10 mM N-nitroso-Nr butylurea or isolated from rats given an i.p. dose of 185 mg/kg N-nitroso-N butylurea or N-nitrosodibutylamine. In the first case the level of modifications present in calf thymus DNA was 104 mumol O6BuG/mol guanine, and in the second case O6BuG in liver DNA was about 6 times higher after N-nitroso-N-butylurea (2.11 mumol O6BuG/mol guanine) than after N-nitrosodibutylamine (0.34 mumol O6BuG/mol guanine) treatment. These results indicate that O6BuG formed in vivo can be isolated and quantitated by this method, which may also be useful for studying DNA damage and repair mechanisms. PMID- 2208156 TI - Survey of exposure to genotoxic agents in primary myelodysplastic syndrome: correlation with chromosome patterns and data on patients without hematological disease. AB - Exposure to genotoxic agents such as insecticides, pesticides, and solvents correlated with abnormal karyotypes and development of acute nonlymphocytic leukemia (ANLL) similar to, but to a lesser degree compared to, patients exposed to irradiation and alkylating drugs in several reports. Because of the natural progression of myelodysplastic syndrome (MDS) to ANLL, we investigated the relationship of exposure to these carcinogens in patients with primary MDS by having 52 such patients diagnosed and referred to our center answer an occupational/environmental questionnaire. We excluded all secondary MDS patients with exposure to previous chemotherapy and radiation for a previous malignancy. In addition, we prospectively gave the same questionnaire to a similar number of age- and sex-matched comparable control patients from the same socioeconomic group based on their residence, health insurance coverage, and occupation. We found a 46% exposure rate to implicated genotoxic agents in our patients with MDS. Patients with MDS who were exposed had 75% incidence of a poor prognosis French-American-British classification compared to 57% in the nonexposed group but the difference was not significant (P = 0.089). However, the karyotypic abnormalities that were associated with exposure in ANLL were found equally in both exposed (55%) and nonexposed groups (50%) of our MDS patients and our control group had a similarly high exposure rate at 40% to genotoxins. Implicating a relationship between exposure to pesticides and solvents in ANLL and MDS is difficult. All the previous studies indicating such a relationship did not use a control group of patients. Our findings indicate the pitfalls of historical data without investigating the bias of obtaining an exposure history. However, our findings that the majority of our MDS patients came from the middle socioeconomic group which has a high exposure rate as shown by our control group indicate a relationship and that prospective follow-up of the exposed cohort of control patients should be done to determine if ANLL and MDS will increase after a latent period compared to the nonexposed controls. PMID- 2208158 TI - Antitumor efficacy of vaccinia virus-modified tumor cell vaccine. AB - The antitumor efficacies of vaccinia virus-modified tumor cell vaccines were examined in murine syngeneic MH134 and X5563 tumor cells. UV-inactivated vaccinia virus was inoculated i.p. into C3H/HeN mice that had received whole body X irradiation at 150 rads. After 3 weeks, the vaccines were administered i.p. 3 times at weekly intervals. One week after the last injection, mice were challenged i.p. with various doses of syngeneic MH134 or X5563 viable tumor cells. Four methods were used for preparing tumor cell vaccines: X-ray irradiation; fixation with paraformaldehyde for 1 h or 3 months; and purification of the membrane fraction. All four vaccines were effective, but the former two vaccines were the most effective. A mixture of the membrane fraction of untreated tumor cells and UV-inactivated vaccinia virus also had an antitumor effect. These results indicate that vaccine with the complete cell structure is the most effective. The membrane fraction of UV-inactivated vaccinia virus-absorbed tumor cells was also effective. UV-inactivated vaccinia virus can react with not only intact tumor cells but also the purified membrane fraction of tumor cells and augment antitumor activity. PMID- 2208157 TI - Nonassociation of aflatoxin with primary liver cancer in a cross-sectional ecological survey in the People's Republic of China. AB - A comprehensive cross-sectional survey was undertaken in The People's Republic of China of possible risk factors for primary liver cancer (PLC) to include 48 survey sites, an approximately 600-fold aflatoxin exposure range, a 39-fold range of PLC mortality rates, a 28-fold range of hepatitis B virus surface antigen (HBsAg+) carrier prevalence, and estimation of exposures for a large number of other nutritional, dietary, and life-style features. PLC mortality was unrelated to aflatoxin intake (r = -0.17) but was positively correlated with HBsAg+ prevalence (P less than 0.001), plasma cholesterol (P less than 0.01), frequency of liquor consumption (P less than 0.01), and mean daily intake of cadmium from foods of plant origin (P less than 0.01). Multiple regression analyses for various combinations of risk factors showed that aflatoxin exposure consistently remained unassociated with PLC mortality regardless of variable adjustment. In contrast, associations of PLC mortality with HBsAg+, plasma cholesterol, and cadmium intake remained, regardless of model specification, while the association with liquor consumption was markedly attenuated (was nonsignificant) with adjustment for plasma cholesterol. The sharp contrast between the findings of no aflatoxin effect upon PLC prevalence in this survey and the positive correlation reported for previous but more restricted surveys is discussed. Based on the results of this survey and the data of laboratory animal and in vitro studies, an explanatory model for the etiology of PLC is proposed, taking into consideration the role of nutrition in the etiology of this disease. PMID- 2208160 TI - Stable expression of human aromatase complementary DNA in mammalian cells: a useful system for aromatase inhibitor screening. AB - A mammalian cell expression plasmid, pH beta-Aro, containing the human placenta aromatase complementary DNA was constructed. The prepared plasmid was used to transfect breast cancer cells (MCF-7), noncancerous breast cells (HBL-100), and Chinese hamster ovary cells by a stable expression method. While the maximum velocities for aromatase expressed in three types of cells were different (10-201 pmol of [3H2O] formed/h/mg) using [1 beta, 2 beta-3H]androst-4-ene-3,17-dione as the substrate, the apparent Michaelis-Menten constants were found to be similar (39.9-57.8 nM) and were within the range determined for the enzyme existing in human placenta. The expressed activities were inhibited by the known aromatase inhibitors, 4-hydroxyandrostenedione and aminoglutethimide, at concentrations that normally inhibit the human placental aromatase. However, it was found that the inhibition profiles were different for aromatase expressed in different types of cells, suggesting that other factors, such as the uptake of the inhibitor, may also play a role in determining the inhibition efficiency. These constructed aromatase expressing mammalian cell lines will be very useful tools for aromatase inhibitor screening. PMID- 2208159 TI - Action of gossypol and rhodamine 123 on wild type and multidrug-resistant MCF-7 human breast cancer cells: 31P nuclear magnetic resonance and toxicity studies. AB - The action of gossypol, a polyphenolic bisnaphthalene aldehyde, on a number of drug-sensitive and multidrug-resistant cell lines, in particular MCF-7 WT and MCF 7 ADR cells, was studied and compared to the effects of rhodamine 123. 31P nuclear magnetic resonance spectra of cells exposed to low concentrations of gossypol exhibited decreased levels of ATP, markedly increased levels of pyridine nucleotides, and decreased levels of glycerylphosphocholine. The latter effect may be related to the membrane viscosity-increasing effect of gossypol, whereas changes in the levels of pyridine nucleotides are probably due to an interference with NAD- and NADP-dependent enzymes. The effect of gossypol represents a rare example of selective and differentiated changes observed in 31P nuclear magnetic resonance spectra of cells following exposure to a drug; the effect was markedly different from that of rhodamine 123, which caused ATP depletion but no changes in the levels of glycerylphosphocholine or pyridine nucleotides. Also, the effects of gossypol and rhodamine 123 on glucose metabolism in the MCF-7 WT cells were different. Thus although both drugs caused a marked elevation of glucose uptake, an increase in lactate production exceeding that of glucose consumption, indicating an inhibition of oxidative phosphorylation, was observed only in the case of rhodamine 123. Significantly, multidrug-resistant cells exhibited strong cross-resistance to rhodamine but practically no resistance to gossypol, which emphasizes the attractiveness of the latter as a potential anticancer drug. The resistance to rhodamine 123 and sensitivity to gossypol was also observed with cells transfected with the MDR1 gene, showing that the difference in toxicity is mainly due to the different response to the P-170 drug efflux pump. PMID- 2208161 TI - Promotion of colonic microadenoma growth in mice and rats fed cooked sugar or cooked casein and fat. AB - We studied the effect of cooked food components on the promotion of microadenoma growth in the colons of mice and rats. CF1 mice and Fisher 344 rats were initiated with azoxymethane, with 152 mice receiving four weekly i.p. injections of 5 mg/kg, 59 rats receiving a single injection of 20 mg/kg, and 24 rats receiving 30 mg/kg. A week after the last injection, the animals were randomly assigned to one of eight diets with identical ingredients, but the three components, sucrose, casein, and beef tallow, either uncooked or cooked. Control animals were given diets with uncooked ingredients. Experimental animals were fed diets in which one, two, or three of the components were cooked in an oven at 180 degrees C until golden brown before they were added to the diet. After 100 days on the diets, the colons were fixed, stained with methylene blue, and scored for microadenomas. The mice and the rats fed cooked sucrose, or casein and beef tallow cooked together, had three to five times more large microadenomas than did the controls (P ranging from 0.02 to 0.0001). No significant increase was observed with the five other cooked diets. Two rats fed the casein and beef tallow cooked together had adenocarcinomas. Thus, a diet containing 20% of cooked sucrose, or 40% of casein and beef tallow cooked together, promotes the growth of colonic microadenomas in initiated mice and rats, and would appear to contain promoters for colon cancer. PMID- 2208162 TI - Constitutive production of interleukin 6 by ovarian cancer cell lines and by primary ovarian tumor cultures. AB - We examined the production and utilization of interleukin 6 (IL-6), a multifunctional cytokine with diverse biological effects, by both ovarian cancer cell lines and primary ovarian tumor cultures. We have found that epithelial ovarian cancer cell lines (CAOV-3, OVCAR-3, and SKOV-3) constitutively produce varying amounts of IL-6. This molecule is biologically active as determined by the proliferation of an IL-6-dependent hybridoma cell line, MH60.BSF-2, and is detectable by an IL-6 enzyme-linked immunosorbent assay. By cytoplasmic immunoperoxidase staining, greater than 98% of the cells produce at least some IL 6, with variation in the staining intensity between individual cells. The ovarian cancer cell-produced protein has a molecular weight of approximately 24,000, and exhibits some molecular weight heterogeneity, with Mr 27,000 and 28,000 minor forms of IL-6. The levels of IL-6 produced by ovarian cancer cells can be modulated by other inflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1 beta, and interferon-gamma. Our results suggest that IL-6 is not an autocrine growth factor for these established ovarian tumor cell lines, because the addition of either exogenous IL-6 or antibodies to IL-6 did not affect the cellular proliferation of the cell lines. We also found significant levels (greater than 3 ng/ml) of IL-6 in ascitic fluids of ovarian cancer patients and in the supernants of primary cultures from freshly excised ovarian tumors. The production of IL-6 by epithelial ovarian cancer cells may prove to be a useful diagnostic tool and aid in investigation of the host immune response to ovarian cancer. PMID- 2208163 TI - Cytotoxicity, radiosensitization, antitumor activity, and interaction with hyperthermia of a Co(III) mustard complex. AB - A complex of Co(III) with a nitro group and a bis(2-chloroethyl)amine moiety was prepared in an effort to develop a new anticancer agent with radiosensitizing capabilities, direct antitumor activity, and the ability to interact positively with clinically relevant hyperthermia temperatures. The activity of this drug was compared to a similar Co(III) complex, nitro-bis(2,4 pentanedionato)(pyridine)cobalt(III) [Co(Py)], which bears a pyridine moiety mustard of bis(2-chloroethyl)amine and should have no alkylating abilities. In EMT6 cells nitro-bis(2,4- pentanedionato)(bis(2-chloroethyl)amine)cobalt(III) [Co(BCA)] was significantly more cytotoxic than Co(Py) and both drugs were more toxic toward normally oxygenated than hypoxic cells. Hyperthermia (42 degrees C, 1 h) increased the slope of the concentration-dependent survival curve for Co(BCA) but not for Co(Py) in normally oxygenated EMT6 cells. Co(BCA) was an effective radiosensitizer of hypoxic EMT6 cells in vitro, producing a dose modifying factor of 2.40. In the human squamous cell line SCC-25 and the nitrogen mustard-resistant subline SCC-25/HN2 Co(BCA) was more cytotoxic than Co(Py), and the lethality of Co(BCA) was only minimally diminished in the SCC-25/HN2 line. In mice bearing the L1210 leukemia i.p., Co(BCA) had a broad range of therapeutically effective dosage and produced a greater than 60-day increase in life span at a dose 20-fold less than was lethally toxic. In addition, in the FSaIIC murine fibrosarcoma, Co(BCA) produced a tumor growth delay of 9.4 days at 75 mg/kg i.p. daily x 5, but Co(Py) produced a delay of only 2.9 days at 50 mg/kg daily x 5 and was lethally toxic above this dose. These results indicate that Co(BCA) has significant antineoplastic effects in vitro and in vivo and interacts positively with both radiation and mild hyperthermia. Its broad therapeutic dose range further suggests potential clinical utility. PMID- 2208164 TI - Glutathione content and glutathione-S-transferase expression in 1,3-bis(2 chloroethyl)-1-nitrosourea-resistant human malignant astrocytoma cell lines. AB - gamma-L-glutamyl-L-cysteinylglycine (GSH) has been shown to inactivate 1,3-bis(2 chloroethyl)-1-nitrosourea (BCNU) and quench DNA crosslink precursors of BCNU. Because of the central role of 2-chloroethyl-nitrosoureas in brain tumor chemotherapy, we investigated the intracellular GSH content and the expression of specific glutathione-S-transferases (GSTs) in three human malignant astrocytoma cell lines (UWR1, UWR2, and UWR3) of varying BCNU resistance to determine the interrelationship of these parameters with brain tumor BCNU resistance. GSH was assayed by ion-exchange high performance liquid chromatography after derivatization with 1-fluoro-2,4 dinitrobenzene. Both bulk and specific GST (acid, near-neutral, and basic) activities were examined using substrates that show high specificities to the different GSTs. Western blot analyses with antisera against GST-alpha, -mu, and -tau subunits were also performed on partially purified GST from the cells of each cell line. The results showed GSH content of 91, 46.5, and 28.3 nmol GSH/mg protein for UWR1, UWR2, and UWR3, respectively. Bulk GST activity (with 1-chloro-2,4-dinitrobenzene as substrate) also correlated with increasing BCNU resistance. Of the three GST classes examined by both substrate specificities and Western blotting, only the expression of the acidic form, GST-tau, correlated significantly with the rank order of BCNU resistance of the cell lines. GST-mu and -alpha were present in only trace amounts in all three cell lines. PMID- 2208165 TI - Melanoma-inhibiting activity inhibits cell proliferation by prolongation of the S phase and arrest of cells in the G2 compartment. AB - Autocrine-secreted melanoma tumor growth-inhibiting activity (MIA, approximately Mr 8000) was isolated from supernatants of a malignant melanoma cell line HTZ-19 dM, established from a central nervous system-melanoma metastasis. Cell cycle kinetic analysis performed with bromodeoxyuridine/Hoechst flow cytometry revealed a MIA-sensitive period at the G0/G1 to S traverse; MIA mediated prolongation of the S-phase and increased arrest of cells in the G2 compartment. Growth inhibition by MIA is cell-density dependent; maximal effect is seen at low densities, and the effect may be partially antagonized by whole serum. MIA may cause growth stimulation at high cell densities and low MIA concentrations. The effect of MIA on different histological neuroectodermal cell types was compared by the same methodology: proliferation of a second malignant melanoma was inhibited, and no effect was observed with an ependymoma; 2 glioblastomas were slightly stimulated. Effects on human fibroblast-like cell strains were inconsistent. The mechanism of MIA is discussed in relation to other endogenous autocrine growth inhibitors. PMID- 2208167 TI - Characterization of new human pancreatic cancer cell lines which propagate in a protein-free chemically defined medium. AB - Many human cancer cell lines which have been maintained in fetal bovine serum (FBS)-supplemented medium produce and secrete many substances such as transferrin, alpha 1-antitrypsin, alpha 2-macroglobulin, alkaline phosphatase, gamma-glutamyltranspeptidase, creatine kinase, carcinoembryonic antigen, alpha fetoprotein, carbohydrate antigen 19/9, and cytokines including colony stimulating factors and transforming growth factor, and further they may produce small amounts of unknown substances. Usually, small amounts of substances have to be concentrated as highly as possible for detection, but FBS interferes with this procedure. A protein-free culture system is an ideal method for detecting small quantities of substances which originate from cancer cells without interference by FBS. However, we were concerned that protein-free culture may interrupt the production of the substances which have been produced in FBS-supplemented medium. In this study, we investigated the productibility of 46 kinds of well-known substances in ten newly established cell lines derived from human pancreatic cancer. These cell lines were propagated in a protein-free non-FBS-supplemented medium. Of the ten cases, one cell line alone that was derived from acinal cell carcinoma propagated as a semisuspension; on the other hand, nine cell lines that were derived from ductal cell carcinoma propagated as monolayers without piling up. This method prolongs the doubling time, which is not affected by the addition of FBS. The spent media of these cell lines were collected aseptically after the removal of cell debris and concentrated by ultrafiltration using a Pericon cassette followed by lyophilization. Using 46 kinds of available antibodies, we investigated whether or not the substances which react to these antibodies could be detected in the spent media and in the cells by enzyme-linked immunosorbent assay, Western blot analysis, and immunocytochemistry. Among these cell lines, HPC-Y11 produced and secreted the most kinds of substances, and the production of those substances was lowest in HPC-Y0. In conclusion, our protein-free culture system can be available in every laboratory, since this is not only an economical method, but also an effective method for the saving of purification procedures. Moreover, this is a most suitable method for surveying unknown substances derived from cancer cell lines. PMID- 2208166 TI - Application of an interleukin 2 slow delivery system to the immunotherapy of established murine colon 26 adenocarcinoma liver metastases. AB - We evaluated the antitumor effect of an interleukin 2 (IL-2) slow delivery system, the IL-2 minipellet, using a murine hepatic metastasis model. The IL-2 minipellet consists of atelocollagen derived from natural bovine skin together with 1 x 10(6) units of recombinant IL-2. Administration of the IL-2 minipellet was performed into the spleens of BALB/c mice after translocation of the spleens to the s.c. position. Administration produced detectable serum IL-2 levels for 72 h. The IL-2 minipellet was evaluated for its efficacy against hepatic metastases from colon 26 adenocarcinoma in the BALB/c mice. Both the administration of the IL-2 minipellet alone and its combination with the injection of 5 x 10(7) lymphokine-activated killer cells resulted in significant reductions of the number of metastatic nodules. Moreover, increased survival of mice bearing colon 26 adenocarcinoma was noted in these two treatment groups. To investigate the mechanism of the IL-2 minipellet activity, we tested the lytic potential of splenocytes obtained after administration of the IL-2 minipellet in a 51Cr release assay. Cytotoxicity against YAC-1 cells and colon 26 cells was significantly augmented on Day 2 after minipellet administration. These results demonstrated that local administration of the IL-2 minipellet into the hepatic circulation was extremely effective against metastatic liver cancer. PMID- 2208168 TI - Phenobarbital enhances the formation of reactive oxygen in neoplastic rat liver nodules. AB - The effect of treatment of rats with the liver monooxygenase inducer phenobarbital on the formation of reactive oxygen in neoplastic liver nodules and the surrounding normal tissue was investigated. Liver nodules were induced by treatment of rats with diethylnitrosamine (single i.p. injection of 0.15 mumol/kg body weight on day 1 after birth) followed by chronic administration of phenobarbital-sodium (PB; 0.05% in diet) after weaning. Groups of rats were kept on PB until sacrifice or were withdrawn from the promoter 3-6 weeks prior to killing. Emission of chemiluminescence was used as a sensitive means to detect the formation of reactive oxygen in microsomal preparations from the various tissues incubated with NADPH and the chemiluminigenic detector lucigenin. In addition, a 2-dimensional photon counting system has been developed that permits the analysis of the spatial distribution of lucigenin-chemiluminigenic signals over liver tissue sections incubated with reduced phosphopyridine dinucleotides. In general, we observed increased levels of reactive oxygen formation in liver nodules when compared with the normal liver tissue. Highest levels were seen in nodules that stemmed from PB-induced rats. Studies on the expression and activity of cytochrome P-450 in liver nodules as well as experiments with specific inhibitors point towards a participation of the liver monooxygenase system in reactive oxygen formation, although additional metabolic pathways seem to be involved as well. The observed increases in reactive oxygen in liver nodules of PB-treated rats might be related to the promoting activity of this drug. PMID- 2208169 TI - Induction of replicative competence ("priming") in normal liver. AB - We have used a system of nutritional manipulation to investigate whether hepatocytes of the normal liver can be primed for replication in vivo. In this system, rats that are denied protein for 3 days undergo a burst of hepatic DNA synthesis and mitosis when they are refed amino acids, while normally fed or starved rats do not respond. To determine if hepatocytes of protein deprived (PD) rats have been "primed" for replication, we examined changes in protooncogene expression in livers of PD rats to see if they would mimic the pattern of gene expression that is induced early after partial hepatectomy. c-jun, c-myc, and p53 mRNAs were elevated in livers of PD rats, while c-fos and c-ras genes were not expressed. The administration of amino acids to PD rats stimulated hepatic DNA synthesis in a shorter period than is required after partial hepatectomy and induced p53 and c-ras expression. In culture, hepatocytes from PD rats had higher levels of c-myc mRNA, underwent morphological changes more rapidly, and reached maximum rates of DNA synthesis earlier than normal hepatocytes. In both normal and primed hepatocyte cultures, transforming growth factor alpha stimulated DNA synthesis more effectively than epidermal growth factor. We conclude that hepatocytes pass through a priming stage before they proliferate and that replicative competence without DNA synthesis can be induced in hepatocytes in the normal liver. PMID- 2208170 TI - Selective reduction of cis-diamminedichloroplatinum(II) nephrotoxicity by ebselen. AB - 2-Phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen) is classified as a relatively nontoxic selenium compound, probably because of its bound selenium moiety. In thiol-rich tissues, such as the kidneys, ebselen is converted into selenol intermediates. Selenols are nucleophilic agents which might be able to react with platinum compounds. The influence of ebselen on cis-diamminedichloroplatinum(II) (cisplatin)-induced nephrotoxicity in mice was assessed, using single doses of both compounds. Ebselen prevented cisplatin-induced elevations of blood urea nitrogen and serum creatinine levels and morphological kidney damage in BALB/c mice. This protective effect of ebselen was dose dependent: at a cisplatin dose of 14.5 mg/kg, maximal protection was achieved when a single dose of 10 mg of ebselen/kg was administered 1 h before cisplatin. Administration of ebselen, 10 mg/kg, 1 h after cisplatin also protected against severe nephrotoxicity. Treatment with ebselen did not reduce the antitumor activity of cisplatin against MPC 11 plasmacytoma or Prima breast tumor in BALB/c mice. However, this reduction of cisplatin-induced nephrotoxicity would be of little clinical value if it was achieved at toxic doses of ebselen. Ebselen, 10 mg/kg, did not induce blood urea nitrogen, serum creatinine, serum glutamic pyruvate transaminase, or serum glutamic oxalate elevations in the mice. These results are in agreement with the reported low toxicity of ebselen, which is now in Phase I clinical trials as an antiinflammatory drug. The present results indicate that ebselen may provide protection against cisplatin-induced nephrotoxicity, when it is given before or after cisplatin. This might open new perspectives in cancer chemotherapy. PMID- 2208171 TI - A murine model for B-cell lymphomagenesis in immunocompromised hosts: c-myc rearranged B-cell lines with a premalignant phenotype. AB - Activation of c-myc or bcl-2 protooncogene is a common event in B-cell lymphomagenesis. Alone, each is insufficient to produce lymphoma, prompting the search for the additional steps required to complete the malignant phenotype. Among the existing systems of murine or human B-cell neoplasia, no commonly occurring complementary oncogenic activation has been found. This study introduces a new series of murine B-cell lines with a phenotype suggesting that such additional events might not involve intrinsic growth control, but instead host immune mechanisms which normally suppress tumorigenicity of premalignant B cells. Four murine B-cell lines were isolated from the long-term culture of normal lymphoid tissue bearing a premalignant phenotype. (a) Their phenotype resembled naturally occurring lymphoid tumors of immunocompromised hosts with regard to c-myc activation, aberrant or absent immunoglobulin expression, preferential rearrangement of the lambda light chain locus, and a distinctive pattern of tissue invasion and tumor histology. (b) Their tumorigenicity was strictly dependent on host permissiveness correlated with immunodeficient status: C.B-17-scid greater than BALB/c-nu/nu greater than normal BALB/c much greater than other H-2d strains (NZB x NZW F1, NZB, DBA/2). (c) Host passage selected for malignant variants distinguished by a 10(4)-fold increase in tumorigenicity (as judged by limiting cell dose) and by novel tumorigenicity in nonpermissive syngeneic hosts. These features are analogous to properties of human lymphomas arising in immunocompromised states and, to our knowledge, unique among previously reported murine B-cell lines. PMID- 2208172 TI - A murine model for B-cell lymphomagenesis in immunocompromised hosts: natural killer cells are an important component of host resistance to premalignant B-cell lines. AB - The accompanying paper (D. W. Felsher et al., Cancer Res., 50:7042-7049, 1990) describes a new panel of cloned murine B-cell lines with a premalignant phenotype and in vivo-derived malignant variants. This paper assesses the contribution of immune mediated antitumor mechanisms which might account for host resistance to the tumorigenicity of these cell lines. Conventional T-cell-dependent responses did not appear to be critical to host resistance. In vivo elimination of T-helper cells with anti-L3T4 monoclonal antibody did not reduce host resistance to the tumorigenicity of these cell lines, nor did these cell lines elicit cytotoxic T cell activity. However, a strong correlation was found between tumorigenicity and host natural killer (NK) activity. In vitro studies demonstrated that the cell lines were as NK sensitive as the prototypical NK target, YAC-1, whereas the malignant variants fully tumorigenic in normal hosts were greater than 20-fold less NK sensitive than were the parent cell lines. In vivo depletion of NK cells with anti-asialo-GM1 in BALB/c strongly diminished host resistance to cell line tumorigenicity, whereas polydeoxyinosinic-deoxycytidilic acid induction of NK cells enhanced host resistance. These findings indicate that NK function is a critical component to host resistance in this system and suggest that endogenous cellular mechanisms which overcome NK sensitivity could be a target for secondary transforming events in B-cell lymphomagenesis. They also raise the unexpected possibility that a non-antigen-dependent (versus immune cytotoxic T-lymphocytes) effector mechanism may be the key deficit promoting B-cell neoplasia in the setting of immunocompromised states. PMID- 2208173 TI - Immunocytochemical localization of estrogen and progesterone receptor and prognosis in human primary breast cancer. AB - An immunocytochemical assay (ICA) for the measurement of estrogen receptor (ER) and progesterone receptor (PgR) has been evaluated in 426 human primary breast carcinomas. For estrogen receptor determination ER ICA was used. PgR ICA was performed using the monoclonal antibody KD 68. Assay results for progesterone receptor immunocytochemistry were in agreement (P less than 0.0001) with those of biochemical determination in 74%. Progesterone receptor positivity determined with a semiquantified approach based on intensity and heterogeneity of immunocytochemical staining correlated significantly with biochemically determined progesterone receptor levels (P = 0.0001). Survival data showed a significantly better overall survival for patients with either ER ICA- or PgR ICA positive carcinomas (ER ICA, P less than 0.00001; PgR ICA, P = 0.004). Patients with both negative ER ICA and PgR ICA showed a poorer prognosis than patients with only one negative receptor. In ER ICA- and PgR ICA-positive carcinomas a trend could be found that patients whose carcinomas contained high numbers of receptor-positive tumor cells had a better survival. This study demonstrates that ER ICA and PgR ICA are strong prognostic indicators and that the proportion of steroid hormone receptor-positive tumor cells seems to be of clinical importance. PMID- 2208174 TI - In vitro malignant conversion of low-grade rat urinary bladder carcinoma cells by exposure to N-methyl-N-nitrosourea. AB - The cause of deeply invasive human bladder carcinoma is unknown. Animal studies suggest that a malignant (invasive) conversion is inducible in low-grade noninvasive tumors by further exposure to a chemical carcinogen. To elucidate what molecular mechanism(s) is involved in the conversion, an in vitro system has been established in which conversion from low- to high-grade carcinoma can be induced. A rat bladder carcinoma cell line D44, derived from an N-methyl-N nitrosourea (MNU)-induced low-grade noninvasive rat bladder carcinoma was used in the present investigation. Cloned D44 cells (D44c) were exposed to MNU, 50 to 400 micrograms/ml, for 1 h at 37 degrees C once a week for up to 6 weeks. After exposure to MNU, cells with altered morphology were cloned. The yield of altered clones was highest after a total dose of 150 to 200 micrograms of MNU used in 1 to 3 doses. Of 21 clones with altered morphology, 4 clones were further treated with MNU at the initial dose once a week for up to 3 weeks and then subcloned. Thirty-three of these subclones were examined for tumorigenicity in athymic nude mice. Twenty-seven formed highly invasive carcinomas, mostly squamous type, whereas the parental D44c cells failed to develop tumors upon inoculation. Pulmonary metastases were observed in 17 of the 27 clones. Plasminogen activator activity was elevated 4- to 9-fold as compared to parent D44c cells. ras p21 mutations at codon 12 were detected in 5 of 30 clones. These results indicate that the in vitro system described here may provide a useful model to study the molecular mechanisms involved in the conversion of noninvasive bladder carcinomas to metastasizing ones. PMID- 2208175 TI - Immunohistochemical evidence of autocrine growth factors in adenocarcinoma of the human lung. AB - We immunohistochemically examined 131 primary human lung adenocarcinomas for the possible presence of autocrine factors. Transforming growth factor alpha (TGF alpha) and epidermal growth factor (EGF) were considered growth factors with epidermal growth factor receptor (EGFR) as the receptor. Of these tumors, 87 (66%) showed a high expression of TGF alpha, 66 (50%) showed a high expression of EGF, and 55 (42%) were positive for EGFR reactivity. In the EGFR-positive cases, the 5-year survival rates of patients with high TGF alpha and low TGF alpha were 36% and 85%, respectively (P less than 0.05). The 5-year survival rates of patients with high EGF and low EGF were 25% and 77%, respectively (P less than 0.05). In contrast, in the EGFR-negative cases, there was no statistical difference between the 5-year survival rates of patients with either high TGF alpha or EGF and low TGF alpha or EGF. Because autocrine growth mechanisms are present in adenocarcinoma of the human lung, these events may contribute to clarification of tumor development, and perhaps even to a better prognosis. PMID- 2208177 TI - Cigarette smoking and stomach cancer. PMID- 2208176 TI - Allelic loss of chromosome 17p distinguishes high grade from low grade transitional cell carcinomas of the bladder. AB - Forty-three transitional cell carcinomas of the bladder of differing grades and stages were examined for reduction to homozygosity for chromosomes 9q, 11p, and 17p. Allelic loss of chromosome 9q was seen in 24 of 38 informative grades II, III, and IV tumors providing further evidence for a bladder tumor suppressor gene on this chromosome. In contrast to the grade-independent involvement of chromosome 9q, allelic losses of chromosomes 11p and 17p were seen only in grade III and IV tumors. The results with chromosome 17p were particularly striking and showed that 0 of 10 grade II versus 20 of 31 grade III and IV tumors had allelic losses for this chromosome harboring the p53 tumor suppressor gene often mutated in other human cancers. The data suggest that cumulative genetic damage is sustained in transitional cell carcinomas and that one of the underlying molecular mechanisms distinguishing low grade from high grade tumors involves chromosome 17p. PMID- 2208178 TI - U.S. Japan Seminar on molecular mechanisms of initiation, promotion progression. PMID- 2208179 TI - Thrombolytic agents in the treatment of stroke. PMID- 2208180 TI - Memory deficits of aged male rats can be improved by pyrimidine nucleosides and n acetyl-glutamine. AB - The pyrimidine nucleosides uridine (URI) and cytidine (CYT), alone or associated with n-acetyl-glutamine (NAG), were injected acutely or subchronically to aged (26 months old) male rats of the Sprague-Dawley strain. Learning and memory abilities of the animals were studied with tests of avoidance behavior. The acquisition of active avoidance behavior was studied with the shuttle-box test. A step-through type of passive avoidance task was used to examine the retention of passive avoidance responses. The acquisition of the active avoidance behavior and the retention of the passive avoidance response were reduced in aged animals as compared with those of young animals. Neither the acute treatment of old rats with URI and CYT alone nor that associated with NAG exerted any effect on the behavioral tests. In contrast, the subchronic treatment with URI and CYT was followed by a facilitation of acquisition of active avoidance behavior in the shuttle box and of retention of passive avoidance responses in the dark box. A more potent effect on the acquisition of the shuttle-box behavior and on the retention of passive avoidance reaction was found in animals treated subchronically with the pyrimidine nucleosides associated with NAG. These effects may be related to the role of pyrimidines in the synthesis of ribonucleic acid, which is indispensable for learning and memory processes. PMID- 2208182 TI - CQA 206-291: a novel dopamine agonist in the treatment of Parkinson's disease. AB - The antiparkinsonian efficacy and tolerability of CQA 206-291, a novel ergoline derivative with potent dopamine agonist properties, were studied during 2 months of treatment in 72 parkinsonian patients. In 36 de novo patients (patients who have not previously been treated with levodopa or dopamine agonists), CQA 206-291 was studied in an open design, while in 36 levodopa-treated patients, CQA 206-291 was studied in a randomized, double-blind, parallel-group, placebo-controlled design. CQA 206-291 induced in both groups a significant antiparkinsonian effect with an effective dose range of 5-30 mg/day. The spectrum of adverse events was similar to what is commonly observed with dopamine agonists. Further studies are required to assess the putative therapeutic advantages of CQA 206-291 when compared to other antiparkinsonian drugs. PMID- 2208181 TI - Immunoreactive beta-endorphin, cortisol, and growth hormone plasma levels in obsessive-compulsive disorder. AB - Basal morning plasma levels of immunoreactive-beta-endorphin (ir-beta-EP), cortisol, and growth hormone (GH) were assessed in 13 obsessive-compulsive disorder (OCD) patients in comparison to 20 healthy controls. All subjects were drug free for at least 1 year. The mean plasma level of ir-beta-EP was significantly lower (36%) in the OCD patients when compared with the control subjects. The decrease in ir-beta-EP was not accompanied by alteration in cortisol and GH plasma levels. PMID- 2208184 TI - EEG recordings following intrathecal iohexol administration. AB - Electroencephalogram (EEG) recordings were performed before and after intrathecal administration of iohexal (Omnipaque) in 30 patients who underwent cervical myelography or cisternography. Tracings were recorded before, several hours after, and 24 h after iohexol administration. No abnormalities were recorded. It can be concluded that iohexol is a safe contrast medium, having less encephalopathic effects than more commonly used substances such as metrizamide. PMID- 2208183 TI - Apomorphine in the diagnosis and treatment of parkinsonian tremor. AB - The response of rest tremor to single doses of subcutaneous apomorphine and oral levodopa was compared in 20 patients with tremor-dominant Parkinson's disease. In eight of these patients, who were experiencing refractory levodopa-induced fluctuations characterised by disabling tremor, we studied the efficacy of sustained subcutaneous apomorphine. Nineteen patients responded favourably to acute challenges of both apomorphine and levodopa, with abolition of tremor in 10. In three, the response was helpful in confirming the clinical diagnosis. Chronic apomorphine use led to a more than 50% reduction in tremor-filled hours per day. After a mean duration of follow-up of 7.5 months, there was no tachyphylaxis to its therapeutic action. Subcutaneous apomorphine is an effective adjunct in treating patients with resistant, tremor-dominant fluctuations, and may also be helpful in the diagnosis of parkinsonian tremor. PMID- 2208185 TI - Failure of fixed-dose, fixed muscle injection of botulinum toxin in torticollis. AB - We studied the effect of botulinum toxin injection in 30 patients with torticollis in a double-blind, placebo-controlled, crossover study. A fixed dose of toxin was injected into the contralateral sternocleidomastoid and both trapezius muscles. Clinical improvement was assessed by a rating scale and by patient self-evaluation. Subjective rating noted improvement in some patients, but there was no change in objective measures. The use of larger doses and injection of additional muscles may be necessary to achieve increased efficacy of botulinum toxin in the treatment of torticollis. PMID- 2208186 TI - 13C-N.M.R. spectra of cyclomalto-oligosaccharides (cyclodextrins), their derivatives, and complexes with azo dyes. AB - The nature of the inclusion complexes of several cyclomalto-oligosaccharides (cyclodextrins, CDs) with azo dyes has been studied on the basis of 13C-n.m.r. chemical shifts, relaxation times, correlation times, and broadening and doubling of the n.m.r. signals. All CDs show the azo dye-induced shifts at the narrow-rim side of the CD, indicating that the azo dyes protrude from the cavity. CD-induced shifts of azo dyes depend on the hydrophobic nature of the cavity, van der Waals forces, as well as ring-current and deformation effects, and suggest inclusion essentially from the hydrophobic site. The broadening and the doubling of the 13C n.m.r. signals, the altered relaxation and correlation times, as well as the temperature dependence for these phenomena, also provide particular information about the characteristic host-guest interactions. PMID- 2208187 TI - Isolation and characterization of three positional isomers of diglucosylcyclomaltoheptaose. AB - Three positional isomers of diglucosylcyclomaltoheptaose [(G)2-beta cyclodextrin], 6(1),6(4)-di-O-(a-D-glucopyranosyl)-cyclomaltoheptaose (1), 6(1),6(3)-di-O-(a-D-glucopyranosyl)-cyclomaltoheptaose (2), and 6(1),6(2)-di-O-(a D-glucopyranosyl)-cyclomaltoheptaose (3) were isolated by h.p.l.c. on a reversed phase column from the mother liquors of a large-scale preparation of beta CD with Bacillus ohbensis cyclomaltodextrin glucanotransferase (EC 2.4.1.19) and were characterized by h.p.l.c. analysis of partial hydrolyzates and by 13C-n.m.r. spectroscopy. Their molecular weights were confirmed by f.a.b.-m.s. Their characteristic chromatographic behavior on four h.p.l.c. columns of different separation modes was found to be very useful for their identification. It is particularly noteworthy that the first application of a graphitized carbon column to CDs enabled a fine separation of all three positional isomers. PMID- 2208188 TI - 1-Alkoxyamino-1-deoxy alditols, useful u.v.-absorbing derivatives of neutral and acidic oligosaccharides. PMID- 2208189 TI - Synthesis of an appropriately protected core glycotetraoside, a key intermediate for the synthesis of "bisected" complex-type glycans of a glycoprotein. AB - A stereocontrolled synthetic route to a glycotetraoside, allyl O-(3,4,6-tri-O benzyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl)-(1--- -4)-O- (3,6-di-O-allyl 2-O-benzyl-beta-D-mannopyranosyl)-(1----4)-O-3, 6-di-O-benzyl-2-deoxy-2 phthalimido-beta-D-glucopyranosyl)-(1----4)-3-O- benzyl- 2-deoxy-6-O-p-methoxy phenyl-2-phthalimido-beta-D-glucopyranoside, an important intermediate for the synthesis of "bisected" complex type glycans of glycoproteins has been established by employing two glycosyl donors, 3,4,6-tri-O-benzyl-2-deoxy-2 phthalimido-beta-D-glucopyranosyl trichloroacetimidate and 4-O-acetyl-3,6-di-O allyl-2-O-benzyl-alpha-D-mannopyranosyl bromide, and a glycosyl acceptor, allyl O (3,6-di-O-benzyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl)-(1----4) -3-O- benzyl-2-deoxy-6-O-p-methoxyphenyl-2-phthalimido-beta-D-glucopyranoside. PMID- 2208190 TI - Synthesis of alpha-D-Manp-(1----3)-[beta-D-GlcpNAc-(1----4)]-[alpha-D-Manp+ ++-(1 ---6)] - beta-D-Manp-(1----4)-beta-D-GlcpNAc-(1----4)-[alpha-L-Fucp- (1----6)]-D- GlcpNAc, a core glycoheptaose of a "bisected" complex-type glycan of glycoproteins. AB - A synthesis of alpha-D-Manp-(1----3)-[beta-D-GlcpNAc-(1----4)]-[alpha-D-Manp++ + (1----6)]- beta-D-Manp-(1----4)-beta-D-GlcpNAc-(1----4)-[alpha-L-Fucp-( 1----6)] D- GlcpNAc was achieved by employing benzyl O-(3,4,6-tri-O-benzyl-2-deoxy-2 phthalimido-beta-D-glucopyranosyl)-(1--- -4)-O- (2-O-benzyl-beta-D mannopyranosyl)-(1----4)-O-(3,6-di-O-benzyl-2-deoxy-2 - phthalimido-beta-D glucopyranosyl)-(1----4)-3-O-benzyl-2-deoxy-6-O-p- methoxyphenyl-2-phthalimido beta-D-glucopyranoside as a key glycosyl acceptor. Highly stereoselective mannosylation was performed by taking advantage of the 2-O-acetyl group in the mannosyl donors. The alpha-L-fucopyranosyl residue was also stereoselectively introduced by copper(II)-mediated activation of methyl 2,3,4-tri-O-benzyl-1-thio beta-L-fucopyranoside. PMID- 2208191 TI - A regio- and stereo-controlled synthesis of beta-D-Glcp NAc6SO3-(1----3)-beta-D Galp6SO3-(1----4)-beta-D-GlcpNAc 6SO3- (1----3)-D-Galp, a linear acidic glycan fragment of keratan sulfate I. AB - A stereocontrolled synthesis of beta-D-GlcpNAc6SO3-(1----3)-beta-D-Galp6SO3-(1--- 4)-beta-D- GlcpNAc6SO3- (1----3)-D-Galp, was achieved by use of benzyl O-(2 acetamido-3,4 di-O-benzyl-2-deoxy-6-O-p-methoxyphenyl-beta-D- glucopyranosyl)-(1- --3)-O-(2,4-di-O-tert-butyldiphenylsilyl-beta- D- galactopyranosyl-(1----4)-O-(2 acetamido-3-O-benzyl-2-deoxy-6-O-p-methox yphenyl - beta-D-glucopyranosyl)-(1--- 3)-2,4,6-tri-O-benzyl-beta-D-galactopyranos ide as a key intermediate, which was in turn prepared by employing two glycosyl donors, 3,4-di-O-benzyl-2-deoxy-6-O-p methoxyphenyl-2-phthalimido-beta-D- glucopyranosyl trichloroacetimidate and O (3,6-di-O-acetyl-2,4-di-O-benzyl-beta-D-galactopyranosyl)-(1----4)-3-O - benzyl-2 deoxy-6-O-p-methoxyphenyl-2-phthalimido-beta-D-glucopyranosyl trichloroacetimidate, and a glycosyl acceptor, benzyl 2,4,6-tri-O-benzyl-beta-D galactopyranoside. PMID- 2208192 TI - Preparation of disaccharides having a beta-D-mannopyranosyl group from N phthaloyllactosamine derivatives by double or triple SN2 substitution. AB - Condensation of 1,2,3,4,6-penta-O-acetyl-beta-D-galactopyranose with methyl 3,6 di-O-benzyl-2-deoxy-2-phthalimido-beta-D-glucopyranoside, followed by alkaline methanolysis, gave a derivative of lactosamine that has an unsubstituted beta-D galactopyranosyl group. Tributyltin oxide-mediated allylation gave a good yield of the 3'-O-allyl (9) and a poor yield of the 3',6'-di-O-allyl ether (8). Protection of 9 at O-6' was achieved by reductive opening of the 4',6'-O anisylidene derivative, to give the 6'-O-(4-methoxybenzyl) ether 15. Conversion of 8 and 15 to their 2',4'-bis(trifluoromethanesulfonates), followed by SN2 reaction with benzoate, gave the corresponding beta-D-mannopyranosyl disaccharides. However, the model methyl 3-O-allyl-beta-D-galactopyranoside and 9 were converted into beta-D-mannopyranosyl derivatives in better yield (52-55%) by a one-pot, triple SN2 substitution of the tris(trifluoromethanesulfonates). PMID- 2208193 TI - Synthesis of a series of methyl beta-glycosides of (1----6)-beta-D-galacto oligosaccharides having one residue deoxygenated at position 3. AB - Methyl beta-glycosides of beta-(1----6)-linked D-galactobioses (13 and 16) and galactotrioses (21, 24, and 26) containing a 3-deoxy-beta-D-xylo-hexopyranosyl moiety either as one of the end units or the internal unit have been synthesized. The extension of the oligosaccharide chain was achieved, inter alia, by the use of two newly synthesized glycosyl donors derived from 3-deoxy-D-xylo hexopyranose, namely, 2,4,6-tri-O-benzoyl-3-deoxy-a-D-xylo-hexopyranosyl chloride (8) and 2,4-di-O-benzoyl-6-O-bromoacetyl-3-deoxy-a-D-xylo-hexopyranosyl chloride (10). Glycosylation reactions were mediated by silver triflate under base deficient conditions. PMID- 2208194 TI - Synthesis of stereospecifically labeled 3,6-dideoxyhexoses. AB - Preparations of ascarylose (3,6-dideoxy-L-arabino-hexose), abequose (3,6-dideoxy D-xylo-hexose), and paratose (3,6-dideoxy-D-ribo-hexose) with stereospecific deuterium labeling at C-3 are discussed. The methods used to synthesize these sugars, such as the hydrogenation of olefins, the displacement of halides, the reduction of epoxides, and the substitution of tosyl esters, illustrate a variety of strategies leading to stereospecific deuterium incorporation. Many of the techniques described here should be of general utility for the synthesis of other deuterium-labeled sugars. PMID- 2208195 TI - [Radioprotection in cardiology]. PMID- 2208196 TI - [Improvement in the accuracy of diagnosis of ischemic heart disease with simultaneous radioisotope evaluation of regional myocardial function perfusion and an exercise test]. AB - The recently developed myocardial agent methoxy-isobutyl-isonitrile (MIBI), labelled to 99mTc, allows one to evaluate global and regional ventricular function as well as myocardial perfusion by means of a single exercise stress test, significantly increasing diagnostic accuracy for coronary artery disease. Between September 1988 and March 1989, 407 patients with either suspected or already ascertained coronary artery disease underwent simultaneous assessment of regional ventricular function with first pass radionuclide angiography, and of myocardial perfusion with single photon emission computerized tomography, by means of 2 injections of 99mTc-MIBI at rest and at peak of the same exercise test. Out of these patients, 56 (52 men and 4 women, whose mean age was 57 +/- 7 years) underwent coronary angiography within 6 months of radionuclide examination and were included in the study. There were 13 1-vessel, 26 2-vessel and 17 3 vessel disease patients. Thirty-six of them had had a previous (greater than 6 months old) myocardial infarction, on the anterior wall in 16 patients, on the inferior wall in 20. In all patients a computerized bicycle stress test was performed; interruption criteria were ST segment depression greater than or equal to 1 mm in 27 patients (48%), the achievement of a heart rate greater than 85% of maximal age-predicted heart rate in 12 patients (22%) and fatigue in 17 patients (30%). Scintigraphic results were compared to angiographic findings: global sensitivity and specificity of the simultaneous evaluation were 82% and 81%, respectively, vs 95% and 56% of functional results and 85% and 71% of perfusion results, respectively. Regional analysis was also performed, by dividing scintigraphic images into the territories supplied by the 3 main coronary vessels, i.e., left anterior descending artery (LAD), left circumflex artery (LCx) and posterior descending artery (PD). On LAD territory the simultaneous evaluation achieved a sensitivity of 88% and a specificity of 63%, vs 98% and 38% of functional analysis and 88% and 50% of perfusional analysis, respectively. On LCx territory sensitivity and specificity were respectively 71% and 96%, vs 91% and 64% of function, and 77% and 96% of perfusion alone. On PD territory sensitivity was 85%, vs 94% and 91%, respectively; specificity was 73%, vs 55% and 55%, respectively. Combined functional and perfusional analysis achieved a 68% sensitivity in identifying less than or equal to 75% coronary narrowings, and a 90% sensitivity for greater than 90% narrowings.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2208197 TI - [ST segment depression in precordial leads in patients with inferior acute myocardial infarction: the role of right ventricular involvement]. AB - The aim of the present study was to evaluate the influence of right ventricular involvement on the magnitude of precordial ST segment depression during inferior acute myocardial infarction. For this reason 61 patients (55 M, 6 F; mean age 53 years--range 38-73 years) admitted in our CCU for inferior acute myocardial infarction were studied by coronary angiography within 3-5 days from the onset of symptoms. The angiography showed either occlusion or critical coronary stenosis ranging as follows: on right coronary artery proximal (Group 1) to the first branch for right ventricle in 22 patients, on right coronary artery distal to the first branch for right ventricle in 25 patients (Group 2) and on circumflex artery (Group 3) in 14 patients. No difference in LAD disease were noted between the 3 groups. Using myocardial scintigraphy (Tc-99m- pyrophosphate) we confirmed the presence or the absence of right ventricular involvement in the 3 groups. In the 3 groups the magnitude of ST segment depression in V2, selected as representative left-sided precordial lead, ranged as follows: Group 1: -0.25 +/- 1.34 mm; Group 2: -1.64 +/- 1.80 mm; Group 3: -2.00 +/- 1.97 mm. In patients with right ventricular involvement (Group 1) there was a statistically significant reduction of precordial ST segment depression either in comparison to Group 2 (p less than 0.01) or to Group 3 (p less than 0.005) but none between Group 3 and 2. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2208198 TI - [Doppler echocardiography in the functional evaluation of patients with pure mitral valve stenosis]. AB - To evaluate the utility of echo-Doppler (ED; PW, CW and color), 67 patients affected by pure mitral stenosis (20 M, 47 F, mean age 52 years) were submitted to ED examination. Right and left cardiac catheterization were performed in 20 patients within 24 hours before ED. Mitral area obtained by Doppler method (Hatle's formula) correlated highly with both echo-2 dimensional and hemodynamic area (r = 0.93, p less than 0.001; r = 0.95, p less than 0.001 respectively). It was possible to calculate systolic pulmonary pressure, in patients with tricuspid incompetence, (43.9 +/- 14.9 mmHg, range 25-80) which correlated significantly (r = 0.95, p less than 0.001) with hemodynamic data (40.2 +/- 12.7 mmHg, range 20 70). The left atrial-left ventricular pressure gradient was 15.6 +/- 6.9 mmHg, range 6-32; the mean pressure gradient was 8.4 +/- 3.7 mmHg, range 3-17; the pressure half time 170.2 +/- 62.3 ms, range 83-330. We observed different types of direction of transmitral jets: centrally directed (n = 34); forward antero lateral wall (n = 28); toward interventricular septum (n = 5). The transmitral jets presented 4 different appearances: scimitar-shaped (n = 28); candle flame (n = 24); mushroom (n = 9); double-jets (n = 6). No correlation was observed between the different types of transmitral jets (direction and appearance) and the parameters obtained by Doppler (PW and CW): velocities, pressure half-time, gradients. Thus, Doppler echocardiography permits a complete anatomic and functional evaluation of patients with pure mitral stenosis. We have not observed any correlation between the hemodynamic data and the different types of transmitral jets visualized by color Doppler. PMID- 2208199 TI - [Effects of chronic administration of nifedipine on echo-Doppler parameters of left ventricular filling in hypertensive patients]. AB - This study aimed determining the chronic effects of nifedipine (N) on left ventricular filling in 25 patients (mean age 55) with mild to moderate arterial hypertension. M-mode, B-mode and pulsed Doppler measurements were performed at baseline, after 30 min from administration of sublingual N (10 mg) and after 6 months of therapy with slow release N (max dose: 60 mg die). Acute and chronic N reduced significantly both systolic (p less than 0.001) and diastolic pressure (p less than 0.001). At the end of the treatment with slow release N, and septal wall thicknesses had a slight but significant decrease (p less than 0.01). Diastolic and systolic dimension were not modified. Left ventricular mass index decreased significantly from 141 +/- 34 to 130 +/- 31 g/m2 (p less than 0.05). The Doppler-derived diastolic filling indexes (peak E, ratio peak E/A,E deceleration) were abnormal at baseline, and had a significant increase after sublingual and chronic therapy. Changes in left ventricular mass index and diastolic filling indexes were not correlated. A significant correlation was found between peak E changes after acute and chronic N administration (r = 0.732 and p less than 0.001). The results of this study demonstrate that both acute and chronic administration of N modify transmitral flow velocity pattern, suggesting that, in hypertensive patients, left ventricular filling abnormalities are partly dynamic and reversible. Our findings also demonstrate that acute N effects may predict the chronic results. PMID- 2208200 TI - [Vector cardiography features of right ventricular activation delays: nosologic classification and clinical correlation]. AB - Electrovectorcardiographic features of 150 patients showing right ventricular activation delays (RVAD) has been analyzed. This analysis of RAVD, especially for type I, which is the group with the widest morphologic variability, has permitted a more detailed classification: a type I with 5 subtypes, a type II with 1 subtype, a type III and an intermediate type between type II and III. Fifty-five per cent of the patients were included in type I and its variant and most were classified, often without cardiac disease, as belonging to the classic type I. Thirty per cent of RVAD were of type II; 12% of type III and the remaining were in the intermediate group between type II and III. The various morphologies, moreover, were correlated with the clinical picture: the classic type I was never seen in subjects with cardiac disease, while the others types and subtypes were present either in subjects with cardiac disease or in elderly subjects, also without relevant pathologies (senile heart, especially, the type IA") or in otherwise healthy subjects. In a medical-social context, checking for RVAD, in the absence of cardiac disease, might usefully avoid further investigation. It is underlined the usefulness of this correlation for clinical prognostic judgement. PMID- 2208201 TI - [Determination of oxidative phenotype in a sample population and correlation with the pharmacokinetics of propafenone]. AB - Propafenone, like other cardioactive drugs (metoprolol, propranolol, encainide) is submitted to oxidative metabolism, evaluable by assessment of debrisoquine oxidative capacity. Two phenotypes have been described: extensive and poor oxidizers, with interethnic differences in the prevalence of poor oxidizers. Aims of this study were: 1) to assess the oxidative phenotype in a sample of the Italian population and 2) to evaluate the relationships between oxidative capacity and propafenone pharmacokinetics or pharmacodynamics. The ratio between debrisoquine (D) and 4-hydroxy-debrisoquine (4-OH-D) in the urines after D administration (10 mg) was employed to characterize oxidative phenotype in 90 subjects (42 arrhythmia patients and 48 healthy volunteers). In 10 patients, extensive oxidizers of debrisoquine, we studied propafenone (P) and 5-hydroxy propafenone (5-OH-P) kinetics after acute oral administration (450 mg) and chronic oral treatment (300 mg tid for 2 weeks), followed by wash out. RESULTS: 1) the prevalence of poor oxidizers (D/4-OH-D ratio greater than 12.6) in our population resulted to be 6.6%, like in other studies in Caucasians; 2) propafenone kinetics was strictly related to oxidative capacity since D/4-OH-D ratio strictly correlated with the ratio of P and 5-OH-P areas under curve in acute (r = 0.91) and in chronic administration (r = 0.90) and with P half-life in acute (r = 0.82) and in chronic administration (r = 0.82); 3) QRS widening both during chronic treatment and after acute administration correlated with oxidative capacity (r = -0.78 and -0.68 with D/4-OH-D ratio respectively) and with 5-OH-P areas under curve (r = 0.84 and 0.70 respectively); it did not correlate with P areas under curve. In conclusion both kinetics and electrophysiological effects of propafenone strictly correlate with oxidative capacity, even in extensive oxidizers. Thus even a small reduction in oxidative capacity may have relevant consequences during propafenone oral treatment. PMID- 2208202 TI - [Unusual anatomic coronary variants: parallel left anterior descending artery. Description of 3 cases]. AB - Three cases with a variation of the classic anatomic left anterior descending artery pattern, encountered unexpectedly during coronary arteriography, are reported. The importance of this unusual and rare coronary artery pattern is only anatomic, and the possibility to carry out these findings by the coronary arteriography, can increase their occurrence instead of an incidental finding. PMID- 2208203 TI - [Use of a balloon-tipped guidewire to pre-dilate coronary stenosis]. AB - Two cases of coronary angioplasty of very tight stenoses are reported in which, after failure of conventional low-profile catheters, a balloon-tipped guidewire was used to predilate the lesion, with subsequent advancement of a larger balloon catheter over the wire itself to complete the dilatation. It is suggested that this balloon-tipped guidewire can be helpful for safe predilatation of very tight coronary stenoses with no need for complex catheter exchanges. PMID- 2208204 TI - Effects of long term metoprolol administration on the electrocardiogram of rats infected with T cruzi. AB - STUDY OBJECTIVE: The aim of the study was to evaluate the role of beta receptor antagonists in the evolution of experimental Chagas' disease. DESIGN: Rats were infected with T cruzi, 2000 parasites.g-1 body weight, soon after weaning. One group was then given metoprolol, 100 mg.kg-1.d-1, in drinking water. A comparison group received no metoprolol. Two control groups of non-infected rats were also studied, one with and one without metoprolol in the same dose. SUBJECTS: Adult male albino rats were used: 144 were infected with T cruzi and received metoprolol (group IM), 137 were infected and received no metoprolol (group IW), 46 non-infected rats received metoprolol (group CM), and 43 non-infected rats did not receive metoprolol (group CW). MEASUREMENTS and main results--30 d after infection, resting ECG was performed in all surviving rats. (There were 63 deaths in the infected groups and none in the non-infected groups.) Abnormal ECG was found in 20/81 infected rats in group IM and in 30/74 in group IW (p less than 0.05). No ECG changes were found in the non-infected rats. Of rats in group IM with normal resting ECG, 31 continued to take metoprolol (group IMNM), while 30 similar rats did not (group IMNW); in group IM with abnormal ECG, 10 rats continued to take metoprolol (group IMAM), while 10 similar rats did not (group IMAW). Of rats in group IW with normal ECG, 22 were started on metoprolol (group IWNM), while 22 similar rats were not (group IWNW); in group IW with abnormal ECG, 15 rats were started on metoprolol (group IWAM), while 15 similar rats did not (group IWAW). After 120 d and 300 d infection there were no differences in mortality rate and Ajmaline test in any of the matched groups (IMNM X IMNW; IMAM X IMAW; IWNM X IWNW; IWAM X IWAW). After 120 d there was no difference in ECG between the groups, but after 300 d there was a decrease in abnormal ECG in group IWAM (IWAM v IWAW, 0/12 v 5/12, p less than 0.05). No histological differences were found. CONCLUSIONS: Metoprolol decreases the proportion of rats with abnormal resting ECG in both the acute and the chronic stage of T cruzi infection. PMID- 2208205 TI - Assessment of cellular viability in cardiovascular tissue as studied with 3Hproline and 3Hinulin. AB - STUDY OBJECTIVE: The aim of the study was to develop a quantifiable assay for the assessment of cellular viability in cardiovascular tissue. DESIGN: Radiolabelled proline and inulin were used to assess metabolic viability of the cellular component of cuspal tissue from porcine heart valves. EXPERIMENTAL MATERIALS: Pig hearts were removed within 20 min of death and transported on ice in tissue culture medium. Cuspal tissues were dissected rapidly and held on ice in physiological medium until assayed. MAIN RESULTS: Radiolabelled inulin was shown to be a useful marker for determining the amount of radiolabelled proline present in the extracellular tissue volume, permitting calculation of the amount of radiolabelled proline accumulated by the cellular component. Proline accumulation by the cellular component was affected by concentration of proline, time allowed for proline accumulation, in vitro cold ischaemia, and metabolic poisons. Based on mg tissue protein, proline and inulin accumulations were equivalent for aortic, pulmonary, mitral, and tricuspid valve tissues, suggesting that these valve tissues may be used interchangeably in assessment of metabolic viability of cellular components of cardiovascular tissue. CONCLUSION: Radiolabelled proline and inulin transport assays allow a quantitative estimate of total cellular viability. PMID- 2208206 TI - Endogenous adenosine enhances vagal negative chronotropic effect during hypoxia in the anaesthetised rabbit. AB - STUDY OBJECTIVE: Hypoxia potentiates the negative chronotropic effect of efferent vagal stimulation. A similar potentiation is evoked by exogenous adenosine. The aim of this study was to verify whether vagal potentiation during hypoxia is caused by endogenous adenosine. DESIGN: In anaesthetised rabbits the peripheral end of the right vagus was stimulated once every 20 s for 1 s, during normoxia and during systemic hypoxia, before and after adenosine receptor blockade. Hypoxia was induced by lowering oxygen content of the inspired air for 6 min. EXPERIMENTAL MATERIAL: 12 rabbits were anaesthetised with chloralose (50 mg.kg-1, intravenously) and halothane (0.3 vol%) and artificially ventilated. Reflex influences on heart rate were minimised by bilateral cervical vagotomy and administration of atenolol (1 mg.kg-1, followed by 0.25 mg.kg-1.h-1). Hypoxia was repeated before and after 8-phenyltheophylline administration (19.5 mumol.kg-1, intravenously) in seven rabbits, or before and after vehicle injection in five rabbits (time control). MEASUREMENTS AND RESULTS: The PaO2 attained at the end of the hypoxic period was 19(SEM 1) mm Hg [2.5(0.1) kPa]. Before adenosine receptor blockade, arterial pressure increased during hypoxia [14(6)mm Hg after 1 min], then decreased [7.3(8.8) mm Hg below control after 4 min]. Heart rate fell by 38.3(12.1) beats.min-1 in the last 3 min of hypoxia. Vagal negative chronotropic effect increased from -30.3(1.8) beats.min-1 during control to -58.7(4.6) beats.min-1 during the last 5 min of hypoxia, ie, a potentiation of 93.2(9)%. Administration of 8-phenyltheophylline reduced the effects of hypoxia on spontaneous heart rate and vagal bradycardia: heart rate decreased by 14.2(7.8) beats.min-1 and vagal negative chronotropic effect increased from -32.2(2.1) to 39.3(3.7) beats.min-1, ie, a potentiation of 21.5(10)%. Blood pressure showed a stronger increase [19.1(4.4) mm Hg after 2 min], but no decrease. These differences were not seen in the five control rabbits, in which hypoxia was repeated without adenosine receptor blockade. CONCLUSIONS: These results show that adenosine does play a role in hypoxia induced bradycardia and vagal potentiation. PMID- 2208207 TI - Reduced heart lipid peroxidation precedes cardiac dilatation in turkeys with naturally occurring cardiomyopathy. AB - STUDY OBJECTIVE: The aim of the study was to determine if reduced heart lipid peroxidation in 1-2 month old turkeys with furazolidone induced dilated cardiomyopathy is drug related and model dependent, a non-specific characteristic of the dilated turkey heart, or if alterations of heart lipid peroxidation can occur prior to onset of cardiac dilatation, and therefore may be involved in its pathogenesis. DESIGN: Ventricular lipid peroxidation capacity and superoxide dismutase activity were measured in controls and in turkeys with spontaneous cardiomyopathy at various ages (newly hatched, 7-10 d, and 1-2 months) and stages of the disease. SUBJECTS: 46 turkeys with naturally occurring dilated cardiomyopathy and 29 age matched controls were used at hatch, 7-10 d, and 1-2 months of age. MEASUREMENTS AND MAIN RESULTS: Heart lipid peroxidation, measured by thiobarbituric acid reactive substances (malondialdehyde), was found to be reduced not only in the dilated hearts of 1-2 months old cardiomyopathic turkeys [114(SEM 10) v 176(21) nmol.100 mg-1 protein, p = 0.023] but also in the non dilated hearts of 9-10 day old cardiomyopathic turkeys [135(17) v 274(35) nmol.100 mg-1 protein, p = 0.004]. Ventricular superoxide dismutase activity was similar in control and cardiomyopathic turkeys at all stages and there was the expected increase with age. In control turkeys ventricular superoxide dismutase activity in 1-2 month old birds, at 718(52) nitrite units.100 mg-1 protein, was significantly higher than values in 7-10 day old turkeys [398(31) nitrite units.100 mg-1 protein, p = 0.001]. CONCLUSIONS: Decreased lipid peroxidation capacity is present in the dilated hearts of spontaneously cardiomyopathic turkeys. However, it is also decreased in cardiomyopathic turkeys at 9-10 d (the time of highest mortality) prior to the onset of cardiac dilatation. Therefore, alterations in heart lipid composition may be involved in the pathogenesis of this cardiomyopathy and not simply a result of the cardiac dilatation/hypertrophy process. PMID- 2208208 TI - Isoenzyme profiles of creatine kinase, lactate dehydrogenase, and aspartate aminotransferase in the diabetic heart: comparison with hereditary and catecholamine cardiomyopathies. AB - STUDY OBJECTIVE: The aim was to investigate the redistribution of isoenzymes, clinically important markers of myocardial necrosis, in the diabetic heart and compare it with that investigated in other types of cardiomyopathies. DESIGN: Myocardial isoenzyme activity of creatine kinase (CK), lactate dehydrogenase (LD) and aspartate aminotransferase (AST) was measured in animals with diabetic, hereditary, and catecholamine cardiomyopathies. SUBJECTS: Diabetic rats (4 and 8 weeks after intravenous streptozotocin, n = 21), Bio 14.6 hamsters (30, 90, 160 and 240 days old, n = 29), and rats injected with isoprenaline (0.25, 0.5 and 1.0 mg.kg-1.d-1 for 3 weeks, n = 20) were used. Controls were age matched intact animals (n = 8-11). MEASUREMENTS AND MAIN RESULTS: Total CK and CK MM activity decreased in all groups. CK MB and BB decreased by 62 and 52% in diabetic rats, but increased by 40 and 33% in Bio hamsters and by 9 and 96% in isoprenaline treated rats. Thus the CK-B subunit decreased by 61% in diabetics and increased by 33 and 38% in Bio and isoprenaline groups, while the CK-M subunit decreased in all groups. Mitochondrial CK decreased in diabetic and isoprenaline groups. Total LD activity increased in diabetics and decreased in Bio. LD-H subunit increased by 21% in diabetics and decreased by 19 and 18% in Bio and isoprenaline groups. Accordingly the proportion of LD-M subunit, an index of anaerobic metabolism, decreased in diabetics and increased in Bio and isoprenaline groups. Changes in CK-M and CK-B subunits and the LD-M proportion in diabetic heart were normalised by insulin. Total AST activity decreased in diabetics because of the reduction in mitochondrial AST. CONCLUSIONS: Increased LD-M proportion and CK-B observed in Bio and isoprenaline groups may be a metabolic "compensation" to decreased myocardial perfusion and substrate. Decreased LD-M proportion and CK-B in the diabetic heart was insulin dependent and may indicate either lack of "compensation" to myocardial ischaemia or absence of ischaemia per se. Decreased myocardial CK and CK MB activity possibly causes underestimation of enzymatically assessed infarct size in the diabetic heart. PMID- 2208209 TI - Oxygen and extracellular fluid restriction in cultured heart cells: electron microscopy studies. AB - STUDY OBJECTIVE: To evaluate the effects of "simulated ischaemia" on the structure of cultured heart cells. DESIGN: Cultured heart cells were subjected for 2 h either to anoxia or to anoxia with simultaneous extracellular volume restriction ("simulated ischaemia"). Cells maintained under normoxic conditions served as controls. The cells were then fixed in situ in Petri dishes with formaldehyde-glutaraldehyde. EXPERIMENTAL MATERIALS: Heart cells from one day old rats on day 5 in culture were used. MEASUREMENTS AND RESULTS: Electron microscope studies were carried out on control and injured cells. "Mildly ischaemic" cells featured raffled and invaginated cell surfaces, reduced matrix density, disorientated mitochondrial cristae due to swelling, and giant mitochondria. Dilatation of rough endoplasmic reticulum and electron dense membrane bound vesicles were observed in the cytoplasm. CONCLUSIONS: The model of simulated ischaemia is in keeping with the classical picture of irreversible cell damage caused by ischaemic injury. PMID- 2208210 TI - Evaluation of transmitral pressure gradients at different heart rates: divergent action of isoprenaline and atropine. AB - STUDY OBJECTIVE: The aim was to record diastolic transmitral pressure gradients at high sensitivity to quantitate the effect on transmitral pressure gradients of changing the heart rate. DESIGN: Diastolic left atrial and left ventricular pressures were recorded at high sensitivity (40 mm Hg = 10 mm recorded deflection) in control conditions (heart rate 70 beats.min-1) and after intravenous administration of atropine or isoprenaline (heart rate 110 beats.min 1). A special ventricular extrasystole protocol enabled the zero level of the transmitral pressure gradients to be unequivocally determined at high heart rates. The effect of atropine and isoprenaline on the pressure gradients, absolute diastolic pressures, and diastolic time intervals was investigated. EXPERIMENTAL MATERIAL: 16 mongrel dogs, 16-25 kg, were used. MEASUREMENTS AND RESULTS: Below a heart rate of 110 beats.min-1, four distinct periods were identified, during which a pressure gradient existed. During early and late diastole, a positive pressure gradient was consistently followed by a negative pressure gradient. Mean negative pressure gradient during early diastole correlated with the pressure difference of rapid filling wave (r = 0.72, p less than 0.01) and with mean positive pressure gradient during early diastole (r = 0.66, p less than 0.01). At a heart rate of 110 beats.min-1, isoprenaline augmented, while atropine reduced, the mean positive pressure gradient during early diastole without affecting the time interval over which the gradient occurred. This divergent action of the two drugs was related to their different effects on the decay of left ventricular pressure, which fell faster and deeper with isoprenaline but not with atropine. Both drugs shortened the time interval of the negative pressure gradient in early diastole without significantly affecting the mean negative pressure gradient during this period. In late diastole, atropine augmented the mean positive pressure gradient more than isoprenaline, reflecting the higher afterload after administration of atropine. Neither drug affected the time interval of the positive pressure gradient. As a result of a shortening of the P-R interval, isoprenaline shortened the time interval of the negative pressure gradient and reduced its mean value. Such an effect was not observed with the dose of atropine used. CONCLUSIONS: We conclude that a pressure gradient reversal in early diastole is always observed below a heart rate of 110 beats.min-1 and that isoprenaline and atropine affect the pattern of transmitral pressure gradients in a different way. PMID- 2208211 TI - Expression of fibrillar types I and III and basement membrane collagen type IV genes in myocardium of tight skin mouse. AB - STUDY OBJECTIVE: The aim was to study the expression of fibrillar collagen types I and III and basement membrane type IV collagen in the heart of the tight skin mouse, a genetic mutant with collagen overproduction in various organs. DESIGN: Collagen gene expression was measured in the ventricular tissues of the heart of the tight skin mouse and the age matched homozygous (+/+) litter mates by the use of cDNA probes to alpha 2 (I), alpha 1 (III) and alpha 2 (IV) procollagen and northern and dot blot analysis. Collagen deposition was examined by immunofluorescent light microscopy using monospecific antibodies to types I, III and IV collagens. EXPERIMENTAL MATERIAL: Heterozygous male (TSK/+) and normal (+/+) mice, 1.5-2 months old of the C57BL/6 strain were used. The animals were anaesthetised and the hearts were rapidly excised and processed for RNA extraction and antibody staining. MEASUREMENTS AND RESULTS: The results of northern and dot blot analyses showed a 41% increase in mRNA level for collagen type I, a 63% increase in mRNA level for type III and a 33% increase in type IV collagen in the ventricular myocardium (right and left ventricles) of the tight skin mouse compared to its counterpart in age matched homozygous (+/+) litter mates. mRNA levels for beta actin showed no significant increase. Immunofluorescent light microscopy and monospecific antibodies to types I, III and IV collagens were used to examine collagen deposition. The results showed that collagen type I fibres are thicker and denser in perivascular areas of the tight skin mouse heart compared to normal heart. No abnormal accumulation of type III fibres was observed. CONCLUSIONS: The heart of the tight skin mouse may be an appropriate model for studying the up regulation of cardiac collagen gene expression and its potential contribution to myocardial diseases. PMID- 2208213 TI - [How urgent is the need to reform medical education?]. AB - Many proposals regarding reforms of our health services pertain to the organization, financing and material and technical equipment of health departments. But many people forget that the causes of inadequate meeting of health needs of individuals and society are much more profound. The present article draws attention to the urgent need of reforms of the medical curriculum at medical faculties and postgraduate institutes. The core of the problem are rigid forms of teaching and the absolute predominance of biomedical and technological aspects of training over psychosocial and sociooecological aspects of training of future doctors. The submitted paper refers to attitudes and recommendations of WHO and other international organizations concerned with medical training. PMID- 2208212 TI - Heterogeneity in cellular response and intracellular distribution of Ca2+ concentration during and after metabolic inhibition. AB - STUDY OBJECTIVE: To characterise cell injury during myocardial hypoxia and reoxygenation, [Ca2+]i was measured in guinea pig ventricular myocytes using digital images of fura-2 fluorescence. DESIGN: [Ca2+]i and cell morphology were measured during and after the perfusion of 2 mmol.litre-1 sodium cyanide (NaCN). EXPERIMENTAL MATERIAL: 28 ventricular myocytes isolated from guinea pig hearts. MEASUREMENTS AND MAIN RESULTS: Eight out of 28 cells became rounded during the perfusion with NaCN, and [Ca2+]i increased from 48 (SEM 6) nmol-litre-1 to 163(24) (p less than 0.01) before cell rounding, and to 311(46) (p less than 0.01) after cell rounding. Ten cells were rounded after the washout of NaCN, and [Ca2+]i increased to 252(41) nmol.litre-1 before cell rounding (p less than 0.01), and to 314(48) after cell rounding (p less than 0.01). Intracellular distribution of [Ca2+]i was heterogeneous in some cells with high [Ca2+]i. The values of [Ca2+]i before and after cell rounding, during and after the perfusion of NaCN, were significantly lower than those during the perfusion of strophanthidin (0.1 mmol.litre-1). CONCLUSIONS: There appeared to be a mixed population of myocytes, some showing normal [Ca2+]i and shape, and others showing high [Ca2+]i and contracture, during the perfusion or the washout of NaCN. Ca2+ overload alone is unlikely to be the main and the only mechanism of cell injury during myocardial hypoxia/reoxygenation. Other mechanisms such as membrane disturbance could be involved. PMID- 2208214 TI - [Lung infections after kidney transplantation. II. Diagnosis and therapy]. AB - In the diagnosis of pulmonary infections in patients after transplantations of the kidneys the main requirement is rapid assessment of the causal agent. This demand can be met only by collaboration of many specialists. Only when the diagnosis is established in time, the infectious process can be treated and the patient saved. An analysis of diagnostic and therapeutic procedures used in the examination of patients with pulmonary infections after transplantations of the kidneys is the subject of part II of the authors' paper. PMID- 2208215 TI - [Correlation of the autopsy with the clinical diagnosis in common neoplasms in a general hospital]. AB - The author correlated in a group of 1100 autopsies made in 1987-1989 the clinical and autoptic diagnosis of malignant neoplasms of the bronchi, lungs, stomach, large intestine and rectum, liver and extrahepatic biliary pathways, pancreas and kidneys. In the case of the stomach, large bowel, liver and pancreas the diagnosis moreover with the diagnosis of non-tumourous diseases of these organs. As compared with worldwide autoptic correlations, the diagnostic standard of carcinoma of the bronchi and lungs is roughly equal, in carcinoma of the liver it is better, in carcinoma of the extrahepatic biliary pathways and stomach it is worse. The diagnostic sensitivity of malignant tumours varies from 0.6 to 0.4 and thus in 40-60% of autoptic findings of the mentioned neoplasms an accurate clinical diagnosis was not established. The rate of diagnostic errors of the first type is, however, in this group of differing clinical and autoptic diagnoses lower than in diseases caused by infectious causal agents, the rate of errors of the second type is high. Comparison of the diagnosis of tumourous and non-tumourous diseases of the stomach, large bowel, pancreas and liver revealed roughly the same diagnostic standard with the exception of cirrhosis of the liver where it is lower. PMID- 2208216 TI - [The importance of comprehensive immunohematologic tests in paternity disputes]. AB - The authors describe four cases of paternity suits where the paternity was not ruled out according to HLA antigens and was ruled out in signs of erythrocyte, serum and enzyme systems, although the capacity of the HLA system was high, in two instances above 98%. From the results ensues that it is useful to supplement the examination by erythrocyte, serum and enzyme systems in those instances where HLA typing was performed first and the man was not ruled out. PMID- 2208217 TI - [The effect of social and biological factors on work disability in an industrial population]. AB - The authors analyze the influence of various factors on the work absenteeism in an industrial population. The work absenteeism changes significantly with age. Short, frequent incapacities, in particular on account of respiratory diseases, are typical for young age (approximately under 25 years). Least numbers of sickness days per year were recorded in workers in the fourth decade of life. Absenteeism on account of cardiovascular disease rises with age. The total work absenteeism is higher in manual workers, as compared with administrative workers and higher in women than in men. The differences depend also on the mean monthly income--the lowest rate of work absenteeism was recorded in people with a gross income above 4,500 Kcs. The influence of these factors in such that it is not possible to detect a relationship between work incapacity and biological factors, e.g. blood pressure, body weight, lipidogram, blood sugar level and others. It is beyond doubt, however, that the morbidity and mortality rate from non-infectious diseases depend on these factors. The causes of work incapacity are complex and are mostly influenced by circumstances beyond the health services. PMID- 2208219 TI - [The development of health insurance in Czechoslovakia]. PMID- 2208218 TI - [Rheumatic fever and rheumatic heart disease in the developing countries]. PMID- 2208220 TI - [Hygienic hospital arrangements for the care of patients with acute and chronic viral hepatitis B]. AB - The authors suggest a procedure for the treatment of patients with acute or chronic HBV infection (virus of hepatitis B) which did not lead--according to a special investigation of the hygiene service--to nosocomial infection. The results apply, however, only to the specially infection-oriented area of medical clinics, not to others such as e.g. dialyzation centres. There, due to generally known special features of the working regime and basic disease, it did not prove possible to prevent in all patients infection with the hepatitis B virus. PMID- 2208221 TI - [Visual loss and prejudice]. AB - Major or complete loss of eyesight is a serious interference with the activity and life of the affected subject. It is generally assumed that these subjects are quite helpless and that they suffer general deterioration. This is at variance with results of training and rehabilitation during which many thus affected subjects become independent, which is essential for their social integration. Despite this they have to experience sociopsychological attitudes which are prejudices with a typical stereotype which ignore the unique structure of everybody's potential who lost eyesight. The source of prejudices is general lack of information of people as regards actual sequelae of loss of eyesight and the emotional reaction of people with normal eyesight. A certain part is also played by tradition which does not take into account results of modern care of thus affected subjects. Prejudices cause in subjects with severely affected eyesight and in blind persons mental stress and render their actual social integration (employment, partnership etc.) more difficult. The solution is to train resistance against prejudices in thus affected subjects and to intensify health education on the given problem. PMID- 2208222 TI - [Anthropometric study of obese patients]. AB - The authors give an account of anthropometric examinations in obese patients. These methods are used not only for quantitative assessment of the degree of obesity but also to define the body fat distribution. The predominant body fat distribution in the upper body half on the chest and abdomen is typical for android obesity and is, contrary to gynoid obesity, a serious health risk as regards cardiovascular diseases and metabolic complications. The authors describe methods of assessment of body circumference and skinfolds. The degree of obesity is assessed from the body mass index (BMI) and the percentage of total body fat calculated from skinfolds measured by means of a caliper. The type of body fat distributions is usually expressed by the waist/hip ratio or by the ratio between the subscapular skinfold thickness and the skinfold above the tricept ("index of centralization"). Recently some authors advise to calculate by anthropometry also the amount of visceral fat which is a significant risk factor of cardiovascular and metabolic complications of obesity. PMID- 2208223 TI - Digital subtraction angiography in cerebrovascular diseases. Correlation of DSA with clinical findings. AB - Digital subtraction angiography (DSA) was performed in 100 patients with cerebrovascular diseases. The results of angiographic examination were compared with clinical findings on admission to and on discharge from hospital. The statistical evaluation was made on computers. Processing of anamnestic data revealed in the patients a large number of risk factors and other diseases, on average 3.68 per man and 3.96 per woman. 71% of the patients were examined on account of a relapse of some cerebrovascular disease. No relationship was found between the degree of the neurological deficit and clinical units on the angiographic finding. Clinically assumed arterial stenosis or occlusion was confirmed by DSA in 44.4%. On the other hand, in 57.9% of 38 affected subjects a stenotizing or obliterating process of the extracranial portion of the internal carotid was diagnosed in the absence of previous clinical suspicion. Of 76 patients with arteriosclerotic change in 56.6% the extracranial portion of the internal carotid was affected, incl. its bifurcation. Of 38 patients with stenosis or occlusion in 36.8% the affection was bilateral. Nine patients were indicated for operation, in another four endarterectomy of the internal carotid was done previously. DSA is a very useful examination method in patients with arteriosclerotic changes of the cerebral and cerebellar arteries. The risk for patients is, as compared with classical angiography, reduced while the obtained information on anatomical changes of the arterial wall is sufficient. PMID- 2208224 TI - [Serum levels and urinary excretion of zinc in patients with insulin-dependent diabetes]. AB - The objective of the work was to evaluate the basic parameters of zinc metabolism, i.e. serum levels and urinary excretion of zinc (Zn) in insulin dependent diabetes. The authors investigated a group of diabetics with normal renal function (DM) and with chronic renal insufficiency as a result of diabetic nephropathy (RIDM). Two control groups were formed by healthy volunteers (C) and non-diabetic subjects with chronic renal insufficiency (RI). In diabetics without impaired renal functions (DM) the Zn serum levels did not differ significantly from controls, urinary excretion was significantly raised. The authors did not reveal a correlation of serum Zn levels with parameters of compensation of diabetes nor with the insulin dose. Urinary Zn output correlated positively with proteinuria and the average blood sugar level during the collection of urine. The authors did not find a correlation with diuresis, fractional water excretion, glycosuria or urea excretion. The fractional Zn clearance in diabetic subjects was significantly raised and correlated with the mean blood sugar level. This finding suggests a decline of the tubular Zn absorption in hyperglycaemia. In diabetics with renal failure (RIDM) the results did not differ from non-diabetics with the same degree of renal insufficiency: serum Zn levels were, as compared with healthy controls, in both groups significantly reduced, the urinary excretion being normal. Thus insulin dependent diabetes nor its metabolic compensation do not influence in a marked way serum Zn levels but lead to higher urinary Zn losses.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2208225 TI - [Vitamin B1, B2 and B6 in erythrocytes in the nephrotic syndrome]. AB - In 19 patients with nephrotic syndrome in different diseases not associated with reduction of the glomerular filtration surface vitamin B1 was within the reference range, vitamin B2 was insignificantly and vitamin B6 significantly reduced. The concentrations of vitamins B1, B2 and B6 in red blood cells were assessed by indirect enzymatic methods and were expressed as vitamin action. Long term six-month riboflavin supplementation (2 mg/24 h) and pyridoxine (50 mg/24 h) in seven patients improved vitamin B2 and B6 levels in erythrocytes independently on the regression of the clinical and laboratory activity of the basic disease. PMID- 2208226 TI - [A rare case of paternity elimination based only on the HLA-C locus in the HLA system]. AB - The authors describe a rare paternity suit where paternity was ruled out in the HLA system only in locus HLA-C. The absence of HLA-Cw2 antigen on the lymphocytes was proved by the negative results confirmed by the same result on examination of the erythrocytes Ss system. PMID- 2208228 TI - [Occupational stress in health personnel and its prevention. Possible use of yoga]. AB - The paper summarizes some non-specific stress factors of work in the health services (e.g. shift work) and some relatively specific stressing factors (e.g. contact with grief, intense negative emotion and death). It deals also with the consequences of excessive stress, incl. the "burnout syndrome". It gives a brief account of possible preventive measures at the individual level and at the level of the organization. In the conclusion the author mentions the possibility to use yoga in the prevention of occupational stress in the health services. Work in the health services although, associated with considerable stress, is at the same time an opportunity for personality development and self-realization. PMID- 2208227 TI - [Pefloxacin in the treatment of recurrent urinary tract infections]. AB - Thirty-seven patients with relapsing infections of the urinary tract were treated with pefloxacine, 400 mg/12 h for a period of 7-28 days. The clinical success of treatment was 100%, the bacteriological success 95%. Within 3-4 weeks after termination of treatment 63% of the patients did not develop a relapse, in particular those who did not have morphological changes of the kidneys. Side effects-gastrointestinal, nervous, dermatological--during treatment were not severe. The results are comparable with results of the effect of ofloxacine in a similar group of patients. PMID- 2208229 TI - [Variation in heart rate after acute myocardial infarct]. AB - The reduced variability of the sinus rhythm is an adverse prognostic factor in patients after acute myocardial infarction. The paper is a review focused on the heart rate variability and its clinical correlate. The authors mention non cardiological areas where assessment of heart rate variability is done as a matter of convention or experimentally. Methods for assessment of heart rate variability are classified into three groups (spectral methods, statistical evaluation, evaluation of the distribution of RR intervals lengths) and each group of methods is briefly discussed. The authors quotes and comments work concerned with the prognostic impact of heart rate variability in post-infarction patients. The discussion is focused on problems which remain to be resolved before routine measurement of the heart rate variability in cardiological patients. PMID- 2208230 TI - [Correlation of the autopsy with the clinical diagnosis]. AB - Since Morgagni's times (1761) the purpose of autopsy is correlation of the clinical diagnosis and therapy, assessment of the cause of death, description and the diagnosis of unknown diseases, teaching and later collection of epidemiological data. The clinical and pathological correlation involves assessment of the sensitivity and specificity of the clinical diagnosis (autoptic findings are conceived as the reference value), and assessment of the frequency and seriousness of diagnostic errors. The importance of autopsies is apparent from the fact that the sensitivity and specificity of clinical diagnoses of some common diseases improved between 1930 and 1977, in others it remained the same, in others it deteriorated. Deterioration pertains in particular to the diagnosis of infectious diseases, some types of malignant tumours and diseases of the circulation, regardless of technological advances of diagnostic methods. The rate of errors in the diagnosis of basic diseases leading to death and immediate causes of death where knowledge of the autoptic diagnosis would probably changes the therapy and prognosis varies round 10%, the frequency of similar errors, where this knowledge would not alter the above procedures is twice or three times as high. If for the interpretation of autoptic results the "epidemiological" principle is used, the different incidence of common diseases in the population, as compared with official statistics becomes apparent, the official statistics being based on the collection of data from the death certificates. The latter data are biased by a high rate of diagnostic errors and selection phenomena. PMID- 2208232 TI - [Insufficient formation of interferon in children with recurrent respiratory infections]. AB - The authors investigated the ability of IFN-alpha formation in 50 children followed up on account of frequent and relapsing respiratory diseases. The ability to produce IFN-alpha was consistent with the clinical condition. Children who were frequently ill and whose condition did not improve during the last two years had an inadequate IFN-alpha production. Conversely, children whose health status improved substantially during the follow up period or those who were considered cured had a normal IFN-alpha production. Influencing of the IFN-alpha production might have a favourable effect on the clinical course of the disease. PMID- 2208231 TI - [Effectiveness of nifedipine, diltiazem and their combination in the treatment of chronic stable angina pectoris]. AB - In a double blind crossed ten-week study with a randomized beginning the authors compared in 25 patients with chronic stable angina pectoris (II-III according to NYHA classification) and with normal blood pressure the effect of placebo, nifedipine, diltiazem and in 16 of the patients (who completed treatment with the combined drugs) also a combination of nifedipine and diltiazem. Nifedipine, 60 mg per day, and diltiazem, 270 mg per day, improved significantly the total amount of performed work as compared with placebo, they delayed significantly the onset of stenocardias and reduced the ST depression in lead V5 during ergometry, they reduced significantly the rate of stenocardias per day as well as the nitroglycerin consumption. Diltiazem, as compared with nifedipine, increased significantly the total volume of performed work and delayed the development of stenocardias during ergometry, the symptomatic improvement of the patients being similar. A combination of 30 mg nifedipine per day with 180 mg diltiazem per day did not lead to improvement, as compared with a higher dose of diltiazem alone, as compared with a higher dose of diltiazem alone. A combination of 60 mg nifedipine per day with 270 mg diltiazem per day did not improve the exercise tolerance, as compared with diltiazem alone, however, it reduced significantly the rate of stenocardias. However, the combination of the latter amounts was tolerated without side-effects only by 13% of the patients (2 of 15 patients), 53% (8 of 15 patients) terminated treatment prematurely because of several side effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2208234 TI - [Selection of a compatible donor using the blood platelet aggregation technic]. AB - The authors assessed the test of platelet aggregation for the selection of a compatible donor. The test was compared with the hitherto used microlymphocytotoxic test. Consistent with data published abroad, the authors confirmed that the aggregation test improves the accuracy of selection of a suitable donor. The test can be performed in a shorter time than the microlymphocytotoxic test, this being important in particular in case of acute haemorrhage. PMID- 2208233 TI - [Elution of sensitized erythrocytes with chloroquine]. AB - The results of erythrocyte elutions sensitized either in vitro or in vivo with a 15% solution of Chloroquine indicate that at a low degree of sensitization it is possible in more than half of the tested cases to release incomplete antibodies from the red cell surface without causing damage of the group receptors. This makes it possible to assess the phenotypes of the majority of erythrocyte characteristics, although some may be weakened by elution. PMID- 2208235 TI - [Discussion of the article by K. Barinka, F. Broz, D. Nalos, M. Bakosova: Myasthenia gravis treated with plasmapheresis]. PMID- 2208236 TI - [Chromosome aberrations in workers in a printing press]. AB - Using cytogenetic analysis of peripheral lymphocytes the authors examined three groups of subjects: 42 rotogravure printers exposed to toluene in concentrations of 400-4400 mg.m-3 for a mean period of 13 years, 28 administrative employees of the printing plant exposed to low concentrations of toluene (8-16 mg.m-3) in their offices, whereby more than half of them spent on average two hours in the photogravure workshop, and 32 control subjects. In the printers 3.64% subjects, in the office staff 3.32% aberrant cells were found. The difference between the control group and the two groups from the printing plant was highly significant as regards the number of aberrant cells (P less than 0.005) and chromatid breaks and number of breaks per cell. The higher frequency of aberrant cells in probably associated with exposure to toluene, gravure printing dyes and in all three groups also with the highly contaminated communal atmosphere. PMID- 2208237 TI - [Factors affecting the incidence and severity of polyneuropathy in type I diabetes mellitus]. AB - 194 type I diabetics were subjected to neurological and electromyographic examinations. In 161 patients, i.e. in 83%, signs of polyneuropathy were detected, the severity of which was evaluated according to a 5-grade scale where grade 1 was the mildest and the 5th grade the most severe one. The authors proved a statistically significant correlation of the incidence and severity of polyneuropathy and the duration of diabetes. It was found that the decisive period of persistence of diabetes was 6-10 years. During this period the incidence of polyneuropathies increased from 30 to 87%. After 20 years duration of diabetes there was not only a 100% incidence of polyneuropathy, but severe affections--grade 3-5--predominated in 78%. In patients with severe grades of polyneuropathy diabetes was manifested at a significantly lower age than in patients without polyneuropathy and with a milder affection. The authors did not detect a significant relationship between the height of the patients and the incidence of polyneuropathy nor significant differences between men and women. PMID- 2208238 TI - [Mental retardation in children as a risk factor in pregnancy]. AB - The mentally retarded child is a risk factor of the subsequent pregnancy. This risk is usually not taken into account. Of 205 mothers with a mentally retarded child 95 became again pregnant. In 15 instances they gave birth to an affected child. During the preconception period almost one third did not attend any medical examination. With the problem of prenatal diagnosis interfere among others also socio-economic factors and sometimes also a low activity of health workers. PMID- 2208239 TI - [From the history of medical terminology. V. Lukas Schonlein and medical terminology]. PMID- 2208240 TI - [Audience with the Pope. John Paul II supports transplantation]. PMID- 2208241 TI - [Present problems of environmental contamination with so-called heavy metals]. AB - Till recently the true state and quality of the environment was kept secret. False pretension of a better state is one of the reasons not only for the poor state of our living environment but also for the poor health status of the population. The authors discuss the contemporary process of contamination and pollution of the environment as a result of economic activities and pays special attention to so-called heavy metals. PMID- 2208242 TI - [Comparison of the effectiveness of hemodialysis and hemofiltration in the removal of aluminum from the body]. AB - The authors compare the excretion of aluminium from the organism of patients with chronic renal failure during haemodialysis and haemofiltration. Aluminium can be eliminated from the organism only after previous administration of Desferal. Haemodialysis and haemofiltration alone practically do not eliminate aluminium from the organism. During haemodialysis made 24-40 hours after administration of 1 g Desferal (24 procedures, cuprophan plate dialyzer Chiraplat, urea clearance 2.5 ml/s, time 5 hours) the Al serum concentration declined by 41% and the dialyzer clearance for aluminium was during the 60th minute of haemodialysis 0.47 ml/s. During haemofiltration made 24-40 hours after administration of 1 g Desferal (36 procedures, polyamide haemofilter FH 77 on-line system of fluid exchange = 60% body weight) the Al serum concentration declined by 66% and the clearance of the haemofilter for Al was during the 60th minute 0.70 ml/s. Contrary to haemodialyzation treatment of Al intoxication, treatment with haemofiltrations was not associated with clinical complications. Haemofiltration treatment is a safe and effective method for the treatment of Al intoxication and accumulation in patients with chronic renal failure. PMID- 2208243 TI - [Pregnancy and labor in women with mitral valve prolapse]. AB - In a prospective study the authors investigated 30 pregnant women (mean age 27 +/ 5.5 years) with prolapse of the mitral valve confirmed on echocardiography, without significant mitral regurgitation, in order to assess whether mitral valve prolapse is a risk factor for the development of complications during gestation and childbirth. As control served a group of 30 healthy pregnant women of corresponding age and number of previous pregnancies, incidence of complications during pregnancy, the type of delivery, sex, length, weight and maturity of the neonates. In women with mitral valve prolapse the authors recorded a significantly higher incidence of subjective complaints such as palpitations associated in 7 of 8 cases with sinus tachycardia 110-140/min. at rest and with vasovagal syncopes. The palpitations were always favourably influenced by beta blocker therapy or by calcium antagonists. Mitral valve prolapse without haemodynamically significant mitral regurgitation during pregnancy is not a significant risk factor for the development of complications. PMID- 2208244 TI - [Trends in body weight in the population of the Czech Republic]. AB - The authors investigated the development of body weight of the population from six districts in the Czech Republic participating in the international WHO project MONICA. The examinations were made within the framework of epidemiological studies of risk factors of IHD in 1985 and 1988 in 1% independent population samples (range 25-64 years). The mean values of body mass index, BMI, increased in the above three-year period in men from 26.9 to 27.5 (p less than 0.001) in women from 26.9 to 27.4 (n. s.). The prevalence of obesity increased during the same period from 19.9% to 25.4% (p less than 0.001) in men and from 33.8% to 35.7% (n. s.) in women. In all decades of men and women there was a rising trend of body weight and increasing prevalence of obesity. With regard to the adverse effects of overweight on health and life span, the authors consider prevention of obesity as one of the foremost tasks of preventive medicine. PMID- 2208246 TI - [Visual function in patients with neuroretinopathy on regular dialysis treatment]. AB - Eight patients included in a regular dialyzation programme who developed neuroretinopathy were subjected to improved dialyzation treatment. It involved variation of sodium and variation of ultrafiltration. After regression of acute symptoms on the fundus in all patients a vision of 6/6 was achieved. Patients with neuroretinopathy have a markedly reduced contrast sensitivity. The latter increases considerably after absorption of the oedema, although it does not attain values recorded in healthy subjects. PMID- 2208245 TI - [Diagnosis of tuberous sclerosis using computer tomography]. AB - The authors examined 16 patients with tuberous sclerosis by computed tomography. In all patients calcifications were revealed, in the majority with a subependymal location, in 10 patients a medium severe hydrocephalus, in four a vaguely defined hypodensity, in two patients true tumours (astrocytomas). In six patients the clinical symptoms were atypical; in those instances computed tomography makes diagnosis of tuberous sclerosis possible. These findings are supplemented by data from the literature. PMID- 2208247 TI - [The blood group system in paternity disputes]. AB - The author presents a brief account of the literature on the secretory capacities of different antigenic systems on red blood cells, isoenzymes, serum proteins and the HLA system of leucocytes and provides information on his own experience when dealing with paternity suits. The certainty of elimination of men unjustly accused of paternity is high. PMID- 2208248 TI - [Quinolones in the treatment of bacterial endocarditis]. AB - The authors submit available information on the restricted use of new antimicrobial chemotherapeutic agents--quinolones--in the treatment of bacterial endocarditis in experiments and under clinical conditions. Quinolones are not suitable for the treatment of endocarditis except when the aetiological agent is Ps. aeruginosa, enterobacteria and in some instances endocarditis caused by meticillin-resistant staphylococci. The mentioned aetiological agents, however, cause endocarditis only in cca 5-10%. The results of experimental investigations on animal models as well as case-histories from human medicine are promising in this respect. PMID- 2208249 TI - Multi-Hospital Eastern Atlantic Restenosis Trial: design, recruitment, and feasibility. M-HEART Investigators. AB - A randomized control trial was set up to examine factors that influence restenosis and determine the effects of corticosteroids on restenosis following successful PTCA. The rationale for the study agent chosen, design, recruitment, and feasibility, as well as initial patient demographic data and initial results are presented. PMID- 2208251 TI - Klinefelter's syndrome with anomalous origin of left main coronary artery. AB - Klinefelter's syndrome is a rare entity. Even rarer is an anomalous origin of the Left Main Coronary Artery. For both conditions to occur in the same patient is hence exceedingly rare. Reported here is a never previously reported case of a coronary congenital anomaly in a patient with Klinefelter's syndrome together with the proper angiographic approach. PMID- 2208252 TI - Entrapment of a folded-over introducer sheath in the iliofemoral artery: an unusual complication of PTCA guiding catheter exchange. AB - An arterial introducer sheath became folded over in the iliac artery during PTCA. This probably resulted from withdrawal of a doubled over Judkins left coronary guiding catheter through the introducer sheath. Nonsurgical, atraumatic removal was accomplished after the acute bend of the introducer sheath had been withdrawn to the site of arterial entrance. PMID- 2208250 TI - Fractured and retained guide-wire fragment during coronary angioplasty- unforeseen late sequelae. AB - During a difficult coronary angioplasty, the tip of the guide wire became inadvertently wedged in a distal vessel, fractured, and retained in situ. Because of the otherwise successful nature of the angioplasty and the patient's great risk for cardiac surgery, it was elected to leave the wire fragment in place. Recurrence of symptoms led to recatheterization, which in addition to restenosis of the original angioplasty site showed diffuse narrowing of the arterial segment that contained the retained wire fragment. This occurred despite systemic anticoagulation with Coumadin in the interval between procedures. Thus retained guide wire fragments in patent coronary arteries may cause arterial narrowing despite systemic anticoagulation. PMID- 2208253 TI - An alternative method for transcatheter retrieval of intracoronary angioplasty equipment fragments. PMID- 2208254 TI - Use of the Arani Guiding Catheter with a twist. PMID- 2208255 TI - Angioplasty of small-diameter coronary arteries using an angiographic catheter and probe. PMID- 2208256 TI - Simplified method for estimating true aortic valve mean gradient from simultaneous left ventricular and peripheral arterial pressure recordings. AB - Estimation of the aortic valve gradient by simultaneous recording of left ventricular and peripheral arterial pressures is subject to error due to delay and modulation of the arterial pressure contour as it propagates from the ascending aorta. This error can be corrected by averaging the mean gradients derived from unaltered and temporally aligned simultaneous left ventricular peripheral arterial pressure tracings. In 26 patients with aortic stenosis and simultaneous recordings of ascending aortic and femoral arterial pressure we compared this method with a simplified approach in which the peripheral arterial pressure is partially aligned by advancing it against the left ventricular pressure by 50% of the time delay of the simultaneously recorded upstrokes. Gradients measured this way predicted the true aortic valve gradients (left ventricular-ascending aortic) with a mean difference of +1.1 mm Hg (range = +10 to -5 mm Hg). We recommend use of this simplified method of correction because it predicts true aortic valve gradient equally well as the averaging technique (r = 0.977 vs. 0.979) and requires half the time and effort. PMID- 2208257 TI - Experience with the use of coronary autoperfusion catheter during complicated angioplasty. AB - Between February and July of 1989, 22 patients underwent the use of the Stack autoperfusion catheter following acute occlusion or obstructive dissection during coronary angioplasty; in 20 cases conventional balloon was used in an attempt to correct the angiographic appearance followed by the use of Stack catheter when results were sub-optimal. Only 1 patient (4.5%) required surgical revascularization. Although our study is not prospective or randomized, our observations suggest a significant impact in decreasing the need for emergency surgical revascularization after complicated coronary angioplasty with the use of this approach. PMID- 2208258 TI - Ventricular fibrillation during coronary arteriography. PMID- 2208259 TI - Does percutaneous transluminal coronary angioplasty accelerate atherosclerotic lesions? AB - Recent reports have suggested that angioplasty may cause or accelerate coronary arterial stenoses secondary to traumatic injury. Ninety-four coronary angiograms performed in a 1 yr period were reviewed in patients who had successful coronary angioplasty 6 to 30 mo (mean 10.7) prior to restudy. Restenosis was found in 43 of 140 dilated lesions (31%) and in 41 of 94 patients (44%). Thirty-three (35%) patients had new or progressive lesions outside the angioplasty site. New or progressive lesions occurred with similar frequency in the arteries that did not have angioplasty (23/155 = 15%) as in the arteries that did (13/127 = 10%; chi square n.s.). In the arteries which underwent angioplasty, new or progressive lesions occurred as commonly proximal to the PTCA site (7/14, 50%) as distal (6/13, 46%). New or progressive lesions occurred in 29% of patients with concomitant restenosis, and 40% of those without restenosis (chi-square n.s.). No clinical, angiographic, or procedural factors distinguished patients with new and progressive lesions in target vessels from those without these lesions in target vessels. Patients with progressive lesions anywhere in the coronary tree were more likely to have had a shorter duration of anginal symptoms before angioplasty and a family history of coronary disease when compared with patients without progressive atherosclerosis. In conclusion, new and progressive lesions outside the angioplasty site occur after the procedure but appear unrelated to the restenosis process or traumatic injury by angioplasty instrumentation. PMID- 2208260 TI - Myocarditis simulating acute transmural myocardial infarction. AB - A patient with cardiogenic shock had typical electrocardiographic findings of acute anterior transmural myocardial infarction. Cardiac catheterization revealed normal coronary arteries and severe biventricular failure. Postmortem examination confirmed normal coronary arteries; acute myocarditis, but no evidence for infarction, was found. Electrocardiographic changes of myocarditis may be indistinguishable from acute transmural infarction. In suspected cases, cardiac catheterization should be considered prior to thrombolytic therapy. PMID- 2208261 TI - Misplacement of a Swan-Ganz catheter after insertion through the left internal jugular vein. AB - We report a case of perforation of the left brachiocephalic vein after insertion through the left internal jugular vein. Entrapment of air in the balloon occurred, possibly due to high surrounding tissue pressure at its base, preventing deflation. We emphasize the potential hazards of catheterization via the left internal jugular vein. PMID- 2208262 TI - Percutaneous valvuloplasty in a patient with mitral stenosis following surgical annuloplasty. AB - A case is described in which a patient with a Carpentier-Edwards annuloplasty ring developed mitral stenosis and was treated with percutaneous mitral valvuloplasty. Possible mechanisms for the development of mitral stenosis are briefly discussed. PMID- 2208263 TI - Salvage from cardiogenic shock by atherectomy after failed emergency coronary artery angioplasty. AB - In this case report of a patient undergoing angioplasty for cardiogenic shock during acute myocardial infarction, recurrent occlusion resulted in recurrence of shock. Atherectomy reestablished lasting patency and reversed the patient's hemodynamic collapse. Atherectomy deserves further investigation as a means to salvage vessel patency during unsuccessful coronary angioplasty. PMID- 2208264 TI - Left ventricular rupture complicating percutaneous mitral commissurotomy: salvage using percutaneous cardiopulmonary bypass support. AB - Left ventricular rupture resulting in death has been reported to be a complication of percutaneous mitral commissurotomy. We report a 71-year-old man in whom a left ventricular rupture occurred during percutaneous mitral commissurotomy and resulted in hemodynamic collapse due to acute cardiac tamponade. The patient was stabilized using percutaneously instituted cardiopulmonary bypass support with subsequent repair of the left ventricle and successful mitral valve replacement. Three months later this patient remains in New York Heart Class I. PMID- 2208265 TI - Coronary artery anomalies in 126,595 patients undergoing coronary arteriography. AB - Coronary artery anomalies were found in 1,686 patients (1.3% incidence) undergoing coronary arteriography at the Cleveland Clinic Foundation from 1960 to 1988. Of the 1,686 patients, 1,461 (87%) had anomalies of origin and distribution, and 225 (13%) had coronary artery fistulae. Most coronary anomalies did not result in signs, symptoms, or complications, and usually were discovered as incidental findings at the time of catheterization. Eighty-one percent were "benign" anomalies: 1) separate origin of the left anterior descending and circumflex from the left sinus of Valsalva; 2) ectopic origin of the circumflex from the right sinus of Valsalva; 3) ectopic coronary origin from the posterior sinus of Valsalva; 4) anomalous coronary origin from the ascending aorta; 5) absent circumflex; 6) intercoronary communications; and 7) small coronary artery fistulae. Other anomalies may be associated with potentially serious sequelae such as angina pectoris, myocardial infarction, syncope, cardiac arrhythmias, congestive heart failure, or sudden death. Potentially serious anomalies include: 1) ectopic coronary origin from the pulmonary artery; 2) ectopic coronary origin from the opposite aortic sinus; 3) single coronary artery; and 4) large coronary fistulae. Coronary artery anomalies require accurate recognition, and at times, surgical correction. PMID- 2208266 TI - Reciprocal ECG changes in acute myocardial infarction and angiographic correlation. PMID- 2208267 TI - Left main percutaneous transluminal coronary angioplasty with the autoperfusion catheter in an animal model. AB - Left main coronary angioplasty is associated with high risk because of interruption of blood flow to much of the left ventricle during balloon inflation. An "autoperfusion" balloon angioplasty catheter that allows blood to flow passively distal to an inflated balloon was tested in dogs and compared with inflations with standard balloon catheters. During 3 min occlusions of the left main coronary artery with the autoperfusion catheter, regional myocardial blood flow was preserved at 0.60 +/- 0.14 ml/min/g, compared with 0.07 +/- 0.03 ml/min/g during inflation with standard balloon catheters (P less than 0.01). Similarly, at the end of 3 min of inflation, left ventricular systolic pressure and dP/dt were maintained with autoperfusion catheter inflation, but they were severely depressed after standard angioplasty balloon inflation. All seven dogs survived autoperfusion balloon inflation, whereas five of seven developed sustained ventricular tachycardia and/or ventricular fibrillation during or after standard balloon inflation. Thus, distal blood flow, hemodynamics, and survival were preserved during autoperfusion balloon inflation in the left main coronary artery. PMID- 2208268 TI - A rapid, effective technique for retrograde crossing of valvular aortic stenosis using standard coronary catheters. AB - Retrograde crossing of valvular aortic stenosis can be challenging even to experienced angiographers. In 446 of 447 consecutive patients with aortic stenosis catheterized during the past 3 years, a technique using a standard Judkins right coronary catheter and a floppy straight tipped guide wire was successful in rapidly and efficiently crossing these pathologically distorted valves in retrograde fashion. Once the valve was crossed, the coronary catheter was replaced with a pigtail catheter for pressure and ventriculography. The majority of these valves required less than 2 min to cross using this technique. This method is valuable in limiting the time required for catheterization, thus helping to reduce procedure related morbidity in these oftimes critically ill patients. PMID- 2208269 TI - A new complication of coronary arteriography. AB - The introduction of a sharply angulated catheter through an arterial sheath for percutaneous coronary arteriography was associated in 7 cases with dissection of the iliac arteries; this extended to the lumbar aorta at the level of the coeliac axis. The catheter tip should be introduced gently and preferably straightened out with a good length of guide wire to avoid this complication. PMID- 2208270 TI - Interim standard: videotape recorders for transferring cardiac cinefluorographic studies. Laboratory Performance Standards Committee, the Society for Cardiac Angiography and Interventions. PMID- 2208271 TI - Transseptal left atrial catheterization. PMID- 2208272 TI - Acquired Lutembacher syndrome or mitral stenosis and acquired atrial septal defect after transseptal mitral valvuloplasty. AB - Critical mitral stenosis in selected patients may be treated successfully with percutaneous mitral valvuloplasty. Complications of this procedure, particularly an atrial septal defect following transseptal approach, are generally of minor clinical significance. We describe a woman who initially underwent a successful percutaneous double-balloon mitral valvuloplasty via the transseptal approach. Three months later she presented with right-sided heart failure. Color Doppler echocardiography and cardiac catheterization demonstrated an atrial septal defect (ASD) as well as restenosis of the mitral valve. We conclude that significant ASDs may occur following transseptal mitral valvuloplasty with appearance of right ventricular failure and that color Doppler imaging aids in the diagnosis of this new variant of the classical Lutembacher syndrome. PMID- 2208273 TI - Can the human genome project be saved from its critics ... and itself? PMID- 2208274 TI - Monomethylated cap structures facilitate RNA export from the nucleus. AB - RNA export from the nucleus has been analyzed in Xenopus oocytes. U1 snRNAs made by RNA polymerase II were exported into the cytoplasm, while U1 snRNAs synthesized by RNA polymerase III, and therefore with a different cap structure, remained in the nucleus. Export of the polymerase II-transcribed RNAs was inhibited by the cap analog m7GpppG. Spliced mRNAs carrying monomethylguanosine cap structures were rapidly exported, while hypermethylated cap structures delayed mRNA export. The export of a mutant precursor mRNA unable to form detectable splicing complexes was also significantly delayed by incorporation of a hypermethylated cap structure. The results suggest that the m7GpppN cap structure is likely to be a signal for RNA export from the nucleus. PMID- 2208275 TI - The integration host factor stimulates interaction of RNA polymerase with NIFA, the transcriptional activator for nitrogen fixation operons. AB - The regulatory protein NIFA activates transcription of nitrogen fixation (nif) operons by the sigma 54 holoenzyme form of RNA polymerase. NIFA from Klebsiella pneumoniae activates transcription from the nifH promoter in vitro; in addition, the integration host factor, IHF, binds between the nifH promoter and an upstream binding site for NIFA. We demonstrate here that IHF greatly stimulates NIFA mediated activation of nifH transcription in vitro and thus that the two factors are functionally synergistic. Electron micrographs indicate that IHF bends the DNA in the nifH promoter regulatory region. Although IHF binds close to the nifH promoter, it does not directly stimulate binding of sigma 54 holoenzyme. Rather, the IHF-induced bend may facilitate productive contacts between NIFA and sigma 54 holoenzyme that lead to the formation of open complexes. IHF binds to nif promoter regulatory regions from a variety of organisms within the phylum "purple bacteria," suggesting a general ability to stimulate NIFA-mediated activation of nif transcription. PMID- 2208276 TI - Structure and polymorphism of human telomere-associated DNA. AB - We have analyzed the DNA sequences associated with four different human telomeres. Two are members of distinct repeated sequence families which are located mainly but not exclusively at telomeres. Two are unique in the genome, one deriving from the long arm telomere of chromosome 7 and the other from the pseudoautosomal telomere. One telomere-associated repeated sequence has a polymorphic distribution among the chromosome ends, being present at a different combination of ends in different individuals. These data thus identify a new source of human genetic variation and indicate that the canonical features of the organization of telomere-associated DNA are widely conserved in evolution. PMID- 2208277 TI - A polybasic domain or palmitoylation is required in addition to the CAAX motif to localize p21ras to the plasma membrane. AB - The C-terminal CAAX motif of ras proteins undergoes a triplet of posttranslational modifications that are required for membrane association. The CAAX motif lies immediately C-terminal to the hypervariable domain, a region of 20 amino acids that distinguishes the ras proteins from each other. The hypervariable domains of p21H-ras, p21N-ras, and p21K-ras(A) contain sites for palmitoylation, which we now show must combine with the CAAX motif to target specific plasma membrane localization. Within the hypervariable domain of p21K ras(B), which is not palmitoylated, we have identified a novel plasma membrane targeting signal consisting of a polybasic domain that also acts in combination with the CAAX motif. One function of the hypervariable domains of p21ras is therefore to provide different signals for plasma membrane localization. PMID- 2208278 TI - Identification, purification, and biological characterization of hematopoietic stem cell factor from buffalo rat liver--conditioned medium. AB - We have identified a novel growth factor, stem cell factor (SCF), for primitive hematopoietic progenitors based on its activity on bone marrow cells derived from mice treated with 5-fluorouracil. The protein was isolated from the medium conditioned by Buffalo rat liver cells. It is heavily glycosylated, with both N linked and O-linked carbohydrate. Amino acid sequence following removal of N terminal pyroglutamate is presented. The protein has potent synergistic activities in semisolid bone marrow cultures in conjunction with colony stimulating factors. It is also a growth factor for mast cells. In two companion papers, we present the sequences of partial SCF cDNAs, identify SCF as a c-kit ligand, and map the SCF gene to the Sl locus of the mouse. PMID- 2208279 TI - Primary structure and functional expression of rat and human stem cell factor DNAs. AB - Partial cDNA and genomic clones of rat stem cell factor (SCF) have been isolated. Using probes based on the rat sequence, partial and full-length cDNA and genomic clones of human SCF have been isolated. Based on the primary structure of the 164 amino acid protein purified from BRL-3A cells, truncated forms of the rat and human proteins have been expressed in E. coli and mammalian cells and have been shown to possess biological activity. SCF is able to augment the proliferation of both myeloid and lymphoid hematopoietic progenitors in bone marrow cultures. SCF exhibits potent synergistic activities in conjunction with colony-stimulating factors, resulting in increased colony numbers and colony size. PMID- 2208280 TI - Activation and repression of myogenesis in somatic cell hybrids: evidence for trans-negative regulation of MyoD in primary fibroblasts. AB - We show that transfer of human fibroblast chromosome 11 (containing the human MyoD gene) from primary cells into 10T1/2 mouse fibroblasts by microcell fusion activates expression of the transferred human MyoD gene and converts these cells to myoblasts. Transfer of human chromosome 11 into B78 melanoma cells also leads to the activation of human MyoD. In contrast to the results where a single chromosome 11 is transferred, whole-cell hybrids between 10T1/2 cells and human skin fibroblasts do not express the myogenic phenotype; however, when specific human chromosomes are lost, myogenesis occurs. These results suggest that the MyoD locus is potentially functional in primary human fibroblasts, but is normally repressed in trans by a locus on a different human fibroblast chromosome. PMID- 2208281 TI - Molecular interactions within the ecdysone regulatory hierarchy: DNA binding properties of the Drosophila ecdysone-inducible E74A protein. AB - The E74 early ecdysone-inducible gene plays a key role in the regulatory hierarchy activated by ecdysone at the onset of Drosophila metamorphosis. We show here that E74A protein binds to three adjacent sites in the middle of the E74 gene. The consensus sequence for E74A protein binding, determined by random sequence oligonucleotide selection, contains an invariant purine-rich core sequence, C/AGGAA. This sequence is also present in the binding sites of two mammalian proteins that, like E74A, are related to the ets oncoprotein. Antibody staining of larval salivary gland polytene chromosomes revealed that E74A protein binds to both early and late ecdysone-inducible puffs. This study supports Ashburner's proposal that the early puffs encode site-specific DNA binding proteins that directly interact with the early and late ecdysone-inducible puffs. PMID- 2208282 TI - Steel locus defines new multipotent growth factor. PMID- 2208284 TI - TGF-beta stimulation and inhibition of cell proliferation: new mechanistic insights. PMID- 2208283 TI - Reduced DNA polytenization of a minichromosome region undergoing position-effect variegation in Drosophila. AB - Molecular analysis of a Drosophila minichromosome, Dp(1;f)1187, revealed a relationship between position-effect variegation and the copy number reductions of heterochromatic sequences that occur in polytene cells. Heterochromatin adjacent to a defined junction with euchromatin underpolytenized at least 60 fold. Lesser reductions were observed in euchromatic sequences up to 103 kb from the breakpoint. The copy number changes behaved in all respects like the expression of yellow, a gene located within the affected region. Both copy number and yellow expression displayed a cell-by-cell mosaic pattern of reduction, and adding a Y chromosome, a known suppressor of variegation, increased both substantially. We discuss the possibility that changes in replication alter copy number locally and also propose an alternative model of position-effect variegation based on the somatic elimination of heterochromatic sequences. PMID- 2208285 TI - A nonsecretable cell surface mutant of tumor necrosis factor (TNF) kills by cell to-cell contact. AB - In addition to the induction of tumor regression, tumor necrosis factor (TNF) has been implicated as the causative agent in a number of pathologies, including cachexia, septic shock, rheumatoid arthritis, autoimmunity, and induction of HIV expression. We propose that this complex physiology might be manifest by different forms of TNF: the 17 kd secretory component, the 26 kd transmembrane form, or both. To determine whether the 26 kd form of TNF was biologically active and whether its biology differed from that of the secretory component, we generated uncleavable and solely secretable mutants of TNF and studied their biological activities. We found that an uncleavable mutant of the 26 kd cell surface transmembrane form of TNF kills tumor cells and virus-infected cells by cell-to-cell contact, and that TNF need not be internalized by its target to kill. Thus, the 26 kd integral transmembrane form of TNF may function in vivo to kill tumor cells and other targets locally in contrast to the systemic bioactivity of the secretory component. PMID- 2208286 TI - The rate of bulk flow from the Golgi to the plasma membrane. AB - A truncated analog of the backbone of sphingomyelin and glycolipids was synthesized. This truncated C8C8 ceramide was soluble in water (but was still able to cross cell membranes) and was utilized by the Golgi apparatus of living cells to produce water-soluble truncated phospholipids and glycolipids that were then secreted into the medium. Sphingomyelin is synthesized in a proximal (likely the cis) Golgi compartment. At 37 degrees C in CHO cells, the sphingomyelin analog is secreted with a half time of about 10 min. With this rate of bulk flow, no special signal is needed to pass through the Golgi to the plasma membrane. At 30 degrees C the half time of secretion of a lumenal ER marker is about 18 min, and that of the truncated sphingomyelin is about 14 min. Comparison of these rates sets an upper limit of about 4 min for half of the ER to be drained into the proximal Golgi at 30 degrees C. PMID- 2208287 TI - Absence of the type I IFN system in EC cells: transcriptional activator (IRF-1) and repressor (IRF-2) genes are developmentally regulated. AB - Interferons (IFNs) are a heterogeneous family of cytokines that exhibits multiple biological activities. Upon viral infection, expression of type I IFNs (i.e., IFN alpha and IFN-beta) is induced in a variety of differentiated cells but not in cells of embryonal origin. IRF-1 and IRF-2, which bind to the same cis-elements within the promoters of type I IFN and IFN-inducible MHC class I genes, were identified previously. Here we demonstrate that the expression of both IRF and IFN genes is developmentally regulated in mouse EC cells; these genes become functional only after cell differentiation. Furthermore, cDNA-directed IRF-1 produced in undifferentiated but not differentiated EC cells efficiently activates the transfected IFN-alpha and IFN-beta and endogenous IFN-alpha genes, whereas IRF-2 represses the IRF-1 effects. These findings emphasize the dual function of the IRF-responsive cis-elements as positive and negative regulators, since they can be occupied by transcriptionally active or inactive IRF molecules. This type of regulatory mechanism might operate in other cytokine systems. PMID- 2208288 TI - The FT210 cell line is a mouse G2 phase mutant with a temperature-sensitive CDC2 gene product. AB - The mouse cell FT210 was isolated as a G2 phase mutant with a possible defect in the histone H1 kinase. We determined that a temperature-sensitive lesion in this cell line lies in the CDC2 gene. DNA sequence analysis revealed two point mutations in highly conserved regions of the gene: an isoleucine to valine change in the PSTAIR region, and a proline to serine change at the C-terminal region of the protein p34. These mutations cause the p34 protein kinase to become inactivated and degraded in FT210 cells at the restrictive temperature, 39 degrees C. The consequence of this temperature-induced inactivation of the CDC2 gene product is cell cycle arrest at the mid to late G2 phase, and this arrest can be alleviated by the introduction of the human CDC2 homolog. PMID- 2208289 TI - A novel protein binds a key origin sequence to block replication of an E. coli minichromosome. AB - A sequence of three tandem repeats of a 13-mer in the replication origin (oriC) of E. coli is the highly conserved site of opening of the duplex for initiation of DNA synthesis. A protein that binds this sequence has been discovered in E. coli and purified to homogeneity. This novel 33 kd polypeptide behaves as a dimer. Binding to the 13-mers is specific and limited to this region. At a ratio of 10-20 monomers per oriC plasmid, the binding blocks initiation by preventing the opening of the 13-mer region by dnaA protein. Once the 13-mers are opened by dnaA protein action, the 33 kd protein is without effect on the subsequent stages of replication. The specificity of binding and profound inhibitory effect suggest a regulatory role for this protein at an early stage of chromosome initiation. PMID- 2208290 TI - Extrathymic selection of TCR gamma delta + T cells by class II major histocompatibility complex molecules. AB - The influence of MHC antigens on TCR gamma delta usage in CD8+ intraepithelial lymphocytes (IELs) was examined using a pan-reactive and V delta 4 region specific MAb. While an average of 30% of IELs from the majority of mice of various MHC haplotypes were V delta 4+, a 2-fold or greater percentage of IELs from H-2k mice were V delta 4+. Analysis of IELs from F1 mice indicated that the increase in TCRs using V delta 4 was likely to be the result of positive selection. The V delta 4 usage patterns of IELs from recombinant inbred strains and from mice recombinant within H-2 revealed that the increase in V delta 4 usage mapped to H-2 and required I-E expression. Moreover, selection of TCRs using V delta 4 occurred in chimeric mice in the absence of a thymus. The results demonstrate an extrathymic selective mechanism for gamma delta TCRs of CD8+ IELs and suggest that these cells may exhibit MHC class II-restricted antigen recognition. PMID- 2208291 TI - Complete replication of a eukaryotic virus RNA in vitro by a purified RNA dependent RNA polymerase. AB - A soluble RNA-dependent RNA polymerase was isolated from Nicotiana tabacum plants infected with cucumber mosaic virus (CMV), which has a genome of three positive strand RNA components, 1, 2, and 3. The purified polymerase contained two virus encoded polypeptides and one host polypeptide. Polymerase activity was completely dependent on addition of CMV RNA as template, and the products of reaction were single-stranded (ss) RNA and double-stranded (ds) RNA, corresponding to RNAs 1, 2, and 3, and a subgenomic RNA (RNA 4) derived from RNA 3. The ratio of ssRNA to dsRNA was about 5:1, and the ssRNA was shown to be predominantly the positive strand. This demonstrates the complete replication of a eukaryotic virus RNA in vitro by a template-dependent RNA polymerase. PMID- 2208292 TI - Differentiation of canalicular cell processes in bone cells by basement membrane matrix components: regulation by discrete domains of laminin. AB - We have investigated the interaction of rat primary calvarial bone cells and a mouse osteoblast-like cell line MC3T3-E1 with basement membrane components. On a reconstituted gel of basement membrane, both cell types attached and formed isolated clusters that developed long interconnecting cell processes similar to the canalicular network observed in bone. The differentiation of the osteoblastic phenotype was stimulated as determined by increased alkaline phosphatase production and the deposition of mineral. Antibodies to laminin and to a 32/67 kd laminin receptor blocked this differentiation. Cell morphology was altered by the addition of active laminin-derived synthetic peptides, YIGSR-NH2 and CSRARKQAASIKVAVSADR-NH2, but not by an active RGD-containing peptide. When coated directly on plastic, all three peptides promoted cell adhesion, demonstrating that bone cells interact with specific molecular domains of laminin. These data demonstrate that basement membrane plays a key role in formation of a network of cytoplasmic processes resembling the osteocyte canalicular network in bone. PMID- 2208294 TI - Amy remembered. PMID- 2208293 TI - Rubber dam hazards. AB - Though repeatedly proclaimed as an indispensable element of quality operative dentistry, the rubber dam is seldom used in private practice. This is because of numerous hazards and inconveniences for the patient and dentist which have been rarely mentioned. These dangers and more effective alternatives to the dam's use in modern dentistry are discussed. PMID- 2208295 TI - Role models to remember. PMID- 2208297 TI - Research in private practice. PMID- 2208296 TI - Drugs and dentistry problem? What problem? PMID- 2208298 TI - A century of service. PMID- 2208299 TI - Student clinicians: the tradition continues. PMID- 2208300 TI - Characterization of cell-surface receptors for monoclonal-nonspecific suppressor factor (MNSF). AB - Monoclonal-nonspecific suppressor factor (MNSF) is a lymphokine derived from murine T cell hybridoma. The target tissues are both LPS-stimulated B cells and Con A-stimulated T cells. Since the action of MNSF may be mediated by its binding to specific cell surface receptors, we characterized the mode of this binding. The purified MNSF was labeled with 125I, using the Bolton-Hunter reagent. The labeled MNSF bound specifically to a single class of receptor (300 receptors per cell) on mitogen-stimulated murine B cells or T cells with an affinity of 16 pM at 24 degrees C, in the presence of sodium azide. Competitive experiments showed that MNSF bound to the specific receptor and that the binding was not shared with IL2, IFN-gamma, and TNF. Various cell types were surveyed for the capacity to specifically bind 125I-MNSF. 125I-MNSF bound to MOPC-31C (a murine plasmacytoma line) and to EL4 (a murine T lymphoma line). The presence of specific binding correlates with the capacity of the cells to respond to MNSF. These data support the view that like other polypeptide hormones, the action of MNSF is mediated by specific cell surface membrane receptor protein. Identification of these receptors will provide insight into the apparently diverse activities of MNSF. PMID- 2208301 TI - Interleukin 6 is essential for antibody secretion by human in vivo antigen induced lymphoblastoid B cells. AB - In vivo immunization of normal subjects with a variety of antigens generates circulating lymphoblastoid (LB) B cells, which in vitro spontaneously secrete significant levels of specific antibody. Since activation and initial differentiation of these cells occurs in vivo, they provide a useful model for the study of the later stages of B cell maturation. In the present study, we investigated the requirement of interleukin 6 (IL-6) for the "spontaneous" in vitro production of IgG-Tet by LB B cells. Addition of IL-6 to cultures of LB B cells in medium supplemented with 10% fetal calf serum failed to increase the levels of IgG-Tet produced in vitro. However, addition of anti-IL-6 antibodies decreased IgG-Tet production as much as 70%, and this inhibition could be reversed by the addition of IL-6. LB B cells cultured in serum-free medium in order to restrict endogenous IL-6 production secreted only low levels of antibody, unless exogenous IL-6 was added. Addition of 2.5 units/ml of IL-6 to serum-free cultures induced an increase in IgG-Tet secretion nearly comparable to that seen in cultures supplied with serum. The magnitude of the increase in IgG Tet secretion in response to exogenous IL-6 was inversely related to the number of cells in culture, which was due in part to increased endogenous IL-6 production in cultures with higher cell concentrations. Experiments including hydroxyurea in serum-free cultures indicated that IL-6-dependent enhancement of LB B cells' IgG-Tet secretion was not primarily mediated by cell growth. These observations suggest that in vivo generated LB B cells are not totally committed to antibody secretion, and that IL-6 is essential for in vivo antigen-induced LB B cells to reach the antibody-secreting stage. PMID- 2208302 TI - The expression of granulocyte/macrophage colony-stimulating factor in activated mouse lymphocytes declines with age. AB - The expression of granulocyte/macrophage colony-stimulating factor (GM-CSF) was studied in spleen lymphocytes isolated from male C57BL/6J mice of 6, 20, and 29 months of age. GM-CSF expression (biological activity and mRNA level) was maximum after culturing the lymphocytes for 45 hr with concanavalin A and phorbol myristate acetate. The induction of both GM-CSF activity and mRNA levels was observed to decline over 60% between 6 and 29 months of age. The age-related decline in the level of GM-CSF paralleled the age-related decline in the mRNA levels of interleukin-2 and interleukin-3. PMID- 2208303 TI - Phylogeny of immune recognition: antigen processing/presentation in channel catfish immune responses to hemocyanins. AB - Studies were conducted to address the role(s) of antigen (Ag) processing/presentation in channel catfish immune responses. Vigorous and specific secondary in vitro proliferative and antibody (Ab) responses were obtained to keyhole limpet and Limulus polyphemus hemocyanins with peripheral blood leukocytes (PBL) from catfish previously primed in vivo with Ag. In addition, such antigen-specific in vitro proliferative and Ab responses were efficiently elicited by antigen-pulsed and subsequently paraformaldehyde-fixed autologous PBL used as putative antigen-presenting cells (APC) but not by APC fixed prior to Ag pulsing. Treatment of these putative APC with lysosomotropic agents, protease inhibitors, or the ionophore monensin prior to or during pulsing with Ag significantly inhibited both in vitro responses. Furthermore, the use of radiolabeled protein indicated that both untreated and inhibitor-treated PBL but not erythrocytes take up Ag; however, only untreated PBL were able to degrade Ag. Immune restriction was indicated by the use of allogeneic PBL as APC in that only strong MLRs were generated with no detectable antibodies produced in vitro. Finally, the employment of isolated leukocyte subpopulations demonstrated that both catfish B (sIg+) lymphocytes and monocytes were efficient Ag presentors. PMID- 2208305 TI - PAF metabolism in resident and activated alveolar macrophages: role of protein kinase C. AB - Platelet-activating factor (PAF) metabolism was studied in resident and activated alveolar macrophages. Macrophages were obtained from normal Sprague-Dawley rats and from rats previously injected with complete Freund's adjuvant. Macrophages were attached and stimulated for 90 min. Then, cell PAF was extracted and quantitated by thin-layer chromatography. We found that in both resident and activated macrophages, calcium ionophore A23187 was a potent stimulus for PAF production while phorbol myristate acetate (PMA) was not. PMA and ionophore acted synergistically to increase PAF content in resident macrophages. This synergism was not observed in activated macrophages. To examine if this difference between resident and activated macrophages was due to a difference in PAF degradation, we assayed acetylhydrolase, the PAF-degrading enzyme. We found that ionophore stimulated acetylhydrolase activity in activated macrophages, but not in resident macrophages. Furthermore, PMA potentiated the ionophore effect in activated macrophages. This synergism was less obvious in resident cells. We conclude that PAF metabolism is different in activated and resident alveolar macrophages. Protein kinase C may play an important role in acetylhydrolase regulation in these cells. PMID- 2208304 TI - The proliferative response of rat T cells to calcium ionophores increases with age. AB - Splenocytes and T cells from both old and young rats proliferate to A23187 and ionomycin, and this response increases 3- to 10-fold in aged animals. Augmented responsiveness to ionomycin occurs in the absence of any defect in Con A-induced proliferation of T lymphocytes of aged rats and is dependent upon the addition of thiol compounds to the tissue culture medium. Augmented proliferative responses to ionomycin precede the significant but much smaller decline (30 to 40%) in Con A-induced proliferative responsiveness of splenocytes, which is evident only when rats reach 24 months of age. Heightened proliferation to calcium ionophores is not caused by a greater ability of T lymphocytes from aged rats to increase [Ca2+]i in response to ionomycin. The increased proliferative response of lymphocytes from aged rats to ionomycin occurs in the absence of detectable amounts of secreted IL 2 or IL 4. The ionophore response is a much more sensitive biomarker of age than the decline in Con A-induced proliferative responses of lymphocytes and identifies an activity of T lymphocytes that increases rather than decreases during the aging process. PMID- 2208306 TI - Distinctive features in the production of IL-6 by human T cells. AB - The production of IL-6 was studied in purified populations of human peripheral blood T cells and monocytes. IL-6 could be elicited from both T cells and thymocytes by a variety of polyclonal stimuli. The expression and production of IL-6 in T cells varied in several ways from that of monocytes: (1) under maximal stimulation, T cells secreted 10-fold less IL-6 than did monocytes; (2) by Western blot, the molecular isoforms produced by T cells were distinct from those produced by monocytes, with at least some isoforms being unique to each cell type; (3) the kinetics of IL-6 expression and production was much slower in T cells than in monocytes; (4) the frequency of labeled cells detected by in situ hybridization was 4% for T cells and 34% for monocytes. Our data indicate that there is considerable diversification among cell types in terms of regulation of IL-6 production and possibly in post-translational modifications. This raises the possibility that the IL-6 produced by different cell types may have varying effects depending on the form produced and the timing of synthesis. PMID- 2208308 TI - Interleukin-2 mRNA expression, lymphokine production and DNA synthesis in glutathione-depleted T cells. AB - The stimulation of DNA synthesis in lymphocyte populations was previously shown to depend strongly on the intracellular glutathione (GSH) level. Since T cell growth is known to depend on interleukin 2 (IL-2), the experiments in this report were designed to determine whether intracellular GSH depletion may inhibit IL-2 production or the IL-2 dependent DNA synthesis. Our experiments revealed that IL 2 production and DNA synthesis of mitogenically stimulated splenic T cells have indeed different requirements for GSH. The addition of relatively high concentrations of GSH (5 mM) to cultures of concanavalin A (Con A)-stimulated splenic T cells was found to augment strongly the DNA synthesis but inhibited the production of IL-2. Moderate intracellular GSH levels, however, are apparently not inhibitory for IL-2 production, since intracellular GSH depletion by cysteine starvation or by graded concentrations of DL-buthionine sulfoximine (BSO) had virtually no effect on IL-2-specific mRNA expression and the production of T cell growth factor (TCGF). The DNA synthesis activity, in contrast, was strongly suppressed after GSH depletion with either method. As in cultures of splenic T cells, GSH depletion had no substantial effect on the induction of IL-2 mRNA and TCGF production in several mitogenically stimulated T cell clones. Taken together, our experiments suggest that complex immune response may operate best at intermediate GSH levels that are not too high to inhibit IL-2 production but sufficient to support DNA synthesis. PMID- 2208309 TI - [A new topical preparation for the treatment of burns. I. Technical aspects of preparation]. AB - In the present paper some problems connected with the formulation of a topical preparation of the hydro-ointment type intended for the treatment of deep dermal burns were examined. Sixteen ointment bases containing hydroxypropyl methylcellulose, hydroxyethylcellulose, Carbopol 934 and Pluronic F-127 as gel forming substances were evaluated. The local anaesthetic agents carbizocaine and lidocaine served as active ingredients. Suitability of ointment bases was evaluated on the basis of their liberating capability for drugs, rheological properties and washability. The results show that an increase in the concentration of the gel-forming substance in the ointment resulted in a decrease in carbizocaine liberation. A decrease in the released amount of drugs occurred also after an addition of a humectant additive to the ointment base. The local anaesthetic agents under study decreased the viscosity of ointment bases. The highest coefficient of washability was found in the Carbopol ointment base. From the viewpoint of administration, the base with 1% Carbopol, or a combined base with 2% Methocel and 0.5% Carbopol proved to be most suitable. PMID- 2208307 TI - Granulocyte-macrophage colony-stimulating factor enhances macrophage accessory function in con A-stimulated T-cell proliferation. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been reported to augment various macrophage (M phi) functions, including antigen presentation in the antibody-producing response. We investigated the augmentative effect of GM CSF on M phi A-cell activity in concanavalin A-stimulated T-cell proliferation. Pretreatment with GM-CSF of peritoneal M phi enhanced the T-cell proliferative response. This effect of GM-CSF was dose dependent and GM-CSF supplementation was needed at the beginning of M phi culture. We observed that GM-CSF induced M phi spreading and firm attachment accompanied with enlargement of the cytoplasm, but could not induce de novo expression of Ia antigen. GM-CSF treatment enabled M phi to produce more interleukin (IL)-1 and IL-6 upon stimulation with lipopolysaccharides or polyinosinic-polycytidylic acid, but was unable to stimulate M phi directly. This was confirmed by Northern blot analysis. These results indicate that GM-CSF augments M phi A-cell activity through the enhancement of the capacity of M phi to produce IL-1 and IL-6. PMID- 2208310 TI - [Interaction of tobramycin and its derivatives with mitochondria in vitro]. AB - Tobramycin modified with fluorescamin yields fluorescent derivatives with a gradually changed structure and charge composition. Interactions of these drugs with mitochondria were investigated on the basis of the measurement of their inhibitory effect on the respiration (consumption of O2) of the isolated mitochondria. The results were compared with the effects of the original antibiotic agent. The use of the method of fluorescence polarization made it possible to determine the character of interactions. The procedure is a model experiment with possible wider use. PMID- 2208311 TI - [Evaluation of the suitability of labor induction using the oxytocin stress test]. AB - The authors elaborated an oxytocin loading test with a continual increase of oxytocin, which was used not with regard to the antepartal threat to the foetus but at the same time also for assessing whether induction of labour is advisable. This criterion was not mentioned in the literature so far. For evaluation of the sensitivity of the uterus the mutual association of the index of the uterine cervix, the number of days before childbirth and the necessary dose of oxytocin was used. If the required three contractions developed within the time interval of 10 mins. after the smallest oxytocin dose, the sensitivity of the uterine muscle was evaluated as good, after the double dose as medium, after the largest dose of oxytocin as weak sensitivity. The results of the thus arranged oxytocin loading test are above the borderline of the screening test and pass into the zone of a diagnostic method. To verify this important fact it is necessary to test according to epidemiological criteria the results attained in this so-called "preliminary" group in a more extensive "test" group. PMID- 2208313 TI - [Use of the ELISA test for the determination of sperm antibodies in the serum and follicular fluid in sterile women]. PMID- 2208312 TI - [A new method of evaluating the oxytocin stress test]. PMID- 2208315 TI - [Urodynamic examination of patients after irradiation for gynecologic carcinoma]. PMID- 2208314 TI - [Treatment of stress incontinence using the tricyclic antidepressive agent imipramine (Melipramin)]. PMID- 2208316 TI - [Results of surgical treatment of the polycystic ovary syndrome]. PMID- 2208317 TI - [Endometrial carcinoma in young women]. PMID- 2208318 TI - [Risks in the administration of glucocorticoids in pregnancy]. PMID- 2208319 TI - [Tocolysis]. PMID- 2208320 TI - [Possibilities of hormonal treatment of endometrial carcinoma]. PMID- 2208321 TI - [Cui prodest? Comments on the report by K. Vizek, P. Cepicky. T. Lomickova "Is breast feeding and nutrition with mother's milk always optimal?" Cs. Gynekologie, 54, 1988, no. 6, p. 469-472]. PMID- 2208322 TI - [Drug prescriptions in ambulatory facilities]. PMID- 2208323 TI - [Where are we failing in gynecologic-obstetrical psychosomatic medicine? Selection of reports presented at the national meeting of the Commission for Psychosomatic Medicine in Gynecology and Obstetrics in Prague, 18 October 1989]. PMID- 2208324 TI - [Myelodysplastic syndromes]. AB - Myelodysplastic syndromes (MDS) are a group of heterogenous disorders of blood and of the haematopoeitic bone marrow which have been recently in the center of interest of both clinical haematologists and pathologists. The FAB classification is based on cytology; for histological assessment, a special histopathological classification appears to be more appropriate. The main histological findings in MDS and some ultrastructural changes are shown in 138 bone marrow biopsies from 81 patients with MDS. Histological examination brings some findings that cannot be obtained by cytology. Optimal samples well processed can give valuable information without need of special staining methods. The latter can complement the basic information with some additional data or compensate for some technical defects of the slides. PMID- 2208325 TI - [Anaplastic osteoclastic carcinoma of the gallbladder]. AB - Description of an unusual carcinoma of the gall bladder in a 55 year-old woman. Bioptical finding based on light microscopy, electron microscopy and immunohistology is compared with autopsy. Histogenesis of osteoclast-like structures in the carcinoma is discussed. PMID- 2208326 TI - [Sputum and the detection of pulmonary carcinoma]. AB - During 1984-1988, 16,779 sputa from 3546 patients were studied. Minimal requirements of representability were obtained in sputa of 2500 (70.5 per cent) patients under study. Total of unsatisfactory samples reached 4812 (28.7 per cent). Even sufficiently repeated taking of sputum failed to produce any representable material from 267 patients (7.5 per cent). Carcinoma was identified in 455 cases (18.2 per cent), cytologic evaluation was verified by autopsy in 105 cases. Squamous carcinoma was found in 265 cases [58.2 per cent], accuracy was 87.9 per cent. Adenocarcinoma was found in 82 cases [18 per cent], accuracy was 100 per cent. Small cell carcinoma was found in 72 cases [15.8 per cent], precision of typing was 95.8 percent. Undifferentiated carcinoma was found in 36 cases [7.9 per cent], accuracy was 33.3 per cent. A overall accuracy of typing was 85.7 per cent. A concise characteristics of cytologic picture in basic types of lung carcinoma were presented. PMID- 2208328 TI - [Eosinophilic granulocytes and mastocytes in carcinoma of the uterine cervix]. AB - Presence of eosinophilic granulocytes and of mast cells were simultaneously evaluated in 40 cases of uterine cervix carcinoma. Mutual relation of major admixture of both cell types in total volume of infiltration failed to be proved. Participation of mast cells seemed to be mostly constant; their bigger admixture in single cases was not related to the shortest survival. Substantially greater number of eosinophilic granulocytes occurred only in the longest survival cases. PMID- 2208327 TI - [Cytological diagnosis of precancerous conditions and carcinoma of the uterine cervix]. AB - Study comprised 89,796 cytological smears and 113 cervical biopsies from patients cytologically screened during 4 years. Total of suspect and positive findings was 766 (0.86 per cent). Cytological diagnosis of precanceroses was correct in all cases. The screening identified 9 of 17 invasive carcinomas. Eight patients with invasive carcinoma showed a previous cytological negativity (47 per cent). False negative cytology in materials from different sources (different regional sampling gynaecologists) correlated with percentage of unrepresentative smears. PMID- 2208329 TI - [Complications and causes of death in heart transplantation]. AB - Complications and causes of death in patients with transplanted heart were analyzed in various intervals after operation. They comprised early deaths in the first week, short-time survival until one year, and long-time survival over one year. Acute heart failure of varied nature prevailed in early deaths as well as in long-time survival. In short-time survival, there were different causes of death in addition to heart failure. PMID- 2208331 TI - [Techniques and principles of histological diagnosis in osteopathies. Review and report of personal experience]. AB - Histological examination of bone samples from osteopathic patients with subsequent histomorphometric evaluations needs procedures a bit different from those of bioptic routine. They are introduced and summarized according to author's experience. A complete examination necessitates usage of technique for undecalcified samples after previous administering of tetracycline and of a sort of histomorphometric procedure. Routine diagnosis will manage even with decalcified samples supposing they were silver impregnated before decalcification; tetracycline as well as some metals (e.g. aluminium and iron) deposited in the bone will be eluted during decalcification. There are presented definitions and mean values of basic parameters evaluated in histomorphometric analysis. PMID- 2208330 TI - [Familial cerebral degeneration with myocardial involvement and dyserythropoiesis]. AB - A combination of dyserythropoietic anaemia, encephalopathy and cardiomyopathy was found in two siblings of different sex. They shared the same clinical history and pathomorphology what made authors suppose that it was a new not yet described syndrome with presumed autosomal recessive heredity. PMID- 2208332 TI - [Vascular mechanisms in the pathogenesis of multiple sclerosis]. PMID- 2208333 TI - [Neurology of the acquired immunodeficiency syndrome. II. Infections and tumors of the central nervous system]. PMID- 2208334 TI - [Present possibilities in the use of the EEG in neurotraumatology. 1. Conventional EEG]. PMID- 2208335 TI - [Evaluation of the effect of monitoring levels of antiepileptics on the effectiveness of epilepsy therapy using a computer]. AB - The authors describe a microcomputer programme which makes its possible to evaluate monitoring of antiepileptic levels. The programme makes it possible to put into computer input data on the patient, ensure their editing and printing, classification according to parameters selected in advance, tables of dosage and effectiveness of therapy, or else the computer selects certain parameters for statistical processing. It is thus possible to work with relatively large groups as the database has a capacity of 1000 patients. The programme is sufficiently flexible and contributes substantially to the objective evaluation of the effectiveness of therapy of epilepsy. PMID- 2208336 TI - [Comparison of the results of therapy with vinblastine iontophoresis in post diskectomy syndromes and other painful conditions]. AB - The authors tested in 36 patients treatment of chronic intractable pain by percutaneous iontophoretic administration of an inhibitor of microtubular transport, Vinblastine inj. (G. Richter, Hungary). The groups comprised: (1) 16 patients with severe radicular pain after one or several operations of prolapsed lumbar intervertebral discs, (2) 20 patients with severe pain in the area of radicular dermal zones or dermal innervation areas of peripheral nerves. In every patient a minimum of 15 procedures were tried. Evaluation of the therapeutic effect was based on subjective data of the patient on the mitigation of pain in per cent, on the intensity of the current pain and the interference of the intensity of pain with daily activities. According to all criteria improvement was achieved in 31 subjects, i.e. in 86%. A favourable effect of treatment was observed after the 8th-10th administration. In the first group of patients clinically significant mitigation of algic symptoms was achieved in 69% of the treated subjects. In the second group a therapeutic effect was achieved in 90% of the patients. A marked difference between the two groups was found with respect to mitigation of the intensity of pain on completion of treatment. The mean mitigation of pain intensity in the first group was 24.1%, in the second group 47.7%. This difference is highly significant. With the exception of one female patient always a positive effect at the site of administration (beneath the anode) was observed. PMID- 2208337 TI - [Personal experience with problems in cervical spondylotic myelopathy]. AB - The authors give an account of a group of 32 patients with the diagnosis of cervical spondylogenic myelopathy hospitalized in the course of three years at the neurological department of the District Institute of National Health, Zlin. The author describes a simple method of measurement of anteroposterior projections of the spinal canal. He also gives an account of the pathogenesis and therapeutic methods of this relatively frequent condition. Surgery is reserved for cases with permanent progression. PMID- 2208338 TI - [Specific aspects of mobility and changes in the shape of the dural sac in functional lumbosacral myelography]. AB - The purpose of the work was an analysis of lateral myelograms of the lumbosacral spine in the neutral position, in anteflexion and retroflexion from the aspect of the mobility of the dural sac and its relationship to the spinal canal. The group comprised 50 patients with clinically obvious discopathies and other vertebrogenic syndromes. The areas of the dural sac were measured planimetrically and evaluated by means of a computer. It was revealed: 1. The Soinal canal and dural sac are not static variables but dynamic ones. By movements of the lumbosacral spine the size of the dural sac changes and so does its shape. These phenomena can be evaluated not only qualitatively but also quantitatively. 2. The anteroposterior diameter of the dural sac on the myelograms in anteflexion and in retroflexion changes significantly, as compared with the neutral position, it increases during anteflexion and diminishes during retroflexion. 3. The area of the dural sac increases during anteflexion and diminishes in retroflexion, as compared with the neutral position. 4. Changes in the shape of the dorsal portion of the dural sac revealed in the segment of the discopathy are considered to be due to hypertrophy of the yellow ligaments. PMID- 2208339 TI - [Administration of morphine into the cerebral ventricles in chronic intractable pain]. AB - The study evaluated the effect of intraventricular morphine administration on chronic pain associated with malignant diseases in five subjects. To facilitate repeated application of the analgesic a reservoir was fixed subcutaneously on the calvaria with the catheter tip place in the lateral ventricle. The described approach made it possible to reduce substantially the dosage and to protract the action of morphine, as compared with intramuscular administration. No serious complications developed when the described mode of application was used. Because of the technically unpretentious procedure, the simple administration into the reservoir and the significant analgetic effect this method can be used in patients with malignant pain even in advanced stages of the disease. PMID- 2208340 TI - [Determination of inhibition habituation in the alpha rhythm (eyes open)]. AB - Luria used the term habituation for the phenomenon that the so-called orientation reflex to a certain stimulus is lost when the stimulus is repeated. In the present investigation habituation was tested by opening the eyes during conventional EEG. During the examination the patient was asked twelve times to open and close the eyes. Thus 730 patients aged 4 to 65 years were examined. Habituation developed in 542 patients and was absent in 188. Most frequently it developed between the 7th and 10th opening of the eyes, most frequently after the ninth. It seems thus that habituation of the alpha rhythm after this repetition is a normal bioelektrcical phenomenon and earlier, later or absent habituation is a deviation from the bioelectric norm. PMID- 2208343 TI - Lyme disease in Canada. PMID- 2208342 TI - [Is it possible to define and measure "quality of life"?]. PMID- 2208341 TI - [Drug therapy in cerebral infarct. Suggestion for a multicenter randomized therapy project]. PMID- 2208344 TI - Identification of the Lyme disease vector in Canada. PMID- 2208345 TI - Lyme disease in Manitoba? PMID- 2208346 TI - Adverse events temporally associated with immunizing agents--1988 report. PMID- 2208347 TI - Hepatitis B and HIV infections in dental professionals--British Columbia. PMID- 2208348 TI - Possible transmission of human immunodeficiency virus to a patient during an invasive dental procedure--United States. PMID- 2208349 TI - [Sexual abuse of children in the South Moravian Region 1985-1986]. PMID- 2208350 TI - [Personal experience with the placement of gypsy children in supplemental family care]. PMID- 2208351 TI - [Examination of children before liver transplantation]. PMID- 2208352 TI - [Abdominal epilepsy]. PMID- 2208353 TI - [Recurrently ill (infected) children in ambulatory practice]. PMID- 2208354 TI - [A vacation course for children with a tendency toward obesity]. PMID- 2208355 TI - [Possibilities of using acupuncture in pediatrics]. PMID- 2208356 TI - [Hereditary endogenous depression in a 10-year-old girl]. PMID- 2208357 TI - [Atopic dermatitis and asthma in children]. PMID- 2208358 TI - [Factors affecting the prognosis of acute lymphoblastic leukemia in childhood]. AB - The authors tried to test the value of some clinical and laboratory characteristics for the prognosis of acute lymphoblastic leukaemia (ALL) in a group of 69 children treated according to three different protocols. The results were evaluated by methods of one-dimensional and multidimensional analysis. The absolute number of blasts in the peripheral blood stream and initial leucocytosis during establishment of the diagnosis proved to be the most important risk factors influencing the prognosis of the patients. Other adverse signs for the prognosis of ALL in the group were a mediastinal tumour, L2 type of leukaemic blasts according to the morphological FAB classification and age above 10 years when the diagnosis was established. The patient's sex, immunophenotype of the leukaemic blasts, chromosomal abnormality of the karyotype in the leukaemic cells, marked hepatosplenomegaly, thrombocytopenia, haemoglobin values and PAS reaction in the blasts, did not affect the therapeutic results in the author's group of patients. PMID- 2208359 TI - [Relation between chronic respiratory diseases in children and secretory IgA and IgM]. AB - In 1981-1984 from a total of 288 children aged 6-36 months, suffering from acute and relapsing respiratory disease, in 52 children in the nasopharyngeal secretion IgM was detected in average amounts of 11.3 +/- 9.7 mg/100 ml. In 13 of the children in the course of 1-2 years after the first examination the IgM values in the nasopharyngeal secretion doubled or increased several times (20-50 mg/100 ml). The values in saliva at the age of 5-9 years were in seven of these children lower than the mean physiological values of SIgA in saliva (34.3 +/- 15.9 mg/100 ml). In 12 children in the course of 5-9 years chronic respiratory disease developed--obstructive bronchitis. In six children, where during school age in saliva mean SIgA values lower than normal were recorded, more frequent relapses and complications were recorded (pneumonia, sinobronchial syndrome, otitis media). Elevated values of SIgM in the nasopharyngeal secretion of infants and toddlers with acute and relapsing bronchitis can be considered a risk factor for the development of chronic disease, in particular in case of a permanently reduced SIgA formation also in saliva. PMID- 2208360 TI - [Supratentorial and infratentorial localization of brain tumors in various periods in childhood]. AB - The authors evaluated a group of 220 children (119 boys and 101 girls) aged 11 months to 15 years with histologically confirmed brain tumours hospitalized at the Clinic of Child Neurology, Childrens Hospital, Brno in 1953-1986. Tumours were diagnosed in infants 15 times, in 41 toddlers, in 72 preschool children, in 56 young school children and in 36 older school children. The ratio of supra- and infratentorial localization in infants was practically identical, in toddlers and preschool children there was a marked predominance of infratentorial tumours, in younger school age this localization was slightly predominating, in older school age supratentorial tumours predominated. The most frequent incidence of tumours throughout childhood was in the posterior cranial fossa from the cerebellar vermis, medulloblastomas being the most frequent type. In the supratentorial localization tumours in the temporal lobe predominated, astrocytomas being the most frequent type. PMID- 2208361 TI - [Etiology of acute diarrheal disease in a group of 0-3-year-old children]. PMID- 2208362 TI - [Claforan in the treatment of serious infections in children]. AB - To 63 critically sick patients on account of serious infection Claforan was administered. Forty-six patients were hospitalized at the intensive care and resuscitation unit and 17 patients suffered from oncological conditions. Claforan treatment was successful in 69.56% of the patients treated at the intensive care and resuscitation unit and in 30.44% in the group of oncological patients. PMID- 2208363 TI - [Microbial adherence, its significance for colonization of the intestine in neonates and possibilities of local defense]. PMID- 2208364 TI - [Characteristics of physical stress in children participating in sports at the present time]. AB - The author, head of the Clinic of Paediatric Sports Medicine, demonstrates in an article written for paediatricians the controversy between the phylogenetically based need of exercise and the inadequate practice in the ontogenesis of the present young generation. He explains from the theoretical and practical aspect basis concepts of adequate physical exercise in different age periods, the minimal need of physical activity, sports loads in different types of physical training and he emphasizes the importance of close cooperation between paediatricians and adolescence medical officers of the first line and at district policlinics with surgeries for sports medicine. PMID- 2208365 TI - [Physical education in schools]. AB - The article is a continuation of the preceding one written by prof. Kucera. It demonstrates the shortcomings of the contemporary system of teaching of physical training in our primary schools. Improvement will be achieved by collaboration of teachers and school medical officers--paediatricians, using modern teaching procedures and examination methods for the differentiation of children and for assessing a suitable physical training in our primary schools. Improvement will ren but also weaker ones should be engaged in physical training and that in the latter their health status is respected and the intensity of physical training adjusted. It is important to increase the prestige of the subject of physical training in primary schools and give it an equal place as to subjects of general education. PMID- 2208366 TI - Enantioselective synthesis of cyclohexenone derivatives by a chemicoenzymatic approach: stereo- and regioselective route to potential intermediates of compactin (ML 236B) and mevinolin. AB - As a synthetic application of the chiral monoester 2, prepared by pig liver esterase (PLE)-catalyzed hydrolysis of the corresponding meso diester 1, conversion of 2 into various cyclohexenone derivatives was examined. This paper describes the preparation of the isomeric cyclohexenones 6 and 7, potential intermediates for the synthesis of anti-hypercholesmic compactin (ML 236B) and mevinolin, under stereo- and regioselective control. PMID- 2208367 TI - Deprotection of the S-trimethylacetamidomethyl (Tacm) group using silver tetrafluoroborate: application to the synthesis of porcine brain natriuretic peptide-32 (pBNP-32). AB - Silver tetrafluoroborate (AgBF4) in trifluoroacetic acid (TFA) has been found to cleave the S-trimethyl-acetamidomethyl (Tacm) group or the S-acetamidomethyl (Acm) group without affecting other functional groups in a peptide chain. A newly isolated porcine brain natriuretic peptide-32 (pBNP-32) was synthesized by the combined use of the S-Tacm group and AgBF4 deprotection. The synthetic pBNP-32 was obtained in better yield by the AgBF4 procedure than by the standard I2 procedure. The synthetic pBNP-32 has the highest chick rectum relaxant activity among the known members of the atrial natriuretic peptide-brain natriuretic peptide (ANP-BNP) families. Somatostatin was also synthesized by the Fmoc-based solid-phase method using S-Tacm and AgBF4. In this synthesis, the recently developed reagent tetrafluoroboric acid (HBF4) was applied to cleave the peptide from the resin. PMID- 2208368 TI - The synthesis and antilipidperoxidation activity of 4,4-diarylbutylamines and 4,4 diarylbutanamides. AB - A series of 4,4-diarylbutylamine and 4,4-diarylbutanamide derivatives has been synthesized and evaluated for their antilipidperoxidation (ALP) activity and acute toxicity (LD50). Some of them were found to have significant ALP activity. PMID- 2208369 TI - Studies on penem and carbapenem. I. Syntheses and oral absorption of ester-type prodrugs of sodium (5R,6S)-2-(2-fluoroethylthio)-6-[(1R)-1-hydroxyethyl]penem-3-c arboxylat e. AB - Acyloxyalkyl esters (2a-d), alkyloxycarbonyloxyalkyl esters (2e-g) and (5-methyl 2-oxo-1,3-dioxol-4-yl)methyl ester (2h) of (5R,6S)-2-(2-fluoroethylthio)-6-[(1R) 1-hydroxyethyl]penem-3- carboxylic acid (1) were synthesized. Enhanced oral absorption was observed in mice reflecting increased lipophilicity, compared with the parent 1 itself. Among them, the ester 2h showed a prolonged plasma level and a large area under the blood concentration-time curve (AUC) in rats. These ester type prodrugs of penem 1 in phosphate buffer (pH 6.86) were much more stable than those of cephalosporins which easily degraded via isomerization to delta 2 cephalosporins. PMID- 2208370 TI - Studies on cardiotonic agents. I. Synthesis of some quinazoline derivatives. AB - A series of quinazoline derivatives with various 4-heterocyclylpiperidino groups at the 4-position was synthesized and tested for cardiotonic activity in anesthetized dogs. Among them, several 6,7-dimethoxyquinazoline derivatives showed potent cardiotonic activity. PMID- 2208371 TI - Inhibitory effects of tetramethylpyrazine and ferulic acid on spontaneous movement of rat uterus in situ. AB - Tetramethylpyrazine is one of the alkaloids contained in Ligusticum wallichii Franch. Ferulic acid is a phenolic compound contained in Ligusticum wallichii Franch and Angelica sinensis (Oliv.) Diels. The present study was carried out to examine the effect of tetramethylpyrazine and ferulic acid and the combined effect of both compounds on spontaneous uterine contractions in rats in situ. Tetramethylpyrazine and ferulic acid showed an inhibitory effect on uterine movement when given perorally and intravenously, respectively. The combination of both compounds, at doses individually insufficient to inhibit, synergistically inhibited uterine contraction. It was found that tetramethylpyrazine and ferulic acid inhibited uterine contractions and the inhibitory effect induced by the combination of both was due to the potentiation. PMID- 2208372 TI - An enzymatic assay method for D(-)-3-hydroxybutyrate and acetoacetate involving acetoacetyl coenzyme A synthetase from Zoogloea ramigera. AB - An enzyme assay method for D(-)-3-hydroxybutyrate and acetoacetate involving acetoacetyl coenzyme A (CoA) synthetase was developed. To determine the concentration of D-3-hydroxybutyrate, it was oxidized with D-3-hydroxybutyrate dehydrogenase in the presence of nicotinamide adenine dinucleotide (NAD+) to acetoacetate, which was then converted to acetyl CoA via acetoacetyl CoA through the combined actions of acetoacetyl CoA synthetase and 3-ketothiolase in the presence of adenosine triphosphate (ATP) and CoA. To determine the concentration of acetoacetate, acetoacetyl CoA generated from acetoacetate with acetoacetyl CoA synthetase was reduced to 3-hydroxybutyryl CoA with 3-hydroxyacyl CoA dehydrogenase in the presence of NADH. The amount of D-3-hydroxybutyrate or acetoacetate was estimated from the increase or decrease in the absorbance at 340 nm, respectively. The present assay method seemed to be accurate and quick. Furthermore, as to the assaying of D-3-hydroxybutyrate, the omission of hydrazine, which is included for the standard method, may be preferable for routine assaying. PMID- 2208373 TI - Preparative high-performance liquid chromatography on chemically modified porous glass. Isolation of saponins from ginseng. AB - Preparative high-performance liquid chromatography on octadecylsilyl porous glass (pore size, 550 A) with acetonitrile-water as the mobile phase was applied for the isolation of saponins from Panax ginseng. In a single run, several milligrams of pure ginsenosides were obtained from 10 g of roots of Panax ginseng. The method was simple, rapid and convenient and should be applicable to isolation of other saponins of crude drugs. PMID- 2208374 TI - Effects of glucocorticoids on deoxyribonucleic acid (DNA) synthesis stimulated by growth factors in cultured rat skin fibroblasts. AB - The effects of glucocorticoids on deoxyribonucleic acid (DNA) synthesis were studied by using confluent cultured rat skin fibroblasts prepared by enzymatic dispersion and expanded up to passage 3. Dexamethasone caused the inhibition of the DNA synthesis stimulated by 10% fetal calf serum (FCS) in a dose dependent manner. Maximum inhibition (90%-100%) was achieved by the concentration of 10( 7)M. A similar dose dependent inhibition was also obtained in the experiment using epidermal growth factor (EGF) (1 ng/ml) as a stimulant. Dexamethasone (10( 7)M) also inhibited the DNA synthesis stimulated by somatomedin C (100 ng/ml) or platelet derived growth factor (1 half-maximum unit/ml) almost to control levels. Binding studies with 125I-labeled EGF suggested that dexamethasone caused this inhibitory action without modulation of cell surface receptors for EGF. Furthermore, the effects of a variety of glucocorticoids on the DNA synthesis were studied to clarify the structural requirement of glucocorticoids for the inhibition of the DNA synthesis. The results showed that 11 beta-hydroxyl and 21 hydroxyl groups on the steroid nucleus were necessary for the inhibition of the growth factor-stimulated DNA synthesis. Meanwhile, the inhibitory action on the DNA synthesis was markedly diminished by the replacement of a 16 alpha-methyl group by a 16 beta-methyl group in the presence of a bulky group at C-17 (e.g. 17 alpha-valerate). For further elucidation of mechanisms of action of glucocorticoids on the inhibition of the growth factor-stimulated DNA synthesis, the relationships between the structural features of glucocorticoids and their binding ability to the glucocorticoid receptor ([3H]-dexamethasone-binding receptor) were studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2208375 TI - Effects of various triamines on cell-free polypeptide synthesis of Escherichia coli and on growth of its polyamine auxotrophs. AB - The effects of various synthetic triamines having a general structure, H2N(CH2)xNH(CH2)yNH2, where x = 2-5 and y = 2-8 (abbreviated, x-y; with 3-4 being spermidine itself), on poly(U)-directed polypeptide synthesis of Escherichia coli and on growth of its polyamine-requiring mutants were examined in comparison with those of spermidine. Except for 2-2 and 2-3, all of the triamines stimulated more or less polypeptide synthesis at suboptimal Mg2+ concentrations, but the Mg2+ concentration required for the maximal stimulatory effect was different for each triamine. The degree of maximal stimulation caused by 3-3 (norspermidine), 4-4 (homospermidine), or 4-5 was nearly comparable with that by spermidine. The acetylspermidines were inactive, however, they inhibited the spermidine stimulated polyphenylalanine synthesis. Many of the triamines examined reduced the ratio of leucine to phenylalanine incorporation into polypeptides during poly(U)-directed translation, and the degree of this effect did not necessarily correspond with that of the stimulatory effect. Moreover, 2-4, 2-5, 3-3 and 4-4 could stimulate the growth of a polyamine auxotroph of E. coli, MA 261, as effectively as did spermidine. However, 3-3 was the only triamine which could fully replaced spermidine in promoting growth of a mutant strain, KK 101, which is more dependent on polyamines than MA 261. Thus, these results demonstrated that some synthetic triamines were as active as spermidine in eliciting these effects, and also that there were some differences among these effects in the structural requirement for triamine. PMID- 2208376 TI - Accelerating effect of glutathione on hydroxylation of phenylalanine by stimulated polymorphonuclear leukocytes. AB - Sulfhydryl compounds significantly accelerated the hydroxylation of phenylalanine by stimulated polymorphonuclear leukocytes. The reduced form of glutathione (G SH) was most effective. The hydroxylation reaction in the presence of G-SH was largely prevented by superoxide dismutase and hydroxyl radical scavengers. The results suggest that a much faster production of hydroxyl radical may occur in a reaction mixture containing both G-SH and stimulated polymorphonuclear leukocytes than in that containing stimulated polymorphonuclear leukocytes alone. PMID- 2208377 TI - Alteration of glucose consumption and adenosine triphosphate content in bone tissue of rats with different ages: the stimulatory effect of zinc. AB - The alteration in bone metabolism at different ages was investigated by estimating glucose consumption and adenosine triphosphate (ATP) content in a culture system of bone tissue from 3- and 30-week-old rats. The femoral diaphyseal tissue was removed and cultured for periods up to 48 h in Dulbecco's Modified Eagle Medium. Bone tissue was incubated at 37 degrees C in 5% CO2/95% air in a medium containing either vehicle and zinc sulfate (10(-6) - 10(-4) M). The medium glucose consumed by bone tissue clearly increased in a 48 h-culture in 3-week-old rats, while the increase in 30-week-old rats was slight. The presence of zinc sulfate (10(-6) and 10(-5) M) caused a significant increase in bone glucose consumption in 3- and 30-week-old rats. ATP content in cultured bone tissue from 30-week-old rats fairly fell in comparison with that from 3-week-old rats. Bone ATP contents in 3- and 30-week-old rats were significantly increased by the presence of zinc (10(-4) M). The present findings suggest that bone energy metabolism deteriorates with increasing age, and that zinc has a stimulatory effect in elderly rats. PMID- 2208378 TI - Glucuronate-modified liposomes with prolonged circulation time. AB - For the purpose of obtaining liposomes with long circulation time in blood, we synthesized 1-O-palmityl-D-glucuronic acid (PGlcUA) and incorporated it into the liposomal membranes. The clearance of the PGlcUA-liposomes composed of dipalmitoylphosphatidylcholine (DPPC), cholesterol, and PGlcUA (40:40:20 as a molar ratio) from blood and their tissue distribution were compared with those of dipalmitoylphosphatidylglycerol (DPPG)-liposomes (DPPC/cholesterol/DPPG = 40:40:20). When [3H]inulin-loaded PGlcUA-liposomes and DPPG-liposomes were intravenously injected into rats, the half-life of the PGlcUA-liposomes in the blood appeared to be 1.7-fold longer than that of DPPG-liposomes. Radioactivities present in plasma and various tissues were measured 22 h after administration of these liposomes, and radioactivity remaining in the plasma was 2.5-fold greater when PGlcUA-liposomes were injected. The distribution pattern of [3H]inulin in PGlcUA-liposomes was similar to that in DPPG-liposomes. The radioactivity recovered in urine was 25% lower in rats treated with PGlcUA-liposomes than in those treated with DPPG-liposomes. Since both PGlcUA- and DPPG-liposomes exhibited similar size distribution and zeta-potential, glucuronic acid, rather than negative charge, on the liposomal surface appears to endow liposomes with a longer circulation time in the bloodstream. PMID- 2208379 TI - Characterization of two polysaccharides having activity on the reticuloendothelial system from the root of Glycyrrhiza uralensis. AB - Two polysaccharides, called glycyrrhizans UA and UB, were isolated from the root of Glycyrrhiza uralensis Fischer. They were homogeneous on electrophoresis and gel chromatography, and showed reticuloendothelial system-potentiating activity in a carbon clearance test. Glycyrrhizan UA is composed of L-arabinose: D galactose: L-rhamnose: D-galacturonic acid in the molar ratio of 20:14:1:3, and glycyrrhizan UB is composed of L-arabinose: D-galactose: D-glucose: L-rhamnose: D galacturonic acid in the molar ratio of 12:10:1:10:20, in addition to small amounts of O-acetyl groups and peptide moiety, respectively. About 10% (glycyrrhizan UA) and 35% (glycyrrhizan UB) of the D-galacturonic acid residues exist as the methyl esters. Methylation analysis, carbon-13 nuclear magnetic resonance and periodate oxidation studies indicated their structural features. PMID- 2208380 TI - New fatty monoesters of erythromycin A. AB - New fatty polyenic (linoleic, linolenic, arachidonic, linoelaidic) mono esters of erythromycin A have been synthesized by using various reagents such as acyl chloride, carboxylic acid anhydride, and mixed carbonic anhydride. These different ways of activating the fatty acid allowed a regioselectivity of esterification at position 2' of the desosamine ring or position 4" of the cladinose ring of erythromycin A. The in vitro antibacterial properties of these new esters against members of the resident flora of the human skin were determined and compared with those of erythromycin A. The number and the stereochemistry of the double bonds seem to play a crucial role in the expression of the in vitro antibacterial activity. PMID- 2208381 TI - Stability of urokinase in solutions containing sodium bisulfite. AB - The stabilities of urokinase (UK) in aqueous solution were investigated at pH 5.0 8.0 in the presence (1.0-3.0 x 10(-3) M) and absence of sodium bisulfite (SBS) both under scattered light (1000 lux) and in the dark using the fluorogenic substrate method. Increasing concentrations of SBS tended to increase the inactivation of UK. In the presence of SBS, with the increase in the pH value, UK gained in stability in the pH range of 5.0-8.0. The stability of UK in the presence of SBS in the dark was larger than that under scattered light, especially at pH 5.0. Therefore, it was suggested that the difference in the residual activities of UK between under light and in the dark was due to free radicals formed during the autooxidation of bisulfite under scattered light. UK was stabilized by glucose in the presence of SBS both under scattered light and in the dark. One reason for this phenomenon was postulated to be the formation of inactive bisulfite-glucose addition compound. The degradation products of UK during storage in a solution containing SBS were investigated by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. UK was revealed to be split into M.W. 36000 form and M.W. 20000 form by SBS. PMID- 2208382 TI - Indomethacin sustained-release suppositories containing sugar ester in polyethylene glycol base. AB - Indomethacin (IM) sustained-release suppositories were prepared by the fusion method using sugar ester and polyethylene glycol 4000 (PEG). The suppositories were evaluated by in vitro release testing, X-ray analysis and in vivo absorption testing in rabbits. X-ray analysis showed that IM was amorphous in PEG-base suppositories. In a release test, slow-release was obtained when the sugar ester content of a suppository was 60%. The IM plasma level following the administration of the suppository was well sustained in the absorption test. The main slow-release mechanism is considered to be the release of IM from the matrix composed of sugar ester and PEG, which is represented by the Higuchi equation. A good correlation between the release test and the absorption test was obtained. It is considered that the amorphous state of IM in this type of sustained-release suppository would enhance the release and absorption of IM in the rectum of the rabbit, whose rectal fluid volume is small. PMID- 2208383 TI - Effect of cyclodextrins on biological membrane. I. Effect of cyclodextrins on the absorption of a non-absorbable drug from rat small intestine and rectum. AB - The effects of three kinds of cyclodextrins (CyDs), alpha-, beta- and gamma-CyD on biological membranes were investigated by changes in absorption of a non absorbable drug, sulfanilic acid (SA), from the rat small intestine and rectum using an in situ perfusion technique. The absorption of SA from the intestine was slight and was not affected by the addition of CyDs. After pretreatment with a mucolytic agent, N-acetyl-L-cysteine (N-Ac), the absorption of SA was increased compared with SA alone in the presence of only beta-CyD. Similar treatment with sodium deoxycholate (SDC) and sodium lauryl sulfate (SLS) to gastro-intestinal membrane showed the enhanced absorption of SA by the addition of beta-CyD. The mucin layer on the surface of the gastro-intestinal membrane may play an important role in the absorption of drugs. On the other hand, enhanced absorption of SA from the rat rectum was not induced by beta-CyD with or without pretreatment with N-Ac, SDC or SLS. Simultaneously, the release of neutral sugars in the perfusate after treatment with adjuvants was also observed with N-Ac, SDC and SLS. These results indicate that the mucin layer works as a barrier to the increased absorption of SA by beta-CyD. PMID- 2208384 TI - Characterization of drug binding sites on alpha 1-acid glycoprotein. AB - The classification of drug binding sites on alpha 1-acid glycoprotein (AGP) was studied by displacement experiments using fluorescent probes. Basic drugs not only displaced basic probes strongly but also acidic probes as well. Acidic probes, on the other hand, were displaced by some acidic drugs such as phenylbutazone and sulfadimethoxine which had no effect on most of the basic probes. This contradiction suggests that the basic drugs do not completely share a binding site with the acidic drugs. The polarity of the basic drug binding site was higher than that of the acidic drug binding site. The negative charges were probably located in or near the former, different from the latter. The basic drug binding site was more sensitive to the conformational change of AGP. It seems that there are particular drug binding sites on the AGP molecule for acidic and basic drugs. However, all the displacement data do not fully support the possibility of two independent drug binding sites. Therefore, it is rather reasonable to consider that these sites are not completely separated but are significantly overlapped and influenced by each other. Accordingly, AGP seems to have one wide and flexible drug binding area. PMID- 2208385 TI - Method of kinetic analysis of photodegradation: nifedipine in solutions. AB - A rate equation for photodegradation was derived from Lambert-Beer's law and Grotthus-Draper's law: -dc/dt=k1(1-exp(-(k2c+k3(c0-c))))k2c/(k2c+k3(c0-c)) where c is the concentration of reactant, c0 is the initial concentration of reactant, t is time, k1 is the rate constant, and k2 and k3 are the absorption coefficient of reactant and its photodegradation product, respectively. In a case where the photodegradation products have no photoabsorption, k3 assumes the value of zero in the above general equation. In a case where the photodegradation products have the same spectrum and molar absorptivity as that of the reactant, k3 assumes the value of k2, and hence the photodegradation is not a first-order reaction; however, the equation itself gives the pseudo-first-order reaction rate equation. In a case where the concentration of reactant is high enough, the equation approaches a zero-order reaction rate equation. The photodegradation rate of nifedipine in solutions under a germicidal lamp, near an ultraviolet fluorescent lamp and a fluorescent lamp was analyzed using the above equation. The photodegradation rate was directly proportional to the amount of light absorbed, and fitted well with the equation. The above theoretical equation was substantiated by the photodegradation of nifedipine, and hence is expected to apply to other photosensitive drugs. PMID- 2208386 TI - In vivo and in vitro metabolism of cannabidiol monomethyl ether and cannabidiol dimethyl ether in the guinea pig: on the formation mechanism of cannabielsoin type metabolite from cannabidiol. AB - Oxidative metabolism of cannabidiol monomethyl ether (CBDM), one of the components of marihuana, was studied in the guinea pig. Cannabielsoin monomethyl ether (CBEM) was found to be formed with hepatic microsomes by gas chromatography mass spectrometry (GC-MS). Experiments using various modifiers of enzymatic reaction suggested that, as in the case of cannabielsoin (CBE) formation from canabidiol (CBD), CBEM was formed from CBDM by the monooxygenase system including cytochrome P450. When cannabidiol dimethyl ether (CBDD), in which phenolic hydroxyl groups of CBD are masked with methyl groups, was incubated with liver microsomes and an reduced nicotinamide adenine dinucleotide phosphate-generating system, 1S,2R-epoxy-CBDD was identified by GC-MS. The epoxy metabolite was also found in the liver of a guinea pig pretreated with CBDD (100 mg/kg, intraperitoneally) 1 h before sacrifice. Rate of 1S,2R-epoxide metabolism was slower than that of 1R,2S-epoxy-CBDD under the conditions, as in the microsomal oxidation of CBDD described above. These results indicate that 1S,2R-epoxides are formed from CBD, CBDM and CBDD and that the epoxides are quickly converted to elsoin-type metabolites in the cases of CBD and CBDM. PMID- 2208387 TI - Solution synthesis of human peptide YY (hPYY). AB - Human peptide YY (hPYY) was synthesized in a conventional manner by assembling six peptide fragments followed by deprotection with 1 M trimethylsilyl trifluoromethanesulfonate (TMSOTf)-thioanisole in trifluoroacetic acid (TFA). After purification by gel-filtration on Sephadex G-25, followed by reversed-phase high-performance liquid chromatography, a highly purified sample of synthetic hPYY was obtained. When administered in dogs, synthetic hPYY was as active as synthetic porcine PYY in terms of the effects on systemic arterial blood pressure, and splanchnic blood flow. PMID- 2208388 TI - Synthesis and in vitro affinity for dopamine D-2 receptor of N-fluorine substituted analogs of eticlopride. AB - With the aim of developing fluorinated benzamides that may be useful as radioligands for positron emission tomography, fluorine analogs of eticlopride, in which the N-ethyl group was replaced by 2-fluoroethyl, 3-fluoropropyl and p fluorobenzyl groups, were synthesized. These derivatives were tested for their ability to displace [3H]spiperone from its specific dopamine D-2 receptor. Their potencies were decreased when compared with eticlopride, but the two fluoroalkylated analogs were in the same order of magnitude as that of haloperidol. PMID- 2208389 TI - Increased gamma-aminobutyrate aminotransferase activity in brain of patients with Alzheimer's disease. AB - In order to search for more proximal factors in the pathogenesis of Alzheimer's disease, we studied the activities of various enzyme in the brains of patients, as well as control cases, by postmortem autopsy. In addition to the findings already known, such as the increase in prolyl endopeptidase (post-proline cleaving enzyme, PPCE) activity and the decrease in kallikrein activity, we found, anew, an increase in aminobutyrate aminotransferase (GABA-T) activity in the Alzheimer brain. This may be an important impetus for the reduction of gamma aminobutyric acid (GABA) in the brain, one of the neurotransmitters. It has to be determined whether the former two abnormalities offer a background for such an abnormality of the neurotransmitter. PMID- 2208390 TI - Increase in aminobutyrate aminotransferase and cholineacetyltransferase in cerebrum of aged rats. AB - We previously reported an increase in aminobutyrate aminotransferase (GABA-T) activity in the cerebrum of Alzheimer patients. In the present study, we investigated whether such findings are common in the usual aging process as well. We examined the activity of various enzymes, which were examined in the previous study, in the cerebrum of Wistar-Kyoto rats and spontaneously hypertensive rats. In the two strains, we compared the enzyme activities between the two groups of animals, 5 weeks and 13 weeks of age. In both strains, the older animals had significantly higher activities of GABA-T and choline acetyltransferase (ChAc-T). In spite of other enzymatic changes coexisting, the above two enzymes were suggested by discriminant function analysis to be playing a major role in the multiple enzymatic changes in the cerebrum of the animals. PMID- 2208391 TI - Measurement of gastric pH during digestion of a solid meal in dogs. AB - The behavior of gastric pH during digestion of a solid meal in beagle dogs was determined by use of an ion-selective field effect transistor pH sensor. The pH in the stomach was 3.9 +/- 0.4 (mean +/- S.D., n = 6) at 0.5 h after meals. It was maintained at a mildly acidic (about pH 3) level for long periods. PMID- 2208392 TI - Statistical evaluation of accelerated stability data obtained at a single temperature. I. Effect of experimental errors in evaluation of stability data obtained. AB - Accelerated stability data obtained at a single temperature is statistically evaluated, and the utility of such data for assessment of stability is discussed focussing on the chemical stability of solution-state dosage forms. The probability that the drug content of a product is observed to be within the lower specification limit in the accelerated test is interpreted graphically. This probability depends on experimental errors in the assay and temperature control, as well as the true degradation rate and activation energy. Therefore, the observation that the drug content meets the specification in the accelerated testing can provide only limited information on the shelf-life of the drug, without the knowledge of the activation energy and the accuracy and precision of the assay and temperature control. PMID- 2208393 TI - Statistical evaluation of accelerated stability data obtained at a single temperature. II. Estimation of shelf-life from remaining drug content. AB - Accelerated stability data obtained at a single temperature (40 degrees C) is statistically evaluated and the utility of the actual value of remaining drug content observed in the test for estimation of shelf-life is discussed. The distribution of the time required for 10% degradation at 25 degrees C, t90(25), is calculated from the observed drug content, taking the experimental errors into consideration. The probability that the t90(25) is longer than a specified shelf life, which is calculated from the distribution, is represented as a function of the observed drug content. The probability was found to depend on the experimental errors in the assay and temperature control as well as in the activation energy of degradation (Ea). The relationship between the observed drug content and the shelf-life assured with a certain probability is shown graphically, so that one can reasonably predict the expected shelf-life as a function of Ea if the accuracy and precision of the assay and temperature control are known. PMID- 2208394 TI - Phenolic compounds from stem bark of Acanthopanax senticosus and their pharmacological effect in chronic swimming stressed rats. AB - Ten phenolic compounds, isofraxidin (1), (+)-syringaresinol-di-O-beta-D-glucoside (2), syringin (3), chlorogenic acid (4), isofraxidin-7-O-beta-D-glucoside (5), 2,6-dimethoxy-p-benzoquinone (6), (+)-pinoresinol-O-beta-D-glucoside (7), (7), (+)-syringaresinol-O-beta-D-glucoside (8), (+)-pinoresinol-di-O-beta-D-glucoside (9) and (+)-medioresinol-di-O-beta-D-glucoside (10), were isolated from the stem bark of Acanthopanax senticosus Harms and identified, respectively. The aqueous extract of the stem bark exhibited a prolonging effect on the exercise time to exhaustion in chronic swimming stressed rats. The effect on the exercise time in the chronic swimming stressed rats was respectively tested for compounds 2 and 4, which are major constituents of the stem bark. As a result, it was indicated that compound 2 is the compound responsible for part of the pharmacological effect which the aqueous extract of the stem bark showed. PMID- 2208395 TI - Synthesis of biologically active derivatives of D-glucosamine-4-phosphate and 1 thyminyl-D-glucosamine-4,6-disulfate. AB - New 1-thyminyl-D-glucosamine-4-phosphate and 1-thyminyl-D-glucosamine-4,6 disulfate derivatives were synthesized. The 1-thyminyl-D-glucosamine-4,6 disulfate derivative showed antiviral activity against HIV. PMID- 2208396 TI - Synthesis of a new chemically stable prostacyclin analogue with high and long lasting activity. AB - The chemically stable prostacyclin analogue (Z)-4,5-didehydroisocarbacyclin analogue (6) has been synthesized. Compound 6 given intravenously or orally is very potent in inhibiting platelet aggregation. PMID- 2208397 TI - Two new potent inhibitors of xanthine oxidase from leaves of Perilla frutescens Britton var. acuta Kudo. AB - A known and a new caffeic ester (1 and 2), new inhibitors of xanthine oxidase (XO), were isolated from leaves of Perilla frutescens var. acuta and their structures have been established as (Z,E)-2-(3,4-dihydroxyphenyl)ethenyl ester (1) and (Z,E)-2-(3,5-dihydroxyphenyl)ethenyl ester (2) of 3-(3,4-dihydroxyphenyl) 2-propenoic acid, respectively, based on detailed spectral studies, including 2D COSY, long range COSY, difference NOE, etc. Both caffeic esters strongly inhibited XO in vitro and especially, the inhibition by 1 was as potent as that by allopurinol. The inhibition mode of 1 was also shown to be non-competitive. PMID- 2208398 TI - [Use of a "leakage detector" to test minute holes in gloves]. PMID- 2208400 TI - [Evaluation of nursing care of cancer patients]. PMID- 2208399 TI - [The uses of "ma-kuo tincture"]. PMID- 2208402 TI - [Communication skills of psychiatric nurses]. PMID- 2208401 TI - [Nursing care of comatose patients with hyperosmotic diabetes]. PMID- 2208403 TI - [Nursing care after thymus transplantation in patients with advanced liver cancer]. PMID- 2208404 TI - [Work at the consultation office for psychological care]. PMID- 2208405 TI - [Care of gonorrhea patients]. PMID- 2208406 TI - [Early treatments of intravenous leakage]. PMID- 2208407 TI - [Experimental study of preventing induration due to intramuscular injection]. PMID- 2208408 TI - [Nursing care of adult primary hypothyroidism]. PMID- 2208409 TI - [Nursing care of forest encephalitis, mild and serious cases]. PMID- 2208410 TI - [Nursing care of patients treated by hepatic artery infusion embolization with complications]. PMID- 2208411 TI - [Monitoring and analysis of arrhythmias occurring 24 hours after cardiovascular surgery]. PMID- 2208412 TI - [Phototherapy of neonatal hyperbilirubinemia]. PMID- 2208413 TI - [Management of the nursery for children with hepatitis]. PMID- 2208414 TI - [Importance of nurses' observations of their patients' conditions]. PMID- 2208415 TI - [Effects of Codonopsis pilosulae on the synthesis of thromboxane A2 and prostacyclin]. AB - 24 angina pectoris patients were treated with Codonopsis pilosulae (CP) oral solution 20 ml (containing crude CP 20 g) thrice daily for 7 days, other 10 cases were treated by aspirin 0.5 g per day for a week as the control group. After treatment, in the CP group, the plasma level of TXB2 was obviously reduced from 156.76 +/- 11.87 pg/ml to 125.01 +/- 8.85 pg/ml (means +/- S means), the inhibitory rates was 15. 67% (P less than 0.05), and of 6-keto-PGF1 alpha (6-K) was not markedly changed (P greater than 0.05). In the aspirin group, TXB2 was also reduced significantly (P less than 0.05); 6-K was reduced more than that of CP group, the inhibitory rate was 24.33 +/- 9.40% (P less than 0.05). To reveal the mechanism of CP action on the synthesis of TXA2 and PGI2, the porcine lung microsome was used as the donor of cyclooxygenase, thromboxane synthase and prostacyclin synthase, the effects of CP on the formation of TXB2 and 6-K from arachidonic acid (AA) or endoperoxides were measured by RIA respectively. The results showed that both the levels of the formation of TXB2 from AA or endoperoxides were markedly reduced by CP in a dose-dependent (at doses of 3-300 mg/ml). The synthesis of TXB2 was distinctly inhibited alone with a dose of 100 mg/ml CP, which suggested that CP might be an inhibitor of TXB2 synthase at that dose; while at a dose of 300 mg/ml CP, the synthesis of TXB2 and 6-K were inhibited simultaneously (P less than 0.001). It showed that a larger dosage of CP, which could inhibited the synthesis of both TXA2 and PGI2, its mechanism of action needs further study. PMID- 2208416 TI - [Clinical study on xintongkang capsule in treating angina pectoris of coronary heart disease]. AB - Two hundred and sixty seven cases of angina pectoris of coronary heart disease (male 152, female 115, age 41--79) were studied. Among these, 195 cases were patients with effort angina, 72 cases with non-effort angina. Double blind stratified randomized grouping, differentiation- syndromes treatment of TCM and self-control observation methods were applied. The results showed that total effective rate was 93.3% for angina pectoris in the treatment group. While control group which were treated by persantin and aspirin was 54.7% (P less than 0.001). For resting ECG evaluation total effective rates were 52.78% and 13.51% respectively. The ECG exercise testing (protocol Bruce) and dynamic ECG also showed the results similar to that of resting ECG. According to differentiation syndromes treatment of TCM. The effect of Xintongkang capsule on simple stagnation of Qi and stasis of blood, or combined with deficiency of Qi, or combined with deficiency of Yin was better than other symptoms. The effect of Xintongkang capsule initiated in the second week after oral medicine, peak response occurring in the fourth week, and it trend to the stability in the eighth week. There was no harmful effect to heart, liver, kidney and blood. No allergic reactions were found in this observation. PMID- 2208417 TI - [Relation of cytochemistry changes in the peripheral blood ANAE in chronic glomerulonephritis and differentiation-syndromes]. AB - The ANAE reaction of the peripheral blood from 24 patients of chronic glomerulonephritis (grouped according to the identification of TCM) and 30 normal individuals were observed by cytochemistry and microspectrophotometry. It was found that the percentages of positive lymphocytes of the deficiency of Kidney Yin was 47.8 +/- 7.6%, among which the percentages of lymphocytes of spot granular pattern and scattered granular pattern were 42.4 +/- 6.3% and 5.4 +/- 2.2% respectively, the ANAE relative quality of monocytes of the deficiency of Kidney-Yin was 51.26 +/- 2.59. They were 39.7 +/- 7.4%, 31.2 +/- 5.8%, 8.5 +/- 2.7% and 41.84 +/- 2.66 respectively in the deficiency of Kidney-Yang. The results of normal group were 65.5 +/- 6.8%, 53.6 +/- 6.7%, 11.9 +/- 3.4% and 54.78 +/- 3.34 in their given order. The differences in three groups each other were marked significantly. The authors have found the difference between the patients of chronic glomerulonephritis and the normal individuals was significant statistically. PMID- 2208418 TI - [Effect of baoshen wan on serum lipid peroxide levels in nephritis treated based on the differentiation-syndromes]. AB - This paper deals with the treatment of 22 cases of chronic nephritis with Baoshen Wan (protecting kidney pills) according to the differentiation of syndromes; the results showed that 3 cases had got perfect remission, 6 cases fundamental remission, and 10 cases partial remission; thus its effective rate reached to 86.4%. Before treatment, the mean value of serum LPO of the 22 patients was 4.44 +/- 0.099 (means +/- S means, mumol/L), which compare with the normal value (3.69 +/- 0.075), P less than 0.05. After treatment, the serum LPO level was lowered to 3.95 +/- 0.11, P less than 0.05. It suggested that Baoshen Wan could disperse the free radical and lower the serum LPO level in the patients with chronic nephritis. PMID- 2208419 TI - [Effect of blood-activating and stasis-removing drugs on hypercoagulability data in nephrotic syndrome]. AB - Platelet aggregation test (PAgT), plasma factor VIII related antigen (VIII R:Ag) and kaolin partial thromboplastic time (KPTT) in 32 nephrotic children were determined. RESULTS: (1) PAgT induced by ADP and adrenaline which included 1 minute and 5 minute aggregation rate in the patients (30. 78 +/- 7.44%, 72.56 +/- 18.09%, 22.16 +/- 9.24%, 67.53 +/- 22.32%) was significantly increased (P less than 0.02-0.001) as compared with the normal control group (30.65 +/- 8.38%, 57.98 +/- 13.60%, 18.14 +/- 7.33%, 55.92 +/- 16.10%) except 1 minute aggregation rate induced by ADP (P greater than 0.05). (2) VIII R:Ag and KPTT in patients (226.97 +/- 50.47%, 32.04 +/- 5.88 sec) were obviously different (P less than 0.001, P less than 0.02) from the normal control group (107.11 +/- 24.55%, 35.42 +/- 5.00 sec). The results suggested that PAgT, VIII R:Ag and KPTT could be used as laboratory data reflecting the hypercoagulable state in nephrotic children. According to their age, sex and the clinical types of nephrotic syndrome, 24 nephrotic children with abnormality of PAgT, VIII R:Ag and KPTT were random divided into group 1 given prednisone only and group 2 given prednisone, blood activating and stasis-removing drugs. RESULTS: the difference of PAgT, VIII R:Ag and KPTT in two groups between pre- and post-treatment was significant statistically (P less than 0.05-P less than 0.001). The decline in PAgT and VIII R:Ag was faster in group 2 than in group 1 (P less than 0.05-P less than 0.01). The results showed that blood-activating and stasis-removing drugs were likely to improve abnormal PAgT and VIII R:Ag in nephrotic children. PMID- 2208420 TI - [Effects of danggui shaoyao powder on blood rheological indexes and prostaglandin F2 alpha in dysmenorrhea patients]. AB - The results showed that several blood rheological indexes of dysmenorrhea patients were abnormal, the contents of plasma prostaglandin F2 alpha (PGF2 alpha) and menstrual blood PGF2 alpha of the patients were significantly higher than those of the normal women. The abnormal indexes were recovered to normal range after the patients had been treated with Danggui Shaoyao Powder for 3 months. Danggui Shaoyao Powder had better actions of improving the abnormal indexes than Tianqi Dysmenorrhea Capsule did. PMID- 2208422 TI - [Clinical studies of fuma anti-rheumatoid arthritis tablets]. PMID- 2208421 TI - [Clinical comparative study of intravenous piperacillin sodium or injection of scutellaria compound in patients with pulmonary infection]. AB - In this survey, 60 patients with pulmonary infection (mainly nosocimial pneumonia) were divided into two groups randomly. 30 patients treated by injection of Scutelleria compound and 30 patients by intravenous piperacillin sodium as control. Before treatment there was no significant difference of clinical data between two groups. The total efficacy was evaluated after treatment for one week. 40%, 36.7% were marked effective in corresponding. 33.3%, 40% were effective and 26.7%, 23% were ineffective respectively. Total effective rates were 73.3% and 76.7% in corresponding group. Temperature was average decreased for 7.43 +/- 3.02 and 7.63 +/- 5.79 days, symptoms disappeared or relieved for 11.67 +/- 6.75 days and 11.53 +/- 7.30 days, leucocyte decreased to normal on 9.03 +/- 6.53 days and 10.13 +/- 6.23 days, roentgenographical shadows disappeared or became smaller for 16.1 +/- 7.02 days and 16.1 +/- 9.88 days in corresponding group. There were no side-effect of the functions of liver, kidney and medulla ossium in two groups. In piperacillin sodium group, fungal infection were found in 4 of 30 patients, but there was no any case suffered from fungal infection in injection of Scutelleria compound group. It was suggested that injection on Scutelleria compound is a hopeful preparation and should be studied further. PMID- 2208423 TI - [Clinical therapeutic effect of xifukang in 53 patients with silicosis]. AB - Xifukang is a compound preparation of Chinese herbs consisting of Hanbane grugs mainly. Since 1987, the significant efficiency have been obtained in treatment of 53 patients suffering from silicosis by self-control study. The results indicated that the clinical manifestations including dyspnea, cough, sputum production, chest pain, weakness, etc. were markedly improved (P less than 0.01) and measurements of pulmonary function (FVC, FEV and MVV) significant enhanced (P less than 0.01). After treatment 20 cases roentgenogram exam showed that the lung's clarity and the limited emphysema were improved, the silicolic nodule and mass-mergence opacity of 3 cases lessened in some degree. By discussing the effect of Xifukang which might lower the collagen protein content of experimental silicosis of Wistar rats and improve pathomorphous. The authors concluded that the therapeutic mechanism of Xifukang could be the actions of this remedy on promoting blood circulation to eliminate blood stasis dredging microcirculation, increasing ventilation/perfusion (VA/Q), protecting dust-cells, resisting fibrosis, regulating immune function, enhancing lung clearance, postponing and preventing development of silicosis. PMID- 2208424 TI - [Detection of the anti-cancer biological effect of naphthoquinone pigment-LIII]. AB - Naphthoquinone pigment-LIII, an extract from Arnebia euchroma, could apparently inhibit the proliferation of stomach cancer cell line and esophagus cancer cell line. At the effective concentration of 5 micrograms/ml, the mitotic index and growth curve declined without showing any damage to human normal cells. At 5-10 micrograms/ml, the colony efficiency of cancer cells became significantly low. The anti-cancer effect of Naphthoquinone pigment-LIII might be related to its role of influencing the amount of RNA and ultrastructure of cancer cells which was discussed in this paper. PMID- 2208425 TI - [Adjustable action of pi-shen recipe on immune function in mice with L1210 ascites]. AB - Proliferation of Con A stimulated splenic lymphocyte was examined by incorporation of 3H-thymidine. Fluorescence polarization of DPH labelled splenic lymphocyte and bone marrow cells was measured. Proliferation of Con A stimulated splenic lymphocyte in DBA inbred healthy mice was higher than that of L1210 mice but fluorescence polarization of DPH labelled splenic lymphocyte in same healthy mice was lower than that of L1210 mice. i.e. membranous lipid lymphocyte fluidity of lymphocyte in the healthy mice was smaller than that of L1210 mice. 9 days after administration of Pi-Shen recipe by tube stomach proliferation of Con A lymphocyte in the healthy mice has been increased. The recipe adjusted splenic lymphocyte membrane lipid fluidity of L1210 mice to level of those in healthy mice. Effects of Pi-Shen recipe on lipid fluidity of bone marrow cell membrane of L1210 mice were almost similar to that in splenic lymphocytes. These studies suggest that the mechanism on adjustable role of Pi-Shen recipe on T-lymphocyte function related to lymphocyte membrane lipid fluidity. PMID- 2208426 TI - [Anti-cancer effects of sanjie pellets]. AB - In the present paper, the authors applied Sanjie pellet in the anti-cancer study on the animals. The results indicated that in the extracorporeal experiment, stomach perfusion with Sanjie pellet 12.5g/kg daily for 10 successive days, the inhibitory rate for the substantive liver cancer was 84%. For ascites liver carcinoma, it could raise the average rate of prolonging life span to 76%. Lethal dose (LD50) was 25 g/kg. The pathological observations indicated that Sanjie pellet acted directly on the cell membrane and organelle of the liver cancer cells and causing lysis of the cell membrane, dilation of rough surface endoplasmic reticulum, the swelling of mitochondria and disintegration of the liver cancer cells body. The authors concluded that these were the main pharmacological efficacies of Sanjie pellet. PMID- 2208427 TI - [Inhibitory effect of liuwei dihuang decoction on induced mutation and spontaneous tumor]. AB - Anti-mutagenic activity was evaluated with micronuclear test. It appeared to be same between the result of mice treated with 10 g/kg Liuwei Dihuang decoction (LWDHd) for 3 days and that with 34.5 g/kg for 10 days. All the permillages of micronuclear appearance of treated groups were less than that of controls. The intercept (A) value of dose-effect curve were 12.7 and 9.4 as treated with cyclophosphamide (Cy) alone, but 1.2 and 3.2 as orally administered with LWDHd before injecting Cy. It showed that LWDHd could inhibite mutagenic activity of Cy. The affection of LWDHd on spontaneous tumorigenesis was observed in LACA mice. The tumor incidence rate was 9.0% in the control mice observed for 60 weeks, but 5.0% in the animal feeding LWDHd in food. The tumor incidence rate of big dose group was 1.0% and the difference was significant between it and that of the control (P less than 0.01). PMID- 2208428 TI - [Advanced study of calcium channel blockers in Chinese herbal medicine]. PMID- 2208429 TI - [Deficiency syndrome of chronic gastritis]. AB - 161 cases of chronic gastritis (including 59 superficial gastritis, 86 atrophic gastritis, 16 superficial gastritis combined with atrophic gastritis) typed in deficiency syndrome (including 64 Spleen-deficiency syndrome, 97 Spleen-Kidney deficiency syndrome) were studied clinically with modern medicinal multiple index. The gastroscope image, pathologic changes of gastric mucosa, stomach barium meal examination, gastric acid, serum gastrin, urine pepsinogen, urine 17 ketosteroid, vegetative nerve function, peripheral blood picture, etc. were selected as observation indices. The preliminary findings showed that in Spleen deficiency patients, the superficial gastritis constituted the majority, the asthenic stomach constituted the minority, the gastric secretion and the serum gastrin were on the high side, the urine pepsinogen, the adrenocortical function and the hemoglobin were on the low side, but the white blood cell was rather normal; otherwise, in Spleen-Kidney deficiency patients, the atrophic gastritis and the asthenic stomach constituted the majority, the gastric secretion decreased, the serum gastrin level was higher, while the urine pepsinogen, the adrenocortical function, white blood cell and the hemoglobin were on the low side. It was also found that in certain same inflammation changes, the gastric secretion of the Spleen-Kidney-deficiency syndrome was markedly than that of Spleen-deficiency syndrome. With the treatment method of invigorating the Spleen and reinforcing the Spleen-Kidney, each index was relatively improved. The degree of seriousness to inflammation changes of gastric mucosa and the disturbance or imbalance of gastric secretion function were reflected from the Spleen-deficiency and the Spleen-Kidney-deficiency syndromes of chronic gastritis. It is suggested that hemopoiesis and hypothalamo-adenohypophysial-adrenal cortical axis be influenced. PMID- 2208430 TI - [Relation between endoscopy, radionucleotide scintigraphy and traditional Chinese medicine in 39 patients with reflux esophagitis]. AB - Histological biopsy and radionucleotide scintigraphy (RNS) were carried out in 39 patients with symptoms and esophagoscopy evidence of gastroesophageal reflux disease. The detective rates were 74% and 79% respectively. The mechanism were discussed. There was no correlation between histological changes, RNS and clinical TCM types based on the theory of TCM. PMID- 2208431 TI - [Preliminary study of therapeutical mechanism on chyluria by heat-cleaning and hemostasis drugs]. AB - Ten cases of filarial chyluria were treated with Chinese medical herbs. The results showed that the average concentration of serum histamine of 142 ng/ml before treatment dropped to 93 ng/ml after treatment. The average lymph-vessel pressure of 9.93 cmH2O in dorsalis pedis dropped to 4.74 cmH2O after cure. The prevalent microcirculation obstacle of medium to serious grade also was improved or recovered. The average serum viscosity of 1,884 before treatment dropped to 1,725. These results indicated that the chronic lymphatic inflammation occurring in pelvis or behind peritoneum due to perennial stimulation of adult filariae, caused the high concentration of inflammatory medium tissues, the expansion of micro-vessels and the increase of lymph-vessel pressure. Therefore, the microcirculation obstacle was the principle pathogeny of filarial chyluria. PMID- 2208432 TI - [Change in serum growth hormone in aged men and effect of kidney-warming and yang restoring drugs]. AB - Basal and sleeping levels of serum growth hormone (GH) were measured in aged men and young men. GH levels after an intravenous bolus of growth hormone releasing hormone (1 microgram/kg) were also determined in healthy aged men with mild Kidney-Yang deficiency. The effect of Chinese herbs with Kidney-warming and Yang restoring function was observed. The basal GH value in aged men was not significantly different when compared with young men, but the GH value during sleep evidently decreased (P less than 0.05). The response of GH to GRF was obviously decreased as compared with young people. The GH level following GRF stimulation was significantly different from that of young men. The Kidney warming and Yang-restoring Chinese herbs could alleviate the symptoms of Kidney Yang deficiency in aged men. The sleep value of GH and response of GH to GRF were increased after taking Chinese herbs. It suggested that the decrease of pituitary reserve might probably be the pathogenesis of Kidney deficiency. Together with the results of another animal experiments, the authors presumed that the Chinese herbs with Kidney-warming and Yang-restoring characteristics might effect through the increase of hypothalamic dopamine and the subsequent improvement of pituitary hormone reserve. PMID- 2208433 TI - [Effect of yiqi-yangyin prescription on bile composition of cholelithiasis patients]. AB - There were 41 postoperative patients of cholelithiasis with manifestation of Qi Yin deficiency, had treated with Yiqi Yangyin Prescription. The regimens was 2 weeks as a course, thereafter bile specimens were taken through T tube drainage, and biochemical analysis were performed in order to determine the composition in consequence of the comparison of the treated patients with the control groups. There were 19 patients of bile pigment stone in whom 10 treated with the prescription and 9 were served as control. The results showed that the total bilirubin, unconjugated bilirubin, the concentration of calcium ion and the activity of beta-glucuronidase were markedly decreased as compared to those in the control group (P less than 0.05), the concentration of bile acid markedly increased than that in the control group (P less than 0.05). There were 22 patients of cholesterol stone, 11 treated with the prescription and 11 were served as control group. The results were the same as in bile pigment stone group except decreased in conjugated bilirubin (P less than 0.05), and the unconjugated bilirubin were remained unchanged (P greater than 0.05) as compared to the control group. The ratio of unconjugated bilirubin to total bilirubin and the ratio of bile acid to bilirubin were markedly decreased as compared to those in the control group. The above observation showed promptly that Yiqi-Yangyin Prescription gave a promise influence on lithogenic bile of cholelithiasitic patients, and also investigated the mechanism of the prescription used for deficiency patients with biliary troubles. PMID- 2208434 TI - [Exocrine function of the pancreas and pathological histology of the stomach in patients with stomach yin deficiency syndrome (SYDS) research on SYDS following abdominal operation or with severe acute abdominal diseases (Part 3)]. AB - Exocrine function of pancreas (BT-PABA test) in 13 patients with SYDS was examined and gastric membrane in 5 cases with SYDS other than gastric diseases was observed under light- and electro-microscopy. The results were as follows: urine rate of recovery of PABA in SYDS was 35. 42 +/- 14.33% and that in the control with same age was 64.70 +/- 10.55%. The rate in SYDS was decreased obviously (P less than 0.001). Under light microscopy gastric mucosa of patients with SYDS showed slight gland degenerative atrophy, smaller cytoplasm, eosinophilic decrease of parietal cells and infiltration of inflammatory cells in interstitial tissue. Under electro-microscopy, the main changes of the gastric mucosa with SYDS were severe mitochondria damage, inflating rough endoplasmic pools and large vacuole at which membrane major particles of ribosomes disappeared, degenerated secretory vessels and formation of myelin figure in parietal cells, decrease of secretory particles in main cells, degeneration in some degree and decrease of nervous secretory particles in G cells and damaged interstitial capillaries. The results in this study suggested that the exocrine function of pancreas in patients with SYDS after abdominal operation or with severe acute abdominal diseases was decreased and there were some damages in energy supply and protein manufacturing systems of the gastric mucosa and functional disturbances of main cells, parietal cells and G cells in patients with SYDS. PMID- 2208435 TI - [Effects of gossypol acetate, progesterone, danazol and GnRH-A (gonadotropin release hormone-A) on the DNA-synthesis of human endometrial cell in vitro]. AB - Both aberrant endometrial cell and endometrial cell in situ, showed cyclic changes under the control of ovarian hormones. In this study, in order to observe a direct effect of medical therapy on the endometriosis, endometrial cells were cultured in vitro. Sensitivity test to 10(-6) M gossypol acetate, progesterone, danazol and GnRH-A were performed using determination of DNA synthesis by incorporation of tritiated thymidine. The results showed these drugs (but not GnRH-A) decreased the amount of attached cells, and lowered the DNA synthesis of endometrial cell in vitro (P less than 0.01). The inhibition rates of gossypol acetate was higher than that of progesterone and danazol, while that of progesterone was higher than that of danazol (P less than 0.01). The relationship between the growth inhibitory effect of progesterone and danazol showed a significant correlation for all points (r = 0.89, P less than 0.05). It has been suggested that some drugs might act a direct inhibitory effect on endometrial cell, such effect might be one of the modes in the treatment of endometriosis. GnRH-A had no direct suppression on endometrial cell in vitro, it has got clinical effect through the central effect at the hypothalamo-pituitary-ovary axis in treatment of endometriosis. PMID- 2208436 TI - [Treatment of childhood anorexin with spleen deficiency by principle of invigorating spleen and benefiting qi]. AB - 101 children of anorexia with Spleen deficiency were divided randomly into two groups, the invigorating Spleen(IS) group of 58 cases treated by modified Yi-Gong San, and the replenishing zinc(RZ) group of 43 cases treated by 0.2% zinc sulphate syrup. One course of treatment was 3 months. RESULTS: the clinical effects of IS group were notable in promoting appetite, increasing body weight and height, eliminating polyhidrosis, preventing common cold and tracheitis etc. The total effective rate was 96.6% in IS group which was significantly better than 72.1% in the RZ group (P less than 0.01). The effect of examination showed that the levels of hair zinc after treatment were markedly increased in both groups (P less than 0.01). The average increased value of hair zinc was 62.2 +/- 9.1 (ppm) in IS group which was higher than 42.1 +/- 7.2 (ppm) in RZ group (P less than 0.05). Moreover excretion rate and Hb after treatment in the IS group were markedly higher those in the RZ group (P less than 0.01). Chemical analysis showed that the concentration of zinc in modified Yi-Gong-San was very slight (0.73 mg/pack). It indicated that arising hair zinc in IS group was not simply supply of zinc but also the treatment in appetite, digestion and absorption, with which the body was supplied enough zinc naturally by food taken. PMID- 2208438 TI - [Duplication of animal model of ulcerative colitis and studies on rehabilitation effect of jianpiling prescription]. AB - In this paper, the ulcerative colitis model of rats with immuno-method was reported and the mechanism of using Jianpiling for the treatment of ulcerative colitis was studied. The rats of experimental group were subdivided into 3 subgroups (A, B and C), 15% Jianpiling suspension was given to rats in subgroup A per os, 15% Bupi-Yichang Pill to rats in subgroup B per os, 4.5% SASP suspension to rats in subgroup C, and same amount of saline to rats in the control group. The therapeutic results showed that the anti-diarrhia, anti-infection and repairing function of tissue by Jianpiling were obviously better than those of Bupi-Yichang Pill and SASP. Serological exams also showed that Jianpiling was much better than other therapeutic groups in increasing nonspecific cellular immunity and lowering level of antibody against large intestine and IgG. These results suggested that the mechanism of Jianpiling on ulcerative colitis was realized by increasing cellular immunity, inhibiting humoral immunity and promoting immune modulation. PMID- 2208437 TI - [Immunosuppressive effect of cultured Cordyceps sinensis on cellular immune response]. AB - The immunosuppressive effect of cultured Cordyceps sinensis (Bei Lin Capsule) was studied in vitro and in vivo. When the drug was added from 0.6 mg/ml to 5 mg/ml a significant dose-dependent inhibition effect was shown in the following immune reactions of mice (P less than 0.05-0.01): phagocytic function of peripheral blood leucocytes assayed by chemiluminescence; mitogenic response of spleen lymphocytes to Con A; mixed lymphocyte culture and LPS induced interleukin-1 release of macrophages. The survival rate of mice spleen lymphocytes cultured with Cordyceps sinensis 5 mg/ml in 37 degrees C 5% CO2 for 5 days was more than 80%. Cordyceps sinensis 4 g/kg daily significantly prolonged the mice skin allograft survival time (12.7 +/- 2.2 days v.s. 8.3 +/- 0.7 days in the control, P less than 0.01) and its immunosuppressive effect was close to that of Cyclosporin A 5 mg/kg daily on skin allograft. PMID- 2208439 TI - [Spontaneous dynamic qigong and mental disorders]. PMID- 2208440 TI - [Current status of research on the therapy of chronic kidney failure]. PMID- 2208441 TI - [Relation between kidney-deficiency, aging and free radicle-influence of tonifying kidney of free redicle]. PMID- 2208442 TI - Severe hypoxia activates lipid peroxidation in the rat brain. AB - The level of lipid peroxides, concentration of lactic acid in the blood and brain tissue homogenates were measured in rats under hypoxic hypoxia and hemorrhage. Significant correlation was found between the O2 supply-consumption ratio, the concentration of lactate and the level of lipid peroxides. It is suggested that the peroxidation process is activated by hypoxia. PMID- 2208443 TI - Phosphatidic acid affects structural organization of phosphatidylcholine liposomes. A study of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-(4 trimethylammonium-phenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) fluorescence decay using distributional analysis. AB - The fluorescence decay of 1-(4-trimethylammonium-phenyl)-6-phenyl-1,3,5 hexatriene (TMA-DPH) was used to study micro-heterogeneity of 1,2-dimyristoyl-3 sn-phosphatidylcholine (DMPC) liposomes and to characterize the effect of phosphatidic acid on the correlation between fluorescence microheterogeneity and membrane permeability. The fluorescence decay, measured using multifrequency phase fluorometry, has been analyzed either by using a model of discrete exponential components or a model of continuous distribution of lifetime values. Both analyses have shown that TMA-DPH decay is characterized by two components: a long one of about 9 ns and a short one of about 5 ns. In the gel phase, at variance with previous DPH studies, the short component was associated with a large fractional intensity. The distributional analysis showed changes of lifetime values and width in correspondence to the calorimetric transitions. The presence of egg phosphatidic acid increased both long lifetime values and distributional width. The use of TMA-DPH as a probe to evaluate membrane heterogeneity using the distributional width is discussed. The effect of phosphatidic acid on the membrane surface and in the hydrophobic core has been related to its structural properties and to its role in water penetration. PMID- 2208444 TI - Physical studies on the membranes and lipids of plasmalogen-deficient Megasphaera elsdenii. AB - Membrane fluidity and thermotropic phase behavior in the wild-type and plasmalogen-deficient strains of Megasphaera elsdenii have been studied by means of diphenylhexatiene steady state fluorescence anisotropy in isolated membranes, and by 31P-NMR and X-ray diffraction of the isolated phospholipids. Compared to the wild-type plasmalogen content of greater than 75%, plasmalogen-deficient strains had less than 5% plasmalogen, consisting largely of phosphatidylethanolamine and phosphatidylserine. Steady state fluorescence anisotropy measurements yielded an order parameter which was 6% lower in the plasmalogen-deficient membranes from 10 degrees to 40 degrees C, indicating higher membrane lipid mobilities. Both 31P-NMR and X-ray diffraction revealed the formation of a hexagonal phase in the lipids from the wild-type strain starting above 30 degrees C. In general the transition was not complete by 80 degrees C. In contrast, phospholipids from plasmalogen-deficient strains appeared to form a relatively stable lamellar phase. PMID- 2208445 TI - Hydrolysis of supported pyrenephospholipid monolayers by phospholipase A2. AB - Hydrolysis by pancreatic and snake venom (Crotalus atrox) phospholipase A2 of fluorescent monolayers of pyrene-labelled phosphatidylglycerol on solid support was studied. We used a fluorescence microscope equipped with video camera, video recorder and an image analyzer to monitor changes in fluorescence. Decrease in pyrene excimer emission was evident when pyrene phosphatidylglycerol monolayers transferred onto quartz glass slides (at a surface pressure of 15 mN m-1) were subjected to enzymatic hydrolysis. Snake venom phospholipase A2 could hydrolyze the monolayers almost completely while pancreatic phospholipase A2 could cause only 50% decrease in fluorescence intensity. EDTA totally inhibited the action of both A2 phospholipases. When monolayers were transferred onto solid supports at a surface pressure of 31 mN m-1 C. atrox phospholipase A2 could still exert activity whereas porcine pancreatic phospholipase A2 was inactive. PMID- 2208446 TI - [The geography of infection with the human immunodeficiency virus (HIV) in black Africa: determination of epidemiological and regional factors]. AB - In Africa, the continent most affected by HIV, the geography of the epidemic shows major contrasts. Strong regionalization differentiates both central-east Africa from west Africa and, within the countries, the urban zones from rural ones. Spatial and population factors are important when mapping the geography of the infection. An analysis of the evolution of movements--merchandise as well as populations--of the landlocked countries of the Great Lakes region of Africa leads the author to formulate a hypothesis involving regional considerations. PMID- 2208447 TI - [Carrier state for HBs antigen and HBc antibody in Brazzaville (congo): sero epidemiological study in the hospital and non-hospital environment]. AB - In Brazzaville (Congo), the prevalence of chronic carriage of HBs Ag (7.31%) we observed, is similar to the ones previously reported in 1981, 1982 and 1988. The sero-prevalence of anti-HBc is 67.21%. Anti-HBc are considered to be very relevant for the screening of VHB infection. Our study clearly points out that the highest prevalence of HBs Ag was observed among midwives. In all, the frequency distribution of the two serological markers we studied was similar in health workers and general population. PMID- 2208448 TI - [Cryptococcosis in Bujumbura, Burundi. Apropos of 80 observed cases in 42 months]. AB - Cryptococcosis is a systemic fungal disease and meningeal or meningoencephalitis involvement is the most serious complication. This is a retrospective analysis of 80 patients admitted from December 1983 to October 1985 (30 cases) and June 1987 to December 1988 (50 cases) in hospital of Bujumbura, Burundi, Central Africa. All patients have an AIDS. Clinically, the meningeal and meningoencephalitis attack prevails in 87% cases. The diagnosis in our study is essentially based on the examination of the CRL. Before the new antifungals, the treatment involved the association of amphotericin B and 5-fluorocytosine, during 6 to 8 weeks. This treatment was badly tolerated and the second falls, when the therapy was stopped, were frequent. Presently, the fluconazole is the best treatment of this affection (ailment?): it enables maintenance therapy for a disease in which the risks of recurrence and reinfection by the environment are not negligible in Africa. PMID- 2208449 TI - [Molecular probes in parasitology: perspectives in their application in the diagnosis of toxoplasmosis]. AB - After a brief recall on the difficulties of serological and parasitological diagnosis of acute forms of Toxoplasmosis, we present advantages of a new type of detection by highly reiterated genetic probes. Previous reports on genetic probes application in Mycology and Parasitology support our own research of toxoplasma diagnosis. PMID- 2208450 TI - [Epidemiology of malaria in French Guiana]. AB - A malaria investigation in the 1970-1986 period in French Guiana shows an increased plasmodium index (4.6%) when compared with the data of the 1970-1979 decade (2.7%), an incidence rate of 8.6 per 1,000 inhabitants (against 6.4 previously) and always a high frequency of P. falciparum (85%). The principal vector, A. darlingi, still remains sensitive to DDT but the authors recommend an updating of the anti-vectorial program control. A longitudinal serologic survey, on the school children during two years, shows the epidemiologic value of an immunological index. Its permits to precise the annual dynamic of malaria transmission and to distinguish in French Guiana three areas: a forest area with apparently permanent transmission, an hypo-endemic area with episodic transmission and a sporadic transmission area. PMID- 2208451 TI - [Assessment of a chloroquine-spiramycin combination in the treatment of malaria in an area of moderate resistance]. AB - The authors treated two groups of children in Zaire with two different regimens: chloroquine vs chloroquine-spiramycin. Chloroquine alone was successful in 83% of cases and chloroquine-spiramycin in 95% of cases (statistically significant). The tolerance of both regimens was excellent. PMID- 2208452 TI - [The cost of a campaign against malaria. General considerations]. AB - Malaria is yet one of the major tropical problems and the technical evolution of the malaria campaigns since 90 years is a witness of its complexity. The cost of a programme against malaria, including house spraying, case finding with chemotherapy and chemoprophylaxis for pregnant women, must allow a long-term (10 years) mobilization of resources. In Mayotte island (Comoro archipelago), the cost of the malaria campaign was, in 1987, about 6 US $ by inhabitant. Without man power cost, the house spraying needed 3 US $ by inhabitant, 0.2 US $ for Entomology and Parasitology Laboratories, 0.1 US $ for chemoprophylaxis, case finding and treatment. Apart from the frequency of house spraying which depends on epidemiological features (whole year or seasonal transmission), the integration of activities looks to be the major argument for the optimization of this cost. PMID- 2208453 TI - [Plasmodium falciparum drug resistance in the Congo. Evaluation of surveys carried out from 1985 to 1989]. AB - Surveys on drug sensitivity of Plasmodium falciparum carried out between 1985 and 1989 included 7-day in vitro tests and in vivo tests. 485 in vivo tests were carried out in eight surveys conducted in Brazzaville and in several inland regions. The subjects were congolese children aged between 3 months and 15 years old. They were recruited in hospital, mother-child clinics or at school. The drugs studied were chloroquine, amodiaquine and the sulfadoxine-pyrimethamine combination. 182 strains were tested in vitro in two surveys (December 1985 and January 1987); amino-4-quinolines, quinine and mefloquine were studied. Although resistance to amino-4-quinolines is a recent occurrence, by 1985 it had spread widely in the indigenous population in the Centre and South of the country. Resistance has since increased gradually, especially for chloroquine which undergoes specific surveillance. The situation is less serious in the North, a less densely populated region which is still enclosed. In an in vivo comparative study with chloroquine conducted in Brazzaville in November 1986, amodiaquine was found to be only slightly more effective at a similar dosage. At that time, certain isolated observations already seem to imply that the sulfadoxine pyrimethamine combination was also affected by resistance. This was not corroborated in an in vivo study carried out in 1989 on 40 children presenting with a malarial attack. Although the sensitivity to quinine may probably be decreased. This drug cannot yet be considered as being truly affected by resistance. The activity of mefloquine, the use of which is still limited, was satisfactory in 1987 in two different regions of the country. PMID- 2208454 TI - [Current findings on the epidemiology of alveolar echinococcosis in France]. AB - On the basis of a ten year study, the authors provide the present knowledge concerning the epidemiology of alveolar hydatid disease in France. The various hosts involved in the life-cycle of the parasite are enumerated. Six small rodent species act as natural intermediate hosts with marked differences in susceptibility. The definitive hosts are: i) wild foxes; 30 per cent of them are found parasitized in hyperendemic areas; ii) domestic carnivores especially dogs and to a lesser extent cats. Until the present work, the presence of infected domestic dogs and cats was not demonstrated in France. In conclusion, dogs seem to play an important role in the human contamination by the parasite. Consequently simple prophylactic measures are recommended. PMID- 2208455 TI - [Medical treatment of cysticercosis and monitoring of disease course using magnetic resonance imaging]. PMID- 2208456 TI - [Cysticercosis and neurocysticercosis: epidemiological survey in North Togo]. AB - An epidemiologic survey was carried out by a team of medical doctors working in the Kozah district of North Togo during April 1987. It was designed to evaluate the incidence of epilepsy and cysticercosis, taking a sample population of 5,264 subjects aged over 15 years old. 81.7% of the population feed on pigs which are allowed to roam freely in the vicinity of people's habitations. Cysticercosis (123 cases; incidence 23.3 cases per thousand) was diagnosed when one of the following three tests gave a positive result:--serum sample greater than or equal to 0.400 OD with ELISA test (101 cas),--identification of a cysticercosis cyst on anatomopathological examination of subcutaneous cysts (12 cases),--presence of typical calcification patterns revealed by cranial or muscle X-rays (21 cases in 18 patients). General epilepsy or partial motor fits were entirely clinically diagnosed (88 cases; 16 per thousand of population). Cysticercosis proved to be the cause of 29.5% epileptic sufferers, onset occurring after the age of 50 in 66% of these patients. PMID- 2208457 TI - [Circadian analysis of sleep, rectal temperature and immunological and endocrinological variables in sleeping sickness: preliminary study]. AB - A multidisciplinary study was conducted in 8 patients with neurological Human African Trypanosomiasis. The sleep-wake cycle followed an ultradian pattern which was more pronounced in patients with more severe symptoms. The EEG trace was consistently interrupted by numerous cyclic activation patterns with K complexes, rapid low amplitude elements and slow high voltage elements. Circadian rhythmicity was also disturbed in other physiological (rectal temperature), immunological (interleukins) or hormonal (cortisol, prolactin) variables, the disturbance being greater in severely hit patients. PMID- 2208458 TI - [Toxoplasmosis in the Republic of Senegal. Sero-epidemiological survey]. AB - The presence of Toxoplasmosis in Senegal was investigated by the detection of IgG antibodies. 415 samples were obtained from healthy subjects from different regions of the country. In subjects of over 30, a greater number were found positive for IgG antibodies if they lived in a humid climate (25% in Northern Senegal, 57.7% in eastern Senegal). In Dakar 33.3% of the pregnant women studied had antibodies. This study confirms the presence of Toxoplasmosis in Senegal. PMID- 2208459 TI - [Relapsing fever in Burundi. First case observed since 30 years]. PMID- 2208461 TI - [Study on the vertical transmission of the dengue virus in the South Pacific]. AB - In the course of a dengue outbreak, 765 larvae and 20 pupae were collected in Noumea and in Wallis island around patients premises, to investigate a possible natural infection. On 15 pools made of 335 Aedes aegypti larvae and pupae, 3 appeared to be infected. Dengue virus type 1 was the only serotype identified. Minimum infection rate reached 1: 112. In New Caledonia, the local strains of Aedes aegypti can insure the survival of dengue 1 virus between outbreaks, due to a vertical infection of their progeny. PMID- 2208460 TI - [2 cases of cysticercosis in Burundi]. PMID- 2208462 TI - [Cryptosporidiosis in acquired immunodeficiency syndrome. Apropos of the first Tunisian case]. PMID- 2208463 TI - [Development of chemoresistance of Plasmodium falciparum to chloroquine and mefloquine in Benin between 1980 and 1989]. AB - Resistance of P. falciparum to chloroquine has been notified in 1986 in non immune visitors. Authors organized surveys of in vivo and in vitro tests to follow evolution of the phenomena. The increase in number of P. falciparum strains resistant to chloroquine was sudden in 1986 but stopped to rise from this date, and even seemed to decrease gently. The geographical distribution of the resistance, restricted to the region of Cotonou, could be explained by illegitimate chloroquine distribution. But authors propose further investigations on relations between chloroquine resistant strains and the 3 anopheles species involved in malaria transmission in Benin. Resistance to mefloquine is rare in Cotonou region, but higher in rural zone. PMID- 2208464 TI - [Ecological factors in the renewed outbreak of malaria in Madagascar]. AB - The new epidemic of malaria which spread on the Madagascar high plateau in 1986 1987 is due to the combination of several factors (some of which are analysed by the authors, especially those related to anopheles, parasite and man). The authors compare the situations on the high Plateau and on St Mary Island, on the East Madagascar Coast, where the malaria is stable. Concerning the vector, the most interesting fact is the come-back of Anopheles funestus on the high Plateau from which it had disappeared at the beginning of the fifties. In this area, An.arabiensis seems to be the only representative of the gambiae complex whereas it is An. gambiae s.s. in St Mary Island. The parasite is getting more and more resistant to chloroquine. Nevertheless, man seems to develop protection, but it is difficult to analyse the markers which would prove the protection. However, that protection was assessed, on the humoral and cellular level, against the peptides of the RESA (Ring Infected Erythrocytes Surface Antigen), the circumsporozoite protein and the antigen E. PMID- 2208465 TI - [Toxoplasmosis in the Central African Republic. Complementary study in a rural area]. AB - The epidemiological survey on the incidence of toxoplasmosis in rural areas of Central African Republic was carried out on a healthy population. The 814 samples came from 5 regions with 4 different climates. About 40% of the adults had IgG antibodies against Toxoplasma gondii except in pre-desert area where only 25% were positive. Girls became positive earlier than boys, but there was no difference between adult men and women except in pre-desert zone where men were more positive. PMID- 2208466 TI - [Toxoplasmosis in the Congo Republic. Seroepidemiological study]. AB - Our study group, which was composed of over 2,500 subjects, aged between 0 and 65 years, came from different regions of Congo. The samples obtained were examined for the presence of IgG and IgM against Toxoplasma gondii. IgG were detected in about 33% of children over 9 years and in about 40% of adults. A study of IgM confirmed the early contact of children with the parasite (11% of positive samples for children between 4 and 9) and that of young women (5 to 7% positivity for subjects between 15 and 30). In spite of local variations, the extremely humid climate did not allow us to detect a difference based on the origin of the samples as furthermore there seems to be an ethnic factor involved. Among the different types of professions in our sample only farmers appear to be less frequently positive. Diet, as well as contact with animals do not seem to have an influence. PMID- 2208468 TI - [Trypanocidal activity and plasma kinetics of cis-Pt(II) pentamidine in the parasitized sheep]. AB - The trypanocidal activity of cis-Pt(II) pentamidine had been demonstrated during the first phase of Trypanosoma brucei brucei sheep experimental trypanosomiasis. But a subcutaneous treatment with 5 mg.kg-1 (+2 x 12 mg.kg-1) was not effective during the brain phase of trypanosomiasis. The blood pharmacokinetics of this compound had a plasmatic peak between 45 and 60 min, followed by a low decreasing phase along several days. The curve shape allowed an important interval before the following injection, and showed a compound storage in internal organs and extravascular sites. A model of cis-Pt(II) pentamidine metabolism had been studied: this product could be used as a chemoprophylactic medicine against African trypanosomiasis and American leishmaniasis. PMID- 2208467 TI - [Plasma kinetics of a spiroarsorane trypanocidal agent in sheep trypanosomiasis]. AB - In a previous study, spiroarsoranes were very effective against both the two pathogenic phases of the experimental sheep trypanosomiasis. In this paper, the authors had studied the plasmatic pharmacokinetics of these compounds. Data had shown one peak 10 min after injection of a 3 months inoculated sheep, and 90 min for the control sheep. Spiroarsorane had a good diffusion into the central nervous system, but the trypanocidal activity, during the second phase of the disease, was effective only after repeated treatment. The spiroarsorane low toxicity could allow its direction against nervous trypanosomiasis. PMID- 2208469 TI - [Agriculture-health interface in the field of epidemiology of vector-borne diseases and the control of vectors]. AB - This paper is a review of the interactions between agriculture and vector borne diseases. Rain forest clearing makes possible the development of heliophilous species of anophelines and snails leading to an increase of malaria and schistosomiasis in Africa. But in Asia, clearing is a control method against Anopheles balabacensis, an important malaria vector. Clearing of forest galleries is followed by the disappearance of shore-dwelling tsetse flies. Woodcutters and pioneer farmers are contaminated with arbovirus and leishmaniasis when entering in natural sylvatic foci of these diseases. Management of drinking water reduces guinea worm as well as cholera and other diarrhoeal diseases. More over when piped water becomes available people are no more obliged to store drinking water in containers where vectors use to breed. Reservoirs of dams offer large possibilities for the development of mosquitoes including anophelines vectors of malaria and filariasis and of snails hosts of schistosomiasis. The medical importance of these man-made breeding sites depends of the local epidemiological features of the diseases. Dam spillways provide breeding for blackflies and man made foci of onchocerciasis have been described in West Africa. Irrigation channels mainly when non cleared of vegetation are good breeding places for anophelines and snails. Irrigated surfaces like rice fields are highly productive in anophelines and other dangerous species of Culicinae. Insecticides used in agriculture, mainly to control cotton and rice pests, have been at the origin of insecticide resistance of several anopheline species. On an other hand, sometimes rice pests control lead to the control of rice field mosquitoes until they become resistant, e.g. for Culex tritaeniorhynchus the vector of Japanese encephalitis in South Korea. Many international organizations have emphasized the role of intersectorial collaboration to control man-made vector borne diseases foci. Good planning of the infrastructures (e.g. twin spillways) and adequate maintenance are essential. Vector control in rice field is a puzzling question. Wet irrigation was a hope but it cannot be done everywhere. Biological control methods have not been proven to be very efficient. Even Bacillus thuringiensis H14 and B. sphaericus have severe limitation. New tools for intersectorial activities should be a goal for scientists imagination. PMID- 2208470 TI - [The presence of Aedes (Stegomyia) albopictus in the Fiji Islands]. AB - An entomological survey conducted at the international airports of the Fiji Islands showed Aedes albopictus breeding in the protective area of Nadi airport. No Aedes aegypti nor Anopheles accidentally imported have been seen during the visit. Aedes vexans, A. pseudoscutellaris, A. burnetti, A. vigilax, Culex annulirostris, C. quinquefasciatus and a species of the pipiens complex have been collected incidentally out of airport areas. Due to the presence of Aedes albopictus, a new and important epidemiological risk must be considered now in Fiji Islands. Vector control measures must be taken urgently. These results demonstrate the necessity to maintain a strict vector surveillance in international airports. PMID- 2208471 TI - [Nanophthalmos with uveal effusion]. AB - A typical case of nanophthalmos with uveal effusion syndrome is reported. Clinical, pathological and therapeutic aspects of uveal effusion syndrome are discussed. A surgical treatment consisting of lamellar sclerectomies is proposed. PMID- 2208472 TI - [Transmission of visual fields by Minitel]. PMID- 2208474 TI - [Our experience with the Iogel implant. Apropos of 24 cases]. PMID- 2208473 TI - [Preoperative calculation of the power of lens implants by Donzis's formula. Apropos of 45 cases]. PMID- 2208475 TI - [Implantation of the sulcus in front of the occluded lens sac. Contribution to the prevention of secondary cataract. Apropos of 90 cases]. PMID- 2208476 TI - [Prevalence of bullous keratopathy in pseudophakia with indications for corneal graft from 1984 to 1988]. PMID- 2208478 TI - [Development of ocular tension after extracapsular and posterior chamber implant. Apropos of 215 cases]. PMID- 2208477 TI - [Pigmentary glaucoma following implantation of an artificial lens in the posterior chamber]. PMID- 2208479 TI - [Plicatures of the posterior capsule and the Bagolini effect]. PMID- 2208480 TI - [Prospective study of 115 cases of anterior chamber implants]. PMID- 2208481 TI - [Retinal detachment and pseudophakia. Personal experience and analysis of the literature]. PMID- 2208482 TI - [Retinal detachment in pseudophakia. Apropos of 35 cases]. PMID- 2208483 TI - [Artificial lens of Staar's type and intravitreous injection of gas: a strange phenomenon]. PMID- 2208484 TI - [Technics of explantation]. PMID- 2208485 TI - [Indications of explantation]. PMID- 2208486 TI - [Secondary implantation. Apropos of 26 cases]. PMID- 2208487 TI - [Surgical treatment of keratoconus by epikeratoplasty with fresh grafts]. PMID- 2208488 TI - [Correction of astigmatism and severe ametropia by epikeratophakia]. PMID- 2208489 TI - [Posterior scleral ectasis]. PMID- 2208490 TI - [Our experience with English botulinum toxin in the treatment of blepharospasm]. PMID- 2208492 TI - [Practical and theoretical aspects of the strabismic deviometry]. PMID- 2208491 TI - [The measurement theory and the example of the number zero]. AB - For basic research, measurement used in our medical routine doesn't seem to be self-evident. Classical physics claim and demand that everything should be measured with a maximum of exactness in order to avoid errors principly. Results of measurement and diagnosis are often regarded as on and the same thing. For quantum physics, measuring means rather description, approximation, and even perturbation due to manipulation. In strabismology, zero is the starting point of measurement and defines normality. The examination of 70 patients with asthenopia has reveiled that zero-localisation at the Maddox Wing doesn't imply parallelism of the eyes but an esophoria combined with an ocular-cervical syndrome. PMID- 2208493 TI - [Vertical and tortional deviations in early strabismus]. AB - The occlusion of one eye may trigger two types of deviation: 1) Heterophorias: the occluded eye deviates towards a horizontal, vertical or torsional abnormal position of rest. Fusion keeps the eyes straight during binocular fixation. 2) Dissociated deviations, horizontal (DHD), vertical (DVD), torsional (DTD): they are found in infantile strabismus. The deviation without fixation is always smaller than the deviation of the occluded eye. The more typical cases are the ones where the position of rest without fixation is an orthoposition. Normal binocular vision is lacking. Most of the time, an alternant neutralisation is found: the occlusion deviation is not the return of the occluded eye to an abnormal position of rest. The deviation is caused by a disequilibrium of binocular retinal stimulations. Horizontal and vertical deviations are easy to study. It is not the case in dissociated torsional deviation (DTD) where the incyclotorsion does not exist when fixation is absent. An indirect proof of extorsion is given by the study of horizontal and vertical deviations determined in the cardinal position of gaze. Extorsion of the globus leeds always to abnormal actions of the recti. This give a typical synoptometer chart which is found in any extorsion whatever its origins: paralysis, alphabetic patterns or infantile strabismus. Dissociated extorsions are always associated with a bilateral elevation in the primary position. Dissociated deviations are found in infantile strabismus with the other dissociations phenomenon such as nystagmus, optokinetic nystagmus asymmetry, fixation in adduction preference (and incyclotorsion). PMID- 2208494 TI - [Dissociated vertical divergence. Early strabismus. Nystagmus]. AB - The presence of a DVD makes the ocular motility examination complicate but it is a valuable sign for the clinician as it is noticed essentially in infantile early onset strabismus with latent nystagmus. It is fundamental not to confuse it with an hyperaction of the inferior oblique. It requires a surgical treatment: a recession of superior recti. PMID- 2208495 TI - [A new technic for recording eye movements by image processing. Principle and method]. AB - Nowadays, electro-oculography remains the only clinical method for ocular movement recording which is largely used in daily practise, but it has many drawbacks and limits. Till now the photo-oculographic technics have been only applied in laboratory conditions. A new differential photo-oculographic procedure is presented. This optical method is based upon the measurement of gaze direction and ocular movement amplitude from the relative pattern of five reflected corneal dots and pupil image which are located in two different optical plans. The authors relate in detail the recording devices and processing materials for the computerized analysis of video signals. The preliminary results confirm the real advantages of the method which allows to record all sorts of ocular movements in clinical conditions. PMID- 2208496 TI - [Comparative study of electrooculographic and photooculographic recordings]. AB - The authors present the results of clinical application of a new invasive real time method for ocular movement recording. There is an optical system which measures the gaze direction from the video signals of five reflected corneal dots and pupil image. Their study is based upon 110 simultaneous P.O.G. - E.O.G. recordings of normal beings or patients having various oculomotor troubles. It appears that the heavy odds of such a new method is obvious. It allows to obtain an absolute measurement of eye positions in relation to the basic line whatever the pattern and axis of the moving may be. A quantitative evaluation of all movement parameters is in progress. It still remains to solve the problem of large deviations and the wearing of optical correction during the examination. PMID- 2208497 TI - [Current etiological aspects of papilledema]. AB - Twenty-eight patients with papilloedema have been observed on twenty-thousand patients. In one third of the cases, they were associated with an hypertensive retinopathy. Another third was symptomatic of an expansive intra-cranial process. Otherwise, we only find a papilloedema in one case of eight with an expansive intra-cranial process. If a lot of them stay idiopathic and can regress without complication, it is necessary to look after them regularly, the secondary discovery of a cerebral tumor is not exceptional at all. PMID- 2208498 TI - [Early unilateral congenital cataract. Value of very early surgery]. PMID- 2208499 TI - [Preservation of human corneas in organ culture: technical protocol]. AB - Using organ-culture preservation human corneas were preserved up to 5 weeks in a modified tissue culture medium at 37 degrees C. The endothelial viability was examined after staining with trypan-blue 0.3%, after determination of endothelial cell density and cell loss and by light microscopy after staining with trypan blue 0.3% and alizarin red 1%. The biochemical analysis of the medium (pH, glucose, lactate) has allowed the evaluation of three kinds of storage. The influence of time preservation on the endothelial viability and the metabolic conditions are determined. At the end of this study a clinical trial is proposed. PMID- 2208500 TI - [Preservation of human corneas in organ culture: results of a feasibility clinical protocol]. AB - This study reports donor corneas stored at +37 degrees C in organ culture incubation. The follow up is 12 months. The graft survival is 92%. Two grafts are failed before 6 months. The mean control thickness is 0.54 mm and the mean endothelial cell density 1625 cells per mm2. A mean decrease in cell density of 40.6% is recorded. This study demonstrates that banked donor material can be successfully employed for corneal transplantation. PMID- 2208501 TI - [Retinal detachment and massive vitreoretinal proliferation: clinical study of 60 cases]. AB - Perfluoropropane gas as an adjunct to vitreoretinal microsurgery in the management of proliferative vitreoretinopathy. Pure perfluoropropane gas was used as an adjunct to vitreoretinal microsurgery in 60 eyes of 60 patients with rhegmatogenous retinal detachment complicated by proliferative vitreoretinopathy. 0.3 ml to 1.8 ml (average 0.9 ml) of pure perfluoropropane gas were used. The surgical procedure included a vitrectomy and a scleral buckling procedure in all patients. The follow-up after complete gas absorption ranges from 6 months to 3 years in the successful eyes. Total retinal reattachment was achieved in 41 eyes (68.3%). The anatomical success rate was 88% (22/25 eyes) in grade C1-C2 PVR cases, 68.7% (11/16 eyes) in grade C3-D1 PVR cases, and 42% (8/19 eyes) in grade D2-D3 PVR cases. Visual acuity of 0.1 or better was achieved in 80% of eyes with grade C PVR and 61% of eyes with grade D PVR. Visual acuity of 0.4 or better was achieved in 26.9% of eyes with grade C PVR. Macular changes were revealed by fluorescein angiography in 53% of successful eyes. We recommend the use of C3F8 rather than SF6 in the management of rhegmatogenous retinal detachment complicated by PVR. In our experience the anatomical success rate achieved with C3F8 is approximately the same as that achieved with SF6. However permanent retinal reattachment was achieved with a single operation in 87.8% of successful eyes of the present series of patients manages with C3F8 as compared to only 12% of successful eyes of a previous series of patients managed with SF6.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2208502 TI - [Value of contrast sensitivity in neuro-ophthalmology. Main indications]. AB - Contrast visual testing (CVT) is a psychovisual test newly used in the clinical study of neurovisual disorders. Using a micro E (Luer-Essilor) the authors present their technique and discuss the principal indications of CVT in neuro ophthalmology. PMID- 2208503 TI - [Refractive surgery and the non-freeze BKS set. Reliability of our Lyon methods. Value of our results]. AB - The authors analysed the results of 24 patients who underwent non-freeze refractive surgery with the BKS set. 22 myopic and 6 hypermetropic keratomileusis, and 6 epikeratoplasty are evaluated. The majority of patients had no astigmatism (or some irregular one) on corneoscopy. The final refraction may take up to 6 months to stabilize. The technique is difficult but may have application in the visual rehabilitation of these patients. PMID- 2208504 TI - [Primary empty sella turcica syndrome]. AB - Authors relate a typical case of primary empty sella turcica. Its physiopathogenesis is not yet well known, ophthalmological manifestations are non specific and variable, and authors point out difficulties in treatment. PMID- 2208505 TI - [Corneal complications caused by indomethacin eyedrop]. AB - During ocular treatments by drops of INDOCID are observed 4 superficial punctuate keratitis disappearing when INDOCID is discontinued, and 2 diffuse corneal oedemas. Some possible explanations for such a corneal involvement are suggested. PMID- 2208506 TI - [Prevention of graft rejection and disease recurrence with cyclosporin A in keratitis of Whitaker's syndrome]. PMID- 2208507 TI - [Contrast sensitivity and diabetes]. AB - Contrast sensitivity has been assessed in 24 diabetic patients in order to test the hypothesis that contrast sensitivity is impaired in the early stages of diabetes mellitus. All patients had 20/20 vision. Some evidence of visual dysfunction was observed in 33% of the diabetics with no retinopathy and 83% of the 6 patients with retinopathy when compared to 48 age-matched controls. Contrast sensitivity was mainly reduced in the mid-range spatial frequencies and correlated with the degree of retinopathy. The accurate assessment of visual dysfunction in diabetes is very important, as new drugs (i.e. aldose reductase inhibitors) are currently under evaluation. PMID- 2208508 TI - [A new test for evaluating functional vision and its application to "low vision"]. PMID- 2208509 TI - [A new simple instrument for ophthalmologic evaluation of patients with "low vision"]. AB - Authors present specially adapted visual acuity charts for "low vision" patients. For them refraction must be surveyed as often as possible. PMID- 2208510 TI - [Retinitis disclosing subacute sclerosing panencephalitis]. AB - SSPE is a panencephalitis who involves children and who leads to death. It is due to a defective measles virus. Ophthalmologic features are frequent and may be the first manifestation of the disease. The most typical ocular involvement is retinitis which can be misdiagnosed as a toxoplasmosis. PMID- 2208511 TI - [Leukoencephalopathy, calcifications of central grey nuclei, ophthalmologic manifestations following acute monoblastic leukemia treated with radiotherapy and methotrexate]. PMID- 2208512 TI - [Eye movements: initial dynamic approach in high resolution magnetic resonance imaging]. AB - New MR softwares allow a dynamic display of different fonctionnal anatomical regions. This work is a first attempt to visualize the ocular movements. A video tape constitute the support of our results. Technically, the work is performed on a Signa 1,5 T GE CGR System. During each MR acquisition, the subject is asked to fix his gaze successively on each spot of a scale set inside the bore of the magnet. Twenty four images are performed to show the entire lateral course of the globes. The examination time is about half an hour. The video display show the movements of agonist and antagonist muscles, the eyeballs and the optic nerves displacements, in the axial neuro-ocular plane (NOP). Different clinical applications of this new method are discussed (muscular surgery...). PMID- 2208513 TI - [Iridociliary melanoma with cataract (iridocyclochoroidectomy followed by extra capsular extraction with pseudophakia)]. AB - Description of a case of malignant melanoma of iris and ciliary body in a man of 59 years old. Clinically an interesting sign was the mahogany discolouration of the greyish cataract in the quadrant in front of the tumour. The tumour was removed following the technic of H.-S. STALLARD. Eighteen months later an E.C.C.E. was performed and a "Meur" model of implant inserted (optic in the post chamber and haptics in anterior chamber). Visual acuity in 1989 was 6/6 with glasses and a single binocular vision was recovered. PMID- 2208514 TI - [Reliability of linear corneal excisions using argon fluorine excimer]. PMID- 2208515 TI - [Radial keratotomies: peri- and early postoperative complications (apropos of 460 cases)]. PMID- 2208516 TI - [A rare iatrogenic effect of atropine eyedrops on the salivary glands]. AB - We have described a iatrogen effect of Atropine drops on salivary secretion. Pharmacology and iatrogen systemic effects are recalled; showing particularly the possible toxicity for the children in local use. PMID- 2208517 TI - [Quantification of visual field deficiencies using automatic perimetry in glaucoma. Preliminary note about a new method]. PMID- 2208518 TI - [Ocular hypertonia disclosed by the association of central retinal vein and cilioretinal artery occlusions]. PMID- 2208519 TI - [Retinal detachment in pseudophakic patients. Apropos of 39 cases]. AB - Pseudophakic Retinal Detachment (PRD) is of major concern, because since 1981, the number of patients receiving implants per year has been higher than that not implanted in the United States. Recently, the number of PRD has exceeded that of Aphakic Retinal Detachment (A.R.D.). This has been observed over the last two years in our unit. We report on 39 cases treated in the unit of Pr METGE between April 1986 and April 1988; P.R.D. characteristics, surgical procedures and anatomic results are presented. We have distinguished 4 types of P.R.D. Differences in prognosis may be imputed to the larger number of undetected tears and the more advanced vitreo-retinal proliferation in PRD as compared with A.R.D. Surgical procedures in PRD are identical with those of A.R.D., and implant may be maintained. Reinterventions, vitrectomy, and internal tamponnement are more frequently needed. The best prognosis observed in our patients occurred for PRD following ECCE + posterior chamber lens without peroperatory complications. PMID- 2208520 TI - [Endophthalmia of pseudophakic patients]. AB - After the era of antibiotics, a real improvement has been stated in the percentage of endophthalmis following cataract surgery which has fallen from 1% between 1950 and 1977, to 0.2-0.3% now. Since 10 lenses have been implanted, the incidence of acute bacterial endophthalmitis due to pathogenic organisms has not increased. But we now encounter many cases of "cold endophthalmitis", with a lowered symptomatology, a delayed onset, and which are due to organisms of low virulence. Their prognosis can be improved by early vitrectomy combined to intraocular antibiotics in the more severe cases, and by using antibiotics of high intraocular penetration in the milder cases. We report fifteen cases of pseudophakic endophthalmitis. The clinical course was acute in one case, sub acute in eleven cases, and chronic in three cases. In the latter fourteen cases a vitrectomy was performed in 60% of the cases. Aqueous and vitreous taps have found cocci gram + in five cases. Visual results are superior to 1/20 in 2/3 of the cases. PMID- 2208521 TI - [A case of post-traumatic occlusion of the central retinal artery]. AB - We report a case of central retinal artery occlusion following a minor ocular injury. The occlusions are an uncommon but well following some surgical operations on the eyeball, the eyelids or the nose. They probably result from an arterial spasm which trigger mechanisms are not very well known. PMID- 2208522 TI - [Pneumatic retinopexy. Apropos of 29 cases: our experience]. PMID- 2208523 TI - [Long-duration permanent wear]. PMID- 2208525 TI - [Anterior chamber cleavage syndromes]. AB - Authors analyse the anatomic findings in the anterior chamber cleavage syndrome and emphasize necessity of genetics (heredity being well known) and supervision for detecting glaucoma which occurs in about 50% of these patients and usually appears between 5 and 30 years of age. (Juvenile glaucoma). PMID- 2208524 TI - [Changes in the visual fields following filtering surgery in advanced glaucoma]. AB - The authors report about the results of a preliminary study concerning the changes of glaucomatous field after glaucoma filtering surgery in patients with advanced glaucoma. Mesopic campimetry had been selected because of its precision for central field defects. The first results appear to be favourable. No patient lost central vision suddenly after surgery. The authors have tried to research predictive risk factors. The factors that seem to be the most important to consider are the preoperative campimetric shape and the angle anatomy. PMID- 2208526 TI - [How to intubate the eye in severe glaucoma?]. AB - A new approach for the treatment of serious and/or uncurable glaucoma is proposed by the adjonction of a drain, cut in a crinotube, with micro-perforations and set in the classical opening of a trabeculectomy. In four years, for nine cases of particularly severe hypertonia, we observed one relative unsuccess, three real and stable improvements during two years and then with the necessity of local treatment (for rather young patients), and five clear and till today durable improvements. We have also observed a very good local tolerance for all cases, with never a persisting major hypotonia. This simple and efficient process seams susceptible to find its room in the treatment of severe hypertonia. PMID- 2208527 TI - Care not charted considered not done. PMID- 2208528 TI - Motivation for nursing research. PMID- 2208529 TI - Quality doctoral education in nursing with a Tennessee twist. PMID- 2208530 TI - Nitrous oxide 1844-1990. PMID- 2208531 TI - Epidural morphine for post-caesarean analgesia. PMID- 2208532 TI - Nitrous oxide does not exacerbate pulmonary hypertension or ventricular dysfunction in patients with mitral valvular disease. AB - Using the rapid-response thermistor pulmonary artery catheter and transoesophageal echocardiography, this study examined the effects of 100 per cent oxygen, 70 per cent nitrous oxide/30 per cent oxygen, and 70 per cent nitrogen/30 per cent oxygen on the pulmonary circulation and ventricular function in ten patients with pulmonary hypertension. In comparison with baseline measurements, nitrous oxide administration resulted in small but statistically significant (P less than 0.05) changes in mean arterial pressure (76 +/- 14 to 67 +/- 12), mean pulmonary arterial pressure (37 +/- 14 to 33 +/- 13 mmHg), and cardiac output (3.7 +/- 1.4 to 3.2 +/- 1.1 L.min-1). Seventy per cent nitrogen resulted in no significant changes from baseline. The repeat 100 per cent oxygen measurements were nearly identical to the nitrous oxide measurements. It is concluded that nitrous oxide does not exacerbate pulmonary hypertension or ventricular dysfunction during high-dose fentanyl anaesthesia in patients with mitral valvular disease. PMID- 2208533 TI - Epidural morphine for analgesia after caesarean section: a report of 4880 patients. AB - This retrospective study was undertaken to assess the efficacy and safety of epidural morphine in providing analgesia following Caesarean section under epidural anaesthesia. The morphine was administered as a single bolus, following delivery, in doses ranging from 2 to 5 mg. The charts of 4880 Caesarean sections, performed on 4500 patients, were reviewed. The duration of analgesia and the occurrence of any symptoms which might be side-effects of the epidural morphine were recorded. The duration of analgesia was 22.9 +/- 10.1 hr and was not correlated with the dose of epidural morphine. Eleven per cent of the patients required no supplemental analgesia during the first 48 hr. Twelve patients (0.25 per cent) had respiratory rates less than 10 breaths per minute, on at least one occasion. No serious sequelae resulted from these periods of bradypnoea. Pruritus occurred in 58 per cent of patients, nausea and vomiting in 39.9 per cent and dizziness in ten per cent. Herpes simplex labialis was recorded in 3.5 per cent of patients. Epidural morphine is thus confirmed as an effective analgesic technique post-Caesarean section with 3 mg being the optimal dose. Even in this young healthy patient population, clinically detectable respiratory depression occurs so clinical respiratory monitoring is indicated. PMID- 2208534 TI - Maternal awareness and neonatal outcome after ketamine induction of anaesthesia for Caesarean section. AB - Ketamine was used as the sole anaesthetic during the induction-to-delivery interval in 20 full-term patients undergoing elective Caesarean section. The intravenous administration of ketamine 1.5 mg.kg-1 was followed by succinylcholine 1.5 mg.kg-1 and tracheal intubation. The mother's lungs were then ventilated using 100 per cent oxygen until the baby was delivered. Intraoperative maternal awareness was assessed by the isolated forearm technique. The Apgar scores of the newborn at one and five minutes, as well as their umbilical vein blood gases were also evaluated and correlated with the induction-to-delivery (I D) and the uterine incision-to-delivery (U-D) intervals. In 13 patients (Group A) the I-D interval was less than 10 min and U-D interval less than 90 sec, while in seven (Group B) the I-D interval was greater than or equal to 10 min and the U-D interval greater than or equal to 90 sec. The isolated arm test was negative in all patients having an I-D interval less than 10 min, and was positive in three patients when the I-D interval exceeded ten minutes. The newborns of group A showed higher Apgar scores at one minute, as well as higher umbilical vein PO2 than was achieved in Group B. It was concluded that the technique used was not associated with maternal awareness or neonatal depression, provided that the I-D interval was less than 10 min and the U-D interval was less than 90 sec. PMID- 2208535 TI - Decreased glucose utilization during prolonged anaesthesia and surgery. AB - We studied the influence of prolonged anaesthesia and surgery on glucose metabolism by means of the euglycaemic insulin clamp method in eight patients who underwent prolonged surgery. Eleven patients who underwent surgery of short duration served as a control group. Plasma concentrations of catabolic hormones were measured simultaneously. Glucose utilization during prolonged anaesthesia, (PA) group, was lower than that in the control group (P less than 0.01) (glucose utilization 7.59 +/- 0.73 mg.kg-1.hr-1 in the control group vs 4.03 +/- 0.71 mg.kg-1.hr-1 in PA group respectively). There were no significant differences in plasma catecholamine and glucagon concentrations between the PA and control groups. Plasma-free fatty acid levels increased significantly in the PA group before the euglycaemic insulin clamp (free fatty acid level: 0.496 +/- 0.053 mmol.L-1 in the control group, vs 0.834 +/- 0.103 mmol.L-1 in the PA group at the pre-clamp period, P less than 0.01). Tissue resistance to exogenous insulin increased during prolonged anaesthesia and surgery although there were no significant changes in plasma catabolic hormone levels. PMID- 2208536 TI - Gastric fluid volume and pH in elective surgical patients: triple prophylaxis is not superior to ranitidine alone. AB - The effect of oral ranitidine alone was compared with sequentially administered ranitidine, metoclopramide, and sodium citrate on gastric fluid volume and pH in 196 healthy, elective surgical inpatients, each of whom was randomly assigned to one of four groups. Patients in all groups received oral ranitidine 150 mg 2-3 hr before the scheduled time of surgery. Those in Group 1 also received oral metoclopramide 10 mg one hour before surgery, and sodium citrate 0.3 M 30 ml on call to the operating room; Group 2 received sodium citrate but no metoclopramide; Group 3 received metoclopramide but no sodium citrate; Group 4 received ranitidine alone. Following induction of anaesthesia a #18 Salem sump tube was passed into the stomach and all available gastric fluid was aspirated. Volumes were recorded and pH measured. In all groups mean pH was greater than 5.8, although at least one patient in each group had pH less than 2.5. Mean volumes were significantly greater in patients who received citrate (Groups 1 and 2: 22 and 19 ml) than in those in those who did not (Groups 3 and 4: 10 and 8 ml). One patient in Group 2 and one in Group 3 had pH less than 2.5 with volume greater than 25 ml. Our results do not demonstrate any advantage of double or triple prophylaxis over ranitidine alone. The practical difficulty of correctly administering two or even three medications, each at different but exact preoperative intervals, is emphasized. PMID- 2208537 TI - Ethyl chloride and venepuncture pain: a comparison with intradermal lidocaine. AB - One hundred and twenty unpremedicated patients undergoing gynaecological surgery were randomly allocated to one of three equal treatment groups to assess the effectiveness of ethyl chloride in producing instant skin anaesthesia to prevent the pain of venepuncture from a 20 G cannula. They received either no anaesthetic, 0.2 ml one per cent lidocaine plain intradermally or a ten-second spray of ethyl chloride at the cannulation site. Ethyl chloride produced skin anaesthesia that significantly reduced the pain of venepuncture. However, it was not as effective as intradermal lidocaine. It had no effect on vein visualisation or ease of cannulation. Ethyl chloride can be recommended as a method of producing instant skin anaesthesia. PMID- 2208538 TI - Does forehead liquid crystal temperature accurately reflect "core" temperature? AB - Liquid crystal thermometry (LCT) is a non-invasive alternative to temperature monitoring. We evaluated the ability of forehead LCT, rectal temperature, and axillary skin temperature to trend distal oesophageal temperature during rapid warming on cardiopulmonary bypass. In 24 patients undergoing open heart surgery, temperatures were measured during the rapid warming phase on bypass (12-35 min). Scattergrams of temperature vs time for the four temperature sites each contained 150 data points. Polynomial regression analysis revealed that LCT, but not axillary or rectal temperatures, correlated with oesophageal temperature. We conclude that forehead LCT may be useful to monitor temperature trends and to detect rapid elevations in body temperature when more invasive temperature monitoring is inappropriate or unavailable. PMID- 2208540 TI - Transoesophageal pacing for perioperative control of neonatal paroxysmal supraventricular tachycardia. AB - The perioperative management of a 16-day-old infant with recurrent supraventricular tachycardia (SVT) is discussed. Vagal manoeuvres and medication were not adequate in controlling the SVT. Since the patient was scheduled for extensive surgery in the prone position, it was decided to use transoesophageal pacing as the method of choice for conversion of SVT. Transoesophageal pacing succeeded several times in overriding the SVT and restoring normal heart rate and haemodynamic variables. The advantages and disadvantages of various methods of treating SVT in the newborn are discussed. PMID- 2208541 TI - [An unusual anaphylactic reaction following succinylcholine chloride in a 21 month-old child]. AB - An anaphylactoid reaction occurring after the intravenous administration of succinylcholine in a 21-month-old child is reported. The clinical manifestations and signs were limited to the upper airways and eyelids. The child was not known to be allergic or atopic. The IgE level was normal. The search for specific anti choline IgE antibodies was negative. The skin tests were strongly positive for succinylcholine. The physiopathological and immunoallergic differences between anaphylaxis and anaphylactoid reaction are briefly discussed. PMID- 2208542 TI - Epidural analgesia for a parturient with herpes gestationis. AB - A 23-yr-old parturient with herpes gestationis spontaneously delivered a normal healthy infant under epidural analgesia. She received five injections of bupivacaine 0.5 per cent over a ten-hour period. There was no infection at the lumbar region, even though her body was covered with vesicles and bullae including the face and neck. Eight months after delivery the patient still has a vesicular eruption which occurs mainly during her menses. PMID- 2208539 TI - Brain protection: physiological and pharmacological considerations. Part I: The physiology of brain injury. AB - Ischaemia, whether focal or global in nature, produces a sequence of intracellular events leading to increased cell permeability to water and ions including Ca++. There is a loss of cellular integrity and function, with increased production of prostaglandins, free radicals, and acidosis with lactate accumulation. These events may be exacerbated by glucose administration. Pharmacological agents aimed at alleviating ischaemic injury could be directed at decreasing cerebral metabolic requirements for oxygen, improving flow to ischaemic areas, preventing Ca+(+)-induced injury, inhibition of free radical formation, lactate removal, inhibition of prostaglandin synthesis, and prevention of complement-mediated leukocyte aggregation. Part I of this paper describes some of the pathophysiological events leading to ischaemic brain injury. Part 2 of this paper will consider the current agents available for brain protection. PMID- 2208543 TI - Epidural anaesthesia for labour and caesarean section in a parturient with a single ventricle and transposition of the great arteries. AB - We describe a case of a 29-year-old parturient with a single ventricle and transposition of the great arteries who had lumbar epidural analgesia/anaesthesia with a local anaesthetic for labour, emergency Caesarean section and postoperative pain. Her outcome and that of her baby was successful. The anaesthetic techniques used in other parturients with similar congenital cardiac anomalies are reviewed. PMID- 2208544 TI - Beverly Charles Leech (1898-1960). PMID- 2208545 TI - The importance of calcium ions for in vitro malignant hyperthermia testing. AB - Intracellular Ca++ levels in skeletal muscle are elevated during the in vitro contracture response of muscle from subjects with malignant hyperthermia. The role of Ca++ in the bathing medium and the consequences of substitution of Sr++ for Ca++ in the response to agents associated with malignant hyperthermia were examined. When Ca++ was omitted from the bathing medium the contractures induced in human vastus lateralis by halothane (three per cent) or succinylcholine (50 mM) were reduced by 80 and 100 per cent, respectively, while contractures induced by caffeine (8 mM) were only reduced by 50 per cent. Substitution of Ca++ by another divalent cation, Sr++, completely restored contractures induced by caffeine, but only partially restored contractures induced by halothane or succinylcholine (to 50 and 30 per cent of Ca(++)-containing medium, respectively). Mepacrine (10 microM) was effective in antagonizing contractures by caffeine, whereas verapamil and nifedipine (10 microM) were not. These results support an essential role for extracellular Ca++ not fulfilled by Sr++ in contracture induction by halothane and succinylcholine, but not by caffeine. PMID- 2208547 TI - Continuous infusion interpleural analgesia for multiple fractured ribs. PMID- 2208548 TI - Failed intubation. PMID- 2208546 TI - Hospital admissions from the Surgical Day Care Centre of Vancouver General Hospital 1977-1987. AB - The admissions to Vancouver General Hospital from its Surgical Day Care Centre were reviewed for the period 1977 to 1987. The overall mean rate of admission for the period was 0.28 per cent, for surgically-related admissions 0.22 per cent and for anaesthesia-related admissions 0.07 per cent. The principal reasons for surgery-related admissions were postoperative bleeding, complications, the need for further surgery, the requirement for prolonged postoperative care, and pain. Urology had a particularly high percentage of admissions compared with its workload, because of the diagnostic nature of much of the work. Anaesthesia related admissions included "syncope," lack of an accompanying adult, aspiration pneumonitis and coincident acute disease. Twelve of the 14 patients admitted with syncope had surgery in the afternoon and had received less than ideal amounts of intravenous fluid. Seven of the 12 ASA physical status II patients admitted had an admission diagnosis related to the coincident disease. PMID- 2208549 TI - Breathing circuit occlusion due to defect in swivel port connector. PMID- 2208551 TI - Fatal embolism. PMID- 2208550 TI - Airway management in C-spine injuries. PMID- 2208552 TI - Prevention of obstruction of epidural catheter by blood clot. PMID- 2208553 TI - Epidural morphine injections for the treatment of postspinal headache. PMID- 2208554 TI - Subdural catheterization and opiate administration in a patient with Harrington rods. PMID- 2208555 TI - A WHO global programme for monitoring vector resistance to pesticides. AB - This paper describes the programme for monitoring vector resistance to pesticides and how it was established. It presents a summary of the computer baseline data and the cumulative number of vector species developing resistance at intervals of 5 years, starting in 1956, as well as information derived from Expert Committee reports dating back to 1947. The problems and concerns of the programme and envisaged solutions are also discussed. PMID- 2208556 TI - Transport and storage of vaccines in Hungary: the first cold chain monitor study in Europe. AB - With assistance from WHO the Hungarian Ministry of Health organized two cold chain studies: the first in three counties in summer (1 July to 30 September 1987), the second in six counties (including the previous three) in winter (1 January to 31 March 1988). The counties were chosen according to their distance (50-300 km) from Budapest, individual districts and child health centres being selected randomly. All participants were trained before beginning the studies. The vaccines (DPT, measles and BCG) for immunization, with attached cold chain monitors, were transported from the manufacturers to the child health centres using the normal distribution systems in the country. The whole cold chain process was analysed with regard to (1) actual exposures to adverse temperatures and delays in distribution; (2) the places where such exposure or delay occurred; (3) the percentage of vaccines at risk of deterioration (actual and predicted) at the end of the study; and (4) the performance of refrigerators of different types. Evaluation of the results (using WHO's EPIC software) showed significant deviations from acceptable standards. This first cold chain study in a European country proves that even in a temperate climate and with a reasonably well organized public health service there can be significant weaknesses in the transportation and storage of vaccines. Recommendations to overcome these deficiencies are given. PMID- 2208557 TI - Impact of measles vaccination on childhood mortality in rural Bangladesh. AB - This study examines the impact of measles vaccination on childhood mortality, based on longitudinal data from the Matlab maternal and child health/family planning programme in rural Bangladesh. It analyses the mortality experience of 8135 vaccinated and 8135 randomly matched nonvaccinated children aged 9-60 months, who were observed from March 1982 to October 1985. The results indicate that measles vaccination had a pronounced impact on both short- and long-term survival--the mortality rates for vaccinated children were as much as 46% less than those for nonvaccinated children. Immunization of children aged up to 3 years with measles vaccine appears to improve significantly their subsequent chances of survival. The findings underscore the need to give greater priority to measles vaccination within primary health care programmes in settings such as rural Bangladesh. PMID- 2208558 TI - The protective effect of the large-scale use of PHKC rabies vaccine in humans in China. AB - Reported are the results obtained with different immunization schedules of adjuvant or freeze-dried concentrated (FDC) primary hamster kidney cell (PHKC) rabies vaccine on volunteers. The FDC vaccine (potency, 4.5 IU), which was inoculated in six doses, on days 0, 3, 7, 14, 30 and 90, and the adjuvant vaccine (potency 2.5 IU), which was inoculated in five doses, on days 0 and 7 (double dose), 14, 30 and 90, induced earlier, higher, and more persistent neutralizing antibody titres than the adjuvant vaccine which was inoculated in five doses on days 0, 3, 7, 14 and 30. The persistence of the neutralizing antibody titres induced by three intradermal doses of vaccine administered on days 0 (4 sites), 7 (2 sites), and 28 (1 site) was lower than that induced by six intramuscular doses administered on days 0, 3, 7, 14, 30, and 90. A cell-mediated immunity (CMI) was also induced in vaccinees who received the adjuvant vaccine. The protective effect of the adjuvant vaccine was better than that of the previously used Semple vaccine and has had a positive effect on the epidemiology of human rabies in China. PMID- 2208560 TI - Bacterial infections in suspected cutaneous leishmaniasis lesions. AB - In Iran, microscopic examination of skin scrapings from 2202 individuals with clinically diagnosed cutaneous leishmaniasis (CL) lesions revealed the presence of amastigotes in 1123 cases (51.0%). Bacteriological examinations of the lesions indicated that 788 individuals (35.7%) were also infected with one or more pathogenic bacteria, including coagulase-positive staphylococci (27.8%), beta haemolytic streptococci (10.6%), and other opportunist pathogenic bacteria (total, 2.5%). The prevalence of bacterial infections in lesions in which leishmania parasites were detected was 26.5%, while for lesions in which no parasite was found the prevalence of such infections was significantly greater (45%). The results of this study show that bacterial infections should be considered in diagnosing and treating suspected CL lesions, particularly in areas where there is no facility for carrying out bacteriological examinations. Erythromycin can be used to treat the bacterial infections of the purulent sores. PMID- 2208559 TI - A case-control study of the impact of improved sanitation on diarrhoea morbidity in Lesotho. AB - A health impact evaluation of the Rural Sanitation Pilot Project in Mohale's Hoek district, Lesotho, was conducted from October 1987 to September 1988. A clinic based case-control design was used to investigate the impact of improved sanitation on diarrhoea morbidity in young children. The results indicate that under-5-year-olds from households with a latrine may experience 24% fewer episodes of diarrhoea than such children from households without a latrine (odds ratio = 0.76; 95% confidence interval, 0.58-1.01). The impact of latrines on diarrhoea was greater in those households that used more water, practised better personal hygiene, and where the mothers had a higher level of education or worked outside the home. In common with studies conducted in Malawi, Philippines, and Sri Lanka, little evidence was found that the relationship between latrine ownership and diarrhoea was confounded by socioeconomic status or environmental variables. For a sample of cases and controls, data on exposure status (presence or absence of a latrine) that were collected by interview at the clinics agreed closely with those obtained by observation during a home visit. PMID- 2208561 TI - An international survey of the educational activities of schools of nursing on psychoactive drugs. AB - A survey of the educational activities of schools of nursing on psychoactive drugs in 99 countries was carried out. All the schools that replied gave specific teaching and many also included the rational use of these drugs. The amount of time devoted to this teaching and the methods used varied greatly. Most schools felt that this topic needed more emphasis and many agreed that guidelines on teaching methods and approaches, as well as broad teaching aims and objectives, would be useful. PMID- 2208562 TI - Ascertainment of risk of serious adverse reactions associated with chemoprophylactic antimalarial drugs. AB - Serious adverse reactions during malaria chemoprophylaxis are reviewed. Three drugs considered to have caused serious reactions in recent years are pyrimethamine/sulfadoxine (Fansidar), pyrimethamine/dapsone (Maloprim) and amodiaquine. These reactions are principally independent of dose and cannot be determined during screening for optimal doses. However, host factors may precipitate dose-dependent reactions, some of which could be avoided with improvements in drug licensing. Since serious and life-threatening reactions are relatively rare (between 1:1000 and 1:20,000), Phase I to III trials cannot identify them. Reliance must therefore be placed on Phase IV post-marketing studies, including ongoing reviews of national registers, and specially tailored studies to identify the risk using prescription-event monitoring in high-risk populations. Occasionally, medical-record linkage, case-control and cohort studies may provide supportive data. Although large numbers of travellers must, of necessity, be exposed to a drug before relatively rare reactions are identified, the ascertainment of risk using post-marketing surveillance was prevented by the following five deficiencies: lack of awareness of early alerts, inadequate use of national registers, poor attention to epidemiological and statistical rigour, inadequate verification of denominators, and inadequacy of data records. Recommendations are given for minimizing such errors in the future. PMID- 2208564 TI - AIDS: recommendations for the interpretation of HIV-2 western blot results. PMID- 2208563 TI - Screening of average-risk individuals for colorectal cancer. WHO Collaborating Centre for the Prevention of Colorectal Cancer. AB - Recent developments in screening, diagnosis and treatment of colon cancer could lead to a reduction in mortality from this disease. Removal of adenomas, identification of risk factors, appropriate application of accurate diagnostic tests, and aggressive anatomic-surgical resection of colon cancers may already be having a favourable impact. Screening of average-risk populations over the age of 50 also offers promise in the control of this important cancer. The disease is of sufficient magnitude to deserve detection at an early stage with better prospects of patient survival, since screening tests with moderate sensitivity and high specificity are available. Flexible sigmoidoscopy and faecal occult blood tests are sufficiently acceptable to be included in case-finding among patients who are in the health care system. The results of current controlled trials involving more than 300,000 individuals for evaluating the impact of screening on mortality from colon cancer are needed before this approach can be recommended for general public health screening of the population. Further research is required to develop better screening tests, improve patient and physician compliance, and answer more definitively critical questions on cost-effectiveness. Mathematical modelling using current and new data can be used to determine the effectiveness of screening in conjunction with recommendations for primary prevention. PMID- 2208565 TI - The significance of biological heterogeneity. AB - Heterogeneity of expression for a variety of characteristics is found among malignant cells in the organism and in culture. Normal cells are relatively uniform when organized in a tissue, but become heterogeneous for many characteristics when they are dispersed and grown in monolayer culture. The heterogenizing effect of growth in culture indicates that the morphology and behavior of normal cells is ordered by their topological relations in tissues and other homeostatic influences of the organism. Weakening of these ordering relations may contribute to malignant transformation, as it usually does in rodent cell culture. Although phenotypic differences among cells of a given type may be transient, they can be perpetuated by protracted exposure to selective conditions. Examples are cited of selection which leads to an adapted state that is heritable for many cell generations after removal of the selective conditions. Such heritable adaptations are analogous to the Dauermodifikationen, or lingering changes, first described in ciliated protozoa and shown there to be under cytoplasmic control. The concept of progressive state selection is introduced to account for heritable adaptation at the cellular level. It depends on the spontaneous occurrence of transient, variant states and their successive selection to progressively higher levels of adaptation to an altered microenvironment. Although the process is basically epigenetic, it may be stabilized by genetic change. The concept is consistent with our present knowledge of tumor development, including progression to metastasis, and with epigenetic aspects of normal development. PMID- 2208567 TI - Chromosomal abnormalities in human breast cancer. AB - This review emphasizes cytogenetic changes and DNA analyses by Southern blot in primary breast tumors, rather than metastases, established cell lines, and pleural effusions. The data suggests that the most frequently altered chromosomes and chromosome regions are 1p, 1q, 2q, 3p, 5, 6q, 8p, 8q, 11p, 11q, 12, 13q, 14q, 16, 17p, and 17q. Changes on 8q, 11p, 11q, 13q, and 17q appear to be associated with either progression of the disease or poor prognosis. Alterations on 1p and 3p may represent early events in the development of breast cancer. PMID- 2208566 TI - Cellular interactions in metastasis. AB - The metastatic cascade is a sequence of events that must be completed for metastases to be established. The realization that tumors are heterogeneous, consisting of many different subpopulations differing in many characteristics, and the belief that there are selective events in the metastatic process have led several laboratories to isolate and characterize variants with both high and low metastatic potential. Typically, the highly metastatic variants have been able to form distant metastases when implanted into the subcutis. Such lines have been popular for studies of metastatic mechanisms and anti-metastatic therapy, but they may be atypical examples, and thus not the best experimental models. Recent studies indicate that normal tissue influences metastasis such that many tumors metastasize only if placed in the orthotopic site. Furthermore, some cells that do not metastasize individually are able to do so in conjunction with other variant subpopulations. Thus, mixtures of tumor cells in the tissue of origin can express a more malignant character. We review possible mechanisms for such influential interactions, as well as the role of cellular interactions in generating heterogeneity and stabilizing tumor characteristics. PMID- 2208568 TI - The invasive phenotypes. AB - The expression of the invasive (I+ or I-) phenotypes determines cancer metastasis (M+ or M- phenotype). The invasive (I+ or I-) phenotypes can be divided according to time and site of expression into subphenotypes, which can be assessed separately. At various sites along the metastatic pathway the expression of the I phenotypes can be accompanied by the presence of uncontrolled growth (G+ phenotype) or its absence (G- phenotype). Various combinations of the I and G phenotypes determine the behaviour of metazoan or parasitic cells under normal, pathological non-neoplastic and neoplastic conditions. Although the G+I+M+ combination correlates with full malignancy, the sequence of events leading to the acquisition of these phenotypes during tumor development is not clear. Conditional invasion in experimental systems indicates that a tumor may be invasive and metastatic when part of its population temporarily expresses the I+ phenotype. These experiments further stress the importance of the tumor-host ecosystem for the regulation of the I phenotypes. As distinct from some parasites, the invasive morphotype of vertebrate cells cannot be simply identified. Nevertheless, within the tumor-host ecosystem morphological correlates of the activities of invasive cells may be recognized. They reflect one or more of the I+ functions, namely: motility; loss of homotypic cell-cell adhesion; establishment of alternative cell-substrate and heterotypic cell-cell adhesion; breakdown of extracellular matrices. These functions are not exclusive for I+ tumor cells, and neither are the molecular markers investigated so far. Oncogene activation leads mainly to G+ expression, and in this way serves as a signal amplifier for the I and M phenotypes. Attractive candidate molecular markers of I phenotypes are: regulators of hydrolase activities; cell-cell adhesion molecules; cell surface receptors. From data presently available, we hypothesize that invasion depends upon the balance between and I+ and an I- pathway, with both pathways being sensitive to stimulation inhibition. PMID- 2208571 TI - Transformation injury and the unicellular phenotype of malignant cells. AB - In 1984, Philippe Shubik wrote in an editorial in the Journal of the National Cancer Institute that: 'In terms of general biology, the multicellular organisms have evolved a complex series of defensive responses to extracellular injury involving various inflammatory reactions and their systemic concomitants. Needless to say, these reactions are by no means always successful from the standpoint of the host and indeed may well be the immediate cause of the obvious ill effects noted. The unicellular organisms, in contrast, react to injury by dividing and moving. In the search for the features that may link chemical, physical, and viral carcinogens apart from their ability to induce neoplasia, only one characteristic in common is obvious, namely, their ability to produce intracellular change or injury while leaving the cell viable. Perhaps the initial and fundamental characteristics of neoplasia is a reversion of the cell to unicellular behavior. Division and invasiveness are the characteristics of the neoplastic cell, and increased motility certainly seems to be the most likely mechanism for invasion'. Dr. Shubik presented these views as a basis for 'further discussion' regarding the nature of the neoplastic response. We hope that this presentation will augment Shubik's plea by reviewing his idea in the context of our current knowledge of tumor development. In addition, we will attempt to integrate the concept of the unicellular behavior of tumor cells with Foulds' and subsequently Nowell's insightful hypothesis concerning tumor progression. PMID- 2208570 TI - Tumor vaccines. AB - Melanoma vaccines are an exciting and increasingly attractive immunotherapeutic approach for malignant melanoma. Vaccines can be used for patients with high risk primary melanoma and regional disease, stages in the progression of melanoma for which there is presently no treatment. They are unique in their potential to prevent cancer in high risk individuals. Multiple approaches are being followed to develop effective vaccines. It is too early to judge whether any of them effectively slow the progression of melanoma. However, it is clear that vaccines are safe to use, and that they can stimulate immune responses to melanoma in some patients. The specificity of these responses needs to be clarified, and multiple challenges remain to be overcome before effective vaccines to melanoma become available. We must first identify the antigens on melanoma that stimulate immune responses, define the immune effector mechanisms that are stimulated by vaccine immunization and identify those responsible for increasing resistance to tumor growth, devise appropriate ways of constructing vaccines that will induce such responses, and find adjuvants and/or immunodulators that will potentiate desirable immune responses. PMID- 2208569 TI - The current state of oncogenes and cancer: experimental approaches for analyzing oncogenetic events in human cancer. AB - The development of cancer is a multistage process. The activation of proto oncogenes and the inactivation of tumor suppressor genes play a critical role in the induction of tumors. Using human cell model systems of carcinogenesis, we have studied how oncogenes, tumor suppressor genes, and recessive cancer susceptibility genes participate in this multistep process. Normal human cells are resistant to the transforming potential of oncogenes, such as ras oncogenes, which are activated by specific point mutations. Since as many as 40% of some tumor types contain activated ras oncogenes, a preneoplastic transition in multistage carcinogenesis must involve changing from an oncogene-resistant stage to an oncogene-susceptible stage. The analysis of such critical steps in carcinogenesis using rodent systems has usually not represented the human disease with fidelity. In order to study this carcinogenic process, we have developed human cell, in vitro systems that represent some of the genetic changes that occur in cellular genes during human carcinogenesis. Using these systems, we have learned some of the functions of dominant activated-transforming oncogenes, tumor suppressor genes, and cellular immortalization genes and how they influence the carcinogenic process in human cells. Using our understanding of these processes, we are attempting to clone critical genes involved in the etiology of familial cancers. These investigations may help us to develop procedures that allow us to predict, in these cancer families, which individuals are at high risk for developing cancer. PMID- 2208573 TI - Serum kinetics of the anti-cancer agent 4-hydroxyandrostenedione in the rat. AB - A previously described radioimmunoassay (RIA) method for the measurement of 4 hydroxyandrostenedione (4-OHA) was used to investigate the serum drug levels attained after a single oral dose in male and female rats. Marked variability of serum drug concentrations and their time course were evident in male animals at all dose levels. In the female rat, in contrast, serum 4-OHA showed fewer individual differences, rose more rapidly and was sustained at substantially higher concentrations. In all animals, 4-OHA appeared in the serum within 0.5 h following the oral dose and persisted for at least 48 h. Doubling the dose from 8 mg/kg produced a disproportionately large elevation in serum drug levels, but a further increase to 32 mg/kg did not further increase serum levels. PMID- 2208572 TI - Effect of ribonucleotide reductase inhibitors on the growth of human colon carcinoma HT-29 cells in culture. AB - The effects of ribonucleotide reductase inhibitors on the growth of the human colon carcinoma cell line HT-29 were examined. Inhibitors were chosen for these studies that were specifically directed at each of the subunits of ribonucleotide reductase. The concentrations of drugs required to inhibit the growth of HT-29 cells by 50% (IC50) for hydroxyurea, 2,3-dihydro-lH-pyrazole-[2,3a]imidazole (IMPY), and 4-methyl-5-amino-l-formyl-isoquinoline thiosemicarbazone (MAIQ) were 206, 996, and 3.2 microM, respectively. Although the IC50 for deoxyadenosine alone was greater than 2,000 microM, in the presence of 5 microM erythro-9-(2 hydroxy-3-nonyl)adenine (EHNA), which protects deoxyadenosine from deamination by adenosine deaminase, it was reduced to 112 microM. The IC50 for deoxyguanosine was 1,060 microM. The addition of 8-aminoguanosine to protect deoxyguanosine from phosphorolysis by purine nucleoside phosphorylase did not increase the toxicity of deoxyguanosine in HT-29 cells. The combination of MAIQ or IMPY and deoxyadenosine/EHNA gave strong synergistic inhibition of HT-29 cell growth. The results of these studies indicate that ribonucleotide reductase inhibitors effectively block the growth of human colon carcinoma HT-29 cells and that combinations of inhibitors directed at the individual subunits of reductase result in synergistic inhibition of HT-29 cell growth in culture. PMID- 2208574 TI - Cytotoxicity and DNA damage caused by 4-demethoxydaunorubicin and its metabolite 4-demethoxy-13-hydroxydaunorubicin in human acute myeloid leukemia cells. AB - 4-Demethoxydaunorubicin (4-DMDR) and its major metabolite 4-demethoxy-13 hydroxydaunorubicin (4-DMDRol) were investigated for their cytotoxicity and mode of action against human leukemic cells. The drug and its metabolite appeared to be equally potent as both inhibitors of cell proliferation and inducers of DNA double-strand breaks in the OCI AML-3 cell line and cells derived directly from patients with acute myeloid leukemia (AML). This suggests that 4-DMDRol plays an important role in the antileukemic activity of 4-DMDR. PMID- 2208575 TI - A phase II trial of continuous-infusion 6-mercaptopurine for childhood solid tumors. AB - A phase II pediatric trial of a continuous intravenous infusion of 6 mercaptopurine (6-MP) in patients with refractory solid tumors or lymphoma was performed. The dosing schedule of 50 mg/m2 per hour for 48 h was chosen to produce optimal cytotoxic concentrations of 6-MP. There were no complete or partial responses in the 40 patients entered in the trial. Accrual was sufficient for the conclusion to be drawn that there was greater than 95% probability that the true response rate was no greater than 22% and 26% in osteosarcoma and Ewing's sarcoma, respectively. Dose-limiting toxicity was observed in one-third of the patients and included reversible hepatotoxicity, myelosuppression, and mucositis. The excellent penetration of drug into the cerebrospinal fluid (CSF) suggests that future trials of this intravenous dosing schedule should be conducted on tumors of the CNS. PMID- 2208577 TI - Clinical significance of monitoring serum levels of 5-fluorouracil by continuous infusion in patients with advanced colonic cancer. AB - Serum concentrations of 5-fluorouracil (5-FU) given by continuous infusion to 19 patients with advanced colonic cancer were measured by an HPLC method, and steady state concentration (SSc), area under the curve (AUC72) and total body clearance (Cl) were calculated as pharmacokinetic parameters. The serum level of 5-FU rapidly increased, reaching a plateau within 2 h after the start of administration. There were positive correlations between the dose and both SSc (r = 0.578, P less than 0.01) and AUC72 (r = 0.558, P less than 0.05). When the patients were divided into toxic and non-toxic groups according to the degree of toxicity, the values for SSc and AUC72 in the toxic group were significantly higher than those in non-toxic patients. The Cl value in the toxic group was also significantly different from that in the non-toxic group when data were calculated on a log scale. Furthermore, no differences in these parameters between effective and non-effective in these parameters between effective and non effective groups were detected when the patients were divided into two groups according to anti-neoplastic responses. These results indicate that increased serum concentration does not always provide therapeutic benefits to patients receiving continuous infusions of 5-FU. PMID- 2208578 TI - Pharmacokinetics of repeated i.v. bolus administration of high doses of r-met-Hu interleukin-2 in advanced cancer patients. AB - We studied the pharmacokinetics of recombinant methionyl human interleukin-2 alanine (r-met-Hu IL-2 [ala 125]) given at high doses by i.v. bolus according to Rosenberg's initial schedule in seven patients with advanced cancer. Serum concentrations of IL-2 were measured by radio-immunoassay. The drug followed second-order kinetics. During the administration of repeated high doses of IL-2, we noted a progressive increase in the volume of distribution (from 5,984 +/- 1,850 to 9,084 +/- 4,345 ml) and a progressive decrease in the AUC (from 32,643 +/- 3,817 to 22,397 +/- 511 IU min ml-1) and beta-half-life (from 61 +/- 14 to 48 +/- 6 min); the peak serum IL-2 concentrations also decreased significantly. We attribute these findings to an expansion of the extracellular fluid space and an increase in the number of IL-2 target cells during the treatment. PMID- 2208579 TI - Phase I toxicity and pharmacology study of trimethylcolchicinic acid in patients with advanced malignancies. AB - A phase I study of trimethylcolchicinic acid (TMCA) given orally once daily for 5 days every 3rd week was performed in 19 patients with advanced malignancies. Myelosuppression and mucositis were the major toxicities observed. Serum TMCA levels were monitored and appear to be useful in predicting toxicities. A partial response was seen in one lymphoma patient and stabilization of disease was noted in one patient each with prostatic and ovarian cancer. PMID- 2208576 TI - Implications and problems in analysing cytotoxic activity of hydroxyurea in combination with a potential inhibitor of ribonucleotide reductase. AB - The cytotoxicity of hydroxyurea in combination with 2.2'-bipyridyl-6 carbothioamide (a potential inhibitor of ribonucleotide reductase) on P388 murine leukemia is reported. Synergistic activity was studied using various interpretations of the isobologram method and the combination index method. We evaluated the pros and cons of these methods and their overall usefulness. In our opinion, to obtain all possible information from a compound association, it is important to choose a formally correct method that (a) can quantitatively evaluate synergism or antagonism, (b) may offer the possibility of averaging final results, (c) needs a minimal amount of experimental data, and (d) is rapid. Moreover, we emphasize both the utility of testing at least three molar ratios of compound association and the importance of carefully choosing the fractional inhibition used in calculating the combination effect. Such evaluation of drug combinations gives information essential to the preparation of new anticancer drug regimens and to the early assessment of biochemical interactions. PMID- 2208581 TI - Induction chemotherapy for newly diagnosed acute myeloid leukaemia using a regime containing cytosine arabinoside, daunorubicin and etoposide. AB - A total of 46 patients with previously untreated acute myeloid leukaemia were treated with an induction regimen consisting of 100 mg/m2 cytosine arabinoside given daily by 18-h i.v. infusion for 7 days, 50 mg/m2 daunorubicin given daily by i.v. bolus injection for 3 days and 75 mg/m2 etoposide given daily by 1-h i.v. infusion for 7 days. In all, 30 patients (67%) went into complete remission and were given further consolidation and maintenance chemotherapy. Of the 31 complete responders, 15 (48%) relapsed. The median disease-free survival of the 31 complete responders and the median overall survival of all 46 patients were 25 and 14 months, respectively. None of the clinical characteristics, which included sex, age, FAB morphology, extramedullary disease and initial WBC count, predicted the clinical response. Myelosuppression was the major toxicity and non haematological side effects were acceptable. The regimen appeared to have acceptable toxicity, and its efficacy was comparable with that of standard regimens. PMID- 2208580 TI - Phase I trial of indicine-N-oxide in children with leukemia and solid tumors: a Pediatric Oncology Group study. AB - A phase I trial of indicine-N-oxide was carried out in 12 children with solid tumors and in 16 with leukemia. Doses of 5, 6, and 7.5 g/m2 were given parenterally as a 15-min infusion every 3 weeks. The maximum tolerated dose in patients with solid tumors was 7.5 g/m2 and the dose-limiting toxicity was myelosuppression. In leukemia, the maximum tolerated dose was 6.0 g/m2 and hepatotoxicity was dose-limiting. Half of the children with leukemia showed elevations in transaminase levels and one child died of massive hepatic necrosis. This hepatotoxicity limits the use of indicine-N-oxide in children with leukemia. Antineoplastic activity was limited to a transient reduction in the numbers of circulating leukemic cells. PMID- 2208582 TI - Statin expression in the untreated and SarCNU-exposed human glioma cell line, SK MG-1. AB - Cytokinetic analyses of gliomas and other neoplasms rely exclusively on the use of proliferation-dependent markers such as [3H]-thymidine and BuDR incorporation and the detection of growth-dependent proteins such as proliferating cell nuclear antigen (PCNA) and Ki-67. In normal tissues, the monoclonal antibody S-44 recognizes statin, a nuclear protein expressed only in nonproliferating cells. In the present study, indirect immunofluorescence microscopy using S-44 identified nuclear statin in 5.9% of a population of untreated human SK-MG-1 glioma cells in vitro. Incremental doses of the alkylating agent sarcosinamide chloroethylnitrosourea (SarCNU) induced a linear increase in the fraction of statin-positive SK-MG-1 cells. Labeling of nuclear statin with the monoclonal antibody S-44 may be a potentially useful marker of the cytotoxic effects of anticancer drugs in gliomas and other neoplastic tissues. PMID- 2208583 TI - Development of monoclonal antibodies recognizing 7-(2-hydroxyethyl)guanine and imidazole ring-opened 7-(2-hydroxyethyl)guanine. AB - 7-(2-Hydroxyethyl)guanine (7HEG) is of biological interest because it is formed in vivo by reaction of DNA with ethylene oxide (EO). Furthermore, the major DNA adduct of vinyl chloride, 7-(2-oxyethyl)guanine, can be converted to this adduct by reduction. Two monoclonal antibodies (9E2, 4A5) recognizing 7HEG have been developed from BALB/c mice immunized with the adduct coupled to keyhole limpet hemocyanin. In addition, another antibody (8E10) was developed against the imidazole ring-opened form of the adduct (ro-7HEG). ELISAs were used to determine the sensitivity and specificity of these antibodies. With antibody 9E2, 50% inhibition of antibody binding in the competitive ELISA was at 54 pmol of the modified base 7HEG/well and 67 pmol 7HEGR/well, while with antibody 4A5, the values were 3.6 pmol 7HEG/well and 6.7 pmol 7HEGR/well. Antibody 8E10 gave 50% inhibition at 48 pmol ro-7HEGR/well. Neither antibody 9E2 nor 8E10 cross-reacted with unmodified DNA or with the normal nucleosides at the highest concentration tested. However, antibody 4A5 had a low affinity for deoxyguanosine (50% inhibition at 31,000 pmol). Sensitivity of adduct measurement can be increased 3- to 10-fold using an ELISA with fluorescence endpoint detection. These antibodies have been used to determine the level of adducts in DNA modified in vitro with [3H]- or [14C]EO. Because of the cross-reactivity of the most sensitive antibody, 4A5, with deoxyguanosine, a combined HPLC/immunoassay method was developed to quantitate 7HEG in DNA. The limit of sensitivity of this method is dependent upon the amount of DNA available for analysis. Using 30 fmol as the lowest detectable amount (20% inhibition) in the fluorescent ELISA with antibody 4A5 and 100 micrograms of DNA assayed per well, adduct levels of 1/10(7) nucleotide can be determined. This method was applied to DNA adduct detection in EO-treated myeloma cells and whole blood. Antibody 8E10 was also used in immunohistochemical studies to visualize ring-opened adducts in cells treated with EO followed by high pH. These antibodies will be used for the detection and quantitation of adducts in human samples. PMID- 2208584 TI - Differences in the modulation of P450IA1 and epoxide hydratase expression by benz[a]anthracene and 2,3,7,8-tetrachlorodibenzo-p-dioxin in mouse embryo versus mouse hepatoma-derived cell lines. AB - Polycyclic aromatic hydrocarbon (PAH)-induced C3H/10-T1/2/CL8 mouse embryo fibroblasts (10T1/2) and mouse hepatoma-derived Hepa 1c1c7 cells (Hepa-1), exhibit comparable total cytochrome P450 levels and total PAH-metabolizing activities but very different distributions of PAH metabolites. Based on anti P450IA1-IgG inhibition data, P450IA1 contributes essentially all PAH metabolism in Hepa-1 microsomes but is not involved in PAH metabolism by 10T1/2 cells. In addition, the microsomal epoxide hydratase (EHm) in Hepa-1 cells is far less effective in dihydrodiol (diol) formation compared to that in 10T1/2 microsomes [Pottenger, L.H. and Jefcoate, C.R. Carcinogenesis, 11, 321-327 (1990)]. In the present study, the levels of expression of P450IA1 and EHm proteins and the corresponding mRNAs, both prior to and following exposure to benz[a]anthracene (BA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), have been correlated with microsomal PAH metabolism by each cell type. In 10T1/2 cells, P450IA1 protein (56 kd) and mRNA (2.6 kb) were detectable at extremely low levels in only two of five cell preparations and then only after maximum induction by TCDD and BA. Thus although 10T1/2 cells contain functional Ah receptors, their capacity to induce P450IA1 is highly suppressed, representing at most 2% of the total P450. TCDD (10 nM) was 4-fold more effective than BA (10 microM) in inducing P450IA1 mRNA, while the levels of immunodetectable protein were comparable. An even greater discrepancy between P450IA1 mRNA and protein levels was seen in BA-induced Hepa-1 cells, where a 4-fold increase in mRNA was paralleled by a 20-fold increase in protein. This difference is probably due to the greater effect of BA depletion on mRNA compared to protein levels. In 10T1/2 cells, BA and TCDD were equally effective at increasing expression of an unidentified 1.9 kb mRNA sequence that blotted very weakly with the P450IA1 cDNA probe. The expression of this mRNA was independent from that of P450IA1. A similar band was visible in Hepa-1 cells less than 1% of the P450IA1 mRNA. EHm mRNA was almost 3-fold higher in 10T1/2 compared to Hepa-1 cells and was unaffected by cell treatments. In Hepa-1 cells, BA and TCDD elevated EHm protein and hydrating activity to levels comparable to those expressed in 10T1/2 cells. It is, therefore, suggested that the relative ineffectiveness of Hepa-1, compared to 10T1/2 EHm, to hydrate low levels of PAH epoxides is due to differences between the two proteins or their disposition in the microsomal membrane. PMID- 2208585 TI - Production of unsaturated carbonyl compounds during metabolism of hydroperoxy fatty acids by colonic homogenates. AB - Recent evidence has suggested that unsaturated carbonyl compounds may be the ultimate mitogens produced from the primary auto-oxidation products of unsaturated fatty acids. The present study has investigated the metabolism of 13 hydroperoxyoctadecandienoic acid (13-ROOH) by rat colon homogenates. This hydroperoxide is one of the primary products formed from the oxygenation of linoleic acid, the most abundant dietary polyunsaturated fatty acid. Incubation mixtures contained [1-14C]13-ROOH and colonic homogenates prepared from male Sprague-Dawley rats. After 30 min of incubation the reaction was quenched and the products extracted for analysis by HPLC. The identity of the eluted products were verified by UV, MS and NMR spectroscopy. The major products include a mixture of isomers of 2,4-dienone C18 fatty acids and 13-hydroxyoctadecadienoic acid. Direct comparison of homogenate metabolism to the hematin-catalyzed, alkoxyl radical mediated decomposition of 13-ROOH shows some significant differences. In particular, no epoxy products are detected in the presence of tissue homogenates whereas these are the major products observed during the decomposition of 13-ROOH by hematin and a number of other agents. These experiments demonstrate the production of relatively large amounts of unsaturated carbonyl-containing fatty acids during the metabolism of hydroperoxy fatty acids by colonic tissue. The major product, 13-oxo-9Z,11E-octadecadienoic acid, when instilled intrarectally stimulates the incorporation of [3H]deoxythymidine into colonic mucosal DNA, and induces colonic mucosal ornithine decarboxylase activity in vivo. These findings have important implications for the mechanism by which dietary fat promotes colon tumorigenesis as the formation of relatively reactive 2,4-dienones may be a key to the in vivo mitogenic activity of oxidized fatty acids. PMID- 2208586 TI - DNA adduct formation in target tissues of Sprague-Dawley rats, CD-1 mice and A/J mice following tumorigenic doses of 1-nitropyrene. AB - Recent reports have indicated that 1-nitropyrene is tumorigenic in laboratory animals. Since it is generally accepted that the covalent binding of carcinogens to DNA is causally related to tumorigenesis, we used 32P-postlabeling to examine the DNA adducts present in target tissues. 1-Nitropyrene (99.85-99.98% 1 nitropyrene, 0.15-0.02% 1,3-, 1,6- and 1,8-dinitropyrene by mass spectral analyses) was administered to Sprague-Dawley rats, CD-1 mice and A/J mice according to three tumorigenesis protocols. In DNA obtained from the injection site of Sprague-Dawley rats, two major adducts were observed. Based upon their chromatographic behavior and sensitivities to treatment with nuclease P1 and hydrazine, these adducts were identified as N-(deoxyguanosin-8-yl)-1-aminopyrene (dG-C8-AP) and N-(deoxyguanosin-8-yl)-1-amino-3-, 6- and/or 8-nitropyrene (dG-C8 ANP), which are adducts derived from the nitroreduction of 1-nitropyrene and dinitropyrenes respectively. In mammary gland DNA from Sprague-Dawley rats, two adducts were found. One of these had chromatographic characteristics and hydrazine and nuclease P1 sensitivities similar to dG-C8-AP, while the identity of the other adduct is presently unknown. The only DNA adduct detected in the livers of newborn CD-1 mice and the lungs of A/J mice was dG-C8-ANP. The presence of dG-C8-AP in the injection site and mammary gland of the Sprague-Dawley rats indicates that nitroreduction is involved in the metabolic activation of 1 nitropyrene in these tissues. Since an unidentified adduct was also found in the mammary gland, other pathways are important in this tissue. The presence of only dinitropyrene DNA adducts in the livers of CD-1 mice and lungs of A/J mice indicates that dinitropyrenes are activated very efficiently to electrophilic metabolites, to an extent far better than 1-nitropyrene. PMID- 2208587 TI - Comparative tumorigenicity of picene and dibenz[a,h]anthracene in the mouse. AB - The carcinogenic activity of the two polycyclic aromatic hydrocarbons (PAHs), picene (benzo[a]chrysene) and dibenz[a,h]anthracene (DBA), was determined in NMRI mice by five different experimental protocols in order to find out if picene is a carcinogen as predicted by recent quantum mechanical calculations in contrast to earlier observations which could not confirm any carcinogenic activity of picene. Single s.c. treatment of adult mice with picene or DBA (308 nmol/animal, each) led to the formation of fibrosarcomas in 63.3% of treated animals regardless of the PAH used. Chronic epicutaneous application of both PAHs (total dose 1.36 mumol) to the back of mice resulted in the development of papillomas with a tumor rate of 22% in the case of picene and of 32% in the case of DBA. When newborn mice were s.c. treated once on day 2 of their life with each of the two PAHs (400 nmol/animal), 27.8% of treated animals developed lung adenomas after 40 weeks in the case of picene compared to 92.1% in the case of DBA. Histopathological examination of the tumors in the three experimental models revealed no difference in the type of tumor between picene and DBA. Epicutaneous application of both PAHs (600 nmol/animal) followed by chronic treatment with 12-O-tetradecanoyl phorbol-13-acetate for 24 weeks led to the formation of papillomas in 93% of animals treated with DBA while picene showed no tumorigenic activity at all. Initiation of tumorigenesis in the two-stage tumor model with 7,12 dimethylbenz[a]anthracene (1 mumol/animal) and chronic treatment with picene (total dose 4.8 mumol) for 24 weeks was equally ineffective in producing tumors in NMRI mice. This rare biological property of picene, which is a complete carcinogen, yet at most a very weak tumor initiator, is explained in terms of its inefficient biotransformation to mutagenic and carcinogenic metabolites as compared to the strong tumor initiator DBA. PMID- 2208588 TI - Evidence for spontaneous conversion of Mex- to Mex+ in human lymphoblastoid cells. AB - A series of human lymphoblastoid cell lines (LCLs) called Mex- were defined by Sklar and Strauss on the basis of their inability to remove O6-methylguanine from DNA. Instability of Mex- has previously been shown as a population phenotype of LCLs. We examined whether Mex- as a cellular phenotype is spontaneously convertible or not. At the population doubling number (PDN) 23 after recloning, two out of 15 independent subcultures derived from a Mex- LCL, AT1-1, were found to contain a small fraction of Mex+ cells after treatment with 1-(4-amino-2 methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU). Three Mex+ subclones were identified without exposure to ACNU among 486 subclones from replica plating of an expanded Mex- clone (PDN30). The rate of spontaneous conversion was estimated to be in the range of 10(-8)-10(-7) per cell per generation by the fluctuation analyses on two Mex- subclones. These results strongly support the hypothesis that Mex- as a cellular phenotype is spontaneously convertible to Mex+. PMID- 2208589 TI - DNA adenine adducts induced by nitrogen mustards and their role in transcription termination in vitro. AB - Previous studies have demonstrated that three cancer chemotherapeutic compounds of the nitrogen mustard class, melphalan (L-PAM), nitrogen mustard (HN2) and chlorambucil (CBC), each generated DNA lesions that prematurely terminate in vitro transcription. Sites of these lesions were inconsistent with sites of N7 guanine monoadducts formed by these compounds, and in the cases of L-PAM and CBC were suggestive of adenine lesions. The present study is an attempt to identify and characterize nitrogen mustard-induced non-N7 guanine DNA adducts, and in particular adenine DNA adducts, and to assess their role in drug-induced in vitro transcription termination. Data from studies using a modified Maxam-Gilbert DNA sequencing technique demonstrate that L-PAM and CBC, but not HN2, generate heat labile, alkaline-stabilized adenine adducts at nearly every adenine in a region of a defined DNA template examined. Comparison of sites of L-PAM- and CBC-induced adenine adducts to known sites of drug-induced transcription termination in the same DNA template show that L-PAM- and CBC-induced transcription termination is associated not with drug lesions at single adenines, but rather with drug-induced adducts at neighboring adenines. Additional in vitro transcription studies using a small DNA molecule generated by polymerase chain reaction-mediated DNA amplification demonstrate that none of the transcription-terminating lesions induced by L-PAM and CBC in this molecule are interstrand in nature. These results suggest that some, but not all, nitrogen mustard compounds can generate heat-labile adenine lesions in DNA, and that bifunctional nitrogen mustards that can form heat-labile adenine adducts also form adducts consistent with intrastrand adenine-adenine crosslinks. These adducts at pairs of adenines in turn appear to be responsible for L-PAM- and CBC-induced transcription termination in vitro. PMID- 2208590 TI - The determination of urinary 3-methyladenine by immunoaffinity chromatography monoclonal antibody-based ELISA: use in human biomonitoring studies. AB - A mouse monoclonal antibody (Mab) was prepared which showed high specificity for a potential marker of exposure to methylating carcinogens such as 3-methyladenine (3-MeAde). In a low-temperature (4 degrees C) ELISA a linear calibration curve was obtained between 3 and 50 fmol/well. In combination with an immunoaffinity (IA) column prepared from a 3-MeAde rabbit antiserum, the ELISA was used to determine 3-MeAde in urine. The IA-ELISA method was validated by comparison with results obtained by an IA-GC-MS method. The effect of consuming a low 3-MeAde diet on urinary 3-MeAde excretion was investigated in a human volunteer. Urine collected during a 'normal' diet exhibited the characteristic variation in 3 MeAde levels previously observed (9.5 micrograms/24 h, SD = 4.4, n = 5). In contrast, 3-MeAde excretion was markedly lower and less variable on days when the diet was closely controlled (0.63 microgram/24 h, SD = 0.08, n = 3). Dietary intake of 3-MeAde on the latter days was between 0.37 and 0.43 microgram/day, indicating that most, if not all, of the 3-MeAde seen in previous experiments was derived from the diet. The origin of dietary 3-MeAde is not known, but may be related to fumigant use. Dietary manipulation affords the possibility of carrying out model studies, in volunteers, on 3-MeAde intake and formation in vivo. PMID- 2208591 TI - Monoclonal antibodies for the specific detection of 3-alkyladenines in nucleic acids and body fluids. AB - We describe an immunoanalytical procedure for the detection and quantitation of 3 alkyladenines in biological samples with the use of anti-(3-alkyladenine) monoclonal antibodies (Mab). A new hapten-protein conjugate, 3-ethyl-8-(3 carboxypropyl)-adenine, was used for immunization of BALB/c mice after conjugation to carrier proteins via the carboxyl group. Eighty-nine hybridomas were established which secrete anti-(3-alkyladenine) Mab with antibody affinity constants ranging from 1 x 10(7) to 5 x 10(9) l/mol for 3-ethyladenine (3-EtAde). One of these Mab (EM-6-47) had detection limits of 30 fmol for 3-EtAde, 17 fmol for 3-n-butyladenine (3-BuAde) and 475 fmol for 3-methyladenine (3-MeAde) respectively, at 25% inhibition of tracer-antibody binding. The binding pattern of Mab EM-6-47 revealed high specificity for adenine substituted at N-3 with different alkyl residues and no, or very low, cross-reactivity with other alkylated or unmodified nucleic acid components or structurally related compounds. 3-MeAde and 3-EtAde can be well separated from nucleic acids, and from rat and human urine samples, using HPLC with two successive stationary phases. Using Mab EM-6-47 in conjunction with a competitive RIA, both 3-MeAde and 3-EtAde were detected in the range of 100-300 ng (3-MeAde) and 2-10 ng (3-EtAde) in urine samples (10 +/- 2 ml) of untreated rats collected over a 24 h period. Only 3 MeAde (range 1.3-24.20 micrograms) was found in human urine samples. The concentration of 3-EtAde in rat urine increased significantly during the 24 h following a single i.v. application of N-ethyl-N-nitrosourea. After i.p. application of known amounts of 3-MeAde and 3-EtAde, greater than 90% of 3-MeAde and greater than 70% of 3-EtAde were excreted in rat urine within the subsequent 24 h. The concentration of 3-alkyladenines in body fluids (urine) may thus provide a useful indicator of environmental exposure to nucleic acid-reactive agents, and the immunoanalytical procedure described here permits the sensitive determination of adenines carrying different substituents at N-3. PMID- 2208592 TI - Peroxidase-mediated reaction of the carcinogenic non-aminoazo dye 1-phenylazo-2 hydroxynaphthalene with transfer ribonucleic acid. AB - Horseradish peroxidase in the presence of hydrogen peroxide has the ability to mediate the activation of carcinogenic 1-phenylazo-2-hydroxynaphthalene (Sudan I) to DNA- and transfer RNA (tRNA)-bound products in vitro. tRNA is more accessible for modification by the activated carcinogen studied. tRNA modified by activated Sudan I becomes colored and has an absorption maximum of approximately 480 nm. Binding of metabolite(s) to tRNA is inhibited by ascorbate, glutathione, Mg2+ ions and nitrosobenzene. The mechanism of these protections was shown to be different for the different agents. tRNA modified by activated Sudan I exhibits a significantly increased acceptance for L-methionine. Enzymatic hydrolysis of modified tRNA with subsequent separation of nucleosides by HPLC suggests that the covalent modification of tRNA originating from the formation of more than one adduct with the nucleosides in tRNA is the predominant interaction of the activated Sudan I with tRNA. PMID- 2208593 TI - Introduction of the activated N-ras oncogene into human fibroblasts by retroviral vector induces morphological transformation and tumorigenicity. AB - The introduction of activated N-ras cDNA into normal diploid human skin fibroblast cell cultures using the retroviral vector pZIPneo results in a spectrum of morphologies ranging from near normal to, in rare instances, dense piled-up colonies of morphologically transformed cells. However, none of the clones isolated were transformed as assessed by growth on agar or tumorigenicity in nude mice. Introduction of both c-myc and N-ras oncogene cDNAs into normal skin fibroblasts failed to produce transformation as assessed by growth on agar and tumorigenicity in nude mice, although c-myc infection alone conferred immortality and the resultant doubly infected cell line was immortal. Using the same construct, activated N-ras cDNA was shown to transform immortalized human fibroblasts to tumorigenicity. However, immortalization per se was shown not to guarantee 'co-operation' with an activated N-ras gene to give malignant transformation. Although numerical and structural chromosome aberrations (clonal and non-clonal) were observed in some of the cell strains isolated after retroviral infection, these were not directly associated with viral infection, the presence of the oncogenes or with the morphologically transformed phenotype. PMID- 2208594 TI - Response of the ke test to NCI/NTP-screened chemicals. I. Non-genotoxic carcinogens and genotoxic non-carcinogens. AB - The response of a physico-chemical carcinogen-screening test, the k(e) test, to 46 rodent carcinogens and 20 putative non-carcinogens that had been screened in long-term two-species bioassays by the National Cancer Institute/National Toxicology Program are reported. All of the chemicals screened are those that yield mutagenicity responses in the Ames Salmonella/microsome test that are either equivocal or contrary to the rodent carcinogenicity responses. The electron attachment rate constants, k(e)S, of the test chemicals in cyclohexane at 21 degrees C were measured using a pulse-conductivity technique. The k(e)S of 27 of the 46 rodent carcinogens (59%) are equal or greater than the diffusion controlled k(e) of carbon tetrachloride, which is regarded as the boundary between a positive and negative response; the k(e)S of 8 of the 20 mutagenic non carcinogens (40%) are less than diffusion-controlled. If the boundary between positive and negative k(e) responses is decreased to half the diffusion controlled k(e), six additional carcinogens yield a positive ke response which increases the k(e) test sensitivity to 72% while the specificity to non carcinogens remains at 40%. Comparison of these k(e)S with measures of the chemicals' electrophilicity that had been inferred from chemical structure indicates that k(e) provides a markedly different measure of electrophilicity and one that complements the Ames Salmonella assay. The use of the k(e) test as an analytical tool to indicate the presence of electron-attaching impurities in solvents such as benzene is discussed, as is the sensitivity of the k(e) test to rodent-liver carcinogens. PMID- 2208595 TI - Characterization of a glucuronide metabolite of 4-(methyl-nitrosamino)-1-(3 pyridyl)-1-butanone (NNK) and its dose-dependent excretion in the urine of mice and rats. AB - Following analysis by reversed-phase HPLC, a previously uncharacterized metabolite of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was found in the urine of A/J mice treated with NNK. Treatment with beta-glucuronidase converted the metabolite to a peak that co-eluted with 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanol (NNAL). Treatment with sulfatase or beta-glucuronidase plus saccharic acid 1,4-lactone did not change the retention time of the metabolite. These data suggested that the unknown metabolite was a glucuronic acid conjugate of NNAL. Upon isolation and purification of larger quantities of the metabolite from the urine of A/J mice, CD-1 mice and F344 rats, 1H and 13C NMR and MS confirmed that the unknown metabolite was 4-(methylnitrosamino)-1-(3-pyridyl)-1 butyl beta-D-glucopyranosiduronic acid (NNAL Glu). To determine the quantitative relationship between NNK dose and NNAL Glu production and to compare the importance of glucuronidation relative to other metabolic pathways, [5-3H]NNK was administered to F344 rats and A/J mice at doses of 500-0.005 mumol/kg. At 500 mumol/kg, NNAL Glu accounted for 22% of the total urinary excretion of NNK in A/J mice, and for 8% in F344 rats 48 h after dosing. The proportions of excreted glucuronide and NNAL decreased with diminishing doses of NNK, yielding undetectable levels of each metabolite in both mice and rats at a dose of 0.005 mumol/kg NNK. Since substantial amounts of metabolites formed via alpha hydroxylation and N-oxidation pathways were observed at the lower doses of NNK, these data demonstrate that NNAL glucuronidation is a quantitatively unimportant metabolic pathway at low doses of NNK. PMID- 2208596 TI - Peroxyl radical-dependent epoxidation of cyclopenteno[c,d]pyrene. AB - We have reported previously that cyclopenteno[c,d]pyrene (CPP), an environmentally prevalent polycyclic aromatic hydrocarbon, is activated as a bacterial mutagen by several model systems which generate peroxyl radicals. In this report we present our findings on the chemical fate of CPP in these activating systems. The peroxyl radical systems employed are microsomal prostaglandin H synthase and arachidonic acid, the hematin-catalyzed decomposition of a lipid hydroperoxide, and the autoxidation of the sulfite anion. Reverse-phase HPLC analysis of stable products of CPP metabolism yielded qualitatively identical profiles from the first two systems. The three major products from these systems were analyzed by UV/visible and fluorescence spectroscopy, and a mass spectrum was obtained for the most abundant product. Based on these spectral analyses and on chromatographic behavior, the three products were identified as the cis- and trans-isomers of 3,4-dihydroxy-3,4 dihydro-CPP and 4-keto-(3H)-CPP. The identities of these products and their quantitative distributions relative to the epoxide hydrolase activities present in the microsomal system and the hematin system clearly establish 3,4-epoxy-CPP as the key intermediate and probable active mutagen generated in the peroxyl radical-dependent metabolism of CPP. This epoxidation of the activated aliphatic double bond of CPP extends the known range of peroxyl radical-dependent oxygenations by demonstrating the direct, one-step activation of a carcinogenic, environmentally relevant hydrocarbon. Strikingly different results are obtained in the sulfite-dependent system. The epoxide-derived metabolites seen with the peroxyl radical systems are very minor products. Instead, two product peaks elute near the solvent fron on reverse-phase HPLC. These are apparently monohydroxy-CPP sulfonates. Such products may form either by the direct addition of the sulfite anion radical to the activated double bond of CPP or by peroxyl radical-dependent epoxidation of CPP followed by nucleophilic addition of sulfite. Precedent for both of these reactions has been reported with analogous benzo[a]pyrene derivatives. The occurrence of these radical-dependent transformations in intact mammalian systems has not been investigated, but the ability of all three model systems employed to convert CPP to potent bacterial mutagens implies that these pathways should be studied further. PMID- 2208597 TI - The 4S polycyclic aromatic hydrocarbon-binding protein: immunohistochemical localization in mice. AB - The 4S polycyclic aromatic hydrocarbon (PAH)-binding protein (PBP) is a cytoplasmic protein that binds PAHs with specificity and high affinity. We have used antisera for the PBP and unlabeled peroxidase anti-peroxidase immunohistochemistry to demonstrate its possible localization in cell types known to have xenobiotic metabolizing capabilities. Cellular sites of the PBP in liver, lung and kidney of C57BL/6 and DBA/2 mice were probed. The PBP was visualized in hepatocytes throughout the liver lobule and was not preferentially located in either centrilobular or periportal areas. However, cellular heterogeneity with respect to PBP content was clearly evident in the hepatocyte population. The positive reactivity correlated with substantial levels of benzo[a]pyrene (B[a]P) binding in liver cytosol. In the lung, the PBP was found in the bronchiolar epithelium and the alveolar septa, and was localized in ciliated and non-ciliated Clara and alveolar type II cells as well as in alveolar macrophages. In the kidney, the glomeruli and epithelia of proximal and distal convoluted tubules and collecting ducts were labeled. Staining for the PBP was greatest in the apical region of the pyramid and was localized in the epithelial lining of the collecting ducts. Relatively lower levels of the PBP were detected in the lung and kidney than in the liver. Staining was localized in the cytoplasmic compartment of cells in all tissues examined. Similar immunoreactivities were exhibited in the tissues of both C57BL/6 and DBA/2 mice. Treatment with beta naphthoflavone (beta NF) altered neither the intensity nor pattern of immunostaining. Furthermore, treatment with beta NF or isosafrole has no effect on the Kd and Bmax of B[a]P binding to liver cytosolic PBP. The results of our experiments demonstrate localization of the PBP to sites of active physiological response to PAH exposure. PMID- 2208598 TI - Mechanism of formation and 32P-postlabeling of DNA adducts derived from peroxidative activation of carcinogenic non-aminoazo dye 1-phenylazo-2 hydroxynaphthalene (Sudan I). AB - Horseradish peroxidase in the presence of hydrogen peroxide mediates the activation of carcinogenic 1-phenylazo-2-hydroxynaphthalene (Sudan I) to DNA bound products in vitro. The peroxidase activating system is greater than 10 times more effective with respect to DNA modification by Sudan I than the microsomal enzymes containing cytochrome P450. The DNA-binding reaction of the Sudan I metabolite(s) formed by the peroxidase system is dependent on Sudan I and H2O2 concentration and pH. Reactive intermediate(s) or product(s) of the Sudan I oxidation by peroxidase with a short half-life are responsible for the DNA modification. DNA modified by peroxidase-activated Sudan I becomes colored and has an absorption maximum at approximately 480 nm. The modification of DNA by Sudan I metabolites(s) formed by the peroxidase system is inhibited by some compounds of physiological importance (ascorbate, glutathione, Mg2+ ions) and by radical trapping agents (nitrosobenzene, methyl viologen). 32P-Postlabeling assay of the DNA modified by Sudan I activated by the peroxidase system indicates that the covalent DNA adduct formation is the principal type of the DNA modification. Four major and several minor adducts of deoxyribonucleotide 3',5'-bisphosphate from DNA with Sudan I metabolite(s) were detected by the classical Randerath 32P postlabelling assay as well as by the nuclease P1 version of the same method. PMID- 2208599 TI - Analysis of 1,3-butadiene and other selected gas-phase components in cigarette mainstream and sidestream smoke by gas chromatography-mass selective detection. AB - An analytical procedure was developed for the analysis of 1,3-butadiene, acrolein, isoprene, benzene and toluene in the gas phase of cigarette smoke and environmental tobacco smoke (ETS) utilizing cryogenic gas chromatography-mass selective detection (GC-MSD). The MSD was operated in the selective ion monitoring (SIM) mode. The compounds of interest eluted in less than 15 min. The gas phase of freshly generated mainstream smoke was introduced into the GC-MSD via a 10-port gas sampling valve on a puff-by-puff basis. This method minimizes the ageing of tobacco smoke. The levels of 1,3-butadiene in the mainstream smoke ranged from 16 to 75 micrograms/cigarette. The gas phase of sidestream smoke was trapped in methanol using three midget impingers at -78 degrees C. The amount of 1,3-butadiene in the sidestream smoke ranged from 205-361 micrograms/cigarette. The concentration of 1,3-butadiene in ETS in a smoke-filled bar amounted to 2.7 4.5 micrograms/m3. PMID- 2208600 TI - Sodium bisulfite induces morphological transformation of cultured Syrian hamster embryo cells but lacks the ability to induce detectable gene mutations, chromosome mutations or DNA damage. AB - The ability of sodium bisulfite to induce morphological transformation and mutagenesis of cultured Syrian hamster embryo cells was examined. Treatment of the cells at neutral pH for 15 min with 5-20 mM sodium bisulfite resulted in a dose-dependent increase in cell transformation but no induction of gene mutations measured at two genetic loci. Treatment of the cells for 24 h increased the level of transformation, but also failed to induce chromosome aberrations, aneuploidy or DNA strand breaks in the cells. The only positive response for a DNA alteration was an increase in sister chromatid exchanges, but this effect was observed only with the longer exposures and not with the 15 min exposure, which also transformed the cells. Possible mechanisms for bisulfite-induced cell transformation are discussed. PMID- 2208601 TI - Is 8-hydroxydeoxyguanosine a mediator of carcinogenesis by a choline-devoid diet in the rat liver? AB - The mechanism(s) by which a diet devoid of choline (CD) induces hepatocellular carcinomas in rats remains unknown. Although animals fed this diet develop nuclear lipid peroxidation, suggesting oxidative DNA damage, there is no direct evidence that this occurs. In this study, 8-hydroxydeoxyguanosine (8-OHdG), a DNA adduct generated by reactive oxygen species, was analyzed in the liver of rats fed a CD diet and in controls receiving a choline-sufficient (CS) diet. After partial hepatectomy, the animals were injected with diethylnitrosamine (DEN, 50 mg/kg body wt) or with saline and fed a CD or CS diet for 24 weeks. While liver DNA from rats injected either with DEN or saline and fed a CS diet did not show detectable amounts of the nucleotide, those who were fed DEN/CD and saline/CD demonstrated similar, easily measurable levels of 8-OHdG. These results indicate that there is a positive association between the continuous administration of a CD diet and the production of 8-OHdG in liver DNA, and support the idea that oxidative DNA damage is involved in carcinogenesis by a CD diet. PMID- 2208602 TI - Marked nitrosation by stimulation with lipopolysaccharide in ascorbic acid deficient rats. AB - Marked formation of N-nitrosothioproline (N-nitrosothiazolidine-4-carboxylic acid) by stimulation with Escherichia coli lipopolysaccharide (LPS) was demonstrated in ascorbic acid-deficient mutant rats (osteogenic disorder syndrome rats; ODS rats) unable to synthesize ascorbic acid. The amounts of urinary nitrate and N-nitrosothioproline excretion after thioproline administration was measured in ODS rats with and without ascorbic acid supplement before and after the injection of LPS. LPS caused marked increase of urinary nitrate excretion in both groups. Urinary N-nitrosothioproline excretion increased 6-fold after LPS injection in ODS rats not supplied with ascorbic acid, but supplement with ascorbic acid markedly decreased the excretion of N-nitrosothioproline. PMID- 2208603 TI - Para-methoxyphenol strongly stimulates cell proliferation in the rat forestomach but is not a promoter of rat forestomach carcinogenesis. AB - The modifying effects of para-methoxyphenol (PMP) second stage treatment on N methyl-N'-nitro-N-nitrosoguanidine (MNNG)-initiated rat forestomach carcinogenesis were investigated. Groups of 15 6 week old male F344 rats were given a single intragastric administration of 150 mg/kg body wt MNNG and starting 1 week later were administered powdered diet containing 2.0, 1.0, 0.5, 0.25 or 0% PMP until they were killed at week 52. PMP caused epithelial damage and hyperplasia in a dose-dependent manner in the forestomach epithelium, but nevertheless was not associated with any increase in the incidence of either papillomas or squamous cell carcinomas. The results thus clearly indicated that stimulation of cell proliferation does not necessarily correlate with promotion in the second stage of two-stage forestomach carcinogenesis. PMID- 2208604 TI - Liposome-encapsulated hemoglobin: an oxygen-carrying fluid. AB - From the original concept of encapsulating hemoglobin in an inert shell, LEH has evolved into a fluid proven to carry oxygen, capable of surviving for reasonable periods in the circulation, and amenable to large-scale production. The formula for the outer shell evolved from synthetic, nonlipid materials, to egg-lecithin based lipid mixtures, to distearoyl-phosphatidylcholine-based blends. The fabrication technology started with the production of milliliter quantities and methods detrimental to the hemoglobin and developed into high-pressure extrusion systems producing multi-liter quantities without damaging the hemoglobin. The development of methods for analysis and quality control of LEH has been difficult: even techniques for measuring basic characteristics of size and methemoglobin are still being standardized. In vivo studies have established that LEH has a circulation half-life of 16-20 hr and can carry oxygen sufficient to sustain life, but safety has yet to be proven. In each of the general areas mentioned above, there are opportunities for further improvement and characterization. The source of the hemoglobin and the coencapsulation of hemoglobin modifiers needs to be reassessed now that human hemoglobin has been cloned and functional hemoglobin can be produced by using fermentation techniques. The development of routine methods for quality control and assurance must accompany the production of large quantities of LEH for preclinical studies. Whether or not the LEH can and should be manufactured as a lyophilized product must be assessed. Animal studies must done to prove safety as well as efficacy in a variety of clinical models, including hemorrhagic and septic shock as well as various levels of isovolemic exchange. One approach toward the improvement of the LEH is to alter the liposome surface to increase its biocompatibility. The evolution of biocompatible liposome surfaces has included carbohydrate moieties, as carbohydrates are expressed on the majority of biological membrane surfaces including the red cell. It has been demonstrated that inclusion of carbohydrate components such as gangliosides into the liposomal bilayer results in increased circulation times. As a result, these ganglioside-containing liposomes may exhibit a reduced impact on the RES system. Goins et al. have examined methods of introducing the ganglioside GM1 into LEH preparations. The long-term preservation of LEH is essential for its use by paramedics both in civilian and military trauma settings.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2208606 TI - Calcium-free reperfusion prevents mitochondrial calcium accumulation but exacerbates injury. AB - Excessive accumulation of intracellular calcium has been proposed as a mediator of cell injury during ischemia and reperfusion. To test whether restriction of extracellular calcium might ameliorate hepatic injury following hypothermic ischemic preservation, isolated perfused rat livers were reperfused with a medium with normal extracellular calcium (mM-Ca) or no added calcium (microM-Ca) following 26 hr preservation at 4 degrees C. During reperfusion mitochondria from mM-Ca livers accumulated calcium and respiratory activity declined. Although mitochondrial calcium accumulation was prevented by microM-Ca reperfusion, damage to respiratory activity was exacerbated. Edema formation and loss of gluconeogenesis were similarly exacerbated in microM-Ca. This accelerated damage was not reversed by subsequent restoration of calcium. These results demonstrate that rather than ameliorating cell injury, calcium deprivation during reperfusion exacerbates damage to mitochondrial and cellular functions. Thus, cellular or mitochondrial calcium accumulation does not appear to be a sine qua non for hepatocyte injury during reperfusion following hypothermic ischemia. PMID- 2208605 TI - Oxygen-derived free radicals induced cellular injury in superior mesenteric artery occlusion shock: protective effect of superoxide dismutase. AB - This study was designed to investigate the beneficial effect of administration of exogenous superoxide dismutase (SOD) on the inhibition of lipid peroxidation and cellular protection during superior mesenteric artery occlusion shock in rats. Wistar rats were anesthetized with sodium pentobarbital (30 mg/kg body weight), and the superior mesenteric artery occlusion shock model was induced by clamping the superior mesenteric artery for a 60-min period and then releasing the arterial clamp. The following parameters were determined: 1) average arterial blood pressure; 2) survival rate and mean survival time (MST); 3) activities of plasma lysosomal enzymes beta-glucuronidase (beta-G) and acid phosphatase (ACP); and 4) the contents of malondialdehyde (MDA) in visceral tissues. The SOD group received 15,000 U/kg body weight SOD intra-arterially 15 min before release of the clamp. The saline group received intra-arterially a corresponding volume of saline given to the SOD group. The superior mesenteric artery of rats in the control group was not clamped. In the saline group, the contents of MDA presented significant increases (P less than 0.05) in bowel and heart tissues at 1 hr after release of the clamp and showed more significant increases (P less than 0.01 0.05) in bowel, heart, liver, and lung tissues at 2 hr after release of the clamp, when compared with control values. However, the contents of MDA in bowel and heart tissues in the SOD group showed significant decreases (P less than 0.05) compared with values in the saline group and had insignificant changes (P greater than 0.05) compared with control values at 1 hr after release of the clamp. The contents of MDA in bowel, heart, and lung tissues in the SOD group were still lower than those in the saline group (P less than 0.05) at 2 hr after release of the clamp, although they were higher than those in the control group (P less than 0.05). The activities of plasma lysosomal enzymes in the SOD group were much lower than those in the saline group at 1 and 2 hr after release of the clamp. The mean survival time of shocked animals was prolonged when treated with SOD. These results suggested that administration of exogenous SOD may protect cells against lipid peroxidation injury mediated by oxygen-derived free radicals, depress the release of lysosomal enzymes, and prolong the mean survival time of shocked animals. PMID- 2208607 TI - The vascular response to adrenergic stimulation in pithed rats following endotoxin. AB - In vivo and in vitro studies have shown that the vascular response to catecholamine is attenuated during endotoxemia. The mechanism of such attenuation is complex and might involve high catecholamine-induced desensitization of adrenoceptors. The purpose of this study was to assess the vascular response to adrenergic stimulation after endotoxin (ETX) administration in pithed rats. In pithed rats, sympathetic outflow is controlled by stimulation, ETX does not elevate norepinephrine (NE), and there are no compensatory reflexes. Rats were pithed, curarized, and adrenal-demedullated. Preganglionic thoracolumbar nerves were stimulated (3 Hz, 10 V, 0.5 msec) for 1 hr after pithing, at which time the first set of frequency and NE-dose responses were assessed by measuring the peak increase in diastolic blood pressure. Intravenous ETX (1.5 mg/kg or 0.5 mg/kg) or saline was administered immediately after these measurements. A sham group was designed to mimic the falling blood pressure pattern seen in the endotoxin group during 1 hr after ETX was given by gradually decreasing the stimulation frequency. The second set of frequency and NE-dose responses were evaluated 1 hr after ETX, saline, or sham treatment. Plasma NE and epinephrine (EPI) were determined before and 1 hr after ETX (1.5 mg/kg) or saline injection. The results showed that blood pressure response to adrenergic stimulation was markedly attenuated in pithed rats following both high and low doses of ETX compared with the saline and sham groups. Plasma NE was not elevated by ETX insult in pithed rats. We propose that mechanisms other than high-catecholamine-induced adrenergic desensitization or hypotension account for the attenuated adrenergic responsiveness of the vasculature following ETX. PMID- 2208608 TI - Effects of endothelin on the lethality induced by platelet-activating factor or endotoxin in the mouse. AB - Platelet-activating factor (PAF) is a mediator that decreases cardiac output and total peripheral resistances leading to profound hypotension. It seems to be involved in shock states and in the deleterious effects of endotoxin. As the natural peptide endothelin (ET) shows potent vasoconstrictor properties, we evaluate its activity towards PAF and endotoxin-induced lethality in mice. ET, at doses which per se did not exert any effects on mice vitality, produced a dose dependent decrease in the PAF-induced lethality with a total protection at 5 micrograms/kg. But conversely to these results, ET potentiated the mortality induced by endotoxin. These results suggest that ET or endothelin analogs could be worthy for therapeutic use in some types of shock, at least when endotoxin is not involved. Complementary studies are necessary to strengthen these preliminary results. PMID- 2208609 TI - Blood flow in microvascular networks. Experiments and simulation. AB - A theoretical model has been developed to simulate blood flow through large microcirculatory networks. The model takes into account the dependence of apparent viscosity of blood on vessel diameter and hematocrit (the Fahraeus Lindqvist effect), the reduction of intravascular hematocrit relative to the inflow hematocrit of a vessel (the Fahraeus effect), and the disproportionate distribution of red blood cells and plasma at arteriolar bifurcations (phase separation). The model was used to simulate flow in three microvascular networks in the rat mesentery with 436,583, and 913 vessel segments, respectively, using experimental data (length, diameter, and topological organization) obtained from the same networks. Measurements of hematocrit and flow direction in all vessel segments of these networks tested the validity of model results. These tests demonstrate that the prediction of parameters for individual vessel segments in large networks exhibits a high degree of uncertainty; for example, the squared coefficient of correlation between predicted and measured hematocrit of single vessel segments ranges only between 0.15 and 0.33. In contrast, the simulation of integrated characteristics of the network hemodynamics, such as the mean segment hematocrit or the distribution of blood flow velocities, is very precise. In addition, the following conclusions were derived from the comparison of predicted and measured values: 1) The low capillary hematocrits found in mesenteric microcirculatory networks as well as their heterogeneity can be explained on the basis of the Fahraeus effect and phase-separation phenomena. 2) The apparent viscosity of blood in vessels of the investigated tissue with diameters less than 15 microns is substantially higher than expected compared with measurements in glass tubes with the same diameter. PMID- 2208610 TI - Effects of the spatial dispersion of acetylcholine release on the chronotropic responses to vagal stimulation in dogs. AB - We determined the effects of changing the spatial dispersion of acetylcholine release on the phase-dependent chronotropic responses to vagal stimulation in anesthetized dogs. We stimulated the vagus nerves with one brief burst of electrical pulses each cardiac cycle, and we changed the timing of the stimulus by a small, constant amount each cardiac cycle to scan the entire cycle. To vary the heterogeneity of acetylcholine release, we changed the voltage of the stimulus pulses over a range of submaximal values. To achieve the maximum homogeneity of acetylcholine release, we used supramaximal voltages, and we varied the level of acetylcholine release from each excited fiber by changing the number of pulses per burst. We used the average cardiac cycle length of the phase response curve to assess the overall vagal effect, independent of its timing within the cardiac cycle. We found that the amplitude of the phase-response curve varied directly and the minimum-to-maximum phase difference varied inversely with the overall efficacy of vagal activity. However, for any given alteration in the overall efficacy, the specific changes in the characteristics of the phase response curve did not depend on whether the alteration was achieved by varying the number of pulses per burst or by varying the stimulus voltage. Therefore, we conclude that although the cardiac chronotropic response is very sensitive to changes in the timing of vagal stimulation, it is not influenced appreciably by the spatial dispersion of acetylcholine release from the vagal nerve endings over a wide range of stimulation strengths. PMID- 2208611 TI - Is fibrillation chaos? AB - Ventricular fibrillation is examined to determine whether it is an instance of deterministic chaos. Surface ECGs from dogs in fibrillation were used to generate a state space representation of fibrillation. Our analysis failed to identify a low-dimensional attractor that could be associated with fibrillation. The results suggest that fibrillation is similar to a nonchaotic random signal. We note, however, that such random-looking but nonchaotic behavior can also be generated by a nonlinear deterministic system. PMID- 2208612 TI - Heat released during relaxation equals force-length area in isometric contractions of rabbit papillary muscle. AB - It has been claimed that the mechanical performance and the related energy turnover of the left ventricle can be reliably predicted on the basis of its time varying elastance behavior. In its most elementary form, this behavior can be mathematically described by E(t) = P(t)/[V(t)-Vd], where E is ventricular elastance, t is time, P is ventricular pressure, V is ventricular volume, and Vd is the intercept of the end-systolic pressure-volume line on the volume axis. To find out how this behavior of the ventricle as a whole is related to the properties of the myocardium, we tested the energetic prediction for the ventricle that the pressure-volume area of an isovolumic contraction equals the energy released in relaxation in experiments on isolated rabbit papillary muscle at 20 degrees C. To that end, the energy (joules) contained by the force-length area of the muscles, contracting isometrically, was compared with the heat (joules) liberated in relaxation as measured with thermopiles. Mechanical performance of the muscles was varied by altering initial muscle length and external calcium. The slope of the resulting relation between force-length area and heat liberated in relaxation (n = 26) was not significantly different from unity. Thus, the energetic prediction of the time-varying elastance model developed for the whole left ventricle was confirmed by experiments on rabbit papillary muscle at 20 degrees C. PMID- 2208613 TI - In vivo measurement of myocardial protein turnover using an indicator dilution technique. AB - We applied a nondestructive tracer technique, previously developed for measuring skeletal muscle protein turnover, to the measurement of myocardial protein turnover in vivo. During a continuous infusion of L-[ring-2,6-3H]phenylalanine to anesthetized, overnight-fasted dogs, we measured the uptake of radiolabeled phenylalanine from plasma and the release of unlabeled phenylalanine from myocardial proteolysis using arterial and coronary sinus catheterization and analytic methods previously applied to skeletal muscle. Using these measurements, together with a model of myocardial protein synthesis that assumes rapid equilibration of tracer specific activity between myocardial phenylalanyl-tRNA and circulating phenylalanine, we estimated the rates of heart protein synthesis and degradation. The rate of heart protein synthesis was also estimated directly from the incorporation of labeled phenylalanine into tissue protein. The use of [3H]phenylalanine was compared with L-[1-14C]leucine in the measurement of heart protein turnover in dogs given simultaneous infusion of both tracers. Leucine uptake and release by the myocardium exceeded that of phenylalanine by 3.1 +/- 0.4- and 1.7 +/- 0.3-fold, respectively, consistent with leucine's 2.4-fold greater abundance in heart protein and its metabolism via other pathways. Phenylalanine is the preferred tracer for use with this method because of its limited metabolic fate in muscle. One theoretical limitation to the method, slow equilibration of circulating labeled phenylalanine with myocardial phenylalanyl tRNA, was resolved by comparison of these specific activities after a 30-minute infusion of labeled phenylalanine in the rat. A second, empirical limitation involves precision in the measurement of the small decrements in phenylalanine specific activity that occur with each pass of blood through the coronary circulation. This was addressed by improving the precision of both the measurements of phenylalanine concentration and phenylalanine specific activity using high-performance liquid chromatography. We conclude that the in vivo measurement of phenylalanine tracer exchange across the myocardium permits the nondestructive estimation of heart protein turnover in the intact animal. PMID- 2208614 TI - Sarcolemma, sarcoplasmic reticulum, and sarcomeres as limiting factors in force production in rat heart. AB - Inotropic interventions were compared with respect to their maximum effect on force of contraction in rat myocardium to identify limiting steps in calcium handling. Peak force, sarcomere length, and action potentials were measured in thin ventricular trabeculae. Relevant control conditions were stimulation frequency, 0.2 Hz; [Ca2+]o, 1 mM; [K+]o, 5 mM; [Na+]o, 150 mM. The inotropic interventions and results were as follows. 1) The interventions of high [Ca2+]o, low [Na+]o, high [K+]o, addition of tetraethylammonium chloride, or postextrasystolic potentiation resulted in approximately the same (within 5%) maximum force (Fmax). Above the respective optimum doses, force declined and aftercontractions were often observed. Combinations of the different interventions never enhanced force to above Fmax. This suggests that Fmax is determined by a maximum level of Ca2+ in the sarcoplasmic reticulum, above which spontaneous release occurs. 2) Sr2+ (10 mM) caused an increase of force to 1.3 X Fmax and lengthening of contraction and action potentials. The force-sarcomere length relation was, then, similar to that in skinned fibers at maximum activation. Hence, 1.3 X Fmax reflects saturation of the sarcomeres. We postulate that a large influx of Sr2+ during the long action potential can circumvent the reticulum and activate the sarcomeres directly. When the reticulum was blocked with ryanodine, maximum force of tetanic contractions was about 1.1 X Fmax. This result supports the above conclusions. 3) Isoproterenol increased force to a maximum that was 20% below Fmax and shortened the contraction. This may be due to a decreased sensitivity of the sarcomeres to Ca2+ or to stimulation of the Ca2+ pump in the reticulum, that is, an increasing fraction of the released Ca2+ is sequestered before it can activate the sarcomeres. Thus, three factors that limit force production were identified, depending on the inotropic stimulus. PMID- 2208615 TI - Effects of coronary venous pressure on left ventricular diastolic distensibility. AB - Coronary arterial pressure and flow are known to influence left ventricular (LV) diastolic distensibility, but the influence of coronary venous pressure is unknown. To test the hypothesis that increased coronary venous pressure leads to an increase in LV wall volume and a decrease in LV diastolic distensibility, we studied excised, blood-perfused LV isovolumic dog hearts without the pericardium. In protocol I (n = 8), to raise coronary venous pressure the pressure of right atrium (RA) and right ventricle (RV) was increased by the height of a blood reservoir connected with a cannula that opened in both the RA and RV. In protocol II (n = 7), to isolate the effect of RV enlargement on LV diastolic distensibility (direct ventricular interaction), an isovolumic RV balloon was used with coronary venous pressure held constant at 0 mm Hg. Changes in LV diastolic distensibility were assessed by shifts of the LV end-diastolic pressure volume relation. Changes in LV wall volume were detected by subepicardial segment length at end-diastole. The mean pressures of RA and RV (protocol I) and RV balloon only (protocol II) were increased from 0 to 15 and 30 mm Hg over a range of LV volume. In protocol I, when RA.RV pressure was increased from 0 to 30 mm Hg at three levels of LV volume (22 +/- 2, 31 +/- 3, and 40 +/- 3 ml), LV end diastolic pressures increased significantly from 5.2 +/- 0.3 to 11.2 +/- 1.5, from 10.4 +/- 0.3 to 18.2 +/- 1.2, and from 20.2 +/- 1.0 to 28.8 +/- 1.2 mm Hg, respectively. In protocol II, when RV balloon pressure was increased from 0 to 30 mm Hg at the three LV volumes (21 +/- 3, 31 +/- 3, and 41 +/- 4 ml), LV end diastolic pressures showed smaller increases from 5.2 +/- 0.2 to 6.6 +/- 0.2, from 9.8 +/- 0.3 to 11.6 +/- 0.6, and from 19.0 +/- 0.5 to 21.4 +/- 0.8 mm Hg, respectively. In both protocols, the LV end-diastolic pressure-volume relation shifted upward in a nearly parallel fashion, but the shift was much greater in protocol I than in protocol II. Despite constant LV volume, an increase in LV wall dimension in protocol I was significant and much greater than that in protocol II. From these results, we conclude that increased coronary venous pressure decreases LV diastolic distensibility with increasing LV wall volume, and this mechanism appears to act independently of diastolic ventricular interaction caused by RV enlargement. PMID- 2208616 TI - Cloning and characterization of a vertebrate cellular myosin regulatory light chain complementary DNA. AB - We have isolated two series of complementary DNAs (cDNAs) from a chicken gizzard cDNA library encoding two isoforms of phosphorylatable myosin regulatory light chain (RLC). One of the cDNAs encodes a previously isolated smooth muscle myosin RLC (also referred to as LC20-A); the other encodes a protein that shares 92% homology with the LC20-A isoform. The phosphorylatable threonine and serine residues at positions 18 and 19 of the two myosin RLC sequences are conserved. The two cDNAs are 81% homologous at the nucleotide level over the coding region; the 5' and 3' untranslated regions are divergent. Most of the DNA nonhomology in the coding region does not affect the protein sequence, indicating strong evolutionary conservation pressure to maintain the myosin RLC structure. Northern blot analysis using 3' untranslated region probes reveals restrictive tissue specific expression of one myosin RLC isoform (LC20-A) in smooth muscle tissue and not in other tissues examined. In contrast, the novel myosin RLC isoform messenger RNA (mRNA) is uniformly expressed in all smooth and nonmuscle tissues examined and is designated as cellular myosin RLC for this reason. Our results indicate that cellular and smooth muscle myosin RLC isoforms are distinct and are encoded by separate genes. This report describes the cloning of a novel vertebrate cellular myosin RLC mRNA that differs from previously characterized smooth muscle RLC isoform mRNAs in both primary sequence and expression pattern. PMID- 2208617 TI - Synergistic inhibition of platelet aggregation by fibrinogen-related peptides. AB - We have evaluated the ability of the fibrinogen-related peptides Gly-Arg-Gly-Asp Ser (GRGDS), Gly-Gln-Gln-His-His-Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val (gamma chain peptide), and Gly-Pro-Arg-Pro (GPRP) to inhibit platelet aggregation in platelet-rich plasma individually and in combination. When used alone, GRGDS totally inhibited ADP-induced aggregation of human platelets in platelet-rich plasma; however, the maximum inhibitory effect of the other peptides was less than 80%. The concentrations necessary to inhibit platelet aggregation in plasma by 50% were 100 mumols/l and 1 and 3.2 mmol/l for GRGDS, gamma-chain peptide, and GPRP, respectively. When evaluating the effect of peptide mixtures, we discovered that the combination GPRP + GRGDS worked together synergistically (p less than 0.001, analysis by surface response methodology), whereas GPRP + gamma-chain peptide did not. For example, our analysis indicated that a mixture of 50 mumols/l GRGDS plus 180 mumols/l GPRP would produce 50% inhibition of platelet aggregation. This is an effect twofold greater than that produced by 50 mumols/l GRGDS alone, and one that would require an 18-fold greater concentration of GPRP if used alone. These data indicate that the combination GPRP + GRGDS inhibited platelet aggregation in plasma in a synergistic fashion and suggest the potential value of their combined use in antithrombotic therapy. PMID- 2208618 TI - Species-dependent effects of adenosine on heart rate and atrioventricular nodal conduction. Mechanism and physiological implications. AB - This study 1) compares the negative chronotropic and dromotropic actions of adenosine in guinea pig, rat, and rabbit hearts; 2) investigates the mechanism(s) for the different responses; and 3) determines the physiological implications. Isolated perfused hearts were instrumented for measurement of atrial rate and atrioventricular (AV) nodal conduction time. Differences in metabolism of adenosine were determined in the absence and presence of dipyridamole (nucleoside uptake blocker) and erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA, adenosine deaminase inhibitor). Dipyridamole plus EHNA decreased adenosine's EC50 for the negative dromotropic effect by 14-fold in guinea pig heart and 1.6-fold in rat heart. This is consistent with the greater number of [3H]nitrobenzylthioinosine binding sites measured in membranes from guinea pig (1,231 +/- 68 fmol/mg protein) compared with rat (302 +/- 31 fmol/mg protein) and rabbit (260 +/- 28 fmol/mg protein) atria. The potency of adenosine to slow atrial rate and prolong AV nodal conduction time was greater in guinea pig than in rat or rabbit hearts. This rank order of potency correlated well with the number of binding sites for the specific adenosine receptor radioligand 125I-aminobenzyladenosine in guinea pig (102 +/- 13 fmol/mg protein), rat (11 +/- 0.5 fmol/mg protein), and rabbit (8 +/- 1 fmol/mg protein) atrial membranes. Hypoxia increased the rate of adenosine release by severalfold and caused slowing of heart rate and AV block. In spontaneously beating hearts, the main effect of hypoxia was a slowing of ventricular rate, which in the guinea pig heart was due to AV block and in the rat heart to atrial slowing. In atrial paced hearts, hypoxia caused a marked prolongation of AV nodal conduction time in guinea pig (39 +/- 4 msec) and rabbit (29 +/- 5 msec) hearts, but only small effect in rat hearts (10 +/- 2 msec). The differences in response to hypoxia could be accounted for by the species dependent differences in the 1) amount of adenosine released and metabolized, 2) sensitivity of the hearts to adenosine, and 3) dependency of AV nodal conduction on atrial rate. The findings indicate that the results from physiological or pharmacological studies on adenosine in one species may not be applicable to others, and the ultimate effect of adenosine and hypoxia is to slow ventricular rate. PMID- 2208619 TI - [Clinical observations on the treatment of hookworm, Ascaris and Trichuris infection with oxibendazole]. AB - 340 cases of hookworm infection, 196 cases of ascariasis and 178 cases of trichuriasis were treated with an anthelmintic, oxibendazole, 15mg/kg.d x 3d; 102, 70 and 66 cases of respective infections were treated with pyrantel 10mg/kg.d x 3d and 108, 74 and 63 cases took placebo for comparison and as control under double-blind observations. Re-examinations of the stool were performed after the treatment. Among the cases treated with oxibendazole, the egg negative conversion rates of hookworm, Ascaris and Trichuris were 70.3-80.6%, 92.5-97.8 and 67.0-71.0% respectively. The egg reduction rates of hookworm were 98.1-98.6%. The larval negative conversion rates of Ancylostoma duodenale and Necator americanus were 77.7 and 83.2% respectively. Among the cases treated with pyrantel, the egg negative conversion rates of the three above mentioned parasites were 73.5, 90.0 and 28.8% respectively. The egg reduction rate of hookworm was 98.8%. Among the cases treated with placebo, the egg negative conversion rates of the three above mentioned parasites were 6.5, 29.7 and 7.9%. No marked adverse reactions were observed by clinical and laboratory examinations. PMID- 2208621 TI - [Ultrastructure of metacercarial membrane and immunohistochemical localization of metacercarial membrane reaction of Paragonimus westermani]. AB - The ultrastructure of the tegument of the early excysted P. westermani metacercariae was observed with transmission electron microscope. The tegument was fine and dense in texture, containing a lot of disk-like bodies and a few mitochondria. The outer-plasma membrane was clear and intact. After the metacercariae were incubated in rabbit anti-serum for 3 hours, metacercarial membrane reaction (MMR) appeared closely to the outer plasma membrane and the tegument was damaged. Indirect peroxidase-labelled immunohistochemical technique was used to identify the location of the MMR at ultrastructural level. The result showed that the antibody-antigen complex was localized on the tegumental surface of the worm. The data constituted the evidence that the MMR resulted from the antibody-antigen reaction and the tegumental surface was the reaction site for the MMR. PMID- 2208620 TI - [Observation on the infectivity of Leishmania donovani from different areas to Phlebotomus alexandri from Xinjiang]. AB - Hamsters or cotton rats were infected with 3 stocks of L. donovani, one of which had been isolated from an infected Ph. major wui in Xinjiang desert area and 2 from kala azar patients in a mountain area of Gansu and in a plain area of Henan respectively. The purpose of the study was to compare the infectivity of the parasites from different geographic areas through artificial infection of Ph. alexandri. Sandflies were dissected in 4, 6, 8 and 10 days after feeding on the infected animals to observe the growth and development of promastigotes of different isolates in their alimentary tracts. Evaluation was made on 3 aspects, i.e. infection rates, infectiosity and migration of promastigotes in sandflies. It was demonstrated that Xinjian isolate of L. donovani appeared to be particularly adapted to Ph. alexandri followed by Gansu isolate, the Henan isolate did not show good adaptation to this sandfly, because the number of promastigotes declined and the infection rate dropped after the digestion of the blood meal in the stomach of the sandflies. It seems that the phenomenon was related to the biological characteristics of L. donovani isolates. These results coincided with those of McAb dot ELISA (Qu,1987) and K-DNA dot hybridization (Lu & Hu 1988) for identification of L. donovani from different areas in China, and were also in parallel to the diverse epidemiological characteristics of different kala azar endemic areas (Guan, 1976). It is reasonable to infer that there may exist different geographical strains of L. donovani in China. PMID- 2208622 TI - [Preliminary studies on transaminase of Oncomelania snail]. AB - By paper chromatography, the tissue homogenate of Oncomelania snails was shown to form glutamic acid at the expense of alpha-ketoglutarate plus aspartic acid, alanine or arginine respectively. The existence of alanine-glutamate, aspartate glutamate and arginine-glutamate transaminase in Oncomelania snail was demonstrated. By using colorimetric method, the activity of aspartate-glutamate transaminase (GOT) and alanine-glutamate transaminase (GPT) of Oncomelania snail was 1.64 +/- 0.01 and 0.99 +/- 0.01 mumol/h.mg protein respectively. GOT and GPT were not inhibited by 2 ppm bromoacetamide, but the activity of GPT was suppressed (40%) by 2 ppm nicotinanilide. A combination of 0.5 ppm bromoacetamide and 0.5 ppm nicotinanilide had no synergitic molluscicidal effect. PMID- 2208623 TI - [Soluble protein and esterase isozyme analysis of adult female Anopheles stephensi after Plasmodium yoelii yoelii-infected blood meal]. AB - In this paper, the system of Anopheles stephensi and Plasmodium yoelii yoelii was used as animal model. The soluble protein and esterase isozymes of adult female mosquitoes at various times after taking noninfected and plasmodia-infected blood meal were investigated. The result shows that the amount of soluble protein in plasmodia-infected mosquitoes was lower than that in noninfected ones (P less than 0.01); the activity and electrophoretic patterns of EST in infected mosquitoes being also different from those of the noninfected ones. PMID- 2208624 TI - [Observation on polytene chromosomes of the ovarian nurse cell of Anopheles minimus from Guangxi]. AB - The ovarian nurse cell's polytene chromosomes of An. minimus exist as 5 arms, the telocentric X chromosome, the submetacentric chromosome 2 and the metacentric chromosome 3. The X chromosome is easily recognized by its length and shuttle shaped zone 6. The most important characteristics is that each autosome arm has one to three big puffs. Among the 46 zones, 7A, B and 19C in 2R which is the longest arm in the complement, 28A and 20A, B in 2L, 30A, B and 37D in 3R and 46D and 38A, B in 3L are considered as characteristic zones. It is proposed that this map might be considered as the "standard" map of the ovarian nurse cell's polytene chromosomes for An. minimus from Guangxi. PMID- 2208625 TI - [In vitro cultivation and scanning electron microscopic observation of Plasmodium berghei]. AB - To compare the effects of sera on the growth of Plasmodium berghei, the erythrocytic stages were cultured with rat serum, human umbilical cord serum, human B-type serum, rabbit serum, calf serum and calf serum with hypoxanthine respectively. The topography of the erythrocyte and parasite cultured with calf serum were observed before and 12, 20 and 28 hours after cultivation. All of the sera used did not effectively improve the long-term culture of P. berghei, regardless of some differences in short-term cultures. Under SEM, erythrocytes agglutinated with each other and the surface adhesive materials on the erythrocytes and parasites agglomerated gradually with the cultivation time. The results suggested that the surface adhesive materials were correlated with the destruction of erythrocytes, malnutrition of the parasites and blockade of merozoite reinvasion. PMID- 2208626 TI - [Studies on the karyotypes of Fasciola spp]. AB - The karyotypes of diploid and triploid forms of the common liver fluke were analysed by air-drying method. The chromosome number of diploid form was 2n = 20, n = 10, and the karyotype consists of the chromosomes with 2M, 4Sm, 3St, 1T. There were a number of similarities between the karyotypes of diploid form and triploid form except that the chromosome number of the triploid was 3n = 30 and n = 10. Judging from the shape of adult worms and their life cycle, the worm of the diploid form is similar to F. gigantica while the worm of the triploid form is similar to F. hepatica. In several specimens of the triploid worms there were some cells having 20 chromosomes that were composed of 10 monovalent chromosomes and 10 divalent chromosomes. This kind of cell, in a group of 8 cells, was primary spermatocyte. According to the measurement, these chromosomes could be classified into 10 pairs and each pair was made up by one monovalent chromosome and one divalent chromosome. The karyotype of these chromosomes was similar to that of the triploid form. It is a rare phenomenon that one set of monovalent chromosomes and one set of divalent chromosomes co-exist during the same metaphase. PMID- 2208627 TI - [Detection of serum antibodies in jirds against antigens of Brugia malayi]. AB - The indirect fluorescent antibody test (IFA) using the infective larva (L3), adult worm (A) and microfilaria (Mf) antigens was applied to detect anti-filarial antibodies in jirds (Meriones unguiculatus) infected with Brugia malayi. The antibodies against L3 appeared within 3 weeks after infection, followed by A and Mf. The serum antibody levels in the jirds with positive infection were compared with those in the jirds with negative infection. Before appearance of microfilaria, there was insignificant difference between these two groups. However, significant difference was observed after the appearance of microfilaria. The method of sonicating L3 and Mf fragment antigens used in this study is simple, and its results are easy to observe. PMID- 2208628 TI - [Detection of serum immunoglobulins in pulmonary acariasis patients]. AB - The IgG, IgA, IgM levels in sera of 51 patients suffered from pulmonary ascariasis and the serum IgE level in 16 of them were determined using single immunodiffusion technique or biotin-avidin enzyme immunosorbent assay (ABC ELISA). The results showed that the IgM level of the patients was approaching to that of the normals while IgG (169.77 +/- 46.91 U/ml), IgA (308.39 +/- 91.83 U/ml) and IgE (458.90 +/- 273.64 U/ml) levels of the patients increased significantly. This suggests that some components of mites may have stimulated the humoral immunoreactions of the host. PMID- 2208629 TI - [Epidemiological characteristics and control of filariasis in Hunan Province]. AB - Of 98 counties or cities in Hunan Province, 55 were endemic areas of filariasis. The average microfilaria rate was 5.64% (180,046/3,194,102), and the incidence of advanced filariasis, including elephantiasis and hydrocele was 3.29%. The number of filariasis patients in the whole province was estimated to be 1.63 million, comprising 1.25 million of microfilaremia cases, Culex fatigans and Anopheles hyrcanus sinensis were the major vectors of bancroftian and malayan filariasis respectively in the province. Control strategies concentrated on the elimination of infection source were implemented on the basis of extensive investigations, and the ensuing examination and treatment of filariasis cases in pilot areas prior to the implementation of province-wide filariasis control. Repeated blood examinations and medications for 3-4 times were carried out in hypo-endemic areas of malayan filariasis, whereas mass treatment with hetrazan-medicated salt containing 0.2% to 0.5% DEC was carried out in meso- and hyper-endemic areas of bancroftian filariasis as well as those situated in remote mountainous regions for six months. Subsequent evaluation and clearance checking showed that microfilaria rate of the whole province has already dropped to less than 1%. That filariasis was basically eliminated in Hunan was recognized by the Evaluation Mission Group sent by the Ministry of Public Health in 1986. PMID- 2208630 TI - [Preliminary study on the surface antigen gene of Plasmodium malariae]. AB - The genomic Hind III lambda gt1149 library from Plasmodium malariae was screened with two types of oligonucleotides, both of which were from the P190 gene of P. falciparum. One, MAD20 type, was made from spanning nucleotides 4488-4562 in the P190 gene of MAD20 strain and another, K1 type, was made from spanning nucleotides 3652-3692 in the P190 of K1 strain. Both were end-labelled with 32P ATP as probes before hybridization. Two clones were selected. One clone, designated lambda MSA-1, was specifically recognized by the MAD20 type oligo probe; the other, designated lambda MSA-2, by the K1 type oligo probe. lambda MSA 1 and lambda MSA-2 inserts were obtained by Hind III digestion of the two clone phage DNA. The analysis of the two inserts showed that the size of lambda MSA-1 is 5.5 kb whilst that of lambda MSA-2 is 3.5kb. The MSA-1 and MSA-2 inserts recloned into PUC8 were digested with the restriction enzymes Bg1 II, EcoR I, Xba I, Hind II and Pst I. The results showed that the MSA-1 DNA had one Bg1 II site, one EcoR I site, two Xba I sites, one Hind II site and one Pst I site. The MSA-2 DNA had only one Hind II site. The surface antigen gene of P. malariae was little known. This result also showed that there was probably an analogue of P190 on the surface of P. malariae, and they might fall into two types. This study is informative for further investigation on malariae parasites. PMID- 2208631 TI - [Study on McAbs against protein "target antigen" in Schistosoma japonicum]. AB - In the studies presented here, we demonstrated the feasibility of producing large number of hybridoma cell lines secreting McAbs against S. japonicum including 16 cell lines secreting IgG McAbs (7 for IgG1, 5 for IgG2a, 1 for IgG2b, 3 for IgG3) and 13 McAbs for IgM, on the basis of successfully extracting 24-26kD and 90kD "target antigen" proteins known as important antigens for inducing schistosome protective immunity. All the above cell lines were characterized for localization of the McAbs, mediating in vitro ADCC against schistosomula, epitope recognized by the McAbs on different kinds of schistosome antigens. Studies have shown the evidences that the McAbs can be used to identify the "target antigen" on the surface of schistosome, to isolate and purify "target antigen" of S. japonicum by chromatography column bearing McAbs, as well as to immunize animals as antigens for accumulation of data in the development of vaccine against S. japonicum via anti-idiotype antibodies. PMID- 2208632 TI - [Studies on the strain differences of Schistosoma japonicum in the mainland of China. I. Compatibility between schistosomes and their snail hosts]. AB - Oncomelania hupensis hupensis from six localities were used in this study, i.e. Guichi of Anhui in the east, Jianli of Hubei in the middle, Guiping of Guangxi in the south, Tianquan of Sichuan and Eryuan of Yunnan in the southwest and Fuqing of Fujian in the southeast. Snails from each locality were individually cross exposed to 20 miracidia of the different isolates of S. japonicum from the above named places, with the exception of Fujian Province where no snail could be found naturally infected with S. japonicum. The results showed that snails from one locality were readily infected with the local isolate of S. japonicum. Besides, cross infection also took place readily between the snails and the schistosomes from Hubei and Anhui with snail infection rates of 43.8% and 40.9% respectively. Snails from Sichuan and Yunnan were refractory to infection with schistosome isolates from Hubei and Anhui, but the isolate from Sichuan was able to develop in Oncomelania snails from Hubei and Anhui, resulting in infection rates of 10.2% and 4.5% while that from Yunnan, in snails from Hubei and Anhui in infection rates of 33.6% and 10.8% respectively. Though the Guangxi isolate of S. japonicum developed readily in both Anhui (30.7%) and Guangxi snails (9.4%), the average precercarial period was 100.9 days in the former which was significantly longer than 76.9 days in the latter. None of the other snails from Sichuan, Yunnan and Fujian became infected. On the other hand, snails from Guangxi infected with Anhui parasites also had a longer precercarial period of 92.7 days compared with that of 81.6 days in Anhui snail.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2208633 TI - [Effect of albendazole and pyrantel in treating intestinal helminthiasis and controlling the recurrence of hookworm infections]. AB - A total of 720 human intestinal helminthic infections were divided into 4 groups and treated with albendazole 400mg/d x 3d, 400mg/d x 5d, pyrantel 1,500mg/d x 3d, or 1,500mg/d x 5d. Half a month after treatment, the negative rates of hookworm egg were 98.6, 98.6, 86.2 and 93.5%, those of ascaris egg were 96.5, 98.2, 92.9 and 96.3%, and those of whipworm egg were 86.4, 89.0, 68.9 and 67.0% respectively. Reduction rate of hookworm egg reached more than 98% in all the 4 groups. Six months after treatment, however, the positive rates of all the 4 groups rose again in varying degrees. The predominant species of hookworm infections was Necator americanus before the treatment and Ancylostoma duodenale after the treatment. It was demonstrated that the recurrence of hookworm infection resulted from A. duodenale infections, while a single dose of 400mg albendazole per day for 3 or 5 days showed good effect in controlling the recurrence of hookworm infections in a certain area. PMID- 2208634 TI - Long day lengths enhance myelination of midbrain and hindbrain regions of developing meadow voles. AB - Rates of brain growth differed in meadow voles maintained in long (LP) or short (SP) photoperiods postnatally. At 35 days of age, brain weight was greater by 6.6% in LP males and by 4.7% in LP females as compared to their SP counterparts. Whole brain galactolipid content, an index of brain myelin, was greater by 15.6% in LP as compared to SP males. At 70 days of age, brains of LP males were 4% heavier than those of SP males. Differences attributable to photoperiod were most pronounced in midbrain and hindbrain (8% and 14%, respectively). DNA and galactolipid contents were greater by 11% and 15%, respectively, in hindbrain of LP males. Photoperiod did not affect any of these measures in diencephalon, striatum, or cerebellum. Short day lengths reduce myelination in meadow voles, presumably by decreasing proliferation rates of oligodendroglia. This is one facet of a general delay in somatic development associated with being born at the end of the normal breeding season when day lengths are decreasing or below a critical threshold. PMID- 2208635 TI - Inward rectifier potassium current on embryonic Xenopus muscle cells at different times in culture. AB - Whole cell current recordings of Xenopus muscle cells in 1-day-old cultures revealed an inward K+ current, with properties similar to the inward rectifier of adult muscle. However, at the earliest ages (less than 10 h in culture) the time dependent decline in the current amplitude, indicative of a depletion of extracellular K+, was not present. The change in the time-dependent decline of the current amplitude may result from a change in the channel itself or a change in the distribution of the channel in the membrane. PMID- 2208637 TI - An electrophysiological study of the ontogenesis of adenosine receptors in the CA1 area of rat hippocampus. AB - The depressant effect of adenosine (Ad) was studied electrophysiologically in hippocampal slices from 5-, 10-, 15-, 20-, 30- and 120-day-old rats. Ad (10 microM) depressed the field EPSP in CA1 to the same extent in all age groups. Caffeine (Caf), an Ad receptor antagonist, enhanced and nitrobenzylthioinosine (NBI), an Ad uptake blocker, depressed the field EPSP. Both these effects were, however, less prominent in slices from younger animals, a finding consistent with lower extracellular levels of endogenous Ad in neonatal rats. PMID- 2208636 TI - The prevention of natural motoneuron cell death by dibutyryl-cyclic GMP in the spinal cord of White Leghorn chick embryos. AB - The effect of dibutyryl-cyclic guanosine monophosphate (db-cGMP) treatment of White Leghorn chick embryos on the extent of natural motoneuron cell death in the lumbar spinal cord was examined. A dose of 1.59 mumol of db-cGMP effected an increase in motoneuron survival of 26.7%. No effect on motoneuron survival was observed with equimolar doses of 8-bromo-cGMP, db-cAMP, GMP, guanosine, or butyric acid. PMID- 2208638 TI - 1,1,3 tricyano-2-amino-1-propene (Triap): a small molecule which mimics or potentiates nerve growth factor. AB - 1,1,3 Tricyano-2-amino-1-propene (Triap) is a small molecular weight compound which increases the rate of nerve and tissue regeneration in several experimental systems. Early experiments with this compound showed that, like nerve growth factor (NGF), Triap induced neurite formation in chick spinal ganglia. To assess the similarity between NGF and Triap, we compared the effects of Triap and NGF on a rat pheochromocytoma cell line (PC12) and on cell survival in a primary chick neuronal culture. In the latter, Triap at less than 0.01 nM preserved neurons and caused them to extend neurites as did 1 nM NGF. Triap induced neurite outgrowth in the PC12 cell line giving a maximal response (40-50% of the maximal response of NGF) at a concentration of 20 micrograms/ml (151 microM). Triap's morphological effects were not inhibited by antibodies directed against NGF or the NGF receptor. Low concentrations of Triap also potentiated the morphological effects of NGF. Triap induced an increase in cell-substratum adhesion and cellular hypertrophy in PC12 cells and also potentiated the adhesive actions of NGF. Triap had no effect on ornithine decarboxylase activity even though it potentiated NGF's effects on this enzyme. These data indicate that Triap induces neurotrophic effects and does not seem to act through the same mechanisms as NGF but can potentiate many of NGF's morphological and biochemical actions. PMID- 2208639 TI - Developmental changes in transferrin and iron uptake by the brain in the rat. AB - The uptake of transferrin and iron by the brain, liver and femurs was investigated in rats using 125I-59Fe-transferrin (Tf), and 131I-albumin in order to measure the plasma content of the organs. Measurements in rats ranging in age from birth to 70 days revealed that the rate of iron uptake by the brain increased rapidly over the first 15 days of life, peaking at 15 days and thereafter declining. A similar pattern occurred in the uptake of 125I-Tf. These changes were accompanied by rapid growth of the brain up to 15 days and a decrease in the concentration of non-haem iron. The turnover of 59Fe and 125I-Tf in the brain was also determined by measuring radioactivity in the brain of 15 day rats at various times after injection from 15 min to 13 days. The amount of 59Fe in the brain increased over the first 4 h and thereafter remained constant. By contrast, the 125I-Tf values increased rapidly during the first 15 min to reach a relatively constant level which was maintained for at least 6 h after which it declined. The patterns of uptake by the brain were different from those found in the liver and femurs, indicating that the changes in the brain were specific for that organ.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2208640 TI - Development of the rat corticospinal tract through an altered glial environment. AB - The major corticospinal tract (CST) in the rat is located at the base of the dorsal funiculus. It is a late-developing tract, and the growth of its axons into the lumbosacral region of the spinal cord does not occur until postnatal days 5 and 6. This delay is taken advantage of in this study in order to evaluate the effects of a markedly reduced glial population on ingrowth of the CST axons into the lumbosacral spinal cord. A reduction of the glial population is achieved by exposure of this region of spinal cord to X-radiation at 3 days of age. Growth of CST axons into and through the lumbosacral spinal cord in rats in which this region has undergone a radiation-induced depletion of glial cells is compared with that in their non-irradiated littermate controls by axonal tracing techniques using horseradish peroxidase (HRP). The HRP was applied directly to the motor cortices of normal and irradiated rats, and at all ages studied, there was anterograde filling of CST axons and their growth cones. At 3 days postnatally, the age when the lumbosacral spinal cord was irradiated in the experimental animals, CST axons were present in the more rostral thoracic levels. CST axons were observed in the lumbar region of non-irradiated rats on day 5, and by day 7 they were present at sacral levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2208641 TI - Effects of early postnatal receptor damage on development of gustatory recipient zones within the nucleus of the solitary tract. AB - The temporal correspondence between neuroanatomical and neurophysiological development of peripheral and central gustatory neurons has suggested that morphological development of the first-order central gustatory relay, located in the rostral nucleus of the solitary tract (NST), may be dependent on afferent input from peripheral gustatory pathways. The objective of the present study was to determine the effects of perinatal receptor damage on development of gustatory recipient zones within the rostral and intermediate NST. Results show that damage induced to fungiform receptors of the anterior tongue at postnatal day 2 (P2) alters normal development of NST terminal fields associated with the chorda tympani nerve (CT) and greater superficial nerve (GSP), and that alterations in the CT/GSP terminal field persist in adulthood after peripheral gustatory receptors have regenerated. Damage induced to fungiform receptors at P2 does not alter the normal development of glossopharyngeal terminal fields in the intermediate NST. Receptor damage produced at P10 and P20 is without effect on normal development of the CT/GSP terminal field. Thus, fungiform receptor damage at P2 produces specific alterations in the development of NST terminal fields that receive projections from the facial-intermediate nerve, and receptor damage effects are only obtained during a critical period of postnatal development. P2 receptor damage has the overall effect of eliminating caudally directed migration of CT/GSP axons to additional projection neurons that establish connections with the second-order central gustatory relay located in the parabrachial nucleus (PBN). Behavioral studies were conducted to determine the functional consequences of early receptor damage. Results from behavioral studies show that bilateral damage to fungiform papillae at P2 alters normal adult preferences to low and intermediate concentrations of NaCl and sucrose tastes, yet aversions to citric acid and quinine HCl are not obviously affected. Therefore, anatomical alterations in the CT/GSP terminal field produced by P2 receptor damage are accompanied by specific changes in adult taste preference responses. PMID- 2208642 TI - The development of radial glia and radial dendrites during barrel formation in mouse somatosensory cortex. AB - The development of the mouse barrel field (the mystacial whisker representation in SI cortex) was examined using immunocytochemical probes for radial glia and neuronal dendrites. The maturing dendrites were revealed using antibodies against microtubule-associated protein 2 (MAP2) and the radial glia were demonstrated with a recently described monoclonal antibody, RC2. By postnatal day 7 both antibodies clearly demonstrated a non-uniform distribution of dendrites and glia that was unique to layer IV of the barrel field. Both MAP2-immunoreactive dendrites and RC2-immunoreactive radial glial fibers were dense near the walls (sides and septae) of barrels than near the hollows (centers) of barrels. In contrast, in other cortical regions, radial glia and dendrites did not appear obviously patterned. Not until postnatal day 4 did the pattern of both radial glial fibers and apical dendrites begin to emerge in a barrel-like distribution. We conclude that the non-uniform distribution of radially oriented dendrites and radial glial fibers appears with a similar developmental time course to that described for the appearance of the cellular barrels themselves. PMID- 2208644 TI - Measuring iron-dextran in serum: is it important? PMID- 2208643 TI - Localization of morphologically distinct microglial populations in the developing human fetal brain: implications for ontogeny. AB - Although 70 years have elapsed since del Rio Hortega's initial description of microglia, the ontogeny of these cells remains enigmatic. In addition to the general scientific importance of clarifying this issue, a more complete characterization of microglia is dictated by their apparent pivotal role in the pathophysiology of central nervous system (CNS) disease associated with the acquired immunodeficiency syndrome (AIDS) in adults and, especially, in children. To accomplish this goal, fetal central nervous system tissue was collected at the time of elective pregnancy terminations. Coronal vibratome sections of Bouin's fixed cerebrum were either stained with Ricinus communis agglutinin-1 (RCA-1) or analyzed by immunohistochemistry using monoclonal antibodies that recognize human tissue macrophages and microglia. By at least 13 weeks of gestation, microglia were detected in fetal brain. In the 13-18 week gestational age cerebrum, there was variability in the morphology of microglia within the developing white matter and cortex. However, there was less variability within these areas in the 19-24 week gestational age group. At all ages the greatest number of labeled cells per field was in the germinal matrix with decreasing numbers in the developing white matter and cortex. Cells in the germinal matrix were round with short processes ('ameboid microglia') while cortical cells were more ramified ('resting microglia'). These results suggest that microglia may originate in the germinal matrix rather than in the pial mesenchyme as originally hypothesized by del Rio Hortega.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2208645 TI - Quality management science in clinical chemistry: a dynamic framework for continuous improvement of quality. AB - Current quality assurance approaches will not be adequate to satisfy the needs for quality in the next decade. Quality management science (QMS), as evolving in industry today, provides the dynamic framework necessary to provide continuous improvement of quality. QMS emphasizes the importance of defining quality goals based on the needs and expectations (implied needs) of customers. The laboratory can develop customer-friendly goals and measures of quality by recognizing that customers' experiences are represented by a totality of results. Quality goals and measures are best communicated as "total performance" by specifying a limit and percentile of the distribution, rather than a mean and standard deviation. Application of quality goals within the laboratory will usually require partitioning the total performance goal into components and translating those components into specifications to guide the operation and management of production processes. QMS also extends beyond technical processes to people processes and provides guidance for improving the quality of worklife and caring for the laboratory's most essential resource--our people. PMID- 2208646 TI - The relation of clinical catastrophes, endogenous oxalate production, and urolithiasis. AB - A dose-related toxicity syndrome of renal, cerebral, and liver dysfunction; metabolic acidosis; and deposition of calcium oxalate crystals in tissues is reported in association with various apparently unrelated treatments for a wide range of diseases. The parenteral nutrient xylitol, the hyperosmolar agent glycerol, the polysorbate emulsifiers (e.g., in vitamin E preparations), the anesthetic methoxyflurane, and possibly the experimental hypoglycemic agent dichloroacetate all produce a toxicity syndrome very similar to that of ethylene glycol poisoning. In long-term, high-dose oral toxicity studies with rodents, these or similar agents also produce calcium oxalate bladder stones and bladder tumors. Studies with both unlabeled and labeled agents in humans and animals and in vitro experiments with purified enzymes, tissue homogenates, and isolated hepatocytes have provided both strong circumstantial and direct evidence for the existence of minor pathways of carbohydrate metabolism and of oxidative dealkylation and dehalogenation reactions in drug biotransformations that link these agents to endogenous oxalate production. Because urinary oxalate is now considered to be a critical factor in stone formation and because it is increasingly accepted that 80-90% of urinary oxalate is produced endogenously, it is now possible to formulate pathways that link oxalate production with dietary macronutrients. Therapeutic modifications of diet, in vivo hormonal milieu, and intracellular metabolic controls in relation to endogenous oxalate production may provide new forms of treatment for urolithiasis. PMID- 2208647 TI - Frequency of the delta Phe508 mutation and correlation with XV.2c/KM-19 haplotypes in an American population of cystic fibrosis patients: results of a collaborative study. AB - The cystic fibrosis (CF) gene has been recently cloned, and a deletion of 3 basepairs (bp) of DNA was found on most of the CF chromosomes. This deletion leads to the synthesis of a protein that lacks a phenylalanine residue at position 508. Using two polymerase chain reaction protocols to study the frequency of this mutation in a series of 192 CF patients, we found the mutation on 72% of affected chromosomes. We then used this value to calculate the predictive value of a negative test result in a population-based screening program for CF carrier status. Haplotype analysis with the polymorphic markers XV.2c and KM-19 on 239 CF chromosomes revealed that 90.7% of CF chromosomes with the deletion had a single haplotype. This haplotype was also associated with 60.4% of CF chromosomes with unknown mutations. These values can be used to calculate the probability of whether an individual from the general population is a carrier of any CF mutation. PMID- 2208648 TI - Colorimetric liposome lysis for assay of anti-streptolysin O antibody. AB - We developed an automated colorimetric assay based on liposome lysis for measurement of the titer of anti-streptolysin O antibodies (ASO) in human sera by using liposomes in which alkaline phosphatase (EC 3.1.3.1) was entrapped. The assay involved the inhibition by ASO of liposome lysis caused by streptolysin O. The procedure was fully automated for use with a routine clinical automated analyzer. The inter- and intra-assay precision showed that results were reproducible. Potential interfering substances such as bilirubin, hemoglobin, and triglycerides did not affect the results. With this assay, results correlated well with those by the Rantz-Randall method and the latex agglutination method (r = 0.900 and 0.890, respectively). This automated colorimetric assay for ASO should be of use for diagnosing streptococcal infections. PMID- 2208649 TI - Ascorbic and dehydroascorbic acids measured in plasma preserved with dithiothreitol or metaphosphoric acid. AB - We describe a rapid method for accurately and precisely measuring ascorbic acid and dehydroascorbic acid in plasma. Total analysis time is less than 10 min, replicate analyses of a single pool provide precision less than or equal to 2%, and values measured in supplemented samples agree with known concentrations of 4.68 and 11.83 mg/L. The stability and homogeneity of lyophilized plasma samples supplemented with ascorbic acid and dithiothreitol are documented. We also describe a procedure in which metaphosphoric acid (50 g/L) is used to prepare a reference material for the measurement of ascorbic acid and dehydroascorbic acid. The procedure for both acids consists of first measuring the native ascorbic acid, then reducing the dehydroascorbic acid, at neutral pH, with dithiothreitol, and finally measuring the total ascorbic acid; dehydroascorbic acid is then determined by difference. The metaphosphoric-acid-treated samples were stable at 70 degrees C, but stability decreased with temperature over the range examined, 4 50 degrees C. PMID- 2208650 TI - A model for molecular screening of newborns: simultaneous detection of Duchenne/Becker muscular dystrophies and cystic fibrosis. AB - Gene mutations responsible for the majority of Duchenne/Becker muscular dystrophy (DMD/BMD) and cystic fibrosis (CF) chromosomes have been identified. We describe a DNA-based strategy, rather than the traditional biochemical assays, for screening newborns. DNA sequences spanning the CF mutation and several DMD/BMD deletion-prone exons are amplified simultaneously via a multiplex polymerase chain reaction. The gel is visually inspected for DMD/BMD deletions and then blotted and hybridized with allele-specific oligonucleotides to determine the presence or absence of the CF mutation. We determined that blood spots provide sufficient DNA for the molecular analysis, so the procedure can be used in screening programs of newborns. PMID- 2208651 TI - Improved methods for genotype determination of human alcohol dehydrogenase (ADH) at ADH 2 and ADH 3 loci by using polymerase chain reaction-directed mutagenesis. AB - The human gene for producing alcohol dehydrogenase (ADH; EC 1.1.1.1) is polymorphic at ADH 2 and ADH 3 loci. Until now, the study of this polymorphism required liver biopsy or allele-specific radioactive probes. We have used directed mutagenesis by the polymerase chain reaction (PCR) to amplify and analyze the genotype of ADH 2 and ADH 3 loci. Thus, we could determine easily and unambiguously the complete genotype at these two loci by using a microsample of blood and restriction fragment length polymorphism after DNA amplification by PCR. PMID- 2208652 TI - Sensitive salivary estradiol assay for monitoring ovarian function. AB - Measurement of steroids in saliva has excited interest because of the numerous potential clinical applications; noninvasive, convenient sampling; and apparently accurate reflection of the concentrations of physiologically active unbound steroid in the circulation. Although assays of saliva for several steroid hormones are available and widely used, assays for salivary estradiol are not, primarily because of methodological limitations. By modifying a commercially available kit for serum estradiol, our laboratory has developed a procedure that is sensitive, highly specific, and reliable for measuring salivary estradiol. Assay sensitivity is 0.5 fmol (0.14 pg; sample concentration 1.3 pmol/L) with a mean interassay CV of 10.8% at low concentrations. Clinical studies showed that values for serum and saliva are highly correlated (P less than 0.001), and demonstrated reliable detection of estradiol peaks during normal ovulatory cycles in serial samples from 15 women. Salivary estradiol peaked at 5.4 (SD 1.9) pmol/L on cycle day 14.4 (SD 3.2), 1.2 (SD 0.8) days before ovulation detected by ultrasound. This assay may be particularly helpful in investigating ovarian function and free estradiol in women at various stages of the reproductive cycle. PMID- 2208653 TI - Time-resolved fluoroimmunoassay for unconjugated estrogen in urine: comparison with a fluorometric assay for total estrogen and application in an in vitro fertilization program. AB - A time-resolved fluoroimmunoassay (TR-FIA) for unconjugated estrogens in human urine is described. 6-Keto-17 beta-estradiol-6-(O-carboxymethyl)oxime:bovine serum albumin is immobilized onto microtiter strip wells and the coated wells are incubated with 17 beta-estradiol standard preparations or unknowns with a polyclonal antiserum to 17 beta-estradiol-16,17-monosuccinyl:albumin. The antiserum-bound estrogen is detected by incubation with a europium-labeled anti rabbit IgG that serves as both second antibody and tracer. After the immunoreactions, the bound portion of the labeled antiserum is quantified by dissociating the Eu3+ in a fluorescence-enhancement solution and measuring its fluorescence with a time-resolved fluorometer. The detection limit of the TR-FIA is 24 pmol of 17 beta-estradiol per liter; the analytical range extends to 1.8 nmol/L. This assay is a convenient alternative to radioimmunoassay and to the automated Kober-Ittrich fluorometry of total estrogen. Its advantages include short counting times; use of nonradioactive, stable reagents, all of which are commercially available; and more nearly complete automation. We conclude that this TR-FIA, compared with the Kober-Ittrich fluorometric assay (J Endocrinol 1957; 16:49-56), provides the clinician with equivalent information during follicular development therapy as part of an in vitro fertilization program. PMID- 2208654 TI - Erythrocyte porphobilinogen deaminase activity in porphyria cutanea tarda. AB - Porphyria cutanea tarda (PCT) results from a metabolic block in heme synthesis at the level of uroporphyrinogen decarboxylase. We measured the activity of one of the enzymes preceding it in the heme biosynthetic pathway, porphobilinogen deaminase (PBGD; EC 4.3.1.8), in erythrocytes of 47 patients with symptomatic or asymptomatic familial or sporadic PCT. PBGD activity was significantly increased in all four PCT groups, compared with controls. To study the mechanism of this increased PBGD activity, we determined, using polyclonal antibodies, the amount of immuno-detectable PBGD per 100 units of PBGD activity (Ig PBGD/100 U) and the total amount of immuno-detectable PBGD (Ig PBGD) in erythrocytes from all 47 patients and from controls. In both familial and sporadic PCT, Ig PBGD/100 U was decreased compared with that in controls (P less than 0.05). Especially in asymptomatic patients of the familial PCT group there was an inverse correlation between increasing PBGD activity and Ig PBGD/100 U (r = -0.90). In familial PCT, and to a minor degree in sporadic PCT, an increase in PBGD activity was accompanied by an increased Ig PBGD, compared with controls (familial PCT: P less than 0.001, sporadic PCT: P less than 0.05). In familial and sporadic PCT an increase in erythrocyte PBGD activity can, at least partly, be explained by a diminished degradation of PBGD. In familial PCT, in the symptomatic group more than in the asymptomatic group, and to a minor degree in sporadic PCT, there is in addition an increase in the absolute amount of PBGD. PMID- 2208655 TI - Mass concentration of creatine kinase MB isoenzyme and lactate dehydrogenase isoenzyme 1 in diagnosis of perioperative myocardial infarction after coronary bypass surgery. AB - Recent advances in methodology allow the mass concentration of creatine kinase MB isoenzyme (CK-MB), and of lactate dehydrogenase isoenzyme 1 (LD1) to be determined quickly and easily as routine, emergency tests. We evaluated these tests as diagnostic criteria of perioperative myocardial infarction (PMI) after coronary bypass surgery. These tests were compared with the usual measurements of CK-MB activity by immunoinhibition and LD1 by electrophoresis and with other biological markers of myocardial infarction such as total CK, total LD, and aspartate aminotransferase. Sixty-one patients who underwent coronary bypass grafting were followed pre- and postoperatively by enzyme determinations and electrocardiography; a subgroup was monitored by myocardial scintigraphy. CK-MB mass appeared to be the best marker of PMI during the first 48 h, although LD1 was the marker of choice from days 2 to 4. PMID- 2208656 TI - Measurement of polyethylene glycol 400 in urine by direct-injection high performance liquid chromatography. AB - We describe a new "high-performance" liquid chromatographic (HPLC) method for estimating polyethylene glycol 400 (PEG 400) in urine. Direct injection of diluted urine samples onto the column eliminates the necessity for lengthy preparative steps, resulting in considerable saving of both time and chemicals. High analytical recoveries (94-102%) and a rapid rate of analysis are achieved. Results vary linearly with concentrations from 0.2 to 1.6 g/L and the six major components can be individually quantified precisely at all concentrations in this range. This method shows better sample recovery, sensitivity, and reproducibility than does a previously described method. The increased sensitivity should allow the use of lower oral doses of polyethylene glycol 400 in future studies of intestinal permeability. PMID- 2208657 TI - Colorimetry and constant-potential coulometry determinations of transferrin-bound iron, total iron-binding capacity, and total iron in serum containing iron dextran, with use of sodium dithionite and alumina columns. AB - After the parenteral administration of iron-dextran (imferon), the increased total iron concentrations in serum can be determined by atomic absorption spectroscopy and by colorimetric methods involving sodium dithionite, which reductively dissociates iron from the dextran complex. We report that constant potential coulometry detects only about 55-70% of dextran-bound iron before dithionite reduction and variable amounts after reaction with the reducing agent. In addition, we have developed a procedure for determining transferrin-bound iron, total iron-binding capacity (TIBC), total iron, and dextran-bound iron with the Kodak Ektachem colorimetric system. In determining total serum iron, the sample is first mixed with sodium dithionite, which rapidly dissociates all dextran-bound iron, but does not remove iron from either transferrin or hemoglobin. After the mixture is applied to an Ektachem slide, transferrin-bound iron is released at pH 4 and is detected together with the iron previously bound to dextran. TIBC is determined by mixing serum with ferric citrate in moderate excess and filtering through a small alumina (Al2O3) column, which binds excess free iron and iron-dextran; the iron in the column eluate represents the TIBC. Transferrin-bound iron is determined by applying diluted serum without added ferric citrate to an alumina column and measuring the iron in the column eluate. Dextran-bound iron is equivalent to the difference between total and transferrin bound iron. Using this method, we found that transferrin iron-binding sites are saturated in vitro by excess iron-dextran less efficiently than by ferric citrate. PMID- 2208658 TI - Spontaneous decay of oxidized ascorbic acid (dehydro-L-ascorbic acid) evaluated by high-pressure liquid chromatography. AB - We applied high-pressure liquid chromatography to assess the decomposition of the oxidized form of vitamin C, dehydro-L-ascorbic acid. We selected experimental conditions that might represent a wide variety of clinical and research procedures. Decay of dehydro-L-ascorbic acid proceeded much more rapidly at high pH (7-8) than at low pH (3-5) and was more rapid at 37 or 45 degrees C than at 0 or 23 degrees C. When evaluated at pH 6.6, the percent decay was somewhat more rapid from an initial concentration of 1000 mumol/L than at 5-10 mumol/L. The analytical procedure (HPLC) provided useful information about the rate of decay under various conditions. This may facilitate future biological and clinical studies that require a distinction between the oxidized and reduced forms of vitamin C. PMID- 2208659 TI - Evaluation of the clinical usefulness of a chemiluminometric method for measuring creatine kinase MB. AB - The use of creatine kinase isoenzymes (CK-MB) in the diagnosis of acute myocardial infarction (AMI) is well established. We evaluated the use of a new chemiluminometric method (CK-Ciba) for measuring CK-MB by calculating its sensitivity, specificity, positive and negative predictive values, and diagnostic efficiency for diagnosing AMI. We tested 633 samples from 229 patients within 4 h of receipt. The patients were divided into four groups: (1) patients who had an AMI, (2) patients who had AMI ruled out, (3) patients who had CK-MB measured for reasons other than to rule out AMI, and (4) patients who had only one sample drawn. Only patients in Groups 1 and 2 were used in the study. AMI was diagnosed by a cardiologist. The prevalence of AMI in our population was 0.18. A receiver operator characteristic curve was used to establish optimal values for identifying AMI with the CK-Ciba results: CK-MB greater than or equal to 10 micrograms/L and a CK-MB index of greater than or equal to 3.0 (micrograms of CK MB per U of CK x 100). Using these values, we calculated a sensitivity of 1.00, specificity of 0.97, positive predictive value of 0.87, negative predictive value of 1.00, and a diagnostic efficiency of 0.97. We conclude that the CK-Ciba method has high sensitivity, high specificity, and good predictive values for CK-MB and is appropriate to use to rule out AMI. PMID- 2208660 TI - Iron and total iron-binding capacity in serum of patients receiving iron-dextran: Kodak Ektachem methodologies, spectrophotometry, and atomic-absorption spectrometry compared. AB - We compared the analytical performance of the Kodak Ektachem XR700 assays of iron (Fe) and total iron-binding capacity (TIBC) with that of a conventional ferrozine assay (performed with a Cobas-Bio) and occasionally with that of atomic absorption spectrometry (AAS). The correlation was modest between Kodak and Cobas Bio concentrations of Fe in serum (r = 0.79). Multiple outliers were noticed in samples from hemodialysis patients, with Cobas values exceeding those of Kodak by as much as 26 mumol/L. These intermethod differences were not dissipated by dialysis, but were invariably accompanied by an even higher total Fe content of the serum as judged by AAS (20 to 80 mumol/L higher). TIBC values by Kodak and Cobas-Bio were highly correlated (r = 0.99); again, the Cobas-Bio results exceeded those by Kodak in some hemodialysis patients, but always for samples with higher Fe concentrations by the Cobas-Bio. By AAS, the TIBC values of these patients also exceeded those by Kodak, to about the same extent as observed for serum Fe. These intermethod differences in Fe and TIBC were seen only in patients who had received an intravenous Fe-dextran (Imferon) injection two to three days before blood sampling but could be generated in vitro by adding Imferon to serum from normal controls. Less than 6% of dextran-bound Fe is measured as Fe by Kodak, as opposed to 20-30% by Cobas-Bio and 89-120% by AAS. We conclude that the Kodak Fe slides are superior to liquid reagents, by exclusively measuring protein bound circulating Fe pools. PMID- 2208661 TI - Improved method for identifying alpha 1-antitrypsin Pi M subtypes by isoelectric focusing in agarose. AB - We describe an improved method for the classification of alpha 1-antitrypsin variants by isoelectric focusing in agarose. Identification of the three Pi M subtypes can now be made by using a narrow-range carrier ampholyte (pH 4.2-4.9) and pretreating serum with dithioerythritol-iodoacetic acid to enhance band resolution. Phenotype results for two groups of Pi M homo- and heterozygotes are compared to illustrate the improved accuracy of the new method. PMID- 2208662 TI - Clinical evaluation of an automated chemical inhibition assay for lactate dehydrogenase isoenzyme 1. AB - We evaluated an automated assay for lactate dehydrogenase (LD; EC 1.1.1.27) isoenzymes, supplied by Boehringer Mannheim Diagnostics (BMD) and based on selective chemical inhibition of non-LD-1 isoenzymes by guanidine thiocyanate. Results were compared with the Roche Isomune LD-1 method. The Hitachi 717 analyzer was used to measure enzyme activity for both procedures in 229 serum samples. One hundred specimens were also analyzed by the Helena rapid electrophoresis (REP) method. We determined the limit of linearity of the BMD method to be about 1200 U of LD-1 per liter. The analytical correlation of BMD (y) with Isomune (x) yielded y = 1.0x + 0.5 U/L, r = 0.997, Sy/x = 16.9 (range 20 1397 U/L). The regression equation for BMD vs REP was y = 1.1x + 7.2% (r = 0.800, Sy/x = 7.4, range 14-83%). Average values for within-run precision for low (38 U/L), medium (180 U/L), and high (865 U/L) controls were 4.1%, 1.0%, and 0.5%, respectively (16 trials of six each). The average values for run-to-run precision were 4.1%, 1.7%, and 1.1%, respectively, for these controls (n = 16). We used receiver-operating characteristic curves to determine optimum decision limits. Using an LD-1 cutoff of 40% of total LD, we obtained a clinical sensitivity of 97 100% and a specificity of 95% when blood was collected during the optimum interval, 24-48 h after the onset of chest pain. We conclude that the BMD LD-1 assay is equivalent to the immunochemical and electrophoretic assays for measuring the LD-1 isoenzyme. PMID- 2208663 TI - Deuterium enrichment of plasma determined by nuclear magnetic resonance spectroscopy: dilution kinetics of 2H2O and estimation of total body water. AB - We demonstrate the feasibility of quantifying the abundance of 2H in plasma by nuclear magnetic resonance (NMR) spectroscopy. After adding internal standard (tert-butyl-d9 alcohol) to deproteinized plasma samples containing 2H2O, we determined the ratio of NMR peak areas for 2H2O and tert-butyl-d9 alcohol. This peak-area ratio was directly proportional to the exogenous 2H enrichment of plasma (difference between measured and naturally occurring 2H) between 0 and 0.272 atom % (r = 0.999). The coefficient of variation was 1.34% at an exogenous enrichment of 0.136 atom %. We applied this method to a study of the dilution kinetics of 2H2O to determine the optimal time and method of blood sampling for estimation of total body water content. The 2H enrichment of plasma stabilized by 4 h after intravenous injection of 2H2O, 1 g/kg of body weight, and fluctuated within 2-4% of the 4- to 8-h mean thereafter. PMID- 2208665 TI - A kinetic assay for urea in undiluted urine specimens. AB - We describe a kinetic assay for quantifying urea in undiluted urine samples. The assay linearity extends to urea concentrations of 400 mmol/L, is free from interference from blood (10 mL/L) or bilirubin (1 mmol/L), is sufficiently precise for routine use, and correlates well with an established method for assay of diluted urine samples. PMID- 2208664 TI - Automated fructosamine assay with improved accuracy used to quantify nonenzymatic glycation of serum proteins in diabetes mellitus and chronic renal failure. AB - We optimally solubilized the diformazan that forms during the fructosamine reaction with a nonionic detergent; we then automated the assay. After optimal solubilization of diformazan, we found that serum urate contributed significantly to the color formation in fructosamine reaction. When the error introduced by urate was corrected mathematically by use of an experimental determined factor, the serum fructosamine concentrations obtained were comparable with those of a more specific test of the nonenzymatic glycation (HPLC of hydrolyzed proteins). We found that concentrations of fructosamine in serum increased with increasing age of subjects. In diabetic patients the average concentration of fructosamine in serum exceeded that in nondiabetic subjects and correlated with the preprandial serum glucose and with other measures of deteriorating glycemic control (e.g., increased need for insulin therapy). Serum fructosamine normalized for albumin content was also increased in patients with chronic renal failure. Multiple mechanisms (including exposure of patients to hypertonic glucose during dialysis) appear to be involved in the increase of serum fructosamine in patients with chronic renal failure. PMID- 2208666 TI - Canadian Consensus Meeting on cyclosporine monitoring: report of the consensus panel. PMID- 2208668 TI - Effect of heat treatment on plasma aminotransferases. PMID- 2208667 TI - Diagnostic accuracy of Kodak creatine kinase MB, Stratus creatine kinase MB, and lactate dehydrogenase isoenzyme 1 in serum after acute myocardial infarction. PMID- 2208669 TI - HPLC of urinary catecholamines in the presence of labetalol, captopril, and alpha methyldopa. PMID- 2208670 TI - Lipid-peroxidation products and antioxidants in plasma of cigarette smokers. PMID- 2208671 TI - Improved detection, via ISO-DALT two-dimensional electrophoresis, of "low Z expressor" individuals with alpha 1-antitrypsin MZ phenotype. PMID- 2208673 TI - Bilirubin interference in determinations of creatinine with the Hitachi 737 analyzer. PMID- 2208672 TI - Purification of DNA from clotted blood. PMID- 2208674 TI - Cardiac troponin T identifies unspecific increases of CKMB after physical exercise. PMID- 2208675 TI - A specific radioimmunoassay for cyclosporine? PMID- 2208676 TI - Comparing the "sensitivity" of thyrotropin assays by using between-run precision profiles. PMID- 2208677 TI - Zero-bias cholesterol and triglyceride proficiency survey. PMID- 2208679 TI - Consider lipoprotein(a), not just apolipoprotein B, when determining low-density lipoprotein for lipoprotein profiles. PMID- 2208678 TI - Skewness and quality-control procedures. PMID- 2208680 TI - Evaluation of abbott IMx CK-MB immunoassay. PMID- 2208682 TI - Ethylene glycol quantification: avoid propylene glycol as an internal standard. PMID- 2208681 TI - Plasma factor(s) inhibiting cell magnesium efflux rapidly determined with a biological assay. PMID- 2208683 TI - Robotics in the medical laboratory. AB - Robotic systems specifically designed for the automation of laboratory tasks are now available commercially. Equipped with computer, analytical hardware, and supporting software, these devices may soon revolutionize the concept of the clinical laboratory and usher in a new era in laboratory testing. We review the types of robots and motion-control software currently available and discuss examples of their applications that extend across many analytical areas. Several ongoing projects are concerned with the systematic integration of robotic devices with other laboratory automation. The integrated robotic laboratories emerging from this work portend a bright future for robotic automation. Many challenges remain, however, in training the individuals needed to develop and manage robotic laboratories, and in making this new technology cost-efficient. PMID- 2208684 TI - Robotic transportation. AB - Mobile robots perform fetch-and-carry tasks autonomously. An intelligent, sensor equipped mobile robot does not require dedicated pathways or extensive facility modification. In the hospital, mobile robots can be used to carry specimens, pharmaceuticals, meals, etc. between supply centers, patient areas, and laboratories. The HelpMate (Transitions Research Corp.) mobile robot was developed specifically for hospital environments. To reach a desired destination, Help-Mate navigates with an on-board computer that continuously polls a suite of sensors, matches the sensor data against a pre-programmed map of the environment, and issues drive commands and path corrections. A sender operates the robot with a user-friendly menu that prompts for payload insertion and desired destination(s). Upon arrival at its selected destination, the robot prompts the recipient for a security code or physical key and awaits acknowledgement of payload removal. In the future, the integration of HelpMate with robot manipulators, test equipment, and central institutional information systems will open new applications in more localized areas and should help overcome difficulties in filling transport staff positions. PMID- 2208685 TI - Automated blood-sample handling in the clinical laboratory. AB - The only significant advances in blood-taking in 25 years have been the disposable needle and evacuated blood-drawing tube. With the exception of a few isolated barcode experiments, most sample-tracking is performed through handwritten or computer-printed labels. Attempts to reduce the hazards of centrifugation have resulted in air-tight lids or chambers, the use of which is time-consuming and cumbersome. Most commonly used clinical analyzers require serum or plasma, distributed into specialized containers, unique to that analyzer. Aliquots for different tests are prepared by handpouring or pipetting. Moderate to large clinical laboratories perform so many different tests that even multi-analyzers performing multiple analyses on a single sample may account for only a portion of all tests ordered for a patient. Thus several aliquots of each specimen are usually required. We have developed a proprietary serial centrifuge and blood-collection tube suitable for incorporation into an automated or robotic sample-handling system. The system we propose is (a) safe--avoids or prevents biological danger to the many "handlers" of blood; (b) small--minimizes the amount of sample taken and space required to adapt to the needs of satellite and mobile testing, and direct interfacing with analyzers; (c) serial--permits each sample to be treated according to its own "merits," optimizes throughput, and facilitates flexible automation; and (d) smart--ensures quality results through monitoring and intelligent control of patient identification, sample characteristics, and separation process. PMID- 2208686 TI - Integrating laboratory robots with analytical instruments--must it really be so difficult? AB - Creating a reliable system from discrete laboratory instruments is often a task fraught with difficulties. While many modern analytical instruments are marvels of detection and data handling, attempts to create automated analytical systems incorporating such instruments are often frustrated by their human-oriented control structures and their egocentricity. The laboratory robot, while fully susceptible to these problems, extends such compatibility issues to the physical dimensions involving sample interchange, manipulation, and event timing. The workcell concept was conceived to describe the procedure and equipment necessary to carry out a single task during sample preparation. This notion can be extended to organize all operations in an automated system. Each workcell, no matter how complex its local repertoire of functions, must be minimally capable of accepting information (commands, data), returning information on demand (status, results), and being started, stopped, and reset by a higher level device. Even the system controller should have a mode where it can be directed by instructions from a higher level. PMID- 2208687 TI - Laboratory robotics and artificial intelligence. AB - Intelligent robots, which incorporate artificial intelligence in their controlling software, are the next step in bringing the laboratory robot to its full potential. The areas currently under study in our laboratory are improved user interfaces for laboratory robotics, the integration of object-oriented databases into robot control programs, and strategies to optimize multi-step procedures. The ultimate goal of this work is the Standard Robotics Method. The Standard Robotics Method we envision would allow a robotic method to be transferred from one laboratory to another. PMID- 2208688 TI - A fully robotic assay for human hormone analysis. AB - To create a more convenient analytical system for the determination of hormones in human serum, we attempted to make a robotic system by combining robotic equipment and the DELFIA system (time-resolved fluoroimmunoassay; Pharmacia Co.). To combine the two systems, we constructed various peripheral instruments, created software for the computer, and introduced these to the robot at our laboratory. We developed this system to operate more exactly and smoothly than manual procedures during analytical movement steps such as taking samples, adding reagents, mixing samples in kit strips, and measuring the results of the fluoroimmunoassay. With this system the robot can measure in random sequence eight hormones--thyrotropin, triiodothyronine, thyroxin, prolactin, lutropin, follitropin, choriogonadotropin, and cortisol--according to physicians' orders placed through the computer. Consequently, this robotic system can operate fully automatically, from delivering the samples into the robotic system to printing out graph reports for physicians. The technologist merely puts the sample rack on the conveyor belt. PMID- 2208689 TI - A standard clinical instrument interface for robotic applications. AB - Many clinical laboratory instruments are not designed for robotic compatibility, hence the need for standardization of data communications and analyzer interface hardware. We developed an interface with supporting software that simplifies communication between a microcomputer and clinical instruments. Our interface establishes a standardized bidirectional communications protocol, which is useful in many clinical laboratory robotic projects. Instruments targeted for interfacing require no prior on-board communications capabilities. Additionally, modifications to the clinical instrument are minimized. Once installed, the interface translates input commands to codes or actions recognizable by the analyzer. Features not normally available to the user, such as electrode real time response and full instrument status, are also reported by the interface, thereby establishing a remote monitor and control mechanism for the interfaced instrument. We have written an operating system to control the interface microcomputer, which in turn commands and monitors the clinical analyzer. A host computer controls the information flow to the interface and provides (a) requests to the interface for instrument operation and status and (b) commands to the interface to initiate the desired instrument operation. This arrangement maintains complete instrument functionality as designed by the manufacturer while allowing remote monitoring and operation of the instrument. PMID- 2208690 TI - A systematic approach to materials handling in clinical laboratories. AB - I describe the automation/mechanization of several areas of sample processing at SmithKline Beecham Clinical Laboratories. By analyzing and implementing new systems for conveyance and sorting of incoming specimens, specimen processing, within-laboratory specimen delivery, specimen storage and retrieval, and client resupply, we greatly improved the productivity of the nontechnical aspects of laboratory operations. PMID- 2208691 TI - Application of existing technology to meet increasing demands for automated sample handling. AB - As the clinical laboratory advances toward total automation, the marketplace is now demanding more-efficient sample-handling systems. These demands have arisen over a relatively short period of time, in part because of heightened concern over laboratory safety and the resulting manpower shortages. Adding sample handling capabilities to existing instrumentation is often a challenge, because usually mechanical or system constraints are present that interfere. This challenge has been overcome in the DuPont Sample Management System (SMS), a second-generation general chemistry analyzer that incorporates the latest barcode and computer-interfacing technology. The development of the SMS system relies heavily on recent advances in technology, e.g., software modeling and computer aided design. The SMS system includes a barcode scanner based on "charge-coupled device" technology, a random-access sample wheel, and new software that oversees the various functions. PMID- 2208692 TI - Consideration of laboratory parameters in design and implementation of automated systems with barcoding. PMID- 2208693 TI - Use of serum blank information to quantify chromogenic interferents and correct sensitive analyses. PMID- 2208695 TI - Considerations in the design and implementation of user interfaces between laboratory instrumentation and laboratory information systems. PMID- 2208694 TI - One-step chromatographic immunoassay for qualitative determination of choriogonadotropin in urine. PMID- 2208696 TI - Automated system for positive specimen identification and sample handling. PMID- 2208697 TI - Examples of enhanced laboratory workflow through the application of robotics. PMID- 2208698 TI - A noninstrumented quantitative test system and its application for determining cholesterol concentration in whole blood. AB - A novel noninstrumented technology has been developed for quantifying analytes of clinical interest in biological fluids. Application of this technology is exemplified by the development of a quantitative cholesterol test with performance equivalent to state-of-the-art instrumented methods. The assay chemistry combines two separate processes located in different areas of a test strip: enzymatic action on serum cholesterol to produce hydrogen peroxide (5 x 10 mm enzyme reagent pad) and quantification of the hydrogen peroxide (5 x 70 mm measurement region). Color bands are formed in the measurement area through the use of a redox-coupled indicator system. The height of the color band on the strip is directly proportional to the sample cholesterol concentration. A one step cassette contains all components necessary to run the test and includes blood filtration and automatic sample measurement, so that unmeasured finger stick whole-blood specimens can be analyzed by the non-technically trained user. The test is complete in less than 15 min, is read visually like a thermometer, and gives results that are in excellent correlation with established instrumented methods. PMID- 2208700 TI - The pursuit of quality in clinical laboratory analyses. PMID- 2208699 TI - The Ciba Corning ACS:180 benchtop immunoassay analyzer. AB - We describe a new clinical laboratory instrument, the ACS:180, used to automate heterogeneous immunoassay testing. The ACS:180 automates immunoassays in which paramagnetic particles are the solid phase and changes in chemiluminescence are measured. The system can accommodate both competitive and sandwich-type assay configurations. The microprocessor-based instrument fully automates each step of the assay, including sample and reagent addition, separation and wash of paramagnetic particles, and generation and acquisition of the chemiluminescent signal. The instrument has the flexibility to operate in random-access or batch mode. The time from application of sample to first result is less than 15 min; throughput is as much as 180 tests per hour. PMID- 2208701 TI - Triglyceride measurements: a review of methods and interferences. AB - The National Cholesterol Education Program has emphasized the need to identify individuals at risk for coronary artery disease (CAD). Because increased triglycerides may be a risk factor for CAD and because triglycerides are used to estimate concentrations of low-density lipoprotein (LDL) cholesterol, which has definitely been shown to be a risk factor for CAD, it is important that reliable results be obtained. Many methods are available for measuring triglyceride concentrations in serum or plasma, but there is no definitive method that confirms the reliability of any of these procedures. Accuracy and precision guidelines are extremely difficult to determine, owing to broad biological variability both within and among individuals. Here, we review the major triglyceride quantification methods in the literature, some of the potential interference problems, and the limitations regarding standardization that should be addressed when establishing such guidelines. PMID- 2208702 TI - Measurement of serum bone gla-protein (BGP) in humans with an ovine BGP-based radioimmunoassay. AB - Most RIAs of serum bone gla-protein (BGP; also called osteocalcin) used for clinical investigation are based on bovine BGP for standard, tracer, and immunogen because of the homology between bovine and human BGP. However, ovine BGP differs from human BGP by only five amino acids, being identical from residues 11 to 49, as compared with homology at residues 20-49 between bovine and human BGP. In screening various anti-ovine BGP polyclonal anti-sera we selected one (R310) that exhibits apparently complete cross-reactivity with human BGP, as assessed by dilutions of 13 human sera from normal subjects and from patients with bone disease. This RIA gave a 42% binding at a 10,000-fold final dilution, with intra- and interassay variations less than 7% and 11%, respectively. Gel filtration chromatography of human serum showed a single immunoreactive peak. Synthetic fragments of human BGP 1-10, 7-19, 25-37, and 37-49 were not recognized by R310, suggesting that either a mid-molecule region or a conformational epitope was its target. Using this RIA, we determined that serum BGP increased with age in women (P less than 0.02), by a mean of 90% from ages 30 to 70 years. Serum BGP was also increased in patients with primary hyperparathyroidism, renal osteodystrophy, and Paget's disease. In contrast with the "normal" concentrations of BGP detected with an anti-bovine BGP antiserum (R102), serum BGP was increased in patients with postmenopausal osteoporosis as measured with the R310 ovine assay, suggesting a greater sensitivity for the latter assay. PMID- 2208703 TI - Setting analytical goals for random analytical error in specific clinical monitoring situations. AB - Strategies abound for the setting of analytical goals in clinical chemistry. Many, especially those more recently proposed for particular clinical situations, are concerned with tests used in diagnosis. We suggest a general theory for the setting of goals in situations that specifically involve the monitoring of individuals. Goals are calculated from the formula CVA less than [(delta c 2/2Z2) CVB2]1/2, where CVA is the analytical imprecision (as coefficient of variation, CV); delta c is the percentage change in serial results that is considered clinically significant; Z is the Z-statistic, which depends only on the probability selected for statistical significance; and CVB is the average inherent within-subject biological variation (as CV). Examples given show applications in hematology and in monitoring diabetes mellitus, chronic renal failure, and hepatitis. The derived goals are for total random analytical error (imprecision and intermittent systematic variation), and provide objective criteria that should be achieved in practice. The effect of analytical variability on both variability in test results and the probability that a stated change can be considered significant should be calculated whether or not the goals are attained. PMID- 2208704 TI - Effect of reticulocytosis on lactate dehydrogenase isoenzyme distribution in serum: in vivo and in vitro studies. AB - We investigated the effect of reticulocytosis on the lactate dehydrogenase (LD; EC 1.1.1.27) isoenzyme LD1/LD2 ratio in patients with and without evidence of hemolytic disease. Analysis of sera from patients with reticulocytosis and in vivo hemolysis showed a mean LD1/LD2 ratio of 0.92 compared with a ratio of 0.69 in patients with in vivo hemolysis and normal reticulocyte counts. Determination of LD isoenzymes in erythrocyte lysate revealed significantly increased LD1/LD2 ratios for patients with marked reticulocytosis compared with those for patients with normal-to-minimal increases in reticulocytes. Finally, separation of mature erythrocytes and reticulocytes by flow cytometry revealed marked differences in the LD1/LD2 isoenzyme distribution between these two cell types. The ability of hemolysis to cause a "flipped" LD1/LD2 ratio is dependent on the proportion of the hemolyzed cells that are reticulocytes. PMID- 2208706 TI - Electrode measurement of glucose and urea in undiluted samples. AB - The development of ion-selective electrodes (ISEs) for electrolyte measurements necessitates a re-evaluation of the biological and clinical interpretation of a result. In pathological situations (e.g., hyperlipidemia and hyperproteinemia) direct potentiometry is the method of choice for ion measurements in blood. However, the "plasma water effect" exists also in normal samples, requiring new reference values for physiological ranges. A compromise between medical and instrumentation workers retained the old reference values (flame photometry for Na+ and K+) by introducing correction factors into the ISE instruments, so that the results for direct ISE and flame photometry are the same for "normal" samples. Analyses of "abnormal" samples will reveal biases between the two methods. Now, a new generation of electrodes for assaying additional metabolites reopens the issue. Although classical methods measure a quantity of substance in a predetermined volume of sample, the majority of the substance is usually in the aqueous phase, and the volumes occupied by lipid and protein are not taken into consideration. In evaluating the NOVA 12 instrument (NOVA Biomedical), using electrodes for direct measurement in serum or plasma of Na, K, Cl, total CO2, urea, and glucose, we have demonstrated the inadequacy of classical measurements of urea and glucose, especially in pathological situations characterized by a large variation in the plasma water fraction. PMID- 2208705 TI - Preventing ascorbate interference in ion-chromatographic determinations of urinary oxalate: four methods compared. AB - In an attempt to decrease ascorbate interference on the ion-chromatographic determination of urinary oxalate, we compared the effectiveness of four different methods for ascorbate elimination by analyzing a representative urine pool supplemented with successive ascorbate additions. Two of the methods--treatment with ferric ions or boric acid--have been described elsewhere; treatments with nitrites or ascorbate oxidase (EC 1.10.3.3) are investigated here as possible alternatives. Consideration of the main features, advantages, and drawbacks of the four procedures leads us to conclude that boric acid dilution is a good routine method and that pre-incubation with ascorbate oxidase reliably prevents ascorbate interference in assays of urinary oxalate. PMID- 2208707 TI - Effect of blood collection and processing on radioimmunoassay results for apolipoprotein B in plasma. AB - We studied the effects of different blood collection and processing procedures on quantification of apolipoprotein (apo) B by radioimmunoassay. High-density lipoprotein subfractions HDL3 and HDL2 and isolated apoA-I did not cross-react in the assay. Analytical recovery of apoB at different doses of very-low- and low density lipoproteins were complete. Inter- and intra-assay coefficients of variation (CVs) averaged 7.4% and 6.0%, respectively. Blood from 20 subjects was collected into tubes containing EDTA alone or EDTA with antiproteolytic and antioxidant agents; one half of each plasma was separated immediately, half after 3 h at 4 degrees C. Regardless of the addition of protective agents or the time difference in separating plasma from other blood elements, freezing plasma at -70 degrees C decreased apoB content a similar amount, an average of 6.8%. This loss of apoB immunoreactivity was not related to apoB content in fresh plasma. Analysis of variance showed no differential effect on apoB content by the various additions to whole blood or plasma. No additional apoB content was lost in once frozen aliquots of three human plasma pools during storage at -70 degrees C for up to 18 months. We conclude that concentrations of apoB in human plasma can be measured reliably after long-term storage, although the absolute value may decrease slightly as a result of freezing. PMID- 2208708 TI - Direct solid-phase time-resolved fluoroimmunoassay of 17 alpha hydroxyprogesterone in serum and dried blood spots on filter paper. AB - We describe a direct, solid-phase time-resolved fluoroimmunoassay (TRFIA) for measuring 17 alpha-hydroxyprogesterone (17OHP) in serum and blood spots on filter paper. We used 17OHP-3-carboxymethyloxime (17OHP3CMO) coupled to polylysine as the label, which enabled incorporation of up to 34 atoms of europium per molecule of 17OHP, for a very high specific activity. The assay is based on competition between labeled 17OHP3CMO and 17OHP in blood specimens for polyclonal rabbit anti 17OHP antibodies. The antibody-label complex is separated by binding to anti rabbit antibodies coated onto microtiter strips. The assay buffer contains danazol to displace 17OHP from steroid-binding proteins in serum. For serum samples, the assay is accomplished in 1 h of incubation at room temperature. The blood spot assay with filter paper discs involves incubation overnight at 4 degrees C. Results for both types of specimens from the same subjects correlated well. The lowest measurable concentrations of 17OHP (nmol/L) were 0.10 (3 SD) and 0.75 (3 SD) for serum and dried blood on filter paper, respectively. Intra- and interassay CVs were about 5-15% for both types of samples. PMID- 2208709 TI - Use of serum cholesterol/triglyceride ratio to discern for which individuals the Friedewald formula can be used confidently. AB - The values of low-density lipoprotein cholesterol obtained according to the Friedewald formula (Clin Chem 1972; 18:499-502), or by the De Long transformation (J Am Med Assoc 1986;256:2372-7), were compared with the values obtained when the individual cholesterol/triglyceride ratio of very-low-density lipoprotein was used for estimating the contribution of this lipoprotein to the total cholesterol. We found that these formulas gave the greatest errors for individuals with a low serum cholesterol/triglyceride ratio. We propose criteria for deciding when the numerically calculated value of low-density cholesterol is appropriate, and when it is not. PMID- 2208710 TI - Quantitative nephelometric assay for determining myoglobin evaluated. AB - A recently introduced automated nephelometric immunoassay involving shell/core particles for determination of myoglobin (Behringwerke) was evaluated with the BNA Nephelometer. Method precision was good: the intra-assay CV varied between 1.5% and 6.1%; with daily calibration, the interassay CV ranged between 1.5% and 7.5%. For usual sample dilutions, the assay response varied linearly with myoglobin concentrations up to 23.1 nmol/L. After automatic dilution by the instrument, concentrations up to 2310 nmol/L could be measured without high-dose "hook" effect. Further manual dilution allowed measurement of myoglobin concentrations up to 26,000 nmol/L. Calibration was stable for at least seven days. We detected no significant interferences from hemoglobin, haptoglobin, bilirubin, iodine-containing contrast media, and rheumatoid factors. Treating lipemic samples with Lipoclean (Behringwerke) decreased test results. Simultaneously drawn serum and plasma samples from the same subject showed no consistent differences in myoglobin concentrations. The mean reference myoglobin concentration was 1.380 (SD 0.82) nmol/L for men and 0.878 (SD 0.45) nmol/L for women. In patients with renal insufficiency, serum creatinine values were moderately related to serum myoglobin values (r = 0.465). Although a commercial radioimmunoassay (Byk-Sangtec) and the nephelometric assay intercorrelated well (r = 0.929), values obtained by nephelometry were significantly lower (P less than 0.05). By both assays, results for heart and skeletal muscle tissue extracts showed no correlation, a finding that suggests the existence of multiple forms of myoglobin in human tissues. We conclude that immunonephelometry is a rapid, practical, and reliable method for measuring myoglobin in serum. PMID- 2208711 TI - Assay of creatine kinase isoenzyme MB in serum with time-resolved immunofluorometry. AB - We describe the first time-resolved immunofluorometric assay for creatine kinase (EC 2.7.3.2) isoenzyme MB (CK-MB) in serum. The assay is based on the formation of the complex: solid-phase anti-CK-MB-CK-MB-biotinylated anti-CK-BB-streptavidin BCPDA-Eu3+, where anti-CK-MB and anti-CK-BB are monoclonal antibodies against the CK isoenzymes MB and BB, respectively, and BCPDA is the europium chelator 4,7 bis(chlorosulfophenyl)-1,10-phenanthroline-2,9-dicarboxylic acid. The solid-phase complex is fluorescent and is measured on the dry solid-phase (microtiter well) in a specially designed time-resolved fluorometer that uses laser excitation. The assay requires 25 microL of serum and is not affected by the presence of either CK-MM (up to 5000 micrograms/L) or CK-BB (up to 1000 micrograms/L) in the sample. Precision and accuracy indices for the assay were satisfactory. PMID- 2208712 TI - Three highly sensitive "bedside" serum and urine tests for pregnancy compared. AB - We examined three enzyme-linked immunosorbent assay (ELISA) kits for human choriogonadotropin (hCG) (pregnancy tests) for use with urine and serum samples: the Tandem Icon II hCG Urine and Tandem Icon II hCG Serum, the NovoClone Target hCG Test, and the Abbott TestPacks hCG-urine and hCG-serum. Paired comparison of the results from each kit indicated that the NovoClone Target assay showed significantly lower diagnostic sensitivity (P less than 0.05) than did the Tandem Icon II or Abbott TestPack, both for urine and for serum samples. None of the products demonstrated any significant difference (P greater than 0.05) in diagnostic specificity, but the NovoClone Target kit showed several serious false negative results with both urine and serum. Paired testing of urine kits vs serum kits also showed no significant differences (P greater than 0.05) in diagnostic sensitivity or specificity. We found the Abbott kits to be the most convenient to use and to read. PMID- 2208713 TI - Measuring arginine vasopressin in children and babies. PMID- 2208715 TI - Radioimmunoassay for pepsinogen C. PMID- 2208714 TI - Discordant results for lutropin among immunoassays in two cases of male hypogonadism. PMID- 2208716 TI - Simplified fluorometric determination of salicylate in plasma. PMID- 2208717 TI - Screening for paucialbuminuria with frozen urine samples. PMID- 2208718 TI - Effects of four days of regular, moderate consumption of ethanol on high-density lipoprotein cholesterol concentrations in plasma. PMID- 2208719 TI - Interpretation of a 2-h change in the serum concentration of creatine kinase 2. PMID- 2208720 TI - Use of the likelihood ratio for calculating predictive value of a CK-MB measurement for perioperative myocardial infarction: three methods compared. PMID- 2208721 TI - Reference interval for transthyretin in children ages six to 60 months. PMID- 2208722 TI - Medium-chain acyl-CoA dehydrogenase deficiency: a useful diagnosis five years after death. AB - We report a family in whom a fatal case of medium-chain acyl-CoA dehydrogenase (MCAD; EC 1.3.99.3) deficiency was diagnosed by enzymatic analysis of heart tissue that had been stored for five years. Three healthy siblings underwent subsequent investigation with the 3-phenylpropionic acid loading test. All siblings had been asymptomatic; however, one (age 2.5 years) excreted large amounts of 3-phenylpropionylglycine in response to the load and exhibited an organic aciduria consistent with the diagnosis of MCAD deficiency. The other two siblings did not demonstrate 3-phenylpropionylglycinuria after the loading test. This case underlines the importance of considering family history and using appropriate diagnostic tests in the recognition of hereditary metabolic disorders. PMID- 2208723 TI - Molar absorptivities of bilirubin (NIST SRM 916a) and its neutral and alkaline azopigments. AB - Three laboratories in the U.S. and two in the Netherlands determined molar absorptivities (epsilon) of Standard Reference Material (SRM) 916a Bilirubin from the National Institute of Standards and Technology. In caffeine reagent the average epsilon values were 50,060 and 48, 980 L.mol-1.cm-1 at 432 and 457 nm, respectively. The epsilon value of the blue azopigment, obtained with the Reference Method for total serum bilirubin, was 76,490 L.mol-1.cm-1 at 598 nm. When the addition of alkaline tartrate was omitted, the molar absorptivity of the red azopigment was 56,600 L.mol-1.cm-1 at 530 nm. PMID- 2208724 TI - Abbott spectrum design flaw allows the mismatching of patients' results. PMID- 2208725 TI - More on detection of cystic fibrosis by polymerase chain reaction. PMID- 2208726 TI - Modify the oral glucose tolerance test? PMID- 2208727 TI - Effect of temperature on glucose results obtained with the Reflolux II. PMID- 2208728 TI - Units and nomenclature for assays of estradiol and progesterone receptors. PMID- 2208729 TI - 25-year cumulative index. 1964-1988. PMID- 2208730 TI - International Federation of Clinical Chemistry. Scientific Division, Committee on Enzymes. IFCC methods for the measurement of catalytic concentration of enzymes. Part 7. IFCC method for creatine kinase (ATP: creatine N-phosphotransferase, EC 2.7.3.2). IFCC recommendations. PMID- 2208731 TI - International Federation of Clinical Chemistry (IFCC). Scientific Division. Committee on pH, Blood Gases and Electrolytes. Guidelines for transcutaneous pO2 and pCO2 measurement. AB - This document provides guidelines in the terminology, methodology, and in the interpretation of data obtained from the use of skin (transcutaneous) pO2 and pCO2 electrodes. The transcutaneous technique has found special application in newborn infants. The causes of analytical bias with respect to arterial blood gas values and imprecision obtained with transcutaneous pO2 and pCO2 electrodes are reviewed. Electrode temperatures above 44 degrees C should not be used routinely, and at a measuring temperature of 44 degrees C, the measuring site should be changed at least every 4 h to avoid skin burning. PMID- 2208732 TI - International Federation of Clinical Chemistry (IFCC). Education Division, Expert Panel on Quantities and Units. A protocol for the conversion of clinical laboratory data. PMID- 2208733 TI - The biology of transferrin. AB - The chemistry and molecular biology of transferrin is discussed. The discussion covers the genetic control of transferrin synthesis, its intracellular synthesis, intra- and extracellular transport, and its interaction with transferrin receptors. The role of transferrin in iron metabolism is evaluated, both with regard to iron uptake by transferrin as to iron uptake from transferrin by different cells. The knowledge on the biochemical mechanisms involved in iron uptake is presented, with special reference to the triple role of the acidification of endocytotic vesicles. Apart from its traditional role in iron metabolism, transferrin acts as a growth factor. A distinction of two groups of growth-stimulating properties of transferrin has been made. As an early effect, membranous and intracellular changes are initiated, possibly based on electrochemical effects on the cell. The late effects seem to relate to its role in iron transport. Interestingly, the early growth stimulating effects can be segregated from the former function of transferrin and strictly speaking neither depend on iron nor on the transferrin molecule itself. Also the trophic effect of transferrin on several cell types has been described. Hypotheses concerning the biochemical basis of this effect are presented and within this context a new hypothesis on the differential occupation of iron binding sites of serum transferrin is forwarded. Examples of the applicability of present understanding of the biology of transferrin in clinical settings are presented. PMID- 2208734 TI - Seed oils containing fatty acids with conjugated double bonds as substrates for lipase assay. PMID- 2208735 TI - Glucose interferes with inulin determination by the resorcinol method: overestimation of glomerular filtration rate in diabetic patients. PMID- 2208736 TI - Plasma fibronectin in patients affected by psoriasis: relation with the extension of skin involvement and complications. PMID- 2208737 TI - Improved HPLC method for the determination of cephalosporins in human plasma and a new solid-phase extraction procedure for cefazolin and ceftizoxime. PMID- 2208738 TI - Incidence and properties of aspartate aminotransferase-immunoglobulin complexes in patients with a high serum aspartate to alanine aminotransferase ratio. AB - Sera of 260 patients with high serum aspartate aminotransferase (L-aspartate: 2 oxoglutarate aminotransferase, EC 2.6.1.1; AST)/alanine aminotransferase (L alanine: 2-oxoglutarate aminotransferase, EC 2.6.1.2; ALT) ratio (greater than 2.0) and high serum AST (greater than 45 IU/1) were selected and tested for the presence of immunoglobulin complexed-AST, by using immunoprecipitation reaction and counterimmunoelectrophoresis. The macromolecular AST was confirmed by size exclusion high-performance liquid chromatography (HPLC). 34 patients out of 260 were found to have AST-immunoglobulin complexes (13.1%). The classes of AST linked immunoglobulins were identified to be alpha in 28 cases (82.4%, P less than 0.01), mixed type of alpha and gamma in 5 cases (14.7%) gamma in one case (2.9%). Positive frequency was the highest in liver malignancies, either primary (9/26, 34.6%) or metastatic (7/17, 42.2%), followed by other malignancies (6/55, 10.9%) and chronic liver diseases (4/22, 18.2%). Thus, it can be strongly suggested that the immunoglobulin A complexed-AST is frequently found in association with liver malignancies. PMID- 2208740 TI - Liquid chromatographic studies of vitamin B6 metabolism in man. AB - The effects of increased intake of pyridoxine hydrochloride on plasma vitamin B6 metabolism within therapeutic limits (up to 800 mg/day) were investigated. Maximum plasma concentrations of pyridoxal phosphate were attained at relatively low intakes of pyridoxine hydrochloride. Two metabolism thought to be unidentified forms of vitamin B6 were present in subjects taking more than 200 mg of pyridoxine hydrochloride per day as have recently been described. We investigated the possibility that these were isomeric forms of vitamin B6. However, 'Peak 2' metabolite was shown to be probably 4-pyridoxolactone. The metabolism of isopyridoxal has not previously been investigated in man. We demonstrated that it is an active vitamer of the B6 complex in humans. The main fluorescent metabolite of isopyridoxal present in plasma and urine had a similar retention time to 'Peak 1' metabolite. Isopyridoxal was incapable of being directly phosphorylated in rat liver extract and it is therefore unlikely that peak 1 is isopyridoxal phosphate. Its nature remains unknown. PMID- 2208739 TI - A compensatory mechanism improving red cell membrane fluidity in hemodialysed patients. AB - A fluorescence polarization technique with 1,6-diphenyl 1,3,5-hexatriene as a fluorescent probe was used to determine the fluidity of red cell membranes from hemodialysed patients before and after dialysis. After dialysis, there was a decrease in fluidity and activation energy values revealed a significantly changed distribution. The membrane lipid composition showed a significant increase in cholesterol after dialysis (p less than 0.001) and a significant reduction in saturated fatty acids (p less than 0.01) with an increase in unsaturated fatty acids (p less than 0.05). A compensatory mechanism could be suggested involving a reduction of saturated fatty acids in response to the increase in the cholesterol/phospholipid ratio. This could lead to an optimization of membrane fluidity. PMID- 2208741 TI - A method for the rapid detection of urinary glycopeptides in alpha-N acetylgalactosaminidase deficiency and other lysosomal storage diseases. AB - A new method is described for the detection of abnormal urinary oligosaccharide and glycopeptide excretion by thin layer chromatography and differential visualization of oligosaccharides and glycopeptides. This method permits rapid screening and identification of disorders characterized by oligosacchariduria and glycopeptiduria including alpha-N-acetylgalactosaminidase deficiency, angiokeratoma corporis diffusum with glycopeptiduria, aspartylglucosaminuria, galactosialidosis, fucosidosis, GM1 gangliosidosis and sialidoses 1 and 2. Of note, the characterization of the glycopeptide excretion profiles in patients with alpha-N-acetylgalactosaminidase deficiency and angiokeratoma corporis diffusum with glycopeptiduria revealed essentially identical patterns, indicating the metabolic relatedness of these two phenotypically distinct conditions. Use of this improved thin layer chromatographic method should enhance routine screening of patients for lysosomal storage diseases as well as permit the identification of new disorders resulting from defective oligosaccharide and/or glycoprotein metabolism. PMID- 2208743 TI - Predictors of blood pressure and hypertension in Tecumseh, Michigan. AB - Correlates of present blood pressure status are analyzed in 576 subjects (271 males, average age 32 years) in Tecumseh, Michigan. In addition to the current values, anthropometric and blood pressure data are available when the subjects were, on average, 6.9 and 22.2 years of age. Data on 351 fathers and 368 mothers when they were, on average, 32 years old are also available. Moderate, but significant correlations were found between present and past blood pressure and between past weight or skinfold thickness and the present blood pressure. These correlations were much weaker for childhood values than for values at age 22. When multiple regression techniques were used with blood pressure values at age 22 and parental values as independent variables, 40% of the present systolic blood pressure variance could be explained. Prediction of present hypertension status (blood pressure greater than 140 and/or 90 mm Hg) was evaluated by discriminant analysis. Three variables (weight at age 22, systolic blood pressure at age 22, and father's diastolic blood pressure) entered the model and accurately predicted the present blood pressure classification in 89% of the sample. When current blood pressure status was assessed with respect to previous blood pressure classification (upper 20%), family background, and overweight, a gradient of risk for hypertension was found. On the low end of risk was high childhood pressure (risk 19.1% versus 12.1% in the overall population). The highest risk occurred for those with high pressure and overweight at 22 years who also had a family background of high blood pressure (44% versus 12.1%). The prediction of hypertension from young adulthood to the early fourth decade of life is feasible and permits delineation of populations targeted for primary prevention. PMID- 2208742 TI - Heterogeneity of urinary albumin from diabetic patients. AB - A fundamental cause of diabetic microalbuminuria, heterogeneity of normal and diabetic urinary albumin was shown by affinity chromatography on Cibacron Blue F3GA. By changing the properties of interaction with the matrix, the protein was separated into six fractions. Samples of urinary albumin from proteinuria patients showed the same elution profiles as those of serum albumin, whereas those from controls or normoalbuminuria diabetic patients exhibited different elution patterns. The relative percentage of the resin unbound fraction of urinary albumin was ten or more times higher than that of serum albumin, and the ratio decreased with increasing albumin excretion into urine. More than 6 mol fatty acid/mol albumin combined with the unbound fraction. It is suggested that microalbumin excretion into urine is the result of excessive unesterified fatty acid binding to the protein. PMID- 2208744 TI - Proceedings of the joint WHO/ISH symposium on the Prevention of Hypertension and Cardiovascular Disease. Gothenburg, Sweden, September 4-6, 1989. PMID- 2208745 TI - Effects of non-pharmacologic therapy. AB - Whereas there is no doubt that non-drug treatment of hypertension, and modifications in life-style to prevent an age-associated rise in arterial pressure are attractive concepts, opinions vary as to what advice should be offered to hypertensive patients and to populations at large. No modification in diet or life style has been demonstrated to reduce the complications of hypertension. Review of recent reports suggests that moderate exercise, weight reduction in the obese, and moderation of alcohol intake are usually effective in reducing arterial pressure and are unaccompanied by adverse effects. On the contrary, restriction of dietary sodium, or supplementation with potassium, calcium or magnesium have little or variable antihypertensive effects, are not readily accepted by a high percentage of the population, and could have adverse consequences. Other dietary modifications may reduce blood pressure, but additional research is needed to define the relevant component in the diet. PMID- 2208746 TI - The Canadian consensus report on non-pharmacological approaches to the management of high blood pressure. AB - The Canadian Consensus Conference on Non-Pharmacological Approaches to the Management of High Blood Pressure reviewed in March, 1989 on its meeting in Halifax, Nova Scotia, data concerning the efficacy of eight interventional strategies used for controlling hypertension. These strategies were as follows: alcohol restriction, weight reduction, physical exercise, reduction of salt intake, relaxation/stress management, increase of potassium and calcium intake and combination of pharmacological and non-pharmacological management. The Panel of the Consensus Conference recommended as efficacious the following interventions: alcohol restriction for less than two standard drinks per day, reduction of excessive body weight, and reduction of salt intake. There is sufficient scientific evidence for recommending potassium rich diet for normotensives and hypertensive persons. The Panel also concluded that a combination of pharmacological and non-pharmacological management is an efficacious measure. The Panel at this point of time could not issue recommendations as to the value of relaxation/stress management, physical exercise and calcium intake. PMID- 2208747 TI - Hypertension and ageing. AB - Hypertension is a common problem in the elderly with a prevalence approaching or exceeding 50%. The risk of cardiovascular disease and death is increased in elderly hypertensives aged 60-74 years, whereas this increased risk seems to be diminished or even nonexistent in those aged 75 and above. Hypotensive drug treatment has been shown to be beneficial for the younger elderly patients, but whether or not this is also true for the older elderly hypertensives is less clear. Isolated systolic hypertension increases the cardiovascular risk, but we lack data on the efficacy of treatment in this group. PMID- 2208748 TI - Lipid effects of antihypertensive drugs. AB - Despite the well-established correlation between coronary heart disease (CHD) and hypertension, conventional antihypertensive therapy with diuretics and beta adrenergic blockers has failed to provide protection against CHD. A possible explanation for this failure is the unfavourable effect such drugs have on lipid metabolism. To compare the lipid profiles of commonly used antihypertensive drugs, a survey was made of selected studies from the literature. Diuretics and selective and nonselective beta-blockers were found to have adverse effects on blood lipids. Beta-blockers with intrinsic sympathomimetic activity, labetalol, methyldopa, calcium channel blockers and ACE-inhibitors are lipid neutral, whereas alpha-adrenergic blockers seemed to have a favourable effect on lipid metabolism. Controlled clinical trials with drugs that have no adverse effects on lipid metabolism are needed to establish the long-term clinical importance of such agents. PMID- 2208749 TI - Obesity, hypertension and stroke. AB - Central fat distribution may be more closely associated with stroke risk than relative weight or body mass index, although both are associated with hypertension. Some of this association may reflect the fact that central obesity reflects adult weight gain, which may be more relevant to stroke risk than weight in old age. Three attributes associated with central obesity, hypertension and stroke risk deserve further exploration as a possible explanatory variables for the central obesity-stroke risk association. They are cigarette smoking, heavy alcohol intake and diabetes. Prevention of smoking and excess alcohol intake would be consistent with general public health guidelines and might be more relevant to stroke prevention than caloric reduction and management of general overweight. PMID- 2208750 TI - Abdominal obesity and risk. PMID- 2208751 TI - Energy restriction or salt restriction in the treatment of overweight hypertension. Which one? A point of view. AB - Body weight reduction in the overweight hypertensive patient was found to reduce blood pressure, irrespective of the daily urinary sodium excretion. Significant blood pressure reductions were achieved while the urine sodium excretion was between 165-185 mEq/day. Salt restriction resulting in a significant decrease of the 24-hour urine sodium from 192-110 mEq/24-hours did not change the blood pressure. Some of the studies indicating a reduction in blood pressure, did not take into account the changes in body weight, while on sodium restriction. Thus sodium restriction in the treatment of hypertension has not been uniformly found to reduce the blood pressure. Although there is much evidence in favour of the involvement of sodium in the regulation of blood pressure, there is no convincing evidence that dietary sodium restriction can be of use as a therapeutic modality in the treatment of hypertension in the overweight hypertensive patient. PMID- 2208752 TI - Insulin and hypertension. AB - Patients with hypertension have been shown to be resistant to insulin-stimulated glucose uptake and hyperinsulinemic when compared to matched control groups with normal blood pressure. In addition, insulin resistance and hyperinsulinemia have been demonstrated in rat models of hypertension-including SHR rats and Sprague Dawley rats fed a fructose-enriched diet. Furthermore, fructose-induced hypertension can be attenuated by experimental interventions which decrease insulin resistance and/or hyperinsulinemia. These observations raise the possibility that insulin resistance and hyperinsulinemia may play a role in blood pressure regulation. Finally, insulin resistance and hyperinsulinemia increase risk of coronary artery decrease in patients with hypertension, both directly, and indirectly by their influence on very low density and high density lipoprotein metabolism. PMID- 2208753 TI - Insulin resistance, energy balance and sympathetic nervous system activity. AB - Insulin resistance and hyperinsulinemia are commonly associated with hypertension in the obese. The nature of this association is obscure. An hypothesis is developed that attributes obesity-related hypertension to sympathetic stimulation. The relationship between insulin and the sympathetic nervous system (SNS) has its origins in the mediation of dietary thermogenesis. Fasting suppresses while carbohydrate and fat feeding stimulate sympathetic activity. Insulin-mediated glucose metabolism within critical central neurons links dietary intake and central sympathetic outflow. The sympathetic nervous system, in turn, contributes to changes in metabolic rate that accompany alterations in dietary intake. It is hypothesized that insulin resistance is a mechanism recruited in the obese to limit further weight gain and stabilize body mass. Insulin-mediated sympathetic stimulation is one mechanism that may restore energy balance in the obese since the obese are not resistant to the stimulatory effect of insulin on the SNS. Sympathetically mediated stimulation of the heart, vasculature and kidney contributes, in genetically predisposed individuals, to the development of hypertension. Viewed in this light, obesity-related hypertension is the unfortunate by-product of an adaptive mechanism (insulin resistance) recruited to restore energy balance in the obese. Possible implications of this formulation are discussed. PMID- 2208754 TI - Epidemiology of hypertension and cardiovascular disease--China experience. AB - Epidemiological studies show higher BP level, lipid level and higher prevalence of coronary atherosclerosis and stenosis, in north than in south China. Urban populations have higher prevalence of HT than rural, high altitude dwellers usually have lower prevalence. Genetic differences start to affect BP from early childhood, children from higher BP parents are found more salt sensitive. Higher Na and Na/K, lower protein and Ca in the north, are important dietary factors in explaining north-south difference. Low prevalence of high altitude dwellers is found to be related with low salt intake, less stress perhaps also hypoxia. CVD Community control program has started since 1969, from 1969-1989, eleven such programs have been established in Beijing covering a total population of 750,000. Encouraging results in reduction of CVD mortality and morbidity rates have been obtained. Primary prevention by restriction of Na and supplementation of calcium has been tried and found to be eligible preventive measures. PMID- 2208755 TI - Synergistic effects of risk factors. AB - Risk factors for coronary heart disease (CHD), stroke, congestive heart failure and total mortality were analysed in two random population samples of men in Gothenburg, Sweden, aged 50 and 47-55 years, respectively, at entry. A series of potential risk factors for the above mentioned end-points have been analysed in univariate and multivariate logistic analyses. Population attributable risks were also calculated. Significant risk factors in multivariate analyses are summarized. For CHD they were: family history of CHD, hypercholesterolemia, hypertension, tobacco smoking, psychologic stress, low social class and diabetes mellitus. In hypertensives, proteinuria was measured and found to be significant also. Stroke risk factors were: family history of stroke, blood pressure, smoking, high waist/hip ratio, high plasma fibrinogen, psychologic stress, proteinuria, atria fibrillation and transitory ischemic attacks. Hypertension, smoking, high waist/hip ratio and psychologic stress were risk factors for congestive heart failure. PMID- 2208756 TI - Genetics of hypertension: what we know and don't know. AB - Human arterial hypertension is likely a multifactorial trait resulting from multiple measurable monogenes, blended polygenes, shared family environment, and individual environment. Familial aggregation of hypertension and familial correlation of blood pressure appears to be more due to genes than to shared family environment. Total genetic heritability of 80% with some recessive major gene effects have been found for several traits associated with hypertension including urinary kallikrein excretion, intraerythrocytic sodium, and sodium lithium countertransport. Other interesting factors regarding hypertension genetics include: non-modulation of the renin angiotensin system, intralymphocytic sodium, ionized calcium, and several genetic markers such as haptoglobin, HLA, and MNS blood type. Probably the most clinically useful information regarding the genetics of hypertension is evolving in several studies reporting a strong association of hypertension with dyslipidemia, diabetes, and obesity. PMID- 2208757 TI - Endothelial control of vascular tone and growth. AB - Endothelial cells play an important regulatory role in the circulation as a physical barrier and as a source of a variety of regulatory substances. Endothelium-derived nitric oxide and prostacyclin are released in response to physical stimuli, hormones and platelet-derived substances and induce vascular relaxation and inhibition of platelet function. Certain substances can evoke a hyperpolarization of smooth muscle cells. In addition, endothelial cells can release several contracting factors (i.e. endothelin, thromboxane A2, angiotensin II, superoxide and unidentified endothelium-derived contracting factors), at least under certain conditions. Endothelial cells are also a source of growth inhibitors and promoters, such as heparin and heparin sulphates, platelet-derived growth factor and thrombospondin. Several vasoactive substances produced by the endothelium, such as nitric oxide, endothelin and angiotensin II may also play a role in the regulation of vascular growth. Thus, the endothelial layer can regulate vascular tone and growth. A dysfunction of these endothelium-dependent regulatory systems may play a role in cardiovascular diseases, such as hypertension and atherosclerosis. PMID- 2208758 TI - Cardiovascular effects of smoking. AB - Coronary heart disease (CHD) increases with smoking and this factor interacts with hypercholesterolemia and hypertension in raising the incidence of this condition in a greater than linear fashion. This can be explained by the adverse effect of smoking on plasma fibrogen, platelet turnover and lipid profile. It may also be accounted for, however, by the acute bradycardia, increase in blood pressure and generalized vasoconstriction accompanying smoking, due to a nicotine dependent activation of the sympathetic nervous system. These effects (which in heavy smokers can raise blood pressure permanently) are only partly offset by beta-blockers and can only be abolished by opposing the cardiac and vascular sympathetic influences by alpha and beta-blockade combined. PMID- 2208759 TI - Cardiovascular risk factors: multiple interventions in man. AB - Cardiovascular disease, especially coronary heart disease, is multifactoral. Therefore, it is reasonable to use multiple interventions to try to obtain the greatest reduction in risk. This has been attempted in several controlled clinical trials and in two community educational trials. The results have been variable, showing either benefit or a favorable trend with no statistically significance change. Although the benefit of multiple intervention has not been conclusively demonstrated, there has been a downward trend in cardiovascular mortality in many countries which parallels a downward trend in the level of cardiovascular risk, supporting the concept of benefit from multiple intervention. PMID- 2208760 TI - Experimental intervention of hypertension and cardiovascular diseases. AB - Experimental prevention of hypertension and related cardiovascular diseases has been studied in rat models for hypertension and stroke and not only salt reduction but also increased intakes of potassium, calcium, magnesium, protein, some amino acids and fatty acids and dietary fibers have been proven to be effective and indicated the importance of nonpharmacological dietary prevention of cardiovascular diseases. These experimental findings contribute to dietary risk factor analyses and the prevention of hypertension and its complications in man, as demonstrated by a cross-sectional epidemiological study on cardiovascular diseases and alimentary comparison (WHO-CARDIAC Study). PMID- 2208761 TI - Morphologic variants in parents of children with malformation syndromes: are they indicators of somatic mosaicism? AB - The ostensibly normal parents of 27 probands with recessive or sporadic multiple malformation syndromes were reexamined. By means of careful investigations and anthropometric measurements in nine of them, morphologic variants were found that were compatible with the syndromes and were also observed in the proband. Although other factors should also be considered, the findings may be explained by germline and somatic mosaicism in the parents. PMID- 2208762 TI - Right-sided microtia and conductive hearing loss with variable expressivity in three generations. AB - Familial cases of microtia and meatal atresia are rare, and both dominant and recessive inheritance have been suggested. We here report a family with right sided external ear malformations and conductive hearing loss in a grandfather, his daughter and granddaughter. The grandfather and the granddaughter both had microtia and meatal atresia, whereas the daughter had a normal outer ear except for a narrow meatus and auricular appendages. The pedigree suggests autosomal dominant inheritance with variable expressivity. PMID- 2208763 TI - Disomic balanced reciprocal translocation. AB - The previously unreported and unique finding of a complete disomy of an apparently balanced reciprocal translocation is described. The parents are second cousins once removed and each parent contributed the same balanced reciprocal translocation chromosome. Although the complete disomy involves balanced translocation chromosomes from unaffected parents, it is possible that a hemizygous state of some genes may be present on each translocation chromosome, which in a disomic homozygous state could result in an abnormal phenotype, as manifested by infantile seizures in this patient. PMID- 2208764 TI - Incontinentia pigmenti: XXY male with a family history. AB - We report on the case of a male who from the start of life displayed vesicular lesions; on the trunk these were clustered and on the limbs they adopted a linear configuration. After biopsy of one such lesion, the histopathological study was compatible with a diagnosis of incontinentia pigmenti (IP). In the following months, hyperkeratotic lesions appeared which later became pigmented. The mother and other female members of the family also showed different degrees of alteration related to the same disease. The karyotype study showed the existence of 47,XXY (Klinefelter syndrome). The exceptional nature of this case is that although it is the third case reported in the literature of a male affected by incontinentia pigmenti with a previous family history, it is the only one combining this characteristic with the presence of a 47,XXY karyotype. PMID- 2208765 TI - The Proteus syndrome: association with nephrogenic diabetes insipidus. AB - In this report we present the first case of Proteus syndrome associated with nephrogenic diabetes insipidus. The case is a 9-month-old girl, with macrodactyly of both feet and left hand, syndactyly of the 3rd and 4th fingers of the left hand, soft tissue masses in the paravertebral and gluteal regions, and a hyperpigmented epidermal nevus with hyperkeratosis on the left half of the body. PMID- 2208766 TI - Congenital tracheal stenosis in Pfeiffer syndrome. AB - We report an infant with Pfeiffer syndrome (acrocephalosyndactyly type V) and a solid cartilaginous trachea lacking rings. This airway abnormality has been reported in a child with Crouzon syndrome but has not been described in Pfeiffer syndrome. PMID- 2208767 TI - Megalocornea, macrocephaly, mental and motor retardation (MMMM). AB - Two patients with macrocephaly, mild mental retardation and megalocornea are reported. Hypotonia, poor coordination and swallowing difficulties were present. One patient was obese and the other had scoliosis. Both had large fleshy ears and long fingers. The spectrum of the mental retardation megalocornea syndrome is not fully defined. These two patients resemble a previously reported case, and although there are distinct differences from patients with familial or sporadic Neuhauser syndrome, these cases may represent clinical variability of that syndrome. PMID- 2208768 TI - Sporadic late onset ornithine transcarbamylase deficiency in a boy with somatic mosaicism for an intragenic deletion. AB - Somatic mosaicism for a deletion in the ornithine transcarbamylase gene is described in a boy with sporadic late onset ornithine transcarbamylase deficiency. These findings are discussed in relation to the clinical picture of the patient and in relation to genetic counseling. PMID- 2208769 TI - Spinal muscular atrophy type I combined with atrial septal defect in three sibs. AB - All three children of an unrelated Norwegian couple were born with spinal muscular atrophy (SMA I) as confirmed by autopsy in two of them. Two of the children died at birth, whereas one lived for 7 weeks on support systems that included artificial ventilation. All three children had large atrial septal defects (ASD). One had valvular aortic stenosis. Another had arrhinencephaly and transient pleural effusion which was evacuated during pregnancy. The findings may reflect concurrence of unrelated disorders caused by genetic or environmental factors, segregation of linked genes, pleiotropism or the existence of a previously unknown disease. PMID- 2208770 TI - Rhizomelic chondrodysplasia punctata and survival beyond one year: a review of the literature and five case reports. AB - Rhizomelic chondrodysplasia punctata (RCDP), a peroxisomal disorder, is considered to be a lethal neonatal autosomal recessive chondrodysplasia. We report five patients, three of whom survived beyond 1 year, and we summarize the findings in 21 patients from a literature review who survived beyond 1 year. In those patients that survive, there is a high association of spasticity, psychomotor retardation, growth failure, seizures, thermoregulatory instability, feeding difficulty, and recurrent otitis media and pneumonia. Three of our five patients had no radiographic evidence of vertebral body clefts, a finding which has previously been considered invariable in RCDP. Three of our patients had distinctive facies that differ from the classic Conradi-Hunermann facies. PMID- 2208771 TI - Immunocytochemistry and cutaneous neoplasia ('something will turn up', Micawber 1863). PMID- 2208772 TI - Chronic erosive vulval disease. AB - The clinical features and differential diagnosis of chronic erosive vulval disease are described. Many cases are examples of erosive lichen planus but a similar picture is sometimes associated with cicatricial pemphigoid, lichen sclerosus et atrophicus, vulval intra-epithelial neoplasia, and vestibulitis, while a few examples still defy categorization. PMID- 2208773 TI - Endemic and atypical Kaposi's sarcoma in Africa--histopathological aspects. AB - Atypical HIV-associated and endemic Kaposi's sarcoma (KS) differ in their clinical presentation and behaviour. To assess the possible histological differences, a detailed review of 32 cases of atypical KS and 170 cases of endemic KS from sub-Saharan Africa was undertaken. Both forms of KS had similar histological appearances, and evolved through a chronological sequence of patch, plaque and nodule. There was an increase in the proportion of early patch and plaque lesions in cutaneous and mucosal atypical KS (54%) compared with endemic KS (23%). However, nodular lesions were still seen in atypical KS, and formed 56% of the total cases. In addition, atypical KS tended to have more small blood vessels and a lesser degree of inflammatory infiltrate. However, within each of the three stages of the disease, it was not possible to distinguish between the HIV- and non-HIV-related forms. PMID- 2208774 TI - Cryotherapy of hand warts--a questionnaire survey of 'consumers'. AB - One-hundred and thirty (82%) of 159 patients who had been treated with cryotherapy for warts on the hands replied to a postal questionnaire. Most patients had wanted treatment for cosmetic reasons, although 35% also wanted treatment because of pain. Only 34% had used a wart paint for more than 6 weeks before referral. The long-term results of cryotherapy were poor, although 83% of patients thought they had been cured in the short-term; only 57% of patients were clear of warts after a median of 19 months' follow-up. Seventy-one per cent had defaulted from follow-up. In some cases this may have been encouraged by the dermatologists, but other reasons were pain, cost and perceived failure of treatment. Nearly 90% tolerated cryotherapy well and for 76% this was the preferred method of treatment. Fifty-nine per cent would have preferred to be treated in their local health centre and 85% would have been willing to be treated by a nurse. The results are discussed and we conclude that cryotherapy should be offered as a treatment for hand warts in most general practices. PMID- 2208775 TI - Blood eosinophilia in atopic dermatitis. AB - Blood eosinophil levels were examined in 200 (100 mild and 100 severe) patients with atopic dermatitis. Eosinophil levels roughly correlated with disease severity. However, the pattern of eosinophilia was not homogeneous. Very high eosinophil counts were common in severe cases of atopic dermatitis who had a personal or family history of respiratory atopy, while normal or moderately elevated eosinophil values were obtained in severe cases of 'pure' atopic dermatitis who had neither personal nor family history of respiratory atopy. It is suggested that disease severity and personal or family history of respiratory atopy are important factors in determining high blood eosinophil levels in atopic dermatitis. PMID- 2208776 TI - Colorimetric quantification of erythema--a comparison of two colorimeters (Lange Micro Color and Minolta Chroma Meter CR-200) with a clinical scoring scheme and laser-Doppler flowmetry. AB - Erythema elicited by the local irritant sodium lauryl sulphate was studied in comparison with unexposed skin. Colour coordinates of the CIE system were recorded using two commercially available colorimeters. With both colorimeters a positive movement of the alpha-axis (toward red, P less than 0.001) and a negative movement on the L-axis (toward dark, P less than 0.01) were registered. Technical and in-vivo experimentation showed the two pieces of equipment to be accurate. However, a simple conversion factor cannot be established. Both pieces of equipment correlated positively with clinical scoring of erythema and with measurement of cutaneous blood flow by laser-Doppler flowmetry. In conclusion, the two colorimeters appeared comparable. Colorimetry by the CIE system, which takes into account the non-linear colour perception of the human eye, was found useful with potential value in both experimental and clinical dermatology. The techniques appeared suitable for routine testing. PMID- 2208777 TI - Occult basal-cell carcinoma within rhinophyma. AB - Rhinophyma, the end stage in the development of rosacea, is characterized by sebaceous hyperplasia, fibrosis, follicular plugging and telangiectasia. Although it is commonly considered a cosmetic problem, it can result in gross distortion of soft tissue and in airway obstruction. Previously, basal-cell carcinoma (BCC) has been reported in association with rhinophyma. We are reporting an additional case in which the patient had been delaying treatment because of the 'cosmetic nature' of this condition. PMID- 2208778 TI - Porphyria cutanea tarda and scleroderma--chance association or related disease: a case report. AB - The concurrence of systemic scleroderma and porphyria cutanea tarda (PCT) seems very rare. Only six cases have been reported to our knowledge. On the other hand, cutaneous sclerodermatous lesions in PCT occur more frequently and can affect 1.8 18% of cases. These observations raise the problem of a possible physiopathological relation between scleroderma and PCT. In fact, Grossman and colleagues have found anti-nuclear antibodies (ANA) in 38% of patients so tested. In the present report, the association of systemic scleroderma and PCT with Sjogren's syndrome and anti-RNP antibodies raises further questions concerning the relationship between PCT and auto-immune diseases. PMID- 2208779 TI - A case of actinic prurigo and solar urticaria. AB - Actinic prurigo and solar urticaria are uncommon chronic idiopathic photodermatoses in the United Kingdom. To our knowledge, their occurrence in the same patient has not hitherto been described. PMID- 2208781 TI - Abstracts from the 16th annual meeting of the Society of Cutaneous Ultrastructural Research. PMID- 2208780 TI - Facial leiomyomas. AB - We present a patient with multiple leiomyomas confined to the left cheek, giving rise to an unusual clinical presentation of this condition. The lesions were cosmetically disfiguring and, because of their exposed location, were particularly painful in the winter months. The treatment of this condition is discussed. PMID- 2208782 TI - Treatment of generalized pruritus in an HIV-positive patient with UVB phototherapy. PMID- 2208783 TI - Erythema nodosum caused by kerion of the scalp. PMID- 2208784 TI - A modified dosage schedule for increased efficiency in PUVA treatment. PMID- 2208785 TI - Amiodarone-induced photosensitivity and basal-cell carcinoma. PMID- 2208786 TI - 8-Methoxypsoralen bath PUVA clears psoriasis after failure of oral PUVA. PMID- 2208787 TI - How does HLA-B27 confer susceptibility to inflammatory arthritis? PMID- 2208788 TI - In vitro production of B cell growth factor and B cell differentiation factor by peripheral blood mononuclear cells and bronchoalveolar lavage T lymphocytes from patients with idiopathic pulmonary fibrosis. AB - The activation of B lymphocytes and formation of immune complexes have been suggested to play an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). To investigate the mechanisms of activation of B lymphocytes, we studied the production of B cell growth factor (BCGF) and B cell differentiation factor (BCDF) in patients with IPF and those with interstitial pneumonia associated with collagen vascular diseases (IP-CVD), in comparison with healthy controls. Culture supernatants of peripheral blood mononuclear cells from patients with IPF induced more IgM and IgA production by B lymphocytes than those from healthy controls, indicating a higher production of BCDF in the patients. Culture supernatants of T lymphocytes obtained from bronchoalveolar lavage fluids (BALF) of patients with IPF induced higher proliferation of B lymphocytes than those from healthy controls, indicating a higher production of BCGF. An increase in production of BCGF and BCDF was not observed in patients with IP-CVD. In the light of these results, it was suggested that there may be an imbalance in T lymphocyte subsets that release lymphokines like BCGF and BCDF in patients with IPF, and that the subsets may differ between blood and BALF. It remains to be elucidated whether the activation of B lymphocytes depending on T lymphocytes determines the development of disease in IPF. PMID- 2208789 TI - In vivo boosting of lung natural killer and lymphokine-activated killer cell activity by interleukin-2: comparison of systemic, intrapleural and inhalation routes. AB - Natural killer (NK) cells are thought to play a role in host defence against malignancy and infection, in immunoregulation and as precursor cells in a generation of lymphokine-activated killer (LAK) cells which can lyse NK-resistant tumour cells. As the lung is a major site for malignancy and infection and as there are large numbers of lymphoid cells including NK cells in the interstitial compartment of the lung, we evaluated the capacity of interleukin-2 (IL-2), a lymphokine capable of augmenting NK activity in vitro, to augment lung NK cell activity in vivo, using different routes of IL-2 administration. We compared both systemic (i.v. and i.p.) and local (intrapleural and inhalation) routes of IL-2 administration (50,000 U/daily for 5 days) using CBA mice, assessing NK and LAK cell activity in the spleen (systemic) and in the lung. The target cells used for these studies were the YAC-1 (NK-sensitive) and P815, NO36 and HA56 (NK resistant, LAK-sensitive) cell lines. Splenic NK activity was increased by 1.4 1.9-fold for i.v./i.p., respectively, compared with controls with both systemic routes of administration, and lung NK activity was increased 3.2-fold and 3.8 fold (i.v./i.p, respectively, P less than 0.05), to levels which were comparable to systemic (splenic) NK activity following the same therapy. Intrapleural IL-2 administration similarly enhanced lung NK activity (3.3-fold) and splenic NK activity (1.3-fold; P less than 0.05 versus controls for both). Surprisingly, inhaled IL-2 suppressed both splenic and lung NK cell activity (84 +/- 8% and 78 +/- 10% suppression, respectively, P less than 0.05). LAK cell activity was also enhanced in the lung by 1.8-8-fold in response to i.v., i.p. and intrapleural IL 2, whereas inhaled IL-2 was ineffective in generating LAK cell activity. These results suggest that the systemic and intrapleural administration of IL-2 effectively boost pulmonary NK and LAK activity whereas inhalation of IL-2 does not. Thus, in clinical situations where boosting of local lung NK or LAK cell activity is desired, these routes of IL-2 administration may be effective. PMID- 2208790 TI - Effect of IgG for intravenous use on Fc receptor-mediated phagocytosis by human monocytes. AB - Polyspecific IgG given intravenously at high doses (IVIG) is used for immunomodulatory therapy in autoimmune diseases such as idiopathic thrombocytopenic purpura and myasthenia gravis. It is assumed that the clinical effect is brought about in part by a modulation of mononuclear phagocyte function, in particular by an inhibition of Fc receptor (FcR) mediated phagocytosis. In the present study, the effect of IVIG on FcR-mediated phagocytosis by monocytes was analysed in vitro. Since monocytes exposed to minute amounts of surface-bound IgG displayed impaired phagocytosis of IgG-coated erythrocytes (EA), the effect of IVIG was studied with mononuclear cells suspended in teflon bags in medium containing 10% autologous serum and IVIG (2-10 mg/ml). Monocytes pre-exposed to IVIG and then washed, displayed impaired ingestion of EA when compared with control cells cultured in 10% autologous serum only. The decrease in phagocytosis was observed with sheep erythrocytes treated with either rabbit IgG or bovine IgG1 and with anti-D-treated human erythrocytes. This suggests that phagocytosis via both FcR type I (FcRI) and type II (FcRII) was decreased. The impairment of phagocytosis was dependent on the presence of intact IgG and was mediated by IVIG from nulliparous donors and from multigravidae to the same extent, suggesting that alloantibodies contained in IVIG have a minor role in modulating FcR-mediated phagocytosis by monocytes. A flow cytometric analysis using anti-FcRI, FcRII and FcRII monoclonal antibodies showed that IVIG treatment upregulated FcRI expression but did not significantly alter the expression of FcRII and FcRIII. PMID- 2208791 TI - NADP+ reduction by human lymphocytes. AB - The hexose monophosphate shunt (HMPS) is known to be responsible for the reduction of NADP+ by lymphocytes. We tried to find other enzymatic systems that might provide the lymphocytes with NADPH. By measuring the absorbance at 340 nm we noted that the addition of NADP+ to a preparation of disrupted lymphocytes resulted in the formation of NADPH at a rate of 4 nmol/10(6) cells per min. This phenomenon could not be changed by negative feedback inhibition of HMPS, and could not be attributed to the low concentration of glucose, glucose-6-phosphate (G-6-P) and isocitrate found in the cell preparation (NADP(+)-dependent isocitrate dehydrogenase in addition to HMPS NADP+ reducing enzymes was found to be present in lymphocytes). Because of the activity of a NADP(+)-dependent lactate dehydrogenase, pyruvate oxidized the NADPH as it was being formed. Here we demonstrate the presence of an unknown NADP+ reducer in lymphocytes which seems to play an additional role to HMPS in NADP+ reduction by lymphocytes. NADP(+)-dependent lactate dehydrogenase may play a role in regulating the NADP+/NADPH ratio. PMID- 2208792 TI - Characterization of two monoclonal antibodies (UCL4D12 and UCL3D3) that discriminate between human mantle zone and marginal zone B cells. AB - Two new monoclonal antibodies (MoAbs), UCL3D3 and UCL4D12 were obtained following immunization with follicular lymphoma (UCL3D3) or low-grade primary B cell gastric lymphoma cells (UCL4D12). In normal splenic white pulp, tonsil and small intestinal Peyer's patches, UCL4D12 recognizes marginal zone B cells and a subpopulation of follicle centre cells, whereas mantle zone B cells are UCL4D12 negative. In contrast, UCL3D3 recognizes mantle zone B cells and follicular dendritic cells, but not marginal zone B cells or follicle centre B cells. Double immunofluorescence studies showed that in the splenic white pulp, these antibodies stain reciprocally. The majority of UCL3D3+ cells are sIgM+ and sIgD+ whereas a higher proportion of UCL4D12+ cells express surface IgM (sIgM) but not surface IgD (sIgD). Less than 10% of splenic B cells express both 3D3 and 4D12 antigens. None of the cell lines tested expressed either antigen. Functional studies showed that both antigens play a role in B cell activation as the MoAbs increase the mitogenic effect of Staphylococcus aureus Cowan I on tonsil B cells. This effect was maximal at 72 h in culture. TPA activation was reduced, and no effect was observed with anti-immunoglobulin (anti mu) or CDw40 (G28.5). UCL3D3 and UCL4D12 did not show any stimulatory effect on their own. Biochemical studies show that both MoAbs recognize proteins of 80-90 kD under reducing conditions. These two MoAbs appear to recognize new B cell surface antigens which may be useful for identifying subpopulations of B cells. PMID- 2208793 TI - Changes in plasma levels of interleukin-2 receptor in relation to disease exacerbations and levels of anti-dsDNA and complement in systemic lupus erythematosus. AB - Interleukin-2 receptor (IL-2R) is expressed and released predominantly by activated T cells. In order to investigate whether disease exacerbations of systemic lupus erythematosus (SLE) are preceded by T cell activation, we prospectively measured levels of IL-2R once a month, from 6 months prior to exacerbations until 1 month afterwards. To assess the temporal relation between T cell activation and B cell activation, we measured, in addition, levels of anti dsDNA, complement C3/C4, and total IgG. During a mean follow-up period of 23 months, 40 exacerbations occurred in 21 out of the 71 participating patients. For the present study one exacerbation per patient was evaluated. During exacerbation levels of IL-2R were increased in 18 out of the 21 cases and correlated with levels of anti-dsDNA (P less than 0.02), C3 (P less than 0.02), and C4 (P less than 0.01), but not with the score of the disease activity index. Levels of IL-2R rose prior to the exacerbation (P less than 0.02) and fell afterwards following treatment (P less than 0.05). Even in the absence of disease activity or during minor disease symptoms IL-2R levels were higher (P less than 0.01) than in healthy controls. Sixteen out of the 21 exacerbations (76%) were preceded by a significant increase in IL-2R. Changes in levels of anti-dsDNA and complement C3/C4 tended to precede changes in levels of IL-2R. We conclude that increased levels of IL-2R, compatible with T cell activation, are present in SLE already during inactive disease. These levels further increased prior to exacerbations of disease. As such, IL-2R is an indicator of disease activity in SLE. Serial measurement of IL-2R is a sensitive test for predicting disease exacerbations of SLE. PMID- 2208794 TI - Evidence for circulating activated cytotoxic T cells in HIV-infected subjects before the onset of opportunistic infections. AB - The activity of both cytotoxic T lymphocyte (CTL) and natural killer (NK) cells were measured cross-sectionally in 43 subjects seropositive for HIV, in 27 HIV- blood donors and in 24 HIV- persons from the Outpatients Clinic for sexually transmitted diseases. CTL activity was evaluated using the HL-60 cells coated with OKT3 as the targets and freshly separated peripheral blood lymphocytes as the effectors. In 20 out of 43 HIV+ subjects, CTL activity was significantly enhanced in comparison to the HIV- subjects. This lytic activity correlated positively with the percentages of CD3+ HLA-DR+, of CD8+ CR3- and of CD57+ CD16- lymphocytes, and was greatly reduced after elimination of CD8+, of HLA-DR+ or of CD57+ cells. The median CTL activity seemed to increase from CDC group II to CDC group IV (Centers for Disease Control classification), but to return back to control levels in those patients with a history of opportunistic infections. NK function in HIV+ subjects was not significantly different from that in the blood donors. In seropositive patients, NK activity correlated positively with the percentages of both CD16+ CD57+ and of CD8+ CR3+ cells and was strongly diminished after elimination of CD16+ or of CD57+ cells. There was no significant change in NK function according to the clinical stage. The data show that circulating CD8+ HLA-DR+ CD57+ T cells in HIV+ subjects are activated cytotoxic T cells and point to progressive (over) activation of this T cell compartment until the onset of opportunistic infections. PMID- 2208795 TI - Presence of antibodies against endothelial cells in the sera of patients with episodic angioedema and hypereosinophilia. AB - We reported three additional cases of a newly described syndrome called episodic angioedema with hypereosinophilia. In order to investigate its pathophysiological mechanisms, four parameters were concurrently investigated, including blood eosinophil density, serum chemoattractant activity, serum major basic protein (MBP) levels and the presence of anti-endothelial cell antibodies. Distribution of eosinophils through a metrizamide density gradient showed a preferential sedimentation of blood eosinophils in intermediate layers, clearly different from the hypodense cells (low-density layers) identified in a group of seven patients with idiopathic hypereosinophilic syndrome (HES). In two of the three patients with cyclic angioedema, a chemotactic activity towards eosinophils was detected in the serum (30 +/- 6 and 42 +/- 12 eosinophils per high-power field; P less than 0.05 compared with a control group). Serum MBP levels were at 1524, 619 and 1200 pg/ml. All three patients had circulating anti-endothelial cell antibodies, predominantly of the IgG isotype, in contrast to controls (P less than 0.01) or to patients with HES (P less than 0.01). Specificity of the antibody for endothelial cells was demonstrated in the three patients studied by the absence of binding to various blood cells, including monocytes, lymphocytes, eosinophils and platelets. In one case (patient 2), the levels of anti-endothelial cell antibodies, as well as the serum chemoattractant activity to eosinophils varied according to the successive acute phases of the disease. Although further investigations are needed to clarify the exact pathophysiology of this syndrome, and especially the possible participation of the anti-endothelial cell antibodies in the cutaneous lesions, these data suggest that angioedema observed in this syndrome could result from the combined effects of activated eosinophils and of immunologically induced endothelial lesions. PMID- 2208797 TI - Plasma and tissue interleukin-2 receptor levels in inflammatory bowel disease. AB - Plasma and tissue interleukin-2 receptor (IL-2R) levels were determined in patients with active ulcerative colitis and Crohn's disease. Compared with healthy controls (median 440 U/ml; range 240-900), significantly higher levels of plasma IL-2R were present in patients with active ulcerative colitis (median 1180 U/ml; range 580-7150; P less than 0.002) and Crohn's disease (median 1340 U/ml; range 480-9000; P less than 0.002). Compared with other laboratory parameters, plasma IL-2R levels were related most closely to clinical score of disease activity in Crohn's disease. Plasma IL-2R levels also reflected the clinical course and may provide a more accurate assessment of disease activity in Crohn's disease. In plasma of patients undergoing intestinal resection of active inflammatory bowel disease, raised levels of IL-2R were present in samples from mesenteric vein (draining inflamed intestine) compared with those from peripheral vein. In tissue homogenates of colonic biopsies, significantly higher levels of IL-2R were present in specimens from colons with active ulcerative colitis compared with healthy controls (median 230.2, range 20.7-581.5 versus 77.9, range 34.2-291.3; P less than 0.02). PMID- 2208796 TI - Sera with high levels of anti-smooth muscle and anti-mitochondrial antibodies frequently bind to cytoskeleton proteins. AB - Using ELISA methods, 54 sera from chronic active hepatitis (CAH) patients displaying high levels of anti-smooth muscle antibodies (SMA) and 18 sera from primary biliary cirrhosis (PBC) patients with high levels of anti-M2 antibodies were examined for the presence of high antibody levels against actin, tubulin, myosin, tropomyosin, troponin, vimentin and desmin. Our results showed that: (i) in CAH with high SMA activity, increased antibody levels were found in 51.9% of sera for actin, 31.5% for myosin, 35.2% for tubulin, 34.0% for tropomyosin, 11.3% for troponin, 22.6% for vimentin and 43.4% for desmin, compared with natural antibody levels in 21 normal sera; (ii) Similar high levels of these antibodies were found in the case of PBC; (iii) in most cases, sera simultaneously bound to several antigens of the panel; and (iv) approximately 26% of the CAH sera were found to be negative with the seven antigens examined while 22% were reacted with a cytoskeleton protein (CP) other than actin. These results indicate that current opinion associating SMA with anti-actin activity in CAH is confirmed for only 50% of cases and that although a good correlation between SMA and anti-CP antibodies can be obtained, there is still a significant percentage of SMA for which the putative antigen recognized needs to be determined. PMID- 2208798 TI - Noradrenaline sensitivity and calcium fluxes in arteries from rabbits with perinephritis hypertension. AB - 1. Contractions of isolated vascular and cardiac preparations taken from rabbits with perinephritis (one kidney, one wrapped) hypertension were compared with those of preparations from control operated animals. 2. Significantly increased sensitivity to noradrenaline, which acts on alpha 1-adrenoceptors, was found in mesenteric arterial rings but not in aortic rings. The degree of hypersensitivity was the same in the presence and absence of cocaine, suggesting that there is no increase in uptake of noradrenaline into adrenergic nerves in this model of hypertension. In contrast to these agonist-induced contractions, no increased sensitivity was found to potassium chloride, suggesting that hypersensitivity is specific for receptor mediated rather than membrane potential mediated effects. 3. No hypersensitivity to noradrenaline was found in the isolated left or right atria, which suggests that the hypertension is associated with changes in excitation-contraction coupling in blood vessels but not in cardiac muscle. 4. Hypertension increased basal 45Ca uptake in the mesenteric artery but not in the aorta. However, there was no significant difference between preparations from normotensive and hypertensive rabbits in 45Ca uptake or efflux stimulated by noradrenaline or KCl. 5. Increased basal 45Ca uptake could contribute to the increased sensitivity to noradrenaline found in the mesenteric artery in rabbit perinephritis hypertension. PMID- 2208799 TI - Influence of cardiac afferents on time-dependent changes in the renal sympathetic baroreflex of conscious rabbits. AB - 1. The stability of the renal sympathetic baroreflex and nasopharyngeal reflex, and the role of cardiac sensory receptors, was studied in conscious rabbits over a 5 h experimental period. 2. Renal sympathetic nerve activity (SNA) was recorded during (i) slow ramp changes in mean arterial pressure (MAP) of 1-2 mmHg/s induced by inflating perivascular balloon cuffs, and (ii) the inhalation of cigarette smoke. Experiments were repeated in other rabbits after blocking cardiac afferents with 5% intrapericardial procaine. 3. Baroreflex responses to the first two caval cuff inflations of the day were significantly greater than subsequent responses. After this, triplicate sets of reflex curves were relatively stable during a 2 h period in the morning. When the experiment was repeated in the afternoon, there was a significant attenuation of baroreflex range and a small fall in resting renal SNA which were abolished by pericardial procaine. 4. Changes in baroreflex properties were minimal when the reflex was assessed only twice, at the beginning and end of a 5 h period. No change was seen in the nasopharyngeal reflex whether the rabbits had been subjected to few or to many cuff inflations. 5. We conclude that time dependent changes can occur in the renal sympathetic baroreflex of conscious rabbits which must be allowed for by appropriate protocol design. These include increasing inhibitory influences from cardiac sensory receptors in experimental situations requiring multiple reflex estimations. PMID- 2208800 TI - Subsensitivity to ATP and some analogues in preparations of rat cauda epididymis and vas deferens after vasectomy. AB - 1. The effects of ATP and some of its more stable analogues have been examined upon preparations of epididymal and prostatic halves of vasa deferentia and of cauda epididymides from rats that had undergone vasectomy by medial transection of the vas deferens. 2. After unilateral vasectomy, the potencies of ATP, beta, gamma-methylene ATP and 5'-adenylylimidodiphosphate (AppNHp) in tissues ipsilateral to the vasectomy were decreased compared to tissues from the contralateral unoperated side of the animal. 3. Tissues from bilaterally vasectomized rats were less responsive to ATP when compared to tissues taken from sham-operated rats. 4. Tissues taken from rats which had undergone vasovasostomies following unilateral vasectomy remained less responsive to these purines. 5. Responses of cauda epididymides and epididymal halves of vasa deferentia taken from unilaterally and bilaterally vasectomized rats to alpha, beta-methylene ATP usually did not differ from those of respective controls. 6. It is proposed that the subsensitivity which develops to ATP and some of its analogues on the epididymis and vas deferens following vasectomy may reflect increased breakdown, perhaps associated with changes in structural integrity of the tissues, rather than with the sympathetic denervation which is associated with vasectomy. PMID- 2208802 TI - Evidence for the inhibitory effect of 5-hydroxytryptamine at central and peripheral sites on ovulation in rabbits. AB - 1. The effect of 5-hydroxytryptamine (5-HT) has been investigated on ovulation per se as well as on induced ovulation in rabbits. 2. 5-HT administered intracerebroventricularly (i.c.v.) did not induce ovulation per se. 3. The ovulation was induced by coitus, subcutaneous administration of progesterone and intravenous administration of cupric acetate. 4. Postcoital and progesterone induced ovulation was found to be blocked by i.c.v. administered 5-HT. 5. Cupric acetate induced ovulation was, however, not found to be blocked by i.c.v. administered 5-HT. 6. Intraperitoneal administration of 5-HT was found to block cupric acetate induced ovulation. 7. It is concluded that 5-HT exerts an inhibitory control over ovulation by acting at central as well as at peripheral sites in rabbits. PMID- 2208801 TI - Positive inotropic and vasoconstrictor responses to 14 beta-aminopregnane derivatives in isolated tissues from the guinea-pig. AB - 1. The objective of this study was to compare the positive inotropic and vasoconstrictor responses in guinea-pig isolated tissues of the aminosteroid derivatives LND 623 and LND 796 and the cardiac glycoside ouabain. 2. Ouabain ( log EC50, 6.66 +/- 0.04, n = 11) was more potent as a positive inotropic agent on guinea-pig right ventricular papillary muscles than either LND 623 (-log EC50, 6.26 +/- 0.08, n = 6) or LND 796 (-log EC50 5.66 +/- 0.05, n = 7). All compounds gave similar maximal increases in force of contraction. However, the ratio of the maximally effective concentration to the concentration giving 25% of the maximal response was approximately doubled for the aminosteroids compared with ouabain. 3. Ouabain (-log EC50 6.27), LND 623 (-log EC50 6.24) and LND 796 (-log EC50 5.43) produced slowly developing contractions of guinea-pig thoracic aortic rings. 4. These results indicate that, while the aminopregnane derivatives and ouabain produce qualitatively similar results, the therapeutic range for the positive inotropic responses is greater for the aminosteroids. PMID- 2208803 TI - Adhesion molecules on endothelial cells in the central nervous system: an emerging area in the neuroimmunology of multiple sclerosis. AB - The observation of lymphocyte adhesion/homing molecules with ligands (integrins and vascular addressins) on endothelial cells (EC) within target organs during a number of nonlymphoid chronic inflammatory conditions is occurring with increasing frequency. On the basis of evidence from the literature and pilot data on the localization of the putative vascular addressin for humans, HECA-452, in central nervous system (CNS) tissue, it is suggested that molecular recognition on CNS EC might play a pathogenetic role during immune-mediated demyelination in multiple sclerosis (MS). In one of six cases of MS, a case displaying a particularly malignant course, HECA-452 was specifically and reproducibly demonstrated on postcapillary venules in periplaque white matter beyond the zone of active inflammation. In the same case, CD8+ T cells predominated over CD4+ cells. In no case studied were EC positive for HLA-DR (Ia), in contrast to previous reports. Perivascular Ia positivity was common and was always associated with foamy macrophages or pericytes. In view of the occurrence of semiorganized lymphoid collections in a number of chronic inflammatory conditions, several of which are associated with expression of HEV markers, and in MS, it is concluded that examination of molecular recognition events on lymphocytes and EC within the CNS in MS is an area worthy of further study and an area with considerable therapeutic import. PMID- 2208804 TI - Sleep as a host defense: its regulation by microbial products and cytokines. PMID- 2208805 TI - Cerebrospinal fluid interleukin-6 activity in HIV infection and inflammatory and noninflammatory diseases of the nervous system. AB - Interleukin-6 (IL-6) activity was measured in the cerebrospinal fluid (CSF) of patients at different stages of human immunodeficiency (HIV) virus infection and of patients with multiple sclerosis (MS) or other inflammatory (OID) and noninflammatory neurological diseases (OND). In the advanced stages of HIV infection and in OID, IL-6 was detected more frequently (80 and 75% of the cases) and at higher concentrations than in the early stages of HIV infection. MS and OND (44, 48, and 44% of cases). Analysis of CSF and paired sera indicated that IL 6 production can be compartmentalized to either of the fluids. Evidence that altered blood-brain barrier functions can, at least in part, influence the CSF IL 6 levels was found in OID patients. No association was evident between intrathecal immunoglobulin synthesis and CSF IL-6 levels. Interleukin-1 (IL-1) levels were detectable in a minority of the samples from neurological patients; one OID patient had high levels of both CSF IL-1 and IL-6. PMID- 2208806 TI - A novel experimental model of giant cell myocarditis induced in rats by immunization with cardiac myosin fraction. AB - It is suspected that autoimmune disease processes are involved in the pathogenesis of a part of giant cell myocarditis. However, evidence for autoimmunity has rarely been demonstrated in clinical investigations. In this study, we have demonstrated a new animal model of autoimmune myocarditis characterized by the appearance of multinucleated giant cells. Lewis rats were immunized twice with human cardiac myosin fraction in complete Freund's adjuvant. Cardiac myosin fraction was prepared from the ventricular muscle of human hearts. Three weeks after the first immunization, acute and severe myocarditis was elicited in all rats. This myocarditis was characterized by massive pericardial effusion, enlargement of the heart, and gray discoloration of the cardiac muscle. Microscopically, there was marked cellular infiltration consisting of mononuclear cells, neutrophils, fibroblasts, and a considerable number of multinucleated giant cells. Extensive myocardial necrosis was also present. The heart weights increased from the third week to the fourth week and then gradually decreased. The titer of anti-myosin antibodies began to elevate from the second week and remained high until the sixth week. In the sixth week, inflammation became smoldering and the multinucleated giant cells disappeared. These findings indicate that the cardiac myosin fraction contains myocarditogenic antigen and that giant cell myocarditis can be induced by autoimmune involvement. To our knowledge, this is the first report of experimental giant cell myocarditis, which is closely similar to human giant cell myocarditis in its histology and clinical course. PMID- 2208807 TI - Experimental induction of systemic lupus erythematosus by recognition of foreign Ia. AB - A chronic GVH reaction induced in normal mice results in a syndrome that closely resembles SLE. In this study, we compared the autoimmune GVH syndrome induced in parent (C57BL/6Kh [B6] and B6.C-H-2bm12 [bm12]) and F1 [( B6 x bm12]F1) mice by transfer of parental spleen cells. A majority of the mice in all groups developed autoantibodies to chromatin and erythrocytes, and some of the mice also produced anti-dsDNA antibodies. The predominant isotype of the anti-chromatin autoantibodies was found to be IgG2a, although high levels of IgG2b antibodies were also present. Autoantibody production was in general more intense and more prevalent in parent----F1 hybrid combinations, compared to parent----parent infusions. No influence of host or graft gender was observed. These studies show that a chronic GVH reaction can be induced by both parent----parent and parent--- hybrid combinations. PMID- 2208808 TI - Heavy and light chain utilization in autoantibodies of elderly patients with systemic lupus erythematosus. AB - To determine whether age-related changes in immune function affect patterns of autoantibody production, we have examined the isotype and light chain utilization in autoantibodies of elderly patients with systemic lupus erythematosus (SLE). Enzyme-linked immunosorbent assays (ELISA) were used to determine the frequencies of IgG and IgM antibodies to single-stranded DNA (ssDNA), Sm, and the 70K protein component of RNP in the sera of 53 patients with SLE older than age 60. The IgG subclass distributions and kappa/lambda ratios for each of these autoantibodies were also determined and compared to measurements performed on the sera of 53 young adult patients with SLE. The frequencies of autoantibodies of each specificity, except IgM anti-ss DNA antibodies, were higher among the young adult patients, although the magnitudes of the responses were similar in both age groups. IgG anti-Sm antibodies were composed of both IgG1 and IgG2 subclasses, while IgG anti-70K RNP and IgG anti-ssDNA were predominantly of the IgG1 subclass. There were no differences in the IgG subclass distributions of any of the three autoantibodies between the elderly and young adult patient sera. The kappa/lambda ratios for each of the three autoantibodies were similar to that present in total serum immunoglobulins, and kappa/lambda ratios of autoantibodies, standardized to the kappa/lambda ratios of serum, were not different between elderly and young adult groups. Few patient sera of either age group (9 elderly, 7 young adult) demonstrated even midly skewed light chain ratios in their autoantibody responses. Thus, despite developing in an immunological environment that may have altered the clonality and isotype distribution of their responses, the autoantibodies produced by elderly patients with SLE were qualitatively similar to autoantibodies of younger patients. PMID- 2208809 TI - C5a-mediated release of interleukin 6 by human monocytes. AB - Recombinant human C5a (rC5a) was assessed for its ability to induce interleukin 6 (IL-6) production in human peripheral blood-derived mononuclear cell (PBMC) cultures. rC5a was observed to induce IL-6 production as measured by hybridoma growth promotion (B9.9 assay) and human B cell differentiation (SKW6.4 assay). Optimal IL-6 production was obtained after 24 hr stimulation with 0.1-0.5 micrograms/ml rC5a. In addition, natural human C5ades Arg and natural porcine C5a were able to induce a similar level of IL-6. The observed IL-6 activity appeared not to be due to endotoxin contamination since heat treatment (100 degrees C/15 min) inhibited rC5a induction of IL-6. The rC5a stimulation also induced an increase in steady-state IL-6 mRNA as determined by Northern blot analysis. Pretreatment of PBMC with leucine-methyl ester to deplete monocytes reduced the rC5a-induced IL-6 production to background levels. In addition, stimulation of purified T cell preparations with rC5a produced little IL-6 activity, suggesting that monocytes are the major source of IL-6 in this system. These results suggest that the inflammatory and immunoregulatory activities of C5a may in part be due to the stimulation of IL-6 release, a cytokine which possesses potent pleiotropic functions. PMID- 2208810 TI - Pemphigus foliaceus antigen: characterization of an immunoreactive tryptic fragment from BALB/c mouse epidermis recognized by all patients' sera and major autoantibody subclasses. AB - The pemphigus foliaceus antigen (PF Ag) is a 160-kDa desmosomal core glycoprotein, desmoglein I. A 50-kDa soluble immunoreactive fragment of the PF Ag was recently prepared from trypsinized cornified cell envelope preparations by papain treatment (R.S. Labib et al. 1989, J. Invest. Dermatol. 93, 272-279). This papain fragment (pf-PF) is associated with upper cell layers of the epidermis and appears to be trypsin resistant in situ. The present work describes the preparation of another fragment by trysinization of the viable lower cells of the epidermis of neonatal BALB/c mice. This tryptic fragment (tf-PF) is a 45-kDa glycoprotein that is partially purified by concanavalin A affinity chromatography of the trypsinization medium. The partially purified tf-PF preparation is capable of completely blocking the indirect immunofluorescence of high titer PF sera. The tf-PF is immunoprecipitated by all PF sera tested (n = 19) and by the two major subclasses of PF autoantibodies, IgG1 and IgG4. Autoantibodies of both the predominant IgG4 and the less prevalent IgG1 subclasses precipitate the same tf PF as demonstrated by a single compact spot of pI 5.5 by two-dimensional polyacrylamide gel electrophoresis. Chemical and immunological comparison of the tf-PF and pf-PF may explain why the acantholytic lesions of PF appear only in the upper epidermis, despite the presence of the PF Ag throughout all layers of the epidermis. The availability of these two soluble immunoreactive fragments of the PF Ag will be of great value for the further immunochemical characterization of the antigenic epitopes and their role in cell-cell adhesion. PMID- 2208811 TI - [Use of the ND-YAG laser in dental medicine]. PMID- 2208812 TI - [Church amid the village]. PMID- 2208813 TI - Academic administration: opportunities for advancement. PMID- 2208814 TI - The potential for prehospital thrombolytic therapy. AB - Several large trials of thrombolytic therapy have shown that treatment initiated in the first 1 or 2 hours following the onset of symptoms of acute myocardial infarction (AMI) is more effective than therapy started later in the course of illness. From our experience in three thrombolytic trials we concluded it would be difficult to reduce the total time from symptom onset to therapy without a major change in patient management. To accomplish this goal we have initiated MITI (Myocardial Infarction Triage and Intervention Project), a program for the prehospital diagnosis of AMI using specially trained paramedics, a checklist to establish eligibility for and contraindications to thrombolytic therapy, and a portable, battery-powered 12-lead electrocardiography (ECG) cellular telephone system that allows an electrocardiographic diagnosis to be made remotely by an emergency department physician. In the feasibility phase of MITI, 2,472 patients with chest pain of presumed cardiac origin were evaluated; 677 (27%) met the rigorous history and physical exam inclusion and exclusion criteria for potential thrombolytic therapy and had an ECG performed in the field. Of these ECGs, 522 were transmitted successfully by cellular telephone to a base station physician. Of the 522 patients, 107 had ST-segment elevation and met our criteria for initiation of thrombolytic therapy. Of the 2,472 patients with chest pain evaluated by the emergency medical technicians, 453 (18%) were diagnosed with AMI during hospitalization. Of these AMI patients, only 105 (23%) met the clinical examination and ECG criteria for pre-hospital thrombolytic therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2208816 TI - Thrombolysis: awareness of treatment and timing. A symposium. March 22, 1990, New Orleans. Proceedings. PMID- 2208815 TI - The earliest thrombolytic treatment of acute myocardial infarction: ambulance or emergency department? AB - Because the effectiveness of thrombolytic therapy is inversely related to the time interval before it is given, prehospital thrombolytic administration has been proposed and implemented to shorten the time between acute myocardial infarction (AMI) symptom onset and definitive therapy. Regardless of how effective these prehospital approaches prove to be, they have the potential to shorten the time to thrombolytic therapy in only a minority of the affected U.S. population because only approximately half of AMI patients are transported by the Emergency Medical Services (EMS) system. Preliminary efforts to shorten patient delay in response to AMI symptoms and to increase the number of patients who use the paramedic system have met with limited success. Other potential problems relating to prehospital thrombolytic administration include the high cost of electrocardiographic and communication equipment per ambulance, field drug stock cost and breakage, and additional medicolegal risks for physicians and prehospital providers. The medicolegal risk can be estimated by setting up a clinical decision analysis model. If prehospital treatment were to become standard care in the United States, half of the 1.5 million AMI patients per year (750,000) who are transported by paramedics would be candidates for prehospital treatment. Assuming a 30% treatment rate (225,000), a 5% major bleed and a 1% stroke complication rate, then 11,250 major bleeds and 2,250 strokes would occur in field-treated AMI patients. If we assume that the absence of physician screening might increase the incidence of complications between 1% and 10%, then 113 to 1,125 extra bleeds and 23 to 225 extra strokes would result from prehospital treatment compared with treatment in the emergency department (ED).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2208817 TI - Considerations for a national heart attack alert program. AB - Coronary heart disease (CHD) remains the leading cause of death in the United States--in women as well as men. In 1987, CHD was responsible for 512,138 deaths, of which 253,542 deaths were attributed to acute myocardial infarction (AMI) and accounted for over $43 billion in direct and indirect costs. The disease spares no one. Primary prevention is clearly important, but for those in whom primary prevention has not been applied or has failed, acting to minimize the effect of a heart attack is of paramount importance. Many of its victims do not obtain appropriate medical care, or obtain it too late for the latest lifesaving technologies to be effective. The goal of treatment is to prevent death and to salvage as much heart tissue as possible. To achieve this goal, it is essential to minimize the time from the first symptoms and signs to treatment. Opportunities exist at each phase of an evolving AMI to intervene promptly and appropriately to prevent sudden death and to preserve cardiac muscle and thereby reduce CHD morbidity and mortality. Yet, formidable problems also exist. These and other issues are presently being studied by the National Heart, Lung, and Blood Institute staff and advisors in consideration of whether to establish a national educational program aimed at reducing CHD morbidity and mortality through the rapid identification and treatment of those with AMI. PMID- 2208818 TI - Thoughts about PTCA and the problem of restenosis. PMID- 2208819 TI - Management of the patient following coronary thrombolysis. AB - Myocardial salvage can be maximized by the early institution of thrombolytic therapy and aspirin. Certain patients may benefit from the administration of intravenous heparin, beta blockers, or nitroglycerin. The routine use of percutaneous transluminal coronary angioplasty (PTCA) or calcium-channel blockers does not appear to be warranted. Recurrent myocardial ischemia should be vigorously treated with medical therapy and there may be value in cardiac catheterization, followed by PTCA or bypass surgery, depending upon the extent of myocardium at risk and the underlying coronary anatomy. Long-term morbidity and mortality may be reduced by instituting aspirin and beta blockers as well as by modifying risk factors. There is no evidence for the long-term benefit from any calcium-channel blocker. Oral anticoagulation may be warranted in those patients with a mural thrombus, congestive heart failure, or atrial fibrillation. ACE inhibitors may be of value in the presence of left ventricular dysfunction and certainly in the presence of symptomatic congestive heart failure. Antiarrhythmic therapy is generally indicated only for symptomatic or life-threatening arrhythmias. Residual myocardial ischemia should be sought by exercise testing, and those patients with poor exercise tolerance generally warrant cardiac catheterization in consideration for revascularization. PMID- 2208820 TI - Thallium-201 perfusion imaging with atrial pacing or dipyridamole stress testing for evaluation of cardiac risk prior to nonvascular surgery. AB - Preoperative assessment of cardiac risk using thallium-201 scintigraphy and atrial pacing (n = 42) or dipyridamole stress testing (n = 35) was performed in 77 patients (mean age 65 +/- 7 years), who subsequently underwent elective nonvascular surgery. All patients were at low cardiac risk by clinical criteria; none could perform exercise stress testing due to physical limitations. ST depression consistent with ischemia occurred in 11 patients during atrial pacing and in 1 patient during dipyridamole stress testing (p less than 0.01). Nine patients had reversible perfusion defects with atrial pacing, and 10 patients with dipyridamole stress testing; fixed defects were present in 15 and 8 patients, respectively. Only one patient (fixed perfusion defect with atrial pacing, left main disease on coronary angiography) underwent preoperative coronary revascularization. Two patients subsequently had postoperative cardiac events. One patient (reversible perfusion defect with dipyridamole stress testing) experienced sudden death after a nonvascular procedure, while a second patient (normal thallium images with dipyridamole testing) had a nonfatal myocardial infarction. In patients having atrial pacing or dipyridamole stress testing, thallium-201 scans that are normal or show only a fixed perfusion defect confirm a low risk of cardiac complications following nonvascular surgery. The presence of a reversible perfusion defect does not preclude a postoperative course free of cardiac complications in patients at low cardiac risk by clinical criteria. PMID- 2208821 TI - Infective endocarditis in the 1980s: experience at a heart hospital. AB - Three hundred episodes of infective endocarditis (IE) in 287 patients were studied from October 1978 to August 1986. The patients were in the age range of 0.2-78 (mean 30.76 +/- 16.06) years; 185 (68%) occurred in male patients. The etiologic agents were: Streptococci viridans group (93), enterococci (21), streptococci D group, nonenterococci (19), other streptococci (14), Staphylococcus aureus (59), Staphylococcus epidermidis (14), gram-negative bacteria (16), other gram-positive bacteria (16), fungi (4). Etiologic agents were not isolated in 52 (negative cultures). Valvular heart diseases occurred in 231 episodes, congenital heart diseases in 37, other heart diseases in 6. Sixty nine occurred in patients with prosthetic heart valves. In 69 there was no previous heart disease. Surgical treatment was performed in 102 episodes (37 with prosthetic valve IE and 65 with native valve IE); 22 patients (21%) died, 12 with prosthetic valve and 10 with native valve IE. The in-hospital mortality (medical and surgical patients) was 26% (78 patients). Long-term follow-up of 206 patients up to 7.1 (mean 2.13 +/- 1.68) years revealed that 26 patients died. Thus, IE remains a disease with high mortality and is fatal to a third of the patients, in spite of the progress in therapeutic methods. Its morbidity and mortality continues beyond the microbiological cure. PMID- 2208822 TI - Dynamic arm exercise during cardiac catheterization in the assessment of stenotic valvular disease. AB - Assessment of hemodynamic responses during some form of exertion or stress during cardiac catheterization is useful among patients suspected of having valvular stenosis who demonstrate normal or borderline valve gradients at rest. Leg raising exercise and drug administration are commonly used for this purpose, but each has inherent limitations. To evaluate the usefulness of dynamic arm raising exercise as a means of altering hemodynamics during cardiac catheterization, 23 such patients were studied. Measurements obtained during arm raising exercise were compared with those at rest. Heart rate rose by 34 +/- 4 beats/min (p less than 0.001), while cardiac output increased by 1.4 +/- 0.2 l/min (p less than 0.001). Stroke volume decreased slightly, although left ventricular filling pressures and pulmonary capillary wedge pressures rose in nearly all subjects. The change in valvular gradients was variable. These data were compared with those obtained in 11 similar patients receiving either dopamine or isoproterenol as an intervention. The changes in heart rate and cardiac output from the resting state were similar between the groups, with fewer side effects occurring during arm exercise. Dynamic arm exercise is a safe and effective maneuver which can be performed during cardiac catheterization in patients undergoing diagnostic evaluation of stenotic valvular disease. PMID- 2208823 TI - Comparison of atrial contribution to cardiac hemodynamics in patients with normal and severely compromised cardiac function. AB - The importance of atrial contribution to cardiac function in patients with congestive heart failure is controversial. Ten patients with severe congestive failure (Group A) and 10 patients with normal ventricular function (Group B) were studied during atrial and ventricular pacing. Left ventricular ejection fraction, baseline pulmonary capillary wedge pressure, and baseline cardiac index were different between Group A and Group B patients: 22 +/- 10 vs. 65 +/- 11 (p less than 0.01); 21 +/- 5 vs. 8 +/- 4, (p less than 0.01); and 2.8 +/- 0.5 vs. 3.5 +/- 1.0 (p = 0.05). Compared with atrial pacing, cardiac index decreased from 2.8 +/- 0.6 to 2.2 +/- 0.5 (p less than 0.01) in Group A and from 3.6 +/- 0.7 to 2.9 +/- 0.5 (p less than 0.01) in Group B, during ventricular pacing. Pulmonary capillary wedge pressure increased by similar amounts in both groups during ventricular pacing. The change in cardiac index, % change in cardiac index, and change in pulmonary capillary wedge pressure from atrial to ventricular pacing, were not different between Group A and Group B patients. By logistic regression analysis, no association was found between the % change in cardiac index and the following variables: left ventricular ejection fraction, left ventricular end-diastolic volume, baseline pulmonary capillary wedge pressure, change in pulmonary capillary wedge pressure, and baseline cardiac index. The atrial contribution to resting steady-state cardiac function is similar between patients with severe congestive failure and those with preserved ventricular function. PMID- 2208824 TI - Anatomic basis for and morphologic results from catheter balloon valvuloplasty of stenotic mitral valves. AB - This report provides the anatomic basis for catheter balloon valvuloplasty procedures. The morphologic hallmark of mitral stenosis is commissural fusion and the major mechanism of successful balloon valvuloplasty is commissural splitting. Single and double dilating balloons are used to increase the cross-sectional orifice area of stenotic mitral valves. Double balloons appear to improve the luminal diameter and cross-sectional area compared with single balloons. This report also illustrates the anatomic basis for single and double balloon catheter placement and position using the transseptal approach. PMID- 2208825 TI - Variant angina due to deficiency of intracellular magnesium. AB - A 51-year-old man was diagnosed as having variant angina by documentation of typical ST elevation during anginal attack and also by showing coronary arterial spasm (#2 and #12) during hyperventilation on coronary arteriography. Large quantities of calcium blocking agents and nitrates could not improve his symptoms. Lack of intracellular magnesium was suspected from a daily excretion of urine magnesium (5.3 mEq) and magnesium tolerance test (56.7%). After hourly infusion of magnesium sulfate (80 mEq), coronary spasm could not be induced by ergonovine. PMID- 2208826 TI - Embolic mononeuropathy in subacute bacterial endocarditis. AB - A 49-year-old man presented with temperature up to 39.5 degrees C, a sudden peroneal nerve lesion, and a cardiac murmur. The peroneal nerve lesion was likely caused by an embolic occlusion of an artery supplying the nerve. Until now, six cases of embolic mononeuropathy in endocarditis have been reported in the literature. Embolic mononeuropathy is a very rare manifestation of subacute bacterial endocarditis and quite often complicates, as do other more common embolic manifestations, the correct diagnosis. PMID- 2208827 TI - "Pseudo reinfarction": a consequence of electrocardiogram lead transposition following myocardial infarction. AB - Unexpected or bizarre new electrocardiographic changes should alert the physician to the possibility of lead transposition and, if in doubt, the electrocardiogram should be repeated. The classic form of limb lead transposition leading to the appearance of dextrocardia is well recognized. We report a patient with myocardial infarction where lead transposition led to a diagnosis of reinfarction and to the inappropriate use of thrombolytic therapy. PMID- 2208828 TI - Giovanni Maria Lancisi, 1654-1720. PMID- 2208829 TI - Effect of E. coli pyelonephritis on the intracortical accumulation kinetics of gentamicin and netilmicin in rats. AB - The role of serum levels on the intrarenal accumulation kinetics of gentamicin and netilmicin in normal and infected kidneys was evaluated in a short-term infusion model in conscious rats. Female Sprague-Dawley rats were infused over a period of 6 h with gentamicin and netilmicin achieving individual steady-state serum levels ranging from 0.5 to 120 micrograms/ml. The model of pyelonephritis used resulted in severe left pyelonephritis and mild right pyelonephritis. Only the right infected kidneys were studied. Gentamicin and netilmicin cortical concentrations were analysed as a function of serum levels by linear (least squares regression analysis) and non-linear regression. For the non-linear regression analysis, the Michaelis-Menten kinetic was the best fitting curve. Steady-state elevation of serum concentrations of gentamicin and netilmicin was associated with a non-linear increase of cortical concentrations in normal kidneys, suggesting a saturable process. By contrast, in the mildly-infected right kidneys, the steady-state elevation of serum concentrations of gentamicin was associated with a linear increase of cortical concentrations while the accumulation kinetic of netilmicin showed a saturable process. At lower serum levels (therapeutic range, from 0.5 to 15 micrograms/ml) both gentamicin and netilmicin showed a first order kinetics of accumulation and netilmicin accumulated less than gentamicin in normal kidneys (p = 0.0004). By contrast, the uptake of netilmicin was higher in the right infected kidneys, as compared to the uptake of netilmicin in the normal kidneys, (p = 0.00005), and as compared to gentamicin in the respective kidneys. We conclude that renal infection modifies the intrarenal accumulation of aminoglycosides. PMID- 2208830 TI - Remnant model of renal failure in the dog: avoidance of second surgery by chemical nephrectomy. AB - Experimental chronic renal failure in the dog is usually studied by a two-step surgical procedure. However, it is becoming increasingly difficult, due to animal welfare concerns, to get permission for such procedures in Canada. We describe a method for obviating the need for second surgery by injecting absolute alcohol into a renal artery, which leads to immediate functional nephrectomy. PMID- 2208831 TI - Human umbilical vein grafts as infrainguinal bypasses: long-term clinical follow up and pathological investigation of explanted grafts. AB - This retrospective study examines 105 consecutive infrainguinal bypasses using human umbilical vein (HUV) grafts as blood conduits over a 9 year period. In addition, 39 segments of these grafts were harvested at reoperation and submitted for morphologic, histologic, and scanning electron microscopy examinations. Fifty two below-knee femoro-popliteal and 53 femoro-distal bypasses were performed in 93 patients. Sixty-seven per cent of these bypasses were performed for either rest pain (18%) or gangrene (49%) and 29% were performed for acute ischemia. Primary and secondary patency rates were not statistically different and were 38% and 29% at 1 and 3 years respectively. Factors found to have a significant effect on patency were site of distal anastomosis, state of distal run-off, and indication for operation. Other complications requiring reoperation included aneurysm formation (8 cases), infection (6 cases), mural thrombus (2 cases), and stenosis (2 cases). Pathologic examination revealed a damaged luminal surface in 22 grafts, deep folds in 8 grafts and delamination of the graft wall in 16 cases. Bacteria were seen in the folds of the grafts and, in addition, the presence of bacteria was documented in 7 out of 26 clinically non-infected grafts. The combination of poor patency rates and pathologic evidence of biodegradative phenomena have led us to discontinue HUV as an arterial substitute. PMID- 2208832 TI - Distribution of saline following acute volume loading: postural effects. AB - The influence of posture on the transvascular partitioning of an acute isotonic saline load was studied in a large number of functionally nephrectomized anaesthetized dogs. In 10 supine dogs given Ringer's-lactate (7% body weight) over 30 min, there was significant protein efflux from the vascular space during the infusion interval accompanied by a 67% loss of infusate into the interstitial space. At the end of three hours, only 10.9% of the infusate remained within the plasma, representing 42% of the anticipated recovery. When animals were placed in their usual quadruped position, the acute saline load was accompanied by protein loss as previously, but there was in addition continuing protein loss into the interstitial space during the post-infusional period. At 3 h, only 5.1% of the infusate had been retained. Volume loading with dogs placed in the 45 degrees head-up tilt position produced zero net recovery of infusate and loss of original plasma so that at 3 h post-infusion, plasma volume had declined by 11% from control values. Tilting by itself for this time period had caused protein efflux without fluid loss. The application of lower body positive counter-pressure to dogs tilted up at 45 degrees improved the partitioning, so that instead of net loss, 13% of the expected volume remained within the vascular space. The provision of iso-oncotic colloid instead of saline prevented volume losses in supine but not tilted dogs. We conclude that the rapid infusion of isotonic solution is associated with augmented loss of protein into the interstitial space leading to diminished vascular retention of infusate. PMID- 2208833 TI - Vascular retention of saline following acute and subacute hemorrhage in dogs. AB - Acute hemorrhage is usually associated with compensatory mechanisms calculated to replenish the vascular compartment. In the present study, we studied the transvascular distribution of an isotonic saline load (7% body weight) delivered to supine anaesthetized dogs following acute (20-25 ml/kg blood removed on the morning of the study) or subacute (20-25 ml/kg blood removed 16-18 h before the study) hemorrhage. In 10 dogs subjected to subacute hemorrhage, plasma volume was unaltered from control values 3 h post-load, and 6/10 animals also lost original plasma volume. Only 5.8% of the anticipated volume was retained within the vascular space. The percentage of extracellular fluid (ECF) partitioned as plasma declined from 33 to 23% (p less than 0.05). In 6 dogs with acute hemorrhage treated the same way, plasma volume increased by 24% at 3 h post-loading and 59.8% of the available volume now remained intravascularly. The percentage of ECF partitioned as plasma declined from 30 to 26%, a change of only 13% compared to a decline of 30% observed for the subacute group. We conclude that a delay in replenishing the ECF following hemorrhage may profoundly alter the volume of infused isotonic saline retained within the vascular compartment. PMID- 2208834 TI - Immunochemical analysis of carbamyl phosphate synthetase I and ornithine transcarbamylase deficient livers: elevated N-acetylglutamate level in a liver lacking carbamyl phosphate synthetase protein. AB - Liver tissue from 3 patients with carbamyl phosphate synthetase I deficiency and 11 patients with ornithine transcarbamylase deficiency was analyzed by Western blots for the presence of carbamyl phosphate synthetase I and ornithine transcarbamylase cross-reactive material with anti-rat enzyme antibodies. One patient with carbamyl phosphate synthetase I deficiency had no cross-reactive material with the antibody to this enzyme, one had reduced amounts, and one had similar to normal amounts. Only one of the patients with ornithine transcarbamylase deficiency had apparently normal amounts of enzyme protein in his liver, another patient had markedly reduced amounts, and the other nine patients had traces or absence of reactive ornithine transcarbamylase protein. N acetylglutamate content in the carbamyl phosphate synthetase I deficient liver with absent enzyme protein, was higher (98.4 nmol/g) than that measured in 5 normal controls (41.6 +/- 19.3 mean +/- SD, n = 5) and much higher than the N acetylglutamate level (2.2 nmol/g) in another carbamyl phosphate synthetase I deficient liver with normal amounts of enzyme protein. Hepatic N-acetylglutamate content in 3 patients with complete ornithine transcarbamylase deficiency was below the normal mean but within 2 standard deviations from the mean (8.5-12.8 nmol/g) whereas it was higher (30.7 nmol/g) in another partial ornithine transcarbamylase deficient patient. Most patients with ornithine transcarbamylase deficiency have markedly reduced or undetectable enzyme protein in their liver, therefore. Western blot analysis could help to establish this diagnosis in most patients. Absent carbamyl phosphate synthetase I enzyme protein may have caused elevation of the hepatic content of its cofactor, N-acetylglutamate, by an as yet unknown mechanism. PMID- 2208835 TI - Platelet-mediated foam cell formation in atherosclerosis. AB - The early fatty streak lesions of atherosclerosis are characterized by the presence of cholesteryl ester-loaded macrophages or "foam cells." Platelets are also present in the early lesions of atherosclerosis and are often found in close association with foam cells. We have investigated the hypothesis that platelets contribute to foam cell formation by inducing macrophage cholesteryl ester accumulation. Using an in vitro culture system of human monocyte-derived macrophages and autologous platelets, we have demonstrated a platelet-dependent stimulation of macrophage cholesterol esterification and cholesteryl ester accumulation. The response is specific to platelets and is dependent upon activation of the platelets. An active fraction can be isolated from the releasates of thrombin-stimulated platelets that contain large cholesterol-rich platelet membrane vesicles. The results suggest that platelet-derived free cholesterol is required for platelet-induced macrophage foam cell formation. PMID- 2208836 TI - The role of lipoproteins and apolipoproteins in prediction of coronary heart disease risk. AB - Recent consensus conferences are recommending dietary intervention to lower serum cholesterol in a substantial portion of the population. These recommendations are based on analyses of serum cholesterol in clinical research laboratories which were under rigorous quality control. Sources of biological and analytical variation in serum cholesterol, which may be greater in the routine clinical laboratory or cholesterol screening programme than in a research laboratory, must be recognized by the physician and health care workers for effective use of the diagnostic information and monitoring of treatment procedures in a potentially large segment of the population. The estimation of lipoprotein cholesterol concentrations now offers a more precise measure of risk and should be considered for individuals at modest risk of premature cardiovascular disease on the basis of total cholesterol with a strong family history of cardiovascular disease but mild serum cholesterol elevations (5.2-6.2 mmol/L). The combined estimation of low and high density lipoproteins provides a more accurate estimate of cardiovascular disease risk than total serum cholesterol if the methodology for their estimation is under rigorous quality control. There is strong evidence that genetic variation in apolipoprotein structure provides a significant contribution to variation in serum cholesterol values. The two most common allelic apolipoprotein variants, apo E and apo (a), cause significant effects on serum cholesterol for a substantial portion of the population. Furthermore apo (a), which shows extensive sequence homology with plasminogen, may promote the deposition of lipoprotein (a) in the artery and interfere with fibrinolytic processes following inappropriate thrombus formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2208837 TI - Management of hyperlipidemia: goals for the prevention of atherosclerosis. AB - The goals of treatment for patients with hyperlipoproteinemia are to reduce plasma concentrations of known atherogenic lipoproteins, thereby exerting a favorable effect upon lipid deposition in the arterial wall and, less commonly, to prevent the adverse sequelae of hyperchylomicronemia in patients with severe hypertriglyceridemia. Diet is the cornerstone of the therapy after the exclusion of secondary factors; the decision to begin drug therapy should be made only after an adequate trial of diet has failed to achieve satisfactory concentrations of plasma lipids and lipoproteins. For patients without evidence of atherosclerosis the goals is to reduce the plasma concentrations of low density lipoproteins to below 160 mg/dl (4.2 mM/L); for those individuals with atherosclerosis or the concurrent presence of two risk factors, a lower level of LDL is desirable (less than 130 mg/dl; 3.4 mM/L). For regression to occur the LDL level may need to be below 100 mg/dl (2.6 mM/L). The bile acid sequestrants (cholestyramine and colestipol), nicotinic acid, fenofibrate, and inhibitors of HMG CoA reductase (e.g., lovastatin or simvastatin) are the most effective drugs for use in patients with primary hypercholesterolemia and these agents reduce plasma concentrations of total and LDL cholesterol by 15-45%. For those patients with concurrent hypertriglyceridemia, nicotinic acid, lovastatin or simvastatin, or fenofibrate are the preferred drugs for initial use. Fibric acid derivatives (e.g., clofibrate, gemfibrozil, bezafibrate, or fenofibrate) are all effective in the therapy of patients with type III hyperlipoproteinemia, as is nicotinic acid or lovastatin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2208838 TI - The influence of governmental decision-making on academic medicine: the Quebec experience. AB - Canadian medicine has achieved an appropriate balance between excellence in clinical practice and clinical investigation, making our academic system the best in the world. Adequately funded, universal medicine is the best and most equitable health care system ever devised. In Quebec both systems are failing because we are not a participatory democracy in which providers are consulted on decisions involving health care and education. Governmental decisions are made undemocratically, are based on dubious assumptions, and do not ensure patient flow from primary to tertiary institutions. The reduction in quotas for subspecialty residency posts and the two-year family medicine training requirement to obtain a GP's licence threatens to destroy academic medicine because we will be unable to produce sufficient numbers of specialists to populate our medical faculties, let alone conduct research. Concerted action by the Canadian Institute of Academic Medicine is essential if this catastrophe is to be avoided. PMID- 2208839 TI - Should Canadian medical schools care about the number of physicians they produce? AB - Physician manpower supply and potential oversupply have generated a great deal of interest in Canada in recent years, especially since increasing health care costs are considered by health care economists to be directly related to increasing physician numbers. The issue, however, is far more complex and deserves further scrutiny and detailed analyses. It is difficult to obtain an answer to even the simple question: how many physicians are in active practice? And many do not understand that there are multiple routes to entry to licensure. Changes in physician demographics, health care delivery systems, patient expectations, and medical advances will have a major impact on projections of future physician needs; and changes in physician numbers, undergraduate enrollments, and residency positions also have broad implications for the activities of medical schools and their affiliated teaching hospitals. For these reasons medical schools are and will remain essential elements in solutions of current issues and problems facing the health care sector. PMID- 2208840 TI - The uncertain future of Canadian academic medicine. AB - During the 1960's and 70's, academic medicine in Canada grew rapidly in size and scope and a number of research and clinical programs of the highest quality emerged. During the 1980's not only was this impetus not sustained, in some disciplines and regions there was likely a reversal of previous success. These adverse effects were produced by continued uncertainty and insufficiency of federal funding of research, underfunding of Canadian universities and of teaching hospitals, and by a decline within Canadian society of the images of both the physician and the teaching hospital with its technologically-based clinical and research programs. These negative influences were mitigated somewhat by the development during the 80's of more sources of research support from certain provincial governments and of a number of new biomedical research institutes and networks. The adverse influences of the 1980's will likely be perpetuated into the 1990's. Indeed an impending economic downturn and the return of constitutional disarray will worsen the climate for longterm growth in science and related health care research and technology. For Canadian academic medicine to survive these adverse influences, it must seek relationships and sources of support external to government. Most importantly however, it must strike new arrangements with provincial governments such that the imperatives of the academic health center and government become recognized in the planning process of the other party. For the academic health center this will mean involvement in government approaches to cost containment and health promotion; for provincial governments it will mean a commitment to health research and faculty renewal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2208841 TI - Symposium. Arthritis in childhood. PMID- 2208842 TI - Intertrochanteric corrective osteotomy in slipped capital femoral epiphysis. A long-term follow-up study of 26 patients. AB - The results of intertrochanteric corrective osteotomy in a series of 26 hips with moderate to severe chronic slipped capital femoral epiphysis are reported from follow-up studies in 1976 and 1986. In hips with a slippage of less than 40 degrees (ten hips), arthrosis was present in one hip. In the remaining 16 cases in which slippage exceeded 40 degrees, osteoarthrosis was present in 15, even though correction was adequate. From these observations it can be concluded that intertrochanteric corrective osteotomy does not prevent degeneration in cases with the most severe slip. On the basis of the present observations on treated and untreated cases, the authors advocate treatment by fixation without realignment, accepting the deformity in moderate and severe chronic slips. Rotational osteotomy may be considered in the event of hip joint contracture. PMID- 2208843 TI - Genetic aspects of juvenile chronic arthritis. AB - Immunogenetic studies in the past decade have confirmed the theory of an association between one's immunogenetic background and the manifestation of several forms of juvenile chronic arthritis (JCA), in particular pauciarticular onset JCA. Considerable work has been done at the serologic level to demonstrate disease association with the major histocompatibility Class II antigens in pauciarticular-onset JCA. The polygenic nature of JCA is best illustrated by the findings in this particularly well-defined clinical subgroup. Evidence is now emerging that analysis of the DNA sequence, the derived protein sequence, and the structure of Class II molecules will yield significant insight into the genetic predisposition to JCA. PMID- 2208844 TI - Cannulated blade plate for proximal femoral varus osteotomy. AB - Fixation of the osteotomy site in the proximal femur is technically demanding. A new system, which includes cannulated chisels and a cannulated one-piece plate that can be inserted over a guide wire, is suggested. The new system simplifies the procedure and provides stable fixation. PMID- 2208845 TI - Five-year postoperative results of cemented femoral arthroplasty in patients with systemic bone disease. AB - To determine whether bone cellular abnormality affects the results of cemented femoral arthroplasty, 21 patients had biopsies of the iliac crest and femoral cortex at the time of surgery. Roentgenographic and histomorphometric studies were used to characterize fibrous membrane formation, cancellous bone, calcar resorption, and bone turnover. Patients with high bone turnover and decreased femoral thickness and density before surgery were at risk of developing calcar resorption and cancellous diaphyses, conditions that weaken proximal stem support and lead to early failure. These findings suggest that noncemented stems may be indicated in this group. Another group, osteoporotic patients, suffered from osteoblastic insufficiency, which may be the indication for the use of cemented stems rather than noncemented stems, which require bony ingrowth. PMID- 2208846 TI - Porosity of various preparations of acrylic bone cements. AB - The total porosity and mean pore sizes of various bone cement preparations were measured using image analysis. The porosity in different commercial bone cements varied from 5% to 16% when these cements were prepared in the usual fashion. Centrifugation for 30 seconds resulted in a substantial reduction in the overall porosity of Simplex P, AKZ, Zimmer Regular, and CMW bone cements by reducing both the mean pore size and the number of pores per unit area. In contrast, the porosity of LVC, Palacos R, and Palacos R with gentamicin bone cements was not significantly decreased by centrifugation. Chilling the monomer before mixing resulted in higher porosity of both the centrifuged and uncentrifuged Simplex P, Zimmer Regular, and CMW bone cements. Simplex P mixed with chilled monomer and centrifuged for 120 seconds has one of the lowest porosities of the various cements, while retaining good handling characteristics and excellent fatigue strength. PMID- 2208847 TI - Trochanteric fractures. Influence of reduction and implant position on impaction and complications. AB - A review of roentgenograms and charts was made of 532 trochanteric fractures treated by the sliding-screw technique. According to Evans' modified classification, 65% of the fractures were unstable. There was no breakage or bending of implants. Twenty (3.8%) reoperations were performed because of technical complications or nonunion. The Singh index revealed more unstable fractures and technical complications in hips with Grades 1-3 than in hips with Grades 4-6. Reoperation was more frequent if the screw tip was within 8 mm from the subchondral line in the superolateral quadrant or in the anteroproximal quadrant than if the screw ended farther from the subchondral line. Fifty-five (10.8%) of the lag screws migrated 2 mm or more. Postoperatively, the neck-shaft angle decreased more in unstable fractures than in stable fractures. The decrease in neck-shaft angle was less when the proximal fragment impinged medially on the shaft fragment. Unstable fractures with this type of reduction also impacted less than hips with anatomic reduction or medial reduction of the shaft fragment. Weight bearing did not significantly influence the degree of impaction. PMID- 2208848 TI - Subtrochanteric fractures. A retrospective analysis. AB - In a retrospective review of 107 patients treated during an eight-year period for subtrochanteric fractures, the average follow-up period was 25.5 months (range, six to 96 months). Comparisons of fracture patterns, fixation devices, and complications of osteosynthesis were made in an attempt to identify fixation devices that are best suited for the treatment of this difficult orthopedic problem. The Seinsheimer system of classification was used, and the fracture at risk was identified. Long spiral fractures with associated butterfly fragments in the osteopenic bone of elderly patients occurred most frequently, with complications of osteosynthesis and inherent instability. Despite the theoretic biomechanical advantages offered by the intramedullary systems, follow-up observations showed better results in patients with treatment by extramedullary devices. PMID- 2208849 TI - The influence of joint line position on knee stability after condylar knee arthroplasty. AB - Using a special knee-testing device, ten knees obtained at autopsy were subjected to varus-valgus, anterior-posterior, and flexion-rotation analysis in the intact state and after total knee arthroplasty. The ten knees showed no significant change in stability after knee replacement when the joint line was maintained in its natural position. When the femoral component was repositioned 5 mm proximally and 5 mm anteriorly, a significant increase in laxity occurred during midflexion. When the joint line was shifted 5 mm distal and 5 mm posterior to its anatomic location, significant tightening occurred in midrange of motion. Coupled rotation of the tibia with knee flexion was decreased after surgery in all knees with no specific relationship to joint line position. Coupled rotation with varus-valgus testing, however, remained within the normal range through the first 30 degrees of flexion only when the joint line was restored to its normal anatomic position. Stability in condylar knee arthroplasty is in part dependent on position of the joint line. Surgical techniques that rely on restoring the flexion and extension gap without regard to joint line position may result in alteration of varus valgus or anterior-posterior displacement in midrange flexion. PMID- 2208850 TI - Suction drainage tube entrapment in total knee arthroplasty. AB - Two cases of entrapment of suction drainage tubes between the femoral and tibial components were encountered after total knee arthroplasty. The first patient had an arthrotomy because it was believed that the tube was caught in a suture, and while attempting to remove it a portion remained trapped in the joint. At operation, flexion of the knee released the tubing. The second patient did not require reoperation because flexion of the knee released the tubing. PMID- 2208851 TI - Effects of screws and a sleeve on initial fixation in uncemented total knee tibial components. AB - Aseptic loosening of tibial components remains a serious problem in uncemented total knee arthroplasties. Achieving rigid initial fixation of porous-coated components is one of the most important factors in promoting bone ingrowth. The results of a biomechanical study for micromovement of the tibial component under posteroanterior shear and axial compressive loading are presented. Forty anatomic specimen tibiae were stress tested on a servohydraulic mechanical test machine to evaluate the effects of screws and a sleeve on initial fixation of the uncemented total knee tibial component. Twenty specimens were used for posteroanterior shear loading and 20 for anterolateral axial compressive loading. Four cancellous screws were inserted through holes of the tibial tray to pierce the cortex of the proximal tibia. The methylmethacrylate sleeve was applied to the central stem. Rigidity of fixation was significantly improved by the combination of screws and a sleeve. Bone strength was also an important factor affecting the quality of fixation. PMID- 2208852 TI - The effect of screws and pegs on the initial fixation stability of an uncemented unicondylar knee replacement. AB - Two uncemented unicompartmental tibial components were examined for initial fixation stability. A conventional design that employed a single posteriorly angled peg was compared with a new design that was held in place by cancellous bone screws. The components were implanted into the medial condyles of 12 preserved human tibiae, and a cyclic load was first applied anteromedially and then posteromedially. The screwed implants failed at significantly higher loads (1634.8 +/- 121.6 N, mean +/- standard error of the mean) than the pegged implants (1103.3 +/- 152.0 N). On application of a 19.6-N preload, the screwed implants moved significantly less than the pegged implants. Although the differences in micromotion and subsidence were not always significant, there were definite trends. The screwed implants had much lower levels of temporary and permanent displacement compared with the pegged implants for all load levels from the initial load of 245.2 N up to and including the failure load. When the motion that resulted from moving the load from the anterior position to the posterior position was examined, the screwed implant's average total motion was less than 10 microns compared with almost 135 microns for the pegged implant after the 245.2-N load cycle. For the cycle before failure, the screwed implant's average motion increased to less than 29 microns, whereas the pegged implant's average total motion was almost 354 microns. From this information it appears clear that screws provide better initial fixation stability than angled pegs for uncemented unicondylar tibial components. PMID- 2208853 TI - The value of indium 111 leukocyte scanning in the evaluation of painful or infected total knee arthroplasties. AB - Evaluation of painful total knee arthroplasties (TKAs) for infection can be difficult. Indium 111 (111In) leukocyte bone scanning provides a minimally invasive technique for evaluation of possible infection. Thirty-eight patients with a painful TKA who had surgical exploration after 111In leukocyte scanning were reviewed. The scan had an accuracy of 84%, a sensitivity of 83%, and a specificity of 85%. The 111In leukocyte scans must be interpreted in conjunction with the clinical evaluation of the patient because they are less accurate for study of TKAs than of total hip arthroplasties. PMID- 2208854 TI - Pediatric spondyloarthropathies. AB - Seronegative spondyloarthropathies in childhood are often misdiagnosed as juvenile rheumatoid arthritis, but recognition of their distinct clinical manifestations and unique underlying pathophysiologies can aid in making a proper diagnosis. Ankylosing spondylitis, Reiter's syndrome, psoriatic arthritis, and the arthritis associated with inflammatory bowel disease are arthritides most often found in young adults, but they may also be present in children. Extraarticular manifestations include inflammation of the eyes, skin, gastrointestinal tract, and genitourinary tract associated with inflammation of the entheses. The proper diagnosis will allow for treatment regimens that differ from those usually used for juvenile rheumatoid arthritis. Early diagnosis and treatment often lead to an early recovery and a return to normal daily activities. PMID- 2208855 TI - Paradoxes in the history of the anterior cruciate ligament. AB - A historic review of anterior cruciate ligament (ACL) investigation reveals two important paradoxes. (1) Ideas and concepts recently proposed were first put forth much earlier. (2) Controversy regarding this ligament continues despite the increased amount of information available. Much of the recent ACL literature, although regarded as newly discovered, has its roots in far older, and apparently forgotten or overlooked, work. Examples include: (1) ACL intactness is best tested at full extension; (2) hemarthrosis and ACL rupture are closely associated; and (3) ACL rupture sometimes masquerades as a minor injury. Additionally, early investigators achieved notable advances in surgical techniques. These contributions disappeared from the literature for two major reasons. First, early investigators observed few patients, with typical practitioners rarely seeing ACL injuries, and consequently, little data existed to support their observations. Second, observations could not be confirmed until the advent of widespread, successful surgery. Undoubtedly, orthopedists now know much more about the ACL, yet many issues remain controversial. Does the ACL perform a vital function? What is the efficacy of operative versus nonoperative treatment? What are the relative merits of direct repair, intraarticular substitutes, and extraarticular nonanatomic procedures? The origins and continued existence of controversy stem from several sources, including the less than rigorous study design and the scarcity of natural history, long-term follow-up studies, and basic science studies. The perception of the ACL as a simple structural unit has also perpetuated this controversy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2208856 TI - The outcome of nonoperatively treated complete tears of the anterior cruciate ligament in active young adults. AB - The results of nonoperative treatment of 72 patients with complete anterior cruciate ligament (ACL) tears, documented by examination under anesthesia and arthroscopy, were evaluated. All patients had an acute injury with hemarthrosis in a previously normal knee. Patients having meniscal repair were excluded as were those with collateral or posterior cruciate ligament tears or associated fractures. Treatment in all cases consisted of a standard protocol of early rehabilitation and bracing. A detailed rating of symptoms and function was performed at an average of 38 months postinjury (range, eight to 84 months). Overall results were 11% excellent, 20% good, 15% fair, and 54% poor. Thirty-five percent had ACL reconstruction during the follow-up period. Results indicate that young adults who return to a vocation requiring strenuous physical activity frequently can expect unsatisfactory results after nonoperative treatment of an acute complete tear of the ACL. PMID- 2208857 TI - Isolated avulsion of the biceps femoris insertion. A case report. AB - The clinical, roentgenographic, and operative findings of an isolated biceps femoris avulsion in a 21-year-old man demonstrated the significance of the static stabilizers about the knee, menisci, and articular cartilage. Examination of the dynamic structures about the knee, however, may present a diagnostic problem. A systematic examination of the musculature (hamstrings, quadriceps, and patellofemoral mechanism) should be included in the evaluation of every acute knee injury. Special attention should be given to the surface anatomy as well as function of the knee. PMID- 2208858 TI - Factors influencing the results of open reduction and internal fixation of tibial plateau fractures. AB - Forty-three displaced tibial plateau fractures were treated with open reduction and internal fixation. The fractures were classified into four groups, and the clinical results were evaluated using a standard 100-point knee rating system. The average follow-up period after surgery was 2.7 years. Overall there were 35 excellent, five good, three fair, and no poor results. In five of eight knees with a less than excellent score, the results were due to the technique of fracture fixation or the absence of a bone graft. There were ten postoperative complications, but only one ultimately affected the clinical result. Fourteen patients required removal of implants. Roentgenographic analysis showed that six knees had mild degenerative changes, two had moderate, and two had severe degenerative changes. There was no statistically significant association between the fracture type and a less than excellent result. The absence of bone grafting, however, was associated with a less than excellent result. Bicondylar fractures had a mean range of motion of 110 degrees, 18 degrees less than that of all other types of fracture combined. PMID- 2208860 TI - In vivo osteochondrogenic potential of cultured cells derived from the periosteum. AB - Periosteal cells were isolated from young chicks, introduced into cell culture, subcultured, and then inoculated into athymic, nude mice to test the in vivo osteochondrogenic potential of cultured periosteal cells. In monolayer cultures, the adherent periosteal cells showed fibroblastlike morphology and overtly expressed neither osteogenic nor chondrogenic phenotypes. Cultured cells inoculated heterotopically into nude mice eventually gave rise to bone tissue at the subcutaneous injection site. The process of bone formation occurred through two different mechanisms: intramembranous bone formation at the peripheral portion of the inoculum early and endochondral bone formation in the central portion later. Frozen, preserved periosteal cells also formed bone after introduction into nude mice in the same temporal histologic sequence as the unfrozen cells. Cultured chick muscle fibroblasts from donors that were the same age as controls did not form bone or cartilage when inoculated under identical conditions to those of cultured periosteal cells. These results suggest that periosteum of young chicks contains subsets of progenitor cells that possess the potential to differentiate directly into osteoblasts or chondrocytes when inoculated in vivo. Importantly, this potential is retained after enzymatic isolation, cell culture, subculturing, and freeze preservation. PMID- 2208859 TI - A ten-year review of treatment of delayed union and nonunion with an implanted bone growth stimulator. AB - A ten-year clinical and roentgenographic review was conducted on the patients in the original Australian multicenter trial that evaluated use of an implantable bone growth stimulator for delayed union and nonunion. Of the original 81 patients, 38 patients were located, seven patients had died from unrelated causes, and 36 were unlocatable. Of the 38 patients located, 37 patients (representing 38 fractures) participated in a detailed clinical review and had a roentgenographic assessment. All fractures had remained united, and normal bone remodeling had occurred. There were no adverse effects of the generator or cathode wire. Six patients initially reported as failures had healed after further surgical intervention. Thus, normal osteogenesis occurs in association with electrical stimulation using an implantable bone growth stimulator. This ten year review supports the long-term safety and effectiveness of this technique in treating nonuniting fractures. PMID- 2208861 TI - Immunologic abnormalities of juvenile arthritis. AB - Many immunologic abnormalities have been found in children with all forms of chronic arthritis, but few are clinically useful or well understood. However, in children with arthritis it is important to distinguish among those with rheumatoid factor, antinuclear antibodies, or hypogammaglobulinemia. Rheumatoid factor is specific for adult-type rheumatoid arthritis; the presence of antinuclear antibodies increases the likelihood that the child may develop uveitis; and hypogammaglobulinemia may be associated with complicating infections. Other unusual antibodies, autoantibodies, antigen-antibody complexes, and complement activation products are found in children with arthritis, but none of these define a diagnostic or consistent group of diseases. Similarly, changes in the numbers of immunologically active cells and regulating mechanisms occur but not in specific patterns. As yet, none of the known immunologic abnormalities explain the pathogenesis of these diseases and only a few appear disease specific. PMID- 2208862 TI - The relationship between bone morphogenetic protein and neoplastic bone diseases. AB - The monoclonal antibody against bovine bone morphogenetic protein was used for demonstration of bone morphogenetic protein (BMP) in neoplastic bone diseases. The avidin-biotin-peroxidase complex method demonstrated that BMP mainly exists in the cytoplasm of tumor cells of osteosarcoma and chondrosarcoma. Immunostaining showed that a majority of osteosarcomas and all of the chondrosarcoma cells contained a large quantity of BMP. Conversely, none of the fibrosarcomas showed positive staining. Thus, it was possible to differentiate osteosarcomas from fibrosarcomas by immunostaining. In fibrous dysplasia of bone, BMP was abundant in the fibrocellular tissue that had osteogenic activity. In contrast, fibrous tissue of ossifying fibroma showed weak positive staining; only the osteoblasts rimming the bone showed a positive reaction. Immunostaining showed that BMP was also detected in other neoplastic bone diseases such as osteoma, chondroma, and other tumors. PMID- 2208864 TI - The influence of growth hormone on the reversibility of articular cartilage degeneration in rabbits. AB - Growth hormone has chondrogenic affects on normal as well as on damaged articular cartilage. In this study, the influence of growth hormone is investigated on early degenerative changes in the articular cartilage in 72 New Zealand white rabbits. Cartilage lesions were created in femoral condyles using an immobilization model. Cartilage damage was assessed using biochemical, histologic, and biomechanical criteria. Growth hormone had no influence on prevention of immobilization abnormalities but had a significant affect on healing of established lesions. PMID- 2208865 TI - Effects of corticosteroids on mechanical strength of intervertebral joints and vertebrae in dogs. AB - Dogs with hyperadrenocorticism had a higher incidence of intervertebral joint disease, i.e., disc protrusion or spondylosis. In comparing cases of hyperadrenocorticism with age- and breed-matched controls with hypothyroidism, the incidence was significantly greater than expected. This was not seen, however, in beagle dogs in which the incidence was already high and attributed to chondrodystrophoid tendencies in this breed. To investigate the pathogenesis of this association and its possible relationship to steroid-induced osteopenia, adult dogs were given a placebo, prednisone, or prednisone plus calcium for six months. Torque testing of intervertebral joints revealed a consistent trend of lower force to failure in both prednisone-treated groups, but the difference was not statistically significant. In these dogs with mild to moderate hyperadrenocorticism, compression tests of intact vertebral bodies were not significantly different, but blocks of trabecular bone cut from the vertebral bodies failed at significantly lower compressive forces in both prednisone treated groups compared with controls. Histomorphometric evaluation of lumbar vertebral trabecular bone revealed that the percentage of bone volume was not significantly decreased in the prednisone-treated groups. Nor was there any difference in the thickness or porosity of vertebral end-plates, which might contribute to weakening of intervertebral ligamentous insertions. PMID- 2208863 TI - Influence of postmortem time and temperature on osteoinductive activity of demineralized microperforated ethylene oxide-sterilized syngeneic bone implant in the rat. AB - Bone morphogenetic protein is labile and easily inactivated by many extracorporeal factors. It is crucial to establish whether delay in retrieval of donor bone and ambient holding temperature of the donor body influence osteoinductivity of bone left in situ. Of ten adult rats that were killed, five were kept at 4 degrees and five at room temperature. Femurs were harvested at 24, 36, 48, 72, and 168 hours. After processing, segments were implanted in 20 four week-old syngeneic rats for 14 days. The level of osteoinduction was evaluated histologically. It was excellent in the 4 degrees group in the 24-, 36-, and 48 hour specimens but less advanced at 72 hours. Bone taken from the room temperature group showed findings identical to those kept at 4 degrees through 36 hours, but osteoinduction was less advanced at 48 hours and absent at 72 hours. No bone formed at 168 hours in either temperature group. The following observations were made. (1) Osteoinductivity of demineralized bone left in situ after death was unexpectedly stable. (2) Retrieval time was extended by donor cooling. (3) Microperforated demineralized bone actively induced new bone formation. (4) Ethylene oxide does not inhibit osteoinduction when correctly applied for sterilization. If confirmed in humans, retrieval of bone to be used for osteoinduction could be delayed for some hours, particularly if the donor was immediately refrigerated. This would increase the effective number of bone tissue donors and utilize an undeveloped resource. PMID- 2208866 TI - Biomechanical comparison of single- and double-pin fixation for acute slipped capital femoral epiphysis. AB - Biomechanics of pin fixation for acute slipped capital femoral epiphysis (SCFE) was studied in an in vitro immature canine model. Acute SCFE were created in 24 paired femurs. The paired specimens were pinned with either one or two pins and loaded to failure. Strength and stiffness of the paired limbs were expressed as percentages of the loads necessary to create the initial SCFE in the intact specimen. Strength and stiffness were equivalent statistically for the intact physis and the fractured physis fixed with two pins. Single pinning was only 83% as strong and 78% as stiff as the intact physeal plate. Double-pin fixation is recommended over single-pin fixation for acute SCFE. These data, however, should not be extrapolated to the clinical situation of fixation for chronic SCFE. PMID- 2208868 TI - Results of treatment of tibial and femoral osteomyelitis in adults. AB - From January 1, 1971, to December 31, 1985, 425 patients with chronic osteomyelitis of the femur or tibia were seen at the authors' institution. The success rate in this recent experience was 84.4% compared with 50.9% in the authors' results published in 1970. A classification of chronic osteomyelitis is as follows: (1) hematogenous osteomyelitis; (2) osteomyelitis in united fractures (fracture with union); (3) osteomyelitis in nonunion (fracture with nonunion); and (4) postoperative or posttraumatic osteomyelitis in which bone was not fractured. For management of the scarring of surrounding soft tissue, there has been a change to excision of the scarred tissue and reliance on muscle flap, free tissue transfer, or closure of soft tissues without irrigation with antibiotic solution. In recent years, free microvascular osseous grafts have permitted more aggressive resection of the involved osseous tissue. The predominance of gram negative organisms and penicillin-resistant Staphylococcus aureus and the occurrence of methicillin-resistant S. aureus continue. PMID- 2208867 TI - Biomechanical factors in the metaphyseal- and diaphyseal-lengthening osteotomy. An experimental and theoretic analysis in the ovine tibia. AB - A post hoc comparison of the mechanical factors that affected the outcome of experimental metaphyseal- and diaphyseal-lengthening osteotomies in sheep tibiae was performed. The resulting motions between bone segments at the metaphyseal and diaphyseal levels were estimated using measured fixator stiffnesses, postural muscle activity, ground reaction forces, and calculated internal and external loads. Relative displacements of bone segments of up to 2.8 degrees were estimated in postural activities; displacements were up to 4.9 times larger at the metaphyseal than at the diaphyseal osteotomy level. The results suggest that due to these increased motions, mechanically inferior conditions for healing at the metaphyseal-lengthening osteotomy level may counteract any supposedly superior biologic healing potential that the metaphyseal region of the bone may have compared with the diaphyseal region. These results correlate well with the clinical findings of the earlier animal study. PMID- 2208869 TI - The martyrdom of Doctor Andreas Vesalius. AB - The development of modern medicine began in the 16th century when Dr. Andreas Vesalius overthrew the previously uncontested medical dogma of the Greek physician Galen. Medical progress had been hindered for more than a millennium by strict adherence to Galen's authority. Flemish-born Vesalius challenged the political and societal forces of the time. At the University of Padua, he studied and later taught human anatomy by performing dissections. His discoveries were published in 1543 in his monumental De Humani Corporis Fabrica. Controversy led to his resignation from the University of Padua. His magnum opus was interpreted as a challenge to both academia and the church. He went to Spain, where he served as personal physician to Emperor Charles V. After almost 20 years in Spain, he became involved in an unfortunate incident that incurred the condemnation of the Inquisition. The royal court's intervention saved Vesalius from being burned at the stake, however, and he was ordered to make a pilgrimage to Jerusalem to atone for his error. On the return voyage, he became ill and died on the Greek island of Zante. PMID- 2208870 TI - Soluble mediators of articular cartilage degradation in juvenile rheumatoid arthritis. AB - Juvenile rheumatoid arthritis (JRA) involves a wide range of joint tissues. Tissue changes include proliferation of synovial cells, alterations in synovial fluid, and degradation of articular cartilage. Synovial cell proliferation results in increased numbers of fibroblasts and lymphocytes. Changes in the synovial fluid include increased content of antibodies, altered complement ratios, increased levels of factors stimulating cartilage-mediated proteoglycan degradation, and decreased levels of insulinlike growth factor I. Levels of cytokine such as interleukin-1 and interleukin-2 vary with cell culture and assay technique. Cartilage degradation is apparent from increased quantities of proteoglycan and glycosaminoglycan in serum and synovial fluid. Type II collagen peptide antibodies are also prevalent in JRA patients. Cartilage degradation appears linked to factors in JRA synovial fluid. Conditioned medium of peripheral blood mononuclear cells from patients with JRA also stimulates increased release of cartilage proteoglycan. Thus, the outcome in JRA likely reflects activities of interacting soluble factors that directly influence cartilage homeostasis. PMID- 2208871 TI - Animal models of chronic inflammatory arthritis. AB - The use of animals has been indispensable to the investigation of the etiology, pathophysiology, and treatment of juvenile arthritis. Because of ethical concerns about studying children, the difficulty of obtaining tissue, and the heterogeneous manifestations and protean course of chronic arthritis in childhood, the scope of potential research has been severely limited. This brief review summarizes a few of the animal models most commonly used in chronic inflammatory arthritis research: subcutaneous air pouch, antigen-induced (including arthritogenic infectious agent), and spontaneous models. In the spontaneous and antigen-induced animal models of arthritis, local and systemic immunoregulatory abnormalities clearly play a major role in the pathogenesis of arthritis. By elucidating the immune response to those antigens, as well as the role of genetics and environment, the pathogenesis of juvenile rheumatoid arthritis may be better understood. At the present time, however, the complexity of these models precludes more definitive interpretation and extrapolation to human diseases. PMID- 2208872 TI - On a form of chronic joint disease in children. 1896. PMID- 2208873 TI - Growth abnormalities in children with juvenile rheumatoid arthritis. AB - Growth abnormalities in juvenile rheumatoid arthritis can be divided into two groups: local and systemic. Local disorders of growth often result in increased bone length and bone age or in marked decreases in longitudinal growth due to immobilization, premature epiphyseal closure, or fusion. Common growth defects seen in the knee, hand, wrist, hip, spine, and jaw are discussed. Systemic growth delay is most commonly secondary to active disease or treatment with corticosteroids. Nutritional aspects such as decreased appetite, reduced caloric intake, metabolic caloric requirements greater than available intake, or lack of essential vitamins could be the cause for decreased weight and stature. PMID- 2208874 TI - Ocular complications of rheumatic diseases of childhood. AB - The association between inflammatory ocular and articular disease is a strong one, although the pathogenesis of this relationship is obscure. For the physician or surgeon caring for children with chronic arthritis, awareness of the risk of chronic asymptomatic anterior uveitis is essential if early diagnosis, treatment, and prevention of visual impairment are to be accomplished. This is particularly true for children with pauciarticular-onset juvenile rheumatoid arthritis or psoriatic arthritis. Acute symptomatic anterior uveitis is characteristic of disorders such as ankylosing spondylitis. Whereas this disease is initially more unpleasant for the child, it has a good long-term prognosis. PMID- 2208875 TI - Medical treatment of juvenile arthritis. AB - The range of medications available to treat juvenile arthritis has markedly expanded over the past 15 years. Multiple new nonsteroidal antiinflammatory drugs (NSAIDs) are available in the United States, although only a few are approved for use in children, and none have been proven to be significantly better than aspirin in suppressing inflammation. The average time before significant improvement is noticed is over 30 days in the 50% of the children who respond to any NSAID within three months. The percentage of responders progressively increases with the length of therapy, so treatment should be continued until one is reasonably certain that improvement will not occur before changing medication. In the more severely involved child, gold and other disease-modifying medications are used. However, it has been difficult to prove the value of these medications in controlled studies because of the high rate of significant improvement in the control group treated with NSAIDs. In preliminary studies, methotrexate appears to have significant benefit in children who have failed other treatments. Other newer therapies, such as intravenous gammaglobulin, have only been used in a small number of patients and have not as yet been proven beneficial. PMID- 2208876 TI - The surgery of juvenile chronic arthritis. An overview. AB - Surgery now has a well-established place in the management of childhood arthritis. However, satisfactory results can only be achieved by a team of medical experts composed of a pediatric rheumatologist, an orthopedic surgeon, an anesthetist, a physiotherapist, and others who are knowledgeable about the particular problems of juvenile chronic arthritis. An aggressive team approach offers the best available help. PMID- 2208877 TI - A three-year retrospective study of synovectomies in children. AB - The aim of this study was to evaluate the results of synovectomies in children with juvenile arthritis. Five hundred twenty-eight synovectomies and tenosynovectomies were performed over a period of 13 years. The patients were followed for one, two, three, five, and ten years postoperatively. The evaluation after three years was chosen as the basis for this article. One hundred twenty five children with arthritis who were not evaluated three years postoperatively had less severe arthritis, both locally and generally, than the evaluated group of 389. The rate for good results and tolerability was high at one, two, and three years postoperatively but decreased with time; more patients went from good results to poor rather than vice versa. Global assessment, soft-tissue swelling, and limitation of movement seemed to be the best parameters for evaluating the results of synovectomies. It appears necessary to wait at least three years to evaluate the long-term effect of synovectomies. PMID- 2208878 TI - Total hip and knee arthroplasty in juvenile rheumatoid arthritis. AB - Total hip or knee arthroplasty is indicated in patients with juvenile rheumatoid arthritis when there is marked functional impairment and/or severe disabling pain from advanced structural hip or knee joint involvement. Relief of pain and dramatic improvement in function can be achieved in most patients. When both the hip and knee are involved, hip arthroplasty should probably be done first. Regional anesthesia is preferable. Careful preoperative planning is essential because custom prostheses are often required. Small bone size, osteoporosis, and soft-tissue contractures make the surgery technically demanding. Skeletal immaturity is not an absolute contraindication to surgery. Component loosening is the most frequent late complication in hip arthroplasty. It is less common in condylar metal-to-plastic knee arthroplasty in which patellar complications predominate. Cementless arthroplasty has an evolving role in the patient with juvenile rheumatoid arthritis and, to date, is more often used in the hip than in the knee. PMID- 2208879 TI - Combined laminoplasty and posterolateral fusion for spinal canal surgery in children and adolescents. AB - Spinal deformities, especially kyphosis and instability, after laminectomy for tumors and other diseases, are major clinical problems. Since 1981, combined laminoplasty and posterolateral fusion for the prevention of postlaminectomy spinal deformities was performed on eight male and two female patients aged two to 26 years (average, 13.9 years). The follow-up period was from six months to seven years and three months (average, three years and five months). Two patients died six and ten months postoperatively because of brain metastases (astrocytoma) and lung metastases (neuroblastoma), respectively. Good alignment with no instability of the cervical or thoracic spine was obtained for all patients, including the two who died. Laminoplasty combined with posterolateral fusion was found to be very effective in preventing the development of spinal deformities after spinal canal surgery for spinal cord tumors or other diseases in children and adolescents. PMID- 2208881 TI - Expectoration in the gastrointestinal tract. A diagnostic problem in In-111 granulocyte scintigraphy. AB - Scintigraphic detection of infectious foci with In-111 labeled granulocytes or leukocytes is a well-established technique in nuclear medicine. The technique is commonly used to demonstrate inflammatory activity in Crohn's disease and ulcerative colitis. Its application, however, may be influenced by infectious expectoration located within the gastrointestinal tract. In performing this technique, it is important to have this differential diagnostic possibility in mind; it can be clarified by repeated imaging. PMID- 2208880 TI - Tc-99m labeled leukocytes in imaging of patients with suspected acute abdominal inflammation. AB - One hundred patients with suspected acute abdominal inflammation were imaged at 0.5, 2-3, 4-6, and 24 hours after the administration of Tc-99m HMPAO labeled autologous leukocytes. Scan findings were retrospectively compared with final diagnosis, serum C-reactive protein (CRP), and antibiotic treatment. Clinical findings were confirmed with surgery, barium enema, or sigmoidoscopy in 61 patients, and diagnosis was based only on clinical findings in 13 patients. In 26 patients, symptoms subsided before a final diagnosis was made. Tc-99m leukocyte images were positive in 45 of the 61 patients with a confirmed diagnosis, including all patients with acute cholecystitis (N = 4) and inflammatory bowel disease (N = 8). They were also positive in nineteen out of 25 patients who had acute colonic diverticulitis and in 6 out of 7 who had intra-abdominal abscesses. Abnormal activity was found in patients with colonic carcinoma, small bowel infarction, and acute appendicitis. Abnormal activity was visualized in 0.5-hour images in all but one of the positive cases. With the exception of two postoperative cases, malignant lymphoma, and a liver abscess, a CRP level of greater than 75 mg/L was associated with positive image findings. Antibiotic treatment did not affect imaging findings. Imaging with Tc-99m labeled leukocytes appears to be valuable for detecting and localizing abdominal inflammation, and three-phase imaging during the first 4-6 hours is recommended. In some cases, 24 hour images may be useful for distinguishing small bowel from large bowel inflammation. PMID- 2208882 TI - Diminished response to furosemide in I-123 Hippuran renal studies of renovascular hypertension caused by unilateral renal artery stenosis. AB - Dynamic I-123 Hippuran renal studies to measure furosemide response (FR) were performed in three groups of patients: 1) 57 patients with renovascular hypertension due to a poststenotic, ischemic kidney; 2) 23 patients with essential hypertension; and 3) 50 nonhypertensive patients with healthy kidneys (control group). FR was observed as renal parenchymal tracer washout within 10 minutes after the injection of 40 mg of furosemide. The retention index (RI) took into consideration the renal parenchymal tracer content before and 10 minutes after furosemide injection. In the control group, the FR was greater than 50% and the RI was less than 20. Patients with essential hypertension revealed no differences in the amounts of FR and RI compared with the control group. In renovascular hypertension, the FR was diminished and the RI was raised significantly. The values of FR and RI showed a good correlation to the degree of the renal artery stenosis before and after percutaneous transluminal angioplasty. It is concluded that the stimulation of diuresis with furosemide and its quantification represent an important additional step in the evaluation of dynamic I-123 Hippuran studies to detect renal ischemia. PMID- 2208883 TI - I-123 hydroxyiodobenzyl propanediamine (HIPDM) cerebral blood flow imaging demonstrating transtentorial diaschisis. AB - To assess the clinical significance of transtentorial diaschisis (TTD) as demonstrated by I-123 HIPDM brain imaging, SPECT and/or planar images of 35 patients with stroke, 26 patients with Alzheimer's disease (AD), 2 patients with Creutzfeldt-Jakob disease (CJD), and 1 patient with a schizoaffective disorder were analyzed. TTD was observed in 21 of the 35 patients with strokes. In 13 stroke patients, TTD was associated with large infarcts in the middle cerebral artery (MCA) territory; in the remaining 8 stroke patients, TTD was associated with internal capsule and/or basal ganglia infarcts. TTD was not associated with small occipital or parietal infarcts. Despite cortical perfusion decrements, TTD was not seen in the AD patients, the CJD patients, or the patient with schizoaffective disorder. It is concluded that 1) TTD frequently occurs following cerebral infarct of the MCA territory (60% of the patients in this sample); 2) absence of TTD in the presence of a large cerebral perfusion abnormality may represent neuronal dysfunction of the cerebral cortex; and 3) the presence of TTD without a significant cortical perfusion abnormality may indicate basal ganglia and/or internal capsule infarct. PMID- 2208884 TI - Left ventricular response to exercise in regular runners and controls. A radionuclide evaluation. AB - Radionuclide angiography was performed during upright exercise to compare left ventricular function in nine regular runners to nine age-matched, healthy controls. Heart rate, blood pressure, left ventricular ejection fraction (LVEF), end diastolic volume index (EDVI), end systolic volume index (ESVI), and stroke volume index (SVI) were measured at rest and at 40%, 60%, 80%, and 100% of maximum work capacity (mean maximal workload [KPM +/- SD] was 1,773 +/- 157 in runners and 1,260 +/- 324 in controls). The resting data of runners and controls were similar. There were no significant differences in heart rate, systolic blood pressure, and LVEF between runners and controls during exercise. SVI and EDVI were higher in runners during exercise (P less than 0.05). ESVI was lower in controls at a 60% level of exercise (P less than 0.05). The data indicate that an early and sustained increase in the diastolic volume of the left ventricle is important for enhanced cardiac performance of regular runners during exercise. PMID- 2208886 TI - Migratory multiple bone involvement in a patient with systemic mastocytosis. AB - A young patient with severe generalized osteopenia and multiple compressed vertebral fractures caused by systemic mastocytosis is presented. Extensive clinical, laboratory, and pathologic examination showed the involvement of the skeleton alone. Follow-up bone scintigraphy with Tc-99m MDP during a period of 6 years demonstrated migratory multiple axial lesions. These results suggest that Tc-99m MDP imaging is an accurate detection of the activity of the disease. PMID- 2208885 TI - Cardiac sarcoidosis demonstrated by Tl-201 and Ga-67 SPECT imaging. AB - Ga-67 and Tl-201 SPECT was performed to evaluate cardiac sarcoidosis in a 15-year old boy. Tl-201 SPECT imaging showed decreased uptake in the inferior to lateral wall and Ga-67 accumulation in the area of decreased Tl-201 uptake. These findings suggested cardiac sarcoidosis, and cardiac biopsy confirmed this diagnosis. After corticosteroid therapy, myocardial uptake of Ga-67 disappeared and myocardial TI-201 uptake became more homogeneous. PMID- 2208887 TI - The "warm" sacroiliac joint. A finding in pelvic abscess. AB - Two patients with pain referable to the low back and sacroiliac regions had bone scans with similar findings. In each, one sacroiliac joint was "warm" (uptake on that side was slightly greater than that in the contralateral area). Ga-67 imaging also demonstrated increased uptake in the same locale. Subsequent CT scanning revealed pelvic abscesses adjacent to the affected joints. Asymmetric uptake of bone imaging agent may have been related to hyperemia and "heating" of the sacroiliac joint. Rapid defervescence with antibiotics and drainage (and no CT evidence of bone involvement) suggested that osteomyelitis was not involved in these cases. PMID- 2208888 TI - The hot stripe sign. An unusual variation. AB - Causes of focally increased radiotracer activity on Tc-99m SC liver-spleen scintigraphy include vena caval obstruction, Budd-Chiari syndrome, focal nodular hyperplasia, and tricuspid insufficiency. Artifactually increased activity may result from a malpositioned central venous catheter, free pertechnetate in the stomach, or an overlying breast. An unusual variation of this last artifact, also known as the "hot stripe sign," was encountered during routine liver-spleen imaging of a 65-year-old woman who had breast carcinoma. PMID- 2208889 TI - Myocardial, pulmonary, diaphragmatic, gastric, splenic, and renal uptake of Tc 99m MDP in a patient with persistent, severe hypercalcemia. PMID- 2208890 TI - Malignant lymphoma of the breast detected by gallium-67 scintigraphy. PMID- 2208891 TI - Obstructive uropathy and ectopic ureterocele on renal imaging. PMID- 2208893 TI - Bilateral intraosseous ganglia of the lunates. Bone imaging, CT scanning, and plain film correlation. PMID- 2208892 TI - Incidental skeletal metastases detected by Tc-99m HMPAO leukocyte scanning. PMID- 2208894 TI - Visualization of lumbar spine and sacral area by dynamic renal scan. PMID- 2208895 TI - Localization of gastrointestinal bleeding site with Tc-99m colloid. PMID- 2208896 TI - Inborn 'errors' of drug metabolism. Pharmacokinetic and clinical implications. PMID- 2208897 TI - Clinical pharmacokinetics of mefloquine. AB - Mefloquine, a quinoline-methanol antimalarial, is effective single dose therapy for all species of malaria infecting humans, including multi-drug-resistant Plasmodium falciparum. It is used both in prophylaxis and treatment. Mefloquine is available either as the hydrochloride salt alone, or in a combined preparation with sulfadoxine and pyrimethamine. There is no parenteral formulation. Several assay methodologies have been developed, but high performance liquid chromatography has been the most used in recent pharmacokinetic studies. These have shown in healthy volunteers that mefloquine is absorbed with a half-life of 1 to 4 hours and a time to peak concentration of 7 to 24 hours (median 16.7 hours). Mean peak blood concentrations have ranged between 50 and 110 (median 83) ng/ml/mg/kg. Estimates of total apparent volume of distribution (Vd/f) have ranged from 13.3 to 40.9 (median 19.2) L/kg, systemic clearance (CL/f) from 0.022 to 0.073 L/h/kg (median 0.026 L/h/kg), and terminal elimination half-life from 13.8 to 40.9 days (median 20 days). Systemic clearance appears to be increased in late pregnancy. In uncomplicated falciparum malaria, peak blood concentrations are 2 to 3 times higher than those in healthy subjects ranging from 112 to 209 (median 144) ng/ml/mg/kg because of contraction in the total apparent volume of distribution. Systemic clearance is usually reduced but elimination rates are increased (possibly because of reduced enterohepatic recycling). Mefloquine absorption appears to be reduced in severe falciparum malaria; plasma protein binding exceeds 98% in both healthy subjects and patients. No important drug interactions have been identified as yet, but the potential for serious interactions with quinine has not been adequately investigated. More studies are needed on the disposition of mefloquine in children. PMID- 2208899 TI - Pharmacokinetic drug interactions with cyclosporin (Part I). AB - This article reviews the reported pharmacokinetic interactions between cyclosporin and other drugs. Both rifampicin and the majority of anticonvulsants can decrease cyclosporin concentrations to levels that are at or below the limit of detection for most assays. There have been no reports of any interaction between valproic acid and cyclosporin. Other drugs that have been reported to decrease cyclosporin concentration include sulfadimidine and trimethoprim, nafcillin and octreotide. Erythromycin, ketoconazole and some calcium channel blockers have been clearly shown to increase the concentration of cyclosporin. Other less well documented interactions have been reported with other macrolide antibiotics, other azole antifungal drugs, high dose methylprednisolone, metoclopramide, fluoroquinolones, imipenem/cilastatin, oral contraceptives/danazol, sulindac, methyltestosterone, colchicine, acetazolamide, alcohol and cimetidine. Although the most commonly reported mechanism is inhibition of cyclosporin metabolism, there is increasing evidence that erythromycin, metoclopramide and probably other drugs increase the bioavailability of oral cyclosporin. Two calcium channel blockers which have not been reported to interact with cyclosporin are nifedipine and nitrendipine. With increasing use of cyclosporin, the number of drugs reported to interact will rise. Prudent clinicians should monitor the concentration of this agent more frequently when another drug is added or discontinued and cyclosporin dosage should be adjusted when appropriate. Sustained changes in cyclosporin concentration can result in graft rejection (or graft-versus-host disease) or renal toxicity. Further studies are needed to determine the mechanism of most of these interactions. PMID- 2208900 TI - Comparative study of gentamicin release from normal and low viscosity acrylic bone cement. AB - The pharmacokinetics of gentamicin were studied after total hip joint arthroplasties in 2 groups of 10 patients. The prosthesis was performed in the first group with 'Palacos R plus gentamicin' (normal viscosity), manufactured by Schering, and in the second group with 'Cerafix genta R' (low viscosity) manufactured by Ceraver-Osteal. Both cements included similar concentrations of gentamicin. Urine was collected at 12-hour intervals for 15 days after operation, and drainage fluids for 48, 72 or 108 hours. Blood samples were taken 3 and/or 5 hours after prosthesis implantation. In both cases, high concentrations of gentamicin were found in drainage fluids and urine during the early postoperative period. Mean gentamicin excretion curves were calculated by a computer-aided design program (SIAM) for the 2 cements. The release of gentamicin was biphasic in both cases, although the slow elimination phase appeared to be longer for 'Cerafix'. In the first postoperative period, the drug had a better bioavailability during the rapid elimination phase in the case of 'Palacos'. The calculated peak blood concentration was in the same range for both compounds. The conclusion is drawn that, in patients undergoing total hip joint arthroplasties, gentamicin concentrations reach local levels higher than the minimum inhibitory concentrations of most of the likely sensitive pathogens. However, in both cases, as blood concentrations appear to be low, patients will not be protected against systemic infections. Both cements have similar antibacterial properties but the mechanical properties of 'Cerafix' are the better of the two. PMID- 2208902 TI - Febrile infants less than eight weeks old. Predictors of infection. AB - Febrile infants less than eight weeks old frequently are admitted and receive parenteral antibiotics for treatment of possible sepsis. The authors assess 52 infants less than eight weeks old with a rectal temperature of 38.1 degrees C or higher as having either a readily identifiable focus of infection by physical examination, appearing "toxic" without a focus, or appearing well. The authors screened patients by using white blood cell (WBC) counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and chest radiographs in addition to blood, cerebrospinal fluid and urine cultures. The authors found a 9.6% incidence of bacteria in the 52 infants evaluated, with a 4.3% incidence in those febrile infants who appeared well. Five patients had positive blood cultures with Group B B Hemolytic streptococcus (four patients), and Viridans streptococcus (one patient). A clinical assessment of toxicity and a total band count greater than or equal to 0.5 x 10(3) cells/uL together were sensitive indicators of bacteremia, as were toxicity and a positive CRP. A "toxic" appearance, a WBC count greater than or equal to 15 x 10(3) cells/uL and an ESR greater than 30 were specific indicators of bacteria. Based on these data, identification of bacteremia in febrile infants may be possible with clinical assessment and screening laboratory tests. Because of the relatively small sampling size of this study, the authors feel that evaluation of a larger number of patients is warranted to evaluate these sensitivities in a more diffuse patient population. PMID- 2208901 TI - Wiskott-Aldrich syndrome. A case report. AB - This paper presents a report on a child with Wiskott-Aldrich syndrome. The clinical picture and laboratory findings are characteristic of this disease. The prevailing symptoms have included recurrent respiratory and alimentary tract infections, seborrhic dermatitis-type skin lesions, and thrombocytopenia. Humoral and cellular immunological disturbances have been noted, and the pedigree pattern is very characteristic. PMID- 2208904 TI - Toxic psychosis due to chloroquine--not uncommon in children. AB - Toxic psychosis due to Chloroquine is a relatively uncommon occurrence in childhood. This entity must be kept in differential diagnosis in a case of unexplained psychosis, before resorting to a sophisticated array of detailed investigations. The purpose of this is to familiarize pediatricians with this relatively uncommon entity. The authors encountered four cases of psychosis with a wide variety of symptomatology over a period of the past 18 months. PMID- 2208903 TI - Superficial cultures in neonatal sepsis evaluations. Impact on antibiotic decision making. AB - The authors performed a retrospective analysis of neonatal superficial cultures and their effect on antimicrobial decision making during a nine-month period at Nashville General Hospital. They obtained and reviewed charts of infants (n = 66) having paired superficial (skin and/or gastric aspirate) and deep (blood and cerebrospinal fluid) cultures for the evaluation of early-onset sepsis. Superficial cultures were positive for pathogens (any streptococcus or enteric gram-negative) in 15% (10/66) of cases. Antimicrobial decision making was affected in only one of these cases, and in a seemingly inappropriate manner. In summary, there was no evidence or review that superficial cultures used in sepsis evaluation influenced physician antimicrobial decision making; in one case they may have led to unnecessary antibiotic exposure. PMID- 2208905 TI - Ultrasound guidance. For interventional and intraoperative techniques in infants and children. AB - Since the advent of improved realtime ultrasound (US) imaging and the availability of the needle biopsy attachment, US-guided percutaneous biopsy and the drainage procedure can be performed safely in the pediatric patient. The authors review their experience over 3 years using US-guided interventional techniques in 96 children aged 5 days to 21 years. A wide variety of procedures were performed and included renal biopsy, nephrostomy tube placement, renal mass biopsy, puncture of bladder sinus tract and pancreatic pseudocyst, ventriculoperitoneal shunt placement and intraoperative localization of brain or renal tumor and renal calculi. No complication occurred. US can be safely and accurately used as guide for interventional procedures in children as long as the area of interest can be clearly demonstrated and the depth and necessary angle of needle insertion can be predetermined as feasible. PMID- 2208898 TI - Clinical pharmacokinetics of antibacterial drugs in neonates. AB - Neonatal patients are surviving longer due to the rapid advances in medical knowledge and technology. Our understanding of the developmental physiology of both preterm and full term neonates has also increased. It is now apparent that differences in body composition and organ function significantly affect the pharmacokinetics of antibacterial drugs in neonates, and dosage modifications are required to optimise antimicrobial therapy. The penicillins and cephalosporins are frequently used in neonates. Although ampicillin has replaced benzylpenicillin (penicillin G) for empirical treatment of neonatal sepsis, many of the other penicillins may be used in neonates for the management of various infections. Increased volume of distribution (Vd) and decreased total body clearance (CL) affect the disposition of penicillins and cephalosporins. Decreased renal clearance (CLR) due to decreased glomerular filtration and tubular secretion is responsible for the decreased CL for most of the beta lactams. Aminoglycoside Vd is affected by the increased total body water content and extracellular fluid volume of neonates. The increased Vd, in part, accounts for the extended elimination half-life (t1/2) observed in neonates. Aminoglycoside CL is dependent on renal glomerular filtration which is markedly decreased in neonates, especially those preterm. These drugs appear to be less nephrotoxic and ototoxic in neonates than in older patients, and the role of serum concentration monitoring should be limited to specific neonatal patients. Other antibiotics such as vancomycin, teicoplanin, chloramphenicol, rifampicin, erythromycin, clindamycin, metronidazole and cotrimoxazole (trimethoprim plus sulfamethoxazole) may be used in certain clinical situations. The emergence of staphylococcal resistance to penicillins has increased the need for vancomycin. With the exceptions of vancomycin and chloramphenicol, the efficacy and safety of these other agents in neonates have not been established. The need for serum vancomycin concentration monitoring may be limited, as with aminoglycosides, while safety concerns warrant the routine monitoring of serum chloramphenicol concentrations in neonates. Dosing guidelines are provided, based on the pharmacokinetics of the drugs and previously published recommendations. These dosing guidelines are intended for initial therapy, and close therapeutic monitoring is recommended for maintenance dose requirements to optimise patient outcome. There has been an enormous increase in our knowledge of neonatal physiology and drug disposition. Fortunately, many of the antibacterial drugs used in neonates (e.g. penicillins and cephalosporins) are relatively safe. It will be important to evaluate all newly developed antibiotics in neonates to assure their maximum efficacy and safety. PMID- 2208907 TI - Underlying illness associated with failure to thrive in breastfed infants. AB - Over a four-year period in a suburban pediatric practice, 38 infants aged six months or less were identified with failure to thrive (FTT) while breast-feeding. In seven cases (18.4%), an associated organic illness was diagnosed. Only 2 of 28 breast-fed neonates (8%) were found to have FTT associated with another illness, as compared to 5 of 10 older infants (50%). Breast-fed infants with FTT, particularly those presenting after the first month of life, should be considered high risk for having other disease. Their clinical evaluation should include an appropriate search for organic illnesses. PMID- 2208906 TI - The correlation between low birth weight and learning traits in senior school pupils--a retrospective survey. AB - The purpose of this study was to establish whether a correlation exists between childrens birth weight and their scholastic achievements in high school. This correlation has previously only been investigated only in primary school children and it was felt that it would be interesting to observe whether schooling changed the known status. The records of 718 children were reviewed and there appears to be a statistically significant disability for low birth weight children in the study of exact sciences and foreign languages whilst no significant differences were noted in the humanities and sport. PMID- 2208909 TI - Chondroma in the foramen magnum. PMID- 2208908 TI - Gastrointestinal bleeding in a 15 month old male. A presentation of Munchausen's syndrome by proxy. AB - Munchausen's syndrome by Proxy is a well-described entity that may not always be immediately considered in a complicated case. We describe this syndrome being portrayed through the guise of gastrointestinal bleeding in a 15 month old male and discuss not only the difficulty involved in solidifying this diagnosis but also the consequences that may occur should this diagnosis not be entertained. Failure to diagnose Munchausen's syndrome by proxy often results from failure to consider the diagnosis. These cases frequently have specific characteristics that allow seasoned clinicians to suspect the diagnosis. Once the diagnosis is considered, it is crucial to take steps to protect not only the index patient but also siblings who not infrequently are also recipients of this life threatening form of child abuse. PMID- 2208910 TI - Two siblings with phenotypes mimicking peroxisomal disorders but with discordant biochemical findings. AB - The authors present a report on two sibling with a nearly identical phenotype mimicking peroxisomal disorder but with totally discordant biochemical findings. In an attempt to confirm the diagnosis of a peroxisomal disorder, plasma levels of very long chain fatty acids (VLCFA) and phytanic acid were determined. In addition, fibroblasts profile of VLCFA and plasmalogen levels were evaluated for Case 2. Pathomorphological examinations represented by lymph node and kidney biopsies as well as postmortem examinations of liver, adrenals and brain were performed in Case 1. The phenotypes of both siblings showed marked resemblance to those observed in children with Zellweger syndrome. The results of biochemical tests performed in Case 1, together with abundant peroxisomes in the liver and the wide spectrum of clinical abnormalities suggest pseudo-Zellweger or Zellweger like syndromes, but no conclusive data have been found. The plasmalogen level in fibroblasts as well as the fibroblasts profile of VLCFA noted in Case 2 were within the normal range, thus excluding the possibility of a peroxisomal disorder. The striking phenotype resemblance of the siblings mimicking Zellweger, together with discordant biochemical findings, are difficult to explain on the basis of currently available tests. PMID- 2208911 TI - Diseases that mimic meningitis. PMID- 2208912 TI - Pallid breath-holding spells; evaluation of the autonomic nervous system. PMID- 2208913 TI - [Long-term experience with a PACS subsystem]. AB - Our experiences with a PACS-Subsystem have shown, that it would be more usefull and less expensive, first to install digital archiving systems in single areas. After a certain time of errorfree working the subsstems should be integrated into a superior information system. Fast data networks and userfriendly viewing stations are a basic requirement. Common standards of archiving, independent of the manufacturer, should be considered. PMID- 2208914 TI - [Initial experience with the use of oral gadolinium-DTPA in nuclear magnetic resonance tomography of the pelvis]. AB - The use of an oral contrast medium has so far not become a matter of routine in MR of the abdomen. In the present study the use of orally applied gadolinium-DTPA was examined in respect of tumorous diseases in the minor pelvis. 18 patients with tumours in the minor pelvis were examined before and after oral administration of gadolinium-DTPA (Gd-DTPA). 10 ml/kg body weight of a gadolinium DTPA solution were applied in a concentration of 1.0 mmol/l. T1-weighted and T2 weighted sequences were carried out before application and T1-weighted sequences after application. Oral application gadolinium-DTPA resulted in enhancing the signals of the filled intestinal portions. In 54% of the cases the sequences showed a sharper delineation between tumour and intestine. In 19% the delineation between pathological tissue and intestine on contrast examination was as well defined as in T2-weighted contrast images; in 27% of the cases oral administration of gadolinium-DTPA did not yield any additional information. No significant side effects were seen. PMID- 2208916 TI - [Comparison of computerized tomography and pathologic-anatomic findings of the abdomen in HIV infection]. AB - In a retrospective study the results of abdominal computed tomography (CT) from 48 patients, who died of the complications of HIV infection, were compared with those obtained at autopsy. The CT diagnosis was confirmed at autopsy in 39 cases (81.3%). In nine patients CT results did not correlate with the postmortal findings. This was caused by lack of cooperation, cachexia and the time between the last CT study and the death of the patients. Nevertheless, CT with its standardised imaging planes is an important method for diagnosing and monitoring HIV-related diseases of the abdomen. PMID- 2208915 TI - [Case report: aneurysm of the arteria lusoria--CT and MRI]. AB - CT and MR were used to evaluate a right paramediastinal and retrotracheal mass in a 77-year old woman. An aneurysm of an aberrant right subclavian artery with a lumen partially occluded by parietal clots was clearly diagnosed by both methods. The value of CT and MRI is discussed with regard to planning surgical intervention. PMID- 2208917 TI - [Intra-arterial digital subtraction angiography in diagnosis and course control of an invasive hydatidiform mole]. PMID- 2208918 TI - [Angiographic diagnosis in liver transplantation. I: Evaluation before transplantation]. AB - Our study covers angiographic pretransplant evaluation from 9/88-4/90. 57 out of 73 patients (78%) underwent pretransplant angiography. In all cases aortography, angiographies of the coeliac axis, the superior mesenteric artery, the splenic artery, and portograms were obtained. The arterial studies evaluated the arterial blood supply of the liver, the diameter of the common hepatic artery, aneurysms and a steal effect of the splenic artery. Portography revealed the exact venous collateralisation. Thus angiography remains a valuable procedure for pretransplant evaluation besides ultrasongraphy. PMID- 2208919 TI - Endoscopic ultrasound in oesophageal cancer: the way forward? PMID- 2208920 TI - The role of computerized tomography in the staging of oesophageal cancer. PMID- 2208921 TI - Ultrasound in the diagnosis of abdominal abscesses. PMID- 2208922 TI - The urethra--imaging and intervention in the 1990s. PMID- 2208923 TI - Radiology at the crossroads. PMID- 2208924 TI - Clinical Utility of cranial CT in HIV positive and AIDS patients with neurological disease. AB - An analysis was made of the clinical, pathological and radiological data relating to 117 requests for cranial CT on 83 patients who were HIV positive or had AIDS in one year at St Mary's Hospital. Central to the design was grouping of the patients according to clinical presentation. The aim was to establish whether there was evidence to support the view that, because of their immunocompromised state, these patients may commonly harbour serious, potentially treatable intracranial disease without the usual overt clinical signs. No patient who was only HIV antibody positive had treatable intracranial disease without focal neurological signs. In patients with AIDS, treatable or potentially treatable lesions were mainly confined to those with objective neurological signs or seizures. There is little evidence in this data to support the original hypothesis. While it would be inappropriate to advise that CT should never be carried out in the absence of focal signs or seizures, the results of this study should be useful in ascribing an appropriate degree of urgency to requests for cranial CT in these patients. PMID- 2208925 TI - Bone scintigraphy in nasopharyngeal carcinoma. AB - One hundred and forty-three patients (Group 1) with histologically proven nasopharyngeal-carcinoma (NPC) had bone scintigraphy with 99Tcm methylenediphosphonate (MDP) or dihydroxypropanediphosphonate (DPD) within 2 months of the initial diagnosis. A further 162 patients (Group 2) had bone scans during the course of follow-up if there were symptoms of bone pain or evidence of metastases at other sites. Twenty-three per cent (33/143) of the newly diagnosed NPC patients (Group 1) had evidence of bone metastases. Of these 143 patients, 101 were T0-T2, 16 were T3 and 25 were T4. Thirty-six patients had no neck nodes (NO), 44 were N1, 25 N2 and 38 N3. Of the 162 patients in Group 2, 96 (59%) had a positive bone scan. The commonest sites for bony metastases from NPC were the spine, ribs, pelvis and lower limbs in order of frequency. There is a highly significant association with the nodal stage but no association with the UICC T staging which is not adequate in nasopharyngeal carcinoma. In our part of the world, bone metastases from NPC are a common cause of an abnormal bone scan. PMID- 2208926 TI - Magnetic resonance imaging in aggressive fibromatosis. AB - The magnetic resonance imaging (MRI) features of aggressive fibromatosis in 11 patients (five with recurrent tumour) and its contribution to patient management are described. Tumour signal intensity ranged from being low to isointense with respect to muscle on T1-weighted images while being predominantly of heterogenous increased signal intensity on T2-weighted images. A post-contrast (Gd-DTPA) study demonstrating diffuse tumour enhancement was of value in assessing tumour extent in two patients. CT in six patients and angiography in two patients provided no additional information while tumour relationship to neurovascular structures and extent was better appreciated on MRI. MRI was accurate in predicting resectability in all six patients who had surgery. PMID- 2208927 TI - A double-blind clinical study comparing the safety, tolerance and efficacy of ioversol and iohexol in intravenous urography. AB - A double-blind trial in 80 patients showed no significant difference in the efficacy, tolerance and safety for intravenous urography between the new contrast medium Ioversol (Optiray Mallinckrodt Inc.) and the well established medium Iohexol (Omnipaque, Nycomed [UK] Ltd). Minor transient rises in AST/ALT were noted in approximately 10% of each group which were regarded as clinically insignificant. Both media were well tolerated with no significant side-effects. PMID- 2208928 TI - Left coronary angiography in the pre-operative diagnosis of thrombosis of the left atrium or its appendage in rheumatic mitral stenosis. AB - We studied the utility of pre-operative selective left coronary angiograms for detecting thrombosis in the left atrium or its appendage in 81 patients with rheumatic mitral stenosis, who subsequently underwent open-heart surgery. Thrombus was predicted by the angiographic demonstration of neovascularity seen as a bunch of small vessels arising from the circumflex branch of the left coronary artery coursing superiorly to the region of the left atrial appendage and terminating in a network of smaller vascular channels with a blush of contrast medium coalescing into small 'lakes'. This pooling of contrast medium was considered essential for positive angiographic diagnosis. Based on these criteria, the angiographic diagnosis of thrombus was made in 27 patients. Thrombus was found in 33 patients at surgery. Selective left coronary angiography had a sensitivity of 72.7%, specificity of 92.7% and predictive value of 88.8% for detecting thrombi in the left atrium or its appendage. Coronary angiography should be performed in all the patients with mitral stenosis who are undergoing cardiac catheterization especially if balloon mitral valvoplasty or closed mitral valvotomy are planned. PMID- 2208929 TI - Enhancement of collapsed lung: a potential pitfall in CT interpretation. AB - In the presence of a pleural effusion there may be compression of adjacent lung causing segmental atelectasis. In some effusions minor degrees of atelectasis give rise to a fine rim of enhancing lung on computerized tomographic (CT) examination which should not be misinterpreted as extravasated contrast from aortic or oesophageal lumen. PMID- 2208931 TI - Indium labelled leucocyte scintigraphy in occult infection: a comparison with ultrasound and computed tomography. AB - A review of five year's experience of the use of 111Indium labelled leucocyte scintigraphy (111In WBC) in the investigation of suspected sepsis is presented. The results of 257 111In WBC scans for which a definitive diagnosis was subsequently established were available for analysis. The findings are compared with those of ultrasound (130 cases) and computed tomography (82 cases) and the final clinical outcome. The sensitivity and specificity of the 111In WBC for the series were 97% and 91% respectively. The major cause of the false positive 111In WBC results was activity within the bowel not due to infection. Thrombus within the inferior vena cava caused a false positive 111In WBC result: this is previously undescribed. There were a large number of incorrect ultrasound results, particularly with abdominal and pelvic abscesses, pyelonephritis, peritonitis and non-infected fluid collections, showing that a negative ultrasound cannot exclude infection. The relative merits of the three modalities are discussed, emphasizing that more than one technique may be required to establish a diagnosis. PMID- 2208930 TI - Imaging inflammation with 99Tcm HMPAO labelled leucocytes. AB - Labelling leucocytes with 99Tcm using hexamethylpropyleneamine oxime (HMPAO) utilizes the advantages of technetium over indium in imaging inflammation. A retrospective study has been performed on 43 consecutive patients imaged with 99Tcm HMPAO labelled leucocytes in order to assess the reliability of the technique. Particular attention was paid to the different handling characteristics of the 99Tcm HMPAO labelled cells compared with those labelled with indium. It was found that 99Tcm HMPAO labelled leucocytes gave an overall accuracy of 93.2%, a sensitivity of 92.8%, a specificity of 93.3% and a positive predictive value of 86%. 99Tcm HMPAO labelled leucocyte scanning provides a reliable method of imaging inflammation, though errors in interpretation may occur due to the hepato-biliary excretion of activity that occurs with this technique. PMID- 2208932 TI - Portal hypertension secondary to sigmoid colon arteriovenous malformation. AB - A case of portal hypertension secondary to an arteriovenous malformation of the sigmoid colon is presented. The importance of mesenteric angiography in the diagnosis of this condition is discussed. The dramatic clinical improvement in this case following surgery emphasizes that arteriovenous malformations of the gastrointestinal tract represent a potentially curable cause of portal hypertension. PMID- 2208934 TI - CT and MRI findings in paraoesophageal omental herniation. AB - CT and MRI findings in a patient with retrocardiac paraoesophageal omental herniation are presented and the literature reviewed. Characteristic CT features included a bilobed, retrocardiac fatty mass, with branching blood vessels throughout, a midline septum and extension through the diaphragm. MRI confirmed the fatty nature of the bilobed, intrathoracic mass and clearly defined pedicles of fat, from each lobe, extending into the abdomen through the oesophageal hiatus of the diaphragm. PMID- 2208933 TI - Mediastinal lipoblastoma of infancy. AB - We report the case of a rapidly expanding mediastinal and chest wall lipoblastoma in an 11-month old infant. Clinical presentation was respiratory distress and chest radiographs revealed a large soft tissue mass in the anterior mediastinum without specific features. CT scanning demonstrated a mass of principally fat attenuation, with enhancing hyperdense soft tissue whorls, which had a compressive effect on normal intrathoracic structures. At surgery the tumour was removed without complication and histology demonstrated an encapsulated, well differentiated lipoblastoma. PMID- 2208935 TI - Ureterocaecal anastomotic tumour diagnosed by sinography. AB - The development of adenoma and adenocarcinoma at the site of ureterocolic anastomosis are recognized complications of internal urinary diversions, most of which are to the sigmoid colon. A rare case of adenoma developing at a ureterocaecal anastomosis was diagnosed by the unusual means of percutaneous trans ureteric sinography. PMID- 2208936 TI - Nalbuphine hydrochloride (Nubain, DuPont) as premedication for radiological procedures. AB - Nalbuphine hydrochloride, a semi-synthetic agonist antagonist opioid, has been used in an intravenous injection of 20 mg followed by Diazemuls not less than five minutes later as a premedication in 462 patients undergoing a range of radiological procedures over a 2 year period. In all but two patients excellent sedation was obtained and there were no episodes of respiratory depression nor cardiovascular disturbances. PMID- 2208937 TI - Evacuation proctography (defecography). A new seat and method of examination. AB - A new evacuation proctography (defecography) seat and method of examination is described. The seat was constructed in association with the department of biotechnology. It is constructed of perspex and radiographic demonstration of the distal rectum and anal canal region is obtained without distracting artefacts. PMID- 2208938 TI - Imaging the testis and scrotal structures. PMID- 2208939 TI - Ultrasound appearances of De Quervain's thyroiditis. PMID- 2208940 TI - Improving accident and emergency radiology. PMID- 2208942 TI - 1990 Colorado Medical Society Physician's Directory. PMID- 2208941 TI - Embolization vs. embolisation and embolize vs. embolise? PMID- 2208943 TI - A retrospective study of apparent and relative polycythaemia: associated factors and early outcome. AB - Thirty four consecutive patients (31 male, 3 female) with raised PCV (males greater than 0.51, females greater than 0.47) and normal red cell mass (apparent polycythaemia) and with normal red cell mass but a low plasma volume (relative polycythaemia) were studied retrospectively. Male sex, smoking, hypertension and diuretic therapy were found to be associated factors while obesity and excessive alcohol consumption were less clearly linked. Only three patients (all males) were negative for all these factors. Approximately 15% of patients had arterial hypoxaemia. There was no difference in the incidence of these factors in the two sub-groups. Possible mechanisms relating these factors to the raised PCV are discussed. Preliminary follow-up data show that in approximately one third of the patients the PCV returns to normal and that this is most likely in those patients with a normal recumbent PCV (at the time of the blood volume study). In one third the PCV continues to be raised, and the remainder have only intermittently raised PCV. As a result of this study, prospective studies of the incidence of hypoxaemia in these patients and of the PCV outcome with and without correction of associated factors are planned. PMID- 2208944 TI - Thrombocytosis in Henoch-Schonlein syndrome. AB - To ascertain the frequency of thrombocytosis in Henoch-Schonlein syndrome (HSS) a small retrospective survey was undertaken. Sixty-five per cent of the cases of HSS showed thrombocytosis, which might be related to the severity of the illness. PMID- 2208945 TI - Guidelines for the clinical use of blood cell separators. The Clinical Haematology Task Force of the British Committee for Standards in Haematology. PMID- 2208946 TI - Alcohol-associated haemolysis in Zieve's syndrome: a clinical and laboratory study of five cases. AB - In 1958 Zieve described a syndrome of jaundice, hyperlipidaemia, and transient haemolytic anaemia associated with alcohol abuse. The clinical and laboratory features of five cases are reviewed. All patients presented with acute abdominal pain and fever. Four had a history of a recent alcohol binge. Hyperlipidaemia was present in two patients; this subsided before the onset of haemolysis. The red cells showed features of an acquired pyruvate kinase deficiency: an increased autohaemolysis with only partial correction with glucose, low red cell ATP, and instability of pyruvate kinase when haemolysate was heated to 55 degrees C. These changes were not observed in a control group of chronic alcoholics without haemolysis. PMID- 2208947 TI - Alpha-thalassaemia and beta-thalassaemia traits: biological difference based on red cell indices and zinc protoporphyrin. AB - alpha-thalassaemia and beta-thalassaemia traits are two commonly encountered haemoglobinopathies in South East Asia. Both present with hypochromia and microcytosis. The use of modern electronic or optical cell counters which measure accurately the red cell parameters has allowed for an initial quick screening for the presence of thalassaemia. Seven red cell parameters were measured by the Technicon H1 cell analyser--red cell count, Hb, MCV, MCH, red cell distribution width (RDW) and haemoglobin distribution width (HDW). Discriminant analysis of these parameters and zinc protoprophyin (ZP) indicates that in healthy individuals, alpha-thalassaemia can be differentiated from beta-thalassaemia with an accuracy of 86% when analysed as a group. In hospitalized patients the accuracy dropped to 71% due to biases of concomitant illness. The two most important parameters for indicating differences between alpha- and beta thalassaemia are MCV and ZP. The results confirm further that though alpha- and beta-thalassaemia have the same phenotypic expression they differ in their biology. PMID- 2208948 TI - Acute effects of 3'-azido-3'-deoxythymidine on the cell cycle of HL60 cells. AB - The average doubling times of HL60 cells grown in the presence of 0,5,10 and 100 microM 3'-azido-3'-deoxythymidine (AZT) for 72 h were, respectively, 51.1, 65.7, 69.0 and 76.3 h. This drug-concentration-dependent prolongation of the cell doubling time was associated with a progressive increase in modal cell volume. The technique of combined Feulgen microspectrophotometry and 3H-thymidine autoradiography revealed that the cell cycle distribution of HL60 cells cultured in the presence of 5 and 100 microM AZT for 48 h was abnormal, with an increased percentage of cells in the S phase and a decreased percentage in the G1phase. From the cell doubling times and the cell cycle distribution data, and making a number of assumptions, upper limit estimates for the duration of the S phase in cultures containing 0,5 and 100 microM AZT were calculated to be 26.2, 35.8 and 49.6 h, respectively. The data indicate that concentrations of AZT achieved in the plasma of patients receiving this drug (i.e. 5 microM) cause a substantial prolongation of both the cell cycle time and the duration of the S phase of HL60 cells. It therefore seems likely that some of the toxic effects of AZT seen in vivo, including impairment of bone marrow function, are at least partly related to AZT-induced disturbances of DNA synthesis and proliferation in human cells. PMID- 2208949 TI - A survey of platelet serology in UK laboratories (1987): an assessment of the efficacy of using chloroquine-treated platelets to distinguish between platelet specific and anti-HLA antibodies. The UK Platelet and Granulocyte Serology Working Group. AB - This survey was designed to determine the ability of participants to distinguish between platelet specific and anti-HLA antibodies. Four well characterized reference reagents and 10 unknown samples were sent to 29 laboratories affiliated to the UK Platelet and Granulocyte Serology Working Group and to three overseas reference laboratories. Results were obtained from 27 Working Group laboratories and from 2 reference laboratories. Overall, the results indicate that the use of chloroquine-treated platelets alone, without an independent test for anti-HLA antibodies, was insufficiently reliable to elucidate mixtures of platelet specific and anti-HLA antibodies. Laboratories using chloroquine-treated platelets were no more successful in elucidating the antibody composition of sera containing platelet-specific and anti-HLA antibodies than those laboratories which did not use this technique. The results may indicate a lack of experience with the chloroquine technique and suggest that further studies into the performance of the technique are required. The survey also provided insights into other areas of platelet serology: (1) There was a decrease in the incidence of false-positive results compared to earlier UK surveys. [2) All laboratories detected potent platelet-specific antibodies but weakly reactive antibodies were less readily detected. (3) Laboratories using fluorescent antiglobulin techniques recorded fewer errors than laboratories using ELISA techniques. (4) Laboratories using paraformaldehyde (PFA)-treated platelets in fluorescent antiglobulin techniques did not perform better than laboratories using untreated platelets. PMID- 2208950 TI - Guidelines on hospital blood bank documentation and procedures. British Committee for Standards in Haematology, Blood Transfusion Task Force. PMID- 2208952 TI - Transfusion reaction due to Anti-Fya in donor blood. PMID- 2208951 TI - A bite by a carpet viper (Echis carinatus) in a research institute. PMID- 2208953 TI - Tests of thyroid function: update in the diagnosis and management of thyroid disease. AB - Current thyroid function tests give the clinician powerful tools for the accurate assessment of thyroid status in the majority of patients encountered. There are, however, a small number of clinical situations in which there appear to be inconsistencies in the interrelationship of the thyroid function tests and/or in which they are apparently inappropriate to the clinical status of the patient. In most instances, there is a rational explanation for these observed alterations. The application of this information should allow clinicians to further refine their diagnostic accuracy and thereby enable them to proceed with an appropriate therapeutic or management program. PMID- 2208954 TI - Management of primary hypothyroidism. AB - Primary hypothyroidism is a common condition requiring lifelong treatment and monitoring. The type and amount of thyroid hormone replacement, selection of laboratory tests, and timing of office visits are all important for optimizing patient well-being and reducing the costs of medical care. The aim of treatment is to bring the patient to the euthyroid state. Currently this is defined as a normal serum concentration of TSH by recently developed sensitive and specific immunometric assays, and is accomplished by titrating the dose of levothyroxine and changing it not more often than at 4- to 6-week intervals. As an indicator of euthyroidism, the sensitive TSH assay has advantages over tests of serum T4, FT4I, T3, FT4, and TSH by RIA because it is independent of TBG changes that result from pregnancy, birth-control pills, and estrogen replacement, is not spuriously elevated by the levothyroxine treatment itself, and is the only test that detects both subclinical hypothyroidism and subclinical hyperthyroidism. Additional serum tests are not usually necessary but have advantages under special circumstances. Once the optimal replacement dose is determined, monitoring can be done yearly or even bi-yearly, depending on the adequacy of patient education and patient compliance. PMID- 2208955 TI - Diagnosis of thyroid dysfunction in ambulatory patients: primacy of the supersensitive thyroid-stimulating hormone assay. PMID- 2208956 TI - Correlation between glycemia and glycated hemoglobin. PMID- 2208957 TI - Advances in the diagnosis and pathogenesis of diabetes mellitus and its complications. PMID- 2208958 TI - Modern management of the insulin-requiring patient. PMID- 2208959 TI - Update: non-insulin-dependent diabetes mellitus. PMID- 2208960 TI - Adolescent endocrinology. PMID- 2208961 TI - Patient assessment and treatment planning in child and adolescent partial hospital programs. AB - Thirty-six patient records were examined during site visits to 18 child and adolescent (PH) programs. The documentation of patient assessment and treatment planning was examined. The history of present illness, past psychiatric history, and medical history were at least adequate in about 60-70% of evaluations. Treatment plans were generally complete, but at least one-half of mandated treatment plan reviews lacked revisions. Psychiatric justification of admission and diagnosis was poor in 41% and 44% of charts, respectively, and there was no documentation of ongoing psychiatrist-patient contact in 44% of charts. Possible explanations for these findings include inadequate funding of PH programs, lack of psychiatric time, and uniform approaches to treatment. PMID- 2208962 TI - Rural community mental health consumer satisfaction and psychiatric symptoms. AB - This study examined the impact of therapy on psychiatric symptoms and consumer satisfaction in a rural community mental health center. Utilizing the Brief Symptom Inventory (BSI) and an evaluation of service questionnaire (EOS), designed by the authors, results indicated positive outcomes for both measures (88 subjects). Small but significant correlations were obtained for the BSI and EOS (r's .29 to .59). Implications for future research and treatment are discussed focusing on time of intervention and symptom quality. PMID- 2208963 TI - Strategies for overcoming barriers to community-based housing for the chronically mentally ill. AB - This paper reports the results of a study of community acceptance of housing for the mentally ill in Maryland. The findings indicate that community opposition is less likely to occur (1) when establishing apartmental living arrangements rather than group homes, (2) in less organized neighborhoods, (3) where other housing for specialized populations has not been previously developed, and (4) by using a "low profile" strategy which avoids informing community members in advance of start-up. PMID- 2208964 TI - The longitudinal use of the Global Assessment Scale in multiple-rater situations. AB - The Global Assessment Scale was used by multiple clinicians to rate 108 chronically mentally ill outpatients for 18 months. With prior training, high interrater reliability was obtained. Analysis suggests that fluctuations in patients' scores were not attributable to measurement error due to the sequential ratings of multiple clinicians. Moreover, GAS means were inversely correlated with decompensations over the study period. Results indicate that the DMS-III-R recommended use of the GAS in multiple-rater outpatient facilities can be both reliable and clinically useful when supported by thorough staff training. PMID- 2208965 TI - Dropout from intake, diagnostics, and treatment. AB - Characteristics of 321 children, their families, the clinical process they encountered, and their service usage were tested for relationships with dropout from intake, diagnostics, and treatment at a child guidance clinic. The results indicate clinicians need to be attentive to whom they interview in the intake phase, whom cases are assigned to, the duration of the diagnostic and treatment phases, and the length of time clients have to wait on waiting lists for services. These findings indicate the methods used for providing services to clients are the best predictors of dropout. PMID- 2208966 TI - The chronically mentally ill group treatment for individuals with schizophrenia. AB - Comprehensive treatment programs for individuals with schizophrenia usually include a variety of groups, many of which have concrete tasks as a focus: medication management, social skills training, meal preparation, etc. These groups can simultaneously serve more general rehabilitative purposes if leaders apply principles of group leadership which recognize the neuropathological substrate of schizophrenia and which take into account the specific interpersonal characteristics and needs of individuals who have the illness. This paper presents a framework for leading task-oriented groups for individuals with schizophrenia and give examples from a medication group in a psychosocial rehabilitation program. PMID- 2208967 TI - Providing medical care to mentally ill women in the community. AB - Medical care is difficult to provide for chronic psychiatric patients in the community, but is easier to provide if it is integrated into a larger program of services. A comprehensive care model for this group should take into account the need for rehabilitation, social services, medication, crisis care, physical medical care and overall continuity. This article describes a multi-service program in Toronto operated by the "Friends of Shopping Bag Ladies," and the provision of medical care to the participants of this program by visiting general practitioners. PMID- 2208968 TI - Recent data on the epidemiology and prophylaxis of human rabies in France. AB - Rabies is an animal disease which is transmitted to man only by accident, most often through the bite (more rarely after scratches or licks of mucosa) of a rabid animal, domestic or wild. A good knowledge of the epizootiology of animal rabies is therefore necessary to establish, on solid grounds, the prophylaxis of human rabies. Inter-human transmission of rabies being an exceptional event which will be considered separately, the epidemiology of human rabies mainly studies the sources and circumstances of human exposure to rabid animals, which differ according to the epizootiology of animal rabies in a given country: either enzootic (or hyperenzootic) canine rabies, or enzootic selvatic rabies. It appears that the risk of human rabies is higher in the first situation for two reasons: (i) rabies viruses show an increased virulence due to numerous serial passages in dogs (viruses with short incubation period) and (ii) high frequency of dog-man contacts due to the high density of both populations. PMID- 2208969 TI - Yersiniosis. PMID- 2208970 TI - The interaction of Brucella melitensis 16-M and caprine polymorphonuclear leukocytes. AB - In the present work, a study about the phagocytosis and intracellular killing of the polymorphonuclear leukocytes (PNMLs) of goat in animals clinically healthy, vaccinated and inoculated experimentally with Brucella melitensis has been done. During 6 weeks postvaccination and postinfection, the evolution in these animals has been studied. Although animals were inoculated or vaccinated, there was influence in the phagocytosis and intracellular killing phases, even though a very low indices in this last phase, and in every event were given. The nitroblue tetrazolium (NBT) reduction indices in PMNLs were also investigated with different fractions of B. melitensis. Very low indices were given, and no influence of a postvaccination or postinfection state was found. Finally, the serum bactericidal action in every animal was studied with Brucella melitensis and this effect was not found. PMID- 2208971 TI - Macrophage lysozyme stimulation by fructose-1-6-diphosphate. AB - FDP produces an increase of serum lysozyme concentration which may be related to stimulation of the phagocytic activity. Mice macrophages in vitro produce extracellular and intracellular LSZ (lysozyme) and FDP (fructose-1-6-diphosphate) increases this production. Also in vivo FDP stimulates the macrophages intracellular lysozyme production. The toxic activity in vitro and the protection in vivo against Staphylococcus pyogenes after FDP administration can also be related to macrophage stimulation. PMID- 2208972 TI - Immunomodulatory properties of a strain of Mycobacterium chelonae--II. Qualitative and quantitative stimulation of mouse splenocytes by Mycobacterium chelonae. AB - Intraperitoneal [i.p.] and subcutaneous [s.c.] administration to BALB/C mice with a single dose of 5 mg/kg body weight (wet weight) of live Mycobacterium chelonae (Mch) augmented splenocyte blastogenesis. Similar increases in splenocyte blastogenesis manifested during a single oral administration to mice with 100 mg/kg body weight (wet weight) of this Mycobacterium. When splenocytes issued from these mice are activated by mitogens, a highly significant enhancement of lymphoblastic transformation was observed. On the other hand, multiple oral administrations with 50 mg/kg body weight (wet weight) to Mch/dose did not manifest statistically significant differences in splenocyte blastogenesis as compared to controls. Meanwhile, a highly increased transformation of splenocytes, issued from such mice, is observed in response to lectins and to the mitogenic effect of this microorganism. Splenocyte counts have shown 44.5, 37.6, and 23.2% increases in response to i.p., s.c. and multiple oral administration of this bacterium, respectively, as compared to solvent controls. Repeated s.c. administration of this mycobacterium manifested short lived and weak syndromes of anaphylactic shock during and immediately after the second inoculation of Mch. This phenomenon is not observed during repeated intraperitoneal and oral administrations. In conclusion, parenteral (i.p. and s.c.) and oral administration of Mch stimulates the immune system of mice. This effect is characterised by increased in vivo cell multiplication and by enhanced ex vivo DNA synthesis of murine splenocytes. The need of further studies is eminent to elucidate classes of immunocompetent cells involved in this phenomenon. PMID- 2208973 TI - Yellow fever haemagglutination-inhibiting, neutralising and IgM antibodies in vaccinated and unvaccinated residents of Ibadan, Nigeria. AB - A survey for yellow fever virus haemagglutination inhibiting (HI) and neutralising (N) and IgM antibodies was carried out in unvaccinated people in Ibadan and in those immunised with the yellow fever 17-D vaccine. A total of 207 people were tested for HI antibody to yellow fever and two other flaviviruses namely: Wesselsbron and Uganda S. viruses. Prevalence of HI antibody to each flavivirus antigen was as follows: Yellow fever 26%, Wesselsbron 18% and Uganda S 33%. Of the 207 people, 37 (18%) had yellow fever N antibody. There was a higher prevalence of N antibody to yellow fever virus in adults than children. Twenty one people vaccinated with 17-D yellow fever vaccine donated post-vaccination sera; 10 (48%) had no prevaccination HI antibody, 7 (33%) had HI antibody to one flavivirus and 4 (19%) to two or more flaviviruses. Ninety percent of seronegative people and all those with prevaccination flavivirus antibodies developed HI or N antibody, following vaccination. A total of 58 unvaccinated people were tested for yellow fever IgM antibody by an enzyme linked immunosorbent assay, 2 (3%) were positive; suggesting that active yellow fever transmission was in progress at the time of survey. PMID- 2208974 TI - Factors enhancing and inhibiting the development of primary medical care in community health centres. AB - This study examined factors inhibiting and enhancing the development of primary medical care within community health centres. Nine centres with medical services, representing a range of financial administrative arrangements and a spread of locations, were selected for investigation. A modified version of the Community Health Accreditation and Standards Project (CHASP) review process was developed to look at areas of health service functioning. Effective internal management and a shared ethos were the strongest predictors of favourable outcomes overall. Salaried, as opposed to fee-for-service, financial arrangements led to better outcomes in most function areas, although salaried arrangements in themselves were not sufficient to produce good outcomes. All centres that performed well had community management structures, but the presence of such structures did not always guarantee good outcomes. The educational background and experience of the doctors had no effect. The study confirmed that primary medical care within community health centres represents a viable, alternative model of general practice in Australia and identified some factors that could strengthen it further. PMID- 2208975 TI - Counting heads: estimating traumatic brain injury in New South Wales. AB - The public health problem of head injuries contributes to considerable morbidity in the community and is the commonest cause of death in young adult Australians. However, estimating the incidence of head injury has been difficult, and has varied between countries and over time. This paper critically appraises the methodological issues contributing to head injury/brain injury incidence estimates, in particular case definition, differing data sources, and methods of case ascertainment. The most appropriate definition from a methodological service provider perspective is one which clearly distinguishes between potential and actual brain injury. The results from a study which used the most accurate methods have been extrapolated to NSW, and reduce the estimated brain injury incidence in NSW from a reported 392 to 180 per 100,000 incident cases per year. This revised estimate implies that in 1990 there will be about 10,500 new cases of traumatic brain injury, of which an estimated 400 will result in serious physical or mental disability. These estimates were originally calculated to enable the development of an appropriate level of health service provision for brain-injured persons through the NSW Brain Injury Program. PMID- 2208977 TI - Is probability sampling always better? A comparison of results from a quota and a probability sample survey. AB - Two surveys in the same defined population in Sydney's western suburbs in 1986 and 1987 provided the opportunity to compare results obtained from a quota and a probability sample survey. These surveys were designed to provide information for the planning of local health promotion programs. The quota sample survey was conducted in shopping centres and used quota sampling to select 1727 respondents. In the second survey, area probability sampling was used to select 484 respondents. This survey had a response rate of 65 per cent. There were 15 questions common to both surveys; results of only three differed significantly (p less than 0.05) between surveys. None of these differences was important from a public health perspective. The agreement between the results of these two surveys probably reflects the fact that the same selection bias has operated in both. Unless a very high response rate can be achieved, quota sample surveys with age and sex quota controls may be an acceptable alternative to probability sample surveys for gathering local data relevant to the development of health programs. PMID- 2208976 TI - Reminder letters for women when repeat Pap smears are due. AB - Regular participation in a high-quality screening program by all 'at risk' women is necessary if Australia is to be maximally successful in preventing cervical cancer. This paper discusses the use of reminder letters as one method of facilitating participation. Options for the source of the letters are discussed. It is concluded that basing the recall letters on a register of previously screened women is the only feasible approach within the Australian health care system. The impact of reminder letters on achieving regular participation by Australian women remains to be tested. PMID- 2208978 TI - The role of community educators in achieving Australian health goals: a public health approach to weight control on the North Coast, NSW. AB - This paper describes the recruitment, training and supervision of Community Educators for weight-control programs, reports the results they have achieved to date, and offers suggestions for improving similar programs. This material is discussed in relation to suggestions about nutrition published by the Better Health Commission. PMID- 2208979 TI - Television food advertising: a challenge for the new public health in Australia. PMID- 2208980 TI - Nutrition and public health: division of labour in the study of nutrition. AB - This article draws inferences from changes in the style of a nutrition journal which was originally published by the Commonwealth Department of Health, and is now published by the Australian Dietitians' Association. The changes reflect developments in the field of nutrition, towards more 'scientific' styles of inquiry and publishing, against the backdrop of a division of labour in which (mainly male) laboratory scientists produced scientific knowledge which was then communicated by (mainly female) dietitians and nutritionists. Consistent with the approach of the 'new public health', this paper argues that reliance upon 'scientific' methods alone diverts attention from the social, economic and political conditions which help explain not only the improvements earlier in the century, but current difficulties in bringing about further improvements. PMID- 2208981 TI - A critical review of Australian cancer organizations' public education material. AB - Because of the potential benefits of primary prevention and early detection of cancer, a considerable proportion of the efforts of State cancer organizations has been directed towards public educational programs. The study aimed to determine the level of agreement in the messages contained in the written educational material of the State and Territory cancer organizations in Australia. Pamphlets and brochures dealing with primary and secondary prevention of breast, cervical, skin and bowel cancers were obtained. The materials were compared on a number of dimensions: the characteristics of people who are at increased risk of contracting the cancer, how to avoid the cancer through primary prevention, how and when to screen in the case of secondary prevention, and action to be taken if a sign or symptom indicative of cancer is discovered. The study found a lack of agreement in the messages of the State cancer organizations. Some hypotheses are suggested to explain the discrepancies. In addition, some suggestions for remedying this situation are provided. PMID- 2208982 TI - Social factors associated with the decision to relinquish a baby for adoption. AB - Little is known about the characteristics, social circumstances and mental health of women who give a child up for adoption. This paper reports data from a longitudinal study of 8556 women interviewed initially at their first obstetrical visit. In total, 7668 proceeded to give birth to a live singleton baby, of which 64 then relinquished the baby for adoption. Relinquishing mothers were predominantly 18 years of age or younger, in the lowest family income group, single, having an unplanned and/or unwanted baby and reported that they were not living with a partner. These women were somewhat more likely to manifest symptoms of anxiety and depression both prior, and subsequent to, the adoption, but the majority of relinquishing mothers were of 'normal' mental health. The decision to relinquish a baby appears to be a consequence of an unwanted pregnancy experienced by an economically deprived single mother rather than the result of emotional or psychological/psychiatric considerations. These findings document a particular dimension of the impact of poverty on health. PMID- 2208984 TI - Hierarchies, bureaucracies and professions. The Medicare Review. Part two. AB - This paper is both a personal account and an analysis of the Medicare Review (part 2) that took place in 1985-6, to which I acted as Consultant Adviser. It analyses health policy issues associated with the recent inquiry to consider expanding the Medicare Scheme to include the services of some paramedical occupations. It considers what took place, the history of events leading up to the Review, the complexities of the review process and issues of implementation as well as the wider context. The paper moves from the descriptive to the analytical level to explain and interpret the review process from both a sociological and social policy point of view. The relevance of the Review to public health is twofold: the development and application of a new methodology to evaluate complementary health modalities on one hand, and the role of the Review in promoting both the legitimacy of these occupations, and, from a public policy analysis viewpoint, cost containment, on the other. PMID- 2208983 TI - Purposely self-inflicted injury resulting in death and hospitalisation in New Zealand. AB - Purposely self-inflicted injury is the second most common cause of injury death in New Zealand and is also a major cause of hospitalisation. Despite the significance of the problem there has been relatively little research undertaken in New Zealand. Injury mortality and morbidity data files for 1984 were examined and upgraded to provide as comprehensive an overview of this injury problem as the data would permit. The results show that the fatality rate was highest amongst the elderly, and males had higher death rates than females for all ages. In contrast to this, hospitalisation rates peaked among the 15-20 year olds and females had higher rates than males for all ages. Whereas Maori had a significantly lower fatality rate than non-Maori the converse was the case for hospitalisation. A more consistent effect occurred for marital status, the married group had significantly lower fatality and hospitalisation rates than the non-married group. The major occupational group "production, transport and labourers" had the highest mortality rate, whereas service workers, in particular house staff, had the highest rate of morbidity. Whereas hanging was the most common method (33%) used in fatal injury events, poisoning was the most common method (91%) used for those events which resulted in hospitalisation. In the latter case, psychotropic agents, in particular tranquillisers, accounted for 50 per cent of all poisoning. These data show that mortality experience is not a reliable guide to injury morbidity experience. Prevention is discussed in the context of limiting the availability and lethality of agents. PMID- 2208985 TI - Quantification of the fetal electrocardiogram using averaging technique. AB - A signal analysis procedure is described for obtaining time intervals parameters of the fetal electrocardiogram as recorded from the maternal abdomen. Applying averaging to the fetal electrocardiogram quantification of the PR interval, QRS duration and QT interval were measured. This technique which includes the subtraction of an averaged maternal ECG waveform using cross-correlation function and fast Fourier transform algorithm, enables the detection of all the fetal QRS complexes in spite of their coincidence with the maternal ECGs. Results that were obtained from 21 pregnant women at the gestational age of 32-41 weeks and an example of a recording with fetal premature ventricular contractions are presented. This method shows an important improvement with respect to detection of fetal heart rate and detection of arrhythmia disturbances in the fetal ECG. The averaging procedure can be used to evaluate long-lived alterations in the fetal ECG. PMID- 2208987 TI - A QuickBasic computer model of spermatogenesis. AB - A program in QuickBasic has been written for the purpose of simulating spermatogenesis in any animal in order to more fully understand the dynamics of sperm production. Two basic informations are needed to run the program: controlling factors (CF-s) and the stem cell population size. These can be interactively manipulated for theoretical evaluations or be implemented from actual animal data for assessment of valid sperm yield. PMID- 2208986 TI - A numerical approach to activated sludge kinetics. AB - Mass balance equations for biomass and substrate are numerically solved to determine the effects of different variables on suspended growth systems. Dimensionless quantities and computer techniques are used to express the results generally. Monod kinetics and reactors-in-series principles are applied to explain variations in axial dispersion and waste-water quality experienced in real systems. An attempt has been made to determine the effluent concentrations as a function of two parameters, i.e. a dimensionless time and a dimensionless substrate concentration (of the incoming waste-water). The computer results have been generalized in the form of design tables. An available approximate method for plug-flow reactors has been compared with the solution obtained in this way, and the resulting error has been demonstrated. In this study, results obtained from large numbers of reactors-in-series are reported to characterize plug-flow conditions. Performance of reactors subjected to varying degrees of axial dispersion will be stressed in a subsequent paper. PMID- 2208988 TI - Utilization of a computer-controlled laboratory workstation (Biomek 1000) in routine radioimmunoassay laboratory. AB - The suitability and performance characteristics of a recently introduced computer controlled laboratory workstation (Biomek 1000) for use in automating sample transfer and reagent additions in radioimmunoassay techniques were assessed. The system is based on the use of disposable tips and, therefore, reduces any possible sample carry-over and eliminates the need for priming with the subsequent reduction in cost of reagents. However, the machine lacks the useful option of liquid-level sensing facility. Acceptable technical performance in terms of precision, accuracy and throughput was obtained with the Biomek 1000 which complied with international recommendations on the safety of hospital laboratory equipment. PMID- 2208989 TI - PNSCROLL, a software package for graphical interactive analysis of single channel patch clamp currents and other binary file records: under mouse control. AB - The PNSCROLL program has been specifically developed for interactively scrolling through binary data files under mouse control, in order to analyse single channel current records and printout, or plot, records and histograms of currents. PNSCROLL requires the use of a Microsoft Mouse and runs on an IBM or IBM compatible microcomputer operating under MS DOS, ideally with 256K EGA or VGA graphics card and colour display. It will print on Epson dot matrix printers and plot records and histograms on HP plotters and LaserJet laser printers. PMID- 2208990 TI - Heterogeneous computer network for real-time hemodynamic signal processing. AB - A computer network is described that allows real-time processing, graphical monitoring and off-line analysis of blood pressure, nervous activity and Doppler signals recorded in conscious rats. Real-time processing is performed by an acquisition station using a powerful microprocessor, allowing extraction and storage of several characteristic parameters from each cardiac cycle and real time graphical monitoring. The experimenter can thereby follow the time evolution of the hemodynamic parameters. Experimental data are sent through the local network to a workstation that ensures off-line processing such as chronograms, histograms and statistical analyses. PMID- 2208991 TI - Parent-held child records. PMID- 2208992 TI - Positive treatment. PMID- 2208993 TI - Community liaison: working towards a partnership. PMID- 2208994 TI - Infant care: getting it right. PMID- 2208995 TI - Helping the stoma patient. PMID- 2208996 TI - Common pests. PMID- 2208997 TI - A sore point. PMID- 2208998 TI - Enuresis: getting dry. Interview by Catharine Sadler. PMID- 2208999 TI - The never-ending day. PMID- 2209000 TI - Politics of care: markets and spenders. Interview by Sue Smith. PMID- 2209001 TI - Your skills on video. PMID- 2209002 TI - Health promotion: HVs for the elderly. PMID- 2209003 TI - HV job-sharing. PMID- 2209004 TI - Care for the child. PMID- 2209005 TI - Studies on the contact sensitizing activity of dithranol (anthralin) and 10 butyryl dithranol (butantrone). AB - The contact sensitizing activity of dithranol and butantrone (10-butyryl dithranol) was studied in 3 animal models: the guinea pig maximization test (GPMT), the closed patch test (CPT), and the mouse ear swelling test (MEST) in 2 different mouse strains. In the GPMT, both dithranol and, to a greater extent, butantrone showed sensitizing potential. Because butantrone was less irritant, the concentrations used were 10x higher than those of dithranol. In the CPT, only butantrone was slightly positive. In the MEST, with both CF-1 and Balb/c mice, dithranol caused less swelling of the test ear after challenge than butantrone. According to the evaluation criteria of the MEST, only butantrone caused sensitization in 50% of the CF-1 mice and in 40% of the Balb/c mice. Thus, the GPMT was the only test which indicated the minor contact sensitizing potential of dithranol. On the other hand, the 10-butyryl analogue of dithranol showed undoubtedly stronger contact sensitizing potential than the parent compound in all tests. Therefore, as compared to dithranol, an increased risk of sensitization should be considered. PMID- 2209006 TI - Psoriasis-like contact dermatitis from a hair nitro dye. PMID- 2209007 TI - Contact dermatitis from disperse dyes in synthetic wigs. PMID- 2209008 TI - Contact sensitization by pesticides in farmers. AB - 30 farmers with contact dermatitis and 20 controls were patch tested with a series of locally used pesticides. Allergic reactions to 1 or more pesticides were seen in 11 patients but none of the controls. Carbamates (maneb, carbofuran, carbaryl) were the most frequent sensitizers (7 patients), followed by organophosphorus compounds like: malathion and oxydemton methyl (4 patients); 2,4 dichlorophenoxyacetic acid and fenvalerate (3 patients each); streptocycline (2 patients). Irritant reactions to captaf were seen in 4 patients, thiobencarb weedicide in 3, and organophosphorus compounds in 3. Pesticides should be patch tested in all farmers with contact dermatitis. PMID- 2209009 TI - Low allergenicity of clonidine impedes studies of sensitization mechanisms in guinea pig models. AB - During clinical trials, a clonidine transdermal device has been found to induce clonidine-specific allergic contact dermatitis in up to 25% of patients during a treatment period of 1 year. Using 3 different guinea pig strains, development was attempted of an experimental guinea pig model that would allow for in-depth studies into the mechanism of sensitization, and a possible role of transdermal device components. Transient low-level clonidine allergy could be obtained only in a minority of animals, with severe sensitization procedures departing from epicutaneous applications, combined with intradermal (adjuvant) FCA injections. Sensitization was not potentiated by additional booster procedures, including cyclophosphamide pretreatment, nor any of the putative cofactors (UV-treatments, C. parvum or acetaldehyde involvement) studied. These results suggest that the persistent skin contacts in man, with transdermal devices for sustained drug delivery, generate unique conditions favouring the development of allergic contact dermatitis, which are difficult to mimic in experimental animal models. Thus, clinical allergy may develop even to extremely weak sensitizing drugs that can be safely used orally, and escape most currently available predictive contact allergy animal models. Clinical studies remain unavoidable for studying factors that may reduce sensitization rates to more acceptable levels. PMID- 2209010 TI - Contact allergy due to colophony (VI). The sensitizing capacity of minor resin acids and 7 commercial modified-colophony products. AB - 3 minor resin acids and 7 commercial modified-colophony products of different origins were studied by experimental sensitization by means of a modified FCA method. All 3 resin acids were almost negative. The commercial products gave different results. While the maleic-modified product of Greek origin showed a strong sensitizing power, the fumaric-modified, terpene-phenol-modified and a disproportioned rosin were only moderate. A remarkable difference was obtained with the Swedish and Finnish tall oil rosins, which, in contrast to the previously studied French product, exhibited only a weak sensitizing capacity. PMID- 2209011 TI - Pregnancy diagnosis in dairy cattle: present status and future prospects. PMID- 2209012 TI - Intra-osseous pressure and pressure pulse gradients along the equine third metatarsal bone. AB - Intra-osseous pressure measurements in the third metatarsal bone of anesthetised young and mature ponies demonstrated that a pressure gradient exists along the bone, the pressure being highest at the level of the nutrient foramen and decreasing distally and proximally from this point. The height of the intra osseous pressure pulse also decreased toward the bone ends. It is concluded that the sites of measurement of the intra-osseous pressure in clinical and experimental studies should be standardized. PMID- 2209013 TI - Premature bovine parturition induced by ponderosa pine: effects of pine needles, bark and branch tips. AB - Three components of Ponderosa pine trees were administered via gavage to pregnant cows to determine their ability to induce premature parturition. When tips of branches, bark or needles were administered (2.7 kg/day) starting at 250 d of pregnancy, early parturition was induced in an average of 3.4, 5.0 and 9.1 d, respectively, compared to 31.8 d for water gavaged controls (P less than 0.01). Less pine material was required to induce parturition with tips and bark (9.4 and 11.2 kg/cow, respectively) than with needles (25.0 kg/cow P less than 0.05). Cows fed pine material retained fetal membranes longer after parturition; 13.0 d for needles, 10.5 d for bark and greater than 3.0 d for tips versus less than 0.5 d for controls (P less than 0.01). However, 2 of the cows fed tips died within 48 hours after parturition with fetal membranes intact and the other 2 cows fed tips became depressed, pyrexic and emaciated. They survived after extended veterinary care with antibiotic and fluid therapy. Administration of pine materials modified serum progesterone concentration profiles; there was significant elevation in progesterone 1-3 days after pine material was administered. Subsequently, pine material induced a premature decline in progesterone levels prior to parturition, which occurred more rapidly in cows fed bark and tips suggesting a dose response relationship. Pine material also modified serum cortisol concentration profiles; the main difference was a prolonged elevation in cows receiving tips. Branch tips and bark from Ponderosa pine are more potent in inducing parturition than needles. PMID- 2209014 TI - Two rare cutaneous neoplasms in horses: apocrine gland adenocarcinoma and carcinosarcoma. AB - Two rare equine cutaneous neoplasms, an apocrine gland adenocarcinoma and a carcinosarcoma were diagnosed in a 17-year-old pony and a 14-year-old mare, respectively. The apocrine gland adenocarcinoma was present on the prepuce. Histologically, papillary projections of low cuboidal to columnar epithelial cells were generally well differentiated, and surrounded dilated acini. Stromal invasion was present, but vascular and lymphatic invasion was not seen. The carcinosarcoma was present in the right flank of the mare. Two discrete cell populations were characterized histologically. One portion of the mass was composed of elongated, loosely arranged mesenchymatous cells; the second population consisted of dense sheets of pleomorphic, basophilic cells forming irregular acini. PMID- 2209015 TI - Management of a persistent corneal erosion in a boxer dog. AB - A dog was presented to the New York State College of Veterinary Medicine with a one-month history of corneal ulceration. The corneal lesion was diagnosed as a persistent corneal erosion (PCE) and treated initially with debridement and supported with a contact lens. One week later, the corneal erosion remained unepithelialized. Following debridement, multiple anterior stromal punctures were performed. Within 10 days, the erosion was healed as evidenced by coverage of the cornea with adherent, uninterrupted epithelium. The proposed etiology and management of PCE in dogs is discussed. PMID- 2209016 TI - Equine motor neuron disease; a preliminary report. AB - A spontaneous motor neuron disease or neuronopathy was identified in 10 horses from the northeastern United States. Signs of generalized weakness, muscle fasciculations, muscle atrophy and weight loss progressed over 1 to several months in young and old horses of various breeds. Pathologic studies revealed that degeneration and loss of motor neurons in the spinal cord and brain stem resulted in axonal degeneration in the ventral roots and peripheral and cranial nerves and denervation atrophy of skeletal muscle. Many spinal neurons were swollen, chromatolytic and contained neurofilamentous accumulations. Other cell bodies were shrunken and undergoing neuronophagia and some were lost and replaced by glia. This fatal equine motor neuron disease has not been reported previously and its cause has not been determined. The progressive weakness and wasting and the neuronal degenerative changes in these horses were similar to those described in people with sporadic amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. PMID- 2209017 TI - Nonsteroidal management of canine pruritus: chlorpheniramine and a fatty acid supplement (DVM Derm Caps) in combination, and the fatty acid supplement at twice the manufacturer's recommended dosage. AB - Forty-three dogs having pruritus associated with atopy, flea bite hypersensitivity, and idiopathy were randomly assigned to 1 of 2 treatment protocols. Twenty-three dogs received chlorpheniramine in combination with a fatty acid supplement (DVM Derm Caps). Twenty dogs received the fatty acid supplement at twice the manufacturer's recommended dosage. All 43 dogs were known to be unresponsive to chlorpheniramine and the manufacturer's recommended dosage of the fatty acid supplement when either drug was used alone. Pruritus was satisfactorily controlled in 34.8% of the dogs in the chlorpheniramine--DVM Derm Caps protocol. No dog in the double DVM Derm Caps protocol showed a beneficial response. Side effects were uncommon and mild with either protocol. PMID- 2209018 TI - Vth International Symposium on Pulmonary Circulation. Prague, 4-7 July 1989. Proceedings. PMID- 2209019 TI - Non-invasive diagnosis of pulmonary hypertension and activities pursued by a working group of the World Health Organization. PMID- 2209020 TI - Reflux pulmonary vein flow prevents pulmonary infarction after pulmonary artery obstruction. AB - Kuttner showed in 1874 that simultaneous ligation of the pulmonary veins increased the frequency and severity of lung infarctions after pulmonary artery obstruction. The authors studied the possibility that a tidal pulmonary venous blood flow reflux from the left atrium could nourish the alveolar tissue. This could be driven by left atrial pressure transients and alternate expansion and compression of alveolar and extra alveolar vessels due to tidal lung volume changes. 5 anesthetized, closed chest goats were studied in the prone position after left pulmonary artery ligation and the obstruction of all bronchial blood flow to the left lung, checked by systemic microsphere injection. The inert, insoluble gas SF6 was infused into the left atrium and the exhaled gas from left and right lungs was collected separately. SF6 was found in the gas exhaled from the left lung, showing that left atrial blood had reached the alveolar tissues. The effective reflux blood flow was increased from control levels (no ventilation, normal left atrial pulses) by tidal volume changes, and by increased left atrial pressure transients (balloon induced mitral insufficiency). This venous reflux flow could explain why alveolar tissues do not suffer more severe injury when the pulmonary artery is obstructed. PMID- 2209021 TI - Coil embolization of pulmonary arteriovenous malformations. AB - Sixteen patients with pulmonary arteriovenous malformations (PAVM) have been treated by percutaneous transvenous coil embolization. In the ten patients who have had all their angiographically demonstrable PAVM's embolised there has been a reduction of right to left shunting from a mean of 28.1% to 13% and an improvement in mean arterial oxygen saturation from 87.4% to 92.4%. Eight of these ten patients now have oxygen saturations of more than 90%. All patients have shown symptomatic improvement. There have been three complications relating to the embolizations, none of which has been serious. Coil embolization of PAVM's is an effective, safe and well tolerated procedure. Embolization should be performed in all cases of PAVM's to prevent paradoxical embolization. PMID- 2209022 TI - Right ventricle in patients after orthotopic heart transplantation. AB - Eighteen patients were examined by echocardiography one month before, and one month after orthotopic heart transplantation (OHT). The right-heart echocardiographic parameters were compared with pulmonary haemodynamics. All recipients showed increased mean pulmonary artery pressure (PAP) (42 +/- 8 mmHg) and pulmonary vascular resistance 3.0 +/- 1.3 u.) before OHT. The causes of the pulmonary hypertension, and indications for OHT, were the end stage of dilated cardiomyopathy (n = 8), ischaemic heart disease (n = 9) and aortic valve disease (n = 1). After transplantation, the donor's right ventricle dilates due to the recipient's elevated pulmonary vascular resistance. The right ventricular dimension after OHT was greater than 30 mm in 1/3 of patients. The right ventricular diastolic dimension correlates statistically significantly with mean PAP of the recipient before the procedure. Right ventricular dilatation is accompanied by a mild degree of tricuspid insufficiency (in 89% of cases), as documented by Doppler examination. Neither the degree of right ventricular dilatation, nor the degree of tricuspid insufficiency show a tendency to progression during follow-up. PMID- 2209023 TI - Dynamic pulmonary arterial hypertension: a new form of pulmonary hypertension in patients with impaired pulmonary diffusing capacity due to toxic oil syndrome. AB - The authors studied the pulmonary haemodynamic response to exercise in eleven patients with toxic oil syndrome (TOS) (mean age 38.3 +/- 15.7 years; 10 women, 1 man) and abnormal pulmonary diffusing capacity (39.1 +/- 10.3% of predicted value) without clinical evidence of pulmonary hypertension. Eight patients had normal pulmonary pressure at rest (mean PAP less than 25 mmHg) and three showed mild pulmonary hypertension. After exercise the mean PAP rose to 35.3 +/- 11.5 mmHg from a basal value of 20.72 +/- 3.8 mmHg (p less than 0.01). Only four patients did not develop pulmonary hypertension during exercise. Pulmonary artery oxygen saturation decreased from 72.9 +/- 1.9% at rest to 52.3 +/- 10.1% during exercise (p less than 0.01). In conclusion, in this subset of TOS patients, an early diagnosis of their subclinical pulmonary hypertension can be made on the basis of the presence of dyspnoea and abnormal pulmonary diffusing capacity for carbon monoxide and can be then confirmed with the exercise haemodynamic test. PMID- 2209024 TI - Severe pulmonary arterial hypertension due to toxic oil syndrome: a new cause of plexogenic arteriopathy. AB - Ten patients with severe pulmonary hypertension due to Toxic Oil Syndrome (TOS) (3 men, 7 women; mean age 27.9 +/- 11.23 yrs.) are presented. The pulmonary vessels were examined with a micromorphometric technique. All patients had intimal fibrosis of the arteries and veins. Seven also had a thrombus in different stages. All arteries were shown to have medial hypertrophy. Plexiform lexions were found in eight cases. It is concluded that TOS can produce severe pulmonary hypertension histologically undistinguishable from the primary form. TOS can be added to the list of diseases causing plexogenic arteriopathy. PMID- 2209025 TI - Acute effect of intrapulmonary enalaprilat in ten patients with severe pulmonary hypertension due to toxic oil syndrome. AB - Ten patients with severe pulmonary hypertension due to Toxic Oil Syndrome underwent cardiac catheterization to analyse the acute effect of intrapulmonary injection of 1.25 mg of enalaprilat. Haemodynamic parameters were obtained at basal state, 15, 30, 45 and 60 minutes after administration of the drug. Enalaprillat did not produce any statistically significant changes in pulmonary pressures and resistances or cardiac output. This lack of response is unknown but may be related to the presence of endothelial damage and fixed pulmonary vascular lesions observed at autopsy in three patients. PMID- 2209026 TI - The bronchial arteries of the dog after selective embolization of the pulmonary artery with emboli of various size. A morphological study. AB - The aim of the study was to investigate whether the development of collateral broncho-pulmonary circulation depends on the size of obliterated branches of the pulmonary artery. Massive embolization of the pulmonary arterial bed was performed with sterile plastic spheres of known size from 0.08 to 1.0 mm in diameter in 25 dogs. Three months after embolization, the bronchial arteries were investigated with the use of post mortem bronchial arteriography and histology. The same investigation of the bronchial arteries was performed in 6 control dogs with intact pulmonary circulation. Bronchial arteriography showed conspicuous dilatation of the bronchial arteries in all dogs in which the emboli of 0.4, 0.6 and 1.0 mm in diameter were used for pulmonary artery embolization. Embolization with spheres of 0.08, 0.175 and 0.3 mm in diameter did not cause any enlargement of the bronchial arteries. They were of the same size as those in control dogs. Histological investigation revealed that the bronchial arteries were enlarged and hypertrophic in all dogs which the elastic branches of the pulmonary artery had been occluded. The bronchial arteries never showed an increase in size in case of embolization of muscular arteries or arteriolae. The results showed that the development of collateral bronchopulmonary circulation in the dog depends on the size of the occluded branch of the pulmonary artery. PMID- 2209027 TI - 5th International Symposium on Pulmonary Circulation. PMID- 2209028 TI - Results of an epidemiological study of the prevalence of arterial hypertension among employees of selected plants in Moscow and Plzen. A cooperative study. AB - The quality of medical care provided especially to patients with arterial hypertension employed in three industrial plants (ZIL Automobile Works, Moscow, Mytishchi Machine Works, and Skoda Works, Plzen, Czechoslovakia) was investigated in random samples of male and female employees aged 35-64 years. The lowest prevalence of hypertension (AH) was found in Skoda Works (26.4 +/- 1.3%). A standardized cooperative epidemiological study detected a low percentage of treated AH cases and insufficient efficacy of treatment in all three plants, especially among young male hypertensives. The epidemiological status of AH in the ZIL and Mytishchi Works was less favourable compared with that in Skoda Works. Epidemiological data represent an indispensable basis for developing a scientific approach to primary and secondary prevention of AH. PMID- 2209029 TI - The effect of ibustrin on early aortocoronary bypass patency. AB - Results of a randomized study designed to compare the effect of ASA and dipyridamole with that of Ibustrin on early patency of low-flow aortocoronary bypasses are presented. The study included 49 patients in whom at least one of the bypasses showed an intraoperative blood flow rate of 40 ml/min or less, i.e., reconstructions at highest risk of early thrombosis. Of 39 bypasses in the ASA and dipyridamole group, 11 (28.2%) were occluded and, in the Ibustrin group, eight (25.8%) out of 31 bypasses were found to be occluded on the angiogram performed 7-10 days postoperatively. There is no statistically significant difference in the patency rate between these two groups. Administration of Ibustrin was not associated with any side effects, and leads to the same improvement of early ACB patency as administration of ASA and dipyridamole. PMID- 2209030 TI - Sepsis-related cardiogenic shock. AB - To further define cardiovascular abnormalities in patients with septic shock, serial conventional hemodynamic measurements combined with two-dimensional echocardiographic studies were performed at the bedside in 21 patients admitted for an acute episode of sepsis-related circulatory failure. Measurements obtained during the first hours of hospitalization revealed a group of six patients (group 1) with markedly depressed left ventricular function, as evidenced by a low cardiac index (CI) (2.2 +/- 0.8 L/min.m2), reduced left ventricular ejection fraction (LVEF) (21 +/- 8%), and an increased arterial-venous oxygen content difference. Right ventricular systolic function was also severely depressed. These patients were characterized as having sepsis-related cardiogenic shock secondary to profound myocardial depression, which was reversible within 24 to 48 h with inotropic support. The 15 remaining patients (group 2) exhibited an initially increased CI (4.9 +/- 1.8 L/min.m2), with a low systemic vascular resistance. In group 2, LVEF remained within the normal range despite abnormally low peripheral vascular resistance. This finding would suggest the presence of slight to moderate depression of left ventricular systolic function. All patients in this series had a normal left ventricular end-diastolic volume, whether profound myocardial depression was present or not. PMID- 2209031 TI - Use of a computerized closed-loop sodium nitroprusside titration system for antihypertensive treatment after open heart surgery. AB - This study evaluates the clinical applicability of administering sodium nitroprusside by a closed-loop titration system compared with a manually adjusted system. The mean arterial pressure (MAP) was registered every 10 and 30 sec during the first 150 min after open heart surgery in 20 patients (group 1: computer regulation) and in ten patients (group 2: manual regulation). The results (16,343 and 2,912 data points in groups 1 and 2, respectively), were then analyzed in four time frames and five pressure ranges to indicate clinical efficacy. Sixty percent of the measured MAP in both groups was within the desired +/- 10% during the first 10 min. Thereafter until the end of observation, the MAP was maintained within +/- 10% of the desired set-point 90% of the time in group 1 vs. 60% of the time in group 2. One percent and 11% of data points were +/- 20% from the set-point in groups 1 and 2, respectively (p less than .05, chi-square test). The computer-assisted therapy provided better control of MAP, was safe to use, and helped to reduce nursing demands. PMID- 2209033 TI - Catheter-related sepsis: prospective, randomized study of three methods of long term catheter maintenance. AB - We studied the infectious risk of different methods of managing vascular catheters during long-term use. Consecutive surgical ICU patients requiring triple lumen catheters, pulmonary artery catheters, or arterial catheters for greater than 7 days were prospectively randomized to one of three management groups: a) percutaneous (PERC) puncture with every 7-day catheter change at a new site, b) no weekly change (NWC) with a new site when changed, or c) guidewire exchange (GWX) with every 7-day catheter change at the same site. In all groups, a catheter change was mandatory for a positive blood culture, skin site infection, or sepsis without a likely source. Cultures were obtained when clinically indicated and at the time of every catheter change. Catheter-related sepsis (CRS) was defined as a positive blood culture and catheter culture with the same organism. A total of 112 patients met evaluation criteria. There were no intergroup differences in age, primary diagnosis, severity of injury or illness, number of study days, number of protocol violations, route of catheterization, number of catheters present/patient day, catheter sepsis rate, or bacteremia rate. The NWC group demonstrated an increased number of days/catheter, fewer catheter/subcutaneous tract segment cultures/patient, and a reduced incidence of catheter tip colonization. These results occurred in a setting where the number of CRS episodes/patient was 0.17 for GWX, 0.22 for PERC, and 0.16 for NWC. We conclude that there is no difference in infectious risk between these three methods of long-term catheter management. The method with the least complications and expense should be used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2209032 TI - Oximetry in children recovering from deep hypothermia for cardiac surgery. AB - Although pulse oximetry is a potentially useful diagnostic tool in the treatment of children after major open heart surgery, there are concerns regarding its reliability for measuring oxygen saturation (SaO2) in hypothermic or low perfusion states. To test pulse oximeter reliability in children under these conditions, our study compared 187 SaO2 pulse oximeter readings (Biox 3700) with simultaneous hemoximeter (OSM2, Radiometer) readings from 56 children rewarming after open heart surgery. Ages ranged from 4 months to 18 yr; temperatures ranged from 23.5 degrees to 38 degrees C (toe) and 31.3 degrees to 40.8 degrees C (core). The mean pulse oximeter SaO2 reading was 94.90% (SD 7.18, range 54% to 100%), mean hemoximeter reading was 96.07% (SD 7.06; minimum 54%; maximum 100%). The correlation between the readings was high (r = .88, p less than .005), and was not affected by low core temperature. When oximeter and cardiac monitor pulse rates coincided, the oximeter SaO2 value was within +/- 5% (p less than .05). We conclude that the Biox 3700 oximeter is reliable for noninvasive SaO2 monitoring in mild to moderately hypothermic children after open heart surgery, particularly when oximeter and cardiac heart rates coincide. Further studies are needed to confirm our findings in children with core temperatures less than 31.3 degrees C, and when other oximeters are used. PMID- 2209034 TI - Flow and volume dependence of respiratory system mechanics during constant flow ventilation in normal subjects and in adult respiratory distress syndrome. AB - Seven control subjects and seven patients with adult respiratory distress syndrome (ARDS) were artificially ventilated and flow, volume, and tracheal pressure were monitored. Respiratory system resistance (Rrs,max) was partitioned into its homogeneous (Rrs,min) and uneven (Rrs,u) components. Respiratory system elastance (Ers) was also measured. In both groups Ers did not vary with different inspiratory flows and volumes, but was significantly higher in ARDS. With increasing volume (isoflow maneuvers), Rrs,max and Rrs,u increased but Rrs,min remained unaltered in ARDS. In control patients, however, resistances did not vary but Rrs,max and Rrs,u were smaller and Rrs,min equaled their corresponding values in ARDS. Hence, stress relaxation seems to be increased in ARDS. During isovolume maneuvers Rrs,max and Rrs,u decreased with increasing flows (both groups), although they were significantly higher in ARDS. Rrs,min was not modified by different flows and was similar in both groups. Thus, pendelluft is also increased in ARDS. In conclusion, the mechanical profile of ARDS is characterized by increased Ers and Rrs,max, the latter being secondary to augmented mechanical unevenness within the system. PMID- 2209035 TI - Effect of blood transfusion on oxygen consumption in pediatric septic shock. AB - Treatment plans for pediatric septic shock advocate increasing oxygen consumption (VO2). Recent studies in septic shock indicate that improving oxygen delivery (DO2) by increasing blood flow will increase VO2. We prospectively examined the effect on VO2 of improving DO2 by increasing oxygen content (CO2) with blood transfusion in eight hemodynamically stable septic shock patients. Transfusion consisted of 8 to 10 ml/kg of packed RBC over 1 to 2 h. Hemodynamic and oxygen transport measurements were obtained before and after blood transfusion. Transfusion significantly (p less than .05) increased Hgb and Hct from 10.2 +/- 0.8 g/dl and 30 +/- 2% to 13.2 +/- 1.4 g/dl and 39 +/- 4%, respectively (mean +/- SD). DO2 significantly (p less than .05) increased after transfusion (599 +/- 65 to 818 +/- 189 ml/min.m2), but VO2 did not change (166 +/- 68 to 176 +/- 74 ml/min.m2; NS). In pediatric septic shock patients, increasing CO2 by blood transfusion may not increase VO2. PMID- 2209036 TI - Pulmonary volume measurements during high-frequency jet ventilation in anesthetized man. AB - To assess the validity of indirect spirometry during conventional intermittent positive-pressure ventilation (IPPV) and high-frequency jet ventilation (HFJV), we measured changes in functional residual capacity (delta FRC) and tidal volume (VT) with two external strain gauges in eight sedated and paralyzed patients. The thoracic and abdominal gauges were calibrated simultaneously in quasi-static and dynamic conditions. The delta FRC measured during HFJV (1 to 5 Hz) and the VT measured during IPPV (0.25 Hz) were found to be equivalent by the two gauges in most patients (r = .90 and r = .99, respectively), but no correlation was found between the VT values inferred by each gauge in HFJV (r = .54). During HFJV, spectral analysis of the gauge signals showed important damping of the abdominal motion (AB) and an amplification of the thoracic displacements (RC) in four patients when measurements were taken at greater than 3 Hz. We conclude that, provided the partition of the volume between AB and RC remains constant, indirect spirometry may measure VT in IPPV and delta FRC in HFJV, but it fails to measure VT accurately during HFJV. PMID- 2209037 TI - Hemodynamic and metabolic effects of dobutamine in 18 patients after open heart surgery. AB - Low cardiac output syndrome frequently follows cardiopulmonary bypass (CPB) surgery. In the present study, we used dobutamine to increase cardiac index (CI) and oxygen delivery (DO2) in 18 patients after open heart surgery. Using increasing doses of dobutamine up to 10 micrograms/kg.min-1, we observed statistically significant (p less than .01) increases in mean CI (2.50 +/- 0.10 to 3.56 +/- 0.18 L/min.m2) and in mean heart rate (HR) (83 +/- 3 to 105 +/- 3 beat/min). Mean systemic vascular resistance index decreased significantly (p less than .01) in all patients (2271 +/- 101 to 1648 +/- 83 dyne.sec/cm5.m2). Pulmonary vascular resistance index did not change in the ten coronary artery bypass graft patients, but decreased significantly (p less than .01) in the eight valve replacement patients (561 +/- 98 to 421 +/- 79 dyne.sec/cm5.m2). Mean DO2 increased in all patients, although there was no concomitant increase in oxygen consumption (VO2) in four patients. We observed a significant (p less than .01) increase in mean VO2 in the remaining 14 patients (110 +/- 6 to 148 +/- 12 ml/min.m2), in spite of significant decreases in PaO2 and increases in right-to left intrapulmonary shunting. Although increases in HR and ventricular arrhythmias may limit its use, dobutamine increases CI and DO2 in patients after CPB. In the present study, dobutamine's varying metabolic effect exemplifies the need for close monitoring of hemodynamic and metabolic variables when using vasoactive drugs in the postoperative period. PMID- 2209038 TI - Outcome prediction models on admission in a medical intensive care unit: do they predict individual outcome? AB - Prospectively acquired data from 941 patients staying greater than 24 h in a medical ICU were analyzed to determine the relevance of scoring on ICU admission by the following methods of outcome prediction: Acute Physiology and Chronic Health Evaluation (APACHE II), Simplified Acute Physiology Score (SAPS), and Mortality Prediction Model (MPM). Analysis was performed separately for all patients (group A) and for a subsample (group B), obtained by excluding coronary care patients. Calculation of risk and classification of patients were carried out as recommended in the literature for MPM, APACHE II, and SAPS. In group A, sensitivities (correct prediction of hospital mortality) were 44.7%, 51.1%, and 21.2% and specificities (correct prediction of survival) were 84.5%, 85.4%, and 96.8%, respectively; overall correct classification rates were 73.3%, 75.8%, and 75.6%. In group B, sensitivities were slightly higher, but total correct classification rates did not reach group A levels. Goodness-of-fit testing showed low levels of fit for all methods in both groups. Application of APACHE II to diagnostic subgroups, using disease-adapted risk calculations, revealed marked inconsistencies between the estimated risk and the observed mortality. We conclude that the estimation of risk on admission by the three methods investigated might be helpful for global comparisons of ICU populations, although the lack of disease specificity reduces their applicability for severity grading of a given illness. The inaccuracy of these methods makes them ineffective for predicting individual outcome; thus, they provide little advantage in clinical decision-making. PMID- 2209039 TI - Rapid acute physiology scoring in transport systems. AB - A multi-institutional study was undertaken to define the predictive power for mortality of the Rapid Acute Physiology Score (RAPS) in a large and diverse group of transported patients. RAPS is a truncated version of the Acute Physiology and Chronic Health Evaluation (APACHE II) score that uses definitions and weighting consistent with APACHE II, but is modified to provide a consistent score just before transport, just after transport, and to use the most deranged (worst) physiologic values during the initial 4 h after arrival at the receiving hospital. During an 8-month period, 1,927 patients transported by six helicopter emergency medical service programs were studied. Over 97% (1,881) of the patients had RAPS obtained before and after transport to the receiving hospital and 92.6% (1,785) had APACHE II scoring completed after hospital admission. Receiver operating curves demonstrate similar predictive power for RAPS and APACHE II (both based on the most deranged physiologic values during the initial 24 h after admission). Before- and after-transport RAPS were also highly predictive of mortality. RAPS appears to be a reliable and highly predictive measure of patient severity/physiologic stability before and after transport to critical care. PMID- 2209040 TI - Critical care for clonidine poisoning in toddlers. AB - Clonidine may be a source of serious toxicity when ingested by toddlers. We describe 11 cases of clonidine ingestion by toddlers (mean dose 0.15 mg/kg; range 0.01 to 0.57). The source of the clonidine was a grand-parent in six of 11 cases. Symptoms included altered level of consciousness (n = 11), miosis (n = 5), bradycardia (n = 8), hypotension (n = 5), apnea and respiratory depression (n = 6), hypothermia (n = 5) and hypertension (n = 3). Therapeutic interventions included naloxone (n = 8) and atropine (n = 4), dopamine (n = 1), fluid resuscitation (n = 4), and endotracheal intubation (n = 1). There were no deaths. Symptoms of clonidine ingestion were typically mild if the dose ingested was less than 0.01 mg/kg, while bradycardia and hypotension occurred usually with doses of greater than 0.01 mg/kg. Apnea and respiratory depression were common when the dose exceeded 0.02 mg/kg. More effective measures are needed to prevent these potentially serious intoxications. PMID- 2209041 TI - Role of prostaglandin E1 in reducing pulmonary vascular resistance in an experimental model of acute lung injury. AB - To determine the role and efficacy of prostaglandin E1 (PGE1) on the cardiopulmonary derangements induced by glass bead embolism, two studies were performed. In the first study, a dose response of PGE1 was tested in six animals that were first embolized with sufficient glass beads to double the pulmonary artery pressure (PAP). This study demonstrated that PGE1 reduced PAP and cardiac output by a preload-mediated mechanism, as evidenced by a reduction in the right ventricular (RV) end-diastolic segment length, at doses of 15 and 30 ng/kg.min. The second study was performed in two groups of animals, the control group (n = 6), and the treated group (n = 6), which were given PGE1 at 15 ng/kg.min after the PAP had been doubled by glass bead embolism. RV preload was kept constant. This study demonstrated that there was no difference in pulmonary vascular resistance between either the treated group or the control group. There were no other significant differences between the two groups. The results of both of these studies suggest that there is little afterload reducing effect of PGE1 in this model and at these dose ranges. Part of the mechanism of PGE1 that improves pulmonary edema and gas exchange may be the reduction of filtration surface area and hydrostatic pressures in the lungs. PMID- 2209042 TI - Plasma epinephrine levels in resuscitation with cardiopulmonary bypass. AB - Since the highest plasma epinephrine levels have been recorded during resuscitation, we evaluated the isolated effect of cardiac arrest upon adrenomedullary secretion. We determined plasma epinephrine in dogs resuscitated with cardiopulmonary bypass (CPB) after cardiac arrest periods of 12 (CPB-12; n = 4) or 16 min (CPB-16; n = 5). Through 2 h of CPB and the following 6 h of critical care, there was no difference between CPB-12 and CPB-16 regarding most cardiopulmonary functional variables. Plasma epinephrine was markedly elevated immediately after initiation of CPB (p less than .01 at 1 min CPB vs. basal) and returned rapidly to basal concentrations. Comparison of plasma epinephrine levels between CPB and standard CPR groups showed that responses to cardiac arrest were similar (p greater than .05 at 1 min CPB vs. 11.5 min CPR). We conclude that cardiac arrest is the main or sole determinant of the plasma epinephrine elevation of resuscitation. PMID- 2209043 TI - Rapid admixture blood warming: technical advances. AB - The technique of rapid admixture blood warming of cold erythrocyte units is designed to warm erythrocyte units rapidly (less than 30 sec) while simultaneously providing saline for dilution. However, questions have been raised about the recommended use of a standard 250-ml bolus of 70 degrees C admixture saline, the uniformity and speed of blood unit warming, the difficulties inherent in keeping saline bags at 70 degrees C, and the safety of the methodology. To answer these questions, a series of tests were performed and modifications of the technique were introduced. The mean weight of 1000 successive units of erythrocytes for adult infusion was 305 g (range 220 to 410). The maximum temperature was 44 degrees C, using an internal temperature probe (1-cm temperature gradations; 2-sec recording intervals) when the smallest unit was admixed with a 250 ml 70 degrees C saline bolus; the largest unit had a minimum temperature of 30 degrees C. Plasma Hgb, osmotic fragility, and K of the minimum size erythrocyte unit showed no significant deviation from its control. Both thermographic photographs and the internal temperature recordings of the erythrocyte units demonstrated that solely due to fluid turbulence, uniform mixing occurs within approximately 30 sec of beginning the admixture process. Inverting the blood units caused a thermal layering of fluids and an unacceptable maximum blood temperature of 50 degrees C. There was no difference between the mixing time or efficacy in the presence of standard or large-bore iv tubing or additional in-line filters. Volumes of the 250-ml saline bags for admixture decreased markedly with deviations in electrolyte composition after greater than 2 wk at 70 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2209044 TI - Peripheral venous monitoring with acute blood volume alteration: cuff-occluded rate of rise of peripheral venous pressure. AB - We investigated the use of a new peripheral hemodynamic monitoring technique, the cuff-occluded rate of rise of peripheral venous pressure (CORRP), in the assessment of volume status in fluid overload. Seven adult mongrel dogs were given a general anesthetic, and monitoring lines were inserted. The animals were then subjected to an incremental volume overload of approximately 13% of estimated initial blood volume at 5-min intervals until a total volume infusion nearly equal to the animal's initial blood volume was reached. Comparison of the various monitoring techniques (e.g., cardiac output, CVP, systemic BP, pulmonary wedge pressure) demonstrated that the peripheral measurement of CORRP had better correlation with known administered volume (r = .96) than any of the other variables. The sensitivity of each of the variables in assessing small amounts of volume overload was also studied. The volume of crystalloid infusion necessary to cause a clinically significant change (defined as greater than 2 SD above the baseline mean) was compared for each of the monitoring variables. CORRP was equivalent to the other variables in sensing early volume overload. In summary, in the anesthetized animal model CORRP appears to be a sensitive, minimally invasive method of assessing volume status in acute volume overload. The efficacy of CORRP in a canine hemorrhagic shock and reperfusion model had previously been demonstrated. This technique could be clinically applicable in situations such as trauma with hemorrhagic shock, intraoperative volume changes, and in the assessment of intravascular volume after resuscitation. PMID- 2209045 TI - Effect of hemodilution on capillary and arteriolovenous shunt flow in organs after cardiac arrest in dogs. AB - The purpose of this study was to observe the changes in capillary and arteriolovenous shunting blood flow after cardiac arrest and subsequent resuscitation by venous return occlusion produced by inflation of an intra-atrial balloon and cross-clamping of the ascending aorta, and to determine how hemodilution might modify such changes. Organ capillary blood flow and the fractional distribution of cardiac output were measured by the microsphere (9 microns diameter) trapping method in dogs. Simultaneously, the arteriolovenous shunt rate was measured by continuous collection of venous blood drained at 4.8 ml.min-1 for 2 min from the brain, kidney, liver, splanchnic organs, skeletal muscle of the pelvic limb, and all of the systemic circulatory organs. The capillary blood flow of the brain, thyroid gland, pancreas, and stomach decreased after circulatory arrest in five nonhemodiluted dogs (group C); arteriolovenous shunt rate was unchanged after circulatory arrest in this group. However, with hemodilution, which was induced either before (pre group, n = 5) or after (post group, n = 5) circulatory arrest, no change occurred in the shunt rate in any of the organs, with the exception of an increase in the systemic arteriolovenous shunt rate in the pre group. Capillary blood flow was maintained at almost the same level as before circulatory arrest in the pre group, but increased significantly in several organs of the post group. The data indicated that hemodilution might be effective for prevention of organ ischemia after cardiac arrest. PMID- 2209046 TI - Bronchial blood flow reduction with positive end-expiratory pressure after acute lung injury in sheep. AB - Smoke inhalation increases bronchial blood flow (Qbr) and produces edema of the airway system. This study investigates whether the increased Qbr seen 24 h after inhalation injury can be affected by mechanical ventilation with PEEP (5, 10, 15 cm H2O). Sheep (n = 8) previously prepared with cardiopulmonary catheters and ultrasonic transit time flow probes mounted around their bronchial arteries were insufflated with four sets of 12 breaths each of cotton smoke. Different levels of PEEP were added to the mechanical ventilation 24 h after injury; each PEEP level was applied for 45 min. There were significant increases in Qbr and lung lymph flow (QL) associated with a marked decrease in bronchial vascular resistance (BVR) 24 h after injury. However, no change was observed in mean arterial pressure (MAP) or cardiac index (CI). There was a substantial reduction in PaO2/FIO2 (P/F), which indicated a deterioration in arterial oxygenation. The application of varying levels of PEEP decreased Qbr (p less than .05) while BVR increased (p less than .05), but QL and P/F did not. CI and MAP were recorded. After removal of PEEP, none of the cardiopulmonary variables were significantly different from their postsmoke control values. These findings suggest that mechanical ventilation with PEEP markedly decreases the smoke-induced hyperemia edema frequently seen after inhalation injury without any significant alterations in MAP or CI. PMID- 2209047 TI - Noninvasive determination of pulmonary artery wedge pressure: comparative analysis of pulsed Doppler echocardiography and right heart catheterization. AB - To compare left ventricular filling variables as derived by transmitral pulsed Doppler echocardiography (tpDE) and hemodynamic variables as assessed at right heart catheterization (RHC), 104 ICU patients (64 male, 40 female) aged 26 to 73 yr (mean 54.6 +/- 10.3) without valvular heart disease were examined. Simultaneously with RHC, transmitral flow velocity profiles were obtained by tpDE, and the ratio of the velocity-time integrals of late diastolic active (A wave) and early diastolic passive inflow into the left ventricle (E wave) was calculated (A/E ratio). Invasively determined pulmonary capillary wedge pressure (WP) ranged from 3 to 36 mm Hg (median 13.35, 5%/95% 6/31 mm Hg). Linear regression analysis showed a highly significant correlation between the A/E ratio and WP (r = .98, p less than .001, standard error of the estimate [SEE] = 0.10). The A/E ratio also correlated with other hemodynamic variables such as cardiac output (r = -.68, p less than .001, SEE = 0.33), cardiac index (r = -.74, p less than .001, SEE = 0.31), and stroke volume index (r = -.68, p less than .001, SEE = 0.34). The interobserver agreement (derived by intraclass correlation analysis between two examiners) on the A/E ratio was high (r = .95, p less than .001, n = 26). We conclude that WP can be accurately determined noninvasively by tpDE. For the assessment of systolic ventricular function, tpDE is of limited diagnostic value. PMID- 2209048 TI - Kinin/prostaglandin system: its therapeutic value in surgical stress. AB - Multiple system organ failure as a consequence of injury or sepsis remains the major reason for death in critically ill patients. One of the treatment concepts that has recently attracted clinical attention is the administration of kinins and prostaglandins (PGs). On the basis of experimental data, there is reason to believe that these compounds may have the potential to manipulate favorably certain processes and mechanisms (such as inflammatory or ischemic reactions) thought to be important in the pathophysiology of surgical stress. However, thus far, information on those effects in humans is still scarce. On the other hand, administration of kinins and PGs is technically possible and can be performed safely, even in intensive care patients. Therefore, different techniques, effects, and side-effects of kinin/PG therapy deserve clinical testing. It remains to be seen whether this concept will be useful in the treatment of critically ill surgical patients. PMID- 2209049 TI - Streptococcus pneumoniae bacteremia associated with near-drowning. PMID- 2209051 TI - Myocardial depression during septic shock in humans. PMID- 2209050 TI - Acute thrombotic accident in the postpartum period in a patient receiving bromocriptine. PMID- 2209052 TI - Use of survivors' cardiorespiratory values as therapeutic goals in septic shock. PMID- 2209053 TI - Percutaneous central venous catheterization in a pediatric intensive care unit: a survival analysis of complications. PMID- 2209054 TI - Acronym-associated illness. PMID- 2209055 TI - Complications of pulmonary artery catheter insertion. PMID- 2209056 TI - Subclavian introduction technique of the pulmonary artery catheter. PMID- 2209057 TI - Who needs the respiratory index/pulmonary shunt relationship? PMID- 2209058 TI - Prevention of pneumonia in an intensive care unit. PMID- 2209060 TI - Attitude of pediatric intensivists toward prophylaxis of upper gastrointestinal bleeding. PMID- 2209059 TI - Ketanserin in the treatment of pulmonary hypertension after valvular surgery: comparison with sodium nitroprusside. PMID- 2209061 TI - Continuous infusion H2-receptor therapy. PMID- 2209062 TI - Potential value of collagen shields as a subconjunctival depot release system. AB - Collagen shields are fabricated from dissoluable porcine scleral tissue and have been used as an ocular drug delivery system. The aim of the present study was to determine the time and extent of shield absorption when implanted subconjunctivally, and the absorption and release of 5-fluorouracil in vitro. Thirty New Zealand white rabbit eyes were employed. BioCor 72 hour collagen shields were surgically implanted in the subconjunctival space. Rabbits were sacrificed at 7, 14 and 21 days after shield implantation, and the remaining shields removed. Remaining shields were measured by both dry weight and protein assay. The absorption and release of 5-FU from collagen shields was determined in vitro using tritiated 5-FU. The collagen shields were not fully absorbed for at least 14 days in the subconjunctival space. In vitro, 5-FU absorbed by the shields reached saturation levels at approximately 15 minutes. Nearly 100% of the 5-FU was released within 15 minutes. Although the time for subconjunctival shield absorption may be useful for antifibroblast drugs, the rate of 5-FU release from these shields is not optimal for enhancing bleb formation when shields are soaked in solutions of 5-FU. PMID- 2209063 TI - Effects of hemicholinium-3 on the pigmented rabbit retina and pigment epithelium. AB - Hemicholinium-3 effects on the albino rabbit neural retina have been described, but effects on the retinal pigment epithelium (RPE) have not been closely examined. We have studied retinal morphology and function in Dutch belted (pigmented) rabbits after single intravitreal injections of Hemicholinium-3 or saline. DC electroretinogram recordings show a decrease in a, b, and c-wave amplitudes, with the c-wave affected first. Experiments with sodium iodate show that the early decrease in the c-wave results from a loss of the RPE component of the c-wave, rather than the retinal Slow PIII component. After two days, ophthalmoscopic abnormalities of the fundus are severe in a large area with pigmentary changes. A sharp boundary appears between normally pigmented and depigmented fundus, indicative of a critical threshold for damage. The RPE contains clumped melanin. Pigmented cells are seen away from the basement membrane, an early histological observation temporally correlated with a loss of barrier function seen in fluorescein angiograms. After 10 days, apparent proliferation of non-pigmented RPE cells coincides with re-establishment of the barrier. Rod photoreceptor outer segments are lost 4-7 days after injection in the depigmented regions of the fundus, but outer segments are spared in normally pigmented fundus areas. This regional pattern is distinct from that seen in albino rabbit retina where outer segment loss is fairly uniform. We conclude that Hemicholinium-3 affects the RPE in pigmented rabbits in addition to known effects on retinal cholinergic neurons and photoreceptor disc synthesis. PMID- 2209064 TI - The release of a neutrophil chemotactic factor from UV-B irradiated rabbit corneas in vitro. AB - Rabbit corneas were isolated, mounted on plastic rings to form a cup and the endothelium was covered with RPMI tissue culture medium. The preparation was then irradiated with 1 J. cm-2 of 300 nm light over 1 hour and then incubated for a further two hours in the dark. The supernatant fluid was assayed for chemotactic activity toward rabbit neutrophils in an in vitro Boyden chamber assay. The results indicated that medium from irradiated corneas had a chemotactic activity that was 42% of that produced by the standard chemoattractant f-met-leu-phe, (10( 9) M) while medium from unexposed corneas and exposed medium alone had less than 3% activity. An in vivo assay using sub-epidermal injection into the back of a rabbit gave qualitatively similar results, only f-met-leu-phe and the medium from irradiated corneas causing neutrophil infiltration of the tissue. A checkerboard analysis confirmed that the activity was chemotactic rather than chemokinetic. Release of a chemotactic factor following UV-B irradiation provides a mechanism for the recruitment of neutrophils, at specific localized areas of the endothelium, that is seen after discrete in vivo irradiation. The results also confirm the importance of corneal inflammatory mediators in the development of tissue damage subsequent to exposure to toxic agents. PMID- 2209065 TI - Clearance rate of macrophages from the vitreous in rabbits. AB - Macrophages are usually present in epiretinal membranes from eyes with proliferative vitreoretinopathy (PVR). Information on the kinetics of macrophages in the eye may be of help in identifying their role in this disease. To determine the half-life of macrophages in the vitreous, peritoneal macrophages were labeled by allowing them to phagocytose 141Cerium (gamma-emitter) labeled microspheres, and were then injected into the vitreous of the same rabbit from which they were obtained. The animals were sacrificed at various times post-injection and the radioactivity remaining in the vitreous was measured. Using this procedure, the half-life was found to be 4.8 days. PMID- 2209066 TI - Lectin binding of the interphotoreceptor matrix during retinal development in normal and RCS rats. AB - The retinas of both normal and Royal College of Surgeons (RCS) rats with inherited retinal dystrophy have been examined using lectin histochemistry to determine the developmental and degenerative changes of the glycoconjugates in the interphotoreceptor matrix (IPM) between postnatal day (P) 10 and P25, when the adult lectin binding patterns are seen in normal rats. Wheat germ agglutinin (WGA; recognizing sialic acid and/or N-acetyl-D-glucosamine) bound to the apical surface of the retinal pigment epithelium (RPE) sparsely at P10 and prominently at P12 in both strains. In both strains at P14, WGA also stained the basal outer segment zone at the inner segment-outer segment junction. Between P14 and P16 in both strains, there was a dramatic increase in the binding of the interstitial region, the space alongside the outer segments and between the apical and basal outer segment zones. The binding pattern of WGA in normal rats remained basically unchanged from P16 to P25, although the intensity of binding was increased somewhat. Ricinus communis agglutinin-1 (RCA-1; specific for galactosyl residues) bound to the outer segment zone prominently and diffusely with increasing intensity with age at P10, P12 and P14 in both strains. At P16 and older, the intense binding of the interstitial zone was dramatically reduced and the RCA-1 bound primarily to the inner and outer segment junctional region, with weak binding to the apical surface of the RPE in both strains. At P25, the binding of the inner and outer segment junctional region was even more restricted, limited to punctate sites in this zone in normal rats and almost missing in RCS rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2209067 TI - Proton NMR relaxation in hydrogel contact lenses: correlation with in vivo lens dehydration data. AB - A study of hydrogel contact lenses was undertaken to determine whether NMR relaxation data can be used as a predictor for on-eye lens dehydration. Proton NMR relaxation times (T1 and T2), were determined for a series of contact lenses for which on-eye dehydration data were also available. NMR relaxation times were found to depend upon lens water content, but the dependence was not monotonic. T1 values varied between 100 and 800 msec, and T2 values varied between 6 and 85 msec for the lenses studied. In this study, the NMR signal and corresponding relaxation times are average values, derived both from lens water protons as well as from exchangeable polymer protons. A simple analysis of the data indicates that the mobility of these protons varies by more than a factor of 10 for the lenses studied. A test for linear correlation between NMR relaxation rate, 1/T1 and relative change in lens water mass, % delta mw gave r = -0.830 for all data, and r = 0.904 if one lens was excluded. PMID- 2209069 TI - Congenital urinary tract abnormalities: prenatal and neonatal diagnosis. PMID- 2209068 TI - Pediatric pain: current status and new directions. PMID- 2209070 TI - Extracorporeal life support for cardiopulmonary failure. PMID- 2209071 TI - Biliary lithotripsy. PMID- 2209072 TI - "Status cosmeticus": a cosmetic intolerance syndrome. PMID- 2209073 TI - Thallium poisoning. PMID- 2209074 TI - Recent developments in sexually transmitted diseases: is heterosexual transmission of human immunodeficiency virus a major epidemiologic factor in the spread of acquired immunodeficiency syndrome? II: The United States and western Europe. PMID- 2209075 TI - Periungual fibroma. AB - Periungual fibromas are rare benign dermatologic lesions that may be acquired or associated with tuberous sclerosis or von Recklinghausen's disease. Periungual fibromas may place excessive pressure on the nail matrix, resulting in the potential for extensive nail pathologic conditions and pain. Radical surgical excision of the lesion is the preferred treatment in symptomatic cases. The case of such a foot lesion occurring in an elderly man, including histopathologic analysis of the excised lesion, is detailed here. PMID- 2209076 TI - Aggressive digital papillary adenoma: a case report. AB - Aggressive digital papillary adenoma has only been identified as an entity within the past six years. Only forty patients have been reported in the literature with this lesion. The lesion is found three times more commonly on the hands than on the feet. The lesion typically enlarges slowly and is asymptomatic. Patients in half of the reported cases have experienced local recurrence after initial removal. The authors present a case of aggressive digital papillary adenoma of the foot. PMID- 2209077 TI - The diabetic foot with synovial cyst. AB - Diabetic lower extremity infections, frequently polymicrobial, are at times fascinating though frustrating for the practitioner to treat. The classical triad of neuropathy, infection, and angiopathy is the hallmark of diabetic foot pathology. One of the main forms demonstrating the severe long-term neuropathic disease is called osteoarthropathy or Charcot joint. This is usually relatively painless, always progressive, and frequently destructive. It generally attacks the midtarsal joint and eventually changes the entire architecture of the foot, causing the so-called "rocker bottom" foot type. We present a case of a severely destructive Charcot foot that caused a large synovial cyst because of its vast underlying osseous pathology. The morbidity and mortality of these infections can be minimized by understanding the unique challenges these individuals offer the practitioner. PMID- 2209078 TI - Blunt dissection for the treatment of plantar verrucae. AB - The treatment of plantar verrucae has always been a challenging and perplexing problem to physicians. Due to the inherent nature of verrucae, response to various forms of treatment has been extremely unpredictable. It is believed that hyperhidrosis and abnormal pressure to the plantar aspects of the feet are contributing factors predisposing one to developing verrucae. This article describes a painless and effective approach to the treatment of plantar verruca through the use of blunt dissection. Following anesthesia obtained with a posterior tibial nerve block, the plantar verruca can be successfully dissected with an 80 percent cure rate. PMID- 2209079 TI - Study of efficacy of urea compound versus emollient cream in avulsive therapy of dystrophic nails. AB - The efficacy of commercially available urea compound was evaluated in twenty dystrophic nails in ten matched pairs of patients and compared to an emollient cream used under an occlusive dressing for seven days. The results of the study indicate no significant differences between the two treatment modalities. Both procedures provided excellent avulsion of dystrophic nails. PMID- 2209080 TI - Mucinous pseudocysts of the toes: an effective surgical method of treatment. AB - Mucinous pseudocysts are dome-shaped, fluctuant lesions that may affect the dorsal aspects of the toes. Although synovial involvement cannot usually be demonstrated by histologic examination of biopsy specimens, joint involvement is a causative factor. Arthroplasty of the intermediate phalangeal head is advocated along with excision of the pseudocyst and its underlying pedicle. Conservative approaches rarely provide a permanent cure for mucinous pseudocysts of the toes. PMID- 2209081 TI - Sister chromatid exchange and chromosome aberrations induced by curcumin and tartrazine on mammalian cells in vivo. AB - Sister chromatid exchanges (SCEs) and chromosomal aberrations induced by curcumin (a natural dye) and tartrazine (a synthetic dye) were studied on bone marrow cells of mice and rats following acute and chronic exposure via the diet. Except for two low concentrations in the curcumin and one low concentration in the tartrazine treated series a significant increase in SCEs was observed in all the concentrations of the two dyes tested. Except for two high concentrations during the 9 months treatment no significant increase in chromosomal aberrations was observed in the curcumin treated series, whereas tartrazine showed a significant increase in chromosomal aberrations in some of the higher concentrations in all the series tested. The results indicate that tartrazine is more clastogenic than curcumin. PMID- 2209082 TI - In situ nick translation of human chromosomes using Alu I: unmasking of recognition sites by proteinase K pretreatment. AB - Human chromosomes prepared according to routine methods were treated with the restriction endonuclease Alu I followed by staining with Giemsa solution or fluorescent dyes. This procedure results in a C-band-like appearance of the chromosomes due to removal of DNA from euchromatic chromosomal regions. The resistance of heterochromatic regions against cleavage by the enzyme has mainly been interpreted by the absence or rareness of recognition sites for this particular enzyme in these regions. Proteinase K pretreatment followed by a nick translation procedure with Alu I was combined to check this hypothesis. The results show that heterochromatic chromosomal regions can also be labelled. Thus, they are not characterized by a lack of recognition sites. Gradual deproteinisation of chromosomes changes the labelling pattern from a reverse C banding pattern to a C-band-like appearance. The resistance of heterochromatic chromosomal parts revealed by the technique is mainly due to local chromatin configuration rather than to the underlying DNA sequence itself. PMID- 2209083 TI - Correlation between meiotic behavior and breakpoints with respect to G-bands in two X-4 mouse translocations: T(X;4)7R1 and T(X;4)8R1. AB - The meiotic synaptic behavior of male mice heterozygous for one of two X-4 translocations was examined to test a recently advanced hypothesis (Ashley, 1988) suggesting that it is possible to predict the synaptic behavior (nonhomologous vs. homologous) and recombinational parameters (suppression vs. nonsuppression of crossing-over) of a chromosome aberration from mitotic G-band breakpoint data. The hypothesis was based on prior observations of synaptic behavior in a series of X-autosome translocations in mice. The breakpoints of the translocation T(X;4)7R1 are both in G-light bands. As predicted by the hypothesis, synapsis was restricted to homology. In contrast, one breakpoint of the translocation T(X;4)8R1 lies in a "stippled" band of the standard diagrams of Nesbitt and Francke (1981). As predicted (Ashley, 1988), "stippled" bands are shown here to synapse nonhomologously, i.e., they behave as "G-dark." The linkage data, as they relate to the synaptic data and the predictions of the hypothesis, are also discussed. PMID- 2209084 TI - Axial shortening during pachynema unrelated to nonhomologous synapsis. AB - The pachytene behavior of chromosomes participating in quadrivalent formation in male mice heterozygous for T(X;4)7Rl or T(X;4)8Rl was analyzed in electron micrographs of microspread spermatocytes. In each population of nuclei from the translocation heterozygotes, the longest 4X axes were approximately the proportional length expected from the respective contributions of the 4 and the X estimated from breakpoint positions in mitotic chromosomes. However, the 4X axis of these translocation quadrivalents undergoes extensive shortening. In both R7 and R8 the shortest 4X axis observed in the population of nuclei was approximately the length of the normal 4 axis. This equalization of axial lengths suggests that there may be an interchromosomal interaction between synapsed chromosomes. In R8, axial shortening of the 4X occurs as pachynema progresses. In both translocations, shortening is accompanied by twisting of the 4X around the 4. Both axial shortening and twists are characteristics exhibited by chromosomal axes of unequal length as part of the meiotic phenomenon described as "synaptic adjustment" (Moses, 1977). Synaptic adjustment involves, in addition, nonhomologous synapsis, which is delayed until the latter part of pachynema. However, axial shortening in R7 and R8 is not accompanied by nonhomologous synapsis. In R7, nonhomologous synapsis does not occur; in R8, it is confined to quadrivalents in which the 4X axis is near its maximum length (i.e., early). This behavior suggests that axial shortening and nonhomologous synapsis during the progression of pachynema (previously considered collectively under the term "synaptic adjustment") are not necessarily coupled events. PMID- 2209085 TI - Sex-chromosome constitution of postimplantation tetraploid mouse embryos. AB - Tetraploid mouse embryos were produced at the two-cell stage by blastomere fusion induced by inactivated Sendai virus. The embryos were from chromosomally normal female mice that had been fertilised by homozygous Rb(1.3)1Bnr males carrying a pair of large metacentric marker chromosomes in their karyotype. These "reconstructed" one-cell tetraploid embryos were then transferred to the oviducts of pseudopregnant recipients, which were subsequently autopsied early on the 10th day of gestation. Two-cell stage embryos that did not undergo blastomere fusion after 4-5 h were transferred to a second group of recipients, which were also autopsied early on the 10th day of gestation. From a total of 153 tetraploid embryos transferred to females that subsequently became pregnant, 135 implanted. Sixty-eight implantation sites were found to contain resorptions, whereas 67 contained mostly headfold presomite-stage embryos. Four embryos possessed four to six pairs of somites. All 57 embryos that could be analysed cytogenetically were found to be tetraploid. G-banding analysis revealed that 30 of these embryos had an XXYY and 27 and XXXX sex-chromosome constitution. The presence of two marker chromosomes in all mitotic preparations from each of these tetraploid embryos confirmed that they had all been produced by duplication of their original XY or XX diploid chromosome constitution, respectively. The XXYY:XXXX sex ratio observed was not significantly different from unity. In the control series of transfers, all of the embryos recovered were at the forelimb bud stage and had a diploid chromosome constitution. The results reported here differ from human clinical findings, in which the XXYY:XXXX sex ratio of 120 human tetraploid spontaneous abortions recovered over the last 20 years is 45:75. Possible explanations for these differences are briefly discussed. PMID- 2209086 TI - The human tyrosine kinase gene (FER) maps to chromosome 5 and is deleted in myeloid leukemias with a del(5q). AB - A novel member of the SRC tyrosine kinase gene family was recently isolated and characterized (Hao et al., 1989). This FES/FPS-related gene, named FER, lacks the transmembrane and extracellular domains which characterize tyrosine kinases with receptor function. Expression of FER in a wide range of cell types indicates a general role in intracellular signalling or differentiation processes. We have now mapped FER to chromosome 5q14----q23 using in situ hybridization techniques and suggest a more precise location within bands 5q21----q22. This region lies adjacent to a complex domain of growth factors and receptors, many involved in regulation of haematopoiesis. FER maps within a critical segment frequently deleted from chromosome 5 in patients with acute myeloid leukemia or myelodysplastic syndromes and was shown to be deleted in two such patients. It also maps close to the familial polyposis coli locus at 5q22. PMID- 2209087 TI - Rapid identification of sex in birds by flow cytometry. AB - A rapid method to identify sex in birds is described. The method requires microliter volumes of blood, and, under appropriate conditions, results can be available within an hour of sample collection. Samples can be stored at 4 degrees C or -20 degrees C without sacrificing the ability to discriminate sex differences in DNA content. The assay will find utility in laboratory, field, and applied studies, in other classes of vertebrates, and in studies on the dynamics of genome size within and among populations. PMID- 2209088 TI - In situ random primer extension of metaphase chromosomes. AB - We have developed a technique of random primer extension of fixed chromosomes that is applicable to both mouse and man. Human chromosomes are not homogeneously labeled with this technique; those regions corresponding to R-bands appear to be more sensitive than those identified as G-bands, whereas centromeric regions are not labeled. These results not only corroborate specific structural differences between distinct regions of mammalian genomes but also open up the possibility of assays with specific primers to test whether primer extension is useful for the identification of genes and families of sequences on chromosomes. PMID- 2209089 TI - Stillborn triploid complex hybrid of lemurs (Eulemur macaco x E. coronatus). AB - The karyotype of a triploid lemur hybrid, issued from the backcross of an Eulemur macaco male with a female E. coronatus hybrid is reported. The differential negative effect of the multivalents on male and female fertility is discussed. PMID- 2209090 TI - In situ DNA sequence mapping with surface-spread mouse pachytene chromosomes. AB - Surface-spread pachytene chromosomes are several times the length of metaphase chromosomes and the decondensed chromatin loops are attached to a well-defined axis (Weith and Traut, 1980). This arrangement permits detailed DNA sequence localization by in situ hybridization. We show that two probes to low-frequency repeated sequences (20 to 50 copies) which locate the centromere proximal in the mouse X metaphase chromosome between bands A1 and A3 (Disteche et al., 1985) and which map 5.5 cM apart (Disteche et al., 1989), hybridize to two distinct chromatin regions 3 to 5 microns apart on a 25 microns long pachytene X chromosome core. PMID- 2209091 TI - Regional localisation of the Friedreich ataxia locus to human chromosome 9q13--- q21.1. AB - We have previously assigned the Friedreich ataxia locus (FRDA) to chromosome 9; the current maximal lod score between FRDA and MCT112 (D9S15) is greater than 50 at a recombination fraction of theta = 0. The physical assignment of the locus defined by MCT112, and hence FRDA, has not been determined, although linkage analysis of MCT112 with other chromosome 9 markers inferred a location close to the centromere. We have used in situ hybridisation with MCT112, a corresponding cosmid MJ1, and DR47 (D9S5), coupled with mapping studies on hybrid cell panels, to define more precisely the location of the disease locus. The in situ location of all three probes is 9q13----q21.1, distal to the variable heterochromatin region. Physical assignment of FRDA will allow us to identify hybrid cell lines containing the mutated gene. PMID- 2209092 TI - Four genes for the calpain family locate on four distinct human chromosomes. AB - Calcium dependent proteases (calpains, CAPNs, E.C.3.4.22.17) constitute a family of proteins which share a homologous cysteine-protease domain (large subunits, L1, L2, and L3) and an E-F hand Ca2(+)-binding domain (L1, L2, L3, and small subunit, S). We have mapped the genes for four calpain proteins (L1, L2, L3, and S) on four distinct human chromosomes by a combination of spot-blot hybridization to flow-sorted chromosomes and Southern hybridization of DNAs from a human x mouse hybrid cell panel. The genes for calpain L1 (CAPN1, large subunit of calpain I), L2 (CAPN2, large subunit of calpain II), L3 (CAPN3, a protein related to the large subunits), and S (CAPN4, a small subunit common to calpains I and II) were assigned to human chromosomes 11, 1, 15, and 19, respectively. PMID- 2209094 TI - Assignment of the gene for beta-spectrin (SPTB) to chromosome 14q23----q24.2 by in situ hybridization. AB - Type I hereditary spherocytosis results from a molecular defect in the beta polypeptide of the erythrocyte cytoskeletal protein spectrin. Using a cDNA probe, we had previously assigned the gene for human erythrocyte beta-spectrin (SPTB) to chromosome 14 based upon analysis of its segregation in panels of human x rodent somatic cell hybrids (Winkelmann et al., 1988). Here we report the regional localization of this gene by in situ hybridization to 14q23----q24.2. PMID- 2209093 TI - Localization of the human T lymphocyte activation gene 519 (D2S69E) to chromosome 2p12----q11. AB - In situ hybridization was used to localize the lymphocyte activation gene 519 (D2S69E) on human metaphase chromosomes. A significant proportion of the grains were situated over chromosome 2p12----q11, a region which contains other genes involved in immunologic functions. PMID- 2209095 TI - Nutritional aspects of dysphagia. PMID- 2209096 TI - Nutritional assessment and requirements. AB - Nutrition plays an important role in health and disease, both in prevention and treatment. Increasing emphasis is being placed upon nutrition as a therapeutic tool to decrease the morbidity and mortality associated with obesity, hypertension, coronary artery disease, and cancer. Adequate nutrition should be a concern for all health care workers because of its impact on the overall health of patients. Health care professionals should be familiar with the essentials of nutritional assessment and basic nutritional requirements and be able to improve their patients' care in the face of nutritional deficiencies or excesses. PMID- 2209097 TI - Nutrition and the older adult. AB - The surge in interest in aging research has led to a growing awareness of the importance of adequate nutritional status in the elderly. This paper highlights the current state of our knowledge of nutrition in the older adult with regard to age-related alterations in nutritional status, the effects of altered nutritional status on the general well-being of the elderly, and the contributions of alcohol and drugs to altered nutritional status. Nutritional assessment techniques used for the elderly and directions for future research are discussed. PMID- 2209098 TI - The Exeter Dysphagia Assessment Technique. AB - The Exeter Dysphagia Assessment Technique (EDAT) uses noninvasive equipment to record, simultaneously, "feeding respiratory patterns," the time drink entered the mouth, and associated swallow sounds during feeding. The easily portable equipment enabled patients' swallowing ability to be tested, at the bedside if necessary, using a small amount of fruit-flavored drink. The results appear in chart form. EDAT findings from groups of normal subjects aged 2-90 years were compared with those from patients with dysphagia of neurologic origin and normal subjects under experimental feeding conditions. The results revealed maturation of the feeding respiratory pattern in the teenage years and remarkable consistency thereafter. Differences in the recordings between the normal and abnormal subjects were sufficiently marked to allow the findings to be used in the diagnosis of other patients with dysphagia of doubtful neurologic cause. Interpretation of the charts and recorded timings of the oral and pharyngeal stages of swallowing permitted a more accurate identification of sensory nerve, motor nerve, and functional involvement causing dysphagia of neurologic origin and may be used as a guide to the origin of the sensory deficit. PMID- 2209100 TI - Third Symposium on Dysphagia. March 22-23, 1990. Abstracts. PMID- 2209099 TI - Test-retest variability in normal swallowing. AB - The test-retest variability of the modified barium swallow study using videofluoroscopy was analyzed. Sixteen normal subjects (8 men, 8 women) were organized into 2 age groups: middle-aged group (mean, 45 years) and old-age group (mean, 66 years). Nine durational measures of the swallow were evaluated. There were no statistically significant differences for any of the measures between the initial test and a retest conducted days later. The findings suggest that, on the whole, normal subjects perform similarly on test and a retest. However, the variability displayed by these normal subjects may be clinically significant, indicating that test-retest swallowing duration measures require careful interpretation. PMID- 2209102 TI - Overview of geriatric nutrition. AB - Restoration and maintenance of optimal nutritional status in the long-term care setting may enhance the quality of life for geriatric patients. The elderly are at increased risk for poor nutrition due to age-related physiological and psychosocial changes, as well as the added toll of chronic disease. All of these may have a negative impact on adequate food intake. Health care providers must identify and address nutrition-related problems in a timely manner to correct nutrient imbalances and restore nutritional well-being in this population. PMID- 2209101 TI - Aspiration and the elderly. AB - Aspiration is prevalent in the elderly but its association with impairment of oral intake and gastroesophageal reflux is often misunderstood. This paper describes the causes, pathophysiology, and consequences of aspiration and their unique features in aged persons. It also explains how videofluoroscopic evaluation can assess current function while limiting factors that result in misinformation. The management of aspiration is discussed, emphasizing the importance and difficulties in maintaining functional well-being and possible complications of therapy. PMID- 2209103 TI - Nature, nurture, nutrition: interdisciplinary programs to address the prevention of malnutrition and dehydration. AB - Malnutrition and dehydration are common problems in nursing home patients. One explanation for this may be the large number of patients requiring feeding assistance. The Dysphagia Team at the Department of Veterans Affairs Medical Center in Miami, Florida served as the primary source in the expansion of a nutritionally supportive environment to assist in the prevention of malnutrition and dehydration in patients with feeding/swallowing disorders. "Silver Spoons," a program in which volunteers provide supervised feeding, "Happy Hour," a time each day during which an atmosphere is provided that encourages socialization and hydration, and "Second Seating," during which lunch is provided for patients who require modification of eating style, food texture, or timing are described. Analysis of the program's outcomes show it to be timely, pleasing to patients, and cost-effective. PMID- 2209104 TI - ACCP guidelines for an expert witness. PMID- 2209105 TI - Medical-legal definition of occupational asthma. PMID- 2209106 TI - Intrapericardial extralobar pulmonary sequestration in a neonate. AB - A huge pericardial effusion was diagnosed during fetal ultrasound examination performed in the 42nd week of pregnancy on a healthy 25-year-old woman. Immediately after the birth, a two-dimensional echocardiogram confirmed this finding in the infant, and an intrapericardial kidney-shaped solid mass measuring 45 x 56 x 15 mm, completely surrounded by pericardial effusion, was visualized to the left part of the heart. The heart was normal. No signs of cardiac tamponade were seen. At the age of two days, the mass was surgically resected and the pericardial fluid evacuated. Microscopic examination revealed that the mass was formed totally of normal lung tissue surrounded by normal pleura. To the best of our knowledge, this is the first case of intrapericardial extralobar sequestration consisting of an accessory lung with completely normal lung tissue. PMID- 2209107 TI - Traumatic rupture of aorta. Diagnosis by Doppler echocardiography. AB - Traumatic rupture of aorta is a serious complication in accidents, mainly road accidents, with a high mortality unless an immediate diagnosis and surgical correction is made. A case of traumatic rupture of the aorta shown in the acute phase by Doppler-echocardiography is reported. This technique can be of great value in the study of patients with thoracic trauma who do not show clear signs of aortic rupture which require urgent aortography. PMID- 2209108 TI - Transient mitral regurgitation due to mitral valve prolapse accompanied by systolic anterior motion of the mitral valve. AB - A grade 4/6 systolic murmur, systolic anterior motion of the mitral valve (SAM), and severe mitral regurgitation (MR) documented by two-dimensional Doppler echocardiography developed suddenly on the structurally normal heart of a patient with idiopathic portal hypertension. The patient did not have signs of congestive heart failure and the aforementioned phenomenon disappeared completely when the patient was in hepatic failure. This could be explained by a change in circulating blood volume either by gastrointestinal hemorrhage or hepatic failure. PMID- 2209109 TI - The effect of prolonged hypothermia on cardiac function in a young patient with accidental hypothermia. AB - A 20-year-old man had accidental, prolonged, and severe hypothermia. Serial radionuclide ventriculography disclosed reduced myocardial contractility during hypothermia that resolved after warming. The effects of hypothermia on cardiac function are discussed. PMID- 2209110 TI - Mucoid impaction of upper lobe bronchi in the absence of proximal bronchiectasis. AB - Mucoid impaction is a complication of asthma and is frequently recurrent in patients with allergic bronchopulmonary aspergillosis (ABPA). This report describes a patient with asthma and recurrent bilateral well-circumscribed densities on chest roentgenogram in the absence of ABPA. Recognition of this clinical presentation may avoid the need for invasive diagnostic procedures or steroid therapy. PMID- 2209111 TI - Confluence of pulmonary veins simulating a pulmonary mass. AB - Confluence of the pulmonary veins commonly appears on the frontal view of the chest and generally is easily recognized as such. On plain film tomography, computerized tomography, and pulmonary angiography, the anatomy of convergence of pulmonary veins prior to common entry into the left atrium is clearly displayed. In this report, attention is called to the occasional appearance of confluence of the pulmonary veins on the lateral view of the chest as a clearly circumscribed round opacity mimicking a lung or mediastinal mass. PMID- 2209112 TI - Cyclosporine and chronic sarcoidosis. AB - Two patients with progressive sarcoidosis who had poor responses and side effects from corticosteroid therapy were treated with cyclosporine. Cyclosporine suppressed conventional markers of inflammation and there was clinical improvement in one patient, but the disease recurred when therapy was discontinued. The second patient who had diabetes mellitus developed unstable glucose metabolism when given cyclosporine. This unstable diabetes mellitus together with side effects of nausea and vomiting resulted in weight loss and inadequate serum therapeutic levels that was associated with a poor therapeutic response to the cyclosporine. The major side effects in both patients were headache and gastrointestinal symptoms, but there was no renal dysfunction. We conclude that while corticosteroids remain the mainstay of sarcoid therapy, when these drugs have not been successful for the skin manifestations of the disease, a trial of cyclosporine may be justified. PMID- 2209113 TI - Orthostatic hypotension following right ventricular myocardial infarction corrected with mineralocorticoid therapy. AB - Severe hypotension while standing became a problem in a patient after discharge from the hospital following right ventricular myocardial infarction. Hemodynamic studies showed that right ventricular systolic function did not maintain adequate left ventricular preload and that the patient did not compensate for cardiac dysfunction by increasing blood volume. Volume expansion by mineralocorticoid therapy corrected the orthostatic hypotension and ameliorated symptoms. Hypotension eventually resolved and therapy was stopped four months after the myocardial infarction. PMID- 2209115 TI - Florid pulmonary veno-occlusive disease. AB - A young woman presented with rapidly progressive dyspnea and clinical findings strongly suggestive of primary pulmonary hypertension or possible pulmonary embolism (or both). She died of acute right-sided heart failure. A diagnosis of pulmonary veno-occlusive disease was made at autopsy. Approximately 100 cases of this disease have been reported previously in the literature. We describe a patient with a particularly florid progression of this unusual disease. Death occurred within six weeks of the onset of symptoms. PMID- 2209114 TI - Resolution of the adult respiratory distress syndrome following colectomy and liver transplantation. AB - A 32-year-old woman with liver failure from end-stage cirrhosis and ulcerative colitis developed septicemia and severe ARDS. Subtotal colectomy and a successful liver transplantation resulted in complete resolution of the ARDS. PMID- 2209116 TI - Triple-lumen central venous access via the external jugular vein. PMID- 2209117 TI - Pneumocephalus in association with lumbar punctures. PMID- 2209118 TI - Gemfibrozil interaction with warfarin sodium (coumadin) PMID- 2209119 TI - Pulmonary hypertension and sickle hemoglobinopathy. PMID- 2209121 TI - Phrenic nerve involvement in Charcot-Marie-Tooth disease. PMID- 2209122 TI - Lymphangiomyomatosis. PMID- 2209120 TI - Pleural and lung cryobiopsies. PMID- 2209123 TI - Testing for pulmonary embolism. PMID- 2209124 TI - Pulmonary alveolar phospholipoproteinosis associated with amyloidosis. PMID- 2209125 TI - American College of Chest Physicians' Consensus Panel on Hypertensive Emergencies. PMID- 2209126 TI - ACCP statement on the expert witness. PMID- 2209127 TI - Mixed venous saturation. The puzzle is still incomplete. PMID- 2209128 TI - Vasoconstrictors during CPR. Are they used optimally? PMID- 2209129 TI - Effect of internal mammary arterial mobilization on sternal blood flow. PMID- 2209131 TI - Ambulatory oxygen. The standard of care. PMID- 2209130 TI - Recidivism revisited. A case for steroids in relapsing COPD? PMID- 2209132 TI - Importance of verbal communication for the ventilator-dependent patient. PMID- 2209133 TI - Pulmonary alveolar proteinosis associated with Pneumocystis carinii. Ultrastructural identification in bronchoalveolar lavage in AIDS and immunocompromised non-AIDS patients. AB - Pneumocystis carinii (PC) has been recognized as frequently responsible for most opportunistic pulmonary infections occurring in immunocompromised AIDS and non AIDS patients. Moreover, these patients can be considered at risk for secondary pulmonary alveolar proteinosis. Therefore, we have investigated the occurrence of associated secondary alveolar proteinosis and PC pneumonitis in AIDS and non-AIDS immunocompromised patients. In a series of 26 bronchoalveolar lavages (BAL) in patients with PC pneumonitis (19 AIDS and seven non-AIDS patients), we observed on light microscopy, in addition to the honeycombed material, areas of an extracellular material that had a different pattern which was suggestive of that described in alveolar proteinosis. A systematic ultrastructural study of these 26 BAL fluid samples demonstrated in each of them an accumulation of phospholipid surfactantlike extracellular material mixed or not with the PC cysts. In nine cases, the observation of lipoproteinaceous material on light microscopy and abundant phospholipid material with myelinlike and myelin tubular laminated structures on electron microscopy was highly suggestive of an associated pulmonary alveolar proteinosis (PAP). Such an accumulation of extracellular material was not observed in the 11 BAL fluid samples collected in immunocompromised patients (seven AIDS and four non-AIDS patients) without PC pneumonitis. These findings demonstrated a particular frequency of associated PAP with PC pneumonitis. These results raise important questions concerning (1) the consequence of such an alveolar accumulation of lipoproteinaceous material on the clinical status and prognosis of the pneumonitis, and (2) the mechanisms responsible for this accumulation. PMID- 2209134 TI - Esophageal contribution to chest pain in patients with coronary artery disease. AB - We conducted a prospective study to determine the role of the esophagus in causing chest pain in patients with established CAD on optimum therapy. Thirty two men with documented CAD who complained of frequent and usually daily retrosternal chest pain were evaluated. Following a standard esophageal manometry and acid perfusion test, simultaneous two-channel ambulatory Holter monitor and esophageal pH record tests were performed for 24 hours. Fifty-three episodes of chest pain were documented in 20 patients; 11 patients were free of pain. Of the 20 patients who complained of chest pains, 17 (85 percent) demonstrated at least one episode of PPR, defined as a drop in distal esophageal pH to less than 4 within ten minutes before or after the onset chest pain. Episodes of asymptomatic GER were common. The correlation of PPR with chest pain was 70 percent (37/53 episodes) and of ischemic ECG changes with chest pain 13 percent (7/53); in the remaining, there was no correlation with either. Two patients demonstrated simultaneous PPR and ischemic ECG changes. Seventeen esophageal motility abnormalities were observed in 14 patients (45 percent). It is our conclusion that esophageal disorders contribute to chest pain in patients with documented CAD. In this group, GER plays a greater role than in those with normal coronary arteries. In addition, esophageal motility disorders are common in these patients. Esophageal testing can be undertaken safely in these patients. PMID- 2209135 TI - Hypokalemic and ECG sequelae of combined beta-agonist/diuretic therapy. Protection by conventional doses of spironolactone but not triamterene. AB - Salbutamol (Albuterol) and diuretics are commonly prescribed together in patients with airflow obstruction and are associated with electrocardiographic effects. We have now investigated whether the use of potassium-sparing drugs might prevent the ECG sequelae of such combined therapy. Ten healthy subjects received seven days of randomized treatments with: placebo, bendrofluazide (5 mg), bendrofluazide plus triamterene 50 mg (conventional dose), or triamterene 200 mg (high dose), and bendrofluazide plus spironolactone (100 mg). Potassium and ECG responses to inhaled salbutamol, 2 mg, were measured after each treatment period. The T-wave flattening in response to bendrofluazide and salbutamol (0.24[CI, 0.19 to 0.29]mV) was attenuated by the addition of triamterene, 200 mg (0.33[CI, 0.28 to 0.37]mV; p less than 0.05) and spironolactone 100 mg (0.42[CI, 0.37 to 0.47]mV; p less than 0.01), but not by triamterene 50 mg (0.25[CI, 0.20 to 0.30]mV). Spironolactone and high dose triamterene also diminished the frequency of U waves and ST depression. The ECG effects mirrored hypokalemic responses which were also blunted by high dose (p less than 0.01) but not low dose triamterene, as well as by spironolactone (p less than 0.001). Thus, the use of high dose triamterene and spironolactone protected against the hypokalemic and ECG sequelae of combined beta-agonist/diuretic therapy, whereas a conventional dose of triamterene had no effect. These findings may be important in the prevention of a potentially dangerous interaction in susceptible patients taking this combination of drugs. PMID- 2209136 TI - Ventilatory and diffusion abnormalities in potential heart transplant recipients. AB - Few data are available concerning pulmonary function in patients with severe chronic congestive heart failure. Of 315 patients evaluated for potential cardiac transplantation at UCLA, 132 underwent pulmonary function tests. The latter patients had severe heart failure with a mean left ventricular ejection fraction of 19 percent and mean cardiac index of 2.1 L/min/m2. Diffusion impairment either alone or combined with restrictive and/or obstructive ventilatory defects occurred in 67 percent of the patients evaluated. Diffusion impairment occurred as the sole abnormality in 31 percent of the patients and in combination with a restrictive ventilatory defect in 21 percent. A reduction in diffusing capacity has not been previously described as a frequent finding in patients with chronic congestive heart failure. In contrast to other studies involving patients with acute heart failure, obstructive ventilatory defects were uncommon. None of the lung function abnormalities was associated with smoking status, prior drug use, chest roentgenographic changes, hemodynamic findings, or clinical features, including duration of congestive heart failure. The mechanism for the diffusion impairment is unclear but could be due to chronic passive congestion with pulmonary fibrosis and/or recurrent pulmonary emboli. Recognition of diffusion impairment as a common finding in patients with severe chronic congestive heart failure who are candidates for heart transplantation is important for proper interpretation of possible post-transplant changes in diffusing capacity due to other causes. PMID- 2209137 TI - Characteristics and correlates of asthma in a university clinic population. AB - To contribute more comprehensive information about the characteristics of asthma, this article analyzed patients served by the University of Alabama at Birmingham Comprehensive Asthma Program. Their physicians rated one fifth of these patients as having "severe" asthma with the remainder about equally divided between "moderate" and "mild". One in two first received a diagnosis of asthma ten or more years previously. Common comorbidities were hypertension, obesity, rhinitis, bronchitis, sinusitis, and arthritis. One half had visited an emergency room or been hospitalized for asthma in the past year. Inhaled bronchodilators and continuous theophylline were the most commonly prescribed medications. Side effects, especially tachycardia and insomnia, were common and almost exclusively associated with theophylline or corticosteroid therapy. Spirometric assessment showed chronic airflow obstruction in those with more severe asthma. Prevalence of respiratory symptoms, intensity of medication regimen, incidence of side effects, and health care utilization increased as asthma severity increased. PMID- 2209138 TI - Differential therapy with calcium antagonists in pulmonary hypertension secondary to COPD. Hemodynamic effects of nifedipine, diltiazem, and verapamil. AB - In 53 patients with COPD and precapillary pulmonary hypertension, we investigated the effect of three typical calcium antagonists on hemodynamics at rest and during bicycle ergometer exercise. In the responders, the decrease in pulmonary vascular resistance following nifedipine was 23 percent at rest (p less than 0.0005) and 35 percent during exercise (p less than 0.0005); following diltiazem, it was 10 percent at rest (p less than 0.05) and 23 percent during exercise (p less than 0.025); following verapamil, it was 22 percent at rest (p less than 0.005) and 11 percent during exercise (p less than 0.025). The cardiac index rose significantly at rest and under exercise only after the administration of nifedipine (+16 percent and +8 percent, resp). Nifedipine caused the most distinctive peripheral vasodilation. The heart rate increased slightly following nifedipine and decreased slightly following diltiazem and verapamil. After long term therapy with nifedipine (13 +/- 5 months), the decrease in pulmonary artery pressure and pulmonary vascular resistance was no longer significant. In our opinion, the different hemodynamic action profiles will have consequences for the differential therapy in patients with COPD and pulmonary hypertension. PMID- 2209139 TI - Diagnostic value of nonfluoroscopic percutaneous lung needle aspiration in patients with pneumonia. AB - In forty-one patients (mean [+/- SD] age 51 +/- 19 years; range, 11 to 88 years; seven female and 34 male) with clinical signs and symptoms of pneumonia, we performed a nonfluoroscopic percutaneous lung needle (22 gauges) aspiration (PLNA) to investigate the diagnostic yield of this technique. All the patients were receiving antibiotics at the time of the study, and PLNA was performed either because of a lack of response to empiric antibiotic treatment or because of the severity of the pneumonia or the underlying condition of the patient. Eight patients were mechanically ventilated (MV) due to acute respiratory failure. The PLNA was performed at bedside and without fluoroscopic guidance. Twenty-two microorganisms were identified by means of stains and/or cultures of PLNA samples. Sensitivity of PLNA was 43 percent (18/41). We detected three false positive cultures probably due to contamination from the skin area punctured. In the eight MV patients studied, the sensitivity of PLNA was 37.5 percent, and the microbiologic findings turned out to be crucial for the outcome of the patients. Pneumothorax developed in three patients (7 percent) after PLNA. None of these three patients developed a pleural infection but two of them required thoracostomy drainage. None of the MV patients presented complications. Our results showed that nonfluoroscopic PLNA is a technique with moderately good sensitivity and with a low rate of false-positive cultures (8 percent) to diagnose pulmonary infections in patients with unresponsiveness to empiric antibiotic treatment or with severe pneumonia. Further evaluation of its diagnostic value and complications in MV patients is needed, although our preliminary results suggest that PLNA can be an alternative technique to other methods for diagnosing pulmonary infections in patients receiving artificial ventilatory support. PMID- 2209141 TI - Pulmonary function in commercial glass blowers. AB - This study examined the pulmonary function of 87 male commercial glass factory workers. Statistical analysis of the data indicated that workers with full-time glass blowing job descriptions had significantly higher percent predicted values for FVC, FEV1 and significantly higher maximal inspiratory and expiratory muscle pressures than their cohorts with minimal or nonglass blowing job descriptions. The results of this study indicate that persons using their respiratory muscles as full-time blowers to manufacture commercial blown glass products have significantly greater lung function values than part-time blowers or their nonglass blowing co-workers. PMID- 2209140 TI - Intravenous and oral corticosteroids for the prevention of relapse after treatment of decompensated COPD. Effect on patients with a history of multiple relapses. AB - To determine if a regimen of intravenous and oral corticosteroids reduces the relapse rate after treatment of decompensated COPD in the ED, 30 patients were studied. Forty-five visits in which intravenous and oral corticosteroids were given (T visits) were compared with an equal number of matched visits in which they were withheld (N visits). No differences were noted between T and N visits with respect to clinical findings, laboratory results and other forms of therapy. Treatment with corticosteroids reduced the relapse rate within 24 h of discharge. At 48 h, the cumulative relapse rate for T visits (8.9 percent) was significantly lower than for N visits (33.3 percent; p = 0.005). For patients with a history of multiple relapses, a regimen consisting of intravenous and oral corticosteroids reduces the risk of relapse after ED treatment of decompensated COPD. PMID- 2209142 TI - Severe aortic regurgitation as a late complication of temporal arteritis. AB - Two patients with a remote history of pathologically documented giant cell arteritis developed severe regurgitation. The first patient developed severe aortic regurgitation five years after the pathologic documentation of giant cell arteritis of the temporal arteries. Giant cell arteritis involvement of the aortic root was confirmed. The second patient developed aortic regurgitation seven years after pathologic documentation of giant cell arteries of the temporal arteries. Although pathologic confirmation of the aortic root process was not obtained, this case strengthens the clinical association between giant cell arteritis of the temporal arteries and subsequent aortic root dilatation and severe aortic regurgitation. Observation for signs of de novo severe aortic regurgitation is indicated in follow-up of patients with temporal arteritis. PMID- 2209143 TI - Lung sound nomenclature survey. AB - We report the terms used by 223 pulmonary physicians and 54 physicians in other specialties to describe eight recorded examples of lung sounds. The participants listened to the lung sounds at the 1988 American College of Chest Physicians annual convention and wrote "free form" answers. Pulmonary physicians used the terms "crackles" and "rales" with equal frequency to describe discontinuous adventitious lung sounds (ALS) and not at all to describe continuous ALS. Other physicians preferred the term "rales" in describing discontinuous ALS. The terms "wheeze" and "stridor" were used only in describing continuous ALS; however, the term "rhonchi" was frequently used to describe continuous and discontinuous ALS. The majority of participants recognized the normal breath sounds but not the pleural friction rub. Most did not use a qualifying adjective to describe ALS, and there was little agreement among those who did. The lung sound terminology used by physicians is not well standardized and the recommendations of the ATS/ACCP nomenclature subcommittee are not widely accepted. PMID- 2209144 TI - Predicting failure following shunting of pleural effusions. AB - We placed 43 shunts in 34 patients in five years. Twenty-four had malignant effusions and ten had benign effusions. Thirty-one patients had unilateral shunts, three had bilateral shunts and six required revisions for shunt failure. Two patients died after shunt placement from disease progression. Of the nine patients who experienced poor results, one was noncompliant in operating the shunt and eight had occluded shunts. In the 30 patients, who were compliant and had adequate length of follow-up, five had excellent results, 12 had good results, and five had fair results. Two of the patients with occluded shunts had good results after shunt revision; 24 patients had some symptomatic relief with shunting. Evaluation of factors including a history of prior abdominal surgery, performance status, and pleural fluid cell counts, differential, chemistries, and cytology revealed no significant differences between the patients who experienced shunt failure and those who had patent shunts. Shunting of pleural effusions is well tolerated and has good success rates in properly selected patients. PMID- 2209145 TI - Quality of life in elderly patients with chronic nonspecific lung disease seen in family practice. AB - We studied the quality of life of elderly patients with chronic nonspecific lung disease (CNSLD) in family practice. We also investigated the relationship between patients' somatic condition and their quality of life. Seventy patients, aged 40 years or older, with a diagnosis or symptoms of CNSLD completed the Sickness Impact Profile (SIP) and the list of daily activities (DAL). Pulmonary function (FEV1, IVC) and respiratory symptoms were assessed. The results indicated that patients were more impaired in their physical and psychosocial functioning than healthy control subjects. Most lung function parameters showed no correlation with the SIP scores. The respiratory symptoms of wheezing and dyspnea were related to patients' quality of life. Patients with chronic obstructive pulmonary disease (COPD) were more restricted in their daily functioning than patients with asthma. Since the relationship between patients' somatic condition and their quality of life is weak, we recommend comprehensive care that encompasses psychosocial as well as somatic interventions. PMID- 2209146 TI - The relationship of resting ventilation to mouth occlusion pressure. An index of resting respiratory function. AB - In order to examine the relationship of mouth occlusion pressure (MOP), an index of central inspiratory neuromuscular drive, to age and sex and to resting ventilation (VE), measurements were made in the seated posture in 84 healthy, normal subjects (38 men, 46 women; ages 18-72 years, mean +/- SD = 39.8 +/- 14.5 years) and in 79 patients with either airways obstruction (n = 63) or restrictive lung disease (n = 16). In the normal subjects, there was no significant relationship between age or sex and MOP (expressed as P0.1), which is the mouth pressure developed against a complete occlusion at 0.1 s after the beginning of inspiration, and dP/dtmax, the maximal rate of rise of this pressure; mean +/- SD for P0.1 = 0.75 +/- 0.32 cmH2O, and dP/dtmax = 19.41 +/- 10.10 cmH2O/s. Similarly, there was no significant relationship between age or sex and VE/P0.1 or VE/dP/dtmax. In 99 percent of normal subjects (83 of 84), VE/P0.1 was greater than 8.0 L/min/cmH2O, whereas in only 1 of the 79 patients was the value greater than 7.9 L/min/cmH2O. While the mean values of P0.1 and dP/dtmax were significantly different between normal subjects and patients, there was considerable overlap, whereas the ratio VE/P0.1 or VE/dP/dtmax provided excellent differentiation between normal subjects and patients with lung disease. This index, which is easily measured and requires minimal patient cooperation, provides valuable information in the clinical assessment of ventilatory drive and lung mechanics. PMID- 2209147 TI - Acute pulmonary effects of aerosolized pentamidine. A randomized controlled study. Toronto Aerosolized Pentamidine Study (TAPS) Group. AB - From June 1988 to February 1989, we enrolled 36 patients with human immunodeficiency virus into a randomized double-blind placebo-controlled trial assessing the efficacy and toxicity of aerosolized pentamidine (AP) as secondary prophylaxis for Pneumocystis carinii pneumonia. Each patient underwent spirometric evaluations before and after aerosolized treatment. There was no significant difference in the results of baseline pulmonary function tests between the two groups. Eleven patients (65 percent) in the AP group developed cough but only four demonstrated significant reduction in the forced expiratory flow rates after AP; four patients (21 percent) in the placebo group developed cough, but no significant change in the expiratory flow rates was noted. All bronchospastic episodes were self-limited and symptomatically responded to remedial inhaled albuterol (salbutamol) treatment. We conclude that AP treatment is frequently associated with coughing attacks (65 percent), but the actual incidence of bronchospasm on spirometry is much lower (24 percent) and is generally quite mild. PMID- 2209149 TI - Inhibition of natural killer cell activity by oral administration of theophylline. AB - Asthmatic patients have a low incidence of malignancies, and this is possibly due to higher NK cell activity in this population. Because theophylline is used widely in this population, we evaluated the influence of theophylline on NK cell activity in vitro and in vivo. The NK cell activity was significantly inhibited by direct addition of concentrations of aminophylline that exceeded 5 x 10(-5) M. To test whether such an effect can be observed in vivo, we administered one sustained-release tablet of theophylline (400 to 500 mg twice daily) to five normal volunteers for seven days. Significant inhibition of NK activity was noted after administration (mean percentage of inhibition, 41.3 percent), but the serum concentrations observed gave a mean value of 2 x 10(-5) M, which was lower than that yielding the same degree of inhibition by direct addition in vitro (about 20 x 10(-5) M). These results suggest that long-term theophylline therapy may inhibit NK cell activity, and thus more information would be needed to determine the position of such therapy in the management of asthmatic patients. PMID- 2209148 TI - Neutrophilia in bronchoalveolar lavage fluid of diffuse panbronchiolitis. AB - The clinical and pathologic features of diffuse panbronchiolitis (DPB) have been well reported to date, although its pathogenesis remains unknown. In the present study, we performed bronchoalveolar lavage (BAL) on three patients with biopsy specimen-proven DPB and eight patients with highly probable DPB (six women and five men; one smoker and ten nonsmokers), nine patients with chronic bronchitis (all men, five smokers and four nonsmokers), and nine normal control subjects (six women and three men, all nonsmokers) to clarify the cell populations in the lower respiratory tract. Neutrophils comprised 55.3 +/- 24.4 percent of recovered cells by BAL in DPB patients but only 6.6 +/- 6.4 percent in chronic bronchitis patients, and 1.8 +/- 1.5 percent in normal control subjects (p less than 0.001, all comparisons). The DPB patients also exhibited a decreased percentage of alveolar macrophages (34.9 +/- 23.5 percent) compared with chronic bronchitis patients and normal control subjects (p less than 0.001, all comparisons). The percentage of lymphocytes of the recovered lavage cells in DPB patients did not differ from that in chronic bronchitis patients and normal control subjects. These results indicate that neutrophils play an important role in the pathogenesis of DPB. They also suggest that neutrophilia of BAL-recovered fluid is a common finding in diseases associated with bronchiolar inflammation despite some clinical and pathophysiologic differences. PMID- 2209150 TI - Reactive airway dysfunction syndrome in three police officers following a roadside chemical spill. AB - The reactive airway dysfunction syndrome (RADS) is a recently described syndrome in which bronchial hyperreactivity and asthmatic symptoms develop in previously healthy individuals after a single large exposure to an irritating gas, fume, or vapor. We report a cluster of three Philadelphia police officers who developed RADS after a common exposure to toxic fumes from a roadside truck accident. Results of initial pulmonary function testing were normal in all three, and methacholine challenge was required for diagnosis in two out of the three. This syndrome needs to be recognized by physicians dealing with environmental or industrial medicine as a potential cause of loss of work or inability to perform on the job. Also, there is a potential for multiple individuals to develop this syndrome from a single incident. PMID- 2209151 TI - Pulmonary lipid peroxidation in cigarette smokers and lung cancer patients. AB - Lipid peroxidation (LPO) was studied in lung tissues of patients with lung cancer (LC, n = 37) or nonlung cancer (NLC, n = 13) and its relationships with the smoking habits and the degree of airway obstruction were investigated. Specimens of peripheral lung parenchyma, free of tumor tissue, were taken and the malondialdehyde (MDA) content was measured in the S-12 fractions. Airway obstruction was assessed by flow-volume curves, and data were expressed as percentage of the predicted values. Cigarettes smoked were expressed as pack years. The patients with LC and NLC did not differ by MDA content, age, and number of pack-years. On the contrary, FEF75-85 and MEF75 were significantly lower in LC than in NLC patients (p less than 0.05). The MDA content was inversely correlated to number of days patients had refrained from smoking (r = 0.66, p less than 0.001). The MDA content was higher in recent smokers (ie, people smoking during the last 30 days before surgery) than in the other patients (0.136 +/- 0.007 vs 0.116 +/- 0.007 mumol/g of tissue, p less than 0.05) and, by considering only recent smokers, MDA content was higher in LC patients (0.144 +/- 0.008 mumol/g of tissue) than in NLC patients (0.113 +/- 0.014 mmol/g tissue, p = 0.059). When patients were divided into "high MDA" and "low MDA" groups, MEF75 was much lower in the high MDA group (35.1 +/- 3.4 percent) than in the low MDA group (55.1 +/- 8.1 percent) (p less than 0.01). These results suggest the following: (1) enhanced level of prooxidant state in the lungs is associated with recent cigarette smoking; (2) LC patients may be more prone than respective NLC patients to oxidative stress; (3) MDA level and degree of small airway obstruction were associated and differed between LC and NLC patients even though these groups did not differ in the percentage of recent smokers; and (4) a common free-radical mediated pathway may be active for both LC and small airway obstruction. PMID- 2209152 TI - Effect of PAF-acether inhalation on nonspecific bronchial reactivity and adrenergic response in normal and asthmatic subjects. AB - Bronchial hyperreactivity, although recognized as a hallmark of asthma, is not totally understood. Mast cell-derived mediators, including histamine, have been shown to cause immediate bronchoconstriction, but until recently, no single mediator has been shown to induce prolonged changes in airway reactivity. Recent reports indicate PAF-acether (PAF) can induce increased nonspecific bronchial reactivity in normal subjects but not in asthmatics. We sought to elucidate the role of PAF in airway hyperreactivity by comparing the effect of inhaled PAF on methacholine and isoproterenol airway responsiveness in six nonasthmatic and six asthmatic subjects. Neither nonspecific airway reactivity nor isoproterenol responsiveness was changed following PAF inhalation in the nonasthmatic subjects in the six days following PAF. Asthmatics had increased airway responsiveness to methacholine at two hours post-PAF, which did not persist. Responsiveness to isoproterenol did not change in the asthmatic subjects. Additional evaluation of the role of PAF in causing changes in airway reactivity is warranted. PMID- 2209153 TI - Laryngomalacia in children. AB - Two hundred three (68 percent) of 297 children with laryngomalacia had associated respiratory disorders by flexible fiberoptic bronchoscopy (FFB). Associated disorders included congenital respiratory anomalies, a variety of anatomic obstructions of the upper and lower airways, and aspiration disorders. Mean age for isolated laryngomalacia (type 1) was 11.5 weeks (range, 5 weeks to 4 months) while children with laryngomalacia and associated respiratory disorders (type 2) had a mean age of 9.06 years (range, 6 weeks to 18 years). We conclude the following: (1) complete evaluation of the pediatric airways (bronchoscopy) is recommended in every symptomatic child with diagnosis of laryngomalacia confirmed by laryngoscopy; (2) type 1 laryngomalacia was more common in early infancy while type 2 laryngomalacia was associated with older age; (3) although type 2 laryngomalacia is the most common endoscopic diagnosis in our experience, the majority of cases were associated with lower airway dysfunction. PMID- 2209154 TI - Effects of epinephrine on hemodynamics and oxygen metabolism in dopamine resistant septic shock. AB - The hemodynamic effects of epinephrine were prospectively studied in 13 patients with septic shock who remained hypotensive after both fluid loading and dopamine. Hemodynamic measurements were performed before and one hour after the start of epinephrine infusion. Systolic, diastolic, and mean arterial pressure increased in all patients (p less than 0.01). Cardiac index and systemic vascular resistance increased by 34 and 32 percent, respectively (p less than 0.05), but heart rate and pulmonary vascular resistance remained unchanged. There was a concomitant increase in oxygen delivery (p less than 0.01) and oxygen consumption (p less than 0.05), the magnitude of the latter being related to baseline lactacidemia (p less than 0.01). In view of the generally recognized physiologic goals of septic shock management, we conclude that epinephrine could be an appropriate alternative where fluid loading and dopamine have failed. PMID- 2209155 TI - Three mixed venous saturation catheters in patients with circulatory shock and respiratory failure. AB - Thirty-one critically ill patients with acute respiratory failure and circulatory shock were divided into three groups. Group 1 included 11 patients with an inserted mixed venous saturation (SvO2) catheter using three-reference wavelengths and characterized by one transmitting and one detecting fiberoptic filament (Oximetrix opticath catheter); group 2 included eight patients with an inserted SvO2 catheter using two-reference wavelengths and characterized by one transmitting and one detecting fiberoptic filament; (Edwards sat-one catheter); group 3 included 12 patients with an inserted SvO2 catheter using two-reference wavelengths and characterized by one transmitting and two detecting fiberoptic filaments. Once calibration procedures were performed, SvO2 measured by the catheter and by an hemoximeter OSM 3 (reference value) were compared following each therapeutic intervention. Over a period of 1.5 to 6 hours during which the hematocrit value remained unchanged, 119 measurements were obtained in group 1, 91 in group 2 and 181 in group 3. The dispersion of SvO2 values was much more pronounced with the two-reference wavelength systems using either one or two detecting fiber optic filaments, and the correlation coefficient was significantly higher with the three-reference wavelength system (r = 0.970 for the Oximetrix catheter vs r = 0.855 for the Edwards catheter and r = 0.826 for the Spectramed catheter, p less than 0.001). After 24 hours, the spontaneous drifts in the two-reference wavelength systems, using either one or two detecting fiber optic filaments (expressed as the SvO2 value measured by the catheter minus the reference SvO2 value) were significantly higher than the spontaneous drift in the three-reference wavelength system (9.3 +/- 7 percent for the Edwards catheter and +/- 6 +/- 4.1 percent for the Spectramed catheter vs 3.3 +/- 3.1 percent for the Oximetrix catheter, p less than 0.05). This study shows that a three wavelength system is more accurate than a two-wavelength system for measuring acute changes in SvO2. The addition of a second detecting fiber optic filament does not seem to improve the accuracy of the system when SvO2 changes occur in conditions of stable hematocrit. PMID- 2209156 TI - Lactate levels as predictors of the relationship between oxygen delivery and consumption in ARDS. AB - We reviewed the changes in Do2 and Vo2 in 58 patients with ARDS after interventions which included fluid loading, blood transfusion, and PEEP. After a significant change in Do2, patients with lactic acidosis (lactate level greater than 2.4 mmol/L) exhibited significant corresponding changes in Vo2 (p less than 0.001); however, no change in Vo2 was observed in patients without lactic acidosis (1-beta greater than 0.8). We conclude that a biphasic pattern of oxygen utilization in patients with ARDS emerges when subsets of patients with and without lactic acidosis are compared. Lactic acidosis, a marker of anaerobic metabolism, may be a characteristic of patients with ARDS who exhibit changes in Vo2 that are dependent on changes in Do2. PMID- 2209157 TI - What is asbestosis? PMID- 2209158 TI - Pulmonary functional impairment associated with pleural asbestos disease. Circumscribed and diffuse thickening. AB - To define the pulmonary functional impairment associated with pleural asbestos signs (PAS), we compared 738 men with only circumscribed (plaques) or diffuse pleural thickening on chest roentgenograms but no irregular opacities by ILO pneumoconiosis criteria (1980) with 738 age-matched asbestos-exposed men without any roentgenographic signs and with 228 men unexposed to asbestos. All men were white. Spirometry and total thoracic gas volumes (TGV) were measured and expressed as percentage of predicted of white Michigan men who have been modeled for spirometric values thereby adjusting for height, age, and in current and ex smokers for duration of smoking. Asbestos-exposed men who never smoked had reduced FEF75-85 (p less than 0.01) and increased TGV (p less than .0001) as compared with unexposed men. The 155 men with PAS who had never smoked had reduced flows (p less than .0001), FVC (p less than 0.0056), and TGV (p less than .0001) when compared with 155 age-matched asbestos-exposed men. The 325 asbestos exposed current smokers with normal chest roentgenograms compared with unexposed smokers had reduced expiratory airflows (p less than 0.0001), reduced FEV1 (p less than 0.004), and increased TGV (p less than 0.0001). The 325 current smokers with PAS had additional air trapping that further reduced vital capacity. Thus, PAS were associated with significant pulmonary dysfunction in men who never smoked, and current and ex-smokers had additional dysfunction even after adjustment for duration of smoking. PMID- 2209159 TI - "Mechanical" causes of pulmonary edema. PMID- 2209160 TI - Cardiovascular drugs in the elderly. PMID- 2209161 TI - Air in the neck. PMID- 2209162 TI - Failure of lung repair following acute lung injury. Regulation of the fibroproliferative response (Part 2). PMID- 2209163 TI - Mechanical disruption of pulmonary emboli in dogs with a flexible rotating-tip catheter (Kensey catheter). AB - Pulmonary embolism was induced in 11 dogs by the injection of three- to four-day old allogeneic blood clots. The clots were made radiopaque by soaking them in contrast material. The resulting clots were firm, 3 to 4 cm long, and 1 cm in diameter. Injection of the clots into the external jugular vein consistently produced occlusion of at least one of the lobar pulmonary arteries. In every instance in which the tip of the catheter could be positioned at the clot embolus (six dogs), the clots were readily fragmented with a number 8 French (2.67 mm OD) flexible rotating tip catheter (Kensey catheter) activated at 80,000 rpm. Overall perfusion was shown by posttreatment angiograms to be markedly improved. These studies show that catheter-tip fragmentation of pulmonary emboli with a Kensey catheter has excellent potential for therapeutic application in patients with pulmonary embolism. PMID- 2209164 TI - The effects of methoxamine and epinephrine on survival and regional distribution of cardiac output in dogs with prolonged ventricular fibrillation. AB - This study compares the effects of methoxamine, a pure alpha 1-agonist, and epinephrine on cerebral and myocardial blood flow, central hemodynamics, and survival in a randomized placebo-controlled fashion during prolonged ventricular fibrillation (VF) in a canine model. Twenty-four anesthetized and ventilated adult mongrel dogs were instrumented for regional blood flow determinations using radio-labeled microspheres. The dogs were randomized to receive either 20 mg of methoxamine as a single intravenous bolus or repeated boluses of 0.02 mg/kg of epinephrine, 0.2 mg/kg of epinephrine, or normal saline solution placebo beginning at three minutes following induction of VF and initiation of closed chest cardiac massage (CCCM). Organ blood flow measurements were determined during normal sinus rhythm and after five and 20 minutes of VF. All six dogs receiving methoxamine were successfully resuscitated in contrast to only one in each of the epinephrine-treated groups and none of the dogs receiving placebo (p less than .01). Although epinephrine was associated with significantly higher blood pressures than placebo during cardiopulmonary resuscitation (CPR), blood pressures achieved with methoxamine were significantly higher than those observed in the other three treatment groups (p less than .001). Cerebral blood flow was significantly higher with both methoxamine and high-dose epinephrine (p less than .05). Mean left and right ventricular myocardial flows were highest with methoxamine but this did not achieve statistical significance. In contrast, organ flows measured in the animals receiving the lowest dose of epinephrine were not significantly higher than those associated with placebo. Cardiac output after 20 minutes of CPR was significantly lower with high-dose epinephrine than with methoxamine or placebo (p less than .05). Our results suggest that methoxamine significantly improves regional cerebral blood flow and survival during CPR and although high-dose epinephrine is associated with comparable improvements in regional cerebral blood flow, this treatment is associated with deterioration in central hemodynamics during prolonged VF and does not enhance survival. PMID- 2209165 TI - Penetration of aztreonam into pleural exudate following rapid intravenous bolus or constant infusion. AB - A study on the effects of the mode of administration on aztreonam (AZ) concentrations in pleural fluid was performed in human subjects. The same dose of AZ was given as an intravenous bolus injection to one group and as a drip infusion to another group of patients. Serum and pleural fluid samples were collected at different times after drug administration, and the antibiotic concentrations were measured by using a microbiological method. The highest serum and pleural exudate concentrations and area under the curve values were obtained after drip infusion. These results indicate that drip infusion gives higher concentrations of AZ in pleural effusion. PMID- 2209166 TI - Penetration of cefonicid into human lung tissue and lymph nodes. AB - The present study was undertaken in order to investigate the penetration of cefonicid, a long-acting parenteral cephalosporin, with enhanced activity against most gram-positive and gram-negative pathogens, into human lung tissue and lymph nodes in patients undergoing open thoracotomy. Samples of lung tissue, lymph nodes and serum were obtained at various times after a single intramuscular dose of 1 g. The concentration of cefonicid was assayed by an agar diffusion method with Bacillus subtilis used as the test organism. The mean concentrations of cefonicid in serum at 2, 4, 8, 12 and 24 h after the injection were 91.5, 66.1, 35.7, 21.8 and 2.9 micrograms/ml, respectively. The mean levels of cefonicid into the hilar lymph nodes at the same times were 22.3, 18.7, 12.0, 6.9 and 1.5 micrograms/ml, respectively, while its concentrations in lung tissue were lower than those in lung lymph nodes up to the 12th hour (12.1, 14.6, 7.8, 5.4 and 1.9 micrograms/ml, respectively). Our results show that cefonicid was well distributed in interstitial fluid from which pulmonary lymph is formed and that its concentrations in lung tissue and lymph nodes were sufficient to inhibit most pathogens involved in respiratory tract infections. This finding was considered important, because it demonstrated that the high binding by plasma protein of cefonicid did not prevent it from entering lung tissue and fluids in useful quantities. PMID- 2209167 TI - In vitro and in vivo effects of subinhibitory concentrations of clindamycin on experimental Klebsiella pneumoniae sepsis. AB - We studied the effect of subinhibitory doses of clindamycin on the course of experimental Klebsiella pneumoniae sepsis. Wistar rats were injected intraperitoneally with an inoculum containing 5 x 10(6) colony-forming units of K. pneumoniae resistant to clindamycin (minimum inhibitory concentration greater than 128 micrograms/ml) and then distributed to receive clindamycin 10 mg/kg/day or placebo for 10 days. All animals were bacteremic at 3 h. When the magnitude of bacteremia was compared, no difference was seen during the first 24 h; however, by 72 h the clindamycin-treated group had a significant decrease in the number of colony-forming units per milliliter blood (p less than 0.01). The mortality rate showed a tendency to decrease in the treated group (0%) as compared with the control group (30%). By 120 h, 3 of the 9 (33%) surviving animals from the control group were still bacteremic versus 0 of 11 (0%) in the clindamycin treated group. These results suggest that subinhibitory clindamycin therapy can improve bacterial clearance and survival during the course of experimental K. pneumoniae sepsis. PMID- 2209169 TI - In vitro activity of PD127,391, a new quinolone against bacterial isolates from cancer patients. AB - The in vitro activity of PD127,391, a new 4-quinolone, was compared to that of ciprofloxacin against common clinical bacterial isolates from patients with cancer. PD127,391 was found to have a broad antimicrobial spectrum with excellent activity against gram-positive isolates (including multidrug-resistant organism such as Corynebacterium jeikeium, Enterococcus faecalis, Enterococcus faecium, methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus spp.). It was also extremely active against gram-negative bacilli including Pseudomonas aeruginosa. Against organisms such as Achromobacter xylosoxidans, Acinetobacter spp. and Xanthomonas maltophilia, which are frequently resistant to a variety of antimicrobial agents, PD127,391 exhibited good activity, inhibiting all such isolates at a concentration of 0.5 micrograms/ml. Overall, PD127,391 was far more potent than ciprofloxacin against gram-positive isolates and slightly more active against gram-negative isolates. No bacterium that we examined needed more than 2 micrograms/ml of PD127,391 for inhibition. PMID- 2209168 TI - In vitro activity of temafloxacin hydrochloride (TA-167 or A-62254), a new fluorinated 4-quinolone. AB - The in vitro antibacterial activity of temafloxacin hydrochloride (TA-167 or A 62254) was evaluated against a wide variety of clinical isolates and compared with those of other fluoroquinolones. The potency (MIC90) of the compound against gram-positive aerobic bacteria was higher or comparable to those of ciprofloxacin, ofloxacin, and norfloxacin. Against most gram-negative enteric bacteria and Pseudomonas species, temafloxacin was less active than ciprofloxacin, but was generally as active as ofloxacin and norfloxacin, except against Proteus species and Morganella morganii. Against obligate anaerobes, it was more active than the reference quinolones. Temafloxacin was bactericidal for one strain each of Staphylococcus aureus. Escherichia coli, and Pseudomonas aeruginosa. The compound inhibited E. coli DNA gyrase activity at a low concentration. PMID- 2209170 TI - Adenosylmethionine decarboxylase inhibitors--lack of activity against cytopathic effects of HIV. AB - Many bis(amidinohydrazones) are potent inhibitors of adenosylmethionine decarboxylase (AdoMetDC), a key enzyme of polyamine biosynthesis, and some of them are also known to be powerful antiviral agents. Therefore, seven bis(amidinohydrazones), including the two most potent inhibitors of eukaryotic AdoMetDC so far reported, were screened for antiviral activity against the human immunodeficiency virus (HIV). The screening was performed by incubating susceptible human leukemia cells in microculture plates in the presence or absence of test compounds for 7 days and by determining the number of viable cells at the end of the test. None of the compounds screened, however, displayed any detectable antiviral activity (i.e. none of them increased the viability of virus-infected cells) in these tests whose aim was to reveal potential activity against the cytopathic effects of HIV. This result suggests that inhibitors of AdoMetDC, at least when used alone, are devoid of value for the prevention of the cytopathic effects of HIV. However, the possibility cannot be totally excluded that some of them might decrease the amount of infectious progeny viruses formed, just as methylglyoxal bis(amidinohydrazone) is known to do in the case of vaccinia virus. PMID- 2209171 TI - Influence of macrolide antibiotics on the chemiluminescence of zymosan-activated human neutrophils. AB - No statistically significant changes in the chemiluminescence response of the whole blood were noted following in vitro treatment with 0, 2, 10, 25, or 50 micrograms/ml of erythromycin, josamycin, miomycin, roxithromycin, and spiramycin. These results suggest that these macrolide antibiotics are unlikely to impair the phagocytizing abilities of human neutrophils, in agreement with previous findings indicating their lack of influence upon neutrophil chemotaxis. PMID- 2209172 TI - Head Start: 25 years building America's future. PMID- 2209173 TI - Improving the quality of life for youngsters with HIV. PMID- 2209174 TI - Development of knowledge about the role of inference in text comprehension. AB - The goal of this research was to learn when children recognize that they make inferences to understand text, and how this knowledge affects their ability to revise text and to monitor its informativeness. In 4 experiments, first-, second , and third-grade children (6-10 years) were presented with brief stories in which the physical cause of a target event was described explicitly, implied, or not mentioned in the text. In the first 3 experiments, children judged whether they had inferred the cause or if it had been explicitly mentioned in either the original or a revised version of the story. The results showed that for stories with implicit causes, first- and second-grade children tended to report that the causes had been explicitly mentioned, while third graders correctly reported that the causes were inferred. In the fourth experiment, children were asked to judge the difficulty of inferring the cause from problematic and ambiguous versions of the stories. Older children were more likely to report difficulties in inferring the target information. Third graders were also more likely to revise the texts to include additional information about the causes of the target events. The results show that younger children tend to attribute inferred information of the text, while older children clearly distinguish inferred and explicit text information. PMID- 2209175 TI - Just-world reasoning in children's immanent justice judgements. AB - The present study investigated the belief by Piaget that immanent justice responses occur when fairness judgments override conceptions of physical causality in young (6-8 years) children's understanding of a certain type of story. The structure of Piaget's stimulus stories was analyzed, and they were found to involve 3 narrative elements: motive valence, outcome valence, and causal connection. These 3 factors were crossed to create 8 types of stories, one of which (e.g., a character with a bad motive receives a negative outcome which is noncausally related to the previous motive) was the type used by Piaget. It was predicted that 2 types of stories would yield immanent justice responses: good motive/positive outcome/noncausal and bad motive/negative outcome/noncausal. Subjects received 4 stories and answered the Piagetian immanent justice questions and rated outcome fairness. Subjects were 48 each of children in grades 1, 3, and 5 and 38 college students. Results supported the prediction that children use the belief in a just world in immanent justice judgements. PMID- 2209176 TI - New evidence on the development of the word big. AB - Previous studies of children's understanding of big suggest a curvilinear trend. 3-year-olds, like adults, interpret big as referring to area, while 5-year-olds take big to mean tall. The results of 6 experiments indicate that the curvilinear trend is not obtained in all stimulus contexts. When objects vary extremely, younger and older children take big to mean tall. The object to which big is applied also influences whether height, length, or area is attended to. Moreover, in a production task, adults rarely used the work big to describe the stimuli with which children's understanding of big is typically tested. Taken together, the results suggest that the meaning and use of big is complex and that big may not at any age refer simply to the larger object. It is proposed that the meaning of big is a dynamic system driven by a multiple of perceptual, conceptual, and semantic influences. PMID- 2209177 TI - Mathematics achievement of children in China and the United States. AB - First and fifth graders in Beijing and Chicago were given a battery of mathematics test. Whether tested with problems requiring solely computation or with ones requiring application of knowledge about mathematics, American children's performance was consistently inferior to that of Chinese children. Interviews with American children suggested that they like mathematics, believe they are doing well in mathematics, and do not perceive mathematics as a difficult subject. American children's poor performance appears to be attributable, in part, to low motivation for devoting more attention to mathematics. Low standards held by American parents for academic achievement and lower interest in teaching mathematics by American teachers appear to contribute to American children's poor performance. PMID- 2209178 TI - The psychological functions of preadolescent peer activities. AB - The psychological functions of preadolescent peer activities were assessed by examining activity-related prescriptions and prescriptions for peer behavior. 91 fifth- and sixth-grade children (48 girls) kept week-long diaries of important peer activities and liked and disliked behaviors performed by peers in the activities. 81 other fifth- and sixth-grade children (40 girls) rated the importance and prevalence of each activity and indicated which of several positive and negative behaviors they would most like or dislike to happen in 10 of the activities. Results indicate that collectively, the activities sampled serve 3 main functions based on their prescriptive and prescriptive behavioral profiles: (a) they provide a context for sociability, enhancement of relationships, and a sense of belonging; (b) they promote concern for achievements and integrity of the self; and (c) they provide opportunities for instruction and learning. Not all activities serve all functions, however, and children may require exposure to a variety of activities to accrue a full range of psychological experiences. The findings also illustrate the potential importance of activity-related information for discerning the meaning and evaluating the effectiveness of social behavior. The advantages of the methodology are discussed. PMID- 2209179 TI - Having friends, keeping friends, making friends, and being liked by peers in the classroom: predictors of children's early school adjustment? AB - The potential role that children's classroom peer relations play in their school adjustment was investigated during the first 2 months of kindergarten and the remainder of the school year. Measures of 125 children's classroom peer relationships were obtained on 3 occasions: at school entrance, after 2 months of school, and at the end of the school year. Measures of school adjustment, including children's school perceptions, anxiety, avoidance, and performance, were obtained during the second and third assessment occasions. After controlling mental age, sex, and preschool experience, measures of children's classroom peer relationships were used to forecast later school adjustment. Results indicated that children with a larger number of classroom friends during school entrance developed more favorable school perceptions by the second month, and those who maintained these relationships liked school better as the year progressed. Making new friends in the classroom was associated with gains in school performance, and early peer rejection forecasted less favorable school perceptions, higher levels of school avoidance, and lower performance levels over the school year. PMID- 2209180 TI - Intimacy of friendship, interpersonal competence, and adjustment during preadolescence and adolescence. AB - This study examined the hypotheses that (a) intimacy of friendship is more integral to socioemotional adjustment during adolescence than preadolescence, and (b) that competence in close relationship skills is more important during adolescence than preadolescence. Subjects were 102 10-13-year-old preadolescents and 70 13-16-year-old adolescents. Self- and friend ratings of friendship intimacy were gathered using a 2-step procedure ensuring that students rated only reciprocated friendships. Self- and friend ratings of close relationship competence were gathered using the newly developed Adolescent Interpersonal Competence Questionnaire. Intimacy of friendship was consistently and moderately correlated with adjustment and competence among adolescents but less consistently related among preadolescents. Significant age differences in coefficients were predominantly found for correlates of self-reported rather than friend-reported intimacy. Overall, the findings support the view that the ability to establish close, intimate friendships becomes increasingly important during early adolescence. PMID- 2209182 TI - Self-predictions of emotional response patterns: age, sex, and situational determinants. AB - A total of 407 males and females in 4 different age groups (M age = 8.0, 10.8, 15.2, and 20.3 years) completed questionnaires requiring self-ratings of 5 emotions (angry, happy, sad, fearful, and loving), on a 5-point scale, for 10 affect-laden sentences. Each of the 5 emotions was targeted as a key emotion by 2 sentences. The resulting patterns indicate that children as young as 8 can discriminate between affect-eliciting statements, differentially rate up to 5 concurrent emotional responses, and predict response patterns similar to those predicted by adults. Furthermore, sex differences occur during adolescence whereby males predict more varied but less intense secondary emotions, whereas females predict fewer but more intense secondary emotions. PMID- 2209181 TI - A mediational model of the impact of marital conflict on adolescent adjustment in intact and divorced families: the role of disrupted parenting. AB - The present study was concerned with the development and testing of a structural equation model wherein the relation of interparental conflict to the adjustment problems of young adolescents is mediated through its impact on 3 aspects of parenting behavior: lax control, psychological control, and parental rejection/withdrawal. The model was tested separately on a sample of 46 young adolescents from intact families and a group of 51 adolescents from recently divorced families. The hypothesis that most of the relation between martial conflict and adolescent adjustment problems could be explained through perturbations in the parent-child relationship received considerable support; the only direct effect of conflict was on externalizing problems in the intact sample. The results also suggested that the mediational patterns were somewhat different for the 2 samples, and that the model accounts for a greater proportion of the variance in the adjustment problems of adolescents from intact homes than of those from recently divorced families. PMID- 2209183 TI - Changes in and stability of cardiovascular responses to behavioral stress: results from a four-year longitudinal study of children. AB - This study examined the changes in and stability of cardiovascular responses to behavioral stress among 132 children in a 4-year longitudinal study. Children's heart rate and blood pressure were measured at rest and while performing 3 tasks: serial subtraction, mirror image tracing, and isometric exercise. This procedure was followed at study entry when children were in grades 2-12 (ages 6-18 years) and at follow-up when children were in grades 6 through post-high school (ages 11 21 years). Results showed that blood pressure and heart rate responses during the tasks were reliable across time for all measures except heart rate responses during isometric exercise. Systolic blood pressure responses to all tasks increased with age for boys, but not for girls. These results support the notion that cardiovascular responses to behavioral stress are a stable individual difference variable. PMID- 2209184 TI - Emotional and behavioral predictors of preschool peer ratings. AB - It was predicted that social cognitive, behavioral, and affective aspects of young children's social development would predict stable peer ratings of their likability. Measures of likability, emotion knowledge, prosocial and aggressive behavior, peer competence, and expressed emotions (happy and angry) were obtained for 65 subjects (mean age = 44 months). Sociometric ratings, particularly negative, were stable over 1- and 9-month time periods. Correlational analyses showed that emotion knowledge and prosocial behavior were direct predictors of likability. Prosocial behavior mediated the relations of gender and expressed emotions with likability (i.e., gender and expressed emotions were each related to prosocial behavior, and prosocial behavior was related to likability, but neither gender nor expressed emotions were related to likability with prosocial behavior partialled out). Knowledge of emotional situations similarly mediated the age-likability relation. Results uphold the early development of stable peer reputations and the hypothesized centrality of emotion-related predictors of likability. PMID- 2209186 TI - Changes in cooperation and self-other differentiation during the second year. AB - Cooperation in peer interaction emerges during the second half of the second year. A consideration of the skills and knowledge entailed in these early forms of cooperation suggests that young children's emerging ability to differentiate self from other as causal agents may relate to their ability to coordinate behavior with age mates toward a common goal. Children at 12, 18, 24, and 30 months were observed in same-age, same-sex dyads (8 dyads per age) while attempting to solve a simple cooperation problem. They were also individually administered an elicited imitation task used to index decentration, or self-other differentiation. No 12-month-old dyad could cooperate, 18-month-olds did so infrequently and apparently accidentally, whereas 24- and 30-month-olds were able to coordinate behavior with one another quickly and effectively. Children who were better able to accommodate their behavior to one another during cooperation also represented the agency of others at a more advanced, decentered level. PMID- 2209187 TI - When infants look to their parents: I. Infants' social referencing of mothers compared to fathers. AB - 12-month-olds were seen with their mothers and fathers in a laboratory procedure designed to compare infants' solicitation of, emotional resonance to, and self regulation on the basis of happy, fearful, and conflicting emotional signals from mothers versus fathers. Measures of positive and negative affect and affect lability; of look, approach, and proximity behavior; and of overall response pattern were obtained. Infants showed more positive and less negative affect and greater toy proximity with happy compared to fearful signals. Few differences emerged in infants' referencing response to mothers versus fathers. Infants looked more to mothers than fathers when no signals were given but did not differentiate between parents when only one was signaling or when both were signaling (conflict). In affective state and behavioral regulation, they were not differentially responsive to maternal versus paternal signals either when only one parent was signaling or when both were giving signals. PMID- 2209185 TI - Inhibition: its stability and correlates in sixteen- to forty-month-old children. AB - Inhibition was assessed in 144 Swedish children when they averaged 16 months of age using a composite measure tapping sociability toward strange adults, noninvolvement in peer play, and parental ratings of fearfulness. 91 children entered out-of-home care within 2 weeks of these initial assessments. Children were observed in this setting playing with peers; teachers and parents also rated children's adjustment to the out-of-home care settings. 1 and 2 years later, the children were assessed again, both at home and in the alternative care settings. Results showed that individual differences in inhibition were stable over the 2 years of the study. Inhibited children engaged in less high-quality peer play both at home and in the alternative care settings, and they were less able to play alone in their mothers' absence. On contemporaneous but not subsequent ratings, inhibited children had more difficulty adjusting to out-of-home care. Inhibition was not itself affected by out-of-home care experiences, and there were no sex differences in inhibition. PMID- 2209188 TI - When infants look to their parents: II. Twelve-month-olds' response to conflicting parental emotional signals. AB - 12-months-olds were seen in a laboratory procedure in which they were given happy, fearful, and conflicting emotional signals by their mothers and fathers with reference to 5 unusual toy stimuli. Measures included: positive and negative affect, affect lability, and approach and proximity behavior toward the toy. Infants did not "select" a signal on the basis of a maternal or paternal primacy in emotional referencing, but responded to both signals and experienced conflict. They showed increased negative affect and decreased positive affect and toy exploration with conflicting signals compared with both happy and with fearful signals alone. Greater levels of lability were not found with conflicting signals. Marked differences among infants in capacity and style of coping with conflict were observed, as were a variety of specific conflict responses, such as agitated sucking, rocking, avoidance, extreme motor inhibition, aimless or disoriented behavior, and transient, unintegrated affect expressions. PMID- 2209189 TI - Hemispheric asymmetry in a face discrimination task in infants. AB - A right-hemisphere advantage in a mother's face recognition task in infants aged between 4 and 10 months was found to exist by de Schonen, Gil de Diaz, and Mathivet. The present study was designed to test (a) whether the right-hemisphere advantage would still prevail if the task requirements were different from those in the previous study, and (b) whether any information was communicated from one hemisphere to the other. 18-42-week-old infants were presented with an operant conditioning situation where they had to discriminate between their mother's and a stranger's face within one visual hemifield. Transfer of learning from one visual hemifield to the other was also measured. The results confirm the existence of a right-hemisphere advantage in discriminating between face stimuli. This advantage was weaker in the female than in the male population. No hemispheric transfer of learning was observed to occur. PMID- 2209190 TI - Activities and interactions of mothers and their firstborn infants in the first six months of life: covariation, stability, continuity, correspondence, and prediction. AB - Activities of primiparous mothers and infants were observed at 2 and 5 months of age during naturalistic interactions at home. 5 prominent features of mother and infant exchanges in this short-term longitudinal study are described and discussed in the context of 3 models of unique environment-development relations: covariation, stability, continuity, correspondence, and prediction. Generally, mothers' activities did not positively covary at either age, nor did those of infants. Some maternal activities were stable in this time period; some developmentally increased, and some developmentally decreased. Infants' activities were unstable, but most increased over time. Specific mother and infant activities corresponded, and over time mothers and infants influenced one another in specific ways. In the critical period of the first half year, infants appear to be flexible and plastic in their behavioral repertoires and are influenced by their mothers; mothers are somewhat consistent, but they also adapt to the behaviors of their infants. PMID- 2209191 TI - Adults' tolerance of cries: an experimental investigation of acoustic features. AB - Variations in the aversiveness of a newborn's distress cry were examined using experimental manipulation of 3 acoustic features of the cry (fundamental frequency, intonation, spectral complexity) and of the information given to subjects about the infant's health status. The subjects (N = 164 medical students) were allowed to control the sound pressure level (range: 50 dB [A]-105 dB[A]) of the different cry versions by repeatedly pressing a button (operant titration). For the nonmanipulated (original) cry version, the accepted sound pressure level decreased as fundamental frequency increased at above 610 Hz. This effect was modified by experimental manipulation of spectral complexity as well as intonation. A preference of intonated cries over monotonous cries was most pronounced between 534 and 686 Hz. Significant interactions of the information variable with the intonation and the complexity variables suggest that the listener's reaction to certain physical cry characteristics can be altered substantially by inducing different cognitive sets. PMID- 2209192 TI - Neonatal temperament in monozygotic and dizygotic twin pairs. AB - To determine if neonatal temperament was influenced by genetic factors, temperament was assessed in 316 newborn twins from 47 pairs of monozygotic (MZ) twins, 39 pairs of same-sex dizygotic (DZ) twins, and 72 pairs of opposite-sex dizygotic twins. The neonatal assessment focused on irritability, resistance to soothing, activity level, reactivity, and reinforcement value. Examination of intraclass correlations for MZ and DZ twins and the results of model-fitting analyses indicated that heritability estimates for neonatal temperament were not significantly different from zero, and that there was substantial environmental influence on neonatal temperament. Specific perinatal indicators of risk were found to account for some of the intrapair differences observed for the behavioral variables. It was concluded that there is no clear pattern of genetic influence on temperament in the neonatal period. PMID- 2209193 TI - The control of reaching movements by young infants. AB - Samples of reaches were obtained from groups of infants aged 4.5, 6, and 7.5 months. Split-screen video recordings were transcribed as sequences of (x,y,z) hand coordinates, and the hand path was examined for evidence of initial aiming and subsequent correction of the movement path. At all ages, the initial direction of the movement was correlated with target direction, providing evidence that the hand was aimed toward the target. Additionally, changes in movement direction made after the commencement of the movement tended to curve the hand path toward the target, providing evidence of error correction. Local minima of hand speed evident within segments of continuous motion were associated with turn toward the target. However, the movement path was also curved toward the target within the movement elements bounded by these minima. This finding was seen as consistent with "continuous" correction of movement errors and as contrary to the suggestion that infant movements are concatenations of ballistic movement units whose boundaries are marked by troughs in the speed profile. PMID- 2209194 TI - Infants' localization of sounds within hemifields: estimates of minimum audible angle. AB - Infants' acuity in localizing sounds within hemifields was examined by determining the smallest sound shift off 60 degrees and along the horizontal axis that infants could discriminate reliably, that is, minimum audible angle (MAA). Infants 6, 12, and 18 months of age were tested using a Go/No-Go conditioned head turn procedure in which infants received an equal number of no-change (control) trials and sound-shift (experimental) trials. A correct response (i.e., a head turn toward the loud-speakers) on an experimental trial resulted in visual reinforcement. Localization acuity for sounds within hemifields was fairly poor and improved systematically with increasing age. MAA estimates at each age were significantly higher, indicating poorer localization acuity, in comparison to those obtained previously in research examining infants' resolution of auditory space near midline. These findings are consistent with adult data and demonstrate a finer partitioning of auditory space near midline than within hemifields. The implications of these findings for our understanding of the development of auditory processing mechanisms in sound localization are discussed. PMID- 2209195 TI - Behavioral and electrophysiological evidence for gestational age effects in healthy preterm and fullterm infants studied two weeks after expected due date. AB - We investigated the effects of gestational age at birth on behavioral and electrophysiological measures of 135 medically healthy infants, studied at 42 weeks postconception, and stratified into 3 groups--early-born preterms, 26-32 weeks (n = 55); middle-group preterms, 33-37 weeks (n = 43); and fullterms, 38-41 weeks (n = 37). Subjects were studied behaviorally with the Assessment of Preterm Infants' Behavior (APIB) and electrophysiologically with brain electrical activity mapping (BEAM). Fullterms showed significantly better behavioral function than both preterm groups. Less difference was found between the preterm groups. EEG spectral and photic evoked response were of significantly less amplitude for the preterms than the fullterms. Path analysis showed gestational age effects on behavioral (3 of 6) and electrophysiological (13 of 17) variables due to postnatal complications. We conclude that some differences attributable to gestational age at birth are explained by the cumulative effect of minor but unavoidable complications associated with premature birth. We speculate that remaining effects may result from developmentally inappropriate sensorimotor stimulation consequent to the premature experience of an extrauterine environment. PMID- 2209196 TI - Young children's understanding of fact beliefs versus value beliefs. AB - Recent research on the development of children's knowledge about the mind has shown that young 3-year-olds have difficulty inferring that another person holds a false belief about a matter of verifiable fact, even when provided with considerable help. 4 studies tested the hypothesis that they would have less difficulty inferring that another person holds an odd, nonnormative belief about a matter of taste or value--one which, like the false fact belief, they themselves do not hold. On fact-belief tasks, an experimenter acted as if, or even explicitly stated that, she believed that the contents of a container were other than what the children knew to be the case. On value-belief tasks, she behaved as if she believed that a stimulus had a good or bad taste, smell, or appearance, whereas they thought it had the opposite. The results of all 4 studies confirmed the hypothesis. PMID- 2209197 TI - Inferring false beliefs from actions and reactions. AB - Current evidence suggests that young children have little understanding of false belief. Standard false belief tasks, however, may underestimate children's ability for 2 reasons. First, the only cue to belief in these tasks is a protagonist's lack of perceptual access to some critical event, and this may not be a very salient cue for young children. Second, the standard tasks require children to make forward-looking predictions from the causes of a belief (e.g., from what a protagonist has or has not perceived) to either the protagonist's belief or the protagonist's action, and children may not be very skilled at making such predictions. In 2 experiments we investigated whether 3-year-olds would do better on tasks in which the belief cues were stronger, and in which they could reason backward to the belief from its effects (e.g., from a protagonist's actions and reactions). Even on these easy tasks, however, they did not perform well. These findings provide strong support for the view that children of this age do not fully understand the representational nature of belief. PMID- 2209198 TI - Young children's understanding of realities, nonrealities, and appearances. AB - In 2 studies we uncover some of children's earliest conceptions of various realities, nonrealities, and appearances. In the first study, we investigated children's early understanding by examining their use of the words real and really in spontaneous speech. These natural language data consisted of longitudinal samples of 6 children's speech between the ages of 1 and 6 from the Childes database. Analyses of these samples showed that by age 3 children clearly distinguished between reality and a variety of nonreal contrasts in their everyday speech. For example, young children distinguished between toys, pictures, and pretend actions versus their real natures. We claim that, in making these distinctions, children often are considering appearances, broadly construed. To confirm this, we conducted a second experimental study with 3-year olds, in which we questioned children about the reality and appearance of a variety of items. Results from this study confirm and clarify our findings from the natural language data. We discuss the implications of these studies for current descriptions of young children's understanding of realities and nonrealities, including their understanding of the distinction between reality and appearance. PMID- 2209200 TI - Young children understanding that looking leads to knowing (so long as they are looking into a single barrel). AB - 3 experiments were conducted to investigate the claim made by Wimmer, Hogrefe, and Perner that 3-4-year-old children do not understand that people gain knowledge about something by looking at it. The first experiment involved a simple forced-choice procedure in which children had to judge which of 2 assistants knew what was inside a box when one of the assistants had looked inside and the other had lifted it up. In this experiment, the children did realize that the assistant who had looked in the box knew its contents. The second experiment followed the Wimmer et al. procedure, but with a simpler question form. The children were just asked to state whether someone knew what was in the box. Again, the children were able to work out that a person who had looked in a box knew what was inside it. In the third experiment, a direct comparison was made between the simpler question and the more complex, double barreled question asked by Wimmer et al. The children found the more complex question considerably harder. The results of these experiments suggest that, in contrast to the claims made by Wimmer et al., 3- and 4-year-old children do understand that looking leads to knowing, and that their difficulty in the Wimmer et al. study was mainly with the form of the question that they were asked. PMID- 2209199 TI - If you had my brain, where would I be? Children's understanding of the brain and identity. AB - When do children distinguish a person's subjective identity from their outward bodily characteristics? As adults this distinction is evident in our commonsense recognition that a hypothetical brain transplant would entail a transplant of the mind or self. 4 studies were conducted to examine children's judgments about hypothetical body part transplants, including transplants of the brain, heart, mouth, and face. The results showed that during the elementary school years children are acquiring a firm understanding of the brain as the primary locus of psychological attributes and identity. The early school years, between the ages of 5 and 7 years, appeared to be a transitional phase, with performance being variable and subject to task conditions. While children this age readily imagined the consequences of transplants between themselves and another character of categorically different status (i.e., a pig or baby), they had great difficulty with proposed transplants between themselves and another child of the same status. Knowledge about categorical differences appeared to provide a needed framework for children's budding thinking about psychological differences. PMID- 2209201 TI - Visual and verbal metaphors: developmental interactions. AB - This study investigated developmental changes in children's abilities to comprehend visual metaphors as measured by their use of verbal metaphor. The visual metaphors were compound objects, e.g., a top with features of a ballerina (head and skirt). 30 participants at each of 4 ages--5, 7, 10, and adult- described objects ordered in pairs; half described standard objects and the other half corresponding compound objects (half stationary, and half moving, e.g., spinning). Total metaphoric descriptions reached the adult frequency by age 7 for compound objects, but increased from 5 to 10 to adult for standard objects. For all but the youngest children, moving objects were more likely to be described using action vehicles. These results indicate that from 5 to 7 children improve in the ability to understand visual metaphors, which display topic-vehicle interaction; from 5 through 10 to adulthood they improve in the ability to comprehend metaphoric similarity. PMID- 2209202 TI - Age differences in imagery abilities. AB - Age differences were examined in 4 aspects of visual mental imagery, namely, image generation, maintenance, scanning, and rotation. The results suggested that one or more distinct processes are used to carry out each aspect of imagery, and that this is true for 5-year-olds, 8-year-olds, 14-year-olds, and adults. There was no evidence that younger children have fewer processing components, which become differentiated into more specialized subsystems over age. In addition, the results suggested that younger children are relatively poor at scanning, rotating, and generating objects in images, but are relatively good at maintaining images. PMID- 2209203 TI - Intrathecal injection of Iohexol for routine myelography and CT myelography in 1,000 cases. AB - This article is to present the experience in 1,000 cases given intrathecal Iohexol injection during 1985-1988, including conventional myelography in 343 cases, conventional and CT myelography in 572, only CT myelography in 60 and CT cisternography in 25. No convulsions were observed. The frequency of headache was 11.6% and the total uncomfortable subjective reaction was 19.6% after intrathecal injection, but no serious complications were found. Because of very low frequency of side effects after this injection, most of the examinations can be made in the outpatient departments. In our clinical experience, Iohexol appears to be a myelographic contrast medium with diagnostic capabilities and less morbidity compared to Metrizamide. Thus Iohexol seems to be well suited for intrathecal injection and will replace metrizamide in this respect. PMID- 2209204 TI - [Orientation of molar implants]. PMID- 2209206 TI - [Kinesiology and occlusal disturbance. Statistical study]. PMID- 2209205 TI - [Relationship between the incisal papilla and anterior teeth in dentate patients. Its use in placement of artificial teeth]. PMID- 2209207 TI - [Dental office of January 1, 1993. Its telecommunications]. PMID- 2209208 TI - [Rationalization of rotary instrumentation. Choice of instruments, choice of methods, choice of positions]. PMID- 2209209 TI - [Ergonomic principles of work station organization]. PMID- 2209211 TI - [Work space and essential criteria for choice]. PMID- 2209210 TI - [Automated equipment at the chair]. PMID- 2209212 TI - [Dental office organization in 1990: the role of automation]. PMID- 2209213 TI - [Role of the architect in ergonomic organization of the dental office]. PMID- 2209214 TI - [The "secondary" epidemic]. PMID- 2209215 TI - [Preovulatory human oocyte and its hormonal microenvironment in stimulated cycles]. AB - The hormonal microenvironment of 213 follicles in 44 stimulated cycles was analysed. Mature and intermediate oocytes were found to be associated with larger follicles which contained significantly higher levels of E2, P, FSH and LH, while smaller follicles containing significantly higher T level usually gave rise to immature oocytes. The fertilization rate was higher in mature and intermediate oocytes than in immature oocytes. In this study there was no significant difference in the cleavage rate of the fertilized eggs in relation to the E2, P, T, FSH and LH concentrations in follicular fluid as well as to the contents of these hormones per follicle. PMID- 2209216 TI - [Action of low-dose estrogen and progestogen on the relief of climacteric symptoms and excretion of urinary calcium]. AB - The effects of low-dose estrogen and progestogen on menopausal symptoms and urinary excretion of calcium were studied with Kuppermen score and fasting morning urine Calcium/Creatinine (Ca/Cr) ratio, respectively, in 69 perimenopausal women. The women were divided into 3 groups: amenorrhea less than 1 year (14 women); post menopause 1 approximately 3 years (19); and post menopause more than 3 years (36). Fasting urine Ca/Cr ratio in the postmenopausal group 1 approximately 3 years was 0.19 +/- 0.01, significantly higher than that (0.14 +/- 0.01) in the amenorrhea group less than 1 year and (0.11 +/- 0.006) the postmenopausal group more than 3 years. 18 women received sequentially 4 patterns of low-dose oral estrogen and progestogen: MPA 2 mg Q O D., EE 5 micrograms Q D, EE 5 micrograms Q O D, and EE 5 micrograms and MPA 2 mg Q O D alternately. Each pattern was used for 3 weeks and discontinued for an interval of two 2 weeks, then started the next pattern and so on EE 5 micrograms and MPA 2 mg Q O D alternately gave the best results both in improving symptoms and lowering urine Ca/Cr ratio. Seven women having intermittent large dose EE 50 micrograms every 10 days or Premarin 2.5 mg every 7 days had symptoms relieved but inconsistent decrease of urine Ca/Cr ratio. PMID- 2209217 TI - [Preliminary study on 4 indices of basal body temperature in the evaluation of luteal phase insufficiency after clomiphene treatment]. AB - The luteal phase insufficiency after Clomiphene treatment in 90 patients with polycystic ovary syndrome (PCOS) and other menstrual disorders was evaluated by four indices of BBT. The four indices of BBT are (1) BBT curve classification; (2) High phase score (HPS); (3) Planimetric nidation index (PNI); (4) Length of follicular phase. 90 patients (248 cycles) were divided into two groups: non pregnant group (214 cycles) and pregnant group (34 cycles). The result indicated that 70% cycles of non-pregnant group, the types of BBT are type III-VI, HPS is less than 9; the mean value of PNI is 45.7; the follicular phase lists beyond 17 days, with a mean of 18.6 days. More than two-thirds of the study cycles are abnormal at least in two indices. In all cycles of the pregnant group, BBT curve are of type I, II, HPS greater than 9, PNI greater than 57. The results suggest that measurement of the four indices of BBT is a simple method which could be widely used for the evaluation of luteal phase insufficiency. PMID- 2209218 TI - [Significance of detecting meconium-like substance in maternal urine in perinatal monitoring]. AB - Urinary meconium index (UMI) was determined in 538 cases of pregnant women by spectrophotometry (265 cases were in late pregnancies 229 in the first stage of delivery, and 44 in the second stage). The results indicated that most of those having positive UMI were high-risk pregnancies (P less than 0.01). The UMI index of the meconium contaminated amniotic fluid was higher than the non-contaminated amniotic fluid (P less than 0.01), and patients with lower Apgar score had higher rate of positive UMI. In consecutive measuring, , We found that the rate of neonatal asphyxia was highest in those with a UMI of falling type, and then in the rising type. It showed that measurement of maternal UMI is of value in monitoring high-risk pregnancies. PMID- 2209219 TI - [Study of Doppler flow velocity wave forms of the fetal umbilical artery]. AB - 400 umbilical arterial wave forms were determined in 120 cases of normal pregnancy. The systolic/diastolic (S/D) ratio of umbilical doppler flow velocity wave declined gradually from 3.3 to 2.2 during the period of 28th to 40th week, It was shown that the utero resistance was reduced and the placental blood perfusion was good. 67 umbilical arterial wave forms were determined in 33 cases of pregnancy induced hypertension. There were 20 cases of IUGR or fetal distress with abnormal umbilical arterial S/D ratio. The incidence of IUGR was 27% (9/33). The results show that this is a good, non-invasive and practical method for predicting fetal outcome. In combination with NST and biophysical profile it can serve as an antepartum assessment of fetal well being and is of much valve to eugenics and perinatology. PMID- 2209220 TI - [Prevention and treatment of complications in twin gestation]. AB - From Sept. 1987 to Oct. 1988, a collaborative program of preventing and treating the common complications of nulliparous twin gestations, namely pregnancy induced hypertension, anemia, premature labour and postpartum hemorrhage was carried out in nine hospitals according to the same plan. There were 91 subjects who met the above criteria (treated group) and 99 cases not included in the plan (control group). The incidence of pregnancy induced hypertension was 33%, anemia 13.2%, postpartum hemorrhage 6.6%, and perinatal mortality 22%, in the treated group. The mean duration of pregnancy was 38.38 weeks (268.7 days) and the mean neonatal birth weight was 2725.8 g. The rate of maternal and fetal complications and prenatal mortality in the treated group were significantly lower than those of the control group. PMID- 2209221 TI - [Outcome of pregnancy complicated by hepatitis A in the urban districts of Shanghai]. AB - In 1988, during an epidemic 431 cases of hepatitis A among a group 7,476 pregnant women were in the 12 Women Health Units at urban area of Shanghai, accounting for a morbidity rate of 5,765.1/100,000 pregnant women. The ratio of spontaneous abortion, induced abortion and term delivery were 18:15:67. There were 16 perinatal deaths in the 288 delivered cases. The perinatal mortality rate was 55.6/1,000 and its relative risk, as compared with that of the whole Shanghai Urban Districts was 4.1, at the same time, 83 cases of pregnancies associated with Hepatitis A (all confirmed by anti-hepatitis A Virus IgM assay) were studied in detail in the Shanghai Municipal Women Health Institute. The average birth weight of the new born was slightly lower and the mortality rate was significantly higher than those in a control group of 168 cases, there was no fetal infection as evidenced by fetal blood anti HAV IgM. PMID- 2209222 TI - [Ovarian sex cord stromal tumors with annular tubules: a report of 6 cases]. AB - Six patients with ovarian sex cord stromal tumor with annular tubules (SCTAT) were diagnosed and treated from 1968 through 1988, accounting for 6% of a total of 99 cases of ovarian sex cord stromal tumors admitted during the same period. Of these, 3 were operated on for the first time and 3 were recurrent cases referred from other hospitals. The menstrual disturbance was characterized by menometrorrhagia followed by sustained amenorrhea. Glandular atrophy and decidual change of stromal were observed in 3 of the 4 endometrial samples available for histologic examination. Serum hormone assays carried out in 2 cases revealed elevated levels of both estradiol and progesterone. The primary tumor was unilateral in 5 cases and bilateral in one the recurrent tumors were exclusively retroperitoneal and ipsilateral to the primary ovarian tumors. In these cases, lymphatic metastasis was also observed in the ipsilateral pelvic lymph nodes. Complete and sustained remission has been achieved in all 3 patients receiving primary surgery by unilateral salpingo-oophorectomy. After removal of the metastatic tumors in 3 recurrent cases, 2 have survived with residual diseases for 2 and 9 years respectively and one died 4 years after the secondary surgery. PMID- 2209223 TI - [Parovarian cysts]. AB - Histologic material from 117 cases of parovarian cysts through 1979 to 1984 was reviewed. The majority of these lesions were paramesonephric (mullerian), mesonephric and mesothelial in origin. Most patients were without symptoms. On microscopic examination a basement membrane may be demonstrated beneath the mesonephric epithelium, although such a layer is usually absent in the mullerian structures. Eight specimens show stratification of the epithelial lining of the papillae, four of these are parovarian cysts of low grade malignancy. These neoplasms were associated with normal tubes and ovaries. Follow up data on four low grade malignant cases showed they were living and well. PMID- 2209224 TI - [Gonadoblastoma: a report of 3 cases]. AB - Three cases of gonadoblastoma are presented. All the patients are phenotypic female and sexually abnormal. The chromosomal karyotypes are 46; XY in two, the another one is 46, XX/46, XY/47, XXY mosaicism. Streak gonads and hypertrophy are noticed. The pathologic characteristics are discussed in detail in relation to the clinical picture. PMID- 2209225 TI - Molecular differentiation of the homomorphic sex chromosomes in Megaselia scalaris (Diptera) detected by random DNA probes. AB - Randomly cloned DNA fragments and a poly-(GATA) containing sequence were used as probes to identify sex chromosomal inheritance and to detect differences at the molecular level between the homomorphic X and Y in the phorid fly, Megaselia scalaris. Restriction fragment length differences between males and females and between two laboratory stocks of different geographic origin were used to differentiate between sex chromosomal and autosomal origin of the respective fragments. Five random probes detected X and Y chromosomal DNA loci and two others recognized autosomal DNA loci. One random probe and the poly(GATA) probe hybridized with both sex chromosomal and autosomal restriction fragments. Most of the Y chromosomal restriction fragments were conserved in length between the two stocks while most of the X chromosomal and autosomal fragments showed length polymorphism. It was concluded, therefore, that the Y chromosome contains a conserved segment in which crossover is suppressed and restriction site differences have accumulated relative to the X. These chromosomes, therefore, conform to a theoretically expected early stage of sex chromosome evolution. PMID- 2209226 TI - Analysis of DNA replication during S-phase by means of dynamic chromosome banding at high resolution. AB - The characteristic patterns of dynamic banding (replication banding) were analysed. Extremely high resolution (850 to 1,250 bands per genome) G- and R-band patterns were obtained after 5-bromo-2'-deoxyuridine (BrdUrd) incorporation either during the early or the late S-phase. We synchronized human lymphocytes with high concentrations of thymidine or BrdUrd as blocking agents, followed by low concentrations of BrdUrd or thymidine respectively as releasing agents, and obtained R- or G-band patterns respectively. The dynamic R- and G-band patterns were complementary for all chromosomes, even for the late-replicating X chromosome. There was no overlapping and every part of each chromosome was positively stained by one of the two banding procedures. The complementarity of the two patterns shows that both high thymidine and high BrdUrd concentrations blocked S-phase progression near the R-band to G-band replication transition in the middle of S-phase. Some bands of the inactive X chromosome replicate before this transition concurrently with R-band replication. The 48 different telomeric regions could be classified into 5 distinct morphotypes based upon the distribution of early and late-replicating DNA in each telomeric region. The dynamic band patterns are particularly useful for the study of the structural and physiological organization of chromosomes at high resolution and should prove invaluable for assessing the replication behavior of rearranged chromosomes. PMID- 2209227 TI - Heterogeneity and maintenance of centromere plasmid copy number in Saccharomyces cerevisiae. AB - We developed a novel approach to quantitate the heterogeneity of centromere number in yeast, and the cellular capacity for excess centromeres. Small circular plasmids were constructed to contain the CUP1 metallothionein gene. ARS1 (autonomously replicating sequence) and a conditionally functional centromere (GAL1-GAL10 promoter controlled centromere). The CUP1 gene provided a gene dosage marker, and therefore a genetic determinant of plasmid copy number. Growth of cells on glucose is permissive for centromere function, while growth on galactose renders the centromere nonfunctional and the plasmids are segregated in an asymmetric fashion. We identified "lines" of cells containing increased numbers of plasmids after transformation. Cell lines containing as many as five to ten active centromeres are stably maintained in the absence of genetic selection. Thus haploid yeast cells can tolerate a 50% increase in their centromere number without affecting progression through the cell cycle. This system provides the opportunity to address issues of specific cellular controls on centromere copy number. PMID- 2209228 TI - [The significance of HBsAg and HBcAg levels in the liver and their relation to histopathologic activity]. AB - The results of histological and immunohistological studies on the liver biopsies from patients with positive serum HBsAg, HBeAg, HBVDNA, and HBVDNAp showed: 1. In addition to the inclusion body like, marginal, diffuse and membranous patterns of HBsAg, we found that marginal and diffuse patterns of HBsAg may appear within one hepatocyte and this is named as transitional pattern. A preliminary suggestion about the process of formation and evolution of different patterns of HBsAg and HBcAg was raised. 2. There is a relationship between HBV replication and the activity of hepatitis. Different patterns and distributions of HBAg affect the lesion of the liver significantly. 3. According to the morphology of HBsAg and HBcAg, we suggest to divide their patterns into the following two categories: The first includes the diffuse and membranous patterns of HBsAg and the cytoplasmic and membranous HBcAg; these are related to the replication of HBVDNA. The second includes inclusion body like and marginal patterns of HBsAg with and without nuclear pattern of HBcAg; these probably reflect the integration of HBVDNA to the host genome. PMID- 2209229 TI - [A study of the relation of the expression of beta-microglobulin and hepatocytic lesions in hepatitis B]. AB - Beta 2-Microglobulin expression on hepatocyte membrane was studied in 117 liver biopsies from patients with acute and chronic hepatitis B and in 11 subjects with normal liver function, using immunohistochemical PAP method. In normal liver beta 2-microglobulin could not be detected on hepatocyte membrane, compared with that in subjects with normal liver, in asymptomatic HBsAg carrier and in patients with chronic persistent hepatitis, there is significant enhancement of beta 2 microglobulin expression in patients with acute mild hepatitis and chronic mild active hepatitis. Beta 2-Microglobulin expression in patients with chronic active hepatitis with moderate to severe activity and cirrhosis has a significant enhancement, when compared with acute mild hepatitis and chronic mild active hepatitis. Moreover, location of beta 2-microglobulin expression on hepatocyte membrane was associated with lesion of hepatocytes. Enhanced expression of beta 2 microglobulin on hepatocyte membrane in acute and chronic hepatitis B probably reflects enhanced display of HLA-ABC antigens and may influence the course of hepatitis B virus infection by increasing susceptibility of T cell-mediated hepatocytelysis. PMID- 2209231 TI - [Adverse and toxic reaction to amiodarone and its interaction with other drugs]. PMID- 2209230 TI - [Effect of rifampin on the metabolism of glucocorticoids in Addison's disease]. AB - To investigate the effect of rifampicin on the metabolism of hydrocortisone, we measured serum sodium level and blood glucose concentration before lunch in a patient with Addison's disease when treated with hydrocortisone 30 mg/day alone and together with rifampicin 450 mg/day for more than two weeks. We also studied the area under the plasma cortisol curve (AUC), half-life (T 1/2) and clearance rate (CLs) of hydrocortisone after both oral ingestion and intravenous injection of 20 mg hydrocortisone. The results showed that rifampicin increased the metabolism of cortisol by shortening of its T 1/2, increasing its CLs and decreasing its AUC. It decreases the blood sodium level and glucose concentration and makes the patient liable to have hypoglycemic symptoms before lunch. We conclude that the increase of metabolism of cortisol after simultaneous taking of rifampicin may induce adrenal crisis in Addison's disease. PMID- 2209232 TI - [Prognosis of severe organic phosphorus pesticide intoxication and the effect of atropine treatment: analysis of 506 cases]. AB - The results of atropine treatment in 506 cases of severe organic phosphorus pesticide intoxication are reported. Among the variables which might effect the results of treatment, the average dosage of atropine was related intimately to the prognosis (standard coefficient of regression bi = 0.4702, P less than 0.01). When the average drug dosage was 40-80 ng/h, the mortality was 26.6% and much lower than other groups (P less than 0.01). Intravenous administration given at regular intervals was better than continuous drip; the mortality dropped to 61.2% from 90.9% (P less than 0.01). Both inadequate atropinization and atropine intoxication were less frequently seen during intermitten injection (P less than 0.01). PMID- 2209233 TI - [Chronic alcoholism with diffuse brain atrophy]. AB - An analysis of clinical manifestations and CT scan of 9 cases of chronic alcoholism was reported. It is shown that there are diffuse brain atrophy in chronic alcoholism patients with neuro-psychiatric symptoms. There were significant relations among clinical history, amount of alcohol consumed and brain atrophy. It should also be mentioned that the number of young alcoholics is more than that of elderly. This problem must be paid attention to. PMID- 2209234 TI - [Coronary thrombolysis with defibrase]. AB - Clinical use of defibrase (DF), a fibrinolytic agent from venom of Agkistrodon acutus, was investigated in patients with acute myocardial infarction (AMI). Patients with AMI were randomized to tow groups, one receiving conventional therapy and DF, the other a control group having conventional treatment only. The patients in the DF group received intravenous DF 0.05 u or 0.075 u/kg over 1 hour immediately after the attack and 0.025 u/kg over 4 hours on the 5 th and 10 th day. The control patients received conventional therapy only. Of the patients randomized, 21 had coronary angiography and left ventriculography. Recanalization was seen in 10 of the 10 patients treated with DF, while only in 3 of the 11 patients in the control group. LVEF in the DF group was higher than that in the control group (61% vs 50%). However the difference was not significant. In the DF group, two patients developed petechia and blood oozing at the site of intravenous injection and one patient developed gum bleeding; all patients had transient thrombocytopnia, which returned to normal within 5 days. There was no intracranial hemorrhage, gross hematuria or hematemesis. In conclusion, DF possess thrombolytic as well as anticoagulant effects with minor bleeding complication. Early infusion of DF yields high patency rate and shows a trend toward preservation of LV function. PMID- 2209235 TI - [Relation of left ventricular compliance and heart size]. AB - 53 patients with myocardiopathy were studied to determine the left ventricular compliance (LVC) with apexcardiography and the heart size with radiography. Relation between LVC and heart size was analysed by using linear correlation. In cardiomyopathy LVC decreased and correlated with the size of heart. It was concluded that the size of heart was one of factors which influenced LVC. The decrease of LVC may be related with the length of myocyte, the geometric shape of heart and histopathologic alteration. PMID- 2209236 TI - [Pulmonary Pseudomonas infections]. AB - 145 strains of pathogenic pseudomonas had been isolated from the sputum or bronchoscopic aspirate of 1423 patients with pulmonary infections. They were classified into 8 types, among which 31.7% was pseudomonas aeruginosa. Pseudomonas aeruginosa was the dominant causative organism in pulmonary infections of the aged while in presenile ones the organism was mainly Pseudomonas fetid. The incidence of nosnocomial pseudomonas infection in patients of COPD with respiratory failure was 40%, of COPD with pulmonary infection 9.1% and of others 6.6%. 24 pseudomonas carriers with COPD (colonies less than or equal to 10(6)/ml in sputum) had been followed up. 16 out of them became negative in sputum culture without any treatment, while the remaining 8 developed pulmonary pseudomonas infections. 21 patients (14.5%) were found to have other types of pseudomonas infections during antibiotic treatment. Sensitivity tests showed that third-generation cephalosporins and aminoglycosides had definite antimicrobial activity against pseudomonas, the former being more stable and effective than the latter. PMID- 2209237 TI - [Diagnosis of cyanosis and digital clubbing caused by liver cirrhosis]. AB - Six cases of cyanosis and digital clubbing caused by liver cirrhosis were reported. The mean levels of PaO2 and PaCO2 were 6.4 +/- 0.8 kPa (48.3 +/- 6.2 mmHg) and 3.9 +/- 0.8 kPa (29.5 +/- 6.1 mmHg) respectively. The cause of cyanosis and digital clubbing in liver cirrhosis was discussed. Abnormal intrapulmonary shunting (IPS), which was proved in 4 cases by whole-body radionuclide scanning with 99mTc-MAA, is suggested as the major cause of cyanosis in liver cirrhosis. Clinically IPS is usually associated with debilitating conditions characterized by hyperventilation, abnormality of lung diffusion and orthodeoxia or platypnea. The authors suggest that whole-body radionuclide scanning with 99mTc-MAA may be performed for establishing IPS if liver cirrhosis is highly suspected to be the cause of severe hypoxemia. PMID- 2209238 TI - [Prognostic factors in the acute stage of myocardial infarction: analysis of 893 cases]. AB - The prognostic factors in the acute stage of 893 myocardial infarction patients, admitted during a period from 1970 to 1986, were analysed. The overall mortality was 15.6%, including 14.4% cardiac death and 1.1% non-cardiac death. Single factor analysis indicated that age, sex, occupation, history of hypertension, chest pain during the episode, systolic blood pressure, heart rate and site of infarction at the time of admission, presence of complications such as cardiogenic shock, arrhythmias, stroke and monitoring in CCU or not were related to the overall mortality and cardiac death. Multiple factor logistic regression analysis indicated that for the overall mortality, the independent prognostic factors included presence of cardiogenic shock, heart rate and chest pain at the time of admission; for the cardiac death, the independent factors included age, occupation, history of hypertension, heart rate and chest pain at the time of admission, involvement of anterior wall and presence of cardiogenic shock and arrhythmias. Basing on the above findings we establish a risk factors predicting prognostic model of acute myocardial infarction in its acute stage. PMID- 2209239 TI - [Diagnosis of myocarditis with endomyocardial biopsy]. AB - Endomyocardial biopsy (EMB) was performed in 24 cases suspected of having myocarditis and 42 cases with cardiac symptoms and signs of unknown etiology. There was an obvious correlation between the clinical manifestations and the pathological findings in cases suspected of having myocarditis (r = 0.5296, P less than 0.005). The ratio of correspondence was 78.8%. It is shown that EMB is more sensitive than 201TI myocardial imaging in diagnosing myocarditis and serial EMB can follow its clinical process closely. Moreover, EMB can discriminate myocarditis from myocardiopathy. PMID- 2209240 TI - [Chronic active hepatitis with superinfection of delta virus and hepatitis B virus: treatment with Chinese traditional medicine]. AB - Among the 136 patients of HBsAg positive chronic hepatitis admitted from November 1986 to June 1988, 110 patients gave consent to have liver biopsy and out of the 110 liver biopsies 86 were confirmed histologically to be chronic active hepatitis. After screening the 86 patients twice with ELISA (ABBOTT ANTI-DELTA EIA), 26 (30.23%) showed positive results twice. Though it was reported that the incidence of delta hepatitis infection is very low in the HBsAg carriers in Beijing area, the incidence of superinfection of delta hepatitis on chronic active hepatitis B seems to be considerably high (30.23%) as shown in this study. Histological examination revealed that in the liver of patients with superinfection of delta hepatitis on chronic active hepatitis (26 cases) there were more severe changes and more eosinophilic degeneration than in the liver of patients without superinfection (58 cases). The patients were allocated to 3 groups at random. Eleven cases of chronic active hepatitis, with superinfection were treated with Chinese traditional medicine Xiao Chai Hu Tang (XCHT), 5 cases with biphenyl dimethyl dicarboxylate (BDD) and 10 cases with XCHT + BDD. It was noted that after 3 months of treatment, in the XCHT group, HBeAg became negative in 2/3, anti-HBe converted to positive in 2/8 and HBV-DNA converted to negative in 2/2. SGPT became normal in 8/8. XCHT showed a fairly good result and deserves further study. PMID- 2209241 TI - [Effect of sclerotherapy in patients with bleeding due to portal hypertension]. AB - The author reports the preliminary results of an unrandomized trial comparing the effect of endoscopic variceal sclerosis, shunt surgery and medical therapy in the management of cirrhotic patients with variceal bleeding, sixty-six patients were studied, among them 23 received sclerosis, 25 shunt surgery and 18 medical therapy. Survival was significantly (P less than 0.001) improved in the group with sclerotherapy, with 85% one year survival rate as compared with 45% in the group with shunt surgery and 21% in the group with medical therapy. PMID- 2209242 TI - [A new monoclonal antibody against human tubular brush border: preparation and its application in membranous nephropathy]. AB - A new monoclonal antibody (McAb) against human tubular brush border was successfully prepared by authors using the hybridoma technique. The McAb produced was identified to be isotype of IgG1 by IF and SDS-PAGE assay. It was unique for its purity and specificity. To demonstrate the clinical usefulness, the McAb was applied for immunopathological study in 94 cases of renal biopsy of glomerular diseases. This McAb was distinguished by its specific deposition along the human tubular brush border and the subepithelial region in certain type of glomerular disease, particularly the MGN. Identification of this McAb might contribute to the immunopathological diagnosis of GN. PMID- 2209243 TI - [Clinical observations and studies of BCG in the treatment of primary glomerulonephritis]. AB - Sixty cases of nephrotic type of primary glomerulonephritis (PGN), who were mostly insensitive to the corticosteroids, received killed BCG inoculation as a main measure of combined therapy. After this treatment the complete and approximate remissions accounted for 80% in all. The urinary protein, serum albumin, BUN and SCr all had very significant improvement. As to those with similar pathologic and clinical findings, the therapeutic effects were much better in the BCG group than in the control. 13/15 cases followed up over 1-2 years had complete remission at the latest follow up and 5/6 followed below 1 year did so. The longer the courses of BCG, the lower the recurrence rates. The therapeutic effects of retreatment to those recurrent cases were much more rapid than those of initial treatment. The phagocytic function of the monocyte in another 24 PGN cases was studied. This function was found to be significantly depressed and could be normalized through BCG inoculation. PMID- 2209244 TI - [Hemochromatosis: a review of 22 Chinese cases]. AB - 22 cases of hemochromatosis were analysed. 19 cases were collected from Chinese medical journals and 3 from our hospital. We showed the similarities and differences between Chinese and western patients. The diagnosis, mode of heredity, possible pathogenesis and management of idiopathic hemochromatosis were also briefly discussed. PMID- 2209245 TI - [Ultrastructural study of the megakaryocytes in megaloblastic anemia]. AB - The ultrastructure of the megakaryocytes in the bone marrow from 14 cases of megaloblastic anemia was studied. The commonest change observed was that the development of the nucleus lagged behind that of the cytoplasm. There were some evidences supporting the theory of ineffective thrombocytopoiesis. The mechanism of the relationship between the changes of morphology and function based on the impaired DNA synthesis and methylation due to folate and vitamin B12 deficiency were also discussed. PMID- 2209246 TI - [Antineuronal antibodies and neuropsychiatric systemic lupus erythematosus]. AB - Determination of antineuronal antibodies was carried out by a solid phase radioimmunoassay, in which the neuronal cells SK-N-SH were cultured as the target antigens, the positive rate in sera and CSF of neuropsychiatric SLE patients being 85% and 77.8% respectively, all with quite high level of antibodies. Although 66.7% sera of SLE patients without CNS involvement were also positive for the antibodies, yet the antibody levels of them were distinctly lower, and only 3 of them showed weak positive reactions in their CSF. It was shown that 90% of neuropsychiatric SLE patients with diffuse CNS manifestations had increased antineuronal antibodies, compared with only 20% in cases with local CNS involvements. The antibody levels both in sera and CSF decreased remarkably following the patients' recovery from the neuropsychiatric attack. It is concluded that the antineuronal antibodies might play a role in the pathogenesis of neuropsychiatric lupus and the determination of them in CSF might be useful in the diagnosis and differential diagnosis of neuropsychiatric lupus. PMID- 2209247 TI - [The application of plasma exchange therapy in refractory diseases]. AB - 115 plasma exchange (PE) procedures were performed in 27 patients using the Haemonetics V50 plasmapheresis system 20 patients improved; among them 15 improved remarkably. Adverse reactions were observed 30 times (26.1%). PE showed beneficial effects in certain disease states which did not respond to conventional treatment or traditionally known therapeutic measures, especially patients in critical condition. Prevention and treatment of associated infections are very important in order to obtain a better efficacy of PE. PMID- 2209248 TI - [Advances in the treatment of refractory multiple myeloma]. PMID- 2209249 TI - Symposium on the biology of nicotine dependence. London, 7-9 November 1989. Proceedings. PMID- 2209250 TI - Regulation of endocrine function by the nicotinic cholinergic receptor. AB - One important neuroendocrine action of nicotine in the male rat is an increase in the secretion of corticosterone which is seen upon acute and acute intermittent exposure to nicotine. Tolerance develops to this action of nicotine upon chronic exposure, and in the withdrawal phase serum corticosterone levels are substantially reduced. In contrast, no significant increases of serum corticosterone levels were observed upon acute intermittent treatment with nicotine in the dioestrous rat. Available evidence indicates that corticosterone can modulate dopamine transmission in the basal ganglia via glucocorticoid receptors within the nucleus accumbens and neostriatum, and via glucocorticoid receptor immunoreactivity in nigrostriatal and mesolimbic dopamine pathways. Through concerted pre- and postsynaptic actions glucocorticoids may decrease dopamine transmission, especially that mediated by D2 receptors in these regions. In view of the hypothesis that the mesolimbic dopamine pathways mediate the euphoric effects of nicotine, the secretion of corticosterone induced by nicotine in the smoking male may substantially influence the mood elevating activity of nicotine. Thus, individual smoking habits may depend on the ability of nicotine to induce corticosterone secretion, which obviously would also vary with the degree of stress. The glucocorticoids may in a similar way influence the arousal action of nicotine because of the high number of glucocorticoid receptors present both in noradrenaline cell bodies of the locus ceruleus and within the entire cerebral cortex. PMID- 2209251 TI - Effects of nicotine on cerebral metabolism. AB - Interest in identifying brain areas mediating the behavioural effects of nicotine led to autoradiographic studies on the distribution of cerebral metabolic responses to nicotine. The 2-deoxy-D-[1-14C] glucose method was used to map and quantitate nicotine's effects in the rat brain. The method allows simultaneous measurement of the regional cerebral metabolic rate(s) for glucose (rCMRglc), an index of functional activity, throughout the central nervous system. It provides information about sites of initial drug interactions, and of secondary effects propagated via afferents to remote areas. In rats given acute systemic ( )nicotine, stimulation occurs in brain areas which contain specific binding sites for [3H] nicotine, indicating that the sites are true receptors, linked to functional activity. Doses of nicotine that are discriminated by rats and that produce behavioural and physiological effects stimulate rCMRglc. The stimulation is transient and is antagonized by mecamylamine. Affected areas include limbic structures, components of the visual system, brainstem nuclei important in cardiovascular reflexes, and areas involved in motor function. The distribution of nicotine's in vivo effects on rCMRglc implicates various brain regions in the behavioural and physiological effects of nicotine. Future studies employing positron emission tomography will assess relations between nicotine's effects on mood and rCMRglc in man. PMID- 2209252 TI - Mesolimbic dopamine activation--the key to nicotine reinforcement? AB - The mesolimbic dopaminergic system appears to mediate the rewarding effects of certain stimulant drugs, such as (+)amphetamine. Autoradiographic mapping techniques have revealed that these neurons are potential targets for nicotine, since they possess nicotinic receptors located on their cell bodies and terminals in rat brain. Functional studies are consistent with this proposal: nicotine can increase the firing rate of these neurons, and nicotine-induced dopamine release has been demonstrated in vitro and in vivo. The locomotor stimulant effect resulting from the acute administration of nicotine is accompanied by, and appears to be dependent upon, activation of mesolimbic neurons. Likewise, destruction of this system appears to attenuate the acute rewarding effects of intravenous nicotine in rats. Thus, when administered intermittently, nicotine, like certain other stimulant drugs, may activate the mesolimbic dopamine system, and this action may contribute to the tobacco habit. PMID- 2209253 TI - Effect of nicotine on dynamic function of brain catecholamine neurons. AB - Burst firing in the mesolimbocortical dopamine (DA) neurons, originating in the ventral tegmental area (VTA), is facilitated by systemic administration of nicotine. Pharmacological results show that bursting in VTA-DA cells is critically dependent on a tonic, excitatory amino acid drive, probably originating from the medial prefrontal cortex. Cold inactivation of the prefrontal cortex caused pacemaker-like firing of VTA-DA cells, an effect partly antagonized by systemic nicotine. Clinically, hypofrontality has been associated with negative symptoms in chronic schizophrenia and with chronic alcoholism. Thus, smoking may provide a means to partially restore the dynamics of the VTA-DA system in such disorders. Intravenous nicotine also induces a selective activation of bursting in noradrenaline neurons of the pontine nucleus locus ceruleus. Pharmacological and physiological experiments clearly suggest that this effect is indirect, e.g. peripherally elicited and relayed to the locus ceruleus through its excitatory amino acid input from the paragigantocellular nucleus. The locus ceruleus activation is rapid in onset, dose dependent, short lasting and can be repeated within minutes. This effect of nicotine, which would imply an instant coping response, may be relevant to nicotine dependence, particularly in depressive states. PMID- 2209254 TI - Pharmacokinetic considerations in understanding nicotine dependence. AB - The pharmacokinetic and pharmacodynamic characteristics of a drug are important determinants of whether users become dependent on it and of the temporal patterns of drug use. Characteristics of cigarette smoking, which produces a high degree of dependence, and the use of nicotine gum, which has a relatively low risk of dependence, are compared. Nicotine from tobacco smoke is rapidly absorbed and transferred into the brain. This results in high brain concentrations and intensive psychological effects, with relatively little development of tolerance. The smoker may titrate the level of drug and associated psychological effects of nicotine. Thus, smoking provides a nearly optimal situation for behavioural reinforcement. Chewing nicotine gum results in slow absorption of nicotine, leading to lower levels of nicotine in the brain and substantial time for development of tolerance. Thus, the intensity of effect is less and the onset of effect is delayed from the onset of dosing, providing less opportunity for behavioural reinforcement. Pharmacokinetic and pharmacodynamic modelling techniques have been applied to these processes and used to assess the implications for understanding the daily smoking cycle. PMID- 2209255 TI - Nicotine pharmacodynamics: some unresolved issues. AB - This paper focuses on some issues in the field of nicotine pharmacodynamics in which widely held suppositions have outstripped the supporting evidence. It considers how far the view that nicotine acts as a stimulant in low doses and as a sedative in higher doses is supported by the data and concludes that within the range of doses ingested by cigarette smokers, only stimulant actions have been reliably observed. It examines evidence for the view that nicotine improves ability to sustain attention and concludes that a positive effect of nicotine not attributable to relief of a withdrawal deficit has yet to be demonstrated. Finally, it considers the issue of physiological tolerance and argues that ideas concerning a role for chronic tolerance in nicotine dependence have yet to be supported empirically. Despite advances in our understanding of nicotine's effects in recent years there is still much work to be carried out before fundamental issues underlying its addictive potential can be resolved. PMID- 2209256 TI - Behavioural studies in humans: anxiety, stress and smoking. AB - Numerous observers have reported that smokers smoke more under stressful conditions. The most frequent explanation is that nicotine reduces anxiety, an intervening variable identified as a negative reinforcer for smoking behaviour. The conditions under which anxiety reduction occurs in response to smoking, however, have not been well defined, nor are underlying mechanisms well understood. There are several possible explanations, including Schachter's theory based on stress-induced changes in urinary pH and the hypothesis of endogenous opioid involvement. The work of Collins and his associates in animals has shown that genetic variations in corticosteroid responsiveness to nicotine are associated with differences in sensitivity to nicotine. Research in our laboratory has extended to humans Collins' findings that sensitivity to nicotine is inversely related to corticosteroid activity. We also found that the combination of a psychological stressor and smoking produced additive effects on cortisol release in humans. These findings suggest a novel way of explaining the interaction between smoking and stress, in that increased nicotine intake in the context of stress may in part reflect behavioural compensation for diminished sensitivity to nicotine when corticosteroid activity is enhanced by the stressor. PMID- 2209257 TI - Structural and functional heterogeneity of nicotinic receptors. AB - Three gene families of the ligand-gated ion channel gene superfamily encode proteins which bind cholinergic ligands: (1) nicotinic acetylcholine receptors (AChRs) from skeletal muscle, (2) AChRs from neurons, and (3) neuronal alpha bungarotoxin-binding proteins (alpha BgtBPs). AChRs from muscles and nerves function as ACh-gated cation channels, but alpha BgtBPs do not appear to function in this way. A family of neuronal AChR subtypes has been characterized using monoclonal antibodies and cDNA probes. Neuronal AChRs exhibit sequence homologies with muscle AChRs, but differ in subunit composition, pharmacological and electrophysiological properties, and, in some cases, apparent functional roles. The genes that encode the subunits of the various purified AChR subtypes have been determined in several cases. Histological localization of AChR subunit mRNAs by in situ hybridization and of subunit proteins by immunohistochemistry is being conducted with increasing resolution. The subunit structure of alpha BgtBP is uncertain, but cDNAs have been identified for two subunits. Sequences of these cDNAs reveal that alpha BgtBPs are members of the ligand-gated ion channel gene family, and suggest that they could function as gated cation channels. Biochemical and molecular genetic approaches to studies of neuronal AChRs and related proteins are merging to provide a detailed description of a complex family of AChRs widely dispersed throughout the nervous system, which are probably important to many activities of the nervous system, but whose functional roles are not yet well characterized. PMID- 2209258 TI - Behavioural pharmacology of nicotine: implications for multiple brain nicotinic receptors. AB - Behavioural studies can contribute to the characterization of receptors for psychoactive drugs, and attempts have been made to link behavioural effects of nicotinic agonists with the high affinity binding site for [3H] nicotine. Cueing (discriminative stimulus) effects of drugs enable trained humans or animals to recognize when a specific drug is administered. There was a correlation between the potencies of some compounds in the binding procedure and their ability to produce the nicotine discriminative stimulus in rats, supporting the view that the high affinity binding site was a functional receptor. Nicotine also produced complex changes in locomotor activity of rats, characterized acutely by transient depression and chronically by persistent stimulation. The abilities of nicotinic compounds to produce these locomotor effects were not always consistent with the studies on binding and the nicotine discriminative stimulus. Some compounds were relatively more potent in producing locomotor depression or stimulation than the discriminative effect. Some compounds also failed to produce chronic locomotor activation at doses that produced discriminative and acute depressant effects. These findings may be interpreted as preliminary evidence that different behavioural effects of nicotine may be mediated through different mechanisms, possibly involving multiple subtypes of nicotinic receptors. PMID- 2209259 TI - Mechanism of action of the nicotinic acetylcholine receptor. AB - Nicotinic acetylcholine receptors at peripheral synapses mediate rapid and effective excitatory synaptic transmission. The functional properties of peripheral and central nicotinic acetylcholine receptors are similar, yet in the central nervous system nicotinic receptors do not appear to occur postsynaptically at many excitatory synapses. Two properties of nicotinic receptors are that significant Ca2+ influx can occur through the receptor channel and that at low agonist concentrations steady activation of nicotinic receptors can occur. These are discussed in the context of presynaptic and postsynaptic localizations of nicotinic receptors. PMID- 2209260 TI - Modulation of nicotine receptors by chronic exposure to nicotinic agonists and antagonists. AB - Although numerous studies have demonstrated that chronic nicotine treatment often results in tolerance to this drug, the mechanisms that underlie this tolerance are not well defined. Recent evidence suggests that chronic nicotine treatment results in an up-regulation of brain nicotinic receptors, but the majority of these receptors may be desensitized or inactivated, thereby explaining tolerance. There is evidence that while all mouse strains show increased receptor numbers following chronic nicotine treatment, some mouse strains develop maximal changes in [3H] nicotine binding before any tolerance is detected. Other strains show a high correlation between increase in receptor number and tolerance. Studies with several other nicotinic agonists indicate that up-regulation of nicotine receptors can occur without changes in drug sensitivity. Similarly, chronic antagonists treatment can also elicit changes in receptors without affecting sensitivity to nicotine. Some of these discrepancies may be due to genetically influenced interactions between the adrenal steroid, corticosterone (CCS), and the nicotinic receptors. The addition of CCS in vitro inhibits binding to nicotinic receptors, and chronic CCS treatment results in decreases in the number of brain nicotinic receptors measured by [125I] bungarotoxin binding. Either of these biochemical measures may explain why altering CCS concentrations in vivo results in altered sensitivity to nicotine. It may be that both changes in the number of receptors and altered steroid interactions with the nicotinic receptors explain tolerance to nicotine. PMID- 2209261 TI - [The effects of chlorine disinfection on the resistance of bacteriophage f2 in water]. AB - Under defined conditions, E. coli bacteriophage f2 was subject to repeated disinfection by chlorine 10 times. The survival bacteriophage f2 was compared with its original strain in resistance to chlorine. Experimental results showed that bacteriophage f2 increased its resistance after chlorine disinfection. The increased resistance varied under different conditions. The higher the pH, the greater the increased resistance. The survival bacteriophage f2 maintained its increased resistance though it was passaged 10 times in nutrient broth. The reason for the increased resistance of bacteriophage f2 after chlorine disinfection was probably the chlorine-induced mutation or spontaneous chlorine resistant mutation. PMID- 2209262 TI - [A methodological study on treatment of hospital sewage]. AB - With the view to finding a more effective and economic system for the disposal of hospital sewage, a series of experimental and on the spot investigations were conducted. The results are as follows. Disinfection must be taken as the key link in the treatment of hospital sewage. After primary treatment and chlorination, when the product value of concentration (mg/L) multiplied by time (min.) achieved to 240 (general hospital) and 540 (tuberculosis hospital), the content of suspended substances (SS) fell to 37 mg/L; the clearance rate of SS reached 82%. The BOD5 fell to 35 mg/L a drop to 42%. E. coli was less than 9 individual/L, the killing rate reached 99.999 99%. The intestinal pathogens and tubercle bacillus were completely wiped out. The sludge from the sewage can be treated with lime [Ca(OH)2] and when the pH value rose to 12, the requirement of disinfection was satisfied and both the sludge and sewage can be drained. The aeration of sewage through shooting flow, biological oxidation combined with sediment action by passing thru reclining tubes is an effective way for the secondary treatment of hospital sewage. In addition, we developed the double siphon equipment with water power-automatic controller, the WD-700 flowmeter, the anti-corrosive paint coating the contact pond; according to test parameters, we designed a simplified evaluation graph for the purpose of surveillance. PMID- 2209263 TI - [The dispersion and allergenicity of the airborne pollen in Nanjing]. AB - This paper presents the results of a two-year study on the dispersion and allergenicity of the airborne pollen in Nanjing. We found 28 families of pollen of plant dispersing in the city. Seventeen species of commonly seen pollen grouped under twelve families were collected and their pollen extracts were used for skin test in the 219 cases of bronchial asthma. The results showed the mode of dispersion of air-borne pollen and the main families of allergic pollen being the Moraceae' Cupressaceae platanuceae and Julandaceae in spring and the gramineae Compositae Chenopodiaceae and Cannabinaceae in autumn. This information provides a firm basis in the prevention diagnosis and treatment of allergic diseases in the area of Nanjing. PMID- 2209264 TI - [A study of relationship between plasma testosterone and body fat in normal boy adolescents]. AB - The plasma testosterone and the skinfolds of eight sites of the body were measured in 127 normal boy adolescents, aged 9-15, and the percentage of body fat (%BF), lean body mass (LBM), total body fat (TBF) were calculated from subscapular and triceps skinfolds. The results showed: with the increasing of plasma testosterone, the changes of distributive pattern of skinfolds, thickners was not uniform and the correlation of testosterone was positive with TBF (r = 0.252 2) and LBM (r = 0.588 7), negative with %BF (r = -0.222 3). PMID- 2209265 TI - [Protective effects of vitamin E and selenium on myocardial mitochondria in rats- a study on the pathogenic factors and pathogenesis of Keshan disease]. AB - The protective effects of vitamin E (VE) and selenium (Se) on myocardial mitochondria were investigated in rats fed grains (with 0.006 ppm Se) from an endemic area of Keshan disease. The results indicated that supplementing the endemic grains with VE or Se (in 150 ppm and 0.1 ppm respectively) elevated, in different degrees, the depressed activities of four myocardial mitochondrial complexes of electron transport, of which the activity of complex II was increased significantly (P less than 0.05). In addition, the activity of Mn- superoxide dismutase was increased and the content of lipid peroxides was decreased in the myocardial mitochondria of rats of both groups with the supplements. The study shows that VE and Se protect the myocardial mitochondria from damage induced by lipid peroxidation in the rats fed grains from Keshan disease endemic areas. PMID- 2209266 TI - [A study of left ventricular function of workers exposed to fluorine]. AB - The left ventricular function of 26 workers exposed to fluorine was investigated. The results demonstrated that the LVET in the higher urine fluorine group (greater than 1.5 mg/L) was significantly shorter than the control group (P less than 0.01), the PEP was much longer than the control group (P less than 0.05), and the rate of PEP/LVET compared with the control group was increased. The difference was statistically significant (P less than 0.01). In the lower urine fluorine group (less than 1.5 mg/L) the time of LVET and PEP and the rate of PEP/LVET was not significantly different from the control group. The results showed that excessive fluorine ion in the body could cause decrease of myocardial contraction. The reason may be, that the fluorine ion inhibits the activities of certain enzymes in the body, thereby producing inhibition of ATP supply and utilization. PMID- 2209267 TI - [Effects of benzo(a)pyrene on the humoral immunity of mice exposed by single intraperitoneal injection]. AB - Mice were exposed to benzo(a)pyrene at a dosage of 50, 100 and 200 micrograms/g by single intraperitoneal injection route. The control mice were given vehicle alone (olive oil). The mice were killed 5 days later. At above dosage, it was found the body weight, thymus and spleen weights, and the leukocyte count in peripheral blood were significantly reduced as compared to control. In the plaque forming cell (PFC) assay, it was also found the IgM antibody forming response to the thymus independent antigen (TNP-Ficoll) and the thymus dependent antigen (TNP KLH) were inhibited about 57-94% and 58-80%, respectively, (P less than 0.05). The serum anti-TNP-Ficoll antibody titer was suppressed 46-98% and parallelled to the corresponding spleen PFC response. The results suggested the benzo(a)pyrene or its metabolites may directly affect the more matured B lymphocyte's function. PMID- 2209269 TI - [Current status of the use of domestic hematologic hepatitis B vaccine]. PMID- 2209268 TI - [Proton inducted X-ray emission analysis of food samples]. AB - PIXE (Proton inducted X-ray emission) analysis of food samples was carried out with 2 Mev protons. The measured seven trace elements for 62 food samples are listed in tables. PMID- 2209270 TI - Preoperative radiotherapy in operable rectal cancer. AB - The effect of preoperative radiotherapy (31.5 Gy in 3.5 weeks) in operable rectal cancer was examined with respect to resectability and prognosis after two surgical procedures, abdominoperineal resection, or low anterior resection. Preoperative radiation did not influence the surgeon's selection of low anterior resection, which was similar (40 percent) in each group. Radiation improved five year survival probability and decreased the incidence of local recurrence significantly after low anterior resection. In contrast, no improvement of treatment results was found in patients treated by abdominoperineal resection after radiotherapy. PMID- 2209272 TI - The freckle sign--an endoscopic feature of the cecum. AB - Mucosal spots, or "freckles," surrounding the appendiceal orifice are an endoscopic feature of the cecum. These are clusters of 1 to 2 mm round or oval slightly raised spots, each with a pale center and an erythematous border. They correlate microscopically with subepithelial and submucosal lymphoid follicles. The freckling pattern, identified in about one third of colonoscopies, was seen best with the videoendoscope and was identified more commonly in patients with systemic illness. Recognition of mucosal freckling around the appendiceal orifice helps identify the cecum and may be useful in the evaluation of cecal and appendiceal pathology. PMID- 2209271 TI - Absorption and motility of the bypassed human ileum. AB - The authors assessed absorption and motility of the human ileum after a prolonged period of disuse. In eight patients with ulcerative colitis, a manometric catheter assembly was placed via the ileostomy into the unused portion of distal ileum two months after ileal pouch-anal anastomosis and temporary diverting loop ileostomy. The distal ileum was perfused at 5 ml/min with an isosmotic solution of either sodium chloride or ileal chyme diluted with sodium chloride for three hours before and three hours after a meal on two consecutive days. Absorption was measured, single and clustered pressure waves were identified and quantitated with the aid of a computer program, and a motility index was calculated. Mean absorption +/- S.E.M. of both perfusates was poor on day 1 (-10 +/- 2 ml/25 cm x 30 min), and the meal induced no ileal motor response. By day 2, however, absorption of both perfusates was much improved (-1 +/- 2 ml/25 cm x 30 min; P less than 0.05), and the number of discrete clustered contractions and the motility index now clearly increased after the meal (2.6 +/- 0.6 vs. 7.2 +/- 1.0 clustered waves/hr; 7.5 +/- 0.5 vs. 9.7 +/- 0.2 motility units/30 min; P less than 0.05). The conclusion was that absorption and motility of the human ileum were impaired after two months of disuse, but that ileal absorption and motility improved one day after the introduction of isosmotic ileal perfusates. PMID- 2209273 TI - Relationship between blood plasma prostaglandin E2 and liver and lung metastases in colorectal cancer. AB - The relationship of prostaglandin E2, of which a large amount is produced in various neoplasms, and hematogenous distant metastases was investigated in a total of 44 colorectal cancer patients because of its varied pathophysiologic potentials. The authors found significantly high levels of PGE2 in local venous blood draining the carcinoma and in peripheral blood in cases with liver or lung metastasis, as well as a significantly large amount of PGE2 production in the carcinoma tissue. The results suggest that increased local blood PGE2 could enhance the metastasis formation, and increased peripheral blood PGE2 may be useful in the detection of such metastasis in colorectal cancer. PMID- 2209274 TI - Rectal bleeding. Patient delay in presentation. AB - Patient delay in presentation of rectal bleeding has been identified as a factor in delayed diagnosis among patients with colorectal cancer. The aim of this study was to identify demographic or psychological factors, or beliefs or behaviors related to delay in presentation of rectal bleeding. In 93 patients presenting with this symptom to their general practitioner, delay ranged from 0 to 249 days with a median of 7 days; 27 (29 percent) delayed more than 14 days. Delay was unrelated to age, sex, ethnic origin, competence in English, length of schooling, social status, availability of social support, measured psychologic traits, and to the belief that the cause might be cancer. The proportions delaying more than 14 days were statistically significantly elevated among those who were not worried by the bleeding (47 percent delayed); those who did not regularly look at their feces or the toilet paper after use (37 percent); and those who took some other action before presenting to their general practitioner (43 percent). PMID- 2209275 TI - The starved colon--diminished mucosal nutrition, diminished absorption, and colitis. AB - Nutrition of colonic epithelial cells is mainly from short chain fatty acids (SCFAs) produced by bacterial fermentation in the colonic lumen. n-Butyrate contributes more carbon of oxidation to epithelial cells than glucose or glutamine from the vasculature. Incomplete starvation of colonic epithelial cells through lack of luminal SCFAs leads, in the short term, to mucosal hypoplasia with either diminished absorption or diarrhea. A chronic lack of SCFAs or complete organ starvation in conjunction with other factors leads to nutritional colitis, either "diversion colitis" or "starvation colitis." Whether predominantly diarrhea or colitis develops in mucosal malnutrition appears to depend upon the severity and duration of starvation. Ulcerative colitis may be classified as a nutritional colitis in that colonic epithelial cells are unable to utilize SCFAs reflecting epithelial starvation despite abundant SCFAs. PMID- 2209276 TI - Endosonography of pararectal lymph nodes. In vitro and in vivo evaluation. AB - One hundred thirteen patients with carcinoma of the rectum were evaluated for lymph node metastases by endorectal ultrasound. With the use of 7.5 MHz and based on different echo patterns, two main groups of lymph nodes can be differentiated: hypoechoic and hyperechoic lymph nodes. Compared with pathologic findings, hypoechoic lymph nodes represent metastases, whereas hyperechoic lymph nodes are visualized due to unspecific inflammation. Lymph node metastases can be predicted with a sensitivity of 72 percent and inflammatory lymph nodes with a specificity of 83 percent. The physical basis of the differentiation of lymph nodes was assessed in vitro by the determination of ultrasound parameters (speed of sound, acoustic impedance, attenuation, and backscattered amplitude). The attenuation coefficient of benign lymph nodes [2.5 dB/(MHz x cm)] is significantly higher than the mean value of lymph node metastases [1.3 db/(MHz x cm)]. The results demonstrate that involved nodes can principally be differentiated from not involved nodes. Micrometastases, mixed lymph nodes, and changing echo patterns within inflammatory nodes explain the accuracy rate of 78 percent. PMID- 2209277 TI - Crohn's disease and pregnancy. AB - Seventy-eight pregnancies in 50 patients were reviewed to evaluate the effects of Crohn's disease on the outcome of pregnancy and the influence of the pregnancy on the course of Crohn's disease. Overall, 21 pregnancies (27 percent) had abnormal outcomes including spontaneous abortions (9), infants small for gestational age (6), premature infants (5), and infants who developed respiratory distress (1). Eight (50 percent) patients with active disease compared with 13 (21 percent) patients with inactive disease at conception had abnormal outcomes (P less than 0.05). During pregnancy 15 (55 percent) with active disease and 6 (12 percent) with inactive disease had an abnormal outcome (P less than 0.001). Neither medical nor surgical treatment, independent of disease activity, appeared to affect the outcome adversely. Eighteen of 73 (25 percent) patients with quiescent or mild disease relapsed, and seven of 16 patients with some disease activity improved (44 percent). Of 34 patients on medication, nine relapsed (27 percent), and of 39 patients not on medication, nine relapsed (24 percent) (P = N.S.). These results suggest that the outcome of pregnancy is not adversely affected by Crohn's disease. However, patients with active disease at conception and/or during the pregnancy have poorer outcomes independent of the use of medication or requirement of surgery. Neither pregnancy nor medications taken affect the course of the disease. PMID- 2209279 TI - Reversed intestinal rotation associated with anomalous mesenteric venous drainage. Report of a case. AB - Reverse intestinal rotation is a congenital abnormality of midgut rotation. Mesenteric arterial, venous, and lymphatic compression may occur, but associated anomalous mesenteric venous drainage is extremely rare. The case presented illustrates the importance of recognition of intestinal malrotation and the danger of bowel resection in the presence of anomalous mesenteric venous drainage. PMID- 2209278 TI - Short-term chemoprophylaxis with ceftizoxime vs. five-day aminoglycoside with metronidazole in 'contaminated' lower gastrointestinal surgery. AB - In a prospective, open, randomized controlled trial, 173 patients requiring surgery for potentially "contaminated" lower gastrointestinal surgery were allocated to receive either two doses of ceftizoxime (2 gm) with one dose of metronidazole (1.5 gm) or gentamicin 3 mg/kg/day for five days with one dose of metronidazole (1.5 gm). Eighty-nine patients received ceftizoxime and 84 patients received gentamicin. The groups were comparable with respect to diagnosis, procedure, type of anastomosis, and wound closure. The incidence of withdrawal due to failure to respond to the study drug (11.5 percent) was equivalent in the two groups. There was no difference in the overall incidence of postsurgical infection between the ceftizoxime and metronidazole group (22.2 percent) and the gentamicin and metronidazole group (25.7 percent). The incidence of wound infection (ceftizoxime and metronidazole, 6.9 percent; gentamicin and metronidazole, 10 percent) and deep sepsis (ceftizoxime and metronidazole, 15.3 percent; gentamicin and metronidazole, 15.7 percent) was similar. PMID- 2209280 TI - Gastrointestinal tuberculosis. Report of four cases. AB - Gastrointestinal tuberculosis is a rare disease in the United States. Correct identification is often delayed because it is not considered early on in the differential diagnosis. Four patients with gastrointestinal tuberculosis and the symptoms, diagnosis, complications, and treatment of the disease are discussed. Gastrointestinal tuberculosis should be considered in Asian immigrant patients who present with symptoms and signs of inflammatory bowel disease. PMID- 2209281 TI - Healing of experimental intestinal anastomoses. Parameters for repair. AB - Anastomotic dehiscence remains a major complication in surgery of the large bowel, and studies on the healing sequence of experimental anastomoses are necessary to define underlying mechanisms and find ways to improve surgical outcome, particularly in high-risk situations. For the quantitative description of anastomotic repair, both mechanical and biochemical parameters are employed, each with their own limitations. Mechanical parameters, either bursting pressure or breaking strength, only reflect growing anastomotic strength as long as disruption occurs within the anastomotic area, which is less than one week after surgery for the bursting pressure and probably up to two weeks for the breaking strength. The biochemical description of anastomotic repair has been limited to behavior of collagen, as represented by its rather unique constituent amino acid hydroxyproline. Conclusions based on collagen concentrations--per unit weight- should be considered with caution since they may change as a consequence of changes in noncollagenous substances. In this respect, collagen content, per unit length, is probably a better parameter to describe anastomotic collagen levels. Few investigations have addressed the quality of collagen (e.g., crosslinking or type). Since, at this time, no distinct correlations have been demonstrated between development of mechanical strength or occurrence of leakage and collagen levels in the healing anastomosis, attention should not be restricted to a description of the quantity of collagen present: the quality of anastomotic collagen should be investigated, perhaps even more so. PMID- 2209282 TI - Foreign body removal through an appendicostomy. AB - The removal of button cell batteries or small coins impacted in the terminal ileum or right colon through an appendicostomy is described. This technique was used effectively in three patients. PMID- 2209283 TI - Surgical treatment of circumferential hemorrhoids. PMID- 2209284 TI - A safe technique for resection of perforated sigmoid diverticulitis. PMID- 2209285 TI - Barrett's esophagus in children and young adults. Frequent association with mental retardation. AB - Since few data are available on epidemiologic features of Barrett's esophagus in young persons, we reviewed the case records of patients undergoing esophageal biopsies at Children's Hospital, Boston, from 1982 through 1986. There were 1423 esophageal biopsies obtained from 1173 patients, and histological evidence of esophagitis was present in 397 cases; Barrett's epithelium was diagnosed in 10 patients (0.9% of total and 2.5% of esophagitis cases). Specialized columnar epithelium was present in seven of these 10 patients. The mean age of those with Barrett's epithelium was 19.0 +/- 7.9 years (range 3.7-27 years) compared to 8.7 +/- 6.7 years (range 4 days to 31 years) for all patients biopsied (P less than 0.0001); 80% (8/10) of the Barrett's cases were male compared to 54% of all cases. The relative importance of the possible risk factors was assessed by comparing the 10 patients with Barrett's with the 541 patients that had esophageal biopsies in calendar years 1984-1985. Mental retardation, a risk factor not previously described for young persons with Barrett's esophagitis, was present in 70% (7/10) of the Barrett's patients but in only 15% of all patients biopsied (P less than 0.0002). The frequency of mental retardation was also higher, but not significantly so (P greater than 0.07), in patients with biopsies that were positive for esophagitis (19%) than in those with normal biopsies (14%). No significant differences were found between the Barrett's group and all patients biopsied in regards to racial origin, prior stricture, or fundoplication. PMID- 2209286 TI - Twenty-four-hour pattern of esophageal motility in asymptomatic volunteers. AB - Diurnal variations in the pattern of esophageal motility and acidity were studied in 14 healthy volunteers. Data from a two-channel manometry and one-channel pH metry recording were stored in a portable 1-MByte, solid-state data logger for subsequent computerised analysis. Comparison of predefined nighttime, mealtime and nonmeal daytime periods showed that propagated contractions predominated during mealtimes (56% of all contractions) and nonmeal daytime periods (53.5% of contractions) and that their propagation velocity (2.98 cm/sec) was at its lowest and the AUC of all contractions (134.6 hectoPascal.sec) at its greatest during mealtime periods. During the night, propagated contractions (0.136/min) and simultaneous contractions (0.025/min) were significantly less frequent than during both meal (1.31/min and 0.172/min, respectively) and nonmeal daytimes (0.665/min and 0.133/min, respectively), whereas the nocturnal segmental contraction frequency (0.181/min) was not significantly lower than the nonmeal daytime contraction frequency (0.243/min). Median reflux time was in the normal range (1.2%), although two subjects had prolonged reflux times (9.5% and 14.5%). In conclusion, all subjects showed similar patterns of diurnal esophageal contractory activity determined partly by meal intake and partly by a characteristic clustering of nocturnal contractions that could not be explained by episodes of nocturnal gastroesophageal reflux. It may, therefore, be speculated that nocturnal contraction clusters are associated with rhythmic phenomena such as MMC or specific sleep stages. PMID- 2209287 TI - Scintigraphic measurement of oropharyngeal transit in man. AB - Scintigraphic studies of the oropharyngeal transit of a liquid bolus were performed in 15 healthy controls, 12 patients with symptoms of oral-pharyngeal dysphagia, and 13 patients with neuromuscular disease, who did not have dysphagia. Gamma camera imaging of the head, neck, and upper thorax was undertaken, in the lateral projection, during the swallowing of the radiolabeled bolus of water. Inspection of summed images permitted the selection of regions of interest (ROI) to represent the mouth, pharynx, and upper esophagus. Transit times between each ROI were calculated and compared. Significant prolongation of bolus transit time between the mouth and esophagus was present in both patients with and without dysphagia (0.59 +/- 0.38 sec and 0.33 +/- 0.7 sec; mean +/- SD, respectively) compared with controls (0.26 +/- 0.04 sec P less than 0.001, P less than 0.01, respectively, Mann-Whitney U test). Repeat studies in 25 individuals indicated that the transit measurements were more reproducible between swallows in normal subjects than in patients with symptoms. Deglutitive scintigraphy provides a noninvasive technique for the quantitative study of swallowing and its disorders. PMID- 2209288 TI - Drug-induced esophageal injury. Histopathological study in a rabbit model. AB - The purpose of this animal study was to investigate the histopathologic consequences of esophageal exposure to a variety of medications known to be injurious to the human esophagus. Twenty-four New Zealand white rabbits were utilized. Tablets or control plastic beads were secured to a silk suture thread and positioned in the rabbit esophagus through a proximal esophagostomy and a gastrostomy. Test medications were allowed to dissolve passively on the surface of the esophageal mucosa in the anesthetized rabbits. After 1 hr of drug exposure, the rabbits were killed and the esophagus removed and examined. No gross abnormalities were detected with the exception of a mild degree of erythema at some of the exposure sites. All medications and control beads produced microscopic mucosal changes when compared to suture controls. The beads and test medications caused thinning of the epithelium and increased subepithelial edema (P less than 0.05). Two changes, however, were unique to animals exposed to test medications: fraying and/or splitting of the epithelium and the presence of balloon cells (P less than 0.05). Balloon cells represent damaged squamous epithelial cells recognizable by their distended, globoid shape. The prevalence of balloon cells ranged from 22% to 89% of sites exposed to drug and was most commonly associated with potassium. Of all drugs reported to cause injury to the human esophagus, potassium chloride has been reported to produce the most severe lesions, including esophageal stricture and perforation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2209289 TI - Cell isolation and genotoxicity assessment in gastric mucosa. AB - It has been claimed that in vitro digestion of in vivo DNA-labeled gastric mucosa is suitable for evaluation of genotoxic effects of drugs or chemicals. This method was then used to show that omeprazole (a novel antiulcer drug) was potentially genotoxic. In this study we have examined the method used and the interaction of omeprazole and its derivatives with purified DNA. The method was shown to enrich for dividing cells (6.92 +/- 0.693%, N = 43, 2-hr labeling) in the digest from the intact tissue and was therefore unsuitable for estimating unscheduled DNA synthesis in the gastric mucosa induced by chemicals or drugs including omeprazole. It was further shown that neither omeprazole or its acid activated product, a cationic sulfenamide, were able to react with isolated purified DNA from either a prokaryote (E. coli) or a eukaryote (salmon sperm). Hence any conclusions using this method attributing acute genotoxic effects to any chemical are based on unrecognized artifacts of the technique and are unsound. In addition, these results negate the suggestion that omeprazole or its gastric metabolites are genotoxic. PMID- 2209290 TI - Gastric dysrhythmias following pylorus-preserving pancreaticoduodenectomy. Possible mechanism for early delayed gastric emptying. AB - Transient delayed gastric emptying is reported as a frequent complication following pancreas-preserving pancreaticoduodenectomy (PPW). We placed serosal electrodes on the stomach of a patient undergoing PPW. Myoelectric recordings were obtained postoperatively and correlated with simultaneous radionuclide liquid gastric emptying studies. The patient developed early postoperative gastric atony, associated with frequent gastric dysrhythmias. These dysrhythmias may have been exacerbated by a perihepatic abscess. The gastric dysrhythmias correlated with alterations in liquid gastric emptying. Gastric dysrhythmias may be a mechanism for gastric dysfunction in the early postoperative period. PMID- 2209291 TI - Sterol-dependence of gastric protective activity of unsaturated phospholipids. AB - The major aim of this study was to investigate the gastric protective effect of unsaturated phospholipids and to determine the ability of neutral lipids to enhance this activity. We found that although a liposomal suspension of unsaturated phosphatidylcholine (PC) administered intragastrically failed to protect rats from acid-induced gastric ulcer formation, addition of cholesterol to unsaturated PC induced a dose-dependent protective response with the maximally effective dose, reducing lesion score greater than 70%. This effect also was seen with the plant sterol, beta-sitosterol (reducing lesion score by 81.6 +/- 36%) but was blocked if cholesterol was esterified to fatty acids of varying chain length. Addition of sterols to liposomes of saturated dipalmitoylphosphatidylcholine, in contrast, attenuated the gastric protective action of the saturated PC. It appears that the protective mechanism elicited by sterols and unsaturated PC is not mediated by alterations in gastric emptying rate or prostaglandin biosynthesis, although maintenance of surface hydrophobicity may be involved. These results suggest that the sterol may promote the packing of adjacent unsaturated phospholipid molecules of either the cell membrane or a putative extracellular hydrophobic lining of the gastric epithelium to provide the mucosa with protection against luminal acid. PMID- 2209292 TI - Gastric lesions secondary to long-distance running. AB - Gastrointestinal disorders have been reported during long-distance running. The purpose of this study was to evaluate the effects of prolonged exercise on the upper digestive tract. Seven subjects were submitted to a standard endoscopic examination of the upper digestive tract before and after long-distance running (range 18-50 km). Mucosal biopsy specimens were taken during all endoscopies. After running, all runners had histologically pathological features in the stomach. Vascular lesions were present in the chorion in six subjects after running, with the intensity of the lesions ranging from congestion to hemorrhage. Postexercise histological examination also showed a decrease in mucosal secretion. These lesions secondary to prolonged exercise indicate the presence of hemodynamic perturbations in the upper digestive tract. PMID- 2209293 TI - Effects of dietary protein alterations on circadian rhythms of gastrointestinal peptides in rats. AB - Altered protein diets and circadian rhythms of gastrin and cholecystokinin (CCK) were investigated in 126 male and 126 female Sprague-Dawley rats acclimated for two weeks to a 12:12 hr light-dark cycle. Rats were divided equally and fed low protein (8%), high-protein (64%) or normal protein (27%) diets for four weeks. All animals were fasted for 24 hr prior to blood collections. Blood samples were collected at 4-hr intervals for 24 hr for determination of plasma gastrin and CCK using specific radioimmunoassays. A significant rhythm for gastrin was detected in males on normal and low-protein diets (P less than 0.03) and in females on low protein diets (P less than .02). A significant rhythm for CCK was detected (P less than 0.05) in rats of both sexes fed normal and high-protein diets. Mean plasma levels of both peptides were lower in females than males. In a separate study, food intake and body weight were monitored in male rats receiving the three diets over 21 days. Animals on the low-protein diet exhibited reduced food intake and body weight compared to rats fed the normal or high-protein diets. PMID- 2209294 TI - Behavioral modification of colonic function. Can constipation be learned? AB - We challenged the two hypotheses: first, that defecation can be suppressed for an extended time, and second, if so, that this has an effect on upper colonic motility. Thus we studied 12 male volunteers with conditions of identical nutrition and patterns of physical activity over a two-week period, where one week with normal defecation and one week with voluntary prolonged suppression of defecation followed each other in randomized order. Frequencies of defecation, stool weights, total and segmental colonic transit times (using radiopaque markers) were compared. Frequency of defecations and stool weights were lower during suppressed defecation [8.9 +/- 0.66 vs 3.7 +/- 0.41 (mean +/- SE) bowel movements per week, P = 0.003, and 1.30 +/- 0.09 vs 0.98 +/- 0.13 kg/week, P = 0.01]. Total transit times were increased from 28.8 +/- 4.4 to 53.1 +/- 4.3 hr, P = 0.004. Segmental transit times were increased in the rectosigmoid (from 8.83 +/ 3.6 to 32.1 +/- 5.6 hr, P = 0.04) and right hemicolon (from 14.5 +/- 0.9 hr to 19.7 +/- 1.5 hr, P = 0.02) by suppression of defecation. We conclude that defecation habits may induce changes in colonic function such as those seen in constipation and that functional anorectal outlet obstruction may, probably by reflex mediation, affect the right colon. PMID- 2209295 TI - Outpatient health care utilization of patients with inflammatory bowel disease. AB - On the basis of the normal life expectancy of inflammatory bowel disease patients, the early onset of their disease, and the variety of symptoms, inflammatory bowel disease patients were anticipated to be frequent users of outpatients services. This study assesses (1) the characteristics, (2) outpatient health care utilization, and (3) the degree of satisfaction with health care of inflammatory bowel disease patients compared to patients with other gastrointestinal disease. The study method was a secondary analysis of data collected on 395 patients attending the University of Calgary Gastroenterology Outpatient Clinic in 1988. Inflammatory bowel disease patients were significantly younger (P less than 0.001) and better educated (P less than 0.05) than other patients. During the past year inflammatory bowel disease patients consulted significantly more often with their gastroenterologist (P less than 0.001) and spent more time in hospital (P less than 0.05) than other patients. Inflammatory bowel disease patients also consulted more frequently with herbalists and naturopaths. Lastly, inflammatory bowel disease patients were as satisfied with the health care they received as other patients. These results provide information useful for health care planners as well as for those dealing directly with inflammatory bowel disease patients. PMID- 2209296 TI - Investigation of mode of action of biofeedback in treatment of fecal incontinence. AB - A study was carried out in 25 incontinent patients to evaluate some of the factors thought to be responsible for the success of retraining for fecal incontinence. Subjects were initially allocated to one of two groups; one group was trained to perceive small rectal volumes (active retraining), the other group carried out the same maneuvers but were not given any information or instruction. Active sensory retraining reduced the sensory threshold from 32 +/- 8 to 7 +/- 2 ml (P less than 0.001), corrected any sensory delay that was present (P less than 0.004), and reduced the frequency of incontinence from 5 +/- 1 to 1 +/- 1 episodes per week (P less than 0.01). Sham retraining caused a modest reduction in the sensory threshold (from 29 +/- 9 to 20 +/- 8; P less than 0.05) but did not significantly reduce the frequency of incontinence. Subsequent strength and coordination training did not significantly improve continence, although at the end of the study, 50% of patients had no incontinent episodes at all and 76% of patients had reduced the frequency of incontinence episodes by more than 75%. This improvement in continence was not associated with any change in sphincter pressures or in the continence to rectally infused saline but was associated with significant improvements in rectal sensation. The functional improvement was sustained over a period of two years in 16 of the 22 patients available for follow-up. In conclusion, the results support the use of retraining in the management of fecal incontinence and suggest that retraining may work by enhancing rectal sensitivity and instilling confidence. PMID- 2209297 TI - Pepsin and the gastric mucus barrier. PMID- 2209298 TI - Lack of cutaneous hyperemia in response to insulin-induced hypoglycemia in IDDM. AB - Cutaneous blood flow was measured with the laser Doppler technique and by recording cutaneous O2 tension on the forearm and forehead in nine young adult patients with insulin-dependent diabetes mellitus (IDDM) and nine sex- and age matched healthy control subjects after induction of hypoglycemia. In the healthy subjects, cutaneous blood flow measured with the laser Doppler technique was increased by 120 +/- 26% in the forehead (P less than 0.01) and 196 +/- 50% in the forearm (P less than 0.01) at the glucose nadir (blood glucose 1.8 +/- 0.2 mM) compared with basal blood flow. In contrast, in diabetic patients, cutaneous blood flow was unchanged. The corresponding changes, at the glucose nadir, with cutaneous O2 tension recordings were 286 +/- 131% (P less than 0.05) in control subjects and -22 +/- 15% (NS) in diabetic patients. An impairment of sympathetic nervous function, not detectable by simple cardiovascular tests, could be responsible for the lack of cutaneous hyperemia and sweating and could contribute to unawareness of hypoglycemia in diabetic patients. PMID- 2209299 TI - Is menarche associated with diabetic retinopathy? AB - The goal of this study was to evaluate the association between menarchal status and diabetic retinopathy. Diabetic retinopathy was present in 51 of 129 females; 7 were premenarchal, and 44 were postmenarchal. The range of severity of retinopathy was greater in the postmenarchal group. In multivariate analyses, duration of diabetes, menarchal status, and diastolic blood pressure were associated with the prevalence of diabetic retinopathy. After partitioning the duration of diabetes into years before and years after menarche, both were significant, but the number of years of diabetes after menarche was more strongly associated. At a 4-yr follow-up examination, more postmenarchal than premenarchal females had progression of their retinopathy (P = 0.06). These data suggest that stage of sexual development, as reflected by menarchal status, is associated with the presence and possibly the risk of progression of diabetic retinopathy. PMID- 2209300 TI - Randomized crossover study of effect of resistance training on glycemic control, muscular strength, and cholesterol in type I diabetic men. AB - The goal of this study was to evaluate a program of resistance weight training on cardiovascular risk factors, blood glucose management, and overall strength in diabetic subjects. A randomized crossover design was performed on eight male type I (insulin-dependent) diabetic subjects (mean +/- SD age 31 +/- 3.5 yr, height 176 +/- 5.6 cm, body wt 80 +/- 15 kg, duration of diabetes 12.3 +/- 9.8 yr, and insulin dose 24 U NPH/day and 21 U regular/day). The program consisted of heavy resistance weight training 3 days/wk for 10 wk, concentrating on the strengthening of major muscle groups through progressive resistance. Blood tests included total cholesterol, triglycerides, very-low-density lipoprotein and high density lipoprotein cholesterol, and HbA1c. These tests were repeated at three time points during the program. Field-strength testing was performed before and after training. An improvement was seen in the squat (93.6% increase, P less than 0.0001) and bench press (58% increase, P less than 0.005). HbA1c and triglyceride levels showed no change during the resting portion of the experiment but showed a significant change with the training program: HbA1c 6.9 +/- 1.4 vs 5.8 +/- 0.9% (P = 0.05) and triglyceride 5.044 +/- 1.06 vs. 4.628 +/- 0.88 mM (P = 0.01). Self monitored glucose (taken pre- and postexercise) showed a decrease from 7.85 +/- 3.13 to 7.05 +/- 2.91 mM (P = 0.0001). Very-low-density lipoprotein cholesterol and triglycerides did not change after training. Analysis of variance showed no significant differences over time from the three time points with regard to reductions in cardiovascular risk factors or HbA1c.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2209301 TI - Incidence of IDDM during 1984-1986 in population aged less than 30 yr. Residents of Turin, Italy. AB - The goal of this study was to measure the incidence of insulin-dependent diabetes mellitus (IDDM) during 1984-1986 in residents of Turin, Italy, aged less than 30 yr. The primary data source was the list of all subjects diagnosed with IDDM who attended diabetes clinics in Turin. Other data sources were the general register of death certificates, the list of hospital discharges, and the computerized data base of insulin prescriptions. Eighty incident cases of IDDM were identified during the study in 1,130,284 person-yr for those less than 30 yr of age. Age adjusted (world standard) incidence rates were 8.05, 8.10, and 6.96/100,000 in the age-groups 0-14, 0-19, and 0-29 yr, respectively. Estimated completeness of the primary data source compared with all other data sources was 91%, whereas the estimated completeness of ascertainment of the registry was 99%. Incidence rates of IDDM in northern Italy compare with those of European countries with low medium incidence. A population-based register is being established for the province of Turin (951,445 inhabitants aged 0-29 yr) for the collection of incident cases since 1984. PMID- 2209303 TI - WHO Multinational Project for Childhood Diabetes. WHO Diamond Project Group. AB - Insulin-dependent diabetes mellitus (IDDM) is one of the most important chronic diseases of children worldwide. IDDM leads to an 8- to 10-fold excess risk of mortality in developed countries, whereas in developing countries, most cases die within a few years. A 60-fold international gradient in IDDM incidence has been reported, and epidemic periods have been identified. A new World Health Organization program, Multinational Project for Childhood Diabetes (Diabetes Mondiale or DIAMOND), has been developed to investigate and characterize global incidence, mortality, and health care. Over 10 yr (1990-1999), this study will collect population-based data concerning IDDM in greater than 90 centers in 50 countries worldwide. The goals of DIAMOND are to collect standard information on incidence, risk factors, and mortality associated with IDDM; evaluate the efficiency and effectiveness of health care and the economics of diabetes; and establish national and international training programs in diabetes epidemiology. It is hoped that the DIAMOND project will be instrumental for the prevention of this serious disease and its sequelae. PMID- 2209302 TI - Comparison of quantitative sensory-threshold measures for their association with foot ulceration in diabetic patients. AB - We compared the accuracy of cutaneous pressure perception-threshold measurements with that of other sensory-threshold measurements for detecting diabetic foot ulcer patients. Three hundred fourteen non-insulin-dependent diabetic patients were studied, of whom 91 had either a current foot ulcer or a history of foot ulceration. Foot ulcer patients had much higher pressure perception thresholds at the hallux than those without foot ulcers (mean +/- SE 4.63 +/- 0.05 vs. 3.54 +/- 0.04 U, P less than 0.001). The magnitude of association was higher than that for vibration thresholds and markedly greater than those for cool and warm thresholds. Pressure thresholds were highly accurate for identifying foot ulcer patients. At a threshold level of 4.21 U, the sensitivity was 0.84, with a specificity of 0.96. At similar sensitivities for vibration and thermal thresholds, specificities were lower. Foot ulceration and cutaneous pressure perception threshold are strongly associated. Pressure-threshold measurements are extremely accurate and perform at least as well as other quantitative sensory tests in identifying foot ulcer patients. Assessment of the foot pressure threshold may have promise as a simple and inexpensive method for detecting diabetic patients at risk for foot ulcers. PMID- 2209304 TI - Evaluation of new rapid office test for microalbuminuria and its comparison to fully quantitative radioimmunoassay. AB - A novel enzyme-linked immunosorbent assay (ELISA [Dialbumin]) for rapid office measurement of microalbuminuria was evaluated and its performance compared with that of a commercially available radioimmunoassay (double-antibody albumin). Urine samples containing between 0.75 and 1800 micrograms/ml of albumin were obtained from 31 diabetic patients and assayed by both methods. A comparison of the paired values obtained from the two methods gave a correlation coefficient of greater than 0.99. The Dialbumin assay, which used detachable eight-well strips (1 strip/sample), 10-min incubation, tap water wash, and a 2-min color development step, was read on both an ELISA reader and a hand-held analytical device (Acc-U-Dial) designed specifically for this test. The findings of this study indicate that the Dialbumin assay, used in conjunction with the Acc-U-Dial device, affords a rapid, convenient, and sensitive method for quantitative determination of a broad range (0.3-1280 micrograms/ml) of urinary albumin levels in the office setting. PMID- 2209305 TI - Lack of effect of clonidine and pentoxifylline in short-term therapy of diabetic peripheral neuropathy. AB - The goal of this study was to confirm or rule out anecdotal reports of beneficial effects of clonidine and pentoxifylline in the treatment of painful diabetic peripheral neuropathy. Clonidine was administered to 16 subjects at two dosage levels (0.1 and 0.2 mg/day) and was compared to placebo in a crossover design, with each phase lasting 4 wk. Either pentoxifylline (400 mg 3 times/day) or placebo was given to 21 subjects in a 12-wk trial. Discomfort was characterized and rated with a subjective pain score (range 0-20). There was a significant decrease in pain score from baseline with both active drugs (P less than 0.05), but this was no better than the response to placebo (P less than 0.30 for clonidine and P less than 0.95 for pentoxifylline). This study does not demonstrate a short-term benefit of either clonidine or pentoxifylline in the treatment of peripheral neuropathy. PMID- 2209306 TI - Measuring vibration sensations with graduated tuning fork. Simple and reliable means to detect diabetic patients at risk of neuropathic foot ulceration. AB - To find a simple and reliable means to measure vibration sensations, 189 diabetic patients and 88 control subjects were tested at different sites with a graduated tuning fork. Within-test variation at big toes reached 8.4% in diabetic patients vs. 2.2% in control subjects. Mean contralateral variation was 7.5% in diabetic patients vs. 2.5% in control subjects. Tuning-fork sensations were inversely correlated with duration of diabetes, whereas no correlation was found with HBA1c levels or the severity of retinopathy. Ninety-nine (52%) patients had vibratory sensation at big toes of less than 99th percentile of normal values for age. In addition, 51% of the patients with clinical symptoms at extremities (n = 67), 70% of the patients without tendon reflexes (n = 50), and 75% of the patients with abnormal nerve conduction velocities (n = 60) also had low vibration sensations. All patients with lower-limb injuries (n = 7) had values at big toes of less than 2. Altogether, the graduated tuning fork represents a simple and reliable alternative to quantitate vibration sensations. Long-term follow-up of asymptomatic patients will indicate whether these abnormalities reflect underlying neuropathy. Patients with abnormal values at screening will necessitate additional investigations and special foot-care education programs. PMID- 2209307 TI - Controlled study in diabetic children comparing insulin-dosage adjustment by manual and computer algorithms. AB - A controlled trial of a new microprocessor device for insulin-dosage adjustment was undertaken in two matched groups of a priori well-controlled diabetic children. A prospective study design with three equal 8-wk periods was used. In the first period, both groups used manual methods for insulin-dosage adjustment after manual criteria. In the second period, one group of children adjusted insulin dosage by computer algorithms, whereas the other continued to use manual methods. In the third period, both groups again adjusted insulin by traditional methods. Mean premeal glycemia and glycosylated hemoglobin levels did not change in either group throughout the study. During the second period, episodes of hypoglycemia were more frequent in children without the computer than in those who used the device. In keeping with the latter outcome, the group that used the microprocessor device was given less insulin in the second period than the first (0.88 +/- 0.02 vs. 0.94 +/- 0.02 U.kg-1.day-1, P less than 0.0001) and in comparison to the control group of patients who concurrently were given an increased insulin dose in the second period compared with the first. This study showed that insulin treatment through specific computer-mediated dosage-adjusting algorithms was safe and minimized hypoglycemia by effectively accommodating seasonally changing insulin requirements. We recommend the device to help diabetic children and their families in the care of insulin-dependent diabetes. PMID- 2209308 TI - Too uptight about tight control? PMID- 2209309 TI - Cheating with glucose test strips. PMID- 2209310 TI - Acquired foot deformity in diabetic children. PMID- 2209311 TI - Pancreatic diabetes with severe generalized allergy to purified beef, pork, and human insulins. PMID- 2209312 TI - Quantitation of the glucose area response to a meal. PMID- 2209313 TI - Sex differences in metabolic control. PMID- 2209314 TI - Hypoglycemia. Can the school respond? PMID- 2209315 TI - Effects of fish oil supplements in NIDDM subjects. Controlled study. AB - The aim of this study was to evaluate the effects of a fish oil preparation (MaxEPA) on hemostatic function and fasting lipid and glucose levels in non insulin-dependent diabetic (NIDDM) subjects. Eighty NIDDM outpatients aged 55.9 yr (mean SD 11.5 yr) participated in a prospective double-blind placebo controlled study of MaxEPA capsules (10 g/day) or olive oil (control) treatment over 6 wk. Patients received either MaxEPA or olive oil in addition to preexisting therapy. Metabolic and hemostatic variables were measured before treatment and after 3 and 6 wk. Platelet membrane eicosapentaenoic acid (EPA) content increased in the treatment group (P less than 0.001). MaxEPA supplementation was associated with a significant fall in total triglycerides (P less than 0.001) but did not affect total cholesterol (P = 0.7) compared with control treatment. Fasting plasma glucose increased after 3 wk (P = 0.01) but not after 6 wk (P = 0.17) treatment with MaxEPA. Spontaneous platelet aggregation in whole blood fell in the MaxEPA group (P less than 0.02) after 6 wk, but there were no changes in agonist-induced platelet aggregation, thromboxane generation in platelet-rich plasma, or plasma beta-thromboglobulin and platelet factor IV levels. An increase in clotting factor VII (P = 0.02), without changes in fibrinogen or factor X levels, occurred in the MaxEPA group. Similar reductions in blood pressure were observed in both groups. Dietary supplementation with MaxEPA capsules (10 g/day) in NIDDM subjects is associated with improvement in hypertriglyceridemia but with deleterious effects in factor VII and blood glucose levels. Most indices of platelet function are unaffected by this therapy. PMID- 2209316 TI - Diabetes, hyperinsulinemia, and hyperlipidemia in small aboriginal community in northern Australia. AB - A small rural Aboriginal community in northern Australia was surveyed for diabetes, impaired glucose tolerance (IGT), hyperinsulinemia, and lipid levels. Of the 122 adults greater than 17 yr of age who participated (95% response rate), 11.5% had diabetes, 7.4% had IGT, and the remaining 81.1% had normal glucose tolerance. Both diabetes and IGT were strongly age related. This high frequency of diabetes occurred, despite the population being relatively lean. Although the body mass index (BMI) increased with age in both men and women, only 25% of the population overall had BMI greater than 25 kg/m2. There were wide ranges of insulin responses to glucose, with the upper tertile of 2-h insulin levels being more than seven times higher than the lower tertile (144 +/- 13 vs. 19 +/- 1 mU/L). Hyperinsulinemia was associated with IGT, elevated triglycerides, and lower high-density lipoprotein cholesterol levels. Lipid abnormalities were much more frequent among men than women. Cholesterol levels were an average of 0.55 mM higher and triglycerides an average of 1.05 mM higher in men than in women, and both increased with age. In conclusion, this small isolated Aboriginal population from northern Australia had an unexpectedly high frequency of diabetes (in view of their relative leanness) in association with a high frequency of metabolic abnormalities indicative of insulin resistance (hyperinsulinemia, IGT, hypertriglyceridemia). PMID- 2209317 TI - Periodontal disease and NIDDM in Pima Indians. AB - The goal of this study was to determine the prevalence and incidence of periodontal disease and its relationship with non-insulin-dependent diabetes mellitus (NIDDM). Two thousand two hundred seventy-three Pima Indians (949 men, 1324 women) aged greater than or equal to 15 yr from the Gila River Indian Community in Arizona were examined between 1983 and 1989. Periodontal disease was diagnosed by tooth loss and by percentage of interproximal crestal alveolar bone loss ascertained from panoramic radiography. Subjects with little or no evidence of periodontal disease were classified as nondiseased. Thus, the incidence of advanced periodontal disease was determined. The age- and sex-adjusted prevalence of periodontal disease at first dental examination was 60% in subjects with NIDDM and 36% in those without. Twenty-two new cases developed in a subset of 701 subjects (272 men, 429 women) aged 15-54 yr who initially had little or no evidence of periodontal disease and had at least one additional dental examination. The incidence of periodontal disease in this group was similar in men and women (incidence-rate ratio 1.0, 95% confidence interval [Cl] 0.5-1.9, controlled for age and diabetes). Higher age predicted a greater incidence of periodontal disease (chi 2 = 30.6, df = 3, P less than 0.001, controlled for sex and diabetes). The rate of periodontal disease in subjects with diabetes was 2.6 times (95% Cl 1.0-6.6, controlled for age and sex) that observed in those without. Although periodontal disease was common in nondiabetic Pima Indians, in whom most of the incident cases occurred, diabetes clearly conferred a substantially increased risk. Thus, periodontal disease should be considered a nonspecific complication of NIDDM. PMID- 2209318 TI - Impact of intensive educational approach to dietary change in NIDDM. AB - The aim of this study was to compare the effects of an intensive educational approach incorporating longer time, greater simplicity, repetition, and cognitive motivational techniques with a conventional one in subjects with established non insulin-dependent diabetes mellitus (NIDDM) whose weight, glycemic control, and diet were not optimal. Subjects were randomly allocated to intensive or conventional education. Of 350 subjects, 70 met the study criteria, which included established NIDDM (greater than or equal to 3 mo), suboptimal recent glycemic control, dietary fat intake greater than or equal to 35% of total energy intake, and body mass index greater than or equal to 25 kg/m2. The intensive approach was associated with significantly greater improvements in dietary compliance, dietary intake (complex carbohydrate, [P = 0.013], legumes [P less than 0.0001], fiber [P less than 0.0001], total fat [P less than 0.004], saturated fat [P less than 0.004]), and total cholesterol level (P = 0.007). The transient improvement in glycemic control was similar in both groups. An intensive education program can improve dietary compliance in established NIDDM subjects more than a conventional one. These recommended dietary improvements achieve better improvement in total cholesterol but do not necessarily improve glycemic control. PMID- 2209319 TI - Effects of childbearing on glucose tolerance and NIDDM prevalence. AB - The goal of this study was to estimate the effects of childbearing on subsequent glucose tolerance and non-insulin-dependent diabetes mellitus (NIDDM) prevalence. A sample of subjects from 64 different locations in the United States were recruited for inclusion in the Second National Health and Nutrition Examination Survey. A complex survey design was used to select a probability sample of subjects from each location. A total of 4577 women were recruited, of whom 3057 underwent clinical and laboratory evaluation for the presence of diabetes mellitus. Women were classified as to their glucose tolerance based on the results of an oral glucose tolerance test or previous physician diagnosis of diabetes mellitus combined with current use of hypoglycemic medication. Childbearing was defined as number of live births experienced by each woman at the time of the interview. Fasting plasma glucose increased linearly with increasing number of live births (coefficient 0.009, 95% confidence interval [CI] 0.006-0.012), as did the 2-h value (coefficient 0.015, 95% CI 0.009-0.021). Adjustment for age, body mass index (BMI), education, and income substantially reduced the magnitude of the association between childbearing and either plasma glucose measurement. When the prevalence of NIDDM in relation to childbearing was examined with logistic regression analysis, a significant linear increase in diabetes prevalence was seen with increasing number of live births (relative prevalence of NIDDM, 1 birth vs. 0 = 1.73, 95% CI 1.39-2.15), but adjustment for age, BMI, education, and income greatly reduced the magnitude of this association (relative prevalence of NIDDM, 1 birth vs. 0 = 1.07, 95% CI 0.98-1.17).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2209320 TI - Lowering of plasma glucose concentrations with bezafibrate in patients with moderately controlled NIDDM. AB - The goal of this study was to investigate whether treatment with bezafibrate improves glucose tolerance in non-insulin-dependent diabetes mellitus (NIDDM). The study included 37 NIDDM patients with HbA1 concentrations greater than 8.5% and normal kidney and liver function who were being treated with diet alone or diet together with a sulfonylurea drug. One patient withdrew because of constipation. At randomization and after 3 mo of treatment, patients were given a standard mixed-test-meal tolerance test (MTT; 500 cal) after an overnight fast, and plasma glucose, insulin, C-peptide, metabolite, nonesterified fatty acid (NEFA), and triglyceride concentrations were measured at 15- to 30-min intervals. Serum lipid, HbA1, and fructosamine concentrations were measured at monthly intervals. Glucose, NEFA, and triglyceride concentrations were significantly lower throughout the second MTT in bezafibrate patients (P less than 0.01-0.001) but not in the placebo group. Fasting serum insulin and C-peptide levels, but not postprandial concentrations, were reduced only in bezafibrate patients (P less than 0.05). After 3 mo, mean fasting serum triglyceride concentrations fell from 2.2 to 1.4 mM (P less than 0.001), total serum cholesterol concentrations from 6.3 to 5.5 mM (P less than 0.001), and low-density lipoprotein cholesterol concentrations from 4.2 to 3.5 mM (P less than 0.001) in bezafibrate patients. There were no changes in serum lipid concentrations in the placebo group. Treatment of patients with moderately controlled NIDDM with bezafibrate improves glucose tolerance and the serum lipid profile. Bezafibrate treatment may be a useful adjunct to hypoglycemic therapy in patients with NIDDM. PMID- 2209321 TI - Comparison of albumin excretion rate obtained with different times of collection. AB - This study was undertaken to assess the usefulness of different techniques for determination of albumin excretion rate (AER). Ninety patients with type I (insulin-dependent) diabetes mellitus and 45 with type II (non-insulin-dependent) diabetes mellitus, with AER/24 h of less than 200 micrograms/min, were included. All patients were free of major systemic complications of diabetes and overt kidney disease (mean serum creatinine 1.1 +/- 0.1 mg/dl, range 0.4-1.2 mg/dl). We compared timed day, night, and 24-h specimens, as well as timed spot specimens during water-induced diuresis. Most patients with type I (75 of 90) and type II (30 of 45) diabetes had AER less than 20 micrograms/min and showed significant differences in AER that were dependent on the collection time. Differences were diminished or absent with AER less than 20 micrograms/min. Sensitivity, specificity, and prediction rates of AER in different specimens were evaluated against 24-h AER. Use of albumin concentrations and albumin-creatinine ratios did not improve test performance in comparison with AER. Sampling time and the overall rate of AER influenced measurement of urinary albumin excretion. Day or 24-h AER is most useful to determine the presence of abnormal AER. AER and albumin concentration in spot samples are of limited use for initial screening and frequently require day or 24-h specimens of AER for confirmation. Day or 24-h AER should be used for long-term follow-up of the diabetic patient. PMID- 2209323 TI - Influenza infection and diabetes mellitus. Case for annual vaccination. AB - Herein, epidemiological data on influenza pneumonia and mortality, results of clinical studies, and the outcome of influenza vaccination trials are reviewed. All excess mortality studies that specify for underlying disease list diabetes as one of the major risk factors. During influenza epidemics, death rates among patients with diabetes mellitus may increase by 5-15%. Diabetes mellitus is also mentioned as a risk factor in most clinical studies, making up 3-14% of the patients studied. Even in recent studies, diabetes mellitus is only preceded as a risk factor by cardiovascular disease and chronic pulmonary disorders. To what extent cardiovascular disease and old age contribute to the increased influenza mortality and morbidity in diabetic patients remains unclear. The influence of epidemic influenza on the incidence of diabetic acidosis in combination with an impaired immune response to both Staphylococcus aureus and the influenza virus suggests that diabetes mellitus itself is the main risk factor. It is concluded that all patients with diabetes mellitus should receive annual vaccinations and that, in official recommendations, patients with diabetes mellitus should be mentioned as a separate risk group. Whole-virus vaccines are preferred over subunit vaccines. PMID- 2209322 TI - Total serum glycosylated proteins in detection and monitoring of gestational diabetes. AB - The goal of this study was to determine whether serum glycosylated protein levels (i.e., fructosamine) can reliably screen for gestational diabetes and whether these levels are valid markers of short-term glycemic control in the third trimester of pregnancy. Ninety-seven pregnant women at 26-28 wk gestation were evaluated over 9 mo. HbA1c and serum glycosylated protein (serum fructosamine) were determined at the baseline venipuncture of the 100-g oral glucose tolerance test performed to detect gestational diabetes. Of the 97 women studied, 13 tested positive for gestational diabetes (National Diabetes Data Group criteria). There were significant differences in the fasting and 1-, 2-, and 3-h glucose values between nondiabetic and diabetic patients (P less than 0.005 at each time point). No difference was noted in the baseline serum glycosylated protein level (2.02 +/ 0.08 vs. 1.98 +/- 0.02 mM, NS) or HbA1c level (4.42 +/- 0.2 vs. 4.6 +/- 0.3%, NS) between gestational and nondiabetic patients. Diabetic patients were followed at 2-wk intervals, with serum glycosylated protein analysis, HbA1c, fasting glucose, and mean glucose determined by outpatient monitoring. Serum glycosylated protein correlated significantly to fasting blood glucose (r = 0.81, P less than 0.001) and mean outpatient glucose (r = 0.62, P less than 0.001) at the 2-wk follow-up visits. No correlation was found between HbA1c and fasting blood glucose (r = 0.11, NS) or mean outpatient glucose (r = -0.12, NS) during the follow-up period. The serum glycosylated protein level (serum fructosamine) is not a useful screening test for gestational diabetes. However, this assay shows potential as an objective marker of short-term control in evaluating the maternal glycemic state. PMID- 2209324 TI - Development of IDDM after donating kidney to diabetic sibling. AB - The goal of this study was to describe a patient who developed insulin-dependent diabetes mellitus (IDDM) after donating a kidney to his sibling and to suggest a possible solution to prevent such an occurrence. A 42-yr-old man was found to have islet cell autoantibodies (ICAs) as part of a screening program of first degree relatives with IDDM. Two years previously, he had donated his kidney to his HLA-identical sibling with long-standing IDDM. Both oral and intravenous glucose tolerance tests demonstrated a gradual loss of insulin secretion and increasing glucose intolerance until the patient developed IDDM 6 yr after the nephrectomy. Whether the presence of ICA is an absolute contraindication to being a kidney donor could be debated. Nonetheless, ICA should be used as a screening test to identify individuals at risk for subsequent IDDM. For those found to be positive, counseling should be provided. PMID- 2209325 TI - Mail-in paper strip vs. microcolumn technique for measurement of glycosylated hemoglobin. AB - We compared glycosylated hemoglobin (GHb) determined from capillary blood samples on paper strips with a standard microcolumn technique in a cross-sectional observational study with laboratories blinded to duplicate samples. Both the standard and the filter strip laboratories were provided with 80 uniquely identified blood samples from 40 individuals. Each laboratory ran duplicate analyses on each sample, yielding 160 GHb values. The within-laboratory correlations between blinded duplicates were 0.98 for the standard (microcolumn technique) and 0.94 for the filter paper (affinity technique) laboratories. The between-laboratory correlations ranged from 0.69 to 0.77. When classifying patients by quartile of glycemic control, the laboratories agreed on 60% of the patients. In an effort to identify sources of between-laboratory variability, varying quantities of blood were applied to strips and reanalyzed. Five microliter drops always yielded inflated estimates of GHb. These data suggest that the estimates of GHb obtained from mail-in paper strips, although internally consistent, differ in important ways from standard laboratory values, reemphasizing the need for caution in the interpretation of interlaboratory and intermethod comparisons. PMID- 2209326 TI - Effect of isocaloric substitution of chocolate cake for potato in type I diabetic patients. AB - Traditional dietary advice given to people with diabetes includes eliminating simple sugars (primarily sucrose) from the diet. Many people have difficulty following this recommendation. Because patients with type I (insulin-dependent) diabetes do not need overall calorie restriction, there is no caloric reason to restrict sucrose. In this study, we looked at the effect of the isocaloric substitution of a piece of chocolate cake for a baked potato in a mixed meal to determine whether this would increase the blood glucose in patients with type I diabetes. The glucose response to a cake-added meal was significantly greater than to a standard meal. The glucose response was no different between a cake substitution meal and a standard meal. The reproducibility studies showed no difference between repeated standard meals. The urinary glucose excretion was significantly greater after a cake-added meal but was no different with the other pairs. There were no significant differences in the counterregulatory hormone responses at baseline between any of the paired studies. In conclusion, patients with type I diabetes may substitute a sucrose-containing dessert for another carbohydrate in their diet without compromising their postprandial glucose response. These data suggest that a dessert exchange may be helpful and not harmful in the management of diabetic patients. There is an inherent variability (at least 16%) in an insulin-requiring patient's response to a meal, making self monitoring of blood glucose and adjustment of insulin doses necessary to achieve near euglycemia. PMID- 2209327 TI - Relationship of psychiatric illness to impotence in men with diabetes. AB - Clinical data from 37 adult males with diabetes mellitus (insulin dependent, n = 22; non-insulin dependent, n = 15) who had undergone psychiatric diagnosis and peripheral nerve conduction studies were reviewed to determine whether psychiatric illness was significantly related to complaints of sexual dysfunction. Main-effects testing revealed that impotence was associated with both neuropathy (P less than 0.01) and psychiatric illness (P less than 0.001). Logistic regression analysis was then used to determine the independent relationships of these two variables with impotence. After controlling for the effects of neuropathy, psychiatric illness (generalized anxiety disorder and depression) remained significantly associated with sexual dysfunction (P less than 0.01). These data allow for the hypothesis that psychiatric illness may be an important contributor to impotence in diabetic men, as it is in nondiabetic men, even when neuropathic complications of the disease are present. PMID- 2209328 TI - Oral contraceptives in women with diabetes. AB - We evaluated the association of oral contraceptive use with the presence and severity of diabetic retinopathy, hypertension, and glycosylated hemoglobin in women of childbearing age who have diabetes. Neither current or past use nor number of years of use of oral contraceptives was associated with severity of retinopathy, hypertension, or current glycosylated hemoglobin. In conclusion, further study of various birth control methods in young women of childbearing age should be considered. PMID- 2209330 TI - Emotional side effects of diabetes educational program. PMID- 2209329 TI - Comparison of HbA1 and fructosamine in diagnosis of glucose-tolerance abnormalities. AB - Total glycosylated hemoglobin (HbA1) and fructosamine were evaluated as screening tools for detection of glucose-tolerance abnormalities in 144 asymptomatic subjects undergoing a 75-g oral glucose tolerance test. Subjects were classified according to World Health Organization criteria as having normal (n = 78), impaired (n = 40), or diabetic (n = 26) glucose tolerance. We found good specificity for HbA1 and fructosamine (100 and 97%, respectively) but low sensitivity (15 and 19%, respectively). At the intersection of the curves of sensitivity and specificity drawn from various thresholds of normality, both sensitivity and specificity were 75% for HbA1 and 55% for fructosamine. Thus, neither HbA1 nor fructosamine seems to be suitable for the diagnosis of mild abnormalities in glucose tolerance. PMID- 2209332 TI - Change in army policy. PMID- 2209331 TI - Pediatric primary care for children with IDDM. PMID- 2209333 TI - Relationship of maternal and fetal outcome to glucose tolerance during pregnancy in whites and Indian Asians. PMID- 2209335 TI - Blastocystis hominis treatable cause of diabetic diarrhea. PMID- 2209334 TI - Hemolytic anemia associated with sulfonylurea use. Case study and review of literature. PMID- 2209336 TI - Effect of tea prepared from leaves of Syzygium jambos on glucose tolerance in nondiabetic subjects. PMID- 2209338 TI - Sulfonylurea drugs: basic and clinical considerations. A symposium presented before the 13th International Diabetes Federation Congress. Sydney, Australia, 20 November 1988. Proceedings. PMID- 2209337 TI - Diabetic eye disease detection by primary-care physicians. PMID- 2209339 TI - Sulfonylureas. Why, which, and how? AB - Although controversies remain as to the usefulness of sulfonylureas, most evidence is in favor of their use in many if not patients with non-insulin dependent diabetes mellitus. When used properly, sulfonylureas improve insulin secretion and action, and these effects may be maintained for years. If combined with hypocaloric dietary regulation, rapid- and short-acting sulfonylureas may help patients reach and maintain euglycemia without provoking chronic hyperinsulinemia or weight increase. There is no evidence that sulfonylurea treatment causes beta-cell exhaustion; instead, the antihyperglycemic effect helps improve beta-cell function. Sulfonylurea "failures" are often dietary failures or may be due to late introduction of these drugs, i.e., when beta-cell function is already attenuated. Desensitization of the insulinotropic effect of sulfonylureas may occur but might be avoided by discontinuous (less than 24 h/day) sulfonylurea exposure, i.e., once-daily administration of a short-acting sulfonylurea in a moderate dose. The most important adverse effect of sulfonylureas is long-lasting hypoglycemia, which may lead to permanent neurological damage and even death. This is mainly seen in elderly subjects who are exposed to some intercurrent event, e.g., acute energy deprivation or a drug interaction, i.e., aspirin. Long-acting sulfonylureas may be more likely to promote long-lasting hypoglycemia. The dose-response relationships of sulfonylureas have been poorly investigated, and sulfonylurea therapy should always be initiated and maintained at the lowest possible dose. PMID- 2209341 TI - Effect of acarbose on carbohydrate and lipid metabolism in NIDDM patients poorly controlled by sulfonylureas. AB - The ability of acarbose to lower plasma glucose concentration was studied in 12 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were poorly controlled by diet plus sulfonylurea drugs. Patients were studied before and 3 mo after the addition of acarbose to their treatment program, and a significant improvement in glycemic control was noted. Although the decrease in fasting plasma glucose concentration was modest (12.0 +/- 0.8 to 10.8 +/- 0.3 mM), average postprandial plasma glucose concentration decreased by 3.4 mM. When acarbose therapy was discontinued in 5 patients, plasma glucose levels rapidly returned toward pretreatment levels. In addition to the improvement in glycemia, acarbose treatment also led to a significant reduction in HbA1c (7.4 +/- 0.2 to 6.4 +/- 0.2%, P less than 0.01) and triglyceride (2.4 +/- 0.1 to 2.1 +/- 0.1 mM, P less than 0.01) concentrations. Neither the plasma insulin response to meals nor insulin-stimulated glucose uptake improved with acarbose therapy, consistent with the view that acarbose improves glycemic control by delaying glucose absorption. Considerable individual variation was noted in the response to acarbose, and the results in 4 patients were dramatic, with striking reductions in both fasting and postprandial glucose concentrations. The addition of acarbose to patients with NIDDM not well controlled by sulfonylureas appears to have significant clinical benefit. PMID- 2209340 TI - Characterization and significance of sulfonylurea receptors. AB - This study describes and characterizes a putative sulfonylurea receptor. The radioligand used was [3H]glipizide (9 Ci/mmol). The beta-cell plasma membranes were derived from a transplantable rat insulinoma generated by subcutaneous injection of RINm5F cells and purified by ultracentrifugation on a 15-55% sucrose gradient. Specific binding of [3H]glipizide to purified beta-cell plasma membranes was determined to be maximal at temperatures of 4-23 degrees C, pH 7.3, and an incubation of 2 h. Scatchard analysis indicated a single binding site with Kd = 7 nM and sulfonylurea binding of 0.93 pmol/mg membrane protein. Displacement of [3H]glipizide from the purified beta-cell plasma membranes by various sulfonylureas and their analogues correlated well with their known hypoglycemic and insulin-releasing activities. Various agents, including nutrients, agents affecting Ca2+ flux, gastrointestinal hormones, and pancreatic hormones, had no effect on [3H]glipizide binding to the beta-cell plasma membranes. Putative sulfonylurea receptors on beta-cell and brain cell plasma membranes have been reported by several groups of investigators. Sulfonylurea binding to the beta cell is hypothesized to close an ATP-sensitive K+ channel, which leads to depolarization of the membrane and activation of a voltage-dependent Ca2+ channel. PMID- 2209342 TI - Biguanides and sulfonylureas as combination therapy in NIDDM. AB - Oral combination therapy with biguanides (metformin) and sulfonylureas is discussed. The rationale for the use of this combination is based on the different sites of action of the two kinds of drugs and the possibility for obtaining additive or potentiating effects and reduced side effects. The clinical usefulness of chlorpropamide and glyburide in combination with metformin has been demonstrated in some clinical trials. The combination may provide satisfactory glycemic control for several years, and possibly insulin therapy can be postponed or even avoided. No special safety problems are encountered with the use of the combination other than those attributed to the use of metformin or sulfonylurea alone, i.e., lactic acidosis and hypoglycemia, respectively. The lethality risks of these associated conditions are comparable. It is concluded that more data are needed to evaluate the full clinical potential and the mechanism of action of oral combination therapy. PMID- 2209344 TI - Combined insulin-sulfonylurea therapy in treatment of NIDDM. AB - For the past few years, interest has focused on the combination of insulin and sulfonylurea in the search for effective treatments for non-insulin-dependent diabetes mellitus (NIDDM) patients who fail on oral hypoglycemic agents. Although several studies have demonstrated beneficial effects of such therapy in NIDDM patients, the average effect is small and is observed in only about half of the patients. However, there are several problems with most previous studies, including small sample size, selection of patients, and simultaneous use of several end points. First, residual beta-cell function has been considered to be a prerequisite for a beneficial effect of combination therapy. Therefore, most studies have failed to demonstrate improved glycemic control after adding sulfonylurea to insulin therapy in patients with insulin-dependent diabetes mellitus. Inclusion of patients with impaired beta-cell function will therefore attenuate the effect of combination therapy. Second, most studies have used glycemic control as an end point. Nevertheless, the insulin dose has been reduced by 20-30% to avoid hypoglycemia after adding sulfonylurea to insulin. Thus, the comparison has been made between treatments with a smaller insulin dose with sulfonylurea and a larger insulin dose without sulfonylurea. The patient most likely to benefit from combination therapy is slightly obese, has had NIDDM for a relatively short period, and has preserved beta-cell function. In such a patient, combined insulin-sulfonylurea therapy predominantly stimulates basal insulin secretion, resulting in more effective suppression of hepatic glucose production and lower fasting plasma glucose. The side effects are few, most notably more frequent but mild hypoglycemic reactions. PMID- 2209343 TI - Metabolic effects of combination glipizide and human proinsulin treatment in NIDDM. AB - The effects of 3 mo of treatment with a combination of glipizide and human proinsulin were studied in a small group of closely monitored patients. The patients had non-insulin-dependent diabetes mellitus (NIDDM) and poor glucose regulation, despite maximal sulfonylurea therapy. This was a randomized double blind placebo-controlled trial in which there were three treatment groups who received either 20 mg glipizide given 30 min before breakfast and dinner and human proinsulin given subcutaneously at bedtime (n = 5), glipizide and human proinsulin placebo (n = 5), or glipizide placebo and human proinsulin (n = 5). Glycemic regulation was assessed by measurements of 24-h plasma glucose profiles and glycosylated hemoglobin. Our observations demonstrate that the combination of glipizide plus human proinsulin was more effective than either agent alone in controlling overall glycemia in patients with NIDDM. The data support the concept of use of an agent during the day that has its major effects postprandially and another agent at bedtime that is relatively hepatospecific. PMID- 2209345 TI - Will sulfonylurea treatment of impaired glucose tolerance delay development and complications of NIDDM? AB - The chronic hyperglycemia of non-insulin-dependent diabetes mellitus (NIDDM) evolves gradually and is usually preceded by more transient hyperglycemia, classified as impaired glucose tolerance (IGT). Already in this phase, there is an increased risk of cardiovascular complications, and many IGT subjects, like NIDDM patients, often display several of the metabolic and circulatory disturbances that are associated with hyperglycemia, e.g., insulin resistance, hyperinsulinemia and/or hyperproinsulinemia, delayed insulin release, dyslipidemia, and hypertension. Therefore, and because untreated hyperglycemia is a self-perpetuating condition, early detection and early intervention may be necessary to prevent the progression and complications of NIDDM. This in turn would necessitate screening procedures, and the therapeutic goal should include both euglycemia and normalization of plasma insulin, plasma lipids, and blood pressure. A study in the German Democratic Republic indicated that the mortality in screening-detected NIDDM patients did not differ from that in patients detected in routine care. In a Swedish study on screening-detected NIDDM subjects, only those who had IGT rather than manifest NIDDM could maintain fasting blood glucose less than or equal to 6 mM for 5 yr by hypocaloric dietary regulation alone. In those with screening-detected NIDDM, the delayed acute insulin release and net postprandial hyperglycemia were improved by addition of glipizide, and most managed to attain and maintain fasting blood glucose less than or equal to 6 mM for approximately 2 yr after such addition. However, after 4 yr, there was an increase in blood glucose, suggesting that preventive intervention either may not be possible or may have to start in the IGT phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2209346 TI - Mechanisms of sulfonylurea-induced insulin release. AB - The mechanisms responsible for the stimulation of insulin release from the pancreatic beta-cell by hypoglycemic sulfonylureas are reviewed herein. One hypothesis postulates that these agents act, at the level of the plasma membrane, by causing the closure of a class of K+ channels characterized by their sensitivity to ATP. This may lead to depolarization of the plasma membrane, gating of voltage-sensitive Ca2+ channels, increase in cytosolic Ca2+ activity, and activation of the effector system for insulin release. However, it is not evident that the closure of ATP-sensitive K+ channels accounts for effects of sulfonylureas such as inhibition of K+ inflow into the islet cells, increase in their Na+ content, or even stimulation of Ca2+ inflow and insulin release at physiological or higher concentrations of D-glucose. PMID- 2209347 TI - Identification of Campylobacter pylori by endoscopic brush cytology. AB - To investigate the value of Papanicolaou-stained endoscopic brush samples in the diagnosis of Campylobacter pylori infection of the upper gastrointestinal tract, 138 brush and biopsy samples from the esophagus, stomach, and duodenum, taken concomitantly, were reviewed retrospectively. In 35 cases, Campylobacter-like organisms (CLOs) were found in both cytology and biopsy samples. In 15 cases, CLOs were seen in biopsy material only, and in 8 cases, CLOs were found in cytology material only. CLOs were found in 49% of the gastric specimens and 33% of the Barrett's esophagus specimens by histologic or cytologic examination or by both methods. CLOs were found by at least one method in 64% of the gastric samples with active gastritis 40% with borderline gastritis, 15% without gastritis, and in 64% with adenocarcinoma. Cytologic examination of endoscopic brush samples is a valuable technique for the diagnosis of gastric Campylobacter infections and can be performed easily in cytopathology laboratories. PMID- 2209348 TI - Radiation changes in endocervical cells in brush specimens. AB - Although the cytologic changes in cervical and vaginal squamous cells after radiation therapy were well-described decades ago, alterations in endocervical cells in response to radiation therapy have not been delineated in detail. We studied the effect of radiation therapy (usually combined linear accelerator beam and radium insertion) on endocervical cells as seen in endocervical brush specimens from 24 patients treated for cervical cancer. Of the 40 smears examined, 45% were taken 3-6 mo after the completion of radiotherapy, 28% at 10 14 mo, and 20% at 18-34 mo. Endocervical cells appeared as single cells and in clusters and had lavender, mucin-filled cytoplasm. When present in clusters, they lacked the honeycomb appearance of normal endocervical cells. In smears taken at 3-6 mo, the majority of endocervical cells were enlarged (100% of smears) but they usually had normal nuclear/cytoplasmic ratios. Their nuclei were enlarged (100% of smears); varied in size (100%); had some coarse chromatin (67%) and large nucleoli (78%); and were multinucleated (89%). Repair cells and multinucleated histiocytes were seen in 83% and 61% of smears, respectively. Each of these cytologic findings was less apparent in follow-up smears taken more than 6 mo after the completion of radiation therapy. Awareness of these cytologic changes in endocervical cells after radiation therapy precludes the overdiagnosis of cancer in follow-up endocervical brush specimens. PMID- 2209349 TI - Diagnosis of squamous-cell carcinoma of the lung by sputum cytology: with special reference to correlation of diagnostic accuracy with size and proximal extent of resected tumor. AB - Sputum cytology was performed in 179 cases of squamous-cell carcinoma of the lung; 134 cases were diagnosed as positive. There were no significant differences in diagnostic accuracy of sputum cytology between tumors sizes. In cases with tumors extending proximally into the main, lobar, or segmental bronchi, the diagnostic accuracy of sputum cytology was significantly higher than in cases where the proximal invasion of tumor was limited to the peripheral bronchi. In cases with tumors 3 cm or less in diameter, when tumors extended proximally into main, lobar, or segmental bronchi, the diagnostic accuracy of sputum cytology was significantly higher than in cases with tumors extending proximally into subsegmental or subsubsegmental bronchi. In peripherally located squamous-cell carcinoma, in cases in which the tumor arose in subsegmental or subsubsegmental bronchi, carcinoma could be detected by sputum cytology even when it was roentgenographically occult. PMID- 2209350 TI - Fine-needle aspiration cytology of hematopoietic lesions from multiple sites. AB - We reviewed 130 fine-needle aspiration (FNA) biopsies from 118 patients with a variety of benign and malignant hematopoietic lesions. There were 74 (57%) malignant, 45 (35%) benign, and 11 (8%) atypical diagnoses. Immunocytochemistry of the aspirated material was performed in 47 (36%) and electron microscopy in 4 (3%) of the cases. FNA cytology was utilized to make a primary hematopoietic malignant diagnosis in approximately half of the cases and to confirm recurrence in the remainder. The malignant cases included non-Hodgkin's lymphoma. Hodgkin's disease, medullary and extramedullary plasmacytoma, and granulocytic sarcoma. Forty-two malignant cases had either previous or follow-up surgical biopsy with no false-positive diagnoses. Of the 11 atypical cases, seven had surgical confirmation with five malignant and two benign diagnoses. The benign hematopoietic lesions correctly identified included acute and chronic lymphadenitis, granulomatous processes, and eosinophilic granuloma. Only 5 of the 45 benign FNA biopsies had surgical pathology follow-up, with no false-negative diagnoses. The most commonly aspirated sites were lymph nodes (71%), although hematopoietic lesions were correctly identified in a number of extranodal locations, including soft tissue (8%), abdominal viscera (6%), lungs (5%), mediastinum (2.5%), bone (3%), and thyroid, salivary gland, and breast (1.5% each). This study demonstrates the clinical utility and diagnostic accuracy of FNA cytology in the evaluation of benign and malignant hematopoietic disorders from multiple sites. Ancillary studies performed on the aspirated material aided in making a specific and accurate diagnosis. PMID- 2209351 TI - Aspiration biopsy of the prostate gland: a brief review of collection, fixation, and pattern recognition with special attention to benign and malignant prostatic epithelium. AB - The preparation and use of an alternate collection device for aspiration biopsy of the prostate is presented. The device is inexpensive and can be constructed from readily available office materials. Its use in conjunction with a liquid phase collection of cellular products of aspiration biopsy by a backwash technique is described. Following this, a brief discussion of pattern recognition in cytological preparations of benign and malignant prostate epithelial aggregates is presented and illustrated. PMID- 2209352 TI - Identification of papillary carcinoma in a thyroglossal cyst by fine-needle aspiration biopsy. AB - Papillary carcinoma was diagnosed in a fine-needle aspirate from a cystic upper cervical midline lesion attached to the hyoid bone. Histological examination of the excised specimen verified the diagnosis. Carcinoma arising in thyroglossal cysts, though rare, should be considered in patients presenting with an anterior midline mass in the upper neck; fine-needle aspiration may be useful in the preoperative diagnosis. PMID- 2209353 TI - Psammoma bodies in fine-needle aspiration cytology of papillary adenocarcinoma of the lung. AB - The fine-needle aspiration (FNA) cytology of two cases of papillary adenocarcinoma of the lung is reported. Both cases showed psammoma bodies and papillary clusters of tumor cells in FNA specimens. Both tumors were resected and confirmed as primary papillary carcinoma of the lung by histologic examination and by clinicopathologic exclusion of the possibility of metastasis from other organs. PMID- 2209354 TI - Fine-needle aspiration cytology of pilomatrixoma: a case report. AB - The cytological appearance of breast lesions has been well-studied. However, skin lesions occurring as breast nodules have less often been studied by fine-needle aspiration. In addition. skin tumors occurring over the breast may be clinically mistaken for breast carcinoma owing to their fixity to the skin. This article presents one such case and describes its cytologic appearance. PMID- 2209355 TI - Infantile myofibromatosis: diagnosis suggested by fine-needle aspiration biopsy. AB - A newborn male infant presented with multiple subcutaneous and parenchymal lesions. These lesions, thought clinically to represent disseminated neuroblastoma, were assessed via fine-needle aspiration biopsy. The spindled cells and associated collagen were interpreted as a type of fibromatosis, most probably infantile myofibromatosis. This diagnosis was subsequently confirmed histologically, and the patient experienced spontaneous involution or regression of all lesions by 18 mo of age. To our knowledge, this is the first documented case of this entity initially suggested on the basis of a fine-needle aspiration biopsy specimen. PMID- 2209356 TI - Managing somatization disorder. AB - Somatization disorder (SD), a chronic psychiatric illness that affects about 1% of adult women, is characterized by multiple somatic complaints. It should be suspected in any woman who presents with a vague or complicated history; unaccountable non-responsiveness to therapy; dramatic, seductive or demanding personality style; family history of personality disorder; sexual abuse as a child; substance abuse; or depression with atypical features. Its cause is unknown, although both genetic and environmental factors have been implicated. At follow-up, patients with SD continue to have somatic symptoms, but many improve with therapy. Nearly two thirds of patients with SD attempt suicide, but few complete it; however, completions may be more common than formerly realized. There is no specific treatment for SD, but management can be organized around the following ABCs: Accommodate initially to forge rapport; Behavior modification (ignore symptoms, praise for improved behavior); Confrontation later about effects of behavior style; Decrease drugs gradually, with praise for reduction; Educate about course and meaning of illness; Family involvement to give information and help with treatment; Guilt should be assuaged in physicians, who may blame themselves when patients do not improve; Hospitalize (closed psychiatric unit) only for serious suicide risk, substance abuse, or other extreme behavior; and Intercurrent depression should be treated conservatively. PMID- 2209357 TI - Myasthenia gravis. AB - Myasthenia Gravis is a disorder of neuromuscular function resulting from an immunologically based premature destruction of acetylcholine receptors. The disease is characterized clinically by variable weakness accentuated by repetitive muscular activity and usually responding to the administration of acetylcholinesterase inhibitors. Myasthenia Gravis is a complex disease and requires understanding of the many facets of its natural history and immunological basis to ensure optimal individual patient management. The long term goal is control of the immunological imbalance; treatment regimens include thymectomy, corticosteroids, azathioprine, and plasmapheresis. The common use of acetylcholinesterase inhibitors provides symptomatic relief during variable daily muscular activity. Disability due to myasthenia gravis is to a large extent reversible and death is preventable. Early recognition of myasthenia gravis and appropriate treatment are often rewarded by remission that may be permanent. PMID- 2209358 TI - History of ophthalmology, 3. PMID- 2209359 TI - Osler and ophthalmology. PMID- 2209360 TI - Ocular manifestations during the French travels of discovery to Australia from Laperouse (1741-1788) to Dumont D'Urville (1790-1842). PMID- 2209361 TI - The blind Belisar as beggar. AB - The blind Belisar as an example of the sudden fall from honour and glory to poverty and distress inspired not only Rembrandt but also several artists from the 17th to the 19th century. The contemporary historians report that Belisar was dismissed by Justinian because of envy and distrust and that he died in poverty. Details about his blinding can be found only in an epic of the 12th century. A report is given about the different gruesome techniques of blinding that existed during the centuries of Byzantine empire. PMID- 2209362 TI - Eye references in the Homeric Epics. AB - After a short introduction to the Homeric Epics, the name of Homer and the time and place where the poems were written, the authors refer to the terms of the eyes and to the verses where they are found. Among these terms, the most important is the term omicron phi theta alpha lambda mu omicron sigma, the first term for the eye in ophthalmology, which has remained throughout the years unchanged. Finally, they refer to the injuries of the eyes, the participation of the two sons of Asclepios in the Trojan campaign and to the verses including the classical paragraph '... a doctor is more capable than the other men ...' Both Epics relating to the cardinal human values: prudence, temperance, fortitude and justice, contain the lofty ideal of human excellence, called by the Greeks alpha rho epsilon tau eta. PMID- 2209363 TI - King Sivi and Doctor Silva. AB - The classical legend of ca. 500 BC about Buddha who in his former life as King Sivi wished to give a part of his body to the first one who asked for it, lies at the root of the success story of the indefatigable Dr Silva of Colombo, who succeeded through the oldest known story about donation of organs to make Sri Lanka the 'world champion' in eye donation. The legend is quoted in this article, followed by a short introduction of Dr Hudson Silva and his remarkable activities. PMID- 2209364 TI - The ophthalmology of Fabricius Hildanus in the 17th century. AB - Wilhelm Fabricius, born in Hilden, near Dusseldorf, (Fabricius Hildanus) lived from 1560 until 1634. He had been working as physician and surgeon in Switzerland. He left a voluminous literature posthumously edited as 'Opera observationum et curationum medicochirurgicarum'. It is a compendium of 600 extremely interesting pathological cases, some of them in form of letters to close colleagues. Ophthalmology is represented by quite a big chapter, one of them reports a successfully performed exenteratio orbitae because of a tumor. Further parts, for example, describe special ophthalmic twizzers with certain fixing mechanisms and some kind of an operation table equipped by an adjustable prop for the operator's arm. Fabricius points out that after perforation of the eye the loss of aqueous humour is not consequently noxious. He, too, demonstrates the treatment of a symblepharon and describes amongst other therapies the first successful magnetic extraction of an iron foreign body out of the eye in ophthalmic history. PMID- 2209365 TI - Ophthalmological ideas of the Byzantine author Meletius. AB - The authors study and analyze the ophthalmological knowledge of the monk Meletius of the Monastery of St. Trinity in Tiveriopoli, as they appear in his paper 'De Natura Hominis'. The ophthalmological knowledge of Meletius mainly concerns the anatomy and physiology of the eye. The authors reach the conclusion that Meletius' ophthalmological knowledge for the greater part is compiled from that of the ancient authors; but they define a great number of pioneering medical ideas of Meletius, of which further research could discover the origin. PMID- 2209366 TI - Ophthalmology according to Aetius Amidenus. AB - The authors analyze the diseases described in the chapter 'Concerning the maladies of the eye' by the outstanding Byzantine author Aetius Amidenus. Where possible, the authors try to compare the medical ideas of Aetius with the up-to date nosologic entities. To give a more comprehensive analysis, the authors try to complete the classification of diseases on an anatomic basis, following in most of the points that of Aetius. The ophthalmological diseases are classified as follows: a) eye-lids; b) cornea; c) sclera and conjunctiva; d) anterior chamber, iris and lens; e) lacrymal ducts; f) disturbances of the vision; and g) various others. The authors emphasize that the seventh chapter (Z' logos) constitutes a significant ophthalmologic manual, containing almost all the pertinent knowledge of that time. PMID- 2209367 TI - Father Waclaw Szuniewicz, M.D., an ophthalmologist of unusual courage and devotion. AB - The authors present a short biography of the missionary-priest ophthalmologist Waclaw Szuniewicz (1892-1963). This remarkable man completed his ophthalmologic training between 1922 and 1927 at the Department of Ophthalmology of the Stefan Batory University in Wilno, Poland. From 1931 to 1949 he served as a missionary priest in China, and for part of this time he was the head of the Department of Ophthalmology at a hospital in the Chinese town of Shuntehfu. He organized and ran a 100 bed ophthalmology department there, also supervising 18 outpatient clinics in the surrounding area. During this period he regularly saw over 145,000 patients and performed over 5000 ophthalmic operations a year! From 1949 to 1952 Dr Szuniewicz carried out research work on the surgical treatment of corneal astigmatism. His interesting refractive procedures were done at Yale University in the USA and the techniques he developed arose from the work he had initially done in China from 1946 to 1948. Dr Suniewicz moved from the USA to Brazil in 1952 where he continued his refractive surgery research until 1954 and his missionary service until his death in 1963. PMID- 2209368 TI - On the history of deformation phosphenes and the idea of internal light generated in the eye for the purpose of vision. AB - Deformation phosphenes are light sensations evoked by deformation of the eyeball in total darkness. They were first reported in Western literature by Alcmaeon of Croton in the fifth century B.C. The phenomenon of deformation phosphenes was instrumental in prompting some pre-Socratic philosophers and Plato to conceive the idea that efferent light is emitted from the eye for the purpose of vision and a 'cone of vision' is formed by interaction with the external light. In the theories of vision this cone of vision played an important role as a signal transmitting structure and was also used by the Greek opticians as a geometrical construction to explain optical properties of vision. The impact of the deformation phosphene experiment on the ideas of visual sensation can be followed from Greek antiquity through the period of Roman dominance and Galen's medical teaching on to medieval times and up to the late Renaissance when, based on the anatomy of the eye as illustrated by Felix Platter, the image formation on the retina was correctly described for the first time by Johannes Kepler. In the generations following, deformation phosphenes were still employed as an important argument in defence of the theories of vision. However, the idea of physical light generated by eyeball deformation was rejected with increasing frequency during the 17th and 18th centuries. The literature on this topic is discussed, comprising the contributions of the Arabic philosophers and physicians of the 9th and 10th centuries A.D., the Franciscan and Dominican philosophers of the 13th century, Nicolaus Cusanus of the 15th century, several anatomists of the 16th and 17th centuries, Kepler, Plempius, Descartes, Boyle, Newton and others. After Kepler, the mechanical interpretation of the deformation phosphene being caused by direct action of the eyeball deformation onto the retina slowly became dominant, and the idea that physical light is generated in the eye disappeared. The experimentum crucis in this matter was performed by Giovanni Battista Morgagni (1682-1771) and repeated and extended by Georg August Langguth (1711 1782). On the basis of their results, the case for physical light being generated in the eye by deformation was refuted definitively and slowly vanished thereafter from scientific literature. Deformation phosphenes were used in the 19th and 20th centuries as an instructive example of the percepts evoked by inadequate stimulation of a sense organ. J.E. Purkyne in particular contributed to the study of deformation phosphenes, and finally in 1978, F. Tyler devoted a careful study to the differences between monocular and binocular deformation phosphenes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2209369 TI - Antonie Cramer's explanation of accommodation. AB - In the middle of the last century the question of the origin of accommodation was still unsolved. At the suggestion of Donders, Cramer used in 1851 a microscope to demonstrate that accommodation has to be ascribed to an increase in the curvature of the lens. Donders himself had several instruments made for the same purpose. These are still present in the collection of the Royal Netherlands Ophthalmic Hospital. PMID- 2209370 TI - Life, eye disease and work of Joseph Plateau. AB - The Belgian physicist Joseph Plateau (1801-1883) suffered from uveitis which made him blind at the age of 42 years and which has been ascribed to a previous solar retinitis. Plateau described many visual phenomena, including the persistence of visual impressions. He invented instruments which foreshadowed the cinema. PMID- 2209371 TI - 19th century mechanical models of eye movements, Donders' law, Listing's law and Helmholtz' direction circles. AB - Donders, Ruete, von Graefe, von Helmholtz, Listing, Volkmann and many others have provided the broad outline of an answer to the question how the eye rotates during eye movements. Many mechanical models of eye movements, ophthalmotropes, have been constructed and studied in the nineteenth century. These models have primarily served to explain Donders' and Listing's Laws on the nature of eye movements. As both Donders' Law and Listing's Law are easier to understand when seen against the background of the coordinate systems used to describe eye movements, all of the coordinate systems currently in use in the diagnosis and treatment of strabismus are described. In addition, the reader is introduced to a coordinate system based on von Helmholtz' direction circles, circles describing the direction of the horizontal and vertical retinal meridians in all positions of gaze. PMID- 2209372 TI - Perinatal ocular physiology and ROP in the experimental animal model. AB - In order to overcome the scarcity of premature human ocular tissues and the enormous obstacles to direct examination of immature human ocular vasculatures, a number of animal models have been employed by investigators in order to study various aspects of ROP. A variety of factors may influence selection of the particular model used, but ultimately it is the faithfulness with which the model mimics human ROP that is most important. The validity of the models has been and remains a controversial subject, but evidence appears strong in favor of the beagle puppy model for studying physiology of the ocular vasculatures during perinatal development. Human ROP pathology usually is defined in terms of static morphological state, physiological dysfunction being considerably more difficult to assess. Most of the animal models fall short of mimicking the pathological lesions found in human eyes, especially those associated with severe, or end stage ROP, yet they do fairly well in terms of mimicking the retinal vascular physiological changes associated with onset of the disease. Unfortunately, where the physiological aspects of ROP are concerned, focus is primarily on the effects of hyperoxia; other physiological factors as well as the potential role of the choroid are essentially ignored. This paper discusses the potential of physiological changes which occur during the perinatal period to play a role in ROP pathogenesis. PMID- 2209373 TI - The mouse model of oxygen-induced retinopathy: a suitable animal model for angiogenesis research. AB - Newborn mice exposed to high (greater than 98%) ambient oxygen during the newborn period and subsequently removed to room air will develop a proliferative retinopathy which mimics the neovascular component of acute retinopathy of prematurity. In this paper, we report preliminary ultrastructural findings on the vitreous new vessels in the mouse model of oxygen-induced retinopathy, and argue that the model is appropriate for research on non surgical treatments for ROP in particular and angiogenesis in general. PMID- 2209374 TI - Oxygen-induced retinopathy in the rat model. AB - Identification of a suitable animal model is essential for the continued study of retinopathy of prematurity (ROP). Since 1984 we have used the newborn rat for the study of oxygen-induced retinopathy (OIR). The rat retina is highly immature at birth. Like those of humans, the retinal vessels arise from mesenchymal precursors, but contrary to that which occurs in humans, canalization of the rats inner retinal vessels is not related to the presence of cystoid spaces. In addition, only immature Stage I photoreceptors are present around the optic disk at birth. This extreme immaturity makes the rat retina highly susceptible to direct damage from oxygen. Oxygen-induced retinopathy can be produced by exposing the newborn rat to 80% oxygen for the first 7-10 days of life. We have demonstrated that OIR does not develop when oxygen is administered under conditions of moderate hyperbarism (+1.8 atm). It is possible that hyperbarism exerts a protective effect on the immature retinal vessels by inducing a vasoconstrictive response which reduces the amount of oxygen transported from the choroid to the inner retina during hypoxia. I recently hypothesized that this vasoconstriction might also affect the ciliary body, thus reducing the quality of aqueous produced, and we are currently studying the relationship between development of the immature retinal vessels in the rat and production and drainage of the aqueous. The question we are attempting to answer is whether a condition of relatively increased intraocular pressure is capable of promoting the development of OIR. PMID- 2209375 TI - Oxygen-induced retinopathy in the rat: possible contribution of peroxidation reactions. AB - Albino rats were maintained in 60% atmospheric oxygen from birth through 14 days of age. Age-matched controls were simultaneously raised in room air. Some rats were perfused with India ink before sacrifice and retinal dissection in order to study the effect of oxygen-rearing on the retinal vasculature. By this method it was found that oxygen-reared animals sustained a 36% loss of retinal blood vessels. Other animals' retinas were removed immediately after sacrifice and examined for evidence of lipid peroxidation by one of three means: 1) a determination of the presence of products of lipid peroxidation, 2) a measure of the loss of polyunsaturated fatty acids, and 3) a determination of retinal vitamin E level. Each of these determinations indicated that peroxidation reactions had occurred in the retinas of oxygen-reared rats. Retinal vitamin E was supplemented in the young rats through the diet of the mothers. This treatment resulted in a two-fold increase of retinal vitamin E over levels in pups of mothers fed rat chow. Oxygen-reared vitamin E-supplemented rats sustained significantly less obliteration of blood vessels than non-supplemented oxygen reared animals. PMID- 2209376 TI - The role of hyperoxia in the aetiology of retinopathy of prematurity. AB - Oxygen in excess is toxic to living tissues and a capacity to neutralise its harmful potential is a requirement for survival. Experimental and circumstantial clinical evidence suggests that the requisite protective mechanisms are insufficiently advanced in the retinal vasculature of the premature neonate, such that babies of very low birth weight are vulnerable to even minor hyperoxia. Sustained hyperoxia produces degenerative effects on the developing endothelium with the result that the newest vessels at the retinal periphery are obliterated. Factors other than the level of inspired oxygen per se may serve to increase the risk of retinopathy by raising the rate of delivery of hyperoxygenated blood. PMID- 2209377 TI - Light and the developing retina. AB - Retinopathy of prematurity (ROP) has increased in the United States in the past decade. Its resurgence has been attributed to advances in medical care which have increased the survival of infants less than 1000 g. Retinal immaturity and exposure to supplementary oxygen are generally accepted as the principal factors associated with ROP, however precocious exposure of the immature retina to light may also contribute. The preterm infant is routinely exposed for the duration of hospital stay to bright continuous light at levels which produce retinal damage in animals. A recent study has provided evidence implicating light in ROP. Preterm infants for whom the light levels were reduced had a lower incidence of ROP, compared to a similar group of preterms exposed to standard levels of nursery light. Given the problems of a non-randomized design, the results must be considered preliminary; however the findings are substantiated by parallel results in both hospitals studied and by an effect of exposure to light within the treatment group. Speculations regarding the mechanisms of light as a contributor to ROP include: alterations of retinal metabolism, cellular damage by phototoxicity, and the generation of free radicals. Mechanisms of phototoxicity are compatible with theories of oxygen toxicity. Light may not be necessary for ROP to occur, but it may increase the risk. PMID- 2209378 TI - The pathogenesis of retinopathy of prematurity as it relates to surgical treatment. AB - Our current surgical treatment for threshold retinopathy of prematurity (ROP) is based upon three concepts which emerged from morphologic and biochemical study of 250 pairs of whole eye donations obtained over a ten year period. 1) Spindle cells normally migrate and canalize to form inner retinal vessels, but when stressed, spindle cells secrete angiogenic factors. The clinical implication is that transretinal cryotherapy to the avascular retina is efficacious because it obliterates spindle cells. The number and timing of cryosessions are determined by the migration and kinetics of spindle cells. 2) Myofibroblasts originate from the shunt, are the major cellular component of extraretinal fibrovascular proliferation (EFP), and contract to produce retinal distortion and detachment. The clinical implication is that a second transretinal cryotherapy session should obliterate the shunt and the EFP, and should eliminate the source of retinal traction. 3) Anterior ocular growth occurs exponentially during the period when ROP develops and is treated. The clinical implication is that a prophylactic scleral buckle supports the fixed surface area of the developing retina while the choroid and sclera enlarge anteriorly. Retinal distortion produces misaligned photoreceptors, and retinal detachment results in rapid retinal death. PMID- 2209379 TI - Retinopathy of prematurity: prevalence and treatment over a 20 year period at Pennsylvania Hospital. AB - This paper presents the results of a 20 year survey of ROP among less than or equal to 2000 g BW infants cared for at Pennsylvania Hospital. It relates changes in perinatal care and nutrition, survival rates, and serial serum E levels with incidence and severity of ROP. It includes our protocol for monitoring E nutrition so as to optimize its effectiveness at physiologic serum levels for prophylaxis for ROP. Also presented are the promising results of our experience with vitamin E at pharmacologic serum levels as a treatment for severe ROP (defined as in the Cryo ROP Trial). These indicate the need for a multicenter trial to assess the effect of pharmacologic Vitamin E therapy as an alternative or supplement to therapy of severe ROP with laser or cryo surgery. PMID- 2209381 TI - Retinopathy of prematurity (ROP): optimal timing of clinical evaluation and standard procedures. AB - The authors present the protocol currently used in their institution for initial and follow-up evaluation of infants at high risk for developing retinopathy of prematurity (ROP). After topical anesthesia and lid speculum insertion, the examination is carried out using an indirect binocular ophthalmoscope with a +20 or +28-diopter lens. Mydriasis is achieved by instilling one drop of 1% tropicamide, followed by one drop of 0.5% tropicamide + 2.5% phenylephrine 15 minutes later and after an additional 15 minute interval, another drop of 1% tropicamide. If mydriasis is insufficient after one hour, one drop of a 0.5% tropicamide-5.0% phenylephrine solution may be instilled. The initial examination is performed between the third and fourth weeks of life. If any areas of retinal immaturity are found, the examination is repeated every other week and, later, every three to four weeks, until vascularization has reached the ora serrata. Should any sign of ROP be present during the first examination, the patient is examined weekly or every other week depending on the severity of clinical findings. PMID- 2209380 TI - Incidence, severity and time course of ROP in a randomized clinical trial of vitamin E prophylaxis. PMID- 2209382 TI - Echographic findings in infants with ROP. AB - The authors, before starting the discussion about ultrasound findings in infants with ROP, present a review of the history of ultrasound in this disease. Early A scan reports are mentioned while the B-scan literature from 1984 to 1988, consisting of seven papers, is reviewed extensively. The most important echo patterns in the various stages of the disease are described along with the most intriguing ones. There is disagreement as to whether it is always possible to show by echography if the retina is in place or not. This is due to the fact that the acoustic properties of the retina seem sometimes to change as time goes by and is quite independent of any technical difficulties which are still very great and the know-how of the examiner. PMID- 2209383 TI - Results of U.S. randomized clinical trial of cryotherapy for ROP (CRYO-ROP). AB - Twenty-three centers collaborated in this prospectively designed study involving infants born weighing less than 1251 grams. Patients examinations began 4 to 6 weeks from birth. For entry into the study, two investigators had to agree that an eye had developed stage 3 ROP involving a threshold number of at least 5 contiguous or 8 total clock hour sectors of zone 1 or 2, and 'plus' disease to a degree specified by a standard photograph. Cryotherapy was lightly applied to the avascular zone between the ridge of ROP and the ora serrata, in an average of about 50 separate spots. Outcome was determined 3 and 12 months following randomization, by means of masked readings of fundus photographs. Preliminary results were published in the Archives of Ophthalmology, Vol. 106, pp. 471-479, 1988. In these results from 172 of the 291 study patients, 43.0% of the control eyes had an adverse outcome (defined as retinal detachment, macular fold, or retrolental mass), as compared to 21.8% adverse outcome for eyes that received cryotherapy. PMID- 2209385 TI - The rationale for cryotherapy with a prophylactic scleral buckle for Zone I threshold retinopathy of prematurity. AB - Our current surgical protocol for Zone I threshold retinopathy of prematurity (ROP) has evolved over 15 years and is rationalized by increasing knowledge of two pathologic processes of ROP: 1) angiogenic stimulation of spindle cells (clinically invisible) near the vitreal surface of the avascular retina; and 2) tractional forces of myofibroblasts [clinically visible as extraretinal fibrovascular proliferation (EFP)] in the vitreous overlying the vascular retina. These two pathologic processes occur concomitantly with normal anterior ocular growth with a constant optic disc-macular distance. Our current surgical protocol for Zone I threshold ROP, involves complex surgeries to achieve success defined as a macula which always remains anatomically attached, but which may be distorted or ectopic. This protocol requires cryotherapy in at least two sessions. The first is to the avascular retina to destroy spindle cells. The second is to the EFP to destroy myofibroblasts and to the shunt to eliminate the site of origin of myofibroblasts. The protocol also requires the concomitant placement of a prophylactic scleral buckle to allow formation of a new complete ora serrata while remnant myofibroblasts contract and while anterior ocular growth continues. PMID- 2209384 TI - Critical mass retinopathy of prematurity: what is it and what can you do about it? AB - This paper presents a summary of my experience with treatment of 41 patients with retinopathy of prematurity. From November, 1976, to June, 1988, 76 eyes with Stage 3b, 3c, and Stage 4 ROP had treatment to the ridge-EFP complex, the avascular retina, or both locations. Cryotherapy was used in all eyes, with two having Argon laser photocoagulation as well. These studies have shown that: 7.9% of all treated eyes had Grade III to V RLF; the optimal timing of intervention is recommended during progression of Stage 3b+ ROP; the optimal location of treatment appears to be the avascular retina with the ridge-EFP perhaps as effective but the treatment of both areas simultaneously is to be avoided due to an increased occurrence of grade II RLF and macular pigment epitheliopathy in those eyes so treated. A comparison of results of four major studies indicate that the U.S. Cryo-ROP Study has three times the rate of Grade III to V RLF, probably because of intervention after the accumulation of excessive quantities of Stage 3b and/or 3c ROP. PMID- 2209386 TI - [Regulation of erythrocyte membrane resistance to extreme effects of tris-(2 hydroxyethyl)ammonium salt of 4-fluorophenylsulfonylacetic acid]. PMID- 2209387 TI - [Types of habitat for parasitic and free-living organisms]. PMID- 2209388 TI - [Treatment of cells with para-aminobenzoic acid reduces the number of DNA breaks induced by chemical mutagens]. PMID- 2209390 TI - [Identification of specific hypoxic protein from human lymphocytes]. PMID- 2209391 TI - [The effect of regenerated minced muscle tissue autotransplanted under the skin on the recovery of rat hair]. PMID- 2209392 TI - [Molecular karyotyping of biological species Saccharomyces cerevisiae, S. paradoxus, and S. bayanus]. PMID- 2209389 TI - [Rearrangement of the structural organization of DNA liquid crystals induced by natural compounds]. PMID- 2209394 TI - [Classification of the endogenous regulatory oligopeptides based on the primary structure]. PMID- 2209393 TI - [Photodynamic cell injury in the red and IR-absorption bands of endogenous oxygen]. PMID- 2209395 TI - [Phage infection of populations of motile bacteria as a model for the study of virus resistance of multicellular systems with heterogeneous growth cycle phases]. PMID- 2209396 TI - [Complexes of viruses with synthetic polyelectrolytes and their interaction with antibodies]. PMID- 2209397 TI - [Characteristics of neurotic reactions in cats and the role of beta-endorphin conjugates in their control]. PMID- 2209398 TI - [Changes in physiological processes during starting period of hibernation in warm blooded animals]. PMID- 2209399 TI - [The use of the TGATG vector for expression in Escherichia coli cells of cloned cDNA copy of human interleukin-1beta gene]. PMID- 2209401 TI - [Electrophysiologic and clinical characteristics of fascicular ventricular tachycardia (a report of 15 cases)]. PMID- 2209400 TI - [Effects of nifedipine on global and regional function of the left ventricle in patients with acute myocardial infarction]. PMID- 2209402 TI - [Adenosine deaminase inhibitor (EHNA) on ischemia-reperfusion injury in isolated perfused rat hearts]. AB - The effects of Erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) on Langendorff perfused rat hearts subjected to ischemia-reperfusion injury were studied. Results showed that EHNA can inhibit the increase of cardiac resting tension during ischemia period and decreasing the incidence of ventricular fibrillation and its duration. The contraction amplitude, resting tension and heart rate could be recovered to preischemic level, and the coronary flow even greater than before. The authors thought that EHNA can block the breakdown of adenosine to inosine and hypothanxine, and, therefore, cut off the pathway and production of oxygen free radicals during ischemia-reperfusion injury. PMID- 2209403 TI - [Electrophysiologic study of ischemic ventricular arrhythmia]. AB - Epicardial composite electrode and isochronal mapping were used in this study to detect ventricular late potentials and ventricular activity sequence during sinus rhythm and ventricular tachycardias. 20 dogs were studied before and during acute ischemia induced by coronary artery ligation, 11 dogs 3-7 days after two-stage ligation of the left anterior descending coronary The effect of lidocaine and verapamil on VLP and reentrant ventricular arrhythmias was studied. The results demonstrated that: (1) Ventricular arrhythmias occurred right after ligation and 3-7 days later after ligation were related to the reentry in infarct myocardia zone; (2) The inhomogeneous conduction and dispersive refractory period provided a suitable milieu for reentry; (3) Reentrant excitation always occurred in a figure 8 configuration and delayed depolarization and continuous activation were reflected as VLPs at composite electrode; (4) Lidocaine in therapeutic dose prolonged the VLPs and interval of V-VLP. The effect of lidocaine on the ischemic zone was directly related to its ability to abolish reentrant ventricular arrhythmias; (5) Verapamil shortened the VLPs and interval of V-VLP, so the action of slow-response action potentials could not be excluded. Further study should be performed in order to demonstrate the precise mechanism of VLP. PMID- 2209405 TI - [Long-term treatment of congestive heart failure with captopril]. PMID- 2209404 TI - [Changes in renin activity in patients with acute myocardial infarction]. PMID- 2209406 TI - [Left ventricle diastolic function in hypertensive patients and responses to captopril]. AB - The LV diastolic function of 37 cases with primary hypertension were studied by measuring the diastolic filling blood stream at mitral orifice using pulsed Doppler echocardiography. 30/37 (81%) patients were found to have impaired LV diastolic function as compared with 30 normals of a group at similar age. After 4 weeks of oral captopril treatment in 20/37 patients, BP dropped in 19/20; LV diastolic function improved in 75-80%; left ventricular mass also regressed in 16/20 captopril treated patients (210 +/- 62 vs 171 +/- 46 g, P less than 0.01). It showed that captopril is not only effective in lowering blood pressure but also in improving the impaired LV diastolic function. PMID- 2209407 TI - [Effect of enalapril in patients with essential hypertension]. AB - In a randomized, blind trial, enalapril and captopril were compared in 479 patients with essential hypertension. The results showed that both enalapril and captopril had similar effects on the blood pressure. The response rate was 77.8% with enalapril and 70.4% with captopril. Blood pressure lowered 2.68/1.59 kPa (20.1/11.9 mmHg) in enalapril group versus 2.44/1.43 kPa (18.3/10.7 mmHg) in captopril group. No serious side effects were observed and both enalapril and captopril were well tolerated. Thus, enalapril and captopril appear equally effective and safe in patients with essential hypertension and enalapril is better accepted by patients because of its longer duration of antihypertensive activity. PMID- 2209408 TI - [Local angiotensin in the myocardium of aging rats]. PMID- 2209409 TI - [Primary dissection of coronary artery (a case report)]. PMID- 2209410 TI - [Changes in plasma TXB2 and 6-keto-PGF1 alpha and left atrial thrombosis in mitral stenosis]. AB - This study was performed to determine the relationship between plasma concentration of thromboxane B2 (TXB2), 6-keto-prostaglandin F1a and atrial thrombosis in patients with mitral stenosis (MS). By radioimmunoassay and pathological examination, peripheral plasma TXB2 level was remarkably higher in patients with MS and persistent atrial fibrillation (AF) than in patients with MS but without AF (P less than 0.01). Plasma TXB2 level was significantly higher in patients with than in those without atrial thrombosis (P less than 0.05). There was no significant difference in plasma 6-keto-PGF1 alpha, plasma prostanoids level in peripheral venous blood correlated closely with that in left atrial blood. Patients with high plasma TXB2 level had a greater incidence of microthrombosis. PMID- 2209411 TI - Safety and side-effects of buprenorphine in the clinical management of heroin addiction. AB - Sublingual buprenorphine (8 mg) was administered to heroin-dependent addicts daily for 18 days and continued from day 19-day 36 either daily or on alternate days. Final data are reported on 18 subjects. The number of self-reported symptoms reviewed as potential adverse drug reactions ranged from 1 to 88 per participant. None was considered to be related definitely to the study medication, and there were no reporting differences between the two dosing regimens. Forty-five reactions were considered probably related to buprenorphine: sedation/drowsiness (three reports) and constipation (42 reports). It was concluded that these were anticipated drug effects rather than adverse reactions. Although some participants showed increases in serum aminotransferase levels, those increases could not be directly attributed to buprenorphine. We conclude that buprenorphine was well tolerated, but further study is needed in this population to delineate the possible attributable risk of the drug to hepatic dysfunction in this population. PMID- 2209412 TI - Effect of acute injections of ethanol on lipid and protein-bound sialic acid in mice of different ages. AB - Mice of different age groups (weanling, young adult and aged) were tested for changes in brain lipid- and protein-bound sialic acid (SA) 2 h after ethanol (2 g/kg, i.p.), either as a single dose or after binge dosing of five repeated doses of ethanol spaced 2 h apart. The results clarify our earlier demonstrations that acute ethanol can reduce whole brain SA. Ethanol generally decreased SA of both gangliosidic and glycoprotein origin, with the effect varying with number of doses and mouse age. Single-dose ethanol decreased both lipid-bound and protein bound SA in young adults and decreased lipid-bound SA in aged mice. There was no effect on lipid-bound SA in weanlings, but weanlings did have a 72% decline in protein-bound SA. Repeated injections in young adults did not cause the SA decrease seen with acute injection. In both weanling and aged mice, however, repeated injections did cause large decreases in both lipid- and protein-bound SA. Small, but statistically significant, changes also occurred in free SA. Ethanol increased free SA in singly-dosed young adults and in multiply-dosed aged adults, while causing a distinct decrease in singly-dosed weanlings. PMID- 2209413 TI - A note on the use of statistical models in epidemiologic research on illicit drug use. AB - This essay aims to stimulate thinking or to remind readers about the shortcomings of standardized regression coefficients and related statistical measures in epidemiologic research on illicit drug use. This is accomplished primarily with a set of examples based on simulated epidemiologic data in which the standardized regression coefficient is shown to co-vary dramatically with frequency of the outcome variable. The basic thrust of this critique of commonly used regression models is not new; it has appeared elsewhere several times. Nevertheless, in epidemiologic research on illicit drug use, there is a continuing use of standardized regression coefficients and other margin-sensitive statistical measures without comment on their shortcomings. Thus, a specific critique with illustrations might have value. PMID- 2209414 TI - Intravenous drug abusers with antisocial personality disorder: increased HIV risk behavior. AB - Intravenous drug abuse is strongly associated with HIV transmission and with having a diagnosis of Antisocial Personality Disorder (ASPD). While the co occurrence of intravenous drug abuse and ASPD is related to poor drug abuse treatment outcome, little is known about the contribution of ASPD to the intravenous drug abusers (IVDAs) level of HIV risk. The present study related the diagnosis of ASPD with specific drug use behaviors associated with high risk of HIV transmission. Subjects (N = 100) were intravenous drug abusers who volunteered for an HIV risk assessment study. Subjects with ASPD reported significantly higher rates of injection-equipment sharing and shared with significantly more people than IVDAs without ASPD. PMID- 2209415 TI - Relationship between masculinity and feminity in drinking in alcohol-related behavior in a general population sample. AB - The relationship between gender-related personality traits, on one hand and drinking, permissiveness towards drinking, and social as well as personal problems associated to drinking on the other, was studied in a general population sample from the City of Morelia, Mexico. Four gender-related traits scales were used for measuring assertive and aggressive masculinity and affective and submissive feminity, in addition to a standardized questionnaire for assessing drinking and other associated behavior. Some of the main results showed that people with high scores in affective feminity were less willing to allow drinking. Men who adopted a submissive feminine role and women with high masculine aggressive scores were more permissive as regards drinking. Among men, assertive masculine and affective feminine traits were more characteristic among those who drank than among abtainers. Drinking among women was related to liberal attitudes towards drinking and to aggressive masculinity. As regards the number of drinks consumed per month, assertive masculinity and liberal attitudes among men and affective feminity and liberal attitudes among women predicted the number of drinks. Affective feminity was negatively related to drinking. Regarding drinking-associated problems, frequency of drunkenness and submissive feminity among males predicted greater personal and social problems. Among women, drunkenness frequency and number of drinks were the most significant predictors. Contrary to what has been found in other countries, gender was a better drinking predictor than gender-related personality traits. PMID- 2209416 TI - Attitudes of a sector of the Arab-Muslim population in Kuwait towards alcohol and drug misuse: an objective appraisal. AB - The attitude of a sample of 1001 Arab Muslims living in Kuwait towards alcohol and drug misuse was examined by using a 30-item questionnaire. Eighty percent condemned drug misuse, 93.6% thought it was a contravention of Muslim religious teachings, yet 90% held an enlightened attitude compared to only 26% that chose the punitive attitude. The older generation, the less educated, females and Non Kuwaiti Arabs were less likely to be sympathetic towards substance misusers. These findings while indicating the sample's strong religious condemnation of substance misuse demonstrated the adoption of Western concepts of care especially by the younger educated Kuwaiti males. Indirect evidence of drug misuse and smoking in the sample may be inferred from the low rates of denunciation of such behaviours. PMID- 2209417 TI - Use of psychoactive substances among male secondary school pupils in Egypt: a study on a nationwide representative sample. AB - The present work is part of a series of epidemiological studies the main aim of which is to shed light on the extent and patterns of the use of substances among various sectors of the Egyptian population. A standardized questionnaire with established item re-take reliabilities was administered to 14,656 male secondary school pupils constituting a 4% representative sample of the whole population of Egyptian secondary school boys. Demographic and drug-related findings are discussed. Among the reported results the following are deemed of special interest: (1) Percentages of arts students who smoke tobacco, ever use prescription psychotropic substances, narcotics and alcohol consistently exceed their counterparts studying science and mathematics. (2) Ages of onset for the whole menu of substances range between 12 and 16 years. (3) Those among the experimenters who admitted continuing to take drugs ranged between 8% (for alcohol) and 21.41% (for synthetic drugs). (4) Significantly more urban than rural students smoke tobacco, and try cannabis and alcoholic beverages. (5) There is a strong association between exposure to drug culture and drug taking, confirming what we repeatedly reported previously. (6) More users than non-users tend to see drug consumption as either harmless or even useful. (7) Differentiation should be made between vulnerable and non-vulnerable non-users. Vulnerable non-users share with actual users a number of components of a common "drug ideology". (8) There are very significant correlations between drug taking and various aspects of misconduct verging on delinquency. PMID- 2209418 TI - The growth of treatment research in alcohol and drug use disorders: a computerized literature search. AB - Index Medicus was searched to compare the number of articles on treatment trials for alcohol and for non-alcohol drug use disorders (abuse, dependence, withdrawal, intoxication, etc.) to that of two control conditions--anxiety and obesity--for the period 1967-1988. Over the entire 22 years, the number of articles for alcohol use disorders increased an average of 2.7 articles every 2 years and 5.8/2 years for drug use disorders compared to 5.7/2 years for obesity and 5.8/2 years for anxiety disorders. Over the most recent 8 years, articles for alcohol use disorders increased 7.7/2 years and for drug use disorders 7.9/2 years compared to--2.9/2 years and 12.0/2 years for obesity and anxiety disorders. The proportion of articles that cited using only pharmacotherapy decreased over time; however, studies of alcohol and drug withdrawal continue to almost exclusively use pharmacological therapies. We conclude that treatment research in alcohol and drug use disorders is growing as rapidly as that in similar psychological and psychiatric conditions and that such growth is not due to a focus on pharmacological treatments. PMID- 2209419 TI - What do opiate addicts and cigarette smokers mean by "craving"? A pilot study. AB - There is general agreement that the term 'craving' requires clarification. This present report presents a pilot study in which groups of opiate addicts and cigarette smokers completed a brief rating scale to describe the frequency and intensity with which they had certain feelings while craving for their own drug of dependence. Craving was reported as being a dysphoric state and opiate addicts described more frequent and more intense dysphoric feeling while craving. Despite the difference in mean scores there were some similarities in the overall profile of scores in the two groups. Implications of these findings are discussed. PMID- 2209420 TI - The effect of abstinence in alcoholics of erythrocyte gangliosides. AB - The pattern of gangliosides in membranes of erythrocytes was examined in healthy and in alcoholic subjects on the second and on the 28th day of detoxification therapy. The GM3 and GD3 fraction were decreased significantly in alcoholics on the 2nd day. After 4 weeks of abstinence all changes had returned to the level of healthy subjects. PMID- 2209421 TI - [Primary hyperparathyroidism. A disease picture has changed]. AB - Data were retrospectively analysed on 544 consecutive patients (362 females and 182 males, mean age 53.6 [2 weeks and 86 years]) who had been operated on for primary hyperparathyroidism between 1965 and 1989. During this period the rate of renal, bone and intestinal complications decreased from 90% in the first 5 years to 29% in the last 5 years. Organ manifestations and hypercalcaemia were often combined (70% in the early period, 30% now). The proportion of those with an asymptomatic course gradually and continuously rose to 21% now. The patients' average age at diagnosis rose from 46 +/- 10 to 58 +/- 14 years. Serum calcium concentrations in the last few years averaged 3.1 mmol/l, as high during the last few years as at the beginning of the period. Age, serum calcium concentration and parathyroid weight of the asymptomatic patients did not differ from those of the group as a whole. PMID- 2209422 TI - [Relationship of the left ventricular wall thickness to the degree of late microvascular complications in diabetes mellitus type I]. AB - Left-ventricular wall thickness, measured by echocardiography, was determined in 111 normotensive diabetics (63 men and 48 women; mean age 26 +/- 9 years; diabetes duration 13.5 +/- 6.2 years) and 91 comparable control subjects. The interventricular septum was significantly thicker in diabetics than in controls: systolic 13.3 +/- 2.3 mm, diastolic 9.2 +/- 2.2 mm vs. systolic 12.5 +/- 2.1 mm and diastolic 8.9 +/- 1.7 mm (P less than 0.05). Posterior wall thickness measurements were: systolic 15.8 +/- 2.2 mm vs 14.6 +/- 2.0 mm (P less than 0.001), diastolic 9.5 +/- 1.8 mm vs 8.4 +/- 1.3 mm (P less than 0.01). Left ventricular wall thickness increased stepwise with increasing severity of microvascular complications (retinopathy, nephropathy, neuropathy). There was a moderately close correlation between blood pressure values and the degree of microvascular complications (r = 0.49, P less than 0.01). These correlations indicate that increases in wall thickness are diabetes specific, but may be influenced by the level of blood pressure. PMID- 2209423 TI - [Pseudofluorosis: psychologic aspects of environmental pollution]. AB - A middle-aged woman who had been living in close surroundings of a fluorine emitting factory for many years, was examined because she claimed to be suffering from skeletal fluorosis. Radiological, histological and laboratory findings did not give evidence of fluorosis. Fluoride concentrations were normal in samples of blood, bone, pooled urine, nails and hair. Even this proof to the contrary did not shake her conviction of many years that she was suffering from fluorosis. Thus, psychological aspects have to be considered in the assessment of health implications of pollutants. PMID- 2209424 TI - [Clinical significance of steroid hormone receptor determination in breast carcinoma tissue]. PMID- 2209425 TI - [Sports and the digestive tract]. PMID- 2209426 TI - [Pseudobulbar paralysis]. PMID- 2209427 TI - [Postprandial symptoms caused by hypoglycemia?]. PMID- 2209428 TI - [Bronchoscopic diagnosis of pneumonia with quantitative microbial count determination]. AB - Micro-organism counts of bronchoalveolar lavage (BAL) and microbrush swabs were obtained from 40 immunocompetent (group A) and 23 immunosuppressed (group B) patients with nosocomial pneumonia, and a control group consisting of 40 patients with noninfectious pulmonary infiltrates. The sensitivity of BAL was high: 77.5% for group A and 85% for group B, while microbrush swabs gave many false-negative results. Microorganism counts were at or above 10(5) cfu/ml in 32 of 44 examinations (bacterial or mycotic pneumonia), but in only one case of the control group. Lower counts were obtained with localized infection and microorganisms difficult to culture (Aspergilla and Legionella). Granulocytosis in the lavage fluid was demonstrated in 38 of 41 patients with bacterial pneumonia and thus proved useful in the differential diagnosis. In 16 of 40 immunocompetent and 13 of 23 immunosuppressed patients with pneumonia the results were therapeutically of importance. Thus, invasive diagnosis is indicated especially in complicated or treatment-resistant nosocomial infections. PMID- 2209429 TI - [Sweet's syndrome after T-lymphoblastic lymphoma and before the manifestation of a secondary acute myeloid leukemia]. AB - Thirty-two months after the diagnosis and treatment of a T-lymphoblastic lymphoma with bone marrow involvement had been made in a 30-year-old patient, he developed fever up to 40 degrees C during maintenance treatment with methotrexate and 6 mercaptopurine. Later there were tender, blue-red skin eruptions, leukocytopenia (1.4 x 10(9)/l) and thrombocytopenia (29 x 10(9)/l). Histological examination of a skin biopsy revealed acute febrile neutrophilic dermatosis (Sweet's syndrome). Bone marrow biopsy revealed hyperplastic myelopoiesis. There was no evidence for acute myeloid leukaemia or lymphoma recurrence. After the maintenance treatment had been discontinued, treatment with methylprednisolone, 60 mg, was begun. The signs of Sweet's syndrome regressed, but thrombocytopenia and mild leukocytopenia remained. Six months later it was found by morphological and immunological tests that he had acute myeloid leukaemia without any chromosomal abnormalities. There was still no evidence for a recurrent T-lymphoblastic lymphoma. PMID- 2209431 TI - [Diagnosis of medullary thyroid gland carcinoma]. PMID- 2209430 TI - [Osteoid osteoma at the end of the phalanx of the big toe]. AB - A 20-year-old man with persistent pain in the left big toe associated with broadening, thickening and discolouration of the toenail had been treated unsuccessfully for 21 months by surgical measures (wedge excision, avulsion of the nail) and local applications (antibiotics, antimycotics, disinfectants). A radiograph of the left big toe showed an area of calcification 0.5 cm in diameter at the base of the terminal phalanx. It was surrounded by a narrow zone of transradiancy and projected upwards above the margin of the bone. Among the diagnostic possibilities were osteomyelitis and osteoid osteoma. Biopsy revealed the latter, and the patient was cured by "en bloc" resection of the tumour. This case shows that abnormalities of nail growth of the kind commonly associated with paronychia may occasionally be due to a neoplastic lesion in the terminal phalanx. PMID- 2209432 TI - ["Success security." A sensible standard for describing the validity of diagnostic measurements]. PMID- 2209433 TI - [How problematic is the dental material amalgam?]. PMID- 2209434 TI - [Intestinal spirochetosis in HIV infection: prevalence, isolation and morphology of spirochetes]. AB - The prevalence of intestinal spirochaetosis was investigated in 39 HIV-positive homosexual males (mean age 39 [24-65] years) in different stages of HIV infection (3 with the lymphadenopathy syndrome, 8 with AIDS-related complex and 28 with AIDS). Biopsies for cultural and histological demonstration of spirochaetes were obtained during routine ileoscopies. At the time of examination 35 of the 39 patients had intestinal symptoms. 27 patients had had no previous antimicrobial treatment. In 12 of the 27 previously untreated patients with intestinal symptoms spirochaetes were demonstrated, to different extent, from the terminal ileum to the rectum, while the treated group of eight and the control group of four were negative. There were no significant inflammatory changes histologically. Treatment with metronidazole in most cases improved symptoms. In their ultrastructure the microorganisms showed several complete convolutions, cone shaped cell endings, cell length of 4-18 microns, cell diameter of 0.21-0.35 microns and five subterminal flagella. Morphological considerations favour the inclusion of these microorganisms in the genus Treponema rather than Brachyspira. PMID- 2209435 TI - [Cardiomyopathy in progressive muscular dystrophy]. AB - A dilated cardiomyopathy with clear signs of left-ventricular functional abnormalities occurred in a 21-year-old man with known Duchenne's progressive muscular dystrophy. Echocardiography and magnetic resonance imaging delineated the regional disorder of ventricular wall motion and defined its segmental extent. With neither method was it possible to analyse texture with demonstration of differential regional involvement. As a noninvasive method echocardiography is suitable for diagnosing Duchenne's cardiomyopathy and monitoring its progression. PMID- 2209436 TI - [Diagnosis of hairy cell leukemia]. PMID- 2209438 TI - [Left anterior hemiblock]. PMID- 2209437 TI - [Refusal by health care personnel to carry out intravenous injections]. PMID- 2209439 TI - [Thrombolysis in resuscitated patients with pulmonary embolism]. PMID- 2209440 TI - [Care of an indwelling peripheral catheter]. PMID- 2209441 TI - [Anxiety before gastrointestinal endoscopy--a significant problem?]. AB - 98 consecutive patients (40 men, 58 women; mean age 49 [17-83] years) who had been referred for outpatient gastroscopy or colonoscopy were questioned beforehand regarding their anxiety about the procedure, its causes and how it could be dispelled. Two thirds of them (67%) stated that they felt anxiety about the investigation; almost half of them (46%) felt very great or "terrible" anxiety. 55% of the patients had been fully informed about the nature of the procedure. 69% of the women and 48% of the men had previously experienced gastroscopy or colonoscopy. The reasons for their anxiety were varied. One quarter of those questioned (24%) had had unpleasant experiences during previous endoscopies; others had been alarmed by rumours about endoscopy (22%), and some were less worried about the procedure itself than about what it might reveal (24%). Almost two thirds (63%) wanted a tranquilizing injection. Other methods for dispelling anxiety, such as detailed information about the procedure (21%), a calm, relaxed atmosphere (19%) or the presence of a relative at the endoscopy (7%) were claimed for in a limited way. However, 37% very much wanted to watch the endoscopy on the television monitor. The findings show that the number of patients who experience anxiety before undergoing endoscopy is alarmingly great, and that more energetic measures are necessary to relieve their fears and worries. PMID- 2209442 TI - [Inoculation failure following hepatitis B vaccination. The effect of additional vaccinations]. AB - One to three repeat vaccinations were undertaken in 63 persons (32 males, 31 females; mean age 29 [17-59] years) who had not or inadequately responded to basal immunization with hepatitis B vaccine (47 non- and 16 hyporesponders). After re-vaccination, 12 of the 47 nonresponders and 11 of 16 hyporesponders formed specific antibodies against hepatitis B surface antigen, anti-HBs, at concentrations above 10 IU/l. Six of 14 persons who had not responded to the first repeat vaccination reached anti-HBs concentrations above 10 U/l after a further injection. Vaccination response was age-dependent. The median age of those subjects who responded to the first re-vaccination was 27 (19-45) years, while the non-responders' median age was 34 (22-59) years (P less than 0.05). Re vaccination also raised initially low anti-HBs values. These results indicate that some of the nonresponders can obtain reliable protection by revaccination(s). PMID- 2209443 TI - [Variant (Prinzmetal's) angina with diffuse coronary spasm without coronary sclerosis]. AB - A 49-year-old man developed, over a period of three years, progressively more frequent nocturnal attacks of angina and palpitations. Exercise electrocardiogram was negative. 24-hour Holter monitoring revealed ventricular extrasystoles and tachycardia with ST segment elevations. The dominant left coronary artery, which was free of atherotic changes, went into diffuse spasm after ergonovine administration, accompanied by angina and ventricular extrasystoles. Registration of spontaneous ischaemia confirmed the diagnosis of variant (Prinzmetal) angina. Administration of twice daily 90 mg diltiazem retard and once daily 120 mg isosorbide dinitrate retard at night ended the spasms and with it the attacks of angina and the arrhythmias. This case illustrates that typical angina and ventricular tachyarrhythmias can be caused by spontaneous coronary spasms, even in the presence of normal exercise ECGs and coronary angiograms. If coronary artery spasms are not detectable by ECG, the ergonovine test may further the diagnosis. PMID- 2209445 TI - [The therapy of hairy-cell leukemia]. PMID- 2209444 TI - [Colonic carcinoma localized in the chest in enterothorax due to congenital diaphragmatic hernia]. AB - A 51-year-old man with congenital diaphragmatic hernia and enterothorax was found to have persisting leucocytosis (25,000/microliters), diarrhoea and weight loss (20 kg). Computed tomography (CT) revealed intrahepatic space-occupying lesions. CT-directed needle biopsy demonstrated adenocarcinoma metastases. Colon contrast enema was ambiguous. Since no primary tumour had been found, ambulatory treatment with 5-fluorouracil was started. After initial improvement diarrhoea and obstipation alternated so that the patient finally gave permission for coloscopy to which he had not consented at first. It revealed a carcinoma of the colon located in the thorax about 10 cm oral to the left colonic flexure. Progressive ileus necessitated an ileodescendostomy for palliation. The patient died three months later while on symptomatic treatment. PMID- 2209446 TI - [Hepatitis B protective inoculation. The problem of inadequate anti-HB production]. PMID- 2209447 TI - [Bone marrow transplantation in the concept of the step-by-step therapy of refractory or recurrent Hodgkin's lymphoma]. PMID- 2209448 TI - [The confidentiality duty of the treating physician vis-a-vis genetic counseling centers]. PMID- 2209449 TI - [Paroxysmal hypokalemic paralysis]. PMID- 2209450 TI - [The risk of spontaneous abortion and the reproductive medical anamnesis]. PMID- 2209451 TI - [A review of the diagnostic possibilities of illegal drug administration in slaughtered animals and meat inspection]. AB - A review of possible residues of selected antibacterial substances, hormones, beta-agonists, thyreostatics and tranquillizers in meat is given in this paper. Showing their application mode and the few clinical effects and pathological findings, the collection of samples becomes very important. For each group of substances tissues or body-fluids are proposed as samples. With modern analytical detection methods residues in food of animal origin can be demonstrated at levels of micrograms/kg. The detection of the above mentioned substances could be supported by a well-aimed sampling and the illegal use can be diminished. PMID- 2209452 TI - [Pathologico-anatomic findings in thymus gland and female sex organs of slaughtered calves after treatment with anabolically effective substances]. AB - The authors describe the pathomorphological findings in the thymus, female genital organs and Bartholin's glands in 413 slaughter calves with white skeletal musculature. Anabolic substances like oestrogens, androgens, and corticosteroids had most likely been administered to a total of 302 of these animals. In all cases thymic atrophy was present. Microcysts of the ovaries were seen in 17% of the cases, mucometra of the uterus in 49%, hydrometra in 23%, and squamous metaplasia in Bartholin's glands in 15%. PMID- 2209453 TI - Pharmacokinetics and tissue residues of kitasamycin in healthy and diseased broilers. AB - The pharmacokinetics of kitasamycin after intravenous and oral administration in a dose of 300 mg/kg b.wt. was studied in 18 healthy and 18 Salmonella gallinarum naturally infected chickens. The tissue residue of the studied antibiotic was estimated in 36 normal chickens when it was given orally for 7 successive days. Therapeutic level of kitasamycin was achieved after 15 minutes and persisted for 20-22 hours after its oral administration. Higher serum kitasamycin concentrations were recorded in Salmonella gallinarum infected chickens. The elimination half-life of kitasamycin calculated after single intravenous injection was 9.03 hours in diseased chickens corresponding to 3.74 hours in healthy birds. The body clearance was significantly reduced in diseased chickens (23.86 ml/kg/min) when compared to that in normal ones (62.03 ml/kg/min). Kitasamycin treated broilers should not be slaughtered before 3 days from the last dose as it was detected only in bile and caecum at that time but not in edible tissues. PMID- 2209454 TI - [Occurrence and significance of different Campylobacter types in domestic animals in Hungary]. AB - Experiences, including results of original experimental work on Campylobacter fetus, C. jejuni and C. coli induced diseases of cattle, sheep, dogs, rabbits poultry and men in Hungary are reviewed. Out of 31 cases of abortion in cows 29 (93.5%) were causes by C. fetus subsp. venerealis and only one case each (3.2%) by C. fetus subsp. fetus and C. jejuni, respectively. Out of the 29 strains of C. fetus subsp. venerealis, 26 belonged to serogroup 01 (A) and only 3 to serogroup 02 (B). Campylobacter abortions in sheep flocks were caused in 18 cases (78.3%) by C. fetus subsp. fetus and in 5 cases (21.7%) by C. jejuni. The latter strains belonged to Penner's serogroup 1 (6 strains), 5 (4 strains) and 8 (5 strains), respectively. In scouring dogs 12.7% of the cases were caused by C. jejuni. The same pathogen caused diarrhoea also in young rabbits. Isolated strains belonged to serogroup 2. In cases of Campylobacter hepatitis of laying hens, egg production has been reduced by 8 to 15% for 2 to 3 weeks. Row poultry meat represents often the source of infection for men. The 32 strains of C. jejuni isolated from faecal samples of men affected with diarrhoea belonged to 12 serogroups. PMID- 2209455 TI - Pharmacokinetic profile of cefotaxime in goats. AB - Cefotaxime was once administered in goats via intravenous, intramuscular and subcutaneous routes for determination of blood and urine concentration, kinetic behaviour and bioavailability. Following a single intravenous injection, the blood concentration-time curve indicated two compartments open model, with an elimination half-life value (t1/2 beta) of 22.38 +/- 0.41 minutes. Both intramuscular and subcutaneous routes showed lower values i.e. 38.64 and 69.58 minutes. The lower apparent volume of distribution of cefotaxime in goats than one liter/kg elucidated lower distribution in tissues than in blood. After intramuscular and subcutaneous injections peak plasma cefotaxime concentrations were 77.8 +/- 1.7 and 44.0 +/- 0.8 micrograms/ml at 29.6 and 40.4 minutes, respectively. The average bioavailability of cefotaxime given by intramuscular and subcutaneous injection was 1.08 and 1.25, respectively. The cefotaxime concentration remained in urine 24 hours longer after subcutaneous injection than after intramuscular administration. PMID- 2209456 TI - [Technological contributions of the Insemination Association of Neustadt/Aisch in the area of artificial insemination]. PMID- 2209457 TI - [Illustrated report: an unusual form of animal torture in street pigeons]. PMID- 2209458 TI - ["Little bells" in agricultural domestic animals]. PMID- 2209459 TI - The development of handedness in left/right asymmetry. AB - The development of handed asymmetry requires a special mechanism for consistently specifying a difference between left and right sides. This is to be distinguished from both random asymmetry, and from those left/right differences that are mirror symmetrical. We propose a model for the development of handedness in bilateral animals, comprising three components. (i) A process termed conversion, in which a molecular handedness is converted into handedness at the cellular level. A specific model for this process is put forward, based on cell polarity and transport of cellular constituents by a handed molecule. (ii) A mechanism for random generation of asymmetry, which could involve a reaction-diffusion process, so that the concentration of a molecule is higher on one side than the other. The handedness generated by conversion could consistently bias this mechanism to one side. (iii) A tissue-specific interpretation process which responds to the difference between the two sides, and results in the development of different structures on the left and right. There could be direct genetic control of the direction of handedness in this model, most probably through the conversion process. Experimental evidence for the model is considered, particularly the iv mutation in the mouse, which appears to result in loss-of-function in biasing, and so asymmetry is random. The model can explain the abnormal development of handedness observed in bisected embryos of some mammalian, amphibian and sub vertebrate species. Spiral asymmetry, as seen in spiral cleavage and in ciliates, involves only conversion of molecular asymmetry to the cellular and multicellular level, with no separate interpretation step. PMID- 2209460 TI - The parthenogenetic development of rabbit oocytes after repetitive pulsatile electrical stimulation. AB - Freshly ovulated rabbit oocytes were activated parthenogenetically by periodically repeated calcium stimuli generated by electric field pulses applied onto the plasma membrane. Electric field pulses of 1.8 kV cm-1 were delivered every 4 min for 1 h 30 min (22 double pulses) in a specially designed chamber. Before each pulse, the culture medium was replaced by an isotonic glucose solution containing 10 microM Ca2+. The effects of modulating the ionic stimuli (by changing the duration of EF pulse) on a postactivation reaction, and/or on the pre- and postimplantation development, were studied. The rate of activation increased progressively as the pulse duration lengthened. For 22 pulses of 200 microseconds, 13% of oocytes were activated versus 100% for 1200 microseconds. The uniformity of the parthenogenetic response was obtained when oocytes were exposed to a series of pulses within which the reduction of pulse duration followed a negative exponential law. The influence of such activating treatment on the preimplantation development was tested using two treatments of 22 pulses with a total pulse duration equal to 14,868 and 11,228 microseconds, respectively. For the weaker treatment, a lower proportion of embryos underwent compaction and those that compacted were irregular. In contrast, the majority of embryos resulting from the stronger treatment compacted and developed into blastocysts. The most significant result that emerges from this study is that the level of stimulation affects in vitro developmental potency after the third cleavage division. The postimplantation viability of parthenogenetic eggs was tested and the results showed that parthenogenetic rabbit embryos died at a similar stage of development to the parathenogenetic mouse embryos. But, in the present series, high implantation rates and embryonic development (66%) till day 10-11 of pregnancy were obtained after the appropriate pulsatile EF treatment of oocytes. The parthenogenetic fetuses were of smaller size than the controls, but the development of the trophoblast tissue was proportional to the development of the fetuses. Anomalies of fetuses were also observed. This study reveals that activation is not a time-limited event and that the type of activating treatment has a marked effect on the ability of the resulting parthenogenetic embryos to develop to the early postimplantation stages. The sustained alteration of the cytoplasmic activity provides a useful tool to study the function of embryonic or somatic nuclei introduced during the earliest stages of activation. PMID- 2209461 TI - Fusion between myoblasts and adult muscle fibers promotes remodeling of fibers into myotubes in vitro. AB - Muscle satellite cells are residual embryonic myoblast precursors responsible for muscle growth and regeneration. In order to examine the role of satellite cells in the initial events of muscle regeneration, we placed individual mature rat muscle fibers in vitro along with their satellite cells. When the satellite cells were allowed to proliferate, they produced populations of myoblasts that fused together to form myotubes on the laminin substrate. These myoblasts and myotubes also fused with the adult fibers. When they did so, the fibers lost their adult morphology, and by 8 days in vitro, essentially all of them were remodeled into structures resembling embryonic myotubes. However, when proliferating satellite cells were eliminated by exposure to cytosine arabinoside (araC), the vast majority of fibers retained their adult shape. Addition of C2C12 cells (a myoblast line derived from adult mouse satellite cells) to araC-treated fiber cultures resulted in their fusion with the rat muscle fibers and restored the ability of the fibers to remodel, whereas addition of either a fibroblast cell line or a transformed, non-fusing variant of C2C12 cells, or addition of conditioned medium from C2C12 cells, failed to do so. These results imply that myoblast fusion is responsible for triggering adult fiber remodeling in vitro. PMID- 2209462 TI - Neurogenic and antineurogenic effects from modifications at the Notch locus. AB - The best studied mutations at the Notch locus produce a neurogenic phenotype, with a massive overgrowth of the nervous system at the expense of epidermis. We report here that, in the development of the adult peripheral nervous system, the Abruptex alleles of Notch have the opposite phenotype, namely an underproduction of sensory organs or sensilla. This arises primarily not from an arrest of the lineages that produce sensilla, from the degeneration of sensillar cells, or from the transformation into neurons of cells that normally secrete the cuticular components of a sensillum (as can happen in Notch alleles). Rather, our evidence argues strongly that the sensillar mother cells never form. This implies that the Notch protein plays a role in the process that first generates a difference between sensillar mother cells and ordinary epidermal cells. The number of sensilla formed on the wing of flies carrying multiple doses of Notch+ is virtually the same as that of wild type, i.e. the Abruptex phenotype is not reproduced to any significant extent. This suggests that the single amino acid substitutions that occur in Abruptex mutants confer on the protein some functionally distinctive feature, possibly more powerful intermolecular binding or altered stability. PMID- 2209463 TI - Neurogenesis in the insect enteric nervous system: generation of premigratory neurons from an epithelial placode. AB - The enteric plexus (EP) is a major division of the enteric nervous system (ENS) in the moth Manduca sexta and contains a dispersed population of about 360 bipolar neurons, the EP cells. Previously we showed that embryonic EP cells achieve their mature distributions by extensive migration along the gut surface and then display position-specific phenotypes. We now demonstrate that the entire EP cell population is generated from an ectodermal placode that invaginates from the embryonic foregut. Individual EP cells become postmitotic just as they leave the epithelium, but their terminal differentiation is subsequently delayed until after their migratory dispersal. Clonal analysis by injection of lineage-tracing dyes has shown that the EP cell population is derived from a large number of placodal cells, each of which contributes a limited number of neurons to the ENS. Placodally derived clones produce neurons exclusively, while clones arising from cells adjacent to the placode are incorporated into the gut epithelium. These results indicate that neurogenesis in the insect ENS involves a developmental strategy that is distinct from that seen in the insect CNS and which resembles the generation of certain cell classes in the vertebrate nervous system. PMID- 2209464 TI - Detrimental effects of two active X chromosomes on early mouse development. AB - Matings between female mice carrying Searle's translocation, T(X;16)16H, and normal males give rise to chromosomally unbalanced zygotes with two complete sets of autosomes, one normal X chromosome and one X16 translocation chromosome (XnX16 embryos). Since X chromosome inactivation does not occur in these embryos, probably due to the lack of the inactivation center on X16, XnX16 embryos are functionally disomic for the proximal 63% of the X chromosome and trisomic for the distal segment of chromosome 16. Developmental abnormalities found in XnX16 embryos include: (1) growth retardation detected as early as stage 9, (2) continual loss of embryonic ectoderm cells either by death or by expulsion into the proamniotic cavity, (3) underdevelopment of the ectoplacental cone throughout the course of development, (4) very limited, if any, mesoderm formation, (5) failure in early organogenesis including the embryo, amnion, chorion and yolk sac. Death occurred at 10 days p.c. Since the combination of XO and trisomy 16 does not severely affect early mouse development, it is likely that regulatory mechanisms essential for early embryogenesis do not function correctly in XnX16 embryos due to activity of the extra X chromosome segment of X16. PMID- 2209465 TI - Expression of basic fibroblast growth factor in the nervous system of early avian embryos. AB - Basic fibroblast growth factor (bFGF) promotes the survival of a subpopulation of non-neuronal cells developing from trunk neural crest. It was therefore important to determine whether this factor is present in the nervous system at early developmental stages. Immunocytochemistry using specific polyclonal and monoclonal antibodies was combined with three highly sensitive assays: bFGF induced proliferation of bovine adrenal cortex-derived capillary endothelial cells (ACE), a radioimmunoassay for bFGF (RIA) and Western blot analysis. bFGF immunoreactivity was localized to the cytoplasm of neuroepithelial cells derived from embryonic day 2 (E2) quail neural tubes and cultured for one day in a chemically defined medium. Specific staining was observed in young sensory neurons in cultures of neural crest clusters as well as in a subpopulation of non neuronal cells. In cultured E7 dorsal root ganglia, immunostaining was confined to neuronal cell bodies and fibers. In situ, staining of spinal cord and ganglionic neurons appeared on E6 and increased in intensity towards E10. Various mesoderm-derived structures such as the limb buds, the mesenchyme dorsal to the neural tube, the vertebral muscles and cartilage showed specific staining patterns in addition to neural tissue. In agreement with the results of immunocytochemical studies, 1.4ng bFGF per mg protein was detected in spinal cord extracts by RIA as early as E3, its concentration increased to 8.0 ng mg-1 on E5 and then to a maximum of 18.0 ng mg-1 protein on E10, this was followed by a subsequent decrease in concentration in older embryos. On the other hand, high levels of bFGF were present in vertebral tissues from E10 onwards. Extracts of immunopositive tissues were subjected to heparin-Sepharose affinity chromatography and eluted in a stepwise salt gradient. Fractions that eluted from the columns at 2 M NaCl contained a bFGF-like protein as revealed by their ability to stimulate the proliferation of ACE cells and by Western blot analysis. These data demonstrate that bFGF is expressed during early nervous system development in both central and peripheral neurons. PMID- 2209466 TI - Disuse and passive stretch cause rapid alterations in expression of developmental and adult contractile protein genes in skeletal muscle. AB - Contractile proteins exist as a number of isoforms that show a developmental and tissue-specific pattern of expression. Using gene-specific cDNA probes, the expression of the sarcomeric myosin heavy chain (MHC) multi-gene family and of cardiac (foetal) alpha-actin was analysed in three different rat hindlimb muscles immobilised for 5 days in either the shortened or lengthened positions. For each of the MHC genes normally expressed in adult muscle (slow, IIA and IIB), the effect of disuse alone (immobilisation in the shortened position) upon expression was markedly different to that of passive stretch (immobilisation in the lengthened position) in each of the three muscles. However, the same adult sarcomeric myosin heavy chain gene can be affected in a different, or even opposite, manner by either disuse or passive stretch depending on the muscle in which it is being expressed. The fast IIB MHC gene, for example, exhibits a rapid induction in the slow postural soleus muscle, in response to disuse but no such induction occurs in the faster plantaris and gastrocnemius muscles. Furthermore, the induction of this gene in the soleus was prevented by passive stretch. The MHC gene, normally only expressed in embryonic skeletal muscle, showed a similar response in all three muscles and was reinduced in adult muscle in response to passive stretch but not by disuse alone. In contrast, the isoform of alpha-actin which is normally only present in significant quantities in embryonic skeletal muscle and which is reduced postnatally, is not reinduced by passive stretch but is reduced still further by immobilisation in the shortened position. PMID- 2209467 TI - Molecular analysis of the Mov 34 mutation: transcript disrupted by proviral integration in mice is conserved in Drosophila. AB - The Mov 34 mutation is a recessive embryonic lethal mutation caused by retroviral integration in the murine germline. This integration disrupts a transcription unit that appears to encode a novel protein. The Mov 34 proviral integration is located on mouse chromosome 8 and the human homolog of this gene has been mapped to chromosome region 16q23-q24. An evolutionarily conserved syntenic relationship exists between this region of human chromosome 16 and a region of mouse chromosome 8 that also contains oligosyndactyly (Os), another recessive lethal mutation. Genetic studies have ruled out Os as residing at the same locus as the Mov 34 integration. The Mov 34 transcript is conserved in evolution, and a Drosophila homolog appears to encode a protein with 62% amino acid identity to the murine protein. In situ hybridization to Drosophila polytene chromosomes localizes the Drosophila homolog to 60B,C on chromosome 2. Several Drosophila lethal mutations also map to this region. PMID- 2209469 TI - A study of meiosis in chimeric mouse fetal gonads. AB - The influence of somatic environment on the onset and progression of meiosis in fetal germ cells was studied in chimeric gonads produced in vitro by dissociation reaggregation experiments. Germ cells isolated from testes or ovaries of 11.5 13.5 days post coitum (dpc) CD-1 mouse embryos were loaded with the fluorescent supravital dye 5-6 carboxyfluorescein diacetate succinimyl ester (CFSE) and mixed with a cell suspension obtained by trypsin-EDTA treatment of gonads of various ages and of the same or opposite sex. Whereas 11.5 dpc donor germ cells appeared unable to survive in the chimeric gonads obtained, about 76% of the CFSE-labeled female germ cells obtained from 12.5 dpc donor embryos (premeiotic germ cells) found viable within host ovarian tissues showed a meiotic nucleus. In contrast, a smaller number (about 19%) were in meiosis in chimeric testes. None or very few of donor male germ cells entered meiosis in testes or ovarian host tissues. Aggregation of meiotic 13.5 dpc female germ cells with testis tissues from 13.5 to 14.5 dpc embryos resulted in inhibition of meiotic progression and pyknosis in most donor germ cells. These results support the existence of a meiosis preventing substance or a factor causing oocyte degeneration in the fetal mouse testis, but not of a meiosis-inducing substance in the fetal ovary. PMID- 2209468 TI - Colocalization of TGF-beta 1 and collagen I and III, fibronectin and glycosaminoglycans during lung branching morphogenesis. AB - The possible in vivo role of TGF-beta 1 in regulating various proteins of the extracellular matrix, including fibronectin, collagen I and III, and glycosaminoglycans, was examined by immunohistochemical methods during critical stages of lung morphogenesis in the 11- to 18-day-old mouse embryo. Sections of Bouin-fixed, paraffin-embedded whole embryos were exposed to polyclonal antibodies specific to synthetic peptides present in the precursor part of TGF beta 1 (pro-TGF-beta 1), in the processed TGF-beta 1 (antibody CC), collagen I and III, fibronectin, followed by the PAP or ABC technique to visualize the location of the antibody. GAG were stained with Alcian Blue 8GX. Our results indicate colocalization of TGF-beta 1 expression and that of matrix proteins in the developing lung when branching morphogenesis (cleft formation) and tissue stabilization occur. The presence of TGF-beta 1 at the epithelial-mesenchymal interfaces of stalks and clefts at a time when matrix proteins can first be visualized in these areas, suggests a direct participation of the growth factor in the development of the basic architecture of the lung. PMID- 2209470 TI - Distribution of insulin-like growth factor peptides in the developing chick embryo. AB - Growth factors are likely to be of major significance in developmental biology. Here, the distribution of insulin-like growth factor (IGF) peptides is described during development of the chick embryo. IGF was immunolocalised using a polyclonal antibody to human IGF I detected with a modified Vectastain ABC procedure. Under the conditions used, the antibody binds strongly to IGF I and weakly to IGF II; thus the distribution of IGF peptide, rather than the individual factors, is described. Muscle, peripheral nerve and the notochord were labelled whenever present. Muscle label was associated with the myotubes and neural labelling with neurons; Schwann cells were unlabelled. IGF distribution changed during differentiation of connective tissues. Regions of mesenchyme destined to form cartilage labelled weakly or not at all, and cartilage condensations were unlabelled. In the limb, chondrocytes became labelled once cartilage rudiments had formed; however, in later development, label was absent in zones of rounded and flattened chondrocytes and appeared strongly at the onset of hypertrophy. Early osteogenic mesenchyme was also unlabelled, although later bone cells were strongly stained. In the neural tube, label was associated with differentiating neuroblasts and cell bodies and with axons, especially in the developing dorsolateral tracts. These results show a possible correlation between IGF label and cell division in early mesenchyme; cartilage condensations, which have reduced mitotic indices, do not label. In other tissues, notably muscle and nerve but also later connective tissues, label is associated with differentiating, rather than dividing, cells. PMID- 2209471 TI - Three markers of adult non-myelin-forming Schwann cells, 217c(Ran-1), A5E3 and GFAP: development and regulation by neuron-Schwann cell interactions. AB - Immunohistochemical methods are used to investigate in detail the development and regulation of three proteins (217c(Ran-1), A5E3 and GFAP) specifically associated with adult non-myelin-forming Schwann cells in the rat sciatic nerve, from embryo day 15 to maturity. 217c(Ran-1), which is probably the NGF-receptor, and A5E3 are expressed by the majority of cells in the nerve at embryo day 15 and by essentially all cells at embryo day 18. GFAP first appears at embryo day 18; this is an intrinsically programmed developmental event which occurs in cultured Schwann cells even in the absence of serum. Postnatally, the expression of 217c(Ran-1), A5E3 and GFAP is suppressed in cells that form myelin but retained in non-myelin-forming Schwann cells. Mature myelin-forming cells nevertheless maintain the potential to express all three proteins but will only do so if removed from contact with myelinated axons. In neuron-free cultures Schwann cells express all three proteins. This work, together with our previous observations on N-CAM, shows that removal of a diverse set of surface proteins and a change in intermediate filament expression is one of the major consequences of axon to Schwann cell signalling during myelination in the rat sciatic nerve. Unlike myelin-forming cells, adult non-myelin-forming Schwann cells remain very similar to embryonic and newborn cells with respect to expression of surface proteins, in contrast to the previously established developmental changes that occur in their surface lipids. PMID- 2209472 TI - Skin blood flow changes, measured by laser Doppler flowmetry, in the first week after birth. AB - Changes in forehead skin blood flow were determined in 17 healthy, term newborns, using a fiberless diode laser Doppler flow meter (Diodopp). Measurements were carried out three times on each infant, at postnatal ages of 16.8 +/- 7.4 h, 58.9 +/- 6.2 h and 121.5 +/- 14.2 h (mean +/- S.D.), respectively. Skin blood flow, respiration, heart rate and skin temperature were recorded simultaneously, while the newborns were asleep. During the recordings, the behavioural state of the newborns was observed and environmental temperature and humidity were kept constant. Postocclusive hyperaemia of the skin blood flow was obtained by pressing the laser Doppler probe against the skull for 30 or 60 s. The following parameters changed significantly between the first and third measurements (t-test for paired samples): the basal skin blood flow during active and quiet sleep decreased, the average decrease being 29.4% (P = 0.002) and 25.9% (P = 0.01), respectively; skin blood flow during postocclusive hyperaemia also changed: the time taken to reach maximum hyperaemia increased from 17.3 to 22.7 s (P = 0.01), while the halftime recovery increased from 46.1 to 57.1 s (P = 0.02). The changes in skin blood flow between the first and second measurements and between the second and third measurements did not reach the level of statistical significance. PMID- 2209473 TI - Prenatal risk factors for cot death in very preterm and small for gestational age infants. AB - In a nationwide prospective survey on very preterm and very-low-birthweight infants in The Netherlands, the incidence of cot death in infants discharged alive was 15%. The postnatal age at death in these infants did not differ significantly from age at death in other cot death infants. Using a case-control design, possible risk factors associated with cot death were identified: lower maternal age at first pregnancy; maternal smoking during pregnancy; hypothermia of the infant immediately after birth; decreased number of white blood cells and thrombocytes in the infant on the first day of life. Intrauterine hypoxia is hypothesized as the entity common to these factors. PMID- 2209474 TI - Differential growth between the fetal brain and its infratentorial part. AB - From 298 normal fetuses, we established normative curves of the development of the brain in relation to gestational age and to body weight. Means and standard deviations were calculated. There exist good curvilinear relationships, expressed by polynomial models, between brain weight--body weight and brain weight- gestational age with a wider scatter in large fetuses. These results confirm literature data. Subsequently, fresh and fixed brain weights were analysed. In addition, the development of the infratentorial part of the brain was studied with the same methods and showed close relationship with age and total brain weight. The ratios: infratentorial weight/total brain weight, brain stem/total brain weight and cerebellum/total brain weight were expressed as percentages. After 20 weeks, the cerebellar growth rate was higher than that of the brain stem. PMID- 2209475 TI - Influence of elective cesarean section and breech delivery on neonatal neurological condition. AB - Fifty-three infants born after elective cesarean section (CS), and 28 infants born vaginally in breech presentation were compared with 45 full-term controls. A quantitative neurological assessment consisting of 31 items was performed on days 1, 2 and 5 after birth. A tonus score, an excitability score and the number of optimal responses were calculated. A follow-up examination was done at 6 months of age, with a standardized neurological and developmental examination. The results showed that infants born after elective CS in both vertex and breech presentation had significantly reduced number of optimal responses during the first five days after delivery, compared to controls. They were more hypotonic and less excitable than the control infants during the first 2 days. There were no significant differences in neurological results between infants born after CS with general or epidural anaesthesia. The infants born in vaginal breech presentation showed no differences neurologically as compared to the controls on the first day. On days 2 and 5, however, they were less excitable and showed a reduced number of optimal responses. There were few differences in neurological condition between the infants born after elective CS and the infants born vaginally in breech presentation. Growth, psychomotor development and neurological status at 6 months did not differ significantly between the three groups. Our findings indicate that infants born after elective CS and vaginal breech presentation have a delayed neurological adaptation during their first days of life. These differences did not affect the physical well-being of the infants, which showed normal growth, neurology and development at the follow-up at 6 months of age. PMID- 2209476 TI - The association between fetal body movements, eye movements and heart rate patterns in pregnancies between 25 and 30 weeks of gestation. AB - Fetal eye movements, fetal body movements and fetal heart rate patterns were studied in healthy fetuses between 25 and 30 weeks of gestation in 21 recordings with a mean recording time of 83.5 min. In contrast with the older fetus, prolonged periods of absence as well as presence of fetal eye or body movements were uncommon. Especially absence of body movements for more than 15 min is extremely rare at this age. These findings emphasize that for the interpretation of fetal biophysical tests, gestational age should be taken into account. A linkage was demonstrated between fetal eye movements and fetal heart rate pattern and between fetal body movements and fetal heart rate pattern, but not between fetal eye movements and fetal body movements. The existence of fetal behavioural states could not be demonstrated. PMID- 2209477 TI - [Alzheimer's disease and the zinc theory]. AB - In Alzheimer's disease, the Primum Movens is amyloid production on precapillaries: dysphoric angiopathy, and capillaries: senile plaques. Cerebral amyloid alone may be asymptomatic. Clinical symptoms of amnesia appear when amyloid induces neighbouring neuritic alterations: paired helical filaments and distant neuronal body lesions: neurofibrillary tangles. HYPOTHESIS: the amyloid induces zinc deficiency which produces the tangles. In Alzheimer's disease, cerebral zinc decreases particularly in the hippocampus. Without amyloid, neurofibrillary tangles are produced by metalotoxicity and therefore probably brain zinc displacement: by lead: encephalopatia saturnica, by calcium deficiency: Guam's encephalopathy, by aluminium, by blood-brain-barrier disturbances probably leading to an abnormal entry of metals in the brain (dementia pugilistica, viral encephalitides). Neurofibrillary tangles may be produced by deficiency of the following zinc enzymes: 1) those of DNA metabolism inducing abnormal DNA and therefore abnormal protein synthesis: paired helical filaments and neurofibrillary tangles; 2) of glutamate-dehydrogenase resulting in an excitotoxic increase of glutamate, which may produce neurofibrillary tangles, particularly in the hippocampus rich in glutamate pathways; 3) those of neuronal detoxication: superoxide-dismutase, carbonic anhydrase, lactate-dehydrogenase leading to neuronal toxicity particularly in the hippocampus normally rich in superoxide dismutase; 4) those of neurotransmitters metabolisms (opioid peptides, GABA, acetylcholine). Therapeutic implication: a non-toxic zinc complex crossing the Blood-Brain-Barrier should be useful. PMID- 2209478 TI - [Cure of amineptine dependence with clonidine?]. AB - Two patients with dependence to amineptine were treated with clonidine which is used in morphine withdrawals. After some days, the two patients stopped amineptine intake. The only way of action seems to be the potentialization of amineptine by clonidine, as probed in mice, or the increase of sensibilization of alpha 2 adrenoreceptors. PMID- 2209479 TI - [Transcerebral electrostimulation in hypnotic drug withdrawal]. AB - This preliminary study attempted to test the efficacy of electrosleep therapy on hypnotic drug withdrawal. Among 89 outpatients complaining of chronic insomnia and receiving a heavy hypnotic drug treatment, an efficient withdrawal associated with a marked improvement of self-reported sleep was observed in 78% of cases, especially when insomnia was not related to medical aetiologies or to major psychiatric disorders. These results suggest further controlled studies to determine the magnitude of the placebo component in the effect observed. PMID- 2209481 TI - [Ethics and clinical trials]. AB - Clinical research is indispensable for determining the safety and efficacy of drugs in human. It provides the scientific basis for rational drug usage. Methodology of clinical trials can raise some ethical issues. As an example the use of a placebo is described in this paper. Generally the ethical issues may be solved by the adequate information of every individual assigned to clinical investigation in agreement with the Declaration of Helsinki and the Huriet law. This information must be approved by an ethical committee. Finally an information about the general provisions of clinical trials must be destined to the general public. PMID- 2209480 TI - [Erythrocyte membrane transport of tyrosine and tryptophan and plasma level of MHPG in depressive disorders]. AB - Both plasma MHPG level and red blood cell membrane transports (TM) of L-tyrosine (L-TYR) and L-tryptophan (L-TRY) were evaluated in 29 depressed patients and compared to 16 control subjects. On the basis of MHPG plasmatic levels, we were able to define two subgroups in the depressed population showing a biological homogeneity: in the first one, both MHPG level and TYR TM decreased, while in the second one neither of these indices were disturbed. These biological features were not related to the nosographic subgroups. Bipolar depressed subjects showed a decrease in both MHPG and TYR TM; unipolar depressed subjects exhibited a decrease in both MHPG and TYR TM associated to an increase in TRY TM, whereas no change was found in dysthymic disorders. The time course of MHPG and MT were desynchronized if followed during the antidepressant treatment. At day 7, MHPG level increased significantly, while clinical improvement showed a normalisation of MHPG and TYR TM. PMID- 2209482 TI - [Informed consent of patients in psychiatry. Consequences in biomedical research]. AB - After the Huriet law (December 20th 1988) a free, informed and explicit consent procedure has become compulsory in biomedical research. This obligation is particularly uneasy with mental patients. Stricto sensu it excludes from research all psychotic patients unable to become "informed" and to "consent" to something. Moreover age, understanding, the quantity of informations, the personality of investigators and above all patients' suggestibility may be biases when recruiting subjects willing to participate in a trial. It is only after marketing that a thorough knowledge of the scope of a new drug will be established in terms of efficacy. Furthermore, patients informed about the possible ingestion of a placebo may become less responsive to the placebo as well as to the active drug. In a double-blind trial the physician will be unable to explain the effects experienced during the treatment period. The Huriet law should be adjusted taking into account the specificity of the field of psychiatry and being aware of the treatment and investigational problems within the framework of psychiatric emergencies. PMID- 2209483 TI - [Ethics and clinical drug trials]. AB - During the last decade, biomedical ethics has known a rapid development. Research in man, including clinical drug trials, must now take into account ethical and legal requirements. The concept of the inviolability of the human person constitutes the basic tenet of biomedical ethics. Four main principles ensue: the principles of autonomy, of nonmaleficience, of beneficience and of justice. Some rules derive from them, for instance veracity, confidentiality, fidelity and respect of intimacy with regard to the subject of an experiment. From a practical standpoint, the design of a clinical trial must be scientifically sound, otherwise it cannot be ethical. An informed consent must be obtained, in written form, from the subject in a clinical trial and he must be aware of his right to withdraw from it at any moment. Moreover, the clinical trial must be monitored throughout its duration with respect to ethics. An ethics of the methodology of clinical trials must therefore exist. Ethics in research should be a way of thinking and behaving, inherent to the research training. The researcher should be keenly conscious of the ethical requirements involved in his work, if he wishes to avoid eventual external interventions. PMID- 2209484 TI - [Current clinical aspects of obsessive disorders]. AB - The clinical approach to obsessional troubles has barely evolved since the symptoms were first referenced throughout the 19th century. Recent developments in active therapeutics have led to studies on large series of patients. Thus, the various clinical and evolutive aspects, the borderline forms and associated pathologies (other anxiety troubles, depression and mental anorexy) have been delineated. PMID- 2209485 TI - [Standardized evaluation of obsessive phenomena in patients in general medicine. Prevalence and correlations]. AB - Clinical experience in general hospital psychiatry and literature reviews supported the conjecture that psychopathological disturbances are frequent among medical patients. Wide discrepancies of prevalence data reported by different authors, however, suggested the importance of undertaking screening studies with standardized methods of assessment. Our initial studies in oncological patients confirmed the hypothesis, but also documented obsessive phenomena, assessed with Present State Examination (PSE) criteria, in more than one third of patients diagnosed of depression Consecutive studies in different medical samples have replicated those preliminary findings in the last one, close to one quarter of first day consecutive patients seen in an internal medicine out-patient clinic, and more than three quarters of the ones diagnosed of either anxiety or depression with Research Diagnostic Criteria, had obsessive symptoms as defined by the Clinical Interview Schedule (CIS). Obsessive symptoms, however, have also been observed in individuals considered to be "non-cases" and tend to follow a "continuum" distribution, rather than a categorical one They tend to be more frequent in cases diagnosed as neurotic or reactive, rather than in the endogenous ones and to correlate with neuroticism measured by the EPQ-A. Particularly among out-patients, where the psychopathology seemed to be related to the absence of demonstrable somatic illness and probably to the presence of social distress, the hypothesis could be advanced that obsessive symptoms, among other psychopathological phenomena, are quantitative reactions to environmental situations in predisposed individuals. Nevertheless, in samples such as the endocrine in-patients, correlations have also been demonstrated between obsessive or other psychopathological symptoms and biological deviations such as hormonal levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2209486 TI - [Psychoanalytic and clinical prospects of obsessive disorders]. AB - Is there a possible meeting-point between the psychoanalytical views of obsessive neurosis and the purely descriptive approach to symptoms, i.e. the biological, cognitive or behavioral explanations of symptoms? Obviously, it is impossible to dream of a general consensus since the processes concerned by the various therapeutic methods are not alike. What would be, for a behavior specialist, the value of discussing the reality of the primitive scene so dear to psychoanalysts? What would be, for a psychoanalyst, the value of discussing the comparative merits of the several conditioning methods? A confrontation is possible only in those fields that are common to all the parties. In this report two of these have been selected: the debate on the genesis of obsessive disorders (are they psychogenetic or organogenetic?) and the clinical study. Today's psychoanalysis discuss the first subject only sparingly, but Freud has given it much thought and it is surprising to find out to what extent his thought is in agreement with the current trends. As to the second subject, there is obviously a possibility for confrontation of the various views, since, regarding obsessive disorders, psychoanalysis provides a psychopathological model suitable for clinical practice and allowing the synthesis of the various manifestations to be made and the behavioral dynamics to be understood. I shall try to show how this model can be used profitably, even if one is ignorant of, or not familiar with, psychoanalytical metapsychology. PMID- 2209487 TI - [Epidemiology of obsessive-compulsive disorder in children and adolescents]. AB - Although obsessive-compulsive disorders are rarely found in young subjects seen in infantile psychiatry, anamnestic studies have shown that more than one third of obsessive patients seen at adult age agree that the onset of their disorder dates back to when they were under 15 years of age. The first direct epidemiological study on the prevalence of obsessive-compulsive disorder during adolescence was recently conducted in a New Jersey county, USA. Over 5,500 high school teenagers were asked to fill in a questionnaire dealing with different aspects of mental pathology and 356 of them were selected, on the basis of their answers, to be included in further clinical examinations. Thus, the current prevalence rate of obsessive-compulsive disorder was found to be 1 (+/- 0.5)% of the general adolescent population, and the lifetime prevalence rate, 1.9 (+/- 0.7)%. These results are close to the rates of prevalence observed in the U.S. general adult population during the same period. The obsessive-compulsive cases detected in this investigation showed the same characteristics as the clinical cases usually described, except for the absence of male predominance generally observed in consulting patients; 75% of obsessive patients also presented other associated psychopathological disorders, most often major depression, overanxious disorder and/or bulimia, but only 20% of them had already consulted mental health professionals. This study shows that obsessive-compulsive disorder during adolescence is more frequent than expected, but often remains undiagnosed and untreated. PMID- 2209488 TI - [Obsessive-compulsive disorders in adolescents]. AB - The research recently conducted and ongoing in adolescent obsessive-compulsive disorder indicates that the clinical signs and symptoms are indistinguishable from those seen in adults. Comorbidity appears to follow the same trends in adolescents and adults, with anxiety and affective symptomatology predominating. Contrary to expectation, Gilles de la Tourette disorder does not appear either as a concurrent syndrome, or as an eventual outcome in obsessive-compulsive adolescents. Males are greatly over-represented among adolescents with an early childhood onset. The neurological and neuropsychological findings are the only ones that appear to distinguish the adolescent and adult obsessive-compulsive patients. The findings point to frequent neurological abnormalities in adolescents with obsessive-compulsive disorder. The natural history over the short-term seems to be negatively affected by severity. The clinical efficacy of clomipramine and the failure of another tricyclic antidepressant parallels the therapeutic experience reported in adult patients. The presence of depression is unrelated to the efficacy of clomipramine. The neuropsychological and neurological abnormalities, together with the data from the longitudinal and treatment studies, strongly suggest that obsessive-compulsive disorder in adolescents is not a variant of the overall group of anxiety disorders. PMID- 2209489 TI - Gilles de La Tourette's syndrome and some forms of obsessive-compulsive disorder may share a common genetic diathesis. AB - Family aggregation and twin studies suggest that Gilles de La Tourette's syndrome (TS) and some forms of obsessive-compulsive disorder (OCD) are etiologically related. Neuroanatomically, the structures of the basal ganglia, thalamus and cortex have also been implicated in both TS and OCD suggesting a common neural substrate for these disorders. Neurochemical and neuropharmacological studies have provided less compelling data concerning this heuristically important association. Clinical studies have largely focused on the role of the nigrostriatal, mesolimbic and mesocortical dopaminergic systems in the pathophysiology of TS. In the case of OCD, serotoninergic systems originating in the raphe nuclei and projecting rostrally, have received considerable attention. Recent neuropathological studies of TS have implicated the endogenous opioid peptide, dynorphin, in the pathophysiology of TS. Animal studies have shown that dynorphin can modulate both dopaminergic and serotonergic systems. We have undertaken a cerebrospinal fluid (CSF) study to determine if abnormalities in dynorphin A concentration can be observed in drug-free TS and OCD patients. Preliminary results from this study suggest: 1) that TS patients have an elevated level of CSF dynorphin A (1-8) compared to normal controls; 2) that their level of CSF dynorphin is correlated with the severity of their OCD symptoms; 3) that some, but not all, OCD patients also have high levels of this neuropeptide in their CSF. PMID- 2209490 TI - [The obsessive-compulsive syndrome: reflection of fronto-caudate dysregulation of the left hemisphere?]. AB - Neuropsychological studies of the obsessional syndrome reveal bilateral frontal dysfunction. Early onset is characteristic of males, who have a more chronic course than females, and who are more often non-dextral. Hypermetabolic activity of the frontal and caudate, bilaterally, is found in most PET investigations, although one report is of relative hypofrontality and global cortical hypometabolism for absolute values. Given the frequency with which basal ganglia disease leads to obsessive-compulsive phenomena (Cf Sydenham's Chorea, Gilles de La Tourette) and frontal lobe inertia, a perturbation of frontal-caudate regulatory motor and ideational sub-systems in the obsessional syndrome appears probable. Bilateral caudate atrophy on CT scan has been reported. Further, EP investigations, both somatosensory and auditory, implicate the left hemisphere in obsessions; together with reduced P300 latencies and during imaginal flooding there is increased left (frontal) hemisphere flow (rCBF). Single case studies document the relationship of obsessions to left frontal-left caudate unilateral pathology. It is suggested that lateralized dysregulation of the left fronto caudate network is the major cerebral determinant of obsessive-compulsive states. PMID- 2209491 TI - Pharmacotherapy of obsessive-compulsive disorder. AB - Due to its chronic and refractory nature, a wide variety of medications have been used in the treatment of obsessive-compulsive disorder (OCD). The most promising development has been with the tricyclic antidepressant clomipramine (Anafranil). More recently, a series of well controlled double blind studies have documented that clomipramine is more effective than placebo in reducing OCD symptoms. In a review of all 7 CMI studies with a total of 106 patients, two-thirds were found to be significantly improved on blind ratings (Insel and Zohar, 1988). Controlled studies also suggest clomipramine is more effective than other antidepressants for the treatment of OCD. Oral m-CPP (m-chlorophenyl piperazine), a selective 5HT agonist, has been found to increase obsessions in OCD patients when given acutely (Zohar, 1987; Hollander, 1988). This effect has been shown to decrease after chronic treatment with clomipramine (Zohar et al., 1988) or fluoxetine (Hollander et al., unpublished observations), suggesting that chronic treatment may correct serotonin dysregulation. PMID- 2209493 TI - [Behavior psychotherapy in obsessive-compulsive disorders]. AB - Although their problem is often as disabling as in chronic schizophrenia, most cases of obsessive-compulsive disorder have become eminently treatable by the behavioural approach of live exposure with response prevention. Treatment takes from 1 to 6 months depending on the severity of the problem, and may need an overall mean therapist time of +/- 8 hours time per patient. Most psychiatrists can learn to apply the treatment quite quickly, and most patients can be treated on an outpatient basis. About 25% of patients refuse or do not complete behavioural treatment. Improvement has endured over the 5-year follow-ups available. Occasional cases need brief booster period during followup. In exposure treatment the sufferer is persuaded to come into prolonged contact with discomfiting cues that bring on the rituals, without ritualising, so that the ensuing anxiety and urge to ritualise can subside to the point of habituation. The contact should be for at least an hour daily, and should gradually involve all ritual-evoking cues. The patient should record all exposure tasks done in a daily self-exposure diary. The therapist does not need to do the exposure with the patient, his role being to educate the patient in what to do and to monitor and praise progress. Therapist-accompanied exposure is largely redundant. Where family members are involved in the rituals they need to be coopted, with the patient's agreement, as exposure cotherapists and taught in role rehearsal with the patient to withhold requests for reassurance. Antidepressant drugs are a useful adjuvant to exposure therapy when the patient's obsessive-compulsive problem is complicated by dysphoria. PMID- 2209492 TI - [Biological treatments in obsessive-compulsive disorder]. AB - Obsessive-compulsive disorder (OCD) is emerging very clearly as a serotonin specific illness. The evidence for this comes from a variety of clinical sources. Firstly the efficacy of 5-HT uptake inhibitors, especially clomipramine, is consistent and strong. Secondly clomipramine has not merely been found to be effective against placebo in 9 placebo controlled studies, it is also found to be more effective in some studies than reference tricyclic antidepressants and monoamine oxidase inhibitors. In other studies tricyclic antidepressants do not appear to be better than placebo. The lack of efficacy of general antidepressants, neuroleptics and benzodiazepines supports the specificity of the serotonin effect. Thirdly the evidence of the efficacy of clomipramine in OCD without concomitant depression reported by Montgomery 1980 and supported by other studies suggests that 5-HT uptake inhibitors have a specifically anti-obsessional effect. The lack of response of depressive symptoms in OCD to other antidepressants suggests that these depressive symptoms are integral to OCD and will only respond when the OCD is treated. Many of the studies found efficacy for 5-HT uptake inhibitors compared with placebo despite both groups being treated with concomitant behaviour therapy. This argues either for behaviour therapy being relatively ineffective or for there being a synergistic effect with the 5 HT uptake inhibitor which is more likely. Results from studies with selective serotonergic probes with a worsening of OCD symptoms in response to the 5-HT1A agonist, m-chlorophenyl piperazine, add support to the serotonergic hypothesis of OCD but further investigation is needed. PMID- 2209494 TI - [Cognitive therapy in obsessive-compulsive disorders]. AB - Cognitive approach is presented both at a theoretical and clinical level. It enlarges and enriches the classical behavioral approach of obsessive-compulsive disorders. To date, controlled studies are too few to fully assert its value. Further investigations are justified to ascertain whether cognitive therapy has a value as such, or enhances the effects of more classical pharmacological and/or behavioral treatments. PMID- 2209495 TI - [Psychotherapy in patients with obsessive-compulsive disorder]. AB - The present paper is a study of the role of psychotherapy in the treatment of obsessive-compulsive disorders (OCD). It also includes an attempt to integrate several paradigms in order to obtain the best possible approach in helping each patient on an individual basis. The aim of this psychotherapy may limit itself to simple verifications in the pharmacotherapeutic follow-up, or it may be as ambitious as an attempt to modify the character structure of the individual. In the process of the latter case, one expects the defensive aim of symptoms to be no longer relevant, insofar as the patient successfully solves the conflicts that caused the symptoms. We can only use tags or labels to bear witness of the efficiency of such ambitious use of psychotherapy, and even these tags or labels seem to be concerned with compulsive personality rather than with OCD proper. At each end of the range of aims (encouraging the follow-up of pharmacotherapeutic or behavioral treatments vs character modification), the therapist is inevitably confronted with a multitude of features frequently present in the obsessive patient. Because it is a disorder which invades and influences the patient's feelings, thoughts, behavior and relationships with other people, the obsessive patient's mind is a constant prey to special problems at every meeting with his therapist, whether they be related to the administration of drugs or to a behavioral therapy regime. Obviously, such problems will multiply if one initiates systematic psychotherapy in such patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2209496 TI - Injection therapy of bleeding peptic ulcer. A prospective, randomized trial using epinephrine and thrombin. AB - A prospective randomized trial involving 64 patients with bleeding peptic ulcers was performed to assess the efficacy of two modalities of injection therapy. The inclusion criterion was the presence of active bleeding or a visible vessel at emergency endoscopy. Thirty-two patients were treated with epinephrine (Group A) and 32 with epinephrine plus thrombin (Group B). Permanent hemostasis was achieved in 81.3% Group A, and 84.4% Group B patients, and therapy failures occurred in 18.6% and 15.6%, respectively. Mortality was nil in both groups. There were no differences in the requirement for emergency surgery, or in the number of transfusions in the two groups. A second elective endoscopy was performed in 49 patients between the 3rd and the 5th day after admission, proceeding to a second injection therapy if a visible vessel was still seen. There were no failures among re-injected patients. With one exception, none of the failures occurred in patients in whom a second endoscopy was done. Our results suggest that injection therapy, which is a simple technique, should be considered as the initial treatment of choice in bleeding peptic ulcer. The addition of thrombin to epinephrine does not improve the results of the method. An early second endoscopy and local therapy if a visible vessel is still present, may further improve the results. PMID- 2209497 TI - Effect of N-butylscopolamine on sphincter of Oddi motility in patients during routine ERCP--a manometric study. AB - N-butylscopolamine is a generally accepted drug for the suppression of gut motility. Although it is used during routine ERCP, only few systematic studies have been carried out in patients to investigate its action on sphincter of Oddi motility. In the present study the effect of N-butylscopolamine on the motility of the sphincter of Oddi region has been evaluated in 17 patients undergoing routine diagnostic ERCP. The pressure parameters of these patients were compared with "normal values" obtained in 23 volunteers. A dose of 40 mg of N butylscopolamine bromide (Buscopan) i.v. significantly reduced the contraction frequency of the sphincter of Oddi from 5.4 +/- 1.2/min to 1.0 +/- 1.4/min (p less than 0.001), the contraction amplitude from 106.3 +/- 27.8 mmHg to 55.2 +/- 23.5 (p less than 0.01) mmHg, and the basal sphincter of Oddi pressure from 13.9 +/- 3.0 mmHg to 11.0 +/- 3.5 mmHg (p less than 0.05), but had no effect on the pressure gradient between the common bile duct and the duodenum. These results clearly demonstrate that N-butylscopolamine inhibits contractions of the sphincter of Oddi, and may thus facilitate the intubation of the papilla. PMID- 2209498 TI - Antibiotic prophylaxis of infectious complications with endoscopic retrograde cholangiopancreatography. A randomized controlled study. AB - Biliary sepsis represents a major percentage of fatal complications after endoscopic retrograde cholangiopancreatography. We performed a randomized controlled study to investigate the value of antibiotic prophylaxis, and to assess the frequency and source of infectious complications associated with ERCP. Ninety-six patients who underwent 100 endoscopic retrograde cholangiopancreatographies were included in the study. Half of the patients received antibiotic prophylaxis (Cefotaxime 2 g i.v. 15 min before the procedure). Bacteremia was detected in 2% of the patients receiving antibiotic prophylaxis, as compared with 16% (p less than 0.02) in the control group. In order to determine the source of bacteremia, bile samples and irrigation fluid from the suction channel of the endo-scope were obtained for bacteriological evaluation. Several lines of evidence suggested that bacteremia associated with ERCP was essentially caused by mucosal lesions of the oropharynx. Bacteremia was asymptomatic, with the exception of two patients who subsequently developed fever, but recovered rapidly under antibiotic therapy. The frequency of cholangitis following ERCP was not significantly reduced by antibiotic prophylaxis (4% vs. 2%). Recommendations for antibiotic prophylaxis are discussed. PMID- 2209500 TI - Retroperitoneal perforation during ERCP and endoscopic sphincterotomy: causes, clinical features and management. AB - Eleven patients with retroperitoneal perforation complicating endoscopic management of bile duct obstruction were seen over a seven-year period. In nine patients endoscopic sphincterotomy or pre-cut papillotomy had been performed, but in two who had not undergone sphincterotomy perforation occurred because of the penetration of a guidewire during attempts to negotiate a malignant bile duct stricture. Eight out of eleven patients remained asymptomatic, and all recovered with conservative management. Asymptomatic retroperitoneal perforation can complicate therapeutic ERCP even when sphincterotomy is not performed, but conservative management is usually effective if the complications is recognized immediately. PMID- 2209499 TI - Golytely preparation for colonoscopy: 1.5 liters is enough for outpatients. AB - In a prospective double-blind study of the effectiveness and patient acceptance of Golytely whole-gut preparation for colonoscopy, 50 consecutive patients were randomly allocated to drink either 1.5 l (Group I) or 3 l (Group II). The patients had some slight dietary restrictions, and received mild laxatives on the preceding day. The cleansing result did not differ significantly in the two groups. The result was assessed as "good" in 76% of cases in Group I (95% confidence limits 55-91%) and in 83% of cases in Group II (95% confidence limits 63-95%). In half of the remaining cases in both groups the result was "acceptable" and in the other half "poor". Patient acceptance did not differ significantly in the two groups. After completion of the randomized study, oral cleansing with 1.5 l Golytely has been our daily routine. In 42 patients so treated quality of cleansing was good in 81% (95% confidence limits 66-91%), acceptable in 12%, and poor in 7%. PMID- 2209502 TI - Acute gallstone pancreatitis and endoscopic therapy. PMID- 2209501 TI - ESWL and gallstone dissolution with MTBE via a naso-vesicular catheter. AB - Endoscopic placement of a naso-vesicular catheter was successful in 90% (45/50) of patients with cholecystolithiasis. The first 7 patients were treated by MTBE dissolution alone. Dissolution was discontinued after a maximum of 14 days, as only two patients were rendered stone free. In one patient, 3 tiny pigment stones were sucked out through the catheter, and in another inoperable patient a pigtail endoprosthesis was finally inserted into the gallbladder. In the remaining 36 patients, combined ESWL and MTBE dissolution therapy was carried out. Treatment was broken off by one patient after one week, and interrupted in another due to catheter dislodgement. After an average of 10 days with 1-9 ESWL sessions (average: 3) complete stone clearance was achieved in 60% (20/34) of patients. Fourteen of the patients who completed treatment, and the one with catheter dislodgement still have sludge in the gallbladder, which is being treated with oral bile acids. The procedure-related complication rate was 10% (3 pancreatitis, 1 cystic duct perforation and 1 guidewire impaction). The mortality rate was zero. There was no evident complication due to either ESWL or MTBE dissolution. PMID- 2209503 TI - Acute primary HIV-esophagitis. AB - We report on a case of acute primary HIV-esophagitis in a 29-year-old man, who presented with fever, diarrhea, odynophagia and a skin rash. Endoscopy of the esophagus revealed multiple small shallow ulcerations. HIV-1 p24 antigen could only be shown in the blood on the day of admission to hospital, 7 days after the acute onset on the disease. Seroconversion for HIV-1 antibodies took place 2 days after the onset. PMID- 2209505 TI - Cannulation of the cystic duct and gallbladder (Endoscopy vol. 21, Sept. 1989, pp. 223-224) PMID- 2209504 TI - Collagenous gastroduodenitis on collagenous colitis. AB - We report on a case of collagenous gastroduodenitis with concomitant collagenous colitis in a 75-year-old woman with watery diarrhea of approximately six months' standing. The step biopsy material obtained from the colon revealed continuous collagenous colitis with thickening of the basal membrane to 30 microns. The biopsies taken from the stomach and duodenum also revealed a band-like deposition of collagen in the duodenum (bulb and proximal portion of the descending portion) along the basal membrane of the lining epithelium, associated with partial atrophy of the villi. In the stomach, this band of collagen was located, parallel to the mucosal surface, at the level of the floor of the foveolae. PMID- 2209506 TI - A large Brunner's gland adenoma removed by endoscopic polypectomy. PMID- 2209508 TI - Allergic reaction to contrast medium after endoscopic retrograde pancreatography. PMID- 2209507 TI - Endoscopic treatment of a duodeno-cutaneous fistula with fibrin tissue sealant (TISSUCOL) PMID- 2209509 TI - Enema preparation for proctosigmoidoscopy does not cause mucosal changes. PMID- 2209510 TI - Endoscopic treatment of bleeding peptic ulcers. Good in every situation? PMID- 2209511 TI - Galvanotaxis of human granulocytes: electric field jump studies. AB - The static and dynamic responses of human granulocytes to an electric field were investigated. The trajectories of the cells were determined from digitized pictures (phase contrast). The basic results are: (i) The track velocity is a constant as shown by means of the velocity autocorrelation function. (ii) The chemokinetic signal transduction/response mechanism is described in analogy to enzyme kinetics. The model predicts a single gaussian for the track velocity distribution density as measured. (iii) The mean drift velocity induced by an electric field, is the product of the mean track velocity and the polar order parameter. (iv) The galvanotactic dose-response curve was determined and described by using a generating function. This function is linear in E for E less than EO = 0.78 V/mm with a galvanotaxis coefficient KG of (-0.22 V/mm)-1 at 2.5 mM Ca++. For E greater than EO the galvanotactic response is diminished. This inhibition is described by a second term in the generating function (-KG.KI(E EO)) with an inhibition coefficient KI of 3.5 (v) The characteristic time involved in directed movement is a function of the applied electric field strength: about 30 s at low field strengths and below 10 s at high field strengths. The characteristic time is 32.4 s if the cells have to make a large change in direction of movement even at large field strength (E-jump). (vi) The lag-time between signal recognition and cellular response was 8.3 s. (vii) The galvanotactic response is Ca++ dependent. The granulocytes move towards the anode at 2.5 mM Ca++ towards the cathode at 0.1 mM Ca++. (viii) The directed movement of granulocytes can be described by a proportional-integral controller. PMID- 2209512 TI - Nutrients excreted in ileostomy effluents after consumption of mixed diets with beans or potatoes. I. Minerals, protein, fat and energy. AB - The small intestinal excretion of protein, fat, energy, magnesium, calcium, iron and zinc from two isocaloric diets including either instant bean flakes (174 g/d) or potato flakes (102 g/d) was studied in seven ileostomy subjects. Out of the variable part of the diet all starch and dietary fibre, and about half of the energy was provided from bean flakes or potato flakes, respectively. The small variation in ileostomy excretion between two consecutive days, after one adaptation day, suggests that ileostomy studies can be performed with reasonable precision in 2 days. During the 2-day potato period average daily excretions of gross energy and protein were 236 kcal (988 kJ; 11 per cent of intake) and 13 g (12 per cent), respectively. The excretions were significantly (P less than 0.001) higher during the bean period, 378 kcal (1582 kJ; 16 per cent) and 17 g (15 per cent). Fat intake and excretion were not different. After making allowance for dietary fibre, the apparent nutrient energy digestibilities were over 90 per cent, with only 43 kcal (180 kJ; 2 per cent) difference between the two periods. Apparent absorption of magnesium was lower during the bean period, 7 per cent compared to 25 per cent (P less than 0.02). The study has thus shown that only slightly less apparent small intestinal absorption occurs from a diet with bean flakes compared to potato flakes, so the nutritional consequences of beans on other nutrients seem to be small. PMID- 2209514 TI - Dietary intake and observed activity of stunted and non-stunted children in Kingston, Jamaica. Part II: Observed activity. AB - It is generally believed that activity levels are reduced in poorly nourished children. This may conserve energy, but may have a detrimental effect on mental development. However there are few data which support this hypothesis. No previous studies were found which looked at the activity levels of stunted children. In this study we modified the time and motion observation methods of Torun (1984) by using recording periods of 1 instead of 10 min. This significantly reduced the estimated time spent by young children in moderate and vigorous activities. Four hours of observing young children while they were awake, using the modified method, produced highly reliable data. The activity levels of a subsample of children described in part I were observed. The children were aged 12-24 months and were observed for 4 h on 2 d. Seventy-eight stunted children (height less than -2 SD of median, NCHS) were compared with 26 non stunted children (height greater than -1 SD). The stunted children were significantly less active than the non-stunted children, although the difference in activity rating was small (3.4 per cent). They spent more time in light activities (P less than 0.001) and less time in moderate or vigorous activities (P less than 0.01). Both groups slept a similar amount. Using Torun's values for the energy cost of activities it appears unlikely that the reduced activity would conserve energy to a great extent, but it may still be of biological importance, since it is comparable to the energy cost of growth at this age. Activity levels increased with age but were not significantly related to weight for height.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2209513 TI - Gastric emptying in infants with or without gastro-oesophageal reflux according to the type of milk. AB - The present study was designed to determine the effects of milk composition and the influence of gastro-oesophageal reflux (GOR) on gastric emptying. Cineoesogastrocintigraphy (COGS) was performed in 201 infants between 0-1 year of age in order to detect GOR, and provided a means of estimation of the gastric emptying (GE). Ninety infants appeared free from GOR and constituted the control group; 111 had GOR. There infants were fed human milk or various standard formulae. In addition, 20 infants fed a whey-hydrolysate formula were tested. An appropriate volume of milk was marked with sulfur-colloid Tc (200 microcuries). Measurements of gastric radioactivity were made 30 min and 120 min after ingestion. For the whole population, the infants with GOR had slightly more rapid GE after 30 min (P less than 0.05), but, for the same type of milk, there was no significant difference between GOR and controls. GE did not differ with age or sex, but differed mainly according to the type of milk. In the control group, gastric residual content (GRC) at 120 min was 18 +/- 11 per cent with human milk (n = 7), 16 +/- 21 per cent with whey-hydrolysate formula (n = 8), 25 +/- 17 per cent with acidified formula (n = 13), 26 +/- 19 per cent with whey-predominant formula (n = 22), 39 +/- 17 per cent with casein-predominant formulae (n = 20), 47 +/- 19 per cent with follow-up formulae (n = 16) and 55 +/- 19 per cent with cow's milk (n = 12).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2209515 TI - Diet and alcohol in liver cirrhosis: a case-control study. AB - A retrospective case-control study on alcohol and dietary habits was conducted over 3 years in a Gastroenterology Department on 152 male patients with liver cirrhosis. The study also included 304 hospital controls, selected within the same age range (32-83 years). Alcohol consumption and dietary habits were assessed from a standardized questionnaire by a highly trained dietician. The variations of the relative risk (RR) of liver cirrhosis as a function of the estimated mean daily intakes of alcohol, fats, carbohydrates and proteins were studied using stratified conditional logistic regression models. Obviously the relative risk of liver cirrhosis was found to be strongly and positively correlated with alcohol consumption but, in addition, this study has been able to show a significant and positive association with the mean daily fat intake and negative associations with the mean daily carbohydrate and protein intakes. Whereas in the control group, the calorie percentage from fats was 33.8 (87.11 g/d), it was 39.6 in the cirrhotic group (102.1 g/d). These findings indicate that in addition to alcohol consumption, dietary habits and in particular, high mean daily fat intake, should be considered. PMID- 2209516 TI - Pythiosis. PMID- 2209517 TI - Culicoides hypersensitivity. PMID- 2209519 TI - Naloxone-induced abdominal distress in the horse. AB - Endogenous opioid peptides have been implicated in the regulation of pain perception, behaviour, gastrointestinal activity and other physiological responses. However, the functional role of these peptides in the horse has yet to be elucidated. The opioid antagonist, naloxone, is often administered to infer endogenous opioid effects. In the present study, naloxone (0.75 mg/kg bodyweight) was administered to eight Thoroughbred racehorses and a number of behavioural and autonomic responses were measured. Naloxone produced rapid onset diarrhoea, restlessness, abdominal checking, tachycardia, tachypnoea, paradoxical yawning and diaphoresis. These responses described an acute abdominal distress syndrome similar to spasmodic colic. Results from this study suggest that, in the horse, endogenous opioids: 1) influence behaviour, 2) modify intestinal activity and sensation, and 3) if perturbed, may be involved in pathophysiology of colic. PMID- 2209518 TI - Specific immunotherapy in the treatment of Culicoides hypersensitive horses: a double-blind study. AB - Fourteen privately owned horses completed a six month, controlled, double-blind trial to assess the efficacy of immunotherapy using an aqueous extract of whole, unfed Culicoides variipennis in the treatment of Culicoides hypersensitivity. Selected horses had a history of a seasonal, pruritic dermatitis, clinical signs and distribution compatible with Culicoides hypersensitivity, failed to improve in response to ivermectin therapy, and reacted to several dilutions of Culicoides extracts without significant reactivity to other possible allergens including insects, moulds and feeds. One horse from the control group (n = 8) and one from the test group (n = 6) improved. Statistically, there was no significant difference between horses on Culicoides antigen and control horses. In each group, four owners thought that their horses had improved. PMID- 2209520 TI - The excretion of theobromine in Thoroughbred racehorses after feeding compounded cubes containing cocoa husk--establishment of a threshold value in horse urine. AB - Thoroughbred geldings were fed racehorse cubes containing a predetermined concentration of theobromine in the form of cocoa husk. They were offered 7 kg of cubes per day, divided between morning and evening feed, and food consumption was monitored. Urinary concentrations of theobromine were determined following the consumption of cubes containing 11.5, 6.6, 2.0 and 1.2 mg per kg of theobromine, to verify whether or not such concentrations would produce positive urine tests. Pre-dose urine samples were collected to verify the absence of theobromine before each experiment. It became apparent from the results of the first three administrations that the limit of detection of theobromine, using such procedures, would be reached at a feed level of about 1 mg per kg theobromine. Therefore the final administration, using cubes containing 1.2 mg per kg theobromine, was singled out for additional analytical work and quantitative procedures were developed to measure urinary concentrations of theobromine. It was anticipated that the results would form a basis for discussions relating to the establishment of a threshold value for theobromine in horse urine. The Stewards of the Jockey Club subsequently gave notice that they had established a threshold level for theobromine in urine of 2 micrograms/ml. PMID- 2209521 TI - Effects of three anthelmintic schedules on the incidence of colic in horses. AB - Four privately owned herds (25 to 49 animals per herd) were used in a five-year trial designed to evaluate the effect of anthelmintic schedules on the incidence of colic. These herds had been treated bi-monthly with non-ivermectin, non benzimidazole drugs for two years before the trial. Prior parasitological studies showed that they had substantial pre-treatment faecal egg counts (900 to 2200 eggs per gramme), and that they were infected with benzimidazole-resistant cyathostomes. In Years 1 and 2 of the trial, all herds (A, B, C, D) were treated bi-monthly with non-ivermectin anthelmintics (Schedule I). In Years 3 to 5, Herd A received monthly non-ivermectin anthelmintics (Schedule II) and Herd C was treated with bi-monthly ivermectin (Schedule III). Herd B was treated with Schedule II in Years 3 and 4 and Schedule III in Year 5. Herd D was maintained on Schedule I throughout the study period. In each herd, the incidence of colic, while on Schedule I, was compared to the incidence while on Schedule II or III. The risk of colic for horses on Schedule I was 2.61 to 13.04 times that of the same horses while on Schedule II and 2.27 to 9.64 times that of the same horses while on Schedule III. In Herd D, treated according to Schedule I for five years, the incidence of colic did not vary significantly throughout the study period. More effective anthelmintic treatment schedules decreased the incidence of colic in these herds, supporting the conclusion that bimonthly treatment with non ivermectin drugs may not maximise horses' health in all management conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2209522 TI - The effects of phenylbutazone on the intestinal mucosa of the horse: a morphological, ultrastructural and biochemical study. AB - Phenylbutazone, a non-steroidal anti-inflammatory drug known to produce intestinal erosions, was administered intravenously (13.46 mg/kg bodyweight) to 12 horses which were killed after 24, 48, 72 and 96 h. Eight untreated horses served as controls. Annular erosions in the duodenum and mucosal necrosis in the colon were seen after 48 h which progressed in severity. The erosions were characterised by sloughing of the surface epithelium, subepithelial cleft and bleb formation, necrosis of the lamina propria, degeneration of the walls of subsurface capillaries and microthrombosis. Large numbers of neutrophils with abundant fibrin and cellular debris were present at the erosion sites. Ultrastructurally, there was swelling of the endothelium of capillaries and small vessels, and of pericyte and smooth muscle cytoplasm in arterioles. In capillaries and post capillary venules, the endothelium ranged from swollen to lysed and necrotic. Extensive extravasation of erythrocytes and oedema were seen. These lesions were not seen in the control horses. Phenylbutazone produces a microvascular injury associated with the formation of duodenal and colonic erosions in horses. The duodenal and colonic mucosa were assayed at 48 and 96 h for prostacyclin and PGE2. There was no statistically significant difference between prostaglandin levels in the mucosa of control and treated horses. It was concluded that there was no correlation between mucosal prostaglandin levels and intestinal erosions after 48 h. PMID- 2209523 TI - Equine synovial tendon sheaths and bursae: an histological and scanning electron microscopical study. AB - The structure of equine synovial tendon sheaths and bursae has been examined by light and scanning electron microscopy. Tissue samples were obtained from horses of various types and ages with no clinical evidence of sheath or bursal disorders. The interior of both structures was lined by a cellular layer superimposed on a vascular zone supported by a fibrous layer. The pattern of cell distribution of the lining varied from site to site within the same structure depending on the nature of the underlying tissue and on the amount of movement to which the structure was subjected. The cellular layer was predominantly fibrous in nature with scanty, widely separated fibroblasts (eg where it lines the palmar ligament, tendons and paratendons). In the mesotendon and bursal extremities, where the lining is subjected to a positive degree of movement, the cellular layer was areolar in type with well established folds populated by abundant cells oval to round in shape. In foals and yearlings, the supportive layer was mainly around the areolar with patches of adipose tissue; which were gradually replaced by fibrous tissue as the animal grew. PMID- 2209524 TI - Haemodynamic effects of small volume hypertonic saline in experimentally induced haemorrhagic shock. AB - A comparison of the haemodynamic benefits of small volume hypertonic saline (2,400 mOsm/litre) versus isotonic saline (300 mOsm/litre) was conducted in 12 adult horses using a haemorrhagic shock model. The horses were anaesthetised and intravascular catheters placed for the measurement of haemodynamic data. Mean systemic arterial pressure was then reduced to 50 to 60 mmHg by controlled haemorrhage and maintained at that level for 40 mins. Cardiac output, stroke volume, mean systemic arterial pressure, plasma volume and urine production decreased significantly following blood loss. Hypertonic or isotonic saline was administered randomly by intravenous infusion and haemodynamic data recorded for a 2 h period. Treatment with hypertonic saline produced rapid elevations in cardiac output, stroke volume, mean systemic and pulmonary arterial pressures, cardiac contractility and urine output, and was accompanied by expansion of the plasma volume. The changes in cardiac output and stroke volume were maintained for the duration of the recording period, whereas increases in mean systemic arterial pressure were not as remarkable. Infusion of isotonic saline caused only transient increases in cardiac output and mean systemic and pulmonary arterial pressure, and cardiac output; urine output and plasma volume did not change. This study indicates that hypertonic saline produces haemodynamic improvements in experimentally induced haemorrhagic shock in horses. PMID- 2209525 TI - Disposition of oxytetracycline in horses, ponies and donkeys after intravenous administration. PMID- 2209526 TI - Fibre size and composition in the middle gluteal muscle of the Andalusian horse. PMID- 2209527 TI - A radiographic survey of tibiotarsal osteochondrosis in a selected population of trotting horses in Denmark and its possible genetic significance. PMID- 2209528 TI - A case of primary autoimmune haemolytic anaemia in a pony. PMID- 2209529 TI - Four cases of equine bone lesions caused by Pythium insidiosum. PMID- 2209531 TI - Productivity, or quality of work as the decisive factor in marketing ergonomics? Design considerations for a new ergonomic welding-table. AB - Quality tools should be designed from the starting point of adjusting tasks and equipment to human possibilities and limitations. Companies should consider an investment in ergonomic equipment as a profitable addition to indispensable productive machinery. As an example to support this statement, the authors describe the health risks of welders and the possible solutions. As the result of investigations a list of requirements was drafted for a product that would have less of the disadvantages of the products mentioned. The designed product, the 'ergonomic welding-table', aims to be a quality tool for welders working at small and medium-sized tasks. The product consists of a cabin (2.35 m wide) with a built-in ventilator for very efficient welding-fume extraction (90%-95%). Welders can set their preferred working height at any time. Another advantage is the option of performing the welding task while standing or sitting. The results of user-evaluation among welders and purchasers indicates considerable satisfaction. PMID- 2209530 TI - The median cleft of the lower lip and mandible and its surgical correction in a donkey. PMID- 2209533 TI - A design method for product safety. AB - The Product Safety Method is a method to detect and solve product safety problems. It consists of two parts, analysis and synthesis. The analysis can be used to evaluate products on their safety, by gaining insight into possible accidents with the product and into critical factors connected with either the product, the actions of the user or environmental conditions. The synthesis offers a structured list of solution strategies for the generation of effective solutions to the detected safety problems. The method may be used by both ergonomists and product designers. In conclusion problems in determining the usability and effectiveness of the method are discussed as well as how to adapt the method to fit the world of professional design practice. PMID- 2209532 TI - Anthropometric data of children for non-specialist users. AB - In a pilot study, 33 anthropometric variables were measured on 633 children aged 0-5.5 years. The variables where chosen on the basis of international standards and on the results of preliminary analysis of accidents. Methodical aspects of this pilot study are presented in this paper, followed by two applications: anthropometric aspects of current regulations for cribs, playpens and toys; anthropometric aspects in the selection of wheelchairs for children. The paper concludes with a discussion on how to present anthropometric data for non-special users. PMID- 2209534 TI - Research into accidents as a design tool. AB - Product liability legislation presses to gain more insight into the occurrence of accidents with consumer products, to the benefit of both producers and consumers. In this paper research is presented that was carried out in order to provide this insight. The research consisted of recording the reconstruction of accidents by the victims. The design relevance of the comprehensive data was assessed by a panel of industrial designers. The results are discussed in view of the development of a method that is actually applicable by industrial designers, in order to anticipate possible ways of use that might result in accidents. It is argued that the availability and the application of such a method would not only contribute to the prevention of accidents, but might also positively affect the marketing position of a product. PMID- 2209536 TI - Expression of a yeast-derived invertase in the cell wall of tobacco and Arabidopsis plants leads to accumulation of carbohydrate and inhibition of photosynthesis and strongly influences growth and phenotype of transgenic tobacco plants. AB - Chimeric genes consisting of the coding sequence of the yeast invertase gene suc 2 and different N-terminal portions of the potato-derived vacuolar protein proteinase inhibitor II fused to the 35S CaMV promoter and the poly-A site of the octopine synthase gene were transferred into tobacco and Arabidopsis thaliana plants using Agrobacterium based systems. Regenerated transgenic plants display a 50- to 500-fold higher invertase activity compared to non-transformed control plants. This invertase is N-glycosylated and efficiently secreted from the plant cell leading to its apoplastic location. Whereas expression of the invertase does not lead to drastic changes in transgenic Arabidopsis thaliana plants, transgenic tobacco plants show dramatic changes with respect to development and phenotype. Expression of the invertase leads to stunted growth due to reduction of internodal distances, to development of bleached and/or necrotic regions in older leaves and to suppressed root formation. In mature leaves, high levels of soluble sugars and starch accumulate. These carbohydrates do not show a diurnal turnover. The accumulation of carbohydrate is accompanied by an inhibition of photosynthesis, and in tobacco, by an increase in the rate of respiration. Measurements in bleached versus green areas of the same leaf show that the bleached section contains high levels of carbohydrates and has lower photosynthesis and higher respiration than green sections. It is concluded that expression of invertase in the cell wall interrupts export and leads to an accumulation of carbohydrates and inhibition of photosynthesis. PMID- 2209535 TI - EMBO medal review. On transferring genes into stem cells and mice. PMID- 2209537 TI - Primary structure, genomic organization and heterologous expression of a glucose transporter from Arabidopsis thaliana. AB - Both genomic and full length cDNA clones of an Arabidopsis thaliana sugar carrier, STP1, have been obtained using a cDNA clone of the H+/hexose cotransporter from the green alga Chlorella kessleri as hybridization probe. The peptide predicted from these sequences in 522 amino acids long and has a molecular weight of 57,518 kd. This higher plant sugar carrier contains 12 putative transmembrane segments and is highly homologous to the H+/hexose cotransporter from Chlorella, with an overall identity in the amino acid sequence of 47.1%. It is also homologous to the human HepG2 glucose transporter (28.4%), and other sugar carriers from man, rat, yeast and Escherichia coli. The definite proof for the function of the STP1 protein as a hexose transporter and data on its substrate specificity were obtained by heterologous expression in the fission yeast Schizosaccharomyces pombe. Transformed yeast cells transport D-glucose with a 100-fold lower KM value than control cells. Moreover only the transformed cells were able to accumulate the non-metabolizable D-glucose analogue 3-O-methyl-D glucose, indicating that the Arabidopsis carrier catalyses an energy dependent, active uptake of hexoses. Expression of STP1 mRNA is low in heterotrophic tissues like roots or flowers. High levels of expression are found in leaves. PMID- 2209538 TI - Extrachromosomal homologous recombination and gene targeting in plant cells after Agrobacterium mediated transformation. AB - We determined whether T-DNA molecules introduced into plant cells using Agrobacterium are suitable substrates for homologous recombination. For the detection of such recombination events different mutant versions of a NPTII construct were used. In a first set of experiments protoplasts of Nicotiana tabacum SR1 were cocultivated with two Agrobacterium tumefaciens strains. Each strain contained a different T-DNA, one carrying a 5' deleted NPTII gene and the other a NPTII gene with a 3' deletion. A restored NPTII gene was found in 1-4% of the protoplasts that had been cotransformed with both T-DNAs. Restoration of the NPTII gene could only be the consequence of homologous recombination between the two different T-DNAs in the plant cell, since the possibility of recombination in Agrobacterium was excluded in control experiments. In subsequent experiments was investigated the potential use of Agrobacterium for gene targeting in plants. A transgenic tobacco line with a T-DNA insertion carrying a defective NPTII gene with a 3' deletion was transformed via Agrobacterium with a T-DNA containing a defective NPTII repair gene. Several kanamycin resistant plant lines were obtained with an intact NPTII gene integrated in their genome. In one of these lines the defective NPTII gene at the target locus had been properly restored. Our results show that in plants recombination can occur between a chromosomal locus and a homologous T-DNA introduced via A. tumefaciens. This opens the possibility of using the Agrobacterium transformation system for site directed mutagenesis of the plant genome. PMID- 2209539 TI - A 3' transcriptional enhancer regulates tissue-specific expression of the human CD2 gene. AB - A strong lymphocyte-specific transcriptional enhancer was identified within a DNase I hypersensitive site at the 3' end of the human CD2 gene. Full activity, in a transient expression assay, was contained within a region of 550 bp (minimal enhancer). T cells which express CD2 could use the enhancer to activate transcription from the reporter gene chloramphenicol acetyltransferase in the context of a heterologous promoter. Lower levels of transcription were detected in non-CD2-expressing T cells and in B cells. In contrast, the enhancer did not function in the epithelial cell line HeLa or in Colo 320 HSR, a cell line of neuroendocrine origin. Low levels of enhancement were detectable from two core regions, which acted synergistically with other cis-acting sequences to generate the complete enhancer. DNase I footprinting studies identified six cis-acting sequences to which proteins bound. Five of these sequence motifs were novel; the sixth was a canonical cAMP response element. Topoisomerase II, and scaffold attachment region consensus sequences were also found within an A/T-rich area downstream of the minimal enhancer. Neither region was bound to the nuclear matrix. The CD2 enhancer is modular in structure, it is constructed of novel cis acting sequences and it is a major component of the regulatory system that controls expression of the CD2 gene. PMID- 2209540 TI - The product of the c-ets-1 proto-oncogene and the related Ets2 protein act as transcriptional activators of the long terminal repeat of human T cell leukemia virus HTLV-1. AB - The c-ets-1 proto-oncogene and the related c-ets-2 gene encode related nuclear chromatin-associated proteins which bind DNA in vitro. To investigate the possibility that Ets1 and Ets2 are transcriptional activators, we analyzed the ability of these proteins to trans-activate promoter/enhancer sequences in transient co-transfection experiments. A CAT construct driven by the long terminal repeat of the human T cell leukemia virus, HTLV-1 was found to be trans activated by both Ets1 and Ets2 in NIH3T3 and HeLa cells. The increased levels of CAT activity were paralleled by increased levels of correctly initiated CAT mRNA. Mutant Ets1 proteins unable to accumulate in the nucleus were found to be inactive. An ets-responsive sequence between positions -117 and -160 of the LTR was identified by analyses of a series of 5' deletion mutants of the HTLV-1 LTR and of dimerized versions of specific motifs of the LTR enhancer region. Using a gel shift binding assay, Ets1 was found to bind specifically to an oligonucleotide corresponding to region -117 to -160. This sequence, which also contributes to Tax1 responsiveness of the HTLV-1 LTR, is characterized by the presence of four repeats of a pentanucleotide sequence of the type CC(T/A)CC. Competition experiments show that integrity of repeats 1 and 4 is important for Ets1 binding. These results show that Ets1 and Ets2 are sequence-specific transcriptional activators. In view of the high level expression of Ets1 in lymphoid cells, Ets1 could be part of the transcription complex which mediates the response to Tax1 and the control of HTLV-1 replication. More generally, Ets1 and Ets2 could regulate transcription of cellular genes. PMID- 2209541 TI - Microtubule perturbation retards both the direct and the indirect apical pathway but does not affect sorting of plasma membrane proteins in intestinal epithelial cells (Caco-2). AB - Endogenous plasma membrane proteins are sorted from two sites in the human intestinal epithelial cell line Caco-2. Apical proteins are transported from the Golgi apparatus to the apical domain along a direct pathway and an indirect pathway via the basolateral membrane. In contrast, basolateral proteins never appear in the apical plasma membrane. Here we report on the effect of the microtubule-active drug nocodazole on the post-synthetic transport and sorting of plasma membrane proteins. Pulse-chase radiolabeling was combined with domain specific cell surface assays to monitor the appearance of three apical and one basolateral protein in plasma membrane domains. Nocodazole was found to drastically retard both the direct transport of apical proteins from the Golgi apparatus and the indirect transport (transcytosis) from the basolateral membrane to the apical cell surface. In contrast, neither the transport rates of the basolateral membrane nor the sorting itself were significantly affected by the nocodazole treatment. We conclude that an intact microtubular network facilitates, but is not necessarily required for, the transport of apical membrane proteins along the two post-Golgi pathways to the brush border. PMID- 2209542 TI - The recognition component of the N-end rule pathway. AB - The N-end rule-based degradation signal, which targets a protein for ubiquitin dependent proteolysis, comprises a destabilizing amino-terminal residue and a specific internal lysine residue. We report the isolation and functional analysis of a gene (UBR1) for the N-end recognizing protein of the yeast Saccharomyces cerevisiae. UBR1 encodes a approximately 225 kd protein with no significant sequence similarities to other known proteins. Null ubr1 mutants are viable but are unable to degrade the substrates of the N-end rule pathway. These mutants are partially defective in sporulation and grow slightly more slowly than their wild type counterparts. The UBR1 protein specifically binds in vitro to proteins bearing amino-terminal residues that are destabilizing according to the N-end rule, but does not bind to otherwise identical proteins bearing stabilizing amino terminal residues. PMID- 2209543 TI - Purified presequence binding factor (PBF) forms an import-competent complex with a purified mitochondrial precursor protein. AB - In vitro mitochondrial import of the purified precursor form (pOTC) of rat ornithine carbamoyltransferase (OTC) is stimulated by a cytosolic factor(s) contained in rabbit reticulocyte lysate. A protein factor that binds to pOTC but not to mature OTC and was named presequence binding factor or PBF, was purified 91,000-fold from the lysate by affinity chromatography using pOTC-bound Sepharose, DEAE-5PW HPLC and sucrose gradient centrifugation. The purified PBF migrated as a single polypeptide of 50,000 daltons on SDS-PAGE. On sucrose gradients, urea-denatured pOTC sedimented to the bottom, whereas PBF sedimented with an S20,w value of 5.5S. When pOTC and PBF were centrifuged together, both polypeptides sedimented as a complex of 7.1S. Formation of the pOTC-PBF complex was inhibited by micromolar concentrations of the synthetic presequence of pOTC and those of other mitochondrial precursor proteins. The purified PBF markedly stimulated the import of purified or in vitro synthesized pOTC into the mitochondria. PBF-stimulated pOTC import was further enhanced by a 70 kd heat shock protein (hsp 70) purified from yeast; the hsp70 alone had little effect. Thus, PBF binds to the presequence portion of the precursors and may hold them in a transport-competent form in cooperation with hsp70. PMID- 2209544 TI - The adenylate cyclase/protein kinase cascade regulates entry into meiosis in Saccharomyces cerevisiae through the gene IME1. AB - Entry into meiosis in Saccharomyces cerevisiae cells is regulated by starvation through the adenylate cyclase/cAMP-dependent protein kinase (AC/PK) pathway. The gene IME1 is also involved in starvation control of meiosis. Multicopy IME1 plasmids overcome the meiotic deficiency of bcy1 and of RASval19 diploids. Double mutants ime1 cdc25 and ime1 ras2 are sporulation deficient. These results suggest that IME1 comes after the AC/PK cascade. Furthermore, the level of IME1 transcripts is affected by mutations in the AC/PK genes CDC25, CYR1 and BCY1. Moreover, the addition of cAMP to a cyr1-2 diploid suppresses IME1 transcription. The presence in a bcy1 diploid of IME1 multicopy plasmids does not cure the failure of bcy1 cells to arrest as unbudded cells following starvation and to enter the G0 state (thermotolerance, synthesis of unique G0 proteins). This indicates that the pathway downstream of the AC/PK cascade branches to control meiosis through IME1, and to control entry into G0 and cell cycle initiation, independently of IME1. PMID- 2209545 TI - p40MO15, a cdc2-related protein kinase involved in negative regulation of meiotic maturation of Xenopus oocytes. AB - The clone MO15 which codes for a 40 kd protein (p40MO15) with 40% amino acid identity to the human cdc2 protein kinase has been isolated from a Xenopus cDNA library using a synthetic oligonucleotide probe. MO15 mRNA is accumulated during oogenesis, becomes de-adenylated during meiotic maturation, and is degraded after the mid-blastula-transition stage of embryogenesis. Translation of p40MO15 is restricted to non-mature oocytes. Specific inhibition of p40MO15 synthesis in stage VI oocytes by antisense oligonucleotide depletion of MO15 mRNA increases the rate of progesterone induced H1 kinase activation and oocyte maturation. This effect can be reversed by subsequent injection of synthetic MO15 mRNA. These results suggest that p40MO15 is involved in negatively regulating meiosis. PMID- 2209546 TI - Characterization of recombinant human factor IX expressed in transgenic mice and in derived trans-immortalized hepatic cell lines. AB - Transgenic mice were generated in which 5 kb of the 5' flanking promoter region of the human Factor IX (FIX) gene fused to various FIX constructs (gene, minigene and cDNA) were stably integrated in the germ line. Several transgenic mouse lines expressed high circulating levels of active and correctly processed recombinant human FIX. The presence of at least one FIX intron had a positive effect on the expression. The FIX transgenes were expressed in a tissue-specific manner in the liver of transgenic mice. By crossing transgenic mice synthesizing FIX with others prone to develop hepatoma, progeny which co-express the transgenes in hepatocytes were obtained. Hepatoma-derived cell lines were shown to have a differentiated phenotype and secrete active human FIX for many generations. PMID- 2209547 TI - Site-specific recombination of the tal-1 gene is a common occurrence in human T cell leukemia. AB - The tal-1 gene is altered as a consequence of the t(1;14) (p32;q11) chromosome translocation observed in 3% of patients with T cell acute lymphoblastic leukemia (T-ALL). tal-1 encodes a helix-loop-helix (HLH) domain, a DNA binding and dimerization motif found in a number of proteins involved in cell growth and differentiation. We now report that an additional 25% of T-ALL patients bear tal 1 gene rearrangements that are not detected by karyotype analysis. These rearrangements result from a precise 90 kb deletion (designated tald) that arises independently in different patients by site-specific DNA recombination. Since the deletion junctions resemble the coding joints of assembled immunoglobulin genes, tald rearrangements are likely to be mediated by aberrant activity of the immunoglobulin recombinase. Moreover, t(1;14)(p32;q11) translocations and tald rearrangements disrupt the coding potential of tal-1 in an equivalent manner, and thereby generate a common genetic lesion shared by a significant proportion of T ALL patients. PMID- 2209548 TI - Mutants of the EcoRI endonuclease with promiscuous substrate specificity implicate residues involved in substrate recognition. AB - The EcoRI restriction endonuclease cleaves DNA molecules at the sequence GAATTC. We devised a genetic screen to isolate EcoRI mutants with altered or broadened substrate specificity. In vitro, the purified mutant enzymes cleave both the wild type substrate and sites which differ from this by one nucleotide (EcoRI star sites). These mutations identify four residues involved in substrate recognition and catalysis that are different from the amino acids proposed to recognize the substrate based on the EcoRI-DNA co-crystal structure. In fact, these mutations suppress EcoRI mutants altered at some of the proposed substrate binding residues (R145, R200). We argue that these mutations permit cleavage of additional DNA sequences either by perturbing or removing direct DNA-protein interactions or by facilitating conformational changes that allosterically couple substrate binding to DNA scission. PMID- 2209550 TI - A set of tRNAs that lack either the T psi C arm or the dihydrouridine arm: towards a minimal tRNA adaptor. AB - The mitochondrial DNA (mtDNA) molecules of the nematode worms, Caenorhabditis elegans and Ascaris suum contain 22 putative genes for non-standard forms of tRNAs. The inferred transcripts can be folded into 20 separate structures each resembling a tRNA whose T psi C arm and variable loop are replaced with a simple loop of 6-12 nucleotides. In two further structures [that resemble tRNAs for ser(UCN) and ser(AGN)], the dihydrouridine arm is replaced by a loop of 5-8 nucleotides. By hybridizing mt-tRNA gene-specific oligonucleotide probes to nematode RNAs, we have obtained evidence for transcription of at least nine C.elegans and three A.suum mt-tRNA genes. Each transcript (tRNA) is the exact size predicted from the respective DNA sequence, to which three nucleotides, presumably CCA, have been added following transcription. An exception was C.elegans mt-tRNAasn, most molecules of which had one nucleotide (plus CCA) more than predicted from the gene. The data presented strongly support the conclusion that the functional mt-tRNAs of nematode worms are direct transcripts (with only CCA addition) of the structurally unusual mt-tRNA genes. There is no evidence of trans-splicing or RNA editing to add the sequences missing from these nonstandard tRNAs. We presume, therefore, that the non-standard forms are active in mitochondrial protein synthesis. PMID- 2209549 TI - A short cis-acting sequence is required for hepatitis B virus pregenome encapsidation and sufficient for packaging of foreign RNA. AB - The selective encapsidation of the hepadnaviral RNA pregenome from an excess of other viral and cellular mRNAs predicts specific protein-RNA interactions involving one or several sites on the pregenome. Using deletion analysis in a transient expression/packaging system in which all relevant viral proteins are provided in trans from a packaging-deficient helper genome, we identified near the 5'-end of the pregenome a 137 nucleotide sequence that is necessary and sufficient for RNA encapsidation; other parts of the 3 kb pregenome were found not to contribute to this process. The encapsidation sequence, which we call epsilon, possesses several interesting features with implications for the pregenome's function in RNA packaging, RNA translation and reverse transcription. (i) epsilon contains several indirect repeat sequences, suggesting a high degree of secondary structure, (ii) epsilon overlaps with the start signal for core gene translation, suggesting a mechanism to regulate the alternative use of the pregenome as core mRNA, (iii) epsilon does not contain the direct repeat sequences known to be involved in the initiation of viral DNA synthesis. Finally, our deletion analysis suggests that ribosomes translating the epsilon sequence from the precore start codon may interfere with genomic RNA packaging. PMID- 2209552 TI - Identification of barley stripe mosaic virus genes involved in viral RNA replication and systemic movement. AB - Barley stripe mosaic hordeivirus (BSMV) has a tripartite positive-sense RNA genome which encodes seven major polypeptides. Infectious in vitro transcripts derived from full-length wild-type and mutant cDNA clones have been used to investigate the contribution made by various BSMV gene products to viral RNA replication and systemic movement. We show that whereas all three of the BSMV RNA components are required for plant infection, RNAs alpha and gamma can replicate together in barley protoplasts, and therefore RNA beta must encode functions required for systemic invasion of plants. The alpha a and gamma a proteins, which contain helicase and RNA polymerase sequence motifs, together comprise the essential virus-encoded components of BSMV RNA replicase. A second BSMV protein (beta b) which contains a helicase motif is not required for RNA replication. A small cysteine-rich protein (gamma b) is dispensable for infection of plants, but in its absence the accumulation of viral coat (beta a) and beta b proteins is significantly reduced. In addition, mutations in both the gamma b and gamma a (replicase) proteins can affect the systemic movement phenotype. PMID- 2209551 TI - Photoregulated gene expression may involve ubiquitous DNA binding proteins. AB - Several promoter elements have previously been shown to influence the expression of the cab-E gene in Nicotiana plumbaginifolia. Here we demonstrate, by electrophoretic mobility shift and methylation interference assays, that a complex pattern of protein-DNA interactions characterizes this promoter. Among the multiple proteins identified, we focused on five different factors which either occupied important regulatory elements and/or were present in relatively large amounts in nuclear extracts. All of these proteins were distinguished on the basis of their recognition sequence and other biochemical parameters. One, GBF, interacted with a single sequence within the cab-E promoter homologous to the G-box found in many photoregulated and other plant promoters. A second factor, GA-1, bound to the GATA element which is located between the CAAT and TATA boxes of the cab-E and all other LHCII Type I CAB promoters. GA-1 also interacted in vitro with the I-boxes of the Arabidopsis rbcS-1A promoter and the as-2 site of the CaMV 35S promoter. Two other factors, GC-1 and AT-1, bound to multiple recognition sites localized within the GC-rich and AT-rich elements, respectively. GT-1, a protein which interacts with promoters of other light regulated genes, bound to seven distinct sites distributed throughout the cab-E promoter. PMID- 2209553 TI - Identification and localization of high molecular weight proteins in insect flight and leg muscle. AB - Thick and thin filaments in asynchronous flight muscle overlap nearly completely and thick filaments are attached to the Z-disc by connecting filaments. We have raised antibodies against a fraction of Lethocerus flight muscle myofibrils containing Z-discs and associated filaments and also against a low ionic strength extract of myofibrils. Monoclonal antibodies were obtained to proteins of 800 kd (p800), 700 kd (p700), 400 kd (p400) and alpha-actinin. The positions of the proteins in Lethocerus flight and leg myofibrils were determined by immunofluorescence and electron microscopy. p800 is in connecting filaments of flight myofibrils and in A-bands of leg myofibrils. p700 is in Z-discs of flight myofibrils and an immunologically related protein, p500, is in leg muscle Z discs. p400 is in M-lines of both flight and leg myofibrils. Preliminary DNA sequencing shows that p800 is related to vertebrate titin and nematode twitchin. Molecules of p800 could extend from the Z-disc a short way along thick filaments, forming a mechanical link between the two structures. All three high molecular weight proteins probably stabilize the structure of the myofibril. PMID- 2209554 TI - Specific structural alteration of the influenza haemagglutinin by amantadine. AB - Amantadine hydrochloride specifically blocks the release of virus particles from H7 influenza virus infected cells. This appears to be the direct consequence of an amantadine induced change in the haemagglutinin (HA) to its low pH conformation. The effect is indirect and mediated via interaction of the drug with the M2 protein since mutants altered in this component alone are insensitive to amantadine. The timing of drug action, some 15-20 min after synthesis, and its coincidence with proteolytic cleavage indicates that the modifications to HA occur late during transport but prior to insertion into the plasma membrane. Reversal by mM concentrations of amines and 0.1 microM monensin indicates that amantadine action causes a reduction in intravesicular pH which triggers the conformational change in HA. We conclude, therefore, that the function of M2 inhibited by amantadine is involved in counteracting the acidity of vesicular compartments of the exocytic pathway in infected cells and is important in protecting the structural integrity of the acid-sensitive glycoprotein. PMID- 2209555 TI - ATP and cytosol requirements for transferrin recycling in intact and disrupted MDCK cells. AB - We have developed an in vitro system for studying membrane transport during receptor-mediated endocytosis. Using nitrocellulose disruption to permeabilize selectively the apical domain of filter-grown MDCK cells, the recycling of receptor-bound transferrin (Tfn) from an intracellular pool was reconstituted in vitro with a rate and efficiency similar to that of intact cells. Tfn and Tfn receptor recycling from endosomes back to the cell surface was dependent on added ATP and cytosol-derived proteins. Thus, incubation of intact cells under conditions of ATP depletion resulted in the clearance of Tfn receptors from the basolateral membrane, this was reversible upon removal of the energy poisons. Reappearance of previously internalized receptors could also be obtained in disrupted cells but required the addition of both ATP and cytosol to the assay mixture. Similarly, when intact cells were allowed to internalize labeled Tfn prior to disruption, efficient and rapid release of ligand back into the medium was markedly stimulated by ATP and cytosol. Recycling was judged to be both selective and vectorial since only the expected small fraction of a previously internalized horseradish peroxidase was released after addition of ATP and cytosol, and release was primarily into the basal medium. While the cytosol contributed one or more protein factors, none was sensitive to N-ethylmaleimide. Alkylation of the disrupted cells, however, did inactivate recycling. PMID- 2209556 TI - Targeting of a lysosomal membrane protein: a tyrosine-containing endocytosis signal in the cytoplasmic tail of lysosomal acid phosphatase is necessary and sufficient for targeting to lysosomes. AB - Lysosomal acid phosphatase (LAP) is synthesized as a transmembrane protein with a short carboxy-terminal cytoplasmic tail of 19 amino acids, and processed to a soluble protein after transport to lysosomes. Deletion of the membrane spanning domain and the cytoplasmic tail converts LAP to a secretory protein, while deletion of the cytoplasmic tail as well as substitution of tyrosine 413 within the cytoplasmic tail against phenylalanine causes accumulation at the cell surface. A chimeric polypeptide, in which the cytoplasmic tail of LAP was fused to the ectoplasmic and transmembrane domain of hemagglutinin is rapidly internalized and tyrosine 413 of the LAP tail is essential for internalization of the fusion protein. A chimeric polypeptide, in which the membrane spanning domain and cytoplasmic tail of LAP are fused to the ectoplasmic domain of the Mr 46 kd mannose 6-phosphate receptor, is rapidly transported to lysosomes, whereas wild type receptor is not transported to lysosomes. We conclude that a tyrosine containing endocytosis signal in the cytoplasmic tail of LAP is necessary and sufficient for targeting to lysosomes. PMID- 2209557 TI - Signal sequence for generation of mRNA 3' end in the Saccharomyces cerevisiae GAL7 gene. AB - We have identified a signal sequence (designated core signal) necessary to specify formation of mRNA 3' end of the GAL7 gene in Saccharomyces cerevisiae within a DNA segment 26 bp long. The sequence was located 4-5 nucleotides upstream from the 3' end, i.e. the polyadenylation site, of the GAL7 mRNA. Replacement of a DNA segment encompassing the polyadenylation site with a pBR322 DNA, leaving the core signal intact, resulted in alteration of the mRNA 3' end by several nucleotides, suggesting the existence of an additional signal (designated end signal) at or near the polyadenylation site. The normal end formation was abolished when the core signal was placed in the reverse orientation. A considerable fraction of pre-mRNA synthesized in vitro with SP6 RNA polymerase on the template of a DNA fragment containing these signals was cleaved and polyadenylated presumably at the in vitro 3' end during incubation in a cell-free system of yeast. By contrast pre-mRNA synthesized on the template with the core signal alone was processed but much less efficiently. No such processing was seen when the pre-mRNA either lacked the core signal or contained it in the reverse orientation. PMID- 2209558 TI - The Xenopus laevis poly(A) binding protein is composed of multiple functionally independent RNA binding domains. AB - A family of eukaryotic RNA binding proteins is defined by the conserved RNP motif. The poly(A) binding protein has four such motifs. We report on the isolation and structural characterization of several variant cDNA clones, as well as of a gene encoding this protein in Xenopus laevis embryos. Wild-type protein as well as truncated versions carrying isolated single motifs or artificial combinations of two and more such elements were characterized for their ability to bind specifically to RNA homopolymers. Three of the isolated repeats were functional in specific RNA binding, whereas the N-terminal RNP motif was non functional. Combinatorial effects in RNA binding were measured with constructs carrying multiple repeats, which were not predictable from the activity of isolated domains. PMID- 2209561 TI - Quantitative estimation of the genetic risk associated with the induction of heritable translocations at low-dose exposure: ethylene oxide as an example. AB - This paper explores how quantitative risk assessment methods might be extended to analysis of risks to the human germ line. High inhalation exposures to ethylene oxide are reported to cause heritable translocations in male mice with a steep and nonlinear dose-response-curve. We explore quantitative estimation of risk to humans from low exposures based on these animal data, addressing questions of tissue dosimetry for this alkylating agent, expected equivalency of doses across species, germ-cell sensitivity, and extrapolation of dose-response relationship to low exposure levels. Various dose-response models are discussed in terms of their applicability to genetic end points and their ability to reflect the underlying basis of induced heritable translocations. PMID- 2209560 TI - Periodic formation of the oriC complex of Escherichia coli. AB - We examined formation of an oriC-membrane complex through the chromosome replication cycle by dot-blot hybridization using an oriC plasmid as a probe. In a wild-type culture synchronized for chromosome replication, oriC complex formation was observed periodically and transiently corresponding to the replication initiation event. Prior to initiation of replication the oriC complex was recovered in the outer membrane fraction as well as at the time of initiation of replication. Moreover, periodic formation of the oriC complex was observed even when further initiation of replication was suppressed by culturing an initiation ts mutant at the restrictive temperature. Similar periodic formation of the oriC complex was also observed when DNA elongation was inhibited by addition of nalidixic acid to the culture. However, the second periodic peak did not appear when rifampicin or chloramphenicol was added. Cells which formed the oriC complex at the restrictive temperature could immediately initiate chromosome replication when the cells were transferred to the permissive temperature. We conclude that the oriC region of Escherichia coli forms a specific complex periodically just before and at the time of initiation of chromosome replication and that oriC complex formation is a prerequisite for initiation of chromosome replication. PMID- 2209559 TI - E.coli Fis protein activates ribosomal RNA transcription in vitro and in vivo. AB - An upstream activation region (UAR) contributes to the extremely high activity of the Escherichia coli ribosomal RNA promoter, rrnB P1, increasing its activity 20- to 30-fold over that of the same promoter lacking the UAR. We have used DNase footprinting to define three specific sites in the rrnB P1 UAR that bind Fis, a protein identified previously by its role in recombinational enhancer function in other systems. We find that purified Fis activates transcription from promoters containing these sites 10- to 20-fold in vitro at concentrations correlating with the filling of these sites. Three approaches indicate that Fis contributes to the function of the UAR in vivo. First, there is a progressive loss in the activity of rrnB P1-lacZ fusions as Fis binding sites are deleted. Second, an rrnB P1 promoter with a mutation in a Fis binding site has 5-fold reduced transcription activity in vivo, dramatically reduced Fis binding in vitro, and shows no Fis dependent transcription activation in vitro. Third, upstream activation is reduced 5-fold in a Fis- strain. We show that rRNA promoters derepress in response to the loss of Fis in vivo in accord with the predictions of the negative feedback model for rRNA regulation. We find that fis is not essential for the function of two control systems known to regulate rRNA, growth rate dependent control and stringent control. On the basis of these results, we propose roles for Fis and the upstream activation system in rRNA synthesis. PMID- 2209563 TI - Perspectives and future directions for genetic risk assessment. PMID- 2209562 TI - Concentration-response curves for ethylene-oxide-induced heritable translocations and dominant lethal mutations. AB - Male mice were subjected to repeated inhalation exposures to different concentrations (165, 204, 250, or 300 ppm) of ethylene oxide (EtO) during an 8.5 week period. Transmitted clastogenic effects of these exposures were measured in terms of induction of dominant lethal mutations and heritable translocations. The concentration-response curves for both endpoints are not linear but are markedly concave upward. Significant increases in dominant lethals were detected at all concentrations, except the lowest one. In comparison, the incidences of heritable translocations were significantly increased at all concentrations. PMID- 2209564 TI - Acetaldehyde-induced mutation at the hprt locus in human lymphocytes in vitro. AB - Acetaldehyde (Aa) induces chromosomal aberration and sister chromatid exchange in a variety of test systems, but has not previously been evaluated for its ability to induce gene mutation in mammalian cells. We have studied the mutagenic effect of Aa at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in human lymphocytes in vitro by using the T-cell cloning technique and selection of mutant cell clones in medium containing thioguanine. Cells treated with 1.2-2.4 mM Aa for 24 hr or 0.2-0.6 mM Aa for 48 hr showed a dose-dependent decrease of cell survival and a 3- to 16-fold increase of the mutant frequency. The inverse relationship between cell survival and mutant frequency was linear down to a relative survival of 15%, and showed a similar slope in the 24-hr and 48-hr treatment experiments. Forty-one mutant T-cell clones derived from cultures treated with 1.2 or 2.4 mM Aa and 15 from untreated controls were expanded for DNA extraction and Southern blot analysis to study deletion mutation using a full length hprt cDNA probe, and clonal identity on the basis of T-cell receptor rearrangements. In the culture with a 16-fold increase of mutant frequency, 4 out of 10 independent mutants (40%) showed partial deletions extending beyond the 3' coding sequences of the hprt gene. Two of 22 independent mutants derived from the other treated cultures with at most a 6-fold increase of mutant frequency, and 1 of 11 independent control clones showed rearrangement of the hprt gene, none of which affected the 3'-end of the hprt gene. These results show that Aa is capable of inducing gene mutation at the hprt locus in human cells, and suggest that deletion mutation affecting the 3'-end of the gene may be a major type of Aa induced mutation of this locus. PMID- 2209565 TI - DNA adduct formation in rat alveolar type II cells: cells potentially at risk for inhaled diesel exhaust. AB - Diesel exhaust (DE) is a pulmonary carcinogen in rats. One potential mechanism for DE-induced carcinogenicity involves the interaction of the organic chemicals associated with DE soot with DNA in target cells. The purpose of this study was to determine whether peripheral lung cells, specifically alveolar type II cells, are at risk from inhaled DE. Rats were exposed 16 hr/day, 5 days/week to filtered air (controls), carbon black (CB) (6.2 mg/m3), or to diluted DE (6.2 mg/m3) for 12 weeks. CB particles were used for comparison with DE soot, because the CB particles are morphologically similar to soot particles, but are virtually devoid of adsorbed organic compounds. Type II alveolar cells were isolated by flow cytometry and DNA in the cells was analyzed for DNA adducts using the 32P postlabeling assay. There was a significant increase (approximately 4-fold) in the level of total adducts in type II cells of rats exposed to DE and CB, compared with sham-exposed rats. While exposure to CB and DE induced the formation of adducts that were not consistently seen in sham-exposed rats, exposure to these materials also appeared to increase the intensity of adducts present in type II cells from sham-exposed rats. These data underscore the importance of investigating molecular dosimetry at the biological level of the cell. We conclude that the type II alveolar cell may be a risk for damage from inhaled DE. PMID- 2209566 TI - Comparison of mutagenic activities of several peroxyacyl nitrates. AB - Salmonella typhimurium, strain TA100 was exposed to a series of peroxyacyl nitrates including peroxyacetyl nitrate (PAN), peroxypropionyl nitrate (PPN), peroxybutyryl nitrate (PBN), peroxybenzoyl nitrate (PBzN), and chloroperoxyacetyl nitrate (CPAN). Gas-phase concentrations for the individual exposures were in the high part per billion by volume ppbv range. The dose was determined from the deposition rate and measured from the net decrease of the test compound in the exposure chamber and the exposure time. The mutagenic activity for each compound determined from the dose-response relationship gave values ranging from 250 (PBN) to 6,500 (PBzN) revertants/mumols. The mutagenic activity for CPAN could not be determined, due to an interference from chloroacetaldehyde. The difficulties of quantifying the actual gas-phase chemical dose the bacteria are exposed to in this variant of the Ames test are delineated. PMID- 2209567 TI - United States Environmental Protection Agency genetic risk assessment on ethylene oxide. PMID- 2209568 TI - Introduction to the U.S. Environmental Protection Agency's genetic risk assessment on ethylene oxide. PMID- 2209569 TI - Review of the mutagenicity of ethylene oxide. AB - Ethylene oxide has been shown to be an effective mutagen in a variety of organisms ranging from bacteria to mammalian cells. There is also an association between ethylene oxide exposure and human somatic cell cytogenetic damage. Furthermore, ethylene oxide has been shown to alkylate protein and DNA at exposure levels that have been encountered occupationally. Ethylene oxide is not only effective at producing somatic cell mutations but also at inducing genetic damage in germ cells. While it is clear that ethylene oxide is a germ cell mutagen in whole mammals, the mechanism(s) by which it produces genetic lesions in germ cells is uncertain. PMID- 2209571 TI - Colony hybridisation in Escherichia coli: a rapid procedure for determining the distribution of specific classes of mutations among a number of preselected sites. AB - Colony probe oligonucleotide hybridisation was used for the unambiguous identification of DNA alterations and the determination of distributions and frequencies of forward mutation at the molecular level. To demonstrate the reliability and versatility of this technique, distributions of spontaneous and ethyl methanesulfonate (EMS)-induced mutations have been reproduced using a battery of oligonucleotide probes complementary to specific sites and classes of mutation. These studies are indicative of the diagnostic potential of oligonucleotide colony hybridisation to the characterisation of mutation; oligonucleotide hybridisation used in conjunction with a well studied mutational target provides a rapid and reliable alternative to DNA sequencing for the characterisation of all classes of mutations. PMID- 2209570 TI - Acrylamide exposure induces a delayed unscheduled DNA synthesis in germ cells of male mice that is correlated with the temporal pattern of adduct formation in testis DNA. AB - A study of meiotic and postmeiotic germ-cell-stage sensitivity of male mice to induction of unscheduled DNA synthesis (UDS) by acrylamide showed that DNA repair could be detected in early spermatocytes (after the last scheduled DNA synthesis) through about mid-spermatid stages. No DNA repair could be detected in later stages. The maximum UDS response was observed 6 hr after i.p. exposure and was about 5 times greater than the response measured immediately after treatment. This is the longest delay between chemical treatment and maximum UDS response yet observed in mouse germ cells. There was a linear relationship between the UDS response and acrylamide exposure from 7.8 to 125 mg/kg. By using 14C-labeled acrylamide it was determined that the temporal pattern of adduct formation in testes DNA paralleled that of the UDS response, with maximum binding occurring 4 to 6 hr after exposure. In contrast, the temporal pattern of adduct formation in liver DNA showed maximum binding within 1 to 2 hr after exposure and was an order of magnitude greater than that found for the testis DNA. PMID- 2209572 TI - Significant differences in the structural basis of the induction of sister chromatid exchanges and chromosomal aberrations in Chinese hamster ovary cells. AB - The structural basis of the induction of sister chromatid exchanges (SCE) and chromosomal aberrations (Cvt) in Chinese hamster ovary cells was investigated by the CASE (Computer Automated Structure Evaluation) method, an artificial intelligence-based system. Using the relevant National Toxicology Program data bases CASE identified a set of structural determinants responsible for the induction of SCE and another one for Cvt. A comparison between the structural determinants associated with SCE and Cvt revealed an overlap of only 22.6%, while the overlap between SCE and the determinants of mutagenicity in Salmonella is 54.5%. This indicates a) that the structural bases of the two phenomena differ and b) that it is likely that SCE, but not Cvt, involves a significant electrophilic/DNA-damaging component. PMID- 2209573 TI - Comparison of radon-daughter-induced effects in repair-proficient and repair deficient CHO cell lines. AB - The radiobiological effects of the radon daughter 212Bi were investigated in the Chinese hamster ovary cell line AA8 and its radiosensitive derivative EM9. EM9 cells rejoin radiation-induced DNA strand breaks more slowly than do AA8 cells. Three endpoints were examined: cell killing, G2-induced chromosome aberration frequency, and mutation induction at the hypoxanthine (guanine) phosphoribosyltransferase (HGPRT) locus. Cells were exposed to the alpha-emitter 212Bi chelated to diethylenetriaminepentaacetic acid (212Bi-DTPA). As expected, 212Bi-DTPA was more effective than X-rays in producing cytotoxicity, chromosome aberrations, and gene mutations. The relative biological effectiveness (RBE) for all three endpoints ranged from about 2 for chromosome aberrations to 4.4 for mutation induction. EM9 was more sensitive than AA8 cells to the cytotoxic and clastogenic effects of both X-rays and 212Bi-DTPA, suggesting that the repair deficiency in EM9 cells affects response to low- and high-linear energy transfer (LET) radiation for these endpoints. There was no significant difference between these two cell lines in their mutagenic response to X-rays and AA8 was slightly more sensitive to the mutagenic effects of alpha radiation. These results suggest that alterations in DNA repair ability may affect response of cells to both low- and high-LET radiation-induced cytotoxicity and clastogenicity, but they appear to have little effect on gene mutation induction. PMID- 2209574 TI - Effect on SCE in human chromosomes in vitro of low-level pulsed magnetic field. AB - We analyzed sister chromatid exchanges (SCE) frequencies as an indicator of DNA damage induced in human lymphocytes in vitro by a low-level pulsed electromagnetic field. We studied the effect of low-level pulsed electromagnetic fields on human chromosomes with the cytogenetic assay of sister chromatid exchange (SCE) analysis. After the human peripheral lymphocyte cultures were exposed in vitro to the electromagnetic field at different intensities, no significant differences were observed when comparing with the control group as to the number of SCE. PMID- 2209575 TI - Mutagenesis assays on urines produced by patients administered adriamycin and cyclophosphamide. AB - The XAD-2 resin concentration/elution system for concentration of mutagens contained in urines was optimized for cancer patients who had been administered such antineoplastic agents as adriamycin (ADR; doxorubicin), cyclophosphamide (CP), methotrexate, vincristine, and 5-fluorouracil. In the reverse mutation assay, Salmonella typhimurium strains TA1535 and TA98 differentiated between CP (with S9 fraction) and ADR (without S9), respectively. No dose-response for CP was observed. There was a dose-response to ADR by TM677 in the presence of S9 using a forward mutation assay. However, while the reverse mutation assays successfully detected ADR and CP administration in the presence of each other in terms of urine mutagenicity, the forward mutation assay did not, since unidentified CP metabolites were also detected in the latter. None of these systems detected mutagenic urines from tobacco smokers, although reaction of these urines with beta-glucuronidase allowed this type of source to be detected also. PMID- 2209576 TI - Comparison of the Salmonella (Ames) test, umu tests, and the SOS Chromotests for detecting genotoxins. AB - The limits of detection of 10 genotoxins representing 7 chemical classes with varying structures and modes of action were compared using the Ames test (Salmonella plate-incorporation test) with 2 tester strains, 2 standard colorimetric methods (the umu test and SOS Chromotest), and modifications of the umu and SOS Chromotests developed during the course of this study. The purpose of the study was to determine the sensitivity and reproducibility of each of the six methods. The sensitivities of the methods were compared using two criteria: the concentrations required for doubling responses, and the minimum concentrations required to produce statistically significant increases from background controls. The Ames test with strains TA98 and TA100 was ranked as the most sensitive method more often than the others, but the results indicated that the umu tests were statistically equivalent to the Ames test. The original SOS Chromotest kit method was highly sensitive in detecting the direct acting genotoxins, but neither SOS test was as sensitive as the other methods in detecting indirect acting genotoxins. The umu microtiter plate test is the least expensive of the assays and would be the most suitable for screening large numbers of environmental samples. PMID- 2209577 TI - Human immunodeficiency virus (HIV) infection in patients with lymphoid neoplasia. AB - Fourty-four patients with lymphoid neoplasia 37 males and 7 females aged 15 to 75 years, were seen in the Department of Internal Medicine, Tikur Anbessa (Black Lion) Hospital, Addis Ababa, Ethiopia, between January and December 1988. Twenty seven (61.4%) had non-Hodgkin's lymphoma, eleven (25%) Hodgkin's disease and six (13.6%) chronic lymphocytic leukaemia. Six (22.2%) of the non-Hodgkin's lymphoma one, (9.1%) of the Hodgkin's disease and none of the chronic lymphocytic leukaemia cases had positive enzyme linked immunosorbent assay (ELISA) and Western Blot tests for human immunodeficiency virus (HIV) infection. Of the 6 non Hodgkin's lymphoma patients with HIV infection, five had extra-nodal involvement- four of the gastrointestinal tract, including the oropharynx, and one of the cervix uteri. Four of these six had clinically advanced disease at the time of presentation and histologically three patients had intermediate and three high grade malignancy. Two of the patients have died within two months of diagnosis, one is lost to follow up, and three patients are still alive and well 12 to 46 months after diagnosis. The HIV positive patient with Hodgkin's disease had stage IV E disease involving the pancreas with mixed cellularity histology, and died seven months after diagnosis. Diffuse, aggressive non-Hodgkin's lymphoma and possibly atypical aggressive Hodgkin's disease, may be indicator diseases for AIDS in HIV seropositive individuals. PMID- 2209578 TI - Ectopic pregnancy at Tikur Anbessa Hospital, Addis Ababa, Ethiopia, 1981-1987: a review of 176 cases. AB - Between September 1981 and August 1987, 242 cases of suspected ectopic pregnancy were admitted to Tikur Anbessa Teaching Hospital, Addis Ababa, Ethiopia, of which 231 were confirmed at laparotomy. Over the same period of time 28,600 deliveries were conducted in the same hospital, giving a ratio of eight ectopic pregnancies to 1,000 deliveries. Review of the 176 cases records which could be retrieved revealed that 57.9% were in the age group of 20-29 years and 27% were nulliparous. The history revealed lower abdominal pain in 98.8%, amenorrhoea in 82.9% and vaginal bleeding in 73%. On clinical examination, 92% had lower abdominal tenderness, 80.6% cervical excitation tenderness, 26.7% a mass in the adnexa and 31.2% a haemoglobin level of 7 gm percent or less. In 51.7% of the cases the ectopic was on the right and in 44.4% on the left. In 37.5% of the cases more than 1,000 millilitres of blood was contained in the peritoneal cavity. Only two were cases of unruptured ectopic pregnancy. There were 5 (2.8%) cornual and 2 (1.1%) ovarian pregnancies. Culdocentesis was the most reliable diagnostic test. In the 176 cases, repeat ectopic occurred in 7.3%. In a situation like ours, where adequate diagnostic facilities are not available, ectopic pregnancy should always be suspected in women with lower abdominal pain and amenorrhoea, or lower abdominal pain and irregular vaginal bleeding. PMID- 2209579 TI - Prevalence of Q fever infection in the Addis Ababa abattoir. AB - A total of 465 human sera were collected for a serological survey of Q fever Infection from the Addis Ababa, Ethiopia, abattoir, in 1988. The subjects' sera were tested for antibodies against Coxiella burnetti antigen using the complement fixation test. Results indicate a prevalence rate of 6.5%. This finding clearly demonstrates serological evidence of post infection with Q fever in employees of the abattoir. PMID- 2209582 TI - Renal haemangioma as a cause of gross haematuria. PMID- 2209580 TI - Community-based study of neurological disorders in Ethiopia: development of a screening instrument. AB - This paper describes the development of a screening instrument for a community based neuroepidemiological survey in a rural community in Ethiopia. A pilot study in 1984 to pre-test the questionnaires developed revealed that epilepsy, poliomyelitis, mental retardation and speech disturbances were the most common neurological disorders among the 3,000 rural inhabitants surveyed. The study suggested that a base-population of about 50,000 was required for a future major epidemiological survey to identify rare neurological disorders. PMID- 2209581 TI - Normal thyroid function values in Ethiopians. AB - Thyroid function values were determined in 56 healthy nongoitrous adult Ethiopians. The mean triiodothyronine (T3) values for 20 males and 36 females were 1.42 +/- 0.32 nmol/L and 1.51 +/- 0.25 nmol/L, and thyroxine (T4) values were 119 22 nmol/L and 116 +/- 21 nmol/L respectively. The mean thyrotropin (TSH) values for males and females were identical at 1.85 +/- 0.94 mu/L. Radioactive iodine uptake (RAIU) at 2 hours was 8.6 +/- 4.4% in males and 11.3 +/- 4.3% in females, and at 24 hours 31.7 +/- 11.7% and 38.9 +/- 11.1% respectively. The differences between males and females were significant at both 2 and 24 hours (P less than 0.05). The ranges for the 3 hormones derived from the mean 2SD values are close to those supplied with the kits but the Ethiopian RAIU values are higher than the values currently applicable in developed countries, probably indicative of the lower level of dietary iodine available to the population here. The values obtained in this study are offered to serve as normal reference for the interpretation of thyroid function results in Ethiopian patients. A strategy for the rational utilization of the available in vivo [corrected] tests is suggested. PMID- 2209583 TI - A case of cryptosporidiosis in a young boy from Addis Ababa. PMID- 2209584 TI - Gunshot injuries of the soft and bony tissues of the face. AB - A classification of wounds into penetrating, avulsive and perforating, applied to the face and neck region is given. The results of the management of 60 patients with gunshot injuries treated in Gondar College of Medical Sciences Hospital in 1987-1988 are evaluated. In all cases there was soft tissue damage associated with comminuted fractures of the facial bones. Primary wound healing was possible in 31 patients. Complicated wound repair was needed in 22 cases. Open wound management with secondary suturing was performed in 4; the other 3 casualties died of brain damage. Differences from the treatment of combat wounds in the extremities are pointed out. All salvageable soft tissue of the face and neck region should be preserved, and methods of intraosseous suturing of fractured facial bones, craniofacial suspension, and compression osteosynthesis can be applied. PMID- 2209585 TI - Heat capacity and entropy changes of troponin C from bullfrog skeletal muscle induced by calcium binding. AB - In order to elucidate the structural changes of bullfrog skeletal muscle troponin C (TnC) caused by Ca2+ binding, microcalorimetric titrations were performed in both the absence and presence of Mg2+, at pH 7.0, and at 5 degrees, 15 degrees, and 25 degrees C. The results indicate that, in the absence of Mg2+, Ca2+ binding to sites 1 and 2 gives rise to a large hydrophobic effect, a sequestering of nonpolar groups on the surface of molecule to the interior, and a tightening of the molecular structure as a whole. In contrast, hydrophobic groups were exposed from the interior to the surface of molecule and the molecular mobility was increased, upon Ca2+ binding to site 3. Ca2+ binding to site 4 induced much less change in the conformation of TnC molecule than that to the other sites. The presence of 5 mM Mg2+ dramatically reduced the magnitude of the conformational changes in TnC on Ca2+ binding to sites 1 and 2. On the other hand, the conformational changes by Ca2+ binding to sites 3 and 4 were not affected by Mg2+. Ca2+ binding to site 3 of TnC, thus, causes the conformational changes distinctly different from those upon Ca2+ binding to the other sites. The conformational changes upon Ca2+ binding to site 3 of TnC are also clearly distinct from the Ca2(+)-induced conformational changes of parvalbumins, but are similar to those of calmodulin. Site 3 of TnC may, therefore, be the regulatory site in muscle contraction, and the exposure or generation of hydrophobic groups on the surface of molecule as well as the increase in molecular mobility may be the common characteristics of the regulation by Ca2(+)-binding proteins. PMID- 2209586 TI - Primary structure of sorghum malate dehydrogenase (NADP) deduced from cDNA sequence. Homology with malate dehydrogenase (NAD). AB - Malate dehydrogenase (NADP) (NADP-MDH) is an important enzyme of the photosynthetic CO2 fixation pathway of C4 plants. We have isolated two clones from a sorghum lambda gt11 cDNA library (CM3, 932 bp, and CM7, 1441 bp). Nucleotide sequence analysis of the cDNAs CM3 and CM7 showed the existence of two NADP-MDH mRNA species encoding different enzyme subunits. Microsequencing of the N-terminus of the mature protein indicated that a specific cleavage of 13 amino acids occurred during the purification steps of the enzyme. The full-length cDNA CM7 contains a large open reading frame encoding an NH2-terminal transit peptide of 40 amino acids and a mature protein of 389 amino acids (42.207 kDa). Alignment of the NADP-MDH sequence with those of several malate dehydrogenases revealed some similarities with NAD-MDHs. PMID- 2209588 TI - Transcription factor TFIIIA stimulates DNA supercoiling promoted by a fractionated cell-free extract from Xenopus laevis. AB - An activity that can introduce negative supercoils into relaxed covalently closed DNA molecules has been isolated from a Xenopus laevis cell-free extract (S-150) and purified over 200-fold. The exogenous addition of ATP, other ribonucleotides and deoxyribonucleotides, as well as nonhydrolyzable analogs, stimulate DNA supercoiling which may occur by a pathway involving multiple protein components. DNA supercoiling occurs in topological single steps and is inhibited by camptothecin and berenil, but not novobiocin or VM-26, suggesting a catalytic role for topoisomerase I in the reaction. Transcription factor TFIIIA stimulates DNA supercoiling catalyzed by the isolated fraction at low factor to DNA ratios. Taken together, these results suggest that a isolated DNA supercoiling activity from the X. laevis S-150 cell-free extract can be stimulated by transcription factor TFIIIA. PMID- 2209587 TI - Fluoroaluminates do not affect the guanine-nucleotide binding centre of the peptide chain elongation factor EF-Tu. AB - EF-Tu is often referred to as a model for guanine-nucleotide-binding regulatory proteins (G-proteins), since X-ray diffraction analysis of its GTP-binding domain shows a detailed location of the 'consensus' amino acid sequences involved in nucleotide binding. Fluoroaluminates are thought to mimick the gamma-phosphate in the GTPase centre on account of their activating effect on a variety of GTP binding proteins. In the case of EF-Tu, we could find no such effects on the basis of at least three independent functional assays. We did notice, however, complicating interactions between free nucleotides, fluoroaluminates and other ligands. By consequence, if indeed AlF4- behaves as a gamma-phosphate analogue in G-proteins, then EF-Tu must have a different GDP/GTP binding site, despite of the conserved consensus sequences. PMID- 2209589 TI - Sequence-specific 1H-NMR assignment and conformation of proteolytic fragment 163 231 of bacterioopsin. AB - Proteolytic fragment 163-231 of bacterioopsin was isolated from Halobacterium halobium purple membrane treated with NaBH4 and papain under nondenaturing conditions. Two-dimensional 1H-NMR spectra of (163-231)-bacterioopsin solubilized in chloroform/methanol (1:1), 0.1 M LiClO4 indicated the existence of one predominant conformation. Most of the resonances in the 1H-NMR spectra of (163 231)-bacterioopsin were assigned by two-dimensional techniques. Two extended right-handed alpha-helical regions Ala168-Ile191 and Asn202-Arg227 were identified on the basis of NOE connectivities and deuterium exchange rates. The N terminal part of the peptide is flexible and the region of Gly192-Leu201 adopts a specific conformation. The protons of OH groups of Thr178, Ser183 and Ser214 slowly exchange with solvent, and side-chain conformations of these residues, as evaluated by NOE connectivities of OH protons, are optimal for the formation of hydrogen bonds between OH and backbone carbonyl groups. PMID- 2209590 TI - A novel tubulin from Mimosa pudica. Purification and characterization. AB - From Mimosa pudica fresh leaves and pulvinar callus cells, we have purified tubulin protein using an anion-exchange resin, DEAE-Sephadex A-50, followed by ammonium sulfate fractionation and Sephadex G-200 gel filtration. The purified protein consisted of alpha and beta subunits and trace quantities of other proteins. When analysed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis at pH 8.8, both alpha and beta subunits of tubulin almost comigrated with their counterparts from goat brain. Two-dimensional electrophoresis revealed that this tubulin contains one major alpha-tubulin having a pI value of 7.1 and three beta species having pI values of 6.70, 6.46 and 6.40. Morphologically normal microtubules were observed by electron microscopy; self-polymerization in vitro, even in the cold, can also be achieved. Radioimmunoassays, and also immunoblotting with the antibodies raised against alpha- and beta-tubulins of this plant, showed that the nature of alpha-tubulin is different from that obtained from other sources. This is an example of plant tubulin where strong colchicine binding at 1 microM was observed. This protein constitutes 5-6% of the total extractable protein in the leaves. We propose that movement of the leaves of this plant may be regulated by the presence of a high amount of this protein. PMID- 2209592 TI - Control analysis of systems having two steps catalyzed by the same protein molecule in unbranched chains. AB - The analysis of the control of a metabolic pathway having an enzyme catalyzing two different reactions (or a protein displaying two different activities) has been performed. For such systems although the summation theorems are valid, the flux and concentration connectivity theorems of the metabolic control analysis are not valid. Another general relationship of control analysis is shown to be more widely obeyed and holds in these systems. An exemplary case, where the enzyme catalyzes two irreversible reactions, demonstrates that the level of one internal intermediate is constant, i.e. it does not depend upon the independent variables of the system. PMID- 2209591 TI - Control of respiration and oxidative phosphorylation in isolated rat liver cells. AB - NAD(P)H fluorescence, mitochondrial membrane potential and respiration rate were measured and manipulated in isolated liver cells from fed and starved rats in order to characterize control of mitochondrial respiration and phosphorylation. Increased mitochondrial NADH supply stimulated respiration and this accounted for most of the stimulation of respiration by vasopressin and extracellular ATP. From the response of respiration to NADH it was estimated that the control coefficient over respiration of the processes that supply mitochondrial NADH was about 0.15 0.3 in cells from fed rats. Inhibition of the ATP synthase with oligomycin increased the mitochondrial membrane potential and decreased respiration in cells from fed rats, while the uncoupler carbonyl cyanide p trifluoromethoxyphenylhydrazone had the opposite effect. There was a unique relationship between respiration and membrane potential irrespective of the ATP content of the cells indicating that phosphorylation potential controls respiration solely via phosphorylation (rather than by controlling NADH supply). From the response of respiration to the mitochondrial membrane potential (delta psi M) it was estimated that the control coefficients over respiration rate in cells from fed rats were: 0.29 by the processes that generate delta psi M, 0.49 by the process of ATP synthesis, transport and consumption, and 0.22 by the processes that cycle protons across the inner mitochondrial membrane other than via ATP synthesis (e.g. the passive proton leak). Control coefficients over the rate of mitochondrial ATP synthesis were 0.23, 0.84 and -0.07, respectively, by the same processes. The control distribution in cells from starved rats was similar. PMID- 2209593 TI - Amino acid sequences of four isoforms of amphioxus sarcoplasmic calcium-binding proteins. AB - The protochordate amphioxus (Branchiostoma lanceolatum) contains different isoforms of sarcoplasmic, high-affinity Ca2(+)-binding proteins (SCP). The amino acid sequences of the two major isoforms SCP I and II, reported previously [Takagi, T., Konishi, K. & Cox, J.A. (1986) Biochemistry 25, 3585-3592], have been corrected and differ from each other by seven amino acid substitutions in a 17-residue-long segment (positions 20-36). We also report on the isolation and amino acid sequence determination of two minor isoforms, i.e. amphioxus SCP III and IV. Although they behave very differently from the major forms with respect to net charge, they differ from SCP I by only one amino acid: SCP III has Met at position 20 (Tyr in SCP I) and SCP IV has Asn at position 23 (Asp in SCP I). Together the sequence data on amphioxus SCP suggest that, in contrast with SCP of other invertebrate phyla, the isoforms are generated by alternative splicing of the primary RNA transcript with a mutually exclusive pattern. PMID- 2209594 TI - On the roles of magnesium and spermidine in the isoleucyl-tRNA synthetase reaction. Analysis of the reaction mechanism by total rate equations. AB - The reaction of isoleucyl-tRNA synthetase from Escherichia coli B was analysed by deriving total steady-state rate equations for the ATP/PPi exchange reaction and for the aminoacylation of tRNA, and by fitting these rate equations to series of experimental results. The analysis suggests that (a) a Mg2+ inhibits the aminoacylation of tRNA but not the activation of the amino acid. In the chosen mechanism, this enzyme-bound Mg2+ is required at the activation step. (b) Another Mg2+ is required at ATP, but the MgATP apparently can be replaced by the spermidine.ATP complex. Spermidine.ATP is a weaker substrate. The role of spermidine.ATP is especially suggested by the relative rates of the aminoacylation of tRNA when the spermidine and magnesium concentrations are varied. The aminoacylation measurements still suggest that (c) two (or more) Mg2+ are bound to the tRNA molecule and are required for enzyme activity at the transfer step, and that these Mg2+ can be replaced by spermidines. PMID- 2209595 TI - Purification and properties of a NADH-dependent 5,10-methylenetetrahydrofolate reductase from Peptostreptococcus productus. AB - The methylenetetrahydrofolate reductase from the carbon-monoxide-utilizing homoacetogen Peptostreptococcus productus (strain Marburg) has been purified to apparent homogeneity. The purified enzyme catalyzed the oxidation of NADH with methylenetetrahydrofolate as the electron acceptor at a specific activity of 380 mumols.min-1 mg protein-1 (37 degrees C; pH 5.5). The apparent Km for NADH was near 10 microM. The apparent molecular mass of the enzyme was determined by gel filtration to be approximately 250.0 kDa. The enzyme consists of eight identical subunits with a molecular mass of 32 kDa. It contains 4 FAD/mol octamer which were reduced by the enzyme with NADH as the electron donor; iron could not be detected. Oxygen had no effect on the enzyme. Ultracentrifugation of cell extracts revealed that about 40% of the enzyme activity was recovered in the particulate fraction, suggesting that the enzyme is associated with the membrane. The enzyme also catalyzed the methylenetetrahydrofolate reduction with methylene blue as an artificial electron donor. The oxidation of methyltetrahydrofolate was mediated with methylene blue as the electron acceptor; neither NAD+ nor viologen dyes could replace methylene blue in this reaction. NADP(H) or FAD(H2) were not used to substrates for the reaction in either direction. The activity of the purified enzyme, which was proposed to be involved in sodium translocation across the cytoplasmic membrane, was not affected by the absence or presence of added sodium. The properties of the enzyme differ from those of the ferredoxin dependent methylenetetrahydrofolate reductase of the homoacetogen Clostridium formicoaceticum and of the NADP(+)-dependent reductase of eucaryotes investigated so far. PMID- 2209596 TI - Hepatic processing and biliary secretion of the cholesteryl esters from beta very low-density lipoproteins in the rat. AB - beta-Migrating very-low-density lipoproteins (beta-VLDL) are cholesteryl-ester enriched lipoproteins which accumulate in the serum of cholesterol-fed animals or patients with type III hyperlipoproteinemia. In the rat, beta-VLDL are rapidly cleared by the liver and parenchymal liver cells form the major site for uptake. In this investigation, beta-VLDL were labeled with [3H]cholesteryl esters and the hepatic intracellular transport of these esters was followed. 2 min after injection, the major part of the [3H]cholesteryl esters is already associated with the liver and a significant proportion is recovered in endosomes. Up to 25 min after injection, an increase in radioactivity in the lysosomal compartment is noticed. This radioactivity initially represents cholesteryl esters, while from 25 min onward, radioactivity is mainly present in unesterified cholesterol. Between 45 min and 90 min after beta-VLDL injection, specific transfer of unesterified [3H]cholesterol to the endoplasmic reticulum is observed, while by 3 h the majority is located in this fraction. The appearance of radioactivity in the bile was rather slow as compared to the rapid initial uptake and processing, and up to 5 h after injection only 10% of the injected dose had reached the bile (mainly as bile acids). 72 h after injection, the amount of the injected radioactivity recovered in the bile had increased to 50%. Chloroquine treatment of the rats inhibited the hydrolysis of the cholesteryl esters and the appearance of radioactivity in the bile was retarded. It is concluded that beta-VLDL are rapidly processed by parenchymal liver cells and that the cholesteryl esters from beta-VLDL are hydrolyzed in the lysosomal compartment. Unesterified cholesterol remains associated with the endoplasmic reticulum for a prolonged time, although ultimately the majority will be secreted into the bile as bile acids. The effective operation of this pathway will prevent extrahepatic accumulation of cholesteryl esters from beta-VLDL, while the prolonged residence time of unesterified cholesterol in the endoplasmic reticulum might be important for regulation of low-density lipoprotein (LDL) receptors in liver and thus for LDL levels in the blood. PMID- 2209597 TI - Structure determination of five sialylated trisaccharides with core types 1, 3 or 5 isolated from bovine submaxillary mucin. AB - In this study we have investigated the structures of five sialylated trisaccharides released from bovine submaxillary mucin by alkaline borohydride treatment and isolated by high-performance liquid chromatography. Three of the trisaccharides contained NeuAc while two contained NeuGc. One oligosaccharide contained core-type 1, two contained core-type 3 and two contained core-type 5. The structures, determined by a combination of one- and two-dimensional 1H-NMR spectroscopy at 270 MHz and methylation analysis involving gas-liquid chromatography/mass spectrometry, were as follows: A4b, GalNAc alpha(1----3) [NeuAc alpha(2----6)]GalNAcol; A4c, GlcNAc beta(1----3)[NeuAc alpha(2--- 6)]GalNAcol; A4d, Gal beta(1----3)[NeuAc alpha(2----6)]GalNAcol; A4e, GalNAc alpha(1----3)-[NeuGc alpha(2----6)]GalNAcol; A4f, GlcNAc beta(1----3)[NeuGc alpha (2----6)]GalNAcol. The oligosaccharides occurred in the approximate molar ratios 1.0:12.0:0.3:0.2:2.0. This is the first report of oligosaccharides containing core-type 5 and of the occurrence of oligosaccharides A4b, A4e, and A4f in bovine submaxillary mucin. 1H-NMR data for structure A4e, which is a novel structure, are presented for the first time. PMID- 2209598 TI - Conformational preferences of [Leu5]enkephalin in biomimetic media. Investigation by 1H NMR. AB - The conformation of [Leu5]enkephalin has been studied by 1H-NMR spectroscopy in media more like the actual environment in which the agonist-receptor interaction takes place than water, i.e. in three cryoprotective mixtures (dimethylformamide/water, methanol/water and ethylene glycol/water), in aqueous SDS and in two neat solvents, dimethylformamide and acetonitrile, whose dielectric constants (36.7 and 37.5) are intermediate between that of water and that of the lipid phase. In all cases examined, contrary to the studies in water or dimethylsulfoxide, we were able to detect numerous nuclear Overhauser effects, indicating that the media employed favour well-defined structures and/or reduce the internal motions of the peptide. Data from both organic solvents and cryoprotective mixtures suggest a 4----1 beta turn as the most probable structure of [Leu5]enkephalin in solution, whereas in SDS/H2O micelles the structural picture appears completely different, suggesting the presence of a 5----2 beta turn. The existence of two different preferred conformations of enkephalins may possibly be related to their ability to be effective towards both mu and delta opioid receptors. PMID- 2209599 TI - Sequence of proton abstraction and stereochemistry of the reaction catalyzed by naphthoate synthase, an enzyme involved in menaquinone (vitamin K2) biosynthesis. AB - The enzymic conversion of the coenzyme A ester of 4-(2'-carboxyphenyl)-4 oxobutyric acid (i.e. o-succinylbenzoic acid) to 1,4-dihydroxy-2-naphthoic acid is a cyclization reaction which is part of menaquinone (vitamin K2) biosynthesis. This conversion, which is probably a two-step process, was investigated using chirally labelled samples of the coenzyme A ester of 4-(2'-carboxyphenyl)-4 oxobutyric acid. To synthesize these, the following enzymes were employed: isocitrate: NADP+ oxidoreductase (EC 1.1.1.42), isocitrate glyoxylate-lyase (EC 4.1.3.1), 2-oxoglutarate dehydrogenase complex (which includes EC 1.2.4.2), 4-(2' carboxyphenyl)-4-oxobutyrate synthase system and 4-(2'-carboxyphenyl)-4 oxobutyrate: CoA ligase. Isocitrate: NADP+ oxidoreductase was employed to generate the two enantiomeric samples of 2-oxoglutarate enantiotopically labelled at C-3. These samples were converted enzymically to succinate with retention of configuration at C-2 and C-3, and to 4-(2'-carboxyphenyl)-4-oxobutyric acid with retention of configuration at C-3. Isocitrate glyoxylate-lyase and isocitrate NADP+ oxidoreductase were employed to generate samples of 2-oxoglutarate enantiotopically tritiated at C-4 or at C-3 and C-4. The four variously labelled samples of 2-oxoglutarate were enzymically converted to the coenzyme A ester of 4 (2'-carboxyphenyl)-4-oxobutyric acid. The resulting variously labelled coenzyme A esters were incubated with naphthoate synthase to investigate the ring closure reaction. In the first step the 2HRe atom of the oxobutyric moiety of the coenzyme A ester is equilibrated with solvent protons in a fast and reversible reaction. Subsequently the 2HSi and 3HSi atoms are removed whereas the 3HRe atom becomes the proton at C-3 of 1,4-dihydroxy-2-naphthoic acid. The second step in this ring closure reaction is the rate-limiting step. PMID- 2209601 TI - Inhibition of inositol 1,4,5-trisphosphate metabolism in permeabilised SH-SY5Y human neuroblastoma cells by a phosphorothioate-containing analogue of inositol 1,4,5-trisphosphate. AB - Electrically permeabilised [3H]inositol-labelled SH-SY5Y human neuroblastoma cells were employed to examine the effects of two synthetic, phosphatase resistant analogues of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] on the metabolism of cell membrane-derived [3H]Ins(1,4,5)P3 or exogenous [5 32P]Ins(1,4,4)P3. Incubation of permeabilised SH-SY5Y cells for 5 min at 37 degrees C with carbachol and guanosine 5'-[gamma-thio]triphosphate caused a decrease in [3H]phosphoinositol phospholipid levels and an increase in [3H]inositol phosphate accumulation with inositol 4-phosphate, inositol 1,4 bisphosphate, Ins(1,4,5)P3 and inositol 1,3,4,5-tetrakisphosphate comprising approximately 79%, 16%, 3% and 2%, respectively, of the increase. Inositol 1 phosphate levels did not increase upon stimulation, nor was inositol 4-phosphate converted rapidly to inositol. In parallel incubations, the analogues, DL inositol 1,4,5-trisphosphorothioate (DL-InsP3S3) and DL-inositol 1,4-bisphosphate 5-phosphorothioate (DL-InsP3S), and synthetic racemic Ins(1,4,5)P3 (DL-InsP3), altered the profile of the [3H]inositol phosphates recovered and led, at millimolar concentrations, to a 10-15-fold increase in [3H]Ins(1,4,5)P3. The extent of inhibition of [3H]Ins(1,4,5)P3 metabolism was, however, greatest in the presence of synthetic D-Ins(1,4,5)P3 (greater than or equal to 5 mM), when [3H]Ins(1,4,5)P3 comprised approximately 50% of the increase in total [3H]inositol phosphates. Thus, under these conditions, at least 50% of [3H]inositol phosphates were derived from [3H]phosphatidylinositol 4,5 bisphosphate. [32P]Pi release from exogenous [5-32P]Ins(1,4,5)P3 was also inhibited by DL-InsP3S3, DL-InsP3S and DL-InsP3, with half-maximal inhibition at approximately 50 microM, 160 microM and 240 microM respectively. These actions were approximately ten times more potent than the effects of these compounds on [3H]inositol phosphate accumulation, indicating that homogenous mixing of exogenous and cell-membrane-derived Ins(1,4,5)P3 does not occur. These findings indicate that DL-InsP3S3 and DL-InsP3S inhibit Ins(1,4,5)P3 5-phosphatase. In contrast, the effects of synthetic DL-InsP3 and D-Ins(1,4,5)P3 are due to isotopic dilution. Whilst DL-InsP3S3 was the most potent inhibitor of dephosphorylation of exogenous or cell-membrane-derived Ins(1,4,5)P3, it was the weakest inhibitor of 3-kinase-catalysed Ins(1,4,5)P3 phosphorylation. Similarly, although approximately 50 times less potent than DL-InsP3S3, 2,3 diphosphoglycerate inhibited Ins(1,4,5)P3 5-phosphatase activity and was apparently without effect of Ins(1,4,5)P3 3-kinase activity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2209600 TI - Expression and characterization of the chick nicotinic acetylcholine receptor alpha-subunit in insect cells using a baculovirus vector. AB - A baculovirus transfer vector was constructed containing an entire cDNA copy of the chick nicotinic acetylcholine receptor (nAChR) alpha-subunit under control of the Autographa californica nuclear polyhedrosis virus (AcNPV) polyhedrin gene promoter. Recombinant baculovirus was obtained by co-transfection of Spodoptera frugiperda cells with infectious, wild-type AcNPV DNA and the transfer vector. Polyhedrin-negative, recombinant viruses were identified which expressed the nAChR alpha-subunit. The insect cell-expressed alpha-subunit protein had a molecular mass of 42 kDa and was shown to be targeted to the plasma membrane by fluorescence microscopy and toxin-binding assays. The levels of expression were low, approximately 1-2% of cell proteins, when compared with the levels of natural polyhedrin protein. The expressed receptor alpha-subunit was recognised by polyclonal antisera raised against purified Torpedo nAChR alpha-subunit and carried the binding site for the snake venom toxin, alpha-bungarotoxin. Bound alpha-bungarotoxin was displaced in competition binding assays by alpha-cobra toxin, carbamylcholine and d-tubocurarine, and thus had a similar pharmacological profile to that obtained with authentic receptors in muscle cells and receptors expressed in other systems i.e. Xenopus oocytes and mammalian cells. We have also shown that when the chick nAChR alpha-subunit is expressed in the absence of other receptor subunits, unexpectedly high concentrations of nicotine (10 mM) were required to displace bound alpha-bungarotoxin. PMID- 2209602 TI - Internalization of the cytotoxic molecules of T101 F(ab')2-(ricin-A-chain) immunotoxin into human T-leukemic cells. AB - We have investigated the internalization step of an immunotoxin and its relationship with cytotoxicity, with the F(ab')2-T101(ricin-A-chain) immunotoxin, directed against the CD5 antigen expressed on leukemic CEM cells. We first demonstrated that the biological action of the conjugate was related to its entry into the cell by an energy-dependent endocytotic process. We also found that during the first hours of cell intoxication, internalization is not the rate limiting step of immunotoxin cytotoxicity. Internalization becomes limiting in cell intoxication only when the entry rate is low. Lastly we show that ammonium chloride, which strongly enhances immunotoxin potency, acts on internalized molecules for a very short time, suggesting that this enhancer affects an early intracellular step. PMID- 2209603 TI - Plasma membrane Fe2-transferrin reductase and iron uptake in K562 cells are not directly related. AB - Receptor-mediated endocytosis and recycling of transferrin is partly inhibited by the ferrous iron chelator bipyridine, which almost completely blocks iron uptake. Bipyridine causes iron release at the cell surface, but inhibition of iron uptake is also due to a blockage of its passage through the endosomal membrane. The rate of release of iron to bipyridine is decreased by the competing electron acceptor ferricyanide and by amiloride, but not by iron uptake inhibiting acidotropic amines. Transferrin reduction at the plasma membrane may be artificially induced by presence of a ferrous chelator and caused by low-affinity transmembrane NAD(P)H oxidoreductase. PMID- 2209604 TI - An anti-inflammatory protein secreted from the rat seminal vesicle epithelium inhibits the synthesis of platelet-activating factor and the release of arachidonic acid and prostacyclin. AB - Platelet-activating factor (PAF), a 1-O-alkyl-2-acetyl-sn-glycero-3 phosphocholine, is a mediator of inflammation and endotoxic shock produced by a variety of stimulated cells. Since the main biosynthetic pathway of PAF involves acetylation of 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) generated from 1 O-alkyl-2-acyl-sn-glycero-3-phosphocholine by phospholipase A2, we suggest a general physiological role played by steroid-induced anti-(phospholipase A2) proteins in the modulation of PAF synthesis. The results of the present study support this hypothesis since an androgen-induced anti-inflammatory protein, SV IV, secreted from rat seminal vesicles, inhibits PAF synthesis in stimulated polymorphonuclear neutrophils, macrophages and endothelial cells. SV-IV impairs PAF synthesis by inhibiting the activation of phospholipase A2, that also results in the inhibition of arachidonic acid and prostacyclin release, and of acetyl CoA:lyso-PAF acetyltransferase. PMID- 2209605 TI - The multifunctional 6-methylsalicylic acid synthase gene of Penicillium patulum. Its gene structure relative to that of other polyketide synthases. AB - 6-Methylsalicylic acid synthase (MSAS) from Penicillium patulum is a homomultimer of a single, multifunctional protein subunit. The enzyme is induced, at the transcriptional level, during the end of the logarithmic growth phase. After approximately 150-fold purification, a homogeneous enzyme preparation was obtained exhibiting, upon SDS gel electrophoresis, a subunit molecular mass of 188 kDa. By immunological screening of a genomic P. patulum DNA expression library, the MSAS gene together with its flanking sequences was isolated; 7131 base pairs of the cloned genomic DNA were sequenced. Within this sequence the MSAS gene was identified as a 5322-bp-long open reading frame coding for a protein of 1774 amino acids and 190,731 Da molecular mass. Transcriptional initiation and termination sites were determined both by primer extension studies and from cDNA sequences specially prepared for the 5' and 3' portions of the gene. The same cDNA sequences revealed the presence of a 69-bp intron within the N-terminal part of the MSAS gene. The intron contains the canonical GT and AG dinucleotides at its 5'- and 3'-splice junctions. An internal TACTGAC sequence, resembling the TACTAAC consensus element of Saccharomyces cerevisiae introns is suggested to represent the branch point of the lariat splicing intermediate. When compared to other known polyketide synthases, distinct amino acid sequence similarities of limited lengths were observed with some, though not all, of them. A comparatively low degree of similarity was detected to the yeast and Penicillium FAS or to the plant chalcone and resveratrol synthases. In contrast, a significantly higher sequence similarity was found between MSAS and the rat fatty acid synthase, especially at their transacylase, 2-oxoacyl reductase, 2 oxoacyl synthase and acyl carrier protein domains. Besides several dissimilar, interspersed regions probably coding for MSAS- and FAS-specific functions, the sequential order of the similar domains was colinear in both enzymes. The low similarity between the two P. patulum polyketide synthases, MSAS and FAS, possibly supports a convergent rather than a divergent evolution of both multienzyme proteins. PMID- 2209607 TI - The bovine plasma retinol-binding protein. Amino acid sequence, interaction with transthyretin, crystallization and preliminary X-ray data. AB - 1. The primary structure of bovine plasma retinol-binding protein (RBP) has been determined and found to be more than 90% identical to human and rabbit RBPs, and more than 80% identical to rat RBP. Main changes in amino acid sequence are observed in two regions on the surface of the protein molecule (residues 138-148 and 169-183). 2. The interactions of bovine RBP with bovine and human transthyretins were investigated using the technique of fluorescence polarization. Bovine RBP was able to form high affinity complexes (K'd = 0.34 +/- 0.02 microM) with both bovine and human transthyretins, displaying a stoichiometry of approximately 2 molecules RBP/molecule transthyretin in both cases. The sites that participate in protein-protein interactions are thus very similar, and this tends to exclude the involvement of the superficial regions more significantly substituted in mammalian RBPs (residues 138-151 and 167-183) in the protein-protein recognition. 3. Bovine RBP has been crystallized (space group P2(1)2(1)2(1), with a = 4.61 nm, b = 4.91 nm, c = 7.61 nm) and the crystals are suitable for high-resolution X-ray diffraction studies. PMID- 2209606 TI - Regulated expression and phosphorylation of the 23-26-kDa ras protein in the sponge Geodia cydonium. AB - We have cloned, sequenced and examined the sponge Geodia cydonium cDNA encoding a protein homologous to ras proteins. The sponge ras protein has a more conserved N terminal region and a less conserved C-terminal region, especially in comparison to Dictyostelium discoideum; the similarity to human c-Ha-ras-1 and to Saccharomyces cerevisiae is less pronounced. The sponge ras cDNA comprises five TAG triplets; at the translational level these UAG termination codons are suppressed by a Gln-tRNA. The sponge ras protein was isolated and partially purified (23-26 kDa) and found to undergo phosphorylation at a threonine moiety, when dissociated cells were incubated in the presence of a homologous aggregation factor and insulin. Insulin-mediated phosphorylation of the ras protein resulted in a decrease in its Kd with GTP from 2 microM to 80 nM. The activated ras protein displayed high GTPase activity if the partially purified protein was incubated with homologous lectin and lectin receptor molecules. These results suggest that in the sponge, ras is activated by the insulin/insulin(insulin-like) receptor system. This transition enables the ras protein to interact with the lectin-receptor/lectin complex, a process which may ultimately lead to an initiation of an intracellular signal-transduction chain. PMID- 2209609 TI - The spectrum of N-linked oligosaccharide structures detected by enzymic microsequencing on a recombinant soluble CD4 glycoprotein from Chinese hamster ovary cells. AB - Structures of the N-linked oligosaccharides of a recombinant soluble form of human CD4 glycoprotein (sCD4) have been investigated by enzymic microsequencing. The glycoprotein has two N-glycosylation sites, Asn271 and Asn300, at both of which evidence for the presence of complex type biantennary sialo oligosaccharides has been obtained previously by mass spectrometric analyses [Carr, S.A., Hemling, M.E., Folena-Wasserman, G., Sweet, R.W., Anumula, K., Barr, J.R., Huddleston, M.J. & Taylor, P. (1989) J. Biol. Chem. 264, 21,286-21,295]. Among oligosaccharides released from sCD4 by hydrazinolysis and labelled with NaB3H4, neutral (12.8%) and acidic (87.2%) oligosaccharides were detected by paper electrophoresis. The latter were rendered neutral following sialidase treatment indicating that acidity was due exclusively to the presence of sialic acid residues. By enzymic microsequencing of the sialidase-treated oligosaccharides (fractionated on affinity columns of Ricinis communis agglutinin 120 and concanavalin A) in conjunction with methylation data from the earlier study, 14 sequences were identified. These accounted for over 80% of the sialidase-treated oligosaccharides of sCD4 as follows: [formula: see text] where +/- indicates residues present on only a proportion of chains. The spectrum of oligosaccharide structures released from each glycosylation site was assessed as being similar to that of total oligosaccharides on the basis of their chromatographic profiles on the lectin columns and on Bio-Gel P-4. PMID- 2209608 TI - Primary structure of the bovine analogues to human apolipoproteins CII and CIII. Studies on isoforms and evidence for proteolytic processing. AB - Two major isoforms of the bovine analogue to human apolipoprotein (apo) CII were purified from plasma. They were both as effective as human apo CII in activating lipoprotein lipase. Amino acid sequencing revealed that one form contained 79 amino acid residues, and corresponded to human pro apo CII. The other form lacked the first six residues at its N-terminus. This was apparently due to cleavage of the -Gln-Asp- linkage in the sequence H2N-Ala-His-Val-Pro-Gln-Gln-Asp-Glu-, analogous to cleavages described for human apo AI and apo CII. Previous studies with human apo CII have shown that the ability to activate lipoprotein lipase resides in the C-terminal third of the molecule. This was highly conserved in the bovine analogue: of the 30 last residues, 21 are identical. Five residues in this part of human apo CII have been reported to be essential for activation of lipoprotein lipase. Only one of these, Tyr63, is present in the bovine sequence. The bovine structure contains a threonine at position 61, instead of serine in the human, and the four last residues are -Ser-Gly-Lys-Asp instead of the allegedly necessary -Lys-Gly-Glu-Glu. Three differently sialylated isoforms of the bovine analogue to human apolipoprotein CIII were also isolated and partially sequenced. All three lacked the first three N-terminal residues as compared to sequences from other species (man, dog and rat). Sequence differences were more pronounced at the ends than in the central parts of the apo CIII molecules. PMID- 2209611 TI - Techniques in plant molecular biology--progress and problems. AB - Progress in plant molecular biology has been dependent on efficient methods of introducing foreign DNA into plant cells. Gene transfer into plant cells can be achieved by either direct uptake of DNA or the natural process of gene transfer carried out by the soil bacterium Agrobacterium. Versatile gene-transfer vectors have been developed for use with Agrobacterium and more recently vectors based on the genomes of plant viruses have become available. Using this technology the expression of foreign DNA, the functional analysis of plant DNA sequences, the investigation of the mechanism of viral DNA replication and cell to cell spread, as well as the study of transposition, can be carried out. In addition, the versatility of the gene-transfer vectors is such that they may be used to isolate genes not amenable to isolation using conventional protocols. This review concentrates on these aspects of plant molecular biology and discusses the limitations of the experimental systems that are currently available. PMID- 2209610 TI - Stimulation of Ca2+ uptake into epididymal bull spermatozoa by analogues of amiloride. AB - Certain amiloride analogues 3',4'-dichlorobenzamil 2',4'-dimethylbenzamil and alpha',2'-benzobenzamil hydrochloride (ATBB) stimulate calcium accumulation and motility by epididymal bovine spermatozoa. This stimulation can be seen at a range of 0.1-0.4 mM, while at higher concentration there is inhibition of calcium uptake by these amiloride analogues. The amiloride derivative 5-(4-chlorobenzyl) 2',4'-dimethylbenzamil (CBDMB), which bears a 4-chlorobenzyl substituent on the 5 amino nitrogen atom, did not stimulate calcium uptake. The amiloride analogue 3',4'-dichlorobenzamil inhibits the Na+/Ca2(+)-exchange activity in isolated plasma membrane vesicles, and the stimulatory effect of 3',4'-dichlorobenzamil on calcium uptake into epididymal sperm could be seen in Na(+)-free medium. Thus, the stimulation of Ca2+ accumulation in the cells caused by 3',4' dichlorobenzamil is not a result of inhibiting the Na(+)-dependent Ca2+ clearance. There is no stimulation of Ca2+ uptake into ejaculated cells by adding 3',4'-dichlorobenzamil, which is not due to the presence of the calcium-transport inhibitor (caltrin) in these cells [Rufo, G.A., Schoff, P.K. & Lardy, H.A. (1984) J. Biol. Chem. 259, 2547-2552]. The stimulatory effect of 3',4'-dichlorobenzamil on Ca2+ uptake is inhibited by the voltage-dependent Ca2(+)-channel blockers nifedipin and diltiazem. This indicates that the stimulation of Ca2+ uptake by the amiloride analogues is due to the activation of a voltage-dependent Ca2+ channel of the plasma membrane. PMID- 2209612 TI - Regulation of heme oxygenase gene expression by cobalt in rat liver and kidney. AB - The effect of heavy metals such as cobalt chloride and the corresponding metalloporphyrin on the transcription of the heme oxygenase gene in tissues was examined using cDNA for rat heme oxygenase as the probe. An increase in heme oxygenase mRNA level was observed in response to cobalt chloride and cobalt protoporphyrin treatment in both liver and kidney. Quantitative evaluation of the heme oxygenase transcript was obtained by determining the intensity of mRNA bands by scanning densitometry, and indicated that cobalt chloride increased heme oxygenase mRNA by 40-60-fold after 2 h of metal exposure. Accumulation of heme oxygenase mRNA after cobalt chloride administration was prevented by co administration of actinomycin D or cycloheximide. These results indicate that the increased expression of heme oxygenase by cobalt chloride required de novo protein synthesis and was regulated at the transcriptional level. The time course of heme oxygenase transcript accumulation following administration of cobalt protoporphyrin was different from that of cobalt chloride. There was a sharp increase in heme oxygenase mRNA after cobalt chloride administration at 2 h and cobalt protoporphyrin at 10 h. Heme, to which cobalt protoporphyrin is structurally analogous, acted as a potent inducer of heme oxygenase transcripts in both liver and kidney. Variation in heme oxygenase mRNA levels resulting from enhanced transcription of the heme oxygenase gene was evaluated by nuclear runoff assay using isolated rat liver nuclei after cobalt chloride administration. Quantification of specific nuclear RNAs labeled during the in vitro transcription revealed active heme oxygenase gene transcription in liver nuclei from cobalt chloride-treated rats. Transcription of heme oxygenase is greatly increased within 1 h of administration of cobalt chloride in rat liver, as evidenced by the level of [alpha-32P]UTP incorporation into nuclear RNA. The transcription was increased by 40-fold after 3 h of cobalt chloride administration. The activation of the heme oxygenase gene by metal ions is the most rapid transcriptional response to heavy metals yet described and highlights the regulatory role of heme oxygenase in heme degradation during deviating environmental conditions. On the other hand, cobalt protoporphyrin and heme arginate increase transcription of the heme oxygenase gene in a similar pattern but at a slower rate than that of the heavy metal, suggesting that the heme oxygenase promotor region may contain additional elements conferring the inducing effect of these two agents. PMID- 2209613 TI - Conformational transitions within the head and at the head-rod junction in smooth muscle myosin studied with a limited proteolysis method. AB - It was previously shown that tryptic digestion of subfragment 1 (S1) of skeletal muscle myosins at 0 degree C results in cleavage of the heavy chain at a specific site located 5 kDa from the NH2-terminus. This cleavage is enhanced by nucleotides and suppressed by actin and does not occur at 25 degrees C, except in the presence of nucleotide. Here we show a similar temperature sensitivity and protection by actin of an analogous chymotryptic cleavage site in the heavy chain of gizzard S1. The results support the view that the myosin head, in general, can exist in two different conformational states even in the absence of nucleotides and actin, and indicate that the heavy chain region 5 kDa from the NH2-terminus is involved in the communication between the sites of nucleotide and actin binding. We also show here for the first time that the S1-S2 junction in gizzard myosin can be cleaved by chymotrypsin and that this cleavage (observed in papain produced S1 devoid of the regulatory light chain) is also temperature-dependent but insensitive to nucleotides and actin. It is suggested that the temperature dependent alteration in the flexibility of the head-rod junction, which is apparent from these and similar observations on skeletal muscle myosin [Miller, L. & Reisler, E. (1985) J. Mol. Biol. 182, 271-279; Redowicz, M.J. & Strzelecka Golaszewska, H. (1988) Eur. J. Biochem. 177, 615-624], may contribute to the temperature dependence of some steps in the cross-bridge cycle. PMID- 2209614 TI - Thymosins: both nuclear and cytoplasmic proteins. AB - A simple procedure based on perchloric acid extraction has been developed for the preparation and purification of bovine prothymosin alpha and thymosins beta 4 and beta 9 in high yields. Spectroscopic observations show these proteins to be non folding at neural pH. The cellular locations of human prothymosin alpha, rat parathymosin and calf thymosin beta 4, all so-called 'thymic hormones', have been studied by injection into the cytoplasm of Xenopus oocytes, followed by separate monitoring of nuclear and cytoplasmic concentrations. It is shown that human prothymosin alpha and rat parathymosin both migrate to the nucleus whilst thymosin beta 4 remains in the cytoplasm. The peptide (1-88) of calf prothymosin alpha is shown not to accumulate in the Xenopus nucleus, demonstrating that the C terminal 21 residues, which include a KKQK sequence, are required for nuclear migration. The present data, in association with existing evidence of wide tissue distribution and the lack of signal peptides, indicate that these proteins do not behave as hormones in the usual sense of the word. It is suggested that thymosin beta 4 should be grouped separately from the pro- and parathymosins. PMID- 2209615 TI - Effect of nucleotides, actin and temperature on thermolysin digestion of myosin subfragment-1. AB - Myosin subfragment-1 from rabbit skeletal muscle was digested by thermolysin at 25 degrees, 12 degrees and 0 degree C. Thermolysin cleaves subfragment-1 heavy chain into two stable fragments, 28 kDa and 70 kDa, aligned in this order from the N-terminus [Applegate, D. & Reisler, E. (1983) Proc. Natl Acad. Sci. USA 80, 7109-7112]. The rate of digestion at 25 degrees C was significantly increased in the presence of MgATP and somewhat less in the presence of MgADP, or magnesium pyrophosphate. This activating effect of the nucleotides was decreased at 12 degrees C and completely eliminated at 0 degrees C. The results can be explained by assuming that there are two subfragment-1 conformers [Shriver, J. W. & Sykes, B. D. (1981) Biochemistry 20, 2004-2012], and that both the addition of ATP or its analogs, and lowering the temperature, shift the conformational equilibrium in the direction that is more susceptible to thermolysin. Actin inhibited thermolysin digestion of subfragment-1 at all three temperatures studied. Actin inhibition can be explained either by shifting the equilibrium of the conformers in the direction of the less susceptible form or by direct interference of actin with the binding of thermolysin to subfragment-1. Actin inhibition of thermolysin digestion also prevailed when subfragment-1 was in a ternary complex with nucleotide and actin, in both the strongly and weakly attached states. Similarly, actin inhibited the digestion of subfragment-1 modified by 4-phenylenedimaleimide [corrected], which also forms a weakly attached complex with actin. No difference could be found in the accessibility of the thermolysin-susceptible site of subfragment-1 at the 28-70 kDa junction in either rigor, strongly or weakly attached states, which indicates the similarity of the structure proximal to this specific site in the three attached states. PMID- 2209616 TI - Expression of argininosuccinate lyase mRNA in foetal hepatocytes. Regulation by glucocorticoids and insulin. AB - Argininosuccinate lyase (ASL), the fourth enzyme of the urea cycle, belongs to a group of liver enzymes appearing in the late foetal period in the rat. Several hormones, including glucocorticosteroids and insulin have been implicated in the control of the development of this enzyme activity. In this study, the cloned cDNA was used to measure the relative abundance of ASL mRNA in the livers of rats at various stages of perinatal development and in cultured foetal hepatocytes during hormonal manipulations. The ASL mRNA was first detectable on day 15.5 of gestation and increased in amount concomitantly with the rise in the enzyme activity, suggesting that the appearance of enzyme activity reflects the turning on of specific gene transcription. When foetal hepatocytes were exposed to dexamethasone, an increase in ASL mRNA was detected, which was completely abolished by addition of actinomycin D, suggesting a transcriptional effect of the steroid. In contrast, administration of cortisol to foetuses in utero had no effect on the mRNA level, suggesting that the steroid action is inhibited in the intra-uterine environment. Insulin might be the inhibiting factor since it completely repressed the dexamethasone-induced accumulation of ASL mRNA in foetal hepatocytes. These data were confirmed in vivo by experiments using streptozotocin, which produces insulin-depleted foetuses and causes the accumulation of ASL mRNA. This regulation of ASL mRNA by glucocorticoids and insulin could account for the modulation of the enzyme activity observed in vivo and in vitro. PMID- 2209619 TI - NADP-dependent malate dehydrogenase (decarboxylating) from sugar cane leaves. Kinetic properties of different oligomeric structures. AB - NADP-dependent malate dehydrogenase (decarboxylating) from sugar cane leaves was inhibited by increasing the ionic strength in the assay medium. The inhibitory effect was higher at pH 7.0 than 8.0, with median inhibitory concentrations (IC50) of 89 mM and 160 mM respectively, for inhibition by NaCl. Gel-filtration experiments indicated that the enzyme dissociated into dimers and monomers when exposed to high ionic strength (0.3 M NaCl). By using the enzyme-dilution approach in the absence and presence of 0.3 M NaCl, the kinetic properties of each oligomeric species of the protein was determined at pH 7.0 and 8.0. Tetrameric, dimeric and monomeric structures were shown to be active but with different V and Km values. The catalytic efficiency of the oligomers was tetramer greater than dimer greater than monomer, and each quaternary structure exhibited higher activity at pH 8.0 than 7.0. Dissociation constants for the equilibria between the different oligomeric forms of the enzyme were determined. It was established that Kd values were affected by pH and Mg2+ levels in the medium. Results suggest that the distinct catalytic properties of the different oligomeric forms of NADP-dependent malate dehydrogenase and changes in their equilibrium could be the molecular basis for an efficient physiological regulation of the decarboxylation step of C4 metabolism. PMID- 2209620 TI - Site-specific N-glycosylation of ovine lutropin. Structural analysis by one- and two-dimensional 1H-NMR spectroscopy. AB - The Asn-linked carbohydrate structures of the heterodimeric glycoprotein hormone lutropin from ovine pituitary glands have been investigated at each of its three glycosylation sites using one- and two-dimensional 400-MHz 1H-NMR spectroscopy. Highly purified, biologically active ovine lutropin (oLH) was dissociated and separated into its alpha and beta subunits (oLH alpha, glycosylated at Asn56 and Asn82; oLH beta glycosylated at Asn13). Oligosaccharides from intact oLH beta and from glycopeptides obtained after tryptic digestion of oLH alpha were released by hydrazinolysis and subsequently fractionated according to charge and size by anion-exchange and ion-suppression amine-adsorption HPLC, respectively. 1H-NMR analysis revealed, that monosulphated, mostly hybrid-type, oligosaccharides predominate at both glycosylation sites of oLH alpha, whereas a disulphated, diantennary N-acetyllactosamine-type structure accounts for more than 60% of total oligosaccharides in the beta subunit. Furthermore, the saccharides attached to the beta subunit are almost completely fucosylated (Fuc alpha 1-6) at the reducing terminal GlcNAc, whereas the sugar chains in oLH alpha are either approximately 50% fucosylated (Asn82) or contain fucose only to a minor extent (Asn56). The results clearly indicate a distinct subunit- and site-specific synthesis of oligosaccharides in ovine lutropin and suggest that biosynthesis is effectively influenced by the surrounding polypeptide chain(s) at a given site. PMID- 2209618 TI - The complete amino-acid sequences of human ganglioside GM2 activator protein and cerebroside sulfate activator protein. AB - The complete amino-acid sequences of human ganglioside GM2 activator protein and cerebroside sulfate activator protein have been established by Edman degradation. The GM2 activator is composed of 162 amino acids, the first two serine residues being present in only 20% of the material. A single carbohydrate chain is N glycosidically linked to Asn32. Three hydrophobic alpha-helices may contribute to its lipid-binding site. Three amino acids differ from those found by cDNA sequencing which may be due to a polymorphism. The cerebroside sulfate activator consists of 80 amino acids and carries one N-linked carbohydrate chain at Asn21. The C-terminal valine residue is lacking in about 80% of the material. In spite their similar functions, both activator proteins show no sequence or structural similarities. PMID- 2209621 TI - A novel mycolic acid in a Mycobacterium sp. from the environment. AB - A fast-growing, non-photochromogenic mycobacterium isolated from the environment exhibited, on thin-layer chromatograms, a characteristic pattern of mycolates composed of unsaturated mycolates and also an unknown more polar component. Spectroscopic analysis and chemical degradation showed that this latter component was a novel mycolic acid containing a methoxy group at the omega-1 position (instead of omega-17 and omega-18 in known methoxymycolates), and two double bonds in the long mero aldehyde chain (instead of one as in known mycolates with additional oxygenated groups). PMID- 2209617 TI - The complete primary structure of two distinct forms of human alpha 1 (IX) collagen chains. AB - Type IX collagen molecules contain three genetically distinct subunits. One of the subunits, alpha 2(IX), contains a covalently attached glycosaminoglycan side chain. A second subunit, alpha 1 (IX), has been found to be synthesized in two forms. The two forms are generated by the alternative use of two transcription start sites and splice patterns. The two forms have been found in chicken, mouse and human but cDNAs encoding both forms have only been reported for chicken. In the present report we describe the isolation of cDNA clones encoding the complete translated portion of both forms of human alpha 1(IX) collagen chains. Nucleotide sequence analysis has permitted the determination of the primary structure of both forms. These probes and sequences should prove useful in future studies of chondrodysplasias involving type IX collagen. PMID- 2209622 TI - Construction and characterization of a recombinant murine monoclonal antibody directed against human fibrin fragment-D dimer. AB - cDNA libraries in lambda phage were generated from the murine hybridoma secreting mAb-15C5, a monoclonal antibody directed against fragment-D dimer of crosslinked human fibrin [Holvoet et al. (1989) Thromb. Haemostasis 61, 307-313], and clones encoding fragments of the heavy (gamma 1) and the light (kappa) chain were isolated. The kappa-chain cDNA was reconstructed from two overlapping clones encoding 20 amino acids of signal sequence and the 214 amino acids of the mature protein chain. The gamma 1-chain cDNA was reconstructed from the mAb-15C5 kappa chain signal sequence, the mAb-15C5 gamma 1 variable-domain coding sequence and murine gamma 1-gene and gamma 1-chain cDNA fragments encoding the constant domains. These cDNAs were expressed in Chinese hamster ovary cells, selected cell lines were scaled up in roller bottle culture, and recombinant mAb-15C5 was purified from the conditioned medium by chromatography on Zn-chelate - Sepharose, protein-A - Sepharose and insolubilized fragment-D dimer, with a yield of 50 micrograms/l and a recovery of 20%. SDS-gel electrophoresis without reduction revealed a homogeneous band, and after reduction a light-chain band with identical and a heavy-chained band with a somewhat slower mobility than that of the natural mAb-15C5. Competitive binding revealed a comparable affinity of natural and recombinant mAb-15C5 for fibrin fragment-D dimer. Thus recombinant mAb-15C5, obtained by co-expression of the reconstructed cDNAs of the kappa and gamma 1 chain in Chinese hamster ovary cells, has very similar properties to natural mAb-15C5. These recombinant mAb-15C5 cDNAs may be useful for the construction of a humanized monoclonal antibody for thrombus imaging, and for targeting of thrombolytic agents to fibrin. PMID- 2209623 TI - Primary structure of profilins from two species of Echinoidea and Physarum polycephalum. AB - Profilin is a small G-actin-binding protein, the amino acid sequence of which was previously reported for calf, human, Acanthamoeba and yeast. Here the amino acid sequences of three profilins obtained from eggs of two species of Echinoidea, Clypeaster japonicus (order, Clypeasteroida) and Anthocidaris crassispina (order, Echinoida), and plasmodium of Physarum polycephalum were determined. Two echinoid profilins were composed of 139 amino acid residues, N-termini were acylated and the molecular mass was calculated to be 14.6 kDa, slightly larger than that of 13 kDa estimated by SDS/PAGE [Mabuchi, I. & Hosoya, H. (1982) Biomed. Res. 3, 465 476]. On the other hand, Physarum profilin was composed of 124 amino acid residues, the N-terminus was acylated, and the calculated molecular mass was 13132 Da. The sequences of C. japonicus and A. crassispina profilins were homologous (84% identical). However, the similarity of these profilins with those form other organisms was low. The sequence of Physarum profilin was homologous with Acanthamoeba profilin isoforms (51% identical) and with yeast profilin (42% identical), but not with other profilins. The relatively conservative sequence of profilins from yeast, Physarum, Acanthamoeba, echinoid eggs and mammalian cells was found in the N-terminal region, which was suggested to be a common actin binding region. The C-terminal region was also conserved, although to a lesser extent than the N-terminal region. PMID- 2209624 TI - Characterization of the transcription-initiation site and of the promoter region within the 5' flanking region of the human aldolase C gene. AB - Several aldolase C clones from a human genomic library have been identified using a mouse aldolase C cDNA as a hybridization probe. The most complete fragment of the clones identified is 14 kb long and contains the complete aldolase C gene. The nucleotide sequence analysis of more than 5 kb includes the intron/exon organization structure of the gene and the 3' and 5' flanking regions. Although no human cDNA is yet available, a canonical polyadenylation signal at the 3' end of the gene indicates the proximity of the poly(A) addition site. We have analyzed the 5' noncoding region by S1 mapping and primer-extension experiments. The transcription-initiation sites for the human aldolase C gene in brain tissue was located about 1300 bp upstream from the methionine initiation codon. Preliminary functional assays of the promoter by transfection into rat glioma cells have indicated that promoter elements lie between positions -161 and -416 from the start point of transcription. PMID- 2209626 TI - Typing of coagulase-negative staphylococci by Southern hybridization of chromosomal DNA fingerprints using a ribosomal RNA probe. AB - Ribotyping consists of restriction endonuclease fingerprinting of ribosomal RNA (rRNA) genes visualized by Southern hybridization with an rRNA probe. This method was developed and compared with restriction endonuclease fingerprinting of chromosomal DNA for typing coagulase-negative staphylococci. Twenty-five American Type Culture Collection reference type strains and 53 clinical isolates were typed. Both methods clearly distinguished all 15 species of coagulase-negative staphylococci and most individual strains within each species. Except in the case of Staphylococcus warneri, ribotyping was most discriminating with the use of ClaI, one of eight endonucleases tested. HpaI and AvaI were more specific than ClaI for discrimination between strains of Staphylococcus warneri. The patterns produced by ribotyping were much simpler and thus easier to interpret than corresponding chromosomal fingerprints. However, ribotyping was slightly less discriminating. It is concluded that ribotyping offers an alternative method for molecular typing of coagulase-negative staphylococci. The application of both methods needs to be further evaluated in the clinical setting. PMID- 2209628 TI - A probe for the detection of methicillin-resistant Staphylococcus aureus. AB - An approximately 300 base pair DNA fragment for use as a probe was isolated from methicillin-resistant Staphylococcus aureus DNA partially digested with Sau3AI. This probe hybridized with 25 methicillin-resistant clinical isolates of Staphylococcus aureus belonging to 18 different phage types, but not with 41 clinical isolates susceptible to methicillin. PMID- 2209627 TI - Rapid microscopy technique for detection of Pneumocystis carinii in fresh clinical specimens. AB - A direct method for detection of Pneumocystis carinii was evaluated in 14 patients with impaired immune function (3 seropositive for HIV, 8 with AIDS and 3 with heart transplants) and signs and symptoms suggestive of Pneumocystis carinii pneumonia. Direct examination by phase-contrast and interference-contrast microscopy of fresh clinical specimens obtained by sputum induction, bronchoalveolar lavage or transbronchial lung biopsy was found to be a simple and rapid method for detection of Pneumocystis carinii, the sensitivity of the method being comparable to that of the classical toluidine blue O and Diff-Quik staining methods. These findings suggest that this direct microscopy technique could be considered for routine clinical application in patients with suspected Pneumocystis carinii pneumonia. PMID- 2209629 TI - Rapid presumptive phenospecies identification of mesophilic aeromonads by testing for suicidal activity. AB - A new test combination for presumptive phenospecies identification of mesophilic aeromonads by testing for suicidal activity in conjunction with esculin hydrolysis and gas production from glucose was evaluated. Of 40 clinical isolates of Aeromonas tested statically at 30 degrees C, seven were identified as Aeromonas hydrophilia (non-suicidal, aerogenic, esculin positive), eight as Aeromonas sobria (suicide variable, mostly aerogenic, esculin negative), and 25 as Aeromonas caviae (suicidal, anaerogenic, esculin positive). The results corresponded exactly to those obtained with the conventional biochemical tests. The test combination was rapid and simple to perform. PMID- 2209625 TI - Immunological aspects of fungal pathogenesis. AB - The incidence of infection with the pathogenic fungi continues to escalate, especially in the era of the acquired immune deficiency syndrome. To the clinician, this heterogeneous group of organisms poses both a diagnostic and a therapeutic challenge. Consequently, growing numbers of investigators are seeking to elucidate the pathogenetic mechanisms involved in disease caused by medically important fungi. In this review, many of the recent scientific advances that have been made in the immunological aspects of the pathogenesis of fungal infections are presented. The topics covered include 1) the receptors for fungi on the surface of professional phagocytes; 2) the mechanisms for killing and growth inhibition of fungi by phagocytes; 3) the means by which fungi evade host defenses; 4) the role of humoral immunity in fungal infection; 5) immunoregulation in fungal infections; and 6) the influence of cytokines on host defenses against pathogenic fungi. PMID- 2209630 TI - In vitro antibacterial activity and beta-lactamase stability of the new carbapenem LJC10,627. AB - In in vitro susceptibility tests the new carbapenem LJC10,627 showed potent antibacterial activity against gram-positive and gram-negative bacteria, except that most methicillin-resistant Staphylococcus aureus strains tested were found to be resistant to LJC10,627. LJC10,627 showed high activity against Pseudomonas aeruginosa and was active against Enterobacter cloacae and Citrobacter freundii strains which were resistant to ceftazidime and cefpirome. The Ki values of LJC10,627 for penicillinase Type I, cephalosporinase and oxyiminocephalosporinase were low, whereas the Ki value for L-1 enzyme from Xanthomonas maltophilia was high. PMID- 2209631 TI - Pseudomonas paucimobilis peritonitis in a patient on CAPD successfully treated with ciprofloxacin and netilmicin. PMID- 2209633 TI - Testing for high-level aminoglycoside resistance in enterococcal infections. PMID- 2209632 TI - Oral and intestinal microflora in individuals with different immunoglobulin deficiencies. PMID- 2209634 TI - Clinical experience in gynecological cancer management. b) Vulvar cancer: report from the Gynecologic Institutes of Padua University (1963-1989). AB - A review of the case series of our Institute from 1963 to 1989 (197 patients) permits some considerations and conclusions on the clinical management of vulvar cancer. In the aim of prophylaxis, prevention and early detection, personalized screening must be systematically performed in clinical practice by the Gynecologist. Surgical Pathological Staging (post-surgical FIGO stages) is mandatory for the exact knowledge of local tumor spread, lymph nodal involvement, aggressiveness factors and possible neoplastic multicentricity. In our experience operability is now 93%, with pathological radicality in 93% of operated cases. In early stages lymph nodal involvement is low (8.6% in tumor less than 2 cm; post surgical FIGO stage I) but it is very high in advanced cases. Surgery is the treatment of choice both in early and advanced stages. The increasing incidence of early vulvar cancer in young women has obliged us to reduce the cost to the patient of the surgical strategy to avoid mutilation in order to improve the quality of life without endangering survival. With this aim, since 1975 we have been performing an enlarged non mutilant radical vulvectomy which allows a better post operative period, with a low rate of complications and the preservation of anatomo-functional integrity. Furthermore 5 year survival rate appears unchanged while the quality of life greatly improves in cases treated by non mutilant operation. In any case of invasive tumor bilateral systemic inguinal lymphadenectomy must be performed and frozen biopsies are useful for planning the best surgical strategy. Integrated therapies are useful in advanced cases and in lymph nodal involvement. Close follow-up is mandatory. PMID- 2209635 TI - The potential of primary cytoreductive surgery in patients with FIGO stages III and IV ovarian carcinoma. AB - The present study included 40 patients with advanced ovarian carcinoma who underwent surgery and combination chemotherapy with cisplatin or carboplatin at the Department of Gynecology and Obstetrics of the University of Pisa. All the 20 optimally cytoreduced (residual disease lower than 2 cm) patients were clinically free of disease after the sixth course of chemotherapy; second-look laparotomy showed a pathological complete response (PCR) in 16 of them (80%). The 5-year actuarial progression- free and overall survival rates of this group of patients were 44.0% and 82.2% respectively. Among the 20 patients with residual disease greater than 2 cm after the first laparotomy, a clinical complete response was obtained in 3 (15%) and a clinical partial response in 12 (60%); a PCR was achieved in only 1 (5%) of them. The 5-year actuarial progression- free and overall survival rates of this group of patients were 0% and 14.2% respectively. The present paper confirms that surgery plays a major role in the treatment of ovarian carcinoma. Aggressive surgical removal with optimal tumor reduction can produce a favourable effect on patients survival time, since there is an inverse relationship between the volume of residual disease after the first laparotomy and the likelihood of response to chemotherapy. PMID- 2209636 TI - Treatment of advanced or recurrent adenocarcinoma of the endometrium with doxorubicin and cyclophosphamide. AB - Thirteen patients with recurrent or advanced endometrial carcinoma were treated with a combination of doxorubicin (40 mg/m2 IV) and cyclophosphamide (600 mg/m2 IV). All patients had been refractory to prior radiotherapy and hormone therapy. None of the patients had received prior chemotherapy. Six of the 13 patients (46%) achieved an objective response: 1 complete response (8%) and 5 partial responses (38%). Median overall survival was 10 months (range 3-20 months). Doxorubicin and cyclophosphamide is an active combination in patients with advanced endometrial cancer. PMID- 2209637 TI - T lymphocytes in non-malignant, pre-malignant and malignant changes of the cervix. AB - T lymphocytes play an important role in the immune response to both neoplasia and viral infection. Normally about 60% of T lymphocytes in the peripheral blood are T4 lymphocytes, while 20-30% are T8 ones. The T4/T8 ratio is usually 2:1. When this ratio is inverted the most significant changes occur. The aim of our study was to examine the T4/T8 lymphocyte ratio in the peripheral blood of patients with histologically confirmed non-malignant and premalignant changes of the cervix and to compare it both with the ratio in patients with squamocellular carcinoma of the cervix and those without any cytological or colposcopical cervical abnormality. The study group consisted of 118 patients, 17 of them had leukokeratosis of the cervical epithelium, 20 had cervical intraepithelial neoplasia (CIN) and 42 patients had cervical cancer, 39 patients had normal cervical findings and comprised the control group. Peripheral blood lymphocytes were examined by indirect immunoperoxidase technique, using OKT 4 and OKT 8 monoclonal antibodies. The average T4/T8 lymphocyte ratio in the peripheral blood of patients with leukokeratosis was 1.55, and in those with CIN 1.19. In patients with cancer the ratio was 1.34. The differences was not statistically significant. The control group had an average T4/T8 ratio of 2.31 which was significantly different compared to the results of the other groups. The value of these and similar results obtained by other authors is still uncertain. The alteration of T lymphocyte subsets may occur in the peripheral blood of patients with viral infections and some viruses are considered important in the etiology of CIN.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2209638 TI - Immunoscintigraphy in the follow up of patients with ovarian cancer. AB - Our case series concerns eight patients affected by epithelial cancer of the ovary. The immune scintigraphical examination with B 72.3-I-131 monoclonal antibody was carried out as a follow-up after surgical therapy with chemo- and/or radio-therapy. The results were compared with traditional diagnostic methods (CT, pelvic echography etc.). The immunoscintigraphy confirmed the presence of local relapses in seven patients, correlating positively with the results of conventional enquiries. The conclusions, although relating to a limited number of cases, are satisfactory and seem to indicate important diagnostic possibilities to the end of follow-up in patients affected by ovarian cancer. PMID- 2209640 TI - CA 125 in monitoring chemotherapy of the patients with ovarian cancer. AB - Changes in CA 125 antigen concentration and serum half-life were determined in 63 women with ovarian carcinoma during chemotherapy following various types of surgery. Concentration of CA 125 in serum correlated with the degree of clinical advancement of the tumor, 20.00 and 688.84 U per ml at stages I, II, and IV, respectively, and with remaining tumor mass, despite chemotherapy, serum CA 125 level rose after exploratory surgery. Estimation of CA 125 levels proved less useful in the mucinous type of ovarian carcinoma. The treatment scheme including Cisplatinum reduced CA 125 levels most effectively correlated with good clinical response to the therapy. Testing the half-life time appeared to provide a good prognostic index, 6.25 +/- 2.08 days after radical surgery and 44.87 +/- 26.5 days after probatory laparotomy. PMID- 2209639 TI - Malignant lymphoma of the ovary: report on two cases and review of the literature. AB - Two cases of malignant lymphoma of the ovary observed at the Division of Medical Oncology of the II Medical School of Naples, are described. One patient had a diffuse immunoblastic lymphoma confined to the ovaries, after accurate clinical pathological staging. She received aggressive chemotherapy after surgery, and is disease free over one year after diagnosis. The second patient had a low grade lymphoma of the ovary that had spread throughout the abdomen. This patient failed to respond to first line chemotherapy. The literature on ovarian involvement by lymphoma is also reviewed, and prognosis according to different stages of the disease is explained. PMID- 2209641 TI - Evaluation of some hemostatic parameters in patients with cervical carcinoma. AB - It is well known that cancer induces changes in hemostasis. Plasma levels of Fibrinopeptide A (FPA), D-Dimer (DD), von Willebrand Factor (FvW) and fibrinogen were-assayed at diagnosis in 66 patients with cervical carcinoma and in 67 healthy women as controls. FPA, DD and fibrinogen levels were significantly higher in patients with FIGO stage I b-IIa cervical carcinoma than in controls (2.25 +/- 0.25 vs 1.19 +/- 0.15 p less than 0.001; 307 +/- 35 vs 112 +/- 8 p less than 0.001; 375 +/- 23 vs 280 +/- 17 p less than 0.001 respectively). A further increase of DD, FPA but not of fibrinogen concentrations was observed in advanced stages of disease (3.52 +/- 0.81 vs 2.25 +/- 0.25 p less than 0.1; 943 +/- 98 vs 307 +/- 35 p less than 0.001; 407 +/- 26 vs 375 +/- 23 p = NS respectively). FvW levels in patients with early stage cervical carcinoma were in the normal range, while in patients with advanced cancer, they were significantly higher (175 +/- 8 vs 104 +/- 2 p less than 0.001). A significant correlation was found between plasmatic levels of FPA and DD, FPA and FvW, DD and FvW (r = 0.57 p less than 0.01; r = 0.76 p less than 0.01; r = 0.54 p less than 0.01 respectively). Our data seem to indicate that in patients with cervical carcinoma, and in particular in those with advanced cancer, there is an activation of blood coagulation and fibrinolysis. PMID- 2209643 TI - Treatment of patients with sarcoma of the uterus. AB - In the present series of 156 patients with sarcomas of the uterus the therapeutic modalities employed were evaluated. The 5-year survival rate of 51.3% was obtained for this series including 41.2% for leiomyosarcomas, 57.1% for endometrial stromal sarcomas, 50.0% for mixed mesodermal tumors and 40.0% for carcinosarcomas. The prognostic significance of the extent of disease, histological type and the age of patients is emphasised. Clinical features of uterine sarcomas specific for different histological types were shown: leiomyosarcomas were characterized by a rapid tumor growth while uterine bleeding in the background of neuroendocrine disturbances similar to those observed in endometrial carcinomas were related to endometrial stromal sarcomas and mixed mesodermal tumors. In respect to early diagnosis of sarcomas an ultrasonic pelvic examination and studies of aspirate specimens taken from the uterine cavity are recommended to be performed for the groups at high risk. An individual treatment policy was developed for each sarcoma patient depending on the histological type, the stage of disease and general condition of the patient. Surgical approach varied ranging from a total hysterectomy and adnexectomy, done for leiomyosarcomas, to an extended hysterectomy and pelvic lymphadenectomy for mixed mesodermal tumors and endometrial stromal sarcomas. Postoperative distant and/or endovaginal radiation are indicated for all histological types of sarcomas excepting leiomyosarcomas. Application of adjuvant chemotherapy with carminomycin or adriamycin improves the results of treatment. PMID- 2209642 TI - Phase II study of carboplatin and cyclophosphamide combination chemotherapy for the treatment of advanced ovarian cancer. AB - The efficacy and toxicity of intravenous carboplatin (300 mg/m2) and cycloprosphamide (600 mgs/m2) was evaluated in 44 newly diagnosed patients with advanced stage epithelial ovarian cancer. Cycles were administered at four weekly intervals for a total of 6 cycles, and therapy was provided on an out-patient basis without prehydration or forced diuresis. During treatment patients were assessed by physical, gynaecological and radiological examinations. Forty-four patients with a median age of 54 years (range 28-76) were entered into the study. The majority of patients had serous cystadenocarcinoma, 82% had stage III or IV disease and 87% had grade II or III histologic subtype. Optimal debulking surgery was carried out in only 46% of patients. The overall response rate to carboplatin/cyclophosphamide was 73%, with 55% achieving a clinical complete response. The median survival for all patients was 18+ months (range 2-41+). For those patients who received optimum surgery, median survival was 26+ months, compared with 11+ months for those whose lesion could not be completely resected. Treatment was well tolerated by most patients, with significant nausea and vomiting (WHO grade III-IV) observed in only 11% of 226 cycles of therapy. Myelosuppression was acceptale, with a mean nadir white cell count 4.3 x 10(9)/L (range 1.4-9.0) and a mean nadir platelet count of 273 X 10(9)/L (range 39-536) observed on day 21. There were no therapy-related infective episodes. Significant alopecia developed in 4 patients, but significant nephrotoxicity, ototoxicity or neurotoxicity has not been observed in any patients. This study demonstrates that combination carboplatin/cyclophosphamide is well tolerated in women with advanced stage epithelial ovarian cancer and produces overall response rates and median survival similar to those obtained with cisplatin-containing chemotherapy. PMID- 2209645 TI - Radiation protection and the staff of nuclear medicine departments. PMID- 2209644 TI - Prognostic factors in endometrial cancer. AB - The 5 year survival rates of 228 patients with endometrial cancer treated in the period 1978-1982 according to the prognostic factors (stage, grade, depth of myometrial invasion, lymph node metastasis) is presented. All patients were treated with primary surgery consisting of classical Wertheim operation with lymphadenectomy (98 cases-43%), total abdominal hysterectomy with bilateral salpingo-oophorectomy with lymphadenectomy (52 cases-48%) and without lymphadenectomy (55 cases-52%) and vaginal hysterectomy with bilateral salpingo oophorectomy (23 cases-10%). All patients except 6.6% were postoperatively irradiated. The 5 year survival for all stages was 74.6%. In SI cases it was 83.8%, in SII 57.9% and only 37.5% in SIII group. The survival was 90.1% in patients with superficial myometrial invasion and 56.4% in cases of deeper invasion. The survival of patients with node metastasis (8.6%) was only 39.5%, irrespective of the type of surgery and postoperative external irradiation. Vaginal recurrences were observed in 3.9%, and all the patients died. To improve the results it is necessary to individualize the treatment according to the pathologic and clinical prognostic factors. PMID- 2209646 TI - Rapid background reduction of circulating sodium iodide I 125-labelled Pisum sativum agglutinin used as a tumor-imaging radiopharmaceutical by the chemically galactosylated antibody. AB - Influence on the clearance of background radioactivity from the blood was studied by using a chemically galactosylated antibody to the radiopharmaceutical. Sodium iodide I 125-labelled Pisum sativum agglutinin (125I-PSA) was used as the model tumor-imaging radiopharmaceutical in this series of experiments. Rabbit (anti PSA) immunoglobulin G (IgG) was chemically galactosylated with varying amounts of cyanomethylgalactose. Galactose concentration ranged from 11 to 17 mol/mol protein. Antibody activity was not affected by chemical galactosylation under the experimental conditions used. Blood clearance of the galactosylated anti-PSA (GAP) in normal mice was enhanced to varying degrees, depending on the degree of galactosylation; similarly, liver uptake was increased with the degree of galactosylation. Following injection of 125I-PSA in normal mice, the lectin was rapidly removed from the blood by subsequent injection of GAP. Increased hepatic uptake of the complex (lectin-galactosylated antibody) via protein-carbohydrate recognition caused the pronounced decrease in the 125I-PSA blood level. The effective time for 125I-PSA removal was as short as 15 min. The potency was dependent on the degree of galactosylation of the antibody. In sarcoma 180 (S 180) tumor-bearing mice, the capacity for blood clearance of 125I-PSA was also positively correlated to the degree of galactosylation. Moreover, the variation in the delivered dose ratio of antibody to lectin proved to lead to a further increase in background clearance. As a result, especially the tumor:blood ratio was significantly improved by a single administration of chemically galactosylated antibody, as compared with the value measured in the presence of unmodified antibody. These initial studies suggest that administration of GAP may improve nuclear imaging with radiopharmaceuticals. PMID- 2209648 TI - Blood pool ventriculography with a new technetium-labelled complex (99mTc-DEPIC): a clinical evaluation. AB - A new, single bolus method of in vivo blood pool imaging using a technetium Tc99m phosphine isocyanide complex (DEPIC) which binds to pre-albumin was evaluated in volunteers (n = 4) and patients (n = 20). DEPIC was assessed for its safety and possible drug interactions. Its duration of action and quality of ventriculography were compared with imaging using standard in vivo red cell labelling (PYP) during two 3-h scanning periods 1 week apart. DEPIC had a mean plasma half-life of 3.3 h. The count rate over the left ventricle was initially 42% higher with DEPIC than with PYP. However, removal of DEPIC by the liver resulted in equivalent count rates by 1 h, and by 3 h PYP count rates were 22% higher than DEPIC. Immediately post injection mean (SD) difference in the left ventricular ejection fraction between the two methods was 2.4% (7.7%). Satisfactory DEPIC scans were obtained up to 2 h post injection, but by 3 h there was a mean difference of 13% (11.3%). DEPIC was found to be a safe alternative to red all labelling for blood pool angiography, suitable for routine work. The single bolus methodology and high initial count rates offer improved efficiency and a capability for truly emergency scanning. PMID- 2209647 TI - Detection of experimental thrombi in rabbits with an 131I-labelled fibrin specific monoclonal antibody. AB - The detection of thrombi in rabbits has been investigated with 131I-labelled DD 3B6/22, a monoclonal antibody (Mab) reactive at high affinity (Kd = 2.68 x 10( 10) M) with human D Dimer (DD). DD-3B6/22 bound well to both "fresh" and "aged" human clots in an in vitro assay but showed poor binding to rabbit clots. However, reactivity was restored to rabbit blood if it was seeded, before clotting, with human DD covalently coupled to Sepharose beads. Thus, a rabbit model was developed in which blood was allowed to clot around DD-Sepharose beads introduced into the jugular vein. Gamma camera imaging showed that intact 131I labelled DD-3B6/22 localised to these clots within 24 h. Uptake at this time was 0.202 +/- 0.012% injected dose per gram (%ID/g) compared with 0.086 +/- 0.018%ID/g after injection of control antibody. 131I-labelled F(ab')2 fragments of DD-3B6/22 allowed earlier scintigraphic detection of the clot which was evident 4 h after injection. Uptake in the clot at 24 h was 0.154 +/- 0.038 %ID/g compared with 0.109 +/- 0.027 %ID/g for a control F(ab')2. As antigen levels in the clot are estimated to be less than 300 micrograms DD, thus representing a very small human clot, the DD-3B6/22 Mab would appear to have a good potential for the sensitive detection of thrombi in a clinical setting. PMID- 2209649 TI - Quantitation of left ventricular asynchrony on radionuclide angiography phase images. AB - Quantitation of left ventricular (LV) asynchrony is relevant in clinical cardiology, as well as in evaluating LV mechanical properties. Radionuclide angiography (RA) phase images are extensively used, and asynchrony is usually assessed by computing the standard deviation of phase angle distribution (SD). However, SD is dependent on count statistics and does not take into account the spatial distribution of asynchrony. In this study a new index to evaluate asynchrony on phase images is presented (differential uniformity parameter, DUP). DUP is based on the frequency analysis of phase images. Diagnostic accuracy and reproducibility of either SD or DUP were tested. Reproducibility was evaluated in 15 patients studied by RA twice within a few minutes. DUP showed a better reproducibility than SD. Diagnostic accuracy was estimated in 84 patients, divided into four subgroups on the basis of coronary arteriography and contrast ventriculography findings: (a) 25 control subjects, (b) 16 patients with coronary artery disease (CAD) and normal LV wall motion, (c) 23 patients with CAD and LV hypokinesia and (d) 20 patients with CAD and LV dyskinesia. Relative diagnostic ability was assessed by comparing the areas under receiver-operating characteristic curves. DUP's area was larger than SD's when group D was tested against all the other groups (DUP's area = 87% +/- 5%, SD's area = 76% +/- 7%; P less than 0.01). Thus, our study indicates that DUP is more reproducible and more accurate than SD in identifying patients with CAD and LV dyskinesia. PMID- 2209650 TI - In vivo characterisation of 3-iodo-6-methoxybenzamide 123I in humans. AB - 3-Iodo-6-methoxybenzamide (123I-IBZM), a new Dopamine D2 receptor ligand, was used in conjunction with SME 810 brain tomography to study six subjects (one normal volunteer, four schizophrenics and one DAT patient). Initial Dynamic SPET was followed by multislice SPET. High-resolution images of the D2 receptor distribution in the basal ganglia were obtained. The specific binding in D2 receptors of the basal ganglia is highest from 2-4 h p.i. Patients on anti psychotic drugs showed significantly lower specific binding. Dopamine D2 brain receptor availability in man may now be studied with SPET. Continuous data acquisition with single slice tomography is particularly important in the study of this type of radiotracers. PMID- 2209651 TI - Abnormal 67Ga uptake in a fibrosarcoma of the pericardium with malignant transformation. AB - A 31-year-old woman presented with general malaise, back pain, and edema of the lower extremities. A chest X-ray film showed an enlarged cardiac shadow and clear lung fields. A pericardial lesion with decreased activity on blood pool imaging and increased uptake on gallium citrate imaging displaced the heart upwards and to the left. The pericardial mass showed an inhomogeneous signal intensity on MRI and was large enough to obstruct the venous return by compressing the heart. At operation, the mass was found to originate from the pericardium and was histologically identified as a malignant fibrosarcoma. Twelve years previously, the patient had undergone an operation for the removal of a pericardial tumor which was histologically identified as a benign hemangioma. In view of the rarity of pericardial tumors, the present tumor is suspected to have undergone a transformation from benign hemangioma to malignant fibrosarcoma. PMID- 2209652 TI - Lymph-node scintigraphy. PMID- 2209653 TI - Gilles de la Tourette's syndrome. PMID- 2209654 TI - Comparison of technetium 99m-phytate and technetium 99m-sulphur colloid in primary bone tumours. AB - Eleven patients with proven primary bone tumour (five Ewing sarcomas, six osteosarcomas) and two cases of metastatic bone involvement (primary other than bone) were investigated with 99mTc-phytate and 99mTc-sulphur colloid to compare the behaviour of the two radiopharmaceuticals at the tumour site. After intravenous administration of the respective radiopharmaceutical, imaging of the tumour site and its contralateral part was carried out at 15 min and 1 h intervals. The data were stored in our computer. Bone scanning was also carried out in all patients. 99mTc-phytate uptake was observed at the tumour site in ten cases. The 99mTc-sulphur colloid study revealed sparse or no significant uptake in eight cases. In two patients, with osteosarcoma 99mTc-sulphur colloid investigation showed uptake at the primary tumour site. However, the distribution pattern is different from that of 99mTc-phytate. No significant uptake of either 99mTc-phytate or 99mTc-sulphur colloid was observed in the two patients with metastatic skeletal disease. It may be concluded that the unusual accumulation of 99mTc-phytate at the tumour site is not due to any generalized reticuloendothelial phenomenon and that the radiopharmaceutical itself is responsible for this. PMID- 2209655 TI - Detection of arterial thrombosis after laser angioplasty by platelet scintigraphy. AB - Indium-111-labelled platelet scintigraphy was performed in two patients after laser-assisted balloon angioplasty. Both patients demonstrated a significant 'hot spot' at the angioplasty site 24 h after successful recanalisation with laser and balloon. Clinically apparent thrombosis of the recanalised arteries occurred 5 and 6 days after angioplasty in both patients. Laser-assisted balloon angioplasty leads to significant platelet deposition over recanalised segments of the artery, which may result in arterial thrombosis, as evident from the reports presented. Indium-111-labelled platelet scintigraphy emphasises the extent of trauma caused by laser and balloon angioplasty to the arterial wall. PMID- 2209657 TI - Highlights of the European Association of Nuclear Medicine Congress, Amsterdam 1990. PMID- 2209656 TI - European multi-centre comparison of thallium 201 and technetium 99m methoxyisobutylisonitrile in ischaemic heart disease. AB - Fifty-six patients in Europe were entered into a multi-centre study to compare the accuracy of technetium 99m methoxyisobutylisonitrile (99mTc-MIBI) for the detection of coronary artery disease (CAD) with thallium 201 (201Tl) chloride perfusion scanning. The results showed a high degree of concordance between the two radiopharmaceuticals. Some 81% (678/840) of myocardial segments showed the same result (normal, infarct or ischaemia), and 80% (45/56) of patients had the same diagnosis. Overall detection of CAD in patients was 98% for 201T1 and 96% for 99mTc-MIBI. Detection of CAD in total arteries was 68% for both agents. In this study 99mTc-MIBI was as accurate as 201Tl for the detection of coronary artery stenoses. PMID- 2209658 TI - Gastro-oesophageal reflux and apnoeic pauses during sleep in infancy--no direct relation. AB - We studied the relation of gastro-oesophageal reflux with apnoea during sleep in 24 infants with antecedent respiratory abnormalities and/or proven gastrooesophageal reflux (GOR), by combined lower oesophageal pH and polygraphic monitoring. GOR, indicated by pH less than 4, was confirmed in 24 infants. There were no episodes of prolonged (greater than 20 s) central apnoea (CA). Fifty-six mixed or obstructive breathing episodes were identified in 12 infants (14 studies), of which 28 lasted between 3 and 6 s. Bradycardia (heart rate less than less than 80 beats/min for 10 s was not observed. There were 80 falls in transcutaneous oxygen (PtcO2 greater than 5 mmHg) but only 6 exceeded 10 mmHg and one 20 mmHg. There was no relationship between GOR and obstructive episodes in terms of frequency, duration or temporal occurrence, except in one infant. There were 1276 gross body movements, mainly during active or indeterminate sleep and, of these, 7% were associated with decreases in pH to less than 4. Movements occurred during the 60 s period preceding 83% of pH decreases greater than 1 pH unit compared to only 30% in the 60 s succeeding a pH drop. We conclude that, while GOR and obstructive episodes may co-exist in the patient groups studied, decreases in pH in the lower oesophagus do not usually induce either central or obstructive apnoea, and vice versa. Of the variables monitored, only gross body movements were temporally associated with pH drops, and usually preceded them. PMID- 2209659 TI - Acceleration of linear growth following intestinal resection for Crohn disease. AB - Twelve patients with Crohn disease aged from 11.3 to 17.1 years, underwent intestinal resection. Eight were prepubertal or in early puberty and 4 in mid or late puberty. Pre-operative assessment included acceleration and compression barium studies and total colonoscopy. In six patients the surgical indication was failure of medical management and in six intestinal obstruction. All but one were in remission 12 months after surgery. Height velocities in the eight pre and early pubertal patients increased dramatically during 6- and 12-month post operative measurement periods compared with preoperative growth. Height velocities in the mid and late pubertal patients showed much less increase. In selected patients, surgical treatment can induce remission resulting in catch-up growth and sustained growth acceleration. In prepubertal and early pubertal patients surgery is likely to improve final adult height. PMID- 2209661 TI - Herniation of calcifying discopathy in childhood: report of three cases. AB - Herniation of the calcified nucleus pulposus through the fibrous annulus is unusual in childhood. We present three cases and have surveyed 32 cases in the literature. Most herniations are located in the lower cervical and upper thoracic spine. Herniation is usually symptomatic. Usually calcification decreases after some months. For most children conservative therapy with bedrest and analgesics is sufficient. PMID- 2209660 TI - Agranulocytosis following infectious mononucleosis. AB - A girl developed acute agranulocytosis (45/mm3), 37 days after the onset of infectious mononucleosis. The bone marrow showed myeloid hyperplasia with maturation arrest and erythroid hypoplasia. A normal amount of colony forming units of granulocytes and macrophages (CFU-GM) colonies with a relative high number of clusters was observed. Neither anti-neutrophil antibodies nor circulating inhibitors of colony growth were found in serum. Granulocyte and macrophage colony stimulating factor (GM-CSF) activity in the patient's serum rose at this time. The agranulocytosis lasted 5 days and her clinical state soon improved. These results suggested that agranulocytosis was presumably not due to serum factors, including auto-antibodies and/or suppressive substances, and that Epstein-Barr virus (EBV) had some direct or indirect effect on the marrow cells of the myeloid series. PMID- 2209662 TI - Echo planar imaging of an infant with pectus excavatum. AB - Echo planar imaging has enabled us to image safely and without sedation the thorax of an infant with pectus excavatum deformity. The heart was displaced into the left side of the thorax, and the right lung was calculated to be 1.6 times larger than the left lung. PMID- 2209663 TI - Bare lymphocyte syndrome--combined immunodeficiency and neutrophil dysfunction. AB - A 4-year-old girl presented with recurrent infections. Immunoglobulin deficiency (serum and secretory IgA, serum IgG3) neutropenia and neutrophil dysfunction (defective spontaneous migration and chemotaxis) were found. T-lymphocyte counts were normal and they responded to phytohaemagglutinin but were not stimulated by Concanavalin A, pokeweed mitogen and microbial antigens in vitro. Delayed cutaneous hypersensitivity testing to purified protein derivative and candidin was negative. Despite bacille Calmette-Guerm vaccination and candidiasis, near normal beta-2-micro-globulin and human leucocyte antigen (HLA) class I concentrations were detected on mononuclear cells and phytohaemagglutinin-induced lymphoblasts. HLA class II antigens (HLA-DP, -DQ, -DR) were not expressed. These observations indicated a bare lymphocyte syndrome (BLS) type II. This is the first time neutrophil dysfunction has been noted in association with BLS. PMID- 2209664 TI - Neuroblastoma in a patient with dihydropteridine reductase deficiency. AB - Tetrahydrobiopterin (BH4) deficiency is a rare cause of hyperphenylalaninaemia (HPA) and usually leads to progressive neurological deterioration despite early dietary control of plasma phenylalanine concentrations. Dihydropteridine reductase (DHPR) deficiency is the most severe cause with respect to a fatal outcome. We report a 7-year-old girl with HPA diagnosed on neonatal Guthrie screening who at the age of 6 months had cytotoxic therapy for an adrenal neuroblastoma which secreted catecholamines. When 4 years old she was found to have DHPR deficiency. Although developmentally retarded and microcephalic she has failed to develop the florid neurological features often associated with the condition. PMID- 2209665 TI - Low-density lipoprotein plasmaphaeresis with and without lovastatin in the treatment of the homozygous form of familial hypercholesterolaemia. AB - A 7-year-old girl with homozygous familial hypercholesterolaemia and plasma low density lipoprotein(LDL)-cholesterol levels of 820 mg/dl (21.2 mmol/l) and progressive xanthomata was treated with heparin extracorporeal low-density lipoprotein precipitation (HELP) to lower her plasma LDL. On weekly HELP treatment she maintained her pre-HELP treatment LDL-cholesterol levels at 409 mg/dl (10.6 mmol/l). The long-term HELP treatment was well tolerated and led to regression of her xanthomata. Subsequently, lovastatin [Mevacor; Merck Sharp & Dohme, Westpoint, Pa., USA (20 mg/day)] was added to the regimen, causing a further 20% decrease in her pre-HELP treatment plasma LDL-cholesterol levels. Lovastatin alone did not sufficiently lower her plasma LDL and could not replace the weekly HELP therapy. Our data show that lovastatin is an effective adjunctive therapy for lowering plasma LDL-cholesterol in a homozygous patient, once plasma LDL levels have already been lowered by regular HELP treatment. PMID- 2209666 TI - Peroxisomal beta-oxidation defect with detectable peroxisomes: a case with neonatal onset and progressive course. AB - A progressive demyelinating cerebral disorder is described in a normally appearing female infant with neonatal seizures, progressive psychomotor deterioration, deafness, retinopathy, peripheral neuropathy and loss of myelin observed on magnetic resonance imaging (MRI) scanning. MRI also showed the absence of macroscopic neocortical dysplasia which is usually found in Zellweger syndrome (ZS). Adrenal cortical function was normal. The patient died at the age of 37 months. Extensive biochemical investigations of peroxisomal functions in the patient revealed an impairment of peroxisomal beta-oxidation resulting in elevated levels of very long (greater than C22) chain fatty acids in plasma and fibroblasts. Moreover, elevated plasma levels of intermediates of bile acid biosynthesis such as tri- and dihydroxycholestanoic acid were found. Other peroxisomal functions were normal. Immunoblotting of the peroxisomal beta oxidation enzyme proteins in liver from the patient revealed normal responses with antisera against acyl-CoA oxidase, bifunctional protein and thiolase respectively. From these data we conclude that the patient had a deficiency of a single peroxisomal beta-oxidation enzyme at the level of either the bifunctional protein or peroxisomal thiolase with retained immunoreactivity against these enzymes. PMID- 2209667 TI - Surfactant treatment for respiratory distress syndrome following prolonged rupture of membranes. AB - Surfactant replacement for respiratory distress syndrome (RDS) following very prolonged rupture of the membranes (PROM) is of uncertain value. Seven preterm babies born after PROM (median 48 days, range 22-61 days) were compared with 14 babies without PROM. All had clinical and radiological evidence of severe RDS, requiring mechanical ventilation with inspired oxygen concentrations greater than or equal to 60%. Indices of oxygenation and "compliance" were compared before and serially up to 4 h after surfactant treatment. Before treatment the PROM babies had more severe lung disease, based upon higher inspired oxygen concentration and mean airway pressure, and lower arterial/alveolar oxygen tension ratio and ventilator efficiency index. These indices were significantly worse in the PROM group than the comparison group at all times after treatment. The poor response of the PROM group, perhaps because of pulmonary hypoplasia, suggests that surfactant replacement may not be beneficial for RDS in these babies. PMID- 2209668 TI - Cotinine concentrations in amniotic fluid and urine of smoking, passive smoking and non-smoking pregnant women at term and in the urine of their neonates on 1st day of life. AB - Cotinine was measured in the amniotic fluid and urine of 31 pregnant women and in the urine of their offspring. Amniotic fluid cotinine was 8 times higher in active and 2.5 times higher in passive smokers than in non-smokers. In general, amniotic fluid cotinine was considerably higher than urinary cotinine both in active and in passive smokers. Estimation of cotinine both in amniotic fluid immediately before delivery and in urine of the newborn on the 1st day of life aids in assessing the degree of prenatal exposure to tobacco smoke. PMID- 2209669 TI - Parental smoking and asthma in childhood. AB - The effect of parental smoking on childhood asthma was investigated in which data from 302 asthmatic and 433 healthy children aged 1 to 12 years, were studied. All asthmatic patients received prick tests for common allergens. A significantly higher number of heavy parental smokers was found in asthmatic children under 6 years of age with negative prick tests (P = 0.02). A stepwise logistic regression was performed in order to verify interactions between parental smoking and other variables. It is concluded that parental smoking is an important risk factor for "prick test negative" asthmatic children aged 6 years or less. PMID- 2209671 TI - Thyrotoxic encephalopathy and recurrent seizures. AB - Epilepsy is a rare but possible manifestation of thyrotoxicosis. The patient reported here developed recurrent, generalized and focal seizures, as presenting symptoms of a thyrotoxic encephalopathy. Intercritic EEG records showed triphasic waves. Seizures and signs of encephalopathy disappeared and the EEG reverted to normal only after treatment of the thyroid hyperfunction. It is concluded that thyroid function should be evaluated in cases of otherwise unexplained encephalopathy with untreatable seizures and triphasic waves. PMID- 2209670 TI - Loss of dopamine uptake sites labeled with [3H]GBR-12935 in Alzheimer's disease. AB - The binding of the dopamine uptake inhibitor [3H]GBR-12935 to postmortem putamen from a control group and patients with Alzheimer's disease/senile dementia of Alzheimer type (AD/SDAT) or vascular dementia (VD) was studied. The binding density (Bmax) in AD/SDAT was significantly reduced to 50% of control. A reduction of Bmax in VD was also noted, but it did not reach statistical significance. No differences in apparent binding affinity (Kd) between controls and dementia groups were obtained. The concentrations of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT) and homovanillic acid were also determined. The concentrations of DA and DOPAC were reduced by 30 40% in AD/SDAT and VD, but the reductions did not reach statistical significance. The concentration of 3-MT was reduced by 40% in AD/SDAT and by 30% in VD. The [3H]GBR-12935-binding densities correlated significantly with corresponding concentrations of DA in control brains. It is suggested that the loss of [3H]GBR 12935-binding sites in human putamen in AD/SDAT reflects a degeneration of dopamine neurites. PMID- 2209672 TI - Hypotensive effect of long-term levodopa in patients with Parkinson's disease. AB - To study the hypotensive effect of L-dopa in patients with Parkinson's disease on long-term L-dopa, the blood pressure (BP) was measured in 14 patients and 6 controls before 100 mg L-dopa plus decarboxylase inhibitor and for up to 180 min after dosing. Plasma monoamines and motor functions were assessed. The mean BP was reduced between 60 and 180 min after dosing in the patients, whereas such a reduction was not observed in 5 patients from whom L-dopa was withheld and in controls who showed a high ratio of plasma dopamine compared to plasma L-dopa after dosing. The L-dopa-induced reduction in BP was thought to be due to a central nervous mechanism. PMID- 2209673 TI - Prognosis in patients with transient ischaemic attacks and minor stroke associated with a normal angiogram. AB - 61 patients with a transient ischaemic attack (TIA) or minor stroke and a normal angiogram and with no other explanation for the ischaemic event were followed up for a mean period of 6.3 years. Of 19 patients with a TIA 5 suffered further TIAs, and 1 of the 5 also an ischaemic stroke. 3 of 42 patients with a minor stroke had a new ischaemic stroke, in 1 case preceded by a TIA. In 2 stroke patients the lesion affected a new arterial region. 3 patients died of cerebral haematoma, in 1 preceded by an ischaemic stroke. 4 patients suffered myocardial infarction, and 1 of these died. The overall incidence of recurrent cerebral and cardiovascular symptoms was 23% (14 of 61 patients). The mean age was significantly higher (p less than 0.01) in patients with recurrent cerebral and cardiovascular lesions. No correlation emerged between risk factors. Patients with a TIA or minor stroke and a normal angiogram and with no other known source of embolism have a better prognosis than patients with a known source of embolism. However, elderly patients in particular run an increased risk of cardiac and cerebral vascular incidents. PMID- 2209675 TI - Bilateral limb dystonia due to chronic subdural hematoma. AB - Secondary dystonia has been reported in association with a number of pathological processes. For the first time we are presenting a case of bilateral limb dystonia due to chronic subdural hematoma. PMID- 2209674 TI - Cerebrospinal fluid neuropeptide Y in Alzheimer's disease. AB - The cerebrospinal fluid neuropeptide Y level was measured by radioimmunoassay in 20 patients with probable Alzheimer's disease and in 19 controls. The mean level was lower in patients (69.5 +/- 36.7 pg/ml) than in controls (103 +/- 21.8 pg/ml; p less than 0.001). Patients with a disease duration of greater than 2 years had cerebrospinal fluid neuropeptide Y levels lower than those with shorter disease duration (p less than 0.02). These results suggest that neuropeptide Y containing cells may be involved in Alzheimer's disease. No correlation was found between neuropeptide Y levels and degree of cognitive impairment or age at disease onset. PMID- 2209676 TI - Acute carotid artery occlusion--operative or conservative management. AB - 64 ischemic stroke patients with angiographically verified occlusion of the internal carotid artery were studied. 32 patients underwent surgical revascularization in the acute stage within a few hours of acute onset of stroke. 32 patients had conservative management of treatment. Both groups were compared in regard to mortality rate, functional recovery and clinical findings or neurological deficits and psychiatric disturbances on admission and 4 weeks later. Correlations of functional recovery between the two groups showed no significant differences. Mortality rate in the conservatively managed group however was significantly lower than in the operative group. PMID- 2209677 TI - Epilepsy in multiple sclerosis. AB - In a series of 2,353 multiple sclerosis (MS) patients, 40 subjects presented seizures, with an overall prevalence of 1.70%. The prevalence was 2.33% (34/1,459) in definite MS cases, 0.58 in probable cases (3/518), 0.79 in possible cases (3/376). Twenty-six patients were females, 14 were males. In 13 cases, epilepsy had begun before MS onset; in 4 patients, the two diseases started contemporarily; in 23 patients, epilepsy followed MS onset. No relationship was found between frequency of seizures and course of MS nor between frequency of seizures and MS severity. In 12 patients, magnetic resonance imaging was performed: plaques adjacent to the cerebral cortex were found in 3 cases. The electroencephalogram showed paroxysmal discharges in 11 patients (focal in 2, diffuse in 9). Slow theta and/or delta activity was found in 15 patients (focal in 7, diffuse in 6, both focal and diffuse in 2). The EEG was normal in 14 patients. Possible etiological factors other than MS were recognized in 4 patients only: cranial trauma in 3, meningitis in 1. Our study on a large MS population confirms that MS is associated to a risk for epilepsy higher than that of the general population. PMID- 2209678 TI - Cyclosporine versus azathioprine in the treatment of multiple sclerosis: 12-month clinical and immunological evaluation. AB - The aim of this trial was to compare the efficacy and tolerance of cyclosporine A (CYA) and azathioprine (AZA) as long-term immunosuppressive treatment for patients with multiple sclerosis. 31 randomly assigned patients completed a 12 month treatment with either CYA (5 mg/kg/day) or AZA (2 mg/kg/day). Evaluation included serial quantitative clinical assessments and circulating T cell markers. The CYA treatment group improved in only one of three scoring systems (p less than 0.05), while no difference was observed in the AZA group. CYA and AZA did not influence CD4+/CD8+ ratio of circulating T cells but affected HNK-1+ cells. The overall frequency of abnormal laboratory values were comparable in both groups. We conclude that CYA given in a low dose is relatively well tolerated but its benefits appear to be of limited value. PMID- 2209679 TI - High-dose praziquantel for neurocysticercosis: efficacy and tolerability. AB - Standard therapeutic regimens of praziquantel for neurocysticercosis use daily doses of 50 mg/kg for 15-21 days, with prolonged remission being achieved in 60 80% patients. In this prospective study, 100 mg/kg daily was used for 10 days in 13 patients aged 32 +/- 15 years (mean +/- SD) with severe intra-, extra parenchymal or mixed forms of neurocysticercosis. Patients were monitored with computerized tomography and cerebrospinal fluid (CSF) examination on days 1, 5 and 10. Full blood count, sedimentation rate, blood sugar, urea, creatinine, bilirubin, liver transaminases, alkaline phosphatase, urine analysis and electrocardiogram were carried out before and after treatment. Doses of dexamethasone and of other drugs used concomitantly were controlled. There was no toxicity, clinical or detected by the methods employed in the study. After 22 +/- 5 (mean +/- SD) months follow-up, 6 patients needed ventriculoperitoneal shunting, 2 had died, 7 were improved and led useful lives and 4 were in prolonged remission. There was no correlation between serum or CSF praziquantel correlation and outcome of treatment. The proposed regimen is well tolerated, may be as efficient as previously advocated regimens, requires less hospitalization time and may be adopted routinely for therapy of neurocysticercosis. PMID- 2209680 TI - Modifications of cyclic alternating pattern in sleep apnea syndrome. AB - Within non-rapid eye movement sleep, two complementary modalities of arousal organization may be identified: (1) the cyclic alternating pattern (CAP), correlated with successive upward (phase A) and downward (phase B) fluctuations of arousal and arousal-related vegetative functions, and (2) non-CAP, corresponding to a relative stability of arousal and vegetative activities. In a 62-year-old overweight and heavily snoring man, complaining of excessive daytime sleepiness, three consecutive polysomnograms displayed a highly frequent occurrence of nocturnal apneas (apnea index: 15), mostly obstructive and mixed, limited to non-rapid eye movement sleep stages 1 and 2. The apneic episodes, that never occurred during non-CAP, exclusively appeared during the inhibitory phase B of CAP, whereas the following breathing resumption was mainly induced by an activating phase A pattern. The crucial effect of arousal instability on respiratory control is emphasized. PMID- 2209681 TI - Disulfide bridge formation between C1q and IgG in vitro. AB - The globular heads of C1q are known to possess free-SH groups. Here we show that these groups, which are concealed in the native molecule, are exposed by interaction of C1q with dialysis membrane. During iodination, I+ and I2 oxidize these sulfhydryls to produce disulfide-linked C1q aggregates. Approximately 15% of C1q bound to immunoglobulin aggregates is resistant to high conductivity elution and reducing agent is required to release it. These data show that dialysis, adsorption to Ig and iodination of C1q result in structural and functional changes in the molecule, and suggest a mechanism by which these changes occur. Disulfide bridging between C1q and IgG in vitro suggests that this may be a normal physiological function of C1q for which the free cysteines of human, mouse and guinea pig C1q have been conserved. PMID- 2209682 TI - Non-tolerance and differential susceptibility to diabetes in transgenic mice expressing major histocompatibility class II genes on pancreatic beta cells. AB - In insulin-dependent diabetes mellitus aberrant expression of major histocompatibility complex (MHC) class II antigens might induce autoimmune destruction of insulin-producing pancreatic beta cells. Here we demonstrate that already the expression of single MHC class II chains (E alpha k and E beta b) is sufficient to cause diabetes without affecting beta cell morphology and cell numbers. Our transgenes interfere at least in two points of insulin production leading to a severely diabetic phenotype. In one case E beta b expression led to a 10-30-fold decrease of mouse insulin mRNA. In another case E alpha k expression reduced insulin secretion to background levels. In addition, we also found a patchy distribution of both insulin and E alpha k expression, indicating heterogeneity of the beta cell population, without the concomitant development of diabetes. Although the transgenic E alpha k E beta b MHC class II molecules were expressed on the surface of pancreatic beta cells, the transgenic mice did not prove to be tolerant for I-E antigen. Autoimmune reactions remained absent showing that aberrant MHC class II expression on pancreatic beta cells alone is not sufficient for the development of autoimmune diabetes in mice. PMID- 2209683 TI - Anti-immunoglobulin antibodies induce apoptosis in immature B cell lymphomas. AB - WEHI-231 and CH31 are phenotypically immature sIgM+ murine B cell lymphomas whose growth is inhibited by anti-immunoglobulin (Ig) antibodies. These lines have therefore been used as models for studying the role of surface Ig receptors in the induction of B cell tolerance. We show here that anti-mu antibodies induce DNA cleavage into oligonucleosomal fragments characteristic of programmed cell death (apoptosis) in both cell lines, although WEHI-231 cells are less susceptible than CH31. This effect was reversed by lipopolysaccharide, in agreement with the known effects of lipopolysaccharide on anti-Ig-induced growth inhibition. These results therefore indicate that these lymphomas afford a potentially interesting model to study the mechanisms of programmed cell death induced by ligation of the antigen receptors on normal B cells. PMID- 2209684 TI - Accumulation of bromodeoxyuridine-labeled cells in central and peripheral lymphoid organs: minimal estimates of production and turnover rates of mature lymphocytes. AB - Daily lymphocyte production in both central and peripheral lymphoid organs was evaluated by associating in vivo incorporation of bromodeoxyuridine (BrdUrd) with cell surface labeling and multi-parameter flow analysis. At least 10% of mature T and B lymphocytes are generated every 24 h. The kinetic behavior of these cell populations differs, however, in that mature B cells are generated predominantly in the precursor compartments of the bone marrow, while most mature T cell generation occurs at the periphery. Therefore, peripheral expansion is the major mechanism of mature T cell production in the adult mouse. By following the accumulation of BrdUrd-labeled cells in peripheral lymphoid organs we found that the progeny of the daily lymphocyte production was sufficient to renew 30%-40% of all peripheral T and B cells every 48 h, demonstrating a high turnover rate of mature lymphocytes. We also examined the conditions of BrdUrd labeling of cycling cells in vivo. We found that while greater than 90% of bone marrow and thymus cells in S phase were labeled with a single injection of BrdUrd, in peripheral lymphoid compartments 70% of T and B cells in S failed to incorporate BrdUrd. Particular schedules of BrdUrd administration were required to overcome the low labeling efficiency of mature cells in vivo. Prolonged BrdUrd administration, however, had toxic effects on resident cells. The low labeling efficiency of BrdUrd incorporation by mature cells, as well as its potential toxicity during prolonged administration, may explain controversial results obtained by the different strategies used to study lymphocyte population dynamics. PMID- 2209685 TI - Divergency in the specificity of the induction and maintenance of neonatal suppression. AB - Neonatal treatment of BALB/c mice with anti-VHT15 antibodies suppresses serum expression of VHT15 immunoglobulins in adult animals (2 months) which remains for over 8 months in half of the cases. Suppressed mice, however, contain control numbers of B cells expressing genes of the S107VH family and producing VHT15 after mitogenic stimulation. Furthermore, immunization with phosphorylcholine (PC) breaks suppression and stimulates the production of VHT15 anti-PC antibodies. These animals, however, contain no detectable B lymphocytes expressing the T15 idiotype and produce no T15 idiotype-positive antibodies in response to PC. These results are discussed in the context of lymphocyte repertoire selection. PMID- 2209686 TI - Natural killer cells activated with interleukin 2 in vitro can be adoptively transferred and mediate hematopoietic histocompatibility-1 antigen-specific bone marrow rejection in vivo. AB - An adoptive transfer model was developed for examining natural killer (NK) cell mediated bone marrow cell (BMC) graft rejection. Homogeneous populations of NK cells were obtained by culturing spleen cells from mice with severe combined immune deficiency in the presence of recombinant interleukin 2 for 7 days. These cells maintained a phenotypic (CD3-CD4-CD8-NK-2.1+ and asialo GM1+) and lytic pattern consistent with that of activated NK cells. The cells were infused into lethally irradiated recipients whose own NK cells were depleted by anti-NK-1.1 antibody treatment and could no longer reject marrow allografts. The transferred NK cells restored the ability of the hosts to reject BMC in a hematopoietic histocompatibility-1 (Hh-1) antigen-specific manner. Immunogenetic studies demonstrated that the rejection was a function of the donor, not host, NK cells. These studies demonstrate that NK cells can be cultured in vitro with recombinant interleukin 2 and are capable of mediating Hh-1-specific BMC rejection in vivo in the absence of other immune cell types. PMID- 2209687 TI - Structural diversity of Plasmodium falciparum gp200 is detected by T cells. AB - T lymphocyte clones (TLC) specific for P. falciparum gp200 (a glycoprotein precursor of the main merozoite surface component) were obtained from two individuals with past exposure to malaria. The 25 established TLC carried the CD4 antigen and proliferated in the presence of immunopurified gp200, crude lysate of the parasite and intact infected red blood cells. They were further tested in proliferation assays for their capacity to recognize the structural diversity displayed by gp200. The stimulating antigen used in these assays was either sonicated or viable preparations of schizonts from five P. falciparum isolates differing in their gp200. The majority of the TLC proliferated similarly in the presence of each of the isolates. One third of the TLC proliferated to a different extent depending on the isolate used for stimulation, while two clones gave isolate-specific responses. These results indicate that the majority of human TLC raised in vitro against gp200, is directed against common determinants. This also suggests that immunization with full length gp200 will not lead predominantly to T cell help restricted to isolate-specific determinant. PMID- 2209688 TI - Ontogenic characterization of thymic B lymphocytes. Analysis in different mouse strains. AB - We have characterized a population of murine B lymphocytes present in the thymus (TBL). They are a minor subset (0.2%-1% of total thymocytes), present from perinatal periods onwards and constituted by activated cells with a high proportion of Ig-secreting cells. They represent the first B lymphocytes detected that secrete IgG after birth. Functional analysis reveals that the frequency of lipopolysaccharide-responding cells in TBL is 5- to 10-fold lower than in the spleen. TBL from adult mice did not show any significant difference in their VH repertoire expression when compared to peripheral B lymphocytes. Furthermore, we have been able to isolate a subpopulation of B220+IgM-CD3- thymocytes whose putative B cell precursor potential needs to be directly analyzed. These and other findings support the intrathymic resident characteristics of TBL and suggest new ways of elucidating its physiological role in the complex selective processes occurring inside the thymus. PMID- 2209689 TI - Failure to find alloimmune memory in the resorption phenomenon of Botryllus cytomictical chimera. AB - It has been previously shown that mixed-cell chimeras may be established between different colonies of the compound tunicate Botryllus schlosseri given that they share one allele in common on the fusibility locus. However, one of the partners in each chimera is often resorbed. Here we tested for the existence of a memory component to this response, as measured by the accelerated interval to resorption of a second set of semiallogeneic colonies. Eight genetically unrelated colonies gave rise to eighteen chimeras. After a complete resorption of the "inferior" partners in these chimeras, secondary and tertiary sets of chimeras were established with some of them by fusion of the "superior" with naive subclones of the "inferior" partners. It is shown here that (a) when multiple chimeras are prepared using the same pair of colonies, subclones of only one of the partners are resorbed; (b) high variation in the time for resorption is recorded when several chimeras are prepared from any specific pair of colonies, and (c) the time for resorption is not related to the number of vessels connecting between the partners in the chimera, nor to their relative body sizes. Allospecific memory is not documented here and reasons for its absence are discussed. PMID- 2209690 TI - Cellular requirements for anti-DNA production induced in mice by immunization with bacterial DNA. AB - To further define DNA immunization as a model for anti-DNA production, we investigated the cellular requirements for this response in mice immunized with single-stranded DNA from E. coli. The anti-DNA responses of genetically immune deficient mice and congenic controls were measured by ELISA after immunization with E. coli DNA as complexes with methylated bovine serum albumin in complete Freund's adjuvant. T cell-deficient BALB/c-nu/nu mice failed to produce IgG anti DNA by this protocol despite high backgrounds of IgM anti-DNA. In contrast, CBA/N mice expressing the xid defect displayed IgG anti-DNA responses comparable to those of CBA/J mice despite a reduced IgM response; the specificity of CBA/N and CBA/J anti-DNA antibodies was similar as determined by binding to synthetic DNA and RNA antigens. These results suggest that the anti-DNA response stimulated by DNA immunization is dependent on T cells but not the B cell population affected by xid. The intact IgG response of immunized xid mice differs from that of lupus mice bearing xid where this gene defect leads to significant reduction of spontaneous anti-DNA production. PMID- 2209692 TI - Control of primary and secondary antibody responses by cytotoxic T lymphocytes specific for a soluble antigen. AB - BALB/c mice immunized with keyhole limpet hemocyanin (KLH) develop Thy-1+ and CD8+, KLH-specific cytotoxic T cells (Tc). Such Tc cells can lyse TNP-specific B cells activated with TNP-KLH, but not with TNP-ovalbumin. Cytotoxicity was inhibited by anti-H-2K/D antibodies, but not by anti-Ia antibodies, suggesting a major histocompatibility complex class I-restricted killing. Selective enrichment for virgin and memory TNP-specific B cells revealed that the latter cells were relatively resistant to lysis by KLH-specific Tc cells. Depletion of CD8+ T cells from cultures of TNP-specific virgin B cells activated with TNP-KLH and KLH primed T cells, increased the titer of anti-TNP antibodies in the culture supernatants. This increase was reduced if KLH-primed CD8+ T cells were added to the culture 1 day before its termination. Anti-TNP antibody secretion by memory B cells activated in the same manner was not affected by depletion or addition of CD8+ cells. These results suggest that Tc cells are generated following immunization with a soluble antigen which may participate in the down-regulation of primary B cell responses. PMID- 2209691 TI - Autoantibody production by severe combined immunodeficient mice reconstituted with synovial cells from rheumatoid arthritis patients. AB - In an attempt to characterize the heterogeneity of the human autoantibody response, mice with severe combined immunodeficiency were reconstituted with synovial or blood lymphocytes from patients with rheumatoid arthritis (RA). Mononuclear cells extracted from synovial fluid or tissue (SMC) were a greatly enriched source of IgM rheumatoid factor (RF)-producing cells compared to the peripheral blood mononuclear cells (PBMC) of rheumatoid arthritis patients or normal donors. Six to nine weeks after reconstitution of mice with synovial mononuclear cells, 0%-39.3% (mean = 11.4%) of total IgM consisted of IgM RF compared to 0%-0.15% (mean = 0.02%) in mice given RA PBMC and 0%-1.2% (mean = 0.34%) in mice given normal PBMC. Detectable levels of IgM RF were maintained in some mice for as long as 20 weeks after transfer. Mice reconstituted with synovial membrane or synovial fluid lymphocytes produced a heterogeneous mixture of immunoglobulins. These included other autoantibodies, such as anti-nuclear and anti-cytoplasmic antibodies, and antibodies to exogenous antigens such as the Epstein-Barr virus nuclear antigen-1 (EBNA-1). This heterogeneity is further illustrated by the demonstration that the sera from mice given synovial cells also contained IgG antibodies possessing all three major VH families (VH1, VH3 and VH4) and the four major V kappa families (V kappa 1 to V kappa 4). Autoantibody production gradually decreased with time even under circumstances where total immunoglobulin levels increased, and elevated production could not be induced by antigenic stimulation. These findings describe a new model for the analysis of human autoantibody production. PMID- 2209693 TI - Antigens recognized on a melanoma cell line by autologous cytolytic T lymphocytes are also expressed on freshly collected tumor cells. AB - Peripheral blood lymphocytes of a melanoma patient were stimulated in vitro with a permanent cell line derived from the autologous tumor. Stable cytolytic T lymphocyte (CTL) clones were obtained that lysed the melanoma cell line and did not lyse autologous Epstein-Barr virus-transformed B lymphocytes or K-562 cells. These CTL clones were directed against two distinct antigens on the melanoma line. In view of the possibility that these antigens could be culture artefacts, we tested the stimulatory ability of tumor cells that had been freshly collected from metastatic relapses on the CTL clones. A considerable CTL proliferation was observed and it appeared to be specific. We conclude that the antigens recognized by the autologous CTL clones on the permanent melanoma cell line were expressed by the tumor cells in the patient. PMID- 2209694 TI - Quantitative changes in T cell DNA methylation occur during differentiation and ageing. AB - DNA methylation is one of the mechanisms involved in the regulation of developmentally relevant genes. Previous experiments demonstrated that T cells treated with DNA methylation inhibitors reacquire some of the phenotypic and functional characteristics of thymocytes, suggesting that DNA methylation may be involved in regulating some of the changes in gene expression during thymic maturation. To further examine whether changes in DNA methylation occur during T cell differentiation, total DNA deoxymethylcytosine content was compared in human thymocyte subsets and mature T cells. A significant increase in deoxymethylcytosine was found at the end of T cell differentiation which then decreased with age. These results suggest that increased DNA methylation may serve to silence genes following T cell differentiation. The results also raise the possibility that age-related decreases in T cell DNA methylation may contribute to changes in T cell function occurring in the elderly. PMID- 2209695 TI - Dual effects of interleukin 4 on antigen-activated human B cells: induction of proliferation and inhibition of interleukin 2-dependent differentiation. AB - We analyzed the effects of interleukin 2 (IL 2) and IL 4 isolated and in association on the specific response of human B cells triggered by trinitrophenylated polyacrylamide beads (TNP-PAA). IL 2 induced an increase (more than 10 times) in the number of hapten-binding cells [detected by a rosette forming cell (RFC) assay] as well as the generation of antibody-producing cells [detected by a plaque-forming cell (PFC) assay]. IL 4 induced an isolated RFC response without PFC response. We verified that the IL 4 (as well as 12)-induced RFC were hapten specific and mediated through membrane IgM. Density fractionation experiments showed that IL 4-induced RFC were equally distributed between high density and intermediate-density B cells. IL 2 appeared to drive more B cells into the intermediate density fraction. IL 2-induced PFC belonged to the RFC population and were intermediate-size B cells. IL 2 drove more RFC into an activated stage and it induced the differentiation of a number of them into antibody-producing cells. The evaluation of the proportion of RFC able to incorporate thymidine showed that both IL induced a substantial proliferation of antigen-activated B cells. However, IL 4 inhibited the IL 2-dependent PFC without affecting the number of RFC nor the proportion of proliferating RFC induced by this IL. These results directly demonstrate that human IL 4 triggers the expansion of antigen-activated B cells and selectively inhibits the IL 2-induced differentiation. PMID- 2209696 TI - Abnormal behavior of gamma-committed B lymphocytes probed by a lymphocyte blastogenesis inhibitory factor in autoimmune MRL mice. AB - Recently, we have characterized a lymphocyte blastogenesis inhibitory factor (LBIF) which was purified from the culture supernatant of a human histiocytic lymphoma U-937 (Sugimura, K. et al., Eur. J. Immunol. 1989. 19: 1357). In this study, we investigated the effect of LBIF on the antibody production of autoimmune MRL mice in vitro. We demonstrated here that (a) LBIF inhibited the IgM, IgG and IgA antibody responses of lipopolysaccharide (LPS)-stimulated spleen cells of normal BALB/c mice, (b) in the case of old autoimmune MRL/Mp-lpr/lpr (MRL/l) and MRL/Mp-(+)/+ mice, however, LBIF inhibited IgM and IgA but not IgG responses of LPS-stimulated spleen cells, (c) the antibody production of all IgG subclasses, IgG3, IgG1, IgG2b and IgG2a, was not sensitive to LBIF inhibitory activity in these autoimmune mice, (d) in young MRL mice (3-5-week-old MRL/l), which were phenotypically normal, LPS-induced antibody production of all isotypes (IgM, IgG and IgA) was strongly inhibited by LBIF as shown in normal BALB/c mice and (e) in the case of 7-week-old MRL/l the insensitivity to LBIF was concomitant with the appearance of gamma + B lymphocytes. Thus, by employing LBIF as a probe, this study showed a correlation between the pathogenesis of MRL autoimmune disease and the lack of LBIF sensitivity of hyperactive B lymphocytes and suggested that the intrinsic abnormality of autoimmune MRL B lymphocytes might be confined to gamma- but not mu- or alpha-committed B cells. PMID- 2209697 TI - Binding of toxic shock syndrome toxin-1 to murine major histocompatibility complex class II molecules. AB - The staphylococcal exotoxin toxic shock syndrome toxin-1 (TSST-1) has potent stimulatory effects on murine and human lymphocytes. This is the consequence of TSST-1 binding to major histocompatibility complex (MHC) class II molecules and the engagement in a V beta-restricted fashion of the T cell receptor by the TSST 1-MHC class II complex. Using radioligand and functional assays we have recently shown that TSST-1 binds to all HLA-DR (n = 14), HLA-DQ (n = 2) and HLA-DP (n = 2) phenotypes tested. In this study, we have examined the ability of murine MHC class II molecules to bind TSST-1. Specific high-affinity binding of TSST-1 was detectable to unfractionated BALB-c (H-2d) and C57BL/6 (H-2b), but not to C3H (H 2k) spleen cells. The Kd of this binding estimated from Scatchard analysis was in the same nanomolar range as the Kd of binding of TSST-1 to HLA-DR. Binding of 125I-labeled TSST-1 to BALB/c-derived B cell lymphoma lines and to L cell transfectants correlated with the expression of I-A molecules, but not with the expression of I-E molecules. Furthermore, I-A+, I-E- cells but not I-A-, I-E+ cells were able to support TSST-1-induced T cell proliferation. The binding affinity of TSST-1 for I-Ak appears to be much lower than for I-Ad. L cell transfectants expressing hybrid DR alpha: I-E beta k molecules, but not those expressing I-E alpha k: DR1 beta molecules, could bind TSST-1 and efficiently support TSST-1-induced T cell proliferation. This suggests that minor differences in the highly homologous I-E alpha and DR alpha chains are critical in determining the affinity of the MHC class II molecule for TSST-1. These results demonstrate that the binding of TSST-1 to MHC class II molecules in the mouse, in contrast to humans, is strongly influenced by phenotype. Analysis of the molecular basis of these differences may help to localize staphylococcal exotoxin binding sites on MHC class II molecules. PMID- 2209698 TI - Resistance to lymphoid engraftment in lpr recipients of normal bone marrow: characterization of chimeric stem cell, monocyte and peripheral lymphoid lineages. AB - Lethally irradiated MRL/lpr mice reconstituted with T cell-depleted bone marrow stem cells from the non-autoimmune strain A. Thy had been shown to develop a state of long-term split chimerism; erythrocytes were derived from the A. Thy donor, while peripheral lymphocytes were derived from the lpr recipient. In contrast, recipients of the non-lpr-congenic strain, MRL/+, were fully repopulated in both lineages by donor-derived hematopoietic cells. In order to more fully understand the mechanisms responsible for this type of split chimerism, we have investigated additional genetic and developmental parameters. We found that histocompatible normal B cell precursors engrafted C3H/HeJ and C57BL/6/+ mice much better than they engrafted the corresponding lpr congenic strains, indicating that resistance to lymphoid engraftment was not unique to the MRL background. Bone marrow cells and peritoneal macrophages were found to express the donor H-2 phenotype in both non-lpr and lpr recipients, limiting resistance to the lymphoid lineage. Moreover, we showed that normal bone marrow stem cells passaged in an lpr host environment were subsequently able to repopulate the B cell lineage of non-lpr secondary recipients, proving that prelymphoid stem cells were intact. Although lymph node cells from A. Thy--- MRL/lpr chimeras were lpr-derived, they did not show the abnormal surface marker expression associated with the lpr phenotype, nor did they develop lymphoid hyperplasia or elevated autoantibody levels. However, A. Thy----MRL/lpr chimeras differed from normal mice in that their spleens were markedly deficient in IgM+ B cells. PMID- 2209699 TI - Interleukin 6 is a differentiation factor for human megakaryocytes in vitro. AB - The response of cells of the megakaryocytic lineage to interleukin 6 (IL6), a cytokine with multiple biological activities, was studied by adding the factor to human bone marrow (BM) cultures. IL6 alone had no effect on megakaryocytic colony formation in methylcellulose; however, in the presence of maximally stimulating concentrations of IL 3, almost a twofold increment in colony formation was observed. Tritiated thymidine suicide studies of BM incubated for 2 h with growth factors showed that almost one-half of megakaryocytic progenitors (CFU-Mk) preincubated with IL3 or IL3 plus IL6 were in S phase, whereas BM incubated with IL6 alone was similar to control (approximately 24% of CFU-Mk in S phase). When greater than or equal to 1 ng/ml of IL6 was added to liquid suspension cultures of BM, the size of individual megakaryocytes was significantly augmented compared with that seen in control cultures. Moreover, the DNA content of megakaryocytes grown in the presence of IL6 was increased (modal ploidy 16N) compared with cultures grown with IL3 (modal ploidy 8N). To determine if the effect of IL6 could be direct rather than mediated via accessory BM cells, the factor was added to cultures of isolated single megakaryocytes. Seventy-one percent of cells increased in diameter in the presence of IL6, while only 27% increased in size in the absence of the factor. The data show that IL6 is a direct maturation factor for human megakaryocytes, promoting increments in size and ploidy of these cells. PMID- 2209700 TI - Mast cell heterogeneity: two-dimensional gel electrophoretic analyses of rat peritoneal and intestinal mucosal mast cells. AB - Peritoneal mast cells (PMC) and intestinal mucosal mast cells (IMMC) were purified from rats infected with the nematode Nippostrongylus brasiliensis. Overall protein constituents of both mast cell subtypes were analyzed by two dimensional gel electrophoresis using either nonequilibrium pH gradient electrophoresis (NEPHGE) or isoelectric focusing (IEF) in the first dimension and SDS-PAGE (10%) in the second dimension followed by silver staining. PMC had seven dominant basic proteins (PB2-8; pI 9-9.5) with estimated molecular masses of 26 to 37 kDa, as well as 80 to 90 neutral or acidic proteins, most of which had pI 6 to 7.5 and estimated molecular masses of 20 to 100 kDa. All the basic proteins were granule-associated. Three basic proteins, PB6 (29 kDa), PB7 (28 kDa) and PB8 (RMCP I, 26 kDa), bound [3H]diisopropyl fluorophosphate (DFP), suggesting that they are serine proteases. However, only PB8 was reactive with antibodies to RMCP I. Another basic component (less than 14 kDa), perhaps a degradation product of PB6, PB7 or PB8, also bound [3H]DFP. By comparison, IMMC possessed nine basic proteins (IB1-9) and, in general, they were more acidic (pI about 8.5-9) than those of PMC. Four major basic proteins (IB6-9) were all 24 kDa but were slightly different in isoelectric points. These and another 46-kDa basic component (IB2) were reactive with antibodies to RMCP II and bound [3H]DFP. There were no other DFP-binding proteins in IMMC. In spite of remarkable differences between basic granule-associated proteins in PMC and basic proteins in IMMC, spots in the neutral-acidic range were for the most part similar in the two mast cell subsets, although quantitative differences were evident for some spots. Thus, rat mast cell populations from the peritoneal cavity and intestinal mucosa exhibit marked heterogeneity in their protein constituents with basic pI, including in their granule-associated proteins with serine protease activity. PMID- 2209701 TI - Characterization of the interleukin 5-reactive splenic B cell population. AB - The characteristics of the interleukin (IL) 5-reactive splenic B cell population of C57BL/6 nu/nu mice, with respect to IL 5/IL2 reactivity, cell surface phenotype, VH gene family usage, autoreactivity and the structure of the IL5 receptor (IL5R), were analyzed. It was found that 2%-4% of splenic B cells express relatively high levels of IL 5R as determined by the binding of the anti IL 5R monoclonal antibody R52.120. Over 90% of the splenic B cells that mature to IgM secretion upon activation with IL5 are comprised in this small subpopulation of B cells. Moreover, the vast majority of splenic B cells that mature to IgM secreting cells when activated by IL2 also reside in this IL5R+B cell population. The cell surface phenotype of the IL5R+ splenic B cells is IgM+, B220+, Ly-1- and IL2R p55-. Upon activation with IL5 this cell surface phenotype changes, in that a vast majority of the B cells then express the p55 chain of the IL2R, whereas the level of IL5R decreases. VH gene family usage in the IL5-activated splenic B cells was analyzed by in situ hybridization. VH gene family usage was found to be random and not different from the VH genes expressed in LPS-activated B cells. Hybridoma collections from IL5-activated splenic B cells and LPS-activated B cells were screened and compared for the production of autoantibodies and antibodies directed against the haptens (4-hydroxy-3-iodo-5-nitrophenyl)acetyl (NIP) and 2,4,6-trinitrophenyl (TNP). In both collections high, but not significantly different frequencies of autoantibody-(32% IL5, 31.4% LPS) and of anti-hapten antibody (27.8% IL5, 18.6% LPS)-producing hybridomas were found. The structure of the IL5R on IL5-activated B cells was analyzed by 125I-labeled IL5 binding and cross-linking. About 100 high-affinity (10(-11) M) and 1000 low affinity (10(-9) M) IL5-binding sites are present on IL5-activated splenic B cells, and both high- and low-affinity IL5R are similar to those expressed on the IL5-dependent B13 cell line. Cross-linking of 125I-labeled IL5 to the receptors on IL5-activated B cells revealed one major IL5-binding protein of 45-50 kDa molecular mass and another minor binding protein of 130-140 kDa. The same IL5 binding proteins are present on the IL5-dependent B13 cell line.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2209702 TI - The requirement of intrathymic mixed chimerism and clonal deletion for a long lasting skin allograft tolerance in cyclophosphamide-induced tolerance. AB - Mechanisms of cyclophosphamide (CY)-induced tolerance were studied. When C3H/He Slc (C3H; H-2k, Mls-1b) mice were primed i.v. with 1 x 10(8) viable spleen cells from H-2-identical AKR/J Sea (AKR; H-2k, Mls-1a) mice and treated with 200 mg/kg of CY 2 days later, a long-lasting skin allograft tolerance to AKR was established. When [C57BL/6 Sea (B6; H-2b, Mls-1b) x AKR]F1 (B6AKF1) cells were used as the tolerogen, however, only a moderate, but not long-lasting, skin tolerance to AKR was observed. In the C3H mice treated with AKR cells and CY, the intrathymic clonal deletion of V beta 6+ T cells, which are strongly correlated with reactivity to Mls-1a antigens, was observed in the chimeric thymus on day 35, although neither the clonal deletion of V beta 6-bearing T cells nor the mixed chimerism was observed in the thymus on day 14. In the C3H mice treated with B6AFKF1 cells followed by CY, however, neither the clonal deletion of V beta 6+ T cells nor the mixed chimerism was observed in the thymus throughout the test period. In the lymph nodes of the C3H mice treated with AKR cells and CY, only CD4+ V beta 6+ T cells, bur not CD8+V beta 6+ T cells, had selectively decreased by day 14, and they were hardly detectable on day 35. The selective decrease of CD4+V beta 6+ T cells in the lymph nodes was also observed by day 14 when B6AKF1 cells were used as the tolerogen, although CD4+V beta 6+ T cells gradually increased on day 35, at which time almost all skin grafts from AKR had already been rejected. These results strongly support the necessity of the intrathymic mixed chimerism and clonal deletion of donor-reactive T cells for a long-lasting skin allograft tolerance in CY-induced tolerance. PMID- 2209703 TI - Bone marrow transplantation from mutant lpr/lpr mice. Functional abnormalities rather than alloantigenic differences appear to determine the development of a graft-vs.-host-like syndrome. AB - Transfer of bone marrow (BM) from autoimmunity-prone mice homozygous for the lymphoproliferation (lpr) mutation to irradiated congenic +/+ recipients has previously been shown to result in a syndrome similar to chronic graft-vs.-host (GVH) disease. It has been suggested that this syndrome may be due to an antigenic difference caused by the lpr mutation itself or to antigenic differences at loci closely linked to the lpr locus (Theofilopoulos, A. N. et al., J. Exp. Med. 1985. 162:1; Mosbach-Ozmen, L. and Loor, F., Thymus 1987. 9:197). However, the results presented here indicate that alloantigenic differences do not play a role in this syndrome. Instead, the chronic disease observed in lpr/lpr----(+/+) BM chimeras appears to develop as a result of a functional defect associated with the lpr mutation which is expressed shortly after transfer of lpr/lpr BM to irradiated recipients. This defect causes an increase in the levels of serum IgG1 and IgG2, which peak at 4-5 weeks post transfer and then decline to normal levels by 9-10 weeks post-transfer. Inflammation similar to that observed in classic GVH reactions accompanies excess IgG production in congenic +/+ recipients but not in lpr/lpr recipients of lpr/lpr BM. We demonstrate that the GVH-like response occurring in lpr/lpr--- (+/+) chimeras is dependent on mature T cells, but that either lpr/lpr or (+/+) T cells can support this reaction. These results suggest that transfer of lpr/lpr BM to normal mice causes immunoregulatory disturbances which lead to nonspecific activation of T cells. We speculate that lpr/lpr BM causes a GVH-like reaction in +/+ recipients but a systemic lupus erythematosus-like syndrome in lpr/lpr recipients because of intrinsic differences in the +/+ and lpr/lpr host environments. Considering these findings, the lpr/lpr----+/+ GVH model may be useful for analysis of factors capable of inducing undesirable reactions in clinical BM transplantation between nominally histocompatible donors and recipients, in addition to being informative about the nature of the lpr mutation itself. PMID- 2209704 TI - Tolerance to experimental contact sensitivity induced by T cell vaccination. AB - It was shown previously that experimental autoimmune diseases could be prevented or treated specifically by administering suitably attenuated autoimmune T lymphocytes to animals, a process termed T cell vaccination (Cohen, I. R., Sci. American 1988. 256: 52). We now report that T cell vaccination is an effective way of inducing tolerance to contact sensitivity to simple chemical haptens. Vaccines were prepared from populations of lymph node cells from specifically sensitized mice by activating the T cells with the T cell mitogen concanavalin A and then treating the T cell blasts with glutaraldehyde. The vaccinated mice showed decreased delayed sensitivity responses to the specific sensitizing antigen and developed significant delayed sensitivity responses to the T cells of the same specificity as those used for vaccination. Thus, T cell vaccination against contact sensitivity reactions appears to function similarly to T cell vaccination against autoimmune disease. PMID- 2209705 TI - Idiotypic interactions between normal human polyspecific IgG and natural IgM antibodies. AB - Pooled normal human polyspecific IgG (IVIg) contain anti-idiotypes against a variety of autoantibodies from patients with autoimmune diseases and IgG autoantibodies present in IVIg. The present study indicates that IVIg may also react through idiotypic/anti-idiotypic interactions with human natural IgM antibodies. Sixty-four percent of IgM secreted by B lymphoid cell lines derived from B cells of healthy elderly donors and 18% of IgM secreted by cloned EBV transformed cord B cells that were tested, bound through their variable region to F(ab')2 fragments of IVIg. The binding to 2,4,6-trinitrophenyl (TNP) of a polyreactive IgM with anti-TNP specificity, was inhibited by F(ab')2 fragments from IVIg, indicating the presence in IVIg of anti-idiotypes that may interfere with the antibody-combining site of polyreactive IgM antibodies. The ability of IgM antibodies to interact with idiotypes on IVIg was not related to the degree of polyreactivity of natural antibodies. Our observations further document that IVIg contain antibody specificities against Ig from normal individuals and suggest that IgG originating from the physiologically expressed repertoire may modulate the expression of the potential B cell repertoire. The results may be relevant to the suppressive effect of IVIg in autoimmune diseases. PMID- 2209706 TI - Structures on the I-A molecule predisposing for susceptibility to type II collagen-induced autoimmune arthritis. AB - The susceptibility to type II collagen (CII)-induced arthritis (CIA) in mice is profoundly influenced by major histocompatibility complex (MHC) class II genes in the H-2 region. Analyses of MHC-congenic strains on the B10 background show that only strains developing an anti-CII antibody response after immunization with autologous CII develop arthritis after induction with CII from various species. The susceptible haplotypes have been found to be H-2q, H-2r, H-2w3 and H-2w17. In addition, these haplotypes respond to different patterns of CII derived from various species suggesting that T cell receptors and CII peptides interact. In contrast, certain haplotypes closely related to H-2q, such as the H-2p and H-2w5 haplotypes, are resistant to induction of CIA and are nonresponders to CII. We have earlier shown that a critical structure on the I-A beta molecule determines the susceptibility differences between the p and q haplotypes. We have now determined the structure of exon 2 of the A beta as well as some of the A alpha genes of the remaining haplotypes in the p, q and r families. The sequences show similarities between the CIA-susceptible haplotypes in the A beta C-terminal part and the A alpha N-terminal part of the first domains forming a large part of the antigenic peptide-binding site. Among the wild mouse-derived haplotypes, the w5 haplotype showed an A beta sequence identical to that of the p haplotype consistent with its nonresponder nature to CII immunization. These findings suggest that (a) structures shared between different class II molecules are of importance for the susceptibility to disease in mouse strains and (b) most likely recognition of different CII peptides is important for development of disease. PMID- 2209707 TI - Detection of interleukin 8 biological activity in synovial fluids from patients with rheumatoid arthritis and production of interleukin 8 mRNA by isolated synovial cells. AB - The presence of neutrophils in the synovial joint of patients with rheumatoid arthritis (RA) is thought to be due to the activity of chemotactic factors released by activated cells in the joint. We have shown in this report, for the first time, the abundance of one such factor, interleukin 8 (IL 8), in the synovial fluid of patients both with RA and other non-RA joint diseases, and the spontaneous production of IL 8 mRNA by RA synovial cells in culture. There was no correlation between the levels of chemotactic activity and IL 8 protein, suggesting that other factors with similar neutrophil chemotactic activity are also present in the synovial fluid exudate. In support of this concept neither the level of chemotactic activity nor IL 8 protein levels correlated with neutrophil or leukocyte infiltration, indicating that the mechanism of migration into the inflammatory environment of the joint is complex. Such migration is likely to be due to a number of chemotactic signals in addition to IL 8, which may either synergize with, or inhibit, the action of IL 8. PMID- 2209708 TI - Exposure of female mice to type II collagen reduces susceptibility to collagen induced arthritis in offspring. AB - The effect of exposure of female DBA/1 mice to collagen II (CII) prior to breeding on the susceptibility of their offspring to CII-induced arthritis (CIA) was investigated. It was found that female offspring, born within 3 months after exposure of the mothers to CII, had a significantly reduced incidence of CIA, following immunization with CII. Just prior to this immunization, no anti-CII could be detected in the offspring. Offspring born more than 3 months after exposure of the mothers to CII showed no differences in susceptibility to induction of CIA, if optimal conditions for induction were used. However, when suboptimal conditions for induction of CIA were used, offspring of females that had been exposed to CII developed less severe arthritis and had a delayed onset of arthritis as compared with controls. It is concluded that exposure of female mice to CII prior to mating results in changes in the immune response to CII in the offspring, leading to a subtle decrease in susceptibility to CIA. PMID- 2209709 TI - Apparent vascular to cardiac sympatholytic selectivity of omega-conotoxin GVIA in the pithed rat. AB - The effects of omega-conotoxin GVIA (omega-CTX), a blocker of N-type voltage operated calcium channels (VOCCs), were investigated in the pithed rat, omega-CTX (1.6 and 3.2 micrograms/kg i.v.) did not alter resting diastolic pressure or heart rate nor the pressor and chronotropic responses to noradrenaline injections (0.1-10 micrograms/kg). In contrast, the pressor responses to electrical stimulation of the whole spinal cord (0.2-6.4 Hz) were dose dependently reduced by omega-CTX whereas the concomitant tachycardia was less affected. When selective stimulation of the cardiac sympathetic outflow was applied, the resulting chronotropic response was more sensitive to omega-CTX. This result is discussed in the light of the possible interference of adrenal catecholamine release during whole spinal cord stimulation which is not sensitive to omega-CTX. These results provide in vivo evidence that omega-CTX is able to reduce sympathetic neurotransmission to the vasculature and the heart, presumably by blocking N-type VOCCs on pre- and post-ganglionic nerve terminals. PMID- 2209710 TI - Voltage-dependent action of valproate on potassium channels in frog node of Ranvier. AB - The influence of the anti-epileptic drug, valproate, on K conductance (gK) was investigated in voltage-clamped Ranvier nodes of Xenopus laevis. A double pulse method was used in order to eliminate the effect of accumulation of potassium ions in the perinodal space, thus enabling the determination of the 'true' magnitude of gK. Valproate (2.4 mM) had a voltage-dependent action on the magnitude of gK. With small step depolarizations more negative than about -50 mV, valproate increased gK (20 ms after the step) to approximately 12% of the maximal gK, an increase which disappeared due to a relatively rapid (less than 200 ms) inactivation process. However, with step depolarizations more positive than about -50 mV, valproate markedly reduced gK (20 ms after the step) at greater depolarizations, with a maximum of about 40% of the maximal gK. Moreover, at these voltages gK was inactivated completely (less than or equal to 10 s), whereas under control conditions the inactivation was only partial. Both the temporary increase and the steady state decrease of gK could contribute to an anti-epileptic effect by increasing the action potential threshold and by preventing excessive depolarizations of the nerve during epileptic seizures, respectively. PMID- 2209711 TI - Effect of delapril hydrochloride on angiotensin II release from isolated rat hind legs. AB - The effect of the newly developed angiotensin-converting enzyme (ACE) inhibitor, delapril hydrochrolide (CV-3317), on the release of immunoreactive angiotensin II (irAng II) from isolated rat hind legs was compared with that of captopril. Both ACE inhibitors, added to the perfusion medium (2 X 10(-9) - 10(-6) M), suppressed irAng II release in a dose-dependent manner, but the inhibition was greater with delapril than with captopril. The results provide further support for the concept that vascular tissues produce Ang II and release it in a regulated fashion. The results also suggest a possible link between the antihypertensive mechanism of ACE inhibitors, including delapril, and the suppression of vascular Ang II release. PMID- 2209712 TI - A new H-oxime restores rat diaphragm contractility after esterase inhibition in vitro. AB - Acetylcholine esterase inhibitors block cholinergic neurotransmission. This blockade can be reversed by oximes. However, a universally effective esterase reactivator does not exist. A new H-oxime, HLo 7, was tested on rat diaphragm strips. Electrically evoked contractions were blocked by di-2-propyl fluorophosphate (DFP), tabun, sarin and soman. Whereas pralidoxime, obidoxime and HI 6 reversed the blockade induced by three of these organophosphorus compounds, HLo 7 restored the contractions after short blockade induced by all four organophosphorus compounds tested. PMID- 2209713 TI - Actions of forskolin and isoprenaline on the separated myometrial layers of the guinea-pig uterus: influence of ovarian steroids and pregnancy. AB - Responses to forskolin and isoprenaline of electrically stimulated preparations of longitudinal and circular myometrium were compared. The guinea-pigs used were: untreated (dioestrous), ovarian steroid-treated, pregnant and post-partum. Forskolin inhibited electrically evoked contractions of both myometrial layers obtained from all groups; there was no change in its potency or its maximum effect (90-100% inhibition). The inhibition of contractions of longitudinal myometrium by isoprenaline was enhanced with steroid treatment, attaining a maximum in late pregnancy and immediately post-partum. In circular myometrium, there was no significant change in the potency of isoprenaline on tissues from ovarian steroid-treated animals. However, maximum potency as well as maximum response was observed in late pregnancy. Since the effects of isoprenaline but not of forskolin were modulated, we suggest that ovarian steroids and pregnancy may alter the coupling of beta-adrenoceptors to the adenylate cyclase system. PMID- 2209714 TI - Clozapine fails to prevent the development of haloperidol-induced behavioral hypersensitivity in a cotreatment paradigm. AB - We have previously established that chronic cotreatments involving antimuscarinic agents and haloperidol attenuate the development of behavioral hypersensitivity without affecting dopamine receptor proliferation. The antipsychotic agent clozapine also has significant antimuscarinic activity and was coadministered with haloperidol in rats for 2 months to determine if it would similarly attenuate the development of hypersensitivity. Clozapine or chlorpromazine cotreatment, unlike thioridazine cotreatment, did not attenuate the development of haloperidol-induced behavioral hypersensitivity. Clozapine or thioridazine cotreatment also failed to prevent the development of haloperidol-induced D2 receptor proliferation, whereas chlorpromazine cotreatment enhanced D2 receptor proliferation relative to haloperidol-treated animals. Alterations in dopamine biochemistry in the striatum or nucleus accumbens could not explain this dissociation between behavioral hypersensitivity and dopamine receptor proliferation. It is therefore hypothesized that dopamine receptor proliferation is permissive for behavioral hypersensitivity and that factors in addition to alterations in dopamine function contribute to the expression of dopamine hypersensitivity states. PMID- 2209715 TI - Enhancement in gastric mucus gel qualities with colloidal bismuth subcitrate administration. AB - The effects of intragastric administration of an antiulcer drug, colloidal bismuth subcitrate, on the content, composition and physical properties of the mucus component of gastric mucosal barrier were investigated. The experiments were conducted with two groups of rats in which one group received twice daily for three consecutive days a dose of 100 mg/kg colloidal bismuth subcitrate, while the control group received saline. The animals were killed 16 h after the last dose, their stomachs dissected and the mucosa subjected to physicochemical measurements. The results revealed that colloidal bismuth subcitrate elicited a 49% increase in mucus gel dimension, while sulfo- and sialomucin content of the gel increased by 64 and 112%, respectively. The changes in mucus with colloidal bismuth subcitrate were accompanied by a 28% increase in H+ retardation capacity, 2.2-fold increase in viscosity, and a 26% increase in the gel hydrophobicity. The mucus elaborated in the presence of colloidal bismuth subcitrate exhibited 16% lower protein content and 68% higher content of carbohydrate than that of the control, displayed similar levels of total lipids and covalently bound fatty acids, but its phospholipid content was 32% higher. Furthermore, the mucus of the colloidal bismuth subcitrate group showed a marked increase in the proportion of the high molecular weight form of mucin. The results suggest that colloidal bismuth subcitrate is capable of the enhancement of mucus gel qualities associated with the maintenance of gastric mucosal integrity. PMID- 2209716 TI - Mitogen response and cell cycle kinetics of Swiss 3T3 cells in defined medium: differences from human fibroblasts and effects of cell density. AB - The mitogen requirement and proliferative response of Swiss 3T3 cells in serum free, chemically defined culture medium were compared with those of early-passage human diploid fibroblasts. The effects of platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin, transferrin, and dexamethasone on cell cycle parameters were measured using 5'-bromo-deoxyuridine-Hoechst flow cytometry. Swiss 3T3 cells differ from human fibroblasts in several ways: (1) Swiss 3T3 cells showed a much higher dependence on PDGF than human fibroblasts; the growth of the latter, but not of the former, could be stimulated by the combination of EGF, insulin, and dexamethasone to the full extent of that when PDGF was present; (2) in the absence of PDGF, insulin was an absolute requirement for Swiss 3T3 cells to initiate DNA synthesis, while a substantial proportion of human fibroblasts could enter DNA synthesis without exogenous insulin or IGF-I; and (3) in the absence of PDGF, increasing insulin concentration increased the cycling fraction of Swiss 3T3 cells without an appreciable effect on the rate of cell exit from G0/G1, while under similar culture conditions, insulin showed its major effect on regulation of the G1 exit rate of human fibroblasts, without much effect on the cycling fraction. In addition, the proliferative response of high density versus low-density, arrested Swiss 3T3 cells showed that the interaction of mitogens varied with cell density. At high cell density, the PDGF requirement was consistent with the "competence/progression" cell-cycle model. This growth response was not seen, however, when cells were plated at low density. PMID- 2209717 TI - Analysis of nuclear sugar-binding components in undifferentiated and in vitro differentiated human promyelocytic leukemia cells (HL60). AB - The nuclear sugar-binding components (i.e., lectin-like molecules) were analyzed using isolated and membrane-depleted nuclei after incubation in the presence of fluorescein-labeled neoglycoproteins. This analysis was performed before and during the in vitro differentiation of HL60 cells into monocytes by PMA treatment and into granulocytes by DMSO treatment. The nucleoli of undifferentiated and differentiated HL60 cells were not labeled, unlike the nucleoli of other mammalian cells studied so far. This peculiarity allowed us to quantitatively analyze by flow cytometry the changes in the lectin activity associated with the extranucleolar territories enriched in ribonucleoprotein complexes. The neoglycoprotein binding was found to be significantly lower in differentiated than in undifferentiated cells. The decrease in neoglycoprotein binding was observed within the first 24 h of DMSO or PMA treatment, just before the arrest of DNA synthesis. Taking into account that the granulocytic differentiation required 72 h of chemical treatment, the extra-nucleolar lectins might be involved in modulation of the DNA synthesis rather than in phenotypic differentiation. These data are discussed in an attempt to reconcile the association of lectins with RNP complexes and their possible involvement in modulation of HL60 cell proliferation. PMID- 2209719 TI - Intracellular distribution of DNA internalized through calcium phosphate precipitation. AB - Although calcium phosphate precipitation is the most commonly used method for DNA mediated gene transfer, the mechanism for its action is unknown. We showed recently that both transient and stable expression of exogenous genes in the transfected cells are entirely dependent on DNA internalized through active endocytosis. We now report on the subcellular distribution of the endocytosed DNA. After exposure to calcium phosphate-precipitated DNA, cultured fibroblasts internalized less than 10% of the DNA into the nuclei fraction. About 20% was recovered in each of the putative plasma membrane and vesicular organelle fractions. Although over 50% was recovered in the cytosolic fraction, it was completely degraded to oligonucleotides of smaller than 100 bp. In contrast, intact DNA molecules were recovered in all the other subcellular fractions. Similar patterns of DNA distribution were observed not only in the easily transformed mouse cells (Ltk-) but also in the transformation-resistant human primary fibroblasts. In conclusion, DNA-mediated gene transfer by calcium phosphate precipitation is an inefficient procedure because over 50% of the DNA is almost immediately degraded and released into the cytosol. Contrary to accepted views, DNA macromolecules do not seem to pass through the cytosol before reaching the nuclei. A novel transport pathway is proposed in which exogenous DNA molecules may be transferred directly by intermediary vesicles from the endocytic lysosomal compartment to the nucleus. PMID- 2209718 TI - Density-dependent expression of ganglioside GM3 by human skin fibroblasts in an all-or-none fashion, as a possible modulator of cell growth in vitro. AB - The expression of GM3 in human skin fibroblasts (cell type MF II) was investigated biochemically and immunochemically by means of the monoclonal antibody M2590. A cell density-related increase in total gangliosides (about threefold) and especially in GM3 (about sixfold) was found upon attainment of confluency. Immunostaining with mAb M2590 revealed that in preconfluent cultures GM3 is expressed by only a few cells in an all-or-none fashion. The portion of GM3-expressing cells increases in parallel with cell density. In confluent cultures, which are growth-arrested by contact inhibition, all cells are intensely stained by mAb M2590, indicating a high content of GM3 in the plasma membrane. These data suggest that increased cellular M2590 binding is due to an increased GM3 content rather than to an altered conformation or arrangement in the cell membrane. GM3-expressing cells usually show a broad, flat morphology, like that of cells in the resting state (G1/G0-phase) of the cell cycle. The M2590 staining on these cells appear as clusters, orientated along straight lines and indicating an ordered distribution of GM3 in the plasma membrane. A dose dependent inhibition of cell growth by addition of exogenous gangliosides supports the possible involvement of these glycosphingolipids in the regulation of cell growth. PMID- 2209720 TI - Lactate production and amino acid incorporation in interleukin 3-dependent, factor-deprived hemopoietic murine cell lines. AB - Interleukin 3 (IL-3) stimulates the growth of various types of hemopoietic progenitors. In vitro, survival of a series of murine cell lines derived from either neoplastic or nonneoplastic hemopoietic tissue shows a strict IL-3 dependence. In order to test the implication of energy metabolism in this dependence as claimed in several studies, intracellular ATP levels as well as accumulative lactate release were measured in the murine hemopoietic lines FDC P1, 32Dcl.23, DA-1, DA-3, NFS-60, and NFS-78. ATP levels showed little or no changes within 4-6 h of IL-3 starvation. In the absence of IL-3 the accumulative lactate release ranged from 1.4 to 2.6 mM, and in its presence values between 1.5 and 3.4 mM were recorded within 7 h. Only 32Dcl.23 showed an almost complete suppression of lactate release upon IL-3 withdrawal. The cell cycle times of these cell lines determined by flow cytometry ranged between 9 (DA-3) and 24 h (NFS-78). In the presence of IL-3 there was a significant inverse relationship between cell cycle times and lactate production. It is concluded that neither ATP generation nor the metabolic pathway of lactate production, although the latter correlated with proliferative activity in the studied cell lines, is controlled by IL-3. Furthermore, no control by IL-3 of essential amino acid incorporation into proteins was detected in cell lines 32Dcl.23 and NFS-60. PMID- 2209721 TI - Alterations of cell cycle kinetics and vimentin expression in TPA-treated, asynchronous MPC-11 mouse plasmacytoma cells. AB - Vimentin expression throughout the cell cycle has been analyzed at the single cell level in asynchronously growing MPC-11 cells using multiparameter flow cytometry. We have previously shown that these cells normally lack detectable amounts of intermediate filament proteins. In the presence of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), cell proliferation ceases and large quantities of the intermediate filament protein vimentin are synthesized and accumulate in most of the cells. In the present study, the short-term effect of TPA on distribution of cells within the cell cycle was a depletion in early S phase followed by a depletion in mid- and late S phase. In parallel, the G1-phase fraction increased significantly. In addition, a delay in progression through G2/M phase was observed. These data strongly suggest an inhibition of progression of cells through the cell cycle in G1 phase as the primary event on cell cycle kinetics elicited by TPA. Vimentin accumulation could be detected by flow cytometry as early as 2 h after TPA addition; at this time, the percentage of vimentin-positive cells was highest in G2/M phase. Prolonged TPA treatment induced vimentin accumulation in cells of all cell cycle phases. However, even at later times, the G1-phase population consisted of two subpopulations with low and high vimentin content, respectively. The fraction of cells which displayed a higher level of vimentin probably represents those G1-phase cells which previously had undergone cell division in the presence of TPA. Our data indicate that TPA-induced vimentin synthesis is regulated in a cell cycle-dependent manner and is maximally induced in cells which have passed a putative cell cycle restriction point in G1 phase. PMID- 2209722 TI - Induction of nuclear lamins A/C in macrophages in in vitro cultures of rat bone marrow precursor cells and human blood monocytes, and in macrophages elicited in vivo by thioglycollate stimulation. AB - Hemopoietic cells from blood and bone marrow of mammals usually do not express lamins A/C but only lamin B, and this feature distinguishes these cells from the vast majority of somatic cells of the adult animal, which reveal lamins A/C as well as lamin B. Here we have cultivated rat bone marrow precursor cells and human monocytes isolated from peripheral blood in tissue culture supplemented with certain growth factors. These conditions allow bone marrow precursor cells and monocytes to differentiate almost quantitatively into accessory cells and/or mature macrophages. The different cell types in the cultures can be identified both morphologically and by other assays. Antibodies specific for mouse A/C lamins, human A/C lamins, or B lamins have been used to define the lamin complement as a function of time in culture and of cell type. A dramatic increase in lamin A/C-positive cells was observed in the first 3 days of culture with both accessory cells and macrophages expressing lamins A/C as soon as such cell types could be identified. Parallel in vivo experiments showed that treatment with thioglycollate caused the percentage of lamin A/C-positive peritoneal macrophages to increase from 5 to 80% between Days 0 and 6. PMID- 2209724 TI - T98G glioma cells have nicks in DNA in quiescent phase. AB - Human glioblastoma-derived cell line, T98G, is arrested in the G1 phase of the cell cycle when serum is deprived. Using this cell line, we investigated the relation between the cell cycle and DNA single-stranded breaks, "nicks," by an in situ nick-translation method. When T98G cells were cultured without serum for 60 h, many small cells with condensed chromatin and scanty cytoplasm appeared. These small cells that were immunohistochemically considered to be in the G0 or early G1 phase had many nicks in DNA. When serum was added, these small cells with nicks disappeared within 1 to 4 h. VP-16, a DNA topoisomerase II inhibitor, delayed the disappearance of these small cells with nicks. This indicated that the action of DNA topoisomerase II on the chromatin is required to repair nicks in T98G glioma cells and to promote the progression from the quiescent to the proliferating phase. PMID- 2209723 TI - Immunocytochemical identification of the human alpha 2-macroglobulin receptor in monocytes and fibroblasts: monoclonal antibodies define the receptor as a monocyte differentiation antigen. AB - The alpha 2-macroglobulin receptor was recently purified from rat liver and human placenta. Three different monoclonal antibodies have now been raised against the human receptor and expression of the 440-kDa receptor protein is demonstrated in human placenta, fibroblasts, liver, and monocytes by immunoblot analysis. Flow cytometric studies showed that anti-alpha 2-macroglobulin receptor monoclonal antibodies bind to 90-100% of the blood monocyte population and not to other blood cells. This defines the alpha 2-macroglobulin receptor as a monocyte differentiation antigen, different from any of the classified leucocyte cluster determinants. Electron microscopic gold immunocytochemistry revealed the subcellular distribution of the receptor in human cultured monocytes and fibroblasts. In these cells, 18-33% of the gold particles were found on the outside of the plasma membrane, and in fibroblasts, especially, in coated invaginations. The intracellular receptors were mainly distributed in vesicles and tubular structures. PMID- 2209725 TI - Temperature-dependent association of DNA polymerase alpha activity with the nuclear matrix. AB - We have investigated the effect of preincubating isolated nuclei at the physiological temperature of 37 degrees C on the recovery of DNA polymerase alpha and beta activities bound to the nuclear matrix. In HeLa cells, when purified nuclei are incubated for at least 30 min at 37 degrees C prior to extraction with 2 M NaCl and digestion with DNase I, about 30% of nuclear DNA polymerase alpha activity is associated with the final matrix along with about 20% of nuclear protein. If the preincubation is carried out at 0 degrees C, less than 5% of the enzyme activity is resistant to high salt extraction and the protein recovery drops to about 12%. On the contrary, the recovery of nuclear DNA polymerase beta activity bound to the matrix fraction is independent of the temperature at which the preincubation is performed. The same levels of DNA polymerase alpha activity are found to be matrix associated even if reducing and chelating agents are present during the exposure of isolated nuclei to 37 degrees C, suggesting that this phenomenon does not depend on the in vitro formation of disulfide bonds or on some metal ion-protein interaction. Our data could explain why, in the past, different results have been obtained when the association of DNA polymerase alpha with the nuclear matrix has been analyzed. PMID- 2209727 TI - Cell density dependent effect of a tumor promoter on proliferation and chondrogenesis of limb bud mesenchymal cells. AB - When limb bud mesenchymal cells are cultured at high density, chondrogenesis takes place in vitro. Treatment of such cultures with the tumor promoter 12-O tetradecanoyl phorbol 13-acetate (TPA) resulted in complete inhibition of chondrogenesis as indicated from staining the cultures for proteoglycans and from RNA hybridization to cDNA probes specific for four cartilage macromolecules. The effect of TPA varied depending on the initial plating density. At high density, TPA inhibited cell proliferation. At low density, cell proliferation was stimulated by TPA and above a certain cell density, chondrogenesis took place even in the presence of TPA. These results are interpreted to mean that the effect of TPA on chondrogenesis is indirect, possibly through its influence on cell proliferation. PMID- 2209728 TI - Spatial organization of extracellular matrix and fibroblast activity: effects of serum, transforming growth factor beta, and fibronectin. AB - The goal of our research is to understand reciprocal relationships between cell function and tissue organization. We studied the regulation of fibroblast activity in an in vitro culture model that recapitulates in continuous fashion the cycle of events occurring during connective tissue repair. We present evidence that concomitant with spatial reorganization of the extracellular matrix, there was a dramatic decline in extracellular matrix synthesis and cell proliferation. Therefore, spatial reorganization was a crucial turning point for fibroblast activity. Factors that regulated the timing of spatial reorganization included serum, transforming growth factor beta, and fibronectin. By accelerating spatial reorganization of the cultures, transforming growth factor beta led to a relative decrease in cell proliferation and extracellular matrix synthesis. By retarding spatial reorganization of the cultures, fibronectin led to a relative increase in cell proliferation and extracellular matrix synthesis. The results indicate that spatial information in the three-dimensional cell-matrix interaction permits higher order, tissue-level regulation of fibroblast function. PMID- 2209726 TI - Mitogenic effects of transforming growth factor type e on epithelial and fibroblastic cells--comparison with other growth factors. AB - Transforming growth factor type-e (TGFe) is a novel TGF which was first described as a growth factor possibly involved in autocrine stimulation of anchorage independent growth of carcinoma cells. Its later identification in normal tissues, plasma, and platelets suggested a role for TGFe in normal cell growth. This study shows that TGFe stimulates both anchorage-dependent and -independent growth of epithelial and fibroblastic cells of nonneoplastic origin. The mitogenic activity of TGFe in monolayer is slightly less than that of basic fibroblast growth factor, equipotent to that of epidermal growth factor, and greater than that of IGF-1. TGFe acts as a progression factor for both AKR-2B and Balb-3T3 cells. TGFe is also a potent mitogen for normal human epidermal keratinocytes and may therefore play a role in epidermal growth and regeneration. PMID- 2209729 TI - Tubular lysosomes and their drug reactivity in cultured resident macrophages and in cell-free medium. AB - Lysosomes were assessed in normal living resident mouse peritoneal macrophages, using mainly phase-contrast microscopy (PCM), darkfield microscopy (DFM), and fluorescence microscopy (FM) after terminal acridine orange (AO) staining; these procedures avoided dyes during experimentation. After a few hours of culture a variable proportion of the normal spherical lysosomes began to assemble in a linear fashion. Fully formed tubular structures, with appearances generally recognized as characteristic of tubular lysosomes (TL), could be seen by PCM or, after labeling, by FM, at 2-5 days (best usually at 4-5 days). This peak was followed by a reduction, and at 8-10 days most of the TL had disappeared, leaving only spherical lysosomes. Renewal of the medium at this stage was followed by a temporary reappearance of TL, suggesting that the medium was a major factor in their initial development also. Formation of TL was enhanced by chloroquine (Cq), though to a lesser degree than by phorbol ester (PMA); in contrast NH4Cl (like Cq a weakly basic amine) caused their disassembly into spherical lysosomes. Manual disruption of the monolayer macrophages enabled TL to be transferred to a cell free medium, in which they remained apparently stable for several hours. Two known microtubule depolymerizers caused disassembly of TL in the intact cells, reinforcing the idea that the TL are associated with the cytoplasmic microtubule (MT) system; but these agents were inactive in vitro, suggesting that disorganization of the system was responsible for this change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2209730 TI - Outbreaks of infection with methicillin-resistant Staphylococcus aureus on neonatal and burns units of a new hospital. AB - Multiple introductions of methicillin-resistant Staphylococcus aureus (MRSA) strains occurred to a new hospital in Hong Kong. Two years of clinical microbiological surveillance of the resulting outbreaks was combined with laboratory investigation by phage and antibiogram typing, and plasmid profiling. The outbreaks on the special care baby (SCBU) and burns (BU) units were studied in detail, and colonization of staff and contamination of the environment were investigated. MRSA were spread by the hands of staff on the SCBU, where long-term colonization of dermatitis was important, but were probably transmitted on the BU by a combination of the airborne, transient hand-borne and environmental routes. Simple control measures to restrict hand-borne spread on the SCBU were highly effective, but control was not successful on the BU. PMID- 2209731 TI - Characterization of the antibody response in Corynebacterium jeikeium septicaemias. AB - Corynebacterium jeikeium causes septicaemia in neutropenic patients usually after colonizing intravenous lines. This paper reports the results of immunoblotting sera from 14 patients with a C. jeikeium septicaemia. Recovery from the septicaemia was associated with production of both IgM and IgG against antigenic bands of 50, 52 and 110 kDa. Antibody against the 110 kDa band was present in controls but the antibody against the 50 and 52 kDa was specific to those patients who had on-going or previous C. jeikeium infection. A case of C. jeikeium endocarditis is also presented and here recovery was associated with seroconversion to the 50 and 52 kDa bands. PMID- 2209732 TI - Cell surface hydrophobicity, adherence to HeLa cell cultures and haemagglutination pattern of pyelonephritogenic Escherichia coli strains. AB - Cell surface hydrophobicity, haemagglutination pattern and adherence to HeLa cells were examined in 230 strains of Escherichia coli collected from women (n = 61 strains) and children (n = 65 strains) with non-obstructive acute pyelonephritis and in 104 faecal control strains of E. coli from healthy adults (n = 71 strains) and children (n = 33 strains). Pyelonephritogenic E. coli strains showed a significantly increased incidence of hydrophobic properties (90%) and mannose resistant haemagglutination (MRHA) of human erythrocytes (83%) than faecal control strains (64 and 23% respectively, P less than 0.001 in both cases). Mannose sensitive haemagglutination (MSHA) was observed in 48% of the pyelonephritogenic E. coli strains and in 50% of the faecal control strains (NS). The incidence of adherence to HeLa cells was low both in pyelonephritogenic and faecal control strains, 6 and 7% respectively (NS). The bacterial phenotypes MRHA + MSHA + and MRHA + MSHA- appeared significantly more often in pyelonephritogenic E. coli strains (35 and 48% respectively) than in faecal control strains (5 and 17% respectively, P less than 0.001 in both cases). The phenotype MRHA- MSHA + occurred significantly more often in control strains (45%) than in pyelonephritogenic strains (13%, P less than 0.001). Eighty-three per cent of the pyelonephritogenic E. coli strains expressing hydrophobic properties showed MRHA and 50% of the hydrophobic strains showed MSHA. There were no significant correlations between cell surface hydrophobic properties and haemagglutination pattern or adherence to HeLa cells in pyelonephritogenic E. coli strains nor in faecal control strains. PMID- 2209733 TI - The incidence of virulence factors in mesophilic Aeromonas species isolated from farm animals and their environment. AB - Sixty-one isolates of Aeromonas spp. from the faeces of pigs, cows and a variety of associated environmental sources were examined for the characteristics that are reputed to have roles in pathogenicity. Most isolates of Aeromonas hydrophila were cytotoxic (96.4%) and were capable of producing cell elongation factor (75%) and haemagglutinins (67.9%). In contrast few of the Aeromonas caviae isolates produced these three markers (13.6%, 27.3% and 36.4% respectively). In general, Aeromonas sobria occupied an intermediate position (36.4%, 27.3% and 54.5%), but they did produce the highest mean invasion index for HEp-2 cells. Statistical analysis revealed significant associations between the carriage of these factors and it was clear that many isolates of aeromonads from water and animals possessed the full battery of putative virulence factors. PMID- 2209734 TI - The epidemiology of Salmonella infection of calves: the role of dealers. AB - Salmonellas were detected in the environment of 10 of the 12 calf dealers' premises studied. The cleaning and disinfection routines were often ineffective and salmonellas were isolated from 7.6% and 5.3% of the wall and floor samples before disinfection and 6.8% and 7.6% afterwards. Eight different salmonella serotypes were detected, of which the commonest were Salmonella typhimurium, predominantly phage type DT204C, and S. dublin. Plasmid profiles were used to fingerprint S. typhimurium DT204C and the results indicated that with the exception of one of the premises, prolonged salmonella-persistence in the environment was not occurring. Three separate epidemics of salmonellosis in calves were studied by use of plasmid profile analysis. The results illustrated the role of delers, and their subcontractors, in the dissemination of salmonellas. The study concludes with suggestions for methods to reduce the spread of salmonellas in the calf marketing chain. PMID- 2209735 TI - Salmonella colonization in commercial pet turtles (Pseudemys scripta elegans). AB - An epidemiological survey was conducted on two commercial turtle farms in southern Louisiana to determine the reason for an apparent increase in the prevalence of Salmonella spp. in turtle hatchlings at the time of pre-export certification examination. Pond water was consistently found to be contaminated (6/36 samples) with either Salmonella newport, S. arizonae, or S. poona. Environmental specimens obtained from eggs and turtle hatcheries (204 specimens) failed to yield Salmonella spp. A sample comprising 197 hatchlings, derived from a batch previously demonstrated to be contaminated, showed a salmonella prevalence of 12%, with S. arizonae and S. poona the only serotypes isolated. Four serotypes of Salmonella sp. isolated by a certifying laboratory in 1988, and 20 salmonella isolates obtained from hatchling turtles, were all resistant to gentamicin. The emergence of gentamicin resistance in Salmonella spp. isolated from turtles will reduce the effectiveness of preventive measures in use in Louisiana since 1984. PMID- 2209736 TI - Phage type and DNA plasmid profile of Salmonella typhimurium isolates in the area of Isernia, Italy. AB - Thirty-eight Salmonella typhimurium strains isolated from December 1987 to March 1988 in Isernia, Central Italy, were characterized on the basis of their phage type, resistance to antimicrobials and plasmid profiles. According to their phage types, the isolates could be assigned to one of six groups, the prevalent one being PT 195 which accounted for 73.6% of isolates. On the basis of their plasmid content, the isolates could be assigned to one of ten groups. The prevalent plasmid profile (60.0; 6.0; 4.3; 4.0; 3.2 megadaltons) was found in 60.4% of isolates. All the isolates from a particular food (salsicce), and as most of isolates from humans who had consumed this food belonged to phage type 195 and were of the same plasmid profile. The combined use of phage typing and DNA plasmid analysis proved to be a useful tool in identifying epidemiologically related isolates in this investigation. PMID- 2209737 TI - Infection with bacterial enteropathogens in Swedish travellers to South-East Asia -a prospective study. AB - Infection with potential bacterial enteropathogens was studied prospectively in 94 Swedish travellers. Three faecal samples were collected, regardless of diarrhoeal symptoms, after each of three 1-week stays in Singapore, Hong Kong and Japan. The specimens were analyzed for salmonella, shigella, yersinia, campylobacter and different enterotoxin-producing bacteria. A potential enteropathogen was identified in 30% (28/94) of the participants, i.e. in 26% of the healthy and in 39% of the travellers with diarrhoea. The most common isolates were enterotoxigenic bacteria of different species (14%), salmonella (11%) and campylobacter (7%). By performing enterotoxin-tests on six different colonies from the primary culture of each specimen enterotoxigenic Escherichia coli (ETEC) as well as enterotoxin-producing Klebsiella sp., Citrobacter sp. and Morganella morganii were identified. The latter strains were as prevalent as ETEC. In the 33 participants with diarrhoea enterotoxigenic bacteria (18%) and campylobacter (18%) were the most common isolates. Campylobacter-infected travellers developed symptomatic disease (6/7) significantly (P less than 0.02) more often than those infected with salmonella (3/10) or enterotoxigenic bacteria (6/13; 2 ETEC, 4 other species). PMID- 2209738 TI - Sex differentials in susceptibility to lymphatic filariasis and implications for maternal child immunity. AB - This paper reviews epidemiological data to see if there are sex differentials in prevalence, density and clinical pathology due to lymphatic filariasis. Of 53 studies from Africa, South East Asia, the Indian Subcontinent and The Americas, 43 showed a lower mean prevalence of infection in females than in males. Prevalence is consistently lower in women of reproductive age and this is statistically significant in 16 of 32 studies classified by age and sex. Density of infection is also lower in the reproductive age but may be higher in children and in older women. Clinical disease is also lower in women and pathology has a later age of onset and rise to peak prevalence than in males. The paper assesses the evidence that lower rates of infection and clinical pathology are due to less exposure of females to infective vectors. It seems unlikely that exposure alone could account for these differences which are observed for both bancroftian and brugian filariasis, irrespective of periodicity. Several investigators have suggested that females have increased resistance to infection and this is supported by serological studies showing high antibody positivity to adult worm antigens in females. The review concludes that the association with the reproductive years suggests a pregnancy-associated mechanism. This has important implications for maternal-fetal interactions and maternal filarial infection may influence the development of immunity in children. PMID- 2209741 TI - Faecal contamination of water and fingertip-rinses as a method for evaluating the effect of low-cost water supply and sanitation activities on faeco-oral disease transmission. II. A hygiene intervention study in rural north-east Thailand. AB - An intervention study was developed from risk-factors associated with faeco-oral transmission, based on the levels of contamination in stored water and fingertip rinses from households in rural north-east Thailand. This was designed to improve: (a) handwashing, particularly before cooking/eating and after defecation: (b) washing dishes immediately after use. Verbal messages were administered to two intervention groups, one also received a plastic container with a tap to assist these activities. Indicators of compliance were the direct observation of soaking dishes and the presence of faecal streptococci from fingertip-rinses; the main outcome indicator was Escherichia coli contamination of stored water. The intervention group receiving the container was significantly better than the control for indicators of compliance (P less than 0.001 and P less than 0.01) and its stored water was significantly less contaminated (P less than 0.001). There was no significant improvement to the other intervention group, although some features of the intervention had clearly been made available to the control group. Humidity was significantly correlated with fingertip contamination (r = 0.2; P less than 0.001) and with the peak of reported diarrhoea around the beginning of the rainy season. PMID- 2209739 TI - Determination of colonization resistance of the digestive tract by biotyping of Enterobacteriaceae. AB - In studies concerning the effect of antibiotics on faecal microflora, Colonization Resistance is an important parameter. Colonization Resistance correlates inversely with the number of different biotypes of Enterobacteriaceae isolated from faecal samples. Nine healthy volunteers were studied during 6 weeks, in order to determine the natural variation in the number of different biotypes of Enterobacteriaceae per faecal sample. The numbers of biotypes ranged from 1-15 per faecal sample, the mean number of biotypes varied between 2.6 and 7.3 different biotypes per faecal sample per healthy volunteer. Inter-individual variations of five biotypes in the mean number of biotypes per faecal sample are normal. We assessed the minimal number of faecal samples that should be taken for comprehensive biotyping so as to determine reliably the mean number of different biotypes representative for the Colonization Resistance of an individual. It was found that a minimum of four faecal samples was required. PMID- 2209740 TI - Faecal contamination of water and fingertip-rinses as a method for evaluating the effect of low-cost water supply and sanitation activities on faeco-oral disease transmission. I. A case study in rural north-east Thailand. AB - Most villagers in north-east Thailand carry water to their homes and store it in separate containers depending on its subsequent use. In one village, information on water use was collated with the bacteriological quality of stored water, water sources and fingertip-rinses. Stored water quality was a function of water related activities rather than quality at source (P less than 0.0001). Specifically water used for toilet, washing dishes and cooking-related activities was much more contaminated with faecal bacteria than that used for drinking and cooking. Salmonella spp. was significantly more common in water used for washing dishes than drinking (P less than 0.05). Escherichia coli contamination of fingertip-rinses was strongly associated with the individual's activity prior to testing (P less than 0.0001); child care, food and water-related activities produced much higher levels of fingertip contamination than others. Dirty utensils used for cooking and eating were usually left to soak and faecal bacterial growth occurred in this grossly contaminated soak-water. Cross contamination via water handling was the main mechanism of stored water pollution. These results were used to develop a hygiene intervention study presented in a companion paper. PMID- 2209743 TI - Selective antenatal screening for toxoplasmosis and the latex agglutination test. AB - Recent publicity concerning congenital toxoplasmosis has generated a demand for serological assessment of pregnant women. Many laboratories are requested to undertake primary screening in these cases. We assessed the latex agglutination test (LAT) findings in 158 specimens with detectable toxoplasma specific IgM derived from pregnant women. The LAT titres ranged from 16 to greater than or equal to 4000 reflecting the variable antibody response observed in acute toxoplasmosis. We recommend that non-reference laboratories test specimens from pregnant women using the LAT at a screening dilution of 1:16 and select all reactive samples for detailed investigation. PMID- 2209742 TI - Q fever in Plymouth, 1972-88. A review with particular reference to neurological manifestations. AB - Between 1972 and 1988 we have serologically confirmed 103 Coxiella burnetii infections: 46 were acute, 5 were chronic, 52 represented past infections. Details of 61 cases are presented. Of acute cases 80% had respiratory involvement; at least 63% had pneumonias. The incidence (22%) of neurological complications was of particular interest; 40% of these patients had prolonged sequelae. One acutely ill patient died of fulminating hepatitis. Patients with pre-existing pathology or immunosuppression were especially susceptible to C. burnetii. In the absence of acute sera, the complement fixation test alone provided inadequate differentiation between recent and past Q fever: phase II titres persisted at greater than or equal to 80 for more than 1 year after the acute infection in 15 cases; maximum duration of persistence was 14 years. Three patients acquired high phase I titres. Only 5% of cases had chronic Q fever, but in view of the diverse sequelae observed in this series, we suggest that long term serological and clinical follow-up of all cases of Q fever is fully justified. PMID- 2209745 TI - A review of outbreaks of infectious disease in schools in England and Wales 1979 88. AB - In this review of 66 outbreaks of infectious disease in schools in England and Wales between 1979-88, 27 were reported from independent and 39 from maintained schools. Altogether, over 8000 children and nearly 500 adults were affected. Most of the outbreaks investigated were due to gastrointestinal infections which affected about 5000 children: respiratory infections affected a further 2000 children. Fifty-two children and seven adults were admitted to hospital and one child with measles died. Vaccination policies and use of immunoglobulin for control and prevention of outbreaks in schools have been discussed. PMID- 2209746 TI - Isolations of African horse sickness virus from vector insects made during the 1988 epizootic in Spain. AB - This paper describes the first isolations of African horse sickness virus (AHSV) from insects in Spain. Seven isolations of AHSV serotype 4 were made; four from Culicoides imicola a known vector of the virus elsewhere, two from mixed pools of Culicoides species not including C. imicola and one from blood engorged mosquitoes. Three further isolations of AHSV serotype 4 were also made from horses kept adjacent to the insect collecting sites. This work presents the first definitive identification of the vectors of AHSV in Spain during the 1987, 88 and 89 epizootics. Suggestions are also made concerning the significance of these findings with regard to the epidemiology of African horse sickness in Spain. PMID- 2209744 TI - Serological study of the prevalence of toxoplasmosis in asymptomatic patients infected with human immunodeficiency virus. AB - Asymptomatic individuals seropositive for antibody to human immunodeficiency virus (HIV) were investigated for the presence of toxoplasma specific antibody. Serological examination was performed using multiple assays. Of 500 patients studied 133 had serological evidence of previous exposure to Toxoplasma gondii. Specific IgM was detected in 7 patients using ISAGA and 2 patients by DS-ELISA. The immunoglobulin-G annual seroconversion rate was calculated to be 0.75%. The results of this study indicate 27% of HIV positive patients in the UK are at risk of developing life-threatening secondary reactivation of cerebral toxoplasmosis in association with AIDS. A further 0.5-1% per year may suffer primary toxoplasmosis. PMID- 2209747 TI - Metabolic studies of galactosemic cataract. AB - Experimental diabetic and galactosemic animal models are widely used to study diabetes-induced complications. Galactose feeding can rapidly produce cataract, retinopathy and nephropathy; it is therefore favored over the diabetic model. Although the common feature for both models is the activation of aldose reductase, there are substantial differences between the two--not only does the rate of cataract progression differ but the metabolic patterns are far more complex than for polyol production alone. We here present the result of a comparison between diabetic and galactosemic lenses and show the differences in phosphorus and aldose metabolism, cell integrity and osmotic environment. PMID- 2209748 TI - Optical constants and dimensions for the myopic, hyperopic and normal rhesus eye. AB - Complete optical constants and physical dimensions are presented for eight ametropic rhesus eyes in the range from -11.00 diopters of myopia to +8.00 diopters of hyperopia and compared with the same measurements from 40 essentially emmetropic normal control eyes. The optical constants are calculated from a Gullstrand analysis modified for the rhesus eye, and include focal lengths, cardinal points, lens power and total optical power. The physical dimensions, from keratometry and ultrasound, include corneal radius, anterior chamber depth, lens thickness, vitreous depth and axial length. A regression analysis of the data shows that refraction is strongly correlated with both axial length and vitreous depth (at the rate of 3.7 and 4.2 diopters mm-1, respectively; correlation coefficients of -0.962 and -0.821) but is essentially independent of lens power, corneal power, and total optical power. These results allow us to infer that experimentally induced ametropia in the rhesus is caused by a distortion of the globe, and is not caused by the cornea or the lens. PMID- 2209749 TI - Autosomal dominant rod-cone dysplasia in the Rdy cat. 1. Light and electron microscopic findings. AB - Detailed morphological analyses, including retinal layer thickness studies, were performed on heterozygous affected cats with autosomal dominant rod-cone dysplasia (gene symbol Rdy). Abnormalities were evident in retinas from the earliest age examined (2 weeks). Both rod and cone photoreceptors were affected equally by the dystrophy which was characterized by retarded and abnormal development of the visual cells. Photoreceptor inner segments remained rudimentary and outer segments did not elongate normally. Outer segment material was sparse and consisted mostly of whorls of disorganized and disoriented disc lamellae. Photoreceptor cell synaptic terminals showed delayed and incomplete synaptogenesis. Degenerative changes were first observed at 4.5 weeks of age and were characterized by the appearance of pyknotic nuclei in the outer nuclear layer and displacement of photoreceptor cells into the subretinal space. Degeneration began in central retinal regions and proceeded towards the periphery, resulting in progressive loss of the photoreceptor cell layers. By 30 weeks of age only two to five rows of nuclei remained in the outer nuclear layer. Area centralis degenerative lesions in advanced affected eyes were characterized by focal absence of the retinal pigment epithelium and choriocapillaris and thinning of the underlying tapetum. Retinal autoradiography showed that in normal kittens aged between 4.5 and 11 weeks of age rod outer segment renewal rates varied between 2.49 and 2.79 microns per 24 hr. The failure to form a labelled band in retinal autoradiograms from Rdy-affected kittens most probably indicates defective rod disc morphogenesis. It appears that the genetic defect in Rdy cats permits retarded development of the photoreceptor cells, but becomes lethal when these cells begin functional differentiation. PMID- 2209750 TI - Lectin binding patterns in developing canine retina. AB - Developing canine retina, fixed in Bouin's or Tellyesnizky's acetic alcoholic formalin, was examined with a battery of biotinylated lectins. ConA and WGA consistently bound to all retinal layers including the tapetum cellulosum, retinal pigment epithelium, inner and outer segments, plexiform layers and ganglion cells. Binding became more intense with increased age. S-WGA bound to apical portions of the retinal pigment epithelium and to outer segments. Outer segments also bound ConA, WGA and RCA. DBA preferentially labelled all inner segments, while PNA bound to a subpopulation of inner segments. RCA bound intensely to retinal vessels as did PNA after neuraminidase treatment. UEA did not consistently bind to any layers. There was transient binding by some lectins at different developmental stages. This study indicates that canine retina demonstrates differential expression of glycoproteins, as indicated by lectin binding, during development and that this expression is temporally and topographically regulated. PMID- 2209751 TI - Calpain II in two in vivo models of sugar cataract. AB - Cataracts were produced in rat lenses by either feeding a diet containing 50% galactose or by inducing diabetic condition by intravenous injection of streptozotocin. Proteolysis of crystallins, protease activity of calpain II enzyme (EC 3.4.22.17), and presence of calpain molecule (antigen) were determined at four cataract stages--I, cortical vacuoles, II, vacuoles plus hazy cortex, III, nuclear cataract, and IV, mature cataracts. Calpain activity was normal or moderately elevated at early stages of galactose and diabetic cataracts. Later stages III and IV showed proteolysis of lens crystallins, increased proportion of insoluble proteins, loss of calpain enzyme activity and calpain molecule from the soluble fraction, and reduced amounts of calpain associated with insoluble pellet. In galactose cataract, the largest increase in lens calcium were found when proteolysis was present. These results provide evidence for calpain-induced proteolysis of lens crystallins in two in vivo models of sugar cataracts in rodents. PMID- 2209752 TI - Corneal autofluorescence in diabetic and penetrating keratoplasty patients as measured by fluorophotometry. AB - At first it was verified that the major part of the fluorophotometer signal obtained when measuring corneal autofluorescence originated from fluorescence and not from scatter of excitation light at the corneal surface. The minimum percentage of the signal which can be attributed to fluorescence was determined using a fluorescence blocking filter placed in the excitation and fluorescence light path, respectively. The minimum percentages in two healthy controls, two diabetic patients and two patients after penetrating keratoplasty ranged from 75% to 93% (mean 84%). Then the corneal autofluorescence was determined in 22 healthy controls, 18 non-insulin-dependent diabetes mellitus (NIDDM). 23 insulin dependent diabetes mellitus (IDDM) and 21 penetrating keratoplasty patients in order to detect a possible difference in autofluorescence as a result of diabetes or penetrating keratoplasty. The means of the corneal peak autofluorescence values in the NIDDM, IDDM and penetrating keratoplasty patient groups were significantly higher than that in the healthy control group (mean values in ng equivalent fluorescin ml-1: 18.0 +/- 4.2 S.D., 20.6 +/- 5.1 S.D., 17.9 +/- 5.5 S.D. and 13.7 +/- 3.7 S.D., respectively; P less than 0.01). The mean values in the NIDDM and IDDM patients did not differ significantly (P = 0.09). The autofluorescence values were independent of age in all four groups (linear correlation coefficient: r less than 0.47). The corneal peak autofluorescence was linearly correlated with the diabetes duration in the NIDDM and IDDM patients [r = 0.6, P = 0.02; increase: 0.36 ng equiv. fluorescein ml-1 yr diabetes-1]. Our results show that corneal autofluorescence is an easily obtained parameter which can be of assistance in evaluating corneal metabolism. PMID- 2209753 TI - Bovine corneal aldehyde dehydrogenase: the major soluble corneal protein with a possible dual protective role for the eye. AB - Bovine corneal aldehyde dehydrogenase was purified to homogeneity and characterized with aldehyde substrates at pH 7.4. The enzyme was a dimer with a subunit size of 65 kDa. Using kcat/Km values as an indication of substrate efficacy, aldehyde products of lipid peroxidation were recognized as the likely 'natural' substrates. Protein yields from enzyme purification, as well as electrophoretic analyses of crude and purified enzyme preparations, demonstrated that this enzyme is the major soluble protein in bovine cornea, and constitutes around 0.5% wet weight of tissue. A dual role in protecting the eye against UV-B light is proposed--oxidation of aldehydes generated by light induced lipid peroxidation, and the direct absorption of UV-B light by bovine corneal ALDH. PMID- 2209754 TI - The localization and timing of post-translational modifications of rat rhodopsin. AB - Rat retinas were labeled by incubation with, or intravitreal injection of, [14C]leucine along with tritiated palmitic acid, glucosamine or galactose. At selected intervals, subcellular fractions were prepared on linear sucrose gradients and rhodopsin was extracted and purified by affinity chromatography and gel electrophoresis. Time courses revealed that leucine rapidly and transiently labeled the rhodopsin in the rough endoplasmic reticulum (RER), with a maximum at 1.5 hr post-injection. Subsequently, the rod outer segments (ROS) contained the labeled rhodopsin, with the ROS labeling maximally at 6-12 hr. Palmitate labeling followed the same pattern but was subject to a delay, presumably because of a large intracellular pool of the fatty acid. With palmitate the RER rhodopsin was not maximally labeled until 12 hr. The acylation of rhodopsin takes place in the RER sometime after the polypeptide has been translated but before transport to the Golgi. Glucosamine labeling was also delayed because of intracellular pools of the sugar or its metabolic derivatives. But because of secondary glycosylation in the Golgi, the rhodopsin in the ROS also labeled maximally with glucosamine at about 6 hr. Administration of [3H]galactose resulted in the labeling of rhodopsin both in vivo and in vitro, in part possibly because of its conversion to mannose and subsequent insertion into the core oligosaccharide on the RER. However, in the ROS the ratio of tritium, derived from [3H]galactose, to [14C]leucine decreased by a factor of 2 between 6 and 24 hr post-injection. Moreover, between 6 and 12 hr post-injection, labeled rhodopsin molecules in the ROS underwent a shift in mobility on gels indicative of trimming to a lower molecular weight. Thus some sugar residues may be added to the rhodopsin in the inner segment and removed in the ROS. PMID- 2209755 TI - Effects of ultraviolet irradiation on prostaglandin-E2 production by cultured corneal stromal cells. AB - We examined the effects of ultraviolet (UV) irradiation on the release of prostaglandin E2 (PGE2) by rabbit corneal stromal cells in culture. Considerable amounts of PGE2 were present in the media of control corneal cultures following 1, 2, 4, 8 and 24 hr of incubation. Irradiation with UV-A (320-400 nm) for 30 min resulted in more than a 50% increase in PGE2 release. Dexamethasone inhibited PGE2 release by corneal stromal cells. It was, however, ineffective in protecting the cells from the UV-induced release of PGE2. PMID- 2209756 TI - Invertebrate rhodopsin cleavage by an endogenous calcium activated protease. AB - Calcium-activated proteases have been purified from a number of vertebrate tissues, including the retina and lens. These proteases exhibit similar characteristics and are believed to be involved in the regulation of cytoskeletal elements. Here we report the partial purification and characterization of a calcium-activated protease from the squid photoreceptor cell which, when activated, specifically removes 10 kDa from the carboxyl-terminal of squid rhodopsin. No other detectable soluble proteins from the invertebrate photoreceptor are susceptible to cleavage and only one non-opsin, integral membrane protein shows evidence of cleavage. The enzyme requires 5 mM calcium for half maximal activation, and is not significantly activated by other divalent ions. The protease has a molecular weight of approximately 350 kDa, as determined by gel filtration, and when partially purified by casein affinity chromatography, it runs as three main bands of 76, 63 and 36 kDa on SDS-PAGE. The crude protease loses as much as 80% of its activity in 24 hr, whereas the partially purified protease is stable up to 4 weeks at 4 degrees C. PMID- 2209757 TI - Comparison of photoreceptor-specific matrix domains in the cat and monkey retinas. AB - Two lectins, wheat germ agglutinin (WGA) and peanut agglutinin (PNA), were used to compare domains within the interphotoreceptor matrices (IPM) of the cat and monkey, two species where the morphological relationship between the retinal pigment epithelium (RPE) and photoreceptors is distinctly different. In the monkey, PNA labeling was heaviest over the cone outer segments and a discrete region of the interphotoreceptor matrix bordering the cone inner and outer segments--a region which has been termed the cone matrix sheath. Near the apical border of the RPE, the outer margin of the PNA-labeled matrix is surrounded by a circular array of apical microvilli. In the cat retina, PNA labeling was highest over a region of the IPM lying between the outer margin of the cone sheath processes and surrounding rod matrix. In contrast, intracellular labeling of cone inner and outer segments was sparse. The RPE apical processes forming the cone sheath were not labeled. In the monkey retina, WGA preferentially labeled rod outer segments and the region of the IPM around rod inner and outer segments. The cone matrix sheath was not preferentially labeled using this lectin. Rod inner segments and cone inner and outer segments were labeled moderately. In the cat retina, WGA labeling was dense over both rod outer segments and cone outer segments as well as the cone sheath. Rod and cone inner segments, as well as the IPM around both rods and cones, were moderately labeled. These observations suggest that the specialized processes arising from the apical surface of retinal pigment epithelial cells, together with photoreceptor-specific extracellular matrix domains, contribute to the formation of specific microenvironments around rod and cone photoreceptor cells. PMID- 2209758 TI - The dual regulatory role of interleukin 4 is mediated through a direct effect on the target cell. AB - The mechanisms responsible for regulating the growth and differentiation of pluripotent stem cells involve the complex interaction of a series of specific and nonspecific growth factors and signals. In this report, colony-stimulating factor (CSF)-dependent clonal cell lines, recombinant and/or purified CSFs, and clonal assays were used to investigate the mechanism of interleukin 4 (IL-4) induced modulation of CSF-dependent cell growth. IL-4 inhibits in a dose dependent fashion either the interleukin 3 (IL-3)- or granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced growth of the myelomonocytic progenitor cell line, FDC-P1. This inhibitory effect of IL-4- on IL-3- or GM-CSF induced cell growth was verified using normal bone marrow cells. Our data supports the hypothesis that IL-4 is acting directly on the progenitor cell and not indirectly through the action of accessory cells. Further, because the inhibitory effect of IL-4 is selective and does not affect all CSF-dependent cell lines, other factors, including the maturational state or the lineage of the cell may be important in dictating an effect, if any, mediated by IL-4. PMID- 2209759 TI - Bioavailability and the mechanisms of intestinal absorption of iron from ferrous ascorbate and ferric polymaltose in experimental animals. AB - The comparative bioavailability from matching quantities of iron in the form of ferrous ascorbate or ferric polymaltose was defined in rats. Studies were carried out in the intact animals under basal conditions and also when requirements for this metal were either increased or decreased by manipulating stores or erythropoietic activity. No significant difference was found in the total quantity of iron absorbed from either salt or complex under any of these circumstances, suggesting that the mucosal mechanism regulating the overall process was common to both. However, the rate of transfer from the lumen into portal blood was distinctive, reaching a maximum with salt at 30 min compared to 24 h for the complex. To explore the possibility that iron from the two sources was initially handled by different subcellular pathways, the radiolabeled compounds were instilled into loops of bowel that had been isolated between ligatures in vivo. Enterocytes were harvested and fractionated, and incorporation into ferritin and transferrin was determined using RIA. From salt, iron appeared rapidly in duodenal but not ileal ferritin, whereas mucosal transferrin increased under conditions of stimulated absorption, suggesting that this protein may act as a shuttle for the metal. In contrast, iron from polymaltose showed a cumulative incorporation into duodenal ferritin over time that correlated with iron absorption, defined by the appearance of radiolabel in the serum and in the carcass; a similar pattern was demonstrable in ileal mucosal cells. Conversely, binding of iron to transferrin was minimal. No iron polymaltose was found within the mucosal cells. It is suggested that the low rate of iron transfer from this ferric complex may reflect its extracellular breakdown in the lumen of the gastrointestinal tract. PMID- 2209760 TI - Effect of culture conditions on in vitro erythroid colony formation in myelodysplastic syndromes. AB - In vitro colony formation by erythroid progenitors from the bone marrow was studied in 42 patients with a myelodysplastic syndrome using both a standard assay for growing erythroid colonies and an assay designed for growing megakaryocyte colonies. In the standard assay 5 patients had normal numbers of erythroid burst-forming unit (BFU-E) colonies, 8 showed reduced numbers of colonies, and 29 patients had no colony formation. Six patients with markedly reduced numbers of erythroid colonies or no colonies at all in the standard assay showed normal or increased numbers of erythroid colonies in the megakaryocyte assay. In three of these patients the erythroid colony morphology was normal, whereas the other three showed abundant diffuse growth of erythroid subclusters with no normal colonies. In the other patients, the erythroid culture results were similar in both assays. These results indicate that the impairment of erythroid colony growth seen in most patients with a myelodysplastic syndrome is, at least in a number of patients, not due to reduced numbers of erythroid progenitors but to unusual milieu requirements of abnormal progenitors. PMID- 2209761 TI - Is the RPM cell line a useful model for the study of megakaryocyte development? AB - The differentiation of megakaryoblasts into megakaryocytes and their release of blood platelets are complex and poorly understood processes. As an aid to investigate this process several cell lines with megakaryocyte characteristics have been established. One of these cell lines is the rat promegakaryoblast-like (RPM) cell line established by Cicoria and Hempling and used by others to describe maturation processes in megakaryocytes. We have used this cell line to study the synthesis of platelet-specific marker proteins. Severe difficulties led us to perform control experiments to confirm earlier findings. We were unable to confirm several of the previous reports, and we conclude that this particular cell line should not be recommended for the study of megakaryoblast differentiation. PMID- 2209763 TI - Differential toxicity of carbovir and AZT to human bone marrow hematopoietic progenitor cells in vitro. AB - We have studied the in vitro effects of carbovir as compared to 3'-azido-3' deoxythymidine (AZT) on the growth of clonal bone marrow-derived hematopoietic progenitor cells. (-)Carbovir, the enantiomer with anti-human immunodeficiency virus (HIV) activity, exhibited significantly less toxicity to hematopoietic cells than AZT. These in vitro studies suggest that (-)carbovir will exhibit less hematologic toxicity in the therapy of patients infected with HIV either as a single agent or in combination with other agents that inhibit HIV proliferation. PMID- 2209762 TI - Inhibition of human bone marrow and myeloid progenitors by interleukin 2 activated lymphocytes. AB - We have shown that unstimulated and interleukin 2 (IL-2)-activated peripheral blood lymphocytes from both normal donors and cancer patients in remission significantly inhibited the proliferation and granulocyte-macrophage colony formation (granulocyte-macrophage colony-forming cells, GM-CFC) of autologous and allogeneic bone marrow (BM). The inhibition was mediated primarily by CD5+ T cells, although lower levels of inhibition were also displayed by CD56+, CD5- lymphocytes, most of which were CD16-. The CD5+ lymphocytes were also the major effectors responsible for lysis of BM. Inhibition of BM proliferation and GM-CFC colony formation was not dependent on proliferation of the effector cells or cell to-cell contact, because it was also mediated by a soluble factor produced by IL 2-activated lymphocytes. The relevance of these findings to future approaches to leukemia treatment is discussed. PMID- 2209764 TI - Enhancing effect of cyclosporins A and G on bone marrow colony formation. AB - The development of the number of colonies (cell colony-forming units, CFU-C) in soft agar from normal mouse bone marrow (BM) cells was enhanced 60% when total bone marrow cells (BMC) were preincubated for 1 h with either cyclosporin A (CsA) or cyclosporin G (CsG) before plating. Using cell fractionation techniques we found that the removal of macrophages enhanced CFU-C in noncyclosporin-treated BM and that cyclosporins mediated an additional enhancing effect. A similar enhancing effect on CFU-C in noncyclosporin-treated BM was obtained by depleting it of total T cells or Lyt-2.2+ cells. However, CFU-C growth in the residual BM population was no longer enhanced by cyclosporin. Conversely, removal of Lyt-1.2+ cells did not enhance CFU-C in noncyclosporin-treated BM, but the CFU-C in this population were enhanced by cyclosporin treatment. These results suggest that CsA and CsG can increase the cloning efficiency of normal mouse BMC, possibly by inhibiting an endogenous Lyt-2.2+ suppressor cell. PMID- 2209765 TI - A highly sensitive quantitative bioassay for human granulocyte-macrophage colony stimulating factor. AB - Based on the granulocyte-macrophage colony-stimulating factor (GM-CSF) dependency of a newly established human myeloid cell line GM/SO, we developed a highly specific and sensitive bioassay for human GM-CSF. The presence of bioactive GM CSF could be determined by measuring the formazan concentration produced from MTT by the cells that survived and proliferated in the presence of either natural or recombinant human GM-CSF. With this assay we were able to quantify the level of GM-CSF in two human sera as well as in conditioned media from human bladder cell carcinoma cell line 5637, a human fibroblast line, and phytohemagglutinin stimulated peripheral blood mononuclear cells. The sensitivity of the assay allows measurement of concentrations of GM-CSF as low as 0.1 U/ml. PMID- 2209766 TI - Inhibition of human bone marrow progenitors by the synthetic tetrapeptide AcSDKP. AB - The purpose of this work was to study the effects of a tetrapeptide, acetyl-N-Ser Asp-Lys-Pro (AcSDKP), an inhibitor of spleen colony-forming unit (CFU-S) entry into DNA synthesis, on human progenitor cells. Normal human mononuclear cells were incubated with concentrations of the synthetic tetrapeptide ranging from 10( 12) to 10(-7) M for 1.5 and 24 h and then plated in methylcellulose in the presence of human placenta-conditioned medium and recombinant human erythropoietin. The proportion of progenitors in DNA synthesis was determined by the thymidine suicide assay. Incubation with AcSDKP for 24 h leads to a significant inhibition of granulocyte-macrophage colony-forming unit (CFU-GM) and erythroid burst-forming unit (BFU-E) growth and in some cases of erythroid colony forming unit (CFU-E) growth. The inhibition, which was never greater than 50%, was obtained with 10(-10)-10(-9) M AcSDKP, whereas no effect was seen at higher concentrations. The percentage of CFU-GM, BFU-E, and CFU-E in DNA synthesis was significantly reduced in five consecutive patients after incubation of cells for 24 h with inhibitory doses of the peptide, indicating that it is active on cycling cells. Therefore, these studies provide the first evidence that the tetrapeptide AcSDKP, originally obtained from bovine marrow and now chemically synthesized, is able to inhibit the in vitro growth of human progenitors and to decrease their proportion in cell cycle. PMID- 2209767 TI - Differentiation kinetics and globin gene expression by circulating human BFUe in suspension cultures. AB - We studied the kinetics of erythroid differentiation and the globin synthetic patterns of circulating early erythroid progenitors (erythroid burst-forming units, BFUe) stimulated to differentiate in suspension cultures in the presence of interleukin 3 (IL-3) and erythropoietin. Erythroid progenitor cells present at the onset of culture and on successive days (2-12) thereafter were quantitatively assessed by clonal assays, whereas globin synthesis was measured sequentially in aliquots from the suspension culture. Although BFUe numbers increased to a peak value by day 4, the number of progenitors generating larger bursts was progressively decreasing with a concomitant increase in the number of smaller sized bursts. Erythroid colony-forming units (CFUe) and erythroid clusters were first detected by day 4 and peaked on day 6. Proerythroblasts were morphologically identifiable on day 4, and they progressively increased in number and maturity so that, at culture days 10 and 12, 51% and 59% of the culture cells were erythroblasts, respectively. In keeping with the morphologic changes during the liquid culture, globin mRNA was first detected on day 4. gamma/gamma + beta mRNA ratios were highest on days 4 and 6 and declined thereafter. Our results show that circulating BFUe (at least the majority of them) can differentiate and mature as a cohort in suspension cultures, providing terminal progeny with accelerated kinetics compared to semisolid, clonal cultures. In this system the same cohort of cells can be easily sampled throughout the culture for molecular studies on erythroid differentiation. PMID- 2209768 TI - Transfusion of autologous cytotoxic cells leads to failure of unrelated, DLA nonidentical marrow grafts. AB - Dogs conditioned with 9.2 Gy total body irradiation (TBI) and given histoincompatible marrow transplants have a high rate of graft failure. Engraftment can be achieved by using 18 Gy fractionated TBI as preparative regimen. In this study, we tested the effects of infusing, at the time of histoincompatible marrow transplantation, autologous cells that had been stored before beginning high-dose (18 Gy) TBI. Our aim was to identify the peripheral blood mononuclear cells (PBMC) that contribute to failure of marrow grafts. Marrow graft failure was observed in three of three dogs receiving a mean of 2.1 x 10(8) unfractionated autologous PBMC/kg body weight as well as in two of two dogs receiving a mean dose of 0.075 x 10(8) PBMC/kg. When the dose of PBMC was decreased to 0.01 x 10(8)/kg, engraftment was seen in two of two dogs. These experiments thus established a cell dose response for causing marrow graft failure; further studies evaluated which subset of cells mediated this effect. Infusion of 0.09 x 10(8) nylon wool-nonadherent, plastic-nonadherent PBMC/kg was effective in causing marrow graft failure in three of three dogs. In contrast, infusion of 0.03 x 10(8) autologous monocytes/kg, enriched threefold above the number contained in the lower dose of PBMC causing graft failure, was associated with engraftment in four of six dogs. Infusion of 0.13 x 10(8) PBMC/kg treated with L-leucyl-L-leucine methyl ester (Leu-Leu-OMe), a drug that depletes canine cytotoxic T-lymphocytes (CTL), natural killer (NK) cells, and monocytes, permitted engraftment in three of four dogs. These data suggest that cytotoxic lymphocytes mediate failure of histoincompatible marrow grafts. PMID- 2209770 TI - Unlike systemic administration of p-chloroamphetamine, direct intracerebral injection does not produce degeneration of 5-HT axons. AB - Systemic administration of the amphetamine derivative p-chloroamphetamine (PCA) causes degeneration of 5-HT axon terminals in rat brain. The present study was designed to determine whether PCA induces neurotoxic effects by a direct action on 5-HT axon terminals. PCA was administered by microinjection directly into the cerebral cortex of rats. Continuous intracerebral infusions were made over extended time periods (10 min-48 h) to explore whether the induction of neurotoxicity requires a prolonged exposure of axon terminals to the drug. Two weeks after drug administration, brain sections that passed through the injection site were processed for 5-HT immunohistochemistry. The 5-HT innervation of cerebral cortex in PCA-injected animals was compared with that after intracortical injection of saline or of 5,7-dihydroxytryptamine. The results demonstrate that, in the concentrations used, direct application of PCA into the neocortex does not elicit axonal degeneration, even after a continuous infusion for 2 days. This finding suggests that PCA itself is not directly toxic to 5-HT axons. PMID- 2209769 TI - Detection of the hybrid BCR/ABL messenger RNA in single CFU-GM colonies using the polymerase chain reaction. AB - In order to study which hemopoietic precursor cells express the hybrid BCR/ABL fusion mRNA we have developed a technique based on the polymerase chain reaction (PCR) for the examination of single hemopoietic colonies grown on semi-solid agar. The technique was developed by examining single CFU-GM colonies grown from newly diagnosed patients with chronic myeloid leukaemia (CML). RNA was isolated from individual 14 day colonies and reverse transcribed to a complementary DNA (cDNA) copy which formed the substrate for a PCR. We have studied 3 cases of CML using this method and have found that 5 out of 5, 9 out of 10 and 20 out of 23 colonies examined were positive. Thus we describe a simple and useful technique for the study of gene expression in a limited number of hemopoietic precursor cells. PMID- 2209771 TI - Ultrastructural evidence for serotonin-immunoreactive terminals contacting phrenic motoneurons in the cat. AB - The innervation of the phrenic motor nucleus in the cat by serotonin-containing neurons has been studied using retrograde tracing combined with immunohistochemistry at the electron microscope level. It was found that phrenic motoneuron cell bodies and dendrites are contacted by serotonin-immunoreactive synaptic terminals. This finding suggests that the activity of phrenic motoneurons is directly affected by serotonergic neurons. PMID- 2209772 TI - Nimodipine enhances new learning after hippocampal damage. AB - Rats were trained to lever press and then were given either bilateral lesions of the hippocampus or control operations. Half of the rats in each group received oral nimodipine, a calcium entry blocker, while the remaining rats received vehicle, over a 14-day period that began the evening of surgery. The rats were studied on a DRL 20-s schedule of reinforcement (differential reinforcement of low rates of responding) that required them to withhold a response for at least 20 s after their last lever press in order to earn a reward. Rats with lesions that did not receive the drug performed poorly on the DRL 20-s schedule. In contrast, rats sustaining the same hippocampal lesions but given the drug showed scores that were virtually equivalent to those of the sham-operated control animals. Similar trends were observed when the rats were then tested on a DRL 40 s schedule of reinforcement. These findings suggest that nimodipine may attenuate the effects of acute, focal brain lesions on new learning of even difficult behavioral and cognitive tasks. PMID- 2209773 TI - End structure and neuropeptide immunoreactivity of axons in sciatic neuromas following nerve section in neonatal rats. AB - The formation of neuromas after neonatal nerve injury was studied in rats. In neonatal pups, the sciatic nerve was cut and tightly ligated, and a portion of the distal stump was removed. After 6-10 weeks, a nerve-end neuroma had formed in about 70% of the animals. In the remaining animals the nerve had grown on the side of the ligature. The end structure of the neuroma axons was studied using anterogradely transported WGA-HRP injected into the L5 dorsal root ganglion. HRP labeling occurred in the entire proximal sciatic nerve. In the neuroma, labeled fibers branched profusely and either terminated with minor end swellings or turned in the retrograde direction. Immunohistochemistry showed that the fibers which projected into the neuroma presented a moderate immunoreactivity to substance P and neuropeptide Y and a strong reactivity to calcitonin gene-related peptide. The results show that many sensory and sympathetic sciatic nerve fibers survive chronic axotomy in the newborn and contribute to the formation of nerve end neuromas. There are, however, important structural differences between adult and neonatally induced neuromas. PMID- 2209774 TI - Slow intrinsic spikes recorded in vivo in rat CA1-CA3 hippocampal pyramidal neurons. AB - The membrane potential of 45 CA1-CA3 hippocampal pyramidal cells was recorded in curarized and urethanized rats. Two slow spike types were observed together with the usual Na+ type action potential. Slow spikes were termed HTS and LTS because they were essentially identical to the high and low threshold Ca2+ spikes observed in vitro and probably represent the same kinds of activities. LTS and HTS (22 and 29 cells, respectively) were triggered at potentials greater than or equal to 65 mV and less than or equal to 55 mV, had mean durations of 23.7 and 90.4 ms and mean amplitudes of 11.5 and 39.3 mV, respectively, and fired an overriding burst of the action potentials. LTS and HTS were sometimes present in the same neuron (n = 16). Depolarizing pulses triggered rhythmic HTS at rates that increased with depolarization up to a 5 impulses/s maximum. The same limit was found with imposed membrane potential sine currents at frequencies within the theta rhythm range. With spontaneous or imposed hyperpolarizations LTS were evoked by depolarizing, at the break of hyperpolarizing pulses, or spontaneously. They were also evoked at the depolarizing, or recovery, slopes of inhibitory postsynaptic potentials. HTS and LTS supply pyramidal neurons with different firing patterns which enhance the system's integrative possibilities. Evidence is provided that theta is not exclusively generated by network properties, since rhythmic HTS may participate. PMID- 2209775 TI - Systemic injection of kainic acid: gliosis in olfactory and limbic brain regions quantified with [3H]PK 11195 binding autoradiography. AB - Neurodegenerative diseases may result from excessive stimulation of excitatory amino acid receptors by endogenous ligands. Because neuronal degeneration is associated with glial proliferation and hypertrophy, the degenerative changes throughout rat brain following the systemic administration of kainic acid (12 mg/kg) were mapped with quantitative autoradiography of [3H]PK 11195. This radioligand binds to a mitochondrial benzodiazepine binding site (MBBS) on microglia and astrocytes. Analysis of eight horizontal and four coronal brain levels revealed up to 16-fold increases in [3H]PK 11195 binding from 1 to 5 weeks but not 1 day after kainate injection. Increases in [3H]PK 11195 binding were predominantly in ventral limbic brain regions and olfactory projections to neocortical areas, with the olfactory cortex greater than subiculum/CA1 greater than anterior olfactory nucleus, medial thalamic nucleus, and piriform cortex greater than cingulate cortex and rostral hippocampus greater than dentate gyrus, septum, and amygdala greater than entorhinal cortex and temporal cortex. Little or no enhancement of [3H]PK 11195 binding was observed in numerous regions including the caudate-putamen, substantia nigra, nucleus accumbens, olfactory tubercle, cerebellum, thalamic nuclei, choroid plexus, medulla, parietal or occipital cortex, or pons. A 2-fold greater extent of neurodegeneration was obtained in ventral portions of the olfactory bulb, entorhinal cortex, temporal cortex, and dentate gyrus compared with the dorsal portions of these structures. The pattern of increase in [3H]PK 11195 binding closely matched the patterns of neuronal degeneration reported following parenteral kainate injection. These findings strengthen the notion that quantitative autoradiography of [3H]PK 11195 is a valuable tool to quantify the extent of neuronal degeneration. Furthermore, the quantitative changes in [3H]PK 11195 binding in different limbic structures parallel their relative variation in neuropathology observed in Alzheimer's disease but not Huntington's chorea. These findings are in agreement with the idea that excessive stimulation of excitatory amino receptors may contribute to the etiology of Alzheimer's disease. PMID- 2209776 TI - Normal expression of myosin fast alkali light chain 3 in the hindlimb muscle of chick embryos paralyzed with curare. AB - We have used a monoclonal antibody (Mab) raised against the fast alkali light chains of quail pectoral muscle myosin to study the expression of MLC1f and MLC3f in the hindlimb muscle of a staged series of control chick embryos and 16-day embryos that had been paralyzed with curare. The Mab (QBM-2) is highly specific for the fast myosin alkali light chains of chick, hamster, and human muscle myosin. On Western blots, MLC1f is detected in hindlimb actomyosin at all of the stages examined, whereas MLC3f cannot be detected until Embryonic Day 14 (E14). Most of the E16 embryos that had been paralyzed with curare since E4 express detectable levels of both MLC1f and MLC3f in their hindlimb muscles, even though embryos incubated under these conditions do not exhibit spontaneous limb movements. Contrary to other reports, our results demonstrate that muscle contraction is not required for the accumulation of MLC3f. In light of our previous finding that innervation is essential for MLC3f accumulation in limb buds grafted onto the chorioallantoic membrane of chick hosts, these results suggest that some neural influence other than contraction, possibly a trophic factor, may play a role in the developmentally regulated expression of MLC3f in avian limb muscle. PMID- 2209777 TI - Partial denervation of amphibian skeletal muscle does not induce neuronal growth at the node of Ranvier. AB - Following partial denervation of a striated muscle sprouting occurs at the nodes of Ranvier and terminal arborizations of the intact motor neurons. We studied the sprouting response of intact frog (Rana pipiens) motor neurons to partial denervation of the cutaneous pectoris muscle (CP). In the 5-19 days following partial denervation of the CP muscle, tetranitroblue tetrazolium-stained motor neurons exhibited sprouting. However, the mixed response of both nodal and terminal sprouting characteristic to mammalian muscle was replaced by a preferential response of only terminal sprouting. Histological examination showed that in many cases these terminal sprouts appeared to reinnervate abandoned junctional sites on adjacent denervated fibers. Given that nodal sprouting failed to occur for the duration of the experiment, these preliminary results suggest that the cues responsible for nodal sprout formation in the amphibian may differ from those in the mammal. PMID- 2209778 TI - Cytochemistry of 5'-nucleotidase in the superior cervical ganglion of the rat: effects of pre- and postganglionic axotomy. AB - 5'-Nucleotidase, a prominent nucleoside-producing ectoenzyme of glial plasma membranes, was studied by enzyme cytochemistry in the superior cervical ganglion of the rat under normal conditions and after pre- and postganglionic axotomy. In normal ganglia 5'-nucleotidase was restricted to capillary endothelial cells, localized both on the luminal surface and in pinocytotic vesicles. Following preganglionic axotomy, the number of enzyme-positive endothelial vesicles increased, whereas no 5'-nucleotidase was found on reactive Schwann cells during phagocytosis of degenerating preganglionic axon terminals. After postganglionic axotomy an even stronger increase in enzyme-containing endothelial vesicles occurred. In addition, 5'-nucleotidase activity became detectable on the plasma membrane of Schwann cells and proliferating satellite cells, which participate in the detachment of synapses from axotomized neurons. Fibroblasts in the endoneuronal connective tissue of regenerating ganglia also exhibited 5' nucleotidase on their surface. The results obtained suggest that 5'-nucleotidase may be related to specific metabolic requirements of Schwann and satellite cells during regeneration and that these requirements differ from those of reactive Schwann cells after denervation of the ganglion. Postoperative changes in 5' nucleotidase activity on endothelial cells and fibroblasts of the ganglion indicate an involvement of these cells in metabolic response elicited by pre- or postganglionic axotomy. PMID- 2209779 TI - Human beta nerve growth factor obtained from a baculovirus expression system has potent in vitro and in vivo neurotrophic activity. AB - A baculovirus expression vector, which contains the coding sequences for human prepro (beta) nerve growth factor under control of the viral polyhedrin promoter, was constructed. Upon infection of insect cells with the recombinant virus, mature human beta nerve growth factor (rhNGF) was released into the culture fluid. The mature rhNGF was biologically active since rat pheochromocytoma (PC12) and human neuroblastoma (SH-SY5Y) cells were induced to extend neurites upon treatment with this material. This activity was abolished by treating with antiserum prepared against mature mouse beta NGF (mNGF). When compared with mNGF, rhNGF more rapidly elicited the differentiation response in both PC12 and SH-SY5Y cells. In an in vivo assay of cholinergic cell survival, rhNGF was nearly as potent as mNGF in protecting cholinergic neurons from degeneration following a fimbria-fornix lesion. These results show that the baculovirus expression system provides quantities of biologically potent human beta NGF suitable for a comprehensive program of research to ascertain beta NGF's potential as a therapeutic agent for the treatment of Alzheimer's disease. PMID- 2209780 TI - NGF released from a polymer matrix prevents loss of ChAT expression in basal forebrain neurons following a fimbria-fornix lesion. AB - Following a unilateral fimbria-fornix lesion, the delivery of nerve growth factor (NGF) to the ipsilateral lateral ventricle of the rat can prevent the lesion induced loss of choline acetyltransferase (ChAT) expression in the ipsilateral medial septum and vertical diagonal band region. In the present study, the ability of polymer rods to deliver NGF and to prevent a decrease in basal forebrain ChAT expression following a fimbria-fornix lesion was assessed. NGF was loaded into an ethylene vinyl acetate copolymer (EVAc) rod, fabricated by a melt extrusion process. NGF release was established by the ability of the rods to induce neurite extension from PC12 cells and chick E12 dorsal root ganglia. Unilateral aspirative lesions of the fimbria-fornix were performed in adult rats, followed by implantation of a polymer rod into the ipsilateral lateral ventricle. Five animals received EVAc rods containing only the carrier molecule bovine serum albumin (BSA), and six received EVAc rods containing both BSA and NGF. After 2 weeks, ChAT-positive cells were counted in the medial septum and vertical diagonal band regions. Rats with NGF-releasing rods displayed ChAT(+) cell counts ipsilateral to the lesion equal to 88% of those on the contralateral side. In contrast, ChAT(+) cell numbers were 42% in animals with rods releasing BSA only (P less than 0.001). No undue reaction to implanted rods was noted. Following a fimbria-fornix lesion, NGF released from polymer matrices effectively prevents a lesion-induced reduction in ChAT expression in basal forebrain neurons. PMID- 2209781 TI - Sciatic nerve regeneration across gaps within silicone chambers: long-term effects of NGF and consideration of axonal branching. AB - We examined whether the short-term beneficial effects of nerve growth factor (NGF) upon regeneration are sustained over a prolonged period of time across 8-mm gaps within silicone chambers. Rat sciatic nerve regeneration both with and without NGF was examined after 10 weeks. Myelinated counts from the regenerated sciatic and distal tributary nerves were correlated to the numbers of motor and sensory neurons retrogradely labeled with horseradish peroxidase (HRP) applied distal to the regenerated segment. Regenerated sciatic and sural nerves were examined ultrastructurally for morphological analysis. Both regenerated groups by 10 weeks achieved essentially complete counts of myelinated axons in the distal tributary nerves and the regenerated segment of the sciatic nerve compared to the uninjured controls. There were similar numbers of retrogradely labeled sensory and motor neurons in the dorsal root ganglia (DRG) and lumbar spinal cord of both groups and, surprisingly, of the uninjured normal control group. Ultrastructural analysis demonstrated no difference in the distribution of axonal diameters or myelin thickness between the regenerated groups. In evaluating regeneration in experimental silicone chamber models, it is important to determine such parameters as the percentage of neurons that grow across the gap and the incidence of axonal sprouting. One can then make accurate assessments of experimental perturbations and predict whether they improve the naturally occurring regeneration through chambers. These results must ultimately be compared with equivalent determinations in the uninjured nerve. At 10 weeks there was essentially complete regeneration of both the NGF and control regenerative groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2209782 TI - Cell adhesion molecules (CAMs) in adrenal medulla in situ and in vitro: enhancement of chromaffin cell L1/Ng-CAM expression by NGF. AB - We have studied the expression of the cell adhesion molecules (CAMs) L1/Ng-CAM, N CAM, J1/tenascin, and myelin-associated glycoprotein and their common carbohydrate L2/HNK-1 epitope in normal rat adrenal gland sections as well as in adrenal medulla cell culture with and without NGF stimulation. In situ L1/Ng-CAM was observed on the surface of some but not all chromaffin cell clusters, including their closely associated extracellular matrix (ECM). N-CAM immunoreactivity was present on all chromaffin cells and ECM. The ECM of whole medullas also expressed J1/tenascin molecules. In long-term cultures, nerve growth factor (NGF) stimulation enhanced L1/Ng-CAM, N-CAM, and Thy 1.1 immunolabeling on chromaffin cells and their processes. Process outgrowth was greater from chromaffin cell clusters containing S-100 positive Schwann cells as compared to dispersed single chromaffin cells. When long bundles of chromaffin cell fibers were present, S-100, L1/Ng-CAM, and N-CAM positive Schwann cells were always found and were grouped in distinct clusters in the intervals between the chromaffin cells. In some areas, however, after NGF stimulation some chromaffin cell process development occurred despite an apparent lack of close contact with Schwann cells. NGF-activated chromaffin cells also demonstrated neurofilament- and vimentin-like-immunoreactive filaments within cell bodies and their processes. Chromaffin cells were usually found on a layer of N-CAM and fibronectin positive fibroblasts, and often were associated with laminin immunoreactive material. These data suggest a possible role of N-CAM and L1/Ng CAM as well as ECM laminin in process outgrowth from chromaffin cells. PMID- 2209783 TI - Cell adhesion molecules in adrenal medulla grafts: enhancement of chromaffin cell L1/Ng-CAM expression and reorganization of extracellular matrix following transplantation. AB - Intracerebral adrenal medulla grafts have been used in human patients as an experimental treatment for Parkinson's disease, based on studies in animal models of this disorder. However, alterations in chromaffin cell properties after transplantation and the factors controlling graft survival are poorly understood. Since cell adhesion molecules (CAMs) are involved in regeneration and development of neural tissue in vivo and in vitro, the present study was undertaken to determine the expression of CAMs in adrenal medulla isografts. Fragments of rat adrenal medulla were implanted into the right lateral ventricle. The majority of grafts survived quite well, for up to 2 months (the longest studied period). The implanted chromaffin cells did not develop extensive processes. The cells retained tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) immunoreactivity, while phenylethanolamine N-methyltransferase (PNMT) expression was decreased. Surviving transplanted chromaffin cells showed enhancement and spreading of surface L1/Ng-CAM expression as compared to normal chromaffin cells in adrenal medulla. The implanted chromaffin cells demonstrated only partial conversion to neuronal phenotypes. These chromaffin cells did not develop extensive processes, but showed an enhancement of L1/Ng-CAM expression. Surviving chromaffin cells were accompanied by reorganization of their closely associated extracellular matrix (ECM). As compared to normal in situ adrenal medulla, graft ECM demonstrated a substantial increase of L1/Ng-CAM and laminin immunoreactivities and a distinct decrease in J1/tenascin expression. Some adrenal medulla grafts degenerated, particularly when misplaced within the host brain parenchyma. In these cases the grafts showed fragmentation of ECM and gradual disappearance of CAMs. These results suggest that surviving adrenal medulla grafts exhibit increased synthesis of certain CAMs by chromaffin cells, which may be involved in interactions between chromaffin cells and the surrounding ECM. It is speculated that both surviving and degenerating adrenal medulla grafts could provide CAMs and ECM components including laminin to host brain and this way contribute to functional effects of grafts. PMID- 2209784 TI - Regulation of ischemic hippocampal damage in the gerbil: adrenalectomy alters the rate of CA1 cell disappearance. AB - Adrenalectomy protects hippocampal pyramidal cells from transient ischemia in rats. We hypothesized that this effect of adrenalectomy could be generalized to the gerbil. We determined the effect of glucocorticoid manipulation on hippocampal CA1 cell death following transient forebrain ischemia in the gerbil. Adrenalectomy diminished hippocampal damage when performed immediately following transient forebrain ischemia, as in the rat, while glucocorticoid administration resulted in an increase in CA1 pyramidal cell damage. Furthermore adrenalectomy 24 h after the ischemic injury diminished hippocampal damage to roughly the same extent as immediate adrenalectomy. However, if gerbils were examined at longer survival periods after ischemia, the difference in hippocampal damage between adrenalectomized and sham-adrenalectomized was lost. These findings suggest that glucocorticoids influence the rate of hippocampal pyramidal cell disappearance following ischemia. Manipulation of glucocorticoids could be an important adjunct to therapy for preventing ischemic brain damage. PMID- 2209785 TI - Brugia malayi and Brugia pahangi: transmission blocking activity of ivermectin and brugian filarial infections in Aedes aegypti. AB - Brugia malayi- or Brugia pahangi-infected, microfilaremic jirds (Meriones unguiculatus) were treated with ivermectin at a single dose of 200 micrograms/kg body weight, administered subcutaneously. After different time intervals, Aedes aegypti mosquitoes were fed on treated or untreated jirds. Sausage stage, L2, and L3 larvae failed to develop in mosquitoes that fed on jirds from 15 to 30 days post-treatment. After 1 month, the numbers of L3 larvae recovered from mosquitoes fed on treated B. pahangi jirds were comparable to controls. However, the number of L3's recovered from mosquitoes fed on B. malayi jirds remained significantly lower than controls, 2 and 3 months after treatment. This reduction suggests that ivermectin may be more effective in blocking transmission of B. malayi than B. pahangi. Ivermectin treatment had no effect on the mean number of circulating microfilariae in treated jirds. Therefore, mosquitoes ingested comparable numbers of microfilariae when compared to those mosquitoes fed on untreated controls. Only in the case of jirds infected with B. malayi did the circulating microfilarial counts fall 30 days after treatment. The failure of microfilariae to develop to the L3 stage in mosquitoes fed on jirds within 30 days of treatment was not due to failure of mosquitoes to ingest microfilariae. Brugia malayi microfilariae also failed to develop to L3 in mosquitoes that were allowed to feed on microfilaremic jird blood treated with ivermectin (50 ng/ml) in vitro, indicating its efficacy at low concentrations. In addition to N-acetyl glucosamine, microfilariae obtained for a period of 15 days from ivermectin treated but not control jirds showed D-mannose, N-acetyl galactosamine, and L fucose moieties on the surface of the sheath.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2209786 TI - Eimeria vermiformis: differences in the course of primary infection can be correlated with lymphocyte responsiveness in the BALB/c and C57BL/6 mouse, Mus musculus. AB - BALB/c and C57BL/6 mice are high- and low-responders, respectively, to infection with Eimeria vermiformis, this genetically determined difference being immunologically mediated. In order to identify the level at which response phenotype is determined, the proliferation of mesenteric lymph node cells and their ability to transfer immunity adoptively were investigated in each strain; the development of circulating serum antibodies to E. vermiformis was also determined. In all respects BALB/c mice responded earlier than the C57BL/6 but peak values were similar in both strains. The relationship between the temporal differences noted and the characteristic, differing course of the primary infection in the two strains is discussed. PMID- 2209788 TI - Plasmodium cynomolgi: serum-mediated blocking and enhancement of infectivity to mosquitoes during infections in the natural host, Macaca sinica. AB - The infectivity of Plasmodium cynomolgi in its natural host, the toque monkey, Macaca sinica, to Anopheles tessellatus mosquitoes was studied in relation to the evolution of anti-sexual-stage immunity in the host during the course of a blood induced infection. The effects of serum on the infectivity of gametocytes and the intrinsic infectivity of gametocytes to mosquitoes on each day were assessed in membrane feeding experiments. Mosquitoes were also directly fed on the animal on each day. Our results demonstrate that during the very early patent period, before the peak of gametocytemia, the infection serum enhanced the infectivity of gametocytes up to two to three times above their infectivity in normal monkey serum. Subsequently, serum drawn post-peak of parasitemia ceased to enhance, and began to suppress, infectivity. After 2-3 months, long after parasitemias ceased patency, the serum no longer suppressed and between 3 and 4 months the serum again tended to enhance gamete infectivity before losing any significant effect. Serum infectivity enhancing effects were consistent with low indirect immunofluorescence test antibody titers against blood stage parasites first during the very early days of a blood infection before reaching blocking levels, and again during convalescence when antibodies were declining. The serum infectivity blocking effects on gametocytes were seen at the peak of antibody titers from about Days 9 to 23 of an infection. From 78 to 95% of the total infectivity of the parasite to mosquitoes during an infection occurred when infectivity enhancing activity was present in the serum. Hence, the infectivity of the parasite to mosquitoes was largely dependent on infectivity enhancing antibodies in host serum. PMID- 2209787 TI - Leishmania major: expression and gene structure of the glycoprotein 63 molecule in virulent and avirulent clones and strains. AB - Two Leishmania membrane glycoconjugates, gp63 and lipophosphoglycan, have been implicated in parasite attachment and uptake into the host macrophage. Moreover, recent data suggest that parasite virulence is associated with high expression of gp63. In this study we have surveyed gp63 gene copy number, in addition to the level of expression of gp63 mRNA and protein in several Leishmania major isolates, as well as virulent and avirulent strains and clones. The highest level of gp63 expression was found in the avirulent cloned line LRC-L119.3G7, which expresses about a 15-fold higher level of gp63 RNA and protein than the virulent cloned line LRC-L137/7/V121, suggesting that large amounts of gp63 are not sufficient for infectivity and do not correlate with virulence. L119.3G7 has eight copies of the gp63 gene compared to five copies in the virulent cloned line V121 and its parental virulent isolate LRC-L137. A series of avirulent clones derived from LRC-L137 also had five copies of the gene, suggesting that gp63 copy number is maintained among closely related parasites. Different virulent isolates of L. major from different geographic regions exhibited six copies of the gp63 gene. The variation in total gene copy number is due to different numbers of the tandemly repeated gp63 isogene in different strains. Our data show that there is wide variability between strains of L. major in the copy number of gp63 genes as well as in the amount of RNA and protein expressed. PMID- 2209789 TI - Plasmodium falciparum: differential parasite reactivity of rabbit antibodies to repeated sequences in the antigen Pf155/RESA. AB - For selection of immunogens capable of inducing high levels of antibodies reactive with the Plasmodium falciparum antigen Pf155/RESA, rabbits were immunized with synthetic peptides corresponding to sequences based on the repeat subunits EENVEHDA and (EENV)2 from the C-terminus of this antigen. The antibodies obtained were analyzed with regard to binding to synthetic peptides in ELISA and to reactivity with parasite antigens by immunofluorescence or immunoblotting. All antisera reacted with both the peptides EENVEHDA and (EENV)2 as well as with Pf155/RESA. Antibody fractions specific for each of the two peptides were prepared by affinity chromatography on insolubilized peptides. Strong reactivity with antigens in the membrane of erythrocytes infected with early stages of the parasite as well as reactivity with Pf155/RESA in immunoblotting correlated with reactivity of antibody with (EENV)2. Antibody preparations reactive with EENVEHDA and depleted of (EENV)2 reactivity showed only a weak reactivity with Pf155/RESA but reacted also with P. falciparum polypeptides of 250, 210, and 88 kDa. In immunofluorescence, these antibodies stained mainly the intraerythrocytic parasite. Both EENVEHDA- and (EENV)2-specific antibodies inhibited merozoite reinvasion in P. falciparum in vitro cultures, the latter antibodies being the most efficient. This study defines the specificity and cross-reactivity with other P. falciparum antigens of antibodies to the C-terminal repeats of Pf155/RESA. PMID- 2209790 TI - Pf155/RESA antigen is localized in dense granules of Plasmodium falciparum merozoites. AB - Immunoelectron microscopy demonstrated the presence of Pf155/RESA in dense granules of Plasmodium falciparum merozoites rather than in micronemes as previously suggested. Since the dense granules are released after the merozoite enters the parasitophorous vacuole, the role of Pf155/RESA in invasion and subsequent steps of parasite development may differ from that of a molecule located in the micronemes. PMID- 2209791 TI - Leishmania major and L. donovani: a method for rapid purification of amastigotes. PMID- 2209792 TI - Plasmodium falciparum: a rapid assay for cytoadherence of [3H]hypoxanthine labeled infected erythrocytes to human melanoma cells. PMID- 2209793 TI - Stage-specific adenylate cyclase activity in Trypanosoma brucei. PMID- 2209794 TI - Parasite antigenemia in lymphatic filariasis. PMID- 2209795 TI - Commitment and migration of young neurons in the vertebrate brain. PMID- 2209796 TI - Commitment and migration of young neurons in the vertebrate brain. PMID- 2209797 TI - Principles of neural cell migration. AB - A basic property of immature neurons is their ability to change position from the place of their final mitotic division in proliferative centers of the developing brain to the specific positions they will occupy in a given structure of the adult nervous system. Proper acquisition of neuron position, attained through the process of active migration, ultimately affects a cell's morphology, synaptic connectivity and function. Although various classes of neurons may use different molecular cues to guide their migration to distant structures, a surface-mediated interaction between neighboring cells is considered essential for all types of migration. Disturbance of this cell-cell interaction may be important in several congenital and/or acquired brain abnormalities. The present article considers the basic mechanisms and principles of neuronal cell migration in the mammalian central nervous system. PMID- 2209798 TI - Differential roles of multiple adhesion molecules in cell migration: granule cell migration in cerebellum. AB - The migration of cerebellar granule cells from the external granular layer to the internal granular layer is mediated by the radical Bergmann glial fiber. Recent works have shown that cell adhesion molecules, extra-cellular matrix proteins and proteolytic enzymes or their activators are involved in this process. Immuno localization studies showed differential temporal and spatial expression patterns of different adhesion molecules, their isoforms, and post-translational modification during different stages of granule cell migration. Functional perturbation experiments using cerebellar explant cultures demonstrated that several adhesion molecules as well as plasminogen activator are involved in granule cell migration and are required in different stages. Other systems used to study granule cell migration including dissociated microwell cultures and granule cell deficient mouse mutants are discussed in the context of adhesion molecules. The results accumulated so far suggest that the migration of granule cells is a complex process in which the cooperation of a group of molecules with different functions, some for adhesion some for de-adhesion, are required to fulfill the different needs during the migratory course. PMID- 2209800 TI - Mechanisms of glial-guided neuronal migration in vitro and in vivo. AB - Our laboratory has developed an in vitro model system in which glial-guided neuronal migration can be observed in real time. Cerebellar granule neurons migrate on astroglial fibers by apposing their cell soma against the glial arm, forming a specialized migration junction, and extending a motile leading process in the direction of migration. In vitro assays indicate that the neuronal antigen astrotactin functions as a neuron-glia ligand, and is likely to play a role in the movement of neurons along glial fibers. In heterotypic recombinations of neurons and glia from mouse cerebellum and rat hippocampus, neurons migrate on heterotypic glial processes with a cytology, speed and mode of movement identical to that of neuronal migration on homotypic glial fibers, suggesting that glial fibers provide a permissive pathway for neuronal migration in developing brain. In vivo analyses of developing cerebellum demonstrate a close coordination of afferent axon ingrowth relative to target cell migration. These studies indicate that climbing fibers contact immature Purkinje neurons during the migration and settling of Purkinje cells, implicating a role for afferents in the termination of migration. PMID- 2209799 TI - Extracellular matrix and neuronal movement. AB - During brain development, both neuronal migration and axon guidance are influenced by extracellular matrix molecules present in the environment of the migrating neuronal cell bodies and nerve fibers. Glial laminin is an extracellular matrix protein which these early brain cells preferentially attach to. Extracellular glycosaminoglycans are suggested to function in restricting neuronal cell bodies and axons from certain brain areas. Since laminin is deposited along the radial glial fibers and along the developing nerve pathways in punctate form, the punctate assemblies may be one of the key factors in routing the developing neurons in vivo. This review discusses the role of laminin in neuronal movement given the present concept of the extracellular matrix molecules and their proposed interactions. PMID- 2209801 TI - The specification of neuronal identity in the mammalian cerebral cortex. AB - The determination of neuronal fate in the developing cerebral cortex has been studied by tracking normal cell lineages in the cortex, and by testing the commitment of young cortical neurons to their normal fates. These studies together suggest that neuronal progenitors are multipotent during development and have the potential to produce neurons destined for many or all of the cortical layers. However, the laminar identity of an individual neuron appears to be specified through environmental interactions at the time of the cell's terminal mitotic division, prior to its migration into the cortical plate. PMID- 2209802 TI - Migratory patterns of clonally related cells in the developing central nervous system. AB - Neurons and glioblasts that arise in the ventricular zone migrate to form discrete nuclei and laminae as the central nervous system develops. By stably labeling precursor cells in the ventricular zone, pathways taken by different cells within an individual clone can be described. We have used recombinant retroviruses to label precursor cells with a heritable marker, the E. coli lacZ gene; clones of lacZ-positive cells are later mapped histochemically. Here we review results from three regions of the chicken central nervous system--the optic tectum, spinal cord, and forebrain--and compare them with previous results from mammalian cortex and other regions of the vertebrate CNS. In particular, we consider the relationship between migratory patterns and functional organization, the existence of multiple cellular sources of migratory guidance, and the issue of whether a cell's choice of migratory pathway influences its ultimate phenotype. PMID- 2209803 TI - Cell lineage and cell migration in the developing cerebral cortex. AB - Modern techniques which trace lineages of individual progenitor cells have provided some clues about the processes that determine cell fate in the brain, and have also given us some information about migratory patterns of clonally related cells. In many parts of the central nervous system, progenitors are multipotent; single clones can contain multiple neuronal types or even mixtures of neurons and glia. In addition, one can observe a wide distribution in clone size, even when marking is done in a narrow time window. This suggests that progenitor cells may be fairly plastic and responsive to environmental signals. In the developing cortex, clonally related cells are initially grouped near each other, as in the retina and tectum. However, the subsequent migration of these cells from the ventricular zone to the cortex along glial fibers is accompanied by a progressive dispersion of clonally related neurons. PMID- 2209806 TI - Isolation and characterization of a new hemagglutinin from the red alga Gracilaria bursa-pastoris. AB - A new agglutinin has been isolated from the red alga Gracilaria bursa-pastoris by affinity chromatography on a yeast mannan-Cellulofine column. This agglutinin was isolated as a monomeric glycoprotein with a relatively low molecular weight. It had an isoelectric point of 4.7 and contained large amounts of Gly, Asx and Glx. It agglutinated trypsin-treated rabbit erythrocytes at the low concentration of 30 ng/ml. The activity was inhibited only by glycoproteins bearing N-glycans. This agglutinin also showed mitogenic activity for mouse splenic lymphocytes. PMID- 2209805 TI - The migration of luteinizing hormone-releasing hormone (LHRH) neurons from the medial olfactory placode into the medial basal forebrain. AB - Over the years, investigators have noticed, in a wide variety of species of vertebrates, large numbers of cells migrating from the olfactory placode to the forebrain. These cells were considered to be Schwann cells or ganglion cells of the terminalis nerve. Recently, immunocytochemical localization studies have shown that many of these migrating cells contain luteinizing hormone-releasing hormone (LHRH), a brain peptide that regulates reproductive functions by evoking the release of luteinizing hormone and follicle-stimulating hormone from the anterior pituitary gland. The origin of LHRH cells in the epithelium of the medial olfactory placode, their migration across the nasal septum and into the forebrain, with branches of the terminalis nerve, also a derivative of the medial part of the olfactory placode, has led to some interesting speculations, from evolutionary and physiological perspectives, about the origin of these cells and the role of the terminalis nerve in their migration. PMID- 2209804 TI - Mechanism of neurogenesis in adult avian brain. AB - Adult neurogenesis in birds offers unique opportunities to study basic questions addressing the birth, migration and differentiation of neurons. Neurons in adult canaries originate from discrete proliferative regions on the walls of the lateral ventricles. They migrate away from their site of birth, initially at high rates, along the processes of radical cells. The rates of dispersal diminish as the young neurons invade regions devoid of radial fibers, probably under the guidance of other cues. The discrete sites of birth in the ventricular zone generate neurons that end up differentiating throughout the telencephalon. New neurons may become interneurons or projection neurons; the latter connect two song control nuclei between neostriatum and archistriatum. Radial cells, that in mammals disappear as neurogenesis comes to an end, persist in the adult avian brain. The presence of radial cells may be key to adult neurogenesis. Not only do they serve as guides for initial dispersal, they also divide and may be the progenitors of new neurons. PMID- 2209807 TI - Ascorbic acid stimulates production of glycosaminoglycans in cultured fibroblasts. AB - The effect of ascorbic acid on collagen synthesis is well characterized. Proteoglycans and their attached glycosaminoglycans are components of the extracellular matrix closely associated with collagen fibers. We examined whether ascorbic acid also plays a role in glycosaminoglycan production. Synthesis and deposition of glycosaminoglycans into the extracellular matrix and secretion into the media were followed in human skin fibroblasts cultured in the presence and absence of ascorbic acid. Specific glycosaminoglycans were identified and quantitated by differential enzyme digestion, ion-exchange column chromatography, and cellulose-acetate electrophoresis. No major qualitative changes in glycosaminoglycans were observed. However, quantitatively, synthesis of glycosaminoglycans increased 30 to 90%, and deposition into the extracellular matrix increased 80% in the presence of ascorbic acid. This effect was only in part secondary to decreased levels of collagen, and the diminished capacity of underhydroxylated collagen to bind proteoglycans. The effect of ascorbic acid on extracellular macromolecules is thus more pervasive than previously assumed. PMID- 2209808 TI - Interaction of anthracyclinic antibiotics with cytoskeletal components of cultured carcinoma cells (CG5). AB - The effects of doxorubicin (adriamycin, ADR) and daunorubicin (daunomycin, DAU), two anthracyclinic antibiotics, on a human breast carcinoma cell line (CG5) were studied by cytochemical and morphological methods. Both ADR and DAU were capable of inducing the multinucleation and spreading phenomena, associated with a decrease of the cell growth rate. DAU appeared to be more effective than ADR at the tested concentrations (10(-5), 5 x 10(-5) mM), in affecting the cell growth as well as in inducing multinucleation. As revealed by scanning electron microscopy, spreading and multinucleation were accompanied by a remarkable redistribution of surface structures. Moreover, a dose- and time-dependent rearrangement of the underlying cytoskeletal components was clearly detected. In addition, both ADR and DAU at 5 x 10(-5) mM seemed to favor the rebuilding of microtubules after treatment with colcemid, while a higher dose (10(-4) mM) exerted the opposite effect. Furthermore, both anthracyclines prevented the action of the antimicrotubular agent. When recovered after treatment with cytochalasin B, in presence of ADR (or DAU) (5 x 10(-5), 10(-4) mM), cells showed a microfilament pattern rearranged differently as compared to that of cells recovered in anthracycline-free medium. The results reported here strongly suggest the involvement of actin and tubulin in CG5 cell response to ADR and DAU treatments. Thus, the cytoskeletal apparatus is confirmed as another target involved in the mechanism of action of anthracyclines. PMID- 2209809 TI - Application of X-ray microanalysis to the study of drug uptake in cell culture. AB - X-ray microanalysis has been used previously to study the accumulation of iodine in alveolar macrophages of rats treated with the iodinated drug, amiodarone. Due to metabolism of the drug in vivo, primarily to desethylamiodarone, it was not possible to identify the source of the iodine signal. In the present study we have utilized primary cell cultures of alveolar macrophages to study the intracellular accumulation of each of these drug species in vitro. Neither drug is metabolized by these cells in culture, permitting characterization of the accumulation of each independent of the other. Cells were incubated with equimolar concentrations of either amiodarone or desethylamiodarone for 42 hr, and X-ray microanalysis of freeze-dried cryosections of cells was used to quantify accumulation by monitoring the iodine signal associated with each drug. For both drug exposures, the highest iodine content was present in amorphous bodies and dense granules, consistent with the pattern following in vivo exposure. Higher levels of desethylamiodarone, compared to amiodarone, were measured in all compartments of the cells. The results of the in vitro investigation further demonstrate the utility of X-ray microanalysis in the study of the cellular response to amiodarone and desethylamiodarone. PMID- 2209811 TI - Horseradish peroxidase as a permeability marker in injured rat caudal and iliac arteries. AB - The permeability to Horseradish Peroxidase (HRP) of the rat caudal artery at the level of spontaneous lesions was evaluated by electron microscopy and compared with that of lesions experimentally induced by pinching or internal scraping of the caudal and iliac arteries. No HRP reaction product is observed in the extracellular space of the arterial wall when (i) the internal elastic lamina (IEL) and the endothelium are absent, (ii) the IEL is maintained and the endothelium is absent and (iii) the IEL is absent and the endothelium has regenerated. That HRP does enter the arterial wall in cases of gross endothelial damage is shown by its selective retention in damaged smooth muscle cells in such cases. In contrast, HRP reaction product is detected in the subendothelial space when the IEL is maintained and is covered by a regenerating or recently regenerated endothelium. Furthermore, the amount of tracer visualized under the same experimental conditions is greater in the iliac than in the caudal artery. We conclude that the detection of HRP in the subendothelial space of the artery wall requires the presence of regenerating or recently regenerated endothelial cells lying on an intact IEL. It is thus not simply related to endothelial permeability but depends also upon the retention of HRP by extracellular substances. In addition, the quantity of marker retained varies between different sites in the arterial tree. PMID- 2209810 TI - Aortic calcification in chronic fluoride poisoning: biochemical and electronmicroscopic evidence. AB - Fluoride is known to cause ectopic calcification. The biochemical mechanism(s) involved in the initiation of calcification is not understood and the accompanying ultrastructural changes remain to be elucidated. Therefore, certain relevant parameters have been investigated in the aorta of rabbits administered fluoride, 10 mg NaF/kg body wt, every 24 hr for 17 and 24 months. The significant findings are: (i) degeneration of smooth muscle fibers in the tunica media of the aorta, (ii) presence of electron-dense granules in the mitochondria and on the inner surface of the plasma membrane of smooth muscle cells, (iii) presence of matrix vesicles with electron-dense deposits, (iv) enhanced calcium content and the Ca/P ratio, and (v) increased total glycosaminoglycan (GAG) content with reduced dermatan sulfate. The presence of electron-dense granules in the mitochondria, on the plasma membrane and matrix vesicles is suggestive of the process of calcification. The enhanced calcium content as well as the Ca/P ratio supports the view that the aorta is undergoing mineralization. The total GAG is enhanced, possibly due to an increase in the content of GAGs other than isomers of chondroitin. The observation that conveys an important message is that the dermatan sulfate normally known to exist in high concentrations in soft tissues begins to decrease as the process of calcification sets in. This perhaps would hold true and may serve as an index in the process of ectopic calcification. PMID- 2209812 TI - A longitudinal study of class and subclass antibody response to pneumococcal vaccination in splenectomized individuals with special reference to patients with Hodgkin's disease. AB - Antibody class and subclass response to pneumococcal vaccination was monitored in 173 splenectomized individuals. The distribution according to indication for splenectomy was Hodgkin's disease (HD; n = 41), non-Hodgkin lymphoma (NHL; n = 25), autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (n = 17), accidental splenectomy during abdominal surgery for malignant (AMA; n = 15) and benign (ABE; n = 42) disease and splenectomy due to splenic rupture caused by trauma (TRAUMA; n = 33). Pre-vaccination total IgG pneumococcal antibody values (i.e. against the whole antigen = the vaccine) in the NHL patients were lower than in the ABE and TRAUMA groups (p less than 0.05). The response to vaccination in HD and NHL patients did not differ from that in the other patient groups. Furthermore, pre-vaccination values did not differ between HD patients vaccinated before splenectomy and treatment and those vaccinated after, although the former group showed a better response to vaccination (p less than 0.05). HD and TRAUMA patients were followed by serial serum sampling. The antibody values declined to pre-treatment levels after 3 years but no differences either between HD and TRAUMA patients or between HD patients vaccinated before or after splenectomy and treatment were observed with regard to antibody decrease. It is concluded that pneumococcal antibody levels increased in all splenectomized patient groups following vaccination. The pattern of the antibody decline motivates revaccination studies in patients 2 yr post-immunization. PMID- 2209813 TI - Danazol therapy in chronic immune thrombocytopenic purpura. PMID- 2209814 TI - Autoimmune haemolytic anaemia and idiopathic pulmonary fibrosis associated with HLA-B27 antigen. PMID- 2209815 TI - Congenital dyserythropoietic anaemia (CDA) with intrauterine symptoms and early lethal outcome. PMID- 2209816 TI - Persistent generalized lymphadenopathy (transfusion-related) in an HIV seropositive heterosexual man with sickle-cell beta-thalassemia. PMID- 2209817 TI - Significance of bone marrow sideroblastosis in myelodysplastic syndromes. PMID- 2209818 TI - Haemoglobin-E trait and the clinical course of malaria in Thai soldiers. PMID- 2209820 TI - Idiopathic myelofibrosis: a review. PMID- 2209819 TI - Cytokines and DIC in acute leukaemia. PMID- 2209821 TI - Patchy haemopoiesis in long-term remission of idiopathic aplastic anaemia. AB - 13 patients with idiopathic aplastic anaemia in remission for more than 2 years were examined to define the haemopoietic status by means of bone marrow scintigraphy, ferrokinetics and bone marrow culture for haemopoietic progenitor cells. Haemoglobin levels reached the normal range in all these patients although mild neutropenia and thrombocytopenia were still observed in 5 patients. Bone marrow scintigrams using indium-111 showed normal distribution in 2, diffuse low accumulation in 3, patchy distribution in 7, and expanded distribution with patchy uptake in 1 patient. The defective haemopoiesis was also confirmed by ferrokinetic and bone marrow culture studies. The patchy haemopoiesis appears to characterize the residual marrow damage in remission of idiopathic aplastic anaemia. PMID- 2209822 TI - Cancer procoagulant in acute lymphoblastic leukemia. AB - In a previous study we characterized cancer procoagulant (CP), a 68 kd cysteine proteinase which directly activates coagulation factor X in various subtypes (from M1 to M5) of acute non-lymphoblastic leukemia (ANLL). The aim of this study was to determine whether CP is also expressed by acute lymphoblastic leukemia (ALL) cells. Blasts from 25 ALL patients were extracted and tested for their procoagulant properties. 16 samples (64%) shortened the recalcification time of normal human plasma, and 9 (36%) did not. 8 of the 16 active samples showed properties compatible with CP, i.e. independence from factor VII in triggering blood coagulation and sensitivity to cysteine proteinase inhibitors. Selected samples also cross-reacted with a polyclonal antibody raised against purified CP. The specific activity of CP in ALL extracts was significantly lower than in most ANLL types previously studied (all but M4). These finding indicate that CP can be a property of the lymphoid phenotype although its expression may be lower than in the myeloid phenotype. PMID- 2209823 TI - Low incidence of bleeding from HIV-related thrombocytopenia in drug addicts and hemophiliacs: implications for therapeutic strategies. AB - The records of 608 intravenous drug addicts and 124 hemophiliacs diagnosed in 1985 to be seropositive for HIV were reviewed to identify patients with thrombocytopenia. The records of 54 drug addicts (8.9%) and 14 hemophiliacs (11.2%) who had chronic thrombocytopenia were then followed through June 1989 to estimate the incidence of bleeding episodes. The records of 55 HIV-seronegative patients with idiopathic thrombocytopenic purpura (ITP), comparable for age, platelet count at diagnosis and duration of follow-up, were used for comparison. Patients with ITP were significantly different from those with HIV-associated thrombocytopenia in having a higher proportion of females (M/F ratio 13/42 v 53/15, p less than 0.001) and more intensive treatment (treated: 62% v 21%, p less than 0.001; splenectomized 37% v 1.5%, p less than 0.001). The incidence of major bleeding was not significantly different in drug addicts, hemophiliacs and ITP patients (0.98, 1.82 and 1.17/100 patients/year). Among drug addicts, bleeding was significantly more frequent in women than in men (3.4 v 0/100 patients/year, p less than 0.05). Our results indicate that the incidence of major bleeding in patients with HIV-associated thrombocytopenia is low and similar to that observed in more intensively treated ITP patients. PMID- 2209824 TI - Tranexamic acid therapy in acute myeloid leukemia: possible reduction of platelet transfusions. AB - We studied the clinical efficacy and safety of the antifibrinolytic drug tranexamic acid (TA) in patients undergoing chemotherapy for acute leukemia. 54 newley diagnosed AML patients were treated with 1 g of TA every 6 hours until the platelet count rose to above 20 x 10(9)/l. Platelet transfusions were given, irrespective of the count, only when oral, mucosal or significant skin bleeding manifestations were observed. During induction, the average number of days with thrombocytopenia below 20 x 10(9)/l was 14.4 +/- 7.4 and 4.6 +/- 4.1 transfusions were given in each course. During consolidation, the average number of thrombocytopenic days was 8.4 +/- 8.5 and only 1.7 +/- 1.8 transfusions were administered. In 11.5% of the induction and 32.1% of the consolidation courses, no platelet support was required. TA was tolerated very well and no side effects or thromboembolic complications were observed. Only in 6 of the 78 induction courses did a major bleeding event occur and there were none in any of the 53 consolidation courses. Thus it seems that TA therapy allowed a significant reduction in the use of platelet transfusions without submitting the patients to greater bleeding risks. PMID- 2209825 TI - Acute lymphoblastic leukemia in the elderly. AB - We report our findings in 18 patients with acute lymphoblastic leukemia (ALL) aged 60 years or older. A preleukemic syndrome was observed in 2 patients. Compared to younger adults with ALL, L3 morphology was unexpectedly frequent (4/16). T-ALL was not observed. Other criteria of poor prognosis (high white blood cell count, CNS involvement, organomegaly, high serum LDH) were similar to those reported in young adults. 12 patients were treated with an OPAL-derived regimen, 4 with the MAV regimen, 1 with vincristine and prednisone, 1 with 6 mercaptopurine. Complete remission was achieved in 8 patients but proved short lived. 5 patients died in aplasia and 5 failed to achieve remission. Median survival for the whole group was 3 months. ALL in the elderly raises the dilemma of an aggressive disease in patients with poor tolerance to intensive therapy. PMID- 2209827 TI - Anticipatory loss: a family systems developmental framework. AB - This article provides a family-systems developmental framework for anticipatory loss in situations of physical illness, disability, and long-term psychiatric disorders, and offers a conceptual base for theory building, clinical practice, and research. A family systems-illness model that integrates psychosocial types and phases of illness with family variables, in particular, developmental patterns and beliefs systems, provides a foundation to rethink and expand our approaches to threatened loss. PMID- 2209826 TI - Risk assessment in myelodysplastic syndromes: value of clinical, hematologic and bone marrow histologic findings at presentation. AB - We analyzed the prognostic value of clinical, hematologic and bone marrow (BM) histologic findings at presentation in 94 patients with myelodysplastic syndromes (MDS) (28 RA; 2 RARS; 34 RAEB; 6 CMML; 24 RAEB-t). With survival as the dependent variable, stepwise multivariate analysis indicated as the prognostically most important factors among the MDS taken as a whole: latency from the first symptoms to diagnosis, age, and percentage of BM blasts. In each main MDS group the most unfavorable initial characteristics were: 1) low Hb, no macro-megaloblastosis, male sex for RA/RARS; 2) low Hb and low platelet levels for RAEB/CMML; 3) granuloblastic hyperplasia and high BM blastosis for RAEB-t. Of the BM histologic parameters, only the percentage of blasts had significant prognostic value. Histologic assessment of BM blastosis, however, did not differ statistically from that based on cytologic examination of BM smears, so that marrow histology seemed not essential for initial prognostic assessment in MDS patients. The finding of abnormal localization of immature precursors (ALIP) in BM biopsies was associated with a negative trend without reaching statistical significance. Using four objective parameters of proven significance (age, Hb, platelets, and BM blasts) we devised a staging system of immediate clinical utility for prognostic stratification and risk-adapted therapeutic choices. PMID- 2209828 TI - Predictors of depression in caregivers of dementia patients: boundary ambiguity and mastery. AB - This study examined the role of two perceptual variables in predicting the development of depressive symptoms in caregivers. The first, boundary ambiguity, refers to whether the dementia patient is perceived as psychologically in or out of the family system. The second, an orientation toward mastery, is related to how persons manage various stressful situations, including caring for a dementia patient. This study included 70 patients and their caregivers. Stepwise regression and path analytic techniques were used to compare the impact of variables related to the illness per se and of variables related to caregivers' perceptions of their situations. Results indicate that both perceptual variables, boundary ambiguity, and mastery, are significantly related to a caregivers' depression level whereas severity of the patient's dementia is not. In sum, the more a caregiver perceives a mate as psychologically absent, the less masterful and the more depressed she or he is. PMID- 2209829 TI - The therapeutic use of self in constructionist/systemic therapy. AB - The introduction of a constructivist orientation to family therapy has promoted a reconceptualization of the therapeutic use of self. The multiply-engaged therapist is seen as positioned within rather than as acting upon a system. Such a therapist facilitates change through participation in, and active engagement with, each system member's perceptions and experience. Multiple engagement synthesizes the "instrumental" and "noninstrumental" perspectives through use of the idea of systemic influence, or systemic positioning. Multiple engagement stresses the relational perspective over the extremes of either pure interventionism or pure facilitation. Five specific therapeutic stances are introduced and are clinically illustrated; taken together, these stances articulate one model for a constructivist family therapy. PMID- 2209830 TI - Reflections during a study on family therapy with drug addicts. AB - This article presents ideas and reflections emerging during a project on family therapy with drug abusers. Initially inspired by the writings of Stanton and Todd on the subject, the project developed into a recursive and self-reflective process, characterized by increasing doubts about the usefulness of categorization of families, of pre-planning therapy, and of the therapist as an "expert." The limitations of approaches that emphasize the importance of understanding the family structure as the basis for changing it are discussed, particularly with respect to how they decrease therapist flexibility and may block the family's finding their own solution. Alternative approaches to practice and research are also discussed, bearing on ideas particularly formulated by theoreticians and practitioners inspired by second-order cybernetics. PMID- 2209831 TI - Session-intersession sequences in the treatment of chronic anorexic-bulimic patients: following the model of "family games". AB - In this article, the author presents some technical aspects of a psychotherapeutic approach for treating chronic anorectic patients. Two basic principles underlie the approach. First, the main purpose of the treatment is to improve the patient's relational skills in order to enable her to cope with her family's "game". Second, the therapeutic relationship is considered hierarchically subordinate to her relationships outside the therapeutic context. Mastering the model of families with anorectics is essential if the therapist is to be consistent with these principles. Specialized training in verbal and nonverbal communication is considered a useful tool. PMID- 2209832 TI - Six characters in search of an author: a constructivist view. AB - The investigation of imaginative literature has been one of psychotherapy's most useful tools for the explication of its theories and the general dissemination of psychotherapeutic concepts. Using this idea, I examine Luigi Pirandello's play Six Characters in Search of an Author from a constructivist, family therapy, point of view. PMID- 2209833 TI - A test of the Olson Circumplex Model: examining its curvilinear assumption and the presence of extreme types. AB - The debate over the usefulness of different family models continues. Recent attention has been paid to comparisons between the Olson Circumplex Model and the Beavers Systems Model. The present study seeks to contribute evidence that bears directly upon one of the most fundamental points of controversy surrounding the Olson model--the linear versus curvilinear nature of the cohesion and adaptability dimensions. A further contribution is an examination of the actual occurrence of the Circumplex Model's extreme types in a clinical population. PMID- 2209834 TI - Intergenerational effects of the Holocaust: patterns of engagement in the mother daughter relationship. AB - The present study explored the quality of engagement between mothers and adult daughters. Daughters of Holocaust survivors, European immigrants, and nonimmigrants were compared on mothers' protectiveness and care during their daughters' first 16 years, and on daughters' individuation from the family of origin. The survivor group perceived themselves as less individuated from both their parents than the other two groups. However, daughters in the three groups reported feeling equally intimate with their parents. There were no significant group differences found on intergenerational intimidation or competing loyalties. There was a tendency for mothers in the survivor group to be perceived as more indulgently protective. These findings suggest that the relationship between survivor mothers and their daughters may be characterized by a lower degree of individuation, though not at the cost of intimacy. PMID- 2209835 TI - Assessment of resectability of carcinoma of the pancreatic head by ultrasonography and computed tomography. A retrospective analysis. AB - In order to establish the reliability of the assessment of tumour stage and hence of resectability of carcinoma of the pancreatic head by ultrasonography (US) and computed tomography (CT) a retrospective analysis was performed on 41 patients. Both direct imaging techniques were very accurate in detecting non-resectable disease, 100 and 85% respectively, but were much less accurate in predicting resectable cancer, 18 and 15% respectively. False-resectable results were established in 58% of US examinations and 42% of CT examinations. As demonstrated in this study, predicting resectability of carcinoma of the pancreatic head with US and CT is an inadequate method of assessing tumour stage and should be complemented by other techniques to ensure a reliable result. PMID- 2209836 TI - Underdiagnosis of carcinoma of the stomach in the elderly: a 25-year autopsy study. AB - Gastric carcinoma may present atypically in the elderly. Between 1955 and 1979, 571 autopsies on gastric carcinoma cases were carried out at the Gade Institute, Bergen. In 165 of them the diagnosis had not been made clinically. The latter patients were, on average, 10 years older at death than those in whom the diagnosis was made premortem, and their tumours were smaller. In 45 the tumour was considered an incidental autopsy finding, while 58 were diagnosed clinically as advanced cancer of unknown origin. In the remaining 62 cases the cancer was the underlying cause of death. Recognition of an elderly sub-group of patients whose gastric carcinomas presented atypically brings with it an increasing diagnostic challenge in our ageing population. PMID- 2209837 TI - A pilot randomized control trial of proglumide (a gastrin receptor antagonist) in advanced colorectal cancer. AB - Forty-one patients with advanced colorectal cancer were entered into a randomized controlled trial of treatment with proglumide--a gastrin receptor antagonist. There was no difference in survival between the treated and the untreated groups of patients, although there was a trend towards increased survival in those treated patients with hepatic metastases alone. Proglumide does not cause regression in advanced colorectal cancer but larger studies would be required to detect an effect on tumour growth. PMID- 2209839 TI - Radiation therapy for locally advanced breast cancer: prognostic factors and complication rate. AB - A retrospective analysis was carried out in 100 patients with locally advanced breast cancer without distant metastases treated by radiotherapy between 1960 and 1979. The primary tumor was irradiated to a total dose of 60 Gy in 76 patients and to doses ranging between 60 and 80 Gy in 24 patients. The regional lymphatics were treated with doses between 50 and 60 Gy. Following radiotherapy, chemotherapy was administered to 58 patients and hormonal therapy to 29, while 13 patients received no further therapy. Locoregional recurrences were documented in 29% and distant metastases in 49% of patients. The actuarial survival was 56% at 5 years, 21% at 10 years and 14% at 15 years. At 10 years 90% of the surviving patients had some degree of radiation damage. PMID- 2209838 TI - Early second surgery in ovarian cancer--improving the potential for cure or another unnecessary operation? AB - The presence and amount of residual disease after primary surgery is a major adverse prognostic factor in epithelial ovarian cancer [EOC]. Rapid initial cytoreduction employing second surgery early in the primary chemotherapeutic management of patients with gross residual disease has been advocated as a means of improving outcome. To evaluate the prognostic value of such an approach we have reviewed the outcome of 24 patients with gross residual disease, who were debulked to less than 2 cm residuum at a second operation, performed after three cycles of cis-platinum-based chemotherapy (a median of 14 weeks from the initial laparotomy), and compared this with an historical series of 195 patients with residual disease (70 patients with less than 2 cm residuum) who received cis platinum but no early secondary surgery. In the control series, stage and residual disease status were important prognostic factors. There was no significant difference in patient or disease characteristics between those patients in the early second surgery group and control patients with greater than 2 cm disease (n = 125). Initially the survival curve for the early second surgery group was similar to the less than 2 cm disease group, but at about 18 months, there was a rapid deterioration until the survival parallels that of the patients with bulky disease at presentation. Early secondary surgery did not significantly prolong survival in patients with greater than 2 cm of residual disease. PMID- 2209840 TI - Thyroid carcinoma in Nigeria: review of management. AB - The records of 54 patients with thyroid carcinoma who were managed at the Department of Radiation Biology and Radiotherapy, Lagos University Teaching Hospital between 1973 and 1985 were reviewed. Most of the patients lived in the goitre-endemic belt of Southern Nigeria even though only about 14% of them were found to have had treatment in the past for what was considered to be benign thyroid enlargement. The predominant histological type was follicular carcinoma, which represented 42.9%; the female to male ratio was 2.9 to 1. Surgery, which was the initial treatment of these patients, was limited to the amount of disease present at operation in most cases so as to limit postoperative complications. The indications for other treatments employed which included radiotherapy, radioactive iodine therapy and postoperative suppression with thyroxine are discussed. Forty-eight percent of all the patients developed recurrence after treatment while 88% of these patients with recurrence had distant metastases. The 5-year survival rate was 43% after which many patients were lost to follow-up. PMID- 2209841 TI - Brain metastases in patients with well-differentiated thyroid carcinoma: study of 11 cases. AB - Eleven patients, three males and eight females, developed brain metastases from well-differentiated thyroid carcinoma 1 to 20 years after their original diagnosis. Two had brain metastases only and nine had metastases to the lungs and bones as well. Most patients died within a year of diagnosis of brain metastases. We conclude that brain metastasis from thyroid carcinoma carries a poor prognosis and that newer modalities of therapy may be needed. PMID- 2209842 TI - Thyroid cancer causing death after 40 years: rationale for initial intensive treatment. AB - Three cases of death after 40 years of differentiated thyroid cancer are presented. Prolonged follow-up identified relapses in patients assumed to have been cured. Thus the case is argued for intensive initial therapy comprising near total thyroidectomy (including excision of any macroscopic nodal disease) and ablative iodine-131 therapy in addition to thyroid hormone suppression. PMID- 2209843 TI - Massive haemoperitoneum complicating metastasis in the liver. AB - The rare phenomenon of gross intra-abdominal bleeding due to hepatic metastasis was seen in a young male who a short time before had undergone orchiectomy because of embryonal cell carcinoma. Following laparotomy, 4 liters of fresh blood were drained from the peritoneal cavity and the left lobe of the liver, containing a single large metastasis, was removed. It is stressed that when no other cause of such haemorrhage can be found in a patient known to have had malignancy, the possibility of bleeding from a metastasis should be considered and appropriate measures taken. PMID- 2209845 TI - Ag NORs in evaluation of neo-adjuvant chemotherapy for gastric adenocarcinoma. PMID- 2209844 TI - A comparison of regional and systemic chemotherapy for hepatic metastases. AB - A 48-year-old man with colorectal liver metastases underwent insertion of an hepatic arterial infusion catheter for regional chemotherapy. Postoperative hepatic arterial perfusion scintigraphy showed that only part of the liver was being perfused by this route. Chemotherapy was administered weekly via the catheter. In effect, part of the liver received regional chemotherapy, whereas the remainder of the organ was exposed to systemic chemotherapy. Ultrasonography demonstrated shrinkage of the metastases in the area of liver receiving regional therapy, whereas disease progression occurred in the region of liver receiving 'systemic' treatment. This patient demonstrates that tumour may respond to regional chemotherapy despite disease progression on systemic therapy and suggests that a controlled trial would yield valuable data. PMID- 2209846 TI - Silicone and breast cancer. PMID- 2209847 TI - [Measures for the prevention of AIDS in medical institutions]. PMID- 2209848 TI - [The characteristics of the examination of children suffering from gynecological diseases]. PMID- 2209849 TI - [The diagnosis and treatment of acute stenosing laryngotracheitis and laryngotracheobronchitis in children at the prehospital stage]. PMID- 2209850 TI - [Epiphysiolysis of the femur head in children]. PMID- 2209851 TI - [Neurocirculatory dystonia]. PMID- 2209852 TI - [International Child Protection Day]. PMID- 2209853 TI - [Melanoma of the skin]. PMID- 2209854 TI - [Overheating syndromes in miners]. PMID- 2209855 TI - [Balneo- and thermotherapy of diseases of the locomotor apparatus]. PMID- 2209856 TI - [Resuscitation in drowning]. PMID- 2209857 TI - [Antianginal agents]. PMID- 2209858 TI - [Laxative agents]. PMID- 2209859 TI - [Insurance medicine for workers in ship-building plants]. PMID- 2209860 TI - [The methodology of epidemiological proof]. PMID- 2209861 TI - [The provision of radiation safety for patients during the x-ray therapy of keloid scars]. PMID- 2209862 TI - [Candidiasis of the urogenital system in women]. PMID- 2209863 TI - [The differential diagnosis of pains in the area of the heart]. PMID- 2209864 TI - [Legislation on work and health protection for the future mother]. PMID- 2209866 TI - [Ultrasonic diagnosis in surgery]. PMID- 2209867 TI - [Basalioma of the skin]. PMID- 2209865 TI - [Iron-deficiency anemia]. PMID- 2209868 TI - [Trigger points]. PMID- 2209869 TI - [Smoking and cancer]. PMID- 2209870 TI - [Premature rupture of the fetal membranes]. PMID- 2209871 TI - [The gastralgic variant of myocardial infarct]. PMID- 2209872 TI - [Inflammation of the adnexa uteri, ovarian dysfunction, secondary infertility]. PMID- 2209873 TI - [Medical ethics and deontology in childhood gynecology]. PMID- 2209874 TI - Fertility after contraception or abortion. AB - There is a very small correlation, if any, between the prior use of OCs and congenital malformations, including Down's syndrome. There are few, if any, recent reports on masculinization of a female fetus born to a mother who took an OC containing 1 mg of a progestogen during early pregnancy. However, patients suspected of being pregnant and who are desirous of continuing that pregnancy should not continue to take OCs, nor should progestogen withdrawal pregnancy tests be used. Concern still exists regarding the occurrence of congenital abnormalities in babies born to such women. The incidence of postoperative infection after first trimester therapeutic abortion in this country is low. However, increasing numbers of women are undergoing repeated pregnancy terminations, and their risk for subsequent pelvic infections may be multiplied with each succeeding abortion. The incidence of prematurity due to cervical incompetence or surgical infertility after first trimester pregnancy terminations is not increased significantly. Asherman's syndrome may occur after septic therapeutic abortion. The pregnancy rate after treatment of this syndrome is low. The return of menses and the achievement of a pregnancy may be slightly delayed after OCs are discontinued, but the fertility rate is within the normal range by 1 year. The incidence of postpill amenorrhea of greater than 6 months' duration is probably less than 1%. The occurrence of the syndrome does not seem to be related to length of use or type of pill. Patients with prior normal menses as well as those with menstrual abnormalities before use of OCs may develop this syndrome. Patients with normal estrogen and gonadotropin levels usually respond with return of menses and ovulation when treated with clomiphene. The rate for achievement of pregnancy is much lower than that for patients with spontaneous return of menses. The criteria for defining PID or for categorizing its severity are diverse. The incidence of PID is higher among IUD users than among patients taking OCs or using a barrier method. The excess risk of PID among IUD users, with the exception of the first few months after insertion, is related to sexually transmitted diseases and not the IUD. Women with no risk factors for sexually transmitted diseases have little increased risk of PID or infertility associated with IUD use. There appears to be no increased risk of congenital anomalies, altered sex ratio, or early pregnancy loss among spermicide users. All present methods of contraception entail some risk to the patient. The risk of imparied future fertility with the use of any method appears to be low.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2209875 TI - Falloposcopy: frontiers realized ... a fantastic voyage revisited. PMID- 2209876 TI - Exogenous estrogen therapy for treatment of clomiphene citrate-induced cervical mucus abnormalities: is it effective? AB - Clomiphene citrate (CC) may have an adverse effect on cervical mucus (CM) quality and quantity. A placebo-controlled study was performed to assess the effect of exogenous follicular phase estrogen (E) on CM. Subjects qualified for inclusion by repeated demonstration of poor CM while on CC therapy as judged by spinnbarkeit, quantity, and viscosity. Subjects were treated by a randomized, placebo-controlled format using: (1) oral micronized estradiol (E2), 2 mg; (2) conjugated Es, 5 mg, or (3) placebo administered on cycle days 9 to 14. Cervical mucus was scored blindly during therapy within 48 hours before ovulation. Twelve subjects were observed through 36 treatment cycles with mean (+/- SD) CM scores: micronized E2, 4.2 +/- 1.8; conjugated Es, 4.3 +/- 1.7; and placebo, 4.7 +/- 2.9. There was no significant difference in mean values (P = 0.96, analysis of variance) or frequency of CM score greater than 4 (P = 0.85, Fisher exact test). We conclude that therapy with the E preparations tested did not improve the quality or quantity of CM in CC-treated patients. PMID- 2209877 TI - Treatment of tubal pregnancy by local injection of methotrexate after adrenaline injection into the mesosalpinx: a report of 25 patients. AB - Twenty-five patients with a tubal pregnancy were treated by an injection of methotrexate (MTX) into the tubal swelling after vasoconstriction of the mesosalpinx with adrenaline. Twenty-four of the 25 patients had an uneventful clinical course. In one case, the tube ruptured despite falling serum human chorionic gonadotropin (hCG) concentrations. In 17 of 24 patients, the dose of 100 mg that was locally injected was sufficient. Seven patients were given additional systemic injections. In 3 of the 4 patients with high initial serum hCG levels (greater than 10.000 mIU/mL), the clinical course was uneventful. The side effects of MTX and adrenaline were minimal. Whether this way of treatment guarantees better chances of fertility in the future is unknown. Therefore a prospective, case-controlled study comparing the fertility rates in different ways of treatment is needed. PMID- 2209878 TI - The effect of metoclopramide on ovarian responsiveness to gonadotropin administration in patients with severe polycystic ovarian syndrome. AB - Six patients with poor ovarian response to menotropin after pretreatment with a gonadotropin-releasing hormone analog exhibited improved ovarian responsiveness when metoclopramide was added on days 3, 5, and 7 of the cycle. This was evidenced by a higher number of leading follicles (4.4 versus 0.6), a higher mean of maximal serum 17 beta-estradiol levels (560 versus 178 pg/mL), a shorter duration of menotropin treatment (7 versus 11 days), and fewer ampules of menotropin used (20 versus 37 ampules/cycle) in metoclopramide-treated cycles as compared with control cycles, respectively. Serum prolactin levels reached a maximum of 172 ng/mL within 1 hour after metoclopramide administration and declined to normal range within 6 hours. These results suggest that intermittent increased prolactin secretion may augment ovarian response to gonadotropins. PMID- 2209879 TI - Aromatase activity of human granulosa cells in patients with polycystic ovaries treated with dexamethasone. AB - The effect of dexamethasone (DEX) (9 alpha-Fluro-16 alpha-methyl prednisolone) on secretion of steroids by human granulosa luteinized cells was studied by culturing cells from mature follicles of women with polycystic ovarian disease and treated for infertility in the in vitro fertilization program. Patients were treated with DEX 0.5 mg/d until the day of human chorionic gonadotropin administration. The cells were cultured for 24 hours in the presence of androstenedione (10(-7)M). After incubating for 24 hours, the medium was replaced and the cells were incubated for an additional 24 hours. The medium was then harvested and assayed for estradiol (E2) and progesterone (P). Results were compared with those of a control group who was not treated with DEX. Estradiol production by cells was significantly lower in the study group treated with DEX. Progesterone production was not influenced by DEX. Follicular fluid levels, E2, and androgens did not vary with DEX treatment, whereas cortisol levels markedly decreased and P levels increased with the treatment. These findings suggest that glucocorticosteroids can directly influence granulosa luteinized cell function. PMID- 2209880 TI - Luteinizing hormone and human chorionic gonadotropin receptors in human corpora lutea from clomiphene citrate-induced cycles. AB - Midluteal phase corpora lutea (CL) obtained from women induced with 50 mg (n = 5), 100 mg (n = 5), and 150 mg (n = 5) of clomiphene citrate (CC) were measured for luteinizing hormone/human chorionic gonadotropin (LH/hCG) concentrations and cytosol progesterone (P) and 17 alpha-hydroxyprogesterone (17-OHP) and compared with midluteal phase CL from eight normal women (controls). More CL (26) that were significantly heavier (2.0 +/- 0.3 g, [mean +/- SEM]) were obtained with CC than in controls (10). Clomiphene citrate treatment increased LH/hCG receptor concentrations and the dissociation constant significantly from 69 +/- 12 fmol/mg protein and 1.1 +/- 0.2 x 10(-10) M, respectively, in controls to 112 +/- 6 fmol/mg protein and 2.1 +/- 0.1 X 10(-10) M. Cytosol P and 17-OHP levels were not significantly increased. Cumulatively these cellular effects may be responsible for increasing serum P and responsiveness to hCG and for correcting luteal dysfunction. PMID- 2209881 TI - Spectrophotometric analysis of follicular fluid related to oocyte fertilization, embryo cleavage, and follicular fluid protein and hormone content. AB - Spectrophotometric absorbance patterns of follicular fluids (FF) obtained from in vitro fertilization patients were analyzed and compared with oocyte fertilization and embryo cleavage rates. Each absorbance pattern was resolved into three components: delta OD360, delta OD415, and delta OD455. A positive correlation was found between fertilization outcome and delta OD455. The absorbances were not related to embryo cleavage rates. We confirmed the presence of bilirubin and beta carotene in FF: these pigments absorb at 455 nm and are most likely serum derived. To explain the association between delta OD455 and fertilization, we hypothesized that the FF delta OD455 is a marker of the degree of vascularization of the follicle that could be assessed by FF protein and hormone concentrations. However, no correlation was found between the delta OD455 and these FF parameters, suggesting an alternative explanation for this association. PMID- 2209882 TI - Melatonin and the ovulatory luteinizing hormone surge. AB - A newly developed 125I-radioimmunoassay allows for the accurate determination of physiological concentrations of plasma melatonin. Melatonin secretion does not change significantly on the day before and the day of the luteinizing hormone (LH) surge when compared with the early follicular phase. In addition, it was confirmed that the beginning of the LH surge frequently occurs in the morning and is associated with low melatonin values (six of nine women). Supraphysiological melatonin concentrations did not decrease the midcycle LH secretion in four women studied. PMID- 2209883 TI - Serum levels of anticardiolipin antibodies are pathologically increased after active immunization of patients with recurrent spontaneous abortion. AB - Although the pathophysiological mechanisms leading to recurrent spontaneous abortion are still not fully understood, treatment schemes based on immunological principles have been advocated in recent years claiming that the production of the so-called blocking factor is being specifically stimulated. We investigated, retrospectively, whether active immunization can affect the production of immunoglobulin (Ig)G and IgM anticardiolipin antibodies. In a group of untreated recurrent spontaneous abortion patients (n = 9), the range of variation of cardiolipin antibodies, during consecutive controls taken at the same time interval as after immunization, was not statistically significant. In contrast to this, significant increases of both IgG and IgM antibodies occurred after active immunization with paternal leucocytes in 10 of 15, and in 6 of 15 cases, respectively. The mean basal and posttransfusion levels were: 7.26 +/- 2.53 and 30.15 +/- 23 U/mL for IgG and 2.26 +/- 1.2 and 6.82 +/- 5.6 U/mL for IgM, respectively. We conclude that active immunization with human lymphocytes leads to the production of antibodies against cardiolipin. This effect is exerted on both IgM and IgG antibodies. PMID- 2209884 TI - Growth patterns of nondominant ovarian follicles during the normal menstrual cycle. AB - Transvaginal ultrasound examinations were performed in seven normally cycling women to characterize growth of nondominant follicles in both ovaries. Mean follicle number showed little variation throughout the menstrual cycle with no differences between dominant and nondominant ovaries. Up to 11 follicles (greater than or equal to 2 mm) were observed in any one ovary. From observations of the first appearance of the dominant follicle (mean size 9.9 +/- 3.0 [SD] mm), selection was assumed to take place on cycle day 6.3 +/- 2.3. The diameter of nondominant follicles always remained less than 11 mm. Growth of small follicles was established in both dominant and nondominant ovaries up to the time of selection. The late follicular and luteal phases were characterized by a decrease in mean growth slopes of nondominant follicles in the dominant ovary only. These observations may provide in vivo evidence for the concept of intraovarian paracrine mechanisms and may have implications for the sonographic diagnosis of anovulation and monitoring of ovulation induction. PMID- 2209885 TI - A serial section study of visually normal pelvic peritoneum in patients with endometriosis. AB - Defined criteria were used to select small samples of visually normal study peritoneum for serial section light microscopy in 45 patients with biopsy-proven endometriosis and 10 patients without endometriosis. A glandular element compatible with possible endometriosis was found in only 1 patient. Visually normal peritoneum does not harbor a high prevalence of invisible microscopic endometriosis. PMID- 2209886 TI - The use of gonadotropin-releasing hormone agonist to regulate oocyte retrieval time. AB - We investigated the use of a gonadotropin-releasing hormone agonist (GnRH-a) to assist in the synchronous entry of a fixed number of subjects into in vitro fertilization (IVF) and gamete intrafallopian tube transfer cycle. Using a protocol in which a GnRH-a was given in the follicular or luteal phase, the clinical pregnancy rate per procedure was 27%. We conclude that the use of a GnRH a for synchronous cycles in IVF-embryo transfer is efficacious and results in acceptable pregnancy rates. PMID- 2209887 TI - Consequences of high ovarian response to gonadotropins: a cytogenetic analysis of unfertilized human oocytes. AB - Several reports have shown decreased fertilization and implantation rates in high responder patients to gonadotropins. In this cytogenetic study of unfertilized human oocytes, we have investigated possible reasons for this clinical evidence. Three groups of patients were established according to the number of oocytes retrieved: group 1 (n = 21), 1 to 5 oocytes; group 2 (n = 32), 6 to 10 oocytes; and group 3 (n = 35), greater than or equal to 11 oocytes. Patients in group 3 had lower estradiol levels per follicle developed, lower follicular volume, higher incidence of diploid oocytes, and higher rate of oocytes with an additional set of prematurely condensed sperm chromosomes of the presynthetic gap than groups 1 and 2. These results suggest that women with greater than or equal to 11 oocytes retrieved have a relative higher cytoplasmic immaturity that could explain the lower fertilization and implantation rates found in other studies. PMID- 2209888 TI - Clinical evaluation of three approaches to micromanipulation-assisted fertilization. AB - Three different micromanipulation procedures were used to assist human fertilization in cases of severe male factor infertility. Zona drilling was performed either with acid Tyrode's solution, mechanically following zona softening with chymotrypsin, or by partial zona dissection. The fertilization rate was lowest in the zona drilling/acid Tyrode's group (7/40; 17.5%), although no differences between groups (zona drilling/chymotrypsin: 21/84, 25%; partial zona dissection: 31/143, 21.7%) were significant. The fertilization rate was significantly increased relative to untreated eggs from the same patients only in the partial zona dissection group (31/143, 21.7% versus 4/102, 3.9%). Oocyte damage occurred at a high rate as a result of zona drilling with acid Tyrode's solution (13/41, 37%). Embryonic development was compromised after zona drilling with chymotrypsin: only 7/12 (58.3%) of the fertilized oocytes cleaved, and the morphology of many of the cleaved embryos was abnormal. Although only 61% (16/26) of the diploid embryos resulting from partial zona dissection cleaved, the embryonic morphology of these embryos was comparable with controls. No pregnancies resulted from the transfer of manipulated embryos. We conclude that although zona manipulation increases the fertilization rate, losses due to oocyte trauma, low rates of diploid fertilization, low rates of cleavage, and a high frequency of abnormal cleavage reduce the number of embryos available for transfer. PMID- 2209889 TI - Dummy embryo transfer: a technique that minimizes the problems of embryo transfer and improves the pregnancy rate in human in vitro fertilization. AB - Three hundred thirty-five patients selected for in vitro fertilization (IVF) were randomly divided into two groups. Group A (n = 167) was subjected to dummy embryo transfer (ET) before the start of IVF treatment to choose the most suitable catheter for each patient. Group B (n = 168) started their IVF treatment without dummy ET. Embryo transfer technique was difficult in 50 cases (29.8%) in group B, whereas no difficulty was met in group A. Pregnancy rate and implantation rate (22.8%, 7.2%) in group A were significantly higher than in group B (13.1%, 4.3%). The lower pregnancy rate in group B is due to the very low pregnancy rate (4%) in difficult ET cases. Dummy ET is a simple procedure that determines the most suitable ET catheter for each patient and avoids unexpected difficult and failed ET. PMID- 2209890 TI - Different implantation rates after transfers of cryopreserved embryos originating from donated oocytes or from regular in vitro fertilization. AB - Most oocyte donation programs have experienced higher pregnancy rates than usually seen in regular in vitro fertilization (IVF), suggesting that the quality of either the oocytes or the endometrium is superior. To clarify this issue we analyzed the results of transfers of 136 cryopreserved embryos originating either from donated oocytes (18 transfers) or from regular IVF (118 transfers). Transfers of embryos originating from donated oocytes took place after administrating oral estradiol (E2) valerate and vaginal micronized progesterone (P) following a regimen designed to mimic the serum levels of E2 and P observed during the menstrual cycle. Transfers of embryos originating from regular IVF took place either in the natural cycle (53 transfers) or after suppressing ovarian function with a single injection of a gonadotropin-releasing hormone agonist (GnRH-a), Decapeptyl-Retard 3.75 mg, and administering the same hormone replacement regimen (E2/P) used in oocyte donation (65 transfers). Eighteen transfers involving 24 embryos originating from donated oocytes were affected, resulting in six pregnancies (4 ongoing). The ongoing pregnancy rate per transfer was 22%. Seventy-nine embryos originating from regular IVF were transferred (53 transfers) in the natural cycle resulting in six pregnancies (2 ongoing). One hundred three other embryos originating from regular IVF were transferred (65 transfers) after administration of GnRH-a and E2/P resulting in four pregnancies. The pregnancy rate after transfers of embryos originating from regular IVF was 9% per transfer. This was significantly less than the pregnancy rate of 33% per transfer seen after the transfers of embryos originating from donated oocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2209892 TI - A portable digital data recorder for long-term monitoring of scrotal temperatures. AB - The application of a new, miniaturized portable digital data recorder "Thermoport" (Institute for Reproductive Medicine, Munster, West Germany) for continuous determination of scrotal temperatures revealed great variations of scrotal temperature during 24 hours in normal men. Maximum temperatures approached body core temperatures. Mean scrotal temperatures of 10 normal men rose during sauna from 32.72 +/- 0.23 degrees C to 37.53 +/- 0.38 degrees C. During treadmill running, scrotal temperatures increased by more than 2.5 degrees C. Minimal scrotal temperatures were increased in some men with varicocele compared with normal fertile men indicating impaired cooling mechanisms. The continuous temperature measurements facilitate assessment of temperature dynamics. The miniaturized design of the Thermoport makes it suitable for routine use in outpatients of infertility clinics, in occupational medicine for evaluation of heat hazards, and for investigations of body temperatures under various experimental conditions. PMID- 2209891 TI - Treatment of idiopathic testicular failure with high-dose testosterone undecanoate: a double-blind pilot study. AB - The effect of high-dose (240 mg/d) intake of testosterone (T) undecanoate was studied for sperm characteristics, function of the accessory sex glands, and hormonal parameters of men with idiopathic oligozoospermia, asthenozoospermia, or teratozoospermia using a two-phase protocol including a 3-month double-blind period followed by a 3-month open phase. Increased sperm viability and semen content of adenosine triphosphate were either not reproducible after patients on placebo were switched over to T undecanoate or did not reach statistical significance, whereas no changes were detected in other sperm characteristics and the accessory sex glands. Intake of T undecanoate significantly increased the concentration of 5-alpha-dihydrotestosterone (DHT) and the ratio of DHT over T in peripheral blood, suppressed the luteinizing hormone concentration, and tended to decrease serum follicle-stimulating hormone concentration. It is concluded that high-dose T undecanoate is not effective in the treatment of men with infertility with idiopathic testicular failure. PMID- 2209893 TI - Analysis of sperm function in globozoospermia: implications for the mechanism of sperm-zona interaction. AB - The globozoospermic condition has provided a unique opportunity to determine how the abnormal mitochondrial organization and acrosomal loss associated with this syndrome, influence sperm function. Despite the abnormal midpiece architecture, the movement characteristics of the spermatozoa, in terms of the curvilinear, path, and progressive velocities, amplitude of head displacement, and hyperactivation were all within the normal range. Similarly, the behavior of the spermatozoa on Percoll gradients was normal, although the capacity of the isolated fractions to generate reactive oxygen species was negligible. Of particular significance was the fact that the globozoospermic spermatozoa were incapable of sperm-oocyte fusion or binding the human zona pellucida, even after an intracellular calcium signal had been generated with the ionophore A23187. The sudden induction of sperm-zona interaction could, however, be achieved by the use of a ferrous ion promoter system to induce limited lipoperoxidation. This result demonstrates that the enhancing effect of peroxidation on sperm-zona adhesion involves a direct action on the properties of the sperm-plasma membrane, rather than an indirect consequence of acrosomal damage and acrosin leakage. Such findings emphasize the value of specific teratozoospermic conditions, such as globozoospermia, in dissecting the mechanisms that regulate human sperm function. PMID- 2209894 TI - Human follicular fluid stimulates hyperactivated motility in human sperm. AB - Since human follicular fluid (FF) is known to enhance the acrosome reaction and capacitation, we investigated whether hyperactivated motility is stimulated by FF. Follicular fluid-treated sperm exhibited a threefold increase in hyperactivation compared with the controls. The use of fetal cord serum in the medium, instead of bovine serum albumin, supported the same high levels of hyperactivation, although the peak occurred at 3 hours rather than 5 hours of capacitation. When sperm were treated with a steroid-rich fraction of the FF, hyperactivation was stimulated to the same degree as with whole FF. In contrast, no stimulation occurred when sperm were treated with a FF fraction stripped of steroids. The FF enhancement of hyperactivation in vitro could augment the fertilizing capacity of subfertile sperm samples, providing also a glimpse of possible in vivo events as sperm traverse the FF-laden cumulus oophorus. PMID- 2209895 TI - Genitourinary mycobacteria in infertile Egyptian men. AB - Forty infertile patients with a preliminary diagnosis of genitourinary tuberculosis were selected for our study when they presented with one or more of the following: (1) personal or family history of tuberculosis, (2) sterile pyuria, (3) voiding urinary symptoms, (4) abnormality in the epididymis, (5) hemospermia, and (6) clinically unexplained obligoathenospermia. Direct smear examination by Ziehl-Neelsen stain for 24-hour urine and freshly ejaculated semen for 3 days as well as culture of midstream urine and semen were done on egg media. Urine smear was positive (+)ive in 20 patients (50%), culture was (+)ive in 23 (57.5%), whereas for semen smear was (+)ive in 3 (7.3%) and culture was (+)ive in 5 (20%). Tuberculous mycobacteria were detected in 5 of 23 cases (21.7%). Nontuberculous mycobacteria were detected in 18 of 23 cases (78.3%). Mycobacterium smegmatis was the most common mycobacterium isolated. There was improvement of the seminal picture, though not significant, after therapy. PMID- 2209896 TI - Heterologous transplantation of activated murine peritoneal macrophages inhibits gamete interaction in vivo: a paradigm for endometriosis-associated subfertility. AB - Macrophage hyperactivation has been postulated to be the pathologic aberration in patients suffering from endometriosis-associated subfertility. In this report an in vivo model for macrophage-mediated infertility is described. Populations of macrophages were obtained from an inbred strain of mice (Balb/C) as follows: (1) in vivo hyperactivated macrophages (harvested from donor mice treated with intraperitoneal thioglycolate); (2) hyperactivated macrophages deactivated ex vivo with the protein synthesis inhibitor emetine; and (3) basal state (nonactivated) macrophages obtained from untreated mice. Recipient mice underwent ovarian hyperstimulation with pregnant mare serum gonadotropins; 2 x 10(6) macrophages were transferred on the afternoon of stimulation day 3 before injection of human chorionic gonadotropin (hCG) and mating. Unfertilized oocytes and 4-cell embryos were counted on day hCG +2 as a reflection of reproductive performance. Heterologous transfer of in vivo hyperactivated macrophages, but not basal state macrophages, significantly inhibited fertilization. This effect was largely reversed by pretreatment with emetine. These experiments confirm the relevance of macrophage-mediated interference with early reproductive performance and provide a model for the development of alternative therapies (e.g., immunomodulation of the peritoneal fluid environment) for endometriosis associated subfertility. PMID- 2209897 TI - Successful pregnancies resulting from the use of prolonged-incubation human spermatozoa in gamete intrafallopian transfer. AB - Human spermatozoa that were incubated overnight at room temperature before intrafallopian transfer with freshly collected oocytes gave rise to successful pregnancies and normal live births. The resulting pregnancy rate per transfer of 50% (4 of 8) compared favorably with the average pregnancy rate of 41.8% (38 of 91), achieved by our standard spermatozoal preparation procedure that prepared the spermatozoa approximately 2 hours before the GIFT operation. This new approach for the preparation of human spermatozoa would be applicable to oligospermic patients and some GIFT patients whose partners may have difficulties in producing a semen specimen immediately before the GIFT operation. PMID- 2209898 TI - The use of two-component fibrin sealant for embryo transfer. AB - This is a report of our preliminary experience using fibrin sealant with a series of 38 patients undergoing IVF and ET. We used a two-component fibrin sealant to create a fibrin plug in the uterine cavity at the time of ET to decrease the possibility of embryo expulsion and also ectopic pregnancy. Our preliminary report proves that it is possible to obtain 26% pregnancies using this two component biological glue instead of serum or culture medium for uterine embryo replacement. A prospective randomized study will be undertaken to evaluate whether the use of fibrin sealant could significantly improve IVF and ET results. PMID- 2209899 TI - Pregnancy after in vitro fertilization in a patient with stage I endometrial carcinoma treated with progestins. AB - A 35-year-old woman with chronic anovulation and bilateral tubal disease was found during infertility evaluation to have grade I endometrial carcinoma confined to an endometrial polyp. She was treated with polypectomy and endometrial curettage followed by high-dose progestagens for 6 months. Endometrial curettage at 3 and 6 months of therapy indicated regression of the lesion and the patient subsequently achieved successful pregnancy with IVF. PMID- 2209900 TI - Secondary hypogonadism in hemochromatosis. AB - Hemochromatosis is a rare disorder of iron storage. This report illustrates a case of hypogonadotropic-hypogonadism in a female with biopsy-proven hemochromatosis. Dynamic pituitary and gonadal testing revealed subnormal gonadotropin responses to gonadotropin-releasing hormone (GnRH) but normal ovarian reserve, as shown by normal follicular stimulation with hMG. Thus, abnormalities of ovulation and menstruation in patients with hemochromatosis are most likely because of inadequate pituitary responsiveness to GnRH. PMID- 2209901 TI - Semen donor insemination. PMID- 2209903 TI - Leber's hereditary optic neuropathy. PMID- 2209902 TI - Testing for sperm and ovarian antibodies? PMID- 2209904 TI - The corneal endothelium. AB - The endothelium is a monolayer of cells on the posterior corneal surface that transports water from the stroma into the anterior chamber. This movement of water counters a natural tendency for the stroma to swell and is necessary to maintain a transparent cornea. Embryologic studies, in particular the demonstration of the derivation of the endothelium from the neural crest, have provided insight into the factors that govern the response of this tissue to disease. In some species the endothelium can regenerate after injury, but in man cellular enlargement is the main mechanism of repair after cell loss. A clinical estimate of endothelial cell density and function is provided by specular microscopy, fluorophotometry and pachymetry. In this paper we review the development, structure and function of the corneal endothelium, and then consider the pathological processes that can affect this tissue. PMID- 2209905 TI - The complications of trabeculectomy (a 20-year follow-up). AB - The complications of trabeculectomy were studied in two groups of patients taken from a stable white population. The first group who had had their operation when it was first introduced 22 years ago, had been previously treated with prolonged medication, the second group had been operated upon recently and had had short term pre-operative medication. This study confirmed that trabeculectomy predictably reduces the intraocular pressure to within the accepted normal range and that the pressure level below which the intraocular pressure could not be expected to fall was congruent to 14 mm/Hg. It also revealed that although some post operative abnormality was noted in two-thirds of the patients there were no long term problems which could be related to any operative or immediately post operative complications, including shallow anterior chambers, uveitis and hyphaema. However, there was a long term reduction in the visual acuity and visual fields of about one-third of the patients, which was not related to cataract formation, macular problems, the height of the preoperative intraocular pressure, the amount by which this fell as a result of the surgery, or the amount, length or type of preoperative medication given before the operation. Although there was some increase in cataracts throughout the whole long term group this was mainly in those who had cataract prior to surgery; the increase was not related to operations or any other factor other than corneo-lenticular contact post-operatively. PMID- 2209906 TI - Mechanisms leading to an acute rise in intraocular pressure in retinal vein occlusion. AB - Forty patients with retinal vein occlusion were studied to investigate possible mechanisms leading to an acute rise in intraocular pressure. A rise in intraocular pressure on recumbency was found in 64% of eyes with a central retinal vein occlusion and 65% of eyes with a branch retinal vein occlusion. This finding correlated with glucose tolerance test score, and may be the result of abnormal glucose tolerance in these patients. Following provocative testing using pilocarpine and phenylephrine, no eye showed irido-corneal contact or angle closure, however over 50% of eyes release pigment into the anterior chamber. Fifty-two per cent of central retinal vein occlusion and 71% of branch retinal vein occlusion eyes that released pigment showed a rise in intraocular pressure. PMID- 2209907 TI - Peribulbar versus retrobulbar anaesthesia. AB - A prospective clinical trial comparing peribulbar with retrobulbar anaesthesia is reported. Ninety-nine consecutive patients for cataract extraction under local anaesthesia were randomly allocated to a peribulbar or retrobulbar technique. The effectiveness of the anaesthetic, the operative conditions, and the degree of patient discomfort were recorded. Pain scores (as assessed separately by the patient, surgeon, and attendant nurse) demonstrated that anaesthetic administration and surgery were less painful with the peribulbar method. This technique gave more reliable ocular akinesia and orbicularis oculi paralysis in addition to a lower operative complication rate. PMID- 2209908 TI - Secondary evaluation of hydrogel lens implants. AB - OBJECTIVE: To review patients currently forming part of a study of poly 2 hydroxyethylmethacrylate (P-HEMA) 'Hydrogel' intraocular lenses. DESIGN: Patients were taking part in the Hydrogel arm of a prospective trial at Scarborough Hospital. Recruitment was by letter. SETTING: District General Hospital. PATIENTS: One hundred and eight from the Scarborough trial in whom a Hydrogel lens had been implanted. INTERVENTIONS: An independent assessment was carried out at a median interval of 20 months following surgery. Visual acuities were assessed with best possible refraction and the eyes examined both before and after pupil dilation. MAIN OUTCOME MEASURES: Visual acuity and major complications. RESULTS: 91% had visual acuities of 6/9 or better and 30% achieved 6/5. In 61% the central area (3 mm diameter) of posterior capsule was clear but 39% had significant fibrosis or pearl formation in this area and 8% had undergone posterior capsulotomy. Five major decentrations had taken place, one of which occurred following a spontaneous rupture of the posterior capsule 17.6% of patients showed significant pigment dispersion behind the IOL either on the posterior capsule or in the anterior vitreous that could not be accounted for purely by surgical trauma. An atonic iris sphincter was noted in 17% of eyes. CONCLUSIONS: This lens gives good visual results but its stability and tendency to cause pigment shedding need to be closely monitored. PMID- 2209910 TI - The investigation of patients with retinal vascular occlusion. AB - The investigation of patients with retinal artery occlusion, retinal vein occlusion and cotton wool spots is discussed. The majority are due to either emboli or atheroma and occur in elderly patients. A full clinical history and examination remain the essential part of the investigation but the ophthalmologist must select patients in whom further investigation is warranted. The recent recognition of the importance of antiphospholipid antibodies and natural anticoagulant deficiency states in the pathogenesis of thrombosis has identified a group of young people in whom specific therapy may be indicated. PMID- 2209909 TI - The Mersilene mesh ptosis sling. AB - A variety of materials are currently available for use in brow suspension ptosis surgery when an alternative to autogenous fascia lata is indicated. We describe the use of a Mersilene mesh sling, developed to overcome the problems of failure and extrusion commonly associated with substitute suspensory materials. The results and follow up in 23 cases of blepharoptosis are presented. Our findings suggest that the Mersilene mesh sling has a definite place in ptosis management; we currently use this sling for all cases in which autogenous fascia lata is considered inappropriate. PMID- 2209911 TI - Subretinal gas. AB - Two cases of subretinal gas are described. The circumstances in which this complication arose are important in understanding the mechanism by which gas gains access into the subretinal space. Evacuation of subretinal gas by posturing should be avoided as this leads to an increase in the extent of the retinal detachment and its extension anterior to involve the nonpigment epithelium of the pars plana. A technique for removing subretinal bubbles of expanding gases using vitrectomy and fluid/gas exchange is recommended. PMID- 2209912 TI - Ocular autonomic nerve function in Lambert-Eaton myasthenic syndrome. AB - Autonomic innervation to the eye and ocular adnexae was assessed in seven patients with Lambert-Eaton Myasthenic Syndrome and 50 age-matched control subjects. Pupil responses to light were abnormal in 69% of LEMS patients, compared with 18% of the control group. Reflex tear production--a screening test for parasympathetic innervation to the lacrimal gland--was below the accepted normal limit in 69% of LEMS patients. Parasympathetic and sympathetic denervation hypersensitivity of the iris musculature were individually present in 57% of LEMS patients, compared with 6% of control subjects. The association between autonomic dysfunction and Lambert-Eaton Myasthenic Syndrome is discussed. PMID- 2209913 TI - Leber's hereditary optic neuropathy in women. AB - Four women, from three families, are presented who developed severe bilateral optic nerve disease. A diagnosis of Leber's hereditary optic neuropathy (LHON) was made when male family members became affected. The disease ran a similar course in men and women with severe and permanent reduction in vision. Two women had been told that they suffered from multiple sclerosis. With recent advances in diagnostic techniques it should be possible to distinguish between these two conditions. Although LHON may be underdiagnosed in women, there does seem to be a male preponderance of the disease in most European pedigrees. Recent work supports the assumption that LHON is transmitted via cytoplasmic DNA; however, this does not explain why men are more likely to be affected, nor why only a minority of those carrying the defect develop the disease. PMID- 2209914 TI - Intraocular tuberculosis. AB - Twelve patients with a diagnosis of intraocular tuberculosis are described. Nine patients presented with florid ischaemic retinal vasculitis and a marked tendency to neovascularisation. Two patients developed choroidal tubercles; iris nodules were observed in association with anterior uveitis in the remaining patient. The methods of diagnosis, management and possible mechanisms of pathogenesis of these different clinical presentations are discussed. PMID- 2209915 TI - Predictors for likelihood of corneal transplantation in keratoconus. AB - A group of 70 patients who had attended the Keratoconus Clinic at Moorfields Eye Hospital over a 10-year period were analysed retrospectively. At the end of this period 23 eyes had undergone corneal transplantation. This gave an overall probability of 16%, various information obtained at the initial visit was then analysed for a possible relationship with the probability of needing a transplant within ten years. The only significant relationship found was the initial corneal radius as determined by the back optic radius of the first contact lens. A graph was constructed plotting probability of corneal transplant against each radius at the first visit, which could assist clinicians in advising patients. PMID- 2209916 TI - Ocular enlargement following infantile corneal opacification. AB - Congenital hereditary endothelial dystrophy (CHED) is not generally thought to be associated with other ocular abnormalities. Ultrasonography in a series of twenty eyes (ten patients) with CHED shows ocular enlargement similar to that occurring in uncomplicated axial myopia. There was an inverse relationship between the degree of enlargement and the visual acuity or visual result following penetrating keratoplasty suggesting that infantile corneal oedema sufficient to cause stimulus deprivation may result in abnormal enlargement of the globe. PMID- 2209917 TI - Dominant inherited tilted disc syndrome and lacquer cracks. AB - Three patients with the tilted disc syndrome from one family were examined. The presence of the trait in three consecutive generations suggests an autosomal dominant mode of inheritance, although in these patients with variable expression. The propositus showed bilateral inferonasal retinal ectasia, with atrophic subretinal scars. Linear-like lacquer cracks, radiating from the central scars, were also present running parallel to the margin of the optic nerve head. The linear streaks were very similar to those usually seen in traumatic tears of Bruch's membrane. The mechanical stretching of the ectatic area, and its abnormal location inferonasal to the optic disc might have been responsible for the unusual pattern of the lacquer cracks in our patient. PMID- 2209918 TI - Per-nasal swabbing as an aid to the diagnosis of chlamydial and adenovirus conjunctivitis. AB - Two hundred and thirty four patients (adults and babies) with conjunctivitis were investigated by taking eye swabs and in addition by taking per-nasal swabs. Chlamydia trachomatis was isolated from 20 patients and adenovirus from 14 patients. Per-nasal swabbing led to a 53% increase in chlamydia diagnosis and a 27% increase in the diagnosis of adenovirus infection. It is suggested that per nasal swabbing has an important role to play in detecting chlamydial conjunctivitis which itself may be an indicator for high morbidity in patients and their contacts. PMID- 2209919 TI - Combination low dose cyclosporin A and steroid therapy in chronic intraocular inflammation. AB - Thirteen patients with chronic intraocular inflammation which had not been adequately controlled with oral prednisolone entered into an open study of low dose Cyclosporin A (mean 4.1 mg/kg/day) combined when required with oral prednisolone (15 mg prednisolone per day or less). The mean duration of treatment was 26 months (range 8-44) over a mean follow-up period of 29 months (range 8 49). Visual acuity improved overall in ten patients, and remained stable in three. Six patients have completed a course of Cyclosporin A therapy, and four of these patients have retained their visual improvement. Two have returned to the pretreatment level of vision. Only one patient has required conversion to alternative immunosuppressive therapy. The mean serum creatinine concentration had increased significantly by 26% after six months (p less than 0.05) and 32% after one year (p less than 0.01) but remained stable during the subsequent 18 months. Four patients developed hypertension requiring hypotensive therapy. On cessation of CsA treatment, the mean serum creatinine concentration fell to the upper reference limit. The elevation of serum creatinine concentration was significantly higher in patients who either developed hypertension during Cyclosporin A therapy or who were previously known to be hypertensive. Patients with nephrotoxicity were significantly older than those in whom serum creatinine concentration remained within the reference range. Lithium clearance studies showed evidence of proximal renal tubular dysfunction which was partially reversible on dose reduction or withdrawal. PMID- 2209920 TI - Topical flurbiprofen: an effective treatment for episcleritis? AB - Topical flurbiprofen was compared with placebo and prednisolone 0.3% in the treatment of episcleritis by a randomised double-blind trial. Seventy-seven eyes were included in the trial. Rapid spontaneous improvement in symptoms and signs was noted in the majority of cases. There was no significant difference between the cure-rates of patients treated with flurbiprofen and placebo over a 3-week trial period. The proportion of patients treated with prednisolone 0.3% who were cured was significantly higher than in either of the other groups after 3 weeks. PMID- 2209921 TI - Penetration of synthetic corticosteroids into human aqueous humour. AB - The penetration of prednisolone acetate (1%) and fluorometholone alcohol (0.1%) into human aqueous humour following topical application was determined using the very sensitive and specific technique of Gas Chromatography with Mass Spectrometry (GCMS). Prednisolone acetate afforded peak mean concentrations of 669.9 ng/ml within two hours and levels of 28.6 ng/ml in aqueous humour were detected almost 24 hours post application. The peak aqueous humour level of fluorometholone was 5.1 ng/ml. The results are compared and contrasted with the absorption of dexamethasone alcohol (0.1%), betamethasone sodium phosphate (0.1%) and prednisolone sodium phosphate (0.5%) into human aqueous humour. PMID- 2209922 TI - [Changes in TSH-receptor antibody (TR-AB) and thyroid stimulating antibody (TS AB) after thyroidectomy in thyrotoxic patients]. AB - Changes in TSH-receptor antibody (TR-Ab) and thyroid stimulating antibody (TS-Ab) after thyroidectomy were examined in seventeen thyrotoxic patients (3 males and 14 females, 40.0 +/- 3.4 yr) with positive TR-Ab and TS-Ab. They were subjected to thyroid surgery because of suspected malignancy, methymazol induced agranulocytosis, cardiac failure, recurrent gastric ulcer or emotional instability. Of these patients, 3 were totally thyroidectomized, 11 were subtotally thyroidectomized and 3 were unilaterally lobectomized. Histological findings in these patients showed diffuse hyperplasia in 8 cases, an adenomatous goiter in 3, diffuse hyperplasia plus follicular adenomas in 5, and Hashitoxicosis in one. Their thyroid function before surgery was as follows: T3 level, 3.9 +/- 0.7 ng/ml; T4, 19.5 +/- 3.3 micrograms/dl; free T3, 11.9 +/- 1.2 pg/ml; free T4, 4.9 +/- 1.0 ng/dl; and TSH, 0.9 +/- 0.1 microU/ml. Mean levels of TR-Ab and TS-Ab before surgery were 56.8 +/- 4.6% and 1,218.6 +/- 262.4%, respectively. Positive anti-thyroid antibody (TGHA) was 47.0%, positive anti microsomal antibody (MCHA) was 88.2% in these thyrotoxic patients, and mean levels of TGHA and MCHA were 1,688 +/- 715 and 89,280 +/- 34,717 times, respectively. After the operation, these parameters were decreased and their thyroid functions became an euthyroid or a hypothyroid state one month later. The incidence of post-operative hypothyroidism was 45.5% in subtotally thyroidectomized patients, 33.3% in unilaterally lobectomized patients and 100% in totally thyroidectomized patients. TR-Ab levels decreased from 56.2 +/- 6.5% before surgery to 24.5 +/- 12.2% 12 months after surgery, but increased again to 35.0 +/- 15.7% 24 months after surgery in subtotally thyroidectomized patients. These levels also decreased from 50.4 +/- 11.0% before surgery to 37.8 +/- 11.4% 12 months after surgery, and remained unchanged to 38.2 +/- 10.4% 24 months after surgery in unilaterally lobectomized patients. On the other hand, in totally thyroidectomized patients, TR-Ab levels decreased and normalized 12 months after surgery. One of subtotally thyroidectomized or unilaterally lobectomized patients developed recurrent thyrotoxicosis with an increased positive TR-Ab. Mean levels of TS-Ab decreased to 28.3 +/- 181.3% and 152.5 +/- 47.9% 12 and 24 months after surgery, respectively, in subtotally thyroidectomized patients. These levels decreased 12 months after surgery and then increased again to 303.6 +/- 130.6% in unilaterally lobectomized patients. On the other hand, TS-Ab levels decreased and normalized to 94.3 +/- 3.9% 6 months after surgery in totally thyroidectomized patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2209924 TI - [The effect of epidermal growth factor (EGF) with estradiol and progesterone on prolactin secretion from cultured human decidual tissues of early pregnancy]. AB - Prolactin is now accepted as a normal product of the decidual cells of the human endometrium. We investigated the effect of epidermal growth factor (EGF) with estradiol and progesterone on prolactin secretion by the decidual tissues from the early pregnant endometrium. The decidual tissues were separated from villi, minced and cultured in collagen gel matrix with serum-free medium. Immunological staining of the cultured decidual tissues showed prolactin localization and EGF receptors on the stromal cells. Cultured media were collected every 2 days. The culture for the first 2 days was incubated with the serum-free medium alone (= preculture), and the following test culture was supplemented with/without additives. The prolactin content in cultured media was quantified by EIA. The results of the effect of steroid(s) and EGF were represented as a comparison of prolactin contents in the preculture and the test culture. An increase in prolactin secretion was found after the tissues were treated with a combination of 10(-8)M estradiol and 10(-6)M progesterone or 10(-6)M progesterone alone. After 8 days, the prolactin secretion rate increased about 3-fold over the precultured value. Estradiol alone kept the prolactin secretion at the precultured value. Prolactin secretion gradually decreased in the non-additive culture. These results indicate that progesterone was essential in the secretion of prolactin. Simultaneously, similar decidual tissues were incubated with a combination of EGF and steroid(s). The secretion of prolactin in the group treated with progesterone alone decreased dose-dependently responding to added EGF on the 8th day of culture. In the presence of estradiol and progesterone, the secretion rate decreased to the values similar to the progesterone alone group with the addition of 0.1, 1 ng/ml EGF, and the decrease in prolactin secretion was less with the addition of 10 ng/ml EGF. Mixed cultures of the decidual tissues and villi showed that the prolactin secretion rate increased in all groups treated with/without estradiol and/or progesterone. These results imply that progesterone derived from villi might control decidual prolactin secretion. The effect of high concentration EGF (50 ng/ml) on the prolactin secretion appeared similar to the isolated decidual tissues. These results suggest that decidual prolactin secretion is regulated by the combined effects of steroids and EGF. PMID- 2209923 TI - [Radioimmunoassay for dexamethasone and its plasma levels after oral administration in patients with liver disease]. AB - Dexamethasone (DXM), one of the strong synthetic glucocorticoids, has been used widely for therapeutic purposes and for evaluation of the hypothalamic-pituitary adrenal axis. However, information concerning the plasma concentrations of DXM and its metabolism in various liver diseases is limited. In this study, plasma DXM levels were examined in patients with chronic inactive hepatitis (CH), patients with liver cirrhosis (LC) and normal subjects (NR) after oral administration of one milligram DXM. Plasma DXM levels were measured directly in plasma extract, using reliable and sensitive radioimmunoassay (RIA). The antiserum was obtained by immunizing rabbits with DXM-3-oxime-bovine serum albumin conjugate. Standard curves for DXM were obtained over the range 10-5000 pg. The cross reactivity of endogenous steroids with DXM antiserum was less than 0.1%. In the group of NR, the peak of plasma DXM was 20.9 +/- 2.9 ng/ml within 1.3 +/- 0.4 hours after administration. Half time of its disappearance was 3.3 +/ 1.1 hours, and plasma DXM disappeared in 24 hours, remaining less than 1 ng/ml. In patients with CH and those with LC, the peak levels of DXM were 10.8 +/- 1.0 ng/ml and 10.5 +/- 0.5 ng/ml, respectively, and those values were significantly lower than those of NR. Half time of DXM disappearance in patients with CH and in those with LC were 6.2 +/- 0.6 and 6.3 +/- 0.6 hours, respectively, significantly prolonged compared with that of NR. Although DXM metabolism was impaired in CH as well as in LC, the retention rate of indocyanine green (ICG) at 15 minutes in CH was found within the normal range, 10.0 +/- 1.1%, respectively. These results might suggest that the impaired DXM metabolism in patients with chronic liver disease may be affected not only by the decreased hepatic blood flow but also by some other factors. PMID- 2209925 TI - [63rd fall meeting of the Japan Endocrine Society. Gifu City, 1-2 November 1990. Abstracts]. PMID- 2209926 TI - Status of Plasmodium falciparum resistance to chloroquine in Gujarat, Rajasthan and Maharashtra states of India. AB - An extended study from 1978-88 revealed that in the western states of India i.e., Rajasthan, Gujarat and Maharashtra; P. falciparum resistance to chloroquine has a scattered pattern in its distribution. However in Gujarat, R-III level of resistance is established in southern districts showing four fold increase from 1.79% in 1985 to 8.2% in 1988. In this area use of some alternate drug is indicated. PMID- 2209927 TI - Active malaria transmission in South Mizoram. AB - Anopheles dirus was incriminated as malaria vector with 1.12% sporozoite rate in Tlabong (Demagiri) subdivision, Mizoram. High parity rate of A. dirus (33.69%) and A. minimus (52.87%) further confirmed their vectorial status. Both the vectors were found highly susceptible to 4% DDT. PMID- 2209928 TI - Morphological variations in some Indian anophelines from Koraput district, Orissa, India. PMID- 2209929 TI - Evaluation of certain mosquito repellents marketed in India. AB - A study was carried out in certain villages of Distt. Ghaziabad (U.P.) to evaluate the efficacy of commercially available mosquito repellent preparations and devices. Results revealed that none of the repellents tested provided absolute protection against mosquito bites. The protection varied from 38 to 98% with different species of mosquitoes. In general, better protection was provided against Anopheles bite than against Culex. Of ten repellents evaluated. Mylol oil and Tortoise coils were marginally superior to Odomos cream and Rooster coils. Among electrical devices, Good Bye and Casper were marginally superior to Good Knight and Knight Queen. PMID- 2209930 TI - Fine structure of the erythrocytic stages of Plasmodium vivax and the host cell alterations. AB - Fine structural analysis of the trophic and sexual stages of Plasmodium vivax obtained from naturally infected humans revealed that in general, the structural features as well as certain specialized functions such as haemoglobin ingestion and utilization etc., are similar to those described for other malaria parasites. Young trophozoite is characterised by less condense cytoplasm with scattering of free ribosomes and minimum amount of endoplasmic reticulum. The trophozoite grows by feeding on the host cell cytoplasm with its cytostome. Older trophozoite gets considerably enlarged and its cytoplasm appears coarsely granular due to an increase in endoplasmic reticulum and ribosomal content. The two sexual forms, the macro- and microgametocyte, can be distinguished on the basis of their fine structure. The macrogametocyte has high ribosomal density and more osmiophilic bodies than microgametocyte and possesses a compact dense nucleus with nucleolus like region whereas the microgametocyte has large diffuse nucleus without nucleolus. Caveola-vesicle complexes and cytoplasmic clefts are observed in all erythrocytes infected with P. vivax and the incidence of these host cell alterations increases as the intraerythrocytic parasite matures. PMID- 2209931 TI - Chloroquine sensitivity of Plasmodium falciparum in Shankargarh block of Allahabad district (U.P.). AB - Chloroquine sensitivity of Plasmodium falciparum was carried out in Shankargarh block of Allahabad district, U.P. to confirm the presence of resistant strain in the area. A total of 47 cases were subjected to in vivo extended test, of which resistance was detected in 11 cases at R-II/R-III level and in 9 cases at R-I level. One case out of 18 subjected to standard 7-day in vivo test showed resistance at R-III level. Micro in vitro test was done for 24 cases, of which growth was seen in 21 control samples. Out of these 7 cases were found to be resistant. The significance of the findings are discussed. PMID- 2209932 TI - Quartan malaria--an investigation on the incidence of Plasmodium malariae in Bisra PHC, District Sundargarh, Orissa. AB - A longitudinal study on the incidence of P. malariae was taken up from September 1988 to December 1989 in Bisra block, District Sundargarh, Orissa covering 38,615 population, which is mainly tribal. The area is a known hard-core malarious region in the Garhjat hill range in eastern India. In this study, out of 22,217 blood smears examined through weekly active surveillance, 7362 (33.1%) were found malaria parasite positive. Out of the total positive cases, 82 (1.1%) were P. malariae. These occurred mostly (91.4%) in persons below 40 years of age and children below 9 years accounted for 36.6% of total quartan malaria cases. In this age group the disease was found to be associated with splenomegaly (average enlarged spleen 2.07; spleen rate 45.9%) and 9 out of 13 mixed infections of P. malariae with P. falciparum and/or P. vivax were detected from this age group. This is the first report of quartan malaria from this area. PMID- 2209933 TI - Relapse pattern of Plasmodium vivax in Kheda district, Gujarat. AB - A study on relapse pattern of P. vivax in Kheda district of Gujarat revealed that the relapse rate in P. vivax within 8 months of primary attack was around 40% in untreated cases. It was 2.6% within one year in patients treated with 5-day course of primaquine. Relapses occurred more frequently from April to October and 82% relapses occurred within one year of the primary attack. Relapses occurred up to 4 years after primary attack but they were less frequent in 3rd and 4th year. PMID- 2209934 TI - Holding a successful staff meeting. PMID- 2209935 TI - Chairside surface asepsis. PMID- 2209936 TI - Mandatory education and credentialing for dental assistants: is it the answer to the manpower crisis? AB - One reason for the nationwide shortage of dental assistants is lack of professional recognition. This lack of recognition stems from the fact that, unlike dentistry and dental hygiene, dental assisting has no nationally standardized, mandatory requirements for education and credentialing. Dentists acknowledge that the lack of professional recognition is a reason dental assistants frequently give for leaving the profession, as well as a barrier for potential assistants who might enter the profession. PMID- 2209937 TI - [Amalgam reconstruction for coronal-radicular extension]. PMID- 2209938 TI - [Focal pathology and infectious dental foci. Theoretical and clinical aspects]. AB - A relationship between bucco-dental infection and distant tissue lesions has been recognized for many years. However the pathogenesis of focal odontostomatogenous infection is still not fully understood. At the moment a special attention is paid to the auto immune pathogenesis, but, how focal infection could cause distant tissue injury remains to be investigated. The importance of prevention of infective endocarditis is underlined and prophylaxis procedures are discussed. PMID- 2209939 TI - [Action of etching acid on lining materials]. AB - A review was made of the literature concerning intermediate materials for composite resin fillings and the possibilities of ortho-phosphoric acid infiltration. An experimental study was aimed at evaluating the damages caused by the acid action of the etching material on various type of base materials used. In conclusion, various procedures are suggested for composite resin restoration in order to avoid the risks of lesions of the pulp-dentin organ. PMID- 2209940 TI - [Study of cellular kinetics in oral leukoplakia]. AB - The Authors aim was to study the Labeling Indices (LI) of 12 subjects with oral leukoplakia, using an in vitro labeling technique with tritiated thymidine (Silvestrini-Kit, Ribbon spa, Milan). Twelve volunteers of our Dental Clinic were enrolled in this study as a control group. The kinetic parameter was investigated by counting cells from autoradiographs on histological selections of the biopsies. By a Wilcoxon test, significant differences were found between the LI of the two groups: p = 0.00003. Finally, a comparison has also been made between LI of these lesions and the LI of oral squamous cell carcinomas. PMID- 2209941 TI - [Instruments for periodontal surgery. Indications for choice]. AB - The Authors, using their personal experience, discuss the necessary instruments for periodontal surgery (osseous and mucogingival), their quality and proper arrangement on the surgical table. PMID- 2209943 TI - [By simple means an optimum of esthetics]. PMID- 2209942 TI - [Subcutaneous emphysema during intraligamental anesthesia]. AB - Periodontal ligament anaesthesia (PDLA) is a good choice to most common local anaesthesia methods. In the present work the Authors report a case of subcutaneous emphysema as adverse effect of this injection technique. PMID- 2209944 TI - [Technical assistance in the planning of dentures]. PMID- 2209945 TI - [Metal-free bridges in posterior region]. PMID- 2209946 TI - [Bond strength of Rocatec systems]. PMID- 2209948 TI - [Rational modelling technic. Purposeful use of auxiliary structure]. PMID- 2209947 TI - [More certainty of quality information of gold alloys]. PMID- 2209949 TI - [State of the art 1990. Galvanoplastic prepared framework]. PMID- 2209950 TI - [PVD-coating in dental technology. Evolution and future perspectives]. PMID- 2209952 TI - [Laboratory side of preparation of ceramic facings. Durability concerns of malformed teeth]. PMID- 2209951 TI - [Inlay and onlay technic today. Modelling of cast gold inlays]. PMID- 2209953 TI - [Complete restoration. Observations of a case]. PMID- 2209954 TI - [Groove-shoulder-pin attachment. Second and third mill step]. PMID- 2209955 TI - [New knowledge of preheating process. Indications for practitioner]. PMID- 2209956 TI - [Combination prosthesis in course of time]. PMID- 2209957 TI - [Inlay and onlay technic today. Casting technic and finishing]. PMID- 2209959 TI - [Analysis of anatomic occlusal surface condition]. PMID- 2209958 TI - [Basic measure from a dispenser. Exact thickness strengths are standard]. PMID- 2209960 TI - [Systematic work procedures in waxing technic]. PMID- 2209961 TI - [Ceramic occlusal surfaces. Symbiosis out of creativity and perfection]. PMID- 2209962 TI - [New bonding systems between synthetic resins and dental alloys]. PMID- 2209963 TI - [Silaceram in cross fire. Nothing but black paint]. PMID- 2209965 TI - [Preparation of telescopic crowns of non-precious alloys]. PMID- 2209964 TI - [Defect prosthesis after total maxillary resection]. PMID- 2209966 TI - [Inlay and onlay technics today. Metal mounted ceramic inlay]. PMID- 2209967 TI - [Ceramic partial crown. An alternative in the future?]. PMID- 2209968 TI - [Nickel-chromium alloys from laboratory point of view. Ten-year clinical study]. PMID- 2209969 TI - [Finishing a combination prosthesis with extracoronal attachments]. PMID- 2209970 TI - [Third set of teeth. Harmony with nature]. PMID- 2209972 TI - [Day of the conical crown]. PMID- 2209971 TI - [Myths--facts--practice. Experience with pure titanium preparations]. PMID- 2209973 TI - [Inlay and onlay technics today. Full ceramic inlay]. PMID- 2209976 TI - [Corrosion and biocompatibility of dental alloys]. PMID- 2209975 TI - [Reinhardt's trim apparatus. Importance and preparation of occlusal models]. PMID- 2209974 TI - [Correctable "Basisbrand". Layering technic for every day]. PMID- 2209978 TI - [Not an everyday case. Concerns for a cleft palate]. PMID- 2209977 TI - [Combination and bridge technic aspects of master examination, Munich, 1989]. PMID- 2209979 TI - Better not bigger: a practice model for the 90s. PMID- 2209981 TI - Prefabricated communications for your dental office. PMID- 2209980 TI - Perio disease: target market for 90s' GPs. PMID- 2209983 TI - National survey of dentists' incomes. PMID- 2209982 TI - Dental labeling for geriatric patients. PMID- 2209984 TI - Nine tax questions frequently asked by dentists. PMID- 2209985 TI - Protocol for managing doctor-patient-doctor disputes. PMID- 2209987 TI - How to be a good witness in court. PMID- 2209988 TI - Fringe benefits: back on the front burner. PMID- 2209986 TI - Motivation: you've got it--can you keep it alive? PMID- 2209989 TI - How are you doing? Break even point analysis. PMID- 2209990 TI - Reading the financial pages for profit. PMID- 2209992 TI - Do-it-yourself investing. PMID- 2209991 TI - Narcotic analgesic combinations. PMID- 2209993 TI - Case presentations: a team approach. PMID- 2209994 TI - Freedom in dentistry: a look at the other side. PMID- 2209996 TI - Contracts for dental work. PMID- 2209997 TI - How to avoid financial scams. PMID- 2209995 TI - How much is your practice worth? PMID- 2209998 TI - Maximize your tax-exempt income. PMID- 2209999 TI - The generalist-specialist relationship. PMID- 2210000 TI - Will raising fees hurt your practice? PMID- 2210002 TI - Electrify your practice. PMID- 2210001 TI - Where is dentistry headed in the '90s? PMID- 2210003 TI - Esthetic dentistry in the next decade. PMID- 2210004 TI - Small-town practice off to good start. PMID- 2210005 TI - Evidence of neutralizing activity against T3 coliphage in oyster Crassostrea gigas hemolymph. AB - To investigate defense reactions of bivalve molluscs against viruses, experimental in vitro assays have been developed using T3 coliphage as a test virus. A native neutralizing factor in oyster Crassostrea gigas serum showed high individual variability and was enhanced significantly by repeated sampling of hemolymph from the same oysters. The responsible factor is apparently thermolabile and sensitive to EDTA treatment. Because of an inhibitory effect by the enzymatic inhibitor, phenylmethylsulphonyl fluoride (PMSF), the T3 neutralizing factor may be related to serine protease. PMID- 2210006 TI - Direct binding and lectin-mediated binding of erythrocytes to haemocytes of the insect, Extatosoma tiaratum. AB - Treatment of Extatosoma haemocytes on a monolayer with fixed rabbit erythrocytes (RE) in the presence of Ca2+ results in ca. 11% plasmatocytes (PL) and 58% spreading granular (SG) cells rosetting. Pretreatment of haemocytes with lactose, D-galactose, or asialofetuin reduces rosetting, suggesting that the membrane associated receptors involved may be lectins. The percentage of rosetting PL and SG cells is increased by a number of heterologous lectins (indicating the presence of D-galactose, mannose, and Glu Nac receptors on these haemocytes) and a D-galactose specific lectin isolated from the serum of the insect. The latter acts as a bridging molecule and requires Ca2+ to bind to specific receptors on both haemocytes and fixed RE. PMID- 2210007 TI - Phylogeny of neuroimmunoregulation: effects of adrenergic and cholinergic agents on the in vitro antibody response of the rainbow trout, Onchorynchus mykiss. AB - The ability of the nervous system to influence a variety of immune processes has been well established in mammals. There are, however, few studies on how the peripheral nervous system might affect immunity in the lower vertebrates. This study demonstrates that autonomic neurotransmitters (or their analogs) can significantly influence the in vitro induction of antibody-secreting cells in cultures of splenic leukocytes from the rainbow trout. Beta-adrenergic agonists suppress, while alpha-2 adrenergic and cholinergic agonists enhance the in vitro antibody response to the T-independent antigen TNP-LPS. These effects are receptor mediated as evidenced by the action of specific receptor antagonists. These results, taken with the previous findings that the salmonid spleen contains a rich adrenergic innervation, and that chemical sympathectomy results in an enhanced in vivo antibody response, strongly suggest that autonomic neurotransmitters may affect immune function in teleosts via leukocyte receptors for these factors. PMID- 2210009 TI - Adoptive immune responses of chicken immunocytes in embryonic and neonatal hosts. AB - The adoptive immune capacities of peripheral blood immunocytes from unprimed juvenile B haplotype-matched donors were compared in late embryonic and neonatal chick hosts. Adoptive PFC counts of immunocytes that responded to mouse erythrocytes (MER+) were high in late embryo and newly hatched chick hosts but somewhat less in older neonatal hosts. In contrast, the PFC levels of immunocytes that responded to sheep erythrocytes (SER+) were high in late embryo and older neonatal hosts, but conspicuously depressed in newly hatched chick hosts. The addition of spleen cells from neonatal 4- to 7-day chick donors to the donor cell inoculum appeared to enhance the adoptive immune responses of MER+ cells in embryonic hosts. PMID- 2210008 TI - Pathways of signal transduction in teleost nonspecific cytotoxic cells. AB - In the present study evidence is presented that both a putative "receptor" binding monoclonal antibody (mAb) and the calcium ionophore A23187, either singly or together, increase receptor expression and lysis of IM-9 target cells by catfish NCC. NCC activity against IM-9 target cells was increased 55% after 1 h mAb treatment. Receptor expression determined by flow cytometry increased 95% following 18-h treatment. A23187 treatment of NCC produced greater than 200% increases in receptor expression. Combined treatments of NCC with 10(-4) M A23187 and 10(-7) M PMA however augmented receptor expression only 22% above that produced by A23187 alone. MAb and A23187 comodulated cytotoxicity by a 65% increase over ionophore treatment alone. MAb and 10(-10) M PMA comodulation produced only 10.6% increases in cytotoxicity compared to mAb. These data demonstrate that the moiety on NCC recognized by 5C6 may provide an activation signal for increased cytotoxicity and receptor expression. Calcium ionophore, either singly or together with mAb, provided an even stronger activation signal for increased lysis and receptor expression. PMID- 2210010 TI - Effect of malathion on humoral immune response of channel catfish. PMID- 2210011 TI - Variability of natural killer cell activity in anuran amphibians. PMID- 2210012 TI - Risk factors associated with persistence of glucose intolerance one year after gestational diabetes. AB - One hundred and fourteen women, 89 with previous gestational diabetes and 25 who showed a normal glucose tolerance during pregnancy were retested by OGTT one year postpartum. Gestational diabetics were divided into two groups according to the severity of glucose intolerance. 97.6% of mild gestational diabetics and 79.2% of severe cases returned to normality postpartum. A different behaviour of these groups was shown by comparing OGTT areas before and after delivery. Body Mass Index and the degree of severity of glucose intolerance were shown to be predictive for the persistence of the abnormality postpartum. Follow-up for three to four years was continued in 8 cases of previous severe gestational diabetes. In seven of them a glucose intolerance appeared again during the follow-up after the temporary improvement one year after delivery. PMID- 2210013 TI - [Erythrocyte aggregation in vivo and diabetic microangiopathy. Physiopathologic determinants and clinical correlations]. AB - Conjunctival angioscopy is a non invasive way for visualization and quantitative evaluation of the microcirculation. Grading red blood cell aggregation is possible in vivo using Ditzel's four grades score. The two-dimensional organization of conjunctival microvessels allows morphometric quantification of microvascular density. The aim of our study was to evaluate the determinant factors of erythrocyte aggregation and the place of conjunctival angioscopy in the early detection of diabetic microangiopathy. Conjunctival parameters were red blood cell aggregation (Ditzel's score) and morphometric evaluation of capillary, venular and arteriolar density. Criteria of diabetic microangiopathy were microalbuminuria and retinal fluorescein angiogram. Both conjunctival angioscopy and retinal angiogram were scored independently. Results obtained in 30 type 1 diabetic patients, with multifactorial statistical analysis, show that red blood cell aggregation in vivo is an essential discriminant factor for diabetic retinopathy and nephropathy. This rheological phenomenon depends more on duration of diabetes (analysis of variance p = .0005, r = .65) and metabolic control than on albuminemia or fibrinogenemia such as in non-diabetic patients. Manual morphometric data confirmed vascular rarefaction associated with excessive red blood cell aggregation (beta = .50). These results suggest that grading red blood cell aggregation in vivo is an interesting tool for physiopathological and clinical studies of diabetic microangiopathy. PMID- 2210015 TI - [Beliefs in diabetics about the etiology of their disease. Influence of ethnicity]. AB - The education of diabetics often affects the patient's life-style and habits, and the beliefs of his socio-professional and socio-cultural environment. The patient's knowledge is often satisfactory, while his behavior is inadequate. In this study, a sociologist conducted a semi-structured interview for 40 non-obese diabetic patients: 35 IDD and 5 NIDD, who had a knowledge/behavior gap. Emphasis was placed on the study of their subjective etiological beliefs. Four categories beliefs were found: stress, heredity, food and drink transgression, and fatality. Stress, which can lead to deresponsabilization, was the most frequently mentioned etiology (24 patients). Europeans cited several etiological beliefs. North Africans, in contrast, cited only one, either stress or fatality, but never heredity or food and drink transgression, probably because genetics and genealogy are not superimposable realities and because of their belief in the symbolic benefits of sugar. In conclusion, the patient's etiological beliefs may contribute to the knowledge/behavior gap. Correct information about a more rational etiology for diabetes could improve patient compliance. PMID- 2210014 TI - Autonomic neuropathy in non-insulin-dependent diabetic patients: correlation with age, sex, duration and metabolic control of diabetes. AB - The aim of this study has been to assess the prevalence of autonomic neuropathy among non-insulin dependent diabetic patients, and to determine whether a correlation could be found between autonomic impairment and the following: age, sex, duration of diabetes, body mass and metabolic control. Two hundred and twenty one non-insulin dependent patients were submitted to four cardiovascular tests: heart rate response to deep breathing and to standing up; blood pressure response to handgrip and to standing up. Sixty six percent of patients showed at least one abnormal cardiovascular response. The prevalence of autonomic impairment was higher in non-insulin dependent than in insulin-dependent diabetics. Patients were grouped according to the extent of autonomic impairment: absent (33.5%), early (27.6%), definite (3.6%), severe (4.5%). An atypical pattern (abnormality of blood pressure responses in absence of a definite abnormality of heart rate responses) was found in 30.8% of patients. Heart rate responses correlated significantly with age (p less than 0.001). No correlation between test results and duration was found in the multivariate analysis. The tests' results did not correlate with metabolic control or body mass index. Patients with symptoms of autonomic neuropathy had values for heart rate response to deep breathing and to standing significantly lower than those without (p less than 0.05). PMID- 2210016 TI - [Assessment of the use of hemoglobin AIc in diabetes mellitus screening]. AB - A population of 495 volunteer subjects who applied to the screening diabetes Centre of Hotel-Dieu hospital in Paris has been studied and divided into two samples. In the first 300 subjects sample the sensitivity and the specificity of different fasting blood glucose threshold values, of different glycosylated hemoglobin threshold levels and of various combinations of the above mentioned parameter have been evaluated as a test for diabetes diagnosis defined by a 2-hr OGTT value greater than or equal to 200 mg/dl. The predictive values for both positive and negative diagnosis were also evaluated. The combination of a fasting blood glucose greater than or equal to 120 mg/dl with a glycosylated hemoglobin greater than 5.8% was found to be the best association with a good relative specificity (97.9%), a fair sensitivity (64.7%) and a fair predictive value for a positive diagnosis (64.7%). A second sample includes 195 subjects. These were classified according to either the above criterion or either the 2-hr OGTT value greater than or equal to 200 mg/dl. A great majority of subjects (95.4%) was classified in concordance by the two methods. The characteristics of the subjects that were identically classified as diabetic subjects (n = 5) were compared to those of differently classified subjects (n = 9). Longitudinal surveys are needed in order to assess the validity of HbA1c measurement as a tool for diabetes screening by reference to unquestionable criteria of the disease. PMID- 2210017 TI - The influence of insulin antibodies on metabolic deterioration after interruption of continuous subcutaneous insulin infusion. AB - To evaluate the influence of insulin antibodies (IA) on metabolic deterioration after interruption of continuous subcutaneous insulin infusion (CSII), we studied two groups of type I diabetic patients without residual insulin secretion: group 1 (5 patients) with insulin-binding antibodies below 10% and group 2 (8 patients) with insulin-binding antibodies above 10%. We investigated the changes in blood glucose, plasma non-esterified fatty acids (NEFA), bicarbonate and glucagon after stopping insulin infusion between 08.00 h. and 14.00 h. Insulin infusion cessation resulted in: 1) a similar increase in blood glucose in both groups after 2 hours of interruption (group 1: 9.45 +/- 1.28 mmol/L versus basal levels of 6.94 +/- 0.96 mmol/L, p less than 0.05; group 2: 8.11 +/- 2.87 mmol/L versus 5.75 +/- 2.17 mmol/L, p less than 0.02) and a greater increase in blood glucose in group 1 than group 2 after 4 hours (p less than 0.05) and after 6 hours (p less than 0.05); 2) a progressive increase in NEFA in group 1 throughout the study period (08.00 h.: 0.51 +/- 0.28 mmol/L; 14.00 h: 1.44 +/- 0.45 mmol/L, p less than 0.05) that was significant after 4 and 6 hours of CSII interruption; there were no changes in NEFA in group 2; 3) plasma level of IA correlated inversely with final glycemia (r = -0.67, p less than 0.01) and final NEFA (r = 0.56, p = 0.02). We conclude that IA may play a role in slowing metabolic deterioration after CSII interruption. PMID- 2210018 TI - [Hypocarnitinemia in patients affected by a primary defect of ammonia metabolism treated with sodium benzoate]. AB - We have studied the plasma and urinary levels of free and esterified carnitine in 18 patients affected by a primary defect of ammonia metabolism, which had been managed with or without a therapy of sodium benzoate. None of these patients presented with any acute neurologic or digestive symptoms during the study. Our group of non-treated patients showed an increase in the levels of plasma esterified carnitine and an elevation of urinary concentration of free carnitine, while the levels of urinary esterified carnitine clearly approached the superior limits of normal values. The group treated with sodium benzoate showed a more profoundly disturbed plasma and urinary carnitine profile: a significantly lower plasma and urinary free carnitine, accompanied by a clearly increased esterified/free carnitine ratio. We did not find any evidence of a relationship between the plasma levels of free or esterified carnitine and the protein intake or the plasma ammonia concentration. We are proposing a hypothesis to explain the hypocarnitinemia seen in our patients being treated with benzoate, along with other modifications observed in the carnitine profile. We believe that a supplement of carnitine could be beneficial in the management of some of these patients. PMID- 2210019 TI - Sex-related differences in peripheral glucose metabolism in normal subjects. AB - The metabolic response of muscle tissue to glucose ingestion was studied in 10 normal men (M) and women (F) by using the forearm balance technique and indirect calorimetry simultaneously. During the 3 hours after a 75 g--oral glucose load, glucose uptake per unit muscle mass was significantly higher in women than in men, F = 187.3 +/- 26.9 vs M = 116.7 +/- 9.5 mg/100 g forearm muscle (P less than 0.05). A significant difference in muscle glucose fate was also observed since the amount of glucose utilized through a nonoxidative pathway was significantly higher in women, F = 84.5 +/- 2.6% (161.8 +/- 27.3 mg/100 g forearm muscle) vs M = 75.3 +/- 2.2% (87.2 +/- 8.6 mg/100 g forearm muscle) (P less than 0.05), whereas the amount of glucose oxidized in relation to glucose uptake was significantly higher in men, M = 24.7 +/- 2.2% (28.2 +/- 3.2 mg/100 g forearm muscle) vs F = 15.5 +/- 2.6% (27.8 +/- 5.4 mg/100 g forearm muscle) (P less than 0.05). No significant differences in insulin response to glucose ingestion were detected between groups. The women showed greater suppression of serum free fatty acids (FFA) levels in relation to basal levels than men. We conclude that: 1) after ingesting 75 g glucose, normal women showed greater glucose uptake per unit muscle mass than normal men, 2) for 3 hours after the ingestion of 75 g glucose, the predominant tendency toward utilizing glucose by a nonoxidative pathway is more marked in normal women than in normal men, and 3) the higher glucose uptake per unit muscle mass in the female group in the presence of an insulin response not significantly different from that of the male group suggests that muscle insulin sensitivity is greater in normal women. PMID- 2210020 TI - In vivo and in vitro characterization of insulin resistance in three cases of lipoatrophic diabetes. AB - Insulin resistance was explored in vivo and in vitro in 3 lipoatrophic diabetic girls (12, 15 and 19 years old = L1, L2 and L3). Patients L1 and L2 were explored with fasting hyperglycaemia (9 mmol/l); patient L3 was normoglycaemic. All had abnormal OGTT with marked hyperinsulinemia. Their basal glucose productions, measured by [6,6(-2)H] glucose constant infusion, were 3.3, 2.6 and 3.4 mg kg-1 min-1, respectively; they did not correlate with fasting plasma glucose. Glucose production in response to a 2 mg kg-1 min- unlabeled glucose infusion, was normally suppressed in L2, but was incompletely suppressed (by 1.5 mg kg-1 min-1) in L1 and L3. The dose-response curve during hyperinsulinemic euglycaemic clamp at 1, 2 and 10 mU kg-1 min-1 insulin infusion was shifted to the right in all three patients. However the maximal glucose disposal rates were close to normal (9 and 9 mg kg-1 min-1) in L1 and L3, while it remained very low (3.6 mg kg-1 min 1 at 10 mU kg-1 min-1 insulin infusion) in L2. The endogenous insulin secretion (plasma C-peptide) was also incompletely suppressed during insulin infusion. Thus, the in vivo insulin resistance of lipoatrophic diabetes concerns not only glucose disposal but also hepatic glucose output and insulin secretion; in addition, the alterations of glucose metabolism were not the same in all subjects. The in vitro studies showed no pre-receptor defect (anti-insulin antibodies, insulin receptor antibodies). Insulin binding to erythrocytes and cultured fibroblasts was normal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210021 TI - The effect of oxytocin on the plasma glucagon response to insulin-induced hypoglycaemia in man. AB - The presence of the classical neurohypophyseal hormone oxytocin has recently been described in the human pancreas in considerably higher concentrations than those found in peripheral plasma. Evidence in animals and man suggests that oxytocin can directly stimulate the secretion of glucagon from pancreatic islets. In order to investigate a possible paracrine role for oxytocin in the regulation of glucagon secretion we have studied the effect of oxytocin on the plasma glucagon response to insulin-induced hypoglycaemia in 10 lean fasted male subjects. Intravenous insulin tests were performed in random order with or without oxytocin infusion (2 U bolus injection; 111 mU/min for 2 hours). Blood sugar nadir occurred at the onset of symptoms (time S) with no significant differences between oxytocin and saline infusions (saline S = 24 +/- 2.3 min; oxytocin S = 23.3 +/- 2.7 min). There was no significant change in peripheral plasma oxytocin concentrations during saline infusion. During the oxytocin infusion plasma oxytocin concentrations rose from 1.05 +/- 0.1 (mean +/- SEM) pmol/l to a peak of 632 +/- 179 pmol/l and remained elevated throughout the study. Peak plasma glucagon concentrations occurred at S + 10 mins with no significant differences in peak values (saline 200 +/- 26.3 pg/ml; oxytocin 207 +/- 23.6 pg/ml) between saline and oxytocin infusions. The data suggest that oxytocin at concentrations up to 6.3 X 10(-10) M has no effect on the decline or recovery of blood glucose concentrations or on the plasma glucagon response to insulin-induced hypoglycaemia. PMID- 2210022 TI - [Should one treat hyperlipidemia in diabetes, and how?]. PMID- 2210023 TI - [How useful is an inquiry about family history in type 2 diabetes?]. PMID- 2210024 TI - [Evaluation of a quick screening test of microalbuminuria in diabetology]. AB - Disclosure of microalbuminuria gives a hope to improve renal and perhaps cardiovascular outcome of diabetes mellitus by the mean of an early treatment. We studied in 30 diabetic patients for each sex, consecutively admitted to hospital the efficacy of a colorimetric tablet-test for quick screening of microalbuminuria. The results obtained from a 24 hours-urine collection are compared to those observed with a reference radio-immunologic method. In this population whose prevalence for microalbuminuria over 15 micrograms/mn is 30%, the test shows a sensibility and a negative predictive value of 100%, but a specificity and a positive predictive value of about 40%. Else, intensity of positivity follows systolic blood pressure and creatininemia increase. If the good and cheap screening value of the test can be acknowledged, its positivity needs however a precise evaluation by a reference assay before therapeutic decision. PMID- 2210025 TI - Quinapril reduces arterial blood pressure and improves metabolic control in elderly hypertensive diabetic patients. PMID- 2210026 TI - [Inhibitors of the conversion enzyme and glycoregulation]. PMID- 2210027 TI - 1,25-Dihydroxyvitamin D3 suppresses dexamethasone effects on calcitonin secretion. AB - 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) and dexamethasone (DEX) influence synthesis and secretion of various hormones. Recent reports concerning the interaction of the two steroids revealed opposite--agonistic as well as antagonistic--effects in different biological systems. As calcitonin (CT) gene expression is affected by both agents, inhibited by 1,25(OH)2D3 and stimulated by DEX, we utilized CT secretion and storage as a model to study the combined effects of the two hormones. A human C cell carcinoma cell line (TT) was used, incubating the cells for a period of 4 days with 1,25(OH)2D3 and DEX alone and in combination. 1,25(OH)2D3 resulted in a decrease, whereas DEX resulted in a increase of CT secretion and content. Combining the two steroids, 1,25(OH)2D3 surprisingly abolished the stimulation of DEX on CT secretion and content. The underlying mechanism is yet unclear and could be envisioned to include steroid receptor regulation or gene transcription. PMID- 2210028 TI - Autoinduction of estrogen receptor is associated with FOSP-1 mRNA induction by estrogen in primary cultures of Xenopus oviduct cells. AB - The number of nuclear and cytosolic estrogen receptors (ER) per cell and the steady-state levels of the mRNA encoding a tissue-specific, estrogen-inducible protein (FOSP-1) were measured as a function of time following the addition of estradiol-17 beta (E2) to primary cultures of Xenopus oviduct cells. After a lag period of about 12 h, 10(-9) to 10(-7) M E2 caused a 10 to 15-fold increase in FOSP-1 mRNA by 60 h, whereas it was only 2-fold with 10(-7) M progesterone. Under the same conditions, E2 doubled its own total receptor content within the first 12 h, reaching a 4-fold increase in nuclear ER by 48 h. Cycloheximide treatment in the presence of 10(-7) M estradiol reduced the functional ER content by 75.90%. Treatment with the anti-estrogen ICI 164,384 of oviduct cells in which FOSP-1 mRNA was pre-induced to high levels with the hormones caused a drastic reduction in nuclear ER and a total loss of FOSP-1 mRNA in 72 h. The close correlation between the kinetics of autoinduction of ER and the induction of FOSP 1 mRNA, as was shown earlier for vitellogenin mRNA in hepatocytes (Perlman et al. (1984) Mol. Cell. Endocrinol. 38, 151-161), strongly suggests that Xenopus egg protein gene activation by estrogen requires the up-regulation of its own receptor by the hormone. PMID- 2210029 TI - Involvement of cytoskeleton in polypeptide hormone secretion from the anterior pituitary lobe: a review. PMID- 2210030 TI - Thyroid hormone regulates expression of the thyrotropin beta-subunit gene from both transcription start sites in the mouse and rat. AB - Thyroid hormones suppress transcription of the gene for the beta-subunit of thyrotropin (TSH beta). Since the TSH beta gene in both the mouse and the rat contains two start sites of transcription in exon 1, we have investigated whether expression of the gene from each start site is differentially regulated by thyroid hormones in each species. RNase protection analysis was used to assay the levels of mRNA specifically transcribed from the upstream (TSS 1) and downstream (TSS 2) transcription start sites in the mouse and rat pituitary. In euthyroid and hypothyroid pituitaries there was an approximately 5-fold and 2-fold greater abundance of mRNA derived from TSS 2 than TSS 1, respectively. Hypothyroidism induced an 18- and a 9-fold increase in TSH beta gene expression from TSS 1 and TSS 2, respectively. Treatment of hypothyroid animals for 1 day with triiodothyronine (T3) reduced expression from both start sites by about 50%; after 4 days of T3 treatment, TSH beta mRNAs derived from both start sites were below detectable levels. These results were confirmed in the rat by primer extension analysis. Expression from TSS 1 in the mouse was also shown to be dependent on thyroid status using the polymerase chain reaction (PCR) technique. In contrast to previous results from primer extension studies, PCR analysis demonstrated that alternative splicing of the TSH beta RNA primary transcript can occur when transcription is initiated at the upstream start site. We conclude that, in both the mouse and the rat pituitary, expression of the TSH beta gene from both transcription start sites is regulated by thyroid hormones. PMID- 2210031 TI - Full-length sequence and in vitro expression of rainbow trout estrogen receptor cDNA. AB - We previously reported the isolation of a partial cDNA clone encoding the rainbow trout estrogen receptor (rtER). A 0.4 kb 5'-end insert of this cDNA was used to screen the trout liver lambda gt10 cDNA library, and a full-length cDNA was isolated and sequenced. The principal structural characteristics of the complete coding sequence of the rtER are: first a remarkable homology of the DNA binding (C) and hormone binding (E) domains with those of other species, and second the lack of an A region, the function of which is not yet known but which is well conserved in other species. In vitro expression of the full-length rtER cDNA was carried out after transcription by T7 RNA polymerase and translation in rabbit reticulocyte lysate. Translation product analysis shows three major proteins, the largest one of which probably corresponds to the translation of the complete open reading frame of mRNA. The rtER in vitro translation products specifically bind estrogens (estradiol and diethylstilbestrol), without competition from testosterone or cortisol. The equilibrium dissociation constant (Kd), deduced from the Scatchard plot, is in the same order of magnitude as those determined heretofore in salmon livers during classical experiments. The tissue distribution of rtER mRNA shows that the same mRNA size (3.5 kb) is also present in the pituitary and hypothalamus. However, in the pituitary, a smaller sized mRNA (1.4 kb) is also detected. PMID- 2210032 TI - Processing of the lipid-mobilizing peptide beta-lipotropin in rabbit adipose tissue. AB - beta-Lipotropin, a pituitary peptide, is a strong stimulator of lipolysis in rabbit adipose tissue. This polypeptide is shown to be degraded by intact fat pads, homogenized adipose tissue and adipocytes of the rabbit dependent on the amount of adipose tissue, time and the pH of the incubation medium. In subcellular fractions of rabbit adipocytes the proteolytic activity could be localized into the cytosol and the microsomal fraction. To obtain information about the processing of beta-lipotropin in its target cell lipolysis and degradation of this polypeptide were investigated in the presence of inhibitors of distinct cellular mechanisms and in different physiological states such as obesity and starvation. Thus, the stronger lipolytic response in adipocytes from obese rabbits respectively animals fed ad libitum was accompanied by a significantly increased degradation in comparison to lean respectively starved rabbits. The six lysosomotropic agents (chloroquine, NH4Cl, propranolol, quinacrine, acridine orange and tetracaine), the proteinase inhibitors alpha 2 macroglobulin and monodansylcadaverine, cellular ATP depletion by 2-deoxy-D glucose and 2,4-dinitrophenol and the omission of Ca2+ ions from the incubation medium inhibited dose-dependently the lipolytic activity as well as the degradation of beta-lipotropin in intact and homogenized adipose tissue. Inhibitors of the cytoskeleton such as colchicine, cytochalasin B, vinblastine and concanavalin A also reduced lipolysis but only the degradation in intact adipose tissue. It can be concluded that after receptor-mediated uptake the cytoskeleton and lysosomal proteases are involved in the processing of beta lipotropin. PMID- 2210033 TI - Triiodothyronine inhibits transcription from the human growth hormone promoter. AB - Three DNA constructs, the natural human growth hormone gene (hGH-hGH) its 500 bp promoter linked to the chloramphenicol acetyl transferase reporter gene (hGH CAT), and its structural part linked to the herpes virus thymidine kinase promoter (TK-hGH) were introduced into rat pituitary GC cells by DEAE-dextran transfection. Transient expression was followed as a function of triiodothyronine (T3) concentration. The hGH-CAT expression was specifically inhibited by T3 following a typical dose-response curve while hGH-GH gene expression was not significantly modified. The transient expression of TK-hGH increased as a function of T3 concentration. These results indicate that T3 exerts two opposite effects on hGH gene expression. First, it down-regulates expression by acting on the promoter; second, it up-regulates expression by acting on the structural part of the gene. These action could be due to regulation of transcription and mRNA stabilization, respectively. PMID- 2210034 TI - The origins of neural crest cells in the axolotl. AB - We address the question of whether neural crest cells originate from the neural plate, from the epidermis, or from both of these tissues. Our past studies revealed that a neural fold and neural crest cells could arise at any boundary created between epidermis and neural plate. To examine further the formation of neural crest cells at newly created boundaries in embryos of a urodele (Ambystoma mexicanum), we replace a portion of the neural folds of an albino host with either epidermis or neural plate from a normally pigmented donor. We then look for cells that contain pigment granules in the neural crest and its derivatives in intact and sectioned host embryos. By tracing cells in this manner, we find that cells from neural plate transplants give rise to melanocytes and (in one case) become part of a spinal ganglion, and we find that epidermal transplants contribute cells to the spinal and cranial ganglia. Thus neural crest cells arise from both the neural plate and the epidermis. These results also indicate that neural crest induction is (at least partially) governed by local reciprocal interactions between epidermis and neural plate at their common boundary. PMID- 2210035 TI - Developmental mechanisms regulating the rapid decrease in a cohesion glycoprotein mRNA in Dictyostelium function primarily at the level of mRNA degradation. AB - During the morphogenetic program in Dictyostelium discoideum, the transcript of the gene encoding the cohesion glycoprotein gp80 accumulates to a maximum level between 4 and 6 hr, (just prior to the onset of aggregation), remains high between 6 and 10 hr (the ripple to loose aggregate stages), and then decreases to less than 10% of the maximum level between 10 and 12 hr (the tight aggregate stage). The level of gp80 transcript also decreases precipitously at the time of the erasure event in the program of dedifferentiation, or when cAMP is added to a dedifferentiating cell population prior to the erasure event. In the dedifferentiation-defective mutant HI4, the cAMP-stimulated system for rapidly reducing the level of gp80 transcript is intact, but the mechanism functioning at the time of the erasure event is defective, demonstrating that the two reduction mechanisms are dissociable. By comparing the levels of gp80 transcript with the levels of in vitro transcription of the gene in isolated nuclei, it is demonstrated that the rapid reduction of gp80 transcript immediately after aggregation and immediately after addition of 10(-4) M cAMP are the result of increased transcript degradation. The rapid reduction of gp80 transcript at the erasure event may also be due to increased transcript degradation, but transcriptional regulation cannot be completely ruled out in this case. PMID- 2210036 TI - Elongation factor 1 alpha (EF-1 alpha) is concentrated in the Balbiani body and accumulates coordinately with the ribosomes during oogenesis of Xenopus laevis. AB - In Xenopus laevis oocytes two distinct systems catalyze the mRNA-dependent binding of aminoacyl tRNA to the A site of ribosomes. These systems are elongation factor 1 alpha (EF-1 alpha) and the 42S nucleoprotein particle. This particle is also implicated in the long-term storage of 5S RNA and aminoacyl tRNA during early oogenesis. We report here that the ribosomes and the storage particles are distributed uniformly in the cytoplasm of previtellogenic (stage I) oocytes. In contrast, EF-1 alpha is concentrated in a small region of the cytoplasm, known as the mitochondrial mass or Balbiani body. When the Balbiani body disperses in early vitellogenic oocytes (stage II), EF-1 alpha becomes evenly distributed in the cytoplasm. The main phase of EF-1 alpha accumulation follows the disappearance of the 42S particles (stage II), but coincides with the main phase of ribosome accumulation (stages III and IV). PMID- 2210038 TI - Developmental regulation of a cadherin during the differentiation of skeletal myoblasts. AB - Cadherins are a family of integral membrane glycoproteins which mediate calcium dependent intercellular adhesion in vertebrate species. Here we present evidence that fusion-competent rat L6 myoblasts express a cadherin (Mr 127 kDa). The levels of this cadherin were found to be developmentally regulated. Maximal levels were expressed prior to fusion. The increase in cadherin levels observed during differentiation was prevented by the differentiation inhibitor, 5-bromo-2' deoxyuridine. L6 myoblasts grown in the presence of anti-cadherin antibodies exhibited an altered morphology in comparison to control cultures, coupled with decreased myoblast fusion. These data indicate that the developmental regulation of cadherin is part of the program of terminal differentiation of skeletal myoblasts, and that cadherins are involved in the process of myoblast fusion. PMID- 2210037 TI - Ontogeny of placental lactogen-I and placental lactogen-II expression in the developing rat placenta. AB - The purpose of this investigation was to identify the cellular origin, and the temporal and regional characteristics of placental lactogen-I (PL-I) and placental lactogen-II (PL-II) expression during placental development in the rat. PL-I and PL-II mRNA expression were assessed by Northern blot analysis and in situ hybridization. PL-I and PL-II protein expression were determined by Western blot and immunocytochemical analyses. PL-I mRNA was first detected by in situ hybridization at Day 6 of gestation in mural trophoblast giant cells and a day later, PL-I protein was first detected by immunocytochemistry. PL-I immunostaining extended to the polar trophoblast giant cells as gestation advanced. Polar trophoblast giant cell staining for PL-I was not as intense as the mural trophoblast giant cell staining. Northern and Western blot analyses confirmed the asymmetric distribution of PL-I expression. PL-I mRNA migrated as a 1-kb species and PL-I protein migrated as 30- and 36-40-kDa forms. PL-I expression abruptly declined at Day 12, and by Day 13, PL-I was not detectable. PL-II protein was first detectable at Day 11 of gestation and was localized to trophoblast giant cells. PL-II mRNA could be detected at Day 10 of gestation. Northern and Western blot analyses indicated that PL-II expression significantly increased as gestation advanced and that PL-II expression was asymmetrically distributed similar to PL-I. PL-II mRNA migrated as a 1-kb species and PL-II protein migrated as a 25-kDa species. Blastocysts recovered on Day 4 of gestation initially showed no detectable expression of PL-I or PL-II; however, after 2 days of culture PL-I protein expression was detectable. Biochemical characteristics of PL-I synthesized and secreted by blastocyst outgrowths were similar to PL-I synthesized and secreted by Day 10 placental explants. In summary, (1) PL-I and PL-II are produced by trophoblast giant cells of the developing placenta, (2) PL I and PL-II exhibit distinct temporal and regional patterns of expression during placental morphogenesis, and (3) PL-I expression by blastocyst outgrowths can be induced in vitro, whereas a more complex array of signals appears necessary for induction of PL-II expression. PMID- 2210039 TI - Analysis of cytoplasmic activity dependent on the Drosophila terminal pattern gene torso. AB - Cytoplasm from wildtype Drosophila embryos was transplanted into torso (tor) mutant embryos to determine the distribution of terminal rescuing activity at the cleavage stage. Although posterior and lateral wildtype cytoplasm contained rescuing activity that restored posterior terminal (telson) structures Klingler et al. (1988, Nature (London) 335, 275-277) this rescuing activity was not found in anterior cytoplasm. Similarly, transplantation of anterior and lateral wildtype cytoplasm into the anterior of tor embryos rescued anterior terminal (acron) structures, whereas posterior cytoplasm did not. This failure of reciprocal rescue is due to the presence of the products of the anterior and posterior classes of genes, because anterior cytoplasm from bicoid mutant embryos restored the telson in the posterior as well as the acron in the anterior of tor embryos, and because posterior cytoplasm from nanos embryos rescued the acron in the anterior as well as the telson in the posterior of tor embryos. Therefore terminal rescuing activity is evenly distributed throughout the cleavage stage embryo as anticipated from molecular studies. PMID- 2210040 TI - Osteogenic cell lineage analysis is facilitated by organ cultures of embryonic chick periosteum. AB - Monoclonal antibodies against the surface of embryonic osteogenic cells (SB-1, SB 2, SB-3, and SB-5) have been used to characterize the sequence of transitions involved in the osteogenic cell lineage. In the present study, immunohistochemical analyses of the expression of osteogenic cell surface antigens in organ cultures of folded chick periosteum were performed. Unlike traditional culture methods using isolated osteoblastic cells, periosteal explants form a mineralized bone tissue in 4 to 6 days which is virtually identical to the in vivo counterpart. Examination of fresh explants confirm that no mature osteoblastic cells were present, although a discontinuous layer of preosteoblasts was evident. As the wave of osteodifferentiation swept through the cultured tissue, antibody SB-1 reacted with the surface of a large family of cells associated with the developing bone. Antibodies SB-3 and SB-2 reacted with progressively smaller subsets of cells, namely those in successively closer physical association with the newly formed and mineralizing bone. Cells recently encased in bone matrix were stained by both SB-2 and SB-5 antibodies, while those cells deep within the matrix reacted only with antibody SB-5. Analysis of this culture model allows dissection of the discrete cellular transition steps of osteogenesis, and reveals that osteogenic precursor cells proceed through the unique lineage stages which have been documented for in vivo osteogenesis. This culture system has furthermore provided evidence which is used to refine our understanding of the osteogenic cell lineage. PMID- 2210041 TI - Membrane conductance patterns during fertilization are sperm dependent in two sea urchin species. AB - The influence of the egg and sperm on the conductance changes at fertilization in the sea urchin were investigated through cross-fertilization of two Hawaiian species, Tripneustes gratilla and Pseudoboletia indiana. The current-voltage (I V) relation, measured in voltage-clamped eggs at intervals over the period 2-16 min following the rise to a positive membrane potential that signals sperm attachment, differs significantly in the two species. The magnitude of the conductance change depends on the species of the fertilizing sperm in both homologous and heterologous crosses. This supports the hypothesis that currents during this period arise from sperm membrane channels incorporated into the egg at sperm-egg fusion. Measurements of conductance during the first 90 sec, which includes the period of the major inward current correlated with cortical granule breakdown and elevation of the fertilization envelope, showed that the magnitude and timing of the maximum current also differed in the two species. This conductance change presumably involves an activation of egg membrane channels initiated by the sperm and would be expected to be characteristic of the egg species. However, in cross-fertilized eggs the magnitude and timing of the conductance change over this period also depends on the species of the sperm with little identifiable egg contribution, indicating that the fertilizing sperm can modulate the egg response to influence these events. PMID- 2210042 TI - 1-Methyladenine can consistently induce a fura-detectable transient calcium increase which is neither necessary nor sufficient for maturation in oocytes of the starfish Asterina miniata. AB - In starfish oocytes a calcium transient can consistently be detected with the dye fura-2 in response to perfusion of threshold levels of 1-methyladenine, the hormone responsible for induction of meiotic maturation. The calcium transient cannot be detected when the hormone is allowed to slowly diffuse to the oocyte, and the hormone-induced calcium transient can be inhibited by preperfusion of the oocyte with subthreshold levels of hormone. The calcium transient is shown to be unnecessary for maturation by eliciting maturation in situations that are not associated with a calcium transient, and the calcium transient is shown to be insufficient for maturation by eliciting a calcium transient and washing the hormone off the oocytes before the end of the hormone-dependent period. A mechanism is suggested to explain why some investigators have detected transient calcium rises during induction of oocyte maturation while others have not. PMID- 2210043 TI - Formation and survival of a postsynaptic specialization in cultures of embryonic Xenopus nerve and muscle cells. AB - The formation and survival of nerve-induced clusters of acetylcholine receptors (AChRs) was monitored over a synaptogenic period of several days in cultures of myotomal muscle cells and spinal cord neurons derived from embryos of Xenopus laevis. AChRs were labeled with fluorescent alpha-bungarotoxin so that neurite associated receptor patches (NARPs) could be viewed at daily intervals throughout the neuritic arbor of selected neurons. To avoid bleaching the NARPs and damaging the neurons, the intensity of the fluorescence excitation was reduced to 3%. Images were digitized and NARPs were measured with a computer-based image analysis system. Virtually all newly formed NARPs (greater than 90%) were detected at the same time as neurite-muscle contact and in the same proximal distal sequence as neuritic growth. Those which formed in 6- to 13-day-old cocultures had similar distributions with respect to length, area, intensity, and area X intensity to those which formed in 1- to 2-day-old cocultures. NARPs exhibited variable daily changes in these parameters but on average they grew and reached close to their ultimate values within 1-2 days. Almost all (greater than 95%) survived as long as their contacts. In cases where NARP formation occurred on the same muscle on 2 or more different days, the ones which formed first were the most extensive. Spontaneous neurite withdrawal occurred mainly from young NARPs and resulted in their rapid disappearance. It is suggested that during the period when neurons grow and make new contacts with muscle cells there is no substantial change in their capacity to trigger the formation of new synaptic sites and maintain preexisting ones, and that the first-forming synapses on a muscle cell tend to be the largest because muscle cells have a limited capacity to generate postsynaptic membrane. Additional implications of the findings for synapse formation and elimination are discussed. PMID- 2210044 TI - Regulation of proliferation of embryonic heart mesenchyme: role of transforming growth factor-beta 1 and the interstitial matrix. AB - Proliferation of atrioventricular cushion mesenchyme of the embryonic avian heart maintained in three-dimensional aggregate culture is stimulated by interaction with the interstitial matrix. Chicken serum or transforming growth factor-beta 1, which stimulates proliferation, induces matrix deposition in regions of the aggregate showing high labeling indices with tritiated thymidine. Dispersed heart mesenchyme interstitial matrix introduced into serum-free culture is incorporated into the aggregate and stimulates cellular proliferation similar to serum or transforming growth factor-beta 1. Proliferation is reversibly inhibited by the peptide Gly-Arg-Gly-Asp-Ser-Pro. It is suggested that transforming growth factor beta 1 stimulates the production of interstitial matrix and that a sufficient stimulus for proliferation in this system is the presence of the matrix, which acts as the adhesive support for cellular anchorage. PMID- 2210045 TI - A novel oncofetal gene is expressed in a stage-specific manner in murine embryonic development. AB - A novel cDNA clone obtained from a murine T-lymphoma library hybridizes to transcripts expressed in placenta and embryos (Pem) in a stage-specific manner. The Pem cDNA sequence predicts an intracellular hydrophilic protein with no significant sequence similarity to other DNA or protein sequences. Pem transcripts are abundant in 7- and 8-day mouse embryos, but decrease precipitously thereafter. On Day 9 they become abundant in placenta and yolk sac, persisting there until parturition. Although Pem transcripts are present in immortalized and tumorigenic cell lines from several different cell lineages, they are not detectable in any of 15 adult tissues tested. The expression of Pem during fetal development and its presence in immortalized and neoplastic cell lines is consistent with the properties expected of an "oncofetal" gene. PMID- 2210046 TI - Activity level and auditory responsiveness in neonatal chickens. AB - The effects of prestimulus activity levels on auditory responsiveness were evaluated in newborn chickens. Rates of peeping were used as measures of prestimulus activity, and delays in the otherwise ongoing vocalizations were used as measures of responsiveness. Results show increased responsiveness to pure tones at intermediate levels of prestimulus activity. Responsiveness is reduced during periods of high and low activity. The effect is strongest just prior to the stimulus. Similar analyses could be useful in other studies that depend on the changing rate of repetitive responses, such as gross body movements, head turning, heart rate, and perhaps neural potentials. Some of the variability in the responses of young subjects can be controlled by measuring the subject's activity at the time a stimulus is presented. PMID- 2210047 TI - Responses of infant mice to odors of urine from infanticidal, noninfanticidal, and paternal male mice. AB - Infant mice responded differently to the odors of urine from isolated infanticidal, isolated-noninfanticidal, and parental males. More ultrasonic vocalizations were produced in response to urine odors of parental males than to those of isolated-infanticidal males and more to infanticidal than to noninfanticidal males. Infants became agitated in the presence of urine odors of infanticidal males and moved away from the odor source whereas they tended to remain stationary in response to urine odors of parental males. The response to urine odors of noninfanticidal males was intermediate. These data support the hypothesis that infanticidal and parental states have different physiological bases and that this physiological difference results in different chemical composition of urine. The data failed to support the hypothesis that infants will attempt to conceal themselves from infanticidal males by remaining quiet. PMID- 2210048 TI - Morphine treatment and reproductive condition alter olfactory preferences for pup and adult male odors in female rats. AB - Administration of morphine sulfate (MS) to pregnancy-terminated and postpartum lactating female rats disrupts both maternal behavior and postpartum aggression. Since the display of these behaviors may be heavily dependent on olfactory cues provided by the stimulus animals (rat pups and adult male rats, respectively), we examined whether MS was affecting the perception of the olfactory stimuli, and whether olfactory perception was modified by reproductive condition. In Experiment 1, lactating rats had their pups removed and were injected with MS (5.0 mg/kg, sc.) or saline. 60 min later they were placed into a two-choice apparatus, one side of which contained bedding soiled by neonates and the other clean bedding. Time spent on each side was recorded for a total of 5 min (300 s; chance = 150 s). Saline-treated mothers spent significantly more time on the pup odor side, whereas MS-treated females spent significantly less. In Experiment 2, lactating females were treated with MS or saline and exposed to male odors (soiled bedding). MS significantly increased time spent on the side with male odors; when treated with saline, time spent was significantly reduced. Thus, in lactating rats. MS creates an aversion for pup odors while reducing the female's normal aversion toward male odors. In Experiment 3, ovariectomized (ovx) virgin females expressed neither an aversion nor a preference for the odor of pups following saline administration. After MS treatment, however, the virgins showed a distinct preference for pup odors. When exposed to male odors in Experiment 4 ovx virgins showed a marked preference for male odors after MS treatment, and neither a preference nor an aversion after saline. Experiment 5 examined pup odor preferences in intact virgins, early (Day 7), middle (Day 14), late-pregnant (Day 21), and prepartum (Day 22) rats. The pup odor preferences of virgin, Day 7, Day 14, and Day 21 pregnant rats were not different and generally were at chance levels. Day 22 pregnant females exhibited a marked preference for pup odors compared to chance levels, as well as compared to the other four groups. These findings suggest that opiates and endogenous opioids may regulate olfactory preferences and that alterations in this system may underlie normal behavioral changes toward conspecifics prepartum as well as during lactation. PMID- 2210049 TI - Maternal behavior variations and adaptations, and pup development within litters of various sizes in Wistar rat. AB - Variations of two maternal behavior components (time spent with litter and rapidity of pup retrieving) as well as certain physical and developmental characteristics of pups (weight, relative weight gain, and neuromotor maturation) in rats were simultaneously studied in 29 various-sized litters in which interindividual variations were not experimentally amplified. Results showed mothers' behavioral adaptations to litters' characteristics (size and weight). Time spent with young was linked to litter size, whereas rapidity of pup retrieving was related to the pups' physical characteristic. Beyond these adaptive variabilities, residual variations subsisted between mothers. These variations were determinant for differences in pup development for only one component: the time that mothers spent with their litters, while pup retrieving component variations did not have any effect. PMID- 2210050 TI - Selective pup retrieving by mother rats: sex and early development characteristics as discrimination factors. AB - Discrimination between own-litter pups by mother rats was studied over 14 litters, in a standardized situation eliciting maternal pup-retrieving activity. Results showed some consistency in the order in which pups of a litter were retrieved by the mother in the 4-day and 9-day tests and that this order was related to certain characteristics of the pups: 1) on Day 4 and 9, the best developed pups of the litter (in terms of body weight and neuromotor behaviors) were first retrieved; 2) on Day 9, sex of pups became an additional discrimination factor, as males were retrieved before their female littermates. Variables included in these global discrimination factors and possible consequences of such differential mother-pups interactions are discussed. PMID- 2210051 TI - Insulin-mimetic effects of vanadate. Possible implications for future treatment of diabetes. AB - Vanadate ions, low-molecular-weight phosphate analogues, mimic most of the rapid actions of insulin in various cell types. When administered orally to diabetic hyperglycemic rats, vanadate reaches the circulation, mimics insulin stimulation of glucose uptake and metabolism, and leads to normoglycemic and partial anabolic states. In addition, vanadate restores tissue responsiveness to insulin and hepatic glycogen levels and activates new synthesis of key enzymes for carbohydrate metabolism. This suggests that correcting hyperglycemia is sufficient to correct the typical metabolic alterations found in streptozocin induced diabetic rats. Several weeks of oral administration of vanadate to diabetic rats has not produced detectable liver or kidney toxicity. The mechanism by which vanadate mimics the actions of insulin is still obscure. Unlike insulin, vanadate does not seem to stimulate the autophosphorylation and endogenous tyrosine phosphorylation of insulin-receptor kinase or other intracellular proteins either directly or by virtue of its known inhibitory effect on protein phosphotyrosine phosphatase. Results from many studies support a model in which vanadate activates glucose metabolism by either utilizing an alternative (insulin independent) cascade or bypassing the early events of the insulin-dependent cascade. Either of these possibilities is of clinical importance, because early insulin events may become defective, as a result of severe hyperinsulinemia, and may contribute to insulin resistance. Alternative pathways by which vanadate may stimulate glucose metabolism, e.g., by increasing intracellular Ca2+ levels and/or regulating intracellular and intravesicular pH, are discussed. From a clinical perspective, studies should be continued in evaluating the level of vanadate toxicity after prolonged treatment and searching for agents that potentiate its insulin mimetic actions in vitro and in vivo. PMID- 2210052 TI - Association of elevated fasting C-peptide level and increased intra-abdominal fat distribution with development of NIDDM in Japanese-American men. AB - The Japanese-American population of King County, Washington, is known to have a high prevalence of non-insulin-dependent diabetes mellitus (NIDDM). As part of a community-based study, we reexamined 146 second-generation Japanese-American men who had been initially classified as nondiabetic. At a mean follow-up period of 30 mo, 15 men had developed NIDDM, and 131 remained nondiabetic. The variables measured at the initial visit that distinguished the 15 diabetic men from the 131 nondiabetic men were older age, higher serum glucose level at 2 h after 75 g oral glucose, higher fasting plasma C-peptide level, and increased cross-sectional intra-abdominal fat area as determined by computed tomography. Both older age and higher 2-h glucose levels are variables that have been associated with the development of NIDDM, but the association of higher fasting C-peptide level and greater intra-abdominal fat area with subsequent development of NIDDM were new observations. The elevated fasting C-peptide level persisted after adjustment for fasting serum glucose. The elevated C-peptide level represents hypersecretion of insulin and was interpreted to reflect a compensatory response to an underlying insulin-resistant state that antedates the development of NIDDM. The fasting C peptide level was correlated with the intra-abdominal fat area, suggesting that the intra-abdominal fat area may be associated with insulin resistance. Thus, in individuals who develop NIDDM, insulin resistance, increased insulin secretion, and increased intra-abdominal fat are present before diabetic glucose tolerance can be demonstrated. PMID- 2210053 TI - Pulsatile insulin secretion in isolated rat islets. AB - The pancreas secretes insulin in an oscillatory fashion, but the precise site of the pacemaker for pulsatile insulin secretion has not been identified. These studies were designed to determine whether islets also secrete insulin in a pulsatile fashion if they are isolated from their pancreatic milieu. Isolated rat islets (80-100) were perifused 8 h in culture medium after overnight incubation, and samples were collected at 3.3-min intervals. Insulin secretion was evaluated for pulsatility with the Clifton Cycle Detection Program. Perifusion of islets was associated with a spontaneous, persistent, and regular pulsatility of insulin secretion, which was observed in all conditions tested. Perifusion with medium containing 5.5 mM glucose (n = 11) demonstrated oscillations with a mean periodicity of 17.6 +/- 1.1 min and a mean amplitude of 4.8 +/- 0.4 microU/ml when overall mean insulin concentration was 16.7 +/- 2.4 microU/ml. When the glucose concentration was 16.7 mM (n = 9), overall mean insulin concentration was 54.4 +/- 2.6 microU/ml, with increases in periodicity (22.0 +/- 1.3 min) and amplitude (10.7 +/- 0.5 microU/ml). All measurements were significantly different from those observed during perifusion with 5.5 mM glucose (P less than 0.02 0.001). Theophylline (1 mM) also enhanced the overall mean insulin concentration and amplitude (69.4 +/- 10.4 and 14.2 +/- 1.2 microU/ml, respectively) compared with control studies without theophylline (16.7 +/- 5.3 and 4.3 +/- 0.5 microU/ml) (P less than 0.01). The period of the cycle was also increased from 17.5 +/- 1.1 to 26.4 +/- 6.3 min, but this was not significantly different from the control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210054 TI - Structure of cat islet amyloid polypeptide and identification of amino acid residues of potential significance for islet amyloid formation. AB - Cats and humans, unlike most rodent species, develop amyloid in the islets of Langerhans in conjunction with non-insulin-dependent diabetes mellitus. The amyloid consists of a 37-amino acid polypeptide referred to as islet amyloid polypeptide (IAPP). The primary structures of IAPP from human and three rodent species have previously been determined. Sequence divergence was seen in the region corresponding to amino acid residues 20-29, which in human IAPP has been suggested to confer the amyloidogenic properties to the molecule. Using polymerase chain-reaction methodology, we determined the primary sequence of cat IAPP. Amino acid region 20-29 shows specific similarities and differences compared with human and rodent IAPP, respectively. A synthetic cat IAPP20-29 decapeptide formed amyloid fibrils spontaneously in vitro. Comparison between the structure and amyloid fibril-forming activity of various synthetic peptides suggests that the amino acid residues at positions 25-26 in mature IAPP are important for the amyloidogenic properties of the molecule. PMID- 2210056 TI - Immediate elimination of labile HbA1c with allosteric effectors of hemoglobin. AB - Our aim was to find a simple method of removing labile glycosylated hemoglobin (HbA1c) from blood samples before it is measured by cation-exchange chromatography. Labile HbA1c is formed by the binding of glucose to the NH2 terminal valine of the beta-chain of HbA. We sought a more competitive binder for the same site to dissociate labile HbA1c to glucose and HbA. Inorganic phosphates were found to have a strong allosteric effect and a great ability to eliminate labile HbA1c. We developed our method with 4 mM tetrapolyphosphate in the hemolyzing solution to eliminate labile HbA1c during the automatic processing (at pH 6 and heated for 2 min at 45 degrees C) of blood samples for HbA1c estimation. This may be useful when estimating HbA1c by the manual method. PMID- 2210055 TI - Human insulin-receptor gene. Partial sequence and amplification of exons by polymerase chain reaction. AB - The partial sequence of the human insulin-receptor (hINSR) gene is presented. Using the gene sequence as a guide, we selected pairs of oligonucleotide primers from sites in the introns that flank each exon. These primers allowed each of the 22 exons of the hINSR gene to be amplified in vitro by the polymerase chain reaction. The sequences of the gene and oligonucleotide primers will facilitate studies of genetic variation in the hINSR gene and thereby increase our understanding of the role of this gene in the development of insulin-resistant states and glucose intolerance. PMID- 2210057 TI - Effect of hyperinsulinemia and hyperglycemia on intracellular glucose and fat metabolism in healthy subjects. AB - Hyperinsulinemia and hyperglycemia per se both stimulate glucose uptake and the disposal of glucose by oxidative (Gox) and nonoxidative (Nox) metabolism. However, the intracellular metabolic fate of glucose may not be the same when glucose uptake is stimulated predominantly by either of these mechanisms due to different effects on fat oxidation (Fox). To address this issue, 11 healthy subjects each had four glucose-clamp studies performed in combination with indirect calorimetry to compare Gox, Nox, and Fox at two different rates of glucose uptake (approximately 7 and 10 mg.kg-1 fat-free mass [FFM].min-1) matched at each level by either hyperglycemia or hyperinsulinemia. When glucose uptake was matched at the lower rate (7 mg.kg-1 FFM.min-1), there was less suppression of both FFA (33 vs. 43%, P less than 0.05) and Fox (73 vs. 90%, P less than 0.05) and less stimulation of incremental (above basal) Gox (1.95 vs. 2.49 mg.kg-1 FFM.min-1, P less than 0.025) at low insulin (72 pM) and hyperglycemia (21.8 mM) compared with high insulin (280 pM) and euglycemia (5.1 mM). Matching glucose uptake at the higher rates (10 mg.kg-1 FFM.min-1) required greater than 300 pM of insulin (309 and 632 pM) in both studies and resulted in maximal suppression of FFA (49 vs. 46%, NS) and Fox (both greater than 90%, NS) and similar incremental Gox (2.89 vs. 2.73 mg.kg-1 FFM.min-1, NS) whether at hyperglycemia (15.7 mM) or euglycemia (5.2 mM). Therefore, both hyperinsulinemia and hyperglycemia stimulate glucose uptake and increase intracellular glucose availability, but insulin also regulates Gox by suppression of FFA and Fox. However, when FFA and Fox are maximally suppressed, the rate of glucose uptake, rather than the prevailing insulin level, determines the distribution of intracellular glucose metabolism. PMID- 2210058 TI - Occurrence of type VI collagen in extracellular matrix of renal glomeruli and its increase in diabetes. AB - Human and bovine glomerular basement membrane (GBM) preparations, representing the extracellular matrix of the renal filtration units, were found to contain type VI collagen. This protein was solubilized by guanidine and guanidine dithiothreitol extractions and characterized after polyacrylamide gel electrophoretic resolution by immunoblotting with an antiserum directed against the alpha 1(VI) and alpha 2(VI) polypeptide chains and by its insensitivity to collagenase digestion in the nonreduced state. In contrast to GBM, which is the product of three distinct cells, type VI collagen could not be detected in extracts from calf lens capsule, an epithelial cell-derived basement membrane. Quantitation by radioimmunoassay of the type VI collagen content of GBM from 17 diabetic and 15 nondiabetic human subjects indicated a 2.8-fold higher level (P less than 0.001) in the diabetic preparations. Because in the glomerulus type VI collagen is considered on the basis of immunohistochemistry to be localized to the mesangium, we believe that measurement of this protein in GBM preparations can provide a valuable index of mesangial expansion in diabetic and other glomerulopathies. PMID- 2210059 TI - Leucine metabolism in IDDM. Role of insulin and substrate availability. AB - The effect of insulin on plasma amino acid concentrations and leucine metabolism was examined in 18 healthy nondiabetic young volunteers and in 7 subjects with insulin-dependent diabetes mellitus (IDDM) with the euglycemic insulin-clamp technique (40 mU.m-2.min-1) in combination with [1-14C]leucine. All diabetic subjects were studied while in poor metabolic control (fasting glucose 13.3 +/- 1.1 mM; HbA1c 10.8 +/- 0.2%) and again after 2 mo of intensified insulin therapy (fasting glucose 7.2 +/- 0.5 mM; HbA1c 8.0 +/- 0.2%). Insulin-mediated total-body glucose uptake in poorly controlled diabetic subjects (3.6 +/- 0.5 mg.kg-1.min-1) was significantly reduced compared with control subjects (7.5 +/- 0.2 mg.kg-1.min 1; P less than .001) and improved slightly after insulin therapy (4.8 +/- 0.3 mg.kg-1.min-1; P less than .05), although it still remained significantly lower than in control subjects (P less than .01). During the insulin-clamp study performed in subjects with poorly controlled IDDM, endogenous leucine flux (ELF), leucine oxidation (LO), and nonoxidative leucine disposal (NOLD) all decreased (50.1 +/- 2.0 to 26.4 +/- 0.4; 9.2 +/- 0.4 to 6.0 +/- 0.3; 40.9 +/- 2.0 to 20.4 +/- 2.0 mumol.m-2.min-1, respectively) to the same extent as in control subjects. After 2 mo of intensified insulin therapy, the effect of acute hyperinsulinemia on ELF, LO, and NOLD was comparable to that of control subjects, whereas insulin stimulated glucose metabolism was still impaired. To examine the effect of substrate availability on leucine turnover, well-regulated IDDM and control subjects underwent a repeat insulin-clamp study combined with a balanced amino acid infusion designed to increase circulating plasma amino acid levels approximately twofold. Under these conditions, NOLD was equally enhanced above baseline in both control and IDDM subjects (P less than .01), whereas ELF was inhibited to a greater extent (P less than .01) than during the insulin clamp performed without amino acid infusion (control vs. diabetic subjects, NS). In conclusion, insulin-mediated glucose metabolism is severely impaired in subjects with both poorly controlled and well-controlled IDDM, whereas the effect of acute insulin infusion on leucine turnover is normal, and combined hyperaminoacidemia/hyperinsulinemia stimulated NOLD to a similar extent in both IDDM and control subjects. PMID- 2210060 TI - Absence of brown product FFI in nondiabetic and diabetic rat collagen. AB - Accumulation of brown products in long-lived proteins might be an important factor in determining long-term diabetic complications. Fluorescent chromophore 2 (2-furoyl)-4-(5)-(2-furanyl)-1H-imidazole (FFI), isolated from hydrolyzed brown products synthesized in vitro, was proposed as a specific brown product responsible for functional and structural changes in long-lived proteins. In this study, an attempt was made to demonstrate by means of collision spectroscopy the presence of FFI in collagen samples taken from diabetic rats. Diabetic rat collagen samples showed mean values of absorbance per milligram of 4-hydroxy-L proline significantly higher than those observed in nondiabetic rats, suggesting higher FFI levels. Surprisingly, all collagen samples from diabetic and nondiabetic rats gave collision spectra in which no peak diagnostic of FFI presence was observed. These data suggest that the absorbance level observed in diabetic rats is not due to the presence of FFI but to structurally related compounds, which are being investigated by means of mass spectrometry. PMID- 2210061 TI - Family of glucose-transporter genes. Implications for glucose homeostasis and diabetes. AB - Glucose transport by facilitated diffusion is mediated by a family of tissue specific membrane glycoproteins. At least four members of this gene family have been identified by cDNA cloning. The HepG2-type transporter is the most widely distributed of these proteins. It provides many cells with their basal glucose requirement for ATP production and the biosynthesis of sugar-containing macromolecules. The liver-type transporter is expressed in tissues from which a net release of glucose can occur and in beta-cells of pancreatic islets. A genetic defect resulting in reduced activity of this transporter could hypothetically lead to the two principal features of non-insulin-dependent diabetes mellitus, insulin resistance and relative hypoinsulinemia. The adipocyte/muscle transporter is expressed exclusively in tissues that are insulin sensitive with respect to glucose uptake. This protein is an excellent candidate for a highly specific genetic defect predisposing to insulin resistance. PMID- 2210062 TI - Adenosine reversal of in vivo hepatic responsiveness to insulin. AB - Modulation by adenosine of hepatic responsiveness to insulin was investigated in vivo in 10 healthy mongrel dogs of both sexes by determining net hepatic glucose output (NHGO) in response to insulin during the presence or absence of exogenous adenosine infusion. In addition, two separate series of experiments were performed to study the effect of adenosine (n = 7) or glucagon (n = 5) on NHGO. Basal NHGO, quantitated via the Fick principle, was significantly decreased by insulin infusion (4 U/min; 4.8 +/- 0.6 vs. -1.7 +/- 2.6 mg.kg-1.min-1, P less than 0.05). The addition of an intrahepatic arterial infusion of adenosine (10 mumol/min) during insulin infusion caused glucose output to return to basal levels (insulin, -1.7 +/- 2.6 mg.kg-1.min-1; insulin + adenosine, 3.8 +/- 1.6 mg.kg-1.min-1, P less than 0.05). The addition of intrahepatic arterial saline (control) during insulin infusion had no effect on insulin's action (insulin, 1.0 +/- 1.9 mg.kg-1.min-1; insulin + saline, -1.2 +/- 1.6 mg.kg-1.min-1, P greater than 0.05). Hepatic glucose, lactate, and oxygen deliveries were not affected during either insulin or insulin plus adenosine infusion. Intrahepatic arterial infusion of adenosine alone had no effect on NHGO, whereas intrahepatic arterial infusion of glucagon alone stimulated glucose output approximately fivefold (basal, 2.7 +/- 0.4 mg.kg-1.min-1; glucagon, 15.5 +/- 1.2 mg.kg-1.min-1, P less than 0.01). These results show that adenosine completely reversed the inhibition by insulin of NHGO. These data suggest that adenosine may act as a modulator of insulin action on the liver. PMID- 2210063 TI - Islet cell thymidine kinase activity as indicator of islet cell proliferation in rat pancreas. AB - The activity of thymidine kinase (TK;EC 2.7.1.21) in homogenates of isolated rat islets of Langerhans was measured and correlated with the DNA replicatory activity of the islet cells. Adult and fetal rat islets were cultured in medium with 2.7 or 16.7 mM glucose or 16.7 mM glucose and 1 microgram/ml human growth hormone. In both types of islets, 16.7 mM glucose doubled [3H]thymidine incorporation compared with 2.7 mM glucose, and the addition of growth hormone caused a further increase in DNA replication. TK activity in the islets showed similar changes in response to glucose and growth hormone. The correlation between [3H]thymidine incorporation and TK activity was thus highly significant. Cell-cycle analysis of cultured fetal rat islets showed that TK activity was preferentially expressed during the S phase of the cell cycle. TK activity of freshly isolated islets declined with the age of the animal. In pancreatic sections, the islet cell autoradiographic labeling index after [3H]thymidine administration in vivo likewise declined with age and was correlated with the TK activity in freshly isolated islets. It is suggested that measurements of islet TK activity can be used as index of islet cell proliferation; this method has the distinct advantage of avoiding the cumbersome procedure of preparing and scoring autoradiograms. PMID- 2210064 TI - Effect of cyclosporin on generalized Shwartzman reaction in diabetic rats. AB - The effect of cyclosporin (CsA) on the endotoxin-induced generalized Shwartzman reaction (GSR) was studied in diabetic and nondiabetic rats. After 4.5 wk of diabetes, CsA (20 mg/kg) or intralipid as a control substance was given intraperitoneally daily for 10 days. Next, diabetic rats were given either high dose (2 mg/kg or low-dose (0.1 mg/kg) endotoxin (Escherichia coli 026:B6 lipopolysaccharide B) as a single injection. The rats were killed at intervals of 1, 4, 8, and 24 h. No significant glomerular thrombi were seen in the nondiabetic control animals, whereas the severity of glomerular thrombi in the diabetic animals was dependent on the presence or absence of CsA, endotoxin dose, and degree of glycemic control. In the diabetic rats, glomerular thrombi occurred maximally at 4 h but were no longer present at 24 h. The CsA/high-dose-endotoxin rats had fewer glomerular thrombi than rats receiving the intralipid/high-dose endotoxin, but this difference was not statistically significant. The CsA/low dose-endotoxin rats had increased glomerular thrombi compared with the intralipid/low-dose-endotoxin rats (P less than 0.01). Insulin treatment reduced the glomerular capillary thrombi in the CsA/low-dose-endotoxin diabetic animals. Thus, CsA aggravates the GSR with low-dose endotoxin but has no significant effect when high-dose endotoxin is given. Improved glycemic control reduces the GSR in CsA-treated rats. Thus, the interrelationships of diabetes, endotoxin, and CsA on the GSR are complex, and the pathogenesis of these events is unclear. PMID- 2210065 TI - Interaction between insulin and glucose-delivery route in regulation of net hepatic glucose uptake in conscious dogs. AB - In the presence of fixed basal levels of insulin, the route of intravenous glucose delivery (protal vs. peripheral) determines whether net hepatic glucose uptake (NHGU) occurs. Our aims were to determine if the route of intravenous glucose delivery also plays a role in regulating NHGU in the presence of hyperinsulinemia and to determine if length of fast (18 vs. 36 h) influences regulation of NHGU. Five conscious dogs fasted 18 h were given somatostatin and replacement insulin (245 +/- 34 microU.kg-1.min-1) and glucagon (0.65 ng.kg-1.min 1) infusions intraportally. After a 40-min control period, the insulin infusion rate was increased fourfold, and glucose was infused for 3 h. Glucose was given either through a peripheral vein or the portal vein for 90 min to double the glucose load reaching the liver. The order of infusions was randomized. NHGU was measured with the arterial - venous difference technique. Insulin and glucagon levels were 12 +/- 2, 35 +/- 6, and 36 +/- 5 microU/ml and 55 +/- 12, 61 +/- 13, and 59 +/- 7 pg/ml during the control, peripheral, and portal infusions, respectively. The glucose infusion rate, the load of glucose reaching the liver, and the arterial-portal plasma glucose gradient were 0, 9.58 +/- 2.28, and 10.44 +/- 2.94 mg.kg-1.min-1; 29.4 +/- 3.6, 56.8 +/- 3.4, and 56.8 +/- 2.8 mg.kg-1.min 1; and 2 +/- 1, 5 +/- 1, and -51 +/- 15 mg/dl during the same periods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210066 TI - HLA-DQ beta sequence polymorphism and genetic susceptibility to IDDM. AB - The analysis of HLA-DQ beta nucleotide sequence polymorphism in insulin-dependent diabetes mellitus (IDDM) patients and control subjects suggests a role for the DQ beta-chain in genetic susceptibility. Sequence determination and oligonucleotide hybridization was carried out on enzymatically amplified DNA from various HLA-DR typed individuals, including the rare class of DR2+ patients. In the analysis of DQ beta variation in DR4, DRw6, and DR2 haplotypes, a correlation was observed between the presence of the negatively charged residue Asp at position 57 and low susceptibility and the presence of an Ala (DR4), Val (DRw6), or Ser (DR2) and higher susceptibility. However, important exceptions to this pattern have been identified in the analysis of heterozygous DR1/4 IDDM patients. In these individuals, susceptibility appears to correlate with specific DR beta l alleles (Dw4) on the DR4 haplotype, rather than with the DQ beta allele (DQB3.2) that contains Ala at position 57. The DQ beta alleles found in some Chinese IDDM patients also proved discordant with the position-57 correlations. Thus, although there is a general correlation between the residue at position 57 of the DQ beta chain and IDDM susceptibility, these data do not support the notion that Asp 57 confers complete resistance or protection to IDDM. In general, these results suggest that IDDM susceptibility is conferred by specific combinations of DQ beta and DR beta sequences. PMID- 2210068 TI - Differences in lipoprotein subfraction composition and distribution between type I diabetic men and control subjects. AB - Subfractions of very-low-density and low-density lipoproteins were examined in 10 male normolipidemic type I (insulin-dependent) diabetic patients before and after improvement of metabolic control and were compared with subfractions from male control subjects matched to the diabetic patients at entry for age, body mass index, plasma cholesterol, and plasma triglycerides. Two consistent differences in subfraction composition were noted between the diabetic patients at entry and the control subjects. First, subfractions from diabetic patients tended to be cholesterol-ester poor and triglyceride rich; this was particularly marked for the low-density lipoprotein subfractions. Second, the subfractions from pretreatment diabetic patients contained higher proportions of non-apolipoprotein B apolipoproteins. This compositional anomaly, but not the lipid modifications, responded to but was not completely normalized by improved glycemic control, which was also accompanied by reductions in the plasma concentrations of all subfractions. Treatment modified subfraction distribution so that the lipoprotein profile of posttreatment diabetic patients more closely resembled the profile observed in the control subjects. These changes were achieved without significant modification of daily insulin dose. In the context of blood lipid risk factors, the results argue for the need to maintain optimal insulinization even in apparently normolipidemic diabetic patients to avoid modifications of the lipoprotein pattern toward a potentially more atherogenic profile. PMID- 2210067 TI - A unified hypothesis for the complex genetics of HLA associations with IDDM. AB - Our understanding of the role of HLA genes associated with insulin-dependent diabetes mellitus (IDDM) is in disarray, despite recent improvements in the definition of specific alleles and haplotypes. Some genes are highly associated with IDDM, other genes are associated with resistance to IDDM, and some highly associated susceptibility genes are markedly influenced by trans-associated synergistic effects (DR3/4 heterozygotes) or protective effects (DR2/4 heterozygotes). This plethora of genetic associations has spawned the notion that there are many contributing susceptibility genes, which, in turn, has led to the search for shared structural features among different genes on IDDM-associated haplotypes. From a more mechanistic point of view, however, the wide range of variable IDDM associations, with both cis- and trans-encoded protective and/or synergistic effects, suggests a different approach. This article proposes a hypothesis in which the different HLA associations with IDDM can be simply explained by a single unifying concept: a hierarchy of affinities determines the interaction between a diabetogenic peptide and different class II molecules, and an individual is susceptible to IDDM if the class II molecule in that individual with the highest affinity for such a peptide is a DQ beta susceptibility gene. The explicit formulation of this proposal and its genetic implications provide an explanation for HLA-encoded dominant "protection" and for some of the more subtle genetic observations related to cis and trans influences in IDDM susceptibility. PMID- 2210069 TI - Increased preproinsulin mRNA in pancreatic islets incubated with islet cell stimulating antibodies from serums of type I diabetic patients. AB - We recently described autoantibodies that stimulate the release of insulin from pancreatic beta-cells both in vitro and in vivo. The aim of this study was to establish whether islet cell-stimulating antibodies (ICSTAs) also increase islet cell preproinsulin mRNA content. Wistar rat islets, isolated by collagenase digestion, were exposed to 2.7 and 11.1 mM glucose. Insulin release increased 10 fold in response to the higher glucose concentration, and dot-blot analysis of islet mRNA with a rat preproinsulin cDNA probe showed a concomitant increase in mRNA levels. The globulin fractions of four test serums, three from patients with type I (insulin-dependent) diabetes and one from a patient with the insulin autoimmune syndrome, showed clear (5- to 8-fold) stimulation of insulin release. The nonglobulin fractions of these serums and both fractions of three control serums failed to stimulate secretion of insulin. The insulin mRNA content of islets incubated with the ICSTA globulin fractions was greatly increased compared with levels observed in islets treated with control serum globulin fractions. We conclude that ICSTAs not only can stimulate the release of insulin but also increase the preproinsulin mRNA content of islet cells. PMID- 2210070 TI - Participation of glucokinase inactivation in inhibition of glucose-induced insulin secretion by 2-cyclohexen-1-one. AB - We assessed our speculation that 2-cyclohexen-1-one (CHX) impairs glucose-induced insulin secretion through inactivation of glucokinase. Treatment of pancreatic islets with CHX at concentrations (0-5 mM) that caused a dose-dependent inactivation of glucokinase activity similarly inhibited glucose-induced insulin secretion. Another glucose-phosphorylating enzyme (hexokinase) in pancreatic islets was little affected by CHX. CHX-induced inactivation of glucokinase was blocked by the presence of its substrates (glucose and mannose) and an inhibitor (N-acetylglucosamine), all of which also protected against the inhibitory effect of the drug on glucose-induced insulin secretion. CHX also impaired insulin secretion induced by D-glyceraldehyde and dimethyl succinate, which are believed to stimulate the release of the hormone by being directly oxidized by glyceraldehyde-3-phosphate dehydrogenase, by entering the midstream of the glycolytic pathway as glyceraldehyde 3-phosphate, or by entering the tricarboxylic acid cycle in mitochondria after intracellular hydrolysis. The inhibitory effect of CHX on glucose-induced insulin secretion, however, was far more marked than that on insulin secretion evoked by D-glyceraldehyde and dimethyl succinate at any CHX concentrations used. Our study revealed that the inhibitory action of CHX on glucose-induced insulin secretion is exerted mainly, but not solely, through inactivation of glucokinase. This conclusion supports the view that glucokinase is a key enzyme in the recognition of glucose as an insulin secretagogue in pancreatic islets. PMID- 2210071 TI - Heart-rate variability and cardiac autonomic function in diabetes. AB - Cardiac autonomic function was measured in 25 subjects with insulin-dependent diabetes mellitus and 11 control subjects. Autonomic integrity was assessed with standard tests of autonomic function and a new technique of measuring heart-rate variability (HRV) for 24 h. All of the diabetic subjects were selected on the basis of peripheral or autonomic neuropathy or long-term poorly controlled diabetes. They were divided into groups according to presence or absence of vagal neuropathy based on the results of standard tests of autonomic function. Thirteen diabetic subjects had normal autonomic function tests (group 1), and vagal neuropathy was detected in 12 diabetic subjects (group 2). All subjects were monitored by ambulatory electrocardiograph, and the recordings were played back through an analyzer that identified and timed successive pulse (R-R) intervals. HRV was measured from the standard deviation of the successive differences between R-R intervals. HRV was significantly reduced in group 1 (mean +/- SE 73 +/- 9 ms) and group 2 (65 +/- 12 ms) diabetic subjects compared with the control group (138 +/- 10 ms). The standard tests of autonomic function did not distinguish the vagal dysfunction noted with HRV monitoring in group 1 diabetic subjects compared with control subjects. Measurement of 24-h HRV can detect small changes in cardiac autonomic function compared with currently available tests. PMID- 2210072 TI - Compensation by fetal erythrocytes of plasma glucose changes in rats. AB - Changes in plasma glucose and glucose and glycogen content in fetal erythrocytes (FRBCs) were studied in rats between days 15 and 21 of gestation and in adult rats. Plasma and FRBC glucose concentrations increased during fetal life and were higher in erythrocytes than in plasma. Glycogen was higher in FRBCs than in adult erythrocytes and tended to decrease from day 15 to 19 of gestation and to increase again on day 21. When FRBCs were incubated in vitro in different glucose concentrations to study their capacity to compensate for changes in plasma glucose concentration, younger cells showed better glucose-buffering capacities. Glucose and glycogen levels in FRBCs increased when they were incubated in high glucose medium, and the glycogen concentration reached was higher in the early fetal stage than by the end of gestation. Nevertheless, adult erythrocytes accumulated more glycogen in high-glucose medium than cells from any of the fetal aged erythrocytes. When glucose was injected intraperitoneally into fetuses of different ages, there was an increase of 3.7 microM/ml in glucose concentration in blood from the umbilical artery and 2.5 microM/ml in blood from the umbilical vein. FRBCs buffered some of this change, as evident by an increase in glycogen content. Again, buffering capacity was greater for erythrocytes in younger fetuses. Epinephrine diminished glycogen concentration in venous FRBCs on days 19 and 21 of gestation even in hyperglycemia. Insulin diminished glucose concentration in arterial plasma on days 17 and 21 of gestation, but there were no changes in glucose and glycogen in FRBCs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210073 TI - Increased transcapillary escape rate of albumin in nondiabetic men in response to hyperinsulinemia. AB - Diabetic patients manifest increased vascular permeability. To determine whether insulin per se might increase vascular permeability, five nondiabetic men were studied by the hyperinsulinemic-euglycemic clamp technique. Each subject received a 0.72-nmol/kg body wt i.v. insulin bolus, followed by a 72-pmol.kg-1.min-1 insulin infusion for 4 h. Euglycemia was maintained by the Biostator glucose controller. At 7 h of study, 10 microCi i.v. 125I-labeled albumin was injected as bolus dose. Frequent blood samples were drawn during the next 70 min for determination of the transcapillary escape rate (TER) of albumin. Subjects returned 1-2 wk later for a control study, during which 0.45% saline was infused at a rate identical to the dextrose and insulin infusion rates during the hyperinsulinemic clamp. The mean +/- SE serum insulin levels during the hyperinsulinemic clamp and saline infusion were 9786 +/- 126 and 46 +/- 4 pM, respectively, whereas serum glucose during the two sessions was similar (5.0 +/- 0.2 vs. 4.8 +/- 0.1 mM, NS). Identical fluid volumes were infused during the two sessions (1767 +/- 197 ml/7 h), and urine outputs did not differ significantly (1615 +/- 309 vs. 1035 +/- 248 ml/7 h). The TER of albumin was greater in all five men after hyperinsulinemia than after saline infusion (18.3 +/- 2.7 vs. -2.8 +/- 2.3%/h, P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210075 TI - Evidence that downregulation of hexose transport limits intracellular glucose in 3T3-L1 fibroblasts. AB - Measurements of initial glucose entry rate and intracellular glucose concentration in cultured cells are difficult because of rapid transport relative to intracellular volume and a substantial extracellular space from which glucose cannot be completely removed by quick exchanges of medium. In 3T3-L1 cells, we obtained good estimates of initial entry of [14C]methylglucose and D-[14C]glucose with 1) L-[3H]glucose as an extracellular marker together with the [14C]glucose or [14C]methylglucose in the substrate mixture, 2) sampling times as short as 2 s, 3) ice-cold phloretin-containing medium to stop uptake and rinse away the extracellular label, and 4) nonlinear regression of time courses. Methylglucose equilibrated in two phases--the first with a half-time of 1.7 s and the second with a half-time of 23 s; it eventually equilibrated in an intracellular space of 8 microliters/mg protein. Entry of glucose remained almost linear for 10 s, making its transport kinetics easier to study (Km = 5.7 mM, Vmax = 590 nmol.s 1.ml-1 cell water). Steady-state intracellular glucose concentration was 75-90% of extracellular glucose concentration. Cells grown in a high-glucose medium (24 mM) exhibited a 67% reduction of glucose-transport activity and a 50% reduction of steady-state ratio of intracellular glucose to extracellular glucose. PMID- 2210074 TI - Actions of novel antidiabetic agent englitazone in hyperglycemic hyperinsulinemic ob/ob mice. AB - The effects of CP 68722 (racemic englitazone) were examined in ob/ob mice, in adipocytes and soleus muscles from ob/ob mice, and in 3T3-L1 adipocytes. Administration of englitazone at 5-50 mg.kg-1.day-1 lowered plasma glucose and insulin dose dependently without producing frank hypoglycemia in either the diabetic or nondiabetic lean animals. The glucose-lowering effect in ob/ob mice preceded the reduction in hyperinsulinemia. On cessation of drug, plasma insulin returned to untreated levels within 48 h, whereas plasma glucose rose slowly over 5 days. Englitazone (50 mg/kg) for 11 days lowered plasma glucose (22.2 +/- 1.4 to 14.0 +/- 1.9 mM), insulin (7.57 +/- 0.67 to 1.64 +/- 0.60 nM), nonesterified fatty acids (1813 +/- 86 to 914 +/- 88 microM), glycerol (9.20 +/- 0.98 to 4.94 +/- 0.03 mM), triglycerides (1.99 +/- 0.25 to 1.03 +/- 0.11 g/L), and cholesterol (6.27 +/- 0.96 to 3.87 +/- 0.57 mM), but no effects were observed 3 h after a single dose. Basal and insulin-stimulated lipogenesis were enhanced in adipocytes from ob/ob mice treated with 50 mg/kg englitazone for 11 days compared with lipogenesis in cells from vehicle-treated controls. Treatment of ob/ob mice with 50 mg/kg englitazone reversed the defects in insulin-stimulated glycolysis (from [3-3H]glucose) and glycogenesis and basal glucose oxidation (from [1-14C]glucose) in isolated soleus muscles. Englitazone (30 microM) stimulated 2-deoxy-D-glucose transport in 3T3-L1 adipocytes from 0.37 +/- 0.03 to 0.65 +/- 0.06 and 1.53 nmol.min-1.mg-1 protein at 24 and 48 h, respectively. Thus, englitazone has 1) insulinomimetic and insulin-enhancing actions in vitro and 2) glucose-, insulin-, triglyceride-, and cholesterol-lowering properties in an animal model of non insulin-dependent diabetes mellitus (NIDDM) in which sulfonylureas have little or no effect. Thus, this new agent may have beneficial effects including a reduced risk of hypoglycemia in patients with NIDDM. PMID- 2210076 TI - Physiological and pharmacological stimulation of pancreatic islet hormone secretion in type I diabetic pancreas allograft recipients. AB - Successful heterotopic and denervated pancreas allograft transplantation (PAT) often results in normoglycemia and peripheral hyperinsulinemia in insulin dependent (type I) diabetic recipients. The contribution of altered hepatic insulin extraction (HIE) to the resulting hyperinsulinemia in such patients remains uncertain. Furthermore, whether the denervated pancreas allografts exhibit beta-cell hyperresponsiveness to physiological and pharmacological stimulation is controversial. We evaluated beta-cell function and HIE after successful whole cadaveric PAT with systemic venous drainage in 13 type I diabetic patients before and after mixed-meal and intravenous glucose and glucagon administration. The results were compared with those of 5 nondiabetic patients with kidney transplantation only, who had native innervated pancreases with portal insulin delivery and were receiving an equivalent triple immunosuppressive therapy (cyclosporin, azathioprine, and prednisone), and 7 healthy control subjects with no family history of diabetes. After PAT, fasting and poststimulation serum glucose concentrations were normalized. PAT was associated with marked basal hyperinsulinemia (3- to 8-fold) as assessed by immunoreactive insulin (IRI) levels in type I diabetic patients (mean +/- SE 345 +/- 43 pM) compared with control subjects (43 +/- 14 pM) and nondiabetic kidney transplantation patients (129 +/- 38 pM). After mixed-meal ingestion, the mean incremental integrated insulin area was similar in PAT patients (18 +/- 3 nM.min) compared with kidney-transplantation patients (20 +/- 4 nM.min) and healthy control subjects (21 +/- 3 nM.min). Basal serum C-peptide levels were significantly greater in PAT (1.72 +/- 0.13 nM) and kidney-transplantation (2.15 +/- 0.33 nM) patients than in healthy control subjects (0.50 +/- 0.10 nM; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210078 TI - Limited duration of remission of insulin dependency in children with recent overt type I diabetes treated with low-dose cyclosporin. AB - Preliminary data from our group indicated that cyclosporin A induced frequent remissions of insulin dependency in a group of 40 insulin-dependent (type I) diabetic children if given at the onset of clinical manifestations of diabetes. We report a 2-yr analysis of the response to cyclosporin A in the group of 81 patients included in the initial study. As observed before, a remission could be obtained in most of the patients (65%) in association with a shorter duration of symptoms, less severe hyperglycemia, lower incidence of ketoacidosis, and higher plasma C-peptide concentrations. All remissions ended during the follow-up period after a mean +/- SE duration of 316 +/- 21 days (range 31-850 days). Two parameters were linked to the duration of remissions: the mean circulating level of cyclosporin during the first 3 mo and the duration of prediagnostic polyuria. We were unable to relate the end of a remission to variations in the cyclosporin regimen, titer of autoantibodies, or progression of beta-cell failure. The euglycemic clamp technique revealed that insulin sensitivity decreases with time in patients not taking insulin. At 24 mo, the patients who had a remission of insulin dependency had better glycemic control, lower insulin dosages, and C peptide levels two- to threefold higher than the nonremission patients and four- to sixfold higher than the historical control subjects. The cyclosporin regimen was well tolerated over the observed period: more specifically, serum creatinine remained unchanged, and kidney biopsies performed at 18-24 mo of treatment were within normal limits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210077 TI - Insulinomimetic properties of trace elements and characterization of their in vivo mode of action. AB - Lithium and vanadate have insulinomimetic actions in vitro. In this study, we examined the in vivo effects of lithium and vanadate on glucose metabolism in diabetic (90% partial pancreatectomy) rats. Four groups of chronically catheterized rats were studied: control, diabetic, diabetic treated with lithium (plasma concn 1.0 +/- 0.1 meq/L) and vanadate (0.05 mg/ml in drinking water), and diabetic treated with lithium, vanadate, zinc, and magnesium. Postmeal plasma glucose was increased in diabetic versus control rats (18.7 vs. 7.7 mM, P less than 0.01) and was normalized by addition of lithium and vanadate (8 mM) or lithium, vanadate, zinc, and magnesium (7.4 mM). Euglycemic insulin-clamp studies were performed 2 wk posttreatment; insulin-mediated glucose uptake was reduced in diabetic compared with control rats (142 +/- 4 vs. 200 +/- 5 mumol.kg-1.min-1, P less than 0.01), returned to normal with lithium and vanadate (206 +/- 6 mumol.kg 1.min-1), or increased to supranormal levels with lithium, vanadate, zinc, and magnesium (238 +/- 6 mumol.kg-1.min-1). During the insulin clamp, muscle glycogenic rate was severely impaired in diabetic versus control rats (18 vs. 70 mumol.kg-1.min-1) and was normalized by lithium and vanadate (91 mumol.kg-1.min 1) or lithium, vanadate, zinc, and magnesium (93 mumol.kg-1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210079 TI - Biochemical studies of RT6 alloantigens in BB/Wor and normal rats. Evidence for intact unexpressed RT6a structural gene in diabetes-prone BB rats. AB - Lymphocytes bearing the T-lymphocyte differentiation antigen RT6 play an important immunoregulatory role in the development of autoimmune diabetes in BB rats. Immunofluorescence studies suggest that diabetes-prone (DP)- but not diabetes-resistant (DR)-BB rat lymphocytes fail to express RT6 antigen during ontogeny. Two alloantigenic forms of the molecule exist, i.e., RT6.1 and RT6.2; both are linked to cell membranes by a phosphatidylinositol (PI) linkage. In these studies, PI-phospholipase C (PLC) treatment of lymphocytes from BB and normal rats followed by immunoabsorption and sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis of released proteins with anti-RT6 allotype-specific monoclonal antibodies was performed. RT6.1 in several nondiabetic rat strains was found to consist of a family of nonglycosylated and variably glycosylated molecules: an N-Glycanase-resistant 24,000- to 26,000-Mr peptide and four N-Glycanase-sensitive peptides of 29,000, 31,000, 33,000, and 34,000 Mr. In contrast, RT6.2 was found to be a 24,000- to 26,000-Mr nonglycosylated polypeptide. The electrophoretic pattern of RT6.1 was observed to be the same when the antigen was extracted from W3/25+ (CD4+) versus W3/25- T lymphocytes or from resting versus mitogen-activated cells. A pattern of bands characteristic of the RT6.1 antigen found in normal rat strains was detected after PLC treatment or detergent solubilization of lymphocytes obtained from DR rats. In contrast, no evidence of either RT6 species was found after PLC or detergent treatment of comparable numbers of T lymphocytes from DP-BB rats. Interestingly, T lymphocytes from Wistar-Furth (RT6.2+) x DP (RT6-) F1 crosses were observed to coexpress both RT6.2 and RT6.1 molecules, with the electrophoretic pattern of RT6.1 being similar to that obtained in DR and other rat strains. This study provides biochemical evidence that DP rats may have an intact RT6a structural gene. PMID- 2210080 TI - Diabetes and the myo-inositol paradox. AB - To test the general applicability of the hypothesis that diabetes mellitus causes increased polyol pathway activity, decreased tissue free myo-inositol, and resultant pathological changes in tissues susceptible to the ravages of diabetes, we measured glucose, sorbitol, and myo-inositol with quantitative histochemical techniques in layers of the cornea, the aortic myointima, the cardiac left ventricle and atrioventricular node (AVN), and retina and kidney after 19 days or 2 mo (mildly diabetic non-insulin-treated [MD] and severely diabetic insulin treated [SD] groups) in the alloxan-induced diabetes model. In the aqueous humor, glucose rose linearly with increased serum glucose, sorbitol was markedly increased in the MD and SD groups, and myo-inositol did not change in any diabetic group. There was no change in glucose or sorbitol in aortic myointima in any group, but myoinositol was decreased in 19-day diabetic rabbits by 26%, unchanged in MD rabbits but paradoxically increased by 60% in SD rabbits. Glucose, sorbitol, and myo-inositol increased in all three corneal layers in SD rabbits but only in epithelium and stroma in 19-day and MD rabbits. AVN glucose and sorbitol did not change in 19-day diabetic, MD, or SD diabetic rabbits. AVN myo-inositol was three times higher than ventricular myo-inositol and did not appear to change in SD rabbits. Retinal pigmented epithelium myo-inositol was decreased 30% in SD rabbits. Glomerular myo-inositol was also decreased, but not significantly, in SD rabbits. We conclude that the paradoxical increase in corneal and aortal myo-inositol raises fundamental questions about the general applicability of the myo-inositol-depletion hypothesis. PMID- 2210082 TI - Development of co-ordination of sucking, swallowing and breathing: ultrasound study of term and preterm infants. AB - Fourteen newborn babies of different gestational ages (33 to 40 weeks) but similar postnatal age (four to 19 days) were studied during bottle-feeding using real-time ultrasonography, combined with respiratory monitoring. Previously undescribed tongue movements and graded changes in the temporal relationships between tongue movements, swallowing and breathing were observed among infants of differing maturity. These were most marked in the least mature infants, but were occasionally seen in term infants. The results suggest that adequate neuromuscular co-ordination is more a function of gestational maturity than of postnatal sucking experience. The pattern of intraoral events for infants of differing maturity described in this study provides a framework for the study of feeding problems of term and preterm infants. PMID- 2210081 TI - Nature and prognosis of seizures in patients with cerebral palsy. AB - The nature, course and prognosis of seizures were investigated in patients with epilepsy and cerebral palsy (CP). 174 children with epilepsy were investigated: 57 with CP and 117 who were otherwise neurologically normal. Epilepsy in patients with CP was characterized by early age at onset, generalized focal and multifocal seizures and a poorer prognosis. The presence of cerebral palsy requires differential consideration of the severity of epilepsies. This may be of appreciable importance for the prognostic evaluation of anticonvulsant therapy or the course of epilepsy. PMID- 2210083 TI - Neurobehavioural development at term of extremely low-birthweight infants (less than 901g). AB - In a population of extremely low-birthweight (ELBW) infants with birthweights from 500 to 900g, born at 24 to 30 weeks gestation, neurobehavioural development at term was evaluated with the Brazelton Neonatal Behaviour Assessment Scale (BNBAS) and a standardized neurological examination. Compared with a control group of fullterm infants, no significant group differences were found for 19 of 27 BNBAS items; in seven other items they scored significantly lower and in one item they scored significantly higher. The BNBAS and the neurological examination showed abnormal responses in most ELBW infants with intracranial haemorrhage, especially those with grades III or IV. In spite of these differences the ELBW infants at term had a wide behavioural repertoire, with repeated, but short, periods of alertness and high performance. Parental awareness of the fluctuating state of ELBW infants at term is important for adequate parent-infant interactions. PMID- 2210084 TI - Life conditions of adolescents with myelomeningocele. AB - Twenty six adolescents with myelomeningocele have been followed from birth: they comprise the whole population born with myelomeningocele between 1964 and 1967 in one Swedish medical district. 18 have severe physical handicaps, and although there are equal numbers of males and females, more females have severe handicaps, 22 of the 26 have been educated in normal schools (19 in normal classes), but learning difficulties are common. Three other adolescent are mildly mentally retarded and one is severely so. Only seven have complete urinary continence. 19 take part in leisure-time activities, but many felt they had poor social contact with their schoolmates and one in three were competent in activities of daily living. In general, self-concept was poor and many had inadequate knowledge about sexuality and the cause of their handicap. Recently established Handicapped Adult Teams have proved important in providing a link between the adolescent and public services dealing with health, education, employment and social services. PMID- 2210086 TI - Sleep in the first year of life. AB - The sleep patterns of 174 infants were recorded on one typical day at six, 13, 26 and 52 weeks of age, using a 24-hour log. During the first year of life the number of episodes of sleep was reduced by about 50 per cent, but total sleep time was reduced by only two hours. A circadian rhythm was established by six weeks of age. Smaller infants slept more than larger ones in the first months of life. Sex or birth-order of the child did not affect the duration or number of sleep episodes, but sleep pattern related significantly to whether or not mothers found their infants difficult to feed. Introduction of weaning food at an early stage reduced the number of sleep episodes, but increased the average length of each episode. Socio-economic status showed no significant relationship with number of episodes or total length of sleep. PMID- 2210085 TI - Diagnostic features and clinical signs of 21 patients with lissencephaly type 1. AB - Lissencephaly type I has been described as either the cerebral expression of a complex malformation syndrome such as Miller-Dieker syndrome (MDS), or as isolated lissencephaly sequence (ILS). In a nation-wide study in The Netherlands, of 21 patients with lissecephaly type I, four were found to have MDS and 17 ILS. New clinical aspects were as follows: the mean life-span of the entire group was longer than previously reported; patients with lissencephaly grades 3 or 4 (mixture of agyria and pachygyria, or complete pachygyria) developed seizures later than those with grades 1 and 2 (complete and almost complete agyria); microcephaly was not always present in patients with grades 3 and 4 lissencephaly; and patients with lissencephaly grades 1 and 2 had hardly any psychomotor development, while those with grades 3 and 4 were severely retarded. PMID- 2210087 TI - Late hydrocephalus after arrest and resolution of neonatal post-hemorrhagic hydrocephalus. AB - This report describes the occurrence of rapid progression of hydrocephalus after discharge from the nursery in four of 48 infants who had had previous arrest of progression of post-hemorrhagic hydrocephalus, and at least partial resolution of ventriculomegaly. This later-onset hydrocephalus occurred at a mean age of seven months; the most consistent presenting clinical feature was rapid head growth. Three of the four infants required a ventriculo-peritoneal shunt and the fourth was treated with acetazolamide, with apparent resolution of the hydrocephalus. Newborn infants with post-hemorrhagic hydrocephalus should be followed carefully throughout the first year for prompt detection of later hydrocephalus. PMID- 2210088 TI - The brain in the 18q-syndrome. AB - The authors describe the cerebral neuropathological findings of a 25 1/2-year-old male with 18q-syndrome. An abnormal gyral pattern, atrophy of the olfactory and optic nerves and small neocerebellar hemispheres with hemispheral lobular sclerosis were noted. Microscopically there were pial glioneuronal heterotopias; misplacement of neurons in the molecular layer of the cortex, as well as in deep white matter; not readily identifiable Betz cells; gliosis of olfactory and optic tracts and elsewhere; and loss of Purkinje cells. Further detailed studies of other cases are needed to determine whether these abnormalities are characteristic of the 18q-syndrome. PMID- 2210090 TI - Is Asperger's a syndrome? PMID- 2210089 TI - Neocerebellar hypoplasia in a neonate following intra-uterine exposure to anticonvulsants. AB - An infant with dysmorphic features was born to an epileptic mother who had taken phenytoin and sodium valproate throughout pregnancy. The infant began to have intractable seizures 10 minutes after delivery, and retrospective reports from the mother suggested they may have occurred in utero. Ultrasound examination of the brain showed a very wide subarachnoid space and CT confirmed cerebral and cerebellar underdevelopment. The infant died at three days of age and autopsy revealed a small brain with neocerebellar hypoplasia. This case might represent an extreme example of anticonvulsant teratogenicity. PMID- 2210091 TI - The role of gastric mucosal histamine in acid secretion and experimentally induced lesions in the rat. AB - The role played by histamine from enterochromaffin-like (ECL) cells and mast cells in gastric acid secretion and in the development of ethanol-induced gastric lesions was studied in the rat. This was done by examining the effects of inhibition of the histamine-producing enzyme histidine decarboxylase (HDC) with alpha-fluoromethylhistidine (alpha-FMH) and the effects of degranulation of the mucosal mast cells with dexamethasone. A single dose of alpha-FMH (50 mg/kg p.o.) inhibited the HDC activity by 94% but did not affect histamine levels in the gastric mucosa 2 h after dose. Repeated treatment resulted in an almost complete inhibition of HDC activity and in a reduction of histamine levels by 75%. Pentagastrin failed to stimulate acid secretion after 4 days treatment with alpha FMH, whereas the acid response to histamine was unaffected in chronic gastric fistula rats. Ethanol failed to induce gastric lesions in rats pretreated for 4 days with dexamethasone whereas 4 days pretreatment with alpha-FMH did not influence ethanol-induced lesion formation. The present results show that histamine synthesis is required for pentagastrin-stimulated gastric acid secretion and that mucosal mast-cell histamine plays a role in the development of ethanol-induced gastric lesions. PMID- 2210092 TI - Occupational mortality of inflammatory bowel disease. AB - A characteristic pattern in the occupational distribution of idiopathic inflammatory bowel disease (IBD) could help to focus research with regard to its etiology or reveal the nature of possible environmental risk factors. The present study analyses occupational mortality from Crohn's disease and ulcerative colitis in England and Wales during 8 consecutive years. Mortality of various occupations was expressed as proportional mortality ratio (PMR) or standardized mortality ratio (SMR). From 1979 to 1986, 321 men aged 16-74 years died from Crohn's disease, and 406 men died from ulcerative colitis. The respective number in women were 561 and 429. In men, there was a correlation between PMR and SMR among various occupations, with r = 0.80 and 0.65 for Crohn's disease and ulcerative colitis, respectively. A relatively low occurrence of male IBD was found in occupations associated with physical work, lower social status, and farming. By contrast, high mortality from IBD tended to be associated with physically less demanding work, sedentary occupations, and type of work which is done indoors. PMID- 2210093 TI - Pancreatic excretion of dimethadione and trimethadione by repeated oral administration of trimethadione in dogs. AB - To examine pancreatic excretion of dimethadione (DMO), a weak organic acid, as well as of its precursor trimethadione (TMO), TMO was given orally to dogs with pancreatic fistulae at a dose of 10-160 mg/kg/day over a period of 14 days. Blood samples were taken once a day during the administration of TMO and for 7 days after discontinuation of the drug. On the 15th day, pancreatic juice was collected under stimulation by secretin (2 Crick-Haper-Raper units/kg/h). DMO concentration in plasma reached a maximal plateau around the 10th day after starting TMO administration, and depended directly on the dose of TMO. Pancreatic excretion of DMO at a steady state closely depended on both the dose of TMO and the DMO concentration in plasma. The pancreatic juice/plasma concentration ratio for DMO exceeded 1.0 at a steady rate and decreased with the increased flow rate. Pancreatic DMO clearance (DMO output/DMO concentration in plasma) increased, depending on the flow rate, the bicarbonate concentration, and pH of pancreatic juice. Pancreatic excretion of TMO was zero or extremely low. PMID- 2210094 TI - Cigarette smoking increases gastric luminal prostaglandin F2 alpha and thromboxane B2 in healthy smokers. AB - Pentagastrin-stimulated gastric luminal prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, PGF2 alpha and thromboxane B2 (TxB2) were measured using a second antibody solid-phase enzyme immunoassay before, during and after cigarette smoking in healthy smokers. Smoking significantly increased PGF2 alpha and TxB2 concentration and output; in contrast no significant changes were found for PGE2 and 6-keto-PGF1 alpha levels. In addition, cigarette smoking caused a significant reduction in gastric juice volume and acid output but did not alter intragastric acidity. These findings may suggest a possible role of prostanoids in the response of the stomach to cigarette smoking. PMID- 2210095 TI - Rat intestinal iron transfer capacity and the longitudinal distribution of its adaptation to iron deficiency. AB - The longitudinal gradient of intestinal iron transfer was investigated in normal and iron-deficient male Sprague-Dawley rats in vitro and in vivo. In normal rats in vitro iron transfer in the duodenum was approximately 3 times higher than in the jejunum and decreased in the ileum to approximately half the jejunal values. Compared to the controls in vitro iron transfer was increased 3-4 times in the duodenum and in the first jejunal segment and 2-3 times in the second jejunal segment. No significant adaptation to iron deficiency was found in the rest of the small intestine. Iron transfer rates showed the same longitudinal pattern when iron was chelated with nitrilotriacetic acid (NTA) or with ascorbate. The absorbed iron quantities, however, were approximately 5 times lower when Fe ascorbate was used, which might be due to differences in bioavailability. Omission of Fe-NTA and Fe-ascorbate had no impact on the vitality of the segments. Glucose transfer was used as vitality criterion. It was not significantly different between corresponding iron-deficient and control segments. To control these results in vivo mesenteric blood was collected from duodenal and jejunal segments in situ. Corresponding to in vitro findings iron transfer was close to linear over the experimental period. In iron deficient duodenal segments iron transfer increased approximately 3 times as compared to controls while no adaptational changes were found in the distal jejunum. No significant longitudinal gradient was found in the mucosal content of ferritin and nonheme iron. Both parameters were decreased in iron deficiency by about half. The mucosal transferrin content showed no longitudinal gradient in control animals. In iron deficiency transferrin was significantly increased in the duodenum and in the three most proximal jejunal segments. The results indicate that in rats adaptation of iron absorption to the demand can only be expected in the duodenum and in the proximal 20 cm of the jejunum. Because this process shows a steep gradient in the proximal small intestine, studies on the adaptation of intestinal iron transfer to the demand should use short and well-defined segments in order to provide reproducible results. PMID- 2210096 TI - Development of a human stomach explant organ culture system to study the pathogenesis of Helicobacter pylori. AB - These studies were undertaken to define conditions under which Helicobacter (formerly Campylobacter) pylori and viable human gastric mucosa could coexist in tissue culture with the ultimate goal of developing an in vitro experimental model which could be used to study interactions between H. pylori and gastric epithelium. Antral gastric biopsies obtained at upper endoscopy were placed in culture in either CMRL-1066 or keratinocyte growth media and incubated at 37 degrees C in either an oxygen-enriched environment (45% O2, 50% N2, 5% CO2) or a standard oxygen environment (95% air, 5% CO2). Without selective antibiotics to suppress growth of non-H.-pylori organisms, H. pylori could not be isolated from most initially positive tissue even after only 2 h in tissue culture; however, when selective antibiotics were utilized in the tissue culture media, H. pylori was isolated from 9 of 14 initially positive cases after 24-72 h in tissue culture. There was little difference in the morphology of either surface or glandular epithelium in H.-pylori-negative explants between time zero and 48-hour cultures. However, H.-pylori-positive explants after 48 h in tissue culture showed a significant increase in injury to both surface and glandular epithelium when compared to time zero specimens. These data demonstrate that viable H. pylori and human gastric epithelium can be maintained in explant organ culture and suggest that this gastric mucosal explant culture system may be useful in studying the significance of H. pylori infection of human gastric epithelia. PMID- 2210097 TI - Jejunal and ileal glucose-stimulated water and sodium absorption in tropical enteropathy: implications for oral rehydration therapy. AB - Intestinal glucose and water absorption in response to glucose has been studied in tropical enteropathy with a view to determine the optimum glucose concentration in oral rehydration solutions for use in the tropics. Maximum jejunal water and sodium absorption occurred from an 80-mM glucose-sodium chloride solution (-285.7 +/- 46.0 ml/30 cm/h and -31.8 +/- 3.8 mM/30 cm/h, respectively) during in vivo steady-state jejunal perfusion. At perfusate glucose concentrations greater than 250 mM, however, jejunal water and sodium secretion occurred. In the ileum, maximum glucose-stimulated water absorption (-91.1 +/- 27.1 ml/30 cm/h) was significantly less than in the jejunum. Glucose absorption demonstrated saturation kinetics in both the jejunum and ileum. The half saturation concentration was higher in the jejunum (167 mM) compared to the ileum (28 mM). This study suggests that the optimal glucose concentration for oral rehydration solutions used in the tropics should be 80 mM, as lower and higher concentrations result in diminished jejunal water absorption. PMID- 2210098 TI - Hearing in the elderly: the Framingham cohort, 1983-1985. Part I. Basic audiometric test results. AB - Many studies have documented the decline in auditory function with age. We broaden that data base in this the first of a series of reports emanating from the auditory testing of the Framingham cohort during biennial exam 18. The results of the auditory questionnaire, hearing sensitivity, acoustic compliance measures, and word recognition tests obtained from 1662 men and women in their 60th through 90th decades are presented. Pure-tone thresholds increased with age but the rate of change with age did not differ by gender even though men had poorer threshold sensitivity. Maximum word recognition ability declined with age more rapidly in men than in women and was poorer in men than in women at all ages. Acoustic compliance and middle ear pressure did not vary with gender or age. Acoustic reflex thresholds to a contralateral stimulus at 1 kHz increased slightly with age, more in women than in men; ipsilateral acoustic reflex thresholds did not vary with age or gender. Hearing aids were being used in only 10% of subjects likely to benefit from amplification. PMID- 2210099 TI - Presbycusis and noise-induced hearing loss. AB - In a longitudinal and an age cohort comparing study the influence of aging and occupational noise exposure on hearing sensitivity was studied. The participants of the longitudinal study were studied at 70, 75, and 79 years of age. Seventy year old men exposed to occupational noise had 10 to 15 dB poorer hearing in the high frequency range than nonexposed men. The difference in hearing acuity decreased with increasing age. The differences between exposed and nonexposed older persons was no longer significant at age 79. In women there were no differences in hearing sensitivity between those exposed to noise and those not exposed to noise. Men not exposed to noise had 10 to 15 dB poorer hearing at 4 kHz compared with women of the same age also not exposed to noise. PMID- 2210100 TI - Speech recognition ability of children with unilateral sensorineural hearing loss as a function of amplification, speech stimuli and listening condition. AB - The purpose of this investigation was to examine three types of audiological recommendations [unaided, CROS (contralateral routing of signals) and personal FM system] and their impact upon speech recognition ability of children with unilateral sensorineural hearing loss. Each of these recommendations was tested under three listening conditions encountered in a classroom [monaural direct (MD), monaural indirect (MI), midline signal/omnidirectional noise (MS/ON)] with two types of speech materials (Nonsense Syllable Test and an American English adaptation on the Bamford-Kowal-Bench Sentence Lists). These experimental conditions were simulated in a classroom, recorded on audiotape, and played back to subjects under headphones to control such factors as signal-to-noise ratio, earmold fit, and head shadow effects. Six school-age children with unilateral hearing losses between 56 and greater than 120 dB HL (PTA) were evaluated using a repeated measures design. The children experienced the most listening difficulty in the MI condition when they were unaided. The CROS aid improved speech recognition in this condition but degraded speech recognition in the MD condition. The FM system was the only audiological recommendation to produce uniformly high speech recognition scores across all listening conditions with both types of speech materials. Implications for the audiological management of unilaterally hearing-impaired children in the classroom are discussed. PMID- 2210101 TI - Bone vibrator placement and the cancellation technique. AB - An issue in the measurement of bone conduction sensitivity is the placement of the bone vibrator. The effect of bone vibrator position on the amplitude and phase of the received signal was investigated using a cancellation technique. This technique involves cancelling the signal delivered by the bone vibrator with a signal delivered acoustically via an earphone. At cancellation, the acoustic signal is equal in amplitude but opposite in phase to the bone-conducted signal. Results showed that the amplitude of the received signal did not vary significantly with bone vibrator position close to the center of the forehead whereas the phase of the received signal was critically dependent on bone vibrator position. Substantial intersubject differences were observed in the variation of phase with bone vibrator position. The precision of measurement using the cancellation technique was found to be high. PMID- 2210102 TI - Tests of the precedence effect in sound localization reveal abnormalities in multiple sclerosis. AB - The precedence effect in sound localization involves presenting identical sounds (e.g., clicks) from pairs of matched speakers situated on opposite sides of a subject's head, with the clicks from one speaker preceding those from the other by a short interval. With appropriate delays, normal subjects perceive a fused image which originates from the side of the leading speaker. This test was administered to 24 patients with multiple sclerosis (MS). Separate tests involving speaker delays ranging from 0 msec (simultaneous presentation) to 8 msec were presented. At 0 msec delay, normal subjects perceived the fused image to be located halfway between the two speakers; at progressively longer delays, the image was perceived closer to the leading speaker. In contrast to normal subjects, a large proportion of the MS subjects exhibited difficulties with the task. The discrimination deficit was limited to delays below 1 msec, suggesting a problem involving an increased threshold for lateralizing the fused image away from midline toward the side of the leading speaker. The neural instability produced by demyelination in MS patients might account for this pattern of results. PMID- 2210103 TI - Loudness and auditory brain stem evoked response. AB - Auditory brain stem responses evoked with click stimuli of varying repetition rates (11, 31, 51, and 91 clicks/sec) and intensities but judged as being equally loud as three reference loudness levels (90, 80, and 70 phons) were examined in normal-hearing listeners. Analysis of wave component latencies and amplitudes indicated that loudness level changes are reflected in the brain stem response. However, the combined influence of stimulus rate and intensity was greater than that of perceived loudness level. It was concluded that the auditory brain stem response does not provide a direct link to loudness perception. PMID- 2210104 TI - The resonance frequency of the external auditory canal in children. AB - The frequency of the resonance peak of the external auditory canal was measured in 250 children aged 3 to 12 years. The mean resonance peak frequency was greatest in the younger age groups (3089 Hz in 4 year olds, range 2298 to 3763) and then decreased with age until 7, the age at which adult values were reached. Children less than 7 years of age have mean resonance frequencies significantly different from adults, suggesting that the "adult" length of external auditory canal is not reached until the age of 7. This alteration in resonance frequency with age may have practical implications by affecting the insertion gain of hearing aid systems in children. PMID- 2210105 TI - Preferred hearing aid gain in everyday use after prescriptive fitting. AB - The insertion gain preferred by a group of 26 moderately hearing-impaired, elderly hearing-aid users was investigated in everyday listening situations. The subjects used monaural behind-the-ear aids, carefully fitted according to a prescription formula of the half-gain type, validated and used at National Acoustic Laboratories, Australia. The fitting was checked with real-ear measurements of insertion gain and reviewed at one or more follow-up sessions. The subjects were strictly instructed to try the recommended volume control setting before reporting which setting they preferred. The prescription significantly over-estimated preferred gain by about 7 dB. No correlation could be detected between prescribed versus preferred gain differences and the amount of previous hearing-aid use or the degree of subjective hearing problems. PMID- 2210106 TI - The effect of probe tube reference placement on sound pressure level variability. AB - This study examined the effect of external microphone reference placement on peak sound pressure level (pSPL) and measurement variability. Nine normal subjects were seated in a double-walled sound suite, 1 m and 0 degrees azimuth from a wall mounted speaker. Digitized Gaussian noise was presented at 80 dB pSPL with a 500 msec duration and was measured through a probe tube microphone assembly. Replicated measurements were made at five locations external to the pinna. They were: anterior-superior and posterior-superior positions simulating hearing aid microphone placement (locations 1 and 2) and 2, 4, and 6 cm lateral to the lateral edge of the pinna (locations 3, 4, and 5). Means, standard deviations, and ranges were compared, and statistical analyses were performed. The highest pSPL values were recorded lateral to the pinna, and the lowest values were obtained at the simulated hearing aid positions. ANOVAs indicated a main effect for pSPL, and post hoc testing demonstrated a significant difference between the posterior-superior and 2 cm lateral to the pinna positions. Variability was largest at the posterior-superior and 6 cm positions, and lowest 2 cm from the pinna. From this study, we concluded that pSPL and variability are both important criteria for selecting an optimal reference microphone site and both can affect the accuracy of ear canal measurements. A reference site 2 cm from the pinna eliminates attenuation of the signal and is the least variable site. PMID- 2210107 TI - Pitch scaling and speech understanding by patients who use the Ineraid cochlear implant. AB - Pitch scaling was assessed for 10 normal-hearing listeners and 8 patients who use the Ineraid multichannel cochlear implant. For two patients who were excellent users of the prosthesis, pitch increased over a wide range of frequencies (100 Hz to 2333-3000 Hz). For three patients who were above average users of the prosthesis, pitch increased with frequency over a smaller range (100 Hz to 1200 2300 Hz). For three patients who demonstrated poor word recognition ability, pitch increased with frequency over a very small range (100 Hz to 600-1000 Hz). These results suggest that differences in speech understanding among patients who use the Ineraid may be accounted for, in part, by the range of pitch available through the implant. PMID- 2210108 TI - An extended care transitional unit. PMID- 2210109 TI - Community care in Britain: a model for Canada. PMID- 2210110 TI - Care giver relief is a vital link. PMID- 2210111 TI - SPECS helps seniors in Labrador. PMID- 2210112 TI - The elderly in acute care: a literature review. PMID- 2210113 TI - CHA AIDS video now complete. PMID- 2210114 TI - Productivity indicators for long-term care. PMID- 2210115 TI - Diabetologia--25 years. PMID- 2210116 TI - Use of a new gas chromatograph isotope ratio mass spectrometer to trace exogenous 13C labelled glucose at a very low level of enrichment in man. AB - The use of 13C labelled glucose in human metabolic studies has been limited by the high cost of the tracer and the problems of measuring low 13C isotopic abundance in plasma glucose. In the present work we describe a new gas chromatograph-isotope ratio mass spectrometer allowing the measurement of a 0.001 atom % increase in 13C abundance over baseline, on a nanomole glucose sample. Studies were performed in rats and in human subjects. The rate of glucose appearance in 24 h fasted rats using D-[1-13C] glucose as tracer and analysed by this new method was found to be 10.4 +/- 0.7 mg.kg-1.min-1, a value 21% lower than that found using D-[6,6-2H2] glucose as tracer (13.1 +/- 1.1 mg.kg-1.min-1) analysed by classic gas chromatography-mass spectrometry. The new method was also used to trace, in combination with D-[6,6 2H2] glucose, the metabolic fate in human subjects of two oral glucose loads (0.5 g.kg.-1,1 g.kg.-1) labelled with 0.1% D-[U-13C] glucose. During the six hours following the glucose load, it was found that total glucose appearance was 0.97 +/- 0.04 g.kg.-1 and 1.2 +/- 0.04 g.kg.-1, exogenous glucose appearance was 0.51 +/- 0.02 g.kg.-1 and 0.84 +/- 0.04 g.kg.-1, endogenous glucose production was 0.44 +/- 0.04 g.kg.-1 and 0.35 +/- 0.06 g.kg.-1 after the 0.5 and 1 g.kg.-1 load respectively. These values are similar to those reported using glucose labelled with radioactive isotopes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210117 TI - High-performance liquid chromatography analysis of circulating insulins distinguishes between endogenous insulin production (a potential pitfall with streptozotocin diabetic rats) and islet xenograft function. AB - Porcine islets of Langerhans were microencapsulated according to the alginate polylysine procedure, and implanted into the peritoneal cavity of 15 streptozotocin-induced (70 mg/kg) diabetic rats (6000 microencapsulated islets per rat). In four animals, a sustained decrease in plasma glucose level below 8.3 mmol/l was observed for up to nine months. However, it was possible to recover microcapsules from the peritoneal cavity of only one rat, and they were found to be damaged and containing no detectable tissue. When insulin in the plasma of three of these animals was analysed by reversed phase high-performance liquid chromatography, only rat insulins I and II, but not porcine insulin was detectable, indicating unambiguously that at the time of analysis, the correction of diabetes in these animals was due to the function of the recipient's own pancreas rather than the continued, long-term, function of the implanted porcine islets. These data confirm that in this model of diabetes, function of the host pancreas can resume following islet transplantation, leading in turn to the potential for a major bias in the interpretation of the data. In the case of an islet xenograft, when the donor's and recipient's insulins can be separated by high-performance liquid chromatography, this non-invasive analytical method should prove useful for identifying the source of insulin in the circulation, and thus the relative functional status of the endogenous and transplanted islets. PMID- 2210118 TI - Traditional plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice. AB - The effects on glucose homeostasis of eleven plants used as traditional treatments for diabetes mellitus were evaluated in normal and streptozotocin diabetic mice. Dried leaves of agrimony (Agrimonia eupatoria), alfalfa (Medicago sativa), blackberry (Rubus fructicosus), celandine (Chelidonium majus), eucalyptus (Eucalyptus globulus), lady's mantle (Alchemilla vulgaris), and lily of the valley (Convallaria majalis); seeds of coriander (Coriandrum sativum); dried berries of juniper (Juniperus communis); bulbs of garlic (Allium sativum) and roots of liquorice (Glycyrhizza glabra) were studied. Each plant material was supplied in the diet (6.25% by weight) and some plants were additionally supplied as decoctions or infusions (1 g/400 ml) in place of drinking water to coincide with the traditional method of preparation. Food and fluid intake, body weight gain, plasma glucose and insulin concentrations in normal mice were not altered by 12 days of treatment with any of the plants. After administration of streptozotocin (200 mg/kg i.p.) on day 12 the development of hyperphagia, polydipsia, body weight loss, hyperglycaemia and hypoinsulinaemia were not affected by blackberry, celandine, lady's mantle or lily of the valley. Garlic and liquorice reduced the hyperphagia and polydipsia but did not significantly alter the hyperglycaemia or hypoinsulinaemia. Treatment with agrimony, alfalfa, coriander, eucalyptus and juniper reduced the level of hyperglycaemia during the development of streptozotocin diabetes. This was associated with reduced polydipsia (except coriander) and a reduced rate of body weight loss (except agrimony). Alfalfa initially countered the hypoinsulinaemic effect of streptozotocin, but the other treatments did not affect the fall in plasma insulin. The results suggest that certain traditional plant treatments for diabetes, namely agrimony, alfalfa, coriander, eucalyptus and juniper, can retard the development of streptozotocin diabetes in mice. PMID- 2210119 TI - Incidence of juvenile type 1 (insulin-dependent) diabetes mellitus in France. AB - The incidence rate of juvenile Type 1 (insulin-dependent) diabetes in France was reported as the lowest in Europe 13 years ago, but during the recent years increasing rates have been observed in different European countries. A prospective programme has been designed to study the incidence rate of Type 1 diabetes in patients up to 20 years of age in four regions located in the north and south of France (population less than 20 years = 2.31 million inhabitants; 15% of the French population). All cases were independently identified by four specially trained research assistants through hospital admission files, paediatricians, diabetologists and general practitioners. A specific questionnaire was filled out for each newly diagnosed case. Degree of ascertainment was 96% with the data from Securite Sociale, the French National Health Insurance. In 1988, 166 cases of juvenile Type 1 diabetes were identified. The incidence rate was 7.17 cases per 10(5) children (95% confidence interval = 6.1-8.2/10(5). The values were not statistically different among the four regions. Age specific incidence rates were as follows: 0-4 years = 3.8; 5-9 years = 8.0; 10-14 years = 9.7 and 15-19 years = 7.3/10(5). Sex ratio was 1.2 (male/female). These data indicate that incidence of juvenile Type 1 diabetes in France was higher in 1988 than previously reported but remains lower than in Northern Europe. This is consistent with the concept of a north to south gradient of the disease. PMID- 2210120 TI - International variations in mortality among diabetic patients: the WHO Multinational Study of Vascular Disease in Diabetics. AB - Mortality among 4740 diabetic men and women aged 35-55 years participating in the WHO Multinational Study of Vascular Disease in Diabetics has been studied. Ten of the original centres (Warsaw, Berlin, Havana, Arizona, Oklahoma, Hong Kong, Switzerland, London, Tokyo, Zagreb) were able to identify the life/death status of their study participants on 1 January 1983, giving an average follow-up period of six to seven years. All-cause mortality rates in males varied about threefold among the ten participating centres with the highest rates in Warsaw, Berlin and Havana and the lowest rates in Tokyo and Zagreb. All-cause mortality rates for females varied about fourfold with the highest rates in Warsaw and Oklahoma and the lowest rates in Tokyo. The proportion of deaths ascribed to circulatory disease varied among the centres ranging from 32% for males and 0% for females in Tokyo to 67% for males and 47% for females in London. There was an excess all cause mortality in males compared to females for all centres except Zagreb. This excess also applied to circulatory diseases in general, ischaemic heart disease in particular and occurred in both insulin-dependent and non-insulin-dependent diabetic patients. Death rates for insulin-dependent diabetic patients were generally higher than those for non-insulin-dependent patients. PMID- 2210121 TI - Regulation of insulin release in persistent hyperinsulinaemic hypoglycaemia of infancy studied in long-term culture of pancreatic tissue. AB - Pancreatic tissue was obtained during therapeutic subtotal pancreatectomy from five infants with persistent hyperinsulinaemic hypoglycaemia of infancy (so called nesidioblastosis). Collagenase digests of the specimens were cultured in RPMI 1640 medium on extracellular matrix-coated plates. Acute insulin secretion showed minimal sensitivity to changes in glucose concentration. Sensitivity to other nutrient secretagogues such as glyceraldehyde, leucine, alpha ketoisocaproic acid and arginine was variable, showing either diminished or absent response. On the other hand, stimulators of Beta cell cAMP and modulators of the phosphoinositide-protein kinase C pathway were effective inducers of insulin release. The response to cAMP stimulators was independent of the glucose concentration. Although insulin output was high in the absence of glucose, this was not due to passive leak of hormone, since both removal of calcium and addition of somatostatin and epinephrine inhibited the secretion. Beta cells were more sensitive to somatostatin than epinephrine; however, both agents failed to completely suppress the release even at suprapharmacological concentrations. Although it cannot be excluded that the culture conditions affected Beta cell function, the present findings may suggest that cultured Beta cells in persistent hyperinsulinaemic hypoglycaemia of infancy behave like fetal Beta cells at early developmental stages. PMID- 2210122 TI - Association of plasma triglyceride and C-peptide with coronary heart disease in Japanese-American men with a high prevalence of glucose intolerance. AB - In a community-based study of second-generation Japanese-American men known to have a high prevalence of both Type 2 (non-insulin-dependent) diabetes and impaired glucose tolerance, there was a highly significant association of coronary heart disease with glucose intolerance in a study sample of 219 men. Intra-abdominal cross sectional fat area determined by computed tomography was significantly elevated in men with coronary heart disease even after adjustment for glucose intolerance and body mass index (p = 0.026). Other differences that were significantly related to coronary heart disease after adjustment for glucose intolerance were lower high density lipoprotein cholesterol levels (p = 0.001), elevated total triglyceride and very low density lipoprotein triglyceride (p less than 0.001), and elevated fasting insulin and C-peptide levels p = 0.001. When these variables were tested in a stepwise multiple logistic regression model, significant independent associations with coronary heart disease were found only for total triglyceride and fasting C-peptide after adjustment for glucose tolerance status. Variables identified to be associated with coronary heart disease were interpreted as representing or manifesting an insulin resistant state. Thus, insulin resistance may be the underlying risk factor aetiologically linking glucose intolerance with coronary heart disease. PMID- 2210123 TI - Impaired glucose tolerance precedes but does not predict insulin-dependent diabetes mellitus: a study of identical twins. AB - Non-diabetic identical twins of insulin-dependent diabetic patients were studied within five years of the diagnosis of their index twin in order to determine whether changes in intermediary metabolism precede the onset of insulin-dependent diabetes mellitus. Two studies were performed: a cross-sectional study of 12 non diabetic twins and a prospective study of a separate group of 41 non-diabetic twins. Of the 12 twins tested in the cross-sectional study six developed insulin dependent diabetes and six did not; the six who developed diabetes were given an oral glucose load a mean of 10 months before diagnosis; they then had normal fasting blood glucose levels but worse glucose tolerance than control subjects (120 min post-load (mean +/- SD) blood glucose 8.5 +/- 3.5 vs 4.9 +/- 0.9 mmol/l respectively, p less than 0.05). However, blood lactate, pyruvate, alanine, glycerol, 3-hydroxybutyrate and serum insulin levels were similar. In contrast, the six twins in this cross-sectional study who did not develop diabetes and are now unlikely to do so, as a group, had no significant changes compared with the control subjects though one had impaired glucose tolerance. To determine the predictive value of impaired glucose tolerance a separate group of 41 non diabetic twins was studied prospectively for 8 to 22 years having a total of 147 glucose tolerance tests in this period; in this group six developed diabetes. Eight of the 41 had impaired glucose tolerance; impaired glucose tolerance was found in four of the six who developed diabetes as compared with only four of the 35 who did not (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210125 TI - [The formation of a "cold reserve" in the palms during rising neuroemotional tension]. PMID- 2210124 TI - Theophylline protects against diabetes in BB rats and potentiates cyclosporine protection. AB - Type 1 (insulin-dependent) diabetes mellitus results from autoimmune cell mediated destruction of pancreatic islet Beta cells. Since theophylline has suppressive effects on immune responses, we sought to determine if this agent might protect against destruction of islet Beta cells in diabetes-prone BB rats. Diabetes-prone rats were divided into four groups and treated, from age 30 to 125 days, with: (a) no treatment (control), (b) theophylline 2 mg.ml-1 added to the drinking water, (c) cyclosporine 5 mg.kg-1.day-1 administered by gavage, and (d) theophylline plus cyclosporine. By age 125 days, diabetes (glucosuria and serum glucose greater than 11 mmol.l-1) had appeared in 15 of 17 (88%) of control rats, 10 of 18 (56%) on theophylline, 6 of 17 (35%) on cyclosporine, and 1 of 17 (6%) on theophylline plus cyclosporine. Protection against diabetes by theophylline and cyclosporine was associated with preservation of pancreatic Beta cell mass (insulin content). The protective effects of combination therapy with theophylline and cyclosporine were achieved at very low serum concentrations of cyclosporine. These findings suggest that theophylline may be a useful adjunct in the immunosuppressive therapy of Type 1 diabetes. PMID- 2210126 TI - [Changes in human psychosomatic status under duty-watch working conditions]. PMID- 2210127 TI - [The adaptation to extreme natural and technogenic factors in trained and untrained subjects under the influence of adaptogens]. PMID- 2210128 TI - [The coherent structures of the electrical activity of the human cerebral cortex]. PMID- 2210130 TI - [A review of the article by V. V. Gnezditskii The detection of an evoked potential to a single stimulus--a method for spatial synchronous averaging]. PMID- 2210129 TI - [The detection of an evoked potential to a single stimulus--a method for spatial synchronous averaging]. PMID- 2210132 TI - [The state of the areas around the electrodes during the long-term implantation of gold electrodes]. PMID- 2210131 TI - [The ecological and biomedical aspects of the problem of environmental pollution by nitrates and nitrites]. PMID- 2210133 TI - [Human functional states during electrosleep]. PMID- 2210134 TI - [Changes in the central and cerebral hemodynamics of 15- to 16-year-old schoolchildren working with computers]. PMID- 2210135 TI - [The effect of spontaneous respiration on the dimensions of the heart ventricles in healthy subjects (based on echocardiographic data)]. PMID- 2210136 TI - [The effect of the blood flow to the hands on their surface thermal relief during direct and indirect heating]. PMID- 2210137 TI - [A model for recognizing body functional states based on a mathematical analysis of the heart rhythm]. PMID- 2210138 TI - [A method for the complex analysis of the heart contractile rate by an analog procedure and using a computer operating in real time]. PMID- 2210139 TI - [The types of human autonomic reactions during the solving of creative imagination tasks]. PMID- 2210140 TI - [Evoked potentials during fixation of the glance and saccadic eye movements in man]. PMID- 2210141 TI - [The dynamics of the stable brain potential during the hyperbaric oxygenation of patients with disorders of the cerebral circulation of different origins]. PMID- 2210142 TI - [The neurophysiological mechanisms of the effects of normal transcranial micropolarization and during the modelling of emotional disorders]. PMID- 2210143 TI - [Electrophysiological research on the functional organization of the human brain during directed attention. II. Normal children 11 to 12 years old]. PMID- 2210144 TI - [The characteristics of the renin-angiotensin system, the central hemodynamics and the vascular reactivity in healthy subjects with a low plasma renin activity]. PMID- 2210146 TI - [Changes in the cholesterol content of the blood serum during physical work and training]. PMID- 2210145 TI - [The functional state of the right ventricular myocardium in patients with a secondary interatrial septal defect complicated by bacterial endocarditis before and after correction of the defect]. PMID- 2210147 TI - [The long-term postactivation changes in the contractile properties of human skeletal muscle]. PMID- 2210148 TI - [The effect of long-term nociceptive stimulation on human motor functions]. PMID- 2210149 TI - [The psychological characteristics of the personality of older workers]. PMID- 2210151 TI - Unesco and U.S. PMID- 2210150 TI - [Automated systems in the comprehensive assessment of human health and adaptive potentials]. PMID- 2210152 TI - Fingers-crossed celebration of gene therapy. PMID- 2210153 TI - Heart failure: mechanisms of cardiac and vascular dysfunction and the rationale for pharmacologic intervention. AB - Congestive heart failure is a complex clinical syndrome that has its basis in an abnormality of myocardial cell function resulting in impaired ventricular performance, exercise intolerance, and ventricular arrhythmias. The functional defect in myocardial performance may be related to alterations in receptor function, in regulatory proteins, or in biochemical mechanisms. Remodeling of the left ventricle has been observed to play an important role in the natural course of heart failure. The complex interplay between cellular elongation, reactive hypertrophy, and the influence of the change from ellipsoid to spheroidal shape of the left ventricle after acute myocardial infarction are just beginning to be understood. Prevention of this remodeling effect by pharmacologic intervention is being widely explored, although the mechanisms are poorly defined. Impedance to left ventricular ejection is also an important determinant of cardiac performance in heart failure. Constriction of arteriolar resistance vessels and reduction in compliance of arterial conductance vessels is a common manifestation of heart failure and may be under the influence of neural, hormonal, endothelial, and local regulatory factors. Increased tone of venous capacitance vessels contributes to a shift of blood centrally and to an increase in ventricular preload. Vasodilator drugs by relaxing the arterial, arteriolar, and venous vasculature result in a reduction in impedance and left ventricular afterload and a decrease in cardiac filling pressure and preload. Structural changes of hypertrophy and remodeling apparently contribute to the changes in resistance, compliance, and capacitance in the vasculature. Treatment of heart failure is aimed at relieving symptoms and prolonging life. Interventions to improve left ventricular function are critical to symptom relief. Vasodilators have been most effective for this purpose, and new positive inotropic drugs are being tested for efficacy. Long-term benefit may require interference with the myocardial and peripheral vascular remodeling processes that lead to progressive depression of ventricular performance. New insights into the cellular and subcellular mechanisms of this progression are critical to the development of innovative therapeutic strategies. PMID- 2210154 TI - Doxorubicin cardiotoxicity: analysis of prevailing hypotheses. AB - Anthracyclines, such as doxorubicin and daunorubicin, are highly effective anticancer agents that produce a well-described but incompletely understood cardiac toxicity. According to a popular hypothesis, anthracyclines injure the heart by generating oxygen-centered free radicals. This free radical hypothesis, however, appears to be inconsistent with many observations, such as the frequent failure of anthracyclines at cardiotoxic doses to produce evidence of increased free radical generation. Other explanations of cardiotoxicity involve platelet activating factor, prostaglandins, histamine, calcium, and C-13 hydroxy anthracycline metabolites. These C-13 hydroxy metabolites, on the basis of in vitro data, are considerably more potent than parent compounds as myocardial depressants and as inhibitors of ATPases of sarcoplasmic reticulum, mitochondria, and sarcolemma. Further studies will be required to determine whether metabolites or the other putative injurious agents discussed contribute substantially to the cardiomyopathy of anthracycline therapy. The hypotheses presented in this paper should provide a useful framework for subsequent investigations into the mechanisms of anthracycline cardiotoxicity. PMID- 2210155 TI - In vivo models of arterial thrombosis and thrombolysis. AB - This year approximately 1.5 million Americans will undergo a myocardial infarction (MI). Of those who make it to the hospital (approximately 1.2 million), only about 20% will receive thrombolytic therapy. Multiple factors contribute to this dismaying figure, but most of them are risk/benefit-related. Moreover, of those receiving lytic therapy, the coronary arteries of as many as one-third may not reopen, and of those that do undergo coronary thrombolysis, an unacceptable fraction will experience reocclusion acutely. Thus, despite significant progress, major challenges for antithrombotic and thrombolytic therapy remain. Promising results with aspirin provide some hope that the figures above can be altered favorably. Efforts are under way in industry and academia to develop drugs to accomplish one or more of the following: lower the incidence of MI, prevent the development of unstable angina or retard its progression to frank MI, increase the inclusion window for lytic therapy, raise the percentage of patients undergoing successful thrombolysis, and maintain coronary patency. During the period that thrombolytic agents have come into vogue important advances have been made in our understanding of platelet function, coagulation, and the endogenous fibrinolytic system. These have spurred the development of novel drugs, such as platelet fibrinogen receptor antagonists, plasminogen activators, and inhibitors of factor IIa (thrombin) and XIIIa. Evaluation of these agents for their antithrombotic or profibrinolytic activity requires relevant animal models of thrombosis. Despite appropriate concerns about their clinical relevance, these models bridge the wide gap between test tube assays of aggregation or coagulation and humans. PMID- 2210156 TI - The new metabolism: molecular genetics in the analysis of metabolic regulation. AB - Genetics is a powerful tool for analyzing metabolic regulation in bacteria, permitting definitive identification of key regulatory enzymes, and assignment of cause and effect relationships between molecular mechanisms that control activity of regulatory enzymes and flow of metabolites through the pathways of intermediary metabolism. In homeothermic vertebrates, however, traditional genetic analysis of metabolic regulation is difficult or impossible. Despite an enormous amount of factual information about metabolic pathways in vertebrates, our understanding of regulatory mechanisms is based largely on correlations between regulation of the activity of a purified enzyme by an effector and variations in the intracellular concentration of that effector under conditions that modulate flow of metabolites through the relevant metabolic pathway. Newly developed molecular genetic and gene transfer methods can now be used to study metabolic regulation in vertebrates. Some of these methods will be described in short reviews of the mechanisms by which diet, hormones, and tissue-type regulate transcription of the genes for L-type pyruvate kinase and phosphoenolpyruvate carboxykinase. Application of these techniques to analyses of structure/function in intact cells and animals will be illustrated with recent work on the receptor for low density lipoproteins and cyclic AMP-dependent protein kinases. PMID- 2210157 TI - Relationship of cell growth to the regulation of tissue-specific gene expression during osteoblast differentiation. AB - The relationship of cell proliferation to the temporal expression of genes characterizing a developmental sequence associated with bone cell differentiation can be examined in primary diploid cultures of fetal calvarial-derived osteoblasts by the combination of molecular, biochemical, histochemical, and ultrastructural approaches. Modifications in gene expression define a developmental sequence that has 1) three principal periods: proliferation, extracellular matrix maturation, and mineralization; and 2) two restriction points to which the cells can progress but cannot pass without further signals. The first restriction point is when proliferation is down-regulated and gene expression associated with extracellular matrix maturation is induced, and the second when mineralization occurs. Initially, actively proliferating cells, expressing cell cycle and cell growth regulated genes, produce a fibronectin/type I collagen extracellular matrix. A reciprocal and functionally coupled relationship between the decline in proliferative activity and the subsequent induction of genes associated with matrix maturation and mineralization is supported by 1) a temporal sequence of events in which an enhanced expression of alkaline phosphatase occurs immediately after the proliferative period, and later an increased expression of osteocalcin and osteopontin at the onset of mineralization; 2) increased expression of a specific subset of osteoblast phenotype markers, alkaline phosphatase and osteopontin, when proliferation is inhibited; and 3) enhanced levels of expression of the osteoblast markers when collagen deposition is promoted, suggesting that the extracellular matrix contributes to both the shutdown of proliferation and development of the osteoblast phenotype. The loss of stringent growth control in transformed osteoblasts and in osteosarcoma cells is accompanied by a deregulation of the tightly coupled relationship between proliferation and progressive expression of genes associated with bone cell differentiation. PMID- 2210158 TI - Scanning tunneling microscopic images show a laminated structure for glycogen molecules. AB - Scanning tunneling microscopy (STM) has been used to examine glycogen molecules. Individual molecules were approximately ellipsoidal with dimensions in the 20- to 60-nm range. Images of the glycogen molecular surfaces have a laminar appearance. The layered features seen on the surfaces of the molecules suggest that glycogen may grow from one edge as a laminar structure to form an ellipsoid rather than originating at a central point with radial growth of the oligosaccharide chains to form a sphere. The results of these studies indicate that STM can be used to determine details of polysaccharide structures. PMID- 2210159 TI - Investigation of scientific misconduct: virtue or hypocrisy? PMID- 2210160 TI - [A prospective study of the evolution of coronary lesions: clinico-morphologic correlations]. AB - In order to evaluate the evolution (progression and regression) of coronary atherosclerosis, 61 patients (8 with stable angina, 9 with unstable angina, 15 with a recent myocardial infarction, 29 with multivessel coronary artery disease and treated with successful one-vessel angioplasty) were enrolled in a prospective study. In the angioplasty group, only untreated vessels were considered for the analysis. All patients underwent coronary angiography before hospital discharge and after one year, in accordance with the study protocol. In 13 patients (21%) a repeat angiography was performed at 6.3 +/- 2.7 months for clinical reasons (myocardial infarction, changing pattern angina, angina recurrence). All patients were asymptomatic or mildly symptomatic on medical therapy between the angiographic studies. Progression (decrease in internal luminal diameter at the site of stenosis greater than or equal to 20%; new onset of lesions, new episodes of total occlusions) was found in 16 out of 216 stenoses (7%) and in 14 out of 61 patients (23%). Regression (increase greater than or equal to 20% in internal luminal diameter; reopening of a previously occluded vessel) was found in 11 out of 227 lesions (5%) and in 7 out 61 patients (11%). At repeat angiography, the increase in severity was found more frequently in stenoses greater than 5 mm in length and with a reduction of greater than or equal to 75% in luminal diameter. Regression was more frequent in the occluded vessel supplying a recently infarcted area. No significant relationship was observed between lesion morphology (concentric, eccentric, with plaque ulceration, thrombi, border irregularities) and progression or regression. Lesions with plaque ulceration (with or without superimposed thrombi) were found only in patients submitted to coronary angiography close to an acute ischemic attack. Morphologic regression (disappearance of ulceration, border irregularities, thrombi) was also observed, without any significant changes occurring in the severity of the underlying stenosis. Progression may occur independently of worsening in the clinical status; on the contrary, regression was only found in patients without new cardiac events. Nevertheless, clinical status does not seem to be closely correlated to progression, regression, or changes in plaque morphology. PMID- 2210162 TI - [Life threatening hyperkinetic ventricular arrhythmias in late-phase myocardial infarction: what line of action should be taken?]. PMID- 2210161 TI - [Malignant ventricular arrhythmias in the subacute and late phases of myocardial infarction. Clinical arrhythmological characteristics and prognostic value]. AB - The purposes of this study are as follows: 1) to describe the clinical and arrhythmological characteristics of 30 patients (23 male, 7 female, mean age: 61 years) who suffered from episodes of ventricular tachycardia and/or ventricular fibrillation between the 7th and the 90th day following acute myocardial infarction; 2) to evaluate the effectiveness of treatment with amiodarone also taking into account the results of electrophysiologic study; 3) to correlate our results with data from previous studies. The site of the acute myocardial infarction was anterior in 16 patients, inferior in 12, and anterior and inferior in 2. Twenty patients had early post-acute myocardial infarction complications (67%) such as cardiac failure (16), bundle branch blocks (9) and ventricular fibrillation in the first 48 hours (6). The mean ejection fraction was 33 +/- 8% and a left ventricular aneurysmatic evolution was observed in 13 patients (43%). The first episodes of spontaneous ventricular arrhythmias occurred after a mean interval of 32 +/- 24 days following acute myocardial infarction. These occurred in the form of ventricular fibrillation in 19 patients (63%) and of ventricular tachycardia in the other 11 (37%). The patients experienced 5.6 +/- 5 episodes of ventricular fibrillation or ventricular tachycardia. Of the 30 patients, 28 received amiodarone, 1 procainamide and 1 propafenone. Five of the 28 patients treated with amiodarone were also given either procainamide or propafenone due to the early recurrence of ventricular tachycardia or fibrillation. One patient underwent early left ventricular aneurysmatic resection due to refractory ventricular fibrillation. Two groups of patients were distinguished on the basis of the electrophysiologic study results obtained during anti-arrhythmic treatment: group A consisted of 17 cases in which a sustained ventricular tachycardia was inducible (57%), group B consisted of 13 cases in which a sustained ventricular tachycardia was not inducible (43%). During a mean follow up period of 31.6 +/- 26 months the total mortality rate was 23% in group A and 46% in group B (p = ns), the incidence of sudden death was 17% in group A and 23% in group B (p = ns), the incidence of non fatal ventricular tachycardia or ventricular fibrillation recurrences was 24% in group A and 0% in group B (0.05 less than p less than 0.1). One group A patient successfully underwent a heart transplant. The negative predictive value of ventricular stimulation in relation to sudden death and to non-fatal arrhythmic recurrences was 77% and 100%; the positive predictive value was 17 and 28%.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2210164 TI - [Total anomalous pulmonary venous drainage: is a surgical correction possible on the sole basis of echocardiography?]. AB - Between April '83 and August '89, 33 patients with total anomalous pulmonary venous drainage were studied at the department of Cardiology in Bergamo. There were 18 males and 15 females, aged between three days and 8 months (average: two months). In this study only cases of isolated total anomalous pulmonary venous drainage were taken into consideration. The patients underwent echocardiographic examination with ATL MK 600, Vingmed 700, ATL Ultramark 9 with 3.5; 5; 7.5; MHz transducers; in the last three years the echocardiographic examination was integrated by continuous and pulsed wave Doppler and, in the last year, by color Doppler. The morphologic diagnosis was routinely established by means of the sequential approach method. A common feature in all types of total anomalous pulmonary venous drainage was the impossibility of defining the connections of the pulmonary veins with the left atrium. Furthermore, patients had a volume overload of the right heart, and atrial septal defects of various sizes. The site of anomalous drainage of the pulmonary veins was assessed by means of multiple cuts from subcostal, precordial and suprasternal windows. The echocardiographic diagnosis was exact and complete in 29 cases (87.9%), and in four cases it was incomplete but basically correct (12.1%). The anatomical findings were confirmed during cardiac surgery in 32 cases and by autopsy in one case of supracardiac total anomalous pulmonary venous drainage in a critically ill patient, who died before surgery. Of the 32 patients who underwent surgical correction, 20 (62.5%) had only an echocardiographic diagnosis, which resulted correct in all cases. The majority of patients with isolated TAPVD can be confidently diagnosed by means of echocardiography, thus, avoiding preoperative catheterization. PMID- 2210163 TI - [Hypothermia treatment of junctional ectopic tachycardia after surgical repair of congenital heart defects]. AB - Junctional ectopic tachycardia after surgical repair of congenital heart defects is associated with high mortality. Usually, it is transitory and resolves spontaneously, but a long period with very fast heart rate and without atrio ventricular synchrony contraction may cause low cardiac output. Treatment with common anti-arrhythmic drugs is often uneffective both in restoring sinus rhythm and in reducing heart rate. Since hypothermia is known to decrease cardiac automaticity, two infants, aged 4 and 10 months, with junctional ectopic tachycardia and low cardiac output after surgical repair of the atrio-ventricular septal defect were treated with hypothermia after unsuccessful pharmacological attempts to control the arrhythmia. Generalized hypothermia was induced with cooling-blankets and ice packs. Rectal temperature initially dropped to 30 degrees and was subsequently maintained at between 33.8 and 34.2 degrees with the heart rate between 130 and 140 m beats per minute. Trans-oesophageal atrial pacing at a higher rate allowed for sequential atrio-ventricular contraction. Signs of low cardiac output were quickly resolved. One patient was warmed-up after 12 hours of hypothermia and remained in sinus rhythm. In the other patient, the arrhythmia recurred after rewarming and a further 30-hour period of hypothermia was required. Sinus rhythm was maintained thereafter. Both patients are in stable sinus rhythm 20 and 22 months after surgery. Our experience supports the use of hypothermia as a means to control post-operative junctional ectopic tachycardia resistant conventional anti-arrhythmic drugs. PMID- 2210165 TI - [The range and prospectives of intravascular echocardiography]. PMID- 2210166 TI - [Torsade de pointes induced by quinidine: a case treated successfully with verapamil]. AB - The Authors report a case of incessant torsade de pointes, associated with QT prolongation, due to the proarrhythmic effect of quinidine, which was successfully treated with i.v. verapamil. The arrhythmia occurred after oral administration of quinidine polygalacturonate (550 mg + 275 mg + 275 mg over a 4 hour period) for the conversion of atrial fibrillation in a 41-year-old woman with mild mitral stenosis and regurgitation. Verapamil was administered as an i.v. bolus (5 mg at a rate of 1 mg/min) and with in four minutes the arrhythmia disappeared. The electrophysiological mechanisms of torsade de pointes and the potential role of Ca+(+)-channel-blocking agents in its treatment are briefly discussed. PMID- 2210167 TI - [Supraventricular aortic stenosis. A different surgical approach]. AB - A 15-year old female with William's syndrome became symptomatic for congenital supravalvular aortic stenosis. Surgery was carried out using an unpublished technique which consisted in a symmetrical enlargement of the aortic root by inserting three triangular patches of autologous pericardium. This method has the advantage of restoring normal valvular competence while respecting coronary orifices . PMID- 2210168 TI - [The circulatory system and hydrosodium volumes in chronic uremia]. PMID- 2210169 TI - [Sodium, potassium, calcium in chronic renal insufficiency]. PMID- 2210170 TI - [The influence of hemodialysis treatment on cardiocirculatory function. Causes of hypotensive crisis]. PMID- 2210171 TI - [Arterial hypertension in dialysis]. PMID- 2210172 TI - [Cardiomyopathy in uremic patients]. PMID- 2210173 TI - [Autonomic disorders in uremia]. PMID- 2210174 TI - [Arrhythmia in uremic patients in hemodialysis treatment]. PMID- 2210175 TI - [Apical hypertrophic cardiomyopathy]. PMID- 2210176 TI - [Stress, behavior and disease]. AB - For those who have attempted to attach some importance to the problem, the role played by psychological factors in disease usually is reduced to a doctrinal choice between psychoanalytic connotations and a mechanism theory based on the biology of stress. The boundaries of this choice have enormously evolved during these last years and the results of the psychobiologic approach allow us to leave this bipolar quarrel aside. The notion of stress invariably suggests the idea of a common final pathway through which environmental aggression influence the psychological equilibrium and visceral function. This notion is obsolete. Our organism has specific defence mechanisms according to the nature of the aggression. Each of these systems relies on the close relationship existing between visceral reactions and behaviour. They differ, however, by their trigger mechanisms and the somatic and psychic modalities of expression. The exteroceptive defence system is the best known. It is activated by any external aggression susceptible of endangering the animal's (including man) physical or mental being. The behaviour pattern which arises from this reaction depends on the species, but varies according to the possibilities of prevision and control of the aggression. The same is true for their hormonal and autonomous components. In the interoceptive defence system, it is essentially the gastrointestinal components related to acquired gustative aversion that have been studied. Poisoning due to ingestion of spoiled food provokes an aversion to the aliment responsible, based on its organoleptic characteristics. The mechanisms that differ according to whether the aliment can be expelled by vomiting or by acceleration of intestinal transit.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210177 TI - [Colonic motility in the irritable bowel syndrome]. AB - The importance of colonic motor disorders during the irritable bowel syndrome is recognized, but, paradoxically, their description has yet to be perfected. Among the fundamental questions that remain unanswered, three are of prime importance: a) are there one or more specific disturbances in basal colonic motility? b) can specific motor disorders be induced by certain situations, for instance, during stress? c) is there any real relationship between clinical symptoms and coexisting motor disorders? The answers to these questions are full of ambiguities; this may be explained by the difficulty with which methods of investigation are performed as well as the heterogeneous character of the disorders. Presently, recording colonic myoelectric activity over a 24 hour period or more might prove to be useful in increasing our knowledge on motor disorders. It is not at all certain that a specific basal abnormality exists and the results of the effects of stress vary according to the methods used. Segmental hyperactivity in painful constipation, abnormal colonic response to alimentation in the case of painful bloating, and propulsive hyperactivity with absence or decrease in the "sigmoid brake" during painless diarrhea have been noted on basal motor activity recordings during sleep and after meals. Myoelectric disorders, however, are seen in only two-thirds of patients with intestinal functional disorders. "Sensitivity", personality, or other disorders, and particularly, intestinal disorders, can contribute to explain the pathophysiology of "irritable bowels" in which the role of colonic disorders has yet to be shown. PMID- 2210178 TI - [Small bowel motility in the irritable bowel syndrome]. AB - The presently available methods of study of small bowel motility in humans include manometry (or electromyography) which records the temporospatial organization of bowel contractions and determination of intestinal transit time. Investigation of subjects with the irritable bowel syndrome has shown that the small intestine has its part in the motor disturbances. The characteristics of normal motility of the small intestine are well known: the migrating motor complex (MMC) develops during the interdigestive period, typical contractions are seen during phases 2 and 3 of the MMC, the nature and the duration of the motor response to alimentation have been described. In patients with IBS, the production of the MMC is irregular during the day hours; this is most likely due to environmental solicitations and it is recognized that intensive aliess can cause transient interruption of the development of cycles. On the other hand, the MMC develops normally during sleeping hours. Contraction derangements such as non propulsed repeated contractions in the proximal intestine and contractions propulsed too frequently in the small intestine may be found during phase 2. Some of the abnormal contractions coincide with abdominal pain. After meals, the duration of interruption of the MMC is shorter than in the normal subject. Transit time is shortened in patients with diarrhea, lengthened in patients with constipation. Patients with IBS respond excessively to certain stimuli: for instance, the motor response to cholecystokinin is increased compared to the normal subject. Intake of fatty ingesta is followed by the same type of reaction: pain is often associated with abnormal contractions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210179 TI - [Intestinal sensitivity disorders and irritable bowel syndrome]. AB - Long neglected in the past, the study of visceral sensitivity (interoception) has progressed in recent years because of advances in neurobiological techniques. Dealing with the structure or the function of single neurons, these techniques have profoundly increased our knowledge about the sensitive mechanisms in the digestive tract. According to recent data, the visceral sensitivity organs are richer and more complex than imagined previously. Microphysiological techniques have shown that intestinal sensitive terminations are capable of transmitting information concerning visceral activity and physicochemical modifications of intestinal contents directly to the central nervous system. This means that visceral sensitivity intervenes under physiological as well as pathological conditions. This notion is new and of great interest. As progress was being made concerning the morphologic and electrophysiologic aspects and contemporaneous studies were establishing the richness of visceral, and particularly, intestinal, sensitive receptors, basic science research in humans and animals have emphasized the diversity of the implication of the extrinsic nervous system in pain, regulation of digestive motility, homeostasis and alimentary behaviour. Our present knowledge on the nervous and neurohumoral mechanisms has shed new light on the determinisms in digestive tract pathology. This is especially true in the irritable bowel syndrome which can be considered as an extrinsic nervous system derangement. Due to abnormal sensitivity by modification of the threshold values of sensitivity to distension, and/or to stimulation by substances such as cholecystokinin, for example, motor disorders occur. Other factors, such as stress, can be responsible for revelation or exacerbation of neurohumoral disorders. PMID- 2210180 TI - [Irritable bowel syndrome: intestinal disease or personality disturbance?]. PMID- 2210181 TI - [The hypersensitive bowel]. AB - The irritable bowel syndrome is above all a syndrome of intestinal pain. Although the intestinal disorders described in this syndrome have prompted several studies focused on intestinal motility, little has been learned from these studies increasing our knowledge on the pathophysiology of this syndrome. The demonstration of colonic hypermotility or various and slightly significant modification in small intestinal motility do not add much to our knowledge. For one, why are clinical signs such as abdominal pain, bowel movement disorders, and abdominal distension, and most likely other motor disorders, found in numerous normal subjects (14 to 30 percent of the normal population) who do not seed medical advice for intestinal signs which are, one must admit, not very alarming? Are patients who complain of functional digestive tract disorders, constantly seeking medical advice and heavy medication consumers, mentally ill (emotional patients, hypochondriacs, depressive, hysterics), are they just under great stress, or do they indeed have chronic pain pathology? A number of studies show clearly that the last hypothesis is most likely true: patients with the irritable bowel syndrome (i.e. hypersensitive bowel) have a chronic pain pathology because their threshold perception of pain is lower than in the normal population. The threshold tolerance to distension of the pelvic colon is lower in these patients than in asymptomatic patients. The gastric transmural potential is lower in patients complaining of functional intestinal disorders, and it is known that a fragile mucosa is highly sensitive to normally innocuous stimuli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210182 TI - [Characterization of intestinal function and diagnosis of irritable bowel syndrome by surveys and questionnaires]. AB - In order to obtain criteria characteristic of the irritable bowel syndrome (IBS), the authors sent out questionnaires to evaluate the bowel habits and intestinal disorders in patients with IBS and to identify and compare clinical findings with patients who had other gastroenterology pathology. In this article, we discuss the results of this survey conducted in the United States, its clinical consequences and its value in identifying characteristics of patients with the IBS. In 94.2 percent of the population studied (students and employees at the North Carolina University Hospital), stool frequency ranged from 3 per week to 3 per day. Variations were dependent on the race and sex of patients: men had more frequent bowel movements than women (9.2 vs 6.7 per week; p less than 0.0001), and Caucasians had more frequent bowel movements than Blacks (7.8 vs 6.0 per week; p less than 0.0001). Definitions of constipation and diarrhea vary, which shows that the manner in which questions are asked is very important in surveys on intestinal disorders. Symptoms suggesting IBS were found in 15 to 17 percent of cases. The group of subjects with IBS: a) were mostly women (72.6 vs 54.4 percent), b) considered that psychologic stress was a cause of intestinal disorders (84.4 vs 67.6 percent) and intestinal incomfort (68.9 vs 48.0 percent), and c) used laxatives more than once a month (12.6 vs 1.5 percent). The majority of patients (62 to 77 percent) without symptoms of IBS had never sought medical advice before for their symptoms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210183 TI - [Irritable bowel syndrome: questionnaires and scores]. AB - The goals of questionnaires and scores differ. This article emphasizes their value in the diagnosis of the irritable bowel syndrome. In 1978, Manning et al. studied patients with the irritable bowel syndrome or organic disease with a questionnaire of 15 questions. Retrospective analysis of results showed that the presence of one or several characteristic symptoms can lead to the diagnosis of the irritable bowel syndrome. We evaluated a score system based on a 5 question questionnaire and a list of 8 investigations performed to eliminate organic disease. We were able to show that this score allowed to make the diagnosis of irritable bowel syndrome with accuracy because the specificity was 97 percent and the sensitivity was 83 percent. Similar results have been obtained in other studies. Moreover, a group from India has developed a system based on 19 questions which has also proved to be very accurate in the diagnosis of the irritable bowel syndrome. PMID- 2210184 TI - [What to expect from expert systems for the diagnosis of functional bowel disorders]. AB - The goal of this study was to evaluate the computer-aided diagnosis systems used for functional intestinal disorders published between 1970 and 1989. The methodology of all prospective studies published was evaluated using a score system of 12 items, filled in by two independent observers. A total of 10 studies were identified. None of the systems studied could truly be considered as an expert system. Most systems were not methodologically sound and the median score was 11 of a possible total of 24. The two principal characteristics of functional intestinal disorders are their high prevalence and the absence of objective diagnostic criteria. Taking these two facts into consideration when elaborating a diagnostic method, expert systems should be useful for teaching purposes and for conducting prospective epidemiologic or therapeutic studies. It seems too early, however, to consider the use of veritable expert systems as an aid to the practitioner in daily practice. PMID- 2210185 TI - [Personality and psychological factors in the irritable bowel syndrome]. AB - The study of the psychologic profile of patients with the irritable bowel syndrome (IBS) has shown that psychologic aggression, personality abnormalities, psychiatric diagnostics and pathologic behaviour patterns are more frequently encountered than in normal subjects or those with other disease. Moreover, patients with IBS often relate psychological events experienced in infancy such as a lost child, divorce of parents, or sexual abuse which can affect their future and particularly their manner of seeking medical advice. As it is known that only between 23 and 38 per cent of patients with IBS seek medical advice, it is also important to know whether these psychologic characteristics are true for all subjects with these symptoms or if they are found in a particular subgroup of patients who seek medical advice because, in fact, they are really ill. Multivariate analysis was used to evaluate the medical and psychologic status of 72 patients with IBS, 82 patients with symptoms suggestive of IBS but who did not seek medical advice, and 84 normal subjects. With regard to semeiologic differences according to whether patients sought medical advice or not, there were more subjects in the first group who complained of diarrhea and pain. Moreover, there were more patients with personality abnormalities, pathologic behaviour patterns, and a lower sensitivity to stress in subjects with IBS seeking medical advice than in those with symptoms who did not seek advice (p less than 0.001) or normal subjects (p less than 0.001). There were no significant differences between the subjects with symptoms but who do not seek medical advice and the normal subjects (p = 0.21).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210186 TI - [Historical viewpoint on the irritable bowel syndrome]. AB - Contrary to common thought, the conception of the irritable bowel syndrome (IBS) is relatively old, even if the current term dates from as recently as 1944. Long ago, several ancient, and disparate terms, some of them corresponding to currently exceptional clinical pictures, were used. Does that mean that these banal complaints, currently of prime importance among the clinical signs in gastroenterology, were left aside in favor of more severe disease? Surely this is not the case because functional pain has always existed, the only problem is to know whether it was or could be recognized. It was Amboise Pare who first mentioned an ancestor to the IBS when he spoke of "windy colic" (Le Miroir de Beaute et de Sante Corporelle). The glorious kingdom of nervous, chemical, motor, buccal, and intestinal disorders predominated in Gastroenterology at the end of the nineteenth century and the two diseases suggesting functional intestinal problems, i.e. enteroptosis and chronic intestinal stasis, were relegated to second place. Mucomembraneous entercolitis represents one of the most illustrated and widely described offsprings. At the beginning of the twentieth century, progress in roentgenology has allowed to dismember the category of colitis and distinguish between functional and organic diseases. Of the many terms used, "nervous colic" and "irritable intestine" are two which suggest the pathophysiological duality of the disease. Further development of studies on colonic and intestinal motility should allow to identify the authentic motor disorders, even though some etiologies may still go recognized... PMID- 2210187 TI - [Irritable bowel syndrome in children]. AB - In the adult, the irritable bowel syndrome is characterized by intestinal transit disorders associated or not with chronic abdominal pain. Two different forms can be seen: in one, pain and constipation are predominant, while in the other, pain and diarrhea alternate. The second form is encountered with predilection in the child. Various terms can be used to name the syndrome including colitis, non specific or benign colitis, irritable bowel syndrome in the child, infantile diarrhea, and others, all of which attests to our ignorance of the pathophysiology of this disorder. This syndrome is by far the most frequent cause of chronic or recurrent diarrhea in the child. Before the age of 3 or 4 years, the principal syndrome is diarrhea, which usually appears before the age of 6 months. Onset is generally brutal, as in acute enteritis or an extradigestive infection (ENT...) but persists, or else, more often, the syndrome appears insidiously over several days. The child has soft or liquid stools of fetid odor in most cases, very rarely sourish, inhomogeneous and in which intact aliments can be found. Stools are often associated with mucous discharge, rarely with blood, and do not contain any pus. Stools are not fatty but occasionally they are sticky and adhere to the pot. During the day, stools change from well formed in the morning to soft in the evening. Their frequency varies from one day to another as well as during a given 24 hour period, ranging from one or two to 10 per day.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210188 TI - [Epidemiology and methodology of randomized therapeutic trials in patients with intestinal functional disorders]. PMID- 2210190 TI - [Therapeutic strategy in the irritable bowel syndrome]. AB - The irritable intestine is one of the most frequently encountered complaints in medical practice. Although treatment is generally difficult, a therapeutic strategy which can be used in most cases is proposed. Most patients with these symptoms do not seek medical attention. The motivation for medical consultation can however be of prime importance for adequate treatment. The attending physician must first establish the reality of disease by detailed history-taking, physical examination and sigmoidoscopy. Promoting factors such as dysentery, medications, alimentation, emotions or any other major event in the patient's life must be identified. The physician must reassure and console the patient accordingly. Bran-containing diets are reliable adjuvants for most patients. Follow-up is important to guarantee patient compliance and understanding. The essential risk in the irritable bowel syndrome is the doubtfulness which hovers over the disease entity and can be responsible for patient anxiety, or prompt expensive investigations, undesirable effects of medication or even unnecessary surgery. If the patient's complaints remain unchanged at the second medical visit, other diagnostics should be considered, thus avoiding unjustified investigations. Continued empathy with the patient is important. Medication, either for their placebo or specific symptomatic action (e. g. antidiarrheics) should be considered as well. The physician has to reassure and console the patient who does not improve. The patient can then be directed to a specialized unit, but only on the physician's specific orders. PMID- 2210189 TI - [Randomized therapeutic trials in intestinal functional disorders]. PMID- 2210191 TI - [Therapeutic perspectives in the irritable bowel syndrome]. AB - Future treatments of functional intestinal disorders (FID) are essentially dependent on the possible pathophysiologic hypotheses. Schematically, symptoms experienced by patients with FID can be attributed to intestinal (small or large intestine) motor disturbances or to visceral sensitivity derangement, which, in turn, may be primary or secondary to an anomalous response to alimentation, liberation of hormones or neuromediators, or to a "stress" situation. New therapeutic agents can be directed against the symptoms experienced by patients (? action on pain or intestinal transit disorders) or against the initial pathophysiologic mechanisms. In the treatment of functional diarrhea, several substances have been proposed recently. Encephalines are peptides with extremely short duration of action which are degraded by two membranous enzymes, encephalinase and carboxypeptidase. Recently, it has been shown that acetorphan, an inhibitor of encephalinase, is efficacious in acute diarrhea. Alpha-2 antagonists are substances which are capable of slowing intestinal transit time and increasing intestinal absorption. Their antidiarrheic action is moderate, and they do not act on abdominal pain. Molecules that do not traverse the neuromeningeal barrier but that act selectively on the digestive tract and are better tolerated are expected. In patients complaining of severe idiopathic constipation substances capable of stimulating colonic motility are useful: substance P or neurotensin analogues might prove interesting. Antagonists of opium receptors such as Naloxone have proved efficacious in the treatment of certain cases of chronic idiopathic intestinal pseudo-obstructions or severe constipation. The development of orally active substances or with hepatic elimination are a prerequisite. Therapy based on well characterized pathophysiologic abnormalities would be welcome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210192 TI - [Epidemiology of the irritable bowel syndrome]. AB - Based on recent epidemiologic studies of functional intestinal disorders, we have attempted to answer the following two questions: a) what is the prevalence of functional intestinal disorder in the Western world, b) are there epidemiologic variations in the different modes of symptomatic presentation of functional intestinal disorders? The overall prevalence of functional intestinal disorders in the Western world ranges between 17 and 23 percent according to the country considered, and is between 14 and 18 percent for the irritable bowel syndrome and 4 to 8 percent for painless constipation. The "irritable intestine" group is characterized by a sex ratio of close to one, a median age near 40, a strong influence of stress on symptoms, and the frequency of complaints such as nausea, vomiting, migraine, and pyrosis. The syndrome is seen in active subjects, who believe that they are "sick", and as such, seek medical advice often. Anxiety and depression are frequently encountered. Patients are often athletes, smokers, and have diarrhea. On the other hand, "painless constipation" is characterized by a high prevalence of women and age over 50. Often these subjects do not have any active professional activity. Stress-related and extradigestive symptoms are rare. They do not consider themselves "sick" and do not seek medical advice very often. Conversely, they use laxatives frequently. Individualization of epidemiologically different groups suggests that the pathophysiology may differ between the two groups and perhaps that there are specific therapeutic and diagnostic approaches accordingly. PMID- 2210193 TI - Esophageal squamous cell carcinoma: MRI evaluation of mediastinum. AB - Thirty-two patients with esophageal spinocellular (squamous cell) carcinoma were studied with superconductive magnet in order to evaluate local and extraluminal extent, as well as mediastinal lymph node spread of the disease. In the absence of adenopathy, the localized tumors were considered susceptible to surgical treatment. All patients were operated on within 21 days. The resectability criteria were correctly evaluated in 75% of cases; sensitivity and specificity were 86 and 67%, respectively. Unsatisfactory results were obtained in the evaluation of mediastinal adenopathies. We conclude that magnetic resonance imaging (MRI) is useful in the preoperative evaluation of resectability criteria in patients with esophageal squamous cell carcinoma. PMID- 2210194 TI - Imaging of congenital esophageal cysts in adults. AB - The radiologic imaging of esophageal cysts (EC) in adults is described. These rare cysts, often detected incidentally on routine chest radiographs, seldom produce symptoms, but they may cause precordial sensations, arrhythmias, and dysphagia. They may also bleed and become malignant. As surgical excision is the treatment of choice, the preoperative diagnosis must be exact. For this, magnetic resonance imaging (MRI) or endoscopic ultrasound seem to be the imaging methods of choice even if a plausible diagnosis can be advanced on computed tomography (CT). Chest x-ray or esophagus roentgenogram have little differential diagnostic value. PMID- 2210195 TI - Extreme diffuse adenomatous hyperplasia of Brunner's glands: case report. AB - A case of extreme diffuse adenomatous hyperplasia of Brunner's glands was clinically manifested by melena and anemia. Diagnosis was established by barium studies, endoscopy, ultrasonography, computerized tomography, and histology. The radiologic, clinical, pathologic, and differential diagnostic features are reviewed. PMID- 2210196 TI - Colobronchial and gastrocolic fistulas: rare complication of Crohn's disease. AB - A rare case of colobronchial and gastrocolic fistulas originating from the splenic flexure in a patient with Crohn's disease is presented. A computed tomographic (CT) examination of the chest first suggested the presence of the colobronchial fistula. PMID- 2210197 TI - CT detection of asymptomatic pancreatitis following ERCP. AB - Presence or absence of pancreatitis without symptoms attributable to pancreatitis was assessed by computed tomography (CT) in 31 patients who underwent CT following endoscopic retrograde cholangiopancreatography (ERCP) within a time interval of 0-9 days. Presence or absence of pancreatitis was proven by elevated or normal amylase, and/or surgery, and by symptoms related to pancreatitis. Twenty-five of the patients underwent ERCP without and six with sphincterotomies. Among the six patients, additional procedures included two stent placements, two balloon dilatations, and one basket retrieval. Eleven of 31 patients developed pancreatitis following ERCP. The incidence of pancreatitis was higher in the group with maneuvers (four of six patients or 66.7%) than that without maneuvers (seven of 25 or 28%). Asymptomatic pancreatitis was present in five of 31 patients or 16.1%, and three of these had CT evidence of severe pancreatitis. CT demonstration of pancreatitis following ERCP with or without maneuvers may not always indicate clinically relevant disease. PMID- 2210199 TI - Pancreaticoportal fistula: a rare complication of chronic pancreatitis. AB - We report a patient with chronic alcoholic calcifying pancreatitis in whom a pancreaticoportal fistula was demonstrated by endoscopic retrograde pancreatography. No complications could be ascribed to this fistula except for thrombosis of the portal, splenic, and superior mesenteric veins. An expectant conservative management was adopted. A short review of the six other cases reported in the literature is presented. PMID- 2210198 TI - Fatal pancreatitis secondary to iatrogenic intramural duodenal hematoma: a case report and review of the literature. AB - Intramural duodenal hematoma (IDH) is a rare finding in the adult, especially when related to iatrogenic complications of ulcer treatment. It can lead to biliary obstruction and pancreatitis, which proved fatal in our case. Contrast enhanced computed tomography (CT) is invaluable in detecting the abnormality and can definitely be diagnostic. PMID- 2210200 TI - Omental teratoma in an adult: a case report. AB - We recently experienced an omental teratoma in a 34-year-old woman. Ultrasonography (US) revealed a large mass of mixed echogenicity, occupying the entire lower abdomen. Computed tomography showed an inhomogeneous solid and cystic mass in the abdominal cavity containing fat and calcification. PMID- 2210201 TI - Abdominal tuberculosis in children: CT findings. AB - Tuberculous peritonitis is a rare manifestation of childhood tuberculosis. The computed tomographic (CT) scans of three patients with abdominal tuberculosis were reviewed to determine the range of abdominal involvement. This report describes the following CT features of abdominal tuberculosis: (1) diffuse lymphadenopathy involving mesenteric and retroperitoneal lymph nodes; (2) low density lymph nodes with multilocular appearance following intravenous contrast; (3) high-density ascites; (4) mottled low-density masses in the omentum; (5) thickening of the bowel wall adjacent to the mesentery; and (6) hepatic pseudotumors. These CT features of abdominal tuberculosis, in the appropriate clinical setting, should help optimize the correct diagnosis and management of tuberculosis in children. PMID- 2210202 TI - Primary macronodular hepatic tuberculosis: US and CT appearances. AB - Tuberculosis of the liver is uncommon except in association with miliary dissemination. Although hepatic involvement by tuberculosis tends to be diffuse, the macronodular or pseudotumor forms are rare. In addition, reports of actual imaging of tuberculous liver involvement are rare. A 5-year-old boy with a febrile illness due to macronodular hepatic tuberculosis, demonstrated by abdominal computed tomography (CT), and diagnosed by liver biopsy is presented. PMID- 2210203 TI - Sonographic and computed tomographic features of polycystic disease of the liver. AB - Three cases of polycystic disease of the liver (PCL) are reported. Sonography (US) and computed tomography (CT) are diagnostic and the characteristic features are described. PMID- 2210204 TI - Biliary cystadenoma: ultrasound, CT, and MRI. AB - Two cases of intrahepatic biliary cystadenoma, a rare tumor with malignant potential, are discussed. The sonographic, computed tomographic (CT), and magnetic resonance imaging (MRI) findings are presented together with clinical features of this entity and a brief review of the pertinent literature. PMID- 2210206 TI - The loop-torque maneuver: a method to facilitate intubation for enteroclysis. AB - The loop-torque maneuver is a simple technique used to facilitate intubation with an enteroclysis catheter. A braided stainless steel guidewire, 26 cm longer than the one provided with the commercially available set, is used. A loop is formed in its proximal end to facilitate torquing if the catheter engages the greater curvature or coils up in the fundus. The loop-torque maneuver led to successful intubation of all patients in this series and produced less discomfort than the double-back maneuver. PMID- 2210205 TI - Barium meal study for amyloidosis of the small intestine: measurements on radiograph. AB - In order to determine barium meal radiographic findings characteristic of amyloidosis, we measured the jejunal diameter, valvular width, and intervalvular distance in 25 patients with small bowel amyloidosis and in 30 control individuals, and compared the two groups with each other. As a result, jejunal diameter demonstrated no difference between amyloidosis cases and controls, while there was a significant difference in valvular width or intervalvular distance between the two groups. Our results indicate that objective estimates of the thickening of the valvulae and the shortening of the intervalvular distance by means of measurements of the given roentgenograms greatly contribute to the clinical diagnosis of this disease. PMID- 2210207 TI - Enteroscopy and enteroclysis: an improved method for combined procedure. AB - Enteroclysis is generally considered the method of choice for evaluating the small intestine radiographically. The combined procedure of enteroscopy and enteroclysis has been recently described as complimentary techniques for examining the small intestine. This report describes the use of a balloon catheter placed via the enteroscope, which simplifies intubation and further improves the quality of enteroclysis study. PMID- 2210208 TI - Ultrasonic and CT findings in penicillin-induced nonpseudomembranous colitis. AB - The findings of ultrasonography (US) and computed tomography (CT) of the abdomen in two cases of nonpseudomembranous colitis (NPMC) induced by penicillin are described. Both imaging methods revealed diffuse thickening of the colon in patients who were endoscopically diagnosed as suffering from this disease. The clinical and radiographic features of this entity are presented along with a brief review of pertinent literature. PMID- 2210209 TI - Radiographic demonstration of longitudinal ulcers in patients with ulcerative colitis. AB - During the past 10 years, 122 patients with ulcerative colitis were diagnosed by double-contrast barium enema and colonofiberscopy with endoscopic biopsy. Among them, five patients (4%) had longitudinal ulcers and eccentric deformities in the colon. Other radiologic findings included thumbprinting (two cases), sacculations (two cases), and inflammatory polyps (four cases). The possibility of the concomitance of ischemic colitis in cases of ulcerative colitis is discussed, due to their radiographic similarities. PMID- 2210211 TI - Diffuse cavernous hemangioma of the rectum: evaluation and MRI. AB - Computed tomography (CT) and magnetic resonance imaging (MRI) were used preoperatively to stage the extent of a diffuse rectal hemangioma in a 37-year old man with recurrent rectal bleeding. On T2-weighted MR scans, the lesion demonstrated a heterogenous signal intensity with large portions displaying the hyperintensity characteristic of hemangiomas of solid organs. MRI did not depict calcified phleboliths evident on CT and barium enema. PMID- 2210210 TI - Local recurrence of rectosigmoid cancer: what about the choice of MRI for diagnosis? AB - Local recurrence is a frequent event in the natural history of rectosigmoid cancer. The diagnostic possibilities, as well as the limits of computed tomography (CT) and transrectal ultrasonography (TRU), are well known in these conditions. The aim of our study was to define the possible role of magnetic resonance imaging (MRI). We considered 15 examinations carried out in 14 patients, seven of which were obtained before and after Gd-DTPA administration. MRI demonstrated a 93.3% accuracy, 100% sensitivity, and 83.3% specificity in relation to the presence of local recurrence. The presence of pelvic recurrence was suggested on the basis of morphological and signal criteria. The use of paramagnetic contrast gave additional information in four of seven patients. The use of Gd-DTPA may be most beneficial in patients suspected of recurrence, within 6 months of their last treatment, where the diagnosis is more difficult. PMID- 2210214 TI - Echogenic focus in gastric ulceration. PMID- 2210213 TI - Diaphragmatic endometriosis: CT and MR findings. AB - A case of endometrioma presenting as a diaphragmatic mass in a 36-year-old woman is described. The computed tomographic (CT) and magnetic resonance (MR) findings of the lesion at this rare site of involvement are illustrated, and the pertinent literature is briefly reviewed. PMID- 2210215 TI - Endoscopic treatment for submucosal tumors of the esophagus: studies in 25 patients. AB - Twenty-five patients with submucosal tumor of the esophagus were treated endoscopically. All patients underwent submucosography. The tumors were classified as intra-luminal or intra-mural types according to growth pattern. Twenty tumors were resected using electrocautery in single sessions. Another 5 lesions (more than 20 mm in diameter) were subjected to absolute ethanol injections in multiple sessions to necrotize the tissue, after the overlying mucosa was stripped off by electrocautery. These procedures were not accompanied with serious complications such as perforation or massive bleeding. Oozing bleeding occurred in 3 patients, which was easily stopped by topical injection of absolute ethanol with an endoscope. Esophageal stenosis did not occur. Local reccurence of a submucosal tumor was found in a patient after 14 months, and was retreated successfully. Although the wall of the esophagus is thinner than that of the stomach, endoscopic treatment for a submucosal tumor of the esophagus can be performed safely. Submucosography and endoscopic ultrasonography reveals the extent of the tumor in relation to the esophageal wall thickness. These examinations are helpful in preventing complications. Endoscopic treatment for submucosal tumors using electrocautery and topical injection of absolute ethanol were effective and safe. PMID- 2210216 TI - N-nitrosamines in the stomach with special reference to in vitro formation, and kinetics after intragastric or intravenous administration in rats. AB - To study the implications of nitrosation in the stomach, the formation of N nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) from nitrite and secondary amines was examined in vitro under conditions simulating gastric juice. Kinetics of NDMA were investigated after intragastric or intravenous administration of 0.2 mg/kg of NDMA in rats. NDMA and NDEA were measured using combined gas chromatography and thermal energy analyzer. Nitrite levels in human gastric juice were less than 10 micrograms/ml. Optimal pH for nitrosation was between 2.0 to 3.5. Nitrosamine formation reached maximum concentration at 3 to 6 hours. The maximum ratios of nitrosation were 0.15 and 0.11% in NDMA/nitrite and NDEA/nitrite, respectively. In the kinetic study, the highest blood levels of NDMA were observed at 5 min, reaching 174 +/- 40 and 374 +/- 40 ng/ml after administration into the stomach and duodenum, respectively. Then they decreased exponentially and were not detectable after 4 hours. Tissue levels of NDMA in the liver, spleen, kidney, lung and brain showed 70% of the blood levels. Urinary excretion of intravenously administered NDMA during the first 4 hours was less than 0.2%. These results supported the hypothesis that nitrosation occurred in gastric juice under optimal conditions, and indicated that nitrite levels were the limiting factor for nitrosation. Quick disappearance from the gastrointestinal tract suggested that the pathologic implication of nitrosamines formed in the stomach could be important for other organs. PMID- 2210212 TI - Perforation of the colon due to endometriosis. AB - Endometriosis is a common disease which affects the bowel in 12 to 35% of cases. Despite extensive serosal and intramural involvement, the intestinal mucosa usually remains intact and bowel perforation rarely occurs. We describe a patient with perforation of the sigmoid colon due to endometriosis. To our knowledge, this is the first such case to be reported in the radiologic literature. PMID- 2210218 TI - Comparative studies on the usefulness of phosphate versus glycerin enema in preparation for colon examinations. AB - Fifty of 100 persons who had undergone health screening received phosphate enema while the other 50 received glycerin enema prior to proctoscopy and barium enema, and their usefulness for preparation for colon examination was compared by a double-blind test. There was no significant difference in the degree of colonic cleansing achieved by proctoscopy and barium enema. In the subjects who received phosphate enema, the incidence of abdominal pain was less than that in those who received glycerin enema, while the effect of phosphate enema on defecation appeared later than that of glycerin enema, indicating prolonged stool retention in the subjects given phosphate enema. To study the safety of the two enemas, either phosphate enema, glycerin enema or physiological saline solution as a control was administered at 0.35 ml/animal in the rectum by 4-h closure of the anus in 10 male 7-week-old Wistar rats, and the rectal mucosa was observed for irritation macroscopically and histopathologically. Glycerin enema produced less irritation than phosphate enema diffusely in the entire area of the rectum, while phosphate enema produced more local irritation at the end of the rectum than glycerin enema. The differences in the extent of irritation and injury between phosphate and glycerin enemas were considered to be derived from differences in the pharmacologic actions of these drugs. If the extent of injury were included in the extent of irritation, the difference in irritation between phosphate and glycerin enemas would not be significant. As described above, no specific difference seem to exist in the usefulness of phosphate and glycerin enemas as preparation for colon examination. PMID- 2210217 TI - A pilot study on the usefulness of a new test for mass screening of colorectal cancer in Japan. AB - A new screening test (Shamsuddin and Elsayed, 1988) based on the enzymatic detection of the disaccharide beta-D-Gal(1----3)-D-GalNAc in the rectal mucus of patients with colorectal (CR) cancer and precancerous conditions such as inflammatory bowel disease (IBD) and polyp (precancerous lesions) was evaluated in 85 Japanese patients. Following a 15-minute reaction, a sensitivity of 80.0% (8/10) for CR cancer and 72.2% (8/11) for precancerous lesions was obtained. The overall specificity for combined CR cancers and precancerous lesions was 62.2% (28/45). Correlation with abnormal mucin production in the tissues of CR cancer and precancerous lesions was studied by high-iron diamine-Alcian blue and/or periodic acid-Schiff-Alcian blue (pH = 1.0). The agreement of the results with this test was 77.8% (7/9) for CR cancers and 75.0% (6/8) for precancerous conditions. Because of the simplicity of this test, low cost, stability of the sample and reagents and accuracy for CR cancer and precancerous lesions, the test may have potential use for mass screening of cancer and high risk individuals, particularly CR cancer in Japan. PMID- 2210219 TI - The enhancement of liver injury by lipopolysaccharide in an experimental drug induced allergic hepatitis model. AB - When guinea pigs sensitized with trinitrophenylated (TNPed) liver protein 1 (LP1) were intravenously injected with TNPed isolated hepatocytes, remarkable hepatic cell injury was induced 24 hours later. In this experimental model, drug-induced allergic liver injury was induced by using trinitrobenzen sulfonic acid (TNBS) as the hapten and LP1 as the carrier. When these sensitized guinea pigs were intravenously injected with 10 micrograms of lipopolysaccharide (LPS) along with TNPed isolated hepatocytes, serum AST and ALT levels were remarkably higher than those of the guinea pigs not injected with LPS. Hepatic cell necrosis was also more extensive, and some bleeding was observed. Although none of the guinea pigs died even after 24 hours, when 50 micrograms of LPS was injected, many of the guinea pigs started to die and the survival rate was 5% at 24 hours. These results suggested that LPS enhanced liver injury in this experimental drug induced allergic liver injury model. PMID- 2210220 TI - Effect of vitamin K on carbon tetrachloride-induced cellular damage in primary cultured rat hepatocytes. AB - The effect of vitamin K on carbon tetrachloride-induced cellular damage of primary cultured hepatocytes was investigated by estimating prothrombin activity as a parameter of cellular function. Prothrombin activity was evaluated in primary cultured rat hepatocytes using synthetic fluorogenic peptide substrates (Boc-Val-Pro-Arg-MCA). Prothrombin activity significantly increased with the addition of vitamin K and decreased by the addition of warfarin (P less than 0.05). Carbon tetrachloride caused a significant decrease of prothrombin activity and cytotoxicity in a dose dependent manner. Prothrombin activity increased after addition of vitamin K when cells were previously exposed to carbon tetrachloride for a short period, but there was no change in cells treated for a long period. Carbon tetrachloride caused a modest increase of malondialdehyde formation after a short period of exposure and a significant increase following a long period of exposure. These results suggest that: 1) prothrombin activity is a good parameter for protein synthesis in cultured hepatocytes, 2) carbon tetrachloride-induced cytotoxicity results from different mechanisms in the early phase and the late phase of exposure, and 3) vitamin K has the ability to protect hepatocytes against the carbon tetrachloride-induced cellular damage in the early phase. PMID- 2210221 TI - Detection of anti-pyruvate dehydrogenase complex antibody in primary biliary cirrhosis by an enzyme-linked immunosorbent assay. AB - The methods to detect antimitochondrial antibodies (AMAs), which are characteristically positive in primary biliary cirrhosis (PBC), have some problems in technical difficulty, sensitivity and specificity. Based on the finding that one of the major antigens corresponding to AMAs was the E2 component of pyruvate dehydrogenase complex (PDH), a very simple enzyme-linked immunosorbent assay (ELISA) to detect anti-PDH antibody (anti-PDH) has been developed in this study. Among 68 patients with PBC, IgG class anti-PDH and IgM class anti-PDH were detected in 64 patients (94.1%) and in 55 patients (80.8%), respectively, while only three cases (4.4%) were both negative. Mean optical densities (O.D.) of sera from patients with PBC were 0.536 +/- 0.386 (mean +/- SD) in IgG class and 0.308 +/- 0.342 in IgM class. No positive cases were detected in the following patients by this ELISA: 20 patients with acute viral hepatitis, 24 with chronic persistent hepatitis, 32 with chronic active hepatitis, 19 with liver cirrhosis, 19 with hepatocellular carcinoma, 19 with acute intrahepatic cholestasis, 10 with autoimmune hepatitis, and six with systemic lupus erythematosus. Among nine AMAs negative cases with PBC by conventional indirect immunofluorescence (IF) assay, seven cases were found to be positive by this ELISA. The inter-assay coefficient of the variation of this method ranged from 4.9% to 5.8% and the intra-assay coefficient of variation from 3.8% to 5.1%. Therefore, this ELISA is useful for diagnosis of PBC. PMID- 2210222 TI - Measurement of calcium content of gallstones by computed tomography and the relationship between gallbladder function and calcification of gallstones. AB - To evaluate the relationship between gallbladder function and calcification of gallstones, we studied gallbladder contractility by oral cholecystography, the computed tomography (CT) number of stones for 30 gallstone patients, calcium content of 13 stones operatively extirpated, and the degree of inflammatory change in 13 surgical gallbladder specimens. There was significant correlation between the calcium content and CT numbers of stones, and 1% of the calcium content of gallstone was approximately equal to 40 Hounsfield Units (HU) of the CT number. The calcium content of stones in patients with normal gallbladder contractility was extrapolated to be below 1.5%, while that with poor contractility ranged from 0% to 21%. Additionally there is a possibility that calcium content increases, related to the inflammatory change of gallbladder. Hence our results suggested that measurement of the CT number of stones is useful to evaluate the calcium content of gallstones, and that the gallbladder contractility could be one of the factors to influence calcification of stones. PMID- 2210223 TI - Medication-induced esophagitis in children. AB - Clinical and endoscopic features of two pediatric cases of esophageal ulcers caused by capsules of oxytetracycline and doxycycline are described. Several cases of medication-induced esophageal injury in children have been reported until now, all of which were in association with tablets or capsules. Antibiotics are known to be responsible for medication-induced esophagitis in adults. In this study, 4 cases were caused by emepronium bromide and 3 cases, including the present patients, by antibiotics. All cases but one complained of chest pain and/or dysphagia. Although the interval between the onset of the symptoms and the diagnosis varied among cases, the clinical courses were relatively uneventful, without any long-term sequelae. This clinical entity seems to be unfamiliar to pediatricians and is omitted from the differential diagnosis. PMID- 2210224 TI - Cavernous hemangioma of the stomach: a case report and review of the literature. AB - A cavernous hemangioma of the stomach in a 41-year-old Japanese man was reported. The patient had numerous hemorrhagic telangiectasias in the skin and was also diagnosed as having a submucosal tumor of the stomach by an incidental upper gastrointestinal X-ray study. Wedge resection of the stomach was performed. The tumor was located in the submucosal, proper muscular and subserosal layers. The resected specimen showed proliferation of vascular spaces lined with a layer of endothelial cells and filled with red blood cells together with a partially calcified thrombus. The histopathologic diagnosis was cavernous hemangioma of the stomach with calcified thrombus. The patient has been doing well for twenty years. We report the case and briefly review the literature. PMID- 2210225 TI - A case of multiple cavernous hemangioma of the small intestine and clinical review of the Japanese literature. AB - We report a case of multiple cavernous hemangioma of the small intestine which was diagnosed definitively before operation. A 33-yr-old male was found to have multiple polypoid lesions in the small intestine during examination for recurrent iron deficiency anemia. Plain X-ray film of the abdomen revealed multiple calcifications in the middle to lower region, suggestive of cavernous hemangioma, which was further confirmed by angiography and scintigraphy with Tc 99m-labeled red blood cells. Endoscopy during surgery was used to determine the extent of surgical resection. Seventy-three cases of hemangioma of the small intestine were reported in Japan between 1953 and 1988 and their clinical features were reviewed. PMID- 2210227 TI - CT and US findings of a rare case of amoebic liver abscess rupturing into the pericardial cavity. AB - A rare case of amoebic liver abscess that ruptured into the pericardial cavity is reported. This is the first case in the world in which CT scan and ultrasonography were performed in conjunction with each other in demonstrating the fistulous tract. CT scan, ultrasonographic and echocardiographic findings were described in detail. Pericardectomy with surgical drainage and supportive measures led to complete recovery after 37 days of hospitalization. PMID- 2210226 TI - Significance of anti-pre-S antibodies in patients with fulminant hepatic failure. AB - Anti-pre-S antibody was tested in 38 sera from patients with fulminant hepatitis (positive for HBsAg and/or IgM anti-HBc) using a specific solid phase enzyme linked immunosorbent assay (ELISA). Anti-pre-S activity was detected in 50 percent sera samples positive for HBsAg but negative for IgM anti-HBc. There were 12.5% sera positive for both HBsAg as well as IgM anti-HBc and 75% sera negative for HBsAg but positive for IgM anti-HBc. The prevalence of HBV-specific DNA polymerase activity was high in all the three groups whereas anti-HBs positivity was low. Anti-pre-S activity was observed both in the presence as well as in the absence of DNA-polymerase activity. High-anti-pre-S level in fulminant hepatitis B patients was assumed to be implicated in the fast clearance of HBsAg from circulation. PMID- 2210228 TI - Measurement of microvilli of microfold cells (M-cells) and absorptive cells in follicle-associated epithelium of mouse Peyer's patches. PMID- 2210229 TI - Changes of aldolase isozyme gene expression in CCl4 induced liver damage. PMID- 2210230 TI - Lysosomal fragility in parotid glands of rats with acute pancreatitis induced by a supramaximal dose of caerulein. PMID- 2210231 TI - Turnover of acinar cells in mouse pancreas--3H-thymidine autoradiographic investigation. PMID- 2210232 TI - Abstracts of selected papers presented at the 30th annual meeting of the Japanese Society of Gastroenterology. October 20-22, 1988, Kagoshima, Japan. PMID- 2210234 TI - Electrical and mechanical inhibition of the crural diaphragm during transient relaxation of the lower esophageal sphincter. AB - Electrical and mechanical correlates of crural diaphragm activity during swallow induced and transient lower esophageal sphincter relaxation were monitored in 12 healthy subjects. Simultaneous esophageal manometric, pH, and crural diaphragm electromyogram recordings were performed for 1 hour in the postprandial period. Swallow-induced lower esophageal sphincter relaxation was associated with minimal inhibition of the crural diaphragm, but transient lower esophageal sphincter relaxation was accompanied by marked inhibition of the crural diaphragm. The degree of lower esophageal sphincter relaxation appeared to correlate with the degree of crural diaphragm inhibition during transient lower esophageal sphincter relaxation. Inhibition of crural diaphragm during transient lower esophageal sphincter relaxation may play an important role in facilitating flow across the gastroesophageal junction. PMID- 2210233 TI - Analysis of 24-hour esophageal pressure and pH data in unselected patients with noncardiac chest pain. AB - Fourty-four unselected patients with noncardiac chest pain were studied using conventional manometry with additional edrophonium provocation and 24-hour ambulatory esophageal pH and pressure recording with a system developed by our group. New, fully automated techniques of statistical analysis of the complete set of esophageal pressure and pH signals were used to examine the temporal relation between pain, esophageal motility disturbances, and gastroesophageal reflux. The analysis used the 97.5th percentile of amplitude and duration of all esophageal contractions in each patient as well as a chi 2 test of the distribution of contraction types to determine whether a pain episode was related to abnormal motility or not. The edrophonium test results were positive in 2 patients. Only 25 patients (56.8%) had at least one pain episode (total, 111 episodes) during 24-hour recording. Thirty-three percent of the pain episodes were related to reflux and 23.4% to abnormal motility, and 43.2% were not related to an esophageal function disturbance. In the patient-oriented analysis in this study, it was required for a positive correlation that the symptom index (percentage of related pain episodes) was higher than 75%. It was found that the pain was related to reflux in 2 patients (4.6%), to reflux and motor abnormalities in 4 (9.2%), and to motor abnormalities in 2 patients (4.6%). In 36 patients (81.8%), no relation with an esophageal abnormality could be established, either because the patients had no pain during the 24-hour study, or because the pain seemed unrelated to reflux or abnormal motility. PMID- 2210235 TI - Biomechanics of cricopharyngeal bars. AB - Patients with a prominent cricopharyngeal bar visible on radiography are generally considered to have spasm of the cricopharyngeus, which is the major muscle component of the upper esophageal sphincter. This condition has been termed "cricopharyngeal achalasia." The aim of this study was to determine the pathogenesis of cricopharyngeal bars. Concurrent videofluoroscopic and manometric examinations of the pharynx and upper esophageal sphincter were performed in a cohort of six patients with prominent cricopharyngeal bars and in eight control volunteers. In each subject, swallows of 2-30-mL barium boluses were recorded. The patients with cricopharyngeal bars showed (a) normal peristaltic contraction in the pharynx, (b) normal axial upper esophageal sphincter pressure and relaxation, (c) normal flow rate across the upper esophageal sphincter, and (d) normal duration of upper esophageal sphincter opening for different bolus volumes. The major abnormalities in the patients with cricopharyngeal bars were (a) reduced maximal dimensions of the upper esophageal sphincter during the transsphincteric flow of barium and (b) increased intrabolus pressure upstream to the upper esophageal sphincter. Thus, the increase in intrabolus pressure preserved normal transsphincteric flow rates even though the upper esophageal sphincter did not open normally. Overall, the constellation of findings in the patients studied suggests that the underlying pathogenesis of their cricopharyngeal bar was reduced muscle compliance wherein the relaxed cricopharyngeus did not distend normally during swallowing. PMID- 2210236 TI - The influence of the interdigestive migrating myoelectric complex on the gastric emptying of liquids. AB - It is unknown how the interdigestive migrating motor complex influences the gastric emptying of liquids. Therefore, the gastric emptying rate of 50- and 200 mL volumes of phenol red solution were measured while monitoring contractile activity. Motor activity was recorded using a hydraulic manometric system and expressed as either the proximity of dosing time to time of appearance of phase III or as a motility index, defined as (contractile area)/(sampling interval time). After an initial lag period, emptying was log linear. With a 50-mL oral dose, the mean gastric emptying rate of the log-linear phase was successively faster during phase I (0.018 +/- 0.003 min-1), phase II (0.083 +/- 0.031 min-1), and late phase II/III (0.171 +/- 0.066 min-1) (P less than 0.05). Similarly, the mean lag time decreased successively with phases I, II, and late II/III (19.1 +/- 12.4, 7.6 +/- 5.6, and 3.8 +/- 2.8 minutes, respectively). At a 200-mL oral dose, there was no difference in the emptying rate between phase I and phase II (0.104 +/- 0.0014 vs. 0.110 +/- 0.041 min-1), but the emptying rate during late phase II/III was significantly greater (0.236 +/- 0.069 min-1); lag time was not dependent on phase. There was a statistical difference in the overall mean emptying rate between the 50- and 200-mL volumes. Also, during phase I, the emptying rate was faster for the 200-mL volume. This study shows a strong dependence of liquid gastric emptying rate and lag time on interdigestive antral motility, the emptying of small volumes being more dependent on motility phase than that of large volumes. Phase-related fluctuations in contractile activity can account for much of the reported variability in gastric emptying data. Furthermore, this study suggests that dose volume and interdigestive motor activity at the time of drug administration can affect absorption and onset of therapeutic response for some drugs. PMID- 2210237 TI - Phospholipids from rat, human, and canine gastric mucosa. Composition and metabolism of molecular classes of phosphatidylcholine. AB - To validate a recent proposal that a phospholipid lining with a high content of dipalmitoylphosphatidylcholine may protect gastric mucosa against luminal acid, it was decided to study composition and metabolism of phospholipids in the gastric mucosa. Phospholipids were analyzed in rat, human, and dog gastric mucosal surface tissue and in a chloroform/methanol-lavage of rat and canine stomach. Phosphatidylcholine and phosphatidylethanolamine were the main components. Saturated fatty acids were almost exclusively esterified at the sn-1 position of the glycerol moiety of phosphatidylcholine, and unsaturated fatty acids mainly at the sn-2 position. The disaturated class of phosphatidylcholine comprised 2%-6% of total phosphatidylcholine. Precursors of phosphatidylcholine, i.e., [32P]orthophosphate and [methyl-14C]choline, were preferentially incorporated into the disaturated molecular class 0.5-6 hours after IV administration. It can be speculated that disaturated phosphatidylcholine, although quantitatively a minor component, is specifically triggered in mucosal renewal processes. PMID- 2210239 TI - Evolution of fundic argyrophil cell hyperplasia in nonantral atrophic gastritis. AB - Fundic argyrophil cells were studied for a mean period of 68.7 months (range, 11 170) in 18 patients with fundic atrophic gastritis and achlorhydria. Initially, 12 patients had hyperplasia of the argyrophil cells, the severity of which was assessed using a semiquantitative classification based on the number of argyrophil clusters per square millimeter. At the end of the study, the degree of hyperplasia was unchanged in 9 patients, had decreased in 2, and had increased in 1; no significant increase in the number of argyrophil clusters, precarcinoid changes, or carcinoid tumors were observed and the high level of gastrinemia [mean, 4.8 (range, 1.9-8.1) times the upper limit for normal) did not change significantly. Of the 6 patients with no hyperplasia at the outset of the study, 4 continued without hyperplasia and 2 presented a low-grade hyperplasia at the 20th and 130th month. Gastrinemia increased significantly in the last patient and stayed normal in the other 5. This study argues in favor of the stable appearance of fundic argyrophil cells in patients with atrophic gastritis and stable gastrinemia. PMID- 2210238 TI - Multipolar electrocoagulation versus injection therapy in the treatment of bleeding peptic ulcers. A prospective, randomized trial. AB - This study prospectively compares multipolar electrocoagulation and injection therapy in high-risk patients with bleeding ulcers. Patients were considered for entry if they had a bloody nasogastric aspirate, melena, or hematochezia and unstable vital signs, transfusion of greater than or equal to 2 U of blood in 12 hours, or a decrease in hematocrit of greater than or equal to 6% in 12 hours. Sixty patients with endoscopic evidence of an ulcer with active bleeding (n = 26) or a nonbleeding visible vessel (n = 34) were randomly assigned to receive multipolar electrocoagulation or injection with absolute ethanol. Hemostasis was achieved in 14 of 14 actively bleeding patients with multipolar electrocoagulation vs. 10 of 12 (83%) treated with injection. No significant differences were observed between electrocoagulation and injection therapy in any parameter assessed during the hospitalization: incidence of further bleeding (6% vs. 10%), units of blood transfused after treatment (1.8 +/- 0.6 vs. 1.3 +/- 0.4), incidence of surgery for bleeding (6% vs. 7%), length of hospital stay in days (5.8 +/- 0.9 vs. 7.2 +/- 2.5), cost of hospitalization (+7160 +/- +1630 vs. +8520 +/- +2960), or mortality rate (3% vs. 3%). Treatment induced bleeding in nonbleeding visible vessels in 35% of subjects in each group, but this was controlled with continued treatment in all patients. One delayed perforation occurred 9 days after multipolar electrocoagulation. Multipolar electrocoagulation and injection therapy are of comparable efficacy in the treatment of patients with clinical evidence of a major upper gastrointestinal bleed and endoscopic evidence of an ulcer with active bleeding or a nonbleeding visible vessel. PMID- 2210240 TI - A small animal model of human Helicobacter pylori active chronic gastritis. AB - Isolation of a spiral-shaped bacterium closely related to Helicobacter pylori from the cat stomach made it possible to investigate new small animal models of gastric infection. Pure cultures of this bacterium, provisionally named "Helicobacter felis," were fed to germ-free mice. The organism colonized the stomach in large numbers in mucus and deep in the gastric pits and showed the same gastric trophism found with H. pylori. Significant histopathology was seen in all H. felis-infected mice. At 2 weeks postinfection, an acute inflammatory response was seen composed primarily of eosinophils and neutrophils. At 3 weeks, the polymorphonuclear response was more pronounced with large numbers of neutrophils in some areas forming small microabscesses. Lymphocytes also increased in number. By 8 weeks, several relatively large lymphoid nodules were present in the submucosa. Multiple small microabscesses were still present in the pyloric mucosa. This is the first animal model of bacterial gastritis to be described that shows progression from acute inflammation to persistent acute on chronic inflammation (active chronic) as is seen in human infection with H. pylori. PMID- 2210241 TI - A comparison in vitro of human and rabbit distal colonic muscle responses to inflammatory mediators. AB - The present study compared in vitro the motor responses of human and rabbit distal colonic longitudinal and circular muscle to acetylcholine, histamine, leukotrienes B4 and D4, and prostaglandins E2 and F2 alpha. The active and passive mechanical properties of these muscles were also evaluated. All muscle types were contracted by acetylcholine and histamine. Longitudinal muscle from both species was contracted by prostaglandin E2 and prostaglandin F2 alpha, although rabbit muscle was more sensitive. Prostaglandin E2 relaxed the majority of both human and rabbit circular muscle preparations that were studied. Prostaglandin F2 alpha first relaxed and then contracted circular muscle from both species. Leukotriene B4 had no effect on any tissue studied. Leukotriene D4 caused transient relaxations in a proportion of all muscle types, but the relaxations were not concentration-related. Contractile responses did not differ under isotonic recording conditions, but relaxations were much more clearly defined. Based on experiments using atropine, phentolamine and propranolol, and pyrilamine or tetrodotoxin, it was concluded that the responses of both human and rabbit distal colonic muscles to these inflammatory mediators have a similar pharmacological basis. All muscle types exhibited low passive tension and developed active tension in the range 0.8-1.2 Lo. These data strongly support the belief that after the onset of an induced colitis, the rabbit colon has value as a predictive model for the study of inflammatory mediator-induced colonic motility changes in humans. PMID- 2210242 TI - Prevention of necrotizing enterocolitis in the rat with prenatal cortisone. AB - Cortisone acetate is known to accelerate maturation of the immature intestine. The effect of prenatal administration of cortisone acetate on the morbidity and mortality of necrotizing enterocolitis was examined in a rat pup model. Pregnant rats were administered cortisone acetate, 20 mg/100 g of body weight, or normal saline by daily IP injection from day 18-21 of gestation. Rat pups were taken from the mothers before suckling was initiated, fed a simulated rat milk formula, and subjected to daily ischemic insults to produce an animal model of necrotizing enterocolitis. Both morbidity and the mortality rates were significantly improved with prenatal cortisone treatment. Maturation of the intestinal mucosal barrier was accelerated with the cortisone treatment as measured by decreased serum concentrations of a fed antigen, ovalbumin. Aerobic bacterial colonization of the small intestine and translocation of bacteria to the liver were decreased in the pups pretreated with steroids. These changes observed in a rat model of necrotizing enterocolitis may explain the decreased incidence of necrotizing enterocolitis in human infants born to mothers who received corticosteroids late in gestation. PMID- 2210244 TI - Anorectal function in incontinent patients with cerebrospinal disease. AB - Anorectal manometry and the electrical activity of the external anal sphincter were measured in 20 patients with well-defined, incomplete spinal lesions who were referred because of fecal incontinence and in 30 normal subjects. Six patients had a high spinal lesion, 11 had a low spinal lesion, and 3 had mixed high and low spinal lesions. Patients with high spinal lesions had normal basal pressures but abnormally low squeeze pressures and impaired rectal sensation. Unlike normal subjects, there was no relationship between the depth of sphincter relaxation and the distention volumes. The external sphincter responses to rectal distention and increases in intraabdominal pressure were enhanced, and leakage of perfusion fluid was uncommon. Patients with low spinal lesions had abnormally low basal and squeeze pressures, blunted rectal sensation, and showed impaired external anal sphincter responses to rectal distention or increases in intraabdominal pressures. Most of these patients leaked the infused fluid during these maneuvers. Sphincter function in patients with mixed lesions was more severely impaired than in patients with low and high spinal lesions. Patients with mixed lesions showed abnormally low basal and squeeze pressures, impaired rectal sensation, and no external anal sphincter responses to either rectal distention or increases in intraabdominal pressure. Leakage occurred during these maneuvers in all patients with mixed lesions. PMID- 2210243 TI - Neurofilament immunoreactivity in myenteric neurons differs from that found in the central nervous system. AB - Neurofilaments are 10-nm diameter protein fibers found within neurons and are composed predominantly of a triplet of polypeptides usually referred to as low-, medium-, and high-molecular-weight subunits. We describe the results of a study of myenteric plexus neurons using a panel of neurofilament triplet protein antibodies and indirect immunofluorescence techniques. Polyclonal antibodies to each of the three neurofilament subunits reliably stained myenteric neurons and their processes, indicating the presence of all three proteins in these cells. However, several well-characterized monoclonal antibodies to epitopes on high- and medium-molecular-weight subunits showed immunoreactivity in brain tissue but not in myenteric neurons and their processes. Some of the antibodies that do not stain recognize only phosphorylated epitopes, indicating that the level of neurofilament phosphorylation is very low in enteric neurons. Other antibodies that are not thought to be sensitive to the level of neurofilament phosphorylation show reduced or no staining of enteric neurons, suggesting the presence of immunologically distinct neurofilaments in these cells. These results suggest the presence of modified neurofilament structures in enteric neurons, possibly reflecting their unique mechanical character within the moving intestinal wall. PMID- 2210245 TI - Alpha 1-antitrypsin excretion in stool in normal subjects and in patients with gastrointestinal disorders. AB - Fecal clearance of plasma alpha 1-antitrypsin is used as a measure of protein leakage into the intestinal tract. In this study, the alpha 1-antitrypsin concentration in stool and the plasma clearance of alpha 1-antitrypsin in normal subjects and in a consecutive series of patients with chronic diarrhea, malabsorption, or unexplained hypoalbuminemia was determined. The normal subjects were studied in their usual state and also when they had diarrhea secondary to ingestion of lactulose, sorbitol, sodium sulfate, or phenolphthalein. The study first concluded that induced diarrhea can cause an increase in alpha 1 antitrypsin clearance; if this is not considered in establishing normal values, there may be an overdiagnosis of excess protein leakage in patients with diarrhea. Second, there is a highly significant statistical correlation (P less than 0.001) between alpha 1-antitrypsin clearance and serum albumin concentration. On average, the serum albumin falls below 3.0 g/dL (30 g/L) when the alpha 1-antitrypsin clearance exceeds 180 mL/day, a value that is about threefold higher than the upper limit of normal. Third, three of nine patients with microscopic/collagenous colitis had elevated clearance of alpha 1 antitrypsin; by contrast, abnormal alpha 1-antitrypsin clearance was not found in 23 patients with idiopathic secretory diarrhea. Fourth, fecal alpha 1-antitrypsin concentration is not a reliable index of abnormal alpha 1-antitrypsin clearance. PMID- 2210247 TI - Effect of weight reduction on hepatic abnormalities in overweight patients. AB - The effects of weight reduction on hepatic test results and physical findings related to the liver were retrospectively evaluated in 39 overweight patients screened to exclude other factors affecting the liver. An additional 11 overweight patients with primary liver disease were retrospectively evaluated to compare the effect of weight reduction in patients with liver disease with its effect in those without primary liver disease. This study showed that in overweight adults without primary liver disease, a weight reduction of greater than or equal to 10% corrected abnormal hepatic test results, decreased hepatosplenomegaly, and resolved some stigmata of liver disease. In similarly studied overweight patients with primary liver disease, some findings improved, but the changes did not correlate with a greater than or equal to 10% weight loss. Increased alanine aminotransferase activity was the most frequent hepatic enzyme abnormality in this population. For every 1% reduction in body weight, alanine aminotransferase activity improved by 8.1%. After other causes of liver disease are eliminated by clinical and biochemical parameters, weight reduction should be tried for overweight patients with abnormal hepatic test results in the absence of obvious primary liver disease as judged by clinical and biochemical parameters before extensive and expensive studies are undertaken. PMID- 2210248 TI - Pancreatic secretory trypsin inhibitor stimulates the growth of rat pancreatic carcinoma cells. AB - Pancreatic secretory trypsin inhibitor was examined for growth-promoting activity on five cell lines using standard cell culture techniques. One cell line, AR4-2J, derived from a rat pancreatic acinar cell carcinoma, responded with significantly increased incorporation of [3H]thymidine and colony formation. Pancreatic secretory trypsin inhibitor stimulated the incorporation of [3H]thymidine in liquid culture; the maximal increase was 61 +/- 10% above control (P less than 0.001) and was seen at a concentration of 10(-9) mol/L. Using a soft agarose clonogenic assay, pancreatic secretory trypsin inhibitor also consistently stimulated (3 assays) colony formation: the peak activity occurred at a concentration of 10(-10) mol/L which caused a 150 +/- 55% (mean +/- SE, P less than 0.05) increase above control. Aprotinin had no effect on the growth of AR4 2J cells and pancreatic secretory trypsin inhibitor did not bind to the epidermal growth factor receptor. AR4-2J cells were shown to produce pancreatic secretory trypsin inhibitor. The study raises the possibility that pancreatic secretory trypsin inhibitor provides autocrine stimulation of tumor cell growth. PMID- 2210246 TI - Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage. AB - In a double-blind randomized trial, the hemodynamic events following the administration of propranolol (n = 51) or a placebo (n = 51) were prospectively studied in cirrhotic patients with esophageal varices. The hepatic venous pressure gradient, heart rate, and variceal size were determined at the baseline and 3, 12, and 24 months after the beginning of therapy. Baseline values were similar in both groups. At 3 months, the hepatic venous pressure gradient decreased significantly in propranolol-treated patients (from 18.1 +/- 4.2 to 15.7 +/- 3.4 mm Hg; P less than 0.05) but not in patients receiving the placebo (19.6 +/- 6.8 to 17.5 +/- 5.3 mm Hg; NS). At subsequent time intervals this gradient decreased significantly from the baseline value in both groups. Heart rate decreased significantly in the propranolol-treated group at all times (P less than 0.001). Variceal hemorrhage occurred in 13 patients (11 placebo-, 2 propranolol-treated; P less than 0.01), all of whom had a hepatic venous pressure gradient greater than 12 mm Hg. In 21 patients (14 propranolol-, 7 placebo treated) the hepatic venous pressure gradient decreased to less than or equal to 12 mm Hg; none of them bled from esophageal varices, and their mortality rate also decreased. Because most of the bleeding events occurred during the first year (10 placebo-, 1 propranolol-treated; P less than 0.01), propranolol seems to have its protective effect during the period associated with the largest reduction in the hepatic venous pressure gradient. Because a reduction in the hepatic venous pressure gradient to less than 12 mm Hg protects from variceal bleeding and increases the rate of survival, this should be the aim of the pharmacological therapy of portal hypertension. PMID- 2210250 TI - Piezoelectric lithotripsy: stone disintegration and follow-up results in patients with symptomatic gallbladder stones. AB - One hundred symptomatic patients with radiolucent gallbladder stones were treated with a new piezoelectric lithotripter and oral chemolitholytic agents. Stone disintegration was achieved in 99 of these patients (99%) with a mean (+/- SD) maximum fragment size of 5.1 +/- 4.1 mm. Significant differences were found when the mean (+/- SD) fragment sizes of single stones less than or equal to 20 mm (4.2 +/- 2.5 mm) were compared with those of single stones greater than 20 mm (5.8 +/- 3.4 mm; P less than 0.05) and multiple stones (6.2 +/- 3.8 mm; P less than 0.05), respectively. None of the patients required anesthesia, analgesics, or sedatives before or during the treatment. The stone-free rates for all patients followed up for up to 4-12 months (mean +/- SD, 10.7 +/- 2.9 months) were 18% (1 month), 25% (2 months), 38% (4 months), 52% (8 months), and 67% (12 months). Partly significant differences were obtained in stone-free rates for single stones (less than or equal to 20 mm) compared with larger stones (greater than 20 mm) and multiple stones (P less than 0.05), respectively. Serious adverse reactions (i.e., cholestasis and pancreatitis) were observed in only 3 patients (3%). These conditions were induced by fragment impaction in the common bile duct. In 2 of these patients, endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy was required. It is concluded that piezoelectrically generated shock waves are suitable for the effective and safe disintegration of gallbladder stones in humans. The anesthesia-free and analgesia-free shock-wave application opens up the possibility to perform biliary lithotripsy as an outpatient procedure. The stone-free rate achieved in combination with oral bile acids is most promising for single stones (less than or equal to 20 mm). PMID- 2210249 TI - Bile acid transport by basal membrane vesicles of human term placental trophoblast. AB - The aim of this work was to investigate the first step in the vectorial translocation of bile acids from the fetus to the mother, which is the transfer across the basal (i.e., fetal-facing) plasma membrane of the trophoblast. Thus, the uptake of [14C]taurocholate by basal plasma membrane vesicles obtained from normal human term placentas was studied. Taurocholate retention into vesicles was studied using a rapid filtration technique that was modified to reduce the taurocholate binding to the filters and to the external surface of the vesicles. Using 100 mumol/L substrate, the membrane vesicles showed a temperature dependent, Na(+)-independent transport of taurocholate into an osmotically reactive intravesicular space. The initial rate of taurocholate influx in the presence of 100 mmol/L KNO3 followed saturation kinetics (apparent Km for taurocholate = 670 +/- 128 mumol/L; Vmax = 1.86 +/- 0.28 nmol/mg protein.60 s at 37 degrees C). Over the 6.9-7.9 pH range neither internal nor external pH nor inward nor outward proton gradients affected the uptake of taurocholate. When the electrical potential difference across the basal membrane was manipulated by external anion replacement (Cl-, SCN-, SO4(2-), or NO3-) or by valinomycin induced K(+)-diffusion potential (vesicle inside negative), taurocholate uptake was not significantly modified. Taurocholate uptake was cis-inhibited in the presence of 1 mmol/L glycocholate, 0.5 mmol/L 4,4'-diisothiocyanostilbene-2,2' disulfonate and 0.5 mmol/L sulfobromophthalein. However, 1 mmol/L probenecid or 0.5 mmol/L p-aminohippurate had no effect. Moreover, preloading the vesicles with 100 mmol/L HCO3- (but not with 100 mmol/L Cl- or 50 mmol/L SO4(2-) induced a significant enhancement in the initial rate of taurocholate uptake. In summary, these findings provide strong evidence for the presence of an electroneutral transport system for taurocholate in the basal plasma membrane of human chorionic trophoblast. They also suggest that this is likely to be an anion-exchange system. PMID- 2210251 TI - The effects of synthetic human secretin on calcium carbonate solubility in human bile. AB - This study sought to determine the effects of synthetic human secretin on ionized calcium and carbonate concentrations in human hepatic bile. Five patients with a nasobiliary drain in the right hepatic duct were studied. Three basal samples of bile were collected, each over a 15-minute period. Synthetic human secretin was then infused IV at 0.05 micrograms.kg-1.h-1 for 45 minutes followed by 0.5 micrograms.kg-1.h-1 for 45 minutes. Bile was sampled over 15-minute periods. To document return to baseline conditions, two further samples of bile were obtained over 15-minute periods 2 hours after the infusion was terminated. Bile acid concentration was determined by an enzymatic method; pH and PCO2 were measured with an automated analyzer. Total calcium was determined by inductively coupled plasma emission spectrometry and ionized calcium by an ion-specific electrode. Bicarbonate and carbonate concentrations were calculated using Henry's law and the Henderson-Hasselbalch equation. The fraction of bile sampled by the catheter was determined by Indocyanin Green recovery at the end of the experiment. Secretin caused an increase in bile flow and bicarbonate output. Bicarbonate concentrations increased from 26 +/- 3 mmol/L to 41 +/- 3 mmol/L (P less than 0.05), and chloride concentrations decreased. Mean bile acid concentrations declined significantly from 14.6 +/- 2 mmol/L to 4.7 +/- 1 mmol/L (P less than 0.05). Ionized calcium concentrations decreased from 0.7 +/- 0.005 mmol/L to 0.5 +/- 0.02 mmol/L (P less than 0.05) while pH increased significantly from 7.44 +/- 0.06 to 7.6 +/- 0.04 (P less than 0.05). Carbonate concentrations increased significantly from 0.15 +/- 0.02 mmol/L to 0.26 +/- 0.03 mmol/L, and the ion product for calcium carbonate increased significantly from 0.099 +/- 0.002 (mmol/L)2 to 0.135 +/- 0.015 (mmol/L)2 (P less than 0.05). Synthetic human secretin augments the ion product of calcium and carbonate in human hepatic bile, increasing the tendency for calcium carbonate precipitation. PMID- 2210252 TI - Human gallbladder mucosal function. Effect of concentration and acidification of bile on cholesterol and calcium solubility. AB - The most recognized function of the human gallbladder is to store bile. However, this organ is not a static reservoir. It actively modifies bile by two processes: concentration and acidification. This study was designed to simultaneously evaluate the relationship between these two physiological processes in the normal human gallbladder and to define their effects on biliary cholesterol and calcium solubility. Bile was sampled directly from the gallbladder of 78 morbidly obese patients undergoing elective gastric bypass procedures. All had negative results of intra-operative ultrasound examinations for sludge and gallstones, normal liver function tests, and no history of hepatobiliary disease. Bile salt concentrations, an indirect index of concentration by the gallbladder, ranged from 15.1-272.8 mmol/L. As [bile salt] increased, [Na+], [K+], free [Ca2+], [cholesterol], [phospholipid], and [total lipid] increased linearly; [Cl-1] decreased linearly. Molar percent cholesterol decreased from 17.2% in dilute bile to 10.1% in fully concentrated bile, suggesting that cholesterol was absorbed by the gallbladder. As bile was concentrated, cholesterol saturation index decreased curvilinearly from a maximum of 3.7 in dilute bile to 1.0-1.5 in concentrated bile. Concentration of gallbladder bile was accompanied by progressive acidification. Bile pH decreased linearly with increasing [bile salt]; [CO3(2-)] decreased curvilinearly. Despite increasing [Ca2+], CaCO3 saturation index decreased curvilinearly with increasing [bile salt] from a maximum of 3.62 in dilute bile to a minimum of 0.12 in concentrated and acidified bile. CaCO3 saturation index also decreased exponentially with decreasing pH. This study concludes that concentration of bile enhances cholesterol solubility while acidification enhances calcium salt solubility. By increasing the solubilities of these two species, gallbladder mucosal function may play a key role in preventing gallstone formation. PMID- 2210254 TI - In vivo assessment of shock-wave pressures. Implication for biliary lithotripsy. AB - During extracorporeal shock-wave lithotripsy, the pressure profile, which is generated by the lithotriptor, determines the risk of tissue damage. In the present study, the pressure distribution of a lithotriptor (Lithostar; Siemens A.G., Erlangen, Federal Republic of Germany) was investigated in 10 pigs, five of which had gallstones surgically implanted into the gallbladder. The in vivo values were compared with in vitro data. Measurements were carried out along the shock-wave transmission path at the focus within the gallbladder, the adjacent liver, the diaphragmatic surface of the right lung, and the shock-wave exit site from the skin. Interposition of ribs did not cause a significant decrease in focal positive pressure. However, a gallstone positioned in the focus caused a 30%-65% reduction in pressure, recorded immediately behind the stone. Pressures obtained in vivo were always 15%-25% lower than those measured in vitro. The spatial distributions of the positive pressure in vivo and in vitro were almost identical. There was a high correlation between the pressures in vitro and in vivo (r = 0.88; P less than or equal to 0.01). This justifies assessment of shock wave energies generated during biliary lithotripsy by extrapolation of in vitro data. It is concluded that it is possible to characterize different lithotriptors by in vitro pressure profile measurements. PMID- 2210253 TI - Actin and myosin isoforms in gallbladder smooth muscle following cholesterol feeding in prairie dogs. AB - Gallbladder smooth muscle contractility decreases after high-cholesterol feeding in prairie dogs. This decrease is not associated with alterations in the total amounts of the contractile proteins actin and myosin. The present study was designed to determine if cholesterol feeding results in alterations in the isoforms of actin and/or myosin heavy chain in gallbladder smooth muscle. Control prairie dogs were fed a trace-cholesterol diet and test animals were fed a high (1.2%)-cholesterol diet for 8 days. Although the proportion of beta-actin was unchanged, the proportion of alpha-actin in the gallbladder was less in the animals fed the high-cholesterol diet (32.6% +/- 1.5% in the control animals and 24.6% +/- 0.4% in the diet animals). On the other hand, the proportion of gamma actin was significantly greater in the cholesterol-fed animals. There were no significant differences in the proportions of the myosin heavy-chain isoforms between the two groups. Also, there was no change in the volume fraction of smooth muscle in the gallbladders from the two groups. Thus, cholesterol feeding induces a shift in actin isoforms at the same time that there is a decrease in contractility. Whether the altered pattern of actin isoforms is related to the functional changes remains to be determined. PMID- 2210255 TI - Endoscopic retrograde brush cytology. A new technique. AB - Endoscopic retrograde cholangiopancreatography has been shown to be a very valuable adjunct in the diagnosis of malignancy involving the biliary and/or pancreatic ductal system. However, characteristic endoscopic retrograde cholangiopancreatography radiographic findings associated with malignant strictures are frequently not specific and cytological confirmation becomes essential for the diagnosis. Unfortunately, the current overall diagnostic yield of positive cytology in such circumstances ranges from 18%-56% depending on the technique. A new brush device has been designed which is uniquely adapted to pancreaticobiliary strictures of varying anatomical configurations. This study shows results using this new cytology brush in a series of 53 patients with pancreaticobiliary malignancy. A significant improvement in the cytological yield of tumor confirmation was obtained with a diagnostic sensitivity of 70% and specificity of 100% using the new brush technique. PMID- 2210256 TI - Bile duct emptying in response to fat: a validation study. AB - Fatty meal sonography has been suggested to assess patients with biliary pain after cholecystectomy, but the effects of gallbladder removal on biliary dynamics has not been studied prospectively. Before elective cholecystectomy, 25 patients had their common hepatic ducts' diameter measured by ultrasonography before and after a fat stimulus. In 23, tests were repeated 1 month, 1 year, and 5 years after surgery. In preoperative studies, 5 patients showed dilatation after fat and 2 of these had stones in the common bile duct. However, another 4 patients with stones or sludge in the duct did not show dilatation, so that the response to fat was a poor indicator of patients requiring common bile duct exploration. No patient had major symptoms after surgery. At 1 month and 12 months, the response to fat was variable with more than half of those tested showing no decrease in duct size. A more consistent pattern emerged at 5 years, when 14 of 18 patients tested showed a decrease in common hepatic duct after fat; 3 were unchanged and 1 increased by 1 mm. The response to fat was less consistent and more difficult to measure in the common bile duct, even 5 years after operation. It was concluded that not all patients with indications for exploration of the common bile duct on operative cholangiography show a dilatation response to fat on preoperative testing. Also, fatty meal sonography should be used with caution because the response to fat in asymptomatic patients soon after operation is unpredictable, with occasional patients showing dilation without apparent obstruction. Measurement of common hepatic duct is preferred to common bile duct and increases in diameter of 1 mm are probably not significant. PMID- 2210257 TI - The uncoupling of biliary lipid from bile acid secretion by organic anions in the rat. AB - A number of organic anions has been shown to inhibit biliary phospholipid and cholesterol secretion without affecting bile acid secretion. However, the mechanism of this uncoupling phenomenon is still unclear. This study shows a comparison of the effects of ampicillin (18 mumol/100g body wt), sulfated taurolithocholic acid (0.2 and 1.0 mumol/100 g body wt), and indocyanine green (0.6 mumol/100 g body wt) in control and Groningen Yellow-Wistar rats with chronic (8 days) biliary drainage. Groningen Yellow rats have a hereditary defect in hepatobiliary transport of various organic anions. Bile secretion, but not hepatic uptake, of the three organic anions was strongly impaired in Groningen Yellow rats compared with controls. Ampicillin and sulfated taurolithocholic acid caused a strong uncoupling in control rats but had no effect or a much smaller effect on lipid secretion in Groningen Yellow rats. Indocyanine green did not affect lipid secretion, in either control or in Groningen Yellow rats. Gel filtration chromatography of bile showed a specific coelution of ampicillin and sulfated taurolithocholic acid with the bile acid fraction, whereas indocyanine green coeluted with the phospholipid/cholesterol fraction. This study concludes that the uncoupling by ampicillin and sulfated taurolithocholic acid occurs after their secretion into bile and is caused by interaction of these compounds with bile acids. It is hypothesized that this interaction inhibits the capacity of bile acids to induce secretion of phospholipids and cholesterol into the bile. PMID- 2210258 TI - Characterization of bovine gallbladder mucin. Amino acid sequences of tryptic peptides from the glycosylated domain of the protein core. AB - Gallbladder mucin is a densely glycosylated macro-molecule that promotes cholesterol gallstone formation in experimental animals and in humans. Bovine gallbladder mucin structure was studied after chemical deglycosylation by treatment with anhydrous hydrogen fluoride at 23 degrees C for 3 hours. Deglycosylated mucin contained less than 5% of the amino sugar and neutral hexose content of native mucin. Electrophoretic and molecular sieve chromatographic analyses indicated that significant cleavage of the mucin polypeptide core had occurred during deglycosylation. Deglycosylated mucin was separated into three major fractions by reverse-phase chromatography, one of which was enriched with respect to threonine and proline. Tryptic peptides prepared from this fraction were purified by molecular sieve and reverse-phase chromatography, and the amino acid sequences (8-20 residues) of the four principal tryptic peptides were determined. These peptides contained 65%-75% threonine and proline residues and demonstrated 80%-100% sequence similarity. These data provide the first information on the primary structure of gallbladder mucin and suggest that repeating amino acid sequences occur in this protein. Comparison of gallbladder mucin peptide structure with the consensus repeat sequence of human intestinal mucin showed approximately 60% sequence similarity. It was concluded that mammalian gastrointestinal mucins may be derived from a common ancestral gene. PMID- 2210260 TI - Caliber-persistent artery of the stomach (Dieulafoy's vascular malformation). AB - Caliber-persistent artery of the stomach (also known as cirsoid aneurysm, Dieulafoy's lesion, and submucosal arterial malformation) is clinically manifested as recurrent, massive, often fatal hematemesis. The lesion often is not seen endoscopically. Left gastric angiography in one patient with hematemesis showed a convoluted and ectatic artery in the gastric fundus, which proved to be caliber-persistent artery of the stomach on pathological examination. The tortuosity of the abnormal vessel in this condition has been attributed to artefactual contraction of the stomach following excision and formalin fixation. This is the first reported case in which a pathologically proven lesion has been clearly visualized by angiography. This demonstrates that the submucosal vessel is truly and not artifactually sinuous. It is proposed that angiographic demonstration of a nontapering, convoluted artery in the territory of the left gastric artery is highly suggestive of caliber-persistent artery of the stomach. PMID- 2210259 TI - Resolution of inferior vena cava syndrome after embolization of a hepatic adenoma. AB - A 77-year-old man presented with severe pruritus and massive lower body edema. Computerized axial tomography of the abdomen showed a large hepatic mass compressing the inferior vena cava, and a liver biopsy specimen showed hepatic adenoma. Embolization of vessels feeding the hepatic tumor resulted in complete resolution of pruritus and ascites, and clinical remission has persisted for 1 year following partial obliteration of tumor vasculature. Angiographic ablation of tumor blood supply represents a nonoperative means for inducing clinical remission in patients with symptomatic hepatic adenoma who are at high surgical risk. PMID- 2210261 TI - Misdiagnosis of the Zollinger-Ellison syndrome due to hyperlipidemia. AB - Most authorities feel that diagnosis of the Zollinger-Ellison syndrome is established when the serum gastrin level is greater than 1000 pg/mL (1000 ng/L) in a patient with gastric acid hypersecretion and clinical manifestations consistent with the diagnosis. A patient with recurrent peptic ulcer disease is reported who was thought to have had the Zollinger-Ellison syndrome based on two serum gastrin level measurements greater than 1000 pg/mL (1000 ng/L). Subsequent evaluation revealed the gastrin elevation to be spurious because the sample was hyperlipidemic. Lipemic serum samples may yield falsely elevated serum gastrin determinations as determined by radioimmunoassay. PMID- 2210262 TI - Pemoline-associated hepatic injury. AB - Among 100 cases of hepatic injury attributed to the administration of pemoline, 43 had sufficient accompanying information to permit analysis. All but two patients were less than 20 years old, and 80% were less than 12 years old. Males predominated the study. Injury appeared as early as 1 week or as late as greater than 1 year of taking the drug. The injury was uniformly hepatocellular as judged by the high values for aminotransferases and by death in massive necrosis in one patient. Mechanism was judged to be idiosyncratic, and the idiosyncrasy was probably metabolic rather than immunologic. PMID- 2210263 TI - Reports from the NIH DDDN. The General Medicine A-2 Study Section. PMID- 2210264 TI - Acalculous cholecystitis: a new perspective. PMID- 2210265 TI - Acute cholangitis--endoscopic drainage or emergency surgery? PMID- 2210267 TI - Hemodynamic status during famotidine infusion. PMID- 2210266 TI - Differentiation of spontaneous from secondary bacterial peritonitis in cirrhotics. PMID- 2210268 TI - Geopathology of early gastric cancer. PMID- 2210269 TI - Is gastric acid hypersecretion the only reason for refractory gastroesophageal reflux disease? PMID- 2210270 TI - Can alcohol cause true acute pancreatitis? PMID- 2210271 TI - Lactulose hydrogen breath test in the diagnosis of bacterial overgrowth. PMID- 2210272 TI - Endosonography of peri-anal and peri-colorectal fistula and/or abscess in Crohn's disease. AB - Transcolorectal endosonography (ES) was performed in 36 patients with Crohn's disease suspected clinically to have a fistula or abscess. A hypoechoic or anechoic duct-like lesion immediately adjacent to the anorectal lumen compatible with a fistula was found in 32 patients. A communication between the fistulous tract and adjacent structures such as the skin, anal canal, or vagina was detected in all 32 patients. An anechoic cavity adjacent to or communicating with the fistula was visualized in 29 of the 36 patients. A fistula was visualized in the remaining seven patients with no evidence of an abscess. This anechoic cavity compatible with an abscess was surgically confirmed in 14 of 17 patients. We judged the extent and configuration of the abnormalities to be more clearly visualized by ES when results were compared with fistulography in five patients. There were no ES complications, and we conclude that ES is the preferred diagnostic procedure in patients with peri-rectal pathology because of the low risk of bacterial dissemination and low incidence of patient discomfort. Utilizing ES after non-surgical treatment was successful in 19 patients for documentation of the response to therapy. PMID- 2210273 TI - Push-enteroscopy for diagnosis of patients with gastrointestinal bleeding of obscure origin. AB - Push-enteroscopy using a disinfected colonoscope was performed on 39 patients with gastrointestinal bleeding of obscure origin. Our results show that: (1) A high percentage of patients (38%) have pathological lesions responsible for bleeding located in the distal duodenum and proximal jejunum, which are readily detected by push-enteroscopy. (2) Duodeno-jejunal arteriovenous malformations (AVMs) are the most common cause for bleeding, and these lesions can be conveniently cauterized through the endoscope. (3) An efficient sequence of steps for diagnosis of patients with this problem includes push-enteroscopy when the initial EGD and colonoscopy are normal followed by small bowel radiography. Mesenteric angiography and intraoperative enteroscopy can be reserved for patients with severe bleeding when push-enteroscopy and small bowel radiography are negative. We conclude that push-enteroscopy has an important role to play in the early assessment of patients with gastrointestinal bleeding of obscure origin. PMID- 2210274 TI - Endoscopic ultrasonography for the evaluation of smooth muscle tumors in the upper gastrointestinal tract: an experience with 42 cases. AB - Before surgery, 12 patients with suspected leiomyoma and 12 patients with suspected leiomyosarcoma were studied by endoscopic ultrasonography (EUS), computed tomography (CT), endoscopy, and barium swallow. The results were correlated with surgery and histology. Ten leiomyomas, one benign gastric ulcer, one carcinoid metastasis, eight leiomyosarcomas, two leiomyoblastomas, one mucus secreting adenocarcinoma, and one bronchial carcinoma were diagnosed. Eighteen additional patients suspected to have benign submucosal lesions by endoscopy and barium meal were treated non-surgically, and studied by EUS and CT. EUS was superior to other imaging techniques in the detection, staging, and follow-up of submucosal smooth muscle tumors because of clear imaging of the intramural abnormality and adjacent lymph nodes. PMID- 2210275 TI - Mechanical lithotripsy of common duct stones. AB - Over the past 8 years we have utilized various types of mechanical lithotriptors to crush common bile duct stones. The procedure was performed in 93 patients with an overall success rate of 94%. However, because many accessories were in a developmental stage, entrapment of stones was not always possible on the first attempt, and the procedure was repeated in some patients a second or third time. During the interim, while awaiting another attempt at lithotripsy, cholangitis was prevented by leaving a prosthesis in place. A variety of lithotriptor models from different manufacturers have proven effective. We recommend that endoscopists use these devices to rid the bile duct of retained stones. PMID- 2210277 TI - The role of ERCP in children and adolescents. AB - The diagnostic and therapeutic role of ERCP in 42 patients ranging from 1 to 19 years of age is discussed. ERCP provided useful additional information in 15 patients with biliary tract disease, 15 patients with pancreatic disease, and 9 patients with abdominal pain. The appropriate duct was cannulated in 95% of cases. Mild pancreatitis occurred in two patients after ERCP. Endoscopic papillotomy was successful in five patients. ERCP plays an important part in the investigation of unexplained biliary tract and pancreatic disease. It rarely demonstrates abnormal pathology in patients with otherwise unexplained abdominal pain. PMID- 2210276 TI - Endoscopic cholangiopancreatography in hepatic clonorchiasis--a follow-up study. AB - Cholangiographic changes of the biliary system in 16 patients with proven hepatic clonorchiasis, diagnosed by positive stool or bile ova isolates, were studied. All patients presented with epigastric pain. Other symptoms included jaundice in 31% (5 of 16) and fever in 12.5% (2 of 16). Praziquantel given at 25 mg/kg for three doses in 1 day were administered. Three consecutive stool tests were performed 3 months after treatment and were negative in 87.5% (14 of 16). ERCP studies were repeated at a mean interval of 31.6 months (range, 8 to 69 months). Measurements of the bile ducts on retrograde cholangiograms before and after treatment were compared using the paired Student's t test. Filling defects and blunting of the terminal bile ducts seen on the initial cholangiogram, interpreted as the presence of adult worms, disappeared after treatment. However, there was no significant change between pre- and post-treatment measurement of bile duct caliber. Bile duct dilation, irregularities, and ductal proliferation persisted despite eradication of the parasite. PMID- 2210278 TI - Can clinicians accurately assess esophageal dilation without fluoroscopy? AB - This study questioned whether clinicians could determine the success of esophageal dilation accurately without the aid of fluoroscopy. Twenty patients were enrolled with the diagnosis of distal esophageal stenosis, including benign peptic stricture (17), Schatski's ring (2), and squamous cell carcinoma of the esophagus (1). Dilation attempts using only Maloney dilators were monitored fluoroscopically by the principle investigator, the physician and patient being unaware of the findings. Physicians then predicted whether or not their dilations were successful, and they examined various features to determine their usefulness in predicting successful dilation. They were able to predict successful dilation accurately in 97% of the cases studied; however, their predictions of unsuccessful dilation were correct only 60% of the time. Features helpful in predicting passage included easy passage of the dilator (98%) and the patient feeling the dilator in the stomach (95%). Excessive resistance suggesting unsuccessful passage was an unreliable feature and was often due to the dilator curling in the stomach. When Maloney dilators are used to dilate simple distal strictures, if the physician predicts successful passage, he is reliably accurate without the use of fluoroscopy; however, if unsuccessful passage is suspected, fluoroscopy must be used for confirmation. PMID- 2210279 TI - Endoscopic appearance and significance of functional lymphangiectasia of the duodenal mucosa. AB - Intestinal lymphangiectasia is found in a wide variety of pathologic conditions. Functional lymphangiectasia has not been well characterized. We report 20 patients followed for 9 to 55 months (mean 30 months) after incidental detection at endoscopy of lymphangiectasia. Our study indicates that functional lymphangiectasia is not pathologic and does not warrant repeat endoscopy in the absence of other clinical indications. PMID- 2210281 TI - Colonic endoscopic ultrasonography: first results of a new technique. PMID- 2210280 TI - Adequacy of disposable biopsy forceps for gastrointestinal endoscopy: a direct comparison with reusable forceps. AB - Disposable plastic biopsy forceps were compared prospectively to reusable stainless steel forceps. Thirty consecutive patients underwent a total of 249 biopsies, 124 with the disposable forceps, and 125 with reusable forceps. Biopsy locations included the esophagus, stomach, small intestine, colon, and common bile duct. Specimens were compared microscopically to determine overall surface area, depth, adequacy, and diagnostic result. The disposable biopsy forceps yielded specimens which were 37% smaller when compared with the reusable forceps. In five of the comparisons, minor differences in histological findings were noted between the two groups of biopsy specimens, but these differences did not alter the pathological diagnosis. However, in three cases in which superficial specimens were obtained, an underlying carcinoma was missed with the disposable forceps. Our study documents the utility of disposable biopsy forceps for mucosal lesions. In addition, there were 11 mechanical failures in 38 biopsy attempts with the plastic biopsy forceps. These forceps appear to be limited in their capacity to obtain adequate specimens from firm tissue or when submucosal biopsy samples are required, and they will require refinements in design to duplicate specimen quality obtained by traditional reusable forceps. Disposable forceps are particularly suitable for biopsy of mucosal lesions in patients with possible communicable disease, and they should help to reduce cross-contamination in the gastroenterology laboratory. PMID- 2210282 TI - Cannulation of the biliary tree, cystic duct and gallbladder using a hydrophilic polymer-coated steerable guide wire. PMID- 2210283 TI - Documentation of fluoroscopic and endoscopic images using a color video printer. PMID- 2210284 TI - Inflammatory double-barrelled esophagus in two patients with AIDS. PMID- 2210285 TI - Compact parakeratosis of esophageal mucosa: a non-specific lesion mimicking "leukoplakia". PMID- 2210286 TI - Bipolar electrocoagulation for watermelon stomach. PMID- 2210287 TI - Removal of intrahepatic stone by rigid ultrasonic lithotripter through a choledochotomy tract. PMID- 2210289 TI - Endoscopic excision of a foreign body in the pyloric channel. PMID- 2210288 TI - Endoscopic diagnosis of the Panje prosthesis in a patient with upper esophageal stricture. PMID- 2210290 TI - The pseudo-double duct sign: an ERCP finding in pancreatic carcinoma. PMID- 2210292 TI - Endoscopic radio frequency electrosurgery. PMID- 2210293 TI - British endoscopy: recent highlights. PMID- 2210291 TI - ERCP in the diagnosis of ductectatic mucinous cystadenocarcinoma of the pancreas. PMID- 2210294 TI - Sedation for upper gastrointestinal endoscopy: time for reappraisal? PMID- 2210295 TI - Delayed hemorrhage following "hot biopsy" of a diminutive colonic polyp. PMID- 2210296 TI - Endoscopic computer repair. PMID- 2210297 TI - Minnesota tube placement using a guide wire. PMID- 2210298 TI - Nodular lymphoid hyperplasia of the colon in adults: is it common? PMID- 2210299 TI - Shifting blue hue sign. PMID- 2210300 TI - A protective shield for the endoscopist. PMID- 2210301 TI - The disappearing penny. PMID- 2210302 TI - Present day indications for nasobiliary drainage. PMID- 2210303 TI - Necrotizing fasciitis--a complication of "successful" endoscopic sphincterotomy. PMID- 2210304 TI - Intraperitoneal hemorrhage from injury to the gastroepiploic artery: a complication of endoscopic retrograde sphincterotomy. PMID- 2210305 TI - Common hepatic duct perforation: a rare complication associated with ERCP. PMID- 2210309 TI - [The value of curettage in the assessment of abnormal uterine bleeding]. AB - Current practice of investigating abnormal uterine bleeding via dilatation and curettage is sometimes open to question, and outpatient procedures are emphasised. The therapeutic effect of curettage in normalising menstrual patterns is being discussed. In a prospective study we answered the question of diagnostic and therapeutic effects of curettage. Over a period of 6 months, all patients with curettage treated in our department were investigated (history, risk factors, previous hormonal treatment, preoperative haemoglobin value, type of anaesthesia, complications, histology). Curettages performed for the purpose of abortion, as well as in combination with conisation of the uterine cervix, were not included in the study. 234 curettages were carried out. Clinical indications were as follows: in 29% of the cases recurrent preclimacteric metrorrhagia, in 27% climacteric metrorrhagia, in 24% PMB (postmenopausal bleeding). In 19 cases we found an Hb value lower than 10.5 g%. Risk factors (obesity, hypertension, diabetes mellitus) for endometrial cancer were found in 38% of MB and in 20% of climacteric metrorrhagia. In 9 cases, the histological diagnosis was endometrial cancer (clinical indications: 5 PMB, 3 climacteric metrorrhagia, 1 recurrent preclimacteric metrorrhagia). Our study shows, that the indication for curettage should be applied generously, especially in cases of abnormal postmenopausal and perimenopausal bleeding. PMID- 2210306 TI - [Immunohistochemistry in the diagnosis of gynecologic neoplasms]. AB - This survey presents the practical application of immunohistochemistry additional to clinical anamnesis and histology (HE staining) in the differential diagnosis of morphologically similar lesions. First of all, the algorithmic approach for immunohistological diagnosis of undifferentiated or non-classifiable malignant neoplasias of the female genital tract is described and the significance of immunohistochemistry for the differential diagnostic discrimination and the histogenesis of organ-specific gynaecological neoplasias is re-assessed. PMID- 2210308 TI - [Incidence of secondary tumors following cervical neoplasia in Saarland 1968 1987]. AB - In 4468 patients diagnosed with invasive cancer or carcinoma in situ of the uterine cervix in Saarland/W-Germany in 1968-1987, 149 secondary cancers were observed compared to 150.6 which would have been expected had the same risk prevailed as in the general population (SMR = 0.99, 95% confidence interval 0.84 1.17). There were, however, substantial differences between the relative risks for specific cancer sites. For example, the risk of breast cancer was clearly lower than in the general population (SMR = 0.62, 95% confidence interval 0.43 0.88), while the risk of cancer of the urinary bladder was significantly increased (SMR = 2.88, 95% confidence interval 1.53-4.93). The results are consistent with findings from other countries, with current knowledge of risk factor profiles of different malignancies and with hypotheses on possible side effects of radiotherapy. PMID- 2210307 TI - [Treatment of primary cancer of the fallopian tube]. AB - 33 patients treated since 1970 at the Medical School of the University of Graz, were classified using the FIGO system for ovarian carcinoma, fourteen were in stage I, 8 stage II, 8 stage III and 3 stage IV. In 17 patients, surgery consisted of total abdominal or vaginal hysterectomy with bilateral salpingo oophorectomy; 12 patients underwent additional pelvic +/- paraaortic lymph node extirpation and in 4 the tumour excision was incomplete. Treatment in 6 patients was surgery alone (2/stage I, 4 with advanced disease) (Group A). Adjuvant radiotherapy was performed in 14 patients (Group B); the remaining patients were treated with single (2/13) or multiple agent chemotherapy (11/13) (Group C). The 3-year survival rate was 55% for stage I, 42% for stage II; 10/11 of the stage III/IV patients died within 26 months. The 4-year actuarial survival rate for group B was 68%, for group C 11%. There was no difference between the short-time results of stage II tumours when comparing radiotherapy against chemotherapy. The tumour progression rate was 60%, indicating the need for radical surgery as well as for more aggressive adjuvant treatment. Surgery alone is recommended for stage I disease confined to the mucosa. More advanced disease (extension to the serosa, stage Ic, stage II) requires whole abdominal irradiation with a boost to the pelvic lymph nodes. For stage III/IV tumours a multi-modality treatment is recommended. Chemotherapy (cis-platinum, cyclophosphamide) for recurrent disease resulted in remission in some cases. PMID- 2210310 TI - [Does vascularization of the fetal placenta modify end-diastolic blood flow velocity in umbilical arteries? A histometric contribution to the validation of Doppler ultrasound]. AB - The foetal intravillous blood volume was approximately determined in 90 cases, using placental histiometry post partum. This was compared with the Doppler sonographic flow patterns in the umbilical arteries determined during the last week ante partum. A direct dependence was seen: The larger the peripheral vascular tree of the placenta fetalis, the lower the resistance against the blood flow in the umbilical artery, i.e. the higher the enddiastolic blood flow velocities and vice versa. There is a highly significant correlation between the foetal intravillous blood volume and the foetal risks of Caesarean section performed, because of intrauterine asphyxia, growth retardation or reduced foetal outcome. PMID- 2210311 TI - [Magnesium, calcium, hemoglobin, hematocrit, estriol and human placental lactogen with magnesium substitution in pregnancy]. AB - In a randomised double-blind study 568 women were given orally either 15 mmol magnesium-aspartate hydrochloride per day or aspartic acid as placebo. The outcome of pregnancy was significantly improved in the magnesium group (fewer maternal hospitalisations, reduction in preterm delivery and less frequent referral of newborn to the neonatal intensive care unit). In the 437 patients with regular intake of tablets, haematocrit, haemoglobin and calcium show a decrease up to 20 weeks of gestation (wks) and an increase during the last 8 wks, whereas magnesium stays at a low level. Oestriol and HPL are rising steadily during gestation. In all parameters, no differences were found between the magnesium and placebo group, except for a higher level of oestriol at 33 to 36 wks and a lower level above 36 wks in the magnesium group. Because of the numerous benefits throughout the pregnancy magnesium supplementation is recommended for all pregnancies. PMID- 2210313 TI - [Prenatal diagnosis of a sacrococcygeal teratoma with hydrops fetalis and placental hypertrophy--consequences for the further course of pregnancy]. AB - A fetal sacrococcygeal teratoma may cause hypertrophy of the placenta and fetal hydrops. This is dangerous for the fetus and also for the mother. The maternal risk results from preeclampsia and respiratory insufficiency, associated with elevated beta-HCG. In that case, pregnancy should be terminated by caesarean section due to maternal reasons. PMID- 2210314 TI - [Androgenization in postmenopause in rare ovarian tumors--2 case reports]. AB - Androgen-producing tumours of the ovary are uncommon in postmenopausal women. We report on symptoms of two patients with androgenization due to a stromal-Leydig cell tumour and a steroid-cell tumour, respectively. Clinical signs and symptoms, laboratory findings and therapeutic consequences are discussed. PMID- 2210312 TI - [Effect of sequential embryo transfer on pregnancy following in vitro fertilization]. AB - In this study, the influence of sequential embryo transfers in an in-vitro fertilisation programme was examined. After in-vitro fertilisation, a maximum of 6 fertilised oocytes were cultured. In cases with more than 6 fertilised oocytes, the rest was cryopreserved in the pronucleus stage. At day 2 after an oocytes retrieval, three embryos with the best morphological appearance were replaced and the remaining embryos (1-3) were cultured for further 3 days. At day 5 after oocytes collection, second a embryo transfer was performed, if one of these embryos had reached the blastocyst stage. In a total of 106 patients, 40 pregnancies (38%) could be observed. No statistical difference in the pregnancy rate could be seen between the group with a second embryo transfer (n = 38; 42%) and the group without second transfer (n = 68; 35%). The incidence of multiple pregnancy was not statistically different between both group and no high-rank multiple pregnancy (greater than Triplete) were observed. Out of 300 cultured embryos, only 59 embryos (17%) reached the blastocyst stage. In the group, in which a second embryo transfer was performed, 22 patients received one blastocyst and 13 patients two blastocysts during the second transfer. The second transfer did not have a significant effect on the pregnancy rate in this series. The most important factor for the induction of pregnancy seems to be the quality of the embryos transferred on day 2 following oocyte retrieval. PMID- 2210315 TI - [Study of isoenzymes of lymphocyte populations during controlled immunization and in autoimmune pathology]. AB - It has been shown that during immune system activation pronounced alterations are observed in the metabolic process course in lymphoid cells that, probably, reflect the changes in T- and B-lymphocyte functional activity, and the kinetics of intercellular relationships. The ratio of LDH1 and LDH5 fractions most differing in electrophoretic mobility has been recommended as a sign of B-system immunity activation. PMID- 2210317 TI - [Quantitative evaluation of latent gastrointestinal hemorrhage in patients with iron deficiency anemia (preliminary report)]. AB - Radiologic investigation of concealed gastro-intestinal hemorrhage with 51Cr was conducted for its detection and quantitative estimation in 102 patients with iron deficiency anemia (IDA), loss of blood from the digestive tract was detected in 52 of them. A definite relationship was noted between the volume of hemorrhage and the disease responsible for the development of IDA. Moderate hemorrhage from 2.5 to 15.0 ml/day was detected in chronic inflammatory diseases of the gastro intestinal tract (GIT): chronic gastritis, colitis. High volumes of hemorrhage are characteristic of diseases attended by gross changes in the digestive tract: polyps, tumors, diverticula, varicosis in GIT. It has been shown that the radiologic method of quantitative estimation of concealed gastro-intestinal hemorrhage with the use of 51Cr is highly sensitive and accurate, that permitted the authors to recommend this method for both practical and scientific investigations. PMID- 2210316 TI - [Rheological properties of erythrocytes and hemostasis in patients with acquired autoimmune hemolytic anemia treated with anti- lymphocyte globulin]. AB - Rheologic properties of red blood cells and hemostasis were studied in patients with acquired autoimmune hemolytic anemia who received antilymphocytic globulin (ALG). Hypocoagulation changes attended by elevation of red blood cell aggregation activity were detected in the patients already at their admission to the hospital. After administration of ALG, growth of these shifts, characteristic of disseminated intravascular blood coagulation (DIC) syndrome, was noted. It was shown that erythrocytic thromboplastin and antiheparin factor action on blood coagulation, mainly at the expense of the young cell fraction, was responsible for disorders in hemostasis. Nevertheless, despite the presence of DIC syndrome, in the group of patients, who received ALG, no clinical signs of this state were recorded, that could be explained by the protective effect of red blood cell intensified capacity for aggregation leading to the improvement of blood coagulation parameters. PMID- 2210318 TI - [Lipid composition of erythrocytes in iron deficiency anemia]. AB - The assay of lipid composition in red blood cells of 51 patients with iron deficiency anemia (IDA) was conducted with the use of horizontal thin-layer chromatography, and the state of the end blood flow was studied with the ai of conjunctival biomicroscopy. It was found that in IDA patients the content of total lipids, phospholipids, free fatty acids, cholesterol, sphingomyelins, cardiolipins and phosphatidic acids increased and that of triglycerides decreased. The content of the rest fractions of total lipids in IDA patients was practically not changed. Variations in lipid composition of red blood cells lead to disorders in their functional activity. In IDA patients it is clinically expressed in the development of the sludge phenomenon that aggravates tissue hypoxia in women with this disease. PMID- 2210319 TI - [Study of iron metabolism in chronic diffuse diseases of the liver]. AB - Iron metabolism was studied in patients with chronic diffuse diseases of the liver. A sharp increase of ferritin content at the expense of its release from affected hepatocytes, and formation of antibodies to ferritin of the splenic type have been recorded in patients with cirrhosis of the liver. The observed growth of ferritin content in red blood cells can be explained by functional deficiency of red blood cells and by the presence of hemolytic process (twofold decrease of haptoglobin level). A conclusion has been made that ferritin content in the blood serum does not correlate with the total iron reserves, and serum ferritin level should be considered not as a sign of the pathologic process, but as an index of iron reserves capable of participating in metabolic processes. PMID- 2210321 TI - [Changes in cytospectrophotometric characteristics and configuration of erythrocytes exposed to constant electric current]. AB - The action of constant current (0.01-3 A, 1-25 V) on human blood during varying exposures induced intensified plaque-formation in the preparations of the local hemolysis test, and transformation of red blood cells-discocytes into echino- and poikilocytes that was attended by pronounced changes in the extent, intensity of light diffusion, natural green and red luminescence of red blood cells caused by flavoproteins and metalloporphyrins. The growth of the last factor has evidenced the presence of significant destructive changes in the cells as a result of constant current direct action on red blood cells. PMID- 2210320 TI - [Morphofunctional status of blood and bone marrow cells in acute experimental hepatitis induced by allyl alcohol]. AB - Acute experimental hepatitis was induced by a single injection of 1% water solution of allyl spirit in a dose of 100 mg/kg. Morphofunctional state of peripheral blood and bone marrow cells was studied with the use of hematological and cytochemical methods. Specific changes were detected in the peripheral blood and bone marrow cell parameters in the early (6 and 12 h) and late (24h--10 days) periods after the injection. Changes in the liver and in the blood and bone marrow cells were irreversible. Most of the parameters studied returned to normal 22 days after the injection of allyl spirit. PMID- 2210322 TI - [Effect of heparin on erythrocyte damage in various toxicogenic DIC syndromes]. AB - In experiments in vitro it has been established that heparin does not have a direct hemolyzing action, but it significantly reduces red blood cell resistance to acid. In experiments in vivo heparin significantly intensifies red blood cell resistance to the action of acid hemolytics. Hemolysis during intoxication with the toxins studied is, to a greater extent, secondary in relation to the intravascular blood coagulation. PMID- 2210323 TI - [Nonspecific immunity]. PMID- 2210324 TI - [Characteristics of homeostasis in blood and plasma donors]. PMID- 2210326 TI - [Possible changes in the technique of indirect Coombs' reaction]. PMID- 2210325 TI - [Effect of various socio-biological and immunogenetic factors on the intensity of antibody formation in blood donors immunized with adsorbed staphylococcal anatoxin with different degree of immunogenicity]. PMID- 2210328 TI - [Blood coagulating and anticoagulant properties of the tissues in experimental chronic alcoholism in albino rats]. AB - A study was made of thromboplastin, antiheparin and antithrombin activity of the brain, heart and liver tissues of rats in experimental chronic alcoholization. Appreciable changes in the tissue factors of coagulation according to the dyscoagulemia type depending on the duration and gravity of alcoholic intoxication may aggravate hemostatic disorders. PMID- 2210327 TI - [Activation of lipid peroxidation in erythrocytes during blood coagulation in vitro]. AB - A comparative investigation of antioxidant enzyme activity and lipid hydroperoxide concentration in red blood cells of the whole and anticoagulant containing blood of 33 donors was conducted to elucidate the causes of increasing the permeability of red blood cell membrane during blood coagulation in vitro. It has been shown that one of the causes of intensified red blood cell peroxidation during blood coagulation is a disturbed ratio of superoxide dismutase and catalase activities leading to a decrease in the antioxidant enzymatic protection. PMID- 2210329 TI - DNA analysis of intracellular Campylobacter-like organisms associated with the porcine proliferative enteropathies: novel organism proposed. AB - Intracellular Campylobacter-like organisms are a consistent feature of the porcine proliferative enteropathies. The relationship between these organisms and known Campylobacter sp. previously associated with the disease was studied using restriction enzyme analysis and DNA-DNA blot hybridization techniques. BglII restriction enzyme fragment patterns of DNA of the Campylobacter-like organisms were fundamentally different from those of C. mucosalis, C. hyointestnalis, C. jejuni, and C. coli. Crude DNA preparations from Campylobacter-like organisms hybridized strongly with homologous preparations, weakly with porcine DNA and not at all with DNA from Campylobacter sp. Fragment specific DNA probes prepared from Campylobacter-like organisms only hybridized with homologous preparations. This work suggests that the intracellular Campylobacter-like organisms are not one of the known Campylobacter sp. It is possible that they are a novel, uncultured organism worthy of a new name, such as HC. intracellulare'. PMID- 2210332 TI - Antifungal drugs affect adherence of Candida albicans to acrylic surfaces by changing the zeta-potential of fungal cells. AB - The effect of sub-inhibitory concentrations of antifungal drugs on the adherence of Candida albicans to acrylic surfaces was investigated. Among five antifungals tested, azalomycin F and aculeacin A significantly enhanced the adherence. The zeta-potential of fungal cells was affected by antifungal drugs, whereas no significant change in cell surface hydrophobicity was observed. The relationship obtained between the change in the adherence and that in zeta-potential suggests that the enhanced adherence was caused by decreased electric repulsive forces. PMID- 2210331 TI - sulA-independent division inhibition in his-constitutive strains of Salmonella typhimurium. AB - Constitutive expression of the S. typhimurium histidine operon causes multiple phenotypic changes including strong filamentation. However, the SOS regulatory network is not involved in the inhibition of cell division. The possibility of SOS-independent activation of sulA gene transcription has been ruled out using sulA-lacZ fusions. These results suggest the existence of a pathway of division inhibition unrelated to sulA and not regulated by the SOS system. PMID- 2210334 TI - Characterization of extracellular peroxidases produced by acetate-buffered cultures of the lignin-degrading basidiomycete Phanerochaete chrysosporium. AB - Growth of Phanerochaete chrysosporium in a nitrogen-limited medium buffered with sodium acetate, instead of the commonly used 2,2-dimethylsuccinate (DMS), resulted in quantitative and qualitative differences in the production of various extracellular lignin peroxidases (LIPs) and manganese-dependent peroxidases (MNPs) involved in lignin degradation. The results indicate that production of LIPs and MNPs can be selectively enhanced by manipulation of culture conditions. Partial N-terminal analyses of the major LIPs and MNPs have made it possible to assign a specific protein to the specific genes and cDNAs that have been reported recently. The LIPs and MNPs differed widely in their ability to decolorize various dyes that are known to be degraded by the lignin degrading enzyme system of P. chrysosporium. PMID- 2210335 TI - Cloning and structure of the pyrE gene of Lactobacillus plantarum CCM 1904. AB - The pyrE gene of Lactobacillus plantarum CCM 1904, coding for the orotate phosphoribosyl transferase involved in the pyrimidine biosynthetic pathway, was cloned in Escherichia coli and sequenced. The predicted polypeptide sequence extending over 212 amino acids (MW 22,690) was compared to those of E. coli and to those of lower eukaryotes (Saccharomyces cerevisiae, Podospora anserina, Sordaria macrospora, Dictyostelium discoideum). Important conserved stretches were revealed, implying that these proteins are closely related. PMID- 2210336 TI - Effects of sinefungin and S-adenosylhomocysteine on DNA and protein methyltransferases from Streptomyces and other bacteria. AB - Sinefungin is a naturally occurring nucleoside isolated from cultures of Streptomyces griseolus and S. incarnatus. It is structurally related to S adenosyl-methionine (SAM) and S-adenosyl-L-homocysteine (SAH). Its effect and level of action on prokaryotes has not been studied with the same detail as with eukaryotic cells. In this report we describe the effect of sinefungin and SAH on several Streptomyces methyltransferases (DNA and protein MTases) and on other bacterial DNA-MTases. Protein MTases are resistant to sinefungin, whereas DNA MTases are inhibited. Adenine MTases however, seem more sensitive to this analogue than cytosine MTases. PMID- 2210337 TI - Change of a single amino acid in the leader peptide of a staphylococcal beta lactamase prevents the appearance of the enzyme in the medium. AB - A plasmid encoded beta-lactamase gene from Staphylococcus aureus (strain 3804) was cloned and sequenced. The nucleotide sequence is very similar to those obtained for other such beta-lactamase genes. The beta-lactamase has an N terminal region characteristic of an exported protein and assay of activity shows that the enzyme is found extracellularly in S. aureus. A residue in the N terminal region near to the postulated cleavage site was changed by site-directed mutagenesis from a serine into a proline. Comparison of beta-lactamase activity outside the cell in strains containing the cloned wild-type and mutagenised genes shows that this single amino acid completely prevents the appearance of the enzyme in the medium. PMID- 2210330 TI - Separation of plasmid-mediated extended spectrum beta-lactamases by fast protein liquid chromatography (FPLC system). AB - We have devised a reliable procedure for the separation of three beta-lactamases of isoelectric focusing points (pI), 5.4, 6.5, and 7.9 by Fast Protein Liquid Chromatography (FPLC System). All of these enzymes were transferable and originated from a ceftazidime and cefotaxime resistant Klebsiella pneumoniae isolated in Bombay, India. The complete separation of the enzymes, achievable by this method, allowed each of the different individual beta-lactamases to be characterized biochemically. This analysis revealed that the enzymes of pI 6.5 and pI 7.9 hydrolysed ceftazidime and cefotaxime, and were responsible for the resistance of K. pneumoniae, and its Escherichia coli J53-2 transconjugant to third generation cephalosporins. The enzyme of pI 5.4 was the TEM-1 beta lactamase. The beta-lactamase of pI 7.9 appears quite different from any previously reported third generation cephalosporin hydrolysing beta-lactamase, and consequently given the preliminary designation DJP-1. This is also the first example of extended spectrum hydrolysing beta-lactamases found in Asia. PMID- 2210333 TI - Characterization of an unglycosylated low molecular weight 1,4-beta-glucan glucanohydrolase of Trichoderma reesei. AB - A low molecular weight endoglucanase (1,4-beta-glucan glucanohydrolase E.C.3.2.1.4) was purified to homogeneity by a two-step procedure from 7 day old culture filtrates of Trichoderma reesei. The endoglucanase was obtained by BioGel A 0.5 m gel chromatography followed by preparative PAGIF. The purified endoglucanase was homogeneous upon titration curve separation. Enzyme characteristics were: Mr 25 kDa, pI 7.5. The amino acid composition is predominantly neutral (mainly glycine). The N-terminus is arginine. The pH optimum for this endoglucanase was 5.8 and its optimal temperature was at 52 degrees C. The activity of this endoglucanase gave a strong increase in CMC fluidity with only a small release of reducing sugars. The endoglucanase was 0.2% of total culture medium protein content. The reducing sugars upon CMC digestion were G1-G4. The enzyme had no specificity towards crystalline cellulose (Avicel) or xylan. The endoglucanase is not a glycoprotein. PMID- 2210338 TI - Influence of respiratory substrate on the cytochrome content of Shewanella putrefaciens. AB - Shewanella putrefaciens can use trimethylamine oxide (TMAO) as electron acceptor under anoxic conditions. The associated cytochromes induced during growth under various respiratory conditions have been separated by liquid chromatography (DEAE Sepharose CL6b) and SDS-PAGE and characterized spectrophotometrically and by redox potentiometry. Two major low potential cytochromes and at least three minor low potential cytochromes, likely to be involved in TMAO reduction, were found. No cytochrome specific for TMAO reductase was found. PMID- 2210342 TI - Expression of the lipase gene from Staphylococcus hyicus in Lactobacillus curvatus Lc2-c. AB - An electroporation based transformation system was developed for Lactobacillus curvatus Lc2-c, a plasmid cured potential raw sausage starter. It was transformed with plasmid pLipPS1, a staphylococcal vector plasmid containing the lipase gene from Staphylococcus hyicus. Transformants exhibited high lipase activity, whereas the wild type strain was lipase negative. The production and release into the medium of a heterologous lipase by a Lactobacillus could be shown for the first time. PMID- 2210340 TI - Isolation and characterization of bacteriophage PM3 from Aeromonas hydrophila the bacterial receptor for which is the monopolar flagellum. AB - PM3 is an Aeromonas-specific bacteriophage which was isolated and characterized on A. hydrophila strain TF7. Spontaneous mutants resistant to PM3 were non-motile having lost their characteristic monopolar flagellum. In addition, purified flagella inactivated PM3. PM3 is the first filamentous bacteriophage isolated on Aeromonas, the adsorption site for which is the monopolar flagellum. PMID- 2210339 TI - Direct observations of cooperative effects in oral streptococcal adhesion to glass by analysis of the spatial arrangement of adhering bacteria. AB - The spatial arrangement of two strains of oral bacteria adhering on glass was studied in order to investigate cooperative effects in their adhesion mechanisms. Streptococcus salivarius HB was a strain which possessed several classes of fibrillar surface appendages, whereas on the cell surface of S. mutants NS no surface appendages could be identified. The bacteria were deposited from a flowing suspension with various buffer concentrations on the bottom glass plate of a parallel plate flow cell and were observed directly with a video camera mounted on a phase contrast microscope. The positions of all adhering bacteria were determined by means of automated real time image analysis and subsequently employed for calculating radial and angular pair distribution functions. Pair distribution functions indicate the average relative number density of bacteria around one deposited bacterium as a function of the radial distance or the angular orientation relative to the flow direction. From the calculated pair distribution functions of both bacterial strains it was concluded that cooperative effects contributed to the adhesion of S. salivarius HB, but not to adhesion of S. mutants NS. It was suggested that these cooperative effects originate from the surface appendages of S. salivarius HB. PMID- 2210341 TI - Membrane potential of Plasmodium falciparum gametocytes monitored with rhodamine 123. AB - The membrane potential of Plasmodium falciparum gametocytes was monitored with the cationic permeant fluorescent dye rhodamine 123 (R123) as a probe. Epifluorescence microscopy revealed that R123 at 1 microgram/ml rather selectively partitioned into structure resembling large mitochondria. Treatment of R123-loaded gametocytes with various inhibitors including those of respiration resulted in disappearance of fluorescence from what appeared to be the mitochondria, but not from the cytosol. These results indicate that P. falciparum gametocytes have the mitochondrion maintaining an inside negative membrane potential. PMID- 2210343 TI - Comparison of coligenoid formation by B subunits of porcine and human Escherichia coli heat-labile enterotoxins. AB - A hybrid B subunit (coligenoid) of heat-labile enterotoxin could not be made from human heat-labile enterotoxin B subunit(LTh-B) and porcine LTp-B subunit(LTp-B). LTp-B monomer was able to form coligenoid by reassociation with homologous LTp-B monomer, but not with heterogeneous LTh-B monomer and vice versa. The dissociation of both coligenoids into monomers by SDS treatment occurred in a time-dependent manner, but the dissociation of LTh-B colligenoid was faster than that of LTp-B coligenoid. The association of LTp-B monomer is tighter than that of LTh-B monomer. The pI values of LTp-B coligenoid, LTp-B monomer and denatured LTp-B monomer were similar at 9.6-9.8, while the pI values of LTh-B coligenoid, LTh-B monomer and denatured LTh-B monomer were determined as 5.6-5.8, 9.2-9.6 and 9.2-9.6, respectively. All the ionic amino acids of LTp-B exist on the coligenoid surface. The difference in pI values between LTh-B coligenoid and LTh-B monomer suggests that some basic amino acids are located within the LTh-B coligenoid complex, but are exposed in the LTh-B monomer. These data suggest that the 4 amino acid substitutions between LTh-B and LTp-B result in a three dimensional structure difference and a less stable formation of LTh-B coligenoid compared to LTp-B coligenoid. PMID- 2210344 TI - Dioxygenolytic cleavage of aryl ether bonds: 1,2-dihydro-1,2-dihydroxy-4 carboxybenzophenone as evidence for initial 1,2-dioxygenation in 3- and 4-carboxy biphenyl ether degradation. AB - A bacterial strain, Pseudomonas sp. POB 310, was enriched with 4-carboxy biphenyl ether as sole source of carbon and energy. Resting cells of POB 310 co-oxidize a substrate analogue, 4-carboxybenzophenone, yielding 1,2-dihydro-1,2-dihydroxy-4 carboxy-benzophenone. The ether bond of 3- and 4-carboxy biphenyl ether is cleaved analogously by initial 1,2-dioxygenation, yielding a hemiacetal which is hydrolysed to protocatechuate and phenol. These intermediates are degraded via an ortho and meta pathway, respectively. Alternative 2,3- and 3,4-dioxygenation can be ruled out as triggering steps in carboxy biphenyl ether degradation. PMID- 2210346 TI - Significance of psychiatric symptoms in general medical patients with mood disorders. AB - Little difference was found between the psychiatric symptoms of medical patients and general-population subjects with affective disorder, both groups having been assessed with the same procedure (Present State Examination). Discrimination between medical patients with and without affective disorder was best achieved when patients with depressive and anxiety disorders were considered separately. Depressed mood, morning depression, and hopelessness were the key symptoms in the depressives, and nervous tension, free-floating anxiety, panic attacks, and specific phobias in the patients with anxiety disorders. Symptom profile did not distinguish patients with persistent affective disorders from those whose disorders had resolved at a 4-month follow-up. PMID- 2210345 TI - Identification of catalase negative/weak Campylobacter jejuni from human blood and faecal cultures by numerical analysis of electrophoretic protein patterns. AB - Twenty-eight isolates of catalase-negative/weak (CNW) thermophilic campylobacters from human blood and faecal cultures were characterized by one-dimensional (1-D) high-resolution SDS-PAGE of cellular proteins. A further 11 Campylobacter strains were included for reference purposes. Partial protein patterns were used as the basis for numerical analysis, which showed that all of the hippurate-positive strains had a high similarity to C. jejuni. Two subclusters were formed within C. jejuni corresponding to C. jejuni subsp. doylei (15 strains) and C. jejuni subsp. jejuni (4 strains). Most of the paediatric strains from South Africa were members of C. jejuni subsp. doylei. Hippurate-negative CNW thermophilic strains were identified as "C. upsaliensis". The analysis demonstrated that the catalase negative C. jejuni strains were quite distinct from "C. upsaliensis" and that electrophoretic protein patterns provide an excellent criterion for the identification of subspecies within C. jejuni. PMID- 2210347 TI - Factors affecting length of stay in a psychiatric intensive care unit. AB - As a response to the challenge posed by an increasing number of agitated and violent patients, there is in Canada a growing number of psychiatric intensive care units (PICUs), in both general and psychiatric hospital settings. In this article, the functioning of such a unit in a general hospital context is reviewed. Statistically significant changes in average length of stay (LOS) were observed, with an increase from 5.8 to 7.3 days over the period studied. The factors influencing the functioning and LOS of this PICU are analyzed. A possible "deskilling" of the staff in other wards is discussed, and alternative explanations are hypothesized in an attempt to shed light on the interaction between this unit and its environment. PMID- 2210348 TI - "Superwarfarin" ingestion. A new problem in covert anticoagulant overdose. AB - For the attention of psychiatric consultants, brodifacoum, a new longer-acting, warfarin-like oral anticoagulant rodenticide, has been used for suicide attempts. The overdose potential with brodifacoum is serious since it is readily available without prescription, and bleeding complications last for weeks to months after a single ingestion. This article reports a case of ingestion and reviews four similar cases from medical literature. Also reviewed are details about mechanism of action, procedures for diagnosis, and treatment requirements. Also, characteristics of persons who ingest long-acting anticoagulants appear to differ from those who ingest short-acting anticoagulants reported from earlier literature. PMID- 2210349 TI - Psychogeriatric consultation. General Hospital versus home for the aged. AB - As more elderly persons are institutionalized in long-term care settings, there will be an increasing need for psychiatric consultation-liaison (C/L) services. An understanding of how patterns of C/L service provision differ in these settings from those in the general hospital is important for efficient use of resources. In this study, certain characteristics of psychiatric consultations for the elderly patients in a general hospital were compared to consultations in a home for the aged. Three groups of 30 patients were examined: patients age 60 and over in a general hospital (GH), patients under age 60 in a general hospital (GHY), and patients in a home for the aged (HA). GH and GHY shared many characteristics, but there were significant differences between HA and GH: Consultations for HA were less likely to be urgent and more likely to be for management. Dementia was diagnosed in 70% of HA versus 27% in GH. Types of interventions were similar in GH and HA except that more psychotherapy was done in HA. In HA more contact was made with allied health professionals, while in GH there was more contact with medical personnel. GH patients were seen more intensively during the first 2 weeks following referral. We conclude that the major part-time attendance of a psychiatrist skilled in both the behavioral management of demented patients and liaison with allied health professionals is likely to be sufficient in long-term care institutions for elderly patients. However, the psychiatrist must also be proficient in the education of the staff of the institution so as to encourage the referral of all those patients who require psychiatric attention. PMID- 2210350 TI - Pain insensitivity in schizophrenia. Case report and review of the literature. AB - We describe a schizophrenic man whose lack of pain and related objective signs of a perforated small bowel led to a delay in diagnosis and surgical intervention. A review of the literature suggests that both psychodynamic and specific biologic factors can produce atypical presentations in psychotic patients with illnesses in which pain is characteristically a prominent presenting symptom. While research into the cause of altered pain perception in psychotic patients is continuing, clinicians should maintain a high index of suspicion of serious medical illness when evaluating such patients. PMID- 2210352 TI - Refusing to terminate a life-threatening pregnancy. AB - A 17-year-old single, Hispanic woman with congenital class III heart disease was found to be 15 weeks pregnant at a clinic visit where she presented in mild failure. She discussed her wish to continue with the pregnancy, knowing it might very well kill her, and plans for her infertile sister to raise the child should she die. The patient's initial refusal and subsequent agreement with the doctor's and family's wish that she terminate the pregnancy is reviewed in the context of adolescent pregnancy and the personal meaning to the patient of the pregnancy and the consultant's intervention. The case was discussed at a consultation-liaison case conference. PMID- 2210353 TI - Drug-induced pneumonitis associated with haloperidol. A case report. PMID- 2210351 TI - Ability to avoid premature treatment. A skill of consultation-liaison psychiatrists. AB - The pressure to diagnose and treat patients rapidly is an enormous stressor for consultation-liaison psychiatrists. The intent of this article is to identify the external and intrapsychic factors that may contribute to such stressors and thus lead to premature interventions. Case vignettes are provided to illustrate those factors, and recommendations are offered to help the consultant recognize the need to acquire an important skill: the ability to avoid premature treatment. PMID- 2210355 TI - Immunotherapy--definition and mechanism. PMID- 2210358 TI - Idiopathic anaphylaxis. PMID- 2210354 TI - Northwestern University allergy-immunology syllabus for medical and pediatric residents and students. PMID- 2210359 TI - Angioedema. PMID- 2210360 TI - Potentially fatal asthma. PMID- 2210356 TI - Allergic bronchopulmonary aspergillosis. PMID- 2210357 TI - Allergic rhinitis. PMID- 2210362 TI - Atopic dermatitis. PMID- 2210361 TI - Status asthmaticus. PMID- 2210364 TI - Food allergy. PMID- 2210363 TI - The detection of IgE antibody. PMID- 2210365 TI - Hypersensitivity pneumonitis. PMID- 2210367 TI - Sinusitis. PMID- 2210369 TI - Urticaria. PMID- 2210368 TI - Unproven techniques. PMID- 2210370 TI - Through the centuries with food and drink, for better or worse. VII. PMID- 2210366 TI - Occupational immunologic lung disease. PMID- 2210371 TI - Buckwheat-poisoning with report of a case in man (1909) PMID- 2210372 TI - Developmental and thyroid hormone-dependent regulation of pancreatic genes in Xenopus laevis. AB - We have isolated and sequenced a cDNA encoding Xenopus laevis pancreatic trypsin, which has approximately 70% amino acid sequence identity to mammalian trypsinogen. Northern blotting analysis shows that the trypsin gene is activated just before the tadpole starts to feed, reaches peak activity in the swimming tadpole (premetamorphosis), and is then repressed during prometamorphosis, attaining its lowest activity at the climax of metamorphosis. The same gene is then activated again in frogs but to a much lower level. The pattern of the changes in trypsin gene expression is followed by at least two other pancreas specific genes and marks the remodeling of the pancreas of the animal at metamorphosis. Thyroid hormone, which is the causative agent of metamorphosis, can down-regulate trypsin gene expression prematurely. PMID- 2210374 TI - A Sequential splicing mechanism promotes selection of an optimal exon by repositioning a downstream 5' splice site in preprotachykinin pre-mRNA. AB - To explore the structural basis of alternative splicing, we have analyzed the splicing of pre-mRNAs containing an optional exon, E4, from the preprotachykinin gene. This gene encodes substance P and related tachykinin peptides by alternative splicing of a common pre-mRNA. We have shown that alternative splicing of preprotachykinin pre-mRNA occurs by preferential skipping of optional E4. The competing mechanism that incorporates E4 into the final spliced RNA is constrained by an initial block to splicing of the immediate upstream intervening sequence (IVS), IVS3. This block is relieved by sequential splicing, in which the immediate downstream IVS4 is removed first. The structural change resulting from the first splicing event is directly responsible for activation of IVS3 splicing. This structural rearrangement replaces IVS4 sequences with E5 and its adjacent IVS5 sequences. To determine how this structural change promoted IVS3 splicing, we asked what structural change(s) would restore activity of IVS3 splicing defective mutants. The most significant effect was observed by a 2-nucleotide substitution that converted the 5' splice site of E4 to an exact consensus match, GUAAGU. Exon 5 sequences alone were found not to promote splicing when present in one or multiple copies. However, when a 15-nucleotide segment of IVS5 containing GUAAGU was inserted into a splicing-defective mutant just downstream of the hybrid exon segment E4E5, splicing activity was recovered. Curiously, the 72 nucleotide L2 exon of adenovirus, without its associated 5' splice site, activates splicing when juxtaposed to E4. Models for the activation of splicing by an RNA structural change are discussed. PMID- 2210373 TI - Cloning of the Schizosaccharomyces pombe TFIID gene reveals a strong conservation of functional domains present in Saccharomyces cerevisiae TFIID. AB - The gene encoding the Schizosaccharomyces pombe TATA box-binding factor (TFIID) was cloned and sequenced. The gene contains three introns and codes for a polypeptide of 231 amino acids. The cDNA-expressed protein showed both TATA box binding and basal transcription activities. The carboxy-terminal three-quarters of S. pombe TFIID shares an extraordinary degree of amino acid sequence homology with a corresponding region of Saccharomyces cerevisiae TFIID that has been shown to be necessary and sufficient for TATA box-binding and basal transcription activities. In contrast, the amino-terminal regions of the S. pombe and S. cerevisiae TFIIDs differ markedly in amino acid sequence and composition. Structure and function relationships of TFIID are discussed in light of these data. PMID- 2210375 TI - Adenovirus terminal protein mediates both nuclear matrix association and efficient transcription of adenovirus DNA. AB - Adenovirus DNA is tightly bound to the nuclear matrix throughout the course of infection. Analysis of adenovirus DNA from infected HeLa cell nuclei after extraction with lithium diiodosalicylate and digestion with restriction enzymes demonstrated that the sites of tightest attachment occur in the terminal fragments of the linear viral chromosome. Analysis of viruses mutated in the precursor terminal protein coding sequence demonstrated that the terminal protein, which is covalently attached to the 5' end of each DNA strand, mediates the tight binding. Virions containing chromosomes with mutant terminal proteins were unpackaged and viral DNA accumulated in the nucleus at a normal rate and competed for the limiting component during transcription complex formation, but their early genes were transcribed at reduced efficiency by both RNA polymerases II and III. The transcriptional defects were not complemented by coinfection with a wild-type virus. We propose that the adenovirus chromosome may exist as a single chromatin domain during infection and that binding of DNA to the nuclear matrix may play a critical role in adenovirus transcription. PMID- 2210376 TI - An RNA polymerase I termination site can stimulate the adjacent ribosomal gene promoter by two distinct mechanisms in Xenopus laevis. AB - On the ribosomal genes of Xenopus laevis, the T3 terminator is located approximately 60 bp upstream of the 5' boundary of the gene promoter. We have shown previously that mutation of the terminator simultaneously abolishes termination and impairs initiation by RNA polymerase I. Here, we show that the terminator influences the promoter by two distinct mechanisms. In one mechanism the terminator protects the promoter by preventing polymerase from reading through the initiation complex. In a second mechanism, the terminator interacts directly with the promoter, whether or not termination occurs. This positive interaction requires precise positioning of the terminator relative to the promoter and is sensitive to movement of the terminator by as little as 1 or 2 bp. We conclude that the terminator and promoter interact as one interdependent complex. PMID- 2210378 TI - Design and cloning of a synthetic gene for the flounder antifreeze protein and its expression in plant cells. AB - A synthetic gene coding for the winter flounder antifreeze protein (AFP) has been constructed. A new strategy for the synthesis has been employed such that one strand of the duplex was chemically synthesized and the other was produced enzymatically by chain extension. The chemically synthesized blocks were constructed so that the second strand was self-priming. The resulting DNA fragment was incorporated into the vector, pGCS1, which contained a translational fusion of the sequence encoding AFP and the N terminus of cat (encoding chloramphenicol acetyltransferase, CAT), under the control of the cauliflower mosaic virus 35S promoter. This plasmid was introduced into protoplasts of corn (var. Black Mexican Sweet) by electroporation. Production of the fusion peptide was monitored by CAT assay and Western blotting with antisera to AFP and CAT. PMID- 2210377 TI - Induction by HMBA and DMSO of genes introduced into mouse erythroleukemia and other cell lines by transient transfection. AB - We have found rapid induction of various genes, including human globin genes, in response to hexamethylene bisacetamide (HMBA) and dimethyl sulfoxide (DMSO) in transiently transfected cells. In mouse erythroleukemia cells (MELCs), this effect is detected within 1 hr of exposure of the cells to inducer before the endogenous mouse globin genes are induced. It does not require protein synthesis and is reversed if the inducer is removed. This and other evidence suggest that the mechanism involves a change in activity of a factor intimately involved with transcription, probably as a result of post-translational modification. As such, it may represent an early triggering event in terminal differentiation, and its relevance to the expression of human globin genes in stable transfectants and to induction of the mouse globin genes is discussed. Other cell lines (K562 and NSO) also show this response, which may therefore involve a ubiquitous mechanism. We also found that HMBA depresses the expression of endogenous globin genes in K562, the opposite of this differentiation inducer's effect on MELC. PMID- 2210380 TI - Cloning and sequence determination of cDNA encoding a second rat liver peroxisomal 3-ketoacyl-CoA thiolase. AB - 3-Ketoacyl-coenzyme A thiolase (thiolase) catalyzes the final step of the fatty acid beta-oxidation pathway in peroxisomes. Thiolase is unique among rat liver peroxisomal enzymes in that it is synthesized as a precursor possessing a 26 amino acid (aa) N-terminal extension which is cleaved to generate the mature enzyme. To facilitate further examination of the synthesis, intracellular transport and processing of this enzyme, cDNA clones were selected from a lambda gt11 rat liver library using antiserum raised against peroxisomal thiolase. Upon sequencing several cDNA clones, it was revealed that there are at least two distinct thiolase enzymes localized to rat liver peroxisomes, one identical to the previously published rat liver peroxisomal thiolase (thiolase 1) [Hijikata et al., J. Biol. Chem. 262 (1987) 8151-8158] and a novel thiolase (thiolase 2). The THL2 cDNA possesses a single open reading frame of 1302 nucleotides (nt) encoding a protein of 434 aa (Mr 44790). The coding region of THL2 cDNA exhibits 94.6% nt sequence identity with THL1 and 95.4% identity at the level of aa sequence. Northern-blot analysis indicates that the mRNA encoding thiolase 2 is approx. 1.7 kb in size. The mRNA encoding thiolase 2 is induced approx. twofold upon treatment of rats with the peroxisome-proliferating drug, clofibrate. In contrast, the thiolase 1 mRNA is induced more than tenfold under similar conditions. PMID- 2210379 TI - The methylation-free status of a housekeeping transgene is lost at high copy number. AB - Transgenic mouse lines were established bearing tandem arrays of a fusion construct comprising the promoter region of a housekeeping gene, HMGCR, encoding 3-hydroxy 3-methylglutaryl CoA reductase, linked to a bacterial cat reporter gene encoding chloramphenicol acetyltransferase (CAT). CAT activity was observed in all transgenic mouse tissues examined. The methylation state of the fusion transgene was determined. In non-transgenic mice the endogenous HMGCR promoter is devoid of methylation while flanking regions are extensively modified. In HMGCR cat transgenic mice the fusion gene promoter was found to be similarly hypomethylated. However, the extent of hypomethylation varied with copy number: methylation-free status was progressively lost with increasing transgene copy number. Further transgenic mouse lines were constructed carrying a truncated HMGCR regulatory region linked to cat. Transgene expression and hypomethylation were observed in testis but not in any other tissue, and testis-specific methylation-free status was also lost at high copy number. Loss of hypomethylation at high copy number may indicate that saturable DNA-binding factors normally protect the HMGCR promoter from methylation. PMID- 2210383 TI - A hormone response element upstream from the human alcohol dehydrogenase gene ADH2 consists of three tandem glucocorticoid receptor binding sites. AB - The 5'-flanking region of the human gene encoding beta-alcohol dehydrogenase (ADH2) was shown by DNase I footprinting to contain three tandem binding sites for purified glucocorticoid receptor. The three binding sites lie very close together between nucleotide (nt) positions -245 and -171 with respect to the transcription start point. DNase I footprinting using a rat liver nuclear extract indicated a lack of protection of the glucocorticoid receptor binding sites, but protection of a sequence between nt -209 and -191 which partially overlaps the glucocorticoid receptor binding sites I and II. This site has homology with the known binding site for hepatocyte nuclear factor 1 (HNF1). ADH2 promoter DNA fragments containing various lengths of 5'-flanking sequences were fused upstream from the gene encoding chloramphenicol acetyltransferase (cat) and transfected into the HepG2 human hepatoma cell line. The resulting cat expression was subject to induction by dexamethasone in constructions containing ADH2 DNA between nt 272 and -171. This indicates that the glucocorticoid receptor binding sites identified by footprint analysis function as a glucocorticoid response element (GRE) in a liver cell line. Heterologous ADH-cat fusions, in which the ADH2-GRE was fused to the adenovirus major late promoter, exhibited glucocorticoid induction of cat expression in CV-1B cells when cotransfected with a glucocorticoid receptor expression vector. Glucocorticoid regulation in CV-1B was observed when either all three glucocorticoid receptor binding sites (sites 0, I, II) or the two distal sites (sites 0, I) were present. Overall, these results indicate that the ADH2 gene possesses a functional GRE which can potentially regulate expression transcriptionally.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210381 TI - Analysis of the human, bovine and rat 33-kDa proteins and cDNA in retina and pineal gland. AB - A monoclonal antibody (mAb) was produced against a bovine retinal 33-kDa protein. Several clones of 33-kDa protein were isolated from each library of cDNA from human, bovine and rat retinas and rat pineal gland by mAb screening and by hybridization with cDNA probes. Each of the four cDNA sequences was determined and amino acid (aa) sequences were deduced from the nucleotide sequences. The latter were nearly identical in rat retina and rat pineal gland (99.6%) and were similar in human, bovine and rat retina (more than 87%). Each of these cDNAs had one long ORF and encoded 245 or 246 aa. The deduced aa sequences in rat retina and rat pineal gland were virtually identical and the sequences in human, bovine and rat retina were highly homologous (more than 88%). The predicted Mr for each of these proteins was 28,246 in the human, 28,176 in bovine, 28,143 in rat retina, and 28,129 in rat pineal gland. Each of the sequences has a putative site for phosphorylation by A kinase; we have confirmed that the putative site is Ser73. These results show that the 33-kDa proteins in the retina and pineal gland have the same sequences and the same phosphorylation site and suggest that the functional role of this protein is the same in the retina and pineal gland. PMID- 2210382 TI - Use of the human elongation factor 1 alpha promoter as a versatile and efficient expression system. AB - We have characterized the promoter region of the human elongation factor 1 alpha encoding gene (EF-1 alpha) and developed a versatile expression system which has a wide host range and a high efficiency of gene expression. To identify the promoter region of the EF-1 alpha gene necessary for efficient gene expression, we constructed four pEF-CAT plasmids that have the bacterial cat gene fused to four different sites of the human EF-1 alpha gene: (i) ligated to the end of the TATA box (pEF220-CAT); (ii) ligated in exon 1 (pEF204-CAT and pEF233-CAT), and (iii) ligated in exon 2 (pEF321-CAT). All the pEF-CAT plasmids were highly expressed in all the cell types tested, including fibroblasts and lymphoid cells. Plasmid pEF321-CAT, which contains the first exon and the first intron, gave the highest level of cat expression. Plasmids pEF204- and pEF233-CAT, which contain part of the first exon but do not contain the first intron, were less efficient in cat expression than was pEF321-CAT. Plasmid pEF220-CAT, which lacks both the first exon and the first intron, was the least efficient. Plasmid pEF321-CAT was several- to 100-fold more efficient in cat expression than plasmid pSV2-CAT depending on the recipient cell types. The promoter of pEF321 plasmid also directed the stable expression of the bacterial neo gene more efficiently than the promoter of the simian virus 40 (SV40) early gene or the long terminal repeat of Rous sarcoma virus. Using this system, the SV40 early gene and the cDNA encoding human CD4 were also expressed efficiently. PMID- 2210384 TI - Structure of the human genomic region homologous to the bovine prochymosin encoding gene. AB - Two human genomic libraries were probed with bovine prochymosin (bPC) cDNA. Recombinant clones covering a genomic region homologous to the entire coding region and flanking sequences of the bPC gene were isolated. Human sequences homologous to exons of the bPC gene are distributed in a DNA fragment of 10 kb. Alignment of the human sequences and the exons of bPC reveals that the human 'exons' 1-3, 5 and 7-9 have sizes identical to the corresponding bovine exons, but a nucleotide (nt) has been deleted in the human exon 4 and two nt in the human exon 6. The aligned human sequence and the coding part of bPC gene share 82% nt homology, the value ranging, in separate exons, from 76 (exon 1) to 84% (exons 5 and 6). 150 bp of 5'-flanking sequence of the human gene has 75% homology to the corresponding region of bPC gene and contains a TATA-box in a similar position. A 1-nt deletion in the human exon 4 would shift the translational reading frame of a putative human PC mRNA relative to bPC mRNA, and result in an in-phase terminator spanning codons 163 and 164 in bPC mRNA. Another terminator in-phase with the amino-acid sequence encoded by the bPC gene occurs in the human exon 5 and the second frameshift mutation in exon 6. Thus, the nt sequence analysis of the human genomic region has revealed the presence of mutations that have rendered it unable to produce a full-length protein homologous to bPC and, therefore, we refer to this gene as a human prochymosin pseudogene (hPC psi). Blot-hybridization analysis of human genomic DNA indicates that hPC psi is a single gene in the human genome. PMID- 2210388 TI - A cDNA encoding human ribosomal protein S24. AB - We describe the isolation and nucleotide sequence of a cDNA encoding the human 40S ribosomal subunit protein (r-protein) S24 (Mr 15,425). Human S24 is virtually identical to the r-protein encoded by a cloned Xenopus laevis cDNA previously identified as S19 [Amaldi et al., Gene 17 (1982) 311-316]. PMID- 2210385 TI - Antisense RNA of the latent period gene (MER5) inhibits the differentiation of murine erythroleukemia cells. AB - The MER5 cDNA was cloned from RNA preferentially synthesized in murine erythroleukemia (MEL) cells during the early period of MEL cell differentiation. To understand the role of the MER5 gene in the differentiation, we have transferred the MER5 cDNA into MEL cells in both sense and antisense orientations under control of the promoter of the human metallothionein gene. Only in the transformants with the antisense MER5 cDNA, did their elevated expression inhibit differentiation. The result suggests that the MER5 gene product may promote early events in the differentiation of MEL cells. PMID- 2210387 TI - Primary structure of bovine lactate dehydrogenase-A isozyme and its synthesis in Escherichia coli. AB - Eleven cDNA clones encoding lactate dehydrogenase(LDH)-A isozyme were isolated from a bovine lymphocyte cDNA library, and the nucleotide sequences of three of the clones (pLDH5, pLDH9 and pLDH12) were determined. With the exception of variation in the 5' portion, two cDNA clones (pLDH9 and pLDH12) appeared to contain the full-length cDNA of 1786 bp, consisting of the protein-coding sequence (996 bp), the 5'- and the 3'-untranslated regions and the poly(dA) tail. The predicted amino acid (aa) sequence of bovine LDH-A (332 aa) showed 96.7% homology with that of pig LDH-A. The protein-coding cDNA region (1650 bp) was inserted into an Escherichia coli expression vector ptac11 and expressed. The protein synthesized in E. coli showed enzyme activity of LDH and was identified by cellogel electrophoresis as LDH-5 isozyme whose subunit M chain is the product of the LDH-A gene. PMID- 2210386 TI - The effect of phage T7 lysozyme on the production of biologically active porcine somatotropin in Escherichia coli from a gene transcribed by T7 RNA polymerase. AB - We have analyzed the inducible synthesis of recombinant porcine somatotropin (rPST) from the phage T7 gene 10 promotor on the vector pET3a [Rosenberg et al., Gene 56 (1987) 125-135]. Low-level synthesis of phage T7 lysozyme is crucial for high-level synthesis (40%) of rPST, which is greatly reduced if T7 lysozyme synthesis is absent or too high. The synthesis of rPST mRNA is optimized in those constructs coding for low levels of T7 lysozyme, with a reduction in mRNA levels in constructs coding for higher levels of T7 lysozyme or no lysozyme. The rPST can be readily purified following a single chromatographic step and is biologically active as determined by the tibia test following administration to hypophysectomized rats. PMID- 2210389 TI - Geriatric nutrition: advice from an expert panel. PMID- 2210391 TI - Practical nutritional advice for the elderly, Part I: Evaluation, supplements, RDAs. A geriatrics panel discussion. AB - By the time someone reaches old age, he or she thinks they know everything they want, or need, to know about nutrition. Yet malnutrition and its many effects are a rising danger. In this first of two installments of a panel discussion, nutritional experts review practical concerns for the treating physician, including assessment, interpretation of weight loss, use of supplements, and the relevance of RDAs to the elderly. PMID- 2210390 TI - Human growth hormone: the Fountain of Youth? PMID- 2210394 TI - Pneumonia syndromes: a clinical approach in the elderly. AB - Important in the pathogenesis of pneumonia in the elderly patient are chronic diseases, including diabetes mellitus, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, and cerebrovascular disease. Also vital are the changes that take place in the immune system and mucociliary clearance mechanisms of the lung. The clinician should be aware of these risk factors, especially since the mortality rate of lower respiratory infections approaches 40% in these elderly patients. Treatment guidelines are included. PMID- 2210392 TI - Dementia, depression, or grief? The differential diagnosis. AB - Depression, grief, and dementia are conditions frequently encountered among the community-living elderly. This review offers a primary care perspective of the distinguishing features for each and discusses the special issues of managing the elderly. Major depression in the elderly usually responds to antidepressant medication, whether the depression occurs alone (endogenous) or as a response to another condition (reactive). PMID- 2210393 TI - Assessing competency in the elderly. AB - The doctrine of informed consent requires that a patient understand the medical procedure being proposed, that consent be voluntary, and that the patient be competent to give consent. Because of declining cognitive functioning, elderly patients are at significant risk of becoming incompetent and, therefore, unable in the eyes of the law to give informed consent. Advance directives allow competent patients to tell their doctors and the world in general what their health care choices are should they not be able to make their choices clear in the future. The living will and durable power of attorney are two types of advance directives that are legally binding in most states. PMID- 2210395 TI - Aging and the skin: recognizing and managing common disorders. AB - Senescent changes in structure and function of the skin and chronic solar radiation damage predispose the skin of the elderly to certain inflammatory and infectious diseases. In this context, the diagnosis and treatment of senile xerosis and pruritus are discussed, as are the common types of dermatitides, infections, and infestations. PMID- 2210397 TI - Is the special competency exam fair to primary care? PMID- 2210399 TI - [Nicotinic acid in dust-gas emissions from the biochemical industrial plants producing yeast for animal feed]. AB - The presence of nicotine acid in the dustgaseous pollution from biochemical plants producing fodder yeast has been shown. Its allergic and sensitizing role compared to the same properties of protein-containing dust has been pointed out. It has been suggested that MAC of nicotine acid should be established for the sanitary-protective zone of microbiological industry enterprises. PMID- 2210396 TI - Semantic deterioration in Alzheimer's: the patterns to expect. AB - Differentiating language changes between the normal aged and those in the early stages of dementia is never simple. Knowing the differences and what to expect can aid in making this diagnosis. PMID- 2210398 TI - [Experimental substantiation of MPEL of dibenz(a,n)anthracene in atmospheric air]. AB - Overt dependence of lung tumour development on the values of the dose administered was shown in experiments on inbred white rats under intratracheal administration of various doses of dibenz (a, h) anthracene (DBA); minimal-effect dose and maximal no-effect dose of DBA were established in the experiment. A theoretically calculated allowable dose was used to calculate MAC of the chemical under study for the ambient air 5 ng/m3 was recommended as an average 24-hour maximum allowable concentration of DBA in ambient air. PMID- 2210400 TI - [Hygienic substantiation of a sanitary protective area for the functioning and recultivated rock open-cut coal mines]. PMID- 2210402 TI - [Motor activities of 1st grade children from general-education rural schools]. AB - The optimal level of motor activity of 6-year old pupils providing for the improvement of the health status, a steady level of working ability and functional status of child organism has been established through a wide purposeful use of various forms and means of physical education. The possibility to extrapolate motor functions has been confirmed, and it is for the first time that rapid development of finely coordinated movements of hand muscles has been achieved under the influence of game training equipment and special exercises. PMID- 2210405 TI - [The system of database management for detection of the causes of mass morbidity]. PMID- 2210403 TI - [Hygienic evaluation of the capacity of preschool institutions in relation to planning and equipment of group facilities]. AB - The area of the group premises in child preschool centers (50 m2) with the existing number of children in a group (25) does not provide hygienic conditions for the organization of regime requirements. Physiological studies of the functional status of children, ergonomic calculations and pedagogical observations made it possible to recommend that the number of preschool groups should be decreased down to 20 children. PMID- 2210406 TI - [Socio-hygienic studies of life style and health status of medical students]. PMID- 2210401 TI - [Accumulation of metals in animal body after their administration with drinking water]. AB - It has been stated that separate and simultaneous administration into the animal organism of low doses of copper, lead and nickel with drinking water is accompanied by dose-dependent change in the level of not only administered but also endogenic elements in animals' organs. A supposition has been made that the character of changes in the content of the administered and endogenic metals is associated in the organism of animals with the depth of disturbances in metabolic processes. PMID- 2210404 TI - [Changes in lymphocyte size after chronic exposure to radiation and chemical factors]. AB - Results of the analysis of changes in peripheral blood lymphocytes size under chronic exposure to external gamma radiation and pesticide chlorophos++ in combination and separately are presented. It has been found out that under exposure of animals to radiation or the pesticide it is small and big lymphocytes respectively which most significantly suffer quantitatively. Under the joint radiation ++-chemical exposure of the organism the number of both types of cells is reduced simultaneously. PMID- 2210407 TI - [A method of certification of students of public health departments of medical schools]. PMID- 2210408 TI - [Analysis of genotoxic effects in professional groups]. PMID- 2210409 TI - [Hygienic studies of materials used for children's toys]. PMID- 2210413 TI - [Hygienic concept of healthy life style]. PMID- 2210410 TI - [Evaluation of combined effects of multicomponent mixtures of chemical substances by the leading factor]. PMID- 2210411 TI - [Characteristics of metabolism of erythrocytes exposed to chemical substances]. PMID- 2210412 TI - [Epidemiology of smoking among medical students]. PMID- 2210414 TI - [Gas-chromatographic method of determining the levels of phenol in reservoir water]. PMID- 2210415 TI - [Analysis of epichlorohydrin in the model system simulating beverages]. PMID- 2210416 TI - [Gas-chromatographic analysis of propylene oxide in the air and biological media]. PMID- 2210419 TI - [Improving the organization of state sanitary control of ships]. PMID- 2210420 TI - [Reorganization of the activities of sanitary and epidemiological services in experimental elaboration of new forms of management, planning and financing of public health]. PMID- 2210417 TI - [The theory of hygienic standardization]. PMID- 2210418 TI - [The nature of cumulative effect of benzo(a)pyrene]. PMID- 2210421 TI - [Current problems of occupational pathology]. PMID- 2210422 TI - [Clinico-functional and morphological characteristics of the stomach in patients with vibration disease]. AB - The contributors provide research data on the clinical manifestations, secretory and pepsinogenous function, morphological and histologic structures of stomach diseases caused by local vibration induced vibration disease. A correlation was established depending on the duration of work. As a result of clinico-functional and morphologic techniques used, no full correlation was traced between the stomach structure and function in VD patients, which seem to be of practical value for medical examination of workers engaged in unfavorable working conditions. PMID- 2210423 TI - [Endoscopic and morphological characteristics of the bronchi and lungs in asbestosis and dust-induced bronchitis in asbestos-textile industry workers]. AB - A bronchofibroscopy study of cases with histologic investigation of the bronchi and pulmonary mucous biopsy of 29 asbestos-textile workers, revealed diffuse bilateral endo-bronchitis (DBE) with concomitant tracheitis at different stages. No correlation was found between the endoscopy pictures and the clinical manifestations of asbestosis and dust bronchitis. The asbestosis diseased patients displayed pulmonary fibrosis++ without granulomatous inflammation in the asbestos dusts zone. In some cases, bronchial epithelium diffuse metaplasia was diagnosed with some dysplasia elements, as well as papillomatosis and malignant tumours in the lungs. Dust bronchitis++ and asbestosis can perform precancerous conditions in the lungs, what should be taken into account in cancer prevention measures for asbestos industry workers. PMID- 2210424 TI - [Correlations of the processes of metabolism of metals after their separate administration and their hygienic significance]. AB - The article exhibits the results of experimental studies in rats of vanadium and silver metabolism after isolated intratracheal introduction of the metals. Radioisotopic indication was used to investigate the processes of the metals' absorption in the blood, their distribution to the secondary depositories and elimination from the organism. A close correlation between specific stages of metabolism was identified, and the leading role of absorption in the toxicokinetics of the metals was established. It was proved that vanadium intensive absorption and transport were followed by its rapid elimination from the organs. Retention of silver at the introduction site--in the lungs was followed by its slower elimination. The data obtained is applicable in determining the site of toxicity effect. PMID- 2210425 TI - [Immunologic reactivity of the body in pregnant greenhouse workers]. AB - The proposed research data proved that female green-house workers were exposed to hazardous occupational factors, which resulted in neuroendocrine disorders, manifesting themselves at early pregnancy, at the stage of gestational dominant formation. Elimination of the contact with the hazardous labour conditions, with concomitant pathogenetic treatment, contributed to the restoration of the normal immune status. PMID- 2210426 TI - [Substantiation of group MPEL for dispersive anthraquinone dyes]. AB - The article presents results of the toxicological studies of 65 replaced anthraquinones: amino-, diamino-, haloido-, hydro- and oxianthraquinones. A similar polytropic toxic action was identified. MACs for anthraquinones, alpha aminoanthraquinones and K-type dispersal dye-stuff were established at 5 mg/m3. The toxicity properties of 11 other dispersal dye-stuffs with anthraquinone and NF disperser were studied. Similarity in the toxic properties of the dispersal dye-stuffs and those of the earlier standardized anthraquinone derivatives were established. The group MACs for the pigment and NF disperser containing dispersal anthraquinone dye-stuffs at 5 mg/m3 was established and subsequently formally adopted. A possibility of chemical assessment of dye-stuff dust concentrations against NF disperser (MAC at 2 mg/m3) was taken into account. PMID- 2210427 TI - [Analysis of methodological approach to the evaluation of toxicity of complex mixtures of relatively constant composition used in industry (review of the literature)]. AB - Basing on literature data and the author's personal experience, the article displays current approaches to the toxicological assessment of industrial complex mixtures with permanent compositions. These include two main approaches to the detection of major components: a) the establishment of the individual substances ratio in the toxicological parameters, and b) the application of the regression coefficients and their derivatives. Toxicity assessment against the toxicological parameters of individual substances is also substantiated. PMID- 2210428 TI - [Current postgraduate training in occupational medicine]. PMID- 2210429 TI - [Determining benzyl alcohol and benzaldehyde levels in the air during azeotropic dyeing of textiles]. PMID- 2210430 TI - [A method of determining the permissible time of working with vibration generating hand-operated machines]. AB - To limit the hazardous action of local vibration, a special nomogram was elaborated to determine, basing on newly established hygienic norms and regulations, the admissible duration of working with hand-operated vibrators. The normogram was based on the relation of vibrocontact duration to the vibration intensity, and was recommended to be applied to hand-operated vibrators with vibration intensity lower 10 cm/s (126dB). PMID- 2210431 TI - [Proteinuria as an indicator of occupational stress in helicopter pilots]. PMID- 2210432 TI - [The main parameters of winking]. PMID- 2210433 TI - [Study of zinc and cadmium chloride toxicity using human embryo fibroblast cultures]. PMID- 2210434 TI - [Psychoemotional status in vibration disease]. AB - 193 patients affected with vibration disease caused by local vibration and 111 healthy people were examined to evaluate their psychoemotional state. A comparative analysis of the data obtained proved high prevalence of pathologic emotional disorders, while somatic manifestations of anxiety against social introversion were mostly predominant among them. A dynamic investigation confirmed both the objectiveness of the disorders in question and expedience of specific approaches to their therapy. PMID- 2210435 TI - [Hygienic standardization of neodymium fluoride in the air of the work area]. PMID- 2210436 TI - [Radiation safety in using current x-ray analytical devices]. PMID- 2210437 TI - [Effect of sodium succinate on the development of experimental silicosis]. PMID- 2210438 TI - [Results of psychometric and questionnaire methods in the evaluation of noise and vibration on floating oil rigs in the Caspian sea]. AB - A psychometric study of noise and vibration was performed at different parts of the Caspian floating oil rigs. The analysis of 500 questionnaires received from the personnel showed that the correlation coefficients for different values, depending on the parameters of the levels, were 0.71-0.87 for noise and 0.33-0.44 for vibration. The noise levels calculated for oil workers of different professions, were: in cabins, recreation rooms and working sites 40-52, 57-63 and 73-74 dBA respectively, and the comparative vibration rate levels were 67-74, 79 85 and 90-97 dB, respectively. 273 questionnaires revealed that the acoustic conditions in the abins affected both the process of falling asleep and depth of sleep (correlation coefficients 0.88 and 0.93, respectively). Noise levels at 30 36 dBA did not cause any sleep discomfort. 84% questionnaires contained in average 3.5 complaints, with the maximum 5.2 complaints for the machine operators, and the minimum 3.2 complaints for the electricians who worked in acoustically more favorable conditions. The study proved that the psychometric and questionnaire data in 70% cases corresponded to the results of the laboratory techniques, such as audiometry, chronoreflexometry, tono- and pulsometry, electrocardiometry, etc. The research data received served a basis for noise and vibration hygienic norming in floating oil-rig sites. PMID- 2210439 TI - Genetical, developmental, and thermal regulation of antioxidant enzymes in Neurospora. AB - Three characteristics of the biochemical genetics of antioxidant enzyme regulation in Neurospora and enteric bacteria are analogous. This paper reports two additional analogies:responsiveness to change in respiratory rate or thermal stress. A negative regulatory Neurospora mutant is defective in those responses. Although several differences are noted, the common denominator of the two organisms is probably an oxy-regulon, a global unit of genetic function. The degree of homology of bacterial and fungal antioxidant enzyme regulatory mechanisms at the molecular-genetic and signal transduction levels of organization remains to be examined. The hypothesis that the genetic control of antioxidant enzymes is a prerequisite for cellular differentiation of Neurospora is discussed. PMID- 2210440 TI - Desferrioxamine protects human red blood cells from hemin-induced hemolysis. AB - Hemin binding to red cell membranes, its effect on red cell hemolysis, and it interaction with desferrioxamine (DFO) in these processes were investigated. DFO interacted with hemin via the iron moiety. Blockage of the binding groups in DFO prevented interaction of DFO with hemin, implying the importance of the hydroxamic acid groups in DFO-hemin interactions. Since hemolysis is a result of hemin association with the membrane components, its binding in the presence and absence of DFO was studied. DFO strongly inhibited hemin-induced lysis in a concentration-dependent manner. With 50 microM hemin, 1 mM DFO completely inhibited lysis. Preincubation of ghost membranes with DFO (1 mM) inhibited binding of hemin (50 microM) to membranes by 42%. After ghost membranes were preincubated with hemin (50 microM), the addition of DFO (1 mM) removed 20% of the membrane-bound hemin. It is suggested that DFO may have an important role in alleviating the hemin-induced deleterious effects on the red cell membrane, especially in hemolytic anemias associated with unstable, autoxidized hemoglobins. PMID- 2210441 TI - Detection of lipid peroxidation in lung and in bronchoalveolar lavage cells and fluid. AB - Inhalation of toxic materials such as asbestos, silica, 100% oxygen, ozone, or nitrogen dioxide may lead to an increased production of reactive oxygen metabolites which may initiate lipid peroxidation. Measurement of lipid peroxidation in cells and fluid obtained by bronchoalveolar lavage (BAL), as well as in lung tissue, may aid in monitoring the development and extent of pulmonary damage after inhalation of a toxic substance. In this study, we employed a sensitive assay for detection of malondialdehyde (MDA), a breakdown product of lipid peroxidation. By separation of the adduct with thiobarbituric acid, using a reverse phase high pressure liquid chromatographic technique, we accurately and sensitively measured the content of MDA in BAL cells, lavage fluid, and lavaged lung tissue homogenates of rats. The amounts of sample required for detection of MDA were small enough possibly to be applied to use with human specimens; in addition, recovery of added MDA was acceptable with all types of samples. Inclusion of a metal chelator in the preparation of samples appeared necessary to prevent metal-catalyzed propagation of lipid peroxidation during the assay. Overall, the method described here using samples from rats may be applicable to detecting lipid peroxidation in BAL samples from humans. PMID- 2210442 TI - Oxidative stress induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent toxins and tumor promoters known to man. It is prototypical of many halogenated polycyclic hydrocarbons that occur as environmental contaminants. Pathologic lesions produced by these compounds are mediated by an intracellular receptor protein called the TCDD (Ah) receptor which functions as a trans-acting effector of gene expression. However, the ultimate posttranslational pathways and mechanisms involved in the expression of the toxic manifestations of TCDD have received little attention and remain unclear, yet constitute an important segment in our understanding of the overall mechanism of action of TCDD. Recent studies have demonstrated that an oxidative stress occurs in various tissues of TCDD-treated animals. Evidence indicating production of an oxidative stress by TCDD in rodents is reviewed and includes:enhanced in vitro and in vivo hepatic and extrahepatic lipid peroxidation; increased hepatic and macrophage DNA damage; increased urinary excretion of malondialdehyde; decreased hepatic membrane fluidity; increased production of superoxide anion by peritoneal macrophage; and decreased glutathione, nonprotein sulfhydryl, and NADPH contents in liver. The potential role of reactive oxygen species in tumor promotion by TCDD is discussed. Possible sources and mechanisms of production of reactive oxygen species in response to TCDD are considered in light of current information. Evidence demonstrating the involvement of iron in TCDD-induced formation of reactive oxygen species and DNA damage is reviewed. Oxidative damage may contribute to many of the toxic responses produced by TCDD and its bioisosteres, and may be common to most of the tissue-damaging effects. PMID- 2210443 TI - Human migrating myoelectric complex in relation to gastrointestinal transit of a meal. AB - Feeding interrupts the migrating myoelectric complex in most mammals. This study aimed to assess whether resumption of the migrating myoelectric complex in the human duodenum after eating was related to the gastrointestinal transit of the meal. Five healthy subjects participated in the study. After eating a radiolabelled test meal consisting of mixed liquid and solids, duodenal myoelectric activity and gastrointestinal transit of the meal were determined simultaneously. In spite of considerable variation in entire gastric emptying time between subjects (range 2.5-5.0 hours), significant correlation was found between the completion of gastric emptying and the resumption of duodenal phase III activity within subjects (p less than 0.01). A new technique for recording the duodenal myoelectric activity was used. PMID- 2210444 TI - Acute hypervolaemia increases gastroduodenal resistance to the flow of liquid in the rat. AB - The effect of volume expansion of extracellular fluid on gastroduodenal resistance to the flow of isotonic saline was assessed in three groups of rats using intravenous infusions of isotonic, isotonic-isoncotic, and isotonic isoncotic-isohaemic solutions. The gastroduodenal segment of 29 male Wistar rats was barostatically perfused at a constant pressure gradient of 4 cm H2O and changes in flow (ml/minute) were taken as a reflection of changes in gastroduodenal resistance. Isotonic expansion led to a 33% drop in gastroduodenal flow compared with the normovolaemic period in the same animals (p less than 0.01). Extracellular fluid expansion with isotonic-isoncotic and isotonic isoncotic-isohaemic solutions was associated with reductions in gastroduodenal flow of 29% (p less than 0.05) and 31% (p less than 0.01) respectively. The increase in gastroduodenal resistance is due to hypervolaemia per se and not to haemodilution, decreases in plasma oncotic pressure, or electrolyte imbalance. The effect of hypervolaemia on gastroduodenal resistance, which was reversed by small haemorrhages (0.5-1.0 ml per 100 g body weight), may be due to changes in tonus or phasic motor activity, or both, and may be part of the homeostatic processes that help the organism minimise liquid volume excess. PMID- 2210445 TI - Involvement of M cells in the bacterial invasion of Peyer's patches: a common mechanism shared by Yersinia enterocolitica and other enteroinvasive bacteria. AB - Recent evidence indicates that ileal Peyer's patches represent the main infection route for Yersinia enterocolitica. In this study transmission and scanning electron microscopy have shown that only a small fraction of bacteria present in the lumen adhere to the follicle-associated murine epithelium with no discernible preference for either M or absorptive cells. Yersiniae attached to M cells are phagocytosed and transported from the lumen into the lamina propria. No invasion of columnar absorptive cells was observed. These data, in combination with recently published reports, indicate that the involvement of M cells is a common step in bacterial invasion of Peyer's patches. PMID- 2210446 TI - Circulating antibodies against human colonic extract enriched with a 40 kDa protein in patients with ulcerative colitis. AB - We have previously described a 40 kDa colonic protein(s) which is specifically recognised by tissue-bound immunoglobulin G obtained from the colon of patients with ulcerative colitis. We now report the presence of circulating antibodies against this antigen using an enzyme-linked immunosorbent assay with a highly enriched preparation of the 40 kDa protein from normal colon extracts. Serum was collected from 79 patients with ulcerative colitis, 36 with Crohn's disease, 16 with specific diarrhoeal syndromes, and from 19 normal subjects. Twenty nine of 79 patients with ulcerative colitis, 21 of 36 with Crohn's disease, and all patients with diarrhoea were symptomatic during the collection of sera. The difference in optical density values between patients with symptomatic ulcerative colitis and each of the other groups, including patients with ulcerative colitis in remission, was highly significant (p less than 0.01). Seventy nine per cent of patients with symptomatic ulcerative colitis had optical density values above the means for all other groups. Fifty five per cent of sera from patients with symptomatic ulcerative colitis had optical densities beyond two SDs of the values for all other groups and only two of 71 sera from non-ulcerative colitis patients (one Crohn's disease and one normal subject) had values in this range. These results show the presence of anti-colon antibodies against the 40 kDa protein(s) in the sera of many patients with symptomatic ulcerative colitis. PMID- 2210447 TI - Effect of ulcerative colitis and smoking on rectal blood flow. AB - Rectal blood flow was measured by laser doppler flowmetry over 60 minutes in eight patients with colitis in remission and eight healthy male non-smokers. Ten smokers were also examined on two occasions, one of which included smoking a cigarette. Plasma nicotine concentrations were measured in smokers. All subjects showed a pronounced fall in rectal blood flow in the first 30 minutes and patients with colitis had significantly higher values compared with smokers (p less than 0.002; p less than 0.04) and non-smokers (p less than 0.007; p less than 0.002) during the first and second 30 minutes respectively. Values in smokers and non-smokers were similar, but smoking a cigarette was associated with a significant fall in blood flow (p less than 0.04) and this change was inversely related to the rise in plasma nicotine concentration (r = -0.63; p less than 0.05). The findings may be relevant to the association between colitis and the smoking history. PMID- 2210448 TI - Daytime reduction of gastro-oesophageal reflux after healing of oesophagitis and its value as an indicator of favourable response to maintenance treatment. AB - In order to investigate the response of gastro-oesophageal reflux after medically induced healing of oesophagitis and its relation to the occurrence of relapse during prophylactic treatment, 20 patients with erosive/ulcerative oesophagitis underwent 24 hour oesophageal pH monitoring before and after healing achieved with 12 to 24 week treatment with ranitidine 150 or 300 mg twice daily. Compared with pretreatment values, after macroscopic healing, a significant reduction in daytime median percentage of reflux time (10.0 v 6.5; p less than 0.05) and median number of reflux episodes lasting more than 5 minutes (5-5 v 1.0; p less than 0.05) were observed, whereas during night time reflux frequency and severity did not change. During maintenance treatment with ranitidine 150 or 300 mg nocte, five of the six patients, who had shown no improvement in gastro-oesophageal reflux after acute healing, relapsed. These results suggest that, in contrast with previous work, a decrease in gastro-oesophageal reflux in patients with reflux oesophagitis can be achieved after macroscopic healing, and that the occurrence of such a reduction after acute healing is predictive of a good response to longterm treatment. PMID- 2210449 TI - Soluble interleukin-2 receptor in Crohn's disease: relation of serum concentrations to disease activity. AB - Serum concentrations of soluble interleukin-2 receptor (sIL-2R) were measured as a marker of immune activation in a group of 30 patients with Crohn's disease. sIL 2R concentrations were determined by enzyme linked immunosorbent assay during periods of active and inactive disease and correlated with standard parameters of disease activity. Serum concentrations of sIL-2R were significantly raised in patients with active Crohn's disease compared with patients with inactive disease (p less than 0.001) and control subjects. There was a significant correlation between serum sIL-2R concentrations and disease activity as assessed by the Harvey-Bradshaw index (r = 0.42, p less than 0.01), platelet numbers (r = 0.49, p less than 0.01), and orosomucoid (r = 0.47, p less than 0.01), alpha 1 antitrypsin (r = 0.44, p less than 0.01), and C reactive protein concentrations (r = 0.48, p less than 0.001) but not with the erythrocyte sedimentation rate. Measurement of serum sIL-2R concentration is a simple and useful laboratory means of assessing disease activity. Raised concentrations in patients with active Crohn's disease is further evidence for in vivo immune activation occurring in this disease. PMID- 2210450 TI - Occupational distribution of inflammatory bowel disease among German employees. AB - Previous reports have shown that both Crohn's disease and ulcerative colitis affect people in white collar occupations associated with higher income and higher social class more frequently than other groups in the population. This study sought to carry these analyses one step further and investigate the distribution of inflammatory bowel disease by individual occupations. The German social security statistics for 'rehabilitation' were used to assess the occupational distribution of Crohn's disease and ulcerative colitis. From 1982 to 1988, a total of 12,014 people were granted rehabilitation as a result of inflammatory bowel disease. Low male prevalence of inflammatory bowel disease was found among bricklayers, road construction workers, unskilled workers in brick and stone, unskilled labourers, and security personnel. Low rates were found among women employed in cleaning and maintenance, and in those without occupation. In contrast, a high male prevalence was found among instrument makers, electricians, bakers, and technical assistants. Among female employees, inflammatory bowel disease was significantly associated with sales representatives, office workers, health occupations, and hairdressers. These associations were found in the complete data for 1982-8 as well as in the separate data for the two half periods 1982-5 and 1986-8. Highly significant correlations between the occupational distribution of Crohn's disease and ulcerative colitis were found among both male and female employees. It seems that occupations involving work in the open air and physical exercise are protective, while being exposed to air conditioned artificial working conditions or extended and irregular shift working confer a risk of contracting inflammatory bowel disease. PMID- 2210451 TI - Low diacylglycerol values in colonic adenomas and colorectal cancer. AB - The biochemical events that make colonic epithelial cells proceed along the adenoma-carcinoma sequence are not well understood. The phosphoinositol signal transduction pathway is involved in the regulation of cell growth and differentiation. To determine its role in colonic neoplasias we performed mass measurements of its second messenger sn-1,2-diacylglycerol in biopsy specimens from normal mucosa and neoplasias of the colon. Normal colonic mucosa was also investigated in patients without colonic abnormalities (n = 10). Compared with pooled diacylglycerol values from five colonic sites (100%), values in patients with a normal colon were highest in the ascending colon (120 (5)%, p less than 0.05) and lowest in the rectum (81 (5)%, p less than 0.01). Absolute diacylglycerol values in patients with normal colons (2.62 (0.16) nmol/mg protein) were not significantly different from those found in the normal mucosa of patients with colorectal neoplasias (2.45 (0.17) nmol/mg protein). Both colonic adenomas (n = 15) and colorectal carcinomas (n = 14) showed significantly decreased diacylglycerol values compared with the adjacent normal mucosa of each patient (72 (4)%, p less than 0.001, and 71 (4)%, p less than 0.001 respectively). The appreciable decrease in mass diacylglycerol values clearly distinguishes adenomas and carcinomas of the colon from the surrounding normal mucosa. This finding suggests that profound metabolic changes of the phosphoinositol signal transduction pathway occur early in the adenoma-carcinoma sequence and may be important in colonic carcinogenesis. PMID- 2210452 TI - Relation between rectal sensation and anal function in normal subjects and patients with faecal incontinence. AB - The relation between sensory perception of rapid balloon distension of the rectum and the motor responses of the rectum and external and internal anal sphincters in 27 normal subjects and 16 patients with faecal incontinence who had impaired rectal sensation but normal sphincter pressures was studied. In both patients and normal subjects, the onset and duration of rectal sensation correlated closely with the external anal sphincter electrical activity (r = 0.8, p less than 0.0001) and with rectal contraction (r = 0.51, p less than 0.001), but not with internal sphincter relaxation. All normal subjects perceived a rectal sensation within one second of rapid inflation of a rectal balloon with volumes of 20 ml or less air. Six patients did not perceive any rectal sensation until 60 ml had been introduced, while in the remaining nine patients the sensation was delayed by at least two seconds. Internal sphincter relaxation occurred before the sensation was perceived in three of 27 normal subjects and 11 of 16 patients (p less than 0.001), and could be associated with anal leakage, which stopped as soon as sensation was perceived. The lowest rectal volumes required to induce anal relaxation, to cause sustained relaxation, or to elicit sensations of a desire to defecate or pain were similar in patients and normal subjects. In conclusion, these results show the close association between rectal sensation and external anal sphincter contraction, and show that faecal incontinence may occur as a result of delayed or absent external anal sphincter contraction when the internal anal sphincter is relaxed. PMID- 2210453 TI - Inter- and intraindividual variation in pressure-volume relations of the rectum in normal subjects and patients with the irritable bowel syndrome. AB - The relation between intrarectal volume and pressure during increasing rectal distension by a latex balloon were studied on repeated occasions in 10 healthy adult volunteers to define variations within and between individuals. A wide intersubject variation in the maximum tolerable volume (58-908 ml) and pressure (12.2-108.8 cm H2O) at this end point was seen, and these two values were correlated (r = 0.78). Intrasubject variation in maximum tolerable volume also occurred which was related to study order and progressively reduced with repeated study. In 26 unselected patients with pain predominant irritable bowel syndrome similar intersubject variation was noted and virtually all patients data fell within the calculated 95% confidence limits of the normal individuals. Differentiation between patients and normal subjects was not possible from knowledge of rectal responses. These noticeable inter- and intrasubject variations in rectal responses to distension need to be considered whenever similar techniques are proposed for use in the study of rectal disease or of rectal response to treatment. PMID- 2210454 TI - Referral of patients with primary biliary cirrhosis for liver transplantation. AB - All patients with primary biliary cirrhosis referred to this unit for consideration for transplantation between April 1981 and January 1989 were analysed retrospectively to assess whether disease stage at referral affects the outcome after grafting and whether greater awareness of the benefits of the procedure means that patients are now being referred at an earlier stage. Seventy of the 107 patients have been grafted, with an overall one year actuarial survival of 62%. A better prognosis at the time of referral, as assessed by both serum bilirubin concentration and a mathematically derived prognostic index, was associated with a greater probability of survival after grafting. Patients in the tertile with the best prognosis (median serum bilirubin concentration at referral 84 mumol/l and estimated survival in the absence of transplantation of more than nine months) had a 78% one year actuarial survival after transplantation, whereas those in the tertile with the worst prognosis (median serum bilirubin concentration 467 mumol/l and estimated survival of less than four months) had a one year actuarial survival of only 50%. No trend towards earlier referral of patients, however, was shown using either of these two markers. This retrospective analysis suggests that many patients are being referred too late for an optimal outcome. We recommend that patients with primary biliary cirrhosis who are potential candidates for liver grafting should be referred to a transplant centre before the serum bilirubin concentration approaches 150 mumol/l. PMID- 2210455 TI - Pancreatic duct abnormalities in gall stone disease: an endoscopic retrograde cholangiopancreatographic study. AB - This study was carried out to assess pancreatic duct abnormalities in gall stone disease. Endoscopic retrograde cholangiopancreatograms of 50 patients with gall stone disease were analysed and the results compared with those obtained in 33 patients investigated for cholestatic jaundice who were found to have a normal biliary tree (control group). Abnormal pancreatograms were obtained in 24 (48%) patients with gall stone disease and in only two (6%) in the control group; the differences were statistically significant (chi 2 = 14.3; p less than 0.001). The patients in the control group showed mild abnormalities as did those in the gall stone group. The frequency of various abnormalities were: mild 16 (32%), moderate five (10%), and severe three (6%). Pancreatic duct abnormalities were more severe and occurred more frequently in patients with gall stones who had stones in the biliary tree than in patients with a normal biliary tree (postcholecystectomy patients, 55% v 25%) but the difference between the two groups just failed to be significant (chi 2 = 3.34). In conclusion, nearly half of all patients with gall stone disease have pancreatic duct abnormalities and in 16% these were severe enough to be labelled as chronic pancreatitis. PMID- 2210456 TI - Loss of duodenal folds allows diagnosis of unsuspected coeliac disease. AB - We report three patients with coeliac disease who presented without the classic features of malabsorption and who underwent biopsy and were diagnosed only because of the endoscopic finding of the disappearance of Kerckring's folds in the descending duodenum. This sign constitutes a new and valid aid for the identification of patients with otherwise unsuspected coeliac disease. PMID- 2210457 TI - Adult hepatic fibropolycystic disease presenting as obstructive jaundice. AB - Obstructive jaundice caused by compression of the common hepatic duct by a simple hepatic cyst in a 31 year old Europid man is reported. The jaundice and duct compression resolved after percutaneous aspiration of the cyst under ultrasound direction and the patient has been well for 12 months. PMID- 2210458 TI - Anomalous short plasma elimination half life in a patient intoxicated with bismuth subcitrate. PMID- 2210459 TI - Macrophage activity in inflammatory bowel disease. PMID- 2210460 TI - Inhibition of nocturnal acidity. PMID- 2210461 TI - Are the inflammatory bowel diseases autoimmune disorders? PMID- 2210462 TI - Evaluation of the magnitude of gastro-oesophageal reflux in Barrett's oesophagus. AB - A manometric study to determine the role of gastro-oesophageal reflux in Barrett's oesophagus was performed on 20 patients with Barrett's oesophagus and 53 patients with reflux oesophagitis without Barrett's oesophagus (25 with mild oesophagitis and 28 with severe oesophagitis). For the same reason, the 20 patients with Barrett's oesophagus also underwent 24 hour continuous oesophageal pH monitoring, and the results obtained were compared with those of 20 oesophagitis patients without Barrett's oesophagus (10 with mild oesophagitis and 10 with severe oesophagitis). The manometric results show that the motor changes found in the Barrett's group are specific but similar to the motor dysfunction associated with reflux oesophagitis. Motor anomalies are probably related more to the inflammatory process in the oesophageal wall than to the metaplastic changes themselves. The pH monitoring results show that while reflux in the Barrett's oesophagus patients was greater overall than in the oesophagitis group without Barrett's oesophagus, the changes are similar when the results are compared with the severe oesophagitis group. In conclusion there are other factors besides gastro-oesophageal reflux involved in the pathogenesis of Barrett's oesophagus. PMID- 2210463 TI - Comparison of omeprazole and cimetidine in reflux oesophagitis: symptomatic, endoscopic, and histological evaluations. AB - Symptomatic patients with endoscopically verified reflux oesophagitis were randomised to a double blind trial in which they received either omeprazole (20 mg once daily) or cimetidine (400 mg four times daily) for four, and if necessary, eight weeks. In an 'intention to treat' analysis, oesophagitis was found to have healed after four weeks in 77 of 137 (56%) in the omeprazole group and in 34 of 133 (26%) in the cimetidine group (p less than 0.001). By eight weeks these values were 71% and 35% respectively; p less than 0.001. Histological assessments were available for 73% of the patients. At entry, 63% (66 of 104) in the omeprazole group and 60% (56 of 94) in the cimetidine group (ns) had abnormal histology. After the study, the proportions of patients who initially had had abnormal histology but who then progressed to normal were 67% (44 of 66: omeprazole) and 48% (27 of 56: cimetidine) respectively (p less than 0.001). All patients had reflux symptoms at entry. After four weeks, 46% in the omeprazole group and 22% (p less than 0.001) in the cimetidine group were asymptomatic. Diary cards completed for the first two weeks showed that patients treated with omeprazole experienced fewer reflux symptoms by day and night and used fewer antacids. Omeprazole, 20 mg once a day for four to eight weeks, healed a greater proportion of patients with reflux oesophagitis than cimetidine, 1.6 g per day, assessed endoscopically and histologically, and relieved more patients' symptoms. PMID- 2210464 TI - Reduction of gastric ulcer recurrence after suppression of Helicobacter pylori by cefixime. AB - The effect on the recurrence of gastric ulcers after suppression of Helicobacter pylori by combined treatment with cimetidine and the antimicrobial drug cefixime was investigated. Twenty one of 43 patients with endoscopically proved gastric ulcer and H pylori infection were randomly assigned to receive cimetidine 800 mg daily for 12 weeks; the remaining 22 patients received cimetidine 800 mg daily for 12 weeks plus cefixime 100 mg daily for the last two weeks. After treatment, 88% of 17 patients on cimetidine only remained H pylori positive, whereas combined administration of cimetidine and cefixime had suppressed H pylori in 78% of 18 patients (p less than 0.05). Seventeen patients in the former group whose ulcers healed but who remained H pylori positive and 18 patients in the latter group whose ulcers healed and who were no longer infected with H pylori continued to be followed after treatment. These patients underwent endoscopy to detect ulcer recurrence if symptomatic, or at 12 and 24 weeks if asymptomatic. At 12 weeks, recurrence was observed in seven of 15 (47%) patients in whom H pylori persisted, but in only one of 14 (7%) patients in whom H pylori had been suppressed (p less than 0.05). At 24 weeks, however, recurrence rates were similar between the two groups. These findings indicate that H pylori infection may be closely related to early ulcer recurrence. PMID- 2210465 TI - High grade dysplasia of the gastric mucosa: a marker for gastric carcinoma. AB - The natural history of gastric epithelial dysplasia and its relation to gastric cancer are ill defined. A consecutive series of 40 patients with an initial diagnosis of gastric epithelial dysplasia based on examination of endoscopic biopsies has been reviewed to determine the clinical outcome and to evaluate a two tier histological grading system as a predictor of the risk of cancer. On review, only 20 of the 40 patients were considered to have true dysplasia: seven patients had low grade dysplasia and 13 had high grade dysplasia. Of the 13 patients with high grade dysplasia, 11 (85%) were found to have gastric cancer within 15 months. Of the 10 patients with high grade dysplasia who underwent gastrectomy, six were found to have early gastric cancer, three had cancer invading into the muscularis propria, and none had lymph node metastases. High grade dysplasia is thus a marker of gastric cancer. Moreover, the cancers associated with high grade dysplasia are usually pathologically favourable and curable. The finding, by an experienced pathologist, of high grade dysplasia in two separate sets of endoscopic biopsies is therefore an indication for radical surgical treatment, provided that the patient's age and general condition permit such an approach. PMID- 2210466 TI - Myoelectrical activity of the Billroth II gastric remnant. AB - This study was undertaken to investigate the extent to which gastric electrical control activity and phasic contractile activity are preserved after Billroth II resection and to assess the relation between these activities and postprandial symptoms in patients who have undergone Billroth II resection. Thirty three patients were studied after Billroth II resection without vagotomy. Gastric electrical activity was recorded from surface electrodes and intraluminal pressure was recorded simultaneously. The electrogastrographic signals were analysed by Running Spectrum Analysis. In addition, three dogs with a Billroth II stomach and implanted serosal electrodes were studied. Phasic gastric pressure waves were observed in most patients. Electrogastrographic signals recorded from 82% of the Billroth II patients contained a mean (SD) peak at 3.1 (0.2) cycles per minute (cpm). Fasting and postprandial frequencies correlated significantly (p less than 0.02) with the score for nausea and vomiting. In 61% of the patients, the electrogastrographic signal contained a stable component with a frequency of 10.5 (0.6) cpm that was not caused by respiration. We suggest that this activity is of intestinal origin. In all three dogs studied, retrograde conduction of jejunal electrical control activity (16 cpm) into the distal part of the gastric remnant was observed. In the Billroth II patients, the presence of a 10 cpm component correlated negatively with symptoms. PMID- 2210467 TI - Towards a true prevalence of peptic ulcer: the Sorreisa gastrointestinal disorder study. AB - This study, designed to overcome methodological problems inherent in earlier prevalence studies of peptic ulcer, was carried out in a municipality in northern Norway. It included the total population of 2027, aged 20-69 years, and comprised a questionnaire and search for previously diagnosed peptic ulcers in the local medical records for all subjects, and additional endoscopy of all subjects with dyspepsia and their matched healthy controls (n = 619). The overall prevalence was 10.5% in men and 9.5% in women, a sex ratio close to one and a higher duodenal:gastric ratio than previously reported from this region. A substantial 1% prevalence of asymptomatic ulcers was also observed. PMID- 2210468 TI - Duodenal ulcer is associated with low dietary linoleic acid intake. AB - It has been suggested that the falling incidence and virulence of duodenal ulcer is related to increased dietary polyunsaturated essential fatty acid intake. The adipose fatty acid profile, which closely reflects dietary intake, was measured in 35 men with chronic duodenal ulcer and 35 matched control men. The mean percentage of linoleic acid in adipose tissue was significantly lower in the ulcer group (10.0 (0.7) v 12.3 (0.7)%, p less than 0.01) and this difference was found in both smokers and non-smokers. This finding suggests that the diets of duodenal ulcer patients are deficient in linoleic acid and this could be of aetiological importance. PMID- 2210469 TI - Adjuvant antibiotic therapy in duodenal ulcers treated with colloidal bismuth subcitrate. AB - Persistence of Helicobacter pylori after duodenal ulcer healing is associated with high rates of ulcer relapse. We compared colloidal bismuth subcitrate alone with CBS combined with one of four antibiotic regimens in the treatment of duodenal ulcers. Endoscopy and antral biopsies were performed before treatment and four weeks afterwards. Biopsy specimens were examined for histological evidence of gastritis and by Gram stain and culture for H pylori infection. Altogether 141 patients were allocated to one of five treatment groups. Giving CBS and metronidazole (400 mg tid for 7 days) with and without amoxycillin (500 mg tid) achieved higher clearance rates of H pylori than treatment with CBS alone (p less than 0.01). These two combinations also achieved higher rates of antral gastritis healing than CBS alone (p less than 0.01 and p less than 0.05 respectively). Susceptibility to metronidazole was tested in 29 isolates before and in seven isolates after treatment with metronidazole by disc diffusion test and minimum inhibitory concentration assay. Twenty seven (93%) of the isolates were sensitive before treatment while six of seven (86%) were resistant afterwards. Four of the six resistant strains had acquired resistance during treatment and one of these had acquired metronidazole resistance despite concomitant treatment with amoxycillin, to which it remained sensitive. CBS with adjuvant metronidazole at a dose of 400 mg tid for seven days significantly improves the eradication of H pylori compared with CBS alone. Acquired metronidazole resistance, however, seems to be an important cause of failure to eradicate H pylori. PMID- 2210471 TI - [Indications for and results of in-vitro fertilization (IVF), intratubal gamete- (GIFT) and embryo transfer (EIFT)]. PMID- 2210470 TI - [Reproduction medicine]. PMID- 2210472 TI - [Indications for and results of microsurgical procedures for the treatment of female sterility]. PMID- 2210473 TI - [Andrological study methods and therapeutic principles in male sterility factors]. PMID- 2210474 TI - [Gynecologic-andrologic interaction. Childlessness as long-term problem]. PMID- 2210475 TI - [Current diagnostic and therapeutic procedures in reproduction medicine. Salpingoscopy and surgical hysteroscopy]. PMID- 2210476 TI - [The psychological status of women with frustrated wish for children]. PMID- 2210477 TI - [Clinical evaluation of newer procedures in reproduction medicine]. PMID- 2210478 TI - [Research in reproduction medicine]. PMID- 2210479 TI - [Justified and unjustified fears in reproduction medicine]. PMID- 2210480 TI - [Electrocardiography in elderly inhabitants of Krakow. Epidemiological study]. AB - The electrocardiographic records were performed in the randomly chosen area of Cracow. The results were obtained from 512 persons (153 M and 359 F) aged 70-93 years. Normal electrocardiograms observed in 25.4% of the studied population. The prevalence of electrocardiographic abnormalities was as follows: ST segment depression--40.0%, patterns of infarction--17.2% and left ventricular hypertrophy -10.4%. On the contrary right axis deviation, bradycardia, sinus arrest, II and III of a-v blocks were rarely observed. The prevalence of electrocardiographic abnormalities in the aged in Cracow is in the accordance with the findings observed in the countries with high risk of cardiovascular diseases. PMID- 2210481 TI - [Chemical poisoning in suicide attempts by the elderly]. AB - The problem of suicidal attempts in which the chemical substances are used is very important for clinical toxicology. Suicide subjects make up 61 to 68% of all hospitalized patients with acute poisoning in Toxicological Centers in Poland. And mainly the young not the old are involved in these suicidal attempts. In the Toxicological Clinic in Krakow in period 1980-1986 138 patients (81 women and 57 men) above the age of 60 residing in Province of Krakow were hospitalized since while committing suicide by chemical substances, they got poisoned. Most of the patients (90%) were poisoned by a single drug or mixed ones; frequently by Reladorm (31.5%), by benzodiazepines alone (31%) and by barbiturates (21%), less frequently by chlorpromazine drugs, tricyclic antidepressants and cardiac drugs which were only concomitant toxins. The rest of the studied patients (10%) were poisoned with organic solvents (4 patients), hydrochloric acid (4 patients), organophosphate pesticides (3 patients). In single cases it was seed dressing T (thiuram), carbon monoxide or ethanol poisoning. The case of ethyl alcohol poisoning was discussed and the patient who ingested it commit suicide died. 14 patients died (10%) and the lowest mortality rate was in 61-70-year--old patients and it was evidently higher for the younger patients. The causes of the patients' death as well as psychological and psychiatric aspect of the suicides were discussed. Some conclusions concerning prophylaxis of suicidal poisonings in the elderly were drawn. PMID- 2210482 TI - [Metabolism of potassium in the acute phase of myocardial infarction]. AB - The aim of the study was to evaluate changes in potassium level at 1 to 4 days in patients with acute myocardial infarction. The studies comprised 103 patients including 85 men and 18 women, aged from 31 to 90 years (mean age 56.7 +/- 11.7). A control group consisted of 51 patients (40 men, 11 women) aged from 34 to 74 years (mean = 56.7 +/- 10.7) on intensive diuretic therapy due to heart failure without myocardial infarction. In order to establish our own normal limits of potassium level in the blood serum and erythrocytes 20 healthy subjects (10 men, 10 women) aged 34 to 54 years (mean = 37.8 +/- 9.1) were studied. In patients with acute myocardial infarction and in control subjects serum potassium levels (Ks), erythrocyte potassium content (Ke) and urine potassium level (Ku) had been determined. Serum and erythrocyte potassium levels were assessed by Mayer method with the use of flame photometer. Urine potassium level was also determined by flame photometry. Values of serum and erythrocyte potassium level were given in mmol/l, and urine potassium levels in mmol/h. Ks, Ke and Ku values at 1 to 4 days were compared with one other and with levels in the control group and in healthy subjects as well as with values assumed as normal. At 1 day of the myocardial infarction Ks-3.87 +/- 0.58 mmol/l was significantly lower as compared with Ks at 2, 3 and 4 days and with values in the control group: Ks = 4.4 +/- 0.49 mmol/l and in healthy subjects: Ks = 4.2 +/- 0.36 mmol/l (p less than 0.0001). Ke levels at 1 and 2 days were 98.3 +/- 5.6; 99.2 +/- 5.3 mmol/l; significantly lower as compared with the levels at 4 days (Ke = 102.5 +/- 5.8 mmol/l p less than 0.05) and as compared with the levels in the control group: Ke = 104.5 +/- 6.1 mmol/l (p less than 0.05) and in healthy subjects: Ke-102.6 +/- 5.8 mmol/l (p less than 0.01). In contrast Ku level at 1 day of the infarction was 4.6 +/- 3.2 mmol/h and it was significantly higher as compared with excretion levels on the remaining days and in the control group: Ku = 2.7 +/- 0.7 mmol/h (p less than 0.0001). The present studies show changes in the potassium level in the acute phase of the myocardial infarction consisting in a decrease of Ks and Ke levels and an increase in Ku level, mainly at 1 day of the infarction. PMID- 2210483 TI - [Clinical and morphological picture of adrenal gland carcinoma with characteristics of early embryonal development]. AB - A two year old girl with symptoms of virilization was investigated and an adrenal gland tumor with morphological sings of malignancy was diagnosed. After surgery, irradiation and chemotherapy, a complete recovery was observed. The authors point out the diagnostical difficulties in similar cases. Our observation seems to confirm earlier suggestions, that in cases with predominant androgen activity the better prognosis is expected. PMID- 2210484 TI - [The role of cholecystokinin receptors in the regulation of the circulation and oxygen consumption in the pancreas]. AB - These studies were conducted to assess whether cholecystokinin (CCK) receptors play a role in the regulation of pancreatic vascular, metabolic and secretory responses. In anesthetized dogs, the superior pancreatico-duodenal artery blood flow (SPBF), pancreatic microcirculatory blood flow (PBF), pancreatic oxygen consumption, bicarbonate and protein output were determined. Control SPBF, PVO2 and PBF averaged 35.6 ml/min, 1.9 ml/min-100 g and 56 ml/min-100 g respectively. CCK-8 was infused intraarterially in doses of 12.5, 25 and 50 pM/kg-h. SPBF increased by 13, 21 and 43%, PBF increased by 17, 29 and 53% and PVO2 increased by 10, 15 and 38% respectively. With 10% bite + oleic acid placed in the intestinal lumen SPBF increased by 11%, PVO2 by 27% and PBF by 17% respectively. CCK and oleic acid + bile significantly increased pancreatic secretory activity. Pretreatment with a highly selective CCK receptor antagonist L-364 (1 mg/kg i.v.) abolished the circulatory, metabolic and secretory responses to CCK and significantly reduced these responses to luminal oleic acid and bile. These results suggest that the CCK receptors of the pancreas may be involved in the food-induced increases in the pancreatic blood flow, oxygen consumption and exocrine secretion. PMID- 2210485 TI - [Binding of various polycyclic aromatic hydrocarbons (PAH) by plasma albumin and blood cells]. AB - We have studied in vivo and in vitro partition of pyrene, fluoranthene and benz(a)anthracene (BaA) between blood cells and plasma or phosphate buffer pH 7.4 and their binding to bovine serum albumin. The level of PAH in blood and plasma was determined in rats after i.v. administration of pyrene, fluoranthene and BaA in dose 20 mg/kg by gas chromatography method. In vitro 20 micrograms of PAH was added to blood samples or blood cell suspension. These samples were incubated at 37 degrees C. After 1 hr the concentration of PAH in blood cell and plasma or buffer was determined. The data indicate that whole pyrene and fluoranthene are distributed to blood cells. 39% of BaA in whole blood is present in blood cells and 56.9% in plasma. Plasma protein binding of PAH were determined by gel filtration 0.4 cm3 of PAH-protein solution was given on a Sephadex column. PAH binding parameters were obtained from simple linear regression of Scatchard plots of the data. In a albumin solution (0.4%) the number of binding sites was 2 for BaA, 3 for pyrene and 11 for fluoranthene. The binding constants for BaA, fluoranthene and pyrene were 0.17; 0.71 and 1.11 mol-1 X 10(4), respectively. PMID- 2210486 TI - [Creams protective against electrolytes--evaluation of protection in vitro]. AB - Diffusion-inhibiting effect of the barrier creams in case of some electrolytes i. e. alkalies, acids, salts of alkaline metals, and salts of heavy metals in two chambers diffusion apparatus have been determined. Protection efficiency of two own creams and two reference creams (silicone Goldschmidt's cream, Essen FRG, and "Anthydro" made by Phypro Laboratories 86270 La Roche, Posay, France) were compared. High protection efficiency of own creams, especially in case of sulfuric acid, hydrochloric acid, sodium nitrite, potassium bichromate and nickel nitrate was found. Diffusion of potassium hydroxide and sodium hydroxide did not exceed 2% of control values during 4 hrs period. PMID- 2210487 TI - [A study on the relationship between natriuresis and renally formed dopamine in the rat]. AB - This study was undertaken to elucidate the relationship between natriuresis and renally formed dopamine in pentobarbital-anesthetized rats that were loaded with 0.9% NaCl. Infusion of dopamine resulted in marked increases in urinary free dopamine excretion, plasma free dopamine concentration, urine volume and urinary sodium excretion. Infusion of carbidopa markedly decreased urinary free dopamine excretion, but did not affect urine volume and urinary sodium excretion. Infusion of L-dopa markedly increased urinary free dopamine excretion and plasma free dopamine concentration, but did not affect urine volume and urinary sodium excretion. When carbidopa was infused with L-dopa or dopamine, carbidopa significantly inhibited the increase in urinary and plasma free dopamine induced by L-dopa, but did not inhibit the increases in urinary and plasma free dopamine, urinary sodium excretion and urine volume induced by dopamine. These data indicated that there is no correlation between renally formed dopamine and natriuresis, and furthermore suggested that renally formed dopamine is not essential for natriuresis. PMID- 2210488 TI - [A new system for the measurement and analysis of motor activity in mice: effect of several central stimulants]. AB - To estimate the spontaneous motor activity in mice, a new system with highly stable sensitivity and good reproducibility was made, and the effects of five central stimulants were investigated. The apparatus consists of a doughnut-shaped cage with detectors for measuring spontaneous motor activity; i.e., the number of movements, vertical activity, total distance, etc., for every five min. Methamphetamine (0.5, 1 and 2 mg/kg, s.c.) produced an increase in the number of movement and markedly increased total distance. Cocaine (20, 50 and 75 mg/kg, s.c.) caused a marked increase in movement and total distance. Mice injected with 50 mg/kg of cocaine showed long-lasting locomotion with few stops throughout the observation period. Caffeine (10, 30 and 100 mg/kg, s.c.) produced a long-lasting and moderate excitation. Morphine (5, 10 and 20 mg/kg, s.c.) caused a marked increase in continuous locomotion dose-dependently. Apomorphine produced a transient increase in rearing and locomotion at a dose of 1 mg/kg, s.c.; and it produced long-lasting rearing and moderate locomotor activity at 3 mg/kg. These results suggest that this apparatus is able to detect characteristic changes in spontaneous motor activity produced by central stimulants and may be useful for analyzing drug-induced motor activity in mice in more detail. PMID- 2210489 TI - Lytic effect of Vibrio cholerae elastase on gram-positive and -negative bacteria. AB - Elastase of Vibrio cholerae caused the lysis of freshly grown cells of Gram negative (Pseudomonas aeruginosa, Proteus vulgaris, Salmonella paratyphi A and Klebsiella pneumoniae) bacteria. Gram-positive (Staphylococcus aureus and S. epidermidis) organisms were resistant to this enzyme. Heat killed and lyophilized Gram-positive and -negative bacteria (except S. aureus and S. epidermidis) showed higher sensitivity to elastase. Both Gram-negative and -positive bacteria were lyzed maximally by elastase at pH 8.0. At this pH, lytic activity of elastase was maximum in Tris-HCl and glycine-NaOH buffers followed by Tris-maleate and cacodylate buffers. PMID- 2210490 TI - Enzyme synthesis of L-tryptophan. AB - Enzyme synthesis of tryptophan from indole, pyruvate and ammonium salts was studied using Escherichia coli cells exhibiting a significant tryptophanase activity. In addition to the effect of cultivation medium composition and cultivation conditions, factors affecting the course of the conversion were investigated. Production of 32.4 g/L of L-tryptophan was reached after 48 h under optimal conditions. PMID- 2210491 TI - Transport of L-tryptophan in Saccharomyces cerevisiae. AB - In addition to the general amino acid transport system (GAP) of S. cerevisiae L tryptophan is transported by another system with approximately 25% capacity of GAP, with a KT of 0.41 +/- 0.08 mmol/L and with a similar specificity as GAP (lower inhibition by Met, Pro, Ser, Thr and 2-aminoisobutyric acid; greater inhibition by Glu and His). The pH optimum of this system is at 5.0-5.5, activation energy above the transition point (20 degrees C) was 20 kJ/mol, below the transition point 55 kJ/mol. The transport by this system was virtually unidirectional, efflux amounting to at most 10% into a tryptophan-free medium. The transport itself was blocked by 2,4-dinitrophenol, antimycin A and uranyl nitrate. The system was synthesized de novo during preincubation with glucose = fructose greater than trehalose greater than ethanol within 30 min, and was degraded with a half-time of 15 min in the absence of further synthesis. The accumulation ratios of L-tryptophan in gap1 mutants were concentration-dependent (200:1 at 1 mumol L-Trp/L, 4:1 at 2.5 mmol L-Trp/L) and decreased with increasing suspension density from 200:1 to 5:1 (for 10 mumol L-Trp/L). The involvement of hydrogen ions in the uptake was clearly demonstrated by the effect of D2O even if it could not be established by either shifts of pHout or membrane depolarization. PMID- 2210492 TI - Observations on bacteria associated with pigeon crop. AB - Lactobacilli, streptococci and coliforms of pigeon crop contents, 5th wash, macerate and those of first-day pigeon milk have been studied. Streptococci predominated in all the samples tested. Relatively higher counts of lactobacilli and streptococci in crop macerate than in the 5th wash suggested the adhesion of these bacteria to crop wall. Because of frequent occurrence in crop of partially digested fibrous food, its contents were tested for the presence of cellulolytic bacteria. The results indicated that four isolates were capable of utilizing cellulose with the resultant production of reducing sugars. It is inferred that the crop microflora is involved in the degradation of dietary fibre in the pigeon. PMID- 2210493 TI - Distribution of cells in different stages of the cell cycle and some age-related physiological characteristics in dependence on the dilution rate in chemostat cultures of Candida utilis. AB - Position of cells in their cell cycle was determined microscopically in chemostat cultures of Candida utilis. Proportion of cells in phase G1 decreased in a linear manner from 86% to 58% with dilution rate. Proportion of cells in phase S increased in the same range of D from 5.6 to 13.5% and in the (G2 + M) phase from 8.4 to 28.5%, again linearly. Differential centrifugation was used to separate chemostat cultures to mother and daughter cells. Analyses showed that, relative to mother cells, daughter cells contain 2.1-11.9% more protein and 25.5-34.6% more RNA in dry matter. Their mass is 34.4-5.6% lower and volume is 154-19% smaller. PMID- 2210494 TI - Continuous growth of Candida utilis under periodic change of growth-limiting substrate. AB - A periodic change of limitation by glucose and ammonia was effected during continuous cultivation of Candida utilis. Values of feed parameters providing periodic nitrogen limitation were established. Cell biomass yield, macromolecular composition and parameters of individual cells (cell mass, budding percentage and cell-wall polysaccharide per surface square unit) were examined. The cyclic regime was found to result in culture synchrony. Parameters obtained on the basis of cell counts displayed a high sensitivity to changes in limitation where as the remaining parameters were less sensible. PMID- 2210495 TI - Cyclical changes in the pituitary gonadotrophs (GTH cells) in relation to the testicular cycle in Puntius sarana (Hamilton). AB - The pituitary gland of Puntius sarana is of the leptobasic type and has three subdivisions--a proximal pars distalis (PPD), a rostral pars distalis (RPD) and a pars intermedia (PI) arranged vertically one below the other. The gonadotrophs (GTH cells) of the PPD were identified by their PAS, ATh, AF, aniline blue and alcian blue positivity and by their immunoreactivity to ovine anti-LH beta subunit, anti-salmon GTH and anti-silver carp GTH. The testes of Puntius sarana have been classified as the "unrestricted type". The morphological, histological and histometric findings indicate that the testing passes through four distinct stages--preparatory, fully mature, spawning and spent. Spermatogenesis begins in January and continues up to July. The spawning season lasts from late July until October. Cyclical changes in the gonadotrophs correlate well with changes in the testes. The histometric data show that the GTH cells attain maximum values (size and number) during the breeding season. The peak values for testicular weight, lobule diameter, the gonadosomatic index (GSI) and the sperm concentration in the testes, and the number, size and amount of secretory material in the cytoplasm of the gonadotrophs, coincide with the time of maximum environmental temperature and the longest days. PMID- 2210496 TI - Formation of multiple ependymas in the regenerating optic lobe of larvae of the Egyptian toad, Bufo regularis Reuss. AB - In the regenerating optic lobe of Bufo regularis larvae, secondary ependymas were formed in both the dorsal part (optic tectum) and ventral region (tegmentum) of the lobe concerned. These secondary ependymas were frequently observed in the rostral and caudal tectal regions after complete excision of the tectum. Most of the multiple ependymal structures were formed by self-organization of groups of undifferentiated cells migrating from the primary ependyma lining the optic tectum. Others split off from the primary ependyma, but remained in contact with it. The observations emphasize the wide range of possibilities of the cells produced by the larval tectal ependyma in response to partial or total excision of the tectum. The results suggest that cells of ependymal origin, in regenerating tectum, are capable of self-organization to complete ependymal tubes in the absence of direct with the primary ependyma. PMID- 2210497 TI - Experimental ischaemia of the vertebral artery and its effect on brain stem auditory evoked responses in guinea pigs. AB - The aim of the study was to examine the effect of artificial ischaemia of the vertebral artery region on brain stem evoked auditory potentials (BAEP) in guinea pigs. The results indicate that BAEP are influenced mainly by unilateral irritation of the vertebral artery. An increase in the audibility threshold was observed in the experimental guinea pigs in group C (an increase of 10-40 dB on the side of irritation of the vertebral artery and of 10 dB on the opposite side). Lengthening of the latency period of the P2 wave and of the conduction period between waves P1 and P5 was also observed. PMID- 2210498 TI - New approaches to the neuron theory. PMID- 2210499 TI - Interrelationships of B- and T-cell areas in peripheral immune organs of the albino rat after hind limb autotransplantation. AB - Using 68 3-month-old male albino rats, it was established that the pattern of the changing interrelationships of B- and T-cell areas in the spleen and in the popliteal, inguinal and medial iliac lymph nodes regional for the experimental limb during the initial stage after hind limb autotransplantation, with or without sciatic nerve alloplasty, represents a universal type of initial response of the peripheral immune organs to external challenge which takes place in three steps: 1) an increase in the number and size of the lymph nodules, 2) enlargement of T-cell areas, 3) an increase in the number of structures containing antibody forming cells (the medullary cords in the lymph nodes and the splenic cords). Sciatic nerve alloplasty gives rise to expansion of the medullary cords in the lymph nodes and the marginal zone and cords in the spleen, with parallel significant enlargement of T-cell areas. PMID- 2210500 TI - Ultrastructural changes in the blood capillaries of the spinotrapezoideus muscle and pancreas of albino rats during experimental dehydration. PMID- 2210501 TI - The influence of balneological factors on lymph node morphology. PMID- 2210502 TI - Interorganic nerve connections. PMID- 2210503 TI - Studies on the structure, histology and histochemistry of the hepatopancreas of the parasitic isopod Nerocila serra Schioedte et Meinert 1881, from the Waltair Coast. AB - In Nerocila serra, three pairs of hepatopancreatic caeca lie on either side of the digestive tract. Each of the tubules is composed of two types of cells-a type with vacuoles and a type without; they have secretory and absorptive function. Histochemical tests of the hepatopancreas revealed the presence of strongly acidic, weakly acidic, sulphated and carboxylated substances. It is suggested that the gland cells contain large amount of proteins, lipids and phospholipids. PMID- 2210504 TI - Effect of juvenile hormone on Musca domestica vicina Macq. II. The gonotrophic cycle. AB - The effect of the topical application of the synthetic juvenile hormone JH-I on adult specimens of Musca domestica vicina Macq was studied. The adult stage responded to different JH-I concentrations in different ways. The gonotrophic cycle was shortened, the number of eggs decreased and the hatching rate was reduced. The adults of the next generation displayed a number of anomalies. The ovarian amino acid concentrations varied considerably according to the dose of JH I and the stage of maturation of the relevant ovary. PMID- 2210505 TI - Morphology and anatomy of the olfactory organs of the marine fish Thynnus thunnina (Cuv. et Val.). AB - The authors studied the morphology and anatomy of the olfactory organs of the marine fish Thynnus thunnina. The fish has a single nasal orifice. The round olfactory rosette has a central axis surrounded by radially oriented lamellae. The olfactory rosette (olfactory organ) is provided with two accessory nasal sacs - a lacrimal and an ethmoidal sac. Thynnus thunnina was classified in Teichmann's (1954) group II, i.e., the "eye-fishes", whose vision is better developed than their olfaction. PMID- 2210506 TI - Neurosecretory cells in Diptera. AB - The neurosecretory cells were studied in 20 dipteran species belonging to three suborders. The NSC are localized in (a) the frontal ganglion (in 10 of the 20 species studied), (b) the pars intercerebralis region of the protocerebrum (in the median and lateral groups), (c) the tritocerebral region of the brain (in 8 of the 20 species studied) and (d) the suboesophageal ganglion. In one species, NSC were also seen in the prothoracic ganglion. The NSC were classified as types A, B and C/D. The NSC of the median group of the pars intercerebralis were unusually large compared with the size of the brain. The number, size and distribution of the cells are discussed. PMID- 2210507 TI - Malformations of the regenerating optic tectum of larvae of the Egyptian toad, Bufo regularis Reuss. AB - Morphological and histological abnormalities were observed in the regenerating optic tecta of Bufo regularis larvae after partial excision of the left tectum and total excision of the right tectum. They were found in both the left and the right tectum. Invagination of the tectal tissue into the optic ventricle, masses of blood capillaries and gaps or cavities in the tectal tissue were observed. The size of the optic tecta was reduced and the shape and structure of the dorsal aspect of the midbrain were highly anomalous. PMID- 2210508 TI - Postnatal development of the rat oviductal epithelium. AB - Submicroscopic examination of rat oviducts in the early postnatal period showed that the character of the epithelium remained relatively indifferent up to the 6th day. Typical findings in this phase include an apical migration of the centrioles, with subsequent formation of solitary cilia; ciliated cells were an isolated occurrence. Ciliogenesis in the rat oviductal epithelium starts between the 8th and the 10th day. A continuous kinociliary apparatus is formed on the basis of centriole replication. The first secretory and peg cells appear towards the end of the second week. PMID- 2210509 TI - Changes in the proportion of free and bound ribosomes in the syncytiotrophoblast of normal human placenta during pregnancy. AB - Samples of normal human placental tissue from the first and second trimester and the end of pregnancy were processed for electron microscopy. The ratio of free to bound ribosomes in the syncytiotrophoblast was determined by the point-counting method in photographs giving a 45,000-fold final magnification. The ratio of free to bound ribosomes was found to be significantly higher at 9-11 weeks than at 6-8 weeks and to be significantly lower at 12-14 weeks than at 9-11 weeks. No significant differences were found between the 12th to 14th week and the 20th to 25th week. These data were compared with the ratio of free to bound ribosomes in different regions of the placenta at the end of pregnancy. PMID- 2210510 TI - Contribution to knowledge of the morphogenesis of the nasal apparatus of the domestic sheep (Ovis aries L.). AB - The author studied the morphogenesis of the nasal apparatus in a sheep (Ovis aries L.) embryo with a length of 57 mm, at the optimum stage of development of the chondrocranium, as a part of his studies of development of the nasal apparatus in ungulates. The nasal apparatus is in general constructed according to the general scheme for mammals. Attention is drawn to the development of the superior alar cartilage, which is reminiscent of the situation in reptiles, to the strikingly developed atriturbinale auctorum (the author does not agree with this morphological designation, which is reserved for the vestibular turbinale in birds), to the well developed anterior paraseptal complex, to the extremely large maxilloturbinale and to the massive trunk of the ethmoturbinale I, which suppresses the corresponding recesses. The olfactory labyrinth is developed at three levels, the upper (rostral) level corresponding to the frontoturbinalia region, the middle to the ethmoturbinale I and the third (caudal) level to the region of the ethmoturbinalia II, III and IV (the recessus ethmoturbinalis). There is no foramen epiphaniale, no crista semicircularis and no crista Galli. A posterior paraseptal cartilage is present; in the author's opinion it is joined to the lamina orbitonasalis and not to the lamina transversalis post., since the latter is absent. PMID- 2210511 TI - Morphogenesis of the nasal apparatus of the red deer (Cervus elaphus L.). AB - Three stages of morphogenesis of the nasal apparatus of the red deer (Cervus elaphus L.) were studied. Many ancestral traits reminiscent of relationships in other mammals and even in reptiles were found, including a cart, ectochoanalis, paraseptal cartilages, the septum nasi and its ventral trabecular enlargement, a lamina transversalis ant., clear separation of the cart, parietotectalis and cart, paranasalis from each other and a crista semicircularis. A maxilloturbinale, was present, but not a nasoturbinale. The main specific features were a completely rostrally localized, peculiar cartilaginous structure in the preseptal space, for which there is as yet no morphological explanation, and pronounced bulging of the cartilaginous wall of the nasal capsule in a ventrolateral direction, level with the rostral region of the olfactory labyrinth (caudally to the aboral end of the maxilloturbinale). In the early stages of morphogenesis, it was found that the ethmoturbinalia might be formed by fusion of the edges of the anlagen of the paranasal cartilage and the lamina orbitonasalis. The structure of the olfactory labyrinth was reminiscent of its organization in the sheep embryo; the recessus frontalis was completed by a series of frontoturbinal recesses and frontoturbinalia, which are poorly developed in the red deer, however. The floor of the caudal part of the nasal capsule was very little developed and there was no cart, paraseptalis post. PMID- 2210512 TI - Re-examination of potassium sorbate and sodium sorbate for possible genotoxic potential. AB - Potassium sorbate and sodium sorbate were investigated for possible genotoxic actions using the Salmonella/mammalian-microsome test, HGPRT and sister chromatid exchange (SCE) test with Chinese hamster ovary cells, the micronucleus test on bone marrow cells of mice and Chinese hamsters, and the chromosome aberration and SCE test on Chinese hamsters. In all the in vitro tests no signs of genotoxicity were detected. Whereas no in vivo mutagenicity of potassium sorbate and sodium sorbate with freshly prepared aqueous solutions and with stored potassium sorbate was found, investigations with stored sodium sorbate revealed weak clastogenic activity by increased chromosome aberrations and elevated numbers of micronuclei at doses of 200 mg/kg body weight, but no induction of SCEs. PMID- 2210513 TI - Hepatic peroxisomal and microsomal enzyme induction by citral and linalool in rats. AB - The short-term effects of oral administration of citral and linalool to rats have been compared. Male Wistar rats were given, by gastric intubation, 1.5 g citral or linalool/kg body weight/day for 5 days. Citral caused peroxisome proliferation as indicated by induction of cyanide-insensitive palmitoyl-CoA oxidation and bifunctional enzyme; levels of microsomal cytochrome P-450 IVA1 were also raised. Linalool caused induction of the peroxisomal enzymes but not of cytochrome P-450 IVA1, indicating that it possesses activity somewhat different from that of citral. These results suggest that the mechanisms of peroxisome proliferation may be independent of induction of cytochrome P-450 IVA1. PMID- 2210514 TI - Effect on cooking time on mutagen formation in smoke, crust and pan residue from pan-broiled pork. AB - The effect of cooking time on mutagenic activity in crust, pan residue and smoke from pan-broiled pork patties was studied in the Ames Salmonella mutagenicity test system. The effect on mutagenicity of reheating the cooked patties and of keeping them warm was also studied. The meat was broiled at 200 degrees C for various times between 2 and 10 min. Broiled meat was reheated up to 5 times at 200 degrees C, each time to a centre temperature of 70 degrees C. Reheating was also performed in a microwave oven for 2 min and in an electric oven at 200 degrees C for 10 min. In addition, broiled patties were kept warm at 60 degrees C in an incubator for up to 9 hr. The mutagenic activity increased rapidly in all fractions except the volatile phase over the first 6 min of cooking, after which time only a slight increase was seen. At cooking times below 4 min no mutagenic activity was detected in the smoke. Reheating or keeping the meat warm for up to 9 hr had very little effect on the mutagenic activity of the meat. Reversed-phase high-performance liquid chromatography mutagenicity profiles of the aerosol, crust and pan-residue extracts showed no major qualitative differences in samples cooked at different times. It is concluded that during pan broiling at 200 degrees C the major part of the mutagenic activity is formed during the first 6 min of cooking. Reheating the meat or keeping it warm does not significantly affect the mutagenic activity. No major additional mutagens are formed during continued heating for up to 25 min. PMID- 2210515 TI - Hepatic nuclear and cytoplasmic effects following intermittent feeding of rats with di(2-ethylhexyl) phthalate. AB - The effects on rats of intermittent feeding with the peroxisome proliferator and hepatocarcinogen di(2-ethylhexyl) phthalate (DEHP) have been examined. Male Wistar rats were fed for alternate 7-day periods diets containing 20,000 ppm DEHP or the control diet. The rats were examined 3 days after the start or recommencement of administration of the DEHP-containing diet or after 7 days on the control diet. After the commencement or recommencement of feeding with DEHP the expected increases in liver weight and in the number of peroxisomes were found. The increase in liver: body-weight ratio in response to administration of DEHP-containing diets was greater in rats that had been previously exposed to the compound, but re-administration of DEHP had a less marked effect on the increase in peroxisome number. Morphometric analysis showed that administration of DEHP containing diets resulted in an increase in cell number in the liver and that a fall in the cell number occurred after the rats had been returned to the control diet for 7 days. Analysis of nuclear size gave results consistent with an increase in tetraploid hepatocytes after treatment with DEHP which was reversed when the rats were returned to control diet. PMID- 2210516 TI - Comparison of the toxicity of inorganic and liver-incorporated cadmium: a 4-wk feeding study in rats. AB - The toxicity of cadmium was examined in rats fed diets containing either tissue incorporated cadmium or cadmium salt for 4 wk. The test diets contained 30 mg cadmium/kg either as cadmium chloride, or as cadmium incorporated in pigs' livers; the control group was fed a diet containing liver from a pig not treated with cadmium. Over 90% of the cadmium present in the pigs' livers was bound to metallothionein. Analysis of the diet and determination of the food consumption revealed that both cadmium-fed groups were exposed to similar dietary cadmium levels. There was no adverse effect on general health or survival. Feeding cadmium resulted in growth retardation and slightly decreased water intake. Moreover, both cadmium-treated groups showed clear signs of anaemia and increased plasma aspartate and alanine aminotransferase activities. For the group fed cadmium chloride, all of these effects were more pronounced than for the group fed cadmium incorporated in liver. Microscopic examination of the liver and kidneys, however, did not reveal any lesion that could be attributed to the cadmium treatment. After exposure to cadmium the spleen showed decreased extramedullary haematopoiesis, an effect that was also more pronounced after feeding of the cadmium chloride than after feeding liver-incorporated cadmium. The differences in the extent of the toxic effects between the inorganic and the tissue-incorporated cadmium were accompanied by differences in the cadmium concentrations in liver and kidneys: the feeding of cadmium incorporated in pigs' livers resulted in about half the accumulation of cadmium in the rats' livers that took place after intake of a diet containing cadmium chloride. In contrast a much less marked difference in cadmium accumulation was observed in the kidneys. Since humans are usually exposed to tissue-incorporated cadmium these findings deserve further investigation, with special attention to the observed difference in tissue accumulation. PMID- 2210517 TI - Percutaneous absorption of benzyl acetate through rat skin in vitro. 1. Validation of an in vitro model against in vivo data. AB - The percutaneous absorption in vitro of the fragrance agent benzyl acetate has been evaluated in flow-through diffusion cells using shaved full-thickness skin from male Fischer 344 rats. After the application of neat [methylene-14C]benzyl acetate to the epidermal surface of the skin and occlusion with parafilm 1.3 cm above the skin surface, the absorption of the chemical across the skin and into the receptor fluid was rapid and extensive, commencing within 1 hr of application, and reaching 49.8 +/- 3.2% (mean +/- SD, n = 4) of the applied dose after 48 hr. The coefficient of variation for absorption at 48 hr between four identical experiments was 6.4%. The extent of absorption at 48 hr of benzyl acetate applied in 50% (v/v) ethanol was not significantly different from that after application neat, although absorption at earlier times was enhanced, with a maximum increase of 8.5% of the applied dose at 12 hr. Over the dose range studied there was a linear relationship (r = 0.996) between the amount of benzyl acetate applied to the skin (1.66-33.13 mg benzyl acetate/cm2) and the amount absorbed into the receptor fluid at 24 hr (0.66 +/- 0.04-10.27 +/- 0.51 mg/cm2). The extent of absorption of benzyl acetate through rat skin in vitro was compared with the extent of absorption in vivo at 24 hr and a correlation coefficient of 0.993 was obtained. These data support the use of this in vitro system as a model to predict in vivo absorption and indicate the suitability of the system to study factors influencing the disposition of topically applied benzyl acetate. PMID- 2210518 TI - Renal mineralization--a ubiquitous lesion in chronic rat studies. AB - Renal mineralization is a commonly encountered lesion in old rats and its presence at times complicates the interpretation of data derived from chronic rat studies. The feeding of sucralose, a new and high-intensity sweetener under regulatory review, resulted in caecal enlargement and an increase in the incidences of renal mineralization and pelvic epithelial hyperplasia. These responses prompted a review of the literature focusing on the relationships, if any, between the caecal and renal changes. The literature supports the contention that caecal and renal changes occur frequently in response to feeding poorly absorbed osmotically active substances to rats. Some possible mechanisms that may be involved in the development of the renal lesion are discussed. PMID- 2210519 TI - The international validation of a fixed-dose procedure as an alternative to the classical LD50 test. AB - In an international study involving 33 laboratories in 11 countries, the acute oral toxicity to the rat of 20 substances and preparations was evaluated using a fixed-dose procedure and the results compared with those obtained for the test materials using the classical LD50 test. The study has shown that the fixed-dose approach to acute oral toxicity testing: (1) produces consistent results that are not substantially affected by inter-laboratory variations; (2) provides adequate information for risk assessment purposes on signs of toxicity, including their nature, time to onset, duration and outcome; (3) uses fewer animals than the current internationally agreed OECD procedure (Guideline 401-revised); (4) subjects animals to less pain and distress than the classical LD50 test and causes less compound-related mortality; and (5) enables substances and preparations to be ranked according to the EEC classification system on the basis of their acute oral toxicity, such ranking being compatible with that allocated by the results of classical LD50 studies. PMID- 2210520 TI - Three-generation reproductive study of cocoa powder in rats. AB - Male and female Sprague-Dawley rats were continuously exposed to dietary cocoa powder at levels of 0.0, 1.5, 3.5 or 5.0% for three generations. During the initial 12-wk growth periods for the F0-, F1b- and F2b-generation rats, mean methylxanthine exposures (mg/kg/day) for males/females were 30/36, 72/86 and 104/126 for the 1.5, 3.5 and 5.0% cocoa powder groups, respectively. No consistent dose-related effects on any of the monitored reproductive indices (mating, fertility, conception, gestation, viability or lactation) were noted over three generations. Minor reductions in mean body weight relative to controls at wk 12 were observed in male rats exposed to 3.5 or 5.0% cocoa powder and female rats exposed to 5.0% cocoa powder in the F1b and F2b generations. Renal tubular mineralization in the F0-generation male rats in the 5.0% cocoa powder group was the only statistically elevated histomorphological lesion observed. Plasma cholesterol concentrations in F1b-generation rats were elevated, but cocoa powder did not affect this parameter consistently across multiple generations. Thus, continuous cocoa powder consumption by rats at levels as high as 5.0% of the diet was without effect on reproductive capacity under the conditions of a standard three-generation evaluation. PMID- 2210521 TI - Stimulation of binding of benzo[a]pyrene metabolites to DNA by diet-induced peroxidative stress. AB - To investigate the influence of unsaturation of dietary fat on the oxidation of benzo[a]pyrene-7,8-dihydrodiol to DNA binding products, we fed diets containing 10% by weight of either safflower oil or lard to weanling rats. Compared with the group fed lard, the group fed safflower oil had 2.0- to 2.5-fold higher levels of unstimulated and peroxidation-stimulated activation of benzo[a]pyrene-7,8 dihydrodiol to DNA-binding metabolites, respectively, in hepatic nuclei. The rats fed safflower oil had a significant 75% higher level of lipid peroxidation as measured by the thiobarbituric acid assay. Rats fed safflower oil also showed 30% greater binding of (-)-benzo[a]pyrene-7,8-dihydrodiol oxidation products to DNA compared with animals fed lard, following administration of this dihydrodiol enantiomer through the hepatic portal vein. Significant diet-dependent differences were not apparent in DNA binding of the (+)-isomer, or in the tetrol production from either isomer; however, rats fed safflower oil showed a trend towards production of higher levels of anti-benzo[a]pyrene diol epoxide-derived tetrols. Activities of hepatic nuclear and microsomal aryl hydrocarbon hydroxylase and of cytosolic and microsomal glutathione S-transferases were not significantly affected by diet, nor was the activity of microsome-mediated binding of (+)- or (-)-benzo[a]pyrene-7,8-dihydrodiol to DNA in vitro. The results indicate that polyunsaturated fat in quantities as low as 10% by weight of the diet is sufficient to increase significantly the extent to which DNA binding metabolites of benzo[a]pyrene are produced, and that this increased metabolism is likely to be independent of mixed-function oxidases. PMID- 2210522 TI - Effects of different types of diet and sodium saccharin on proliferation at the limiting ridge of the rat forestomach. AB - Sodium saccharin, at high doses in the diet, has been reported to cause hyperplasia of the forestomach (squamous portion of stomach), at the limiting ridge in F344 rats, in addition to its potential to induce proliferative effects on the urinary bladder epithelium. We have characterized this hyperplasia of the squamous epithelium of the forestomach at the limiting ridge in F344 and Sprague Dawley rats given various doses of sodium saccharin for 4 to 95 wk. With increasing doses of sodium saccharin, the limiting ridge of the forestomach showed dose-related morphological changes: basal-cell hyperplasia, early papillary hyperplasia with basal-cell hyperplasia and papillary hyperplasia. Calcium saccharin in Prolab diet caused hyperplasia of the forestomach at the limiting ridge, similar to that caused by sodium saccharin. The severity of hyperplasia was influenced by the type of diet and by the strain of rats. AIN-76A diet without added sodium saccharin caused basal-cell hyperplasia in F344 rats, whereas Prolab, Purina and NIH-07 diets without added sodium saccharin had little or no effect on the forestomach. The effect of AIN-76A diet alone persisted through 95 wk of feeding without any evidence of tumour formation. In Sprague Dawley rats, which appeared more sensitive to effects on the forestomach than F344 rats, Prolab 3200 and Purina diets without sodium saccharin caused basal cell hyperplasia in more than half of the treated rats. The forestomach hyperplasia associated with AIN-76A or saccharin administration appears to be mild, limited in extent to the limiting ridge, and not associated with carcinogenesis. PMID- 2210523 TI - Subchronic (13-week) oral toxicity of neohesperidin dihydrochalcone in rats. AB - Neohesperidin dihydrochalcone was administered to groups of 20 male and 20 female Wistar rats at dietary levels of 0, 0.2, 1.0 and 5.0% for 91 days. No treatment related ophthalmoscopical, haematological or histopathological effects were observed. In the high-dose group, a marked caecal enlargement occurred in both sexes, accompanied by soft stools in the early stages of the study, somewhat lower plasma urea concentrations and increased plasma alkaline phosphatase activity and a decreased urinary pH. This group also showed slight growth depression accompanied by transient reduction in food intake; in males the body weights remained relatively low throughout the experimental period. Furthermore, bilirubin level was increased in females and total protein level was decreased in males of the high-dose group. The above changes were considered adaptive responses or chance effects rather than manifestations of clear toxicity. The low and intermediate- dose groups did not show any compound-related untoward effect. It was concluded that the intermediate dose, providing an overall intake of about 750 mg neohesperidin dihydrochalcone per kg body weight per day, was the no effect level. PMID- 2210524 TI - Hepatotoxicity of geniposide in rats. AB - The hepatotoxic effects of geniposide were investigated in rats. Increases in serum alanine aminotransferase and aspartate aminotransferase activities as a result of oral administration of 320 mg geniposide/kg body weight were suppressed when geniposide was administered ip or when the rats were pretreated with chloramphenicol. The non-protein sulphydryl content of the liver 4 hr after oral administration of geniposide decrease in a dose-dependent manner. Genipin, the aglycone of geniposide, had a marked reactivity with sulphydryl groups of glutathione and cysteine in vitro. The hepatotoxic effects of ip administration of genipin at a dose of 80 mg/kg body weight were comparable with those of oral administration of geniposide at a dose of 320 mg/kg. Buthionine sulphoximine pretreatment enhanced the toxicity of geniposide, while cysteine pretreatment completely suppressed it. These results suggest that the conversion of geniposide to genipin is causally related to the hepatotoxicity of geniposide and that hepatic non-protein sulphydryls are important in modulating the toxicity. PMID- 2210525 TI - Arsenic intake and excretion by Japanese adults: a 7-day duplicate diet study. AB - The amount of arsenic in the urine, faeces and in duplicate diets of two couples who had eaten customary Japanese meals were monitored for 7 days by arsine generator atomic absorption spectrophotometry. For the four volunteers, the mean daily intake of arsenic from their diets was 182 micrograms (range 27 to 376 micrograms). The dietary arsenic was composed of 5.7% inorganic arsenic, 3.6% methylarsonic acid, 27.4% dimethylarsinic acid and 47.9% trimethylarsenic compounds. The mean amounts of arsenic eliminated daily in urine and faeces were 148 micrograms (50-416 micrograms) and 46 micrograms (0-138 micrograms), respectively. The urinary arsenic was composed of 1.4% inorganic arsenic, 3.5% methylarsonic acid, 33.6% dimethylarsinic acid and 61.4% trimethylarsenic compounds. The daily intake of arsenic influenced the total amount of arsenic excreted in the urine (r = 0.7302, P less than 0.01) and the amount eliminated in the faeces (r = 0.5900, P less than 0.01) the next day. Specifically, there was also a significant correlation between the daily intakes of trimethylarsenic compounds and dimethylarsinic acid and the amounts of these compounds found in the urine the following day (r = 0.6833, P less than 0.01 and r = 0.6630, P less than 0.01, respectively). Considering the amounts of arsenic compounds present in seafood and in other components of the diet together with the urinary elimination patterns of arsenic compounds, it seemed probable that the trimethylarsenic compounds in the urine originated largely from fish and shellfish, which contain mainly arsenobetaine. Trimethylarsenic compounds in the urine should therefore be the preferred indicator of arsenic arising from the ingestion of seafood, especially fish and shellfish. In this study, the mean daily intake of inorganic arsenic from the diet (0.18 micrograms/kg) did not exceed the FAO/WHO JECFA Tolerable Daily Intake of 2 micrograms inorganic arsenic kg. PMID- 2210526 TI - Persistence of N-nitrosodiethanolamine contamination in American metal-working lubricants. AB - The potent carcinogen N-nitrosodiethanolamine (NDELA) was discovered as a contaminant of commercial metal-working lubricants over a decade ago. To determine whether or not improvements in industrial practice suggested in the meantime have eliminated this contamination from United States products, a selection of cutting fluids obtained from the current marketplace was analysed for NDELA content. All six semi-synthetic fluids examined contained NDELA at levels ranging from 0.5 to 4.3 ppm. Three of six petroleum-based lubricants and five of six synthetics also contained significant NDELA (when analysed at a detection limit of 0.03 ppm), at levels of up to 0.16 and 55 ppm, respectively. The mean concentrations were 1.5 ppm for the semi-synthetics, 0.07 ppm for the petroleum-based products, and 11.4 ppm for the synthetic metal-working fluids. While these levels are far below the values of 1-2% by weight (10,000-20,000 ppm) found in some contaminated products 13 years ago, they may nevertheless pose a continuing health risk for the machinists who work with them. PMID- 2210527 TI - Ilizarov technique in correction of foot deformities: a preliminary report. AB - Four deformed feet in three patients were corrected completely using the new limited intervention technique of Ilizarov. One foot in the younger patient was corrected by soft tissue distraction only. In three feet in the older patients V osteotomies were needed to initiate the distraction. Two complications occurred: herpes simplex infected two of the osteotomy sites, which were treated successfully with local treatment. The detailed method and indications are outlined. PMID- 2210528 TI - The use of the powered metaphyseal stapler for reconstructive procedures in the adult foot. AB - We have evaluated the Powered Metaphyseal Stapler in various procedures in the adult foot to determine the effectiveness of this form of internal fixation. Thirty-five patients had 40 operations (five bilateral). In all but one case there was both clinical and radiographic evidence of a solid bony union. Backing out of the staples has been a minor problem that has required staple removal in three patients. The Powered Metaphyseal Stapler appears to offer a most satisfactory option for internal fixation in the foot, when used in metaphyseal or cancellous bone, as either primary or adjuvant fixation. PMID- 2210529 TI - Assessment in congenital talipes equinovarus. AB - We have examined the intra- and interobserver repeatability of several measurements of the original deformity and the postoperative correction in children with congenital talipes equinovarus deformity. A neonatal photograph and a preoperative soft tissue radiograph had acceptable repeatability as a method of early assessment. The postoperative range of movement measured by goniometer was adequate for one examiner, (mean: 2-6 degrees), but poor between examiners (mean: 5-14 degrees). Postoperative radiographic measurement between observers was more repeatable than the range of movement. The combined talocalcaneal angle had good repeatability in young children. PMID- 2210530 TI - Fibular mobility in chronic lateral instability of the ankle. AB - Using roentgen stereophotogrammetric analysis we recorded the mobility of the lateral malleolus under maximum passive plantarflexion and dorsiflexion and during the anterior drawer and the adduction tests in 29 patients with chronic lateral instability of the ankle. Medial and anterior displacements were observed during plantarflexion, at the adduction test and at the posterior loading of the tibia. At dorsiflexion we recorded posterior fibular shifts. The simultaneously occurring fibular rotations were small. Chronic lateral instability of the ankle was associated with slightly increased fibular movements during plantarflexion and dorsiflexion, and at the adduction test in some patients with bilateral symptoms, perhaps reflecting a generalized joint laxity. PMID- 2210531 TI - Elongation and forces of ankle ligaments in a physiological range of motion. AB - The purposes of this study were: (1) to measure the distances between the insertion sites of selected ankle ligament fibers, (2) to measure the force elongation characteristics of isolated bone-ligament-bone preparations, and (3) to relate the force measurements to angular positions of the ankle. The findings can be used to discuss clinically the correlation between possible ligament injuries and associated foot movement. Three fresh cadaveric ankles were dissected to expose the anterior talofibular ligament, the calcaneofibular ligament, and the superficial deltoid ligament. The ankles were first mounted on a fixture, and insertion to insertion distances of the ligament fibers were measured for selected positions of the ankle/subtalar joint. Bone-ligament-bone preparations were then removed, returned to their anatomical length and uniaxial force-extension testing was performed. The forces in each ligament were recorded for distances corresponding to those measured in situ for various ankle positions. These results allowed: (1) estimation of the forces in these three ligaments in various ankle positions, (2) identification of positions where ligaments were carrying no force, and (3) identification of positions where they carry large forces. The clinical analysis reveals that the anterior talofibular ligament is sensitive to excessive plantarflexion or dorsiflexion, the calcaneofibular ligament is sensitive to excessive inversion or eversion as well as dorsiflexion or plantarflexion, and that the deltoid ligament appears to be sensitive to plantarflexion, external rotation, and eversion. The fact that all three ligaments tested demonstrated different ranges of tension supports the view that there are optimal positions for testing ankle ligament integrity. PMID- 2210532 TI - The incidence of ankle sprains in soccer. AB - This study investigated the relationship between exposure time and ankle sprains in soccer. Forty-one teams (639 players) from four male senior soccer divisions at different levels of skill (divisions I-VI) were followed prospectively for 1 year. The exposure to soccer and the number of injuries per player were higher in higher divisions, but the injury incidence, percentage of ankle injuries and incidence of ankle injuries were the same at different levels of skill. Of all injuries 17 to 20% were ankle sprains and the incidence varied between 1.7 to 2.0 ankle injuries per 1,000 hours of exposure. Since players with previous ankle problems run an increased risk of reinjury we suggest that these players receive preventive advice. PMID- 2210533 TI - Triple arthrodesis. PMID- 2210534 TI - Tarsal tunnel syndrome: review of the literature. AB - Tarsal tunnel syndrome is defined as entrapment of the posterior tibial nerve at the level of the ankle. The syndrome has been associated with traumatic inflammatory etiologies. The diagnosis is made clinically by the presence of dysesthesia in the distribution of the medial and lateral plantar nerves, a positive Tinel's sign, paresthesias with compression of the nerve at the tarsal tunnel, tenderness of the nerve along its course (Valleix Phenomenon), and sensory or motor changes. Most authors suggest surgical decompression for the treatment of tarsal tunnel syndrome. The purpose of this review is to summarize the etiologies of tarsal tunnel found in the literature, to evaluate the current role of electrodiagnosis in the diagnosis of tarsal tunnel syndrome and to examine the results of treatment modalities presented. PMID- 2210535 TI - Fasciotomy of the foot: an anatomical study with special reference to release of the calcaneal compartment. PMID- 2210536 TI - Radiologic anatomy of the painful bunionette. AB - Radiographs were studied of 91 feet in 62 patients with the diagnosis of bunionette and no prior bunionette or hallux valgus operations. Various radiologic measurements were compared to a matched control group with no bunionette symptoms or previous forefoot operations. The bunionette group had a significantly increased metatarsophalangeal 5 angle, intermetatarsal 4-5 angle, and intermetatarsal 1-2 angle compared to the control group. Bunionettes were not commonly associated with lateral bowing of the fifth metatarsal or with an increased fifth metatarsal head width. Symmetry was noted between symptomatic and opposite asymptomatic feet, with the exception of an increased intermetatarsal 4 5 angle in the symptomatic feet. PMID- 2210537 TI - Symposium of forensic sciences 'Criminalistic Traces'. May 16-20, 1988, Popowo, Poland. Proceedings. PMID- 2210538 TI - Determination of ABO antigens in fingernails using the APAAP (immunoalkaline phosphatase) technique. AB - Fingernail specimens with adherent nail-bed were taken from autopsy material with blood groups A, AB, B and O. Frozen 4-5-microns sections were submerged and floated carefully during each working step. Portions of fingernails were contaminated with blood and buccal cells, respectively. Furthermore, fingernail fragments of 8 volunteers were embedded in a biocomponent adhesive according to Grieve and Kotowski (Forensic Sci. Soc., 26 29-34) (1986) and cut by the usual microtome technique. APAAP staining is a proper method for demonstrating blood group antigens in fingernails from groove to margin. Frozen sections as well as smallest specimen embedded in a suitable adhesive are applicable for staining procedures. Using freshly prepared artificial stains, blood group constellations of red blood cells and/or buccal cells adherent on the surface of fingernails may be distinguished from the nail matrix. PMID- 2210539 TI - n-Butanol in blood as the indicator of how long a dead body lay in water. AB - n-Butanol appears in large quantities in the blood of a drowned person and a correlation exists between its quantity (concentration) and the time the body lay in water. This correlation depends on the temperature of the water but not on whether it is fresh or salt water. The time of death can be fixed within the span of 0-26 days after the event, as we have found out in our research (no longer period has been examined). PMID- 2210540 TI - Drug addiction in Poland and criminalistic traces. AB - The authors describe the most popular drugs and their substitutes being used in Poland. The paper also presents the problem of developing and examining criminalistic traces in biological and some non-organic materials. PMID- 2210541 TI - The determination of drugs and their substitutes in human hairs. AB - In recent years it has become possible to detect organic pharmaceuticals and drugs in a few milligrams of a person's hair, using modern analytical methods (RIA, GC/MS, GC), whether this person has taken narcotics and other drugs in past times. With the aid of hair analysis it is possible to examine the drug career of a drug addict for up to 1 year, and sometimes for a longer time. This is mostly of great importance in criminalistics and forensic medicine, in the criminal retrospective examination of addicts. PMID- 2210542 TI - Specific features of poisoning. PMID- 2210543 TI - Determination of the causes of fires and explosions by the analysis of biological materials. PMID- 2210544 TI - Usefulness of two methods of isoelectric focusing for the erythrocyte acid phosphatase phenotypes determination in human bloodstains. AB - The authors tried to compare the usefulness of the isoelectric focusing of EAP in bloodstains on 0.2 mm polyacrylamide gel with their method of determination of the enzyme on 1 mm polyacrylamide gel. Both methods turned out to be useful but better results were obtained on 0.2 mm gel. Isoelectric focusing on the ultra thin gel is more sensitive; it gives clear enzyme strips, takes less time (30 min) and demands about half the amount of material. PMID- 2210545 TI - Graphic test as a method for estimation of testator's psycho-physical condition. PMID- 2210546 TI - Decoding of memory traces as a function of witness' intelligence. AB - The paper deals with the problem of the effectiveness of interrogation and identification parade (recall and recognition) as a function of witnesses' Intelligence Quotient. Two experiments in photo identification form were performed to verify a hypothesis that IQ does not affect the ability to recognize a human face. The subjects whose average IQ (according to Wechsler Adult Intelligence Scale WAIS) was 65.9 (females) and 66.3 (males) obtained the same results as the subjects whose average IQ was 105.3 (females) and 99.5 (males); t1 = 13.77, p1 less than 0.001, t2 = 12.13, p2 less than 0.001, chi 2 = 0, P greater than 0.99. PMID- 2210547 TI - Polymorphism of isoenzymes in preserved muscle tissues. AB - In muscles preserved in formalin enzymes were not found to be active. In muscles treated by ethanol the ESD, GLO, GPT and PGP enzymes were active. The best results were obtained in the case of acetone treatment. The phenotypes ESD, GLO, GPT and PGP in tissues corresponded with the ones in the comparative blood samples. PMID- 2210548 TI - Evaluation of high performance liquid chromatography (HPLC), enzyme linked immunosorbent assay (ELISA) and particle concentration fluorescence immunoassay (PCFIA) methods for the screening, quantitation and pharmacokinetic study of furosemide in horses. AB - Equine plasma and urine samples were analyzed by using a high-performance liquid chromatography (HPLC), enzyme-linked immunosorbent assay (ELISA) and particle concentration fluorescence assay (PCFIA). Although ELISA and PCFIA were rapid, simple and sensitive for the screening of furosemide, they did not give reproducible quantitative results. The HPLC method, which required relatively longer analysis time, provided simple and reproducible quantitative analysis of furosemide in plasma and urine. The performance of the three methods was compared for the quantitation of furosemide in plasma obtained from thoroughbred mares dosed intravenously with furosemide (500 micrograms/kg (n = 7) and 1.0 mg/kg (n = 5)). Although the plasma furosemide profiles determined by ELISA, PCFIA and HPLC were similar, ELISA and PCFIA methods exhibited considerable variation in values. At high furosemide concentrations, the PCFIA method gave better quantitative values than ELISA. However, at trace furosemide concentrations the PCFIA method gave false positive values which were not confirmed by HPLC or ELISA. The pharmacokinetic values obtained from the HPLC data and the pharmacokinetic values obtained previously from the gas chromatographic data were comparable. The data obtained by ELISA and PCFIA were not suitable for the pharmacokinetic calculations. PMID- 2210549 TI - Wernicke's lethal encephalopathy in voluntary, total, prolonged fasting. AB - A lethal case of Wernicke's encephalopathy caused by prolonged fasting is reported; the liability of physicians is evaluated. PMID- 2210550 TI - Gas chromatographic determination of cresols in the biological fluids of a non fatal case of cresol intoxication. AB - A simple and rapid method for analysis of free and conjugated cresols in biological fluids was developed. Prior to and following freeing of the conjugated cresols by acid hydrolysis in a sealed ampoule, free cresols were extracted by Extrelut column extraction, determined by gas chromatography, and confirmed by gas chromatography-mass spectrometry. In a non-fatal case of cresol intoxication a 46-year-old male had ingested about 100 ml of a saponated cresol soap solution. The concentrations of xylenol (2,4- and/or 2,5-dimethylphenol) and p- and m cresol in the serum sample collected on admission were 15.8 micrograms/g, 43.3 micrograms/g and 73.8 micrograms/g, respectively. The total cresol concentration of 117 micrograms/g in the serum is within the range of fatal concentrations, and it is suspected therefore that the patient's recovery was due to adequate therapy alone. PMID- 2210551 TI - Deaths in women of reproductive age and relationship with menstrual cycle phase. An autopsy study of cases reported to the coroner. AB - Deaths of women of reproductive age reported to H.M. Coroner were investigated to see whether or not there was a relationship with any particular phase or phases of the menstrual cycle. The phase of the cycle at death was determined by histological examination of endometrial tissue. 257 consecutive endometrial samples were examined from females that were autopsied between 1982 and 1989. 86 were discarded for various reasons, principally autolysis and the remaining 171 were placed into four histologically distinct phases of the cycle as follows: Menstrual (days 1-5); Proliferative (days 6-15): Early secretory (days (16-19): Mid/late secretory phases combined (days 20-28). There were 46 deaths from natural causes; 44 accidental deaths; 50 suicides and 31 homicides. The results from all categories of death combined, and within their four subgroups, did not show any significant bias to any particular phase or phases of the cycle. Indeed the deaths were distributed evenly as one would expect on theoretical grounds. PMID- 2210552 TI - Stain analysis using oligonucleotide probes specific for simple repetitive DNA sequences. AB - The use of oligonucleotide fingerprinting is evaluated in practical forensic work, using both artificially and systematically produced stains as well as actual case work material. The probes (CAC5/(GTG)5 are superior because of their individualizing potential in comparatively fresh specimens with little DNA degradation, whereas (GACA)4, still produces substantial information when high molecular weight DNA is lacking. The overall limitations and the advantages of this technology are discussed in detail and compared to the classical minisatellite probes. PMID- 2210553 TI - GC polymorphism detected in human urine by isoelectric focusing and immunoblotting. AB - Genetic polymorphism of GC (vitamin D-binding protein) in human urine was revealed by isoelectric focusing and immunoblotting on thin-layer polyacrylamide gels containing 2 M urea. Urine samples from 530 unrelated Japanese from the Fukui district, being only 1-2 ml of original urine, were examined, and correct GC typing was achieved by comparison with the results of direct grouping using plasma. Six common and twelve rare phenotypes were observed. The frequencies of the genes were 0.473 for GC*1F, 0.241 for GC*1S, 0.254 for GC*2, and 0.032 for the total of six rare alleles. PMID- 2210554 TI - Traumatic rupture of intracranial vertebral artery due to hyperextension of the head: reports on three cases. AB - In three cases of fatal basal subarachnoid hemorrhage due to rupture of the normal intracranial vertebral artery, the ruptures appeared to have been caused by overstretching of the vertebral artery from traumatic hyperextension of the head. In the first case, that of a 31-year-old male pedestrian who, while intoxicated, had been hit from behind by a car, symmetrically located bilateral complete and incomplete tearing of the vertebral arteries was found. In both of the other two cases, involving women aged 37 and 51 found dead after receiving fist blows to the face while intoxicated, complete rupture of the vertebral artery was found. The blood alcohol concentrations of the three cases ranged from 1.6 to 1.7 mg/g at autopsy. PMID- 2210555 TI - [Peripheral retinectomy in proliferative vitreoretinopathy]. AB - In most cases of advanced proliferative vitreoretinopathy (PVR) relief of anterior traction can be achieved by careful dissection of the vitreous base. In more complicated cases, a peripheral, usually inferior retinectomy is necessary. We have analyzed retrospectively 51 cases of advanced PVR, in which we performed a combined vitrectomy-silicone oil procedure with peripheral retinectomy. In 90% of the cases, the retinectomy was done during a reoperation. In 24 of 51 patients (47%) the crystalline lens could be preserved until removal of the silicone oil. At the end of follow-up (more than 6 months, mean 13 months), the retina was attached in 37 of 51 cases (72.5%) Reproliferation caused redetachment in 12 of the 14 failures. Reproliferation with renewed traction on the central retina frequently required revision with extension of the retinectomy, but in most eyes anterior traction could be managed successfully by this technique. PMID- 2210556 TI - [Artificial iris diaphragm in silicone oil surgery]. AB - An artificial PMMA iris diaphragm is described, which is similar to an inferior iridectomy after Ando. The diaphragm can be implanted in aniridic eyes requiring silicone oil surgery. It successfully inhibits contact between the silicone oil bubble and the corneal endothelium. PMID- 2210557 TI - [Endogenous candida endophthalmitis. Early diagnosis and early vitrectomy improve the prognosis]. AB - Our records on endogenous Candida endophthalmitis in 13 eyes in 10 patients are presented. The diagnosis was confirmed by culture from vitreous aspirate or serologic examination. The records show that cases with immediate diagnosis and treatment by antimycotics and vitrectomy have a better prognosis than late diagnosis or treatment without vitrectomy. Only the 4 cases that were vitrectomized within 4 weeks after onset of the complaints resulted in good visual acuity (greater than 2/5). The other cases were often complicated by traction, retinal scars or choroidal proliferation. Unclear uveitis with a high risk for fungal infection in the patient's history should be evaluated for Candida infection. Every patient with candidemia needs periodic ophthalmologic examinations for endophthalmitis. Diagnosis, treatment and possible prevention of endogenous Candida endophthalmitis are discussed. PMID- 2210558 TI - [Lactoferrin and transferrin--iron-binding proteins in physiological and pathological vitreous bodies]. AB - Having demonstrated transferrin (TF) and the TF receptor in periretinal membranes, we now present results of quantitative studies of TF and lactoferrin (LF), another protein with iron-binding properties. Normal human vitreous contains 74 +/- 7 mg/l TF, but less than 50 micrograms/l LF (ELISA). The TF levels determined in vitreous aspirates from patients with proliferative intraocular diseases [traumatic proliferative vitreoretinopathy (PVR), idiopathic PVR, and proliferative diabetic retinopathy (PDR)] were higher. A statistically significant difference between the levels in the vitreous in the three types of proliferative intraocular disease and in physiological vitreous was not observed. In contrary to TF, LF could not be labeled in surgically obtained membrane specimens using immunochemistry. Apparently LF does not have the same importance for cell proliferation in proliferative intraocular diseases as is suggested for TF. PMID- 2210559 TI - [Macrophages and HLA-DR expression in proliferative vitreoretinopathy]. AB - Macrophages and macrophage-like cells have been reported as cellular components of epiretinal and vitreous membranes. The origin and function of these versatile cells in the membranes are not fully understood. In the present study we used monoclonal antibodies reacting with macrophages, HLA-DR and monocytes (OKM5) to investigate cells in 52 specimens of various human epiretinal and vitreous membranes collected by vitrectomy. The results show that more than 80% of all membranes are positive for macrophage and HLA-DR antigen. HLA-DR is considered to be expressed by the macrophages. Cells reacting with antimonocyte (OKM5) are seen sporadically only in proliferative diabetic retinopathy. These results are discussed with respect to the possible origin of the macrophages and their important role in the development and formation of epiretinal and vitreal membranes. PMID- 2210560 TI - [Monapterin and biopterin in degenerated retinas]. AB - We measured the concentrations of biopterin, neopterin and monapterin in the neuroretina of humans and different rat strains and found a relatively high amount of oxidized monapterin in these tissues. The dystrophic retinae of RCS rats revealed an inverse ratio of biopterin-to-monapterin compared to LE rats. This ratio was altered in LE rats after exposure to strong light. These results suggest that changes in pterin metabolism may correlate with retinal dystrophy. PMID- 2210561 TI - [Alternatives to steroid therapy in chronic uveitis]. AB - In a search for alternative therapeutic methods other than corticosteroids and cytostatics, the effect of a dialyzable leukocyte extract (DLE), the antimetabolite 5-fluorouracil and the immunosuppressive agent cyclosporin A in corticosteroid-resistant idiopathic uveitis was studied. When DLE was administered to 26 patients who had uveitis forms with exogenous triggering (e.g., infection), as well as forms with an autoimmune background, there was a reduction in the number and duration of recurrences and a statistically proven prolongation of the inflammation-free intervals. This was particularly true in anterior and posterior uveitis and to a lesser extent in the intermediate form. No side effects were observed. 5-Fluorouracil, injected subconjunctivally, is indicated in intermediate uveitis with marked vitreous infiltration and beginning proliferation. Corneal erosion occurs relatively often. During treatment with cyclosporin A (low dose, 5 mg/kg of body weight per day), 14 of 17 patients (9 with intermediate uveitis, 6 with retinal vasculitis, 1 with sympathetic ophthalmia, 1 with panuveitis) showed improved results; in 2 cases the findings remained stationary and only 1 case had low-grade deterioration. If one takes into consideration the fact that in this patient any therapy would have failed, the results are convincing. This is particularly true of retinal vasculitis. There is no effect in cases of central hemorrhagic chorioretinopathy. So far, there have been no serious side effects. PMID- 2210562 TI - [Retinal periphlebitis and multiple sclerosis. Incidence, cerebrospinal fluid and results of visual evoked potentials]. AB - In a retrospective study 323 patients with multiple sclerosis were screened for the incidence of retinal periphlebitis. The results of lumbar puncture and the visual evoked potentials were related to the eye disease. Retinal periphlebitis was seen in 19 patients (5.9%). Of the patients with retinal periphlebitis, 79% developed the eye pathology within the first 10 years of multiple sclerosis. The cerebrospinal fluid and visual evoked potentials were no different than the results in a control group of multiple sclerosis patients without periphlebitis. Multiple sclerosis should always be considered as one of the potential underlying diseases in retinal periphlebitis since it is found in 30% before or at the same time as the first neurological symptoms of multiple sclerosis. PMID- 2210563 TI - Acute aseptic panophthalmitis caused by a copper foreign body. AB - Enucleation was performed on a 10-year-old boy after an eye injury from the explosion of a dynamite cartridge. Amaurosis was noted 48 h after the injury upon admission to our clinic. The clinical picture of panophthalmitis comprised bulbus protrusion with limited movement and hypopion; total retinal detachment was demonstrated by ultrasonography. Intensive pain was present. A histochemical investigation was performed, showing purulent exudation in the anterior chamber, choroid, and retina. Copper stained with rubeanic acid was positive. Electrogravimetrically, the foreign body was found to be 94% copper and approximately 40 mm2 in size. PMID- 2210564 TI - [Cytology of the corneal endothelium in endothelial dystrophy]. AB - The corneal endothelium of 17 corneal buttons with endothelial dystrophy was investigated by means of vital staining and light microscopy. Each type of dystrophy was characterized by typical morphological changes in the endothelium: in Fuch's endothelial dystrophy (n = 13), subendothelial guttata formation is characteristic; in congenital hereditary endothelial dystrophy (n = 2), a high amount of multinucleated endothelial cells was found; in posterior polymorphous dystrophy (n = 2), a multilayered endothelium was the striking feature. There is a coherent endothelial cell layer in endothelial dystrophy that may indicate a disturbance in the endothelial pump function rather than a barrier defect caused by gaps between the endothelial cells. PMID- 2210565 TI - [Unusual complications after wearing hard and soft contact lenses]. AB - In a clinical long-term study over a period of 10 years with 3850 patients wearing hard and soft contact lenses, unusual reactions of the cornea and perilimbal conjunctiva have been observed in 3% of all cases. Mainly corneal abrasions, cracks, clouds and mosaics have been observed, which were analyzed as being rare contact lens complications. The causes were lack of proper maintenance of the contact lenses, such as mistakes in cleaning and disinfecting the lenses, mishandling or toxic and allergic reactions due to cleaning and disinfection solutions. Only exact ophthalmological monitoring of the anterior parts of the eye and laboratory tests on the worn lenses permit differentiation between primary eye diseases and contact lens-induced complications. PMID- 2210566 TI - [Indication for and interpretation of immunohistological studies of the conjunctiva and cornea]. AB - Various conjunctival and corneal biopsies of eyes with chronic inflammation of the outer segment (e.g., following chemical burns, chronic proliferative conjunctival alterations) were examined using monoclonal antibodies. Class II antibodies were found in both epithelial and stromal conjunctival cells, indicating that there may be some etiological significance to an autoimmune process in altered tissue. PMID- 2210567 TI - Cyanoacrylate glue in the treatment of corneal ulcerations. AB - The application of tissue adhesives to treat different corneal diseases has been used extensively in recent years. Owing to the widespread application, it has been possible to establish the advantages and disadvantages of this method of treatment. Keeping in mind the disadvantages (primarily the toxicity of cyanoacrylate glue for the corneal endothelium and lens when it comes into direct contact with these structures), the application of cyanoacrylate glue was restricted to the treatment of progressive corneal ulcerations where the risk of corneal perforation was recognized. This method of treatment was applied in 30 patients with corneal melting in dry eye associated with rheumatoid arthritis (12), trophic postherpetic ulcerations of the cornea (9), chemical corneal burns (7), neurotrophic corneal ulceration (1) and Mooren's ulcer (1). The defect healed and anterior corneal surface epithelization occurred in 73.33% of patients in contrast to the additional treatment, most commonly penetrating keratoplasty, required in the remaining patients (26.67%). PMID- 2210568 TI - [Structural differences in the structure of the ciliary muscles in eyes of primates. A histochemical and morphological study]. AB - The ciliary muscle of the primate eye was stained histochemically with enzymes used to differentiate fiber types in the skeletal muscle. Differences between the outer meridional section and the rest of the muscle were found with all enzymes. Staining for myosin-ATPase with acid and alkaline preincubation, as well as for lactate dehydrogenase (LDH), resulted in a stronger reaction in the meridional section, while the reticular and circular portions showed minor activities. In contrast, succinate dehydrogenase (SDH) revealed a stronger activity in the reticular and circular muscle cells. Ultrastructurally, the meridional muscle cells contained fewer mitochondria, but more myofibrils in the cytoplasm, while circular and reticular muscle cells showed just the opposite. Therefore, the cells of the meridional ciliary muscle section resemble in some respects the rapid type-II skeletal muscle fibers, and the circular und reticular muscle cells are comparable to the slow type-I fibers of the skeletal muscle. PMID- 2210569 TI - [Anatomy of the ciliary sulcus]. AB - The space between the posterior surface of the base of the iris and the anterior surface of the ciliary body - the ciliary sulcus - and the capsular bag are the sites for a posterior chamber lens implant after extracapsular cataract extraction. In human cadaver eyes and in eyes after cataract extraction, the exact topographical relationship of the ciliary sulcus and the surrounding tissue was analyzed. The anatomical findings and important variations are documented by light microscopy and macrophotography and the relationship to lens implantation is discussed. PMID- 2210570 TI - [Histopathological findings following cryo-coagulation of the ciliary body with a nitrogen-cooled probe]. AB - A new cryoprobe was investigated in rabbits for experimental coagulation of the ciliary body. In a one-step procedure, the cyclodestructive effect was achieved by cooling the cryoprobe down to -100 degrees C without significant lens damage. The histological investigation showed extensive necrosis of the ciliary epithelium 2 h and 2 days after the freezing damage. After 2 weeks and 2 months, fibrous atrophy of the entire segment of the ciliary body could be observed. PMID- 2210571 TI - [The thermodynamics of cyclocryocoagulation]. AB - A new cryoprobe for cryocoagulation of the ciliary body was designed, which is cooled by nitrogen and permits defined coagulation of the ciliary body over 120 degrees. The thermodynamic profile of this probe was investigated in a mathematical model and in practical measurements, defining the conditions for an optimum heat transfer. PMID- 2210572 TI - [Dynamic stereoscopy and parallactoscopy and their importance for the 3 dimensional perception of moving objects]. AB - The three-dimensional perception of moving objects plays an important role in professional and everyday tasks. Nevertheless, to date it has remained relatively unnoticed in the practice of ophthalmological and occupational medicine, although in 1984 the WHO also recommended testing dynamic vision. To determine dynamic stereoscopic visual acuity, the binocular prism rotation device was constructed and to determine dynamic parallactoscopy, the parallactoscopometer. The visual acuity found via dynamic stereoscopy decreased relatively quickly with increasing velocity (n = 103) and differed from stereoscopy determined at rest. Dynamic stereoscopy led to very precise fine spatial orientation, but it failed with average velocities; dynamic parallactoscopy had coarser visual powers, but it was relatively independent of speed and thus rendered essentially better spatial orientation possible at rapid velocities. It is possible that at slow pedestrian speed the two were equal. Under much-reduced light densities and reduced visual acuities, dynamic parallactoscopy remained intact in contrast to dynamic stereoscopy. PMID- 2210573 TI - [Luminance contrast and color contrast evoked pattern electroretinogram in normal eyes and in eyes with glaucoma]. AB - Pattern-onset ERGs obtained with color contrast (red-green, blue-yellow) and luminance contrast (green "black") square-wave-stripe patterns (spatial frequency 0.3 c/deg, 32 degree field) were studied in larger groups of normal and glaucomatous (chronic open-angle glaucoma) eyes. Colored stimuli were generated in a two-channel Maxwellian-view system using grating monochromators. In producing isoluminant lights of different colors, the peak latency of the response was used as a criterion. Luminance-contrast responses always have significantly smaller amplitude and shorter peak latency than color-contrast responses. This can be explained by the smaller number and shorter latency of the non-color-coded phasic anglion cells and by the larger number and longer latency of the color-coded tonic cells. Glaucomatous eyes respond with significantly smaller amplitudes at all contrast conditions tested; however, this response reduction is most pronounced with red-green patterns. Peak latencies are not significantly altered in glaucomatous eyes. Since red-green patterns are most appropriate in showing glaucoma damage in the pattern ERG, the largest absolute losses seem to occur among the large red-green antagonistic group of ganglion cells. PMID- 2210574 TI - [The influence of anamorphotic image formation on the visual evoked cortical potential]. AB - The correction of astigmatism by spectacle lenses involves anamorphotic image formations and produces distortion of retinal images, putting strain on the sensory part of fusion. These distortions were artificially produced by anamorphotic telescopes in a group of emmetropic volunteers. In binocular visually evoked cortical potential (VECP), a transient increase in amplitudes was recordable after application of the anamorphotic distortions. The removal of anamorphotic telescopes resulted in a distinct decrease in amplitude, followed by an overshoot increase before recompensation to pretest values occurred. The amplitude reactions observed are suggested as being an objective indicator of the cortical fusion mechanism. PMID- 2210575 TI - [Monitoring of vision development following early surgery of congenital cataracts using the Acuity-card method]. AB - The recently developed acuity card procedure provides rapid assessment of visual acuity in preverbal infants and thus offers the possibility of monitoring the visual development of infants after early surgery for congenital cataract. This report describes our experience with these acuity cards in seven patients with bilateral and seven patients with unilateral congenital cataract. The age at operation was between 1 week and 17 months; visual acuity was assessed up to an age of maximally 2.5 years. In agreement with previous reports, the development of acuity in infants with unilateral aphakia was better if surgery had occurred within the first 6 months of life than at a later time. The results of acuity assessment were generally in good agreement with the clinical signs. The advantages of the acuity cards in clinical use are that: (1) they provide an additional criterion for surgery, including cases of secondary cataract formation; (2) they allow early assessment of the success of the operation; (3) they can be used to judge occlusion therapy; (4) they have proved to be highly motivating for parents to comply conscientiously with the therapeutic measures. Thus, the acuity card procedure has proved to be extremely useful for the assessment of visual development in infants operated on for congenital cataract. PMID- 2210576 TI - [Results of scanning electron microscopy following internal laser sclerostomy]. AB - An experimental glaucoma-filtering procedure ab interno, laser sclerostomy, can be performed using the argon and Q-switched Nd:YAG laser. Compared with surgical techniques the advantages of laser sclerostomy are: minor trauma to the conjunctiva and no risk of infection. In this study 28 rabbit eyes were examined by histological techniques and by scanning electron microscopy 2 days or 4 months following laser sclerostomy. The internal fistular ostium as well as the scleral tunnel showed a relatively smooth margin. Two days after laser sclerostomy, endothelial cell damage was found in only a small area directly surrounding the internal ostium; 4 months later all of this damage was repaired. PMID- 2210577 TI - [Mechanism of ascorbic acid transport in the aqueous humor]. AB - The concentration of ascorbic acid in the aqueous humor in many species (including humans and oxen) is several times higher than the plasma concentration. The role of ascorbic acid as a protective mechanism in the intraocular tissues against light-induced damage is discussed. We have performed uptake studies using 14C-labeled ascorbic acid in cultured bovine pigmented ciliary epithelial cells in order to study the mechanisms for ascorbic acid transport from the ciliary body to the aqueous humor. We found that intracellular accumulation of ascorbic acid was Na(+)-dependent. Data from kinetic experiments suggest the presence of a co-transport system for 2 Na+ and 1 ascorbate. The oxidized form of the vitamin (dehydro-ascorbic acid, DHA) was taken up in the cell by a Na(+)-independent mechanism. Using thin-layer chromatographic assay, we found intracellularly only ascorbic acid after incubation with extracellular DHA, indicating the presence of DHA reductase activity in ciliary body epithelial cells. Thus, these cells possess two mechanisms for intracellular accumulation of ascorbic acid: (1) co-transport for 2 Na+ and 1 ascorbate and (2) a Na(+) independent DHA transport in cooperation with intracellular DHA reductase. These mechanisms could be involved in the transport of ascorbic acid from the stroma to the aqueous humor. PMID- 2210578 TI - [Aquadiassectio alia post aliam. A helpful technique in the fractionated preparation of the lens nucleus in extracapsular cataract extraction]. AB - The surgical step in separating the lens nucleus from the lens cortex is frequently the most traumatizing moment. The trick in multiple aqua dissection permits severance of the lens nucleus from the lens cortex and the lens cortex from the capsule in precisely defined planes under completely controlled conditions, retaining the advantages of the closed system. Penetration of the separating fluid front can be recognized well in advance of the red light reflex. The segregation lines are shown in the drawing in an intensified, annularly arranged red light reflex, which is realized in the concentrically stratified structure of the lens. In phacoemulsification it is thus possible to remove the inner nucleus first and separately. The posterior capsule can then be well protected by a thicker cushion of cortex. Multiple fractionated hydrodissection - aquadissection alia post aliam - is not only a good example of substantial reduction in surgical trauma, but allows good control in the bag phacoemulsification. PMID- 2210579 TI - [Alcohol embryopathy. Review and case example]. AB - Fetal alcohol syndrome is a disorder that occurs in children of alcoholic mothers and is characterized by typical craniofacial dysmorphia and retardation of mental and physical growth. Semiquantitative evaluation of the most common symptoms permits clinical classification into three stages. Although numerous hypotheses have been suggested, the pathogenetic mechanism is not yet well understood. Prevention through medical advice and counselling still remains the most successful form of therapy. A case of fetal alcohol syndrome caused by excessive maternal drinking accompanied by high nicotine consumption during pregnancy is reported. PMID- 2210580 TI - [British cattle plague--also a danger for man? Bovine spongiform encephalopathy (BSE)--scrapie disease]. PMID- 2210581 TI - [Immunological factors in extracorporeal fertilization. The role of antibodies against spermatozoa and zona pellucida antigen]. AB - Immunologic disturbances must be considered a major cause of unexplained infertility. To evaluate the influence of sperm antibodies (SPAB) and zona pellucida antibodies (ZPAB) on the pregnancy rate, we have screened patients treated by in-vitro fertilization (IVF) and embryo transfer (ET) in the Department of Obstetrics and Gynecology of the School of Medicine, Hannover, for the presence of sperm antibodies and zona pellucida antibodies in the serum, cervical mucus and uterine secretions, and also in the serum and ejaculate of the husbands. After embryo transfer the concentrations of progesterone and beta-hCG in the sera were determined to evaluate the luteal phase and to detect early pregnancy. Among 122 women 11 clinical pregnancies were achieved; 8 of these pregnant women showed negative antibody reactions, while only 3 women with significant positive reactions for SPAB or ZPAB became pregnant. Only one pregnancy occurred in 24 women with high ZPAB titers. In conclusion, determinations of SPAB- and ZPAB-titers in serum and genital secretions are highly recommended in the evaluation of infertile couples. PMID- 2210582 TI - [Immunosuppressive agents in endocrine ophthalmopathy. Clinical and experimental studies using cyclosporin and ciamexone]. PMID- 2210583 TI - [Cyclosporin level under famotidine administration. Pharmacokinetic study in 20 patients following heart transplantation]. AB - The H2-receptor blocker famotidine can be recommended for use for stress ulcer prophylaxis in patients who have undergone a heart transplantation. Its very good therapeutic effect and unproblematical pharmacokinetics with no disturbance of cyclosporine A kinetics are points that favor further use of famotidine in heart transplant patients. PMID- 2210584 TI - [Health hazards associated with flying and diving. ENT aspects]. AB - The popularity of scuba diving among the general public and the great increase in air travel are increasingly associated with health problems. In the ENT sector, such problems mainly take the form of barotrauma that can arise from changes in the volume of gases enclosed within body cavities, due to fluctuations in pressure during diving and air travel. More rarely, decompression illness can occur when the required time for decompression is ignored by a diver coming up to the surface, or when a sudden loss of pressure occurs in the cabin of a plane, leading to the liberation of nitrogen dissolved in body fluids. Pathomechanisms, symptoms and treatment of barotrauma affecting the middle and inner ear and the sinuses, together with the effects of decompression errors on the organs of hearing and balance, are described, and suggestions for their prevention given. Fitness for diving and air travel, together with diseases that render these inadvisable, are discussed. PMID- 2210585 TI - [Combination drugs in geriatrics. The need for clinical studies in this special age group]. AB - Multimorbidity frequently prompts the use of multiple drugs with the aim of treating the individual diseases simultaneously. Ingestion of a number of different drugs incurs the risk of early and more frequent side effects, as well as interactions between the various drugs. There is a tendency among patients of all age groups, intentional or unintentional not to take their medication. Among elderly patients regular compliance is a special problem. Reduction of the high consumption of drugs by the elderly is possible by therapy with combination drugs. The present paper discusses the advantages and disadvantages. PMID- 2210586 TI - [Indications for antihypertensive drug therapy. German League for the Control of Hypertension]. PMID- 2210587 TI - [The treatment of irritable colon. Efficacy and tolerance of buscopan plus, buscopan, paracetamol and placebo in ambulatory patients with irritable colon]. AB - A double-blind, randomized parallel group trial comparison involving 712 patients with irritable bowel syndrome was performed. Over a treatment period of 4 weeks hyoscine-N-butylbromide (30 mg/day p.o.) plus paracetamol (1 500 mg/day p.o.), hyoscine-N-butylbromide (30 mg/day p.o.), paracetamol (1. 500 mg/day p.o.) or placebo (3 tablets/day p.o.) were administered. Patients kept a diary and entered a daily rating of their symptoms (visual analogue scale). At the end of the four weeks 81% of the patients in the Buscopan plus group were deemed "responder" (marked or some improvement in symptoms). In the Buscopan group 76%, in the paracetamol group 72% and in the placebo group 64% of the patients were responders. The differences between the Buscopan plus group and the placebo group, and between the Buscopan group and the placebo group were statistically significant. The daily rating on the analogue scale showed a statistically significant improvement in abdominal pain intensity in the Buscopan plus group versus the placebo group and in the Buscopan plus group versus the paracetamol group. Thirty-eight patients ( = 5%, no differences between the treatment groups) experienced adverse effects, that did not require treatment. Buscopan plus and Buscopan are suitable for the treatment of the irritable bowel syndromes. PMID- 2210588 TI - ["The patient must understand the therapy". Interview by Brigitte Schalhorn]. PMID- 2210589 TI - [Hydrotalcite--a multi-functional polyadsorbent. Current aspects of the status of lattice-emulsion antacids]. PMID- 2210590 TI - [5th Congress of the German Society for Biological Psychiatry. 11-13 October 1990, Berlin. Abstracts]. PMID- 2210591 TI - [Abrupt onset and rapid deterioration in the course of congenital ornithine transcarbamylase deficiency: a case report]. AB - We report a 17-year-old female case of ornithine transcarbamylase (OTC) deficiency who died of brain edema due to hyperammonemic attack. The patient had a brother with OTC deficiency who had died of hyperammonemia at 17 years of age. She firstly had a symptom of headache, nausea, vomiting and myalgia at 14 years old and twice thereafter. On admission she had a severe disorientation and vomiting. The plasma ammonia level was 89 micrograms/dl, then increased to 400 micrograms/dl in five hours. In addition to plasma exchange, hemodialysis and then peritoneal dialysis for next 5 days, parenteral sodium benzoate and arginine were administered. Although the plasma ammonia level improved gradually, her consciousness never returned and she died of severe brain edema with uncontrollable hypotension on day 8. Histology of a necropsy liver sample showed fatty metamorphosis of hepatocytes mainly with fine lipid droplets. Electron micrograph of hepatocytes showed crystalloid inclusions in mitochondria. Significance of the clinical course and the treatment during hyperammonemic crisis was discussed. PMID- 2210592 TI - Perspectives in antiviral chemotherapy. AB - The current progress in antiviral therapy is related to our better understanding of the viral multiplication, with potential targets for specific antiviral action at each step of the multiplication cycle inside the infected cell. Amantadine and Rimantadine are anti-influenza A drugs interfering with the penetration and the release of the virus. Most of the other antiviral drugs which are clinically available have the same target in common, namely the viral DNA polymerase. This holds true for modified nucleosides such as Acycloguanosine (Acyclovir), DHPG, Adenine-Arabinoside, Azidothymidine as well as pyrophosphate derivatives such as phosphonoformic acid. Unfortunately the antiviral chemotherapy must confront 3 obstacles: 1) a possible interference with the normal cellular metabolism, leading to residual cytotoxic side effects; 2) the genetic variability of the viruses, producing drug-resistant mutants and 3) the inability of any antiviral chemotherapeutic agent known to date to eradicate latent viral infection. A new approach of the control of latent infection is suggested with anti sense oligonucleotides of hybridons. PMID- 2210593 TI - Excimer laser coronary angioplasty: American multicenter experience. AB - Second generation angioplasty devices remove rather than displace atherosclerotic plaque. For such devices to be useful they must be capable of addressing the major problems not solved by balloon catheters: difficult anatomy, abrupt reclosure, and restenosis. Laser angioplasty systems have proven difficult to adapt to treatment of coronary artery disease, because of heat generation, problems with perforation, and inflexibility of optical fibers. The AIS excimer laser coronary angioplasty system couples a 308 nm pulsed excimer laser to multifiber over-the-wire catheters of 1.3 mm, 1.6 mm, and 2.0 mm diameters. The laser's uniquely long pulse width (250 ns) allows delivery of higher energies through smaller fibers. Because the catheter system is front firing, risk of perforation is reduced. The Excimer Laser Coronary Angioplasty Registry involves six institutions investigating the AIS excimer system. This report deals with 255 lesions in the first 210 patients in the registry. The study cohort resembles a standard angioplasty population in terms of demographics, symptomatology, vessels dilated, and complications. Unlike a standard PTCA cohort, the ELCA patients had a higher prevalence of chronic total occlusions, calcified lesions, long lesions and diffuse disease. Both very distal lesions and those that had previously failed PTCA were successfully treated with ELCA. The laser was successful in 85% of cases, but adjunctive balloon angioplasty was required in the majority. There were no instances of perforation. PMID- 2210594 TI - [Percutaneous coronary excimer laser angioplasty]. AB - Available preliminary clinical studies have shown that ablation of atherosclerotic plaques can be achieved by means of pulsed excimer laser coronary angioplasty via flexible energy transmission systems. The goal of current studies using improved catheter technology is to enhance the acute success rate since, based on initial studies, it can be assumed that only about 40 to 45% of the patients can be successfully treated. The on-going investigations were carried out primarily with three different excimer laser systems which employ a wavelength of 308 nm but differing pulse widths and transmission systems. In the first American multicenter study by Litvack and Margolis a catheter system was used with a pulse width of 180 to 220 ns. The fibers have a shaft diameter of 100 microns with a conically-thickened distal end measuring 200 microns, the ablative area encompasses 35 to 45% of the total catheter tip surface. The excimer laser used in the second American multicenter study by Sanborn and Isner has a pulse width of 120 ns. This catheter is relatively unflexible due to the 200 microns fiber diameter. The ablative catheter tip area is 25 to 30%. In Tubingen a system was used with a pulse width of 60 ns. The energy is transmitted through fibers with a diameter of 100 microns. The effective ablative area in the first series of patients was about 15%, in the second series about 25 to 30%. At present, the energy density of all three systems is comparable with at least 25 to 35 mJ/mm2. Since there is currently no means for accurate assessment, the question of whether a shorter pulse width of comparable energy density is more effective than the longer pulse width, remains an open issue. The flexibility of the systems used by Margolis and in Tubingen enable ablation not only of proximal, but also arteriosclerotic plaques located in the middle-third of vessels. The flexibility and steerability, however, are inferior to balloon catheter systems. In the study carried out by Litvack and Margolis, in which more than 600 patients have been treated, and the results from 514 patients reported, there was no patient selection in the first series. The study by Sanborn and Isner included 88 patients. Due to the relatively unflexible catheter system, only those patients were treated who had proximal stenosis of the left anterior descending or right coronary artery or marginal branches of the circumflex artery without marked tortuosity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2210595 TI - Percutaneous recanalization of chronic total coronary occlusions: experience with the direct argon laser assisted angioplasty system (LASTAC). AB - The present study reports initial experience with the argon laser LASTAC system in patients with chronic coronary artery occlusion not amenable to recanalization with conventional systems. The LASTAC system conducts focused argon laser light through an optical fiber of 200 microns which is inserted through a multiple lumen balloon catheter. The balloon serves the purpose of coaxially positioning the optical fiber. The balloon catheter is advanced by means of a guidewire to about 2 mm proximal to the occlusive lesion. After advancing the optical fiber, in three times 10 to 20 Joules are applied. Thereafter, the optical fiber is withdrawn, the balloon deflated, the catheter system repositioned and the sequence repeated. The integrity of the system with respect to temperature increase, energy loss and contact with tissue is monitored with lens fluorescence. In 29 patients with angina pectoris and documented ischemia, 30 complete occlusions were treated. In 18 (60%), there was successful recanalization with conventional balloon dilation thereafter. The total success rate for the right coronary artery was 55%, for the circumflex artery 71% and for the left anterior descending artery 67%. With regard to complications, in one patient there was nontransmural myocardial infarction, in seven there were asymptomatic dissections, one patient required defibrillation. The value of the LASTAC system for recanalization of chronically occluded coronary arteries has not yet been fully delineated. However, the success rate of 60% in previously treatment-refractory patients as well as the fact that no perforations were incurred, is encouraging. Further assessment will require analysis of long-term results as well as comparison of other methods. PMID- 2210596 TI - [Spontaneous variability in ischemic episodes during everyday conditions. Role of ST-Holter monitoring in assessment of therapy]. AB - To analyze the daily spontaneous variability of ischemic ST-segment changes and to derive criteria for statistical documentation of a therapeutic antiischemic effect, in 30 patients with coronary artery disease, with the aid of Holter monitoring the frequency of episodes E1 and E2 during everyday activities without medication was registered for two consecutive 24-hour periods. The spontaneous variability of the ischemic episodes of an individual patient was defined as the frequency distribution of the respective percent changes [(E2-E1)/E1].100 = (E2/E1-1).100 from day to day. To fit the curve to a normal distribution, logarithmic transformation was performed: [formula: see text] where i designates the number of patients. The constant 0.01 serves to correct for the event of episode frequency = 0. From the standard deviation sd of this logarithmic quotient, by retransformation, the one- and two-sided confidence limits K for the percent spontaneous variability are derived from the equation K = -(10-z alpha.sd 1).100; z alpha = 1.65 or 1.96. A statistically significant therapeutic effect can be assumed if, on paired comparison of 24-hour registrations with and without treatment, the limits are exceeded. Possible aggravation by the drug must be ruled out with the one-sided confidence interval. From the standard deviation sd, the standard deviation sd/square root of n for the collective of n = 5 ... to n = 30 patients was calculated and, analogously to the individual patient, the corresponding one- and two-sided 95% confidence limits for a significant therapeutic effect are defined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210597 TI - [Treatment of symptomatic and asymptomatic myocardial ischemia using 120 mg delayed-action ISDN]. AB - Most episodes of myocardial ischemia in patients with coronary artery disease are incurred asymptomatically during everyday physical activities. While the necessity for medical treatment of angina pectoris is clearly established, the indication for treatment of asymptomatic ischemia is based on prevention of structural myocardial damage or malignant arrhythmias and on the implication of improvement in prognosis. In this regard, however, no reliable data is available. Additionally, only relatively few controlled studies have been carried out to investigate the influence of medical treatment on the ischemic episodes. Moreover, on assessment of treatment with Holter monitoring, as opposed to standardized ergometric testing, the substantial spontaneous variability of the frequency of ischemic episodes from day to day must be taken into consideration. Accordingly, in 25 patients with documented coronary artery disease, using a double-blind, randomized, placebo-controlled protocol with two periods of 48 hours of Holter monitoring each, we analyzed the effects of 120 mg isosorbide dinitrate in sustained-release form on the frequency, duration and extent as well as the circadian variation of transient myocardial ischemia during everyday physical activities and differentiated these from the spontaneous day-to-day fluctuations. During the placebo phase, 277 episodes with ST-segment depression greater than 1 mm were detected, 81% of which were asymptomatic. During treatment with 120 mg isosorbide dinitrate in sustained-release form, the number of episodes was reduced significantly (p less than 0.05) to 119 (-57%) where the decrease in symptomatic and asymptomatic episodes of 54% and 58%, respectively, was comparable (Figure 1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210599 TI - Esophageal carcinoma. PMID- 2210598 TI - [Efficacy of prophylactic nifedipine therapy during aortocoronary vein bypass interventions. Drug concentration with oral or intravenous nifedipine administration; hemodynamics and plasma catecholamines]. AB - To assess the usefulness of prophylactic nifedipine in coronary artery surgery, in this study nifedipine plasma concentrations were determined in patients, who had been given 10 mg nifedipine orally before operation. Furthermore, plasma and tissue concentrations of nifedipine were measured in patients receiving a nifedipine infusion. In this group of patients the efficacy of nifedipine, based on changes in hemodynamics and plasma catecholamines was also investigated. Patients with normal global left ventricular function (LVEDP less than 15 mm Hg, EF greater than 0.5) undergoing coronary artery bypass grafting (CABG) operations were included in this study. The preoperative antianginal therapy was continued until the time of surgery, the last beta-adrenoceptor blocker was given on the day of surgery. A standardized premedication and anesthesia (fentanyl flunitrazepan infusion) was given to all patients. Hemodynamic parameters were obtained using indwelling arterial, venous and pulmonary artery thermodilution catheters. The high-pressure-liquid-chromatography (HPLC) method was used to measure plasma catecholamines as well as plasma and tissue nifedipine concentrations. Eight patients received 10 mg nifedipine orally one hour prior to anesthetic induction. Plasma nifedipine concentration (Figure 1) showed a wide interindividual scattering at anesthetic induction (25 +/- 38 ng/ml) in this group and they decreased to low, noneffective levels during surgical stimulation (12 +/- 12 ng/ml) and aortic cannulation (8 +/- 8 ng/ml). 24 patients with a nifedipine infusion of 0.30 micron/kg/min prior to extracorporeal circulation (start: following intubation, termination: at aortic cannulation) were compared to a control group of 24 patients with respect to hemodynamics, plasma catecholamines, anesthetic requirements and need for additional vasodilator and vasopressor therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210600 TI - Squamous carcinoma of the esophagus. PMID- 2210601 TI - En bloc esophagectomy: the first 100 patients. AB - Between 1969 and 1984, 251 patients with carcinoma of the esophagus were evaluated. One hundred and eleven patients underwent en bloc esophagectomy. The technique of operation is described. Hospital mortality was 11% (12/111). Complications occurred in 49 patients. There have been no recurrences of cancer more than 3 years after operation. Absolute survival at 5 years is 55%, 29%, 15%, and 8% for W1N0, W1N1, W2N0, and W1/W2N2, respectively. En-bloc resection could be accomplished for esophageal carcinoma with an acceptable mortality and morbidity. The operation is potentially curative in a small subset of patients with unfavorable prognostic factors. PMID- 2210602 TI - Gangrene in esophageal substitutes after resection and bypass procedures for carcinoma of the esophagus. AB - In 760 resection and bypass procedures for esophageal cancer, 30 patients (3.9%) developed gangrene in the esophageal substitute. The incidence in resection cases was similar to those who were bypassed. The important factors in its development were the length and type of organ used as an esophageal substitute. Gangrene was almost exclusively seen when the upper anastomosis was in the neck; the lowest incidence occurred when stomach was used (1%), while the highest was seen with jejunum (11.3%) and colon (13.3%). PMID- 2210603 TI - Preoperative TNM classification of esophageal carcinoma by endosonography. AB - Endosonography was performed preoperatively in 111 patients with an esophageal carcinoma. The results were correlated with the histology of resected specimens employing the new (1987) TNM classification. Endosonography was accurate in assessing the depth of tumor infiltration (overall accuracy: 89%). Early carcinomas could be distinguished from advanced cancer. Extensive stenosis preventing the passage of the instrument was a limiting factor prior to the availability of a small-caliber catheter echoprobe (25% of cases). Endosonography was helpful for diagnosing lymph node metastasis, but was less accurate in defining non-metastatic enlarged lymph nodes (accuracy: 81%, sensitivity 95% and specificity 50%). The incidence of lymph node metastasis increased with the progression of tumor infiltration. Endosonography was also less accurate for diagnosing liver metastases and peritoneal dissemination because of the low depth of penetration of ultrasound. Technical improvements such as a reduction in the diameter of the instrument will further enhance the accuracy of endosonography. Moreover, ES-guided cytology may become helpful for confirming the ES diagnosis of lymph node metastasis. PMID- 2210604 TI - Preoperative staging and risk analysis in esophageal carcinoma. AB - In esophageal cancer surgery a preoperative risk analysis of the patient and staging of the tumor are necessary to reduce postoperative mortality and to identify those patients who will benefit from primary surgery. A risk analysis includes the recording of cardiac, pulmonary, renal, hepatic and cerebral functions, and defines the functional limits of the various systems. Preoperatively it is most important to assess whether the primary tumor is completely resectable or not, because only patients undergoing complete tumor resection benefit from surgery with respect to the long-term prognosis. It is necessary to undertake a classification on the basis of tumor localization and local infiltration, which today can most reliably be evaluated by endoscopic ultrasonography. Advanced tumors above the bifurcation are associated with early infiltration of the tracheobronchial system, and should therefore receive preoperative treatment with combined radiotherapy and chemotherapy. Below the bifurcation, only T4-tumors invading neighboring structures should receive this pretreatment, whereas all others can be resected primarily. PMID- 2210605 TI - Esophagogastrectomy for carcinoma in cirrhotic patients. AB - Esophagogastrectomy for carcinoma of the esophagus or cardia has been performed in 32 patients with histologically proven hepatic cirrhosis. Thirty-one esophagogastrectomies were performed through a separate abdominal and right thoracic approach in 25 patients, a left thoracoabdominal approach in five patients, and without thoracotomy in two patients. One patient had a colon interposition. Seven patients died after operation (21%) as a result of anastomotic leakage in two patients, hepatorenal in four patients and portal thrombosis in one patient. The type of procedure did not influence mortality. The most common postoperative complication was the development of ascites (68%), and when associated with hepatorenal syndrome (in four patients) there was significant mortality (p less than 0.05). Sepsis was present in the terminal stages of all nonsurvivors. A prothrombin time less than or equal to 60% of normal values was the only significant preoperative predictive factor of mortality, with none of the three patients surviving below this level (p less than 0.05). It is concluded that the presence of cirrhosis is not a contraindication to esophagogastrectomy for carcinoma when curative resection can be undertaken. Hepatic reserve is the determinant factor of operative prognosis. Operative risk is acceptable if patients are classified as Child's class A, and prothrombin time is over 60% of normal values. Operation should be delayed when acute alcoholic hepatitis is present. Intraoperative discovery of cirrhosis is not a contraindication to resection when the above criteria are met. PMID- 2210606 TI - Decreased risk of gastric stump carcinoma after partial gastrectomy supplemented with bile diversion. AB - The exact incidence of gastric stump cancer is not known. The reported incidence varies greatly, even in studies using similar methods. The aim of this study was to re-evaluate the risk of gastric stump cancer after gastric surgery for peptic ulcer in the Finnish population. A total of 285 patients (252 men and 33 women) operated on for benign peptic ulcer between 1948 and 1954 were followed-up till the end of 1984 (mean follow-up for men = 19.4 years, for women = 22.9 years). At the end of 1984, 58 patients (20%) were still alive without verified gastric cancer. One patient developed gastric cancer within five years after the operation and was excluded from the series. Nine patients (3%) were lost to follow-up. Six patients (four men and two women) of the total 285 developed gastric cancer 6, 7, 8, 21, 25 and 27 years after the operation. The risk of contracting gastric cancer in a control population (no operation) of equal size and age during a similar follow-up period was 6.71 cases for men and 0.86 cases for women (total = 7.57). The observed number (6 patients) does not differ significantly (P less than 0.5) from the expected number (7.57). This study shows that the risk of gastric cancer does not significantly increase after partial gastrectomy for benign peptic ulcer. PMID- 2210607 TI - Angioscintigraphic assessment of hemodynamic effects of penbutolol in cirrhotics with portal hypertension. A double-blind, randomized, controlled study. AB - This randomized double-blind controlled study analyzed the hemodynamic effects of penbutolol, a new levorotatory beta-blocker, using radionuclide angiography. Twenty cirrhotics with esophageal varices were randomized to two groups: 10 received 40 mg/day of penbutolol orally and the others placebo. Angioscintigraphy was performed before and after an 8-day treatment period. Three cases in the penbutolol group were lost due to software damage, hence the data of 17 patients were analyzed. The two groups were matched for age, sex, etiology of cirrhosis and hepatic function. The index of portal perfusion decreased significantly ( 29%; p = 0.018) and the hepatic artery index increased significantly (+23%; p = 0.018), while no changes were observed after placebo. The heart rate decreased significantly after penbutolol (-9%; p = 0.028), while neither penbutolol nor placebo modified the ejection fraction. In conclusion, penbutolol decreased portal perfusion index (the compensatory increase in the hepatic artery index confirmed this change) without major modification of total hepatic blood flow or systemic hemodynamics. Angioscintigraphy is reasonably accurate, reproducible, safe and can be considered suitable for routine use in the assessment of liver hemodynamics. PMID- 2210608 TI - Cisapride and cimetidine in the treatment of erosive esophagitis. AB - The efficacy of cisapride, as compared with cimetidine, in the treatment of erosive esophagitis was studied in a double-blind trial. One hundred and twenty nine patients were assigned to one of four dosage schedules: cisapride 10 mg b.i.d. (20 mg group) or q.i.d. (40 mg group), or cimetidine 400 mg b.i.d. (800 mg group) or q.i.d. (1600 mg group). Treatment lasted 8 to 12 weeks. The degree of esophagitis and the severity of diurnal and nocturnal heartburn and regurgitation were significantly (p less than 0.01) reduced in the four treatment groups. Endoscopy did not show any significant differences among the four groups, although cisapride tended to be more effective in moderate to severe esophagitis, in which cases mucosal healing (i.e. absence of erosions and ulcers) was observed in 69%, 64%, 55% and 55% of the patients treated with cisapride 40 mg, cisapride 20 mg, cimetidine 1600 mg and cimetidine 800 mg. Improvement in reflux symptoms in the two cisapride groups was not significantly different from that in the cimetidine 1600 mg group, but was better (p less than 0.05) than that in the cimetidine 800 mg patients. The severity score for all reflux symptoms had decreased by 79%, 74% (cisapride 40 mg and 20 mg), 69% and 57% (cimetidine 1600 mg and 800 mg) by the end of treatment. These results show that cisapride is at least as effective as acid-suppressing therapy in patients with reflux esophagitis, and is therefore a valuable alternative to it. PMID- 2210609 TI - Determination of the ketone body ratio in fulminant hepatic failure. AB - The ratio of acetoacetate to beta-hydroxybutyrate, the ketone body ratio, was measured in arterial blood from 28 patients with fulminant hepatic failure as an index of the hepatic energy charge. The ketone body ratio was significantly reduced in the total group of patients with fulminant hepatic failure as compared with control subjects (0.27 +/- 0.03 SE as compared with 0.48 +/- 0.03; p less than 0.001). Patients who survived had significantly less reduction of the ketone body ratio on admission than those who died (0.39 +/- 0.06, n = 10 as compared with 0.20 +/- 0.02, n = 19; p less than 0.02). In seven patients who died, in whom ketone body ratio was measured less than 12 hours before death there was a significant decrease in ketone body ratio as compared with that on admission (0.24 +/- 0.05 to 0.15 +/- 0.04; p less than 0.05). In contrast, in seven patients who survived there was no significant change in ketone body ratio when measured within 12 hours of regaining consciousness as compared with the figures on admission. Measurement of arterial ketone body ratio may give an indication of prognosis, and may be of use in testing the efficacy of treatments which aim to enhance hepatic regeneration or to remove toxic substances that may reduce the hepatic energy charge. PMID- 2210610 TI - Electromagnetic shock-wave lithotripsy of gallbladder calculi. Multicentered preliminary report on experience with 276 patients. AB - The Lithostar Working Group reports on the first 276 patients who underwent lithotripsy of biliary calculi by means of an electromagnetic Lithotriptor (Lithostar Plus from Siemens). Some 66% (183/276) and 27% (75/276) of the patients had solitary and two or three stones, respectively while 7% (18/276) had more than three gallbladder calculi. Calcified calculi were found in 11% of the patients. On an average the patients were treated in 1.6 (range 1.4-2.15) sessions; with the exception of one user the maximal energy (setting 9) was applied. The upper limit of shock waves per session was 1500-6000 (x = 2189 +/- 1058). 17% and 48% of the patients were free from calculi after 3 and 6 months, respectively. During the follow-up period 14% of the patients complained of severe biliary pain and 1.5% suffered from pancreatitis, which was controlled by conservative treatment. In three out of five patients with a transitory cholestatic jaundice endoscopic papillotomy was necessary. Four patients underwent an elective cholecystectomy. Considering the selection of the patients, the results obtained are comparable with those found in other studies. PMID- 2210611 TI - Primary Budd-Chiari syndrome: its significance for the choice of surgical management of a patent right inferior hepatic vein. AB - Budd-Chiari syndrome is still a major problem and the overall prognosis for the patients is dismal and disappointing. The case history of a patient with not only outflow obstruction of the hepatic vein but also complete obstruction of the retrohepatic inferior vena cava is presented. She had a patent right inferior hepatic vein which partially decompressed the liver via a rich network of venous collaterals. Management included an inferior vena cava to inferior vena cava shunt using a Goretex graft. The patient fared well and the postoperative course was satisfactory. The case history of this patient illustrates the importance of precise pre-operative investigations for the choice of the type of surgical management. Each patient has to be considered individually on the basis of his or her mechanical peculiarities. PMID- 2210612 TI - Clinical efficacy of famotidine in the treatment of acid-related diseases: an overview. AB - The clinical efficacy of famotidine has been clearly shown in the short- and long term treatment of a number of acid-related diseases such as duodenal and gastric ulcer as well as in the acute management of reflux esophagitis. In addition, famotidine effectively treats anastomotic ulcer and nonulcer dyspepsia. Based on a number of considerations--chemical structure, pharmacokinetics, pharmacodynamics, clinical efficacy, tolerability, and dosage regimen--famotidine represents an end-point in the development of the H2-antagonist group of anti ulcer agents. PMID- 2210613 TI - Effects of hepatic disease on the pharmacokinetics of famotidine and effects of famotidine on hepatic hemodynamics and peptic ulcer. AB - The effects of hepatic disease on the pharmacokinetics of the histamine H2 receptor antagonist famotidine were studied in seven healthy volunteers and 20 patients with chronic liver disease. The acute effects of famotidine on hepatic hemodynamics were studied in six healthy volunteers and eight patients with chronic liver disease, and its long-term effects on peptic ulcer, portal blood flow, and hepatic function were studied in 34 patients with chronic liver disease and peptic ulcer. Famotidine clearance was reduced only in patients with decompensated cirrhosis, probably because of concomitant renal impairment. Infusion of 20 mg of famotidine did not reduce hepatic or portal blood flow in healthy subjects, nor did it reduce the gradient between wedged hepatic vein pressure and free hepatic vein pressure or hepatic and portal blood flow in patients with chronic liver disease. An oral dose of 20 mg of famotidine twice daily for two months healed the peptic ulcers in 33 of 34 patients (97%) with chronic liver disease without altering portal blood flow and hepatic function. Even in patients with decompensated cirrhosis, famotidine did not change hepatic function. Thus, famotidine had no effect on hepatic hemodynamics or function in healthy subjects and patients with chronic liver disease. The drug was shown to be well tolerated and effective in the treatment of gastric and duodenal ulcer associated with chronic liver disease. PMID- 2210614 TI - In vitro insulin-like growth factor I interaction with cartilage cells derived from postnatal animals. AB - This paper reports data on the in vitro effects of insulin-like growth factor I (IGF-I) and basic fibroblast growth factor (bFGF) on the phenotypic expression of epiphyseal chondrocytes grown in serum-free (SF) culture medium. bFGF mostly stimulates chondrocyte DNA and inhibits sulfated proteoglycan synthesis and type II collagen mRNA. On the contrary, IGF-I is poorly mitogenic but strongly stimulates protein synthesis and type II collagen mRNA. In addition, IGF-I prevents the expression of type I collagen gene. Lastly, chondrocytes cultured in SF medium are able to locally produce IGF-I peptides. In conclusion, IGF-I and bFGF have opposite effects on the phenotypic expression of chondrocytes in vitro: bFGF is mostly mitogenic and IGF-I appears to be a differentiating factor. PMID- 2210615 TI - Status report on the US human growth hormone recipient follow-up study. AB - Three reported cases of Creutzfeldt-Jakob disease (CJD) in young adults who had received human growth hormone (hGH) raised concerns that pituitary-derived GH had been contaminated. Subsequently reported cases have confirmed this suspicion. The US Public Health Service is conducting an investigation to determine the extent of the problem of CJD in recipients of National Hormone Pituitary Program (NHPP) GH. In addition, other possible adverse effects of GH use including leukemia are being investigated. The design, conduct and current status of the study are the subject of this report. Interview data are now available on 5,240 of the 6,284 subjects treated by the NHPP for growth problems. Analysis is underway. PMID- 2210616 TI - Pharmacological testing of growth hormone secretion. AB - The laboratory confirmation of growth hormone (GH) deficiency (GHD) has been extensively studied. Multiple stimuli induce GH release, but insulin-induced hypoglycemia usually is considered the 'gold standard'. Seventy-five to 90% of normal children have significant increments of hGH to any single test. Complete and partial syndromes of GHD have been defined, but some patients with a clinical appearance of GHD release hGH during provocative testing. Discordant results on varied tests may occur in the same child. Sequential and simultaneous tests have been attempted with diverse time patterns; testing sequence may significantly affect data interpretation. Persistent problems with GH provocative tests remain: normal data not strictly defined throughout childhood, multiple tests with discordant results, and substantial discrepancies of immunopotency estimates with different radioimmunoassays. Some children with 'normal' hGH increments during provocative tests, despite clinical GHD, may require short-term treatment with hGH to finally establish the diagnosis. PMID- 2210617 TI - Non-conventional use of growth hormone: European experience. AB - Results from several centres in Europe using biosynthetic human growth hormone (hGH) for the promotion of growth in a variety of conditions other than classical hGH deficiency were evaluated. Significant increments in growth rates were achieved by daily administration of hGH in doses appropriate for body size without disproportionate skeletal advances in short normals, Turner syndrome, low birth weight, skeletal dysplasia, central precocious puberty (reared with gonadotrophin-releasing hormone analogue) and renal failure. PMID- 2210618 TI - Non-conventional growth hormone therapy in Turner syndrome: the United States experience. AB - Beginning in 1983, 71 girls with Turner syndrome were enrolled in a prospective, randomized study of human growth hormone (hGH), alone and in combination with oxandrolone; 4-5 patient-year data are currently available on 66 subjects. While the annual growth rate of the untreated control group (expressed as a Z score for untreated Turner girls) was -0.1 SD, the annual Turner growth rate Z scores for girls receiving hGH alone were +3.1, +2.0, +1.5 and +2.9 SD for years 1-4, respectively (hGH was given daily in year 4). mean annual Turner growth rate Z scores for subjects on combination therapy with oxandrolone were +6.6, +4.3, +3.0 and +2.7 SD for years 1-4, respectively. The mean height for the 20 subjects greater than or equal to 16 years of age is 150 cm. PMID- 2210619 TI - Multiple target antigens in pre-type I diabetes: implications for prediction. AB - The prodromal phase of type I diabetes is characterized by the presence of a series of autoantibodies reacting with distinct autoantigens [anti-insulin, anti 64 kDa, islet cell antibodies ('antiganglioside')]. Anti-insulin autoantibodies appear to be unique in that the levels of such antibodies correlate with both the rate of progression to diabetes and age at which type I diabetes develops. With a combination of assays it is now possible to predict type I diabetes, allowing the design of research trials for diabetes prevention. PMID- 2210620 TI - Induction and pathophysiology of remission of insulin-dependent diabetes mellitus during administration of ciclosporin. London Diabetes Study Group. AB - Ciclosporin-induced noninsulin-receiving remissions in insulin-dependent diabetes mellitus are associated with enhancement of beta-cell function. Patients in remission show virtually no insulin responses to parenteral glucose, contrasting with substantial responses to mixed meals, indicating effects of nonglucose nutrients and/or enteroinsular mechanisms. Remission is associated with normal insulin sensitivity; loss of insulin sensitivity can lead to relapse. The risks of the treatment call for studies with lower doses, and it is argued that a continuing search for immunomodulatory interventions that enhance and preserve the clinical remission-phase characteristics should be pursued. PMID- 2210621 TI - Third joint meeting of the European Society for Paediatric Endocrinology (ESPE) and the Lawson Wilkins Pediatric Endocrine Society (LWPES). Jerusalem, October 29 November 3, 1989. Proceedings. PMID- 2210622 TI - Chronobiology. AB - The field of chronobiology, the study of the rhythms in plants and animals, was restricted to botanists for centuries. Only recently during the last decades could research be broadened to include animals and later even human beings. Rhythms have been documented and related to the alternation of day and night and to the succession of the seasons. Nowadays, chronobiology has developed into a multidisciplinary field in which scientists are involved in basic research as well as in applied topics. This paper gives an introduction to the field, especially dealing with the aspect of rhythm development, and the way in which the different 24-hour rhythms in children become apparent. PMID- 2210623 TI - Hormone epidermal growth factor interactions in development. AB - Epidermal growth factor (EGF) is the most important member of a family of growth factors which exert their effects via a single 170,000 Mr plasma membrane receptor. Other members include transforming growth factor-alpha (TGF-alpha), amphiregulin and several viral growth factors. The receptor is widely distributed in fetal and postnatal tissues. The predominant family member in the fetus appears to be TGF-alpha. EGF production in tissues matures in the perinatal period. Activation of the receptor in the fetal and neonatal periods in rodents evokes important growth and development actions. Tissue EGF and EGF receptor concentrations are modulated by thyroid hormones, estrogen, testosterone and growth hormone, suggesting that selected growth and developmental actions of thyroid and steroid hormones may be mediated by EGF. PMID- 2210624 TI - Androgen receptor defects in patients with minimal and partial androgen resistance classified according to a model of androgen-receptor complex energy states. AB - We have characterized intracellularly the androgen-receptor (A-R) complexes formed by genital skin fibroblasts from 2 unrelated males with qualitative defects of the androgen receptor: one has a small nonhypospadic penis as part of a syndrome of mild androgen resistance; the other was born with ambiguous external genitalia. The dissociation rate constants of testosterone, methyltrienolone (MT), dihydrotestosterone (DHT) and mibolerone (MB) from normal androgen receptors were determined at various temperatures: when plotted by the method of Arrhenius, they yielded a linear hierarchy of dissociation states with energies of state IV greater than III greater than II greater than I, respectively. Relative to this hierarchy, patient A-R complexes were displaced to higher, androgen-inappropriate energies in a mutant-distinctive pattern. MB- or MT-R complexes of both patients were thermolabile; however, both up-regulated normally in response to prolonged incubation with either hormone. Apparent equilibrium affinity constants (Kd) of the DHT- and MB-R complexes formed by both patients were normal; however, the binding capacity (Bmax) for MB in 1 case was subnormal. The distinctive biochemical phenotypes of A-R complexes in these 2 patients with androgen resistance will facilitate the definition of structure function relations in the androgen receptor, a classical DNA-binding, transcription-regulating protein. PMID- 2210625 TI - Structural and functional studies of mammalian progesterone receptors. AB - During the past years there has been an improvement in our understanding of the molecular mechanism of action of the progesterone receptor (PR). This was due to the obtention of monoclonal antibodies against PR which allowed the first structural analyses and led to the cloning of the genes. PMID- 2210626 TI - Regulation of glucose transporters in diabetes. AB - It is now widely accepted that insulin stimulates glucose metabolism in its target tissues via recruitment of transporters from a large intracellular pool to the plasma membrane. Recent studies, however, suggest a two-step model for insulin action, of transporter translocation and transporter activation. Data confirming this hypothesis for the first time are presented. It is shown that insulin significantly enhances the intrinsic activity of glucose transporters in human and rat adipose cells, in physiological as well as in diabetic state. The functional activity of transporters is impaired in the diabetic state, but surprisingly, 'diabetic' transporters exhibit normal or even enhanced intrinsic activity. In both noninsulin-dependent diabetes mellitus and streptozotocin diabetic rats, insulin resistance is associated with 50% transporter depletion in the intracellular pool, thus leading to a decreased number of transporters appearing in the plasma membrane in response to insulin. It is concluded that impaired glucose transport in diabetes is secondary (1) to intracellular transporter depletion, and (2) to the presence of inhibitory factors interfering with the full expression of glucose transporters at the plasma membrane, thus contributing to postreceptor insulin resistance. PMID- 2210627 TI - Circadian and pulsatile TSH secretion under physiological and pathophysiological conditions. AB - In addition to the well known circadian rhythm of TSH secretion a pulsatile pattern of release has been shown. Analysis of the pulsatile release by different computer-assisted methods revealed systematic differences in the number and distribution of TSH pulses. Using the same approximation of false positive pulses (less than 1%) in any of the 21 healthy male volunteers tested a lower number of pulses was found by the Pulsar method (mean 5.1 +/- 2.0/24 h) than by the Cluster (10.6 +/- 1.8) or the DESADE program (13.6 +/- 4.6). The results of the Cluster and Desade analysis fit well to that of Fourier transformation which revealed a dominant frequency at 160 min. In addition dominant frequencies in comparison to a noise series were found at 24 h and at 33 min. Analysis of the data in 8 h segments between 2000 and 0400 h, 0400 and 1200 h and 1200 and 2000 h by Desade and cluster revealed that app. 50% of pulses occurred between 2000 and 0400 h, suggesting an important role of pulsatile TSH release in the generation of the circadian TSH rhythm. In 3 patients with TSH-induced hyperthyroidism the circadian and pulsatile pattern of TSH secretion was similar to that in healthy controls. In contrast, in a patient with a TSH producing pituitary tumor the circadian variation of TSH secretion was abolished. Patients with a non-toxic goitre revealed a significantly lower mean TSH serum level as the control group of healthy subjects. The number of TSH pulses was slightly but significantly lower when analyzed by the DESADE program but not when analyzed with any other method. PMID- 2210628 TI - Thyrotropin (TSH) action on thyroid hormone deiodination and secretion: one aspect of thyrotropin regulation of thyroid cell biology. AB - TSH, the major signalling factor for the thyroid follicles, controls thyrocyte function in concert with other modulators of cell growth, differentiation and structural organization of the follicular-endothelial network. Most of the TSH effects are mediated by TSH binding to the TSH receptor which stimulates adenylate cyclase catalyzed cAMP production. TSH is involved in the regulation of thyroidal uptake of small molecules and nutrients, intracellular transport of thyrocyte specific proteins, and in most of the steps of thyroid hormone synthesis, storage and release. These cellular events require the fine tuned regulation of metabolic reactions, morphological differentiation and cell proliferation. Thyrocytes also express a highly active Type I iodothyronine 5' deiodinase which is controlled by TSH stimulated cAMP production. The thyrocyte specific 5' deiodinase isozyme has marked influence on the amount of T3 secreted by the thyroid. This 5' deiodinase isozyme shows most of the characteristics of the type I 5' deiodinase found in liver and kidney and is also blocked by PTU, other 5' deiodinase inhibitors, and iodinated X-ray contrast agents such as iopanoic acid, which are occasionally used in thyrotoxicosis to inhibit thyroidal T3-production by this enzyme. In contrast to the liver and kidney type I 5' deiodinase T4 and T3 are not able to induce this enzyme in thyrocytes. However, TSH stimulated cAMP production increases the thyroidal isozyme activity in contrast to the liver and kidney enzyme. This review summarizes the data on the various experimental models used up to date to characterize the thyroidal type I 5' deiodinase in various species including man. PMID- 2210629 TI - Structural analysis of the TSH receptor. PMID- 2210630 TI - Morphological changes induced by prolonged TSH stimulation or starvation in the rat thyroid cell line FRTL. AB - Subconfluent FRTL cells were examined in the electron microscope after the following treatments: i) continuous TSH stimulation; ii) starvation from TSH for 3 or 7 days; iii) seven days of TSH deprivation followed by two days of TSH stimulation. The organelle complement of cells grown in the presence of TSH appeared to be consistent with their secretory properties. Rough endoplasmic reticulum (RER), in the form of round vesicles, and Golgi apparatus, were quite prominent. Cells were not properly polarized. Their dorsal surface was covered with microvilli and occasional pseudopods. After TSH withdrawal the cells flattened on the dish, lost most of their plasma membrane specializations and reorganized actin stress fibers. RER shape was modified from round vesicles to flat cisternae which thereafter almost completely disappeared. The Golgi apparatus did not seem to be modified. Autophagic vacuoles became more prominent. All the modifications were fully reversed after TSH replacement indicating an hormonal regulation in the amount and morphology of some organelle, in particular of the RER. PMID- 2210631 TI - TSH action on iodination in FRTL-5 cells. AB - This study shows that the Fisher rat thyroid cell line (FRTL-5) can iodinate thyroglobulin (Tg) in an selective way. The Tg-iodination is TSH dependent and shows a optimum at 10-100 microU TSH/ml. Intracellularly, Tg and various other non Tg-related proteins are iodinated in a TSH dependent fashion. Tg added to the medium is specifically iodinated, this occurs already in microgram amounts, in contrast to many other proteins present in the medium. Only albumin, present in mg amounts is clearly iodinated in a lower degree than Tg. Albumin iodination is not clearly dependent of TSH. Since catalase added to the medium prevents the iodination of albumin but not of newly synthesized Tg we suggest that intracellular iodination must exist. PMID- 2210632 TI - Thyroid growth--an example of modulation of cell function. PMID- 2210633 TI - Transcriptional regulation of the murine TSH subunit genes. AB - These studies have demonstrated that the murine TSH subunit genes are sensitively regulated by thyroid hormone. The T3 receptor complex interacts with both the TSH beta and alpha-subunit gene either in or near the 5' flanking region in close proximity to the transcriptional start sites. This interaction interrupts transcription from the start sites, thus decreasing transcription of the two genes. As a result steady state mRNA levels of both TSH beta and alpha-subunit genes are decreased in the cytoplasm of thyrotropic cells. This series of interactions explains most of the effects of T3 on TSH biosynthesis. PMID- 2210634 TI - Function, proliferation and differentiation of the dog and human thyrocyte. AB - The control of the function, proliferation and differentiation of the dog and human thyrocytes are reviewed. It is shown how this study led by serendipity to the discovery of new receptors, a new modulating intracellular protein (calcyphosin) and of endemic selenium deficiency in Africa. PMID- 2210635 TI - TSH and thyroid cancer. PMID- 2210636 TI - Biliary cholesterol transport and precipitation: introduction and overview of conference. AB - Cholesterol is secreted into bile as cholesterol-phospholipid vesicles. The cholesterol and phospholipid are subsequently exposed to the bile salts contained in the bile, which leads to the process of micellation. Two situations may arise depending on whether there is enough bile salt in proportion to cholesterol to complete this "maturation" process. If the cholesterol saturation is low, at equilibrium the bile salts will have completely micellized the vesicles. On the other hand, if bile is saturated with cholesterol, the micellation process is incomplete and vesicles and micelles will be present at equilibrium. The residual vesicle in this latter situation may have a higher cholesterol/phospholipid ratio because of the greater propensity of phospholipid to be micellized. This situation may result in cholesterol nucleation. The mechanism of nucleation from vesicles and the possible role of nucleating and antinucleating proteins in this process have been discussed. PMID- 2210637 TI - Detection of vesicles in native and model biles by morphological and other structural techniques: applications and limitations. AB - Detection and characterization of vesicles in native and model biles can be achieved by both imaging and nonimaging methods. Imaging methods provide more directly interpretable information, but sample preparation problems, particularly for application of electron microscopy, are a source of serious concern. Several nonimaging methods have also been used to advantage in the study of vesicles. These methods all share the disadvantage of being model dependent, thus making data analysis indirect and inferential; this is in addition to constraints unique to each of the several nonimaging methods. It is suggested that to achieve optimal accuracy in vesicle studies, a combination of different structural methods should be used where possible. PMID- 2210638 TI - Principles of laser light-scattering spectroscopy: applications to the physicochemical study of model and native biles. AB - We present a nonmathematical treatment of the theoretical and experimental aspects of modern laser light-scattering techniques. We also describe the design of a "home-built" laser light-scattering apparatus used in the authors' laboratory for the physicochemical study of model and native biles. These powerful techniques provide nonperturbing measurements of the sizes, polydispersities and, in suitable cases, concentrations and shapes of simple micelles, mixed micelles, vesicles and large proteins in bile. the sizes of these aggregates (10 to 2,000 A) fall within limits resolvable by laser light and are conventionally expressed as mean hydrodynamic radii, Rh. Static light-scattering measurements of biliary lipid aggregates provide molecular weights and important information concerning particle shape, whereas quasielastic (also referred to as dynamic) light-scattering measurements assess particle sizes and polydispersities. Under favorable circumstances, quasielastic light scattering allows simultaneous determinations of sizes and concentrations of coexisting particle populations. The use of laser light-scattering technology in solving the solution properties and the physicochemical structures of model and native biles is detailed. In view of the extraordinarily diverse backgrounds of researchers in the gallstone field (e.g., internists, surgeons, biochemists, physicists), we believe that the present article (which relies heavily on graphical representations) will afford a better understanding of the usefulness and limitations of laser light-scattering techniques, particularly in their applications to the study of bile. PMID- 2210639 TI - Gel filtration and quasielastic light scattering studies of human bile. AB - Analyses of cholesterol carriers in the extremely variable biliary samples were performed by chromatography under standard conditions. Sephacryl columns were eluted with buffer containing 10 mmol/L sodium cholate, 150 mmol/L sodium chloride, 50 mmol/L Tris(hydroxymethyl)aminomethane-hydrochloride, pH 8.0, and 1.5 mmol/L ethylenediaminetetraacetate. Moderate changes in temperature, flow rate or sample size produced only minor differences in the results. Increments in bile salt concentration in the elution buffer caused progressive disappearance of vesicles and a rise in their cholesterol/phospholipid ratio. Using the standard chromatographic technique, analyses of the same bile gave reproducible results, and comparisons among various biles were possible. Quantitative light scattering measurements of bile showed that the amount of vesicular cholesterol in whole unprocessed bile was similar to that measured by Sephacryl chromatography. Analyses of human gallbladder biles using a high-resolution Sephacryl column showed four cholesterol-containing peaks: vesicles, lamellae, mixed micelles and an undefined carrier. This long chromatographic column separated the lamellar from the micellar peaks (which had merged on the short column). Phospholipid lamellae solubilized most of the biliary cholesterol. These findings were confirmed by ultracentrifugation of bile. PMID- 2210640 TI - Separation and quantitation of cholesterol carriers in native bile by ultracentrifugation. AB - The vesicular and micellar carriers of biliary cholesterol were isolated and quantitated from native bile by a simple and short isopyknic ultracentrifugal method. The method was designed to decrease the potential pitfalls of classic ultracentrifugation: osmotic effects of the centrifugation media and hydrostatic pressure effects generated in the centrifuge tube. This was accomplished by using metrizamide as an inert centrifugation medium for isopyknic separation and a vertical rotor. The buoyant density of vesicles isolated from human native bile varied between 1.010 and 1.030 gm/ml, as determined in preformed bile-metrizamide density gradients after 285 min of centrifugation. When 16% metrizamide was directly dissolved in bile, its density increased to 1.060 gm/ml. After 120 min of centrifugation, it was found that more than 95% of total vesicular cholesterol floated at the top of the centrifuge tube. This fraction appeared as one or two white opalescent bands. The present ultracentrifugal method was validated by gel filtration chromatography. It was found that more than 95% of vesicular cholesterol migrated to the top 0.4 ml of the centrifuge tube after the short-run centrifugation. Approximately 5% of total biliary cholesterol present in the vesicular fractions was in fact solubilized in mixed micelles as assessed by gel filtration chromatography. Although the proportion of vesicles and micelles estimated with the present ultracentrifugal method is in the range reported by other authors using the more common chromatographic method, we believe that our method has two major advantages. First, it eliminates the dilutional effect of buffers necessary for gel filtration chromatography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210641 TI - Secretion of biliary lipids from the hepatocyte. AB - A significant amount of biliary cholesterol is carried in unilamellar phospholipid (lecithin) vesicles, in both supersaturated human hepatic bile and unsaturated rat bile. This fact supports the concept that biliary cholesterol is normally secreted in phospholipid vesicles from the hepatocyte into the canaliculus. The fundamental aspects of biliary lipid secretion relate first to the quantitative determinants of hepatocytic cholesterol secretion into the bile and, second, to the cell biology of this process. There is a tight curvilinear coupling between the rates of bile acids and biliary lipid secretion in all animal species. The hydrophobicity of the bile acid pool may modify this cosecretory mechanism in that more hydrophobic bile acids recruit more phospholipid and cholesterol per mole of bile acid secreted into the bile. The quantitative significance of this effect, however, is relatively minor. In contrast, intrahepatic determinants, such as the rates of hepatic cholesterol esterification and very low density lipoprotein production modulated by dietary factors, may markedly change the amount of cholesterol carried in vesicles into the bile. Recent studies provide strong evidence to support the concept that biliary cholesterol output is also modulated by the amount of free cholesterol available in specific regions of the endoplasmic reticulum for recruitment by the bile acid cosecretory mechanism. The origin of biliary lipids is in the smooth endoplasmic reticulum membranes. The intracellular transport and the canalicular secretory mechanism of the precursor of biliary lipid vesicles is mostly unknown. Two theories related to the cell biology of biliary lipid secretion are discussed in this article, the fusion-budding model and the exocytotic model. PMID- 2210642 TI - Physical chemistry of biliary lipids during bile formation. AB - Present concepts suggest that the canalicular secretion of bile salts is monomeric, which in turn drives the hepatic secretion of lecithin and cholesterol presumably as unilamellar vesicles into bile. As biliary lipids are concentrated within the biliary tree and gallbladder, bile salts structurally alter lecithin cholesterol vesicles to form a variety of metastable aggregates whose structures and phase transformations are predicted by phase equilibria considerations. These structural transformations ultimately result in the dispersion of biliary lipids as thermodynamically stable micelles or micelles plus thermodynamically unstable vesicles in common duct and gallbladder biles. The experiments reviewed herein represent experimental simulations of these processes. We used pure aqueous lipid systems to model the putative stages of biliary lipid aggregation on the basis of interactions of small unilamellar vesicles of lecithin-cholesterol with bile salts as the latter's concentrations were varied from below to well above the critical micellar concentration. With submicellar bile salt concentrations likely to be found within hepatocytes, vesicle structures are not appreciably altered. However, perimicellar bile salt concentrations possibly occurring in canaliculi and bile ductules induce the formation of a hexagonal rodlike phase. On further increases in bile salt concentration, the hexagonal rods (formed from lecithin rich and cholesterol-poor vesicles) are dissolved into mixed micelles as bile salt concentrations exceed their critical micellar concentrations. In slightly cholesterol-"supersaturated" biles, the rapid dissolution of this intermediate phase results in the formation of cholesterol-supersaturated mixed micelles that, in time, give rise to a new population of cholesterol-rich vesicles that coexist with saturated micelles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210643 TI - Stability of mixed micellar systems made by solubilizing phosphatidylcholine cholesterol vesicles by bile salts. AB - Complete solubilization of phosphatidylcholine and cholesterol by bile salts in the form of stable mixed micelles requires that the effective ratio of bile salt/lipids in the mixed micelles (Re = ([bile salt] - critical micellar concentration)/([phosphatidylcholine] + [cholesterol]) will exceed a critical value. This equilibrium solubilizing ratio is an increasing function of the cholesterol/phosphatidylcholine ratio. In contrast, the concentration of sodium cholate required for solubilization of vesicles made of phosphatidylcholine and cholesterol does not increase by increasing the cholesterol/phosphatidylcholine ratio. Consequently, the latter solubilization procedure yields metastable mixed micelles whenever the cholate concentration is higher than that required for vesicle solubilization but lower than that needed for establishing a micellar equilibrium. These metastable mixed micelles undergo partial revesiculation to form cholesterol-rich vesicles that subsequently aggregate. Cholesterol crystallization appears to occur through its reorganization within these aggregated vesicles. The overall rate of the above series of processes increases sharply with the total lipid concentration and with the cholesterol/phosphatidylcholine ratio. The dependence of the rate on the effective ratio of bile salts/lipids is very complex: at any given ratio of cholesterol/phosphatidylcholine within the range of 0.3 to 0.5, increasing the cholesterol/phosphatidylcholine ratio requires higher cholate concentrations for the formation of stable mixed micelles (higher equilibrium solubilizing ratio). On the other hand, the metastable mixed micellar larsystems are long-lived whenever the effective ratio of cholate/lipids is lower than a critical value.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210644 TI - Nucleation of cholesterol crystals in native bile. AB - Any substance capable of ultimately forming itself into a solid crystal must undergo an initial step of forming crystal nuclei. The nucleation step in crystallization for all such systems has been a difficult process to describe. Even the definition of what constitutes a "nucleus" remains elusive because one is dealing with a conceptual construct that is found only in the submicroscopic domain and therefore is inaccessible to direct measurement. Based on these considerations, the so-called nucleation time assay can at best only be taken as an empirical parameter. Nucleation (operationally defined) and growth of cholesterol monohydrate crystals in both model and native biles occurs rapidly after aggregation of supersaturated vesicles. Cholesterol made available for crystal growth also originates from the vesicular pathway and not directly from biliary micelles. The exact mechanism(s) governing this linked "precursor product" relationship remains undefined. PMID- 2210645 TI - Bile acid secretion, bile flow and biliary lipid secretion in humans. AB - The transport of bile acids through the hepatocyte and the effect of this flux of molecules on bile flow, biliary lipid secretion and bile acid biosynthesis are reviewed. Efficient hepatic clearance of bile acids involves several active systems and passive uptake. Formation of coenzyme A derivatives prevents reflux of lipophilic dihydroxy bile acids. Biotransformation of bile acids during hepatocyte transport involves both type I and type II biotransformations. The major type II biotransformation is reamidation of unconjugated bile acids, but sulfation and glucuronidation also occur. The only major type I biotransformation is oxidoreduction, which converts iso- or 3 oxo bile acids to the preferred 3 alpha-hydroxy form and 7 oxo bile acids to their corresponding 7 alpha-hydroxy derivatives. Secretion of bile acids into the canaliculus is concentrative and induces osmotic flow of plasma water and solutes across the paracellular junctions between the space of Disse and the canaliculus. Bile flow in man is characterized by its low volume and by a paucity of bile acid-independent flow when compared with that of other mammals. Bile acid secretion also induces biliary lipid secretion, but some lipid secretion appears to be bile acid independent. The lipid vesicles secreted in human bile have a much higher cholesterol/phospholipid ratio than those of other mammals. During flow down the biliary tree, vesicles are solubilized by bile acid micelles, and Ca++ ions are complexed by bile acid monomers and micelles. However, the biochemical mechanisms and factors regulating biliary lipid secretion in man are poorly understood. PMID- 2210646 TI - Bile sampling, processing and analysis in clinical studies. AB - Obtaining a proper bile sample for investigative purposes is of utmost importance to obtain valid results. Bile can be collected by direct aspiration of the gallbladder, by duodenal intubation or by T-tube drainage. The optimal method of collection depends on the investigative question, as well as on the resources available to the investigator. The procedures for obtaining, processing and analyzing human bile (gallbladder and hepatic) are summarized, pointing out the disadvantages and pitfalls that may occur. PMID- 2210647 TI - Gallbladder mucin as a pronucleating agent for cholesterol monohydrate crystals in bile. AB - Mucin is a densely glycosylated macromolecule secreted by the gallbladder epithelium as the principal constituent of gallbladder mucus. Hypersecretion of gallbladder mucus occurs in response to a lithogenic diet in experimental animals, and mucus accumulates as a viscous gel within the gallbladder lumen before gallstone formation. In both animals and man, the initial stage of cholesterol gallstone formation, the nucleation of cholesterol monohydrate crystals, occurs within the mucus gel. Inhibition of mucus secretion with aspirin prevents gallstone formation in the cholesterol-fed prairie dog, indicating the importance of mucus in gallstone formation. Mucin contains domains that bind cholesterol and lecithin transported as vesicles in supersaturated bile. Furthermore, mucin accelerates the nucleation of cholesterol crystals in both supersaturated model and native biles. Binding of cholesterol-enriched vesicles to hydrophobic domains on the mucin protein core appears to be critical for the acceleration of cholesterol crystal nucleation by mucin. Further study of the structure and function of gallbladder mucin should help to elucidate the pathogenesis of cholesterol cholelithiasis. PMID- 2210648 TI - Nonmucous glycoproteins as pronucleating agents. AB - Cholesterol crystallization-promoting factors probably play an important role in the pathogenesis of gallstone disease. We have isolated one of the factors involved by using lectin-affinity chromatography. A potent promoting activity binds to concanavalin A-Sepharose. The activity is heat labile and sensitive to digestion by glycosidase but remarkably insensitive to proteases. The concanavalin A-binding pronucleator affects cholesterol solubilization in model bile in two ways. It induces a shift of cholesterol and phospholipid from the micellar to the vesicular phase but also interacts directly with cholesterol phospholipid vesicles. The concanavalin A-binding protein fraction contains at least two different promoting factors with gel permeation molecular weights of about 150 kD and 5 kD, respectively. The higher molecular weight activity could be assigned to a protein with an apparent molecular weight of 130 kD. Concanavalin A-binding-promoting activity was present in bile from both patients with and without stones, indicating that it is a normal constituent of bile. However, the activity was strongly increased in bile from patients with multiple cholesterol gallstones, suggesting that it could play a key role in gallstone formation in these patients. PMID- 2210649 TI - Crystal growth-inhibiting proteins in bile. AB - The idea that biliary proteins somehow inhibit nucleation/crystal growth of cholesterol crystals in supersaturated human biles is not new, and some supportive, albeit preliminary, evidence has already been provided for this. Progress in purification of biliary effector proteins has been slow and hindered by the lack of a sensitive and convenient assay method. The formidable problems of removing large amounts of both mucin and lipids from the samples before isolation of biliary proteins has constituted another major obstacle. Recently, the combination of a newly developed nucleation and crystal growth assay and the systematic use of lectin affinity chromatography has enabled rapid progress to be made. With these approaches, glycoprotein fractions containing primarily inhibiting activity and other fractions containing primarily promoting activity have been isolated from normal human biles. Thus these opposing activities can coexist and influence a balance of effects potentially defining the presence of health or disease. The most recent studies have led to the isolation of a single glycoprotein having an extremely potent crystal growth-inhibiting activity. PMID- 2210650 TI - Pathogenesis of biliary sludge. AB - The increasing application of ultrasonography in biliary tract disease had led to more frequent recognition of an old disorder--"biliary sludge." Sludge is detected on ultrasound as low-amplitude echoes without acoustic shadowing. It layers in the most dependent part of the gallbladder and shifts with positioning. Particulate matter in bile, such as cholesterol monohydrate crystals, has been shown to be echogenic. Agglomeration of these crystals in biles with high mucus content accounts for the layering and the characteristic appearance of the movement of sludge with alteration in patient position. Within the gallbladder, the stability of the vesicular form of cholesterol and protein-lipid interactions are important determinants of cholesterol precipitation. In mixed and pigment gallstones, the equilibrium between ionized and unionized calcium and the hydrolysis of conjugated bilirubin are also important factors. Although the risk factors contributing to the formation of gallbladder sludge have not been critically examined, it is now known that in some instances sludge can produce biliary pain and can be associated with acalculous cholecystitis, recurrent pancreatitis and, ultimately, the formation of gallstones. A better appreciation of the pathogenesis of sludge formation can help in the understanding of the genesis of gallstones and also perhaps in understanding other documented but poorly understood biliary and pancreatic disorders. PMID- 2210651 TI - Biliary calcium and gallstone formation. AB - The purpose of this paper is to present a brief overview of the current status of the field of biliary calcium and the role of calcium in the formation and maturation of gallstones. The study of free Ca+(+) ions in bile by electrochemical potentiometric measurements using Ca+(+)-selective ion-exchange electrodes is a relatively new field, but much progress has been made in the past few years. Using this powerful analytical tool, new concepts and findings have arisen in almost every aspect of biliary calcium. Although the current symposium is targeted primarily toward cholesterol gallstones, there are several areas in which understanding of biliary calcium may significantly contribute to a better understanding of the pathogenesis of cholesterol, as well as "pigment" (calcium salt), gallstones. Five broad areas are considered in relation to biliary calcium: (a) physiology (calcium entry into bile), (b) biophysics (the regulation of biliary free [Ca+(+)] as related to Gibbs-Donnan equilibria, (c) physical chemistry (the physicochemical state of calcium in bile, (d) thermodynamics (calcium solubility in bile), and (e) kinetics (pronucleating and antinucleating factors and metastable states). With more specific reference to cholesterol stones, consideration is also made of (a) the calcium salt "seed" hypothesis in cholesterol stone pathogenesis; (b) the interactions of Ca+(+) with phospholipid cholesterol vesicles, with consideration of possible structural requirements and (c) thermodynamic and kinetic factors as related to peripheral or "eggshell" calcification of existing cholesterol stones. PMID- 2210652 TI - Unconjugated bilirubin and cholesterol gallstone formation. AB - Cholesterol gallstones usually have small amounts of pigment at their centers and often have diffuse pigmentation or pigmented layers alternating with cholesterol layers and/or pigmented rims associated with calcium carbonate (eggshell calcification). The pigments are primarily monomeric calcium salts of unconjugated bilirubin anions and/or an insoluble, black, network polymer of tetrapyrroles. Bilirubin presumably can precipitate only if bile is supersaturated with calcium bilirubinates. Among various in vitro model systems, the aqueous solubilities and pK'a values for unconjugated bilirubin differ greatly. It is therefore not known whether normal bile is saturated with unconjugated bilirubin. However, all systems indicate that unconjugated bilirubin is solubilized by binding to bile salt monomers and oligomers, as well as micelles; marked metastable supersaturation of unconjugated bilirubin can occur in the presence of bile salt micelles, and both pK'a values of unconjugated bilirubin are greater than 6.0, probably because of internal hydrogen-bonding of the--COOH groups. Lecithin decreases equilibrium solubilization of unconjugated bilirubin crystals but enhances metastable supersaturation of unconjugated bilirubin. Calcium ions form insoluble salts with unconjugated bilirubin monoanions and dianions but soluble complexes with bilirubin conjugates. The solubility products of the calcium bilirubinate salts suggest that normal hepatic bile is not saturated with CaB or Ca(HB)2 but that gallbladder bile may be supersaturated with Ca(HB)2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210653 TI - Current concepts of cholesterol transport and crystal formation in human bile. AB - The presence of vesicles in human bile probably accounts almost entirely for the frequently observed, but hitherto unexplained, phenomenon of metastable cholesterol supersaturation. This, in turn, largely explains the prolonged stability of cholesterol solubilized in supersaturated human bile. Under certain overall compositional conditions for a supersaturated native bile, the vesicular phase in its contribution to total cholesterol transport also becomes supersaturated in cholesterol. Because of this, the vesicles also become unstable, leading to formation of cholesterol crystals. A simple but common example of one factor affecting composition in this way is concentration of total solutes, especially the biliary lipids. Conversely, dilution of bile (e.g., hepatic bile) markedly reduces the cholesterol saturation level in biliary vesicles. The result is that such vesicles become much more stable. Under these conditions, cholesterol crystal formation becomes unlikely and rarely, if ever, occurs. PMID- 2210654 TI - Structural studies of the lipid components of bile. AB - The lipid-rich molecular aggregates responsible for the transport of cholesterol in bile include mixed micelles and bilayer vesicles. In this review, the molecular conformations of the individual lipid components of biliary micelles and vesicles (phospholipids, bile salts and cholesterol) obtained by high resolution x-ray crystallographical analysis are described. The key conformational/packing features relevant to lipid organization, molecular interactions and cholesterol solubility in bile are discussed. The structure of cholesterol monohydrate, the major component in cholesterol gallstones, is described and problems relevant to cholesterol crystal nucleation/growth processes are briefly discussed. PMID- 2210655 TI - Quasielastic light scattering studies of aqueous biliary lipid systems and native bile. AB - During the past 15 yr, the technique of quasielastic light scattering has been used by a number of laboratories to systematically investigate the aggregative behavior of model bile systems and more recently to characterize particles present in native bile. Quasielastic light scattering investigations of aqueous bile salt solutions have indicated important similarities and differences between the various bile salt species and have led to a quantitative model for the formation of globular and rodlike micelles, based on Small and Ekwall's primary secondary micelle hypothesis. Studies of aqueous bile salt-lecithin systems have indicated three important aggregation regimens dependent on the lecithin/bile salt molar ratio and total solute concentration. Region I of the phase diagram, which includes the lecithin/bile salt and total solute concentration values found in most mammalian biles, corresponds to a population of "simple" bile salt micelles coexisting in equilibrium with a population of mixed bile salt-lecithin micelles. Region II contains only mixed micelles, whose apparent size and shape vary with lecithin/bile salt and total solute concentration in a manner consistent with a "mixed disc" model. In this model, bile salts not only coat the perimeter of the disc (as proposed in Small's original model) but are also incorporated within the lecithin bilayer, possibly as hydrogen-bonded dimers. Finally, in region III, where total solute concentration values are typically less than the critical micelle concentration of the pure bile salt, the systems contain mixed vesicles (spherical bilayer shells) whose size (approximately 130 to 500A) depends on lecithin/bile salt and total solute concentration in accordance with a simple partition equilibrium that determines the composition of the mixed vesicle bilayer.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210656 TI - Equilibrium dialysis studies on aqueous taurocholate-lecithin solutions: further validation of the method. AB - Since the 1980 publication by Mazer, Benedek and Carey on the concept of the simple micelle-mixed micelle coexistence phenomenon in the bile salt-lecithin systems, it became apparent that a reliable method was needed for measuring the coexisting species concentrations. We recently published a method based on membrane dialysis equilibrium, and the purpose of this report is to review and to validate this previous work. In the present studies, two dialysis membranes with molecular weight cut-off of 8,000 and 12,000 to 14,000 Da, respectively, and two sets of solution volume conditions were investigated with the taurocholate lecithin system. Coexistence data were obtained over a wide range of lecithin concentrations and the results were found to be in good agreement with those from the previous studies. The bile salt/lecithin molar ratios for the mixed micelles were also deduced from the data. The principal conclusion of this study is that although there is a moderate amount of variability (10% to 15%), the method is both satisfactory and useful in studying bile salt-lecithin equilibria and dynamics. PMID- 2210657 TI - Phosphatidylcholine vesicles: structure and formation. AB - Phosphatidylcholines and certain other phospholipids, as pure substances and as mixtures, can be dispersed in aqueous media to form unilamellar vesicles. The process by which these vesicles form in most instances depends on the bending and subsequent closure of an initially flat disc micelle. Under some circumstances this process can be reversed to generate disc micelles from vesicles. These processes may occur in the formation and nonequilibrium transformations of bile. PMID- 2210658 TI - Surface chemistry of phospholipid vesicles relevant to their aggregation and fusion. AB - A general description of those forces that are important in the stability of the lipid bilayer is presented. The analysis focuses on those that may change under conditions in which aggregation or fusion of vesicles or exchange of their molecules may occur. It is that class of membrane forces that is most likely to play a role in the process(es) that leads to the formation of cholesterol crystals in bile, which eventually grow into gallstones. A specific, hypothetical mechanism for cholesterol crystal nucleation based on vesicle fusion is also given. This mechanism is consistent with the principles of surface chemistry outlined. PMID- 2210659 TI - Chemical species of lipids in bile. AB - Bile salts, phospholipids and sterols are the major lipid species in bile. The common bile salts possess a steroid nucleus of four fused hydrocarbon rings with polar hydroxyl functions and an aliphatic side chain conjugated in amide linkage with glycine or taurine. Since the ionized carboxylate or sulfonate group on the side chain renders bile salts water soluble, they are formally classified as soluble amphiphiles. The common bile salts differ in the number and orientation of the hydroxyl groups on the steroid nucleus. Bile salts synthesized from cholesterol in the liver are called primary bile salts, which in humans are cholate, with three hydroxyl groups, and chenodeoxycholate, with two hydroxyl groups. Secondary bile salts are created by the action of intestinal bacteria on primary bile salts; deoxycholate, with two hydroxyl groups, and lithocholate, with a single hydroxyl group, are formed from cholate and chenodeoxycholate, respectively. "Tertiary" bile salts are the result of modification of secondary bile salts by intestinal flora or hepatocytes; in humans these are the sulfate ester of lithocholate and ursodeoxycholate, the 7 beta-epimer of chenodeoxycholate. Lecithin (diacylphosphatidylcholine), the major phospholipid in bile, is an insoluble, swelling amphiphile with a hydrophilic, zwitterionic phosphocholine head group and hydrophobic tails comprised of two long fatty acyl chains. Biliary lecithin is derived from the least hydrophobic hepatic lecithins and typically contains a saturated C-16 acyl chain in the sn-1 position and an unsaturated C-18 or C-20 acyl chain in the sn-2 position. Cholesterol, present solely as the nonesterified free alcohol, accounts for more than 90% to 95% of the sterols in bile.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210660 TI - Fluorescence assays to monitor membrane fusion: potential application in biliary lipid secretion and vesicle interactions. AB - Membrane fusion constitutes an essential, intermediate step in numerous cell biological processes, occurring for example during endocytosis, membrane recycling and exocytosis. Also less desirable events such as the infection of cells by animal viruses are mediated by membrane fusion during which the viral envelope merges with a cellular membrane, causing the expulsion of the viral nucleocapsid into the cytoplasm of the cell as an initial step in virus replication. Much of our current knowledge concerning the mechanism of membrane fusion has been derived from studies using simple artificial membranes, such as liposomes or phospholipid vesicles, as model systems. A most essential feature of these studies has been the development of membrane fusion assays that register in a sensitive and continuous fashion the mixing of membranes or the aqueous volumes initially enclosed by these membranes. Not only do these assays allow one to readily detect and quantify fusion, but they also provide the possibility to relate the kinetics of fusion to the rate by which certain molecular changes in membranes take place. Obviously, this insight is of relevance for understanding the mechanism of membrane fusion. The principles and applications of some representative assays that rely on the use of fluorescence spectroscopy will be discussed. Assays that monitor membrane mixing are commonly based on the detection of changes in resonance energy transfer efficiency or the relief of fluorescence self-quenching of appropriate fluorescent lipid analogs. Contents mixing assays rely on either the formation of a (aqueous-soluble) fluorescent complex or quenching of a fluorophore, encapsulated in one vesicle population, by a suitable quencher, entrapped in a second population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210661 TI - Molecular control of vesicle aggregation and membrane fusion: hypotheses on bile vesicles. AB - Molecular factors that control the aggregation and fusion of phospholipid vesicles are reviewed. These include membrane composition, vesicle size, various cations, membrane phase state, dehydrating agents and proteins. Several hypotheses are presented for the mechanism by which bile vesicles aggregate and fuse. It is proposed that phase-separated domains of cholesterol in the bile vesicle bilayer mediate the close approach of the vesicles and that molecular packing defects at the domain boundaries mediate hydrophobic interaction between and fusion of apposed membranes. The apposition or fusion of the membranes may provide the third dimension within which the cholesterol domains on apposed or collapsed membranes can begin to form the monohydrate crystal. Other mediators of aggregation and fusion are likely to be proteins that interact hydrophobically with the bile vesicle and diacylglycerol formed in the vesicles by phospholipase C action. Ca2+ is thought to enhance fusion by interacting with bile salts in the membrane or with membrane-associated proteins. PMID- 2210662 TI - Cholesterol packing, crystallization and exchange properties in phosphatidylcholine vesicle systems. AB - The properties of phosphatidylcholine/cholesterol vesicles have been studied extensively because of their relevance to the behavior of these components in cell membranes. At equilibrium, phosphatidylcholine bilayers are saturated when equimolar levels of cholesterol are incorporated; the cholesterol molecules interfere with the cooperative lateral interactions of the phosphatidylcholine acyl chains and restrict the fluidity relative to pure liquid-crystal phosphatidylcholine bilayers. Mixed cholesterol/phosphatidylcholine bilayers containing more than equimolar cholesterol are metastable; on storage excess cholesterol is released from the vesicles and forms cholesterol monohydrate crystals. This process models the formation of cholesterol gallstones in bile and the growth of the crystals probably involves, at least in part, diffusion of cholesterol molecules from the vesicle bilayer to the crystal surface. The cholesterol-phosphatidylcholine interaction energy in the lipid-water interface of the donor vesicle has a critical effect on the rate of this transfer process. PMID- 2210663 TI - Comparison of spontaneous phospholipid transfer between phospholipid vesicles and between phospholipid-bile salt mixed micelles. AB - Fluorescent-labeled N-(7-nitro-2,1,3-benzoxadiazol-4-yl)phosphatidylethanolamine was used to compare the spontaneous rates of phospholipid transfer between phospholipid vesicles and between phospholipid-bile salt micelles. The half times for transfer between the mixed micelles are 200 to 6,000 times faster than between vesicles, depending on the acyl chain length of the N-(7-nitro-2,1,3 benzoxadiazol-4-yl)phosphatidylethanolamine and the total lipid concentration. A kinetic analysis of the rates of phospholipid transfer between vesicles indicated that transfer occurs predominantly as soluble monomers moving through the water phase. Transfer between mixed micelles was found to occur by the same aqueous diffusion mechanism at low lipid concentrations, but at high lipid concentrations, transfer occurs predominantly during transient micelle collisions. The faster rate of transfer between mixed micelles relative to vesicles results both from the collision-dependent transfer and from an increase in the rate-limiting step for aqueous diffusion-phospholipid dissociation from the micelle surface. The relative contribution of collision-dependent transfer to the overall transfer rate increases with phospholipid acyl chain length and total lipid concentration. For the phospholipid species and mixed micelle concentrations normally found in the biliary tract, the predominant mode of transfer is predicted to occur by the collision-dependent mechanism. PMID- 2210664 TI - Cholesterol monomer activity and its role in understanding cholesterol saturation and crystallization. AB - Cholesterol in bile has been linked to the incidence of gallstone disease through the concept of supersaturation as measured by the cholesterol saturation index. The latter is a linear function of cholesterol concentration and is based on the assumption that all cholesterol in bile is solubilized and transported in bile salt-lecithin mixed micelles and in bile salt simple micelles. In light of the discovery of the cholesterol-lecithin vesicles as significant cholesterol carriers, there is a need to reevaluate this old concept. This study examined the feasibility of the silicone polymer uptake method for the direct determination of the cholesterol thermodynamic activity in model bile systems. In cases of unsaturation and near saturation, a linear relationship was observed between the cholesterol concentration in the silicone polymer at equilibrium and the cholesterol saturation index (the cholesterol concentration in the aqueous micellar solution at equilibrium/cholesterol monohydrate solubility in the same medium) for taurocholate and taurochenodeoxycholate systems either containing or not containing lecithin. In taurocholate-lecithin solutions supersaturated with cholesterol, the linear relationship continued to hold up to the point where vesicles started to form. Vesicle formation initiated a negative deviation from linearity. At constant lecithin concentration, the cholesterol thermodynamic activity at which vesicle formation began was a function of the taurocholate/lecithin ratio; the larger the taurocholate/lecithin ratio, the higher the cholesterol thermodynamic activity for the onset of vesicle formation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210665 TI - Separation and quantitation of cholesterol "carriers" in bile. AB - On the basis of phase equilibria theory and experimental data, we discuss the identity, separation and quantitation of cholesterol-solubilizing lipid aggregates in bile, trivially known as cholesterol "carriers." We first describe analogies (as well as lack of correspondence) between equilibrium phase diagrams of aqueous bile salt, lecithin and cholesterol systems and phase equilibria in native biles. At equilibrium, the possible number and types of different cholesterol "carriers" are limited by constraints placed by the phase rule. These "carriers" include simple micelles (bile salts without lecithin), mixed micelles (bile salts plus lecithin), a lecithin plus cholesterol lamellar phase composed of single bilayer structures (vesicles) or multilamellar structures (liquid crystals) and possibly fragments of a hexagonal phase. Clearly, in this context, cholesterol monohydrate crystals, no matter how small, cannot be considered "carriers." We also use a metastable "phase diagram" for aqueous taurocholate-egg yolk lecithin-cholesterol systems to interpret physicochemical studies on the formation and stability of native biles. In biliary lipid systems, bile salt monomers with or without simple bile salt micelles are present in the aqueous "phase" in equilibrium with mixed micelles/or vesicles. This bile salt concentration is designated the intermicellar concentration but actually represents the total nonmixed micellar/nonvesicular concentration of bile salts (i.e., bile salt monomers and simple bile salt micelles when present) and may be a value that falls below, equal to or above the critical micellar concentration of the bile salts. Experimental estimates of the intermicellar-intervesicular bile salt concentration in model systems are compared with the range of bile salt concentrations that has been used in the literature to separate the presently accepted cholesterol "carriers" (mixed micelles and vesicles) in both model and native biles. We also reinterpret published lipid compositions of phases separated from human bile, using both a nonequilibrium "phase diagram" and an equilibrium phase diagram for the model system, taurocholate-egg yolk lecithin cholesterol. From these analyses, we conclude that precise quantitation of cholesterol "carriers" in bile awaits methods to accurately determine the intermicellar-intervesicular concentration of bile salts in any individual bile, as well as advances in nonperturbing separatory procedures, and methods to control the thermal and temporal history of native bile samples. PMID- 2210666 TI - Supplemental putrescine reverses ethanol-associated inhibition of liver regeneration. AB - Biosynthesis of the polyamines, putrescine, spermidine and spermine, is required for DNA synthesis and liver regeneration after partial hepatectomy. Chronic ethanol consumption impairs polyamine synthesis during the prereplicative phase after partial hepatectomy. To determine whether this delay in polyamine synthesis contributes to ethanol's inhibition of liver regeneration, the ability of supplemental putrescine to improve regeneration in ethanol-fed rats was tested. Chronically ethanol-fed rats and isocalorically maintained controls underwent partial hepatectomy and were injected intraperitoneally with saline or putrescine (0.03 or 0.30 mmol/kg) at 0, 4, 8 and 12 hr after partial hepatectomy. Rats were killed at 24, 48 or 72 hr, 1 hr after exposure to [3H]thymidine, so that DNA synthesis could be estimated. DNA synthesis was significantly inhibited in ethanol-fed rats treated with saline compared with saline-treated pair-fed controls. Supplemental putrescine did not affect DNA synthesis in pair-fed rats. In contrast, putrescine significantly improved [3H]thymidine incorporation 24 to 72 hr after partial hepatectomy in ethanol-fed rats. Intraperitoneal injection of putrescine (1.2 mmol/kg) at the time of partial hepatectomy increased hepatic polyamine concentrations for the first 6 hr after partial hepatectomy despite significantly inhibiting the activity of ornithine decarboxylase, the rate limiting enzyme for polyamine synthesis, in both groups. Hepatic polyamine levels after putrescine injection were greater in ethanol-fed rats than in similarly treated controls. These data suggest that putrescine treatment triggers events that normalize DNA synthesis in ethanol-fed rats. These results confirm the hypothesis that ethanol's antiregenerative mechanism intimately involves inhibition of putrescine synthesis. PMID- 2210667 TI - Suppression of hepatic lymphokine-activated killer cell induction by murine Kupffer cells and hepatocytes. AB - Murine lymphokine-activated-killer cell activity was readily induced by culturing spleen cells with 10 U/ml of interleukin-2 for 4 days. In contrast, very little activity was generated under the same culture conditions when nonparenchymal liver cells were used as the responding cells. It was concluded that Kupffer cells produced prostaglandin and interferon alpha/beta, which suppressed lymphokine-activated-killer induction because (a) induction of lymphokine activated-killer activity from nonparenchymal liver cells was observed in the presence of indomethacin and anti-interferon alpha/beta antibody; (b) when adherent nonparenchymal liver cells, primarily Kupffer cells, were removed, lymphokine-activated-killer activity could be obtained with interleukin-2 alone; (c) coculture of Kupffer cells with nonadherent nonparenchymal liver cells in a two-chambered system inhibited lymphokine-activated killer cell induction in a dose-dependent manner; (d) exogenous prostaglandin E2 and interferon alpha/beta added at the start of culture inhibited interleukin-2-induced cytotoxicity and proliferation, whereas the other major prostaglandin species in the liver, prostaglandin D2, had little effect. These findings are distinctive with Kupffer cells because splenic macrophages did not exert such inhibition in parallel experiments. Moreover, the supernatant collected from the 24-hr culture of nonparenchymal liver cells contained greater than 20-fold more prostaglandin E2 and interferon alpha/beta than that from culture of spleen cells. In subsequent in vivo experiments, when interleukin-2 was given intraperitoneally to mice, the combination of indomethacin and anti-interferon alpha/beta antibody significantly enhanced lymphokine-activated-killer activity recovered from the liver.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210668 TI - HBV-DNA detection by gene amplification in acute hepatitis B. AB - Serum samples from 62 women, inadvertently infected with hepatitis B virus in an in vitro fertilization program, were tested for the presence of hepatitis B virus DNA using the polymerase chain reaction. Under conditions of a strict spatial separation of DNA extraction, amplification and product analysis, we succeeded in detection of as few as 360 hepatitis B virus particles per milliliter. Hepatitis B virus-DNA was detected with a high frequency during HBsAg and HBeAg antigenemia (98.5%) but also in the convalescent phase after appearance of antibody to HBsAg (18.2%). However, all patients with hepatitis B virus-DNA in convalescent sera were hepatitis B virus-DNA negative 3 to 6 mo later. All patients with HBeAg positive samples showed hepatitis B virus-DNA positivity by polymerase chain reaction. For acute hepatitis, gene amplification restores the relationship between HBeAg and hepatitis B virus-DNA observed in serum from chronic hepatitis B patients and calls attention to the prolonged presence of hepatitis B virus-DNA in serum after generally accepted criteria for resolution of the infection have been reached. PMID- 2210669 TI - Changes of serum hepatitis B virus DNA and aminotransferase levels during the course of chronic hepatitis B virus infection in children. AB - During a follow-up period of 3.2 +/- 1.6 (1 to 8.6) yr, 1,087 serum specimens from 230 HBsAg carrier children were tested for hepatitis B virus markers. Dividing the serum specimens into four groups according to the status of HBeAg and hepatitis B virus DNA, the frequency of abnormally elevated ALT levels in serum was in the following order: HBeAg(+)/hepatitis B virus DNA(-) serum (60%), HBeAg(-)/hepatitis B virus DNA(+) serum (53%), HBeAg(+)/hepatitis B virus DNA(+) serum (41%), HBeAg(-)/hepatitis B virus DNA(-) serum (11%). Analysis of the data before HBeAg clearance showed that both a high serum ALT level and a low serum hepatitis B virus DNA level correlated with an imminent clearance of HBeAg. Approximately two thirds of children with serum ALT levels higher than 100 IU/L cleared HBeAg within the following year. Clearance of HBeAg occurred within the following year in 65% (13 of 20) of cases with serum hepatitis B virus DNA level less than or equal to 1,000 pg/ml, in contrast to 19% (30 of 157) of those with serum hepatitis B virus DNA level greater than 1,000 pg/ml. Among 53 children who lost HBeAg and hepatitis B virus DNA during follow-up, only nine cases did not have an identified period of abnormal serum ALT levels. For the remaining 44 children, abnormal serum ALT levels fell to normal with clearance of both HBeAg and hepatitis B virus DNA in 33 children but remained elevated in the remaining 11 cases after seroconversion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210670 TI - Hepatocyte plasma membrane glycosphingolipid reactive with sera from patients with autoimmune chronic active hepatitis: its identification as sulfatide. AB - Sera from patients with autoimmune chronic active hepatitis were found to contain IgG-class antibody to the acidic glycosphingolipid fraction from rabbit hepatocyte plasma membrane by solid-phase enzyme-linked immunosorbent assay. Using serum positive for the antibody as a probe, we isolated the target antigen by Iatrobeads column chromatography. Analysis by thin-layer chromatography and negative ion fast atom-bombardment mass spectrometry revealed that the antigen was sulfatide. The presence of antisulfatide antibody was also confirmed by immunoblotting. The reactivity of the serum with sulfatide was diminished by preincubation of the serum with galactosylceramide-6-sulfate and sulfatide, indicating that the antibody reacted with sulfated galactosylceramide regardless of the position of the sulfate residue. The antibody was found in 92.3%, 42.9%, 15.8%, 14.2%, 0% and 0%, respectively, of patients with autoimmune chronic active hepatitis, primary biliary cirrhosis, cirrhosis, systemic lupus erythematosus, chronic active hepatitis and chronic persistent hepatitis. Thus antisulfatide antibody was characteristic of autoimmune-type chronic liver diseases. Antisulfatide antibody was absorbed by rabbit hepatocyte plasma membrane. Preincubation of sera with sulfatide immobilized on Sepharose decreased their reactivities with not only sulfatide but also rabbit plasma membrane and rat hepatocytes. Therefore sulfatide may be a target antigen of the antibody to hepatocyte surface membrane. PMID- 2210671 TI - The auditory P300 event-related potential: an objective marker of the encephalopathy of chronic liver disease. AB - Recently many variants of electroencephalogram-evoked responses have been studied as potential diagnostic aids in the detection and evaluation of hepatic encephalopathy. This study assesses the value of the auditory P300 event-related potential--a slow component of the auditory evoked response--as a tool in this field. Twenty-one nonencephalopathic and 12 encephalopathic (grade 1/2) cirrhotic patients and 26 controls were assessed clinically and psychometrically. Electroencephalogram spectral analysis and visual evoked response recordings were also conducted. An auditory P300 wave was elicited using the standard two-tone discrimination paradigm. The latency and amplitude of this wave were measured. The latency of the P300 was found to be significantly increased in the encephalopathic patients compared with both nonencephalopathic cirrhotic and control groups (p less than 0.05). Amplitude of the wave was decreased in both nonencephalopathic and encephalopathic patients, but this was not statistically significant. This study suggests that the latency of the P300 is a good marker of grades 1 and 2 clinical hepatic encephalopathy. The delays in the P300 latency may indicate that encephalopathic patients have a deterioration of their stimulus evaluation abilities. PMID- 2210672 TI - Monomicrobial nonneutrocytic bacterascites: a variant of spontaneous bacterial peritonitis. AB - Spontaneous bacterial peritonitis is diagnosed when (a) the ascitic fluid culture is positive, (b) the ascitic fluid neutrophil count is greater than or equal to 250 cells/mm3 and (c) there is no evident intraabdominal surgically treatable source for infection. Few details are available regarding the variant of ascitic fluid infection in which the culture grows bacteria (pure growth of a single type of organism), but the neutrophil count is less than 250 cells/mm3. In this prospective study of 138 episodes of culture-positive spontaneously infected ascites detected in 105 patients, 44 (31.9%) were episodes of "monomicrobial nonneutrocytic bacterascites" compared with 94 (68.1%) episodes of spontaneous bacterial peritonitis. Seventeen patients had both types of infection. The infection-related mortality and hospitalization mortality were similar between the two groups. Patients with bacterascites appeared to have less severe liver disease. In 62% of bacterascites episodes in which a second paracentesis was performed before any treatment the fluid spontaneously became sterile without development of ascitic fluid neutrocytosis. Thirty-eight percent of patients with bacterascites (who underwent a second paracentesis before treatment was started) progressed to spontaneous bacterial peritonitis--sometimes within a few hours. The concentration of the chemoattractant C5a was not decreased in the ascitic fluid of the bacterascites patients; this excludes ascitic fluid C5a deficiency as the explanation of the lack of neutrocytosis. Monomicrobial nonneutrocytic bacterascites is a common variant of ascitic fluid infection that may resolve without treatment or may progress to spontaneous bacterial peritonitis. PMID- 2210673 TI - Norfloxacin prevents spontaneous bacterial peritonitis recurrence in cirrhosis: results of a double-blind, placebo-controlled trial. AB - Eighty cirrhotic patients who had recovered from an episode of spontaneous bacterial peritonitis were included in a multicenter, double-blind trial aimed at comparing long-term norfloxacin administration (400 mg/day; 40 patients) vs. placebo (40 patients) in the prevention of spontaneous bacterial peritonitis recurrence. At entry, both groups were similar with respect to clinical and laboratory data, ascitic fluid protein and polymorphonuclear concentrations, number of previous episodes of spontaneous bacterial peritonitis and causative organisms of the index spontaneous bacterial peritonitis. Norfloxacin administration produced a selective intestinal decontamination (elimination of aerobic gram-negative bacilli from the fecal flora without significant changes in other microorganisms) throughout the study in six patients in whom the effect of norfloxacin on the fecal flora was periodically assessed. Fourteen patients from the placebo group (35%) and five from the norfloxacin group (12%) developed spontaneous bacterial peritonitis recurrence during follow-up (chi 2 = 5.97; p = 0.014) (mean follow-up period = 6.4 +/- 0.6 mo; range = 1 to 19 mo). Ten of the 14 spontaneous bacterial peritonitis recurrences in the placebo group and only one of the five spontaneous bacterial peritonitis recurrences in the norfloxacin group were caused by aerobic gram-negative bacilli (chi 2 = 8.87; p = 0.0029). The overall probability of spontaneous bacterial peritonitis recurrence at 1 yr of follow-up was 20% in the norfloxacin group and 68% in the placebo group (p = 0.0063) and the probability of spontaneous bacterial peritonitis recurrence caused by aerobic gram-negative bacilli at 1 yr of follow-up was 3% and 60%, respectively (p = 0.0013).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210674 TI - Relative frequencies of portosystemic pathways and renal shunt formation through the "posterior" gastric vein: portographic study in 460 patients. AB - Percutaneous transhepatic portography was carried out in 460 patients with portal hypertension to study various collateral routes. Besides the left gastric vein, which was the most frequent collateral route and feeder of esophageal varices, a distinct vein located between the left gastric vein and the short gastric vein constituted a major collateral route in 191 patients (42%). In terms of frequency, this vein was more significant than the short gastric (34%) and the paraumbilical vein (24%) as a collateral route. We propose that this previously anonymous vein be called the "posterior gastric" vein because it runs posterior to the stomach. This vein also formed a renal shunt, a common cause of encephalopathy, in 43 (23%) of the 191 patients; the relative frequency of renal shunt formation by this vein was significantly greater than that by the left gastric vein (12%) and the short gastric vein (18%). PMID- 2210675 TI - Albumin absorption and protein secretion by the gallbladder in man and in the pig. AB - To study albumin absorption by the gallbladder in man, an in vitro model was first established in the pig and compared with in vivo function in the same species. Water and electrolyte transport and 125I-albumin absorption and protein secretion in vivo and in vitro were compared. Then similar in vitro studies were performed on human gallbladders obtained at surgery. The in vivo study in the pig was performed without disturbing the gallbladder except to tie a cannula in the cystic duct end. The in vitro model was identical in the pig and human gallbladders. Gallbladders were excised using a technique causing minimal injury and anoxia. They were oxygenated on both mucosal and serosal surfaces in a temperature-controlled environment. Luminal and external bath test solutions consisted of modified Ringers bicarbonate with added glucose; luminal solutions also contained 125I-albumin from different species, depending on the study. Active absorption of sodium and water occurred in both types of studies in the pig but in vivo absorption rates were considerably greater than in vitro rates. Albumin absorption in vivo was substantial; although present in vitro, the absorption of albumin was diminished relatively more than electrolyte transport rates. Protein secretion rates into the gallbladder were similar in vitro and in vivo. The results of studies in the human gallbladders in vitro were similar to the pig, except albumin absorption was greater. Some human gallbladders were obtained from control patients and some from patients with cholesterol gallstones. There were no significant differences between the two groups for any of the variables studied; however, the numbers were small and some control gallbladders were not normal gallbladders. PMID- 2210676 TI - Transport of chenodeoxycholic acid and its 3-alpha- and 7-alpha-sulfates by isolated perfused rat liver. AB - In patients with cholestasis, levels of sulfated bile acids rise. Sulfate esters of chenodeoxycholic acid are the most abundant of these bile acid sulfates. These compounds are taken up by the liver and excreted into bile, although their plasma clearance and biliary excretion are reduced compared with that of unsulfated bile acids. It is not clear whether this is due to differences in intrinsic hepatic uptake or biliary excretion. In the present study, single-pass transport kinetics of chenodeoxycholic acid 3-alpha-sulfate, chenodeoxycholic acid 7-alpha-sulfate and unsulfated chenodeoxycholic acid were quantified in isolated perfused rat liver. Influx of the 7-alpha- and 3-alpha-sulfated derivatives was 57% and 20% that of chenodeoxycholic acid, respectively. These three compounds bound to albumin equally well, indicating that this was not a factor in their differential uptake. Although single-pass extraction of material taken up by the liver was identical. There was no difference in bile flow or biliary excretion of material taken up by the liver was identical. There was no difference in bile flow or biliary excretion rate, regardless of which bile acid sulfate was tested. These results indicate that the low plasma elimination of sulfated bile acids previously observed by others can be explained by low hepatic influx. The diminished transport into liver resulting from sulfation could lead to enhanced elimination of bile acids by the kidney. PMID- 2210677 TI - Amyloid deposition in intrahepatic large bile ducts and peribiliary glands in systemic amyloidosis. AB - Amyloid deposition in the hepatic parenchyma and portal tracts in the liver is well known in systemic amyloidosis. We recently experienced an autopsy case of systemic amyloidosis presenting the amyloid deposits in the intrahepatic biliary tree. This experience prompted us to survey 19 autopsy cases of systemic amyloidosis. Amyloid deposition was found just under the lining epithelium of the intrahepatic large bile duct in 10 of 19 cases and around the peribiliary glandular acini in 7 of the 19 cases, respectively. Amyloid deposition in the intrahepatic large bile duct and peribiliary glands was positively correlated with the degree of amyloid deposition in the liver but not with type of amyloid protein. Double-staining of amyloid and vascular endothelium disclosed that amyloid deposition was more closely related to the inner part of the peribiliary vascular plexus and to the vascular plexus encircling the peribiliary glands than the lining biliary epithelium and peribiliary glandular acinar cells themselves. The exact pathogenesis of amyloid deposition in these anatomical components, however, remains unclear. Although our cases failed to show any overt clinical symptomatologies related to amyloid deposition in these biliary components, it seems conceivable that more massive amyloid deposition in these anatomical components could give rise to some clinical symptoms. PMID- 2210678 TI - Diagnostic value of brush cytology in the diagnosis of bile duct carcinoma: a study in 65 patients with bile duct strictures. AB - Malignant strictures of the extrahepatic bile ducts are difficult to distinguish from benign strictures, particularly in patients with primary sclerosing cholangitis. Because attempts at diagnosing small cancers with fine-needle aspiration biopsy are not possible in the absence of an associated mass lesion and because the sensitivity of exfoliative biliary cytology is controversial, brush cytology has been used as a potential means of establishing a specific diagnosis of bile duct carcinoma. Herein we report our experience with this technique when performed on 65 patients over a 5-yr period. Each had at least one brushing. Thirty-seven were found to have bile duct carcinoma and 28 were found to have benign strictures. Of these 37, the first brushing was positive for malignancy in 15 (40%), whereas four (11%) had cells suspected but not diagnostic of malignancy. Thirteen patients with bile duct carcinoma whose initial brushings were negative for malignancy had second brushings. Of these, five (38%) had malignant cells, whereas three (24%) yielded suspicious cells. Three of the eight whose first two brushings were negative for malignancy were found to have malignant cells on the third brushing. In contrast, of the 28 patients with benign strictures, malignant cells were never found. However, in two patients, suspicious cells were reported with the first but not the second brushing. A single negative or suspicious cytological finding decreased the probability of bile duct carcinoma to 43%. Two and three sequential negative tests reduced the probability to 32% and 0%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210680 TI - Spontaneous bacterial peritonitis: prevention and therapy. PMID- 2210679 TI - Review of hepatic imaging and a problem-oriented approach to liver masses. AB - We believe that imaging of the liver is complicated. The sporadic appearance of incidental benign lesions and variability in scanning techniques, equipment and artifacts add difficulties to the evaluation of liver masses. Therefore we emphasize the need to define the problem for which the patient is being imaged. This information helps in choosing the procedure of choice and the technique needed to give the most expedient, accurate answer. This will also help apply the lowest risk and most cost-efficient care. Imaging algorithms vary depending on the suspected pathological conditions. Dynamic bolus-enhanced CT is the modality of choice in most situations. Tc99m sulfur-colloid liver-spleen scans are helpful in patients with suspected FNH, and Tc99m-tagged-RBC-SPECT scans are recommended to confirm cavernous hemangiomas. Cysts are easily confirmed by US. Although MRI is competitive with CT, it has not become a primary modality because of cost, availability, patient selection and variability of scanner capabilities among the many manufacturers and models. It is hard to predict what future development of imaging techniques will bring. Many feel that significant advances have plateaued. Time and money will more likely be concentrated on improving image resolution, speed of scanning and ability to transfer this information to sites outside of the radiology department. In addition to faster scanning, we expect to soon have available safe intravenous and enteric contrast agents for MRI. Certainly this will lead to a new round of investigations to compare MRI with CT scanning. PMID- 2210681 TI - Endoscopic ligation of esophageal varices: an endoscopist's opinion. PMID- 2210682 TI - Methotrexate hepatotoxicity and the premature reporting of Mark Twain's death: both greatly exaggerated. PMID- 2210683 TI - Effects of oxygen inhalation in ascitic cirrhotic patients: therapeutic implications? PMID- 2210684 TI - Interferon treatment and ALT normalization concomitant with ongoing viral replication. PMID- 2210685 TI - The American Association for the Study of Liver Diseases. Postgraduate course & 41st annual meeting. November 3-6, 1990, Chicago, Illinois. Abstracts. PMID- 2210686 TI - Salvage chemotherapy for non Hodgkin's lymphoma of unfavourable histology with a combination of CCNU and vinblastine. AB - Twenty patients with relapsed or refractory, intermediate or high grade non Hodgkin's lymphoma were treated with a combination of CCNU and vinblastine. Complete responses occurred in four patients (20 per cent), partial responses in eight (40 per cent), for an overall response rate of 60 per cent. The regimen was more effective in patients with high grade lymphoma, absence of constitutional symptoms, better response to prior treatment. Duration of response was 4, 8, 16, 30 months for complete responders; 2, 2, 6, 6, 6, 8, 9, 14 months for partial responders. This combination regimen seems at least as effective as most of other regimens utilized in salvage treatment of non Hodgkin's lymphomas, with a very acceptable toxicity. PMID- 2210687 TI - Combination of interferon and dexamethasone in refractory multiple myeloma. AB - The present pilot study was designed to analyse the efficacy and toxicity of the association of interferon (IFN) and dexamethasone (Dx) in 32 resistant and relapsed myeloma patients. Among the evaluable cases, 15 (68 per cent) responded to treatment (32 per cent achieved an objective response--OR--and 36 per cent a partial response--PR--), the 'remission' status lasting for more than one year in six of them. Moreover, four out of the seven OR patients showed a reduction in B.M. plasma cells to less than 5 per cent. Five out of 11 patients that were previously refractory to VBAD, that includes high dose dexamethasone (Dx), responded to IFN-Dx. The protocol was generally well tolerated with only four patients discontinuing therapy due to adverse effects. The present results show that the combination IFN + Dx is a promising therapeutic approach for patients with refractory myeloma. PMID- 2210688 TI - Heterogeneous expression of proto-oncogenes in Hodgkin's disease derived cell lines. AB - The expression of 20 proto-oncogenes was analysed by Northern blotting in four cell lines derived from patients with Hodgkin's disease (L428, L540, CO and DEV) and compared to lymphoid and myeloid leukemia cell lines and normal hematopoietic cells. Expression of the proto-oncogenes c-myc, p53, c-jun, pim-1, lck, c-syn, c raf and N-ras were detected in Hodgkin's disease derived cell lines and in normal hematopoietic cells. Transcripts of the proto-oncogene c-met were detected in the Hodgkin's derived cell lines L428 and L540 but not in the lymphoid or myeloid leukemia cell lines or in tonsil cells, peripheral blood mononuclear cells and granulocytes. Expression of the proto-oncogenes N-myc and lck were observed in the Hodgkin's derived cell line CO which express T cell receptor genes and in the T cell lines JM and CEM. L428 cells and CO cells expressed aberrant transcripts of the c-fes proto-oncogene. Thus Hodgkin's disease derived cell lines are heterogeneous in their expression pattern of proto-oncogenes, expressing normal and aberrant transcripts of proto-oncogenes which are not found in untransformed hematopoietic cells. PMID- 2210689 TI - Ifosfamide and mitoxantrone (I-M) in relapsed and refractory high grade non Hodgkin's lymphoma and Hodgkin's disease. AB - Fifty-five patients, initially diagnosed as having advanced high grade non Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) refractory to first-line treatment or in relapse, were treated with ifosfamide 6 g/m2, infused over 48 h, followed by mitoxantrone 12 mg/m2. The regimen repeated at three-weekly intervals. Of 32 patients with NHL evaluable for response, 10 (31 per cent) achieved complete remission and five partial remission, giving an overall response rate of 47 per cent. Two patients subsequently went on to bone marrow transplant (BMT)--one allogeneic and the other autologous. Of 17 patients with HD evaluable for response, six (35 per cent) achieved complete remission and six partial remission, giving an overall response rate of 71 per cent. Two of this group also went on to BMT (both autografts). The principal toxicity was neutropenia, though central nervous system changes were observed in 10 patients. Given the need to offer alternative treatment of patients in these categories, this combination (I-M) is clearly of value in relapsed patients especially where therapeutic options are limited because of previous multi-drug treatment. PMID- 2210690 TI - Clinical features associated with transformation of cerebriform T-cell lymphoma to a large cell process. AB - Some patients with cerebriform T-cell lymphoma (CTCL) undergo morphologic transformation to a large cell lymphoma. From a series of 113 patients with CTCL, 22 patients were identified with transformed CTCL. Stages of involvement at diagnosis were: I (seven), II (four), III (four), IV (seven). Nine patients had transformation at the initial diagnosis while the median time from diagnosis to transformation in the other 13 patients was 16 months (range: 3 months-6 years). Thirteen had transformation extracutaneously: lymph nodes (eight), central nervous system (two), and other extranodal sites (three). T cell markers were identified in all cases; of 15 cases with complete phenotypes, there were eight T helper, three T-suppressor, and four aberrant T phenotypes. Serology for human T leukemia virus-I (HTLV-I) was negative in eight patients tested. Median survival from diagnosis was 27 months compared to 53 months in 53 patients without transformation (p = 0.003). Despite combination chemotherapy in 12 patients following transformation, median survival after transformation was 12 months and only 7 months with extracutaneous disease. The likelihood of transformation could not be predicted by the initial histology, immunophenotype, or stage of disease. PMID- 2210692 TI - Impact of involuntary outpatient commitment on the revolving-door syndrome in North Carolina. AB - Involuntary outpatient commitment has been used as a means of treating so-called revolving-door patients in the community and allowing them to experience the positive aspects of social and community life that stability can bring. To study the impact of North Carolina's revised outpatient commitment law on institutionalization rates, the authors measured state hospital admissions and days of hospitalization within a three-year period for all patients committed to outpatient treatment during that period. Statistically significant decreases occurred in both measures; the biggest percent reduction occurred in admission rates. PMID- 2210691 TI - Expression of differentiation and adhesion molecules in sporadic Burkitt's lymphoma. AB - The phenotypic features of 44 cases of sporadic Burkitt's lymphoma (BL) were investigated by monoclonal antibodies (MoAbs). The majority of cases were positive for HLA-DR (97 per cent), CD19 (100 per cent), CD20 (92 per cent) and CD37 (83 per cent) pan-B markers, in accordance with the B-cell derivation of the tumour; the B-cell restricted markers CD21, CD22 and FMC7 reacted with 28 per cent, 66 per cent and 75 per cent of cases, respectively. Of the mantle zone B cell specific MoAbs, CD1c was always negative, whereas CD23 and 2.7 were positive with one and two cases, respectively. CD39 was weakly reactive on two specimens, one of which was CD23+. The germinal centre specific MoAbs CD10 and CD77 (Burkitt's lymphoma antigen) displayed a heterogeneous pattern of reactivity and allowed to identify 4 subgroups: CD10+/CD77+ (44 per cent), CD10+/CD77- (15 per cent), CD10-/CD77+ (36 per cent) and CD10-/CD77- (5 per cent). Of 15 cases tested for the expression of CD11a and CD18 lymphocyte-function-associated (LFA-1) antigens and their ligand ICAM-1 (CD54), seven were positive and six negative for the three markers, while the other two cases expressed alternatively the two molecules. Analysis of the putative normal BL cell counterpart, identified with the CD77 marker in normal lymphoid tissues, showed that all CD77+ B-cells were constitutively CD11a+/CD18+, suggesting that BLs are likely to arise from a LFA-1 positive B-cell and may down-regulate these molecules during neoplastic transformation. PMID- 2210693 TI - Quantifying undiagnosed organic mental disorder in geriatric inpatients. AB - Organic mental disorder often goes undetected in geriatric patients who have coexisting psychiatric symptoms. To determine the prevalence of organic mental disorders in geriatric patients admitted to a large metropolitan psychiatric inpatient service, charts for 95 patients over the age of 60 were reviewed, and diagnoses at admission and discharge were compared. Despite the facility's admission policy of excluding patients with only organic mental disorder, 32 patients required evaluation for organic mental disorder during hospitalization, and on reevaluation 15 patients received a primary diagnosis of organic mental disorder. The author discusses the mental health care and fiscal considerations of accurately assessing geriatric patients, especially in the context of the new federal regulations prohibiting most nursing home admissions for mentally ill patients. PMID- 2210694 TI - Characteristics of pathological gamblers identified among patients on a psychiatric admissions service. AB - A total of 105 patients admitted to a psychiatric admissions service for adults were screened for pathological gambling using the South Oaks Gambling Screen, a valid, reliable instrument for identification of this disorder. Seven of the 105 patients were identified as pathological gamblers, and ten were children of problem gamblers, rates that are higher than those for the general population. Pathological gamblers identified in this study had a broad range of primary diagnoses, including schizoaffective disorder, paranoid schizophrenia, major depression, and organic personality disorder. A high rate of pathological gambling (11 percent) was found among patients with a secondary diagnosis of psychoactive substance use disorders. PMID- 2210695 TI - Sensitizing mental hygiene therapy aides to the needs of patients' relatives. PMID- 2210696 TI - Development of a psychiatric home visit module for student training. PMID- 2210697 TI - Former patients as peer counselors on locked psychiatric inpatient units. PMID- 2210698 TI - Improvisational drama groups in an inpatient setting. PMID- 2210699 TI - Activities of psychiatric inpatients during their first hospital pass. PMID- 2210700 TI - Parent empowerment. PMID- 2210701 TI - California discharge data. PMID- 2210702 TI - Why patients smoke. PMID- 2210703 TI - Group homes and crime. PMID- 2210704 TI - Schizophrenia and related psychotic disorders. PMID- 2210705 TI - Disease and dysfunction: the value of axis V. PMID- 2210706 TI - The media and homeless mentally ill persons. PMID- 2210707 TI - Monitoring insanity acquittees: Connecticut's psychiatric security review board. AB - In 1985 Connecticut established an administrative psychiatric security review board to monitor the postverdict disposition of defendants found not guilty by reason of mental disease or defect. The five-member board may confine an insanity acquittee in a mental hospital, grant temporary leave, order conditional release, and terminate confinement or conditional release. Judicial review is required before a patient is discharged from the board's custody. Between 1985 and 1989, a total of 173 insanity acquittees were under the board's jurisdiction; most were hospitalized in state psychiatric facilities. The authors discuss issues that must be addressed in creating a psychiatric security review board, including the conflict between protecting the public and treating insanity acquittees, clinicians' resistance to treating these patients, and problems posed by patients who do not appear to be mentally ill or who are well known to the public. PMID- 2210708 TI - The formal treatment contract in the inpatient management of borderline personality disorder. AB - Formal, written contracts between the patient and the treatment team have been shown to be useful in the inpatient management of borderline personality disorder by fostering a therapeutic alliance, containing dangerous behavior, and protecting the integrity of the treatment. The author discusses the advantages and disadvantages of such contracts and points out several common contractual errors, including making a contract too restrictive, allowing the contract to substitute for psychotherapy, and using the contract as a means of defense or punishment. She provides 12 guidelines, for formulating successful contracts, beginning with the need to clearly state the purpose of the treatment plan mutually agreed on by patient and staff. PMID- 2210709 TI - The effect of borderline personality disorder on the hospital course of affective illness. AB - Two groups of patients with affective disorders, one group with a coexistent axis II diagnosis of borderline personality disorder and one group without, were compared to determine if the presence of borderline personality disorder affects the hospital course of patients with affective illness. Response to hospital treatment was assessed using standard psychiatric rating scales administered at admission, after one week of hospitalization, and before discharge. Although the patients with borderline personality disorder were more severely impaired than the comparison group, they were as likely as patients without the disorder to improve over the course of hospitalization. PMID- 2210710 TI - The myriad medication mistakes in psychiatry: a consumer's view. AB - Many consumers of mental health services suffer needlessly as a result of being given the wrong medication or the wrong dosage of the right medication or from other mistakes involving medication. The author, a consumer of mental health services for many years, discusses seven common medication mistakes: incorrect prescribing as a result of misdiagnosis, excessive dosages of medications, too many drugs, downplaying side effects, overlooking the consumer's expertise, discouraging consumers from learning about their medications, and the prescription-sheet relationship between psychiatrist and consumer. She concludes that although mental health professionals should listen more attentively to consumers, consumers bear the major responsibility for seeing that mistakes in their medication are corrected. Thus they must continue to speak up, raise questions, and keep informed. PMID- 2210712 TI - The Human Genome Project. PMID- 2210711 TI - Improving the validity of measures of patient satisfaction with psychiatric care and treatment. AB - Surveys of consumer satisfaction with psychiatric services are frequently included in program evaluations, ostensibly providing the patient's perspective. However, the consistently high levels of satisfaction reported, despite a wide variety of measures, suggest that these surveys may be of questionable validity. Recognizing that most surveys ask patients to rate aspects of care that professionals feel are important, the authors used a focus-group method to generate attributes of ideal care from the patient's viewpoint. A pool of 50 patient-generated items were rated for importance by a second group of inpatients on locked units of a provincial psychiatric hospital. A factor analysis and mean importance ratings identified interpersonal relations with staff as a key factor of patient satisfaction. The authors designed a seven-item measure of satisfaction based on this key factor. PMID- 2210713 TI - Genetic study of the Evens, an ancient human population of eastern Siberia. AB - Three territorial subgroups of reindeer breeders, fishermen, and fur hunters living under conditions of partial isolation in remote parts of the Yakut ASSR, have been investigated with respect to polymorphic genetic systems. Analysis of covariance matrices containing allele frequencies in an array of 12 loci for a large sample of Evens, Nganasans, and reindeer Chukchi indicates that the genetic relationships support known phylogenetic, linguistic, and historical events. PMID- 2210714 TI - Migration and genetic structure in Northumberland. AB - To understand the genetic variation that occurs among regions of northern England, we estimated migration from places of birth and residence in the last two generations for a sample of 1367 families in Northumberland. There has been an increase in kinship among regions, compatible with the increased mobility of recent decades, but the kinship patterns suggest that any regional gene frequency differences have remained relatively undiluted. Comparison of kinship and geographic distance between regions indicates that geographic location is an important determinant of genetic structure. PMID- 2210716 TI - Secular changes in stature in southern Portugal between 1930 and 1980 according to conscript data. AB - Stature of conscripts from four regions of southern Portugal was evaluated in a secular perspective. Data were drawn from the draft records for each decade between 1930 and 1980, a period that corresponds to a decisive expansion of industry and urbanization. In each region conscripts were divided into two groups according to their area of birth: urban or rural. A secular shift was apparent in every region, affecting conscripts of both urban and rural extraction. However, gains in stature were greater in the littoral than in the hinterland regions, where agriculture still employs a large percentage of the population. In each region the urban conscripts experienced greater secular gains than their rural counterparts. The secular shift was more pronounced among the short-stature segments of the populations; percentages of conscripts below a height of 160.0 cm dropped in a striking manner throughout the period under investigation. Despite the paucity of reliable information on the anthropometric and biodemographic characteristics of the Portuguese population, the secular gains were found to be associated with infant mortality and total death rate in the four regions. Compared to other Western European populations, the secular growth of the Portuguese proceeds at a slower pace, even when comparisons are made within the group of Latin countries that share a common linguistic and cultural heritage in addition to the shortest statures in Europe. PMID- 2210715 TI - Immunoglobulin haplotypes: markers of reproductive success? AB - Immunoglobulin haplotypes are highly polymorphic and are useful for analyses of both macro- and microdifferentiation of populations. The origins of this diversity are not known, but recent reports suggest strong selection at this locus. Increased rates of first-trimester spontaneous abortions have been reported when parents share GM phenotypes. Reduced fertility has been observed in mixed European descent white and Hutterite populations when both parents share immunoglobulin haplotypes. Population samples with completed family information and GM haplotype data are rare; the objective here is to provide this information on another sample. A sample of 242 Mennonite couples with mothers older than 40 years was divided into 3 groups of matings based on how many haplotypes were shared: 0, 1, or 2. The distribution of mean completed family sizes for the three groups were 3.35 +/- 1.85 (n = 23), 3.47 +/- 1.69 (n = 128), and 3.37 +/- 1.60 (n = 91), respectively; these values were not significantly different (F = 0.145, p = 0.865). The log-rank test was used to compare the time-to-next-birth curves. The intervals between first and later births (2-4 births) were not significantly different for the three subgroups either. There is also only limited evidence for segregation distortion in another sample of 923 offspring (in which at least one parent is heterozygous. PMID- 2210717 TI - Twinning rates in a rural area of Bangladesh. AB - In this study we investigate the incidence of twin births over a period of 16 years in a rural area of Bangladesh using data from the Demographic Surveillance System of the International Centre for Diarrhoeal Disease Research. Over the study period twinning rates fluctuated between 7.8 and 11.2 per 1000 live births. The twinning rate was strongly correlated with maternal age; the rate for mothers over 35 years of age was about 3 times higher than for mothers younger than 20 years. The variation in twinning rate with maternal age is due to the variation in dizygotic twinning; the rate of monozygotic twinning is almost constant for all ages. Twinning rates were higher in the treatment area than in the comparison area after controlling for maternal age and parity. The rates were lower for monozygotic twinning and higher for dizygotic twinning in the treatment area than in the comparison area. Seasonality was observed for both twins and singletons, but the peak for twinning precedes that for singleton births by more than a month. PMID- 2210718 TI - Surname repetition and isonymy in northeastern Hungarian marriages. AB - The repeated-pair (RP) approach to surnames in married couples is a measure of population subdivision resulting from the influence of lineagelike behavior in mate choice. An excess of RP over random RP implies limitations in mate choice and a reduction of genetic variability. Here we apply the RP method to data from the rural populations of Csaroda, Tiszaadony, and Tiszavid in northeastern Hungary. The results indicate small differences between RP and random RP for Tiszavid and somewhat larger differences for Tiszaadony and Csaroda. The excess of RP over random RP in Tiszavid, however, derives primarily from marriages simultaneously isonymous and repeating in only one lineage. The discrepancy between RP and random RP implies a small reduction in genetic variability. PMID- 2210719 TI - Nonrandom association of genetic markers in a sample of South African blacks. AB - According to classical genetic theory, allelic genes at one locus are expected to segregate and be manifested independently of allelic genes at another locus. At the population level any significant deviation from this general hypothesis resulting from specific biologic and genetic effects can be recognized in the form of nonrandom associations between genetic markers. The present data, consisting of 24 genetic polymorphisms determined from a sample of 998 unselected and unrelated South African blacks, offers an opportunity to test whether or not any such nonrandom associations exist between the genetic markers. After appropriate statistical calculations on the population data, we found that 13 pairs of genetic polymorphisms demonstrate a nonrandom association (statistically significant). Because the results cannot be explained in terms of known biologic mechanisms, we conclude that the associations observed could be due to random statistical effects (repeated application of the chi-square test) and/or to real (as yet unknown) biologic phenomena in the population studied. This tentative conclusion can serve as a guideline for more specific investigations. PMID- 2210720 TI - Distribution of hemoglobin E in several Mongoloid populations of northeast India. AB - Nine-hundred seventy-eight subjects from eight Mongoloid tribes of northeastern India were investigated for the distribution of hemoglobin phenotypes by starch gel electrophoresis. The sample included 157 Khasi and 24 Bodo from Cherrapunji (Meghalaya), 148, Rengma Naga and 81 Hmar of the Cachar district of Assam, 215 Adi from different subtribes, 216 Nishi, 79 Apatani, and a mixed group of 58 individuals from several other tribes of Arunachal Pradesh in northeast India. The frequency of HBB*E was found to be very low (0.01-0.02) in the Khasi, Naga, and Hmar tribes, whereas it varied from 0.06 to 0.18 among the tribes of Arunachal Pradesh. As expected, the Bodo group had a very high frequency of HBB*E (0.38), confirming earlier reports. It appears that the lack of HBB*E in the Austro-Asiatic (Khasi) and Naga-Kuki-Chin groups is probably due to the absence of malarial selection pressure as well as to isolation from their neighbors. PMID- 2210721 TI - Possible relations between sensitivity to phenylthiocarbamide and goiter. AB - Taste sensitivity to phenylthiocarbamide (PTC) using the Harris-Kalmus method was studied in 193 patients with thyroid disease and in a control sample of 311 individuals living in the Emilia area of Italy. The patients were classified according to the morphology of struma (mononodular, polynodular, diffuse) and to the toxic and nontoxic forms of goiter. Eighteen percent were nontasters in the control sample; 37.2% were nontasters in patients with polynodular goiter (toxic and nontoxic forms). Highly significant differences between the two groups were observed. The results obtained on this Italian sample agree with the conclusions of other studies. PMID- 2210722 TI - Analysis of digital patterns in the Basque valley of Deba: multivariate comparison with other populations. AB - Eighty-six females and 79 males from the Basque valley of Deba were analyzed with respect to their digital patterns using correspondence analysis. We found that there was a significant sexual difference for only one type of pattern, tented arch. Also, this population was compared with other Basque valley populations and with other Spanish populations. We found great variability among Basque subpopulations, despite their supposed common origin. Dermatoglyphic distances for some traits can be interpreted as genetic distances because there is high heritability of these traits. The results of the comparison between the Deba valley population and other Spanish populations showed that the Deba population is markedly distant from the other populations. PMID- 2210723 TI - Cancer-associated carbohydrates identified by monoclonal antibodies. AB - "New" carbohydrate structures on the surface of or secreted by cancer cells, identified as epitopes by monoclonal antibodies, are reviewed. These structures may represent the accumulation of precursor chains because of decreased activity of synthesizing enzymes, the production of new oligosaccharides due to increased or aberrant glycosylation of carbohydrate chains, a change in density of carbohydrates on the cell surface, or exposure of chains usually covered by other structures. Alterations in glycolipid synthesis include aberrant fucosylation and/or sialyation of the lacto series, sialylation or fucosylation of the globo series, and sialyation of the ganglio series. Many of these carbohydrate epitopes have become useful for the diagnosis, prognosis, and monitoring of patients with cancer. Some of the important markers include CA 15.3, CA 19.9, CA 50, CA 125, CA 242, MCA, SLEX, etc. Incomplete glycosylation of O-linked mucin oligosaccharide is recognized as the important "cancer antigen" B72.3, which is sialyated Tn. The oligosaccharide components of alpha-fetoprotein, carcinoembryonic antigen, and epidermal growth factor receptor are also reviewed. In many instances the glycosylation seen in cancer cells or their products reflects patterns seen during normal development. Thus, cancer-associated oligosaccharides are oncodevelopmental in nature. The biologic significance of carbohydrates on cell surfaces is not known, but several possibilities include a role in cell to cell recognition, intracellular processing of glycoproteins, cell activation, and ability of cancer cells to metastasize. PMID- 2210724 TI - Identification and fine structure of proliferating hepatocytes in malignant and nonmalignant liver diseases by use of a monoclonal antibody against DNA polymerase alpha. AB - To analyze the process of liver regeneration and the initiation of hepatocellular carcinoma (HCC), we studied histochemically the morphologic features of proliferating parenchymal cells stained for DNA polymerase alpha (DPA), in 31 patients with various diseases, by use of a monoclonal antibody against DPA. In specimens from patients with acute viral hepatitis with confluent necrosis, most stained hepatocytes were small, with basophilic cytoplasm, and were located next to the necrotic areas. Under electron microscopy, stained granules were seen in the nucleus. Most stained hepatocytes had immature organelles. In specimens from patients with cirrhosis of the liver, the number of stained hepatocytes greatly differed in different pseudolobules. In specimens from patients with adenomatous hyperplasia, stained hepatocytes, mostly small and basophilic, were found diffusely; electron microscopy showed slightly indented nuclei with a few organelles and less condensed chromatin than normal. In specimens from patients with HCC, most stained cancer cells were small and basophilic; electron microscopy showed indented nuclei with a few organelles and less than normal condensed chromatin. Staining showed that during regeneration, immature hepatocytes reentered the cell cycle and repaired a large necrotic area. It was conceivable that in the initiation of HCC, some small hepatocytes with indented nuclei and less condensed chromatin might become HCC cells. PMID- 2210725 TI - Quantitation of collagen fibril cross-section profiles in aging human veins. AB - The cross-section profiles and the diameter distribution of collagen fibrils were examined quantitatively in normal human internal jugular veins at different ages (first, fifth, and eighth decades). All fibrils showed a regular cross-striation pattern of native-type collagen fibrils irrespective of their cross-section profiles. Irregularly outlined ("dysplastic") fibrillar profiles were observed among the normally occurring circular cross-section profiles. The frequency of such unusual fibrils significantly increased with age. This increase was more pronounced in the tunica media as compared with the tunica adventitia. In the tunica media diameters of collagen fibrils also generally increased with age. In the tunica adventitia, on the other hand, fibrillar diameters were not significantly altered at different ages. The results of this study indicate that the frequency of both the irregularly outlined fibrillar cross-section profiles and increased fibrillar diameters depends on age in normal vascular walls. Therefore, it is concluded that the occurrence of "dysplastic" fibrils is a physiologic age-related phenomenon rather than a morphologic sign of pathologic alteration of collagen. The higher frequency of irregularly outlined collagen fibrils in the tunica media may indicate a higher and/or altered synthetic behavior of smooth muscle cells when compared with fibroblasts of the tunica adventitia. PMID- 2210726 TI - Multilobated lymphoma of B cell type: a multiparameter investigation. AB - Multilobated lymphomas were originally described as T-cell neoplasms, but many of B-cell type have subsequently been reported. A case of B-cell origin is reported in which both immunophenotypic and genotypic studies performed on a cell suspension of the lymphoma gave inconclusive and potentially misleading information, while paraffin and frozen section immunohistologic studies, as well as genotypic studies performed on DNA obtained from snap-frozen tissue, were definitive. Thus, this case illustrates some of the problems that may be encountered using cell suspensions as a source for immunophenotypic, and even the much more sensitive genotypic, studies. PMID- 2210727 TI - Polymorphic reticulosis and conventional lymphomas of the nose and upper aerodigestive tract: a clinicopathologic study of 70 cases, and immunophenotypic studies of 16 cases. AB - Seventy patients with malignant lymphomas, including the entity known as polymorphic reticulosis (PR), involving the nose, nasal sinuses, nasopharynx, oropharynx (excluding tonsil), and larynx were studied. There were 26 cases of PR, 19 cases of lymphoma with features of PR (ML[PR]) and 25 cases of conventional lymphomas. Fourteen of the 25 conventional lymphomas were due to dissemination from distant sites. For all histologic types of primary lymphoma, the presenting symptoms were similar, and the nasal cavity was more commonly involved than the nasopharynx. Patients with PR were younger, had a higher male:female ratio, and had a better overall survival rate than patients with conventional lymphomas. Cryostat section immunohistochemistry performed on 17 samples from 16 patients showed only one B lymphoma out of 11 primary lesions; the other 10 cases and three recurrent tumors at distant sites showed phenotypic markers of T lymphocytes and natural killer cells. All three secondary tumors were of B-cell type. Of eight patients with sequential biopsies, progression to a more malignant histopathologic type was found in six. In the PR and ML[PR] biopsies, angiocentricity was detected in 11%, and angioinvasion in 22%. We could not confirm identity of PR with other angiocentric immunoproliferative lesions. PMID- 2210728 TI - "Intravascular lymphomatosis" (angioendotheliomatosis): evidence for a T-cell origin in two cases. AB - Intravascular lymphomatosis (IL) is a rare and potentially fatal multifocal intravascular proliferative disorder, most often involving the skin and the central nervous system. Originally considered an endothelial disorder, IL has recently been reclassified as an angiotropic lymphoma, most often of B-cell origin. We report immunocytochemical and ultrastructural findings in two patients with IL, both representing angiotropic T-cell lymphomas. In one patient, lesional tissue was examined by Southern blot analysis and monoclonal T-cell receptor rearrangement was found. As an additional feature in one patient, a myelosuppressive serum factor was demonstrated in peripheral blood progenitor cell cultures as the cause of underlying chronic anemia and leukopenia; this factor is thought to be a cytokine product of the lymphoma cells. PMID- 2210729 TI - Germinal matrix hemorrhage of venous origin in preterm neonates. AB - The rupture point of germinal matrix hemorrhage in premature neonates was examined by postmortem angiography. Thirteen cases of germinal matrix hemorrhage were injected via artery (four cases), vein (five cases), and both artery and vein simultaneously (four cases). Only material injected via vein leaked into the hemorrhage, which was confirmed by stereomicroscopic and histologic examination. This study suggests that germinal matrix hemorrhage is venous in origin. PMID- 2210730 TI - Intercellular contacts between stromal cells in the normal human endometrium throughout the menstrual cycle. AB - Increasing differentiation in the human endometrium is associated with an apparent decrease in intercellular contacts between endometrial stromal cells PMID- 2210731 TI - Lobar atrophy with pontine neuronal chromatolysis ("ballooned" neurons). AB - A 64-year-old man developed progressive dementia over a period of 11 years. Postmortem examination showed severe atrophy of the temporal lobes of the brain with extensive neuronal loss and a remarkable alteration of the neuronal perikaryon--the "ballooned" neuron--restricted to the nuclei of the basis pontis. No neuritic plaques, neurofibrillary tangles, or Pick bodies were seen. PMID- 2210732 TI - Lymphocytic orchitis: a case report. AB - A young man with a unilateral testicular mass of short duration was found on histopathologic examination of the orchiectomy specimen to have a nongranulomatous, lymphocytic orchitis. No evidence of any infectious agent, autoimmune disease, or lymphoma could be found. We believe that this case represents an example of a nonspecific or idiopathic lymphocytic orchitis that is distinct from the hitherto recognized granulomatous orchitis. PMID- 2210733 TI - Histogenesis of the intimal thickening in atherosclerosis and of hyperplastic processes in connective tissue. PMID- 2210734 TI - Perspectives on the autopsy. PMID- 2210735 TI - Diagnostic workstations in pathology. PMID- 2210736 TI - Evaluation of a Diagnostic Encyclopedia Workstation for ovarian pathology. AB - The Diagnostic Encyclopedia Workstation (DEW) is a computer system that provides completely integrated pictorial and textual information as reference knowledge in the field of ovarian pathology. The textual component comprises information per diagnosis such as descriptions of macroscopic and microscopic images, clinical signs, and prognosis. In addition, the system offers lists of differential diagnoses and criteria to differentiate among lists of differential diagnoses and criteria to differentiate among them. The present study evaluates to what extent the system influences the diagnostic process in efficiency and outcome. Therefore, two groups of six pathologists each, covering a wide spectrum of experience in ovarian pathology, participated in the evaluation of the DEW. The quality of the resulting diagnoses was statistically analyzed with the Wilcoxon rank sum test with respect to five different viewpoints: classification, morphology, clinical consequences, duration of diagnostic process, and consensus among the participants. The results are discussed and it is concluded that classification and morphology showed better results when books were used. The evaluation experiment was, however, very rigid and negatively biased with respect to the DEW system. Positive aspects of the encyclopedia are the easy access to diagnostic and differential diagnostic information and the large set of illustrations. Insight is acquired with respect to existing bottlenecks and how they may be overcome. PMID- 2210737 TI - Computers in medical education: information and knowledge management, understanding, and learning. AB - Desktop computers have evolved to permit physicians in practice and/or training to access and manage information to enhance knowledge, understanding, and learning. There are compelling reasons why the personal computer is key to learning and important in medical education. Above all, the computer enhances and amplifies the learning process. Using the desktop computer effectively is relatively easy. We teach our students to research information in books and journals and hope that, as practicing physicians, they do it even more to be current and maintain their competency. Why not a desktop computer to access and manage information, analyze it, and present findings? Computer technology is available to do virtually all of these tasks. Some tools are critical for medical students. For some time, all medical students have needed a black bag and microscope. Now every medical student needs a computer. Ample courseware is available and expanding rapidly for basic sciences and clinical disciplines. The explosion in biomedical information will continue. Finding information is key to understanding and learning rather than depending solely on memory, recall, or library trips for information. The desktop computer will benefit students, faculty, and future physicians and other health professionals as life-long learners. PMID- 2210738 TI - Population analysis of the major mutation in cystic fibrosis. PMID- 2210739 TI - Population analysis of the major mutation in cystic fibrosis. PMID- 2210740 TI - The frequency of the CF delta F508 deletion in CF chromosomes of different ethnic origin. PMID- 2210741 TI - Cystic fibrosis in Greece: typing with DNA probes and identification of the common molecular defect. AB - The relative frequency of the delta F508 mutation in the Greek population is 54.1%; this is similar to that reported in other Southern European populations and contrasts with the considerably higher frequencies encountered in Northern Europe and North America. The low frequency is in agreement with the linkage disequilibrium already reported between cystic fibrosis and haplotype B in this country. In contrast to the common association of pancreatic insufficiency with the homozygous delta F508 genotype, the present study revealed two homozygous children with no evidence of pancreatic failure. PMID- 2210742 TI - The deletion F508 is the major gene mutation in a representative Belgian cystic fibrosis population. AB - The cystic fibrosis (CF) gene deletion F508 was studied in a Belgian population of 74 families and their 83 CF children. The haplotypes for CF and normal chromosomes had previously been determined with several linked DNA probes. In our CF population, the gene deletion F508 was found in 76% of the mutant alleles. Of the deletion F508, 97% segregated with the highest risk haplotype for the CF carrier status. Some 61% of our families were found to be homozygous for this major CF mutation. Each of our three pancreatic sufficiency patients (two of whom were siblings) was heterozygote for the F508 deletion. PMID- 2210743 TI - Distribution of the delta F508 mutation in 194 Spanish cystic fibrosis families. AB - Spanish cystic fibrosis (CF) families (n = 194) have been analysed for the delta F508 mutation, and for closely linked DNA markers. The delta F508 mutation accounts for 50% of CF chromosomes. Four haplotypes are associated with the deletion, and at least seven haplotypes carry other mutations. The second major CF mutation is associated with pancreatic insufficiency and occurred in the same haplotype in which the delta F508 arose. Only 31% of Spanish CF patients with no family history of the disease can be accurately diagnosed; about 50% of CF carriers can be detected in the Spanish population. PMID- 2210744 TI - Frequency of the major CF mutation in French CF patients. AB - We have studied 124 patients of French origin, whose CF status had already been clearly established. These children belong to families previously tested with restriction fragment length polymorphism (RFLP) markers in our laboratory for genetic counselling. The most common mutation (delta F508) accounts for 67% in this population sample. PMID- 2210745 TI - Prevalence of the delta F508 deletion of the cystic fibrosis gene in Belgian patients. AB - A sample of 107 Belgian cystic fibrosis patients has been tested for the presence of the delta F508 deletion. We have shown that 166 (78%) of the CF chromosomes presented the deletion, and that 97% of the deleted chromosomes and 50% of the non-deleted chromosomes presented the haplotype B (KM19-2/XV2c-1). PMID- 2210746 TI - Frequency of the delta F508 mutation in a sample of 175 Italian cystic fibrosis patients. AB - A sample of 175 Italian cystic fibrosis patients has been analysed for the presence of the delta F508 mutation. The frequency of this mutation among 137 patients with pancreatic insufficiency is equal to 57%; in 23 patients with pancreatic sufficiency it is 26%. A high proportion of the unknown mutations is associated with the same rare haplotype found in association with delta F508, suggesting that at least another mutation occurred on a chromosome characterized by the same haplotype. PMID- 2210747 TI - Association between XV2c/CS7/KM19/D9 haplotypes and the delta F508 mutation. A study of 57 Belgian families. AB - Using Southern blotting and the polymerase chain reaction, the prevalence of the haplotypes for XV2c, CS7, KM19 and D9 on CF and on normal chromosomes could be determined in 35 Belgian families. A set of primers complementary to the DNA sequence of the CF gene around the delta F508 deletion was used to amplify this particular segment of the gene. In a total of 57 families, deletion screening showed that 69 out of 116 CF chromosomes (59.5%) carried the delta F508 deletion. Both the delta F508 deletion and another mutation(s) showed strong association with the haplotype 1-2-2-2. PMID- 2210748 TI - Frequency of deletion 508 among Irish cystic fibrosis patients. AB - We estimate the incidence of cystic fibrosis in Ireland to be at least 1 case per 1838 live births. We have analysed DNA from 44 Irish CF patients for the presence of deletion 508, using the polymerase chain reaction. The deletion was found in 76% of their chromosomes, and approximately 58% of the patients are homozygous for this deletion. Our results are not significantly different from those found in Canadian or UK patient populations, in which frequencies are higher than those found in Southern European countries. PMID- 2210749 TI - Cystic fibrosis in the Portuguese population: haplotype distribution and molecular pathology. AB - The aim of this study was to obtain an estimate of the frequency of the delta F508 mutation in the Portuguese population, and of the tightness of its association with specific haplotypes. Furthermore, the genotype/clinical phenotype relationship and the feasibility of prenatal diagnosis were also investigated. The analysis of 42 cystic fibrosis (CF) families revealed that (1) 52% of CF chromosomes carry the deletion of codon 508; (2) there seems to be a positive correlation between the occurrence of the delta F508 mutation and the severity of the disease; and (3) fully informative prenatal diagnosis can be offered in 76% of at-risk pregnancies by using both genomic and allele specific oligonucleotide probes. PMID- 2210750 TI - The mutation delta F508 on Dutch cystic fibrosis chromosomes: frequency and relation to patients age at diagnosis. AB - We tested 190 chromosomes from Dutch cystic fibrosis (CF) patients and carriers for the presence or absence of the major CF mutation delta F508. This mutation was found on 77% of the Dutch CF chromosomes. We observed a significant difference in the distribution of the ages at diagnosis between homozygotes for delta F508 and the other patients. delta F508 homozygotes tend to be identified as patients at neonatal or infantile age. The age at diagnosis of patients with at least one unknown allele, on the other hand, ranged between neonatal and young adult age. PMID- 2210751 TI - Mutation analysis at the cystic fibrosis locus in the British population. PMID- 2210752 TI - Frequency of the F508 deletion in the CFTR gene in Turkish cystic fibrosis patients. AB - The F508 deletion in the cystic fibrosis transmembrane conductance regulator (CFTR) gene was found in 8 out of 30 Turkish cystic fibrosis (CF) chromosomes (27%). Five Turkish delta F508 CF chromosomes were associated with the risk haplotype B in KM19 (2 allele)/XV2c (1 allele). In the Turkish population, cystic fibrosis is predominantly caused by mutations other than the F508 deletion. PMID- 2210753 TI - Cystic fibrosis mutation delta F508 in Finland: other mutations predominate. AB - The frequency of mutation delta F508 was determined in all 20 Finnish cystic fibrosis (CF) families with living affected children (19 with pancreatic insufficiency). delta F508 was detected in 18 out of 40 CF chromosomes (45%). At least two different mutations associated with pancreatic insufficiently have occurred in a rare haplotype defined by XV2c, CS.7, KM19 alleles 1 2 2. Geographical clustering of delta F508 and other mutations suggested that a founder effect and genetic drift have influenced the frequency of mutations causing CF in Finland. PMID- 2210754 TI - Molecular bases for cystic fibrosis in the Sardinian population. AB - Cystic fibrosis (CF) is a relatively uncommon genetic disorder in the Sardinian population. In this study, we have defined the frequency of the most common CF mutation (delta F508) and carried out a genotype-phenotype correlation analysis in a group of 21 patients with CF and of Sardinian descent. We detected the delta F508 mutation in 24 (57%) out of the 42 CF chromosome investigated. This mutation was found in the homozygous state in 9 patients and in the heterozygous state in 6 patients. The remaining 6 patients had other mutations. The delta F508 mutation was associated only with the KM19/XV2c 2 1 haplotype. Genotype-phenotype correlation analysis did not give clear-cut results, probably because of the small number of patients investigated. However, out of the four patients with meconium ileus, three were homozygous and one was heterozygous for the delta F508 mutation, confirming that the presence of delta F508 or other severe mutations in the homozygous state is the prerequisite for the development of meconium ileus. PMID- 2210755 TI - Frequency of the delta F508 mutation and flanking marker haplotypes at the CF locus from 167 Czech families. AB - This study analyses distribution patterns of the delta F508 mutation of the cystic fibrosis transmembrane conductance regulator gene (CFTR) gene and the cystic fibrosis (CF)-linked marker loci MET, D7S23, D7S399, and D7S8 in a sample of 167 (116 complete) CF families from Bohemia and Moravia (Czechoslovakia). DNA typing was performed by polymerase chain reaction amplification, restriction analysis, and agarose or polyacrylamide gel electrophoresis. The frequency of the delta F508 mutation in this sample is 67% and the frequency of the B haplotype is 77.6% on CF chromosomes. Linkage disequilibrium was found between delta F508 and all markers tested. PMID- 2210756 TI - The haplotype distribution of the delta F508 mutation in cystic fibrosis families in Scotland. AB - The gene defective in cystic fibrosis (CF) has recently been isolated and the major mutation identified. The haplotype distribution of this mutation (delta F508) has been determined for 215 CF chromosomes in the Scottish population. delta F508 represents 73% of all CF mutations in this group. There remains considerable linkage disequilibrium between XV2c and KM19 and other mutations in the CF gene. PMID- 2210757 TI - Polymorphic DNA haplotypes and delta F508 deletion in 212 Italian CF families. AB - Haplotype data based on the DNA markers closely linked to the cystic fibrosis (CF) gene have been used to correlate the presence of the 3 bp specific deletion (delta F508) in 424 CF chromosomes from 212 Italian CF families. The distribution and the frequency of the F508 deletion on CF chromosomes in our sample suggests the presence of at least a second mutation in the same ancestral haplotype. PMID- 2210758 TI - Distribution patterns of the delta F508 mutation in the CFTR gene of CF-linked marker haplotypes in the German population. AB - We have measured the frequency of the delta F508 mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and its association with cystic fibrosis (CF)-linked marker haplotypes in the German population. Based on the analysis of 400 CF chromosomes, the frequency of the delta F508 mutation is estimated to be 77.3%, the vast majority being associated with marker haplotype KM19-XV2c 2 1. Our data further suggest the presence of another frequent CF mutation associated with this marker haplotype. PMID- 2210759 TI - Preliminary results on the frequency of the delta F508 mutation in cystic fibrosis patients from the USSR. AB - The frequency of the delta F508 mutation in a sample of 29 cystic fibrosis (CF) families from the USSR is equal to 44.8%, in agreement with previously reported haplotype data. If confirmed on a larger sample of CF patients from the USSR, this result might be indicative of the presence of a larger heterogeneity of CF mutations in the Soviet population than in other European populations. PMID- 2210760 TI - Cystic fibrosis haplotype association and the delta F508 mutation in adult British CF patients. AB - The delta F508 mutation and cystic fibrosis (CF) haplotypes with the markers KM19, pMP6d-9 and J3.11 are described in 54 adult British CF patients. delta F508 was found on 70% of all CF chromosomes, on none of the normal chromosomes and on only 37.5% of pancreatic sufficient CF chromosomes. All patients with meconium ileus were homozygous for the deletion. PMID- 2210761 TI - Frequency of the delta F508 mutation and XV2c,KM19 haplotypes in cystic fibrosis families from The Netherlands: haplotypes without delta F508 still in disequilibrium. AB - We have determined the frequency of the major cystic fibrosis (CF) three base pair deletion (delta F508) mutation in 152 CF chromosomes from patients originating from the northern part of The Netherlands. In these patients, the deletion represents approximately 76% of CF mutations. Meconium ileus is strongly associated with homozygosity for the delta F508 mutation. The XV2c,KM19 haplotypes on the CF chromosomes without the delta F508 mutation are in disequilibrium with the population frequency, although showing an increased frequency of the 1 2 haplotype. The surplus of this haplotype is almost entirely made up by the pancreatic insufficient patients. PMID- 2210762 TI - Frequency of the delta F508 mutation on cystic fibrosis chromosomes in Denmark. AB - We have investigated the frequency of the delta F508 mutation on cystic fibrosis (CF) chromosomes in Denmark. Of 304 chromosome tested, 86.8% have the delta F508 mutation. The majority of the chromosomes with this mutation are found on chromosomes with the XV2c/KM19 haplotype B (97.3%), whereas 15/16 chromosomes with haplotype C have another mutation, confirming that only very few mutations will account for the majority of CF genes in the Danish population. PMID- 2210763 TI - Delta F508 testing of the DNA bank of the Royal Manchester Children's Hospital. AB - Details of haplotype and delta F508 status from various populations represented in the cystic fibrosis (CF) DNA bank of the Royal Manchester Children's Hospital are provided, together with information on the association of genotype and clinical status. Clinical details and DNA analyses from native English in the North-West and South-West of England (Bath), from Lancashire Pakistani families and from Afrikaans Namibian families are compared. A 78.5% incidence of delta F508 has been found in English families. Compound heterozygotes with CF and only one delta F508 gene have an increased likelihood of having milder disease, with less Pseudomonas isolated from sputum and relatively more showing either no regular respiratory pathogens or colonisation with Staphylococcus. There is also a relative increase in meconium ileus in these compound heterozygotes. The diagnosis of CF may be in doubt in some subjects negative for delta F508. Some of the Bath families have unusual haplotypes for an English population and a compound heterozygote delta F508/delta I507 has been found. There is evidence from metD analysis of the founder effect in the Afrikaans Namibian families, who have a high delta F508 incidence. PMID- 2210764 TI - The delta F508 mutation in cystic fibrosis patients of southern Italy. AB - Fifty one independent cystic fibrosis (CF) families originating from a restricted area of Southern Italy (Campania) have been analyzed for KM19 and XV2c haplotypes and the delta F508 mutation: 54% of the total CF chromosomes show the delta F508 mutation. No significative correlations were obtained when clinical score, radiological score, Pseudomonas colonization, or clinical symptoms at presentation were matched with the presence or absence of the delta F508 mutation. PMID- 2210765 TI - The cystic fibrosis delta F508 mutation in the French population. AB - French families (n = 129) with at least one cystic fibrosis (CF) affected child and 44 unrelated subjects from the general population were tested for the presence of the delta F508 mutation by the polymerase chain reaction. The delta F508/CF mutation ratio (CF: uncharacterised CF mutations) was tested in the CF families with and without meconium ileus. The association between delta F508 and CF mutations and restriction fragment length polymorphism haplotypes (XV2c and KM19) has been estimated; these data suggest that the CF chromosomes include a panel of independent and probably different mutations. PMID- 2210766 TI - The incidence of delta F508 CF mutation, and associated haplotypes, in a sample of English CF families. AB - Data are presented for delta F508 screening and KM19/XV2c haplotype analysis of 195 cystic fibrosis (CF) chromosomes from the British Caucasian population. We report the frequency of delta F508 in this group to be 80% and find pronounced disequilibrium between the deletion and the KM 2, XV 1 haplotype. Haplotype analysis of 71 normal chromosomes is also presented. We report one individual who had meconium ileus and who does not have the delta F508 mutation on either chromosome. PMID- 2210767 TI - Gradient of distribution in Europe of the major CF mutation and of its associated haplotype. European Working Group on CF Genetics (EWGCFG). AB - In this collaborative European study, a total of 4871 cystic fibrosis (CF) chromosomes and 3539 normal chromosomes have been characterized for the haplotypes defined by the 2 extragenic polymorphic sequences revealed by XV2c and KM19. The association between one of these haplotypes (B haplotype) and the most frequent CF mutation, delta F508, suggests for the latter a single origin and a subsequent diffusion according to a South East-North West gradient. The linkage disequilibrium data between CF and the B haplotype in different European populations are compatible with a relatively more recent appearance of the mutation in Northern Europe whereas in Southern Europe a longer history of the same mutation would have allowed time for recombination with other haplotypes. This model is also compatible with a selective advantage of carriers but does not account for (1) the excess of B haplotypes observed among both normal and non delta F508 CF chromosomes; (2) the correlation between the B haplotype and the severity of the phenotypic effect caused by CF mutations, as measured by pancreatic insufficiency and meconium ileus. PMID- 2210768 TI - Three point mutations in the CFTR gene in French cystic fibrosis patients: identification by denaturing gradient gel electrophoresis. AB - The cystic fibrosis (CF) gene was recently identified as a gene spanning 250 kilobases (kbp) and coding for a 1480 amino acid protein, cystic fibrosis transmembrane conductance regulator (CFTR). Approximately 70% of CF mutations involve a three-base-pair deletion in CFTR exon 10, resulting in the loss of a phenylalanine at position 508 in the gene product (delta F508). In order to screen for other molecular defects, we have used a strategy based on denaturing gradient gel electrophoresis (DGGE) of polymerase chain reaction (PCR)-amplified gene segments. This method, which permits rapid detection of any sequence change in a given DNA stretch, was used successfully to analyse 61 non-delta F508 CF chromosomes from French CF patients. A study of CFTR exons 10, 11, 14a, 15 and 20 detected three mutations located in exons 14a, 15 and 20, along with several nucleotide sequence polymorphisms. These nucleotide changes were identified by direct sequencing of PCR fragments displaying altered electrophoretic behaviour, together with some of the polymorphisms and mutations previously characterized by others. The strategy presented here constitutes a valuable tool for the development of carrier testing for individuals or couples with a family history of cystic fibrosis, and will contribute to deciphering the functionally important regions of the CFTR gene. PMID- 2210770 TI - Short-term memory for numbers. AB - Each of 52 (25 female and 27 male) high school students reproduced from memory 1000 eight-digit numbers after viewing each number for 5 s. Subjects were given unlimited time to reproduce the numbers and were allowed to change their reproductions. The range of errors was very large: from 71 to 2231 out of 8000 digits reproduced by each subject. Every subject showed a serial position effect and almost the same effect--about 70% of subjects made the greatest number of errors at the seventh digit. Female subjects made significantly more errors than did the males. Every subject improved his or her score by making changes. Data are given on the relative difficulty of recalling each of the 10 digits, the 100 doublets (pairs of digits), and the 1000 triplets (sets of three digits). PMID- 2210769 TI - A 3' splice site consensus sequence mutation in the cystic fibrosis gene. AB - In the cystic fibrosis (CF) gene, recently cloned, a three base pair deletion (delta F508) has been identified in a majority of CF patients. This deletion has been found in 80% of CF chromosomes in families from north west Brittany. In order to identify new mutations we have selected 43 chromosomes negative for the three base pair deletion from these families and directly sequenced exon 11 after DNA amplification by the polymerase chain reaction. We have detected a base change (G----A) at the 3' end of the consensus sequence of intron ten (namely 1717-1). This mutation destroys a splice site in the cystic fibrosis gene which probably produces a mutant allele. This single nucleotide mutation has been reported on two other CF chromosomes. PMID- 2210771 TI - Reading from color displays: a psychophysical model. AB - We have investigated the effects of chromatic and luminance contrast on reading colored text on multicolor displays. Stimuli were defined in a color space with three cardinal axes. Two of these axes are chromatic and maximally modulate the opponent mechanisms of color vision; the third is an achromatic axis. We measured detection and discrimination of words and nonwords. The results show that near perfect reading at equiluminance is possible and that in terms of machine units, luminance differences are more salient than purely chromatic differences, but these differences disappear when the discrimination data are scaled for detection threshold. PMID- 2210772 TI - Legibility and subjective preference for color combinations in text. AB - This study examined legibility performance and subjective preference for text/background color combinations displayed on a video monitor. Luminance contrast was fixed at two preoptimized levels, either with text brighter than the background (10:1) or vice versa (1:6.5). In Experiment 1, 32 subjects rated about 800 color combinations. No evidence suggested differential effects of luminance polarity or hue, with the only exception that cool background colors (blue and bluish cyan) tended to be preferred for the light-on-dark polarity. Saturation had the most important influence on ratings. Any desaturated color combination appears to be satisfactory for text presentation. In Experiment 2 a reduced set of 18 color combinations was investigated with a new sample of 18 subjects. Reading and search times as well as multidimensional ratings were evaluated. There was no evidence for an influence of luminance polarity or chromaticity on performance. Subjective ratings corresponded well with the results of Experiment 1. PMID- 2210773 TI - Performance consequences of two types of stereo picture compression. AB - Two algorithms for stereo picture compression were evaluated. According to one algorithm, consistent with the fusion theory of depth perception, the reduction of information in the two pictures was about equal. The other algorithm, consistent with the suppression theory of depth perception, was based on very deep compression of one picture and minimal reduction of information in the second picture. Subjects performed depth decisions and object decisions on the compressed picture. They were able to perform both tasks on the compressed pictures, though performance generally was worse than in the un-compressed control conditions. In both tasks performance was better for an uneven division of information between the two pictures. These results are consistent with the suppression theory of depth perception. PMID- 2210774 TI - Work preferences as moderators of the effects of paced and unpaced work on mood and cognitive performance: a laboratory simulation of mechanized letter sorting. AB - This article describes a laboratory study of work preferences (ideal job demand and discretion levels) as moderators of the effects of paced and unpaced work on cognitive and affective responses. Posttest measures of cognitive performance and self-reported stress and arousal were used as outcome measures with covariance control for the corresponding pretest values. The experimental design allowed within-subjects contrasts of fast versus slow pacing and of machine-paced versus self-paced conditions. Self-paced performance compared favorably with machine paced performance; however, individual differences in ideal demand influenced the relative speed of work under the two conditions. Work preferences also moderated relationships between pacing and outcome measures; ideal discretion moderated machine-pacing versus self-pacing effects in relation to cognitive performance and stress, and ideal demand moderated fast versus slow pacing effects in relation to arousal. These findings are discussed in relation to existing literature on pacing and on person-environment fit. PMID- 2210775 TI - Visual mechanisms and predictors of far field visual task performance. AB - Visual mechanisms involved in target detection, recognition, and tracking were examined. Relationships were analyzed in the context of simulated combat, focusing on the short-range air defense weapon operator. Objectives were to identify visual ability interrelations, predictors of performance, and interactions with cuing, target characteristics, and experience. Good predictors included visual acuity, contrast sensitivity, resting focus, near focal point, and blur interpretation. Many of these abilities interacted with the independent variables, producing differential effects on performance. Visual abilities logically grouped into three principal components: active accommodation predicted target detection and identification; passive accommodation predicted detection and acquisition; and image interpretation predicted acquisition, identification, and tracking. Results supported the three visual subsystems hypothesis, based on neurophysiological evidence of pathways in the brain corresponding to specific visual functions. PMID- 2210776 TI - Monoclonal antibodies to complement components without the need of their prior purification. II. Antibodies to mouse C3 and C4. AB - Rat monoclonal antibodies (MAbs) to mouse complement components C3 and C4 were produced by immunizing rats with cell-bound C3 and C4. This principle involves: a) using mouse thymocytes coated with syngeneic rat antibody isotypes that show high affinity to C1q, b) the intercalation of C1q from serum and c) the subsequent activation of the classical complement pathway leading to deposition of cell-bound complement components. Screening for anti-complement antibodies was performed on antibody coating microtiter plates with mouse serum as source of complement. The reactivity of the MAbs was determined by variations of the ELISA screening system using EDTA-serum to inhibit complement activation by C1 dissociation, serum rendered deficient of functionally active C3 by treatment with cobra venom factor (CVF) or serum of genetically C5-deficient mice. The specificity of the MAbs was confirmed by affinity chromatography followed by SDS PAGE and immunoblotting. We were able to establish a panel of anti-C3 and anti-C4 MAbs of various isotypes. PMID- 2210777 TI - Markers of B lymphocyte differentiation in the chicken. AB - A study was made of the ontogeny and tissue distribution of seven antigen systems associated with B lymphocyte development. A panel of seven monoclonal antibodies (MAbs) directed against avian bursal and peripheral B lymphocytes was developed. The spectra of cellular reactivity and size of respective antigens indicate that these MAbs appear to react with determinants of chicken B lymphocytes that had not been previously described. Immunofluorescence analysis of cell surface antigens using this panel indicated that dynamic changes in antigen expression are associated with early ontogeny and maturation of the B cell lineage. The yolk sac contained subpopulations of hematopoietic cells reactive with three MAbs (CB10, CLA3 and Hy86b5) which possibly mark the pre-bursal stem cell population. At or near the time of surface IgM expression in the embryonic bursa, B cells expressed antigens detected by the CB7, CB8, CB9 and CB11. In the juvenile chicken, CB7 reacted with immature bursal lymphocytes, while CB8, CB9 and CB10 reacted with bursal lymphocytes and a subpopulation of peripheral B lymphocytes. The antigens defined by Hy86b5 and CB11 were expressed on mature B lymphocytes but on only a subpopulation of bursal lymphocytes. The MAb CLA3 detected an antigen expressed on all leukocytes but not erythroid cells. Expression of some of these antigens by cells of the myelomonocytic lineages suggests a possible functional or ontogenetic relationship between the B lymphocyte and myeloid lineages. PMID- 2210778 TI - Production of a monoclonal antibody (K 931) to a squamous cell carcinoma associated antigen identified as the 17-1A antigen. AB - During our efforts to develop monoclonal antibodies (MAbs) to tumor associated surface antigens of squamous cell carcinomas of the head and neck, monoclonal antibody K 931 was produced. The high affinity antibody (Ka 5.0 x 10(10) M-1) showed reactivity with 58 out of 62 squamous cell carcinomas of the head and neck. In contrast normal squamous epithelium as found in epidermis, oral cavity, epiglottis, pharynx, larynx and esophagus did not express the antigen. All other tested epithelial (simple and transitional) tissues did express the antigen, but non-epithelial tissues were negative. Further characterization revealed that the antigen represents the 17-1A antigen. A not earlier reported, enhanced expression of the 17-1A antigen was observed among some primary and all metastatic SCC. PMID- 2210779 TI - Production of a monoclonal antibody as immunohistochemical marker on paraffin embedded tissues using a new immunization method. AB - This report describes a method for the production of murine monoclonal antibodies (MAbs) against cellular antigens preserved during formol fixation and paraffin embedding of human tissues in an attempt to select markers that would be useful in immunopathology. Hybridomas were prepared using spleen cells from mice immunized with cell suspensions obtained from formalin-fixed paraffin block sections of a human breast carcinoma. A monoclonal antibody 83 D4 was selected, which was reactive with paraffin embedded breast carcinoma tissues, but not with normal breast. The reactive antigen has a high molecular weight (400-1000 kD) and was detected on the cell surface of live human breast cancer cell lines and on frozen tissues sections. These results demonstrate that the MAb 83 D4 identifies a native breast tumor associated epitope conserved during tissue fixation and embedding and could be used as an immunohistochemical marker. PMID- 2210780 TI - A microplate method for the determination of amino groups in monoclonal antibodies. AB - The total number of amino groups in monoclonal antibodies can be estimated via a colorimetric assay using trinitrobenzene sulfonic acid (A.F.S.A. Habeeb (1966) Anal. Biochem. 14, 328-336). This work describes the adaptation of this method to a microtiter plate in order to rapidly and reliably assay large numbers of samples. PMID- 2210782 TI - Visualization of and interaction with biomedical data. PMID- 2210781 TI - The use of syngeneic cells producing human somatotropic hormone (hSTH) for immunization of mice and development of hybridomas. AB - We studied the possibility of syngeneic cells expressing heterologous protein being used for sensitization of mice and production of hybridomas. Recombinant retroviral vector containing cloned human somatotropic hormone (hSTH) gene was used to express hSTH in BALB/3T3 cells. BALB/c mice were injected intrasplenically (i/s) or combination of intraperitoneally (i/p) and intrasplenically with hSTH-producing cells. Sensitized splenocytes were fused with myeloma cell P3X63-AgB.653. Screening for anti-hSTH hybridomas was performed by enzyme-linked immunoassay. Both single i/s injection of producer cells as well as combined i/s and i/p injections were effective for sensitization of splenocytes. Combined injection was effective for production of IgG and IgM secreting hybridomas. Single i/s injection led to generation of only IgM producing hybridomas. The results proved that syngeneic cells expressing genes of heterologous proteins can be used for splenocyte sensitization and hybridoma preparation. PMID- 2210783 TI - Visualization of multimodality cardiac imagery. AB - A large number of clinically important and medically difficult decisions in diagnostic radiology involve interpreting the information derived from multiple imaging modalities. This is especially true in the assessment of heart disease, wherein at least two types of image information are generally required prior to deciding on the course of action: structural information describing coronary vessel anatomy and functional information related to heart muscle physiology. This paper will present and discuss the methods and results associated with a research program aimed at quantifying and visualizing the unified anatomic and physiologic information obtained from these complementary imaging modalities. The discussions will emphasize the reconstruction, processing, and visualization of three-dimensional cardiovascular structure, including the procedures and results obtained from phantom and patient studies. PMID- 2210784 TI - An interactive graphics-based model of the lower extremity to study orthopaedic surgical procedures. AB - We have developed a model of the human lower extremity to study how surgical changes in musculoskeletal geometry and musculotendon parameters affect muscle force and its moment about the joints. The lines of action of 43 musculotendon actuators were defined based on their anatomical relationships to three dimensional bone surface representations. A model for each actuator was formulated to compute its isometric force-length relation. The kinematics of the lower extremity were defined by modeling the hip, knee, ankle, subtalar, and metatarsophalangeal joints. Thus, the force and joint moment that each musculotendon actuator develops can be computed for any body position. The joint moments calculated with the model compare well with experimentally measured isometric joint moments. We developed a graphical interface to the model that allows the user to visualize the musculoskeletal geometry and to manipulate the model parameters to study the biomechanical consequences of orthopaedic surgical procedures. For example, tendon transfer and lengthening procedures can be simulated by adjusting the model parameters according to various surgical techniques. Results of the simulated surgeries can be analyzed quickly in terms of postsurgery muscle forces and other biomechanical variables. Just as interactive graphics have enhanced engineering design and analysis, we have found that graphics-based musculoskeletal models are effective tools for designing and analyzing surgical procedures. PMID- 2210785 TI - Three-dimensional quantitative coronary angiography. AB - A method for reconstructing the three-dimensional coronary arterial tree structure from biplane two-dimensional angiographic images is presented. This method exploits the geometrical mathematics of X-ray imaging and the tracking of leading edges of injected contrast material into each vessel for identification of corresponding points on two images taken from orthogonal views. Accurate spatial position and dimension of each vessel in three-dimensional space can be obtained by this reconstruction procedure. The reconstructed arterial configuration is displayed as a shaded surface model, which can be viewed from various angles. Such three-dimensional vascular information provides accurate and reproducible measurements of vascular morphology and function. Flow measurements are obtained by tracking the leading edge of contrast material down the three dimensional arterial tree. A quantitative analysis of coronary stenosis based on transverse area narrowing and regional blood flow, including the effect of vasoactive drugs, is described. Reconstruction experiments on actual angiographic images of the human coronary artery yield encouraging results toward a realization of computer-assisted three-dimensional quantitative angiography. PMID- 2210786 TI - Segmentation of coronary arteriograms by iterative ternary classification. AB - A segmentation algorithm for extracting arterial structures in coronary angiograms is presented. The algorithm mimics the process of interactive interpretation in human vision by iteratively implementing a ternary classification and learning process. Two gray-scale thresholds are computed to define three pixel classes: artery, background, and undecided. Then, two new thresholds for undecided pixels are computed using statistics conditioned upon the current classification. The threshold adaptation is governed by a learning algorithm based on the line and consistency measurements around each pixel. The process converges and results in a binary image. The performance of this algorithm on human coronary arteriograms was compared qualitatively to that of a relaxation algorithm and of a scattering based algorithm. Quantitative comparison was also made possible with computer generated images, which were obtained with the help of a model of the imaging chain and a process of interactive visualization of the modeled data. The iterative ternary classifier showed the best performance over a broad range of image quality. The study also demonstrated the use of visualization and user interaction in model building and algorithm development. PMID- 2210787 TI - Visualization of dynamic subcutaneous vasomotor response by computer-assisted thermography. AB - Infrared thermography is a noninvasive and nonionizing imaging modality which detects thermally significant subcutaneous blood vessels as linear heat patterns projected onto the skin surface. In clinical thermography, pseudo-colors are typically used to represent isothermal regions. However, pseudo-colors destroy the connectivity of vascular patterns since the intravenous temperature of a subcutaneous blood vessel varies along its length. This representation also confounds estimates of vessel boundary location since boundary information is rendered by temperature gradients, and not by isotherms. This paper describes two computer-assisted methodologies for the visualization of peripheral subcutaneous vasomotor events. The first approach, which utilizes a three-stage segmentation strategy based on edge detection, can visualize temperature differences of approximately 3.5 degrees C between the subcutaneous vessel boundaries and surrounding tissue. The second approach requires user interaction with an adaptive filtering algorithm that selectively enhances vascular patterns in the thermogram while decreasing background noise artifacts. The user interactively selects decision thresholds used by the algorithm to develop symbolic, axiomatic models of homogeneous and bimodal local contrast regions. The result of this trained filter is then employed in a technique called digital subtraction thermographic venography for the extraction of subcutaneous venous patterns. This second approach shows less ambiguity and higher sensitivity than the edge detection approach in resolving subtle temperature differences of approximately 1.2 degrees C between the vessel and surrounding tissue. Computer-processed frames from both of these approaches are used for the dynamic visualization of normal and pathological vasomotor responses to thermal challenges, thereby providing diagnostic visual cues which are unavailable in the original thermograms. PMID- 2210788 TI - A workstation-based system for 2-D echocardiography visualization and image processing. AB - Parameters of cardiac function can be drawn from the analysis of echocardiographic image sequences, especially the motion of the ventricular wall, heart wall thickness, and shape parameters. Automatic image analysis and visualization allows reduced manual operations and, above all, ensures objectivity and repetition of analysis, which is essential when one wishes to calculate parameters based on variations, i.e., on image sequence analysis. In this paper, a system and the related software package for interactive echocardiographic image analysis and visualization are illustrated and discussed. Furthermore, the full model for smoothing, edge enhancement, and contour detection is discussed and a new technique based on the heat anisotropic diffusion model is presented. The results of automatic detection of the left ventricle contours are presented and discussed. PMID- 2210789 TI - TDAT--time domain analysis tool for EEG analysis. AB - An interactive design and analysis tool for displaying and quantifying multiple channels of data is presented. The system allows one to easily visualize multiple data channels and simultaneously observe the effects of filters on the data and to evaluate signal detection algorithms. The software is designed for a workstation environment; it will find application in a variety of applications where one needs to simultaneously visualize multiple data channels. TDAT is being used for the design and evaluation of filters and detection algorithms for electroencephalogram (EEG) waveforms, and it is serving as a prototype of a paperless system to be used by electroencephalographers. This paper describes the general software structure of the system and illustrates many of the system features with examples. PMID- 2210790 TI - A computer-aided movement analysis system. AB - Interaction with biomechanical data concerning human movement analysis implies the adoption of various experimental equipments and the choice of suitable models, data processing, and graphical data restitution techniques. The integration of measurement setups with the associated experimental protocols and the relative software procedures constitutes a computer-aided movement analysis (CAMA) system. In the present paper such integration is mapped onto the causes that limit the clinical acceptance of movement analysis methods. The structure of the system is presented. A specific CAMA system devoted to posture analysis is described in order to show the attainable features. Scientific results obtained with the support of the described system are also reported. PMID- 2210791 TI - [Chronic inflammatory intestinal diseases]. PMID- 2210792 TI - [Changes in the immune system of the gastrointestinal tract in Crohn disease]. AB - In Crohn's disease and ulcerative colitis various alterations in the immune system have been reported. In this paper changes in the peripheral as well as in the mucosal immune system are summarized and critically analyzed. PMID- 2210793 TI - [The role of arachidonic acid metabolism in the pathophysiology of chronic inflammatory intestinal diseases]. AB - Crohn's disease and ulcerative colitis are chronic inflammatory diseases of the bowel with unknown etiology. Alterations of intestinal and systemic immuno regulation are probably of importance in the pathophysiology of both diseases. Moreover, recent studies suggest that polymorphonuclear granulocytes and probably macrophages are of particular importance in the initiation of an acute flare of the disease. Interest has therefore focused on arachidonic acid metabolites, in particular leukotrienes and prostaglandins, which are important mediators in granulocyte and macrophage activation and chemotaxis. The pathophysiologic importance of various leukotriene derivatives, particularly LTB4, has been well established whereas the actions of prostaglandins in vivo, in particular PGE2, are controversial. Numerous anti-inflammatory drugs such as glucocorticoids and salicylic acid derivatives have been successfully used to treat intestinal inflammation. One possible mechanism of action is the modulation of arachidonic acid metabolism and thus regulation of the genesis of active inflammatory mediators. PMID- 2210794 TI - [Drug therapy of chronic inflammatory intestinal diseases]. AB - The therapy of inflammatory bowel diseases (Crohn's disease, ulcerative colitis) has been improved in recent years. This is mainly due to our better understanding of application of aminosalicylates and steroids in regard to localization, activity, and type of chronic inflammatory bowel disease. Newly developed aminosalicylates like mesalazine provoke less side effects. Furthermore, they seem to be effective in the treatment of ileal inflammation of Crohn's disease. Therapy with immunosuppressive drugs like mercaptopurine, azathioprine, and cyclosporin A is justified in case of steroid-resistant Crohn's disease. Alternative therapeutic concepts are at present at the stage of clinical trial. PMID- 2210795 TI - [Therapy of hayfever and pollen asthma in children with a new, modified allergen extract]. AB - During a period of 3 years a controlled and prospective study was performed, in which 20 children with pollinosis and pollen asthma (grass pollen) were treated either with a new modified allergenic extract (preparation I: Purethal) or with a standard semi-depot extract (preparation II: Depot-HAL) from the same producer. During the pollen season symptoms, side effects, additional medication, and pollen counts were registered. 20 patients were treated perennially: 5 with preparation II and with reduction of the doses during the pollen season (group A: treatment during 3 successive years), 15 without reduction of the doses during te season with preparation I (group B, 8 patients: treatment during 3 successive years; group C, 7 patients: treatment during 2 successive years). Patients in all groups showed more symptoms in May and June. In the groups B and C less symptoms were recorded. Especially, the score of asthma symptoms decreased. However, the need for additional medication was somewhat higher in these groups as compared to group A. The differences were not statistically significant. In 50% of the children no local side reactions were observed after the subcutaneous injections. In the groups B and C the number of late local reactions after 6 to 8 hours was somewhat higher. The patients treated with preparation I did not show an increase of allergen-specific IgG during the pollen season. The relative contribution of allergen-specific IgG1 and IgG4 to total specific IgG was lower in the blood samples of these patients as compared to those of group A. The efficacy and the therapeutic safety of the two preparations are comparable. Preparation I has a number of practical advantages, especially in the treatment of children. PMID- 2210796 TI - [Thrombocyte growth factor]. AB - PDGF is one of the principal mitogens for cultured cells of mesenchymal origin. Apart from aggregated platelets PDGF can be secreted by a number of cells. There is a striking homology between the amino-acid sequence of PDGF and that of a transforming protein of simian-sarcoma virus. PDGF is an important chemotactic protein for cells implicated in wound healing. Furthermore, recent publications suggest a possible role in the pathogenesis of several diseases. This article summarizes studies and recent findings on the structure, biology, and functional role of PDGF. PMID- 2210797 TI - 21st meeting of the Society of Immunology. September 12-16, 1990, Aachen, Federal Republic of Germany. Abstracts. PMID- 2210799 TI - Demonstration of MHC class II-restricted cytotoxic T lymphocytes in mice against herpes simplex virus. AB - In humans CD4+ major histocompatibility complex (MHC) class II-restricted T cells dominate cytotoxic T-lymphocyte (CTL) responses to herpes simplex virus (HSV), whereas in the mouse only CD8+ MHC class I-restricted CTL have been reported. In this study, we demonstrate that a minor fraction (around 30%) of the response in draining lymph nodes of acute local HSV infections is attributable to CD4+ CTL mice. Such CTL were identified on the basis of antiserum inhibition studies, negative depletion approaches, as well as their differing antigen processing requirements to CD8+ MHC class I-restricted CTL. A possible role for CD4+ CTL as immunoregulators in local infections is discussed briefly. PMID- 2210798 TI - Differences in affinity of anti-CD4 monoclonal antibodies predict their effects on syncytium induction by human immunodeficiency virus. AB - A panel of 20 anti-CD4 monoclonal antibodies (mAb) was ranked in terms of affinity, using an inhibition radioimmunoassay. The ability of these antibodies to inhibit the induction of syncytia by human immunodeficiency virus (HIV) and to prevent binding of the HIV envelope glycoprotein 120 (gp120) to CD4 was also measured. Syncytium inhibition correlated strongly with affinity (P less than 0.001) but only weakly with inhibition of gp120 binding (P = 0.038). Some antibodies partially blocked binding of gp120 to CD4 but did not inhibit syncytia, and some antibodies inhibited syncytia but only weakly blocked binding of gp120. These results suggest that the syncytium inhibition assay is highly affinity-dependent, and that epitopes on CD4 concerned with virus binding are distinct from those involved in syncytium formation. PMID- 2210800 TI - Immunization of guinea-pigs against Rhipicephalus appendiculatus adult ticks using homogenates from unfed immature ticks. AB - Guinea-pigs immunized with homogenates of unfed larvae and nymphs of the tick Rhipicephalus appendiculatus developed significant levels of protective immunity to infestation with adults of this species. The mean engorged weight of female ticks feeding on immunized animals (181.96 +/- 05.63 mg and 170.11 +/- 11.54 mg) was reduced by an average of 46% and 51%, respectively, compared to that of female ticks feeding on control guinea-pigs, although in some individual animals the reduction was as high as 86%; the mean egg mass weight was also significantly reduced. Electrophoretic separation of the homogenates followed by immunostaining with post-infestation sera revealed several antigen bands common to all stages. Two bands of 36,500 and 23,000 molecular weight (MW) were recognized in all homogenates by post-adult infestation serum, but not by post-larval or post nymphal infestation sera, suggesting that these may be antigens specifically involved in feeding by adult ticks, and are either not presented to the host's immune system or presented only in minimal amounts during feeding by immature stages. Sera from animals immunized with the homogenates did not recognize either of these antigens. Post-immunization sera did, however, stain two bands of 84,000 and 60,000 MW in the homogenates which were not recognized by post-infestation sera. PMID- 2210801 TI - Generation of lymphokine-activated killer cells in long-term cultures. AB - The induction of lymphokine-activated killer (LAK) cells with low levels of interleukin-2 (IL-2) was studied in long-term cultures with regard to the relationship between cytotoxicity and proliferation. Proliferation of LAK cells reduced their cytolytic activity, which was restored when proliferation stagnated. In order to explain this phenomenon, a competition between receptors of intermediate and high affinity for IL-2 is suggested. Whereas the former type of receptor mediates cytotoxicity, the second one seems to be responsible exclusively for proliferation of LAK cells. PMID- 2210802 TI - IL-3 and IL-4 affect thymocyte differentiation in organ culture. AB - The ability of lymphokines to affect the development and differentiation of mouse thymocytes in vitro was evaluated in a carefully controlled 3-day organ culture system. Concanavalin A (Con A)-induced supernatant (SN) from the T-cell clone D10.G4, which contains high concentrations of interleukin-3 (IL-3), IL-4 and IL 5, but lacks IL-1, IL-2 and interferon (IFN), markedly increased the proportion of CD4+CD8- cells, and decreased the proportion of CD4+CD8+ cells. These effects were unaffected by dialysing the SN, showing them to be caused by macromolecular factors. Highly purified recombinant IL-3 and IL-4 could exert similar effects, rIL-3 and rIL-4 both increasing the proportion of CD4+CD8- cells, and rIL4 in addition reducing the proportion of CD4+CD8+ cells. In conjunction with the findings of other investigators, these results indicate that at least four lymphokines (IL-1, IL-2, IL-3 and IL-4) can control T-cell development in the thymus. PMID- 2210803 TI - Targeting of human cytotoxic T lymphocytes to MHC class II-expressing cells by staphylococcal enterotoxins. AB - The staphylococcal enterotoxins (SE) comprise a family of structurally related phage-encoded bacterial proteins, which are the most potent mitogens known for murine and human T lymphocytes. In this report we describe a novel cytotoxic mechanism, where SE directs human CD3+ T lymphocytes to mediate strong cytotoxicity against target cells of irrelevant nominal specificity. The SE dependent cellular cytotoxicity (SDCC) occurred at picomolar concentrations of SE and involved the initial binding of the SE to the target cells and subsequent triggering of the cytotoxic T cells. SDCC was induced by SEA, SEB, SEC1 and SED, which indicates that this is a common property conserved among all SE. Certain antibodies to the HLA-DR molecule efficiently blocked SDCC. Major histocompatibility complex (MHC) class II+ RAJI cells and HLA-DR-transfected murine L cells were sensitive to SDCC, whereas the MHC class II- RJ.2.2.5 RAJI cell mutant and untransfected L cells were completely resistant to SDCC. These results demonstrate that the MHC class II antigen is the target molecule in SDCC. HLA-DR molecules acted as receptors for SE and the complex was recognized by T lymphocytes in a polyclonal fashion. SDCC was mediated by allospecific cytotoxic CD8+ T cells, by cloned CD8+ T cells and by fresh human peripheral blood mononuclear cells. The SDCC phenomenon provides a rapid, potent and specific mechanism for elimination of HLA-DR+ target cells. We suggest that SDCC is an important combat strategy, employed by the bacteria to avoid specific MHC class II antigen-dependent immune recognition, by inducing T-cell dependent autologous lysis of MHC class II-expressing cells. PMID- 2210804 TI - Effects of induced anemia in normal and autoimmune mice. AB - Normal and autoimmune mice were studied with regard to signals eliciting differentiation and division of bone marrow stem cells. The erythropoiesis induced by anemia following serial bleedings was analyzed in young autoimmune New Zealand Black (NZB) mice and non-autoimmune strains. No difference in the response to the stimulus created by anemia was noted between the strains. After serial bleedings as a stimulus to stem cell proliferation, a five-fold increase in numbers of proliferating spleen cells occurred in both NZB and DBA/2 strains; the increased proliferating spleen cells in both strains were non-lymphoid. The bled animals had decreased percentages of B cells. The production of autoantibodies was not significantly altered by the experimentally induced anemia. In contrast, anti-immunoglobulin activation of resting B cells was increased in response to anemia. Young mice which had experimentally induced anemia had several characteristics in common with old autoimmune NZB mice. Both old NZB mice and young anemic animals had splenomegaly, increased numbers of proliferating spleen cells, decrease in splenic Ly 5+ cells and an increase in splenic colony forming units (CFUs). The anemic normal strains of animals lacked other characteristics of old NZB mice such as hyperimmunoglobulinemia or autoantibody production or elevated CD5+B cell numbers. This work supports the concept that the increase in spleen cell number, proliferating spleen cells, CFUs and the increased percentages of non-Ly-5 cells (which include erythroid precursors) found in the spleens of old NZB mice may in part result from their autoimmune hemolytic anemia. PMID- 2210805 TI - A simple procedure for isolation of tumor-associated antigens by affinity chromatography using fucose-specific Aleuria aurantia lectin. AB - An affinity column containing L-fucose specific Aleuria aurantia lectin was used for the efficient separation of tumor-associated antigens. Five of six glycoconjugates antigens tested, carcinoembryonic antigen (CEA), CA19-9, sialyl Lewis X-i, DU-PAN-2 and CA125, bound to the affinity gel and eluted in high yield with 20 mM L-fucose, but alpha-fetoprotein, which is known to contain fucose in the carbohydrate chain, passed through the column. This column was also proved to be useful for group separation of CA19-9, sialyl Lewis X-i and Leb antigens from a serum sample with gastric cancer. PMID- 2210806 TI - Time course of hemodynamic responses to sodium in elderly hypertensive patients. AB - Thirty-one patients with essential hypertension (81.6 +/- 6.9 years old) were studied during two different regimens of sodium intake: 120 meq/day for 8 weeks and 344 meq/day for 2 weeks. Systemic hemodynamic data were measured with Doppler echocardiography from which the mitral flow velocity integral, cardiac index, and total peripheral resistance were calculated. The salt-sensitive patients in whom the increase in total peripheral resistance was greater than the increase in cardiac index with salt loading were termed SST. In the salt-sensitive patients termed SSC, the increase in cardiac index was greater than the increase in total peripheral resistance with increased sodium intake. All SST patients on day 7 of the high sodium diet remained in the SST group on day 14. Nine of 13 patients in the SSC group on day 7 remained in the SSC group on day 14, and the remaining four patients in the SSC group on day 7 fell into the SST group on day 14. Four of eight non-salt-sensitive (NSS) patients on day 7 of the high salt regimen remained in the NSS group on day 14, whereas the remaining four patients in the NSS group on day 7 fell into the SSC group on day 14. Our data suggest a changing pattern with sodium loading of initially high cardiac index followed by a persistently raised total peripheral resistance. The celiac, superior mesenteric, and renal arteries vasoconstricted with sodium repletion in both SST and SSC patients. With salt loading, the terminal aortic vascular bed vasodilated in the SSC patients and vasoconstricted in the SST patients. PMID- 2210807 TI - Two-way factorial study of alcohol and salt restriction in treated hypertensive men. AB - The aim of this study was to determine whether moderate restriction of dietary salt intake leads to an additional fall in blood pressure in treated hypertensive men who are asked to simultaneously reduce their usual alcohol intake. Sixty three subjects entered an initial 2-week familiarization period during which they continued their usual alcohol intake and commenced a "low sodium" diet (less than 60 mmol/day) supplemented with 100 mmol sodium chloride per day as enteric-coated tablets. Subjects were then randomly assigned to either drink a low alcohol beer alone for a 4-week period (reducing their self-reported alcohol consumption from 537 to 57 ml/week) or to continue their usual alcohol intake (543 versus 557 ml/week). Within the low and normal alcohol intake groups, subjects were assigned to either a low or normal sodium intake. The low sodium groups continued the sodium-restricted diet but were switched to placebo sodium chloride tablets for the 4 weeks. This resulted in a fall in the 24-hour urinary sodium excretion from 144 to 69 mmol/day. The normal sodium groups continued the low sodium diet but kept taking 100 mmol/day of the sodium chloride tablets, and their urinary sodium excretion remained unchanged (125 versus 142 mmol/day). Regular antihypertensive therapy was continued throughout. Fifty-nine subjects completed the trial. In those who reduced their alcohol intake there was a fall in both systolic blood pressure (-5.4 mm Hg supine, p less than 0.01) and diastolic blood pressure (-3.2 mm Hg supine, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210808 TI - Salt sensitivity in humans is associated with abnormal acid-base regulation. AB - Metabolic acidosis has recently been observed in rat models of salt-sensitive genetic hypertension. To test the hypothesis that salt sensitivity in humans may be associated with abnormal acid-base homeostasis, we performed arterial blood gas analyses in young (20-31 years old) normotensive subjects (n = 40) who were placed on a low salt diet (20 mmol NaCl/day) for 2 weeks with either 200 mmol sodium chloride or placebo added to the low salt diet for 1 week each in a randomized, single-blind crossover order. Furthermore, a subset of the subjects (seven salt-sensitive and eight salt-resistant) received 200 mmol sodium/day as the citrate salt as a supplement to the low salt diet for a third week. During each regimen, blood pressure as well as arterial pH and bicarbonate levels were measured. Salt sensitivity was defined as a significant drop in mean arterial pressure greater than 3 mm Hg (mean of 30 readings taken during each diet, p less than 0.05) while the subject was on the low salt diet. According to this definition, 16 subjects were salt-sensitive and 24 salt-resistant. During the high sodium chloride regimen, arterial pH and bicarbonate levels were significantly lower in the salt-sensitive than in the salt-resistant group (p less than 0.0001). The increase in blood pressure caused by sodium chloride correlated inversely to the arterial pH (r = -0.57, p = 0.0002) and bicarbonate levels (r = -0.52, p = 0.0007) during the high salt diet. Sodium chloride increased mean arterial blood pressure in the salt-sensitive subjects; sodium citrate did not. Sodium citrate led to an increase in pH and bicarbonate levels in both groups. Our finding that a sodium chloride-induced rise in blood pressure is associated with lower arterial plasma pH and bicarbonate levels points to an abnormality in renal acid-base regulation in salt-sensitive subjects. PMID- 2210809 TI - Sequential spectral analysis of 24-hour blood pressure and pulse interval in humans. AB - Blood pressure and pulse interval are characterized not only by erratic variations but also by rhythmic fluctuations at low-, mid-, and high-frequency (0.025-0.07, 0.07-0.14, and 0.14-0.35 Hz, respectively). However, information on these phenomena has largely been derived from analysis of short-term recordings taken in standardized laboratory conditions. In seven normotensive and 10 untreated mild essential hypertensive subjects, power spectrum analysis was performed on the intra-arterial blood pressure and pulse interval signal collected over a 24-hour period using the fast Fourier transform algorithm and splitting the recording into contiguous segments of 256 beats. About 70% of the segments were suitable for the analysis; the segments excluded for a nonstationary signal amounted to only 30%. All powers were characterized by a high segment-to-segment variability, but in each subject the mid- and high frequency powers of diastolic blood pressure and the mid-frequency power of systolic blood pressure were markedly reduced during the night as compared with the daytime period, whereas the opposite occurred for the low- and high-frequency powers of the pulse interval. Over the 24-hour period, mid- and high-frequency powers of blood pressure were positively correlated to each other, but both accounted for less than 25% of the 24-hour blood pressure variance. No difference between mean normalized power values of normotensive and hypertensive subjects was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210810 TI - Diurnal cardiovascular patterns in spontaneously hypertensive and Wistar-Kyoto rats. AB - This study was designed to determine whether diurnal patterns of blood pressure, heart rate, or locomotor activity differed among two substrains of Wistar-Kyoto rats, derived originally from Charles River or Taconic Farms stock, or the spontaneously hypertensive rat. Cardiovascular parameters were continuously monitored over 24 hours. Resting systolic and diastolic blood pressure values were statistically different among the three groups both during the lights-on (rest) and lights-off (active) phases of the cycle with blood pressure of spontaneously hypertensive rats greater than that of Wistar-Kyoto rats from Taconic Farms, which was greater than that of Wistar-Kyoto rats from Charles River. The largest difference in arterial pressure between Wistar-Kyoto/Taconic Farms and Wistar-Kyoto/Charles River was during the lights-on period. Heart rates of all rats decreased during the lights-on period; Wistar-Kyoto/Charles River had the largest decrease (-70 +/- 5 beats/min), Wistar-Kyoto/Taconic Farms had the least (-17 +/- 2 beats/min), and in spontaneously hypertensive rats the decrease was intermediate (-29 +/- 3 beats/min). The pronounced diurnal variation in pressure and heart rate exhibited by Wistar-Kyoto/Charles River was not present in either Wistar-Kyoto/Taconic Farms or spontaneously hypertensive rats. Blood pressure magnitude correlated with locomotor activity during both periods, although all groups showed minimal activity during the rest period. Observed differences between Wistar-Kyoto/Charles River and Wistar-Kyoto/Taconic Farms were not due to a lack of or an abnormality in baroreceptor reflex function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210811 TI - A kallikrein-like enzyme in blood vessels of one-kidney, one clip hypertensive rats. AB - Active and inactive kallikrein or a kallikrein-like enzyme are found in the aorta, vena cava, and tail artery and veins of the rat. We studied the concentration of vascular kininogenase in rats with one-kidney, one clip renovascular hypertension and in unilaterally nephrectomized normotensive rats. Six weeks after surgery, active and total vascular kininogenase activity (active plus trypsin-activated) was measured. Blood pressure was 212 +/- 4 mm Hg in the hypertensive rats (n = 33) and 120 +/- 1 mm Hg in the normotensive rats (n = 32) (p less than 0.001). Active kininogenase was lower in the hypertensive rats; although the difference was not significant in the thoracic aorta (56 +/- 8 versus 77 +/- 15), it was highly significant in the abdominal aorta (63 +/- 13 versus 167 +/- 17, p less than 0.001) and tail artery (48 +/- 8 versus 197 +/- 31, p less than 0.003). Total vascular kininogenase activity (active plus trypsin activated) was lower in the hypertensive rats in all arteries examined: thoracic aorta (183 +/- 16 versus 380 +/- 38, p less than 0.003), abdominal aorta (565 +/- 61 versus 1,093 +/- 74, p less than 0.001), and tail artery (532 +/- 112 versus 1,243 +/- 135, p less than 0.003). Active kininogenase in the vena cava was higher in the hypertensive rats (213 +/- 56 versus 131 +/- 31); however, this difference was not statistically significant, whereas in the tail veins it was highly significant (1,803 +/- 221 versus 771 +/- 79, p less than 0.003).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210812 TI - Development of hypertension from unilateral renal artery stenosis in conscious dogs. AB - The renal and systemic changes after stenosis of the left renal artery (n = 5) or sham stenosis (n = 6) in conscious dogs were studied sequentially over 25 days. Stenosis produced a prompt rise in arterial pressure, which was at all times due to reduced peripheral vascular conductance, with no increase in cardiac output despite initial evidence of mild fluid retention. The decrease in peripheral conductance was attributable to 1) the stenotic kidney (25% of the total and due to the mechanical effect of the stenosis itself), 2) the nonstenotic kidney (about 15% of the total and not caused by angiotensin II), and 3) the nonrenal vasculature (60%). The decrease in conductance in the nonrenal vasculature was due partly to angiotensin II, but there was also a gradually developing non angiotensin II component. Acute administration of captopril caused significantly greater changes in arterial pressure and peripheral conductance throughout the period of stenosis than before stenosis (and greater than in sham-stenosis dogs), indicating that angiotensin II was constricting the peripheral vasculature even when plasma renin levels were no longer elevated. In the stenotic kidneys, captopril produced a fall in renal vascular resistance, but renal blood flow did not rise because there was an approximately equal rise in the resistance of the stenosis. There was no evidence for a role for the autonomic nervous system in the hypertension, as ganglion blockade (pentolinium) had similar hemodynamic effects before and after stenosis. Thus, the hypertension was due at all times to reduced peripheral conductance, with the two kidneys responsible for 40% of this reduced conductance. PMID- 2210813 TI - Comparison of converting enzyme inhibitor and calcium channel blocker in hypertensive glomerular injury. AB - The protective effect of converting enzyme inhibitors in experimental hypertensive glomerular injury is associated with decreased systemic arterial and glomerular capillary pressure. Although calcium channel blockers effectively lower systemic blood pressure, their effect on glomerular capillary pressure and on hypertensive glomerular injury is uncertain. We compared equihypotensive treatment with the calcium antagonist TA 3090 or the converting enzyme inhibitor captopril in post-salt hypertensive Dahl salt-sensitive (DS) rats for up to 5 weeks after five sixths nephrectomy. Before the nephrectomy, all rats demonstrated hypertension (mean 177 mm Hg), proteinuria (mean 175 mg/day), and mild glomerulosclerosis (mean injury score 35). Rats treated with captopril or TA 3090 demonstrated a significant and equivalent decrease in systolic blood pressure compared with untreated rats at 2, 3, and 5 weeks after five sixths nephrectomy; however, only captopril reduced proteinuria. Final proteinuria was actually increased in rats treated with TA 3090 compared with untreated rats. Glomerular injury score was significantly decreased in captopril-treated compared with untreated rats at 2 weeks (33 +/- 9 versus 117 +/- 10, p less than 0.05) and 5 weeks (46 +/- 9 versus 94 +/- 24, p less than 0.05), whereas treatment with TA 3090 delayed but did not prevent progressive glomerular injury (2-week score 35 +/- 7, p less than 0.05 versus untreated; 5-week score 109 +/- 19, p = NS versus untreated). Thus, in hypertensive DS rats after subtotal nephrectomy, treatment with a converting enzyme inhibitor reduced systemic blood pressure, proteinuria, and glomerulosclerosis. However, equihypotensive treatment with a calcium channel blocker did not reduce proteinuria and delayed but did not prevent glomerulosclerosis. Thus, in the rat similar reductions in systemic blood pressure with these two classes of agents have disparate effects on the progression of chronic renal failure. PMID- 2210814 TI - Interleukin-2 does not attenuate hypertension in spontaneously hypertensive rats. AB - It was recently reported that interleukin-2, when administered as a single bolus injection (5,000 units/kg), could prevent the development of hypertension in young spontaneously hypertensive rats and lower blood pressure to normotensive levels in spontaneously hypertensive rats with established hypertension. Consequently, efforts were made to duplicate this finding. Male spontaneously hypertensive rats (35 days old) were injected subcutaneously with 50,000 units/kg (3,500 units/rat) of recombinant interleukin-2 (Amgen) and had systolic blood pressure measured twice weekly by the tail-cuff technique. Systolic blood pressure in the interleukin-2-treated group was not significantly different from the vehicle-treated control group at any time point over 32 days of follow-up. A second injection of recombinant interleukin-2 (5,000 units/kg) was administered 32 days after the first injection. Again, no reduction in blood pressure was observed in the interleukin-2-treated group over an additional 38 days. Mean arterial pressure (+/- SEM) measured via intra-arterial cannula in conscious rats at age 105 days (38 days after the second treatment) was 168.5 +/- 3.5 mm Hg in interleukin-2-treated spontaneously hypertensive rats and 170.3 +/- 3.6 mm Hg in vehicle-treated controls. Both recombinant interleukin-2 preparations conformed to their respective manufacturer's indicated specific activity as determined by the ability of the interleukin-2 to induce proliferation of the interleukin-2 dependent cell line HT-2. Thus, this study demonstrated that interleukin-2 was ineffective in preventing or attenuating hypertension in spontaneously hypertensive rats. PMID- 2210815 TI - Reminiscences of the Veterans Administration trial of the treatment of hypertension. PMID- 2210816 TI - Childhood risk factors for adult hypertension. PMID- 2210817 TI - A feasible strategy for a health care package. PMID- 2210818 TI - Childhood obesity and hypertension. AB - Using the criteria of weight(g)/height(cm)2 greater than or equal to 2.26 as cut off point, 292 (7.56%) of the 3,861 school children in the age group 5-15 years were identified as obese. The mean blood pressure levels, both systolic and diastolic, were found to be significantly higher in the obese subjects compared to the controls (p less than 0.001). Further, 10 (3.4%) of the 292 obese subjects were detected to have sustained elevations in BP levels (BP greater than mean + 2 SD for age-sex) on monthly follow-up for 6 months. On the contrary, persistent hypertension was detected in only six (0.16%) of the 3,569 controls. None of these hypertensive children had any symptoms attributable to raised blood pressures and all had only mild elevations in BP levels. Baseline investigations, carried out in 9/16 subjects, failed to document any underlying cause for hypertension. Serum cholesterol levels, however, were elevated in six subjects. This suggests a close association between childhood obesity and essential hypertension. PMID- 2210819 TI - Sex bias in immunization coverage in an urban area of U.P. AB - Two hundred and ten female and two hundred and ten male children aged 1-2 years were identified using 30 cluster random sampling technique in the Nagar Palika of Sitapur. The immunization status was determined to assess differences, if any, in the coverage in accordance with the sex of the child. Except for measles, a significantly higher vaccination coverage was observed for male children as compared to females for every vaccine, this being 65.2 and 60.9%, respectively for DPT III and OPV III for males as compared to 51.9 and 49.5%, respectively for girls. The drop out rates for DPT and OPV were also found to be higher (p greater than 0.05) in female children. However, no difference was observed in the reasons for non-immunization between the female and male children. PMID- 2210820 TI - Immunization coverage evaluation surveys in rural Narela zone and city zone areas of Delhi. AB - A major purpose of the immunization coverage evaluation surveys to document the vaccination status of children aged 1-2 years was to determine the true picture of the immunization status of the target population and to identify areas which need strengthening. Immunization coverage evaluation surveys were carried out for a 2.4 lakh rural and 2.2 lakh urban population of Delhi by the cluster sampling method. A total of 210 and 212 children, respectively aged 12 to 23 months, were included in the study in 30 randomly selected clusters in each zone. The percentage of children immunized with DPT3/OPV3/BCG was 70.0 and 73.1 in the rural and city zones, respectively while those immunized with DPT3/OPV3/BCG/Measles was only 30.0 and 37.3% in the two zones. Dropout rate for DPT and OPV, I to III was 16-18%. The drop out rate between DPT and OPV II and III was higher than that between DPT and OPV II and II. Percentage of non immunized children was significantly higher in rural (8.0%) as compared to urban areas (2.3%). Maximum immunizations were done by the Health Centres. Done on a periodic basis, a coverage evaluation survey will show whether or not vaccination coverage objectives have been met. PMID- 2210821 TI - Polycythemia in the newborn. AB - Polycythemia (venous PCV greater than 65%) in neonates is not an infrequent occurrence. Over the last 2 years out of approximately 1500 admissions to the Neonatal Unit, polycythemia was detected in 46 babies (3.06%). Seventeen (36%) of these babies were preterm and 29 (63%) were term. Approximately one third were small for dates while 2 babies (4%) were large for dates. Four of them had been born to mothers with gestational diabetes and 7 were twin deliveries. Severe perinatal asphyxia (5 minute Apgar score less than or equal to 5) was present in 12 cases (26%). Symptoms suggestive of polycythemia included lethargy in 15%, refusal to feed in 13%, respiratory distress in 10%, vomiting in 8% and abdominal distension in 6%. Associated hypoglycemia was seen in 5 cases (10.8%) while twelve babies (26%) had significant jaundice (bilirubin greater than or equal to 12 mg/dl). Twenty eight babies (60.8%) were given a partial plasma exchange transfusion through the umbilical route. There was 6.5% mortality in these 46 babies with polycythemia. Blood letting through a peripheral vein along with a plasma infusion may be a safer alternative to partial plasma exchange transfusion through umbilical route in babies with polycythemia. PMID- 2210822 TI - Neonatal outcome following cesarean birth: a prospective study. AB - Neonatal morbidity and mortality in 573 singleton cesarean born infants was recorded. In 70% of women, it was a primary cesarean section. The neonatal mortality was 3.6% in babies born to primigravida mothers and 9.8% in infants of multigravida. Mortality in male and female infants was 5.73 and 9.65%, respectively. Preterm infants registered more than 7 times higher mortality than term infants. Birth weight below 2000 g and above 3500 g were associated with higher asphyxia rate and neonatal death. Neonatal morbidity frequently encountered was birth asphyxia (19.19%), septicemia (13.43%), jaundice (15.70%) and respiratory problems (23.0%). PMID- 2210823 TI - Knowledge of nutritive values of foods and diet during diseases amongst nursing students. AB - Knowledge about nutritive value of foods and diet during diseases was assessed amongst forty nine nursing students at the beginning of their training course in Human Nutrition. Majority of the students had correct knowledge about dietary advice during antenatal and postnatal period. The knowledge of nutritive values of foods and diet during disease conditions was inadequate. PMID- 2210824 TI - Infant of the diabetic mother. PMID- 2210825 TI - Ceftriaxone. PMID- 2210826 TI - Reasons for delayed vaccination. PMID- 2210827 TI - Accidental poisoning in Benghazi, Libya. PMID- 2210828 TI - Etiological spectrum of viral hepatitis in children at Chandigarh. PMID- 2210829 TI - Autoimmune thrombocytopenia in newborn. PMID- 2210830 TI - Sacrococcygeal teratoma in children. PMID- 2210831 TI - Congenital midline subgaleal cyst. PMID- 2210832 TI - Rubinstein-Taybi syndrome. PMID- 2210833 TI - Hemostatic change in neonates with anoxia and sepsis. PMID- 2210834 TI - Acinetobacter calcoaceticus from blood culture of children. PMID- 2210835 TI - Rational drug treatment of acute upper respiratory infections. PMID- 2210836 TI - [Reuse of a bridge with carious abutments]. PMID- 2210837 TI - [Rotary insertion telescopic ceramometal pontics]. PMID- 2210838 TI - Bee venom immunotherapy. PMID- 2210839 TI - Am I an allright person? PMID- 2210840 TI - Principles of prevention: economics of prevention. PMID- 2210841 TI - Computerised nursing care plans: an integral part of hospital information systems. PMID- 2210842 TI - Where has all the money gone? Funding a study tour. PMID- 2210843 TI - Acute pain into the 90's. PMID- 2210845 TI - Predicting success in a pre-registration nursing program. AB - This article describes a pilot study which was carried out to determine whether, a relationship existed between either the matriculation scores or the biological science background of beginning student nurses, and their academic success in the three year pre-registration nursing program at Royal Adelaide Hospital. Information was obtained from the academic record cards of students who commenced the program in 1985. Statistical analysis using the Pearson r and Two-sample T test indicated a positive correlation between matriculation scores and academic results in each of the three years of the course. Surprisingly only 6 of the total number of students (N = 119) had not studied biology at matriculation level and hence analysis of this subject as a predictor of success was not possible. PMID- 2210844 TI - Hyperbaric oxygen therapy at Royal Adelaide Hospital--an historical perspective. PMID- 2210846 TI - Clinical nurse consultant: job share. PMID- 2210848 TI - The role of the transplant co-ordinator. PMID- 2210847 TI - An insight into cultural and social influences on health and illness--a student's perspective. PMID- 2210849 TI - The last round against bacterial infections? PMID- 2210851 TI - Vero cytotoxin-producing strains of Escherichia coli in children with haemolytic uraemic syndrome and diarrhoea in Czechoslovakia. AB - The presence of verotoxin-producing strains of Escherichia coli (VTEC) was examined in six children with haemolytic uraemic syndrome and one child with haemorrhagic colitis. Stools were screened for strains of serogroup O157 on sorbitol-MacConkey agar for VTEC of other serogroups by serotyping. Verotoxin (VT) was tested on Vero cell monolayers: the antigenic variant of VT was assessed by neutralization experiments. Strains producing verotoxin 1 or verotoxin 2 or both were detected in the stools of all seven children. Three strains belonged to serogroup O157 (two of them to serotype O157:H7, one was non-motile) and another five belonged to serogroups O26 (two strains), O1, O5 and O18. The faeces of five children available for testing contained free VT. Production of VT was also examined retrospectively in 32 E. coli strains of serotype O26:H11 isolated from children with diarrhoea; eight (25%) of them produced moderate to high levels of verotoxin 1 despite several years storage in vitro. In conclusion, VTEC including strains of serogroup O157 seem to be an important cause of haemolytic uraemic syndrome, haemorrhagic colitis and diarrhoea in children in Czechoslovakia. PMID- 2210850 TI - The incidence of fulminant hepatic failure in acute viral hepatitis in Taiwan: increased risk in patients with pre-existing HBsAg carrier state. AB - The incidence of fulminant hepatitis in Taiwan was studied in a series of consecutive 523 patients with acute viral hepatitis including 11 with acute hepatitis A, 67 with acute hepatitis B, 124 with acute hepatitis NANB and 321 acute hepatitis in HBsAg carriers (patients who were HBsAg positive but anti-HBc IgM negative). Thirty-eight (7.3%) were recognized as fulminant hepatitis. The incidence of fulminant hepatitis was relatively low in patients with acute hepatitis A, B or NANB (2.0% or 4 out of 202), but was much higher in HBsAg carriers with acute hepatitis (10.6% or 34 out of 321). The incidence of fulminant hepatitis correlated significantly with the pre-existing HBsAg carrier state after adjustment of the confounding effect of age. The incidence of fulminant hepatitis in HBsAg carriers with acute hepatitis showed no significant difference in relation to sex or to the presence of anti-delta in serum, but it increased proportionally with age. We concluded that the pre-existing HBsAg carrier state was a major risk factor for development of fulminant viral hepatitis. The etiology of superimposed acute hepatitis leading to fulminant hepatic failure might be varied according to the different geographic origins. PMID- 2210853 TI - Nosocomial infections in general surgery: surveillance report from a German university clinic. AB - At the general surgery clinics, University of Giessen, we developed our own system for surveillance of nosocomial infections according to the guidelines of the Centers of Disease Control. Atlanta, USA, and according to the results of the SENIC Project. We wanted to receive information about the overall infection rate, the procedure specific infection rate, site specific infection rate, distribution of nosocomial infections by pathogen and resistance pattern of antibiotics at the general surgery clinics. The overall infection rate of operations, classified as clean, clean--contaminated, and contaminated and dirty, was 13%. The surgical wound infection rate of 3% after clean operations was mainly caused by an elevated infection rate of 13% after clean operations of a prolonged duration and hyperthermic perfusion of the extremities in patients with melanoma. There is also a difference in nosocomial infection rates at the general surgery ward (11%) and at the intensive care unit (29%). At the intensive care unit candida and coagulase negative staphylococci are mainly isolated whereas Escherichia coli, Staphylococcus aureus and Enterococcus faecalis dominated the general surgery ward. Different operations show different distributions of isolates; operations on the pancreas are prone to have infections with coagulase negative staphylococci, candida and Pseudomonas aeruginosa. The antibiotic susceptibility tests for the most commonly used antibiotics revealed no resistance problems for E. coli, E. faecalis, and Staphylococcus aureus, common pathogens at the general surgery ward, but did for coagulase-negative staphylococci where we can consider only a few antibiotics like amikacin in obvious infections at the intensive care unit. PMID- 2210852 TI - Cerebrospinal fluid and serum neopterin levels in patients with Lyme neuroborreliosis. AB - Elevated (greater than 3.0 nmol/l) cerebrospinal fluid neopterin concentrations were observed in 20 of 21 patients with Lyme neuroborreliosis compared with three of 11 control patients with headache, back pain or psychoneurotic disorders. Neopterin concentrations were correlated to mononuclear cell counts and protein concentrations in the cerebrospinal fluid (CSF). Following antibiotic treatment, CSF neopterin levels decreased. Serum neopterin levels were not significantly raised in patients with neuroborreliosis when compared to control subjects. Neopterin levels as well as cell count and protein concentration in the CSF are valuable inflammation markers of disease activity in Lyme neuroborreliosis. PMID- 2210854 TI - Prolonged unexplained pyrexia: a review of 221 paediatric cases from Kuwait. AB - Over a three year period (January 1985 through December 1987), 221 children with prolonged pyrexia were admitted to the paediatric departments in two regional hospitals in Kuwait. Infections, connective tissue diseases and malignancies constituted 78%, 5% and 2%, respectively, and 15% of the cases remained undiagnosed. Brucella was the most common infectious agent encountered (38% of all cases), followed by typhoid fever (9%). The duration of fever was more helpful in the differential diagnosis than its height or pattern. The erythrocyte sedimentation rate and the white blood count were of limited value, and the C reactive protein was positive in bacterial infections, malignancies and connective tissue diseases. Since a child presenting with prolonged pyrexia in this country has over a 70% chance of having a bacterial infection, both diagnostic and therapeutic procedures should be performed as an emergency measure. Particular emphasis should be put on the exclusion of brucellosis. PMID- 2210855 TI - An outbreak of Acinetobacter calcoaceticus infection in a neonatal care unit. AB - Between January and December 1988, 383 neonates were admitted to our neonatal intensive care unit. 1,991 swabs and blood cultures were tested bacteriologically. Among them 90 specimens obtained from 41 patients were positive for Acinetobacter calcoaceticus. During this period we discovered and treated three cases with A. calcoaceticus sepsis. Three additional cases had blood cultures positive for this bacterium without demonstrating any clinical signs of infection. There is good evidence that contaminated warm air humidifiers were the source of infection. A review of microbiological data for several months preceding the outbreak showed a definite increase in the presence of A. calcoaceticus. The affected neonates required specific antibiotic therapy and intensive care. All of them survived. Conditions favoring the spread of these generally non-pathogenic bacteria and modes of preventive measures are discussed. The necessity of continuous bacteriological surveillance and careful disinfection of intensive care equipment is emphasized. PMID- 2210857 TI - Parenteral fluoroquinolones in children with life-threatening infections. AB - The new fluoroquinolones have not been tested in children despite their wide spectrum of in vitro activity and efficacy, because of an observed damage to cartilage in young animals. However, in some cases they may be life-saving. We present three pediatric patients with life threatening infections in whom the fluoroquinolones were used when other antibiotics failed: A seven-year-old boy with meningitis due to multiresistant Acinetobacter calcoaceticus, a three-year old boy with Job's syndrome with line sepsis due to Staphylococcus epidermidis and a four month-old boy with agammaglobulinemia with mixed infection due to Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter spp. All three children were cured of their infections. PMID- 2210856 TI - Ciprofloxacin in the treatment of nosocomial multiply resistant Acinetobacter calcoaceticus bacteremia. AB - Twelve cases of multiply resistant Acinetobacter calcoaceticus bacteremia occurred in three intensive care units in three different outbreaks. All patients were mechanically ventilated, on broad spectrum antibiotics and had central lines when bacteremia occurred. The sites of primary infection were: abdominal (n = 3); respiratory (n = 4); central lines (n = 4); CNS (n = 1). In eight cases the acinetobacter strains were susceptible to ciprofloxacin only. Four other strains were sensitive to amikacin as well. All 11 patients treated with ciprofloxacin alone (seven) or in combination with amikacin (four) fully recovered from the infection. The 12th patient died before antibiotic susceptibility was available. Ciprofloxacin seems to be an excellent therapeutic agent for A. calcoaceticus infections. PMID- 2210858 TI - Group C streptococcal pleurisy and pneumonia: a fulminant case and review of the literature. AB - A 30-year-old, previously healthy patient developed a pleurisy and pneumonia due to group C streptococcus, with multiple medical complications, including bilateral empyemas. Eight other reported cases of group C streptococcal pneumonia are reviewed. PMID- 2210859 TI - An antibiotic resistant experimental model of Pseudomonas osteomyelitis. AB - We report a model of chronic Pseudomonas aeruginosa osteomyelitis in the rat that was reproducible, simple and inexpensive. No promoting agent was required to cause infection. Infected animals yielded consistent pseudomonal colony counts (log): 4.98 +/- 0.32 (SD)/g cortical tibia (n = 16). The 95% confidence interval of the mean was 4.83-5.14. The inoculum required to infect 50% of challenged rats (ID50) was log 4.0; the ID 100 was log 6.4. Ceftazidime (50 mg/kg/8 h, subcutaneously), alone and in combination with tobramycin (40 mg/kg/12 h, subcutaneously), produced no significant change in quantitative bacterial count or gross bone pathology when used to treat established disease. PMID- 2210860 TI - Short term parenteral antibiotics used as a supplement to SDD regimens (Infection Suppl. 1, 1990, S 14-S 17) S. R. Alcock. PMID- 2210861 TI - Infectious mononucleosis and renal failure. PMID- 2210863 TI - Primary hemostasis in hemodilution--1) Hematocrit. AB - There are still controversies about the influence of acute preoperative hemodilution on coagulation. Therefore, we examined the platelet function by the In-vitro bleeding test (IVBT) using composed blood samples of different hematocrit but constant platelet concentration. We found an inverse correlation between hematocrit and bleeding time (p less than .05), volume (p less than .001) and flow (p less than .001). These data suggest a considerable impairment of primary hemostasis, due to low hematocrit. The cause may be an alteration of the hemorheology as well as the interaction between red cells and platelets themselves. PMID- 2210862 TI - [Maximal turnover rates of glycolysis enzymes and of the citrate cycle of separated granulocytes in the postoperative period]. AB - The human granulocyte is easy to obtain and shows a nearly complete enzymatic equipment. It therefore represents an interesting model for in-vitro studies of metabolic disorders under various clinical conditions. In the presented study, the activities of several enzymes of glycolysis and citric cycle are measured in granulocytes separated from surgical patients (n = 10). Blood samples of 20 to 40 ml were drawn 6.5 +/- 4.8 hours after termination of surgical procedure. All patients were artificially respirated and nourished intravenously according to the results of indirect calorimetry. Hexokinase (HK), pyruvate kinase (PK), lactate dehydrogenase (LDH), and isocitrate dehydrogenase (IDH) were measured photometrically in the cell homogenate. The values were compared to those determined in a group of healthy, not-anesthetized persons, nourished and studied identically (n = 12). In granulocytes separated from patients following major surgery we found increased activities of HK (29.8 vs. 24.1 mU/mg protein in controls), LDH (2,484 vs. 1,868 mU/mg protein, p less than 0.01) and IDH (41.5 vs. 35 mU/mg protein, p less than 0.05), and a reduced activity of PK (1,623 vs. 2,265 mU/mg protein, p less than 0.01). Assuming that the alterations in enzyme activities of isolated granulocytes reflect metabolic alterations of the whole organism to a certain extent, the results can be interpreted as a decreased induction of PK by insulin, an increase of lactate recycling via Cori cycle (LDH), and a stimulated substrate flux in citric cycle (IDH). The separated human granulocyte is recommended as a model of posttraumatic metabolic disorders. It should be taken into consideration for studies leading to further improvement of nutrition during posttraumatic glucose mal-utilization. PMID- 2210864 TI - Use of stroma for the detection of blood-group antibodies by ELISA. AB - A micro enzyme-linked immunosorbent assay (ELISA), using lyophilized stroma as carrier of red blood cell antigens, which stay stable longer than usual, using intact erythrocytes, was developed for determination of blood-group antibodies in the AB0, Kell and Lewis-systems. Stroma being fixed on microtiter plates was incubated with antisera and peroxidase-conjugated anti-human globulin. The transformation of the substrate added was determined photometrically. A binding of antibodies to the stroma could be demonstrated up to an antibody dilution of 1:1024 for the ABO-system, of 1:512 for the Kell-system and of 1:64 for the Lewis system. By standardization of this method the quantitative determination of antibodies becomes possible without being restricted by the limited stability of intact erythrocytes. PMID- 2210865 TI - Anti-lipopolysaccharide-immunoglobulin (IgG-anti-LPS) therapy in intensive care patients following surgery from infectious disease. AB - In 18 intensive care patients the effect of a IgG-Anti-Lipopolysaccharide (Anti LPS), was investigated in a randomized study following surgery after bacterial infections, mostly peritonitis. Fresh frozen plasma was administered during the first 5 postoperative days, containing either more than 65 micrograms/ml Anti-LPS in the therapy group or less than 12.5 micrograms/ml in the control group. The serum level of Anti-LPS was monitored. Clinical and chemical parameters were recorded to evaluate infectious complications and outcome of the patients. The mortality in the treatment group was not different from the control group with 30% (3 out of 10) and 25% (2 out of 8), respectively. No beneficial effect was observed either from the administration of Anti-LPS or from endogenously produced Anti-LPS on any clinical parameter in our patients. PMID- 2210867 TI - Phenotypic analysis of lymphocytes involved in major histocompatibility complex unrestricted cellular cytotoxicity in patients with alcoholic cirrhosis. AB - Lymphocyte subpopulations known to exert major histocompatibility complex (MHC) unrestricted cytotoxicity were enumerated in 33 patients with alcoholic cirrhosis and in 10 patients with alcohol-induced fatty changes of the liver. Absolute numbers and percentages of lymphocytes bearing the CD57 (median 12 vs. 20%; p = 0.007) and CD16 (median 12 vs. 19%; p = 0.0027) antigens were significantly reduced in cirrhotic patients as compared to healthy control individuals, whereas no significant change in CD56+ cells (median 13 vs. 13%; n.s.), comprising a subpopulation with a high natural killer activity in normal individuals, was observed. A subset of these cells, cytotoxic T cells coexpressing CD56 and CD3 antigens and capable of MHC-unrestricted cellular cytotoxicity, was significantly increased in patients with alcoholic cirrhosis as compared to healthy control individuals (median 2 vs. 1%; p = 0.024). Patients with alcohol-induced fatty changes of the liver did not show any deviation of lymphocyte subpopulation from normal. The finding that lymphocyte subsets capable to exert most of the MHC unrestricted cytotoxic capacity in peripheral blood (CD56+ non-T-cells and CD3+ CD56+ T cells) were unchanged or even increased in number suggests that the reduced natural killer cell activity known to occur in patients with alcoholic liver cirrhosis might be due to a functional defect of these cells. Furthermore, our results indicate that changes in frequency of MHC-unrestricted cytotoxic cells are not found in a similar manner in all subsets of these cells, but are dependent on the particular cell surface marker investigated. PMID- 2210868 TI - Immunogenicity of amodiaquine in the rat. AB - Amodiaquine is an antimalarial drug that has been associated with adverse reactions which may be immune mediated. Specific IgG anti-amodiaquine antibodies were detected after administration of the drug to rats (269 mumols/kg for 4 days), using an enzyme-linked immunosorbent assay employing amodiaquine conjugated to metallothionein as an antigen. A positive immune response was observed regardless of the route of administration, but the magnitude of the response in terms of antibody titre was in the order intraperitoneal administration greater than intramuscular administration greater than oral administration. Hapten inhibition experiments with structurally related drugs defined the specificity of the antibody which appears to recognize a conjugate of amodiaquine quinone imine and cysteine residues present in protein. Amodiaquine was converted to a protein-reactive species by activated human polymorphonuclear leucocytes in vitro, and this may provide a mechanism for immunogen formation in vivo. A humoral immune response was observed with doses of amodiaquine that did not produce either direct hepatotoxicity or leucopenia. Thus an animal model has been developed with which to investigate the toxicological consequences of amodiaquine immunogenicity. PMID- 2210866 TI - Voluntary blood donor recruitment: a strategy to reduce transmission of HIV-1, hepatitis-B and syphilis in Kinshasa, Zaire. AB - We evaluated the use of voluntary blood donor recruitment in Kinshasa, Zaire, as a means of reducing transmission of HIV-1 and other infectious agents by blood transfusion. Between January 1, 1989, and April 7, 1989, 2,237 blood donors were enrolled in the study at the transfusion centre of the Mama Yemo Hospital. Each donor was tested for antibodies to HIV-1 confirmed by IFA and Western blot, Treponema pallidum, antibodies to hepatitis B virus (HBV) core antigen and screened for the presence of the HBV surface antigen. Test results were related to the data of the blood donors: age, sex, haematocrit, voluntary blood donor, family member donor, paid donor. The serological results of all donors for Anti HIV-1. Anti-HBc, HBsAg and TPHA were 4.8%, 70.9%, 13.1% and 13.3% respectively. Lower seroprevalence rates were found among voluntary blood donors. However, only TPHA seroprevalence was significantly lower in voluntary blood donors (8.4%, 23/275) compared with paid donors (15.2%, 87/571) (p less than 0.01). A greater proportion of voluntary donors provides a store of blood which allows more extensive screening of blood for HIV-1 and other infectious diseases. Voluntary blood donor recruitment is critical for the provision of safe blood supplies in Kinshasa. PMID- 2210869 TI - Identification of a 'disease-associated' antigen in pigeon breeder's disease by western blotting. AB - Sera from 9 symptomatic and 7 asymptomatic pigeon breeders were analyzed for their reactivity to pigeon serum by western blotting. All 9 symptomatic sera (9/9; 100%) and only 4 of 7 (57%) asymptomatic sera revealed specific antibodies. The immunoreactivity patterns of the sera varied: the majority of the sera reacted to antigens having molecular weights of 220 kD or more (9/16 sera), 98 kD (8/16 sera), and 86 kKD (8/16 sera). However, only sera from symptomatic breeders recognized an antigen of approximate molecular weight of 29-32 kD (9/9; 100% of symptomatics). We conclude that this antigen is 'disease associated' and may be useful in the diagnosis of pigeon breeder's disease. PMID- 2210870 TI - Expression and distribution of Ia antigen in the murine small intestine. Influence of environment and cholera toxin. AB - Density and distribution of Ia antigen in the small intestine of C57bl/6 mice showed substantial differences, depending on the environment in which they were reared and maintained. Isolator-reared mice expressed low levels of epithelial Ia antigen in comparison to mice reared in a conventional environment. Oral administration of 10 micrograms of cholera toxin had no effect on the level of epithelial Ia expression. We conclude, therefore, that the mechanism whereby cholera toxin is able to potentiate mucosal responses to fed antigens is not related to changes in the level of epithelial Ia expression. PMID- 2210871 TI - Human recombinant lymphokines and cytokines induce pulmonary eosinophilia in the guinea pig which is inhibited by ketotifen and AH 21-132. AB - Subcutaneous or intraperitoneal injection of recombinant human granulocyte macrophage colony-stimulating factor, interleukin 3, or mouse tumour necrosis factor alpha, but not recombinant human interferon gamma, platelet-derived growth factor, or transforming growth factor beta caused selective eosinophilia of the pulmonary airways in the guinea pig. Unlike responses to platelet-activating factor, there was no attendant detectable airway hyperreactivity, but in common with responses to platelet-activating factor, eosinophilia of the airways was prevented by pretreatment with ketotifen or AH21-132. Cytokines or lymphokines may contribute to pulmonary eosinophilia in diseases such as asthma. PMID- 2210873 TI - Inhibition of IgE-mediated N-acetylglucosaminidase and serotonin release from rat basophilic leukemia cells (RBL-2H3) by tenidap: a novel anti-inflammatory agent. AB - Tenidap [(Z)-5-chloro-2,3-dihydro-3-(hydroxy-2-thienylmethylene)-2-oxo-1H- indole 1-carboxamide] is a novel anti-inflammatory compound of the oxindole class that currently is undergoing clinical evaluation in man. Here we demonstrate that tenidap inhibits (IC50 = approximately 10 microM) IgE-mediated secretion of granule constituents from the rat mast cell tumor line RBL-2H3. The inhibitory effect is rapid in onset, readily reversible, and appears to be unique when compared to a representative selection of other acidic (carboxylic acids, pyrazoles and oxicams) nonsteroidal anti-inflammatory compounds. PMID- 2210872 TI - Isolation and characterization of a cDNA clone encoding an IgE-binding protein from Kentucky bluegrass (Poa pratensis) pollen. AB - We reported previously on the isolation and characterization of several allergens from Kentucky bluegrass (KBG) (Poa pratensis L.) pollen with the aid of the corresponding murine monoclonal antibodies (Mabs). In the present study, (1) an analysis of various tissues of this grass revealed that the allergenic components recognized by these Mabs were confined to the pollen; (2) intact translatable mRNA was isolated from the KBG pollen, and (3) a cDNA library was constructed with this mRNA in the lambda gt11 expression vector. Screening of this library with a pool of six sera from KBG-allergic patients, in combination with enzyme labeled antibodies to human IgE, led to the isolation of a cDNA clone, referred to as KBG7.2. The nick-translated cDNA probe of KBG7.2 hybridized to a 1.5-kbp RNA transcript from KBG pollen. Moreover, transcripts corresponding to KBG7.2 were found in pollens of eight other grasses, indicating that the proteins similar to the one encoded by this cDNA may be present in these grasses. The nucleotide sequence of KBG7.2 was determined; interestingly, the corresponding derived amino acid sequence did not match any other sequence recorded in the protein data banks. The peptide encoded by KBG7.2 was expressed as a fusion protein utilizing the plasmid vector pWR590.1. Whereas none of the above allergen specific Mabs bound to the fusion protein, all the 15 individual sera from grass pollen allergic patients recognized the fusion protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210874 TI - Induction of interleukin-1-beta release from human monocytes by cotton bract tannin. AB - The human T lymphocyte proliferative response to cotton bract tannin was shown to be dependent upon the presence of monocytes. Since monocytes support the T cell mitogenic response by interleukin-1 (IL-1) production, it was anticipated that tannin has IL-1-inducing ability. To examine this possibility, human monocytes were cultured alone or with peripheral blood T lymphocytes, and stimulated with tannin. Control cultures included unstimulated cells, and cells challenged with other IL-1 inducers: concanavalin A (Con A) and lipopolysaccharide from Escherichia coli or Enterobacter agglomerans. IL-1 beta was measured in culture supernatants 24 h after initiation of the culture by the use of an ELISA or an RIA. The results showed that tannin stimulated monocytes to secrete IL-1 beta in a manner similar to Con A, i.e. substantially more cytokine was measured in the supernatants of monocyte-T-lymphocyte co-cultures than in the cultures of monocyte alone. Endotoxin from E. coli was less effective than the endotoxin from E. agglomerans in IL-1 induction. Contaminating endotoxin present in the tannin preparation accounted for the majority of IL-1 beta released from monocytes alone stimulated with tannin, but only 20% of the IL-1 beta released from tannin stimulated monocyte-T-lymphocyte co-cultures. These results show that tannin itself has IL-1-inducing ability. The dose-response studies show that the extent of IL-1 beta release is dependent on tannin dose and that increased levels of monocyte-produced IL-1 beta precede the increase in T lymphocyte proliferation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210875 TI - Degranulation of mast cells in the trachea and bronchi of the rat following stimulation of the vagus nerve. AB - In the trachea and bronchi of the atropinized rat, the proportion of degranulating mast cells (defined as having one or more granules outside the body of the cell in a 10-microns thick section) was increased from 35-40% to 48-55% following electrical stimulation of one or both vagus nerves for 3 min. The increase occurred bilaterally, though it was greater on the stimulated side. The degranulation of mast cells was prevented by transection of the nerve rostral to the nodose ganglion 8-10 days before stimulation. Pre-treatment of rats with capsaicin also prevented the degranulation of mast cells that otherwise would have followed stimulation of the vagus nerve. These observations indicate that tracheo-bronchial mast cells discharge their granules in response to the activity of capsaicin-sensitive axons of neurons whose cell bodies are rostral to the nodose ganglion. These are probably substance P-containing polymodal nociceptive neurons of the jugular ganglion. If similar neurons exist in man, axon reflexes in their intrabronchial branches would be expected to stimulate the release of mast cell-derived agents that cause bronchoconstriction in asthma. PMID- 2210876 TI - Monoclonal antibodies to proteins from cocksfoot grass (Dactylis glomerata) pollen: isolation and N-terminal sequence of a major allergen. AB - Monoclonal antibodies (Mabs) raised to an aqueous extract of cocksfoot grass (Dactylis glomerata) pollen have been characterised. Mab 1B9 was demonstrated by SDS-PAGE and Western blotting to recognise a major allergen of an approximate molecular weight of 28 kD in this extract, termed DG3, and a component with a molecular weight of between 35 and 40 kD in an extract of Secale cereale (cultivated rye) pollen. The 28 kD component of cocksfoot grass pollen isolated by affinity chromatography using Mab 1B9 was recognised by IgE antibodies in 80% (8 of 10) atopic sera, but only weakly by 25% (1 of 4) non-atopic sera tested. N terminal sequencing of DG3 purified by affinity chromatography, 2 D electrophoresis and electroblotting to polyvinylidenedifluoride revealed significant homology with a group-V allergen (Phl p V) from timothy grass (Phleum pratense). PMID- 2210877 TI - IgG-class insulin autoantibodies in autoimmune thyroid disease. AB - We studied the incidence of insulin autoantibodies (IAA) in 97 patients with autoimmune thyroid disease with an enzyme-linked immunosorbent assay. The sera were also tested for islet cell antibodies (ICA) and thyrotropin receptor antibodies (TRAb). IAA as assessed by a standard deviation score were present in 7 patients (7.2%). None of the patients were seropositive for ICA. Data from this random sampling and a retrospective study of 12 patients on antithyroid drug treatment indicated that the presence of IAA was not associated with TRAb. PMID- 2210878 TI - Induction of HLA class I surface expression recruits low-affinity cytolytic T lymphocytes. AB - Recent studies indicate that the relative expression of HLA class I molecules can play an important role in regulating the cellular immune response. In this report, we used cloned human cytolytic T lymphocytes (CTL) and transfected HLA class I molecules to investigate the effect of HLA class I induction on CTL reactivity. CTL clones with identical antigen specificities but different antigen affinities were compared for their ability to lyse target cells with varying levels of HLA class I expression. The cytolytic reactivity of the high-affinity clone was independent of the level of HLA class I expression. In contrast, cytolytic reactivity of the low-affinity CTL clone was directly related to the level of HLA expression. These data suggest that the induction of HLA class I surface expression has a disproportionate effect on the reactivity of low affinity CTL and may provide a mechanism for the recruitment of these cells in vivo. PMID- 2210879 TI - Specific chromosomal mutagenesis observed in stimulated lymphocytes from patients with S-ANLL. AB - An analysis of R-banded PHA-stimulated lymphocytes from 13 patients with secondary acute non-lymphocytic leukemia (S-ANLL) following breast cancer or lymphoma, and treatment by alkylating agents and/or radiotherapy, is reported. We found that chromosomes 5, 7, 11 and 17 are over-involved in structural rearrangements. These anomalies are similar to those observed in the same categories of patients without S-ANLL, and after in vitro treatment of normal lymphocytes by the alkylating agent melphalan. These anomalies are thus likely to be induced by treatment, independently of S-ANLL. However, the same chromosomes (5, 7, 11 and 17) are recurrently deficient in leukemic S-ANLL clones. In spite of these similarities, it remains unlikely that the deficiencies observed in leukemic clones were directly induced at the time of treatment. Probably, treatment of primary cancers induces nonrandom mutations of recessive genes located on these chromosomes as also indicated by chromosomal lesions. Various rearrangements including deletions of the homologous normal counterparts may then occur, unmasking mutated recessive genes. The latter stage would be concomitant with the leukemogenic process. PMID- 2210880 TI - Influence of cigarette smoking on the levels of DNA adducts in human bronchial epithelium and white blood cells. AB - The presence of carcinogen-DNA adducts in human tissues is evidence of exposure to carcinogens and may be an indicator of cancer risk. DNA was isolated from non tumorous bronchial tissue of 37 cigarette smokers, 8 former smokers and 8 non smokers and analyzed for the presence of aromatic and/or hydrophobic DNA adducts in the 32P-post-labelling assay. Adducts were detected as bands of radioactive material when 5'-32P-labelled deoxyribonucleoside 3',5'-bisphosphates were chromatographed on polyethyleneimine-cellulose tlc plates, and the patterns indicated the formation of adducts by a large number of compounds. Adduct levels detected in DNA from non-smokers, former smokers and current smokers were 3.45 +/ 1.62, 3.93 +/- 1.92 and 5.53 +/- 2.13 adducts/10(8) nucleotides, respectively. The differences in adduct levels between smokers and former and non-smokers were statistically significant (p less than 0.01); and among the smokers, significant correlations were found between adduct levels and both daily cigarette consumption and total cigarette consumption (daily consumption X number of years smoked). DNA was also isolated from the peripheral-blood leukocytes of 31 heavy smokers (greater than 20 cigarettes/day) and 20 non-smokers and analyzed by 32P post-labelling. Adduct levels in the smokers' samples were not significantly different from levels in the non-smokers' samples (2.53 +/- 1.31 and 2.12 +/- 1.44 adducts/10(8) nucleotides, respectively). Thus, evidence for carcinogen exposure was found in human bronchial epithelium, a target tissue for tobacco induced tumour formation, but not in peripheral-blood cells, indicating possible limitations in the use of the latter as a surrogate, non-target tissue source of DNA for monitoring human exposure to inhaled carcinogens. PMID- 2210881 TI - Geographic association of Helicobacter pylori antibody prevalence and gastric cancer mortality in rural China. AB - To examine the geographic association between Helicobacter pylori infection and gastric cancer, we have assessed the prevalence of IgG antibodies to H. pylori in plasma samples taken in 1983 from 1882 men, aged 35-64 years, in 46 rural counties of the People's Republic of China. The gastric cancer mortality rates in these countries in 1973-75 varied from 3 per 1,000 (cumulative rate, 0-64 years) to 69 per 1,000, while the proportions of the population positive for H. pylori antibodies (based on an average of about 41 men per county) varied from 28% to 96%. After correction for the limited number of blood samples per county, the estimated correlation between H. pylori antibody prevalence and gastric cancer mortality was 40% (p = 0.02). No other type of cancer showed a significant association with H. pylori. PMID- 2210882 TI - Western blot analysis of serological responses following immunization with vaccinia viral lysates of melanoma cells. AB - Western blot analysis was used to characterize the antibody response of melanoma patients during immunization with vaccinia-virus-induced melanoma cell lysates (VMCL). Strong antibody responses were detectable within 4 weeks from commencement of immunization against different fractions (from 3 to 10) in blots of VMCL. The approximate MW of the main fractions identified were 100, 91, 85, 77, 64-66, 49, 46, 43 and 34-36 kDa. Comparison of the reactivity of the sera with extracts of vaccinia virus suggested that the reactivity against VMCL was not against viral antigens in the lysates. Studies on autologous extracts from 7 patients immunized with VMCL indicated that the majority of the fractions identified in extracts of VMCL were also identified in autologous extracts of melanoma cells. This indicated vaccine-induced responses against the patients' tumor cells and not merely against alloantigens in the vaccine. Sera from the immunized patients appeared to identify a number of fractions of similar MW in extracts of colon and glioma cells, suggesting that the responses were not specific for melanoma. Possible exceptions were reactivity against melanoma fractions of 85, 64-66 and 36 kDa. Our studies provide evidence for the effectiveness of VMCL in inducing antibody responses against autologous melanoma cells and form a basis for subsequent biochemical and genetic analysis of the antigens identified by antibody responses in immunized patients. PMID- 2210883 TI - Histologic variation among experimental tumors of common origin: relationships to viral p21 expression and to tumor-derived extracellular matrix. AB - Transformed lines, obtained by infection of adult rat adrenocortical fibroblast like cells with Kirsten murine sarcoma virus, produce s.c. tumors which range histologically from fibrosarcomas to carcinomas to undifferentiated neoplasms. This study was undertaken to determine whether the histology was a stable characteristic of individual lines and whether it was related to oncogene expression and to differentiation in culture. Three lines were infected at passage 1 and tumor histology, differentiation markers and expression of the transforming protein v-p21 were evaluated periodically over a 1-year period. The original stromal characteristics of the target cells (metachromatic extracellular matrix (ECM), a high rate of collagen production and collagen incorporation into ECM, and a fibroblastic morphology) diminished with transformation. In contrast, parenchymal differentiation markers (lipid, steroidogenic enzymes) were enhanced and constitutively expressed in all lines. The two lines in which ECM production was most reduced formed carcinomas in vivo, while the third line showed a smaller shift in these characteristics and formed sarcomas. Thus, histopathology seemed to be influenced by tumor-derived ECM but unrelated to the expression of steroidogenic properties. The tumors became less differentiated with time, but retained distinct line-specific phenotypes. Throughout the study, v-p21 remained overexpressed in all lines to a similar degree, but the subcellular localization of v-p21 differed between fibroblastic and epithelial cells, suggesting a possible correlation with differentiation. PMID- 2210885 TI - Effect of plasma gangliosides on the growth of Ehrlich ascites tumor. AB - Total plasma gangliosides of Ehrlich ascites tumor-bearing mice enhanced tumor growth when adoptively transferred with the same tumor cells in mice. However, individual gangliosides acted differently. Out of 6 gangliosides separated from plasma, 2 components enhanced tumor growth, whereas the remaining 4 inhibited tumor growth. Neither of the 2 enhancing components in various combinations with the 4 inhibitory components could restore the enhancing effect. The enhancing effect was restored only when both the enhancing components were mixed with the remaining 4 ganglioside components, i.e., with full/complete reconstitution. PMID- 2210884 TI - Quantity and saturation degree of dietary fats as modulators of oxidative stress and chemically-induced liver tumours in rats. AB - Male rats were fed, from weaning onwards, either 2, 12.5 or 25% sunflower seed oil (polyunsaturated fatty acids, PSA) or lard (saturated fatty acids, SFA) and from the age of 15 weeks subgroups were given N-nitrosodimethylamine (NDMA) for 30 weeks. Blood levels of lipids were assayed and during the study exhaled ethane was measured as an index of in vivo lipid peroxidation (LPO). At the age of 50 weeks, rats were killed and livers were analysed for tumours. PSA diets decreased plasma cholesterol and triglyceride concentrations vs. respective SFA diet; NDMA administration did not affect plasma cholesterol but enhanced triglyceride concentration. NDMA markedly enhanced LPO. An increase in dietary fat content from 2 to 25% enhanced ethane exhalation, more in rats fed PSA than the SFA diet. In the 25% PSA group, indomethacin in the diet strongly inhibited LPO. Prevalence of liver haemangiosarcomas increased from 42% to 80% (p less than 0.05) in NDMA treated animals when PSA increased from 2 to 25%; in the group having a 25% PSA diet containing indomethacin, the NDMA-induced tumour incidence was reduced to 64%. In NDMA-treated rats fed SFA diets the prevalence of haemangiosarcoma increased from 43% (2% fat) to 67% (25% fat). The data show that NDMA modifies plasma lipids and increases LPO. The quantity and saturation degree of fats altered the frequency of chemically-induced tumours and modified LPO. As an index of free radical reactions, LPO may have an important role in carcinogenesis. Dietary fat thus appears to promote carcinogenesis through mechanisms that involve LPO. PMID- 2210886 TI - Hyperplasia of mouse duodenal crypts and its control by NK cells during the initial phase of DMH carcinogenesis. AB - The possible regulatory role of NK cells on early events in chemical carcinogenesis remains undefined. The present study examined whether NK cells control 1,2-dimethylhydrazine (DMH)-induced hyperplasia of the duodenal crypt in CD1 mice. Mice receiving chronic DMH treatment showed a dose-dependent hyperplasia confined to the proliferative zone, with a parallel increase in mitotic and 3H-TdR-labelled cells and significant suppression of splenic NK activity. Complete ablation of splenic NK activity with anti-asialo GM-I antibody (alpha AGM-I) treatment slightly enhanced hyperplasia. Halving of the DMH dose for 2 weeks led to regression of hyperplasia, which was totally prevented by alpha AGM-I treatment. The alpha AGM-I treatment alone did not influence crypt size in normal mice. Finally, a stimulation of NK activity with Poly I:C treatment in DMH-treated mice caused regression of the DMH-induced hyperplasia. Our results suggest that hyperplastic cells with possible genetic alterations induced by the carcinogen express target structures for NK cells, but that simultaneous carcinogen-induced suppression of NK activity hampers their containment, allowing progression of hyperplasia to neoplasia, possibly owing to additional genetic changes. PMID- 2210887 TI - Aluminum phthalocyanines with asymmetrical lower sulfonation and with symmetrical higher sulfonation: a comparison of localizing and photosensitizing mechanism in human tumor LOX xenografts. AB - A comparison of time-dependent localization patterns between lower, asymmetrical (AIPCS2a) and higher, symmetrical (AIPCS4) sulfonates of aluminum phthalocyanines in human malignant melanoma LOX transplanted to athymic nude mice from 1 to 120 hr after i.v. administration was made by means of laser scanning fluorescence microscopy. The lipophilic AIPCS2a was distributed mainly in tumor cells, while the hydrophilic AIPCS4 localized only in the vascular stroma of the tumor tissue. Concomitantly, comparative observations on the killing mechanism of photodynamic effects after treatment with a much lower i.v. dose of AIPCS2a and AIPCS4 plus laser light on the human tumor LOX were also made by morphological studies. Light and electron microscopy showed that there was a direct, extensive, photo-damaging action on all organelles and nuclear structure in the tumor cells after PDT with AIPCS2a; whereas the photo-induced injury to the tumor tissue after treatment with AIPCS4 and light was largely the consequence of initial functional vasogenic response and ultimate damage to vascular structure. These findings correlate well with the different localization patterns of the 2 dyes observed in human tumor tissues. PMID- 2210888 TI - Epidermal cell-shape regulation and subpopulation kinetics during butyrate induced terminal maturation of normal and SV40-transformed human keratinocytes: epithelial models of differentiation therapy. AB - Recent data indicate that malignant human epidermal cells may be appropriate targets for sodium butyrate (NaB)-mediated differentiation therapy. The response of pre- and post-crisis populations of SV40-transformed human keratinocytes (SVKs) to this differentiation-inducing agent was assessed, therefore, within the framework of NaB-directed normal human keratinocyte (NHK) maturation. NaB augmented cornified envelope (CE) production in NHK and pre-crisis SVK cultures; the time-course and efficiency of induced maturation were similar in the 2 cell systems. In NHKs, the percentage of amplifying ("B" substate) cells decreased with time in NaB correlating with increases in both "C" stage keratinocytes and CEs. The latter formed over one or 2 layers of nucleated basal-like cells. Inductions were accompanied by immediate cell cycle blocks (in both the G1 and G2/M phases), reorganization within the actin cytoskeleton, and transient early increases in cellular actin content. Increased NHK and pre-crisis SVK cytoskeletal-associated actin reached a maximum approximately 48 hr after NaB addition and preceded development of CEs. The CE precursors, thus, probably reside in the "B" substate. Post-crisis SVKs, in contrast, were refractive to NaB induced terminal maturation or cell-cycle perturbation, failed to initiate actin filament rearrangements, and retained a basal cell-like phenotype. Stable transformation of human SVKs in post-crisis phase, therefore, appears to be associated with loss of maturation "competence" within the "B" keratinocyte subpopulation. PMID- 2210889 TI - Diabetes and breast cancer risk. PMID- 2210891 TI - Trends in multiple myeloma. PMID- 2210890 TI - Cellular senescence human chromosome 1 and carcinogenesis. PMID- 2210892 TI - Atherogenesis and the coronary arteries of childhood. AB - The coronary arterial intima undergoes a sequence of changes following injury, before the appearance of lipids. Studies of the evolution of coronary arterial pathology in the transplanted human heart defines a pattern which is the stereotype of the artery's response to insult. The first stage is that of intimal hyperplasia and disruption of the internal elastic lamina; the second the migration into the thickened intima of medial smooth muscle cells; the third the incursion of lipids. The end result is atheroma, indistinguishable morphologically from that which is found in the usual setting. The same sequence of arterial events can be sought, and found, in the general population (at least in coronary-prone societies), the first being identifiable commonly in infancy and childhood. These changes, reported in the literature over many years, have been generally assumed to be benign accompaniments of growth and development. They are likely to be the precursors of atherosclerosis and the seat of later lipid deposition, without which that deposition would not occur. The cause(s) of coronary arterial disease are therefore concerned more with these pre-lipid stages than with the lipids themselves, which are complicating rather than causative factors. PMID- 2210893 TI - Correlation between gallium-67 imaging and endomyocardial biopsy in children with severe dilated cardiomyopathy. AB - Fourty-four patients (aged 10 months to 15 years) were assessed in a double-blind study to observe the correlation between myocardial uptake of 67-gallium and endomyocardial biopsy in the detection of moderate to severe myocardial inflammation. The sensitivity and specificity of gallium-67 imaging were 87 and 81%, respectively. Based on these findings, immunosuppressive therapy can be assigned to children with dilated cardiomyopathy and positive myocardial uptake, since moderate and severe myocardial inflammation may be detected by this non invasive method. PMID- 2210895 TI - Pharmacologic modifications of reperfusion arrhythmias in the dog in vivo: possible relation to limitation of the extent of infarction. AB - To study the effects of pharmacologic interventions on reperfusion-induced arrhythmias, open chest anesthetized dogs were subjected to occlusion of a coronary artery for 3 hours followed by reperfusion for 3 hours. Electrocardiograms were recorded with a two-channel monitor with the subsequent recordings submitted to computer-assisted analysis. The extent of myocardial infarction was measured by staining with triphenyl tetrazolium chloride. Mexiletine (12 mg/kg) and verapamil (0.9 mg/kg) were given, starting at 120 min of coronary occlusion and continued until the end of experiments. Dibunol (60 mg/kg) was administered at 120 min of ischemia. Dibunol and dibunol together with verapamil reduced the extent of infarction (to 62 +/- 6% and 53 +/- 4% of the zone at risk, respectively; compared to 77 +/- 3% of the zone at risk in the control group, P less than 0.05) while verapamil alone and mexiletine did not. There were 5 fatal episodes of ventricular fibrillations in 23 dogs, together with other malignant arrhythmias when occlusion was released in the control group. Mexiletine and verapamil prevented these episodes of ventricular fibrillation during reperfusion while dibunol, and dibunol together with verapamil, did not. Apart from fibrillations, mexiletine eliminated ventricular tachycardias, in contrast to the other drugs, which did not. Mexiletine and verapamil alone prevented ventricular premature beats while dibunol, and dibunol with verapamil, exacerbated their generation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210894 TI - The potential value of transoesophageal evaluation of individual pulmonary venous flow after an atrial baffle procedure. AB - Following a Mustard's procedure, transoesophageal echocardiography allowed the visualization of all 4 pulmonary veins in 7/12 patients (mean age 14.8 years) and of three veins in a further 2 patients. Both upper pulmonary veins could be visualized consistently. No patient had an isolated pulmonary venous stenosis. In 9 patients in sinus rhythm, computer analysis of Doppler tracings from the left upper pulmonary vein showed significantly lower systolic peak velocities (mean 0.39 +/- 0.10 m/s) and time velocity integrals (mean 6.9 +/- 1.66 cm) than in normal subjects (mean 0.6 +/- 0.09 m/s and 14.4 +/- 2.97 cm respectively; P less than 0.001). We postulate that this is due to compromised atrial relaxation and compliance. In contrast, patients in junctional rhythm (mean 10.7 vs. 7.7 cm in normal subjects). Flow reversal during early ventricular systole (due to tricuspid regurgitation or atrial contraction after retrograde conduction during junctional rhythm) was detected in 6/12 patients. These results confirm that the transoesophageal approach should allow the identification of isolated pulmonary venous obstruction after a Mustard procedure. In addition. detailed analysis of tracings of flow in the pulmonary veins can document the presence of compromised atrial relaxation and help to evaluate the severity of tricuspid regurgitation. It may provide a new index with which to assess impaired systemic ventricular function. PMID- 2210896 TI - Right versus left ventricular stimulation: influence on induction of ventricular tachyarrhythmias in dogs. AB - The contribution of left (versus right) ventricular stimulation to the induction of ventricular tachyarrhythmias was studied in 37 dogs with chronic experimental myocardial infarction, and 17 dogs with normal hearts. Programmed stimulation of the endocardium at both ventricular apices employed an aggressive protocol of up to 7 extrastimuli. The right ventricle was the most successful site for induction of ventricular tachycardia after myocardial infarction (74% of dogs with ventricular tachycardia). Ten of 11 animals with slow ventricular tachycardia (greater than or equal to 140 msec) were inducible from the right ventricle. In contrast, left ventricular stimulation was required to induce rapid ventricular tachycardia (cycle length less than 140 msec) in 5 of 10 dogs (P less than 0.05). No animal required more than five extrastimuli from any site for induction of ventricular tachycardia. In the normal heart, ventricular fibrillation was induced most often from the right ventricle (77% of dogs) when compared with the left ventricle (47%, P less than 0.05). Ventricular tachycardia was never induced in normal animals. These results show that the right ventricular apex is the most successful site for induction of "slow" ventricular tachycardia in this canine model when using five extrastimuli. Rapid ventricular tachycardia is frequently induced from the infarcted left ventricle, but this arrhythmia may not be clinically significant. The normal right ventricle is significantly more susceptible to ventricular fibrillation than is the left ventricle, but this does not interfere with induction of ventricular tachycardia in the infarcted heart. PMID- 2210897 TI - Prevalence and extent of right ventricular dysfunction after myocardial infarction--relation to location and extent of infarction and left ventricular function. AB - In view of today's efforts to preserve myocardial function in acute myocardial infarction, the prevalence and extent of persistent right ventricular dysfunction was analysed in a prospective study of 127 patients admitted with a first myocardial infarction without thrombolysis. Right ventricular ejection fraction measured at hospital discharge by radionuclide angiocardiography was related to the location of infarction as judged electrocardiographically, its size as estimated enzymatically, and by the simultaneously measured left ventricular ejection fraction. Two opposite patterns of right and left ventricular function were observed in relation to the location of infarction: the right ventricular ejection fraction was significantly depressed in inferior, but not in anterior, infarction and the reverse was true for left ventricular ejection fraction (P less than 0.001 between infarct locations for both right ventricular ejection fraction and left ventricular ejection fraction). There were significant correlations between peak levels of creatine kinase and left ventricular ejection fraction for anterior (r = 0.76, P less than 0.001) and inferior (r = 0.57, P less than 0.001) infarction, while peak levels of creatine kinase and right ventricular ejection fraction correlated only in inferior infarction (r = 0.45, P less than 0.01). There was no overall correlation for left ventricular ejection fraction and right ventricular ejection fraction (r = 0.28, P NS), despite the fact that right ventricular ejection fraction was lower in patients with severely reduced left ventricular ejection fraction than in those with normal left ventricular function (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210898 TI - Coronary angioplasty in patients with prior coronary artery bypass grafting. AB - We studied the clinical and angiographic outcome of patients with prior coronary arterial bypass grafting who underwent percutaneous transluminal coronary angioplasty at the Royal Infirmary of Edinburgh. Over a 4 year period, 47 patients with prior bypass surgery underwent angioplasty of 23 stenotic graft sites and 37 stenotic sites of native vessels. The procedure was performed a mean of 31.3 months after surgery for recurrence of symptoms refractory to maximal medical treatment. Satisfactory angiographic results were achieved in 42 patients (58 stenotic grafts or native vessels). At a median follow up period of 18 months, 20 patients were symptomatically improved, but 22 patients experienced recurrence of symptoms a mean of 4.7 months after angioplasty, despite a good initial angiographic result. Overall, 4 patients had a repeat bypass grafting and 9 patients had a repeat angioplasty. Angioplasty can be used as an alternative to a repeat operation in patients with prior bypass grafting who experience recurrence of symptoms. Initial success rates are high and complication rates low. Restenosis or development of new lesions in the native circulation, and/or in the grafts, remain significant problems. Patients with a long asymptomatic interval (greater than 6 months) between the bypass operation and recurrence of symptoms are more likely to have better long-term results after successful angioplasty, perhaps because of slower progression of atherosclerotic heart disease. PMID- 2210899 TI - Enalapril as initial and sole treatment in severe chronic heart failure with sodium retention. AB - Five patients, who had never received any drug treatment but who had severe chronic congestive heart failure with salt and water retention, were studied before and after a single dose of enalapril (10 mg orally). Three patients continued on enalapril as monotherapy (10 mg b.d. orally) for one month. Central haemodynamics, body fluid volumes, renal function and plasma hormones were measured at rest. The initial mean right atrial pressure was 13 +/- 4 mm Hg, pulmonary wedge pressure 29 +/- 4 mm Hg and cardiac index 1.8 +/- 0.21/min/m2. Enalapril, given acutely, caused only small changes. Two patients were withdrawn after the single dose of enalapril and treated with diuretics for clinical reasons. The remaining three patients each lost more than 4 kg in weight after one month of treatment with enalapril alone. Total body exchangeable sodium and total body water were reduced but central haemodynamics were unchanged. Although enalapril was of some benefit when given alone to patients with severe congestive heart failure, all five patients were finally treated with diuretics for clinical reasons. Enalapril is not recommended as the initial and only therapy for patients with severe congestive heart failure. PMID- 2210900 TI - Clinical use of transoesophageal atrial stimulation in terminating ventricular tachycardia. AB - This study was performed to evaluate whether transoesophageal atrial pacing could also stop ventricular tachycardias with low rates and no haemodynamic impairment. Prior to resorting to ventricular endocardial pacing, seven male patients, aged between 15 and 73 years, were treated by transoesophageal atrial pacing for 10 spontaneous episodes of sustained ventricular tachycardia at rates between 105 and 160 beats per minute, without haemodynamic impairment. When atrial pacing did not allow ventricular capture, atropine sulphate was administered. Transoesophageal atrial pacing led to ventricular capture in seven episodes, which made overdriving possible, and blocked six episodes of ventricular tachycardia. In no case did transoesophageal atrial pacing lead to an acceleration of ventricular tachycardia or to degeneration into ventricular fibrillation. Transoesophageal atrial pacing can block low-rate sustained ventricular tachycardias (less than or equal to 150 beats per minute). For low rate sustained ventricular tachycardias without haemodynamic impairment, transoesophageal atrial pacing can thus be used as the method of choice thanks to its good ratio of risk to efficiency. PMID- 2210901 TI - Office blood pressures in supine, sitting, and standing positions: correlation with ambulatory blood pressures. AB - The variability of casual (office) blood pressure according to position at the time of measurement was investigated in 168 untreated patients with a history of mild to moderate essential hypertension. Two measurements were made in the supine, sitting, and standing positions on each of 2 consecutive days, and 24 hour ambulatory blood pressure monitoring was performed. The mean supine, sitting, and standing blood pressures were 146 +/- 15/91 +/- 7, 144 +/- 15/96 +/- 8, and 149 +/- 17/103 +/- 7 mm Hg, respectively. Diastolic blood pressures were significantly different from each other (P less than 0.0001). Supine and sitting systolic blood pressures were not different, but they were different from standing blood pressure (P less than 0.0001). The mean of all three positions (overall blood pressure) was 146 +/- 15/96 +/- 7 mm Hg. Supine, sitting, standing, and overall diastolic blood pressure means were 90 mm Hg or more in 88, 133, 164, and 133 patients, respectively. The mean awake ambulatory and 24-hour ambulatory blood pressures were 143 +/- 16/95 +/- 7 and 138 +/- 16/92 +/- 8 mm Hg, respectively, and diastolic blood pressures were 90 mm Hg or more in 121 and 88 patients, respectively. The correlation of office blood pressure with ambulatory blood pressure varied according to office position and was 0.76 to 0.82 (P less than 0.0001) for systolic blood pressure and 0.60 to 0.69 (P less than 0.0001) for diastolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210902 TI - Coronary arterial wall and atherosclerosis in youth (1-20 years): a histologic study in a northern Italian population. AB - Based on the working hypothesis that coronary atherosclerosis begins in childhood, a histologic study was carried out on the subepicardial coronary arterial tree of 100 young persons (1-20 years), who had died from causes unrelated to the cardiovascular system. These subjects were natives of a well defined geographic area in northern Italy, namely the region of Veneto. Intimal proliferations (musculo-elastic and fibro-elastic layers) were observed in 95.3% of the coronary arterial segments in the age group between one and five years. The more distal the coronary segments examined, the lesser was the intimal thickening. Raised mature fibrous plaques were detected in 23 segments from 15 patients (2 from subjects aged between six and 10 years; 4 between 11 and 15 years, and 9 between 16 and 20 years). Single vessel disease was present in 9, double vessel disease in 4 and triple vessel disease in 2 cases. The site most involved by plaques was the proximal part of the left anterior descending coronary artery. Only one plaque was of sufficient dimensions to be considered stenotic (50% luminal reduction). Plaques were rarely sudanophilic, and all seemed to arise in relation to previous intimal thickening. No qualitative nor quantitative sexual differences were observed. These data give rise to much concern, and one consistent with a recently observed occurrence of sudden coronary death in young people from the same geographic area. PMID- 2210903 TI - An arterial duct associated with a congenital anomaly of the coronary arteries: persistence of a murmur after ligation of the duct. AB - A patient is described in whom a persistent murmur was detected after surgical ligation of an arterial duct. Subsequently, she underwent investigation and was found to have associated rare congenital anomalies of a coronary arterial fistula and a single coronary artery. PMID- 2210904 TI - Coronary arteriovenous fistula in tetralogy of Fallot: an unusual association. AB - A congenital coronary arteriovenous fistula is a rare anomaly, and only two cases have been previously reported in association with tetralogy of Fallot. We report one more patient with tetralogy of Fallot who had an associated fistulous communication between the left circumflex coronary artery and the coronary sinus. It is important to localize these left to right shunts preoperatively in order to plan optimal surgical management. PMID- 2210905 TI - Regression of outflow tract obstruction subsequent to treatment with verapamil in hypertrophic obstructive cardiomyopathy. AB - A 29-year-old man suffering from hypertrophic obstructive cardiomyopathy was treated with verapamil 240 mg daily for 4.5 years. During this period the symptoms were reduced, and an intraventricular gradient diminished from 80 to 20 mm Hg, possibly due to a decrease in left ventricular ejection fraction combined with an improved diastolic filling. PMID- 2210906 TI - Characteristics of silent and painful ischaemia during ambulatory monitoring in patients with coronary arterial disease. AB - We compared the characteristics of silent and painful ischaemia during ambulatory ST segment monitoring in 288 patients with documented coronary arterial disease and stable angina. During 12,436 hours of monitoring, 890 ischaemic episodes were recorded, of which 652 (73%) were silent. Silent and painful ischaemic episodes were similar in terms of heart rate at onset of ischaemia, increase in heart rate prior to ischaemia, duration of ischaemia, and percentage of episodes not preceded by an increase in heart rate. Change in the mean maximal ST segment was greater during painful ischaemic episodes (P less than 0.01). Silent ischaemia is characteristically painful ischaemia without the pain. PMID- 2210907 TI - Failure of Doppler ultrasound to detect coarctation of the aorta. AB - Normal velocities of flow in the aortic arch were recorded in a patient presenting with clinical signs of aortic coarctation. Angiography demonstrated complete coarctation with extensive collateral supply to the descending aorta: there was a systolic pressure difference of 40 mm Hg between the ascending and descending segments of the aorta. Despite reports of the value of Doppler ultrasound in the diagnosis of coarctation, the finding of normal velocities of flow within the aortic arch does not necessarily exclude the presence of an obstructive lesion. PMID- 2210908 TI - Pressure-related ventricular tachycardia. AB - A case with syncope on exertion and paced heart block is presented. Non-sustained ventricular tachycardia was seen on Holter monitoring and reproduced repeatedly by either exercise or an injection of an alpha agonist, but not with provocative electrophysiology. Antihypertensive treatment using a beta-blocker with endogenous sympathomimetic activity prevented recurrences. It is suggested that this is a case of pressure-related tachycardia. PMID- 2210909 TI - Aortopulmonary window associated with an anomalous origin of the right coronary artery. PMID- 2210910 TI - The potential of cyclosporin A as an anti-tumour agent. AB - Cyclosporin A (CsA) has become established as the agent of choice for the prevention of organ allograft rejection and has shown considerable promise in the clinical management of certain autoimmune disorders. The impact of CsA as an immunotherapeutic agent of major importance is attributable to its powerful, selective inhibitory action on T-lymphocyte activation and proliferation. Moreover, CsA lacks the myelotoxic and other major side effects associated with cytotoxic immunosuppressive agents, such as cyclophosphamide or azathioprine. It is now clear that CsA has a potential therapeutic role in the treatment of malignancies, especially T-cell cancers. Recent studies suggest that there may be several areas of application for CsA, either as a direct antiproliferative agent or in combination with other drugs, including inhibitors of polyamine biosynthesis or cytotoxic anti-tumour agents, including vincristine and adriamycin. In addition, CsA and non-immunosuppressive analogues have been shown to restore multi-drug sensitivity in cancer cells with acquired drug resistance. A further application of CsA may be to prevent the induction of human immune responses to therapeutic mouse monoclonal antibodies directed against tumour antigens, thereby enhancing the efficiency and safety of this form of cancer immunotherapy. Due to our incomplete understanding of the antiproliferative properties of CsA, further exploration of its potential as an anti-tumour agent must be accompanied by detailed studies aimed at elucidating its action on subcellular molecular events in both normal and malignant cells. PMID- 2210912 TI - Effect of RU 41740 on autologous hemopoietic reconstitution of sublethally irradiated mice. AB - RU 41740, a glyco-protein extract of Klebsiellae pneumoniae 01 K2 strain, is known to have immunomodulator activities. It acts on macrophages as well as on B and T-cells, and enhances their cytokine production, particularly interleukin 1 (IL-1). The fact that cytokines have an effect on hemopoiesis led us to suspect an effect of RU 41740 on hemopoietic reconstitution. In this study, a model of autologous reconstitution of a hemopoietic system after sublethal irradiation in mice was used. C57 BL/6 mice were treated orally with RU 41740 (10 mg/kg/day) before or after irradiation (6.5 Gy). LPS of Klebsiella pneumoniae was used as a positive control. The hemopoietic reconstitution occurred more rapidly in treated animals especially when RU 41740 was given before irradiation. PMID- 2210911 TI - Activation of T-cells by bryostatins: induction of the IL-2 receptor gene transcription and down-modulation of surface receptors. AB - Bryostatins are macrocyclic lactones isolated from the marine bryozoan Bugula neritina. They are currently evaluated for putative antineoplastic activity. Bryostatins bind and activate protein kinase C (PK-C), the cellular receptor for the phorbol ester, and elicit PK-D-dependent cellular functions. Such functions include the expression of the interleukin-2 receptor (IL-2R). Northern blot hybridization with a human IL-2R and an IL-2 cDNA showed that bryostatin 1 (bryo 1), like the phorbol ester, PMA, activates the IL-2R gene. Activation with bryo 1 or PMA in the presence of a calcium ionophore, A23187, increased IL-2 message. These findings indicate that calcium mobilization is necessary for bryo 1 or PMA induced IL-2 gene expression. Unlike PMA, bryo 1 did not cause a vigorous proliferative response of T-lymphocytes unless A23187 was added to the cultures. A bryostatin congener, bryo 13, was inactive in the above assays. Short-term treatment of T-cells with bryo 1 and PMA resulted in an equivalent down regulation of surface CD3 and CD4 receptors without affecting the CD8 receptor. Bryo 1 or PMA mediated expression of surface IL-2R and T-cell proliferation induced by bryo 1 or PMA were sensitive to inhibition by the PK-C antagonists staurosporine (Sts) and H-7. In contrast, CD4 and CD3 down-regulation were resistant to H-7, but could be blocked by Sts, although the Sts concentration required to block bryo 1 or PMA-induced down-modulation was 2.5-fold higher than required to inhibit IL-2R expression and T-cell proliferation. These results indicate that bryostatins activate T-cell through PK-C. PMID- 2210914 TI - Protective effect of saikosaponin A, saikosaponin D and saikogenin D against Pseudomonas aeruginosa infection in mice. AB - Effects of saikosaponins and their genins on nonspecific resistance against Pseudomonas aeruginosa and Listeria monocytogenes infections were investigated. When mice were administered intraperitoneally (i.p.) saikosaponins one day before i.p. infection with P. aeruginosa, saikosaponins a and d induced a marked enhancement of nonspecific resistance at a dose of 10 micrograms/mouse. Also, saikogenin D, a secondary metabolite of saikosaponin d, showed an enhancing effect. The most effective condition for enhancing the nonspecific resistance was i.p. administration of saikosaponin d one day before i.p. or intravenous (i.v.) infection with P. aeruginosa, when mice were treated i.p., i.v., or subcutaneously with saikosaponin d 1, 4 or 7 days previously. Effect of saikosaponin d was weaker than that of formalin-killed bacilli of Propionibacterium acnes and lipopolysaccharide. On the other hand, effect of saikosaponin d on enhancement of nonspecific resistance against L. monocytogenes was not seen. Effector cells participating in the enhanced protection induced by saikosaponin d may be macrophages, since macrophages were a major component in peritoneal cells obtained from mice administered i.p. saikosaponin d 1 day earlier and intracellular bactericidal activity of peritoneal macrophages against P. aeruginosa increased. PMID- 2210913 TI - Immunomodulatory effect of a newly synthesized compound, TOK-8801 (N-(2 phenylethyl)-3,6,6-trimethyl-5,6-dihydroimidazo [2,1-b]thiazole-2-carboxamide) on antibody production in vivo and delayed-type hypersensitivity in mice. AB - The immunopharmacological effects of a newly synthesized compound in vivo, TOK 8801 (N-(2-phenylethyl)-3,6,6-trimethyl-5,6-dihydroimidazo[2,1-b]thi azo le-2- carboxamide), on the anti-SRBC plaque-forming cell (PFC) response and delayed type hypersensitivity (DTH) reaction were investigated. Oral administration of TOK-8801 (0.1-10 mg/kg) resulted in the suppression of the PFC responses to varying doses of antigen (5 x 10(6), 2 x 10(7), 1 x 10(8)) in C3H/He strain mice (7 W) which are high responders to SRBC antigen. On the other hand, the compound augmented the PFC response in aged mice (8-9 months) in which the PFC response was markedly depressed compared with that in young mice. In the experiment of the methylated human serum albumin-induced DTH reaction, TOK-8801 augmented the reaction in low responder (C57BL/6) mice by oral administrations of 0.1-1 mg/kg for 5 days from the sensitization, whereas suppressed the reaction in high responder (ICR) mice. These immunopharmacological actions of TOK-8801 were compared in dose and activity with those of lobenzarit and bucillamine. Thus, these results suggest that TOK-8801 may act as an immunomodulating agent and would be expected to be a useful agent for autoimmune diseases such as rheumatoid arthritis. PMID- 2210915 TI - Modulation of polyclonal activation of lymphocytes by cyclophosphazenic compounds bearing ethylene-imino groups and vectorized by polyamines. AB - Cyclophosphazenic compounds bearing ethylene-imino groups are cytocydal chemicals which can modulate polyclonal activation of lymphocytes (PAL) and prevent the development of murine lupus. The effects on PAL of the different parts of these chemicals and of vectorization by polyamines have been investigated by treating lipopolysaccharide injected C57Bl/6 mice with various cyclophosphazenic compounds and thiotepa. The immune effects of the cyclophosphazenic substances have been found to be mediated by ethylene-imino groups and to be modulated by polyamine vectorization. These compounds might represent a new class of drugs for treatment of immune mediated diseases of the lupus type. PMID- 2210916 TI - Loss of limb regenerative capacity during postmetamorphic growth in the tree frog, Hyla arborea japonica. AB - Anuran limb regenerative capacity was investigated in froglets of various sizes (snout-vent length) and adults of the Japanese tree frog, Hyla arborea japonica by amputating forelimbs through the zeugopodium and stylopodium. Almost all limbs amputated through the zeugopodium showed heteromorphic regeneration in postmetamorphic froglets 14 to 18 mm in length. However, the larger the froglet, the lower the capacity of limb regeneration. Regenerative capacity was completely lost in adults of more than about 30 mm in length. When froglet and adult limbs were amputated through the stylopodium, no signs of limb regeneration were observed. Complete denervation of limb stumps resulted in no regeneration in all cases examined. When partial denervation was performed on limbs amputated through the zeugopodium, there were signs of regeneration in the presence of the remaining nerves, but this was limited to very young froglets. Nevertheless, the regenerates obtained were limited in gross structure compared with normal limb regenerates. However, when the nerve supply to the distal forelimb was augmented by surgically diverting ipsilateral sciatic nerve bundles, the limbs of normally nonregenerating adults regenerated after amputation through the zeugopodium. Furthermore, normally nonregenerating limbs amputated through the stylopodium also regained a limited regenerative capacity, if supported by an ipsilaterally augmented nerve. These results show that the loss of limb regenerative capacity in Hyla arborea japonica during postmetamorphic growth is caused by a deficiency in the quantity of innervation. PMID- 2210917 TI - Brain and body growth and allometry in the Mongolian gerbil (Meriones unguiculatus). AB - A new four-parameter version of Putter's curve (Putter, 1920), recently developed by Jolicoeur and Pirlot (1988), is applied to cross-sectional data on brain and body growth in 127 male and 136 female Mongolian gerbils (Meriones unguiculatus) ranging from birth up to approximately 2 years in postnatal age. The physical development of the gerbil is more rapid than that of the white rat and of the domestic rabbit even though its behavioral development is known to be somewhat slower. Like other recent studies on rats, rabbits and humans, the present analysis indicates that complex allometry (curvature of log-log relationships) is more widespread in the quantitative development of mammals than generally realized. PMID- 2210918 TI - Natural selection and the endocrinology of prostatic cancer: aging's debts from a fit youth. PMID- 2210919 TI - Thymidine and somatomedin-like activity of fetal pig sera: effect of fetal decapitation. AB - The effect of fetal decapitation on porcine serum thymidine and somatomedin activity was studied. Fetal decapitation, at 45 d of gestation, did not alter body weight when compared to controls at 110 d of gestation. Thymidine activity, measured as 3H-thymidine incorporation into rat L6 myoblasts in response to test sera, did not differ between decapitated (D) and control (C) fetal pig sera. Thymidine activity of fetal sera was low when compared to a postnatal normal pig serum pool (NPS) and approximately equal to that of a postnatal hypophysectomized pig serum pool (HPS). Somatomedin-like activity, measured as 35S-sulfate uptake into 110 d fetal costal cartilage, was similar in D and C sera and was low when compared to NPS. Postnatal cartilage, but not fetal cartilage, responded greater to NPS than to HPS when measuring somatomedin activity. This indicates that fetal cartilage may be sensitive to different factors than postnatal pig cartilage. Thymidine activity and somatomedin-like activity were also low in maternal sera when compared to NPS. The concentration of insulin-like growth factor-I (IGF-I) was lower in D sera when compared to C sera (0.26 +/- 0.03 vs 0.62 +/- 0.09 U/ml, respectively, p less than 0.05). It is postulated that locally produced growth factors, compared to circulating growth factors, may be more important determinants controlling the rapid growth rate of the fetus. PMID- 2210920 TI - Light deprivation retards the growth of the diethylstilbesterol-induced renal tumor in hamsters. AB - Chronic treatment with diethylstilbesterol (DES) induces renal cancer in male Syrian hamsters. This tumor may result from direct carcinogenicity of the estrogen, but extrarenal neuroendocrine effects of DES may also be important in modulating tumor growth in the kidney. Since light deprivation is known to profoundly influence neuroendocrine function in the hamster, we elected to examine the effects of short photoperiod or blinding on the development of the DES-induced renal tumor in this species. Animals were maintained either in long (14 hours of light and 10 hours of dark) or short (10 hours of light and 14 hours of dark) photoperiod or blinded. Groups of six to eight animals were sacrificed after three, six or nine months of treatment with either DES or the vehicle. All animals treated with DES for nine months had evidence of renal tumors, but the rate of growth and final size of the tumors were significantly reduced by either maintenance in short photoperiod or blinding. These data provide unique evidence of the importance of neuroendocrine system in the modulation of the DES-induced renal tumor in hamsters. PMID- 2210921 TI - The measurement of milk intake in the neonatal guinea pig. AB - Study of the effects of enteral nutrition on neonatal growth and development has been hindered by lack of a suitable model. An isotope dilution method for the measurement of milk intake in suckling rodents was evaluated in 13 hand-fed neonatal guinea pigs, by comparing milk intakes determined using 3H20 with intakes determined by difference in weight before and after feeding. The effects of two experimental durations (1 or 2-3 days) on the accuracy and precision of the method was assessed. Weighted milk intakes were 18 -26 g/day, and body weight changes were -7% - +12% of initial weight. There was no significant difference between milk intakes determined using the two methods for both 1 and 2-3 day comparisons. However, the coefficients of variation for 1 and 2-3 day measurements were 24.4% and 5.5%, respectively. These values are equivalent to precisions of approximately 10% and 2% for estimates of total milk output in a rodent suckling 8 pups. It is concluded that the 3H20 method is no less accurate or precise than the weighing method for 2-3 day measurements of milk intake in individual pups and milk production of dams. These findings strengthen the use of the precocial guinea pig as a model for the study of the effects of early feeding on growth, development and aging. PMID- 2210922 TI - Stimulation of food intake and growth of swine by cholecystokinin immunization. AB - Experimental superalimentation at 30% above ad libitum intake increased growth 40% and confirmed that voluntary food intake is a growth-limiting factor in swine. A sequence of contingent hypotheses was proposed for swine: cholecystokinin (CCK) is a regulator of food intake; food intake is enhanced by reduction of serum CCK; serum CCK is reduced by anti-CCK antibodies: anti-CCK antibodies are raised by active immunization. The objectives of this study were to determine if antibodies were raised in immunized swine and if the anti-CCK titers were sufficient to increase food intake and growth. Twelve young growing swine were immunized against cholecystokinin (CCK-8) to test the hypothesis that anticholecystokinin antibodies in serum would suppress cholecystokinin inhibition of appetite (food intake). An equal number of control animals (hSG) were immunized against the antigenic carrier protein by the same protocol. Specific binding of [125I]CCK-8, the C-terminal octapeptide, by sera diluted 1:181 increased to a peak value on day 43. Food intake and body weight gain were similar for the two groups during the first phase of the study. However, food intake was 8.2% greater and body weight gain was 10.6% greater for the CCK-8 than for the hSG group during the second phase (d 43 to d 77). Total food intake over the 77-day study was 5.4% greater for the CCK-8 group (P = .08): body weight gain was 8.3% greater (P = .006). Regression analyses confirmed that gain over the 34 day second phase increased .076 kg (P = .045; R2 = 0.34) for each percentage unit increase of serum binding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210924 TI - Intoxication and criminal responsibility. PMID- 2210923 TI - Should mice be selected for postponed aging? PMID- 2210925 TI - Intoxication, criminality, and responsibility. PMID- 2210926 TI - Alcoholism, freedom, and moral responsibility. PMID- 2210927 TI - Medicalization and regulation of alcohol and alcoholism: the professions and disciplinary measures. PMID- 2210928 TI - Governing images of alcoholism in Germany, 1870-1920. PMID- 2210930 TI - The taint of intoxication. PMID- 2210931 TI - Nosologic objections to the criminal defense of pathological intoxication: what do the doubters doubt? PMID- 2210932 TI - Alcoholism: can honest mistake about one's capacity for self control be an excuse? PMID- 2210933 TI - Intoxication and responsibility. PMID- 2210934 TI - Does addiction excuse thieves and killers from criminal responsibility? PMID- 2210935 TI - Parasitological serendipity: from Schistocephalus to Echinococcus. AB - Attention is drawn to the situation nowadays, whereby workers are encouraged to undertake research which appears useful or of economic importance, although the History of Science indicates that many major discoveries have been the result of 'serendipity'--'the chance observation falling on the receptive eye'. Some of the more important examples in Medicine and Parasitology are reviewed. The author then relates how he was given a stickleback infected with the plerocercoid of Schistocephalus solidus, an episode which eventually led to the successful in vitro culture of the adult of this species. Attention is also drawn to the largely unrecognized work of the Danish Veterinarian, P. C. Abildgaard, who in 1789 demonstrated that this species completed its life cycle in a bird, thus establishing, for the first time, the transmission of a parasite from one host to another. The in vitro culture of S. solidus led to the development of successful in vitro techniques for Ligula intestinalis and for Echinococcus granulosus and E. multilocularis. The observation that E. granulosus of horse origin failed to grow in vitro led eventually to the concept of physiological 'strains' of E. granulosus, now a subject of much international research. PMID- 2210936 TI - Australian Society for Parasitology. Proceedings of the silver jubilee scientific and general meeting. Magnetic Island, Townsville, September 26-29, 1989. PMID- 2210937 TI - The Bancroft-Mackerras oration. The changing face of science. PMID- 2210938 TI - Australasian contributions to an understanding of the epidemiology and control of hydatid disease caused by Echinococcus granulosus--past, present and future. AB - For several years after Echinococcus granulosus was introduced into Australasia from Europe, its life cycle was unknown. Before the end of the 19th century, however, Cystic Hydatid Disease (CHD) was recognized in humans as an important cause of death, although its magnitude was not quantified. During the first 50 years of the 20th century, the urban component declined, but CHD remained a serious source of ill-health. During the second half of the 20th century major research contributions have included: (i) differentiation of pastoral from wildlife Echinococcus and (ii) breaking the 'epidemiological code' of the family Taeniidae, thereby defining the conditions under which transmission occurs. Based on this research and concurrent surveys, it is concluded that the present geographical distribution of E. granulosus in domestic animals and CHD in the rural population is determined by climate; being uncommon where hot dry seasons continue beyond a few months. The parasite's range may be extended in its wildlife cycle through a highly susceptible definitive host--the dingo. The ease with which blowflies transfer taeniid eggs from dog faeces to animal and human foodstuffs implies that in Australasia, CHD can sometimes be regarded as foodborne. A perceived decline in autochthonus cases in the rural community during the second half of the 20th century may be accounted for by increased standards of living generated by economic advancement. Where a decline has not occurred or incidence is unusually high, CHD may be acting as an indicator of social disadvantage. Field trials and control programmes demonstrated that pastoral echinococcosis readily responded to intervention. Indeed, in both New Zealand and Tasmania, using different administrative structures and methods of funding, E. granulosus was driven from endemic towards extinction status. The really convincing result was the rapid decline in CHD in all age groups. The problem still to be solved is to identify methods for eliminating foci where high levels of CHD still exist but, continent- or even state-wide intervention may not be considered to be cost-effective using current tools. Here, mathematical modelling and cost-benefit analysis can be regarded as powerful methods to assist the decision-making process. PMID- 2210939 TI - Echinococcus: biology and strain variation. AB - Biology and strain variation in the causative agent of hydatid disease is reviewed with emphasis on developmental and genetic aspects. In vitro cultivation experiments have made a significant contribution to current knowledge of the developmental plasticity of Echinococcus. However, the mechanisms which regulate and determine developmental strategies in the parasite, as well as the characteristics, source and cytodifferentiation of germinal cells, are not understood. The nature, significance and origin of strain variation in Echinococcus are examined. Before we can fully appreciate the phenotypic consequences of genetic differentiation between populations, we need to know something about the genetic and environmental components of variation in traits such as development rate, host preference, host specificity, virulence and drug resistance. There is an urgent need for research on the developmental pathways by which genetic differences within and between strains of E. granulosus are translated to phenotypic differences in these traits. PMID- 2210940 TI - Immunology and molecular biology of Echinococcus infections. AB - Echinococcus spp. are the etiological agents of hydatid disease in man and other intermediate hosts. Many questions regarding the factors which determine susceptibility/resistance to hydatid disease, and the factors which influence the viability and fertility of hydatid cysts, remain to be answered. Recent research into the effects of hydatid infection on the immune system of the host has provided some insights into the host-parasite relationships. Immunochemical and recombinant DNA techniques are being applied to improve diagnosis of hydatidosis in man and E. granulosus infection in dogs, and also in the development of vaccines against infection with taeniid cestode larvae. The successes which have been achieved in these areas are likely to provide valuable tools for the control of cystic hydatidosis in man. These recent studies in the areas of immunobiology, serological diagnosis and vaccination are reviewed. PMID- 2210941 TI - Changing approaches to the study of Giardia epidemiology: 1681-2000. AB - Since the first description of Giardia by Antony van Leeuwenhoek in 1681, this parasite has proved to be enigmatic with a much more complicated epidemiology than originally envisaged. Even the nomenclature of this organism is confused. Despite numerous community prevalence studies, it was not until 1970 that the first proven report of waterborne transmission occurred. In 1981 the first common source outbreak due to contaminated food was recorded. It is also now recognized that venereal transmission occurs, especially among homosexual males. The faecal oral route still remains the most important mode of infection despite the elucidation of these other methods of transmission. Recent developments in molecular biology especially DNA 'fingerprinting' and karyotyping which allow individual strain identification are being used to answer key epidemiological questions; for example are there truly pathogenic strains of Giardia, does drug resistance develop in vivo and is giardiasis a zoonotic disease? These and other molecular biological approaches will form the basis of research into the epidemiology of giardiasis and other intestinal protozoal infections until the end of the century and are certain to hold many surprises. PMID- 2210942 TI - Drug resistance in Giardia intestinalis. AB - Evidence for drug resistance in giardiasis is reviewed and biochemical studies undertaken to determine the basis for this resistance are discussed. Metronidazole and furazolidone, which produce toxic radicals within the cell, have different biochemical mechanisms of action. Resistance to metronidazole is negatively correlated with the intracellular concentration of pyruvateferredoxin oxidoreductase leading to a concomitant decrease in the uptake of free metronidazole into the cell, while resistance to furazolidone appears to be due to an increase in thiol cycling enzymes. At the molecular level resistance to metronidazole is associated with DNA changes. DNA probes which hybridize with specific chromosomes and repetitive sequences indicate that rearrangements both at the chromosome and repetitive DNA level occurred concurrently with the development of metronidazole resistance. The problems of cross-resistance and treatment failures that occur in the absence of resistance are additional difficulties which have important implications for the management of individual patients. New drugs such as azithromycin, while showing great variation in activity against different stocks may be useful in treating some refractory cases of giardiasis. In the community, it is important to recognize the occurrence and spread of drug resistant Giardia, and markers, such as DNA probes, provide methods to monitor potential epidemics and the spread of drug resistant Giardia. PMID- 2210943 TI - Human immune responses against sexual stages of malaria parasites: considerations for malaria vaccines. AB - Studies on the natural immune responses to the sexual stages of malaria parasites have been reviewed in the context of human malaria transmission-blocking vaccines. Antibodies against the sexual stages of the malaria parasite, gametocytes and gametes, are readily evoked by natural malaria infections. These antibodies that suppress infectivity at high concentrations can, at low concentrations, enhance the development of the parasite in the mosquito; however, because enhancing antibodies are prevalent during natural malaria infections, it is likely that a vaccine would rapidly boost these antibodies to blocking levels. The immunogenicity of sexual stage antigens appears to be constrained in the human host, probably due to T epitope polymorphism and MHC restriction in humans. These constraints apply mainly to those antigens that are sensitive targets of host immunity such as the gamete surface antigens and not to internal gamete antigens, indicating that antigenic polymorphism may have evolved in response to immune selection pressure. Evidence for immunosuppression of the host by exposure to endemic malaria is presented and its consequences on vaccine development are discussed. PMID- 2210944 TI - Chemotherapy and drug resistance in malaria. AB - Over recent years many antimalarial drugs have been rendered useless by the development of resistance by the malaria parasite. New antimalarials are rapidly suffering the same fate as the traditional therapies and yet a biological understanding of the mechanisms of resistance has, until recently, not been described. This review describes recent work which has identified the mechanism of resistance to the dihydrofolate reductase (DHFR) inhibitors as being due to point mutations within the DHFR gene that render the enzyme less susceptible to inhibition by the drugs. The relationship between chloroquine resistance and the recently described multidrug resistance gene is explored and the possibility that this is the main cause of chloroquine resistance by the parasite is discussed. Parasites have developed resistance against many of the quinine-like antimalarials over the past three decades and the possibility that this is linked to the appearance of chloroquine resistance must be considered. PMID- 2210945 TI - Anthelmintic resistance in nematodes: extent, recent understanding and future directions for control and research. AB - Resistance has now been reported to all of the broad spectrum anthelmintic types currently available, namely to the benzimidazoles, levamisole/morantel and to ivermectin. The problem causes most concern for parasite control in sheep, but anthelmintic resistance has also been reported in nematodes of horses, goats, pigs and more recently cattle. Our understanding of the factors which select rapidly for resistance has increased and programmes of worm control which minimize selection for anthelmintic resistance are being developed and tested. One of the greatest problems encountered in attempting to reduce the selection for overt drug resistance is the need for more sensitive tests for developing resistance. In the long term, new approaches to chemotherapy and to overcoming anthelmintic resistance problems will arise from improving our understanding of the modes of action of, and mechanisms of resistance to, anthelmintics at the level of the receptor proteins and their genes. PMID- 2210946 TI - Prospects for the control of sheep blowfly strike by vaccination. AB - Research into vaccination against flystrike is aimed at either controlling the predisposing condition, fleece rot, or direct control of the fly maggots. A vaccine against the major bacterial species found in fleece rot lesions, Pseudomonas aeruginosa, is undergoing field trials and results suggest that this vaccine may reduce fleece rot incidence. Problems to be investigated include the existence of variants of P. aeruginosa in the field and the involvement of other species of bacteria in fleece rot. Strategies for direct vaccination include immunization with larval products involved in wound formation and larval nutrition and immunization against novel antigens usually from the gut of first instar larvae. Both methods have resulted in significant inhibition of larval growth. Analysis of larval products has revealed a number of active proteases which degrade skin proteins such as collagen. Inhibition of these enzymes with plasma enzyme inhibitors also affects larval growth in vitro. Antibodies raised against these enzymes are being tested for inhibitory effects against larvae and used to isolate cDNA clones from Lucilia cuprina libraries. Antigens from the gut are able to induce antibodies inhibitory to larval growth both in vitro and in vivo. Isolation of these antigens is proceeding in a number of laboratories. Problems still to be analysed include whether growth inhibition produces effective protection in the field and whether sufficient antibody will have early access to the larvae to significantly affect them. PMID- 2210948 TI - Marine parasites: an Australian perspective. AB - A review is given of major studies in marine parasitology in Australia. Aspects discussed include: geographical distribution of parasites in Australian coastal waters and their affinities to parasites of other zoogeographical regions; species diversity in Australian coastal surface and deep waters; use of marine parasites for stock discrimination; use of marine parasites as ecological models; ultrastructural and phylogenetic studies of marine parasites; and effects of marine parasites on their hosts. PMID- 2210947 TI - The role of helminths in the biological control of mammals. AB - Biological control of invertebrates has been successful while that of vertebrates has been, with the exception of myxomatosis in rabbits, unsuccessful; reasons for this are discussed. Demographic studies of small mammals suggest that population regulation occurs by several different mechanisms, more than one of which may be acting at the same time. Coevolution is an important phenomenon in host-parasite associations, nevertheless parasites may limit host population abundance. The basis of the regulatory effect on the host population is that parasite-induced host mortality or reduction in fecundity is density-dependent. Increasing evidence of the density-dependent effects of helminths on host survival and reproduction is forthcoming from laboratory studies but has not been confirmed in the field. The theory that a helminth parasite may regulate mammal population abundance has been verified recently in the laboratory. A multidisciplinary research programme aimed at understanding the mechanisms responsible for formation of house mouse (Mus domesticus) plagues and seeking strategies to reduce mouse numbers is discussed. One aspect of the work involves investigation of the potential of the nematode, Capillaria hepatica, as a biological agent in the control of wild mice in the cereal-growing regions of Australia. Biological control of mammals is viewed within the context of integrated pest management. A helminth species which reduces host survival or fecundity at an increasing rate as host abundance increases has a role in host population regulation. There is potential to capitalize on that role and apply the helminth as a biological agent in the control of mammals which have attained pest status. PMID- 2210949 TI - Studies of respiratory stridor in young children: acoustical analyses and tests of a theoretical model. AB - Non-invasive procedures are proposed to aid the diagnosis of childhood laryngotracheal pathology and to monitor the course of such disease. The procedures capitalize on the one-to-one relationship which exists between the acoustic phenomena (stridors) associated with respiration and the configuration of the respiratory tract. Careful analysis of these acoustic patterns can thus assist in identifying and localizing constrictions, in diagnosis, and in monitoring disease severity. Based on the acoustical analysis of the stridor generated by children with congenital stridor, subglottal laryngitis, and trachea stenosis, the present paper demonstrates that a close relationship exists between the specific pathology and the spectrum of the associated respiratory stridor. PMID- 2210950 TI - Airway compromise from nasal obstruction in neonates and infants. AB - Nasal obstruction in neonates can cause significant airway compromise and even be life-threatening. In general, otolaryngologists are familiar with management of the neonate born with choanal atresia but there have been few reports and there are no guidelines for management of the neonate or young infant who presents with nasal obstruction and airway compromise but who does not have choanal atresia (NOWCA). This study demonstrates the difficulty in diagnosis, variability in severity of airway compromise, and delineates the problematic aspects of management. PMID- 2210951 TI - Tympanometric screening in children on admission to a paediatric ward: a preliminary study. AB - Tympanometric screening of children admitted to paediatric wards has not previously been undertaken. In order to describe the middle ear status and to estimate the point prevalence of middle ear effusion (MEE) in this population a preliminary study based on a single tympanometry test was undertaken. MEE was defined by the finding of a flat curve in the tympanogram of at least one ear. 601 children were admitted during the study period. 427 (71%) entered the study and this group was representative of the total population that was referred. 82% were found to have an abnormal middle ear pressure and MEE was diagnosed in 59% of the children. 76% of the children were 0- to 4-year-olds. 31% were admitted due to respiratory infections and 41% presented with catarrhalic symptoms. MEE was associated with the age group of 0- to 4-year-olds and with the presence of catarrhalic symptoms. The population of paediatric in-patients represents the highest frequency of abnormal tympanometry findings hitherto reported. It should be emphasized that the one-time finding of a flat tympanogram does have the correlation but no congruence with MEE and the finding of this high prevalence of MEE needs to be followed up by studies using independent methods for confirmation of the middle ear fluid. PMID- 2210952 TI - Facial nerve paresis as the presenting symptom of leukemia. AB - Leukemic involvement of the temporal bone is not uncommon and may present in a variety of ways including auricular or external canal skin lesions, red or thick tympanic membrane, middle ear effusions, otitis media, hearing loss or mastoiditis. Symptomatic facial nerve involvement, on the other hand, is extremely unusual. We discuss a pediatric patient whose sudden onset facial nerve paresis was the presenting symptom that led to her diagnosis of leukemia. At the time of mastoidectomy, a granulocytic sarcoma or chloroma was noted to be overlying the VIIth nerve. PMID- 2210953 TI - Ectodermal dysplasia: the otolaryngologic manifestations and management. AB - Ectodermal dysplasia is a rare group of diseases presenting special problems in management for the otolaryngologist, but the full spectrum of otorhinolaryngologic manifestations has been previously unrecognized in the otolaryngologic literature. The anhidrotic form, characterized by deficient sweating, sparse hair growth and deficient teeth, with associated decreased mucous production in the aerodigestive tract leads to chronic upper respiratory tract infections, otitis, dysphagia, hoarseness, bronchitis and sometimes hemoptysis. PMID- 2210954 TI - Juvenile myasthenia gravis: an unusual presentation. AB - Myasthenia gravis is a disease characterized by muscular weakness and fatigability which afflicts 2-10 patients per 100,000 with 20% of cases presenting in childhood. Muscles innervated by cranial nerves are frequently involved with ptosis and diplopia being the most frequent presenting complaints. We review the literature and report a case of a 20-month-old infant presenting with inspiratory stridor and cyanosis, resembling foreign body aspiration. PMID- 2210955 TI - Immediate correction of congenital nasal deformities; follow-up of 8 years. AB - A total of 4724 newborns was screened for congenital nasal deformities. Altogether 91 (1.9%) pathological, screening-positive cases were found. Because of refusal to participate, 3 pathological cases were lost leaving 88 cases. The first 55 screening positive newborns were left without treatment while an attempt was made by an otolaryngologist to correct the remaining 33 cases within a week from delivery. Eighty-two newborns of those who passed the screening tests were analyzed as a control group. In 1987, at the age of 8 years the case and control children were interviewed by mailed questionnaire and invited to be re-examined by an ENT-surgeon. Forty-seven of the not corrected, 21 of the corrected cases and 61 controls came to the re-examination. The luxated septal cauda tended to be straight both spontaneously as well as after active treatment. The few mid-septal pathologies (vomerine junction) in the corrected group were resistant to the treatment attempted. The mid-septal deformities found in the follow-up were connected with frequent antibiotic prescriptions but not respiratory infections. No increase in frequency of otitis media or sinusitis was noticed. The immediate treatment of nasal deformities did not significantly affect the clinical status of the nose at the follow-up. Thus the benefit of immediate treatment on nasal deformities in newborns and screening to find them remains questionable. PMID- 2210956 TI - Laryngeal leiomyoma. AB - A case of leiomyoma arising from the subglottic area of a child is reported. This neoplasm is extremely rare in the larynx as only 14 cases have been described in the literature so far. Only 4 of these could be defined as subglottic. The clinical and histopathological features of laryngeal leiomyomas are briefly discussed. PMID- 2210957 TI - Surgical management of congenital supraglottic lateral saccular cyst. AB - A case is described of a neonate with a rare, congenital, supraglottic, lateral, saccular cyst presenting with stridor and asphyxia. Repeated needle aspirations of the cyst failed to provide sustained clinical improvement. CT scans proved useful for precise intralaryngeal location of the cyst and planning of the surgical excision. At two months of age the cyst was successfully excised by a paramedian thyrotomy via an external cervical approach, avoiding tracheostomy. PMID- 2210958 TI - Vitamin E status of Congolese children in a rural area. AB - The role of vitamin E in severe malnutrition is controversially discussed. In order to evaluate the vitamin E status of unselected African children the plasma tocopherol levels of 52 children from a village in the People's Republic of Congo were assessed by HPLC and related to the plasma lipid values. Although plasma concentrations of total tocopherols (mean 351.1 +/- 59.4 micrograms/dl) and alpha tocopherol (mean 313.3 +/- 57.0 micrograms/dl) were found to be low, normal ratios of total tocopherols to total lipids (mean 0.99 +/- 0.17 mg/g) and alpha tocopherol to total lipids (mean 0.89 +/- 0.09 mg/g) were estimated. It is concluded that plasma vitamin E levels should be related to plasma lipids if populations are monitored in which low lipid concentrations have to be expected. These data on Congolese children may be used for comparison if the vitamin E status in other agrogeographical areas of Africa or in clinically abnormal groups is investigated. PMID- 2210959 TI - The relationship between the thiamin pyrophosphate effect and the saturation status of the transketolase with its coenzyme in human erythrocytes. AB - The thiamin pyrophosphate effect has been used as a reliable index to evaluate the nutritional status of thiamin. But there has not been any report concerning whether or not the thiamin pyrophosphate effect really reflects the saturation status of transketolase with thiamin pyrophosphate. In this report we studied the relationship between the thiamin pyrophosphate effect and the saturation status of transketolase. First, we determined the thiamin pyrophosphate concentrations, transketolase activities, thiamin pyrophosphate effects, and transketolase concentrations in human hemolysates from 16 apparently healthy subjects. The molar ratio of thiamin pyrophosphate to transketolase was in inverse proportion to the thiamin pyrophosphate effect. Second, we prepared apotransketolase preparations and reconstituted it with various concentrations of thiamin pyrophosphate. The thiamin pyrophosphate effects in these preparations were in good correspondence with the ratios of apotransketolase. These results indicate that the thiamin pyrophosphate effect really reflects the saturation status of transketolase with coenzyme. PMID- 2210961 TI - Clinical chemical methods for the routine assessment of the vitamin status in human populations. Part III: The apoenzyme stimulation tests for vitamin B1, B2 and B6 adapted to the Cobas-Bio analyzer. AB - The programming of the Cobas-Bio centrifugal analyzer for kinetic tests of transketolase, glutathione reductase and aspartate amino-transferase is described. The results obtained in a population of 200 healthy people of both sexes are reported. PMID- 2210960 TI - Levels of minerals in serum and urine of guinea pigs following intraperitoneal administration of ascorbate. AB - The effect of ascorbic acid administration on the levels of urinary and serum mineral nutrients, Ca, Cu, Fe, K, Mg, Mn, Na and Zn in guinea pigs has been studied. Male guinea pigs received sodium ascorbate solution (equivalent to 1 g ascorbic acid/kg body weight/day) by intraperitoneal injection for 4 weeks. During the ascorbic acid treatment period, serum and urinary ascorbic acid rose markedly. The large quantities of ascorbic acid intake did not influence serum levels of all eight minerals studied when experimental values were compared with controls using the two-tailed Student's t-test. However, when the one-tailed t test was used, serum copper and zinc levels of the experimental guinea pigs were significantly lower than their respective control values. Excepting sodium, derived from injected sodium ascorbate, no differences in daily urinary excretion of the other seven minerals were observed. PMID- 2210962 TI - Interrelationship between serum concentrations of methionine, vitamin B12 and folate. AB - The metabolism and intracellular recycling of methionine requires vitamin B12 as cofactor and methyltetrahydrofolate as coreactant. To examine the interrelationship between serum levels of methionine, vitamin B12 and folate, serum methionine levels were assayed in patients with reduced levels of these vitamins and in healthy subjects. Approximately half the patients with either vitamin B12 or folate deficiency, and more than half those with combined deficiency, had methionine levels below the reference range (37-136 mumol/l). There was no correlation between vitamin B12 or folate and serum methionine levels within the healthy group. There was also no correlation within the group with low folate levels. Within the vitamin B12 deficient group on the other hand, the correlation was highly significant (r = 0.547, p less than 0.001). The finding that many patients with vitamin B12 or folate deficiency have normal serum levels of methionine suggests a significant role for other factors such as betaine-dependent methionine synthesis in the maintenance of serum methionine concentrations. PMID- 2210963 TI - Effect of dietary eicosapentaenoic acid on plasma lipids and platelet function in stroke-prone spontaneously hypertensive rat. AB - An investigation was undertaken to study the effect of EPA in rats fed different protein sources. A highly concentrated EPA (78% EPA, ethyl ester form), manufactured from sardine oil was administered to SHRSP (Stroke-prone spontaneously hypertensive rat) and WKY (Wistar Kyoto) for 4 weeks. Casein or SPI (soy protein isolate) was used as protein source in the experimental diet. In the experiment concerning casein diet, showing significant decrease in systolic blood pressure, plasma lipids of SHRSP were observed after EPA treatment, but no significant difference was found in SPI diet group. Although there was no significant change in systolic blood pressure of WKY after EPA treatment, a similar effect of EPA on plasma lipids level and platelet aggregation were also observed in WKY. However, supplementing methionine to SPI diet induced the reducing effect of EPA in rats. In addition, higher level ratios of EPA to arachidonic acid were observed in the plasma and platelets of rats fed SPI diet containing methionine supplement when compared with rats fed SPI diet. It was suggested that the amino acid profile was related to the effective utilization of EPA in rats. PMID- 2210964 TI - Iron deficiency risk in children: discrepancy between dietary and biochemical assessments. AB - A random sample group of 300 children and adolescents (aged 0.5 to 16 years) from a Mediterranean town of Spain, were investigated as part of a health education program. Analysis of dietary iron intake and the biochemical parameters of iron status (red cell volume, erythrocyte protoporphyrin concentration, transferrin saturation percentage and serum ferritin) were measured. Based on dietary assessment, the percentage of children with iron intake levels below the Catalonia Recommended Daily Amounts varied from 24% to 77% and showed age and sex differences. The percentage of children with iron intakes below their own individual requirements varied between 7% and 41%. The age groups with the highest risk of iron deficiency were girls aged between 6 and 24 months, and boys aged between 13 and 16 years. However, based on the biochemically assessed iron status, the results revealed an overall prevalence of iron deficiency varying from 0 to 23.3%. The highest prevalence was encountered in boys and girls between 6 and 24 months (23.3%), compared with only 3.3% between 13 and 16 years. Despite conducting the investigation with the recommended controlled methodology, the results from dietary assessed risk of iron deficiency were significantly different from those assessed biochemically. Hence, caution is required when designing health programme strategies based exclusively on nutritional intake assessments. PMID- 2210965 TI - Hepatic selenium concentration in pigs with microangiopathy (mulberry heart disease)--an animal model for the study of oxidative damage. AB - The significance of selenium deficiency was investigated in pigs that died suddenly of microangiopathy (MAP, mulberry heart disease). Hepatic selenium concentration (mean +/- SD) in pigs with MAP (1.04 +/- 0.47 micrograms/g dry weight) was lower than in healthy pigs (1.23 +/- 0.53 micrograms/g). The lowest hepatic selenium values were found in pigs with MAP and in 22.2% of MAP pigs hepatic selenium concentration was below 0.5 microgram/g which reflects selenium deficiency. Thus, pigs with a low selenium status are at risk of MAP. The low selenium status together with vitamin E deficiency increases oxidative stress and thus contributes to the development of oxidative damage. PMID- 2210966 TI - Relationship between zinc and cellulose intakes in growing rats. AB - We have studied the effect of cellulose on the intestinal absorption of zinc and its metabolism with weanling male rats. Experimental diets were cellulose (5, 8 or 20%) and noncellulose containing normal zinc (AIN-76 mineral mix., 3.0 mg%) or high zinc (10 times of normal, 30 mg%). Weanling rats fed on these diets ad libitum for 16-42 days. There were no significant differences between noncellulose-feeding and cellulose-feeding groups in body weight gain or protein and DNA concentrations in the liver. The inhibitory effect of 20% cellulose on zinc absorption was observed in the long term experiment, as the concentrations of plasma zinc of the group receiving 20% cellulose were decreased significantly more than that of noncellulose-feeding group. PMID- 2210967 TI - 8th European Fat Soluble Vitamins Group Meeting. Leeds, U.K., March, 1990. Abstracts. PMID- 2210968 TI - Plasma fibronectin: a study of 340 assays. AB - The authors report the results of 322 assays of plasma fibronectin. The object of this study was to specify its diagnostic contribution. The assays have been effected from February 1987 to October 1988 by the laser nephelometric method in all the hospitalized patients without exclusion. We have defined two populations on clinical diagnostic criteria into 193 control cases and 129 patients suffering from inflammatory rheumatisms or bone neoplasias. The statistical processing has been effected in the Department of Medical Computer Science. The results are as follows: The rate of plasma fibronectin is inclined to increase with age (p = 1 X 10(-4) a little higher among men than among women (p = 0.05). With regard to the other biological markers of inflammation, there was no obvious correlation with the rate of fibrin, the sedimentation rate at the first hour, or the presence of C-reactive protein. This study does not confirm the specificity of this assay in the inflammatory rheumatisms although our two populations are strictly comparable with respect to age and sex, and the clinical and biological parameters (sedimentation rate and fibrin) would allow us to discern the difference, if any, between the two populations. Plasma fibronectin assay has no diagnostic or discriminating value on a large scale. PMID- 2210969 TI - Diabetic ulcer healing preparations from the skin of the Arabian Gulf catfish (Arius bilineatus Val.): a novel and effective treatment. AB - A novel and simple treatment for healing of infected diabetic foot ulcers in uncontrolled diabetes mellitus patients was devised. The preparations which involve aqueous extracts from the skin of the Arabian Gulf catfish are enriched with different fractions from the same source and with catfish lipids. Eight patients with non-healing foot ulcers and two with wet gangrene were treated. It was found that the ulcers were completely healed. The gangrenic feet noticeably improved in 48 h. The treatment resulted in natural debridation of the necrotic tissues. The ulcer site was invaded by angiogenesis and granulation tissues. Sensation returned to the otherwise neuropathic extremity. The rate of growth of new tissues was proportional to the amount of healing material applied, and its effect ceased shortly after the interruption of the treatment. No. atrophy of the skin lesions was noted and no side-effects were detected. PMID- 2210970 TI - New ligands for human C-reactive protein: calcium-dependent binding with epsilon aminocaproic acid-agarose and calcium-independent binding with omega-aminohexyl agarose. AB - Human C-reactive protein (CRP) is an acute phase protein which increases in concentration in response to inflammation. CRP has been known to bind with phosphorylcholine in a calcium-dependent manner. In this study, CRP is found to bind to affinity chromatography of negatively-charged epsilon-aminocaproic acid agarose when calcium ions are present, and to the affinity chromatography of positively-charged omega-aminohexyl-agarose if a normal ionic strength of NaCl exists but calcium ion is not present. PMID- 2210971 TI - Reactive oxygen species and hyaluronate in serum and synovial fluid in arthritis. AB - Oxygen-derived free radicals (ODFR) depolymerized synovial-fluid (SF) hyaluronic acid (HA) when hypoxanthine/xanthine oxidase (HX/XAO) was used as the radical generator. The molecular-weight distribution of ODFR-induced SF HA degradation products was determined using high performance liquid chromatography (HPLC) with TSK 5000 PW or TSK 6000 PW size-exclusion columns and simultaneously using 125I labelled hyaluronate-binding protein (125I-HABP) assay. The exposure of SF HA to hydroxyl-radical flux resulted in the formation of a degradation product having a molecular weight of 13.5 X 10(3) daltons, from which no further degradation was achieved. If the iron chelator desferrioxamine and hydroxyl-radical scavenger mannitol were present in the reaction mixture, the HA peak decreased by 30-50%, as a result of reaction with superoxide radical and hydrogen peroxide. These results show that superoxide radical and hydroxyl radical may have different modes of action on SF HA. The molecular-weight distribution of serum HA from patients with rheumatoid arthritis varied in different individuals and ranged between 275 X 10(3) and 650 X 10(3). PMID- 2210972 TI - Comparison of three dosage regimens of ciprofloxacin in urinary tract infections. AB - Fifty-four patients with complicated UTI were administered ciprofloxacin in doses of 500 mg (30 subjects) and 250 mg (24 subjects) at 12-hour intervals. While a positive effect was noted in 96-100% upon termination of therapy, the effect was still present 3 weeks later in 90% of the high-dose, but only in 71% of the low dose group. In 23 patients with uncomplicated UTI, a positive effect of the three day therapy with 100 mg of ciprofloxacin at 12-hour intervals was observed in 91% of subjects. Intolerance to the agent was found in one case only. Development of resistance to ciprofloxacin was not observed. PMID- 2210973 TI - Nephrectomy in unilateral chronic pyelonephritis. A long-term follow-up study. AB - In order to study the effectiveness of unilateral nephrectomy as a treatment for chronic unilateral pyelonephritis, 15 consecutive patients who had undergone this operation were followed up. The patients had been operated on 8.9 years (mean) earlier. All of the 15 patients had had recurrent urinary tract infections prior to the operation, 11 of them had had pyelonephritis for between 1 and 19 (mean 6.7) years. One patient only had had a verified episode of urinary tract infection during the follow-up period. All 15 patients were hypertensive prior to the operation. At the time of follow-up, 7 patients were normotensive without drugs, and 2 were normotensive with a reduced dosage of antihypertensives. The mean systolic blood pressure went down from 180 to 150 mm Hg, and the mean diastolic pressure from 109 to 88 mm Hg. This operation can thus be recommended in selected cases of unilateral chronic pyelonephritis with hypertension. PMID- 2210974 TI - Can a relationship reflect the risk of calcium oxalate urolithiasis? AB - Different mathematical expressions have been proposed in the literature with the aim to reflect the risk of calcium oxalate urolithiasis. Such expressions, as well as a number of new relationships proposed by us, have been evaluated in 76 patients and 34 normal subjects. Stone-formers were divided into two groups: patients with normal calcium and oxalate excretion and patients with hypercalciuria and/or hyperoxaluria. The results obtained were comparatively evaluated. Several formulae gave some acceptable results, but none of them were excellent. This can be explained by the fact that these discrimination indexes more or less reflect supersaturation and/or inhibition deficit, but none of them reflect promoting factors such as heterogeneous nucleation and/or aggregation capacity. PMID- 2210975 TI - Early onset of stone diseases and primary hyperoxaluria. AB - A case of primary hyperoxaluria is presented. In a product of consanguinous marriage recurrent stone formation, nephrocalcinosis and increased urinary oxalate excretion revealed the diagnosis of hyperoxaluria. Diagnosis and treatment of primary hyperoxaluria are briefly reviewed and the importance of elevated urinary oxalate level in diagnosis is emphasized. PMID- 2210976 TI - Multi-organ involvement in urothelial malignancies. AB - The present study covers 1213 patients with urothelial tumours, of whom 113 have been affected by multi-organ malignancies. The disease was found to spread mostly in direction of the urine flow. Bladder was the most frequently affected organ. The incidence of pelvic cancer in China is higher than in Western countries. PMID- 2210977 TI - Androgen receptors in transitional cell carcinoma. AB - Androgen receptors were measured in transitional cell carcinoma tissues obtained from 13 patients with bladder tumours and 3 patients with ureteric tumours. Scatchard analysis of binding of mibolerone, a synthetic androgen, was used for receptor measurement. None of the patients were receptor positive. This study suggests that human male hormones do not play any direct role in the malignant transformation of human transitional cell epithelium. PMID- 2210978 TI - Failed partial nephrectomy: local recurrence vs. multicentric disease. AB - Candidates for partial nephrectomy for renal cell carcinoma include those with (1) bilateral synchronous lesions, (2) tumour in a solitary kidney and (3) renal mass and borderline renal function. Present imaging techniques aid in the identification of appropriate candidates for partial nephrectomy and in the preoperative assessment for technical feasibility of the operation. Studies have shown that the postoperative local recurrence rate ranges from 9 to 13%. We submit a case report in which a 65-year-old male with a history of colon carcinoma four years earlier was found to have a 3 cm left lower pole lesion on his follow-up abdominal CT scan. Upon intended partial nephrectomy, a small synchronous upper pole mass was noticed as well as numerous cortical lesions despite extensive preoperative imaging to the contrary. It is our feeling that finer imaging techniques including thinner CT cuts, additional imaging planes and continued use of renal ultrasound will aid in the identification of ipsilateral, synchronous lesions and draw further distinction between local recurrence and multicentric disease. PMID- 2210979 TI - Traumatic rupture of the ureter. AB - A case of rupture of the ureter from blunt trauma is described. The clinical signs of trauma to the trunk of the patient were very discrete. The police report made it possible to reconstruct the events of the accident and to propose a mechanism of the injury. PMID- 2210980 TI - Oxybutynin hydrochloride in the management of detrusor instability. AB - The results of an investigation dealing with the therapy of instability of the detrusor using oxybutynin hydrochloride are presented. Out of an unselected group of patients 21 were enrolled in the trial. After therapy 19 patients showed significant improvement of subjective symptoms and objective urodynamic parameters. Twenty patients reported on tolerable side effects. PMID- 2210981 TI - Complete androgen blockade as primary treatment for advanced metastatic cancer of the prostate. AB - The results of a series of non-randomized studies suggest that complete androgen blockade, i.e. medical or surgical castration in association with an antiandrogen, is superior to castration alone as regard survival potential. This report presents 11 untreated patients (Stage T2-4, Nx, M1), who were treated with complete androgen blockade, orchiectomy and a pure antiandrogen (Flutamide 250 mg three times a day). The rate of subjective response was 100% and the median time to progression was 12 months. The objective response rate was 82% and the rates of partial remission at one and two years were 45% and 18%, respectively. The survival rates after one and two years were 91% and 53%, respectively, a result which is consistent with that of other studies on the survival of patients with metastatic cancer of the prostate treated with either diethylstilboestrol, orchiectomy or LH-releasing hormones. The results of this study do not support the hypothesis that androgen blockade improves the survival of patients with advanced metastatic cancer of the prostate. PMID- 2210982 TI - Efficacy of prophylactic antimicrobial regimens in preventing infectious complications after transrectal biopsy of the prostate. AB - In a prospective study on 81 patients undergoing transrectal needle biopsy of the prostate, the efficacy of prophylaxis in preventing postbiopsy infectious complications was determined. The patients were divided randomly into four groups, and a comparison of the rate of postbiopsy complications in each group was made. In 11 and 17% of the patients in Group A (n = 18) who received povidone iodine enema alone, bacteriuria and bacteraemia, respectively, occurred. When parenteral piperacillin alone in Group B (n = 22) was administered, the rates of the same complications were 9 and 14%, respectively, while both rates were as low as 4% in Group C (n = 25) when piperacillin in combination with povidone-iodine enema was given. On the other hand, in 31 and 37.5% of the patients in Group D (n = 16), who served as controls, bacteriuria and bacteraemia developed. The study has thus shown that parenteral piperacillin in combination with povidone-iodine enema significantly reduces the incidence of infectious complications associated with transrectal prostatic biopsy. PMID- 2210983 TI - Intralesional corticosteroid injections in combination with internal urethrotomy in the treatment of urethral strictures. AB - In the treatment of 38 patients with urethral stricture, 21 received intralesional corticosteroid injections, combined in 17 cases with internal urethrotomy. The aetiology of the lesion is discussed, together with a review of the pertaining literature, and the results of the treatment are evaluated. PMID- 2210984 TI - Transitional cell carcinoma of distal female urethra. AB - A rare case of carcinoma of female urethra from transitional cell origin is reported. The occurrence of primary transitional cell carcinoma in the urethra is being discussed, with review of the literature. PMID- 2210985 TI - Volume change of the prostate and seminal vesicles in male hypogonadism after androgen replacement therapy. AB - Before and after androgen replacement therapy prostatic and seminovesicular volume was estimated by means of transrectal ultrasonography in 13 hypogonadal men. Volume of the prostate (p less than 0.001) and seminal vesicles (p less than 0.01) significantly increased after treatment with testosterone enanthate. However, the plasma level of testosterone remained abnormally low. These results indicate that volume determination of the prostate and seminal vesicles by means of transrectal ultrasonography is suitable for evaluating the adequacy of androgen replacement therapy in male hypogonadism. PMID- 2210986 TI - Water immersion induced alterations of plasma vasopressin levels and activity of the renin-angiotensin-aldosterone system in noninflammatory acute renal failure and end-stage renal failure. AB - Water immersion (WI) induced alterations of plasma renin activity (PRA), plasma aldosterone (Aldo), vasopressin (AVP), sodium and potassium concentrations and plasma volume (PV) were examined in 12 patients with noninflammatory acute renal failure (NARF) in the anuric/oliguric phase, in 20 patients with chronic renal failure (CRF) and in 15 healthy subjects. In all examined groups a significant increase of PV and decrease of PRA, plasma Aldo, AVP after WI were observed. Significantly more marked decreases of PRA were observed in patients with NARF than in those with CRF and in healthy subjects. In patients with NARF the increase of PV was significantly greater than in CRF and in healthy subjects. In patients with NARF a significantly more marked decrease of plasma sodium concentration was also noted after WI than in subjects with CRF and in normals. Only in healthy subjects was a significant negative correlation noted between the WI increase of PV and decrease of plasma AVP level. In healthy subjects, significantly positive correlations were noted between WI induced decrease of PRA and Aldo and between PRA and plasma AVP, respectively. Such correlations were absent in uraemic patients. IN CONCLUSION: (1) patients with CRF and NARF show similar, but quantitatively different responses of PRA, Aldo and AVP secretion to WI as compared with normals; (2) patients with NARF and CRF are characterized by an inappropriate volumetric and osmotic regulation of AVP secretion; (3) in uraemic patients the physiological relationship between the renin-angiotensin system and AVP secretion seems to be dissociated. PMID- 2210987 TI - Comparison of captopril and enalapril in the treatment of hypertension in patients with non-insulin dependent diabetes mellitus and nephropathy. AB - Eighteen patients with non-insulin dependent diabetes mellitus (NIDDM), hypertension and nephropathy were randomized to receive captopril or enalapril for 6 months. Two patients with serum creatinine of greater than 400 mumol/l had to be excluded from the study because of rapidly deteriorating renal function after starting treatment. Of the remaining patients, 7 received captopril and 9 received enalapril. Blood pressure control was achieved in about 50% of patients with either drug alone. Serum creatinine and creatinine clearance were unchanged in both groups but there was a greater tendency for the former to increase in patients with higher pretreatment values. Proteinuria was reduced at 1 month only in the enalapril group which also showed a significant elevation of serum potassium after treatment. Captopril and enalapril have only a modest antihypertensive action in patients with NIDDM and nephropathy. Their use in patients with renal insufficiency must be balanced against the risk of further aggravating the deterioration of renal function. PMID- 2210988 TI - Ciprofloxacin iontophoresis for aminoglycoside-resistant pseudomonal keratitis. AB - Studies using ciprofloxacin for the therapy of experimental aminoglycoside resistant keratitis caused by Pseudomonas aeruginosa were conducted using transcorneal iontophoresis as the drug-delivery system. Corneas infected with P. aeruginosa ATCC 27853/pMG6 were treated 22 hours postinfection with ciprofloxacin delivered by iontophoresis (0.8 mA X 10 min), mock iontophoresis (eyecup with no current), or frequently applied topical drops. Iontophoresis of 10 mg/ml or 25 mg/ml of ciprofloxacin significantly reduced the number of viable bacteria per cornea by more than 5 log units compared with untreated controls (P less than 0.0001). Five hours after the initiation of treatment, mock iontophoresis (10 mg/ml or 25 mg/ml) or 11 applications of topical ciproflaxicin drops (7.5 mg/ml) decreased the viable bacteria relative to the untreated controls by 5 log units (P less than 0.0001). One treatment with an eyecup was as effective as 11 treatments with topical drops (P greater than 0.75). One hour after treatment with iontophoresis or mock iontophoresis of 10 mg/ml of ciprofloxacin, aqueous humor concentrations were 83.75 +/- 8.85 micrograms/ml and 24.87 +/- 4.0 micrograms/ml (mean +/- standard error of the mean), respectively. One hour after the last of five applications of 7.5 mg/ml of ciprofloxacin (every 15 min for 1 hr) the aqueous humor concentration was 4.2 +/- 1.14 micrograms/ml. These results show the value of ciprofloxacin in treating aminoglycoside-resistant infections caused by P. aeruginosa and suggest that ciprofloxacin can be efficiently delivered by iontophoresis. PMID- 2210989 TI - Generation of complement-derived anaphylatoxins in normal human donor corneas. AB - Complement-derived anaphylatoxins (C3a, C4a, and C5a) are potent, stable mediators of acute inflammation. Because human corneas contain functional complement, the authors subjected normal human donor corneas to various forms of immunologic or chemical injury to determine if the complement system could be activated and anaphylatoxins generated. The experimental cornea of each donor pair was injected with lipopolysaccharide (LPS) or immune complexes or injured by application of acid or alkali. The remaining cornea of each donor pair served as a control. After incubation of corneas in tissue culture media for 6 hours and elution in phosphate-buffered saline for 24 hours, C3a, C4a, and C5a were measured in corneal eluates by radioimmunoassay. Compared with control corneas, C3a levels were significantly increased in corneas injected with LPS or immune complexes and in corneas injured with acid or alkali. C4a levels were significantly elevated in corneas injected with immune complexes and in corneas injured with acid or alkali but not in corneas injected with LPS. C5a levels were detectable only in corneas injured with acid or alkali. These results suggest that immunologic reactions in the human cornea may activate the classic or alternative complement pathways and generate anaphylatoxins. Additionally, chemical injuries with acid or alkali generate anaphylatoxins in the cornea. Anaphylatoxins may participate in the acute inflammatory response of the human cornea to chemical or immunologic injury. PMID- 2210990 TI - Intracameral injection of allogeneic lymphocytes enhances corneal graft survival. AB - Failure of corneal grafts is thought to involve the development and activation of specifically sensitized T-cells. One method which might be used to circumvent the development of such cells is the phenomenon of anterior chamber-associated immune deviation (ACAID). Injection of antigen into the anterior chamber of the eye leads to an immune response characterized by normal antibody response coupled with depressed T-cell reactivity especially as measured by delayed-type hypersensitivity. To determine if this phenomenon could be used to alter the course of graft failure, potential recipients (Lewis rats) were injected intracamerally (IC) with allogeneic lymphoid cells (Wistar-Furth). Orthotopic, full-thickness, penetrating keratoplasty was done 0-30 days later, and the recipients were observed for at least 60 days. Approximately 75% of Wistar-Furth corneal grafts placed on uninjected Lewis rats failed as evidenced by continued opacity, edema, and infiltration of mononuclear cells into the grafts. The IC injection of Wistar-Furth lymphocytes decreased this failure rate to 25% and 50% when grafting was done 14 and 7 days after injection, respectively. Grafts of cornea from a third strain onto IC injected animals failed at an intermediate rate which demonstrated some immunologic protection. The results of these studies indicate that IC injection of allogeneic lymphocytes results in prolonged acceptance of corneal grafts syngeneic with the injected lymphocytes. PMID- 2210991 TI - Kinetics of corneal epithelium turnover in vivo. Studies of lovastatin. AB - The authors developed a direct chemical approach for estimating the rate of turnover of the corneal epithelium in vivo. The method was used to examine the effects of lovastatin, a potent inhibitor of cholesterol biosynthesis, on proliferation and turnover of the epithelium. Corneal DNA was labeled by pulse injection (IP) of the rat with 3H-thymidine, and 3H-labeled DNA was recovered from peripheral and central corneas over the next 15 days. Only the epithelium became labeled, and the loss of label by cell desquamation began 3 days after injection. The loss of 3H-DNA from the cornea (peripheral plus central region) followed first-order kinetics. The half-life of the disappearance was about 3 days. The peripheral cornea became more highly labeled than the central cornea and began to lose 3H-DNA before the central cornea. These observations support the possibility of a higher mitotic rate in the peripheral region and the centripetal movement of a population of peripheral epithelial cells in the normal cornea. The half-lives of the disappearance of 3H-DNA from peripheral and central corneas measured between days 5 and 15 postinjection were identical, both at 3 days. Complete turnover of the corneal epithelium would, therefore, require about 2 weeks (4-5 half-lives). Treatment of the rat with lovastatin had no obvious effects upon the proliferation or turnover of the corneal epithelium. Although lovastatin inhibited corneal 3-hydroxy-3-methylglutaryl coenzyme A reductase, the key regulatory enzyme of cholesterol synthesis, the cornea compensated by induction of this enzyme so that there was no net inhibition of cholesterol synthesis in the cornea. PMID- 2210992 TI - Inhibition of corneal inflammation by an acylated superoxide dismutase derivative. AB - Superoxide radicals and their metabolite(s) have been postulated to play an important role in the pathogenesis of inflammation. Hence, superoxide dismutase (SOD) has been used to reduce tissue injury caused by reactive oxygens. However, protection of the cornea and other ocular tissues from oxygen toxicity could not be achieved by administering SOD presumably due to its unfavorable in vivo behavior. To scavenge superoxide radicals on the outer surface of corneal epithelial cells, the authors synthesized an acylated SOD derivative (AC-SOD) by linking capric acid. When instilled into rabbit eyes, a significant amount of AC SOD remained bound to the corneal surface for a fairly long time. Intracorneal injection of lipopolysaccharide (LPS) triggered infiltration of polymorphonuclear leukocytes (PMNs) to the cornea and induced severe keratitis. Topical administration of AC-SOD to the LPS-treated cornea markedly inhibited the infiltration of PMNs and suppressed the occurrence of keratitis. Under identical conditions, topically administered SOD was rapidly removed by tears and, hence, did not inhibit LPS-induced keratitis. When the number of PMNs in the systemic circulation was reduced by intravenous administration of hydroxyurea, LPS-induced keratitis was inhibited markedly. These results indicate that superoxide radicals and circulating PMNs might play a critical role in LPS-induced keratitis. PMID- 2210993 TI - Biochemical analyses of proteoglycans in rabbit corneal scars. AB - Macromolecules from normal rabbit cornea and cornea containing a 2-mm diameter button of scar tissue were biosynthetically labeled with 35S-sulfate and 3H glucosamine in vivo and in organ culture. Labeled macromolecules, including proteoglycans (PGs) extracted from the normal cornea, scar tissue, and corneal tissue adjacent to the scar with guanidine hydrochloride were chromatographed on DEAE-Sepharose CL-6B columns and eluted with increasing concentrations of NaCl. The elution pattern of corneal macromolecules synthesized in vitro was remarkably similar to that in vivo. In another experiment, corneas having 2-, 4-, and 8-week old scars were labeled in organ culture and also extracted. Scars synthesized PGs with lower sulfation than those of adjacent corneal tissue. Although PG synthesis in scar decreased with wound age, the synthesis in adjacent cornea remained the same. In a third experiment, PGs extracted from pools of unlabeled 2- and 4-week old scars, adjacent corneal tissue, and normal corneas were chromatographed on ion-exchange columns and analyzed chemically. The quantity of PGs in scar and adjacent cornea increased with healing time. The ratios of keratan sulfate PG to dermatan sulfate PG in normal cornea, scar, and adjacent cornea was 2.3, 0.6, and 1.5, respectively. The PGs from adjacent corneal tissue had a higher charge density than those from scar. The predominant adjacent-cornea dermatan sulfate PG had a higher charge density than that in normal cornea. The authors conclude that cornea adjacent to the healing wound synthesized PGs measurably different fro those in scar and normal cornea. PMID- 2210994 TI - Characterization of a 66-kilodalton surface glycoprotein of the human corneal endothelium. AB - The pellet recovered after centrifugation (5000 X g) of human corneal endothelial homogenates was used as the source of membranes in these studies. A 66-kilodalton (kD) protein was identified as the most abundant protein in the particulate pellet by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The de novo synthesis of the 66-kD protein by endothelial cells was observed during culturing of human corneas in the presence of 35S-methionine. The 66-kD protein was found to be a plasma membrane protein based on several of its properties, ie, its solubility in CHCl3:CH3OH, its labeling as surface glycoprotein, and during exposure to a photoaffinity hydrophobic probe: 1-azido-4-125I-iodobenzene. Furthermore this protein could be released from the particulate pellet after treatment with phosphatidylinositol-specific phospholipase C, suggesting its anchorage via a phosphatidylinositol glycan linkage in the plasma membrane. Such anchorage of this protein was further confirmed by its labeling during culture of corneas in the presence of 3H-myoinositol. The glycoprotein nature of the 66-kD protein was evident from its labeling during surface glycoprotein labeling of endothelial cells, staining with periodic acid-Schiff stain, and binding to peanut agglutinin (PNA), and lotus agglutinin (LTA) on SDS-acrylamide gels. The 66-kD protein of endothelial particulate pellets recovered from corneas of donors of different ages showed an age-related increase in binding to PNA and LTA. This suggested an increased glycosylation of the 66-kD protein with aging. A polyclonal anti-66-kD protein antibody was used as a probe to determine the presence of this protein in the rabbit and bovine corneal endothelia by the Western-blot analysis. The 66-kD protein was detected in both rabbit and bovine endothelia, but an additional immunoreactive species of 17 kD was also observed which may be a processed product of the 66-kD protein. PMID- 2210995 TI - Loss of stromal glycosaminoglycans during corneal edema. AB - This study tried to determine if glycosaminoglycans (GAGs) are released from the rabbit stroma during corneal edema. The GAGs of rabbit corneas were labeled in situ using anterior-chamber injections of 35S-sulfate and 3H-glucosamine. Labeled corneal pairs were excised and the endothelium perfused in vitro in the specular microscope. Edema was induced in one cornea by perfusion with a calcium-free balanced salt solution; the control cornea was perfused with glutathione bicarbonate Ringer's (GBR). Corneal thickness was measured every 15 minutes during the 3-hour perfusion period, and perfusate fractions were collected from each cornea and analyzed for the presence of GAGs. Edematous corneas swelled from 438 +/- 14.8 microns to 688 +/- 10.6 microns compared with control corneas (427 +/- 4.7 microns to 454 +/- 7.2 microns). Total 3H-glucosamine (4.00 +/- 0.68%) and 35S-sulfate (10.36 +/- 0.92%) released from the edematous corneas during perfusion exceeded that lost by control corneas (1.92 +/- 0.18% for 3H glucosamine; 3.23 +/- 0.52% for 35S-sulfate). Enzymatic digestion studies showed the presence of keratan sulfate in the edematous perfusates. The results suggest that increased loss of radiolabeled components from edematous corneas represent a loss of stromal GAGs and possibly GAG fragments. Therefore, corneal edema involves loss of GAGs and water uptake. PMID- 2210996 TI - Corneal edema recovery dynamics in the rabbit. A useful model? AB - Open-eye and closed-eye recovery from contact lens-induced corneal edema was measured on the right eyes of 10 New Zealand White rabbits using ultrasound pachometry. Edema was produced by either 2 hours of eye closure (Patch Test) or 2 hours wearing of a thick hydrogel contact lens over the closed eye (Lens Test). The measured corneal edema recovery data were analyzed by both linear-regression analysis and nonlinear-regression analysis based on a previously published exponential open-eye edema recovery model. Linear-regression analysis revealed that the initial rabbit open-eye edema recovery rate of 36.3 +/- 11.9 (standard deviation) micron/hr was not significantly different (P greater than 0.25) from the initial young human open-eye edema recovery rate of 35.6 +/- 3.4 micron/hr. Similarly, the initial rabbit closed-eye edema recovery rate of 14.3 +/- 5.4 micron/hr was found to be not significantly different (P greater than 0.25) from the initial young human closed-eye edema recovery rate of 15.0 +/- 2.2 microns/hr. Corneal edema recovery indices derived using nonlinear-regression analysis also had a strong similarity between rabbit and human corneal edema recovery rates. For example, the calculated percent recovery per hour (PRPH) for rabbit open-eye corneal edema recovery of 41.4 +/- 11.3%/hr agreed well with the reported human open-eye PRPH of 34.2-58.9%/hr. The rabbit closed-eye PRPH of 25.6 +/- 10.7%/hr was also found to lie between the calculated human closed-eye PRPH values of 19.9-30.2%/hr.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210997 TI - A cryodamage model for studying corneal nerve regeneration. AB - This study used a transcorneal freezing technique to produce a 2-mm circular, central wound in the rabbit cornea for investigating corneal nerve regeneration. All the corneal cells, nerves, and associated Schwann cells were dead inside the wound, but the extracellular matrix components remained intact. The destroyed epithelium and endothelium were replaced in 1 and 5-7 days, respectively. The necrotic keratocytes and stromal and subepithelial nerves were removed completely in 1-3 days by invading macrophage-like cells. The wounded stroma was repopulated centripetally by migrating keratocytes between days 1-5. Two types of nerve growth were identified in the stroma. The first type was novel sprouting of straight, long neurites between days 2-21, initially from the undamaged, periwound nerves and later from regenerated stromal nerves inside the wound. These small-caliber neurites proliferated in a random and disorderly pattern both inside and outside the wound and sometimes terminated on stationary, stellate keratocytes. The second type was genuine regrowth of stromal and subepithelial nerves in a centripetal direction between days 3-7. Schwann cells appeared on the newly formed nerves starting on day 4 or 5. A near-normal pattern and size of the nerves were established in the wound as early as day 10. In the epithelium, transient, wound-oriented neurites (days 1-3), single nerves, and semileashes (days 4-10) appeared. A near-normal leash pattern was restored between days 10-21 only at the wound periphery. Thus, in this model, the major groundwork of nerve regeneration occurred between days 3-10, simultaneously, at all three levels of nerve organization. These data suggest that nerve-Schwann cell interaction contributes to the restoration of stromal and subepithelial nerves, whereas a reparative epithelium deficient in trophic activity may account for the incomplete regrowth of epithelial nerves. The cryodamage model offers an efficient and multifaceted system for the experimental study of corneal nerve regeneration. PMID- 2210998 TI - Accuracy of the microkeratome keratectomies in pig eyes. AB - Keratokyphosis is a procedure of lamellar refractive corneal surgery in which corneal tissue does not have to be frozen. Corneal lamellae of 30 pig eyes were separated with either the Berlin microkeratome developed for keratokyphosis or the Barraquer microkeratome. The layer thickness was measured within the optical area at 25 measuring points 0.2-mm apart using the Universal Measuring Microscope. Corneal lamellae separated parallel to the surface by means of the Berlin microkeratome showed layer-thickness differences of 0.008 +/- 0.028 mm in the optical zone between the beginning and end of the incision. When using a convex applanation surface in the microkeratome with an optical zone of 5 mm and a vertex of 0.22, 0.2, and 0.15 mm, the vertex of the central part of the optical zone in the corneal disc attained a value of 0.114 +/- 0.018 mm instead of 0.114 mm (100%), 0.075 +/- 0.015 mm instead of 0.105 mm (72%), and 0.076 +/- 0.014 mm instead of 0.080 mm (84%) (mean +/- standard deviation [SD]). When using a concave applanation surface with the same vertex, it attained 0.076 +/- 0.020 mm (67%), 0.075 +/- 0.019 mm (72%), and 0.067 +/- 0.027 mm (84%). The measured vertex of the corneal lamellae was shifted up to 0.8 +/- 0.5 mm in the feed direction of the microkeratome, probably due to the frictional forces acting on the blade during the cutting process. After separation of the lamellae, the cut surface of the eye was measured planimetrically.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2210999 TI - Cell-mediated immunity against human retinal extract, S-antigen, and interphotoreceptor retinoid binding protein in onchocercal chorioretinopathy. AB - Autoimmune mechanisms are thought to be involved in the pathogenesis of onchocercal chorioretinopathy. Cell-mediated immune responses to human retinal S antigen, interphotoreceptor retinoid binding protein (IRBP), and crude retinal extract were investigated in patients with onchocerciasis from Sierra Leone, West Africa using a two-step migration-inhibition factor assay. Patients were subdivided into three groups: (1) without ocular involvement (n = 10), (2) with ocular onchocerciasis limited to the anterior segment (n = 19), and (3) with onchocercal chorioretinopathy (n = 21). A group of endemic controls (n = 25) from Sierra Leone were also studied. The cellular immune response to concanavalin A (Con A) was measured to assess the general capacity of lymphocytes to respond to a mitogen. Four of 50 (8%) patients with onchocerciasis and four of 25 (16%) endemic controls reacted with at least one retinal antigen. From the patients with onchocercal chorioretinopathy two of 21 (10%) showed a positive cellular response. The general mitogen response tested with Con A was positive in all these individuals. A role for an antiretinal autoimmune mechanism in the pathogenesis of onchocercal chorioretinopathy, as studied with human S-antigen, IRBP, or crude retinal extract, could not be shown because the cellular response to these antigens did not differ in patients with or without onchocercal chorioretinopathy or in endemic controls. PMID- 2211000 TI - Retinoblastoma. The relationship of proliferating cells to blood vessels. AB - In 150 retinoblastomas the authors found a uniform thickness of the cuff of viable retinoblastoma cells that surrounds blood vessels. The mean thickness was 98.7 microns with a standard deviation of 11.9 microns. The cross-sectional area of the cuff was negatively correlated with the mitotic activity in the cuff and positively correlated with the diameter of the central vessel. The mitotic activity in the cuff of cells was inversely related to the distance from the central blood vessel. When the cuff was divided into three concentric rings, the inner ring contained a mean of 6.2 mitotic figures, the middle ring contained a mean of 2.9 mitotic figures, and the outer ring contained a mean of 0.6 mitotic figures. This pattern of growth is similar to that observed in other rapidly growing neoplasms in humans and experimental animals. In these tumors this pattern results from reduction in oxygen tension with increased distance from the central blood vessel. PMID- 2211001 TI - Retinal blood flow during hyperglycemia. A laser Doppler velocimetry study. AB - The effect of different rates of glucose infusion on the retinal circulation was studied in Gottingen breed minipigs. Seven minipigs were made hyperglycemic rapidly with an intravenous bolus injection of 50% dextrose, after which a slow dextrose infusion maintained hyperglycemia for 60 minutes. Seven minipigs were more gradually made hyperglycemic over 60 minutes with a slow intravenous infusion of 50% dextrose, and a further seven had a control infusion of urea of equal volume and osmolality over 60 minutes. Retinal blood flow (RBF) was determined from the maximum (centerline) velocity of the blood (Vmax) (determined by bidirectional laser doppler velocimetry) and the vessel diameter (D) (determined from monochromatic fundus photographs). Measurements were made in a single temporal retinal vein of each animal at baseline, during, and after each of the infusions. Plasma glucose rose from 6.1 +/- 0.5-25.3 +/- 1.5 mM (mean +/- standard error) during the bolus infusion and from 6.4 +/- 0.7-22.0 +/- 0.7 mM during the slow infusion. The bolus and the slow glucose infusions both produced large increases in RBF (63% and 62%, respectively) which were mainly attributable to increases in Vmax. The urea infusion had no significant effect on RBF, Vmax, or D. The ocular perfusion pressure rose slowly and was significantly elevated after 60 minutes of slow glucose infusion but not after the urea infusion. PMID- 2211002 TI - Retinal adhesiveness is weakened by enzymatic modification of the interphotoreceptor matrix in vivo. AB - The role of interphotoreceptor matrix (IPM) constituents in mediating adhesion between the retina and retinal pigment epithelium (RPE) was investigated by injecting specific enzymes into rabbit eyes either intravitreally or subretinally. Retinal adhesiveness was measured by peeling the retina from the pigment epithelium 1-3 days later and observing the amount of adherent pigment. Effects of enzymes on the IPM were monitored by observation of peanut agglutinin (PNA) binding to cone matrix sheaths; retinal and RPE toxicity was excluded by electroretinography and histology. Three enzymes that degrade glycosaminoglycans or saccharides known to be constituents of the IPM (chondroitinase ABC, neuraminidase, and testicular hyaluronidase) both weakened adhesion and altered PNA binding, although the effects on the cone matrix sheaths were different for each enzyme. An enzyme specific for hyaluronic acid (Streptomyces-derived hyaluronidase), which has not been identified as a major IPM constituent, had no effect on either adhesion or PNA binding. The authors conclude that IPM associated glycoconjugates participate in retinal adhesion, although their precise composition, interaction with IPM components, and relationship to other mechanisms of adhesion remain to be determined. PMID- 2211003 TI - Analysis and fractionation of silicone and fluorosilicone oils for intraocular use. AB - Silicone oil (SiO) and fluorosilicone oil (FSiO) are useful in difficult cases of retinal detachment surgery. Unidentified low-molecular-weight components (LMWC) and residual catalysts in SiO and FSiO have been implicated in the adverse reactions of the oils in the eye. The authors analyzed LMWC of SiO and FSiO using a gas chromatograph (GC) equipped with a 6-ft x 2-mm column packed with 3% SP 2250 and a flame-ionization detector. By commercially available standards and a homologous series plot, MD3M to MD23M (linear LMWC) and D4 to D30 (cyclic LMWC) were positively identified in commercial-grade 1000-centistokes (cs) SiO. Commercial-grade 12,500-cs SiO contained GC-detectable LMWC (up to MD28M and D30) at higher concentrations than commercial-grade 1000 cs SiO, although the weight percent of acetone-extractable LMWC (including those larger than MD28M and D30) was less in the former than in the latter. The GC-detectable LMWC in most medical grade SiO were less than those in commercial-grade SiO. Tetramethylammonium siloxanolate (a residual catalyst) and tributylphosphine oxide (a heat decomposition product of a polymerization catalyst) were tentatively identified in commercial- and medical-grade 12,500-cs SiO, respectively. Commercial-grade 1000- and 10,000-cs FSiO also contained LMWC, including F3 and/or F4 (cyclic LMWC). To eliminate LMWC from the oils, the authors developed a solvent fractionation method using acetone for SiO and hexane for FSiO. After continuous solvent extraction of SiO for 2 weeks and FSiO for 3 weeks, all measurable LMWC were eliminated from the oils. PMID- 2211004 TI - The A-wave of the human electroretinogram and rod receptor function. AB - The amplitude of the leading edge of the a-wave of the human electroretinogram (ERG) was compared with predictions from a computational model of the light induced responses of rod mammalian receptors. According to this model, a linear process describes the amplitude and time course of the response to relatively low flash intensities and at brief times after the onset of the flash. At higher flash intensities, a nonlinear process, described by the Naka-Rushton function or a saturating exponential, is involved. The primary focus here is on intensity response data recorded with a clinical ganzfeld apparatus. The leading edge of the rod a-wave recorded from normal observers and patients with congenital stationary night blindness (CSNB) was described by a linear process for flash intensities up to the maximum available flash intensity, 2.0 log scot td-sec. This finding is consistent with the model of the rod's response. It suggests, however, that when ERGs are recorded with clinical systems limited to 2.0 log scot td-sec, these data cannot be used to distinguish between changes in the parameters (eg, semisaturation intensity versus maximum response) of the human rod receptors. Responses to flash intensities up to 3.4 log scot td-sec were recorded using a custom, high-intensity ganzfeld system. Both the linear and nonlinear components of the model were needed to fit the ERGs recorded with this system. This suggests that changes in different receptor parameters can be distinguished with higher intensity flashes. PMID- 2211005 TI - Development of grating acuity in infants with regressed stage 3 retinopathy of prematurity. AB - The acuity card procedure was used to measure grating acuity in 17 infants with regressed Stage 3 retinopathy of prematurity (ROP) who had no lasting anatomic changes in the retina or optic nerve. Results were compared with those of 28 healthy preterm infants and 28 infants matched by birth weight and gestational age who did not have Stage 3 ROP. Infants in the ROP group showed delayed grating acuity development until 2 years of age. This difference among groups was significant at the 3-5- and 10-12-month test ages but not at the 0-1-, 8-9-, and 16-18-month test ages. Post hoc analyses indicated that the delay in acuity development shown by the ROP group was due to the poor acuity scores of the infants in that group who had central nervous system abnormalities of periventricular leukomalacia or severe (Grade III or IV) intraventricular hemorrhage. When the data of these infants were removed from the analysis, the ROP group showed acuity development similar to that of both the healthy preterm group and the group of infants with matched birth weights and gestational ages who did not have Stage 3 ROP. PMID- 2211006 TI - Entoptic visualization of the retinal vasculature near fixation. AB - The authors review (1) the range of techniques used to study the retinal vasculature near the fovea, (2) describe the need and rationale for noninvasive in vivo monitoring of the retinal vasculature, (3) present theoretic and practical considerations which show that entoptic visualization of the smallest capillaries near the fovea is optimized by a small short-wavelength source (1 mm or less) rotating at 3.5 hertz in a circular path (radius 2 mm) imaged in the plane of the eye's entrance pupil, and (4) discuss the feasibility of using these techniques as a research and clinical tool. PMID- 2211007 TI - Retinal fixation point location in the foveal avascular zone. AB - The site of normal fixation is often assumed to be centered in the foveal avascular zone (FAZ). This assumed anatomic relationship is used during photocoagulation therapy as an objective guide to avoid damaging critical retinal structures on or near fixation. With laser therapy being directed closer and closer to the center of the FAZ, the accuracy with which the center of the FAZ locates the retinal point of fixation becomes an important therapeutic issue. Using an optimized technique for visualizing the retinal vasculature entoptically, the authors determined the location of the retinal point of fixation with respect to the foveal area vasculature in 26 eyes of 14 healthy subjects. In 23 eyes (12 subjects), a traditional FAZ was observed, the other three eyes (two subjects) had capillaries near or crossing the center of fixation. Of the 23 eyes with a traditional FAZ, 20 had centers of fixation located eccentric to the center but in the FAZ, (average deviation from the center of the FAZ, 66.5 +/- 49.5 microns) with the direction of deviation from the FAZ center appearing random. Consequently, when following protocols that advocate photocoagulation treatment with spot centers closer to the FAZ center than 300 microns, the center of the FAZ is a poor locator of a subject's retinal point of fixation. When using the FAZ as a reference, the resulting uncertainty in the location of the subject's retinal point of fixation increases the probability of significant damage to the actual point of fixation by up to 20%. PMID- 2211008 TI - Analysis of lymphocytic infiltration in uveal melanoma. AB - Among 27 uveal melanomas, five were found to contain tumor infiltrating lymphocytes (TILs). Four had high levels of lymphocytes, and the fifth had comparatively low levels but adequate numbers for comprehensive analysis. The TILs were analyzed by flow cytometry to determine the relative proportions of lymphocyte subsets and markers of lymphocyte activation. The results show the predominance of T-suppressor/cytotoxic lymphocytes and insignificant levels of B cells present in the infiltrate. The T-suppressor/cytotoxic cells were generally activated to a higher degree than the T-helper cells when assayed for levels of the histocompatibility antigen, HLA-DR. T-helper cells expressed more interleukin (IL-2) receptor (Tac) than T-suppressor/cytotoxic cells. PMID- 2211009 TI - Analysis of aqueous humor immunoglobulin G in uveitis by enzyme-linked immunosorbent assay, isoelectric focusing, and immunoblotting. AB - Immunoglobulin G (IgG) in aqueous humor from patients with various uveitis syndromes was analyzed using a number of immunologic techniques. Sixty-five percent of patients with Fuchs' heterochromic cyclitis (FHC), 70% of patients with other forms of uveitis, and 44% of controls showed local synthesis of IgG, as demonstrated by an elevated IgG:albumin relative concentration ratio. Using an enzyme-linked immunosorbent assay to measure the concentration of IgG subclasses 1-4, a relative excess of IgG1 was found in the aqueous compared with the serum in FHC. Isoelectric focusing and immunoblotting studies revealed oligoclonal IgG bands in the aqueous of 13 of 23 (57%) patients with FHC, most being of the IgG1 subclass. Oligoclonal bands were not found in 18 patients with other types of uveitis or 13 patients undergoing surgery for senile cataract. These findings indicate intraocular production of IgG of restricted specificity in FHC, providing further evidence for local immune dysfunction in this condition. As yet the antigenic stimulus for this oligoclonal B-cell response has not been identified. PMID- 2211010 TI - Effects of mithramycin, mitomycin, daunorubicin, and bleomycin on human subconjunctival fibroblast attachment and proliferation. AB - Scar formation and fibrosis are the most common causes of ultimate glaucoma filtration surgery failure. The authors used Coulter counter, hexosaminidase, and 3H-thymidine assays to evaluate the effects of mithramycin, mitomycin, daunorubicin, and bleomycin on human subconjunctival fibroblast growth in tissue culture. Fifty percent inhibitory doses (ID50) for each drug on different days of incubation with fibroblasts were calculated with these three assays. Among these four drugs only daunorubicin exerted a significant effect on cellular attachment, showing cytotoxicity at 4 x 10(-6) M. However, all drugs had antiproliferative effects. Daunorubicin was the most potent drug in the concentration range studied. Mithramycin had a narrow therapeutic range in tissue culture. Cellular antiproliferative responses to mitomycin and bleomycin were more gradual. These drugs have potential applications in the prevention of glaucoma filtration surgery failure. PMID- 2211011 TI - Transscleral microwave cyclodestruction. AB - A 4.6-gigahertz (GHz) microwave applicator was used to ablate the ciliary body in rabbit eyes. High-frequency electromagnetic radiation provides a favorable dose distribution to induce local heating of the ciliary body. For treatment, a 3-mm diameter disc-shaped applicator was placed on the conjunctiva and over the ciliary body. Conjunctival temperatures were monitored during treatment with a built-in thermocouple thermometer located at the center of the disc-shaped antenna. This allowed direct measurement (dosimetry) of the conjunctival temperature during treatment. Using this microwave-based heat-delivery system, doses in a range of 60 degrees for 30 or 60 seconds appeared to cause ciliary body damage with relative sparing of the conjunctiva and sclera. PMID- 2211012 TI - Human trabecular meshwork phagocytosis. Observations in an organ culture system. AB - Perfusion organ culture of the trabecular meshwork was used to study the phagocytic ability of human trabecular cells. Cultured eyes were challenged with blood, latex microspheres, or zymosan particles for periods of 1 hour to 7 days. Trabecular cells were capable of ingesting all three types of particles. The presence of a foreign particle did not necessarily induce a phagocytic response, however, as free particles were seen in the intertrabecular spaces and Schlemm's canal. In contrast to studies in animals which indicate trabecular cell migration from the eye may play a role in the removal of foreign debris, limited human trabecular cell migration was observed. The effect of the culture process on trabecular cell phagocytosis was also studied, using adult cats. One eye received a phagocytic challenge in vivo with the fellow eye later receiving the phagocytic challenge in vitro. Phagocytosis was demonstrated in each eye, although more cells were involved with phagocytosis in vivo. The additional cells involved in vivo may have been recruited by an accompanying inflammation. Organ culture of human trabecular meshwork may be useful in the study of trabecular cell phagocytosis, and it allows separation of the effects of inflammation from the potential effects of phagocytosis itself. PMID- 2211013 TI - Increase in lens gangliosides due to aging and cataract progression in human senile cataract. AB - Gangliosides were isolated from human senile cataractous lenses by solvent extraction, DEAE-Sephadex column chromatography, and thin-layer chromatography. The content and composition of gangliosides were examined in individual lens tissues. Three predominant gangliosides, GM3, GM1, and GD1a, were tentatively identified in comparison with authentic brain gangliosides, and several unidentified gangliosides were also recognized. The increase in ganglioside content per mg of protein content in cataractous lenses was found to be influenced by two physiologic parameters: aging and cataract progression. The mature cataractous lenses showed a higher ganglioside level on a protein basis than the immature lenses compared with the same age group. On the basis of statistical analysis, an age-dependent increase in ganglioside concentration was recognized in both mature and immature lens groups. The relative increase in slow moving polysialogangliosides on thin-layer chromatography seemed to be caused by the maturation of cataract. The sugar composition of one of the polysialogangliosides was found to be glucose, galactose, and sialic acid in the molar ratio of 2:1:4; this suggests the presence of a unique ganglioside species in human cataractous lens. PMID- 2211014 TI - Photodamage to calf lenses in vitro by excimer laser radiation at 308, 337, and 350 nm. AB - Calf lenses in vitro were irradiated using an excimer laser at wavelengths of 308, 337, and 350 nm for times ranging from 10 minutes to 5 hours. The laser power was 2.0 watts (W) at 308 nm, 0.2 W at 337 nm, and 2.0 W at 350 nm. During irradiations, the visible light transmission (632.8 nm) of the lenses was measured and found to be decreased markedly with 308- or 337-nm irradiation. No change in visible light transmission was observed with irradiation at 350 nm. Irradiated lenses were also compared with dark control lenses by photographic record. Lenses exposed to 308-nm ultraviolet (UV) radiation for 10-30 minutes showed significant yellow-brown pigmentation and colorless opacification compared with dark controls. Lenses exposed to 337-nm UV light showed primarily colorless opacity with little pigment production. Lenses exposed to 350-nm radiation for up to 1 hour were visibly indistinguishable from dark controls. After photolysis, the lenses were separated into water-soluble and insoluble fractions and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Compared with dark controls, UV-exposed lenses (308 or 337 nm) showed loss of 20-30-kilodalton (kD) material and production of higher molecular weight material at 40-60 kD and greater than 100 kD. There was no evidence of such changes after 350-nm exposure. The data gave the following order for the degree of photodamage: 308 nm approximately 5 x 337 nm greater than 20 x 350 nm. An action spectrum for lens damage is presented. PMID- 2211015 TI - The role of the iris in accommodation of rhesus monkeys. AB - After unilateral total iridectomy, maximum accommodation inducible by corneal iontophoresis of carbachol in rhesus monkeys was approximately 40% less in the iridectomized than in the contralateral untouched eyes, irrespective of age. Ultrasonographically measured anterior chamber shallowing and lens thickening were also less in the iridectomized eyes. Neither submaximal accommodation induced by intramuscular pilocarpine infusion nor maximum accommodation inducible by midbrain stimulation differed in iridectomized and intact eyes. The authors hypothesize that at maximum cholinomimetic drug-induced contraction, the iris sphincter muscle pulls the ciliary body farther forward and inward than does maximum ciliary muscle contraction alone, allowing additional rounding of the lens and, consequently, additional accommodative power. PMID- 2211016 TI - Effect of calcium ion concentration on the permeability of the corneal endothelium. AB - The effect of free Ca2+ ion concentration on the integrity of the barrier function of the corneal endothelium was studied using the endothelial permeability to carboxyfluorescein (Pac) as a quantitative index according to the method of Araie. Paired rabbit corneas were isolated and mounted in a chamber. To serve as a control, one eye of each pair was perfused with a glucose-glutathione bicarbonate solution at a Ca2+ concentration of 1.1 mEq, the other with a solution at various Ca2+ concentrations ranging from 0.23-1.1 mEq. The Pac ratio of a solution with a Ca2+ concentration of 0.38 mEq or higher to the control solution was close to unity, and the Pac ratio of a solution with a Ca2+ concentration of 0.33 mEq or lower to the control solution was significantly greater than unity. In a separate experiment, it was found that only slight swelling was seen when a solution with a Ca2+ concentration of 0.23 mEq or higher was used; significant swelling was seen with a solution of a Ca2+ concentration of 0.17 mEq or lower. The lowest free Ca2+ concentration needed for maintaining the barrier function of the corneal endothelium, 0.38 mEq, was found to be higher than that needed for maintaining the corneal thickness, 0.23 mEq. PMID- 2211017 TI - Oxygen and developmental retinal capillary remodeling in the kitten. AB - During the recovery period after a high oxygen injury in the kitten, chronic hypoxia adversely affects the resulting retinopathy, but increasing oxygen breathing to 28% improves it. To test the effects of chronic hypoxia without an antecedent hyperoxic injury in the kitten, the animals were raised in 13% or 21% (room air) oxygen and their retinas examined at 3, 7, 14, or 21 days. They were also studied after 14 days of exposure to 30% or 40% oxygen to compare the graded effects of elevated oxygen to that of hypoxia on the development of the retinal capillary bed. Chronic hypoxia alone did not affect somatic growth or cause retinopathy. An inverse relationship was found between the rate of retinal vascularization and ambient oxygen. As inspired oxygen rose from 13%-40%, the proportion of the retina vascularized at 14 days fell from 76 +/- 12%-18 +/- 8% (mean +/- standard deviation, P less than 0.01). All 14-day animals had similar capillary density at the advancing edge of their retinal vasculature (mean diameter of the capillary meshwork = 71 +/- 12 microns) despite the impairment of forward progress observed in elevated oxygen. However, the width of the periarteriolar capillary-free zone increased from 65 +/- 10 microns in 13% oxygen breathing animals to 104 +/- 5 microns in 40% oxygen-breathing animals (P less than 0.001). The animals raised in hypoxic conditions had more mature-appearing retinal vasculature at 21 days than did controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2211018 TI - Interglial cell gap junctions increase in urethane-induced photoreceptor degeneration in rats. AB - Gap junctions are found between astrocytes in the inner retina of normal rats, but they are rare between Muller cells or between astrocytes and Muller cells in the inner retina. After photoreceptor degeneration induced by urethane treatment of newborn animals, morphologic alterations of glial cells occur in the inner retina. The Muller cells withdraw from the inner limiting membrane, and the astrocytes hypertrophy and occupy the vitread surface of the inner limiting membrane. The frequency and size of the gap junctions between astrocytes increases with time in rats with urethane-induced photoreceptor degeneration, to a greater extent than expected from elaboration of additional astrocyte plasma membrane. The gap junction-profile length per glial cell membrane-contact length is 2.8 +/- 1.1 microns/1000 microns of membrane in 8-week-old normal animals; it increases to 18.9 +/- 9.4 microns/1000 microns of membrane at 56 weeks of age in urethane-treated animals. The average size of the gap junction-profile length doubles during this same period. To the authors' knowledge this is the first study demonstrating pathologic changes in gap junctions in central nervous system tissue. The authors speculate that this up-regulation of gap junctions occurs in response to an altered extracellular ionic composition in an attempt to increase the lateral spatial buffering of K+ by these cells. The relative location of glial cells in retina can determine, in part, the vulnerability of the retina to edema. PMID- 2211019 TI - Acuity card assessment of visual function in the cryotherapy for retinopathy of prematurity trial. AB - The primary outcome measure of the effectiveness of cryotherapy in the original design of the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) was the anatomic status of the retina, as documented by fundus photography 3 months and 12 months after infants had received treatment. The authors describe the addition of a measurement of visual function, the Acuity Card procedure, to the CRYO-ROP study. After training, four visual-acuity testers attempted to measure monocular grating acuity in all randomized infants and approximately one fourth of the natural-history infants in the study, tested at 1 year postcryotherapy or 1 year postterm. In 95% of infants on whom testing was attempted, monocular acuity values from each eye were obtained. Interobserver test-retest results on 25 eyes of 13 randomized infants agreed to within one octave or better in all but one of the eyes. The high testability rate and good interobserver agreement suggest that the Acuity Card procedure has been a successful method of assessing visual function in the CRYO-ROP study. PMID- 2211020 TI - Modulation of growth in retina-derived cells by extracellular matrices. AB - Intravitreal membranes from patients with proliferative vitreoretinopathy (PVR) consist partly of retinal glial (RG) and retinal pigment epithelial (RPE) cells surrounded by varying amounts of extracellular matrix (ECM). The contribution of the ECM to the growth of PVR membranes is unknown. This study was undertaken to determine if proliferation in cultured RPE and RG cells is affected by different substrates, including some ECM materials which have been identified in PVR membranes. Substrates tested included type I collagen, basement membrane Matrigel, and poly-D-lysine, as well as uncharacterized cell type-specific matrices deposited by cultured RPE and RG cells. Proliferation was quantified by 3H-thymidine incorporation and radioautography 24 hours after plating and by cell counts after 14 days in the presence of serum. Relative to uncoated culture plastic, growth of RPE cells was inhibited by Matrigel, enhanced by poly-D lysine, and unaffected by type I collagen. In contrast, growth in RG cells was inhibited by type I collagen and unaffected by the other substrates. Analysis of the timing of DNA synthesis after plating suggested that the substrates which affected RPE growth did so by altering the fraction of cycling cells rather than the cell cycle time. For the cell-derived matrices, heterotypic matrix (matrix produced by the other retinal cell type) enhanced the growth of both RPE and RG. The results suggest that the ECM may modify the growth of cells contributing to PVR membranes. Of note is that the cell-derived matrices reciprocally stimulated growth of RG and RPE cells, cell types which may interact in PVR membranes. PMID- 2211022 TI - 31P magnetic resonance spectroscopy of animal uveal melanoma. AB - Scleral surface coils were used to obtain in vivo magnetic resonance spectra (MRS) of Greene melanoma implanted in the rabbit uvea. Well-localized tumor spectra (4.7 Tesla) with good signal-to-noise ratios (S/N) were obtained from the tumor with a "single-pulse" sequence in less than 1 hour. Tumor localization was confirmed with one-dimensional spectroscopic imaging studies. Serial 31P spectra were obtained during tumor growth and after both optimal and suboptimal hyperthermia. Early 31P MRS change is correlated with tumor treatment response and preceded histologic evidence of cell destruction. Twenty-four to 48 hours after successful treatment, the inorganic phosphate/nucleoside triphosphate (NTP), and phosphomonoester/NTP ratios were significantly increased from 1.2 +/- 0.1 to 1.7 +/- 0.1 and 1.3 +/- 0.1 to 1.8 +/- 0.2, respectively. In contrast, untreated or ineffectively treated tumors showed little change. Interpretation of 31P MRS data in this animal uveal melanoma model after the first week was complicated by decreased S/N, increased contamination from contiguous tissues, ingrowth of fibroblasts, macrophages, and intratumor hemorrhage. PMID- 2211021 TI - Intraocular radiation blocking. AB - Iodine-based liquid radiographic contrast agents were placed in normal and tumor bearing (Greene strain) rabbit eyes to evaluate their ability to block iodine-125 radiation. This experiment required the procedures of tumor implantation, vitrectomy, air-fluid exchange, and 125I plaque and thermoluminescent dosimetry (TLD) chip implantation. The authors quantified the amount of radiation attenuation provided by intraocularly placed contrast agents with in vivo dosimetry. After intraocular insertion of a blocking agent or sham blocker (saline) insertion, episcleral 125I plaques were placed across the eye from episcleral TLD dosimeters. This showed that radiation attenuation occurred after blocker insertion compared with the saline controls. Then computed tomographic imaging techniques were used to describe the relatively rapid transit time of the aqueous-based iohexol compared with the slow transit time of the oil-like iophendylate. Lastly, seven nontumor-bearing eyes were primarily examined for blocking agent-related ocular toxicity. Although it was noted that iophendylate induced intraocular inflammation and retinal degeneration, all iohexol-treated eyes were similar to the control eyes at 7 and 31 days of follow-up. Although our study suggests that intraocular radiopaque materials can be used to shield normal ocular structures during 125I plaque irradiation, a mechanism to keep these materials from exiting the eye must be devised before clinical application. PMID- 2211023 TI - Microwave hyperthermia for choroidal melanoma in rabbits. AB - Radiation has provided excellent local control rates in choroidal melanoma, but significant impairment in visual acuity has occurred in 30-60% of patients due in part to the development of radiation vasculopathy in the fovea and optic disc. Hyperthermia has been shown to have a synergistic effect when added to radiation therapy in human malignancies. The use of hyperthermia in ocular melanoma may allow a reduction in the total radiation dose necessary to achieve local control. A 2450-MHz microwave plaque applicator with integral surface cooling was used to deliver hyperthermia treatments to rabbit eyes containing choroidal melanomas. Extensive thermal mapping was done in acute eyes. In 18 survival animals, a single 23-G needle thermocouple probe with three sensors was inserted into the tumor. Target temperatures of 41.0-46.0 degrees C were maintained for 1 hour. All tumor-bearing eyes were followed for 1 month after treatment, or until tumor growth was noted, with serial ultrasound measurements and visual examinations. A 92% response rate was obtained in tumors treated at temperatures greater than 43.0 degrees C for 1 hour with no significant toxicity. Heat alone has significant tumoricidal properties in this animal model. PMID- 2211024 TI - The mechanism of accelerated corneal epithelial healing by human epidermal growth factor. AB - The effect of biosynthetic human epidermal growth factor (hEGF) was investigated on a 10-mm diameter corneal epithelial defect model in rabbits. Topical application of over 10 micrograms/ml of hEGF five times a day significantly enhanced the epithelial healing rate, in a dose-dependent manner. The maximum healing rate was observed in eyes treated with 20 micrograms/ml of hEGF (1.59 +/- 0.26 mm2/h), whereas application of less than 5 micrograms/ml of hEGF did not increase the rate of epithelial regeneration compared statistically with control vehicles (1.03 +/- 0.24 mm2/h). S-phase analysis indicated that hEGF treatment induced a high rate of epithelial replication, particularly near the limbal region, during 12 to approximately 24 hours after wounding, followed by massive cell replication from 1 mm behind the leading edge through the limbus during 24 48 hours. The change in number and distribution of S-phase cells thereafter did not essentially differ between hEGF-treated and control groups. In concordance with the S-phase analysis, there was a statistically significant increase in the DNA content in regenerating epithelium at 48 and 72 hours in the hEGF-treated group. These findings indicate that hEGF-induced acceleration of large corneal epithelial wound healing is associated with about twofold cell replication in the regenerating epithelium during 24 to approximately 48 hours after wounding. It is concluded that cell proliferation induced by hEGF, particularly that in limbal and peripheral corneal epithelial cells, may play an important role in accelerating epithelial healing. PMID- 2211025 TI - Single potassium channels in corneal epithelium. AB - The basal cell layers of the rabbit and human corneal epithelia contain a frequently occurring ionic channel whose unitary currents can be recorded in cell attached or excised membrane patches by use of a patch voltage clamp. The channel is highly conductive (165 pS in 150 mM K+ salts) and is very selective for K+ over Na+ (PK/PNa greater than 40:1). Its open probability is increased by the application of suction to the recording pipette although its gating is less sensitive to suction than that of many other "stretch-activated" channels reported. The current through the channel is a saturating function of the K+ concentration in the bathing solutions with half saturation occurring at 480 mM and a single-channel current at saturation (imax) of 31 pA. In the absence of applied suction, the open probability is extremely variable from patch to patch and shows little voltage dependence over the physiologic voltage range. The channel also gates frequently to several subconductance levels. It is blocked by external Cs+ and Ba+2 in the 0.1-10 mM range but not by most other K+ channel blockers. It is also partially blocked by Ca+2 at both its internal and external surfaces. Because of its novel properties (stretch activation and large conductance), it can be used to measure the input resistance and total capacitance of single dissociated cells. PMID- 2211026 TI - Changes in corneal innervation during postnatal development in normal rats and in rats treated at birth with capsaicin. AB - This study was undertaken to learn more about the keratitis that follows the neonatal administration of capsaicin to rats. In the first part of the study the density and pattern of corneal innervation were followed throughout postnatal development in litters of control rats and in rats that received capsaicin as neonates. In rats treated with capsaicin, the density of corneal innervation was lower than that of control rats until 28 days of age. Thereafter nerve fiber sprouting was observed within the corneas of capsaicin-treated rats. By 56 days of age the capsaicin-treated rats had a denser corneal innervation than did control rats. In the second part of the study the incidence and severity of the corneal trophic changes induced by capsaicin were studied in litters of rats treated with chronic tarsorrhaphy and in litters raised in the dark. Neither of these manipulations altered the incidence or severity of keratitis. These observations demonstrate that sprouting of the remaining corneal axons is related temporally to the previously observed decrease in keratitis. Furthermore the more severe keratitis observed in early postnatal life does not appear to be related to physical injury of the cornea. PMID- 2211027 TI - In vitro pharmacologic separation of corneal endothelial migration and spreading responses. AB - Repair of corneal endothelial wounds involves two forms of cell translocation: (1) "migration," in which individual cells at the wound edge break contacts with neighboring cells and move as individuals into the wound defect, and (2) "spreading," in which cells within the confluent monolayer adjacent to the wound move as a group into the wound area. The authors combined morphometric analysis of Giemsa-stained cultures, phase-contrast video microscopy, and Rh-phalloidin staining of actin filaments to study the effects of epidermal growth factor (EGF) and indomethacin on the migratory and spreading responses to wounding using an in vitro wound-closure model which mimics the amitotic state and general behavior of human corneal endothelium. They found that EGF stimulated the migration of individual cells from the wound edge, induced cellular elongation, and promoted a diffuse distribution of actin filaments. Indomethacin promoted spreading of the confluent monolayer into the wound defect, induced enlargement and flattening of cells, and promoted the formation of long, thick actin stress fibers. These results provide evidence that the migration and spreading responses of corneal endothelial cells to wounding can be pharmacologically separated. The findings suggest that migration of individual cells during wound repair may result from an endogenous form of EGF-like stimulation and that the elongated shape associated with this form of translocation results, at least in part, from an EGF-like alteration in actin-filament organization. Spreading of the confluent monolayer to cover the wound defect may result from a decrease in cyclic adenosine monophosphate induced by a transient reduction in prostaglandin E2 synthesis. This form of translocation may result, in part, from enlargement and flattening of corneal endothelial cells secondary to an enhancement of actin stress-fiber formation. PMID- 2211029 TI - Changes in aqueous outflow after in vitro neodymium: yttrium aluminum garnet laser cyclophotocoagulation. AB - To examine the possible role of transscleral outflow routes, enucleated human and porcine eyes underwent noncontact neodymium:yttrium aluminum garnet (Nd:YAG) laser cyclophotocoagulation 3 mm posterior to the limbus. Pars plana lesions were verified histologically. The eyes were perfused with saline solution at 50 mm Hg perfusion pressure, placing the tip of the needle into the hyaloid orbicular space. The outflow facility was 0.072 microliter/min/mm Hg in paired controls and 0.105 microliter/min/mm Hg in human lasered eyes, a difference of 31%. In porcine eyes the difference was 43%. Since concepts of aqueous production, impaired circulation, and inflammation do not apply to enucleated eyes, the increase may be related to pars plana transscleral flow facilitated by disruption of the neuroepithelial barrier. PMID- 2211028 TI - Improved ocular: systemic absorption ratio of timolol by viscous vehicle and phenylephrine. AB - Increasing the ocular absorption of timolol relative to its systemic absorption is important clinically because ophthalmic timolol may cause serious respiratory, cardiac, and central nervous system side effects. The authors evaluated the effects of phenylephrine coadministration and solution viscosity on the aqueous humor:plasma and iris ciliary body:plasma ratios of peak timolol concentrations after ocular application. Timolol eye drops (5 mg/ml, 25 microliters) were administered to the eyes of pigmented rabbits. Coadministered phenylephrine (0.8 8.2 mg/ml) decreased the systemic peak concentrations of timolol significantly. Since ocular absorption of timolol was not affected by phenylephrine, the ocular:systemic concentration ratios were improved four- to fivefold. Phenylephrine slows down the systemic absorption of timolol by constricting the conjunctival and nasal capillaries. The ratios of the aqueous humor:plasma and iris ciliary body:plasma peak concentration of timolol were improved three- to ninefold in the presence of sodium carboxymethylcellulose compared with nonviscous eye drops. The improved ocular penetration is probably due to the longer corneal contact, and the decreased rate of systemic absorption may be caused by the slower spreading of the solution on the nasal mucosa. Compared with timolol eye drops, the ratio of the eye:plasma peak timolol concentrations was improved tenfold by using viscous eye drops with phenylephrine. Systemic concentrations of ophthalmic timolol and possibly related side effects can be decreased when timolol is instilled in a viscous vehicle with a low phenylephrine concentration. PMID- 2211030 TI - In situ localization of cytoskeletal elements in the human trabecular meshwork and cornea. AB - The authors compared cytoskeletal elements of the in situ human trabecular meshwork cell with in situ human corneal cells using indirect immunofluorescence staining for tubulin and intermediate filaments (vimentin, cytokeratin, and desmin) and NBD-phallacidin staining for f-actin using both fixed frozen and unfixed frozen sections from postmortem eyes. Both f-actin and tubulin were found throughout the cell body of trabecular-meshwork cells, keratocytes, corneal endothelium, and corneal epithelium. The f-actin staining pattern was concentrated at the cell periphery of these four cell types. Vimentin stain was intensely localized in focal areas of the trabecular-meshwork cell, keratocytes, and throughout the corneal endothelium. A general anticytokeratin antibody was intensely localized in corneal epithelium and endothelium. However, PKK-1 anticytokeratin antibody was seen only in superficial layers of corneal epithelium and not in corneal endothelium. The 4.62 anticytokeratin antibody was not observed in either corneal epithelium or endothelium. None of these three cytokeratin antibodies were seen in trabecular-meshwork cells or keratocytes. Desmin stain was not noted in any of these cell types. In general, cytoskeletal staining of unfixed frozen sections showed a similar staining pattern for f-actin and tubulin but a more uniform and intense staining pattern for vimentin and cytokeratin compared with fixed frozen material. The authors conclude that these cytoskeletal stains can differentiate human trabecular-meshwork cells from cells of the cornea in situ. PMID- 2211031 TI - The effect of 5-fluorouracil and cytarabine on human fibroblasts from Tenon's capsule. AB - The in vitro cellular inhibitory effects of two pyrimidine antimetabolites, 5 fluorouracil (5-FU) and cytarabine (ara-C), on the attachment and proliferation of human Tenon's capsule fibroblasts after 1, 2, 3, 5, 7, and 10 days of growth were measured with a Coulter counter, a colorimetric method using the endogenous enzyme hexosaminidase, and 3H-thymidine uptake. Neither 5-FU nor ara-C affected cell attachment. The 50% inhibitory dose (ID50) for 5-FU, as measured by the Coulter counter and hexosaminidase assay, was 0.2 and 0.4 micrograms/ml, respectively, at day 5 and decreased to 0.01 and 0.10 micrograms/ml, respectively, on later days. The ID50 for ara-C as measured by the Coulter counter and hexosaminidase assay was 0.01 and 0.1 micrograms/ml at day 3 and remained constant over time. Much lower ID50s were measured by thymidine uptake for both drugs. These findings may indicate that 5-FU has a delayed effect on cellular proliferation due to conversion into more active metabolites. The ara-C has a direct and constant inhibitory effect on cellular proliferation and is ten times more potent than 5-FU as an antiproliferative drug. Thus ara-C may have clinical utility in preventing failure of glaucoma filtering surgery. PMID- 2211032 TI - Electrophysiological and psychophysical flicker sensitivity in patients with primary open-angle glaucoma and ocular hypertension. AB - Temporal sensitivity was assessed in patients with primary open-angle glaucoma (POAG) and ocular hypertension (OHT). Three measures of flicker sensitivity were obtained: psychophysical modulation thresholds, visual-evoked potentials (VEPs), and focal electroretinograms (FERGs). We found elevated psychophysical thresholds at higher temporal frequencies (30-50 Hz) in patients with POAG, relative to thresholds for age-matched controls. The OHT patients had elevated psychophysical thresholds only at 50 Hz. On the other hand, VEP amplitudes in POAG patients were reduced at all temporal frequencies, with the magnitude of the loss increasing with temporal frequency. The OHT patients, however, showed no reductions in VEP amplitude at any temporal frequency. Finally, POAG patients' FERG amplitudes were reduced at 30-50 Hz; whereas FERG amplitudes in the OHT patients were normal at all temporal frequencies. These results indicate that OHT patients can exhibit psychophysical threshold losses at high temporal frequencies which are not observed in the suprathreshold electrophysiological amplitude measures. On the other hand, patients with POAG show both psychophysical and VEP losses across a range of temporal frequencies. In addition, the decreases in FERG amplitudes in POAG patients suggest changes in the functioning of the outer retina in this disease. PMID- 2211033 TI - Color perimetry for assessment of primary open-angle glaucoma. AB - The authors report the development of a color perimetry procedure which compares sensitivity of the short-wavelength color-vision mechanism in the peripheral visual field for normal eyes, eyes with ocular hypertension, and eyes with primary open-angle glaucoma. To isolate the short-wavelength cone mechanism, they modified an automatic projection perimeter to blue-on-yellow color perimetry and used a monochromatic 440-nm stimulus and a broad-band bright yellow background. The three groups of subjects were matched for age and lens density. Refraction, pupil size, acuity, and medication were controlled. Under these conditions, most glaucomatous eyes showed reduced sensitivities more than two standard deviations below normal. Normal control eyes were significantly different from eyes with ocular hypertension only in the superior nasal field (P less than 0.05), but normal eyes differed from eyes with primary open-angle glaucoma in all areas of the field (P less than 0.01). PMID- 2211034 TI - Early morphogenesis of persistent hyperplastic tunica vasculosa lentis and primary vitreous. A transmission electron microscopic study. AB - This report provides transmission electron microscopic observations on the early pathogenesis of persistent hyperplastic tunica vasculosa lentis/persistent hyperplastic primary vitreous (PHTVL/PHPV) in affected canine fetuses at days 28 44 postcoitum. The retrolental tissue by which this anomaly is characterized consists of loosely arranged fibroblasts in a randomly oriented meshwork of collagenous fibrils. Some of these cells contain melanosomes at day 44. In one day-44 eye, cells of neuroectodermal origin (Muller cells; fibrous astrocytes) were observed. From day 37 onward, the posterior subcapsular part of the lens contains rounded, increased intercellular spaces, resembling vacuoles, which deform the shape of the lens fibers. The posterior lens capsule develops normally until day 30. From day 35 onward the capsule has an amorphous ultrastructure, as opposed to the clearly laminated ultrastructure in reference eyes at day 35. In addition, the capsule's thickness increases until day 35, and, instead of growing thicker, decreases thereafter. Based on these results, it is hypothesized that a primary metabolic disorder in the lens fibers, subsequently leading to the formation of an abnormal posterior lens capsule, constitutes the primary defect in the sequence of events leading to PHTVL/PHPV. PMID- 2211035 TI - The dyschromatopsia of optic neuritis is determined in part by the foveal/perifoveal distribution of visual field damage. AB - Most hypotheses of acquired dyschromatopsia invoke the mechanism of selective damage to specific components of the afferent visual system to explain the predominance of red-green and blue-yellow hue-discrimination defects found in neural and retinal disorders, respectively. However, this pattern of hue discrimination disturbance in ocular disease may vary. There are frequent exceptions which are inadequately explained by existing hypotheses. In an effort to explain the pattern and pathogenesis of acquired dyschromatopsias better, the authors examined patients with nonproliferative diabetic retinopathy (DR) and late-stage retrobulbar neuritis (RBN) using age-corrected Farnsworth-Munsell 100 hue testing and threshold static perimetry. As expected, most DR eyes showed some degree of relative blue-yellow dyschromatopsia (89%) with few showing a greater weighting towards red-green dyschromatopsia (11%). However, an approximately equal number of RBN eyes had a relative blue-yellow (48%) versus red-green dyschromatopsia (52%). For RBN, the authors found a strong association between the spatial distribution of field defect and the type of relative hue discrimination disturbance. Eyes with greater field depression at the fovea relative to the perifovea showed a relative preponderance of red-green dyschromatopsia (68%) as opposed to blue-yellow dyschromatopsia (32%), whereas eyes with greater relative perifoveal impairment showed a relative preponderance of blue-yellow dyschromatopsia (100%). This relationship between the relative spatial distribution of visual field damage and the relative hue-discrimination deficit in RBN was statistically significant (P = 0.002). Such an association was not found for DR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2211036 TI - Conjunctival transdifferentiation is due to the incomplete removal of limbal basal epithelium. AB - Previous studies have shown that using n-heptanol to create a total corneal epithelial defect beyond the limbus results in two different healing patterns with an unpredictable incidence. Between 14-68% of these wounded rabbit corneas (n = 287, combining various reports) showed extensive vascularization and conjunctivalization, whereas the remaining were not vascularized and had conjunctival transdifferentiation with a cornea-like epithelium. To investigate the role of the limbal epithelium in these two healing patterns, the authors treated rabbit eyes for various durations with n-heptanol and additional scraping. Histology showed that treatment for up to 120 seconds removed both the corneal and conjunctival epithelia but left the limbal basal cells intact. To prove viability, they cultured the treated limbal explants on collagen gel. After 14 days of culture, increased stratification of the limbal epithelium and an epithelial outgrowth onto the corneal stroma was observed. The latter was proven to be of corneal origin (positive to AE-5 but negative to AM-3 monoclonal antibody staining). The authors then surgically removed the entire limbal zone including 2 mm of peripheral cornea and 3 mm of adjacent conjunctiva in addition to n-heptanol debridement of the entire corneal epithelium in 54 rabbit eyes and observed a high incidence (96%) of corneal vascularization and conjunctivalization of the resultant epithelial phenotype (positive to AM-3, but negative to AE-5 monoclonal antibody staining). These results support the hypothesis that corneal epithelial stem cells are located in the limbus and indicate that an incomplete removal of the basal limbal epithelium by n-heptanol leads to unvascularized corneas with conjunctival transdifferentiation. Conversely, complete removal of such cells results in corneal vascularization and conjunctivalization. PMID- 2211037 TI - Long-term effect of acetazolamide in a patient with retinitis pigmentosa. AB - The authors studied the therapeutic effect of acetazolamide on a patient with autosomal dominant retinitis pigmentosa complicated by retinal edema. In addition to reduction of macular edema and some improvement of central vision, they found an unexpected progressive increase in extrafoveal retinal sensitivity with prolonged medication. It is proposed that the therapeutic effect is mediated by alteration of retinal pigment epithelial function and that disturbed polarity is restored to a more normal state. PMID- 2211038 TI - Blood velocity in the ophthalmic artery in normal subjects and patients with endophthalmitis. AB - Some ocular diseases lead to temporary changes in the ocular blood circulation. This study was undertaken to evaluate changes in the blood-flow velocity of the ophthalmic artery in patients with endophthalmitis. With pulsed Doppler sonography the blood velocity of the ophthalmic artery was measured in 50 normal subjects and in ten patients with bacterial endophthalmitis. In normal subjects blood velocity decreased with increasing age, and the average systolic/diastolic blood velocity in cm/sec were 38.8 +/- 6.3/11.6 +/- 4.7 in the 18-50-year-old age group and 28.3 +/- 4.6/6.7 +/- 3.3 in the 51-88-year-old age group. Endophthalmitis produced increased systolic/diastolic blood velocity in the ophthalmic artery in the affected eyes in cm/sec (99.7 +/- 15.5/26.6 +/- 10.5 in the 16-50-year-old age group; 60.4 +/- 8.8/16.6 +/- 4.8 in the 51-83-year-old age group). Some patients showed similar changes in the unaffected fellow eyes. The noted elevation of the blood velocity in unaffected eyes may be due to the bilaterally projected parasympathetic fibers of the oculomotor nerve. PMID- 2211039 TI - Human presaccadic spike potentials. Of central or peripheral origin? AB - Electroencephalographic (EEG) activity associated with voluntary and spontaneous saccades were analyzed in 12 normal subjects to determine the influence of volition upon the presaccadic spike potentials (SPs). In addition, two different electrode configurations, of a temporal and a parietal derivation, and two different filter bandwidths were simultaneously analyzed to clarify issues regarding the structure, function, and origin of SPs. An off-line averaging of the pre- and postsaccadic EEG epochs showed distinct spike potentials associated with spontaneous saccades in both the temporal and the parietal locations. Subsequent statistical analyses indicated that the amplitude of the SPs associated with spontaneous saccades was not significantly different from the respective amplitude of SPs preceding voluntary saccades. Independent effects of filter bandwidth and electrode derivation are suggestive of a complex late presaccadic EEG activity. PMID- 2211040 TI - Effect of additional cations on the twitching reaction to intracarotid, nonionic contrast media in rabbits. AB - Previous investigations in this laboratory have confirmed the observation of facial muscle twitching during intracarotid injections of nonionic contrast media (CM) in rabbits. The reaction appears to be a locally mediated effect. To further investigate this reaction, cortical electroencephalogram (EEG) and facial electromyogram (EMG) recordings were made from rabbits receiving selective internal carotid artery (ICA) and external carotid artery (ECA) injections of CM. The effects of iopromide and iohexol were compared with and without the addition of sodium (Na) and calcium (Ca) ions at different concentrations. External carotid injections of iopromide also were performed in some animals paralyzed with D-tubocurarine to exclude the possibility that the reaction is due to an effect on peripheral nerves. The addition of between 5 and 20 mM Ca ions to both CM prevented the reaction but while the addition of Na ions (up to 150 mM) to iopromide had some preventative effect, it did not totally abolish the reaction. In those animals paralyzed with D-tubocurarine, the reaction to iopromide, as observed and recorded by EMG, was the same as that occurring in nonparalyzed animals. This finding is consistent with this reaction being independent of the peripheral nervous system. PMID- 2211042 TI - Neural networks in radiologic diagnosis. I. Introduction and illustration. AB - Artificial neural networks (NNs) process information in a manner similar to the way the human brain is thought to process information. Neural networks have potential application in radiology as an artificial intelligence technique that can provide computer-aided diagnostic assistance for the practicing radiologist. The basic characteristics of NNs and the manner in which information propagates through an NN are discussed in nontechnical language, to assist the diagnostic radiologist in understanding the basic principles of neurocomputing. Computer aided diagnosis selection in pediatric chest radiography using NNs is discussed in a companion article. PMID- 2211041 TI - Comparison of breast consistency at palpation with breast density at mammography. AB - Palpable breast consistency on physical examination was compared with the breast density on mammography for 909 consecutive patients. One of two experienced nurse practitioners palpated each patient's breasts and assigned a consistency value of 1 (little palpable breast consistency) to 4 (maximal palpable breast consistency). Seven mammographers rated the breast density on mammography as either fatty, mild, moderate, or marked parenchymal density for each breast. A low statistical correlation between the two parameters was shown. Thirty-seven percent of markedly dense breasts on mammography was rated only 1 or 2 on palpation. Thus, breast consistency judged by palpation cannot be directly correlated with the density shown on mammography and cannot be used to predict optimal radiographic technique. PMID- 2211043 TI - Neural networks in radiologic diagnosis. II. Interpretation of neonatal chest radiographs. AB - A neural network (NN) system was trained to choose one or more diagnoses from a list of 12 possible diagnoses, based on 21 radiographic observations made on each of a series of neonatal chest radiographs. Initially, an experienced pediatric radiologist provided both the radiographic observations and ranked differential diagnoses for each of 77 neonatal chest radiographs in the preliminary phase used to train the NN. Subsequently, two pediatric radiologists (one of whom provided the initial training-phase data) independently read a series of 103 neonatal chest radiographs (different from the training set) and compiled a list of radiographic findings and differential diagnoses for each radiograph. The trained NN was then asked to provide a list of differential diagnoses for each case from the radiologists' lists of findings. Agreement between the network and each radiologist independently was greater than between the two radiologists. Both the positive and negative agreement between the network and either radiologist was greater than the inter-radiologist agreements for most of the diagnostic endpoints. PMID- 2211044 TI - Variability of myocardial signal on magnetic resonance images. AB - The diagnosis of myocardial disease by magnetic resonance (MR) imaging depends on accurate measurement of myocardial signal intensity. The authors performed 15 experiments in four rabbits at 1.9 T with spin-echo MR imaging to study the variability of myocardial signal intensity throughout the cardiac cycle and to measure myocardial T2 values. Variability in signal from the myocardium throughout the cardiac cycle was observed in all experiments. During systole, a significant increase in myocardial signal was noted, when data acquisition was performed with electrocardiogram (ECG)-gating and controlled ventilation (P = .02). An inverse relationship between myocardial signal and phase noise was found, indicating the motion-related nature of the variation of myocardial signal. A similar inverse relationship was observed in images obtained from a normal human volunteer. Ex vivo myocardial T2 values of rabbit myocardial tissue were significantly higher than the in vivo values (P = .003), reflecting residual motion despite cardiac gating and controlled ventilation. PMID- 2211045 TI - A real-time adaptive ultrasonic imaging system. AB - The performance of an experimental, adaptive, phased array imaging system in improving the quality of abdominal organ images in healthy volunteers was assessed. Trials were conducted under usual clinical imaging conditions and when phase aberrators of known shape and magnitude were introduced into the imaging system. The system, which uses local target brightness as a quality factor, was able to improve clinical image quality when aberrators introduced externally were present and had a negligible effect on image quality when they were not. On several of the volunteers, the phase aberrations were measured directly across the abdomen. The implications of these results for the future clinical application of adaptive imaging systems and the future system modifications are reported. PMID- 2211046 TI - Serial proton magnetic resonance spectroscopy of ischemic brain injury in humans. AB - Four patients were observed serially with 1H magnetic resonance spectroscopy (MRS) at times ranging from 3 days to 10 weeks after a documented ischemic event. Spectra were obtained from 8 cc volumes in infarcted regions and contralateral matched normal regions. Reproducible variations in n-acetyl aspartate (NAA), creatine + phosphocreatine (Cr + PCr), and the sequential changes in lactate and lipid resonances are related to the pathophysiology of stroke. A conspicuous lack of significant change in the choline (Cho) resonance with concomitant decrease in NAA and Cr + PCr is reported as a possible marker of ischemic injury. PMID- 2211047 TI - Computer facilitation of the resident selection process. AB - A personal computer software system has been designed and implemented to facilitate the numerous complex tasks involved in the resident selection process. The computer tracks the status of each candidate, monitors each application for incomplete documentation, generates personalized correspondence, computes and maintains a scoring system based on evaluation by each Resident Selection Committee member, and provides various data printouts (eg, list of candidates by medical school; persons granted an interview; and ranking lists). Developed with the intent to share with the academic community, the system improves organization and accuracy, and notably decreases time spent by administrative assistants and staff members in the resident selection process. PMID- 2211048 TI - We all play in the same sandbox. PMID- 2211049 TI - Noninvasive differentiation of tumors with use of localized H-1 spectroscopy in vivo: initial experience in patients with cerebral tumors. PMID- 2211050 TI - Infant with lethargy, failure to thrive, and abnormal blood smear. PMID- 2211051 TI - Abdominal mass in a four-year-old boy. PMID- 2211052 TI - Comment on the article by Barloon et al, in which hemodilution was found to occur after enteroclysis in patients with partial small bowel obstruction. PMID- 2211053 TI - Magnetic resonance--pathologic correlation. PMID- 2211054 TI - The role of the reference radiologist. Estimates of inter-observer agreement and potential delay in cancer detection in the national breast screening study. AB - The Canadian National Breast Screening Study (NBSS) is a randomized controlled trial to assess the effect of screening on breast cancer mortality. The NBSS designated a single reference radiologist who blindly reviewed over the course of the study 5200 randomly selected two-view mammographic examinations of women not known to have breast cancer. He also reviewed 575 screening-detected breast cancer (SBC) cases and 102 interval breast cancer (IBC) cases. All cancers were histologically proven. As a result of the reviews, comments on inter-observer agreement, interpretation, and technical quality were conveyed on an ongoing basis to radiologists appointed to 15 NBSS screening centers. Agreement of the reference radiologist with center radiologists was better for breast cancer cases (kappa = 0.511, P less than .002) than for those not known to have breast cancer (kappa = 0.307, P less than .002). Observer error and technical problems led to delayed detection in 22% of SBCs and 35% of IBCs. Another 11% of SBCs and 58% of IBCs were probably mammographically occult. No similarly comprehensive review of mammography during a screening program has been published. Suggestions arising from the NBSS review were sometimes resisted by center radiologists. Measures are suggested which might facilitate acceptance of recommendations arising from audit mechanisms in mammography screening programs, thereby enhancing opportunities for mammographic excellence. PMID- 2211055 TI - Surface coil FLASH magnetic resonance imaging of the fasting and secretin stimulated pancreas. AB - The purpose of this study is to investigate the response of the pancreas to secretin stimulation using magnetic resonance imaging (MRI). Using the Siemens 1.0 T Magnetom and a Helmholtz surface coil, single breath FLASH-MRI of the normal fasting pancreas was performed in the prone position, both before and after a 20-minute period after intravenous (IV) bolus injection of secretin (2 cu/kg). T2*-weighted fast low-angle shot sequences (TR = 150 mseconds; TE = 30 mseconds; flip angle = 10 degrees; matrix = 256 X 256; acquisitions = 2) demonstrated an immediate response manifested by a significant distension of the duodenum with fluid secreted by the pancreas, as well as a gradual decline of the pancreas/muscle signal intensity (SI) ratio over time. Twenty minutes after secretin administration, the mean percent decrease of the pancreas/muscle SI ratio in six volunteers was 11.6 +/- 6.4 (1-STD). This is statistically significant (P less than .003) given a mean percent increase of the pancreas/muscle SI ratio of 1.6 +/- 4.8 (1-STD) in five volunteers 20 minutes after bolus injection of saline (control). Although significant duodenal distension is easily demonstrated after secretin administration, the decrease of the relative pancreatic SI over time is visually subtle. Further work is needed to enhance imaging of the physiologic response of the pancreas using even more rapid imaging techniques. PMID- 2211056 TI - Physical and acoustical properties of perfluorooctylbromide, an ultrasound contrast agent. AB - Perfluorooctylbromide (PFOB: C8F17Br) has been shown to be an effective ultrasound contrast agent when incorporated in tissues. The authors have recently demonstrated that PFOB also enhances tissues and Doppler signals during its capillary phase. To help elucidate the physical basis of their observations, the authors compared physical and acoustical properties of standard PFOB-lecithin emulsion with identical lecithin emulsion minus PFOB (vehicle) for concentrations of PFOB from 0% to 50% weight per volume. Propagation velocity, attenuation, and elastic modulus were measured using a 5-MHz source, 0.6-mm hydrophone, and a waveform digitizer, whereas viscosity, density, and particle size were measured directly. Vehicle showed no significant change with increasing concentration in any of the parameters measured. Perfluoroctylbromide exhibited significant linear increase in viscosity and mass density. Increasing concentrations of PFOB emulsion produced a dramatic linear decrease in velocity (r = .99) and a linear increase in attenuation coefficient, (r = .99). Derived values for bulk modulus (reciprocal of compressibility) also showed significant linear decrease (r = .98) with concentration of PFOB. For typical human in vivo blood concentrations of 3.5% PFOB emulsion, the following values were obtained: density, 1.02 g/mL; viscosity, 10.25 cP; velocity, 1450 m/second; attenuation, 2.8 dB/cm; and bulk modulus, 2.18 GPa. Significant differences were found between PFOB and vehicle at even low concentrations, although particle number and size distributions were the same for each, indicating that the presence of PFOB strongly influences acoustic properties. This enhancement was found to be linear over a wide range of concentrations, which supports the possibility of quantitative analysis. PMID- 2211057 TI - Platelet activation and aggregation after endothelial injury. Assessment with indium-111-labeled platelets and angiography. AB - Although platelet activation and aggregation after endothelial injury are well documented, the time course of platelet deposition and the relationship between platelet aggregation and the release of vasoactive products have not been fully clarified in vivo. To study the effect of platelet vasoactive products, a collateral blood supply was induced by ligating the superficial femoral artery in male New Zealand white rabbits. Two weeks later, endothelial injury to the distal abdominal aorta was produced by cytologic brush or mimicked with a metal coil embolus. Platelet aggregation was assessed with indium-111 (111In)-labeled platelets, and scintigraphy demonstrated significant, progressive platelet deposition up to 3 hours after injury and evidence of residual activity 24 hours later. Angiography showed that the time course of peripheral vasoconstriction matched closely that of platelet deposition, indicating release of vasoactive substances from the aggregating platelets. These pathophysiologic changes secondary to endothelial injury may have significant implications for intravascular interventional procedures. PMID- 2211058 TI - Effect of water-soluble contrast medium on the lung in rats. Comparison of iotrolan, iopamidol, and diatrizoate. AB - Aspiration is a serious complication of oral contrast media (CM). The authors investigated the effects of iotrolan, iopamidol, and diatrizoate in rats' lungs. To quantify the lung damage induced by CM, pulmonary water and hemoglobin contents were determined. Arterial blood-gas exchange (pH, PCO2, and PO2) also was determined as an indicator of respiratory function. Iotrolan, iopamidol, or sodium/meglumine diatrizoate with a concentration of 300 mg I/mL was administered intrabronchially at a dose of 1 mL/kg. Physiologic saline was administered to the control group. Ten minutes after administration, arterial blood was collected and the lung was removed. Diatrizoate and iopamidol increased pulmonary water and hemoglobin contents and decreased blood PO2. The effect of iotrolan on these parameters was slight and no significant differences were observed between the iotrolan and saline groups. These results suggest that iotrolan is a preferable CM for gastrointestinal examination in the case of suspected aspiration. PMID- 2211059 TI - Rehabilitation medicine: concepts and trends. PMID- 2211060 TI - Important clarification. PMID- 2211061 TI - Changing attitudes lead to accomplishments. PMID- 2211062 TI - Rehabilitating head injuries. PMID- 2211063 TI - Tribute to rehabilitation medicine. PMID- 2211064 TI - Implications of Cruzan. PMID- 2211066 TI - Public health nursing services. PMID- 2211065 TI - The keys to patient satisfaction. PMID- 2211067 TI - Attempted suicide: a study of 133 cases in Jerusalem. AB - In Israel, each year, an average of 13/100,000 people die by suicide. Attempted suicide has become one of the most important issues for hospital emergency room staff. We studied 133 cases of attempted suicide in Jerusalem in order to examine whether generally accepted risk factors for such attempts are applicable to our local population. We compared the data of 70 patients who attempted suicide and were discharged from the emergency room with those of 63 patients who attempted suicide and were hospitalized in a general hospital. We then compared the characteristics of both groups with those of patients who completed suicide. The study confirmed the hypothesis that the known suicide risk factors of male sex, age over 40 years and a previous psychiatric diagnosis are also valid in this country and must be taken into account when assessing the danger of a suicide attempt. PMID- 2211068 TI - Inefficacy of single-dose nifedipine in the treatment of phobic anxiety. AB - Single-dose nifedipine was given to 13 phobic patients with increased generalized anxiety. Nifedipine failed to demonstrate anxiety-reducing effects on baseline anxiety ratings. Furthermore, in a subset of four patients, the drug failed to show an anxiolytic effect in exposure-related anxiety. PMID- 2211069 TI - Resistant depression. PMID- 2211070 TI - The mind-body problem in contemporary psychiatry. AB - The mind-body problem is important for psychiatry clinically (the problems of interactionism and causality), semantically, and ethically (the problem of causality and free will). It includes the questions: What are minds? Do they exist? Are they ever free? How do they and bodies interact? The author reviews some important answers, in particular the brain-state theory and dualist interactionism, and outlines some implications for psychiatry and for controversies between psychiatry and other mental health disciplines. PMID- 2211071 TI - Child survivors of the Holocaust: psychological adaptations to survival. AB - This paper addresses the means by which children who survived the Holocaust made sense of their survival in later years. Inevitably, these children, now adults, have lived their lives with a series of perplexing questions and fragmented memories. The normal developmental tasks of growing up were mutilated beyond recognition by the traumas of loss and grief, danger and fear, hatred and chaos. The awesome task faced by child survivors included the reconstruction of a terrible past into a sensible present. In order to imbue life with meaning, a sense of continuous self had to be derived from the most fragile and discontinuous beginnings. The authors suggest that over a lifetime the child victim has to struggle with three fundamental questions: 1) Why me? 2) Since it happened to me, how shall I live my life? 3) In living life, what must I do with my grief and my memories? These three inextricable questions are discussed. PMID- 2211072 TI - Rheumatoid arthritis, hypochondriasis, depression and sewing. AB - Six female postmenopausal psychiatric inpatients with rheumatoid arthritis (RA), domineering personality, hypochondriasis, alexithymia and perfectionism are presented. None of the patients fully responded to antidepressant drug treatment. Five of the six women were professionally engaged in sewing, which might be considered a mechanical risk factor for rheumatoid arthritis. Several psychiatric aspects of RA are discussed, particularly the existence of the "arthritic personality" and the influence of psychological stress in RA patients. PMID- 2211073 TI - Exercise and sport in mental health: a review of the literature. AB - A literature survey was conducted of the most prominent psychological effects and therapeutic applications of physical activity in mental health. This paper primarily reviews the literature comparing therapeutic exercise and sport with more traditional therapies and activities. Commentary on research methods is also presented. PMID- 2211074 TI - Can theology have a role in "public" bioethical discourse? PMID- 2211075 TI - Bioethics and the contemporary Jewish community. PMID- 2211076 TI - What can religion offer bioethics? PMID- 2211077 TI - Religion and the secularization of bioethics. PMID- 2211078 TI - Talking of God--but with whom? PMID- 2211079 TI - Religion and moral meaning in bioethics. PMID- 2211080 TI - Biomedicine and technocratic power. PMID- 2211081 TI - The ethics of teaching ethics. PMID- 2211082 TI - Medical joint-venturing: an ethical perspective. PMID- 2211083 TI - Foreclosing the use of force: A.C. reversed. PMID- 2211084 TI - State interests re-examined. PMID- 2211085 TI - AIDS activism. PMID- 2211086 TI - Linking choice with AIDS. PMID- 2211087 TI - Risks of consent. PMID- 2211088 TI - Geneticists and sex selection. PMID- 2211089 TI - Whither the genome project? PMID- 2211091 TI - Professional ethics. PMID- 2211090 TI - The argument for unlimited procreative liberty: a feminist critique. PMID- 2211092 TI - Re: News and notes by Henry Yokoyama, HMJ June 1990. PMID- 2211093 TI - Professional ethics in health care: an introduction. AB - Discussions about issues in medical ethics are often frustrated by the failure to distinguish other concerns: legal and institutional rules, personal values, and personal moralities. Progress can be made if the medical profession reaches a prior agreement on its core values--what the good physician ought to care about- and a consensus on how these values are to be respected by physicians facing ethical dilemmas. PMID- 2211094 TI - L-tryptophan-related eosinophilia-myalgia syndrome: a case report. AB - Eosinophilia-myalgia syndrome (EMS) is characterized by intense eosinophilia and, very often, debilitating generalized myalgia in the absence of infectious or neoplastic causation. The Centers for Disease Control have established that the latter two features, along with an eosinophil count greater than 1000 cells per cu mm, are criteria for the syndrome. EMS has been reported in epidemic proportions over the last several months. Early data strongly suggested that in at least a small percentage of patients the syndrome leads to death. Epidemiological work in New Mexico, Minnesota, and Oregon has linked EMS most impressively to L-tryptophan-containing products (LTCPS). PMID- 2211095 TI - Outcome following open-heart surgery in an Oriental octagenarian population in Hawaii. AB - Increasingly, a surgical approach is being utilized for the management of elderly patients with ischemic or valvular heart disease. In order to further understand the outcome in this population, we performed a retrospective review of octagenarians undergoing open-heart surgery over a 2-year period. Thirteen patients were identified, with a mean age of 82.6 years. All were Oriental. Most of our patients were considered high risk, 10 of them requiring emergency surgery and 6 requiring preoperative intra-aortic balloon counterpulsation (IABP). Postoperatively, 11 of the 13 patients suffered at least 1 complication. The most frequent complications were atrial arrythmias (7 patients), a low cardiac output (5 patients), the need for prolonged ventilation (3 patients) and ventricular arrythmias (3 patients). Functionally, the patients statistically improved, from a mean preoperative classification of 3.8 (New York Heart Association Classification) (NYHA) to 1.5 at the time of discharge (p less than 0.001). All patients are still alive at the time of writing (October 1989) with a mean followup of 13.3 months. Our data show that an operative approach to heart disease can be done safely in a high risk octagenarian population. In addition, we found that a statistically significant functional improvement occurred in these patients. PMID- 2211096 TI - Chance, the prepared mind and children with Hansen's disease. AB - 1. Hansen's Disease is a chronic disease found in every continent in the world and among all ethnic groups. 2. Hawaii is neither a "hotbed" of the disease nor a place where the disease is absent. 3. Hansen's Disease is endemic in these islands, but we also have problems and resources for coping with it. 4. Current treatment approaches to clinical and public health aspects of the disease now offer hope. 5. There is a continuing need to educate patients, families, communities and professional workers in the many aspects of this disease. 6. Opportunity exists for Hawaii to become the training nucleus for medical and public health approaches to Hansen's Disease among the populations of the Pacific Basin. PMID- 2211097 TI - Reconstruction of complex maxillectomy defects with the scapular-free flap. AB - The defect resulting from partial or complete maxillectomy can often be reconstructed with a skin graft and a prosthesis. In situations where this simple maneuver is unsatisfactory, a more complex reconstructive modality, providing the restoration of composite tissue, is required. The scapular microvascular-free flap was used in this series of 11 patients, as a cutaneous flap in 3 and as an osteocutaneous flap in 8, to meet the specific reconstructive needs of each patient. Excellent to satisfactory restoration of facial contour and palatal function was achieved in 10 patients. There was 1 flap failure. There were no donor site complications. Selected case histories are presented to demonstrate a spectrum of reconstructive problems. There are clear limitations to its applicability, such as the odd scapular bone contour, the thickness of the cutaneous paddle, the position change required for flap harvesting, and the risk of flap failure. The scapular flap has proven to be useful in restoring bony and soft tissue contour of the face, rigid support for the velum, oronasal separation, support for the orbit, and obliteration of the maxillary sinus. We found the scapular-free flap to be a useful tool for reconstructing complex and variable maxillectomy defects. PMID- 2211098 TI - Folded, bipaddled composite flap in head and neck reconstruction. AB - A series of 34 patients repaired by folded, bipaddled composite flaps for head and neck cancer surgical defects is presented. Pectoralis major composite flap was used in 33 patients on musculovascular pedicle and 1 patient had a latissimus dorsi composite flap free-tissue transfer. The pectoralis major rib, osteomyocutaneous flap was utilized in 6 patients who had lesions of the mouth floor and anterior mandibular arch. The incorporated rib was used as a vascularized bone graft for the stability of mandibular fragments. Thus, one regional composite flap used in bipaddled fashion enabled the reconstruction of mucosal, skin, and mandibular arch defects. PMID- 2211099 TI - Botulinum A toxin for the treatment of spasmodic torticollis: dysphagia and regional toxin spread. AB - Chemodenervation of cervical muscles with botulinum A toxin, although useful in treating spasmodic torticollis, has been associated with dysphagia. Retrospective analysis of dose and injection site (sternomastoid vs. posterior cervical muscle groups) in 26 patients (49 injections) suggested that dysphagia was related to the quantity of toxin injected into the sternomastoid muscle: dysphagia, median 150 IU (7 injections); and no dysphagia, median 100 IU (42 injections; p = 0.026 Wilcoxon test). In a prospective study (31 injections to 24 patients), limiting the dose administered to the sternomastoid to 100 IU, substantially reduced the incidence of dysphagia (0 of 31, p = 0.27, Fisher's exact test). Denervation of human orbicularis muscle fibers, 5 weeks to 4 months after injection of botulinum A toxin for the treatment of blepharospasm, was successfully demonstrated by intense, diffuse acetylcholinesterase staining. A weight-adjusted dose similar to that given for torticollis was injected into longissimus dorsi muscle in 6 albino rabbits. Using the acetylcholinesterase stain as a marker, a diffusion gradient was noted over a distance of 30 to 45 mm from the point of injection and in contralateral muscle 15 to 25 mm from this point. Thus, denervation was demonstrated to occur within a definable area which crossed anatomic barriers, such as fascia and bone. These clinical and laboratory data suggest that dysphagia following botulinum toxin therapy results from toxin spread to pharyngeal musculature from the sternocleidomastoid injection site. Limiting of the injection dose to 100 IU or less to the sternomastoid substantially decreases the incidence of this complication. PMID- 2211100 TI - Basement membrane type IV collagen in oral squamous cell carcinoma. AB - Biopsied specimens of 82 oral squamous cell carcinomas were immunohistochemically studied for detection of type IV collagen existence in the basement membrane (BM). Immunoreactivity on BM was semiquantitatively evaluated as limited (+/-), moderate (+), or extensive (+ +), and matched against clinical and histopathologic features. No clear difference in BM deposition could be found in the tumor sites. The amount of type IV collagen decreased in advanced T stage (T3 and T4) tumors. BM deposition was significantly correlated with lymph node metastasis. In 54 N-, 32 had extensive deposition, 18 had moderate, and the remaining had limited. Conversely, only 5 of 28 N+ cases showed good type IV collagen immunoreactivity and 14 cases exhibited limited BM deposition. BM existence was also associated with the mode of invasion. BM deposition decreased in order with the grade (i.e., the more limited the BM deposition, the more diffuse the invasion mode). BM deposition was, however, not related with stromal responses, such as cellular infiltrates and fibrosis. We conclude that immunohistochemical examinations of BM deposition on biopsied specimens seem beneficial for cancer treatment. PMID- 2211101 TI - Histologic differentiation and chemosensitivity of human head and neck squamous cell carcinomas. AB - The chemosensitivities of 42 human head and neck squamous cell carcinomas were examined using the in vitro succinate dehydrogenase inhibition (SDI) test. The tumor tissues obtained at surgery or biopsy were exposed to five different antitumor drugs: adriamycin (ADM), cisplatin (CDDP), carboquone (CQ), 5 fluorouracil (5-FU), and 1-hexylcarbamoyl-5-fluorouracil (HCFU). The results were analyzed according to the histopathologic degree of differentiation of well, moderately, and poorly differentiated squamous cell carcinoma. The average decrease in succinate dehydrogenase activity was 43.2 +/- 24.9 for ADM, 29.0 +/- 14.2 for CDDP, 32.9 +/- 17.6 for CQ, 64.2 +/- 20.6 for 5-FU, and 26.8 +/- 16.9 for HCFU. There was a statistically significant difference in the decrease of succinate dehydrogenase activity between well and poorly differentiated squamous cell carcinomas. These data suggest that, for patients with a poorly differentiated squamous cell carcinoma, the response to anti-cancer drugs may be more satisfactory than in those with a well-differentiated squamous cell carcinoma. PMID- 2211103 TI - Accessory parotid glands as a site of metastases from outside the head and neck: case report. AB - Metastases to the salivary glands from outside the head and neck are rare. The world literature reports 53 cases to the parotid, and 25 to the submandibular submaxillary gland. This is the first report of a metastasis to the accessory parotid gland. PMID- 2211102 TI - Investigation of urinary transforming growth factor alpha levels as tumor markers in patients with advanced squamous cell carcinoma of the head and neck. AB - The objective of this study was to determine whether transforming growth factor alpha (TGF alpha) levels could be used as nonspecific tumor markers in patients with advanced squamous cell carcinoma (SCC) of the head and neck. Fourteen patients with epidermoid carcinoma of the head and neck were followed with serial urine TGF alpha levels, and the results were compared with the extent of cancer and the course of the disease. Based on the findings of this study further research is necessary before urine TGF levels can be recommended as a routine screening test for SCC of the head and neck. PMID- 2211104 TI - Metastatic involvement of the cavernous sinus from primary pharyngolaryngeal tumors. AB - The cavernous sinus is an unusual site for metastases from tumors of the larynx and pharynx. In postmortem studies of patients with cancers of the larynx, hypopharynx, and other sites, cavernous sinus metastases have been detected in very few cases. We present 3 cases of metastatic cavernous sinus disease. Despite the lack of pathologic diagnosis by biopsy, we feel that the clinical presentation combined with computed tomography provides an accurate diagnosis. PMID- 2211105 TI - Sternocleidomastoid flap following parotidectomy. AB - The sternocleidomastoid (SCM) muscle has been used in various ways for reconstruction following cancer resections in the head and neck. Its use has been restricted because of the presumed precarious nature of its blood supply and its proximity to disease. Patients with large or recurrent benign parotid tumors were the first in our series to have a SCM muscle flap (either superiorly or inferiorly based) used to improve cosmesis. After demonstrating the utility of these flaps, we extended the indications for their use to include patients with primary or recurrent malignant disease. The flaps provide soft tissue contour, coverage of facial nerves and nerve grafts, act as a healthy bed for skin grafts, and help close salivary fistulas. There were no complications attributed to the flaps. This paper discusses 31 patients with benign and malignant parotid disease in whom the SCM flap was used. PMID- 2211106 TI - Tracheal neurilemmoma: case report and review of the literature. AB - We report a rare case of an intratracheal neurilemmoma which presented as advanced upper airway obstruction. The tumor was successfully excised by laryngofissure. A review of the world literature is provided. PMID- 2211107 TI - Cervical metastatic squamous carcinoma of unknown or occult primary source. AB - Whether to accept the report of the referring physician is often a stumbling block for many otolaryngologist-head and neck surgeons, especially when management of the case is changing hands. Thus, it is no surprise that all the consultants would repeat the examination of the upper aerodigestive tract under anesthesia. Drs. Robbins and Fried objected to the term "blind" biopsies and preferred "random-guided" and "directed" biopsies is that order. Yet, all 3 specialists agree that multiple biopsies of Waldeyer's ring should be obtained. They emphasize that palpation is an integral part of the endoscopy and may guide the surgeon in deciding where to biopsy. The surgeons agree that the base of tongue has the highest yield in cases like this one. Dr. Robbins stands alone in his use of ipsilateral tonsillectomy as a screening biopsy technique. Dr. Robbins believes imaging studies have a role prior to the initial panendoscopy and prefers an MRI of the head and neck. Drs. Gluckman and Fried use imaging studies if the primary tumor is in a clinically difficult area to evaluate. Faced with a normal repeat endoscopy and no other cervical adenopathy, Drs. Fried and Robbins would treat Waldeyer's ring and both sides of the neck with radiotherapy; Dr. Fried suggests 60 to 65 Gy over 6 weeks and Dr. Robbins suggests 65 to 70 Gy over 6 to 7 weeks to Waldeyer's ring and the upper neck but would treat the remaining nodal areas of the neck with 50 Gy over 5 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2211108 TI - Evaluation of environmental radiation exposures from nuclear testing in Nevada: a symposium. Proceedings. PMID- 2211109 TI - Overview of the Department of Energy's Off-Site Radiation Exposure Review Project (ORERP). AB - The Off-Site Radiation Exposure Review Project (ORERP) was established by the U.S. Department of Energy to (1) collect, preserve, and disseminate historical data related to radioactive fallout and health effects from nuclear testing, and (2) reconstrut, insofar as possible, the exposures to the off-site public from nuclear testing at the Nevada Test Site and doses to individuals resulting from these exposures. The goals, methods, and example results of the ORERP are presented. PMID- 2211110 TI - Overview of the National Cancer Institute's activities related to exposure of the public to fallout from the Nevada Test Site. AB - The Department of Health and Human Services (DHHS) was directed by Congress to assess the risk of thyroid cancer from 131I associated with fallout from the atmospheric testing of nuclear weapons at the Nevada Test Site. The National Cancer Institute (NCI) was requested by DHHS to address Public Law 97-414, Section 7 (a), which directs DHHS to "(1) conduct scientific research and prepare analyses necessary to develop valid and credible assessments of the risks of thyroid cancer that are associated with thyroid doses of Iodine 131; (2)...develop...methods to estimate the thyroid doses of Iodine 131 that are received by individuals from nuclear bomb fallout; (and) (3)...develop...assessments of the exposure to Iodine 131 that the American people received from the Nevada atmospheric nuclear bomb tests." In addition, the University of Utah, under contract with the NCI, is carrying out a study to determine if the incidence of thyroid disease and leukemia among identified populations in Utah may be related to exposure from fallout originating at the Nevada Test Site. PMID- 2211111 TI - Additional calculations of radionuclide production following nuclear explosions and Pu isotopic ratios for Nevada Test Site events. AB - A method is reviewed for calculating dry ground deposition of any radionuclide in off-site fallout from a nuclear explosion. Calculations are in agreement with measurements. A list of all calculations to date is presented, along with how to obtain copies. In addition, a table of ratios of 240Pu:239Pu and 241Pu:239Pu for NTS explosions is included. PMID- 2211112 TI - Historical estimates of external gamma exposure and collective external gamma exposure from testing at the Nevada Test Site. II. Test series after Hardtack II, 1958, and summary. AB - The historical data on the cumulative individual external gamma exposures are tabulated for communities around the Nevada Test Site for the time periods of 1961 to the signing of the Limited Test Ban Treaty on 5 August 1963, and from then until 1975. The collective exposures during the two time periods are calculated to be 610 and 320 person-R, respectively. The total collective external gamma exposure from 1951 through 1975 for these communities s calculated to be 86,000 person-R. The area considered includes the countries of Clark, Lincoln, Nye, and White Pine in Nevada and the countries of Iron and Washington in Utah; inclusion of Salt Lake City would have substantially increased the calculated collective exposure because of the large population. The methods of calculation are reviewed. Also, the historical data on the assessment of dose via ingestion are reviewed with emphasis on the dose to the thyroid of infants living in St. George, UT, at the time of fallout from event HARRY on 19 May 1953. PMID- 2211113 TI - Ground-based air-sampling measurements near the Nevada Test Site after atmospheric nuclear tests. AB - Historical air-sampling data measured within 320 km (200 mi) of the Nevada Test Site (NTS) have been reviewed for periods following atmospheric nuclear tests, primarily in the 1950s. These data come mostly from high-volume air samplers, with some from cascade-impactor samplers. Measurements considered here are for beta radiation from gross fission products. The resulting air-quality data base is comprised of almost 13,000 samples from 42 sampling locations downwind of the NTS. In order to compile an accurate air-quality data base for use in estimating exposure via inhalation, raw data values were sought where possible, and the required calculations were performed on a computer with state-of-the-art algorithms. The data-processing procedures consisted of (1) entry and error checking of historical data; (2) determination of appropriate background values, air-sampling volumes, and net air concentrations; and (3) calculation of integrated air concentration (C) for each sample (considering fallout arrival times). Comparing C values for collocated high-volume and cascade-impactor samplers during the Upshot-Knothole series showed similar lognormal distributions, but with a geometric mean C for cascade impactors about half that for the high-volume air samplers. Overall, the uncertainty in C values is about a factor of three. In the past, it has been assumed that C could be related to ground deposition by a constant having units of velocity. In our data bases, simultaneous measurements of air concentration and ground deposition at the same locations were not related by a constant; indeed, there was a great amount of scatter. This suggests that the relationship between C and ground deposition in this situation is too complex to be treated adequately by simple approaches. PMID- 2211114 TI - Radioactive fallout reconstruction from contemporary measurements of reservoir sediments. AB - The temporal history of atmospheric deposition to a watershed area can be preserved in the sediment of a lake or reservoir that is supplied by the watershed. The 137Cs and isotopic Pu concentrations with depth were determined in the sediments of two reservoirs, Enterprise and Deer Creek, which are located in widely separated regions of the state of Utah. Our data not only reconstruct the history of the total radioactive fallout in the area, but also permit estimating the contributions from global sources and from the Nevada Test Site detonations in the 1950s. PMID- 2211115 TI - Estimates of exposure rates and fallout arrival times near the Nevada Test Site. AB - One of the tasks of the Off-Site Radiation Exposure Review Project (ORERP) was to estimate doses to individuals resulting from exposure to fallout from nuclear testing at the Nevada Test Site (NTS). Dose estimates are based on estimates of the exposure rate 12 h post-detonation (H + 12) and the time of fallout arrival from events producing discernible fallout at locations off the NTS. These estimates are derived from both published fallout patterns and survey meter readings taken by monitors in the field. Each fallout pattern is digitized, and kriging is used to interpolate estimates of exposure rate and arrival time onto a 10-km grid covering the contours of the pattern. These grid values are then used to calculate estimates at any location of interest within the pattern. Exposure rate is also estimated from the survey meter readings for a particular nuclear event by decay-correcting the measurements near a selected location to H + 12 and then aggregating them into one estimate. Estimates of discernible exposure rate and time of fallout arrival from 74 nuclear events at the NTS are contained in the Town Data Base. Estimates are given for 352 locations in Arizona, California, Nevada, and Utah. Each record in the data base contains estimates for a specified event and location. The distribution of exposure rate is represented by a geometric mean and standard deviation; the distribution of fallout arrival time is represented by an arithmetic mean and standard deviation. A more extensive description and a listing of the Town Data Base are included in a separate report. PMID- 2211116 TI - Estimates of fallout in the continental U.S. from Nevada weapons testing based on gummed-film monitoring data. AB - During periods of weapons testing at the Nevada Test Site (NTS) between 1951 and 1958, the Environmental Measurements Laboratory (EML) monitored daily fallout at about 100 sites in the U.S. using gummed-film collectors. These gummed-film data represent the only comprehensive set of actual measurements of fallout during this period for areas outside the immediate vicinity of the NTS. The measured beta activities originally reported by EML have been reviewed and reevaluated. This reevaluation corrected a number of errors in the original data set and allowed fairly accurate estimates to be made of specific radionuclide depositions from individual NTS shots. Estimates of the geographical and temporal variations in cumulative 137Cs and 131I depositions from all NTS shots through 1957 are presented, as well as estimates of the relative impact of particular shots and test series. The revised gummed-film estimates of total NTS fallout depositions are compared with estimates based on contemporary and historical soil sample analyses. These reevaluated gummed-film fallout deposition estimates are being extensively utilized in a number of ongoing programs to reconstruct the radiation exposure of the U.S. population from Nevada weapons testing. PMID- 2211117 TI - Analysis of meteorological and radiological data for selected fallout episodes. AB - The Weather Service Nuclear Support Office has analyzed the meteorological and radiological data collected for the following atmospheric nuclear tests: TRINITY; EASY of the Tumbler-Snapper series; ANNIE, NANCY, BADGER, SIMON, and HARRY of the Upshot-Knothole series; BEE and ZUCCHINI of the Teapot series; BOLTZMANN and SMOKY of the Plumbbob series; and SMALL BOY of the Dominic II series. These tests were chosen as having the greatest impact on nearby downwind populated locations, contributing approximately 80% of the collective estimated exposure. This report describes the methods of analysis used in deriving fallout-pattern contours and estimated fallout arrival times. Inconsistencies in the radiological data and their resolution are discussed. The methods of estimating fallout arrival times from the meteorological data are described. Comparisons of fallout patterns resulting from these analyses with earlier analyses show insignificant differences in the areas covered or people exposed. PMID- 2211118 TI - Meteorological modeling of arrival and deposition of fallout at intermediate distances downwind of the Nevada Test Site. AB - A three-dimensional atmospheric transport and diffusion model is used to calculate the arrival and deposition of fallout from 13 selected nuclear tests at the Nevada Test Site (NTS) in the 1950s. Results are used to extend NTS fallout patterns to intermediate downwind distances (300 to 1200 km). The radioactive cloud is represented in the model by a population of Lagrangian marker particles, with concentrations calculated on an Eulerian grid. Use of marker particles, with fall velocities dependent on particle size, provides a realistic simulation of fallout as the debris cloud travels downwind. The three-dimensional wind field is derived from observed data, adjusted for mass consistency. Terrain is represented in the grid, which extends up to 1200 km downwind of NTS and has 32-km horizontal resolution and 1-km vertical resolution. Ground deposition is calculated by a deposition-velocity approach. Source terms and relationships between deposition and exposure rate are based on work by Hicks. Uncertainty in particle size and vertical distributions within the debris cloud (and stem) allow for some model "tuning" to better match measured ground-deposition values. Particle trajectories representing different sizes and starting heights above ground zero are used to guide source specification. An hourly time history of the modeled fallout pattern as the debris cloud moves downwind provides estimates of fallout arrival times. Results for event HARRY illustrate the methodology. The composite deposition pattern for all 13 tests is characterized by two lobes extending out to the north northeast and east-northeast, respectively, at intermediate distances from NTS. Arrival estimates, along with modeled deposition values, augment measured deposition data in the development of data bases at the county level; these data bases are used for estimating radiation exposure at intermediate distances downwind of NTS. Results from a study of event TRINITY are also presented. PMID- 2211119 TI - Meteorological modeling of radioiodine transport and deposition within the continental United States. AB - A meteorological transport and deposition interpolation model has been employed to estimate radioiodine deposition remote from the Nevada Test Site between points of observed deposition. The movement of the radioactive cloud across the United States is obtained from wind trajectories at various quasi-constant levels up to the top of the initial radioactive cloud. This model deals primarily with depositions beneath the passing cloud that are associated with precipitation. The fraction of radioiodine scavenged was inferred from a relationship derived statistically from fallout at locations having wet deposition. Therefore, estimation of deposition at locations between fallout observations is possible wherever precipitation occurred under the cloud. These estimates use very detailed historical records of precipitation available for virtually every county in the United States. Because significant dry and wet depositions also occur in areas that are not beneath the cloud, interpolation methods, such as kriging, are used to estimate fallout between the radioactivity observation locations. Ground level radioactivity measurements are required for these alternative methods. Such observations are validated before being used, often by the use of supplementary low-level trajectories. PMID- 2211120 TI - Pasture practices, milk distribution, and consumption in the continental U.S. in the 1950s. AB - Determining the consumption of milk contaminated with 131I, resulting from atmospheric nuclear weapons tests conducted at the Nevada Test Site, by the United States population during the 1950s constitutes one part of the methodology used by the National Cancer Institute to assess radiation exposures to Americans. In order to make these estimates for locations throughout the United States, it is necessary to determine the pasture intake by cows and the distribution of the milk produced for human consumption at times when the weapons were tested. Since the milk industry has undergone many changes during the past 35 y, historical records and information must be used. The methodology developed to estimate the intake of contaminated pasture by dairy cows, milk production, and milk distribution on a county basis for the continental U.S. during the 1950s is described in detail. The relevant data on milk consumption by humans are also discussed. PMID- 2211121 TI - Milk distribution and feeding practice data for the PATHWAY model. AB - Milk is a major source for ingestion of several radionuclides, particularly when it is produced from fresh forage. Estimation of radionuclide ingestion via milk from Nevada Test Site fallout events in the 1950s required information on the sources of milk, feeding practices for cows, and elapsed time between milking and consumption for various geographic areas. These data were essential input to the food-chain model, PATHWAY. A data base was compiled from personal interviews. Milk sources included private cows, local dairies, and regional plants that collected from and distributed to wide geographic areas. Estimates of the contribution of each source were made for communities in a nine-state area. Pasture seasons varied from 3 to 6 mo. Pasture use varied from zero to 80% of the cows' diet. Pasture use declined during the 1950s, as did the number of family cows and local dairy plants. Regional distributors captured a larger portion of the market, and improved technologies increased the shelf life of milk. These factors tended to reduce the human intake of fallout radionuclides from milk in the latter part of the 1950s. PMID- 2211122 TI - Estimation of radionuclide ingestion: the "PATHWAY" food-chain model. AB - This paper describes the structure of the dynamic food-chain model PATHWAY and its utility for estimating radionuclide ingestion after fallout deposition from nuclear testing in Nevada. Model input requirements are described and output examples are provided. The basic output of PATHWAY is the time-integrated radionuclide ingestion by humans per unit fallout deposition (Bq per Bq m-2). Output specific to sex, age, life-style (diet), location (agricultural practice), event (calendar date), and radionuclide may be generated. Uncertainties of model predictions, based on "Monte Carlo" simulations using parameter value distributions, are described. Results of a sensitivity analysis, based on a ranking of partial correlation coefficients, are reviewed to illustrate the relative importance of parameters and associated transport pathways. Output data for 131I and 137Cs in milk are compared with predictions from several well known food-chain models. Preliminary efforts to validate PATHWAY results with real data sets are described. PMID- 2211123 TI - Development of a method to estimate thyroid dose from fallout radioiodine in a cohort study. AB - A cohort of 4831 persons aged 11-18 y in 1965 was identified among students in the schools of Washington County, UT; Lincoln County, NV; and Graham County, AZ. These children who had potentially been exposed to radioiodine from atomic weapons test fallout from the Nevada Test Site during 1951-1962 were selected for participation in a study of thyroid disease. The entire cohort was first examined during 1965-1968 for thyroid abnormalities. A total of 3,085 of these people were again reexamined during 1985-1986 to determine any subsequent occurrence of thyroid disease. In order to determine the relationship of the radiation dose to the thyroid with incidence of thyroid disease, we have developed a suite of models to calculate estimates of the internal dose received by the thyroid from fallout radioiodines. For completeness, the exposure to the thyroid from external radiation is also estimated. Dose estimates are made specific to each individual in the study using individual residential histories, the locality-specific exposure rate and radionuclide deposition, descriptions of dairy management for identified milk producers, and the subjects' sources of foods and intake rates of milk and leafy vegetables determined by interview. Other data such as the relationship of radioiodine deposition to measured exposure rate, environmental transfer parameters, and age-dependent factors for the conversion of radioiodine intake to thyroid dose were taken from work of other investigators. Dairy management information, milk distribution practices, the milk source for each study subject, as well as age-specific intake rates of milk and leafy vegetables, were determined by interview. PMID- 2211124 TI - ORERP (Off-Site Radiation Exposure Review Project) internal dose estimates for individuals. AB - A method was developed to reconstruct the internal radiation dose to off-site individuals who were exposed to fallout from nuclear weapons tests at the Nevada Test Site (NTS). By this method, committed absorbed doses can be estimated for 22 target organs of persons in four age groups and for selected organs of the fetus. Ingestion doses are calculated by combining age-group dose factors and intakes specific for age group, test event, and location as calculated by the PATHWAY food-chain model. Inhalation doses are calculated by combining age-group dose factors and breathing rates, and time-integrated air concentrations that are derived from the ORERP Air-Quality Data Base. Dose estimates are calculated for the radionuclides that contribute significantly to the total dose; these number 20 via the ingestion pathway and 46 via the inhalation pathway. Internal doses to nonspecified individuals and nonspecified fetuses are being reconstructed for each location in the ORERP Town Data Base for which exposure rates and cloud arrival times are listed. Examples of reconstructing internal dose are presented. This method will also be adapted to reconstruct internal doses from NTS fallout to specific individuals in accordance with the person's age, past residence, life style, and living pattern. PMID- 2211125 TI - External exposure estimates for individuals near the Nevada Test Site. AB - Individuals living near the Nevada Test Site were exposed to both beta and gamma radiations from fission products and activation products resulting from the atmospheric testing of nuclear devices. These exposures, and the resultant doses, were functions of the amount of material deposited, the time of arrival of the debris, and the amount of shielding afforded by structures. Results are presented for each of nine generic life-styles. These are representative of the living patterns of people residing in the area. For each event at each location for which data exist, a representative of each life-style was closely followed for 30 d. The results of these detailed calculations were then extrapolated to the present, employing a stochastic model. Results displayed are the geometric means and standard deviations derived from 25 independent determinations of the various quantities shown. For each determination, required parameters were randomly selected from appropriate distributions. Calculations yielded estimates for: 1) whole-body and skin dose due to gamma rays from material on the ground; 2) skin dose due to beta particles from material deposited directly on the skin; and 3) skin dose due to beta particles from material deposited on the ground. Organ dose estimates were established from the whole-body dose using appropriate conversion factors. For the homemaker life-style, the uterus dose was also calculated as a function of time for 9 mo. This assisted in estimating fetal dose as a function of gestation. PMID- 2211126 TI - Individual external exposures from Nevada Test Site fallout for Utah leukemia cases and controls. AB - External gamma-ray exposures from fallout originating at the Nevada Test Site (NTS) have been assigned to 6,507 individual subjects (1,177 leukemia cases and 5,330 control subjects) who died as Utah residents between 1952 and 1981. Leukemia cases were identified, confirmed, and classified by cell type from the Utah Cancer Registry, Utah State vital records, and medical records. Residential histories were obtained from the Deceased Membership File (DMF) of the Church of Jesus Christ of Latter-day Saints (LDS), supplemented by information from the LDS Church Census Records that were taken in 1950, 1955, and 1960-62. Control subjects were selected randomly within age strata from the DMF and were frequency matched to the cases by age at death and for sex. Individual radiation exposures were assigned as a function of residence location and time interval for each residence during the fallout period (1951-1958) using geographic exposure data taken from the literature. Temporal distribution of exposure for subjects who resided in more than one locality or who were born or died during the fallout period was determined from data of other investigators. Calculated gamma-ray exposures for each place of residence were summed for each subject to yield the exposure to fallout from the NTS. PMID- 2211127 TI - Cohort study of thyroid disease near the Nevada Test Site: a preliminary report. AB - The atmospheric testing of nuclear weapons in Nevada beginning in 1951 resulted in exposure of regions surrounding the Nevada Test Site (NTS) to fallout. A cohort of children born between 1947 and 1954 in two counties near the NTS, one in Utah and one in Nevada (UT/NV), were examined in 1965-1968 for thyroid abnormalities that might have been a result of exposure to radioiodine in fallout. The prevalence of thyroid abnormalities in these children (11-18 y) was compared to that in a control group selected from a county in Arizona (AZ) that was presumed to have received little or no fallout from the NTS. Thyroid nodules were found in 76 of the 4,819 children examined (15.8/1000). Of the 76 thyroid nodules, 22 were diagnosed as neoplasms. The rate of thyroid neoplasms among the UT/NV subjects was higher (5.6/1000) than among the AZ subjects (3.3/1000) (RR = 1.7), but because the number of neoplasms was small, the difference was statistically insignificant. In 1985-1986, 3,122 of the original study subjects were reexamined. In this reexamination, thyroid nodules were found in 125 individuals (44.2/1000). Of the 125 thyroid nodules detected during this later study period, 65 were considered to be thyroid neoplasms. Rates of thyroid neoplasms in UT/NV (24.6/1000) are again slightly higher than in AZ (20.2/1000) (RR = 1.2), but the difference is not significant (p = 0.65). Based on the rates of thyroid neoplasms in the two geographic locations, we conclude that living near the NTS in the 1950s has not resulted in a statistically significant increase of thyroid neoplasms in subjects from UT/NV when compared with subjects of the same age and gender living in AZ. PMID- 2211128 TI - Strategic change in hospitals: an examination of the response of the acute care hospital to the turbulent environment of the 1980s. AB - Changes in strategies of hospitals responding to the turbulent health care environment of the 1980s are examined both in the aggregate and from the perspective of the individual hospital. The Miles and Snow typology is used to determine strategy type. Both investor-owned and not-for-profit hospitals were well represented in the broad mix of hospital types sampled. In addition, freestanding hospitals and members of multihospital systems were present in the sample. Last, hospitals of all sizes were included. Strategic change was evaluated by classifying hospitals by strategy type in each of two consecutive five-year time periods (1976 through 1980 and 1981 through 1985). Changes in reimbursement policies, the emergence of new technologies, changing consumer expectations, and new sources of competition made the environment for hospitals progressively more turbulent in the latter period and provided an opportune setting to evaluate strategic change. Results showed that a significant number of hospitals did change strategy as the environment changed, and in the direction anticipated. Logistic regression was used to determine whether prior strategy, type of ownership, system membership, or size would predict which hospitals would change strategy as the environment changed: only prior strategy was found to be a predictor of strategy change. PMID- 2211129 TI - Do HMOs reduce health care costs? A multivariate analysis of two Medicare HMO demonstration projects. AB - Charge data from two Medicare HMO demonstration projects were analyzed to determine if prepaid plans achieved cost savings for enrolled beneficiaries. Fallon Community Health Plan of Massachusetts did not reduce total charges significantly for survivors in their first year postenrollment. However, the plan enjoyed reductions in total charges per month after the first year of nearly 38 percent (41 percent for Part A; 31 percent for Part B). Savings for decedents were more modest, reducing total charges per month by around 27 percent (19 percent, Part A; 68 percent, Part B). Greater Marshfield Community Health Plan of Wisconsin was not successful in controlling charges during the demonstration period. Marshfield incurred losses in the first postenrollment year for survivors due to a 38 percent increase in total charges per month (18 percent, Part A; 73 percent, Part B). In the second year postenrollment, the Marshfield plan was able to reduce losses for survivors to roughly 11 percent (-6 percent, Part A; 44 percent, Part B). For decedents, Marshfield experienced an increase in total charges per month of approximately 21 percent relative to fee-for-service comparisons, with Part B charges again much higher than those of the comparison group (47 percent). PMID- 2211130 TI - The effects of a prepaid group practice on mental health outcomes. AB - Does a prepaid group practice relative to comparable fee-for-service plans lead to different mental health outcomes for its beneficiaries? To answer this question, we used data from the RAND Health Insurance Experiment. We observed no statistically significant or clinically meaningful differences in mental health outcomes for families randomly assigned to Group Health Cooperative of Puget Sound or to comparable fee-for-service insurance plans in the Seattle area. We found the same null result for overall mental health status as well as for psychological distress (e.g., anxiety and depression) and psychological well being, and for the full population as well as the initially sick and poor, although our precision was low for the latter comparisons. Thus, the less intensive style of treatment in the prepaid group practice was not associated with noticeably worse mental health outcomes. PMID- 2211131 TI - Statistical quality control in nursing homes: assessment and management of chronic urinary incontinence. AB - This article describes a statistical quality control system that allows nurse managers to monitor staff performance of a critical patient care function. Descriptive data concerning patients' incontinence frequencies were collected during a two-day assessment period for 87 patients under conditions that guaranteed that the patients' protective garments were changed on a one- or two hour basis. The average and expected norms of patient wetness were calculated for a sample of patients in four different nursing homes. Periodic monitoring of patient wetness in each sample and the use of statistical quality control charts permitted nurse managers to determine if nursing aides were changing patients on either a one- or a two-hour schedule. The implications of the research for meeting federal incontinence care standards and for assuring high-quality patient care are discussed. PMID- 2211132 TI - Morbidity and medical care utilization of old and very old persons. AB - This report compares the morbidity, health care and drug utilization, and health status of random samples of HMO-enrolled Medicare beneficiaries ages 65-79, and 80 and over. The population represented 3,683 person-years of Kaiser Permanente eligibility (59.2 percent female). Those 80 and over were 20 percent of the person-years (64.1 percent female). The effects of age and sex on morbidity and utilization were analyzed using log linear models that controlled for eligibility, and using two-way analyses of variance of rates. Few differences were found in the morbidity experiences and utilization rates of the two age groups. Indicators of self-reported health status did differ. The findings support the idea that noninstitutionalized very old persons are the healthy survivors of their cohort. Their health care needs may not be much different than younger old persons in terms of the types and amounts of health care services needed. PMID- 2211133 TI - Not putting your money where your mouth is. PMID- 2211134 TI - NHS Act. Trusts threaten jobs and services. PMID- 2211135 TI - Birmingham. Child health clinics to close. PMID- 2211136 TI - Controversy surrounds new 'language line'. PMID- 2211137 TI - Smacking. Unacceptable limits. PMID- 2211138 TI - Identifying language impairment. PMID- 2211139 TI - Conductive education in Hungary and Britain. PMID- 2211140 TI - Continence in cerebral palsy. PMID- 2211141 TI - Education. Making your experience count. AB - The academic rigour and intensity of health visitor courses has always been acknowledged by health visitor lecturers and experienced by students but there has previously been little in the way of academic reward and recognition for their efforts. Now newly-validated health visitor courses are awarded the academic accreditation of diploma in professional studies in health visiting, if they take place in participating institutions using the credit accumulation and transfer scheme (CATS). PMID- 2211142 TI - Sleep problems: a group approach. AB - Reports on a successful approach to sleep disturbance jointly facilitated by clinical psychologists and health visitors. Where the clinical psychologist and health visitor were able to work closely together, it was shown that this increased knowledge of behaviour therapy techniques and enabled the health visitors to run future groups independently. Health visitors also reported feeling able to apply such techniques to other management problems in young children. PMID- 2211143 TI - Health visiting in a chest clinic. PMID- 2211144 TI - Fit for life in the mosque in South Tees. PMID- 2211145 TI - Public health workers from the start. PMID- 2211146 TI - Community charge. Help with paying the poll tax. PMID- 2211147 TI - What is happening in Camelford? PMID- 2211148 TI - Who lives, who dies, who decides? AB - The financial costs of the ethical dilemmas in the health care industry are profound, and the emotional ramifications for the patient and family are even more costly. As critical care nurses and as health care consumers, we must create an impetus for change. We need to ensure that we contribute to the quality of life while dealing with the conflicting values inherent in the right-to-die question. Together, we can create an ethical practice environment for ourselves, our families, and the patients for whom we care. PMID- 2211149 TI - Study of educational experiences, support, and job satisfaction among critical care nurse preceptors. AB - Experienced critical care staff nurses are frequently called to serve as clinical preceptors for nurses and nursing students who are unfamiliar with the critical care unit. These critical care nurse preceptors require educational preparation, continuing education, and support for their role. This descriptive correlational study surveyed 73 critical care nurse preceptors at 10 teaching hospitals in a metropolitan area in the Midwest. Forty-eight (65.8%) participants reported receiving some type of educational experience to prepare them for the role of preceptor. Only 24.7% of the respondents, however, participated in continuing education experiences related to the preceptor role. Job satisfaction was measured with a 48-item Likert scale developed for nurses by Slavitt et al. No significant differences in job satisfaction were reported for preceptors who received educational preparation and those who did not. However, the type of unit in which the preceptor worked did affect job satisfaction. Critical care preceptors in units classified as intermediate care and emergency departments had greater levels of job satisfaction than nurses working in intensive care units (t[68] = 2.52, p = 0.01). In addition, the longer the preceptor worked in critical care, the lower the level of job satisfaction (r = -0.210, p = 0.04). Job satisfaction was also influenced by the support preceptors received from their institution; a significant positive correlation was seen between this support and the level of job satisfaction. A description of the format and content of preparation programs for critical care preceptors was also provided as a result of this study. PMID- 2211150 TI - Energy conservation during skin-to-skin contact between premature infants and their mothers. AB - The effects of skin-to-skin contact on three indexes of energy expenditure: heart rate, activity level, and behavioral state, were examined in a pilot study. It was hypothesized that skin-to-skin contact, because of its soothing effects, would increase sleep, lower activity level, and reduce heart rate. Eight healthy preterm infants in a neonatal intensive care unit, who had reached 34 to 36 weeks gestation, experienced one session of skin-to-skin contact for an interfeeding interval. Observations were made once each minute using continuous videotape throughout three consecutive interfeeding intervals (before, during, and after skin-to-skin contact). Significant treatment effects were found by repeated measures analysis of variance for behavioral state and activity level; pair-wise comparisons showed that quiet sleep frequency was significantly increased and activity level reduced during skin-to-skin contact. Infants had longer durations of quiet sleep during skin-to-skin contact. The Pearson product-moment correlation between heart rate and behavioral state was robust and generally linear, supporting use of heart rate as a measure of energy expenditure in these subjects. The findings suggest that skin-to-skin contact is a simple, cost effective intervention that reduces activity and state-related energy expenditure. PMID- 2211151 TI - Nursing perception of the availability of the intensive care unit medical director for triage and conflict resolution. AB - The Joint Commission on the Accreditation of Healthcare Organizations and the Society of Critical Care Medicine call on the physician medical director of the intensive care unit (ICU) to play an important role in admission and discharge decision-making. To assess nursing perception of the medical director's involvement in this decision-making, we analyzed data from a questionnaire administered at an annual ICU management conference to ICU nursing supervisors representing 101 hospitals and 137 ICUs. We asked nurses if the medical director or his or her designee (excluding residents) was available at night for triage, admission decision-making, and conflict resolution. In 21% (29) of the ICUs, nurses perceived no medical director at all. In the 54 ICUs with full-time medical directors, nurses in approximately 30% of the units said that there was no nighttime availability of the medical director or designee. The data suggest that many ICUs lack physician leadership in ICU management and resource allocation. PMID- 2211152 TI - Changes in self-concept during pulmonary rehabilitation, Part 1. AB - The purpose of this two-part study was to describe changes in self-concept during and after a formal pulmonary rehabilitation program. A 20-item semantic meaning differential scale was administered to 37 patients with severe chronic obstructive pulmonary disease who were participating in a multidisciplinary pulmonary rehabilitation program. Patients were asked to evaluate their past, present, and future selves on program admission, on program discharge, and 2 to 6 months after home discharge. Mean total self-concept score for the present self significantly increased between program admission and home discharge 3 weeks later (mean change 31.32 +/- 22.04, p less than 0.0001). No significant declines in self-concept were found 2 to 6 months after home discharge (p = 0.39). Men showed a significantly higher change in total self-concept score than women during the 3-week program (p = 0.03). However, the men's change score dropped significantly after home discharge (p = 0.02), suggesting a need for more intensive follow-up care than with women. The self-concept tool in this study provided an easy way to monitor subjective changes in psychologic status. PMID- 2211154 TI - Recovery after cardiovascular events. Overview. PMID- 2211153 TI - Changes in self-concept during pulmonary rehabilitation, Part 2. AB - This two-part study describes changes in self-concept during pulmonary rehabilitation. A 20-item semantic meaning differential scale was administered to 37 patients with severe chronic obstructive pulmonary disease who were participating in a multidisciplinary pulmonary rehabilitation program. Patients were asked to evaluate their past, present, and future self-concepts on program admission, on program discharge, and 2 to 6 months after home discharge. In this part of the study item-level quantitative data as well as qualitative data from the counseling session at program discharge are reported. The quantitative data documented detailed changes in self-concept at various stages of pulmonary rehabilitation. Counseling session results indicated that patient involvement in item-level analysis greatly facilitates psychosocial intervention. Findings from this study establish clinical indications for use of the Self-concept Evaluation tool in adult patients with chronic obstructive pulmonary disease. Use of this tool is recommended early in the rehabilitation process. PMID- 2211155 TI - Differences in recovery from cardiac surgery: a profile of male and female patients. AB - The specific aim of this study is to compare and contrast the biophysical and psychosocial profile of men and women undergoing cardiac surgery (coronary artery bypass graft and valve replacement) during the perioperative and home recovery period. Coronary artery disease appears to be qualitatively worse in women than men although the prevalence in women does not approach that in men until the seventh decade. Valvular disorders also reveal a different profile by sex with the greater valvular problems in women related to the fact that women have more rheumatic heart disease. A prospective, longitudinal design with a convenience sample of 117 patients undergoing cardiac surgery and their spouses (234 subjects) from five Northern California hospitals was used to tap patient response at three critical perioperative data points. Female patients were observed during the perioperative period to have significantly more shortness of breath, poorer cardiac functional status (New York Heart Association), significantly longer intensive care unit stays, and proportionately more deaths. At 1 and 3 months after discharge, however, their recoveries did not differ significantly from men's when they were compared on sexuality, recreation, or return-to-work variables. Surprisingly, female patients had significantly less mood disturbances as measured by the Profile of Mood States than their male counterparts, and they scored higher on measures of family satisfaction than did male patients. Implications of the study involve early recognition of heart disease in women, preparation of families for longer intensive care unit stays, and appreciation of different psychosocial responses to surgery. PMID- 2211156 TI - Family recovery after vascular surgery. AB - Twenty-one families were observed in a 3-month study to assess family coping with major vascular surgery and recovery. Analysis of family measures data (the Family APGAR, the Family Inventory of Resource for Management, and the Family Crisis Oriented Personal Evaluation Scales) was combined with grounded theory method to assess family responses over time and recovery outcomes. Containment emerged as the major conceptual category of the grounded theory. Containment refers to a constellation of constructed meanings for events and behavioral responses used by families to regulate the impact of the surgical crisis and reduce family disruption. This "contained" coping pattern was manifested in families' avoidant behaviors and narrow definitions of the problem: that is, they defined their situation in terms of the surgical repair as cure rather than palliative intervention for a chronic, progressive disease. Situational factors such as the insidious development of the illness and the primary focus of care providers in the hospital on surgical care (allowing families' narrow definitions of their situation to remain unchallenged) also contributed to containment. Containment resulted in poor risk factor management as a major recovery outcome. Isolation and family conflict were evident throughout the recovery period. Concerns generated by continued evidence of morbidity during recovery contributed to a developing awareness of underlying disease, and diminishing containment when this growing awareness was openly shared within the family. Significant findings of the family measures analysis were compared with the grounded theory of the qualitative data. Each corroborated the other in key dimensions. PMID- 2211158 TI - Torsade de pointes: a critical care nurse's dilemma. AB - Torsade de pointes is a polymorphous ventricular tachycardia characterized by a gradual change in the direction of the QRS complex. Because critical care nurses are the first to recognize arrhythmias, they require the knowledge and skill to intervene appropriately. This case report focuses on identification of the characteristics, contributing factors, therapeutic modalities, and relevant nursing diagnoses for the patient with torsade de pointes. PMID- 2211157 TI - Nurse-monitored cardiac recovery: a description of the first 8 weeks. AB - Health problems and related patient management during early recovery after cardiac surgery are not well documented. As part of a larger study of recovery from cardiac surgery 75 patient-care giver pairs received telephone calls from nurses at 1, 2, 3, 4, 6, and 8 weeks after discharge for the purpose of intervening to facilitate early recovery at home. After each call, nurses recorded detailed notes on the patients' progress and concerns. Content analysis of detailed nurses' recordings revealed the following predominant nursing actions: assessment, provision of support, reinforcement of predischarge teaching, referrals, and teaching. The five nursing diagnoses that occurred most frequently across the 8-week recovery period were altered comfort: pain; ineffective coping, individual; activity intolerance; sleep pattern disturbance; and altered nutrition. In response to these problems, patients managed and prevented health-related problems and engaged in health promotional and normalizing activities. By anticipating common problems in recovery, patients and care givers can be better prepared for going home. Similarly nurses can be better prepared to anticipate and respond to common recovery problems. PMID- 2211159 TI - Role of angiotensin-converting enzyme inhibitors in congestive heart failure. AB - Conventional therapy for congestive heart failure (CHF) includes sodium restricted diet, diuretics, digitalis, vasodilators, and short-term intravenous administration of beta-adrenergic agonists during episodes of decompensation. A specific class of vasodilators, the angiotensin-converting enzyme inhibitors, has recently gained predominance in the treatment of congestive heart failure. The primary mechanism of action is to reduce production of angiotensin II by competitive inhibition of the enzyme that converts angiotensin I into angiotensin II. Reduced levels of angiotensin II, in turn, promote vasodilation and lower aldosterone production. The benefits of angiotensin-converting enzyme inhibitor therapy in chronic congestive heart failure have been demonstrated by improvement in left ventricular performance, exercise capacity, functional status (using New York Heart Association classification), and survival. PMID- 2211160 TI - Mechanical cardiopulmonary support for refractory cardiogenic shock. AB - From February 1982 to February 1990, 38 patients (30 male patients and 8 female patients) ranging in age from 10 to 78 years (mean 49.4 years) have been supported with arteriovenous extracorporeal membrane oxygenation (ECMO) at St. Louis University Medical Center as a resuscitative system for cardiac arrest or cardiogenic shock. All patients were unresponsive to conventional resuscitative measures including an intraaortic balloon pump in 25 patients. Patients were resuscitated in the intensive care unit, cardiac catheterization laboratory, or the emergency department. Diagnosis varied from acute myocardial infarctions (12 patients), ischemic disease (15 patients), end-stage cardiomyopathy (7 patients), congenital heart disease (3 patients), or postoperative cardiac transplant graft rejection (1 patient). Three patients could not be resuscitated with ECMO because of low flow, but the remaining 35 (92%) achieved hemodynamic stability with ECMO flows greater than 2 L/min/m2. Duration of support ranged from 0.5 to 130 hours (mean 28 hours). Twenty-four patients were successfully weaned from ECMO support after coronary artery bypass (five patients), cardiac transplantation (two patients), or ventricular assist device insertion (eight patients), or with inotropic support (nine patients). Of the 14 patients not weaned, three were inadequately resuscitated, two had percutaneous transluminal coronary angioplasty while receiving ECMO, and nine were not candidates for further intervention. Nine (24%) patients were discharged and are long-term survivors. Our results indicate that resuscitative ECMO is useful for intervals of 12 to 24 hours and can best be applied with (1) patients younger than 60 years of age; (2) patients having acute events (failed percutaneous transluminal coronary angioplasty) amenable to surgical intervention; and (3) candidates for cardiac transplantation who could be switched to more sophisticated devices within 12 to 24 hours of ECMO insertion. With these criteria, ECMO, when used as a resuscitative system, can result in increased survival in selected patients with refractory cardiogenic shock or cardiac arrest. PMID- 2211161 TI - Pain experiences of intensive care unit patients. AB - The purpose of this study was to describe various dimensions of the pain experiences of intensive care unit (ICU) patients. A purposive, primarily surgical sample of 24 ICU patients from two hospitals was interviewed after transfer from ICU. All but one patient remembered their ICU stay. Although this and six other patients had no recall of pain, 63% of the sample rated their pain as being moderate to severe in intensity. In a subgroup of nine patients having cardiac surgery, mean morphine sulfate administration during the first three postoperative days was 14 mg/day. This group of patients reported a lack of total pain relief from analgesics. Patients also described various sources of their pain, difficulties they had in communicating their pain, and nonpharmacologic methods that helped relieve their pain. Results of this study clearly indicate that not only pain but its communication and treatment were significant problems for a substantial portion of this ICU sample. Further descriptive and experimental research of pain characteristics and treatment practices for ICU patients is urgently needed. Improvements in nursing practice that result from such research may make a substantial difference in the comfort and well-being of critically ill patients. PMID- 2211162 TI - Fungal pseudomeningitis superimposed on Escherichia coli meningitis. AB - Pseudomeningitis is the demonstration of microorganisms from the cerebrospinal fluid by stain or culture in a patient with symptoms suggesting meningitis. This is a report of fungal pseudomeningitis superimposed on a case of nosocomial Escherichia coli meningitis resulting from a neurosurgical procedure. Critical care personnel need to be aware of the possibility of pseudomeningitis with or without associated meningitis in the appropriate setting. PMID- 2211163 TI - Evaluating sources for secondary analysis. AB - Secondary analysis can be extremely versatile in understanding change of phenomena and extending previous studies. However, all data are not created equal. When using secondary sources, it is important to evaluate the data, weigh potential biases, and adopt an attitude of healthy skepticism. Although the potentials of secondary analysis are enormous, certain problems can be avoided if sources are evaluated carefully. Nurse researchers should be aware of some limitations of secondary data sets. Expert knowledge of research designs and statistical techniques, in addition to an open and creative mind, will be invaluable assets in answering the preceding eight questions. PMID- 2211164 TI - Ethical issues in critical care. Real presence. PMID- 2211165 TI - The physiologic basis for continuous mixed venous oxygen saturation monitoring. AB - Critically ill patients often have conditions that reduce oxygen delivery and increase oxygen demand. Routine nursing care, such as suctioning, positioning, and bathing, also increases the patient's oxygen demand. If the patient's oxygen demand exceeds the supply, dysrhythmias, hypotension, altered level of consciousness, and other adverse responses can occur. We describe use of continuous monitoring of mixed venous oxygen saturation (SvO2) as a tool to assess the patient's supply/demand balance during nursing care. The physiology of oxygen transport is reviewed, and oxygen delivery, reserve, and consumption are defined. Conditions that decrease oxygen delivery and increase oxygen demand are discussed, and the effects on SvO2 are illustrated. With continuous SvO2 monitoring, critical care nurses can see the effect of their nursing care on the patient's oxygenation and can adjust their care according to the patient's tolerance. PMID- 2211167 TI - Effects of a lateral turn on mixed venous oxygen saturation and heart rate in critically ill adults. AB - The purpose of this study was to determine the effects of a lateral turn on mixed venous oxygen saturation (SvO2) and heart rate in 183 critically ill adults. Mean SvO2 decreased from a baseline of 67% to 61% saturation (p less than 0.0001) immediately after turning and gradually returned to 66% saturation (p less than 0.002) within 4 minutes. Mean heart rate increased slightly from a baseline of 99 beats/min to 102 beats/min (p less than 0.0001) immediately after turning and decreased slightly to 101 beats/min (p less than 0.0004) within 4 minutes. These statistically significant changes in SvO2 and heart rate were not clinically significant for most patients. However, physiologic responses to turning were highly variable. SvO2 reductions of 25% or more from baseline, heart rate increases and decreases of 10 beats/min or more, and signs of activity intolerance occurred in some patients. Nurses should expect critically ill patients to have a decrease in SvO2 of approximately 9% of baseline and small changes in heart rate after turning. These changes should be transient, with SvO2 and heart rate gradually returning toward baseline levels during the next 4 minutes. If turning triggers large or prolonged changes in SvO2 or heart rate, prompt repositioning and evaluation are needed to prevent adverse effects. PMID- 2211166 TI - Effects of endotracheal suctioning on mixed venous oxygen saturation and heart rate in critically ill adults. AB - The purpose of this multisite study was to determine the effects of endotracheal suctioning on mixed venous oxygen saturation (SvO2) and heart rate in 189 critically ill adults. One-pass, intermittent suction was applied for 10 or fewer seconds, with three prehyperoxygenation and three posthyperoxygenation breaths of 100% oxygen. Subjects at three hospitals (n = 127) underwent suctioning using hyperoxygenation with anesthesia bags and traditional suction catheters (open suction method). Subjects at one hospital (n = 62) underwent suctioning with hyperoxygenation by ventilator and in-line suction catheters (closed suction method). For subjects from all hospital sites combined, the SvO2 decreased from 67% to 64% (p = 0.001), a 4% change from baseline, and returned to baseline within 2 minutes. However, in subjects receiving the open method of suction, SvO2 dropped from 66% to 62% immediately after suctioning and returned to baseline within 4 minutes. In contrast, when the closed suction method was used, SvO2 rose from 67.7% to 67.86% immediately after suctioning, drifting upward to 71% for the next 2 minutes before dropping toward the baseline after 4 minutes. Mean heart rate increased from a baseline of 99 beats/min to 104 beats/min immediately after suctioning (p = 0.001), a 5% change from baseline, and gradually returned to baseline over the next 4 minutes. No significant differences were seen in heart rate between subjects having the open versus closed suction method. In conclusion, the closed suction method showed a higher SvO2 after endotracheal suctioning compared with the open suction method (p = 0.0001). Some form of hyperoxygenation before and after endotracheal suctioning is recommended. PMID- 2211168 TI - Effects of a 1-minute back rub on mixed venous oxygen saturation and heart rate in critically ill patients. AB - In this study we evaluated mixed venous oxygen saturation (SvO2) and heart rate responses after a 1-minute back rub in 173 critically ill patients. The back rub was the third and last intervention in a study conducted in intensive care units at four hospitals. For this multiple-intervention study all patients were placed in a supine position to obtain baseline SvO2 and heart rate, then underwent suctioning via endotracheal tube, and were turned to a lateral position. After 15 minutes in a side-lying position, the subjects received a 1-minute back rub. Data were collected immediately after the back rub and at 1-minute intervals for 4 minutes. After the back rub, SvO2 decreased immediately from the mean baseline of 67% to 63% and gradually increased, returning to baseline by minute 4. The mean baseline heart rate of 99 beats/min increased to 103 beats/min immediately after the back rub and gradually decreased after massage, but remained higher than baseline by minute 4. Although the findings were statistically significant (p = 0.0001), these minimal physiologic changes do not represent clinical significance. Based on the findings, the back rub, a traditional nursing measure that can provide comforting touch, represented a minor stimulus affecting heart rate and oxygen demands in most critically ill patients. However, because of the variability found in heart rate and SvO2, individual responses need to be assessed. PMID- 2211169 TI - Evaluating oxygen delivery and oxygen utilization with mixed venous oxygen saturation monitoring: a case study approach. AB - Three cases studies are presented to demonstrate clinical application of mixed venous oxygen saturation (SvO2) monitoring in critical care nursing practice. Examples of critically ill patients are used to demonstrate how SvO2 monitoring can be used in clinical practice to reflect an imbalance between oxygen delivery and oxygen utilization. In the first case, the patient had a problem with oxygen delivery. Continuous SvO2 data aided nurses in guiding, adjusting, and assessing therapy. The second case demonstrates how SvO2 monitoring can provide an early sign of a life-threatening complication. The final case is one in which the patient had a problem with oxygen utilization. In all the cases, continuous SvO2 data provided important information about the balance between oxygen delivery and oxygen utilization. PMID- 2211170 TI - Evaluation of the patient having cardiac surgery in the postoperative rewarming period. AB - Ensuring adequate oxygen delivery to the tissues with respect to oxygen demand is the treatment goal in patients undergoing coronary artery surgery (CAS). In this study we examined changes in temperature, arterial oxygen saturation (SaO2), cardiac index (CI), oxygen consumption (VO2), and mixed venous oxygen saturation (SvO2) over the initial 4-hour rewarming period in 36 patients having CAS. When patients were admitted to the intensive care unit the mean temperature was 36.27 degrees C, and it increased to 37.50 degrees C; SaO2 was 97.67% at the beginning and end of the 4-hour period; CI was 2.88 L/min/m2 and rose to 3.00 L/min/m2; VO2 was high at 0.320 L/min on admission and remained high at 0.290 L/min at the end of the 4-hour rewarming period; and SvO2 was 70.83% initially and declined to 66.53% in the same period of time. Continuous SvO2 monitoring was valuable in the ongoing assessment and management of the patients in stable, mildly hypothermic condition after CAS during the 4-hour postoperative rewarming period. PMID- 2211172 TI - Perspectives on the interpretation of continuous mixed venous oxygen saturation. AB - Continuous measurement of mixed venous oxygen saturation (SvO2) is a beneficial method for evaluating overall dynamic tissue oxygen balance in critically ill patients. Several important factors, however, may influence the accurate analysis of SvO2 data trends. In this review we highlight these factors and support cautious interpretation of SvO2 in conjunction with other available patient data and with strict attention to the clinical value and limitations of the parameter. PMID- 2211171 TI - Effects of position changes on mixed venous oxygen saturation in patients after coronary revascularization. AB - The purpose of this study was to investigate the effects of position changes on mixed venous oxygen saturation (SvO2) and to describe the mechanisms responsible for SvO2 changes reported to occur with position changes. The study was done from 4 to 8 hours after surgery in 34 patients after coronary artery bypass grafting. Subjects were put through a series of six position changes, including head of bed elevations and right and left lateral decubitus with return to supine between each. Each position was maintained for 30 minutes. SvO2, arterial oxygen saturation (SaO2), and oxygen consumption (VO2) were measured before and after each position change. Overall mean subject data demonstrated a decrease in SvO2 with each of the lateral position changes. The SvO2 did not drop below 60% in these mean data, and this drop returned to baseline by 5 minutes. There were no significant changes in the mean data for VO2 or SaO2. No significant correlation was found in the mean data between SvO2 and VO2 or SvO2 and SaO2 measurements. Trends were demonstrated in five specific cases that suggested a correlation between changes in SvO2 and changes in VO2 and SaO2. In conclusion, this study demonstrated that subjects were able to tolerate position changes with no clinically significant changes in SvO2, SaO2, or VO2. PMID- 2211173 TI - Argon beam coagulation systems. AB - We evaluated the two argon-enhanced coagulation (AEC) systems currently on the market from two different manufacturers, basing our ratings primarily on performance and safety and considering the clinical perspectives gained from discussions with surgeons who use these units. We rated both units Acceptable. Because one unit has characteristics that provide a potential safety advantage (i.e., it produces lower gas pressure at the tissue and limits certain gas flow/power combinations), we ranked it slightly higher than the other unit. However, sufficient laboratory and clinical studies must still be carried out to assess the risk of gas embolism with these and future systems. PMID- 2211175 TI - Signal-averaging ECGs: an update. AB - ECRI has recently received many inquiries about ECG signal averaging and its clinical applications. The following report examines the current applications and state of development of this rapidly evolving technology. PMID- 2211174 TI - Rechargeable lead-acid batteries. AB - Batteries used in medical equipment, like their counterparts in consumer products, attract little attention until they fail to function effectively. In some applications, such as in emergency medical devices, battery failure can have fatal consequences. While modern batteries are usually quite reliable, ECRI has received 53 written problem reports and countless verbal reports or questions related to battery problems in hospitals during the past five years. This large number of reports is due, at least in part, to the enormous quality of batteries used to operate or provide backup power in contemporary hospital equipment. As part of an ongoing evaluation of rehabilitation assistive equipment, ECRI has been studying the performance of 12 V rechargeable deep-cycle lead-acid batteries used in powered wheelchairs. During the course of this evaluation, it has become apparent that many professionals, both clinical and industrial, regard batteries as "black box" devices and know little about proper care and maintenance--and even less about battery selection and purchase. Because equipment performance and reliability can be strongly influenced by different battery models, an understanding of battery characteristics and how they affect performance is essential when selecting and purchasing batteries. The types of rechargeable batteries used most commonly in hospitals are lead-acid and nickel-cadmium (nicad), which we compare below; however, the guidance we provide in this article focuses on lead-acid batteries. While the examples given are for high-capacity 12 V deep-cycle batteries, similar analyses can be applied to smaller lead-acid batteries of different voltages. PMID- 2211177 TI - Perma Power power strips. PMID- 2211176 TI - Mismating of precision brand medical gas fittings. PMID- 2211178 TI - Linkage disequilibrium in laboratory strains of Drosophila ananassae is due to drift. AB - Two inversions in the opposite arms of the third chromosome are common in natural populations of Drosophila ananassae. When the strains are taken to laboratory, these inversions have been found to persist for several generations. Four natural populations were sampled and the data on the combinations between 3L and 3R karyotypes were obtained. For all the four populations, laboratory stocks (mass culture and isofemale lines) were established and maintained in food bottles by transferring fifty flies in each generation. After ten generations, chromosomes of all stocks were sampled. The results show that the two linked inversions are associated randomly in natural populations and in laboratory stocks established from mass culture. On the other hand, the same two inversions show non-random association (linkage disequilibrium) in several isofemale lines. The random association between inversions in natural and mass culture laboratory populations as contrasted to laboratory populations established from single females suggest that random drift is the cause of non-random association in isofemale lines. The tight linkage between the two inversions as evidenced by the results of recombination studies reported earlier, supports the notion that linkage disequilibrium is caused by drift. PMID- 2211180 TI - C-band fusion and behaviour of the involved chromosomes during meiotic prophase I of the male domestic pig. AB - Behaviour of acrocentric chromosome synaptonemal complexes (SCs) and constitutive heterochromatin (C-band) during meiotic prophase I of the male domestic pig was studied using surface spreading and silver staining techniques. At late zygotene C-band regions of complete or incomplete SCs of the acrocentric chromosomes are represented by enlarged structures. At the same time these structures commenced fusion, which is accomplished at pachytene. Using kinetochores and NORs as markers, the pachytene metacentric, acrocentric, and nucleolar SCs can be distinguished. In 96.7% of the pachytene nuclei, either all or some of the acrocentric SCs are associated at their centromeric regions, forming one or two large globular or shapeless masses that represent chromocenters. The SCs are assorted at random in all types of association except in single association of all the SCs. Order of associated SCs varies from one association to another. The C-band region of SC, the portion inside the chromocenter core, is differentiated as thicker and darker structures from the chromocenter mass. A silver-positive core-like structure in meiotic chromosome C-bands, probably a vector for meiotic C-band ectopic pairing, provides faithful representations of C-band behaviour during meiosis. PMID- 2211179 TI - The high resolution G- and R-banding pattern in chromosomes of river buffalo (Bubalus bubalis L.). AB - High resolution G- and R-banding patterns in chromosomes of river buffalo (Bubalus bubalis L.) were obtained by using early (G-bands) and late (R-bands) BrdU-incorporation in synchronized cell cultures. To better characterize the river buffalo chromosomes, GTG-, GBG-, and RBG-techniques were used. The total number of bands achieved were 490 (207 G-positive, 207 R-positive, 45 variable, and 31 centromeric regions). Only one common G- and R-banding nomenclature was reported. The number, position and intensity of G bands were highly similar by the structural GTG and the replicating GBG-techniques. However, the replicating G and R-bands appeared to be more distinct and reproducible than the structural G bands. Some changes in chromosome nomenclature (chromosomes 1p, 2p, 5p, and 21) were made when referred to the cattle homologues. PMID- 2211181 TI - Genetic load in northern populations of Drosophila subobscura. AB - O-chromosomes were sampled from two natural populations in Finland, one population in Sweden and one population from Spain. Viability was assessed using the Va/Ba balanced lethal strain. The genetic load for lethals and semilethals was 0.165/0.065 in Helsinki and 0.151/0.101 in Tvarminne, Finland; 0.309/0.118 in Gavle, Sweden and 0.351/0.112 in Barcelona, Spain. With the exception of the Gavle population, the results confirm the general picture that marginal populations are characterized by light loads in comparison with the central ones. Homozygotes for normal or almost normal chromosomes from the Gavle population were less viable than corresponding homozygotes from other marginal populations. Random combinations of wild chromosomes from the Spanish and Finnish populations did not show increased viability over random Spanish heterozygotes. PMID- 2211182 TI - Divergence in emergence time of host races due to differential gene flow. AB - Differential gene flow between adjacent plant populations, induced by environmental influences on reproductive characters such as flowering time, may increase isolation between them (Stam, 1983). With the aid of a simulation model, an analogous process is demonstrated for populations of phytophagous insects. Allochronic isolation due to differences in host plant phenology can be accentuated in sympatry. Interpretations of divergence between host-associated insect populations should take account of the potential effects of differential gene flow before invoking explanations involving selection. PMID- 2211183 TI - 'Trouble-shooting' microwave accelerated procedures in histology and histochemistry: understanding and dealing with artefacts, errors and hazards. AB - Heating by microwave irradiation (microwaving) is a controllable way to accelerate most processes of diffusion and many chemical reactions occurring in histoprocessing and histochemistry. Consequently, microwaving can be particularly time-saving. However, apart from desirable accelerations, unwanted diffusions and reactions may also occur. These can generate artefacts such as extraction of tissue components, chemical alterations of cellular content, and decomposition of thermally labile staining reagents. Artefacts may arise at all stages of histoprocessing, from fixation, through embedding, to staining. Whereas all artefacts result from heating, some specifically involve microwave ovens; e.g. irregular heating due to inhomogeneities in the microwave field, and ageing of the magnetron. Microwaving can involve certain hazards. Most of them also arise in conventional ovens, but a few are unique to microwave ovens; for example, aqueous contents heating faster than glass containers, and sparking due to labels written in pencil. The 'trouble-shooting' of microwave procedures requires an understanding of the nature of the heating process and of the procedure in question. In order to achieve this, the development and application of 'trouble shooting' charts for commonly used procedures is both recommended and illustrated. PMID- 2211184 TI - Physics of microwave technology in histochemistry. AB - Microwave technology has become important in preparatory techniques for microscopy in many different ways. This paper discusses various aspects of the physics of microwaves. It gives some theoretical background to understand the practical procedures. Some peculiarities in the optics of microwaves are pointed out, and the practical implications in particular of choosing the size and shape of samples and containers are discussed. Diffusion rates and chemical-reaction rates increase exponentially with temperature, so that precise temperature control is essential in most histochemical procedures. Such control is complicated by localized heating of the system, and of temperature sensors themselves, which may occur as a result of microwave irradiation. PMID- 2211185 TI - The American Society for Histocompatibility and Immunogenetics. 16th annual meeting. November 3-7, 1990, Century City, California. Abstracts. PMID- 2211186 TI - Nomenclature of platelet-specific antigens. PMID- 2211187 TI - Induction of erythrocyte HLA expression during interferon treatment and HIV infection. AB - Although HLA antigens are present on the surface membrane of most cells, erythrocytes express little or no HLA. Occasionally red cells from normal individuals or patients with certain diseases express elevated levels of these molecules. The reasons for such variations are currently not understood. We report here that the expression of very high levels of HLA on erythrocytes occurs in response to interferon alpha given as a therapeutic agent for viral hepatitis. Increased expression became apparent after the second or third week of treatment, peaked at 3-4 months, and decreased at the end of the treatment period. This chronology suggests that elevated HLA expression is originated during erythropoiesis and persists throughout the lifetime of the erythrocyte. Furthermore, erythrocyte HLA expression did not correlate with changes of plasma HLA or beta 2-microglobulin concentrations and was not affected by in vitro chloroquine treatment, ruling out the possibility that HLA was adsorbed from plasma. Increased expression of HLA on erythrocytes was also demonstrated in patients infected with the human immunodeficiency virus, a disease in which increased production of endogenous interferon has been previously documented. We conclude that high HLA expression in red cells occurs in response to persistent interferon stimulation. Further studies will determine if this effect can also be produced by interferon tau or other factors. PMID- 2211188 TI - Functional analysis of MHC class II-restricted T cells derived from a Caucasian with a DR4, Dw15, DQw8 haplotype. AB - Rabies virus-specific CD4+ T lymphocyte clones were isolated from a Caucasian male vaccine recipient (DR4/7, DQw2/w8; DPw4) and studied for their major histocompatibility complex restricting elements. None of the rabies-specific T cell clones could be induced to proliferate to antigen by either lymphoblastoid cells or DR-transfected L cells expressing DR4 molecules of the Dw subtypes commonly found on Caucasian individuals (Dw4, Dw10, Dw13, Dw14). The HLA-Dw subtype of the rabies vaccine recipient was determined by conventional mixed lymphocyte culture, and the results revealed that this individual had a DR4 (Dw15), DR7 (Dw7) phenotype. The presence of the DR4, Dw15 antigen was confirmed by nucleotide sequencing of the DR4B1 gene corresponding to the DRB1*0405 allele. Significant antigen-induced T-cell proliferative responses were obtained with two DR4, Dw15, DQw4 homozygous lymphoblastoid cell lines of Japanese origin (HAS-15 and KT-3) and with a L-cell transfectant expressing the DR4, Dw15 molecule. The existence of the DR4, Dw15 antigen in the Japanese has been reported to be associated with the DQw4 specificity. However, the presence of DQw8 (previously designated DQw3.2) and the absence of DQw4 in the lymphoblastoid cells of the Caucasian rabies vaccine was confirmed with monoclonal antibodies IVD12 (anti DQw7 + DQw8 + DQw9) and HU46 (anti-DQw4) and by the reactivity of a DQw8 restricted antigen-specific T-cell clone. These studies indicate, contrary to previous findings, that the DR4, Dw15 molecule may be present in Caucasian (non Japanese) individuals in association with DQw8. PMID- 2211189 TI - Cytotoxic and proliferative T-cell clones with antidonor reactivity from a patient transplanted for severe combined immunodeficiency disease. AB - Patients who have become split lymphoid chimeras (T cells of donor origin, B cells and monocytes of host origin) following transplantation of HLA haploidentical marrow for the treatment of severe combined immunodeficiency disease provide a unique model for the study of tolerance. One such patient, UPN 345, was transplanted with maternal marrow and was found to have antidonor proliferative reactivity without detectable donor-directed cytotoxicity when tested at 18, 23, and 66 mos following bone marrow transplantation. In bulk culture, the proliferation to donor cells could be blocked by monoclonal antibodies to HLA-DR and -DQ. Nine clones with antidonor reactivity were established by limiting dilution techniques from a mixed lymphocyte culture between engrafted T cells and irradiated donor E rosette-negative cells. All of the clones were of maternal donor origin, and all were CD3+CD4+CD8-. The clones were tested for proliferative and cytotoxic activity toward donor, host, and paternal B-lymphoblastoid cell lines (B-LCL). Six clones proliferated strongly to maternal B-LCL but not to host B-LCL. Six clones were found to exclusively lyse maternal B-LCL. Four of the clones had both antidonor cytotoxic and antidonor proliferative reactivity. Monoclonal antibody blocking studies were performed on five of the six clones with cytotoxic activity. The antidonor cytotoxicity was not inhibited by monoclonal antibodies to class I determinants; however, three clones were inhibited in the presence of monoclonal antibody to DR, one clone was inhibited by anti-DQ monoclonal antibody, and one clone was inhibited by anti-DP monoclonal antibody. The cytotoxicity of all five clones was inhibited by monoclonal antibody to CD4. These data indicate that antidonor reactivity may also include a cytotoxic component which is not apparent in bulk cultures and which, based on our limiting dilution studies, is probably controlled by regulatory cells. Both the antidonor cytotoxicity and the antidonor proliferation appear to be directed primarily toward donor HLA class II antigens that are not shared with the patient. PMID- 2211190 TI - HLA and Kaposi's sarcoma in solid organ transplantation. AB - Of 188 cases of Kaposi's sarcoma arising de novo after transplantation, HLA-A, -B typing was available for 135 and HLA-DR typing available for 67. Compared to the reported HLA phenotype frequencies of renal transplant recipients in the Southeast Organ Procurement Foundation (SEOPF), there is a significantly decreased frequency of HLA-A1 and HLA-B7, and increased frequency of HLA-B5, -B8, -B18, and -DR5. The most striking characteristic of the Kaposi's sarcoma group was its ethnic background. Fifty-six percent of patients were Italian, Greek, Jewish, or Arabic. When this ethnic background is considered, the expected HLA phenotype frequencies are almost exactly the same as in the Kaposi's sarcoma population. The quality of donor-recipient HLA match was evaluable for 106 patients. Only 22% had four or more mismatches, and 59% had at least two antigens matched. This argues against poor donor-recipient matching as a risk factor for developing Kaposi's sarcoma after transplantation. PMID- 2211191 TI - Allopathic residencies: current and former residents' viewpoints. PMID- 2211192 TI - Commenting on L-tryptophan and osteopathic physicians in allopathic residencies. PMID- 2211193 TI - Need for documenting OMT. PMID- 2211194 TI - Calling for theories that test the underlying osteopathic concepts. PMID- 2211195 TI - Nociceptive reflexes and the somatic dysfunction: a model. AB - A model of somatic dysfunction is developed in which restriction in mobility and autonomic, visceral, and immunologic changes are produced by pain-related sensory neurons and their reflexes. Nociceptors are known to produce muscular guarding reactions, as well as autonomic activation, when musculoskeletal or visceral tissue is stressed or damaged. This guarding causes abnormal musculoskeletal position and range of motion. Local inflammatory responses and autonomic reflexes further reinforce nociceptor activity, maintaining restriction. Nociceptive autonomic reflexes also evoke changes in visceral and immunologic function. Finally, maintenance of muscles, joints, and related tissues in an abnormal guarding position causes changes in the connective tissues, solidifying the abnormal position. Stretching these tissues into a normal range of motion will restimulate the nociceptor, reflexly reinforcing the somatic dysfunction. This model has evolved from Korr's neurologic model but emphasizes the nociceptor and its reflexes as a source of the connective tissue, circulatory, visceral, and immunologic changes seen in the somatic dysfunction. PMID- 2211196 TI - Thoracic outlet syndrome--a myofascial variant: Part 2. Treatment. AB - Thoracic outlet syndrome (TOS) may be treated successfully with a powerful form of myofascial release manipulation and stretching. Self-stretching exercises complement all other treatment modalities for TOS. Maximal effect is achieved with high-frequency, progressive stretching, tapered rapidly to a maintenance level as symptoms diminish. Stretching must be demonstrated "hands on" with the patient and reviewed and modified regularly. The techniques are similar to those of Travell and Simons, with modifications. The pain of TOS is intimately connected with short, contracted muscles that develop trigger points. An engram for the shortened muscles develops centrally. The myofascial release technique involves local release of myofascial structures, re-energizing of the tissues, and reprogramming of the central engram for the particular muscle length. PMID- 2211197 TI - Osteopathic medicine: the profession's role in society. PMID- 2211199 TI - Preoperative or postoperative brachytherapy for patients with endometrial carcinoma stage I and II. AB - In endometrial carcinoma, vaginal vault brachytherapy is performed to improve the local control rate and to decrease vaginal recurrences. To assess the best chronology of this brachytherapy compared to surgery, we have retrospectively analyzed results of treatment of patients treated either with preoperative brachytherapy (60 Gy) and then radical hysterectomy with bilateral salpingo oophorectomy (RH-BSO) (Group 1), or with RH-BSO and then postoperative brachytherapy (60 Gy) (Group 2). There were one hundred twenty-one patients in Group 1 and 63 in Group 2. The mean age was 61.8 years in Group 1 and 64.3 in Group 2. In Group 1, 73% of the patients were Stage I, and 77.6% were in Group 2. The two groups were comparable for histological grading and depth of tumoral invasion into the myometrium. Brachytherapy was delivered with one uterine and two vaginal sources in Group 1 and with three vaginal sources in Group 2. Doses to the reference volume and to reference points were calculated according to ICRU recommendations. Brachytherapy data were similar in the two groups except reference volume, which was smaller in Group 2. Local control rate was 87% in Group 1 and 91% in Group 2. Distant metastasis occurred in 12% of patients in Group 1 and 9% in Group 2. The 5-year actuarial survival rate was 84% in Group 1 and 89% in Group 2. Regarding stage, histological grading, and depth of tumoral invasion, no differences were observed between the two therapeutic groups. The only prognostic factor in the entire population was Stage. The 5-year actuarial survival rate was 91% for Stage I patients and 69% for Stage II (p value less than 0.03). The late severe complication rate was 14% in Group 1 and 7.9% in Group 2, a difference which was not statistically significant. We concluded that since no differences were observed between the two techniques, vaginal brachytherapy should be performed postoperatively when surgery is the first treatment (Stage I or II, grade 1 or 2, and no deep tumoral invasion into the myometrium). PMID- 2211198 TI - Prophylactic irradiation of the para-aortic lymph node chain in stage IIB and bulky stage IB carcinoma of the cervix, initial treatment results of RTOG 7920. AB - From November 1979 to October 1986, 367 patients were entered onto RTOG 7920 and randomized to receive either pelvic irradiation alone or pelvic plus para-aortic radiation. Patients with Stage IIB cervical carcinoma who had not undergone curative surgery and patients with Stages IB and IIA cervical carcinoma who were determined by digital exam to have primary tumors measuring 4 cm or greater in lateral dimension were eligible for this study. Clinically apparent or surgically involved para-aortic nodes were reason for exclusion from the study. Pelvic irradiation consisted of 1.6-1.8 Gy per day for 5 days per week to a total of 40 50 Gy. Para-aortic irradiation delivered 44 to 45 Gy in 1.6-1.8 Gy per day, 5 days per week. Pelvic irradiation was to be completed in 4 1/2 to 6 1/2 weeks and para-aortic irradiation in 4 1/2 to 5 1/2 weeks. Intracavitary brachytherapy delivered a total of 4000-5000 mg hr of radium-equivalents or 30-40 Gy to point A. Patients were stratified prior to random treatment assignment by histology, para-aortic nodal status (negative vs. unevaluated), and FIGO stage. As of June 1, 1989, 30 cases were excluded, including five patients who were inevaluable. Two patients who refused the assigned treatment were also excluded. Therefore, a total of 330 cases were analyzable. At 5 years the estimates of survival, the primary endpoint, for the pelvic only and pelvic plus para-aortic irradiation arms are 55% and 65%, respectively (p = 0.043). Several secondary endpoints were also analyzed. Estimates for loco-regional control at 5 years are, for pelvic irradiation only, 66%, and for pelvic plus para-aortic irradiation, 75% (p = 0.21). Distant metastases are estimated in 32% of pelvic irradiation only patients and 25% of pelvic plus para-aortic irradiation patients at 5 years (p = 0.17). When the first disease failure patterns are examined, more patients fail distally when treated only with pelvic radiation than when using pelvic plus para aortic fields (p = .04). In analysis of patients with grade 3 (severe), grade 4 (life-threatening), and grade 5 (fatal complications), 8% of the patients in both groups had grade 3 severe complications. In the pelvic plus para-aortic group, 11 patients had grade 4 and 2 had grade 5 complications, whereas 6 had grade 4 and none had grade 5 in the pelvic only treatment group.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2211200 TI - Patterns of failure in patients with stage I, grade 3 carcinoma of the endometrium. AB - Patients with high grade, early stage endometrial carcinoma are reported to have worse survival and local control rates than those with low grade carcinomas. To define failure patterns further in patients with FIGO Stage I, grade 3 endometrial carcinomas, the patients from three institutions who received adjuvant or definitive radiation (RT) were analyzed. Of 119 patients meeting the criteria of Stage I, grade 3 endometrial carcinoma, 57 patients received preoperative radiation, 49 patients received postoperative radiation, and 10 patients received definitive radiation with 5-year actuarial survival rates of 64%, 73%, and 65%, respectively. Three additional patients received both preoperative and postoperative treatment. The overall local control rate was 88% with a median follow-up of 70 months. Of 36 patients who failed, 14 had a component of local failure, and 31 had a component of distant failure. Eighteen of 31 distant failures involved metastatic spread to the abdominal cavity. Recurrence patterns by method of treatment are documented. Patients with high grade tumors do have a propensity for distant metastasis. Clinical investigation into the value of systemic therapy is necessary. PMID- 2211201 TI - Improved survival in advanced Hodgkin's disease with the use of combined modality therapy. AB - To compare the effectiveness of combined modality therapy and chemotherapy alone for the treatment of advanced Hodgkin's disease (Stages IIB-IV), records of 154 patients who achieved a complete or partial response to induction combination chemotherapy were analyzed. Sixty-seven patients received consolidation radiotherapy and 87 patients received no further treatment. Thirty of 154 patients participated in a prospective randomized trial of the Southeastern Cancer Study Group (SEG). Ten-year actuarial survival (Hodgkin's disease deaths only) was 93% for the combined modality therapy patients compared with 59% for the chemotherapy alone patients (p less than 0.0005). Combined modality therapy patients had an 87% 10-year actuarial freedom from relapse as opposed to 56% for the chemotherapy alone patients (p less than 0.0005). Relapse occurred in 33 of the chemotherapy alone patients, 28 (85%) being in sites involved at initial diagnosis. Seven combined modality therapy patients recurred with only two true in-field failures. Multi-variate analysis demonstrated treatment (combined modality) as the only variable affecting outcome. Patients prospectively treated with combined modality therapy in the Southeastern Cancer Study Group trial also showed a statistically significant improvement in both survival and freedom from relapse compared with patients receiving chemotherapy only. There was no apparent increase in toxicity from using combined modality therapy compared with chemotherapy. Three chemotherapy patients and one combined modality therapy patients developed acute leukemia. PMID- 2211202 TI - Mediastinal irradiation in combined modality therapy for Hodgkin's disease. AB - Patients with Hodgkin's disease who present with large mediastinal masses in the setting of either early or advanced stage disease are frequently treated with combined modality therapy. Policies for radiation dose to the mediastinum in these settings range from no radiation to doses in the 3600-4000 cGy range. We reviewed the charts of 50 patients treated with radiation therapy following remission induction with chemotherapy between 1979 and 1983 to determine whether the dose of radiation to the mediastinum could be correlated with mediastinal control, relapse-free, and overall survival. Patients were divided into groups with small (SM, 30 pts.) and large (LM, 20 pts.) mediastinal masses and analyzed according to whether they had received low dose (LD, less than or equal to 2500 cGy) or high dose (HD, greater than 2500 cGy) radiation to the mediastinum. The 5 year relapse-free survival (RFS) for all 50 patients was 84% (+/- 8%, 95% confidence limits). For the patients with small mediastinal masses, 5-year RFS was 81% +/- 20%, and for the patients with large mediastinal masses, 89% +/- 16%. No clear dose-response effect was observed when the outcomes of the low dose and high dose patients were compared. This was true even in the patients with large mediastinal masses although the high dose subset of this group included patients felt to be at a higher risk for relapse following chemotherapy. Nine of eleven patients with large mediastinal masses treated with chemotherapy and low dose radiation remain disease-free. There was only one isolated mediastinal relapse in the entire group of patients. Treatment was well tolerated with no acute treatment-related deaths. Two patients developed second malignancies. We conclude that combined modality therapy using low dose radiation results in excellent 5 year relapse-free survival for most small and many large mediastinal mass patients, and that it is not necessary to treat all chemotherapy patients who present with mediastinal disease with high dose radiation to achieve these relapse-free survival rates. PMID- 2211203 TI - Curative radiotherapy for laparotomy-staged IA, IIA, IIIA Hodgkin's disease: an evaluation of the gains achieved with radical radiotherapy. AB - Between 1970 and 1983, 179 patients with pathologically staged IA, IIA, and IIIA Hodgkin's disease were treated with curative radiotherapy. From 1970 to 1974, patients were treated with standard extended or total nodal field irradiation (Treatment Group 1). Since 1975, because of the high prevalence of recurrences in patients with large mediastinal mass and/or hilar disease and/or splenic involvement (LMM &/or H+ &/or S+), treatment was modified to include low-dose lung irradiation within the mantle field for those patients with LMM &/or H+ and low-dose liver irradiation within the infradiaphragmatic field for patients with S+ (radical XRT). Patients who did not have those characteristics were treated with standard radiotherapy (standard XRT). A total of 122 patients were treated from 1975 to 1983 (Treatment Group 2), of whom 61 received radical XRT and 61 received standard XRT. An analysis was done to evaluate whether the progressive improvement in outcome since 1970 at the University of Minnesota Hospital resulted from the contribution of modified treatment or from progressive improvement in treatment overall. There was a statistical improvement in recurrence-free survival (RFS) in Treatment Group 2 (Tr Gr 2) compared to Treatment Group 1 (Tr Gr 1), with 10-year RFS of 80% versus 57% (p less than 0.001 for time to event). The improvement in RFS was attributed to treatment modification consisting of radical XRT for those patients with LMM &/or S+. There was no change in RFS for those patients without LMM &/or H+ &/or S+ who were treated in Tr Gr 1 and Tr Gr 2, with 10-year RFS of 78% versus 86% (p = 0.29), respectively. However, treatment results for patients with LMM &/or H+ &/or S+ improved considerably in the radical XRT group. Comparing standard versus radical XRT, 10-year RFS was 36% versus 78% (p = 0.001), and 10-year OS was 72% versus 92% (p = 0.034). Patterns of relapse also changed for patients with LMM &/or H+ &/or S+ who were treated with radical XRT. Rather than showing a high frequency of intrathoracic recurrence as was seen in those patients with LMM &/or H+ &/or S+ after standard XRT, the relapse pattern was similar to patients without LMM &/or H+ &/or S+. Salvage treatment was well tolerated for patients who failed after radical XRT. Delayed, life-threatening effects, such as pulmonary and cardiovascular complications and SMN, were equivalent for patients in Tr Gr 1 versus 2, and for those who received standard and radical XRT.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2211204 TI - Carcinoma of the prostate stage B and C: lack of influence of duration of radiotherapy on tumor control and treatment morbidity. AB - Between 1966 and 1985, 542 of 585 patients with histologically confirmed carcinoma of the prostate, Stages B and C, were treated with definitive radiation therapy to a minimum of 6300 cGy. There were 191 Stage B patients and 351 Stage C patients. The median tumor dose for Stage B patients was 6957 cGy and for Stage C patients 7020 cGy. Daily fractions of 180 to 200 cGy were given 4 or 5 times per week with occasional rest periods of several days, usually because of side effects of radiation therapy. The minimum follow-up time was 3 years; maximum follow-up was 16.0 years, and the median was 4.8 years. In this analysis, within each stage, patients were divided into four groups based on the number of treatment days: less than or equal to 56 days (8 weeks), 57 to 63 days (9 weeks), 64 to 70 days (10 weeks), and greater than 70 days. The distribution of Stage B and Stage C patients by histologic grade and duration of therapy is fairly even within each group. The influence of duration of radiotherapy on actuarial survival, progression-free survival, pelvic control, and incidence of complications was analyzed, and no statistical difference among the four groups of patients was found. The scatterplots of pelvic failure by radiation dose and duration of radiotherapy for both Stage B and C prostate carcinoma patients did not show a correlation between failure rate and duration of radiotherapy. Tumor histologic grade did not influence the incidence of pelvic failure. In summary, within the dose range used in this analysis the overall length of radiation treatment time did not seem to affect the clinical outcome of patients with Stage B and C prostate carcinoma. PMID- 2211205 TI - Radiation therapy for AIDS-related Kaposi's Sarcoma. AB - Between March 1982 and October 1987, 375 fields in 187 patients with AIDS-related Kaposi's Sarcoma were treated in the Department of Radiation Oncology at the University of California in San Francisco (UCSF). Field sizes ranging from 2 x 2 cm to total skin received doses of 8 Gy in a single fraction to 15-40 Gy in 5-10 fractions. Seventy-four percent of the patients have died. Response to treatment was achieved in over 90% of treated fields, with a median time to progression of 21 months and an actuarial freedom from relapse at 6 months of 69% (97 patients alive). There was no difference in outcome regardless of the fractionation regimen used. Severe reactions were noted in 17% of treated fields, but this incidence was significantly lower when a single fraction of 8 Gy was used (p less than 0.001). Radiation therapy plays an important palliative role in this devastating disease. This review supports the use of a single 8 Gy fraction for all Kaposi's Sarcoma lesions of the skin. Further data regarding single fraction therapy for lesions of other sites are needed. PMID- 2211206 TI - Postoperative irradiation for the prevention of heterotopic bone: analysis of different dose schedules and shielding considerations. AB - Ninety-seven high risk hips were irradiated postoperatively for prevention of heterotopic bone (HTB) in the UCLA Department of Radiation Oncology from 1980 to 1988. Ninety-two hips in 82 patients were eligible for analysis with a minimum follow-up of 2 months and a median follow-up of 10 months. Forty-nine of the hips had porous coated ingrowth prostheses. From 1980 to 1986, 2 Gy fractions were used to deliver 20 Gy (8 hips), 12 Gy (1 hip), and 10 Gy (27 hips). Since December of 1986, 38 hips received 8 Gy in two increments and 18 hips received a single 7 Gy fraction. All porous ingrowth components were shielded with custom blocks. Six out of 92 hips developed clinically significant (Brooker grade 3 or 4 heterotopic bone). There was one clinically significant failure in 78 hips (1.3%) when irradiation was initiated before post-operative day (POD) #6 and shielding was properly placed. One clinical failure occurred in 38 hips which received 8 Gy in two increments. One clinical failure occurred out of the 18 hips treated with 7 Gy in one fraction. This failure could be related to block malposition. There were four clinical failures in the 36 hips treated with 2 Gy fractions to total doses of 10 Gy, 12 Gy, or 20 Gy. Three of these failures were associated with initiation of treatment after POD #5, and the fourth was related to block malposition. Unshielded trochanteric osteotomies resulted in five migrations and seven fibrous unions for a total non-osseous union rate of 12/36 (33%). Shielding of the remaining 28 trochanteric osteotomies resulted in a non-osseous union rate of 7% (0 migrations and 2 fibrous unions). There were no failures of union of components, and the only side effects noted in the series were the five trochanteric migrations. In conclusion, the use of 8 Gy in two increments or 7 Gy in one fraction was found to be as efficacious as conventional 2 Gy fractionation schemes with no increase in side effects. For optimal results, treatment should be implemented prior to POD #5 with shielding of the trochanteric osteotomy. Postoperative irradiation to prevent HTB can be used in hips with porous components using properly placed blocks to shield the porous region. PMID- 2211207 TI - The essential role of radiation therapy in securing locoregional control of Merkel cell carcinoma. AB - Between 1966 and 1987, 54 patients with non-disseminated Merkel cell carcinoma (MCC) were treated with curative intent at the University of Texas M. D. Anderson Cancer Center. The primary tumor site was in the head and neck in 38 patients. The majority of the patients (57%) were referred with locoregionally recurrent disease. For the whole group, survival was 30% after 5 years. Patients who presented with nodal involvement had a median survival of 13 months compared with 40 months for node-negative patients (p less than .04). Only 4/37 patients treated initially by surgery alone were locoregionally controlled, with a median time to recurrence of 4.9 months. Salvage with radiation therapy was attempted in 18 patients (after additional surgery in 14), but was successful in only four. The predominant failure pattern in this subgroup was distant metastases, occurring as a component of initial recurrence in 12/18 patients. Prior to 1982, the philosophy of initial therapy was to give postoperative irradiation only to patients with large primaries or nodal involvement. Subsequently, postoperative radiotherapy has been recommended routinely, and all five patients treated with this approach remain disease-free. In total, 31 patients (including 10 patients with gross disease) were irradiated at M. D. Anderson; only one developed an in field locoregional recurrence as an initial site of failure. However, three marginal recurrences occurred. The median dose to the primary tumor, first echelon nodes, and supraclavicular nodes was 60, 51, and 50 Gy, respectively. Our current recommendation for initial treatment is excision of the primary tumor followed by irradiation with generous fields to include the primary tumor site and draining regional lymphatics to doses of 46-50 Gy in 2 Gy fractions. For gross unresected disease, 56-60 Gy is recommended. The role of adjuvant systemic therapy remains to be defined. PMID- 2211208 TI - Adenocarcinoma of the esophagus and esophago-gastric junction: the effects of single and combined modalities on the survival and patterns of failure following treatment. AB - One hundred sixty-five patients with localized adenocarcinomas of the esophagus or esophago-gastric (EG) junction were treated with surgery alone, radiation therapy alone, chemotherapy alone, surgery followed by post-operative radiation therapy, chemotherapy, or chemosensitized radiation therapy, and chemosensitized radiation therapy alone. Patients were retrospectively evaluated for survival, control of tumor within the mediastinum, post-operative swallowing function, patterns of failure, and treatment-related morbidity. Follow-up of survivors ranges from 9-88 months (median 23 months). Chemotherapy and radiation therapy as single modalities were associated with a recurrence rate of 100%. Combined modality therapy significantly reduced the risk of local recurrence in all patient groups. Chemosensitized radiation therapy alone reduced the local recurrence rate to 48%, and surgery followed by radiation therapy reduced the local failure rate to 24%. When chemotherapy or chemosensitization was added to surgery plus radiation, the risk was further reduced to 15%. The use of combined modality therapy was also found to extend the survival of patients without excessive toxicity. Median survival was shortest among the group treated with radiation alone (5 months) and intermediate among patients following chemosensitized radiation alone (10 months) or complete surgical resection alone (15 months). Patients treated with all three modalities had the longest median survival (21 months). Based on this experience, the optimum treatment of these patients appears to include aggressive attempts at surgical resection with chemosensitized radiation therapy. Excellent palliation can also be achieved in unresectable patients with chemosensitized radiation therapy with a smaller chance for long term survival. PMID- 2211209 TI - High dose, external beam and intraoperative radiotherapy in the treatment of resectable and unresectable pancreatic cancer. AB - Ninety patients with pancreatic cancer were treated by external beam radiotherapy (EBRT) and/or intraoperative radiotherapy (IORT) with or without surgical resection of the tumor, and the results were compared with those of a historical control comprising 112 patients treated by surgery alone. At an early stage of this study, postoperative EBRT (50-60 Gy) or IORT (25-33 Gy) was given alone, but recently the two modalities have been combined. The combination of high doses of EBRT and IORT was well tolerated provided that the gastrointestinal tract was not irradiated during IORT. Although EBRT plus IORT appeared to yield better results than either EBRT or IORT alone, the difference was not significant on multivariate analysis, and patients receiving EBRT, IORT, or EBRT + IORT were grouped together. Patients receiving radiotherapy in addition to macroscopically curative surgery had a slightly longer median survival time (14 months) than those receiving curative surgery alone (10 months), but the 3-year survival rate was similar (21% vs. 19%). In patients who underwent noncurative resection, the median survival time was significantly longer for the irradiated group (12 months) than for the control group (6.5 months). Also, in patients with unresectable lesions but no distant metastases, irradiation prolonged the median survival time significantly (8 vs. 3.5 months). In this group, there was one 5 year survivor, who received EBRT of 55 Gy plus IORT of 30 Gy to his unresectable pancreatic body lesion. Patients with metastases were also treated for palliation of symptoms, but it was found that irradiation prolonged the median survival time even in such cases (4.5 vs. 2.5 months). Based on these results, we plan to use EBRT plus IORT in all pancreatic cancer patients with no metastases. PMID- 2211210 TI - 90Y.B72.3 against pancreatic cancer: dosimetric and biological analysis. AB - Nude mice xenografted with a human pancreatic carcinoma cell line were injected with yttrium-90 (90Y) conjugated to diethylene triaminepenta acetic acid (DTPA) alone, and DTPA covalently linked to a monoclonal antibody, B72.3. The animals were sacrificed in temporal sequence to evaluate isotope distribution. Dosimetry was carried out using the principles outlined in MIRD and ICRU Report 32. Results are expressed as percent uptake per unit mass in organs and tumor and as relative absorbed dose normalized to 90Y uptake in liver at 7 hr. When conjugated to B72.3, an 8-fold increase in isotope localization in the tumor was noted by 24 hr. When the relative absorbed dose is calculated for 90Y and 90Y.B72.3, a 26 fold increase in tumor dose is noted for the 90Y conjugate. Normal tissues show no to modest (less than 5x) enhanced dose with 90Y.B72.3. B72.3, therefore, deserves further investigation as a potential monoclonal antibody for targeting therapeutic radioisotopes and possibly diagnostic radioisotopes to pancreatic cancer. Radiobiological aspects of the low dose rates from radioimmunotherapy are discussed. PMID- 2211211 TI - Drug resistance following irradiation of RIF-1 tumors: influence of the interval between irradiation and drug treatment. AB - RIF-1 tumors contain a small number of cells (1 to 100 per 10(6) cells) that are resistant to 5-fluorouracil, methotrexate, or adriamycin. The frequency of drug resistant cells among individual untreated tumors is highly variable. Radiation, delivered in vivo at doses of 3 to 12 Gy, increases the frequency of methotrexate and 5-fluorouracil-resistant cells, but not the frequency of adriamycin resistant cells. The magnitude of induction of 5-fluorouracil and methotrexate resistance shows a complex dependence on the radiation dose and on the interval between irradiation and assessment of drug resistance. For a dose of 3 Gy, induced 5-fluorouracil and methotrexate resistance is seen only after an interval of 5 to 7 days, whereas for a dose of 12 Gy, high levels of induced resistance are observed 1 to 3 days after irradiation. The maximum absolute risk for induction of resistance is 4 per 10(4) cells per Gy for methotrexate, and 3 per 10(6) cells per Gy for 5-fluorouracil. These results indicate that tumor hypoxia may play a role in the increased levels of drug resistance seen after irradiation, and that both genetic and environmental factors may influence radiation-induction of drug resistance. These studies provide essential data for models of the development of tumor drug resistance, and imply that some of the drug resistance seen when chemotherapy follows radiotherapy may be caused by radiation-induced drug resistance. PMID- 2211212 TI - Radiation fractionation sensitivity of epiphyseal cartilage in a weanling rat model. AB - Tibial growth at 100 days of age was measured in Sprague-Dawley rats treated at 21 days to the proximal tibia with various courses of fractionated radiation. In split-dose and multiple-fraction experiments, a minimum interval of 5-6 hr was required to achieve maximal sparing of growth arrest. Total doses required to reduce growth to 80% of untreated controls were computed from dose-response curves for fractionated radiation (dose/fraction 1.0-10 Gy). When fitted to a linear-quadratic model of radiation response the data described an estimated alpha/beta of 4.47 (95% C.I. (3.71, 5.23) Gy). This value suggests that the fractionation sensitivity of the epiphyseal plate is substantially greater than that of most neoplasms, predicting a favorable therapeutic gain with the use of hyperfractionated radiation therapy. PMID- 2211213 TI - Effect of Fluosol-DA 20% and oxygen on response of C57BL/6 mice to whole-body irradiation. AB - Normal tissue effects in mice due to combinations of a perfluorochemical emulsion, Fluosol-DA 20%, 100% oxygen, and whole-body irradiation were investigated. Eight-to-10-week-old C57BL/6 male mice were injected via the tail vein with 10 ml/kg of Fluosol-DA with and without subsequent exposure to oxygen for 60 minutes. Animals then received graded doses of whole-body radiation (4 MV photons) at a dose rate of 2.85 +/- .015 Gy/minute. Using linear regression analysis, the lethal doses of radiation to 50% and 10% of the animals within 30 days in the absence of Fluosol-DA and oxygen were 8.35 Gy (95% c.l.:7.77-8.93 Gy) and 6.73 Gy (95% cl.:6.21-7.25 Gy), respectively, and were unaffected by Fluosol DA and/or oxygen pre-treatment. However, Fluosol-DA given alone or in combination with oxygen produced increased balding and decreased graying incidence in mice within 60 days, and resulted in depressed weight gain 15 to 60 days post treatment. Normal tissue effects due to administration of Fluosol-DA and oxygen in combination with whole-body irradiation have been demonstrated but appear minimal compared to other anti-tumor modalities currently under investigation. PMID- 2211214 TI - Simultaneous localized 915 MHz external and interstitial microwave hyperthermia to heat tumors greater than 3 cm in depth. AB - A technique for heating superficial lesions extending to a depth greater than 3 cm using 915 MHz electromagnetic energy is described. It is well established that with external microwave applicators operating at 915 MHz, it is only possible to heat adequately up to a maximum depth of 3 cm. However, it is demonstrated that by implanting additional layers of interstitial microwave antennas (1.5 cm spacing) at required depths greater than 3 cm, and by simultaneously exciting these applicators as well as an external applicator, it is possible to extend the depth of heating at this frequency. A large neck node was successfully heated when this combined technique was used. The details of the method and the equipment used are described. Specific Absorption Rate (SAR) values and temperature distributions obtained during the four treatments delivered to the patient are also presented. This technique can be used in situations where it is not possible to perform extensive interstitial implantation, and in institutions where hyperthermia equipment for heating deeper lesions is not available. PMID- 2211215 TI - The modification of specific absorption rates in interstitial microwave hyperthermia via tissue-equivalent material bolus. AB - Patterns of specific absorption rates generated by interstitial, microwave antenna arrays must be experimentally ascertained and quantified to facilitate their clinical incorporation. Phantom studies involved the use of four single gap, coaxial antennas oriented in a 2 cm square array. These dipoles were driven in phase by a microwave generator at a frequency of 915 MHz. The inherent limitations in modifying the specific absorption rate patterns were addressed with the addition of bolus to the phantom. These additions of Guy's muscle tissue equivalent material were made either proximal or distal to the phantom proper. Experiments conducted in the presence and absence of tissue-equivalent material bolus showed the ability to achieve broader bands of 50% power deposition in certain bolus conditions. These heating patterns were sufficiently reproducible and predictable to warrant clinical application of the bolus addition. A through and-through method of catheter implantation allowed for bolus addition when deemed necessary. Treatments with veterinary and human patients using the bolus method to modify heating patterns yielded augmented patterns of power deposition. The effective length of the antennas that would radiate efficiently was essentially broadened via introduction of a microwave-interacting medium. As a result of the tissue equivalent material's ability to absorb microwave power, it was necessary to interpose minimally-interactive styrofoam spacers to limit heat transfer effects at the tissue-bolus interfaces. PMID- 2211216 TI - Radiotherapy with and without cisplatin in bladder cancer. AB - From October 1985 to December 1988, 67 patients with invasive bladder carcinoma T1-4 N0-2 M0 were treated with irradiation (50.4 Gy in 28 fractions in 6 weeks) and simultaneous cisplatin (25 mg/m2 per day on 5 consecutive days in the first and fifth irradiation week). After transurethral resection and irradiation plus cisplatin, complete remissions were achieved in 8/11 T1-, 14/16 T2-, 27/36 T3- and 1/4 T4-tumors. The complete remission rate 6 weeks after treatment according to the extent of preceeding transurethral surgery (TUR) was: R0: 67% (8/12); R1: 83% (20/24); R2: 70% (21/30); Rx: 1/1. In patients with incomplete TUR (R1-2), the complete remission rate was 76% (41/54). This was superior to the results of a historical control (76% vs. 45%, p less than 0.01). The estimated 3-year survival according to T-stage was: T1: 73%, T2-3: 68%, T4: 25%. The overall 3 year survival was unchanged as compared to our historical control (66% each). Severe complications have not been observed. We conclude that cisplatin will likely increase the local control rate after incomplete transurethral surgery. An improvement of survival seems unlikely. PMID- 2211217 TI - Combined 5-fluorouracil and irradiation for transitional cell carcinoma of the urinary bladder. AB - Thirty-four patients have completed treatment on a bladder-preservation protocol using primary irradiation combined with infusion 5-fluorouracil (5-FU). 4,000 cGy pelvic irradiation was delivered in 5 weeks, with 1,000 mg/m2/day of 5-FU administered as a 96 hr infusion on days 1-4 of week 1 and 4. After a 3-week rest period, patients eligible for cystectomy underwent cystoscopy and biopsy. Those with residual tumor underwent cystectomy, and those without tumor received an additional cycle of chemotherapy and irradiation. Patients ineligible for cystectomy for reasons medical, surgical, or refusal received a third cycle without the 4-week delay or re-evaluation. With a median follow-up of 18 months (range 2-45 months), and with 25/34 patients having T3 (16) or T4 (9) tumors, 17 patients are NED, 4 have died of intercurrent deaths, 7 have died with bladder cancer, and 6 are alive with tumor (2 confined to the bladder). The actuarial cancer-specific survival for the entire group of patients is 64% (+/- 12%) at 45 months, with a freedom from relapse of invasive cancer of 54% (+/- 10%). Twenty four of the 34 patients retained intact bladders, with 20/24 reporting entirely normal voiding. Of 18 potential surgical candidates, 13/16 (81%) who underwent pathologic re-staging after 2 cycles of chemoradiotherapy had no histologic evidence of residual cancer. Of these 13 patients, 8 remain NED and 2/13 have locally recurrent non-invasive tumors only. Treatment was well-tolerated, with 28/34 patients having received 100% of the planned 5-FU and 34/34 having received greater than 80%. This regimen appears more successful than radiotherapy alone in achieving complete tumor responses, and is an attractive alternative for patients who are unable to receive more aggressive chemotherapy/radiation combinations. PMID- 2211218 TI - Invasive carcinoma of the uterine cervix in women age 25 or less. AB - The incidence of cervix cancer in young women appears to be increasing. However, the influence of young age on prognosis remains unknown. There is almost no information on the prognosis of very young women, age 25 years or less, with invasive cervical carcinoma. From April 1969 to June 1987, 40/2195 (1.8%) patients, age 25 years or less, with invasive carcinoma of the uterine cervix were diagnosed, staged, and treated at our institution. Median age was 24.7 years (range 20.7 to 25.9 years). Distribution by FIGO stage was: Stage IA 7 (18%), Stage IB 23 (58%), Stage II 4 (10%), Stage III 4 (10%), and Stage IVA 2 (4%). Thirty-four (85%) patients had squamous cell carcinoma and six (15%) had adenocarcinoma. Treatment consisted of radical hysterectomy for all Stage IA patients, radical hysterectomy with or without bilateral pelvic node dissection for the 12 early Stage IB patients, and radiation with or without surgery for the remaining 11 Stage IB patients and all Stage II-IVA patients. Median follow-up was 122 months (range 13.2-190.6 months). Five-year disease-free survival rates were: Stage IA 100%; Stage IB 54.8%; and Stage II-IVA 13.7%. Five-year disease free survival for the Stage IB patients with squamous cell carcinoma age 25 years or less was 64.7%, compared with 83% for women of all ages with Stage IB squamous histology treated at our institution. Seven of 23 Stage IB patients suffered regional recurrence only, one a local recurrence only, one a distant recurrence only, and one a combined recurrence. Seventy-five percent of these patients presented with Stage I disease; however, one-third died from their disease. The major site of failure was in the pelvis only. This, coupled with the low risk of long-term serious complications, suggests that more aggressive pelvic therapy may result in improved disease-free survival. PMID- 2211219 TI - Prospective study of long-term pulmonary manifestations of mantle irradiation. AB - Given the high cure rate of patients with Hodgkin's disease, the complications related to therapy take on great significance. Mantle irradiation to the thorax is used in virtually all patients with early stage Hodgkin's disease. Prior studies of patients receiving mantle irradiation demonstrated short-term (up to 24 months) abnormalities of pulmonary function. In the present study, we prospectively studied 13 patients for up to 60 months after irradiation only with serial pulmonary function tests, arterial blood gas tests, diffusing capacity of carbon monoxide, chest radiographs, and ventilation-perfusion scans. No respiratory symptoms attributable to therapy were noted. Frequent radiographic changes (62%) were found consisting of apical fibrosis, paramediastinal fibrosis, or pleural thickening. Two patients developed an asymptomatic spontaneous pneumothorax that resolved with conservative management. Ventilation-perfusion scans often (73%) revealed decreased perfusion to the lung apices with associated ventilatory deficits in one-half of these patients. Patients with intrathoracic disease had decreased lung volumes prior to therapy, and lung volumes did not change following irradiation. Lung mechanics were normal throughout the study. Gas exchange at rest was normal in patients with extrathoracic disease. Patients with intrathoracic disease often presented with an abnormal arterial PO2 and widened alveolar-arterial partial pressure gradient for oxygen. However, these parameters normalized by 9 months after therapy. Despite the frequent development of radiographic and V/Q scan abnormalities in the lung apices, patients tolerated mantle radiotherapy remarkably well. In fact, patients with intrathoracic disease demonstrated improved gas exchange at rest following therapy. PMID- 2211221 TI - Radiation effects on left ventricular function and myocardial perfusion in long term survivors of Hodgkin's disease. AB - We evaluated systolic and diastolic indices of left ventricular performance by radionuclide angiocardiography and myocardial perfusion with exercise/rest thallium scintigraphy in 16 patients previously irradiated for Hodgkin's disease. These commonly used indices of left ventricular (LV) performance included LV ejection fraction (LVEF) as a measure of systolic function, and LV peak filling rate (PFR) as a measure of diastolic function. The presence of coronary artery disease (CAD) was evaluated by ECG treadmill testing (13 patients) and by quantitative planar thallium scintigraphy (12 patients). Patients were 16-38 years old (mean 24.9 +/- SD 6.2) at the tim eof irradiation, and were evaluated 2.5-21.5 years (mean 9.3 +/- 6.3) after radiation therapy (RT). RT was delivered with beam energies of 2-18 MV, equally weighted AP-PA mantle fields with both fields treated daily for most patients (13 patients), and fraction sizes of 1.5 2.0 Gy. Six patients received radiation to th entire cardiac volume, most commonly via left-sided partial transmission lung blocks (PTLB). Patient data were analyzed according to the volume of heart treated. Individuals who had the entire cardiac volume irradiated were assigned to group I (N = 6), and those patients who had some portion of the heart shielded throughout treatment comprised group II (N = 10). In this series, no perfusion defects were evident in either group by quantitative planar thallium scintigraphy. Mean LVEF for all patients studied was 60% (normal LVEF greater than or equal to 50%). Patients in group I had a lower mean LVEF than those in group II, 55 +/- 4% versus 63 +/- 6% (p = 0.01). Mean PFR for all patients studied was normal at 3.5 EDV/sec (normal PFR greater than or equal to 2.54 EDV/sec). Patients in group I had a lower mean PFR than those in group II, 3.0 +/- 0.6 vs 3.8 +/- 0.7 EDV/sec (p = 0.04). Thus, patients irradiated to large cardiac and pulmonary volumes had lower LVEF and PFR within the normal range compared to patients who had some portion of the cardiac volume shielded. These differences are statistically significant in the relatively small groups studied but do not appear to be associated at the present time with clinically significant effects. PMID- 2211220 TI - Is pelvic irradiation necessary in stage III1A Hodgkin's disease? AB - Eighteen patients with pathologic Stage (PS) III1A Hodgkin's disease were treated with mantle and para-aortic field radiation therapy alone between 1973 and 1988. The median follow-up time is 84 months (range 20-174 months). The 5-year survival and relapse-free survival rates are 76 and 82%. Six patients had extensive splenic involvement or bulky mediastinal adenopathy, and three have relapsed and are dead of disease. Of the other 12 patients, only one has had recurrence of disease and died. Patients with PS III1A Hodgkin's disease are good candidates for mantle and para-aortic radiation therapy only, provided that they do not have extensive splenic involvement or large mediastinal adenopathy. PMID- 2211222 TI - Pre and posttreatment evaluation of sexual function in patients with adenocarcinoma of the prostate. AB - Twenty-seven patients with adenocarcinoma of the prostate, and available partners, were interviewed to qualitatively and quantitatively assess their level of sexual function prior to and 12 months after radiotherapy. Assessments were made using the Derogatis Interview for Sexual Functioning (DISF). Five domains of sexual functioning are measured: sexual fantasy, arousal, experience, orgasm, and drive. Prior to therapy 17 of 27 patients (62.9%) were considered impotent. There were eight patients with a DISF score of less than 20 who were impotent. Six patients had a DISF score of greater than 47 and were considered potent. Of the patients with DISF scores between 20-47 four were potent, and nine were impotent. Post radiation therapy three of the patients considered potent (with a score greater than 47) maintained their potent status. Four patients considered impotent prior to therapy became potent after therapy. All patients with a score less than 20 prior to radiation therapy remained impotent after therapy. Results indicate that an objective evaluation of sexual function pre treatment is necessary to determine the effect of radiotherapy. Our method of qualitative assessment of sexual function was easy to implement, was reproducible and could be used to evaluate long-term effects of radiotherapy on sexual function. Of the patients presenting for radiotherapy, 62.9% were impotent. Twelve months after radiation therapy 19 of 27 (70.3%) were impotent. PMID- 2211223 TI - Transperineal templates for brachytherapy treatment of pelvic malignancies--a comparison of standard and customized templates. AB - A technique is described for the design and construction of customized templates for transperineal implants and interstitial hyperthermia of pelvic malignancies. The design of the template and the distribution of the transperineal Iridium-192 seed ribbons are based on prior optimization of the dose distribution. The target volume is defined by means of pelvic examination and pertinent radiographic studies including a CT. The pelvic CT study is obtained with a plastic obturator in the rectum or the vagina. The obturator is used as a reference structure for aligning the target contour from each image plane to form a composite 2 dimensional contour of maximum tumor extent in a plane perpendicular to the obturator. Dose distributions are calculated to determine the placement of the Iridium-192 seed ribbons in the template. Laparoscopic guidance is used for actual placement of brachytherapy source needles together with a rectal or vaginal obturator to stabilize the template and to assure that the needle placement conforms with the planned geometry. Dose distributions for 10 consecutive patients calculated for customized templates as well as for five commercially available standard templates show that the customized templates are superior to standard templates in that the planned dose distribution matches the configuration of the target volume and is more uniform than with standard templates. PMID- 2211224 TI - Beam's eye view based prostate treatment planning: is it useful? AB - Prostate cancer is a common malignancy often treated with radiation therapy. Treatment optimization may improve local control while reducing acute and long term complications. We routinely obtained CT scans on prostate cancer patients in treatment position after simulation. We analyzed the impact and implications of using our 3-D Beam's Eye View (BEV) capability on field definition and blocking for 12 consecutive patients. Conclusions include: (a) it is necessary to use multiple bony landmarks to align BEV images with simulator films; (b) it is difficult to enter volumes precisely, that is, the exact inferior extent of prostate; (c) Beam's Eye View-based plans show more individual variability in field size and position than are allowed for by recommendations in the literature; and (d) in this small series we found no significant correlation between prostate volume and clinical staging. In addition, computerized Beam's Eye View capability enables us to do normal tissue dosimetry. We have used Dose Volume Histograms (DVH) to study the impact of Beam's Eye View on optimization of dose to the bladder and rectum while adequately treating the prostate, with or without the seminal vesicles. Dose Volume Histograms using Beam's Eye View are compared with Dose Volume Histograms using target volumes from the literature. The results will be discussed, as well as the relative advantages of using Beam's Eye View for prostate cancer on a routine basis. PMID- 2211225 TI - Perineal template techniques for interstitial implantation of gynecological cancers using the Paris system of dosimetry. AB - Since 1984, perineal template/needle techniques for interstitial implantation of gynecologic cancer-cervix, vagina, vulva-have been developed at the Peter MacCallum Cancer Institute. The Paris System of dosimetry has been used resulting in greater dose homogeneity, fewer needles and radioactive sources and considerable simplification and ease of implantation compared with comparable techniques developed in the United States. Principles and techniques of implantation are described in detail. PMID- 2211226 TI - 3-D beams need 3-D names. PMID- 2211227 TI - Elective irradiation of the para-aortic nodes in squamous cell carcinoma of the uterine cervix. PMID- 2211228 TI - Brachytherapy: a clinical dilemma. PMID- 2211229 TI - Hodgkin's disease: the right dose. PMID- 2211231 TI - Optimal treatment of epidemic Kaposi's sarcoma. PMID- 2211230 TI - The caucus race: regionalism in the treatment of Hodgkin's disease. PMID- 2211232 TI - Postoperative irradiation for prevention of heterotopic bone after total hip arthroplasty. PMID- 2211233 TI - The current status of combined modality treatment containing chemotherapy in patients with esophageal cancer. PMID- 2211235 TI - Oblique sections need 3-D names also. PMID- 2211234 TI - Chemo-radiation therapy of bladder cancer. PMID- 2211236 TI - Do superior sulcus tumors have a better prognosis than other lung cancer sites? PMID- 2211237 TI - A new staging system for endometrial carcinoma. PMID- 2211238 TI - Pretreatment evaluation of sexual function in patients with adenocarcinoma of the prostate. AB - Forty-three patients with adenocarcinoma of the prostate and available partners were interviewed to assess qualitatively and quantitatively their levels of sexual functioning prior to radiotherapy. The mean age was 67.7 years (58-80 years). The Derogatis Interview for Sexual Functioning (DISF) was the evaluation used. The Derogatis Interview for Sexual Functioning measures five domains of sexual functioning: sexual fantasy, arousal, experience, orgasm, and drive. Twenty-seven of the 43 (62.7%) patients evaluated were considered impotent. Fifteen of the 27 patients scored low in all five domains of sexual functioning even though they could achieve erection but they were unable to maintain erection throughout the phases of the sexual response cycle. Twelve of the 27 patients had scored 0 on sexual arousal and orgasm, thus had no ability for erection. Sixteen of the 43 (37.2%) patients were considered potent. This group of patients had achieved erection throughout the phases of sexual cycle and scored adequately in all five domains of sexual functioning. Patients with DISF score less than 20 were impotent. Those with a Derogatis Interview for Sexual Functioning score of greater than 45 were potent. Only 6 of 19 patients with scores between 20 and 45 were potent. The Derogatis Interview for Sexual Functioning score was highly prognostic for impotence, (p = .002) was easy to use and could be used for follow up of the effect of therapy on sexual function in patients with adenocarcinoma of the prostate. Patients who present for radiation therapy are older, 50% are on cardiac or antihypertensive medication, and the majority (62.7%) are already impotent prior to therapy. PMID- 2211239 TI - Histological and immunohistochemical prediction for local control of cervical squamous cell carcinoma treated with radiotherapy alone. AB - Predictability of local control following radiotherapy was evaluated with morphological methods such as histology and immunohistochemistry for 36 cervical squamous cell carcinomas. All these patients showed viable cancer cell predominance on the specimens excised with drill biopsy after radiation therapy. These specimens were stained with routine haematoxylin and eosin staining as well as with antibodies against epithelial membrane antigen (EMA), carcinoembryonic antigen, and S-100 protein. Five histological features, the number of the cancer nests per 22.5mm2 section, stromal reaction, space formation in the cancer nests, foamy cell or foreign body giant cell (FBG) clusters, and epithelial membrane antigen reactivity on the specimens excised after radiation therapy, were significantly related to the local control probability. Namel, less than 20 cancer nests, granulomatous stroma, presence of the space formation, absence of the foamy cell or foreign body giant cell clusters, and epithelial membrane antigen negativity were favorable for local control of the cervical cancer with radiation therapy. These data suggested that radiation sensitivity of cancer and stromal reaction for drainage of the degenerated cancer debris were important for local control of the tumors. PMID- 2211241 TI - An application of dose volume histograms to the treatment of intrahepatic malignancies with radiation therapy. AB - A clinical protocol was designed that used the dose volume histogram (DVH) of the normal liver to determine the dose of radiation to be delivered to patients with intrahepatic malignancies. The dose given to the tumor depended on the volume of normal liver that could be excluded from the boost field: 45 Gy if more than 50% of the normal liver could be excluded and 60 Gy if more than 75% of the normal liver could be excluded. Thus, dose prescription depended on the ability to perform, on a routine basis, three-dimensional (3-D) treatment planning with dose volume histogram generation. A total of 36 patients have been entered onto this study. Twenty-one of 25 patients (84%) with disease that could be delineated on CT scan were eligible for boost treatment. Successive planning attempts often produced plans which qualified for boost therapy when the initial estimate had been that boost treatment would not be possible. Patients with large tumors were sometimes able to receive boost treatment, demonstrating that individualized planning was required. These results show that intrahepatic tumors can be safely treated with high doses of radiation when dose prescription is guided by the dose volume histogram of the normal liver. Furthermore, this approach strongly promotes an active role in treatment planning, since creative planning often permitted the delivery of higher doses to the tumor. PMID- 2211240 TI - A nondivergent three field matching technique for breast irradiation. AB - Effective radiation therapy to intact breasts requires the delivery of adequate dose to a large target volume using complex beam arrangements. A semi-empirical method is described to determine the correct gantry, collimator, and couch positions for a geometrically accurate field match among adjoining radiation beams. The technique uses a metal rod and chain combination to aid determination of the proper couch setting under remote fluoroscopy control. A couch position error of more than half a degree is easily detectable by this technique. PMID- 2211242 TI - Evaluation of a commercial diode monitor for mailed quality control of therapy units. AB - A commercial diode dosimeter was evaluated for use in a mailed radiotherapy quality control package. The quality control package contained the commercial diode dosimeter and four thermoluminescent dosimeters to measure the given dose, and it also contained a photographic film to measure the light/radiation field coincidence. The film also served as a backup dosimeter. Twenty small Midwestern hospitals participated in field measurements; approximately half of the hospitals had a consulting physicist and the others had one full-time physicist. Each hospital was asked to deliver 1.5 Gy (150 rads) to the device, which was returned to our laboratory for evaluation. Reliable results were obtained from three measurements at each hospital at about 3-month intervals. The diode dosimeter was more precise than thermoluminescent dosimeters or film. PMID- 2211243 TI - Virtual simulation in the clinical setting: some practical considerations. AB - Virtual simulation departs from normal practice by replacing conventional treatment simulation with 3-dimensional image data and computer software. Implementation of virtual simulation requires the ability to transfer the planned treatment geometry from the computer to the treatment room in a way which is accurate, reproducible, and efficient enough for routine use. We have separated this process into: (a) immobilization of the patient; (b) establishment and alignment of a practical coordinate system for the patient/couch system; and (c) setup of the patient/couch been addressed by the use of hemi- or full-body foam casts, the second by use of an alignment jig on the treatment couch, and the third with the aid of a patient coordinate system referenced to easily located landmarks. Phantom studies and clinical practice have shown these techniques to be practical and effective within reasonable clinical bounds. PMID- 2211244 TI - Effects of fat thickness on heating patterns of the microwave applicator MA-151 at 631 and 915 MHz. AB - Previous studies showed that the surface heating patterns of the MA-151 applicator on a 2 cm fat and 10 cm thick muscle phantom had center heating at 581 and 930 MHz and two hot spots near the edges of the applicator at 657 and 779 MHz. The hot spots at 657 MHz were consistent with two blisters on a patient's thigh. Since the heating patterns on muscle only showed good center elliptical heating at all frequencies, in this study we have investigated the effects of fat thickness on the heating patterns. Thermograms of fat and muscle surfaces were taken on phantoms with 0, 0.25, 0.5, 1, and 2 cm thick fat exposed to 631 or 915 MHz energy. The 631 MHz was selected to provide reasonable energy coupling for all phantoms. At 631 MHz, two hot spots were evident on all fat surfaces. The pattern on the muscle surface under the 0.25 cm fat did not show two hot spots, but the heating was elongated in the E-field direction. At 915 MHz, the heating was elongated on the surface of the 0.25 and 2 cm fat, and two hot spots were observed on the 0.5 and 1 cm fat surfaces. However, the muscle heating was elliptical in all cases. The ratio of muscle to fat heating decreased as the fat thickness increased. At 0.5 cm fat the ratio was about 1. These results indicate that fat thickness influences heating in muscle. During treatment with this applicator, surface temperature probes should be placed over potential hot spots. Surface cooling is desirable for heating tumors beneath the fat. PMID- 2211245 TI - Cell repopulation and overall treatment time. AB - Prolongation of the overall treatment time in radiotherapy, especially of squamous cell carcinomas of the head and neck, decreases the chances of cure. This is most likely because of the proliferation of surviving clonogenic tumor cells between dose fractions. Between the 3rd and 7th week of conventional radiotherapy of head and neck cancers, on average 0.5 to 0.7 Gy are lost per day by repopulation. As this represents an average value, repopulation may be even more efficient in subgroups of faster tumors. There is little information on repopulation rates during the first 2 weeks of radiotherapy. Prolongation of the overall treatment time in radiotherapy helps to avoid severe side effects from acutely responding tissues, especially oral mucosa. This sparing effect of increasing overall treatment time is mainly caused by the regeneration of mucosal stem cells and transit cells. This repopulation is slow in the first 2 weeks and accelerates dramatically thereafter. The nature of the trigger for acceleration is not known but seems to be related to a critical threshold of acute tissue hypoplasia and the development of the inflammatory reaction of the connective tissue. It is not known whether accelerated tumor repopulation is stimulated by the same or a similar mechanism as the normal epithelium. During accelerated repopulation the oral mucosa is able to compensate a considerably higher proportion of the daily dose fraction than the tumor. These factors have to be taken into account when treatment strategies are designed to cope with the problem of accelerated repopulation. PMID- 2211246 TI - Optimization of uncomplicated control for head and neck tumors. AB - Almost 200 patients have been treated for head and neck tumors at two different dose levels. Based on the clinically observed probabilities for tumor control and fatal normal tissue complications at the two dose levels, the dose giving maximum uncomplicated control has retrospectively been calculated and compared with the clinical data. A Poisson statistical model for control and complications has been used including a correlation parameter, delta, to describe the fraction of patients where control and complications are statistically independent. The clinically observed probability of uncomplicated tumor control, P+, is consistent with only a small fraction of the patients treated being statistically independent (delta = 0.2 or 20%). Customarily, 100% of the patients are assumed to be statistically independent with regard to tumor control and normal tissue complications. More precisely, the clinical data are consistent, with almost 20% of the patients being significantly more sensitive to radiation since they gain local tumor control but simultaneously suffer fatal complications. An even larger fraction of the patients (almost 30%) seemed to be more resistant to radiation, showing neither serious treatment complications nor control of the local tumor growth. It is suggested that if these patient groups could be identified by a predictive assay for the radiation sensitivity of their normal tissues and preferably also for their tumors, the uncomplicated tumor control could be increased by about 20%. This figure is based on the actuarial survival of the patients and has been corrected for the inevitable uncertainty in dose delivery. It is also pointed out that about 20% of the patients can never be saved by a predictive assay because of the considerable statistical variance associated with the Poisson process and the eradication of the last clonogenic tumor cell. Finally, note that the possible existence of radiation sensitive and resistant patient groups is consistent with known genetic deficiencies such as ataxia telangiectasia for the sensitive patients and the existence of repair efficient head and neck tumors that are unusually efficient in repairing double strand breaks. If such sensitive and resistant patient groups do exist, it should be sufficient to perform a predictive assay on normal tissues alone avoiding the often impossible task of sampling the most radiation resistant tumor cell line. PMID- 2211247 TI - Local recurrence after breast-conserving surgery and radiotherapy: what have we learned? PMID- 2211248 TI - Creating life on the plateau: reproductive potential in survivors of childhood Hodgkin's disease. PMID- 2211249 TI - Controversial issues in the management of cervical metastases. PMID- 2211250 TI - Primary radiotherapy and chemotherapy for locally advanced breast cancer. PMID- 2211251 TI - Multimodality treatment for inflammatory breast cancer. PMID- 2211252 TI - Principles of oncologic intervention. PMID- 2211253 TI - Isolated local-regional recurrence of breast cancer following mastectomy: radiotherapeutic management. AB - Two hundred twenty-four patients with their first, isolated local-regional recurrence of breast cancer were irradiated with curative intent. Patients who had previous chest wall or regional lymphatic irradiation were not included in the study. With a median follow-up of 46 months (range 24 to 241 months), the 5- and 10-year survival for the entire group were 43% and 26%, respectively. Overall, 57% of the patients were projected to be loco-regionally controlled at 5 years. The 5-year local-regional tumor control was best for patients with isolated chest wall recurrences (63%), intermediate for nodal recurrences (45%), and poor for concomitant chest wall and nodal recurrences (27%). In patients with solitary chest wall recurrences, large field radiotherapy encompassing the entire chest wall resulted in a 5- and 10-year freedom from chest wall re-recurrence of 75% and 63% in contrast to 36% and 18% with small field irradiation (p = 0.0001). For the group with recurrences completely excised, tumor control was adequate at all doses ranging from 4500 to 7000 cGy. For the recurrences less than 3 cm, 100% were controlled at doses greater than or equal to 6000 cGy versus 76% at lower doses. No dose response could be demonstrated for the larger lesions. The supraclavicular failure rate was 16% without elective radiotherapy versus 6% with elective radiotherapy (p = 0.0489). Prophylactic irradiation of the uninvolved chest wall decreased the subsequent re-recurrence rate (17% versus 27%), but the difference is not statistically significant (p = .32). The incidence of chest wall re-recurrence was 12% with doses greater than or equal to 5000 cGy compared to 27% with no elective radiotherapy, but again was not statistically significant (p = .20). Axillary and internal mammary failures were infrequent, regardless of prophylactic treatment. Although the majority of patients with local and/or regional recurrence of breast cancer will eventually develop distant metastases and succumb to their disease, a significant percentage will live 5 years. Therefore, aggressive radiotherapy should be used to provide optimal local regional control.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2211254 TI - Regional nodal irradiation in the conservative treatment of breast cancer. AB - At this institution conservative treatment of breast cancer was begun in the 1960's. The following analysis represents our experience through 1984 with specific reference to the management of the regional lymph nodes. A total of 432 patients with clinical stage I and II breast cancer were treated between 1962 and 1984 with lumpectomy and radiation therapy. The breast was treated with tangential fields to a median dose of 4800 cGy and electron conedown to a total tumor bed dose of 6400 cGy. Axillary dissection was not routinely performed, particularly in the earlier years. More recently, axillary dissection has been used with increasing frequency if it was felt that the results of the dissection would influence systemic treatment. One hundred eighty-seven patients (43%) underwent axillary dissection (30% pathologically positive) and routinely received regional nodal irradiation (median dose 4600 cGy) to the internal mammary and supraclavicular lymph nodes. Two hundred forty-five patients (57%) did not undergo axillary dissection and routinely received regional nodal irradiation to the internal mammary, supraclavicular, and entire axillary regions to a total median dose of 4600 cGy. As of May 1989 with a median follow-up of 7.5 years, there have been a total of 12 nodal failures for an actuarial nodal control rate of 97% at 5 years and 96% at 10 years. The actuarial 5-year regional nodal control rate was the same for both the group of patients receiving regional RT alone without axillary dissection and the group of patients receiving axillary dissection and supraclavicular/internal mammary radiation. There has been minimal morbidity associated with this treatment policy. We conclude that regional nodal irradiation as described above, with or without axillary dissection, results in a high rate of regional nodal control and minimal treatment morbidity in patients undergoing conservative treatment of early stage breast cancer. PMID- 2211255 TI - Gonadal status and reproductive function following treatment for Hodgkin's disease in childhood: the Stanford experience. AB - To ascertain the impact of therapy on gonadal function and reproductive outcome among children treated for Hodgkin's disease, we reviewed the experience at Stanford University Medical Center during the years 1965-1986. There were 240 children 15 years of age or younger, 92 girls and 148 boys; with median follow-up of 9 years, maximum follow-up was 26 years. Of this cohort, data on gonadal function were available on 20 boys, 5 of whom were considered prepubescent; they had no clinical evidence of sexual maturation and were less than 13 years of age. Evaluation of the boys included testicular biopsy, semen analyses and the ability to procreate. Serum gonadotropin hormone levels (FSH, LH) were studied in 11 boys who also had semen analyses. Sexual maturation was attained in all boys without the need for androgen replacement. Among the eight boys treated with radiation alone, four were able to father a child (3 following 40-45 Gy pelvic radiation dose, 1 without pelvic radiation) from 3-19 years following treatment. Three others who received 30-44 Gy pelvic radiation were oligospermic when tested at 10 to 15 years post-treatment. Semen analyses in 10 of 12 (83%) boys who had been treated with six cycles of MOPP with or without pelvic radiation revealed absolute azoospermia with no evidence of recovery as along as 11 years of follow up. Following prolonged azoospermia, 2 of the 12 boys (17%) had recovery of fertility, with normalization of sperm count and/or ability to procreate at 12 and 15 years following treatment. There was no correlation with serum gonadotropin levels and sterility. Data on menstrual history, pregnancy and offspring were available in 86 (92%) of the girls. Seventy-five of the 86 girls (87%) have normal menstrual function. However, none of the females who underwent pelvic radiation without prior oophoropexy has maintained ovarian function. Both the prepubescent and postpubescent boys were affected by 6 cycles of MOPP whether or not pelvic radiation was administered. On the other hand, in girls similarly treated, ovarian injury was directly related to both the number of cycles of chemotherapy and the ovarian radiation dose. The chances of maintaining gonadal function following combined modality treatment are significantly greater among girls than boys. The progeny of patients treated for Hodgkin's disease appear normal and no excess fetal wastage has been noted. PMID- 2211256 TI - Comparison of two total body irradiation regimens in allogeneic bone marrow transplantation for acute non-lymphoblastic leukemia in first remission. AB - Between November 1976 and December 1987, 84 patients with newly diagnosed acute non-lymphoblastic leukemia who had achieved complete remission underwent non T cell depleted allogeneic bone marrow transplantation from Human Leukocyte Antigen Mixed Lymphocyte Culture (HLA-MLC) matched sibling donors. The first 36 patients (November 1976-June 1983) were prepared with cyclophosphamide, 60 mg/kg/day, IV for 2 days and single fraction total body irradiation with 750 cGy at a dose rate of 26 cGy/minute (Group I). The next 48 patients (July 1983-December 1987) were prepared with similar chemotherapy, but received hyperfractionated total body irradiation with total 1320 cGy, 165 cGy twice a day at a dose rate of 10 cGy/minute (Group II). Patient characteristics between these two groups are similar except for the significantly older age distribution in Group II. Median follow-up of Groups I and II are 8 years and 11 months and 2 years and 3 months, respectively. The Kaplan-Meier relapse-free survival, survival, and relapse rates at 3 years are 56, 58, and 19% in Group I and 69 (p = 0.22), 77 (p = 0.07), and 10% (p = 0.37) in Group II. There is no difference in the incidence of interstitial pneumonitis, viral or idiopathic, engraftment rate, or incidence of graft versus host disease (GVHD) between these two groups. The fractionated total body irradiation treated group had significantly less nausea and vomiting. Multivariate analysis shows that total body irradiation regimen is not a significant factor in regard to relapse rate, relapse-free survival, and survival. PMID- 2211257 TI - Preoperative irradiation for soft tissue sarcomas of the trunk and extremities in adults. AB - Between May 1978 and January 1987, 58 adult patients with previously untreated sarcomas of the trunk and extremities were treated with preoperative irradiation and surgery at the University of Florida. All patients had a minimum of 2 years of follow-up; 24 had a minimum of 5 years of follow-up. The preoperative dose was usually 5040 cGy, with 120-125 cGy per fraction delivered twice daily. Operations were performed 2 to 6 weeks after radiation therapy. Eight patients received adjuvant chemotherapy. The tumors were high grade in 52 (90%), measured greater than 10 cm in 45 (78%), and were extracompartmental in 49 (84%). The surgical margins were wide in 17, marginal in 31, and intralesional in 10 patients. A functional extremity was preserved in 47 of 54 patients who would have required an amputation had they been treated by operation alone. Five of 58 patients (9%) developed local failure; in three, the failure occurred outside of the irradiated volume. Survival rates (product-limit method) at 5 years according to grade and size of lesion were as follows: low grade, 100%; high grade, 10 cm or less in largest diameter, 68%; high grade, 11-20 cm, 39%. Data are insufficient for a 5 year analysis of high-grade lesions greater than 20 cm; to date, there are no 5 year survivors in these patients. Moderate and severe wound complications occurred in 16%. There were four pathological fractures in 52 long bones at risk. PMID- 2211258 TI - Postoperative radiotherapy in the treatment of extremity soft tissue sarcomas. AB - From 1966 to 1983, 50 patients with extremity soft tissue sarcomas were treated with wide local excision and postoperative radiotherapy at the Mallinckrodt Institute of Radiology. The median follow-up was 70 months (range 28 to 168). Grade was the most significant factor affecting survival: all 11 patients with well differentiated tumor survived versus 6/8 patients with moderate and 17/31 patients with poorly differentiated tumors (p less than 0.01). In addition, lymph node involvement at diagnosis conferred a worse prognosis with only 2/5 patients alive after treatment (p less than 0.05). Eleven of 50 (22%) failed locally. Factors affecting local control included gross residual tumor after operation and limited treatment volume. Among the 35 patients who did not have gross residual tumor or limited treatment volume, two patients who received less than 5000 cGy failed locally versus 1/18 patients who received between 5000-6000 cGy and 2/15 patients who received more than 6000 cGy. Microscopically positive margins and a volume encompassing less than the total muscular compartment was not associated with an increase in the incidence of local failure. Eight patients developed local complication: five due to retreatment for local recurrence. Overall, 24/26 patients who are alive have had their limbs preserved with normal function. PMID- 2211259 TI - Limb salvage in soft tissue sarcomas involving neurovascular structures using combined surgical resection and brachytherapy. AB - While there is debate in the literature concerning the tolerance of neurovascular structures to external beam radiation, the tolerance of these tissues to interstitial radiation has never been established. To evaluate the dose of radiation and its effect on early and late toxicity of neurovascular structures, a retrospective review of our experience was undertaken. Between 1975 and 1987, 299 patients with extremity sarcomas underwent limb-sparing surgery and tumor bed Iridium-192 interstitial implantation at Memorial Sloan-Kettering Cancer Center. Forty-five patients (15%) of this group were found to have locally advanced tumors involving major neurovascular structures. Of these patients, 64% had high grade lesions. Eleven percent had evidence of gross residual disease on these structures, and an additional 58% had microscopic residual disease at or close to the margins of resection. After loading catheters were placed directly upon the neurovascular structures in the exposed tumor bed and a median dose of 4400 cGy was delivered to the target volume. Eight patients had previous radiation to the treated field and 13 patients received postoperative radiation. With a median follow-up of 4 years, the 5-year actuarial disease-free survival was 69% and the 5-year actuarial freedom from in-field failure was 79%. The 5-year actuarial incidence of distant metastases was 30%. Eighty-four percent of the patients maintained long-term preservation of limb function without the need for amputation. Four patients (9%) ultimately developed evidence of radiation neuritis 6-20 months post therapy. All four patients had received additional radiation with cumulative doses exceeding 9000 cGy to the neurovascular bundle. We conclude that combined surgical resection and interstitial radiation for locally advanced sarcomas with neurovascular involvement can provide excellent local control with preservation of limb and neurovascular function without significant toxicity. PMID- 2211261 TI - Nasopharyngeal carcinoma: orderly neck node spread. AB - A prospective study of 271 consecutive patients with newly diagnosed nasopharyngeal carcinoma was undertaken to assess the pattern of cervical nodal involvement with reference to 10 cervical nodal groups and three levels of neck; 204 (75.3%) patients were found to have cervical lymphadenopathy at presentation. Fifty-four (26.5%) of these patients had right cervical lymphadenopathy, 70 (34.3%) had left cervical lymphadenopathy, and 80 (39.2%) had bilateral cervical lymphadenopathy. The occurrence of lymphadenopathy in the 10 cervical nodal groups and the mean size of nodes in these nodal groups were computed. The subdigastric and upper jugular group was involved in more than 95% of cases. The lower the position in the neck, the less frequently the nodal group was involved. The mean size of nodes was largest in the subdigastric and upper jugular region compared with the other groups. The nodes in the upper neck were generally larger than those in the lower neck. The lower two levels of neck were involved without involvement of the upper level of the ipsilateral neck in fewer than 4% of cases. The present study indicates that neck node involvement by nasopharyngeal carcinoma is by orderly spread down the neck, which explains the adverse prognostic significance of neck node involvement in the lower neck. The orderly involvement of the neck nodes suggests that prophylactic irradiation of the neck should be given at least one level beyond the clinical extent of disease, which for patients with no clinically palpable node would mean prophylactic irradiation of the upper neck. PMID- 2211260 TI - Cervical metastases from unknown primaries: radiotherapeutic management and appearance of subsequent primaries. AB - Between 1964 and 1986, 72 patients who presented with squamous or undifferentiated metastatic carcinoma to neck nodes, where the primary tumor could not be found by standard clinical procedures, were treated at the Mallinckrodt Institute of Radiology. These cases were managed in the following manner: biopsy and radiotherapy in 46 out of 72 patients, radiotherapy (RT) and a planned neck dissection in 14 out of 72, and neck dissection after failure to achieve a complete response (CR) with RT in 12 out of 72. Minimum follow-up was 2 years. The initial CR rates for stages N1, N2a, N2b, N3a, and N3b were 83%, 93%, 61%, 50%, and 33%, respectively. The long-term neck tumor control for the same stages was 83%, 71%, 67%, 44%, and 50%, respectively. One patient had soft tissue necrosis and two had carotid artery ruptures, one of which left no symptomatic sequelae. Twenty-one out of 72 patients developed subsequent primary tumor. Only one of these patients survived. This incidence was not affected significantly by prophylactic treatment of the mucosal areas except in patients with bilateral neck nodes, undifferentiated or poorly differentiated histologies, and/or posterior cervical node involvement. A multivariate analysis showed that prognosticators of an improved disease-free survival were: a complete clearance of tumor by the end of radiotherapy (p less than 0.0009) and no appearance of a subsequent primary tumor (p = 0.035). The only factor that correlated with an increased loco-regional control was having a complete response by the end of radiotherapy (p less than 0.00009). The recommended management and possible ways of preventing the appearance of subsequent primaries will be discussed. PMID- 2211262 TI - Radiation myelopathy in primates treated with conventional fractionation. AB - A rhesus monkey model was used to assay the radiation tolerance of the spinal cord to 60Co radiation given in 2.2 Gy fractions. The D50 was found to be 76.1 Gy (SEM = 1.9 Gy); the estimated doses for 1% and 0.1% myelopathy were 59.1 +/- 5.5 Gy and 52.1 +/- 7.1 Gy, respectively. The latent period ranged from 5 to 20 months and decreased with increasing dose. All symptomatic animals had white matter parenchymal lesions involving major motor tracts, and most also had vascular lesions in the white matter. Spinal cords of asymptomatic animals had either no histopathologic changes or small white-matter lesions that did not involve motor tracts. PMID- 2211263 TI - Influence of scheduling, dose, and volume of administration of a perfluorochemical emulsion on tumor response to radiation therapy. AB - Studies were carried out with a new, concentrated perfluorochemical emulsion (PFCE) of the perfluorochemical F44E (48% V/V). When given at 4, 1.6, or 1 g/kg in undiluted injection volumes iv 1 hr prior to a range of single doses of radiation with inspired carbogen dose modifying factors (DMF's) based on tumor growth delay (TGD) in the Lewis lung tumor of 2.5, 1.7, and 1.5, respectively, were produced. When the PFC dose was administered in a volume of 0.2 ml, the dose modifying factors produced by 4 g/kg (0.1 ml undiluted) did not change significantly (2.6), but the dose modifying factors produced by 1.6 g/kg (0.04 ml undiluted) and by 1.0 g/kg (0.025 ml undiluted) increased significantly to 2.0 and 1.8 (p less than 0.05), respectively. Using the tumor excision assay at 24 hr post treatment in the FSaIIC fibrosarcoma, administration of 6, 4, or 2 g/kg in 0.2 ml injections plus carbogen breathing 1 hr prior to and during treatment resulted in dose modifying factors of 1.5, 1.6, and 1.3, respectively. In a fractionated radiation protocol in the Lewis lung tumor using four daily fractions, a dose of 4 g/kg of PFC on days 1 and 3 proved superior to a dose of 2 g/kg daily (dose modifying factors 2.4 vs. 1.9, p less than 0.05). When a fractionated radiation regimen of 3 Gy daily X 5 and carbogen was used, PFC doses of 0.5, 1, 2, and 4 g/kg administered undiluted produced increasing tumor growth delays with increasing dose of PFCE and increasing frequency of administration. In addition, dilutions to 0.2 ml proved significantly more effective. In a 2-week fractionated radiation protocol using 2, 3, or 4 Gy daily X 5 weekly, PFCE given in 0.2 ml volume plus carbogen breathing daily at 4, 1.6, or 1 g/kg produced dose modifying factors of 2.0, 1.9, and 1.6, respectively. Finally, when used in a day 1, 3, and 5 radiation regimen for 3 weeks at 2, 3, or 4 Gy/fraction, 4 g/kg of PFCE given in a volume of 0.2 ml plus carbogen breathing produced a superior dose modifying factor (1.6) as compared with 1.6 or 1.0 g/kg (dose modifying factors 1.4 and 1.3, respectively). These results indicate that PFCE plus carbogen breathing effectively enhances the antitumor effects of both single dose and fractionated radiation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2211264 TI - Tumor tissue oxygenation as evaluated by computerized-pO2-histography. AB - A computerized pO2 measurement system with a novel electrode motion pattern (Sigma-pO2-histography) was evaluated in vitro and in vivo. The system was found to be reliable in 0.9% saline and 10% hydroxyethylene starch solution and in fresh donor blood. Marked deviations were found in lipid and hemoglobin solutions and in fluorocarbon emulsions. Histograms obtained in rat liver, mouse muscle, and subcutis were similar to previously reported distributions. Direct comparison between Sigma-Eppendorf and self-constructed Whalen-type electrodes in hypoxic tumors gave similar results. A large series of measurements indicated that hypoxic and anoxic tissue areas were frequently found both in isografted rodent and in xenografted human tumors. The extent of oxygen deprivation depended on the cell line studied, tumor size, implantation site, the vascularity, and the actual tissue perfusion. Pentobarbital anesthesia redistributed the tumor oxygenation without affecting the median pO2 value. Tumors growing in a pre-irradiated bed were less oxygenated than those at untreated sites. Hyperthermia at therapeutically relevant temperatures reduced pO2 levels in adequately oxygenated tumors whereas little change was detected in poorly oxygenated tumors. First measurements in tumors in patients revealed marked inter- and intratumor heterogeneity. It is concluded that this novel technique is suitable for routine measurements of tissue oxygenation of solid tumors in situ. PMID- 2211265 TI - In vitro effect of doxorubicin on non-proliferating and proliferating epithelial cells. AB - In vitro cultured mouse kidney epithelial cells were exposed for 2 hr to 0.5 microgram/ml of Doxorubicin. The proliferative activity of the cells was determined by combined DNA and total nuclear protein measurements. The sensitivity of the cells to the drug was higher in proliferating cells as compared to non-proliferating ones, that is, those exhibiting low amounts of total nuclear protein per unit DNA. PMID- 2211266 TI - Randomized study of 5 fluorouracil and cis platin as neoadjuvant therapy in head and neck cancer: a preliminary report. AB - A randomized prospective study of 5 fluorouracil (5-FU) and Cis platin preceding definitive local treatment for squamous cell carcinoma of the head and neck region was initiated in September 1986. Seventy-five patients were stratified by site (oral cavity-12, oropharynx-28, larynx-16, hypopharynx-19), and by Stage (Stage II-20, Stage III-43, Stage IV-12) and randomized to receive definitive local treatment (surgery and post-operative radiation or radiation alone) or chemotherapy followed by definitive local treatment. Chemotherapy consisted of three cycles of 120 hr 5-FU infusion 1 g/m2/day plus Cis platin 100 mg/m2 on day 1 on each cycle. Response to chemotherapy was complete in 17 patients (46%) for an overall response rate of 68%. All the patients have completed therapy with a median follow-up of more than 12 months. After local treatment, the complete response rate is 84% for the control group and 86% in the chemotherapy group. Actuarial disease-free survival at 1 year is 61% in the control group and 73% in the chemotherapy group (p = 0.25). These preliminary results show that in spite of initial tumor response, neoadjuvant chemotherapy does not improve long-term control and survival. PMID- 2211267 TI - Masses of myeloadipose tissue: radiological and clinical considerations. AB - The records of 30 patients presenting radiological evidence of masses of extramedullary myeloadipose (hemopoietic) tissue, 25 patients suffering from thalassemia, one from sickle-cell anemia, and one from myelofibrosis were studied. Three patients presented with primary myelolipomas. Most of the patients with thalassemia presented with masses of hemopoiesis in the costovertebral angle and five patients presented with spinal cord compression. Magnetic resonance imaging is the best method for visualization and assessment of the extent of the masses in the thorax and spinal canal. Radiotherapy is the treatment of choice for spinal cord compression. One patient with thalassemia and one patient with myelofibrosis presented with masses of extramedullary hemopoiesis in the adrenals. All five patients with masses of myeloadipose tissue in the adrenals were treated surgically. PMID- 2211268 TI - Local-regional non-rhabdomyosarcomatous soft tissue sarcomas of the head and neck. AB - Between 1962 and 1987, 112 consecutive patients were treated at St. Jude Children's Research Hospital for soft tissue sarcomas of the head and neck region; 18 of these children (16%) had histologic subtypes other than rhabdomyosarcoma. We evaluated the impact of surgery, postoperative chemotherapy, and irradiation on local control and survival in these cases. Three patients who had complete resection of tumors and received no further treatment are alive without disease at 36, 42, and 162 months. Local control was achieved in 1 of 2 patients with microscopic residual tumor and 4 of 9 patients with gross residual tumor who were treated with irradiation (2500-5040 cGy). Chemotherapy was the only postoperative treatment in three patients; only one achieved lasting local control. One patient was treated with irradiation only; his primary site showed no tumor cells at autopsy following an automobile accident. Overall, local control was achieved in 50% of patients; the disease-free survival rate at 3 years was 44%. The prognosis for patients with nonresectable tumors remains unsatisfactory because of the difficulty in securing local control. A revised therapeutic approach to these patients is presented. PMID- 2211269 TI - Preseason cardiovascular examination: a review. AB - The responsibility of the physician performing a preseason sports physical examination includes identifying cardiac disease and giving appropriate guidance about participation in competitive sports. This article reviews the leading causes of sudden cardiac death in young athletes, discusses other common cardiac conditions, assesses recommendations for competitive sports, and discusses the preseason examination as a mechanism for detecting a cardiac problem that should exclude an athlete from competition. PMID- 2211271 TI - Financing health care for adolescents: problems, prospects, and proposals. AB - Currently, one in every seven adolescents, aged 10-18, is uninsured. This translates to nearly 5 million uninsured adolescents nationwide. Uninsured adolescents, as opposed to insured adolescents, are more likely to be members of poor and minority families. In addition, adolescents without health insurance use fewer health services than their insured counterparts even after controlling for health status differences. Improving the health insurance status of adolescents is becoming an important public policy objective, although Congress recently rejected legislation that would have expanded Medicaid coverage for poor adolescents. Despite this setback, legislators and child health associates are increasingly striving for public and private insurance expansions for adolescents. These efforts are described, and the prospects for future improvements in health insurance coverage of adolescents are discussed. PMID- 2211270 TI - Public policy issues affecting the health care delivery system of adolescents. AB - Policymakers are at an important crossroad in pursuing viable solutions to the dilemma of preventing and treating adolescent health problems. A variety of coordinated and comprehensive approaches will be needed to resolve these complex and often entrenched problems. In the absence of a national policy for children and youth, it is important that those concerned with these issues join efforts at the community, local, state, and national levels to move the policy agenda forward. As an interim step, it is necessary to work on building and evaluating model programs that will influence the development of new policy directions. Both efforts are needed to address the complex array of problems facing adolescents today. The future of adolescent health will be determined by a variety of factors, including public policy. Of particular importance in shaping public policy are four factors: (1) the American character, including ideas and attitudes that are the basis of politics and policy; (2) the pluralism that characterizes the process, including the relationship between government and the private sector and the dominant role of the private sector; (3) the federal system that distributes authority among various levels of government (federalism); and (4) incrementalism, which is the step-by-step process that characterizes the development of policies. Of particular importance in terms of adolescent health are the ideas and attitudes about adolescence and adolescents; the basic ideas that affect policies broadly; and the concepts of federalism, pluralism, and the role of the private sector in dealing with domestic social issues. Although the field of adolescent health continues to advance, many complex problems that have their origin in biological, behavioral, and sociocultural factors remain. Of particular importance are problems associated with lower socioeconomic status. The problems will not yield to the single-issue, categorical approach of the past but will require comprehensive strategies involving the health, education, income maintenance, job training, employment, and social service sectors. Public policies must support these integrated, coordinated approaches, and health providers concerned with adolescent health can and must play a vital role in this process. PMID- 2211273 TI - Skateboard injuries in children and adolescents. AB - Data from the Consumer Product Safety Commission show an increase in skateboard injuries since 1984. This study analyzed reports of injuries in children and adolescents who use skateboards and the use of protective clothing by skateboard users. A convenience sample of 94 users, aged 6-18 years, in a metropolitan HMO was evaluated by questionnaire. Significant injuries associated with skateboard use (lacerations, unconsciousness, fractures, or other) were reported by 13% of the subjects. Frequency of skateboard use was strongly associated (p less than 0.01) with significant injury. Use of protective clothing was not associated with a lower proportion of injured users. Older adolescents reported a higher proportion of injuries than younger adolescents or children did. These findings suggest a high injury prevalence among skateboard users. Prevention strategies should be critically evaluated and should not rely solely on the use of protective clothing. PMID- 2211272 TI - Premenarcheal predictors of the experience of menarche: a prospective study. AB - The goals of this study were (1) to assess, with a prospective design, the impact of premenarcheal menstrual attitudes and personality attributes for menarcheal experience and (2) to assess the relative strength of these variables, in relation to menarcheal timing and preparation for menarche, for predicting menarcheal experience. The subjects were 92 girls, who changed from pre- to postmenarcheal between two test occasions, 6 months apart. When premenarcheal menstrual attitudes and personality attributes were examined independently, results revealed that affirmation, a menstrual attitude, and depression significantly predicted emotional response to menarche. When these two variables were examined, together with preparation and timing variables, the two significant predictors of menarcheal experience were preparation and affirmation. The results provide direction for, and optimism about, the potential efficacy of menstrual education in promoting more positive menarcheal experience. PMID- 2211274 TI - Multifactorial causes of adolescent driver accidents: investigation of time as a major variable. AB - This study examined all reported motor vehicle accidents with adolescent drivers, aged 18 and under, in Wichita, Kansas, during 1987. The analysis focused on several time variables that may influence the cause of an accident, including time of day, day of week, and school versus nonschool day. Data analysis from 1903 accident reports showed a predominance of accidents among male drivers, a higher accident prevalence on school days, and a cluster of accidents on school days before school, during lunch hours, and immediately after school. Accidents on weekends and nonschool days clustered later in the day, with alcohol-related and injury accidents occurring more frequently than on school days. These results have potential implications for health care professionals working with youths on health promotion/disease prevention, for policymakers who schedule school activities, and for those involved in driver safety and education. PMID- 2211276 TI - Maternal age, sociodemographics, prenatal health and behavior: influences on neonatal risk status. AB - The effects on neonatal outcome of maternal age, sociodemographic status, and prenatal health and behavior were assessed in a representative national sample of youth (National Longitudinal Survey of Work Experience of Youth). Primiparous women were categorized into four age-at-birth groups: 13 to 15 year old, 16 to 18 year old, 19 to 21 year old, and 22 to 30 year old. Younger mothers were lighter, gained less weight during pregnancy, and sought prenatal care later in their pregnancy. Neonates of the youngest mothers on average had lower birth weights, and shorter gestation periods. There were significant effects of maternal age, race, education, and pregnancy weight gain on the probability of giving birth to a premature or low-birth-weight infant. Our results also implicated the time of first prenatal care in the occurrence of premature delivery. We believe that interventions should emphasize the prevention of pregnancy in young adolescents and amelioration of the adverse prenatal conditions associated with living in lower socioeconomic conditions. PMID- 2211275 TI - Nausea and vomiting during teenage pregnancy: effects on birth weight. AB - Early pregnancy nausea and vomiting (NVP) has been reported to be a favorable risk factor for pregnancy outcome. We studied nausea and vomiting in 239 randomly selected teens from a geographic-based cohort of nearly 2800 pregnant adolescents from Camden County, New Jersey. Early (first trimester) NVP was reported by 20.9%, and an additional 17.6% reported that their NVP persisted into the second or third trimester (late NVP). After adjusting for confounding factors (length of gestation, maternal age, ethnicity, prepregnant body mass index, weight gain, and smoking), we found that early NVP alone did not significantly affect birth weight. Late NVP, however, was associated with a significant decrement in birth weight (-256.5 +/- 108.0 g, p less than 0.05). Further, the effect of late NVP was greater when maternal weight gain was inadequate. Teenagers with continued NVP are more likely to be nutritionally stressed during the course of their pregnancy. PMID- 2211277 TI - Subfecundity: a prenatal risk factor for adults but not for adolescents. AB - Young maternal age is associated with an increased incidence of low birth weight and prematurity; controlling for sociodemographic factors reduces the significance of this relationship. We hypothesized that this is partly because in a sociodemographically homogeneous population the adverse effects of maternal subfecundity on fetal growth confound the relationship between maternal age and infant outcome. To test this hypothesis, we studied the reproductive histories of 90 adolescent (less than 20 years old) and 35 adult lower socioeconomic, black prenatal patients. We found a strong, positive relationship between maternal age at conception and duration of unprotected intercourse prior to conception (r = 0.40; p less than 0.0001). Adults reporting 2 or more years of unprotected intercourse prior to conception were at highest risk for low birth weight (p = 0.02). Our findings demonstrate that it is important that adult controls for adolescent pregnancy studies have voluntarily postponed conception. PMID- 2211278 TI - Prenatal education outcomes for pregnant adolescents and their infants using trained volunteers. AB - This study evaluated the effects of lessons taught by trained nonprofessional volunteers in community prenatal clinics. Project participants (n = 210) and comparison subjects (n = 189) were pregnant women, aged 18 years or younger. Participants were divided according to those who attended eight or more lessons (high treatment, n = 94) and those who attended fewer lessons (n = 116). A system of rewards for attendance was used. The number of prenatal visits was significantly different between the three groups (p less than 0.001), with the high-treatment participants having a significantly greater number of visits than the other groups. The groups differed on gestational age at delivery (p less than 0.006), favoring the infants of high-treatment participants; however, only 8% of gestational age variance was attributable to prenatal visits. A significantly greater proportion of high-treatment participants returned for postpartum care (p less than 0.011 vs. low-treatment participants, p less than 0.002 vs. comparison subjects). Postpartum return was not improved by a hospital visit by a volunteer. Regardless of treatment, most (99%) accepted a contraceptive method at their postpartum visit. The groups did not differ on their return for method check at 3 months. However, a significantly greater proportion of the high-treatment participants returned for an annual family planning evaluation (p less than 0.015 vs. low-treatment participants, p less than 0.005 vs. comparison subjects). Both the high- and low-treatment participants differed significantly from the comparison subjects on having taken their infants for at least one well-child visit during the first year (p less than 0.001 for both tests).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2211279 TI - Incentives and their influence on appointment compliance in a teenage family planning clinic. AB - The purpose of this study was to ascertain whether or not the family-planning compliance patterns of indigent adolescents could be influenced by various types of incentives. From February 1988 through January 1989, 534 postpartum inner city teenagers, aged 12-19, who delivered at a large city-county public hospital, participated. Teens were randomly assigned to two treatment groups that either offered a coupon for milk for the infant or a gift for the teenage mother if they returned for their postpartum visit 4-6 weeks after delivery. A third group, which used no incentive for appointment keeping, acted as a control. Although overall compliance was low, a significant relationship was found between type of program incentive and compliance outcome. The program using milk coupons as an incentive had the best compliance rate. This incentive appeared to be most effective with black adolescents. Such incentive programs, although not without controversy, offer a potential way to enhance postpartum contraceptive appointment-keeping compliance in a high-risk population. PMID- 2211280 TI - History of sexual abuse in incarcerated adolescents with gonorrhea or syphilis. AB - From July 1983 to June 1984, 2521 adolescents were medically screened at entry into a detention facility in New York City. A medical history, physical examination, serology for syphilis, and culture for gonorrhea were obtained from each entrant. A retrospective chart review was conducted for 136 persons with gonorrhea and/or syphilis (79 boys and 57 girls) and 136 sex-matched infection negative controls. Several characteristics were compared including age, age at first sexual intercourse, sexual abuse history, contraceptive use, and pregnancy status. Among infected cases, 8% of males and 32% of females reported a history of sexual abuse, whereas among controls, no males and 14% of females reported abuse. A history of sexual abuse was strongly associated with gonorrhea or syphilis (odds ratio = 3.4; 95% confidence intervals, 1.5-8.0). These data suggest an association between sexual abuse and subsequent high-risk sexual behavior manifested by a gonorrhea or syphilis infection. PMID- 2211282 TI - Menu options. PMID- 2211281 TI - Life-threatening desmoid tumor. AB - An 18-year-old girl presented with severe chest pain and shortness of breath. She was found to have a large desmoid tumor filling the right chest cavity. The etiology of the desmoid tumor is unknown but is thought to be associated with an underlying genetic defect and local trauma. These tumors may be estrogen sensitive and are more frequent in females of reproductive age. The case demonstrates the difficulty in treating these tumors effectively. PMID- 2211284 TI - Pneumonia only in parenchymatous lungs. PMID- 2211283 TI - Comments on bovine spongiform encephalopathy. PMID- 2211285 TI - Encourages new services to replace tube deworming. PMID- 2211286 TI - Dual degrees equip veterinarians for novel careers. PMID- 2211287 TI - Scrapie: minor disease, potentially major problem. PMID- 2211288 TI - Endotoxin as an alarm signal of bacterial invasion: current evidence and implications. PMID- 2211289 TI - We must take a stand on controversial issues. PMID- 2211290 TI - Client retention. PMID- 2211291 TI - Efficacy of intramammary treatment in unbred and primigravid dairy heifers. AB - A total of 73 breeding-age and primigravid Jersey heifers in 4 herds was randomly allotted to treatment and control groups according to expected calving date. Thirty-five heifers were injected intramammarily with a nonlactating cow product containing penicillin/streptomycin. Thirty-eight heifers served as untreated controls. Of the 35 treated heifers, 34 (97.1%) were infected at time of treatment. In the untreated control group, all 38 heifers (100%) were infected at treatment time. At parturition, prevalence of intramammary infection in treated heifers decreased to 40%, whereas in the control group, prevalence remained about the same (97.4% of heifers). Prevalence of Staphylococcus aureus mastitis in treated heifers was reduced from 17.1% to 2.9% after treatment. In the control group, prevalence of S aureus mastitis decreased from 26.3% to 15.8%. Heifers treated during the second trimester of pregnancy had the greatest reduction in prevalence of mastitis and in somatic cell count at parturition, compared with controls. Findings indicated that intramammary treatment during pregnancy in primigravid heifers was effective in reducing prevalence of mastitis and somatic cell counts at parturition. PMID- 2211292 TI - Trichinosis in a dog. AB - Trichinella spiralis infection was identified by direct fecal examination as the cause of gastrointestinal disease in a dog. The source of infection was believed to be a woodchuck. Management included supportive care and benzimidazole treatment. Vomiting, diarrhea, anorexia, and myalgia are the main signs of trichinosis, but routine fecal examination seldom reveals T spiralis in natural infections. Mebendazole is the recommended anthelmintic and should be used to eliminate intestinal larvae and prevent muscle invasion. Although the prevalence of trichinosis is decreasing in swine, wild mammals may still be a potential source for dogs and cats. Nevertheless, because of the nonspecific clinical signs of trichinosis, many cases probably go undiagnosed. PMID- 2211293 TI - Familial renal amyloidosis in Chinese Shar Pei dogs. AB - Renal amyloidosis was diagnosed in 14 young Chinese Shar Pei dogs, all of which were related. Clinical signs were those of renal failure and included vomiting, anorexia, lethargy, polydipsia, polyuria, weight loss, and dehydration. Some dogs had a history of intermittent fever and joint swelling. Laboratory findings also were compatible with renal failure and included azotemia, hyperphosphatemia, low total CO2 content in serum, isosthenuria, proteinuria, and hypercholesterolemia. All dogs had medullary deposition of amyloid, and 9 of 14 (64%) had glomerular involvement. The remaining renal lesions were typical of end-stage renal disease. In some dogs, amyloid deposits were found in other tissues (eg, liver, spleen, stomach, small intestine, myocardium, lymph node, prostate gland, thyroid gland, and pancreas). Amyloid deposits were sensitive to potassium permanganate oxidation, suggesting the presence of amyloid protein AA. PMID- 2211295 TI - Hip dysplasia with bilateral ischiatic nerve entrapment in a dog. AB - Dysfunction of both ischiatic nerves was detected in a 5-year-old spayed Labrador Retriever with radiographic evidence of severe bilateral hip dysplasia. Marked hyperflexion of the hip and stifle was evident when the dog walked. Results of electromyography confirmed the ischiatic nerve involvement. At staged operations, both ischiatic nerves were found to be compressed between the sacrotuberous ligament and proliferative tissue around the hip. One year after surgery, electromyographic and physical findings were essentially normal. PMID- 2211294 TI - Nasal adenocarcinoma metastatic to bone in two dogs. AB - Diagnosis of nasal adenocarcinoma was made in a 6-year-old 35-kg neutered Golden Retriever and a 6-year-old 8-kg spayed mixed-breed dog with chronic bilateral nasal discharge unresponsive to antibiotics. Treatment for the Golden Retriever consisted of bilateral rhinotomy, curettage, and postoperative fractionated 48-Gy orthovoltage irradiation. The mixed-breed dog was treated with cisplatin. After complete remission of the primary neoplasm, the dogs were reevaluated because of acute lameness. Radiography of the right stifle of the Golden Retriever revealed soft tissue swelling, extensive bony destruction of the distal femoral metaphysis and epiphysis, and pathologic fracture involving the medial condyle. Radiography of the left scapula of the mixed-breed dog revealed lysis of the glenoid cavity and subchondral scapular bone. Diagnosis of metastatic carcinoma was made in both dogs. With treatment improvements and longer survival time of affected dogs, sinonasal neoplasia may be observed to develop in similar life-threatening metastatic sites. PMID- 2211296 TI - Arthrodesis for congenital luxation of the shoulder in a dog. AB - Congenital luxation of the shoulder in a 7-month-old Chihuahua was corrected by use of arthrodesis. A single lag-screw fixation technique was used. Arthrodesis of the shoulder provides a favorable alternative to other salvage techniques such as glenohumeral resection or amputation. PMID- 2211297 TI - Vincristine sulfate as single-agent chemotherapy in a dog and a cat with malignant neoplasms. AB - A 12-year-old 4-kg spayed domestic shorthair cat with a poorly differentiated fibrosarcoma of the rostral aspect of the mandible and an 11-year-old 13-kg castrated dog of mixed breeding with pulmonary metastatic hemangiosarcoma were treated with 0.5 mg of vincristine sulfate/m2 of body surface, IV, weekly. Three months after beginning treatment, both animals had complete clinical remission. The role of this vinca alkaloid as a single agent for malignant neoplasms has seldom been discussed in the veterinary scientific literature. The results of these two cases indicate that single-agent vincristine sulfate chemotherapy is effective in the treatment of feline fibrosarcoma and canine hemangiosarcoma. PMID- 2211298 TI - Chylothorax associated with dirofilariasis in a cat. AB - A 4-year-old castrated domestic shorthair cat was referred for treatment of chylothorax. Thoracic duct lymphangiography revealed partial obstruction of the cranial vena cava, as evidenced by filling of mediastinal lymphatics with dye instead of all of the dye entering the vena cava. The thoracic duct was ligated via left 10th intercostal space thoracotomy. Immediate postligation lymphangiography revealed successful duct ligation. Results of a serum ELISA for adult heartworm antigen that was performed before surgery were positive. Drug treatment for the heartworm disease was not recommended, because the pleural effusion had ceased (as determined by radiographic examination 3.5 and 9 months after surgery) and the cat was doing well clinically. Sixteen months after surgery, the owner reported that the cat was doing well and did not have signs of respiratory problems. PMID- 2211299 TI - What is your diagnosis? Intraluminal filling defects of the urinary bladder as well as osteophytes on the ventral surface of the caudal lumbar and sacral vertebrae. PMID- 2211300 TI - Rehabilitation of wild animals. PMID- 2211301 TI - Equine euthanasia. PMID- 2211302 TI - Carrying professional pride into retirement. PMID- 2211303 TI - Veterinarians and credit cards--when the client reneges. PMID- 2211304 TI - Initiatives in clinical research. PMID- 2211305 TI - Lack of supportive susceptibility data for use of ampicillin together with trimethoprim-sulfonamide as broad-spectrum antimicrobial treatment of bacterial disease in dogs. AB - The combination of ampicillin together with trimethoprim-sulfonamide is sometimes used as a broad-spectrum antimicrobial regimen for treatment of dogs with bacterial infections of unknown etiopathogenesis. To determine whether this combination is indeed broad spectrum, we analyzed susceptibility data derived from commonly encountered bacterial agents in dogs. A total of 381 isolates from 344 cases was studied. Overall, 80 (20.9%) of the 381 isolates were resistant to ampicillin and to trimethoprim-sulfonamide; 159 (41.7%) were resistant to ampicillin, but susceptible to trimethoprim-sulfonamide; 131 (34.4%) were susceptible to both ampicillin and trimethoprim-sulfonamide; and 11 (2.9%) were susceptible to ampicillin, but resistant to trimethoprim-sulfonamide. Of isolates susceptible to ampicillin and/or trimethoprim-sulfonamide, 290 (96.3%) were susceptible to trimethoprim-sulfonamide (ampicillin increased the coverage by 3.7%). On the other hand, 142 (47.2%) were susceptible to ampicillin. In addition, with respect to agents most commonly encountered (members of the family Enterobacteriaceae and members of the genus Staphylococcus), combining ampicillin with trimethoprim-sulfonamide increased coverage by 2.2% over use of trimethoprim sulfonamide alone. We contend, therefore, that use of ampicillin together with trimethoprim-sulfonamide does not result in an acceptable broad-spectrum antimicrobial regimen for treatment of bacterial disease in dogs. PMID- 2211306 TI - Serum thyroid hormone concentrations in clinically normal dogs after administration of freshly reconstituted vs previously frozen and stored thyrotropin. AB - Concentrations of serum thyroxine (T4) and 3,3',5-triiodothyronine (T3) were determined in 7 clinically healthy adult dogs before and after administration of freshly reconstituted thyrotropin (TSH) and TSH that had been previously reconstituted and frozen for 1, 2, and 3 months. The 4 TSH response tests were performed at 30-day intervals by collecting blood samples for serum T4 and T3 determinations before and 4 and 6 hours after IV administration of TSH (0.1 U/kg of body weight). Baseline serum concentrations of T4 and T3 were similar at each of the 4 sample collection times over the 3-month period of the study. Mean serum concentrations of T4 and T3 increased significantly (P less than 0.01) over baseline values after administration of freshly reconstituted TSH or TSH that had been previously frozen for 1, 2, or 3 months. Significant difference was not found in the mean post-TSH serum T4 or T3 concentration after injection of freshly reconstituted TSH or TSH that had been previously frozen for 1, 2, or 3 months. In 2 of the 7 dogs, mild reactions--mild ataxia and weakness--were observed during the last of the series of TSH response tests (ie, after IV administration of TSH that had been previously frozen for 3 months). Results of this study suggest that for use in dogs, reconstituted TSH stored at -20 C maintains adequate biological activity for at least 3 months. The ability to store reconstituted TSH for a longer period than the recommended 48 hours represents an economic advantage, because it allows clinicians to perform more TSH response tests per vial of TSH. PMID- 2211307 TI - Chlamydial infection and perinatal mortality in a swine herd. AB - Chlamydia psittaci was believed responsible for an episode of high perinatal death loss in a swine herd in which 8.5 pigs per litter normally were weaned. In this episode, 18 sows produced 186 pigs, with 50 survivors. Chlamydia was found in tissue samples, and other bacterial or viral pathogens could not be identified. Chlamydia was diagnosed by isolation (ELISA), histologic examination using immunoperoxidase staining techniques, and electron microscopy. Previously, C psittaci has not been considered in the differential diagnosis of swine perinatal mortality. PMID- 2211308 TI - Bacterial epididymitis in two stallions. AB - Two stallions had unilateral bacterial epididymitis attributable to S zooepidemicus infection. Diagnosis was based on bacterial isolation, WBC in the semen, higher than normal blood fibrinogen concentration, and leukocytosis with regenerative left shift. One horse had high seminal pH. Ultrasonography of the involved epididymides revealed changes consistent with the appearance of abnormal accumulation of exudate in the tail of the epididymis. Treatment included unilateral orchiectomy and antibiotic administration. In stallion 1, the infection persisted despite treatment. Treatment result was not available for stallion 2. PMID- 2211309 TI - Dystocia attributable to a fetal monster resembling schistosomus reflexus in a donkey. AB - A schistosomus reflexus fetal monster was removed from a jenny via cesarean section. This type of anomaly is seen principally in ruminants and swine. Only 3 cases have been reported in Equidae. PMID- 2211310 TI - Surgical management of Rhodococcus equi metaphysitis in a foal. AB - A chronic Rhodococcus equi metaphysitis involving the distal growth plate of the left third metatarsal bone had induced a longstanding lameness in a young foal. Abnormal hematologic values included mild anemia, hyperfibrinogemia, mild leukocytosis, and neutrophilia. Radiography of the distal portion of MT3 revealed a radiolucent zone on the medial aspect of the growth plate, and small pieces of bone suggestive of sequestra. Treatment with erythromycin estolate and rifampin, aggressive surgical debridement, and cancellous bone grafting helped resolve the bone infection. PMID- 2211311 TI - Ethmoidal hematoma in nine horses. AB - Ethmoidal hematoma was diagnosed in 9 horses by results of physical examination, endoscopy, radiography, and histologic examination of tissues. The horses had stertorous breathing (n = 4) or intermittently sanguineous nasal discharge (n = 7). All horses underwent sinusotomy and extirpation of the lesion. At reexamination 15 to 104 months after surgery (mean, 61 months), 3 horses had recurrence of ethmoidal hematoma, and 1 horse had ethmoidal hematoma involving the contralateral ethmoturbinates. One of the horses with recurrence of ethmoidal hematoma also developed a contralateral lesion; both lesions recurred and additional surgeries were performed. PMID- 2211312 TI - Endoscopic diagnosis of unilateral ectopic ureter in a yearling filly. AB - Unilateral ectopic ureter was diagnosed by endoscopic examination in an 18-month old filly examined because of chronic urine dribbling. Intramuscular administration of azosulfamide discolored the urine and enhanced visualization of the ectopic ureter. Endoscopy proved valuable in determining that only one ureter entered the urinary bladder and in locating the ectopic ureter in the ventral portion of the vagina. PMID- 2211313 TI - Serum thyroxine concentrations following fixed-dose radioactive iodine treatment in hyperthyroid cats: 62 cases (1986-1989). AB - The medical records of 62 hyperthyroid cats treated with a fixed dose of 4 mCi of radioactive iodine (131I) were reviewed. In 60 cats, serum thyroxine concentrations were determined after treatment, allowing evaluation of treatment success. Eighty-four percent of the cats had normal serum thyroxine concentrations after treatment. Five of the 60 cats (8%) remained hyperthyroxinemic after treatment. Five cats (8%) were hypothyroxinemic when evaluated within 60 days of treatment. Three of these cats had normal serum thyroxine concentrations 6 months after treatment, and none had clinical signs of hypothyroidism. The administration of a fixed dose of 4 mCi of 131I was determined to be an effective treatment for feline hyperthyroidism. PMID- 2211314 TI - Nutritionally variant streptococci associated with corneal ulcers in horses: 35 cases (1982-1988). AB - Nutritionally variant streptococci (NVS) are nutritionally deficient viridans streptococci that require pyridoxal for growth. Although NVS are pathogenic in human beings, they have not been considered to be pathogenic in domestic animals. In 1982 and 1983, 24 isolates of NVS were recovered from horses with ulcerative keratitis. A retrospective study was done to determine the incidence of NVS in horses with corneal disease. The medical records of 249 horses (259 eyes) examined for clinical signs of corneal disease were reviewed. Nutritionally variant streptococci were isolated from approximately 13.5% of horses with ulcerative keratitis. PMID- 2211316 TI - What is your diagnosis? Geographic bone destruction and periosteal reaction in the distal metaphyseal portion of the radius. PMID- 2211315 TI - Lymphocytic leukemia and lymphosarcoma in a rabbit. AB - Lymphocytic leukemia and lymphosarcoma were diagnosed in a rabbit with lethargy, emaciation, and pallor. The diagnosis was made on the bases of results of hematologic analysis, cytologic evaluation of a bone marrow specimen, and histologic examination. The lymphosarcoma was identified to be of T-cell origin. Leukemia is rarely diagnosed in rabbits, although lymphosarcoma is fairly common in this species. PMID- 2211318 TI - An open letter to animal rights activists: let's get our priorities in perspective. PMID- 2211317 TI - Impedance cardiography. PMID- 2211319 TI - Thoracic percussion. PMID- 2211320 TI - The embarrassed veterinarian. PMID- 2211322 TI - Evaluation of systemic administration of gentamicin for treatment of coliform mastitis in cows. AB - Recovery of cows (n = 61) with mastitis caused by gram-negative bacteria and treated systemically with an antibiotic (gentamicin) to which the bacteria were susceptible in vitro, was compared with recovery of cows (n = 13) with similar infections treated with a systemically administered antibiotic (erythromycin) to which the bacteria were resistant in vitro or with recovery of cows (n = 12) not given an antibiotic systemically. In the first part of the study, cows were selected for treatment groups by use of a diagnostic scheme designed to predict whether the mastitis was caused by gram-negative or gram-positive bacteria. In the second part of the study, all cows were treated without systemic administration of an antibiotic. Significant difference was not observed in the outcome of the disease between cows given gentamicin and cows of the other 2 treatment groups at 24 hours or at 4 weeks after treatment. At 24 hours after initial treatment, 71.9% of cows treated with gentamicin, 92.3% of those treated with erythromycin, and 45.5% not treated systemically had improved appetite. At 4 weeks after initial treatment, of the cows treated with gentamicin, 11.5% died; in 32.8%, lactation ceased in the affected mammary gland; in 21.3%, lactation was decreased in the affected gland; and 34.4% returned to normal lactation and health. Of cows treated with erythromycin, none died; in 23%, lactation ceased in the affected mammary gland; in 23%, lactation decreased in the affected gland; and 54% returned to normal lactation and health.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2211321 TI - Evaluation of heartworm immunodiagnostic tests. AB - In this report, the use of appropriate statistical methods for the evaluation of heartworm immunodiagnostic tests is discussed. The evaluation of these tests is complicated by factors causing variation in sensitivity, specificity, accuracy, and predictive values of positive and negative test results. The primary sources of inconsistency are variation in the prevalence of heartworm infection among populations of dogs and the sensitivity of immunodiagnostic tests to various categories of heartworm infections (ie, patent, immune-mediated occult, unisex occult, and immature occult). Sample size (ie, number of dogs tested) affects the confidence limit values of sensitivity and specificity. At least 100 dogs should be used in each testing group (infected and uninfected) to generate values of sensitivity or specificity within reasonably narrow confidence limits. Use of more than 200 dogs in each testing group contributes little to further narrowing of confidence limits. The selection of appropriate statistical tests for comparison of tests or comparison of the sensitivity or specificity of a single diagnostic test to various categories of heartworm infections is critical. The McNemar paired chi 2 test is appropriate for comparison of diagnostic tests, but it must be done by use of duplicate sera from each animal. A chi 2 test of independence, or, in the case of a small sample size, the Fisher exact test, is appropriate for comparing the sensitivity or specificity of a single diagnostic test to various categories of heartworm infection. PMID- 2211323 TI - Variable locations of nutrient foramina of the proximal phalanx in forelimbs of Thoroughbreds. AB - Bilateral metacarpophalangeal radiographs of 100 Thoroughbreds were examined for visualization and location of the major nutrient foramen of the proximal phalanx. The foramina were located on the dorsal or palmar aspects of the cortex or were not visible radiographically. Of the 100 horses, 60 had the same pattern in both forefeet. In the remaining 40 horses, the left and right proximal phalangeal foramina were asymmetric. Of the 200 proximal phalangeal foramina (100 horses), 53 were on the dorsal aspect of the cortex and 101 were on the palmar aspect of the cortex; 46 were not visible radiographically. Significant effect of age or gender could not be determined. PMID- 2211324 TI - Prekallikrein deficiency in a family of Belgian horses. AB - A 7-year-old Belgian stallion hemorrhaged excessively after castration; the hemostatic mechanism was investigated. The horse had normal one-stage prothrombin time and markedly prolonged activated partial thromboplastin time (APTT). Results of intrinsic coagulation factor assays were all normal with the exception of prekallikrein activity, which was markedly reduced (less than 1% activity; value for control population, 63 to 150%). Two of this horse's full siblings, a brother and sister, had markedly prolonged APTT and low prekallikrein values (2.5% and less than 1%, respectively). The addition of plasma from a normal equine plasma pool corrected the prolonged APTT in the 3 Belgian sibling with low prekallikrein activity. Prekallikrein activity in 10 other closely related Belgian horses ranged between 12.5 and 64% (mean, 29.3%), compared with 63 to 150% (mean, 91%) in 10 mixed-breed horses. In the 3 Belgian siblings with low prekallikrein activity, the APTT approached normal after prolonged incubation (15 minutes) with the contact activator and in response to addition of an ellagic acid activator. The 3 Belgian siblings with low prekallikrein activity may be homozygous for prekallikrein deficiency, whereas the other close relatives may be heterozygous for the genetic defect. PMID- 2211325 TI - Surgical stapling for repair of a rectal tear in a horse. AB - A grade-4 rectal tear in a mare was successfully repaired per rectum, using a surgical stapling device. The mare had only minor postoperative complications. This technique has some advantages over previously described procedures, but should be reserved for use in selected cases. PMID- 2211326 TI - Vacuum phenomenon in the metatarsophalangeal joint of a horse. AB - Vacuum phenomenon was induced inadvertently during radiographic examination of a metatarsophalangeal joint of a lame horse. The phenomenon was recreated in a sound horse when a metacarpophalangeal joint was radiographed in a stress-flexed position. Distraction of apposing articular surfaces may induce the vacuum phenomenon, which could result in misdiagnosis of an osteochondral defect or fracture. PMID- 2211327 TI - Subcutaneous part of the masseteric ramus of the external carotid artery as a proposed site of pulse-taking in Thoroughbreds. AB - The subcutaneous part of the masseteric ramus of the external carotid artery can be used as a proposed site of pulse-taking in most Thoroughbreds. It is located on the lateral surface of the masseter muscle, and its contour may be visible in association with a summer coat. PMID- 2211328 TI - Echocardiographic detection of an intact aneurysm in a horse. AB - Two-dimensional real-time echocardiographic examination of a 3-year-old Thoroughbred gelding with pleuropneumonia revealed an intact aneurysm of the right sinus of Valsalva, which was confirmed at postmortem examination. The horse had no clinical signs associated with the aneurysm. PMID- 2211330 TI - Partial uterine prolapse associated with uterine foreign body in a cow. AB - After correction of partial uterine prolapse in a Holstein cow, a 6-cm-long twig was found deep in the affected uterine horn. The twig was removed, and calcium dextrose and penicillin G were administered. Recovery was unremarkable. Other reports of uterine foreign bodies in cows are scarce and do not describe uterine foreign bodies associated with uterine prolapse or invagination. PMID- 2211329 TI - Malignant melanoma in the foot of a horse. AB - A 24-year-old horse had a malignant melanoma of the right forefoot. Because surgical excision of the melanoma was incomplete, as determined by histologic examination of the excised tissue margins, the tumor margins were injected with a matrix therapeutic implant containing cis-diamminedichloroplatinum, epinephrine, and purified bovine collagen matrix. The foot healed and the horse remained clinically free of disease for 26 months before recurrence of malignant melanoma. Surgical exploration of the digit revealed extensive involvement of the foot, and the horse was euthanatized. PMID- 2211331 TI - Type-I diabetes mellitus in a bull. AB - Although metabolic disorders are a frequent concern in cattle, they are not commonly recognized in bulls. The combination of hyperglycemia, acetonemia, ketonuria, and glycosuria in a bull was highly suggestive of diabetes mellitus. This uncommon diagnosis was confirmed by results of intravenous glucose tolerance testing. Results of the test and serum insulin values were further able to classify the disease in this bull as type-I diabetes mellitus. PMID- 2211332 TI - Congenital ichthyosis in a llama. AB - A 1-month-old male cria was examined because of diffuse hyperkeratosis and conjunctivitis that had existed since birth. The mucocutaneous junction of the nostrils as well as the neck, coronary bands, and axillary and inguinal regions were the most severely affected areas. Orthokeratosis involving the epidermis and follicular infundibula was observed on skin biopsy specimens. Electron microscopy revealed 4 to 6 granular layers and inter- and intracellular vacuolation in the stratum corneum; diagnosis of ichthyosis was established. PMID- 2211333 TI - What is your diagnosis? Hoof abscesses and cellulitis extending along the palmar aspect of the pastern of the left forelimb. PMID- 2211334 TI - The double death: the loss of the analyst in the analytic hour. PMID- 2211335 TI - The emergence of Fordham's model of development: a new integration in analytical psychology. AB - In bringing together some points from more than fifty years of Michael Fordham's work, I have endeavoured to show how there has emerged a consistent and original contribution to analytical psychology. In particular his ideas of the primary psychosomatic self and of whole objects preceding part objects are original to him. This contribution, with its implications for practice and theory, has in part reflected the capacity Fordham has for combining abstractions and the powerful evidence of clinical practice and observational material. This capacity has resulted in radical modifications of what I have called his emerging model of the mind (contrast Fordham, 13, with 19) and is in the best tradition of Jung's spirit and bequest to us in his body of published work. PMID- 2211336 TI - The hidden face of shame: the shadow, shame and separation. PMID- 2211337 TI - The presence of the third: intrusive factors in analysis. PMID- 2211338 TI - The resurrection of the dead: a Jungian approach to the mourning process. PMID- 2211340 TI - Age as a factor influencing the power and sensitivity of experiments for assessing body weight, testis size, and spermatogenesis in rats. AB - Data from 25 rats aged 60, 150, or 240 days (n = 75) were used to determine the number of observations per rat and or rats per treatment group needed to provide future experiments of known power and sensitivity. End points examined included body weight, testicular weight, number of resistant elongated spermatids, yields of germ cells from their younger progenitors, and germ cell:Sertoli cell ratios. Requirements differed in relation to the experimental power and sensitivity desired. However, the replication needed for detecting equivalent treatment effects on paired testes weight or the number of spermatids per gram of testis increased with age, and was twice as great for 240- vs 60-day-old rats. In contrast, approximately twice as many 60-day-old rats were required for detecting treatment effects on the number of spermatids per Sertoli cell than when 150- or 240-day-old rats were used. PMID- 2211339 TI - Preparation and characterization of monoclonal antibodies against sperm-specific lactate dehydrogenase C4. AB - LDH-C4, the testis-specific isozymes of lactate dehydrogenase (LDH), is the predominant LDH isozyme in mammalian spermatozoa. Nine monoclonal antibodies against mouse LDH-C4 have been developed. These antibodies were tested for cross reactivity with LDH-C4 from human testis and with LDH-1-5 from mouse and human testes by immunoelectrophoresis, bio-dot, and western blot assays. The results showed that all monoclonal antibodies were specific to LDH-C4 only: they did not react with LDH-1-5 from mice, nor from humans. The immunologic localization of the monoclonal antibodies on capacitated sperm was observed by indirect immunofluorescent assay. On mouse sperm the antibodies were bound to the tail only, but on human sperm eight antibodies were bound to the postacrosome, some to the neck and to the mid-piece. Most of the antibodies belonged to the Ig G class. PMID- 2211341 TI - Tumor necrosis factor and interleukin-1 stimulate testosterone secretion in adult male rat Leydig cells in vitro. AB - The actions of two cytokines, tumor necrosis factor (TNF) and interleukin-1 (IL 1), on testosterone production by dispersed adult testis cells and purified Leydig cells in culture were studied. In one set of experiments, testis cells from adult (90-day-old) rats were enzymatically dispersed. In another set of experiments, the dispersed testis cells were placed on a Percoll density gradient and were centrifuged to yield purified (greater than 85%) Leydig cells. Both whole testis cells and purified Leydig cells were cultured in the presence of varying doses of TNF or IL-1 with or without maximally stimulating doses of human chorionic gonadotropin (hCG). Both TNF and IL-1 stimulated basal secretion of testosterone in whole testis cells, as well as purified Leydig cells. Additionally, both TNF and IL-1 augmented maximally hCG stimulated testosterone secretion. Both cytokines stimulated testosterone secretion by dispersed testis cells as early as 4 hours, and the effect continued for up to 72 hours. The cytokines slightly, but significantly, stimulated testosterone production in purified Leydig cells after 24 hours, and continued for up to 72 hours. We have concluded from this data that TNF and IL-1 stimulate the testosterone secretion by adult rat Leydig cells. While this effect might be mediated through the action of the cytokines on testicular macrophages, there might also be a direct effect on the Leydig cell since augmentation of secretion occurred in purified Leydig cells, as well as whole testis cells. Therefore, TNF and IL-1 may serve as local regulators of Leydig cell function. PMID- 2211342 TI - Application of flow cytometry to studies on the human acrosome. AB - This study describes the use of flow cytometry combined with specific labelling of the human sperm acrosome using a FITC-labelled plant lectin (Arachis hypogea agglutinin). Localization of the label to the acrosome was encouraged by freezing the sperm for at least 24 hours at -70 degrees C prior to labelling. Studies of sperm from 53 normospermic men revealed that acrosome labelling followed a single normal distribution without the presence of subpopulations. The average fluorescence and degree of variation within the sperm population differed markedly between sperm samples. These differences could not be predicted by any of the normal criteria of sperm quality, including sperm morphology, vitality, and motility. Exposure of washed sperm to the calcium ionophore A 23187 in the presence of calcium at 37 degrees C, caused a time-related leftward shift in the distribution of acrosome fluorescence, indicating that this technique can be also used to monitor the acrosome reaction. PMID- 2211343 TI - Effects of hypophysectomy and alterations in spermatogenic function on Leydig cell volume, number, and proliferation in adult rats. AB - The two major objectives of this study were to determine (i) whether the pituitary is required to maintain Leydig cell number per testis, and (ii) whether alterations in spermatogenic function in the absence of LH can affect Leydig cell volume, number, and 3H-thymidine incorporation in vivo. Four experimental treatments tested the combinations of two factors: (i) the intact pituitary vs hypophysectomy (Hypox); and (ii) arrested vs active spermatogenesis. Subdermal Silastic capsules were used to deliver a low dosage of estradiol in addition to a low dosage of testosterone (TE), which arrested spermatogenesis, or a high dosage of testosterone (HTE) which maintained active spermatogenesis. All four treatments (TE, HTE, Hypox and Hypox-HTE) inhibited LH secretion for 16 weeks. Control rats were sham hypophysectomized. Leydig cell volume per testis and the volume of an average Leydig cell decreased 70-85% (P less than 0.01 vs controls) in all treated rats, whether deprived of LH (TE) or of all pituitary secretions (Hypox), and whether spermatogenesis was arrested (TE, Hypox) or maintained by exogenous testosterone (HTE, Hypox-HTE). This result suggested that LH was the only factor required to maintain Leydig cell volume, since the absence of other pituitary factors or alterations in spermatogenic function could not override or modify the effect of LH deprivation. No significant differences were found in Leydig cell number per testis or the proportion of Leydig cells labeled with 3H thymidine among control and experimentally treated rats. In contrast to Leydig cell volume, which depended on LH, Leydig cell number and Leydig cell division were maintained at control values in the absence of pituitary factors and spermatogenic function for 16 weeks. PMID- 2211344 TI - Long-term outcome following testicular ischemia in the rat. AB - Male germ cells are quite sensitive to interruption in blood flow. Eight weeks after subjection to 45 minutes of testicular ischemia, the spermatogenic epithelium of the rat remains significantly damaged, though other cell types are well preserved. The authors evaluated the testicular recovery of the rats at 8 and 72 weeks after the 45-minute period of warm ischemia. Twenty-eight rats were studied: 14 underwent 45 minutes of total left testicular ischemia; 14 received no treatment. Four rats from each group were necropsied at 8 weeks to document the ischemic injury. At 72 weeks, the 18 surviving rats were necropsied to evaluate the long-term outcome of the treatment. At 8 weeks, significant left testicular injury was documented. However, at 72 weeks there was no difference in testicular weight or sperm head count between the groups: in all 36 testicles, the repopulation index was 1.00, the epididymal index was 3+, the modified Johnsen index was 14, and the spermatic cord score was 7 (all are maximum obtainable scores). Neither contralateral orchiopathy nor injury to spermatic cord structures was observed. Our work shows that ischemia-induced testicular injury is fully reversible with time in this model. PMID- 2211345 TI - Absence of antisperm antibodies in anejaculatory men. AB - Antisperm antibodies were assessed in the serum samples of 73 men unable to ejaculate naturally and on the sperm cells of 13 of these men. None of the serum samples were found to be positive by sperm agglutination or sperm immobilization methods and antibodies were detected by an immunobead assay on the sperm cells of one of the 13 men examined. PMID- 2211346 TI - New antibiotic produced by Micromonospora globosa. PMID- 2211347 TI - New analogs of rosaramicin isolated from a Micromonospora strain. II. Structure determination. PMID- 2211348 TI - Antibiotics from basidiomycetes. XXXIII. Oudemansin X, a new antifungal E-beta methoxyacrylate from Oudemansiella radicata (Relhan ex Fr.) Sing. PMID- 2211349 TI - A new group of antibiotics, hydroxamic acid antimycotic antibiotics. III. Isolation and characterization of enactin congeners. PMID- 2211350 TI - Piperafizines A and B, potentiators of cytotoxicity of vincristine. PMID- 2211351 TI - Comparative studies on resistance to anthracycline derivatives between doxorubicin-resistant mouse lymphoblastoma L5178Y cells and mouse leukemia P388 cells. PMID- 2211352 TI - Effect of stereochemistry at the C-17 position on the antifungal activity of pradimicin A. PMID- 2211353 TI - Phthoxazolin, a specific inhibitor of cellulose biosynthesis, produced by a strain of Streptomyces sp. PMID- 2211354 TI - Duocarmycin SA, a new antitumor antibiotic from Streptomyces sp. PMID- 2211355 TI - Validamycin H, a new pseudo-tetrasaccharide antibiotic. PMID- 2211356 TI - Synthesis and biological activity of some 6 alpha-formamido penicillins modified in the 2 beta-methyl group. PMID- 2211357 TI - Synthesis and oral activity of ME1207, a new orally active cephalosporin. PMID- 2211358 TI - Isolation and partial characterisation of ACV synthetase from Cephalosporium acremonium and Streptomyces clavuligerus. PMID- 2211359 TI - Janthinocins A, B and C, novel peptide lactone antibiotics produced by Janthinobacterium lividum. I. Taxonomy, fermentation, isolation, physico-chemical and biological characterization. AB - Janthinocins A, B and C are novel antibacterial agents produced by Janthinobacterium lividum. They were isolated from fermentation broths and characterized by UV, IR, NMR and mass spectroscopy. They are cyclic decapeptide lactones with marked activity against aerobic and anaerobic Gram-positive bacteria and are 2 to 4 times more potent in vitro than vancomycin. Janthinocins A and B were also found to be effective in a Staphylococcus aureus systemic infection in mice. PMID- 2211360 TI - Janthinocins A, B and C, novel peptide lactone antibiotics produced by Janthinobacterium lividum. II. Structure elucidation. AB - The structures of janthinocins A, B and C, three novel macrocyclic peptide lactone antibiotics isolated from fermentations of Janthinobacterium lividum, were determined. The janthinocins are of particular interest because they contain three amino acid residues that have not previously been reported in natural products: Each contains erythro-beta-hydroxy-D-leucine while janthinocins A and B also contain beta-hydroxytryptophan and beta-ketotryptophan, respectively. PMID- 2211361 TI - YS-822A, a new polyene macrolide antibiotic. I. Production, isolation, characterization and biological properties. AB - A new polyene macrolide antibiotic, YS-822A was isolated from the culture filtrate of a mutant strain H-8 of Streptoverticillium eurocidicum var. asterocidicus S-822. Whereas the original S-822 strain produced not only YS-822 substances but also teleocidin as by-product which is well-known as a strong carcinogenic promoter, the mutagenized H-8 strain produced the antibiotic with only a trace amount of teleocidin. Chemical and biological characterizations of the antibiotic revealed that YS-822A (molecular formula: C37H59NO14) is a new polyene macrolide with a wide antifungal spectrum and a low acute toxicity. PMID- 2211362 TI - Himastatin, a new antitumor antibiotic from Streptomyces hygroscopicus. I. Taxonomy of producing organism, fermentation and biological activity. AB - Strain C39108-P210-51 (ATCC 53653), an actinomycete isolated from a soil sample collected in India, was found to produce a new antitumor antibiotic, designated himastatin. Taxonomic studies on its morphological, cultural and physiological characteristics identified this producing strain as Streptomyces hygroscopicus C39108-P210-51. Himastatin shows antimicrobial activity against Gram-positive bacteria but it is inactive against Gram-negative bacteria. Himastatin prolongs the life span of mice inoculated with P388 leukemia and B16 melanoma cells. PMID- 2211363 TI - Himastatin, a new antitumor antibiotic from Streptomyces hygroscopicus. II. Isolation and characterization. AB - The novel antitumor antibiotic himastatin was isolated from cultured broth of Streptomyces hygroscopicus (ATCC 53653) and purified by vacuum liquid chromatography, column chromatography, and crystallization. Degradation and spectroscopic studies have shown that himastatin contains valine, leucine, threonine, alpha-hydroxyisovaleric acid, 5-hydroxypiperazic acid and a dimeric hexahydropyrroloindole system. PMID- 2211364 TI - Chemical and biological properties of rubiginone, a complex of new antibiotics with vincristine-cytotoxicity potentiating activity. AB - A novel complex of isotetracenone (angucyclinone) group antibiotics was discovered from the cultured broth of Streptomyces griseorubiginosus No. Q144-2. The antibiotic consisted of six related factors, designated rubiginones A1, A2, B1, B2, C1 and C2. They significantly potentiated cytotoxicity of vincristine (VCR) against VCR-resistant P388 leukemia and Moser cells. PMID- 2211365 TI - Cloning of midecamycin(MLS)-resistance genes from Streptomyces mycarofaciens, Streptomyces lividans and Streptomyces coelicolor A3(2). AB - DNA containing genes for midecamycin(Mdm)-resistance was cloned from Streptomyces mycarofaciens ATCC 21454 (mdmA gene), Streptomyces lividans 66 (lrm gene) and Streptomyces coelicolor A3(2). The phenotype imparted to S. lividans and Streptomyces griseofuscus transformants by the cloned DNA segments indicates that they encode an MLS-type of resistance activity. The mdmA and lrm genes could be distinguished by the phenotype they conferred in S. lividans and S. griseofuscus, whereas the S. lividans lrm and S. coelicolor MLS genes appears to be identical on the basis of their restriction maps and behavior in S. lividans and S. griseofuscus. The DNA sequence of a 1.4-kb BamH I DNA fragment containing the mdmA gene indicates the presence of one complete orf whose deduced product exhibits a high similarity to the deduced product of the Streptomyces thermotolerans carB gene and several other bacterial MLS-resistance genes. PMID- 2211366 TI - Cloning and characterization of the sisomicin-resistance gene from Micromonospora inyoensis. AB - We cloned DNA fragments of sisomicin-producing Micromonospora inyoensis into Streptomyces plasmid vectors and identified Streptomyces lividans TK24 transformants expressing the M. inyoensis sisomicin-resistance (sisA) gene. The sisA gene was compared to the previously reported Micromonospora purpurea Kan-Gen (kanamycin-gentamicin)-resistance gene. While the restriction endonuclease digestion patterns of the two determinants appear to be divergent, the genes are nonetheless closely related, based on similar patterns and levels of aminoglycoside-resistance and their ability to cross-hybridize under stringent conditions. We have transformed recombinant plasmid pMD5-2, which carries the sisA gene, into our M. purpurea gentamicin-production strain and determined that gentamicin biosynthesis was not improved. PMID- 2211367 TI - Simaomicin (LL-D42067), a novel antibiotic from Actinomadura madurae. I. Taxonomy, fermentation and biological activity. AB - A new antibacterial antibiotic, designated simaomicin alpha (LL-D42067 alpha) was isolated from the fermentation broth of an actinomycete strain. Based on cultural, physiological, morphological and chemical characteristics, culture LL D42067 was identified as a new subspecies of Actinomadura madurae. Simaomicin alpha demonstrated potent activity against Gram-positive bacteria and was active in vivo against a variety of Eimeria species causing coccidiosis in chickens. PMID- 2211368 TI - Mechanism of action of atpenin B on Raji cells. AB - Atpenin B, a new antifungal antibiotic produced by Penicillium sp. FO-125, inhibited the growth of Raji cells (IC50, 30 microM). The incorporation of [14C]leucine and [3H]thymidine into Raji cells was inhibited by atpenin B with IC50 values of 0.10 and 0.12 microM, respectively. The incorporation of [14C]palmitate into the cells was not inhibited but its incorporation into lipid fractions was inhibited by atpenin B (IC50, 0.13-0.24 microM). Studies on the site of atpenin B action demonstrated that atpenin B decreases the cellular adenosine 5'-triphosphate (ATP) level in Raji cells with IC50 value of 0.020 microM, suggesting the inhibition of ATP-generating system by atpenin B. PMID- 2211369 TI - A novel series of milbemycin antibiotics from Streptomyces strain E225. II. Isolation, characterization, structure elucidation and solution conformations. AB - A novel series of milbemycin antibiotics were isolated from the fermentation broth of a Streptomyces species designated E225. The structures of the four main metabolites VM 44857 (1), VM 44864 (2), VM 44865 (3) and VM 44866 (4) were determined by NMR techniques. In addition we describe the solution conformations of the major metabolite VM 44857 (1). PMID- 2211370 TI - Intermolecular stacking of gilvocarcin V tetraacetate as evidenced by nuclear magnetic resonance studies. AB - The temperature-dependent and concentration-dependent 1H NMR studies as well as 13C-relaxation experiments on gilvocarcin V tetraacetate strongly suggest intermolecular stacking of the antibiotic solution. PMID- 2211371 TI - Sequence determination of actagardine, a novel lantibiotic, by homonuclear 2D NMR spectroscopy. AB - By combination of several 1H NMR techniques, the sequence of actagardine has been elucidated. It has been shown that it is a tetracyclic 19-residue peptide antibiotic. It differs from the previously described lanthionine-containing peptide antibiotics belonging to the lantibiotic class. PMID- 2211373 TI - Amphotericin B O-methyl oxime. Synthesis and biological properties. AB - Synthesis and biological properties of amphotericin B O-methyl oxime are described. The presence of an intact hemiketal ring in the antibiotic molecule appeared to be essential for its biological activity. PMID- 2211372 TI - Synthesis and biological activity of some amide derivatives of the lantibiotic actagardine. AB - A series of basic carboxamides of actagardine (1), a lantibiotic possessing good antistreptococcal activity, were synthetized. Some physico-chemical characteristics, in particular charge and lipophilicity, that influence water solubility were determined. The in vitro and in vivo activity was evaluated. The monocarboxamides were generally more active than actagardine against selected Gram-positive bacteria. The 3,3-dimethylamino-1-propylamide hydrochloride (4) showed good water solubility, bactericidal action and favourable antibacterial activity and it appears to be a suitable drug for further investigation. PMID- 2211374 TI - Structural specificity for biological activity of trichostatin A, a specific inhibitor of mammalian cell cycle with potent differentiation-inducing activity in Friend leukemia cells. AB - Biological activities of four chemically synthesized trichostatin-related compounds, (R)-trichostatin A, (S)-trichostatin A, (R)-trichostatic acid, and (S) trichostatic acid, were investigated. Assays of differentiation-inducing activity in Friend leukemia cells and G2-arresting activity in the cell cycle of normal rat fibroblast cells were used as monitoring systems for comparing the bioactivities of these compounds. The results clearly showed that both of the enantiomers of trichostatic acid had no activity in both the assay systems. In the case of (S)-trichostatin A, the antipode of naturally occurring trichostatin A, 50% effective concentrations were determined to be 50-70-fold higher than those of (R)-trichostatin A. The relationship between this ratio and the value of enantiomeric excess strongly suggests that (S)-trichostatin A is also biologically inactive. These results indicate that the absolute configuration and the presence of the hydroxamate group of trichostatin A are essential for its biological activity. PMID- 2211375 TI - Studies on orally active cephalosporin esters. VI. Synthesis and antimicrobial activity of 3-(3-isoxazolyl)oxymethylcephalosporin derivatives. AB - The synthesis and biological activities of a series of 3-(isoxazol-3-yl)oxymethyl cephalosporins are described. 7-[2-(2-Aminothiazol-4-yl)-(Z)-2 methoxyiminoacetamido]-3- [(isoxazol-3-yl)oxymethyl]-3-cephem-4-carboxylic acid (7a) showed potent activity against both Gram-positive and Gram-negative bacteria including some beta-lactamase producing species. Its pivaloyloxymethyl ester provided a good urinary recovery after oral administration to mice. PMID- 2211376 TI - Synthesis and antibacterial activity of C-2 alkenylthio-carbapenem derivatives. AB - A number of C-2 aminoalkenylthio-carbapenem derivatives possessing both the (5R,6R, 8S)- and the (5R,6S,8R)-stereochemistries have been prepared from the olivanic acids MM 22382 and MM 22383, respectively. Certain members of this new class of compounds displayed potent, broad spectrum antibacterial activity as well as improved stability to human kidney homogenate. PMID- 2211377 TI - Synthesis and biological activity of (cyclopentenopyridinium) thiomethylcephalosporins. AB - Substituted (cyclopentenopyridinium)thiomethyl groups were introduced as C-3 substituents of (6R,7R)-7-[(Z)-2-(2-aminothiazol-4-yl)-2-oxyimino]acetami docephalosporins. Structure-activity relationships of this class of cephalosporins are discussed on the basis of their MIC. The selected compounds, 3a and 4a (ME1221), having an acidic substituent, showed excellent in vivo efficacy and low toxicity. PMID- 2211378 TI - Synthesis and biological activity of 3-vinylthio- and 3-vinylthiomethylcephem derivatives. AB - The synthesis and biological properties of some 3-vinylthio- and 3 vinylthiomethylcephem derivatives are described. Both series possess potent antibacterial activity. Among them, 3-[(Z)-2-cyanovinylthiomethyl]cephem derivative was found to have an expanded antibacterial spectrum. PMID- 2211380 TI - Cochlioquinone A, a nematocidal agent which competes for specific [3H]ivermectin binding sites. AB - Cochlioquinone A, isolated from the fungus Helminthosporium sativum, was found to have nematocidal activity. Cochlioquinone A is a competitive inhibitor of specific [3H]ivermectin binding suggesting that cochlioquinone A and ivermectin interact with the same membrane receptor. PMID- 2211379 TI - Structure-activity relationships of elloramycin and tetracenomycin C. AB - The structure-activity relationships of the anthracycline-related antibiotics of the tetracenomycin C/elloramycin-type were investigated by derivatization of elloramycin (1) and elloramycinone (2). During hydrolysis experiments a unique transglycosylation reaction was discovered, converting elloramycin (1) into isoelloramycin (10) by treatment with anhydrous trifluoroacetic acid. Following the proposed structure-activity relationship concept, 8-O-methylelloramycinone (14) was synthesized from elloramycinone (2), and was shown to be the most active derivative according to the proliferation inhibition assay against murine L1210 leukemia cells. PMID- 2211381 TI - FR900403, a new antifungal antibiotic produced by a Kernia sp. PMID- 2211383 TI - Neopyrrolomycin, a new chlorinated phenylpyrrole antibiotic. PMID- 2211382 TI - Bioconversion of monensin by a soil bacterium, Sebekia benihana. PMID- 2211385 TI - Synthesis and structure-activity relationships of monocarbams leading to U-78608. PMID- 2211384 TI - Depsidomycin, a new immunomodulating antibiotic. PMID- 2211387 TI - Feeding value of wood sugar concentrate for feedlot cattle. AB - Six crossbred steers (344 kg) with "T" cannulas in the rumen and proximal duodenum (6 cm from the pyloric sphincter) were used in a crossover experiment to evaluate the feeding value of wood sugar concentrate (WSC) in a finishing diet for feedlot steers. Composition of WSC was as follows: DM, 49.5%; ash, 19.2%; N, .1%; hydrolyzable sugars, 38.9% and lignosulfonate, 28.8%. Dietary treatments consisted of a finishing diet based on steam-flaked corn supplemented or not supplemented with 10.5% WSC (DM basis). Adding WSC to the diet increased (P less than .10) passage of OM to the small intestine. However, passage of N constituents (non-ammonia N, microbial N and feed N) was not affected (P greater than .10). Postruminal digestion of OM and N was depressed (P less than .05) 11.5% and 6.7%, respectively, with WSC supplementation. Total tract digestibilities of OM and GE were depressed (P less than .01) 4.1 and 4.2%, respectively. Adjusting for constituent passage of the basal diet, estimated digestible OM and DE values for WSC used in this trial were 42.7% and 2.02 Mcal/kg. WSC (DM basis) had 76% and 64%, respectively, of the energy value of hemicellulose extract (masonex) and cane sugar molasses. Because a high level (10% of diet DM) of WSC depressed postruminal N digestion, WSC levels of feedlot diets that are marginal in protein should not exceed 5% of diet DM. PMID- 2211386 TI - Effect of roasted or raw peanut kernels on lactation performance and milk composition of swine. AB - A lactation trial involving 105 sows was conducted to determine the effect of 12% roasted or raw, ground, whole, shelled peanuts on sow weight change during lactation, feed intake, piglet and litter weight gain, milk composition, and days to return to postweaning estrus. The trial was conducted using three sow groups during two farrowing seasons, summer (July to September) and winter (December to February). Diets were based on corn plus soybean meal. Diets contained either 5% animal fat or equivalent added fat from 12% roasted or raw, ground, shelled peanuts. The replacement of animal fat by roasted or raw peanuts had no effect (P greater than .20) on sow weight change, average daily feed intake during lactation or days to estrus postweaning, or on piglet weight gain or survival. Milk composition (percentage fat and protein) was not altered (P greater than .20) by source of fat in the summer; however, in the winter, sows fed roasted peanuts had higher (P less than .05) milk fat and protein percentage at 3 d postfarrowing than other treatment groups. At d 7, sows fed 12% roasted or raw peanuts had higher (P less than .05) milk protein than sows fed 5% animal fat. Sows farrowing in the summer had greater (P less than .01) weight loss and consumed less (P less than .05) feed during lactation than sows farrowing in the winter. Sows farrowed in the summer had larger (P less than .05) litters at birth and 14 d postfarrowing and greater (P less than .10) piglet and litter weight gain postfarrowing than those farrowed in the winter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2211388 TI - Relationship of ultrasound speckle to marbling score in cattle. AB - A subjective, but repeatable, scoring system was devised to quantitate ultrasound speckle in tomograms of the longissimus muscle over the 12th rib. Speckle scores in 11 of 14 groups of cattle (n = 619) were highly correlated (P less than .001) with carcass marbling score. Live animal speckle scores classified carcasses as Select or Choice with 77% accuracy. Similar accuracy was achieved as much as 148 d before slaughter by adjusting for the regression of speckle scores with days on feed. Marbling scores were not distributed normally with both positive skewness and kurtosis (P less than .001). The procedure exploited an unmodified low-cost ultrasound system; scores were estimated instantly from the monitor image. This ability to predict carcass grade at distant dates might be incorporated into a strategy to cluster feedlot cattle into outcome groups for more effective marketing. The results suggest that mathematical analysis of the ultrasound radio frequency signal or pixel map statistics might reveal parameters that could improve accuracy and precision of the method and, conceivably, could predict specific attributes of beef palatability. PMID- 2211389 TI - The effect of a monensin ruminal delivery device on performance of cattle grazing pasture. AB - A total of 28 trials utilizing 2,262 steers and heifers were conducted to evaluate a sustained monensin2 ruminal delivery device (RDD) on the daily gain of grazing cattle. Five series of trials, with four to eight trials per series within a grazing season, were conducted to evaluate the daily gain response under different environmental conditions and locations. Pastures grazed included both summer (cool- and warm-season grasses and native range) and winter (rye, ryegrass and wheat) growing pastures. The experimental design for all trials in each of five series was a randomized complete block with initial weight or breed as the blocking factor. The treatments compared in series I, III, IV and V (20 trials) were a control and a single RDD, whereas in series II (eight trials), a 2 x 2 factorial was utilized that compared RDD and estradiol 17-beta controlled release implants. In the five series of trials, the monensin RDD increased daily gain .04 (P = .002), .03 (P = .07), .09 (P = .01), .05 (P = .10) and .08 kg (P = .04) compared with the controls. Use of the RDD provided an effective method of achieving consistent monensin delivery and weight gain improvement without requiring the extra labor needed to administer monensin via hand-feeding or self feeding supplements, blocks or loose mineral. PMID- 2211391 TI - Factors to adjust litter weight of pigs to a standard 21 days of age. AB - Factors to standardize litter weights of nursing pigs to 21 d of age were calculated from daily weights measured on 64 crossbred litters from 10 to 32 d of age. The results were compared to published factors derived from a data set of Duroc pigs weighed every 3 to 4 d. Dams in the present study were white crossbred sows and gilts, and sires were maternal or terminal breed types. Multiplicative factors were calculated by dividing the mean 21-d litter weight (LW21) by mean daily litter weight. Linear and quadratic regression coefficients of LW21 on age at weighing were fitted to the factors (R2 = .997). The final equation for adjusting litter weights to a 21-d basis was 2.5246 - .1041 x (d of age) + .0015 x (d of age)2. There were good agreement with published factors for d 19 to 25, but divergence for younger and older litters resulted in significant differences between the linear coefficients. These differences may be due to departure from a linear growth curve, which daily measurements would incorporate, or differences in sow populations. Thus, use of the new factors should be considered for white crossbred sow populations. A least squares analysis indicated that LW21 was significantly altered by parity, not by the number of pigs allowed to nurse or by breed of sire. After adjustment to 21 d, litter weights also should be adjusted for differences in parity before evaluating sow productivity, by using additive factors such as those recommended by the National Swine Improvement Federation. PMID- 2211390 TI - Influence of nutritional restriction during late gestation on production measures and passive immunity in beef cattle. AB - A 2-yr study was conducted to examine the effects of nutritional restriction of beef cows during the last 90 d of gestation on neonatal immunity and production. Cows were fed corn silage, soybean meal diets; dietary treatments consisted of 1) control (CO), 100% of the NRC (1984) requirements for protein and energy, or 2) restricted (RS), 57% of the NRC requirements for energy and protein. All cows received adequate amounts of this diet postpartum. Each year, 26 Angus cows were grouped by age and weight:height ratio (WT:HT) and allotted randomly to treatments. Calves born to dams within each nutritional treatment group were allotted to one of two colostral treatments: 1) colostrum from their dam, or 2) colostrum from a cow from the other nutritional treatment group. Calves from restricted dams had higher cortisol (33.8 vs 26.1 ng/ml) and lower triiodothyronine (T3) (3.82 vs 4.01 ng/ml) concentrations (P less than .05). Maternal nutrition did not affect either colostrum immunoglobulin G (IgG) concentration (43.0 vs 39.5 mg/ml for RS and CO, respectively) or the calves' serum IgG concentration (19.06 vs 20.17 mg/ml IgG at 24 h for RS and CO, respectively). Yet, calves fed colostrum from restricted cows tended to have lower serum IgG concentration (17.2 vs 22.0 mg/ml IgG at 24 h). PMID- 2211392 TI - Evaluation of condensed molasses fermentation solubles as a nonprotein nitrogen source for ruminants. AB - Condensed molasses fermentation solubles (CMS), an effluent from the production of lysine, was evaluated as a nonprotein nitrogen supplement for ruminants by measuring the availability of its nitrogen to rumen microorganisms grown in batch cultures and by comparing CMS to urea as a source of supplemental nitrogen for growing cattle. In vitro dry matter digestion studies showed that, with 1 ml or less of rumen inoculum, microbial digestion was enhanced more (P less than .05) by the addition of CMS than by the addition of urea to 100 mg of cellulose. These stimulatory effects of CMS were absent when either the amount of inoculum (5.0 ml) or cellulose (250 mg) was increased and when wheat straw or alfalfa replaced cellulose as the substrate. Growth rate and feed intake for cattle fed a high cob/cracked-corn diet containing 2.5 or 5.0% CMS were lower (P less than .05) than for cattle fed the control diet containing urea. Digestibility of dry matter, crude protein, neutral detergent fiber and acid detergent fiber were reduced (P less than .05) by the addition of CMS. Addition of CMS also decreased feed utilization, although the differences were not statistically significant. In conclusion, the nitrogen in CMS was available to rumen microorganisms growth in batch culture; however, CMS was not satisfactory as a substitute for all the urea in a diet for growing cattle containing over 45% of dietary N from the supplemental N source. PMID- 2211393 TI - Management practices and their association with reproductive health and performance in Colorado beef herds. AB - An observational study was conducted to quantify the effects of management practices on reproductive performance and disorders of beef cows. The study population consisted of 44 randomly selected Colorado cow-calf herds monitored for disease and reproductive events as part of the National Animal Health Monitoring System. The managers of the herds were surveyed with a standardized questionnaire to determine specific management characteristics of their operations. Data were analyzed using the random-effects multiple logistic regression model. Outcomes of interest were calving rate, herd incidence rates of dystocia and combined reproductive disorders, and calf mortality rate. A higher calving rate was associated (P less than .01) with a decreased percentage of replacement females in the herd, a shorter breeding season, a smaller herd size, and a lower percentage of bulls being used as yearlings. Incidence rates of both dystocia and combined reproductive disorders were found to be lower (P less than .01) in herds that were fed cottonseed cake as a winter supplement, but higher (P less than .01) in herds that were fed grass hay as a winter supplement. Herds located in the mountains of Colorado had lower (P less than .01) incidence rates of dystocia and reproductive disorders than herds located in the eastern plains. Calf mortality rate was found to be higher (P less than .05) with calving seasons that began earlier in the year. Higher calf mortality rates were associated (P less than .05) with an increased incidence of dystocia, the commingling of cattle on summer range, and smaller herd size. PMID- 2211394 TI - Some alternatives to calving date and interval as measures of fertility in beef cattle. AB - Records of 594 calving dates and 493 calving intervals collected from a herd of Retinta beef cows in southwest Spain were studied. Their efficacy as reproductive measures were compared when a long breeding season was utilized. Variables used were date of present calving (DOC), date of subsequent calving (DOSC), time from start of breeding season to calving (TBSC), interval to next calving (CI), two adjustments of calving interval by subtracting the time that bulls were not available to the cow from actual CI (ACI1 and ACI2), and three scores. Period score (SCOR) measured the 20-d increment of the 220-d calving season in which the cow calved. Pair score (PAIR) was computed by subtracting the deviation of calving interval from 365 d from the average SCOR of the two calvings involved. Adjusted pair score (APAIR) was calculated in the same way as PAIR, but using ACI1 instead of CI. Heritability estimates for DOC, SCOR, and DOSC and CI were .16, .14, .13 and 0, respectively. Heritabilities of all other measures ranged from .01 to .06. Repeatability estimates for DOC, SCOR, DOSC and CI were .29, .28, .34 and .14, respectively. Repeatability values were .28, .18, .18, .23 and .32 for TBSC, ACI1, ACI2, PAIR and APAIR, respectively. Genetic and phenotypic correlations among CI and its alternative measures were very high and favorable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2211395 TI - Measuring physiological responses of animals to environmental stressors using a microcomputer-based portable datalogger. AB - The microcomputer-based datalogger system described in this report provides excellent flexibility for accurate recording of signals from a variety of sensors at programmable intervals. The small size of the unit permits applications in many research situations in which physiological and microclimate records are required from unrestrained animals. Data presented from two experiments with cattle with ad libitum access to feed demonstrate the utility of the system. The high resolution and frequent measurements illustrate the fine detail of thermoregulatory responses of cattle (as represented by tympanic temperature) to sequential moderate and hot environments, the association of feeding activities with tympanic temperature at moderate conditions, and the disruptions in thermoregulatory function and feeding activities in hot conditions. A comparison of four anatomical sites (two internal, two sub-dermal) for measuring body temperature also illustrates shortcomings in using sub-dermal measures to reflect responses to dynamic ambient environments. PMID- 2211396 TI - Animal performance, plasma hormones and metabolites in Holstein and Belgian Blue growing-fattening bulls. AB - Six Holstein (light-muscled type) and six Belgian Blue bulls (double-muscled type) were fed a finishing diet. Average daily gain was 1.36 kg for the Holstein bulls vs 1.24 kg for the Belgian Blue bulls (P less than .05). Holstein bulls consumed more feed (2.3 vs 1.8 kg/100 kg body weight, P less than .001) than the Belgian Blue bulls. The dressing percentage (55.4 vs 65.8%, P less than .001) and the proportion of muscle (56.1 vs 71.3%, P less than .001) in the carcass were less, whereas the proportions of adipose tissue (28.3 vs 15.4%, P less than .001) and bone (15.7 vs 13.4%, P less than .05) were higher in the Holstein bulls. Plasma creatinine determined in samples obtained once a week was lower (11.0 vs 20.3 mg/liter, P less than .001) in the Holstein bulls. In contrast, Holstein bulls tended to produce more triiodothyronine (2.3 vs 1.8 nM, P less than .10), tetraiodothyronine (71.9 vs 54.7 nM, P less than .10) and insulin-like growth factor I (IGF-I; 340 vs 205 ng/ml, P less than .20) than the Belgian Blue bulls. Growth hormone, insulin, IGF-I and testosterone were measured at 20-min intervals during two 24-h periods. In wk 6, Holstein bulls tended to produce more growth hormone than the Belgian Blues, as indicated by higher total peak area (3,185 vs 2,431 ng), peak amplitude (34.1 vs 22.6 ng/ml, P less than .10) and baseline (4.6 vs 3.3 ng/ml, P less than .20). In wk 27, the trends were opposite.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2211397 TI - Effects of gender and genotype on the response of growing pigs to exogenous administration of porcine growth hormone. AB - Sixty crossbred pigs (Large White x Landrace) were used in a 2 x 2 x 2 factorial experiment to investigate the effects of gender (intact males vs females) and strain (A vs B) on the response to exogenous porcine growth hormone (pGH) administration (0 [excipient-treated] vs .1 mg pGH.kg live weight-1.d-1). All pigs had ad libitum access to their diet; pGH was administered daily from 60 to 90 kg live weight. All aspects of growth performance and body composition were affected to different degrees by gender and pGH. Strain A pigs had a higher capacity for protein accretion, superior growth performance and contained less fat in the eviscerated carcass and empty body compared with Strain B pigs. Within each strain, intact males ate more feed, had a higher rate of protein deposition and exhibited faster and leaner growth than females. Exogenous pGH administration increased average protein deposition and growth rate by 84 and 34%, respectively, and reduced average feed intake, fat deposition rate, feed:gain and carcass fat content by 14, 59, 37 and 33%, respectively. The magnitude of the changes in growth performance, tissue accretion rates and body composition elicited by pGH were independent of strain. However, within each strain the improvement in feed:gain and reduction in carcass fat measurements elicited by pGH were proportionately larger for females than for intact males. PMID- 2211398 TI - Growth and hormonal response of intact and castrate male cattle to trenbolone acetate and estradiol. AB - Effects of castration and anabolic implants on weight gain, rib soft tissue composition and serum hormones were studied in cattle using a completely random design with a 2 x 2 factorial arrangement. Half of 16 bulls and 16 steers (Angus or Angus x Brahman) aged 9 mo and weighing 290 kg were treated with an implant (200 mg trenbolone acetate and 24 mg estradiol). Half of each group were not treated with an implant. A growing diet was fed for 95 d and half the animals in each group were slaughtered. Animals in the treated groups were reimplanted with trenbolone acetate and fed a finishing diet for 84 d and slaughtered. Percentage dry matter, fat and protein were determined on soft tissue from the 9-10-11th rib. Two blood samples were collected from each animal every 2 wk. Serum was assayed for five hormones. During the growing phase, untreated and treated bulls and treated steers gained more weight and had leaner rib sections that untreated steers (P less than .05); after the finishing phase, there were no differences among groups. Untreated steers had lower insulin-like growth factor (IGF-I) and higher cortisol concentrations during both phases of growth than untreated bulls did (P less than .05). Treatment with implants increased IGF-I concentrations in steers during both phases and reduced cortisol during the finishing phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2211399 TI - Dose-response relationships between porcine somatotropin, muscle composition, muscle fiber characteristics and pork quality. AB - The dose-dependent effects of porcine somatotropin (pST) on cellular aspects of skeletal muscle growth, muscle composition and measures of pork quality were investigated in growing barrows and gilts. Eighty crossbred pigs weighing 46 kg were assigned randomly to receive daily subcutaneous injections of 0, 30, 60, 120 or 200 micrograms pST/kg BW until they weighed 100 kg. Semitendinosus muscle weights were increased with pST dose (linear, P less than .001) by 21%. Percentage of type I and type II muscle fibers was not changed with pST, but cross-sectional area of type I and type II fibers was increased in parallel with muscle weight. Percentage of moisture increased (P less than .01) and percentage of lipid decreased (P less than .01) as pST dose increased. The pH of the longissimus 24 h postmortem increased (P less than .01) .1 to .2 units with increasing pST dose, but subjective evaluation for color, firmness and wateriness of the longissimus indicated no discernible treatment effect. Gardner color difference meter "Rd" and "A" values decreased (P less than .01) with a pST dose of 60 micrograms/kg or more, signifying a slightly darker and less red color, respectively, of the longissimus muscle. Weight loss of loin chops 2.54 cm thick cooked to 71 degrees C (20.3% to 23.7%) and shear force of cores 1.27 cm in diameter (2.89 to 3.76 kg) were not related to pST treatment or dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2211400 TI - Myofibrillar protein turnover in feed-restricted and realimented beef cattle. AB - The objective of this study was to determine the effect of feed restriction and repletion on myofibrillar protein turnover in cattle. Crossbred steer calves (n = 12) about 310 d of age were assigned randomly to a diet of corn and silage that was 1) provided ad libitum for 146 d (ALC) or 2) restricted so steers gained .2 kg/d for 80 d but received ad libitum access to feed thereafter for 66 d (RFC). At 27, 55, 97, 118 and 146 d a 24-h urine sample and a blood sample were obtained. Urine was analyzed for N tau-methylhistidine (N tau-MH), creatinine (C), urea nitrogen (UN) and total nitrogen (TN). Serum samples were analyzed for hydroxyproline (HYP), C and albumin (A). Body weights were lower (P less than .05) in RFC at 55, 97, 118 and 146 d. Excretion of N tau-MH was lower (P less than .05) in the RFC at 27 and 55 d but higher at 118 d. Urinary C excretion was higher in ALC at the last four sample times. Urinary UN and TN excretion were lower (P less than .05) in RFC at 55, 97 and 118 d; urinary UN also was lower (P less than .05) at d 146. Serum A was higher (P less than .05) in ALC at 55 and 118 d, respectively. Serum HYP was higher (P less than .05) in RFC at 27 and 55 d. Calculated myofibrillar protein breakdown rates (FBR) and fractional synthesis rates (FSR) were higher (P less than .05) in RFC at the last two sampling periods; FSR was lower for the RFC at the first sampling period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2211401 TI - Evaluation of attributes that affect longissimus muscle tenderness in Bos taurus and Bos indicus cattle. AB - Biological tenderness differences between longissimus muscles (LM) from Bos indicus and Bos taurus breeds were evaluated. Steers and heifers of Hereford x Angus (H x A, n = 10), 3/8 Sahiwal x H, A or H x A (3/8 SAH, n = 6) and 5/8 Sahiwal x H, A or H x A (5/8 SAH, n = 11) crosses were utilized. Muscle temperature and pH were monitored every 3 h for the first 12 h and at 24 h. Samples were obtained within 1 h and at 24 h postmortem from the LM for determination of calcium-dependent protease (CDP) -I and -II and CDP inhibitor (INH) activities. At 1 and 14 d postmortem, LM samples were removed for determining cathepsin B and B + L activity, soluble and total collagen, sarcomere length, muscle-fiber histochemistry, shear force and sensory-panel traits. Data were analyzed using least squares procedures with fixed effects of breed cross, sex and their interaction. No significant breed cross effects were observed for carcass traits or rates of pH and temperature decline. Steaks from H x A had lower (P less than .05) shear-force values and higher (P less than .05) sensory scores for tenderness at 1 and 14 d postmortem than steaks from 3/8 and 5/8 SAH. Correspondingly, 5/8 SAH had lower (P less than .05) myofibril fragmentation indices than H x A at 1, 3, 7 and 14 d postmortem. Breed cross effects were not significant for sarcomere length, fiber types, soluble and total collagen, cathepsin B and B + L specific activity, CDP-I and -II activity and INH activity within 1 h postmortem. However, INH total activity/100 g of muscle was greater (P less than .01) at 24 h postmortem for 5/8 SAH (208.8 +/- 14.8) and 3/8 SAH (195.6 +/- 19.3) than for H x A (136.3 +/- 14.9). For H x A, SDS-PAGE revealed that by d 1 desmin had been subjected to proteolysis, and by d 14 desmin could not be detected, but a 30,000-dalton component was clearly evident. However, in 5/8 SAH, desmin remained visible at d 14 without a 30,000-dalton component appearing. This reduced protein hydrolysis may account for less tender meat in SAH; INH apparently influences this process. PMID- 2211402 TI - Effect of select menhaden fish meal in starter diets for pigs. AB - Two trials were conducted to evaluate a select menhaden fish meal (SMFM) as a protein source in starter diets for 390, 3-wk-old weaned pigs. Initial weights averaged 4.8 and 5.5 kg in Trials 1 and 2, and trials were conducted for 5 and 4 wk, respectively. Diets in Trial 1 were formulated by substituting levels of 0, 4, 8, 12, 16 or 20% SMFM for soybean meal plus corn on a protein basis. The 20% fish meal diet contained no soybean meal; all diets contained between 19.8 and 20.2% CP, between 1.34 and 1.40% lysine and 25% dried whey. Replacement of soy protein with fish meal elicited a quadratic improvement (P = .01) in cumulative ADG and average daily feed intake (ADFI) by the end of wk 5. The diet containing 8% SMFM resulted in the maximum observed ADG; however, the maximum ADFI occurred in pigs fed the diet containing 12% SMFM. Breakpoint analysis indicated that 4.5 and 9.3% SMFM maximized ADG and ADFI, respectively. Addition of SMFM did not affect efficiency of feed utilization (F/G). In Trial 2, a 2 X 3 factorial with two levels of dried whey (10 or 20%) and three levels of SMFM (0, 4 or 8%), a SMFM X dried whey interaction (P less than .05) was observed for cumulative ADG and F/G by the of wk 4 with greater benefit from SMFM with 10% than with 20% dried whey.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2211403 TI - Interrelationships of dietary sodium, potassium and chloride on growth in young swine. AB - In a preliminary experiment, pigs fed a purified diet gained at the same rate as pigs fed a natural ingredient diet if the purified diet was formulated to provide 150% of the Na, K and Cl requirements. Subsequent experiments were designed to determine the interrelationships of dietary Na, K and Cl. Pigs were fed diets with Na (.03% to .60%), K (.1% to 1.0%) and Cl (.03% to .60%) levels arranged in a three-factor central composite design. Over the range of Na levels, predicted gain increased by .07 kg/d. Within this dietary range no interactions between Na and K or Na and Cl were observed, but changes in growth due to dietary K level were dependent on the dietary Cl level. Using canonical analysis of the response surface, a minimax of the observed K and Cl interaction was calculated to be .57% K and .27% Cl. An imbalance of dietary K and Cl was predicted to depress gain, and an increase in gain was predicted by a 1:1 addition of K and Cl above or below the minimax. The results of a third experiment failed to confirm that additions of K and Cl in a 1:1 ratio above the minimax altered gain (P greater than .10). Experiment 4 confirmed that an imbalance of K and Cl altered growth of pigs. At .1% K, an increase in dietary Cl from .03% to .57% depressed gain by .07 kg/d; at 1.1% K the same increase in dietary Cl improved gain by .16 kg/d (P less than .07). These results suggest that dietary K and Cl levels have an interactive effect on pig growth. PMID- 2211404 TI - Evaluation of various extracted vegetable oils, roasted soybeans, medium-chain triglyceride and an animal-vegetable fat blend for postweaning swine. AB - A total of 280 crossbred pigs weaned at 21 d of age and weighing approximately 6 kg were utilized in five replicates to evaluate pig growth responses when fed a basal diet or one of several dietary lipid sources during a 4-wk postweaning period. A basal corn-soybean meal-corn starch-dried whey diet was compared with diets supplemented at a 7.75% level with one of the following lipid sources: corn oil, coconut oil, soybean oil, medium-chain triglyceride (MCT) or an animal vegetable blend. A sixth treatment evaluated a roasted soybean diet formulated to an energy:lysine level equivalent to that of the fat-supplemented diets. In Exp. II, 36 crossbred weanling barrows were used to determine apparent fat and N digestibilities when soybean oil, roasted soybean, coconut oil or the MCT supplemented diets were fed. Although pigs fed coconut oil grew somewhat faster, fat inclusion generally did not increase pig growth rate or result in lowered feed intake during the initial weeks postweaning; during the latter portion of the starter phase the addition of dietary fat resulted in a higher growth rate but feed intake was unaffected, resulting in an overall improvement in feed-to gain ratio (P less than .05) for all but the roasted soybean diet. Pigs fed coconut oil had higher serum triglyceride and lower serum urea concentrations than did pigs fed diets containing most other lipid sources. Pigs fed MCT and coconut oil diets had a higher (P less than .01) apparent fat digestibility during the initial 2 wk postweaning than pigs fed soybean oil or roasted soybean diets. Pigs fed MCT and roasted soybeans had poorest growth rates; apparent fat and N digestibilities were lowest (P less than .05) for the roasted soybean diet. PMID- 2211405 TI - Effects of intramuscular administration of recombinant bovine interferon-alpha I1 during the period of maternal recognition of pregnancy. AB - One hundred ewes were utilized to determine the effects of interferon supplementation on the number of ewes pregnant and embryonic survival. Ewes were checked twice daily (0700 and 1600) for estrus using fertile rams. On d 12 through 16, ewes received twice-daily i.m. injections of either recombinant bovine interferon alpha I1 (2 mg IFN) or vehicle. Ewes remained penned with rams and were observed for subsequent estrous activity for at least 35 d after mating. To determine the number of fetuses and corpora lutea, all ewes were subjected to one surgery during mid-pregnancy (d 45 to 80). More (P less than .05) ewes were pregnant after treatment with IFN vs vehicle (45 of 49, 92% vs 37 of 49, 76%, respectively). The interestrous interval for ewes that were treated with IFN and did not conceive was longer (P less than .05) than for ewes given vehicle (26 +/- 1 vs 17 +/- 2 d, respectively). Embryonic survival (98.2 vs 87.9%; P less than .05), calculated as the number of fetuses present at the time of laparotomy and expressed as a percentage of the ovulation rate, and percentage of ewes with 100% fetal survival (96 vs 76%; P less than .05) were greater after treatment with IFN. It was concluded that supplementation of IFN increased both the number of ewes pregnant and embryonic survival. PMID- 2211406 TI - Biological and immunological luteinizing hormone activity and blood metabolites in postpartum Brahman cows. AB - Multiparous Brahman cows were assigned by order of calving and sex of calf to groups to be fed to maintain body condition score (BCS) of 6 or greater (M; n = 10) or to lose BCS (L; n = 10). Blood samples were collected weekly for progesterone analysis and at 15, 30 and 45 d after parturition at 15-min intervals for 6 h for determination of immunological (ILH) and biological (BLH) luteinizing hormone. Serum concentrations of ILH were determined using a double antibody RIA procedure, whereas BLH was determined using a rat interstitial cell testosterone bioassay (RICT). By 45 d after parturition 7 of 10 M cows had returned to estrus. Therefore, comparisons between groups were made on d 15 and 30 postpartum. Cows in the M group had a shorter (P less than .001) interval to first estrus (46.7 d) than did L cows (91.2 d). The concentrations of bioactive and immunoactive LH were parallel between d 15 and 30 postcalving. However, a day x treatment interaction (P less than .05) showed that episodic BLH concentrations (ng/ml) decreased with day postpartum in L, but increased in M cows from d 15 to 30 postcalving. Likewise, relative biological activity, as measured by B:I ratios, decreased between d 15 and 30 in L cows, whereas it increased in M cows during the same period (B:I x day interaction; P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2211407 TI - Synthesis of heat stress proteins in lymphocytes from livestock. AB - Cultured bovine, equine, ovine and chicken lymphocytes responded to heat stress by the increased synthesis of a specific set of proteins known as heat stress proteins (HSP). Proteins with molecular weights of 70 and 90 kDa were synthesized in all species. Additional proteins were found in bovine, ovine and chicken lymphocytes. A time course of induction showed an increased synthesis of some of these proteins with only 30 min of heat stress and of several proteins with 60 min of heat stress. A specific monoclonal antibody was used to identify HSP70 as one of the stress proteins in bovine lymphocytes. Cells from these animals are capable of responding to heat stress by the production of heat stress proteins. These may be of physiological importance. PMID- 2211408 TI - Libido, hormone concentrations in blood plasma and semen characteristics in Holstein bulls. AB - Relationships among bull libido, serum hormone concentrations and semen characteristics were studied using 18 Holstein bulls that were 4 to 5 yr old. The hormones studied included testosterone, estradiol (E2), prolactin (PRL), LH and cortisol. Two ejaculates were collected three times per week from each bull during a 5-wk trial. During the last week of the trial, on a day semen was not collected, blood was collected from indwelling catheters every 15 min for 6 h to determine the hormonal profiles of each bull. On the following day, blood was sampled every 10 min before and after the time of semen collection. Libido factors were quantified, and semen volumes and sperm concentrations were recorded. The libido factors included reaction time to first service, latency time between the first and second semen collections, and duration of time the bull mounted the teaser prior to the first (TM1) and second (TM2) semen collection. Average reaction and latency times were correlated (r = .524; P = .026), as were TM1 and TM2 (r = .597; P = .015). Latency times were correlated with average TM2 (r = .669; P = .003). Average PRL concentrations were correlated with average latency times (r = .467; P = .05). Low libido bulls tended to have higher E2:testosterone ratios than did high libido bulls. Both PRL and cortisol concentrations increased at semen collection. PMID- 2211409 TI - Reproductive function and feedlot performance of beef heifers actively immunized against GnRH1. AB - Two trials were conducted to examine reproductive function and feedlot performance by heifers after active immunization against GnRH. In trial 1, heifers were not immunized or were immunized with one of three doses of a GnRH KLH (keyhole limpet hemocyanin) conjugate in Freund's complete adjuvant. Antibodies against GnRH were not detectable in non-immunized heifers (n = 9). However, antibodies against GnRH were noted in all immunized animals (n = 30) within 8 wk of primary immunization; anti-GnRH antibody concentrations were at a maximum 16 to 20 wk after immunization. This increased anti-GnRH titer was associated with a decreased serum concentration of progesterone. Ovarian and uterine weight and tissue concentrations of LH and GnRH receptor were reduced (P less than .05) by immunoneutralization of GnRH. Similarly, immunization against GnRH reduced (P less than .05) weight gain during feedlot confinement. In trial 2, feedlot performance after insertion of anabolic steroid implants (Synovex H) was evaluated in non-immunized heifers (n = 15), heifers actively immunized against GnRH-KLH (n = 15) or KLH alone (n = 15), or non-immunized heifers treated with melengestrol acetate (MGA; n = 15). Serum concentrations of progesterone were depressed in anti-GnRH and MGA-fed groups, but ovarian and uterine weights were depressed (P less than .05) only in heifers immunized against GnRH. Total weight gain and gain during the final 4 wk of confinement did not differ (P greater than .05) among groups with steroid implants. The GnRH-KLH conjugate is an effective immunogen in heifers, leading to suppression of reproductive activity. The depression of weight gain that attends development of anti-GnRH titers may be reversed by use of implants that contain anabolic steroids. PMID- 2211410 TI - Observations on the cooling and cryopreservation of pig oocytes at the germinal vesicle stage. AB - This study examined the viability of pig oocytes at the germinal vesicle stage following cooling or cryopreservation. Cumulus-intact oocytes (n = 641) were collected from slaughterhouse pig ovaries and used in two experiments. In Exp. I the viability of 1) control, 2) cryoprotectant control (CC, 1.5 M glycerol/.5 M sucrose), 3) cooled (0 degrees C) and 4) cryopreserved (-196 degrees C) oocytes was assessed after no incubation or a 24-h incubation. Survivability was judged by morphological appearance, trypan blue exclusion and fluorescein diacetate staining. Survival rate of control oocytes (90%; based primarily on morphological appearance of the cumulus) incubated 0 h was greater (P less than .05) than that of all other groups, whereas survival rate of -196 degrees C oocytes (57%) was less (P less than .05) than that of all other groups. However, vital staining of 0 degrees C and -196 degrees C oocytes showed 0% survival rate as evidenced by trypan blue uptake and lack of fluorescence. The cumulus cells surrounding oocytes that were stored at 0 degrees C or -196 degrees C survived freezing as evidenced by trypan blue exclusion and intense fluorescence. Similar differences among treatment groups were found for oocytes incubated 24 h. Exp. 2 examined the temperature at which oocytes became sensitive to cooling. Oocyte death occurred when oocytes were cooled to 15 degrees C or lower. These results demonstrate that pig oocytes at the germinal vesicle stage did not survive cooling to 15 degrees C or below. When assessing the viability of cryopreserved cumulus enclosed oocytes it is important to use vital stains in conjunction with morphological appearance. PMID- 2211411 TI - A review of the physiological significance of hypertonic body fluids on feed intake and ruminal function: salivation, motility and microbes. AB - Mechanisms exist in the ruminant to detect changes in osmolality and volume of plasma during feeding to maintain fluid and electrolyte homeostasis. Feed intake during a meal can be limited by the rise in osmolality of ruminal fluid, which is sensed in the wall of the rumino-reticulum. Ruminal microbes appear to be resilient to the short-term changes in ruminal fluid tonicity, but in vitro growth rates are inhibited when the tonicity of the culture medium is increased beyond physiological levels. Although mixing contractions of the rumen are not inhibited by the normal increases in tonicity of ruminal fluid, time to first rumination is increased. This aspect of motility requires further research. The tonicity of plasma increases toward the end of a large meal as a consequence primarily of absorption of VFA and Na+ from the rumen and fluid shifts into the gut. This hypertonicity is sensed centrally to inhibit parotid secretion by a reduction in the parasympathetic stimulation to the gland. Increases in animal production may result from future research directed toward developing ways of counteracting these negative effects of hypertonicity in body fluids on feed intake and ruminal function. PMID- 2211412 TI - Effects of intravenous infusion of high levels of potassium and sodium on mineral metabolism in sheep. AB - A metabolism trial was conducted with 18 crossbred (Finn x Dorset x Suffolk) wethers, fitted with indwelling jugular catheters and abomasal and ileal cannulas, to determine the effects of high levels of i.v.-infused K and Na on mineral metabolism. The wethers (40 kg) were fed 800 g daily of a 60% concentrate diet in two equal portions at 0800 and 1900. Six wethers were infused randomly with 19 g K+, six with 10.6 g Na+ (chloride salts) and the other six with physiological saline solution (1.2 g Na) per day. Potassium chloride or NaCl infusion had no effects on apparent absorption, retention, flow or partial absorption of Mg, Ca and P in the digestive tract compared with physiological saline infusion. With all treatments, Mg and Ca were absorbed proximal to the abomasal cannula. Magnesium was secreted into, whereas Ca and P were absorbed from, the small intestine. Phosphorus was secreted both in the stomach and large intestinal regions of the digestive tract. Major sites of K and Na absorption were the small and large intestines, respectively. Infusion of K increased (P less than .05) retention of K compared with Na infusion. Infusion of Na increased (P less than .05) excretion and retention of Na compared with K infusion. Serum minerals were not changed by K or Na infusion compared with saline. The results of this experiment indicate that the depressing effects of K on Mg absorption are not attributable to high levels of absorbed K, but rather to K present in the digestive tract prior to the small intestine. PMID- 2211413 TI - Effects of supplemental alfalfa hay on feed intake and digestion by Holstein steers consuming high-quality bermudagrass or orchardgrass hay. AB - Effects of level and frequency of supplementation with alfalfa (A) on feed intake and digestion by steers fed bermudagrass (B) or orchardgrass (O) were determined in two Latin square experiments. In Exp. 1, six Holstein steers (224 kg) were fed B (2.25% N; 71.4% NDF) or O (2.52% N; 64.3% NDF) with 0, 15 or 30% (DM) A (2.70% N; 44.0% NDF). Total DMI was 2.43, 2.72 and 2.85% BW for B and 2.98, 3.00 and 2.87% BW for O with 0, 15 and 30% A, respectively. Total DMI was affected by forage (P less than .05), A level (linear; P less than .06) and a forage x A level (linear) interaction (P less than .05). Digestible OM intake increased .42 (15%) and .67 kg (24%) with feeding of 15 and 30% A, respectively, for B, but for O, only dietary inclusion of 30% A elevated digestible OM intake (.14 kg and 4% increases). In Exp. 2, five Holstein steers (165 kg) were fed B (1.81% N; 78.6% NDF) alone or with A (2.76% N; 52.8% NDF). Morning meals consisted of ad libitum B (OA), .3% BW of A daily (.3A), .6% BW of A every 2nd d (.6A), .9% BW of A every 3rd d (.9A) or 1.2% BW of A every 4th d (1.2A). All steers received B in the afternoon ad libitum, and B was given in the morning when A was not fed. Total DMI was 2.31, 2.12, 2.12, 2.26 and 2.29% BW for OA, .3A, .6A, .9A and 1.2A, respectively (SE .049). Grass characteristics affected response in feed intake to legume supplementation. Frequency of dietary legume addition may alter feed intake. PMID- 2211414 TI - Forage composition and intake by steers grazing vegetative regrowth in low endophyte tall fescue pasture. AB - A grazing trial was conducted with six half-sib yearling Angus steers (average initial weight 281 kg) to quantitate nutrient composition and voluntary intake of vegetative regrowth forage in low-endophyte (Acremonium coenophialum Morgan-Jones and Gams) Kentucky-31 tall fescue (Festuca arundinacea Schreb.) pasture. A new .6 ha section in each of two 3.0-ha pastures (three steers/pasture) was clipped to a 5-cm height on five consecutive days to establish a series of plots that could be grazed continuously during 5-d test periods at uniform stages of vegetative regrowth; each period represented a specific regrowth stage (7, 14, 21, 28 and 35 d). Steers were conditioned by training them to graze to satiety while tethered with an adjustable-length rope to a 1-m galvanized steel post. Grazing time was limited to two sessions daily beginning at 0800 and 1400, and satiety was achieved after no more than 2.5 h of continuous grazing in each session. Forage DM availability was controlled by adjusting tether length and was set each day at 4% of steer BW. Fecal DM output was measured by chromic oxide dilution. A quadratic (P less than .05) effect of regrowth stage was observed for forage contents of NDF and ADF due to abrupt increases in both fractions at wk 5; values for ADL were unaffected by stage of forage regrowth. Forage contents of CP and ash showed a cubic (P less than .05) response to advancing stage of regrowth, with highest (23.6 and 11.0%, respectively) and lowest (14.7 and 9.1%, respectively) values for both fractions occurring at wk 1 and 5, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2211415 TI - Utilization of phosphorus and certain other minerals from swine waste and broiler litter. AB - Two trials were conducted with 15 wethers surgically equipped with duodenal and ileal cannulas to study the utilization of P, Ca, Mg, Cu, Fe and Zn from swine waste and broiler litter. For each trial, animals were fed a low-P basal diet until serum inorganic P averaged 5.5 mg/dl; then they were allotted at random to the following 50% DM ensiled diets: low-P basal, basal + swine waste, basal + broiler litter, basal + dicalcium phosphate and basal + soybean meal. Each trial consisted of a 7-d preliminary period, a 7-d collection of feces and urine and 6 d sampling of duodenal and ileal digesta and feces. Apparent P absorption was not different (P greater than .05) between sheep fed waste-supplemented diets (37%) and those fed the conventionally supplemented diets (28%). Phosphorus absorption, calculated by difference, tended (P less than .1) to be higher from the waste supplements (59%) than from dicalcium phosphate and soybean meal (37%). Less (P less than .05) Ca was absorbed from the waste diets (.62 g/d) than from the conventional diets (1.28 g/d). More (P less than .05) Cu (mg/d) was absorbed from the waste diets, but no difference was found when absorption was expressed as percentage of intake. Broiler litter and swine waste were good sources of available P and Mg for ruminants. PMID- 2211416 TI - Changes in ruminal and fecal particle weight distribution of steers fed coastal bermudagrass hay at four levels. AB - Samples of digesta from the ruminal upper strata (RUS) and feces (F) were taken from four ruminally cannulated steers fed Coastal bermudagrass hay (78% NDF) in the long form to evaluate the effects of feeding level and time postfeeding on particle breakdown. The experimental design was a 4 x 4 Latin square with 18-d periods. Treatments based on previous intakes were set at 50, 70, 90 and 110% (3.1, 4.4, 5.5 and 6.7 kg/d, respectively) of feed consumed per animal and fed at 12-h intervals. Samples were taken at 2, 6 and 12h postfeeding and wet-sieved. Dry matter weight distribution of total recovered particles was used to partition RUS and F digesta among percentages of large (greater than 4.0 mm), medium (greater than 4.0 and less than or equal to 1.0 mm), small (less than 1.0 and greater than or eual to .125 mm) and fine (less than .125 and greater than or equal to .0027 mm) particles. With increasing feeding level, the percentage of medium RUS particles increased linearly (P less than .02), whereas the percentage of fine RUS particles decreased linearly (P less than .01). Increased time postfeeding resulted in a linear decrease in the percentage of large RUS particles (P less than .01), a linear increase in the percentage of small RUS particles (P less than .01) and in a quadratic increase in the percentage of fine RUS particles (P less than .01). Percentage of medium RUS particles remained unchanged. Increasing feeding level resulted in linear increases in mean RUS (P less than .01) and F (P less than .02) particle sizes. Percentages of RUS and F material passing through a 1.0-mm sieve averaged 52.8 and 88.8%, respectively. Animal-to-animal variation in proportions of RUS and mixed reticuloruminal particles was not entirely removed by rumination and was still reflected in the percentages of F particles. Factors such as particle entrapment in the fiber mat, reticular sedimentation, changes in specific gravity, swelling and hydration capacity, reticuloruminal motility and amount of digesta exiting per contraction appear to be more important than particle size reduction in the regulation of the passage of digesta from the reticulorumen. PMID- 2211417 TI - Effects of zinc sulfate concentration and feeding frequency on ruminal protozoal numbers, fermentation patterns and amino acid passage in steers. AB - Effects of zinc sulfate (0 vs 1,142 ppm supplemental zinc from zinc sulfate) and feeding frequency (1 x vs 12x daily) on ruminal protozoa numbers, fermentation patterns and amino acid passage were investigated using four ruminally and abomasally cannulated mature Jersey steers in a 4 x 4 Latin square experiment. Steers (530 kg) were fed a 50:50 roughage:concentrate diet at 1.5 times their NEm requirement. Experimental periods were 14 d in duration; ruminal, abomasal and fecal samples were collected at 6-h intervals during the last 3 d of each period. Protozoa numbers tended to be lowest (1.82 x 10(6)/ml) in steers fed zinc 1 x and tended to be highest (3.83 x 10(6)/ml) in steers fed zinc 12 x daily (P less than .10). Frequent feeding decreased ruminal pH .24 units and increased total VFA 20.7%, ammonia 22.7% and ruminal digestion of dietary amino acids (AA) 61.6% (P less than .05). Zinc supplementation decreased ruminal digestion of dietary AA 35.8% (P less than .05) and the abomasal passage of bacterial OM and AA 21.2% (P less than .05) and increased ruminal output of amino acids as a percentage of intake 15.1% (P less than .05). Although it increased escape of dietary AA, zinc sulfate decreased postruminal passage of bacterial AA and resulted in a net negative effect on total postruminal AA passage as a percentage of intake. The effects of zinc on ruminal AA digestion may be more closely related to an interaction of zinc with dietary CP rather than to an effect of Zn on ruminal microbial populations. PMID- 2211418 TI - Influence of branched-chain fatty acid supplementation on voluntary intake, site and extent of digestion, ruminal fermentation, digesta kinetics and microbial protein synthesis in beef heifers consuming grass hay. AB - Four heifers (British x British; average BW 372 kg) cannulated at the rumen and duodenum and consuming a grass hay (fescue-orchardgrass) diet were used in a 4 x 4 Latin square and supplemented with four levels (0, 20, 40, and 60 g.head-1.d-1) of supplemental four- and five-carbon VFA (BCFA). Forage OM, ADF, NDF and N intakes and digestibilities were not affected (P greater than .10) by BCFA supplementation. Likewise, duodenal N (microbial, feed and ammonia) flows and microbial efficiency were not altered (P greater than .10) by BCFA supplementation. Neither particulate and fluid passage rate nor in situ rate of NDF digestion was affected (P greater than .10) by treatment. Ruminal pH, ammonia concentrations and total VFA concentrations were similar (P greater than .10) among treatments. Ruminal proportions of acetate and propionate were not affected (P greater than .10) by treatment; however, butyrate responded in a cubic (P less than .05) fashion to BCFA, with the lowest proportion of butyrate at the 40 g BCFA feeding level. A time x treatment interaction (P less than .05) was noted for isobutyrate, isovalerate and valerate proportions; they were increased as a function of BCFA dosage at 2 to 8 h postdosing. Supplemental four- and five carbon VFA had no effect on digestion and fermentation of grass hay. Supplementation of low-quality roughages with BCFA is not justified. PMID- 2211419 TI - Serum copper, zinc, calcium and phosphorus concentrations of calves stressed by bovine respiratory disease and infectious bovine rhinotracheitis. AB - The relationship between serum minerals and stress and(or) disease has not been fully evaluated in beef cattle. Two trials were conducted to determine the changes in serum Cu and Zn during market-transit stress and(or) disease. Two additional trials were conducted to determine the changes in serum Cu and Zn after inoculation with infectious bovine rhinotracheitis virus (IBRV), with one of the trials determining the changes in serum Ca and P. Trials 1 (n = 80) and 2 (n = 100) utilized calves that were handled through a normal market-transit system and transported 1,967 km to the feedlot. Trials 3 (n = 37) and 4 (n = 8) used calves that were sero-negative to IBRV and then challenged with 2.7 x 10(5) plaque-forming units of the virus. Serum samples were collected at specified intervals and serum minerals were measured for each trial. Serum Zn for morbid or IBRV-challenged calves was decreased by 34, 57, 29 and 15% (P less than .05) for the four trials, respectively, at peak morbidity. Serum Cu of morbid or IBRV challenged calves increased 5, 15, 40 and 33% for the four trials, respectively, at peak morbidity. Feed intakes were lower during morbidity for market-transit trials and after IBRV inoculation. Lower feed intake could partially explain the decrease in serum Zn; however, when feed intake was held constant, serum Zn concentration still decreased. Serum Zn decreased and serum Cu increased during market-transit morbidity or after IBRV. PMID- 2211420 TI - Comparison of soybean meal/sorghum grain, alfalfa hay and dehydrated alfalfa pellets as supplemental protein sources for beef cattle consuming dormant tallgrass-prairie forage. AB - Three experiments were conducted to compare soybean meal/sorghum grain (SBM/SG), alfalfa hay or dehydrated alfalfa pellets (DEHY) as supplemental protein sources for beef cattle grazing dormant range forage. In Exp. 1 (35-d digestion study), 16 ruminally cannulated steers were stratified by weight (average BW 259 kg) and assigned randomly within stratification to: 1) control, no supplement; 2) SBM/SG (25% CP) fed at .48% BW; 3) alfalfa hay (17% CP) fed at .70% BW; or 4) DEHY (17.4% CP) fed at .67% BW. Steers receiving protein supplements displayed at least a twofold increase in forage intake (P less than .10). In addition, steers supplemented with DEHY consumed approximately 15% more forage (P less than .10) than SBM/SG- or alfalfa hay-supplemented steers. Digestible DM intake (kg/d), however, was similar between alfalfa hay- and DEHY-supplemented steers and 20% greater (P less than .10) than for SBM/SG-supplemented steers. In Exp. 2, 82 mature, nonlactating Hereford x Angus cows (average BW 489 kg) were assigned randomly to SBM/SG, alfalfa hay or DEHY supplement treatments, which were replicated in three pastures. Cows supplemented with DEHY gained more weight (P less than .05) during the first 84 d of supplementation and displayed the least amount of weight loss at calving (d 127; P less than .05) and just prior to breeding (P less than .10). In contrast, calving interval (361 d) and pregnancy rate (94%) were unaffected (P greater than .10) by dam's previous supplemental treatment. In Exp. 3, one block (pasture) of cows from Exp. 2 was selected at random and grazing behavior was monitored during week-long periods in January and February. A treatment X time interaction (P less than .05) occurred for total time spent grazing; treatments did not differ in January, but cows supplemented with alfalfa hay spent less time grazing in the February grazing period. In conclusion, DEHY and alfalfa hay appear to be at least as effective as SBM/SG as a supplemental protein source for pregnant grazing cows when supplements are fed on an equal CP and ME basis. PMID- 2211421 TI - Inert plastics as indicators of physiological processes in the gastrointestinal tract of ruminants. AB - Various types of plastics with different physical properties have been useful in measuring rumination and passage events in the gastrointestinal tract (GIT) of ruminants. Plastic ribbons and monofilaments are available in different diameters, specific gravities and hardness and they can be cut to various lengths. Specific studies that are amenable to these materials include physical appetite control, regurgitation for rumination, passage from the rumen with or without rumination and passage through the entire GIT. Passage of particles through specific portions of the GIT can be measured in animals with various fistula preparations. The rumination of plastic ribbon in the rumen is similar to that of long forage. If the particle length is 7 cm or less, the particle can be regurgitated and produces normal rumination patterns. Movement of particles from one part of the rumen to another can be measured. Multiple sites can be studied in the same experiment by using particles of different colors. Isolating particles from ingesta or fecal residues usually starts with sieving to remove the small particles. Various subsequent separation schemes include flotation or sedimentation, air streams or acid digestion; when other methods fail, particles can be manually separated and counted. Plastic markers have several potential uses in ruminant research but they also have limitations. Because they are inert, they cannot undergo the hydration, density and size changes that occur with normal feed particles. PMID- 2211422 TI - Protein value of feather meal for ruminants as affected by blood additions. AB - In situ digestion and growth studies were conducted to determine the effects of adding blood to feather meal. In the in situ and digestion studies, soybean meal (SBM), blood meal (BM), feather meal (Fth) and two combinations of 55% raw blood and 45% feathers (RB + F) were used. Feathers and blood were combined either before or after steam hydrolysis of feathers. Ruminal escape protein of Fth was greater than that of SBM but less than that of BM (P less than .10) determined in situ after 12 h of incubation. Ruminal in situ protein digestion was lower (P less than .10) than for the other treatments (P less than .10) when blood was hydrolyzed with feathers. Total tract digestibility was similar (P greater than .10) for SBM, BM and the mixture of RB + F when the blood was not hydrolyzed. In the growth study, calves were supplemented with urea, SBM, BM, Fth or a combination of BM and Fth (BM + Fth; each supplied an equal portion of supplemental protein). The slope ratio technique was used to evaluate the protein sources. The most efficiently used protein sources were BM and BM + Fth compared to SBM and Fth (P less than .05). There was a numerical but not significant (P greater than .1) complementary effect of adding BM to Fth. Soybean meal and Fth had similar protein efficiencies (P greater than .20). Estimated amino acid flow to the small intestine based on in situ amino acid degradation suggested that the complementary effect observed for BM + Fth was due to BM supplying lysine and Fth providing sulfur amino acids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2211423 TI - Hydrolyzed feather meal as a protein source for growing calves. AB - Growth, digestion and in situ studies were conducted to determine the protein value of hydrolyzed feather meal (Fth) for growing ruminants. Dacron bags containing blood meal (BM), Fth, corn gluten meal (CGM) and soybean meal (SBM) were suspended in the rumen of two steers for 12 h to estimate escape protein. The escape protein value for Fth, 69.1%, was less than that for BM (82.8%) and CGM (80.4%; P less than .05) but greater than that for SBM (26.6%; P less than .05). Apparent protein digestion by lambs was similar (P greater than .10) for isonitrogenous diets containing urea (U), BM, Fth, CGM and SBM. Amino acid contents of the protein sources before vs after a 12-h ruminal in situ digestion were similar (P greater than .10). In a growth study, a basal diet of 80% ensiled corncobs and 20% alfalfa was fed to 60 individually fed crossbred steers (215 kg BW). Steers were supplemented with U, BM, Fth, 1/2 BM:1/2 Fth, 1/2 BM:1/2 CGM and 1/3 BM:1/3 Fth:1/3 CGM (protein basis). Protein sources were fed at 30, 45 and 60% of the supplemental N with urea supplying the remainder. Protein efficiency was calculated using the slope ratio technique. Protein efficiency was similar (P greater than .10) for BM- and Fth-supplemented calves. Protein efficiencies were similar (P greater than .10) for BM:CGM, BM:Fth and BM:Fth:CGM combinations. These data indicate the Fth is a digestible high escape protein source that is useful in diets for growing ruminants. PMID- 2211424 TI - Evaluation of various nitrogen supplements in starter diets for growing Holstein steers and their effects on ruminal bacterial fermentation in continuous culture. AB - Concurrent in vivo and in vitro studies were conducted to evaluate urea (U), soybean meal (SBM), ground soybeans (RAW), extruded soybeans (ES) or extruded soybeans plus urea (ES + U) as primary supplemental N sources in starter diets for Holstein steers. Three groups of 48 Holstein steers each were fed five different starter diets to 181 kg BW in three experimental periods over 2 yr. Average daily gains were similar (P greater than .05) for steers fed ES + U (1.12 kg), ES (1.08 kg) and SBM (1.09 kg) but lower (P less than .05) for those fed U (1.00 kg) or RAW (.97 kg) diets. Feed/gain was similar (P greater than .05) for ES-fed steers vs those fed other diets except U. From 181 to 477 kg, all steers were fed the same diet. Steers fed the RAW starter diet had the lowest (P less than .05) ADG for the entire period. The starter diets were used as substrates for ruminal microbial metabolism in eight dual-flow continuous culture fermenters. True OM digestion was higher and NDF and ADF digestion was lower (P less than .05) for the ES + U diet than for the ES diet. Dietary protein degradation was lowest (P less than .05) for the ES diet (64.4%). Total bacterial N flow was higher (P less than .05) with the ES + U, SBM and U diets than with the ES diet. Lysine flow was higher (P less than .05) for the ES + U diet than for all other diets except ES. Results of these experiments indicate that ES as a protected ruminal escape N source with or without added urea did not improve steer performance above that obtained from SBM in starter diets. PMID- 2211425 TI - Thirty or sixty percent milk replacer reduction for calves: effects on alfalfa hay intake and digestibility, digestive kinetics and ruminal fermentation. AB - Twelve artificially reared, male Holstein calves, ruminally cannulated at 53 d of age, were used in a split-plot design to study the effects of no milk replacer reduction (CON), or reduction by 30% (30R) or 60% (60R) of this value on alfalfa hay intake and digestibility, ruminal fermentation and digestive kinetics. Milk replacer reduction began at 53 d of age and continued until 135 d of age, after which no milk replacer was fed. All calves had ad libitum access to long-stemmed alfalfa hay from birth. Five collection periods were conducted at average calf ages of 72, 87, 108, 129 and 151 d. Reducing the amount of milk replacer fed resulted in a linear increase (P less than .05) in forage OM intake; however, total OM intake (forage + milk) was not different (P greater than .10) among milk reduction groups. Size of particles in feces exhibited quadratic effects in response to milk replacer reduction (P less than .05) but only in the small (less than 150 microns) size groupings. Ruminal pH and ammonia and individual VFA concentrations (except isobutyrate) were not altered by milk reduction (P greater than .10) but increased (P less than .01) with calf age. Milk replacer reduction had a quadratic effect (P less than .05) on fluid outflow rate from the rumen, increasing as milk replacer was reduced. Other fluid and particulate kinetic data, as well as NDF digestion rate and DM digestion showed no effects (P greater than .10) from milk replacer reduction but changed with calf age. Milk replacer reduction increased forage intake but had minimal effects on digestive variables evaluated, suggesting that intake of milk replacer by calves can be reduced by up to 60% without disturbing forage fermentation and passage. PMID- 2211426 TI - Comparative utilization of warm- and cool-season forages by cattle, sheep and goats. AB - The quality of different classes of forage hay (C3, C4 grasses and legumes) was determined in intake and digestibility trials with mature cattle, sheep and goats. For all nine hays, DM and NDF digestibility by cattle and goats was higher (P less than .05) than by sheep, with no differences due to forage class. Cattle had a higher (P less than .01) DM intake than sheep or goats averaged across forage (92.6 vs 65.8 and 68.6 g/kg BW.75); hay intake was highest on legume, with no difference between C3 and C4 grasses. Mean NDF intake by cattle was greater than by sheep or goats (58.7 vs 39.6 and 42.6 g/kg BW.75); NDF intake for all animal species decreased in the order C4 grass greater than C3 grass greater than legume. Particle passage rates did not differ (P greater than .05) with forage class but were higher (P less than .02) for sheep and goats than for cattle. Prefeeding ruminal DM fill values, determined by emptying, were 10.6, 15.0 and 19.9 g/kg BW1.0 for alfalfa, orchardgrass and switchgrass hays fed to cattle, and 11.2, 11.3 and 16.5 g/kg BW1.0 for the same hays fed to sheep. Estimated turnover times for DM and NDF were shorter (P less than .05) for sheep than for cattle; DM turnover was longer for switchgrass than for alfalfa and orchardgrass, with no forage differences in NDF turnover between these two animal species. Results show that goats were superior to sheep in NDF digestion. PMID- 2211427 TI - Regulation of digestive function in domestic livestock: intestinal absorption and exocrine secretions. PMID- 2211428 TI - Intestinal absorption of protein hydrolysis products: a review. AB - Many experimental techniques have allowed researchers to probe the fate of hydrolysis products from proteins in the small intestine. An overview of amino acid and peptide absorption from the small intestine is presented with attention given to historical perspectives that have led to current concepts. Speculation about nutritional significance of these processes is offered. Species differences exist in site of amino acid absorption. Numerous mechanisms are available for the transport of amino acids, including Na(+)-dependent carriers (energy-requiring), Na(+)-independent carriers and diffusion. The relative contribution each transport system makes to absorption is dependent on substrate concentration. Individual amino acids are not absorbed with equal efficiency; methionine usually is absorbed in the greatest proportion. There are interactions among amino acids for transports by specific transport systems. Small peptides (mostly di- and tripeptides) are absorbed from the small intestine more rapidly than are free amino acids; peptides are transported by systems independent of those responsible for transporting free amino acids. Evidence exists that the active transport of these peptides is via a proton gradient. Although the concept that peptides are absorbed intact into the circulation is not universally accepted, evidence supporting the possibility of tissue utilization of these small peptides is accumulating. PMID- 2211429 TI - [63rd general meeting of the Japan Leprosy Association. Abstracts]. PMID- 2211430 TI - The biofilm glycocalyx as a resistance factor. PMID- 2211431 TI - A high performance liquid chromatography system for the simultaneous assay of some antibiotics commonly found in combination in clinical samples. AB - Using a single reversed-phase HPLC column with a mobile phase of methanol and 100 mM phosphate buffer, concentrations of seven antibiotics (chloramphenicol, metronidazole, cefuroxime, cephalexin, ceftazidime, ampicillin and benzylpenicillin) which are commonly used clinically in combinations of two or more, can be assayed and results reported within one hour. No endogenous interference was detected in serum, urine or cerebrospinal fluid. The method was highly specific even in the presence of other drugs and metabolites commonly found in clinical samples and provides a rapid, simple technique suitable for use in routine microbiological practice. PMID- 2211432 TI - Influence of cefotaxime on microbial colonization resistance in healthy volunteers. AB - The influence of cefotaxime 1000 mg given intravenously bd on microbial colonization resistance was investigated in six healthy volunteers. Administration of cefotaxime allowed colonization of the bowel by a resistant challenge strain of Enterobacter cloacae in all volunteers. The faecal concentration of aerobic flora increased significantly in five of six volunteers. In one the numbers of Gram-negative bacilli, enterococci and yeasts also increased. In the other four the faecal concentration of enterococci and yeasts increased, but Gram-negative bacilli did not rise above pre-treatment level. It is concluded that cefotaxime impairs colonization resistance, although to a variable degree. Therefore the term 'selective decontamination' is not fully justified for prophylactic regimens that include cefotaxime. PMID- 2211434 TI - Resistance to aminoglycoside antibiotics in gram-negative bacilli and staphylococci isolated from blood. Report from a European collaborative study. The ESGAR Study Group (European Study Group on Antibiotic Resistance). AB - The incidence of resistance to gentamicin, tobramycin, amikacin and netilmicin was determined by the microdilution method in Mueller-Hinton broth among blood culture isolates consecutively collected in 37 laboratories in 14 European countries. The distribution of bacteria was similar in each laboratory, Escherichia coli and staphylococci predominating. Resistance levels varied between laboratories but they were higher to all four antibiotics in Southern Europe than in Central and Northern Europe. Aminoglycoside resistance was usually associated with production of aminoglycoside-modifying enzymes, ANT(2"), AAC (3) V, AAC (6')-I predominating in Gram-negative bacilli and APH (2") + AAC (6') and ANT (4')-I in staphylococci. PMID- 2211433 TI - Faecal excretion of ciprofloxacin after a single oral dose and its effect on faecal bacteria in healthy volunteers. AB - High concentrations of ciprofloxacin have been shown to persist in the faeces of volunteers for several days after a week of oral treatment with this drug, which was also found to have a prolonged effect on aerobic Gram-negative intestinal bacteria. To determine whether a shorter course of ciprofloxacin would have the same prolonged effect, we treated ten healthy adult volunteers with a single oral dose of 750 mg ciprofloxacin and found that this was not followed by any significant changes in the counts of anaerobes or streptococci, but that there was a mean decrease of 2.5 log10 cfu/ml in the counts of faecal Enterobacteriaceae, which lasted for a full week. We attributed this to the persistence of high faecal ciprofloxacin concentrations for several days in all the volunteers. We did not observe any significant increase in the MICs of ciprofloxacin for faecal Enterobacteriaceae, or any faecal overgrowth of staphylococci, fungi, Pseudomonas aeruginosa or Clostridium difficile. PMID- 2211435 TI - Monitoring of aminoglycosides. PMID- 2211436 TI - Invasive infections due to Haemophilus influenzae type b resistant to ampicillin and chloramphenicol. PMID- 2211438 TI - Lomefloxacin disc susceptibility criteria--a reappraisal. PMID- 2211437 TI - Ciprofloxacin versus amoxycillin/clavulanic acid in the treatment of urinary tract infections in general practice. PMID- 2211439 TI - In-vitro susceptibilities of Bacteroides gracilis, Fusobacterium mortiferum and F. varium to 17 antimicrobial agents. PMID- 2211440 TI - In-vitro sensitivity tests and in-vivo efficacy of cephalosporins against Bacteroides fragilis. PMID- 2211442 TI - Short course ciprofloxacin therapy for CAPD peritonitis. PMID- 2211441 TI - Reassessment of cefuroxime axetil for the treatment of recurrent urinary infections. PMID- 2211443 TI - Intra- and inter-specific transformation of Streptococcus pneumoniae to penicillin resistance. AB - Transformation studies were carried out with a penicillin susceptible (MIC 0.006 mg/l) laboratory strain of Streptococcus pneumoniae as recipient. Donor DNA was prepared from two clinical isolates of S. pneumoniae, four isolates of S. mitior and five isolates of S. sanguis. DNA from both isolates of S. pneumoniae generated penicillin-resistant transformants (MICs 0.03-2.0 mg/l). In addition, one isolate each of S. mitior and S. sanguis transformed the recipient to increased penicillin resistance, with MICs of 0.125 mg/l. DNA from the S. sanguis strain generated a transformant which showed a reduction in the penicillin binding affinity of penicillin-binding protein (PBP) 2B. DNA from a second S. mitior strain generated intermediately resistant (MIC 0.5 mg/l) transformants in a single transformation round. The PBP profiles of these transformants showed an apparent molecular size alteration of PBP 2B, corresponding to a PBP found in the donor strain, and PBP 1B was no longer detected. Isolates of S. pneumoniae may apparently develop penicillin resistance either intrinsically, by intragenetic transfer, or by transfer of penicillin resistance determinants from viridans streptococci. PMID- 2211444 TI - Activity of sub-minimal inhibitory concentrations of aspoxicillin in prolonging the postantibiotic effect against Staphylococcus aureus. AB - Aspoxicillin, a newly developed acylureido-penicillin with a long half-life in mouse serum of 55 min, induced postantibiotic effects (PAEs) against Staphylococcus aureus Smith of 1.7 h in vitro and 5.2 h in vivo in a thigh infection model in neutropenic mice. The long serum half-life meant that in order to evaluate the in-vivo PAE, it was necessary to examine the contribution of the drug at a sub-minimal inhibitory concentration (sub-MIC). Growth suppression by sub-MICs of aspoxicillin was examined in vitro using either previously unexposed bacterial cells or cells which had been pre-exposed to twice the MIC of aspoxicillin for 2 h. At each sub-MIC tested, the duration of growth suppression for pre-exposed cells was longer than that for unexposed cells. In an attempt to eliminate the sub-MIC effect in vivo, penicillinase was injected into mice at the time after administration when the aspoxicillin serum concentration approached the MIC. The in-vivo PAE decreased to 2.7 h when penicillinase was injected. It was concluded that aspoxicillin induced a PAE in vivo which was additional to the effect of sub-inhibitory residual drug, but that sub-MIC levels of the drug were simultaneously involved in suppressing bacterial regrowth after the drug concentration decreased below the MIC. Similar postantibiotic sub-MIC effects may also occur with other long half-life antibiotics. PMID- 2211445 TI - In-vitro activity of PD 117 596, a new quinolone, against bacterial isolates from cancer patients. AB - The in-vitro activity of PD117 596, a new 4-quinolone antimicrobial agent was compared with that of ciprofloxacin against 798 Gram-positive and Gram-negative distinct isolates from cancer patients. PD117 596 was found to have a broad antimicrobial spectrum with excellent activity against the Enterobacteriaceae (MIC90 0.03 mg/l) Acinetobacter spp. (MIC90 0.25 mg/l), Aeromonas spp. (MIC100 0.06 mg/l) and Pseudomonas spp. including Ps. aeruginosa (MIC90 0.5 mg/l). It was also extremely active against Gram-positive micro-organisms particularly Staphylococcus spp. (including methicillin-resistant and coagulase-negative isolates) Bacillus spp. and streptococci. PD117 596 had lower minimal inhibitory concentrations against most isolates tested than ciprofloxacin, the most active currently available 4-quinolone. PMID- 2211446 TI - The effects of single and combined antibiotics on the growth of Legionella pneumophila using time-kill studies. AB - The combinations of erythromycin with rifampicin, with ciprofloxacin or with amoxycillin, and ciprofloxacin plus rifampicin were tested by the time-kill curve method to assess their bactericidal activity against Legionella pneumophila. Rifampicin-resistant strains were found in broth cultures of the micro-organism even before exposure to the drug. In the presence of MBCs of rifampicin, the sensitive organisms were killed, allowing the resistant mutants to multiply. In broths containing both erythromycin and rifampicin, the rifampicin-resistant mutants were killed more rapidly than by erythromycin alone. In addition, erythromycin was effective in preventing the growth of amoxycillin- and ciprofloxacin-resistant organisms. Fortunately resistance to erythromycin was not detected by these time-kill studies. Thus for patients with severe forms of Legionnaires' disease, erythromycin should be combined with other more inhibitory drugs, such as rifampicin or ciprofloxacin, to enhance bactericidal activity. PMID- 2211447 TI - Influence of cefodizime on chemotaxis and the respiratory burst in neutrophils from diabetics. AB - The effect of cefodizime on the function in vitro of neutrophils from poorly controlled, non-insulin-dependent diabetics was demonstrated by the chemotactic index and by chemiluminescence. Without cefodizime treatment, the chemotactic index for diabetic neutrophils was significantly lower than that for healthy controls (1.0 +/- 0.1 vs 3.6 +/- 0.7; mean +/- S.E.M., P less than 0.01). When neutrophils were pretreated with cefodizime at 1 or 10 mg/l, cefodizime restored the chemotactic activity of diabetic neutrophils (1.0 +/- 0.1 vs 2.7 +/- 0.3, P less than 0.01), but did not affect the activity in healthy controls. Conversely, cefodizime at 100 mg/l had no enhancing effect on diabetic neutrophil chemotaxis, but decreased the chemotactic activity of healthy neutrophils (1.1 +/- 0.2 vs 3.6 +/- 0.7, P less than 0.01). A difference in neutrophil chemiluminescence was also found between diabetics and healthy subjects but no influence of cefodizime on chemiluminescence was noted in neutrophils from either diabetics or healthy subjects. PMID- 2211448 TI - Alterations to the penicillin-binding proteins in the Bacteroides fragilis group: a mechanism for non-beta-lactamase mediated cefoxitin resistance. AB - The penicillin-binding proteins (PBPs) of ATTC Type Strains of nine species of the Bacteroides fragilis group were visualized by gel electrophoresis and subsequent fluorography. Each species had a distinctive PBP pattern, although variation within species was seen. Generally, five PBPs could be visualized, ranging in molecular weight from approximately 40,000 to approximately 90,000. A laboratory-derived cefoxitin-resistant mutant of B. distasonis was compared with its wild type parent and cefoxitin-sensitive revertant. The fluorograph of the resistant mutant indicated a marked reduction of labelling to the PBP-1 complex as compared with the wild type and revertant. Cefoxitin-resistant clinical isolates of B. thetaiotaomicron and B. uniformis also showed changes to the PBP-1 complex, in comparison with sensitive strains. PMID- 2211449 TI - Antibacterial activity of cefpodoxime proxetil in a pharmacokinetic in-vitro model. AB - The antibacterial activity of cefpodoxime proxetil was studied in an in-vitro model simulating doses of 100, 200 and 400 mg. Strains of Klebsiella spp. Proteus mirabilis, Escherichia coli, Streptococcus pyogenes, and Haemophilus influenzae were effectively reduced by a dose of 200 mg. While for Esch. coli no dose activity relationship was observed--the maximal effect was achieved with a simulated dose of 100 mg--Staphylococcus aureus could be reduced effectively only by a simulated dose of 400 mg. The lower doses showed stepwise lower activities. Apart from broad spectrum beta-lactamases like SHV 2 or TEM 5 the presence of plasmid coded beta-lactamases in Esch. coli and H. influenzae did not affect the antibacterial activity of cefpodoxime proxetil. The results show that cefpodoxime was more active against Gram-negative bacteria than amoxycillin, and comparable activity to intramuscular cefotiam in the in-vitro model. PMID- 2211450 TI - The penetration of ceftriaxone into human brain tissue. AB - The cerebral penetration of ceftriaxone in patients who underwent surgery for cerebral tumours was investigated. Seventeen patients received 2 g of ceftriaxone given intravenously 2 to 13 h before blood and brain samples were taken. Antibiotic levels were determined by an agar-well diffusion method. Cerebral ceftriaxone concentrations ranged from 0.3 to 12 micrograms/g, with a mean value of 1.63 micrograms/g. These values were less than 2% of corresponding serum concentrations, but enough to inhibit 75% of bacterial strains recently isolated from brain abscesses in our unit. PMID- 2211451 TI - The penetration of roxithromycin into human skin. AB - The skin penetration of roxithromycin was studied in 27 surgical patients treated with 300 mg orally followed by three oral doses of 150 mg 12-hourly. Peak plasma and skin concentrations of 7.9 +/- 1.2 mg/l and 31.3 +/- 3.7 mg/kg occurred 2.5 and 4 h after last dosing respectively. The plasma and skin half-lives were 7.7 and 6.0 h, and the mean plasma and skin area under the curve values were 64.3 mg/l.h and 155.3 mg/kg.h. Skin/plasma concentration ratios were 4.9 +/- 0.5, 9.7 +/- 1.2, 7.6 +/- 0.8 and 5.9 +/- 1.1, at 3, 4, 5 and 6 h after last dosing respectively. These results demonstrate that roxithromycin achieves high levels in human skin. PMID- 2211452 TI - Pharmacokinetics of intravenous imipenem/cilastatin during intermittent haemofiltration. AB - The pharmacokinetics of a single iv dose of imipenem/cilastatin (500/500 mg) were studied during and after intermittent haemofiltration (IHF) treatment in six patients with chronic renal failure. The elimination half-lives of imipenem and cilastatin during the IHF treatment were almost identical, 1.4 +/- 0.3 and 1.5 +/ 0.3 h, respectively. Accordingly, approximately 75% of the given dose was eliminated during a 3-h IHF session. However, there was a great difference between the elimination half-lives of the two drugs in the post-treatment period, 3.4 +/- 1.0 and 16 +/- 10 h for imipenem and cilastatin, respectively. The haemofiltration clearance of imipenem was 134 +/- 41 ml/min and that of cilastatin 109 +/- 8 ml/min. On the basis of our results, we suggest that a supplementary dose of imipenem/cilastatin (500/500 mg) should be given directly after the IHF treatment. This dose should be the starting dose for a period of 12 h dosing intervals until the next IHF procedure. PMID- 2211454 TI - In-vitro tests of the functions of phagocytic cells and their interaction with antimicrobial agents: a critical view. PMID- 2211453 TI - Penicillin-induced post antibiotic effects on streptococci in vitro and in vivo. PMID- 2211455 TI - Antibacterial effect of meropenem and imipenem on Proteus mirabilis. AB - Phase-contrast microscopy, killing-curves and turbidimetric growth-curves were used in a comparative study of the antibacterial effects of a new carbapenem, meropenem (SM 7338) and imipenem on five strains of Proteus mirabilis. Despite the low MIC (0.2 mg/l) of imipenem for the five strains included in our study, the MBC remained relatively high (4.4 mg/l). During the first few hours of incubation, imipenem induced large lemon-shaped cells while the turbidity increased without substantial changes in culture viability. Later, most of the cell-wall deficient bacteria generated small spheroplasts until the antibiotic concentration exceeded 32 times the MIC. The MIC of meropenem was lower (0.03 mg/l) with an MBC (0.08 mg/l) very close to the MIC. Meropenem also induced large bodies but these cell-wall deficient bacteria did not generate small round bodies as observed with imipenem. In conclusion, imipenem produced in strains of Pr. mirabilis an amdinocillin-like change in cell morphology, responsible for the discrepancies observed between MIC and MBC. This effect was not observed with meropenem. PMID- 2211456 TI - Effects of supra- and sub-MIC benzylpenicillin concentrations on group A beta haemolytic streptococci during the postantibiotic phase in vivo. AB - A postantibiotic effect (PAE) in vivo was induced in group A streptococci established in a tissue cage model in rabbits. The bacteria were exposed to 10 x MIC of benzylpenicillin in tissue cage fluid (TCF) for 2 h. TCF was then aspirated, penicillin was eliminated by washing and the bacteria were transferred to tissue cages in other rabbits in order to study the in-vivo killing kinetics of streptococci in the postantibiotic phase. In these latter rabbits the concentration of benzylpenicillin in TCF corresponded to 10 or 0.3 x MIC. Bacteria not previously exposed to penicillin were used as controls. Streptococci in postantibiotic phase were killed as effectively after re-exposure to 10 x MIC in vivo as the growing controls. Although the concentration of penicillin fell below the MIC after 12 h, no regrowth was seen during the following 12 h in either culture. When only subinhibitory concentrations in TCF were used in the second phase, a killing of approximately 1 log10 cfu/ml was noted both in the previously exposed cultures and in controls. Both cultures started to multiply first after 6-7 h. PMID- 2211457 TI - The effect of cefuroxime axetil on the faecal flora of healthy volunteers. AB - The effect on the faecal flora of cefuroxime axetil, an oral ester of cefuroxime, was examined in ten healthy volunteers following a dose of 250 mg twice a day for 41/2 days. The mean blood concentration 2 h after the ninth dose was 3.6 mg/l and the urinary excretion was approximately 40% in 6 h and 50% in 24 h. Two volunteers developed mild diarrhoea and one candida vaginitis. Although there was variation between volunteers in the changes found in the faecal flora, the major effects were a reduction in the total anaerobic bacterial count, particularly where high levels of cefuroxime were present in the faeces and a significant decrease or elimination of strains of Enterobacteriaceae plus an increase in the streptococcal count. Six volunteers showed an increase in the candida count. Clostridium difficile was not isolated from any volunteer and toxin was not present in the two volunteers who developed diarrhoea. Four volunteers showed high levels of cefuroxime in the faeces on the fourth or fifth days of treatment. PMID- 2211458 TI - Resistance to beta-lactam antibiotics and ciprofloxacin in gram-negative bacilli and staphylococci isolated from blood: a European collaborative study. European Study Group on Antibiotic Resistance. AB - In 1987 and 1988 members of the European Study Group on Antibiotic Resistance collected 3440 consecutive isolates of Gram-negative bacilli (63%) and staphylococci (37%) from blood cultures and performed susceptibility testing by the microdilution method. The MICs of ampicillin and cefazolin for susceptible Gram-negative bacteria were 1-8 mg/l, of piperacillin less than or equal to 0.5-4 mg/l, of aztreonam, imipenem, cefotaxime and ceftazidime less than or equal to 0.125-1 mg/l and of ciprofloxacin less than or equal to 0.125-0.5 mg/l. For susceptible staphylococci the MICs of cefazolin were less than or equal to 0.5-8 mg/l, of cefotaxime 1-4 mg/l, of ceftazidime 4-16 mg/l, of imipenem and ciprofloxacin less than or equal to 0.125-1 mg/l. The antibiotic resistance rates varied between laboratories, being generally lower in northern Europe, except for imipenem, which showed uniform, low resistance rates. In Escherichia coli resistance to ampicillin, piperacillin and cefazolin could be seen to have increased since a previous survey. PMID- 2211460 TI - Post antibiotic effect of ofloxacin and the activity of Mg++. PMID- 2211459 TI - Plasmid-mediated beta-lactam resistance in pathogenic gram-negative bacteria isolated in south India. AB - A field study was undertaken at the Christian Medical College Hospital in Vellore, South India in 1984. Two hundred and eighty-four clinical isolates of enterobacteria were collected from patients with significant bacteriuria and their sensitivities to a series of beta-lactam antibiotics were determined. There was a very high incidence of beta-lactam resistance (ampicillin resistance greater than 80% and cephaloridine resistance greater than 65%) amongst these isolates. There was significant resistance to the combination of ampicillin and clavulanic acid but few of the isolates were resistant to cefuroxime or ceftazidime. Seventy seven per cent of the Escherichia coli isolates were resistant to ampicillin and 57% were resistant to cephaloridine. Most of the resistant Esch. coli isolates carried resistance genes for both ampicillin and cephaloridine which were transferable, either by direct conjugation or by mobilization with the X+ plasmid. Characterization of the R-plasmids revealed considerable diversity. Although the distribution of plasmid-mediated beta lactamases was broadly similar to those found in other surveys, three new beta lactamases were identified and atypically some of the Esch. coli isolates produced PSE beta-lactamases. PMID- 2211461 TI - Serum and atrial tissue concentrations of cefonicid and cefamandole in patients undergoing coronary artery bypass graft surgery. PMID- 2211462 TI - Meningeal diffusion of high doses of acyclovir given with probenecid. PMID- 2211463 TI - SDD and the novel extended-broad-spectrum beta-lactamases. PMID- 2211464 TI - The emergence of ciprofloxacin resistance in Salmonella typhimurium. PMID- 2211465 TI - The timer-logger-communicator gait monitor: recording temporal gait parameters using a portable computerized device. AB - A portable microprocessor-based device, the timer-logger-communicator (TLC), was adapted and connected to footswitches to monitor and record temporal gait parameters in 25 hemiplegic and 30 normal subjects. Controls walked at 1.36 m/s with symmetric gait. Hemiplegic subjects had a mean walking speed of 0.43 m/s, asymmetric gait, and varying proportions of time spent in each phase, consistent with previously reported gait parameters. Trends in objective gait measures more closely paralleled trends in functional ambulation classification than in Brunnstrom motor recovery stages. The TLC gait monitor is a useful instrument to measure temporal parameters of gait in the clinical setting. PMID- 2211466 TI - The Vocational Rehabilitation Index: a guide to accident victims' requirements for return-to-work assistance. AB - The Vocational Rehabilitation Index (VRI) is an easily administered, seven-item, ordinally scaled assessment, developed from analysis of variables associated with early return to work in a representative sample of 194 persons who received compensation for injuries at work or in road traffic accidents. The VRI discriminates between persons who return to work and those who do not. It can be used to identify, amongst non-returners, those whose return to work might be assisted by referral to rehabilitation. It may also indicate the kind of assistance that would be most helpful. PMID- 2211467 TI - Reacquisition of dressing skills after stroke. AB - A group of stroke patients were assessed over four occasions using the Nottingham stroke dressing assessment. A similar pattern of difficulty in dressing was found for both males and females. The consistency of ordering of problems was highly significantly correlated in each of the four assessments. PMID- 2211468 TI - Mobility after stroke: reliability of measures of impairment and disability. AB - This paper investigates the reliability of six measures of impairment and disability related to mobility after stroke: the Rivermead Motor Assessment (RMA, gross function subsection); gait speed (over 5 and 10 m); the motricity index (leg scores only); functional ambulation categories; sitting to standing (by observation); and mobility categories. Twenty-five patients who had suffered a stroke 2-6 years earlier leaving them with mobility disability were seen as part of a home-based physiotherapy trial. Assessments were made by three people on three occasions over 5 weeks. All six measures were reliable in statistical terms. A variation in gait speed of up to 25% and a difference of 3 points in the RMA were the actual limits of reliability. PMID- 2211469 TI - Determination of ellagitannins in extracts of oak wood and in distilled beverages matured in oak barrels. AB - A method is described for determination of ellagitannins in ethanol-water extracts of oak wood and in distilled alcoholic beverages matured in oak barrels. It is based on the combined ellagic acid content according to ellagitannin structure. Hydrolysis was carried out in the presence of hydrochloric acid under reflux in a 100 degrees C oil bath for 3 h. Total ellagic acid was thus determined by liquid chromatography (LC), and the free ellagic acid content present in the ethanol-water media was subtracted, the difference being the combined ellagic acid content corresponding to ellagitannins. A 5 micron C18 column was used with detection at 254 nm. The method is specific for ellagitannins, which is an advantage over other analytical techniques for overall evaluation of these substances extracted from wood. Results for spirits distilled from wine, grain, and sugarcane were highly variable. PMID- 2211470 TI - Survey of residues of organochlorine pesticides in some marketable Egyptian fish. AB - One hundred random samples representing 34 species of marketable fish were collected from 8 Egyptian governorates during the period March 1986 to March 1988 and were analyzed for the presence of some organochlorine pesticides. The results showed the predominance of beta-BHC and lindane at maximum levels of 435.30 and 59.00 micrograms/kg, respectively, for fish samples obtained from Damietta governorate. The corresponding levels of aldrin, and o,p'-DDT were 34.27 and 734.10 micrograms/kg, respectively, for fish from the Red Sea governorate. gamma Chlordane, p,p'-DDE, and p,p'-DDT were found in fish from Ismailia governorate at respective maximum levels of 36.17, 234.40, and 57.19 microgram/kg. Heptachlor was identified at 8.50 micrograms/kg in Port Said governorate fish and o,p'-DDE at 10.59 micrograms/kg in Suez governorate fish. Mirex, on the other hand, could not be detected in any of the samples investigated. PMID- 2211471 TI - Improved gas chromatographic method for determination of daminozide by alkaline hydrolysis and 2-nitrobenzaldehyde derivatization and survey results of daminozide in agricultural products. AB - An improved method was developed for the quantitative determination of daminozide. This new method combines the alkaline hydrolysis and distillation steps of the PAM II method for daminozide with the derivatization, cleanup, and gas chromatographic determination steps of the Wright method for unsymmetrical dimethyl hydrazine (UDMH). The minimum detectable level is 0.05 ppm. Recoveries range from 85 to 110% when daminozide is added at 0.1 to 1.0 ppm, and are generally 40% at the 0.05 ppm level. A variety of domestic and imported products were analyzed by this improved method and daminozide was detected in 33 of the 98 samples analyzed. Levels detected ranged from a trace amount to 0.80 ppm. The identity of UDMH hydrazone was confirmed by mass spectrometry in many samples, thus confirming the presence of daminozide. Two samples containing daminozide were analyzed independently by a second laboratory and the findings were closely duplicated. PMID- 2211472 TI - Liquid chromatographic determination of pindolol and related compounds in raw materials. AB - A liquid chromatographic method for the assay of pindolol and related compounds in the bulk drug has been developed. The method resolves 6 known and several unknown impurities from the drug and each other by using a nitrile column, an acetonitrile-sodium acetate buffer (35 + 65), and a UV detector set at 219 nm. Minimum quantifiable amounts of impurities are 0.02% or less relative to the drug. Ten lots of pindolol raw material were evaluated for purity and drug content. Total levels of impurities in these samples, quantitated against pindolol, ranged from about 0.03 to 0.24%. Assay results were within the range of 98.5 to 101.5%. PMID- 2211473 TI - Liquid chromatography-electrochemical detection of furazolidone and metabolite in extracts of incurred tissues. AB - One-day-old chicks were raised to maturity on a diet fortified with 0.0055% furazolidone. Analyses of tissue extracts by a liquid chromatographic electrochemical detection screening procedure for nitro-containing drugs disclosed, in addition to the parent drug, an unidentified metabolite in the liver and breast tissue of the mature birds sacrificed while on the fortified feed. No evidence of residues of the drug or metabolite was found in birds removed from the medicated feed 48 h prior to sacrifice. In view of the rapid in vivo and postmortem metabolism of the parent drug in liver tissue, the metabolite can serve as an alternative means of detecting furazolidone residues in chicken tissues. PMID- 2211474 TI - Confirmation of identity by gas chromatography/tandem mass spectrometry of sulfathiazole, sulfamethazine, sulfachloropyridazine, and sulfadimethoxine from bovine or swine liver extracts after quantitation by gas chromatography/electron capture detection. AB - Four sulfonamide veterinary drug residues were quantitated by electron-capture detection (ECD) after separation by gas chromatography (GC). The identities of sulfathiazole (ST), sulfamethazine (SM), sulfachloropyridazine (SCP), and sulfadimethoxine (SDM) were confirmed in bovine or swine liver residues by tandem mass spectrometry (MS/MS). Bovine or swine liver tissues were extracted by using either the Tishler or the Manuel-Steller cleanup. The methylated residues containing ST, SM, SCP, and SDM were separated by GC prior to MS/MS daughter ion analysis. Control tissue, control tissue fortified at 0.1 ppm, and incurred tissue residues at approximately 0.1 ppm were analyzed for these 4 sulfonamides. A Finnigan Model TSQ-46 operating in the chemical ionization mode was used to perform the MS/MS daughter ion experiments. The identities of all 4 sulfonamides were confirmed in a single GC/MS/MS analysis. PMID- 2211475 TI - Sensitive streptavidin-biotin enzyme-linked immunosorbent assay for rapid screening of chloramphenicol residues in swine muscle tissue. AB - A sensitive, competitive enzyme-linked immunosorbent assay (ELISA) for chloramphenicol (CAP) in swine muscle tissue has been developed. The ELISA is based on an earlier procedure. To improve sensitivity, different optimization procedures were investigated. The introduction of a streptavidin-biotin system and the use of a coating antigen with a lower CAP incorporation resulted in the most sensitive ELISA: the CAP concentration giving 50% inhibition decreased from 125 ng/mL to 3.0 ng/mL. This ELISA procedure was applied for a rapid screening of CAP residues in swine muscle tissue. The tissues were extracted with demineralized water. A concentrated phosphate-buffered saline solution was added to the filtered aqueous extract and this sample solution was directly submitted to the ELISA procedure. The results were compared to values obtained by analysis of a corresponding blank. This blank was prepared by treating a part of the aqueous sample solution with an immobilized monoclonal antibody preparation. This treatment was necessary because aqueous extracts of different swine muscle tissues showed a high variation in dose-response curves, probably caused by the complexity and variability of the matrix. In spiked tissues, the presence of CAP at concentrations of 10 micrograms/kg and higher can be easily demonstrated. PMID- 2211476 TI - Study of carbendazin residue accumulation on greenhouse and field-grown strawberries, after successive treatments with benomyl. AB - Benomyl, a systemic fungicide used in preharvest treatments to prevent Botrytis and other fungal diseases, metabolizes to carbendazim (MBC). A study was undertaken to determine if the total residues of MBC of greenhouse and field grown Douglas strawberries accumulate in fruits after successive fortnightly treatments with a commercial preparation of benomyl. Statistical analysis of the data obtained indicates that residues of MBC do not accumulate in fruits; on the contrary, they decrease over time. PMID- 2211477 TI - High-performance immunoaffinity chromatography for drug residue analysis. AB - High-performance immunoaffinity chromatography (IAC) is a potentially strong analytical tool for measurement of drug residues in various matrixes. Although the use of Immunoaffinity separations is not new, the application to drug residue analysis is in its infancy. The present paper discusses the production and purification of antibody, the preparation of columns, the theoretical basis of the analytical separation and elution, and variations of the analytical approach. PMID- 2211478 TI - Determination of nitrite in cured meats by ion-exclusion chromatography with electrochemical detection. AB - A rapid liquid chromatographic (LC) method was developed for a sensitive determination of nitrite in cured meats, using ion-exclusion chromatographic separation and electrochemical detection (IEC-EC). The current AOAC colorimetric method requires 2 h shaking in a steam bath to eliminate interference from reducing compounds such as ascorbic acid. In the present method, nitrite was analyzed in the presence of ascorbic acid without interference, and the extraction time was reduced to 1 min. The extracted nitrite was determined by ion chromatography using anion-exclusion/HS column and amperometric detector equipped with platinum or glassy carbon electrode operating at +1.0 V vs Ag/AgCl reference electrode. The detection limit was 1 ppb as NO2-. The recoveries of 50 ppm nitrite added to frankfurter and meat stick were 103 and 99.6%, respectively, with relative standard deviations less than 4%. The high speed, sensitivity, and selectivity make the new method a useful alternative to the AOAC colorimetric method. PMID- 2211479 TI - Spectrofluorometric determination of histamine in fish and meat products. AB - A method has been developed for spectrofluorometric determination of histamine in fish and meat products. After a perchloric extract is obtained from samples, histamine is extracted with n-butanol and transferred to hydrochloric acid. Finally, histamine is subjected to a condensation reaction with o-phthalaldehyde (OPT). The method was tested for lack of interference from other amines. Precision of the method in fish products was 6.60% CV; recovery was 96.50%. In meat products, precision was 5.42% CV; recovery was 96.20%. By analysis of variance (P = 0.05), no significant statistical differences were found for recovery values vs histamine content in both foods. PMID- 2211480 TI - Diagnostic data evaluation. Part VI. Data evaluation to establish product standards. AB - Cooked corned beef was studied to evaluate the feasibility of monitoring the product by means of chemical analysis. The protein fat-free value and the moisture:protein ratio were evaluated with respect to variability. The moisture:protein ratio was not as effective as the former because of the greater variability and the requirement for additional analyses. PMID- 2211481 TI - Comparative evaluation of commercially available aflatoxin test methods. AB - Five qualitative methods and 1 quantitative aflatoxin analytical method were compared with the Holaday-Velasco (HV) minicolumn and thin-layer chromatography (TLC) methods for corn in an evaluation involving 4 U.S. Department of Agriculture Federal Grain Inspection Service (USDA-FGIS) laboratories, 1 laboratory at the University of Georgia, and 1 laboratory at the University of Arizona. Samples analyzed included 1 set of artificially contaminated corn containing both aflatoxin B1 and B2 (ratio of B1:B2 of 92:8), 1 set of artificially contaminated corn containing only aflatoxin B1, and 1 set of naturally contaminated corn. Levels of total aflatoxin tested were 0, 10, 15, 20, 25, 30, and 40 ppb. Results of analysis of these samples with each method evaluated are reported. Chi-square analyses indicated that performance of the Afla-20-Cup, Aflatest, EZ-Screen, OXOID, and SAM-A methods was not statistically different from that of the HV minicolumn. Agri-Screen results were not statistically different from those obtained with TLC. PMID- 2211482 TI - Liquid chromatographic determination of acifluorfen in soil and water. AB - An analytical method based on the use of a liquid chromatograph equipped with a UV detector was developed for the determination of acifluorfen in soil and water. Acifluorfen was extracted from soil in methanol-0.10N NaOH (80 + 20 v/v) and from water by partition with dichloromethane. Solvent partitioning and solid-phase extraction were used to separate acifluorfen from major interfering sample components. Average recoveries from soil at 1, 0.1, and 0.01 ppm fortification levels were 95.1 +/- 3.4, 92.6 +/- 2.9, and 73.9 +/- 3.0%, respectively. Recoveries from water spiked at levels from 0.01 to 1 ppm averaged 96.5 +/- 5.4%. Method limits of detection were 0.006 ppm in soil and 0.003 ppm in water. PMID- 2211483 TI - Cigarette smoke composition. Part 1. Limitations of FTC method when applied to cigarettes that heat instead of burn tobacco. AB - The design of a new cigarette that heats rather than burns tobacco calls for modifications to the Federal Trade Commission (FTC) method for analytical smoking. These changes include eliminating sample conditioning at 75 degrees F and 60% RH, exercising greater care in lighting cigarettes, and smoking cigarettes to self-extinguishment rather than to a predetermined butt length as a measure of complete consumption. By several gross analytical measures, smoke condensate from the new cigarette differs substantially from that of tobacco burning cigarettes. This is inferred from the lack of coloration of smoke condensate collected on Cambridge filters. Elemental analysis demonstrates reduced carbon and nitrogen content concurrent with increased hydrogen. Thermogravimetric analysis shows almost quantitative weight loss at Tmax = 220 degrees C. Ultraviolet (UV) spectrophotometric analysis shows greatly reduced levels of tobacco-derived smoke components and qualitative differences in chemical entities being measured. By design, the heat required for smoke formation is supplied by a carbon heat source embedded in the cigarette tip. Tobacco contained in the cigarette is not burned and is exposed to temperature less than 300 degrees C. Thus, it is apparent (1) that smoke from the new cigarette contains little or no "tar" as tar is classically defined, and (2) that the FTC method even as modified to account for cigarette design differences is appropriate only for determination of nicotine and carbon monoxide yielded from this cigarette. PMID- 2211485 TI - Enzymatic-spectrophotometric method for determination of cholinesterase activity in whole blood: collaborative study. AB - Ten collaborating laboratories assayed 4 blind duplicate pairs of whole bovine blood for cholinesterase activity. The 4 sample pairs ranged from normal (100%) to severely organo-phosphorus-inhibited (less than 10%) activity. Collaborators also received commercially available human lyophillized serum as an external control and a chromate solution to evaluate spectrophotometer performance. The Ellman kinetic assay was performed on a 1:1000 dilution of the whole blood in pH 8.0 phosphate buffer. The method monitors the increase in absorbance at 412 nm caused by formation of 5-thio-2-nitrobenzoic acid (yellow reaction product). Repeatability standard deviations (RSDr) ranged from 4.30 to 14.2%; reproducibility standard deviations (RSDR) ranged from 6.99 to 19.3%. The lower limit of detection was estimated to be 0.10 mumole/mL/min. The method has been approved interim official first action by AOAC. PMID- 2211484 TI - Cigarette smoke composition. Part 2. Method for determining major components in smoke of cigarettes that heat instead of burn tobacco. AB - A method is described for determining major constituents in the smoke of a cigarette that heats, but does not burn, tobacco. Dual, simultaneous separations are performed in a single gas chromatographic oven to determine water, glycerol, nicotine, and propylene glycol in a rapid and cost-effective manner. A materials balance of new cigarette smoke total particulate matter was attempted from both Cambridge filter and electrostatic precipitation smoke collection data. Serious deficiencies were found when Cambridge filter smoke collection was applied for this purpose. Electrostatic precipitation smoke collection eliminated these problems. The data obtained by electrostatic precipitation smoke collection indicate that water, glycerol, nicotine, and propylene glycol make up about 94% of new cigarette smoke total particulate matter. PMID- 2211486 TI - Flame atomic absorption spectrometric determination of serum zinc: collaborative study. AB - A method for determining serum zinc concentrations was collaboratively studied by 9 laboratories. Serum samples in polypropylene tubes are directly diluted with 0.03% Brij 35, and zinc is determined by flame atomic absorption spectrophotometry (AAS). A certified standard reference material serves as an external control. Repeatability relative standard deviations (RSDr) were 1.2 and 11.4% and reproducibility relative standard deviations (RSDR) were 6.1 and 12.9% for serum zinc concentrations of 6.36 and 0.63 micrograms/mL, respectively. The method has been approved interim official first action by AOAC. PMID- 2211487 TI - In vitro assay for protein digestibility: interlaboratory study. AB - True protein digestibilities of 17 protein sources were estimated by 6 laboratories using an in vitro, 3-enzyme digestion system in a pH stat. Samples from animal, vegetable, and mixed food sources were freeze-dried (if not already dried), ground, mixed, and shipped to each collaborator along with a sodium caseinate standard and trypsin, chymotrypsin, and peptidase. The uptake of titrant during enzymatic digestion was used to calculate estimates of digestibility. Digestibilities ranged from 100% for casein to 89.9% for whole wheat cereal. Mean relative standard deviations for repeatability were 1.4% for rolled oats and less than 1% for the remaining 16 samples. Mean relative standard deviations for reproducibility ranged from 5.0 to 0.8%; values were less than 2.5% for 13 of the 17 samples. PMID- 2211488 TI - Determination of taurine in infant formulas using ultrafiltration and cation exchange chromatography. AB - A fast and simple method for determination of taurine in infant formulas has been developed. The sample preparation uses disposable ultrafiltration cartridges to remove protein and clarify the sample. Hydrolysis is avoided, simplifying the procedure and increasing efficiency. One mL sample is centrifuged in a cartridge for 45 min. The filtrate is diluted with pH 2.2 citrate buffer and injected into a high performance amino acid analyzer. A cation-exchange column (sodium phase) is used with a single buffer eluant and an isocratic chromatographic program. Colorimetric detection is performed following post-column ninhydrin reaction. Chromatographic resolution from other ninhydrin-positive compounds is excellent. Average recoveries for 3 levels of spike for various products were 100-102%. Precision is 1-3% RSD, depending on product. Linearity, specificity, and ruggedness are excellent. The method is applicable to quality control testing of milk-based, soy-based, and prehydrolyzed protein-based infant formulas in the ready-to-use, concentrate, and powder forms. A variety of commercially available infant formulas from different manufacturers were analyzed and all were found to contain taurine levels comparable to human milk. Some human milk and cow's milk samples were also analyzed and results compare well with literature values. PMID- 2211489 TI - Determination of biphenyl residues in citrus fruit by derivative infrared spectrophotometry. AB - A method for determination of biphenyl residues in whole citrus fruit is described. The mascerated fruit was distilled in an acid medium, the distillate was extracted with cyclohexane, and biphenyl was determined in the extract using various measures obtained by first and second derivative infrared (IR) spectrophotometry. Calculations were performed by PE680 and SNGLE programs on data obtained using a Perkin-Elmer Model 3600 data station. The relative precision of the determinations at 70 ppm was 1.8 to 2.0%; the detection limit was 5 ppm in all measurements, and recovery of spiking concentrations of 20 to 80 ppm ranged from 90.2 +/- 5.5% (for the amplitude of the 739 cm-1 peak of the first derivative) to 97.5 +/- 2.0% (for the trough-to-peak difference from the 737 cm-1 minimum to the 743 cm-1 maximum of the second derivative. PMID- 2211490 TI - The prevalence and predictors of bronchial hyperreactivity in children and adolescents. PMID- 2211491 TI - The prevalence of predictors of bronchial hyperreactivity in children and adolescents. PMID- 2211493 TI - Breathing patterns in asthmatic children during attack. AB - Breathing patterns in asthmatic children during attack were studied using multielectrode impedance pneumography. A great number of respiration patterns were analyzed by a personal computer. During severe attacks, a pattern of prolonged expiratory time was noted. Inspiratory time, however, did not change, regardless of the severity of the asthmatic attack. No remarkable changes in breathing patterns were recognized during mild attacks. It was, therefore, considered that breathing patterns remained essentially unchanged except in cases of severe asthmatic attacks. PMID- 2211492 TI - Ethylenediamine-induced late asthmatic responses. AB - We report two asthmatics working in the same factory who exhibited late asthmatic responses (LAR) to ethylenediamine (EDA) vapor. After several months of exposure to EDA, both patients developed productive coughing, wheezing, and dyspnea. Provocative inhalation tests using EDA evoked LAR in both patients, but it did not evoke any asthmatic symptoms in healthy subjects. IgE antibodies to EDA examined by intracutaneous and P-K tests were detected. It appears that, in these two cases, LAR are mainly due to immediate-type allergic reactions. PMID- 2211494 TI - Continuous adventitious lung sounds. AB - Recent research has increased the still limited understanding about the generation of continuous adventitious lung sounds. These sounds all have a definite pitch, such as in stridor and wheezing. With the use of waveform analysis, one can examine more closely the relationship between what is heard and the pathophysiology causing the sound. Clinical examples are given to show the utility and limitations of current lung sounds analysis techniques. PMID- 2211495 TI - Regulatory interactions between phospholipid synthesis and DNA replication in Caulobacter crescentus. AB - Several Caulobacter crescentus mutants with lesions in phospholipid biosynthesis have DNA replication phenotypes. A C. crescentus mutant deficient in glycerol 3 phosphate dehydrogenase activity (gpsA) blocks phospholipid synthesis, ceases DNA replication, and loses viability in the absence of a glycerol phosphate supplement. To investigate the interaction between membrane synthesis and DNA replication during a single cell cycle, we moved the gpsA mutation into a synchronizable, but otherwise wild-type, strain. The first effect of withholding supplement was the cessation of synthesis of phosphatidylglycerol, a major component of the C. crescentus membrane. In the absence of glycerol 3-phosphate, DNA replication was initiated in the stalked cell at the correct time in the cell cycle and at the correct site on the chromosome. However, after replication proceeded bidirectionally for a short time, DNA synthesis dropped to a low level. The cell cycle blocked at a distinct middivision stalked cell, and this was followed by cell death. The "glycerol-less" death of the gpsA mutant could be prevented if the cells were treated with novobiocin to prevent the initiation of DNA replication. Our observations suggest that the processivity of C. crescentus replication requires concomitant phospholipid synthesis and that cell death results from incomplete replication of the chromosome. PMID- 2211496 TI - Trigger factor depletion or overproduction causes defective cell division but does not block protein export. AB - Trigger factor is an abundant cytosolic protein of Escherichia coli which can stabilize proOmpA for in vitro translocation across inner membrane vesicles. The gene encoding E. coli trigger factor was isolated and sequenced, allowing construction of strains in which the expression of trigger factor is readily regulated. We found no defect in the in vivo rate of synthesis or secretion of proOmpA in trigger factor-depleted cells. The primary physiological defect in trigger factor-depleted or -overproducing cells is an enrichment of filamented cells. Filamentation of the trigger factor-overproducing strain is suppressed by a multicopy plasmid expressing the essential division gene ftsZ, suggesting that trigger factor has an important role in cell division. PMID- 2211497 TI - Sequence and analysis of the rpoN sigma factor gene of rhizobium sp. strain NGR234, a primary coregulator of symbiosis. AB - We report the nucleotide sequence of the rpoN gene from broad-host-range Rhizobium sp. strain NGR234 and analyze the encoded RPON protein, a sigma factor. Comparative analysis of the deduced amino acid sequence of RPON from NGR234 with sequences from other gram-negative bacteria identified a perfectly conserved RPON box unique to RPON sigma factors. Symbiotic regulatory phenotypes were defined for a site-directed internal deletion within the coding sequence of the rpoN gene of Rhizobium strain NGR234: they included quantitative nodulation kinetics on Vigna unguiculata and microscopic analysis of the Fix- determinate nodules of V. unguiculata and Macroptilium atropurpureum. RPON was a primary coregulator of nodulation and was implicated in establishment or maintenance of the plant synthesized peribacteroid membrane. Phenotypes of rpoN in Rhizobium strain NGR234 could be grouped as symbiosis related, rather than simply pleiotropically physiological as in free-living bacteria such as Klebsiella pneumoniae and Pseudomonas putida. PMID- 2211498 TI - Characterization of a promoter and a transcription terminator of Spiroplasma melliferum virus SpV4. AB - Spiroplasma virus 4 (SpV4) is an isometric virus with single-stranded, circular DNA infecting the helical mollicute Spiroplasma melliferum, a honeybee pathogen. Previous studies in our laboratory led to the determination of the base sequence of the SpV4 DNA. Nine open reading frames and three promoterlike sequences (P1, P2, and P3) were identified. An inverted repeat leading to the formation of a hairpin structure on the transcription product was also found and predicted to be a transcription terminator (T). We have now studied the in vivo transcription of the SpV4 genome by Northern (RNA) blot analysis of the total RNAs extracted from SpV4-infected spiroplasma cells. Transcripts of 7.8, 4.4, 3.4, and 2.7 kilobases (kb) were detected. The 3.4-kb RNA was the major transcript. The 5' and 3' ends of this transcript were determined by S1 mapping and primer extension. Characterization of the 3' end by S1 mapping showed that the 3.4-kb transcript terminates within the stretch of uridine residues following the hairpin structure of terminator T. Characterization of the 5' end by S1 mapping indicated that transcription proceeds from a newly recognized promoter, P0, located 36 nucleotides upstream of P1. Primer extension resulted in two cDNA signals. The short cDNA was probably a primer extension artifact due to the presence of a hairpin structure on the transcript. When reverse transcriptase stopped at this hairpin or read through, the short or the long cDNA, respectively, was obtained. The size of the long cDNA identified P0 as the transcription promoter. Promoter P0 was also shown to be functional in Escherichia coli. Indeed, when inserted upstream of the chloramphenicol acetyltransferase gene of a promoter selection vector, it promoted transcription of this gene. As in the case of S. melliferum, two cDNAs were obtained by primer extension, the longer cDNA identifying P0 as the promoter. PMID- 2211499 TI - Interaction between the min locus and ftsZ. AB - In Escherichia coli, distinct but similar minicell phenotypes resulting from mutation at the minB locus and increased expression of ftsZ suggested a possible interaction between these genes. A four- to fivefold increase in FtsZ resulting from increased gene dosage was found to suppress the lethality of minCD expressed from the lac promoter. Since increased MinCD did not affect the level of FtsZ, this suggested that MinCD may antagonize FtsZ to inhibit its cell division activity. This possibility was supported by the finding that alleles of ftsZ isolated as resistant to the cell division inhibitor SulA were also resistant to MinCD. Among the ftsZ(Rsa) alleles, two appeared to be completely resistant to MinCD as demonstrated by the lack of an effect of MinCD on cell length and a minicell phenotype observed in the absence of a significant increase in FtsZ. It was shown that SulA inhibits cell division independently of MinCD. PMID- 2211500 TI - Purification of the Escherichia coli purine regulon repressor and identification of corepressors. AB - The Escherichia coli pur regulon repressor protein was overproduced in a phage T7 expression system. The overexpressed repressor constituted approximately 35% of the soluble cellular protein. Pur repressor was purified to near homogeneity by two chromatographic steps. Hypoxanthine or guanine was required for binding of purified repressor to purF operator DNA. Apparent dissociation constants of 3.4 nM were determined for binding of holorepressor to purF operator and of 1.7 and 7.1 microM were determined for aporepressor interaction with guanine and hypoxanthine, respectively. A requirement for hypoxanthine or guanine for conversion of aporepressor to holorepressor in vitro supports the earlier report (U. Houlberg and K.F. Jensen, J. Bacteriol. 153:837-845, 1983) that these purine bases are involved in regulation of pur gene expression in Salmonella typhimurium and confirms that hypoxanthine and guanine are corepressors. PMID- 2211502 TI - Mechanism of enhancement of microbial cell hydrophobicity by cationic polymers. AB - Polycationic polymers have been noted for their effects in promoting cell adhesion to various surfaces, but previous studies have failed to describe a mechanism dealing with this type of adhesion. In the present study, three polycationic polymers (chitosan, poly-L-lysine, and lysozyme) were tested for their effects on microbial hydrophobicity, as determined by adhesion to hydrocarbon and polystyrene. Test strains (Escherichia coli, Candida albicans, and a nonhydrophobic mutant, MR-481, derived from Acinetobacter calcoaceticus RAG 1) were vortexed with hexadecane in the presence of the various polycations, and the extent of adhesion was measured turbidimetrically. Adhesion of all three test strains rose from near zero values to over 90% in the presence of low concentrations of chitosan (125 to 250 micrograms/ml). Adhesion occurred by adsorption of chitosan directly to the cell surface, since E. coli cells preincubated in the presence of the polymer were highly adherent, whereas hexadecane droplets pretreated with chitosan were subsequently unable to bind untreated cells. Inorganic cations (Na+, Mg2+) inhibited the chitosan-mediated adhesion of E. coli to hexadecane, presumably by interfering with the electrostatic interactions responsible for adsorption of the polymer to the bacterial surface. Chitosan similarly promoted E. coli adhesion to polystyrene at concentrations slightly higher than those which mediated adhesion to hexadecane. Poly-L-lysine also promoted microbial adhesion to hexadecane, although at concentrations somewhat higher than those observed for chitosan. In order to study the effect of the cationic protein lysozyme, adhesion was studied at 0 degree C (to prevent enzymatic activity), using n-octane as the test hydrocarbon. Adhesion of E. coli increased by 70% in the presence of 80 micrograms of lysozyme per ml. When the negatively charged carboxylate residues on the E. coli cell surface were substituted for positively charged ammonium groups, the resulting cells became highly hydrophobic, even in the absence of polycations. The observed "hydrophobicity" of the microbial cells in the presence of polycations is thus probably due to a loss of surface electronegativity. The data suggest that enhancement of hydrophobicity by polycationic polymers is a general phenomenon. PMID- 2211501 TI - Escherichia coli sec mutants accumulate a processed immature form of maltose binding protein (MBP), a late-phase intermediate in MBP export. AB - Protein translocation across the Escherichia coli cytoplasmic membrane may consist of several temporally or topographically distinct steps. Although early events in the translocation pathway have been characterized to some extent, the mechanisms responsible for the trans-bilayer movement of a polypeptide are only poorly understood. This article reports on our attempts to dissect the translocation pathway in vivo. A processed form of maltose-binding protein (MBP) was detected in the spheroplasts of secY and secA temperature-sensitive mutant cells that had been pulse-labeled at the permissive temperature (30 degrees C). This species of molecule was found to have an electrophoretic mobility identical to that of the mature MBP, but a considerable fraction of it was inaccessible to externally added protease. It had not attained the protease-resistant conformation characteristically observed for the exported mature protein. The radioactivity associated with this species decreased during chase and was presumably converted into the exported mature form, a process that required energy, probably the proton motive force, as demonstrated by its inhibition by an energy uncoupler. The spheroplast-associated processed form was more predominantly observed in the presence of a low concentration of chloramphenicol. A similar intermediate was also detected for beta-lactamase in wild-type cells. These results suggest that in a late phase of translocation, the bulk of the polypeptide chain can move through the membrane in the absence of the covalently attached leader peptide, and the secA-secY gene products are somehow involved in this process. We termed the processed intermediates processed immature forms. PMID- 2211503 TI - Transcriptional analysis of the promoter region of the Pseudomonas putida branched-chain keto acid dehydrogenase operon. AB - Branched-chain keto acid dehydrogenase is a multienzyme complex produced by Pseudomonas putida when it is grown in a minimal medium containing branched-chain amino acids. A 1.87-kilobase (kb) DNA fragment was cloned and sequenced which contained 0.24 kb of the E1 alpha structural gene and 1.6 kb of upstream DNA. There were 854 base pairs (bp) of noncoding DNA upstream of bkdA1, the first gene of the bkd operon, and 592 bp between the transcriptional and translational starts. The G + C content of the noncoding region was 56.7% compared with 65.2% for all the structural genes of the operon. A partial open reading frame was found on the strand opposite that of the bkd operon beginning at base 774. When the bkd promoter was cloned into the promoter probe vector pKT240, streptomycin resistance was obtained in P. putida but not Escherichia coli with the promoter in both orientations, which indicates either that the bkd promoter is bidirectional or that there are two promoters in this region. A series of ordered deletions on both sides of the proposed site of the start of transcription revealed that almost 700 bp upstream of the start of translation were required for expression. Streptomycin resistance was also obtained in an rpoN mutant of P. putida KT2440 containing constructs with the intact bkd promoter, indicating that the bkd operon does not require the rpoN sigma factor for expression. Another construct containing the bkd promoter, bkdA1, and bkdA2 in pKT240 was used to transform P. putida JS113, a mutant which was unable to produce the E1 subunits of the branched-chain keto acid dehydrogenase. In this case, very high inducible expression of the bkd operon was obtained. PMID- 2211504 TI - Changes in fine structure and polypeptide pattern during development of Holospora obtusa, a bacterium infecting the macronucleus of Paramecium caudatum. AB - The development of the bacterium Holospora obtusa, which infects the macronucleus of Paramecium caudatum, was investigated in the course of a new infection from the infectious form into the reproductive form and vice versa. In parallel with a complete structural reorganization of the bacterium, the protein pattern changed gradually in this development. During the differentiation of the infectious form into the reproductive form, the voluminous periplasm was gradually reduced and the cytoplasm expanded, until the entire bacterium was filled by the cytoplasm. At this stage the long cell divided into five to seven short cells and thereby established the reproductive form, the main stage of the bacterium being maintained and multiplying in the host nucleus. In parallel with the reduction of the periplasm, some of the main proteins of the infectious form gradually disappeared in the electrophoresis pattern; some proteins disappeared earlier than others. Simultaneously, other proteins appeared and gradually became more prominent in the pattern of the developing reproductive form. In the reverse development, when the reproductive form differentiated into the infectious form, the bacterium grew longer, the cytoplasm was condensed, and electron-dense material was deposited in the extending periplasmic space. In parallel with this morphological development, the polypeptide pattern reverted to that of the infectious form. PMID- 2211505 TI - Cloning of wild-type Pseudomonas solanacearum phcA, a gene that when mutated alters expression of multiple traits that contribute to virulence. AB - Pseudomonas solanacearum undergoes a spontaneous mutation that pleiotropically reduces extracellular polysaccharide (EPS) production, endoglucanase activity, and virulence and increases motility. We refer to the process that coordinately affects these traits as phenotype conversion (PC) and the resulting mutants as PC types. Previous research with the wild-type strain AW1 suggested that inactivation of a single locus could mimic phenotype conversion (T. P. Denny, F. W. Makini, and S. M. Brumbley, Mol. Plant-Microbe Interact. 1:215-223, 1988). Additional Tn5 mutagenesis of AW1 generated three more mutants (AW1-81, AW1-82, and AW1-84) that were indistinguishable from the PC type and one slightly leaky mutant (AW1-87); all four had single insertions in the same 4.0-kilobase (kb) EcoRI fragment that were responsible for the PC-like phenotype. Another insertion mutant, AW1-83, which lacks an insertion in this 4.0-kb fragment, resembled the PC type except that it was reversibly induced to produce wild-type levels of EPS when cultured adjacent to AW1. The wild-type region containing the gene that controls traits affected by phenotype conversion in AW1, designated phcA, was cloned on a 2.2-kb DNA fragment that restored all the phcA::Tn5 mutants and 11 independent spontaneous PC-type derivatives of AW1 to wild-type status. Homology with the phcA region was found in diverse wild-type strains of P. solanacearum, although restriction fragment length polymorphisms were seen. No major DNA alterations were observed in the phcA homologous region of PC types from strain AW1 or 82N. PC types from 7 of 11 conjugal strains of P. solanacearum were restored to EPS+ by phcA from AW1; however, only some PC types of strain K60 were restored, whereas others were not. We believe that a functional phcA gene is required to maintain the wild-type phenotype in P. solanacearum, and for most strains phenotype conversion results from a loss of phcA gene expression or the function of its gene product. PMID- 2211506 TI - Regulation of fructose metabolism and polymer synthesis by Fusobacterium nucleatum ATCC 10953. AB - Energy for the anaerobic growth of Fusobacterium nucleatum ATCC 10953 can be derived from the fermentation of sugar (fructose) or amino acid (glutamate). During growth on fructose, the cells formed large intracellular granules which after extraction yielded glucose by either acid or enzymatic hydrolysis. The endogenous polymer was subsequently metabolized, and after overnight incubation of the cells in buffer, the glucan granules were no longer detectable by electron microscopy. Anaerobically, washed cells grown previously on fructose fermented this sugar to a mixture of lactic, acetic, and butyric acids, and little intracellular glucan was formed. Aerobically, the cells slowly metabolized fructose to acetate. Provision of glutamic acid as an additional energy (ATP) source elicited rapid synthesis of polymer by glycolyzing cells. Intracellular granules were not present in glutamate-grown cells, and under anaerobic conditions, the resting cells failed to metabolize [14C] fructose. However, the addition of glutamic acid to the suspension resulted in the rapid accumulation of sugar by the cells. Approximately 15% of the 14C-labeled material was extractable with boiling water, and by 31P nuclear magnetic resonance spectroscopy, this phosphorylated derivative was identified as [14C]fructose-1-phosphate. The nonextractable material represented [14C]glucan polymer. Fructose-1-phosphate kinase activity in fructose-grown cells was fivefold greater than that in glutamate-grown cells. We suggest that the activity of fructose-1-phosphate kinase and the availability of ATP regulate the flow of fructose into either the glycolytic or polymer-synthesizing pathway in F. nucleatum. PMID- 2211507 TI - Cloning and characterization of RNA polymerase core subunits of Chlamydia trachomatis by using the polymerase chain reaction. AB - Taking advantage of sequence conservation of portions of the alpha, beta, and beta' subunits of RNA polymerase of bacteria and plant chloroplasts, we have designed degenerate oligonucleotides corresponding to these domains and used these synthetic DNA sequences as primers in a polymerase chain reaction to amplify DNA sequences from the chlamydial genome. The polymerase chain reaction products were used as a probe to recover the genomic fragments encoding the beta subunit and the 5' portion of the beta' subunit from a library of cloned murine Chlamydia trachomatis DNA. Similar attempts to recover the alpha subunit were unsuccessful. Sequence analysis demonstrated that the beta subunit of RNA polymerase was located between genes encoding the L7/L12 ribosomal protein and the beta' subunit of RNA polymerase; this organization is reminiscent of the rpoBC operon of Escherichia coli. The C. trachomatis beta subunit overproduced in E. coli was used as an antigen in rabbits to make a polyclonal antibody to this subunit. Although this polyclonal antibody specifically immunoprecipitated the beta subunit from Chlamydia-infected cells, it did not immunoprecipitate core or holoenzyme. Immunoblots with this antibody demonstrated that the beta subunit appeared early in infection. PMID- 2211508 TI - Inhibition by Agrobacterium tumefaciens and Pseudomonas savastanoi of development of the hypersensitive response elicited by Pseudomonas syringae pv. phaseolicola. AB - Injection into tobacco leaves of biotype 1 Agrobacterium tumefaciens or of Pseudomonas savastanoi inhibited the development of a visible hypersensitive response to the subsequent injection at the same site of Pseudomonas syringae pv. phaseolicola. This interference with the hypersensitive response was not seen with injection of bacterial growth medium or Escherichia coli cells. Live A. tumefaciens cells were required for the inhibitory effect. Various mutants and strains of A. tumefaciens were examined to determine the genes involved. Known chromosomal mutations generally had no effect on the ability of A. tumefaciens to inhibit the hypersensitive response, except for chvB mutants which showed a reduced (but still significant) inhibition of the hypersensitive response. Ti plasmid genes appeared to be required for the inhibition of the hypersensitive response. The bacteria did not need to be virulent in order to inhibit the hypersensitive response. Deletion of the vir region from pTi had no effect on the inhibition. However, the T region of the Ti plasmid was required for inhibition. Studies of transposon mutants suggested that the tms but not tmr or ocs genes were required. These genes were not acting after transfer to plant cells since they were effective in strains lacking vir genes and thus unable to transfer DNA to plant cells. The results suggest that the expression of the tms genes in the bacteria may inhibit the development of the hypersensitive response by the plant. An examination of the genes required in P. savastanoi for the inhibition of the hypersensitive response suggested that bacterial production of auxin was also required for the inhibition of the hypersensitive response by these bacteria. PMID- 2211509 TI - Purification and characterization of two forms of hydrogenase isoenzyme 1 from Escherichia coli. AB - A hydrogenase associated with dihydrogen uptake (HUP hydrogenase) was purified from an Escherichia coli mutant (strain SE1100) defective in utilization of molybdate and thus fermentative dihydrogen production. This protein had two subunits with apparent molecular weights of 59,000 and 28,000 (form 1). An immunologically cross-reactive hydrogenase was also purified from E. coli K10 grown in glucose-minimal medium and harvested at the mid-exponential phase of growth. Upon purification to homogeneity, this hydrogenase contained only one subunit with an apparent molecular weight of 59,000 (form 2). The two forms of the HUP hydrogenase exhibited similar kinetic characteristics. The electrophoretic properties of the enzyme and its response to pH suggest that this HUP hydrogenase is the HYD1 isoenzyme. The HYD1 isoenzyme was the only hydrogenase detectable during the stationary phase of growth in E. coli grown in Mo-deficient medium. PMID- 2211510 TI - Autoregulation of Escherichia coli purR requires two control sites downstream of the promoter. AB - The expression of Escherichia coli purR, which encodes the pur regulon repressor protein, is autoregulated. Autoregulation at the level of transcription requires two operator sites, designated purRo1 and purRo2 (O1 and O2). Operator O1 is in the region of DNA between the transcription start site and the site for translation initiation, and O2 is in the protein-coding region. The repressor protein binds noncooperatively to O1 with a sixfold-higher affinity than to O2, and saturation of O1 by the repressor precedes saturation of O2. Both O1 and O2 function in the two- to threefold autoregulation in vivo, as determined by measurement of beta-galactosidase and mRNA from purR-lacZ translational fusions. Of all the genes thus far known to be regulated by the Pur repressor, only purR employs a two-operator mechanism. PMID- 2211511 TI - Cloning, organization, and expression of the bioluminescence genes of Xenorhabdus luminescens. AB - The lux genes of Xenorhabdus luminescens, a symbiont of the nematode Heterorhabditis bacteriophora, were cloned and expressed in Escherichia coli. The expression of these genes in E. coli was qualitatively similar to their expression in X. luminescens. The organization of the genes is similar to that found in the marine luminous bacteria. Hybridization studies with the DNA that codes for the two subunits of luciferase revealed considerable homology among all of the strains of X. luminescens and with the DNA of other species of luminous bacteria, but none with the nonluminous Xenorhabdus species. Gross DNA alterations such as insertions, deletions, or inversions do not appear to be involved in the generation of dim variants known as secondary forms. PMID- 2211512 TI - In vitro replication, packaging, and transcription of the segmented double stranded RNA genome of bacteriophage phi 6: studies with procapsids assembled from plasmid-encoded proteins. AB - The genome of the lipid-containing bacteriophage phi 6 contains three segments of double-stranded RNA (dsRNA). We prepared cDNA copies of the viral genome and cloned this material in plasmids that replicate in Escherichia coli and Pseudomonas phaseolicola, the natural host of phi 6. These plasmids direct the formation of viral proteins and the assembly of structures similar to viral procapsids containing proteins P1, P2, P4, and P7. We found that these particles are capable of taking up viral single-stranded RNA and synthesizing the minus strands to produce dsRNA structures. Once the dsRNA is formed, it is then used as a template for the production of viral plus strands in a reaction that resembles normal transcription. The particles were also capable of directly transcribing exogenous dsRNA. The replicase reactions were specific for phi 6 RNA, were specific for procapsids, and resulted in substantial incorporation of product dsRNA into particles. These results offer strong support to a model in which genomic packaging is done by preformed procapsids. PMID- 2211513 TI - Cloning of genes encoding extracellular metalloproteases from Erwinia chrysanthemi EC16. AB - A 14-kilobase BamHI-EcoRI DNA fragment cloned from Erwinia chrysanthemi EC16 contained a gene encoding a metalloprotease inhibitor as well as three tandem prt genes encoding metalloproteases. The prt genes were separated from the inhibitor gene by a ca. 4-kilobase region that was necessary for extracellular secretion of the proteases. When individually subcloned downstream from vector promoters, the three prt genes each led to substantial extracellular secretion of the proteases by Escherichia coli cells, provided that the 4-kilobase required region was supplied in cis or trans. One of the protease structural genes, prtC, was sequenced and had high homology to a metalloprotease gene previously described from Serratia species as well as to the prtB gene of E. chrysanthemi B374. Marker exchange mutants of E. chrysanthemi EC16 defective in production of one or all of the extracellular proteases were not impaired in virulence on plant tissue. PMID- 2211514 TI - Association of glyoxylate and beta-oxidation enzymes with peroxisomes of Saccharomyces cerevisiae. AB - Although peroxisomes are difficult to identify in Saccharomyces cerevisiae under ordinary growth conditions, they proliferate when cells are cultured on oleic acid. We used this finding to study the protein composition of these organelles in detail. Peroxisomes from oleic acid-grown cells were purified on a discontinuous sucrose gradient; they migrated to the 46 to 50% (wt/wt) sucrose interface. The peroxisomal fraction was identified morphologically and by the presence of all of the enzymes of the peroxisomal beta-oxidation pathway. These organelles also contained a significant but minor fraction of two enzymes of the glyoxylate pathway, malate synthase and malate dehydrogenase-2. The localization of malate synthase in peroxisomes was confirmed by immunoelectron microscopy. It is postulated that glyoxylate pathway enzymes are readily and preferentially released from peroxisomes upon cell lysis, accounting for their incomplete recovery from isolated organelles. Small uninduced peroxisomes from glycerol grown cultures were detected on sucrose gradients by marker enzymes. Under these conditions, catalase, acyl-coenzyme A oxidase, and malate synthase cofractionated at equilibrium close to the mitochondrial peak, indicating smaller, less dense organelles than those from cells grown on oleic acid. Peroxisomal membranes from oleate cultures were purified by buoyant density centrifugation. Three abundant proteins of 24, 31, and 32 kilodaltons were observed. PMID- 2211515 TI - Sequence of the Klebsiella aerogenes urease genes and evidence for accessory proteins facilitating nickel incorporation. AB - A 4.8-kilobase-pair region of cloned DNA encoding the genes of the Klebsiella aerogenes urease operon has been sequenced. Six closely spaced open reading frames were found: ureA (encoding a peptide of 11.1 kilodaltons [kDa]), ureB (11.7-kDa peptide), ureC (60.3-kDa peptide), ureE (17.6-kDa peptide), ureF (25.2 kDa peptide), and ureG (21.9-kDa peptide). Immediately after the ureG gene is a putative rho-dependent transcription terminator. The three subunits of the nickel containing enzyme are encoded by ureA, ureB, and ureC based on protein structural studies and sequence homology to jack bean urease. Potential roles for ureE, ureF, and ureG were explored by deleting these accessory genes from the operon. The deletion mutant produced inactive urease, which was partially purified and found to have the same subunit stoichiometry and native size as the active enzyme but which contained no significant levels of nickel. The three accessory genes were able to activate apo-urease in vivo when they were cloned into a compatible expression vector and cotransformed into cells carrying the plasmid containing ureA, ureB, and ureC. Thus, one or more of the ureE, ureF, or ureG gene products are involved in nickel incorporation into urease. PMID- 2211516 TI - Minicell-forming mutants of Escherichia coli: suppression of both DicB- and MinD dependent division inhibition by inactivation of the minC gene product. AB - We have determined the nucleotide sequence of the minB operon of 10 min mutants of Escherichia coli, characterized by impaired inhibition of polar divisions. These mutants were either sensitive or resistant to the division inhibitor DicB. All the mutations were found to lie in minC or minD, confirming the requirement of both gene products in the process of inhibition of polar sites. Mutations conferring resistance to inhibitor DicB were found exclusively in minC. In agreement with de Boer et al. (P. A. J. de Boer, R. E. Crossley, and L. I. Rothfield, Proc. Natl. Acad. Sci. USA 87:1129-1133, 1990), these results provide evidence that, in addition to promoting division inhibition with MinD, protein MinC acts in concert with DicB to inhibit division by a second, MinD-independent process. PMID- 2211517 TI - Differential effect of mutational impairment of penicillin-binding proteins 1A and 1B on Escherichia coli strains harboring thermosensitive mutations in the cell division genes ftsA, ftsQ, ftsZ, and pbpB. AB - To study the functional differences between penicillin-binding proteins (PBPs) 1A and 1B, as well as their recently postulated involvement in the septation process (F. Garcia del Portillo, M. A. de Pedro, D. Joseleau-Petit, and R. D'Ari, J. Bacteriol. 171:4217-4221, 1989), a series of isogenic strains with mutations in the genes coding for PBP 1A (ponA) or PBP 1B (ponB) or in the cell division specific genes ftsA, ftsQ, pbpB, and ftsZ was constructed and used as the start point to produce double mutants combining the ponA or ponB characters with mutations in cell division genes. PBP 1A seemed to be unable to preserve cell integrity by itself, requiring the additional activities of PBP 2, PBP 3, and FtsQ. PBP 1B was apparently endowed with a more versatile biosynthetic potential that permitted a substantial enlargement of PBP 1A-deficient cells when PBP 2 or 3 was inhibited or when FtsQ was inactive. beta-Lactams binding to PBP 2 (mecillinam) or 3 (furazlocillin) caused rapid lysis in a ponB background. The lytic effect of furazlocillin to ponB cell division double mutants was suppressed at the restrictive temperature irrespective of the identity of the mutated cell division gene. These results indicate that PBPs 1A and 1B play distinct roles in cell wall synthesis and support the idea of a relevant involvement of PBP 1B in peptidoglycan synthesis at the time of septation. PMID- 2211518 TI - Identification and cloning of a hemin storage locus involved in the pigmentation phenotype of Yersinia pestis. AB - The temperature-dependent absorption of sufficient exogenous hemin or Congo red to form pigmented colonies of Yersinia pestis has been termed the pigmentation phenotype (Pgm+). Spontaneous mutation to a Pgm- phenotype results in the loss of a number of divergent physiological characteristics, including the ability to store hemin and to bind Congo red at 26 degrees C. In this study, we generated and isolated transposon insertion mutants that are hemin storage negative (Hms-) and therefore unable to form pigmented colonies. These mutations are due to single mini-kan insertions within a 19.5-kilobase (kb) SalI fragment of chromosomal DNA. Restriction site analysis of eight mutants identified a minimum of six potentially different insertion sites spanning an approximately 10-kb hemin storage (hms) locus. The 19.5-kb SalI fragment (containing approximately 18 kb of Y. pestis DNA and the mini-kan insert) was cloned from one of these mutants, KIM6-2012. By using this cloned fragment as a DNA probe, the mechanism of spontaneous mutation to a Pgm- phenotype was identified as a massive deletion event. The deletion spans at least 18 kb of genomic DNA in spontaneous Pgm- mutants from nine separate strains of Y. pestis. DNA adjacent to the mini-kan insert was used to identify a clone containing a wild-type hms locus. A spontaneous Pgm- mutant of Y pestis KIM containing this clone exhibits an Hms+ phenotype. The hms::mini-kan mutations and cloned wild-type hms locus generated in this study will greatly aid in identifying the function of hemin storage in Y. pestis. PMID- 2211519 TI - Development of a rickettsia isolated from an aborted bovine fetus. AB - An obligate intracellular rickettsial organism isolated from an aborted bovine fetus was studied in bovine turbinate and mouse macrophage cell cultures with light and electron microscopy. Development of the organism was similar in both cell types. The organism replicated within cytoplasmic vacuoles in a developmental cycle that resembled that of both the ehrlichiae and chlamydiae. The inoculum contained only electron-dense forms, which infected cells within 2 h postinoculation by adhering to cell membranes at thickened areas that appeared to be coated pits and then being endocytosed. A striking feature occurred next as the organisms became surrounded by host cell mitochondria and, by light microscopy, appeared to have halos. During this intimate association with mitochondria, the electron-dense organisms changed into large reticulated forms that began to divide by binary fission. These large forms were often in direct contact with mitochondrial membranes. The organisms continued to divide by binary fission, and host cells contained large cytoplasmic inclusions of reticulated organisms. The reticulated organisms gradually changed into electron-dense forms that were released from degenerated host cells. PMID- 2211520 TI - Nucleotide sequence of a Pseudomonas denitrificans 5.4-kilobase DNA fragment containing five cob genes and identification of structural genes encoding S adenosyl-L-methionine: uroporphyrinogen III methyltransferase and cobyrinic acid a,c-diamide synthase. AB - A 5.4-kilobase DNA fragment carrying Pseudomonas denitrificans cob genes has been sequenced. The nucleotide sequence and genetic analysis revealed that this fragment carries five different cob genes (cobA to cobE). Four of these genes present the characteristics of translationally coupled genes. cobA has been identified as the structural gene of S-adenosyl-L-methionine:uroporphyrinogen III methyltransferase (SUMT) because the encoded protein has the same NH2 terminus and molecular weight as those determined for the purified SUMT. For the same reasons the cobB gene was shown to be the structural gene for cobyrinic acid a,c diamide synthase. Genetic and biochemical data concerning cobC and cobD mutants suggest that the products of these genes are involved in the conversion of cobyric acid to cobinamide. PMID- 2211521 TI - Genetic and sequence analysis of an 8.7-kilobase Pseudomonas denitrificans fragment carrying eight genes involved in transformation of precorrin-2 to cobyrinic acid. AB - A 8.7-kilobase DNA fragment carrying Pseudomonas denitrificans cob genes has been sequenced. The nucleotide sequence and the genetic analysis revealed that this fragment carries eight different cob genes (cobF to cobM). Six of these genes have the characteristics of translationally coupled genes. cobI has been identified as S-adenosyl-L-methionine (SAM):precorrin-2 methyltransferase structural gene because the encoded protein has the same NH2 terminus and molecular weight as those of the purified enzyme. From protein homology with CobA and CobI, two SAM-dependent methyltransferases of the cobalamin pathway, it is proposed that cobF, cobJ, cobL, and cobM code for other methyltransferases involved in the cobalamin pathway. In addition, purified CobF protein has affinity for SAM, as expected for a SAM-dependent methyltransferase. Accumulation of cobalamin precursors in Agrobacterium tumefaciens mutants complemented by any of these eight genes suggest that, apart from cobI, whose function is identified, the products of all these genes are implicated in the conversion of precorrin-3 into cobyrinic acid. PMID- 2211522 TI - The ClpP component of Clp protease is the sigma 32-dependent heat shock protein F21.5. AB - The genes that encode the subunits of the Clp protease of Escherichia coli, clpA and clpP, appear to be regulated differently from each other. The clpA gene does not seem to be under heat shock control (Y. S. Katayama, S. Gottesman, J. Pumphrey, S. Rudikoff, W. P. Clark, and M. R. Maurizi, J. Biol. Chem. 263:15226 15236, 1988). In contrast, the level of ClpP protein was increased in rpoH+ cells but not in null rpoH cells after an upshift in temperature from 17 to 43 degrees C. The level of ClpP protein in a null dnaK strain was also elevated relative to the level of ClpP protein in an otherwise isogenic dnaK+ strain. In two dimensional gels, the ClpP protein was located in the position of the previously unidentified heat shock protein F21.5. No protein spot corresponding to F21.5 was present in two-dimensional gels of a null clpP strain. The clpP gene, therefore, appears to be a heat shock gene, expressed in a sigma 32-dependent manner and negatively regulated by DnaK; the product of clpP is the previously unidentified heat shock protein F21.5. PMID- 2211523 TI - Mutational analysis of the VirG protein, a transcriptional activator of Agrobacterium tumefaciens virulence genes. AB - The VirG protein of Agrobacterium tumefaciens is required in conjunction with the VirA protein for transcriptional activation of the virulence (vir) genes in response to plant phenolic compounds. These proteins are members of a family of two component regulatory systems. vir genes are activated via a cascade of phosphorylation reactions involving a specific aspartic acid residue of the VirG protein. We have conducted a mutational analysis of the VirG protein. By mutating conserved and nonconserved aspartic acid residues in the N-terminal domain, we demonstrated that two of three conserved aspartic acid residues located in two different regions are important for the phosphorylation of VirG by VirA phosphate. A third conserved N-terminal region was also shown to be critical for the biological function of VirG as a transcriptional activator. The identification of phosphorylatable but biologically inactive mutated VirG proteins suggests that not only phosphorylation but also a conformational change is necessary for its activity. We further demonstrated that phosphorylation is not required for sequence-specific binding to a vir gene regulatory sequence (vir box) and that the C-terminal domain is sufficient for DNA binding. The data support the model of a two-domain structure for the VirG protein and demonstrate that the sequence homologies to other two-component regulatory systems reflect both functional and structural homologies. PMID- 2211524 TI - Identification of a Caulobacter basal body structural gene and a cis-acting site required for activation of transcription. AB - The genes that encode the components and regulatory proteins of the Caulobacter crescentus flagellum are transcribed at specific times in the cell cycle. One of these genes, flbN, is required early in the flagellar assembly process. The flbN gene was cloned and sequenced, and the time of transcription activation was determined. The derived amino acid sequence indicates that fibN encodes a 25 kilodalton protein with a cleavable leader peptide. The flbN-encoded protein has 30.8% identity with the protein encoded by the Salmonella typhimurium basal body L-ring gene, flgH. Site-directed mutagenesis and gel mobility shift assays identified a binding site at -100 from the transcription start site for a trans acting protein, RF-2, that functions to partially activate flbN transcription at a defined time in the cell cycle. The RF-2 binding region is similar to a NifA binding site normally used in the activation of some sigma 54 promoters involved in nitrogen fixation in other bacteria. Transcription of a flbN-reporter gene fusion in an Escherichia coli background was dependent on the presence of a NifA transcription factor supplied by a plasmid-borne Rhizobium meliloti gene encoding NifA. A deletion or base changes in the RF-2 binding region eliminated expression of the flbN gene in E. coli even when a NifA protein was provided in trans, suggesting that a sigma 54 promoter with an upstream activator element is used by the C. crescentus flbN gene. A consensus sequence for a sigma 54 promoter was found at the appropriate distance 5' to one of two identified transcription start sites. Site-directed mutagenesis confirmed that a conserved nucleotide in this sigma 54 promoter consensus sequence was required for transcription. Deletion of the region 5' to the apparent sigma 54 promoter caused a complete loss of transcription activation. Transcription activation of flbN in C. crescentus involves the combination of several elements: the NifA-like site is required for full activation, and other sequence elements 5' to the promoter and 3' to the transcription start site are necessary for the correct time of transcription initiation. PMID- 2211525 TI - Evidence that there are only two tRNA(Phe) genes in Escherichia coli. AB - pheV, one of the genes that code for tRNA(Phe), was deleted from the chromosome of a strain of Escherichia coli K-12. As a consequence of this mutation, expression of pheA, the gene for chorismate mutase P-prephenate dehydratase, the first enzyme in the terminal pathway of phenylalanine biosynthesis, was derepressed. Similar derepression of pheA has been reported in pheR mutants of E. coli K-12 (J. Gowrishankar and J. Pittard, J. Bacteriol. 150:1130-1137, 1982). Attempts to introduce a pheR mutation into the delta pheV strain failed under circumstances suggesting that this combination of mutations is lethal. Southern blot analysis of pheV+ and delta pheV strains indicated that there are only two tRNA(Phe) genes in E. coli. It is recommended that the names pheU and pheV be retained for these genes. PMID- 2211526 TI - Synthesis of the iron-molybdenum cofactor of nitrogenase is inhibited by a low molecular-weight metabolite of Klebsiella pneumoniae. AB - The in vitro synthesis of the iron-molybdenum cofactor nitrogenase was inhibited by a low-molecular-weight factor. This inhibitory factor was present in the membrane extracts of wild-type and nif mutant strains of Klebsiella pneumoniae that were grown under conditions that either repressed or derepressed nitrogenase expression. In vitro, the inhibition was specific for the NifB protein. Addition of this factor to K. pneumoniae cells at various times during nif derepression decreased nitrogenase activity, presumably through inhibition of iron-molybdenum cofactor synthesis. The inhibitor was purified by solvent extraction and chromatography on DEAE-cellulose, silica gel, and aluminum oxide columns. PMID- 2211527 TI - Spiralins of Spiroplasma citri and Spiroplasma melliferum: amino acid sequences and putative organization in the cell membrane. AB - Spiralin is the major membrane protein of the helical mollicute Spiroplasma citri. A similar protein occurs in the membrane of Spiroplasma melliferum, an organism related to S. citri. The gene encoding spiralin has been sequenced. A restriction fragment of the spiralin gene has been used as a probe to detect the gene encoding S. melliferum spiralin. A 4.6-kilobase-pair ClaI DNA fragment from S. melliferum strongly hybridized with the probe. This fragment was inserted in pBR322 and cloned in Escherichia coli. It was further subcloned in the replicative forms of M13mp18 and M13mp19, and its nucleotide sequence was determined (GenBank accession number M33991). An open reading frame showing 88.6% base sequence homology with the S. citri spiralin gene could be identified and was assumed to be the gene encoding S. melliferum spiralin. The deduced amino acid sequence of the protein had 75% homology with the spiralin sequence. In particular, the two proteins possess a stretch of 20 amino acids which can form an alpha-helix, in which all polar amino acids occupy approximately one-third of the axial projection down the helix. On the basis of these data and published data, we propose a topological model for the structural organization of the spiralin in the cell membrane of spiroplasmas. PMID- 2211528 TI - Relationship of cellulosomal and noncellulosomal xylanases of Clostridium thermocellum to cellulose-degrading enzymes. AB - Xylanase activity of Clostridium thermocellum, an anaerobic thermophilic cellulolytic bacterium, was characterized. The activity was localized both in the cellulosome (the principal multienzyme, cellulose-solubilizing protein complex) and in noncellulosomal fractions. Each of these fractions contained at least four major polypeptide bands which contributed to the xylanolytic activity. In both cases, pH and temperature optima, product pattern, and other features of the xylanase activity were almost identical. The main difference was in the average molecular weights of the respective polypeptides which appeared responsible for the activity. In the noncellulosomal fraction, xylanases with Mrs ranging from 30,000 to 65,000 were detected. Distinct from these were the cellulosomal xylanases, which exhibited much larger Mrs (up to 170,000). The cellulosome associated xylanases corresponded to known cellulosomal subunits, some of which also exhibited endoglucanase activity, and others which coincided with subunits which appeared to express exoglucanaselike activity. In contrast, the noncellulosomal xylanases hydrolyzed xylan exclusively. beta-Glucosidase and beta xylosidase activities were shown to be the action of different enzymes; both were associated exclusively with the cell and were not components of the cellulosome. Despite the lack of growth on and utilization of xylan or its degradation products, C. thermocellum produces a highly developed xylanolytic apparatus which is interlinked with its cellulase system. PMID- 2211529 TI - groE genes affect SOS repair in Escherichia coli. AB - Repair of UV-irradiated bacteriophage in Escherichia coli by Weigle reactivation requires functional recA+ and umuD+C+ genes. When the cells were UV irradiated, the groE heat shock gene products, GroES and GroEL, were needed for at least 50% of the Weigle reactivation of the single-stranded DNA phage S13. Because of repression of the umuDC and recA genes, Weigle reactivation is normally blocked by the lexA3(Ind-) mutation (which creates a noncleavable LexA protein), but it was restored by a combination of a high-copy-number umuD+C+ plasmid and a UV dose that increases groE expression. Maximal reactivation was achieved by elevated amounts of the Umu proteins, which was accomplished in part by UV-induced expression of the groE genes. By increasing the number of copies of the umuD+C+ genes, up to 50% of the normal amount of reactivation of S13 was achieved in an unirradiated recA+ host. PMID- 2211530 TI - Penicillin-binding proteins in Borrelia burgdorferi. AB - Penicillin-binding proteins were identified in Borrelia burgdorferi membranes. A 94-kilodalton penicillin-binding protein was the first to be labeled with tritiated penicillin and was the first band to disappear in a competition experiment. Its binding ability was destroyed when membranes were preboiled. In addition, several of these penicillin-binding proteins comigrated with bands previously identified as surface proteins. PMID- 2211531 TI - The lpd gene product functions as the L protein in the Escherichia coli glycine cleavage enzyme system. AB - The lpd-encoded lipoamide dehydrogenase, common to the pyruvate and 2 oxoglutarate dehydrogenase multienzyme complexes, also functions as the lipoamide dehydrogenase (L protein) in the Escherichia coli glycine cleavage (GCV) enzyme complex. Inducible GCV enzyme activity was not detected in an lpd deletion mutant; lpd+ transductants had normal levels of inducible GCV enzyme activity. A serA lpd double mutant was unable to utilize glycine as a serine source and lacked detectable GCV enzyme activity, the phenotype of a serA gcv mutant. Transformation of the double mutant with a plasmid encoding a functional lpd gene restored the ability of the mutant to use glycine as a serine source and restored inducible GCV enzyme activity to normal levels. The presence of acetate and succinate in the growth medium of a strain wild type for lpd and gcv resulted in a 50% reduction in inducible GCV enzyme activity. Enzyme levels were restored to normal under these growth conditions when the strain was transformed with a plasmid encoding a functional lpd gene. PMID- 2211532 TI - Molecular cloning, nucleotide sequence, and promoter structure of the Acinetobacter calcoaceticus trpFB operon. AB - The trpFB operon from Acinetobacter calcoaceticus encoding the phosphoribosyl anthranilate isomerase and the beta-subunit of tryptophan synthase has been cloned by complementation of a trpB mutation in A. calcoaceticus, identified by deletion analysis, and sequenced. It encodes potential polypeptides of 214 amino acids with a calculated molecular weight of 23,008 (TrpF) and 403 amino acids with a molecular weight of 44,296 (TrpB). The encoded TrpB sequence shows striking homologies to those from other bacteria, ranging from 47% amino acids identity with the Brevibacterium lactofermentum protein and 64% identity with the Caulobacter crescentus protein. The encoded TrpF sequence, on the other hand, is much less homologous to the ones from other species, ranging between 27% identity with the Bacillus subtilis enzyme and 36% identity with the C. crescentus enzyme. The homologies of both polypeptides are evenly distributed over the entire sequences. The codon usage shows the strong preference for A and T in the third positions typical for A. calcoaceticus genes. The trpFB operon appears to be unlinked to trpA. The trpFB promoter has been determined by primer extension analysis of RNA synthesized from the chromosomally and plasmid-encoded trpFB operons. The starting nucleotides are identical in both cases and define the first promoter from A. calcoaceticus. Potential regulatory features are implied by a palindromic element overlapping the -35 consensus box of the promoter. PMID- 2211533 TI - Presence of N6-methyladenine in GATC sequences of Bacillus popilliae and Bacillus lentimorbus KLN2. AB - Nine strains of Bacillus popilliae and Bacillus lentimorbus KLN2 contain N6 methyladenine in GATC sequences, as determined by using the restriction enzymes MboI and DpnI. Among eight other Bacillus species examined, all, except one strain of Bacillus brevis (ATCC 9999), lacked adenine methylation in GATC. A methylase with Escherichia coli dcm site specificity was not present in any of the Bacillus species studied. PMID- 2211534 TI - Selection of Acinetobacter calcoaceticus mutants deficient in the p hydroxybenzoate hydroxylase gene (pobA), a member of a supraoperonic cluster. AB - p-Hydroxybenzoate hydroxylase, the product of the pobA gene, gives rise to protocatechuate, which is metabolized by enzymes encoded by the pca operon in Acinetobacter calcoaceticus. Mutations in pcaD prevented growth of A. calcoaceticus with succinate in the presence of p-hydroxybenzoate. Mutants selected on this medium contained the original mutation in pcaD and also carried spontaneous mutations in pobA. These independently expressed genes were cotransformed with a frequency of 15% and thus are components of a supraoperonic cluster. PMID- 2211535 TI - Nucleotide sequence analysis of the Leptospira biflexa serovar patoc rpsL and rpsG genes. AB - The Leptospira biflexa rpsL and rpsG genes were sequenced. Although similar in many respects, proteins encoded by these L. biflexa genes had several unusual features when compared with homologous proteins of other organisms. Unlike the rpsL genes of other eubacteria, the L. biflexa rpsL gene is adjacent to a rpoC like gene. PMID- 2211536 TI - Recovery of DNA from the Acinetobacter calcoaceticus chromosome by gap repair. AB - A strain of Acinetobacter calcoaceticus that demonstrates unusually high competence for natural transformation by linear DNA has proven valuable for analysis of genes and gene clusters associated with aromatic catabolism. The transformation system allowed gap repair to be used to recover mutant chromosomal DNA within recombinant plasmids. The sizes of the recovered fragments, 5 and 7 kilobase pairs in length, indicate that gap repair will be a useful procedure for isolation of wild-type and modified gene clusters from the A. calcoaceticus chromosome. PMID- 2211537 TI - Bipolar disorder and Crohn's disease. AB - Despite an extensive literature examining the relationship between Crohn's disease and psychiatric illness, there is only one published report of mania in a patient with Crohn's disease. The authors describe seven patients, six men and one woman, with both bipolar disorder and Crohn's disease. The age at onset of Crohn's disease was highly correlated with the age at onset of affective disorder (r = .89, p = .016) and mania (r = .79, p = .06). Four patients received prednisone therapy for Crohn's disease from 3 to 52 weeks before their first manic episode. The authors discuss the relationship of the two illnesses, including possible common provoking factors, the possible role of steroids, and the genetics of the disorders. PMID- 2211538 TI - Lithium treatment during pregnancy, delivery, and lactation: an update. AB - Because prophylactic lithium treatment is often given to manic depressive women of fertile age, the answers to five questions are pressing: (1) Does lithium administration during pregnancy expose the unborn child to risk of malformations? (2) Does such exposure lead to later developmental anomalies? (3) Do changes in the pharmacokinetics of lithium during pregnancy and delivery require special precautions? (4) Does lithium treatment during pregnancy exert other effects? (5) Is it advisable that women in lithium treatment breastfeed their infants? The author discusses these questions in the light of present-day knowledge and proposes guidelines for lithium treatment during pregnancy, delivery, and lactation. PMID- 2211539 TI - Blood pressure reduction with ECT response. AB - A group of 48 male inpatients who responded to electroconvulsive therapy for major depression showed decreases in resting blood pressure along the course of treatment. Decreases occurred in both systolic (mean +/- SD = 8.0 +/- 17.3 mm Hg, p = .0025) and diastolic (7.4 +/- 13.2 mm Hg, p = .00030) pressures. Systolic pressure decreased by at least 20 mm Hg in 15 patients. These findings are consistent with reports that depressives show elevated plasma catecholamine levels, and that, with response to tricyclic antidepressants, their blood pressures decrease. Depression-associated blood pressure elevation might contribute to the excessive cardiac mortality of depressives; conversely, antidepressant treatment might control hypertension in some depressives. PMID- 2211540 TI - Hoarding as a psychiatric symptom. AB - Collecting is a normal behavior in childhood and adulthood, while hoarding--the gathering, ordering, and disposal of articles without clear conscious motivation or control--is characterized as the pathologic counterpart of collecting. The literature describing the characteristics of collecting and the theories concerning its underlying mechanisms is presented along with eight case studies of adults who exhibited hoarding as a prominent symptom. It is apparent that hoarding is the final common pathway for a variety of processes: compulsive hoarding in obsessive compulsive disorder, fears of theft and poisoning in paranoid delusions, and the deterioration of habits in organic mental disorder. PMID- 2211541 TI - Tranylcypromine addiction: a case report and review. AB - The authors report a case of tranylcypromine addiction and review the literature on the subject. Since the drug was first marketed in 1960, a total of 18 cases have been described. Predisposing risk factors and potential mechanisms for addiction are discussed. Given the current trend toward using tranylcypromine more frequently and in higher therapeutic doses for refractory depression, a greater index of suspicion for self-medication with this drug is warranted. PMID- 2211542 TI - Psychotropic medication and priapism: a comprehensive review. AB - Numerous reports have emphasized the association between priapism and the ingestion of psychotropic medication. Clinicians are becoming increasingly aware of this association and its subsequent severe morbidity. Review of the literature reveals that medications possessing alpha-adrenergic blocking properties are most frequently associated with priapism. These medications include trazodone, several antipsychotics, and the antihypertensive agent, prazosin. Awareness of these associations and an appreciation of potentially serious consequences of this disorder may assist clinicians in choosing psychotropic agents that minimize the risk of developing priapism. It is essential that patients who are to receive psychotropic medications be forewarned about priapism. In addition, patients should be questioned concerning prior occurrence of prolonged erections, since a past history of delayed detumescence is present in approximately 50% of subsequent cases of priapism. PMID- 2211543 TI - A case of autoimmune thyroiditis presenting as menstrual related mood disorder. AB - A case of autoimmune thyroiditis presenting as menstrual related mood disorder (MRMD) is described. The symptoms of the patient's prospectively confirmed MRMD remitted following thyroid hormone supplementation. Although most patients with prospectively confirmed MRMD are not clinically hypothyroid or hyperthyroid, the importance of routine thyroid function tests in the initial evaluation of MRMD is underscored by the successful treatment of this patient with thyroid hormone replacement. PMID- 2211544 TI - Serotonergic activity and hostility. PMID- 2211545 TI - Complex partial seizure symptoms affected by marijuana abuse. PMID- 2211546 TI - Panic disorder and cocaine abuse in alcoholics. PMID- 2211547 TI - Catatonic syndrome in a general psychiatric inpatient population: frequency, clinical presentation, and response to lorazepam. AB - In a prospective open trial conducted on a general psychiatric ward, the authors diagnosed catatonic syndrome 15 times in 12 patients over a 1-year period. These 12 patients represented 9% of all admissions. The following signs were present in two thirds or more of the episodes studied: immobility (100%), staring (92%), mutism (85%), withdrawal/refusal to eat (78%), posturing/grimacing (73%), and rigidity (66%). Other signs of catatonia were seen less frequently. Lorazepam 1 to 2 mg was administered in every case, and patients were evaluated at hourly intervals. Of the 15 episodes, 12 responded completely and dramatically to lorazepam treatment within 2 hours, 1 responded partially, and 2 had no response. Adverse effects were infrequent. A CNS abnormality or dysfunction was evident in 8 of the 12 responders, suggesting that a beneficial response to lorazepam is not limited to patients with pure psychogenic catatonia. The prompt recognition and treatment of catatonia may reduce morbidity in and length of stay for hospitalized psychiatric patients. PMID- 2211548 TI - Usefulness of screening EEGs in a psychiatric inpatient population. AB - Many clinicians presume that a screening electroencephalogram (EEG) is useful in differentiating psychiatric from neurologic disorders. In a retrospective review of 698 charts of psychiatric inpatients, the authors assessed the usefulness of screening EEGs. Usefulness was defined as leading to a change in diagnosis or treatment. While 31% of screening EEGs were abnormal, only 1.7% of cases led to a change in diagnosis that might otherwise have been missed. It is unclear whether the EEG is a useful screening test on the basis of these results. Caution is warranted in interpreting these results because of the inaccuracies inherent in any retrospective review. Prospective studies are needed to better define EEG's usefulness in psychiatry. PMID- 2211549 TI - Postpartum psychosis with abnormal movements: dopamine supersensitivity unmasked by withdrawal of endogenous estrogens? AB - The authors describe two cases of postpartum psychosis accompanied by abnormal extrapyramidal movements. The presentation of these cases, as well as research evidence indicating that estrogens influence dopamine receptor function, leads the authors to hypothesize that dopamine receptor supersensitivity may have been induced by prepartum increases in endogenous estrogens and unmasked by postpartum estrogen withdrawal. PMID- 2211550 TI - Reversal of fluoxetine-induced anorgasmia by cyproheptadine in two patients. AB - The authors report two cases of ejaculatory dysfunction induced by fluoxetine. Cyproheptadine, an antihistaminic and antiserotonergic drug, restored sexual function in each case. Possible mechanisms of fluoxetine-induced anorgasmia are presented and treatment options are reviewed. PMID- 2211551 TI - Phenelzine treatment of elective mutism: a case report. AB - A 7-year-old girl with a 2-year history of elective mutism was successfully treated with phenelzine. The only side effects of treatment were mild constipation and weight gain. Talkativeness as a dopaminergic behavioral effect of phenelzine is described. On the basis of the case report and the literature, the authors raise nosologic questions concerning elective mutism and social phobia. PMID- 2211552 TI - Fluoxetine-induced bradycardia and syncope in two patients. AB - Fluoxetine appears to cause a low incidence of adverse cardiac effects. An uncommon but potentially hazardous effect of fluoxetine therapy, however, is bradycardia accompanied by faintness or syncope. The authors report two cases in which this adverse effect occurred. They hypothesize that the mechanism of bradycardia in these cases represents a direct central nervous system effect of increased serotonin on medullary cardiovascular regulation. PMID- 2211553 TI - Depression and organic mood disorder. PMID- 2211554 TI - Isoniazid-induced obsessive compulsive neurosis. PMID- 2211555 TI - Edgar Allan Poe's "William Wilson" and Capgras syndrome. PMID- 2211556 TI - Schizophrenic individuals with bipolar first-degree relatives. PMID- 2211557 TI - Current and potential uses of lithium. PMID- 2211558 TI - Innovative treatment strategies: practical management of anxiety and related disorders. A symposium held in conjunction with the 143rd annual meeting of the American Psychiatric Association. May 1990, New York, New York. Proceedings. PMID- 2211559 TI - Sleep laboratory evaluation of the effects and efficacy of trazodone in depressed insomniac patients. AB - Trazodone (150 mg to 400 mg) was administered to six depressed patients with significant sleep disturbances in an 8-week single-blind study design. Patients were evaluated psychologically by means of the Hamilton Rating Scales for Anxiety and Depression. Polysomnographic monitoring in the sleep laboratory was conducted at each of the time points corresponding to the psychiatric evaluations. Five of the six subjects completed treatment. Patients showed a significant improvement in symptoms of depression and in their polysomnographic-determined sleep architecture. There was a 44% improvement in persistent sleep latency, decreasing from a mean +/- SD of 51.0 +/- 59.3 minutes at baseline to 28.5 +/- 24.2 minutes after 5 weeks of active treatment. Total sleep time improved 14% from 387.1 +/- 59.2 minutes at baseline to 441.3 +/- 23.7 minutes after 5 weeks. Stage IV sleep more than doubled with an increase of 153% from 1.9 +/- 3.0% at baseline to a more normal 4.8 +/- 5.5%. There was no change in percentage of rapid eye movement (REM); however, REM latency increased 28% from a mean of 74.6 +/- 35.9 minutes at baseline to a mean of 95.6 +/- 28.8 minutes. Sleep efficiency improved from 80.6 +/- 12.3%, considered clinically significant insomnia, to 91.9 +/- 4.9%, which is well within normal sleep patterns. PMID- 2211560 TI - Increased deep sleep after trazodone use: a double-blind placebo-controlled study in healthy young adults. AB - The effects of trazodone on sleep were compared with those of placebo and the sedating tricyclic antidepressant trimipramine in a double-blind crossover study in six healthy young men. Only trazodone significantly increased deep sleep without otherwise altering the normal architecture of sleep. The alpha-adrenergic receptor-blocking property of trazodone and a relative lack of noradrenergic reuptake blocking and the lack of anticholinergic effects are hypothesized to be responsible for the effects on sleep. PMID- 2211561 TI - Trazodone dosing regimen: experience with single daily administration. AB - Efficacy being constant, antidepressant choice is dictated by side effect profile, patient acceptance, and safety. Trazodone has been shown to be safe in overdose, and the side effect profile is mild, with sedation the most common side effect. Sleep electroencephalogram and clinical studies have shown trazodone effective in improving sleep in normal subjects, insomniac patients, and patients with major depression. Tolerance and rapid eye movement rebound on discontinuation do not occur. The 3- to 9-hour half-life of trazodone and its pharmacokinetics favors a dose weighted at bedtime. Studies comparing multiple daytime dosing to single dosing at bedtime have shown equal efficacy in relieving depression. At treatment onset, a single nighttime dose is more productive of sleep with less daytime drowsiness. These differences between single nighttime dosing and multiple daily dosing disappear with continued administration. Geriatric patients respond similarly. Trazodone is best dosed at 150 mg given predominantly (but not necessarily all) at bedtime and increased as needed to 200 to 300 mg for full antidepressant efficacy. PMID- 2211563 TI - Serotonin partial agonists in the treatment of anxiety and depression. Introduction. PMID- 2211562 TI - A drug utilization review of prescribing patterns for trazodone versus amitriptyline. AB - The second-generation antidepressant trazodone has been thought by some clinicians to exert a less robust antidepressant effect than do tricyclic agents. This impression differs from the findings of numerous published clinical trials. In an effort to determine whether this discrepancy may be due to possible inappropriate dosing or use of trazodone for different patient subtypes, a retrospective chart review of 138 depressed inpatients treated with amitriptyline and of 42 depressed inpatients treated with trazodone was performed to compare their respective prescribing patterns. While these two groups did not differ with regard to most demographic variables, results revealed that patient prescribed trazodone were older (trazodone, mean +/- SD age = 54.5 +/- 8.8 years versus amitriptyline, 43.2 +/- 12.9 years; p less than .001), more often had a recurrent depressive disorder (trazodone = 57.1%, amitriptyline = 39.1%, p less than .06), and more frequently had a history of unresponsiveness to other antidepressants (trazodone = 47.6%, amitriptyline = 11.6%; p less than .001). In addition, initially prescribed daily doses of trazodone were below the recommended starting dose of 150 mg/day (mean +/- SD starting dose = 113.7 +/- 42.1 mg/day), while starting daily doses for amitriptyline (mean +/- SD = 69.8 +/- 20.1 mg/day) were judged to be more adequate relative to the recommended daily dose of 75 mg/day. Final trazodone dosage (mean +/- SD final dose = 217.9 +/- 87.5 mg/day) could be judged to have been far short of optimal levels of 250 to 350 mg/day and of up to 600 mg/day for inpatients and 400 mg/day for outpatient.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2211564 TI - Treatment of generalized anxiety disorder: preliminary clinical experience with buspirone. AB - The authors reviewed pharmacologic treatment of generalized anxiety disorder (GAD), particularly treatment with benzodiazepine agents, and compared the antianxiety effects and dependence risks of these agents with those of nonGABAergic compounds such as buspirone--a new psychotropic drug--in the treatment of chronic anxiety. Forty outpatients who met DSM-III criteria for GAD were randomly assigned to double-blind treatment with buspirone or lorazepam. After 8 weeks, treatment was abruptly stopped and withdrawal reactions were evaluated at Weeks 9 and 10. After 3 to 4 weeks, buspirone's efficacy in treating GAD symptomatology was found to be comparable with lorazepam's, except for sleep disturbances, which were minimally affected by buspirone. After treatment was discontinued, buspirone-treated patients were free from withdrawal symptoms, while the symptoms of lorazepam-treated patients worsened at Week 9. PMID- 2211565 TI - New uses of hypnosis in the treatment of posttraumatic stress disorder. AB - Hypnosis is associated with the treatment of posttraumatic stress disorder (PTSD) for two reasons: (1) the similarity between hypnotic phenomena and the symptoms of PTSD, and (2) the utility of hypnosis as a tool in treatment. Physical trauma produces a sudden discontinuity in cognitive and emotional experience that often persists after the trauma is over. This results in symptoms such as psychogenic amnesia, intrusive reliving of the event as if it were recurring, numbing of responsiveness, and hypersensitivity to stimuli. Two studies have shown that Vietnam veterans with PTSD have higher than normal hypnotizability scores on standardized tests. Likewise, a history of physical abuse in childhood has been shown to be strongly associated with dissociative symptoms later in life. Furthermore, dissociative symptoms during and soon after traumatic experience predict later PTSD. Formal hypnotic procedures are especially helpful because this population is highly hypnotizable. Hypnosis provides controlled access to memories that may otherwise be kept out of consciousness. New uses of hypnosis in the psychotherapy of PTSD victims involve coupling access to the dissociated traumatic memories with positive restructuring of those memories. Hypnosis can be used to help patients face and bear a traumatic experience by embedding it in a new context, acknowledging helplessness during the event, and yet linking that experience with remoralizing memories such as efforts at self-protection, shared affection with friends who were killed, or the ability to control the environment at other times. In this way, hypnosis can be used to provide controlled access to memories that are then placed into a broader perspective. Patients can be taught self-hypnosis techniques that allow them to work through traumatic memories and thereby reduce spontaneous unbidden intrusive recollections. PMID- 2211566 TI - Insights in the use of trazodone in depressed patients. PMID- 2211568 TI - Concurrent use of buspirone in anxious patients during withdrawal from alprazolam therapy. AB - A multicenter, double-blind, placebo-controlled study was conducted to determine the safety of concurrently using buspirone with alprazolam before and during a gradual tapering of the alprazolam dose. Thirty-six patients received placebo t.i.d. and 36 received buspirone 5 mg. t.i.d. Findings included significantly greater anxiety (as measured by the Hamilton Rating Scale for Anxiety) in the placebo group and significantly reduced manifestations of abstinence (as measured by the Abstinence Rating Scale) in the buspirone group. Buspirone and alprazolam may be used together safely, and buspirone may be started early in the alprazolam tapering process. PMID- 2211567 TI - A double-blind, controlled trial in primary care patients with generalized anxiety: a comparison between buspirone and oxazepam. AB - Two hundred thirty patients with generalized anxiety and Hamilton Rating Scale for Anxiety (HAM-A) scores greater than or equal to 18 were subdivided at random, according to a double-blind design, into one group treated with 5-10 mg of oral buspirone t.i.d. or one group treated with 10-20 mg of oral oxazepam t.i.d. for 6 weeks. No anxiolytic treatment was allowed 3 months prior to trial entry. Analysis of demographic variables revealed no significant imbalance between the two treatment groups. Twenty patients were excluded from efficacy analysis because of treatment withdrawal before the first efficacy evaluation on Day 7. Another 4 patients were excluded because they were taking concomitant psychotropic medication. The remaining 206 patients displayed a decrease in HAM-A scores (mean +/- SD) from 23.9 +/- 4.1 to 10.6 +/- 7.7 in the buspirone group and from 23.9 +/- 4.2 to 11.5 +/- 8.0 in the oxazepam group. The two treatment groups were also found to be virtually identical in an "intent to treat" analysis of all 230 patients as well as in other ratings (Hamilton Rating Scale for Depression, Raskin Depression Scale, Covi Anxiety Scale, Physicians Questionnaire, global ratings, and Hopkins Symptom Checklist [HSCL]-56). However, oxazepam was never superior to buspirone in any of the efficacy analyses. Of the 230 patients, 127 spontaneously reported adverse events, including drowsiness, dizziness, headache, nausea, and nervousness. Adverse events were relatively similar in the two groups. In conclusion, buspirone and oxazepam appear to be equally effective in the treatment of generalized anxiety encountered by general practitioners. This outcome, in addition to a previously documented absence of any dependency liability, makes buspirone a clinically important anxiolytic drug. PMID- 2211569 TI - Buspirone in clinical practice. AB - Buspirone, an azapirone derivative and a 5-HT1A partial agonist, is the first nonbenzodiazepine anxiolytic introduced into medicine for the treatment of generalized anxiety disorder. A series of well-controlled clinical trials demonstrated that its anxiolytic properties were similar to those of various benzodiazepines and significantly better than placebo. More recently, antidepressant effects were also observed. Patients with clinical indications for which buspirone seems to be particularly appropriate are those with generalized anxiety disorder, those with chronic anxiety, the anxious elderly, and, perhaps, many patients of all ages who suffer from mixed symptoms of anxiety and depression. Studies conducted with patients suffering from panic disorder have so far been inconclusive, and thus buspirone is, for the present at least, not recommended for routine treatment of panic disorder. Buspirone seems to be most helpful in anxious patients who do not demand immediate gratification or the immediate relief they associate with the benzodiazepine response. Slower and more gradual onset of anxiety relief is balanced by the increased safety and lack of dependency-producing aspects of buspirone. Finally, whether or not buspirone may possess "curative" properties, in addition to "anxiety-suppressant" properties, that allow the patient to improve coping skills with time requires further exploration. PMID- 2211570 TI - Buspirone in the management of major depression: a placebo-controlled comparison. AB - One hundred forty outpatients with major depression were admitted to an 8-week, placebo-controlled, double-blind study of buspirone. Entry criteria included a Hamilton Rating Scale for Depression (25-item [HAM-D]) score of greater than or equal to 18 and a Hamilton Rating Scale for Anxiety (HAM-A), score of greater than or equal to 18. A flexible dose schedule ranging from 5-90 mg/day was employed. The mean dose of buspirone was 41-54 mg/day from Week 2 to the end of the study. Sixty-four percent of buspirone patients and 50% of placebo patients were melancholic; 64% of buspirone patients and 74% of placebo patients discontinued treatment before the end of the study. Extender data analysis showed that buspirone patients had significant (p less than .05) HAM-D score reductions compared with the placebo group at Weeks 2, 3, 4, and 6. The HAM-D retardation factor trended toward significance over placebo at Weeks 3, 4, and 6. HAM-D change scores for the subgroup of melancholic patients taking buspirone were significantly (p less than .02) better than those of the placebo-treated melancholic subjects at Weeks 2, 3, 4, and 6. Most other efficacy parameters also favored the buspirone-treated group over the placebo-treated group. The most common adverse experiences for the buspirone group were CNS effects (74% in the buspirone group vs. 21% in the placebo group) and gastrointestinal effects (55% in the buspirone group vs. 37% in the placebo group). Side effects consisted of dizziness, light-headedness, nausea, and headache. No serious or unexpected adverse effects occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2211571 TI - The paradoxical stress response: a possible common basis for depression and other conditions. AB - This paper assumes that there are two types of stress-related pathology, the orthodox and the paradoxical, both depending on a positive feedback mechanism controlling the stress-related sympathetic discharge. The paradoxical stress response is speculated to be the common basis for a group of conditions, including depression, panic attacks, obesity, sexual deviations, alcoholism, and drug addiction. Evidence is provided that trazodone inhibits the stress-related sympathetic discharge. This would provide a rationale for its use not only in depression, but also in other conditions depending on an exaggeration of the orthodox or paradoxical stress response. PMID- 2211572 TI - The spectrum of mood disorders. AB - The problem of classifying mood disorders still lacks an acceptable solution. Interrater reliability studies have shown that this problem is more prevalent in mood disorders compared with other psychiatric conditions. Historically the problem originates from the distinction between Geisteskrankheiten and Gemutskrankheiten (mental and mood disorders) because the domain covered by the word mood has been progressively reduced. The fact that neurotic disorders are "emotional disorders" further complicates this field. The words anxiety and depression refer to a disorder, to a symptom, and to everyday feelings. A failure or difficulty in the distinction between these three meanings leads to nosological confusion. In recent years, the notion of a spectrum of mood disorders has gained acceptance. According to this, the diverse disorders are placed on a point that is more or less close to one of the extremes. Something similar occurs in the unipolar-bipolar distinction, in which the bipolar II or atypical and bipolar III occupy a central place on the spectrum. Cluster analysis and other mathematical techniques have helped to clarify the outlook, but there is a need for a biopsychosocial perspective and for a deeper understanding of the natural history of these disorders. PMID- 2211573 TI - Serotonin partial agonists in the treatment of depression. PMID- 2211574 TI - Depression and cerebral stroke. AB - Behavioral and psychological changes following cerebrovascular pathology have long been known. Depression, often severe and long-lasting, is a common and often unrecognized component of stroke. Although many of the clinical characteristics of poststroke depression have been reported in the literature for years, systematic studies of the frequency, course, relationship to lesion location, and response to treatment have only recently been undertaken. In this review, the authors briefly examine these various aspects of poststroke depression. PMID- 2211575 TI - Treatment of anxiety disorder in patients with mood disorders. AB - Symptoms compatible with a diagnosis of anxiety disorder frequently complicate the course of affective illness. Patients with depression may have panic attacks, phobias, severe social anxiety, obsessions, compulsions, and generalized anxiety. If the affective disorder is the primary condition, its treatment should be sufficient in most instances to relieve the concomitant anxiety symptoms. Thus, judicious choice of antidepressant therapy for treatment of major and atypical depression will usually resolve associated panic attacks, generalized anxiety, phobias, and compulsions. It must be recalled, however, that antidepressant therapy usually takes between 4 and 6 weeks to have full clinical effect; in the interim, anxiety symptoms may be the most troubling and disabling aspect of the illness. Therefore, using antianxiety agents in treating depressed patients who also have anxiety symptoms is often recommended while waiting for the antidepressant to work. Benzodiazepines are extremely useful for short-term treatment of most anxiety symptoms in depressed patients. The dose should be kept to the lowest possible to relieve symptoms, and the medication should be tapered and then discontinued once the underlying affective disturbance is relieved. Buspirone is also very effective in treating generalized anxiety disorder and may be used in conjunction with antidepressants of most classes. A wide range of behavioral and cognitive techniques may also help relieve anxiety symptoms in the depressed patient. PMID- 2211577 TI - Collagen gene expression and tooth development. An overview. AB - The regulation aspects of type I and type III collagen gene expression are examined and the relationships with tooth morphogenesis and differentiation are discussed. Type I and III collagens constitute the major molecular proteins of the dental tissues. In addition the collagen gene expression in the mesenchyme derived odontoblasts represents an important step in the cytodifferentiation at the mesenchymal level. Furthermore, odontoblasts seem to synthesize only type I and type I trimer collagens, but not type III collagen. Therefore, the aim of this overview is to describe the molecular mechanisms that control the expression of specific collagen genes during the process of odontoblast differentiation. The available data support the main transcriptional control and argue for the existence of an independent and developmental regulation during collagen gene expression in odontoblast cells. PMID- 2211576 TI - Changes in ultrastructural distribution of dental basement membrane heparan sulfate during early mouse tooth development. AB - With the invagination of the deep surface of the tooth buds of mouse embryos (15 days of gestation), heparan sulfate in the region of the lamina lucida of the dental basement membrane began to disappear. Subsequently, as the outline of the future dentino-enamel junction, which elaborates the molar cusp pattern, was formed (16-17 days of gestation), heparan sulfate disappeared not only in the lamina lucida but also at the external side of the lamina densa. However, prior to or during predentin matrix deposition (18 days of gestation), heparan sulfate reappeared in the dental basement membrane. PMID- 2211578 TI - In vivo morphogenetic activity of dentine matrix proteins. AB - Matrix proteins (EDTA-soluble and collagenase-released) from rabbit dentine have been demonstrated to show in vivo morphogenetic activity in exposed pulps of ferret canine teeth. In young adult ferrets, the reparative dentine resembled normal primary tubular dentine with odontoblast-like cells lining its formative surface. The reparative response in older animals was seen as osteo-dentine deposition. In both cases, the reparative response was characterized by its intensity within a comparatively short time period and also by the low grade or complete absence of any localized inflammatory response. Dentine matrix proteins implanted in exposed pulps of teeth provide a good experimental model for analysing the cell-matrix interactions and events taking place during odontoblast differentiation and dentinogenesis. PMID- 2211579 TI - The possible relationship between the mineralization of dentin and the composition of its organic matrix. AB - Using the rat incisor as a model, evidence is presented that enamel-related (ERD) and cementum-related (CRD) dentins exhibit differences in composition. Whereas the ERD is rich in highly phosphorylated phosphoproteins, the CRD is rich in lowly phosphorylated phosphoproteins. These differences are accompanied by and possibly related to differences in composition and physical properties of the mineral phase. PMID- 2211580 TI - Time-related changes in the distribution of 45Ca in the developing enamel of rat incisors as revealed by radioautography. AB - The distribution and movement of calcium through the enamel organ and into the forming enamel was examined by means of quantitative 45Ca radioautography in rat incisors. Dislocation of radiocalcium in the specimen was minimized during histologic and radioautographic processing by using rapid freeze/freeze substitution and dry emulsion coating methods. At 30 sec. after the 45Ca injection, distinct peaks of radioactivity occurred in the connective tissue immediately adjacent to the enamel organ and the infranuclear compartment of secretory ameloblasts. An intense labeling also occurred in the superficial layers of the forming enamel extending 15 microns below the surface. The grain density in the distal cytoplasm of secretory ameloblasts increased at later time periods, whereas all other regions of the enamel organ showed a considerable decrease in radioactivity. The radioactivity in the infranuclear compartment of ameloblasts with numerous mitochondria remained relatively high at 2 min. but was abolished by 10 min. after the injection. The grain density in the enamel matrix became much stronger but the labeled regions only extended to 20, 30, and 40 microns below the surface at 2, 10, and 60 min. after the injection, respectively. The application of wet emulsion over similarly prepared sections caused a severe dislocation of radiocalcium in the specimens. These data confirmed the rapid penetration of systemically administered radiocalcium into the surface layers of forming enamel and its slow diffusion to the deeper layers. The time-related changes in relative grain densities at various regions of the ameloblasts support the coexistence of a relatively slow transcellular pathway for calcium through the secretory ameloblast layer. PMID- 2211581 TI - Calcium transport in dentinogenesis. AB - A fundamental question in biomineralization research is the metabolism of the ionic constituents of the mineral phase. Mechanisms for the transport of Ca2+ ions have been identified and characterized in detail for various types of cells. Surprisingly little is known about osteoblasts and odontoblasts in this respect. This paper reviews what is known about calcium metabolism during dentinogenesis. PMID- 2211582 TI - Effects of nicotine on murine incisor development. AB - The effects of daily injections of nicotine sulfate on incisor development in CD I mice were studied. Pregnant animals, injected with 0.1% nicotine sulfate at a dose of 1.67 mg/kg body weight from the 6th to the 15th day of gestation, were sacrificed on the 18th postcoital day. The 130 nicotine treated fetuses, as well as the 348 control fetuses were embedded in paraffin and sectioned in the frontal plane. The developing incisors of the experimental fetuses were retarded, less differentiated, and reduced in breadth and length. The developing incisors of the control fetuses were in the early appositional stage of odontogenesis, whereas those of the experimental population were either in the late cap or early bell stage, depending on the presence or absence of palatal cleft, which occurred in 9.6% of the fetuses. PMID- 2211583 TI - Proceedings of the 4th workshop on tooth morphogenesis and development. Arc and Senans, France, May 30-June 2, 1990. PMID- 2211584 TI - Patterned distribution of differentiating dental cells: facts and hypotheses. AB - Differentiation of odontoblasts and ameloblasts occurs according to a tooth specific timing and spatial pattern. Both specific epigenesis and specific cell kinetics are involved. An integrated, simplified, working hypothesis explaining pattern formation is summarized. PMID- 2211585 TI - Enzyme inhibition by fluoro compounds. PMID- 2211586 TI - The progesterone receptor can regulate transcription in the absence of a functional TATA box element. AB - We have investigated the importance of the TATA box element in the induction of transcription by the progesterone receptor. Transcription was analyzed from promoters containing a steroid response element upstream of a wild-type or mutated TATA box. Mutation of the TATA box resulted in a loss of correctly initiated transcripts and abolished binding of TATA factor to the TATA box in vitro but did not inhibit transcriptional activation by the progesterone receptor. Thus we conclude that the receptor is able to stimulate the rate of transcription in the absence of a functional TATA box. PMID- 2211587 TI - Endocytosis and degradation of alpha 1-antitrypsin-protease complexes is mediated by the serpin-enzyme complex (SEC) receptor. AB - Alpha 1-Antitrypsin (alpha 1-AT) is similar to other members of the serine protease inhibitor (serpin) supergene family in that it undergoes structural rearrangement during the formation of a covalently stabilized inhibitory complex with its cognate enzyme, neutrophil elastase. We have recently demonstrated an abundant, high-affinity cell surface receptor on human hepatoma cells and human mononuclear phagocytes which recognizes a conformation-specific domain of the alpha 1-AT-elastase complex as well as of other serpin-enzyme complexes (Perlmutter, D. H., Glover, G. I., Rivetna, M., Schasteen, C. S., and Fallon, R. J. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 3753-3757). Binding to this serpin enzyme complex (SEC) receptor activates a signal transduction pathway for increased expression of the alpha 1-AT gene and may be responsible for clearance of serpin-enzyme complexes. In this study, we show that there is time-dependent and saturable internalization of alpha 1-AT-elastase and alpha 1-AT-trypsin complexes in human hepatoma HepG2 cells. Internalization is mediated by the SEC receptor as defined by inhibition by synthetic peptides corresponding to residues 359-374 of alpha 1-AT. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of intracellular radioactivity demonstrated that intact 75- and 66-kDa alpha 1-AT-trypsin complexes were internalized. Kinetic analysis of internalization at 37 degrees C showed that a single cohort of 125I-alpha 1-AT trypsin complexes, prebound to cells at 4 degrees C, disappeared from the cell surface and accumulated intracellularly within 5-15 min at 37 degrees C. The intracellular concentration of radiolabeled complexes then decreased rapidly coincident with appearance of acid-soluble degradation products in the extracellular culture fluid. Intracellular degradation was inhibited by internalization at 18 degrees C or by internalization at 37 degrees C in the presence of weak bases ammonium chloride, primaquine, and chloroquine, indicating that degradation is lysosomal. These results indicate that in addition to its role in signal transduction the SEC receptor participates in internalization and delivery of alpha 1-AT-protease complexes to lysosome for degradation. PMID- 2211588 TI - Is there a relationship between phosphatidylinositol trisphosphate and F-actin polymerization in human neutrophils? AB - Stimulation of human neutrophils with the chemoattractant N-formyl peptide caused rapid polymerization of F-actin as detected by right angle light scatter and 7 nitrobenz-2-oxa-1,3-diazol (NBD)-phallacidin staining of F-actin. After labeling neutrophils with 32P, exposure to N-formyl peptide induced a fast decrease of phosphatidylinositol 4-bisphosphate (PIP)2, a slow increase of phosphatidic acid, and a rapid rise of phosphatidylinositol 4-trisphosphate (PIP3). Formation of PIP3 as well as actin polymerization was near maximal at 10 s after stimulation. Half-maximal response and PIP3 formation at early time points resulted from stimulation of neutrophils with 0.01 nM N-formyl peptide or occupation of about 200 receptors. Sustained elevation of PIP3, prolonged right angle light scatter response, and F-actin formation required higher concentrations of N-formyl peptide, occupation of thousands of receptors, and high binding rates. When ligand binding was interrupted with an antagonist, F-actin rapidly depolymerized, transient light scatter response recovered immediately, and elevated [32P]PIP3 levels decayed toward initial values. However, recovery of [32P]PIP2 was not influenced by the antagonist. Based on the parallel time courses and dose response of [32P] PIP3, the right angle light scatter response, and F-actin polymerization, PIP3 is more likely than PIP2 to be involved in modulation of actin polymerization and depolymerization in vivo. PMID- 2211589 TI - Characterization of a new erythroid/megakaryocyte-specific nuclear factor that binds the promoter of the housekeeping human glycophorin C gene. AB - Human glycophorin C (GPC) is an integral membrane protein found in many cell types but which exhibits increased expression in red cells. We have investigated the in vitro binding of nuclear protein factors to the GPC gene 5'-flanking region which was transcriptionally active when transfected into erythroid and non erythroid cells. We found that in addition to known ubiquitous or erythroid trans acting factors, a presently uncharacterized erythroid/megakaryocyte-specific protein binds the GPC promoter. This factor, that we called NFE-6, is present in embryonic, fetal, or adult-like human or mouse erythroleukemic cell lines, in a megakaryoblastic cell line, but not in lymphoid or non-hematopoietic cell lines. These data suggest that NFE-6, like the well characterized NFE-1 factor, is tissue- but not stage-specific and is conserved across species. It is proposed that NFE-6 might be involved in the quantitative change in the expression of the house-keeping GPC gene related to red cell specialization. PMID- 2211590 TI - Irreversible inactivation of adenylyl cyclase by the "P"-site agonist 2',5' dideoxy-,3'-p-fluorosulfonylbenzoyl adenosine. AB - 2',5'-Dideoxy,3'-p-fluorosulfonylbenzoyl Adenosine (2',5'-dd3'-FSBA) was synthesized and found to be an agonist and affinity label for the "P"-site of adenylyl cyclase. This compound irreversibly inactivated both a crude detergent dispersed adenylyl cyclase from rat brain and the partially purified enzyme from bovine brain. The irreversible inactivation by 100 to 200 microM 2',5'-dd3'-FSBA was blocked in a concentration-dependent manner by several established P-site inhibitors of adenylyl cyclase, 2',5'-dideoxyadenosine, 2'-d3'-AMP, adenosine, and 2'-deoxyadenosine, but not by inosine, N6-(phenylisopropyl)adenosine, adenine, 2'-d3':5'-cAMP, or 5'-AMP, agents known not to act at the P-site. Moreover, irreversible inactivation by 2',5'-dd3'-FSBA occurred in the presence of ATP at concentrations up to 3 mM, making it unlikely that inactivation was due to an effect on the enzyme's catalytic site. Adenylyl cyclase was also irreversibly inactivated by 5'-FSBA, although modestly (less than 20%) and apparently nonspecifically. Dithiothreitol protected the enzyme from irreversible inactivation by 2',5'-dd3'-FSBA, but reversible inhibition of the enzyme was still observed, although with reduced potency. When 2 mM dithiothreitol was added after a 30-min preincubation with 2',5'-dd3'-FSBA, the rat brain enzyme was partially (approximately 80%) reactivated. The data suggest that 2',5'-dd3'-FSBA may irreversibly inactivate adenylyl cyclase by reacting with a cysteinyl moiety in proximity to the P-site domain of the enzyme. These data together with results of studies of P-site inhibition kinetics published elsewhere (Johnson, R. A., and Shoshani, I. (1990) J. Biol. Chem. 265, 11595-11600) strongly suggest that the P site and catalytic site are distinct domains on the enzyme. 2',5'-dd3'-FSBA, and especially its radiolabeled analog, should prove to be a useful probe for structural studies of adenylyl cyclase, particularly with regard to the P-site. PMID- 2211591 TI - Folding and aggregation of beta-lactamase in the periplasmic space of Escherichia coli. AB - High level expression of TEM beta-lactamase results in the accumulation of precursor and mature protein in the insoluble fraction of Escherichia coli. The mature polypeptide is sequestered in protein aggregates (inclusion bodies) located within the periplasmic space whereas the insoluble precursor is present in the cytoplasm. With the native beta-lactamase, aggregation is observed when the rate of expression exceeds 2.5% of the total protein synthesis rate. Substitution of the native signal sequence with the outer membrane protein A (OmpA) leader peptide results in extensive aggregation of only the mature protein. Furthermore, for OmpA-beta-lactamase, the accumulation of mature insoluble protein is independent of the rate of protein synthesis. These observations cannot be accounted by the kinetics of export of the OmpA-beta lactamase and the native precursor, therefore suggesting that the signal sequence affects the conformation of the newly secreted mature polypeptide and in turn, the folding pathway. Previously, we have shown that the aggregation of the mature protein secreted using its own signal sequence can be inhibited by growing the cells in the presence of non-metabolizable sugars such as sucrose (Bowden, G., and Georgiou, G. (1988) Biotechnol. Prog. 4, 97-101). We show here that this phenomenon is not related to osmotic effects, changes in beta-lactamase translation or precursor processing. It follows that the addition of sugars exerts a direct effect on the in vivo pathway of aggregation and folding, in analogy with the well characterized effect of sugars in vitro. PMID- 2211592 TI - Secretion in yeast of mutant human lysozymes with and without glutathione bound to cysteine 95. AB - A mutant human lysozyme C77A, in which Cys-77 is replaced with Ala, was secreted by Saccharomyces cerevisiae as two proteins (C77A-a and C77A-b) with different specific activities. A peptide fragment from Val93 to Ala108 was obtained from C77A-a by pepsin digestion, and examined by fast atom bombardment mass spectrometry and amino acid analysis. The results showed that glutathione was attached to the thiol group of Cys95 of the fragment through a disulfide linkage. This observation was confirmed by quantitative formation of free glutathionesulfonic acid from C77A-a by performic acid treatment. In contrast, there was no modification in the case of C77A-b. These results indicate that C77A a contained a mixed disulfide with glutathione attached to cysteine residue 95. In C77A-b, there appears to be a free thiol of Cys95 surrounded by many side chains, which was not modified by iodoacetic acid under native conditions, suggesting that the attachment of glutathione occurs during folding. These findings further suggest that in the oxidation step of disulfide bond formation in human lysozyme secreted by yeast, mixed disulfides are formed with glutathione and that posttranslational modification with glutathione can occur even in a protein secreted by yeast. PMID- 2211593 TI - Recombinant human extrinsic pathway inhibitor. Production, isolation, and characterization of its inhibitory activity on tissue factor-initiated coagulation reactions. AB - Previous studies have shown that extrinsic pathway inhibitor (EPI) is an effective inhibitor of factor Xa alone or factor VIIa-tissue factor complex in the presence of factor Xa. Since tissue factor exposure is implicated in thrombogenesis, we hypothesized that EPI may be valuable in the treatment of some thromboembolic episodes. Furthermore, EPI may be an important factor in bleeding complications in hemophiliacs. In the present study, human EPI was expressed in baby hamster kidney cells using a mammalian expression vector. Transfected cells expressed 1-2 micrograms/ml of recombinant EPI (rEPI) which was purified to homogeneity by heparin-Sepharose chromatography, ion-exchange chromatography, and reverse phase high performance liquid chromatography. Purified rEPI exhibited a specific activity of 30,000 units/mg and migrated as a single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular weight of 42,000. In addition, the NH2-terminal sequence of rEPI was identical to that of HepG2 EPI and HeLa EPI. The ability of rEPI to inhibit factor X activation by a complex of factor VIIa-tissue factor was then examined in the presence and absence of plasma concentrations of human factors VIII and IX. Using relipidated human brain tissue factor apoprotein, rEPI inhibited the factor VIIa mediated activation of factor X half-maximally at 2.5 and 1 nM in the presence and absence of factors VIII and IX, respectively. Using monolayers of a human bladder carcinoma cell line (J82) as the source of tissue factor, the activation of factor X by cell-bound factor VIIa was inhibited half-maximally by 5 nM rEPI in the presence of factors VIII and IX. The proteolytic activity of J82 cell bound factor Xa toward prothrombin was inhibited half-maximally at approximately 5 nM rEPI, while the amidolytic activity of factor Xa in solution was inhibited by rEPI with a Ki of 130 pM. Recombinant EPI also inhibited the amidolytic activity of factor VIIa half-maximally at 10 nM rEPI in the presence of relipidated tissue factor apoprotein and calcium. These results indicate that, in the presence of plasma concentrations of factors VIII and IX, at least 10 times the plasma concentration of EPI is required to reduce factor VIIa-dependent factor X activation one order of magnitude in vitro. In the absence of functional factor VIII and IX, rEPI at plasma levels was a potent inhibitor of factor VIIa mediated factor X activation, and this activity presumably accounts for the inability of hemophiliacs to initiate hemostasis via the extrinsic pathway. PMID- 2211594 TI - Mechanism of the inhibition of protein synthesis by vasopressin in rat liver. AB - A recent study reported that protein synthesis was inhibited in rat livers perfused with medium containing vasopressin (Chin, K. -V., Cade, C., Brostrom, M. A., and Brostrom, C. O. (1988) Int. J. Biochem. 20, 1313-1319). The inhibition of protein synthesis caused by vasopressin was associated with a disaggregation of polysomes, suggesting that peptide chain initiation was slowed relative to elongation. In contrast, Redpath and Proud (Redpath, N. T., and Proud, C. G. (1989) Biochem. J. 262, 69-75) recently reported an inhibition of peptide chain elongation by a calcium/calmodulin-dependent mechanism. Therefore, the question remained whether only peptide chain initiation was inhibited or both initiation and elongation were affected by vasopressin. In the present study, vasopressin was found to inhibit protein synthesis in both perfused rat livers and isolated rat hepatocytes. Ribosomal half-transit times in isolated hepatocytes averaged 1.9 +/- 0.1 min with or without vasopressin present in the media, demonstrating that the rate of peptide chain elongation was unaffected by vasopressin. Instead, the inhibition of protein synthesis induced by vasopressin was manifested at the level of peptide chain initiation. Vasopressin treatment resulted in both a 2 fold increase in the number of free ribosomal particles and a greater than 50% decrease in the amount of [35S]methionine bound to 43 S preinitiation complexes. In addition, the activity of eukaryotic initiation factor (eIF) 2B in crude extracts from perfused livers was reduced to 53% of the control value in response to vasopressin. The inhibition of eIF-2B activity was associated with an increase in the proportion of the alpha-subunit of eIF-2 in the phosphorylated form from 9.6% in control livers to 30.7% in livers perfused with medium containing vasopressin. The results demonstrate the novel finding that the inhibition of protein synthesis in vasopressin-treated livers is caused by a reduction in eIF 2B activity due to an increase in phosphorylation of eIF-2 alpha. PMID- 2211595 TI - Identification of the active site serine in pancreatic cholesterol esterase by chemical modification and site-specific mutagenesis. AB - Chemical modification and site-specific mutagenesis approaches were used in this study to identify the active site serine residue of pancreatic cholesterol esterase. In the first approach, purified porcine pancreatic cholesterol esterase was covalently modified by incubation with [3H]diisopropylfluorophosphate (DFP). The radiolabeled cholesterol esterase was digested with CNBr, and the peptides were separated by high performance liquid chromatography. A single 3H-containing peptide was obtained for sequence determination. The results revealed the binding of DFP to a serine residue within the serine esterase homologous domain of the protein. Furthermore, the DFP-labeled serine was shown to correspond to serine residue 194 of rat cholesterol esterase (Kissel, J. A., Fontaine, R. N., Turck, C. W., Brockman, H. L., and Hui, D. Y. (1989) Biochim. Biophys. Acta 1006, 227 236). The codon for serine 194 in rat cholesterol esterase cDNA was then mutagenized to ACT or GCT to yield mutagenized cholesterol esterase with either threonine or alanine, instead of serine, at position 194. Expression of the mutagenized cDNA in COS-1 cells demonstrated that substitution of serine 194 with threonine or alanine abolished enzyme activity in hydrolyzing the water-soluble substrate, p-nitrophenyl butyrate, and the lipid substrates cholesteryl [14C]oleate and [14C] lysophosphatidylcholine. These studies definitively identified serine 194 in the catalytic site of pancreatic cholesterol esterase. PMID- 2211596 TI - Purification and substrate specificity of heparitinase I and heparitinase II from Flavobacterium heparinum. Analyses of the heparin and heparan sulfate degradation products by 13C NMR spectroscopy. AB - The purification of two heparitinases and a heparinase, in high yields from Flavobacterium heparinum was achieved by a combination of molecular sieving and cation-exchange chromatography. Heparinase acts upon N-sulfated glucosaminido-L iduronic acid linkages of heparin. Substitution of N-sulfate by N-acetyl groups renders the heparin molecule resistant to degradation by the enzyme. Heparitinase I acts on N-acetylated or N-sulfated glucosaminido-glucuronic acid linkages of the heparan sulfate. Sulfate groups at the 6-position of the glucosamine moiety of the heparan sulfate chains seem to be impeditive for heparitinase I action. Heparitinase II acts upon heparan sulfate producing disulfated, N-sulfated and N acetylated-6-sulfated disaccharides, and small amounts of N-acetylated disaccharide. These and other results suggest that heparitinase II acts preferentially upon N,6-sulfated glucosaminido-glucuronic acid linkages. The total degradation of heparan sulfate is only achieved by the combined action of both heparitinases. The 13C NMR spectra of the disaccharides formed from heparan sulfate and a heparin oligosaccharide formed by the action of the heparitinases are in accordance to the proposed mode of action of the enzymes. Comparative studies of the enzymes with the commercially available heparinase and heparitinase are described. PMID- 2211597 TI - Bovine heart pyruvate dehydrogenase kinase stimulation by alpha-ketoisovalerate. AB - Purified bovine heart pyruvate dehydrogenase complex was used to investigate the effects of monovalent cations and alpha-ketoisovalerate on pyruvate dehydrogenase (PDH) kinase inhibition by thiamin pyrophosphate. Initial velocity patterns for thiamin pyrophosphate inhibition were consistent with hyperbolic non-competitive or hyperbolic uncompetitive inhibition at various K+ concentrations between 0 and 120 mM. The Kis, Kid, and Kin for thiamin pyrophosphate were in the range of 0.009 to 5.1 microM over the range of K+ concentrations tested. In the absence of K+, 1 mM alpha-ketoisovalerate had no effect on PDH kinase inhibition by thiamin pyrophosphate, whereas in the presence of 20 mM K+, alpha-ketoisovalerate stimulated PDH kinase activity almost 2-fold over the range of 0-80 microM thiamin pyrophosphate. Half-maximal stimulation by alpha-ketoisovalerate occurred at about 200 microM in the presence of 100 microM thiamin pyrophosphate and 20 mM K+. Similar but less extensive changes occurred in the presence of 100 microM thiamin pyrophosphate and 1 mM NH4+. Initial velocity patterns for PDH kinase inhibition by thiamin pyrophosphate in the presence of 2 mM alpha-ketoisovalerate were mixed noncompetitive, but alpha-ketoisovalerate increased the Vm and Km for adenosine 5'-triphosphate in the presence of inhibitor. In the presence of thiamin pyrophosphate, PDH kinase remained stimulated after chromatography on Sephadex G-25 to remove alpha-ketoisovalerate. The results indicate that acylation of pyruvate dehydrogenase complex by alpha-ketoisovalerate results in PDH kinase stimulation but only in the presence of monovalent cations and thiamin pyrophosphate. PMID- 2211598 TI - Glucose regulates glucokinase activity in cultured islets from rat pancreas. AB - In this study, we have used isolated pancreatic islets cultured for 7 days in 3 or 30 mM glucose to explore whether glucokinase is induced or activated by high glucose concentrations and has related enzyme activity to glucose-stimulated insulin release. Islets cultured in low glucose medium or low glucose medium plus 350 ng/ml insulin did not respond to high glucose stimulation. Islets cultured in medium containing high glucose concentrations showed a high rate of basal insulin secretion when perifused with 5 mM glucose, and the insulin release was greatly augmented in a biphasic secretion profile when the glucose concentration was raised to 16 mM. Islet glucokinase and hexokinase activities were determined by a sensitive and specific fluorometric method. Glucokinase activity was reduced to approximately 50% in islets cultured in low glucose medium with or without insulin present compared to results with fresh islets. However, islets cultured in 30 mM glucose showed that glucokinase activity was elevated to 236% compared to results with fresh islets. It is concluded that (a) glucose is the physiological regulator of glucokinase in the islet of Langerhans and that (b) the activity of glucokinase plays a crucial role in glucose-induced insulin secretion. PMID- 2211599 TI - 1,2-Diacylglycerol and ceramide levels in insulin-resistant tissues of the rat in vivo. AB - Phorbol esters have been reported to decrease sensitivity or responsiveness to insulin in cells in vitro. Since phorbol esters are analogues of endogenously produced 1,2-diacylglycerol, the present study investigated whether 1,2 diacylglycerol concentration is elevated in insulin-resistant tissues of the rat in vivo. Studies were done on 11-12-week-old genetically obese Zucker rats, which are insulin-resistant. Lean Zucker rats served as controls. Levels of 1,2 diacylglycerol in obese rats were increased 82% in liver, 136% in calf muscles, 72% in soleus muscle, a slow-twitch muscle, and 40% in plantaris muscle, a fast twitch muscle. Ceramide levels in the same tissues were increased 26, 52, 69, and 13%, respectively. Studies were also done on normal, non-obese Sprague-Dawley rats 3 h, 1, 3, 8, and 15 days after interrupting the nerve supply to hindlimb muscles. We have previously shown that 3-17 days after denervation, soleus muscles are completely unresponsive to insulin and do not increase glucose uptake in response to insulin stimulation in vivo, whereas plantaris muscles show a normal glucose uptake when stimulated by insulin; however, the insulin-induced increment in glucose uptake is reduced 68% because it is superimposed on already elevated basal glucose uptake (Turinsky, J. (1987) Am. J. Physiol. 252, R531 R537). In the present study, the denervated soleus muscles exhibited a sustained increase of 23-56% in 1,2-diacylglycerol concentration between 3 h and 15 days after interruption of nerve supply. The denervated soleus muscles also showed 34 and 42% increases in ceramide concentration at 3 and 8 days after denervation, respectively. In contrast, no increases in 1,2-diacylglycerol concentration were observed in plantaris muscles at shorter intervals than 15 days after denervation. Ceramide concentrations in plantaris muscles were increased 43 and 75% at 8 and 15 days after denervation, respectively. These observations demonstrate that tissue insulin resistance is frequently associated with a long term increase in tissue 1,2-diacylglycerol concentration. This suggests the possibility that augmented 1,2-diacylglycerol levels contribute to the development of some types of tissue insulin resistance. PMID- 2211600 TI - Conversion of 5-S-methyl-5-thio-D-ribose to methionine in Klebsiella pneumoniae. Stable isotope incorporation studies of the terminal enzymatic reactions in the pathway. AB - Extracts of Klebsiella pneumoniae convert 5-S-methyl-5-thio-D-ribose (methylthioribose) to methionine and formate. To probe the terminal steps of this biotransformation, [1-13C]methylthioribose has been synthesized and its metabolism examined. When supplemented with Mg2+, ATP, L-glutamine, and dioxygen, cell-free extracts of K. pneumoniae converted 50% of the [1-13C]methylthioribose to [13C]formate. The formation of [13C]formate was established by 13C and 1H NMR spectroscopy studies of the purified formate, and by 13C and 1H NMR spectroscopy and mass spectrometry studies of its p-phenylphenacyl derivative. By contrast, no incorporation of label from [1-13C]methylthioribose into the biosynthesized methionine was detected by either mass spectrometry or 13C and 1H NMR spectroscopy. The most reasonable interpretation of these results is that C-1 of methylthioribose is converted directly to formate concomitant with the conversion of carbon atoms 2-5 to methionine. The penultimate step in the conversion of methylthioribose to methionine and formate is an oxidative carbon-carbon bond cleavage reaction in which an equivalent of dioxygen is consumed. To investigate the fate of the dioxygen utilized in this reaction, the metabolism of [1 13C]methylthioribose in the presence of 18O2 was also examined. Mass spectrometry revealed the biosynthesis of substantial amounts of both [18O1]methionine and [13C, 18O1]formate under these conditions. These results suggest that the oxidative transformation in the conversion of methylthioribose to methionine and formate may be catalyzed by a novel intramolecular dioxygenase. A mechanism for this dioxygenase is proposed. PMID- 2211601 TI - Purification and identification of dTDP-oleandrose, the precursor of the oleandrose units of the avermectins. AB - The nucleotide sugar precursor of the oleandrose units of the avermectins has been purified from a mutant of Streptomyces avermitilis, which does not synthesize any avermectins but which converts avermectin aglycones to their respective disaccharides. This precursor has been identified as dTDP-oleandrose. The purification was achieved by anion exchange and reverse phase high performance liquid chromatography. The purified nucleotide sugar had an absorption spectra characteristic of thymidine, released dTMP when treated with phosphodiesterase, and possessed an NMR spectrum in which three resonances characteristic of oleandrose were seen in addition to the thymidine signals. The enzyme, avermectin aglycone dTDP-oleandrose glycosyltransferase, which catalyzes the stepwise addition of oleandrose to the avermectin aglycones, has been demonstrated in cell-free extracts and (NH4)2SO4 fractions of cell-free extracts of S. avermitilis. The enzyme is specific for dTDP-oleandrose as the glycosyl donor but utilizes all avermectin aglycones as glycosyl acceptors. The stoichiometry between dTDP-oleandrose consumed in the reaction and oleandrose units transferred to the avermectin mono- and disaccharide was found to be 1:1. PMID- 2211602 TI - The yeast fatty acid synthase. Pathway for transfer of the acetyl group from coenzyme A to the Cys-SH of the condensation site. AB - The reaction pathway of enzyme-catalyzed acetylation of the acyl-accepting sites of the yeast synthase, a Ser-OH at the acetyl transacylase site, a Cys-SH at the beta-ketoacyl synthase site, and the acyl carrier protein 4'-phosphopantetheine SH (Pant-SH), has been investigated using the chromophoric substrate, p nitrophenyl thioacetate. The stoichiometry of acetylation of the native enzyme was 3 mol of acetate bound per mol of synthase unit, alpha beta (Mr 430,000). The acetylation process is biexponential; the rate constant of acetylation of the first 2 mol is 5.0 s-1 and the third mol is 0.2 s-1. The pathway by which acetyl moiety is added to the enzyme was determined by selectively blocking the acyl accepting sites and subsequently determining the kinetics and stoichiometry of acetylation. The dibromopropanone-treated enzyme, in which the Pant-SH and Cys-SH are alkylated, exhibited an exponential burst of approximately 1 mol/mol of synthase unit with a rate constant of 11.0 s-1. The iodoacetamide-treated enzyme, in which Cys-SH is alkylated, had a biexponential burst with a total stoichiometry of approximately 2 mol/mol of synthase unit, with rate constants of 9 and 0.2 s-1, respectively. The kinetically competent acetylation to the extent of 2 and approximately 1 mol/mol of synthase unit for both Cys-SH and Cys-SH and Pant-SH-blocked enzymes, respectively, indicated that the route of acetyl transfer in the yeast synthase is obligatorily Ser-OH----Cys-SH. The acetylation of Pant-SH (0.2 s-1) occurs with a rate insignificant to the process of fatty acid synthesis (turnover rate constant of 1.5 s-1). These conclusions are supported by experiments involving end point radiolabeling of the synthase with [1-14C]acetyl moieties using the substrate, p-nitrophenyl thio[1-14C]acetate. Native, dibromopropanone-treated, and iodoacetamide-treated enzymes bind about 3, 1, and 2 mol of acetyl/mol of synthase unit, respectively. Performic acid oxidation studies of the acetyl-labeled enzyme indicate that there is one Ser-O acetyl formed in the native and alkylated enzymes and one Cys-S-acetyl and one Pant-S-acetyl formed in the native enzyme. Altogether, these results support our contention that the acetylation of the Pant-SH is kinetically incompetent. Thus, the yeast synthase transacetylation reactions occur by a novel process of acetyl transfer from CoA to Ser-OH----Cys-SH, which is in contrast to the transfer from CoA to Ser-OH----Pant-SH----Cys-SH catalyzed by the prokaryotic synthases.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2211603 TI - Ultraviolet-visible transient spectroscopy of bacteriorhodopsin mutants. Evidence for two forms of tyrosine-185----phenylalanine. AB - The photocycle kinetics of the bacteriorhodopsin mutant Tyr-185----Phe has been investigated by UV-visible transient spectroscopy. Flash-induced spectral changes were measured from 100 ns to 500 ms using a gated optical multichannel analyzer on protein samples that were reconstituted in vesicles with Halobacterium halobium lipids. Tyr-185----Phe exhibits a pH-dependent absorbance spectrum reflecting contributions from two different species. At pH 6, the dominant photocycling species has a lambda max near 610 nm although the absorption maximum of light-adapted Tyr-185----Phe is at 581 nm. This red-shifted species does not form any M-like intermediate and undergoes a photocycle similar to that observed for deionized blue membrane. At pH 8, the dominant photoactive form exhibits a lambda max near 550 nm. This purple species, which is blue shifted 20 nm relative to wild-type bacteriorhodopsin, exhibits a photocycle similar to the wild type. However, M formation occurs in 8 microseconds, approximately three times faster than wild-type bacteriorhodopsin at pH 8. In addition, an unusually long lived intermediate absorbing at 610 nm is observed at high pH. In the UV region, a broad band near 300-310 nm is absent in the mutant relative to wild type, consistent with earlier measurements made at low temperature which suggest that Tyr-185 undergoes a change in protonation. Steady-state proton pumping action spectra indicate that the 550 nm species does transport protons but that the blue species is inactive. These results are discussed in terms of a model that hypothesizes that Tyr-185 is located close to the bacteriorhodopsin chromophore and stabilizes the interaction of helices F and G through formation of a polarizable bond with Asp-212. PMID- 2211604 TI - Vibrational spectroscopy of bacteriorhodopsin mutants. Evidence for the interaction of aspartic acid 212 with tyrosine 185 and possible role in the proton pump mechanism. AB - The role of Asp-212 in the proton pumping mechanism of bacteriorhodopsin (bR) has been studied by a combination of site-directed mutagenesis and Fourier transform infrared difference spectroscopy. Difference spectra were recorded at low temperature for the bR----K and bR----M photoreactions of the mutants Asp-212--- Glu, Asp-212----Asn, and Asp-212----Ala. Despite an increased proportion of the 13-cis form of bR (normally associated with dark adaptation), all of the mutants exhibited a light-adapted form containing as a principal component the normal all trans retinal chromophore. The absence of a shift in the retinal C = C stretching frequency in these mutants indicates that Asp-212 is not a major determinant of the visible absorption wavelength maximum in light-adapted bR. It is unlikely that Asp-212 is the acceptor group for the Schiff base proton since both the Asp 212----Glu and Asp-212----Ala mutants formed an M intermediate. All of the Asp 212 mutants were missing a Fourier transform infrared difference band that had been assigned previously to protonation changes of Tyr-185. These results are discussed in terms of a model in which Tyr-185 and Asp-212 form a polarizable hydrogen bond and are positioned near the C13-Schiff base portion of the chromophore. These 2 residues may be involved in stabilizing the relative orientation of the F and G helices and isomerizing the retinal in a regioselective manner about the C13 = C14 double bond. PMID- 2211605 TI - 4-alkyl-o-quinone/2-hydroxy-p-quinone methide isomerase from the larval hemolymph of Sarcophaga bullata. I. Purification and characterization of enzyme-catalyzed reaction. AB - An enzyme which catalyzes the conversion of certain 4-alkyl-o-benzoquinones to 2 hydroxy-p-quinone methides has been purified to apparent homogeneity from the hemolymph of Sarcophaga bullata by employing conventional protein purification techniques. The purified enzyme migrated with an approximate molecular weight of 98,000 on gel filtration chromatography. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, it migrated as a single band with a molecular weight of 46,000, indicating that it is made up of two identical subunits. It exhibited a pH optimum of 6.0 and readily converted chemically synthesized as well as enzymatically generated quinones derived from N-acetyldopamine, N-beta alanyldopamine, and 3,4-dihydroxyphenethyl alcohol to highly unstable 2-hydroxy-p quinone methides. The quinone methides thus formed were rapidly and nonenzymatically hydrated to form side chain hydroxylated o-diphenols as the stable product. In support of this proposition, when the enzyme reaction with N acetyldopamine quinone was conducted in the presence of 10% methanol, racemic beta-methoxy-N-acetyldopamine was recovered as an additional product. The quinones of N-acetylnorepinephrine, N-beta-alanylnorepinephrine, and 3,4 dihydroxyphenylglycol were also attacked by the isomerase, resulting in the formation of N-acetylarterenone, N-beta-alanylarterenone and 2-hydroxy-3',4' dihydroxyacetophenone, respectively as the stable products. The isomerase converted the dihydrocaffeiyl methyl amide quinone to its quinone methide analog which rapidly tautomerized to yield caffeiyl methyl amide. The importance of quinone isomerase in insect immunity and sclerotization of insect cuticle is discussed. PMID- 2211606 TI - Evidence for a close link between the thyroid hormone transport system and the aromatic amino acid transport system T in erythrocytes. AB - The transport of [125I]triiodothyronine ([125I]T3) and [3H]tryptophan ([3H]Trp) by washed rat erythrocytes was studied at 25 degrees C in the presence of leucine in order to block the neutral amino acid transport system L. Eadie-Hofstee plots of initial velocity data gave the following values of Km (micromolar) and Vmax (nanomole/min/10(8) cells): 0.122 +/- 0.007 and 0.140 +/- 0.021 for T3, and 558 +/- 28 and 17.4 +/- 2.3 for Trp (n = 5). The Trp transport system in rat erythrocytes is similar to the human erythrocyte aromatic amino acid-specific system T described by Rosenberg et al. (Rosenberg, R., Young, J. D., and Ellory, J. C. (1980) Biochim. Biophys. Acta 598, 375-384). Unlabeled aromatic amino acids (e.g. Trp, phenylalanine, tyrosine) competitively inhibited [125I]T3 uptake and unlabeled iodothyronine analogues (e.g. T3, D-T3, thyroxine, thyronine) competitively inhibited [3H]Trp uptake. The inhibition constants of these competitors measured with each labeled substrate were highly correlated. N Ethylmaleimide irreversibly inhibited T3 and Trp transport and each substrate protected the transport system of the other from inactivation by N ethylmaleimide. The Vmax of T3 and Trp transport by human erythrocytes were 500 and 120 times lower, respectively, than those of rat erythrocytes (0.30 and 126 pmol/min/10(8) cells, respectively). The T3 and Trp transport activities of sheep erythrocytes were undetectable. These results indicate that T3 and Trp either share a common multi-specific transport system or are transported by closely linked systems which interact in the erythrocyte membrane. PMID- 2211607 TI - Sterol-mediated regulation of mevalonic acid synthesis. Accumulation of 4 carboxysterols as the predominant sterols synthesized in a Chinese hamster ovary cell cholesterol auxotroph (mutant 215). AB - Chinese hamster ovary-215 (CHO-215) mutant cells are auxotrophic for cholesterol. Berry and Chang (Berry, D. J., and Chang, T. Y. (1982) Biochemistry 21, 573-580) suggested that the metabolic lesion was at the level of 4-methyl sterol oxidation. However, the observed cellular accumulation of lanosterol was not consistent with a defect at this metabolic site. With the use of a novel Silica Sep Pak sterol separation procedure, we demonstrated that 60-80% of the acetonesoluble lipid radioactivity in [5-3H]mevalonate-labeled CHO-215 cells was incorporated into acidic sterols. 7(8),Cholesten-4 beta-methyl,4 alpha-carboxy,3 beta-ol was the dominant end product. In addition to this acidic sterol, 7(8),24 cholestadien,4 beta-methyl,4 alpha-carboxy,3 beta-ol and 7(8),24-cholestadien,4 alpha-carboxy,3 beta-ol were also isolated. Incubation of cell-free extracts with [3H]7(8)-cholesten-4 beta-methyl, 4 alpha-carboxy,3 beta-ol and pyridine nucleotides confirmed that CHO-215 4-carboxysterol decarboxylase activity was less than 1% of that for wild type cells. Thus, a correspondence between decreased 4-carboxysterol decarboxylase activity and the spectrum of accumulated sterol products by intact CHO-215 cells was demonstrated. No detectable cholesterol was synthesized by CHO-215 cells. 3H-Product accumulation studies demonstrated that 7(8),24-cholestadien, 4 beta-methyl,4 alpha-carboxy,3 beta-ol increased prior to its subsequent saturation at the delta 24 carbon. Furthermore, the steady state ratio for delta 24-saturated acidic sterols/unsaturated acidic sterols was dependent on media cholesterol source and amount. Finally, the accumulated acidic sterol(s) were not regulatory signal molecules for the modulation of 3-hydroxy-3-methyl-glutaryl coenzyme. A reductase activity in response to cholesterol availability. PMID- 2211608 TI - Identification of a major iodolipid from the horse thyroid gland as 2 iodohexadecanal. AB - The incorporation of iodide into proteins (PBI) and lipids (LBI) of horse thyroid slices was measured in various conditions. Their dependency on the concentration of extracellular iodide was strikingly different. For PBI the relationship was biphasic with a decrease above 10 microM, likely to correspond to the Wolff Chaikoff effect. On the contrary, LBI increased as a function of iodide concentration up to 100 microM. Methimazole (MMI) inhibited the incorporation of iodide into both LBI and PBI, but higher concentrations of MMI were required to depress LBI as compared to PBI. The inhibition of active iodide transport by NaCIO4 reduced both PBI and LBI. Chromatography on silica gel resolved almost equal amounts of low and high polarity iodolipids. The main unpolar iodolipid was identified as 2-iodohexadecanal (2-IHDA), on the basis of proton nuclear magnetic resonance spectroscopy, mass spectrometry, and co-elution with authentic 2-IHDA obtained by chemical synthesis in reversed-phase high performance liquid chromatography and gas chromatography. The presence of 2-IHDA was also detected in dog thyroid slices, following incubation with KI (50 microM) and in the rat thyroid, 4 hours after intraperitoneal injection of KI (650 micrograms). An incubation of bovine brain plasmalogens with lactoperoxidase, iodide, and H2O2 generated 2-IHDA. In conclusion, we have identified a major thyroid iodolipid as 2-iodohexadecanal. The biosynthesis of this compound is likely to involve the addition of iodine to the vinyl ether group of plasmalogens. PMID- 2211609 TI - A potent and selective photoaffinity probe for the anti-estrogen binding site of rat liver. AB - The anti-estrogen binding site (ABS) is an apparently ubiquitous component of cells that has been shown to be intimately linked with the antiproliferative effects of certain antiestrogenic compounds, like tamoxifen, which is currently used for the treatment of breast cancer. However, the identification and in vitro study of this novel protein has been hampered to date by a lack of convenient probes that will efficiently label the molecule in nonpurified preparations. Thus, using a selective ABS ligand (4-benzylphenoxy-N-ethylmorpholine, MBPE) as starting material, we synthesized a photosensitive azido derivative, [(2-azido-4 benzyl)phenoxy]N-ethylmorpholine (azido-MBPE) that can be prepared in a tritiated form. Azido-MBPE has a high affinity for ABS (Kd = 3 nM), identical to that of tamoxifen, and covalently labels 5 and 12% of membrane-bound and detergent solubilized ABS, respectively. Its incorporation is selectively and competitively inhibited by other ABS ligands (tamoxifen greater than nitromifen greater than hydroxytamoxifen). [3H]Azido-MBPE potently photolabels either membrane-bound or detergent-solubilized ABS as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under denaturing conditions revealing specific photoincorporation in a protein band of Mr = 40,000. This molecular weight is approximately two times lower than what we observed previously for ABS preparations studied under nondenaturing conditions and postlabeled with [3H]tamoxifen (Mr = 80,000-110,000). In chromatofocusing experiments with photolabeled ABS, a single specifically labeled protein fraction migrating with a pI of 6.4 was found to exhibit a Mr of 40,000 when subsequently electrophoresed on sodium dodecyl sulfate-polyacrylamide gels. These results indicate that [3H]azido-MBPE is a specific high affinity probe of ABS that will prove useful in the ultimate identification of this protein. PMID- 2211610 TI - recA protein filaments bind two molecules of single-stranded DNA with off rates regulated by nucleotide cofactor. AB - To probe the role of nucleotide cofactor in the binding of single-stranded DNA to recA protein, we have developed a sedimentation assay using 5'-labeled 32P poly(dT).recA.poly(dT) complexes sediment quantitatively when centrifuged at 100,000 x g for 45 min, whereas free poly(dT) remains in the supernatant. In the presence of ATP, between 6 and 7 bases cosediment per recA monomer; but when ADP is present or in the absence of added nucleotide cofactor, only 3-3.5 bases/recA monomer cosediment. In competition experiments in which recA.32P-poly(dT) complexes are incubated with unlabeled poly(dT), we again find 3-3.5 bases of labeled poly(dT) cosedimenting per recA monomer when no nucleotide cofactor is present. However, when the same experiment is performed with ATP, only half of the expected 6-7 bases of labeled poly(dT) remain bound to the DNA, demonstrating that half of the poly(dT) in the complex exchanges rapidly with free poly(dT), whereas the other half equilibrates slowly, like poly(dT) in the absence of nucleotide. The rate of exchange of the second more tightly bound poly(dT) is accelerated when ADP is present. Our observations are rationalized by a model in which each recA protein helical filament binds two strands of poly(dT) with a stoichiometry of 3-3.5 bases/recA monomer/strand. PMID- 2211611 TI - Two soluble forms of bovine carboxypeptidase H have different NH2-terminal sequences. AB - Carboxypeptidase H is an important enzyme in the biosynthesis of many peptide hormones. Development of a rapid isolation procedure led to the purification of two soluble forms from acidic extracts of bovine pituitary glands. These two forms differed in apparent molecular size (56 and 53 kDa). Both forms were found in the anterior lobe while only the 53-kDa form was found in posterior lobe. Digestion with N-glycosidase F demonstrated that these two forms are not due to alternative glycosylation of a common polypeptide core. Both forms bind antibodies raised against a COOH-terminal peptide of the full-length protein showing that the difference between them is not due to proteolysis at the COOH terminus. These results also argue against the idea that proteolysis of COOH terminal domains converts the membrane-associated form of this protein into a soluble form. NH2-terminal sequence analysis demonstrated different NH2 termini. The NH2-terminal sequence of the 56-kDa form begins at the site predicted for signal peptide cleavage. Ion-exchange chromatography resolved the 56-kDa form from the 53-kDa form. The two forms were catalytically active with very similar properties. These results show that bovine carboxypeptidase H can be posttranslationally processed at alternative sites and provide evidence against the idea of a prosequence that must be removed before enzyme activity can be expressed. PMID- 2211612 TI - Ribozymes correctly cleave a model substrate and endogenous RNA in vivo. AB - The alpha-sarcin domain of 28 S RNA in Xenopus oocytes is attacked by several catalytic toxins (e.g. alpha-sarcin and ricin) that abolish protein synthesis. We synthesized 6 ribozymes targeted to the alpha-sarcin domain and to an oligoribonucleotide (34-mer) that mimics this domain. Sarcin ribozyme 5 (SR5) efficiently cleaved after the CUC site in the synthetic 34-mer in vitro at 50 degrees C. SR5 also cut the same site when both substrate and ribozyme were coinjected or injected separately into oocytes at 18 degrees C. Correct cleavage in vivo was shown by isolating and sequencing the large cleavage fragment. The cleavage reaction appeared to function equally well in the oocyte nucleus and cytoplasm. SR5 also correctly cleaved endogenous 28 S RNA in oocytes, although cutting was much less efficient than with alpha-sarcin. We therefore demonstrated that a ribozyme specifically cuts both a model substrate and a cellular RNA in vivo. Earlier work showed that certain injected deoxyoligonucleotides complementary to the alpha-sarcin region abolish protein synthesis. Oocyte protein synthesis was also abolished by an SR5 containing a single G----U substitution that inactivates RNA catalysis, indicating that SR5's translational suppression was perhaps due to antisense function rather than ribozyme cleavage. PMID- 2211613 TI - Isolation, characterization, and expression of cDNA encoding a rat liver endoplasmic reticulum alpha-mannosidase. AB - We have isolated a cDNA encoding an endoplasmic reticulum alpha-mannosidase, an asparagine-linked oligosaccharide processing enzyme, from a rat liver lambda gt11 library. Two degenerate oligonucleotides, based on amino acid sequence data from the purified enzyme, were used as primers in the polymerase chain reaction with liver cDNA as a template to generate an unambiguous cDNA probe. The cDNA fragment (524 base pair) obtained was then used to isolate cDNA clones by hybridization. We isolated two overlapping clones which were used to construct a full-length cDNA of 3392 base pairs. A single open reading frame of 1040 amino acids encodes a protein with a molecular mass of 116 kilodaltons containing the six known peptide sequences. The deduced amino acid sequence revealed no classical signal sequence or membrane-spanning domain. The alpha-mannosidase encoding cDNA can be expressed transiently in COS cells using the mammalian expression vector pXM, causing a 400-fold increase in alpha-mannosidase activity as well as a dramatic increase in immunoreactive polypeptide. The rat liver endoplasmic reticulum alpha mannosidase bears striking homology to the vacuolar alpha-mannosidase from Saccharomyces cerevisiae. PMID- 2211614 TI - Protein secretion in gram-negative bacteria. The extracellular metalloprotease B from Erwinia chrysanthemi contains a C-terminal secretion signal analogous to that of Escherichia coli alpha-hemolysin. AB - The secretion signal of extracellular metalloprotease B that is secreted without a signal peptide by the Gram-negative phytopathogenic bacterium Erwinia chrysanthemi is shown by deletion and gene fusion analyses to be located within the last 40 C-terminal amino acids. Secretion of a peptide containing only this region of the protease requires the same three secretion factors (PrtD, PrtE, and PrtF) that were previously shown to be required for the secretion of the full length protease. This secretion signal can also be recognized, albeit inefficiently, by the analogous secretion machinery of alpha-hemolysin, another protein with a C-terminal secretion signal that is secreted by some strains of the Gram-negative bacterium Escherichia coli. The secretion signal was fused to an internal 200-amino acid fragment from the sequence of the cytoplasmic protein amylomaltase to promote its specific secretion by the protease secretion pathway. Almost exactly the same sequence as that identified as the protease B secretion signal was also found at the C terminus of metalloprotease C that is also secreted by E. chrysanthemi. PMID- 2211615 TI - cDNA sequence of the human integrin beta 5 subunit. AB - A novel integrin receptor involved in cell adhesion to the matrix protein vitronectin has recently been described from a human lung epithelial-derived cell line (Cheresh, D. A., Smith, J. W., Cooper, H. M., and Quaranta, V. (1989) Cell 57, 59-69). This receptor has an alpha subunit that appears identical to the alpha v of the vitronectin receptor alpha v beta 3 expressed in melanoma and endothelial cells, but is complexed with a distinct beta subunit, beta 5. cDNA clones coding for beta 5 have been isolated and used to determine the mRNA and amino acid sequence of this new subunit. A 3.3-kilobase mRNA was found to code for a mature protein of 775 amino acid residues with a hydrophobic leader sequence of 24 amino acids. A 56% identity was found between the beta 5 and beta 3 protein sequences, making them the most closely related of the integrin beta subunits. Polymerase chain reaction abundance analysis revealed that alpha v and beta 5 mRNAs were found in seven very different cell lines, compared with beta 3 mRNA which was found in only three of the them, indicating that this new integrin receptor may be widely distributed. PMID- 2211616 TI - Functional characterization of human platelet-released factor V and its activation by factor Xa and thrombin. AB - The functional characterization of human platelet-released factor V and its activation by factor Xa and thrombin was studied by functional assessment of cofactor activity and Western blotting analyses of platelet releasates, obtained by stimulating washed suspensions of platelets with various agonists, including collagen, collagen with ADP, and the calcium ionophore A23187. Platelet factor V was released as a partially proteolyzed molecule that was bound to platelet microparticles, irrespective of the agonist used. Radiolabeled plasma factor V was not cleaved for up to 30 min following release when added to platelets prior to stimulation, suggesting that platelet factor V was stored in a partially proteolyzed form. Released platelet factor V possessed significant cofactor activity that was increased only 2-3-fold by either factor Xa or thrombin. The factor V subunits that expressed cofactor activity were isolated and found to consist of peptides of Mr = 220,000 and 150,000. Incubation of released platelet factor V with factor Xa or thrombin yielded the same cleavage pattern, in which two peptides of Mr = 105,000 and 74,000 appeared to be electrophoretically indistinguishable from thrombin-activated plasma factor V. Under the conditions of these studies, factor Xa activated platelet-released factor V 50-100 times more effectively than thrombin. This observation may be due in part to the existence of platelet factor V in a partially proteolyzed state, or its association with platelet microparticles following platelet stimulation. These data collectively suggest that platelet-released factor V may be the foremost initiator of prothrombinase complex assembly and function during the early stages of coagulation with additional cofactor activation accomplished by factor Xa. PMID- 2211617 TI - Binding of dolastatin 10 to tubulin at a distinct site for peptide antimitotic agents near the exchangeable nucleotide and vinca alkaloid sites. AB - Dolastatin 10, a potent antimitotic peptide from a marine animal, strongly inhibits microtubule assembly, tubulin-dependent GTP hydrolysis, and the binding of vinca alkaloids to tubulin. In studies of the binding of [3H]vincristine to the protein, with vinblastine as a control for competitive inhibition (Ki, 6.6 microM), we found that the macrolide antimitotic agents maytansine and rhizoxin were also competitive inhibitors (Ki values, 3.1 and 12 microM). Dolastatin 10 and an unrelated peptide antimitotic, phomopsin A, were more potent but noncompetitive inhibitors (Ki values, 1.4 and 2.8 microM). Since maytansine and, to a much lesser extent, vinblastine interfere with nucleotide exchange on tubulin, all drugs were examined for effects on nucleotide interactions at the exchangeable GTP site. Rhizoxin had effects intermediate between those of vinblastine and maytansine. Both peptides inhibited binding of radiolabeled GTP to tubulin even more strongly than did maytansine, but no drug displaced nucleotide from tubulin. The drugs were evaluated for stabilizing effects on the colchicine binding activity of tubulin. The peptides prevented loss of this activity, and vinblastine provided partial protection, while rhizoxin and maytansine did not stabilize tubulin. A tripeptide segment of dolastatin 10 also effectively inhibits tubulin polymerization and GTP hydrolysis. The tripeptide did not significantly inhibit either vincristine binding or nucleotide exchange, nor did it stabilize colchicine binding. These findings are rationalized in terms of a model with two distinct drug binding sites in close physical proximity to each other and to the exchangeable GTP site on beta-tubulin. PMID- 2211618 TI - Sequence analysis of acetylation and methylation in two histone H3 variants of alfalfa. AB - Analysis of acetylation in the two histone H3 variants of alfalfa by acid/urea/Triton-polyacrylamide gel electrophoresis has established that the minor variant H3.2 has a 2-fold higher level of acetylation than the major variant H3.1. Purification and sequence analysis of both variants showed sequence identity across the complete amino-terminal domain, which contains the 6 modified lysines 4, 8, 14, 18, 23, and 27. The two proteins have different distributions for acetylation: mono-, di-, and tri-methylation. The higher level of acetylation of H3.2 was confirmed in a wider pattern across all 6 lysines. Lysine modification levels varied for all sites in both proteins between 5 and 95%, with combinations of one to four types of modification co-existing at each residue. Additional sequence analysis of the H3.1 and H3.2 proteins and of tryptic core peptides established that the two histones differ only in residues 31, 41, 87, and 90. This indicates that major histone H3.1 is the product of the major alfalfa histone H3 gene and makes it likely that H3.2 is the product of the minor H3 gene, known from a partial cDNA clone. The variant-specific differences in lysine modifications in protein domains with identical primary structures suggest that the pattern and level of lysine modifications may be directed by the distinct chromatin environments of the two histone H3 variants. PMID- 2211619 TI - Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A. AB - (R)-Trichostatin A (TSA) is a Streptomyces product which causes the induction of Friend cell differentiation and specific inhibition of the cell cycle of normal rat fibroblasts in the G1 and G2 phases at the very low concentrations. We found that TSA caused an accumulation of acetylated histone species in a variety of mammalian cell lines. Pulse-labeling experiments indicated that TSA markedly prolonged the in vivo half-life of the labile acetyl groups on histones in mouse mammary gland tumor cells, FM3A. The partially purified histone deacetylase from wild-type FM3A cells was effectively inhibited by TSA in a noncompetitive manner with Ki = 3.4 nM. A newly isolated mutant cell line of FM3A resistant to TSA did not show the accumulation of the acetylated histones in the presence of a higher concentration of TSA. The histone deacetylase preparation from the mutant showed decreased sensitivity to TSA (Ki = 31 nM, noncompetitive). These results clearly indicate that TSA is a potent and specific inhibitor of the histone deacetylase and that the in vivo effect of TSA on cell proliferation and differentiation can be attributed to the inhibition of the enzyme. PMID- 2211620 TI - Overlapping Pit-1 and Sp1 binding sites are both essential to full rat growth hormone gene promoter activity despite mutually exclusive Pit-1 and Sp1 binding. AB - A DNA-binding factor present in a wide variety of cell types is shown to bind to a site (GHF2) within the rat growth hormone gene promoter between nucleotides 147 and -129. Biochemical and transcriptional properties identify this factor as Sp1. The degree of glycosylation of one of the forms of Sp1 is observed to vary in a cell type-specific fashion. The GHF2 binding site overlaps with the more distal (dGHF1) of the two binding sites for the pituitary-specific transcription factor Pit-1. DNase I footprinting and gel retardation analysis with partially purified Sp1 and Pit-1 show that Sp1 and Pit-1 binding to these sites is mutually exclusive. Despite the inability of these two transcription factors to be simultaneously bound to their overlapping sites in vitro, the structural integrity of both binding sites appears essential to the maximal expression of the rat growth hormone promoter after transfection into pituitary GC cells. These findings suggest that activation of the rat growth hormone promoter by Sp1 and Pit-1 may occur through a multistage mechanism. PMID- 2211621 TI - Multiple mutations of the human cytochrome P450IID6 gene (CYP2D6) in poor metabolizers of debrisoquine. Study of the functional significance of individual mutations by expression of chimeric genes. AB - The debrisoquine/sparteine-type polymorphism is a clinically important inherited variation of drug metabolism characterized by two phenotypes, the extensive metabolizer and the poor metabolizer (PM). Five to 10 percent of individuals in Caucasian populations are of the PM phenotype and have deficient metabolism of debrisoquine and over 25 other drugs. Our previous studies have revealed absence of cytochrome P450IID6 protein and aberrant splicing of IID6 premRNA in livers of PMs. Moreover, two mutant alleles of the P450IID6 gene locus (CYP2D6) were identified by restriction fragment length analysis to be associated with the PM phenotype. However, the mutations of the CYP2D6 gene causing absent P450IID6 protein have not been defined. Here we report the cloning and sequencing of two types of mutant alleles of CYP2D6 isolated from genomic libraries of three PM individuals. One allele (29-A) was characterized by a single nucleotide deletion in the 5th exon with consequent frameshift and was observed in one individual only. The other type of mutant allele (29-B) was present in all three PM individuals and its sequence contained multiple mutations, notably four base changes causing amino acid changes in exons 1, 2 and 9, and a point mutation at the consensus sequence of the splice site of the 3rd intron. To understand the significance of the individual mutations, chimeric genes were constructed between the wild-type IID6 gene and the mutant 29-B allele or site-specific mutations were introduced into the IID6-cDNA and these DNA constructs were transiently expressed in COS-1 cells. The mutations in exon 1 resulted in a functionally deficient IID6 protein and the mutation at the splice site in absent IID6 protein, whereas the mutations in exons 2 and 9 were of no consequence for IID6 function. Only the mutation at the splice site thus explains the absence of P450IID6 protein in livers of PM individuals and appears to be a common cause of polymorphic drug oxidation. PMID- 2211622 TI - Characterization of Escherichia coli cells deficient in 1-acyl-sn-glycerol-3- phosphate acyltransferase activity. AB - A mutant of Escherichia coli K-12 defective in 1-acyl-sn-glycerol-3-phosphate acyltransferase has been isolated. At the permissive temperature for growth, 30 degrees C, 20% of the total cellular glycerophospholipids is 1-acyl-sn-glycerol-3 phosphate, as identified by mass spectral analysis and proton NMR. This percentage of 1-acyl-sn-glycerol-3-phosphate rises to about 30% when the temperature of the culture is shifted to 42 degrees C. This increase is primarily at the expense of phosphatidylethanolamine. Extracts from cells harboring the plsC mutation have no detectable 1-acyl-sn-glycerol-3-phosphate acyltransferase activity. The fatty acid composition of the accumulated 1-acyl-sn-glycerol-3 phosphate is about 60% cis-vaccenate and 40% palmitate, with no detectable amounts of palmitoleate or other fatty acids, consistent with the known fatty acid composition of the sn-1 position of glycerophospholipids. The isolation of this gene, plsC, completes the list of genes known to be required for the synthesis of the major glycerophospholipids in E. coli. PMID- 2211624 TI - Secretion of killer toxin encoded on the linear DNA plasmid pGKL1 from Saccharomyces cerevisiae. AB - By the kar1-mediated cytoduction, linear double-stranded DNA plasmids pGKL1 and pGKL2, encoding killer toxin complex, have been successfully transferred to the recipient strains with about 30% frequency. The killer toxin was found to be secreted through the normal yeast secretory pathway by introducing pGKL plasmids into the several Saccharomyces cerevisiae sec mutants and examining the secretion of killer toxin. S. cerevisiae cells, harboring newly isolated deletion plasmid pGKL1D, expressed only the 28K protein among three killer subunits, and secreted the 28K subunit at a level of zero to 20% efficiency of the cells containing intact pGKL1 plasmid. These data indicated that subunit interaction (cosecretion) of killer proteins is required for the efficient secretion of 28K subunit. The 28K precursor protein was found to translocate across the canine pancreatic endoplasmic reticulum membrane under the direction of its own signal peptide in vitro without any other subunits. From kex2 mutant cells harboring pGKL1 plasmid, the 97K subunit, and its precursor 128K protein were not secreted, however, the 28K subunit was secreted in the same amount as that secreted from KEX2 cells. These lines of evidence suggest that the final assembly of killer toxin complex after KEX2 site of Golgi apparatus is not essential for the secretion of 28K subunit, and therefore, that putative interaction between 128K protein and 28K subunit for the transport between endoplasmic reticulum and Golgi apparatus may be required for the efficient secretion of 28K subunit. PMID- 2211623 TI - Effects of amino acid replacements within the tetrabasic cleavage site on the processing of the human insulin receptor precursor expressed in Chinese hamster ovary cells. AB - We have studied the specificity requirements for processing of the human insulin proreceptor by successively replacing each basic amino acid in the tetrabasic cleavage site with alanine. These mutated receptor cDNAs have then been overexpressed in Chinese hamster ovary cells, using vectors containing the mouse dihydrofolate reductase gene to amplify the transfected cDNAs in the presence of increasing concentrations of methotrexate. High levels of expression, ranging up to 6 x 10(7) receptors/cell were achieved in these experiments. Replacement of the P1 arginine with alanine led to the complete suppression of processing, as occurs also in a naturally occurring serine mutation at this site (Yoshimasa, Y., Seino, S., Whittaker, J., Kakehi, T., Kosaki, A., Kuzuya, H., Imura, H., Bell, G. I., and Steiner, D. F. (1988) Science 240, 783-787). A small amount of cleavage at alternative sites was detected. Replacement of the P2 arginine or P3 lysine with alanine did not in either case affect conversion to mature alpha and beta subunits, while replacement of the P4 arginine significantly inhibited processing. The binding isotherms for the processed versions of the receptor were comparable to previously published normal values. The unprocessed proreceptor bound insulin normally but was autophosphorylated less efficiently than processed versions of the receptor expressed in the same cells. These results suggest that a single processing protease with trypsin-like specificity may be involved in processing both insulin and insulin-like growth factor-I receptor precursors as well as a variety of viral envelope glycoprotein precursors. PMID- 2211625 TI - Interaction of osteogenin, a heparin binding bone morphogenetic protein, with type IV collagen. AB - Osteogenin, an extracellular matrix component of bone, is a heparin binding differentiation factor that initiates endochondral bone formation in rats when implanted subcutaneously with an insoluble collagenous matrix. We have examined the interaction of osteogenin with various extracellular matrix components including basement membranes. Osteogenin, purified from bovine bone, binds avidly to type IV collagen and to a lesser extent to both type I and IX collagens. Osteogenin binds equally well to both native and denatured type IV collagen. Both alpha 1 and alpha 2 chains of type IV collagen are recognized by osteogenin. Osteogenin binds to a collagen IV affinity column, and is eluted by 6.0 M urea with 1 M NaCl, pH 7.4, and the eluate contained the osteogenic activity as demonstrated in vivo. Binding of osteogenin to collagen IV is not influenced by either laminin or fibronectin. These results imply that osteogenin binding to extracellular matrix components including collagens I and IV and heparin may have physiological relevance, and such interactions may modulate its local action. PMID- 2211626 TI - Flanking AT-rich tracts cause a structural distortion in Z-DNA in plasmids. AB - The effect of neighboring AT-rich sequences on the right-handed B to left-handed Z transition was investigated in plasmids. The supercoil stabilized Z-DNA structure in (CG) tracts 36 and 40 base pairs (bp) in length revealed an unexpected conformational aberration at defined C residues proximal to one end (colL) when the inserts were bilaterally flanked by an 80% AT-rich segment (90 bp on one side and 331 bp on the other). The presence of the perturbed Z conformation required (CG) stretches longer than 32 bp and bilateral flanking by the AT-rich tracts, since plasmids with the (CG) tracts unilaterally flanked had an orthodox Z-structure. The thermodynamics of the negative super-coil-induced transitions were influenced only slightly by the neighboring AT-rich regions. Hence, the nature of Z-conformations in plasmids is markedly influenced by intrinsic structural features of the (Pur-Pyr) tract and by seemingly modest changes in the properties of neighboring sequences over a distance of several helical turns. PMID- 2211627 TI - Translocation of ProOmpA possessing an intramolecular disulfide bridge into membrane vesicles of Escherichia coli. Effect of membrane energization. AB - In the absence of delta mu H+, the in vitro translocation of proOmpA resulted in the stable accumulation of a possible translocation intermediate in addition to a transiently accumulating one. The stable intermediate was detected on a polyacrylamide gel as two proteinase K-resistant bands corresponding to a molecular weight of about 28,000. The appearance of the bands was appreciably enhanced when proOmpA was oxidized with ferricyanide. No mature OmpA appeared. When proOmpA reduced with dithiothreitol was used, on the other hand, the bands did not appear at all. Upon the replacement of Cys302 of OmpA with Gly, the intermediate accumulation was abolished. The proOmpA treated with dithiothreitol was labeled with N-[3H]-ethylmaleimide, whereas that treated with ferricyanide was not. The ferricyanide-treated proOmpA was translocated into membrane vesicles in the presence of delta mu H+. The mature OmpA thus translocated and processed was not labeled with N-[3H]ethylmaleimide. It is concluded that proOmpA possessing the Cys290-Cys302 disulfide bridge can be translocated without cleavage of the bridge, when delta mu H+ is imposed. The accumulation of the disulfide bridge-containing intermediate was ATP-dependent, whereas its conversion to the translocated mature form was not blocked in the presence of adenosine 5'-(beta, gamma-imino)triphosphate. It is concluded that the early and late stages of the translocation reaction require ATP and delta mu H+ differently. PMID- 2211628 TI - Characterization of an active single polypeptide form of the human immunodeficiency virus type 1 protease. AB - The pepsin-like aspartyl proteases consist of a single polypeptide chain with topologically similar amino- and carboxyl-terminal domains, each of which contributes 1 aspartic acid residue to the active site. This structure has been proposed to have evolved by gene duplication and fusion from a dimeric enzyme composed of two identical polypeptide chains, such as the aspartyl protease (PRT) of human immunodeficiency virus type 1 (HIV-1). To determine if a single polypeptide form of the HIV-1 protease would be enzymatically active, two protease coding regions were linked to form a dimeric gene (pFGGP). Expression of this gene in Escherichia coli yielded a protein with the expected molecular mass of 22 kDa. The in vitro kinetic parameters of PRT and FGGP (where FGGP is the single polypeptide form of the HIV-1 protease with 2 glycine residues connecting the two subunits) for three peptide substrates are similar. Construction and analysis of a CheY-GAG-FGGP fusion protein demonstrated that FGGP is capable of precursor processing in vivo. Mutation of one or both of the active site aspartates to either asparagine or glutamate rendered the enzyme inactive, demonstrating that both active site aspartate residues are required for enzymatic activity. PMID- 2211629 TI - Differential effects of brefeldin A on sialylation of N- and O-linked oligosaccharides in low density lipoprotein receptor and epidermal growth factor receptor. AB - Low density lipoprotein receptor (LDL-R) is a membrane glycoprotein carrying both N- and O-linked oligosaccharides, processing of which is reflected in conversion from a precursor to mature form during its synthesis and intracellular transport. Treatment with brefeldin A (BFA) of mouse macrophage-like J774 cells, Chinese hamster ovary cells, and two human cancer cell lines (A431 and IMC-2) resulted in production of LDL-R with a molecular size 5-10 kDa smaller than that of the mature form in the control cells. Treatment with sialidase caused apparent reduction in the molecular size of LDL-R synthesized in all BFA-treated J774, Chinese hamster ovary, A431, and IMC-2 cell lines as observed for the mature form of the control cells. Thus, O-linked sugar chains of LDL-R were apparently sialylated in the BFA-treated cells. We also examined the effect of BFA on the processing of another membranous glycoprotein, epidermal growth factor receptor (EGF-R) carrying only N-linked oligosaccharides. EGF-R synthesized in the presence of BFA was found to have no response to sialidase treatment, suggesting that the drug blocks the sialylation of EGF-R. The results indicate that BFA causes different effects on the sialylation of LDL-R and EGF-R depending upon linkage types of their oligosaccharides. PMID- 2211630 TI - Multiple preproenkephalin transcriptional start sites are induced by stress and cholinergic pathways. AB - A major control of gene expression occurs at the level of initiation of RNA transcription. In the nervous system this is reflected in part by 5' end RNA heterogeneity of neural transcripts. We now report the characterization of four preproenkephalin (ppEnk) RNA initiation sites in the rat brain striatum. In the adrenal medulla two ppEnk transcriptional start sites were detected. Moreover, cholinergic induction of ppEnk RNA initiation was observed in the adrenal medulla, but not in the striatum. The converse was true following handling stress. Our observations suggest that selective start site usage and stimulus evoked induction of specific RNA initiation is tissue-specific. We speculate that start site usage and induction may provide separate mechanisms through which neuronal gene expression is controlled in anatomically, as well as functionally distinct neurohumoral structures. PMID- 2211631 TI - An intragenic region downstream from the dihydrofolate reductase promoter is required for replication-dependent expression. AB - The gene encoding dihydrofolate reductase (DHFR) is down-regulated as myoblasts withdraw from the cell cycle and commit to terminal differentiation. To localize cis-acting elements involved in regulating DHFR gene expression, the DHFR promoter and upstream region, together with differing amounts of contiguous intragenic sequence, were fused to the bacterial chloramphenicol acetyltransferase (CAT) gene. The resulting fusion genes were stably transformed into muscle cells, and CAT mRNA levels were measured in proliferative myoblasts and committed myocytes. A gene consisting of the -850/+465 region of DHFR (numbers refer to distance in base pairs from transcription initiation site) fused to CAT was efficiently expressed in proliferating myoblasts and was appropriately down-regulated during commitment. A gene consisting of the -850/+60 region of DHFR fused to CAT was poorly expressed in proliferating myoblasts and was not down-regulated during commitment. When inserted between the Rous sarcoma virus promoter and CAT sequence of RSVpCAT, the +61/+465 region of the DHFR gene augmented CAT mRNA expression in muscle cell transformants but did not confer a regulated pattern of expression. Our data indicate that DHFR sequences between +60 and +465 are required but are not sufficient for replication-dependent expression. The DHFR sequences may be operating at either a transcriptional or posttranscriptional level. PMID- 2211633 TI - Preliminary crystallographic data for the thiamin diphosphate-dependent enzyme pyruvate decarboxylase from brewers' yeast. AB - Single crystals of the thiamin diphosphate (the vitamin B1 coenzyme)-dependent enzyme pyruvate decarboxylase (EC 4.1.1.1) from brewers' yeast have been grown using polyethylene glycol as a precipitating agent. Crystals of the homotetrameric version alpha 4 of the holoenzyme are triclinic, space group P1, with cell constants a = 81.0, b = 82.4, c = 116.6 A, alpha = 69.5 beta = 72.6, gamma = 62.4 degrees. The crystals are reasonably stable in a rotating anode x ray beam and diffract to at least 2.5 A resolution. The Vm value of 2.55 A/dalton is consistent with a unit cell containing four subunits with mass of approximately 60 kDa each. Rotation function results with native data indicate strong non-crystallographic 222 symmetry relating the four identical subunits, thus density averaging methods are likely to play a role in the structure determination. PMID- 2211632 TI - Transcriptional activator LEU3 of yeast. Mapping of the transcriptional activation function and significance of activation domain tryptophans. AB - The LEU3 protein of yeast activates a number of genes in the branched chained amino acid pathways. Native LEU3 is modulated by alpha-isopropylmalate, an intermediate in leucine biosynthesis. alpha-Isopropylmalate is needed for transcriptional activation, but not for DNA binding. We show here that the transcriptional activation function of LEU3 resides within the C-terminal 32 amino acids. An adjacent stretch of 81 residues is dispensable and apparently forms a connecting link between the activation domain and a large central region previously identified as important for modulation. The newly defined activation domain contains a cluster of three tryptophan residues, each of which was changed to alanine by site-directed mutagenesis. Surprisingly, all three Trp----Ala mutations affect modulation. One of them, Trp-864----Ala, creates a LEU3 molecule that is largely unmodulated and also is a better transcriptional activator than is wild type LEU3 ("hyperactivator"). The other two mutations (Trp-861----Ala and Trp-870----Ala) change the modulation ratio but have no effect on the maximal activation efficiency of the activator. We propose that the activation domain of LEU3 is kept silent by association with the central region of the protein and that an alpha-isopropylmalate-induced conformational change in the central region releases and thus activates the activation domain. PMID- 2211634 TI - Identification of sorbitol 3-phosphate and fructose 3-phosphate in normal and diabetic human erythrocytes. AB - Using 31P NMR spectroscopy, we have identified sorbitol 3-phosphate and fructose 3-phosphate in normal human erythrocytes wherein their concentrations are estimated to be 13 mumol/liter cells. Incubation of hemolysates with sorbitol, fructose and ATP suggest that both sorbitol and fructose are phosphorylated separately and directly at the 3-hydroxyl position suggesting the presence in these cells of a novel and specific kinase(s). In addition to sorbitol 3 phosphate and fructose 3-phosphate which were previously identified in the mammalian lens and sciatic nerve, erythrocytes have two extra metabolites resonating at 6.7 and 6.8 ppm in the 31P NMR spectrum. Although not identified in this study, the unusual chemical shifts of these compounds, their low pKa values and the fact that they appear as doublet in proton-coupled 31P NMR spectra, suggest that these phosphomonoesters belong to the same class of metabolites as sorbitol 3-phosphate and fructose 3-phosphate. Preliminary studies of erythrocytes from an unselected group of diabetic subjects showed an overall increase in the concentration of all four metabolites, although an overlap with normal values was noted. PMID- 2211635 TI - Endothelin, a potent peptide agonist in the liver. AB - Endothelin, a peptide mediator produced by vascular endothelial cells, caused sustained vasoconstriction of the portal vasculature in the perfused rat liver. The vasoactive effect of endothelin was accompanied by increased glycogenolysis and alterations in hepatic oxygen consumption. The endothelin-induced increase in the portal pressure was concentration-dependent with an EC50 of 1 nM. Endothelin induced hepatic glycogenolysis was dose-dependent but exhibited a different EC50 than for the vasoconstrictive effects of endothelin. Hepatic vasoconstriction and glycogenolysis following endothelin infusion were inhibited when Ca2+ was removed from the perfusion medium. The endothelin-induced responses in the liver were not altered by prior infusion of phenylephrine (alpha-adrenergic agonist), isoproterenol (beta-adrenergic agonist), angiotensin II, glucagon, platelet activating factor, or the platelet-activating factor antagonist, BN52021. However, repeated infusion of endothelin resulted in desensitization of the glycogenolytic response but was without a significant effect on hepatic vasoconstriction. Endothelin also stimulated metabolism of inositol phospholipids in isolated hepatocytes and Kupffer cells in primary culture. The present experiments demonstrate, for the first time, that endothelin is a very potent agonist in the liver eliciting both a sustained vasoconstriction of the hepatic vasculature and a significant increase in hepatic glucose output. PMID- 2211636 TI - Multiple roles of divalent cation in the terminal deoxynucleotidyltransferase reaction. AB - Terminal deoxynucleotidyltransferase activity is absolutely dependent on the presence of a divalent cation in the reaction mixture. This requirement can be satisfied by either Mg2+, Co2+, or Mn2+. When Mg2+ is used, the reaction rate is inhibited by metal ligands, and this inhibition can be reversed by Zn2+. Reaction rates in Mg2+ are also stimulated by the addition of micromolar amounts of Zn2+. To examine the role of Zn2+ in terminal transferase catalysis we analyzed for Zn2+ in homogeneous recombinant human terminal transferase preparations and found that Zn2+ is not an intrinsic part of enzyme molecule. Analysis of Zn2+ binding to terminal transferase under equilibrium conditions shows about 0.3 g of atom of Zn2+/mol of enzyme, suggesting that Zn2+ forms an easily dissociable complex with the enzyme molecule. Kinetic analyses showed that the stimulatory effect of Zn2+ is observed in several buffer systems. Zn2+ increases the affinity of the enzyme for the initiator about 2-fold and decreases affinity for dATP more than 10-fold, resulting in an increase in the apparent Vmax of the reaction. Using a 3'-ended 2',3'-dideoxyoligonucleotide as an inhibitor demonstrates that the inhibitor has no effect on the reaction rate in the absence of Zn2+ but is competitive with respect to the initiator in the presence of Zn2+. These results suggest that Zn2+ is a positive effector for terminal transferase, interacting with oligonucleotide and enzyme near the initiator binding site. Binding of Zn2+ to the enzyme appears to induce conformational changes that greatly increase the Vmax of the reaction with a concomitant decrease in the affinity of the enzyme for dNTP. PMID- 2211637 TI - Recognition of the tRNA-like structure in tobacco mosaic viral RNA by ATP/CTP:tRNA nucleotidyltransferases from Escherichia coli and Saccharomyces cerevisiae. AB - The 3'-terminal tRNA-like structure of the tobacco mosaic virus RNA interacts with ATP/CTP:tRNA nucleotidyltransferases from Escherichia coli or yeast in much the same manner as do tRNAs. Primary sites of interaction cluster near the 3' end and in the loop proposed to be analogous to the psi-loop of a tRNA. Some modified bases in the tRNA-like structure inhibit interaction with nucleotidyltransferase, yet the analogous bases in a tRNA do not. The location of some of these nucleotides within the analog to the psi-loop suggests that this structure differs slightly from its counterpart in a tRNA. The location of other such bases in the helical stem near the 3' end can be explained if the pseudoknot is disrupted by these modified bases or if the tertiary structure of the RNA is altered in the enzyme-RNA complex. A partially denatured secondary structure that persists on denaturing gels is proposed. PMID- 2211638 TI - Resonance-enhanced Raman scattering from the molybdenum center of xanthine oxidase. AB - The molybdenum center of xanthine oxidase has been examined by resonance Raman spectroscopy. Making use of the long-wavelength absorption of the reduced molybdenum center in complex with violapterin (the product of enzymic action of lumazine), resonance Raman spectra were obtained using laser excitation at 676.4 nm. Several internal vibrational modes of violapterin were found to be resonance enhanced, and a number of bands in the 250-1100 cm-1 range, presumably arising from vibrational modes of the molybdenum coordination sphere, were also observed. Upon substitution of 18O for 16O in the molybdenum coordination sphere, bands at 1469, 853, 517, 325, and 276 cm-1 exhibited shifts of 5-12 cm-1 to lower energy. By analogy to previous vibrational studies of Mo-O-Mo and Mo-O-R model compounds, the 853, 517, and 276 cm-1 frequencies were judged consistent with a labeled Mo-O R linkage of the complexed violapterin. More importantly, the relatively small frequency shifts observed in these and other vibrations upon incorporation of 18O are very similar to those observed by others for 18O-labeled phenol and metal phenolate complexes (Pinchas, S., Sadeh, D., and Samuel, D. (1965) J. Phys. Chem. 69, 2259-2264; Pyrz, W. J., Rue, L. A., Stern, L. J., and Que, L. J., Jr. (1985) J. Am. Chem. Soc. 107, 614-620) that model iron-tyrosinate proteins. The relatively small isotope-induced frequency shifts in multiple bands are thus interpreted as resulting from vibrational mixing of internal coordinates involving the oxygen atom with internal ring motions of the aromatic species. No oxygen isotope-sensitive bands were observed in the 900-1100 cm-1 region where Mo = O stretching modes typically occur. In agreement with the conclusions of previous workers (Davis, M.D., Olson, J. S., and Palmer, G. (1982) J. Biol. Chem. 257, 14730-14737) we interpret our results to indicate that the absorption band appearing upon complexation of violapterin with the molybdenum center of reduced xanthine oxidase is a molybdenum-to-violapterin charge-transfer band. These results, as well as several other lines of evidence, are consistent with direct coordination of violapterin to molybdenum in the charge-transfer complex via the 7-hydroxyl group (i.e. the hydroxyl group introduced into substrate by the enzyme). The Mo=O stretching mode of the complex is presumably not resonance enhanced because it is orthogonal to the charge-transfer electronic transition, suggesting that coordination of violapterin is cis to the oxo group.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2211639 TI - Molecular cloning of wheat dihydrodipicolinate synthase. AB - Four forms of dihydrodipicolinate synthase (DHDPS), which catalyzes the first reaction in the lysine-specific biosynthetic pathway in higher plants, were purified to homogeneity from a suspension culture of wheat (Triticum aestivum). These polypeptides have similar N-terminal amino acid sequences. Two different cDNA clones were isolated by screening a wheat cDNA library with oligonucleotide probes based on these amino acid sequences. The predicted amino acid sequences indicate that both clones encode putative chloroplast transit peptides that have little homology to each other as well as the conserved mature protein portions of Mr 35,737 and 35,776 (94% identity). Mature wheat DHDPS has 30% amino acid identity to Escherichia coli DHDPS. One of the cloned cDNAs, which had been fused to bacterial transcription/translation signals, genetically complemented a strain of E. coli that lacks endogenous DHDPS activity. Moreover, the expression of wheat DHDPS cDNA in wild-type E. coli increased the enzymatic activity 10-fold in the transformed bacteria. PMID- 2211640 TI - cDNA sequence, in vitro synthesis, and intramitochondrial lipoylation of H protein of the glycine cleavage system. AB - H-protein is a component of the glycine cleavage system loosely associated with the mitochondrial inner membrane and has lipoic acid as a prosthetic group. cDNA clones encoding H-protein were isolated from a bovine liver cDNA library with an oligonucleotide probe from the amino acid sequence of the NH2-terminal region. DNA sequence analysis and deduced amino acid sequence showed that the cDNAs encoded an H-protein precursor of 173 amino acids including a 48-amino acid presequence. Calculated molecular mass of the precursor and mature protein without lipoic acid were 18,790 and 13,846, respectively. Northern blot analysis indicated a major mRNA component of 1.1 kilobases and a minor component of 0.6 kilobase. The result is consistent with the presence of two adenylation signals in the 3'-untranslated region of the cDNA. In vitro transcription and translation of the H-protein cDNA produced a 19-kDa protein recognized by antibody raised to chicken H-protein. Bovine liver H-protein precursor has no lipoic acid prosthetic group. When incubated with isolated bovine liver mitochondria, the precursor was imported into mitochondria, processed to its mature form with a molecular mass of 14 kDa, and lipoylated at lysine 59. These results indicate that lipoylation is not required for the import of H-protein precursor into mitochondria and H protein is lipoylated in mitochondria which probably contain the physiologically active form of lipoic acid as well as the enzyme(s) responsible for the attachment. PMID- 2211641 TI - Sodium butyrate selectively alters thyroid hormone receptor gene expression in GH3 cells. AB - High-affinity binding of thyroid hormone (T3) to nuclear receptors influences the transcriptional rate of specific genes. The carboxylic acid, sodium butyrate, is known to reduce nuclear binding of T3 in GH3 rat pituitary cels, and this effect correlates with inhibition of T3 responsiveness. Incubation of GH3 cells with 10 mM, but not 1 mM, sodium butyrate abolishes induction of growth hormone gene expression by T3. The relationship between thyroid hormone receptor (TR) depletion and inhibition of T3 action was further investigated by determining the effects of sodium butyrate on TR gene expression. GH3 cells contain mRNAs encoding at least three thyroid hormone receptors (TRs alpha 1, beta 1, and beta 2), as well as a related non-T3 binding repressor or T3 action (c-erbA alpha 2). Remarkably, 10 mM sodium butyrate reduces TR beta 2 mRNA levels by greater than 95% in the presence or absence of T3. The down-regulation of TR beta 2 mRNA occurs at a concentration of sodium butyrate between 5 and 10 mM and is maximal by 8 h of treatment. In contrast, TR beta 1 mRNA levels are unchanged. Furthermore, sodium butyrate has little effect on the mRNAs encoding TR alpha 1 and c-erbA alpha 2. Nuclear run-on assays indicated that sodium butyrate depletes TR beta 2 mRNA by rapidly repressing TR beta 2 gene transcription. In the presence of the transcriptional inhibitor, actinomycin D, the half-life of TR beta 2 mRNA was approximately 3 h in the presence or absence of sodium butyrate. Thus, the reduction in TR number induced by sodium butyrate is likely to be due to the transcriptionally mediated reduction in TR beta 2 mRNA. These data suggest that TR beta 2 has an important physiological role in the regulation of growth hormone gene expression by T3. PMID- 2211642 TI - Construction and properties of active chimeric enzymes between human aldolases A and B. Analysis of molecular regions which determine isozyme-specific functions. AB - To study the structure/function relationships of human aldolase isozymes, particularly isozyme-specific functions, we constructed Escherichia coli expression plasmids for six BA chimeric enzymes (BA34, BA108, BA137, BA212, BA306, and BA306*), each composed of the N-terminal side of isozyme B and the C terminal side of isozyme A, and one BAB chimeric enzyme which contains a fragment of isozyme A (residues 213-306) inserted in between the N-terminal and the C terminal fragments of isozyme B. They were transfected into E. coli, and the generated enzymes were characterized. This study reveals the following. (i) For isozyme A, the C-terminal Tyr-363 and the N-terminal region bearing isozyme group specific sequences 1-3 and Lys-107 (the C-6 phosphate-binding site) are responsible for the higher catalytic activity toward fructose 1,6-bisphosphate, which is 7 times higher than that of aldolase B. Conversely, an internal region spanning positions 108-212 is required for the lower activity toward fructose 1 phosphate. (ii) For isozyme B, an internal sequence spanning positions 108-212 which includes some isozyme B-specific residues and a postulated C-1 phosphate binding site (Lys-146 or Arg-148) is responsible for a higher catalytic activity toward fructose 1-phosphate, which is 8-10 times that of isozyme A. The more upstream sequence containing positions 1-107 is responsible for the lower catalytic activity toward fructose 1,6-bisphosphate. (iii) At least residues 212 306, composing a long stretch near the active-site Lys-229 and highly conserved among isozymes A, B, and C, may be required for the basal framework of the aldolase molecule to exhibit the activity common to the three isozymic forms. PMID- 2211643 TI - Purification and characterization of a 19-kilodalton intracellular protein. An activation-regulated putative protein kinase C substrate of T lymphocytes. AB - Activation of protein kinase C in T cells results in rapid phosphorylation of a 19-kDa intracellular protein termed 19K. We report the purification of 19K from human peripheral T cells and an internal 20-amino acid sequence determined from this protein. It is shown that 19K is a novel cytoplasmatic protein which is phosphorylated in vitro by partially purified protein kinase C. 19K-specific antibodies, raised by immunizing rabbits with purified protein, were used to show that the 19K is expressed, and phosphorylated in response to protein kinase C activation, in several cellular systems. These antibodies were also used to precipitate 19K from both [35S]methionine and 32Pi-labeled T cells. The data showed that 15 min of phorbol ester treatment has no effect on the rate of 19K synthesis but results in induction of 19K phosphorylation. However, we demonstrate, by Western blot analysis, that expression of 19K in primary peripheral T cells increased at least 10-fold over a period of 4 days after activation. The increase in 19K expression correlates with initiation of DNA synthesis, and in proliferating T cells 19K comprises approximately 0.2% of total cytoplasmatic protein. Thus, 19K is a novel putative protein kinase C substrate which is subject to activation associated up-regulation in human T cells. PMID- 2211644 TI - Plasma cell membrane glycoprotein PC-1. cDNA cloning of the human molecule, amino acid sequence, and chromosomal location. AB - The murine cell membrane glycoprotein PC-1 is a homodimer with restricted tissue distribution, being first characterized in plasma cells. We now describe the isolation of cDNA clones encoding the human homolog of the murine PC-1 protein, its complete amino acid sequence, and its chromosomal location. Overall, the amino acid sequence of the human protein is about 80% identical to the murine protein, although the extent of homology varies in different domains. It had not been possible to assign a definitive amino terminus to the murine protein. Comparison of the murine and human sequence necessitates reassignment of the amino terminus, resulting in a cytoplasmic tail of 24 amino acids rather than 58 amino acids as previously published for the mouse. The sequence of several independently obtained cDNA clones indicates that the 3' end of the mRNA is subject to alternative splicing. Southern blots suggest a single copy gene. In situ chromosomal hybridization localizes the gene for human PC-1 to chromosome 6q22-q23, a common site for deletions in human lymphoid neoplasia. PMID- 2211645 TI - A neutral phospholipase D activity from rat brain synaptic plasma membranes. Identification and partial characterization. AB - Rapid activation of phospholipase D (PLD) in response to cell stimulation was recently demonstrated in many systems, raising the hypothesis that PLD participates in transduction of extracellular signals across the plasma membrane. In the present study, we describe the identification of a neutral PLD activity in purified rat brain synaptic plasma membranes, and the in vitro conditions required to assay its catalytic activity with exogenous [3H]phosphatidylcholine as substrate. Production of [3H]phosphatidic acid, the natural lipid product of PLD and of [3H]phosphatidylethanol, catalyzed by PLD in the presence of ethanol via transphosphatidylation, were measured. The synaptic membrane PLD exhibited its highest activity at pH 7.2 and was thus defined as a neutral PLD. Enzyme activity was absolutely dependent on the presence of sodium oleate and was strongly activated by Mg2+ ions (at 1 mM). Ca2+ at concentrations up to 0.25 mM was as stimulatory as Mg2+, but at 2 mM it completely inhibited enzyme activity. Mg2+ extended the linear phase of PLD activity from 2 to 15 min, suggesting that it may stabilize the enzyme under our assay conditions. The production of [3H]phosphatidylethanol was a saturable function of ethanol concentration. Production of [3H] phosphatidic acid was inversely related to the concentration of ethanol and to the accumulation of phosphatidylethanol, indicating that the two phospholipids are indeed produced by the competing hydrolase and transferase activities of the same enzyme. beta,beta-Dimethylglutaric acid, utilized previously as a buffer in studies of rat brain PLD, inhibited enzyme activity at neutral pH but not at acidic pH. The properties of the neutral synaptic membrane PLD and its relationships with other in vitro, acid, and neutral PLD activities, as well as with the signal-dependent PLD detected in intact cells, are discussed. PMID- 2211646 TI - Oxygen and temperature dependence of stimulated insulin secretion in isolated rat islets of Langerhans. AB - The effects of lowered O2 tension on insulin secretion and changes in cellular energy parameters were investigated in isolated rat pancreatic islets perifused with buffers equilibrated with 21, 9, 5, and 1% oxygen and containing 5 mM glucose. Decreasing the external [O2] reduced the amount of insulin released in response to 16 mM glucose, 20 mM alpha-ketoisocaproic acid, and 40 mM KCl. Secretion elicited by high glucose or KCl had declined significantly at 9% oxygen, whereas that caused by alpha-ketoisocaproic acid became inhibited below 5% O2. Lowering the oxygen tension also decreased the ability of islets to respond with a rise in [ATP]/[ADP] upon stimulation with metabolic secretagogues. This reduction in the evoked increase in the nucleotide ratios paralleled the inhibition of stimulated insulin secretion. Addition of 2 mM amytal markedly decreased the islet energy level and eliminated the secretory response to 16 mM glucose. The results suggest that enhancement of B-cell energy production and a consequent rise in [ATP] (or [ATP]/[ADP]) are a necessary event for the hormone release elicited by high glucose and alpha-ketoisocaproic acid. A decrease in temperature inhibited insulin secretion with all three secretagogues tested. The energies of activation were similar for high glucose and KCl-induced secretion, about 20 kcal/mol, but were higher for alpha-ketoisocaproic acid, about 35 kcal/mol. At 28 degrees C, the [ATP]/[ADP] was larger than that at 38 degrees C (8 versus 5) and was not increased further upon addition of 16 mM glucose. It is suggested that a decrease in the rate of energy production at lowered temperatures may contribute to the inhibition of insulin release caused by metabolic secretagogues. PMID- 2211647 TI - Analysis of the generation and inhibition of factor Xa. Area under generation curves is independent of enzyme generation rate. AB - The activation of factor X in the presence of antithrombin has been studied in order to determine the parameters that control the area under the resulting factor Xa generation curve. Generation curves were analyzed using a model containing three parameters: the total generation of factor Xa, Emax; the rate of factor Xa generation, expressed as a first-order rate constant, kappa 1; and the rate of inhibition, expressed as another first-order rate constant, kappa 2. Using factor IXa-VIIIa to activate factor X, we found the area under the generation curve to be proportional to Emax, which was varied by varying the factor IXa concentration, and inversely proportional to kappa 2, which was varied by varying the antithrombin concentration. With this activator, however, kappa 1 varied in parallel with Emax, resulting in a correlation between integrated area and kappa 1. In order to determine whether Emax or kappa 1, or both, was a controlling parameter, similar activations were done with varying concentrations of the factor X-activating enzyme of Russell's viper venom. With this activator it was possible to vary Emax and kappa 1 independently, again at varying antithrombin concentrations. These results showed the integrated area to be proportional to Emax and inversely proportional to kappa 2, as before, but independent of the activation rate, kappa 1. In this system, therefore, the area under the factor Xa generation curve is controlled by the amount of factor Xa generated and its rate of inhibition but is independent of the rate of factor Xa generation. PMID- 2211648 TI - Sulfate transport by rat liver lysosomes. AB - Sulfate transport was examined using membrane vesicles (pH 7.0 inside) prepared from rat liver lysosomes. Sulfate uptake was dependent upon external pH with increased uptake at lower buffer pH. The Km for uptake was 160 microM at pH 5.0 while at pH 7.0, a lower affinity system with a Km of 1.4 mM was present. The protonophore carbonyl cyanide m-chlorophenylhydrazone increased uptake at pH 5.0 while valinomycin/KCl had no effect. In contrast, at pH 7.0, valinomycin-induced changes in membrane potential stimulated uptake. Countertransport of sulfate at pH 7.0 was inhibited by 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene, N-(4 azido-2-nitrophenyl)-2-aminoethanesulfonic acid, and a variety of anions: SO4(2-) greater than MoO4(2-) greater than Cl- greater than HPO4- greater than HCO3-. Trans-stimulation of sulfate uptake at pH 7.0 was observed with MoO4(2-) and, to a lesser extent, with S2O3(2-) while Cl-, HPO4-, and HCO3- had little effect. However, chloride loading of vesicles resulted in marked stimulation of sulfate uptake at pH 5.0. It appears that sulfate and protons exit lysosomes in exchange for chloride by a specific, pH-regulated anion transport system. PMID- 2211649 TI - Identification of the ATP-binding domain of vaccinia virus thymidine kinase. AB - Although small in size (20 kDa), the vaccinia virus (VV) thymidine kinase protein (EC 2.7.1.21 TK) is a relatively complex enzyme which must contain domains involved in binding both substrates (ATP and thymidine) and a feedback inhibitor (dTTP), as well as sequences directing the association of individual protein monomers into a functional tetrameric enzyme. Alignment of predicted amino acid sequences of the thymidine kinase genes from a variety of sources was used to identify highly conserved regions as a first step toward locating potential regions housing essential domains. A conserved domain (domain I) near the amino terminus of VV TK protein had characteristics consistent with a nucleotide binding site. Analysis of the nucleotide substrate specificity of VV TK indicated that ATP acts as the major phosphate donor for thymidine phosphorylation while GTP, CTP, and UTP were inefficient substrates. Site-directed mutagenesis was performed on domain I to generate 11 mutant enzymes. Comparison of the wild-type and mutant proteins with regard to enzyme activity revealed that two of the mutant enzymes, T18 and S19, exhibited enhanced enzyme activity (3.73-fold and 1.35-fold, respectively) relative to the control. The other mutations introduced led to greatly reduced levels of enzyme activity which correlated with a reduced or altered ability of the mutant enzymes to bind ATP as determined by ATP-agarose affinity chromatography. Wild-type VV TK bound to an ATP affinity column could also be eluted with dTTP. Glycerol gradient separation of wild-type TK in the presence or absence of dTTP indicated that dissociation of the tetrameric complex was not the means by which enzymatic inhibition was achieved. Taken together, these results suggest that (i) domain I (amino acids 11-22) of the VV TK corresponds to the ATP-binding site, and (ii) that dTTP is able to interfere with ATP binding, either directly or indirectly, and thereby inhibit enzymatic activity without dissociating the native enzyme. PMID- 2211650 TI - Characterization of the equilibrium binding of Xenopus transcription factor IIIA to the 5 S RNA gene. AB - A nitrocellulose filter-binding assay has been developed to study the interaction of Xenopus transcription factor IIIA (TFIIIA) with its specific binding site on the 5 S RNA gene. The protein binds to a DNA restriction fragment containing a Xenopus oocyte 5 S RNA gene (5 S DNA) with an apparent association constant of 1.90 x 10(9) M-1 in 0.1 M salt, pH 7.5, at 22 degrees C. Under these assay conditions, the protein has approximately a 100-fold lower binding affinity for DNA fragments that do not contain a 5 S RNA gene. Analysis of the temperature dependence of the binding of TFIIIA to 5 S DNA indicates that the interaction is largely enthalpy driven at temperatures above 19 degrees C, while it is largely entropy driven at lower temperatures. One molecule of TFIIIA binds per 5 S RNA gene, and this bimolecular complex dissociates with first order kinetics, having a half-life of 15.6 min. The DNA binding activity of the protein exhibits a broad pH optimum from 6.0 to 8.0, and is optimal at 5 mM MgCl2 decreasing rapidly at higher divalent ion concentrations. The specific binding of TFIIIA to 5 S DNA is insensitive to the identity of the monovalent cation present in the binding buffer. In comparison, the anion effects on DNA binding are dramatic, with a 100 fold decrease in binding affinity observed to follow the lyotropic series. This result suggests that there are several specific anion-binding sites on TFIIIA. Determination of the monovalent salt dependence of the association constant revealed that as many as 8 lysine-phosphate type ionic bonds are formed in the TFIIIA-DNA complex. PMID- 2211651 TI - Regulation of the expression of Gal alpha 1-3Gal beta 1-4GlcNAc glycosphingolipids in kidney. AB - Previous studies (Galili, U., Clark, M. R., Shohet, S. B., Buehler, J., and Macher, B. A. (1987) Proc. Natl. Acad. Sci. U. S. A. 84, 1369-1373; Galili, U., Shohet, S. B., Korbrin, E., Stults, C. L. M., and Macher, B. A. (1988) J. Biol. Chem. 263, 17755-17762) have established that there is a unique evolutionary distribution of glycoconjugates carrying the Gal alpha 1-3Gal beta 1-4GlcNAc epitope. These glycoconjugates are expressed by cells from New World monkeys and non-primate mammals, but not by cells from humans, Old World monkeys, or apes. The lack of expression of this epitope in the latter species appears to result from the suppression of gene expression for the enzyme UDP-galactose:nLc4Cer alpha 1-3-galactosyltransferase (alpha 1-3GalT) (Joziasse, D. H., Shaper, J. H., Van den Eijnden, D. H., Van Tunen, A. J., and Shaper, N. L. (1989) J. Biol. Chem. 264, 14290-14297). Although many non-primate species are known to express this carbohydrate epitope, the nature (i.e. glycoprotein or glycosphingolipid) of the glycoconjugate carrying this epitope is only known for a few tissues in a few animal species. Furthermore, it is not known whether all animal species express this epitope in the same tissues. We have investigated these questions by analyzing the glycosphingolipids in kidney from several non-primate animal species. Immunostained thin layer chromatograms of glycosphingolipids from sheep, pig, rabbit, cow, and rat kidney with the Gal alpha 1-3Gal beta 1-4GlcNAc glycosphingolipid-specific monoclonal antibody, Gal-13, demonstrated that kidney from all of these species except rat contained Gal alpha 1-3Gal beta 1-4GlcNAc neutral glycosphingolipids. A lack of expression of Gal alpha 1-3Gal beta 1 4GlcNAc glycosphingolipids in rat may be due to the lack of expression of the enzyme (alpha 1-3GalT) which catalyzes the formation of the Gal alpha 1-3Gal nonreducing terminal sequence of these compounds or to the lack of expression of glycosyltransferases which are necessary for the synthesis of the neolacto core structure of these compounds. These possibilities were evaluated in two ways. First, the three enzymes (UDP-N-acetylglucosamine:LacCer beta 1-3-N-acetyl glucosaminyltransferase, UDP-galactose:Lc3Cer beta 1-4-galactosyltransferase, and alpha 1-3GalT) involved in the synthesis of the Gal alpha 1-3Gal beta 1-4GlcNAc glycosphingolipids were assayed using an enzyme-linked immunosorbent assay-based assay system and carbohydrate sequence-specific monoclonal antibodies. Second, TLC immunostaining was done to determine if the glycosphingolipid precursors (i.e. Lc3Cer and nLc4Cer) are expressed in rat kidney. Interestingly, rat kidney had a relatively high level of alpha 1-3GalT activity compared with the other animals tested.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2211652 TI - RNA primary sequence or secondary structure in the translational initiation region controls expression of two variant interferon-beta genes in Escherichia coli. AB - Efficient expression in Escherichia coli (E. coli) of the human interferon-beta gene (IFN-beta) gene and of a chemically synthesized IFN-beta gene variant (506 base pairs; synIFN-beta) adapted to the E. coli codon usage, both fused to the E. coli atpE ribosome-binding site, is controlled either by primary sequence or by mRNA secondary-structure in the translational initiation region. High level expression of the natural human atpE/IFN-beta gene fusion is governed by the nucleotide composition preceding the initiator codon AUG. A single U----C exchange in the -2 or -1 position preceding the initiator codon AUG reduces the translational efficiency from 18% of total cellular protein to only 8% or 4%, respectively, while both U----C substitutions reduce IFN-beta expression below 1%. These sequence alterations interfere with efficient ribosome binding as revealed by toeprinting. They provide further evidence for the influence of the anticodon-flanking regions of tRNA(fMet) upon the initiation rate of translation. In contrast, translation of the synthetic variant atpE/synIFN-beta gene fusion is controlled by a moderately stable stem-loop structure (delta G = -4 kcal/mol; 37 degrees C) located within the coding region and overlapping the 30 S ribosomal subunit attachment site. That the stability of the hairpin interferes with the initiation of translation is inferred from site-directed mutagenesis and toeprint analyses. mRNA half-life in these variants is positively correlated with the rate of translation and involves two major endonucleolytic cleavage site 5'-upstream of the Shine-Dalgarno region. PMID- 2211653 TI - Stopped flow and steady state kinetic studies of the effects of metabolites on the soluble form of NADP+:isocitrate dehydrogenase. AB - The cytosolic form of NADP+:isocitrate dehydrogenase, a primary source of the NADPH required for de novo fatty acid synthesis in lactating bovine mammary gland, was studied to determine possible mechanisms of regulation by metabolites. Stopped flow kinetics showed a distinct lag time, followed by attainment of an apparently linear final velocity. Direct nonlinear regression analyses of the reaction progress curves allowed for the calculation of the rate constant (kappa) for the transition of the enzyme from an inactive to an active form; this transition is best catalyzed by its metal-substrate complex. Preincubation with metal-substrate or metal-citrate nearly abolished the lag by increasing kappa 10 fold. In steady state experiments, analyses of velocity versus metal-citrate complex as a binding isotherm, following the assumptions of Wyman's theory of thermodynamic linkage, showed that binding of metal-citrate complex could both activate and inhibit the enzyme. This analysis suggested: (a) activation by binding to sites with an average dissociation constant of 0.25 mM; (b) inhibition by binding to sites with an average dissociation constant of 3.83 mM; and (c) modulation (reactivation) by binding to sites with an average dissociation constant of 1.54 mM. Concentration ranges observed for these transitions are compatible with physiological conditions, suggesting that complexes of metal citrate and metal-isocitrate serve to modulate the activity of NADP+:isocitrate dehydrogenase. PMID- 2211654 TI - Spectroscopic evidence for ligand-induced conformational change in NADP+:isocitrate dehydrogenase. AB - Conformational changes induced by binding of ligands to cytosolic NADP(+) specific isocitrate dehydrogenase from lactating bovine mammary gland were assessed using circular dichroism and fluorescence techniques. The secondary structure of isocitrate dehydrogenase, as monitored by CD spectra in the far-UV region, is unaltered by enzyme-ligand interactions; in contrast, dramatic changes occur in the near-UV region (270-290 nm) assigned to tyrosine and/or solvent exposed tryptophan residues. Both the coenzyme analog, 2'-phosphoadenosine 5' diphosphoribose, and NADPH have an effect on the CD spectrum which is opposite to that produced by metal complexes of either isocitrate or citrate. A CD band at 292 nm assigned to approximately 2 tryptophan residues in a hydrophobic environment is unchanged by binding of substrate or coenzyme. Approximately 30% of the intrinsic fluorescence of isocitrate dehydrogenase, corresponding to approximately 2 tryptophan residues, is not quenched by acrylamide in the absence of 6.3 M guanidine hydrochloride and remains unquenched in the enzyme-substrate complex. The constancy in the proportion of buried and exposed tryptophan residues implicates tyrosine in the observed near-UV CD spectral changes. Since binding of ligands does not influence quaternary structure (Seery, V.L., and Farrell, H. M., Jr. (1989) Arch. Biochem. Biophys. 274, 453-462), activation of isocitrate dehydrogenase may be related to a substrate-induced conformational transition. PMID- 2211655 TI - Variation of cofactor levels in Escherichia coli. Sequence analysis and expression of the pncB gene encoding nicotinic acid phosphoribosyltransferase. AB - The pncB gene from Escherichia coli, which encodes nicotinic acid phosphoribosyltransferase (EC 2.4.2.11), was cloned on a 1.5-kilobase TaqI-EcoRI fragment. Its position on the E. coli chromosome was determined at 20.8 min between the asnS and pepN loci. The nucleotide sequence of the gene and the transcription and translation initiation sites were determined. Expression of pncB on a multicopy plasmid leads to a 25-fold increase in nicotinic acid phosphoribosyltransferase activity. Growth of E. coli in the presence of nicotinic acid leads to strong repression of nicotinic acid phosphoribosyltransferase activity, indicating that the cloned pncB sequence contains its own control sequences. It is shown that increased nicotinic acid phosphoribosyltransferase activity effects a 5-fold increase in the intracellular concentration of NAD. The cloned pncB gene can therefore be used as a tool to raise intracellular cofactor levels. PMID- 2211656 TI - In situ cross-linking of human erythrocyte band 3 by bis(sulfosuccinimidyl)suberate. Evidence for ligand modulation of two alternate quaternary forms: covalent band 3 dimers and noncovalent tetramers formed by the association of two covalent dimers. AB - Treatment of intact human erythrocytes with bis(sulfosuccinimidyl)suberate converted band 3 to two species with lower electrophoretic mobility in sodium dodecyl sulfate (SDS). The presence of the noncovalent anion transport inhibitor, 4,4'-dinitrostilbene-2,2'-disulfonate, promoted the lowest mobility form, while a closely related analogue, 4,4'-diisothiocyano-2,2'-stilbenedisulfonate, did not. Ferguson analysis of the electrophoretic behavior of the two slowly migrating bands strongly suggested that they represented dimers and tetramers of band 3. Increasing the temperature of the SDS solution to greater than 60 degrees C quantitatively converted the tetrameric species to the dimeric form. We conclude that band 3 can be intermonomerically cross-linked by bis(sulfosuccinimidyl)suberate as covalent dimers within two alternate quaternary forms in a manner modulated by the ligand occupying the intramonomeric stilbenedisulfonate site. In one form, band 3 covalent dimers are noncovalently associated as a SDS-resistant tetramer, while in the other form, covalent dimers are not so associated. There is no obvious relationship between ligand stereochemistry and the resulting quaternary form, suggesting that the two forms reflect alternate allosterically modulated porter quaternary structures. The significance of these two quaternary states to the transport or the ankyrin binding functions of band 3 is unknown. PMID- 2211657 TI - Purification and characterization of functional recombinant alpha-amidating enzyme secreted from mammalian cells. AB - A rat alpha-amidating enzyme (alpha-AE) cDNA has been expressed in mouse C127 cells using a bovine papilloma virus vector in which transcription was regulated by the mouse metallothionein 1 promoter. The cDNA encoding the full length alpha AE protein was modified to terminate translation at a site preceding the transmembrane and cytoplasmic domains, thereby enabling functional enzyme to be secreted into the medium. Purification of recombinant alpha-AE to homogeneity indicated that the enzyme was synthesized and secreted as two proteins of 75-77 kDA. The observed heterogeneity was due to inefficient glycosylation at Asn660, as demonstrated by glycopeptidase F digestion. Using the synthetic peptide, dansyl-Tyr-Val-Gly, the specific activity of the recombinant enzyme at pH 7.0 was found to be 1.4 mumol/min/mg and the Km of the enzyme was determined to be 3 microM. The purified recombinant enzyme has maximal activity at pH 4.5-5.5; however, a rapid inactivation of the enzyme occurs in acidic solutions in vitro. This inactivation is diminished when activity is measured at pH 7.0-10.0. The availability of large amounts of readily purified, active recombinant alpha-AE should allow detailed probing of reaction mechanism, copper coordination chemistry, and turn-over-based inactivation events. PMID- 2211658 TI - Characterization of recombinant tick anticoagulant peptide. A highly selective inhibitor of blood coagulation factor Xa. AB - Tick anticoagulant peptide (TAP) is a potent, highly selective inhibitor of blood coagulation factor Xa (Waxman, L., Smith, D. E., Arcuri, K. E., and Vlasuk, G. P. (1990) Science, 248, 593-596). Further detailed studies pertaining to the in vitro and in vivo evaluation of TAP require quantities of the inhibitor which cannot be isolated from ticks. To overcome this limitation we describe here the characterization of recombinant TAP (rTAP) secreted by Saccharomyces cerevisiae. Expression of rTAP was obtained using a chimeric gene containing a fusion between sequences encoding the secretory preproleader of the yeast mating pheromone alpha factor and a synthetic sequence encoding the 60-amino acid inhibitor under the transcriptional control of a galactose-inducible promoter. Recombinant S. cerevisiae were found to secrete biologically active rTAP into the extracellular medium at levels of 0.1-0.15 g/liter. The secreted inhibitor was purified to homogeneity and found to be indistinguishable from the native inhibitor with respect to several criteria, including primary structure, amino acid composition, and electrophoretic mobility. In addition, purified rTAP and native TAP exhibited similar stoichiometric inhibition of factor Xa in vitro. The in vivo efficacy of rTAP was demonstrated using a model of low grade disseminated intravascular coagulation where the purified inhibitor was shown to significantly inhibit thromboplastin-induced fibrinopeptide A generation following an infusion into conscious rhesus monkeys. The availability of rTAP will allow a detailed evaluation of the in vitro and in vivo properties of this highly specific and potent factor Xa inhibitor. PMID- 2211659 TI - The subunit S1 is important for pertussis toxin secretion. AB - Pertussis toxin is a protein containing five noncovalently linked subunits which are assembled into the monomer A (containing the subunit S1) and the oligomer B (containing subunits S2, S3, S4, and S5 in a 1:1:2:1 ratio). Each of the five subunits is synthesized as a precursor containing a secretory leader peptide and is secreted into the periplasm of Bordetella pertussis where the five subunits are assembled into the oligomeric structure and then released into the culture medium. In the absence of subunit S3 the remaining subunits are not secreted into the medium, thus suggesting that the assembled structure is necessary for the release of the toxin into the supernatant. In this study we describe four B. pertussis mutants which secrete into the medium low amounts of the B oligomer of pertussis toxin. These mutants have single or multiple changes in the gene encoding the S1 subunit and synthesize S1 proteins with altered conformation which are not assembled into the holotoxin and are apparently degraded in the periplasm. These data indicate that while the B oligomer alone has the structural information necessary for the extracellular export of pertussis toxin, the S1 subunit is required for its efficient release into the medium. PMID- 2211660 TI - Biosynthesis and processing of renal mitochondrial glutaminase in cultured proximal tubular epithelial cells and in isolated mitochondria. AB - Primary cultures of rat renal proximal tubular epithelial cells were used to characterize the biosynthesis and processing of the mitochondrial glutaminase. When the cells were labeled with [35S]methionine in the presence of 20 microM carbonylcyanide m-chlorophenylhydrazone, only a 72-kDa peptide, which co-migrates with the primary translation product of the glutaminase mRNA, was immunoprecipitated. At lower concentrations of carbonylcyanide m chlorophenylhydrazone, the 68- and 65-kDa peptides that are characteristic of the mature glutaminase and a 71-kDa peptide were synthesized. Pulse-chase experiments suggest that the 72-kDa cytosolic precursor could be quantitatively chased to generate the mature mitochondrial species. The observed kinetics indicate that the 71-kDa species is an intermediate in the import pathway. In addition, the 65 kDa glutaminase peptide was synthesized more rapidly than the 68-kDa peptide, and the two peptides were produced in a final ratio of 3:1, respectively. These results suggest that one subunit of the tetrameric glutaminase may be subject to covalent modification. In vitro processing was also characterized by incubating isolated rat liver mitochondria with the glutaminase precursor that was produced by in vitro translation of acidotic rat renal poly(A+) RNA. This system produced an identical sequence of processing reactions. The in vitro formation of the 71 kDa intermediate required a transmembrane potential. Both the intermediate and the mature forms of the glutaminase were recovered in the mitochondria and were resistant to trypsin digestion. Thus, the glutaminase precursor is rapidly translocated across the inner mitochondrial membrane and initially processed to yield an intermediate. The intermediate is subsequently processed to yield the two peptides that constitute the mature enzyme. PMID- 2211661 TI - Deficient expression of the gene coding for decorin in a lethal form of Marfan syndrome. AB - The markedly decreased level of the messenger RNA of decorin, an abundant dermatan/chondroitin sulfate proteoglycan was found in the skin fibroblast culture of a lethally sick Marfan infant. Also, the amount of decorin polypeptide in the culture medium of the fibroblasts of this infant was markedly decreased. When the effect of interleukin-1 beta on the transcription of decorin was tested in these fibroblasts, the response was deficient as compared to control fibroblasts whereas transcription of type I and III collagen genes and versican was stimulated normally. The decreased decorin mRNA level, unresponsive to interleukin-1 beta in this lethally sick Marfan patient, stresses the significance of this proteoglycan in the formation of normal connective tissue. Furthermore, the low expression of this gene could be responsible for the connective tissue findings in this patient, representing a rare type of Marfan syndrome. The identical finding in three other, unrelated Marfan individuals suggests a more general significance of deficient decorin expression in this disease. PMID- 2211662 TI - Structural and functional analysis of two Campylobacter jejuni flagellin genes. AB - The purpose of this study was to characterize the flagellin gene of Campylobacter jejuni and to study the structure of this protein and the regulation of its synthesis. A part of the flagellin gene of C. jejuni strain 81116 was recently cloned by us. This DNA fragment was used as a probe to isolate the other homologous flagellin sequences from genomic libraries. The flagellin nucleotide sequence was determined from overlapping clones. Two copies of the flagellin gene were identified: genes fla A and fla B consisted of 1731 base pairs each, occurred as tandem repeats, and were 95% identical. Only mRNA that was transcribed from gene A was detected in flagellate cells. sigma 28-specific promoter sequences were found upstream of the transcription initiation site. Analysis of the flagellin protein sequence showed that the amino-terminal and the carboxyl-terminal regions were highly similar to other bacterial flagellins. The conserved regions can form alpha-helices with a nonpolar backbone at one side. We suggest that because these domains were conserved (i) they may be involved in polymerization or transport of flagellins or both, and (ii) they are important for maturation and stability of the flagellum. PMID- 2211663 TI - RNA polymerase II subunit RPB10 is essential for yeast cell viability. AB - The Saccharomyces cerevisiae gene encoding the smallest RNA polymerase II subunit, RPB10, was isolated and sequenced. The gene for this subunit is present in single copy and maps to chromosome XV, where two other yeast RNA polymerase II subunits, RPB2 and RPB8, reside. The RPB10 sequence predicts a protein only 46 amino acids in length with a molecular mass of 5400 daltons. Sporulation and tetrad analysis of diploid cells containing one copy of the RPB10 gene and one copy of HIS3 in place of the RPB10 gene revealed that the RPB10 subunit is essential for viability. PMID- 2211664 TI - Molecular cloning of an amino acid-regulated mRNA (amino acid starvation-induced) in rat hepatoma cells. AB - Using the combination of a subtracted library and differential hybridization, a 409-base pair cDNA was identified that corresponds to a mRNA that is induced 2-3 fold when rat Fao hepatoma cells are subjected to amino acid starvation for 12 h. While this mRNA species was induced during starvation, others such as beta-actin, Cu-Zn superoxide dismutase, glyceraldehyde-3-P, and histone H4 were decreased in abundance to 25-50% of their original levels. The induction of the amino acid starvation-induced (ASI) mRNA was repressed when starved cells were returned to a medium supplemented with amino acids. Tissue distribution analysis showed the ASI mRNA, approximately 650 base pairs in length, to be present in every rat tissue tested. The cDNA clone has been sequenced and appears to correspond to the 3' most end of the mRNA. The cDNA sequence includes the poly(A) tail, two potential polyadenylation signal sequences, and an open reading frame that we presume to be a portion of the coding sequence. The ASI cDNA will be used to investigate the molecular mechanisms for amino acid-dependent regulation of protein expression by mammalian cells. PMID- 2211665 TI - Transcriptional regulation of the liver beta-galactoside alpha 2,6 sialyltransferase by glucocorticoids. AB - Hepatic expression of the beta-galactoside alpha 2,6-sialyltransferase is at least in part specified by circulatory glucocorticoids. In this report we use the glucocorticoid agonist, RU362, and the antagonist, RU486, to demonstrate the participation of the glucocorticoid receptor pathway in beta-galactoside alpha 2,6-sialyltransferase regulation. The existing pool of sialyltransferase mRNA is turned over with an approximate half-life of 13 h, and presence of dexamethasone does not alter this rate of degradation. By means of nuclear run-off assays and measurement of nuclear unprocessed transcripts we demonstrate that dexamethasone induction of beta-galactoside alpha 2,6-sialyltransferase mRNA in rat Reuber H35 cells is mediated by a transcriptional enhancement mechanism. The same initiation site is utilized for sialyltransferase transcription in both basal- and hormone stimulated synthesis. Sialyltransferase sequences residing upstream of this transcriptional initiation point are used to control chloramphenicol acetyltransferase expression in fusion constructs following transient transfection into H35 cells to demonstrate the presence of a functional promoter. Although no element with similarity to the known GRE consensus sequence resides within this promoter region, chloramphenicol acetyltransferase expression under the control of the sialyltransferase promoter is subject to a low (1.6-fold) but reproducible induction in response to dexamethasone. Implications of this observation to glucocorticoid regulation are discussed. PMID- 2211666 TI - Free thiols of platelet thrombospondin. Evidence for disulfide isomerization. AB - The free thiols of platelet thrombospondin (TSP) were derivatized with labeled N ethylmaleimide (NEM) or iodoacetamide (IAM). When Ca2+ was chelated with EDTA, 2.9 mol of NEM or 2.6 mol of IAM reacted/mol of native TSP. No additional thiols were found after denaturation with urea. Since TSP has three apparently identical polypeptide chains, this suggests one free thiol/polypeptide chain. Ca2+ protected all of the thiols from reaction with IAM. In Ca2+ about half the thiols reacted normally with NEM and the others were unreactive, indicating that the thiols of TSP are not identical. The number of reactive thiols as a function of [Ca2+] revealed a sigmoidal curve with a transition midpoint of 207 microM. The ability of analogs of NEM to compete for derivatization of the thiols with labeled NEM was greater with larger, more hydrophobic agents. Gel electrophoretic separation of labeled TSP that had been partially digested with thrombin and trypsin indicated that some of the label was in the C-terminal tryptic fragment but that most was in the adjacent trypsin-sensitive region. After cyanogen bromide cleavage of the labeled and reduced protein, four labeled fractions were obtained from a gel filtration column. With subsequent combinations of tryptic digestion and reversed-phase high performance liquid chromatography, labeled peptides were purified from these four fractions, and the amino acid sequences were determined. Twelve labeled cysteines were identified, each with a specific radioactivity less than that of the thiol labeling reagent, indicating that only a fraction of that cysteine in a population of TSP molecules was a free thiol at the time of derivatization. While 2 labeled cysteines are in the non-repeating C terminal portion of the molecule, the other 10 labeled cysteines are in the adjacent trypsin-sensitive type 3 repeats proposed (Lawler, J., and Hynes, R. O. (1986) J. Cell. Biol. 103, 1635-1648) as the calcium-binding region of the molecule. The disulfide bonds most sensitive to reduction by dithioerythritol were also stabilized by Ca2+, implying location in the Ca2(+)-sensitive part of the molecule. It is proposed that one equivalent of free thiol/polypeptide chain is distributed among 12 different cysteine residues through an intramolecular thioldisulfide isomerization. PMID- 2211667 TI - Selenium and amino acid composition of selenoprotein P, the major selenoprotein in rat serum. AB - Selenoprotein P is the second plasma selenoprotein to be purified. It is a glycoprotein and has been shown to be distinct from plasma glutathione peroxidase. This study characterizes selenoprotein P further. Deglycosylation of the protein shifts its migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis from Mr 57,000 to Mr 43,000, indicating it has a substantial carbohydrate component. Measurement of selenium indicates a selenium content of 7.5 +/- 1.0 atoms/molecule based on a polypeptide weight of 43,000. Amino acid analysis accounts for all the selenium as selenocysteine. The protein is also rich in cysteine (17 residues) and histidine (23 residues). Fragmentation of selenoprotein P by trypsin and by cyanogen bromide produces peptides with varying selenium content. This indicates that selenium-rich regions of the protein exist. The concentration of selenoprotein P determined by radioimmunoassay in serum from control rats is 26.3 +/- 4.5 micrograms/ml and in serum from selenium-deficient rats it is 2.7 +/- 0.8 micrograms/ml. Depletion of selenoprotein P from control serum using an immunoaffinity column indicates that over 60% of serum selenium in the rat is contained in this protein. These results demonstrate that selenoprotein P is the major form of selenium in rat serum. It is the first selenoprotein described which has more than one selenium atom/polypeptide chain. PMID- 2211668 TI - Purification and characterization of proximal sequence element-binding protein 1, a transcription activating protein related to Ku and TREF that binds the proximal sequence element of the human U1 promoter. AB - The promoter structure of the known small nuclear RNA (snRNA) genes contains two major effectors of transcriptional activity, a proximal sequence element (PSE) and a distal sequence element (DSE). In previous work, methidiumpropyl-EDTA Fe(II) footprinting was used to demonstrate the existence in human placental extracts of a protein producing footprints within the PSE and the DSE of the human U1 snRNA gene. This protein (PSE1) has now been purified to homogeneity from both human placental extract and K562 cell nuclear extract. PSE1 consists of two subunits, an alpha subunit with an apparent molecular mass of 83 kDa, and a beta subunit with an apparent molecular mass of 73 kDa in K562 nuclear extracts and 63 kDa in placental extracts. Footprinting and UV cross-linking assays indicate that purified PSE1 binds to the PSE and DSE of the U1 gene. Monoclonal antibodies were prepared which specifically recognize the individual subunits of PSE1. PSE1 is immunologically similar to and shares amino acid sequence with a protein (TREF) which binds the human transferrin receptor (HTFR) promoter. An in vitro transcription system was established for a template consisting of a minimal HTFR promoter placed upstream of the human U1 snRNA-coding region and shown by immunodepletion/addback experiments to specifically require PSE1. Transcription from the adenovirus 2 major late promoter was unaffected in these experiments. This result supports a functional role of PSE1 as a transcriptional activating protein, but its role in transcription of snRNA genes remains to be established. PSE1 also has an immunological relationship to and shares amino acid sequence with the p70 and p86 subunits of the human Ku autoantigen. Ku, PSE1, and TREF may thus be identical proteins or members of a family of heterodimeric proteins consisting of related subunits. Our results support earlier proposals that Ku may be a transcriptional activator. PMID- 2211669 TI - The c1 repressor inactivator protein coi of bacteriophage P1. Cloning and expression of coi and its interference with c1 repressor function. AB - The immC region of bacteriophage P1 contains the c1 repressor gene and its upstream region with four c1-controlled operators and four open reading frames. A c1 inactivator gene, coi, was defined by mutations in immC that suppress the virulence of the P1virC mutation. The exact location of the coi gene was not known (Scott, J.R. (1980) Curr. Top. Microbiol. Immunol. 90, 49-65). When a variety of P1 immC fragments were inserted into an expression vector, a gene product was inducible for the open reading frame 4 only. We identify this product as the c1 inactivator protein, coi by the following criteria: (a) expression of coi from a recombinant plasmid induces the P1 prophage and inhibits lysogenization of sensitive bacteria by P1; (b) all c1-controlled operator promoter elements tested in vivo are derepressed by coi; (c) a partially purified coi protein (apparent molecular weight = 4800) interacts with c1 repressor and inhibits its binding to the operator in vitro. Based on these results we refine a model for the regulation of those genes and elements within immC which participate in the decision of P1 to enter the lytic or lysogenic pathway. PMID- 2211670 TI - Feedback regulation of phospholipase C-beta by protein kinase C. AB - Treatment of a variety of cells and tissues with 12-O-tetradecanoylphorbol-13 acetate (TPA), an activator of protein kinase C (PKC) results in the inhibition of receptor-coupled inositol phospholipid-specific phospholipase C (PLC) activity. To determine whether or not the targets of TPA-activated PKC include one or more isozymes of PLC, studies were carried out with PC12, C6Bu1, and NIH 3T3 cells, which contain at least three PLC isozymes, PLC-beta, PLC-gamma, and PLC-delta. Treatment of the cells with TPA stimulated the phosphorylation of serine residues in PLC-beta, but the phosphorylation state of PLC-gamma and PLC delta was not changed significantly. Phosphorylation of bovine brain PLC-beta by PKC in vitro resulted in a stoichiometric incorporation of phosphate at serine 887, without any concomitant effect on PLC-beta activity. We propose, therefore, that rather than having a direct effect on enzyme activity, the phosphorylation of PLC-beta by PKC may alter its interaction with a putative guanine nucleotide binding regulatory protein and thereby prevent its activation. PMID- 2211672 TI - Entrapment of purified alpha-hemoglobin chains in normal erythrocytes. A model for beta thalassemia. AB - Altered membrane proteins have been previously described in beta thalassemia and are thought to play an important role in the shortened erythrocyte survival. To investigate the mechanism by which these changes occur, purified heme-containing alpha-hemoglobin chains were entrapped within normal erythrocytes by reversible osmotic lysis. These resealed cells exhibited normal hemoglobin concentration, cell volume, deformability, and no substantial modifications of membrane proteins. Incubation (37 degrees C; up to 20 h) of the alpha-chain-loaded cells resulted in increasing amounts of membrane-associated alpha-chains. This was associated with concurrent decreases in the protein concentrations and reactive thiol groups of spectrin, ankyrin, and actin as determined by gel electrophoresis. The decreases in membrane protein concentration and reactive thiol groups after 20 h of incubation were closely correlated (R2 = 0.947) in the alpha-chain-loaded cells. Indicative of increased oxidant stress within the alpha chain-loaded erythrocytes, methemoglobin generation was also significantly increased in the alpha-chain-loaded erythrocytes. In addition, entrapment of alpha-chains led to a progressive and significant decrease in erythrocyte deformability. Thus, the entrapment of purified alpha-chains in normal erythrocytes resulted in structural and functional abnormalities very similar to that observed in beta-thalassemic erythrocytes in vivo. The model described provides a means by which the fate of excess alpha-chains, their pathophysiological effects, as well as possible therapeutic approaches to thalassemias can be examined. PMID- 2211671 TI - Purification and expression of gCap39. An intracellular and secreted Ca2(+) dependent actin-binding protein enriched in mononuclear phagocytes. AB - A protein of approximately 40 kDa was the major Ca2(+)-binding protein purified by Ca2(+)-dependent hydrophobic affinity chromatography from the cell lysates and conditioned media of RAW macrophages. Other Ca2(+)-binding proteins, including several annexins (calelectrins), S100-like proteins, and calmodulin, were less abundant and preferentially found in the cell lysates. Amino acid sequences of tryptic fragments from the purified 40-kDa protein revealed its identity to gCap39, an actin-binding protein encoded by a cDNA isolated on the basis of its homology with gelsolin. When an expression vector containing the gCap39 coding region was transfected into COS cells, high levels of gCap39 were found in both the cells and conditioned media, whereas annexins were only present in the cells. gCap39 could also be purified from human plasma where it appeared to be a minor component. No signal sequence was detected in the primary structure of gCap39 and the secreted and intracellular forms of gCap39 are of identical size, suggesting that unlike gelsolin, the mechanism of gCap39 secretion may not depend on a signal sequence. The high concentration of gCap39 in macrophages and its constitutive secretion as well as intracellular retention suggest that this protein may have a dual role in macrophage function, namely that of a Ca2(+)- and polyphosphoinositide-regulated intracellular modulator of the cytoskeleton as well as that of a secreted protein involved in the clearance of actin from the extracellular environment. PMID- 2211673 TI - Combined lipase deficiency in the mouse. Evidence of impaired lipase processing and secretion. AB - Newborn combined lipase-deficient (cld) mice have severe hypertriglyceridemia associated with a marked decrease of lipoprotein lipase (LPL) and hepatic lipase (HL) activities. Since the cld mutation and lipase genes reside on separate chromosomes, combined lipase deficiency cannot result from defects occurring within the LPL or HL structural genes. To elucidate the biochemical basis of this trans-acting defect, cld mice were compared to unaffected littermates for changes in lipase mRNA levels, rates of synthesis, and posttranslational processing and secretion. LPL and HL mRNA levels in cld liver and LPL in cld heart were comparable to controls; corresponding lipase synthetic rates were modestly decreased by about 30%. However, these reduced synthetic rates were not lipase specific, since the rates of apolipoprotein (apo) A-I and apoA-II synthesis in cld liver were similarly decreased. Despite LPL synthetic rates that were 70% of controls, LPL mass in cld postheparin plasma was markedly reduced to only 7% of control values, suggesting that the majority of LPL is not secreted but remains intracellular. Consistent with a lipase secretory defect, neither the LPL nor HL oligomannosyl forms were converted to their respective complex forms in cld tissues, indicating that the lipases had failed to move from the endoplasmic reticulum/cis-Golgi to the medial/trans-Golgi network. In addition, the majority of intracellular LPL was catalytically inactive, since LPL specific activity (units/mg LPL protein) in cld heart, kidney, and brain was reduced 80-97%. In contrast to the severe impairment of lipase posttranslational processing and secretion, cld mouse plasma contained normal levels of another secretory N-linked glycoprotein, adipsin, with its oligosaccharide chains fully processed to the complex form. Thus, the cld mutation appears not to globally disrupt the secretion of all N-linked glycoproteins, but rather selectively impairs LPL and HL at points essential to their normal intracellular transport and secretion. PMID- 2211674 TI - Determination of the amounts of the protein synthesis initiation and elongation factors in wheat germ. AB - Previous work by Browning et al. (Browning, K. S., Lax, S. R., Humphreys, J., Ravel, J. M., Jobling, S. A., and Gehrke, L. (1988) J. Biol. Chem. 263, 9630 9634) indicated that wheat germ extracts do not contain sufficient amounts of some of the protein synthesis initiation factors to obtain optimal translation of all mRNAs. In this investigation, a quantitative enzyme-linked immunosorbent assay was used to determine the amounts of eukaryotic initiation factors (eIF) 2, 3, 4A, 4F, and (iso)4F as well as the amounts of 40 S ribosomal subunits and elongation factors (EF) 1 alpha and 2 present in wheat germ extracts. EF-1 alpha is present in the highest amount (approximately 5% of the total protein), and eIF 4F is present in the lowest amount (approximately 0.03% of the total protein). The micromolar amounts of the factors and ribosomes are as follows: EF-1 alpha, 34; EF-2, 5.2; eIF-2, 1.5; eIF-3, 0.7; eIF-4A, 3.0, eIF-4F, 0.09; eIF-(iso)4F, 0.8; and 40 S ribosomal subunits, 3.2. The molar ratios of the factors to 40 S ribosomal subunits are approximately 11:1 for EF-1 alpha, 1.6:1 for EF-2, 0.45:1 for eIF-2, 0.2:1 for eIF-3, 0.9:1 for eIF-4A, 0.03:1 for eIF-4F, and 0.25:1 for eIF-(iso)4F. These findings strongly suggest that the concentrations of the initiation factors, particularly those factors required for the binding of mRNA to ribosomes, may play a major role in regulating the translation of mRNAs within the cell. PMID- 2211676 TI - Expression of actin in Escherichia coli. Aggregation, solubilization, and functional analysis. AB - Wild type Dictyostelium discoideum actin (42 kDa) and a truncated form of actin were expressed in Escherichia coli. Amino-terminal sequencing indicated that the truncated species was composed of two peptides, which were the result of internal translation initiation at Met-119 and Met-123. After sonication or French press lysis, all of the actin was present in highly insoluble aggregates. When bacteria were lysed directly into Sarkosyl detergent, most of the actin was soluble, and greater than 50% remained soluble after Sarkosyl was removed. Full-length wild type actin was purified using DNase I affinity chromatography and gel filtration. This species was able both to polymerize and to bind myosin in an ATP-sensitive manner, indicating it was native. Affinity chromatography demonstrated that the truncated form of actin bound DNase I to the same extent as actin synthesized in eukaryotes, indicating the applicability of this approach to mutant forms of actin. Thus, lysis procedures utilizing Sarkosyl may prove useful in isolating some of the other proteins which are normally soluble but become insoluble after bacterial expression. PMID- 2211675 TI - A merozoite receptor protein from Plasmodium knowlesi is highly conserved and distributed throughout Plasmodium. AB - The 66-kDa merozoite surface antigen (PK66) of Plasmodium knowlesi, a simian malaria, possesses vaccine-related properties that are thought to originate from a receptor-like role in parasite invasion of erythrocytes. We report the complete sequence of PK66 which allowed the demonstration that highly conserved analogues exist throughout Plasmodium including a recently reported gene from P. falciparum (Peterson, M. G., Marshall, V. M., Smythe, J. A., Crewther, P. E., Lew, A., Silva, A., Anders, R. F., and Kemp, D. J. (1989) Mol. Cell. Biol. 9, 3151-3155). These analogues are highly promising vaccination candidates. The distribution of PK66 changes after schizont rupture in a coordinate manner associated with merozoite invasion. The protein is concentrated at the apical end prior to rupture, following which it can distribute itself entirely across the surface of the free merozoite. During invasion, immunofluorescence studies suggest that, PK66 is excluded from the erythrocyte at, and behind, the invasion interface. PMID- 2211677 TI - Age-dependent decrease in the heat-inducible DNA sequence-specific binding activity in human diploid fibroblasts. AB - In order to gain a better understanding of the molecular mechanism of the attenuated heat shock response in aging diploid fibroblasts (Liu, A. Y.-C., Lin, Z., Choi, H.-S., Sorhage, F., and Li, B. (1989) J. Biol. Chem. 264, 12037-12045), we examined the regulation of a heat-inducible, heat shock element (HSE) sequence specific binding protein in IMR-90 diploid fibroblasts. Using gel retardation assay, we showed that the HSE binding activity in extracts of IMR-90 cells was very dependent on heat shock of the cells; that the induction was transient with a maximal increase observed at 1 h of heat shock. Significantly, the level of this heat-inducible HSE-binding activity was age-dependent, being high in young cells and low in old cells. By Scatchard analysis, we determined that this difference in HSE binding in young and old cells was not due to a change in the affinity of the binding, rather the level of the heat-inducible HSE-binding activity was different. The equilibrium dissociation constants (Kd) were estimated to be 30, 25, and 31 pM for cells with population-doubling levels of 22, 35, and 45, respectively; the corresponding Bmax values were 0.087, 0.042, and 0.0059 pmol of 32P-HSE bound per mg of whole cell extract protein. The decreased 32P-HSE-binding activity in the old cells was not a reflection of global alteration of many transcription factors; assay of the DNA binding activity of activating transcription factor showed little difference as a function of age. Experiments of mixing extracts from young and old cells provided evidence of a dominant inhibitor of the HSE-binding activity in old cells. Probing of protein blots with 32P-HSE showed that the subunit molecular weight of the HSE-binding protein was 83,000 in both young and old cells. The pattern of regulation of this HSE-binding protein upon heat shock and cell aging as well as the identity, in DNA sequence specificity and subunit molecular weight, of this protein with that of the human heat shock gene transcription factor suggest that the HSE-binding protein is involved in the transcriptional activation of hsp genes in IMR-90 cells. We concluded that there was an age-associated decrease in the heat shock gene transcription factor DNA-binding activity and that this could account for the attenuated heat shock gene expression in aging diploid cells. PMID- 2211678 TI - Identification of retinal insulin receptors using site-specific antibodies to a carboxyl-terminal peptide of the human insulin receptor alpha-subunit. Up regulation of neuronal insulin receptors in diabetes. AB - Insulin receptor-specific polyclonal antipeptide serum was generated against a synthetic pentadecapeptide (residues 657-670) of the deduced amino acid sequence of human insulin proreceptor cDNA for use in the analysis of insulin receptors in the retina. The affinity-purified antibodies recognized peptide antigen but not keyhole limpet hemocyanin as determined by dot blot analysis and solid phase radioimmunoassay. Addition of either synthetic peptide or the affinity-purified serum had no effect on 125I-insulin binding to placental membranes or to cells in culture. alpha-Subunits of approximately 125 kDa from human placental membranes and liver membranes were labeled by immunoblot analysis with this antiserum. In membranes isolated from human retina and brain, two classes of alpha-subunits of approximately 125 and 115 kDa were detectable. The 115-kDa subunit was neuraminidase resistant whereas the 125-kDa subunit was digested to a band of 115 kDa, indicating that these bands represent peripheral and neuronal receptors, respectively. Analysis of human retinas obtained from type I diabetic donors revealed an increased level of neuronal receptor as compared with normal retinas. These data indicate that human retina expresses neuronal insulin receptor subtypes that are up-regulated in diabetes. PMID- 2211679 TI - Brain-type glucose transporter (GLUT-1) is selectively localized to the blood brain barrier. Studies with quantitative western blotting and in situ hybridization. AB - The hypothesis that the GLUT-1 glucose transporter isoform is expressed selectively in brain at the capillary endothelium, i.e. the blood-brain barrier (BBB), was tested by using quantitative Western blotting, cytochalasin B binding, and in situ hybridization in bovine brain cortex. Purified human red cell glucose transporter was used as the standard for quantitative Western blots, because the mobility of the human erythrocyte and BBB glucose transporters in electrophoretic gels was identical. The concentration of immunoreactive glucose transporter in bovine BBB plasma membranes was 10.8 +/- 0.9 pmol/mgp (mean +/- S.E., n = 6). This value was not statistically different from the estimate of the maximal binding sites of D-glucose-displaceable [3H]cytochalasin B binding in the BBB membrane preparations, 11.7 +/- 3.5 pmol/mgp. In situ hybridization experiments using 35S-labeled antisense and sense riboprobes corresponding to nucleotides 385 932 of the GLUT-1 cDNA showed prominent hybridization of the antisense probe over brain microvascular endothelium, but no hybridization over neuropil greater than that found with the 35S-labeled sense probe. These studies are consistent with the following conclusion: (a) essentially 100% of the glucose transporter binding sites at the BBB can be accounted for by the GLUT-1 isoform; (b) in situ hybridization studies confirm previous Northern blot analysis and indicate the GLUT-1 gene is expressed selectively in microvascular endothelium in brain with minimal, if any, expression of this gene in neurons or glial cells in vivo. PMID- 2211680 TI - Regulation of hexose transport in aortic endothelial cells by vascular permeability factor and tumor necrosis factor-alpha, but not by insulin. AB - Vascular permeability factor (VPF) is mitogenic for bovine aortic endothelial (BAE) cells, whereas tumor necrosis factor (TNF) is cytostatic and was found to completely block the mitogenic response to VPF. In contrast to the apparently antagonistic mitogenic effects that these two factors elicit, chronic exposure of BAE cells to either VPF of TNF resulted in significant (about 3-fold) increases in the rates of hexose transport. The concentrations required for half-maximal stimulation were 2 ng/ml (40 pM) for TNF and 4 ng/ml (100 pM) for VPF. Exposure to both factors simultaneously resulted in a greater stimulation of transport (about 7-fold) than exposure to either factor alone. Northern blot analysis indicated that the amount of message for the GLUT-1/erythrocyte form of the glucose transporter was specifically increased by treatment with VPF (5-fold), TNF (25-fold), or to both cytokines together (35-fold). Expression of mRNAs for the insulin-sensitive muscle/adipose transporter (GLUT-4), brain/fetal skeletal muscle transporter (GLUT-3), or the hepatic transporter (GLUT-2) were not detected in either control or treated cells. Acute or chronic exposure to insulin (10(-9) to 10(-6) M) did not activate hexose transport in BAE cells. Thus, glucose transport in aortic endothelial cells can be up-regulated by either VPF, a growth stimulator, or by TNF, a growth inhibitor, but not by insulin. The additive effect of the two cytokines together may be important in the control of increased glucose metabolism at sites of inflammation. PMID- 2211681 TI - Ca2+/calmodulin kinase is activated by the phosphatidylinositol signaling pathway and becomes Ca2(+)-independent in PC12 cells. AB - Hormonal activation of the phosphatidylinositol (PI) signaling system initiates a biochemical pathway that bifurcates to increase cellular levels of diacylglycerol and of inositol trisphosphate/Ca2+. Both Diacylglycerol and Ca2+ are known to activate protein kinase C, a primary mediator of the PI signaling system. We now find that the two limbs of the PI pathway utilize distinct multifunctional protein kinases to mediate their cellular effects. An important consequence of Ca2+ elevated by the PI signaling system, when PC12 cells are treated with bradykinin, is the activation of multifunctional Ca2+/calmodulin-dependent protein kinase. This activation stimulates autophosphorylation of CaM kinase at its regulatory domain and converts it to an active, Ca2(+)-independent species that may be a basis for potentiation of Ca2+ transients. PMID- 2211682 TI - NB-598: a potent competitive inhibitor of squalene epoxidase. AB - NB-598, (E)N-ethyl-N-(6,6-dimethyl-2-hepten-4-ynyl)-3-[(3,3'-bith iophen-5 yl)methoxy]benzene-methanamine, was found to inhibit human microsomal squalene epoxidase (from Hep G2 cells) in a competitive manner. NB-598 inhibited cholesterol synthesis from [14C]acetate dose dependently in Hep G2 cells and increased the intracellular radioactivity of squalene. A single oral administration of NB-598 inhibited cholesterol synthesis from [14C]acetate in rats. Moreover, multiple oral administration of NB-598 to dogs decreased serum total and low density lipoprotein cholesterol levels and increased serum squalene levels. After termination of treatment, the reduced serum cholesterol and increased squalene levels returned to their control values. PMID- 2211683 TI - Chinese hamster ovary cell mutants defective in myo-inositol transport. AB - By means of an in situ colony autoradiographic assay for the incorporation of [14C]inositol into the trichloroacetic acid-insoluble fraction, we have isolated a mutant of cultured Chinese hamster ovary cells defective in inositol transport, named mutant 648. Through comparison of the inositol uptake activity of 648 cells with that of the parental cells with various concentrations of inositol and sodium, it has been demonstrated that Chinese hamster ovary cells possess a sodium-dependent transport system for inositol, and that 648 cells lack this system. The sodium-dependent uptake is inhibited by 2,4-dinitrophenol and ouabain, and the intracellular concentration of inositol exceeds the extracellular concentration during the uptake period, indicating that it is active transport, at least partially driven by the sodium gradient generated by Na+,K(+)-ATPase. The apparent Km for inositol has been estimated to be 12.0 microM. It is inhibited by hyperglycemic concentration of D-glucose in a competitive fashion. PMID- 2211684 TI - Selective down-regulation of the pro-enkephalin gene during differentiation of a multiple neuropeptide-co-expressing cell line. AB - Regulation of co-expression of three neuropeptide genes, i.e. genes encoding enkephalin, cholecystokinin, and gastrin-releasing peptide, was studied in human neuroepithelioma cells. In nondifferentiated state, the continuous cell line SK-N MC displayed an equally high level of expression of the enkephalin, cholecystokinin, and gastrin-releasing peptide genes. By culturing in medium containing endothelial cell growth supplement the SK-N-MC cells differentiated morphologically into a cell type with neurite-like processes. After 3 days the expression of the enkephalin gene in endothelial cell growth supplement differentiated cells was significantly reduced by 75% as compared to the nondifferentiated cells, while there was no change in the expression of the cholecystokinin and gastrin-releasing peptide genes during differentiation. The results show that the enkephalin gene is selectively down-regulated during differentiation of neuroepithelioma cells. It is suggested that the down regulation is related to the transient expression of the enkephalin gene in developing brain and other organs. Thus the neuroepithelioma cell line may provide a cellular model to study the underlying molecular mechanism. PMID- 2211685 TI - Accurately initiated, enhancer-dependent transcription by RNA polymerase I in yeast extracts. AB - Nuclear extracts from Saccharomyces cerevisiae support initiation by RNA polymerase I at the 35 S rRNA promoter. Initiation occurs at the same site and is stimulated by the polymerase I enhancer element to about the same extent in vitro as in vivo. PMID- 2211686 TI - Activation of lysine 2,3-aminomutase by S-adenosylmethionine. AB - Lysine 2,3-aminomutase, which catalyzes the interconversion of L-lysine and L beta-lysine, is S-adenosyl-methionine-dependent, and the adenosyl-C-5' methylene group of this coenzyme mediates the transfer of hydrogen from C-3 of lysine to C 2 of beta-lysine. We here report experiments that address the mechanism by which S-adenosylmethionine activates lysine 2,3-aminomutase. We also describe an updated and improved purification procedure that produces enzyme with a specific activity substantially higher than that previously reported. Activation of the enzyme by less than 1 mol of S-adenosyl[1-14C]methionine/mol of subunits in the presence of lysine leads to the production of [14C] methionine in a kinetically biphasic process. After 1.8 min at 30 degrees C, 10% of the 14C is reisolated as [14C] methionine, and the cleavage increases to 19% after 10 min and to 51% after 40 min. Similar experiments with S-[8-14C]adenosylmethionine produce 5' deoxy[14C]adenosine in amounts similar to the formation of methionine. The major radioactive products isolated in each case are [14C]methionine or 5' deoxy[14C]adenosine, respectively, and unchanged 14C-labeled S adenosylmethionine. These experiments support the hypothesis that activation of lysine 2,3-aminomutase involves a transfer of the 5'-deoxyadenosyl moiety from S adenosylmethionine to another species associated with the enzyme, presumably another cofactor, to form an adenosyl cofactor that functions as the proximal, hydrogen abstracting species in the mechanism. PMID- 2211687 TI - Covalent oligomerization of rat gastric mucin occurs in the rough endoplasmic reticulum, is N-glycosylation-dependent, and precedes initial O-glycosylation. AB - Rat gastric mucin undergoes extensive modifications during biosynthesis, including oligomerization, N- and O-glycosylation, and sulfation. We characterized the events in the rough endoplasmic reticulum (RER) and Golgi complex and studied how these steps are interrelated, using specific inhibitors of cellular processes. The mucin precursors oligomerize in the RER by forming intermolecular disulfide bonds. The oligomers comprise a mixture of predominantly di- and trimers of molar ratio 3:2. The oligomerized precursors are transported to the Golgi complex to form mature, oligomeric mucin by extensive O glycosylation, and sulfation. N-Glycosylation of the precursor is required for efficient oligomerization. Brefeldin A, which inhibits protein transport between RER and Golgi complex, allows oligomerization and concomitantly induces initial O glycosylation. Oligomerization and egrees from the RER precedes initial O glycosylation and are therefore independent of the latter process. PMID- 2211688 TI - Fingerprinting of near-homogeneous DNA ligase I and II from human cells. Similarity of their AMP-binding domains. AB - DNA ligases play obligatory roles during replication, repair, and recombination. Multiple forms of DNA ligase have been reported in mammalian cells including DNA ligase I, the high molecular mass species which functions during replication, and DNA ligase II, the low molecular mass species which is associated with repair. In addition, alterations in DNA ligase activities have been reported in acute lymphocytic leukemia cells, Bloom's syndrome cells, and cells undergoing differentiation and development. To better distinguish the biochemical and molecular properties of the various DNA ligases from human cells, we have developed a method of purifying multiple species of DNA ligase from HeLa cells by chromatography through DEAE-Bio-Gel, CM-Bio-Gel, hydroxylapatite, Sephacryl S 300, Mono P, and DNA-cellulose. DNA-cellulose chromatography of the partially purified enzymes resolved multiple species of DNA ligase after labeling the enzyme with [alpha-32P]ATP to form the ligase-[32P]AMP adduct. The early eluting enzyme activity (0.25 M NaCl) contained a major 67-kDa-labeled protein, while the late eluting activity (0.48 M NaCl) contained two major labeled proteins of 90 and 78 kDa. Neutralization experiments with antiligase I antibodies indicated that the early and late eluting activity peaks were DNA ligase II and I, respectively. The three major ligase-[32P]AMP polypeptides (90, 78, and 67 kDa) were subsequently purified to near homogeneity by elution from preparative sodium dodecyl sulfate-polyacrylamide gels. All three polypeptides retained DNA ligase activities after gel elution and renaturation. To further reveal the relationship between these enzymes, partial digestion by V8-protease was performed. All three purified polypeptides gave rise to a common 22-kDa-labeled fragment for their AMP binding domains, indicating that the catalytic sites of ligase I and II are quite similar, if not identical. Similar findings were obtained from the two dimensional gel electrophoresis of their AMP-binding domains in the trypsin digested protein fragments. The results also suggested that these isozymes have been derived from the same primordial DNA sequence or from the same precursor protein. The purification scheme and the data obtained will be instrumental for the further elucidation of the biological roles of various DNA ligases from human cells. PMID- 2211689 TI - 5-Methylphenazinium methylsulfate mediates cyclic electron flow and proton gradient dissipation in chromaffin-vesicle membranes. AB - When 5-methylphenazinium methylsulfate and a reductant (ascorbate or NADH) are added together to a suspension of resealed chromaffin-vesicle membranes, the pH gradient (inside acidic) and the membrane potential (inside positive) established by the H(+)-translocating adenosine triphosphatase (ATPase) are rapidly dissipated. Dissipation of the pH gradient may be observed using either the optical probe acridine orange or the weak base methylamine. Dissipation of the membrane potential may be observed using the potential-dependent dye oxonol VI. A reductant and 5-methylphenazinium methylsulfate added in combination will also abolish a K+ diffusion potential across chromaffin-vesicle membranes but not across liposome membranes. 5-Methylphenazinium methylsulfate oxidizes cytochrome b561 in chromaffin-vesicle ghosts. Ascorbate readily reduces cytochrome b561, but reduction of cytochrome b561 by NADH is greatly enhanced in the presence of 5 methylphenazinium methylsulfate. These results are consistent with a mechanism in which proton gradient dissipation (a net efflux of H+) is caused by an influx of electrons through the membrane-protein cytochrome b561 coupled with an efflux of H carried by the reduced species 5-methyl-10-hydrophenazine. Although 5 methylphenazinium has been thought to accumulate within acidic vesicles as a weak base, this accounts for neither proton gradient dissipation nor for intravesicular accumulation of the compound. PMID- 2211690 TI - Characterization of a region in mature LamB protein that interacts with a component of the export machinery of Escherichia coli. AB - It has been shown that the synthesis of an export-defective protein can interfere with the normal export process in Escherichia coli by limiting the availability of SecB protein, a component of the export apparatus (Collier, D.N., Bankaitis, V.A., Weiss, J.B., and Bassford, P.J. (1988) Cell 53, 273-283). Consistent with this observation, we find that the interference elicited by an export-defective LamB protein is a titratable response resulting from the limitation of a single ligand. We have mapped the interfering region in LamB to between amino acids 320 and 380 of the mature protein. Expression of this sequence in the form of a LacZ LamB-LacZ fusion protein elicits the export interference phenotype. Deletion of the sequence from an export-defective LamB protein eliminates the ability of this protein to interfere with the export of other secreted proteins. Together, these findings show that this sequence is both necessary and sufficient to cause export interference. Surprisingly, deletion of this sequence from an otherwise wild-type LamB protein does not cause the mutant LamB product to exhibit any obvious export defect. Based on our results, we propose that SecB interacts with both amino acids 320-380 of mature LamB and the LamB signal sequence during initiation of the export process. PMID- 2211691 TI - The presence of both the signal sequence and a region of mature LamB protein is required for the interaction of LamB with the export factor SecB. AB - In the accompanying paper (Altman, E., Bankaitis, V.A., and Emr, S.D. (1990) J. Biol. Chem. 265, 18148-18153) a putative SecB binding site was identified in the mature LamB protein. The export of wild-type LamB was unperturbed when this region was removed, however, suggesting the presence of a second site of interaction between SecB and LamB. In this paper we show that the interference caused by export-defective LamB proteins is influenced by the amount of signal sequence that is present. If a large portion of the signal sequence is deleted then the interference levels are significantly reduced. This result suggests that a region of the signal sequence contributes to the interaction of SecB with the LamB protein. Using anti-SecB affinity chromatography, we demonstrated directly that the association of SecB protein with precursor LamB is dependent on the presence of both the LamB signal sequence and the interfering region which maps to amino acids 320-380 of mature LamB. Although the interfering region is not necessary for the export of wild-type LamB under normal conditions, when the signal sequence is mutationally altered the interfering region is required to promote the efficient export of LamB protein. Also, deletion of the interfering region eliminates the ability of wild-type LamB precursor to be maintained in an export competent conformation in vivo. Collectively, our results indicate that efficient export of the LamB protein is achieved by an interaction with SecB that involves both the LamB signal sequence and the interfering region in mature LamB. PMID- 2211692 TI - X-ray structure of a (alpha-Man(1-3)beta-Man(1-4)GlcNAc)-lectin complex at 2.1-A resolution. The role of water in sugar-lectin interaction. AB - We describe herein the high resolution refined x-ray structure of a trisaccharide, which is a part of the N-acetyllactosamine type glycan found in the majority of the N-glycosyl-proteins, complexed to the isolectin I. According to the potentials used by Imberty et al. (Imburty, A., Gerber, S., Tran, V., and Perez, S. (1990) Glycoconjugate J. 7, 27-54) the trisaccharide is in a low-energy state. Only one mannose moiety establishes direct hydrogen bonds with the lectin, as it is the case for monosaccharide-lectin complexes. The comparison of our trisaccharide with the one determined in solution by Warin et al. (Warin, V., Baert, F., Fouret, R., Strecker, G., Fournet, B., and Montreuil, J. (1979) Carbohydr. Res. 76, 11-22) shows that both adopt roughly the same conformation. The differences in these two sugar structures allow us to assign the role of water molecules present in the vicinity of our trisaccharide for the stabilization of this sugar-lectin complex. PMID- 2211693 TI - Cell surface labeling of glucose transporter isoform GLUT4 by bis-mannose photolabel. Correlation with stimulation of glucose transport in rat adipose cells by insulin and phorbol ester. AB - A new impermeant photoaffinity label has been used for identifying cell surface glucose transporters in isolated rat adipose cells. This compound is 2-N-4(1-azi 2,2,2-trifluoroethyl)benzoyl-1,3-bis(D-mannos-4- yloxy)-2- propylamine. We have used this reagent in combination with immunoprecipitation by specific antibodies against the GLUT4 and GLUT1 glucose transporter isoforms to estimate the relative abundance of these two transporters on the surface of the intact adipose cell following stimulation by insulin and phorbol 12-myristate 13-acetate (PMA). In the basal state, GLUT4 and GLUT1 are both present at the cell surface but GLUT4 is more abundant than GLUT1. In response to insulin, GLUT4 increases 15-20-fold and GLUT1 increases approximately 5-fold while 3-O-methyl-D-glucose transport is stimulated 20-30-fold. By contrast, PMA only induces a approximately 4-fold increase in GLUT4 while GLUT1 increases approximately 5-fold to the same level as seen with insulin. In addition, PMA stimulates 3-O-methyl-D-glucose transport approximately 3-fold to only 13% of the insulin-stimulated state. Thus GLUT4 is the major glucose transporter isoform under all conditions, and it is selectively and markedly enriched in response to insulin but not PMA which increases GLUT1 and GLUT4 equally. Furthermore, stimulation of glucose transport activity correlates closely with the appearance of GLUT4 on the cell surface in response to both insulin and PMA but does not correlate with the sum of GLUT1 and GLUT4 appearance. These results suggest that GLUT4 may be inherently more active than GLUT1 due to a higher TK (turnover/Km). PMID- 2211694 TI - Yeast tRNA-splicing endonuclease is a heterotrimeric enzyme. AB - tRNA-splicing endonuclease from the yeast Saccharomyces cerevisiae was purified to homogeneity greater than 5000-fold over a crude Triton X-100 extract of yeast total membranes, with 5% overall yield. This nuclear enzyme has the unusual heterotrimeric subunit structure alpha beta gamma (alpha = 31 kDa, beta = 42 kDa, and gamma = 51 kDa), as determined by sodium dodecyl sulfate gel electrophoresis, and has a molecular mass close to the sum of the three subunits, as determined by gel filtration of the native enzyme. From the purification, we estimate that there are approximately 100 molecules of endonuclease/cell. PMID- 2211695 TI - Identification of a region of Escherichia coli ribosomal protein L2 required for the assembly of L16 into the 50 S ribosomal subunit. AB - In vitro mutagenesis of rplB was used to generate changes in a conserved region of Escherichia coli ribosomal protein L2 between Gly221 and His231. Mutants were selected by temperature sensitivity using an inducible expression system. A mutant L2 protein with the deletion of Thr222 to Asp228 was readily distinguishable from wild-type L2 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and ribosomes from the strain overexpressing this mutant protein were characterized by sucrose density gradient centrifugation and protein composition. In addition to 30 S and 50 S ribosomal subunits, cell lysates contained a new component that sedimented at 40 S in 1 mM Mg2+ and at 48 S in 10 mM Mg2+. These particles contained mutant L2 protein exclusively, completely lacked L16, and had reduced amounts of L28, L33, and L34. They did not reassociate with 30 S ribosomal subunits and were inactive in polyphenylalanine synthesis. Other mutants in the same conserved region, including the substitution of His229 by Gln229, produced similar aberrant 50 S particles that sedimented at 40 S and failed to associate with 30 S subunits. PMID- 2211696 TI - Evidence for the nature of the link between the arabinogalactan and peptidoglycan of mycobacterial cell walls. AB - The long-posed question of the nature of the link between the mycolylarabinogalactan and the underlying peptidoglycan of the cell walls of Mycobacterium sp. has been addressed. The insoluble cell wall matrix of Mycobacterium leprae, Mycobacterium tuberculosis, and Mycobacterium bovis was partially hydrolyzed with acid either before or after per-O-methylation and the resulting oligosaccharides further derivatized and analyzed by gas chromatography/mass spectrometry. The structures of fragments arising from the reducing end of arabinogalactan demonstrated the existence of the terminal sequence----5)-D-Galf-(1----4)-L-Rhap-(1---3)-D-GlcNAc. Other analyses confirmed the presence of muramyl-6-P within the peptidoglycan of these mycobacteria. Based on the acid lability of the 3-linked GlcNAc unit, the presence of about equimolar amounts of Rhap-(1----3)-D-GlcNAc and muramyl-6-P in an isolated cell wall fragment, and 31P NMR analysis, it was concluded that the GlcNAc residue of the terminal triglycosyl unit of arabinogalactan is joined by 1-O-phosphoryl linkage to the 6-position of some muramyl residues within the peptidoglycan. Thus, it is reasoned that the massive mycolylarabinogalactan of mycobacteria, responsible for aspects of disease pathogenesis and much of the antibody response in infections, is attached to the peptidoglycan framework by the actinomycete-specific diglycosylphosphoryl bridge, L-Rhap-(1----3)-D-GlcNAc-(1----P, perhaps thereby providing a unique target for site-directed chemotherapy of mycobacterial infections. PMID- 2211697 TI - Free amino acid turnover in methanogens measured by 15N NMR spectroscopy. AB - Turnover of the nitrogen moiety from free amino acid pools in two thermophilic methanogens, Methanobacterium thermautotrophicum delta H and Methanococcus thermolithotrophicus SN1, has been monitored with 15N NMR spectroscopy. In cells growing exponentially on 15NH4Cl, glutamate was the major soluble 15N-labeled species in both organisms. When the Mb. thermoautotrophicum cells were harvested, washed, and resuspended into medium containing 14NH4Cl, the resonance for [15N]glutamate decreased with a half-life of 0.5 h. This is considerably faster than the turnover rate for the carbon side chain of glutamate (7 h) obtained when a 13CO2 pulse followed by a 12CO2 chase was incorporated into the 15N/14N labeling experiment. Such behavior is consistent with recycling of the glutamate carbon skeleton via alpha-ketoglutarate after transamination reactions remove the 15N for biosynthesis of other amino acids, nucleic acids, etc. When the cells were in stationary phase, 15N turnover was considerably slower indicating that transaminase activity had also decreased. Mc. thermolithotrophicus has a much more fragile cell wall and easily lyses. To avoid cell loss in the 15N/14N experiment, 15NH+4 growth followed by 14NH4+ dilution was used. In this organism the glutamate-labeled nitrogen turns over quite rapidly (t1/2 approximately 9 min), at a rate comparable to that for the carbon skeleton (t1/2 approximately 10 min). Beta-Glutamate, the second major carbon and nitrogen pool in this organism, turns over its 15N label very slowly. Therefore, this beta-amino acid does not appear to serve as a nitrogen donor in Mc. thermolithotrophicus. PMID- 2211698 TI - Escherichia coli formate-hydrogen lyase. Purification and properties of the selenium-dependent formate dehydrogenase component. AB - The formate-hydrogen lyase complex of Escherichia coli decomposes formic acid to hydrogen and carbon dioxide under anaerobic conditions in the absence of exogenous electron acceptors. The complex consists of two separable enzymatic activities: a formate dehydrogenase and a hydrogenase. The formate dehydrogenase component (FDHH) of the formate-hydrogen lyase complex was purified to near homogeneity in two column chromatographic steps. The purified enzyme was composed of a single polypeptide of molecular weight 80,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Metal analysis showed each mole of enzyme contained 3.3 g atoms of iron. Denaturation of FDHH released a compound which, when oxidized, displayed a fluorescence spectrum similar to that of the molybdopterin cofactor found in certain other enzymes. The enzyme contained selenium in the form of selenocysteine as determined by radioactive labeling of the enzyme with 75Se and amino acid analysis. FDHH activity was maximal between pH 7.5 and 8.5; however, the enzyme was maximally stable at pH 5.3-6.4 and highly unstable above pH 7.5. Nitrate and nitrite salts caused a drastic reduction in activity. Although azide inhibited FDHH activity, it also protected the enzyme from inactivation by oxygen. PMID- 2211699 TI - Structure of the gene for rat nucleolar protein B23. AB - Protein B23 is an abundant RNA-associated nucleolar phosphoprotein involved in the ribosome assembly process. Previous studies showed that two forms of the protein (B23.1 and B23.2) are generated from a single gene via alternative splicing of 3' exons at the mRNA level (Chang, J. H., and Olson, M. O. J. (1989) J. Biol. Chem. 264, 11732-11737). We now report the structure of the complete B23 gene which spans 11-kilobases of DNA and contains 12 exons coding for the 294 amino acid residues. B23.1 mRNA is encoded by exons 1-9, 11, and 12, whereas exons 1-10 code for the B23.2 mRNA. Each exon codes for a relatively short segment of the protein (2-40 amino acid residues). The exons, which are distributed unevenly over the length of the gene, are separated by introns varying in size between 122 base pairs and 2.2 kilobases. Southern blot analyses using a probe derived from the untranslated segment of exon 10 suggests that a single expressed gene is present in the rat genome. Additional genomic clones contained apparent processed pseudogenes for protein B23. Primer extension studies and comparison with a processed pseudogene reveal a probable transcription initiation site at position -96 from the first ATG. The 5' region of the gene contains several possible regulatory elements. Three GC boxes which are potential binding sites for transcription factor Sp1 were found, including one within the first intron. A segment of about 1500 base pairs in the 5' region is unusually rich in the dinucleotide CpG. Although no CCAAT box was found a well defined TATA box is present at position -126. The latter feature suggests that the B23 gene has some properties of tissue-specific genes in addition to the predominant characteristics of housekeeping genes. PMID- 2211700 TI - Structure of a dermatan sulfate hexasaccharide that binds to heparin cofactor II with high affinity. AB - Dermatan sulfate increases the rate of inhibition of thrombin by heparin cofactor II (HCII) approximately 1000-fold by providing a catalytic template to which both the inhibitor and the protease bind. Dermatan sulfate is a linear polymer of D glucuronic acid (GlcA) or L-iduronic acid (IdoA) alternating with N-acetyl-D galactosamine (GalNAc) residues. Heterogeneity in dermatan sulfate results from varying degrees of O-sulfation and from the presence of the two types of uronic acid residues. To characterize the HCII-binding site in dermatan sulfate, we isolated the smallest fragment of dermatan sulfate that bound to HCII with high affinity. Dermatan sulfate was partially N-deacetylated by hydrazinolysis, cleaved with nitrous acid at pH 4, and reduced with [3H]NaBH4. The resulting fragments, containing an even number of monosaccharide units with the reducing terminal GalNAc converted to [3H]2,5-anhydro-D-talitol (ATalR), were size fractionated and then chromatographed on an HCII-Sepharose column. The smallest HCII-binding fragments were hexasaccharides, of which approximately 6% bound. Based on ion-exchange chromatography, the bound material appeared to comprise a heterogeneous mixture of molecules possessing four, five, or six sulfate groups per hexasaccharide. Subsequently, hexasaccharides with the highest affinity for HCII were isolated by overloading the HCII-Sepharose column. The high-affinity hexasaccharides were fractionated by strong anion-exchange chromatography, and one major peak representing approximately 2% of the starting hexasaccharides was isolated. The high-affinity hexasaccharide was cleaved to disaccharides that were analyzed by anion-exchange chromatography, paper electrophoresis, and paper chromatography. A single disulfated disaccharide, IdoA(2-SO4)----ATalR(4-SO4) was observed, indicating that the hexasaccharide has the following structure: IdoA(2 SO4)----GalNAc(4-SO4)----IdoA(2-SO4)---- GalNAc(4-SO4)----IdoA(2-SO4)----ATalR(4 SO4). Since IdoA(2-SO4)----GalNAc(4-SO4) comprises only approximately 5% of the disaccharides present in intact dermatan sulfate, clustering of these disaccharides must occur during biosynthesis to form the high-affinity binding site for HCII. PMID- 2211701 TI - Methotrexate transport in variant human CCRF-CEM leukemia cells with elevated levels of the reduced folate carrier. Selective effect on carrier-mediated transport of physiological concentrations of reduced folates. AB - This study reports the isolation and characterization of a variant of the human CCRF-CEM leukemia cell line that overproduces the carrier protein responsible for the uptake of reduced folates and the folate analogue methotrexate. The variant was obtained by adapting CCRF-CEM cells for prolonged times to stepwise decreasing concentrations of 5-formyltetrahydrofolate as the sole folate source in the cell culture medium. From cells that were grown on less than 1 nM 5-formyl tetrahydrofolate, a variant (CEM-7A) was isolated exhibiting a 95-fold increased Vmax for [3H]methotrexate influx compared to parental CCRF-CEM cells. The values for influx Km, efflux t0.5, and Ki for inhibition by other folate (analogue) compounds were unchanged. Affinity labeling of the carrier with an N hydroxysuccinimide ester of [3H]methotrexate demonstrate an approximately 30-fold increased incorporation of [3H] methotrexate in CEM-7A cells. This suggests that the up-regulation of [3H]methotrexate influx is not only due to an increased amount of carrier protein, but also to an increased rate of carrier translocation or an improved cooperativity between carrier protein molecules. Incubation for 1 h at 37 degrees C of CEM-7A cells with a concentration of 5 formyltetrahydrofolate or 5-methyltetrahydrofolate in the physiological range (25 nM) resulted in a 7-fold decline in [3H]methotrexate influx. This down-regulation during incubations with 5-formyltetrahydrofolate or 5-methyltetrahydrofolate could be prevented by either the addition of 10-25 nM of the lipophilic antifolate trimetrexate or by preincubating CEM-7A cells with 25 nM methotrexate. The down-regulatory effect was specifically induced by reduced folates since incubation of CEM-7A cells with 25 nM of either methotrexate, 10-ethyl-10 deazaaminopterin, aminopterin, or folic acid, or a mixture of purines and thymidine, had no effect on [3H]methotrexate influx. Similarly, these down regulatory effects on [3H]methotrexate transport by 5-formyltetrahydrofolate, and its reversal by trimetrexate or methotrexate, were also observed, though to a lower extent, for parental CCRF-CEM cells grown in folate-depleted medium rather than in standard medium containing high folate concentrations. These results indicate that mediation of reduced folate/methotrexate transport can occur at reduced folate concentrations in the physiological range, and suggest that the intracellular folate content may be a critical determinant in the regulation of methotrexate transport. PMID- 2211702 TI - The selective inhibition of thrombin by peptides of boroarginine. AB - Peptides containing alpha-aminoboronic acids with neutral side chains are highly effective reaction intermediate analog inhibitors of the serine proteases leukocyte elastase, pancreatic elastase, and chymotrypsin. A protocol has been developed for the synthesis of peptides containing alpha-aminoboronic acids with a basic, 3-guanidinopropyl side chain (boroArg) to extend the range of these compounds to trypsin-like proteases. Ac-(D)Phe-Pro-boroArg-OH, Boc-(D)Phe-Pro boroArg-OH, and H-(D)Phe-Pro-boroArg-OH were prepared as inhibitors of thrombin based on earlier observations that it has a high affinity for this sequence. All three boronic acids are highly effective, slow-binding inhibitors of thrombin, inhibiting it with final inhibition constants and association rates of: 41 pM, 5.5 x 10(6) M-1 s-1; 3.6 pM, 9.3 x 10(6) M-1 s-1; less than 1 pM, 8.0 x 10(6) M-1 s-1, respectively. Comparison of their binding at equilibrium to thrombin, plasma kallikrein, factor Xa, plasmin, and two-chain tissue plasminogen activator has shown that all three inhibitors have at least 2 orders of magnitude greater affinity for thrombin, with the exception of the acetyl derivative which has a 40 fold greater affinity for thrombin than kallikrein. The boroarginine peptides are effective in inhibiting the action of thrombin in rabbit plasma against its physiological substrates. Activated partial thromboplastin time was significantly prolonged in vitro by all of the inhibitors at concentrations of 50-200 nM. Prolongations of activated partial thromboplastin time were also observed in rabbits after intravenous (40-80 micrograms/kg or subcutaneous (0.20-2 mg/kg) injections of Ac-(D)Phe-Pro-boroArg-OH. Results indicate that this new class of synthetic thrombin inhibitors may be clinically useful as antithrombotic agents. PMID- 2211703 TI - Properties of overexpressed phage T5 D15 exonuclease. Similarities with Escherichia coli DNA polymerase I 5'-3' exonuclease. AB - The D15 gene of the bacteriophage T5, thought to encode an exonuclease, was cloned into an M13 phage on a 1344-base pair fragment. The deduced amino acid sequence of 291 residues (Kaliman, A. V., Krutilina, A. I., Kryukov, V. M., and Bayev, A. A. (1986) FEBS Lett. 195, 61-64) shows a high degree of homology with the first 320 amino acid residues of Escherichia coli DNA polymerase I, the region containing the enzyme's 5'-3' exonuclease activity. Recombinant M13 phage DNA was manipulated by oligonucleotide-directed mutagenesis to enable subcloning into a high efficiency expression vector, allowing the production of large amounts of enzyme for physical characterization and crystallization trials. The enzyme was purified to homogeneity. The purified enzyme is active on both native and heat-denatured DNA and shows no endonuclease activity on either double stranded closed-circular or nicked DNA. The enzyme is also able to degrade some oligonucleotides in a manner which depends not only on the nucleotide sequence but also on the state of hybridization of the potential substrate. The mode of action of this enzyme is similar to, although not identical to that of the 5'-3' exonuclease activity of E. coli DNA polymerase I. PMID- 2211704 TI - Post-translational modification of a monocyte-specific chemoattractant synthesized by glioma, osteosarcoma, and vascular smooth muscle cells. AB - Chemotaxis is an important step in monocyte recruitment in inflammation, wound healing, and tumor growth. We reported previously that monocyte chemotactic activity secreted by malignant cells and normal smooth muscle cells is associated with a protein or family of proteins that are related to the monocyte-specific smooth muscle cell-derived chemotactic factor (SMC-CF) (Graves, D. T., Jiang, Y. L., Williamson, M. J., and Valente, A. J. (1989) Science 245, 1490-1493). Similar monocyte chemotactic proteins (MCP-1) produced by U-105MG human glioma cells have also been identified (Yoshimura, T., Robinson, E. A., Tanaka, S., Appella, E., Kuratsu, J., and Leonard, E. J. (1989) J. Exp. Med. 169, 1449-1459). We now report that the MCP-1 gene is expressed in MG-63 human osteosarcoma and vascular smooth muscle cells and that SMC-CF antiserum specifically immunoprecipitates proteins synthesized by U-105MG glioma cells. Experiments were undertaken to elucidate the processing pathway of MCP-1/SMC-CF-like proteins in each of these cell types. These experiments demonstrate that larger MCP-1/SMC-CF-like proteins are derived from a Mr = 9000 precursor. Post-translational modification involves the addition of O-linked carbohydrates and sialic acid residues. Differences in carbohydrate processing account for the heterogeneity in MCP-1/SMC-CF-like proteins produced by different cell types. Secretion of these proteins occurs rapidly following processing events in the endoplasmic reticulum-Golgi compartment. PMID- 2211705 TI - Evidence that only newly made phosphatidylethanolamine is methylated to phosphatidylcholine and that phosphatidylethanolamine is not significantly deacylated-reacylated in rat hepatocytes. AB - The metabolism of the molecular species of phosphatidylethanolamine derived from [3H]ethanolamine and molecular species of phosphatidylcholine derived from [3H]ethanolamine or [methyl-3H]choline has been studied in rat hepatocytes. After an initial pulse of radioactivity for 1 h and a chase for up to 24 h, the cells were harvested and the incorporation of label into the various molecular species of phosphatidylethanolamine and phosphatidylcholine was determined. The incorporation and metabolism of choline- and ethanolamine-labeled phosphatidylcholine was consistent with deacylation of some species of phosphatidylcholine and reacylation to form molecular species of phosphatidylcholine with different fatty acyl components. In contrast, such remodeling of ethanolamine-labeled phosphatidylethanolamine was not evident. Radioactivity disappeared from all molecular species of phosphatidylethanolamine without an increase in any of the species of phosphatidylethanolamine. This radioactivity was recovered in water-soluble metabolites in the cells and medium. Phosphatidylethanolamine (16:0-22:6) had an initial turnover rate (5.8 nmol/h) which was two or more times that of any of the other major molecular species of phosphatidylethanolamine. The molecular species of phosphatidylethanolamine displayed biphasic turnover profiles. The second rate of decay of radioactivity between 12 and 24 h was 2-4 times slower than the initial decay rate. During the first 2 h of the chase period, phosphatidylcholine was a major metabolite of labeled phosphatidylethanolamine. Subsequently, there was minimal conversion of phosphatidylethanolamine to phosphatidylcholine which suggests that only newly made phosphatidylethanolamine is available as a substrate for methylation to phosphatidylcholine. PMID- 2211706 TI - Evidence for conservation of ferritin sequences among plants and animals and for a transit peptide in soybean. AB - Ferritin is a large multisubunit protein that stores iron in plants, animals, and bacteria. In animals, the protein is mainly cytoplasmic and is highly conserved, while in plants ferritin is found in chloroplasts and other plastids. Ferritin is synthesized in plants as a larger precursor of the mature subunit. There is no sequence information for ferritin from plants, except an NH2-terminal peptide of 35 residues which shows little similarity to any known ferritin sequences or transit peptides (Laulhere, J. P., Laboure, A. M., and Briat, J. F. (1989) J. Biol. Chem. 264, 3629-3635). To understand the genetic origin and the location of ferritin synthesis in plant cells, as well as the structure of ferritin from plants, we have sequenced both CNBr peptides from pea seed ferritin and nucleotides of a soybean hypocotyl ferritin cDNA, identified using a frog ferritin cDNA as a probe. Comparison of pea and soybean sequences showed an identity of 89%. Alignment of the plant ferritin sequences with animal ferritins showed 55-65% sequence identity in the common regions. However, a peptide of 28 amino acids extended the NH2 terminus of the plant ferritins. Furthermore, the cDNA encoded additional amino acids which appear to be a transit peptide. None of the sequences in soybean ferritin were found in the tobacco chloroplast genome, suggesting, as does the transit peptide, a nuclear location of ferritin gene(s) in plants. Plant ferritin mRNA is 400-500 nucleotides longer than animal ferritin mRNAs, a difference accounted for in part by the extra peptides encoded. The size of soybean ferritin mRNA was constant in different tissues but expression varied in different tissues (leaf greater than hypocotyl). Thus, higher plants and animal ferritins display sequence homology and differential tissue expression. An ancient, common progenitor apparently gave rise to contemporary eukaryotic ferritins after specific modifications, e.g. transport to plasmids. PMID- 2211707 TI - Distinctive structure and function of human apolipoprotein variant ApoA-IV-2. AB - We have investigated the molecular structure, phospholipid binding, and lecithin cholesterol acyltransferase catalytic activity of pure apoA-IV-2, a basic variant isoform of apoA-IV which is inherited as a classical Mendelian allele with a gene frequency of 0.09. Circular dichroism spectroscopy established that the alpha helical content of apoA-IV-2 was 75% in the native state (versus 56% for apoA-IV 1), and increased to 88% in the presence of phospholipid. Fluorescence titration established that apoA-IV-2 bound to egg phospholipid vesicles with a Ka of 3.3 x 10(6) liter/mol, 2.4-fold greater than the affinity of apoA-IV-1. Fluorescence quenching studies revealed that, unlike apoA-IV-1, binding of apoA-IV-2 to phospholipid vesicles induced strong shielding of the amino-terminal tryptophan against iodide quenching. Enzyme kinetic studies using both saturated and unsaturated phospholipid substrates demonstrated that apoA-IV-2 was 36-71% more efficient in activating lecithin-cholesterol acyltransferase than apoA-IV-1. We conclude that apoA-IV-2 has more alpha-helical structure, is more stable in solution, and is more hydrophobic than apoA-IV-1, and that these distinctive structural features are associated with a higher affinity for phospholipid surfaces and an increased catalytic efficiency of lecithin:cholesterol acyltransferase activation. The biophysical basis for this latter characteristic may be the ability of apoA-IV-2 to penetrate phospholipid surfaces to a greater depth than apoA-IV-1. These molecular properties may be responsible for the increased levels of high density lipoproteins which have been observed in apoA-IV 2 heterozygotes. PMID- 2211708 TI - Distinct properties of Escherichia coli products of plant-type ribulose-1,5 bisphosphate carboxylase/oxygenase directed by two sets of genes from the photosynthetic bacterium Chromatium vinosum. AB - We have recently described the existence of two sets of genes encoding ribulose 1,5-bisphosphate carboxylase/oxygenase (Rbu-P2 carboxylase), rbcA-rbcB and rbcL rbcS, in the photosynthetic purple sulfur bacterium Chromatium vinosum (Viale, A.M., Kobayashi, H., and Akazawa, T. (1989) J. Bacteriol. 171, 2391-2400). These genes were cloned in plasmid vectors, and their expression was studied in Escherichia coli. Expression of rbcA-rbcB in E. coli was obtained under the control of its own promoter. On the other hand, expression of rbcL-rbcS in this host was not observed unless these genes were cloned under the control of the tac promoter. Purified rbcA-rbcB and rbcL-rbcS products from E. coli consisted of large and small subunits in equimolar ratios. They also showed very close elution profiles to Rbu-P2 carboxylase isolated from C. vinosum in size-exclusion chromatography columns, thus suggesting hexadecameric (L8S8) structures. Vmax of Rbu-P2 carboxylase were very similar for both enzymes, but the Km values for CO2 and ribulose 1,5-bisphosphate showed some differences. Immunochemical and N terminal amino acid sequence analyses of the large and small subunits encoded by rbcA-rbcB and rbcL-rbcS also differed, especially at the level of the small subunits. The comparisons described above as well as the analysis of C. vinosum crude extracts by anion-exchange chromatography indicated that Rbu-P2 carboxylase encoded by rbcA-rbcB was the only species detected in the photosynthetic bacterium. PMID- 2211709 TI - An immune complex selective affinity matrix utilizing a synthetic peptide. AB - A synthetic peptide possessing an amino acid sequence patterned on the globular head region of human complement component 1 subcomponent q (C1q) was tested for immunoglobulin binding. The peptide designated complementary binding peptide 2 (CBP2) was able to inhibit Staphylococcus aureus Protein A and human C1q from binding rabbit immunoglobulin at peptide concentrations for 50% inhibition of 1 and 10 microM, respectively. When attached to a solid-phase matrix in a column, CBP2 was able to bind immune complexes consisting of horseradish peroxidase plus rabbit antiperoxidase antibody or alkali-aggregated human immunoglobulins. A 1:4 mixture of immune complex to free immunoglobulin when passed over the CBP2 column demonstrated selective immune complex binding. Further controls established that CBP2 was in fact binding the immunoglobulin component of the immune complexes in a reversible fashion. The immune complex specificity of the column suggested a functional affinity was forming when CBP2 interacted with immune complexes. The possibility that the sequence of CBP2 is part of the immunoglobulin binding site of human C1q is discussed. PMID- 2211710 TI - Modification of triantennary glycopeptide into probes for the asialoglycoprotein receptor of hepatocytes. AB - Triantennary glycopeptide was oxidized with galactose oxidase to convert the CH2OH group on terminal galactose residues to the aldehyde group (oxo-form). Kinetic profiling by reverse phase high performance liquid chromatography allowed termination of the reaction when intermediate mono-oxo- and di-oxo-triantennary glycopeptides had been produced. The mixture of the oxo-glycopeptides was derivatized with 2,4-dinitrophenylhydrazine for efficient separation, and each isomeric triantennary hydrazone was separated by reverse phase high performance liquid chromatography. The purified hydrazones were reverted to three original isomeric mono-oxo- and di-oxo-glycopeptides, and a single tri-oxo-glycopeptide. Each of these isomers was characterized by proton NMR by a downfield shift in the anomeric signals of 6-oxo-Gal residue(s). The functionalized glycopeptides were successively modified with dansyl and naphthyl groups through the 6-oxo-Gal residue and the amino terminus of the peptide to prepare three isomeric glycopeptide probes suitable for conformation studies by fluorescence energy transfer measurements. Alternatively, glycopeptides were derivatized by attaching t-butyloxycarbonyl-L-tyrosine to the amino terminus of the peptide, and reductive amination of the 6-oxo-Gal residue, provided three isomeric triantennary photoaffinity probes which allow photolyzable groups to be attached to the newly introduced 6-amino-Gal residue. PMID- 2211711 TI - Defined geometry of binding between triantennary glycopeptide and the asialoglycoprotein receptor of rat heptocytes. AB - Three derivatives of a triantennary glycopeptide, each containing a single uniquely located 6-amino-galactose residue at either position 6', 6, or 8, were modified at the 6-amino group by attachment of a photolyzable reagent and radiolabeled by iodination of tyrosine. These were allowed to bind to the asialoglycoprotein receptor of isolated rat hepatocytes and photolyzed for affinity labeling. (formula; see text) Each probe specifically labeled either the major (RHL1) or minor (RHL2/3) subunits which comprise the receptor. A photolyzable group attached to galactose residue 6 6' specifically radiolabeled RHL1, whereas a photolyzable group attached to galactose 8 specifically labeled RHL2/3. Photoaffinity labeling of a soluble rat hepatic lectin preparation demonstrated that the minor subunits (RHL2/3) were no longer labeled by the triantennary probe with a photolyzable group at galactose 8. The inhibitory potency of a variety of complex glycopeptides against radiolabeled ligand binding to both rat hepatocytes and soluble lectin are in agreement with photoaffinity results that galactose 8 of triantennary glycopeptide is of unique importance by binding solely to the minor subunits (RHL2/3) of the asialoglycoprotein receptor on hepatocytes. Conversely, galactose residues 6 and 6' bind specifically to the major subunit (RHL1), indicating a precise binding geometry between the trivalent ligand and lectin. PMID- 2211712 TI - Nutritional regulation and tissue-specific expression of the malic enzyme gene in the chicken. Transcriptional control and chromatin structure. AB - Refeeding starved chicks causes a 25- to 50-fold increase in the level of malic enzyme mRNA in liver. To define the regulated steps, we measured transcriptional activity of the malic enzyme gene using the nuclear run-on assay and a variety of DNA probes specific to the malic enzyme gene. Refeeding starved chicks stimulated transcription of the malic enzyme gene in liver by 40- to 50-fold. An increased transcription rate was detectable at 1.5 h, was maximal at 3 h, and remained high at 24 h of refeeding. The level of nuclear precursor RNA for malic enzyme assessed by hybridization with intron-specific probes was high in liver of refed birds, and barely detectable in that of starved birds. These results indicate that nutritional regulation of the level of malic enzyme mRNA is transcriptional. Low levels of malic enzyme mRNA in brain, kidney, and heart correlated well with low rates of transcription of the malic enzyme gene in these tissues. In contrast to liver, neither the rate of transcription nor the steady-state level of malic enzyme mRNA was affected by refeeding starved birds. A series of DNase I hypersensitive sites were located within 4000 base pairs upstream of the transcription start site of the malic enzyme gene in liver. The DNase I hypersensitive region extending from the start of transcription to 400 base pairs upstream was much more pronounced in the refed state than in the starved state. This change in DNase I hypersensitivity followed the same time course as increased transcription of the malic enzyme gene. This DNase I-hypersensitive region also was present at low intensity in kidney and heart independently of nutritional state. The three constitutive DNase I-hypersensitive sites further upstream were present in liver but not in kidney or heart. PMID- 2211713 TI - Solubilization and biochemical characterization of the high affinity [3H]ryanodine receptor from rabbit brain membranes. AB - A high affinity [3H]ryanodine receptor has been solubilized from rabbit brain membranes and biochemically characterized. [3H]Ryanodine binding to rabbit brain membranes is specific and saturable, with a Kd of 1.3 nM. [3H]Ryanodine binding is enriched in membranes from the hippocampus but is significantly lower in membranes from the brain stem and spinal cord. Approximately 60% of [3H]ryanodine labeled receptor is solubilized from brain membranes using 2.5% CHAPS and 10 mg/ml phosphatidylcholine containing 1 M NaCl. The solubilized brain [3H]ryanodine receptor sediments through sucrose gradients like the skeletal receptor as a large (approximately 30 S) complex. Solubilized receptor is specifically immunoprecipitated by sheep polyclonal antibodies against purified skeletal muscle ryanodine receptor coupled to protein A-Sepharose. [3H]Ryanodine labeled receptor binds to heparin-agarose, and a protein of approximately 400,000 Da, which is cross-reactive with two polyclonal antibodies raised against the skeletal muscle ryanodine receptor, elutes from the column and is enriched in peak [3H]ryanodine binding fractions. These results suggest that the approximately 400,000-Da protein is the brain form of the high affinity ryanodine receptor and that it shares several properties with the skeletal ryanodine receptor including a large oligomeric structure composed of approximately 400,000 Da subunits. PMID- 2211714 TI - Identification of the active site tyrosine of Flp recombinase. Possible relevance of its location to the mechanism of recombination. AB - A combination of site-directed mutagenesis and amino acid sequence analysis identifies Tyr-343 of Flp recombinase as the residue that covalently attaches to DNA during the strand-cleavage step of recombination. This residue is part of the invariant His-Arg-Tyr triad of the Int family of recombinases. Tyr-343 is located in a highly protease-accessible (and hence "open") region of Flp. This placement may provide the conformational flexibility required for the dual role of Tyr-343 in recombination: nicking of the DNA strands to initiate recombination and joining of the nicked strands across partner substrates to complete recombination. In-frame insertion of a few amino acids close to Tyr-343 (and to its amino-terminal side) does not affect substrate recognition by Flp but abolishes its catalytic function. PMID- 2211715 TI - A bacteriophage P1-encoded modulator protein affects the P1 c1 repression system. AB - Bacteriophage P1 encodes a tripartite immunity system composed of the immC, immI, and immT region. Their basic genetic elements are the c1 repressor of lytic functions, the c4 repressor which negatively regulates antirepressor synthesis, and the bof gene, respectively. The function of the latter will be described here. We have cloned and sequenced the bof gene from P1 wild type and a P1 bof amber mutant. Based on the position of a TAG codon of the bof amber mutant the bof wild type gene was localized. It starts with a TTG codon, comprises 82 codons, and is preceded by a promoter structure. The bof protein (Mr = 7500) was overproduced in Escherichia coli from a bof recombinant plasmid and was purified to near homogeneity. The N-terminal amino acids predicted from the DNA sequence of the bof gene were confirmed by sequence analysis of the bof protein. Using a DNA mobility shift assay, we show that bof protein enhances the binding of c1 repressor to the operator of the c1 gene. In accordance with this result, in transformants of Escherichia coli, containing both a bof- and a c1-encoding plasmid, c1 expression is down-regulated. We conclude that bof acts as a modulator protein in the repression of a multitude of c1-controlled operators in the P1 genome. PMID- 2211716 TI - Cation-dependent changes in the binding specificity of the platelet receptor GPIIb/IIIa. AB - The presence of manganese (Mn2+) significantly increases the binding of the platelet surface receptor GPIIb/IIIa to two synthetic peptides Gly-Arg-Gly-Asp Ser-Pro (GRGDSP) and Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val (L10) that contain the recognition sequences RGD and KQAGDV, respectively. This results in an increase in the amount of GPIIb/IIIa adsorbed by GRGDSPK- and L10-Sepharose by 12 20-fold. Additionally, Mn2+ eliminates contaminating platelet vitronectin receptor, alpha v beta 3, which copurifies with GPIIb/IIIa on the peptide affinity columns in the absence of Mn2+. In contrast to this increased peptide binding of GPIIb/IIIa, Mn2+ reduces the binding of GPIIb/IIIa to its macromolecular RGD-containing ligands fibrinogen, fibronectin, and vitronectin. These results could mean that Mn2+ changes the structure of the binding site on GPIIb/IIIa such that it is now better suited to accommodate conformations available to the RGD sequence within short, linear synthetic peptides but not available to the RGD sequences within the natural ligands. To support this hypothesis we tested a conformationally restricted cyclic peptide, cyclic 2,10 GPenGHRGDLRCA, which in competition assays, preferentially inhibits the binding of GPIIb/IIIa to fibrinogen but does not inhibit well the binding of other RGD dependent integrins, alpha v beta 3 and alpha 5 beta 1 to their respective ligands. In such assays, the presence of Mn2+ dramatically changed the binding specificity of GPIIb/IIIa by shifting the preference of the receptor away from the selective peptide, cyclic 2,10-GPen-GHRGDLRCA toward the nonselective GRGDSP peptide. This shift parallels the Mn2(+)-dependent change of the binding of GPIIb/IIIa to its natural protein ligands. PMID- 2211717 TI - Identification and characterization of LAMP-1 as an activation-dependent platelet surface glycoprotein. AB - Platelets normally circulate in a quiescent state. When activated, they undergo biochemical and morphological changes which greatly alter their function and contribute to their role in thrombosis and hemostasis. We have identified, cloned, and sequenced a cDNA from a human unbilical vein endothelial cell library that encodes a 110-kDa integral membrane protein. This protein is present on the surface of activated but not resting platelets and has previously been identified as lysosomal-associated membrane protein 1 (LAMP-1). Half-maximal surface expression of platelet LAMP-1 was induced by concentrations of thrombin that resulted in lysosome enzyme release, not alpha-, or dense granule release. Also consistent with lysosome enzyme studies, there was little surface expression of LAMP-1 in response to the weak agonists ADP and epinephrine. In addition, sucrose density gradient fractionation of platelet granules showed colocalization of LAMP 1 with the lysosomal enzyme, beta-galactosidase, and not with markers of alpha- or dense granules. While we found virtually no LAMP-1 on the resting platelet surface (0-90 molecules/cell), we estimated a mean of 1175 LAMP-1 molecules on the thrombin-activated platelet surface. The translocation of this heavily glycosylated protein to the platelet surface upon stimulation may play a role in the adhesive, prothrombic nature of these cells. PMID- 2211718 TI - A far upstream element stimulates c-myc expression in undifferentiated leukemia cells. AB - A sensitive exonuclease assay revealed multiple sites for interaction, in vitro, of sequence specific factors with c-myc upstream elements. At one site, more than 1500 base pairs upstream of the c-myc promoter P1, binding activity was lost as dimethyl sulfoxide (Me2SO) induced shut-off of c-myc expression in HL-60 and U 937 leukemia cells. The disappearance of other specific binding activities was not noted. In addition, the binding activity was noted to be cell-line specific. The sequence binding the Me2SO-regulated factor was precisely located allowing confirmation of the temporal pattern of regulation by electrophoretic mobility shift analysis. Because the binding activity was most abundant before the decrease of c-myc expression during differentiation, it was inferred that the far upstream element (FUSE) served a positive role, potentiating c-myc expression. A 4-base pair deletion which eliminated binding to FUSE also reduced expression of a transfected, chimeric c-myc-CAT gene in untreated, but not in Me2SO-treated U 937 cells. FUSE and its binding protein may contribute to cell line- and differentiation-specific modes of c-myc regulation. PMID- 2211719 TI - Inhibition by 6-fluoromevalonate demonstrates that mevalonate or one of the mevalonate phosphates is necessary for lymphocyte proliferation. AB - The sterol synthesis inhibitor 6-fluoromevalonate (Fmev) was used to explore the role of mevalonate products in lymphocyte proliferation. Fmev blocks the synthesis of isopentenyl pyrophosphate and all more distal products in the sterol pathway. When cells were cultured in lipoprotein-deficient medium, Fmev (200 microM) completely inhibited mitogen-stimulated human lymphocyte proliferation, quantified by measuring DNA synthesis. The addition of low density lipoprotein (LDL) restored lymphocyte responses to normal, whereas mevalonate was totally ineffective. Similar results were obtained with concentrations of Fmev up to 1 mM. These results contrast with those observed when sterol biosynthesis was blocked with lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. When lymphocyte proliferation was blocked with lovastatin (5 microM), either high concentrations of mevalonate or LDL together with low concentrations of mevalonate was required to restore responses. In contrast, neither LDL nor low concentrations of mevalonate when alone was able to restore lymphocyte DNA synthesis in cultures blocked with 5 microM lovastatin. The effect of Fmev on the capacity of exogenous mevalonate to restore proliferation of lovastatin-blocked lymphocytes was directly examined. Fmev had no effect on the capacity of LDL plus low concentrations of mevalonate to restore DNA synthesis to lovastatin-blocked lymphocytes, indicating that the synthesis of the necessary factor from mevalonate was unaltered by Fmev. Fmev profoundly blocked lymphocyte endogenous sterol synthesis, decreasing incorporation of radiolabeled acetate into digitonin precipitable sterols by up to 98%. LDL did not alter the capacity of Fmev to block sterol synthesis. The possibility that Fmev allowed shunting of endogenous mevalonate into essential lipid products was assessed by examining the incorporation of radiolabeled mevalonate. Fmev (200 microM) inhibited the incorporation of mevalonate into all lipids, including ubiquinone, dolichol, and other non-sterol lipids by up to 98%, and this was not altered by LDL. Furthermore, Fmev (200 microM) suppressed the incorporation of radiolabeled mevalonate into protein by up to 97%. These data confirm that a product of mevalonate is essential for cell proliferation. However, the results indicate that the required product is directly synthesized from mevalonate or mevalonate phosphates rather than from a more distal isoprenoid metabolite. PMID- 2211721 TI - Differential expression and distinct structure of 69- and 100-kDa forms of 2-5A synthetase in human cells treated with interferon. AB - Using specific monoclonal and polyclonal antibodies, the induction, synthesis and subcellular localization of 69- and 100-kDa forms of 2',5'-oligoadenylate (2-5A) synthetase (p69 and p100) were investigated in alpha-interferon-treated human HeLa and Daudi cells. Although both p69 and p100 were induced by interferon, there were significant differences in the interferon dose-response and the kinetics of synthesis of each protein in these cell lines. Both proteins are localized mainly in the cytoplasm. However, immunoenzymatic staining analysis of interferon-treated cells indicated that a proportion of p69 is concentrated around the nuclei and the rest is distributed in a specific pattern in the cytoplasm whereas p100 is found in a diffuse state in the cytoplasm. In accord with its association to cell membranes, p69 is myristilated. The [35S]cysteine and [3H]myristate-labeled p69 preparations were resolved by two-dimensional gel isoelectric focusing with pI values in the pH range of 7.0-8.0 and 7.0-7.5, respectively. These observations suggested the existence of two forms of p69 which might be complexed together as a dimer. In favor with a dimeric form of p69, in gel filtration experiments the peak of p69 was routinely found in fractions corresponding to a molecular mass of 160 kDa whereas p100 was recovered as a monomer. Taken together, these results indicate that p69 and p100 have distinct characteristics and that their expression is a specific property of each cell type in response to interferon. PMID- 2211720 TI - Calmodulin-binding proteins in the nuclei of quiescent and proliferatively activated rat liver cells. AB - alpha-Spectrin, myosin light chain kinase (MLCK), and caldesmon have been detected in the nuclei of rat liver cells by 125I-calmodulin overlay, immunoblotting, and immunocytochemical methods. alpha-Spectrin is localized in the nuclear matrix, nuclear envelope, and nuclear pores. It has also been detected inside the nuclei in the form of small aggregates. MLCK is present in the nuclear matrix, envelope, nucleoli, and in a nuclease extract (S1 subfraction) but not in the nuclear pores. Caldesmon shows a diffuse distribution pattern inside the nuclei but it is not present in the nucleoli. Since all these proteins are components of the actin-myosin motility systems the presence of actin in the different nuclear subfractions has also been investigated: actin is present in the nuclear matrix, nuclear envelope, nucleoli, and nuclear pores. Proliferative activation of rat liver cells in vivo by partial hepatectomy induces the increase of alpha-spectrin, MLCK, and actin in different nuclear subfractions. This, together with the increase of nuclear calmodulin at the same time after hepatectomy (Pujol, M. J., Soriano, M., Aligue, R., Carafoli, E., and Bachs, O. (1989) J. Biol. Chem. 264, 18863-18865), indicates that nuclear calmodulin could activate a nuclear contractile system during proliferative activation. A 62-kDa protein (p62) which binds to calmodulin columns and shows immunological similarities to caldesmon is specifically located in the region surrounding the nuclear envelope and is associated with the heterochromatin. PMID- 2211722 TI - Characterization of anti-Z-DNA antibody binding sites on Z-DNA by nuclear magnetic resonance spectroscopy. AB - Two monoclonal anti-Z-DNA antibodies, Z22 and Z44, were shown to bind to the oligonucleotides, d(CG)2 and d(CG)3, and to interact with different parts of the helix. 1H nuclear magnetic resonance spectroscopy showed that Fab fragments stabilize an ordered structure in the tetranucleotide d(CG)2. Nuclear Overhauser effects measured in the presence of Z22 Fab indicate a syn conformation of guanine residues of d(CG)2. Intermolecular transfer of saturation between the Fabs and bound d(CG)3 was detected by a saturation of the protein spectrum and observation of changes in the DNA spectrum. Antibodies with deuterated aromatic amino acids were prepared to eliminate the protein aromatic resonances and thereby allow a more detailed analysis of the transfer to the DNA base protons. The greatest transfer with Z44 was to the dC-5 protons although all of the base protons interact with this antibody. Little, if any, transfer to the DNA base protons was observed with Z22. These results are consistent with a Z44 binding site on the convex surface of the Z-helix (analogous to the major groove of B DNA) and a Z22 binding site on the sugar-phosphate backbone. PMID- 2211723 TI - Immunological and structural characterization of a high affinity anti-fluorescein single-chain antibody. AB - Single-chain antibody of the (NH2) VL-linker-VH (COOH) design, was constructed based on prototype high affinity anti-fluorescein monoclonal antibody (mAb) 4-4 20. Purified single-chain antibody (SCA) 4-4-20/212 was studied relative to Ig mAb 4-4-20 in terms of ligand binding, kinetics, idiotypy, metatypy, and stability in denaturing agents. Ligand-binding data correlated with metatypic relatedness of the liganded site. Anti-metatypic reagents reacted preferentially with the liganded conformer of the 4-4-20 antibody active site and were unreactive with free ligand and the non-liganded (idiotypic) state. All results were consistent with the conclusion that SCA 4-4-20/212, with a 14-amino acid linker folded into a native conformational state that closely simulated the prototypical mAb. Furthermore, GndHCl unfolding and refolding studies demonstrated H and L chain variable domain intrinsic stability between SCA 4-4 20/212 and a 50 kDa antigen-binding fragment were nearly identical. This suggested CH1 and CL domain interactions may be more prevalent in V region molecular dynamics than structure. PMID- 2211724 TI - The calcium-binding site of clathrin light chains. AB - Clathrin light chains are calcium-binding proteins (Mooibroek, M. J., Michiel, D. F., and Wang, J. H. (1987) J. Biol. Chem. 262, 25-28) and clathrin assembly can be modulated by calcium in vitro. Thus, intracellular calcium may play a regulatory role in the function of clathrin-coated vesicles. The structural basis for calcium's influence on clathrin-mediated processes has been defined using recombinant deletion mutants and isolated fragments of the light chains. A single calcium-binding site, formed by residues 85-96, is present in both mammalian light chains (LCa and LCb) and in the single yeast light chain. This sequence has structural similarity to the calcium-binding EF-hand loops of calmodulin and related proteins. In mammalian light chains, the calcium-binding sequence is flanked by domains that regulate clathrin assembly and disassembly. PMID- 2211725 TI - Substitution of arginine for glycine at position 847 in the triple-helical domain of the alpha 1 (I) chain of type I collagen produces lethal osteogenesis imperfecta. Molecules that contain one or two abnormal chains differ in stability and secretion. AB - Dermal fibroblasts from a fetus with perinatal lethal OI synthesized normal and abnormal type I procollagen molecules. The abnormal molecules contained one or two pro alpha 1 (I) chains in which glycine at position 847 in the triple helical region was substituted by arginine as the result of a de novo G-to-A transition in the first base of the glycine codon. The substitution resulted in increased posttranslational modification amino-terminal of the mutation site of all chains in molecules that contained one or more abnormal chains. Secretion of the overmodified molecules was impaired, and intracellular retention of molecules which contained two abnormal chains was greater than that of molecules which contained one abnormal chain. The thermal stability of molecules that contained two abnormal chains was markedly lower than that of molecules containing one abnormal chain. After cleavage of molecules with vertebrate collagenase, the thermal stability of the overmodified A fragments was greater than that of the normal molecules. Our findings indicate that the cell distinguishes three classes of molecules and suggest that these molecules differ depending on the number of abnormal chains in the trimer. PMID- 2211726 TI - Protein-protein interactions between adenovirus DNA polymerase and nuclear factor I mediate formation of the DNA replication preinitiation complex. AB - The in vitro adenovirus (Ad) DNA replication system provides an assay to study the interaction of viral and host replication proteins with the DNA template in the formation of the preinitiation complex. This initiation system requires in addition to the origin DNA sequences 1) Ad DNA polymerase (Pol), 2) Ad preterminal protein (pTP), the covalent acceptor for protein-primed DNA replication, and 3) nuclear factor I (NFI), a host cell protein identical to the CCAAT box-binding transcription factor. The interactions of these proteins were studied by coimmunoprecipitation and Ad origin DNA binding assays. The Ad Pol can bind to origin sequences only in the presence of another protein which can be either pTP or NFI. While NFI alone can bind to its origin recognition sequence, pTP does not specifically recognize DNA unless Ad Pol is present. Thus, protein protein interactions are necessary for the targetting of either Ad Pol or pTP to the preinitiation complex. DNA footprinting demonstrated that the Ad DNA site recognized by the pTP.Pol complex was within the first 18 bases at the end of the template which constitutes the minimal origin of replication. Mutagenesis studies have defined the Ad Pol interaction site on NFI between amino acids 68-150, which overlaps the DNA binding and replication activation domain of this factor. A putative zinc finger on the Ad Pol has been mutated to a product that fails to bind the Ad origin sequences but still interacts with pTP. These results indicate that both protein-protein and protein-DNA interactions mediate specific recognition of the replication origin by Ad DNA polymerase. PMID- 2211727 TI - The polymerization and thrombin-binding properties of des-(B beta 1-42)-fibrin. AB - Multiple factors affect the thrombin-catalyzed conversion of fibrinogen to fibrin, including: fibrinopeptide (FPA and FPB) release leading to exposure of two types of polymerization domains ("A" and "B," respectively) in the central portion of the molecule, and exposure of a noncatalytic "secondary" thrombin binding site in fibrin. Fibrinogen containing the FPA sequence but lacking the B beta 1-42 sequence ("des-(B beta 1-42)-fibrinogen"), was compared to native fibrinogen (containing both FPA and FPB) to investigate the role played by B beta 1-42 in the polymerization of alpha-fibrin (i.e. fibrin lacking FPA), to compare reptilase and thrombin cleavage of FPA from fibrinogen, and to explore the location and function of the secondary thrombin-binding site. Electron microscopy of evolving polymer structures (mu, 0.14; pH 7.4) plus turbidity measurements, showed that early thin fibril formation as well as subsequent lateral fibril associations were impaired in des-(B beta 1-42)-alpha-fibrin, thus indicating that the B beta 1-42 sequence contributes to the A polymerization site. Reptilase activated des-(B beta 1-42)-alpha-fibrin polymerized even more slowly than thrombin-activated des-(B beta 1-42)-alpha-fibrin, differences that disappeared when repolymerization of preformed fibrin monomers was carried out. Since existing data indicate that thrombin releases FPA in a concerted manner, resulting in relatively rapid evolution of fully functional divalent alpha-fibrin monomers, it can be inferred that delayed fibrin assembly of reptilase fibrin is due to slower formation of divalent alpha-fibrin monomers. Thrombin-activated des (B beta 1-42)-alpha-fibrin polymerized more rapidly at low ionic strength (mu, 0.04) than did native alpha,beta-fibrin, a reversal of their behavior at physiological ionic strength (mu, 0.14). Concomitant measurement of FPA release revealed modest slowing of release at low ionic strength from des-(B beta 1-42) fibrinogen (t1/2, 36.5 versus 21.5 min) and marked slowing from native fibrinogen (t1/2, 138 versus 22.2 min). This behavior correlated with increased thrombin binding to native alpha,beta-fibrin at low ionic strength, coupled with weak thrombin binding to des-(B beta 1-42)-alpha-fibrin, and indicates that secondary thrombin binding plays an important role in regulating thrombin diffusion and catalytic activity. Des-(B beta 1-42)-fibrinogen lacks or has a markedly defective secondary thrombin-binding site, from which we conclude that the B beta 15-42 sequence in fibrin plays a major role in forming or providing this site. PMID- 2211729 TI - Pyrroline 5-carboxylate dehydrogenase of the mitochondrial matrix of rat liver. Purification, physical and kinetic characteristics. AB - The oxidation of proline to glutamate in mitochondria requires two enzymes, proline oxidase and pyrroline 5-carboxylate (P5C) dehydrogenase. In this paper we report an 800-fold purification P5C dehydrogenase from rat liver mitochondria to yield an essentially homogenous protein. The protein, whose Mr is 59,000, is an alpha 2 dimer (Mr = 115,000) in solution with an isoionic point at pH 5.7. The substrates P5C and NAD+ have apparent dissociation constants of 0.16 and 1.0 mM, respectively. Studies have been conducted to see if the conversion of glutamate and NADH to P5C and NAD+ is catalyzed by this enzyme. These studies have established that if the reverse reaction occurs the rate is 1/15,000th of the rate at which P5C is oxidized to glutamate. The concentration of the substrates needed in the assay results in a high background that interferes with accurate spectrophotometric analysis of the rate of NADH production; therefore a radiochemical (2) or a new colorimetric (3) assay was used here. A number of aldehydes were tested as substrates. It was found that the rat and human enzymes (4) have similar requirements for an aldehyde to be a substrate. Both of these proteins interacted with a polyclonal rabbit anti-rat P5C dehydrogenase serum. PMID- 2211728 TI - The folate cofactor of Escherichia coli DNA photolyase acts catalytically. AB - Escherichia coli DNA photolyase catalyzes the light-driven (300-500 nm) repair of pyrimidine dimers formed between adjacent pyrimidine bases in DNA exposed to UV light (200-300 nm). The light-driven repair process is facilitated by two enzyme bound cofactors, FADH2 and 5,10-methenyltetrahydrofolate. The function of the folate has been characterized in greater detail in this series of experiments. Investigations of the relative binding affinities of photolyase for the monoglutamate and polyglutamate forms of 5,10-methenyltetrahydrofolate show that the enzyme has a greater affinity for the naturally occurring polyglutamate forms of the folate and that the exogenously added monoglutamate derivative is less tightly associated with the protein. Multiple turnover experiments reveal that the folate remains bound to photolyase even after 10 turnovers of the enzyme. Examination of the rates of repair by photolyase containing stoichiometric folate in the presence or absence of free folate under multiple turnover conditions and at micromolar concentrations of enzyme also demonstrates that the folate acts catalytically. The stimulation of turnover by exogenous folate seen at low concentrations of photolyase is shown to be due to the lower affinity of photolyase for the monoglutamate derivative used in reconstitution procedures. These results demonstrate that the folate of E. coli DNA photolyase is a bona fide cofactor and does not decompose or dissociate during multiple turnovers of the enzyme. PMID- 2211730 TI - Substructural analysis of the insulin receptor by microsequence analyses of limited tryptic fragments isolated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the absence or presence of dithiothreitol. AB - Human placental insulin receptor contains 47 Cys per an alpha beta dimer. Most of the 94 Cys in an intact alpha 2 beta 2 receptor are expected to form interchain or intrachain disulfide bonds, since there appears to be only one free cysteine residue in each beta subunit. In order to gain more insight into the three dimensional organization of the insulin receptor, we have used limited trypsin digestion, SDS-PAGE, and protein microsequencing. The present study revealed the following; major tryptic cleavages occurred at alpha 164, alpha 270, alpha 582, and beta 1115, generating Mr 175,000, 130,000, 100,000, 70,000, and 55,000 disulfide-linked complexes. Under reducing conditions, tryptic fragments of Mr values = 30,000, 70,000, 20,000, 55,000, and 20,000 were identified to be alpha(1 164), alpha(165-582), alpha(165-270), alpha(271-582), and alpha(583-C-terminal), respectively. The major beta subunit tryptic fragment of Mr = 55,000 was assumed to have beta(724-1115) or beta(N-terminal-392). The Mr 175,000 complex appeared to contain two alpha(1-164) and two alpha(165-582), whereas the Mr 70,000 complex contained alpha(583-C-terminal) and beta(724-1115). Tryptic cleavage at alpha 582 apparently produced one Mr 175,000 and two Mr 70,000 complexes, suggesting that the alpha(583-C-terminal) domain interacts with the extracellular domain of the beta subunit by disulfide bonds. Tryptic cleavage at alpha 270 resulting in a formation of one Mr 100,000 complex consisting of two alpha(1-270) and two Mr 130,000 complexes consisting of alpha(271-C-terminal) and beta(724-1115) suggests that Cys residues involved with disulfide bonds between the two alpha subunits are located in the alpha(1-270) domain. The identification of the Mr 55,000 complex consisting of small tryptic fragments between alpha(122-270) indicates that 40 Cys residues in the two alpha(122-270) domains are inter- and intramolecularly associated by disulfide bonds. The alpha(1-121) domain does not appear to be linked to any other domains by disulfide bonds. These results are consistent with the structural model that the N-terminal domains of alpha subunits (122-270) are disulfide-linked together while the C-terminal domain (583 C-terminal) of the alpha subunit is linked to the N-terminal domain of the beta subunit by disulfide bonds. PMID- 2211731 TI - Physiological properties and differential glycosylation of phosphorylated and nonphosphorylated forms of osteopontin secreted by normal rat kidney cells. AB - In a previous study we have shown that normal rat kidney (NRK) cells in vitro secrete a 69-kDa osteopontin in both phosphorylated (pp69) and nonphosphorylated (np69) forms. Only pp69 interacts with the cell surface and np69 forms a heat dissociable complex with plasma fibronectin, suggesting functional modulation of osteopontin by phosphorylation. Using tunicamycin, an inhibitor of N-linked glycosylation, and peptide:N-glycosidase F, which removes N-linked oligosaccharide chains from glycoproteins, we show here that np69, but not pp69, contains N-linked carbohydrates. Our results also demonstrate that tunicamycin treatment does not inhibit the cell surface binding of pp69; however, np69 secreted by the treated cells fails to complex with plasma fibronectin, suggesting importantly, our data show that pp69 forms a heat-stable complex with cell surface fibronectin, suggesting that it is an integral component of the extracellular matrix of NRK cells. Finally, sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of deglycosylated and in vitro translated osteopontin suggests that the acidic nature of osteopontin as well as its post translational modifications play a role in the anomalous behavior of osteopontin in sodium dodecyl sulfate gels, observed in several laboratories. The data presented here provide evidence for possible functional roles of 69-kDa osteopontin and suggest that its physiological properties are regulated by post translational modifications. PMID- 2211732 TI - Power equations in endurance sports. AB - This paper attempts to clarify the formulation of power equations applicable to a variety of endurance activities. An accurate accounting of the relationship between the metabolic power input and the mechanical power output is still elusive, due to such issues as storage and recovery of strain energy and the differing energy costs of concentric and eccentric muscle actions. Nevertheless, an instantaneous approach is presented which is based upon the application of conventional Newtonian mechanics to a rigid segment model of the body, and does not contain assumptions regarding the exact nature of segmental interactions- such as energy transfer, etc. The application of the equation to running, cycling, speed skating, swimming and rowing is discussed and definitions of power, efficiency, and economy are presented. PMID- 2211733 TI - A theoretical and numerical approach to optimal positioning of the patellar surface replacement in a total knee endoprosthesis. AB - The clinical results of total knee joint arthroplasty with patellar replacement have shown that postoperative problems arise, especially under unfavourable biomechanical conditions. The findings concerning retropatellar contact forces have been obtained by means of different methods, partly through experimental investigations and partly through theoretical considerations. But so far patellar replacement criteria and the resulting changes of the retropatellar contact force were not taken into consideration in other studies. Our mathematical model is based on a mechanical one and the parameter study considers the influence of the height of the patellar surface replacement upon different biomechanical parameters at varying positions. The results suggest that the patellar replacement should therefore be kept as low as possible, thus reducing the retropatellar contact force to a minimum, especially in the extremely stressed flexion areas of up to about 90 degrees. PMID- 2211734 TI - Toward an identification of mechanical parameters initiating periosteal remodeling: a combined experimental and analytic approach. AB - The ability of bone to adapt to its mechanical environment is well recognized, although the specific mechanical parameters initiating or maintaining the adaptive responses have yet to be identified. Recently introduced mathematical models offer the potential to aid in the identification of such parameters, although these models have not been well validated experimentally or clinically. We formulated a complementary experimental/analytic approach, using an animal model with a well-controlled mechanical environment combined with finite element modeling (FEM). We selected the functionally isolated turkey ulna, since the loading could be completely characterized and the periosteal adaptive responses subsequently monitored and quantified after four and eight weeks of loading. Known loads input into a three-dimensional, linearly elastic FEM of the ulna then permitted full-field mechanical characterization of the ulna. The FEM was validated against a normal strain-gaged turkey ulna, loaded in vivo in an identical fashion to the experimental ulnae. Twenty-four candidate mechanical parameters were then compared to the quantified adaptive responses, using statistical techniques. The data supported strain energy density, longitudinal shear stress, and tensile principal stress/strain as the mechanical parameters most likely related to the initiation of the remodeling response. Model predictions can now suggest new experiments, against which the predictions can be supported or falsified. PMID- 2211735 TI - Relationship between moments at the L5/S1 level, hip and knee joint when lifting. AB - A study was performed to determine the influence of load magnitude on the self selected technique of lifting. Specifically, it was hypothesized that with heavier weights a tendency would occur to lift more with the back and less with the legs. Flexion-extension moments at the L5/S1 level, hip and knee joints were calculated for subjects when lifting boxes weighing from 50 to 250 N. Lifts were performed using a freestyle technique at normal speed. The moment profiles (moment plotted vs time) were analyzed kinematically and as a function of the weight lifted. The kinematics of the lift changed as the weight increased. The moment at the L5/S1 level increased with increasing weight, however, the corresponding knee moment decreased. Thus, an inverse relationship was found between the moment at the L5/S1 level and the knee joint moment. An increase in weight lifted was also associated with an increase in the angular velocity at the knee while lifting. Apparently with heavier weights there is a tendency to extend the knees earlier during the lift than with lighter weights, confirming our hypothesis. This explains the reduced knee moment. Our findings lead to the hypothesis that quadriceps muscle strength limits the subjects' ability to lift with their knees flexed. PMID- 2211736 TI - Effects of surface roughness on the coefficients of friction in model orthodontic systems. AB - Orthodontists, like others (Engel, P.A. (1976) Impact Wear of Materials. Elsevier Scientific, New York.), often equate the smoothness of surfaces with the absence of friction. To investigate whether the surface roughness of opposing materials influence the coefficients of friction and ultimately the movement of teeth, arch wires were slid between contact flats to simulate orthodontic arch wire-bracket appliances. From laser specular reflectance measurements, the RMS surface roughness of these arch wires varied from 0.04 microns for stainless steel to 0.23 microns for nickel titanium. Using the same technique, the roughnesses of the contact flats varied from 0.03 microns for the 1 micron lapped stainless steel, to 0.26 microns for the as-received alumina. After each of the arch wire contact flat couples was placed in a friction tester, fifteen normal forces were systemically applied at 34 degrees C. From plots of the static and kinetic frictional forces vs the normal forces, dry coefficients of friction was obtained that were greater than those reported in the dental literature. The all-stainless steel couples had lower kinetic coefficients (0.120-0.148) than the stainless steel-polycrystalline alumina couple (0.187). When pressed against the various flats, the beta-titanium arch wire (RMS = 0.14 microns) had the highest coefficients of friction (0.445-0.658), although the nickel titanium arch wire was the roughest (RMS = 0.23 microns). Scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDX) verified that mass transfer of the beta titanium arch wire occurred by adhesion onto the stainless steel flats or by abrasion from the sharply faceted polycrystalline alumina flats. PMID- 2211737 TI - A technique for normalizing centre of pressure paths. AB - Centre of pressure paths may be expected to provide useful information in the analysis of gait. In this paper, a technique for normalizing and averaging centre of pressure paths is presented. It utilizes force data obtained from force platform measurements together with information about the placement of the foot on the force platform. This placement is described by specifying the location of the 'centre' and 'midline' of the foot which are defined for a footprint. The coordinate system associated with a footprint is defined and centre of pressure locations are determined in relation to this system. A comparison of the centre of pressure paths obtained using this method and the method proposed by Cavanagh [J. Biomechanics 11, 487-491 (1978)] shows significant differences. It is concluded that the selection of an appropriate technique to obtain centre of pressure paths is important. PMID- 2211738 TI - Three-dimensional measurement of rearfoot motion during running. AB - Excessive ranges of motion during running have been speculated to be connected to injuries to the lower extremities. Movement of the foot and lower leg has commonly been studied with two-dimensional techniques. However, differences in the alignment of the longitudinal axis of the foot with the camera axis will produce measurement errors for projected angles of the lower extremities. A three dimensional approach would not have this limitation. The purpose of this study is to present a three-dimensional model for calculation of angles between lower leg and foot, lower leg and ground, and foot and ground, and to compare results from treadmill running derived from this model with results derived from a two dimensional model for different alignment angles between foot axis and camera axis. A two camera Selspot system was used to obtain three-dimensional information on motion of the studied segments. It was found that several two dimensional variables measured from a posterior view are very sensitive to the alignment angle between the foot and the camera axis. Some variables change as much as 1 degrees for every 2 degrees of change of the alignment angle. The large influence of rotations other than the measured one in two-dimensional measurements makes advisable the use of a three-dimensional model when studying motion between foot and lower leg during running. PMID- 2211739 TI - Use of a transmission ultrasonic technique for the in vitro evaluation of bone ingrowth. PMID- 2211740 TI - Density of trunk tissues of young and medium age people. AB - In this study the investigations made on about 50 trunk tissue densities are described. They were performed on ten cadavers of both sexes within 24 h of the moment of death. They were 20-40 yr old. The weight of each tissue was measured on a laboratory scale and the volume by placing the tissue in a pycnometer filled with water. The density of 2/3 solid trunk tissues ranged from 1.11 to 1.20 g cm 3. The lowest mean data was obtained for a lung tissue (0.563 g cm-3). The highest density datum known from the literature was that for a compact bone: 1.892 g cm-3. The application of obtained data can be for building dummies (e.g. in experiments of car-crash simulations), as well as in the calculation of inertia values using computerized tomography images. PMID- 2211741 TI - Adjustments to the segment center of mass proportions of Clauser et al. (1969). AB - One of the most commonly-referenced studies on body segment masses and centers of mass is by Clauser et al. (AMRL Technical Report 69-70, Wright Patterson Air Force Base, 1969). The Clauser et al. data, however, are difficult to use, because the investigators used certain bony landmarks rather than joint centers as reference points for the center of mass proportions. The purpose of this study was to make adjustments to those proportions so that they could be applied directly to segments having joint centers as endpoints. The segments affected by these adjustments were the trunk, upper arm, forearm, thigh, and calf. These new proportions are markedly different than those originally reported by Clauser et al., especially for the trunk segment. Readers are cautioned against using the original proportions when using joint centers as segment endpoints. PMID- 2211742 TI - A new canine model to evaluate the biological response of intramedullary bone to implant materials and surfaces. AB - A new canine model utilizing an implantable chamber with multiple bone ingrowth channels has been used to study the response of intramedullary bone to various implant materials and surfaces. The first group of dogs received implants containing channels lined by smooth-surfaced coupons of titanium, titanium alloy, sputter-hydroxyapatite-coated (HA-coated) titanium alloy, and polyethylene. A pattern of early initial bone ingrowth by 2 weeks, becoming maximal at 6 to 12 weeks with remodeling to a more mature lamellar bone, and later resorption by 24 weeks was seen for all test groups, with fibrous tissue interfaces covering the smooth test coupons at all time points. Significantly increased bone ingrowth in the sputter-HA coated group was found only at 6 weeks. The second group of dogs received implants with channels lined by surface-roughened coupons of either titanium or plasma-HA-coated titanium, half of which were also packed with a crystalline-HA grouting at the time of surgery. At both 6 and 12 weeks, bone ingrowth was greatly enhanced by the presence of the plasma-HA coating or the crystalline-HA grouting as compared to the uncoated titanium channels. Histologically, bone was seen to bond directly to the plasma-HA coating and the crystalline-HA grouting. A thin fibrous tissue layer was noted between bone and the titanium in most areas, but evidence of direct bone contact to the metal surface was seen. Mechanical testing in tension of intact coupon-bone-coupon units revealed significant strength of the bone-plasma-HA bond, with failure initiating at the metal-HA interface with forces of 15.3 N at 6 weeks, increasing to 44.8 N at 12 weeks. Plasma-HA-lined channels with crystalline-HA packing required similar forces for failure. No significant adhesion strength was noted for the titanium channels at 6 weeks, and only the crystalline-HA-filled channels displayed measurable strength of the bone-titanium interface at 12 weeks, with a force of 9 N needed for failure. PMID- 2211743 TI - Blood compatibility of PEO grafted polyurethane and HEMA/styrene block copolymer surfaces. AB - HEMA/styrene (HEMA/STY) block copolymers and poly(ethylene oxide) 4,000 M.W. (PEO4K) grafted Biomer (B-PEO4K) surfaces have been synthesized, characterized, and evaluated as blood-contacting materials. These surfaces have demonstrated improved blood compatibility, compared to Biomer, in in vitro and ex vivo experiments. Biomer vascular grafts (6 mm I.D. 7 cm in length) were fabricated by a dip coating process. The luminal surface was modified either with PEO grafting, HEMA/STY coating, or Biomer coating (control). These surface-modified grafts were implanted in the abdominal aortas of dogs and evaluated for graft patency and protein adsorption. Surface protein layer thickness was measured by transmission electron microscopy (TEM). B-PEO4K and Biomer showed thick multilayers of adsorbed proteins (1000-2000 A) after 3 weeks to 1 month implantation. In contrast, HEMA/STY only showed a monolayer protein thickness (less than 200 A), even after 3 months. Visualization of adsorbed plasma proteins (albumin, IgG, and fibrinogen) was performed with scanning electron microscopy (SEM)/TEM using an immunogold double antibody technique. The pattern of protein distribution showed high concentrations of fibrinogen and IgG, and less albumin adsorbed onto Biomer and B-PEO4K. In contrast, HEMA/STY showed a patchy protein distribution pattern with high concentrations of albumin and IgG, and relatively less fibrinogen. Adsorbed monolayer patterns showed improved compatibility over multilayered proteins. The Biomer and B-PEO4K grafts occluded within 1 month, while HEMA/STY grafts were patent for over 3 months. The thin and stable adsorbed protein layer on HEMA/STY surfaces may be associated with the microdomain structures of the surface, and will play an important role in long-term in vivo blood compatibility. This manuscript will evaluate the long-term in vivo performance of these polymers, analyze the extent of protein adsorption onto the surfaces, and correlate protein layer thickness to the thrombogenicity of the polymer surfaces. PMID- 2211744 TI - Sequential polydepsipeptides as biodegradable carriers for drug delivery systems. AB - Sequential polydepsipeptides containing both peptide and ester bonds, poly[(L alanyl)n-gamma-ethyl L-glutamyl-L-lactyl] (n = 0, 1, 2, and 3) (poly[(Ala)n Glu(OEt)-Lac]), were prepared for application as biodegradable carriers for drug delivery systems. The in vivo degradation of these polymers was evaluated by subcutaneous implantation in the backs of male rats, and was strongly influenced by the number (n) of Ala units in poly[(Ala)n-Glu(OEt)-Lac]. The resulting poly(Ala-Ala-Glu(OEt)-Lac) gave the highest degradability, in which 100% degradation was observed 24 weeks from the start of implantation. A luteinizing hormone-releasing hormone agonist des-Gly10-[D-Leu6]-LH-RH ethylamide (LH-RH agonist), was incorporated into a sequential poly(Ala-Ala-Glu(OEt)-Lac) carrier by the melt-pressing technique, which gave fine cylindrical polymer formulations with different structures of drug dispersion, e.g., blend-type and sandwich-type formulations. The rate of in vivo release of LH-RH agonist from a blend-type formulation showed a linear decrease with time until its release was finished after 6 weeks' implantation. In contrast, in a sandwich-type formulation, the in vivo release rate was apparently maintained constant over a period of 16 weeks (24 +/- 14 micrograms/day). PMID- 2211745 TI - Titanium-coated micromachined grooves of different dimensions affect epithelial and connective-tissue cells differently in vivo. AB - A desirable feature of an implant surface which penetrates epithelium would be that the surface impedes epithelial downgrowth. Previous experiments have shown that the micromachined, horizontally oriented grooves on the percutaneous implant surface can impede epithelial downgrowth (Chehroudi et al., J. Biomed. Mater. Res., 22, 459 (1988) and 23, 1067 (1989)). However, little is known of the effect of varying groove parameters such as depth, spacing, and orientation on epithelial downgrowth and attachment of epithelial (E)-cells and fibroblasts (F) to percutaneous implants in vivo. Grooves were produced with a 30-micron pitch and depths of 22 microns, 10 microns, or 3 microns. In addition, 10-microns- and 3-microns-deep grooves were made with pitches of 39 microns and 7 microns, respectively. Implants with grooves oriented either horizontally or vertically to the long axis of the implant as well as smooth control surfaces were coated with 50 nm of titanium and placed in the parietal area of rats for a period of 7 days. Close attachment of E-cells was found on the smooth, 10-microns- and 3-microns deep, horizontally or vertically aligned grooved surfaces; in contrast, E-cells bridged over the 22-microns-deep, horizontally oriented grooves. F formed a capsule on the smooth surface as well as the 10-microns- and 3-microns-deep horizontally oriented grooves, but F inserted obliquely into the 22-microns-deep, horizontally aligned grooved surface. Histomorphometric measurements indicated that the epithelial downgrowth was greatest on the vertically oriented grooved and smooth surfaces and was shortest on the 22-microns-deep and 10-microns-deep horizontally aligned grooved surfaces. These differences indicate that epithelial downgrowth was accelerated on the vertically oriented grooved surfaces and inhibited on the horizontally oriented grooved surfaces. Moreover, the mechanism of inhibition of the epithelial downgrowth may differ among these surfaces. E cells bridged over the 22-microns-deep grooves and their migration appeared to be inhibited by the F that inserted into the implant surface. In the shallower horizontal grooves, however, epithelial downgrowth was probably inhibited by contact guidance because there was no evidence of F inserting obliquely into the implant surface. PMID- 2211746 TI - Macromolecular release from collagen monolithic devices. AB - Collagen monolithic devices varying in crosslinking density, collagen structure, and crosslinker were fabricated. In vitro release rates of a model macromolecule, inulin, were found to be linear with t1/2 and were affected by crosslinking density, nature of crosslinker, and collagen structure. The biodegradation of the collagen matrix was also examined. Proteolytic enzymes did not degrade the collagen devices; the degradation rate with collagenase was dependent on collagen structure, crosslinker, crosslinking density, and enzyme concentration. In vivo biocompatibility, degradation, and 14C-inulin release rates were evaluated subcutaneously in rats. After 3 weeks, none of the collagen discs induced any severe cellular response. Dacron induced a stronger fibroblast response but fewer inflammatory cells as compared to the collagen discs. No significant degradation of the collagen discs occurred within 3 weeks. In vivo release of 14C-inulin from collagen monolithic devices was diffusion controlled. PMID- 2211747 TI - Microencapsulation of mammalian cells in a HEMA-MMA copolymer: effects on capsule morphology and permeability. AB - A new process for preparing uniform microcapsules with a hydroxyethyl methacrylate-methyl methacrylate copolymer (HEMA-MMA) has been devised. Capsule diameters were 900-1000 microns in diameter, (+/- 10-20 microns, +/- SD) depending on the precipitation conditions. The process involved the coextrusion of polymer solution (in PEG 200) and the mammalian cell suspension (here erythrocytes) through a needle assembly which is submerged in a layer of hexadecane which is in turn sitting above a stirred isotonic aqueous solution in a volumetric flask. The needle is repeatedly withdrawn from the hexadecane overlayer shearing a droplet from the needle tip which falls into the water, where the solvent is extracted to precipitate the polymer around the cells to yield the capsules. The morphology of the capsule wall was altered by changing the precipitation bath from phosphate buffered saline (PBS) to 0.3 M glycerol. This resulted in greater macroporosity in the wall, presumably because of the faster precipitation due to the higher solvent/precipitant compatibility with 0.3 M glycerol. The permeability to a series of test solutes (glucose, inulin, albumin, and alcohol dehydrogenase, ADH) increased by a factor of approximately 2, presumably because of the increased macroporosity. Addition of 15% water to the polymer solvent enhanced the macroporosity, presumably by bringing the system closer to the cloud point; however, there was no corresponding increase in permeability. There was a significant decrease in permeability between that of albumin (approximately 69,000 D) and ADH (approximately 150,000 D) suggesting that the molecular weight cut-off of these capsules was on the order of 100,000 D as desired. This process is now being evaluated for the encapsulation of pancreatic islets and other cells of potential clinical interest. PMID- 2211748 TI - Diagnosing malignant bone tumours. PMID- 2211749 TI - The effect of improved cementing techniques on component loosening in total hip replacement. An 11-year radiographic review. AB - Improved cementing techniques have been shown to decrease the rate of aseptic loosening of femoral components of cemented total hip replacements at five to seven years. We now report our results in 105 hips in 93 patients at 10 to 12.7 years (mean 11.2). The improved techniques included use of a medullary plug, a cement gun, a doughy mix of Simplex P and a collared stem of chrome cobalt. Only three femoral components had definitely loosened, none were probably loose and 24 were graded as possibly loose. In contrast, the incidence of radiographic loosening on the acetabular side was 42%. Improved cementing techniques have produced a marked reduction in the rate of aseptic loosening of the femoral component, but the incidence of acetabular loosening is unchanged. PMID- 2211750 TI - Total hip arthroplasty after fracture of the acetabulum. Long-term results. AB - We made a retrospective study of 55 primary total hip arthroplasties in 53 patients with a history of previous acetabular fracture. The mean follow-up was 7.5 years and the average age at fracture was 48.7 years. The incidence of radiographic femoral loosening (29.4%), symptomatic loosening (15.7%), and femoral revision (7.8%) were similar to those previously reported at 10 years for routine arthroplasties by Stauffer (1982). On the acetabular side, the incidence of radiographic loosening (52.9%), symptomatic loosening (27.5%), and revision (13.7%) were four to five times higher. We conclude that a history of prior acetabular fracture has a significant adverse impact on the long-term outcome of any subsequent total hip arthroplasty. PMID- 2211751 TI - Chiari pelvic osteotomy for osteoarthritis. The influence of the torn and detached acetabular labrum. AB - We assessed the results of Chiari pelvic osteotomy in 64 hips with early osteoarthritis in terms of acetabular labral detachment detected pre-operatively by arthrography. At an average follow-up of four years, assessment by the Merle d'Aubigne score showed 83% excellent or good results. These satisfactory results were achieved in only half the cases with a detached labrum, but in nearly all cases with normal or torn acetabular labra. Other factors such as the acetabular index, the level and angle of osteotomy, and the displacement following osteotomy did not affect the results. Chiari pelvic osteotomy is a worthwhile procedure for early osteoarthritis in selected cases, but a detached acetabular labrum increases the risk of clinical failure. PMID- 2211752 TI - Blood loss reduced during hip arthroplasty by lumbar plexus block. AB - We measured the blood loss during and after hip replacement in two groups of women, each consisting of 10 patients. In one group the lumbar plexus was infiltrated with bupivacaine, in the other it was not. The group in whom the plexus was blocked had significantly less blood loss. PMID- 2211753 TI - Simultaneous or staged bilateral total knee replacements in rheumatoid arthritis. A prospective study. AB - In a prospective study of 100 knee arthroplasties in patients with rheumatoid arthritis, simultaneous bilateral surgery was compared with staged bilateral replacements. All patients had improved function following their operations but those who had staged surgery only achieved maximum benefit after the second knee had been replaced. The complication rate was no greater for simultaneous surgery and we therefore advocate the method for those patients who require bilateral replacements. PMID- 2211754 TI - The Oxford knee replacement. A review from an independent centre. AB - We present a study of 67 Oxford bicompartmental total knee replacements performed at a district general hospital. In this general orthopaedic unit, 57 of the knees (85%) had significant relief of pain with a mean flexion range of 95 degrees and a mean flexion deformity of only 9 degrees. There was a noticeable difference between osteoarthritic and rheumatoid knees. Poor results could be directly related to an avoidable postoperative complication. The results of this independent assessment may be compared favourably with the previously published series from the specialist centre at which the prosthesis was designed. PMID- 2211756 TI - Secondary total hip replacement after fractures of the femoral neck. AB - We studied the rate of revision in 84 consecutive total hip replacements performed for failed osteosynthesis of femoral neck fractures and compared it with that for primary arthroplasty for osteoarthritis. The age and sex adjusted risk of prosthetic failure was 2.5 times higher after failure of fixation, but all the excess risk was in patients over 70 years of age. There were radiographic signs of loosening of the femoral component at five to 12 years after secondary arthroplasty in six of 33 survivors. In general, the results of secondary replacement were no worse than those obtained after primary arthroplasty for femoral neck fracture. We consider that internal fixation should be the primary procedure: total hip replacement is a safe secondary procedure when osteosynthesis fails. PMID- 2211755 TI - The incidence of deep vein thrombosis after cementless and cemented knee replacement. AB - The incidence of deep vein thrombosis in 244 patients who had total knee replacement has been studied. In 120 the prosthesis was cemented and in 124 it was cementless. In all cases the replacement was primary and a porous-coated prosthesis with a porous-coated central tibial stem was used. Deep vein thrombosis was diagnosed by venography, and pulmonary embolism by perfusion scanning. The incidence of deep vein thrombosis in the cementless knees (23.8%) and in the cemented (25%) was approximately the same. The only significant predisposing factors for deep vein thrombosis in both groups were obesity, prolonged postoperative immobilisation, previous venous disease and hyperlipidaemia. PMID- 2211757 TI - The Hastings bipolar hemiarthroplasty for subcapital fractures of the femoral neck. A 10-year prospective study. AB - In a 10-year prospective study, 561 displaced subcapital fractures of the femoral neck in 546 patients were treated with the Hastings bipolar hemiarthroplasty. Within six months of their operations, 148 patients had died. In 322 hips followed up, 243 with adequate serial radiographs separated by more than one year, only 14 (5.6%) showed acetabular erosion. A group of 91 had been reviewed for between three and nine years (mean, 4 years 10 months) and of these, 95% had no pain or slight pain only. Comparison with an earlier series of conventional hemiarthroplasties reported from this institution showed that the clinical results were similar, but that the erosion rate had been halved. PMID- 2211758 TI - The AO dynamic hip screw and the Pugh sliding nail in femoral head fixation. AB - We compared, under laboratory conditions, the resistance to cutting out of the AO dynamic hip screw and the Pugh sliding nail. The mean load at cut out, adjusted for bone strength, was 70% greater for the Pugh sliding nail. The reasons for this difference are discussed. PMID- 2211759 TI - Femoral neck fracture fixation. Comparison of a sliding screw with lag screws. AB - The rigidity of a sliding compression screw and three cannulated lag screws in the treatment of subcapital fractures was compared in five pairs of female cadaver femora. There were no significant differences between the compressive strength, bone density, cortical thickness or Singh index of the bones in each pair. A subcapital fracture was standardised using a perpendicular saw cut across the femoral neck. A uniaxial 'load test system' with force and length measurement facilities was used to mimic cyclical stressing applied in vivo at a frequency of 0.5 Hz from 0 to 3 times body-weight. There was no significant difference between the fixation afforded by the sliding compression screw and three lag screws. Bone quality was the single most important factor in the stability of the bone implant unit. PMID- 2211760 TI - External fixation for type III open tibial fractures. AB - An analysis of 51 type III open tibial fractures treated by external skeletal fixation is presented. The fractures are subdivided according to the classification of Gustilo, Mendoza and Williams (1984) into types IIIa, IIIb and IIIc. The different prognoses of these fracture subtypes is examined. The use of the Hoffmann and Hughes external fixators in the management of type III open tibial fractures is presented and it is suggested that the prognosis is independent of the type of fixator used. PMID- 2211761 TI - Locked intramedullary nailing for displaced tibial shaft fractures. AB - We analysed the results of 93 tibial shaft fractures treated with the Grosse Kempf locked nail. Twenty-six fractures were comminuted, 19 were open grade I to II, and 54 were located outside the middle third of the tibia. The deep infection rate was 3.2%. There were only two poor results. The use of this method is recommended and discussed. PMID- 2211762 TI - Reduction of post-traumatic swelling and compartment pressure by impulse compression of the foot. AB - Following the discovery of a powerful venous pump in the foot that is activated by weight-bearing independently of muscular action, a pneumatic impulse device was developed to actuate this pump artificially. In a multicentre international trial the device was shown to reduce post-traumatic and postoperative swelling; pain also was alleviated. Evidence is also presented that dangerously high compartment pressures may be reduced to acceptable levels and fasciotomy avoided. We present an explanation of the clinical effects of activation of the venous footpump, based on recent improved understanding of the physiology of the microcirculation. The hyperaemic response that follows the liberation of endothelial-derived relaxing factor (EDRF) by sudden changes of pressure after weight-bearing or impulse compression is particularly important. PMID- 2211763 TI - Mechanism of the pivot shift. AB - The mechanism of the pivot shift was investigated by analysing movements under valgus torque in 29 fresh cadaveric knees. The movements were measured in three dimensions, using biplanar photography, when all the ligaments were intact, and then after the ligaments were sequentially divided. When only the anterior cruciate ligament was sectioned, the pivot shift occurred in seven out of 20 knees examined. In the other 13, though the pivot shift was not observed, an abnormal internal rotation occurred at between 10 degrees and 50 degrees of flexion. Division of the iliotibial tract in addition to division of the anterior cruciate ligament stopped the pivot shift, as the tibia remained internally rotated throughout the range of flexion. The axis of rotation of the pivot shift was located at the medial collateral ligament, which was kept tight by the applied valgus torque. The sudden movement in the pivot shift was caused by a complex interaction between the geometry of the knee and the valgus torque applied. PMID- 2211764 TI - The osteogenetic potential of fracture haematoma. Subperiosteal and intramuscular transplantation of the haematoma. AB - We studied the precise role of the fracture haematoma in healing by the experimental transplantation of the haematoma at two days and four days after fracture of the rat femur to subperiosteal and intramuscular sites. We used bone marrow and peripheral blood haematomas for control experiments. The transplanted two-day fracture haematoma produced new bone by endochondral ossification at the subperiosteal site, but not at the intramuscular site. Four-day fracture haematoma produced new bone formation at both subperiosteal and intramuscular sites. These results suggest that fracture haematoma has an inherent osteogenetic potential. PMID- 2211765 TI - Healing of non-vascularised diaphyseal bone transplants. An experimental study. AB - Four different experiments were performed to study the healing of a large, non vascularised, diaphyseal, bone segment in adult cats. In the first experiment, a 4 cm segment of tibia with its periosteum was excised and replaced in its bed. The other experiments were similar, except that in the second, the periosteum of the segment was removed, in the third its medullary canal was blocked with a Silastic rod, and in the last group the segment was isolated from its muscle bed by a Silastic sheet. The reparative processes were quantified by estimating the resorption index, the cortical new bone formation index, the callus encasement index, and the osteocyte count. Bone resorption and apposition occurred in the segment even when the periosteum was absent or the medullary canal was blocked, with osseous union at both ends by eight to 12 weeks, provided the segment was not isolated from its muscle bed. Thus, the muscle bed played a significant role in these reparative processes. PMID- 2211766 TI - Corticocancellous grafting and an AO/ASIF lag screw for nonunion of the scaphoid. A retrospective analysis. AB - We report our experience in 42 patients, using corticocancellous bone grafts and lag screw fixation for un-united scaphoid fractures. Using a grading system, we analysed the suitability of the method for three types of nonunion. We recommend the operation for the treatment of scaphoid nonunion, except where there is avascular necrosis of the proximal pole. PMID- 2211767 TI - The management of the painful first metatarsophalangeal joint in the older patient. Arthrodesis or Keller's arthroplasty? AB - We report a prospective randomised trial comparing Keller's arthroplasty and arthrodesis of the first metatarsophalangeal joint for the management of symptomatic hallux valgus and hallux rigidus in the older patient. In 81 patients (110 feet), with a minimum of two years follow-up, both procedures gave a similar degree of patient satisfaction and symptom relief. The incidence of metatarsalgia was also similar. As there were no obvious advantages to arthrodesis, and since six out of 50 arthrodesed toes required revision, we suggest that Keller's arthroplasty is the better operation in these patients. PMID- 2211768 TI - Glenohumeral elevation studied in three dimensions. AB - We studied the position and rotational changes associated with elevation of the glenohumeral joint, using a three-dimensional magnetic-field tracking system on nine fresh cadaveric shoulders. The plane of maximal arm elevation was shown to occur 23 degrees anterior to the plane of the scapula. Elevation in any plane anterior to the scapula required external humeral rotation, and maximal elevation was associated with approximately 35 degrees of external humeral rotation. Conversely, internal rotation was necessary for increased elevation posterior to the plane of the scapula. The observed effects of this rotation were to clear the humeral tuberosity from abutting beneath the acromion and to relax the inferior capsular ligamentous constraints. Measurement of the obligatory humeral rotation required for maximal elevation helps to explain the relationship of the limited elevation seen in adhesive capsulitis and after operations which limit external rotation. PMID- 2211769 TI - Neonatal osteomyelitis. AB - Thirty-four neonates with osteomyelitis were reviewed. The hip (19) was the most common site involved. Swelling and pseudoparalysis were the most significant local signs. Radiographic abnormalities, such as metaphyseal rarefaction and/or joint subluxation were found on the initial radiographs in 18 of the 19 hips involved. All patients were treated with antibiotics and all infections involving joints were drained surgically. Good results were achieved in 75% of all sites and in 68% of hips. PMID- 2211770 TI - Ultrasound-guided aspiration for transient synovitis of the hip. AB - We reviewed 15 children with transient synovitis of the hip who had aspiration of an effusion under local anaesthesia with ultrasound guidance. There were no significant complications; aspiration was useful for diagnosis and gave considerable symptomatic relief. We discuss the role of ultrasound in diagnosis and treatment. PMID- 2211771 TI - Surgical treatment for severe slipping of the upper femoral epiphysis. AB - We have used a modified technique of cervical osteotomy to treat a consecutive series of 23 patients with chronic slip of the upper femoral epiphysis. It has been successful in correcting both moderate and severe deformities with a low incidence of avascular necrosis, comparable to that seen after subtrochanteric osteotomies. We describe the operative details and discuss the features which make cervical osteotomy technically superior to intertrochanteric and subtrochanteric procedures. PMID- 2211772 TI - The lateral condylar prominence. A complication of supracondylar osteotomy for cubitus varus. AB - We reviewed 27 patients who had supracondylar closing wedge osteotomy for cubitus varus. There were 10 excellent and 12 good results. However, of these 22 patients, 14 had a significant bony prominence over the lateral condylar region caused by lateral displacement of the elbow when closing the osteotomy. This prominence was less obvious in patients who had their osteotomy at a young age, but worse after operations near or after skeletal maturity. This difference appeared to be due to remodelling. PMID- 2211773 TI - Transient cyst-like cortical defects following fractures in children. Medullary fat within the subperiosteal haematoma. AB - Asymptomatic cyst-like cortical defects appearing after fractures in children have been occasionally reported. Typically, these defects appear during fracture consolidation, within the newly formed subperiosteal bone, proximal to the fracture line, do not enlarge, and progressively disappear. We have previously shown a fatty density on CT scan within the early cortical defect. We now present two additional cases in which early CT scans appeared to confirm that these transient cortical defects may consist of fat, and probably result from the inclusion of medullary fat within the subperiosteal haematoma. PMID- 2211774 TI - The structure of the human subchondral plate. AB - To study the anatomy of subarticular bone and cartilage, fresh specimens of cartilage on bone from the human shoulder, hip and knee were treated with bleach or papain, or were fixed and decalcified. All were compared using scanning electron microscopy. Papain digestion selectively removed cartilage to the tidemark. The tidemark contour was highly variable; irregularities were indirectly related to degenerative lesions and were most prominent in peripheral non-weight-bearing areas of joints with central fibrillation. Decalcification exposed the interface between the bone and calcified cartilage. Collagen fibrils in articular cartilage did not interdigitate with those of bone. The subchondral bone was appositional, avascular, smooth and very thin in most areas of human joints. Perforations through subchondral bone or calcified cartilage were rare. Bleach maceration destroyed important details. PMID- 2211775 TI - Extensor indicis proprius transfer for rupture of the extensor pollicis longus tendon. AB - We reviewed 21 patients with 22 ruptures of the extensor pollicis longus at a mean of 5.3 years after transfer of the extensor indicis proprius tendon. Of these, 19 with 21 transfers described the result as good, and two as fair. The mean deficit of extension between the operated and unoperated thumbs was 1.4 cm, and the mean flexion deficit 0.6 cm. Pressure gauge measurements showed that the strength of the transfer was 51% of that of the uninjured extensor. The two fair results had an extensor lag of over 1.5 cm. Independent extension of the index was maintained in all patients, none having a discernible lag, but the strength of index extension was reduced to 49% of that of the normal finger. There was no evidence of functional loss. Extensor indicis proprius transfer for rupture of the extensor pollicis longus tendon is a simple and reliable procedure with few complications. It gives satisfactory long-term extension of the thumb. PMID- 2211776 TI - Open transpedicular biopsy of the vertebral body. AB - We describe a method of obtaining a biopsy from the body of a vertebra by an open transpedicular route. This minimises the danger of contamination of tissue planes and spaces. PMID- 2211777 TI - A target device for placement of implants in the thoracolumbar pedicles. AB - Posterior spinal instrumentation with the placement of intrapedicular implants has become an important technique. We have designed a hand-held target device to facilitate the open or percutaneous location and penetration of the thoracolumbar pedicles. A cylindrical pin guide incorporates two metal rings and can be moved under image intensifier control until the rings are superimposed to show correct alignment. The radiation dosage for the surgeon is minimal; the device allowed accurate placement of 106 consecutive pedicle screws. PMID- 2211778 TI - Replacement of the lumbar vertebrae of sheep with ceramic prostheses. AB - We prepared a prosthesis for the replacement of the lumbar vertebrae of sheep, using apatite- and wollastonite-containing glass-ceramic. The material is stronger than human cortical bone and has the special feature of chemical bonding to bone. Ten sheep underwent replacement of L3 and L4 vertebrae, without bone grafting. The animals were killed at intervals from three months to 27 months after operation, and the interface between the prosthesis and bone was examined radiologically, histologically and crystallographically. Bone bonding with the prosthesis had occurred in half the implants. It took at least one year for bonding to be complete, but an apatite layer on the surface of the prosthesis was observed as early as three months after the operation, suggesting the possibility of much earlier bone bonding if more rigid fixation of the prosthesis had been provided. PMID- 2211779 TI - The modified Schollner costoplasty. AB - The modified Schollner costoplasty is a cosmetic procedure for the correction of rib prominence deformity in scoliosis. We present the results of the procedure in 21 patients who had previously undergone spinal fusion for scoliosis. We found the procedure to be well tolerated without major complications. Objective cosmetic improvement was achieved in all but one case. All but one patient considered the procedure to have been of cosmetic benefit. PMID- 2211780 TI - Long-term prognosis of soft-tissue injuries of the neck. AB - We reviewed 43 patients who had sustained soft-tissue injuries of the neck after a mean 10.8 years. Of these, only 12% had recovered completely. Residual symptoms were intrusive in 28% and severe in 12%. Pain in the neck and lower back was the commonest complaint and older patients had a worse prognosis. After two years, symptoms did not alter with further passage of time. PMID- 2211781 TI - A surgical approach to the cervicothoracic spine. AB - We describe a method for approaching the lower cervical and upper thoracic spine, the brachial plexus and related vessels. The method involves the elevation of the medial corner of the manubrium, the sternoclavicular joint, and the medial half of the clavicle on a pedicle of the sternomastoid muscle. We have used this exposure in 17 cases with few complications and good results. Its successful performance requires high standards of anaesthesia, surgical technique and postoperative care. PMID- 2211782 TI - Operative and conservative treatment of moderate spondylolisthesis in young patients. AB - We made a retrospective study of 149 children and adolescents with moderate spondylolisthesis (slip less than or equal to 30%), 77 treated by fusion and 72 conservatively at an average follow-up of 13.3 years. Both groups were fully comparable with regard to age at diagnosis, sex distribution (46% girls), and mean slip. The patients who were treated operatively had more pain before treatment and showed more initial progression of the slip. They had better clinical results and less pain at latest review, but the total progression of the slip over the whole follow-up showed no statistical differences between the two groups. Patients with a pseudarthrosis after attempted fusion had had a longer period of postoperative pain, but at the latest review had no more pain than those with sound fusion. None of those treated conservatively came to fusion later and the long-term results in 18 patients who had refused the advised operation were no worse than those for other conservatively treated patients. Our results suggest that a moderate grade of spondylolisthesis in adolescents usually has a benign course. It seems that spontaneous segmental stabilisation occurs as a result of degeneration of the disc at the level of the slip. PMID- 2211783 TI - Lumbar intervertebral disc prolapse in teenage twins. A case report and review of the literature. AB - We report the cases of teenage twin girls presenting within months of each other with severe symptoms from lumbosacral disc prolapses, requiring laminectomy in one and chemonucleolysis in the other. CT scans showed similarities in spinal configuration, including the presence of disc bulges at the L4-5 level. This suggests a strong hereditary factor in prolapse of intervertebral discs, but a review of the literature showed little information on that aspect. PMID- 2211784 TI - Cuneiform rotation osteotomy for relapsed hallux valgus. PMID- 2211785 TI - A lead apron for closed femoral nailing. PMID- 2211786 TI - Compartment syndrome caused by false aneurysm. PMID- 2211787 TI - Brain tumour presenting as a dislocated shoulder. PMID- 2211788 TI - Closed intramedullary nailing of the tibia. PMID- 2211789 TI - Spontaneous rupture of the suprapatellar bursa. PMID- 2211790 TI - Simultaneous slipped upper femoral epiphysis in identical twins. PMID- 2211791 TI - Fatal air embolism during arthroscopy. PMID- 2211792 TI - Ligation of the superficial femoral vein in prevention of pulmonary embolism: an old fashion procedure? AB - From 1974 to 1988, interruption of the superficial femoral vein (SFV) was performed to prevent pulmonary embolism (PE) in 73 patients. The mean age of the patients was 62 years. Phlebography showed thrombi in the following localizations: calf veins (67.3%), superficial femoral or popliteal veins (56.6%), common femoral veins (19.5%) and iliac veins (2.7%). A floating thrombus in the popliteal or femoral vein was the main indication for surgery in 97.3% of patients. Pulmonary embolism had occurred in 76.7% and was associated with neoplasm in 13.7%. Ligation of the SFV was performed in 93 limbs and completed iliac or femoral thrombectomy in 32.3%. The procedure was performed under locoregional anesthesia in 82.9% of the cases. Hospital mortality was 1.4% and 3 year survival, considering only PE related deaths was 95.3 +/- 2.7%. Follow-up was complete for all patients and averaged 3.0 years, for a 3 years PE-free rate of 90.8 +/- 3.6%. Persistent symptoms included increased limb tenseness in 12.5% and mild ankle edema in 25%. Bilateral strain-gauge plethysmography (SGP) was obtained in 65 limbs. The time necessary to obtain a 50, 75 and 100% decrease in calf volume (respectively T1/2, T3/4 and TT) was calculated for the operated limb and compared with the untreated limbs used as controls. A prolongation of T1/2 from 2.5 +/- 0.3 sec in controls to 4.3 +/- 0.4 sec in the operated limb (p less than 0.01) was found. Thus, our experience with ligation of the superficial femoral vein is favourable since long-term ill effects have been minimal and strain gauge plethysmography (SGP) showed only mildly altered venous drainage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2211793 TI - The relationship of intraluminal shunting to technical results after carotid endarterectomy. AB - This study evaluates the incidence of defects on the intraoperative angiograms of 160 carotid endarterectomies performed in 146 patients, 81 of 160 (50.6%) with a shunt and 79 of 160 operations (49.4%) performed without a shunt. Angiographic defects were identified in 34 of 160 carotid endarterectomies (21%), of which 21 of 34 (65%) resulted in a greater than 20% stenosis of the internal carotid artery (ICA). There were defects in 6 of 81 (7.4%) shunted vessels compared to 16 of 79 (20%) of those not shunted (p less than 0.05). Thirty-one vessels were reexplored 11 of 81 (13.5%) of those shunted and 20 of 79 (20%) of those not shunted (p less than 0.05). There were four strokes (2.5%) (2 in each group) and one death due to myocardial infarction (0.6%) in the postoperative period. Duplex follow-up from 1-60 months (median 22 months) was available in 114 of 160 (71%) endarterectomies. A stenosis of greater than 50% was detected in 7 of 114 (6%) carotid arteries; 5 of the 7 (71%) were shunted and 2 (29%) were nonshunted. Unrepaired defects were present in 3 of 7 (43%) and no defects in the remaining 4 of 7 (57%) arteries. We conclude that the use of a shunt significantly decreases the number of ICA defects detected angiographically and that immediate revision of demonstrable defects can be undertaken with low morbidity and does not predispose the patient to recurrent stenosis. PMID- 2211794 TI - Long term follow-up of descending thoracic aorto-iliac/femoral bypass. AB - A prospective study of 26 patients undergoing descending thoracic aorto iliac/femoral (DTAI/F) bypass was conducted over a 13-year period with an average follow up of 53 months. Reasons for selecting the procedure were occluded aortic bifurcation grafts (9 patients), hostile abdomen (6), infected aortic graft (1), microaorta (10, and surgeons preference in 8 patients who had juxtarenal aortic occlusion. The operative mortality was 3.8% (1 patient). A late mortality of 36% was due to myocardial infarction (1), lung carcinoma (2), renal failure (4), stroke (1) and pulmonary insufficiency (1). Graft failure occurred in 4 patients at 23, 26, 54 and 109 months respectively. Primary cumulative patency was 86% statistically valid at 42 months. DTAI/F bypass is recommended in selected patients when conventional approaches to the aorta are considered unduly hazardous. PMID- 2211795 TI - Current results of elective aortic reconstruction for aneurysmal and occlusive disease. AB - Decisions to resect small aortic aneurysms or employ non-operative treatment for aorto-iliac occlusive disease must depend on current rather than historical surgical results. To assess current morbidity and mortality, we reviewed 200 consecutive aortic resections in two groups of patients treated from 1981 to 1989: those undergoing elective aortofemoral bypass for occlusive disease (AFB, no. 100) or resection of infrarenal abdominal aortic aneurysms (AAA, no. 100). Indications for AFB included claudication (54%), rest pain (32%), and gangrene (13%). AAA size ranged from 3 to 14 cm (mean 6.5 +/- 2.4 cm); 45% presented with abdominal or back pain. Patients undergoing AFB were younger (AFB 61.5 +/- 10 years vs AAA 68.7 +/- 8.9 years) with a higher incidence of some atherosclerotic risk factors, diabetes mellitus 30% vs 10%, tobacco use 77% vs 49%, hyperlipidemia 21% vs 7%; p less than 0.001). Coronary artery disease (CAD) was more prevalent in AAA patients (49% vs 34%; p less than 0.001). Postoperative mortality was not different in occlusive or aneurysmal disease (3% AFB vs 2% AAA), nor was the occurrence of serious complications such as myocardial infarction (2% vs 1%) or pulmonary embolism (2% vs 3%). Improvements in patient selection, perioperative care and surgical technique have lowered the mortality of elective aortic surgery. Given the current standard of care, an aggressive approach to AAA even in high risk patients is appropriate. The low morbidity of AFB for occlusive disease mandates a critical appraisal of less effective nonoperative therapies. PMID- 2211797 TI - Synchronous reconstruction for combined aortoiliac and femoropopliteal occlusive lesions. The role of proximal bypass. AB - Between January 1984 and December 1986, 31 patients underwent synchronous revascularization (SR) because of the serious clinical condition of a lower limb and presence of arteriographically visible lesions. Average follow-up was 30 months. Operative mortality was 10%. Two patient populations were identified: Group I (N = 13): patients who underwent ilio-femoral or aorto-femoral proximal revascularization (PR); Group II (N = 18): patients who had axillo-femoral PR. Group I patients were younger than those in Group II (64 yr versus 72 yr; p less than 0.01). An association of pre-operative risk factors (arterial hypertension; coronary, renal or respiratory insufficiency) was twice as frequent in Group II as in Group I (p less than 0.02). The rate of SR compared to PR alone was 15%. However, there was no statistically significant difference between Groups I and II. Comparison of the actuarial survival curves for patients ahd the patency rates of SR in Groups I and II failed to reveal any statistically significant differences. Axillo-femoral bypass can be used for PR when SR is necessary in high risk patients. PMID- 2211796 TI - Combined epidural and general anesthesia in aortic surgery. AB - The perioperative course of 144 consecutive patients undergoing aortic reconstructive surgery was studied to assess the potential benefit of employing a combined epidural and light general anesthesia technique. A group of 67 patients had general anesthesia alone (GA), while in the group of 77 remaining patients, a combined epidural and general anesthesia (Epi-GA) was employed. The two groups were similar in regards to age, medical risk factors, preoperative assessment of cardiac and pulmonary function, and type of surgical reconstruction. There was no significant difference in the anesthetic, operative time, or operative fluid requirements between the two groups. There was a lower rate pressure product in the Epi-GA group during aortic cross clamping (P less than 0.05). More patients in the GA group required a prolonged ventilatory support (P less than 0.05) and a high parenteral narcotic administration (P less than 0.025) during the first 48 hours. While the mortality rate was similar for the two groups (3.0% for GA group vs 5.2% for Epi-GA group), there was a higher percent of postoperative pulmonary complications observed in the GA group (7.6%) compared to the Epi-GA group (2.6%). By facilitating early extubation and a decreased need for systemic narcotics in the early postoperative period, Epi-GA may be beneficial in the high risk pulmonary patient undergoing aortic reconstruction. PMID- 2211799 TI - The management of aneurysms and arterio-venous fistulae of the popliteal artery arising from war trauma. Emphasis on sigmoid operative approach. AB - Between 1986-1988, 600 vascular cases arising from the Iran-Iraq conflict were dealt with within an 18 month period and 60 cases of popliteal artery and/or venous disruption were encountered presenting at variable times after injury. A policy of management between the forward and base hospital surgical teams was introduced, observing the following broad categorizations: (a) assessment/referral, (b) assessment/fasciotomy/referral, (c) immediate operation/referral for further operation/review/management. Two types of incision were used to enter the popliteal fossa: (a) a medial incision and (b) a sigmoid posterior incision (which we now favor). The results of this strategy of management and operative technique (when compared with our previous experience within the same time frame) suggested an improved outcome. Fifty-four out of 60 cases had a satisfactory operative result with below-knee amputation being required in only four cases and higher amputations in two others. No operative or postoperative deaths occurred. The implementation of this "vetting policy" at the front line appeared to reduce the number of amputations and assisted the clarification of management criteria in assessing limb viability at the forward hospital when a large number of casualties were being received. Operative access using the sigmoid posterior incision was not associated with any complications, offered better exposure than the medial incision and was technically easier for the surgeon to perform. PMID- 2211798 TI - Femoral noninfected anastomotic aneurysms. A report of 56 cases. AB - Fifty-six femoral non infected anastomotic false aneurysms (FAAs) were observed in 49 patients admitted to the Institute of Vascular Surgery, University of Milan, from 1975 to 1988; in 6 patients they were bilateral. These aneurysms developed after primary revascularization procedures at a mean interval of 66 months (range 12 to 156 months); one recurred after reparative surgery. Forty four FAAs (78.6%) were asymptomatic, whereas 3 (5.3%) were complicated by acute expansion and 9 (16.1%) by thrombosis. Host vessel degeneration was the cause of aneurysm formation in most cases. A history of hypertension was present in 30% of the patients. All anastomotic aneurysms were operated upon except for one small aneurysm that was asymptomatic. In 5 patients aneurysm resection was carried out on both sides. The surgical technique was endoaneurysmectomy in all the cases with insertion of an interposition graft in 48 cases, a fabric patch in 2 cases and prosthesis re-anastomosis in 5 cases. One case of peripheral embolization occurring in the early postoperative period was successfully treated and there was no operative mortality. In our opinion elective repair of these aneurysms should be recommended whenever possible because of their propensity to develop serious complications and the operative morbidity is low. PMID- 2211800 TI - Selection of antibiotic coverage in vascular patients undergoing cystoscopy. AB - Bacteremic seeding of prosthetic vascular grafts represents a cause for graft infection; transurethral procedures account for one source of bacteremia. Therefore, a prospective study of 200 patients undergoing cystoscopy was conducted to identify the incidence of bacteruria and factors associated with it, organisms involved and their antibiotic sensitivities. Positive cultures were found in 21%. The incidence was 64% in in-patients and 8% in out-patients. Positive cultures were found in 12% of patients who received antibiotics and 29% who did not. Four percent showed signs of bacteremia. The cultures identified both Gram positive and negative organisms; multiple organisms grew in 22%. Gram negative organisms were more common in in-patients. Candida grew in 8%. The Gram positive organisms were sensitive to ampicillin (92%), sulfatrimethoprim (75%) and cefazolin (60%); Gram negative to aminoglycosides (100%) and cefazolin (92%). In view of the unpredictable and multiple organisms, it is recommended that pre cystoscopy cultures be performed and specific antibiotic coverage be based on the sensitivities. PMID- 2211801 TI - Unusual haemostasis for an unusual tumour. Catastrophic bleeding from a tactile neurofibroma affecting the thoracic vertebrae. Case report. AB - The symptomatology of a typical acute descending thoracic aorta dissection was imitated by profuse haemorrhage caused by a benign tumour composed almost exclusively of Wagner-Meissner like tactile corpuscles and fatty tissue. The tumour caused extensive destruction of the bodies of the fifth and sixth thoracic vertebrae at the level of the vertebro-costal articulation. Emergency cross clamping of the descending aorta and haemostasis of the bleeding from osteal defects by tamponade with bone polymethyl methacrylate appeared the only way to control the life threatening haemorrhage. It seems that an intrathoracic tactile neurofibroma with a similar case history has not been reported till now. PMID- 2211802 TI - Spontaneous rupture of an aortic aneurysm into the left renal vein. A diagnostic challenge. AB - Rupture of an aortic aneurysm into a renal vein presents a rare and difficult diagnostic problem. Often, therapy is delayed because the patient is thought to have a urologic problem. In this instance, CT scan provided useful clues leading to the diagnosis of this entity, and its rapid treatment. To our knowledge, this is the first CT scan done in a patient with aorto-renal vein fistula. PMID- 2211803 TI - Plastic bullet arterial embolization following gunshot injury to the heart. Case report and review of the literature. AB - A plastic bullet penetrating the heart through the right ventricle embolized to the right profunda. Suture of the heart and extraction of the bullet resulted in uneventful recovery. The literature revealed 21 instances of embolization following proven heart penetration, in two cases through the right ventricle. PMID- 2211804 TI - Mechanical circulatory support as a bridge to transplantation: current status of total artificial heart in 1989 and determinants of survival. AB - Since April 1986, 40 total artificial hearts (TAH) were implanted as a bridge to transplantation in our institution. In an attempt to identify factors affecting survival of TAH recipients we reviewed our experience over 1000 days of mechanical support. There was no postoperative bleeding requiring surgery nor were there any clinical episodes of thromboembolic complications. Over a total functioning period greater than 3 years there were no mechanical failures in the driving system but one artificial ventricle had to be replaced because of mechanical dysfunction. Infections and multiple organ failure were the primary causes of morbidity and mortality during mechanical support. When the patients who underwent staged transplantation (no. 17) were compared with those who died during mechanical support (no. 23) there were no differences in TAH driving mode or hemodynamic variables between the groups. Although preoperative pulmonary, hepatic and renal functions were found to be similar between the groups, there were significant differences in the early evolution (3 days) of hepatic and renal functions following TAH implant (p less than 0.01). Urinary output was found to be the earliest variable discriminating recovery and survival (p less than 0.01). Finally, univariate analysis indicated age (less than 40 vs greater than 40 years) and modality of cardiac decompensation (acute vs chronic) as the most important factors affecting survival after TAH implantation. Since young patients (less than 40 years of age) with acute decompensation were successfully transplanted in 82% of cases while 100% of older patients with chronic decompensation died before or after transplantation, TAH should be advised in young patients with acute or chronic heart failure and in selected older candidates with recent, acute cardiac failure. PMID- 2211805 TI - Clinical outcome of emergency repeat coronary artery bypass surgery. AB - To determine the clinical outcome of patients requiring emergency repeat coronary artery bypass graft (CABG) procedures, we reviewed 23 such procedures performed for ongoing myocardial ischemia refractory to medical management. The operative mortality was 17%. On follow-up, an average of 24.9 months after emergency reoperation, 14 of the 19 survivors (74%) had recurrent angina. As compared to a randomly selected group of 25 patients who underwent elective repeat CABG procedures during the same time period, the incidence of late cardiac events was significantly higher (79% in the emergency group, 30% in the elective surgery group) and fewer patients had received internal mammary artery (IMA) grafts (9% vs 52%). Emergency repeat CABG operations have considerable operative mortality and poor postoperative functional results with the majority of survivors developing recurrent ischemic syndromes within a short period of time. PMID- 2211806 TI - Primary repair for complete atrioventricular canal: recommendation for early primary repair. AB - Forty patients with complete atrioventricular canal (CAVC) underwent primary repair at Fukuoka Children's Hospital in Fukuoka, Japan, between August 1, 1981 and July 31, 1989. The age at repair ranged from 2 months to 6 years (mean 19 months); weight ranged from 2.3 to 22 kg. The surgical mortality was 2.5%. Justification for early primary repair was examined. Eleven patients underwent repair before 6 months of age (Group 1), 12 patients, between 7 and 11 months of age (Group 2), and 17 patients, after 12 months of age (Group 3). Degenerative changes in the atrioventricular valve increased significantly as age at repair increased (p less than 0.05 Group 1 versus Group 3). The incidence of residual mitral regurgitation tended to increase in the order of Group 1, 2 and 3, though the degree ranged from trivial to mild. Study of the left atrium/aorta ratio by echocardiography revealed that stable values of around 1.1 in Groups 1 and 2 and around 1.3 in Group 3 continued during the follow-up period of 3 years. Assessment of the diameter of the repaired mitral valve in the mean interval of 26 months in groups 1 and 2 revealed normal growth of the mitral valve annulus. The angle between the repaired mitral valve and ventricular septum, which can be affected by the growth of the ventricular septum, converged to normal range in the mean interval of 26 months. Postoperative pulmonary vascular resistance in Groups 2 and 3 was higher at 4.4 +/- 2.3 and 6.3 +/- 2.2, respectively, than in Group 1 at 3.3 +/- 2.2 (p less than 0.01 versus Group 3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2211807 TI - The De Vega tricuspid annuloplasty. Perioperative mortality and long term follow up. AB - One hundred and fifty-three patients undergoing De Vega tricuspid annuloplasty, with or without other associated cardiac procedures between January, 1979, and June, 1987, were evaluated. There were 136 hospital survivors. The follow-up was 98.1% complete for a mean of 3.7 years/patient. Operative mortality was 11.1%; preoperative NYHA class and length of CPB were significant risk factors of perioperative mortality. The actuarial survival of operative survivors at 9 years was 73.5 +/- 11.8%. There were 7 late cardiac deaths among a total of 12 late deaths. Eleven patients required reoperation (2.1 +/- 0.6% patient-year). In seven patients it was necessary for recurrence of tricuspid regurgitation; six of these had also a mitral prosthesis malfunction or a periprosthetic leak. Residual tricuspid regurgitation was judged as mild, moderate or severe in 29.9%, 11.9% and 4.3% of the patients respectively. De Vega tricuspid annuloplasty is the method of choice for mild and moderate tricuspid insufficiency; in selected cases, with a more severe degree of regurgitation, better results could be achieved with a different surgical approach. PMID- 2211808 TI - Cardiac echinococcosis: the diagnostic value of computed tomography scanning. AB - The diagnosis of cardiac hydatid disease is a difficult one. Conventional and specific cardiac investigations are not pathognomonic of this disease. In this report, the diagnostic value of computed tomography (CT) scanning was prospectively investigated in seven patients. In five patients, the diagnosis was confirmed surgically. The CT-information obtained correlated accurately to the operative findings. In all the patients, CT-densities of the lesions were measured and were found to coincide with values of mean CT-densities of hydatid cysts elsewhere in the body. The capability of measuring tissue densities is unique to CT-scanning and have been emphasized in this report. PMID- 2211809 TI - Blunt traumatic pericardial rupture. A ten-year experience 1979 to 1989. AB - Blunt traumatic pericardial rupture is rarely diagnosed preoperatively and is associated with high mortality. During a ten-year period from 1979 to 1989 over 20,000 patients were admitted to a major trauma center and 22 were found to have blunt traumatic pericardial rupture. Sixteen of the 22 (72.7%) were injured in vehicle accidents, 3 (13.6%) in motorcycle crashes, and 2 (9.1%) in falls; 1 (4.5%) was crushed. Eighteen (81.8%) were diagnosed intraoperatively during resuscitation or surgery for associated injuries, and four (18.1%) were diagnosed preoperatively with pericardial window. Eighteen were males and four were females. The median age was 40.14 years (range, 17 to 68). The tears were found at the following sites: left pleuropericardial (14/22 [64%]), diaphragmatic (4/22 [18%]), right pleuropericardial (2/22 [9%]), and superior mediastinal (2/22 [9%]). Associated cardiac injuries were found in only 5 of the 22 (22.7%); all of those patients died. The overall mortality rate was 63.6% (14/22). A high index of suspicion should alert the trauma surgeon to make the diagnosis intraoperatively during emergency surgical resuscitation in the hemodynamically unstable patient and by pericardial window in the stable patient. PMID- 2211810 TI - Disseminated cutaneous herpes zoster following cardiac surgery. AB - Our case report describes disseminated cutaneous Herpes Zoster in the early post operative period following cardiac surgery with cardiopulmonary bypass. This has not been reported previously in the absence of immunosuppressive therapy. Despite associated neurologic and respiratory impairment, our patient was treated successfully with intravenous Acyclovir and subsequently discharged. PMID- 2211811 TI - Right coronary artery injury during tricuspid valve annuloplasty. AB - An unusual complication after tricuspid valve annuloplasty is described where a ring suture ligated right coronary artery and precipitated myocardial infarct and patient death. The need for caution to prevent this complication with such surgery is emphasized. PMID- 2211812 TI - Left ventricular fibroma: echocardiographic diagnosis and successful surgical excision in three cases. AB - The management of three patients with left ventricular fibromas is outlined. All were asymptomatic children. Routine chest radiography suggested cardiac masses. M mode and two-dimensional echocardiography were valuable adjuncts to conventional angiography in assessing these children. Electrocardiographic changes, present in all cases, were shown to regress postoperatively. We stress the importance of these noninvasive aids in the initial investigation and outline our operative methods of reconstruction. PMID- 2211813 TI - Amyloidosis in saphenous vein aortocoronary bypass grafts. AB - A patient in whom idiopathic amyloidosis of aortocoronary saphenous vein grafts was found at autopsy two years after myocardial revascularization due to coronary atherosclerosis is reported. Idiopathic generalized immunocyte derived amyloidosis extensively studied at autopsy was obviously present at the time of surgery although it remained unnoticed macroscopically in the inserted graft. It appears that simultaneously with arterialization further deposition and also significant redistribution of amyloid within the walls of the vein grafts additionally took place after their insertion. It seems interesting that in spite of the amyloidosis the grafts functioned well and were found patent two years after surgery. PMID- 2211814 TI - Antiribophorin antibodies inhibit the targeting to the ER membrane of ribosomes containing nascent secretory polypeptides. AB - Polyclonal antibodies directed against ribophorins I and II, two membrane glycoproteins characteristic of the rough endoplasmic reticulum, inhibit the cotranslational translocation of a secretory protein growth hormone into the lumen of dog pancreas or rat liver microsomes. As expected, site-specific antibodies to epitopes located within the cytoplasmic domain of ribophorin I, but not antibodies to epitopes in the luminal domain of this protein, were effective in inhibiting translocation. Since monovalent Fab fragments were as inhibitory as intact IgG molecules, ribophorins must be closely associated with the translocation site and, therefore, are likely to function at some stage in the translocation process. In all cases, the antibodies that inhibited translocation also caused a significant reduction in total protein synthesis and treatments that neutralized their capacity to inhibit translocation also prevented their inhibitory effect on protein synthesis. This would be expected if the antibodies blocked the membrane-mediated relief of the SRP-induced arrest of polypeptide elongation. The antibodies were effective only when added before translocation was allowed to begin. In this case, they prevented the targeting of active ribosomes containing mRNA and nascent chains to the ER membrane. Thus, ribophorins must either directly participate in targeting or be so close to the targeting site that the antibodies sterically blocked this early phase of the translocation process. PMID- 2211815 TI - Bactenecins, defense polypeptides of bovine neutrophils, are generated from precursor molecules stored in the large granules. AB - Bactenecins are highly cationic polypeptides of bovine neutrophil granules and exert in vitro a potent antimicrobial activity. We have previously purified two bactenecins, designated in an abbreviated form Bac7 and Bac5 from their approximate molecular masses of 7 and 5 kD (Gennaro, R., B. Skerlavaj, and D. Romeo. 1989. Infect. Immun. 57:3142-3146). Here we have studied the biosynthesis, processing, and localization of precursors of Bac7 and Bac5 in bovine bone marrow cells of the myeloid lineage. In vitro translation directed by mRNA isolated from these cells has shown that the primary translation products are preprobactenecins of 23.5 and 21 kD, and are processed to polypeptides of 20 and 15.8 kD, respectively. The 20-kD polypeptide is the granule storage form of Bac7, or proBac7, as also demonstrated by Western blot analysis of lysates of peripheral neutrophils. Between 15 and 50 min from the beginning of its biosynthesis the 15.8-kD polypeptide is converted into the 15-kD granule storage form of Bac5, or proBac5. As shown by immunogold EM, proBac7 and proBac5 are sorted and targeted to the matrix of the so called large granules, which are the predominant organelles in the cytoplasm of bovine neutrophils and are the exclusive store of the nonoxidative antimicrobial system of these cells. Solubilization of granules with Triton X-100 with concomitant unmasking of proteases leads to cleavage of the proforms to Bac7 and Bac5. Experiments performed with protease inhibitors suggest that the proteolytic cleavage is catalyzed in detergent-solubilized neutrophils by neutral serine protease(s), very likely derived from the azurophil granules. PMID- 2211816 TI - Intracellular interactions of transferrin and its receptor during biosynthesis. AB - The interactions between transferrin (Tf) and transferrin receptor (Tfr) as they occur during biosynthesis were studied in the human hepatoma cell line HepG2, which synthesizes both. Early during biosynthesis the Tfr monomer is converted to a disulfide-linked Tfr dimer. The Tfr monomer is not able to bind Tf, but Tf binding is observed as soon as the covalent Tfr dimer is formed and can take place in the ER. The Tf-Tfr complex is transported through the Golgi reticulum and trans-Golgi reticulum (TGR) and is ultimately delivered to an acidic compartment, where Tf releases its Fe3+. We did not observe conversion of Tf to apoTf in the TGR, showing that the part of the TGR passed by secreted Tf has a pH higher than 5.5. We conclude that when a ligand-receptor combination is synthesized by one and the same cell, ligand and receptor can interact during biosynthesis and be transported to the cell surface. PMID- 2211817 TI - Oligomeric structure of the human asialoglycoprotein receptor: nature and stoichiometry of mutual complexes containing H1 and H2 polypeptides assessed by fluorescence photobleaching recovery. AB - The interactions between H1 and H2, the two polypeptides comprising the human asialoglycoprotein receptor (ASGP-R), were investigated by immunofluorescence and lateral mobility measurements combined with antibody-mediated cross-linking and immobilization. Immunofluorescence microscopy revealed two ASGP-R populations on the cell surface, one homogeneously distributed and the other in micropatches. This was observed both in stably transfected NIH 3T3 lines expressing H1 and/or H2, and in the human hepatoma cell line HepG2. In transfected cells expressing both polypeptides (the 1-7-1 line), H1 and H2 were colocalized in the same micro aggregates. Moreover, enhancement of the patching of, e.g., H1 by IgG-mediated crosslinking was accompanied by copatching of H2. To quantify H1-H2 complex formation, the lateral diffusion of H1 and H2 was measured at 12 degrees C (to avoid internalization) by fluorescence photobleaching recovery. H1 (or H2) was immobilized by crosslinking with specific IgG molecules; the other chain was labeled with fluorescent monovalent Fab' fragments, and is lateral mobility was measured. In HepG2 cells, immobilization of either H1 or H2 led to an equal immobilization of the other, indicating that all the mobile H1 and H2 are in stable heterooligomers. In 1-7-1 cells, immobilization of H2 immobilized H1 to the same degree, but immobilization of H1 reduced the mobile fraction of H2 only by 2/3. Thus, in 1-7-1 cells all surface H1 molecules are associated with H2, but 1/3 of the H2 population is independent of H1. From these data and from measurements of the relative surface densities of H1 and H2, conclusions are drawn regarding the oligomeric structure and stoichiometry of the ASGP-R. PMID- 2211818 TI - Predominance of clathrin light chain LCb correlates with the presence of a regulated secretory pathway. AB - Two forms of clathrin light chains, LCa and LCb, are expressed in all mammalian and avian tissues that have been examined, whereas only one type is found in yeast. Regions of structural dissimilarity between LCa and LCb indicate possible functional diversity. To determine how LCa and LCb might differentially influence clathrin function, light chain expression patterns and turnover were investigated. Relative expression levels of the two light chains were determined in cells and tissues with and without a regulated secretory pathway. LCa/LCb ratios ranged from 5:1 to 0.33:1. A higher proportion of LCb was observed in cells and tissues that maintain a regulated pathway of secretion, suggesting a specialized role for the LCb light chain in this process. The ratio of light chains in assembled clathrin was found to reflect the levels of total light chains expressed in the cell, indicating no preferential incorporation into triskelions or coated vesicles. The half-lives of LCa, LCb, and clathrin heavy chain were determined to be 24, 45, and 50 h, respectively. Thus, LCa is turned over independently of the other subunits. However, the half-lives of all three subunits are sufficiently long to allow triskelions to undergo many rounds of endocytosis, minimizing the possibility that turnover contributes to regulation of clathrin function. Rather, differential levels of LCa and LCb expression may influence tissue specific clathrin regulation, as suggested by the predominance of LCb in cells maintaining a regulated secretory pathway. PMID- 2211819 TI - Yeast clathrin has a distinctive light chain that is important for cell growth. AB - The structure and physiologic role of clathrin light chain has been explored by purification of the protein from Saccharomyces cerevisiae, molecular cloning of the gene, and disruption of the chromosomal locus. The single light chain protein from yeast shares many physical properties with the mammalian light chains, in spite of considerable sequence divergence. Within the limited amino acid sequence identity between yeast and mammalian light chains (18% overall), three regions are notable. The carboxy termini of yeast light chain and mammalian light chain LCb are 39% homologous. Yeast light chain contains an amino-terminal region 45% homologous to a domain that is completely conserved among mammalian light chains. Lastly, a possible homolog of the tissue-specific insert of LCb is detected in the yeast gene. Disruption of the yeast gene (CLC1) leads to a slow-growth phenotype similar to that seen in strains that lack clathrin heavy chain. However, light chain gene deletion is not lethal to a strain that cannot sustain a heavy chain gene disruption. Light chain-deficient strains frequently give rise to variants that grow more rapidly but do not express an immunologically related light chain species. These properties suggest that clathrin light chain serves an important role in cell growth that can be compensated in light chain deficient cells. PMID- 2211820 TI - The SPA2 gene of Saccharomyces cerevisiae is important for pheromone-induced morphogenesis and efficient mating. AB - Upon exposure to mating pheromone, Saccharomyces cerevisiae undergoes cellular differentiation to form a morphologically distinct cell called a "shmoo". Double staining experiments revealed that both the SPA2 protein and actin localize to the shmoo tip which is the site of polarized cell growth. Actin concentrates as spots throughout the shmoo projection, while SPA2 localizes as a sharp patch at the shmoo tip. DNA sequence analysis of the SPA2 gene revealed an open reading frame 1,466 codons in length; the predicted protein sequence contains many internal repeats including a nine amino acid sequence that is imperfectly repeated 25 times. Portions of the SPA2 sequence exhibit a low-level similarity to proteins containing coiled-coil structures. Yeast cells containing a large deletion of the SPA2 gene are similar in growth rate to wild-type cells. However, spa2 mutant cells are impaired in their ability to form shmoos upon exposure to mating pheromone, and they do not mate efficiently with other spa2 mutant cells. Thus, we suggest that the SPA2 protein plays a critical role in cellular morphogenesis during mating, perhaps as a cytoskeletal protein. PMID- 2211821 TI - The expression of myosin genes in developing skeletal muscle in the mouse embryo. AB - Using in situ hybridization, we have investigated the temporal sequence of myosin gene expression in the developing skeletal muscle masses of mouse embryos. The probes used were isoform-specific, 35S-labeled antisense cRNAs to the known sarcomeric myosin heavy chain and myosin alkali light chain gene transcripts. Results showed that both cardiac and skeletal myosin heavy chain and myosin light chain mRNAs were first detected between 9 and 10 d post coitum (p.c.) in the myotomes of the most rostral somites. Myosin transcripts appeared in more caudal somites at later stages in a developmental gradient. The earliest myosin heavy chain transcripts detected code for the embryonic skeletal (MHCemb) and beta cardiac (MHC beta) isoforms. Perinatal myosin heavy chain (MHCpn) transcripts begin to accumulate at 10.5 d p.c., which is much earlier than previously reported. At this stage, MHCemb is the major MHC transcript. By 12.5 d p.c., MHCpn and MHCemb mRNAs are present to an equal extent, and by 15.5 d p.c. the MHCpn transcript is the major MHC mRNA detected. Cardiac MHC beta transcripts are always present as a minor component. In contrast, the cardiac MLC1A mRNA is initially more abundant than that encoding the skeletal MLC1F isoform. By 12.5 d p.c. the two MLC mRNAs are present at similar levels, and by 15.5 d p.c., MLC1F is the predominant MLC transcript detected. Transcripts for the ventricular/slow (MLC1V) and another fast skeletal myosin light chain (MLC3F) are not detected in skeletal muscle before 15 d p.c., which marks the beginning of the fetal stage of muscle development. This is the first stage at which we can detect differences in expression of myosin genes between developing muscle fibers. We conclude that, during the development of the myotome and body wall muscles, different myosin genes follow independent patterns of activation and accumulation. The data presented are the first detailed study of myosin gene expression at these early stages of skeletal muscle development. PMID- 2211822 TI - Microinjected centromere [corrected] kinetochore antibodies interfere with chromosome movement in meiotic and mitotic mouse oocytes. AB - Kinetochores may perform several functions at mitosis and meiosis including: (a) directing anaphase chromosome separation, (b) regulating prometaphase alignment of the chromosomes at the spindle equator (congression), and/or (c) capturing and stabilizing microtubules. To explore these functions in vivo, autoimmune sera against the centromere/kinetochore complex are microinjected into mouse oocytes during specific phases of first or second meiosis, or first mitosis. Serum E.K. crossreacts with an 80-kD protein in mouse cells and detects the centromere/kinetochore complex in permeabilized cells or when microinjected into living oocytes. Chromosome separation at anaphase is not blocked when these antibodies are microinjected into unfertilized oocytes naturally arrested at second meiotic metaphase, into eggs at first mitotic metaphase, or into immature oocytes at first meiotic metaphase. Microtubule capture and spindle reformation occur normally in microinjected unfertilized oocytes recovering from cold or microtubule disrupting drugs; the chromosomes segregate correctly after parthenogenetic activation. Prometaphase congression is dramatically influenced when antikinetochore/centromere antibodies are introduced during interphase or in prometaphase-stage meiotic or mitotic eggs. At metaphase, these oocytes have unaligned chromosomes scattered throughout the spindle with several remaining at the poles; anaphase is aberrant and, after division, karyomeres are found in the polar body and oocyte or daughter blastomeres. Neither nonimmune sera, diffuse scleroderma sera, nor sham microinjections affect either meiosis or mitosis. These results suggest that antikinetochore/centromere antibodies produced by CREST patients interfere with chromosome congression at prometaphase in vivo. PMID- 2211823 TI - UV microbeam irradiations of the mitotic spindle. II. Spindle fiber dynamics and force production. AB - Metaphase and anaphase spindles in cultured newt and PtK1 cells were irradiated with a UV microbeam (285 nM), creating areas of reduced birefringence (ARBs) in 3 s that selectively either severed a few fibers or cut across the half spindle. In either case, the birefringence at the polewards edge of the ARB rapidly faded polewards, while it remained fairly constant at the other, kinetochore edge. Shorter astral fibers, however, remained present in the enlarged ARB; presumably these had not been cut by the irradiation. After this enlargement of the ARB, metaphase spindles recovered rapidly as the detached pole moved back towards the chromosomes, reestablishing spindle fibers as the ARB closed; this happened when the ARB cut a few fibers or across the entire half spindle. We never detected elongation of the cut kinetochore fibers. Rather, astral fibers growing from the pole appeared to bridge and then close the ARB, just before the movement of the pole toward the chromosomes. When a second irradiation was directed into the closing ARB, the polewards movement again stopped before it restarted. In all metaphase cells, once the pole had reestablished connection with the chromosomes, the unirradiated half spindle then also shortened to create a smaller symmetrical spindle capable of normal anaphase later. Anaphase cells did not recover this way; the severed pole remained detached but the chromosomes continued a modified form of movement, clumping into a telophase-like group. The results are discussed in terms of controls operating on spindle microtubule stability and mechanisms of mitotic force generation. PMID- 2211824 TI - Injection of anticentromere antibodies in interphase disrupts events required for chromosome movement at mitosis. AB - We have used autoantibodies to probe the function of three human centromere proteins in mitosis. These antibodies recognize three human polypeptides in immunoblots: CENP-A (17 kD), CENP-B (80 kD), and CENP-C (140 kD). Purified anticentromere antibodies (ACA-IgG) disrupt mitosis when introduced into tissue culture cells during interphase. We have identified two execution points for antibody inhibition. Antibodies injected into the nucleus greater than or equal to 3 h before mitosis prevent the chromosomes from undergoing normal prometaphase movements in the subsequent mitosis. Antibodies injected in the nucleus during late G2 cause cells to arrest in metaphase. Surprisingly, antibodies introduced subsequent to the beginning of prophase do not block mitosis. These results suggest that the CENP antigens are involved in two essential interphase events that are required for centromere action in mitosis. These may include centromere assembly coordinate with the replication of alpha-satellite DNA at the end of S phase and the structural maturation of the kinetochore that begins at prophase. PMID- 2211825 TI - Cytoplasmic transport of ribosomal subunits microinjected into the Xenopus laevis oocyte nucleus: a generalized, facilitated process. AB - To study the biochemistry of ribonucleoprotein export from the nucleus, we characterized an in vivo assay in which the cytoplasmic appearance of radiolabeled ribosomal subunits was monitored after their microinjection into Xenopus oocyte nuclei. Denaturing gel electrophoresis and sucrose density gradient sedimentation demonstrated that injected subunits were transported intact. Consistent with the usual subcellular distribution of ribosomes, transport was unidirectional, as subunits injected into the cytoplasm did not enter the nucleus. Transport displayed properties characteristic of a facilitated, energy-dependent process; the rate of export was saturable and transport was completely inhibited either by lowering the temperature or by depleting nuclei of ATP; the effect of lowered temperature was completely reversible. Transport of injected subunits was likely a process associated with the nuclear pore complex, since export was also inhibited by prior or simultaneous injection of wheat germ agglutinin, a lectin known to inhibit active nuclear transport by binding to N-acetyl glucosamine-containing glycoproteins present in the NPC (Hart, G. W., R. S. Haltiwanger, G. D. Holt, and W. G. Kelly. 1989. Annu. Rev. Biochem. 58:841-874). Although GlcNAc modified proteins exist on both the nuclear and cytoplasmic sides of the nuclear pore complex, ribosomal subunit export was inhibited only when wheat germ agglutinin was injected into the nucleus. Finally, we found that ribosomal subunits from yeast and Escherichia coli were efficiently exported from Xenopus oocyte nuclei, suggesting that export of some RNP complexes may be directed by a collective biochemical property rather than by specific macromolecular primary sequences or structures. PMID- 2211827 TI - Cell migration does not produce membrane flow. AB - We have previously reported that rearward migration of surface particles on slowly moving cells is not driven by membrane flow (Sheetz, M. P., S. Turney, H. Qian, and E. L. Elson. 1989. Nature (Lond.). 340:284-288) and recent photobleaching measurements have ruled out any rapid rearward lipid flow (Lee, J., M. Gustafsson, D. E. Magnussen, and K. Jacobson. 1990. Science (Wash. DC.) 247:1229-1233). It was not possible, however, to conclude from those studies that a slower or tank-tread membrane lipid flow does not occur. Therefore, we have used the technology of single particle tracking to examine the movements of diffusing particles on rapidly locomoting fish keratocytes where the membrane current is likely to be greatest. The keratocytes had a smooth lamellipodial surface on which bound Con A-coated gold particles were observed either to track toward the nuclear region (velocity of 0.35 +/- 0.15 micron/s) or to diffuse randomly (apparent diffusion coefficient of [3.5 +/- 2.0] x 10(-10) cm2/s). We detected no systematic drift relative to the cell edge of particles undergoing random diffusion even after the cell had moved many micrometers. The average net particle displacement was 0.01 +/- 2.7% of the cell displacement. These results strongly suggest that neither the motions of membrane proteins driven by the cytoskeleton nor other possible factors produce a bulk flow of membrane lipid. PMID- 2211826 TI - Identification of a multifunctional, cell-binding peptide sequence from the a1(NC1) of type IV collagen. AB - We have previously identified three distinctive amino acid sequences from type IV collagen which specifically bound to heparin and also inhibited the binding of heparin to intact type IV collagen. One of these chemically synthesized domains, peptide Hep-I, has the sequence TAGSCLRKFSTM and originates from the a1(noncollagenous [NC1]) chain of type IV collagen (Koliakos, G. G., K. K. Koliakos, L. T. Furcht, L. A. Reger, and E. C. Tsilibary. 1989. J. Biol. Chem. 264:2313-2323). We describe in this report that this same peptide also bound to intact type IV collagen in solid-phase assays, in a dose-dependent and specific manner. Interactions between peptide Hep-I and type IV collagen in solution resulted in inhibition of the assembly process of this basement membrane glycoprotein. Therefore, peptide Hep-I should represent a major recognition site in type IV collagen when this protein polymerizes to form a network. In addition, solid phase-immobilized peptide Hep-I was able to promote the adhesion and spreading of bovine aortic endothelial cells. When present in solution, peptide Hep-I competed for the binding of these cells to type IV collagen- and NC1 domain coated substrata in a dose-dependent manner. Furthermore, radiolabeled peptide Hep-I in solution also bound to endothelial cells in a dose-dependent and specific manner. The binding of radiolabeled Hep-I to endothelial cells could be inhibited by an excess of unlabeled peptide. Finally, in the presence of heparin or chondroitin/dermatan sulfate glycosaminoglycan side chains, the binding of endothelial cells to peptide Hep-I and NC1 domain-coated substrates was also inhibited. We conclude that peptide Hep-I should have a number of functions. The role of this type IV collagen-derived sequence in such diverse phenomena as self association, heparin binding and cell binding and adhesion makes Hep-I a crucial domain involved in the determination of basement membrane ultrastructure and cellular interactions with type IV collagen-containing matrices. PMID- 2211828 TI - Regulation of proliferation and differentiation of myoblasts derived from adult mouse skeletal muscle by specific isoforms of PDGF. AB - The expression of receptors and the mitogenic response to PDGF by C2 myoblasts, derived from adult mouse skeletal muscle, was investigated. Employing 125I-PDGF binding assays, we showed that the cells exhibit high level binding of PDGF-BB (approximately 165 x 10(3) molecules/cell at saturation) and much lower binding of the PDGF-AA and PDGF-AB (6-12 x 10(3) molecules/cell at saturation). This indicates that the C2 myoblasts express high levels of PDGF receptor beta subunits and low levels of alpha-subunits. PDGF-BB enhances the proliferation of C2 cells maintained in 2% FCS by about fivefold. PDGF-AB had a moderate effect on cell proliferation (less than twofold) and PDGF-AA had no effect. Inverse effects of PDGF isoforms on the frequency of differentiated myoblasts were observed; the frequency of myosin-positive cells was reduced in the presence of PDGF-BB while PDGF-AA and PDGF-AB had no effect. PDGF may thus act to increase the number of myoblasts that participate in muscle regeneration following muscle trauma by stimulating the proliferation and by inhibiting the differentiation of myogenic cells. PMID- 2211829 TI - Carbohydrate binding activities of Bradyrhizobium japonicum. I. Saccharide specific inhibition of homotypic and heterotypic adhesion. AB - Bradyrhizobium japonicum (R110d) exhibited four saccharide-specific binding activities: (a) adsorption to Sepharose beads containing covalently coupled lactose; (b) homotypic agglutination through one pole of the cell (star formation); (c) heterotypic adhesion to the cultured soybean cell line, SB-1; and (d) attachment to roots of soybean plants. Each of these binding activities can be inhibited by the addition of galactose or lactose, but not by derivatives such as N-acetyl-D-galactosamine or melibiose. Treatment of wild-type bacteria with N methyl-N'-nitro-N-nitrosoguanidine followed by selection on the basis of reduced binding to SB-1 cells, resulted in two specific mutants, designated N4 and N6. Compared to wild type, these two mutants also exhibited decreased binding activity in: (a) adsorption to lactose-Sepharose beads; (b) homotypic star formation; and (c) heterotypic attachment to roots of soybeans plants. These results suggest that all four of the saccharide-inhibitable binding activities of Bradyrhizobium japonicum may be mediated by the same mechanism(s) or molecular component(s). PMID- 2211830 TI - Carbohydrate binding activities of Bradyrhizobium japonicum. II. Isolation and characterization of a galactose-specific lectin. AB - Extracts of Bradyrhizobium japonicum were fractionated on Sepharose columns covalently derivatized with lactose. Elution of the material that was specifically bound to the affinity column with lactose yielded a protein of Mr approximately 38,000. Isoelectric focusing of this sample yielded two spots with pI values of 6.4 and 6.8. This protein specifically bound to galactose-containing glycoconjugates, but did not bind either to glucose or mannose. Derivatives of galactose at the C-2 position showed much weaker binding; there was an 18-fold difference in the relative binding affinities of galactose versus N-acetyl-D galactosamine. These results indicate that we have purified a newly identified carbohydrate-binding protein from Bradyrhizobium japonicum, that can exquisitely distinguish galactose from its derivatives at the C-2 position. PMID- 2211831 TI - Correct proteolytic cleavage is required for the cell adhesive function of uvomorulin. AB - All Ca2(+)-dependent cell adhesion molecules are synthesized as precursor polypeptides followed by a series of posttranslational modifications including proteolytic cleavage. The mature proteins are formed intracellularly and transported to the cell surface. For uvomorulin the precursor segment is composed of 129-amino acid residues which are cleaved off to generate the 120-kD mature protein. To elucidate the role of proteolytic processing, we constructed cDNAs encoding mutant uvomorulin that could no longer be processed by endogenous proteolytic enzymes and expressed the mutant polypeptides in L cells. Instead of the recognition sites for endogenous proteases, these mutants contained either a recognition site of serum coagulation factor Xa or a new trypsin cleavage site. The intracellular proteolytic processing of mutant polypeptides was inhibited in both cases. The unprocessed polypeptides were efficiently expressed on the cell surface and had other features in common with mature uvomorulin, such as complex formation with catenins and Ca2(+)-dependent resistance to proteolytic degradation. However, cells expressing unprocessed polypeptides showed no uvomorulin-mediated adhesive function. Treatment of the mutant proteins with the respective proteases results in cleavage of the precursor region and the activation of uvomorulin function. However, other proteases although removing the precursor segment were ineffective in activating the adhesive function. These results indicate that correct processing is required for uvomorulin function and emphasize the importance of the amino-terminal region of mature uvomorulin polypeptide in the molecular mechanism of adhesion. PMID- 2211832 TI - Molecular heterogeneity of basal laminae: isoforms of laminin and collagen IV at the neuromuscular junction and elsewhere. AB - Laminin and collagen IV are components of most basal laminae (BLs). Recently, both have been shown to be products of multigene families. The A, B1, and B2 subunits of the laminin trimer are products of related genes, and the BL components merosin M and s-laminin are homologues of the A and B1 subunits, respectively. Similarly, five related collagen IV chains, alpha 1(IV)-alpha 5(IV), have been described. Here, we used a panel of subunit-specific antibodies to determine the distribution of the laminin and collagen IV isoforms in adult BLs. First, we compared synaptic and extrasynaptic portions of muscle fiber BL, in light of evidence that axonal and muscle membranes interact selectively with synaptic BL during neuromuscular regeneration. S-laminin, laminin A, and collagens alpha 3(IV) and alpha 4(IV) are greatly concentrated in synaptic BL; laminin B1 is apparently absent from synaptic BL; collagens alpha 1(IV) and alpha 2(IV) are less abundant in synaptic than extrasynaptic BL; and laminin B2 and merosin M are present at similar levels synaptically and extrasynaptically. These results reveal widespread differences between synaptic and extrasynaptic BL, and implicate several novel polypeptides as candidate mediators of neuromuscular interactions. Second, we widened our inquiry to assess the composition of several other BLs: endoneurial and perineurial BLs in intramuscular nerves, BLs associated with intramuscular vasculature, and glomerular and tubular BLs in kidney. Of eight BLs studied, at least seven have distinct compositions, and of the nine BL components tested, at least seven have distinct distributions. These results demonstrate a hitherto undescribed degree of heterogeneity among BLs. PMID- 2211835 TI - Abstracts of papers presented at the thirtieth annual meeting of the American Society for Cell Biology. 9-13 December 1990, San Diego, California. PMID- 2211833 TI - Regional and cellular codistribution of interleukin 1 beta and nerve growth factor mRNA in the adult rat brain: possible relationship to the regulation of nerve growth factor synthesis. AB - We have found a regional distribution of IL 1 beta mRNA and IL 1 activity in the normal adult rat brain, which reveals at least partially a colocalization with nerve growth factor (NGF). The predominantly neuronal signal patterns were found over the granule cells of the dentate gyrus, the pyramidal cells of the hippocampus, the granule cells of the cerebellum, the granule and periglomerular cells of the olfactory bulb, and over dispersed cells of the ventromedial hypothalamus and of the frontal cortex. In these areas also the highest levels of IL 1 activity were observed. In the striatum and septum much lower levels of IL 1 beta mRNA and IL 1 activity (shown for the striatum), most likely synthesized by glial cells, could be determined. IL 1 beta-expressing cells were mainly found in brain regions that also synthesize NGF mRNA as shown by in situ hybridization. NGF mRNA could be demonstrated over pyramidal cells of the hippocampus, granule cells of the dentate gyrus, periglomerular cells of the olfactory bulb and over prefrontal cortex neurons. These data indicate that IL 1 beta, among other factors, might also play a regulatory role in the synthesis of NGF in the CNS, as has been demonstrated in the peripheral nervous system (Lindholm, D., R. Heumann, M. Meyer, and H. Thoenen. 1987. Nature (Lond.). 330:658-659). PMID- 2211834 TI - Echistatin is a potent inhibitor of bone resorption in culture. AB - The venom protein, s-echistatin, originally derived from the saw-scaled viper Echis carinatus, was found to be a potent inhibitor of bone resorption by isolated osteoclasts. This Arg24-Gly25-Asp26-(RGD)-containing protein inhibited the excavation of bone slices by rat osteoclasts (IC50 = 0.1 nM). It also inhibited the release of [3H]proline from labeled bone particles by chicken osteoclasts (IC50 = 100 nM). By comparison, the tetrapeptide Arg-Gly-Asp-Ser (RGDS) inhibited resorption by rat or chicken osteoclasts with an IC50 of 0.1 mM while ala24-echistatin was inactive. Video microscopy showed that rat osteoclast attachment to substrate was more sensitive to s-echistatin than was the attachment of mononuclear cells or chicken osteoclasts. The difference in sensitivity of rat and chicken osteoclasts to s-echistatin may be due to differences between receptors on rat and chicken osteoclasts for s-echistatin. Antibody localization of echistatin on these cells showed much greater echistatin binding to rat osteoclasts than to chicken osteoclasts. Laser scanning confocal microscopy after immunohistochemical staining showed that s-echistatin binds to osteoclasts, that s-echistatin receptors are most abundant at the osteoclast/glass interface, and that s-echistatin colocalizes with vinculin. Confocal interference reflection microscopy of osteoclasts incubated with s echistatin, demonstrated colocalization of s-echistatin with the outer edges of clusters of grey contacts at the tips of some lamellipodia. Identification of the echistatin receptor as an integrin was confirmed by colocalization of echistatin fluorescence with staining for an alpha-like subunit. Attachment of bone particles labeled with [3H]proline to chicken osteoclasts confirmed that the mechanism of action of echistatin was to inhibit osteoclast binding to bone presumably by disrupting adhesion structures. These data demonstrate that osteoclasts bind to bone via an RGD-sequence as an obligatory step in bone resorption, that this RGD-binding integrin is at adhesion structures, and that it colocalizes with vinculin and has an alpha-like subunit. PMID- 2211836 TI - Comparison of bone and parathyroid hormone as stimulators of osteoclast development and activity in calvarial cell cultures from normal and osteopetrotic (mi/mi) mice. AB - Osteoclast development was studied in cell cultures prepared from calvaria of neonatal osteopetrotic (mi/mi) mice or their normal littermates, using tartrate resistant acid phosphatase (TRAPase), as an osteoclast marker. In cultures from normal mice, treatment with 10 nM PTH for 4-5 days stimulated the formation of osteoclasts. However in cultures from mi/mi mice, this response was only 7% +/- 5% that of normal mice and they were significantly smaller than osteoclasts of normal mice. Mineralized bone particles elicited osteoclast development in cultures from both normal and mi/mi mice, and osteoclast size was identical for both genotypes. Seventy-eight to 96% of the TRAPase-positive cells bound 125I-CT, as demonstrated by autoradiography. 125I-CT binding characteristics were identical in cultures from both genotypes treated with bone particles, exhibiting a Kd of 3.3-3.6 x 10(-10) M. Addition of PTH stimulated 45Ca release from the added bone particles only in the case of cultures prepared from normal mice, and CT inhibited this response. Cells from normal mice were capable of excavating bone from the surface of smooth cortical bone wafers, but such excavations were rarely seen in the case of calvarial cells from mi/mi mice. Thus, PTH-driven differentiation of osteoclasts is arrested in calvarial cell cultures from mi/mi mice, but mi/mi preosteoclasts retain the ability to express certain osteoclast markers in response to bone derived signals. We hypothesize that the lack of activity of mi/mi osteoclasts is due to the failure of mi/mi preosteoclasts to respond appropriately to resorptive agents, or to cytokines elicited by these agents. PMID- 2211837 TI - Characterization of glutamine transport into resting and concanavalin A stimulated peripheral human lymphocytes. AB - Characteristics of glutamine transport, its substrate specificity, and its pattern of competitive and non-competitive inhibition in response to amino acid analogues were determined in peripheral human lymphocytes, incubated with or without concanavalin A (Con A). Maximum capacity of transport (Vmax) at 37 degrees C and 136.9 mM Na+ was 30 pmol/10(6) cells/30 seconds, while the apparent Km was 142 microM. In cells exposed to 10 mM histidine, asparagine, serine, or leucine transport of glutamine declined to 28%, 15%, 17%, and 21%, respectively, of the rates in controls. Inhibition by histidine (Ki = 0.58 mM) and serine (Ki = 0.25 mM) was competitive, by leucine was non-competitive (Ki = 0.64), while alpha methylamino-isobutyric acid and 2-amino carboxy-bicyclo (2.2.1)-heptane had no effect. In cells cultured for 24 hours with or without 10 micrograms/ml Con A, the apparent Km was 70 microM vs. 89 microM and Vmax 73 vs. 26 pmol/10(6) cells/30 seconds. Sodium depletion (9.0 mM NaCl) greatly diminished glutamine transport in resting and stimulated cells. Inhibition of glutamine transport by serine was sodium sensitive, while inhibition by histidine and asparagine was not. Serine had no competitive effect in sodium-depleted media. The data demonstrate what appear to be two carrier systems for glutamine, sodium sensitive and sodium insensitive. It is suggested that glutamine transport into lymphocytes occurs via processes similar to System N and System ASC described in other cells, with System ASC as the sodium-sensitive component. Con A augments the capacity rather than the affinity of glutamine transporting systems. PMID- 2211838 TI - Thrombospondin gene expression is associated with mitogenesis in 3T3 cells: induction by basic fibroblast growth factor. AB - Growth factor-depleted Swiss 3T3 cells responded to basic fibroblast growth factor (bFGF) with a burst of mitogenesis and with a rapid and marked increase in thrombospondin (TS) mRNA levels. mRNA levels for the alpha 1 chain of type I collagen and for fibronectin were unaffected. At early times following stimulation (0-2 h), "superinduction" of TS mRNA by inhibition of protein synthesis with cycloheximide was not observed, and the increase in TS mRNA could be attributed primarily to an increase in transcription rate of the TS gene. However, at later times (4-8 h) the combination of cycloheximide and bFGF superinduced TS mRNA levels, suggesting the existence of a labile inhibitor of transcription or a short-lived RNase that might be produced in response to prolonged treatment with bFGF. In contrast to its stimulatory effect on 3T3 cells, bFGF did not stimulate the proliferation of mouse muscle BC3H1 cells nor did it cause an increase in TS mRNA levels, but BC3H1 cells do respond to bFGF by inhibition of myogenic differentiation. We propose, on the basis of these and other findings, that TS facilitates the progression of some anchorage-dependent cells through the cell cycle. PMID- 2211839 TI - Effects of differentiation-inducing agents on maturation of human MCF-7 breast cancer cells. AB - The effects of the differentiation inducing agents (DIAS), sodium butyrate (NaBu), retinoic acid (RA), dimethylformamide (DMF), hexamethylene bisacetamide (HMBA), forskolin, and 12-O-tetradecanoylphorbol-13-acetate (TPA), on the growth, morphology, and estrogen receptor (ER) content and epithelial membrane antigen (EMA) expression on a serumless human breast cancer cell line (MCF-7) were compared. All these agents reversibly caused a concentration-dependent growth inhibition in monolayers and markedly reduced colony-forming efficiency in soft agar. A twofold increase in doubling time was obtained with RA (1 microM), but cell replication ceased with NaBu (1 mM), forskolin (50 microM), DMF (1%), HMBA (5 mM), and TPA (8 nM). Total growth arrest induced by these last compounds was preceded by an accumulation of cells in G0/G1 phase observed at 24 h by flow cytometry and accompanied by a change in cell morphology as seen by light and electronic microscopy. An increase in cell volume and the presence of lipid droplets was noted in treated cells that were spread out, as compared with controls. The acquisition of a more mature phenotype was confirmed by an increased expression of EMA monitored by flow cytometry. A specific reduction in the number of ER without any constant dissociation (Kd) modification was also observed after treatment with the 5 DIAs. No modification of morphological or biochemical characteristics, including EMA expression and ER binding, were observed for RA (1 microM)-treated cells. All these results suggest that induction of a more differentiated phenotype is associated with a block in G1 cell cycle phase, resulting in total growth arrest. Apparently, RA (1 microM) treated cells did not fulfill these criteria, since only a slight accumulation in G1 and a slowed growth rate were evaluated. PMID- 2211840 TI - Sarcolectin and interferon in the regulation of cell growth. AB - Sarcolectin is an endolectin present in a great variety of conjunctival tissues (muscles, cartilage, sarcomas), but also in brain or placental extracts of vertebrates, including primates. When purified to electrophoretical homogeneity as a 65-kd protein, it agglutinates cells and has an affinity for simple sugars. In addition, it is able to inhibit the synthesis of interferon (IFN)-dependent secondary proteins and to restore cells to their status ad primum. The biological effect of Poly(I).Poly(C)-induced feedback interferon is inhibited by the addition of sarcolectins, which also abolishes cellular refractoriness to repeated IFN induction. Similarly, sequential association of, first, Poly(I).Poly(C); 4-5 h later, sarcolectin restores the full capacity of both to promote cell growth, unrestrained by IFN. Indeed, the secondary proteins which are in the process of being synthesized are inhibited. In a great variety of animal cells, sarcolectin can also initiate growth after it has been blocked by IFN. This is not an all-or-none effect, but a balance may be struck by IFN and sarcolectin, depending on their respective concentrations and specific activity. We propose that the coordination of these cellular functions of Poly(I).Poly(C), IFN, and sarcolectin takes place in the form of a triangular growth-regulatory cycle and postulate that they thus maintain a balance during differentiated normal tissue development. PMID- 2211841 TI - Role of the Na+/K+/Cl- transporter in the positive inotropic effect of ouabain in cardiac myocytes. AB - In this study we have characterized the bumetanide-sensitive K+/Na+/Cl- cotransport in cultured rat cardiac myocytes. 1) It carries about 10% of the total K+ influx. 2) It is sensitive to furosemide (Ki0.5 = 10(-6)M) and bumetanide (Ki0.5 = 10(-7)M). 3) It is strongly dependent on the extracellular concentrations of Na+ and Cl-. 4) It carries out influx of both ions, K+ and Na+. A therapeutic concentration of ouabain (10(-7) M) stimulated the bumetanide sensitive K+ influx (as measured by 86Rb+), in the cultured myocytes, with no effect on the bumetanide-resistant K+ influx, which was mediated mostly by the Na+/K+ pump. Stimulation of the bumetanide-sensitive Rb+ influx by a low ouabain concentration was strongly dependent on Na+ and Cl- in the extracellular medium. A low concentration of ouabain (10(-7) M) was found to increase the steady-state level of cytosolic Na+ by 15%. This increase was abolished by the addition of bumetanide or furosemide. These findings suggest that ouabain, at a low (10(-7) M) concentration, induced its positive inotropic effect in rat cardiac myocytes by increasing Na+ influx into the cells through the bumetanide-sensitive Na+/K+/Cl- cotransporter. In order to examine this hypothesis, we measured the effect of bumetanide on the increased amplitude of systolic cell motion induced by ouabain. Bumetanide or furosemide, added to cultured cardiac myocytes, inhibited the increased amplitude of systolic cell motion induced by ouabain. Neither bumetanide nor furosemide alone has any significant effect on the basal amplitude of systolic cell motion. We propose that stimulation of bumetanide sensitive Na+ influx plays an essential role in the positive inotropic effect in rat cardiac myocytes induced by low concentration of ouabain. PMID- 2211842 TI - Bumetanide-sensitive Na+/K+/Cl- transporter is stimulated by phorbol ester and different mitogens in quiescent human skin fibroblasts. AB - In this study we investigated the correlation between the mitogenic effect and stimulation of Rb+ (K+) fluxes in human skin fibroblasts treated by purified growth factors. Both K+ transporters, bumetanide-sensitive and ouabain-sensitive, are stimulated 2-3-fold after addition of either fetal calf serum or purified recombinant growth factors to quiescent G0/G1 human skin fibroblasts. Three groups of mitogens were compared: i) the phorbol ester 2-O-tetradecanoyl-phorbol 13-acetate (TPA); ii) growth factors that stimulate inositol phosphate hydrolysis and subsequently activate protein kinase C--fibroblast growth factor (FGF), platelet derived growth factor (PDGF), and alpha-thrombin; and iii) growth factors that do not activate kinase C--insulin-like growth factor-1 (IGF-1), and transforming like growth-factor-alpha (TGF-alpha). The three groups of mitogens stimulated human skin fibroblasts proliferation and Rb+ influxes in a similar dose-dependent fashion. The results indicate that both the bumetanide-sensitive and the ouabain-sensitive Rb+ fluxes are stimulated by protein kinase C-dependent and by the protein kinase C-independent pathways of the mitogenic signal. PMID- 2211843 TI - Biochemical and functional characterization of proteoglycans produced by Sl/Sld murine bone marrow stromal cell lines. AB - The Steel anemia of mice results from an inherited defect in the hematopoietic microenvironment. Proteoglycans synthesized by bone marrow stromal cells are an important functional component of the hematopoietic microenvironment in normal animals. It is thus possible that Steel anemia results from a molecular abnormality involving bone marrow stromal proteoglycans. To investigate this possibility, we studied proteoglycan synthesis in three stromal cell lines from Steel anemic (Sl/Sld) animals and two control stromal cell lines, one (+/+2.4) from a non-anemic littermate, and one (GBl/6) from a normal mouse. Proteoglycans were precursor labelled with 35S sulfate and separated by ion exchange HPLC, CsCl density gradient centrifugation, and molecular sieve HPLC. Glycosaminoglycan (GAG) moieties were characterized by molecular sieve HPLC and enzyme sensitivity. There were no consistent differences in total proteoglycan synthesis, proteoglycan heterogeneity, GAG hydrodynamic size, or enzyme sensitivity among the cell lines studied. Growth factor binding to stromal extracellular matrix (ECM) was studied by co-culture of an IL-3-dependent cell line (FDC-P1) with cell free ECM preparations from an Sl/Sld and a control (GBl/6) stromal cell line, with and without pre-incubation with IL-3. Cell-free ECM preparations from Sl/Sld and control cell lines supported FDC-P1 growth to an approximately equal extent after pre-incubation with IL-3. FDC-P1 growth support by ECM preparations from both cell lines was also observed without IL-3 pre-incubation, although to a lesser extent, suggesting ECM binding of endogenous growth factors synthesized by the stromal cells. PMID- 2211844 TI - Stimulation of fibronectin production by TGF-beta 1 is independent of effects on cell proliferation: the example of bovine adrenocortical cells. AB - We reported previously that transforming growth factor beta (TGF-beta) does not influence the proliferation of bovine adrenocortical cells but is a very potent inhibitor of their steroidogenic functions (Feige et al.: Journal of Biological Chemistry 262:13491-13495, 1987). In the present study, we addressed the question of whether these cells modify the synthesis of their extracellular matrix (in particular of fibronectin) in response to TGF-beta 1, similarly to the changes observed in cell types whose growth is modified by this factor (e.g., fibroblasts). Immunofluorescence studies using anti-fibronectin antibodies revealed that TGF-beta 1 treatment in serum-free medium induced the formation of fibronectin-containing fibrils associated with adrenocortical cells. Metabolic labeling of adrenocortical cells with [35S]-methionine showed that fibronectin synthesis and secretion were highly stimulated by low concentrations of TGF-beta 1. Half-maximal stimulation was observed for TGF-beta 1 concentrations in the range of 0.1 to 0.5 ng/ml and maximal stimulation reached 35-fold over control at the concentration of 2 ng/ml. The earlier detectable effect was observed after 8 h of treatment (6-fold stimulation) and the maximal increase was reached after 24 h of treatment. Stimulation of adrenocortical fibronectin synthesis by TGF-beta 1 appeared to imply a transcriptional event since it was no longer observed in the presence of DRB, a potent inhibitor of RNA polymerases, and because the level of fibronectin mRNA was stimulated under TGF-beta 1 treatment. Taken together, these results indicate that the increased expression of fibronectin is not closely related to growth-regulatory effects of TGF-beta 1 since it is also observed in adrenocortical cells, whose proliferation is unaffected by TGF-beta 1. PMID- 2211846 TI - Modulation of growth and differentiation in normal human keratinocytes by transforming growth factor-beta. AB - The effect of transforming growth factor-type beta 1(TGF-beta) on the growth and differentiation of normal human skin keratinocytes cultured in serum-free medium was investigated. TGF-beta markedly inhibited the growth of keratinocytes at the concentrations greater than 2 ng/ml under low Ca2+ conditions (0.1 mM). Growth inhibition was accompanied by changes in cell functions related to proliferation. Remarkable inhibition of DNA synthesis was demonstrated by the decrease of [3H]thymidine incorporation. The decrease of [3H]thymidine incorporation was observed as early as 3 hr after addition of TGF-beta. TGF-beta also decreased c myc messenger RNA (mRNA) expression 30 min after addition of TGF-beta. This rapid reduction of c-myc mRNA expression by TGF-beta treatment is possibly one of the main factors in the process of TGF-beta-induced growth inhibition of human keratinocytes. Since growth inhibition and induction of differentiation are closely related in human keratinocytes, the growth-inhibitory effect of TGF-beta under high Ca2+ conditions (1.8 mM Ca2+, differentiation-promoting culture environment) was examined. TGF-beta inhibited the growth of keratinocytes under high Ca2+ conditions in the same manner as under low Ca2+ conditions, suggesting that it is a strong growth inhibitor in both low and high Ca2+ environments. The induction of keratinocyte differentiation was evaluated by measuring involucrin expression and cornified envelope formation: TGF-beta at 20 ng/ml increased involucrin expression from 9.3% to 18.8% under high Ca2+ conditions, while it decreased involucrin expression from 7.0% to 3.3% under low Ca2+ conditions. Cornified envelope formation was modulated in a similar way by addition of TGF beta: TGF-beta at 20 ng/ml decreased cornified envelope formation by 53% under low Ca2+ conditions, while it enhanced cornified envelope formation by 30.7% under high Ca2+ conditions. Thus, the effect of TGF-beta on keratinocyte differentiation is Ca2+ dependent. It enhances differentiation of human keratinocytes under high Ca2+ conditions, but inhibits differentiation under low Ca2+ conditions. Taken together, there is a clear discrepancy between TGF-beta effects on growth inhibition and induction of differentiation in human keratinocytes. These data indicate that growth inhibition of human keratinocytes by TGF-beta is direct and not induced by differentiation. PMID- 2211845 TI - Transcellular processing of disulfide- and thioether-linked peroxidase- polylysine conjugates in cultured MDCK epithelial cells. AB - Horseradish peroxidase (HRP) was conjugated to nondegradable polycationic poly(D lysine) (PDL) through either a thioether (HRP-S-PDL) or a disulfide (HRP-SS-PDL) linkage. The binding and transcytosis of these conjugates was studied in Madin Darby canine kidney (MDCK) cell monolayers grown on 3-microns microporous polycarbonate filters. Conjugation of HRP to PDL with both linkages markedly increased the binding of this protein onto the cell monolayers. However, an enhancement of the transcellular transport of HRP in both apical-to-basal and basal-to-apical directions was observed only in HRP-SS-PDL, but not in HRP-S-PDL. HRP-SS-PDL transport was inhibited by colchicine and by 4 degrees C incubation. The transport of 14C-sucrose was not affected by the presence of conjugates. These results indicate that the transport of the conjugate across the cell monolayers was due to a transcellular process rather than to any leakage of the cell junction caused by polycations. The disulfide linkage between HRP and PDL was cleaved rapidly at the basal and, to a lesser extent, at the apical surface of the cell. Neuraminidase treatment decreased the binding of the conjugates onto the cell surface, but did not decrease the transcellular transport, suggesting that not all surface-bound conjugates were available for transcytosis. These results demonstrate that disulfide linkages can be cleaved during transcytosis in MDCK cells. The cleavage, however, occurs mostly at the binding site on the cell surface, which may prevent the cellular uptake of the intact conjugate. PMID- 2211847 TI - Hand injuries in sports and performing arts. PMID- 2211848 TI - Pathophysiology of overuse injuries in the hand and wrist. AB - Injury from overuse is an important and increasingly common problem in athletes and health-conscious people. The unaccustomed application of repetitive stress to any tissue may cause sufficient structural disruption to overcome that tissue's adaptive ability and thus cause injury without necessarily causing complete loss of function. The events leading to injury, as well as the level of stress required to incite them, may vary depending on the tissue and the individual. The pathway common to all tissues most likely involves microdamage to tissue collagen, combined with a direct or indirect effect on the microvasculature, with subsequent oxygen deprivation. The inflammation and repair process common to all tissues is well described. An understanding of this process is critical in the optimal treatment of these injuries. The modification of factors, both intrinsic and extrinsic, is important in the prevention of injury and in a rehabilitation program aimed at return to sports. PMID- 2211849 TI - The epidemiology and prevention of hand and wrist injuries in performing artists. AB - Many performing artists, and especially instrumental musicians, sustain performance-compromising injuries to the wrist and hand. The majority of these are a consequence of overuse as well as of the individual hazards of playing each instrument. An understanding of the specific risk factors of each instrument and of the more general occupational risks of musicians is an invaluable asset in diagnosing, treating, and preventing these career-threatening medical problems. PMID- 2211850 TI - Epidemiology of hand and wrist injuries in sports. AB - Most sports are associated with specific patterns of hand injury. In some cases, these are unavoidable due to the nature of hand involvement dictated by the rules or environment of the sport. In other cases, such injuries point out the need for better protective gear or training. PMID- 2211851 TI - Prevention: conditioning and orthotics. AB - The hand and wrist of both athletes and musicians are very susceptible to injuries. Proper conditioning of the muscles, tendons, ligaments, and joints of the hand and wrist are crucial for injury prevention. Often, orthotic devices, from simple taping to polyethylene casts, can provide adequate protection and support to allow injuries to heal properly or prevent injuries from recurring in susceptible tissues. PMID- 2211852 TI - Analysis of upper-extremity performance in athletes and musicians. AB - Injuries can result from direct or indirect trauma and overuse in sports and the performing arts. These injuries occur when the objective exceeds the physiologic tolerance. Biomechanics analysis enables the estimation of the capacities of the body as well as the loading environment encountered by the tendons, muscles, bones, and joints during various types of sports and musical activities. PMID- 2211853 TI - Evaluation and treatment of hand and wrist disorders in musicians. AB - Hand symptoms in musicians reflect a complex, multifactorial etiology. A multidisciplinary approach is required for proper evaluation and treatment. Good results can be achieved in most patients with localized inflammatory and overuse disorders or nerve compression syndromes. Motor control disorders and chronic pain syndromes are associated with poorer results. Early diagnosis appears to improve outcome. PMID- 2211854 TI - Occupational hand cramps: professional disorders of motor control. AB - Occupational cramps affecting the upper extremities have been described for centuries, though only recently is light being shed on their pathogenesis, pathophysiology, and improved strategies for diagnosis and treatment. These dystonias represent localized stereotyped painless movement disorders affecting certain occupational groups in characteristic ways. We retrospectively reviewed 65 patients given a diagnosis of focal dystonias of the upper extremity and describe painless manual incoordination syndromes, insidious in onset, without objective sensory abnormalities, precipitated by certain repetitive actions of the upper extremity. This confirms previous clinical reports. Pathogenesis and pathophysiology are still uncertain, but evidence for altered higher order (basal ganglia and cortical) influences on spinal interneurons leading to ill-directed motor output is hypothesized. Therapeutic options are reviewed stressing the inadequacy of any one mode discovered to date. PMID- 2211855 TI - Sport-related fractures and dislocations in the hand. AB - The long-term prognosis regarding any sport-related injury should remain guarded. Although optimism may be expressed by the physician regarding a specific injury, the athlete must be adequately informed of the natural history of his or her injury. The hand surgeon's management efforts must always be exact and appropriate, but the athlete must understand from the outset that the final functional and cosmetic result may depend more on the nature of the specific injury than on the treatment provided. PMID- 2211856 TI - Neurovascular injuries in the hands of athletes. AB - Neurovascular injuries are rare in the athlete. Prevention is the ultimate goal. Modification of protective devices, alteration of technique, and education may help avoid some of the neurovascular problems described in this article. Early recognition and appropriate conservative treatment may alleviate the need for surgical intervention. PMID- 2211857 TI - Tendinitis, overuse syndromes, and tendon injuries. AB - Tendinitis and overuse syndromes plague athletes and performing artists. Although rarely career ending, both may impair performance for significant periods of time. This article emphasizes the distinction between these two entities and discusses proper diagnosis and treatment. PMID- 2211858 TI - Fractures and ligamentous injuries of the wrist. AB - Rapid diagnosis, appropriate management, and sport-specific rehabilitation are important in the management of any wrist injury in the athlete. The addition of technetium scans, CT, arthroscopy, and MRI in the evaluation of the athlete's wrist has provided valuable and powerful diagnostic tools. The versatility and relatively low invasiveness of arthroscopic intervention and the subsequent early return to activity make this technique especially attractive in the high performance athlete. Suspicion of potential injuries, complete knowledge of wrist mechanics and anatomy, and a careful physical examination are still the most important tools in the evaluation of wrist injury. It is important to approach each athlete in a patient-oriented manner, taking into account the fact that many of these injuries have the potential to be career ending. Treatment that will provide the best possible long-term wrist function must be the physician's ultimate goal. In addition, the importance of appropriate and activity-specific rehabilitation cannot be overemphasized. PMID- 2211859 TI - Gymnast's wrist. AB - The wrist is a frequent site of symptoms and injury in the gymnast, both acute and chronic. The chronic injuries are due to repetitive loading of the musculoskeletal system, and their incidence rises as participation and level of competition rises. More attention needs to be directed toward prevention, but many of these injuries seem to be inherent to the sport as it transforms the upper extremities into weight-bearing limbs. Evaluation and recognition of wrist injuries in the gymnast will allow appropriate management for these patients; however, the compulsive and intense nature of many gymnasts can lead to recurrent or new injury and continued wrist symptoms. Much more sophisticated and detailed examination of the gymnast's wrist should be done before onset of training, before increase of intensity of training, before competition, and with the onset of any symptoms, including observed guarding. In addition, pretraining and annual follow-up wrist radiographs should be considered for the skeletally immature gymnast. Follow-up evaluation after skeletal maturity and retirement from active participation is needed to elucidate the long-term effect of gymnastics on the wrist. PMID- 2211861 TI - Upper-extremity rehabilitation: conditioning and orthotics for the athlete and performing artist. AB - Rehabilitation of athletes or musicians with hand injuries begins immediately after injury. Accurate diagnosis of the injury and tissues involved is followed by specific acute and rehabilitative therapies to correct the injury and determine any biomechanical changes that may have occurred. Medication and physical methods aid in decreasing inflammation and pain. Mobility is progressively restored, with the aid of appropriate heating modalities, as soon as signs and symptoms allow. Proprioception and neuromuscular coordination are then retrained. This is followed by balanced muscle strength training. Finally, sport-specific endurance and biomechanical skills are developed. Emotional aspects of the injury may be dealt with by investigating the physical and emotional stresses of the performance, and discussing them with the patient. Some patients may also be helped by psychologic counseling. Orthotics may be used to decrease swelling, decrease pain, and inhibit unwanted motion. Some variations allow for progressive range of motion and strength building. Attention to these details maximizes the chances of successful return to performance in the athlete or performing artist with a hand injury. PMID- 2211860 TI - Common disorders of the elbow in athletes and musicians. AB - This article discusses the importance of the elbow in both sports and performing arts. Functional, painless motion of the elbow is essential to achieve this end because although most objects of play are controlled by the hand, freedom of movement at the elbow allows one to place the hand in space. Anatomy and biomechanics of the wrist as well as common sports-related injuries are highlighted. In addition, wrist disorders affecting musicians are reviewed. PMID- 2211863 TI - How mobile are active RNA polymerases? PMID- 2211862 TI - Treatment of musical hands: redesign of the interface. AB - The author discusses comprehensive care of musicians, which requires an understanding of music and the evolution and design of musical instruments. In addition, the clinician must have a working knowledge of limb anatomy and maintenance, musical practice techniques, and the basic principles of hand surgery. PMID- 2211864 TI - Total internal reflection fluorescence (TIRF) microscopy. I. Modelling cell contact region fluorescence. AB - Total Internal Reflection Fluorescence (TIRF) is a powerful technique for visualizing focal and close contacts between the cell and the surface. Practical application of TIRF has been hampered by the lack of straightforward methods to calculate separation distances. The characteristic matrix theory of thin dielectric films was used to develop simple exponential approximations for the fluorescence excited in the cell-substratum contact region during a TIRF experiment. Two types of fluorescence were examined: fluorescently labeled cell membranes, and a fluorescent water-soluble dye. By neglecting the refractive index of the cell membrane, the fluorescence excited in the cell membrane was modelled by a single exponential function while the fluorescence in the membrane/substratum water gap followed a weighted sum of two exponentials. The error associated with neglecting the cell membrane for an incident angle of 70 degrees never exceeded 2.5%, regardless of the cell-substratum separation distance. Comparisons of approximated fluorescence intensities to more exact solutions of the fluorescence integrals for the three-phase model indicated that the approximations are accurate to about 1% for membrane/substratum gap thicknesses of less than 50 nm if the cytoplasmic and water gap refractive indices are known. The intrinsic error of this model in the determination of membrane/substratum separations was 10% as long as the uncertainties in the water gap and cytoplasmic refractive indices were less than 1%. PMID- 2211865 TI - The interaction of Trypanosoma brucei with antibodies to variant surface glycoproteins. AB - Binding to Trypanosoma brucei of polyvalent IgMs and IgGs, monoclonal IgGs and Fab1 fragments of monoclonal IgGs specific for exposed epitopes of T. brucei variant surface glycoproteins (VSGs) was monitored by both immunofluorescence and immunocytochemistry. All antibodies and antibody fragments, were uniformly distributed over the parasite surface after incubation with the organism at 0 degrees C. Upon warming to 37 degrees C bound antibodies and fragments were detected in the flagellar pocket and intracellular organelles. Removal of single layers of bound antibody, or Fab1 fragments, from the cell surface at 37 degrees C, as determined by immunofluorescence, was complete within 20 min and occurred in the presence or absence of protein synthesis. Parasites that had shown an altered distribution of surface-bound antibody after warming remained fully covered with VSGs of the original antigen type as shown by immunocytochemistry. PMID- 2211866 TI - Binding of human endothelium to Ulex europaeus I-coated Dynabeads: application to the isolation of microvascular endothelium. AB - A major problem encountered when isolating human microvascular endothelium is the presence of contaminating cells such as fibroblasts that rapidly over-grow the endothelial cells. We describe here a simple, rapid technique for purifying endothelial cells derived from the microvasculature of neonatal foreskin and osteoarthritic and rheumatoid arthritic synovium. This technique is based on the selective binding of the lectin Ulex europaeus I (UEA I) to the endothelial cell surface via fucose residues. Initially UEA I was covalently bound to tosyl activated super-paramagnetic polystyrene beads (Dynabeads) by incubation for 24 h at room temperature. Cells were isolated by extracting microvascular segments from enzyme-treated (trypsin and Pronase) cubes of tissue. The mixed population of cells obtained were purified by incubating them at 4 degrees C for 10 min with the UEA I-coated Dynabeads. Endothelium bound to the beads whilst contaminating cells were removed by five washes with HBSS using a magnetic particle concentrator. The endothelial cells thus obtained grew to confluence as a cobblestone-like monolayer and expressed von Willebrand factor antigen. The cells were released from the Dynabeads by the competitive binding of fucose (10 min at 4 degrees C). This new method is simple and reproducible and allows pure human microvascular endothelial cells to be cultured within 2 h of obtaining a specimen. PMID- 2211867 TI - Effects of thrombospondin antibody on the recovery of endothelial cells from hyperthermia. AB - In addition to the increased synthesis of the classical heat-shock proteins (28,000, 71,000, 73,000, 90,000 and 100,000 Mr polypeptides) there is also an increase of thrombospondin in the growth medium of endothelial cells exposed to hyperthermia. The effect of a monoclonal antibody to thrombospondin on the recovery of endothelial cells from hyperthermia as it relates to cytoskeletal organization and cell spreading was assessed. The antibody interacts with the heparin-binding domain of thrombospondin in the extracellular matrix of cells. We report that during recovery from thermal insult at 37 degrees C, intermediate filaments, stress fibres and microtubules show distinct time-recovery characteristics in bovine aortic endothelial cells; that in the presence of this antibody the cytoskeleton is notably altered; that this antibody causes retraction of endothelial cell processes; and that the recovery of the cytoskeleton in endothelial cells exposed to hyperthermia is prevented by the thrombospondin antibody in the time frame examined. Our data suggest that the recovery of cells from heat shock requires the integrity of thrombospondin and its interactions. PMID- 2211869 TI - The transition of cells of the fission yeast beta-tubulin mutant nda3-311 as seen by freeze-substitution electron microscopy. Requirement of functional tubulin for spindle pole body duplication. AB - A previous fluorescence light-microscopic study showed that the fission yeast cold-sensitive beta-tubulin mutant nda3-311 was arrested with rod-like condensed chromosomes in a mitotic state at the restrictive temperature. Upon transfer to the permissive temperature, a spindle was formed and the nucleus was divided. In the present study, we employed freeze-substitution electron microscopy to examine the ultrastructure of arrested and released nda3-311 cells. In arrested cells, a single, displaced nucleus was seen with a single spindle pole body. Therefore, spindle pole body duplication seemed to require functional beta-tubulin. The nuclear membrane was highly deformed with a leaf-like profile in cross-section, possibly due to an interaction with the rod-like, condensed chromosomes. Upon transfer to the permissive temperature, the spindle pole duplicated and the daughter spindle pole bodies rapidly migrated to the opposite ends of the nucleus, accompanied by the formation of the mitotic spindle. Elongation of the nuclear envelope occurred with concomitant spindle extension, as in a wild-type mitosis. The deformed nuclear membrane became smooth and described a convex curve. The numerous vacuoles that are seen in the arrested cells decreased in number and increased in size. Septation was completed, leaving the two divided nuclei in one half of the cell. Hexagonally arranged microtubules, apparently forming the mitotic spindle, were observed in a cross-section of a cell after return to the permissive conditions. PMID- 2211868 TI - Growth factors for human fibroblasts in the solute remaining after clot formation. AB - Fibroblasts adhere to, and readily grow into, fibrin clots that form as a result of the cleavage of fibrinogen by thrombin. Subsequent fibroblast replication is believed to be stimulated by mitogens released by entrapped platelets, such as platelet-derived growth factor. We suggest that the supernatant remaining after the fibrinogen-thrombin reaction could stimulate fibroblast replication, even in the absence of other blood components. To examine this hypothesis we expressed liquid from a fibrin clot and measured its mitogenic activity on human lung fibroblasts, in serum-free conditions, using a colorimetric assay based on uptake and subsequent release of Methylene Blue. The clot supernatant caused a mitogenic response of 51 +/- 6% above control and was equivalent to about half that elicited by medium containing 10% newborn calf serum. On their own, both thrombin and fibrinopeptides A and B (small molecular weight cleavage products released from fibrinogen) showed some mitogenic activity, but there was also activity in higher molecular weight cleavage products, suggesting the presence of uncharacterized mitogens. It is proposed that these agents may play important roles in wound healing and diseases associated with vascular leakage and fibrosis, by stimulating fibroblast replication. PMID- 2211870 TI - Spectrin, actin and the structure of the cortical lattice in mammalian cochlear outer hair cells. AB - Mammalian cochlear outer hair cells generate high-frequency forces in response to electrical stimulation. Force generation occurs in the lateral cortex of the cell, which includes the plasma membrane, a two-dimensional 'cortical lattice' of filamentous protein, and a multi-layered membrane system, the lateral cisternae. The cortical lattice is composed of relatively long filaments, 6.7 nm in diameter, which are wound circumferentially about the cell. These filaments are spaced about 42 nm apart and are cross-linked by a second type of filament 3.2 nm in diameter approximately aligned with the longitudinal axis of the cell. The cortical lattice is the only cortical structure that remains after the cell is fully extracted in the detergent Triton X-100 and high-salt solution. It retains the original cylindrical shape of the cell and is reversibly deformable. Antibodies raised against chicken gizzard actin, human blood spectrin and pig brain spectrin all react positively with the extracted lattice viewed using immunofluorescence. Three protein subunits identified in the organ of Corti have approximate molecular weights of 220, 235 and 240K (K = 10(3) Mr) and react with the spectrin antibodies. A structural model of the lattice is proposed in which the circumferential filaments are composed of actin and the cross-linked of spectrin. The model can account for the unusual cylindrical shape of outer hair cells and suggests a mechanism of force generation based upon the elastic and electrostatic properties of spectrin. PMID- 2211872 TI - N-ethylmaleimide-sensitive protein(s) involved in cortical exocytosis in the sea urchin egg: localization to both cortical vesicles and plasma membrane. AB - The exocytotic release of secretory products from fragments of sea urchin egg cortex has been shown to be inhibited by covalent modification of membrane sulfhydryl groups with N-ethylmaleimide (NEM). Exocytotically competent preparations of reconstituted cortex, formed by recombination of purified cortical vesicles (CVs) with fragments of egg plasma membrane (PM) were also inhibited by treatment with NEM. The cellular localization of sulfhydryl containing constituent(s) responsible for inhibition was investigated by treating CVs and/or PM with NEM prior to reconstitution. Both native cortex and cortex reconstituted with NEM-treated components were challenged with calcium-containing buffers. Exocytosis was monitored by phase-contrast microscopy, and quantitated by light scattering. Evidence for CV-PM fusion was obtained with an immunofluorescence-based assay that permits visualization of the transport of CV content proteins across the PM. Cortex reconstituted by recombination of NEM treated CVs with untreated PM or by recombination of untreated CVs with NEM treated PM was exocytotically competent, whereas cortex formed by recombination of NEM-treated CVs with NEM-treated PM was inactive. These results: (1) support the hypothesis that the mechanism of exocytosis in native and reconstituted cortex is the same; (2) provide evidence that both CV and plasma membranes participate in the release of CV contents from reconstituted cortex; and (3) suggest that sulfhydryl-containing protein(s) present on the surface of purified CVs and plasma membrane are involved in exocytosis. PMID- 2211871 TI - Tetrins: polypeptides that form bundled filaments in Tetrahymena. AB - The cortex of the ciliated protozoan Tetrahymena contains a number of fibrous elements, including a network of filaments that pervades the feeding organelle of this organism. The cluster of polypeptides (79-89K; K = 10(3) Mr) in Tetrahymena pyriformis GL-C that constitute these filaments has been purified by in vitro assembly after solubilization in 1.0 M KI. Four distinct sets of these polypeptides, designated 'tetrins', have been shown to be distinguishable from each other by immunochemical and biochemical criteria. The smallest filaments reassembled in vitro were 3-4 nm in diameter and these fine filaments were seen to be bundled together into thicker strands of varying diameters, similar to those within the cell. The thicker filament bundles were clearly distinguishable from intermediate filaments, but fine filaments in these bundles were superficially similar to the 2-5 nm filaments described as microtubule-associated proteins in other organisms. The ultrastructure of the tetrin filaments localized within the feeding organelle reveals a substantial presence of these filaments apart from microtubules. In addition, circular dichroism measurements indicate a relatively low alpha-helical content for these filaments and suggest that the tetrins may be substantially different from other fine filament proteins such as the tektins and giardins. PMID- 2211873 TI - Islands of acetylated histone H4 in polytene chromosomes and their relationship to chromatin packaging and transcriptional activity. AB - The four histones of the nucleosome core particle are all subject to enzyme catalysed, post-translational acetylation at defined lysine residues in their amino-terminal domains. Much circumstantial evidence suggests a role for this process in modifying chromatin structure and function, but detailed mechanisms have not been defined. To facilitate studies on the functional significance of histone acetylation, we have prepared antibodies specific for the acetylated isoforms of histone H4. Because of the extreme evolutionary conservation of H4, these antisera can be applied to a wide variety of organisms and experimental systems. In the present study we have used polytene chromosomes from the salivary glands of larvae of the midge Chironomus to examine the distribution of acetylated H4 in interphase chromatin. By indirect immunofluorescence, antisera to acetylated H4 labeled the four Chironomus chromosomes with reproducible patterns of sharply defined, fluorescent bands. An antiserum to non-acetylated H4 gave a completely different, more-diffuse labelling pattern. Thus, there are defined regions, or islands, in the interphase genome that are enriched in acetylated H4. Double-labelling experiments with two antisera specific for H4 molecules acetylated at different sites, showed that each antiserum gave the same banding pattern. Immunolabelling patterns were not dependent on the pattern of phase-dense bands characteristic of these chromosomes; strongly labelled regions could correspond to phase-dense bands (i.e. condensed chromatin), to interbands or, frequently, to band-interband junctions. Immunogold electron microscopy confirmed the immunofluorescence results and showed further that regions of relatively high labelling could be either transcriptionally active or quiescent, as judged by the presence or absence of ribonucleoprotein particles. Two rapidly transcribed genes on chromosome 4 of Chironomus form characteristic 'puffs', the Balbiani rings BRb and BRc. The antiserum to non-acetylated H4 gave diffuse labelling throughout these puffs, demonstrating the continued presence of this histone in these transcriptionally active regions. Antisera to acetylated H4 strongly labelled the boundaries of BRb and BRc, and revealed clearly defined islands of increased H4 acetylation just within the expanded chromatin of the puffs. Labelling within the central region of each puff was much less intense. A similar pattern was observed in puffs on other chromosomes. Thus, increased H4 acetylation is not found throughout actively transcribed chromatin but occurs only at defined sites, possibly in the non-transcribed flanking regions. H4 acetylation is clearly not required for the passage of RNA polymerase through the nucleosome and we speculate that its role may be to facilitate the binding to DNA of polymerases and other proteins prior to the onset of transcription and possibly replication. PMID- 2211874 TI - Influence of plasma glucose concentration on lumped constant of the deoxyglucose method: effects of hyperglycemia in the rat. AB - The lumped constant of the deoxyglucose method was determined by the steady state, model-independent method in the brain of normal conscious rats with arterial plasma glucose concentrations varying from normoglycemia (i.e., 8 mM) to hyperglycemia (i.e., 31 mM). The lumped constant for brain was found to decrease very gradually with increasing arterial plasma glucose concentration from a value of approximately 0.45 in the midnormoglycemic range (i.e., 7-8 mM) to approximately 0.38 at 28-31 mM. 3-O-[14C]Methylglucose was used to assess the distribution of glucose within the brain structures in hyperglycemia; the results indicated that the glucose concentration, and therefore also the values for the lumped constant, remain relatively uniform in hyperglycemia with arterial plasma glucose concentrations as high as 34 mM. The values for the lumped constant for rat brain determined in the present studies were combined with those previously determined in this laboratory for hypoglycemia and normoglycemia by the same method to provide a single source for the values for the lumped constant to be used over the full range of arterial plasma glucose concentrations. In several rats the lumped constant for cephalic extracerebral tissues was also evaluated in parallel with those for the brain. The lumped constant for the cephalic extracerebral tissues was found to be about twice that for brain and to be unaffected by changes in arterial plasma glucose levels. PMID- 2211875 TI - Regional blood-brain glucose transfer and glucose utilization in chronically hyperglycemic, diabetic rats following acute glycemic normalization. AB - Regional rates of brain glucose utilization (rCMRglc) and glucose influx (rJin), along with regional brain tissue glucose concentrations, were measured in chronically hyperglycemic diabetic (CHD) rats following acute glycemic normalization. These results were compared to those obtained in nondiabetic normoglycemic controls. The diabetic rats were evaluated at 6-8 weeks following i.p. streptozotocin injection. All rats were N2O (70%) sedated, paralyzed, and artificially ventilated for study. Acutely normoglycemic (plasma glucose = 8.5 mumol/ml), demonstrated significantly higher (p less than 0.05) rCMRglc and rJin values in 8 of the 11 regions analyzed. Tissue/plasma glucose concentration ratios were significantly greater than control in 9 of 11 regions. Prior to acute glycemic normalization, rCMRglc values in CHD rats were either unchanged or moderately lower than control. These findings indicate that no blood-brain barrier glucose transport repression is present in CHD rats. In fact, the results suggest an increased transport capacity. The increased rCMRglc observed in the acutely normalized CHD rats may be a manifestation of the "hypoglycemic symptoms" observed in chronically hyperglycemic patients following acute glycemic reductions to the normal range. The present results imply that these symptoms are not related to the presence of a relative cerebral glucopenia, as others have suggested. PMID- 2211876 TI - Angiotensin peptide regulation of fluid-phase endocytosis in brain microvessel endothelial cell monolayers. AB - An in vitro model comprised of primary cultures of brain microvessel endothelial cells was used to investigate angiotensin II (Ang II) effects on blood-brain barrier fluid-phase endocytosis. The effects of Ang II, saralasin, sarathrin, bradykinin (BK), and phorbol myristate acetate (PMA) on brain microvessel endothelial cell fluid-phase endocytosis were determined using the fluorescent marker, Lucifer yellow. Nanomolar concentrations of saralasin (a partial Ang II agonist) stimulated brain microvessel endothelial cell endocytosis by 30% whereas Ang II treatment enhanced Lucifer yellow uptake by 20%. Sarathrin (an Ang II antagonist) had no effect on Lucifer yellow uptake. Nanomolar concentrations of BK and PMA also stimulated Lucifer yellow uptake by the brain microvessel endothelial cell by 40 and 95%, respectively. Stimulatory effects of Ang II and saralasin on Lucifer yellow uptake by brain microvessel endothelial cells could be completely blocked by pretreatment with either sarathrin or indomethacin (an inhibitor of prostaglandin synthesis). In contrast, the effects of neither BK nor PMA on brain microvessel endothelial cell uptake of Lucifer yellow ere altered by indomethacin pretreatment. Results indicated that Ang II, saralasin, BK, and PMA produce similar stimulatory effects on brain microvessel endothelial cell fluid phase endocytosis with only Ang II and saralasin, producing increases in brain microvessel endothelial cell fluid-phase endocytosis that appeared to be mediated by prostaglandins. PMID- 2211877 TI - The time course of intracranial pathophysiological changes following experimental subarachnoid haemorrhage in the rat. AB - The rat subarachnoid haemorrhage (SAH) model was further studied to establish the precise time course of the globally reduced CBF that follows and to ascertain whether temporally related changes in cerebral perfusion pressure (CPP) and intracranial pressure (ICP) take place. Parallel ultrastructural studies were performed upon cerebral arteries and their adjacent perivascular subarachnoid spaces. SAH was induced by a single intracisternal injection of autologous arterial blood. Serial measurements of regional cortical CBF by hydrogen clearance revealed that experimental SAH resulted in an immediate 50% global reduction in cortical flows that persisted for up to 3 h post SAH. At 24 h, flows were still significantly reduced at 85% of control values (p less than 0.05), but by 48 h had regained normal values and were maintained up to 5 days post SAH. ICP rose acutely after haemorrhage to nearly 50 mm Hg with C-type pressure waves being present. ICP then fell slowly, only fully returning to control levels at 72 h. Acute hydrocephalus was observed on autopsy examination of SAH animals but not in controls. Reductions in CPP occurred post SAH, but only in the order of 15%, which could not alone account for the fall in CBF that took place. At 48 and, to a lesser extent, 24 h post SAH, myonecrosis confined largely to smooth muscle cells of the immediately subintimal media was observed. No significant changes in the intima or perivascular nerve plexus were seen. Within 24 h of haemorrhage, a limited degree of phagocytosis of erythrocytes by pial lining cells took place. However, early on the second day post SAH, a dramatic increase in the numbers of subarachnoid macrophages arose from a transformation of cells of the pia arachnoid. This period was characterised by intense phagocytic activity, erythrocytes, fibrin, and other debris being largely cleared over the next 24 h. At 5 days post SAH the subarachnoid macrophage population declined, cells losing their mobile active features to assume a more typical pia-arachnoid cell appearance once more. Our studies indicate that this increasingly utilised small animal model of SAH develops global cortical flow changes only acutely, and it is likely that early vasospasm, secondary to released blood products rather than pressure changes per se, is responsible for the initial cerebral ischaemia that develops. Interestingly, both cerebral arterial vasculopathy and perivascular macrophage phagocytic activity are most marked at approximately 48 h following SAH in the rat, a time at which a phase of delayed cerebral arterial narrowing has previously been documented. PMID- 2211878 TI - The two patterns of reactive astrocytosis in postischemic rat brain. AB - The distribution and time course of postischemic astrocyte hypertrophy and hyperplasia and the relationship to neuronal viability or necrosis was studied in rats subjected to 30 min of carotid and vertebral artery occlusion followed by reperfusion from 3 h to 5 weeks. Intermediate filaments (IFs) were evaluated by electron microscopy, IF proteins by immunohistochemistry, and astrocyte division by [3H]thymidine uptake. Glial fibrillary acidic protein (GFAP) increased in damaged and nondamaged brain regions by 2 days and was associated with cell enlargement, increases in IF, and transformation of GFAP-negative into GFAP positive glia. Cell hypertrophy and increased GFAP persisted only in regions of neuronal necrosis whereas the number and size of GFAP-positive astrocytes returned to control levels in nondamaged regions by 2 weeks. Astrocyte hyperplasia was not seen until 3 days and was confined to damaged brain regions. Vimentin-positive astrocytes were numerous by 2 days in damaged brain and remained only in those regions at 5 weeks. The data demonstrate that reactive astrocytosis develops in undamaged brain, but is reversible with prolonged survival, whereas reactive astrocytosis that accompanies structural brain damage persists for prolonged periods and is associated with hyperplasia, as well as hypertrophy. In addition, the results show that astrocyte expression of vimentin is more specific than GFAP in identifying regions of permanent ischemic injury during the early postischemic period. PMID- 2211879 TI - Time course of postischemic intracellular alkalosis reflects the duration of ischemia. AB - We investigated the long-term (up to 1 week) relationships between the duration of cerebral ischemia and postischemic energy metabolic profile, pH, and tissue edema in the rat. Ten rats each were subjected to 8 or 12 min of forebrain ischemia induced by bicarotid occlusion concurrent with systemic hypotension, and the results were compared with those of 10 sham-operated rat controls. In vivo 31P nuclear magnetic resonance spectroscopy was performed prior to ischemia and at intervals up to 168 h after ischemia. Cerebral edema (measured by specific gravity) was assessed prior to ischemia and at 24, 72, and 168 h after ischemia. The data revealed significant differences in the brain tissue pH profile over time between the ischemic groups (p less than 0.03). The 12-min ischemic animals exhibited brain tissue alkalosis (pH = 7.27 +/- 0.12) at 24 h compared with both sham (pH = 7.09 +/- 0.08) at 24 h and preischemic (pH = 7.06 +/- 0.04) pH values. The pH remained alkalotic (pH = 7.23 +/- 0.15) through the 48-h time period. In contrast, in the 8-min group, the onset of alkalosis was delayed until 48 h after ischemia (pH = 7.24 +/- 0.15), and pH remained alkalotic for only 24 h. No difference in high-energy phosphate metabolism was detected between groups. A different time dependence of tissue pH and specific gravity changes after 12 min of ischemia was detected. The present study suggests that the duration of an ischemic event marks the time of onset of brain tissue alkalosis and its duration and that cerebral edema alone cannot explain the pH changes. PMID- 2211880 TI - Effects of lactacidosis on glial cell volume and viability. AB - Effects of severe lactacidosis were analyzed in vitro by employment of C6 glioma cells and astrocytes from primary culture. The cells were suspended in a physiological medium, which was rendered acidotic by addition of lactic acid in rising concentrations. A pH range of 7.4-4.2 was studied under maintenance of isotonicity and a normal electrolyte concentration of the medium. Cell swelling was quantified by flow cytometry using an advanced Coulter system with hydrodynamic focusing. The method was also utilized for assessment of cell viability by exclusion of the fluorescent dye propidium iodide. The volume of C6 glioma cells was found to increase if the pH was titrated to pH 6.8 or below. From this level downward, the extent of cell swelling depended on the degree of acidosis and the duration of exposure. For example, lactacidosis of pH 6.2 for 60 min led to an increase in cell size to 124.5% of normal, while pH 5.0 or 4.2 led to a cell size of 151.1 or 190.9%, respectively. A comparative analysis of the acidosis-induced cell swelling was made by using sulfuric acid. Swelling of C6 glioma at a given pH was only half of what was found when using lactic acid. This indicates specific swelling-inducing properties of lactic acid, while cell viability was not differently affected by both acids. Of the C6 glioma cells, 89.1% were viable under control conditions at pH 7.4. The viability remained unchanged down to pH 6.2. At pH 5.6, viability remained normal for 30 min, but it decreased to 73.4% after 60 min. Further lowering of pH to 5.0 or 4.6 respectively, decreased the number of viable cells to 47.8 or 40.3%. At pH 4.2 only 21.1% of the cells were surviving 1 h of lactacidosis. Cell swelling from lactacidosis could be largely inhibited by replacement of Na+ and bicarbonate ions in the medium by choline chloride and N-2-hydroxyethylpiperazine-N'-2 ethanesulfonic acid buffer, suggesting an involvement of the Na+/H+ and Cl-/HCO3- antiporters in the swelling process. Omission of Na+ and bicarbonate was, however, associated with reduced viability of the glial cells in acidosis. The swelling response of astrocytes obtained from primary culture was similar to that of C6 glioma. Lactic acid was also more effective in inducing cell swelling than sulfuric acid at the same level of acidosis. In astrocytes, viability at, e.g., pH 5.6 appeared to be more affected by lactic than by sulfuric acid.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2211881 TI - Hippocampal neurons become more vulnerable to glutamate after subcritical hypoxia: an in vitro study. AB - The neurotoxicity of glutamate and hypoxia was investigated in vitro on hippocampal neurons, which were obtained from 18-day-old rat fetuses and were maintained for 3 days in culture. Chemically defined medium without glutamate was used and the plating density was low enough that the effect of exogenously added glutamate could be directly evaluated. In the normal culture condition 1 mM glutamate was necessary to cause significant neuronal loss in the following 24 h. In marked contrast, when glutamate was added after subcritical hypoxic stress, a dose of glutamate as low as 10 microM could exhibit neurotoxicity. Administration of MK-801, a selective noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, could in part reverse this increased susceptibility to low-dose glutamate after hypoxia, although MK-801 could not protect hippocampal neurons from high-dose glutamate. Therefore, both the NMDA receptor and other subclasses of the glutamate receptor may be involved in this neurotoxicity of glutamate. Different mechanisms of glutamate neurotoxicity with high and low doses are discussed. Our results showed that hippocampal neurons exposed to subcritical hypoxia become more vulnerable to glutamate than those without hypoxia. This increased susceptibility is of great interest to understanding the mechanism of slowly ongoing neuronal loss caused by ischemia or epilepsy. PMID- 2211882 TI - MK-801 attenuates capillary bed compression and hypoperfusion following incomplete focal cerebral ischemia. AB - The effects of the N-methyl-D-aspartate (NMDA) antagonist MK-801 on capillary beds and CBF following 1 h of transient incomplete focal cerebral ischemia were studied by examining 133Xe CBF, capillary diameter, and area of perfused vasculature. Capillary diameter increased from a control of 5.24 +/- 0.37 to 8.62 +/- 0.57 microns (p less than 0.001) and area of perfused vasculature from 20,943 +/- 1,151 to 30,442 +/- 1,691 microns2/x 10 magnification field (p less than 0.001) with MK-801 1.0 mg/kg administered 30 min prior to ischemia. After flow restoration in control animals, there was a relative hypoperfusion with eventual normalization of CBF over 60 min. Alternatively, in MK-801 1.0 mg/kg animals, there was rapid normalization of CBF upon flow restoration without the postischemic hypoperfusion observed in controls. On histological analysis, there was consistently less neuronal edema in MK-801-treated animals. These results support the hypothesis that hypoperfusion following incomplete focal cerebral ischemia may be due in part to NMDA-mediated cellular edema with subsequent extravascular capillary bed compression. PMID- 2211883 TI - Nimodipine pretreatment improves cerebral blood flow and reduces brain edema in conscious rats subjected to focal cerebral ischemia. AB - The effect of nimodipine pretreatment on CBF and brain edema was studied in conscious rats subjected to 2.5 h of focal cortical ischemia. An infusion of nimodipine (2 micrograms/kg/min i.v.) or its vehicle, polyethylene glycol 400, was begun 2 h before the ischemic interval and was continued throughout the survival period. Under brief halothane anesthesia, the animals' right middle cerebral and common carotid arteries were permanently occluded, and 2.5 h later, they underwent a quantitative CBF study ([14C]iodoantipyrine autoradiography followed by Quantimet 970 image analysis). Nimodipine treatment improved blood flow to the middle cerebral artery territory without evidence of a "vascular steal" and reduced the volume of the ischemic core (cortex with CBF of less than 25 ml/100 g/min) and accompanying edema by approximately 50% when compared with controls (p = 0.006 and 0.0004, respectively). Mild hypotension induced by nimodipine did not aggravate the ischemic insult. The ischemic core volumes, however, were 50-75% smaller than the 24-h infarct volumes generated in a similar paradigm that demonstrated 20-30% infarct reduction with continuous nimodipine treatment. These results suggest that nimodipine pretreatment attenuates the severity of early focal cerebral ischemia, but that with persistent ischemia, cortex surrounding the ischemic core undergoes progressive infarction and the early benefit of nimodipine treatment is only partly preserved. PMID- 2211884 TI - Microvascular changes during the early phase of experimental bacterial meningitis. AB - We investigated the temporal profile of the changes in regional CBF (rCBF) and intracranial pressure (ICP) during the early phase of pneumococcal meningitis in the rat. rCBF, as measured by laser-Doppler flowmetry, and ICP were continuously monitored during 6 h post infection (p.i.). Brain edema formation was assessed by brain water content determinations. Meningitis was induced by intracisternal injection of 75 microliters of 10(7) colony-forming units/ml pneumococci (n = 7). In control animals (n = 6), saline was injected. There was no change in the rCBF or ICP of controls throughout the experiment. However, there was a dramatic increase in rCBF and ICP associated with brain edema formation in untreated meningitis animals. rCBF increased to 135.3 +/- 33.8% (mean +/- SD) in the untreated animals at 1 h p.i. and reached 211.1 +/- 40.5% at 6 h p.i. (p less than 0.05 compared with controls). ICP increased from 2.9 +/- 1.4 to 10.4 +/- 4.7 mm Hg at 6 h p.i. (p less than 0.05 compared with controls). Brain water content was significantly elevated (79.69 +/- 0.24 compared with 78.94 +/- 0.16% in the control group, p less than 0.05). We investigated the effect of dexamethasone (3 mg/kg i.p.), which was given prior to the induction of meningitis (n = 3) or at 2 h after pneumococcal injection (n = 5), indomethacin (10 mg/kg i.v., n = 5), and superoxide dismutase (SOD; 132,000 U/kg i.v. per 6 h, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2211885 TI - Global energy minimization by rotational energy embedding. AB - Given a sufficiently good empirical potential function for the internal energy of molecules, prediction of the preferred conformations is nearly impossible for large molecules because of the enormous number of local energy minima. Energy embedding has been a promising method for locating extremely good local minima, if not always the global minimum. The algorithm starts by locating a very good local minimum when the molecule is in a high-dimensional Euclidean space, and then it gradually projects down to three dimensions while allowing the molecule to relax its energy throughout the process. Now we present a variation on the method, called rotational energy embedding, where the descent into three dimensions is carried out by a sequence of internal rotations that are the multidimensional generalization of varying torsion angles in three dimensions. The new method avoids certain kinds of difficulties experienced by ordinary energy embedding and enables us to locate conformations very near the native for avian pancreatic polypeptide and apamin, given only their amino acid sequences and a suitable potential function. PMID- 2211886 TI - Computational techniques for vertex partitioning of graphs. AB - A powerful vertex-partitioning algorithm is developed and applied for vertex partitioning of graphs of chemical and spectroscopic interest. The codes developed on the basis of these algorithms are tested and compared for performance with other methods based on the Morgan algorithm and the principal eigenvector algorithm based on the Givens-Householder method. The newly developed algorithm and codes appear to be more powerful than the Morgan and the principal eigenvector algorithms for vertex partitioning of graphs. PMID- 2211887 TI - Automated conformational analysis and structure generation: algorithms for molecular perception. AB - Many methodologies for performing automated conformational analysis require some means of "perceiving" a molecule to determine features of interest. Algorithms for finding rings, bond orders, and stereocenters and detecting the presence of substructural fragments have been developed. These algorithms are described, emphasizing their importance in conformational analysis. PMID- 2211888 TI - [Splenectomy for massive splenomegaly. Apropos of 36 cases]. AB - Thirty-six splenectomies for splenomegaly exceeding 1000 grams are reported. The enlargement of the spleen most often was related with a malignant disease (n = 32). Cytopenia was the main indication in 14 cases, and splenectomy was contemplated for diagnosis (n = 12), initial treatment (n = 6), or due to pain (n = 3) or spontaneous rupture (n = 1). Ten patients (27.8%) had an associated surgical treatment. One patient died postoperatively (2.8%) and 12 patients presented with 14 complications (33%) usually with a rapidly favorable evolution. In 11 of 12 cases (91.6%), the operation allowed establishing the diagnosis in cases of splenomegaly with an unknown origin. Lastly, it was always effective to relieve pain and in most cases improved cytopenia. The authors conclude that the patients with massive splenomegaly are improved by splenectomy, although it most often is merely a palliative treatment in cases of malignant hemopathy. PMID- 2211889 TI - [Results of surgery in 144 cases for aneurysms of the infra-renal abdominal aorta in patients over 75 years of age]. AB - 114 patients aged over 75 underwent surgery for aneurysm of the infra-renal abdominal aorta in the University Teaching Hospitals in Nantes and Angers between 1979 and 1988. A retrospective study of these patients was performed to evaluate the immediate and long-term results. The mean age of the patients was 79 (+/- 4) years, the oldest being 94. 70% were men. Half of the patients underwent emergency or semi-emergency surgery (52 cases). Cardiovascular factors (in particular coronary insufficiency in 17% of cases) were the most common risk factors. In all cases grafting after laying open the aneurysm was performed, with an aorto-aortic graft in 32% of patients, an aorto-iliac graft in 37% or an aorto bifemoral graft in 27% of patients. Combined intestinal revascularisation was performed in 10% of case either involving the inferior mesenteric artery or at least one internal iliac artery; renal revascularisation was performed in 3.5% of cases. 75% of patients underwent simple grafting. The mean duration of hospitalisation was 14 days (+/- 6), including a mean period of 7 days in ICU. 36 patients (31%) died in the first post-operative month. The mortality rate in patients who underwent emergency surgery for a complication of the aneurysm (essentially rupture) was 61% versus 6' for elective surgery. 96% of the patients who survived the first post-operative month were independent at the end of the study or at the time of their death.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2211890 TI - [Abdominal aortic aneurysm detected by a consumption coagulopathy]. AB - Consumption coagulopathy with clinical symptoms reveals aortic arterial aneurysm in less than 5%. Aneurysmal repair with graft is able to remove hemostasis abnormalities for a long time. The physiopathology of these abnormalities is described here through the study of an operated case. It is questionable to use heparinotherapy as exclusive treatment for non operated patients. Heparinotherapy during perioperative period is also a matter of debate. Surgical implications of the consumption coagulopathy are listed: preoperative plasma and platelets transfusions, fibrinogen and antithrombin III perfusions, meticulous hemostasis, minor dissection, use of a women graft. Coagulation disorders disappear before the first postoperative week. Persistent or recurrent consumption coagulopathy invite us to look for a pathological association which often turns out to be a neoplasm. PMID- 2211891 TI - [Nodular thyreopathies. Results of 1300 operations]. AB - To evaluate the results of surgery for nodular thyreopathies, 1300 cases operated on from January 1974 to December 1987 were reviewed. 842 patients (64.7%) were female; the average age, 41 +/- 2.4 year. Thyroid pathology was represented by solitary nodule in 643 cases (49.4%); multinodular goitre in 559 cases (43.0%) (377 euthyroid and 182 hyperthyroid patients); retrosternal in 78 cases (5.9%); recurrent goitre in 20 cases (1.5%). The patients underwent total thyroidectomy (525 cases); sub-total thyroidectomy (132 cases); total lobectomy (643 cases). Post-operative follow-up (clinical exam; T3, T4, tsh analysis); was performed at 3, 6, 12 and 24 months. The overall mortality rate was 0.13 percent (two deaths, respectively after total-0.1% - and sub-total thyroidectomy-0.7%). Immediate post operative complications were: recurrent palsy (9 cases, 0.6%); acute respiratory failure (2 cases, 0.7%); hypoparathyroidism (3 cases, 0.2%). Late sequelae (1-3 year) were recurrent nerve palsy in 7 patients (0.5%); hypoparathyroidism in one case (0.07%). 46 patients which underwent sub-total thyroidectomy were hypothyroid to T3, T4, TSH analysis and required thyroxine support treatment. New concepts on the pathogenesis of multinodular goitre (growth autonomy of goitre human tissue; failure of thyreosuppressive therapy to prevent relapses after sub total thyroidectomy) and the results of this review of 1300 interventions seems confirm the indication to total thyroidectomy in the treatment of both euthyroid and toxic multinodular goitre. PMID- 2211893 TI - [Technic of partial splenectomy with linear stapler instrument (TA 90, U.S., Surgical Corps]. AB - Seven patients have been treated by partial splenectomy, performed with TA 90 linear stapler instrument (U.S. Surgical Corp). Three patients had non parasitic cyst of the spleen, two had malignant disease and two were operated for traumatic injuries. The section and the hemostasis of the spleen was performed with the linear stapler instrument. No patient required blood unit transfusion. Postoperative course was uneventful. Partial splenectomy with the TA 90 stapler, which does not supply the complications of total splenectomy, is an easy and safe procedure. It should be more often indicated. PMID- 2211892 TI - [Presacral cyst of vestigial origin in adults. Problems of diagnosis and therapy]. AB - Concerning one case of cyst developing from embryological remnants in the retro rectal space, the characteristics of these rare tumors are reviewed. The congenital cysts group is formed by teratomas and developmental cysts. Often they are uncovered when they become septic or when they compress adjoining organs. Computed tomography scan has proved valuable in the diagnosis of these lesions. But the precise diagnosis of a congenital cyst can only be made by pathological examination of the specimen after surgical removal. The possibility of malignant degeneration implies the systematic extirpation of any known pre-sacral cyst or tumor. Kraske's trans-sacral approach gives good access to the retro-rectal space. Sometimes, pelvic spread of these lesions requires the use of the abdominal approach. The prognosis for benign tumors is good, but it is poor for malignant tumors. PMID- 2211894 TI - [Cystic pneumatosis of the intestine associated with bronchoemphysema]. PMID- 2211895 TI - [Pneumoperitoneum and gallstones]. PMID- 2211896 TI - [Pseudo-tumoral isolated tuberculosis of the cecum. Apropos of a case disclosed by chronic intestinal obstruction]. PMID- 2211897 TI - [Recurrent pneumothorax after osteosynthesis of the clavicle. Apropos of a case]. PMID- 2211898 TI - Long-chain fatty alcohol quantitation in subfemtomole amounts by gas chromatography-negative ion chemical ionization mass spectrometry. Application to long-chain acyl coenzyme A measurement. AB - We describe a simple and sensitive method to identify and quantitate long-chain fatty alcohols. Long-chain fatty alcohols were converted to their pentafluorobenzoyl derivative and analyzed by gas chromatography (GC)-mass spectrometry in the negative ion chemical ionization (NICI) mode with selected ion monitoring. GC resolution was obtained for myristyl, palmityl, heptadecyl, stearyl, oleyl, linoleyl and arachidonyl alcohols. As little as 0.4 fmol of fatty alcohol can be detected, which represents a six order-of-magnitude increase in sensitivity over previously described methods. This assay can be used to measure femtomolar amounts of long-chain acyl coenzyme A thioesters after reduction to the corresponding fatty alcohols with sodium borohydride. Other potential applications of this assay include identification and quantitation of long-chain fatty alcohol production by microorganisms. PMID- 2211899 TI - Preparative separation of sphingolipids and of individual molecular species by high-performance liquid chromatography and their identification by gas chromatography-mass spectrometry. AB - Six fractions containing tri- to pentaglycosylceramides were isolated from the green, fresh water alga Chlorella kessleri, grown heterotrophically, by using preparative high-performance liquid chromatography (HPLC). Up to twelve fractions were obtained by further reversed-phase HPLC of each glycosylceramide. The use of a polar capillary column with Supelcowax 10 as the stationary phase allowed an excellent separation of the individual molecular species of ceramides, even though the separation did not occur when the ceramides differed only in the position of the amide bond. The individual molecular species (even if present in mixtures) were identified by gas chromatography-chemical ionization mass spectrometry. The evidence for a complete structure was obtained by enzyme splitting with alpha- and beta-galactosidases (the sequence of monosaccharides) and by negative ionization fast atom bombardment mass spectrometry. More than 400 molecular species of glycosylceramides were identified. PMID- 2211900 TI - Separation and indirect detection of small-chain peptides using chromophoric mobile phase additives. AB - Ruthenium(II) 1,10-phenanthroline, Ru(phen)3(2+), and ruthenium(II) 2,2' bipyridyl, Ru(bipy)3(2+), salts were evaluated as mobile phase additives for the liquid chromatographic separation of small-chain peptides on a polystyrene divinylbenzene copolymeric (Hamilton PRP-1) stationary phase. In a basic mobile phase peptides are anions, and retention, resolution and detection occur because of the interactions between the stationary phase, the RuII complex and the peptide anion. Since the RuII complex concentration changes in the analyte band relative to the background eluent RuII complex concentration, the peptide can be detected by indirect photometric detection using the wavelength where the RuII complex absorbs. Peptide analyte peaks may be positive or negative depending on the counter-anion and its concentration. Small-chain peptides that do not contain chromophoric side-chains are detected without derivatization at about 0.1 nmol injected at a 3:1 signal-to-noise ratio. Factors that affect retention, resolution and indirect photometric detection are the RuII complex, its mobile phase concentration, mobile phase pH and solvent composition, and the type and concentration of the mobile phase counter-anion and/or buffer anion. PMID- 2211901 TI - Gas chromatographic and mass spectral determination of aloenin in skin-care cosmetics. PMID- 2211902 TI - Gas chromatographic determination of 2-ethylhexanol and 2-ethylhexanoic acid as derivatives suitable for electron-capture and nitrogen-phosphorus detection after single reaction with heptafluorobutyrylimidazole. PMID- 2211903 TI - Analytical study of phosphorothioate analogues of oligodeoxynucleotides using high-performance liquid chromatography. PMID- 2211904 TI - Direct separation and optimization of timolol enantiomers on a cellulose tris-3,5 dimethylphenylcarbamate high-performance liquid chromatographic chiral stationary phase. AB - A high-performance liquid chromatographic method was developed for the direct resolution and optimization of the separation of timolol enantiomers. The method involves the use of a cellulose tris-3,5-dimethylphenylcarbamate chiral stationary phase (OD-Chiralcel) column. The effects of concentration of 2 propanol, various aliphatic alcohols and diethylamine in the mobile phase and column temperature on the retention and enantioselectivity of timolol enantiomers were studied. The maximum resolution factor obtained was 4.00 when using the solvent system hexane-2-propanol (95:5) containing 0.4% (v/v) diethylamine at 5 degrees C. PMID- 2211905 TI - Ligand-exchange chromatography of alpha-trifluoromethyl-alpha-amino acids on chiral sorbents. AB - The chromatographic behaviour of some alpha-trifluoromethyl-alpha-aminoacids on L proline- and L-hydroxyproline sorbents was studied. The retention and selectivity parameters of the separation of amino acid enantiomers on the sorbents were determined. The introduction of a CF3 [corrected] group led to an increased selectivity in the separation of amino acid enantiomers on a proline sorbent and to a decreased selectivity on a hydroxyproline sorbent. PMID- 2211906 TI - Simultaneous high-performance liquid chromatographic determination of amino acids in a dried blood spot as a neonatal screening test. AB - A new screening test on dried blood spots for inherited disorders of amino acid metabolism using reversed-phase high-performance liquid chromatography (RP-HPLC) is described. The method allows the simultaneous analysis of fourteen different amino acids; among these, seven whose blood levels are increased in the most important amino acid disorders have been determined. The procedure requires a preliminary extraction of the amino acids from 9-mm autoclaved dried blood spots by sonication in phosphate-buffered saline. A precolumn o-phthaldialdehyde-3 mercaptopropionic acid derivatization is then followed by analysis of the amino acids by RP-HPLC. Blood-spots levels of histidine (His), tyrosine (Tyr), valine (Val), methionine (Met), isoleucine (Ile), phenylalanine (Phe) and leucine (Leu) can be determined in a single 15-min run, including column washing and regeneration. The minimum detectable amount of each amino acid is 0.5 pmol with a linear dose-response range between 1 and 10 microM. The recovery for all amino acids is greater than 70% except for Met (66%). Up to 20,000 samples/year can be processed on a single automated analytical line resulting in an estimated cost of about US$ 0.25/sample. The multiple diagnostic capacity, the low cost and the possibility of complete automation of the method make it suitable for primary perinatal screening of amino acid disorders. PMID- 2211907 TI - Bioanalysis of the peptide des-enkephalin-gamma-endorphin. On-line sample pretreatment using membrane dialysis and solid-phase isolation. AB - Des-enkephalin-gamma-endorphin is a neuroleptic endogenous peptide that is active in the central nervous system in extremely low concentrations. The pharmacokinetics of this peptide could not be studied in detail as a bioanalytical method for determining endogenous levels of this peptide in biological matrices was not available. Liquid chromatography with fluorescence reaction detection in principle offers sufficient sensitivity for this application, provided that a selective sample pretreatment can be performed. The development of a pretreatment method for plasma samples is described. After protein precipitation with trichloroacetic acid, high-molecular-weight compounds are removed using on-line continuous-flow dialysis. After dialysis, polar low molecular-weight compounds, including those containing amino functions, are removed by solid-phase isolation, while simultaneously the analyte is concentrated. By means of valve switching the pretreatment system is coupled on line to the liquid chromatographic system. With the developed system it is possible to determine desenkephalin-gamma-endorphin in plasma in the range 10-100 ng/ml. PMID- 2211908 TI - Simultaneous measurement of L-dopa, its metabolites and carbidopa in plasma of parkinsonian patients by improved sample pretreatment and high-performance liquid chromatographic determination. AB - A procedure is described for the determination of L-3,4-dihydroxyphenylalanine (L DOPA), its metabolites and carbidopa (CD) in plasma of Parkinsonian patients by high-performance liquid chromatography with dual working-electrode coulometric electrochemical detection. An efficient sample preparation scheme is presented for the isolation of L-DOPA, its metabolites and the catecholamines from the same plasma aliquot. After a simple deproteinization with methanol containing 2% of 0.5 M perchloric acid and evaporation of the solvent, L-DOPA, its metabolites and CD were separated with a 5-micron Nucleosil C18 column. Catecholamines were extracted from the supernatant of the deproteinized plasma by ion exchange on small columns and adsorption on alumina. Recoveries were close to 100% for L DOPA, its metabolites and CD and 70% for catecholamines. The use of the same mobile phase for the concurrent assay of L-DOPA, its metabolites and catecholamines considerably increased the throughput of samples in the chromatographic system. The dual-electrode coulometric detector afforded peak identification by comparing current ratios. Monitoring of data from patients under L-DOPA therapy is reported. PMID- 2211910 TI - Determination of 4,4'-methylenedianiline in hydrolysed human urine using liquid chromatography with UV detection and peak identification by absorbance ratio. AB - A liquid chromatographic method using multi-wavelength UV detection (258 and 285 nm) is presented for the determination of 4,4'-methylenedianiline (MDA) in hydrolysed human urine. The method is based on hydrolysis under strongly acidic conditions followed by derivatization with pentafluoropropionic anhydride. The perfluoro fatty acid amide derivative formed was analysed on a bonded octadecylsilyl column using isocratic elution with acetonitrile-water (67:33, v/v) as mobile phase. The overall recovery for urine samples containing 115 micrograms/l of MDA was 97 +/- 3%. The calibration graph was linear in the investigated range (12-122 micrograms/l) with a correlation coefficient of 0.998. The precision was 2.3% for urine samples containing 122 micrograms/l and the detection limit was 8 micrograms/l. The chromatograms were evaluated using a combination of retention time data and absorbance ratio by the simultaneous monitoring of the wavelengths 285 and 258 nm. The absorbance ratio (285/258 nm) was virtually constant (0.28 +/- 0.04) in the range 78-10,000 micrograms/l. The precision for the absorbance ratio was 6.1% for urine samples containing 124 micrograms/l and the lowest amount of MDA to give an absorbance ratio was 50 micrograms/l. The procedure for the hydrolysis of urine spiked with MDA and N,N' diacetyl-MDA and urine from skin-exposed workers was studied under strongly acidic, weakly acidic and basic conditions. MDA was found in hydrolysed urines from skin-exposed epoxy resin workers in the concentration range 8-700 micrograms/l. PMID- 2211909 TI - Simultaneous optimization of variables influencing selectivity and elution strength in micellar liquid chromatography. Effect of organic modifier and micelle concentration. AB - Previously, the simultaneous enhancement of separation selectivity with elution strength was reported in micellar liquid chromatography (MLC) using the hybrid eluents of water-organic solvent-micelles. The practical implication of this phenomenon is that better separations can be achieved in shorter analysis times by using the hybrid eluents. Since both micelle concentration and volume fraction of organic modifier influence selectivity and solvent strength, only an investigation of the effects of a simultaneous variation of these parameters will disclose the full separation capability of the method, i.e. the commonly used sequential solvent optimization approach of adjusting the solvent strength first and then improving selectivity in reversed-phase liquid chromatography is inefficient for the case of MLC with the hybrid eluents. This is illustrated in this paper with two examples: the optimization of the selectivity in the separation of a mixture of phenols and the optimization of a resolution-based criterion determined for the separation of a number of amino acids and small peptides. The large number of variables involved in the separation process in MLC necessitates a structured approach in the development of practical applications of this technique. A regular change in retention behavior is observed with the variation of the surfactant concentration and the concentration of organic modifier, which enables a successful prediction of retention times. Consequently interpretive optimization strategies such as the interative regression method are applicable. PMID- 2211911 TI - Neutral, alkaline and difference ultraviolet spectra of secondary metabolites from Penicillium and other fungi, and comparisons to published maxima from gradient high-performance liquid chromatography with diode-array detection. AB - The ultraviolet spectra of 6 predominantly secondary metabolites from filamentous fungi which, inter alia, are useful in the identification of the compounds after chromatography, were obtained in neutral (methanol) and alkaline solvents. Difference spectra were obtained by subtracting the neutral from the alkaline spectrum for each metabolite, using the spectrophotometer software. The data and method are of use in differentiating metabolites with similar chromophores. A database of the maxima was stored on a microcomputer for flexible storage, retrieval and updating of information. These data are compared to those published previously, obtained by diode-array detection using gradient high-performance liquid chromatography, which indicated that changes in solvent concentrations of the gradient affect the spectra of some metabolites. This could cause misidentification of chemosyndromes and metabolites which have been claimed to be of use in fungal chemotaxonomy. PMID- 2211912 TI - Ion chromatographic determination of plasma oxalate in healthy subjects, in patients with chronic renal failure and in cases of hyperoxaluric syndromes. AB - An ion chromatographic procedure for the determination of plasma oxalate is proposed, in which the ultrafiltered sample is injected into an ion chromatographic system. Sample processing appears effective in avoiding spontaneous oxalogenesis. Sensitivity (down to 1.0 mumol/l) allows determinations in normal and pathological samples; recoveries from plasma ultrafiltration are 94.6 +/- 11.7%. Protein binding was investigated and precautions to improve recoveries from plasma ultrafiltration are proposed. The technique is simple to perform from healthy controls averaged 6.75 +/- 2.62 mumols/l (mean +/- S.D. n = 18); samples from patients with primary hyperoxaluria and chronic renal failure undergoing regular dialysis were also analysed and some of the data obtained are reported and discussed. PMID- 2211913 TI - High-performance liquid chromatographic investigation of the interaction of phenylmercuric nitrate and sodium metabisulphite in eye drop formulations. AB - The degradation of phenylmercuric nitrate in the presence of sodium metabisulphite in eye drop formulations has been investigated using a stability indicating high-performance liquid chromatographic (HPLC) method. HPLC methods have been developed for the quantitation of the principal degradation products (diphenyl-mercury, benzenesulphonic acid and benzenesulphinic acid) and a mechanism is proposed for their formation. The pharmaceutical significance of the interaction is briefly discussed. PMID- 2211914 TI - Identification of exposure markers in smokers' breath. AB - Volatile organic compounds present in the exhaled breath of 26 smokers and 43 non smokers were evaluated in an effort to identify possible biochemical markers resulting from the exposure to cigarette smoke. The total ion current profiles obtained from gas chromatography-mass spectrometry (GC-MS), which contained about 230 GC-MS peaks, were first analyzed by using standard statistical procedures to select a subset of 22 peaks. The importance of the peaks was ranked using factor analysis, which further reduced the dimensionality of the data, and discriminant analysis served to develop classification functions. One peak, 2,5-dimethyl furan, had sufficient discriminatory power in the GC-MS profiles to allow almost complete differentiation (96% correct classification) between the smokers and non smokers groups. In addition, several other compounds were able to separate the groups with a high level of accuracy. PMID- 2211915 TI - Determination of hydrazine in hydralazine by capillary gas chromatography with nitrogen-selective detection after benzaldehyde derivatization. AB - A method for the determination of hydralazine substance is described. Hydrazine is derivatized in aqueous media with benzaldehyde to benzalazine. After extraction to an organic phase containing a homologue as marker, the sample is subjected to capillary column gas chromatography with nitrogen-selective detection. A prolonged reaction with 0.1 M benzaldehyde of 20 min or more led to an increased level of benzalazine when hydralazine was analysed. An increase was also observed if the aqueous hydralazine sample had been allowed to stand for some time before analysis. The final method involved the use of a 5-min reaction time, fresh solutions and the standard addition principle. The levels of hydrazine found in hydralazine hydrochloride were below 1 ppm (as bases, 1 ng/mg). PMID- 2211916 TI - Electric properties of photoaffinity-labelled pancreatic A-subtype cholecystokinin. AB - Although the isoelectric point of a protein is very important, electric focusing of intrinsic membrane proteins in polyacrylamide or agarose gels often fails. The recently introduced Bio-Rad Rotofor cell allowed isoelectric focusing of such a protein, cholecystokinin (CCK) receptor. Both the isoelectric point and the molecular weight (Mr) of pancreatic CCK receptor were determined. For this purpose, membrane CCK receptor was photoaffinity labelled by a cleavable agonist probe, subsequently prepurified on immobilized wheat germ agglutinin and analysed by sodium dodecyl sulphate polyacrylamide gel electrophoresis and isoelectrofocusing in solution in the presence of Nonidet P-40. CCK receptor was identified at Mr 85,000-100,000, whereas its deglycosylated product was shifted to Mr 42,000. Further, the isoelectric points of the glycosylated and deglycosylated forms of CCK receptor were pH 4.8 and 4.3, respectively. A knowledge of the isoelectric point should help in characterizing better CCK receptor heterogeneity and/or in purifying CCK receptor proteins. PMID- 2211918 TI - Determination of flavins in dairy products by high-performance liquid chromatography using sorboflavin as internal standard. PMID- 2211917 TI - Hadamard transform photothermal deflection densitometry of electrophoretically blotted proteins. AB - Hadamard transform spatial multiplexing techniques are applied to laser densitometry in order to prevent the photo-induced degradation of sensitive materials. Photochemical and thermal degradations can often occur in point focused scanning laser densitometry. In spatial multiplexing, the excitation source is defocused and efficiently distributed throughout the sample, reducing local power density. In this paper, we describe the application of Hadamard transform spatial multiplexing to transverse photothermal deflection spectroscopy (PDS). Proteins western blotted on nitrocellulose membrane are line imaged using the Hadamard transform PDS densitometer. For comparison, the blots are imaged with a high-dynamic-range video densitometer. PMID- 2211919 TI - Determination of 10-camphorsulphonates in pharmaceutical formulations by high performance liquid chromatography. PMID- 2211920 TI - Influence of pressure on the maximum production rate in preparative liquid chromatography. PMID- 2211921 TI - Analytical and preparative resolution of enantiomers of prostaglandin precursors and prostaglandins by liquid chromatography on derivatized cellulose chiral stationary phases. AB - Analytical methods were developed for the separation of the enantiomers of four cyclopentenone precursors of prostaglandins. The resolution obtained is correlated with the chemical environment around the chiral center of the cyclopentenones. The analytical methods were scaled up to preparative loadings and the chromatographic parameters were varied to determine their effect on the preparative separations. The correlation between analytical resolution and preparative resolution was also investigated. In addition to the precursors, the preparative resolution of the enantiomers of a synthetic prostaglandin analogue was investigated. PMID- 2211922 TI - Determination of dexamethasone in bovine tissues by coupled-column normal-phase high-performance liquid chromatography and capillary gas chromatography-mass spectrometry. AB - A new method for the determination of dexamethasone in bovine liver and muscle tissues has been developed. Crude tissue extracts were obtained by means of a three-phase liquid-liquid extraction scheme. The resulting residue was subjected to coupled-column normal-phase high-performance liquid chromatography which served to isolate the drug for the purpose of screening and quantification. Sample was injected onto the first column of the system, a phenyl column, from which a heart-cut was diverted to a short silica column which retained dexamethasone. The contents of this column were backflushed onto a cyanopropyl column which isolated dexamethasone. Mobile phases consisted of hexane modified with 2-propanol, acetic acid, and water. Analysis of each sample was completed in 15 min. Quantitation was performed by external standard calibration of ultraviolet response at 239 nm. Limits of detection were estimated to be 4 and 6 ppb in muscle and liver, respectively. In addition to screening and quantitation, the coupled-column system purified tissue extracts for gas chromatographic-mass spectrometric analysis which, in the selected-ion monitoring mode, confirmed the identity of the trimethylsilyl-enol-trimethylsilyl derivative of dexamethasone. PMID- 2211924 TI - Determination of benzydamine and its N-oxide in biological fluids by high performance liquid chromatography. AB - A simple, sensitive and selective method for the determination of benzydamine in human plasma and urine, and for benzydamine N-oxide in urine, has been developed using high-performance liquid chromatography in the reversed-phase mode. The limit of reliable determination of benzydamine in plasma was 0.5 ng/ml and that in urine 1 ng/ml; the limit of reliable determination of benzydamine N-oxide in urine was 50 ng/ml. The method has been successfully applied to the analysis of these compounds in biological fluids after administration of intravenous and oral doses of benzydamine to human volunteers. PMID- 2211923 TI - Gas chromatographic-electron-impact mass fragmentometric determination of lysergic acid diethylamide in urine. AB - A sensitive method for the detection and quantitation of lysergic acid diethylamide (LSD) in urine was developed. After initial solvent extraction, the compound was further purified by liquid-liquid extraction or by solid-phase extraction. The trimethylsilyl derivative of LSD was detected by gas chromatography-mass spectrometry (GC-MS) operated in the electron-impact mode with selected-ion monitoring. The presence of LSD was confirmed by comparing retention times and relative abundances of ions of unknowns with that of a standard. The recovery of this procedure was greater than 89%. The intra-run and inter-run coefficients of variation were less than 5% and less than 7%, respectively. This procedure allows detection of LSD concentrations as low as 29 pg/ml. Quantitation of LSD was linear over the concentration range 50-2000 pg/ml. PMID- 2211925 TI - Simultaneous determination of amino-alpha-carbolines and amino-gamma-carbolines in cigarette smoke condensate by high-performance liquid chromatography. AB - A method for the simultaneous detection of amino-alpha-carbolines (2-amino-alpha carboline and 2-amino-3-methyl-alpha-carboline) and amino-gamma-carbolines (3 amino-1,4-dimethyl-5H-pyrido [4,3-b]indole and 3-amino-1-methyl-5H-pyrido [4,3 b]indole) by high-performance liquid chromatography has been developed. It consists of a three-step purification using three different columns with fluorometric detection. With this method, we have demonstrated that both amino alpha-carbolines and amino-gamma-carbolines are present in cigarette smoke condensate. The method may be useful for detecting these carcinogens in various materials. PMID- 2211926 TI - High-performance liquid chromatographic method for the analysis of 10-ethyl-10 deaza-aminopterin and metabolites in plasma. AB - 10-Ethyl-10-deaza-aminopterin (10-EdAM) is a novel folic acid antimetabolite currently being tested in phase II clinical trials. We have developed an isocratic high-performance liquid chromatographic method for the quantification of 10-EdAM and metabolites in plasma. Solid-phase extraction was used for sample clean-up. Adequate accuracy was obtained without the use of an internal standard. Fluorometric detection with excitation at 243 nm and emission at 488 nm was used for accurate quantification of samples containing small amounts of drug or metabolites (2.0-4.0 nM, depending on the compound). Ultraviolet detection at 350 nm was only applicable for the analysis of plasma concentrations of 10-EdAM exceeding 50 nM. The usefulness of the assay was demonstrated by the results obtained in a pharmacokinetic study. The assay could separate the parent compound from seven identified and two unknown products. PMID- 2211927 TI - Analysis of blood acetate by head-space gas chromatography: comparative studies of reagents for the methyl esterification. PMID- 2211928 TI - Determination of gabapentin in plasma and urine by capillary column gas chromatography. PMID- 2211929 TI - Photodegradation of nifedipine relative to nitrendipine evaluated by liquid and gas chromatography. PMID- 2211931 TI - Detection of tricyclic antidepressants in body fluids by gas chromatography with a surface ionization detector. PMID- 2211930 TI - Simultaneous determination of haloperidol and reduced haloperidol by gas chromatography using a megabore column with electron-capture detection: application to microsomal oxidation of reduced haloperidol. PMID- 2211932 TI - Simultaneous determination of sparteine and its 2-dehydro and 5-dehydro metabolites in urine by high-performance liquid chromatography with electrochemical detection. PMID- 2211933 TI - High-performance liquid chromatographic determination of amiloride and its analogues in rat plasma. PMID- 2211934 TI - Determination of prostaglandins in human seminal fluid by solid-phase extraction, pyridinium dichromate derivatization and high-performance liquid chromatography. AB - Prostaglandins of the E type (PGEs) in human seminal fluid have been determined by reversed-phase high-performance chromatography on a C18 column and ultraviolet detection at 230 nm after solid-phase extraction (C18) and oxidation to the corresponding 15-oxoprostaglandin derivatives by pyridinium dichromate in acetonitrile. Under optimized conditions, PGEs from 10-ml seminal samples were extracted into 4 ml of methyl formate with high recoveries (estimated at greater than 95%) and subsequently separated under mild chromatographic conditions (0.5 mM formic acid-acetonitrile, apparent pH 3.8). Comparable analytical sensitivities were obtained with detection at 230 nm with a conventional deuterium lamp spectrophotometer and a photometer equipped with a cadmium emission source, while with a diode-array spectrophotometer, signal-to-noise ratios were reduced with factors between 4.4 and 3.1, depending on the spectral bandwidth of the instrument. Theoretical aspects of signal-to-noise optimization of ultraviolet detectors are discussed. The stability of dilute standard solutions of PGE2 and PGD2 was measured, showing solutions in dichloromethane at 20 degrees C to be as stable as acetonitrile solutions at 5 degrees C over a period of thirty days. Absolute ethanol and acetonitrile were equally suited as solvents. PMID- 2211935 TI - Simple and sensitive method for monitoring clonazepam in human plasma and urine by high-performance liquid chromatography. PMID- 2211936 TI - High-performance liquid chromatographic determination of etomidate in plasma. PMID- 2211937 TI - Rapid determination of serum levels of a new antifungal agent, fluconazole, by high-performance liquid chromatography. PMID- 2211938 TI - Determination of the serum concentrations of thioridazine and its main metabolites using a solid-phase extraction technique and high-performance liquid chromatography. PMID- 2211939 TI - Determination of marplan in human plasma using high-performance liquid chromatography. PMID- 2211940 TI - Determination of mepamil in human plasma by reversed-phase high-performance liquid chromatography with fluorescence detection. PMID- 2211941 TI - Time-saving method for the reversed-phase high-performance liquid chromatography of phenylthiocarbamylamino acid derivatives of free amino acids in plasma. PMID- 2211942 TI - High-performance liquid chromatographic separation of inositol phosphate isomers employing a reversed-phase column and a micellar mobile phase. AB - Surfactants have been employed in high-performance liquid chromatography (HPLC) for the separation of ionic and non-ionic compounds. We have developed a method employing a reversed-phase column and a mobile phase containing a surfactant, hexadecyltrimethylammonium hydroxide (HDTMA+OH-), for the separation of several inositol phosphate positional isomers. Various parameters were studied for their effect on the chromatographic capacity factor (k'). They included the concentration of HDTMA+OH-, the pH of the bulk micellar suspension and the addition of inorganic salts to the mobile phase. Resolution of the inositol monophosphates was controlled by a mixed mechanism, where the predominant elements were electrostatic forces and the formation of micelles. The elution of the inositol polyphosphate isomers was obtained by increasing the amount of a non polar solvent, in agreement with an ion-pairing process. This method represents an alternative to ion-exchange HPLC. If offers a practical advantage when detection of radiolabeled samples by in-line radioactive flow detectors is required, because low-quenching solvents with good miscibility with scintillant fluids are employed. The analysis of various chromatographic conditions, the system reproducibility and its application to the analysis of biological samples are described. PMID- 2211943 TI - High-performance liquid chromatographic separation and dual competitive binding assay of corrinoids in biological material. AB - Corrinoids were extracted with hot ethanol from human plasma and faeces and separated by high-performance liquid chromatography. The corrinoids (cobalamin and cobalamin analogues) were quantified in the eluted fractions by a dual radioisotope assay using as binders intrinsic factor and haptocorrin to detect cobalamin and total corrinoids, respectively. Recoveries ranged from 37.7 +/- 5.1% for hydroxycobalamin to 75.0 +/- 9.1% for cyanocobalamin. In plasma, the main forms of cobalamin were the coenzymes methylcobalamin and 5' deoxyadenosylcobalamin (32.1 +/- 13.4 and 28.4 +/- 12.3%, respectively, of total corrinoids). The cobalamin analogue fraction of plasma was eluted with a retention time close to that of cobinamide and of deoxyadenosylcobalamin. In the faeces, most of the corrinoids separated were detected better by the haptocorrin assay than by the intrinsic factor assay. One corrinoid peak was eluted with the same retention time as cobinamide. This peak was detected by haptocorrin assay but not by intrinsic factor assay. It could therefore correspond to cobinamide. PMID- 2211944 TI - Plasma and blood assay of xanthine and hypoxanthine by gas chromatography-mass spectrometry: physiological variations in humans. AB - Plasma and blood xanthine and hypoxanthine levels were assayed using a sensitive and specific method involving gas chromatography-mass spectrometry, associated with an optimized sample preparation procedure. Physiological variation was studied in 224 subjects with no purine metabolism disorders. An age dependency for both compounds was found, comparable with that known for uric acid. The mean plasma levels for the 224 subjects were 0.65 +/- 0.24 microM for xanthine and 1.65 +/- 0.78 microM for hypoxanthine. Corresponding mean blood levels were 0.59 +/- 0.21 microM for xanthine and 1.72 +/- 0.74 microM for hypoxanthine. Plasma and blood levels were significantly different, by ca. 10%. Rapid in vitro release of hypoxanthine from erythrocytes and continuation of intraerythrocytal metabolism lead to overestimation exceeding 10% within half an hour after sample blood collection. Hence samples must be deproteinized promptly. Blood can therefore be conveniently used for oxypurine assay instead of plasma when prompt spinning of samples is difficult to manage, as is usually encountered in clinical practice. PMID- 2211945 TI - Quality, appropriateness, and continuous improvement. PMID- 2211946 TI - Education and QA: a model for continuous improvement in skin integrity. PMID- 2211948 TI - Appropriateness of critical care visitation: perceptions of patients, families, nurses, and physicians. PMID- 2211947 TI - A client satisfaction survey in home health care. PMID- 2211949 TI - Patient education and continuous improvement in a phase 1 cardiac rehabilitation program. PMID- 2211950 TI - Occurrence screening: a program for improving quality and appropriateness of care. PMID- 2211951 TI - Evaluating quality and ongoing improvement of clinical practice following HIV/AIDS education. AB - a comprehensive effort to improve quality and appropriateness of care in a large teaching hospital has been planned and implemented. Fuel for the initiative was gleaned from the combined energies of QA education, infection control, and administration. Challenges for continuous improvement of care for persons who are HIV positive are being anticipated through educational interventions and a program of ongoing evaluation. In concert, movement is toward a safer, more compassionate, cost-effective, and clearly communicated approach to care for patients with HIV/AIDS. PMID- 2211952 TI - Improving compliance with universal blood and body fluid precautions in a rural medical center. PMID- 2211954 TI - Collaborating on a quality of care study. PMID- 2211953 TI - Patient perception of hospitalization as an avenue to change. PMID- 2211955 TI - Marketing QA: a new management strategy to improve staff participation and commitment. PMID- 2211957 TI - Inoculation of sugar beet protoplasts with beet necrotic yellow vein virus particles by mild sonication. AB - A novel procedure employing mild sonication for in vitro inoculation of plant protoplasts with virus particles has been established. Sugar beet (Beta vulgaris L.) protoplasts were briefly exposed to 20 kHz ultrasound in the presence of beet necrotic yellow vein virus (BNYVV) particles. The accumulation of BNYVV coat protein was analyzed by an enzyme-linked immunosorbent assay. The infection was detectable after 16 h and reached maximum 3-3 1/2 days after inoculation. Maximum levels of BNYVV coat protein in inoculated protoplasts were obtained by sonication for 500-600 ms at 45-60 W. This reduced the viability to 15-30%. The efficiency of the inoculation increased with the concentration of BNYVV particles up to 28 micrograms/ml. Infection was found to be optimal when the BNYVV particles were added just before sonication but low levels of infection could be obtained by addition of virus particles up to 60 min after sonication. PMID- 2211956 TI - Removal of HIV antigens and HIV-infected cells in vitro using immunomagnetic beads. AB - Human anti-HIV antibody-coated magnetic beads and magnetic particle concentrators were used to eliminate HIV antigens and the infected cells in vitro. Fifty micrograms/ml of the antibody coated on 30 mg/ml of tosyl-activated beads, and 10 min of reaction time between the antigens and the immunobeads were sufficient to eliminate the virus antigens from phosphate buffered saline, serum and peripheral blood. HIV-infected cells were eliminated in vitro, but not completely. This method will be useful in eliminating viral antigens and infected cells from clinical material such as blood and blood products. PMID- 2211958 TI - Competitive enzyme-immunoassays using native viral antigens to discriminate between HIV-1 and HIV-2 infections. AB - Human immunodeficiency virus (HIV) strains can be separated into two serotypes: HIV-1 and HIV-2. In the study reported herein, we developed and evaluated competitive enzyme-immunoassays (CEIA-1 for the detection of antibody to HIV-1, CEIA-2 for the detection of antibody to HIV-2) to discriminate serologically between HIV-1 and HIV-2 infections. In most of the cases, the serotyping of known reactive serum samples was done easily with the CEIAs, showing a similar specificity to the Western blot. Such competitive assays could represent alternative procedures for serotyping HIV infection and would limit the need for expensive Western blots, especially in economically poor countries. PMID- 2211959 TI - A microscale analytical batch chromatographic method for detecting soluble viral DNA-binding proteins in crude extracts. AB - We describe a micro-method for determining the presence in crude cellular extracts of soluble proteins which can bind to immobilized DNA, using the DNA binding protein of human adenovirus as an example. Batch chromatography of radiolabeled proteins is performed in microcentrifuge tubes containing 50 microliters packed volume of commercially available denatured calf thymus DNA cellulose. Eluted single-stranded DNA-binding proteins are then visualized by fluorography following gel electrophoresis. The batch procedure gives yields of adenovirus DNA-binding protein which are comparable to those obtained with a mini column of similar adsorbent volume. The scale of the procedure makes it convenient for simultaneously analyzing multiple samples. PMID- 2211960 TI - Lysophosphatidylethanolamine is the antigen to which apparent antibody to phosphatidylethanolamine binds. AB - Because binding of antiphospholipid antibody (aPL) to phosphatidylethanolamine (PE) is central to the definition of the antigenic epitope targeted by aPLs, we examined the binding of aPL-positive SLE sera to PE under various conditions. No serum bound to PE uncontaminated with lysophosphatidylethanolamine (1PE), but many aPL-positive sera bound to 1PE-contaminated PE and to 1PE coated onto an ELISA plate. Absorption studies indicated partial cross-reactivity between PE containing 1PE and cardiolipin. We conclude that clinical aPLs do not bind to PE. Prior reports to the contrary most likely represent binding of aPL to PE's degradation product, 1PE. PMID- 2211961 TI - Radiographic determination of prenatal basicranial ossification. AB - In a previous investigation on prenatal development of the human cranial base, the sequence in which the bones develop in the midsagittal region was elucidated. The purpose of the present study was to identify fetal ossification on horizontal plane roentgenograms of the occipital and sphenoid bones in the central part of the cranial base, and establish stages in bone appearance related to general fetal developmental parameters. This study is based upon roentgenograms of the cranial base of 145 human fetuses from the first half of the prenatal period. Two different maturation patterns of the sphenoid bone were observed. The first, most common pattern is characterized by a midsagittal centre of ossification and the second by bilateral centres of ossification in the corpus of the sphenoid bone. These bilateral centres might in some cases be connected by a slight bony bridge. It appears that these different maturation patterns are maintained throughout the period investigated. The material was divided into five well-defined developmental stages for both maturation patterns and general parameters of fetal development. Mapping different aspects of ossification in normal cranial development is necessary for understanding deviations of cranial maturation and growth. PMID- 2211962 TI - A craniometric study of the C. de Lange syndrome (CdLS). AB - After a short review of our method, we compared the results of the radiographs of 18 cases of CdLS to the results of our normal material. All of our normal statistical data was obtained from AP and lateral view radiographs at a distance of 1 m, in the prevailing conditions of everyday practice in a radiological department. We studied quantitative changes such as microcephaly and brachycephaly, and for the first time we introduced qualitative changes such as occipital rotation and the study of obliquity of the foramen magnum (line BAO). We found microcephaly in all our cases of CdLS and brachycephaly in only 72%. Furthermore, we found a lack of positive occipital rotation in all our cases of CdLS and the line BAO turned posteriorly with O higher than BA. The same conditions were observed on our normal material only in an early postnatal stage. PMID- 2211963 TI - Origin, formation, and prenatal maturation of the human cerebral cortex: an overview. PMID- 2211964 TI - Anencephaly: its spectrum and relationship to neural tube defects. AB - Anencephaly patients are of renewed interest because they are regarded as a potential source of organ donation. While there has been a longstanding scientific curiosity on this subject, studies have frequently included such cases as part of the larger spectrum of neural tube defects (NTDs). This paper will discuss some unusual features of anencephaly. Following a review of classification and pathogenesis, associated malformations, growth parameters (organ size and anthropometric measurements), and associations with other entities are discussed. Finally, the relationship of anencephaly to NTDs is presented. PMID- 2211965 TI - Microcephaly: general considerations and aids to nosology. AB - Microcephaly is defined as an occipito-frontal head circumference (OFC) 2 or more standard deviations below the mean for age and sex using the new Roche et al. [Pediatrics 1987;79:706-712] charts, and corrected for parental OFC by the method of Weaver and Christian [J Pediatr 1980;96:990-994]. "Relative" microcephaly, i.e., a small head on a small child, may be associated with a much better intellectual prognosis than absolute microcephaly, although the average IQ of children with absolute microcephaly ascertained in a normal school system is normal when compared with that of appropriate control children. "Primary" microcephaly means an abnormal OFC at birth (corrected for gestational age and length), and "secondary" microcephaly a normal birth OFC with later, acquired microcephaly due to deceleration of brain growth reflecting infection, trauma, intoxication, metabolic disease, the Rett syndrome, or a true CNS degenerative disease. Some cases of syndromal microcephaly may be associated with normal intelligence including some "primordial dwarfs," children with Dubowitz syndrome, FAS, mild SC-Roberts syndrome, and an occasional Brachmann-de Lange individual. The nosology of (syndromal) microcephaly is extraordinarily complex and requires the assistance of special library resources and information retrieval expertise. At a minimum, it requires McKusick's Catalog of Mendelian Inheritance in Man (MIM); however, we find that our work is greatly enhanced by recently developed electronic databases such as MIM-online (OMIM), POSSUM, SYNDROME, and MEDLINE, as well. Three groups of syndromal and non-syndromal microcephaly are discussed selectively in order to illustrate the marvels of pleiotropy in human development and its abnormalities and the difficulties encountered in splitting and lumping entities with overlapping manifestations. PMID- 2211966 TI - Primary neonatal hyperparathyroidism: a devastating neurodevelopmental disorder if left untreated. AB - We describe a 29-year-old male with untreated primary neonatal hyperparathyroidism. Hypotonia, poor feeding, failure to thrive, and developmental delay were noted in early infancy and in incidental serum calcium of 3.8 mmol/L was dismissed as a laboratory error. Childhood was characterized by profound muscle wasting and progressive spastic quadriparesis. Distinctive skeletal deformities, facial dysmorphism, and perichondral calcifications are now evident in adulthood. Elevated serum calcium (range: 2.7-3.3 mM; normal less than 2.7 mM), serum immunoreactive parathyroid hormone (range: 1,405-1,817 pg/mL; normal 50-140 pg/mL), and markedly decreased urinary calcium excretion (0.04 mumol/dL glomerular filtrate; normal greater than 25) suggested the diagnosis of primary neonatal hyperparathyroidism. This was supported by evidence of hypocalciuric hypercalcemia--the autosomal dominant carrier state--in both the parents. Our case illustrates the profound neurodevelopmental deficits arising from sustained hypercalcemia in infancy and childhood. Although this disorder is not lethal, it should be considered a neonatal emergency, since surgical parathyroidectomy can result in cure. PMID- 2211967 TI - Selected clinical research involving the central nervous system. AB - This paper updates three clinical research projects involving the central nervous system. Discussions of conditions with encephalocele include several associations: encephalocele/craniostenosis, transsphenoidal encephalocele/hypothalamic-pituitary dysfunction, encephalocele/oculo-auriculo vertebral spectrum, and encephalocele/frontonasal dysplasia. The relationship between oculo-auriculo-vetebral spectrum with encephalocele and frontonasal dysplasia with epibulbar dermoids and ear tags is also discussed and an explanation for encephalocele formation in the Apert syndrome is provided. Studies of the central nervous system in Apert syndrome indicate that distortion ventriculomegaly is common, but progressive hydrocephalus occurs infrequently. A recurrent pattern of abnormalities was discerned consisting of megalencephaly, gyral abnormalities, and defects of the corpus callosum and limbic structures. Five neuropathologic studies lend further support to this pattern of CNS anomalies in the Apert syndrome. In a study of holoprosencephaly, eight principles governing associated facial dysmorphism were derived. Each diagnostic category was shown to have its own frequency and range of holoprosencephalic faces. Some categories, such as del(13q), have narrow ranges; others, such as trisomy 13 syndrome, have broad ranges. However, no broad diagnostic range is known to include agnathia-holoprosencephaly and other severe forms of facial dysmorphism without agnathia. Absent maxillary incisors and a single maxillary central incisor are extremely common in holoprosencephaly with severe facial dysmorphism and may occur on occasion as a striking microform of holoprosencephaly, most commonly in the autosomal dominant form. PMID- 2211968 TI - Verbal and nonverbal communication of events in learning-disability subtypes. AB - This study compared a group of nondisabled children (ND) with groups of learning disabled children who were primarily impaired in reading and arithmetic skills (Reading-Arithmetic Disabled; RAD) and arithmetic but not reading (Arithmetic Disabled; AD) on a set of tasks involving comprehension and production of verbally and nonverbally presented events. Children viewed videotaped scenarios presented in verbal (narrative) and nonverbal (puppet actors) formats and were asked to describe or enact with puppets the events depicted in the stories. Rourke (1978, 1982) has shown that RAD children have problems with verbal skills, whereas AD children have problems with nonverbal skills. Consequently, it was hypothesized that children's performance in comprehending and reproducing stories would be related to the type of learning disability. Results showed that RAD children made more errors than AD children with verbal presentations and describe responses, whereas AD children made more errors than RAD children with nonverbal presentations and enact-responses. In addition, learning disabled children were more likely than controls to misinterpret affect and motivation depicted in the stories. These results show that learning disabled children have problems with social communication skills, but that the nature of these problems varies with the type of learning disability. PMID- 2211969 TI - Dichotic listening and complex partial seizures. AB - This study reports on 24 patients with multiple symptoms of untreated complex partial seizures (CPSz) who performed poorly at baseline assessment on a brief dichotic word listening task and subsequently improved following successful anticonvulsant therapy directed at treating seizure symptoms. These preliminary findings suggest that, in the absence of macroscopic structural lesions, dynamic electrophysiological dysfunction may interfere with the processing and transmission of simultaneously presented auditory information. PMID- 2211970 TI - Right and left orientation in children aged 5 to 13 years. AB - A 32-item test of right/left orientation was administered to 360 normal children, aged 5 to 13 years. The distribution of scores was tested to determine if parametric descriptive statistics were appropriate. As the distribution was multimodal, the test of normality was rejected. The three modes were consistent with a stage development theory, with the respective modes being consistent with (a) no understanding of right/left, (b) a personal or egocentric understanding of right/left, and (c) a generalization of right/left to external objects. Therefore, the data are presented in terms of the probability of obtaining a specific score at a given age. Scores were not found to be related to sex and were weakly, if at all, related to level of psychometric intelligence. PMID- 2211971 TI - Associative agnosias and the functions of the left hemisphere. AB - Associative agnosias are traditionally regarded as perceptual, and ideational apraxia as motor, deficits, but they can be understood as amnesias for generic knowledge, caused by bilateral or unilateral left-hemispheric cortical lesions. Current theories of hemispheric specialization explain these syndromes' mandatory link with left-hemispheric damage, and are validated by this link. This link reflects the multiple nature of generic, categorical representational systems, not all reducible to natural language, and the left hemisphere's principal role as their substrate, regardless of their dependence on language. The distinction between processing novel information, and processing based on well-established, routinized representations, captures a fundamental difference between the functions of the right and left hemispheres. The complementary link of apperceptive agnosias with right-and associative agnosias with left-hemisphere lesions is an expression of this general principle in the posterior cortex. Future studies of the neuroanatomy of agnosias in animals may offer insights into the evolutionary continuities of hemispheric specialization. PMID- 2211972 TI - The American Liner New York and Anna Thompson: an investigation of interference effects on the Wechsler Memory Scale. AB - The role of proactive interference in verbal memory was examined in 154 normal and brain-damaged subjects. Subjects were matched on age, sex, education, presence or absence of brain damage, and administered the Wechsler Memory Scale (WMS) Stories in standard order (A+B) or reverse order (B+A). Both normal and brain-damaged subjects recalled fewer details from Story B than Story A regardless of order of administration. We conclude that Story B from the WMS is inherently a more difficult passage to recall than Story A. The recall of fewer Story B items relative to Story A is expected and not due to proactive interference. PMID- 2211973 TI - Neuropsychological recovery in patients with moderate to severe head injury: 2 year follow-up. AB - Neuropsychological outcome and recovery of a group of 31 consecutive adult patients with moderate to severe head injuries were prospectively investigated over a 2-year period. A friend control group was used for comparison purposes. Based on the results we conclude: (1) there is marked impairment of a broad spectrum of neuropsychological functions at 1, 12, and 24 months postinjury; (2) coma length is significantly related to neuropsychological status at all three time periods, although the relationship is weaker at 12 and 24 months; (3) marked improvement in all functions occurs in the first year, while recovery in the second year appears more specific and may depend on the severity of the injury and type of function; (4) practice effects and variability over repeated measures cause difficulties in determining recovery and need to be addressed with larger samples. PMID- 2211975 TI - Predicting development of dementia in the elderly with the Selective Reminding Test. AB - The ability to predict the development of dementia through the detection of memory impairment in nondemented individuals was assessed with the Selective Reminding Test (SR), a popular test of verbal memory functioning in the elderly. The SR was administered to 385 nondemented volunteer subjects (mean age = 80.4 years) enrolled in a longitudinal study of risk factors in the development of dementia. Of these, 36 subjects ultimately became demented. SR scores obtained from 1 to 2 years prior to the diagnosis of dementia were compared with a set of previously established cutoff scores derived from a cognitively normal elderly sample. The results demonstrated that sum of recall and delayed recall were the SR measures best able to predict dementia with sensitivities of 47% and 44%, respectively. The predictive values were 37% and 40%, respectively, or better than two-and-one-half times the base rate. The contributions of both the SR Test and the Fuld Object-Memory Test (OM) were discussed in terms of the further understanding of the characteristics of the preclinical phase of dementia. PMID- 2211974 TI - Object-memory evaluation for prospective detection of dementia in normal functioning elderly: predictive and normative data. AB - In a prospective study of dementia in initially normal functioning elderly, a brief form of the Fuld Object-Memory Evaluation (OM) was administered to 474 cognitively normal community-residing volunteers aged 75-85 at baseline and annually thereafter. Seventy-two subjects later became demented. Memory test data from the last annual evaluation before cognitive change was noted were available for 56. Although the entire population recalled 7.28 (SD = 1.33) of the 10 objects on Trial 1 of the test at baseline, these 56 subjects recalled only 5.96 (SD = 1.85). When recall of 6 or fewer objects was used as a predictor, the OM test identified 32 of the 56 who subsequently became demented. Compared to an estimated base rate of 15% for dementia, the predictive value of a positive test (PV+) was 39%, and that of a negative test (PV-) was 89%. With a cutoff of 5 or fewer items recalled, the PV+ rose to 59% and the PV- was 94%. Although the OM test was only moderately sensitive to incipient dementia (.57), it was fairly specific (.84), and lowering the cutoff to 5 increased the specificity to .96. Memory testing would therefore seem to hold promise as a predictor of dementia in cognitively normal elderly. PMID- 2211976 TI - Dichotic listening, forced attention, and brain asymmetry in righthanded and lefthanded children. AB - Righthanded and lefthanded 7-year-old children (both boys and girls) were compared for dichotic listening performance under free report and forced attention conditions. Previous findings from our laboratory have shown that, while adults reverse the right ear advantage (REA) during the forced-left condition, children do not. Since the finding in children was unexpected, the first aim of the present study was to replicate our previous results. A second aim was to include lefthanded children with the hypothesis that they should more easily revert to a LEA, because of less homogeneous lateralization. The results essentially replicated our previous findings, during all three recall conditions. No sex differences were observed, and both handedness groups showed the same overall response pattern. PMID- 2211977 TI - Quantitative assessment of covariation between neuropsychological function and location of naturally occurring lesions in humans. AB - Studies of localization of brain function in humans depend on analysis of covariation between the location of naturally occurring lesions and measures of neuropsychological ability. Such an analysis presents two problems: how to represent numerically the infinite variety of lesion locations, sizes, and shapes; and how to assess covariation between the location measure and performance. We present a mathematical model of lesion location and its relationship with performance. To demonstrate its utility, the model is applied to a sample of 53 patients with naturally occurring brain lesions who were administered a standard battery of neuropsychological tests. Importance functions derived for the neuropsychological measures generally conform to expectations. Sensory and motor abilities were localized correctly within the contralateral hemispheres, and language functions were localized in the left frontal region. Lesion location accounts for substantially more variation in performance than does lesion volume, with location accounting for more than 50% for some left hemisphere functions. PMID- 2211978 TI - Memory impairment in multiple sclerosis. AB - We compared the performance of 50 multiple sclerosis (MS) patients and 35 normal controls on a variety of memory tasks to determine the nature and severity of memory deficits in the MS patients and the proportion of patients affected. We also determined the relationship between memory and other cognitive functions, demographic factors, disease characteristics, depression, and psychoactive medication. We found significant differences between patients and controls on almost all memory tests. Patterns of learning, effects of interference, and improvement with cuing were similar for both groups. Thirty percent of patients showed severe memory impairment, 30% were moderately impaired, and 40% were mildly or not impaired. Memory dysfunction was related to impairment of other cognitive functions, lower socioeconomic status, chronic progressive type of MS, and use of antianxiety medication, but not to severity of disability, duration of MS symptoms or depression. PMID- 2211979 TI - Heterogeneity in the cognitive profile of normal elderly. AB - An increasing number of studies point to the fact that distinct cognitive subgroups may be identified among subjects with dementia of the Alzheimer type (DAT). Although such heterogeneity could be the expression of neuropsychological, genetic, or epidemiological factors, the identification of neuropsychological subtypes in DAT could also reflect the existence of cognitive subgroups in a normal aged population. In the present study, the existence of neuropsychological subgroups was sought from among 81 volunteers aged between 55 and 84 years. Subjects were given a neuropsychological battery addressing various aspects of cognitive functioning. Results show that six subgroups could be identified among this population. Subgroups differ primarily in their overall degree of performance. Qualitative differences in cognitive performance are also present, mostly when subgroups which exhibit poor overall performance are considered. Consequently, the presence of such heterogeneity in normal elderly should be taken into account in any attempt to identify neuropsychologically based subgroups in early dementia of the Alzheimer type. PMID- 2211980 TI - Dysnomia in dementia and in stroke patients: different underlying cognitive deficits. AB - The performance of 11 Alzheimer's (DAT) and 8 anomic aphasic stroke patients is contrasted with that of 32 normal elderly subjects on both the Boston Naming Test (BNT) and the Controlled Oral Word Association Test (COW), a letter-category verbal-fluency test. While both tests require phonological processing, only the BNT requires semantic processing (object recognition). Both DAT and anomic aphasic stroke patients were significantly impaired on the BNT, with mean z scores (based on the performance of the normals) of -4.08 and -2.57, respectively; the DAT patients were significantly farther from normal than were the anomic aphasics. Their relative levels of impairment on the COW were reversed: The anomic aphasics' performance (z = 1.79) was worse than that of the DATs (z = -0.66). This pattern of performance on the two tests is consistent with the hypothesis that impaired word finding reflects impaired processing mainly of semantic information for the DAT subjects, mainly of lexical-phonological information for the anomic aphasic subjects. PMID- 2211981 TI - Effect of a hypoglycemic episode on neuropsychological functioning in diabetic children. AB - The present study investigated neuropsychological functioning in school-age children at various points in time surrounding a hypoglycemic episode using 13 tasks drawn from age-appropriate, standard neuropsychological tests. The results demonstrate the effects of a hypoglycemic episode on neuropsychological functioning even after detectable physical symptoms have subsided. Although we are unable to delineate clearly their temporal course, it appears that the impact of such episodes is transient. In general, the pattern exhibited by these children who have presumably recovered from their mild hypoglycemic episode involved reduced motor performance, attention, and memory. The observed prolonged recovery time of these functions presents important implications for the child in both school and social settings. PMID- 2211982 TI - Immunoreactive growth hormone-releasing hormone in rat leukocytes. AB - In the present study, we evaluated whether mononuclear leukocytes could synthesize and secrete growth hormone-releasing hormone (GHRH) in vitro. By using RNA slot-blot analysis, we detected maximum basal levels of specific GHRH mRNA in the cytoplasm of rat leukocytes after an 8 h in vitro incubation. Northern gel analysis demonstrated that the specific GHRH RNA was polyadenylated and had a molecular mass of approximately 0.8 kDa. Further studies using antibody affinity chromatography followed by size separation on high-performance liquid chromatography (HPLC) columns showed two peaks of immunoreactive (ir) material, a large molecular weight species, and a smaller molecular weight species at approximately 5 kDa. The smaller molecular weight irGHRH appeared to be de novo synthesized since it could be radiolabeled with tritiated amino acids. Both molecular species were detectable in enzyme-linked immunosorbent assay (ELISA) with specific antibodies made to the first 23 amino acids as well as specific antibody obtained commercially made to the entire molecule (1-43). Although the larger molecular weight form appeared to be the more predominant, only the lower molecular weight form could block the binding of 125I-hGHRH to pituitary cells. Most importantly, the lower molecular weight leukocyte-derived GHRH stimulated an increase in the level of GH RNA in the pituitary. We conclude that lymphocytes produce an irGHRH that is similar to hypothalamic GHRH in terms of bioactivity, antigenicity, and molecular weight. The findings demonstrate a potential regulatory loop between the immune and neuroendocrine tissues. PMID- 2211983 TI - Restraint stress-induced suppression of major histocompatibility complex class II expression by murine peritoneal macrophages. AB - The macrophage plays a central role in the development of immune responses. Macrophages take up and process antigen which is presented to antigen-responsive T lymphocytes in association with major histocompatibility complex class II (Ia) glycoproteins. We have investigated the effect of restraint stress on Ia expression by murine peritoneal macrophages. Stress resulted in a suppression of Ia expression which coincided with an increase in plasma corticosterone levels. In vitro experiments indicate that suppression of Ia expression can occur within 2 h after exposure to corticosterone. The suppression of this important aspect of macrophage function by stressors has important implications regarding the possible immunosuppressive effects of stress on the response of lymphocytes to antigens that depend on intact macrophage function. PMID- 2211984 TI - Influence of sex on susceptibility in the Theiler's murine encephalomyelitis virus model for multiple sclerosis. AB - Multiple sclerosis (MS) is a demyelinating disease in humans which affects females more frequently than males. Theiler's murine encephalomyelitis virus (TMEV) induces demyelination similar to human MS in susceptible strains of mice after intracerebral inoculation. In this paper we report that sex influences susceptibility to TMEV-induced demyelination in certain genotypes derived from C57L/J and SJL/J or SWR/J mice. This is the first report of an animal model for MS that shows an association between sex and susceptibility, and this information may facilitate the investigation of human MS. PMID- 2211985 TI - Expression of the CD6 T lymphocyte differentiation antigen in normal human brain. AB - Antigens shared by the immune and central nervous systems (CNS) have been described repeatedly. The present study reports the expression of the CD6 lymphocyte differentiation antigen in normal human brain evidenced by immunohistochemistry and Northern blot analysis. A panel of various anti-CD6 monoclonal antibodies (mabs) tested on serial cryostat sections identified CD6 positive cells randomly scattered in parenchyma of all examined brain areas. Northern blot analysis with a highly sensitive cRNA probe revealed a 3.1 kb CD6 specific mRNA in various brain regions, especially in basal ganglia and cortex cerebellum. Staining with mabs raised against different hematopoietic cell types, as well as hybridization with probes specific for the beta- and gamma-T cell receptor (TCR) chains support the notion that CD6 is expressed by original brain cells. The nature of the CD6-positive cell type and possible functions of shared antigens in immune and nervous systems are discussed. PMID- 2211986 TI - Attenuation of experimental autoimmune encephalomyelitis by Compound 48/80 in Lewis rats. AB - The appearance of increased levels of histamine in the central nervous system (CNS) concomitant with the development of clinically significant acute experimental autoimmune encephalomyelitis (EAE) in male Lewis rats suggests that CNS-associated mast cells may mediate acute EAE in Lewis rats. We now report that, compared to controls, rats with acute EAE exhibit fewer detectable mast cells in their dura mater and velum interpositum. In addition, intracisternal, but not intraperitoneal administration of Compound 48/80 just prior to the appearance of clinical signs of acute or recurrent EAE in male and female rats, respectively, significantly attenuates the clinical severity of both forms of EAE. These results further support the hypothesis that CNS-associated, but not peripheral mast cells are mediators or modulators of acute and recurrent EAE in Lewis rats. PMID- 2211987 TI - In vitro studies on the characterization of cellular proliferation following neuronal injury in the adult rat brain. AB - While brain injury elicits local cellular proliferation, it is not known whether cells not originating in brain substantially participate in the response. We assessed the time course and phenotype of dividing cells following neuronal damage initiated by microinjection of the neurotoxin ibotenic acid into one caudate nucleus (CN) in adult rat. Proliferation was determined in an in vitro assay measuring incorporation of [3H]thymidine into cellular DNA in cultures of lesioned and uninjected CN. Cellular phenotypes were determined immunocytochemically. Our results show that the proliferative response to brain injury has a rapid onset, peaks within 2 weeks and persists. The majority of proliferating cells that respond to selective neuronal injury are not intrinsic to the central nervous system, but rather are of hematic origin, involving monocytes, macrophages and T-helper lymphocytes. PMID- 2211988 TI - Evidence for autoimmune antibodies directed against embryonic neural cell adhesion molecules (N-CAM) in patients with group B meningitis. AB - Human brain tissue shares alpha 2-8 linked polymers of neuraminic acid with the carbohydrates expressed on the capsule of group B Neisseria meningitidis bacteria (Finne et al. (1983) Lancet ii, 355-357; Finne (1985) Trends Biochem. Sci. 10, 129-132; Rougon et al. (1986) J. Cell. Biol. 103, 2429-2437). We report that sera from patients suffering from group B meningitis exhibited IgM antibodies directed against the embryonic, but not the adult, form of neural cell adhesion molecules (N-CAM). These sera also stained live ATt20 cells as well as neuron membranes in mouse embryonic brain cultures. We have demonstrated that such antibodies, directed against carbohydrate moieties of bacterial capsula, were able to lyse cells expressing embryonic N-CAM in a complement-dependent cytotoxic assay. These data infer (1) that humans are able to develop anti-MenB humoral responses, (2) that such responses could initiate autoimmune disorders or be potentially detrimental by interfering with processes mediated by N-CAM interactions, (3) that the development of a vaccine against group B meningitidis should be considered with caution. PMID- 2211989 TI - On the mechanism of high-dose intravenous immunoglobulin treatment of patients with chronic inflammatory demyelinating polyneuropathy. AB - A proportion of patients with a chronic inflammatory demyelinating polyneuropathy (CIDP) improves after polyvalent intravenous immunoglobulin (IVIg) treatment. When anti-neuroblastoma cell line (NBL) antibodies are present, they decrease or disappear after IVIg treatment. Purified IgM anti-NBL antibodies from a CIDP patient were inhibited by F(ab')2 of IVIg and by F(ab')2 of a patient recovered from Guillain-Barre syndrome (GBS). Inhibition of anti-NBL antibodies was also found among sera from normal individuals. This suggests that the self-limiting character of GBS and the therapeutic effect of IVIg in CIDP are dependent on suppression of auto-antibodies. This suppression may be mediated by anti idiotypes present in recovered GBS patients and in the normal donor population contributing to IVIg. PMID- 2211991 TI - Electroclinical syndromes in infancy. PMID- 2211990 TI - Adult thymus expresses an embryonic nicotinic acetylcholine receptor-like protein. AB - The subunit composition of acetylcholine receptor-like protein(s) (AChR-LP) expressed by normal thymus was investigated. In skeletal muscle, the AChR exists in two forms, an embryonic form which contains the gamma-subunit and an adult form where the gamma-subunit is substituted by a different, homologous subunit called epsilon. Antibodies against unique sequence segments of the embryonic gamma-subunit and of the adult epsilon-subunit of bovine muscle AChR, in addition to antibodies specific for the alpha-, beta-, and delta-subunits of bovine muscle AChR, were used to probe immunoblots of AChR-LP(s) from bovine thymus. Subunits of approximate Mr 41 kDa, 48-54 kDa, 57 kDa and 67-72 kDa were recognized by anti alpha, anti-beta, anti-gamma and anti-delta antibodies respectively. Anti-epsilon antibodies did not recognize any protein band from bovine thymus. AChR-LP similar or identical to the embryonic muscle AChR is therefore expressed in normal thymus. PMID- 2211992 TI - Electrophysiological brain maturation in premature infants: an historical perspective. AB - The EEG is an excellent method for measuring brain maturation in premature neonates. Characteristic patterns typify each conceptional age (CA) (age in weeks from conception) and allow the experienced reader to predict within +/- 2 weeks the infant's CA. This paper reviews from an historical perspective (beginning with Berger) the dramatic changes the EEG undergoes from early premature birth (CA, 26 weeks) to term (CA, 40 weeks). The important features of normal EEG development are discussed as well as the clinical significance of an apparent arrest or delay of the normal developmental process, the so-called "dysmature" pattern. It is proposed that close attention to the stage of brain maturation in normal and abnormal EEGs might allow more accurate timing of the brain insult in infants with neurological sequelae. PMID- 2211994 TI - Benign neonatal seizures. AB - Benign neonatal seizures is a rare but increasingly recognized syndrome characterized by seizures in the neonatal or infantile period. Two forms are recognized: familial and nonfamilial. In both instances, the seizures may be quite severe, and status epilepticus is common. The nonfamilial form is characterized by idiopathic, self-limited seizures occurring in previously normal neonates. The seizures most commonly occur at day 5 and have been called "fifth day fits" by some authors. Familial seizures most frequently have their onset during the first week of life, but onset may occur as late as early infancy. These seizures may recur for several months before resolving. No cause is found for the seizures, and the patient appears healthy during the interictal period. The family history reveals benign neonatal seizures in other family members. Although the prognosis is favorable in both syndromes, seizures may occasionally occur later in life in the familial form. The familial form of benign neonatal seizures is autosomal dominant, and the gene has been localized to chromosome 20. PMID- 2211993 TI - What is a neonatal seizure? Problems in definition and quantification for investigative and clinical purposes. AB - Despite the clinical and basic scientific importance of neonatal seizures, a standard operational definition of them is lacking. Virtually all quantitative studies of phenomenology, prevalence, treatment efficacy, and prognosis have been undermined by inadequate or inconsistent criteria for the object of investigation. This is not so much a fault of the studies, however, as a consequence of the very nature of neonatal seizures themselves, which seem to defy universally applicable definitions and criteria for quantification. The main obstacles to formulating such definitions are reviewed, and directions for further research are suggested. PMID- 2211995 TI - Benign infantile epilepsy with complex partial seizures. AB - Benign infantile epilepsy with complex partial seizures is characterized by a high incidence of family history of benign childhood convulsions, normal development prior to onset, infantile onset, no underlying disorders, no neurological abnormalities, normal interictal EEGs, good response to treatment, and complete remission with normal developmental outcome. Seizures often occur in clusters, consisting of motion arrest, decreased responsiveness, staring or blank eyes mostly with simple automatisms, and mild convulsive movements associated with focal paroxysmal discharges, most frequently in the temporal area. PMID- 2211996 TI - Computer analyses of EEG-sleep in the neonate: methodological considerations. AB - Neonatal EEG interpretation can aid in the estimation of central nervous system maturation, as well as provide diagnostic and prognostic information of the high risk infant. However, one cannot easily visualize the complex interrelationships coupling EEG and polysomnographic components of the EEG-sleep rhythm. This is particularly relevant for the preterm neonate, in whom a rudimentary sleep cycle has not yet been clearly delineated. Computer analysis can augment the information derived from the visual interpretation of scalp-generated EEG activity. Automated techniques for EEG-sleep analysis have only recently been applied to a neonatal population. Such studies have been limited to full-term rather than preterm infants and rely on conventional methods that assume stationarity of neurophysiologic signals. We describe a computer system that simultaneously compares behavioral and electrographic components of EEG-sleep in a manner that preserves the integrity of the signals over time, while investigating the time- and frequency-dependent relationships among signals. Strategies for on-line and off-line editing, data storage, and off-line signal processing are described. Computational algorithms regarding analyses of EEG power, motility, and cardiorespiratory data are being used to study the ontogeny of EEG-sleep in asymptomatic preterm and full-term neonates. Computer strategies are based on both principles of stationarity and nonstationarity of physiologic signals and are applied depending on the temporal resolution required for specific signal processing needs. PMID- 2211997 TI - Neurophysiologic monitoring devices for infants and children. PMID- 2211998 TI - Structure and function of the T cell antigen receptor. PMID- 2211999 TI - Hyponatremia in rats induces downregulation of vasopressin synthesis. AB - Hyponatremia due to inappropriate secretion of vasopressin is a common disorder in human pathophysiology, but vasopressin synthesis during hypoosmolality has not been investigated. We used a new method to quantitate synthesis of vasopressin in rats after 3, 7, and 14 d of hyponatremia induced by administering dDAVP (a vasopressin agonist) and a liquid diet. Vasopressin synthesis was completely turned off by 7 d. Vasopressin mRNA levels in the hypothalamus paralleled the reduction in synthesis and were reduced to levels of only 10-15% of the content in control rats. When hyponatremia was corrected by withdrawal of dDAVP, vasopressin mRNA slowly returned to normal over 7 d. The observation that vasopressin synthesis can be so completely turned off leads to several conclusions: under normal physiological conditions the neurohypophysis is chronically upregulated; there must be an osmotic threshold for initiation of vasopressin synthesis (and release); the large store of hormone in the posterior pituitary is essential for vasopressin to be available during times of decreased synthesis; and, finally, some nonosmolar stimulus for synthesis must be present during clinical disorders when vasopressin is secreted (and synthesized) despite hypoosmolality. PMID- 2212000 TI - Fibronectin fragments containing the RGDS cell-binding domain mediate monocyte migration into the rabbit lung. A potential mechanism for C5 fragment-induced monocyte lung accumulation. AB - Many inflammatory processes are characterized by an early phase of neutrophil migration and a later phase of monocyte migration into the inflammatory site. Mechanisms that govern the transition between phases are the subject of these investigations. Acute lung inflammation induced by C5 fragments in the rabbit leads to an initial neutrophil influx and plasma leakage into the alveolar space, followed by monocyte influx that we have previously shown to be dependent on prior emigration of neutrophils. Neutrophil enzymes are known to cleave intact fibronectin into fragments that are monocyte chemotaxins in vitro. Accordingly, generation of appropriate fibronectin fragments in situ by proteolytic enzymes from infiltrating neutrophils might represent a potential mechanism for attraction of monocytes into the lung. The studies reported herein demonstrate that a 120-kD fragment of fibronectin containing the RGDS fibroblast cell-binding domain induced monocyte migration into the rabbit lung in vivo. Intact fibronectin was inactive. A significant proportion of the monocyte migration was neutrophil independent. Intact fibronectin was present in bronchoalveolar lavage fluid from C5 fragment-treated animals rendered neutropenic, but absent in lavage from normal C5 fragment-treated animals. Fibronectin fragments were present in bronchoalveolar lavage fluid from both C5 fragment-treated and control rabbits. In addition, the amount of fibronectin was significantly increased in lavage of C5 fragment-treated normal but not neutropenic animals. Monoclonal antibodies directed against an epitope of fibronectin containing the RGDS cell-binding domain significantly inhibited the C5 fragment-induced monocyte migration, but not neutrophil migration. These studies suggest that chemotactic fibronectin fragments may in part be responsible for the recruitment of monocytes into areas of acute lung inflammation. PMID- 2212001 TI - Mutation of the signal peptide-encoding region of the preproparathyroid hormone gene in familial isolated hypoparathyroidism. AB - Preproparathyroid hormone (preproPTH) gene mutation has been proposed as a cause of familial isolated hypoparathyroidism (FIH). We cloned the preproPTH alleles of a patient with autosomal dominant FIH and sequenced the coding regions, 5' flanking regions, and splice junctions. The putatively abnormal (based on previous linkage studies) allele differed from the other allele's normal sequence at only one nucleotide. This T to C point mutation changes the codon for position 18 of the 31 amino acid prepro sequence from cysteine to arginine, disrupting the hydrophobic core of the signal sequence. Because the hydrophobic core is required by secreted proteins for efficient translocation across the endoplasmic reticulum, the mutant protein is likely to be inefficiently processed. Indeed, in vitro studies demonstrated dramatically impaired processing of the mutant preproPTH to proPTH. In summary, we observed a point mutation in the signal peptide-encoding region of a preproPTH gene in one FIH kindred and demonstrated a functional defect caused by the mutation. Mutation of the signal sequence constitutes a novel pathophysiologic mechanism in man, and further study may yield important insights both into this form of hormone deficiency and into the role of signal sequences in human physiology. PMID- 2212002 TI - Essential fatty acid deficiency ameliorates acute renal dysfunction in the rat after the administration of the aminonucleoside of puromycin. AB - The administration of the aminonucleoside of puromycin (PAN) to rats causes the nephrotic syndrome that is associated with an acute decline in renal function, and an interstitial infiltrate. We examined whether essential fatty acid deficiency (EFAD), which inhibits macrophage infiltration in glomerulonephritis, affects PAN-induced renal dysfunction. Both control and EFAD rats developed proteinuria that resolved over 28 d. After PAN administration, there was a prominent infiltration of macrophages in rats fed a normal diet. The infiltrate was prevented by the EFAD diet. The absence of a macrophage interstitial infiltrate was associated with a significantly higher Cin in the EFAD rats than in controls at 7 d (5.21 +/- 1.19 versus 0.39 +/- 0.08, P less than 0.002 ml/min/kg BW). In addition, CPAH fell to less than 10 ml/min/kg BW by day 7 in controls, but remained the same as normal in the EFAD. After administration of PAN to control rats, there was no increase in urinary thromboxane excretion or an increase in glomerular thromboxane production. Furthermore, the effect of EFAD could not be mimicked by the administration of a thromboxane synthase inhibitor. Irradiation-induced leukopenia in rats on a normal diet markedly improved glomerular filtration and renal blood flow in acutely nephrotic rats. EFAD prevents the interstitial cellular infiltrate and the renal ischemia associated with experimental nephrosis. The recruitment of mononuclear cells into the kidney following PAN directly contributes to the decline in renal function. PMID- 2212004 TI - Deletion of Alu sequences in the fifth c-sis intron in individuals with meningiomas. AB - An abnormality in the c-sis protooncogene was identified in leukocyte DNA from members of a family predisposed to the development of meningioma, and was found to be associated with the development of the tumor in those individuals. Molecular analysis of this abnormality demonstrated a deletion within the fifth intron of the c-sis gene. The normal c-sis gene has an Alu sequence in this region which includes two perfect 130 nucleotide repeated sequences separated by 5 bp. The deleted c-sis allele is missing precisely one copy of the 130 bp repeat and the intervening 5 bp. An identical deletion was also found in DNA from 1 of 13 sporadic meningiomas. PMID- 2212005 TI - Molecular basis of hereditary C3 deficiency. AB - Hereditary deficiency of complement component C3 in a 10-yr-old boy was studied. C3 could not be detected by RIA of serum from the patient. Segregation of C3 S and C3 F allotypes within the family confirmed the presence of a null gene for C3, for which the patient was homozygous. 30 exons have been characterized, spanning the entire beta chain of C3 and the alpha chain as far as the C3d region. Sequence analysis of the exons derived from the C3 null gene showed no abnormalities in the coding sequences. A GT-AT mutation at the 5' donor splice site of the intervening sequence 18 was found in the C3 null gene. Exons 17-21 were amplified by the polymerase chain reaction (PCR) from first-strand cDNA synthesized from mRNA obtained from peripheral blood monocytes stimulated with LPS. This revealed a 61-bp deletion in exon 18, resulting from splicing of a cryptic 5' donor splice site in exon 18 with the normal 3' splice site in exon 19. This deletion leads to a disturbance of the reading frame of the mRNA with a stop codon 17 bp downstream from the abnormal splice in exon 18. His parents had both the normal and abnormal C3 mRNA and were shown to be heterozygous for this mutation by sequence analysis of genomic DNA amplified by PCR. Similar splice mutants have previously been reported in the beta-globin, phenylalanine hydroxylase, and porphobilinogen deaminase genes. This mutation is sufficient to cause the deficiency of C3 in the patient. PMID- 2212003 TI - Activation pathways of synovial T lymphocytes. Expression and function of the UM4D4/CDw60 antigen. AB - Accumulating evidence implicates a central role for synovial T cells in the pathogenesis of rheumatoid arthritis, but the activation pathways that drive proliferation and effector function of these cells are not known. We have recently generated a novel monoclonal antibody against a rheumatoid synovial T cell line that recognizes an antigen termed UM4D4 (CDw60). This antigen is expressed on a minority of peripheral blood T cells, and represents the surface component of a distinct pathway of human T cell activation. The current studies were performed to examine the expression and function of UM4D4 on T cells obtained from synovial fluid and synovial membranes of patients with rheumatoid arthritis and other forms of inflammatory joint disease. The UM4D4 antigen is expressed at high surface density on about three-fourths of synovial fluid T cells and on a small subset of synovial fluid natural killer cells; in synovial tissue it is present on more than 90% of T cells in lymphoid aggregates, and on approximately 50% of T cells in stromal infiltrates In addition, UM4D4 is expressed in synovial tissue on a previously undescribed population of HLA-DR/DP negative non-T cells with a dendritic morphology. Anti-UM4D4 was co-mitogenic for both RA and non-RA synovial fluid mononuclear cells, and induced IL-2 receptor expression. The UM4D4/CDw60 antigen may represent a functional activation pathway for synovial compartment T cells, which could play an important role in the pathogenesis of inflammatory arthritis. PMID- 2212006 TI - Apical membrane limits urea permeation across the rat inner medullary collecting duct. AB - Urea diffuses across the terminal inner medullary collecting duct (IMCD) via a facilitated transport pathway. To examine the mechanism of transcellular urea transport, membrane-apparent urea (Purea) and osmotic water (Pf) permeabilities of IMCD cells were measured by quantitative light microscopy in isolated IMCD-2 tubules perfused in the absence of vasopressin. Basolateral membrane Pf, determined by addition of raffinose to the bath, was 69 microns/s. Basolateral membrane Purea, determined by substituting urea for raffinose without change in osmolality, was 14 X 10(-5) cm/s. Bath phloretin inhibited basolateral Purea by 85% without a significant effect on Pf. The basolateral reflection coefficient for urea, determined by addition of urea in the presence of phloretin, was 1.0. These results indicate that urea crosses the basolateral membrane by diffusion, and not by solvent drag. In perfused tubules, the rate of cell swelling following substitution of urea for mannitol was significantly greater with bath than lumen changes. After correcting for membrane surface area, the basolateral membrane was twofold more permeable than the apical membrane. CONCLUSIONS: (a) in the absence of vasopressin, urea permeation across the IMCD cell is limited by the apical membrane; (b) the basolateral membrane contains a phloretin-sensitive urea transporter; (c) transepithelial urea transport occurs by movement of urea through the IMCD cell. PMID- 2212007 TI - Induction of renal growth and injury in the intact rat kidney by dietary deficiency of antioxidants. AB - We report induction of renal growth and injury in the intact rat kidney using a diet deficient in vitamin E and selenium. This diet was imposed in 3-wk-old male weanling rats, and after 9 wk, enhancement of growth, characterized by increased wet weight, dry weight, protein content, and DNA content appeared. Morphometric analyses revealed increased kidney volume, tubular epithelial volume, and mean glomerular volume. There were no differences in nephron number. The animals on the deficient diet displayed increased urinary protein excretion at 9 wk. Renal injury was also characterized by an interstitial cellular infiltrate and diminutions in glomerular filtration rate. Enhanced growth and injury were antedated by increased renal ammoniagenesis. The deficient diet did not induce metabolic acidosis, potassium depletion, glucose intolerance, or elevated plasma amino acid concentration. Enhancement of renal growth and ammoniagenesis by the deficient diet was not suppressible by chronic alkali therapy. Stimulation of renal growth could not be ascribed to increased intrarenal iron, induction of ornithine decarboxylase, or alterations in glomerular hemodynamics. Stimulation of renal ammoniagenesis by dietary deficiency of antioxidants is a novel finding, as is induction of growth and injury. We suggest that increased renal ammoniagenesis contributes to induction of renal growth and injury. PMID- 2212008 TI - Autoantibodies to the HLA-B27 sequence cross-react with the hypothetical peptide from the arthritis-associated Shigella plasmid. AB - We previously reported elevated serum antibody levels to a peptide representing the HLA-B27 polymorphic region (B27 peptide) in HLA-B27(+) ankylosing spondylitis (AS) patients. A plasmid (pHS-2) isolated from arthritogenic Shigella flexneri strains had been shown to encode an amino acid sequence homologous to HLA-B27. Rabbit antibody to this sequence (pHS-2 peptide) strongly cross-reacted with B27 peptide and, to a much lesser extent, with Klebsiella nitrogenase peptide. Serum antibody levels to pHS-2 peptide were studied in 160 spondylarthropathy patients. 12 of 115 (10.4%) AS patients, 2 of 45 (4.4%) patients with Reiter's syndrome or reactive arthritis as well as 6 of 147 (4.1%) normal controls were shown to have elevated anti-pHS-2 peptide antibodies. Antibody levels to B27 and pHS-2 peptides were significantly correlated in 134 HLA-B27(+) patients (r = 0.333, P less than 0.001). 13 of 15 affinity-purified anti-B27 peptide antibodies from patients strongly cross-reacted with pHS-2 peptide, whereas only 3 weakly cross-reacted to nitrogenase peptide. Leucine appeared to be a critical residue for this cross reaction. AS patients' anti-B27 peptide antibodies reacted with HLA-B27 transfected L cells. These results may suggest that pHS-2 peptide more efficiently "mimics" B27 peptide than does nitrogenase peptide. Involvement of pHS-2 in pathogenesis of spondylarthropathy through molecular mimicry mechanisms requires further study. PMID- 2212009 TI - Polyclonal B cell activation in lupus-prone mice precedes and predicts the development of autoimmune disease. AB - Polyclonal B cell activation is an early feature of autoimmune disease in humans and mice with systemic lupus erythematosus. The contribution of polyclonal activation to the progression of autoimmunity is unclear, however, since it precedes the development of end-organ damage by months or years. To examine this issue, 109 autoimmune-prone (NZB X NZW)F1 X NZB backcross mice were hemi splenectomized at 10 wk and the number and antigenic specificity of their Ig secreting B cells quantitated by ELISA spot assay. Of the 61 mice that had polyclonally increased numbers of Ig-secreting cells/spleen, 31 died by 6 mo. In contrast, 0/48 backcross mice with normal numbers of Ig-secreting B cells at 10 wk died over the same period (P less than 0.001). Polyclonally activated mice also developed proteinuria earlier and more frequently than littermates with normal numbers of Ig-secreting cells (P less than 0.001). As adults, backcross mice with proteinuria expressed repertoires skewed towards the production of anti DNA antibodies. At 10 wk these same mice expressed repertoires marked by polyclonal activation rather than preferential anti-DNA production. These findings indicate that autoimmune disease in SLE is accompanied by the autoantigen-driven production of autoantibodies but is preceded and predicted by polyclonal B cell activation. PMID- 2212011 TI - Role of lung fluid volume in growth and maturation of the fetal sheep lung. AB - We studied the effects of alterations in lung fluid volume on growth and maturation of the fetal lung. In a chronic fetal sheep preparation, right fetal lung volume was decreased by drainage of lung fluid while the volume of the left lung was expanded by mainstem bronchus ligation leading to lung fluid retention. After an experimental period of 25 d (from 105 to 129 d of gestation, term = 145 d), the right (deflated) lung was significantly hypoplastic and contained less DNA than the controls; 175.15 +/- 55.18 vs. 346.77 +/- 61.97 mg, respectively; P less than 0.001. In contrast, the left (expanded) lung was significantly hyperplastic and contained more DNA than the controls; 390.74 +/- 103.53 vs. 238.85 +/- 33.32 mg, respectively; P = 0.001. Biochemical indices of lung maturation, including total phospholipids, phosphatidylcholine, and disaturated phosphatidylcholine content expressed per unit of tissue DNA, were no different when comparing the hypoplastic, hyperplastic, and control lungs. These findings demonstrate that fetal lung cell multiplication is influenced by local distension with lung fluid, while the biochemical maturation of fetal lung surfactant is under systemic control. PMID- 2212010 TI - Expression of ras oncogenes in cultured human cells alters the transcriptional and posttranscriptional regulation of cytokine genes. AB - Autonomous production of cytokines such as the hematopoietic colony-stimulating factors (CSFs), IL-1, or IL-6 has been demonstrated in numerous human and murine neoplasms, and may be involved in the pathogenesis of several paraneoplastic syndromes such as leukocytosis, fever, and hypercalcemia. Because of the high frequency with which mutations in ras protooncogenes have been detected in human tumors, as well as evidence linking ras gene products to activation of certain cellular functions, we investigated whether ras mutations might influence the regulation of cytokine genes. Normal human fibroblasts transfected with a mutant val12 H-ras oncogene expressed increased levels of mRNA transcripts encoding granulocyte-CSF (G-CSF), granulocyte-macrophage-CSF (GM-CSF), and IL-1 beta compared with controls. Human mesothelioma cells transfected with a mutant asp12 N-ras oncogene exhibited similar alterations in cytokine gene expression. Estimates of transcriptional activity by nuclear run-on analysis revealed a selective increase in transcription only for the IL-1 gene. Analysis of mRNA half life demonstrated a marked increase in the stability of numerous cytokine transcripts, including G-CSF, GM-CSF, IL-1, and IL-6. The addition of anti-IL-1 neutralizing antibody to cultures of cells expressing ras mutants did not block the expression of any of the cytokines examined, suggesting that the baseline expression of GM-CSF, G-CSF, and IL-6 was not a secondary event due to the increased transcription of IL-1. These results indicate that mutations in ras genes may alter expression of several cytokine genes through both transcriptional and posttranscriptional mechanisms. PMID- 2212012 TI - Role of ventriculovascular coupling in cardiac response to increased contractility in closed-chest dogs. AB - While both dobutamine and pacing tachycardia augment left ventricular (LV) contractility, whether overall cardiovascular response to these stimuli is comparable is not known. To address this question we studied seven dogs previously instrumented with three LV diameter gauges and LV pressure manometers. After ganglionic blockade and sedation, caval occlusions were performed at heart rates of 120, 160, and 200 bpm before (C), and 160 and 200 bpm after administration of 10 micrograms/kg per min dobutamine, i.v. (D). The effective arterial elastance (Ea) went up from 14.2 +/- 4.5 mmHg/ml at C120 to 19.6 +/- 8.8 (P less than 0.025 vs C120) and 24.2 +/- 10.4 (P less than 0.001 vs C120) mmHg/ml at C160 and C200. Ees, the slope of the end-systolic pressure-volume relation, increased with pacing from 9.7 +/- 4.6 to 11.7 +/- 4.3 (P less than 0.02), and 13.2 +/- 5.7 (P less than 0.02) mmHg/ml at 160 and 200 bpm. With dobutamine infusion Ea went down, and Ees was further increased to 37.0 +/- 20.9 mmHg/ml at 160 bpm (P less than 0.002 vs C160), and 53.0 +/- 22.6 mmHg/ml at 200 bpm (P less than 0.002 vs C200). Comparison of stroke work and pressure-volume area from single beats with matched LV end-diastolic volumes showed that these were both increased by dobutamine, but not by pacing tachycardia. While increased heart rate after dobutamine markedly increased contractility, Ea was not changed, and neither stroke work nor pressure-volume was further increased. Thus, how well an increase in contractility is transmitted to the periphery is determined in part by arterial behavior. Assessment of both the arterial system and cardiac contractility is necessary to fully evaluate the overall impact of an inotropic stimulus. PMID- 2212014 TI - Cell surface expression of the 70-kD component of Ku, a DNA-binding nuclear autoantigen. AB - The Ku complex, a heterodimer of 86- and 70-kD proteins, is a nuclear DNA-binding autoantigen. However, hydrophobicity analysis of the deduced amino acid sequence of the 70-kD protein had strongly suggested that this might also be a membrane protein. In the present study, using antibodies to synthetic peptides and a polyclonal antiserum to the purified protein, we show that the 70-kD protein of the Ku complex is present in isolated plasma membranes of human cells. By indirect immunofluorescence microscopy and fluorescein-activated cell sorting, we demonstrate that this autoantigen is exposed on the cell surface. In addition, we have identified several domains of the protein that are exposed. Our study provides one of the first demonstrations of a eukaryotic, nuclear DNA-binding protein that is also on the cell membrane. Moreover, our results might help explain how autoantibodies to the Ku autoantigen could target cells for an autoimmune attack. PMID- 2212013 TI - Myocardial localization and isoforms of neural cell adhesion molecule (N-CAM) in the developing and transplanted human heart. AB - Neural cell adhesion molecule (N-CAM) has been implicated in cellular interactions involved in cardiac morphogenesis and innervation. Immunohistochemical techniques and Western blot analysis were used to determine the localization and isoforms of N-CAM in the developing and extrinsically denervated human heart. Myocardial and conducting cells in the fetal heart (7-24 wk gestation) exhibited sarcolemmal immunoreactivity, the major desialo N-CAM isoforms being 150, 145, 120, 115, and 110 kD. N-CAM expression appeared to be downregulated in the myocardium during adult life, with relatively little sarcolemmal immunoreactivity being detected in normal donor tissues. In contrast to the temporal changes observed in the myocardium, both the developing and mature cardiac innervation displayed N-CAM immunofluorescence staining, localized to neuronal cell bodies, nerve fascicles and fibres. Extrinsically denervated cardiac allografts, obtained 2 d to 91 mo after transplantation, showed extensive sarcolemmal and intercalated disc immunostaining and expression of 125-, 120-, and 115-kD isoforms. Tissues from explanted recipient hearts and atrial appendage samples obtained during coronary bypass graft operations were also examined and displayed varying amounts of N-CAM immunoreactivity. We conclude that the expression of N-CAM immunoreactivity and isoforms in the human heart is developmentally regulated and may be modulated by factors such as cardiac innervation and myocardial hypertrophy. PMID- 2212015 TI - Chylomicron remnant clearance from the plasma is normal in familial hypercholesterolemic homozygotes with defined receptor defects. AB - The retinyl palmitate fat tolerance test was used to measure chylomicron remnant clearance in 10 normal subjects (apolipoprotein E [apo E] isotypes 3 or 4 only), 6 normolipidemic apo E2/2 homozygotes and 5 familial hypercholesterolemic homozygotes. Skin fibroblasts with fully upregulated LDL receptors from the latter subjects degraded rabbit 125I-beta VLDL in vitro at rates ranging from less than 10-48% of normal. Experiments in vivo revealed no significant differences between the normal and homozygous familial hypercholesterolemic (FHH) subjects in chylomicron remnant clearance assessed on the basis of "areas under the curves" for retinyl palmitate levels present in post-prandial serum, chylomicron remnants (Sf. less than 1,000), or chylomicrons (Sf. greater than 1,000). Remnant clearance was greatly decreased at all times in the apo E2/2 homozygotes, indicative of an important degree of flux control exerted by a receptor-mediated step involving apo E as ligand. The absence of any excess remnant accumulation in FHH subjects with varying "impairment" of LDL receptor mediated degradation of apo E-containing lipoproteins, permits the conclusion that chylomicron remnants are initially cleared from the plasma by apo E recognizing receptors which are genetically distinct from LDL receptors. PMID- 2212016 TI - Regulation of parathyroid hormone gene expression by hypocalcemia, hypercalcemia, and vitamin D in the rat. AB - In vivo in the rat 1,25(OH)2D3 decreases and a low calcium increases PTH mRNA levels. We now report the effect of 3 and 8 wk of changes in dietary vitamin D and calcium on PTH mRNA levels. PTH mRNA levels were increased by 3 wk of calcium deficiency (five times), a vitamin D-deficient diet (two times), and combined deficiency (10 times), but not changed by high calcium. Vitamin D-deficient-diet rats' PTH mRNA did not decrease after a single large dose of 1,25(OH)2D3, but did decrease partially after repeated daily doses of 1,25(OH)2D3. Rats after a vitamin D-, calcium-deficient (-D-Ca) diet did not respond to changes in serum calcium at 1 h. Flow cytometry of isolated cells from parathyroid-thyroid tissue separated the smaller parathyroid from the larger thyroid cells and allowed an analysis of parathyroid cell number. In normal vitamin D/normal calcium (NDNCa) rats the parathyroid cells were 24.7 +/- 3.4% (n = 6) of the total cell number, whereas in -D-Ca rats they were 41.8 +/- 6.6% (n = 6) (P less than 0.05). That is, -D-Ca rats had 1.7 times the number of cells, whereas they had 10 times the amount of PTH mRNA, indicating the major contribution (6 times) of increased PTH gene expression per cell. Moreover, a calcium-deficient, more so than a vitamin D deficient diet, amplifies the expression of the PTH gene, and vitamin D is necessary for an intact response of PTH mRNA to 1,25(OH)2D3 or calcium. PMID- 2212017 TI - Endogenous angiotensin concentrations in specific intrarenal fluid compartments of the rat. AB - To examine angiotensin (ANG) concentrations in fluid compartments near known intrarenal ANG receptors, we measured ANG concentrations in glomerular filtrate (GF), star vessel plasma (SVP), and luminal fluid from the early, mid, and late proximal tubule (E, M, and L PT). Samples were collected from euvolemic Munich Wistar rats by free-flow micropuncture; ANG concentrations were measured by RIA. In one group of rats, concentrations of total immunoreactive ANG (reflecting ANG II and lesser amounts of three fragments) in GF and E, M, and L PT fluid averaged 29-40 nM compared with 32 pM in systemic plasma. In a second group, immunoreactive ANG concentrations in SVP also exceeded systemic levels by a factor of 1,000. In a final group, samples of GF and LPT fluid were purified by HPLC before RIA to measure ANG II and III concentrations specifically: their respective concentrations were 6-8 nM and 14-25 nM. We interpret these results to indicate that substantial amounts of ANG peptides are released into or generated within intrarenal fluid compartments, in which local ANG is likely to effect regulation of renal function independently of systemic ANG. PMID- 2212019 TI - Sensibility and cutaneous reinnervation of pectoralis major myocutaneous island flaps. A preliminary clinical report. AB - The cutaneous sensibility of 13 pectoralis major cutaneous island flaps has been investigated retrospectively. Although in raising the pectoralis major myocutaneous island flap sensory denervation of the skin is produced, after a mean follow-up period of 29 months (range 5 to 71 months), 68% of the cutaneous portion of the flap revealed sensibility to touch, suggesting a reinnervation from the surrounding intact oral mucosa or skin. The rate of reinnervation was found to be related to the sensibility present in the surrounding tissue. PMID- 2212018 TI - Platelet alpha-granule fibrinogen, albumin, and immunoglobulin G are not synthesized by rat and mouse megakaryocytes. AB - It has been assumed that endogenous synthesis by the platelet precursor cell, the bone marrow megakaryocyte, is the major source of platelet alpha-granule protein. To test this hypothesis, we used mRNA phenotyping to detect in megakaryocytes the presence of mRNA transcripts specific for various proteins. Our results indicate that megakaryocytes synthesize platelet factor 4, a protein relatively specific for platelets, but do not express mRNA transcripts for the fibrinogen, albumin, or IgG found in alpha-granules. We have previously shown that megakaryocytes endocytose circulating proteins, including fibrinogen, albumin, and IgG, and incorporate them into alpha-granules. Thus, platelets appear to contain a unique type of secretory granule whose contents originate by both endogenous synthesis and endocytosis from plasma. Under basal conditions, the source of alpha-granule fibrinogen is plasma. PMID- 2212020 TI - Peripheral streptomycin/lidocaine injections versus lidocaine alone in the treatment of idiopathic trigeminal neuralgia. A double blind controlled trial. AB - Seventeen patients with long-lasting idiopathic trigeminal neuralgia (ITN) were treated with either five, weekly peripheral streptomycin/lidocaine (S/L) or lidocaine alone injections, in a double blind controlled study. Eight patients responded initially to the treatment in the S/L group and three patients in the lidocaine group. Pain recurred in four patients from the S/L group within two weeks and six months following the last injection. One patient from the lidocaine group remained pain-free for eight months. At the final assessment, three patients from the S/L group and two patients from the lidocaine group remained pain-free up to 30 months. Neither treatment affected sensory functions of the injected nerves. It is concluded that S/L injections are initially effective in the treatment of ITN. In the long term, however, their effects are similar to the effects of lidocaine alone. PMID- 2212021 TI - Ameloblastic carcinoma of the maxilla metastatic to the mandible. Case report. AB - A case of maxillary ameloblastic carcinoma metastatic to the mandible is presented. Of 33 cases of ameloblastic carcinoma reported in the English literature 10 have occurred in the maxilla. Of these, none produced mandibular metastases. The authors review the literature, describing clinical presentation, histological appearance, and treatment of this rare lesion. PMID- 2212022 TI - The pattern and aetiology of maxillofacial injuries in Greece. A retrospective study of 25 years and a comparison with other countries. AB - In comparison with other countries, Greece demonstrates a high incidence of road traffic accidents (RTA's). Most are the result of violation of the highway code. Violence as a causative agent of fractures of the facial skeleton is still a minor factor in comparison with other countries. Most of the people involved are young. In a 25-year period we have treated 6,847 fractures of the facial skeleton. Fractures of the mandibular condyle, the genial symphysis and the zygomatico-maxillary complex were the most numerous. 25% of the patients were women and 75% men. 56% were treated conservatively; an open reduction was the treatment of choice in 37%, while no treatment was considered necessary in 7%. In the period under study, K.A.T. Hospital admitted 60% of the maxillofacial trauma in the whole country. PMID- 2212023 TI - Maxillofacial fractures related to work accidents. AB - Work-related maxillofacial fractures were studied retrospectively over a six-year period. There were 98 cases accounting for 4.5% of all facial bone fractures treated in our hospital between 1981 and 1986. Of the patients, 89.8% were male. The mean age of the injured was 36.4 years. The incidence of work-related maxillofacial fractures was 0.37 per 1000 workers. Most of the injuries (66%) occurred in factories and construction work. Such work was associated with an to 15 times higher risk of maxillofacial fracture than service and office work. Of the fractures, 20.4% were sustained on the way to or coming from work. At the place of work, the commonest causes of injury were blows from objects or falls from a height (70%). On the way to or coming from work, the aetiological factor was most often a traffic accident. Assault and battery had caused facial bone fractures in 11.2% of cases. Fifty-five patients with midface and 45 patients with mandibular fractures were found, of these, 8 patients had bimaxillary fractures. In 6 cases, only dentoalveolar fractures were found. Of the patients, 55.1% were treated operatively. Sixty-six patients were hospitalized, the mean length of hospital stay being 3.2 days (range 1-12 days). PMID- 2212025 TI - Ultrasonographic evaluation during reduction of zygomatic arch fractures. AB - Ultrasonography was utilized in three cases of zygomatic arch fracture to confirm the position of the fragments during surgery. Ultrasonography revealed the nature of the fracture clearly and real-time imaging aided its reduction. Accordingly, ultrasonography is considered to be useful to confirm the position of fragments of the zygomatic arch during reduction. PMID- 2212024 TI - Sagittal fracture of the maxilla. AB - Although sagittal fractures of the maxilla are not common, they can be observed in some cases following severe trauma to the facial skeleton. 18 of the 23 cases reported had combined mandibular and midfacial fractures. Sometimes in severe cases they may demonstrate instability with conventional methods of treatment; thus for adequate stabilization they may need a palatal splint, direct wiring (internal fixation in the buttresses), intermaxillary fixation and cranial suspension. PMID- 2212026 TI - Planning and control of vertical dimension in Le Fort I osteotomies. AB - Depending on the different anatomy of the soft and hard tissues, concavity or convexity of the face, measurements of inferior or superior repositioning of the maxilla may be less predictable when using only the osteotomy site for this calculation. A more reliable method would be to measure the distance from a bone mark in the forehead to the incisor edges. This method has been practiced by our clinic during the past five years. The method is thought to offer a more accurate estimation of the position of the upper anterior teeth in relation to the lip, although one must anticipate a certain degree of postoperative relapse especially concerning inferior repositioning. In order to evaluate the accuracy of our method, a comparison has been made of the calculated vertical repositioning and the surgical results in two groups. In group I (12 individuals) conventional estimation of maxillary repositioning in the osteotomy line was made; in group II (12 individuals) measurements were made from a bone mark on the forehead to the incisor edges. A satisfying correlation was found between calculated and achieved results in both groups. In comparison between calculated and immediate postoperative measurements the results showed no statistically significant difference between the two methods. PMID- 2212027 TI - Regeneration of cranial suture and bone plate lesions in rabbits. Implications for positioning of osteotomies. AB - The positioning of osteotomies in intramembranous cranial bone was studied by exploring the pattern of bone regeneration in growth areas (the sutural region) as compared to that of the bone plate proper. Trephine defects in the left coronal suture area and the right parietal bone were produced in fifty-nine young rabbits. A pilot study to refine operative and analytical methods comprised 22 animals. The experiments were terminated at one, three, and six weeks after surgery. The bone regenerative response was assessed by x-ray planimetry, plain microscopy, enzyme histochemistry, and fluorescent labelling. Only minor divergences in healing capacity between the two defects were found. No adverse effects on the growth process were indicated. As to clinical management, the findings suggest that osteotomies designed to traverse sutural areas will, under normal circumstances, regenerate in a similar manner and rate to adjoining bone plates. PMID- 2212028 TI - Mandibular distraction. An experimental study on sheep. AB - In a series of 17 growing sheep (aged 13.5-19 weeks) the recently developed external fixation frame permitting gradual distraction, was tested. The frame gives good stability during distraction. Mandibular osteotomy was performed transversely in the middle of the ramus, under general anaesthesia, with an oscillating saw. Using distraction by approximately 1 mm per day, lengthening of the mandibular ramus was achieved. X-ray analysis showed all the distracted osteotomies to have healed in 25 days, showing new bone formation in the distraction gap. The pattern of radiological healing was graded according to the phase of consolidation. With this method it appears to be possible to lengthen the mandible without transplantation of additional bone. PMID- 2212029 TI - Pediatricians' perceptions of their behavioral and developmental training. AB - Eighty graduates of a pediatric residency that required training in behavior and development completed a survey of their perceptions regarding the quality of this training, the utility of behavior and development for modern pediatric practice, their competence in applying behavior and development knowledge, and their desire to pursue additional training in behavior and development. Surveys were completed 1 to 5 years (mean = 3.4 years) after graduation from the residency program. Graduates consistently rated child development and anticipatory guidance/counseling as the areas that were best taught, most useful, and in which they felt the most competent. The highest ratings of behavioral/developmental pediatrics (BDP) competence and usefulness were from graduates who received additional BDP training after residency. However, a large percentage of graduates did not endorse the usefulness of several dimensions of behavior and development that have been considered integral components of training. Implications and limitations of the present study are discussed. PMID- 2212030 TI - Mental efficiency and hypoglycemia. AB - Cognitive functioning after a mild hypoglycemic episode (MHE) was studied in 24 school-age children with insulin-dependent diabetes mellitus (IDDM). All children were administered a battery of neuropsychological tests which included digit spans, trailmaking tasks, Klove Mathews Maze test, and finger-tapping and handwriting tasks. The experimental group (n = 14) consisted of children who were tested initially after resolution of hypoglycemic symptoms following a documented MHE (Chemstrip bG less than or equal to 60 mg/dl with symptoms). The comparative group (n = 10) consisted of children who were initially evaluated after documentation of euglycemia. Comparison of the comparative group scores with test scores of the experimental group after recovery from the MHE demonstrated statistically significant differences (p less than 0.05 by dependent t-tests) in five of 12 tasks. No differences were noted when second trial scores of both groups were compared when they were retested after documentation of euglycemia. This study suggests that a discrepancy exists between the recovery rate of physical symptoms and cognitive function in children following a MHE. PMID- 2212031 TI - Outcomes and parent-child relationships of former adolescent mothers and their 12 year-old children. AB - This study compared former adolescent mothers and their 12-year-old children with adult child-bearing mothers and their children along three dimensions: mothers' life-course characteristics (e.g., educational attainment, employment status, current annual family income); children's scholastic, psychological, social, and behavioral adjustment; and dimensions of the parent-child relationship (e.g., companionship, affection, intimacy). Results showed that adolescent mothers had significantly lower levels of completed education than adult mothers, and children of teenage mothers exhibited more learning problems (as rated by self, mother, and teacher) than children of adult mothers. Younger childbearing mothers and fathers felt they provided less esteem enhancement support to their children than older childbearing parents. In addition, early childbearing mothers felt less satisfied with their mother-child relationships, and early childbearing fathers shared fewer companionate activities with their children than adult childbearing mothers and fathers, respectively. The long-term implications of adolescent parenting for the adolescent and her child are discussed. PMID- 2212033 TI - The use of methylphenidate in a depressed adolescent with AIDS. AB - Stimulants once used to treat depression have been overshadowed by tricyclic antidepressants and monoamine oxidase inhibitors. Recently, their use has been reported in the treatment of depression in medically ill adults in whom tricyclics are contraindicated, or for whom a rapid response is critical. This report documents the successful use of methylphenidate in a depressed adolescent with AIDS. PMID- 2212032 TI - Maternal depressive symptoms during pregnancy, and newborn irritability. AB - Maternal depression is associated with a wide range of adverse outcomes for children, including poor mother-infant interactions at 3 months post-partum. The aim of this study is to determine whether maternal depressive symptoms during pregnancy are associated with neonatal neurobehavioral functioning, as measured by the Neurologic and Adaptive Capacity Scale. The study population consists of 1,123 mothers and their term infants who were participants in a larger study of maternal health and infant outcomes. Women were administered the Center for Epidemiologic Studies-Depression (CES-D) questionnaire for depressive symptoms during their pregnancy. Their infants were subsequently assessed by a pediatrician blind to their CES-D scores. The CES-D score was associated with unconsolability and excessive crying (p less than 0.01). The higher the mother's CES-D score, the more likely it was that the infant would be unconsolable or cry excessively. Mothers with CES-D scores at the 90th percentile were 2.6 times more likely to have unconsolable newborns, compared with women with CES-D scores at the 10th percentile (95% C.I. = 1.54, 4.23). When potentially confounding variables, such as cigarette smoking, alcohol, marijuana, and cocaine use, poor weight gain, income, birth weight, and other drug use, were controlled, the relationship between CES-D score and newborn unconsolability and excessive crying remain unchanged. The results of this study suggest that the relationship between early childhood problems and maternal depressive symptoms may be part of a sequence that starts with depressive symptoms during pregnancy. PMID- 2212034 TI - Training pediatricians in family therapy. PMID- 2212035 TI - Psychosocial risk and protective factors in childhood. PMID- 2212036 TI - Psychosocial risk factors in childhood: what can the pediatrician in practice do? PMID- 2212037 TI - Developmental outcome, at age 3 and 4 years, of children exposed in utero to alcohol, tobacco, and marijuana. PMID- 2212038 TI - Meanings of death and intrinsic religiosity. AB - The objective of this study was to simplify understandings of relationships between multidimensional elements of the fear of death and dying with a unidimensional construct of intrinsic religiosity. A total of 346 individuals who ranged in age from 18 to 88 completed a death anxiety scale and a measure of intrinsic religious motivation. Respondents who were older and who were higher in intrinsic religiosity were significantly lower in death anxiety. Differing constructions of death and dying are examined. PMID- 2212039 TI - Use of the MMPI to uncover histories of childhood abuse in adult female psychiatric patients. AB - Psychiatric hospital records of 182 adult females were reviewed to determine feasibility of using the MMPI to uncover repressed histories of childhood abuse. Charts with MMPI profiles that met the standard and extended Scarlett O'Hara V configurations were examined for histories of childhood sexual or physical abuse and exposure to parental alcoholism. Findings were compared with a representative sample of control patients who did not have Scarlett O'Hara V configurations. Results showed that the MMPI can help detect adults who as children were sexually or nonsexually abused, or had alcoholic caretakers, or a combination of the above. PMID- 2212040 TI - Distorted body image in normal college women: possible implications for the development of anorexia nervosa. AB - College women (N = 100) who averaged about 18 years of age were asked to rate the size of their bodies after looking in a mirror, and these ratings were compared to their actual body sizes. Women whose personality characteristics more closely resembled those proposed as basic to anorexic development in Slade's model were more inclined to overestimate body size, but only if they were relatively thin. A motivational role for body-image overestimation was suggested wherein this distortion serves to maintain dieting behavior even when a thin body is attained. PMID- 2212041 TI - The relationship between life events and mental health in homosexual men. AB - In a study to determine the extent to which stigmatization influences mental health in homosexual men, 80 homosexual men were administered the General Health Questionnaire and the Gay Affect and Life Events Scale. Data indicated that there were significant associations between life events and mental health; events related to AIDS had the highest correlations. However, general life event scales that included Finances and Work also were associated significantly with mental health, as previously reported in the general population. These data suggest that the impact of life events may be amplified by stigmatization and that degree of life change is associated closely with psychological dysfunction. It is concluded that life events that are related to both stigmatization and life change and related emotional distress are significant predictors of psychology dysfunction. PMID- 2212042 TI - A factor analysis of Ellis' irrational beliefs. AB - In an effort to identify, organize, and operationally define the philosophies that underlie Albert Ellis' self-defeating beliefs, the authors factored an 11 item irrational-values self-report instrument given to 190 psychiatric patients. Four factors emerged and were named to reflect the contents of their items--"I need to control a dangerous world," "Self-assertion is painful," "I need affirmation," and "I lack control over my fate." PMID- 2212043 TI - Sense of coherence, life stress, and psychological distress: a prospective methodological inquiry. AB - Antonovsky (1987) has proposed the Sense of Coherence (SOC) as a global perceptual predisposition in responding to life stress. Composed of comprehensibility, manageability, and meaningfulness, this construct has been associated with more adaptive coping in previous cross-sectional studies. This prospective study (N = 95) investigated the association of SOC (assessed by Antonovsky's measure) with life stress and symptoms. SOC was correlated negatively with life stress and symptoms and appeared to mitigate the impact of life stress. SOC was not found to be a buffer variable. Implications of these findings are presented, as are methodological issues that concern Antonovsky's measure. PMID- 2212044 TI - Factor structure of the Edwards personal preference schedule in a vocational rehabilitation sample. AB - The 15 scales of the Edwards Personal Preference Schedule were factor analyzed for 450 male and 89 female vocational rehabilitation clients in order to compare results by gender as well as combining them to compare with the college norming data in the EPPS manual. Correlations and factors were similar in many ways when the combined sample and norm samples were compared, but larger and consistent differences between the study scores suggest that separate norms are justified and that norm tables need to be revised. PMID- 2212045 TI - Composite descriptions associated with rare MMPI two-point code types: codes that involve scale 5. AB - MMPI files of 1,016 prior patients were searched for protocols with two-point codes that involved scale 5. Sixty-one such protocols were found; these accounted for 6% of the sample. Salient characteristics of the cases were noted, and composite descriptions were developed for each of the code types. An additional 22 cases were located over the next 2 years in response to my requests for such profiles. Base rates from the original sample, as well as descriptive statistics and composite descriptions from the extended sample, are provided for each of the eight code types with the exception of the 5-0/0-5 code, which will be presented elsewhere. PMID- 2212046 TI - Assessing the validity of memory complaints: performance of brain-damaged and normal individuals on Rey's task to detect malingering. AB - Rey (1964) proposed a brief screening test to assess the validity of memory complaints and hypothesized that the ease of the task would mislead malingerers to perform more poorly even than persons with impaired memory due to brain injury. Lezak (1983) suggested cut-offs, but only one empirical report on Rey's task could be located in the literature. That study by Goldberg and Miller (1986) supported Lezak's cut-offs; however, the criterion groups were psychiatric and mentally retarded inpatients. In the present study, Rey's test, along with other neuropsychological tests designed to determine various types of memory dysfunction, was administered to brain-damaged (n = 18) and comparison (n = 16) groups. The results again generally supported Lezak's cut-offs. PMID- 2212047 TI - Prediction of verbal, performance, and full scale IQs from seven subtests of the WAIS-R. AB - The Wechsler Adult Intelligence Scale-Revised (Wechsler, 1981) was given to 70 male VA patients, and IQs were estimated from seven subtests that require about half the administration time of the full test. Estimates correlated well with Verbal, Performance, and Full Scale IQs, and mean estimated IQs differed by less than 1 IQ point from actual means. Error sizes in predicting Full Scale IQs were small (M = 1.96) and exceeded 4 IQ points in only 3 cases. In comparison, error sizes for the Doppelt (1956) abbreviation (M = 3.71) were significantly larger and were greater than 4 IQ points in 20 cases. PMID- 2212048 TI - Interpersonal behavior profiles of eight cases of DSM-III personality disorder. AB - The present study used ratings of patients' interpersonal behaviors by groups of clinical trainees and undergraduates to test a priori classifications of DSM-III personality disorders onto the 1982 Interpersonal Circle. A sample of 8 videotaped personality disorder patient interviews were obtained from two psychiatric training tape series. A panel of 10 diagnosticians provided independent checks on the diagnosis assigned to the 8 patients by the training series and also rated the degree of prototypicality each case exhibited. Interpersonal characterizations of the interview behavior of the 8 patients were obtained from ratings of the tapes by undergraduate and clinical trainee observers. Findings revealed that interpersonal inventory ratings significantly differentiated the overt interpersonal behavior of the 8 patients, although the obtained interpersonal profiles appeared more complex and subtle than previous interpersonal translations suggest. PMID- 2212049 TI - Does FIRO-B relate better to interpersonal or intrapersonal behavior? AB - After meeting for 33 hours over 7 weeks, 64 undergraduates from 11 small interpersonal skills groups rated themselves on Schutz's (1958) Fundamental Interpersonal Relations Orientations-Behavior (FIRO-B). Three weeks and 17 more group interaction hours later, they also described each same-group participant, including self, on Lorr and McNair's (1963) Interpersonal Behavior Inventory (IBI). Correlations between self-ratings on 6 FIRO-B and 15 IBI scales yielded 25 significant statistically (p less than .05) values, but merely 5 among FIRO-B's 90 parallel correlations with individual's mean IBI ratings from pooled small group peers. Of all 30 significant correlations, 19 linked FIRO-B's overlapping affection and inclusion measures positively, but narrowly, with 4 IBI scales that address affiliativeness/sociability. The findings challenge Schutz's (1958) paradoxical claim that FIRO-B validly assesses interpersonal behavior by an intrapersonal method. PMID- 2212050 TI - Sex, sex role identification, and college students' projective drawings. AB - A study of 109 undergraduates found that sex and sex role identification, as assessed by the Bem Sex Role Inventory (BSRI), were related significantly to sex sequence, sexual differences, and quality of drawing on the Draw-A-Person (DAP). Specifically, males and masculine persons tended to draw males first, female and feminine persons tended to draw females first, and androgynous persons were equally likely to draw a male or a female first. The greater the sexual differentiation of the female human figure drawing, the lower the subject's degree of masculinity. The single best predictor for identifying a female subject was the quality of the female figure drawing. Results were consistent with Machover's hypothesis that drawings of the human figure reveal facets of the subject's self-image. PMID- 2212051 TI - Effect of social class of subjects on normative responses to TAT cards. AB - The present study investigated whether there are significant differences in the responses of individuals of varied social class background to selected TAT cards. White, female college students (N = 70) were classified as "working class" or "middle class" according to the characteristics of their families of origin and were asked to write stories in response to five TAT cards. Significant differences between the TAT stories written by the two social class groups were found for pattern of dependency and locus of control. No significant differences were found in number of drive expressions, intensity of drive expressions, or level of defenses used. Implications of these results for testing, as well as the difficulties in studying psychological phenomena across social class, are discussed. PMID- 2212052 TI - Adolescents who kill. AB - From a sample of 1,956 adolescent delinquents referred to us by the court for physical, psychological, psychiatric, educational, and social examinations, 71 delinquents convicted of homicide were matched with 71 nonviolent delinquents by age, race, sex, and socioeconomic status (SES). These two groups were compared on the basis of these evaluations by stepwise discriminant analysis, matched pairs, two-tailed t-tests, and nonparametric tests. Adolescents who kill have a tetrad of symptoms: (1) criminally violent family members; (2) gang membership; (3) severe educational difficulties; and (4) alcohol abuse. PMID- 2212054 TI - The effectiveness of various degrees and circumstances of program completion of young male offenders in a residential treatment center. AB - Boys admitted to a treatment facility do not always complete their treatment. This study analyzes the follow-up socialized coping of boys preponderantly classified as conduct disordered who were admitted to a residential treatment center. The boys were categorized into 10 different groups, only 1 of which consisted of those who actually completed treatment. The differences between groups and subsequent coping were fairly pronounced and highly significant. Further analysis indicated that very few of the group differences could be attributed to either age at admission or duration of treatment. Data analysis supported the hypothesis of treatment effectiveness in that boys who completed treatment did better in general than boys who did not, although those withdrawn by their parents did best of all. Furthermore, the rather pronounced differences among groups that failed to complete treatment raised certain methodological questions with regard to the practice of aggregating such groups in evaluation research. PMID- 2212053 TI - Situational variability in boys and girls identified as ADHD. AB - The present investigation (N = 60) examined HSQ and SSQ (Home Situations Questionnaire/School Situations Questionnaire) protocols across individual items and recently developed factoral dimensions. The purpose was to assess the degree to which situational variability in behavior may prove sensitive to sex differences in ADHD children. Results did not support clear gender differences in children identified as ADHD. PMID- 2212055 TI - Interpersonal types among alcohol abusers: a comparison with drug abusers. AB - Interpersonal types among alcohol abusers were examined with Calsyn, Roszell, and Anderson's (1988) nine-type system for classifying FIRO-B profiles. The frequencies of the nine FIRO-B types among a sample of 135 male veteran alcohol abusers were compared with Calsyn et al.'s (1988) previously published data for a sample of male veteran drug abusers, a normative veteran sample, and a general population sample. The alcohol abusers, like Calsyn et al.'s sample of drug abusers, were more likely to be categorized as "loners," "rebels," and "pessimists" than was the general population sample. While exhibiting preferences for interpersonal types that emphasized social withdrawal, avoidance of responsibility, and mistrust of others, both the alcohol abusers and the drug abusers were heterogeneous groups whose members demonstrated a variety of interpersonal types. PMID- 2212056 TI - The construct validity of an aftereffect-based subtyping system for alcoholics. AB - In an earlier project, we identified five alcohol-consumption aftereffect factors, which were named Hangover, Euphoria, Flushing, Seizures, and Sleepiness. In this study (N = 100) we assessed the construct validities of the five, using 47 MMPI, self-report, and recidivism criteria. The number of significant relationships between the factors and the criteria substantially exceeded chance. The Hangover factor related to social maladjustment and to the MMPI Psychopathic Deviate, Paranoia, Psychasthenia, Hypomania, and Masculinity-Femininity scales. The Euphoria factor was associated with a high number of job losses, but a low incidence of certain physical sequelae. The Flushing factor was associated with high consumption, late development of alcoholism, many physical complaints, and older age. The Seizure factor correlated with high consumption, facial puffiness, tremors, and lack of defensiveness on the MMPI. The Sleepiness factor was associated with a good prognosis and several mild MMPI elevations. These findings suggest that the factors may provide the basis for a useful alcoholism subtyping system and that additional research on them should prove fruitful. PMID- 2212057 TI - Differences in family functioning among bulimics, repeat dieters, and nondieters. AB - This article examined bulimics' (n = 31) perceptions of how their families function relative to a group of women at risk for developing bulimia (repeat dieters) (n = 61) and a group not at risk for an eating disorder (nondieters) (n = 59). The results indicated that bulimics perceive their families to be more dysfunctional than do repeat dieters or nondieters. The bulimics reported poorer general family functioning, more affective involvement, less affective responsiveness, poorer family communication, poorer problem-solving skills, and poorer behavior control. The hypothesis that repeat dieters would evidence more family dysfunction relative to the nondieters was not supported. The results are discussed in terms of how family variables may contribute etiologically to bulimia. PMID- 2212058 TI - The roles of clinical psychologists: a comparison of faculty models and student practicuum roles. AB - This article focuses on the definition of faculty education and training models, as compared to student field placement job roles. Both faculty models and student roles are described in terms of tasks and job skills that were judged important. An inverse factor analysis was performed for the task importance judgements, separately for the faculty sample and the student sample. Group membership was used to calculate both task and job skill profiles. Those profiles were compared to determine the similarities and differences between the faculty and student models. Overall, there is a lack of similarity between faculty members' education and training models and student field placement job roles, as identified by the multidomain job analysis technique. One must conclude either that the faculty models represent a developmental view, rather than the current reality as represented by field placement jobs, or that those jobs are artificial roles that are irrelevant insofar as education and training are concerned. PMID- 2212059 TI - Aspects of consensus in clinical predictions of imminent violence. AB - This research studied individual differences among psychiatric patients in the extent to which clinical workers agree about the likelihood that the patients will act violently. Predictions of imminent violence proneness for 40 male inpatients made by 35 experienced clinical practitioners were analyzed. As hypothesized, subgroups of patients who elicited high interjudge agreement were found, and admission profiles of these patients were presented. Clinical workers' predictive accuracy was found to be greater when they rated patients who elicited high consensus than for unselected patients or for those who elicited low consensus. PMID- 2212060 TI - Willingness to apply understood ethical principles. AB - Recent research suggests a discrepancy between understanding vs. implementation of ethical principles. The present study investigated the relationship between decisions with regard to what "should" vs. what "would" be done in a variety of ethical conflict situations. Additionally, this research examined the influence of the degree of closeness of the respondent to the identified person-of reference in each conflict scenario. The results strongly supported the conclusion that while professional clinicians are capable of recognizing conduct that falls below accepted ethical standards, they are less willing to follow through with required action. Restrictiveness of conflict resolution was related to both person-of-reference group and to specific ethical situation. The results are discussed in terms of attribution theory and actor-observer effects. PMID- 2212061 TI - Pathology across Europe: differences and similarities. 2. Microbiology. PMID- 2212062 TI - Guidelines on the investigation and management of thrombophilia. The British Committee for Standards in Haematology. PMID- 2212063 TI - Specimen transport audit. AB - A specimen transport audit was performed at a routine and reference laboratory. Over the survey period (1986-89) the percentage of specimens received and assessed as hazardous (inadequately packed, misidentified, or contaminated by leakage) fell significantly from 12.0 to 2.8%. Specimen transport audit identified technical and logistical faults associated with sample transmission. It is concluded that no type of hazard should exceed 0.5% of samples, with the total being less than 1% of specimens received. Specimen transport audit is an additional laboratory performance indicator. PMID- 2212064 TI - Use of monoclonal antibody KP1 for identifying normal and neoplastic human mast cells. AB - The monoclonal antibody KP1 (CD68) was used to stain normal and neoplastic monocytes and macrophages in routinely processed, paraffin wax embedded tissue: mast cells also exhibited strong, consistent cytoplasmic immunoreactivity. Light microscopic findings were corroborated by electron microscopical and immunocytochemical findings. The predominant sites of immunoreactivity were the specific intracytoplasmic granules of the mast cells. All mast cell subtypes- that is, normal and reactive mast cells, such as those in lymph nodes exhibiting chronic non-specific lymphadenitis, and malignant or neoplastic mast cells in various types of mastocytosis--reacted with this antibody. This finding is of diagnostic importance, because mast cell proliferation could be mistaken for histiocyte proliferation. It also supports the hypothesis that mast cells derive from the bone marrow. PMID- 2212065 TI - Testicular sex cord stromal tumour with granulosa cell differentiation: detection of steroid hormone receptors as a possible basis for tumour development and therapeutic management. AB - A testicular sex cord stromal tumour with granulosa cell differentiation, typical of granulosa cell tumours of the adult type, was investigated immunohistologically on snap frozen and paraffin wax embedded material. The predominance of vimentin and the additional expression of cytokeratin subtypes 8 and 18, as well as the negative staining for epithelial membrane antigen, accorded with results previously reported, for ovarian granulosa cell tumours; the lack of expression of desmoplakin, however, was a distinctive feature. Together with negative staining for leucocyte common antigen, the antigen pattern facilitates the differential diagnosis between granulosa cell tumour and undifferentiated carcinoma or gonadal lymphoma, although its suitability for differentiating within the group of gonadal stromal tumours seems to be limited. The small growth fraction, shown by the monoclonal antibody Ki-67, is typical of the clinical behaviour of granulosa cell tumours. The expression of oestrogen and progesterone receptors, also recently found in testicular Leydig cell tumours, may provoke new approaches to the management of testicular granulosa cell tumours, as well as a new hypothesis on the development of these tumours. PMID- 2212066 TI - Immunohistochemical detection of abnormal cell proliferation in colonic mucosa of subjects with polyps. AB - Previous studies have shown the presence of increased proliferation in the large bowel epithelium of those at high risk of developing colon cancer. An in vitro technique for labelling large bowel mucosa with the thymidine analogue bromodeoxyuridine (Brdu) was therefore developed and its ability to distinguish differences in mucosal proliferation between subjects with colorectal adenomas and normal controls was assessed. Sigmoid biopsy specimens from 15 subjects with polyps and 15 age and sex matched controls were labelled and the incorporated Brdu visualised with an immunohistochemical technique. Mean labelling index (LI) was significantly higher in those with polyps than in controls. Differences in the pattern of labelling in colonic crypts were compared by the generation of cumulative labelling distributions. Analysis showed a significant expansion of the proliferative compartment in the colon crypts of those with polyps. It is concluded that in vitro labelling with Brdu provides a useful method for the assessment of mucosal proliferation in subjects at high risk of developing colon cancer. PMID- 2212067 TI - JC70: a new monoclonal antibody that detects vascular endothelium associated antigen on routinely processed tissue sections. AB - A new monoclonal antibody, JC70, raised against a membrane preparation from a spleen affected by hairy cell leukaemia, recognises a membrane bound glycoprotein identical with that of the CD31 group of monoclonal antibodies. The antibody stains a fixation resistant epitope on endothelial cells in benign and malignant conditions in a wide variety of paraffin wax embedded tissue. JC70 stained malignant endothelial cells in 10 angiosarcomas with more consistency than monoclonal or polyclonal antibodies to factor VIII related antigen (FVIII-Rag). In four cases of Kaposi's sarcoma the antibody stained malignant endothelial cells but not spindle cells. It is concluded that antibody JC70 is of value for studying benign and malignant human vascular disorders in routinely processed tissue. PMID- 2212068 TI - Antigen specific serum antibody response to Chlamydia trachomatis in patients with acute pelvic inflammatory disease. AB - Sera from 35 patients with acute pelvic inflammatory disease (PID) with and without Chlamydia trachomatis confirmed by culture and sera from 19 control patients with neither evidence of pelvic infection nor C trachomatis infection were studied for the presence of serum IgG, IgA, and IgM antibodies to C trachomatis using enzyme immunoassay (EIA) and immunoblotting techniques. There was no correlation between the antibody concentrations in the EIA and the spread of chlamydial infection, as determined by cervical, endometrial, and laparoscopic sampling for chlamydia. The immunoblot analysis showed antibodies to the major outer membrane protein (MOMP) of C trachomatis elementary bodies in all patients who had had C trachomatis isolated. Reactivity was also frequently observed against the 68, 62, 60, 45, and 31 kilodalton antigens. About 20 antigenic polypeptides were identified. Differences in antibody prevalence to specific chlamydial antigens, however, were not related to the site of chlamydial isolation or serum antibody concentrations observed with the EIA. The results indicate that patients with PID with and without upper genital tract infection with C trachomatis cannot be differentiated by reactivity of sera to specific chlamydial polypeptide antigens. The determination of a specific serum IgA antibody response by EIA was the most effective single test to discriminate between patients with and without acute chlamydial infection. PMID- 2212070 TI - Latex enzyme immunoassay for measuring IgG antibodies to rubella virus. AB - A latex enzyme immunoassay (LEIA) for detecting IgG class antibody to rubella virus was compared with the latex agglutination test (LA) and a haemagglutination inhibition assay (HI). Of 243 sera tested, four discrepant results were observed among all three techniques, corresponding to borderline values. Except for one sample containing specific IgM class antibody, the difference between quantitative results from each pair of tests was always within a value corresponding to two doubling dilutions and was considered to have acceptable variation. The LEIA technique allowed 10 seroconversions to be detected, as determined by the other techniques. The LEIA required a single 1 in 8 sample dilution, took 30 minutes, and provided a useful alternative assay for the quantitation of rubella antibodies. PMID- 2212069 TI - Serum pepsinogen I and gastrin concentrations in children positive for Helicobacter pylori. AB - Serum pepsinogen I, serum gastrin concentration, and inflammatory scores were measured in a population of 71 children undergoing upper gastrointestinal endoscopy for investigation of upper abdominal pain. Forty four were initially colonised with Helicobacter pylori. The indices were measured before treatment (in 71 children), one month (in 41 children), and six months (in 21 children) after stopping treatment. Before treatment there was a significant correlation between serum pepsinogen concentration, total inflammatory score, and H pylori state, but no correlation between serum gastrin concentrations and H pylori state. Similarly, the total inflammatory score and serum pepsinogen concentrations were significantly correlated. There was no such correlation in children negative for H pylori. After treatment the inflammatory score improved in those patients in whom H pylori had been eradicated. There was also a significant fall in serum pepsinogen I and serum gastrin concentration in those patients in whom H pylori had been eradicated. These results were similar to those found six months after treatment had been stopped. These findings suggest that the serum pepsinogen I concentration could be considered a useful marker for gastritis and can be used as an index of severity of gastritis in H pylori positive subjects. The measurement of serum gastrin concentrations does not give useful information. PMID- 2212071 TI - Use of urea filter paper disc to detect urease activity in Enterobacteriaceae by multipoint replication techniques. AB - A new method of detecting urease activity in Enterobacteriaceae was developed. An 8.5 cm filter paper disc impregnated with 20% urea and 0.5% bromocresol purple was placed on the surface of a glucose fermentation plate after inoculation with a multipoint replicator and overnight incubation. This method was compared with the commercially prepared Mast urea agar (Multipoint) and Fuscoe's Urea Plate Medium. A total of 240 routine isolates of Enterobacteriaceae were tested for urease activity using the three methods. Sixty five isolates were positive by the three methods while 33 isolates gave differing results. The urea disc method was more sensitive for detecting urease activity in isolates of Klebsiella species, Morganella morganii, and Yersinia enterocolitica. It also overcame the problem associated with the other two media of diffusion of alkali end products through the medium. PMID- 2212072 TI - Multiple breakpoint method for measuring effect of antibiotics on endocarditis strains of streptococci. AB - The activity of penicillin alone and combined with aminoglycoside on endocarditis strains of streptococci was examined. Good assay reproducibility was obtained by the use of logarithmic phase cultures standardised by opacity, careful inoculation of well-plates, removal of antibiotic by membrane transfer and incubating survival counts in hydrogen plus carbon dioxide. The use of 10-fold intervals for penicillin concentration simplified assay design without loss of efficiency. PMID- 2212073 TI - Effect of sample volume on yield of positive blood cultures from adult patients with haematological malignancy. AB - Six hundred and sixteen blood samples from patients with haematological malignancy were each distributed equally among three identical cells in a Malthus Microbiological Growth Analyser. The mean (SD) volumes inoculated into sets in which one, two, or three of the three bottles were positive were 37.7 (10.1) ml, 37.4 (12.9) ml, and 37.7 (10.5) ml, respectively. Overall, clinically important organisms were isolated from one bottle only with 18 cultures, from two bottles only with 19 cultures, and from all three bottles in a set with 104 cultures. If the yield from a single bottle inoculated with a mean volume of 12.6 ml blood is taken as 100%, the yield from 25.2 ml in two bottles was 110.7% and the yield from 37.7 ml in three bottles was 115.6%. The increased yield from increased volume was considerably lower than that reported from unselected groups of patients, which suggests that the magnitude of bacteriaemia is greater in patients with neutropenia. The isolation of infecting organisms from the blood of patients with neutropenia is, however, particularly important in directing chemotherapy and consequently 45 ml blood samples from these patients continue to be requested. PMID- 2212074 TI - True lipoma of Glisson's capsule. PMID- 2212075 TI - Benign lymphoepithelial lesion of salivary gland in a patient with AIDS. PMID- 2212076 TI - Acinetobacter spp L-form infection of a cemented Charnley total hip replacement. PMID- 2212077 TI - Fibrinogen standards. PMID- 2212079 TI - Anti-HBc IgM assays and diagnosis of acute hepatitis B. PMID- 2212078 TI - Necrotising lymphadenitis without granulocytic infiltration: case from Western Samoa. PMID- 2212080 TI - Potential benefit of 1-alpha-cholecalciferol in hypomagnesaemia by cyclosporin. PMID- 2212081 TI - Parathyroid hormone related peptide in ovarian carcinoma. PMID- 2212082 TI - Prorenin in ovarian cyst fluid. PMID- 2212083 TI - Plaque and chronic inflammatory periodontal disease. A question of ecology. AB - The nature of the relationship between dental plaque and chronic inflammatory periodontal disease (CIPD) remains unclear, although there is no doubt that plaque is the direct cause. Non-specific, specific and exogenous hypotheses have been proposed to explain plaque-host relationships. Current evidence indicates that plaque is part of the natural human microflora, one of many such in nature, and that disruption of oral microbial ecology, due primarily to diet texture changes, leads to gingivitis and periodontitis. These result in increased plaque accumulation, and particularly in increased interdental effective plaque thickness. The latter leads to alterations in plaque ecology, particularly increasing anaerobiosis, with resultant shifts in proportions of its constituent species. These shifts are responsible for the increased counts of, for example, Bacteroides gingivalis, Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Wolinella recta, spirochaetes and others, associated with chronic periodontitis in its various forms. Measures to prevent or control chronic periodontitis should aim, not to eliminate plaque, which ignores ecology and would compromise host defence, but to restore the species distribution in plaque to that compatible with health. PMID- 2212084 TI - Morphological compositions of subgingival microbiota in Actinobacillus actinomycetemcomitans-associated periodontitis. AB - Infrequent occurrence of spirochetes and rather low proportions of these organisms have been reported in localized juvenile periodontitis, where periodontal lesions often harbour large numbers of Actinobacillus actinomycetemcomitans, a suspected principal periopathogen strongly implicated in the pathogenesis of this and other forms of chronic periodontitis. We studied the association of subgingival A. actinomycetemcomitans with the morphological composition of the subgingival microbiota in a large population of patients suffering from advanced periodontitis. Subgingival plaque from the deepest pockets of every quadrant of their dentitions was sampled and pooled in 70 patients between 14 and 63 years of age, and analysed morphologically by phase contrast microscopy. A minimum % similarity index was employed to define 4 clusters with different morphological composition of the floras. The actual proportion of A. actinomycetemcomitans was determined at 2 sites with deep periodontal pockets. All clusters harboured patients infected with A. actinomycetemcomitans. If present, in clusters predominated by motile rods or medium-sized spirochetes, the organism was found in rather low proportions (median 5.3% and 3.4%, respectively). However, the cluster with a pooled flora mainly consisting of coccoid cells revealed periodontal sites with A. actinomycetemcomitans in proportions of more than 53% (median), if the organism was present (p less than 0.01). We found a positive correlation between proportions of A. actinomycetemcomitans and cocci (R = 0.65) and negative correlations with spirochetes and motile rods (R = 0.61, R = -0.59, respectively). Cautious interpretation of subgingival plaque predominated by coccoid cells is recommended, if deep periodontal pockets and obvious signs of inflammation are present, since these pockets were found to be often infected with large numbers of A. actinomycetemcomitans. PMID- 2212085 TI - Temperature as a periodontal diagnostic. AB - Elevated temperature, normally a characteristic of inflammation, is a potential indicator of periodontal disease. Conversely, local periodontal site temperatures within normal variation could suggest relative periodontal health. To evaluate this potential, a temperature probe was designed with rapid response (less than 1 s), high accuracy and reproducibility (+/- 0.1 degree C), good transducer thermal isolation and physical dimensions approximating those of a conventional periodontal probe. To compensate for subject-to-subject variations in core temperature, site temperatures were measured and expressed as differences relative to the sublingual temperature. A cross sectional study was conducted using this instrument in which pocket temperatures of 14 subjects with advanced adult periodontitis were measured and compared with the sulcus temperatures of 11 healthy subjects. Overall, the mean site temperature of the diseased subjects was 0.65 degree C higher than that of the healthy subjects. A natural posterior-to anterior temperature gradient was observed with the posterior sites being hotter than the anterior sites. Tooth-by-tooth analysis showed that diseased teeth have higher temperatures than anatomically equivalent healthy teeth (p less than 0.01). Threshold temperatures for differentiating diseased and healthy teeth were determined to optimize sensitivity and specificity. The results suggest that site temperature is a diagnostic of inflammatory activity associated with periodontal disease. The specifically designed instrument detected significant disease related departures from normality. PMID- 2212086 TI - Reliability of attachment loss measurements in a longitudinal clinical trial. AB - In order to appropriately carry out a longitudinal assessment of periodontal attachment loss in individuals with untreated periodontitis, reliable criteria for determining "real" changes in attachment level (AL) are required. In the present study, 25 subjects were to be examined every 2 months for up to 2 years to determine changes in AL and to relate clinical and laboratory criteria to such changes. Trained examiners for the study underwent calibration trials to determine inter-examiner and intra-examiner reliability both before the study and at intervals during the study. It was found that AL measurements were in agreement within 2 mm more than 95% of the time. The calibration trials provided an estimate of the error in attachment loss measurements, since no "real" attachment loss had occurred. From estimates of measurement error, the probability of false positive changes were determined. It was found that acceptable false positive rates (less than 5%) could be achieved if 2 examiners each detected 3 mm change at a given site or if 2 examiners each detected 2 mm change at a site and verified that this change persisted at a subsequent examination. The results of the longitudinal trial were then compared to the probability estimates calculated from the calibration trials. It was found that probabilities of AL changes detected during the longitudinal trial for less stringent conditions than described above (e.g., single examiner, 2 examiners unconfirmed) were similar to to previously estimated false positive rates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212088 TI - Comparative effects of 2 chemotherapeutic mouthrinses on the development of supragingival dental plaque and gingivitis. AB - A 6-month double-blind, controlled clinical study was completed with 124 healthy adult subjects to determine the efficacy of 2 mouthrinses, Listerine (LA) and Peridex (PX), used as supplements to regular oral hygiene measures in reducing supragingival dental plaque and gingivitis. Following screening examinations for entry levels of existing gingivitis and plaque, baseline gingival and plaque area indices, extrinsic tooth stain, supragingival calculus, bleeding and soft tissue condition were recorded. All subjects then received a complete dental prophylaxis to remove plaque, calculus and extrinsic stain. Subjects were randomly assigned to 1 of 3 groups and performed supervised rinses twice daily for 30 s in addition to their normal oral hygiene, for 6 months. All indices were again evaluated at 3 and 6 months. After 6 months, LA and PX significantly (p less than 0.001) inhibited development of plaque by 36.1% and 50.3%, respectively, and the development of gingivitis by 35.9% and 30.5%, respectively, compared to a hydroalcohol control. PX was more effective in inhibiting plaque and both mouthrinses appeared to be equally effective in inhibiting gingivitis. LA patients did not develop significant levels of stain or supragingival calculus at 6 months, compared to baseline or control. PX patients developed significant levels of extrinsic stain and supragingival calculus compared to baseline and control. Though PX was more effective than LA in the control of plaque, this study indicates that both LA and PX were effective agents in a regimen for the control of plaque and gingivitis. PMID- 2212087 TI - Microbiological and clinical effects of a dentifrice containing zinc citrate and Triclosan in the human experimental gingivitis model. AB - A partial mouth experimental gingivitis model was employed to establish the effect of a dentifrice containing 0.2% Triclosan and 0.5% zinc citrate on the development of chronic gingivitis. In addition, changes in the plaque flora associated with the developing gingivitis have been monitored. Following a period of stringent oral hygiene, volunteers were allocated to 1 of 2 treatment groups. A toothshield was constructed to fit 4 posterior mandibular teeth. During the 21 day experimental period test or placebo dentifrice was applied to the experimental teeth via the tooth shield. The toothshield also prevented plaque removal from those teeth during habitual brushing of the remaining dentition. Supragingival plaque was collected at baseline and day 21 for analysis of the total bacterial flora. At the end of the experimental period, plaque and gingivitis had developed in both groups. However, the test group had significantly less plaque and gingivitis than the placebo group. The microbiological data demonstrated that plaque from the test group contained significantly lower numbers of anaerobes compared to plaque from the placebo group. This was considered particularly significant as these bacteria are generally associated with chronic inflammatory periodontal disease. There was also a trend for the numbers of actinomyces to decrease in plaque from the test group but not in the placebo group. PMID- 2212089 TI - Subjective criteria and probing attachment loss to evaluate the effects of plaque control and root debridement. AB - 11 adult patients with moderate to advanced periodontitis were treated with oral hygiene instruction and an initial, single episode of root debridement. Before therapy, 3 independent clinicians examined all patients and identified sites that in their opinion probably would not respond to the therapy and would continue to lose attachment. On 2 occasions, 3 and 12 months later, the clinicians re examined and re-evaluated all patients and all sites. The results of therapy were also monitored by probing attachment level measurements performed every 3rd month. All 11 patients completed 24 months of follow-up, and 6 subjects were available until 36 months. Sites with probing attachment loss after 12, 24 and 36 months were identified using linear regression analysis and compared to the clinicians' prediction of probing attachment loss. The results demonstrated a limited agreement between probing attachment loss determined by linear regression and the clinicians' predictions of probing attachment loss. It appears that the traditional clinical signs and factors used to forecast and identify periodontal disease activity are only moderately associated with probing attachment loss. This suggests that attachment loss may be caused by several factors, at least following initial therapy. The progression of an inflammatory disease of microbial etiology may be only 1 of such causes. Further studies are needed to clarify the nature and cause of probing attachment loss. PMID- 2212092 TI - Decriminalizing drug use. PMID- 2212090 TI - Irrigation with chlorhexidine to resolve naturally occurring gingivitis. A methodologic study. AB - This study compared oral irrigation and rinsing with chlorhexidine (CHX) and placebo in the treatment of naturally occurring chronic gingivitis. 44 subjects with at least 6 interproximal sites which bled on probing were randomly distributed on a double-blind basis into 4 treatment groups, placebo-rinse, CHX rinse (0.12%), placebo-irrigation and CHX-irrigation (0.06%). A half-mouth was scaled 2 weeks prior to therapy in all groups. Rinses were performed 2 times daily and irrigation was performed once a day by means of an oral irrigator with the tip directed at a right angle to the tooth. Subjects continued with routine oral hygiene without instruction. The active treatment period was 2 months. Parameters were recorded at baseline and at 60 days. At the conclusion, marginal plaque was cultured for predominant microbial types. CHX-rinse (0.12%) and CHX irrigation (0.06%) significantly reduced (p less than 0.05) plaque. Gingival bleeding decreased by 26% in both scaled and unscaled sites following CHX (0.12%) rinses and by 40% at both types of sites following CHX (0.06%) irrigation. Bleeding was reduced with CHX-irrigation greater (p less than 0.05) than with the placebo-irrigation. The mean log of colony-forming units of Actinomyces species was significantly lower (p less than 0.05) in the CHX (0.12%) rinse and CHX (0.06%) irrigator groups than in the placebo groups. These data therefore indicate that delivery of CHX (0.06%) by an oral irrigator is an effective means of treating naturally occurring gingivitis. PMID- 2212091 TI - Controlled force measurements of gingival attachment level made with the Toronto automated probe using electronic guidance. AB - Precise reproduction of probe placement, probing force and probing angulation may influence the reliability of replicate gingival attachment level measurements (GAL). Reproducibility of GAL measurements was determined with the Toronto automated periodontal probe (TAPP) in which a novel electronic guidance system was incorporated to improve the precision of probing angulation. Bench testing of forces produced at the probe tip was performed with an electronic balance. Reproducibility and precision of force generation were tested in a variety of instrument configurations using laboratory models. The data indicated that highly precise and reproducible probing forces can be generated with the TAPP over a large (10 to 90 g) probing range. Instrument precision was +/- 0.27 mm when probing forces of 40-60 g were used. The guidance system provided accurate and reproducible measurements of the probe handle in both roll and pitch axes when compared with precisely machined wedges (R = 0.99, roll; R = 0.98, pitch). Deviation of probing angulation greater than 5 degrees on replicate measurements of GAL was associated with significant alterations in the location of circumferential probe placement and in the size of the difference between GAL measurements (delta GAL). Clinical assessment of probing angulation in 6 patients demonstrated that delta GAL was 0.40 +/- 0.05 mm when probing angulation deviation was less than 5 degrees but increased to 0.96 +/- 0.11 mm when deviations exceeded 5 degrees. Taken together, these data indicate that the regulation of probing angulation in clinical measurement of GAL with the TAPP is an important determinant of the reproducibility of periodontal probing. PMID- 2212093 TI - Survey of cardiac rehabilitation centers in New York City. AB - Out-patient cardiac rehabilitation centers in New York City were surveyed in order to determine current practices. All 24 centers operating as of May, 1987 were sent questionnaires; 16 responded for a return rate of 67 percent. In general, practices of the centers were in accord with guidelines of the American Heart Association (AHA) and the American College of Sports Medicine. The incidence of medical complications in the centers was quite rare, perhaps accounting for the failure of centers to follow all emergency guidelines of the AHA, such as daily testing of the defibrillator. The major aim of the centers was to enhance physiological status, rather narrowly defined as aerobic fitness and cardiovascular function. Little attention was paid to nutrition, body composition and strength, despite the fact that the value of broadening the concept of fitness to include these parameters is becoming evident. Lifestyle counseling to help in long-term rehabilitation was also rare. Third party payers should be encouraged to support such components of a rehabilitation program so that centers would be more likely to incorporate them. PMID- 2212094 TI - Prevalence of alcohol consumption among older persons. AB - Percent prevalences of alcohol consumption were determined in a cross-sectional study of randomly chosen residents of San Diego County, California aged 45 years and over. The study sample (N = 2,105) showed statistically significant drinking differences between Whites (n = 819), Blacks (n = 629), and Mexican-Americans (n = 657). Overall, the highest prevalence of drinking occurred among the White elderly. The common belief that socioeconomic conditions are inversely associated with a high prevalence of drinking was not supported in this sample. Statistically significant differences in age-specific and sex-specific percent prevalences of alcohol intake were also found. There was a generally decreasing prevalence of alcohol consumption with advancing age, which existed regardless of ethnicity. Initial empirical measures and a better understanding of drinking correlates will identify those elderly persons at risk and provide the basis for future interventions in the areas of applied epidemiology and health promotion. PMID- 2212095 TI - Pre-diagnostic symptom recognition and help seeking among cancer patients. AB - Failure to recognize symptoms which signal cancer may delay contact with the medical care system, thus decreasing the chances of diagnosis at an early stage of disease. We investigated the determinants of cancer symptom recognition and delay in seeking medical care in a population-based sample of 625 newly diagnosed lung, breast and colorectal cancer patients. Although the majority (79.5%) of patients reported noticing symptoms prior to diagnosis, one quarter of these patients (24.7%) delayed longer than three months in seeking medical care. Contrary to the findings of research based on clinic samples, logistic regression analysis revealed that no demographic or social support factors were predictive of symptom recognition or delay, with the exception that older colorectal cancer patients were less likely to notice symptoms, but also less likely to delay. Lung and colorectal patients diagnosed with advanced disease were more likely to notice symptoms than patients with local disease. Results of a content analysis of patients' remarks indicate that breast cancer patients were significantly more likely than lung or colorectal cancer patients to attribute their symptoms to cancer (p less than .001). Symptoms common to lung and colorectal cancer appear to be attributed to other, less serious causes. Given the lack of demographic predictors of symptom recognition and delay in seeking care, we suggest that education programs address risk groups for specific cancers, rather than the general public as a whole, grouping together all cancers and cancer symptomatology. PMID- 2212096 TI - Community health in a rural area of Sudan. AB - A community survey was conducted in Al awayda village, one of eight villages selected for study in the rural Gezira province of Sudan. The objective of the survey was to identify the main health, social and economic problems of people in rural areas and to set priorities as a first phase in a rural development program. The results showed a high illiteracy rate and poor socioeconomic status aggravated by the drought and famine which affected this area of Africa in the years 1983-85. There was an inadequate safe water supply, poor environmental sanitation and inadequate primary health care services. The major disease problems were malaria, diarrheal diseases and schistosomiasis. The implementation of primary health care services with special emphasis on maternal and child health and health education is a clear need. The impact of Sennar Sugar Agricultural Scheme on this village is also discussed. PMID- 2212097 TI - Children of homeless families: health status and access to health care. AB - The parents and children of homeless families are highly vulnerable to illness and the failure to receive timely and continuous health care. Data on health status and health care utilization were collected from 70 homeless families selected for an intensive case management program and compared to data for low income families. The data suggest that homeless children do not utilize primary care or preventive care on a regular basis in comparison to low income children generally. These results have implications for the delivery of health care services to homeless families in shelters. PMID- 2212098 TI - Requirement for olfactory axons in the induction and stabilization of olfactory glomeruli in an insect. AB - The role of antennal sensory axons in the induction and stabilization of olfactory glomeruli has been explored in the moth Manduca sexta. First, we asked the question: how many axons are necessary to induce glomerulus formation within the first-order olfactory neuropil of the brain? Axons from as few as 10 of the normal 70-80 repeating antennal segments were sufficient to induce glomeruli. However, there was a dose dependence in the number of glomeruli that developed in partially innervated lobes. When only 11 segments of the antenna were allowed to provide innervation to the lobe, only 37 of the normal 59 +/- 2 glomeruli developed; over 20 segments were necessary to induce the normal number of glomeruli. In a second set of experiments, we asked: for how long must antennal axons be present to stabilize newly formed glomeruli? We found that antennal axons must be intact for at least 2 to 4 stages (roughly equivalent to 2 to 4 days) for glomeruli to be stable even if the axons are subsequently severed. This finding, taken in the light of other recent findings in our laboratory, suggests that the formation of synapses may be a crucial element in the stabilization of glomerular structure. All together, the results of the present study indicate that induction and stabilization of glomeruli are separable events with different underlying cellular bases. PMID- 2212099 TI - Comparative study of histamine immunoreactivity in nervous systems of Aplysia and Pleurobranchaea. AB - The distribution of histamine in the nervous system of the marine molluscs Aplysia californica and Pleurobranchaea californica was studied by using a newly available immunohistochemical localization technique and specific antiserum against histamine-protein conjugate. We examined several sets of complete histological sections through the major ganglia of both animals, as well as all nerve roots of the buccal and cerebral ganglia and the corresponding target tissues. The results indicate that histamine is present in several neurons and/or nerve fibers of all major ganglia. An especially dense histamine fiber network in the buccal ganglion of both species suggests a major role for histamine in regulation of buccal-oral behaviors. Histamine was also observed in several identified nerve roots of the buccal and cerebral ganglia, as well as in the corresponding target tissues. Its localization in the Aplysia radular sac and in the statocyst neurons of both species suggest a role for histamine in sensory functions. Our study revealed many previously unknown histamine cells or cell clusters, some of which may be identifiable by electrophysiological methods. The findings also point to possible reinterpretation of previous findings, indicating that histamine may be a cotransmitter in identified cells, whereas the methodology itself suggests that special precautions must be taken to avoid spurious interpretations of specificity. As has now been observed in studies of serotonergic immunohistochemistry and in our own findings on VIP, histamine terminals were observed to lie in close contact with somata and axon hillocks, all of which suggest that axo-somatic connections in molluscs may be more prevalent than previously considered. PMID- 2212100 TI - Demonstration of discrete place-defined columns--segregates--in the cat SI. AB - The SI forelimb area of cats was examined with receptive field (RF) mapping techniques. Arrays of closely spaced, near-radial microelectrode penetrations were inserted into the crown of postsigmoid gyrus of ketamine anesthetized subjects and minimal RFs were obtained at several depths. The minimal RF was defined as the skin site providing the strongest input to each recorded cluster of neurons. Data analysis showed that all studied cortical territories contained groups of discrete cortical columns, 300-400 microns in diameter. The columns were regarded as topographic entities because no change in minimal RF location could be observed within their boundaries. The boundaries of columns were sharp and could be unequivocally distinguished because the minimal RFs sampled on opposite sides of a boundary occupied displaced, nonoverlapping positions. Pair wise comparison of single neuron maximal RFs (defined as the entire skin area providing input to the recorded neuron) further clarified the nature of the SI place-defined columns: (1) no systematic differences in maximal RF position could be demonstrated for different parts of the same column (even though the maximal RFs in most columns varied extensively in size and skin areas covered), and (2) at the boundary between neighboring columns maximal RFs shifted en masse to center on a new skin locus. These minimal and maximal RF observations strongly support our recent proposal that body surface is represented in SI by a honeycomblike mosaic of discrete place-defined cortical columns, segregates. PMID- 2212101 TI - Vasopressinergic innervation of the mouse suprachiasmatic nucleus: an immuno electron microscopic analysis. AB - Attempts are being made to unravel the local circuitry of the suprachiasmatic nucleus, with a view toward eventually correlating specific neuronal systems with circadian events. Hence, the vasopressinergic innervation of this nucleus in the laboratory mouse has been analyzed immunocytochemically at the light and electron microscopical levels. Monoclonal antineurophysin and polyclonal antivasopressin were used on aldehyde-fixed brains. Serial vibratome sections of the appropriate forebrain region were prepared for pre-embedding immunoperoxidase staining and/or postembedding immunogold labeling. Immunoreactive somata, processes, varicosities, and synaptic terminals were found throughout the suprachiasmatic nucleus, their ratio and density varying at different locations. The predominant type of vasopressinergic soma was ovoid to rounded (7-10 microns), containing secretory granules (85-120 nm), a large proportion of which were immunoreactive. Axon terminals, both nonimmunoreactive and immunoreactive, impinged upon vasopressinergic somata and processes, often displaying synaptic specializations. Vasopressinergic terminals, containing secretory granules and microvesicles, were found throughout the nucleus, particularly within the dorsomedial neuropil. These labeled terminals varied in size (0.4-3.4 microns 2) and shape, ranging from compact boutons to pleomorphic profiles, some deeply indented by postsynaptic spines, either dendritic or somatic. Approximately 65% of the vasopressin containing terminals were axodendritic and 30% axosomatic; about 5% appeared to be axoaxonic. At least a quarter of all vasopressinergic synaptic terminals were axospinous. Other forms of interneuronal contact involving vasopressinergic elements (somata, dendrites) included extensive membrane to membrane appositional sites, and multiple puncta adhaerentia. The versatility of interconnections between vasopressin-containing neurons in the mouse suprachiasmatic nucleus suggests a highly active and coordinated network, which contributes substantially to local intranuclear circuitry. In addition, a dense efferent vasopressinergic output is directed dorsally towards the periventricular hypothalamus, where direct associations may be established with diverse hypothalamic neuroendocrine systems. PMID- 2212104 TI - The projection from different visual cortical areas to the rat superior colliculus. AB - The rat occipital cortex contains a number of morphologically and physiologically distinct visual areas. Retrograde tracing studies have shown that most if not all of these areas project in a topographic fashion to the ipsilateral superior colliculus (SC). In the present study, small amounts of wheat germ agglutinin conjugated HRP (WGA-HRP) were injected into adult rat occipital cortex to determine how afferents from the different visual cortical areas are distributed within the various layers of the SC. Cytoarchitectonic criteria were used to help establish the location of the WGA-HRP injections in the cortex. As a further aid to identifying the sites of injection, the distribution of retrogradely labelled cells within the thalamus was mapped in each brain. Analysis revealed a surprising range of visuocortical projections to the rat SC, with input to the majority of tectal laminae. Area 17 projected most heavily to the dorsal stratum opticum (SO) and lower half of stratum griseum superficiale (SGS) with lighter label extending up to the collicular surface. Axons and terminals from area 18 formed two horizontal tiers, one in the middle of the stratum griseum intermediale (SGI) and the other at the border between the stratum album intermediale (SAI) and the stratum griseum profundum (SGP). Periodic puffs of label extended between these horizontal tiers, with a periodicity of 300-400 microns. There was some variability in the labelling pattern in the superior colliculus after area 18a injections, perhaps because this cytoarchitectonic area contains multiple representations of the visual field. Generally the projection from the lateromedial, laterointermediate, and laterolateral parts of 18a was heaviest in the lower half of SO and upper regions of SGI. Lighter label extended up into the lower half of SGS. In the SGI it was common to find periodic puffs of terminal label interspersed with areas devoid of innervation. This periodic pattern was particularly noticeable after WGA-HRP injections into anterior 18a. Two horizontal tiers of label were located at the SO/SGI border and SGI/SAI border (the dorsal being the most dense) with patches of label extending between these tiers every 230-250 microns. There did not appear to be a significant corticotectal projection from the posterior part of the lateral extrastriate region. PMID- 2212103 TI - Light and electron microscopical studies on the spherical neurons in the electrosensory lateral line lobe of the gymnotiform fish, Sternopygus. AB - Spherical cells are a principal cell type of the electrosensory lateral line lobe (ELLL) and play a crucial role in the jamming avoidance response (JAR) behavior. Since Sternopygus, a low frequency gymnotiform genus, does not display a JAR we searched for spherical cells in its ELLL. While present in Sternopygus, spherical cells differed remarkedly from those in the high-frequency gymnotiforms, Eigenmannia and Apteronotus. This study reveals species-characteristic differences in the morphology and synaptology of the spherical cell, a projection neuron located in the deep neuropil layer (DNL) of the ELLL. In contrast to the adendritic spherical cell of other species, the spherical neuron in Sternopygus exhibits an extensive basilar dendrite that extends into the primary electroreceptive afferent zone, the deep fiber layer (DFL). In Sternopygus, these neurons are distributed evenly across the full length of each tuberous subdivision, with cell densities highest in the centrolateral subdivision. At the ultrastructural level, the contacts on the soma, proximal, and distal dendrite of the spherical neuron in Sternopygus are asymmetrical chemical synapses, quite distinct from the electrotonic gap junctions found on the spherical neurons of other species. PMID- 2212102 TI - Occipital cortex in man: organization of callosal connections, related myelo- and cytoarchitecture, and putative boundaries of functional visual areas. AB - Human area 17 is known to contain a single (the primary) visual area, whereas areas 18 and 19 are believed to contain multiple visual areas (defined as individual representations of the contralateral visual hemifield). This is known to be the case in monkeys, where several boundaries between visual areas are characterized by bands of callosal afferents and/or by changes in myeloarchitecture. We here describe the pattern of callosal afferents in (human) areas 17, 18, and 19 as well as their cortical architecture and we infer the position of some visual areas. Sections from occipital lobes of 6 human brains with unilateral occipital infarctions have been silver-impregnated for degenerating axons, thereby revealing callosal afferents to the intact occipital cortex. Their tangential distribution is discontinuous, even in cases with large lesions. A band of callosal afferents straddles the area 17/18 boundary, whereas the remainder of area 17 and a 15-45 mm wide stripe of area 18 adjacent to the callosal band along the 17/18 border are free of them. Patches of callosal afferents alternate with callosal-free regions more laterally in area 18 and in area 19. We conclude that, in man, a second visual area (analogue of V2) lies in area 18, horseshoe-shaped around area 17, and includes the inner part of the acallosal stripe adjacent to the callosal band along the 17/18 boundary. The outer part of this acallosal stripe belongs to a third visual area, which may contain dorsally the analogue of V3 and ventrally that of VP. Thus the lower parts of the second and third visual areas lie on the lingual gyrus, whereas the analogue of the macaque's fourth visual area probably lies on the fusiform gyrus. Although the proposed subdivision of the occipital cortex relies largely on the pattern of callosal afferents, some putative human visual areas appear to have distinct architectonic features. The analogue of V2 is rather heavily myelinated and its layer III contains large pyramidal neurons. Its upper part is not well delimited laterally since adjacent "V" has similar architecture. Its lower part, however, differs clearly from the adjacent "VP," which is lightly myelinated and lacks the large pyramids in layer III. The cortex lateral to "VP" is heavily myelinated and contains fairly large pyramids in layers III and V. The myeloarchitecture of the lateral part of the occipital cortex is not uniform; a very heavily myelinated region stands out in the lateral part of area 19, near the occipito-temporal junction.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2212105 TI - Growth of injured rabbit optic axons within their degenerating optic nerve. AB - Spontaneous growth of axons after injury is extremely limited in the mammalian central nervous system (CNS). It is now clear, however, that injured CNS axons can be induced to elongate when provided with a suitable environment. Thus injured CNS axons can elongate, but they do not do so unless their environment is altered. We now show apparent regenerative growth of injured optic axons. This growth is achieved in the adult rabbit optic nerve by the use of a combined treatment consisting of: (1) supplying soluble substances originating from growing axons to be injured rabbit optic nerves (Schwartz et al., Science, 228:600-603, 1985), and (2) application of low energy He-Ne laser irradiation, which appears to delay degenerative changes in the injured axons (Schwartz et al., Lasers Surg. Med., 7:51-55, 1985; Assia et al., Brain Res., 476:205-212, 1988). Two to 8 weeks after this treatment, unmyelinated and thinly myelinated axons are found at the lesion site and distal to it. Morphological and immunocytochemical evidence indicate that these thinly myelinated and unmyelinated axons are growing in close association with glial cells. Only these axons are identified as being growing axons. These newly growing axons transverse the site of injury and extend into the distal stump of the nerve, which contains degenerating axons. Axons of this type could be detected distal to the lesion only in nerves subjected to the combined treatment. No unmyelinated or thinly myelinated axons in association with glial cells were seen at 6 or 8 weeks postoperatively in nerves that were not treated, or in nerves in which the two stumps were completely disconnected. Two millimeters distal to the site of injury, the growing axons are confined to a compartment comprising 5%-30% of the cross section of the nerve. A temporal analysis indicates that axons have grown as far as 6 mm distal to the site of injury, by 8 weeks postoperatively. Anterograde labeling with horseradish peroxidase, injected intraocularly, indicates that some of these newly growing axons arise from retinal ganglion cells. PMID- 2212106 TI - Cerebellar nucleo-olivary projections in the rat: an anterograde tracing study with Phaseolus vulgaris-leucoagglutinin (PHA-L). AB - In order to evaluate the reciprocity of olivo-cerebellar and cerebello-olivary connections, a detailed description of the cerebellar nucleo-olivary projection in the rat is presented using small, iontophoretic injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin. Sparse projections were found to arise from the rostral part of the medial cerebellar nucleus toward the lateral part of the caudal medial accessory olive. Its medial parts receive a projection from the dorsolateral protuberance of the medial cerebellar nucleus. Caudal and lateral regions of the medial cerebellar nucleus project to the "beta" group and dorsomedial cell column. Heavy olivary projections to circumscribed parts of the inferior olive were found after injections in the remaining cerebellar nuclei. The medial part of the posterior interposed nucleus connects to caudolateral areas of the rostral half of the medial accessory olive, whereas lateral areas project to more rostromedial parts. The most ventromedial part of the lateral cerebellar nucleus projects to the ventrolateral outgrowth. Adjacent medial, ventral, and caudal regions connect to the ventral leaf of the principal olive. The cerebellar origin of the projection to its dorsal leaf is located in lateral, dorsal, and rostral parts of the lateral cerebellar nucleus. The dorsolateral hump projects to the dorsomedial group of the rat inferior olive. Rostromedial projections to the dorsal accessory olive originate from the lateral part of the anterior interposed nucleus, whereas its medial parts project to more lateral and caudal regions of this olivary subnucleus. The dorsal fold of the dorsal accessory olive does not receive a projection from the cerebellar nuclei but from the lateral vestibular nucleus. No cerebellar projections were found to the dorsal cap. Relatively strong ipsilateral projections, which were the mirror images of the contralateral projections, were observed in the dorsomedial group, rostral medial accessory olive, and ventral leaf of the principal olive. When both the inferior olive and the cerebellar nuclei are considered as folded but continuous sheets of grey matter, the complete nucleo-olivary projection can be described as a simple transformation. PMID- 2212107 TI - Morphology of sympathetic preganglionic neurons in the neonatal rat spinal cord: an intracellular horseradish peroxidase study. AB - Understanding the central neural control of autonomic functions requires a knowledge of the morphology of the preganglionic neurons, for the location of the dendritic arborizations of these neurons will indicate which central pathways may have access to them. In the present study, individual sympathetic preganglionic neurons in the neonatal rat spinal cord have been examined by the intracellular injection of horseradish peroxidase (HRP) in an in vitro preparation. Seventeen HRP-labeled preganglionic neurons in thoracic segments T1-T3 were examined in detail; of these, 12 somata were located in the intermediolateral cell column (IML), one in the lateral funiculus (LF), two in the intercalated nucleus (IC), and two at the border between IML and IC. All of the neurons had extensive dendritic arborizations arising from an average of six primary dendrites; the average total dendritic length for these cells was 2,343 microns. The morphology of preganglionic neurons differed depending on the location of their cell bodies. Preganglionic neurons located in the IML were essentially two-dimensional: the cells had some dendrites that coursed rostrocaudally for 300-500 microns within the IML and others that coursed mediolaterally, extending to the lateral surface of the cord and close to the central canal. Axons of these cells coursed ventrally from the cell body and exited from the spinal cord at the first ventral root caudal to the cell body. No intraspinal axon branches were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212108 TI - Localization and characterization of neuropeptide Y in the brain of Microcebus murinus (Primate, Lemurian). AB - The distribution of neuropeptide Y (NPY) in the brain of the lemur Microcebus murinus was determined by immunocytochemistry with the aid of a highly specific antiserum against synthetic porcine NPY. When compared with previous immunohistochemical data obtained in primates and other mammalian species, the localization of NPY-immunoreactive (IR) structures in the Microcebus murinus brain revealed particular features. (1) Numerous NPY-IR perikarya and a dense network of IR nerve terminals were found in the supraoptic and suprachiasmatic nuclei, respectively. The occurrence of NPY-IR perikarya in the supraoptic nucleus, also reported in the squirrel monkey, seems to be specific to primates. In the squirrel monkey, the suprachiasmatic nucleus exhibits only a moderate innervation, whereas in humans it appears totally devoid of NPY-IR fibers. (2) IR perikarya and axon processes were observed in many upper brainstem areas, in particular in the interpeduncular, raphe pontine, dorsal tegmental, parabrachial, and dorsal raphe nuclei, in the locus coeruleus, the nucleus of the solitary tract, and the reticular formation; in this latter area, the occurrence of two categories of NPY-IR neurons was demonstrated on the basis of their morphology and localization, suggesting that they may play distinct roles. (3) NPY-IR nerve processes could be traced over a long distance. (4) For the first time, numerous NPY-IR terminals were observed close to the lumen of the various cerebral ventricles. The immunoreactive NPY-like peptide was characterized by combining high performance liquid chromatography (HPLC) analysis and radioimmunoassay quantification. The dilution curves obtained with synthetic porcine NPY and serial dilutions of occipital cortex, paraventricular and supraoptic hypothalamus, posterior hypothalamus, medulla oblongata, or preoptic area extracts were parallel. The highest amounts of NPY were measured in the hypothalamus and telencephalon. HPLC analysis resolved a single peak of NPY-like immunoreactivity that exhibited the same retention time as synthetic porcine NPY. The distribution of NPY in the lemurian brain is discussed with respect to phylogeny and putative functions. PMID- 2212109 TI - Distribution of septohippocampal neurons containing parvalbumin or choline acetyltransferase in the rat brain. AB - A combination of retrograde transport of horseradish peroxidase or wheat germ agglutinin-colloidal gold with either single or double-label immunohistochemistry is used to describe the comparative topographic distribution of parvalbumin- and choline acetyltransferase-immunoreactive septal neurons that project to the hippocampal formation of the rat. The morphometric parameters of the retrogradely labelled, parvalbumin-containing neurons were very similar, if not identical, to those neurons of the midline and medial part of the medial septum and the diagonal band regions that had previously been shown to be immunoreactive for gamma-aminobutyric acid or for glutamate decarboxylase following colchicine treatment. The total number of parvalbumin-immunoreactive and choline acetyltransferase-positive retrogradely labelled cells was counted at 9 representative levels through the rostrocaudal extension (from 2.4 mm anterior to the level of bregma) of the medial septal-diagonal band complex. In the whole medial septum-vertical limb of the diagonal band region, about 33% of the total retrogradely labelled neurons showed immunoreactivity to parvalbumin, whereas the parvalbumin-negative cells were mainly choline acetyltransferase-immunopositive. In comparison with the average figure, the proportion of the retrogradely labelled parvalbumin-containing neurons was higher in the middle part (around 1.5 mm anterior to the bregma) than in either the rostral or caudal ends. The reverse was true for the distribution of the cholinergic septohippocampal neurons. At the maximum levels the parvalbumin-immunoreactive neurons accounted for more than half of the total retrogradely labelled cells in 4 out of 6 rats. Moreover, within the complexity of the septal neurons, a marked regularity of topographic organisation was observed in the distribution of retrogradely labelled parvalbumin-containing GABAergic and choline acetyltransferase-positive cholinergic neurons as if they were subdivided cytoarchitectonically. PMID- 2212110 TI - Distribution and brainstem origin of cholecystokinin-like immunoreactivity in the opossum cerebellum. AB - In order to determine the distribution of the peptide cholecystokinin (CCK) within the cerebellum and medullary precerebellar nuclei of the adult opossum, sections of these brain regions were processed for peroxidase-antiperoxidase immunohistochemistry. Within the inferior and superior cerebellar peduncles, fine beaded fibers are evident and a beaded plexus of fibers is present in all the cerebellar nuclei. In the overlying cerebellar cortex, CCK-positive mossy fiber rosettes are present in all lobules, where their morphology varies from simple enlargements to more complex rosettes. However, their distribution varies particularly in vermal lobules II, III, VII, and IX where they are organized in parasagittal bands. Climbing fibers that are positive for CCK are present in very restricted areas of vermal lobules IV, VII, and VIII. After colchicine pretreatment, CCK-positive cell bodies are seen in restricted regions of the posterior interposed and fastigial nuclei as well as within several precerebellar nuclei known to give rise to mossy fibers. Such nuclei include the lateral cuneate nucleus, the nucleus prepositis hypoglossi, the nucleus reticularis lateralis, the nucleus raphe obscurus, the paramedian reticular nucleus, the nucleus reticularis gigantocellularis, and the medial vestibular nucleus. To localize the brainstem origin(s) of the CCK fibers in the cerebellum, a double label paradigm employing a retrograde tracer and CCK immunohistochemistry was used. These experiments indicate that CCK mossy fibers originate primarily within the lateral cuneate nucleus, the perihypoglossal complex, and the lateral reticular nucleus. Some also originate within the medial vestibular nucleus and the nucleus reticularis gigantocellularis. In addition, double-labeled cell bodies are present within the caudal medial accessory inferior olive, the likely source of the CCK-positive climbing fibers. These data indicate that specific populations of climbing fibers and mossy fibers may utilize CCK to alter the firing rate of their target neurons. PMID- 2212111 TI - Immunohistochemical study of the serotoninergic innervation of the basal ganglia in the squirrel monkey. AB - A specific antibody raised against 5-hydroxytryptamine (5-HT) conjugated to bovine serum albumin was used to study the serotoninergic innervation of the basal ganglia in the squirrel monkey (Saimiri sciureus). At midbrain level, numerous fine 5-HT-immunoreactive axons were seen to arise from the immunopositive neurons of the dorsal raphe nucleus and less abundantly from those of the nucleus centralis superior. The bulk of these axons formed a rather loosely arranged bundle that arched ventrorostrally through the central portion of the midbrain tegmentum and ascended toward the ventral tegmental area. Several fascicles detached themselves from this bundle to reach the substantia nigra where they arborized into a multitude of heterogeneously distributed 5-HT terminals. The 5-HT innervation was particularly dense in the pars reticulata but much less so in the pars compacta of the substantia nigra. More rostrally other 5 HT fibers swept dorsolaterally and formed a remarkably dense network of varicose fibers within the subthalamic nucleus. A multitude of 5-HT axons continued their ascending course within the lateral hypothalamic area, and many of them swept laterally to invade the lenticular nucleus. At pallidal levels, the 5-HT axons arborized much less profusely in the external segment than in the internal segment, which contained numerous 5-HT varicose fibers and terminals arranged in a typical bandlike pattern. At striatal levels, the 5-HT terminals were particularly abundant in the ventral striatum, including the nucleus accumbens and deep layers of the olfactory tubercle. They also abounded in the ventrolateral region of the putamen and the ventromedial aspect of the caudate nucleus. Overall, the number of 5-HT fibers and terminals decreased progressively along the rostrocaudal axis of the striatum and several large and elongated zones rather devoid of 5-HT immunoreactivity were visualized, particularly in the caudate nucleus and the dorsal putamen. These zones of poor 5-HT immunoreactivity were in register with similar areas devoid of tyrosine hydroxylase immunoreactivity as seen on contiguous sections. These findings reveal that all the core structures of the basal ganglia in primates receive a significant serotoninergic input, but that the densities and patterns of innervation vary markedly from one structure to the other. PMID- 2212112 TI - Prenatal development of retinogeniculate projections in the rabbit: an HRP study. AB - The prenatal development of the rabbit's retinal projections to the dorsal lateral geniculate nucleus (dLGN) was studied by using anterograde axonal transport of HRP injected intraocularly. Further, the ontogenesis of the dLGN's alpha and beta sectors was studied. Fetuses aged embryonic day 18 (E18) to E29 were examined. Gestation in the rabbit is 30-31 days. On E18 the future dorsal lateral and medial geniculate nuclei appear as a continuous strip of cells along the lateral margin of the dorsal thalamus. On E21 labelled retinal fibers are invading the lateral margin of the dLGN contralateral, but not ipsilateral, to an injected eye. At this age the dorsal lateral and medial geniculate nuclei are separating. By E23 contralateral fibers occupy the entire presumptive alpha sector, while ipsilateral fibers are invading the caudal half of the sector, overlapping the contralateral fibers. At this age the alpha and beta sectors begin to differentiate. On E25 contralateral fibers are more densely distributed throughout the alpha sector and the ipsilateral fibers are concentrated dorsally within the caudal three-quarters of the sector. By E27 contralateral fibers begin to withdraw from a medial zone of the alpha sector, while ipsilateral fibers remain densest in this zone and begin to withdraw from more lateral and caudal aspects of the sector; contralateral fibers, but not ipsilateral fibers, invade the beta sector. At this age the alpha and beta sectors acquire an adult-like appearance. By E29 the contralateral fibers vacate the beta sector and the medial zone of the dLGN and the ipsilateral fibers are restricted to this zone. Thus, 1 or 2 days before birth, the locations of the ipsilateral and contralateral retinal projections to the dLGN resemble those seen in the adult. The early overlapping projections of ipsilateral and contralateral retinal fibers within the dLGN and their eventual segregation in the fetal rabbit are consistent with the development of these projections in other mammalian orders. Further, the brief invasion of the beta sector by the contralateral fibers resembles the transient occupation of the carnivores' perigeniculate nucleus by developing retinal fibers. In addition, direct comparisons of temporal and spatial events during retinal innervation of the dLGN and the superior colliculus indicate several developmental differences between the two nuclei. PMID- 2212113 TI - Three-dimensional structural organization of layer I of the human cerebral cortex: a Golgi study. AB - The three-dimensional structural organization of layer I of the developing and adult human cerebral cortex has been investigated by using sagittal, transverse, and tangential rapid Golgi and Kluver-Barrera preparations. The actual morphology of its fundamental neuron--the Cajal-Retzius cell (C-R)--is established. These large and solitary cells are horizontal multipolar neurons characterized by: (1) long horizontal dendrites that radiate in all directions within a tangential plane parallel to the pial surface, (2) long horizontal axonic collaterals that radiate in all directions within layer I middle level, and (3) a descending axonic process that reaches the lower level, becomes a long tangential fiber--and eventually a myelinated one--and projects in any direction within this level. In cortical ontogenesis, its dendrites, axonic collaterals and terminal axon undergo a progressive multipolar "horizontalization" extending throughout the surface of the expanding cerebral cortex. The neuron's body and main dendrites will be found only in some areas, whereas its axonic collaterals and terminal tangential axon should be found throughout the cerebral cortex. This developmental feature explains the presence of two--middle and lower--plexuses in layer I, composed of the axonic collaterals and the terminal tangential axons of C-R cells, respectively. It is emphasized that the basic morphology of the C-R cell remains essentially unchanged in the course of cortical ontogenesis and that the neuron persists in the adult cerebral cortex. Whereas the C-R cell is the basic neuron of layer I, the pyramidal cells dendritic bouquets represent its larger and main receptive surface (the only one early in development). By the 30th week of gestation, a C-R cell could establish: (1) proximal contacts, through its axonic collaterals, with all dendritic bouquets within a approximately 350 microns radius, and (2) distant contacts, through its tangential axon, with dendritic bouquets within a narrow sagittal, transverse, or diagonal territory several mm long. In cortical ontogenesis, the C-R cells' functional territories continue to expand throughout the surface of the cerebral cortex and possibly overlap with each other. It is proposed that the C-R cell receives inputs from primitive (mesencephalic?) corticipetal fibers and that it transmits the same kind of information (perhaps a basal tone?) to the dendritic bouquets of all pyramidal neurons throughout the cerebral cortex regardless of their location, cortical depth, or functional role. PMID- 2212114 TI - The many faces and phases of borreliosis. I. Lyme disease. AB - Lyme disease is increasingly being reported throughout the United States and many parts of the world. Borrelia burgdorferi, the etiologic agent of Lyme disease, is a spirochete that, not unlike the treponema of syphilis, can cause a spectrum of disease from the initial skin lesion, through widely varied symptoms and signs, to chronic neurologic and arthritic disability. The borrelial spirochete and Lyme disease are the subject of this review. A subsequent article will review other definite and possible cutaneous manifestations of borreliosis. PMID- 2212115 TI - Clinical manifestations in anticardiolipin antibody-positive patients with progressive systemic sclerosis. AB - Anticardiolipin antibody-positive patients with progressive systemic sclerosis were analyzed. Elevated anticardiolipin antibody titers were observed in 13 of 40 cases (33%). Anticardiolipin antibody titer was significantly higher in patients with progressive systemic sclerosis type 1 than in those with type 2 or type 3. Occurrence of anticardiolipin antibody was significantly more frequent in patients positive for anti-nRNP antibodies, rheumatoid factor, or thrombocytopenia. In contrast, patients with proximal scleroderma, scarring, or esophageal hypomotility were positive for anticardiolipin antibody less frequently. These results suggest that anticardiolipin antibody might be closely associated with lupuslike clinical manifestations in a subset of progressive systemic sclerosis or definite progressive systemic sclerosis with thrombocytopenia, rheumatoid factor, or anti-nRNP antibodies. PMID- 2212116 TI - Activation and inducer subset phenotype of the lymphocytic infiltrate around epidermally derived tumors. AB - An in situ analysis of the mononuclear cell infiltrate found in association with a range of benign, premalignant, and malignant epidermal tumors is described. The predominant cell phenotype was that of the recently described immunoregulatory helper/inducer T lymphocyte. A large number of lymphocytes expressed antigens associated with cellular activation, suggesting an ongoing immunologic response by the host against the tumor, although evidence of in situ proliferation of these cells was lacking. These findings suggest that the infiltrate found in association with cutaneous tumors does not represent passive accumulation of lymphocytes from the circulation but rather an active antitumor response. PMID- 2212117 TI - Photochemotherapy improves chronic cutaneous graft-versus-host disease. AB - We have used oral psoralen photochemotherapy (PUVA) to treat four patients with chronic graft-versus-host disease of the skin, oral mucosa, and liver, who had responded only partially to long-term immunosuppressive therapy (prednisolone, cyclosporine, azathioprine). PUVA therapy was delivered to the entire skin but not to the oral mucosa, and immunosuppressive therapy was continued in all patients. Two patients' skin lesions improved considerably; the oral lesions healed and did not recur in one. Immunosuppressive therapy could be reduced in these two patients. One patient with sicca signs did not improve. One patient had to interrupt PUVA therapy because of side effects attributed to 8-methoxypsoralen (nausea and vomiting). No flare of acute cutaneous graft-versus-host disease was noted during PUVA therapy. Chronic graft-versus-host disease of the liver did not improve in any patient. PMID- 2212118 TI - Benign lymphangioendothelioma. AB - We have studied eight cases of an acquired lymphatic endothelial lesion for which we propose the name "benign lymphangioendothelioma." The lesions developed as solitary, slowly extending, erythematous macules and plaques, usually occurring on the extremities or the shoulders in adolescents or adults. The characteristic histopathologic feature is permeation of the dermal collagen by flattened, endothelium-lined channels and spaces. Hemorrhage, iron deposition, and inflammation were not part of the lesion. Ulex europaeus agglutinin I labeled the lesional endothelial cells consistently, but factor VIII-related antigen labeling was negative. This histologic pattern and the special studies suggested a lymphatic lesion. Surgical excision, performed in six patients, was not followed by recurrence. PMID- 2212119 TI - Absence of estrogen receptors in dysplastic nevi and malignant melanoma. AB - Benign nevi, dysplastic nevi, and primary and metastatic malignant melanomas were evaluated for the presence of sex hormone binding and estrogen receptor protein. We have confirmed the observation of Ellis et al. that some pigmented lesions possess sex hormone-binding proteins. We could not demonstrate a true estrogen receptor in any benign nevi, dysplastic nevi, primary melanomas, or metastatic melanomas. Thus the ability to bind estrogen or progesterone does not correlate with the presence of a true estrogen receptor. Lack of nuclear estrogen receptors suggests that the influence of estrogen on the pathophysiology of melanoma or of benign melanocytic nevi may not be significant. PMID- 2212121 TI - Localized hyperhidrosis in pretibial myxedema. AB - Two cases of spontaneous hyperhidrosis limited to pretibial myxedema lesions were studied. Quantitative measurements of stimulated eccrine sweat were made after the intradermal injection of methacholine. The sweat rate was two to four times greater in the lesional skin than in perilesional skin. Eccrine secretory glands in excisional biopsy specimens from the pretibial lesions were significantly larger than those in perilesional skin. To our knowledge, hyperhidrosis localized to areas of pretibial myxedema has not been reported. PMID- 2212120 TI - Neutrophilic dermatosis with myelodysplastic syndrome: nuclear segmentation anomalies of neutrophils in the skin lesion and in peripheral blood. AB - Neutrophilic dermatosis developed in two patients with myelodysplastic syndrome. Biopsy specimens of their skin lesions showed marked infiltration by neutrophils with nuclear anomalies, that is, hyposegmentation (pseudo-Pelger-Huet anomaly) or hypersegmentation. Peripheral blood and bone marrow neutrophils had similar anomalies. To our knowledge, this is the first report of nuclear segmentation anomalies of neutrophils in neutrophilic dermatosis skin lesions of patients with myelodysplastic syndrome. PMID- 2212122 TI - Chilblains (perniosis). AB - Unfamiliarity of physicians with chilblains (perniosis) gives rise to unnecessary hospital admissions with expensive laboratory and radiologic evaluations and, at times, hazardous therapy. Seven cases of chilblains were seen in San Francisco from November 1986 through January 1987. The patients presented with pruritic, at times painful, purple acral patches or plaques on the fingers, toes, and nose after exposure to a cool or a cold, damp environment. Histologic examination in two cases revealed a perivascular lymphocytic infiltrate with endothelial swelling of the subcutaneous fat and of the upper and lower dermal plexus. PMID- 2212124 TI - Cutaneous surgery and the pregnant patient. AB - Cutaneous surgery in 34 pregnant women is described. The main indication for surgery was the diagnosis and/or treatment of malignancy. Surgery during the period of organogenesis (15 to 56 days) should be avoided when possible. Patients should be positioned on the left side during the procedure to avoid the supine hypotensive syndrome. Monitoring of the fetal heartbeat is desirable. Local anesthetics, penicillin, and erythromycin are safe if used carefully. Acetaminophen is the analgesic of choice. Exposure to the sun should be avoided during the perioperative period. PMID- 2212123 TI - Platelet activating factor-induced clinical and histopathologic responses in atopic skin and their modification by the platelet activating factor antagonist BN52063. AB - The clinical and histopathologic responses to intradermal platelet-activating factor (PAF-acether) in atopic subjects, without evidence of atopic dermatitis are documented. An immediate acute wheal and flare reaction was observed in all volunteers. Histopathologically, the reaction was characterized by a predominantly neutrophilic response, which was seen at 30 minutes and was maximal at 4 hours. Eosinophils were observed in the infiltrate as early as 30 minutes after injection, and were maximal by 12 hours. The specific PAF-acether antagonist BN52063 antagonized the acute flare response to intradermal PAF acether but had little effect on cellular recruitment at the site of injection. PMID- 2212125 TI - Dermatologic therapy: 1989. PMID- 2212126 TI - Comparison of methods for checking surgical margins. AB - Surgical margins of a cutaneous neoplasm can be evaluated by various combinations of three major types of sections: vertical (perpendicular), horizontal (parallel), and oblique (Mohs method). Vertical sections may run transversely through tumor (breadloaf method), longitudinally through tumor (breadloaf-cross method), or peripheral to the tumor. The peripheral (perimeter) sectioning methods are the only methods that can evaluate almost 100% of the margin, but they have the disadvantage of not showing the relationship of the tumor to its margin, which can be seen clearly with the vertical transverse sections. Seven methods of checking surgical margins are compared and contrasted. None of these is judged to be perfect or best. PMID- 2212127 TI - Diseases of the dermis. PMID- 2212128 TI - Years of potential life lost: another indicator of the impact of cutaneous malignant melanoma on society. AB - Years of potential life lost (YPLL) is an indicator of premature mortality that complements traditional incidence and mortality rates and that facilitates comparisons among different cancers. We calculated YPLL from cutaneous melanoma and 11 other cancers routinely recorded and tracked by Surveillance, Epidemiology and End Results (SEER). YPLL from cutaneous melanoma ranked eighth for persons younger than 65 years of age and fourth for those 20 to 49 years of age. An average of 17.1 YPLL per death were due to melanoma, one of the highest rates for adult-onset cancers. The results of our study, the first to apply YPLL to cutaneous melanoma, emphasize the disproportionate impact of this cancer on young and middle-aged adults and reemphasize the importance of this cancer as a public health priority. PMID- 2212130 TI - Cryosurgical management of basal cell carcinoma of the eyelid: a 10-year experience. PMID- 2212129 TI - Dermatology and the history of ideas. PMID- 2212131 TI - Basal cell carcinoma presenting as a chronic finger ulcer. PMID- 2212132 TI - Cyclosporine and methotrexate: a dangerous combination. PMID- 2212133 TI - The thumbprint sign: rapid diagnosis of disseminated strongyloidiasis. PMID- 2212134 TI - Kindler syndrome and epidermolysis bullosa simplex. PMID- 2212135 TI - Measurement of transepidermal water loss. PMID- 2212136 TI - Bullous pemphigoid and multiple sclerosis. PMID- 2212137 TI - Skin hyperreactivity response (pathergy) in Behcet's disease: usefulness of direct immunofluorescence. PMID- 2212138 TI - The many faces and phases of borreliosis II. AB - Borrelia burgdorferi, the etiologic agent of Lyme disease, has also been associated with other cutaneous conditions. Acrodermatitis chronica atrophicans and lymphadenosis benigna cutis are also caused by B. burgdorferi. Recent evidence links some cases of progressive facial hemiatrophy of Parry-Romberg, benign lymphocytic infiltrate of the skin (Jessner-Kanof), lichen sclerosus et atrophicus, morphea, and Shulman syndrome with borreliae. This article reviews the manifestations of the diseases definitely linked to borreliosis and the evidence linking borreliae to progressive facial hemiatrophy, benign lymphocytic infiltrate, lichen sclerosus et atrophicus, morphea, and Shulman syndrome. PMID- 2212139 TI - Trends in basal cell carcinoma, squamous cell carcinoma, and melanoma of the skin from 1973 through 1987. AB - Major increases have occurred in the incidence of basal cell carcinoma and squamous cell carcinoma of the skin, as well as in cutaneous malignant melanoma during the period 1973 through 1987 in British Columbia. The greatest increases in basal and squamous cell carcinomas are on the head and neck. This indicates that exposure to sunlight is the major causative factor. The greatest increase in melanoma is on the trunk in men and on the lower limbs in women. The dramatic increases in nonmelanoma skin cancers in British Columbia, a relatively low sunlight area, suggest that major prevention programs are needed in areas that are not considered "sunspots." PMID- 2212141 TI - A method for the determination of UVA protection for normal skin. AB - Although the UVB portion of the electromagnetic spectrum (290 to 320 nm) is responsible for most of the harmful effects of sunlight on the skin, wavelengths in the UVA region also contribute to photodamage. A simple and rapid clinical test, the sun protection factor determination, is available to assess the sunburn protective effect of a sunscreen, primarily a UVB effect. However, no practical test has been proposed to measure a sunscreen's UVA protection. We described a method for the calculation of UVA protection in normal subjects. The determination of UVA protection involves three steps: (1) the UV absorbance spectrum of the sunscreen on skin is determined spectrophotometrically; (2) a convolution spectrum is calculated by multiplying the solar spectrum with the Commission Internationale de l'Eclairage UV Hazard Spectrum; and (3) the sunscreen transmission spectrum is then incorporated into the convolution spectrum to obtain the UVA effectiveness ratio, which can be expressed as the UVA protection percentage. Because the UVA protection percentage value is based both on normal erythemic risk and on standard sunlight, the protection for any product can be easily measured. The procedure is simple, and values generated can be reproduced in other laboratories. PMID- 2212140 TI - Cutaneous lesions of disseminated histoplasmosis in human immunodeficiency virus infected patients. AB - Disseminated histoplasmosis is being diagnosed more frequently in persons infected with the human immunodeficiency virus and is often the initial manifestation of the acquired immunodeficiency syndrome (AIDS). Disease-related cutaneous features of HIV-associated disseminated histoplasmosis are defined as mucocutaneous lesions from which fungal organisms were either cultured or demonstrated histopathologically. We report four HIV-seropositive patients with disseminated histoplasmosis who had culture-positive skin or oral lesions of histoplasmosis and review the specific cutaneous manifestations of HIV-associated disseminated histoplasmosis. Including our patients, disease-related skin and/or mucosal lesions were present in 11% of patients (26% of 239) with HIV-associated disseminated histoplasmosis. The possibility of disseminated histoplasmosis should be considered in all HIV-infected persons and in persons with AIDS risk factors who have fever, weight loss, hepatosplenomegaly, and new cutaneous lesions. An early skin or mucosal biopsy specimen for crushed tissue preparation, histologic evaluation, and fungal culture is a simple, rapid diagnostic procedure. PMID- 2212142 TI - Cheilitis granulomatosa: report of six cases and review of the literature. AB - Six cases of cheilitis granulomatosa, a rare inflammatory disorder of unknown origin, are reported. The condition produces nontender, persistent swelling of one or both lips and affects primarily young adults. Histologically, nonnecrotizing granulomatous inflammation is seen. The clinical findings and results of therapy in these six cases are presented. One patient was treated with hydroxychloroquine sulfate (Plaquenil) that stabilized the process. One of our patients had vesicular-appearing lesions. Microscopic examination showed the lesions to be dilated superficial lymphatic channels, a finding that to our knowledge has not been previously described. PMID- 2212143 TI - Scleroderma and L-tryptophan: a possible explanation of the eosinophilia-myalgia syndrome. AB - Scleroderma developed in six women who were taking L-tryptophan. Fasciitis and morphea were most common, but one patient had pleural effusion, hypertension, and signs of cardiac and kidney failure. In five patients the biopsy findings were characteristic of scleroderma; the sixth patient had Crohn's disease and developed fasciitis; her biopsy specimen showed inflammatory arteritis. All patients' conditions improved after cessation of their L-tryptophan intake, initiation of corticosteroid therapy, or both. These findings confirm previous data that show altered tryptophan-kynurenine metabolism in some patients with scleroderma and fasciitis, particularly with tryptophan loading. PMID- 2212144 TI - Correlation between the drug penetration and the blanching effect of topically applied hydrocortisone creams in human beings. AB - Two topical formulations of 2.5% hydrocortisone were tested to investigate the possible correlation between the blanching response of topically applied hydrocortisone and its release from the formulation after its penetration into the stratum corneum. After application of the cream, the stratum corneum was removed at different intervals and the hydrocortisone content was measured by radioimmunoassay. The blanching responses (expressed as mean score vs time) showed a 1.5-fold difference (significant at p = 0.0026) between the two creams at the maximum effect, which was reached for both creams after 16 hours. The amounts of hydrocortisone present in the stratum corneum after every application period showed a twofold difference (p = 0.0001) between the two creams. However, in contrast to the blanching, these quantities remained constant from 4 to 24 hours. This steady state characteristic may be partially due to the use of occlusion and to the excess formulation remaining at the surface. Although there is no parallelism with time between the results of the two methods, both give clear evidence of a difference in stratum corneum penetration and pharmacologic activity of the two formulations. Drug penetrations and pharmacodynamic activities of the two creams can be correlated with in vitro release characteristics. PMID- 2212146 TI - Transdermal viprostol in the treatment of male pattern baldness. AB - Fifty-seven men were randomly assigned for treatment of androgenetic alopecia with viprostol, vehicle, or placebo twice daily for 24 weeks. Nonvellus hair growth was assessed subjectively by both patient and investigator and objectively through hair counts from macrophotographs of the target area. Nonvellus target area hair counts declined in all three treatment groups at the end of the 6-month study. Viprostol is not an effective hair growth promoter in androgenetic alopecia. PMID- 2212145 TI - Treatment of hirsutism with the pure antiandrogen flutamide. AB - The effectiveness of the antiandrogen flutamide in combination with an oral contraceptive was studied in 20 patients with moderate to severe hirsutism. Eight patients had no previous therapy, whereas 12 had failed to respond to oral contraceptives, spironolactone, or dexamethasone therapy. Treatment with the antiandrogen flutamide (250 mg twice daily) and an oral contraceptive (Ortho 1/35) resulted in a particularly rapid and marked decrease in the total hirsutism score, which reached the normal range at 7 months. Seborrhea, acne, and hair loss score were also rapidly corrected. Treatment was associated with a decrease in plasma luteinizing hormone, progesterone, and estradiol levels. Plasma sex hormone-binding globulin levels were initially low in 18 to 20 patients but increased significantly during therapy. No clinically significant side effects were observed. PMID- 2212147 TI - Pityriasis lichenoides in children: a long-term follow-up of eighty-nine cases. AB - Pityriasis lichenoides is usually classified into an acute and a chronic form. From a review of 89 cases of the disease seen since 1974 it seems that a more realistic classification into three main groups, according to the distribution of pityriasis lichenoides lesions, could be made, namely, a diffuse, a central, and a peripheral form, each characterized by a different clinical course. Conversely, no correlations were detected in our series between the severity of skin lesions and their distribution or the overall course of the disease. None of our cases suggests the possible evolution of pityriasis lichenoides into lymphomatoid papulosis. Although no infectious causative agent has been identified, a viral origin seems likely in some cases. Most patients responded favorably to UVB irradiation. Our conclusions are (1) that pityriasis lichenoides is probably a clinical disorder with a diverse etiology and (2) that its classification by distribution seems more useful than its subdivision into an acute and a chronic form. PMID- 2212148 TI - Piroxicam-induced photosensitivity and contact sensitivity to thiosalicylic acid. AB - A photocontact dermatitis developed in three patients after the application of gel containing 0.5% piroxicam. Patch tests were positive to thiomersal and thiosalicylic acid. Photopatch tests with piroxicam at several concentrations were positive in the three patients but negative in 62 normal volunteer subjects. Patch tests performed on 14 patients with proved systemic photosensitivity to piroxicam were positive for thiomersal and thiosalicylic acid. Nine of 12 patients previously sensitized to thiosalicylic acid and with no history of exposure to piroxicam showed positive photopatch test reactions to this chemical. These results support a relation between piroxicam-induced photosensitivity and contact sensitivity to thiosalicylic acid. Contact allergic sensitivity to the latter is a marker for patients with a high risk of developing photosensitivity reactions to piroxicam. These reactions may be due to photoproducts of the drug rather than metabolites. PMID- 2212149 TI - Hydroxychloroquine is effective therapy for control of cutaneous sarcoidal granulomas. AB - Cutaneous sarcoidosis often responds poorly to topical and intralesional corticosteroids but may respond to moderate to high doses of oral corticosteroids. To avoid the use of systemic corticosteroids, we treated 17 patients with cutaneous sarcoidal granulomas with hydroxychloroquine (2 to 3 mg/kg/day) in an open clinical trial. If response occurred, other medications were first tapered and then the hydroxychloroquine dosage was reduced or stopped. The cutaneous lesions of 12 patients regressed within 4 to 12 weeks, and they were able to stop other therapies; three patients had a partial response, and two patients had no regression. Two of eight patients with pulmonary sarcoidosis improved. No ocular toxicity was noted. PMID- 2212151 TI - Dermatoses associated with sterile lytic bone lesions. AB - In recent years several dermatoses, palmoplantar pustulosis, acne fulminans, and Sweet's syndrome, have been associated with sterile lytic bone lesions. This article discusses the clinical, laboratory, and histologic findings of these disorders and postulates a common mechanism underlying the bone lesions. PMID- 2212150 TI - Treatment of aggressive keratoacanthomas by radiotherapy. AB - Keratoacanthomas infrequently are treated by radiotherapy. However, keratoacanthomas that are recurrent after surgical excision or whose resection would result in cosmetic deformity may benefit from radiotherapy. Between January 1970 and June 1988, 29 such keratoacanthomas in 18 patients were irradiated. Doses ranged from 3500 cGy in 15 fractions to 5600 cGy in 28 fractions. Measured end points of therapy were (1) initial response, (2) freedom from recurrence, and (3) quality of the subsequent cosmetic appearance (scored as good, fair, or poor). No lesion progressed and all eventually regressed completely. Cosmetic results generally were considered good by both the patient and the referring dermatologist; none of the results was considered poor. Our results demonstrate that radiation is an effective means of treating keratoacanthomas. PMID- 2212152 TI - The relationship of pemphigus to neoplasia. AB - A statistically increased incidence of malignancy has been observed in patients with pemphigus. A review of the literature reveals 42 cases of nonthymic malignancies and 18 cases of thymic malignancies. A significant predominance of men, with mean age at onset of 50 years, was observed. Pemphigus vulgaris is more common in patients with nonthymic neoplasms, whereas pemphigus foliaceus or pemphigus erythematosus and pemphigus vulgaris are equally common in patients with thymic neoplasms. Lymphoreticular malignancies, especially Kaposi's sarcoma, are most frequently observed. The majority of patients with nonthymic neoplasms have pemphigus before the detection of the malignancy and have a favorable 5-year survival rate after tumor resection. The majority of the patients with thymic neoplasms have a thymoma before the development of pemphigus. In some patients pemphigus develops after thymectomy and myasthenia gravis is often associated. Overall, 37 of the 60 patients, or 61%, had a neoplasm of the immune system. PMID- 2212154 TI - Computer-generated operative reports. How to save up to 30 minutes per day. PMID- 2212153 TI - Sweet's syndrome: a clinicopathologic review of twenty-nine cases. AB - Twenty-nine patients with Sweet's syndrome were studied. Not all of Sweet's original criteria were necessarily present and diagnosis was dependent on the recognition of the typical, acute, tender, erythematous plaques and the characteristic histologic features of a neutrophilic infiltrate with leukocytoclasis. Women are affected much more frequently than men. The origin of Sweet's syndrome is still unclear, but an underlying disease was found in more than 50% of our cases. A streptococcal infection was evident in six cases, inflammatory bowel disease in three cases, malignancy in four cases, and pregnancy in two others. Treatment with oral prednisolone for an average of 6 weeks was the usual treatment, although in four patients the disease cleared spontaneously. Resolution of the eruption is occasionally followed by milia and scarring. Recurrences are common and affect up to one third of patients. PMID- 2212155 TI - Dramatic tissue artifact that mimics morphea or scleroderma. PMID- 2212156 TI - Occult primary syphilis: the nonerosive chancre. PMID- 2212157 TI - Acrodermatitis continua-type of pustular psoriasis responds to low-dose cyclosporine. PMID- 2212158 TI - Prevalence of the early warning signs of melanoma among participants in the 1989 Rhode Island skin cancer screening. PMID- 2212159 TI - Primary oral Kaposi's sarcoma of the hard palate. PMID- 2212160 TI - Arachnoid cyst in a patient with basal cell nevus syndrome. PMID- 2212161 TI - Pemphigus vulgaris presenting as a nodular lesion. PMID- 2212162 TI - Recurrent aphthous ulcer in patient infected with human immunodeficiency virus: successful treatment with thalidomide. PMID- 2212164 TI - Qualifications of the provider. PMID- 2212163 TI - Dramatic follicular plugging in pityriasis rubra pilaris. PMID- 2212165 TI - Nalmefene and pruritus. PMID- 2212166 TI - Pemphigus vulgaris and squamous cell carcinoma of the lung. PMID- 2212167 TI - Acral persistent papular mucinosis: a distinct entity. PMID- 2212168 TI - Discoid lupus erythematosus. PMID- 2212169 TI - Deficient conversion of linoleic acid. PMID- 2212170 TI - Treatment of fungal skin infections: state of the art. AB - The number of cases of mycotic infections are increasing, presenting physicians today with an unprecedented challenge in handling the treatment and prophylactic control of these disorders. The increase in mycotic disorders is due to many factors, such as longer life span, organ transplantation, and the acquired immunodeficiency syndrome. The pharmaceutical industry is providing physicians with newer, more potent drugs to manage mycoses. An overview of current practice in the use of topical and oral agents, especially ketoconazole, are given in the following specific mycoses: tinea capitis, pityriasis versicolor, seborrheic dermatitis, Trichophyton rubrum infections, vaginal candidiasis, and moist intertriginous tineas. The efficacy of ketoconazole in various vehicles and dosage schedules and of traditional agents such as griseofulvin are discussed with relation to each of the mycoses. PMID- 2212171 TI - Treatment of vaginal candidiasis: orally or vaginally? AB - Vaginal candidiasis continues to be the most common cause of vaginal discharge. A large variety of topical drugs and a selection of orally active antifungals are currently available. The choice between the use of oral drugs or intravaginal agents will depend on the therapeutic results obtained with the different agents, side effects, pregnancy status, and patient preference. The results obtained in the Maria Hospital, Tilburg, The Netherlands, and a review of foreign data suggest the following: (1) For acute infection oral and topical agents produce equivalent results. (2) For chronic infections oral medication is preferred. (3) Oral therapy should not be given to pregnant patients or to patients not using reliable contraceptive measures. (4) Half the patients prefer oral medication; only 5% prefer intravaginal therapy, and the others had no clear preference. PMID- 2212173 TI - Alcohol and drug use among youth. PMID- 2212172 TI - Individualizing treatment of vaginal candidiasis. AB - Clinicians have a vast array of effective antimycotics for the treatment of vaginal candidiasis. Multiple topical formulations are available, yet there is little evidence to suggest that formulation per se influences outcome. A growing number of highly effective oral systemic antimycotic agents provide the practitioner with additional options. Treatment regimens have also changed with the introduction of shorter, often single-day/single-dose courses of therapy. Not all therapeutic agents have the same activity against vaginal fungal pathogens in that topical azoles tend to be more active than nystatin. Differences in patient characteristics, however, are more important than the differences between antimycotic agents and therapeutic regimens in determining selection of the appropriate antimycotic. Patients with vaginal candidiasis vary with regard to duration and severity of symptoms and past frequency of attacks, distribution of inflammation, and pregnancy status. The clinician should consider all these variables both in selecting the appropriate antimycotic agent and the route of administration and in planning the duration of therapy. Individualized therapy offers additional benefits to patients, who may then enjoy the maximum advantages of antimycotics now available. PMID- 2212174 TI - Adolescent drug use: findings of national and local surveys. AB - Adolescent drug use increased until about 1981, but since then it has steadily declined. Current data show some drug use in the 4th and 5th grades and considerable increases from the 6th to the 9th grades. For drugs such as marijuana, cocaine, and stimulants, lifetime prevalence continues to increase through high school; for drugs such as inhalants and heroin, lifetime prevalence may decline for Grades 10, 11, and 12, suggesting that students who use these drugs early may drop out. Drug use of rural youth is similar to that of other youth. Barrio, ghetto, and Native-American reservation youth may have high rates of use, but use of Black and Hispanic seniors may be equivalent to or less than that of White seniors. National data and broadly defined ethnic data, however, may cover up important subgroup differences. For example, Western Mexican American girls have lower use than Western Spanish-American girls, possibly because of the greater influence of "marianisma." Different locations may also have very different patterns of adolescent drug use, calling for different types of local intervention. PMID- 2212175 TI - A social stress model of substance abuse. AB - The social stress model provides a framework for detecting protective factors that may contribute to adolescents' resiliency when confronted with compelling influences to engage in substance abuse. Parameters of the model were tested in 2 urban high school samples (N = 124) of Black (78%), White (16%), and Hispanic (6%) adolescents aged 12-14 years. Pretest and posttest measures, designed to detect the relative influence of stress, social networks, social competencies, and community resources on levels of students' usage, were completed at the beginning and end of the school year. The parameters of the model, estimated using LISREL7, indicated that the pathway from family characteristics to usage and from assertion to usage were significant. The paths from the remaining hypothesized variables were not significant. Implications for the design of prevention programs that facilitate youths' resiliency are discussed. PMID- 2212176 TI - Drug use among pregnant adolescents. AB - Despite concern over the co-occurrence of substance use, unplanned pregnancy and other problem behaviors in adolescence, little information is available on substance use before, during, and after adolescent pregnancy. The authors report data from the first 100 Ss enrolled in an ongoing longitudinal study on drug use before and during pregnancy in adolescence. Unmarried pregnant adolescents, ages 17 and under, were recruited for the study from urban alternative school programs and community social and health service agencies. Findings indicate that although lifetime prevalence of drug use was relatively high and pregnant respondents appear embedded in drug prevalent environments, substance use declined voluntarily and substantially during pregnancy. Prepregnancy drug use predicted substance use during pregnancy, but neither best friends' nor boyfriends' use of alcohol or marijuana predicted subjects' use of these substances during pregnancy after taking prepregnancy use into account. PMID- 2212177 TI - Substance abuse among Native-American youth. AB - Substance use and abuse poses serious risks for American-Indian youth, their families, and their communities. This article briefly reviews the relevant social epidemiological data followed by a discussion of culturally relevant etiological factors. Current strategies for identification of youth at high risk for substance use are highlighted, concentrating primarily on the theoretical and methodological aspects appropriate for this population. In this context, data from recent work are reported. Given the nascent state of culturally appropriate prevention technology, issues of sensitive technology transfer and stereotyping are discussed in the context of current research. Study results from this sample, although dramatic, should not be overgeneralized to all American-Indian youth. PMID- 2212178 TI - Preventing drug use in adolescents through media interventions. AB - The communications media, and the broadcast media in particular, have been disseminating an increasing volume of antidrug messages over the past several years. Many American business leaders believe that the media can help to reduce drug use, and they have supported a nationwide effort to highlight the dangers of illicit drug use on the airwaves and in newspapers and magazines. This article considers the efficacy of media-based efforts to prevent adolescent drug use. Selected theories and research are reviewed, and suggestions are made for integrating social and behavioral theory and research into media prevention strategies. The authors conclude that scientists and interventionists could do much to improve on current research and development in this prevention arena, within the limits of what is possible to achieve through mass communications as presently constituted in the United States. PMID- 2212179 TI - Computer-assisted strategies for substance abuse prevention: opportunities and barriers. AB - This article presents an analysis of the potential role that computer-assisted strategies could play in substance abuse prevention efforts in the future. Four primary areas are addressed. First, substance abuse prevention is discussed within the context of adolescent development. Second, computer-assisted instruction (CAI) is defined in terms of the opportunities it represents for substance abuse prevention. Third, a variety of barriers are described that must be addressed if the potential of CAI for enhancing substance abuse prevention efforts is ever to be realized. Finally, recommendations are made for coordinating research and development efforts, now and in the future, so that the potential of new technology for improving substance abuse prevention efforts will be adequately evaluated. PMID- 2212180 TI - Self-instruction to prevent HIV infection among African-American and Hispanic American adolescents. AB - This study tested the efficacy of self-instruction intervention to reduce avoidable risks for HIV infection associated with drug use and unsafe sexual activity among African-American and Hispanic adolescents (N = 60). After completing pretests, adolescent participants in the study were randomly divided into three conditions. Participants in one condition received a self instructional guide about AIDS and its transmission along with group instruction in using the guide. Adolescents in another condition received the guide without group instruction. Participants in the third condition received neither the guide nor group instruction. Outcome findings indicate that participants in the two self-instruction conditions improved more between pretest and posttest assessments on measures of HIV infection risk compared with adolescents in the control condition. PMID- 2212181 TI - Preventing adolescent drug abuse through a multimodal cognitive-behavioral approach: results of a 3-year study. AB - Students (N = 4,466) attending 56 schools in New York State were involved in a 3 year study testing the effectiveness of a cognitive-behavioral approach to substance abuse prevention. In a randomized block design, schools were assigned to receive (a) the prevention program with formal provider training and implementation feedback, (b) the prevention program with videotaped provider training and no feedback, or (c) no treatment. After pretest equivalence and comparability of conditions with respect to attrition were established, students who received at least 60% of the prevention program (N = 3,684) were included in analyses of program effectiveness. Significant prevention effects were found for cigarette smoking, marijuana use, and immoderate alcohol use. Prevention effects were also found for normative expectations and knowledge concerning substance use, interpersonal skills, and communication skills. PMID- 2212182 TI - Relative effectiveness of comprehensive community programming for drug abuse prevention with high-risk and low-risk adolescents. AB - This article reviews major risk factors for cigarette smoking, alcohol, and other drug abuse and promising community-based approaches to primary prevention. In a longitudinal experimental study, 8 representative Kansas City communities were assigned randomly to program (school, parent, mass media, and community organization) and control (mass media and community organization only) conditions. Programs were delivered at either 6th or 7th grade, and panels were followed through Grade 9 or 10. The primary findings were (a) significant reductions at 3 years in tobacco and marijuana use and (b) equivalent reductions for youth at different levels of risk. This study provides evidence that a comprehensive community program-based approach can prevent the onset of substance abuse and that the benefits are experienced equally by youth at high and low risk. PMID- 2212183 TI - Planning for the appropriate analysis in school-based drug-use prevention studies. AB - School-based drug-use prevention studies often apply interventions to entire schools. A major problem for these studies results from the intragroup dependence often seen when intact social groups are assigned to study conditions. Analysis of data from 2 such studies revealed intraclass correlation coefficients between 0.02 and 0.05 for common drug use measures. Because even such modest intragroup dependence can invalidate the traditional fixed-effects analyses, researchers should adopt alternative methods that acknowledge this dependence. These alternative methods are reviewed, and appropriate methods for computing sample size requirements are illustrated. Investigators should consider these analysis issues when planning future studies, because the number of schools required for an unbiased analysis may be substantially greater than for the traditional methods. PMID- 2212185 TI - Patient suitability and outcome in short-term individual psychotherapy. AB - The effects of short-term (time-limited), dynamically oriented individual therapy and the patient characteristic quality of object relations (QOR) were studied in a controlled clinical trial involving 8 experienced therapists and 144 psychiatric outpatients. A comprehensive set of outcome scores was monitored at 5 month intervals including a follow-up assessment. A strong treatment effect that was maintained at follow-up was found. The effect was evident in terms of statistical significance, effect size, and clinical significance. Evidence for an additive effect of the combination of treatment and QOR was also found. The best results were attained by high QOR therapy patients, and the worst results were attained by low QOR control patients. The results were suggestive of an optimal match between type of patient and type of therapy. PMID- 2212184 TI - Hero/heroine modeling for Puerto Rican adolescents: a preventive mental health intervention. AB - Culturally sensitive treatments of the special mental health needs of high-risk Puerto Rican adolescents are lacking. The hero/heroine intervention was based on adult Puerto Rican role models to foster ethnic identity, self-concept, and adaptive coping behavior. 90 nonclinical Puerto Rican 8th and 9th graders were screened for presenting behavior problems in school and randomly assigned to an intervention and a control group. After 19 sessions, the intervention significantly increased adolescents' ethnic identity and self-concept and reduced anxiety. Treatment outcomes varied as a function of grade level, sex, and household composition. Self-concept was negatively affected among girls from intact families. The study supports the effectiveness of the culturally sensitive modality as a preventive mental health intervention for high-risk Puerto Rican adolescents, especially from single-parent families. PMID- 2212186 TI - Relative endurance of unipolar depression treatment effects: longitudinal follow up. AB - This study represents a 2.25-year follow-up to a treatment study reported earlier (McLean & Hakstian, 1979) in which 121 unipolar depressed outpatients were treated by either (a) nondirective psychotherapy, (b) behavior therapy, (c) pharmacotherapy, or (d) relaxation therapy. A nondepressed, normal control group was evaluated on the same 28 measures and 6 intervals for contrast purposes. Behavior therapy patients alone were significantly improved in the areas of mood, personal productivity, and social activity, relative to treatment control patients over the follow-up period. Also, twice as many behavior therapy patients (i.e., 64%) fell within one standard deviation of the normal, nondepressed control group distribution on depressed mood, compared with non-directive psychotherapy and pharmacotherapy patients, when scores were aggregated across the 6 assessment points. PMID- 2212187 TI - Reversal theory and smoking: a state-based approach to ex-smokers' highly tempting situations. AB - Reversal theory provides a new approach to understanding ex-smokers' behavior during highly tempting situations. Hypotheses derived from the theory were tested in 2 studies of the highly tempting situations of ex-smokers drawn from community smoking cessation programs. Study 1 consisted of interviews with 55 Ss (25 men and 30 women, mean age 37 years) conducted 3 months after cessation. Study 2 consisted of interviews with 104 Ss (45 men and 59 women, mean age 41 years) conducted 6, 9, 12, and 15 months after cessation. All interviews were coded using reversal theory constructs. Results supported the hypotheses that individuals in paratelic or negativistic states were more likely to lapse than individuals in telic/conformist states and that cigarette availability was related to lapses in paratelic, but not telic, states. Reversal theory constructs accurately classified 93% and 85% of the cases, suggesting that the theory provides an improved model for understanding behavior during highly tempting situations. PMID- 2212189 TI - Does marital agony precede marital ecstasy? A comment on Gottman and Krokoff's "Marital interaction and satisfaction: a longitudinal view". AB - In a recent article, Gottman and Krokoff (1989) presented a fascinating and counterintuitive portrayal of a temporally related dynamic relationship of marital conflict and marital satisfaction. Unfortunately the results from which their conclusions spring are quite problematic. In a 2-wave, extreme-groups design, Gottman and Krokoff used raw change in satisfaction as a correlate of Time 1 conflict variables for purposes of analysis. Serious psychometric questions arise with this approach to the causal assessment of change. Given the considerations raised, there is a high likelihood that Gottman and Krokoff's data result from statistical artifact. Alternative approaches to the measurement of change are discussed in the context of illustrating the problematic components of Gottman and Krokoff's analysis. PMID- 2212190 TI - Ten going on eleven. PMID- 2212188 TI - Guilt in depressed outpatients. AB - This study was designed to determine whether normal control subjects (n = 17) and depressed outpatients (n = 72) differed with respect to the extent and conditions under which they reported dysfunctional guilt. Depressed outpatients reported significantly more guilt than normal control subjects in most types of situations. A family history of depression was related to a higher overall level of guilt in patients. Course and severity of depression and endogenous subtype did not relate to the amount of guilt reported by the patients. This study provides clinical norms on the Situational Guilt Scale (SGS) for a sample of unipolar, nonpsychotic outpatients with major depressive disorder. PMID- 2212191 TI - Prevalence of Streptococcus sobrinus in relation to dental caries in children from Iceland and The Netherlands. AB - The aim of this study was to investigate the presence of S. sobrinus and S. mutans in specimens of dental plaque and saliva of children five years of age in Reykjavik, Iceland (study 1) and in samples of dental plaque from children nine years of age in Amsterdam, The Netherlands (study 2). The immuneblotting technique (IBT) was a suitable method to evaluate the presence and numbers of S. mutans and S. sobrinus in human dental plaque and saliva. In study 1, eighty-four children were evaluated bacteriologically; of these, 73 percent harbored mutans streptococci in their plaque or saliva. S. sobrinus similarly was present in 29 percent of the children. In study 2 (seventy-two children), the corresponding percentages were 81 percent for S. mutans, and 35 percent for S. sobrinus. The latter was detected in 6 percent of the plaque samples exclusive of S. mutans. PMID- 2212193 TI - In vitro fluoride uptake by enamel adjacent to a glass ionomer luting cement. AB - The release of fluoride from a glass ionomer luting agent used to cement an orthodontic band was shown to increase enamel fluoride levels of adjacent teeth in vitro. The fluoride uptake was statistically significant at gingival biopsy sites after one month. There was an inverse relationship between baseline fluoride levels of the biopsied teeth and the amount of fluoride taken up by the enamel. PMID- 2212192 TI - Use of fluoride supplementation by children living in fluoridated communities. AB - As part of a case-control study that investigated risk factors of enamel fluorosis, a fluoride/residency history was obtained covering the first six years of life by means of a mailed questionnaire, with a reliability factor of 90 percent. Of the 677 participating seventh-grade and eighth-grade children, demonstrating either mild-to-moderate dental fluorosis (fluorosis cases) or were fluorosis-free (fluorosis controls), 11 percent (N = 74) had lived in a fluoridated community for at least a year during their first six years of life. Forty percent of the fluorosis cases and 22 percent of the fluorosis controls were reported to have taken fluoride supplements during their residency in a fluoridated community, with 79 percent of the supplementation for both groups in the form of vitamins with fluoride. Further, these children had resided in more then twenty cities across ten states, and therefore do not represent just a localized problem. Such findings indicate that fluoride supplements had been incorrectly prescribed for a sizeable percentage of children residing in fluoridated areas; they also suggest an explanation for the recent increased prevalence of fluorosis in similar age-groups in some fluoridated areas. Given that the recent literature does not show that the appropriateness of supplemental prescription practices has improved for post-1975 birth cohorts, these findings suggest the need for enhanced professional education and monitoring to ensure that this occurs. PMID- 2212195 TI - Subjective signs of efficacious inferior alveolar nerve block in children. AB - This study is designed to examine the clinical signs relating to profound anesthesia of the primary dentition using the inferior alveolar nerve block (IANB) injection. The IANB injection has been used for many years for both adults and children to anesthetize the mandibular teeth. Most dentists are quite familiar with the signs of profound intraoral anesthesia in the adult. Because of infrequent exposure, they might not be as aware of the signs of adequate anesthesia on the child patient. Additionally, the dentist may not be able to differentiate apprehensive behavior from behavior elicited with inadequate pulpal anesthesia. The study consisted of forty male and female children. The subjects who ranged in age from 3 years to 12 years, with a mean age of 7 years, were scheduled for routine restorative care of mandibular primary teeth. Each subject was injected with 1.8 ml of 2 percent xylocaine, 1:100,000 epinephrine using the mandibular-block technique. Anesthesia was evaluated using direct ice placement, lip reaction, tongue reaction and gingival reaction at intervals of 0, 1, 2, and 5 minutes. The results showed a correlation of lip and tongue anesthesia and pulpal anesthesia over time. A stronger correlation existed with gingival anesthesia and pulpal anesthesia over time. There was no statistical relationship between the subject response to ice and pulpal anesthesia. PMID- 2212194 TI - Tongue skills and clearance of toffee in two age-groups and in children with problems of speech articulation. AB - If children use the same tongue skills in swallowing and clearing remnants of sticky foods from the mouth as they do in articulating during speech, it could then be hypothesized that those with impaired articulation might have poorer tongue skills and, consequently, slower rates of food clearance. Does age alter these skills and rates of clearance? Measurements were made of oral stereognosis, tongue-tip manipulation skill, control of tongue protrusion, and the time taken to chew and swallow a standardized piece of toffee and to clear it from the mouth. A statistically significant improvement in tongue skills with age was observed when results for twenty-three 19- to 23-year-old students were compared with those for twenty-nine 6 to 11-year-old children, but no distant differences in clearance rates were noted. Results for thirty-nine 5- to 8-year old children with impaired articulation and forty normal age-matched children showed the former group to have delayed chewing times and clearance rates, and poorer oral stereognosis and tongue protrusion control. Although these tests have shown significant differences between relatively large groups, the value of such tests on individuals is limited. PMID- 2212196 TI - Chlorhexidine as an oral hygiene adjunct for cyclosporine-induced gingival hyperplasia. AB - Recent advances in surgical technique and chemotherapeutic procedures have greatly increased the survival rates of organ transplantation patients. Of dental importance is the widespread use of the immunosuppressive agent cyclosporine in this special-patient population, a drug that has the potential to cause severe gingival hyperplasia as a side effect. A case is presented illustrating the use of the plaque-inhibitor chlorhexidine as a therapeutic adjunct in possibly arresting this gingival condition. PMID- 2212197 TI - Clinical and histologic findings of the dentition in a hypopituitary patient: report of case. AB - Idiopathic hypopituitarism is associated with delayed dental eruption as well as delayed growth of the dentofacial complex. Both maxillary and (especially) mandibular growth can be affected. The clinical dental findings and histologic findings related to enamel maturation in the permanent dentition of a teenaged male with a hypopituitary condition are described. PMID- 2212198 TI - Are minority children getting their fair share of dental services? AB - A review is provided of available national survey data on oral health of minority and nonminority children, and their use of dental services. Minority children continued to have greater need of dental care but use fewer dental health services, measured by a variety of methods, including the frequency and number of visits, and the types of services provided, such as preventive or restorative services. A smaller percentage of minority children had dental insurance coverage. Findings must continually be presented to legislators and finding agencies. PMID- 2212199 TI - Dose reduction in dental radiography. AB - All exposures to ionizing radiation for medical and dental purposes carry risks to both the patient and staff. It is now accepted practice that all exposures should be kept as low as reasonably practicable to minimize these risks. The various methods currently available for dose limitation in intraoral and panoramic radiography and their effects on image quality are considered. In intraoral radiography the use of fast (E-speed) film and rectangular collimation offer dose reductions of approximately 50 per cent and 60 per cent respectively. Constant potential X-ray units, longer focus-to-skin distances and rare-earth filtration will permit further dose reductions. In panoramic radiography the radiation dose to the patients can be reduced by up to one-eighth by combining the use of constant potential X-ray units, rare-earth intensifying screens and rare-earth filtration. PMID- 2212200 TI - Shortened dental arches and masticatory ability. AB - In a previous study concerning oral function with shortened dental arches, it was found that approximately 10 per cent of the patients investigated complained of impaired masticatory ability despite a substantial reduction in arch length and, as a consequence, food platform area. This finding differs from those of studies relating masticatory performance to food platform area. From a review of pertinent literature, it is concluded that impairment of masticatory ability is manifest when less than 10 occluding pairs of teeth are present. Shortened dental arches are not associated with shifts in food selection adversely affecting general health. PMID- 2212201 TI - Factors influencing the initiation of carious lesions in specific tooth surfaces over a 4-year period in children between the ages of 11-12 years and 15-16 years. AB - An analysis of factors influencing the initiation of carious lesions on specific tooth surfaces over a 4-year period in children between the ages of 11-12 years and 15-16 years is presented. Approximately 1000 children, resident in the County of South Glamorgan, Wales, were assessed for caries status and oral cleanliness in 1980 when aged 11-12 years and again in 1984 when aged 15-16 years. On both occasions, the children completed detailed questionnaires on dental health related topics. Surfaces which were sound when the children were 11-12 years were identified and subsequently awarded a score of zero if they remained sound at 15 16 years or a score of one if they had developed carious lesions or had been filled. For each child, a mean mouth caries initiation score was computed for specific groups of surfaces, namely pit and fissure surfaces in posterior teeth, approximal surfaces in posterior teeth, buccal and lingual smooth surfaces of all teeth and approximal surfaces of anterior teeth. One-way analysis of variance and multiple regression techniques revealed that a number of factors had a significant influence on the initiation of caries. The factors and their level of significance varied between the surfaces. However, relatively little (less than 6 per cent) of the total variance in caries initiation score could be explained by the identified factors. Overall, more lesions developed in pit and fissure surfaces in posterior teeth than in the other surfaces included in the analyses. PMID- 2212202 TI - Clasp retention and composites: an abrasion study. AB - An in vitro test for screening the abrasion resistance and abrasivity of composite resins when used to provide tooth undercuts for removable partial denture clasps is described. In the present study nine composite resins were tested against wrought stainless steel round clasps. The results indicated that the abrasion of any of the composites tested was unlikely to cause a noticeable loss of retention in the clinical situation. However, there was marked abrasion of the clasps by two of the composites which would be likely to be clinically relevant. PMID- 2212203 TI - In vitro marginal microleakage associated with five dentine bonding systems and associated composite restorations. AB - Fifty sound premolar teeth, extracted for orthodontic purposes and stored at room temperature in physiological saline since extraction, were prepared with a standardized minimal two-surface Class II cavity. The teeth were then ascribed randomly to five groups, each of ten teeth. Each of four groups was restored using a different dentine bonding system and the associated posterior composite resin according to the manufacturer's instructions. The fifth group was restored with Superbond C & B dentine bonding system and Occlusin composite. After immersion in de-ionized water for at least 7 days, the teeth were sealed with nail varnish to within 1 mm of the margin of the restoration. The teeth were then immersed in 5 per cent buffered Eosin for 48 h. Following mesiodistal sectioning the sections were photographed and subjected to image analysis to establish the length of dye penetration at the tooth/restoration interface and the amount of dye penetration into the crown dentine. Tripton/Occlusin and XR Bond/Herculite XR groups showed a significantly (P less than 0.05) smaller amount of leakage than Gluma/Lumifor or Scotchbond 2/P50 combinations when assessed as a percentage of the tooth/restoration interface exhibiting leakage. When the percentage of crown dentine showing dye penetration was considered, the Tripton/Occlusin group showed less leakage than the other material combinations. It is concluded that Tripton, when used with the recommended composite, will allow significantly less microleakage than Gluma/Lumifor, Scotchbond 2/P50 or Superbond C & B/Occlusin combinations and a similar amount to XR Bond/Herculite XR in vitro. PMID- 2212205 TI - Shovel-shaped incisors and associated invagination in some Asian and African populations. AB - Shovelling of the incisors is considered to be a polygenic inheritable trait. Shovelling differs considerably between groups of racial populations but is relatively stable within each group. Presence or absence of shovelling helps in racial identification and in exploration of ancestry. Periapical radiographs of patients of several nationalities from Asian and African continents were obtained. Shovelling and invaginations associated with the shovel-shaped incisors was studied according to nationality. Results indicated that the incidence of shovelling in Syrians, Jordanians, Palestinians and Filipinos was 5-6 per cent. In Saudi Arabians, Pakistanis and Indians, the incidence of shovelling was 10-12 per cent. Among Yemenis, Sudanese and Egyptians, the incidence of shovelling was 20-25 percent. The occurrence of invaginations in shovel-shaped incisors was 11 per cent. PMID- 2212204 TI - Fatigue and wear of dental materials. AB - Fatigue and wear are two of the many basic physical processes which contribute to the degradation of restorative materials. The mechanisms of these are discussed in the context of general engineering and the dental environment. More work is required to define the processes involved in intraoral degradation of materials. PMID- 2212206 TI - Influence of adrenaline on the onset time of lignocaine anaesthesia. AB - Rat sciatic nerves were employed to investigate the influence of adrenaline on the onset time for anaesthetic blockade induced by 2 per cent lignocaine HCl. The addition of adrenaline at three concentration levels to 2 per cent lignocaine HCl solutions delayed the onset time for conduction blockade. PMID- 2212207 TI - A light and scanning electron microscopic study of enamel decalcification in children living in a water-fluoridated area. AB - Eleven children, each having one or two pairs of premolars to be extracted for orthodontic purposes, participated in the study. The model involved placement of a special orthodontic band that allowed the accumulation of plaque in a defined area between the band and the buccal enamel. Examination of enamel changes was carried out in experimental teeth that had been exposed to local plaque accumulation for one, two, four, eight or 14 days. The specimens were examined under the light (LM) and the scanning electron microscope (SEM). All teeth had signs of very mild dental fluorosis. No indications of demineralization were noted after one day. SEM examination showed signs of crystal dissolution in some of the two-day specimens. Six of eight four-day specimens exhibited surface dissolution. All eight- and 14-day specimens showed signs of surface demineralization in the LM as well as in the SEM. These observations documented that undisturbed bacterial deposits are capable of initiating enamel demineralization within short time periods, even in children living in a water fluoridated area. PMID- 2212208 TI - Estimation by a 24-hour study of the daily dose of intra-oral mercury vapor inhaled after release from dental amalgam. AB - The difficulties associated with estimations of daily doses of inhaled mercury vapor released from dental amalgam are considerable. Existing data are often unreliable, especially if they are based on a single or a small series of samples of intra-oral concentrations of mercury vapor before, during, and after chewing stimulation. In the present paper, the aim was to obtain a more representative estimation of the daily dose of mercury vapor inhaled from amalgam fillings by measurement of amounts of mercury vapor released in the oral cavity during 24 h, under conditions that were as normal as possible. A series of measurements was carried out on each of 15 subjects, with at least nine occlusal surfaces restored with dental amalgam, and on five subjects without any amalgam restorations. The subjects had to follow a standardized schedule for 24 h, whereby they ate, drank, and brushed their teeth at pre-determined time periods. The amount of mercury vapor released per time unit was measured at intervals of 30-45 min by means of a measuring system based on atomic absorption spectrophotometry. None of the subjects was professionally exposed to mercury, and all of their amalgam fillings were more than one year old. Study casts were made for each subject, and the area of the amalgam surfaces was measured. Samples of urine and saliva were analyzed so that values for the mercury concentrations and the rate of release of mercury into saliva could be obtained. The average frequency of fish meals per month was noted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212209 TI - The effect of oxygen inhibition on an unfilled/filled composite system. AB - Oxygen is known to inhibit vinyl polymerization in resins used for restorative dentistry. This research examined the effects of unfilled resin being blown into a thin layer on etched bovine enamel in atmospheres of room air, argon, or a combination of the two. Onto this thin, cured resin surface, filled resin was added and cured under atmospheric conditions similar to those of the initial polymerization of the unfilled resin. Comparison of the effects of the different testing atmospheres was made by measurement of the shear bond strength of the resin/composite disc to the etched bovine enamel. Monomer conversion values of the unfilled resin were calculated from the infrared spectra of the simulated tooth/disc assembly. Blowing unfilled resin with compressed room air prior to curing caused poor monomer conversion values and resulted in low shear bond strength to etched enamel. Both high monomer conversion and shear strength values resulted when specimens were cured under all-argon conditions. A clinically practical method of maintenance of the tooth under a continuous stream of argon while being cured in room air was shown to provide greater monomer conversion than curing under room-air conditions alone. SEM evaluation showed that the inhibited layer present in room-air curing was both physically displaced by and absorbed into the overlying filled composite. Specimens cured in argon showed an intact, uniformly thick layer of bonding resin next to the etched enamel, with no displacement by or absorption into the composite addition. Unfilled resin cured in room air had a significantly greater thickness of polymerization-inhibited material than did resin cured in an argon atmosphere. PMID- 2212211 TI - Finite element analysis of the relationship between clasp dimensions and flexibility. AB - A parameter study with use of the finite element method was conducted for examination of the relationships between the shape parameters of a clasp (width and thickness at the base and tip of the clasp) and its displacement or stress. By synthesis of these relationships, a simple formula defining the clasp tip displacement in terms of clasp dimensions ("displacement formula") was obtained. A stiffness parameter "Fd" (the load producing a 1-mm displacement of the clasp tip) was proposed, and a formula defining Fd in terms of shape parameters was derived from the displacement formula. Fd would be a practical parameter for the definition of clasp retention, and the present formulae appear to be useful tools for investigation of the retention of removable partial dentures. PMID- 2212210 TI - Gradual increases in marginal leakage of resin composite restorations with thermal stress. AB - The effects of thermal stress on the marginal leakage of resin composite restorations in bovine teeth were investigated by a method that preserved the specimens. The changes in marginal leakage of specimens with increasing numbers of thermal cycles were measured by an electrical conductivity method. Four brands of posterior resin composites were used to fill cylindrical cavities (2.0 mm in diameter and 1.5 mm in depth) on the labial surfaces of bovine incisors, according to the manufacturer's instructions. Thermal cycling stress was applied to the specimens for up to about seven weeks (9000 cycles). During this time, the electrical conductance between the pulp and a drop of physiological saline solution covering the resin restoration was measured periodically by application of an electrical potential (60 Hz, 10 Vp-p). Thermal stress increased the marginal leakage gradually, rather than step-wise. Even before application of any thermal stress, wide variations of marginal leakage were found among different specimens restored with the same brand of resin. Specimens with less initial leakage showed less increase in leakage, and vice versa, throughout the experimental period. PMID- 2212212 TI - Formation of acellular root cementum in relation to dental and non-dental hard tissues in the rat. AB - After the periodontium of the rat was wounded, the formation of acellular extrinsic fiber cementum (AEFC) did not appear to be restricted to the hard dental tissues (pre-existing cementum, dentin, and enamel). Layers resembling AEFC were also deposited along the inner wall of the alveolar bone. At the time of observation (six weeks after being wounded), cells other than fibroblast-like cells could not be distinguished close to the newly formed AEFC-like layers. We suggest that the deposition of this material was related to the activity of periodontal ligament fibroblasts. PMID- 2212213 TI - Influence of chronic ethanol exposure on nitrous oxide analgesia in mice. AB - The purpose of this study was to determine whether sensitivity to nitrous oxide analgesia was altered by chronic ethanol exposure. Control mice exposed to 25%, 50%, and 75% nitrous oxide in oxygen demonstrated a concentration-related analgesic effect, as measured by the acetic acid abdominal constriction test. Other mice previously exposed to ethanol vapors for 72 h exhibited a significantly reduced sensitivity to nitrous oxide analgesia. The dose-response curve of the chronic ethanol-exposed group was shifted to the right of that of the control mice. These findings suggest the possibility that subjects with a history of alcohol abuse might have reduced responsiveness to nitrous oxide in a clinical setting. PMID- 2212214 TI - Electromyographic heterogeneity in the human temporalis muscle. AB - This study examined the possible existence of regional differences in activation of the temporalis muscle. Since the muscle is fan-shaped, its fibers pull in different directions. This suggests regional specialization for different motor tasks. EMG activity was registered by six bipolar fine-wire electrodes inserted anteroposteriorly across the muscle belly. Muscle signals were recorded during different static bite tasks for which both the direction and magnitude of bite force were specified. The results showed that the ratio of activities of the six muscle regions changed with the direction of bite force. This indicates a partitioning of the excitatory command to the muscle's motoneuron pool. Alteration in activity with changing bite-force direction was generally the smallest in the anterior-most region of the muscle, the largest in the posterior most region, and the intermediate in the interjacent regions. Generally, all muscle regions exhibited the highest EMG activity when the bite force was in an approximately posterolateral direction. The muscle was activated uniformly only for bites in this preferential direction. Activity in the regions appeared to be scaled up or down in a linear way according to the desired bite-force level. The results indicate that the direction of pull of the muscle and the maximal force it can produce are not fixed, but depend on the direction of bite force. PMID- 2212215 TI - Bacteremia in children following dental extraction. AB - The incidence and intensity of bacteremia following tooth extraction in children were measured by blood culture. The effects on bacteremia of the number and type of teeth extracted, oral hygiene, gingival health, presence of abscess, and antibiotic prophylaxis were assessed. Antibiotic prophylaxis reduced the incidence of bacteremia from 63% to 35%. The intensity of bacteremia was 2 cfu/mL of blood or less in 80% of the children. An agar pour-plate method of blood culture was significantly more effective than broth in culturing the small volumes of inoculum. Of 83 bacterial strains characterized, 39 were strict anaerobes or micro-aerophilic, and the remainder mainly streptococci. S. mitior and S. sanguis were most commonly isolated, often in pure culture, and were generally sensitive to antibiotics. No direct association was demonstrated between the plaque and gingival indices and incidence of bacteremia or between the number of teeth extracted and the incidence or intensity of bacteremia. It is concluded that all children at risk from infective endocarditis require antibiotic prophylaxis prior to tooth extraction, since it is impossible for the likelihood or intensity of transient bacteremia to be clinically predicted. PMID- 2212216 TI - The utility of the BANA test for monitoring anaerobic infections due to spirochetes (Treponema denticola) in periodontal disease. AB - Treponema denticola, Porphyromonas gingivalis, and Bacteroides forsythus each possesses an enzyme(s) that hydrolyzes the synthetic substrate benzoyl-DL arginine-naphthylamide (BANA). The presence of these organisms in a subgingival plaque sample can be determined by the ability of the plaque to hydrolyze BANA. In the present study, we describe the usefulness of the BANA test at various stages of a clinical trial of the efficacy of metronidazole in the treatment of periodontal disease. A BANA-positive test was significantly associated with high levels and proportions of spirochetes in the plaque, so that it provided information comparable with that which could be obtained by a microscopic examination of the plaque. Patients with such anaerobic spirochetal infections were randomly assigned to a group receiving either metronidazole or placebo (250 mg, three times a day) for one week and whose teeth were scaled and root-planed. The advantages of the decision that metronidazole be used were apparent from the comparison with the results obtained in the patients who received only the scaling and root planing. The initially BANA-positive teeth in the patients treated with metronidazole, scaling, and root planing gained attachment and exhibited a significant reduction in the need for periodontal surgery, when compared with the BANA-positive teeth in the patients who received only placebo, scaling, and root planing. After the conclusion of this therapy, those teeth with persistent BANA-positive plaques had significantly higher proportions and levels of spirochetes than did the teeth with BANA-negative plaques.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212217 TI - The animal rights war on biomedical research: a call to arms. PMID- 2212218 TI - A brief history of the AADS Information Technology Committee. PMID- 2212219 TI - The AADS strategic plan for dental informatics. PMID- 2212220 TI - Patient simulation consortium. PMID- 2212221 TI - Decision support and the beginnings of a consortium. PMID- 2212222 TI - Consortium on multi-media information technology to enrich dentistry--COMMITTED. PMID- 2212223 TI - The developing electronic curriculum consortium. PMID- 2212224 TI - The national and international dimensions of dental informatics. PMID- 2212225 TI - Dental informatics: strategic issues for the dental profession. PMID- 2212226 TI - Trends in dental hygiene applicant pool size and characteristics of students upon entry over three decades. AB - A survey was conducted to determine trends that have occurred in the dental hygiene applicant pool and characteristics of entering dental hygiene students between 1957 and 1987. A two page, 46-item questionnaire with a cover letter and stamped pre-addressed envelope was mailed to each dental hygiene program director in the United States. A second mailing was sent one month later to directors who had not responded to the first mailing. A total of 106 usable questionnaires were returned, for a 54 percent response rate for 1987 programs. Response rates for programs existing in 1977, 1967, and 1957 were 51 percent, 45 percent, and 45 percent, respectively. For associate degree/certificate and baccalaureate degree programs, results suggest trends toward (1) a dramatic decline in dental hygiene applicants over the past ten years, (2) a decrease in dental hygiene class size, (3) an increase in age of applicants and length of education prior to acceptance into dental hygiene programs, and (4) a slight decrease in applicants' overall grade point average and science grade point average in the past decade. In addition, findings indicate that dental hygiene remains predominantly a Caucasian woman's profession. Implications of these findings for recruitment efforts and the numbers of dental hygienists for the future are discussed. PMID- 2212227 TI - The transfer effect of leadup activities. AB - Previous literature shows that operative laboratory performance can be significantly improved through leadup training where students complete simulated preparations in plastic blocks. Since the task requirements of most fixed prosthodontic preparations seem similar to those of operative dentistry, it may be hypothesized that leadup training utilizing operative-like preparations would facilitate performance in the projects of both courses. The objective of this study was to test that hypothesis. The performance of students who had completed the leadup training nine months earlier was compared with that of randomly selected control groups, with replacement, in a subsequent operative and fixed prosthodontics course. Calibrated raters were unaware of group affiliation of products. Analyses of variance showed that students in the experimental group statistically significantly outperformed those in the control group on the two operative preparations which were most like products completed during the leadup training. There was no such difference for any of the three fixed prosthodontics products. It is concluded that transfer of training is highly specific and that leadup training must simulate the criterion in both its cognitive and motor components, if it is to have a facilitating effect. PMID- 2212228 TI - Expert opinions on nutrition issues in clinical dentistry. AB - Diet assessment and counseling are essential components of comprehensive preventive dental care programs. However, the lack of consensus on what constitutes appropriate nutrition services has resulted in diversity in the level and quality of such services to dental patients. Seventy nine nationally recognized experts in dental nutrition were surveyed using the Delphi method to seek consensus on the appropriate scope of nutrition in clinical dentistry. PMID- 2212229 TI - Self perceptions of skill in office medical emergencies. PMID- 2212230 TI - Peer evaluation of teaching effectiveness. PMID- 2212231 TI - Implications of gene amplification for evolution and management of insecticide resistance. AB - Simulations were used to compare evolution of insecticide resistance predicted by a conventional two-allele model with predictions from three- and four-allele models that assume resistance is based on gene amplification. Results were similar between models when insecticide concentration was low or moderate. In contrast, when 10% of the population was not exposed to insecticide each generation, high insecticide concentrations slowed resistance development in the two-allele model, but caused rapid development of high levels of resistance in the three- and four-allele models. The presence of a third allele at an initial frequency as low as 10-7 doubled or tripled the rate of resistance development in some cases. Attempts to slow evolution of resistance by overwhelming it with high concentrations of insecticides are not likely to succeed if gene amplification or other mechanisms generate alleles that confer high levels of resistance. PMID- 2212232 TI - Evolution of pesticide resistance: interactions between generation time and genetic, ecological, and operational factors. AB - We used computer simulation modeling to clarify the relationship between generation time and the rate of evolution of pesticide resistance. We examined the influence of generation time under various assumptions about genetics, population dynamics and selection pressures. The simplest model demonstrated that the time required for resistance to evolve can be independent of generation time. However, interactions of generation time with genetic, biological and operational factors resulted in positive, negative, and U-shaped relationships between the number of generations per year and the time required for resistance to evolve. These results preclude any generalizations concerning the influence of generation time on resistance evolution. Some ability to predict the influence of generation time may still exist on a case-by-case basis if the context of the resistance episode can be specified. PMID- 2212233 TI - Efficacy of abamectin fed to German cockroaches (Dictyoptera: Blattellidae) resistant to pyrethroids. AB - Ten field-collected strains of the German cockroach, Blattella germanica (L.), with varying levels of pyrethroid resistance were tested for possible cross resistance to abamectin administered as a bait. The time-mortality method was used for comparison of response with a known susceptible strain in 10-d feeding experiments. Essentially no resistance to abamectin was found. Extensive feeding inhibition occurred after a few days, but the amount of abamectin consumed varied substantially from strain to strain. Abamectin may have considerable potential as a cockroach bait insecticide. PMID- 2212234 TI - Toxicity, sublethal effects, and performance of sulfluramid against the German cockroach (Dictyoptera: Blattellidae). AB - Topical and oral toxicity of sulfluramid (N-ethyl perfluorooctane sulfonamide) were determined for the German cockroach, Blattella germanica (L.). The topical LD50 of sulfluramid was 175.6 micrograms/g for adult males, 117.8 micrograms/g for adult females, and 122.3 micrograms/g for gravid adult females. Ingestion increased toxicity approximately 1.4 times for adult male B. germanica. Twenty four hours after topical treatment with 20 micrograms/insect sulfluramid, the percentage of female cockroaches that dropped their oothecae increased approximately 50% compared with controls treated with acetone. Sulfluramid also decreased oothecal hatch of both dropped and retained oothecae. Approximately 90% of oothecae from untreated females hatches, whereas less than 20% hatched from females treated with 20 micrograms/insect. Mean time for oothecal hatch increased linearly with increasing sulfluramid concentration. In arena studies in Ebeling choice boxes, LT50's ranged between approximately 2.3 and 3.9 d for a 0.331 mg/cm2 deposit and a 1.5% bait, respectively. Higher concentrations of sulfluramid were more repellent in both bait and residual formulations. Performance index values indicated excellent potential field efficacy. Field trials with 1.0 and 1.5% (AI) baits showed up to a 71.3% reduction in cockroach numbers. Baits controlled cockroaches throughout the 12-wk test. PMID- 2212235 TI - Morphogenetic effects of hydroprene on genitalia of the oriental cockroach (Dictyoptera: Blattidae). AB - Hydroprene had a considerable effect on the morphogenesis of external genitalia of the oriental cockroach, Blatta orientalis L. Exposure of nymphs to hydroprene resulted in abnormal adultoids with structural and positional distortions, and reduced or absent cuticular sclerotizations of the external genitalia. Late nymphal instars were significantly more sensitive to hydroprene than were early instars. In males, the epithelial cells of wings, serrata of the right phallomere, titillator and other lobes of the left phallomere were sensitive to hydroprene. The left phallomere was often prolapsed, distorted, and reduced in sclerotization. The right phallomere, particularly the serrata, was extremely malformed. In severe cases, phallomeres were entirely distorted or fused to each other. In females, the overall structure of the ovipositor appeared flaccid, less sclerotized, and misshapen. The first and second pairs of valvulae were often misshapen and reduced in sclerotization and length, or even fused with the third valvulae. This study provides morphological evidence that B. orientalis with malformed genitalia after treatment with hydroprene would be unsuccessful in copulation and fertilization. A high correlation between wrinkled wings and malformed male genitalia can be an important criterion to evaluate the effects of hydroprene on this species. PMID- 2212236 TI - Age distribution of adult female screwworms (Diptera: Calliphoridae) captured on sentinel animals in the coastal lowlands of Guatemala. AB - The age structure of screwworm, Cochliomyia hominivorax (Coquerel), populations was studied in the Guatemalan lowlands with the pteridine technique of age determination. Flies (95% were 4-15 d old) were captured on sentinel animals. Mean age was 7.5 d. The oldest fly captured was 21 d old. Most flies visiting wounds were reproductively mature females. Of these, about one-half oviposited once, one-third oviposited twice, and 1 in 10 completed three ovarian cycles (assuming a 3-d interval between clutches). Periodicity in adult capture rates may be related to the reproductive cycle. Results suggest that local populations are composed of a high proportion of synchronized cohorts. PMID- 2212237 TI - The Morgan Recharger: a new horn fly (Diptera: Muscidae) control device for beef cattle. AB - A 20% diazinon formulation was evaluated for control efficacy against the horn fly, Haematobia irritans (L.), in the Morgan Recharger (Morgan International Products, College Grove, Tenn.). The Morgan Recharger releases insecticide with a wicking system from an insecticide reservoir and can be attached to an animal's ear or tail. This device was most effective against the horn fly when used as an ear tag with two per head; horn fly counts did not exceed five flies per side through 8 wk. The diazinon formulation tested was released from the Morgan Recharger at a decreasing rate. The problems and potential of the Morgan Recharger as an effective horn fly control device are discussed. PMID- 2212238 TI - Cattle lice (Anoplura, Mallophaga) in New York: seasonal population changes, effects of housing type on infestations of calves, and sampling efficiency. AB - A year-long survey was made of commercial dairy herds in New York for cattle lice (Anoplura and Mallophaga). All herds were infested with lice. The cattle bitting louse, Bovicola bovis (L.), accounted for about 90% of the observed infestations; infestations of mature animals were most common during the winter months, especially March (26% infested); and infestation rates of calves were high (30 45%) from January through June. Cows that were housed in stanchion barns were about twice as likely to be infested (24.7%) as were those in free stalls (11.1%). Calves housed in individual outdoor hutches had substantially lower infestation rates (4.5%) than calves maintained inside barns in collective stalls and pens (46.0%). PMID- 2212239 TI - Pruritus and behavior of pigs infested by itch mites, Sarcoptes scabiei (Acari: Sarcoptidae). AB - Effects of infestation by Sarcoptes scabiei (De Geer) on pruritus and other behaviors of pigs for 9-13 wks after weaning were evaluated. Regardless of the dose of mites inoculated, pigs fed ad lib. spent approximately 60% of their time at rest. Within their average day, pigs spent more time eating in morning and evening, were more active and pruritic at midday, and rested more and spent the least time drinking water at night. Mite infestations increased total activity and time spent scratching and rubbing. Infested pigs sprayed with water rubbed and scratched 4-10 times more frequently than those left undisturbed or disturbed by other means. Pigs receiving inoculating doses of 1,000 mites became more pruritic than pigs receiving 100 mites, and both groups developed more pruritus than non-infested control pigs. PMID- 2212240 TI - Effects of horn fly and house fly (Diptera: Muscidae) larvae on the development of parasitic nematodes in bovine dung. AB - Laboratory studies were conducted to determine the effects of horn fly, Haematobia irritans (L.), and house fly, Musca domestica L., larvae on the development of a mixed population of parasitic nematodes in compressed and crumbled bovine dung. Fresh dung (100 g per sample) from a single calf passing trichostrongyle type eggs was infested with 150 horn fly or 150 house fly eggs. After 14-15 d, more horn flies and house flies had emerged from the compressed dung than from the crumbled dung, but more third stage parasitic nematode larvae were recovered from the crumbled dung containing either fly species than from dung containing no flies. PMID- 2212241 TI - President's message. Address to all ET nurses: the state of the specialty. PMID- 2212242 TI - Prevalence of pressure ulcers in five patient care settings. PMID- 2212243 TI - Impaired skin integrity related to radiation therapy. AB - Skin reactions associated with radiation therapy require frequent nursing assessment and intervention. Preventive interventions and early management can minimize the severity of the skin reaction. With the understanding of the pathogenesis of radiation skin reactions, the ET nurse can determine who is at risk and then implement preventive measures. Because radiation treatment is fractionated, skin reactions do not usually occur until midway through the course of therapy and will subside within a few weeks after completion of radiation. Many patients and their families still fear that radiation causes severe burns. Teaching and anticipatory guidance by the ET nurse is needed to assist patients and their families to overcome this fear, and to educate them on preventive skin care regimens. PMID- 2212244 TI - Sharing resources for clinical research. AB - The unstructured, verbal contact of the Sharing Resources Model between persons of different institutions allowed each to accomplish goals. In a time of limited health care funding, this model helped all involved to conduct nursing research. The director and ET nurse explored long-term questions about research. For example, during this time of nursing shortage, how does a nurse researcher include the staff nurse in clinical research? How can clinical agencies implement research findings and monitor their impact? Can research interest of the nursing staff be stimulated by reading research? In addition these individuals were able to document a need for continued research development and research consultation. Sharing of resources allowed the nurse faculty member to be a team member in the agencies in which she was conducting research. Providing consulting allowed her to repay to the agencies the time commitment they made to her research and an opportunity to share with clinical experts. Clinical agencies and schools of nursing need to examine ways to increase research collaboration. Since ET nurses are exposed to numerous researchable questions, they should explore within their agencies the structuring of nursing research. If nursing research assistance is not available, the Sharing Resources Model may initially help ET nurses with their research and document a need to the agency for research assistance. Whatever model the ET nurse uses for research assistance, all involved should benefit. PMID- 2212246 TI - A study of interface pressure for pressure reduction and relief mattresses. PMID- 2212245 TI - Toxic epidermal necrolysis: recognition and treatment. PMID- 2212249 TI - Ambient temperature and postoperative catabolism. PMID- 2212248 TI - Implementation of the ET nurses' role. PMID- 2212247 TI - Leg ulcers. PMID- 2212250 TI - Raised intraabdominal pressure, renal failure, and the bumble bee. PMID- 2212251 TI - Nitrogen sparing and the catabolic hormones in patients nursed at an elevated ambient temperature following major surgery. AB - Fasted patients managed at an elevated ambient temperature following major surgery have reduced nitrogen excretion and body protein catabolism. To investigate the mechanism behind this three 24 h urine collections were made in 16 patients nursed for 48 h following aortobifemoral surgery on a Clinitron fluidized bed at 32 degrees C and analysed for total urinary nitrogen, cortisol and catecholamine excretion. Results were compared with a similar group of patients nursed throughout on a standard ITU bed at 22 degrees C. Patients managed at the elevated ambient temperature showed a significant reduction in the cumulative total urinary nitrogen (20.73 g +/- 6.42 v 28.95 g +/- 6.44; mean +/- S.D.; p less than 0.002) and cortisol excretion (1238 microg +/- 436 v 2197 microg +/- 844; mean +/- S.D.; p less than 0.001). Catecholamine excretion was also reduced but failed to achieve significance. There were significant correlations between cumulative total nitrogen excretion and both cortisol (r = +0.414; p = 0.02; n = 32) and noradrenaline (r = +0.369; p = 0.05; n = 32). These results confirm that the beneficial effect of an elevated ambient temperature on postoperative protein metabolism is brought about through a reduction in metabolic stress. PMID- 2212253 TI - Selective positive end-expiratory pressure and cardiac function in dogs. AB - Effects of general (G) versus selective (S) right (R) and left (L) positive end expiratory pressure (PEEP) were compared during differential lung ventilation in 11 anaesthetized dogs in the supine position. GPEEP 20 cmH2O decreased cardiac output (1 min-1) from 2.9 +/- 0.2 (mean +/- SE) to 1.7 +/- 0.5 (p less than 0.05), RPEEP from 2.8 +/- 0.2 to 2.2 +/- 0.2 (p less than 0.05) while LPEEP caused no significant change in cardiac output. GPEEP increased pleural pressure more than SPEEP. Pleural pressure was asymmetric during SPEEP. Both SPEEP and GPEEP increased pericardial pressure uniformly, but the increase was less marked with SPEEP. During GPEEP 20 cmH2O transmural left ventricular end-diastolic pressure (LVEDP) decreased markedly. SPEEP caused less marked reductions in transmural LVEDP. Qualitatively similar, but less marked changes were observed with PEEP 10 cmH2O. In conclusion, cardiac output decreased less with selective PEEP than with general PEEP. This was explained by less increase in pleural and pericardial pressure, and accordingly less decrease in LV transmural filling pressure. PMID- 2212252 TI - Is intensive care justified for patients with haematological malignancies? AB - The course of 260 adults with haematological malignancies admitted to a medical intensive care unit was studied to evaluate the value of life support techniques and to research predictive factors. The overall in the medical intensive care unit (MICU) and hospital mortality rates were respectively 43% (113 patients) and 57% (148 patients). Among survivors, 64% (49 patients) were still alive after 6 months and 44% (35 patients) after 1 year. Among 34 haemodialysed patients, the MICU mortality was 67% (23 patients) and among 111 mechanically ventilated patients 85% (94 patients). Prolonged mechanical ventilation, more than seven days, was performed in 11 of the 17 survivors and did not influence long term survival. No individual predictor of mortality was found comparing survivors and non-survivors. However, SAPS, intractable sepsis and failure of more than one organ system were significantly different in non-survivors (p less than 0.001). Among the 20 patients requiring both mechanical ventilation and haemodialysis, only two left the MICU and both died soon thereafter. We conclude that life support therapy should be initiated in patients with haematological disorders and that prolonged mechanical ventilation is compatible with long term survival. However, the combination of mechanical ventilation and haemodialysis is always associated with a poor prognosis and therefore the use of both techniques simultaneously for one patient is questionable. PMID- 2212255 TI - Intestinal decontamination in a polyvalent ICU. A double-blind study. AB - A double blind, placebo-controlled trial was performed to test the efficacy of prevention of nosocomial infections by selective digestive decontamination. Placebo or tobramycin (80 mg) and colistin (100 mg) was given four times daily via the gastric tube. Amphotericin B (500 mg/6 h) was administered to all patients. As our ICU is divided into two separate subunits, intestinal decontamination or placebo was administered alternatively to patients of the two subunits during two 3-month periods, separated by a 2-month period without prevention. The decontamination (n = 97) and placebo groups (n = 84) were similar with respect to age, sex, severity score and diagnostic categories on admission. Intestinal decontamination alone failed to significantly reduce the number of infected patients (26% vs 34.5%, p = 0.20), but was effective on ICU-acquired infections (0.33 vs 0.60, p = 0.02) especially gram-negative infection rates (0.17 vs 0.43, p = 0.01). The onset of the first ICU-acquired infection was delayed (9 vs 13 days, p less than 0.001) and incidence of pneumonia (2 vs 13 cases, p less than 0.01) including bacterial pneumonia (0 vs 8 cases, p less than 0.01) was significantly decreased. However, mean ICU stay and mortality were not significantly modified by intestinal decontamination. PMID- 2212256 TI - The use of midazolam versus propofol for short-term sedation following coronary artery bypass grafting. AB - Midazolam and propofol were compared in an open randomized study for postoperative sedation during 12 h of mechanical ventilation in 40 patients following coronary artery bypass grafting. After an intravenous loading dose of midazolam (50 micrograms.kg-1) or propofol (500 micrograms.kg-1), a titrated continuous infusion was administered of midazolam (mean dose 38.1 micrograms.kg 1.h-1 (SEM 2.6)) or propofol (mean dose 909 micrograms.kg-1.h-1 (SEM 100)) together with a narcotic analgesic infusion. During mechanical ventilation midazolam and propofol produced a similar quality of sedation, but recovery (midazolam 66 min (SEM 16); propofol 24 min (SEM 7)) and weaning from the ventilator (midazolam 243 min (SEM 44); propofol 154 min (SEM 33)) where faster with propofol. In the 2 groups administration of an intravenous loading dose caused a significant decrease in mean arterial pressure but hemodynamic tolerance during maintenance infusion was good. PMID- 2212254 TI - Gentamicin volume of distribution in critically ill septic patients. AB - Gentamicin intrapatient pharmacokinetics variations were studied in 40 critically ill medical patients, suffering gram-negative sepsis. These patients were studied in two phases throughout gentamicin treatment: firstly, on the second day of treatment, when aggressive fluid therapy was required, and secondly, five days later, when patients had achieved a more stable clinical condition. Pharmacokinetic parameters were determined using least squares linear regression analysis assuming a one-compartment model using the Sawchuk-Zaske method. The apparent volume of distribution (Vd) in the first phase of the study was 0.43 +/- 0.12 L/kg, while on the seventh day of treatment it was 0.29 +/- 0.17 L/kg (p less than 0.001). Statistically significant differences were also observed for peak serum concentration (p less than 0.001), total dosage recommended (p less than 0.001) and half-life (p less than 0.05), whilst differences were not found for trough levels. From the analysis of the results obtained, we recommend increasing the initial dosage and monitoring plasma levels within the first days of therapy in critically ill patients treated with gentamicin, since important variations in aminoglycoside Vd related to disease, fluid balance and renal function, commonly occur in these patients. PMID- 2212257 TI - A comparison of measurements of blood pressure, heart-rate and oxygenation during inter-hospital transport of the critically ill. AB - Critically ill patients transferred between hospitals are often inadequately monitored in transit, with outcome adversely affected. In 22 such patients, we compared direct and palpated measurements of systolic pressure, oscilloscopic and aneroid manometric measurements of mean pressure, ECG and palpated measurements of heart-rate and clinical and oximetric assessments of oxygenation. On average palpated readings of systolic pressure under-read direct readings by 29% and palpated readings of heart-rate under-read ECG readings by 2%. The mean difference between oscilloscopic and manometric readings of mean pressure was zero. Oxygen saturation readings did not reach a level which allowed valid comparison. If direct measurement of heart-rate and blood pressure by battery powered monitors is not feasible, palpation of heart-rate and manometric measurement of mean arterial pressure are acceptable alternatives during secondary transport of the critically ill. PMID- 2212258 TI - Does the stress of admission to an intensive care unit influence arginine vasopressin secretion and renal diluting ability? AB - The pathogenesis of excessive arginine vasopressin (AVP) release and hyponatraemia in euvolaemic intensive care unit (ICU) patients is poorly understood. Stress has frequently been proposed as a possible determinant, but its actual responsibility has not been adequately assessed. Therefore, water-load tests were prospectively performed in 11 patients admitted to the ICU for severe or potentially severe diseases, but who had no other condition which could result in excessive AVP release or impairment of renal diluting ability. Renal diluting ability was normal in 9 patients. Two patients exhibited very slight defects, which might be the consequence of subclinical haemodynamic alterations, since one had a pulmonary embolism and the other manifested a gastrointestinal haemorrhage just after the completion of the water load. Nevertheless, plasma AVP levels decreased in response to the water load in all the patients, resulting in a significant decrease in mean values. Plasma norepinephrine values were found to be elevated both before and after water loading. A highly significant correlation existed between the levels of norepinephrine and those of AVP measured before the load, but was lost after it. In addition, norepinephrine values were markedly elevated in two patients who exhibited strictly normal renal diluting abilities, and no correlation was found between plasma norepinephrine values and any parameter of renal water excretion. Our study shows that the stress of a serious illness and of admission to an ICU does not seem to interfere, by itself, with osmotic regulation of AVP secretion and renal diluting ability, and that sympathetic activation is not, under such circumstances, a predominant stimulus for AVP release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212259 TI - Impaired renal function due to raised intraabdominal pressure. AB - A 19-year-old male developed renal failure after a laparotomy for liver trauma (urinary output of 30 ml/h, plasma creatinine 220 mumol/l). Surgical decompression of the abdomen was performed without any attempt at correcting the underlying pathology. This reduced the intraabdominal pressure (IAP) from 40 to 24 cm H2O and resulted in a massive diuresis (530 ml/h). Twenty-four hours later the plasma creatinine peaked at 280 mumol/l and then returned to within the normal range. This case report confirms that there is a direct relationship between IAP and renal function. PMID- 2212260 TI - Continuous arteriovenous haemodialysis during emergency hepatic retransplantation: two case reports. AB - Two patients with severe hepatic and renal failure underwent emergency hepatic retransplantation (2nd and 6th day after transplantation). Continuous arteriovenous haemodialysis was begun before surgery and successfully performed, without any incident, during the retransplantation with a biospal (SCU/CAVH AN 69 S) device, without pump. Vascular access was obtained with femoral catheters. Such a continuous dialysis and ultrafiltration allowed us to infuse massive amounts of blood products before and during surgery and to maintain pH, potassium and lactate at levels compatible with survival in anuric patients. Standard haemodialysis replaced CAVHD when haemodynamic stability was restored. PMID- 2212261 TI - Capillary leakage complicated by compartment syndrome necessitating surgery. AB - A single episode of systemic capillary leak syndrome is reported in a HIV positive patient. The shock had necessitated the infusion of large amounts of fluid with concomitant diffuse swelling and weight gain leading to compartment syndrome of both legs. This required surgical relief. The initial high hematocrit (62%) and low serum protein concentration (48 g/l) with normal factor V (molecular weight above 300,000) concentrations are the hallmark of capillary leak when they are associated with hypovolemic shock. It must be emphasized that fluid resuscitation may worsen the muscle damage with ultimate compartment syndrome. Therefore, it appears reasonable to monitor muscular pressure during volume expansion in patients with capillary leak syndrome, severe shock and muscular swelling. PMID- 2212262 TI - White clot syndrome and continuous arteriovenous haemofiltration. AB - Severe heparin associated thrombocytopenia is a rare complication of heparin therapy. We report a patient who developed heparin associated thrombocytopenia during continuous arteriovenous haemofiltration and discuss its implications and alternative anticoagulant treatment. PMID- 2212263 TI - Survival in adults after cardiac arrest due to drowning. AB - Some remarkable cases of full neurological recovery after cardiac arrest following immersion incidents have been intermittently reported in the journals over the years. These have largely been in children or teenagers who have fallen into extremely cold water. We report here two older adults who recovered completely after a period of cardiac arrest in cold water. Certainly, death should not be pronounced in cold water drowning, without a thermometer reading and ECG. PMID- 2212264 TI - Naloxone administration and laryngospasm followed by pulmonary edema. AB - A 50-year-old woman underwent laryngoscopy. Postoperatively she received naloxone and was extubated. She developed severe laryngospasm and one hour later pulmonary edema. Both naloxone administration and laryngospasm can provoke pulmonary edema; the pathophysiology is discussed. It is suggested that naloxone is administered with care to patients who in the preceding hours have had severe laryngospasm. PMID- 2212265 TI - Rewarming by extracorporeal circulation. PMID- 2212266 TI - Intrapleural placement of minitracheostomy--egress of air after insertion does not guarantee correct placement. PMID- 2212267 TI - Early treatment of mild tetanus with dantrolene. PMID- 2212268 TI - Gastric pH control and pneumonia in the critically ill. PMID- 2212270 TI - Facilitation of word recognition by semantic priming in schizophrenia. AB - Schizophrenic (n = 21), bipolar (n = 18), and normal control subjects (n = 21) were compared on a word recognition measure of semantic priming. The task involved the presentation of related, neutral, and unrelated word pairs; the second word (target word) in each pair was presented in a degraded form. Facilitation was defined as the accuracy of target word recognition for the related word pairs minus accuracy for the neutral word pairs. Titration, achieved by manipulating the degradation of the target word, was used to maintain each subject's overall accuracy for related and neutral items at approximately 50%. This procedure minimized the artifactual effects of overall accuracy on the difference score. Schizophrenics exceeded both normal control subjects and bipolar subjects on facilitation. Bipolar subjects did not differ from control subjects. The results support Maher's hypothesis that semantic priming effects are heightened in schizophrenia. PMID- 2212269 TI - More on gastric colonization, H2 antagonists or antacids. PMID- 2212271 TI - Hypnotizability, preference for an imagic cognitive style, and memory creation in hypnosis. AB - We sought to extend the finding (Laurence & Perry, 1983) that it is possible through hypnosis to create a pseudomemory of a specific event. Subjects were compared on their responses to a hypnotic suggestion. We also examined the relation between nonhypnotic measures (Preference for an Imagic Cognitive Style [PICS] test and the Tellegen Absorption Scale [TAS]) and response to the suggestion. Highly (45.45%) and moderately-highly (46.15%) susceptible subjects believed that the pseudomemory was veridical, but none of the low susceptible subjects did so. Together, hypnotic susceptibility, the PICS, and their interaction more strongly predicted pseudomemory creation than any of these main effects alone. Performance on the TAS was also related to the occurrence of pseudomemory, but this relation was redundant with performance on the other measures. These results point to the complexity of the variables involved in pseudomemory creation during hypnosis. PMID- 2212272 TI - Marital interaction and depression. AB - In this article, patterns of marital interaction as a function of depression and marital satisfaction are examined. The purpose of the study was to separate dysfunctional marital interaction patterns that were unique to depression from those that were associated with marital distress. The presence or absence of a depressed wife was crossed with level of marital satisfaction (distressed or nondistressed) to produce four groups of subject couples. Couples in which the wife was depressed exhibited more depressive behavior than did nondepressed couples, but only during discussion of a high conflict (as opposed to neutral) topic. Sex X Depression Level X Marital Satisfaction interactions were found for aggressive behavior: Depressed women in nondistressed relationships exhibited behavior that was characteristic of maritally distressed couples (high rates of aggression). In contrast, the husbands of these women exhibited behavior that one would expect in happily married couples (low rates of aggression). We failed to replicate previous findings that depressive behavior served a coercive function, although distressed couples, regardless of depression status, exhibited all the usual signs of negative dysfunctional interaction. In general, the findings suggested that marital distress rather than depression per se may be responsible for the dysfunctional interaction patterns frequently observed in depressed couples. PMID- 2212273 TI - Endorsement of dysfunctional beliefs depends on current mood state. AB - In two studies we tested the hypothesis that endorsement of dysfunctional beliefs depends on current mood state for persons who are vulnerable to depression. The first study showed that reports of dysfunctional beliefs vary with spontaneous diurnal mood fluctuations in 47 depressed psychiatric patients. The effect of mood state was highly significant (p less than .01); dysfunctional thinking increased when mood was worst and decreased when mood was best. The second study conceptually replicated this finding in a population of asymptomatic subjects. As predicted, reports of dysfunctional beliefs varied as a function of mood state in 14 persons who had experienced a depressive episode but not in 27 who had never been depressed. These findings support the cognitive theory of depression, which proposes that dysfunctional beliefs are vulnerability factors for depression but also that reporting of dysfunctional beliefs depends on current mood state. PMID- 2212275 TI - Evaluating the construct validity of psychopathy in black and white male inmates: three preliminary studies. AB - Although Black inmates represent almost half the population of United States prisons and have been included in several studies of psychopathy, there appear to be no published studies to date addressing the validity of the psychopathy construct in Black inmates. Three studies were conducted to assess the validity of the construct in Black male inmates using Hare's Psychopathy Checklist (PCL). In Study 1, we examined the internal structure of the PCL and the relation of checklist scores to several constructs relevant to psychopathy. We observed differences between Blacks and Whites in the distribution of psychopathy scores, in the relation of psychopathy to measures of impulsivity, and in the congruence of the underlying factor structure of the PCL. In Study 2, Black psychopaths were found to manifest a pattern of passive avoidance deficits similar but not identical to that reported for White psychopaths in Newman and Kosson's study. Study 3 demonstrated that psychopaths of both races receive more criminal charges in a wider variety of offense categories than do nonpsychopaths. The psychopathy construct appears tentatively applicable to Blacks, although its components may be somewhat different than for Whites. PMID- 2212274 TI - Cognitive functioning in young "social drinkers": is there impairment to detect? AB - Literature on the cognitive effects of nonexcessive alcohol use suggests that relatively high-quantity-per-occasion use may be related to subsequent decreases in sober-state abstracting skills in adults, but provides no clear prediction for youth. The need to identify persistent alcohol-intake effects on cognition is particularly acute for the period of adolescence and young adulthood because even slight damage may impair developmentally significant skills. We examine the relation between multiple measures of neuropsychological status and both continuous and categorical measures of alcohol-use patterns in an age- and sex stratified sample of 1,308 18-, 21-, and 24-year-olds. The results of correlational and hierarchial regression analyses suggest that cognitive performance bears little direct relation to drinking behaviors in young nonclinical males and females. Although the data provide no strong support for the hypothesis of a causal relationship between alcohol use and cognitive functioning, there is a slight suggestion that frequent high-quantity consumption may become a salient parameter of use as subjects age. Prospective longitudinal data are needed to explore the directional causality of effects. PMID- 2212276 TI - Are people changed by the experience of having an episode of depression? A further test of the scar hypothesis. AB - The purpose of this study was to identify characteristics of individuals before and after their first depressive episode. Subjects were 49 older persons assessed before and after their first depressive episode on depression-related psychosocial variables. The control group consisted of 351 never-depressed individuals. Consistent with previous findings, patients were more likely to be younger, female, and mildly depressed both before and after the episode. In addition, they were more likely to be employed. Following an episode of depression, the recovered patients described their social skills and health as poorer and their interpersonal dependency as greater than the controls. However, on an experiment-wise basis, the number of significant differences were no greater than expected by chance. The stress activation model was examined but did not appreciably enhance the results. Results suggest that most of the psychosocial variables associated with depression are state dependent. PMID- 2212277 TI - Reduced lateralization in verbal dichotic listening in adolescent psychopaths. AB - One possible explanation for previous findings of abnormal linguistic processing in psychopaths is that they are less lateralized for verbal processes. This study tests the hypothesis that adolescent psychopaths show evidence of reduced lateralization on a verbal dichotic listening task. Four self-report and behavioral measures of psychopathy were used to define psychopathy using cluster analytic techniques in 40 juvenile offenders aged 13 to 18 years. Psychopaths were found to have reduced ear asymmetries relative to nonpsychopaths, a result indicating reduced lateralization for verbal material. The effect does not appear to be mediated by group differences in age, ethnic background, IQ, overall performance, left-handedness, selective attention to one ear, or interhemispheric transfer deficits. This result suggests that the previous finding by Hare and McPherson is robust, provides some preliminary validity for the assessment of psychopathy before age 18, and indicates initial support for the utility of cluster analytic techniques in the assessment of psychopathy. PMID- 2212278 TI - Role of maternal functioning and parenting skills in adolescent functioning following parental divorce. AB - While divorce has been associated with impaired child functioning, the mechanisms within the divorce process leading to such an outcome have rarely been examined. The following hypothesis was examined: Divorce is associated with poor parental adjustment or disrupts parenting behavior, or both, which leads to poor adolescent functioning. Subjects were 121 and 93 young adolescents from intact and recently divorced families, respectively, and their mothers and teachers. Mothers completed measures assessing parental conflict and depression, observers coded parenting skills during a mother-adolescent interaction, and teachers completed measures assessing adolescent functioning. Although the magnitude of differences was not large, analyses of variance indicated that the divorced sample was functioning poorer than the married sample on all measures except interparental conflict. Path analysis suggested that parental functioning and parenting skills play a role in adolescent functioning following divorce. PMID- 2212279 TI - Chronic stress and depressive disorders in older adults. AB - Current and lifetime rates of Diagnostic and Statistical Manual (rev. 3rd ed.) disorders were compared in 86 older adults caring for a spouse with a progressive dementia and 86 sociodemographically matched control subjects. Dementia caregivers were significantly more dysphoric than non-care givers. The frequencies of depressive disorders did not differ between groups in the years before care giving, and there were no group differences in first-degree relatives' incidence of psychiatric disorder. During the years they had been providing care, 30% of care givers experienced a depressive disorder (major depression, dysthymia, or depression not otherwise specified) versus 1% of their matched controls in the same time period. Only two care givers who met criteria during care giving had met criteria for a depressive disorder before care giving, and family history was not even weakly related to the identification of at-risk care givers. In contrast to these group differences in depressive disorders, there were no significant differences in other Axis I disorders either before or during care giving. Thus, the chronic strains of care giving appear to be linked to the onset of depressive disorders in older adults with no prior evidence of vulnerability. PMID- 2212280 TI - Inherited predisposition to alcoholism: characteristics of sons of male alcoholics. AB - Sons of male alcoholics (SOMAs) are at markedly heightened genetic risk for the development of alcohol abuse. Study of SOMAs could therefore conceivably increase the efficiency of research aimed at uncovering those heritable factors that predispose to alcoholism. SOMAs manifest observable behavioral, cognitive, and psychophysiological abnormalities while sober and react idiosyncratically to alcohol intoxication. They are most commonly described as conduct disordered and hyperactive, appear heir to a variety of deficits in verbal and abstract cognition, and perform more poorly in the academic environment. SOMAs are characterized by abnormal patterns of cued psychophysiological response, and appear more sensitive to the putatively reinforcing aspects of alcohol intoxication. Various methodological weaknesses permeate the relevant literature. Some straightforward improvements are suggested. PMID- 2212281 TI - Syndrome comorbidity in patients diagnosed with a DSM-III-R anxiety disorder. AB - One hundred thirty patients presenting at an anxiety disorders research clinic were administered a structured interview (i.e., Anxiety Disorders Interview Schedule-Revised). Diagnoses were made in accordance with Diagnostic and Statistical Manual (rev. 3rd ed.) criteria. Seventy percent of patients received at least one additional but secondary Axis I diagnosis. The most common additional diagnoses were simple and social phobia, which were assigned to nearly one third of all patients. In addition, 33% of anxiety disorder patients received an additional diagnosis of a depressive mood disorder (i.e., dysthymia or major depression). The distribution of specific additional diagnoses are presented for each principal anxiety disorder category. The scientific and clinical implications of comorbidity are discussed while considering the relatively high patterns of syndrome comorbidity found in the present study, which is consistent with several earlier studies. PMID- 2212283 TI - Film-induced negative affect triggers overeating in restrained eaters. AB - We tested the effects of film-induced negative affect (i.e., exposure to a frightening film) in 60 women classified as either restrained or unrestrained eaters on the basis of their responses to the Revised Restraint Scale (Herman & Polivy, 1980). Exposure to the frightening film, in contrast to a neutral film, was associated with increases in anxiety, sadness, and anger. High restraint subjects exposed to the frightening film ate more than did equally restrained subjects exposed to a neutral film or low restraint subjects exposed to either film. Thus, negative affect triggered overeating among restrained eaters. Although unrestrained eaters exposed to the frightening film ate less than those who viewed the neutral film, this difference was not statistically significant. These results suggest that negative affect may prompt overeating in persons who attempt to restrict their caloric intake. PMID- 2212282 TI - Schizophrenic deficit in span of apprehension. AB - We investigated two hypotheses about the span of apprehension task in schizophrenia: (a) schizophrenics show performance deficit on the forced-choice (FC) version but not on the full-report (FR) version, and (b) schizophrenic impairment on the FC version is greater when the display subtends a wide visual angle than when it subtends a narrow one. Schizophrenic (n = 21) and normal (n = 22) groups were tested on 3 versions of the task. A narrow-angle FC version was matched psychometrically with a wide-angle one by use of a greater number of noise letters in the narrow version. Schizophrenics reported fewer correct letters than normals on the FR version but did not differ on either the wide or the narrow FC versions. The results imply that schizophrenic deficit is not specific to the FC version and that on the FC version, visual angle is not more important than number of noise letters for demonstrating schizophrenic deficit. PMID- 2212284 TI - Collapse and rebound of a gas-filled spherical bubble immersed in a diagnostic ultrasonic field. AB - This work is concerned with the influence of the finite-amplitude distortion of a driving diagnostic ultrasonic field on the collapse and rebound of a gas-filled spherical microbubble, present in the exposed compressible liquid. Such an analysis is especially important since one of the mechanisms for cavitation damage comes from the very large gas pressures generated at bubble collapse and in the subsequent pressure wave formed by bubble rebound. Gilmore's model [F.R. Gilmore, "The growth or collapse of a spherical bubble in a viscous compressible liquid," Hydrodynamics Lab. Rep. No. 26-4, California Institute of Technology, Pasadena, CA (1952)] for bubble dynamics is used to obtain the motion of the bubble interface when subjected to a pulsed diagnostic ultrasonic field of large amplitude. Knowledge of the bubble motion allows one to derive the pressure distribution around the bubble. Numerical results over a range of initial bubble sizes, acoustic pressures, and frequencies relevant to medical use show that the strength of the pressure spikes radiated by the rebounding bubble depends upon (i) the acoustic frequency (f), (ii) the initial bubble size (R0), and (iii) the magnitude of the pressure amplitude of the fundamental (PF) in a Fourier series description of the distorted pulse. As the pressure spikes propagate outward from the bubble wall, their strength is attenuated as the reciprocal of the distance from the center of collapse. PMID- 2212285 TI - Auditory duration discrimination in the European starling (Sturnus vulgaris). AB - Auditory duration discrimination was studied in the European starling (Sturnus vulgaris, n = 3) using a GO/NOGO-procedure. Acoustic signals were presented by the method of constant stimuli. Duration discrimination limens (DDLs) were determined using signal detection theory (threshold criterion d' = 1.8). Weber fractions delta T/T = 0.23 for reference durations of between 800 and 100 ms, respectively. The DDLs for reference durations of 400 and 200 ms did not differ from those of 800 ms. There was no effect of tone frequency. Weber fractions delta T/T for a decrease in duration were independent of the reference durations and the frequencies tested (average delta T/T = 0.19). Duration discrimination is discussed with respect to data from other animals, and to hypotheses on the perception of signal duration. PMID- 2212286 TI - Patterns of expressive timing in performances of a Beethoven minuet by nineteen famous pianists. AB - The timing patterns of 19 complete performances of the third movement of Beethoven's Piano Sonata op. 31, No. 3, were measured from oscillograms and analyzed statistically. One purpose of the study was to search for a timing pattern resembling the "Beethoven pulse" [Clynes, in Studies of Music Performance (Royal Academy of Music, Stockholm, 1983), pp. 76-181]. No constant pulse was found at the surface in any of the performances. Local patterns could be interpreted as evidence for an "underlying" pulse of the kind described by Clynes, but they could also derive from structural musical factors. On the whole, the artists' timing patterns served to underline the structure of the piece; lengthening at phrase boundaries and at moments of melodic/harmonic tension were the most salient features. A principal components analysis suggested that these timing variations in the Minuet could be described in terms of two orthogonal factors, one capturing mainly phrase-final lengthening, and the other reflecting phrase-internal variation as well as tempo changes. A group of musically experienced listeners evaluated the performances on a number of rating scales. Their judgments showed some significant relations to the measured timing patterns. Principal components analysis of the rating scales yielded four dimensions interpreted as force, individuality, depth, and speed. These preliminary results are encouraging for the development of more precise methods of music performance evaluation. PMID- 2212287 TI - The role of perceived speaker identity in F0 normalization of vowels. AB - In the experiments reported here, perceived speaker identity was controlled by manipulating the fundamental frequency (F0) range of carrier phrases in which speech tokens were embedded. In the first experiment, words from two "hood"-"hud" continua were synthesized with different F0. The words were then embedded in synthetic carrier phrases with intonation contours which reduced perceived speaker identity differences for test items with different F0. The results indicated that when perceived speaker identity differences were reduced, the effect of F0 on vowel identification was also reduced. Experiment 2 indicated that when items presented in carrier phrases are matched for speaker identity and F0 with items in isolation, there is no effect for presentation in a carrier phrase. Experiment 3 involved the presentation of vowels from the "hood"-"hud" continuum in two different intonational contexts which were judged to have been produced by different speakers, even though the F0 of the test word was identical in the two contexts. There was a shift in identification as a result of the intonational context which was interpreted as evidence for the role of perceived identity in vowel normalization. Overall, the experiments suggest that perceived speaker identity is a better predictor of vowel normalization effects than is intrinsic F0. This indicates that the role of F0 in vowel normalization is mediated through perceived speaker identity. PMID- 2212288 TI - Perception of intraphonemic differences by phoneticians, musicians, and inexperienced listeners. AB - Several studies have shown that extensive training with synthetic speech sounds can result in substantial improvements in listeners' perception of intraphonemic differences. The purpose of the present study was to investigate the effects of listening experience on the perception of intraphonemic differences in the absence of specific training with the synthetic speech sounds being tested. Phonetically trained listeners, musicians, and untrained listeners were tested on a two-choice identification task, a three-choice identification task, and an ABX discrimination task using a synthetic [bi]-[phi] continuum and a synthetic [wei] [rei] continuum. The three-choice identification task included the identification of stimuli with an "indefinite" or "ambiguous" quality in addition to clear instances of the opposing phonetic categories. Results included: (1) All three subject groups showed some ability to identify ambiguous stimuli; (2) phonetically trained listeners were better at identifying ambiguous stimuli than musicians and untrained listeners; (3) phonetically trained listeners performed better on the discrimination task than musicians and untrained listeners; (4) musicians and untrained listeners did not differ on any of the listening tasks; and (5) participation by the inexperienced listeners in a 10-week introductory phonetics course did not result in improvements in either the three-choice identification task or the discrimination task. PMID- 2212289 TI - English consonant recognition in noise and in reverberation by Japanese and American listeners. AB - English consonant recognition in undegraded and degraded listening conditions was compared for listeners whose primary language was either Japanese or American English. There were ten subjects in each of the two groups, termed the non-native (Japanese) and the native (American) subjects, respectively. The Modified Rhyme Test was degraded either by a babble of voices (S/N = -3 dB) or by a room reverberation (reverberation time, T = 1.2 s). The Japanese subjects performed at a lower level than the American subjects in both noise and reverberation, although the performance difference in the undegraded, quiet condition was relatively small. There was no difference between the scores obtained in noise and in reverberation for either group. A limited-error analysis revealed some differences in type of errors for the groups of listeners. Implications of the results are discussed in terms of the effects of degraded listening conditions on non-native listeners' speech perception. PMID- 2212290 TI - Place coding of vowel formants for cochlear implant patients. AB - Four multiple-channel cochlear implant patients were tested with synthesized versions of the words "hid, head, had, hud, hod, hood" containing 1, 2, or 3 formants, and with a natural 2-formant version of the same words. The formant frequencies were encoded in terms of the positions of electrical stimulation in the cochlea. Loudness, duration, and fundamental frequency were kept fixed within the synthetic stimulus sets. The average recognition scores were 47%, 61%, 62%, and 79% for the synthesized 1-, 2-, and 3-format vowels and the natural vowels, respectively. These scores showed that the place coding of the first and second formant frequencies accounted for a large part of the vowel recognition of cochlear implant patients using these coding schemes. The recognition of the natural stimuli was significantly higher than recognition of the synthetic stimuli, indicating that extra cues such as loudness, duration, and fundamental frequency contributed to recognition of the spoken words. PMID- 2212292 TI - Modeling the perception of concurrent vowels: vowels with different fundamental frequencies. AB - If two vowels with different fundamental frequencies (fo's) are presented simultaneously and monaurally, listeners often hear two talkers producing different vowels on different pitches. This paper describes the evaluation of four computational models of the auditory and perceptual processes which may underlie this ability. Each model involves four stages: (i) frequency analysis using an "auditory" filter bank, (ii) determination of the pitches present in the stimulus, (iii) segregation of the competing speech sources by grouping energy associated with each pitch to create two derived spectral patterns, and (iv) classification of the derived spectral patterns to predict the probabilities of listeners' vowel-identification responses. The "place" models carry out the operations of pitch determination and spectral segregation by analyzing the distribution of rms levels across the channels of the filter bank. The "place time" models carry out these operations by analyzing the periodicities in the waveforms in each channel. In their "linear" versions, the place and place-time models operate directly on the waveforms emerging from the filters. In their "nonlinear" versions, analogous operations are applied to the output of an additional stage which applied a compressive nonlinearity to the filtered waveforms. Compared to the other three models, the nonlinear place-time model provides the most accurate estimates of the fo's of paris of concurrent synthetic vowels and comes closest to predicting the identification responses of listeners to such stimuli. Although the model has several limitations, the results are compatible with the idea that a place-time analysis is used to segregate competing sound sources. PMID- 2212291 TI - An evaluation of an alternating magnetic field device for monitoring tongue movements. AB - Alternating magnetic field devices hold much promise for tracking movements of multiple articulators, including the tongue, in the midsagittal plane. Here, the accuracy, repeatability, and linearity of one such device, the Articulograph AG 100 (Carstens Medizinelektronik GmbH, Gottingen, West Germany), are evaluated. The results indicate that with proper precautions in transducer calibration and placement, the Articulograph can be a useful tool in speech production research. PMID- 2212294 TI - The effect of modulation coherence on signal threshold in frequency-modulated noise bands. AB - A series of four experiments was undertaken to ascertain whether signal threshold in frequency-modulated noise bands is dependent upon the coherence of modulation. The specific goal was to determine whether a masking release could be obtained with frequency modulation (FM), analogous to the comodulation masking release (CMR) phenomenon observed with amplitude modulation (AM). It was hypothesized that an across-frequency grouping process might give rise to such an effect. In experiments 1-3, maskers were composed of three noise bands centered on 1600, 2000, and 2400 Hz; these were either comodulated or noncomodulated with respect to both FM and AM. In experiment 1, the modulation was sinusoidal, and the signal was a 2000-Hz pure tone; in experiment 2, the modulation was random, and the signal was an FM noise band centered on 2000 Hz. The results obtained showed that, given sufficient width of modulation, thresholds were lower in a coherent FM masker than in an incoherent FM masker, regardless of the pattern of AM or signal type. However, thresholds in multiband maskers were usually elevated relative to that in a single-band masker centered on the signal. Experiment 3 demonstrated that coherent FM could be discriminated from incoherent FM. Experiment 4 gave similar patterns of results to the respective conditions of experiments 2 and 3, but for an inharmonic masker with bands centered on 1580, 2000, and 2532 Hz. While within-channel processes could not be entirely excluded from contributing to the present results, the experimental conditions were designed to be minimally conducive to such processes. PMID- 2212293 TI - Effect of masker level on overshoot. AB - Overshoot refers to the phenomenon where signal detectability improves for a short-duration signal as the onset of that signal is delayed relative to the onset of a longer duration masker. A popular explanation for overshoot is that it reflects short-term adaptation in auditory-nerve fibers. In this study, overshoot was measured for a 10-ms, 4-kHz signal masked by a broadband noise. In the first experiment, masker duration was 400 ms and signal onset delay was 1 or 195 ms; masker spectrum level ranged from - 10-50 dB SPL. Overshoot was negligible at the lowest masker levels, grew to about 10-15 dB at the moderate masker levels, but declined and approached 0 dB at the highest masker levels. In the second experiment, the masker duration was reduced to 100 ms, and the signal was presented with a delay of 1 or 70 ms; masker spectrum level was 10, 30, or 50 dB SPL. Overshoot was about 10 dB for the two lower masker levels, but about 0 dB at the highest masker level. The results from the second experiment suggest that the decline in overshoot at high masker levels is probably not due to auditory fatigue. It is suggested, instead, that the decline may be attributable to the neural response at high levels being dominated by those auditory-nerve fibers that do not exhibit short-term adaptation (i.e., those with low spontaneous rates and high thresholds). PMID- 2212295 TI - Temporal decline of masking and comodulation detection differences. AB - Comodulation detection differences (CDDs) were studied using flanking bands that were either gated simultaneously with the signal band (burst) or gated at varying times prior to signal onset (fringed). Used for these experiments were a signal band centered at 1250 Hz and four flanking bands centered at 450, 850, 1650, and 2050 Hz; all bands were 100 Hz wide. In different conditions, the temporal envelope of the signal band was either the same as (correlated), or different from (uncorrelated), the common envelope of the four flanking bands, or the temporal envelopes of all of the bands were different (all-uncorrelated). For 8 of the 13 listeners, signal detectability improved by as much as 25 dB as the temporal fringe of the flanking bands was increased from 5 to about 700 ms. This temporal decline of masking was similar, but not identical, for the correlated, uncorrelated, and all-uncorrelated conditions. Results of this sort are reminiscent of several related findings that have been attributed to auditory adaptation or enhancement, or to a temporally developing critical-band filter. The other 5 of the 13 listeners were generally more sensitive than the majority, and they showed little or no improvement in detectability as fringe duration was varied. Large individual differences of this sort are not uncommon in the adaptation and comodulation literatures. As signal duration was changed from 50 to 240 ms, temporal integration was less in the correlated condition than in the uncorrelated condition, thereby producing a larger CDD with the longer signal. When the fringe followed the observation interval instead of preceding it, the results were equivocal because detectability improved for the majority of subjects and worsened for the minority. In follow-up experiments, different subsets of these four flanking bands were used. When temporal gaps of varying duration were inserted into the flanking band(s) immediately prior to the observation intervals, it was found that a temporal gap as long as 355 ms was not sufficient to reset the mechanisms underlying the temporal decline of masking. PMID- 2212296 TI - Comodulation masking release as a function of bandwidth and time delay between on frequency and flanking-band maskers. AB - The threshold for a signal masked by a narrow band of noise centered at the signal frequency (the on-frequency band) may be reduced by adding to the masker a second band of noise (the flanking band) whose envelope is correlated with that of the first band, an effect called comodulation masking release (CMR). This paper examines CMR as a function of masker bandwidth and time delay between the envelopes of the on-frequency and flanking bands. The 1.0-kHz sinusoidal signal had a duration of 400 ms. The on-frequency band was presented alone (reference condition) or with the flanking band. The flanking-band envelope was either correlated or uncorrelated with that of the on-frequency band. Flanking-band center frequencies ranged from 0.25-2.0 kHz. The flanking band was presented either in the same ear as the on-frequency band (monaural condition) or in the opposite ear (dichotic condition). The noise bands had bandwidths of 6.25, 25, or 100 Hz. In the correlated conditions, the flanking-band envelope was delayed with respect to that of the on-frequency band by 0, 5, 10, or 20 ms. For the 100-Hz bandwidth, CMRs were small (typically less than 1 dB) in both monaural and dichotic conditions at all delay times. For the 25-Hz bandwidth, CMRs were about 3.5 dB for the 0-ms delay, and decreased to about 1.5 dB for the 20-ms delay. For the 6.25-Hz bandwidth, CMRs averaged about 5 dB and were almost independent of delay time. The results suggest that the absolute delay time is not the critical variable determining CMR. The magnitude of CMR appears to depend on the correlation between the envelopes of the on-frequency and flanking bands. However, the results do not support a model of CMR that assumes that signal threshold corresponds to a constant change in across-band envelope correlation when the correlation is transformed to Fisher's z. PMID- 2212297 TI - Two-, three-, and four-interval forced-choice staircase procedures: estimator bias and efficiency. AB - Threshold estimates for multiple-interval forced-choice staircase procedures were studied using computer simulations. A sigmoidal psychometric function shape governed the hypothetical subject's responses in the simulations. Parameters varied included the number of trials, the step size for stimulus level change, and decision rules that targeted 70.7% and 79.4% correct performance. Each threshold estimate was calculated by averaging the stimulus levels at which a reversal a stimulus level direction occurred. The results of the simulations suggest that, as the number of alternatives is increased from 2 to 4, the variability of repeated threshold estimates decreases or remains constant, and the accuracy of the estimator, in most cases, improves. A subset of the simulations was compared with data obtained in a detection-in-noise task. The behavioral data were consistent with the simulation results. Two major conclusions were reached. First, 3- and 4-interval forced-choice (IFC) procedures are more efficient than a 2IFC procedure with a decision rule that targets 70.7% correct performance even when the additional time required to complete 3- and 4IFC trials is considered. Second, the accuracy of 2IFC procedures can be improved by fitting the trial history of a staircase run using probit analysis. PMID- 2212298 TI - Forward masking in patients with cochlear implants. AB - Forward masking was measured in 12 patients with cochlear implants. The amount of masking (in microamps) decreased linearly as a function of the logarithm of the signal delay from masker offset. Normalized forward-masking recovery functions for cochlear implants were similar to normalized functions of normal-hearing listeners, indicating that the mechanism of psychophysical forward masking is retrocochlear. These results indicate that the logarithm of acoustic amplitude should be mapped to microamps to produce normal forward masking in implanted patients. Despite the fact that the forward-masking recovery functions were similar across all patients, their performance with their speech processor varied widely. PMID- 2212299 TI - Loudness growth in 1/2-octave bands (LGOB)--a procedure for the assessment of loudness. AB - In this paper, a method that has been developed for the assessment and quantification of loudness perception in normal-hearing and hearing-impaired persons is described. The method has been named LGOB, which stands for loudness growth in 1/2-octave bands. The method uses 1/2-octave bands of noise, centered at 0.25, 0.5, 1.0, 2.0, and 4.0 kHz, with subjective levels between a subject's threshold of hearing and the "too loud" level. The noise bands are presented to the subject, randomized over frequency and level, and the subject is asked to respond with a loudness rating (one of: VERY SOFT, SOFT, OK, LOUD, VERY LOUD, TOO LOUD). Subject responses (normal and hearing-impaired) are then compared to the average responses of a group of normal-hearing subjects. This procedure allows one to estimate the subject's loudness growth relative to normals, as a function of frequency and level. The results may be displayed either as isoloudness contours or as recruitment curves. In its present form, the measurements take less than 30 min. The signal presentation and analysis is done using a PC and a PC plug-in board having a digital to analog converter. PMID- 2212300 TI - Range resolution and the possible use of spectral information in the echolocating bat, Eptesicus fuscus. AB - Individuals of the echolocating bat Eptesicus fuscus were trained to discriminate simulated two-wave-front targets with internal time delays of 0 to 100 microns between the wave fronts from a one-wave-front target. The ability of bats to discriminate between such targets can be referred to as range resolution. In Eptesicus fuscus, this ability is limited to distinct internal time delays (12, 32-40, and 52-100 microns) between the two wave fronts of a double-wave-front target. Analysis of the simulated two-wave-front echoes reveals periodic frequency minima in the spectrum. Position and separation of these spectral minima depend on the time delay between the two wave fronts. The occurrence of spectral minima within the frequency range of the first harmonic in the echo of the bats' echolocation call correlates to the bats' ability to discriminate a one wave-front echo from two-wave-front echoes, suggesting that Eptesicus fuscus uses spectral differences within the first harmonic in echoes for range resolution. PMID- 2212301 TI - Spectral weights in profile listening. AB - The COSS analysis suggested by Berg [B. G. Berg, J. Acoust. Soc. Am. 86, 1743 1746 (1989)] is applied to a profile listening task. The listener's task is to detect an increment in the level of the middle component of an n-component spectrum. The overall level of the components is randomly selected from a 20-dB range on each presentation; thus the detection task is essentially one of detecting a change in spectral shape. To implement the COSS analysis, a small perturbation in level is added to each component of the complex. COSS functions are generated from these perturbations, and the spectral weight that the listener assigns to each component is estimated. Data are reported for n = 3, 5, and 11 components and for perturbations with standard deviations of 0.5, 1, and 2 dB. The estimated weights are similar to those derived for an optimum detector; namely, the level at the signal component is compared with the average level of the nonsignal components. This result supports the view that profile analysis involves an across-channel comparison process. The pattern of weights also provides insight into differences among listeners. In a separate experiment, the spectral weights of a very poor profile listener are estimated, and the pattern of the weights suggests reasons for the inferior detection performance. PMID- 2212302 TI - Auditory temporal integration and the power function model. AB - The auditory temporal integration function was studied with the objective of improving both its quantitative description and the specification of its principle independent variable, stimulus duration. In Sec. I, temporal integration data from 20 studies were subjected to uniform analyses using standardized definitions of duration and two models of temporal integration. Analyses revealed that these data were best described by a power function model used in conjunction with a definition of duration, termed assigned duration, that de-emphasized the rise/fall portions of the stimuli. There was a strong effect of stimulus frequency and, in general, the slope of the temporal integration function was less than 10 dB per decade of duration; i.e., a power function exponent less than 1.0. In Sec. II, an experimental study was performed to further evaluate the models and definitions. Detection thresholds were measured in 11 normal-hearing human subjects using a total of 24 single-burst and multiple burst acoustic stimuli of 3.125 kHz. The issues addressed are: the quantitative description of the temporal integration function; the definition of stimulus duration; the similarity of the integration processes for single-burst and multiple-burst stimuli; and the contribution of rise/fall time to the integration process. A power function in conjunction with the assigned duration definition was again most effective in describing the data. Single- and multiple-burst stimuli both seemed to be integrated by the same central mechanism, with data for each type of stimulus being described by a power function exponent of approximately 0.6 at 3.125 kHz. It was concluded that the contribution of the rise/fall portions of the stimuli can be factored out from the rest of the temporal integration process. In Sec. III, the conclusions that emerged from the review of published work and the present experimental work suggested that auditory temporal integration is best described by a power function in conjunction with the assigned duration definition. The exponent for the power function is typically less than 1.0, and varies with frequency and hearing level. Second, a means of empirically assaying the contribution of the rise-fall portions of the stimuli is presented and evaluated. Finally, properties of a central auditory integrator are hypothesized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212303 TI - Auditory temporal integration in the normal-hearing and hearing-impaired cat. AB - Temporal integration functions obtained from human subjects with sensorineural hearing loss have shallower slopes than the functions obtained from normal hearing subjects. The present investigation was designed to explore this relation in animals in order to compare normal-hearing cats and humans. Auditory temporal integration functions were measured for five cats before and after they were exposed to a 2-kHz tone at 110 dB SPL for 48 h. To measure the temporal integration functions, ten stimuli were used that had overall durations from 8.32 to 275 ms and that were configured either as single or multiple tone bursts of 6.25 kHz. Twelve thresholds for each stimulus were obtained from each animal before and after the sound exposure. Pre- and postexposure audiograms were also obtained and the mean permanent threshold shift at 6.25 kHz was 32.5 dB. Exponential and power function models were used to describe the data. The exponential model (with grand-mean data) yielded a pre-exposure time constant (tau) of 188 ms [mean absolute residual (MAR) of 1.5 dB] and a postexposure tau of 21 ms (MAR of 1.4 dB). For the power function model with grand-mean data, the pre-exposure slope was 6.6 dB per decade of duration (MAR of 1.4 dB) and a postexposure slope of 3.8 dB per decade of duration (MAR of 0.7 dB). The results indicated that the slope of the temporal integration function was less steep after sensorineural hearing loss of cochlear origin, and that the power function model was more effective in describing temporal integration data for the range of stimulus durations employed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212304 TI - The role of single-channel cues in synchrony perception: the summed waveform. AB - Human observers are able to discriminate between simultaneously presented bands of noise having envelopes that are identical (synchronous) rather than statistically independent (asynchronous). The possibility that the detection of envelope synchrony is based on cues available in a single critical band, rather than on a simultaneous comparison of envelopes extracted via independent critical bands, is examined. Two potential single-channel cues were examined, both relying on the assumption that information present in the envelope of the summed bands is available to the listener. One such single-channel cue is the rms of the envelope of the summed waveform; the envelope is more deeply modulated for the summed synchronous bands than for the summed asynchronous bands. The second cue examined was envelope regularity; the envelope of the summed synchronous bands has periodic envelope minima, while the summed asynchronous bands exhibit aperiodic envelope minima. Psychophysical results suggest that such within-channel cues may be both available to, and utilized by, the listener when the component bands are separated by less than one-third of an octave. PMID- 2212305 TI - Temporal integration in amplitude modulation detection. AB - Thresholds for detecting sinusoidal amplitude modulation (AM) of a wideband noise carrier were measured as a function of the duration of the modulating signal. The carrier was either; (a) gated with a duration that exceeded the duration of modulation by the combined stimulus rise and fall times; (b) presented with a fixed duration that included a 500-ms carrier fringe preceding the onset of modulation; or (c) on continuously. In condition (a), the gated-carrier temporal modulation transfer functions (TMTFs) exhibited a bandpass characteristic. For AM frequencies above the individual subject's TMTF high-pass segment, the mean slope of the integration functions was - 7.46 dB per log unit duration. For the fringe and continuous-carrier conditions [(b) and (c)], the mean slopes of the integration functions were, respectively, - 9.30 and - 9.36 dB per log unit duration. Simulations based on integration of the output of an envelope detector approximate the results from the gated-carrier conditions. The more rapid rates of integration obtained in the fringe and continuous-carrier conditions may be due to "overintegration" where, at brief modulation durations, portions of the unmodulated carrier envelope are included in the integration of modulating signal energy. PMID- 2212306 TI - Restarting the adapted binaural system. AB - Previous experiments using trains of high-frequency filtered clicks have shown that for lateralization based on interaural difference of time or level, there is a decline in the usefulness of interaural information after the signal's onset when the clicks are presented at a high rate. This process has been referred to as "binaural adaptation." Of interest here are the conditions that produce a recovery from adaptation and allow for a resampling of the interaural information. A train of clicks with short interclick intervals is used to produce adaptation. Then, during its course, a treatment such as the insertion of a temporal gap or the addition of another "triggering" sound is tested for its ability to restart the binaural process. All of the brief triggers tested are shown to be capable of promoting recovery from adaptation. This suggests that, while the binaural system deals with the demands of high-frequency stimulation with rapid adaptation, it quickly cancels the adaptation in response to stimulus change. PMID- 2212307 TI - Age changes in pure-tone hearing thresholds in a longitudinal study of normal human aging. AB - Hearing thresholds were obtained on 813 adult males (20-95 years) measured at 11 frequencies ranging from 0.125-8 kHz from pure-tone audiograms collected over a 20-year period from 1968 to 1987. Audiograms taken at two to six different ages spanning a maximum observation period of 15 years were obtained for each male belonging to one of seven different age groups (20,30,...,80 years) based on the age of initial observation. The males were participants in the Baltimore Longitudinal study of Aging (BLSA), a multidisciplinary community-based study of normal human aging. Changes in hearing thresholds occurred in all age groups during the 15-year follow-up period. For example, at 0.5 and 8 kHz for combined left and right ears there was an average longitudinal loss of 5.7-7.6 and 5.1 21.1 dB, respectively, for 20-year-olds, 10.0-12.7 and 35.2-53.0 dB for 50-year olds, and 22.9-48.5 and 69.0-84.5 dB for 80-year-olds. As in results from previous cross-sectional studies, hearing loss in the males 70 years and older is greatest at the highest frequencies. The rate of change for these older males is faster in the speech-range frequencies 0.5-2 kHz than in the higher frequencies, since their hearing has already diminished at the high frequencies. PMID- 2212308 TI - The behavior of the acoustic distortion product, 2f1-f2, from the human ear and its relation to auditory sensitivity. AB - The acoustic intermodulation distortion product 2f1-f2 (ADP) was measured in human subjects to investigate (1) the dependence of ADP level on stimulus parameters and (2) the relationship between ADP level and auditory sensitivity. The frequency ratio (f2/f1), at which ADP level is maximal, varies only slightly across frequency and subjects. The average optimal ratio is 1.225. Beyond the maximum, the ADP level declines with increasing f2/f1 ratio, at rates of up to 250 dB/oct. As the level of one stimulus is increased relative to the other, the ADP grows, saturates, and in most cases shows a bendover. Maximum distortion is generated when L 1 exceeds L 2. Growth rate and saturation point are dependent on which stimulus is incremented and on the level of the stationary stimulus. With optimal stimulus parameters (levels below 60 dB SPL; L 1 greater than L 2 by 15 dB; f2/f1 = 1.225), ADP levels are commonly 30 dB below L 2. Patterns of ADP level across frequency vary between subjects, but are repeatable within each subject. As the frequency of one or both of the stimuli is varied, changes in ADP level exhibit a broadly featured pattern with a fine structure superimposed upon it. This fine structure was compared with the features in the stimulus frequency emission spectrum in one subject. With appropriate stimulus parameters, half of our subjects show a statistically significant correlation across frequency, between ADP level and auditory sensitivity at the corresponding f1 frequency. Our results suggest that, with low levels of stimulation, ADP measurements could form the basis of an objective measure of cochlear function in human subjects. PMID- 2212310 TI - Synchronization of spontaneous otoacoustic emissions to a 2f1-f2 distortion product. AB - Synchronization of spontaneous otoacoustic emissions to a cubic distortion frequency fs = 2f1-f2 has been studied. Stimulus, consisting of two primary tones at frequency f1 and f2, could easily be filtered out of the microphone signal. This enabled us to monitor emission phase with respect to synchronization frequency fs, by recording zero-crossing moments of the microphone signal. When primaries were sufficiently loud (typically 30 dB SPL), phase fluctuated around a constant value: The emission was constantly synchronized to fs. Lowering primary levels (to typically 20 dB SPL) resulted in 2 pi-phase jumps at random moments: The emission occasionally slipped out of synchronization, trying to maintain its own natural frequency f0. This behavior can be described as synchronization of an oscillator (frequency f0) to a sinusoidal force (frequency fs) in the presence of noise. PMID- 2212309 TI - Measurement of acoustic distortion reveals underlying similarities between human and rodent mechanical responses. AB - The level of 2f1-f2 acoustic distortion product (ADP) measured in the meatus during two-tone stimulation was compared with N 1 thresholds measured at the round window for the guinea pig. A significant inverse relation was found between distortion level and N 1 threshold. A similar relationship has also been reported for ADP level and subjective thresholds in half the human ears measured [S.A. Gaskill and A.M. Brown, J. Acoust. Soc. Am. 88, 821-839 (1990)]. Guinea pig and human ADP levels behave similarly in response to varying stimulus parameters. The ADP levels grow to a maximum and decline with increasing stimulus separation. The decline is steeper in the human ear. In both species, ADP growth as a function of stimulus level is approximately 1 with covaried stimuli; more gradual with the level of f2 (L 2) alone increasing and steeper when the level of f1 (L 1) alone is increased. The latter slopes are strongly influenced by the level of the stationary L 2 and are less steep in the human ear. A link has been proposed between differences in ADP behavior and differences in auditory filter bandwidth in the two species. Guinea pigs show little intersubject variability in ADP level. They do not show the fine structure in distortion level across frequency or the variation in growth rate seen in human responses. Differences in organ of Corti fine structure may underly these differences. PMID- 2212312 TI - On the accuracy of models for predicting sound propagation in fitted rooms. AB - The objective of this article is to make a contribution to the evaluation of the accuracy and applicability of models for predicting the sound propagation in fitted rooms such as factories, classrooms, and offices. The models studied are 1:50 scale models; the method-of-image models of Jovicic, Lindqvist, Hodgson, Kurze, and of Lemire and Nicolas; the emprical formula of Friberg; and Ondet and Barbry's ray-tracing model. Sound propagation predictions by the analytic models are compared with the results of sound propagation measurements in a 1:50 scale model and in a warehouse, both containing various densities of approximately isotropically distributed, rectangular-parallelepipedic fittings. The results indicate that the models of Friberg and of Lemire and Nicolas are fundamentally incorrect. While more generally applicable versions exist, the versions of the models of Jovicic and Kurze studied here are found to be of limited applicability since they ignore vertical-wall reflections. The Hodgson and Lindqvist models appear to be accurate in certain limited cases. This preliminary study found the ray-tracing model of Ondet and Barbry to be the most accurate of all the cases studied. Furthermore, it has the necessary flexibility with respect to room geometry, surface-absorption distribution, and fitting distribution. It appears to be the model with the greatest applicability to fitted-room sound propagation prediction. PMID- 2212311 TI - Time course of adaptation and recovery from adaptation in the cat auditory-nerve neurophonic. AB - The auditory-nerve neurophonic (ANN) reflects the ensemble response of phase locked firing in single auditory-nerve fibers to sustained signals. Consequently, neural response properties such as adaptation and recovery from adaptation can be observed. In this study, ANN responses to 800-Hz, 100-ms tones presented at 10-30 dB SL were recorded using bipolar platinum-iridium electrodes placed on the auditory nerve of the cat. The cat ANN adaptation properties were determined and fit to the equation: A(tp) = Yre(-tp/tau Ar) + Yse(-tp/tau As) + Ass. The rapid time constant of adaptation (tau Ar) was invariant across stimulus level, with a mean value of 4.8 (+/- 2.1) ms. The short-term time constant (tau As) decreased approximately 21 ms for each 10-dB increase in probe amplitude. The mean tau As was 116 ms at 10 dB SL, 83.2 ms at 20 dB SL, and 73.5 ms at 30 dB SL. The ANN recovery from adaptation data was analyzed and fit to the equation: A(delta t) = Amax - Yre(-delta t/tau Rr) - Yse(-delta t/tau Rs). Here, tau Rr, the rapid time constant of recovery, and tau Rs, the short-term time constant, were independent of masker intensity in the studied range, with values of 16.2(+/- 9.8) and 125(+/ 50.1) ms, respectively. The results of this study indicate that ANN time constants are comparable to those measured for single units and that the adaptation behavior of phase-locked and nonphase-locked activity appears to be similar. PMID- 2212314 TI - Program of the 120th meeting of the Acoustical Society of America. San Diego, California, 26-30 November 1990. Abstracts. PMID- 2212313 TI - On the level-dependent penalty for impulse sound. AB - At relatively low A-weighted equivalent levels (Leq), road-traffic sounds are rated to be less annoying than impulse sounds. The differences, however, decrease with increasing Leq of the sounds, which indicates that the penalty for impulse sound seems to be level dependent. It was questioned whether the decrease of the penalty with increasing Leq might, at least partly, have been a consequence of the use of the ten-point rating scale. In experiments 1 and 2, the relevance of the level-dependent correction was therefore studied further by using the method of adjustment. The mean results again showed that, at least for gunfire sounds (small arms), the penalty is level dependent. The drawing of firm conclusions, however, was hampered by a relatively large bias in the adjustments. In addition, the overall size of the penalty was lower than obtained in previous rating experiments. The question about the relevance of the level-dependent penalty was reopened in experiment 3 by applying the method of paired comparison. The results confirm the previous findings obtained with the rating experiments: For gunfire sounds at relatively low indoor Leq values, a penalty of about 10 dB is required, and a penalty lower than 5 dB can be applied only in conditions with rather high sound exposure. The results further showed that especially at indoor Leq values higher than about 45 to 50 dB(A), application of a negative penalty may become relevant for specific sounds such as those produced by the 0.50-in. machine gun. Consequently, acoustic measures from which to predict the value of the penalty are highly needed. PMID- 2212316 TI - Implantology. Does it merit specialty status? PMID- 2212315 TI - Hepatitis developments. PMID- 2212317 TI - Update on implants--techniques, technology explored. PMID- 2212318 TI - Education in implant dentistry. AB - Currently, relatively few dentists are qualified to practice implant dentistry; the demand for dental implants may soon exceed the profession's capacity to deliver this type of treatment. Accordingly, there is a salient need for national standards of education in the field. Implant education varies widely for practicing dentists, postdoctoral students, and predoctoral students. Although many schools are starting to teach implant dentistry in their predoctoral curricula, clinical and laboratory experience is limited. There are not enough trained professors, funding for new departments is limited, and change is often met with resistance. It is anticipated that within the decade, schools will establish departments, divisions, or sections dedicated to education in implant dentistry, despite these obstacles. PMID- 2212319 TI - Dental education--meeting the demands of implant dentistry. AB - Implant education is undergoing a transition from short, often superficial, continuing education to extended, hands-on experiences, based on clinical case studies. Dental schools previously ignored the need for in-depth implant education. Policy decisions related to future education are being considered in most dental undergraduate and postgraduate curricula. A broad-based implant education concept is proposed to meet the demands of a rapidly developing discipline. PMID- 2212321 TI - Goals and limitations of implant prosthodontics. AB - Goal-driven treatment plans promote an accurate differential diagnosis resulting in appropriate implant prosthodontic treatment. The identification, understanding, and acceptance of the limitations of therapy assist both the doctor and the patient in achieving their objectives and minimizing disappointments. The implementation of such a regimen helps to achieve a successful result. PMID- 2212320 TI - Implant prosthodontics contribute to restorative dentistry. AB - This paper is directed toward dental practitioners who accomplish the prosthodontic procedures for dental implants. It includes a discussion of most of the major steps in current implant dentistry. Several implant systems are compared with a look at the future of implant prosthodontics. PMID- 2212322 TI - Problem solving in implant dentistry. AB - Dental implants have become an accepted form of dental care, with reported functional 5-year success rates of 90% and higher. These impressive statistics include, but do not identify, the problems that may have been created by clinical ineptitude. Diagnostic acumen and preventive measures at each stage of the implant treatment can avoid many problems. Also, appropriate measures of timely recognition, rescue, and repair can often restore ailing implants and their prosthetic appliances to full function. PMID- 2212323 TI - An overview of implant hardware. AB - This paper overviews dental implants emphasizing design concepts, material composition, and prosthetic abutments. Within the space limitations, all systems can not be shown in total and we do not infer superiority or inferiority with the inclusion or exclusion of any design, concept, or abutment. PMID- 2212324 TI - The fixed mandibular implant: its use in reconstructive prosthetics. AB - The main advantages of the FMI are immediate denture placement and function, the versatility for denture construction, and the absolutely parallel abutments that make prosthetic adaptation easy. During the submental approach, the oral and maxillofacial surgeon can perform cosmetic surgery of the submental fat pad and chin. There is usually less pain and swelling as compared with the intraoral dental procedure for placing four or five implants. The FMI is an excellent option for the anterior edentulous mandible or deformed mandible when fixed or fixed removable dentures or overdenture is needed. The team approach allows the surgeon and prosthetic dentist to combine their skills in the management of edentulous patients. PMID- 2212325 TI - Technique for screw-type implants. PMID- 2212326 TI - Implant systems incorporating the hollow-basket concept. AB - The hollow-basket design provides precise fit and stability after insertion, minimal bone destruction, and maximal bone-to-implant contact. Both systems, with careful attention to surgical protocol, will achieve osseointegration. PMID- 2212327 TI - The blade implant. PMID- 2212328 TI - The restorative and surgical technique for the full maxillary subperiosteal implant. AB - The edentulous atrophic maxilla represents one of the most challenging implant restorative opportunities. When prescribed within the appropriate diagnostic range and performed by a highly skilled and experienced practitioner, the full maxillary subperiosteal implant is a predictable solution for the patient with an edentulous atrophic maxilla. PMID- 2212329 TI - Technique for placement of root form implants of the finned or serrated type. PMID- 2212330 TI - Ramus frame implant technique. PMID- 2212331 TI - A new technique for the subperiosteal implant. PMID- 2212332 TI - Facial emphysema after dental treatment. PMID- 2212333 TI - The debate continues ... PMID- 2212334 TI - The advent of surgical periodontal treatment. PMID- 2212336 TI - Only diamonds are forever. PMID- 2212335 TI - Punch biopsy. PMID- 2212337 TI - Diagnosing periodontal diseases. AB - At present, the diagnosis of periodontal disease requires a clinical evaluation of the patient including visual findings, the use of the periodontal probe, and radiographs. No test is available to evaluate disease activity. In specific cases, adjunctive procedures may also be useful. The identification of pathogenic microorganisms may aid in evaluating the periodontal status of special patients. However, these are not required for an adequate diagnosis of the common adult form of chronic periodontitis. PMID- 2212338 TI - Reviewing nonsurgical periodontal therapy. AB - Selection of the appropriate case and clinical competency in treatment modalities results in success in nonsurgical periodontal therapy. The patient with early periodontitis with significant local factors in the form of professionally accessible plaque and calculus is the most receptive to nonsurgical periodontal treatment. The clinician must make decisions centering around the important question, "Can the patient, or moreover, can the therapist delivering the debridement, gain access to the microbial subgingival plaque on a frequent basis below the host defense threshold of the respective patient?" If the answer is "yes," nonsurgical periodontal therapy will be rewarding. If the answer is "no," other modalities such as periodontal surgery must be instituted. PMID- 2212339 TI - Lengthening clinical crowns. AB - Finding a solution to the short clinical crown is based on an appreciation of the biological width of attachment plus the dimensional requirements of sound restorative procedures. The collective talents of restorative dentist, orthodontist, and periodontist often are needed to cope with the problem. PMID- 2212340 TI - Surgical pocket reduction. AB - It is not possible within the scope of this paper to describe in any detail each of the aforementioned procedures. These can be found in the various textbooks and journals on clinical periodontology. Instead, the objectives of treatment, the spectrum of techniques available, and the rationale for their use have been described. Periodontal surgery should be performed only under certain conditions: the patient must be physically and mentally competent to undergo any type of surgery, and should understand and agree to the procedure and to postoperative management. Finally, periodontal surgery should only be considered when nonsurgical therapy will not accomplish the desired result. When periodontal surgery for pocket elimination is performed for selected defects that have been properly evaluated after a debridement and healing period, and is executed with technical competence and proper postoperative care, it can preserve the dentition affected by periodontal disease. PMID- 2212341 TI - Using periodontal plastic surgery techniques. AB - In the 1980s, mucogingival surgery evolved into periodontal plastic surgery with various techniques designed to produce root coverage in areas of marginal tissue recession, to augment deficient ridges, and to lengthen crowns in cases of excessive gingival display. Periodontal plastic surgery not only enables the dentist to reconstruct but also to regenerate lost tissues. PMID- 2212343 TI - Premolarization of a fractured maxillary first molar: a multidisciplinary treatment. AB - The diagnosis and treatment of a fractured maxillary first molar are described in this case report of a 28-year-old male. Successful treatment of the retained palatal root of the fractured molar, referred to as premolarization, ensued from integration of endodontic, orthodontic, periodontic, and fixed prosthodontic care. PMID- 2212342 TI - Dental implants used for periodontal patients. AB - For those performing implant treatment, continued research and reports of long term successful results are essential to evaluating the validity of implants, especially when variables such as design and surface treatment are introduced. The dental profession has enthusiastically embraced the clinical results of implant treatment and its benefits to the patient. However, just as patients who undergo periodontal and restorative treatment must continue a regular long-term routine of maintenance therapy to ensure their dental health, so must those patients who receive dental implants. Both the periodontist who places the implants and the dentist who fabricates the prosthetic replacement must work cooperatively to deliver a healthy restoration that will function for many years. PMID- 2212344 TI - An esthetic approach to vertical root extrusion in a patient with an anterior open bite: report of case. AB - A previous attempt to locate the root canal system in the maxillary left central incisor with a bur created a perforating root defect at the level of the alveolar crest. The patient received root canal therapy. Next, vertical root extrusion was chosen to expose sound tooth structure apical to the defect so that a crown could be constructed. With an anterior open bite, the natural crown was left intact and it was possible to position the anchor bar in an incisal and lingual position, maintaining esthetics for the patient during both the extrusive and stabilization phases of treatment. PMID- 2212345 TI - Incidence of lingual nerve trauma and postinjection complications in conventional mandibular block anesthesia. AB - Trauma to the lingual nerve is potential risk factor for patients receiving mandibular block anesthesia. This paper describes the results of a patient survey of 9,587 conventional mandibular blocks received by 2,289 adults. The incidence of lingual nerve trauma and postinjection complications is reported along with an associated analysis of the duration of complications, procedures at the time of incident, the side of occurrence (right or left), and gender ratios. In addition, recommendations for patient evaluation, treatment, and follow-up care are discussed. PMID- 2212346 TI - Type 2 diabetes mellitus and periodontal disease. AB - The relationship between type 2 diabetes mellitus and periodontal disease was evaluated in 2,878 Pima Indians of the southwestern United States. Two independent measures of periodontal disease, probing attachment loss and radiographic bone loss, were used to compare prevalence and severity of periodontal disease in diabetic and nondiabetic subjects. In all age groups studied, subjects with diabetes had a higher prevalence of periodontal disease, indicating that diabetes may be a risk factor for periodontal disease. PMID- 2212347 TI - Periodontal therapy: reviewing subgingival irrigations and future considerations. PMID- 2212348 TI - Proliferative mass found in the gingiva. AB - The clinical course of peripheral ossifying fibroma is slow and the growth of most lesions is limited in size, usually up to 1.5 cm. Complaints are rare unless the surface becomes ulcerated, or the lesion compromises oral function or esthetic appearance. Treatment is surgical excision with close postoperative follow-up. Tooth extraction is seldom necessary. Proper surgical intervention, which includes excision of reactive tissue down to periosteum, affords a low recurrence rate of 14% to 16%. PMID- 2212349 TI - Improved morphologic characterization of atrial septal aneurysm by transesophageal echocardiography: relation to cerebrovascular events. AB - Transthoracic and transesophageal echocardiography was performed in 23 consecutive adult patients with an atrial septal aneurysm. In three patients with a cerebrovascular event the diagnosis was established by the transesophageal approach only. Interatrial shunting on transthoracic imaging with use of echocardiographic contrast imaging or Doppler color mapping, or both, was detected in 7 (41%) of 17 patients. On performing contrast imaging in combination with color flow mapping during transesophageal echocardiography, positive shunting was demonstrated in 15 (83%) of 18 patients. Echocardiographic identification of multiple fenestrations (n = 4) and thrombus within the aneurysm (n = 2) could be achieved for the first time by transesophageal ultrasound application. Cerebrovascular events occurred in 12 (52%) of 23 patients and were regarded as being definitely thromboembolic in 10 (43%); 8 (67%) of the 12 patients had repeated cerebral events. Except for mitral valve prolapse in one patient, no other potential cardiac source of embolism could be identified despite the use of transesophageal echocardiography. A thickening of the aneurysmal membrane greater than or equal to 5 mm was found in 9 (75%) of 12 patients with versus 3 (27%) of 11 patients without a cerebrovascular event (p less than 0.05); this proved to be the only significant difference between the two patient groups. The mechanism of embolization may be both primary thrombus formation within the aneurysm and paradoxic embolization through an interatrial communication as demonstrated by the findings in two patients. It is concluded that atrial septal aneurysm is a cardiac abnormality with thromboembolic potential. In patients with this lesion and a history of an embolic event, long term anticoagulant therapy is indicated. PMID- 2212350 TI - Transesophageal Doppler color flow mapping assessment of atrial septal defect. AB - Transesophageal Doppler color flow imaging was performed in 19 adult patients (mean age 35 years) with an atrial septal defect demonstrated by cardiac catheterization or at surgery, or both. The transesophageal study correctly identified and classified 19 of 19 shunts in contrast to 16 of 18 shunts identified by the transthoracic approach. The area of the atrial septal defect was calculated by assuming it to be circular and taking the maximal Doppler color flow jet width at the defect site as its diameter. The pulsed Doppler sample volume was placed parallel to the shunt flow direction at the defect site to obtain the mean velocity and flow duration. From these values, the shunt volume was calculated as a product of the defect area, mean velocity, flow duration and heart rate. The calculated shunt flow volume obtained by transesophageal study showed a good correlation with shunt flow volume (r = 0.91, p less than 0.001) and pulmonary to systemic blood flow ratio (r = 0.84, p less than 0.001) obtained at cardiac catheterization. The size of the defect by transesophageal Doppler color flow mapping correlated fairly well with the size estimated at surgery (r = 0.73, p = 0.004). It is concluded that transesophageal Doppler color flow imaging is useful in the detection and classification of atrial septal defects and in the assessment of shunt volumes. PMID- 2212351 TI - How accurate is SPECT thallium scintigraphy? PMID- 2212352 TI - Agreement on the accuracy of thallium stress testing. PMID- 2212355 TI - Training programs in the United States in adult cardiology, pediatric cardiology and cardiothoracic surgery. PMID- 2212356 TI - ACC testimony on the increased demand for cardiovascular services. PMID- 2212353 TI - SPECT thallium imaging in the diagnosis of myocardial ischemia. PMID- 2212354 TI - The electrocardiogram in the acute coronary syndromes. PMID- 2212357 TI - Cognition in the era of technology: "seeing the shades of gray". PMID- 2212359 TI - The elderly, the very elderly and traditional practice patterns. PMID- 2212358 TI - Outlook after acute myocardial infarction in the very elderly compared with that in patients aged 65 to 75 years. AB - Little is known concerning late outcome and prognostic factors after acute myocardial infarction in the very elderly (greater than 75 years of age). Accordingly, this study compared the clinical course and mortality rate for up to 1 year in a large multicenter data base that included 702 patients greater than 75 years of age (mean +/- SD 81 +/- 4 years), with a less elderly subset of 1,321 patients between 65 and 75 years of age (mean 70 +/- 3 years). The postdischarge 1 year cardiac mortality rate was 17.6% for those greater than 75 years of age compared with 12.0% for patients between 65 and 75 years of age (p less than 0.01). There were differences in the prevalence of several factors, including female gender, history of angina pectoris, history of congestive heart failure, smoking habits and incidence of congestive heart failure during hospitalization. Multivariate analyses of predictors of cardiac death in hospital survivors selected different factors as important in the two age subgroups; age was selected in the 65 to 75 year age group but was not an independent predictor in the very elderly. The survival curves beginning at day 10 for patients 65 to 75 and in those greater than 75 years old were similar for up to 90 days but diverged later. In the very elderly, 63% of late cardiac deaths were sudden or due to new myocardial infarction, similar to the causes of 67% of deaths in the younger age group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212361 TI - Percutaneous aortic balloon valvuloplasty: relief of obstruction to outflow or inflow? PMID- 2212360 TI - Changes in left ventricular diastolic performance after aortic balloon valvuloplasty: acute and late effects. AB - To evaluate acute and follow-up changes in left ventricular diastolic performance, simultaneous digital left ventriculography and micromanometry were performed in 49 patients undergoing aortic balloon valvuloplasty. All patients improved symptomatically after valvuloplasty, and 26 returned 6.3 +/- 1.5 months later for follow-up catheterization. Immediately after valvuloplasty, aortic valve area increased (before 0.5 +/- 0.2 versus after 0.8 +/- 0.2 cm2, p less than 0.01), cardiac output (before 4.3 +/- 1.2 versus after 4.4 +/- 1.3 liters/min) and ejection fraction (before 51 +/- 18% versus after 52 +/- 17%) did not change and diastolic indexes worsened, signified by a decrease in peak filling rate (before 247 +/- 80 versus after 226 +/- 78 ml/s, p less than 0.01) and increase in the time constant of isovolumetric relaxation (tau) (before 78 +/ 29 versus after 96 +/- 40 ms, p less than 0.01) and the modulus of chamber stiffness (before 0.107 +/- 0.071 versus after 0.141 +/- 0.083, p less than 0.01). At follow-up catheterization, 16 patients continued to have symptomatic improvement (group 1) and 10 had recurrence of symptoms (group 2). Aortic valve area, cardiac output and ejection fraction at follow-up catheterization in both groups were similar and unchanged from values before valvuloplasty.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212362 TI - Coronary angioplasty in patients with severe left ventricular dysfunction. AB - The applications for coronary angioplasty have greatly expanded and the procedure is now increasingly used in complex and potentially high risk conditions. This report describes the short- and long-term effects of coronary angioplasty in 61 patients with severely depressed left ventricular function (ejection fraction less than or equal to 35%) with unstable or refractory anginal symptoms, or both, in whom revascularization was necessary despite increased risk. In a retrospective analysis of 1,260 patients undergoing angioplasty between January 1985 through December 1987, 61 had an ejection fraction less than or equal to 35%. The common clinical presentation was unstable angina (70%) with or without recent myocardial infarction. Mean left ventricular ejection fraction was 27 +/- 6%. Forty-five patients (74%) had multivessel disease. Clinical success after angioplasty was achieved in 55 patients (90%). Major complications (death, infarction and emergency bypass surgery) occurred in five patients (8.2%), with death in two (3.2%). During long-term (mean 21 +/- 11 months) follow-up study of the 55 patients with successful angioplasty, 13 (23%) died, including 3 of noncardiac causes, and 11 (20%) had clinically symptomatic recurrence. Continued clinical success was present in 39 patients (71%), of whom 28 (51%) were event free patients and 11 (20%) had clinical recurrence; a successful second angioplasty procedure was performed in 9 because of restenosis. Thus, in patients with depressed left ventricular function, coronary angioplasty can be performed with a short-term success rate comparable to that of routine angioplasty or surgical procedures. However, acute complications are more frequent and the late mortality rate is higher than in patients with less depressed function. PMID- 2212363 TI - Coronary angioplasty after coronary bypass surgery: initial results and late outcome in 422 patients. AB - From 1978 to 1988, coronary angioplasty was performed in 422 patients with prior coronary artery bypass surgery (264 patients with native coronary artery angioplasty and 158 patients with graft angioplasty). Angioplasty was successful in 84%, unsuccessful but uncomplicated in 11% and complicated by one or more major cardiac events in 5% (myocardial infarction 5%, emergency bypass surgery 2% and death 0.2%). Follow-up data were obtained in 99% of 356 patients with successful angioplasty. At a mean of 33 +/- 26 months, 92% were alive, 73% had improvement in angina and 61% were free of angina. One or more of the following late events occurred in 67 patients (19%): myocardial infarction (6%), elective reoperation (13%) and cardiac death (6%). Repeat angioplasty was performed in 27%, with a success rate of 89% and no deaths. Initial success rates were equal in native vessel versus graft angioplasty, but late outcome was less favorable with the latter because of a higher rate of infarction (11% versus 4%, p less than 0.05) and need for reoperation (19% versus 10%, p less than 0.05). The initial success rate was higher in vein grafts less than 1 year old compared with grafts 1 to 4 years or greater than 4 years after operation (92% versus 85% versus 83%, respectively) and adverse late events were less frequent after angioplasty in recent vein grafts (less than 1 year 13%, 1 to 4 years 35%, greater than 4 years 29%; less than 1 versus greater than 1 year, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212364 TI - Natural history of hypertrophic cardiomyopathy in the elderly. AB - The prognosis of patients diagnosed as having hypertrophic cardiomyopathy at advanced age has not been well defined. This study details follow-up information obtained for 95 patients initially diagnosed as having hypertrophic cardiomyopathy at age greater than or equal to 65 years. Seventy-five percent of patients were symptomatic, as defined by the presence of chest pain, dyspnea or syncope, and the mean ventricular septal thickness was 20 mm. The median duration of follow-up study was 4.2 years. The survival rate at 1 and 5 years was 95% and 76%, respectively, which was not significantly different from that an age- and gender-matched control group. Of patients presenting with New York Heart Association functional class I or II dyspnea, only 18% progressed to class III or IV during the follow-up period. However, patients presenting with class III dyspnea had a 1 year mortality rate of 36%, significantly higher than that of control subjects (p less than 0.003). Of the echocardiographic variables, indexed left atrial size was most strongly associated with reduced survival (p less than 0.008). These results suggest that the prognosis of elderly patients with hypertrophic cardiomyopathy is generally favorable. Certain clinical and echocardiographic variables appear to be of use in identifying patients with a less favorable prognosis. PMID- 2212365 TI - Prognostic importance of the serum magnesium concentration in patients with congestive heart failure. AB - Magnesium abnormalities are common in patients with congestive heart failure but the clinical and prognostic significance of an abnormal serum magnesium concentration in this disorder has not been investigated. Therefore, the relation between serum magnesium concentration and the clinical characteristics and long term outcome of 199 patients with chronic heart failure was evaluated. The serum magnesium concentration was less than 1.6 mEq/liter in 38 patients (19%), within the normal range in 134 patients (67%) and greater than 2.1 mEq/liter in 27 patients (14%). Patients with hypomagnesemia had more frequent ventricular premature complexes and episodes of ventricular tachycardia than did patients with a normal serum magnesium concentration (p less than 0.05). Even though the two groups were similar with respect to severity of heart failure and neurohormonal variables, patients with a low serum magnesium concentration had a significantly worse prognosis during long-term follow-up (45% versus 71% 1 year survival, p less than 0.05). Patients with hypermagnesemia had more severe symptoms, greater neurohormonal activation and worse renal function than did patients with a normal serum magnesium concentration but tended to have fewer ventricular arrhythmias. Hypermagnesemic patients had a worse prognosis than did those with a normal magnesium concentration (37% versus 71% 1 year survival, p less than 0.05). In conclusion, the measurement of serum magnesium concentration provides important clinical and prognostic information in patients with chronic heart failure. PMID- 2212366 TI - Cardiac rhythm disturbances early after orthotopic heart transplantation: prevalence and clinical importance of the observed abnormalities. AB - To precisely define the incidence, type and consequences of cardiac arrhythmias early after heart transplantation, 25 cardiac transplant recipients were monitored continuously for 728 days from the day of surgery to discharge or death. A subset of 15 patients had sinus node function studies with overdrive suppression performed weekly at the time of endomyocardial biopsy. Results revealed sinus bradycardia in 10 patients (40%) and junctional bradycardia in 6 (24%). Supraventricular tachycardia in the form of atrial tachycardia, atrial fibrillation and atrial flutter occurred in 11 patients (44%). Ventricular tachycardia occurred in 15 patients (60%) and was nonsustained in all. Cardiac pacing for 1,403 h was used in nine patients with a pulse rate less than 50 beats/min; seven recovered and permanent pacing was instituted in two. In the subgroup that had sinus node function studies, seven patients were identified with clinical bradyarrhythmia; each had abnormal sinus node recovery time (greater than 1,400 ms) and abnormal corrected sinus node recovery time (greater than 525 ms) in at least one study. These seven patients also had a significantly prolonged ischemic time (236 +/- 26 versus 159 +/- 68 min, p less than 0.01). In conclusion, cardiac arrhythmias, particularly ventricular tachycardia and bradyarrhythmia, occur more commonly early after orthotopic heart transplantation than has previously been reported. Sinus node dysfunction due to prolonged organ ischemic time, antiarrhythmic drug use or surgical trauma, alone or in combination, may contribute to these arrhythmias. PMID- 2212367 TI - Comparison of physiologic ejection fraction responses to activities of daily living: implications for clinical testing. AB - The recent development of the VEST, an ambulatory radionuclide detector, to measure left ventricular ejection fraction may enhance the detection of ischemia during daily activities in patients with coronary artery disease. The normal range and determinants of ejection fraction responses to stimuli other than physical exercise, however, are not adequately characterized. Therefore, ejection fraction responses to various activities were measured in 18 normal subjects utilizing the VEST. Uniform increases (greater than 5%) in ejection fraction were seen during physical exercise, uniform decreases were seen during cold pressor testing and modest changes (including decreases greater than 5%) were seen in ejection fraction during mental stress, micturition and hyperventilation. Different forms of stress produced significantly different changes in ejection fraction, even when values were controlled for changes in heart rate. Ventricular loading conditions in the form of enhanced blood pressure responses during mental stress may have contributed to the relatively smaller changes in ejection fraction compared with those during exercise. Subjects demonstrating a decrease in ejection fraction during mental stress did not differ from other subjects in hemodynamic reactivity during mental testing but did have evidence of increased parasympathetic tone during cold pressor and bicycle exercise testing. The results reveal that normal ejection fraction response differs among varying physiologic stimuli. These changes are in part related to changes in heart rate and blood pressure; however, other factors, such as neurohumoral regulation, may also play a role. These findings indicate that the patient's activity and the setting in which it occurs must be considered when interpreting ambulatory ejection fraction responses. PMID- 2212368 TI - A new single catheter technique for simultaneous measurement of action potential duration and refractory period in vivo. AB - In vivo correlations of action potential duration measured by a monophasic action potential catheter and effective refractory period measured by a separate pacing catheter have been poor, probably because of the known variability of both action potential duration and effective refractory period between different ventricular sites. In this study, a new quadripolar contact electrode catheter designed for simultaneous pacing and monophasic action potential recording at closely adjacent sites (2 mm separation between recording electrodes and pacing electrodes) was tested in five closed chest dogs and four patients. Dog studies: Pacing thresholds were extremely low, ranging from 0.02 to 0.25 mA (mean +/- SD 0.099 +/ 0.051, n = 36) and were stable over time (less than 20% increase during 1 h of continuous pacing). Because of the close proximity of pacing and recording electrodes, the pacing artifact nearly coincided with the monophasic action potential upstroke. Because of the low pacing threshold, however, pacing artifacts were small (33 +/- 17% of the monophasic action potential amplitude at twice diastolic threshold strength) and did not affect the duration or configuration of the simultaneously recorded monophasic action potential. The short stimulus response time and the undisturbed monophasic action potential signal fidelity during pacing allowed precise simultaneous measurements of action potential duration and effective refractory period at the same endocardial site.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212369 TI - An effective and adaptable transvenous defibrillation system using the coronary sinus in humans. AB - With use of a coronary sinus catheter electrode, a right ventricular catheter electrode and a chest wall patch electrode system, defibrillation threshold voltage, current and energy were measured with four distinct transvenous defibrillation techniques delivered in random sequence in each of 12 survivors of cardiac arrest immediately before implantation of a standard epicardial patch defibrillation system. The four transvenous defibrillation techniques were 1) single pathway monophasic pulsing, 2) single pathway biphasic pulsing, 3) dual pathway sequential pulsing, and 4) dual pathway simultaneous pulsing. A transvenous defibrillation method was considered to be potentially useful only if the defibrillation threshold was less than or equal to 500 V (less than or equal to 15 J delivered energy). The 500 V value would allow a 2:1 defibrillation safety margin for a device with a maximal output of 30 J. No single transvenous pulsing technique was uniformly superior in efficacy. However, by choosing the best pulsing technique for each patient, it was possible to obtain an average defibrillation threshold of 410 +/- 135 V leading edge voltage, 7.2 +/- 2.5 A leading edge current and 11.3 +/- 7.4 J delivered energy for the group of 12 patients. With the ability to vary defibrillation technique, transvenous antiarrhythmic device implantation would have been possible in 10 (83%) of the 12 patients at or below a 15 J defibrillation threshold cutoff point. In contrast, if only one transvenous defibrillation method had been used, as few as 5 and at most 8 of the 12 patients would have been candidates for a transvenous defibrillation system given a 15 J defibrillation threshold cutoff point for insertion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212370 TI - The automatic implantable cardioverter-defibrillator in young patients. AB - An international survey identified 40 patients less than 20 years old who underwent surgical implantation of an automatic implantable cardioverter defibrillator (AICD). There was a history of aborted sudden cardiac death or sustained ventricular tachycardia in 92.5% of these patients. Twenty-two patients (55%) had structural heart disease; dilated and hypertrophic cardiomyopathy were the most common diagnoses. Eighteen patients (45%) had primary electrical abnormalities including seven with the congenital long QT syndrome. There were no perioperative deaths associated with device implantation. Concomitant drug therapy was administered to 75% of the patients. Defibrillator discharge occurred in 70% of the patients, with 17 patients (42.5%) receiving at least one appropriate shock. There were two sudden and two nonsudden deaths at 28.2 months' median follow-up. Sudden death-free survival rates by life table analysis at 12 and 33 months were 0.94 and 0.88, respectively. Total survival rates at 12 and 33 months were 0.94 and 0.82, respectively. The AICD represents an effective treatment approach for young patients with life-threatening ventricular tachyarrhythmias. PMID- 2212371 TI - Accuracy of prospective two-dimensional/Doppler echocardiography in the assessment of reparative surgery. AB - Between January 1987 and January 1989, all 129 patients (aged 11 days to 25 years, median 39 months) undergoing both an echocardiographic examination and cardiac catheterization after reparative surgery were prospectively included in a study to assess the accuracy of combined two-dimensional and Doppler color flow imaging. The patient diagnoses were transposition of the great arteries (n = 20), tetralogy of Fallot (n = 38), coarctation of the aorta (n = 24), complete atrioventricular (AV) canal (n = 15), atrial septal defect (n = 8), ventricular septal defects (n = 3), pulmonary stenosis (n = 4), aortic stenosis (n = 8) and subaortic stenosis (n = 9). In arterial tract stenosis, there was high correlation between Doppler estimates and catheterization-derived measurements of residual right ventricular outflow tract obstruction in patients after the arterial switch operation for transposition of the great arteries (r = 0.95) as well as in patients after corrective repair of tetralogy of Fallot (r = 0.84). In semilunar/AV valve regurgitation, graded as none, mild, moderate or severe, echocardiographic estimates correlated exactly with angiographic grading in 84% and differed by one angiographic grade in the other 16%. In residual left to right shunting, no hemodynamically significant shunt was missed by echocardiography. For residual shunts at the ventricular level (n = 32), addition of Doppler color flow imaging improved the sensitivity (from 63% to 94%) and the negative predictive value (from 88% to 98%). In elevated right ventricular pressure, Doppler-derived right ventricular-right atrial pressure estimates in 24 patients correlated well with catheterization measurements (r = 0.93). Combined two-dimensional and Doppler color flow echocardiography was highly accurate in the prospective evaluation of these four types of postoperative residual. PMID- 2212373 TI - Intraoperative echocardiography for congenital heart disease. PMID- 2212372 TI - Comparative roles of intraoperative epicardial and early postoperative transthoracic echocardiography in the assessment of surgical repair of congenital heart defects. AB - In 94 consecutive patients undergoing surgical repair of congenital heart defects the results of intraoperative (after cardiopulmonary bypass) epicardial two dimensional and Doppler color flow imaging were compared with those of sequential transthoracic echocardiography performed within 24 h of surgery and again before hospital discharge to define the precise role of intraoperative imaging. In 6 of 7 patients with a residual defect requiring immediate surgical revision, intraoperative imaging correctly identified the defect; spectral Doppler imaging underestimated or did not identify a residual outflow tract gradient in 17 patients. Left atrioventricular (AV) valve regurgitation after repair of complete AV septal defect was underestimated in three patients. Although intraoperative documentation of good ventricular function was usually associated with a good outcome, in three patients poor systemic ventricular function after cardiopulmonary bypass was not associated with early mortality. A minor degree of shunting around the patch was a common finding on epicardial and early postoperative imaging and persisted at the time of hospital discharge in 17 of 46 patients who had undergone patch closure of a ventricular septal defect as part of the surgical procedure. Additional trabecular septal defects were missed on color flow imaging after cardiopulmonary bypass in three patients, one of whom required subsequent reoperation. Although intraoperative two-dimensional and color flow imaging permitted the recognition of the majority of residual defects requiring immediate revision, residual outflow obstruction or AV valve regurgitation was usually underestimated. PMID- 2212374 TI - The daylong pattern of the antianginal effect of long-term three times daily administered isosorbide dinitrate. AB - Three times daily administration of isosorbide dinitrate may avoid much of the tolerance seen with more frequent dosing. To determine the daylong pattern of the antianginal effect of three times daily isosorbide dinitrate, eight men with stable exertional angina and a positive exercise test were studied. The subjects had demonstrated increased exercise duration in response to oral isosorbide dinitrate therapy and absence of complete tolerance to long-term three times daily isosorbide dinitrate. Treadmill exercise to onset of angina was performed over 2 days at 8 AM, 9 AM, 11 AM, 1 PM, 2 PM, 4 PM, 6 PM and 7 PM. On one day each patient received isosorbide dinitrate at 8 AM, 1 PM and 6 PM in a previously titrated dose (mean 27.5 mg), which had been taken three times daily for at least 2 weeks. On the other day at the same hours each patient received double blind a placebo identical in appearance to isosorbide dinitrate. One hour after the 8 AM dose of isosorbide dinitrate, mean systolic blood pressure at rest had fallen by 19 mm Hg and mean exercise time to angina increased by 200 s. However, by 11 AM exercise time had returned to control level. One hour after the 1 PM dose of isosorbide dinitrate, exercise time increased by a mean of 150 s but was again at control level 2 h later.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212375 TI - Myocardial amiodarone and desethylamiodarone concentrations in patients undergoing cardiac transplantation. AB - Myocardial amiodarone and desethylamiodarone concentrations were measured at multiple sites in the explanted heart in four patients who underwent cardiac transplantation. Patients were taking amiodarone, 200 to 400 mg/day (mean 300 +/- 115), for 88 to 428 days (mean 229 +/- 148). The mean cumulative dose was 58 +/- 21.3 g. Plasma amiodarone concentration in three subjects was 204, 312 and 419 ng/ml and desethylamiodarone concentration was 268, 513 and 880 ng/ml, respectively. Significant interindividual variability in myocardial concentrations of amiodarone and desethylamiodarone was observed (p less than 0.05). Mean myocardial amiodarone concentration ranged from 4 +/- 1.0 to 29 +/- 17.2 micrograms/g (p less than 0.05); mean desethylamiodarone concentration ranged from 22 +/- 8.8 to 141 +/- 102.5 micrograms/g (p less than 0.05). At each site, save for fat, myocardial desethylamiodarone concentration was higher than amiodarone concentration. Greater intraindividual variability was observed in myocardial desethylamiodarone compared with amiodarone concentration particularly in septal and scar tissue (p = NS). No significant relation was found between myocardial concentration and duration of treatment. In patients with significant ventricular disease, usefulness of plasma amiodarone and desethylamiodarone concentration to estimate myocardial concentration is limited by intra- and interindividual variability. PMID- 2212376 TI - Effects of benazepril and metoprolol OROS alone and in combination on myocardial ischemia in patients with chronic stable angina. AB - The efficacy of benazepril, metoprolol OROS and their combination was evaluated in 29 patients (42 to 74 years of age) with chronic stable angina and documented coronary artery disease in a placebo-controlled, double-blind, crossover trial using serial quantitated exercise testing and ambulatory electrocardiographic (ECG) monitoring. The mean (+/- SEM) exercise time was 8.5 +/- 0.7 min with placebo, 8.3 +/- 0.6 min (95% confidence interval [CI]-1.06 to 0.54) with benazepril, 9.4 +/- 0.5 min (95% CI -0.32 to 2.14) with metoprolol OROS and 9.6 +/- 0.5 min (95% CI -0.25 to 2.47) with the combination of benazepril and metoprolol OROS. The mean exercise time to the development of 1 mm ST segment depression was prolonged from 6.0 +/- 0.6 min with placebo to 6.3 +/- 0.6 min (95% CI -0.93 to 1.45) with benazepril, 7.9 +/- 0.5 min (95% CI 0.83 to 3.0) with metoprolol OROS and 8.1 +/- 0.6 min (95% CI 0.88 to 3.29) with the combination of benazepril and metoprolol OROS. Benazepril did not alter the rest or maximal heart rate, whereas metoprolol OROS alone and in combination significantly lowered the heart rate at rest and during maximal exercise. Systolic blood pressure at rest was nonsignificantly reduced, whereas diastolic blood pressure was lowered significantly by all treatments in comparison with placebo. At maximal exercise, only metoprolol OROS, whether given alone or in combination with benazepril, was able to blunt significantly systolic blood pressure and rate pressure product.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212377 TI - Is there a role for angiotensin-converting enzyme inhibitors in the treatment of chronic myocardial ischemia? PMID- 2212379 TI - Early and late effects of captopril treatment after large myocardial infarction in rats. AB - The early (after 21 days) and late (after 4 months) effects of continuous treatment with captopril on left ventricular performance, weight and volumes were studied in rats with myocardial infarction. Early effects were examined in rats subjected to coronary ligation and randomized to either immediate treatment with captopril (2 g/liter drinking water) starting 2 h after surgery or no treatment. After 21 days, the treated group showed reductions in mean arterial, left ventricular systolic and left ventricular end-diastolic pressures compared with untreated rats. Right and left ventricular weight and left ventricular volumes were decreased and the ejection fraction index was increased by captopril treatment. To study the late effects of captopril, a second group of rats was randomized to immediate captopril treatment (starting 2 h after surgery), delayed captopril treatment (starting 21 days after surgery) or no treatment. When studied after 4 months of treatment, rats started on captopril treatment 2 h after infarction showed no differences compared with rats started on treatment 21 days after infarction. Treatment with captopril for 4 months produced changes that were similar to those in rats treated for 21 days. Captopril treatment improved hemodynamic function after myocardial infarction in rats examined after either 21 days or 4 months of treatment. The extent of the benefit was similar in the two treatment periods. Initiation of captopril therapy immediately after infarction did not appear to produce a greater effect than treatment started at 21 days after infarction in rats studied after the drug had been administered for 4 months. PMID- 2212378 TI - Does intracoronary infusion of Fluosol-DA 20% prevent left ventricular diastolic dysfunction during coronary balloon angioplasty? AB - Distal intracoronary infusion of the perfluorochemical Fluosol-DA 20% has been shown to prevent systolic dysfunction during coronary artery balloon occlusion in coronary angioplasty. To assess its effect on global diastolic dysfunction, a randomized, single-blind, crossover protocol comparing intracoronary infusion of Fluosol or no infusion (control) was performed during 60 s balloon inflations in 10 patients (mean age 67 years) undergoing coronary angioplasty. Assessment of global systolic and diastolic function was obtained with high fidelity micromanometer measurements of left ventricular pressure. Eighteen pairs of balloon inflations (Fluosol versus control) were analyzed. Patients reported significantly less severe chest pain during inflations accompanied by Fluosol compared with control. However, during coronary balloon occlusion, no significant differences in the changes from baseline values were observed between Fluosol and control with regard to ventricular relaxation, including the time constant of early ventricular relaxation (tau) and maximal rate of fall in left ventricular pressure (maximal negative dP/dt). No differences between Fluosol and control were observed in terms of the increase in end-diastolic pressure or minimal diastolic pressure during balloon inflation. Mean systolic pressure decrease from baseline values was greater during control than during Fluosol inflations (-9.0 +/- 3.3 mm Hg, p = 0.013), but no significant difference was observed in the change in maximal rate of rise in left ventricular pressure (maximal positive dP/dt). These results suggest that Fluosol does not preserve global left ventricular diastolic function during coronary balloon occlusion, possibly because of its limited oxygen delivery capability relative to arterial blood. PMID- 2212380 TI - Heart rate variability before and after myocardial infarction in conscious dogs at high and low risk of sudden death. AB - Heart rate variability has been demonstrated both experimentally and clinically to be of prognostic importance in determining mortality after myocardial infarction. However, no paired studies have been reported to examine heart rate variability before and after myocardial infarction. The hypothesis was tested that low values of heart rate variability provided risk assessment both before and after myocardial infarction with use of an established canine model of sudden cardiac death. Risk for sudden death was assessed 1 month after myocardial infarction by a protocol in which exercise and myocardial ischemia were combined; dogs that developed ventricular fibrillation were classified at high risk for sudden death (susceptible) and the survivors were considered low risk (resistant). In resistant dogs, myocardial infarction did not affect any measure of heart rate variability: 1) mean RR interval, 2) standard deviation of the mean RR interval, and 3) the coefficient of variance (standard deviation/RR interval). By contrast, after myocardial infarction, susceptible dogs showed significant decrease in all measures of heart rate variability. Before myocardial infarction, no differences were seen between susceptible and resistant dogs. However, 30 days after infarction, epidemiologic analysis of the coefficient of variance showed high sensitivity and specificity (88% and 80%, respectively), predicting susceptibility. Therefore, results of analysis of 30 min of beat to beat heart period at rest 30 days after myocardial infarction are highly predictive for increased risk of sudden death. PMID- 2212381 TI - Echocardiographic definition of the left ventricular centroid. I. Analysis of methods for centroid calculation from a single tomogram. AB - Quantitation of myocardial contraction requires a frame of reference. Most investigators have sought a single reference frame per image, centered in some manner with respect to the mass of myocardium. Because there is no anatomic marker for the center of the heart, many different approaches have been pursued to identify a centroid of the left ventricle. The issue of whether the reference should be fixed throughout the cardiac cycle or float from image to image has been addressed in previous studies, but the more fundamental question of how a centroid can best be defined has not been answered. This study examines this basic issue by analysis of variance from observer to observer, cycle to cycle, animal to animal and method to method. Both endocardial and epicardial borders were digitized twice by each of two observers at 1/30 s intervals spanning the cardiac cycle for each of three cardiac cycles in six normal dogs. The left ventricular centroid was calculated by six methods: center of endocardial coordinates, center of epicardial coordinates, center of mid-myocardial (average) coordinates, center of endocardial area, center of epicardial area and center of mid-myocardial (average) area. The path of each centroid was correlated between observers and correlation coefficients were transformed for analysis of variance. This analysis indicates a best approach to centroid definition through distinct minimization of the variance: the best of the six methods proved to be center of endocardial area. PMID- 2212382 TI - Echocardiographic definition of the left ventricular centroid. II. Determination of the optimal centroid during systole in normal and infarcted hearts. AB - Although two-dimensional echocardiography is widely used in both clinical and experimental evaluations of regional cardiac wall motion, there is no established clinical method for quantitative analysis of the wall motion, not even for the normal radial motion observed in short-axis images. Measurement of radial wall motion requires determination of a centroid from which the radii emanate. Depending on its definition, the centroid is variously affected throughout systole by cardiac translation, regional wall motion and any shift of the subject position or transducer. A floating centroid is defined relative to the ventricular walls frame by frame, whereas a fixed centroid never moves with respect to the transducer. Evaluation of the best approach to definition of a centroid was previously presented (part I, this issue). The next question is how to use the centroid. This study examines which of four centroid applications provides the best reference for quantifying regional wall motion during systole. Method 1 is a floating centroid (defined separately for every image frame), method 2 uses the end-diastolic centroid as a fixed reference for all image frames, method 3 uses the end-systolic centroid as a fixed reference and method 4 uses the average as a fixed reference. Wall motion was measured with respect to each of these centroids by determining radial wall motion from end-diastole to end-systole and correlating radial motion throughout the cardiac cycle with that in normal control hearts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212383 TI - Recollections of pioneers in nutrition: fifty years in nutrition. PMID- 2212384 TI - Recollections of pioneers in nutrition: from starvation to cholesterol. PMID- 2212385 TI - Adequacy of a vegetarian diet at old age (Dutch Nutrition Surveillance System). AB - To assess the adequacy of a vegetarian diet at old age, the dietary intake (assessed through dietary history with cross-check) of 44 apparently healthy lacto-(ovo-)vegetarians, aged 65-97 years, was evaluated. Adequacy was assessed by a comparison of nutrient intake with (Dutch) recommendations and by evaluating data on nutritional status. The results were also compared with data of elderly omnivores. In contrast to elderly omnivores, percentages of energy from protein (13%), fat (37%), and carbohydrates (50%) as well as P/S ratio (0.63) were close to or within the range of Dutch guidelines regarding a healthy diet (percentages of energy from protein, fat, and carbohydrates 10-15, 30-35, and 55%, respectively: P/S ratio 0.5-1.0). For most of the micronutrients studied intake was adequate, and nutrient density of the vegetarian diet was higher than of the omnivorous diet. However, the supply of zinc (average daily intake 8.5 and 7.6 mg for men and women, respectively), iron (because of lower bioavailability of nonheme iron), vitamin B12 (women only: intake 2.3 micrograms/day), and water (daily intake less than 1600 ml for 30% of the vegetarians) need special attention, considering the relatively high prevalence of a marginal status of these nutrients. In conclusion, a lacto-(ovo-)vegetarian diet can be adequate at old age, provided that it is carefully planned, especially with respect to the supply of iron, zinc, and vitamin B12. PMID- 2212386 TI - Physical activity and condition, dietary habits, and serum lipids in second-year medical students. AB - Level of physical activity has been found to be an independent risk factor for coronary heart disease. Because lifestyle and dietary habits are frequently established by early adulthood, we examined the physical activity, physical fitness, body composition, plasma lipids, and diets of a group of second-year medical students. Medical students were studied because of the presumption that they were knowledgeable about exercise and appropriate diet and would have future influence on their patients. A questionnaire which assessed physical activity was returned by 69 (89%) of the 80 students. Over 50% reported no hard or very hard physical activity either during the week or on weekends. Three subjects were smokers. Body composition, cardiovascular fitness, and plasma lipids were assessed in 20 subjects selected at random from the 69. Five of the 15 men, but none of the five women, had greater-than-desirable body fat. Cardiovascular fitness was at least average compared to normal values, but three had hypertension at rest and 12 had hypertensive responses to exercise. Seven of the men had LDL cholesterol above 130 mg/dl and three had LDL:HDL ratios greater than 3. There was a positive correlation (r = 0.5, p = 0.02) between hard/very hard activity assessed by questionnaire and VO2max and a negative correlation (r = 0.4, p = 0.05) between VO2max and percent fat. All 20 subjects reported above average to severe amounts of stress. Analysis of a 48-hr diet record of 22 students showed an average consumption of 47% carbohydrates, 17% protein, and 36% fat. The polyunsaturated/saturated ratio was 0.43.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212387 TI - Blood magnesium parameters do not differ with age. AB - The relationship between age and blood magnesium (Mg) parameters has not been defined. Mg measurements in plasma, red blood cells (RBCs), and mononuclear blood cells (MBCs) were made in 104 normal volunteers (43 males and 61 females, ages 11 75 years). MBCs were separated from blood using a discontinuous Ficoll-Hypaque gradient. The mean values (+/- SEM) were as follows: plasma Mg 1.63 +/- 0.01 mEq/L, RBC Mg 4.55 +/- 0.06 mEq/L, MBC Mg content 72.8 +/- 1.0 fg/cell, and MBC Mg concentration 19.6 +/- 0.3 mEq/L. We compared these parameters with age (intervals of 10 years) using analysis of variance (ANOVA) and found no significant differences (p greater than 0.05). Thus, plasma, RBC, and MBC Mg parameters do not vary significantly between the ages of 11 and 75 years. PMID- 2212388 TI - Maternal and fetal plasma vitamin E to total lipid ratio and fetal RBC antioxidant function during gestational development. AB - Placental transfer of vitamin E was investigated from 19 to 35 weeks of gestation by analysis of fetal and maternal blood samples for total tocopherol, total lipids, and fetal red blood cell antioxidant reserves. Fifty-two fetal blood samples were obtained under ultrasonographic guide by percutaneous umbilical blood sampling. Thirteen were from fetuses with gestational age less than or equal to 22 weeks (x serum vitamin E = 0.4 +/- 0.14 mg/dl), 12 were from fetuses at 23-27 weeks gestation (x serum vitamin E = 0.4 +/- 0.21 mg/dl), and 27 were from fetuses with gestational age 28-38 weeks (x serum level = 0.37 +/- 0.18). Total lipid levels ranged from 140 to 216 mg/dl. Maternal plasma vitamin E concentrations correlated significantly with concurrent values in the fetus. There were no significant differences in serum vitamin E levels or vitamin E to total lipid ratio in samples from early, mid, or late gestation in either the mother or fetus. Red blood cell antioxidant reserve on samples from 18 fetuses were grossly abnormal by three different functional assays. On the basis of these data, placental transfer of vitamin E appears to be relatively constant through advancing gestation. Red blood cell antioxidant reserve is uniformly low. PMID- 2212389 TI - Dietary manipulation as a primary treatment strategy for pregnancies complicated by diabetes. AB - The mainstay of management for gestational diabetic women (GDM) has been dietary. If it is inadequate to sustain normoglycemia, insulin therapy must be initiated. We studied whether we could prevent macrosomia by insulin therapy based on four daily self blood glucose levels (SBG). Fifty GDM, ages 28-39 years were, recruited to the study. They were divided based on fasting glucose (FBS) level on the glucose tolerance test (GTT): those with FBS less than 90 mg/dl were managed by diet alone; those with FBS greater than 90 mg/dl were immediately started on insulin. The four SBG checks [FBS and 1 hour after each meal (lhpc)] correlated with the continuous glucose monitor with r = 0.91. The women were asked to perform a dipstick for ketones on their urine upon awakening and whenever a meal or snack had been missed. Insulin was initiated when the SBG monitoring indicated that: (1) the FBS was 80 mg/dl whole blood from fingerstick (WBG) or the plasma glucose (PG) greater than 90 mg/dl and/or (2) the lhpc was greater than 140 mg/dl WBG and/or (3) the patient had persistent ketonuria on the prescribed diet which cleared only when the caloric intake was increased to a point which precipitated postprandial hyperglycemia. The prescribed diet was calculated based on body weight to be 30 kcal/kg if the women were between 80 and 120% ideal body weight; or was calculated to be 24 kcal/kg if their weight was greater than 120% ideal body weight. The calories were divided such that 40% was carbohydrate, 20% protein, and 40% fat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212390 TI - Descriptors of alcohol consumption among noninstitutionalized nonalcoholic elderly. AB - This paper describes relationships between reported alcohol consumption and selected sociodemographic and health variables. Two hundred and four men and 367 women aged 60-95 years were examined as part of a nutritional status survey of elderly. Fifty-three percent of men and 44% of women reported drinking at least 2 g of alcohol per week. Men were more likely to drink than women, and the level of alcohol consumption decreased with age. Drinking was positively associated with education (p less than 0.01) and negatively associated with recent medical care (p less than 0.01), history of MI (p less than 0.05), and denture use (p less than 0.05). Among drinkers, reported alcohol intake was higher for subjects less than age 70 (p less than 0.01), males (p less than 0.01), the college educated (p less than 0.01), and smokers (p less than 0.05). Level of alcohol intake was lower for those who had received medical care in the year preceding study participation (p less than 0.05). Identical results were observed for alcohol intake expressed as percent of total calories. Intake ranged from 3.8% of total calories among subjects 80+ years old to 6.2% of total calories among 60-69-year olds. PMID- 2212391 TI - Controlled vitamin C restriction and physical performance in volunteers. AB - A double-blind study on the effects of vitamin C restriction on physical performance was executed with 12 healthy men. During seven weeks of low vitamin C intake six subjects were on a daily diet of regular food products, providing 20% of the Dutch Recommended Dietary Allowances (RDA) for vitamin C (Dutch RDA is 50 mg/day). Other vitamins were supplemented at twice the RDA level. After three weeks of low vitamin intake an additional vitamin C dose of 15 mg/day was provided, resulting in a total intake of 25 mg/day (50% of the Dutch RDA). Six control subjects consumed the same diet supplemented with twice the RDA for all vitamins. In the restriction group blood vitamin C levels decreased significantly (p less than 0.01). Vitamin C restriction had no harmful effects on health, aerobic power (VO2-max), and onset of blood lactate accumulation (OBLA). However, an increased heart rate at OBLA level was observed during the period of low vitamin C intake (p less than 0.05), possibly by interference with either catecholamine or carnitine metabolism. These results suggest that short-term marginal vitamin C deficiency does not affect physical performance in single bouts of intensive exercise. PMID- 2212392 TI - Blood and tissue zinc levels in spontaneously hypertensive rats. AB - Zinc (Zn) determinations were performed on blood plasma and red cells, liver, heart, adrenals, and spleen of spontaneously hypertensive (SHR) and control normotensive (WKY) male rats, 20 weeks of age. SHR revealed higher red cell (p = 2 x 10(-5)) and heart (p = 0.007) Zn levels than WKY rats. The water content of organs was the same in the two strains. When compared with published data, these results suggest an association between high cell Zn levels and hypertension, the meaning of which is briefly discussed. PMID- 2212393 TI - Polyunsaturates, endogenous eicosanoids, and cardiovascular disease. AB - The role of dietary polyunsaturated fats in the prevention of human vascular disease has not been defined, but population and intervention studies have suggested that omega-3 fatty acids (FAs) from marine lipids may have a number of potentially beneficial effects. Eicosanoids are extremely potent autacoids made from polyunsaturated fatty acids and have effects on many vascular parameters, so that the physiological effects of dietary supplementation with polyunsaturated fats are often attributed to alterations in endogenous eicosanoid production. Few studies have attempted to correlate in vivo eicosanoid synthesis and functional effects during such dietary maneuvers, however. This article reviews the relationship between dietary polyunsaturates and endogenous eicosanoid synthesis in man, with particular emphasis on recent studies of the effects of omega-3 FAs. Data on omega-3 FAs and platelet-vascular interactions, blood pressure, and vascular reactivity in human subjects are also summarized, with interpretation of recent work addressing a number of controversial points. A discussion of the significance and future direction of such investigations concludes that further clinical trials in selected patient groups are warranted. PMID- 2212394 TI - The comparative effects of n-3 and n-6 polyunsaturated fatty acids on plasma fibrinogen levels: a controlled clinical trial in hypertriglyceridemic subjects. AB - It has previously been shown that fish oil supplementation, compared to olive oil, reduces plasma fibrinogen. Presented here are the results of a randomized, double-blind, crossover controlled trail that compared the effects of dietary n-3 and n-6 fatty acid supplementation on plasma fibrinogen levels in 10 patients with hyperlipoproteinemia types IIb or IV. Plasma fibrinogen levels showed statistically significant reductions during both the fish oil and corn oil treatment periods. Other variables related to hemostasis which showed no significant changes from baseline included tissue plasminogen activator activity and inhibitor, protein C antigen, antithrombin III activity, bleeding time, and platelet counts. These data confirm the two previous reports that fish oil supplementation is associated with reductions in plasma fibrinogen levels, thereby modifying a potential nonlipid risk factor for cardiovascular disease. Unlike previous reports, however, n-6 polyunsaturated fatty acids were also associated with significant reductions in fibrinogen levels. Therefore, it is premature to conclude that the fibrinogen-lowering effects of dietary fish oil are unique to n-3 polyunsaturated fatty acids. PMID- 2212396 TI - Effect of supplementation with zinc and other micronutrients on cellular immunity of the elderly. PMID- 2212395 TI - Postnatal changes in serum osteocalcin and parathyroid hormone concentrations. AB - Cord clamping at birth leads to interruption of calcium (Ca) supply to the fetus. After birth, neonatal parathyroid hormone (PTH) secretion appears stimulated by hypocalcemia, with serum PTH increasing after birth and peaking at 24 hours of age. This rise in PTH presumably leads to bone resorption and Ca release. We theorize that bone formation may also be affected and that a serum marker of bone formation, serum osteocalcin (OC) concentrations, will decrease postnatally. OC is synthesized by osteoblasts and its serum concentrations are believed to reflect bone formation. We measured serum ionized Ca (iCa), PTH, and OC in cord blood and at 2 and 24 hours in 26 neonates born after uncomplicated pregnancies, labors, and deliveries. Serum iCa (mg/dl) decreased from 5.79 +/- 0.06 (cord, means +/- SEM) to 5.31 +/- 0.05 (2 hr), then to 4.89 +/- 0.05 (24 hr) (p less than 0.05). Serum PTH (microliter Eq/ml) increased from 35.9 +/- 4.3 (cord) to 41.7 +/- 4.0 (2 hr) (p = 0.1), and to 50.3 +/- 4.6 (24 hr) (p less than 0.01). Serum OC (ng/ml) decreased from 55.1 +/- 10.6 (cord), to 12.4 +/- 4.3 (2 hr) (p less than 0.01), then remained stable at 12.7 +/- 1.9 (24 hr). The change (cord minus 24 hr) in OC correlated inversely with the change in PTH over the first 24 hours of age (r = -0.42. p = 0.03). Therefore, there is a sudden decrease in an index of bone formation (i.e., serum OC) in the first 24 hours of life in which rising serum PTH may have had an impact.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212397 TI - Microparticulate protein in foods. PMID- 2212398 TI - Protein microparticulation: the principle and the process. PMID- 2212399 TI - The quality of microparticulated protein. AB - The purpose of this paper is to describe the effects of microparticulation upon the quality of microparticulated protein products and to confirm that microparticulation does not result in changes in protein structure or quality different from those that occur with cooking. Two products were tested: microparticulated egg white and skim milk proteins and microparticulated whey protein concentrate. Three approaches were used to monitor for changes in amino acid and protein value: amino acid analysis, protein efficiency ratio (PER) bioassay, and both one- and two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. Evaluation of the results of these tests indicates that no significant differences were found when comparing the premix before and after microparticulation. Significant differences also did not occur when the premix was cooked using conventional methods. Collectively, the data provide strong evidence that the protein microparticulation process used to prepare microparticulated protein products (e.g., Simplesse) does not alter the quality or nutritional value of protein in the final products. PMID- 2212401 TI - Nutritional implications of microparticulated protein. AB - Recent technological developments have permitted the large-scale preparation of ingredients enriched with microparticulated proteins (MPP) that can be used to replace much or essentially all of the fat in a variety of traditional, full-fat foods. These include ice cream, salad dressings, mayonnaise and cheese spreads. In this paper we consider the nutritional implications of MPP, beginning with an assessment of the need for a fat-substitute and then the potential impact of MPP on the fat content of applicable foods and on the diet as a whole. Under projected conditions of maximum use of these MPP-containing foods by the consumer, the mean reduction in the fat content of the "current U.S. diet" would be about 14%. Although not dramatic, this represents a significant move in the direction of dietary changes that have been recommended by national and international authorities concerned with diet-health relationships. The risk/benefit ratio associated with inclusion of MPP in the diet is considered to be very high. This new development by the food industry is of considerable scientific interest and of potential practical importance for the nutrition and well-being of our society. PMID- 2212400 TI - Food allergy and the potential allergenicity-antigenicity of microparticulated egg and cow's milk proteins. AB - Approximately 3-4 million Americans experience food allergic reactions at some time in their lives. In the pediatric population, eggs and milk are most frequently implicated in food allergic reactions. The most well-understood adverse reactions to foods are secondary to the development of IgE antibodies to specific food antigens. Once an individual becomes sensitized (i.e., makes specific IgE antibodies), ingestion of the food may lead to a variety of cutaneous, respiratory, and/or gastrointestinal symptoms, and anaphylactic shock. The use of SDS-PAGE and immunoblot analyses with sera from documented food allergic patients provide a very sensitive indicator of the antigenic/allergic composition of various foods. As demonstrated in a study of infant formulas of hydrolyzed cow's milk protein, the absence of demonstrable bands on SDS-PAGE gels and immunoblots correlates with an inability to provoke an allergic response. In addition, it was demonstrated that SDS-PAGE with silver staining could detect protein fractions at a concentration of 50-100 ng/ml, a concentration below which allergic individuals are unlikely to react. These studies confirmed that patients clinically allergic to egg and/or cow's milk possess IgE and IgG antibodies to protein fractions in egg and cow's milk, as well as the microparticulated egg/cow's milk proteins, Simplesse and Beta IL. Compared to egg and cow's milk, there is no evidence that the Simplesse or Beta IL test materials possess any "novel" protein fractions or antigens. In addition, there is no evidence that these microparticulated proteins result in increased immunologic activity, as determined by the intensity of protein band staining.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212402 TI - The sensory properties of products made with microparticulated protein. AB - The use of microparticulation to develop products that can be substituted for all or part of the fat portion of food products necessitates the sensory evaluation of these food products to discover formulations, which deliver appearance, flavor, and texture properties similar to the original full-fat foods. Specific consumer and technical/expert attributes are discussed and related to each other to provide guidelines by which microparticulates can be evaluated alone and in different food systems. PMID- 2212403 TI - Dietary fats: perceptions and preferences. PMID- 2212404 TI - Environmental factors versus genetic determinants of childhood inhalant allergies. PMID- 2212405 TI - Specific immunotherapy in asthma. PMID- 2212406 TI - Enhanced reactive oxygen species metabolism of airspace cells and airway inflammation follow antigen challenge in human asthma. AB - Airflow limitation and airway inflammation follow antigen bronchoprovocation in sensitized individuals. Inflammation likely results from the interplay of several previously demonstrated factors, but the participation and persistence of enhanced reactive oxygen species (ROS) metabolism of airspace cells after antigen challenge have received more limited attention. We studied nine subjects with mild asthma by bronchoalveolar lavage before and 48 (one subject) to 72 (eight subjects) hours after antigen bronchoprovocation and compared airspace cell numbers and types, cell function, and bronchoalveolar lavage fluid protein, albumin, and immunoglobulins. Mild, but significant, airflow limitation persisted at the time of the second lavage. Eosinophil influx was a notable component of the increased airspace cells in postchallenge lavages. Airspace cells demonstrated significantly enhanced ROS metabolism, and total protein, albumin, and IgM levels were higher in postchallenge lavage specimens. Antigen bronchial challenge produces airspace inflammation, which may develop, in part, as a consequence of enhanced ROS metabolism of airspace cells. PMID- 2212408 TI - Repeated exposure of asthmatic airways to inhaled adenosine 5'-monophosphate attenuates bronchoconstriction provoked by exercise. AB - Inhaled adenosine 5'-monophosphate (AMP) induces bronchoconstriction in subjects with asthma, probably caused by histamine release from airway mast cells, and repeated AMP bronchial challenge leads to attenuation of the bronchoconstrictor response. Since exercise-induced bronchoconstriction may be mediated by hypertonic mast cell degranulation, we postulated that repeated AMP bronchial challenge should reduce the response to subsequent exercise challenge. Eight atopic subjects with asthma took part in an unblinded, randomized trial. On the control study day, a treadmill exercise test previously demonstrated to induce a greater than 20% fall in FEV1 was performed. On the AMP study day, three AMP dose response bronchial challenges were performed at 1-hour intervals. Each AMP challenge was continued until either a provocative concentration causing a 20% fall in FEV1 had been achieved (PC20) and the PC20 was calculated, or the maximum concentration of AMP (400 mg/ml) had been administered. After recovery of the FEV1 from AMP challenge, a treadmill exercise test identical to the test on the control study day was performed. On the AMP study day, the geometric mean PC20 was 15.3 (7.9 to 29.5) mg/ml for the first test, and 28.2 (10.7 to 77.4) mg/ml for the third test (not significant). On the control study day, the mean maximum percentage fall in FEV1 after exercise was 28.0% +/- 2.7%, whereas on the AMP study day, it was reduced to 13.0% +/- 4.3% (p less than 0.01). A significant correlation was found between the change in responsiveness to AMP induced by repeated challenge and the attenuation of the subsequent exercise response (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212407 TI - Anaphylaxis during induction of general anesthesia: subsequent evaluation and management. AB - Twenty-seven patients were referred for evaluation of anaphylaxis after induction of general anesthesia (GA) in which thiobarbiturates, muscle relaxants, or antibiotics were administered intravenously. Skin testing by the prick and intracutaneous methods was performed with dilutions of the thiobarbiturates and muscle relaxants; beta-lactam reagents were used in patients who had also received these drugs. No skin test reactivity was noted in 16 normal subjects. Skin tests were positive in 13 patients (thiobarbiturates in five, muscle relaxants in six, and antibiotics in two patients). Two patients were dermatographic and yielded indeterminate skin test results. Eleven of the 27 patients subsequently had GA; all patients received a premedication regimen of prednisone and diphenhydramine. Of three patients with negative skin tests, one experienced an arrhythmia, but no other signs attributable to anaphylaxis were noted. One patient with dermatographism had GA without a reaction. Positive skin tests implicated an agent that was avoided in seven patients; one of these patients experienced delayed urticaria/angioedema after the completion of GA. Thus, no patients developed anaphylaxis during subsequent GA for which agents producing positive skin tests were avoided, and a premedication regimen was used. PMID- 2212409 TI - Aqueous beclomethasone diproprionate nasal spray: regular versus "as required" use in the treatment of seasonal allergic rhinitis. AB - OBJECTIVE: to determine the effect of alternative regimens of nasal steroid administration on symptoms and quality of life. DESIGN: randomized, double-blind, parallel-group comparison. SUBJECTS: sixty ragweed-sensitive adults recruited from participants of previous studies and through media advertising. INTERVENTIONS: 200 micrograms of aqueous beclomethasone diproprionate nasal spray, twice daily, from 1 week before until 1 week after the ragweed-pollen season (regular) or 100 micrograms of the spray, taken as required, up to 400 micrograms daily; troublesome nasal symptoms were treated, in both groups, by increasing the daily dose to 800 micrograms until symptoms were controlled. If this treatment was insufficient, 120 mg of terfenadine, daily, was added. RESULTS: One subject in the "as required"-treated group withdrew with uncontrolled nasal symptoms. In the remaining subjects, sneezing, stuffy nose, and rhinorrhea, measured by a daily diary, were significantly better controlled in the regular-treated group (p less than 0.025). Impairment of quality of life, including sleep disturbance, nonhay fever symptoms, practical problems, and uncomfortable emotions were greater in the as required-treated group (p less than 0.001). Subjects in the regular-treated group required less additional terfenadine (0.27 tablets per subject versus 1.40; p = 0.022). Eye symptoms and eye-drop use were similar in the two treated groups. CONCLUSION: In patients with seasonal allergic rhinitis, regular use of inhaled steroids results in fewer symptoms and better quality of life than when the spray is taken only as required. PMID- 2212411 TI - ELISA for human IgE antibody to subtilisin A (Alcalase): correlation with RAST and skin test results with occupationally exposed individuals. AB - An ELISA was developed to detect specific IgE antibody to the Bacillus subtilis derived proteolytic detergent enzyme, subtilisin A (Alcalase), in sera from exposed detergent workers. Workers in the detergent industry are exposed via inhalation to low levels of the enzyme dust in the presence of detergent dust. Chemically inactivated Alcalase was used as the test antigen. Significant binding of IgE antibody to the immobilized enzyme was detected in the ELISA. The binding of allergic antibody to Alcalase was specifically inhibited in a dose-dependent manner by preincubating sera with 0.1 to 100 micrograms of inactivated Alcalase. Binding of IgE antibody to Alcalase could not be inhibited by two other inactivated bacterial proteases, Savinase and Esperase, derived from different Bacillus species. ELISA and skin test results demonstrated total agreement for 27 of 31 samples (87%), whereas RAST and skin test results demonstrated total agreement for only 24 of 31 samples (77%), indicating that the ELISA was more sensitive than the RAST. We conclude that the ELISA is a sensitive, fast, alternative to the RAST for detection of Alcalase-specific IgE antibody in detergent enzyme-exposed workers. PMID- 2212410 TI - The relationships among shrimp-specific IgG subclass antibodies and immediate adverse reactions to shrimp challenge. AB - High levels of shrimp-specific IgE, in association with a positive prick test, are not always predictive of a positive, immediate response to double-blind, placebo-controlled, food challenge (DBPCFC) with shrimp. The observation that shrimp-sensitive individuals in general have increased levels of circulating shrimp-specific IgG is of interest because antigen/allergen-specific IgG subclasses have been associated with adverse reactions to foods. Therefore, this current study measured shrimp-specific IgG subclass and IgE antibodies in 31 individuals with histories of immediate, adverse reactions to shrimp immediately before DBPCFC and 20 shrimp-tolerant subjects. Individuals with a history of shrimp sensitivity had significantly raised shrimp-specific IgG2 and IgG4 compared to shrimp-tolerant individuals. Challenge-positive subjects were distinguished from subjects with negative or equivocal responses by an increased IgG2 (p less than or equal to 0.001). Specific IgG4 was not raised (p less than or equal to 0.065). These studies indicate that some shrimp-specific IgG subclass levels are increased in shrimp-sensitive subjects. However, none of the subclass responses were significantly predictive of a positive response to DBPCFC and therefore were not diagnostic of shrimp intolerance. PMID- 2212412 TI - Increased serum IgE and increased prevalence of eosinophilia in 9-year-old children of smoking parents. AB - We studied the relationship of serum IgE levels and eosinophil counts with passive smoking in 9-year-old, nonselected children from three Italian towns near Rome. Male children of smoking parents had a significantly higher total count and percentage of eosinophils (p = 0.008) and higher IgE levels (p = 0.01) than male children of nonsmoking parents. Prevalence of eosinophilia (defined as greater than or equal to 4% of total white blood cell count) was significantly correlated with the number of cigarettes smoked by parents among boys (p = 0.003) but not among girls (p = 0.20). There was a significant trend (p = 0.008) for prevalence of eosinophilia to increase with increasing levels of serum IgE. For any given level of serum IgE, the frequency of eosinophilia was higher among children of smoking parents than among children of nonsmoking parents. When parental smoking was studied in a multivariable analysis and after controlling for the other variable, it was still significantly associated with eosinophilia in the children of these smoking parents but not with serum IgE levels. We conclude that parental smoking is associated with a significant enhancement of the expression of the most important markers of allergic sensitization in the children of smoking parents. This is particularly evident for boys and may explain, at least in part, the increased frequency of respiratory symptoms in children of smoking parents. PMID- 2212413 TI - Nonatopic rhinitis and bronchitis with eosinophilia syndrome. PMID- 2212415 TI - Decreased skin response to intradermal platelet-activating factor (PAF-acether) in cancer patients. PMID- 2212414 TI - Severe multisystem disease caused by trimethoprim-sulfamethoxazole: possible role of an in vitro lymphocyte assay. PMID- 2212416 TI - Cat-allergen sensitivity. PMID- 2212417 TI - Workshop on experimental methodology for clinical studies of adverse reactions to foods and food additives. PMID- 2212418 TI - Weight loss study provokes comment. PMID- 2212419 TI - Bringing the cholesterol message to the public: dietitians must be proactive in nutrition counseling. PMID- 2212420 TI - Health and nutrition survey in a group of urban homeless adults. AB - Homeless persons eat foods from municipal and privately run shelters, fast-food restaurants, delicatessens, and garbage bins. Data on the adequacy of the diets and the nutritional status of homeless persons are sparse. Therefore, we surveyed the nutritional adequacy of the dietary intake, the quality of shelter meals, and objective clinical parameters indicative of nutritional status in a heterogeneous group of urban homeless persons. The group comprised mentally ill persons, alcohol and illicit drug users, and temporarily unemployed persons. Although 86 of the 96 subjects (90%) in our survey reported that they obtained enough to eat, a low dietary adequacy score, which was based on the basic four food groups, of 10.7 (norm = 16) indicated that the quality of their diets was inadequate. Shelter meals and diet records showed a high level of saturated fat and cholesterol. Serum cholesterol levels above the desirable limit of 5.17 mmol/L (200 mg) were observed in 79 subjects (82%). In addition to a prevalence of hypertension and obesity (observed in 37 subjects [39%], these homeless persons were at high risk for development of or worsening of cardiovascular disease. We conclude that homeless persons who obtain meals at shelters are getting enough to eat. However, the shelter meals should be modified to meet the nutritional needs and dietary prescriptions of the large number of clients who suffer from various health disorders. PMID- 2212421 TI - Nutrition care planning: comparison of the skills of dietitians, interns, and students. AB - A written case study--or patient management problem--was used to examine how the nutrition care planning process is influenced by increasing clinical experience. The sample consisted of 45 students in diet therapy courses, 46 dietetic interns, and 44 experienced clinical or generalist dietitians. The patient management problem tested data gathering, with sections containing information needed to assess nutritional status, and nutrition care planning, in which subjects identified and evaluated problems and selected short- and long-term goals. Performance was scored by comparing subjects' answers with those of five dietetic experts. Dietitians scored highest and students scored lowest on efficiency of data gathering. Dietitians and interns scored higher than students on proficiency of data gathering and nutrition care planning. Overall, dietitians and interns performed better than students. Only in tasks requiring the highest levels of information processing and/or confidence in clinical judgment were differences between dietitians and interns consistently found. These findings demonstrate that basic nutrition care planning skills are acquired during dietetic internships, but advanced skills are added with clinical experience. PMID- 2212422 TI - The effect of education on foodservice manager job satisfaction. AB - We conducted a study to determine whether educational background (field of study and level of education) was related to the job satisfaction of foodservice managers. The Index of Organizational Reactions Questionnaire was used to measure specific components of job satisfaction based on a five-point Likert-style scale (1 = low satisfaction, 3 = moderate satisfaction, and 5 = high satisfaction). Questionnaires were mailed to the entire population of 256 foodservice managers employed in college and university dining facilities of a regional division of a major foodservice company in the northeastern United States. Names, titles, positions, and addresses of the managers were obtained from the company's human resources department. Analysis of data was done through computation of the point biserial correlation coefficient and the rank order correlation coefficient. Managers who responded to the questionnaire (74.6%) indicated moderate overall job satisfaction (mean = 3.42 on a 5-point scale). Of the respondents, 44% had an educational background in foodservice; these respondents had lower overall job satisfaction than did those having no education/training in foodservice. Both groups were most satisfied with the job components of supervision, type of work, and relationship with coworkers. Both groups were least satisfied with pay and benefits, company identification, and amount of work. A significant (p less than .01) positive relationship was found between educational field of study and job satisfaction, and a significant (p less than .001) negative relationship was found between educational level (i.e., degree[s] earned) and job satisfaction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212423 TI - Improved accuracy of estimating food quantities up to 4 weeks after training. AB - Subjects from a large introductory nutrition course were divided into two groups, one that received training on estimating food quantities and one that received no instruction. Training consisted of 10-minute sessions during which subjects passed around and viewed 10 food models labeled with their respective quantities. The trained subjects estimated quantities of six real foods at one of three points in time: immediately after training, 1 week later, or 4 weeks later. Untrained subjects estimated quantities of the same six foods. For all foods combined, trained subjects gave significantly better estimates than untrained subjects, whether estimates were made immediately after training, 1 week later, or 4 weeks later. The estimates of the trained subjects on the day of training and 1 week later were not significantly different, but both were significantly better than estimates made 4 weeks later. In regard to individual food items, trained subjects estimating immediately or 1 week later were always more accurate than untrained subjects. Effects of training disappeared by week 4 for three of the six foods. These results support the use of training, with food models, to improve an individual's ability to estimate food quantities accurately and indicate that the impact of such training lasts for at least 1 week and can last up to 4 weeks. The findings imply that training with periodic reviews may be necessary in a clinical setting to ensure that patients estimate their food consumption accurately. PMID- 2212424 TI - Promoting adherence to low-fat, low-cholesterol diets: review and recommendations. AB - Evidence that lowering blood cholesterol levels reduces risk of coronary heart disease has prompted widespread recommendations that hyperlipidemic individuals undergo dietary therapy. However, the extent to which people can adopt and maintain diets to lower lipids is unclear. In our article, we review what is currently known regarding adherence to low-fat diets and present an approach to dietary counseling for lowering cholesterol that incorporates elements of behavioral self-management and social learning theory. We discuss specific recommendations for counseling hyperlipidemic patients based on the Dietary Alternatives Study. Recommendations include providing patients with an adequate knowledge base to make dietary changes, using goal setting and self-monitoring to help patients initiate dietary changes, enlisting support from the patient's family, and enhancing self-efficacy to promote long-term dietary maintenance. PMID- 2212425 TI - Nutrition education and counseling: knowledge and skill levels expected by dietetic internship directors. AB - Development of nutrition education and counseling skills is important in the educational preparation of dietitians. A national survey of dietetic internship directors was conducted to determine competency levels expected of students at the start of an internship, internship training given, and further preparation students need in 32 knowledge/skills areas deemed essential for delivery of nutrition education and counseling services. Completed questionnaires were received from 66 of 102 (65%) internship directors surveyed. The majority of directors expected only basic preparation for group nutrition education and individual counseling knowledge/skills areas. Internship training in nutrition education competencies was "moderate" to "extensive," whereas preparation in nutrition counseling competencies was more likely to be "extensive." Directors perceived the internship to provide adequate preparation in all but the advanced practice skills, such as behavior modification and motivational strategies, for which further preparation was recommended. The majority of internship directors reported that more than 25% of the intern practice experience was in patient counseling, with less experience in group instruction. Implications for undergraduate dietetic education are discussed in relation to internship directors' expectations as well as to present and future trends in the dietetic profession. PMID- 2212427 TI - Cardiovascular risk changes in a work-site health promotion program. PMID- 2212426 TI - Capacity of state health agencies to meet nutrition objectives in maternal and child health. AB - Public health nutritionists in 54 official state health agencies were surveyed in 1987 to determine to what extent they were prepared to implement the Model State Nutrition Objectives developed by the Association of State and Territorial Public Health Nutrition Directors. Objectives related to services to the maternal and child health (MCH) population were the focus of one part of the survey. One half of all states have plans for nutrition services integrated into their state MCH plans. More than 75% of state agencies collect data on the nutritional status of pregnant and lactating women, infants, and preschool children. Fewer than half collect data on dietary intake patterns or nutrition knowledge. Thirty-one agencies reported a formal quality assurance program for one or more subsets of the MCH population. At least 75% of all states provide dietary intake recommendations, screening and assessment protocols, and policies concerning referrals to maternal and infant health programs. State health agencies are already involved in activities that will facilitate adoption of the model state nutrition objectives. PMID- 2212428 TI - Sources of fat, fatty acids, and cholesterol in the diets of adolescents. PMID- 2212429 TI - Comparison of a food frequency questionnaire and a 3-day diet record. PMID- 2212430 TI - Effects of Ramadan fasting on plasma uric acid and body weight in healthy men. PMID- 2212431 TI - Position of the American Dietetic Association: domestic hunger and inadequate access to food. PMID- 2212432 TI - President's page: Rx for change. PMID- 2212433 TI - Margaret A. Lavery wins Huddleson Award. PMID- 2212434 TI - Measurement of height in the elderly. AB - Height is an essential variable when assessing renal clearance, nutritional status, and absorption. Standard methods of estimating height are impractical in the nonambulant. One hundred sixty-five elderly inpatients were studied. Total standing height, knee-to-floor height, and tibial length were measured. Total arm, upper arm, and forearm measurements were obtained in both erect and supine positions. Measured height correlated best with supine total arm length (R2 = .69), knee-to-floor height (R2 = .63), and erect forearm length (R2 = .61). A nomogram relating both supine total arm length and knee-to-floor height with the patient's measured height has been prepared. PMID- 2212436 TI - An external urine collection device for incontinent women. Evaluation of long term use. AB - Urinary incontinence is common in aged women, may precipitate nursing home admission, and may prompt use of a urine collection device, usually an indwelling urethral catheter. The safety and efficacy of a new external urine collection device for women that is affixed to the perineum by an adhesive developed for ostomy bags was evaluated. Applied to 26 aged women, 78% of 2,264 devices were leak-free for 24 hours and 49% for 48 hours. The incidence of new bacteriuria was less than half that found in our earlier studies of long-term urethral catheters in the same institution. Perineal erythema was infrequent and preexisting decubitus ulcers improved or did not change. Four patients were withdrawn, one each because of periurethral itching, diminished urine output, recurrent wetness, and fracture of the proximal femur associated with severe osteoporosis. This device may offer an alternative to urethral catheters for management of urinary incontinence but should not be used on women with urine retention and should be used with care on women with severe osteoporosis. Controlled trials must determine effects upon bacteriologic complications and health-care costs. PMID- 2212435 TI - Do-not-resuscitate orders in an extended-care study group. AB - We examined the charts of 911 nursing home patients in Hennepin County, Minnesota, to determine the prevalence of written do-not-resuscitate (DNR) orders. Information regarding demographic characteristics, and whether a surrogate decisionmaker was available and participated in the decision, was also collected. Twenty-seven percent of patients had DNR orders. Ninety percent of all patients had potentially available surrogate decisionmakers. However, for 31% of patients with DNR orders, there was no documentation of patient or surrogate participation in the DNR decision. Univariate analysis identified female sex; increased age, level of care (skilled versus intermediate), presence of a potential surrogate decisionmaker, and increasing length of time since nursing home admission as factors associated with presence of DNR orders. When a logistic regression model was used, increased age, increased length of time since nursing home admission, skilled versus intermediate level of care, and presence of a surrogate decisionmaker were independently associated with presence of DNR status. Several variables are independently associated with written DNR orders; their relationship to the factors physicians use in decision making requires further study. PMID- 2212438 TI - Bilateral fractures of the humeral head related to myoclonic jerks and use of a tray table for positioning. PMID- 2212437 TI - Lateral chest roentgenograms in debilitated nursing home residents. PMID- 2212439 TI - A proinflammatory mediator with potential relevance in aging. PMID- 2212440 TI - Resuscitating the nursing home resident. Futility and pseudofutility. PMID- 2212441 TI - On getting older and getting younger again. PMID- 2212442 TI - Geriatric rehabilitation. AGS Public Policy Committee. PMID- 2212443 TI - Expanded access to rehabilitation services for older people. An urgent need. PMID- 2212444 TI - CPR in nursing homes. PMID- 2212445 TI - To screen or not to screen? PMID- 2212446 TI - What do citations mean? PMID- 2212447 TI - Dementing disease in a married couple. PMID- 2212448 TI - "The trajectory of dying": commentary and response. PMID- 2212449 TI - Taking to bed. Rapid functional decline in an independently mobile older population living in an intermediate-care facility. AB - The objective of this study was to determine the incidence and selected clinical outcomes of taking to bed among a population of independently ambulating older individuals. It was designed as a retrospective case series and was conducted in the intermediate-care facility of a not-for-profit, teaching nursing home. Our study group was composed of individuals over 65 years of age who became bed bound. Thirty-six taking-to-bed episodes occurred in 36 individuals during one calendar year, giving an incidence of 13 per 1,000 resident-months (95% CI, 4 to 23 per 1,000). Twelve of the 36 died within 3 months, and 17 within 6 months, but almost all who survived regained ambulation. Survival was significantly shorter for the five without localizing symptoms (P less than .05). Orthopedic, neurologic, psychiatric, and iatrogenic conditions were most commonly identified as concurrent medical events. Almost half who took to bed had multiple concurrent medical events, and these residents were more likely to present without localizing symptoms (P less than .05). Twenty-one (58%) of the episodes occurred after a fall. The incidence of taking to bed in this population indicates that clinicians caring for older persons should be alert to its occurrence. The dramatic decline in mobility deserves careful assessment because it initiated a period of relatively rapid change in the health careers of the individuals we studied: almost half died within 6 months, but nearly all who survived regained ambulation. Those without localizing symptoms may have more complex interacting medical problems and a worse prognosis. PMID- 2212450 TI - Absence of nocturnal fall in blood pressure in elderly persons with Alzheimer type dementia. AB - Circadian changes of the blood pressure and heart rate in elderly normotensive bedridden patients with severe dementia of the Alzheimer type (group D) were compared with those in elderly normotensive bedridden patients without dementia (group R), normotensive subjects with normal daily activity (group N), and hypertensive patients with normal daily activity (group H). In groups R, N, and H, the blood pressure increased in the afternoon and decreased at midnight; in group D, however, although it increased in the afternoon, it did not decrease at night. The circadian changes of the heart rate were similar in all four groups, showing maxima in the afternoon and minima at midnight. Thus, a specific alteration was found in the circadian rhythm of the blood pressure in patients with Alzheimer-type dementia. PMID- 2212451 TI - Prevalence and characteristics of multiple analgesic drug use in an elderly study group. AB - With few exceptions, use of multiple analgesic drugs achieves dubious increases in analgesia while placing elders at increased risk of the many potential adverse effects of analgesic drugs. The potential for duplication of analgesic therapy among the elderly is great due to prevalent painful chronic conditions and the variety of prescription and nonprescription analgesic remedies available. The prevalence of multiple analgesic product use and patterns of concurrent use of different analgesic categories was investigated in a geographically defined population of persons 65 years of age and older. The demographic characteristics of users of multiple analgesic drug products were examined, as were their smoking status, alcohol use, lifetime history rates of major illnesses, physical functioning, pain experiences, memory performance, and depressive symptoms. A substantial proportion of analgesic users reported taking multiple products in the preceding 2 weeks (14.4% of female and 10.5% of male analgesic users). Men who reported pain in the preceding year were more likely to use multiple analgesic products. Women who experienced pain or limited physical functioning, or who had higher depressive symptom scores or a life-time history of ulcers were most likely to use multiple analgesic products. Thus, although some users of multiple analgesic products reported significant pain, several other factors were shown to be related to the phenomenon of multiple use. PMID- 2212453 TI - Fever of unknown origin in an elderly patient diagnosed at postmortem examination as multifocal angiofollicular lymph node hyperplasia. PMID- 2212452 TI - Imidazole salicylate versus piroxicam in the treatment of arthrosis in elderly patients. A double-blind clinical and endoscopic trial. AB - The clinical efficacy and gastroduodenal tolerability of imidazole salicylate (imidazole 2-hydroxybenzoate, ITF 182), a new synthetic drug with an anti inflammatory action, was evaluated endoscopically in comparison with those of piroxicam in elderly patients suffering from osteoarthrosis. Of the 41 patients entering the trial, only 38 completed the protocol (6 men and 32 women; mean age, 71; range, 65-80 years). After upper gastrointestinal endoscopy for the purpose of excluding gastric and duodenal mucosal lesions, the patients were allocated at random, according to a double-blind, double-dummy protocol, to treatment either with imidazole salicylate 750 mg three times daily or with piroxicam 20 mg once daily for a period of 4 weeks. Imidazole salicylate proved active in controlling a number of the pain symptoms caused by arthrosis, although its efficacy was inferior to that of piroxicam. Grade 2 gastric mucosal lesions were detected in 1 of 20 patients (5%) treated with imidazole salicylate; lesions corresponding to grades 2, 3, and 4 were found in 6 of 18 (33%) of those treated with piroxicam (P = .034). Painful dyspepsia was reported by 15% of the patients in the imidazole salicylate group and by 28% of those in the piroxicam group. On the basis of these results and under the experimental conditions adopted in this trial, the authors concluded that imidazole salicylate is characterized by good gastric tolerability and can thus be used in the treatment of rheumatic diseases in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212454 TI - Short-term variability of measures of physical function in older people. AB - Self reported physical function was assessed in telephone interviews approximately 3 weeks apart for a sample of 193 persons aged 69 or older. Three measures of physical function were used: a modified Activities of Daily Living scale, three items proposed by Rosow and Breslau, and five items from among those used by Nagi. Agreement between first and second interviews was very good; most subjects reported no impairment in function at either interview. Among those who reported some impairment, the degree of limitation within the specific activities reported as limited and the total number of activities with any degree of limitation agreed exactly for most and within one level for almost all subjects. There was no evidence to suggest that age or cognitive impairment affected the variability of the responses, and reported declines and improvements in function were about equally common. PMID- 2212455 TI - Dietary preference for sweet foods in patients with dementia. AB - Using a telephone survey, patients with probable Alzheimer's disease (n = 31) and vascular dementia (n = 14) were compared with elderly normal controls (n = 43) in preferences for different foods. Patients with Alzheimer's disease had a greater preference than normal controls for relatively high-fat, sweet foods and for high sugar, low-fat foods, but did not significantly differ in preference for other foods, including those high in complex carbohydrates and protein. Vascular dementia patients showed a similar pattern, not significantly different from that for Alzheimer's patients. Results did not consistently support a hypothesis that increased sweet preference is a nonspecific form of disinhibited behavior related to declining mental status, nor was a hypothesis relating sweet preference to serotonin activity within the brain consistently supported. Results provide preliminary evidence that craving for sweet food may be a significant part of the clinical syndrome of dementia, but further research is needed to delineate the psychological and biological mechanisms accounting for it. PMID- 2212456 TI - The development of western optometry--a case for history. PMID- 2212457 TI - The specialty lens cycle. PMID- 2212459 TI - Comments on "more research". PMID- 2212458 TI - Vision field assessment. PMID- 2212460 TI - A comparison of cycloplegic refraction to the near retinoscopy technique for refractive error determination. AB - The near retinoscopy technique of refractive error determination was compared to the standard method of cycloplegic refraction using 10 "infants" (3-12 months of age) and 10 "children" (32-109 months of age). There was a significant difference between the techniques for both sphere and cylinder power. Although there was no interaction of refractive technique and age group, the difference between near retinoscopy and cycloplegic refractive error tended to be larger for infants than for children. No significant difference was found when the average refractive values were compared for monocular or binocular conditions and no significant effect was found for either gender or laterality (right versus left eye). Based on these findings, it is suggested that caution be used in substituting the near retinoscopy technique for cycloplegic refraction even utilizing a "correction" factor for the dioptric difference between techniques. PMID- 2212461 TI - A survey of Missouri doctors of optometry who have not been certified to use therapeutic pharmaceutical agents. AB - This study surveyed all optometrists in Missouri who had not been certified to use TPAs to determine their attitudes regarding this recent expansion in the legally permitted scope of practice. About half of those who were DPA certified doctors plan to seek TPA certification, however only about a third of those without DPA certification plan on doing so. The most common reason given by DPA certified optometrists for not obtaining TPA certification was lack of time to meet the educational requirements. Most non-DPA certified doctors did not plan to seek TPA credentials because of impending retirement. Few of either group felt that their interactions with ophthalmologists had been adversely affected by the change in the optometric practice act. PMID- 2212462 TI - Thyroid eye disease: review and case reports. AB - Thyroid eye disease or Graves' orbitopathy is the most common orbital pathology occurring in the general population. It is usually a self-limited condition with severe disease occurring in approximately 2-7 percent of cases. Various symptoms and signs are presented along with specific medical and surgical treatment modalities. Differential diagnosis is emphasized including examination procedures. The primary eye care optometrist is well qualified to treat the symptomatology and follow patients for compressive optic neuropathy during the disease process. Three case reports are introduced to aid in enhancing the information presented. PMID- 2212463 TI - Nonsurgical management of blepharoptosis. AB - Ptosis of one or both eyelids is a problem which affects a small, but nonetheless significant, portion of the population. Ptosis can be managed in a variety of ways, all of which can usually bring about a resolution of the problem to varying degrees of satisfaction. Two patients who were helped significantly through the use of two non-invasive techniques are presented here. Both patients, somewhat handicapped by the ptosis, were able to return to a more normal daily routine as a result of the therapy employed. The etiology of blepharoptosis and its workup are briefly reviewed. PMID- 2212464 TI - Informed consent for presbyopic contact lens patients. AB - The doctrine of informed consent requires that health care practitioners provide each patient with sufficient information about a proposed treatment so that the patient can make a knowing, willing and intelligent decision about the recommended treatment. The need for a thorough, well documented informed consent is especially important when prescribing monovision or bifocal contact lenses for presbyopic patients because of the relatively low success rate and possible associated vision compromise. Patients should be advised of the alternatives available and provided with a supplemental or alternative correction which will optimize the patient's vision for driving and other potentially hazardous activities. An example of an informed consent document that could be used to record the warnings and advice given to presbyopic contact lens patients is included. Failure to obtain the patient's informed consent and properly document it can be a major source of liability in contact lens practice. Use of informed consent documents such as the one described in this paper can minimize this possibility. PMID- 2212466 TI - A high-performance liquid chromatography method for separation of purine bases, nucleosides and ureides: application to studies on purine catabolism in higher plants. AB - Mixtures of purine nucleotides, nucleosides, nucleobases, uric acid, allantoin and allantoic acid were fractionated by high-performance liquid chromatography on a polyvinyl alcohol gel column, Asahipak GS-320H, with isocratic elution by sodium phosphate. Application of this system to the determination of the sizes of cellular pools of purine derivatives in plant cells and of the activity of related enzymes, as well as to the purification of enzymatically synthesized radioactive compounds, is described. PMID- 2212465 TI - Purification of calf thymus RNA polymerase II for in vitro transcription studies. AB - A procedure for the purification of a large amount of RNA polymerase II (RNAP II) from calf thymus is described. This procedure results in an approximately 1400 fold purification with 40% yield of enzyme in 60 h. The partially purified enzyme is highly suitable for in vitro transcription studies in a cell-free system utilizing HeLa S-100. This method for RNAP II purification would find significant applications in in vitro studies for the analysis of factors modulating eukaryotic transcription. PMID- 2212467 TI - Elimination of non-specific binding in western blots from non-reducing gels. AB - The reaction of some antibodies with Western blots of protein shows strong non specific binding especially at a region that corresponds to about 70-90 kDa. This binding is independent of protein concentration. Further analysis indicated that the factor responsible for the non-specific binding is 2-mercaptoethanol in the gel sample buffer. Gel electrophoresis of total tissue homogenates in the absence of this reducing agent resulted in dramatic elimination of the non-specific background binding without affecting the mobility of the two proteins we studied. PMID- 2212468 TI - Measurement of non-specific binding by parallel or consecutive incubation procedures in receptor homogenates following tissue disintegrations by sonification. AB - It was demonstrated with 125I-labeled insulin and homogenates of human placenta that the energy and duration of tissue disintegration by sonification markedly affected the extent and reproducibility of binding. If the non-specific binding was determined by consecutive incubation on identical samples, as was the total binding, the data obtained were more reproducible and closer to the affinity values and number of receptors that had been obtained on isolated trophoblast membranes when compared to experiments in which the non-specific binding was measured on different samples than for the total binding. On isolated membranes, the results were almost unaffected by the method of measuring non-specific binding. Therefore, we suggest that total and non-specific binding should be measured consecutively on identical samples if only small amounts of homogenized tissue are available. PMID- 2212469 TI - First meeting of the Italian Society for Neurovegetative Research. Montecatini Terme, Italy, 1-3 June 1989. Proceedings. PMID- 2212471 TI - The neural regulation of circulation explored in the frequency domain. PMID- 2212470 TI - Bradycardia and long QT interval in neonate rats with delayed cardiac sympathetic innervation. PMID- 2212472 TI - Influence of nerve plexus on distensibility and spontaneous activity in the isolated guinea pig gallbladder. PMID- 2212473 TI - Urinary bladder innervation in experimental diabetes. PMID- 2212474 TI - Sympathetic activation during treadmill exercise in the conscious dog: assessment with spectral analysis of heart period and systolic pressure variabilities. AB - We studied in seven conscious dogs the dynamic rearrangements in neural control of heart rate and left ventricular pressure during treadmill exercise as assessed by spectral analysis. The presence, at rest, of a major high-frequency component (HF), an indicator of vagal tone, was reverted during exercise to a major low frequency component (LF), an indicator of sympathetic activation. These changes were blunted by chronic beta and alpha 1 adrenergic receptor blockade. PMID- 2212476 TI - Interstitial cells of Cajal and slow wave generation in canine colonic circular muscle. PMID- 2212475 TI - Autonomic nervous system and microcirculation in diabetes. AB - In order to evaluate the occurrence of sympathetic impairment of skin microvascular control in diabetes, we evaluated the spectral analysis of forearm skin laser-Doppler fluctuations in nine insulin-dependent diabetic subjects and in 21 controls of similar age. Low-frequency oscillations (around 0.1 Hz) were significantly lower in diabetics than in controls (2.333 +/- 0.340 (mean +/- SEM) units vs. 3.486 +/- 0.093 units, P less than 0.001), whereas no significant differences were found between the two groups regarding high-frequency respiration-related oscillations. These results suggest that the loss of rhythmicity in diabetic subjects is selectively related to low-frequency oscillations, mostly under sympathetic control, and is likely to be dependent on autonomic abnormality. PMID- 2212477 TI - Vasovagal reactions induced by head-up tilt and tests of vagal cardiac function. AB - The vagal cardiac activity was compared in two groups of patients with a history of syncope. Sixty-one patients (Group A) experienced vasovagal reactions induced by head-up tilt, 61 sex and age-matched patients (Group B) did not. No significant differences in vagal cardiac activity between two groups were found. Group A was further subdivided into two subgroups: A1 (14 patients) with stronger, and A2 (47 patients) with smaller cardioinhibition. Again, vagal cardiac activity was not different between two subgroups. Thus, the baseline vagal cardiac activity ('tone') seemed not to be helpful in predicting the susceptibility to vasovagal orthostatic syncope and in discriminating the patients with stronger cardioinhibition. PMID- 2212478 TI - Autonomic neuropathy and secondary hyperparathyroidism in uremia. AB - To evaluate the relationship between autonomic neuropathy, and biochemical and radiological parameters of secondary hyperparathyroidism, we examined 19 predialysis and 24 hemodialysis non-diabetic uremic patients. Autonomic neuropathy was assessed using four cardiovascular tests. Ten predialysis and 15 hemodialysis patients showed abnormalities in one or more autonomic tests. Ca, Ca2+, P, alkaline phosphatase, immunoreactive parathyroid hormone and osteocalcin did not significantly differ in uremic patients with and without abnormal autonomic test results. Radiological markers of hyperparathyroidism such as acro osteolysis (score A) and subperiosteal resorption (score B) were more common in patients with abnormalities in autonomic tests than in patients without. When predialysis and hemodialysis patients were considered separately, the correlation between score A, score B and autonomic neuropathy was confirmed only in hemodialysis patients. In conclusion, autonomic neuropathy is not related to biochemical parameters of hyperparathyroidism, while it appears correlated with radiological signs of osteodystrophy, suggesting a possible pathogenetic link between autonomic neuropathy and secondary hyperparathyroidism. PMID- 2212479 TI - Effects of arterial infusions of adenosine 5'-triphosphate (ATP) and vasoactive intestinal polypeptide (VIP) on vagal excitatory motor responses in the rabbit stomach 'in vivo'. AB - In the rabbit stomach 'in vivo' adenosine and adenosine 5'-triphosphate depressed the contractile activity elicited by vagal stimulation. The order of potency was ATP greater than adenosine. Only ATP completely blocked the excitatory motor responses. Vasoactive intestinal polypeptide injected close-arterially scarcely affected the vagal contractile activity of the stomach. PMID- 2212480 TI - Postnatal development of cardiac innervation and susceptibility to malignant arrhythmias in the dog. PMID- 2212481 TI - The role of chemosensitive muscle receptors in cardiorespiratory regulation during exercise. AB - Several possible mechanisms leading to the cardiorespiratory adjustments to muscular exercise can be considered. Activation of the cardiovascular and respiratory centers may result from: (1) direct or reflex action of circulating metabolites (humoral control); (2) cortical influxes (central drive); (3) nervous impulses from receptors in the contracting muscles (peripheral drive). Information presently available focuses most of the interest upon the muscular drive. Our studies on anesthetized animals (rabbits, dogs) have demonstrated that different types of exercise (dynamic and static) produce two different types of adjustments reflexly elicited by activation of sensory endings of somatic afferents in muscles. Dynamic exercise produces a vasodilatory effect with a decrease in blood pressure and heart rate and an increase in breathing frequency; static exercise provokes an increase in blood pressure, heart rate and depth of breathing. These two patterns of adjustments to exercise are also reproducible, in anesthetized animals, by injecting chemical substances into muscular arteries. Injections of bradykinin, K+ ions and acid solutions evoke cardiorespiratory responses analogous to those produced by dynamic contractions; injections of hypertonic NaCl or glucose evoke an excitatory pattern closely similar to that elicited by isometric contractions. These research studies lead to the hypothesis that two functionally distinct types of chemosensitive receptors (K and P) exist in the skeletal muscles which are activated in proportionally different measures during different types of muscular activity, thus evoking coordinated changes in the cardiovascular and respiratory functions. These studies also strongly support the important role of the peripheral reflex mechanism in governing the circulatory and respiratory systems to perfectly match cardiorespiratory changes to the muscular metabolic needs during exercise. PMID- 2212482 TI - Organization of the tonically active pathways through the superior cervical ganglion of the rabbit. AB - Responses of the neurons of the rabbit superior cervical ganglion to stimulation of the fascicles of preganglionic nerve fibres dissected from the cervical sympathetic trunk, and tonic activity of these neurons were recorded with intracellular electrodes in vitro and in vivo, respectively. It was found that on average 8.5 +/- 1.2 preganglionic fibres converge on each ganglion cell. In each preparation a single input spike could be evoked in a ganglion cell by stimulation of only one of all tested fascicles. The interspike intervals for single and multiple preganglionic inputs in tonic activity of ganglion neurons displayed Gaussian and Poisson distributions, respectively. The frequencies of spikes showing a Gaussian distribution correspond in most cases to pulse and respiratory frequencies. These data suggest that (1) single input is formed by a single preganglionic fibre which evokes EPSP of an amplitude high enough to trigger a postsynaptic spike, and that (2) regular activity of the ganglion neuron triggered by single input is probably due to a regular afferent drive. A cross-correlation analysis between the intracellular tonic activity and the tonic activity simultaneously recorded from the postganglionic nerve was made. The results of the analysis were compared with those obtained when intracellular spikes were evoked by stimulation of one particular neuron. From this comparison it has been concluded that about 100 ganglion cells, on the average, discharge synchronously within the 20-ms range during their tonic activity. PMID- 2212483 TI - Heart rate spectral analysis for assessing autonomic regulation in diabetic patients. AB - Spectral analysis of the R-R variability signal has been used for assessing the autonomic regulation of heart rate in control subjects and in diabetic patients affected by autonomic neuropathy. Modifications of the parasympathetic sympathetic balance following postural changes, as observed in normal subjects, were not significant in autonomic patients. In addition, the overall reduction of power occurring in diabetics at all frequencies indicates the impairment of both autonomic components. PMID- 2212484 TI - Cardiopulmonary receptors and coronary circulation. PMID- 2212485 TI - Uraemic autonomic neuropathy. AB - Symptoms of uraemic autonomic neuropathy are often vague and aspecific. A correct diagnosis of autonomic dysfunction is possible by using several simple and non invasive tests of parasympathetic and sympathetic control of the cardiovascular system. A defective regulation of the heart rate, due mostly to an afferent lesion, is more common than damage of reflex blood pressure control. The former appears isolated in 14 to 34% of uraemics on haemodialysis and combined to the latter in 18 to 26%. Contradictory results are reported about influence of intermittent haemodialysis, continuous ambulatory peritoneal dialysis and kidney transplantation on disturbed autonomic nervous system. Pathogenesis of uraemic autonomic neuropathy remains unknown and some mechanisms are only putative. PMID- 2212486 TI - Neural control of human skin blood flow. AB - The paper reviews recent studies on neural control of skin blood flow, with special emphasis on the interaction between vasoconstrictor and vasodilator mechanisms. Intraneural electrical stimulation, mental stress, arousal and deep breaths have been found to cause cutaneous reflex vasodilatation in cold and vasoconstriction in warm subjects. The vasoconstrictions are probably due to increases of sympathetic vasoconstrictor nerve traffic, but whether vasodilatation is due to inhibition of vasoconstrictor nerve traffic or active (= impulse-induced) vasodilatation is unclear. The latter alternative is a possibility since electrical stimulation of the lumbar sympathetic chain may result in skin vasodilatation, suggesting that active vasodilatation is present in the skin of the human foot. Body cooling, which causes a reflex increase of cutaneous sympathetic vasoconstrictor activity, leads to reduction of cutaneous axon reflex vasodilatation. This may be due to competition between vasoconstrictor and vasodilator mechanisms at the blood vessel level. PMID- 2212487 TI - The diagnosis and treatment of autonomic failure. PMID- 2212488 TI - Changes in expression of autonomic nerves in aging and disease. AB - Mechanisms of autonomic neuroeffector transmission are summarised, including evidence for a multiplicity of transmitters, co-transmission, neuromodulation and 'chemical coding' of individual autonomic neurons, where the combination of transmitters they contain is known, as well as their projections and central connections. Changes in expression of autonomic nerves and co-transmitters that occur during development and aging, following trauma, surgery, after chronic exposure to drugs, and in a number of disease situations are described. It is suggested that in neuropathological analysis, compensatory increases in innervation should be considered as well as loss or damage to nerves. Studies of the molecular mechanisms involved in the control of co-transmitter and receptor expression are now needed. PMID- 2212489 TI - Involvement of capsaicin-sensitive nerves of the rat urinary bladder in acrylamide neuropathy. AB - Acrylamide monomer is neurotoxic in man and experimental animals, producing a sensorimotor distal axonopathy. In spite of remarkable effect of acrylamide on micturition, resulting in urine retention in both man and rat, bladder autonomic innervation has been little studied. This study focused on the effect of acrylamide on capsaicin-sensitive nerves of the rat bladder, because of the role played by these fibres in regulating the afferent arm of reflex micturition. PMID- 2212491 TI - Reflex cardiovascular syndromes involving the glossopharyngeal nerve. PMID- 2212490 TI - Investigation on the effect of 30-min tourniquet ischemia on the so-called sympathetic skin response. AB - The effect of ischemia on the sympathetic skin response has been evaluated in a group of healthy volunteers. Sympathetic skin response elicited by an electro tactile stimulation has an afferent A beta fibre pathway and an efferent sympathetic postganglionic C fibre pathway. Even if 30' ischemia was able to block tactile sensory afferent (A beta fibres) the sympathetic skin response was still present, suggesting a concomitant activation of other levels of integration in the genesis of the sympathetic skin response. PMID- 2212492 TI - Spectral analysis of short-term heart rate variability in diabetic patients. AB - Spectral analysis of short term R-R variability estimated by autoregressive modelling is a recently developed method for the evaluation of cardiovascular autonomic function. This new test also allows to study the interaction on heart rate variability of parasympathetic and sympathetic system. The sensitivity of the method for detection of cardiovascular autonomic neuropathy has been evaluated in a group of diabetic patients in comparison with the sensitivity of a battery of the most commonly used cardiovascular autonomic tests (deep-breathing, lying-to-standing, Valsalva Manoeuvre, postural hypotension and hand grip). Spectral analysis of heart rate variability resulted in a very sensitive method for early detection of diabetic autonomic neuropathy, about one-fourth of diabetic patients with normal traditional cardiovascular autonomic tests had abnormal results at spectral analysis. Both sympathetic and vagal control of heart rate resulted alterated in diabetic autonomic neuropathy. PMID- 2212493 TI - Differentiation of cardiac conducting cells from the neural crest. AB - Some of the cells that migrate to the dorsal myocardium of the chick embryo in stage 21 H-H begin to synthesize desmin. They retain this property even when they reach the subendothelial layers of the heart bud, i.e. the characteristic site of the cardiac conducting cells. PMID- 2212494 TI - On the plasticity of form and structure of enteric ganglia. PMID- 2212496 TI - Effects of sympathetic activation on heart rate variability in Chagas' patients. AB - To assess the alterations present in neural control of heart rate in patients with signs of Chagas' disease we studied the spectral components of heart rate variability in 10 Chagas' patients, without cardiac failure, and in 10 control subjects during supine and standing position. Chagas' patients during standing did not present the changes in the spectral components of heart rate variability which normally accompany sympathetic activation and vagal withdrawal. PMID- 2212495 TI - Mechanisms underlying the recovery of urinary bladder function following spinal cord injury. AB - Micturition in cats and rats with an intact neuraxis is dependent upon a spinobulbospinal reflex activated by A delta bladder afferents. This report describes changes in micturition reflexes 2 h to 14 weeks following spinal cord transection at the lower thoracic level. In acute spinal cats micturition reflexes were blocked, however, several weeks after transection, a long latency (180-200 ms) spinal reflex could be activated by C-fiber bladder afferents. This reflex was blocked by capsaicin in doses (20-30 mg/kg, s.c.) that did not affect micturition reflexes in intact cats. Micturition reflexes were unmasked in acute spinal and facilitated in chronic spinal cats by naloxone, an opioid antagonist. Spinal neurons and axons containing opioid peptides were more prominent below the level of transection in chronic spinal cats. VIP, a putative neurotransmitter in C-fiber bladder afferents, inhibited micturition reflexes when injected intrathecally (2-10 micrograms) in intact cats but facilitated micturition reflexes in spinal cats (doses 0.1-1 micrograms, i.t.). VIP-containing C-fiber afferent projections to lamina I of the sacral spinal cord expanded in spinal cats. Thus VIP afferents may have an important role in the recovery of bladder reflexes after spinal injury. Paraplegic animals also exhibit bladder-sphincter dyssynergia, which causes functional outlet obstruction. Studies in rats have revealed that outlet obstruction induced by partial urethral ligation facilitates spinal micturition reflex pathways and causes an expansion of HRP-labelled bladder afferent projections in the spinal cord. These findings raise the possibility that the alterations in central reflex connections in paraplegic animals may be induced in part by changes in peripheral afferent input secondary to outlet obstruction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212497 TI - Pathogenesis of cardiac neuro-myopathy in Chagas' disease and the role of the autonomic nervous system. PMID- 2212498 TI - On the function of spinal primary afferent fibres supplying colon and urinary bladder. AB - The neurophysiological basis of visceral sensations in general and pain in particular have been mainly studied with short-lasting stimuli that simulate the acute events of visceral organ function. Pelvic viscera are supplied by spinal afferents which are involved in the coordinated reflex regulation of continence and evacuation of bowel and bladder and are capable of signalling impending or frank tissue damage. Typically, each afferent neuron innervates one viscus only. The organ-specific subtypes are functionally homogenous and encode by their discharge frequency the information for organ regulation, non-painful and painful sensations. Thus, pain elicited from these organs under physiological conditions is probably not elicited by a specific set of nociceptive visceral afferents. While the use of brief stimuli has yielded invaluable neurophysiological information for normal, healthy viscera, it has fallen somewhat short of providing information about the neuronal basis of chronic visceral pain states. Using pathological models such as experimental inflammation of the urinary bladder and ischaemia of the colon we have shown that the receptor properties of most afferents change dramatically. Of particular interest is the discovery of a novel type of visceral receptor which is not excited by extreme noxious mechanical stimuli applied to the healthy tissue but which is vigorously activated at the onset of an inflammation. This means that the number of functionally active primary afferents is not immutable, but critically depends on the state of the tissue. This new principle of plasticity in the peripheral nervous system bears some considerable importance for the understanding of the genesis of chronic visceral pain states.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212499 TI - Vagal stimulation and exogenous acetylcholine in isolated rat stomach: calcitonin effect on contractile activity. AB - Calcitonin induces contraction in the vascular and extravascular smooth muscle and facilitates the transmission of the excitation in somatic motor nerve endings. These actions are Ca2(+)-dependent. The calcitonin effect on autonomic nerve endings has been studied here by testing influence of calcitonin on the contractile responses of the isolated rat stomach. The organ was submitted to electrical vagal stimulation or, after denervation, to exogenous acetylcholine. Calcitonin invariably increased the muscular tone and reduced the contractile responses to vagal stimulation. Opposite effects were noted after a serotoninergic block with nicergoline. Calcitonin also increased the contractile response evoked by exogenous acetylcholine and the Ca(2)-antagonist nicardipine counteracted the facilitatory effects. We suggest that the inhibitory action of calcitonin is serotonine-dependent while the facilitatory one is Ca2(+) dependent. PMID- 2212500 TI - Spectral analysis of sympathetic discharge in decerebrate cats. AB - To evaluate if the 0.1-Hz low-frequency oscillations of R-R interval are a reflection of rhythmical pattern of discharge of the sympathetic outflow, we analysed in 10 decerebrate cats heart rate and cardiac sympathetic efferent discharge variability. A predominant low-frequency component was present in both signals, thus suggesting that the 0.1-Hz rhythm indeed reflects a rhythmical pattern of discharge of sympathetic outflow. PMID- 2212501 TI - [Non-freeze myopic keratomileusis. Retrospective study of 27 consecutive operations]. AB - 27 consecutive cases of non freeze myopic keratomileusis (using Barraquer Krumeich Swinger Set) were performed by one surgeon on 22 patients in a retrospective study. 4 per operative complications were noticed. Visual acuity with and without correction, astigmatism before and after surgery were reviewed preoperatively, at 1 week, 1 month, 3 months, 6 months and 1 year postoperative. The preoperative myopia (mean +/- standard deviation) was -15.55 +/- 5.46 D, the average postoperative residual myopia was: at 1 week -0.43 +/- 3.58 D, at 1 month -1.18 +/- 4.15 D, at 3 month -4.44 +/- 4.80 D, at 6 month -5.43 +/- 5.51, at 1 year -6.95 +/- 4.81 D. Visual acuity without correction was always better postoperatively. The best visual acuity (with correction) was preoperatively 0.38 +/- -0.22 at 1 week postoperative 0.21 +/- 0.09, at 1 month 0.35 +/- 0.16, at 3 month 0.31 +/- 0.15, at 6 month 0.32 +/- 0.15, at 1 year 0.34 +/- 0.17. Further investigation is monitoring to assess the predictability and stability of non freeze keratomileusis. PMID- 2212502 TI - [Inlay corneo-conjunctival lamellar graft, preliminary step in surgical treatment of the sequelae of corneal burns]. AB - Surgical rehabilitation of the eye following severe burns is difficult and frequently leads to failure. Penetrating keratoplasty gives functional improvement which is often of short duration because of recurrence of the epithelial defect or because of the gravity of the initial injury. A method which includes a first step before corneal transplantation is described: a lamellar corneo-conjunctival autotransplantation, from the uninjured fellow eye is performed in order to improve the epithelial condition of the injured eye prior to later penetrating keratoplasty. This lamellar graft was performed on 25 patients between 1984 and 1988. Analysis of the results demonstrates the efficacy of the method: no complications were noticed on the grafted or the uninjured eye; visual acuity was improved in 76% of cases; the following penetrating keratoplasty led to a good result (clear graft at one year) in 88% of cases; and in 16% of cases, functional improvement gained with this first surgical step was sufficient to avoid having to carry out the penetrating keratoplasty. PMID- 2212504 TI - [Primary open-angle glaucoma. Effects of an eyedrop combining timolol and pilocarpine on the ocular pressure]. AB - In a limited group of open angle glaucoma patients treated twice daily with timoptol 0.5% and having by this treatment a mean intra-ocular pressure of 21-22 mmHg, the association of timoptol 0.5% with pilocarpine 2% respectively, lowered the intra-ocular pressure to an average of 17.8 mmHg and 16.6 mmHg after one and three weeks of continuous treatment. For this study, the patients have been divided into 3 groups: A group treated with timoptol 0.5% alone throughout the 49 days of the study. A group treated with timoptol 0.5%-pilocarpine 2% (timpilo 2) from day 21 to day 49. A final group treated with timoptol 0.5% until day 21 and then with timoptol 0.5%-pilocarpine 4% (timpilo 4) through out day 49. These patients stopped the treatment before the end of the study. Intra-ocular pressures were measured on days 0, 21 and 49. We found a higher drop of pressure (-4.8 mmHg) in the timpilo 2 group than in the timoptol 0.5% group (-1 mmHg) before instillation as well as 2 hours afterwards (-5.25 mmHg and -2 mmHg respectively). The secondary local effects were due to miotics agents. The secondary systemic effects were those inherent to beta-blockers. These results are comparable with a multicentric study of 220 patients, therefore statistically significant. PMID- 2212503 TI - [Degenerative myopia: recurrence of subretinal neovessels after laser photocoagulation]. AB - Macular subretinal neovascularization is one of the most important causes of impaired vision in eyes affected by pathologic myopia. Results of studies concerning the natural history of subretinal neovascularization are inconclusive and contradictory. Like in other macular degenerations, laser photocoagulation could be useful in treating neovascular membranes. Available results indicate that laser treatment can reduce the risk of severe visual loss. However recurrent neovascularization may complicate laser treatment with further visual loss. The authors have reviewed the records of 98 eyes affected by pathologic myopia (axial length a 26.5 mm) and macular subretinal neovascularization that underwent laser photocoagulation. 41 eyes (42%) developed one or more recurrences during a 12 months follow-up period. No relationship was found between sex, age, axial length, distance from the center of the foveal avascular zone or size of neovascular membrane, and recurrence rate. Eyes that experienced recurrences had a final visual acuity significantly worse than the others (p = 0.02). 65% of recurrences was observed in the first 3 months after treatment. 67% of such neovascularizations was located at the foveal side of the laser scar. These data underscore the necessity for close, careful follow-up of all patients who have undergone treatment of a subretinal neovascularization. PMID- 2212506 TI - [Pterygium. Course and treatment]. PMID- 2212505 TI - [Bilateral choroidal osteoma in an aged patient]. AB - The authors report a case of choroidal osteoma in an elderly patient. The affection was bilateral and multifocal. This rare benign tumor mostly affects young females. We report the outcome of the clinical and instrumental examinations leading to the diagnosis of choroidal osteoma. The patient underwent retinal fluoroangiography, A and B-scan ocular ultrasonography, Computerized Axial Tomography (CAT) with and without dye, orbit RNM, and electroretinography. The same investigations were performed 6-7 months after the first control. No changes in the findings were found except for retinal fluoroangiograms that revealed an increased area of the most central lesion in the right eye. Particularly relevant among these diagnostic techniques were ocular ultrasonography and CAT, which revealed the osseous nature of the tumor. Contact B-scan ultrasound examination showed a small number of dense opacities in both eyes. In the retrobulbar area the tumor caused diminution in echo amplitude. A scan examination showed high reflectivity peaks (100%) corresponding to the lesion that were detectable even with reduced sensitivity of the system and, in the orbit, low reflectivity that confirmed the tumor's enhanced ultrasound absorption. CAT detected small calcified areas corresponding to the location of the lesions. Haematochemical examinations performed at each control to measure blood calcium, phosphate and alcaline phosphatase were in the normal range. Urinalysis also excluded possible systemic affections underlying the chorioretinal pathology. We discuss possible pathogenetical hypothesis focusing on the age and sex of the patient. These factors in fact, rule out both the hypothesis of a osteogenesis inhibiting factor present in the last 20-30 years of age and the hypothesis of endocrine stimulation in female patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212507 TI - [Aspiration of silicone oil]. PMID- 2212509 TI - [Transitory eye pain during sleep]. AB - Transitory eye pain occurred during sleep in a 62 year-old patient, who complained of being often awoken during the second half of the night. Diurnal ophthalmologic examinations did not reveal any abnormality. Three consecutive nocturnal polysomnographic recordings were performed to determine whether these pain crises were related to any sleep stage. The patient woke up three times during the recordings because of the usual pain occurrence. On the three occasions, the crisis occurred during of immediately after a REM sleep phase. The brievity of the pain episode (4 to 5 min) did not allow a quick eye pressure measurement to demonstrate a possible increase in ocular tension. However, the role of the REM sleep myosis and vegetative manifestations are discussed regarding the determination of eye pain. PMID- 2212508 TI - [Eye injuries caused by vesicatory insects]. AB - Ocular injuries by vesicatory insects appear exceptional and the authors have not found any reports in the literature. Cantharidine, with toxicity comparable to that of mustard gas, can be present in many species of coleoptera. It results in progressive corneal necrosis ending in ocular perforation in 30 days. The necrotic process persists with long duration because this material is not broken down. It provokes deep ocular injuries (cristalline lens). The inflammatory reaction is severe with acute refractory hypertension. There exists no antidote, only prevention is useful. Emergency penetrating keratoplasty with anterior chamber lavage should help eliminate the toxin. In daily practice, the authors observe similar but less serious injuries; they think that they could be due to dust rich in vesicatory insect debris or their secretions. PMID- 2212510 TI - [A case of tuberculoma of the orbit with sphenoidal origin]. AB - We report the case of an orbital and sphenoidal tuberculosis observed in a young Indian man living in France. The orbital disease is presenting as an orbital mass with a radiologic bony lytic aspect, without systemic manifestation. A malignant process was suspected. The diagnosis was obtained by the culture for Mycobacterium tuberculosis of the biopsy specimen. Orbital involvement in tuberculosis is a rare manifestation in developed countries. Most cases reported in the literature were reported from Asia and Africa. Orbital tuberculosis may become established in one of two ways: primarily by heamatogenous spread to cause a periostitis or a tuberculoma of the orbital tissues, or secondarily by direct extension from neighbouring structures. It occurs in patients with or without associated pulmonary tuberculosis. Mycobacterium tuberculosis should be considered in the differential diagnosis of inflammatory orbital diseases. This diagnosis is based on clinical feature, positive tuberculin skin test and positive culture in resected tissues. The complete resolution of the disease with the specific antituberculous drugs emphasizes the point that tuberculosis must be evocated. PMID- 2212512 TI - [Risk of infection and artificial induction of labor]. PMID- 2212511 TI - [Ocular toxoplasmosis and AIDS. A case report]. AB - Ocular toxoplasmosis is uncommon in the natural course of AIDS. We report here in a case of a 27 year old man with cerebral toxoplasmosis involvement with neurological signs and coma. After an initial improvement with a sulfadiazine and pyrimethamine treatment, we noticed a foveal chorioretinitis with hyalitis in the right eye which deeply decreased the visual acuity (less than 20/400) strongly suggesting a toxoplasmic etiology. Then specific aspects such as serology, acquired or congenital toxoplasmosis, treatment are reviewed. PMID- 2212513 TI - [Risk of infection in fetuses and neonates during delivery with prematurely ruptured membranes at less than 37 weeks]. PMID- 2212515 TI - [Mother-to-fetus contamination during delivery in HIV-positive women]. PMID- 2212514 TI - [Mother-to-fetus contamination in lower genital tract infection caused by common pathogens and Chlamydia]. PMID- 2212516 TI - [Response of gonadotropic hormones and ovarian steroids to various LH-RH agonists. A comparative study]. PMID- 2212518 TI - [Treatment of endometriosis with LH-RH analogs]. PMID- 2212517 TI - [GnRH analogs. Clinical results in IVF]. PMID- 2212519 TI - [Use of LH-RH agonists in uterine leiomyoma]. PMID- 2212520 TI - [Should delivery be medicalized or not?]. PMID- 2212522 TI - Research on religion and mental health in later life: a review and commentary. PMID- 2212521 TI - The influence of general health status on the relationship between chronological age and depressed mood state. PMID- 2212524 TI - Health policy and the disadvantaged. PMID- 2212523 TI - On purpose, successful aging, and the myth of innocence. PMID- 2212525 TI - Health policy and the disadvantaged. Introduction. PMID- 2212526 TI - Child health policy in the U.S.: the paradox of consensus. AB - The U.S. spends more of its total GNP on health services than any other nation, yet it has one of the highest infant mortality rates in the industrialized world. Young American children are immunized at rates that are one-half those of Western Europe, Canada, and Israel. In the mid-1980s, a consensus among policymakers on the need for federal action to improve child health services resulted in the expansion of Medicaid eligibility for pregnant women and young children and the separation of Medicaid eligibility from eligibility for AFDC. The current phase of child health policymaking includes discussion of much broader proposals for changes in health care financing and innovation in health care delivery. This examination of child health policy begins by reviewing the politics of maternal and child health services from the early twentieth century to the Reagan administration, including the role of feminist movements, the development of pediatrics, and the expansion of federal involvement during the 1960s. Next, the politics of Medicaid expansion as a strategy for addressing child health issues are discussed. Current critiques of child health services in the U.S. are examined, along with proposals to restructure health care financing and delivery. Central to the politics of child health policy during the 1980s and into the 1990s is the way in which child health has been defined. Infant mortality and childhood illness are presented as preventable problems. Investment in young children is discussed as a prudent as well as a compassionate policy, one which will reduce future health care costs and enhance our position in the international economy. Unlike other "disadvantaged groups," children are universally viewed as innocent and deserving of societal support. Framing child health issues in these terms helped to produce consensus on the expansion of Medicaid eligibility. Yet the issues beyond the expansion of Medicaid eligibility involve the restructuring of health care financing and delivery, and, on these issues, conflict is far more likely than consensus. PMID- 2212528 TI - Domestic food policy in the United States. AB - In this paper we review the major outlines of domestic food programs, assess their adequacy, and recommend ways to improve the relationship between food programs and hunger relief. In the Food Stamp Program we treat problems of outreach, coverage and the adequacy of benefits, and rationing access through imposition of costs on recipients. For WIC and commodity distribution programs we also discuss problems associated with the fragmentation of authority and dependence on nonprofit distributors. PMID- 2212527 TI - Health care and the homeless: a political parable for our time. AB - The growth in the number of homeless persons is perhaps the most visible indicator of social disintegration in the 1980s, although health and health care are not the central issues of homelessness. This paper, which draws on the author's experience as chairman of the Committee on Health Care for Homeless People of the Institute of Medicine (IOM), describes what is known about the characteristics of homeless persons and the causes of homelessness, and about the health status of homeless persons, which is often not very good (but not significantly worse, it would appear, than that of other low-income persons). The contemporary history of health services targeted to homeless persons begins with the joint initiative of the Robert Wood Johnson Foundation and the Pew Charitable Trusts in 1985, which became the model for federal support through the Stewart B. McKinney Act of 1987. The McKinney Act, like the IOM report, demonstrates how, in contemporary American politics, there can be widespread political consensus not only about a problem but about solutions, while the resulting policy actions are largely symbolic. PMID- 2212529 TI - Chronic disease and disadvantage: the new politics of HIV infection. AB - HIV infection is now perceived as the end stage of a chronic disease that is spreading most rapidly among blacks and Hispanics. The politics of the HIV epidemic in the 1980s were dominated by four interacting factors: fear and fascination; who had the disease and to whom it seemed to be spreading; the endemic problems of United States social policy; and the impact on policy of advances in scientific knowledge. This paper analyzes the political history of each of these factors and describes the dominant policies of the federal government and the states regarding HIV in the areas of surveillance, prevention, research, and financing. Four uncertainties will have a profound influence on the future politics of the HIV epidemic: how the states and the federal government will address the general problems of paying for the care of people with chronic diseases and providing access to care for the uninsured and the underinsured; the number and distribution of the sexual behaviors that transmit infection with HIV and the effectiveness of policies to persuade people to modify these behaviors; precisely who uses addictive drugs and the effectiveness of measures to change their behavior; and the natural history of the virus. PMID- 2212530 TI - Mental health policy for the 1990s: tinkering in the interstices. AB - That public policy has abysmally failed the chronically mentally ill seems beyond genuine dispute. Successive reforms have foundered on the familiar shoals of overblown expectations and insufficient resources. In this paper, we review current policies affecting the chronic and disabled mentally ill, and we consider some approaches to reform. We begin by trying to identify and characterize the chronically mentally ill and their disabilities. Next, we consider the chaotic patchwork of federal and state programs that has come to replace the asylum. We then criticize several competing models of reform that we believe fail to make an empathic connection with the mentally ill. Finally, we urge a strategy of limited reform consistent with available empirical data about program effectiveness and sensitive to the likely economic, political, and legal constraints of the 1990s. PMID- 2212532 TI - The deconstructed center: of policy plagues on political houses. PMID- 2212531 TI - The medically uninsured: problems, policies, and politics. AB - The ranks of the medically uninsured have grown significantly in recent years, but no consensus on a policy solution has emerged. After summarizing the characteristics of the uninsured population, this paper reviews diverse policy responses and their troubled political prospects. PMID- 2212533 TI - The Second Shimoda International Symposium on Gastroduodenal Mucosal Protection. Proceedings of a symposium. Shimoda, Shizuoka, Japan, November 24-25, 1988. PMID- 2212534 TI - Alternation of gastric mucosal glycoprotein (lectin-binding pattern) in gastric mucosa in stress. A light and electron microscopic study. AB - Gastric mucosal cells of the rat glandular stomach were studied by light and electron microscopic procedures by use of lectins in the development of acute gastric mucosal lesions. Effects of the H2-receptor antagonist sofalcone (2'carboxymethoxy-4,4'-bis 3-methyl-2) and truncal vagotomy with pyloroplasty on lectin binding sites and distribution were also investigated. Biotinylated lectins in combination with ABC (avidin-biotinyl peroxidase complex) method were used for light and horseradish peroxidase (HRP)-labeled lectins for electron microscopic studies. Gastric mucosal cells showed the specific binding pattern for each lectin by light microscopy. Especially, binding sites and distribution of peanut agglutinin (PNA) were characteristic after induction of stress, truncal vagotomy, and administration of each drug. Staining and distribution increased in the gastric mucosa upward and downward after that. In electron microscopic studies, PNA strongly stained the membranes of the intracellular secretory canaliculi of a parietal cell. These results suggested that alternation of binding sites and distribution was regulated by change of gastric mucosal blood flow and of acidity in the parietal cells. Therefore, increase of glycoconjugate distribution is supposed to be a possibility of cytoprotective effect for a change of environment in the parietal cells. PMID- 2212535 TI - Generation of ammonia and mucosal lesion formation following hydrolysis of urea by urease in the rat stomach. AB - We examined the morphological changes in gastric mucosa and the generation of ammonia after exposure of the rat stomach to urea in the presence of urease, in attempts to investigate a pathophysiological role of urea, urease, and ammonia system in gastric ulcer diseases. Exposure of the stomach for 20 min to 2 ml urea (0.025-0.2%) together with urease (100 IU) induced histological damages in a concentration-related manner. Either urea or urease alone did not induce any histological change in the mucosa. Instillation of urea into the stomach generated ammonia in the presence of urease; the amount of ammonia was increased depending on the concentration of urea, and was closely associated with the severity of histological damage. The exposure of the stomach to ammonia (NH4OH: 0.01-0.1%) also produced histological damages in the gastric mucosa in a concentration-related manner. The characteristics of injury induced by 0.5-1.0% ammonia were stasis of microcirculation, disruption of the surface epithelial cells, and necrosis of the mucosa. These results demonstrated that ammonia generated from the hydrolysis of urea by urease in the stomach causes damages in the gastric mucosa. PMID- 2212537 TI - Effect of gastric mucus on the uptake of the carcinogen MNNG by gastric mucosal DNA. AB - In prostaglandin E2 (PGE2)-, pirenzepine-, and indomethacin-administered rats, the incorporation of N-[methyl-3H]-N'-nitro-N-nitrosoguanidine ([methyl-3H]MNNG) into gastric mucosal DNA was measured quantitatively by liquid scintillation counting after intragastric instillation of [methyl-3H]MNNG. The amount of incorporation was 25.4 +/- 5.9 pmol/mg DNA in control rats, 11.7 +/- 3.8 pmol/mg DNA in PGE2-administered rats, 6.2 +/- 5.6 pmol/mg DNA in pirenzepine administered rats, and 42.9 +/- 14.4 pmol/mg DNA in indomethacin-administered rats. PGE2 and pirenzepine significantly decreased the incorporation as compared with the control group. In contrast, indomethacin increased the incorporation. In addition, gastric mucosa of these drug-treated rats was studied histochemically. PGE2 and pirenzepine increased secretion of gastric mucus whereas indomethacin decreased it. It is possible that gastric mucus has a protective effect not only against ulcerogenic agents but also against carcinogens. It is considered that gastric mucus plays an important role in the defense mechanism against carcinogenesis. PMID- 2212536 TI - The Na+/H+ exchange and H+ diffusion properties of human postmortem mucus: a comparison of gastric antral, gastric body, jejunal and ileal mucus. AB - The stomach and small intestine are areas of major electrolyte and solute transport. Mechanisms of transport in these areas have been widely studied and basic understanding is available. However, the mucus that lines the stomach and intestine is an important layer whose properties and functions in electrolyte and solute transport are not well understood. In this study we examined the Na+/H+ exchange of mucus from the stomach body and antrum, the jejunum, and the ileum. Mucus from the stomach body and antrum is a cation exchanger, a property that aids the net unidirectional flux of H+ ions from parietal cells to lumen. In the jejunum and ileum, mucus is an anion exchanger, which may be important in solute transport and absorption in the small bowel. In both the stomach and small bowel, proton movement is slow, which helps maintain the uphill pH gradient across gastric mucus and the downhill pH gradient across small intestinal mucus. PMID- 2212539 TI - The susceptibility of Campylobacter pylori to antiulcer agents and antibiotics. AB - The antibacterial activities of antiulcer agents and antibiotics against Campylobacter pylori were studied. The MIC90 values of three kinds of antibiotics -macrolides, beta-lactams, and metronidazole--were 0.05-0.78, 0.39-1.56, and 12.5 micrograms/ml, respectively. They were more active than antiulcer agents such as H2-blockers and cetraxate with MIC90 values of greater than or equal to 1,600 and greater than 1,600 micrograms/ml, respectively. Especially, clarithromycin, a new derivative of erythromycin, showed an MIC90 of 0.05 microgram/ml. However, the other antiulcer agents such as sofalcone and tripotassium dicitrate bismuthate (TDB) also had MIC90 values of 50 and 6.25 micrograms/ml, respectively. Clarithromycin, sofalcone, and TDB showed bactericidal activity against C. pylori CLO2. The bactericidal actions of these drugs could be observed under electron microscopy. PMID- 2212538 TI - Correlation of gastric mucous volume with levels of five prostaglandins after gastric mucosal injuries by NSAIDs. AB - After administration of NSAIDs (aspirin and indomethacin), chronological changes in gastric mucous volume were determined. These mucous volume changes were evaluated in relation to the development of gastric mucosal injuries. Furthermore, quantitative changes in five kinds of prostaglandins (PGs) in the gastric mucosa were measured after administration of NSAIDs. Gastric mucus volume was measured using a video image processor (VIP), and five kinds of PGs were fractionated by high-performance liquid chromatography (HPLC) and quantitatively determined by radioimmunoassay (RIA). We found that NSAIDs decrease the levels of five kinds of PGs to the same extent. Also, gastric mucous volume is decreased after administration of aspirin and increased after administration of indomethacin. Accordingly, it is possible that each NSAID has a different mechanism of producing the gastric mucosal injury and acts on gastric mucus in a different manner. There was no parallel in changes between gastric mucous volume and PG levels of the different PGs in the gastric mucosa after administration of NSAIDs. PMID- 2212540 TI - "Healed" experimental gastric ulcers remain histologically and ultrastructurally abnormal. AB - The present study was designed to assess histologic and ultrastructural features of gastric mucosa in the areas of grossly healed ulcers (acetic acid-induced gastric ulcers) in rats. The specific question we studied was whether the structure and cellular composition of the gastric mucosa in an area of grossly healed ulcer were fully restored. Eighty Sprague-Dawley rats underwent laparotomy; 100% acetic acid was applied to the lower gastric corpus serosa for 30 s and the abdomen was closed. The stomachs were reopened after 2 weeks or after 2, 3, or 4 months. Standardized gastric wall specimens from the area of grossly healed ulcers were obtained, processed, and evaluated by light microscopy and by transmission electron microscopy. The gastric mucosa of grossly healed ulcers demonstrated re-epithelialization at each study time but the mucosa beneath the surface epithelium displayed prominent histologic and ultrastructural abnormalities. Two different patterns of scar could be distinguished: (a) the mucosa in the area of healed ulcer was thinner (25-45% reduction vs. normal), with increased connective tissue and poor differentiation and/or degenerative changes in the glandular cells; or (b) the mucosa displayed ballooning dilatation of gastric glands, reduction in the microvascular network, and poor differentiation of glandular cells. We conclude that (i) the subepithelial mucosa of grossly healed gastric ulcer displays disorganized restoration of glandular and vascular structures and remains histologically and ultrastructurally abnormal; (ii) these abnormalities may interfere with oxygenation, nutrient supply, and with mucosal resistance and defense, and therefore could be the basis for ulcer recurrence. PMID- 2212541 TI - Vascular and microvascular changes--key factors in the development of acetic acid induced gastric ulcers in rats. AB - The present study examined the time sequence and histologic and ultrastructural features of the formation and evolution of experimental, acetic acid-induced gastric ulcerations in rats. One hundred percent acetic acid was applied to the gastric serosa of 140 fasted male Sprague-Dawley rats through a polyethylene tube for 30 s. Gastric mucosal changes were evaluated at 1, 5, 15, and 30 min, 1 and 3 h, and 1, 2, 3, 5, 8, and 11 days after acetic acid application by visual inspection, by quantitative and qualitative light microscopy, and by transmission electron microscopy. Following exposure to acetic acid, the earliest morphologic changes occurred at 1 min and consisted of dilatation of large submucosal veins and arteries and mucosal collecting venules. Five to 15 minutes after injury, thrombi developed in submucosal veins and collecting venules, leading to microvascular stasis and mucosal necrosis. By 3 h, necrotic masses started to detach. By 24-48 h, necrotic changes penetrated the submucosa. By 72 h, most ulcers underwent transition into a "chronic" stage characterized histologically by the presence of granulation tissue at the bottom, and the appearance of a transitional healing zone at the margins. By 5 days, an increased amount of granulation tissue was observed and the gastric glands in transitional zones at the ulcer margin displayed cystic dilatation. Based on this study, we conclude that a key feature of acetic acid-induced ulcer formation is the early vascular and microvascular injury, which precedes glandular cell necrosis. PMID- 2212542 TI - Protective effect of PGD2 against ethanol-induced gastric mucosal injury in rats. AB - The protective effect of prostaglandin D2 (PGD2) in ethanol-, HCl-, or NaCl induced gastric mucosal injury was investigated. To clarify the mechanism, the gastric mucosal hemodynamics were also investigated using reflectance spectrophotometry and laser Doppler flowmetry in anesthetized rats. PGD2 administered orally significantly reduced the ethanol-induced mucosal injury. Although it did not reach any significance, PGD2 also reduced 0.6 N HCl-induced mucosal damage, and slightly reduced 25% NaCl-induced mucosal damage. Topical application of PGD2 did not affect gastric mucosal hemodynamics at steady state before the administration of necrotizing agent. However, PGD2 significantly improved the gastric mucosal microcirculatory congestion caused by ethanol, and partly improved 0.6 N HCl-induced ischemia. However, it did not improve the 25% NaCl-induced mucosal congestion. The results indicated that PGD2 had a protective effect in the ethanol-induced gastric mucosal injury through the improvement of gastric mucosal microcirculation. However, further investigations are needed to clarify the precise effect of PGD2 in 0.6 N HCl- or 25% NaCl-induced mucosal damage. PMID- 2212543 TI - Protective effect of sofalcone and 16,16-dimethyl-PGE2 on isolated rat gastric cells. AB - The effects of 16,16-dimethylprostaglandin E2 (dm-PGE2) and sofalcone on damage caused by ethanol in surface epithelial cells isolated from rat stomach were examined. The surface epithelial cells (SECs) accounted for 83% of the isolated gastric mucosal cells, mucus neck cells for 5%, parietal cells for 9%, and chief cells for 3%. To suspensions of SEC, either dm-PGE2 at concentrations of 10(-7), 10(-6), or 10(-5) M or sofalcone at concentrations from 5 X 10(-6) to 10(-4) M was added; some cells were treated with neither drug. Ten minutes later, ethanol was added to each cell suspension to a final concentration of 15%, and 5 min later the viability was evaluated by trypan blue exclusion. At 10(-6) M, dm-PGE2 reduced ethanol-induced cell damage most strongly (p less than 0.001). Sofalcone also helped to prevent cell damage caused by ethanol in a dose-dependent manner. These results suggest that dm-PGE2 and sofalcone protect gastric mucosa not only from gross visible damage but they directly protect gastric cells from damage. PMID- 2212544 TI - Further study of mucosal repair by sofalcone in experimental gastritis. AB - The effect of sofalcone on the glandular structure and cell proliferation in the gastric mucosa of rats with gastritis induced by the administration of sodium taurocholate (TCA) for 6 months was examined by histoquantitative analysis and [3H]thymidine autoradiography. Morphometric observation revealed that, with TCA treatment, mucosal thickness, parietal cell mass, and the ratios of the length of the glandular portion/total length of the gastric gland were decreased in both the fundic and pyloric glands. Inflammatory cell infiltration and collagenous fiber proliferation were present in the gastric mucosa following TCA and indicated the presence of atrophic gastritis. These atrophic changes and inflammatory cell infiltration were reversed by a 3 week administration of sofalcone. Cellular proliferative activity assessed by the labeling indices of the gastric mucosa increased in TCA-induced gastritis in rats. The administration of sofalcone to rats with TCA-induced gastritis significantly increased labeling indices, particularly in the pyloric glands. From these results, it appears that sofalcone stimulates the compensatory increase in proliferative activity of generative cells, which then may become available to heal the gastritis. PMID- 2212545 TI - Effect of epidermal growth factor in combination with sucralfate or omeprazole on the healing of chronic gastric ulcers in the rat. AB - Epidermal growth factor (EGF) has been shown to enhance healing of experimental gastric ulcers when given subcutaneously or orally in the drinking water. This effect of EGF occurs without reducing gastric acid secretion. On the other hand, EGF reportedly is excreted rapidly from gastric lumen when administered by intragastric bolus. This suggests that further stimulation of ulcer healing may be expected if EGF is given with an acid-suppressive agent or with an agent allowing EGF to remain in rat gastric lumen at high concentrations. In the present study, EGF administered by gastric intubation at a dose of 10 micrograms/kg, which is three times smaller than reported in previous studies, was evaluated for its effect on acetic acid-induced rat gastric ulcers in combination with sucralfate or omeprazole. Sucralfate is well known selectively to bind proteins covering the ulcer base, and omeprazole is a potent acid suppressive agent. Prior to the study of combined EGF and sucralfate, oral sucralfate was confirmed to allow endogenous gastric EGF and mouse EGF given exogenously to remain at high concentrations in gastric contents and tissues. EGF and sucralfate (2 g/kg/day) given alone failed to stimulate ulcer healing in submandibularectomized rats (SMR rat) whose endogenous gastric EGF was depleted. However, the combination of both drugs administered at the same doses significantly accelerated ulcer healing in the SMR rat. Omeprazole (200 mg/kg/day) significantly enhanced ulcer healing regardless of removal of the submandibular glands. The combination of EGF and omeprazole further stimulated ulcer healing in the SMR rat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212546 TI - Effects of cigarette smoke and nicotine on duodenal bicarbonate secretion in the rabbit and the rat. AB - The effects of short-time exposure to cigarette smoke on duodenal mucosal bicarbonate secretion were studied in anesthetized rabbits and rats. The bicarbonate secretion was measured by continuous titration of recirculating luminal perfusate. In artificially ventilated rabbits, intermittent exposure to cigarette smoke during two 10-min periods caused a marked (approximately 40%) decrease (p less than 0.01) in duodenal bicarbonate secretion. After the exposures, secretion gradually recovered and had returned to the pre-exposure rate after 50 min. The decrease in secretion was associated with decreases in heart rate (approximately 15%) and blood pressure (approximately 30%) that, however, were of shorter duration. Neither reduced amounts of smoke (1/6 or 1/3) nor nicotine (25-1,000 micrograms/kg, intravenously) had any major effect on the bicarbonate secretion. In the spontaneously breathing rat, smoke was administered for 1-2 breaths every 30 s during a 5-min period. This exposure resulted in a significant (p less than 0.05) decrease in bicarbonate secretion and some increase in the blood pressure. Exposure to smoke had no effect on the secretion in rats with both splanchnic nerves cut, suggesting neural sympathetic mediation of the smoke-induced inhibition. PMID- 2212547 TI - Possible role of endogenous prostaglandins against ethanol injury in rat stomach. AB - Exposure of the gastric mucosa for 3 min to 30% intragastric ethanol induced mucosal injury that appeared dark red in anesthetized rats. Microscopic observation of the microvasculature in the injured area after exsanguination of rats and in living rats confirmed that there was congestion of the blood flow in the collecting venules and capillaries. Hemorrhage was observed about 30 min after application of ethanol. Monastral blue dye was deposited along the postcapillary venules only at the border of the congestion area. A selective 5 lipoxygenase inhibitor, AA-861, inhibited the gastric lesion, and immunoreactive leukotriene C4 (LTC4) was detected in the gastric wall. Previous exposure of the gastric mucosa to 1.0 M NaCl solution inhibited the ethanol-induced mucosal injury markedly. NaCl solutions (0.5-1.0 M) also suppressed the electrical activity of smooth muscle and the suppression was released by indomethacin. Having observed that PGE2 generation in the stomach was induced dose-dependently by intragastric NaCl solutions (0.5-1.0 M), we propose the hypothesis that peptide LTs released by intragastric ethanol constrict the collecting venules or lamina muscularis mucosae and induce congestion of these venules, whereas the PGE2 released by intragastric NaCl solution releases the congestion of the collecting venules directly or through suppression of contraction of the lamina muscularis. PMID- 2212548 TI - In vitro adaptive cytoprotection in gastric cells isolated from rat stomach. AB - The effects of mild irritants (2-5% ethanol or water at 45-55 degrees C) on production of prostaglandins (PGs) in gastric cells isolated from rat stomach and the damage caused by 15% ethanol were assessed. Gastric cells were isolated by the method of Matuoka et al., by which a suspension rich in surface epithelial cells was obtained. Synthesis of PGE2 by the cells was stimulated by 3% ethanol or water at 50 degrees C. The damage caused by 15% ethanol was much less in the cells treated with 3% ethanol or 50 degrees C water beforehand than in untreated cells. This protective effect by 3% ethanol or 50 degrees C water was abolished when the cells were treated with 10(-4) M indomethacin. These results suggest that 3% ethanol or 50 degrees C water protects the gastric cells from damage caused by 15% ethanol, possibly via endogenous PGs. PMID- 2212550 TI - Glycosphingolipid composition of the gastric mucosa. A role of sulfatides in gastrointestinal mucosal defense? AB - The glycosphingolipid (GSL) compositions of the human, rabbit, and rat gastric mucosa were studied and compared. In neutral GSLs, although GalCer was the most abundant component in every tissue examined, species-specific differences were clearly observed in their composition. Acidic GSLs were composed of sulfatides and gangliosides. Every gastric mucosa contained sulfatides (GalCer-sulfate) in a high concentration. The concentrations of sulfatides per gram of dry weight were 416.0, 933.8, 394.0, 365.9, and 135.9 nmol for the human fundus, human antrum, rabbit fundus, rabbit antrum, and rat glandular stomach, respectively. On the other hand, gangliosides were less in these tissues. The molar ratios of sulfatides to GM3, a major ganglioside, were 4.3, 6.7, 11.1, 2.1, and 1.2 for each gastric mucosa described above, respectively. A high sulfatide concentration in animal gastric mucosa, with its structural similarity to sucralfate, implies that sulfatides may play an important role for gastrointestinal mucosal protection. PMID- 2212549 TI - Effects of stress on gastric mucosal prostaglandin generation in intact, adrenalectomized, and sham-operated rats. AB - To study the effects of (a) cold restraint stress and (b) adrenalectomy in association with cold restraint stress on gastric mucosal ulceration and prostaglandin generation, we performed two experiments. In the first, 40 rats were divided into four groups of 10 rats each: (a) unstressed and (b) stressed for 0.5 h, (c) stressed for 2 h, and (d) stressed for 4 h. In the second experiment, another 80 rats were divided into four groups of 20 rats each: (a) adrenalectomy plus cold restraint stress for 2 h, (b) adrenalectomy plus no stress, (c) sham operated plus 2 h of stress, and (d) sham operated plus no stress. In both experiments we recorded an ulcer index and measured mucosal generation of prostaglandin E2 (PGE2) and prostaglandin I2 (6-keto-PGF1a). IN CONCLUSION: (a) Cold restraint stress is associated with a time-dependent decrease in gastric mucosal PGE2 generation, but no change in 6-keto-PGF1a generation, and an increase in mucosal injury that is maximal by 2 h. (b) Adrenalectomy augments the effects of stress on mucosal injury but has no effect on prostaglandin generation; thus, the ulcerogenic effect of adrenalectomy appears to be independent of an effect on prostaglandin generation. PMID- 2212551 TI - Role of oxygen-derived free radicals in the pathogenesis of gastric mucosal lesions in rats. AB - The role of oxygen-derived free radicals and lipid peroxidation in the pathogenesis of acute gastric mucosal erosion was investigated in rat models produced by burn shock stress, by treatment with regional hyperthermia, platelet activating factor, and compound 48/80, and by ischemia-reperfusion. In all experimental models, the increase in the gastric erosions and in TBA reactants in the gastric mucosa were significantly inhibited by the treatment with superoxide dismutase (SOD) and/or catalase. Pretreatment with allopurinol, a competitive inhibitor of xanthine oxidase, prevented considerably the gastric injury (a) induced by burn shock, (b) produced by treatment with compound 48/80, and (c) caused by ischemia-reperfusion. By the treatment with anti-rat neutrophil antibody, the gastric mucosal injuries induced by regional hyperthermia, platelet activating factor, and compound 48/80 were significantly inhibited; however, burn shock and ischemia-reperfusion injuries were not inhibited. These results suggest that oxygen-free radical and lipid peroxidation contribute to the formation of gastric mucosal lesions, and that the sources of oxygen radicals seem to be different among these experimental models. PMID- 2212552 TI - Effects of single parenteral indomethacin injection in rat fundic and antral epithelial proliferation. AB - To study the effects of a single parenteral dose of indomethacin on gastric epithelial proliferation, we performed the following study. Male Wistar rats weighing about 200 g were divided into two groups and given single intraperitoneal injections of indomethacin 5 mg/kg, either suspended in 0.5% carboxymethyl cellulose sodium salt or vehicle alone, after an overnight fast. After 6 h, all rats were injected by tail vein with tritiated thymidine, 1 microCi/g body weight, to label proliferating cells and were killed 1 h later. Sections from fundic and antral mucosae were processed for light autoradiography. Parenteral indomethacin resulted in spotty erosions in fundic mucosa. Histologically, there was congestion with or without epithelial disruption. These areas were excluded in the proliferation measurements. There was a significant decrease not only in the number of labeled cells but also in the thickness of the proliferative zone with the thinning of the entire mucosal thickness in the fundic mucosa. None of the measurements in antral mucosa showed significant difference. These results showed that a single parenteral injection of indomethacin inhibits epithelial proliferation and decreases mucosal thickness in fundic, but not antral mucosa of the rat. PMID- 2212553 TI - Increased microvascular permeability and lesion formation during gastric hypermotility caused by indomethacin and 2-deoxy-D-glucose in the rat. AB - The relationship between lesion formation, gastric motility, and vascular permeability was examined in rats using indomethacin and 2-deoxy-D-glucose (2DG). Both indomethacin (25 mg/kg s.c.) and 2DG (100 mg/kg/h i.v.) produced gastric hypermotility and induced lesions, mostly confined to the rugal crests of the mucosal folds; the onset of hypermotility preceded appearance of the lesions in both cases. The mucosal microvascular permeability as determined by the amount of extravasated dye (Evans blue) was increased in response to these two agents, and the permeability responses also preceded appearance of the lesions. Both the increased vascular permeability and the severity of lesions were significantly reduced when the hypermotility was inhibited by pretreatment with atropine (3 mg/kg s.c.). The severity of the lesions were also markedly reduced or worsened, respectively, by hydrocortisone (10 mg/kg s.c.) or N-ethylmaleimide (10 mg/kg s.c.) at the doses that significantly decreased or enhanced the vascular permeability responses caused by indomethacin and 2DG. These results suggest that the enhanced gastric motility as induced by indomethacin and 2DG may cause microcirculatory disturbances in the specific sites of the mucosa (mucosal folds), probably by abnormal compression of the gastric wall, leading to the increased microvascular permeability and cellular damage. PMID- 2212554 TI - Fibronectin-related substance located in the chief cells of human and rat gastric mucosa. AB - A novel substance located in the chief cells of human and rat gastric mucosa, which was detected immunologically by either polyclonal or monoclonal antihuman fibronectin (FN) antibodies, is reported. All three polyclonal antihuman FN antibodies used in this study reacted immunohistologically exclusively with the chief cells. Monoclonal antibody against C-terminal peptide or cell binding peptide reacted clearly with the human chief cells, but monoclonal antibodies against FN N-terminal and midmolecule failed to react with the cells. Western blot analysis of the rat gastric mucosal extract with polyclonal antihuman FN antibody showed that this substance has a molecular weight of about 70,000 Da. Therefore, this substance appears to be a fragment containing the C-terminal peptide of whole molecule FN and thus in the present study is named FN-related substance (FNRS). In a further study with ethanol-induced ulcer model of the rat, the physiological significance of FNRS was examined. The FNRS decreased remarkably, in a dose-dependent manner, in the fundic mucosa of the rats that ingested ethanol. The FNRS appeared to be associated with development of mucosal damage and repair, subsequently playing, in part, an important role in the gastric mucosal protection mechanism. PMID- 2212555 TI - Mucosal blood flow stasis and hypoxemia as the pathogenesis of acute gastric mucosal injury: role of endogenous leukotrienes and prostaglandins. AB - To clarify the roles of endogenous leukotrienes and prostaglandins in the ethanol induced gastric mucosal injury, the effect of AA-861 (a selective 5-lipoxygenase inhibitor) and indomethacin (a cyclooxygenase inhibitor) on the ethanol-induced gastric mucosal lesions was investigated in fasted rats. Furthermore, the effect of these agents on the gastric mucosal microcirculatory disturbance induced by ethanol was also investigated using laser Doppler velocimetry and reflectance spectrophotometry. Forty percent ethanol caused mucosal microcirculatory stasis and mucosal hypoxemia, followed by mucosal injury. The pretreatment with AA-861 reduced the mucosal injury and significantly reduced the mucosal congestion and hypoxia induced by 40% ethanol. The pretreatment with indomethacin did not reduce the gastric mucosal damage or influence the mucosal blood flow stasis and the mucosal hypoxemia induced by ethanol. These results suggested that the increase of endogenous leukotrienes after intragastric administration of ethanol is responsible for the mucosal microcirculatory disturbance and mucosal tissue hypoxemia resulting in the mucosal injury, and that the decrease of prostaglandins alone may not play an important role in ethanol-induced mucosal injury. PMID- 2212556 TI - Evidence for gastric mucosal cell invasion by C. pylori: an ultrastructural study. AB - It is now generally accepted that Campylobacter pylori is closely associated with peptic ulcer disease and chronic type B gastritis. Whether C. pylori is the direct etiologic cause of either or both of these illnesses remains unclear. Possible pathophysiologic effects of C. pylori are still a matter of debate and conjecture. Utilizing a small group of patients with gastric ulcers and chronic gastritis, we examined the ultrastructural relationship between C. pylori and gastric cells. Forty-eight percent of our gastric ulcer patients and 57% of our chronic gastritis patients had C. pylori in their lower corpus mucosa. Examination with the transmission electron microscope indicated a very close proximation by C. pylori to the surface epithelial cells strongly suggesting adherence. We also describe for the first time the invasion of gastric cells by C. pylori. Although an uncommon occurrence, we had repeated observations of C. pylori invading surface epithelial cells, parietal cells, and chief cells. Most of the intracellular C. pylori were intact but other forms appearing to be degenerating organisms were also seen. We suggest that cell invasion may be one mechanism by which C. pylori causes pathologic changes in the gastric mucosa. These observations may also explain why C. pylori chronically infects gastric cells and frequently recurs after treatment. PMID- 2212557 TI - Campylobacter pylori interactions with gastric cell tissue culture. AB - Many investigators have reported that gastric mucosal biopsies of patients with chronic gastritis and peptic ulcer disease show the presence of Campylobacter pylori in a large majority of cases. Histologic examinations of such tissues indicate a close approximation of C. pylori with gastric surface epithelial cells. A recent report has described both adherence and cell invasion of gastric cells by C. pylori. Using a transmission electron microscope, we have examined the interaction between C. pylori, C. jejuni, and E. coli in vitro with a gastric cancer cell line, Kato III. Our results indicate marked toxicity of E. coli and moderate toxicity of C. jejuni for Kato III cells. C. pylori had only a minor effect on tissue culture viability. C. pylori was found to have a strong association with the Kato III cell membranes and evidence of occasional cell invasion. Both C. jejuni and E. coli showed no attachment or association with the Kato III cells. We interpret these findings as indicating that C. pylori may have a specific adhesion for gastric cells. PMID- 2212558 TI - Neuropsychological outcome of survivors of out-of-hospital cardiac arrest. AB - Thirty patients resuscitated from out-of-hospital cardiac arrest (15 with and 15 without postanoxic coma on admission) underwent a clinical examination and neuropsychological testing. In order to assess quality of life, they were compared to two matched control groups; 15 patients with previous myocardial infarction and 15 healthy subjects. None of the survivors showed severe neurologic impairment, and all had returned to self-sufficient physical activity. However, the behavior rating scale scores were significantly worse in patients with postanoxic coma. The processing ability linked to memory was significantly worse in the postanoxic coma group. Mood disorders were also observed in this group, but they did not have pathological significance. The remarkably low incidence of neurologic and psychological sequelae in these resuscitated patients, particularly in those with early clinical evidence of severe cerebral damage, is an encouraging result that supports the therapeutic systems development and efforts in the management of out-of-hospital cardiac arrest. PMID- 2212559 TI - Scroto-abdominal impalement injury in a skateboard rider. AB - The injuries sustained by skateboard riders vary from minor cuts and abrasions to fractures. This report describes a unique injury sustained by a young skateboard rider who was impaled on a metal rod. Literature review of over 1,254 skateboard injuries did not reveal any other instances of penetrating abdominal trauma. PMID- 2212560 TI - Traumatic rupture of the thoracic aorta presenting as transient paraplegia. AB - A patient involved in a high-speed motor vehicle accident presented paraplegic to the emergency department. He was noted to have an abnormal chest x-ray and, subsequently, underwent aortography which revealed aortic transection. The patient's paraplegia resolved spontaneously prior to definitive aortic repair hours later. Aortic rupture presenting as paraplegia is a rare association, but one an emergency physician should be cognizant of, especially in the case of blunt or decelerating trauma. PMID- 2212561 TI - Pneumatic firearm injuries: trivial trauma or perilous pitfalls? AB - This report describes an injury due to a pneumatic firearm. Though powder firearm injuries are generally considered serious, pneumatic weapon injuries are often viewed as minor or insignificant trauma. Children and adolescents primarily wield these weapons contributing to their "harmless" aura. However, dramatic increases in muzzle and impact velocities have transformed the newer generation of pneumatic firearms into formidable weapons. Consequently, the literature is replete with increasing incidences of serious injury due to pneumatic weapons. PMID- 2212562 TI - A case of unexpected pasteurella multocida bacteremia. AB - A case of Pasteurella multocida bacteremia in a previously healthy hospital employee is presented. The patient had sustained a scratch from his dog four days prior to being seen in the emergency department with adequate healing and no evidence of localized infection. He presented with an acute febrile illness, and was discharged from the emergency department with a diagnosis of viral syndrome. He was asked to return to the hospital the next day when a bacteriology report of gram negative rods in both aerobic and anaerobic blood culture bottles was received in the emergency department. Pasteurella multocida bacteremia/septicemia is seen most frequently in immunocompromised patients but the diagnosis should be considered in any patient with a febrile illness and exposure to cats or dogs. PMID- 2212563 TI - Pelvic pain: lessons from anatomy and physiology. AB - Pelvic pain is often a difficult differential diagnosis in the emergency department. For physiologic reasons, pain in the pelvis is difficult to localize to a specific organ, and pelvic peritonitis is hard to recognize. On the other hand, differences in types of pain can be very useful in arriving at a correct diagnosis. The clinician must learn to recognize superficial and deep somatic pain, and differentiate between various types of visceral pain which originate from inflammation, ischemia, or colic. A review of the anatomy and physiology of pelvic pain helps identify some of the problems as well as potential aids in approaching the patient with pelvic pain. PMID- 2212564 TI - Treatment of phenobarbital poisoning with multiple dose activated charcoal in an infant. AB - A 28-day-old infant developed lethargy, hypotonia, and hypothermia following a phenobarbital overdose secondary to a pharmacist's error. He was treated with multiple dose activated charcoal (MDAC) and alkalinization of the urine, which resulted in prompt recovery with rapid elimination of the drug (t1/2-11.2 hours, expected 45 to 118 hours). The use of MDAC in this newborn was safe and effective. We suggest that age should not pose a barrier to the use of MDAC, when indicated. PMID- 2212565 TI - Tricyclic antidepressant overdose: conservative management in a community hospital with cost-saving implications. AB - Reports of late-onset cardiovascular complications following tricyclic antidepressant (TCA) overdose have led to a very conservative approach to these patients. Many patients have been hospitalized for continuous cardiac monitoring, regardless of the clinical presentation. Management algorithms based on clinical predictors of outcome have recently been proposed. We used the algorithm developed by Tokarski and Young to retrospectively evaluate the care of 33 TCA overdose patients admitted to our hospital over a 3-year period. We then identified 11 patients who could have been treated on an outpatient basis had the algorithm been employed. Ten were admitted to a monitored unit and spent a mean of 31.6 +/- 15.64 hours on the unit. None of the 11 patients developed complications during their hospital stay. Use of the algorithm would have resulted in an estimated cost savings of 13 hospital days and $14,000. PMID- 2212566 TI - Effects of 4-methylpyrazole, methanol/ethylene glycol antidote, in healthy humans. AB - 4-Methylpyrazole (4-MP), an inhibitor of alcohol dehydrogenase, may be useful for the treatment of methanol and ethylene glycol intoxications. A placebo controlled, double blind, multiple dose, sequential, ascending-dose study has been performed to determine the tolerance of 4-MP in healthy volunteers. Oral loading doses of 4-MP were followed by supplemental doses every 12 h through 5 days, producing plasma levels in the therapeutic range. A slight, transient elevation in one or both serum transaminase values was observed in 6 of the 15 subjects treated with 4-MP. This effect was not dose related nor apparently mediated through a hypersensitivity reaction. Serum triglyceride levels were increased in 30% of 4-MP treated subjects, but also in 25% of the placebo subjects. 4-MP treatment did not produce any other significant changes in objective clinical parameters nor in subjective side effects. The results suggest that a mild, transient increase in liver function tests might be observed in some subjects treated with multiple doses of 4-MP. Nevertheless, the slower elimination rate and lesser degree of toxicity of 4-MP would make it preferable to ethanol in therapy of these poisonings. PMID- 2212567 TI - Posttachycardia T-wave changes. AB - A 25-year-old previously healthy man presented to the emergency department with a tachydysrhythmia. After pharmacological intervention, the patient's rhythm converted to normal sinus and symmetrically inverted T-wave changes were noted. Although asymptomatic after conversion, the patient was admitted to the hospital and monitored for two days to rule out cardiac ischemia correlating with the T wave changes. The patient was ultimately discharged in good health. A review of the emergency medical literature fails to reveal examples of post-tachycardic T wave changes that may simulate myocardial ischemia but be of no clinical significance. PMID- 2212568 TI - The normal mediastinum in blunt traumatic rupture of the thoracic aorta and brachiocephalic arteries. AB - In a review of 52 articles, published between 1953 and 1989, 656 patients with blunt traumatic rupture of the thoracic aorta or brachiocephalic arteries were identified. Of these, 608 (92.7%) had an abnormal mediastinum on initial chest radiographs obtained in the emergency department, thus allowing early detection of the vascular injury. Unfortunately, 48 (7.3%) of these patients had a normal mediastinum on their initial chest radiographs. This appears to occur when the traumatic pseudoaneurysm is not accompanied by associated mediastinal hemorrhage or hematoma formation, and the pseudoaneurysm is either small or is situated in such a way that it does not alter the mediastinal contour. The use of accessory clinical and radiographic signs to indicate the need for aortography has been shown to be of very low yield, but would have allowed the early detection of an additional 5.6% of the reported cases. Performing aortography solely on the basis of a history of major decelerating blunt trauma to the thorax remains the only way, in the acute emergency department setting, to detect the 1.7% of patients with aortic or brachiocephalic arterial rupture who have no mediastinal abnormality or accessory clinical or radiographic signs of vascular injury. There is evidence from the literature, however, to suggest that the evaluation of serial chest radiographs obtained at close intervals for the first month following trauma for the development of mediastinal abnormality or large hemothorax is an acceptable alternative to the routine performance of aortography in those blunt chest trauma victims with no clinical or radiographic suspicion of vascular injury. PMID- 2212569 TI - Chest injury with complication in a 30-year-old man following a motor vehicle accident. PMID- 2212570 TI - Observation units: boom or bust for emergency medicine. AB - Observation units (OBS) are becoming a common addition to the emergency department. The diagnostic and socioeconomic categories of patients admitted to the OBS unit resemble those seen in the emergency department. There are many advantages and disadvantages in establishing such a unit. Although OBS units provide improved patient care, current difficulties in reimbursement may delay their widespread acceptance. PMID- 2212571 TI - Emergency department ultrasound: is it really time for real time? PMID- 2212573 TI - Observation units: boom or bust for emergency medicine. PMID- 2212572 TI - An observation unit--essential to the safe and effective practice of emergency medicine. PMID- 2212575 TI - Therapeutic use of an electronic immobilization device. PMID- 2212574 TI - Observation units: another cause for early retirement of emergency physicians. PMID- 2212576 TI - Concerning drug interactions with theophylline. PMID- 2212578 TI - When your emergency department is busy it tends to get busier. PMID- 2212577 TI - The QBC2 analyzer in the emergency department. PMID- 2212579 TI - The emergency medicine resident as paramedic: a prehospital in-field rotation. AB - Prehospital care has undergone a significant evolution during the past two decades and has been transformed from a transportation service into an advanced life support (ALS) delivery system. Crucial to the quality of such a program is physician knowledge and medical control. We describe a formal, one-month prehospital rotation for emergency medicine residents. The resident physician is exposed to a number of varying emergency medical services (EMS) systems, administrative experiences, and most uniquely, functions as a paramedic within our own ALS EMS system. In this manner, we believe the resident best obtains an understanding of the environment, attitudes, and behavior of prehospital personnel. PMID- 2212581 TI - Infection control software. PMID- 2212580 TI - Objectives to direct the training of emergency medicine residents on off-service rotations: dermatology. AB - This is the fifth in a continuing series of objectives to direct resident training in emergency medicine. Approximately 50% of resident experience and training in emergency medicine takes place outside of the direct control and influence of full-time emergency medicine faculty. To gain some direction and control over these off-service rotations, objectives and references are offered here. Objectives for a dermatology rotation as well as contents and references are presented. PMID- 2212582 TI - Semi-automated infection control surveillance in a Veterans' Administration Medical Center. PMID- 2212584 TI - From the museum. PMID- 2212583 TI - Clostridium difficile-associated disease in long-term care facilities. PMID- 2212585 TI - Adjuvant radiation therapy in endometrial carcinoma. AB - Between 1983 and 1987, 79 patients received radiation therapy in combination with surgery for cancer of the endometrium. The pathology in all cases was adenocarcinoma. Most cases had deep myometrial penetration with moderate or poor differentiation. More than two-thirds of the patients had stage I disease. Twenty two patients received preoperative radiation, and 57 patients received radiation following surgery. There were 10 recurrences in the 79 patients treated. Most recurrences were from distant disease, and there was only one case of an isolated pelvic recurrence. Adjuvant radiation is well-tolerated, and the failure rate in the pelvis is low, even with aggressive lesions. PMID- 2212586 TI - Mediastinal mass in a patient with lymphoma. PMID- 2212587 TI - Flexor carpi radialis tunnel syndrome. PMID- 2212588 TI - The role of the physician in identifying and treating abused women. PMID- 2212589 TI - Update on legal processes for adoption in Indiana. AB - In this article, we review the process of adoption in Indiana. Comments about the legal process, the right to know issue and the process of adoption from the viewpoint of the potential adoptive parents are discussed. PMID- 2212590 TI - Antibiotic prophylaxis for dental patients with prosthetic joints. PMID- 2212591 TI - ISBH approves expanded AIDS group membership. PMID- 2212592 TI - AIDS videotape designed to promote understanding. PMID- 2212593 TI - Osteomyelitis. A symposium on Bone and Joint Infections--New Perspectives. Pittsburgh, October 12-13, 1989. Proceedings. PMID- 2212594 TI - Epidemiology in bone and joint infection. AB - The studies of community-acquired infection indicate the importance of the environment in which the host-pathogen interaction takes place. Whereas the high incidence rates at the extremes of life are compatible with a hypothesis of diminished immune competence, the varying rates of acute osteomyelitis during growth, and its predominantly metaphyseal site, suggest that further studies of the molecular biology of this rather specific infection would be revealing. Molecular biology has a role, too, in improving understanding of the epidemiology of resistance and pathogenicity in hospital-acquired infections. Although antibiotic prescription and other medical practices influence the environment profoundly, we should remember that we may be experiencing long-term trends beyond our present understanding. As more and more reconstructive bone and joint surgery is carried out, careful observational epidemiology remains a vital tool. PMID- 2212595 TI - Animal models of osteomyelitis. Knowledge, hypothesis, and speculation. AB - Each animal model has provided insights. Particularly important was the considerable resistance of bone to infection without manipulation (no morrhuate, fracture, rod, wax, or prosthesis). Such perturbations allow bone infection with much smaller inocula. Typical inocula decreases are 1000 to 10,000 fold. Staphylococci may have a selective advantage in bone because of specialized or tropic binding, perhaps to cartilage or collagen. Osteoclast-induced resorption of hydroxyapatite might explain the distribution of some osteomyelitis. Increased osteoclast activity could link the susceptible metaphyseal regions, the repetitively traumatized diabetic foot, a history of blunt bone trauma, fracture, and perhaps even nearby soft tissue infection. Diagnosis remains difficult; gallium-67 and indium111 labeled WBC probably deserve additional investigation. Therapeutic failures in the rabbit and rat models mirror clinical experience. Clindamycin, rifampin, and quinolones are promising. Neither systemic nor local antimicrobial prophylaxis is well studied yet. PMID- 2212596 TI - Musculoskeletal infection, microbial adhesion, and antibiotic resistance. AB - Osteomyelitis and intra-articular infection are septic diseases that present pathogenic features characteristic of molecular mechanisms involving adhesion to substrata. In this review, mechanisms of microbial adhesion to bone and cartilage as substrata are presented and related to host tissue response and to antibiotic treatment. PMID- 2212597 TI - The diabetic foot. Soft tissue and bone infection. AB - Diabetic patients, as a consequence of various neurologic, vascular, and metabolic perturbations, are at high risk for developing infections of the soft tissue and bones of the feet. The microbial etiology of soft tissue in infections is best determined by cultures of a tissue curetting or aspiration, rather than a swab. Aerobic gram-positive cocci are the major pathogens in diabetic foot infections; these may be the sole isolate(s) in acute uncomplicated infections, but they are usually accompanied by aerobic gram-negative bacilli or anaerobes in chronic or previously treated infections. Carefully selected patients with mild infections can be treated as outpatients with oral antibiotics, but others require hospitalization and broad-spectrum parenteral antibiotics. Bone infections are frequently diagnosed on the basis of roentgenographs and nuclear medicine scans, but these methods are often inaccurate, and bone cultures should be obtained whenever possible. PMID- 2212598 TI - Hyperbaric oxygen as adjunctive therapy for osteomyelitis. AB - Mechanistically, hyperbaric oxygen (HBO) appears useful for the treatment of osteomyelitis. HBO increases the oxygen tension in infected tissue, including bone. An adequate oxygen tension is necessary for oxygen-dependent killing of organisms by the polymorphonuclear leukocytes and for fibroblast activity leading to angiogenesis and wound healing. HBO has a direct bacteriocidal or bacteriostatic effect on anaerobic organisms. In addition, HBO augments the killing of Pseudomonas aeruginosa by the aminoglycoside--tobramycin. At the University of Texas Medical Branch at Galveston, adjunctive HBO is used for the Cierny Mader stage 3B and 4B osteomyelitis. PMID- 2212599 TI - Diagnostic imaging of osteomyelitis. AB - There are many imaging procedures for diagnosing osteomyelitis, each with unique strengths and weaknesses. Plain radiographs are inexpensive and can be very accurate but may provide a delayed diagnosis. Computed tomography and magnetic resonance imaging are both excellent at differentiating soft tissue infection from osteomyelitis. Computed tomography, magnetic resonance imaging, and bone scans are accurate diagnostic tools for use when the bone has not be violated by surgery, trauma, or other structural alterations. When such changes are present, an Indium-111 leukocyte or Indium-111 polyclonal antibody study may be necessary for accurate diagnosis. PMID- 2212600 TI - Infection in total joint replacement. AB - Although a small number of infections in total joint replacements are blood borne from distant sources, most infections appear to have been derived at operation. Strenuous attempts to reduce this risk by cleaning the air in the wound environment, coupled with prophylactic antibiotics, have reduced infection rates by an order of magnitude in a decade. During that time the potential for exchange arthroplasty in established infection has been shown, and the results are encouraging. Rigorous infection control is the key to containing this difficult and expensive problem. PMID- 2212601 TI - Antibiotic therapy for osteomyelitis. AB - Antibiotic therapy for osteomyelitis has dramatically changed within the past twenty years. The diagnostic criteria for osteomyelitis remain confusing to practicing physicians. Bone biopsy culture is now the standard for determining specific antimicrobial therapy. Many of the newest and most potent antimicrobials are now used to treat the increasingly broad bacterial spectrum of etiologies of osteomyelitis. There are tremendous economic incentives for outpatient and/or oral therapy. The third-generation cephalosporins and the new fluoroquinolones have replaced older, more toxic regimens, especially those containing aminoglycoside used to treat gram-negative osteomyelitis due to susceptible organisms. PMID- 2212602 TI - Surgical approaches in osteomyelitis. Use of laser Doppler flowmetry to determine nonviable bone. AB - The surgical management of osteomyelitis includes radical debridement on nonviable bone. Laser Doppler flowmetry is a method for directly assessing the functional microcirculation in bone. The early results of the use of this technique as a surgical adjunct in the management of osteomyelitis are promising. PMID- 2212603 TI - Acute osteomyelitis in children. AB - Although relatively uncommon, osteomyelitis is an important disease because of the potential for chronicity or permanent sequelae. Diagnostic methods, the spectrum of the disease, and clinical situations that merit special consideration are reviewed in this article. PMID- 2212604 TI - Infectious arthritis. AB - Any patient who presents with an acute monarticular arthritis, especially a new asymmetric effusion with underlying joint disease, should be suspected of having a bacterial process. Because synovial fluid findings (leukocyte counts and glucose) may not be predictive of infection, bacteriologic analysis by smear and culture is necessary in the evaluation of any new synovial effusion. A chronic monarticular process is highly likely to be infectious also, but mycobacterial or fungal etiologies frequently require appropriate culture of synovial tissue in addition to processing fluid. Acute polyarticular syndromes are seen as manifestations of disseminated gonococcal infections (DGI) and certain viral infections in adults. Diagnostic clues include historic and physical findings (exposure history and type of rash). The major pathogen in adults remains Staphylococcus aureus, so initial therapy is directed at this organism unless urinary tract infection is present also. Proper recommended therapy for DGI is ceftriaxone because penicillin-resistant strains are present in many urban centers. Early recognition and treatment of bacterial arthritis may prevent poor outcome, particularly in elderly patients or those with underlying joint diseases. For chronic mycobacterial or fungal infections, surgery may need to be combined with medical management. PMID- 2212605 TI - Vertebral osteomyelitis. AB - Vertebral osteomyelitis can be caused by a variety of microorganisms. The hematogenous pyogenic form is characteristically a disease of people over age 50, predominantly in the male population, and most frequently caused by S. aureus. In IVDAs, however, younger patients and a heavier predominance of males are seen, and P. aeruginosa is one of the most commonly seen pathogens. The disease is generally monomicrobial, unless it is secondary to a contiguous process such as a pressure sore, in which polymicrobial infection with participation of anaerobes is the general rule. Lumbar, greater than thoracic, greater than cervical involvement is the rule in the general population, but cervical spine involvement is frequently seen more often than thoracic involvement in IVDAs. Diabetic patients are over-represented among patients with vertebral osteomyelitis, and they also have a tendency for higher morbidity and mortality. Simultaneous involvement of adjacent vertebral end plates and the intervening disk is the general rule. The vertebrae are generally involved, and the posterior elements of the spine are involved infrequently. Posterior element involvement is seen more commonly in actinomycosis, coccidioidomycosis, and neoplasms. Newer diagnostic modalities, such as CT, MRI, and radionuclide scans, may detect the disease earlier than conventional radiographs. Immunobilization by bed rest and appropriate antimicrobial therapy are generally sufficient in the therapy of pyogenic, as well as tuberculous, vertebral osteomyelitis. In selected circumstances, such as in the presence of marked instability of the spine, the presence of new neurologic deficits, or with progression of previous neurologic deficits, surgical intervention may be necessary. With prompt diagnosis and proper management, the prognosis should generally be good. PMID- 2212606 TI - The responsible medical historian. PMID- 2212607 TI - Interpreting the Fasciculo anatomy scene. PMID- 2212608 TI - Pasteur, Roux, and rabies: scientific versus clinical mentalities. PMID- 2212609 TI - The historical decline of tuberculosis in Europe and America: its causes and significance. PMID- 2212610 TI - Of grandes dames, surgeons, and hospitals: Batavia, New York, 1900-1940. PMID- 2212611 TI - Moving reprints: a historian looks at sex research publications of the 1930s. PMID- 2212612 TI - The origins of Mount Sinai School of Medicine. PMID- 2212613 TI - Immunolabeling efficiency of protein A-gold complexes. AB - A systematic study of the adsorption of protein A on colloidal gold particles varying in size from 5-16 nm was performed at different protein concentrations. The number of protein A molecules bound per colloidal particle was evaluated and the Scatchard analysis of the adsorption parameters was applied for each size of the colloid. The binding of protein A to the colloidal gold surface exhibited the same affinity pattern for all of the particle sizes. At low concentrations of stabilizing protein, adsorption took place with high affinity (Kd 1.96-3.3 nM) and the maximum number of protein A molecules attached with this affinity correlated well with the surface of the particle. At higher concentrations of protein A, adsorption exhibited a significantly lower affinity (Kd 530-800 nM), and no saturation was recorded. Competition by albumin did not reveal a preferential removal of the "low-affinity" bound protein A molecules, contradicting the model of successive shells of stabilizing protein around the colloidal particle. The immunolabeling efficiency of conjugates having the same size of gold nucleus but carrying different numbers of protein A molecules was comparatively investigated by quantitative post-embedding immunocytochemistry. Protein A-gold formed with 5-10-nm colloids gave the highest intensity of labeling when carrying the maximum number of protein A molecules that could be adsorbed with high affinity. Overloading as well as underloading these complexes resulted in a significant decrease of their immunoreactivity. The most efficient conjugates were obtained when stabilization was performed with 6 micrograms protein A/ml gold sol of 5 and 10 nm particle diameter, and 15 micrograms protein/ml of 15-nm colloid. PMID- 2212614 TI - Magainin-like immunoreactivity in human submandibular and labial salivary glands. AB - Magainins, antimicrobial peptides secreted by granular glands of frog skin, may be related to the high resistance to infections of this epithelial surface. The oral mucosa of healthy individuals is another tissue in which infection is not frequent, probably owing to the activity of potent salivary and mucosal defense mechanisms. To investigate if magainin-like factors are a component of these oral defense mechanisms, human and animal minor (mucosal) and major salivary glands were examined by immunohistochemistry, using a polyclonal rabbit anti-magainin antibody. Cryostat sections of (para) formaldehyde-fixed tissues were incubated with the antibody and then stained with fluorescein-complexed anti-rabbit IgG. Specific staining was observed in the apical portion of the cytoplasm of ductal epithelial cells of human submandibular and labial salivary glands. Diffuse staining was present in submandibular acinar cells. Bovine, rat, hamster, and mouse tissues were unreactive. The presence of magainin-like substances in human salivary gland duct cells is consistent with reports of the occurrence of other biologically active substances in salivary gland ducts. PMID- 2212615 TI - Immunocytochemical identification of proliferating cell types in mouse mammary gland. AB - To study cell proliferation in different cell types and segments of the mammary gland, we devised a dual staining procedure, combining nuclear labeling by 5 bromo-2'-deoxy-uridine (BrdU) uptake (revealed by a dark-brown precipitate) and an alternative (red or blue) cytoplasmic labeling by antibodies specific for the differentiation proteins of epithelial, myoepithelial, and secretory cell types. The following markers, revealed by APAAP or beta-galactosidase procedure, were selected: alpha-smooth muscle actin for the myoepithelial cells, keratin (detected by AE1 monoclonal) for the luminal epithelial cells, alpha-lactalbumin and beta-casein for the secretory cells. To follow the full process of organogenesis, the study was conducted in mouse mammary glands from virgin, primed, and lactating animals and from glands cultured in vitro under specific hormone stimulation. Cell proliferation was localized mainly in focal areas (end buds), and mostly corresponded to "null" undifferentiated cells. Estrogen and progestin stimulation induced a relative increase of proliferating differentiated cells of either epithelial or myoepithelial type, localized in ducts and alveolar structures. Prolactin stimulation induced proliferation in secretory cells. PMID- 2212616 TI - Expression and localization of the two small proteoglycans biglycan and decorin in developing human skeletal and non-skeletal tissues. AB - The messenger RNAs and core proteins of the two small chondroitin/dermatan sulfate proteoglycans, biglycan and decorin, were localized in developing human bone and other tissues by both 35S-labeled RNA probes and antibodies directed against synthetic peptides corresponding to nonhomologous regions of the two core proteins. Biglycan and decorin expression and localization were substantially divergent and sometimes mutually exclusive. In developing bones, spatially restricted patterns of gene expression and/or matrix localization of the two proteoglycans were identified in articular regions, epiphyseal cartilage, vascular canals, subperichondral regions, and periosteum, and indicated the association of each molecule with specific developmental events at specific sites. Study of non-skeletal tissues revealed that decorin was associated with all major type I (and type II) collagen-rich connective tissues. Conversely, biglycan was expressed and localized in a range of specialized cell types, including connective tissue (skeletal myofibers, endothelial cells) and epithelial cells (differentiating keratinocytes, renal tubular epithelia). Biglycan core protein was localized at the cell surface of certain cell types (e.g., keratinocytes). Whereas the distribution of decorin was consistent with matrix-centered functions, possibly related to regulation of growth of collagen fibers, the distribution of biglycan pointed to other function(s), perhaps related to cell regulation. PMID- 2212617 TI - Absence of cytochrome P-450 and presence of autolysosomal membrane antigens on the isolation membranes and autophagosomal membranes in rat hepatocytes. AB - We wished to determine if phenobarbital (PB)-inducible cytochrome P-450 [P 450(PB)] and autolysosomal membrane antigens could be localized immunocytochemically on the isolation membranes and the limiting membranes of autophagosomes in rat hepatocytes by the post-embedding protein A-gold method. P 450(PB) was maximally induced by PB treatment; then formation of autophagosomes and accumulation of autolysosomes were induced by cessation of PB treatment and by injection of leupeptin, respectively. P-450(PB) was detected neither on the isolation membranes nor on the limiting membranes of autophagosomes and autolysosomes. Autolysosomal membrane antigens, which were localized by the immunogold technique exclusively in post-Golgi compartments such as lysosomes, endosomes, and plasma membrane but were not found in pre-Golgi compartments such as endoplasmic reticulum (ER) and nuclear envelope, were detected in large amounts on the isolation membranes. These results suggest that the isolation membranes originate not from ER membranes but from post-Golgi membranes. We also present direct immunoelectron microscopic evidence that P-450(PB) is indeed degraded in the autolysosomes: when rats were treated with leupeptin, P-450(PB) was detected not only within the autophagosomes but also within the autolysosomes, whereas without leupeptin treatment, P-450(PB) was detectable only within the autophagosomes. PMID- 2212618 TI - Detection of S-100b protein in Triton cytoskeletons: an immunocytochemical study on cultured Schwann cells. AB - We investigated the subcellular distribution of S-100b protein in primary cultures of Schwann cells. The subcellular localization of the protein in cells fixed and then permeabilized is similar, if not identical, to that seen in Schwann cells in peripheral nerves, i.e., S-100b protein is found in the cytoplasm and associated with membranes and filamentous structures. In cells either fixed in the presence of Triton X-100 or exposed to Triton X-100 for a short time before fixation (Triton cytoskeletons), the immune reaction product is considerably less intense, and the protein is associated with filaments running parallel to the long axis of the cell as well as in a submembranous position. Including CaCl2 in the buffer during fixation in the presence of Triton X-100 does not result in any increase in the intensity of the immune reaction product in Triton cytoskeletons, suggesting that, within the limits of the technique employed, no binding of additional S-100b protein to the Triton X-100-resistant material can be induced. On the other hand, including EGTA results in a substantial decrease in the intensity of the immune reaction product in Triton cytoskeletons. Altogether, these findings suggest that a remarkable fraction of S 100b protein in cultured Schwann cells is associated with elements of the cytoskeleton and that Ca2+ exerts some regulatory role in the association of S 100b protein with the cytoskeleton. PMID- 2212619 TI - Microphotometric analysis of cytochrome P-450 in periportal, midzonal, and perivenular hepatocytes of mice treated with phenobarbital. AB - To obtain detailed information on the increase of cytochrome P-450 (P-450) content in periportal, midzonal, and perivenular hepatocytes after phenobarbital (PB) administration, and to study the mechanism of increased P-450 in the endoplasmic reticulum (ER), we estimated microphotometrically the P-450 content and morphometrically the area of ER in hepatocytes of three zones from mice injected with 35, 50, 100, or 150 mg/kg of PB for 3 days. The amount of P-450 per unit cytoplasmic volume and the number of P-450 molecules per unit ER area (P-450 number) were increased by injection of 50, 100, or 150 mg/kg, and the ER area per unit cytoplasmic volume was increased by injection of 100 or 150 mg/kg, in hepatocytes from all three zones. Thus, the amount of P-450 in hepatocytes appeared in general to increase multiplicatively by simultaneous increases in both the P-450 number and the ER area. Furthermore, we could recognize two general types of relationship in the P-450 number and ER area between the patterns of change and the increasing doses: (a) increase in the P-450 number without ER proliferation (active type) in periportal and perivenular hepatocytes after injection of low doses; and (b) increase in ER proliferation without increase in the P-450 number (passive type) in hepatocytes of all three zones after injection of high doses. PMID- 2212621 TI - Appearance of myoepithelial cells in developing rat mammary glands identified with the lectins Griffonia simplicifolia-1 and pokeweed mitogen. AB - The histochemical binding of peroxidase-conjugated Griffonia simplicifolia-1 (GS 1) and pokeweed mitogen (PWM) to methacarn-preserved and paraffin-embedded female rat mammary glands at different developmental stages has been undertaken with a view to investigating the ontogeny of the myoepithelial cell. Conjugated GS-1 fails to stain the outer layer of ductal cells in neonatal rats up to 3 days old, but thereafter the staining increases so that all such cells are intensely stained in rats 5 days old and in mature, pregnant, and lactating rats. Conjugated GS-1 also stains most of the inner epithelial cells that line the ducts in neonatal rats up to about 5 days after birth; thereafter no such cells are stained in mature, pregnant, and lactating rats. Conjugated PWM stains both the inner and outer cell layers of ducts in neonatal rats up to 5 days old; thereafter the fraction of strongly stained cells declines rapidly in both cell layers so that in 6-day-old rats only weak staining is visible. Staining with PWM continues to decline for the inner epithelial cells of the ducts until it ceases when the rats mature; in contrast, that for the outer cell layer of the ducts increases so that all such cells are stained intensely when the rats mature. This pattern of ductal staining with PWM is maintained for pregnant and lactating rats. In terminal end buds of mammary ducts of prepubertal rats, GS-1 binds mainly to the peripheral or cap cells, the staining intensity increasing from cap cells at the distal tip to myoepithelial cells of the subtending duct. PWM binds to many more of the cortical epithelial cells and fewer of the cap cells. At the ultrastructural level, cap cells and adjacent immature myoepithelial cells both bind GS-1 and PWM to their surfaces, but basal clear cells do not. In alveolar buds and in alveoli, both conjugated lectins GS-1 and PWM bind to myoepithelial cells but not to epithelial cells of the rat mammary gland. We suggest that the appearance of carbohydrate receptors for GS-1 and PWM marks specific stages of myoepithelial cell differentiation in developing rat mammary glands. PMID- 2212620 TI - Binding of T-antigen-bearing neoglycoprotein and peanut agglutinin to cultured tumor cells and breast carcinomas. AB - Chemical conjugation of appropriate carbohydrate ligands to an inert labeled carrier renders probes available to screen for the presence of respective binding sites. A set with a certain plant lectin and a suitable neoglycoprotein can thus determine complementary parts of a potentially relevant glycobiological interaction system. Owing to the interest in the peanut agglutinin-reactive T antigen, we performed chemical synthesis of the respective disaccharide structure to serve as glycohistochemical ligand and established refinements of the synthetic patway. Coupling of the derivatized monomers had to be performed in the presence of sodium sulfate for optimal results. Complete removal of the protective groups from the p-nitrophenyl derivative of the N-acetylgalactosamine moiety was achieved under mild conditions with 2,3-dichloro-5,6 dicyanobenzoquinone without affecting any other functional groups. Specific binding sites for the synthetic neoglycoprotein as well as for the plant lectin were demonstrated in cell lines of human breast carcinoma colon adenocarcinoma, and erythroleukemia. ABC reagents in conjunction with DAB as peroxidase substrate were used to visualize specific binding sites. Binding complied with the accepted criteria for specificity. Moreover, carbohydrate-specific binding sites were detected in sections of nine out of 14 cases with malignant breast lesions. The percentage of positive tumor cells with both neoglycoprotein and lectin was similar in each of the individual sections, regardless of quantitative variations between cases, lectin staining intensity often being more pronounced. The reactivity pattern in sections of primary and metastatic lesions was not significantly correlated with the lymph node status. This study emphasized that custom synthesis of saccharides and histochemical application of the resulting neoglycoprotein has a remarkable potential for complementary assessment of endogenous binding sites for carbohydrate structures, localized by external tools such as plant lectins, as a step to elucidate the importance of a putative proteincarbohydrate interaction. PMID- 2212622 TI - Multimarker immunohistochemical staining of calgranulins, chloroacetate esterase, and S100 for simultaneous demonstration of inflammatory cells on paraffin sections. AB - Mac387 monoclonal antibody (MAb) recognizes two calcium binding, myeloid associated proteins, now termed calgranulins, expressed at high levels by neutrophils and monocytes. Calgranulins are related to migration inhibitory factor (MIF) and are lost in a few days from monocytes differentiated in vitro. This marker is therefore potentially useful to analyze macrophage heterogeneity and turnover in tissue sections. In this study, we developed an immunohistochemical multimarker technique, including calgranulin demonstration, suitable for analyzing different inflammatory cells on paraffin-embedded material. The technique was carried out in subsequent steps demonstrating (a) naphthol AS-D chloroacetate esterase (CAE); (b) S100 immunoreactivity using a rabbit antibody in peroxidase-antiperoxidase (PAP) staining; and (c) Mac387 immunoreactivity using the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique. CAE staining was introduced in this method to distinguish Mac387+/CAE- macrophages from Mac387+/CAE+ neutrophils, and Mac387-/CAE+ mast cells. S100 protein is strongly expressed within lymphoid tissues by dendritic accessory cells and was then applied to distinguish these cells from S100-macrophages. We have also verified the possibility of reducing the staining time for this time consuming procedure by use of microwave irradiation. The technique was applied to a representative variety of normal and pathological samples to assess its usefulness for study of cell heterogeneity. Our results showed the multimarker technique to be highly informative in the study of inflammatory lesions (e.g., rheumatoid arthritis, sarcoid and cat-scratch granulomas, dermathopathic lymphadenopathy), and is of wide potential value as an aid to histopathological diagnosis of several diseases. PMID- 2212623 TI - An improved staining method for rat microglial cells using the lectin from Griffonia simplicifolia (GSA I-B4). AB - A simple method for the lectin histochemical visualization of rat microglial cells is described. Advantages include ease of fixation of brain tissue using paraformaldehyde, and rapidity of tissue processing by vibratome sectioning. Furthermore, in addition to providing good structural preservation, the method achieves improved lectin binding, resulting in complete labeling of all microglial cells and in superior visualization of cellular processes. The lectin histochemical technique for rat microglia has the potential to be adapted to any mammalian species, and should prove valuable for neuroscientists interested in studying this glial cell type. PMID- 2212625 TI - Immunocytochemical demonstration of vasopressin binding in rat kidney. PMID- 2212624 TI - Effect of resin use in the post-embedding procedure on immunoelectron microscopy of membranous antigens, with special reference to sensitivity. AB - To investigate quantitatively the effect of resins on the sensitivity of immunoelectron microscopy of membranous antigen, ultra-thin sections of bovine epithelial tissue embedded in five different kinds of resins [JB-4 (JB4), LR Gold (LRG), Lowicryl K4M (K4M), Quetol 812 (Q812), and Spurr's (Spurr) resin] were labeled specifically with anti-desmosomal glycoprotein I(DGI) antibody followed by protein A-gold (PAG) conjugates. When we compared the labeling intensity expressed as the number of PAG particles per 500-nm length of the desmosomal region along the membrane, three hydrophilic resins (JB4, LRG, and K4M) showed much greater levels of labeling intensity than did epoxy resins (Q812 and Spurr), which had a negative value. The three hydrophilic resins showed only minor differences in their levels of labeling intensity. The intensity obtained with JB4, which was the highest of the three, was further increased by pretreatment of the ultra-thin sections with methyl methacrylate monomer (MM) for 5 min. On the basis of these results, wide applicability of this new technique for membranous antigens, which have been difficult to detect positively by any previously employed techniques, is suggested. PMID- 2212626 TI - Power-sharing in lesbian partnerships. AB - This study of 70 lesbian couples explored whether partners who characterized certain aspects of their relationships as equal in power-sharing were similar in age, income, education, and financial assets, while those who viewed their power sharing as unequal would be dissimilar on these social status variables, and, second, whether or not most lesbian couples considered their relationships as egalitarian. Power-sharing was assessed through a number of questionnaire items, and snowball sampling was utilized. Three types of couples emerged: (a) equal, (b) unequal but in agreement about who had more power, and (c) couples with differing perceptions about power-sharing. The findings indicated that power sharing arrangements could not be explained by age, income, education, and asset differences between partners. Egalitarianism was the ideal in most relationships, but had not been achieved to the same degree in each of the areas investigated. PMID- 2212627 TI - AIDS victims and heterosexual attitudes. AB - This study reports on the development of a Likert scale that measures attitudes toward AIDS victims (ATAV) in five phases. A total of 582 undergraduate (means age = 24.2) completed the survey forms, 249 males and 333 females. The results for Phase 1 yielded a scale with high part-whole correlations (.62-.90, p less than .001), corrected split-half reliability (.87, p less than .001), and alpha coefficients (.91, p less than .001). The following phases yielded significant correlations between the ATAV scale and attitudes toward homosexuals (.60, p less than .001), homosexual parenting (.64, p less than .001), other minority groups (.33, .37, p less than .001), capital punishment (-.27 p less than .001), and sexually liberal attitudes (.22, .37, .23, p, less than .025). Attitudes toward homosexuals are the central component in attitudes toward AIDS victims. A varimax rotated factor analysis of the ATAV yielded one primary factor accounting for 85.9% of the variance. PMID- 2212628 TI - Attitudes towards homosexuality in American health care literature 1983-1987. AB - The purpose of this paper was to content analyze a purposive sample of American health care literature from 1983-1987 to ascertain what impact if any, the AIDS epidemic has had on the images of gay men and lesbian women in health sciences literature. Empirical studies, letters to the editor, policy statements and opinion papers expressing attitudes towards homosexuality and psychosocial aspects of AIDS in nursing, general medicine, and psychiatric literature were content analyzed. Findings indicate that although positive, neutral and negative images were found in the 59 articles which were examined, the largest proportion (61%) were negative. This reflects a change in the literature from previously neutral positions. Implications for patient care and further research are addressed. PMID- 2212629 TI - Men together: understanding the gay couple. AB - The present study surveyed male gay couples to determine how their relationships began and were maintained, the types of conflict they experienced, and how the issues of monogamy, sexual behavior and AIDS affected the relationships. Ninety two couples responded to the survey. The gay bar was the most common initial meeting place and relationships had lasted from less than one to 35 years. Few had had a commitment ceremony, although many reported wanting one if it were available. Most of the close friends of respondents were also gay couples and about two-thirds of family members were supportive of the relationship. The most persistent conflicts centered around finances and relations with family members. Virtually all respondents described their relationships as monogamous, but only about half practiced safe-sex. More attention needs to be given to understanding male couples and to targeting AIDS-prevention messages to them. PMID- 2212630 TI - Substance use as a correlate of violence in intimate lesbian relationships. AB - This article examines the problem of domestic violence as related to substance abuse in lesbian relationships. One hundred and four self-identified lesbians responded to a 70-item mail survey. Thirty-nine reported a past or present abusive relationship. Sixty-four percent reported alcohol or drugs were involved prior to or during incidents of battering. Respondents' frequency of drinking significantly correlated with committing abusive acts as well as with being the victim of abusive acts. Efforts must be initiated to improve the delivery of human services to lesbian batterers and victims and to encourage cooperation and cross-fertilization between practitioners from the domestic violence and substance abuse fields. PMID- 2212631 TI - The relationship between culture, personality, and sexual jealousy in men in heterosexual and homosexual relationships. AB - This study proposes a new approach to sexual jealousy, that of attitude theory. Within that framework, it examines the roles of culture and personality in the development of sexual jealousy. Using 194 men representing 62 male homosexual couples and 81 heterosexual couples, three hypotheses were analyzed: (1) that jealousy measured by a standard attitude measure, the semantic differential technique, will significantly positively correlate with scores on a standard jealousy measure, Eugene Mathes' Interpersonal Jealousy Scale; (2) that men in heterosexual couples will have higher levels of sexual jealousy than men in homosexual couples; and (3) that sexual jealousy is inversely correlated with self-actualization personality. All three hypotheses were supported, suggesting that sexual jealousy, viewed as an attitude, is mediated by culture and personality. PMID- 2212632 TI - The stigma of AIDS: fear of disease and prejudice toward gay men. AB - Three hundred college students were presented with vignettes describing an ill person; the vignettes were identical except the illness was identified as either AIDS or leukemia and the individual was described as either homosexual or heterosexual. After reading one vignette, each subject completed a set of measures sensitive to interpersonal evaluation, prejudicial attitudes, and willingness to interact casually with the portrayed individual. The findings indicate the presence of highly stigmatizing attitudes towards AIDS patients and suggest that the public views AIDS patients and gay persons with similar attitudinal prejudice. The need for greater attention to AIDS by social and behavioral researchers is discussed. PMID- 2212633 TI - Electroretinography in the diagnosis of thallium intoxication. AB - Appearance of dystrophic alterations in the retina was carried out by administering 0.2 ml 12 mM of tallium chloride solution into the vitreous humour of 9 rabbits. Electroretinographic examination revealed a decline in the b wave either decreasing 2-3 times or entirely disappearing as early as on day 2 after the administration of tallium chloride. Electron microscopic investigation suggested that photoreceptors of the retina were initial by involved in the pathological process. Namely, the external segments of the photoreceptors were found to be reduced, indicating impairment of the formation of photoreceptor disks, which is known to proceed continuously under normal conditions. In the absence of an electroretinogram (ERG), the photoreceptor layers were shown to have disappeared completely. An examination of 28 subjects who were exposed to tallium and its compound at work revealed impaired retinal electrogenesis, as evident from subnormal ERG responses. This was of a functional nature and became more pronounced as occupational exposure time increased. The fact that the internal retinal layers and the 3-rd neurone remained intact, as suggested by the electrical sensitivity of the eye and lability of the optic nerve as well as by static perimetry, correlated with the EM findings obtained in experiments. Ophthalmobiomicroscopic examination of 12 eyes yielded data on characteristic changes in the lens when visual functions remained intact. These findings suggest that changes in the ERG may be indicative of initial preclinical symptoms of tallium intoxication and as such can be used when persons exposed to it in industry receive check-ups. PMID- 2212634 TI - Hygienic examination of the stimulating effect on the organism of a complex of natural substances. AB - No exhaustive hygienic studies have been conducted yet of the natural substances present in the atmosphere. A complex of natural substances was shown to affect EEG parameters, subjective perception of one's health and general perception. The concentration of the vapours of a mixture of substances was kept at 0.1 mg/m3 which is characteristic of mountainous air. The inhalation of the natural substances was shown to alter the EEG indicators and subjective perception of tested subjects, suggesting a stimulatory effect on the central nervous system. The natural substances proved to stimulate the efficiency of mental and manual work, self-perception and mood. These effects can be accounted for by the positive biological influence of the mountainous atmosphere. PMID- 2212635 TI - Effect of prior eradication of Plasmodium berghei infection on the foetal development and parasitaemic levels under the stress of pregnancy. AB - Pregnant mice infected on gestation day (GD) 13 with Plasmodium berghei had similar rate of parasitaemia and mortality as non pregnant controls. 50% of pregnant infected mice had normal delivery, 20% had absorbed foetuses and 30% died before parturation. However, animals infected with P. berghei, treated with drugs (sulfadiazine or chloroquine) had normal foetal development. No recrudescence occurred in either of these groups of animals even under the stress of pregnancy indicating protection. Pups born to pregnant infected mice (GD) 13 had low body weight as compared to pups born to mice which were infected and treated with drugs. Histopathological findings showed hyperplasia of trophoblast and plugging of placental sinusoids with parasitized erythrocytes in animals infected on GD 13 only. It is felt that prior eradication of malaria infection results in development of sufficient immunity which prevents the mal development of foetuses or parasitaemic levels under the stress of pregnancy. PMID- 2212636 TI - The AIDS epidemic: profiles of development. AB - As all HIV-infected subjects become virus carriers, the epidemic will not attain a "steady state" until the number of deletions (from death and other factors) equals or outnumbers that of new cases, i.e. each HIV-infected subject transmits the infection to only one subject in the course of his lifespan. A full stop of all spreading of HIV will most likely require worldwide vaccination. By simple mathematical models it is shown that calculation of the number of HIV infected individuals based on the number of AIDS cases is very uncertain. The ratio of HIV infected subjects to AIDS cases is greatly influenced by the length of the incubation period and the case doubling time. Since the growth of the epidemic is exponential, all efforts to control the epidemic should be continuously intensified as single measures will only retard the rate of spread. The effect of saturation/deletion on the number of susceptible individuals is insignificant in this phase of the epidemic, except in small groups at special risk. PMID- 2212637 TI - Epidemiological analysis of acute respiratory disease (ARD) and characteristics of the influenza epidemic in Bohemia during the season 1986/1987. AB - The authors analyze the findings of epidemiological and virological surveillance of ARD in Bohemia during the season 1986/1987. In all, 57.5% of the Czech population was affected by acute respiratory disease (ARD). There were 5,950,832 cases reported, 124,444 complications (2.1% of the overall morbidity rate) and 5,374 deaths due to influenza, bronchitis, pneumonia and chronic pulmonary affection. The influenza epidemic commenced during the 48-th calendary week (CW) and lasted 5 weeks till the 52-nd CW. The epidemic was due to an influenza virus strain of the subtype A(H1N1) antigenically related to the drift variant A (Singapore) 6/86. Within an extremely short period of the epidemic, 1,094,865 influenza cases were reported and 22,313 cases of complications. 10.7% of the CSR population were affected during the epidemic in whose etiology noninfluenza respiratory viruses were significantly implicated, especially adenoviruses (41.7%) and the RS virus (26.9%). There was no excessive mortality in the course of the epidemic. The authors discuss the atypical nature of this particular influenza epidemic and the etiological role of respiratory viruses. PMID- 2212638 TI - Some epidemiological characteristics of pneumonia in Czechoslovakia and several neighbouring countries from the aspect of mortality rates. AB - The authors evaluated the dynamics of mortality rates due to pneumonia in Czechoslovakia and several neighbouring countries over the period of 1974 to 1985. The relative risk of death and proportional mortality rates were calculated and epidemiological curves plotted using data provided by the World Health Organization. It is concluded that during the period in question there was no positive change in the dynamics of mortality rates in Czechoslovakia. Particular attention should be paid to persons in the age group of 75 and more years, where the relative risk of death is at least 4 times greater than in the general population. PMID- 2212639 TI - Murine typhus on the northern Dalmatian islands, Yugoslavia. AB - The present epidemiological study had the objective to establish whether and to what extent resident islander populations might be affected by the natural foci of murine typhus. To this end, 294 serum specimens were collected during summer and autumn of 1985 from the northern Dalmatian islanders, all of which were tested for anti-Rickettsia typhi (R. typhi) complement fixing (CF) antibodies. These were detected and confirmed at both stages of the screening, namely during the first stage, conducted on the northern Dalmatian islands, where 63.3% of the representative population had a titre of 1:4 or higher and during the second stage, carried out on the island of Vir, with 68.1% of the residents found R. typhi positive unlike in the former. The majority of positive sera were found in the 21-60-year group, peaking in the 21-30- and 31-40-year groups with fewer positive sera among the subjects over 60 and the fewest among the residents below 20 years of life. Thus, current differences in antibody rates in various age groups were shown to be statistically significant. Murine typhus immunity in resident islander populations could be detected from the age of 10 years on, and was shown to become almost equal to the adult population's positive sera levels in the 16-20-year age group. No differences were revealed with regard to the infective agent exposure between the male and female populations representative of the total population or in any of the age groups. PMID- 2212640 TI - Comparative study of the prevalence and clinical profiles of diarrheas due to Aeromonas and other enteric pathogens. AB - The prevalence of Aeromonas spp. and other enteric pathogens in stool specimens from diarrheic and non-diarrheic patients was studied over a 12 month period (January to December, 1986). Except for the absence of fever, all the clinical features in Aeromonas diarrhea were comparable to those associated with other diarrheagenic agents. These features included abdominal pain (30%), vomiting (24.5%), fever (31.5%), dehydration (9.5%) and hematochezia (19.5%). Aeromonas spp. were more frequently isolated from patients with gastroenteritis (2.5%) than from control patients (1.0%) (P less than 0.05). Isolates were recovered more often during the dry months (66.7%), than during the wet months (33.3%). Among the enteric pathogens isolated, Aeromonas spp. (2.5%) ranked next to Esch. coli (14.5%) and Shigella spp. (6.3%) in prevalence. Other bacterial isolates included Plesiomonas shigelloides (1.5%) Vibrio spp. (1.0%), Yersinia enterocolitica (1.0%) and Salmonella spp. (1.8%). PMID- 2212641 TI - Microbiological diagnosis of suppurative-inflammatory processes of the E. N. T. organs and the maxillo-mandibulo-facial region under suspicion of anaerobic non clostridial infection. AB - The etiological role of non-sporulating anaerobic bacteria as causative agents of suppurative-inflammatory diseases (SID) of the maxillo-mandibulo-facial region and the E. N. T. organs as studied. Express diagnosis of anaerobic infection was carried out by means of gas-liquid chromatography. The species-specific composition of the microflora of the suppurative focus was investigated. It was established that only obligate anaerobes in monoculture or in association were isolated from patients with so-called "sterile" inoculations when strictly anaerobic bacteriological technique was used. The use of anaerobic bacteriological technique of investigation enlarged the spectrum of the microflora isolated from the suppurative focus from 5 to 26 species. Results of chromatographic and bacteriological examinations were compared; the main causes of obtaining false-positive and false-negative results of chromatography were analysed. Statistical processing using factor analysis has shown that the information power of chromatographic examination of the metabolites of anaerobic bacteria is higher in comparison with the main clinical-laboratory indices, but statistical processing using cluster analysis and correlation analysis has revealed that an index like metabolic activity reflects the degree of real participation of anaerobic microflora in the development of the pathological process, and can be used in the clinic for the evaluation of the degree of severity of the course of the SID and of the effectiveness of treatment. PMID- 2212642 TI - Studies on immunomodulatory properties of isoniazid. II. Effect of isoniazid on interleukin 2 production and interleukin 2-receptor expression. AB - The effect of isoniazid on interleukin 2 production and interleukin 2-receptor expression by phytohemagglutinin-stimulated human T cells was investigated. High concentrations of the drug decreased interleukin 2 production while low doses (10(-5)-10(-6) M) produced a slight increase in interleukin 2 production. Isoniazid did not affect the expression of interleukin 2-receptors on the surface of T cells, except a slight decrease in cells exposed to high levels of the drug. PMID- 2212643 TI - Dot-ELISA in detection of filarial antibodies: comparison with standard ELISA. AB - The present study deals with the preliminary results of two assays, standard ELISA and dot ELISA compared for their sensitivity in measuring humoral immune responses in filarial patients and normals residing in an area of bancroftian filariasis using a heterologous antigen. Responses were more vigorous in filarial patients than in endemic normals by both assays. Higher percentage of positivity and reciprocal titre of antibody were observed in dot ELISA showing more sensitivity than the standard ELISA. The dot ELISA method required only nanogram amounts of antigen. PMID- 2212644 TI - The effect of sodium nucleinate on allergic and immunological reactions. AB - Experiments on immunized rabbits and guinea pigs indicated that sodium nucleinate (SN) was capable of weakening or entirely eliminating anaphylactic and skin reactions of delayed type hypersensitivity to repeated administration of staphyloanatoxin, APDT vaccine. The findings on patients with the infectious form of bronchial asthma and chronic rheumatism showed that sodium nucleinate attenuated reactions to the subcutaneous administration of staphylococcal and streptococcal allergens. The treatment of patients suffering from infectious allergic bronchial asthma and rheumatism with SN resulted in the recovery of deficient T cells, T-suppressors, normalization of immunoglobulin concentrations. In children with acute glomerulonephritis sodium nucleinate normalized decreased T-suppressor cells and increased IgG and circulating immune complexes (CIC), resulting in a pronounced remission of disease. The mechanism of desensitization and elimination of CIC by SN has not been explored, however, the parameters of SN induced immunomodulation are known rather completely. It is suggested that SN brings about accumulation in the cell of cyclic AMP which diminished membrane permeability, activates monoaminooxidase resulting in the degradation of histamine and other biogenic amines, enhances the synthesis of endogenous corticosteroids with their desensitizing properties. All these effects contribute to the elimination of delayed type hypersensitivity. The role of SN in the inhibition of delayed type hypersensitivity remains obscure. PMID- 2212645 TI - Smallpox diagnosed 400 years later: results of skin lesions examination of 16th century Italian mummy. AB - Results are presented on virological examination conducted on WHO request of a Naples infant mummy with smallpox-like lesions. Electron microscopy of lesions confirmed the findings of Italian researchers: well-preserved virus-like structures, whose size and morphology were identical to those of orthopoxviruses have been revealed. It was shown that the virus in mummy skin had lost its viability. Viral antigenic activity could not be detected in EIA or RPHA, nor was determined its DNA in the test of DNA molecular hybridization. PMID- 2212646 TI - Polyclonal activation of rat B cells. II. Dextran sulfate as a cofactor in mitogen-induced and antigen-induced differentiation of rat B lymphocytes. AB - Salmonella typhimurium mitogen (STM) is a polyclonal activator of rat B lymphocytes, triggering them to proliferate, but not differentiate, to antibody secreting cells. When lymphokines in the form of a supernatant from Con A stimulated splenocytes (CAS) are added to B cell cultures activated by STM, only a small number of cells are driven to differentiate. Only with the addition of a third signal provided by the polyanionic polysaccharide dextran sulfate (DXS) is significant rat B cell differentiation observed. In this study, we have shown that this requirement for DXS is not unique to the STM mitogen. LPS, Staphylococcus aureus Cowan I-fixed cells, and anti-Ig antibody all induced rat B cell proliferation with little differentiation, even in the presence of CAS. DXS was necessary to induce differentiation in all cultures costimulated with mitogen and CAS. The requirement for DXS for optimal B cell differentiation is also observed with other lymphokine preparations such as the supernatants from PMA stimulated EL-4 cells and PHA-stimulated human T cells. Furthermore, this augmentative effect of DXS in rat B cell differentiation was not confined to polyclonal activation systems. Ag-specific IgG secretion was also increased when DXS was added to Ag and CAS costimulated cultures of B cells harvested from the draining lymph nodes of rats immunized with DNP-keyhole limpet hemocyanin. Within the polyclonal activation system, a method of staged additions of STM, DXS, and CAS to B cell cultures was used to investigate the role of DXS during B cell differentiation. Optimal differentiation occurred only when DXS was present in the B cell cultures in conjunction with CAS. The augmentation in differentiation seen with DXS did not appear to be due to the recruitment of an additional CAS responsive B cell subset, because cycling, low density B cell blasts showed large increases in IgM secretion with subsequent exposure to DXS and CAS. These studies suggest tha DXS acts as a cofactor to various differentiation factors, augmenting polyclonal and Ag-specific rat B cell differentiation. The relevance of DXS to in vivo immune responses is discussed. PMID- 2212647 TI - Germinal center cells are a major IL-5-responsive B cell population in peripheral lymph nodes engaged in the immune response. AB - Germinal center formation and the development of B cell memory in lymphoid tissue is a T cell-dependent process. The specific B cell-T cell interactions, and/or cytokines, resulting in germinal center cell growth have not yet been identified. Germinal center B cells were separated from other lymph node (LN) B cells by panning on peanut agglutinin (PNA)-coated dishes. Resulting fractions enriched for PNA+ (germinal center) B cells, and the PNA- (other) LN B cells from immune SJL mice were assayed for proliferation in the presence of cytokines. PNA+ and PNA- B cells responded equally to IL-4 in the anti-mu co-stimulator assay. In contrast, PNA+ B cells responded to murine (r)IL-5 or human B cell growth factor in the dextran sulfate (DxS) co-stimulator assay, to a much greater degree than did PNA- B cells. The same results were obtained with PNA+ and PNA- cells from LAF1 mice. Unfractionated LN B cells from nonimmunized SJL or BALB/c mice did not respond to IL-5 with or without DxS. B cell populations from BALB/c mice such as from spleen and peritoneal cavity, which are known to be high in Ly-1+B cells, responded to IL-5 alone, and more dramatically, to IL-5 as a co-stimulator with DxS. Such populations of cells from SJL mice, which are known to contain low numbers of Ly-1+B cells, responded markedly less. These results are consistent with those of others which show that in nonimmunized mice, Ly-1+B cells are a major IL-5 responsive subpopulation. IL-1 enhanced the proliferation of PNA+ cells in response to rIL-5 and had no effect on PNA- cells. IL-4 and IL-5 did not enhance each other's effects as co-stimulators of proliferation. In contrast to PNA+ B cells from immune LN, B cells activated by Escherichia coli endotoxin exhibited no responses to rIL-5. The present results indicate that in immune LN, PNA+, germinal center B cells constitute a prominent IL-5-responsive population. PMID- 2212648 TI - Augmentation of monocyte chemotaxis by 1 alpha,25-dihydroxyvitamin D3. Stimulation of defective migration of AIDS patients. AB - Preincubation for 20 h with 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) markedly augmented the chemotactic responsiveness of human blood monocytes to the classical chemoattractant, FMLP. A modest enhancement of monocyte spontaneous locomotion in the absence of chemoattractants was also observed. Maximal increase of monocyte migration was observed after pretreatment with 10(-9) M 1,25(OH)2D3 and was detectable at FMLP concentrations ranging from 10(-10) to 10(-7) M. Pretreatment with 1,25(OH)2D3 augmented the number of monocyte high affinity FMLP receptors (1500 +/- 220 and 3800 +/- 300 sites per cell for untreated and 1,25(OH)2D3-pretreated cells, respectively) with no significant changes in Kd values (2 +/- 0.5 nM and 4 +/- 1 nM, for untreated and 1,25(OH)2D3-pretreated monocytes). Enhanced chemotaxis was not restricted to FMLP, because 1,25(OH)2D3 treated monocytes showed enhanced migration also in response to activated C components and chemotactic cytokines. In agreement with previous observations, monocytes from AIDS patients showed defective migration capacity. In vitro exposure to 1,25(OH)2D3 stimulated monocyte migration in all 10 patients examined with considerable quantitative differences among individuals. Regulating the responsiveness of mature monocytes to chemo-attractants, 1,25(OH)2D3, produced systemically or in situ by immunocompetent cells, could play a role in the regulation of the recruitment of monocytes at sites of inflammation, cell mediated immunity, or bone resorption. The potential of 1,25(OH)2D3 as a restorative agent under conditions of defective phagocyte recruitment deserves further exploration. PMID- 2212649 TI - In vivo effects of anti-IL-4 monoclonal antibody on neonatal induction of tolerance and on an associated autoimmune syndrome. AB - The role of IL-4 in the cellular interactions leading to the induction of CTL tolerance to H-2b alloantigens and to the development of a lupus-like autoimmune disease in BALB/c mice after neonatal injection with (C57BL/6 x BALB/c)F1 cells was investigated in vivo by using an anti-IL-4 mAb. Treatment of F1 cell-injected BALB/c mice with 15 mg of anti-IL-4 mAb was shown to interfere with tolerance induction, as assessed by the high percentages of H-2b target cell lysis and the very low or undetectable levels of B cell chimerism markers observed in these mice. Treatment with 4.5 mg of anti-IL-4 mAb interfered with tolerance induction only in one-third of F1 cell-injected BALB/c mice, but that dose induces specific modulations of the autoimmune manifestations in all mice, leading to the nearly complete prevention of the disease. In particular, the production of anti-ssDNA IgG1 and of total IgG1 and IgE antibodies was seriously affected by the treatment, as well as the proliferation and membrane Ia and K expression of F1 donor splenic cells and thymic APC. Treatment of F1 cell-injected BALB/c mice between 24 and 48 h of life with 0.5 mg of anti-IL-4 mAb did not interfere with tolerance induction, but had similar effects on the autoimmune syndrome as treatment with 4.5 mg. These results suggest that, after F1 cell injection of newborn mice, IL-4 plays an important role in the cellular interactions leading to the induction of tolerance to the corresponding alloantigens and to the development of the associated autoimmune syndrome. PMID- 2212650 TI - Antagonistic and agonistic effects of transforming growth factor-beta and IL-1 in rheumatoid synovium. AB - We investigated potential mechanisms by which lymphocytes infiltrating rheumatoid synovium become immunosuppressed. In 20 of 22 synovial fluids and 12 of 13 synovial tissue culture supernatants, no IL-1 bioactivity could be detected in the thymocyte proliferation assay. These same preparations could, however, support proliferation of fibroblast monolayers, consistent with the presence of IL-1 and/or other fibroblast growth factors. Addition of either rheumatoid synovial fluids or synovial culture supernatants to exogenous IL-1 in the IL-1 bioassay caused marked inhibition of the assay indicative of an IL-1 inhibitor. This inhibition of IL-1 could be reversed by treating the effusions or supernatants with a neutralizing antibody to transforming growth factor-beta (TGF beta). Furthermore, monocyte-macrophages isolated from rheumatoid synovial fluid constitutively released both latent and active TGF-beta in culture at levels sufficient to completely block the biologic activity of 100 U/ml IL-1. The production of substantial levels of TGF-beta by synovial macrophages, as well as the apparent ability of these inflammatory macrophages to activate latent TGF beta, implicates TGF-beta not only as an important inhibitor of IL-1-induced lymphocyte proliferation, but also as a key cytokine in promoting synovial fibroblast hyperplasia and pathology. PMID- 2212651 TI - Participation of C1q and its receptor in adherence of human diploid fibroblast. AB - C1q binds through its collagen-like domain to specific surface receptors of fibroblasts and to adhesive elements of extracellular matrix including fibronectin, collagens, proteoglycans, and laminin. To determine whether C1q participates in fibroblast adhesion, cells in serum-free medium were plated on surfaces coated with purified C1q at physiologic ionic strength and pH. Surfaces coated with fibronectin or collagen type I served as positive controls, and those coated with BSA were negative controls. Substratum-adsorbed C1q promoted fibroblast adhesion to a maximum of 73% of available cells within 90 min at 37 degrees C. Adhesion was C1q concentration dependent, saturable, specific, and dependent on the collagen-like domain of the molecule. De novo protein synthesis plays a role in adhesion: pretreatment of fibroblasts with cycloheximide reduced adherence about 50% of controls. Addition of exogenous fibronectin, collagen type I, or C1q as soluble mediators did not affect adhesion of the cycloheximide treated cells to C1q substrate. Adhesion could be accounted for primarily, although not completely, by the C1q receptors. Antibodies raised against the Raji cell C1q receptors (alpha C1qR Ab) specifically inhibited fibroblast adhesion to C1q substrates about 60% of controls. The binding of fibroblasts to C1q substrates could be inhibited about 24% of controls with the GRGDTP cell recognition peptide. GRGDTP and alpha C1q Ab had an additive effect on adhesion that was inhibited 77 to 80% of controls. We conclude from these data that aggregated rather than monomeric C1q may be the natural ligand of the fibroblast C1q receptor, and the biologic function of the receptor in cells of the connective tissue may be cell adhesion. PMID- 2212652 TI - Self-binding antibodies (autobodies) form specific complexes in solution. AB - In this report we have shown that members of the murine self-binding antibody family, S107, form soluble complexes and precipitate under conditions in which non-self-binding antibodies remain in solution. Two approaches were used to demonstrate the self-association of autobodies: size-exclusion column chromatography and polyethylene glycol (PEG)-mediated precipitation assay. The anti-phosphorylcholine antibody T15 and two somatic variants, U4, which binds DNA, and U10, which has no identified specificity, produced larger precipitates in 10% PEG than other non-self-binding antibodies. The selectivity of PEG mediated precipitation of self-binding antibodies is demonstrated by reduction of precipitation with specific haptens known to inhibit self-binding in solid-phase assays. Phosphorylcholine and nucleotides reduced precipitation of T15 and U4, respectively, but not U10. To rule out Fc-Fc mediated self-association in solution, we have also demonstrated self-complexing of F(ab')2 fragments of T15 using PEG. The self-binding locus was further dissected using peptides derived from V regions. A 24-residue peptide derived from the second hypervariable region of the VH of S107 specifically enhanced precipitation of T15, U4, and U10, but not other antibodies. These results provide evidence of a dormant potential of self-binding antibodies to precipitate under conditions that reduce the solubility of proteins. The implication of this potential is discussed with respect to pathological complex formation. PMID- 2212653 TI - Inhibition of protein kinase C by a peptide conjugate homologous to a domain of the retroviral protein p15E. AB - Retroviral infection is associated with immunosuppression, which has been shown to be due, in part, to the action of the envelope protein p15E. We studied a synthetic peptide (CKS-17) homologous to a highly conserved domain of the retroviral envelope protein p15E, which, when conjugated to BSA (CKS-17-BSA), can inhibit IL-1- and phorbol ester-mediated responses in cultured murine thymoma cells, and Ca2(+)- and phosphatidylserine-dependent protein kinase C (PKC) activity of cell homogenates. We characterized the mechanism of inhibition of PKC by the peptide. Using PKC purified from rat brain we found that CKS-17-BSA inhibited PKC-catalyzed Ca2(+)- and phosphatidylserine-dependent histone phosphorylation with an estimated ID50 of 4 microM. CKS-17-BSA did not inhibit the catalytic subunit of cAMP-dependent protein kinase. CKS-17-BSA also inhibited the Ca2(+)- and PS-independent activity of a catalytic fragment of PKC that was generated by limited trypsin treatment. However, CKS-17-BSA did not act as a competitive inhibitor of PKC with respect to ATP or phosphoacceptor substrate, despite the similarity between the CKS-17 sequence and substrates and pseudosubstrates of PKC. We conclude that this peptide homologue of a retroviral envelope protein has a novel mechanism of inhibition of PKC. PMID- 2212654 TI - Analysis of the primary signals required for activation of the mitogenic pathway in murine thymocytes from protein phosphorylation patterns. AB - It has been proposed that phorbol esters and the Ca2+ ionophore A23187 are effective comitogens for some species of lymphocytes because together they mimic the normal secondary signals for cell activation by mitogens that cause phosphatidylinositol 4,5-bisphosphate (PtdInsP2) breakdown (e.g., anti-TCR and anti-Thy-1 antibodies and Con A). To test whether activation of protein kinase C and an increase in [Ca2+]i account for the activation of the mitogenic pathway in murine thymocytes by the mitogens that cause PtdInsP2 breakdown, the two dimensional phosphorylation patterns generated by the three classes of mitogens (protein kinase C activator, Ca2+ ionophore, and activator of PtdInsP2 breakdown) and by activators of cAMP-dependent kinases have been compared. From the phosphorylation patterns, by which each mitogen could be distinguished reproducibly, it was concluded that: 1) The phosphorylation patterns generated by the mitogens that activate PtdInsP2 breakdown are only slightly affected by the removal of extracellular Ca2+ under conditions that abolish the normal rise in [Ca2+]i and do not therefore depend on the activation of Ca2(+)-dependent protein kinases. In contrast, the phosphorylation pattern generated by A23187 is totally dependent on extracellular Ca2+. 2) Neither A23187 nor the mitogens that activate PtdInsP2 breakdown nor activators of cAMP-dependent kinases caused significant activation of protein kinase C assayed by phosphorylation of the diagnostic proteins 80b and 78a. Consistent with this conclusion, only the phorbol esters or oleoyl acyl glycerol caused translocation of protein kinase C activity from the cytosolic to the membrane fraction. 3) Neither A23187 nor the mitogens that cause PtdInsP2 breakdown activated cAMP-dependent kinases. Taken together the data imply that the mitogens that cause PtdInsP2 breakdown must generate an additional, independent primary mitogenic signal. It is suggested that this signal may be the activation of tyrosine kinases (e.g., p56lck) via the TCR and working hypotheses for effective combinations of primary mitogenic signals that will activate DNA synthesis are developed. PMID- 2212655 TI - Platelet-activating factor enhances Ig production in B lymphoblastoid cell lines. AB - Platelet-activating factor (PAF) is a highly potent phospholipid mediator known to be active in many biologic systems. To date, little is known of the effect of PAF on B lymphocytes. Using two Ig-secreting B lymphoblastoid cell lines, we have demonstrated that PAF can enhance Ig production by these cells in a dose dependent fashion. PAF also causes significant alteration of the kinetics of Ig secretion in these lymphoblastoid cell lines. The effect of PAF is rapid, with detection of 6- to 12-fold increases in Ig production in the first 24 h of cell culture, followed by a plateau during the next 24 to 48 h. The specificity of the PAF effect on Ig secretion is emphasized by lyso-PAF having no Ig-enhancing properties and by the inhibition of Ig enhancement in the presence of the structural analogue PAF antagonist CV3988 and the soluble nonstructural analogue PAF receptor antagonist Web 2086. PAF does not cause an increase in the kinetics of cell proliferation or an increase in cell numbers at any time during a 72-h culture period. In an attempt to explain the increase in Ig secretion in the absence of changes in growth parameters, an ELISA spot assay for enumeration of Ig-secreting cells was developed. This assay demonstrated that the increase in Ig production is likely due to enhancement of single cell Ig secretion rather than an increase in cell number. These data indicate that PAF may have an important immunomodulatory role in the production of Ig by B lymphocytes. PMID- 2212656 TI - Identification of a cathepsin G-like proteinase in the MCTC type of human mast cell. AB - Human mast cells can be divided into two subsets based on serine proteinase composition: a subset that contains the serine proteinases tryptase and chymase (MCTC), and a subset that contains only tryptase (MCT). In this study we examined both types of mast cells for two additional proteinases, cathepsin G and elastase, which are the major serine proteinases of neutrophils. Because human mast cell chymase and cathepsin G are both chymotrypsin-like proteinases, the properties of these enzymes were further defined to confirm their distinctiveness. Comparison of their N-terminal sequences showed 30% nonidentity over the first 35 amino acids, and comparison of their amino acid compositions demonstrated a marked difference in their Arg/Lys ratios, which was approximately 1 for chymase and 10 for cathepsin G. Endoglycosidase F treatment increased the electrophoretic mobility of chymase on SDS gels, indicating significant N-linked carbohydrate on chymase; no effect was observed on cathepsin G. Immunoprecipitation and immunoblotting with specific antisera to each proteinase revealed little, if any, detectable cross-reactivity. Immunocytochemical studies showed selective labelling of MCTC type mast cells by cathepsin G antiserum in sections of human skin, lung, and bowel. No labeling of mast cells by elastase antiserum was detected in the same tissues, or in dispersed mast cells from lung and skin. A protein cross-reactive with cathepsin G was identified in extracts of human skin mast cells by immunoblot analysis. This protein had a slightly higher Mr (30,000) than the predominant form of neutrophil cathepsin G (Mr 28,000), and could not be separated from chymase (Mr 30,000) by SDS gel electrophoresis because of the size similarity. Using casein, a protein substrate hydrolyzed at comparable rates by chymase and cathepsin G, it was shown that about 30% of the caseinolytic activity in mast cell extracts was sensitive to inhibitors of cathepsin G that had no effect on chymase. Hydrolytic activity characteristic of elastase was not detected in these extracts. These studies indicate that human MCTC mast cells may contain two different chymotrypsin-like proteinases: chymase and a proteinase more closely related to cathepsin G, both of which are undetectable in MCT mast cells. Neutrophil elastase, on the other hand, was not detected in human mast cells by our procedures. PMID- 2212657 TI - Synthetic peptide immunogens eliciting antibodies to Plasmodium falciparum sporozoite and merozoite surface antigens in H-2b and H-2k mice. AB - Peptides representing conserved (MSA2/1A and MSA2/1B) and variant (MSA2/2, MSA2/6 and MSA2/7) regions of the merozoite surface Ag 2 (MSA2) of Plasmodium falciparum (FCQ-27/PNG isolate) were coupled to either peptide NP(NANP)5NA or peptide C(NANP)6 both of which contained the core sequence (NANP)n. The coupling was done via the N-terminus of one peptide and a cysteine residue on either terminus of the other. BL/10 (H-2b) and B10.BR (H-2k) mice were immunized with these MSA2 (NANP)n conjugates. The mice were also immunized with the unconjugated MSA2 peptides and with NP(NANP)5NA and C(NANP)6. Antibody responses were evaluated by 1) ELISA, in which the MSA2 peptides and C(NANP)6 were used as Ag; 2) immunofluorescence assays (IFAT) against intact sporozoites and merozoites; and 3) immunoblotting experiments against solubilized P. falciparum blood stage proteins. High titer antibodies to (NANP)n were elicited in both BL/10 and B10.BR mice after immunization with all the conjugates except MSA2/7-(NANP)n which gave only a very limited response in B10.BR mice. These antibodies recognized unfixed sporozoites. The conjugates also elicited antibodies to MSA2 as shown by ELISA, IFAT, and immunoblotting except for mice immunized with MSA2/1B-(NANP)n where an anti-MSA2 response was only detectable by immunoblotting. Immunization with unconjugated MSA2 peptides showed that MSA2/2 was immunogenic in both BL/10 and BR.10 mice, with MSA2/6 and MSA2/7 being immunogenic only in BL/10 mice. The antibodies elicited recognized both merozoites and the MSA2 protein. However, the antibody titers were lower overall than those seen when these peptides were used in the conjugated form. No anti-MSA2 antibodies were detected after immunization with MSA2/1A and MSA2/1B. Immunization of mice with the peptide NP(NANP)5NA produced antibodies in BL/10 (H-2b) mice only, and the immunogenicity of this preparation was poor. In contrast, C(NANP)6 produced a strong antibody response in both mouse strains. The antibodies elicited by NP(NANP)5NA and C(NANP)6 recognised sporozoites in IFAT. The MSA2 peptides studied (or their derivatives) were previously shown to be recognized by human T cells. Their immunogenic potential shows promise in that complex anti-P. falciparum responses can be elicited with simple synthetic immunogens based on these peptides. PMID- 2212658 TI - Rapid nonlysosomal degradation of assembled HLA class II glycoproteins incorporating a mutant DR alpha-chain. AB - Gamma irradiation followed by antibody and complement selection was used to isolate a human B-lymphoblastoid cell line that no longer expresses HLA-DR molecules on its cell surface. Cell surface expression in the mutant (HMy2.DRN) was restored by transfecting a wildtype DRA but not a DRB cDNA, suggesting that a structural mutation in the DRA mRNA or protein was responsible for the lack of cell surface expression. Nucleotide sequence analysis of the DRA mRNA from HMy2.DRN revealed a 75 nucleotide deletion corresponding to the start of the alpha 2 domain and involving one of two cysteines that are involved in the formation of an intrachain disulfide bond. At the biochemical level, only minute quantities of HLA-DR could be precipitated from this cell line after a 4-h continuous label with 35S-methionine. HLA-DR beta and the class II-associated invariant chain could be seen coprecipitating with the mutant DR alpha-chain, suggesting a limited accumulation of normally assembled molecules. However, by carrying out the labeling at 16 degrees C instead of 37 degrees C, equivalent amounts of HLA-DR could be precipitated from parent and mutant alike. The mutant DR alpha chain was found in association with the beta-chain, but with reduced association with the invariant chain under these conditions. Pulse chase analysis in the parent and mutant cell lines indicated that this mutant DR alpha beta I complex undergoes a process of degradation at 37 degrees C. Inhibitors of intracellular transport such as monensin were ineffective in blocking this process of degradation. This work is consistent with published reports implicating the involvement of a pre-Golgi or an early Golgi compartment in the proteolysis of aberrantly folded or assembled multisubunit proteins. PMID- 2212659 TI - Sequence and chromosomal location of the I-309 gene. Relationship to genes encoding a family of inflammatory cytokines. AB - We previously reported the isolation and characterization of a cDNA clone, I-309, that encodes a small secreted protein produced by activated human T lymphocytes. This protein is structurally related to a large number of recently identified proteins that are secreted upon cellular activation. In this report we describe the isolation and characterization of the gene encoding I-309. The genomic organization is essentially identical to that found in the genes encoding the structurally similar proteins TCA-3, hJE/MCP-1, and mJE, strengthening the hypothesis that these genes are evolutionarily related. The region of the I-309 gene 5' of the mRNA cap site exhibits extensive nucleotide sequence homology with the same region of the murine gene TCA-3, providing additional evidence that I 309 and TCA-3 are likely to be homologs. Finally, panels of rodent-human somatic cell hybrids were used to map the I-309 gene to human chromosome 17. In conjunction with recent mapping data from other laboratories, this result suggests the presence of a cluster of related genes on this chromosome. PMID- 2212660 TI - Expression and characterization of TCA3: a murine inflammatory protein. AB - TCA3 is a cDNA originally isolated from activated T cells. Transcription of this gene has been shown to correlate with Ag-induced cellular activation of both T cells and mast cells. Based on the predicted amino acid sequence encoded by the cDNA, we previously proposed that TCA3 represents a cytokine. In this report we have used rDNA technology to express TCA3 in two mammalian cell lines. In both cases, TCA3 was expressed as a secreted molecule with an apparent molecular mass of 16 kDa. Digestion of the (rTCA3) with the enzyme N-glycanase revealed that approximately 8 kDa is caused by N-linked glycosylation. Intradermal injection of rTCA3 into mouse footpads resulted in a rapid swelling response. The sites of injection were characterized histologically by a local accumulation of neutrophils. These findings are discussed with particular attention to a family of related proteins, some of whose members also have inflammatory properties. PMID- 2212661 TI - IL-2-PE40 prevents the development of tumors in mice injected with IL-2 receptor expressing EL4 transfectant tumor cells. AB - A number of different immunotherapeutic reagents are currently being developed to target IL-2R for the treatment of leukemia, graft rejection, and certain autoimmune diseases. Previously, we have shown that IL-2-PE40, a chimeric protein composed of human IL-2 linked to the N-terminus of a truncated form of Pseudomonas exotoxin (PE), could effectively kill a variety of cell lines in vitro expressing either low, intermediate, or high affinity IL-2R. Here, we demonstrate that IL-2-PE40 can successfully retard or prevent the growth of a lethal ascites tumor or a solid tumor composed of EL4J murine thymoma cells transfected with the p55 murine IL-2R. The transfected line, EL4J-3.4, expresses 1,000 to 3,000 high affinity IL-2R. Survival extension in the ascites model was achieved by initiating treatment either after 4 to 6 h or within 5 days post tumor injection in both athymic nude and C57BL/6 mice. Similarly, the growth of an aggressive s.c. solid tumor could also be inhibited. Extension of survival was not achieved either by using the truncated toxin alone not attached to IL-2 or by using an IL-2-PE40Asp553 mutant lacking a functional toxin. Survival extension was not caused by IL-2 activated NK or other host effector mechanisms as IL-2 PE40 was unable to prevent the receptor-negative EL4J parental line from forming a lethal ascites or a solid tumor. Thus, IL-2-PE40 is a potent, specific cytolytic reagent that may prove useful in the arsenal of anti-IL-2R immunotherapeutics. PMID- 2212662 TI - Capsular polysaccharide of Haemophilus influenzae type b (Hib PS) is a mitogen for murine B cells. PMID- 2212663 TI - Focusing: the dilemma of interpreting sharp images on a blurred background. PMID- 2212664 TI - Freshly isolated spleen dendritic cells and epidermal Langerhans cells undergo similar phenotypic and functional changes during short-term culture. AB - Spleen dendritic cells (DC) and epidermal Langerhans cells (LC) belong to the same family of dendritic leukocytes and are considered to be prototypes of lymphoid DC and nonlymphoid DC, respectively. These cells are active APC in vitro and play a key role in the induction of primary T cell dependent immune responses in vivo. Two functional states of LC have been characterized in vitro, freshly isolated LC and cultured LC (cLC). That cLC closely resemble spleen DC in phenotype and function, has led to the hypothesis that LC undergo maturation toward DC while in culture, an event that has been correlated with the emigration of LC from skin into lymphoid organs. To date, however, DC have been studied only after overnight culture. To better understand the relationship between LC and DC, we examined DC shortly after their isolation from spleen, and after 24 h of culture. Freshly isolated DC (fDC) express high levels of MHC molecules and low levels of Fc gamma RII and C3biR; fDC also uniformly express the Ag recognized by the mAb 33D1, NLDC-145, and J11d. After culture, DC display a marked increase in the expression of MHC molecules, and they are induced to express the low affinity receptor for IL-2. By contrast, the expression of Fc gamma RII and F4/80 decreases with culture. With respect to function, fDC can efficiently present keyhole limpet hemocyanin to Ag-specific T cells, whereas cultured DC exhibit a marked reduction in this capacity. Finally, both fDC and cultured DC are capable of endocytosing surface Ia molecules, but only fDC are able to deliver them into acidic compartments. Our data indicate that fDC from spleen resemble freshly isolated LC from epidermis and that both cells undergo parallel changes during culture. These results suggest that LC and DC possess analogous attributes in vivo and respond similarly to external influences. PMID- 2212665 TI - Evidence that cutaneous antigen-presenting cells migrate to regional lymph nodes during contact sensitization. AB - These studies address the hypothesis that Ag-bearing epidermal Langerhans cells migrate to the regional lymph node during contact sensitization and function as APC. Skin from C3H mice was grafted onto BALB/c nude mice, and 7 or 14 days later, the recipients were sensitized with FITC through the grafts. APC from lymph nodes draining the site of sensitization were capable of sensitizing C3H recipients to FITC. Because sensitization is MHC restricted, only cells reaching the lymph node from the grafted skin could have induced contact hypersensitivity in C3H mice. Examination of the FITC+ draining lymph node cells by immunofluorescence and immunoelectron microscopy demonstrated that all were Ia+, most were F4/80+, and some contained Birbeck granules. These studies demonstrate that Ia+, FITC+ cells from the skin, at least some of which are Langerhans cells, leave the skin after epicutaneous sensitization with FITC and participate in the initiation of the contact hypersensitivity response within the regional lymph node. PMID- 2212666 TI - Human severe combined immunodeficiency disease: phenotypic and functional characteristics of peripheral B lymphocytes. AB - Human severe combined immunodeficiency disease (SCID) includes an X-chromosome linked type characterized by a complete absence of mature T cells, hypogammaglobulinemia but normal or elevated number of B cells, suggesting that the disease results from a block in early T cell differentiation. It has been shown that B cells from obligate carrier women of this disorder exhibit the preferential use of the nonmutant X chromosome as the active X (as shown for T cells), suggesting that the SCID gene product has a direct effect on B cells as well as on T cells. To examine this question, we analyzed the phenotypic and functional characteristics of peripheral B cells from nine infants with SCID. We found a constant absence of spontaneously expressed activation Ag on B cell membrane from all SCID patients tested which contrasts with the phenotypic pattern exhibited by age-matched infants whom all cells bearing surface Ig express the 4F2 Ag and to a lesser extent the transferrin receptor. Concurrently, B cells from SCID patients have a profound impairment in their responses to stimuli that induce in vitro B cell proliferation and differentiation. Although rIL-2 and low-Mr B cell growth factor are potent inducers of proliferation on age matched infants' B cells, they are poorly efficient in inducing proliferation of anti-mu-activated SCID B cells. This impairment is not related to the resting B cell phenotype of SCID B cells as shown by comparison with normal resting B cells. Furthermore, we observed an apparent block in B cell differentiation inasmuch as neither rIL-2 nor rIL-6 could support SAC-activated SCID B cell differentiation, both lymphokines being very efficient in inducing SAC-activated age-matched infants' B cell or purified resting B cell differentiation. These results suggest that the SCID gene defect has a direct effect on B cells and is required during B cell maturation. PMID- 2212667 TI - Cytokine regulation of IL-1 beta gene expression in the human polymorphonuclear leukocyte. AB - Although recently polymorphonuclear leukocytes (PMN) have been identified as producers of IL-1 beta in response to LPS and granulocyte/monocyte colony stimulating factor, little is known regarding the ability of other cytokines to induce the production of IL-1 beta in the PMN. Inasmuch as IL-1 and TNF have been shown to be important priming agents, as well as agents that induce migration of PMN, we investigated their effect on IL-1 beta gene expression in human peripheral blood PMN. In the present study, we demonstrate that human peripheral blood PMN produce IL-1 beta in response to IL-1 alpha, IL-1 beta, and TNF-alpha. Control (unstimulated) human PMN had virtually undetectable levels of IL-1 beta mRNA. Either IL-1 beta or TNF, induced PMN to transiently express IL-1 beta mRNA with peak expression at 1 h, returning to untreated levels by 2 h. A dose response indicated that as little as 0.05 ng/ml of IL-1 beta or TNF resulted in IL-1 beta induction, with maximal effects at 1 ng/ml of IL-1 beta and 5 ng/ml of TNF. IL-1 alpha or IL-1 beta exhibited similar dose responses in IL-1 beta mRNA induction. Inasmuch as cytokines have been shown to have synergistic effects in cell function studies, we induced PMN with a combination of maximally effective doses of TNF plus IL-1 beta. They demonstrated a cooperative effect on IL-1 beta gene expression, in that mRNA levels were sustained for three hours. IL-1 beta Ag expression, as measured by ELISA, paralleled IL-1 beta mRNA expression with cell associated peak levels at 2 to 4 h. IL-1 beta Ag levels in PMN lysates and supernatants correlated with IL-1 beta mRNA levels, i.e., TNF + IL-1 greater than TNF greater than IL-1. Thus, these studies represent the first demonstration of IL-1 and TNF induction of IL-1 beta gene expression in the PMN. Furthermore, the time course of induction is unique to the PMN, with peak induction of mRNA at 1 h, which is consistent with the short lived nature of these cells in inflammatory lesions. PMID- 2212668 TI - Expression of the human IL-2 receptor on lymphocytes involves rapid turnover of its p55 alpha-subunit (Tac). AB - Upon mitogenic stimulation, both mRNA encoding the p55 alpha-subunit (Tac) of the human IL-2R alpha and IL-2R alpha protein are induced and expressed in tonsil lymphocyte populations over several days. Using a quantitative dot-blot immunoassay for the IL-2R alpha subunit, a rapid disappearance of this polypeptide from cells is demonstrated in the presence of the translation inhibitor, cycloheximide. The half-life of IL-2R alpha subunit protein is 2 to 3 h. This decline in cell-associated IL-2R alpha subunit is matched by a rapid decline in IL-2R alpha on the cell surface and is not accompanied by any increase in soluble IL-2R alpha protein. Long term expression of the IL-2R on the cell surface is thus the result of continual synthesis and rapid breakdown of IL-2R alpha chains in the cell. Steady state expression of the IL-2R after an immune stimulus hence depends upon continuous expression of the IL-2R alpha subunit gene. Rapid turnover of the unstable alpha-subunit on the cell surface provides a novel mechanism for sensitive control of functional IL-2R expression. PMID- 2212669 TI - The lymphocyte-specific protein LSP1 is associated with the cytoskeleton and co caps with membrane IgM. AB - LSP1 is a lymphocyte-specific intracellular Ca2(+)-binding protein. We found previously that a fraction of the total cellular pool of LSP1 protein accumulates at or near the cytoplasmic face of the plasma membrane. LSP1 protein was also shown to be present in the cytoplasm. Here we report that approximately 10% of the total intracellular LSP1 protein is associated with the Nonidet P-40 insoluble cytoskeleton of the mIgM+, mIgD+ B lymphoma cell line BAL17. Variation in conditions of extraction did not alter this value. To rule out the possibility that LSP1 associates with the nucleus that is also present in the detergent insoluble pellet, we prepared a separate nuclear fraction essentially free of cytoskeletal material and found only trace amounts of LSP1 protein. After accounting for yield losses during subcellular fractionation by measuring the recovery of 125I-labeled membrane IgM, or of the cytoplasmic marker enzyme lactate dehydrogenase activity, the LSP1 in membrane fractions was calculated to represent approximately 30% of the total cellular LSP1 and cytoplasmic LSP1 accounted for approximately 55% of the total. Approximately 75% of the plasma membrane LSP1 protein was soluble in 1% Nonidet P-40 containing buffer, indicating that the majority of the LSP1 in the plasma membrane fraction was distinct from the cytoskeletal LSP1 protein. The preparation of membrane fractions in the presence of 1 M NaCl, or washing of membranes in 3 M KCl did not diminish the levels of membrane LSP1. These results show the existence of three discrete intracellular LSP1 pools. Double label immunofluorescence studies showed that the peripheral ring-like distribution of LSP1 in BAL17 cells became a distinct cap upon cross-linking the mIgM. These intracellular LSP1 caps were always found to be located directly underneath the mIgM caps. PMID- 2212670 TI - Platelet C1q receptor interactions with collagen- and C1q-coated surfaces. AB - We recently described specific binding sites for C1q on human blood platelets. Structural similarities between the amino-terminal of C1q and collagen have suggested that receptors for both molecules on platelets might be the same. The present study thus compared the interaction of purified C1q receptors (C1qR) and whole platelets with collagen- and C1q-coated polystyrene surfaces. Surfaces coated with BSA or gelatin served as controls. Purified 125I-labeled C1qR recognized both C1q- and collagen-coated surfaces in a divalent, cation independent manner. This adhesion was inhibited by polyclonal or monoclonal (II1/D1) anti-C1qR antibodies. Although C1qR adhered preferentially to C1q-coated surfaces, adhesion to bovine and human type I collagen, as well as to human type III and V collagen, was also noted. In parallel studies, 51Cr-labeled platelets bound equally well to collagen- or C1q-coated surfaces, albeit in a magnesium dependent manner. Partial inhibition of platelet adhesion was observed in the presence of RGDS, despite the inability of RGDS to modify C1qR interaction with C1q or collagen. Moreover, anti C1qR antibodies selectively inhibited platelet adhesion to C1q-coated surfaces, whereas antibodies specific for the GPIa/IIa collagen receptor (6F1) preferentially inhibited platelet collagen interactions. These data support the presence of distinct platelet membrane C1qR, which may cross-react with collagen, and suggest that C1qR are necessary but not sufficient for platelet adhesion to C1q-coated surfaces. Additional divalent cation and/or RGD-sensitive binding sites may participate. PMID- 2212671 TI - Analysis of the immune response to lipopolysaccharide. Existence of an interspecies cross-reactive idiotype associated with anti-lipid A antibodies. AB - LPS is the major surface glycolipid on gram-negative bacteria. In this work, we have idiotypically characterized the antibody response against LPS in different species. To do this, we have produced mAb against LPS. Binding of many of these antibodies to LPS could be inhibited by LPS and lipid A, indicating that the monoclonals are specific for lipid A, the toxic moiety of the LPS molecule. One anti-lipid A antibody, IC9, proved protective against gram-negative bacteremia and endotoxic shock in murine protection models. We generated anti-idiotypic antibodies against IC9. The binding of several of these anti-Id to IC9 was specifically inhibited by lipid A. We used these anti-Id to characterize the anti LPS response, and the results revealed that the IC9 Id is conserved in different species. The importance of an interspecies cross-reactive Id in the response to endotoxin and its relevance in vaccine development for septic shock are discussed. PMID- 2212672 TI - Endothelial and leukocyte forms of IL-8. Conversion by thrombin and interactions with neutrophils. AB - We have recently shown that endothelial cell-derived IL-8 inhibits neutrophil adhesion to IL1-beta-activated human umbilical vein endothelial cell monolayers. IL-8 secreted by T lymphocytes or monocytes has been characterized as a promoter of neutrophil degranulation and chemotaxis. The IL-8 isolated from each of these cell types is a mixture of two IL-8 polypeptides, one consisting of 72 amino acids (herein called [ser-IL-8]72) and the other 77 amino acids (an N-terminal extended form herein called [ala-IL-8]77). IL-8 derived from T lymphocytes and monocytes is predominantly [ser-IL-8]72, whereas endothelial-derived IL-8 is highly enriched (greater than 80%) in [ala-IL-8]77. We address the relationship and activities of these two forms of IL-8 using recombinant proteins expressed by both mammalian cells and Escherichia coli. Thrombin was found to efficiently convert [ala-IL-8]77 to [ser-IL-8]72. In contrast, urokinase and tissue-type plasminogen activator were unable to cleave [ala-IL-8]77, and trypsin generated multiple IL-8 cleavage fragments. In competitive binding assays using 125I[ala-IL 8]77 neutrophils exhibited a twofold preference for [ser-IL-8]72 over [ala-IL 8]77. Both forms of IL-8 inhibited neutrophil adhesion to IL-1-beta-activated HUVEC monolayers by up to 90%. However, [ser-IL-8]72 was approximately 10-fold more potent than [ala-IL-8]77 in these assays (ED50 approximately 0.3 nM for [ser IL-8]72 vs approximately 3 nM for [ala-IL-8]77. Both forms of IL-8 promoted degranulation of cytochalasin B-treated neutrophils [[ser-IL-8]72 (ED50 greater than 10 nM) was two- to three-fold more potent than [ala-IL-8]77], although in this regard they were less active than FMLP. Our data suggest that [ala-IL-8]77 and [ser-IL-8]72 have qualitatively similar and potentially complex biological activities, and that full activation of IL-8 requires cleavage to the [ser-IL 8]72 form. In the case of inflamed endothelial cells this activation could be mediated by thrombin generated in the procoagulant environment associated with these cells. PMID- 2212673 TI - The subcellular distribution of platelet-activating factor in stimulated human neutrophils. AB - Exposure of human peripheral blood neutrophils to a variety of phagocytic and soluble stimuli is known to induce the synthesis and secretion of platelet activating factor (PAF), a unique ether-linked phospholipid. It has recently been observed in this laboratory, that whereas some PAF is secreted to the exterior of the cell, the majority of the newly synthesized PAF is retained intracellularly. This observation led us to investigate the subcellular distribution of intracellular PAF in stimulated human neutrophils, and to question the possible intracellular role of this molecule. Approximately 2 x 10(8) neutrophils were exposed to either the phagocytic stimulus, opsonized zymosan particles (25 particles/cell), the soluble stimulus, Ca2(+)-ionophore A23187 (5 micrograms/ml), or were left unstimulated for up to 30 min. After disruption, the cells were fractionated into nuclei, phagolysosomes, specific granules, azurophil granules, membranes, and cytosol. Fractions were analyzed for representative organellar markers, as well as for total protein, total phospholipid phosphorous, and PAF. In cells that had been exposed to opsonized zymosan particles, the majority of the PAF was localized to the phagolysosomal fraction, with lesser amounts being detected in the membranous and granular fractions of the cells. In neutrophils that had been exposed to A23187, the major portion of the PAF was detected in the membranous fractions with smaller amounts being seen in fractions corresponding to the specific granules. On the basis of these data, combined with the known physicochemical properties of PAF, it is speculated that the PAF detected at discrete intracellular locations in stimulated human neutrophils may play an important role in the endocytic and/or secretory functions of neutrophils. PMID- 2212674 TI - Cell specificity of granzyme gene expression. AB - Granzymes are serine proteases present in secretory granules of cytolytic T lymphocyte lines. We have studied the expression of the granzyme family (granzyme A, B, C, D, E, F, and G) in different lymphoid cell populations and cell lines as well as in nonlymphoid cells and tissues. Our data show that with few exceptions expression of granzyme genes is restricted to T cells and their thymic precursors. In mature T cells granzymes are expressed only upon activation. The same is true for thymocytes, with the exception of grazyme A that is expressed also in non-stimulated cells. In T cells and thymocytes the distribution of mRNAs coding for different granzymes depends on the subpopulation tested and the activation protocol. Highly cytolytic PEL express granzymes A and B but none of the other granzymes. PMID- 2212675 TI - Two divergent routes of evolution gave rise to the DRw13 haplotypes. AB - The HLA class II genes and haplotypes have evolved over a long period of evolutionary time by mechanisms such as gene conversion, reciprocal recombination and point mutation. The extent of the diversity generated is most clearly evident in an analysis of the HLA class II alleles present within DRw13 haplotypes. This study uses cDNA sequencing to examine the first domains of DRB1, DRB3, DQA1, and DQB1 alleles from several American black individuals expressing seven different DRw13 haplotypes, five with undefined HLA-D specificities (i.e., not Dw18 or Dw19). Two new DRw13 alleles described in this study are the first examples of convergent evolution of DR alleles in which gene conversion has apparently combined segments of DRB1 alleles encoding DRw11 and DRw8 to generate two new DRB1 alleles, DRB1*1303 and DRB1*1304, that encode molecules bearing serologic determinants of a third allele, DRw13. These new DRw13 alleles are found embedded in haplotypes of DRw11 origin distinct from haplotypes encoding previously identified DRw13 alleles, DRB1*1301 and DRB1*1302. These data suggest that two evolutionary pathways may have given rise to two subgroups of alleles encoding molecules that share DRw13 serologic determinants yet which possess different structural and, likely, functional motifs. Reciprocal gene recombination events resulting in different DR, DRw52 and DQ allele combinations also appear to have played a crucial role in augmenting the level of diversity found in DRw13 haplotypes. Recombination has resulted in the association of one of the new DRw13 alleles with a DQw2 allele normally found associated with DR7 and the association of the DRw52c-associated DRw13 allele (DRB1*1302) with three different DQw1 alleles. The seven DRw13 haplotypes that have resulted from the effect of recombination on haplotypes formed by the two pathways of DRw13 allelic diversification have resulted in different repertoires of class II molecules and, most likely, different immune response profiles in individuals with these haplotypes. PMID- 2212676 TI - Regulation of HLA class II molecule expressions by IFN-gamma. The signal transduction mechanism in glioblastoma cell lines. AB - We examined the signal transduction mechanism responsible for the IFN-gamma induced HLA class II molecule expressions on glioblastoma cell lines, T98G and A172. A series of experiments demonstrated that the activation of protein kinase C (PKC) is involved in the DR and DP molecule expressions on T98G cells. In addition to the activation of PKC, calcium influx appeared to be involved in the DR and DP molecule expressions on T98G. Northern blot analyses with actinomycin D or cycloheximide revealed that these second messengers induce the transcription of DRA and B and DPA and B genes without de novo protein synthesis. Furthermore, we examined the region of the DPB gene that is responsible for IFN-gamma-induced gene transcription by gene transfer of a series of 5' and 3' deletion mutants in which the upstream region of the DPB was linked to a reporter gene, chloramphenicol acetyltransferase. By using these deletion mutants, it appeared that the region between -152 and -126 bp contains a critical IFN-gamma-responsive element. Taken together, these results suggest that IFN-gamma activates PKC and stimulates calcium influx, resulting in the induction of transcription of DRA and B and DPA and B genes without de novo protein synthesis. In DPB gene, we speculate that preexiting protein(s) phosphorylated by PKC in the presence of Ca2+ might directly bind or indirectly interact with the region between -152 and 126 bp of the upstream sequence, leading to the induction of the transcription (possibly in concert with other nuclear protein(s) bound to the promoter sequences). PMID- 2212677 TI - Low doses of IL-4 injected perilymphatically in tumor-bearing mice inhibit the growth of poorly and apparently nonimmunogenic tumors and induce a tumor-specific immune memory. AB - The ability of rIL-4 to trigger host reactivity against both a chemically induced fibrosarcoma (CE-2) and a spontaneous adenocarcinoma (TS/A) of BALB/c mice was studied. Daily local s.c. administration around tumor draining lymph nodes of 10 injections of progressive amounts (0.00001 to 1000 pg/day) of rIL-4 induced appreciable inhibition of the growth of both tumors after a dose-response survival curve peaking at 0.1 pg/day. Inasmuch as rIL-4 has no direct antitumor activity, as shown by in vitro tests, host immune reactivity plays a fundamental role in this lymphokine activated tumor inhibition (LATI). LATI, in fact, is abolished when recipient mice are sublethally irradiated or treated with cyclosporin A, or when the reactivity of CD4+ lymphocytes is suppressed, whereas it is not affected by anti-asialo GM1 antibody. The morphologic data show that rIL-4 LATI rests on the recruitment of several cell reaction mechanisms, among which those that are nonspecific seem to predominate. rIL-4 LATI also leads to a state of long lasting and specific immune memory: the growth of a second contralateral tumor challenge is significantly impaired after LATI. This immune memory takes place after LATI of both the poorly immunogenic CE-2 fibrosarcoma and the TS/A adenocarcinoma, previously classed as nonimmunogenic on the basis of immunization-protection tests. In the latter case, adoptive transfer experiments show that Thy-1+ lymphocytes and, in particular, the CD4 cell-depleted T lymphocyte subpopulation, are responsible for the immune memory. Finally, the ability of rIL-4 to trigger LATI is greater than that of the most effective doses of rIL-2, rIL-1 beta, and IFN-gamma, whereas its association with rIL-1 beta induces a more effective immune memory. PMID- 2212678 TI - Evaluation of the efficiency of two IgA immune complex assays. AB - Two IgA immune complex assays, namely the anti-IgA inhibition of binding assay (a IgA-InhBA) and the IgA polyethylene glycol assay (IgA-PEG assay) were evaluated using IgA aggregates (AIgA) of well defined sizes. AIgA was prepared by heat treatment. After ultracentrifugation the size of AIgA was found to be in a range between 7 S and 64 S. Five AIgA pools (greater than 64 S, 44-64 S, 24-43 S, 20-24 S and 9-19 S) and a pool of monomeric IgA were prepared to test the efficiency of the two assays. The IgA-PEG assay exclusively detected very large sized AIgA (greater than 64 S), whereas the a-IgA-InhBA detected also AIgA of intermediate size (9-19 S). The sensitivity of the latter assay was found to be size dependent. After ultracentrifugation of serum samples from patients with IgA nephropathy, IgA of large and intermediate macromolecular size was detected. It is concluded that the a-IgA-InhBA is useful for the detection of circulating IgA containing immune complexes in IgA nephropathy. PMID- 2212679 TI - Production of murine interleukin-4 and interleukin-5 by recombinant baculovirus. AB - The cDNAs coding for murine interleukin-4 and -5 have been expressed using the baculovirus AcNPV as a vector in insect cells. Interleukins are secreted into the culture medium of virus-infected insect cells at high levels. Recombinant baculoviruses were isolated using a simple and fast selection scheme based on assays for interleukin activity. The cloning strategy described should be generally applicable to the production of any interleukin or other proteins with biological activity in the baculovirus system. PMID- 2212680 TI - Statistical design of ELISA protocols. AB - This paper shows how to obtain accuracy and efficiency in an ELISA analysis by allocating the wells on a 96-well microplate between calibration and determination of unknowns, and by choosing the known concentrations for calibration. The method also can determine how much is lost in precision by using a convenient but non-optimal protocol. PMID- 2212681 TI - Application of the 'area under the curve' method to measure the tumor necrosis factor activity. PMID- 2212682 TI - A novel covalent enzyme-linked immunoassay (CELIA) for simultaneously measuring free and immune complex bound antibodies of defined specificity. I. Application to naturally occurring antipolyamine antibodies in human sera. AB - A simple covalent enzyme-linked immunoassay procedure (CELIA) is described for the routine determination of free and immune complex-bound antibodies in sera. Assays for the latter could not have been performed by adsorption ELISA due to the high ionic strength of the reassociating buffer. For the measurement in human sera of free naturally occurring IgG and IgM antibody directed against the hapten spermine, polycarboxystyrene microtiter plates with covalently coupled spermine were used. For the determination of immune complex-bound antipolyamine IgG and IgM antibody titers, serum was first dissociated at pH 2.3 in tubes and then reassociated at pH 8.1 in the wells of a microtiter plate containing covalently bound spermine. The reactivity of anti-spermine antibodies was increased from 2- to 13-fold after dissociation and reassociation compared to that of non dissociated area. The apparent reaction constant (Rapp.) of free IgG antibodies to spermine in the sera of 19 bronchopulmonary patients with cancer differed significantly from Rapp. values of IgG antibodies having this specificity in ten other patients with non-malignant disease. PMID- 2212683 TI - Characterization of polyclonal anti-peptide antibodies specific for transforming growth factor beta 2. AB - An antiserum was prepared against a synthetic peptide corresponding to the first 29 N-terminal amino acid residues of transforming growth factor beta type 2 (TGF beta 2) from porcine platelets. The anti-TGF beta 2 peptide antiserum appeared to be completely specific for TGF beta 2 in several immunological assays, including enzyme-linked immunosorbent assays, immunoblotting and immunofluorescence experiments. Furthermore, this antiserum completely neutralized the growth inhibitory effect of TGF beta 2 on mink lung carcinoma (ML-CC164) cells and the transforming capacity of this factor on quiescent monolayers of NRK cells in the presence of epidermal growth factor. These data indicate that the N-terminal region of TGF beta 2 may be involved in the biological activity of this growth factor. TGF beta 1 was not recognized by the anti-TGF beta 2 peptide antiserum. The specificity of the anti-TGF beta 2 peptide antiserum for TGF beta 2 appeared to be useful in identifying TGF beta 2 produced by different cell systems and will be helpful in determining possible functional differences between TGF beta 1 and TGF beta 2. PMID- 2212684 TI - Time resolved fluoroimmunoassay of 7-methyl-2'-deoxyguanosine imidazole (ring open). AB - A solid-phase competitive time-resolved fluoroimmunoassay for 7-methyl-2' deoxyguanosine imidazole (ring open) is described, based on highly specific hemocyanin carrier rabbit antibodies, modified with europium chelates. Eu3+ photoluminescence was detected in a novel micellar solution. The assay was validated both by comparing it with an ELISA and by analysing DNA samples, alkylated either 'in vitro' or 'in vivo' by dimethyl sulfate. The proposed assay proved to be sensitive, simple and reliable. It should be of value, together with other immunoassays for methylated DNA bases, in assessing human environmental exposure to alkylating agents such as nitrosamines, thereby providing a powerful tool in epidemiological investigations. PMID- 2212686 TI - Dissociation rate constant of the biotin-streptavidin complex. AB - We measured the dissociation rate constants of the biotin/streptavidin and biotin/egg avidin complexes by following the release of radiolabeled biotin from the preformed complexes in the presence of excess unlabeled biotin. For separation of bound and free labeled biotin we employed ultrafiltration with disposable microconcentrators. The dissociation rate constant for underivatized streptavidin was 2.4 x 10(-6) s-1, or approximately 30-fold higher than that observed for egg avidin 7.5 x 10(-8) s-1). The value for streptavidin was further increased after derivatization with an acridinium ester label. Both biotin binding proteins exhibited a faster initial phase, suggesting binding site heterogeneity due to partial subunit dissociation or denaturation. The convenience of the method and the relatively fast dissociation of biotin from streptavidin render the dissociation rate constant a practical experimental criterion for monitoring the integrity of the binding site during purification and derivatization procedures. PMID- 2212685 TI - Bioassay of interleukin-1 in serum and plasma following removal of inhibitory activity with polyethylene glycol. AB - Serum and plasma normally inhibit the responsiveness of the indicator cells used in bioassays for interleukin-1 (IL-1). A precipitation step with 12% polyethylene glycol (PEG) was found to remove material responsible for such inhibition. The IL 1 bioassay could be performed in the presence of a 3% concentration of PEG and recovery of added natural IL-1 from plasma or serum was essentially complete. PMID- 2212687 TI - Non-specific reactivity of monoclonal antibodies in ELISA due to the presence of an antigen-like structure on the alkaline phosphatase molecule. PMID- 2212688 TI - A turbidimetric assay in an ELISA reader for the determination of mononuclear phagocyte procoagulant activity. AB - A method is described for the simultaneous determination of plasma recalcification time in 60-96 replicates. It is based on turbidimetry in a thermostatic (37 degrees C) ELISA reader photometer. Dose-response curves with thromboplastin showed a double-logarithmic correlation between recalcification time and thromboplastin concentration. Various ways of determining the coagulation time by turbidimetry were compared. Samples of mononuclear cells or monocyte-derived macrophages showed that procoagulant activity (PCA), expressed in thromboplastin units, was directly proportional to the cell number. The method may be of value for the determination of mononuclear phagocyte PCA and for the other applications of plasma recalcification time. PMID- 2212689 TI - Isolation of rat peritoneal mononuclear and polymorphonuclear leucocytes on discontinuous gradients of Nycodenz. AB - Centrifugation of rat leucocytes from thioglycollate-induced inflammatory peritoneal exudate on a discontinuous gradient of Nycodenz with a density of 1106 g/l and an osmolarity of 400 mosmol/l separated the polymorphonuclear from the mononuclear leucocytes. The cells on the interphase between the buffer and the gradient medium contained 96% mononuclear leucocytes with a recovery of greater than 60%, and the bottom fraction consisted of 98% polymorphonuclear leucocytes with a yield of 91%, when an exudate isolated 20 h after the injection of thioglycollate was fractionated. Leucocytes isolated from non-inflamed rat peritoneum could be enriched in the fraction of nonspecific esterase-positive cells from 86% to 96% with a recovery of 82% on a gradient with a density of 1091 g/l and an osmolarity of 325 mosmol/l. The viability of the isolated cells was greater than 95% (trypan blue exclusion test), and there was no measurable reduction in the fraction of phagocytosing cells (latex and opsonized zymosan) after exposure to the hypertonic gradient material. PMID- 2212690 TI - Fluorescein-specific hybridomas derived from primary mice exhibit more stringent growth requirements than do hybrids from pre-immune animals. AB - Although the generation of antigen-specific hybridoma cell lines from animals which have been multiply immunized is now a routine procedure, the derivation of hybridomas following a single in vivo antigen injection has proven to be much more difficult to accomplish. We show that the addition of an interleukin containing supernatant derived from rat spleen cells which have been stimulated with concanavalin A (ConA SN) to hybrids after the initial cloning step results in the consistently successful isolation of IgM anti-fluorescein specific hybridomas. However, addition of the same supernatant to fused cultures simultaneously with the addition of the HAT selection medium results in the loss growing cells. In contrast to the situation with primary hybridomas, the growth of secondary hybridomas is inhibited by the addition of ConA SN at the cloning step. Following successful cloning, there is a time-dependent variation in the sensitivity of all cell lines to ConA SN. PMID- 2212691 TI - A new method for measuring eosinophil activating factors, based on the increased expression of CR3 alpha chain (CD11b) on the surface of activated eosinophils. AB - The observation that activation of eosinophils in vitro with PAF increases the surface expression of the alpha chain of the complement receptor CR3 (CD11b) has been extended to other eosinophil activating factors. CD11b may be detected on activated eosinophils by reaction with mouse monoclonal anti-human CD11b IgG, following the addition of urease-conjugated sheep anti-mouse IgG. CD11b levels were increased on eosinophils after incubation with (a) recombinant colony stimulating factors, IL-3, GM-CSF and IL-5, at concentrations of 100 U/ml, or (b) with eosinophil activating factors, recombinant TNF alpha (1000 U/ml), EAF purified from mononuclear cell supernatants and PAF (10(-6) M). CD11b levels were not affected by IL-1 alpha, IL-2 or IFN-gamma. Unstimulated neutrophils had higher levels of CD11b than unstimulated eosinophils, but neutrophil CD11b was unaffected by IL-3, GM-CSF and IL-5 and was only slightly affected by TNF, EAF and PAF. Polyclonal rabbit antibodies to IL-3 and TNF neutralised their CD11b enhancing activities. The PAF antagonists WEB 2086 and WEB 2170 neutralised the CD11b enhancing activity of PAF. We conclude that measurement of CD11b expression on eosinophils is a convenient method for the assay of eosinophil activating activity. PMID- 2212692 TI - Immobilization of C3b with retention of functional activity. AB - We compared eight commercially available, pre-activated affinity chromatography supports for ability to immobilize C3b that would retain functional activity. Pre activated supports that we studied were: cyanogen bromide activated agarose, N hydroxysuccinimide activated agarose, Reacti-Gel HW-65, Actigel A aldehyde activated agarose, thiopropyl activated agarose, 1,4-bis(2,3-epoxypropoxy) butane activated agarose, Reacti-Gel GF-2000 and tresyl activated agarose. The amount of C3b immobilized by each support varied from 81% for Actigel A aldehyde activated agarose to only 19% for Reacti-Gel GF-2000. We examined the functional capacity of the C3b immobilized on these various supports to participate in the alternative pathway. Immobilized C3b was mixed with factors D and B of the alternative pathway and examined over time for ability to consume factor B hemolytic activity. C3b immobilized on thiopropyl activated agarose consumed factor B at a rate comparable to unbound fluid phase C3b. C3b immobilized on other supports was less active in participating in factor B consumption. Thus, we have demonstrated the ability to immobilize C3b onto a solid matrix with the immobilized C3b retaining the ability to participate in the alternative pathway. This immobilized C3b can be used to fractionate substances with high C3b binding affinity. PMID- 2212693 TI - Induction of anti-idiotypic antibodies to a myeloma protein linked covalently to muramyl dipeptide. AB - BALB/c mice immunized with the MOPC-315 myeloma protein linked covalently to the adjuvant muramyl dipeptide developed antibodies against the MOPC protein. The anti-idiotypic nature of the antibodies was demonstrated by the ability of N epsilon-2,4-dinitrophenyl-l-lysine, a known MOPC-315 ligand, to block antibody binding. Immunized mice developed protection against in vivo challenge with MOPC 315 tumor cells. No anti-tumor cell-mediated cytotoxicity could be demonstrated in immunized and challenged mice. PMID- 2212694 TI - New fluorescent dyes for lymphocyte migration studies. Analysis by flow cytometry and fluorescence microscopy. AB - 16 fluorochromes were examined for their ability to label viable lymphocytes in vitro and yield fluorescence detectable by fluorescence microscopy and flow cytometry. Of these fluorochromes, four intracellular dyes were found to be suitable for in vivo migration studies. They were H33342, the well known DNA binding dye which excites and emits in the UV range, and three fluorescein based cytoplasmic dyes, namely BCECF-AM, Calcein-AM and CFSE which excite and emit in the visible range. Lymphocytes labelled with H33342, BCECF-AM and Calcein-AM were suitable for short term in vivo migration experiments with detection by flow cytometry 2-3 days post injection. In contrast lymphocytes labelled with CFSE, a fluorochrome which can covalently couple with intracellular macromolecules, were detected by flow cytometry up to 8 weeks post injection and thus this fluorochrome is ideal for long term migration experiments. Due to marked differences in fluorescence profiles, BCECF-AM and Calcein-AM could be used for short term double labelling experiments using the flow cytometer in which entry of injected lymphocytes into lymphoid organs was quantified. Similarly, in vivo localization of lymphocyte subpopulations could be examined by fluorescence microscopy utilizing differences in fluorescence excitation and emission spectra of lymphocytes labelled with H33342 and one of the fluorescein based dyes. PMID- 2212695 TI - Fetal bovine serum contains an inhibitor of interleukin-1. AB - The keratinocyte cell line COLO-16 constitutively produces factors with interleukin-1 (IL-1) activity including IL-1 alpha and IL-1 beta. IL-1 activity assayed by thymocyte proliferation from cell supernatants was 20-50% less if cells were maintained in media containing 10% fetal bovine serum (FBS) compared to media without serum 24 h prior to harvest. The increased IL-1 activity in supernatants from cells in serum free media was not due to increased cellular levels of IL-1 alpha or IL-1 beta mRNA. Similarly, IL-1 activity recovered from conditioned supernatants of COS cells transfected with expression vectors containing IL-1 beta cDNA was approximately 22-45% less in cells grown in 20% FBS medium compared to similar cultures grown for 3 days post transfection in 1% FBS. When serial dilutions of recombinant IL-1 were made in buffer containing 10% FBS and assayed by a thymocyte proliferation method, a 30-50% decrease in activity was observed. IL-1 activity was also measured by its ability to induce prostaglandin E2 synthesis by fibroblasts. When COS conditioned supernatants were applied to fibroblast cultures there was 30% less prostaglandin E2 activity from fibroblasts treated with COS supernatants containing 20% FBS, compared to supernatants containing 1% FBS. The inhibitor molecule was partially purified by gel filtration and found to have a molecular weight of approximately 85,000. The presence of FBS in cell-conditioned media significantly reduces the sensitivity of IL-1 detection by bioassay techniques. PMID- 2212696 TI - Linkage of neutrophil response to a mutagen gene (Nrm-1) to the agouti locus in the rat. AB - The ACI or BDIV rats responded with decreased or increased neutrophil levels in blood after the N-methyl-N-nitrosourea (MNU) administration. The F1 hybrids had decreased neutrophil counts, and the BDIV x (BDIV x ACI)F1 backcross offspring showed two phenotypes. The sex of the rats and the neutrophil response to MNU assorted independently. The results indicated that the neutrophil response to MNU was regulated by autosomal gene Nrm-1 with two alleles. The Nrm-1d regulates the decrease and the Nrm-1i regulates the increase of neutrophils in blood after the MNU administration. The results were confirmed by the SKUMIX computer program. We found that the Nrm-1 gene was linked to the agouti locus (chi-square = 10.3, P less than 0.001). The map distance between two genes was 33 +/- 5 cM. The Nrm-1 gene thus resides on the linkage group IV of the rat. PMID- 2212697 TI - HLA-B8,DR3 phenotype and lymphocyte responses to phytohaemagglutinin. AB - Several reports have shown that HLA-B8,DR3 positive subjects may display some changes in immune parameters when compared with HLA-B8,DR3 negative ones and are prone to develop several immunological diseases. In the present study we have analysed the proliferative response to phytohaemagglutin (PHA) in HLA-typed healthy subjects. A twin method was also employed to assess the role of genetic and environmental factors in the regulation of the response to the mitogen. It was not possible to demonstrate any difference in proliferative response to optimal doses of PHA between groups of subjects carrying or not carrying the HLA B8,DR3 phenotype. When suboptimal responses were studied, however, the results showed that lymphocyte responses were significantly decreased in HLA-B8,DR3 positive subjects compared with the negative ones. Moreover, the experiments performed with twins demonstrated that environmental factors were more important than genetic factors in the proliferative response to mitogen. The fact that the HLA-B8,DR3 phenotype affects the suboptimal response to PHA although environmental factors are more important than genetic factors in the response to the mitogen seems of some interest. However, these results could be consistent with the high incidence of autoimmune disorders among HLA-B8,DR3 positive individuals. PMID- 2212698 TI - Biochemical analysis of the rat MHC class I antigens RT1.Aa, RT1.Fa and Pa. AB - In DA strain rats, there are two other MHC class I loci (Pa and RT1.Fa) in the vicinity of the classical class I locus RT1.Aa. The Pa antigen is the pregnancy associated antigen, and it was detected by antibodies elicited in WF females pregnant by DA males without any other immunization. The Fa antigen was detected by a monoclonal antibody raised by alloimmunization. In the present work, the Aa, Fa and the Pa antigens have been compared by HPLC peptide mapping and by isoelectric focusing after their isolation by appropriate monoclonal antibodies. All the three antigens are identical in primary structure with respect to lysine, methionine, asparagine and the aromatic amino acid residues, but they differ from one another with respect to glutamic acid and/or aspartic acid residues. The pI values of the antigens differ slightly. All three antigens have two identical N linked glycans, but the Fa antigen has an additional N-linked glycan. Based on the available amino acid sequence of the Pa antigen, it can be concluded that both Aa and Pa antigens are devoid of glycosylation in the second domain. This lack of glycosylation of the classical antigen Aa is unique for the rat, since classical class I antigens of the mouse show glycosylation in the first and second, and sometimes in the third domain, and those in the human, in the first domain only. The high degree of similarity among the Aa, Fa, and Pa molecules that this study indicates is also unique for the rat, since antigens encoded by different class I genes of the same haplotype are quite disparate in the mouse and human. PMID- 2212699 TI - Inactivation of the H-2Klk gene could involve the substitutions of methylated CpGs. AB - By the isolation of overlapping cosmid clones and 'chromosome walking' studies from the H-2Kk gene, we have obtained cosmid clones encoding the H-2Klk gene from two separate cosmid libraries. The nucleotide sequence of one of the clones was determined. The cloned H-2Klk gene could be transcribed in vitro to give a normal H-2 class I mRNA of 1.7 kb. However, the deletion of four nucleotides in exon 3 of the H-2Klk gene results in a translation termination codon at the beginning of exon 4. In agreement with this, when expressed in human cells, the H-2Klk gene gave a truncated, cytoplasmic polypeptide of Mr 36,000. Therefore, although the H 2Klk gene is homologous to other class I MHC genes in its molecular organization and nucleotide sequence, it is a pseudogene. When compared to the nucleotide sequence of the H-2Kk gene, the H-2Klk gene has undergone many substitutions of methylated CpG residues (meCpG). This represents further evidence to suggest that this gene is inactive. PMID- 2212700 TI - Post-translational polymorphism of human IgA identified by immunoisoelectrofocusing. AB - Immunoisoelectrofocusing (IIEF) reveals a microheterogeneity of human serum IgA controlled by an autosomal polymorphic gene, termed S. The microheterogeneity disappears when sialic acid is removed from serum glycoproteins by neuraminidase treatment. It can be postulated, therefore, that S encodes a sialyltransferase which attaches sialic acid at the outer prosthetic chains of IgA. PMID- 2212701 TI - Identification of a recombinational signal sequence-specific DNA-binding protein(s) of Mr 115,000 in the nuclear extracts from immature lymphoid cell lines. AB - Rearrangements of immunoglobulin genes are mediated by highly conserved heptamer and nonamer recombinational signal sequence. Using a protein-blotting procedure, a heptamer and nonamer recombinational signal sequence-specific DNA-binding protein(s) was examined in the nuclear extracts from lymphoid and nonlymphoid cell lines. Nuclear extracts were subjected to SDS-polyacrylamide gel electrophoresis, and transferred by electroblotting to nitrocellulose filters. Then the filters were hybridized to 32P-labelled synthetic double-stranded heptamer-23bp-nonamer or nonamer-12bp-heptamer recombinational signal sequence probes. A relatively large amount of a DNA-binding protein(s) of Mr 115,000 for both probes was detected in the nuclear extracts from immature B and immature T cell lines. No DNA-binding proteins were detected in a myeloma cell line. Interestingly, this DNA-binding protein(s) might be able to recognize both heptamer and nonamer. Recombinational signal sequence-specific DNA-binding activity of the protein(s) and the presence of the protein(s) in a stage-specific manner strongly suggest that the protein(s) of Mr 115,000 detected here may play an important role in the recombination of Ig and TCR genes. PMID- 2212702 TI - Protection of newborn mice from graft versus host disease by maternal pre immunization. AB - Alloimmunization of BALB/c (H-2d) female mice with allogeneic spleen cells from C57BL/6 (H-2b) or CBA/H (H-2k) mice protects BALB/c offspring from graft-versus host disease (GVH-D) following neonatal intraperitoneal inoculation of high doses of spleen cells respectively of C57BL/6 or CBA/H strains of mice. The mice survived GVH-D over one year after the allogeneic inoculum 24-48 h after birth and they did not show any signs of GVH reaction nor splenomegaly. We show that this phenomenon is antibody mediated and affects the developing immune system of the foetus. Repeated immunization of virgin female BALB/c with anti-H-2b or anti H-2k antisera (Ab1) can equally abrogate GVH-D in their newborn offspring challenged at 24-48 h after birth with allogeneic spleen cells of H-2b or H-2k phenotype. Our results demonstrate that protection from GVH-D is not specific to the immunizing strain and occurs when the neonatal mice are challenged with C57BL/6 or CBA/H spleen cells. There is thus crossreactivity of tolerance against H-2 specificities. In this study we also report on the in vitro cellular immune responses of the surviving GVH-resistant mice and demonstrate that these responses against both the challenge and third party lymphocytes are impaired. PMID- 2212703 TI - Genetic analysis of Leishmania mexicana infection in mice: single gene (Scl-2) controlled predisposition to cutaneous lesion development. AB - Subcutaneous inoculation of Leishmania mexicana amastigotes into the shaven rumps of DBA/2 mice results in a unique 'no lesion growth' phenotype not observed in other mouse strains. Statistical analysis (Kolmogorov-Smirnov and log likelihood tests) of lesion diameters in F1, F2 and backcross progeny from (C57BL/6 x DBA/2) matings indicate that segregation between lesion growth and no lesion growth phenotypes comes under single gene control. The gene has been designated Scl-2 for susceptibility to cutaneous leishmaniasis locus 2. Preliminary mapping studies using 12 of the 26 BXD recombinant inbred mouse strains suggest a location for Scl-2 near Xmmv-8 on a region of mouse chromosome 4 showing homology with human 9p. The identification and mapping of this murine resistance gene could provide an important tool for genetic analysis of susceptibility and resistance to cutaneous leishmaniasis in man. PMID- 2212704 TI - [Length of the kidney and length of the foot. Correlative study during the fetal period]. AB - The renal length growth was studied in 240 specimens taken from 120 staged human fetuses (74 males and 46 females). The gestational age of the fetuses ranged between 10 and 36 weeks postconception. The kidneys were measured for greatest length and the data correlated to fetal foot length by using the allometric method (Y = bXk). Equations and growth curves for males, females and whole sample are presented. The renal length grows with greater velocity in early gestation. These was no growth difference between left and right kidneys. During the third trimester, males fetuses presented renal length significantly greater than females. This study has practical utility in the quantitative determination of renal anomalies. PMID- 2212705 TI - [Endoscopic treatment of ureterocele. The value of antireflux injection of teflon paste]. AB - On the basis of 5 cases, the author show the possibilities of treating certain ureteroceles via an endoscopic approach only with incision of the ureterocele and elimination of the reflux thus created by an injection of teflon paste under the gaping ureterocele. The best indication for this method is an orthotopic ureterocele affecting a non-double ureter, i.e. the ureterocele usually seen in the adult. Orthotopic ureterocele in the presence of double ureter/kidney also seems suitable for treatment in this way. In contrast, ectopic ureteroceles are probably the least suitable indication. PMID- 2212706 TI - [Rigid ureteroscopy and the pulsed laser. Apropos of 325 treated calculi]. AB - A pulsed dye laser (Candela) was used in our lithiasis treatment center during the period 02/88-09/89 to remove 325 calculi in 278 patients, requiring 285 endoscopic instrumentations. The pulsed laser allowed to obtain fragmentation of 318 calculi, 238 of which were reduced to thin sand and 80 to coarser fragments. The latter were either cleared using a Dormia probe or further disintegrated by electrohydrolytic shock wave treatment or extracorporeal shock wave lithotripsy (ESWL). No complication imputable to laser stone fragmentation was noted. Failure of stone clearance was chiefly due to the nature and shape of the stone (black, smooth monohydrated calcium oxalate calculi). The thinness of the laser fiber has made it possible to use small caliber ureteroscopes, thereby increasing the reliability of ureteroscopy. Coupled with ESWL (EDAP LT01), this technique has caused the rate of open surgical removal of ureter confined calculi to fall from 11% to 1%. PMID- 2212707 TI - [Extracorporeal piezoelectric lithotripsy (EDAP LT 01) in the treatment of ureteral calculi. Apropos of a series of 143 cases]. AB - The results for 143 cases of ureteral stones treated by EDAP LT01 were analyzed concerning stone location, ureteral manipulation and treatment position. The ureter was divided into six segments: ureteropelvic junction (UPJ), proximal ureter (PU1 and PU2), mid-ureter (MU), distal ureter (D1 and D2). The overall fracturization rate (FR) was 72%, as detailed below: UPJ (89%, 26/29), PU1 (86%, 13/15), PU2-MU (62%, 15/24), DU1 (59%, 25/42), DU2 (72%, 24/33). Anesthesia or iv sedation were never used for PEL. 24% of the patients underwent retrograde ureteral manipulation (in situ/push back = 108/35). For PU1, the FR was twice as high after retrograde manipulation (in situ/push back = 5/8). For PU2 and MU, the supine position was most common. For UPJ and PU1, it was often better to have the patient lie on his side. For DU1 and DU2, a prone position was necessary. For all stones in DU1, the bladder must be well filled; the FR was higher in DU2 than in DU1. DU2 stones appeared to adhere to the bladder wall or were intravesical (stone in the meatus). The stone-free rate for successfully manipulated ureteral calculi (3 month's follow-up) was 93% (27/29). The stone-free rate for in situ stones at 3 months was 94% (70/74). Extracorporeal piezoelectric lithotripsy combined with stone manipulation is highly efficient in the management of UPJ, PU1 and DU2 stones. The success rate of in situ PEL improves after the operator becomes skilled with the procedure. The advantages of the EDAP LT01 are the absence of pain, no need for anesthesia, and the mobility of the shock wave unit. PMID- 2212708 TI - ESWL for ureteral calculi. Using the Dornier HM 3, HM 3+ and Wolf Piezolith 2,200. AB - In a one year period from July 1985 to July 1986 226 upper and 62 distal ureteric calculi were treated. In situ ESWL represents the therapy of first choice for upper and distal ureteric calculi with a success rate of 81% and 76% respectively. Retrograde mobilization of the calculus was used only in cases where in situ ESWL was impossible because of localization difficulties (obesity, stone close to the spine, skeleton deformation). Although ESWL after successful mobilization succeeded in 95%, retrograde mobilization was possible only in 80%. Antegrade ureterorenoscopy via percutaneous nephrostomy was performed to avoid open surgery after impossible retrograde mobilization and succeeded in 90%. Two second generation lithotripters suitable for treatments without invasive forms of the anesthesia, the modified Dornier HM 3- and the Wolf Piezolith 2,200 were compared in terms of efficacy for ureteric calculi. In situ ESWL was successful with the Piezolith 2,200. In situ ESWL of middle ureteric calculi was successful 81.8% with modified HM 3+, while in situ treatment of middle ureteric calculi was impossible with the Piezolith 2,200 due to insufficient localization with ultrasound of middle ureteric calculi were treated successfully in 71.4% with the modified Dornier HM 3+ and in 64% with the Piezolith 2,200. First clinical experience of ESWL in prone position for iliac ureteric calculi was reported. 8 of 10 cases were treated successfully in situ. PMID- 2212709 TI - [Useful investigations for the prevention of recurring lithiasis (in the absence of anomalies of the urinary tract)]. AB - The prevalence of renal lithiasis and the rate of recurrences in affected patients raises the problem of the minimum number of investigations really needed to arrive at an accurate diagnosis and establish a potentially effective treatment. Stone recuperation is very important as it allows to carry out an accurate analysis of its constituent(s) (frequently heterogenous). Such analysis already brings forth accurate indications as to the etiology. Other biological investigations should be limited after a first episode of kidney stone disease, but recurring lithiasis will necessitate a much more thorough work-up. Recurrences in certain lithiases, such as those caused by urate calculi, are readily prevented by conventional therapy (uricosuric agents, alkalinization of urine). Withdrawal of certain medicines is paramount in iatrogenic lithiasis. Regarding calcium stones associated with hypercalciuria, results from dynamic tests and their pertinence for differentiating between hypercalciuria due to abnormally high digestive absorption and that due to excessive elimination are currently strongly contested. The role of alimentary factors seems extremely important and prescription of adapted diets appears to be quite effective in view of the present lack of crystal formation inhibitors. PMID- 2212710 TI - [Urethrostenosis from Dupuytren to Guyon: "the tools and the men"]. AB - Great progress has been made in the management of urethral narrowing during the second half of the 20th century owing to the appearance of urology as a specialty, to the spinoff of lithotripsy, to the motivation provided by the Argenteuil award and to the refinement of surgical tools. Progress was made in the exploration (impression dilatators, ball exploration) and treatment: permanent or progressive dilatation, cauterization, internal or external urethrotomy. Biographical notes are then given about the surgeons who made this progress possible: Amussat, Benique, Civiale, Desormeaux, Ducamp, Guillon, Heurteloup, Lallemand, Leroy D'Etioles, Maisonneuve, Reybard and Segalas. PMID- 2212711 TI - [Transplantation and tumors of the kidney]. AB - The authors report the case of a woman who was transplanted with a cadaveric kidney. It was a cyst on the kidney; a biopsy was performed: it was a carcinoma. The transplanted kidney was removed. The second case was a man, transplanted with a cadaveric kidney, with a tumor at the lower pole: a tumorectomy was performed: it was a angiomyolipoma. PMID- 2212712 TI - [Duplication of the urethra in a young girl. Apropos of a case]. AB - Duplication of the female urethra is quite uncommon. A case of complete urethral duplication is reported in a 2.5 year old girl seen for pyuria. Physical examination showed and epispadiac meatus with dribbling urine just above a bifid clitoris associated with an orthotopic meatus. The two urethras were patent and situated on the same sagittal plane as seen on the cystography. The treatment consisted of excising the whole epispadic urethra using a combined perineal and suprapubic approach enlarged by symphyseal section for a better repair of the bladder outlet. Postoperatively, the patient was content and free of symptom. The main features of urethral duplication in girl are reviewed. PMID- 2212713 TI - [Supernumerary testis and homolateral varicocele. Apropos of a case, study of spermatogenesis and review of the literature]. AB - Polyorchidism is a rare abnormality. A case is reported of a small scrotal supernumerary testis associated with a large varicocele. A torsion of this testis probably occurred and the vascular pedicle seemed atrophic. Despite abnormal fertility with oligozoospermy the accessary testis was removed. A review of relevant literature is made giving details of embryology of this anomaly. PMID- 2212714 TI - [Preservation of the penis]. PMID- 2212715 TI - [Treatment of renal cysts by percutaneous drainage and alcoholization. Our experience]. AB - Since many years renal cysts have been treated by percutaneous puncture and successive aspiration. The introduction of various sclerosing substances has been associated with this manoeuvre. In our study we examined 44 patients with renal cysts submitted to percutaneous puncture, aspiration and injection with 95% ethanol. We thought right to leave a small pig tail catheter so that the sclerosing substance could be easily and completely eliminated allowing the adhesion of the cystic walls in the following days, without any accumulation of cystic and/or exudative liquid. The follow up (12-24 months) has shown no relapsing in 40/44 cases. Only in 4 patients a cyst was present, but with dimensions lower than 30% of the original volume. PMID- 2212716 TI - [Indications for subcapsular nephrectomy in children]. AB - Subcapsular nephrectomy has advantages over classical nephrectomy in such cases with the kidney adhered to adjacent structures. Actually, to the usual indications, as chronic renal infection and previous renal surgery, we add up the nephrectomy of transplanted kidney, that forms our main indications. In our review of medical literature we haven't found any references about subcapsular nephrectomy in pediatric age. We report 31 cases of subcapsular nephrectomy from a total number of 121 nephrectomies performed in children during the last 20 years. We analyse the indications, surgical management, postoperative course and latter complications of subcapsular nephrectomy. PMID- 2212717 TI - [Results of detubulate enterocystoplasty. Apropos of 17 cases]. AB - From January 1988 to October 1989, 17 patients underwent radical cystectomy for bladder cancer. They had a bladder replacement by Hautmann pouch. Good results were obtained after a period of observation of 6 to 24 months. Two patients died. Hyperchloremic acidosis was observed in 20% cases. The urinary continence was achieved in 13 patients who were willing to wake up twice every night. One patient preferred the collecting device. Our study showed that the Hautmann pouch is a particular low pressure reservoir with a capacity of 200 ml to 800 ml, and assessed the mechanism of loss of urine at night in one case. The urinary continence was achieved after a good training period and depended on patient's cooperation. This technique permitted to obtain a very satisfactory diurnal and nocturnal continence in our patients, however a longer follow up is mandatory to confirm the efficiency of this method on long term basis. PMID- 2212718 TI - [Cancer of the prostate. Computed tomography and magnetic resonance imaging in the assessment of extracapsular extension]. AB - The stage of the tumor is commonly underestimated prior to radical prostatectomy for carcinoma. Can the growth of clinically localized carcinomas beyond their capsule be predicted with the modern medical imaging techniques (MRI and CT)? On the basis of 30 successive prostatectomies, we conclude that CT is ineffective. On the contrary, MRI seems to be an effective technique for this indication. However, no examination yet is better than clinical assessment. PMID- 2212719 TI - [The value of cytological grading of prostatic adenocarcinoma. Comparison of the clinical state, the Gleason score and grade in 69 cases]. AB - During a two-year period, 69 positive prostatic fine-needle cyto-aspirates were selected for a comparison between the cytological grade and the clinical data, and also with the Gleason score and grade obtained with needle-biopsy. The cytological grade is independent of stage, except for grade III that indicates an advanced tumor (T3-T4). On the other hand, the cytological grade provides valuable indications on the histopathological differenciation according to Gleason, with no grade II inferior to Gleason score 5, and no grade III inferior to Gleason 7. 90% of cytological grades III are Gleason grade 4. According to recent studies, we believe that the cytological grade I is related to invasive or in-situ carcinoma, but also to high-grade intra-ductal dysplasia. Thus, it is not surprising to find no correlation between grade I and the clinical status, nor between grade I and the Gleason score and grade, though grade I (or DIC 3) has a good diagnostic value. PMID- 2212720 TI - [Sclerotherapy of varicocele. Efficacy of radiological, clinical and seminal treatment]. AB - Between december 1983 and april 1989, percutaneous retrograde sclerotherapy of varicocele was successfully performed on 364 patients. A 5% solution of sodium morrhuate and benzylic alcohol (Varicocid) was administered through a coaxial balloon catheter inserted into the spermatic vein. 10 of the patients had relapses after surgery. Long-term follow-up was available for 268 patients (73.6%). Three of them had incomplete relapses after sclerotherapy. In terms of spermatologic improvement, sclerotherapy appeared to be effective in the treatment of varicoceles. In our experience, sclerotherapy is a safe effective procedure to be preferred to surgery in the management of varicocele. PMID- 2212721 TI - [Cockett's syndrome and retro-iliac ureter. A previously unknown and original association apropos of a case and review of the literature]. AB - The authors report a case of Cockett's syndrome discovered by ilio--cava angiography at a patient who was operated on a bilateral retro-iliac ureter which occasioned an important renal insufficiency. After a review of the literature, it appears it is the first case published with such a pathologic association mentioned. PMID- 2212722 TI - [Oncocytoma and calcification. A rare association]. AB - The oncocytoma constitutes 3-6% of the kidney neoplasiae. The authors report one case of calcified kidney tumor, Its presentation as a calcified kidney mass is exceptional and is not present in the largest series of calcified kidney tumors. The calcification prognosis is much debated, even more in the case of oncocytoma due to the very limited series available. For calcified kidney tumor, the oncocytoma should be included as one of the differential diagnosis, even if it is not very frequent. PMID- 2212723 TI - [Urological problems in separating conjoined twins. Ischiopagus tripus type]. PMID- 2212725 TI - Examination of stratum corneum barrier function in vivo by infrared spectroscopy. AB - It is generally accepted that the stratum corneum (SC) is the least permeable layer of the epidermis. Histologically, though, the SC is a non-uniform, inhomogeneous membrane, and the question "Is barrier function distributed uniformly across the SC thickness?" has been posed. To address this issue, human ventral forearm SC has been studied in vivo by attenuated-total-reflectance Fourier-transform infrared spectroscopy during the course of sequential tape stripping. Because the intercellular lipids of the SC and the degree of hydration of the membrane have been shown to be crucial determinants of barrier function, attention has been focused on the spectral features, which report specifically on these parameters. The degree of disorder of the SC intercellular lipids has been found to decrease over the outer cell layers (up to three tape-strips) and then to remain essentially constant. The amount of lipids decreases similarly such that a 60% reduction (relative to the "no-strip" baseline) is observed after about four tape-strips. A plausible explanation for these measurements is that the lipids near the surface are a mixture of (a) "true" intercellular lipid (which is expected to be highly ordered), and (b) sebaceous lipid (which contains much greater amounts of low-melting components, such as fatty acids). The sequential infrared (IR) spectra provide at least circumstantial evidence to support this hypothesis. As expected, the IR spectra show that SC hydration increases from the surface towards the SC-stratum granulosum interface. Taken together, the results imply that the SC is indeed non-uniform. The properties of the outer layers (those removed by the first 3-4 tape-strips) change significantly with increasing depth.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212724 TI - The innermost cell layer of the outer root sheath is positive with Ki-67. AB - The expression of a cell proliferation-associated human nuclear antigen was immunohistochemically studied in human anagen hair and hair follicles using the monoclonal antibody Ki-67. The reaction of Ki-67 in mature anagen hair follicles was observed in the hair matrix cells and outer root sheath (ORS) cells. Nuclear staining was seen in a small number of matrix cells and in some ORS cells; this finding corresponded to the thymidine or bromodeoxyuridine labeling studies previously reported. In addition, there were two different patterns of cytoplasmic staining in the ORS: strong staining of the innermost cells (IMC) and weaker staining of the other ORS cells in the isthmus. Ki-67 reactivity of the IMC layer was observed at each stage of anagen and was regularly seen from the upper bulb to the isthmus. Ki-67 is a commercially available antibody that detects cycling cells. However, the IMCs in anagen hair follicles showed cytoplasmic labeling by Ki-67 from the matrix cells in the upper bulb to the distal portion of the isthmus. PMID- 2212726 TI - Recruitment of mononuclear cells by endothelial cell binding into wounded skin is a selective, time-dependent process with defined molecular interactions. AB - Wound healing involves a complex series of interactions between cells in the dermis and epidermis, and important relationships exist between keratinocytes and resident dermal cells. Monocytes and lymphocytes secrete cytokines that are capable of stimulating dermal repair and influencing keratinocyte and fibroblast migration and proliferation, although the mechanism by which mononuclear cells are recruited into the wound is unknown. We have tested the hypothesis that in wounded skin specialized endothelial cells are induced to mediate peripheral blood mononuclear cell (PBMC) emigration from the vasculature into the dermis. For this purpose, partial-thickness wounds made with a keratome on the backs of domestic pigs were excised 0 to 9, 12, 15, and 21 d after wounding. The biopsies were then tested for the capacity to adhere selectively to PBMC. The results indicated that PBMC overlaid onto sections of wounds from day 4 to 15 adhered selectively to dermal endothelium, with two distinct peaks of adherence observed on day 7 and day 12. In contrast, PBMC did not adhere to the tissue sections when overlaid onto frozen sections of normal skin or 0-, 1-, 2-, 3-, and 21-d-old wounded skin. Additional studies on the binding properties of PBMC subsets revealed that monocytes adhered maximally at day 7, whereas T cells adhered optimally at day 12 post-wounding. Furthermore, the adhesion process was energy and magnesium dependent but not calcium dependent and involved surface protein and carbohydrate moieties on PBMC surface. Pre-treatment of PBMC with monoclonal antibodies against the LFA-1 adhesive receptors inhibited the binding by greater than 80%, suggesting that LFA-1 adhesive receptors play an important role in the binding process. These studies provide evidence that the recruitment of monocytes and lymphocytes into wounds is an active, dynamic, and regulated process mediated at least in part by specific adhesive interactions between mononuclear leukocytes and dermal endothelial cells. PMID- 2212727 TI - Ultrastructure and three-dimensional organization of the telangiectases of hereditary hemorrhagic telangiectasia. AB - We studied 10 cutaneous telangiectatic lesions of hereditary hemorrhagic telangiectasia (HHT), ranging in size from pinpoint to 2 mm, by light and electron microscopy. Four representative lesions were reconstructed by computer from serial 1- or 2-mm plastic embedded sections. The earliest clinically detectable lesion of HHT is a focal dilatation of postcapillary venules, which continue to enlarge and eventually connect with dilated arterioles through capillaries. As the vascular lesion increases in size, the capillary segments disappear and a direct arterio-venous communication is formed. This entire sequence of morphologic events is associated with a perivascular mononuclear cell infiltrate in which the majority of cells are lymphocytes and the minority are monocytes/macrophages by ultrastructure. Comparison of these findings with the telangiectatic mats of scleroderma and cherry angiomas revealed that the former, previously shown to be composed of dilated postcapillary venules, are also associated with perivascular infiltrates, but the latter, which are produced by capillary loop aneurysms, are not. PMID- 2212729 TI - Abstracts for the 20th annual meeting of the European Society for Dermatological Research. Turin, Italy, June 9-12, 1990. PMID- 2212728 TI - Delayed antigen presentation by epidermal Langerhans cells to cloned T h1 and T h2 cells. AB - Langerhans (LC) cells require incubation with protein antigen for several days before the cells effectively stimulate proliferation of cloned, H-2 restricted, antigen-specific T h cells. In contrast, splenic antigen-presenting cells are immediately effective. LC are immediately competent, however, if an immunogenic peptide rather than the intact protein is the immunogen, indicating that resident or unchallenged LC have the required class II MHC and can provide the signals necessary for T-cell proliferation but may lack the capacity to internalize or cleave protein antigens. We propose that delayed antigen presentation by LC may be intrinsic and advantageous for promoting early systemic immunity. LC stimulate cloned T h1 and T h2 cells equally well, suggesting that LC may not limit or bias the type of immunity that occurs with cutaneous antigenic challenge. PMID- 2212730 TI - Leprosy control within urban primary health care. PMID- 2212732 TI - Screening of registered leprosy cases and its effects on prevalence rate. AB - Prevalence rates of leprosy in 6 endemic districts in Andhra Pradesh, India with a population of 168.71 lakhs (1981 census) were studied before and after screening of registered cases. The screening was carried out as part of multidrug treatment project implementation. After such screening a sharp fall in the registered prevalence rate, by 26.2% on the average, was observed in all the districts. About 34.8% of the total cases were declared as Released from control. The implication of these findings regarding registered cases fit for such release and the overall registered prevalence rates in the country must be kept in mind. PMID- 2212731 TI - Cultivation in vitro of acid-fast nocardioform chemoautotrophic bacteria from mouse foot-pads infected with human strains of leprosy bacillus. AB - Four acid-fast nocardioform bacteria could be isolated and cultivated as pure cultures in vitro from mouse foot-pads (MFP), which were infected with serially passaged strains of human leprosy bacillus; the liquid mineral medium, such as paraffin urea minimal (PUM), paraffin gelatin minimal (PGM), gelatin minimal (GM), and GM agar (GMA) slants containing only simple sources of C and N were used, just like the human and the armadillo isolates of these organisms reported earlier. Morphologically, metabolically and enzymologically, these were closely related to the previous ones and were also chemoautotrophic in nature. Serologically there appears to be a heterogenicity in these isolates, i.e., some of them showing higher affinity to nocardioforms while others showing significant binding to several mycobacteria. Normal (uninfected) mouse foot-pad harvests were not found to harbour such organisms. PMID- 2212733 TI - Leprotic keratopathy in India. AB - Corneal affections cause severe ocular morbidity in leprosy. Poor nutrition and low socio-economic status make the eyes prone to repeated secondary infections which makes the pattern of corneal disease in this country different from that reported in western literature. A study of 250 patients shows that leprotic keratopathy has 4 different patterns. Primary leprous keratitis was seen in 56.5% of cases, while secondary leprous keratitis (groups B, C & D) constituted 57.7%. In the latter group the ocular morbidity could be prevented by controlling infection and prevention of concomitant diseases. Cases of lepromatous leprosy showed a consistently higher incidence of different types of corneal involvement than tuberculoid cases. PMID- 2212734 TI - Early infection with M. leprae and antibodies to phenolic glycolipid-I in the nine-banded armadillo. AB - Nine-banded armadillos were intravenously infected with 10(9) M. leprae. IgM antibodies to PGL-I were evaluated three times during the six months before and every two months after the infection. A thorough autopsy examination was done on animals that died or were sacrificed at intervals of 3, 4, 6, 12, 15 and 18 months after the infection. Three animals which had acquired the infection in the wild and one experimentally infected animal showed significant increases in antibody levels corresponding to their high bacterial load. In the other five experimentally infected animals, M. leprae infection was established in the cells of the reticulo endothelial system (RES) long before the IgM antibody levels to PGL-I became positive. It is possible that in human leprosy also M. leprae may enter and multiply in the RES initiating antibody production during the incubation period before clinical disease with neuritis becomes manifest. PMID- 2212736 TI - Fibrinolytic phenomenon in leprosy. AB - Fibrinolytic activity in eighty-one patients with different types of leprosy and thirty-two normal healthy controls was studied by Euglobulin Lysis Time Method, Fibrinolytic activity was markedly decreased in patients with lepromatous leprosy and those with ENL reaction. Decline in fibrinolytic activity during ENL was independent of frequency of attacks. Fibrinolytic activity was partly restored after subsidence of ENL reaction, though it failed to attain normal levels. Cutaneous vasculitis seems to be most probable cause of fall in fibrinolytic activity in lepromatous leprosy and ENL reaction. PMID- 2212735 TI - Non-pruritic eczemas as presenting manifestation of leprosy. AB - Three patients who presented with eczemas as manifestation of leprosy are described. One of them having lepromatous leprosy had extensive areas of acquired ichthyosis. He developed asteatotic eczema on the legs. The pathophysiologic mechanisms for the development of ichthyosis and asteatotic eczema in this patient are briefly discussed. The second patient, with tuberculoid leprosy, presented with allergic contact eczema due to neomycin which he had applied over the plaque for scaling and crusting. The third patient, also with tuberculoid leprosy, presented with features of nummular eczema. Dryness of the skin that resulted from leprosy had led to the development of nummular eczema in this case. One peculiarity noted in all these eczemas was that they were non-pruritic. PMID- 2212737 TI - Thyroid function in leprosy. AB - Thyroid function tests were carried out in 43 cases of leprosy. The study subjects included cases of tuberculoid, borderline and lepromatous leprosy and those with lepra reaction. The parameters studied included serum cholesterol, protein bound Iodine, serum T3 level and serum T4 levels. The levels of serum cholesterol and protein bound Iodine were normal in all the four groups of leprosy patients. However, the mean serum T3 and T4 were low in all the four groups. The difference in the levels of serum T3 was statistically significant only in the lepra reaction group. The levels of T4 were statistically significantly decreased in borderline leprosy, lepromatous leprosy and in lepra reaction. PMID- 2212739 TI - Reported in vivo structures found in LL cases correlate with the morphological entities of in vitro cultures. PMID- 2212738 TI - Serum iron and total iron binding capacity in leprosy patients. AB - Serum Iron and total Iron binding capacity was estimated by Ramsay's Method in 40 leprosy patients having different types of leprosy and 20 normal subjects serving as controls. Significantly low serum Iron and total Iron binding capacity were observed in lepromatous leprosy patients. PMID- 2212740 TI - Possible multiplication of M. leprae (?) on skin and nail bed of a laboratory worker. PMID- 2212741 TI - Rifampicin induced shock--a case report. PMID- 2212742 TI - Dapsone syndrome with polyarthritis: a case report. PMID- 2212743 TI - Leprosy in a patient with chronic lymphatic leukaemia. PMID- 2212744 TI - A Rosetta Stone for chronic pancreatitis? PMID- 2212745 TI - Pancreatic insufficiency. Duodenal and jejunal pH, bile acid activity, and micellar lipid solubilization. AB - To investigate the course of postprandial lipid solubilization in nine patients with chronic, alcoholic pancreatitis, luminal contents were aspirated from the proximal part of the jejunum for 180 min after a meal containing 1.5% fat. Six of the patients had pancreatic insufficiency, whereas three patients were without insufficiency. pH was measured continuously at two sites: at the level of the papilla of Vater and the aspiration site. The fraction of bile acids in the micellar phase of the jejunal aspirates correlated positively to both pH in the aspirates (p less than 0.05) and the fraction of fat solubilized (p less than 0.02). pH was below 4.0 for a longer period of time in the patients with insufficiency, compared to the patients without. However, pH fluctuated rapidly, and there was no correlation between the continuously measured values at the aspiration site and values in the aspirates. Lipid solubilization was not correlated to the lipase activity in the aspirates. We conclude that acidic bile acid precipitation most likely plays a dominant role in the pathophysiology of pancreatic steatorrhea although the methods available are too crude to disclose the precise course of events. PMID- 2212746 TI - Volume and enzyme kinetics of human pancreatic secretion after endogenous stimulation with the Lundh test meal. AB - The present study was undertaken to investigate the volume and enzyme kinetics of human pancreatic secretion, after endogenous stimulation with a Lundh test meal, and evaluate the most reliable enzyme and collection period. The prestimulatory volume rates did not differentiate normal from pathologic pancreatic function. After ingestion of the test meal, the immediate increase in volume secretion was identical in healthy subjects and patients with pancreatic insufficiency. The latter showed a drastic reduction of prestimulatory and postprandial enzyme secretion. Cimetidine taken orally 12 and 2 h before the test meal study had no effect on volume and enzyme secretion and endogenous CCK release. Especially in severe pancreatic insufficiency, this modification simplified the performance of the Lundh test. The estimation of lipase and trypsin gave a significant correlation between Lundh test and secretin-cerulein test. The endogenous stimulation by Lundh test meal is a reliable test for routine diagnostic and scientific purposes. PMID- 2212747 TI - Operation of choice for resectable carcinoma of the head of the pancreas. AB - What is the best procedure for resectable carcinoma of the head of the pancreas? In order to respond to the question, a retrospective study was performed based on 510 cases with carcinoma of the head of the pancreas that were experienced from 1975 to 1984 at nine major surgical institutions in Japan. Laparotomized cases (504) were divided into four groups according to operative procedures: pancreatoduodenectomy (PD), total pancreatectomy (TP), regional pancreatectomy (RP), and palliative operation (PO). The postoperative cumulative survival rate (PCSR) was calculated on each group. Although the five year survival rate of PO was 0, those of PD, TP, and RP were 11.2, 4.6, and 4.5%, respectively. There was a significant difference between PD and TP (p less than 0.01) according to generalized Wilcoxon's test. TNM stage grouping was applied to 447 cases that had adequate descriptions on T, N, and M categories. PCSR was calculated on PD, TP, and RP at each stage. It was found in Stage III that survival curve of PD was significantly higher than TP (p less than 0.01), according to generalized Wilcoxon's test. It seems that PD is the best procedure, but it should be accompanied by extensive lymph node and retroperitoneal tissue dissection. PMID- 2212748 TI - Development of carcinoma in chronic calcific pancreatitis. AB - Development of carcinomas of the pancreas over an underlying chronic pancreatitis is a rare event. Diminution of pancreatic calcification, following the development of carcinoma, has been previously reported only once. We report another such case. PMID- 2212749 TI - [Significance of nasal carriage of methicillin-resistant Staphylococcus aureus (MRSA) by medical staff in nosocomial infection]. AB - Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important microorganisms in nosocomial infection. Healthy medical staff working in MRSA endemic wards are known to have MRSA in their nasal cavity, swabs, but the significance of their positive nasal swab cultures in infections among the patients has not been confirmed. The purpose of this study was to compare the antibiotic susceptibility and coagulase typing of strains isolated from the infected patients and from nasal swab cultures of medical staff working in ICU. Twenty-six nurses and 20 doctors working in ICU where MRSA was endemic were examined. Six nurses and 10 doctors gave positive nasal swab cultures for S. aureus, and 2 of the nurses' strain and 5 of the doctors' strains were methicillin-resistant. These strains were sensitive to IPM, GM, MINO and OFLX, while the strains clinically isolated from infected patients were resistant to these antibiotics. MRSA isolated from nasal swab cultures from medical staff developed marked resistance to IPM, GM, MINO, and OFLX by incubating with these drugs, whereas they remained sensitive to VCM when they were incubated in VCM containing medium. Methicillin-sensitive S. aureus (MSSA) isolated from nasal swab cultures of medical staff became resistant to DMPPC, CMZ, in addition to IPM, GM, MINO, and OFLX, but these strains did not develop resistance to VCM. Resistance to these drugs developed by incubating with these drugs did not diminish by incubating in drug-free medium for 3 weeks. The patients infected by MRSA had been previously given several kinds of antibiotics, whereas the medical staff had not been exposed to any kind of antibiotics during the same period. (ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212750 TI - [Efficacy of acellular pertussis vaccine]. AB - An outbreak of pertussis occurred in one room of a residential facility where 19 children aged 5 to 36 months were residing. They were prospectively surveyed to estimate the efficacy of acellular pertussis vaccine. Among the 19 residents, 9 were immunized with acellular pertussis vaccine. Among the 19 residents, 9 were immunized with acellular DTP vaccine and 10 were unimmunized. The spread of pertussis was surveyed bacteriologically and serologically for 2 months. Among the 9 immunized, 7 children acquired the laboratory-confirmed pertussis and 1 of the 7 developed the typical symptoms (whooping or paroxysmal coughing attack lasting for 14 days or more). Among the 10 unimmunized, 7 children acquired the laboratory-confirmed pertussis and 6 of the 7 developed the typical symptoms. There was no difference in the rate of secondary infection (7/9:7/10), but there was a significant difference in the rate of development of the typical symptoms (1/7:6/7 p less than 0.05). The point estimate of protective efficacy of the acellular DTP vaccine against typical pertussis was (6/10 - 1/9)/(6/10) x 100 = 81%. It was concluded from these findings that acellular DTP vaccine could not prevent the infection of Bordetella pertussis, but could prevent the development of the typical symptoms. PMID- 2212752 TI - [Cross protection between an encapsulated strain of Staphylococcus hyicus and an encapsulated strain of Staphylococcus epidermidis]. AB - Strain ST67P of Staphylococcus hyicus was capsular type I (++)/II(+) of S. epidermidis as determined by the method of Ichiman. To mice immunized with heat killed vaccine of strain ST67P, homologous strain and strain ATCC 31432 (capsular type I), SE-360 (capsular type II) and SE-10 (capsular type III) of S. epidermidis were injected intraperitoneally into mice, then, the viable cell number of the organisms in the peritoneal cavity were enumerated of 30 minutes and 20 hours after the injection. Results showed that the viable cell number of the homologous strain and strain ATCC 31432 was remarkably decreased at 20 hours after the injection, however, the cells were increased with strain SE-360 and SE 10. Passive protective activity of rabbit anti-ATCC 31432 serum was absorbed either with homologous strain or strain ST67P in the mouse, however, protective activity of anti-SE-360 strain serum and anti-SE-10 strain serum was not absorbed with these organisms although the activity was absorbed with homologous organisms. With an ultrathin section preparation of strain ST67P conjugated with ferritin-labelled rabbit anti-homologous strain serum, numerous ferritin granules surrounding the outermost layer of large capsule were electronmicro-scopically demonstrated. In the same organisms treated with ferritin-labelled anti-ATCC31432 strain serum, the all walls were surrounded by a relatively thinner capsule and a number of ferritin granules were located in the outermost layer of the capsule. However, with the organisms treated with ferritin-labelled anti-SE-360 strain serum only a number of ferritin granules were shown on the surface of the cell walls, and neither capsule nor ferritin granules were exhibited in the organisms treated with ferritin-labelled anti-SE-10 strain serum. PMID- 2212751 TI - [Seroepidemiological analysis of the age specific prevalence of anti HTLV-I in Miyazaki Prefecture]. AB - Antibody for HTLV-I in sera from 11,224 residents in Miyazaki Prefecture, Japan, was determined by indirect immunofluorescent antibody method to compare age- and sex-specific antibody prevalence among three geographically divided areas of the prefecture. There was a significant difference in the positive rate of older age groups among three areas, 9.0% for the northern part, 14.5% for the southern part and 8.4% for Miyazaki City, in spite of little variation in younger age groups. A marked rise of positive rate in the southern part at the age of 40th was observed, which suggests that changes of some conditions for mother-to-child transmission happened in the time of their birth. Six seroconversions were observed by the follow-up study for five years of the 971 residents. They were between 28 and 38 years of age, four men and two women. This may provide another reason for the increase in antibody positive rate by age in the adult. However, it could not be investigated if the seroconversion was caused by a horizontal transmission from their spouse. The possibility of the long latency of the virus in man as in the experimental animal may also have to be considered. PMID- 2212753 TI - [Identification of acinetobacter species isolated from human infections based on a new classification by Bouvet and Grimont]. AB - The genus Acinetobacter was recently re-classified by Bouvet and Grimont who described four new species, A. baumannii, A. haemolyticus, A. johnsonii and A. junii, and five unnamed genospecies, with a re-definition of A. calcoaceticus and A. lwoffii which appeared in the Approved Lists of Bacterial Names, 1980. One hundred and twenty-eight clinical isolates previously identified as Acinetobacter were retrieved from storage and re-characterized by using a system based on the grouping reactions described by Bouvet and Grimont. Of these 86.7%, 2.3%, and 1.6% were identified as A. baumannii, A. junii and Acinetobacter genospecies 11, respectively, and the remaining 9.4% of the cultures were unidentified. None of the cultures identified as A. calcoaceticus and A. lwoffii was included in the 128 cultures. PMID- 2212754 TI - [Comparison of three methods for detecting Campylobacter pylori and measurement of human antibody titers against the whole organisms]. AB - In order to detect Campylobacter pylori in the gastric mucosa, three different methods as 1) culture of the organisms, 2) immunostaining by monoclonal antibody against the cells, and 3) urease test were compared. In the disease group, positive % of each methods was 64, 75 and 74. However, positive % common to the three methods was only 48. The corresponding rate of culture and urease tests, and that of culture and staining methods was 81% and 60%, respectively. Therefore, it was concluded that urease test was a useful method, and that the three methods were necessary to confirm the existence of the organisms in the gastric mucosa. Total positive % of culture and staining methods in disease and control groups was 77 and 31, respectively, indicating that positive % of the disease group was much higher than that of the control group. Anti C. pylori titer was compared between culture-positive and culture-negative patients by ELISA. The titer of the former was significantly higher than that of the latter. PMID- 2212755 TI - [Serovars, drug susceptibility and conjugative R plasmids of Salmonella isolated from patients with sporadic cases of diarrhea in Yamanashi Prefecture (1985 1989)]. AB - A total of 391 strains of salmonella isolated from patients with sporadic cases of diarrhea during the period from April 1985 to June 1989 in Yamanashi Prefecture, were tested for their serovars, drug susceptibility and conjugative transmissible R plasmids. The results can be summarized as follows: 1) The isolates were serologically classified into 35 different serovars. The predominant serovars were S. Typhimurium (24.8%), S. Litchfield (9.2%), S. Oranienburg (9.0%), S. Enteritidis (7.9%) and S. Hadar (6.1%). 2) Serovars of S. Hadar, S. Brandenburg, S. Chester, S. Chailey, S. Oslo and S. Inchpark were isolated from human sources for the first time in Yamanashi Prefecture. 3) Monthly frequency of isolates were August (17.3 strains), September (11.3 strains) and May (10.6 strains). 4) The predominant ages of isolates were 2 years of age (17.1%), 1 years of age (15.1%), 3 years of age (11.2%), under 1 years of age (10.7%) and 4 years of age (9.8%). 5) The rate of isolates from male were higher than female. (Male: 57.5%, Female: 42.5%). 6) The frequency of resistant isolates was 45.8% in the period. The most predominant resistance pattern was SA.SM.TC.CP.KM.ABPC resistance (11.2%). Conjugative transmissible R plasmids appeared in 41.3% of the resistant strains. 7) The number of resistant strains of S. Typhimurium was 57 out of 97 strains (58.8%). PMID- 2212756 TI - [A case of sepsis caused by Edwardsiella tarda complicated panophthalmitis and pyogenic spondylitis]. AB - Edwardsiella tarda (E. tarda) is gram negative enterobacteriaceae which has been found generally in animal hosts and occasionally in human feces. We have reported a case of sepsis caused by E. tarda, complicated panophthalmitis and pyogenic spondylitis. A 39-year old patient suffered from fever, polyarthralgia and lumbago. We performed blood culture, from which E. tarda was isolated. Spinal CT scan showed destruction and osteogenesis of the fourth and fifth lumbar vertebral body and cranial CT scan showed destruction of the right lens. So we diagnosed sepsis with pyogenic spondylitis and panophthalmitis. We suspected that chronic ethanol administration reduced the resistance to infection of E. tarda which caused sepsis. PMID- 2212757 TI - [Liver abscesses successfully treated by intraportal administration of amphotericin B in a case of acute myeloblastic leukemia (M2)]. AB - A 46-year-old male was admitted to our hospital because of relapse of acute myeloblastic leukemia (M2). Remission was successfully reinduced after reinduction chemotherapy consisting of daunorubicin, cytosine arabinoside, etoposide and vincristine, but was complicated by neutropenia. After the therapy, the patient had persistent fever of about 38 degrees C despite broad-spectrum antibiotics therapy and the patient developed pain in the right quadrant of the abdomen. The white blood cell count rose to 23000/mm3. Liver function tests showed abnormal findings mainly consisting of an elevated serum alkaline phosphatase level. Ultrasonography showed multiple hypoechoic lesions in the liver and CT scans also revealed multiple low density areas. Therefore he was suspected of having a complication of liver abscesses. Amphotericin B was administered 75 mg/day intravenously every other day. A percutaneous liver biopsy was performed, but was not diagnostic. Blood cultures were negative for pathogens. Amphotericin B was administered up to a cumulative dosage of 2.3 g, but the patient remained febrile. Then he had an exploratory laparotomy and an open liver biopsy. The liver biopsy samples showed fungal elements proved by PAS staining. A catheter was inserted into the portal vein. Administration of Amphotericin B was started 20 mg daily through the catheter. The temperature fell to normal after institution of this therapy. The abnormal findings in CT scans almost disappeared and the inflammatory findings became negative after he had received intraportal administration of Amphotericin B over three months. Through the analysis of this case study, we confirmed that the intraportal administration of Amphotericin B was effective to the intractable liver abscesses due to fungi. PMID- 2212758 TI - [A case of Pneumocystis carinii pneumonia with hyperinfection of Strongyloides stercoralis complicated with smoldering adult T-cell leukemia]. AB - A 43-year-old woman visited a clinic for an attack of bronchial asthma which she had been suffering since her childhood. She was treated with prednisolone which was used for the first time. Two weeks later, she had a fever and her chest X-ray showed diffuse reticulonodular shadows on both middle to lower lung fields. In spite of the use of antibacterial drugs, her symptoms such as cough, dyspnea, malaise and fever increased. It was revealed that she had Stronglyoides sterocoralis in the stool. She was referred to our department for treatment and further examination. Transbronchial lung biopsy (TBLB) was performed, and cyst of Pneumocystis carinii were histologically detected in the lung specimen. Anti human T-lymphotropic virus type 1 (HTLV-1) antibody in the serum was 1:4,096 less than. Typical adult T-cell leukemia (ATL) cells were also observed in the peripheral blood smear at the rate of 10-15% of leukocytes. The parasite was observed in the sputum too. We diagnosed her as having Pneumocystis carinii pneumonia with hyperinfection of Strongyloides stercoralis complicated with smoldering ATL, and the pneumonia might have been induced by steroid therapy (total doses of 500 mg, for 25 days). After sulfamethoxazole-trimethoprim (ST compound) was used for the Pneumocystis carinii pneumonia, her symptoms markedly subsided, and the chest X-ray findings turned to normal by 45 days after the treatment. Thiabendazole was initially administered for the Strongyloidiasis and the parasite temporarily disappeared from both sputum and stool. Then pyrvinium pamoate and mebendazole were used, but the parasite could not be completely eradicated in the stool. We did not treat the smoldering ATL because there were no symptoms. We have been looking after her as an outpatient now, and she has neither symptoms nor signs. PMID- 2212759 TI - [A successfully treated case of infective endocarditis due to Candida tropicalis]. AB - A 34-year-old man, a heavy drinker, was admitted with a high fever and hematuria two months previously. Surgery was performed for acute sever pancreatitis and postoperatively antibiotics were administered with intravenous hyperalimentation. After discharge he was readmitted and infective endocarditis was strongly suspected because of high fever, hematuria, Osler's nodes, Janeway's lesions, splinter hemorrhages and mitral regurgitation. Penicillin G in combination with Gentamycine therapy was started on the first hospital day. On the second hospital day, blood culture revealed Candida tropicalis so Miconazole therapy was commenced. On the forth hospital day, he underwent surgery for replacement of a mitral prosthesis with a prosthetic valve because he had embolus in the radial artery. Despite intensive antifungal therapy, he showed no improvement in clinical symptoms. Then we changed the antifungal drug from Miconazole to Amphotericin B and 5-fluorocytosine. On the 109th hospital day, his clinical symptoms improved. Antifungal therapy was halted and at present 10 months later, he is healthy. PMID- 2212760 TI - [An in vitro study on the treatment of complicated cystitis using an automatic simulator]. AB - A computer simulation of a Kidney-bladder model was prepared for automatic control of the urine concentration of antibacterial drug administrated. The following results were obtained in an investigation of the problems of complicated cystitis in vitro using ofloxacin. 1) It was suggested that the time required for elimination of the bacteria was prolonged as the level of complication of the disease state in the urinary tract increased. 2) In the model of highly complicated cystitis caused by urinary flow stagnation, recurrences were observed in vitro even with administration of a large dose of ofloxacin. 3) The time required for a elimination of bacteria tended to become shorter as the dose of the antibacterial agent increased. 4) The time until the start of regrowth of the bacteria tended to be prolonged as the dose of the antibacterial agent increased. 5) It was suggested by our in vitro experiment that if the background disease became more complicated, it would be more difficult to treat, as in the case of complicated cystitis. PMID- 2212762 TI - [Comparison of antibody titers to Chlamydia trachomatis in men and women]. AB - The titration of C. trachomatis antibodies (IgG, IgM and IgA) in sera obtained from antigen positive 220 men and 56 women, and antigen negative 384 men and 170 women was carried out by the method of microplate immunofluorescence antibody (MFA). Positive rates of the three class antibodies in antigen positive women were meaningfully higher than those in antigen positive men. Average IgG titer in antigen positive women was significantly higher than that in antigen positive men. Identical result was also obtained, when IgG titers were compared for sera collected from 93 couples. PMID- 2212761 TI - [Incidences of DIC complication in Japanese patients with malaria]. AB - Fourty eight patients with falciparum malaria (14) and vivax malaria (34) were evaluated retrospectively as to whether DIC (disseminated intravascular coagulation) had been complicated or not. Serum concentration of fibrin degradation products (FDP) was elevated in 8 cases (57%) of falciparum malaria and 3 cases (9%) of vivax malaria. Thrombocytopenia was found in 12 cases (88%) of falciparum malaria and in 30 cases (86%) of vivax malaria. Prothrombin time elongated in 4 cases (8%) and plasma concentration of fibrinogen decreased in 3 cases (17%). Only 4 patients, all of them were infected with falciparum malaria and all of three cases of cerebral malaria were included, met the criteria for the diagnosis of DIC complication and one case in vivax malaria suspected of the DIC. Abnormality grades in FDP concentration has closest association with DIC among the coagulation tests, therefore FDP test is indispensable for checking complication of DIC in malaria cases. The clinical profiles of 3 cases of cerebral malaria complicated with DIC are presented in this report. PMID- 2212763 TI - [Clinical and bacteriological studies in four cases of pulmonary infection caused by Protomonas extorquens]. AB - A novel bacterium, Protomonas extorquens was isolated from sputum, pleural effusion and ascitis in four cases of pulmonary infection by buffered charcoal yeast extract agar (B-CYE) which was generally used for Legionella spp. Three cases were so-called immunocompromised hosts (2 malignant diseases, 1 renal failure), and they died from underlying diseases. Protomonas extorquens was newly named by Komagata in 1984, which was characterized by production of pink pigment, growth in methanol medium and positive production of oxidase and catalase. This organism is ordinarily isolated from soil and dead leaves. This is the first report for isolation of P. extorquens from clinical specimens in Japan and it seems to have a significant role in immunocompromised hosts. PMID- 2212764 TI - [Passive protective activities of human sera against infection with strain ST67P of Staphylococcus hyicus]. AB - Five tenths ml of passive protective antibodies in 100 samples of normal human sera against challenge with an encapsulated strain ST67P of Staphylococcus hyicus in mice were examined. Thirty three of them passively protected in mice against infection with strain ST67P of S. hyicus. The activities were sensitive to 2 mercaptoethanol and were absorbed out either with rabbit anti-human IgG, IgM or IgA serum. Also, the serum activities were absorbed out with cell surface polysaccharide extracted from the cell surface substance of the strain. When passive protective human serum was absorbed out with cell surface polysaccharide, reduction of IgG, IgA and IgM contents were 14.48, 19.49 and 33.3 percent, respectively, while 2.17, 4, 55 and zero in non protective human serum. These results indicate that the protective activities against strain ST67P were specifically related to IgM globulin against the above cell surface polysaccharide. PMID- 2212765 TI - [Studies of intestinal microbial flora in the post-BMT (bone marrow transplantation) patients under a protected environment]. AB - The changes of microbial burdens of six patients with leukemia (four patients with acute leukemia; two patients with chronic leukemia) were studied before and after bone marrow transplantation (BMT) under protected isolation. Oral nonabsorbable and topical antibodies were administered prophylactically to all patients. Under a protected environment, genus and species number of intestinal microbial flora were not so decreased in all patients who were treated with antibiotics, but no episodes of severe septicemia were detected due to intestinal microbial flora. From many previous reports, the same pathogen was isolated from both blood culture and stool in the patients with septicemia, however, no septicemia developed in our cases in spite of residue of many intestinal bacteria. These data have demonstrated a significant advantage of treatment with protected isolation and intensive antibiotic prophylaxis through oral, topical and intravenous administration for severe infection prevention. PMID- 2212766 TI - [Microtiter enzyme-linked immunosorbent assay for diphtheria antitoxin in human sera--application of parallel line assay method]. AB - The antibodies against Diphtheria toxin in human sera were measured by the ELISA method and the antitoxin titer was calculated using the parallel line assay method which is a quantitative bioassay method. The reproducibility of this method and the comparison of the titer between this method and cell culture method were proven. The dose response curve of standard antiserum and test serum calculated by the parallel line assay method showed linearity, and the regression line of the test serum was parallel to the standard serum. The coefficients of variance (CV) of the antitoxin titers obtained from triplicate measurements of 3 serum samples ranged from 9.1 to 36.0%. The serum at low titer gave a higher CV level. A good correlation was observed between the Diphtheria antitoxin titer by the neutralizing test in cultured cells and that measured by ELISA by the parallel line assay method. The coefficient of regression was 0.996 and the coefficient of the correlation was 0.899. PMID- 2212767 TI - Immunological studies on soluble protective antigen (SPA) separated from culture supernatant fluids of Salmonella enteritidis. AB - Studies were carried out to analyze the antigenicity of Soluble Protective Antigen (SPA) separated from culture supernatant fluids of Salmonella enteritidis strain 2547. Mice injected with anti-SPA mouse serum were capable of tolerating a challenge dose of 100 LD50 S. enteritidis. After absorption of the anti-SPA mouse serum with lipopolysaccharide (LPS) prepared from strain 2547, no protective effect was observed. Ouchterlony immunodiffusion analysis showed that the P1 fraction obtained from Sephadex G-50 gel filtration of strain 2547 or 2822 LPS reacted with antiserum to SPA, but no reaction was observed with the P2 or P3 fraction. The LPS from strain 2547 gave 80% mouse protection against challenge with 100 LD50 of the homologous bacteria, while the P1 from strain 2547 LPS afforded 40% protective immunity. When P1, LPS and SPA were transferred into the footpad of SPA-immunized mice, a positive delayed footpad reaction was elicited. Similarly, macrophage migration inhibitory activity was observed when SPA-induced peritoneal exudate cells were cultured in medium containing P1, LPS and SPA. These results suggest that the antigenic determinant of SPA exists in the O antigenic components of LPS. PMID- 2212768 TI - [Studies on Chlamydia pneumoniae, strain TWAR infection. 2. Seroepidemiology of TWAR on healthy controls and patients with acute respiratory infections]. AB - To determine of Chlamydia pneumoniae, TWAR infection is common in Japan. The author performed a spot antibody prevalence study of adults and children living in Okayama prefecture. This study was carried out by microplate immunofluorescence antibody technique (MFA) using in situ inclusions of Chlamydia pneumoniae (TW-183), Chlamydia trachomatis (L2) and Chlamydia psittaci (Cal 10) as antigens respectively. And each chlamydial antiserum IgG, IgA, IgM titers were determined by the dilution and point for specific staining of the inclusions. The author studied people with and without evidence of acute respiratory infections, as determined by physical examination and medical history. 2050 sera of 1477 cases were collected from both groups between 1987 and 1989. The criteria for judgement the positivity of antibodies to chlamydia species are as follows: By comparing the IgG antibody titers determined with different chlamydia antigen, a case was regarded as having an antibody specific to a particular chlamydia species when the titer was highest for that strain and the titer was greater than x 64. In cases which blood was collected more than once, the point in time at which IgG showed the highest titer was used. TWAR specific antibody was detected to be 52/143 cases (36.4%) of healthy children (age 0-15) and 319/531 cases (60.1%) of healthy adults (age 16-85). It was also detected to be 134/478 cases (27.9%) of child patients with acute respiratory infections (age 0-15), and 231/325 cases (71.1%) of adult patients (age 16-95).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212769 TI - [Mixed type total anomalous pulmonary venous connection with the left upper pulmonary vein draining into the innominate vein and the other pulmonary veins into the coronary sinus--surgical correction in 2 infants]. AB - Surgical repair of the mixed type total anomalous pulmonary venous connection (TAPVC) in infancy is known to be difficult. In this report, experience of two infants with the mixed type TAPVC with the left upper pulmonary vein (PV) draining into the innominate vein and the other PVs into the coronary sinus (IIa + Ia (left upper PV) type TAPVC) is presented. In such cases, it has been said that the left upper PV should be left uncorrected, but we anastomosed the left upper PV, that was thin and fragile, to the left atrium and corrected all the other anomalous PVs. The results were satisfactory. Recently, Extra-Corporeal circulation, microsurgery, and other techniques have significantly progressed, so we consider that the anastomosis is possible in most infants with IIa + Ia (left upper PV) type TAPVC. In the future, careful clinical follow-up and repeat catheterizations should be done, and we'd like to examine the long term patency of the left upper PV. PMID- 2212770 TI - [Clinico-pathological study of primary malignant chest wall tumors]. AB - Clinicopathological studies of primary malignant chest wall tumor on 16 cases operated between 1962 and 1988 were made. Of 9 osteogenic sarcomas, 8 cases were chondrosarcoma and 1 case was Ewing's sarcoma. Of 7 soft part sarcomas, 2 cases were fibrosarcoma, liposarcoma and neurogenic sarcoma respectively, and one case was hemangiosarcoma. Most of the cases had symptoms, such as chest mass and/or chest pain comprehend symptoms for more than one year. The intrathoracic growth of tumor is common, especially in osteogenic sarcoma. The maximum size of tumor was 8.2 cm in a mean diameter. Preoperative histological diagnosis is difficult to make even though various radiologic diagnosis or pathological technique as biopsy or cytology were assessed. And true rate of preoperative diagnosis is limited only 43.8%. Wide resection combined with the tissue distant more than 3 cm length from tumor is recommended and 6 cases underwent combined resection of diaphragm, pericardium or lung. 3 cases underwent chest wall reconstruction using the Marlex mesh and 10 cases were able to direct closure, in 13 cases with ribs resection. The 5 year survival rate of endurable cases was 62.2%, and that of soft tissue sarcoma (68.6%) is better than that of osteogenic sarcoma (41.7%). The recurrent or metastatic rate in high, 7 cases (43.8%), but reoperation was added for 5 cases of local recurrence or for a case of lung metastasis. 5 year survival rate of cases with recurrence or metastases is relatively good, 46.8%, especially excellent in 4 cases with recurred lesions after more than 2 years of tumor free interval. PMID- 2212771 TI - [Surgical treatment of ischemic heart disease combined with hypothyroidism]. AB - Treatment for patients with ischemic heart disease and hypothyroidism contains many difficulties, such as a dilemma that thyroid hormone to hypothyroid patients may worsen angina. The purpose of this study is to propose an appropriate control of thyroid function in these patients before coronary artery bypass grafting (CABG), and to clarify the change of thyroid function during postoperative period. Because of progressive angina pectoris, five hypothyroidism patients underwent CABG. Preoperatively, minimal dose of L-Thyroxine (0-75 micrograms, daily) was administered orally to keep thyroid function at slightly low level before CABG. Ten consecutive CABG patients with normal thyroid function were selected as control group. Between both groups, there was no significant difference in age, coronary artery disease, and the number of bypass grafts. Serum T4, free-T4, T3, free-T3, and TSH were measured at 1st, 2nd, 3rd, and 7th P.O.D. In control group, pituitary-thyroid function was suppressed transiently. In hypothyroid group, T4 revealed no change and was kept at slightly low level during observed period. There was no significant difference in postoperative hemodynamics between both groups. Postoperatively all of hypothyroid patients got free from angina and received an adequate thyroid hormone replacement therapy without complications. It is concluded that CABG for patients with angina and hypothyroidism can be performed safely by keeping preoperative thyroid function at slightly low level. PMID- 2212772 TI - [Effective administration method of recombinant superoxide dismutase in acute myocardial ischemia and reperfusion]. AB - To determine the efficacy of direct versus systemic administration of human recombinant superoxide dismutase (rt-SOD) in acute myocardial ischemia and reperfusion, the following experimental model was applied. Twenty-one dogs were subjected to 30 minutes normothermic global ischemia caused by the occlusion of the ascending aorta followed by 60 minutes reperfusion. To eliminate collateral blood flows during the ischemia, bipulmonary hilus were cross clamped. The dogs were randomly assigned to three groups: group A (n = 7), 12 ml of normal saline was injected through the aortic root into the coronary artery 1 minute prior to reperfusion, in addition to a 30 minute continuous infusion of 50 ml of saline into the cardiopulmonary bypass circuit beginning just after reperfusion; group B (n = 7), rt-SOD (10,000 U/kg) dissolved in 12 ml saline was administered by bolus injection through the aortic root and an additional 30,000 U/kg of rt-SOD dissolved in 50 ml of saline was injected into the cardiopulmonary bypass circuit as the same manner as the group A; group C (n = 7), the treatment was similar to the group B except the bolus injection of rt-SOD was into the cardiopulmonary bypass circuit. The left ventricular stroke work index (LVSWI) was determined by a right heart bypass technique and expressed as a percent recovery of pre occlusion state. Morphologic structures were observed by the electron microscope. The coronary sinus blood was assessed for malondialdehyde (MDA) measured by TBA method and creatine phosphokinase (CPK). The percent of recovery of LVSWI after 60 minutes reperfusion was superior in group B (121 +/- 82%) than groups A (24 +/ 38%*, *p less than 0.05) and C (52 +/- 21%*). In group B, the myocardial cell structure had a normal appearance in most areas, but swollen mitochondria and disrupted myofibrils were observed in groups A and C. Serum MDA levels did not change in all groups. Increasing CPK levels after reperfusion were less in group b than group A. These results suggest that an adequate concentration of rt-SOD in the interstitial fluid or cell surface at the time of reperfusion may be required to prevent reperfusion injury. PMID- 2212774 TI - [Right ventricular dysfunction of mitral valve stenosis]. AB - Right ventricular function was studied in 9 patients with mitral valve stenosis who underwent mitral valve replacement (St. Jude Medical valve 29-31 mm) (MVR). The right ventricular systolic pressure/end-systolic volume index (RVSP/ESVI) correlated well with right ventricular ejection fraction (RVEF) in the normal control group thus it considered to be a index of right ventricular contractility. At rest, RVEF in the MVR group was significantly lower than that in the control group. However there was no difference in the RVSP/ESVI between both groups. In the MVR group, the total pulmonary resistance index (TPRI) and mean pulmonary arterial pressure (mPAP) were higher than those in the control group. During exercise, the RVSP/ESVI became higher in both groups, but RVEF did not increase in the MVR group. In the control group, RVEF became higher during exercise. In addition, TPRI and mPAP increased in the MVR group but the control group did not show significant changes during exercise. In conclusion, low RVEF after MVR, which reflects pump function of the right ventricle, was not caused by contractile dysfunction of the right ventricle but mainly by excess afterload due to irreversible pulmonary vascular resistance persisting after operation as a result of chronic pulmonary vascular hypertension. PMID- 2212773 TI - [Frozen blood from one closely related donor reduced complications of blood transfusion without adverse effects in the open-heart surgery]. AB - We used frozen blood from one closely related donor in 24 patients (group I) who underwent open heart surgery for congenital heart disease, in order to reduce of complications from a large quantity of blood transfusion. Blood of 600-2200 ml was collected from the single donor and was kept frozen until the operation. Two conditions of the patients were instituted, (1) body weight less than or equal to 40 kg (2) the single donor is father or mother or a close relative. The group of these patients was compared with patients using frozen autologous blood (group II) and patients using banked blood (group III). In group I patients two times of decline of red blood cell counts (RBC), hematocrit (Ht), hemoglobin (Hb) and total protein (TP) were noticed. The first was the period during the cardio pulmonary bypass. The second was the time about one week after the transfusion of frozen red cells. But degree of the decline was uneventful clinically. The increment of complications induced from the use of frozen red cells was not noticed, and there was no case of serum hepatitis in group I patients. We concluded that the open-heart surgery using frozen blood cells (single donor), if the application was appropriate, could be undergone safely and would be effective on reducing infection and reaction induced from blood transfusion. PMID- 2212775 TI - [Effect of controlled freezing-point storage of hearts--combined effect of controlled freezing-point storage and verapamil]. AB - Controlled Freezing-point Storage (CF Storage) is a new method of preserving foods in minus non-frozen temperature range. Therefore, the authors tried to apply this method to organ preservation. We investigated the effect of controlled freezing-point storage of hearts on ventricular function in isolated perfused rat heart (male, Sprague dawley strain, body weight about 300 g), and the combined effect of controlled freezing-point storage and Verapamil (0.5 mg/l). The hearts were perfused by working heart mode for 10 min, and received infusion of cardioplegic solution which was followed by 4 hours of cardiac arrest. The hearts were stored for 4 hours in Euro-Collins solution at 4 degrees C (4 degrees C group) and minus non-frozen temperature (CF storage group), and were stored for 4 hours in Euro-Collins solution containing Verapamil at minus non-frozen temperature (CF-Ve storage group). Then, the aerobic reperfusion by working heart mode was continued for an additional 30 min. The recovery rate of cardiac output was 33.5%, 62.5% and 74.2% respectively of the preischemic value in 4 degrees C group, CF storage group and CF-Ve storage group. The recovery rate of cardiac output in 4 degrees C group was significantly lower than that in CF storage group and CF-Ve storage group (p less than 0.01), and significant difference was noted between CF storage group and CF-Ve storage group (p less than 0.05). ATP activity after 4 hours of cardiac arrest was 13.9 micrograms/mg, 18.7 micrograms/mg and 18.3 micrograms/mg in 4 degrees C group, CF storage group and CF-Ve storage group respectively. ATP activity after 4 hours of cardiac arrest in 4 degrees C group was significantly lower than that in CF storage group and CF-Ve storage group (p less than 0.05). These data suggest that CF storage of hearts has a protective effect against an ischemic insult upon myocardial cell during hypothermic cardiac arrest, and the best metabolic and functional protection appeared when the hearts were stored in Euro-collins solution containing Verapamil at minus non-frozen temperature. PMID- 2212776 TI - [Shape change of erythrocyte induced by plasma during cardiopulmonary bypass for open-heart surgery]. AB - Effects of plasma of the blood under extracorporeal circulation (EC) on erythrocyte shape was determined on 14 patients undergoing open-heart surgery with cardiopulmonary bypass. Reversible echinocytosis was observed under an unfixed condition by mixing washed erythrocytes from normal volunteers with plasma of the patients' blood taken during EC. Either the plasma at the start or at the end of EC had no effect on echinocyte formation, while, the plasma obtained 2-3 hr after the onset of EC induced the most advanced stages of echinocytosis. Only the protein fraction after gel (sephadex G-25) filtration of the plasma induced the echinocytosis. Preheating the plasma at 56 degrees C for 30 min did not destroy the shape-transforming activity of the plasma. The plasma fatty acid/protein ratio was transiently increased with prolongation of EC and the ratio became maximum at 2-3 hr of EC, whereas the plasma cholesterol/protein ratio was kept constant during EC. Fatty acid content of the patients' erythrocytes was also increased accompanying the increase in plasma fatty acid/protein ratio. Therefore, it was suggested that the fatty acid incorporated from the patients' plasma into the cell membrane of the erythrocytes induced the echinocytosis. PMID- 2212777 TI - [Nonsurgical retrieval of intra-cardiovascular catheter fragments]. AB - Migrated intra-cardiovascular fragments from broken catheters were retrieved transvenously in 6 cases. In all of these cases, the catheters had been used for total parenteral nutrition. The catheter fragments were lodged in the pulmonary artery in 3 cases and in the right atrium in the others. A basket-type grasping forceps modified for this retrieval technique was inserted via the subclavian vein, femoral vein or basilic vein percutaneously. The migrated catheter fragments were removed successfully without any clinical complications in all 6 cases. Appropriate evaluation of the lodging site and length of the fragment, and careful examination of general condition should be carried out prior to this procedure. This noninvasive maneuver is simple, safe and reliable, and can be promptly. It is considered to be a reliable method of choice in cases of migrated catheter fragment. PMID- 2212778 TI - [Surgical treatment of constrictive pericarditis]. AB - Since 1957, 30 patients with constrictive pericarditis have been treated surgically in Kyushu University Hospital. The surgical approaches were the left anterolateral thoracotomy in 17 patients (group I); the median sternotomy without cardiopulmonary bypass (CPB) in 6 patients (group II); and the median sternotomy with CPB in 7 patients (group III). The hospital mortality was 3.3 percent. The mean postoperative follow-up period was 11.7 years (longest 30 years). The actuarial survival rate at 5 years postoperatively was 88% in total cases (100% in group I, 82% in group II and 52% in group III), 88% at 10 years, 75% at 15 years and 67% at 20 years. Several patients in group III, who underwent complete pericardiectomy using CPB showed severe congestive heart failure and arrhythmia postoperatively. The comparative study between an poor result group (patients who died within 10 years post-operatively) and a good result group (patients who survived more than 10 years postoperatively revealed that preoperative hepatomegaly, atrial fibrillation and the interval between the onset of symptoms and the pericardiectomy influenced the survival rate significantly. These results suggested that pericardiectomy using CPB was a safe method for removing the calcified pericardium in the patient with severe constrictive pericarditis. However, a careful long term follow-up was necessary for the patient with severe myocardial damage even though the complete pericardiectomy was performed. PMID- 2212779 TI - [Significance of fiberoptic bronchoscopy after pulmonary resection of lung cancer for early detection in second lung cancer]. AB - By the end of 1988, seventy five cases after pulmonary resection for lung cancer and one case after pulmonary resection for basal cell hyperplasia were examined with fiberoptic bronchoscopy as postoperative follow up. Endobronchial tumor was detected in 14 cases. In seven cases, endobronchial tumor was located at site far from the surgical bronchial anastomosis. These tumors were suspected as second lung cancer as long as examined by fiberoptic bronchoscopy. Histological type of all of these was squamous cell carcinoma. Re-operations were performed in five cases and two of them were early lung cancer. In 6 cases (13.6%) among 44 cases examined with fiberoptic bronchoscopy after pulmonary resection for central type squamous cell carcinoma, second lung cancer was detected. In the case of central type squamous cell carcinoma, usually the tumor appears to be of same histological type and at same location. Among those cases those who smoke heavily should be separated as high risk group. If this group is followed with fiberoptic bronchoscopy or sputum cytological examination, it is more possible to detect second lung cancer at an early stage. PMID- 2212780 TI - [In vitro hydrodynamic characteristics of heart valves in tricuspid position]. AB - At present there are many problems concerning the choice of heart valve for cardiac valve replacement in the tricuspid position. Thus, we devised an attachment head for the prosthetic valve in order to evaluate the hemodynamic characteristics of four clinically-available mechanical prosthetic valves and two xenografts in the pulsatile circulation system in the tricuspid position. Six artificial cardiac valves were used in this experiment; St. Jude Medical (SJM), Starr Edwards ball (S-E), monostrut Bjork Shiley (B-S), Omnicarbon, Carpentier Edwards (CE) supraannular, CE-pericardial whose tissue annulus diameter was 27 mm. The experimental instrument similar to that of Umezu et al, was prepared to determine the mean pressure gradient, output and calculated orifice area of each valve. Since many of the patients who must undergo tricuspid valve replacement have severe multi valvular diseases with atrial fibrillation, we experimented also under the condition of atrial fibrillation. At sinus rhythm under pulsation flow, no significant difference was shown in cardiac output between the various valves, but pressure gradient was higher with xenografts than with mechanical prostheses, and the SJM valve showed the widest efficient valve orifice area. The reduction rate of the efficient valve orifice area from sinus rhythm to atrial fibrillation was about 10% in the SJM valve, which was better rate than other heart valves. We observed significant differences in cardiac output, pressure gradient and efficient orifice area at sinus and atrial fibrillation rhythm. (p less than 0.01). PMID- 2212781 TI - [Aortic valve replacement in a patient with von Willebrand's disease--a case report]. AB - A 38-year-old man was admitted to our hospital with complaints of palpitation and shortness of breath. On auscultation, presence of severe aortic regurgitation was found. Seven years prior to admission, he had undergone rectal polypectomy complicated by postoperative serious hemorrhage which had led to the diagnosis of von Willebrand's disease. Aortic valve replacement with a Bjork-Shiley prosthesis was performed under routine cardio-pulmonary bypass. He received Confact-F as a replacement therapy of factor VIII throughout the perioperative period. His operative and postoperative courses were uneventful without difficulties in hemostasis. The patient was placed on a regimen of anticoagulation (Warfarin sodium) without increase in the bleeding tendency. He is asymptomatic and doing well six months after the operation. PMID- 2212782 TI - [A case report of Ebstein's anomaly treated with Carpentier's procedure]. AB - A 42-year-old male patient was admitted with congestive heart failure. Echocardiogram and cardiac angiogram revealed Ebstein's anomaly and severe tricuspid valve incompetence. He underwent Carpentier's procedure for the treatment of Ebstein's anomaly. Carpentier's procedure consists of the following two new points; (1) the right atrium and atrialized ventricle is plicated longitudinally; (2) the anterior leaflet and the posterior leaflet of tricuspid valve are transposed with a clockwise rotation to the level of the normal tricuspid anulus. Compared with Hardy's procedure (transverse plication), longitudinal plication preserves the cavity and the function of the right ventricle and excludes atrialized chamber. In our case, there is a trivial residual regurgitation of tricuspid valve postoperatively, but the patient's clinical status has improved remarkably. We conclude that Carpentier's procedure is an effective operation for Ebstein's anomaly. PMID- 2212783 TI - [A case of pulmonary arteriovenous fistula treated by subsegmentectomy with CUSA]. AB - A 35-year-old female who had no symptom was admitted to our hospital because of an abnormal shadow in the middle area of the right lung in a chest X-ray film. The chest tomography, CT and the angiography revealed a pulmonary arteriovenous fistula. It located in the right upper lobe, and was successfully resected by subsegmentectomy of S3b using CUSA. The results indicated that the CUSA was useful in the surgical treatment of the pulmonary arteriovenous fistula which had many vascular anastomoses. PMID- 2212784 TI - [Two cases of pulmonary leiomyosarcoma]. AB - Pulmonary sarcoma is a rare tumor of the lung. There are 81 cases in the literature for review, including our two cases. Our first case who was a thirty seven year old male who was admitted to our hospital with complaints of left back pain. His chest X-ray showed an 11 X 14 cm tumor shadow in the lower left lung area. A left upper lobectomy was performed, and the histological diagnosis was leiomyosarcoma of the pulmonary vein. He died due to mediastinal recurrence 29 months later. Our other case was a fifty-six year old female. Her chest X-ray showed an abnormal shadow that was a tumor shadow in the right central lung area of 4 cm in diameter. As the diagnosis of the transcutaneous lung biopsy was benign tumor, partial resection of lung was performed. The histological diagnosis was leiomyosarcoma of the bronchus, and she is alive and well at 29 months after the operation. As the rate of diagnosis in leiomyosarcoma detected by transcutaneous lung biopsy is low, the most acceptable method of diagnosis is a total examination, including cytology of sputum, bronchoscopic findings, and roentgenoscopy. Probe thoracotomy would also be necessary if malignancy could not ruled out. The treatment of lobectomy should include lymph node resection. PMID- 2212785 TI - [Right ventricular outflow tract reconstruction in two neonates with pulmonary atresia and intact ventricular septum]. AB - Two neonates, aged 8 and 18 days, with pulmonary atresia and intact ventricular septum underwent right ventricular outflow tract reconstruction with an autologous pericardial transannular patch. Preoperative cardiac catheterization revealed a tripartite right ventricular morphology with suprasystemic right ventricular morphology with suprasystemic right ventricular systolic pressure (right ventricular to left ventricular peak pressure ratio was 1.2 in case 1 and 2.0 in case 2). Right ventricular volume was 73.5% of normal and 115% of normal respectively. Generous resection of the infundibular myocardium was done and a patch was inserted with the heart kept beating as the perfusate temperature of 32 degrees C. In case 1 a modified Blalock-Taussig shunt was added on the postoperative day 21, because of the insufficient growth of the right ventricle, but in case 2 prostaglandin E1 could be discontinued on the postoperative day 9. PMID- 2212786 TI - [Thoracic duct cyst--a case report]. AB - A case of thoracic duct cyst was reported. The patient, 72 year old man, was admitted with chief complaint of dysphagia. Chest X-ray film demonstrated an ovoid mass at the right upper mediastinum and the esophagus pressed by the tumor to the right. CT scan showed a round tumor with obscure margin located at the right upper mediastinum. Other laboratory data were almost within normal limits. Thoracotomy was performed on March 26, 1987 under diagnosis of leiomyoma of the esophagus. A fluid containing cyst covered with pleura was found at the upper mediastinum. The tumor was connected to the thoracic duct at its upper and lower portion. The cyst was isolated by sharp and blunt dissection without difficulties and removed. The cyst measured 7.5 X 4.5 X 4.5 cm and contained chyle. Pathological examination revealed no evidence of malignancy. Postoperative course of this patient was uneventful, and dysphagia was disappeared. PMID- 2212787 TI - [A case of thymic carcinoma]. AB - A 41-year-old male visited with chief complaints of chest pain and cough. The patient was operated on under a diagnosis of invasive thymoma. The tumor was located in the left lobe of the thymus and measured 6 X 9 cm. Since the tumor invaded the left innominate vein, pericardium, and the upper lobe of the left lung, we resected it with adjacent structures. Postoperative pathological examination indicated squamous cell carcinoma of the thymus. Because the tumor metastasized also to the mediastinal lymph nodes, the patient was treated postoperatively by radiation therapy and adjuvant chemotherapy mainly with CDDP. The patient is well presently 2 years after operation without signs of recurrence. PMID- 2212788 TI - [A right atrial thrombus after Fontan procedure--a case report]. AB - A 17-year-old male with tricuspid atresia who underwent a modified Fontan procedure died due to heart failure 4 years and 6 months after operation. At autopsy a thrombus was found in the right atrial appendage. From the experience, it might be recommended to excise the appendage when the modified Fontan procedure leaving the appendage was employed. In addition, anticoagulation therapy as well as regular echocardiographic examination for detecting thrombus formation should be considered after the operation. PMID- 2212789 TI - [A two-year-old child with tracheal stenosis due to tracheostomy treated by end to-end anastomosis of the trachea]. AB - Successful operation performed on a 2-year-old boy with tracheal stenosis due to long-term intubation was reported. He was admitted to our department 1 year after a neurosurgical operation. Endoscopically, destruction of cartilage rings was observed just above the site of tracheostomy, and the tracheal wall was collapsed without a help of tracheal tube. Reconstruction of the trachea by circumferential resection and end-to-end anastomosis was done. During the operation, the patient was uniformly ventilated by tracheal tube through nasal intubation. After the operation, tracheal intubation was continued for 7 days, and anterior fixation of neck for 8 days. The postoperative course was uneventful and the patient remains asymptomatic 8 months after operation. PMID- 2212790 TI - [A successful surgical case of DeBakey IIIb dissecting aortic aneurysm in association with right aortic arch]. AB - A case of chronic DeBakey IIIb dissecting aneurysm in association with right aortic arch is reported. A 49-year-old man having encountered an aortic dissecting episode two years ago, was examined more closely because the aneurysm became larger recently. Digital subtraction angiography (intra-venous and intra aortic) showed DeBakey IIIb dissecting aneurysm associated with a right aortic arch with aberrant subclavian artery. The entry of the aneurysm was in the right descending aorta passing from left thorax to right. The operative indication was for enlarged false lumen in this case. Graft replacement of the aneurysm and closure of the false lumen in the right thorax was performed under partial cardiopulmonary bypass through right thoracotomy. Postoperative digital subtraction angiography showed that dissection was in the abdominal aorta but false lumen in the thorax was completely closed. The patient has made a comeback working. A case of dissecting aortic aneurysm associated with right aortic arch is extremely rare. To our knowledge, this is the third such case reported in Japan, but the first case of a successful graft replacement for dissecting aortic aneurysm associated with right aortic arch. PMID- 2212791 TI - [Report of a case which survived rupture in a hepatic artery mycotic aneurysm after aortic valve replacement]. AB - A case in which rupture of a hepatic artery aneurysm occurred 4 months after aortic valve replacement because of aortic regurgitation due to infective endocarditis (IE) is reported. The patient was a 41-year-old male who underwent aortic valve replacement and closure of an abscess cavity of the Valsalva's sinus because of aortic regurgitation and an abscess of the Valsalva's sinus complicated with active IE. His postoperative course was good with no fever. Four months postoperatively, rupture of an aneurysm of the left intrahepatic artery occurred suddenly, and the patient's life was saved by resection of the lateral segment of the left lobe of the liver. Histologically, the wall structure of the aneurysm was not preserved, infiltration of neutrophils was seen in part of the wall, and a mycotic aneurysm of the left hepatic artery within the liver cause by IE was diagnosed. In Japan, only four cases, including the present one, of mycotic aneurysm of the hepatic artery have been reported in the literature examined, and this was the first case in which the patient's life as saved after a rupture. It is essential when observing the course of IE patients to bear in mind at all times that such a complication might occur. PMID- 2212792 TI - [43rd meeting of the Japanese Association for Thoracic Surgery. Tokyo, 18-20 October 1990. Abstracts]. PMID- 2212793 TI - Planning a medical congress. PMID- 2212794 TI - Red blood cell aggregation in diabetes mellitus. AB - The aim of this work is to study the red blood cell aggregation in diabetic patients. Investigations have been performed via rheometric technics on four various types of diabetics (diabetics with good metabolic control, diabetics with poor metabolic control, diabetics with a distal angiopathy, without clinical signs, diabetics with a distal angiopathy characterized by cutaneous trophic disorders). Results, compared with those of healthy subjects, show that the reversible phenomenon of erythrocyte aggregation is significantly modified in diabetic. Indeed, the red cell aggregation tendency is found to be increased in diabetics. This hyperaggregation becomes more important when the diabetes is characterized by a poor metabolic control or a distal angiopathy with or without cutaneous trophic disorders. Disturbances of red cell aggregation observed in this report are discussed as a result of plasma protein changes and may confirm the role of hemorheological properties in the pathogenesis of diabetic angiopathy. PMID- 2212795 TI - Epidemiology of risk factors of atherosclerosis and preventive program for youth. AB - In 2208 boys aged 15 to 22 years the incidence of risk factors of atherosclerosis were determined. The risk factors were found in 33.7% of boys. The level of risk factors in youth has increased with age (p = 0.001), especially hypertension (p = 0.001) and smoking (p = 0.001). The authors concluded that the most important methods of prevention of atherosclerosis in youth should be: identification of high-risk individuals (overweight, hypertension, hyperlipidemia, family history of CHD and PAD, ischemic postexercise ST segment depression), health education and motivation for change, modification nutritional habits in cases of hyperlipidemia and overweight (prevention of early atherosclerotic lesions in childhood), early diagnosis and control of hypertension, practice of low salt intake, avoidance of smoking, sufficient physical activity (prevention of atherosclerotic disease mainly in adulthood). PMID- 2212797 TI - Improvement of VEP photostress recovery test in patients with stenosis of the carotid artery and thrombosis of the internal contralateral carotid, after endarterectomy. AB - Nine patients with carotid stenosis and thrombosis of the internal contralateral carotid were examined by means pattern VEP (visual evoked potential) after photostress to evaluate if the disobliteration of the stenotic side may determine an increase in the overall blood supply to the brain. Our results permit to detect the increase of collateral blood flow to both hemisphere after carotid endarterectomy. PMID- 2212796 TI - The effect of enalapril on leg muscle blood flow in patients with claudication. AB - In the percent study the authors have demonstrated that the peripheral blood flow and resistance as measured by strain-gauge venous occlusion plethysmography were favourably altered by enalapril. The peripheral blood flow increased significantly and since there was no detectable change in ankle pressure this indicated a decrease in resistance during administration of the drug. PMID- 2212798 TI - Doppler ultrasound in assessing systolic left ventricular function in cardiovascular patients. AB - Determination of left ventricular (LV) function is of vital importance in cardiovascular medicine and surgery. Various methods have been introduced to achieve this goal but a noninvasive method is more appropriate as it could be used during exercise to follow-up patients and study the response to medical or surgical intervention. The Doppler ultrasound technique of transcutaneous aortovelography (TAV) has been introduced as a successful approach using a 2 MHz transducer to measure the aortic blood velocity in the aortic arch. From the Doppler ultrasound signals the systolic velocity integral is derived (Sd; the stroke distance which is an index of stroke volume) and its percentage change at maximal-tolerated supine exercise (% delta Sd). The latter was found to be a function of LV ejection fraction and thus proved to be a useful approach to assess LV function in patients with coronary artery disease. Using TAV it was found that coronary artery bypass grafting improves LV function during exercise (rather than at rest) irrespective of the presence of a history of myocardial infarction prior to the operation. In patients with intermittent claudication assessment of LV function proved of great use. The % delta Sd was significantly lower in claudicants with positive stress ECG tests than those with negative test. There was a linear correlation (r = 0.51) between the % delta Sd and the percentage change in the ankle/brachial systolic blood pressure index in response to standard 1 minute of exercise. Assessment of LV function in cardiovascular patients is thus of great clinical importance and provides more insight into the mechanism of the disease and assess the response to management. PMID- 2212799 TI - The influence of hemodilution on left ventricular function. AB - In nine anesthetized mongrel dogs anemia was produced by exchanging blood with plasma substitute thus reducing hemoglobin gradually in three steps. Aortic, atrial and ventricular blood pressures, cardiac output, electrocardiogram, phonocardiogram and the first derivative of the left ventricular pressure were continuously monitored. Blood samples were taken to determine hemoglobin, blood gases and whole blood viscosity. Progressive hemodilution resulted in a significant increase in cardiac output and left ventricular stroke work, while total peripheral resistance, oxygen content and whole blood viscosity decreased significantly. There were no significant changes in cardiac pressures, myocardial contractility, diastolic pressure time index and blood gases. The oxygen supply/demand ratio had gradually declined, while electrocardiogram showed no significant changes. These results suggest that moderate isovolemic hemodilution in animals with normal coronary vessels does not impair left ventricular function as this was manifested by the unchanged hemodynamic and electrocardiographic findings. PMID- 2212800 TI - Panarterial ultrasonography. A non invasive evaluation of the peripheral arterial system. AB - Based on the concept of the generalized character of atherosclerosis which tends to assume characteristic patterns that may be classified by a predominant site of distribution of the disease within five major categories according to DeBakey, we have developed the examination of the whole arterial system, except the coronary arteries, by using ultrasonic technics which have coined panarterial ultrasonography (PU). This includes a series of ultrasonic examinations by using the Doppler ultrasonic and B-mode duplex or triplex scan apparatus with various probes for the detection of arterial flow and imaging of the various arterial segments. During the last years 716 patients were submitted to PU. The indications for and the findings resulting from the application of PU are presented. PMID- 2212801 TI - Color flow Doppler in the evaluation of aortic aneurysms. AB - Fifteen patients with aortic aneurysms have been evaluated with Doppler color flow imaging. Two distinct flow patterns are noted: a smooth laminar pattern and a turbulent circuitous pattern. It is postulated that those patients with a turbulent pattern may be at greater risk for aneurysm enlargement and rupture. PMID- 2212802 TI - [Transition of ovarian arterial compliance during the human menstrual cycle, assessed by Doppler ultrasound--correlation with serum hormone levels]. AB - Ovarian arterial velocimetry was performed using color and pulsed Doppler ultrasound. Seventy-one examinations were done on 9 healthy women with regular menstrual cycles. The change in ovarian arterial compliance was based on the calculation of the pulsatility index (PI). In the active ovary carrying a dominant follicle or corpus luteum, PI in the early proliferative phase was significantly higher than that in the late proliferative phase (p less than 0.001), and PI in the early secretory phase was significantly lower than that in the late proliferative phase (p less than 0.001). PI became significantly higher in the late secretory phase than that in the early secretory phase (p less than 0.001). In the inactive ovary without a follicle of corpus luteum, no changes were seen among the values for PI, in any menstrual phase. There was a significant difference between the values for PI in the active ovary and the inactive ovary in the late proliferative, the early and the late secretory phases (p less than 0.001), respectively. The PI values for the active ovary significantly correlated with the serum progesterone levels (r = -0.53, p less than 0.05) but not with the estradiol levels. These findings provide a useful foundation for assessing ovarian hemodynamics during the menstrual cycle. PMID- 2212803 TI - [The mechanism of cytotoxicity of monoclonal antibodies to gynecological cancer cell-lines]. AB - The cytotoxicity including complement dependent cytotoxicity (CDC) and antibody dependent cell-mediated cytotoxicity (ADCC) of two kinds of monoclonal antibodies (Mo-Ab), namely, MSN-1 which was obtained by means of an immunization procedure with intact SNG-II cells from human endometrial adenocarcinoma and HMST-1 obtained from hybridoma fused lymphocytes from lymph node with murine myeloma cells were studied by the 51Cr liberation test in vitro. 1) Against SNG-II, MSN-1 and HMST-1 showed significant CDC activity at 38.4 +/- 4.2% and 41.9 +/- 4.8% respectively, when a guinea pig complement was used. However, no significant CDC, action on SKG-IIIb was induced by MSN-1 or HMST-1. 2) Mo-Ab:MSN-1 and HMST-1 showed no significant liberation of 51Cr in relation to SKG-IIIb and SNG-II when using peripheral blood lymphocyte (PBL) separated by centrifugation gradient as the effector cells, and then the cytotoxicity of PBL alone against K-562 cell, SNG-II and SKG-IIIb was 40%, 9% and 2% respectively. This suggested that neither Mo-Ab had any ADCC activity and that SKG-IIIb and SNG-II cells were NK resistant cell-lines. PMID- 2212804 TI - [Effect of danazol on bone mineral content and bone metabolism in patients with endometriosis]. AB - Danazol, which is commonly employed in the treatment of endometriosis creates a low estrogen and high androgen condition by suppressing ovarian steroidogenesis. When a reproductive-aged woman suddenly develops low estrogen, even if it is reversible, it is possible that it can have some effect on her bone mineral content and there is the danger that this might constitute a risk factor in the development of postmenopausal bone metabolism. In 12 cases of endometriosis (average age 42.2) 400 mg/day Danazol was given for 4 months to determine if a low estrogen and high androgen condition actually continued. The effect on the bone metabolism which provides a background to metacarpal bone mineral content was also examined in comparison with before and after seven months' administration. As a result, after Danazol administration, estradiol showed a tendency to decrease and dehydroepiandrosterone showed a tendency to increase although no significant change in the estrogen and androgen level was recognized. There was also no change on the bone mineral content and there was no significant change in bone metabolism, calcitonin excepted. Therefore, from the results of calcitonin evaluation, 400mg/day Danazol administered for 4 months does not seem to be absorbed by bone and at least appears not to have any significance as a bone metabolism risk factor. PMID- 2212805 TI - [Immunohistochemical studies of the localization of prolactin in human term decidua]. AB - Human amniotic fluid possesses a considerably higher concentration of PRL. And it is generally accepted that decidual cells are the source of amniotic PRL and, decidual PRL transfers into amniotic fluid across the fetal membranes. Because few studies on the fine morphological structure of decidual tissue have been reported, with the aid of electron microscopy, we noted the number of secretory granules in the partial decidual cells which were obtained at spontaneous term vaginal delivery. 1 Using immunohistochemical procedures and the PAP complex method, immunized anti-PRL revealed PRL reactivity on the numerous granules or globules. 2 Incubation for acid phosphatase (AcP-ase) activity was done after the tissues were fixed. The medium used was Gomori lead medium, with glycerophosphate as substrate. Lysosomes are present in decidual cells. In lysosomes, numerous residual bodies with reaction product are evident as electro-opaque black bodies. 3 In staining of tissues for the study of lipid granules, Sudan III solution (Sudan Schwarz B dissolved in 70% alcohol) was used. Decidual cells contain fewer and bigger cytosolic lipid spheres. PMID- 2212806 TI - [Study on prognosis of threatened abortion assessed by multivariate analysis]. AB - The serum concentrations of various hormones which included hPL, progesterone(P), estradiol(E2) and 17 alpha-hydroxyprogesterone (17P) in serum, and hCG in urine were measured simultaneously in patients with threatened abortion to evaluate the prognosis. Ultrasound scanning was also undertaken. One hundred and thirty-six patients at 5 to 8 weeks of gestation were divided into two groups retrospectively. Group A consisted of 99 patients with a good prognosis and group B consisted of 37 patients who aborted spontaneously. The mean concentrations of hormones, and ultrasound findings (GS, CRL and FHM) were not significantly different in both groups at 5 weeks. An attempt was made to apply the data to the computation in multivariate analysis. By discriminant analysis, 100% reliability was achieved in separating the two groups according to hormone levels only at this stage of pregnancy. At 6 weeks, the hCG, P and E2 values were statistically higher in group A than B. Because of the overlapping of the data, principal component analysis was attempted. Two groups were roughly separated. The values for factor loading indicated that GS, CRL and 17P effective in making the separation possible. At 7 and 8 weeks of gestation, the mean concentrations of hCG, hPL, P and E2 were significantly higher in A than B. The factor loading values indicated that ultrasound findings were essential in separating into two groups. These results suggested that hormonal analysis may be useful in assessing the prognosis in threatened abortion in the early stage of gestation (5 and 6 weeks), while ultrasound findings make an accurate prediction for the prognosis possible after 7 weeks of gestation. PMID- 2212807 TI - [Alteration of prostaglandin I2 on ripening in rabbit uterine cervix]. AB - We have attempted to clarify the relationship between PG synthesis and ripening in rabbit uterine cervix. In this paper, I examined whether PGI2 release from endogenous arachidonic acid is changed in ripening in the uterine cervix. The release of 6-keto PGF1 alpha significantly increased after the 20th day of gestation and at term reached its maximum, which was about six times that of non pregnant rabbits. I then measured the activity of phospholipase A2 in the tissue and found that it was significantly increased during gestation. Furthermore, to determine which cells synthesize PGI2, several kinds of cells from the uterine cervix of non-pregnant and pregnant rabbits were isolated and cultured. Among these cells, smooth muscle cells were shown to have the PGI2 synthesizing activity. The rate of conversion of arachidonic acid to PGI2 in the cell was about 30%, and that to PGE2 was negligible. To examine the change in PGI2 synthesis with gestational age, cells from both non-pregnant and from the 25th day of gestation were cultured and the release of PGI2 from these cells was determined by radioimmunoassay of 6-keto PGF1 alpha. The release of 6-keto PGF1 alpha in gestation was about three times as high as in the cells from non pregnant rabbits. PMID- 2212808 TI - [Prevention of vitamin K deficiency in the early neonatal period--prophylactic oral administration of VK to the mother]. AB - We studied the effect of vitamin K(MK-4) on the prevention of vitamin K deficiency in the early neonatal period. MK-4 (20 mg/day) was given orally for 1 7 days to 183 pregnant women at 37-39 weeks gestation. In the MK-4 treated group, there were no cases of melena neonatorum but there were 9 cases in the untreated group (9/757, 1.2%). To investigate the influence of MK-4 administration on liver function and the VK dependent coagulation system, maternal and umbilical venous blood were taken to measure T-Bil, GOT, GPT, gamma-GTP, LDH, and II, VII, X activity and HPT. There was no significant difference between these values in MK treated and untreated groups. MK-4 concentrations were measured in the maternal and umbilical venous blood of 68 subjects. The level of MK-4 in umbilical venous blood was less than 0.1 ng/ml in 17 of 21 subjects not treated with MK-4 but it was over 0.1 ng/ml in 30 of 47 MK-4 treated subjects. However, no MK-4 was detected in 6 of 8 subjects who were treated for 1 day. The level of MK-4 in maternal blood was less than 0.1 ng/ml in 12 of 21 untreated subjects but it was 0.19-92.6 ng/ml in all of the 47 MK-4 treated subjects. The mean MK-4 concentration in cord blood as a percentage of that in maternal blood was 17.9%. These findings indicate that MK-4 is effectively transported from maternal to fetal blood through the placenta and its administration to pregnant women is useful in preventing melena neonatorum. PMID- 2212809 TI - [Clinical application of magnetic resonance imaging (MRI) in uterine disease]. AB - We investigated the value of MRI in investigating uterine anatomy and disease. 1. Normal uterus: The signal intensity and endometrial thickness changed during the menstrual cycle. Endometrial thickness in the secretory phase was 12.8 +/- 3.6 mm, significantly greater than in the proliferative phase (5.4 +/- 0.7 mm, p less than 0.01). In contrast, endometrial thickness was reduced in postmenopausal women (4.1 +/- 0.9 mm) and was never over 6 mm. 2. Uterine disease: a. T2 weighted images were useful in differentiating leiomyoma and adenomyosis. Leiomyomas appeared as well-circumscribed nodules with sharp margins, while adenomyosis was seen as a low signal intensity area with an irregular border extending beneath the endometrium. b. In endometrial carcinoma, endometrial thickening with a high signal intensity was a characteristic of T2-weighted images, the maximal thickness being 16.5 +/- 6.9 mm. Moreover, endometrial carcinomas invading over 1/3 of the myometrium showed the following features: (1) The ratio of maximal endometrial thickness to uterine cross sectional diameter was over 50%. (2) The minimal myometrial thickness was under 5.0 mm. (3) The minimal to maximal myometrial thickness ratio was under 50%. Furthermore, cervical extension could be detected in all cases of endometrial carcinoma extending to the myometrium in T2-weighted images. PMID- 2212810 TI - [Study on the specific diagnosis of meconium aspiration syndrome (MAS) with fluorometry]. AB - Porphyrins are found in fetal urine, neonatal urine, amniotic fluid, and meconium. Zn-coproporphyrin (Zn-CP), which we identified in meconium, has two fluorescent peaks at 580 nm and 630 nm, and Coproporphyrin (CP), found in fetal urine, has one fluorescent peak at 620 nm, when both porphyrins are excited at 405 nm. In this study, the fluorescent peak at 580 nm was used to detect Zn-CP in neonatal urine, using the new index, that is the Urinary Fluorescence Meconium Index (UFMI); UFMI = F580-(F580 + F600)/2 [F: fluorescence intensity]. We obtained urine samples from neonates in these three groups: Group-I: Meconium Aspiration Syndrome (MAS; n = 3), Group-II: non-MAS with meconium stained amniotic fluid at delivery (n = 18), and Group-III: non-MAS with clear amniotic fluid at delivery (n = 25). The UMI (Urinary Meconium Index) was also measured by conventional optical absorbance. The results show that many false positive cases were observed in UMI, and that no false positive cases were observed in UFMI. These results lead one to speculate that Zn-CP, which is specific in meconium, is used in UFMI measurement, while UMI measurement by absorbance cannot exclude contamination by CP in neonatal urine, so Zn-CP and CP are measured all together. UFMI values reflected the clinical course of neonates. It is concluded that UFMI is a more sensitive method than UMI for the diagnosis of MAS. PMID- 2212811 TI - [Lumbar bone density and serum osteocalcin in pre- and postmenopausal women]. AB - The bone mineral density of the lumbar spine (L3) and serum osteocalcin (OC) were measured in 31 pre- and 25 postmenopausal women. Bone density was measured by single energy quantitative computed tomography (QCT value). A significant inverse correlation between the QCT value and age was demonstrated in postmenopausal women but no correlation was found in premenopausal women. Mean QCT value was significantly lower in postmenopausal women than in premenopausal women. Serum OC increases with advancing age and mean serum OC was significantly higher in postmenopausal women than in premenopausal women. A significant inverse correlation between the QCT value and serum OC was demonstrated. These data suggest that there is an association between menopause and accelerated loss of lumbar bone density and that the serum OC level may be useful in evaluating the bone mass. PMID- 2212812 TI - Immunoregulatory activity in human decidua. AB - The immunoregulatory factor(s) that suppresses normal human peripheral blood mononuclear cells (PBM) function was extracted from the decidua of pregnant women (8-13 weeks). Compared with extracts from the proliferative endometrium, the decidual extracts from fresh surgical specimens markedly inhibited 3H-thymidine incorporation by PBM in response to T-cell mitogens. The majority of the lymphocyte-inhibitory activity was found to be associated with a material of large molecular weight in the decidua, as estimated by Sephadex G-200 filtration. Immunoelectrophoretic analysis followed by Sepharose 4B-anti-human IgG affinity chromatography of the fraction having the inhibitory activity revealed the causative factor to be most likely IgG or a substance copurified with IgG. The results are discussed with respect to a possible role of IgG in a localized non specific suppressor mechanism in the decidua preventing maternal immunologic attack on the fetal allograft. PMID- 2212813 TI - A case-control study of uterine endometrial cancer in Japanese and Finn. AB - The difference between the endometrial cancer incidence in Japanese and Finnish women (lower and higher incidence, respectively), was evaluated on the basis of data from cases of endometrial cancer, cervical cancer and benign gynecological disease in both countries. The comparison took into account the various personal and clinical characteristics of these cases. In endometrial cancer, Japanese and Finnish women had similar characteristics except for the age at first delivery, the age at last delivery and obesity. However, obesity in postmenopausal women in the two countries was similar. Common factors in the two countries included few pregnancies and deliveries, nullipara and single women. In cervical cancer, no difference between the characteristics of Japanese and Finnish women was found except that Japanese women had a higher frequency of pregnancy. In benign diseases, characteristics were similar to those of endometrial cancer in Finnish women, but this was not the case in Japanese women. These facts may indicate the number of Finnish women with endometrial cancer risk factors is greater than the number of Japanese women with these risk factors. This was thought to account for the difference in the incidence of endometrial cancer. PMID- 2212815 TI - [Treatment of habitual abortion by the mixture of paternal leukocytes and OK 432]. PMID- 2212814 TI - [The management of pregnancy complicating idiopathic thrombocytopenic purpura by fetal blood sampling]. PMID- 2212816 TI - [Successful transvaginal delivery with cordocentesis in a case of idiopathic thrombocytopenic purpura]. PMID- 2212817 TI - [A case report of adenocarcinoma arising from the rectovaginal septum and its liver metastasis]. PMID- 2212819 TI - [Cytofluorometric nuclear DNA analysis and immunohistochemical study on the proliferative activity of the trophoblasts in human early gestation]. AB - Changes in proliferative activity in trophoblastic cells were evaluated in various different sites of implantation. DNA content analysis by cytofluorometry and immunohistochemical study using a monoclonal antibody Ki-67 was performed in 5 cases with a gestation period of 8-9 weeks. The measurement of proliferative activity of trophoblastic cells was analysed in four different sites of implantation: (1) the top of the anchoring villi, (2) the cell column, (3) the intermediate trophoblasts in the decidua basalis and myometrium, and (4) the free villi. A large number of Langhans cells on the top of the anchoring villi (L cells) were mononuclear and tetraploid. It was demonstrated that the L-cell group had 2C, 4C and 8C peaks and also had a 4C mode. S-phase fraction was also found in the L-cell group. The so-called intermediate trophoblasts (IMT) in the cell column, decidua basalis and myometrium had 2C and 4C peaks and no S-phase fraction. Ki-67 positive cells existed only in the L-cell group. The findings are as follows: 1. The L-cell group had a higher proliferative activity than the other trophoblasts. It was found to have a mononuclear tetraploidy pattern. 2. It is suspected that the cells having 4C DNA content in the IMT originated in the L cell group. 3. In conclusion, L-cells may differentiate to syncytial trophoblasts and IMT. PMID- 2212818 TI - [An in vitro study on the mechanism of CA125 production of endometrial cells- comparison of eutopic and heterotopic endometrium]. AB - Human eutopic and heterotopic endometrium were cultured and epithelial cells were isolated from stromal cells by the modified method of Satyaswaroop et al. in order to investigate the cause of elevated serum CA125 levels in patients with adenomyosis. Flow cytometry (FCM) was used to analyze the relationship between cell cycle and CA125 production. 1. Microscopically, epithelial cells showed a tadpole-like appearance, while stromal cells were spindle-shaped. However, morphologically, no difference could be found between eutopic and heterotopic endometrial cells. 2. Immunocytochemical techniques (indirect enzyme immunoassay and fluorescence method) have demonstrated the presence of CA125 both on the cell membrane and in the cytoplasm of eutopic and heterotopic epithelial cells. Stromal cells were weakly stained by the fluorescence method, but not by enzyme immunoassay. 3. Double staining of CA125 and DNA was performed and analysed with FCM. Heterotopic epithelial cells produced a significantly higher amount (16 times higher) of CA125 than the eutopic epithelial cells. Stromal cells produced a small amount of CA125. These findings suggest that the elevation of serum CA125 levels in patients with adenomyosis may be due to greatly increased production of CA125 by heterotopic epithelial cells, in addition to the production of CA125 by eutopic ones. PMID- 2212820 TI - [Ultrasonographical study on luteinized unruptured follicle]. AB - The clinical features and the intrafollicular environment of luteinized unruptured follicle (LUF) were investigated in 60 infertile women by means of ultrasonography. LUF was diagnosed in daily ultrasound scans in 52 (13.5%) of 384 apparently ovulatory cycles. High incidences of LUF cycle were observed in the patients with polycystic ovary (37.5%), endometriosis (24.7%) and a history of pelvic surgery (26.2%), whereas LUF cycles were rare in the patients who conceived (2.7%). Mean follicular diameter measured by transvaginal ultrasonography showed no difference between LUF and ovulatory cycles during the follicular phase, whereas during the luteal phase, a continual growth pattern without follicular collapse was observed in LUF cycles. The ultrasonic aspiration of the follicle was carried out in 21 LUF cycles on the luteal phase. In 19 cases, hormonal profiles for the aspirated follicular fluid coincided with the preoperative diagnosis, and in 6 of 19 cases (31.6%), the presence of entrapped oocytes, direct evidence of LUF, was demonstrated. The morphological observation revealed that the oocytes recovered from the LUF follicle were in the stage of postmaturity, and the fertilization test in which they were used resulted in abnormal fertilization. These results indicate that LUF is an important cause of infertility and that periovarian abnormality might contribute to the failure of follicular rupture and postmaturity. PMID- 2212821 TI - [Tryptophan metabolism during the perinatal period]. AB - Tryptophan is considered to be an important indicator of nutritional changes during the perinatal period, from fetus to neonate. By means of high performance liquid chromatography (HPLC), we determined the concentrations of both free tryptophan (TRP) and its metabolite, kynurenine (KYN), in maternal venous plasma (M.V.) and umbilical arterial and venous plasma (U.A., U.V.) (n = 45) at the time of delivery. TRP and KYN concentrations were also measured in neonatal venous plasma (n = 11) for 3-5 days following delivery. RESULTS: 1) Day and night plasma TRP levels in non-pregnant women (n = 12), in pregnant women at term before labor (n = 12) and in delivering women (M.V.) (n = 45: day, n = 24: night, n = 21) were significantly different. 2) Both TRP and KYN concentrations were significantly higher in U.A. and U.V. than those in M.V., the concentration gradient being approximately 1:2, and a positive maternal-fetal relationship was observed (r = 0.586-0.944, p less than 0.01). 3) A positive relationship was observed between the venous-arterial gradient of umbilical cord tryptophan and the Kaup Index (r = 0.316, p less than 0.05). 4) In order to minimize individual variations, the ratios of TRP and KYN levels in newborn venous plasma to those in the umbilical arteries were calculated (n = 11). These ratios started to increase at 20-50 hours after delivery, which suggested that the first milk feeding may alter the metabolism of tryptophan in neonates. PMID- 2212822 TI - [Diagnosis of fetal heart rate without referring to uterine contraction]. AB - The purpose of this study is to evaluate intrapartum fetal condition only with reference to fetal heart rate (FHR) change. Sixty-five cases who had no severe complications were examined at 36 weeks to 42 weeks of gestation. Major cardiotocographic abnormalities were baseline bradycardia and severe variable deceleration. Late deceleration was not observed. The conventional program of automatic FHR diagnosis and a new computer program excluding uterine contraction (UC) algorithm were used. Digitalized FHR and UC data stored in a floppy disk were reproduced and analysed by either of the programs with and without UC. FHR scores and FD index obtained by the 2 programs were highly correlated with each other. Both the FHR score and FD index showed a correlation to PO2, PCO2, BE and pH of umbilical artery blood. There were no significant differences between the correlation coefficients for the 2 methods. The sensitivity of the FD index which predicted a pH of umbilical artery blood lower than 7.25 was 86.4% in both groups. And the specificity was 88.4% in the results obtained with UC and 90.7% without UC. There was no significant difference in sensitivity or specificity in both groups. PMID- 2212823 TI - [Study on the local estrogen biosynthesis in human uterine leiomyoma]. AB - The growth of uterine leiomyoma is regulated not only by the estrogen levels in blood, but also by estrogen production in the tumor itself. In this study, we investigated both the estrone formation (estrone sulfatase activity) and the transformation from estrone to estrone sulfate (estrone sulfotransferase activity) in human leiomyoma tissue. We compared them with those in the myometrium and endometrial tissues overlying and opposite a uterine leiomyoma node. We also measured the tissue concentrations of estrone, estradiol and estrone sulfate. Estrone sulfatase activity in the uterine leiomyoma was 0.49 +/- 0.08 nmol/h/mg protein (Mean +/- SE), and was lower than that in the myometrial tissue (0.76 +/- 0.09). Moreover, the enzyme activity was higher in the endometrium overlying the leiomyoma node (2.62 +/- 0.29) than in the endometrium opposite to it (2.10 +/- 0.24). On the other hand, estrone sulfotransferase activity in the myoma (20.2 +/- 2.4 pmol/h/mg protein) was higher than in myometrial tissue (16.7 +/- 2.3). The concentrations of estrone and estradiol in leiomyoma tissue were lower than in the tissues surrounding the leiomyoma. The tissue concentration of estrone sulfate was higher in leiomyoma tissues. These results suggest that estrone sulfate is hydrolyzed mainly by estrone sulfatase in the endometrium and myometrium surrounding leiomyoma nodes and the estrone formed may affect the growth of leiomyoma. PMID- 2212824 TI - [Immunohistochemical investigation of vimentin of uterine endometrial and endocervical adenocarcinoma]. AB - We investigated the localization and the immunoreactivity (IR) of vimentin in normal and cancerous glandular epithelia of the uterine corpus and cervix. The materials for the study were 33 cases of endometrial adenocarcinoma, 21 cases of endocervical adenocarcinoma, and 12 cases of uterine myoma which had normal endometrium and cervix. A similar study was also performed on smear materials. In normal endometrium, the vimentin was localized not only in the stromal cells but also in the epithelial cells. The IR of the vimentin in the epithelial cells was more prominent in the proliferative phase than in the secretory phase. On the other hand, in normal cervix, the vimentin was not localized in the epithelial cells. In endometrial adenocarcinoma, the IR of the vimentin was markedly or moderately positive in more than half of the cases. In endocervical adenocarcinoma, the IR of the vimentin was absent in all but 2 cases which were of the endometrioid type. The vimentin IR of the stromal cells was clearly observed in endocervical as well as endometrial adenocarcinoma. Very similar results were observed in the smear materials. In endometrial adenocarcinoma, the differentiation, the depth of myometrial invasion and the lymph node metastasis were regarded as the prognostic factors, and the vimentin IR appeared more intensive in the cases of well differentiated and superficial myometrial invasion. The above results showed that there was a remarkable difference between endometrial and endocervical epithelial cells in the vimentin IR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212825 TI - [Influence of chlamydial infection on fallopian tubes and its relation to cervical antigen and serum antibodies]. AB - Relation between chlamydial infection and oviductal changes and their screening method were studied by laparoscopic findings obtained from cases (group A; positive intracervical antigen detected by Chlamydiazyme) and from other cases (group B; negative antigen, but positive IgG antibodies detected by micro immunofluorescence, MIF). Group A consisted of 8 cases/15 tubes, and group B of 20 cases/40 tubes. These two groups were called infection groups, and there was a control group of 14 cases/28 tubes with negative results for both tests. (1) No significantly different incidence was noted between groups A and B for perifimbrial (PFA) and peritubal (PTA) adhesions and tubal occlusions (TO). (2) The control group had significantly lower incidences for the number of tubes with PFA or TO than the infection group. (3) Even in 20 cases without an alleged history of PID (pelvic inflammatory disease), 15 cases belonged to group B. It was concluded that chlamydial infection may cause latent tubal lesions and a chlamydial antibody study should be involved in predicting them, because it would detect an unignorable number of pathologic cases which would have probably been missed if cervical antigen test and/or alleged PID history were the only screening procedures used. PMID- 2212826 TI - p24 protein of a human T-lymphotropic virus type-I (HTLV-I) producing cell line (TCL-Kan) reacts with some normal pregnant women's sera. AB - Some HTLV-1 antibody carrying pregnant women, who are rated by the gelatin particle agglutination (PA) method, show no expression of HTLV-I antigen in their peripheral blood lymphocytes. Paying attention to this fact, the authors recently studied the reaction of the antibody contained in the PA-positive sera with the antigen protein used for the PA method. This study demonstrated that the protein responsible for non-specific reaction has a molecular weight of 24,000 and that the isoelectric point of this protein differs from that of HTLV-I specific protein. PMID- 2212828 TI - [In vitro long-term culture of trophoblast cells of early human placenta]. PMID- 2212827 TI - Progesterone protects oocytes from premature degeneration within the follicle. AB - The present study was designed to determine the effects of gestrinone (R2323) in the process of follicle rupture and oocyte maturation and degeneration in an in vitro perfused rabbit ovary model. In the first experiment, R2323 at 10(2), 10(3), or 10(4) ng/ml was added to the perfusate of one ovary. The contralateral control ovary was perfused simultaneously with medium alone. Thirty minutes after the onset of perfusion, 50IU of human chorionic gonadotropin (hCG) was added to the perfusate of both ovaries. All ovaries exposed to R2323 plus hCG or hCG alone ovulated. The addition of R2323 to the perfusate did not affect the ovulatory efficiency of ovaries treated with hCG. No significant difference in the percentage of ovulated ova or follicular oocytes demonstrating germinal vesicle breakdown was seen with R2323 treatment. R2323 increased the degeneration rate of ovulated ova in a dose-dependent fashion. In the second experiment, in which experimental ovaries were perfused with R2323 (10(4) ng/ml) plus progesterone (10(3) ng/ml) and the control ovaries with R2323 (10(4) ng/ml) alone ovulation occurred in response to hCG. However, the addition of progesterone to the perfusate reduced the degeneration-inducing effect of R2323 on both ovulated ova and follicular oocytes. In conclusion, R2323 appears to act as an antiprogesterone, thereby promoting the degeneration of oocytes. The increased production of progesterone in the preovulatory follicle following the gonadotropin surge protects oocytes from premature degeneration within the follicles. PMID- 2212829 TI - [Clinical study of preoperative radiotherapy of bladder cancer]. AB - From May 1982 to Nov. 1987, 33 patients with bladder carcinoma were treated with preoperative radiotherapy (20 Gy/5fr) and total cystectomy. The over all 3-year survival rate was 70%. For T1 and T2, 3-year survival rate was 100%, but only 55% and 0% for T3 and T4 respectively. In 23 out of 33 patients, preoperative T-stage was confirmed by TUR-BT. Down-Staging was recognized in 7 out of 23 patients (30%). They were 0 out of 1 patients for Tcis (0%), 2 of 3 for T1 (67%), 3 of 6 for T2 (50%), 2 of 11 for T3 (18%) and 0 of 2 for T4 (0%). This protocol of preoperative radiotherapy is thought to be favorable for T1 and T2 bladder carcinoma, but inadequate for T3 and T4 tumors. Consequently, it is considered that higher dose radiotherapy and postoperative chemotherapy are necessary for T3 and T4 bladder carcinoma. PMID- 2212830 TI - [Physical effects of treatment for childhood malignant solid tumors--a data to develop an assessment method of quality of life]. AB - To understand the effects of treatment of childhood malignant solid tumors on the children, thirty-two survivors were examined by a questionnaire method. The play performance scale for children (PPSC) was used to evaluate performance status in patients under 15 years of age. Ratings over 80 were obtained in 25 of 26 children (96.2%) and mean score was 94.2 +/- 8.4. Although the results of PPSC were satisfactory, several problems concerning patient's conditions including dental caries, short stature, radiation induced deformity and surgical scar, and physical disability in school life became clear. Other problems concerning parental conditions also became clear, that is, 25 parents (78.1%) had some anxiety about patient's future and only 13 parents (40.6%) told about the disease to their child. These problems should be evaluated objectively and discussed in the future. PMID- 2212831 TI - [Radiation therapy for human renal cell carcinoma transplantable to the nude mice]. AB - Efficacy of radiation therapy was studied using human renal cell carcinoma strain (AM-RC-3) implantable in nude mice. Cobalt 60 gamma-ray was used dosage of 5 Gy, 10 Gy, 15 Gy and 20 Gy in single, localized exposures of subcutaneously implanted tumors of the lower right femoral region. Therapeutic efficacy was determined using the Battelle Columbus Standard and evaluation of histological changes based on National Cancer Research Institute (Shimosato's classifications). Conclusion based on the obtained data are as follows: I) The T RW/C RW ratio on the tumor growth curve was 42% or less for all dosage groups except the 5 Gy group; dosages other than 5 Gy are believed effective. The 15 and 20 Gy dosage were particularly effective and the respective groups had RW of 0.96 and 0.95. II) Although Grade IIa and IIb changes were observed in the 15 and 20 Gy dosage groups, respectively, two weeks after irradiation, four weeks after irradiation all groups exhibited microscopic tissue formations that could be considered regrowth of tumor cells. Determination of histopathological effectiveness two weeks after irradiation is thought most suitable. III) Radiation therapy is appropriate as an adjuvant treatment in cases of renal cell carcinoma and should be used in combination with other therapies. PMID- 2212832 TI - [Radiation therapy for prostatic cancer]. AB - From February 1979 through May 1988, a total of 26 patients with adenocarcinoma of the prostate were treated with radiation therapy for the primary site. The actuarial 5-year survival rate was 59% for 14 patients with Stage C or less disease (A; 1 case, B; 2 cases, and C; 11 cases), and 10% for 12 patients with Stage D. The logrank test showed significant difference between these two groups (p less than 0.007). Rectal radiation injuries occurred in 2 cases (8%) at 7 months (grade I) and 6 months (grade II), respectively. From the analysis of local control and complication, optimum radiation dose ranged from 64.8 Gy to 68.4 Gy (TDF 100-106). In addition, optimum boost radiation field size with rotation technique (after whole pelvic irradiation of 40-45 Gy with anteroposterior opposing fields) ranged from 30 to 48 cm2. PMID- 2212833 TI - [The effect of a protein-bound polysaccharide (PSK) on lymphocyte subsets of peripheral venous blood and thoracic duct lymph]. AB - To study the effects of a protein bound polysaccharide (PSK) on the immune system in normal animal, lymphocytes subsets of both peripheral (PBL) and thoracic duct lymphocytes (TDL) were analyzed in 6 week old male SPF Wistar-Imamichi rats before and after free feeding of forage which contained 2% of PSK. PBL and TDL were obtained at the time before, 4 weeks after and 8 weeks after administration of PSK. Age matched rats without administration of PSK were used as a control. Following the peripheral blood cell counts were carried out, lymphocytes subsets such as ratio of total T cells helper/inducer T (Th) cell, suppressor/cytotoxic T (Ts) cell and B cell were assayed using W3/13, W3/25, 0 X 8 and 0 X 4 monoclonal antibodies with laser flow cytometric technique (Orthospectrum III Orthodiagnostics). In terms of the PBL, number of total T cells and Th cells in PSK treated group were significantly lower than that of controls. However no statistical different could be obtained between these two groups in relation to the number of Ts cells and B cells. On the other hand, the number of T cells and Th cells in TDL of PSK treated groups were significantly higher than that of controls while Ts cell and B cell number did not show no apparent differences between these two groups. These findings indicate that oral administration of PSK have a potency to accelerate the transport of T cells from blood stream to lymphatic channel and also regulate their distribution in a normal healthy animals. PMID- 2212834 TI - [Studies on intracellular kinetics of ara-C triphosphate in HL-60, human leukemia cells in relation to reasonable administration of ara-C]. AB - To study the pharmacokinetics of 1-beta-D-arabinofuranosylcytosine (ara-C), which is one of the main drugs used in chemotherapy for acute leukemia, its intracellular metabolism was investigated using HL-60 cells derived from human acute non-lymphocytic leukemia. The concentration of the drug and its metabolites in the cells were serially determined and the following results were obtained. 1) The uptake of ara-C into HL-60 cell (1 X 10(7)/ml) was very rapid when they were incubated with 2 microM ara-C. The total intracellular ara-C content per 10(9) cells exceeded the ara-C concentration in the extracellular fluid at about 7 minutes after the start of incubation. It reached about 4 times higher than the extracellular concentration after 60 minutes. 2) Conversion of ara-C to the active form, ara-CTP, was also rapid. The intracellular concentration of ara-CTP was about 3 times higher than the ara-C concentration in the extracellular fluid after incubation for 60 minutes. 3) Total accumulation of ara-C in the cells was dependent on the extracellular ara-C concentration up to a concentration of 100 microM. The production of ara-CTP occurred in such a way that, when the extracellular ara-C concentration was lower than 10 microM, more than 90% of the uptake of ara-C was converted to ara-CTP, while at concentrations above 10 microM the efficiency at production (the ratio of total ara-C to ara-CTP production) was decreased. The maximum intracellular ara-CTP concentration was estimated to reach to 45 microM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212836 TI - [Study on the clinical usefulness of NCC-ST-439 in cases of digestive tract cancer]. AB - NCC-ST-439 is a monoclonal antibody established from human stomach cancer xenografted nude mice. The values of NCC-ST-439 were measured in 139 cases with various digestive tract cancers and 294 cases with benign digestive tract diseases with the NCC-ST-439 EIA kit (Nihon Kayaku Co., Ltd.), and its clinical usefulness was compared with those of CA19-9 and CEA. The positive rates of NCC ST-439 in cases of digestive tract cancer were high, i.e., 66.7% for cancer of the bile duct, 58.3% for pancreatic cancer and 52.9% for colorectal cancer. In the benign digestive tract diseases, the overall positive rate seen in case of cholelithiasis and cholangitis, chronic gastritis, benign colorectal diseases and hepatitis, was only 3.7%. The positive rate of NCC-ST-439 was lower than those for CA19-9 and CEA in cases of stomach cancer, colorectal cancer and liver cancer, but it was the same as that of CA19-9 and higher than that of CEA in cases of biliary tract cancer and pancreatic cancer. The false positive rate of NCC-ST-439 in benign diseases of the digestive tract was the lowest among the three markers. With respect to sensitivity, specificity and efficiency, CA19-9 showed the highest sensitivity, but NCC-ST-439 and CEA showed better specificity than CA19-9, and NCC-ST-439 showed the highest efficiency. In combination assays using combinations of NCC-ST-439, CA19-9 and CEA, the positive rates for ST-439 alone were 22.1% for stomach cancer, 52.9% for colorectal cancer, 15.0% for liver cancer and 58.3% for pancreatic cancer, while the combined rates increased to 51.9%, 70.6%, 75.0% and 66.7%, respectively. In an investigation of changes with time in NCC-ST-439 values during chemotherapy of various types of digestive tract cancer, there was a decrease in PR cases, no change in NC cases and a tendency to increase in PD cases. These results suggested that it was possible to apply NCC ST-439 clinically. PMID- 2212835 TI - [Radiotherapy and chemotherapy in stages I and II non-Hodgkin's lymphomas of Waldeyer's ring]. AB - Sixty-four patients with stages I and II non-Hodgkin's lymphomas (NHL) involving Waldeyer's ring treated between 1970 and 1987 were reviewed. Patients with stage II NHL were subdivided into stage II 1 (limited type) and stage II2 (advanced type) from the state of neck nodes. Stage II1 was defined as involvement of unilateral cervical nodes less than 4 cm in diameter as well as Waldeyer's ring involvement. Other stage II cases were classified as stage II2. All 17 patients with stage I NHL were treated with radiation therapy alone. Their diseases were well controlled, and none of them died of causes related to the lymphoma. Among 14 patients with stage II1 NHL, the 5-year survival rate for the 9 patients treated with radiation therapy alone was 87.5%. Until 1982, 19 of 21 patients with stage II2 NHL treated with radiation therapy alone or radiation therapy and adjuvant chemotherapy (VEMP or COPP) died within 5 years mainly of disseminated diseases. Since 1983, CHOP has been used as the main treatment as well as radiotherapy for the 12 stage II2 NHL patients. So far, only 3 of them relapsed and 2 of them died of causes related to the lymphoma. Only 1 of these 12 patients was T-cell lymphoma compared to 7 of 9 stage II2 patients before 1982. This suggests that patients with stage I and those with limited stage II can be safely treated with radiotherapy. Also aggressive chemotherapy as well as radiotherapy should be used for patients with advanced stage II NHL involving Waldeyer's ring. PMID- 2212837 TI - [Local injection of high-dose CDDP to the advanced gynecological cancer]. AB - We investigated the efficacy of local injection of high-dose CDDP. The subjects were 16 patients with advanced gynecological cancer or tumor recurrence, in whom systemic administration of CDDP was inadvisable because of advanced age or associated complications (12 cases of cervical carcinoma, 2 cases of endometrial carcinoma, 1 case of ovarian carcinoma, and 1 case of vulvar carcinoma). In 14 cases, CDDP was injected locally to the tumor mass, using a single dose of 50-300 mg. In 2 cases, a single dose of 10-20 mg of CDDP was infused into the uterine cavity. The effects of the therapy were evaluated by cytodiagnosis, tumor markers, CT, and performance status. In all cases, an antitumor effect was noted, and seven subjects survived for at least 24 months following these therapy with CDDP. One patient developed vesicovaginal and rectovaginal fistulae after local injection of CDDP following high-dose radiotherapy. We investigated the plasma concentrations of free and total platinum after CDDP application with doses from 60-200 mg/body. Plasma concentrations showed a biphasic pattern (phase alpha and phase beta), and the peak plasma concentration of CDDP was lower than that following intravenous administration of the same dose. From these results, it was suggested that a large dose of CDDP can be injected into the tumor tissue itself and the surrounding tissue with comparatively few side effects. It will be possible to administer large dose of CDDP in this way to the terminal patients to whom there is currently no other appropriate method of treatment. The performance status of our subjects was improved, and we expect that wider use of this method will improve the quality of life for end-stage patients. PMID- 2212838 TI - [Index of tumor response by in-vivo 31P-MRS--T1 effect as a new predicting index of therapeutic effects]. AB - We observed the metabolism of the Yoshida sarcoma by in-vivo 31P-MRS, using two varieties of repetition time (TR), i.e., TR2s and TR10s. It was measured before the injection of 5FU and 4, 24, 48 hours after the injection. In the each time, PME/ATP ratio, intracellular pH, and TR10/TR2 ratio of PME which reflects the T1 value of PME, were calculated. TR10/TR2 ratio of PME decreased 4 and 24 hours after the injection of 5FU and recovered 48 hours after the injection to the same level before the injection. However decrease of PME/ATP ratio was not observed until 48 hours after the injection of 5FU, when apparent tumor regression appeared. These results suggested that the T1 value of PME decreased prior to the PME changes and when the PME decreased, the intracellular environment of PME recovered to the same state before the therapy. It was considered that the TR10/TR2 ratio of PME offers significant information different from the PME/ATP ratio. It is possible to use the TR10/TR2 ratio as a predicting index for the therapeutic effects. PMID- 2212839 TI - [Esophageal cancer metastatic to the kidney: report of a case]. AB - On December 12, 1988, 51-years-old man was admitted to our clinic with asymptomatic gross hematuria. He had been undergone total esophagectomy for esophageal cancer in the surgery service of our hospital on June 22, 1987, and histopathological diagnosis was squamous cell carcinoma, Stage III, a2, n(-), m0, pl0, ly(+), V(+). X-ray CT revealed a irregular, obscure bordered tumor image in the left kidney and angiography showed a hypovascular tumor. On December 20, nephrectomy was performed. Histologically, it proved to be squamous cell carcinoma metastasized from esophageal cancer. The present case is the 11th of those cases which have been clinically diagnosed as renal metastasis of esophageal cancer in Japan. An extremely small number of clinically reported cases compared with autopsy cases are thought to be ascribable to scarce detectability while living of such metastasis, but not to its rare occurrence. The coming diagnostic improvement may well make such case more and more increasing. PMID- 2212840 TI - Rectal endosonography for the visualisation of the anastomosis after anterior resection and its relevance to local recurrence. AB - Rectal endosonography can be used to detect and localise recurrent rectal carcinoma. Distal and proximal to a rectal anastomosis the separate layers of the bowel wall as seen by rectal endosonography are well defined but at the precise level of the anastomosis separation of the layers is lost and they appear to merge. By studying histological sections of a normal anastomosis we have demonstrated that this loss of definition seen endosonographically correlates with the histological appearances. These appearances of the normal anastomosis provide a baseline image for the identification of recurrences in the region of the anastomosis. PMID- 2212841 TI - Growth hormone increases the bursting strength of colonic anastomoses. An experimental study in the rat. AB - The effect of growth hormone on the bursting strength of left colonic anastomoses was investigated experimentally. Seventy-two 3 month-old female rats were randomized into two groups receiving daily injection of either saline (controls) or 2.0 mg biosynthetic human growth hormone per kg body weight per day. All injections were started 7 days before a left colonic resection and anastomosis, and continued until sacrifice at the 2nd, 4th or 6th post-operative day. The bursting strength of the anastomoses was tested in anaesthetized, living rats. The bursting pressure and the bursting wall tension of the growth hormone treated animals were increased two-fold on the second post-operative day (2p less than 0.005) and three-fold on the fourth post-operative day (2p less than 0.05), compared with controls. There was no difference in the bursting pressure or the bursting wall tension on the sixth postoperative day. The mass of the resected segment was increased by the pre-operative growth hormone treatment, whereas the hydroxyproline content was unchanged. In conclusion, treatment with biosynthetic human growth hormone increases the strength of colonic anastomoses in the early phases of healing. PMID- 2212842 TI - A technique for the dynamic assessment of anal sphincter function. AB - A technique which renders continuous measurement of the cross-sectional area and pressure of the anal canal possible during distension and contraction of the anal sphincter has been developed. Electromyography of the external sphincter is measured simultaneously. With this technique a more detailed assessment of anal sphincter function is possible, including the opening and closing pressures of the sphincter at rest, anal compliance, anal hysteresis and the maximal closing pressure during squeeze. The results of in vitro measurements, measurements on 16 healthy subjects and 6 patients with faecal incontinence are presented. PMID- 2212843 TI - Adenocarcinoma of the rectum treated by abdominoperineal excision: multivariate analysis of prognostic factors. AB - The aims of this study were to describe the results of 100 consecutive abdominoperineal excisions, and to try to define homogeneous subgroups of survivors using the Cox regression analysis model. There was one postoperative death. No patient was lost to follow-up. Overall 5-year survival rate was 45%. Multivariate analysis selected 3 prognostic factors: lymph node involvement (p less than 0.001), local tumour extent (P = 0.08), and extension to adjacent organs (p = 0.03). Four subgroups of patients were defined. Best survival was observed in patients (n = 43) with tumour invading into the subserosa (W1) or less and without lymph node metastasis (N0), with a 5-year survival of 82% (group 1). Patients in Group 2 (n = 18) had a tumour invading into the muscularis propria or less with lymph node metastasis (W0 N+), or into the serosa or perirectal fat without lymph node invasion (W2 N0), with a 5-year survival of 51%. Patients in Group 3 (n = 17) had a tumour invading into the subserosa with lymph node invasion (W1 N+) or extension to adjacent organ without lymph node invasion (W3 N0) with a 5-year survival of 24%. Patients in group 4 (n = 22) had extension into the serosa or perirectal fat or more with lymph node invasion (W2 N+) with a 5-year survival of 2%. This scoring system is simple, practical and easy to apply. If it can be confirmed by other studies, its routine adoption could be justified. PMID- 2212844 TI - The first year with a J-pouch. A prospective evaluation. AB - Proctocolectomy and construction of a pelvic pouch with ileo-anal anastomosis is now an established method in the treatment of ulcerative colitis, but various procedures are still under evaluation. This series comprises 97 patients with a 20 cm long J-shaped pouch and a short rectal cuff of 2-5 cm, prospectively evaluated after 1, 3, 6 and 12 months. Eight patients had their pouch removed because of septic complications. All the remaining patients evacuate spontaneously, although around one third still use constipating agents after 1 year. The stooling frequency gradually diminished from 7 (4-15) per 24 h to 4 (2 6) after 12 months. Continence also gradually improved during this period. No patient was incontinent of faeces but 13% still experienced episodes of minor soiling after 12 months. The procedure has proved to be safe providing patients are carefully selected, and 90% achieve a satisfactory or acceptable functional result. PMID- 2212846 TI - Sigmoid stricture at colonoscopy--an indication for surgery. AB - Strictures of the sigmoid colon continue to pose a diagnostic dilemma. They commonly appear to be due to diverticular disease but carcinoma must always be excluded. In some cases diverticula may be present but in others there is no obvious cause for the stricture. In a series of 1039 consecutive colonoscopies performed between 1984 and 1986, 19 cases of sigmoid stricture that could not be negotiated with the colonoscope were encountered. In each case the cause of the stricture could not be demonstrated. Fifteen patients (79%) underwent laparotomy primarily on clinical grounds or with barium enema findings suggestive of carcinoma. A final diagnosis of diverticular disease was made in nine cases and adenocarcinoma is six cases. Barium enema was a poor predictor of malignancy in a stricture. Four patients were treated conservatively and two of these patients continued to have significant symptoms due to diverticular disease. This experience suggests that sigmoid strictures that prevent the passage of a colonoscope should be resected when the cause of the stricture is not apparent. PMID- 2212845 TI - Proctocolectomy and stapled ileo-anal anastomosis without mucosal proctectomy. AB - The present study compared the outcome of a small series of patients (7 cases) who underwent total proctocolectomy without mucosal proctectomy and stapled ileal pouch-anal anastomosis made at the apex of the anal transitional zone, with our previous experience (17 cases) in which the ileal pouch was anastomosed at the dentate line after mucosectomy. Though not statistically significant, our limited experience showed excellent clinical results with better continence and discriminating ability of flatus from faeces in the former group. The resting anal pressure profile was not changed postoperatively. The operation time was significantly reduced compared with our previous approach which was a time consuming procedure. There was an indication that risk of complications (pelvic sepsis and haemorrhage) was less. PMID- 2212847 TI - Peroperative contamination and anastomotic leakage after resection for left colon stenosis. An experimental study in the rat. AB - In this experimental study the effect of peroperative faecal soiling on immediate postoperative anastomotic leakage after resection and primary anastomosis of a left colon obstruction was evaluated. Faecal soiling was quantified by a standardized irrigation of the abdominal cavity and then culturing of the fluid. An increased peroperative soiling was found after resection of a stenosis compared to resection of a non-stenotic bowel. Anastomotic complications were correlated to the degree of bacterial contamination and a breakpoint of 10(4) CFU/ml was found. Immediate postoperative leakage, tested with the bacteria Serratia marcescens, was not increased in the stenosis group. Thus, peroperative bacterial contamination seems to be one important factor in developing anastomotic complications after resection of colonic obstruction while an immediate leakage of bacteria through the anastomosis seems to be less important. PMID- 2212848 TI - The effect of diverting colostomy on anastomotic healing after resection of left colon obstruction. An experimental study in the rat. AB - A standardized stenosis of the left colon was created in the rat model. After four days the stenosis was resected and a primary anastomosis made. Half of the animals (n = 21) were randomized to a proximal diverting colostomy and the other half to a non-colostomy control group. On postoperative days two and seven anastomotic complications were recorded and anastomotic strength was determined. Collagen content in the anastomotic area was measured. In the colostomy group no anastomotic complications occurred, while 6/21 (29%) animals in the non-colostomy group had complications. On day two there was no difference between the groups as regards anastomotic strength and collagen content. After a week, however, the control group showed a significant increase in both anastomotic strength and collagen content which was not observed in the colostomy group. The absence of increase in anastomotic strength in the colostomy group had no adverse effect on anastomotic healing, as judged by complications. Thus, a diverting colostomy may be of value in reducing anastomotic complications after resection of a left colon obstruction. PMID- 2212850 TI - Packing the perineal wound with a resorbable (polyglactin) net in difficult cases following abdomino-perineal excision of the rectum. PMID- 2212851 TI - A history of the Central Society for Clinical Research. PMID- 2212849 TI - Anal manometry. PMID- 2212852 TI - Photosensitization of viral particles. PMID- 2212853 TI - Regulation of the pathophysiology of tumor necrosis factor. PMID- 2212854 TI - Isolation and quantitation of human erythrocyte deformability classes. AB - A new technique is described that fractionates erythrocytes according to their deformability. The method is a modification of the method of Beutler et al. (J Lab Clin Med 1976;88:328-33), in which small cellulose columns are used to remove white cells from blood samples. We find that when the length-to-width ratio of the columns is increased, the mixed cellulose bed also fractionates the red cells. Measurement of mean cell volume, mean corpuscular hemoglobin concentration, hemoglobin level, deformability index, and cell density showed that deformability is the physical property of the erythrocyte that forms the basis for the fractionation. This is a separation modality that complements the numerous density gradient techniques for red cells. The following experimental results can be obtained by using the technique: (1) The number of cells with a defined degree of rigidity can be quantitated in an erythrocyte population. (2) Large numbers of cells that differ with respect to their deformability can be isolated. (3) Application of the method to sickle cells has quantitated the remarkable heterogeneity of these cells with regard to their deformability. PMID- 2212855 TI - Acute effects of captopril and ibuprofen on proteinuria in patients with nephrosis. AB - Captopril decreases protein excretion in patients with nephrosis. To evaluate whether captopril has an acute antiproteinuric effect and to evaluate the role of changes in renal hemodynamics or glomerular permselectivity on this effect, renal clearance studies were performed in patients without diabetes but with nephrosis. Protein excretion and renal hemodynamics were measured at baseline and after the administration of captopril. To measure the contribution of renal prostaglandins, patients were restudied on a separate day, after the combined administration of captopril and the prostaglandin synthetase inhibitor ibuprofen. Both treatments significantly reduced mean protein excretion, but the change was greater with combined therapy than with captopril alone (40.6% vs 20.0%). Mean glomerular filtration rate (GFR) decreased by 4.8% (not significant) and 16.5% (p less than 0.001), and filtration fraction (FF) decreased by 13.6% (p less than 0.001) and 14.9% (p less than 0.001) after captopril alone and combined therapy, respectively. No significant correlation was found between changes in proteinuria and changes in GFR or FF after treatment with captopril alone. In contrast, the decrease in proteinuria correlated with the change in GFR after combined drug administration (r = 0.68, p = 0.06). The ratio of immunoglobulin G to albumin clearance, an index of glomerular permselectivity, was unaffected by captopril but decreased significantly (by 43%) after combined drug administration. The results suggest that the acute antiproteinuric effect of captopril is not due to changes in FF, GFR, or glomerular perselectivity. The addition of ibuprofen enhances the antiproteinuric effect of captopril by decreasing the GFR as well as by enhancing the permselectivity of the glomerular capillary membrane. PMID- 2212856 TI - Suppression of urinary albumin excretion in diabetic rats by 4'(imidazol-1-yl) acetophenone, a selective inhibitor of thromboxane synthesis. AB - Thromboxane contributes to the regulation of glomerular hemodynamics in experimental models of diabetes and has been implicated as mediator in some models of glomerular injury. In the present study we examined urinary albumin, protein, and thromboxane B2 (TXB2) excretion during the 170 days after induction of diabetes by injection of streptozotocin in insulin-treated moderately hyperglycemic (200 to 400 mg/dl glucose) rats (SDRs). The effects of a thromboxane synthesis inhibitor, 4'-(imidazol-1-yl)acetophenone (TXI) (100 mg/kg/day) on these parameters were also assessed. Urinary TXB2 and albumin excretion in SDRs was not different from that in normal rats between 7 and 90 days but were three times higher than normal in SDRs at 125 and 170 days after induction of diabetes. In SDRs, urinary protein excretion was higher than in controls at 170 days but not at earlier time points. Inulin clearance (CIn) of SDRs was significantly higher than control values at 7 and 90 days and was not influenced by TXI during this period. At 170 days CIn was not significantly different in SDRs and normal rats. By contrast, albumin clearance (CAIb) and fractional CAIb were elevated in SDRs when compared with those values in normal rats. Treatment of SDRs with TXI for 170 days completely prevented the rise in urinary TXB2, albumin, and protein excretion, as well as the rise in fractional CAIb, but did not alter prostaglandin E2 (PGE2) excretion. TXI also increased CIn in SDRs to levels that were significantly higher than normal at 170 days. TXI had no significant effect on urinary PGE2, TXB2, albumin, or protein excretion or on CIn in normal rats and did not influence blood pressure or blood glucose in normal rats or SDRs. The results suggest a role for thromboxane in the mediation of albuminuria in the SDR. PMID- 2212857 TI - Assessment of platelet antibody by flow cytometric and ELISA techniques: a comparison study. AB - Two different methods for evaluating platelet antibody were used to study 12 normal subjects and 24 patients consisting primarily of intravenous drug users (IVDUs) who were positive for human immunodeficiency virus (HIV). Total platelet associated immunoglobulin G (IgG) and immunoglobulin M (IgM) were measured by enzyme-lined immunosorbent assay on platelet lysate, and platelet surface associated IgG and IgM were measured by semiquantitative flow cytometry. IgG and IgM values showed significant correlations between the two measurement methods. Mean platelet surface IgG and total IgG were 3.6 and 4.3 times greater, respectively, in IVDUs than in controls, and platelet IgM was also significantly higher in IVDUs than in controls as measured by both techniques. Although mean platelet immunoglobulin levels were higher in the IVDUs with thrombocytopenia than in IVDUs with normal platelet counts, these differences did not achieve significance. These data show that platelet IgG and IgM levels are increased in IVDU-associated HIV infection and suggest that these increases are not confined to patients manifesting thrombocytopenia. The herein described platelet surface antibody and total platelet antibody measurements appear to be equally useful in studying this patient population. Specific details for generating platelet associated immunofluorescence units are discussed. PMID- 2212858 TI - DNA sequence analysis of three inhibitor-positive hemophilia B patients without gross gene deletion: identification of four novel mutations in factor IX gene. AB - Three hemophilia B patients with anti-factor IX antibodies who had no detectable gross deletion of the factor IX gene by Southern blotting analysis were investigated at the molecular level. All eight exons, accompanied by their splicing junction sites and presumptive promoter regions of the factor IX gene in these patients (total 5.5 kb in length) were amplified with the use of the polymerase chain reaction, followed by complete nucleotide sequence analysis. Three different types of novel single base substitutions and a 2 base-pair nucleotide deletion were identified. Patient HB-5 had two point mutations in his factor IX gene. One was located at the promoter region at nucleotide -793 and the other (C-to-T transition) was found in exon VI of the gene changing Gln-191 to a stop codon. Patient HB-6 had a point mutation (G-to-A) in the splice acceptor site, which interrupted the normal splicing of the last intron G. A small two nucleotide deletion in exon III was detected in patient HB-7 and yielded frameshifted amino acids and terminated by a stop codon. These resuslts suggest that not only the gross gene deletion of factor IX gene but also the point mutations or small nucleotide deletion that may cause the interruption of coding informations for mature protein synthesis is predisposed to development of anti factor IX inhibitors in patients with hemophilia B. PMID- 2212859 TI - Immune activation is associated with phenylhydrazine-induced anemia in the rat. AB - Long-term phenylhydrazine (PHZ) treatment caused pronounced anemia and a concomitant increase in the numbers of circulating leukocytes in Long-Evans rats. The leukocytosis was caused mainly by an elevation in mononuclear cells, most notably in the lymphocyte population. PHZ has been reported to cause the direct lysis of erythrocytes by nonimmune mechanisms. However, recent reports indicate that PHZ can cross-link red cell band 3 protein (senescent antigen), resulting in the binding of autologous immunoglobulin G (IgG). Recognition of this complex by macrophage Fc receptor mechanisms triggers rapid erythrophagocytosis-in the spleen and possibly the liver as well. In our study, analysis of the blood, bone marrow, and spleen cells of long-term (1 to 6 weeks) PHZ-treated rats was performed by using flow cytometry. Total serum IgG levels were determined by radial immunodiffusion, and antibodies reactive with red cells that were sensitized to PHZ either in vivo or in vitro were titered by using the indirect Coombs' method. Serum prostaglandin E2 titers also were determined at different time intervals after PHZ administration. The results indicate that PHZ induces an increase in circulating antibody and prostaglandin E2 titers that correlates with the onset of anemia and that the serum of PHZ-treated rats can induce anemia in normal recipients after passive transfer. Cytofluorographic studies revealed a marked increase in the B-cell population of the peripheral blood and spleen and an altered ratio T-helper to T-suppressor cells at certain time intervals after PHZ injection. The results indicate that in addition to inducing senescence-like alterations in erythrocyte membrane proteins, PHZ stimulates the production of the autologous IgG that recognizes these sites and promotes lymphoid blastogenesis, most notably in the B-cell lineage. PMID- 2212860 TI - Posttransplant anti-glomerular basement membrane nephritis in related males with Alport syndrome. AB - This report describes the development of anti-glomerular basement membrane (GBM) glomerulonephritis after kidney transplantation in related males with Alport syndrome. Antibodies in sera from one of these patients stained normal GBM, Bowman's capsule, tubular basement membranes, and epidermal basement membranes but did not stain tissues from an unrelated Alport male. The target antigen was found to be a 26 kd peptide of the noncollagenous domain of basement membrane collagen. This study provides further evidence of the importance of abnormalities of basement membrane collagen in the pathogenesis of the Alport nephropathy. We speculate that certain mutations at the Alport locus, such as large intragenic deletions or frame-shift mutations, may be associated with failure to develop immune tolerance to epitopes on this 26kd peptide. In the setting of permissive immune response and regulation, transplantation of a normal kidney may result in the generation of anti-GBM antibodies. PMID- 2212861 TI - Connective tissue activation. XXXIV: Effects of proteolytic processing on the biologic activities of CTAP-III. AB - Microheterogeneity of connective tissue activation peptide III (CTAP-III) was revealed by preparative and analytical isoelectric focusing. Proteolytic activities in human platelet preparations resulted in four cleavage products of platelet-derived CTAP-III. Three isoforms (CTAP-III des 1-13, des 1-14, and des 1 15/NAP-2) stimulate [14C]glycosaminoglycan synthesis; two isoforms also promote [3H]DNA synthesis in human fibroblast cultures. Elastase (from porcine pancreas) cleavage of human platelet-derived CTAP-III and rCTAP-III-Leu-21 to the des 1-15 isoforms was associated with either preservation of specific anabolic biologic activity or an actual increase in specific activity. Nonenzymatic glycosylation of lysyl residues and deamination of the NH2-terminal asparagine of platelet derived CTAP-III were commonly present, but did not correlate with the biologic activities that were measured. Protein sequence homology shows CTAP-III and its isoforms to be members of a family of proteins (including NAP-1/II-8, MGSA, and platelet factor-4) known to be associated with growth, wound repair, inflammation, and neoplasia. The consequences of proteolytic processing reported here for CTAP-III may be characteristic of the other proteins in this group. PMID- 2212864 TI - The effect of alpha-hemoglobin gene deletions on the red blood cells' mean cell volume and hemoglobin levels. PMID- 2212863 TI - Origins and early days of the Central Society for Clinical Research. 1977. PMID- 2212862 TI - Use of ektacytometry to determine red cell susceptibility to oxidative stress. AB - To define a more sensitive and reliable method to determine changes in the overall cellular characteristics of erythrocytes after oxidative damage, we used a viscodiffractometric method (ektacytometry) to measure the effect of oxidative stress. Erythrocytes were incubated in the presence of hydrogen peroxide, t-butyl hydroperoxide, or cumene hydroperoxide in phosphate buffer. This treatment resulted in decreased cellular deformability of the intact erythrocytes. In addition, deformability and fragility measurements of the erythrocyte ghost membranes indicated an increased membrane dynamic rigidity and altered-mechanical stability as a consequence of oxidant stress. These changes were observed before the onset of hemolysis. The observed decrease in deformability was accompanied by oxidation of hemoglobin, alterations of membrane proteins, and lipid peroxidation. To continuously measure the time course of the decrease in deformability in intact erythrocytes under oxidative stress, a new ektacytometric method was developed. Erythrocytes were oxidatively challenged within the viscometer at a constant osmolality and shear stress. The change in deformability was monitored and a typical range was defined for erythrocytes from normal individuals. Comparison of erythrocytes from patients with sickle cell disease with those from normal individuals demonstrated a higher susceptibility of sickle red cells toward oxidative stress. PMID- 2212865 TI - A "treated" model for severe hemorrhagic shock: a comparison of conventional and germ-free animals. AB - In an unanesthetized "treated" model of severe hemorrhagic shock, a bacteremia originating from the animal's enteric flora was demonstrated by finding radiolabeled Escherichia coli in the blood as early as 2 hr after the onset of shock. In 50 patients admitted to our trauma unit, the observation was similar, with 56% positive blood cultures, when their mean arterial blood pressure was 80 mmHg or less. The relationship of bacterial translocation and the high post-shock mortality in our conventional (CV) animal model is being evaluated in germfree (GF) Sprague-Dawley rats. Preliminary observations in 15 GF animals showed 80% survival at 24 hr post-shock, 54% at 48 hr, and 42% at 72 hr compared with those of CV animals in previous experiments with survival at similar times of 73%, 20% and 7%, respectively. PMID- 2212866 TI - Platelet aggregation in septic shock. Effect of pentoxifylline. AB - In contrast to normal individuals, patients suffering from adult respiratory distress syndrome (ARDS) due to septic shock had increased platelet aggregation and circulatory platelet aggregates in blood. In vitro incubation with pentoxifylline (Trental) decreases platelet aggregates. This suggests that in addition to its platelet aggregation inhibitory effect, it also causes platelet disaggregation. Platelet aggregate patterns were shown to normalize two weeks after clinical recovery. PMID- 2212867 TI - In vitro cardiac function in early sepsis. AB - The involvement of the myocardium in the injury resulting from bacteremia has been somewhat controversial. Recently, some investigators have suggested that the transition from an early stage of sepsis, in which the cardiovascular system is stable and mortality is relatively low, to the late or preterminal stage of sepsis is a result of cardiac dysfunction. Here, however, data are presented to show that contractile defects and loss of myocardial reserve occur even early during a septic episode, i.e., at a time when cardiac output is elevated or normal. Efforts to determine the mechanism of the cardiac dysfunction are described. These entail studies of whole heart performance under conditions of varying the calcium availability for contraction and assessment of subcellular organelle function. The data indicate that calcium dyshomeostasis may at least partially contribute to the cardiac dysfunction of sepsis. The in vivo adequacy of cardiac function probably results from the capacity of the myocardium in early sepsis to respond to catecholamine support of chronotropy and inotropy. PMID- 2212868 TI - Response of germfree animals to shock. AB - Many current models of septic shock in conventional (CV) rats utilize cecal ligation and perforation. That germfree (GF) status offered no increased protection in shock, compared with the effect on CV controls, was shown in early studies. Appropriate fluid therapy, however, did increase survival. Our laboratory's efforts to determine the influence of the GF rat's enlarged cecum on its early response to hemorrhagic shock can be summarized as follows. Ten litters of 8 GF rats each were randomly divided into four groups with two animals/group: CV control, GF control, CV cecectomized and GF cecectomized. Littermates were cecectomized at seven weeks and bled at 14 weeks. Under methoxyflurane anesthesia, the rats were cannulated (femoral artery), heparinized, restrained, and allowed to awaken. Blood pressure was maintained at 60 mmHg for 1 hr and at 50 mmHg for 3 hr by adjusting the height of a burette reservoir. In the GF cecectomized rats, 95% (19/20) survived, whereas only 50% (10/20) of the other three categories survived. Cecectomized GF rats required only 3% of their shed blood, whereas, the other three groups needed 10 to 15%. Cecum from the GF rat contains a 5-fold greater quantity of bioactive and vasoactive substances than the cecum of its CV control, and may cause these changes in basic cardiovascular parameters in GF control rats: decreased cardiac output, blood volume, heart weight, and vasoconstriction to epinephrine in mesenteric arterioles, plus increased hemoconcentration and blood viscosity. In cecectomised GF rats, these parameters return to the CV levels and help to protect the animal during the early hypovolemic trauma. Clearly, the rat's cecum produces significant cardiovascular effects that need to be considered when evaluating experimental models for trauma or stress. PMID- 2212869 TI - Diaphragmatic fatigue after endotoxemic shock in rats: in vitro function and metabolism. AB - A rat model was used to study the effects of endotoxemic shock in vivo on diaphragmatic tension generation and diaphragmatic metabolism in vitro. Animals were injected with E. coli lipopolysaccharide (30 mg/kg) and killed at fixed times after injection. The hemidiaphragms were isolated in an organ bath, and tension generation was measured during electrical stimulation of the phrenic nerve or diaphragmatic muscle. Diaphragmatic oxygen consumption was measured in vitro during rest and during in vivo stimulation. Adenosine triphosphate and glycogen concentrations were measured in vivo before the animals were killed and in vitro. Tension generation was reduced in a time-dependent fashion after endotoxin at all stimulation frequencies. Both contractile fatigue and transmission fatigue were present. Glycogen stores were reduced but not depleted. ATP concentration was reduced in vivo but recovered in vitro. Diaphragmatic oxygen consumption was reduced in vitro at rest and during stimulation. The results suggest that endotoxemic shock results in diaphragmatic fatigue in a time dependent fashion, that impaired neural or neuromuscular transmission is present in vitro, and that impaired oxygen consumption in the shocked diaphragm is associated with reduced high-energy-phosphate stores. PMID- 2212870 TI - [Hemodynamic impact of pressotherapy]. AB - We study the hemodynamic effects of pressotherapy in 11 patients (mean age : 68 +/- 10 years) with uncomplicated acute myocardial infarction (n = 6) or with chronic ischemic heart failure (n = 5). We measure the right auricular pressure (RAP), the mean pulmonary arterial pressure (MPAP) and the pulmonary wedge pressure (PWP), before, during pressotherapy (MPAP) and the pulmonary wedge pressure (PWP), before, during pressotherapy (T 20 min) and 30 minutes after the end of pressotherapy (T 30 min). We use five-chambered leg garments with 80 mm Hg pressure during 20 minutes. The wavelike action (from the bottom to the top) is intermittent: the compression time is 10 second (sec); compression is maintained during 60 sec; deflation time is 15 sec. After 20 minutes pressotherapy (t 20) the 3 variables increase: RAP: from 3.6 +/- 5 to 7 +/- 7 mm Hg (P less than 0.001), MPAP: from 25 +/- 14 to 29 +/- 17 mm Hg (p less than 0.01) and the PWP from 10 +/- 8 to 17 +/- 11 Hg (p less than 0.01). This rise is particularly important in heart failure patients: from 18 +/- 8 to 29 +/- 8 mm Hg for the PWP, with cough in one patient. At T 30 these 3 variables decrease and return nearly to initial values: respectively 2.7 +/- 4.7 (RAP), 24 +/- 14 (MPAP), 12 +/- 8 mm Hg (PWP). In conclusion pressotherapy increases RAP and pulmonary pressures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212871 TI - [A survey of the French-speaking Association of Lymphology on the use of pressotherapy in France during the treatment of lymphedema]. AB - 116 physicians out of the 1000 who were questioned use pressure-therapy in the treatment of lymphedema of the extremities. Another 170 are interested in the technique and await this report before possibly adopting it. Overall, the devices utilized are compartmented and use discontinued pressure that is asynchronous in relations to heart beat; each session lasts 30 minutes, on average, with compression and resting phases lasting 45 seconds and 15 seconds, respectively. The usual schedule is one session daily, three days per week, in two series clustered within a single year. Although manual drainage of lymphatics is combined with pressure-therapy in 71.55% of the times, only 43.47% of physicians use elastic support following the treatment. Results are good or very good in 64.4% of cases, and the incidence of post-therapeutic events is rather low (polyuria, pain recrudescence of lymphangitis, etc.). Aside from lymphedema, venous insufficiency, hypodermitis and leg ulcers may also benefit from pressure therapy. PMID- 2212872 TI - [Mercury pressotherapy in the treatment of lymphedema]. AB - Increasingly growing pressure gradients impressed upon a limb maintained vertically positioned in mercury (metal) have been used as an individually adjusted compressive, evacuating and atraumatic mould in lymphatic or venolymphatic disease of the limbs. We studied this new so-called mercury pressure-therapy applied to 100 cases of lymphedema of the upper extremity, 100 cases of lymphedema of the lower extremity, 150 cases of inflammatory hypodermitis of the leg and 50 refractory venous ulcers. During the first trials, the patients were treated with a prototype, then with a model of the latest version of the Gradient-1000 device (fig. 1), allowing for mercury displacement along the limb controllable by 6 parameters. During experimentation, we used the following methodology: 1) Each patient's treatment consisted in 3 to 4 compression sessions at 3 to 8 day intervals. Later, the patient was followed up for 3 to 6 months and received 1 to 2 additional pressure treatments, as deemed necessary. 2) Each session comprised 30 minutes of actual compression by several rising mercury waves falling back to the zero level each time, using the following criteria: slow velocities (1 to 2 cm/second), progressively higher rising levels (45 to 70, even 80 cm), each level upheld for 3 to 5 minutes, few repeated up and down phases (6 to 10, depending upon the duration of each phase). 3) In between the compression sessions, the patient wore a compressive elastic bandage permanently. 4) The first 3 to 4 compression sessions constituted the initial treatment; the patient was then fit with a removable elastic bandage to be worn 12/24 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212874 TI - [Hydrotherapy in pressotherapy]. PMID- 2212873 TI - [Bandage technics in lymphedema of the extremities]. PMID- 2212875 TI - [Medical compression stockings in the treatment of lymphedema of the extremities]. PMID- 2212876 TI - [ A comparative lympho-scintigraphic evaluation of manual lymphatic drainage and pressotherapy in edema of the arm following treatment of a breast tumor]. AB - Manual lymphatic drainage (MLD) and pressure-therapy are part of the therapeutical gears used in physiotherapy for reducing edema. The solution to the problem of the reduction fo lymphedema of the extremities rests with the evacuation of the liquid phase and the resorption of the stagnant proteins in the interstitial compartment not being collected by the lymphatic system. The injection of a 99 Technetium-labelled colloid substance provides a functional approach to the problem of lymphatic stasis. PMID- 2212877 TI - [Conservative hospital treatment of lymphedema of the extremities]. PMID- 2212878 TI - [Hemorheologic changes in patients with obliterative arteriopathy of the leg before and after muscle exercise tests]. AB - Blood and plasma viscosity, erythrocyte filtrability and blood gas analysis were determined in 25 subjects with arteriosclerosis obliterans of the lower limbs before and after a muscle exercise test. Thirty-six shear rates between 0 and 230 s1 were studied to obtain viscosity curves, and regression analysis was performed for each curve. Mean viscosity curves for pathologic and control populations were plotted. The purpose of the study was to determine whether viscosity curves for blood and plasma before and after exercise, based on a high number of measurements, can provide information on rheological changes during intermittent claudication. Practically all viscosity curves in pathologic and control subjects could be described using a hyperbolic equation. Plasma as well as blood viscosity increased in pathologic subjects after exercise. However, erythrocyte filtrability and blood gas analysis in pathologic and control subjects, and blood and plasma viscosity in control subjects, showed no statistically significant changes after exercise. It is suggested that muscle exercise in reduced blood flow conditions can alter the aggregation of macromolecular complexes of plasma proteins, which could have an influence on cell components by modifying blood rheological behavior during claudication. PMID- 2212879 TI - [The effect of vascular risk factors in arteriopathy of the legs in women]. AB - Here the analysis of the results of a multicentered prospective epidemiologic study that has counted only the new cases of chronic atherosclerosis obliterans of the lower extremities. Included have been 989 patients (659 men and 330 women). Critical analysis of data allows a comparative study between the sexes. Thus, specifics of arteriopathy among women can be drawn. It appears that they are only the consequences of the fact that men and women reflect a different level of tobacco use in the two populations. PMID- 2212880 TI - [Isolated stenosis of the popliteal artery after treatment with methysergide. An anatomopathologic study]. AB - One case of isolate stenosis of the popliteal artery in a young woman is reported in this article. Since acid Methysergide maleate had been taken over a longer period, this lesion was placed into the nosological context of toxic arterial fibrodysplasia. Although such lesions usually recede at the end of treatment, the severity and abruptness of ischemia in this case led to operating the patient. This allowed an anatomopathological examination, which showed the diffusion of fibrosis into all layers of the arterial wall. PMID- 2212881 TI - Power spectral and microvector frequency analysis of dynamic standing foot force patterns in a normal male subject. AB - Power spectral and microvector frequency analyses of dynamic standing foot force patterns in a normal male subject were performed using a multiple-trial experimental protocol. Power spectral analysis of eight eyes-open vs. eyes-closed 50-sec trials revealed significant power increases in the 0.14 to 0.66 Hz range with eye closure, which were repeatable in trials performed on the same subject 2 wk later. Since power spectral differences are difficult to interpret biomechanically, a (micro)vector analysis of 1/20 sec changes in proportional weight transfer was employed. This methodology was able to reveal that foot force weight transfer exhibited a distinct preferred directionality, and that the eyes closed condition was characterized by significant increases in both the occurrence and average magnitudes of these preferred microvectors. PMID- 2212882 TI - Analysis of dynamic standing foot force patterns in a normal male subject by characterization of microvector weight transfer sequences. AB - Previous foot forceplate analyses in our laboratory have shown that postural sway in a normal male subject induces net weight transfers (microvectors) which have preferred directionalities, and that eye closure is characterized by increases in both the occurrence and magnitudes of these preferred microvectors. The same data generated from 8 x 8 blocks of eyes-open and eyes-closed trials were reanalyzed to examine microvector temporal sequences (i.e., macrovectors). Macrovectors were defined by the number of successive microvectors occurring along the same general direction, (anterior, posterior, right or left). Results suggest that with eye closure, proprioceptive systems are unable to maintain lateral sway deviations within eyes-open limits. This instability increases lateral macrovector durations while only marginally affecting sagittal macrovector durations. PMID- 2212883 TI - The physics of spinal manipulation. Part IV. A theoretical consideration of the physician impact force and energy requirements needed to produce synovial joint cavitation. AB - The critical force and energy required to facilitate synovial joint cavitation are presented as functions of seven parameters: joint and patient stiffnesses, joint and patient elasticities, the proportion of impacting energy entering the joint and patient, and the critical joint distraction at which cavitation occurs. These parameters are governed by numerous properties of the patient, doctor, joint, and the adjustive process. Equations for the critical force and energy are derived and the seven parameters and their governing factors are discussed. PMID- 2212884 TI - The superior intracapsular ligament of the sacroiliac joint: presumptive evidence for confirmation of Illi's ligament. AB - The existence of a superior intracapsular ligament within the sacroiliac joint has been disputed for years. This study notes that the dissection technique used to open the sacroiliac joint is of critical importance in finding this ligament. A dissection technique that emphasizes an inferior approach to the joint cavity is described. A superior intracapsular ligament of the sacroiliac joint (Illi's ligament) is noted with a 75% frequency in dissected cadavers. Illi's model for motion of the sacrum was based partially on the function of this ligament. The findings of this study suggest that current models of motion at the sacroiliac joint must include the presence of a superior intracapsular ligament. PMID- 2212885 TI - Skeletal applications of videofluoroscopy. AB - The use of skeletal videofluoroscopy is spreading as new applications emerge for coupling the fluoroscope with the video cassette recorder to obtain detailed information on moving anatomy. This review compiles the findings of an extensive literature search and summarizes the current state of videofluoroscopy knowledge. It traces the development of this imaging tool, beginning with cineradiography and its early investigations into cervical spine motion in the 1950s. Videofluoroscopy is presently used to evaluate the entire spine and other areas of the skeletal system, as well as diverse systems throughout the body. Because it is the only imaging technique capable of visualizing actual joint motion in real time, it provides details on movement mechanics not available through other methods. Along with presenting current applications of videofluoroscopy, this review points to future research needs. PMID- 2212886 TI - Mechanically induced pelvic pain and organic dysfunction in a patient without low back pain. AB - Previous reports have identified mechanical disorders of the lumbar spine as a cause of pelvic pain and organic dysfunction (PPOD) in patients with low back pain. Less common however, are reports of mechanically induced pelvic pain and organic dysfunction in patients without accompanying low back pain. This report details the examination findings and treatment response of a patient with pelvic pain, organic dysfunction and clinical evidence of lower sacral nerve root compression (LSNRC) in whom low back pain was not an accompanying finding. Despite the absence of low back pain however, clinical evaluation revealed the characteristic findings of mechanically induced pelvic pain and organic dysfunction secondary to lower sacral nerve root irritation or compression as a result of a mechanical disorder of the low back. As in long standing cases of mechanically induced pelvic pain and organic dysfunction in which low back pain is present, this case also exhibited severe and widespread involvement of the pelvic organs. In spite of numerous failed attempts at treatment directed at the symptomatic component of the patients disorder, complete resolution of symptoms was achieved by manipulative treatment directed at the mechanical disorder of the lumbar spine. PMID- 2212887 TI - Is there a chiropractic science? PMID- 2212888 TI - Effect of unilateral spinal adjustments on goniometrically-assessed cervical lateral-flexion end-range asymmetries in otherwise asymptomatic subjects. PMID- 2212889 TI - Manual therapy considerations at the thoracolumbar junction: an anatomical and functional perspective. PMID- 2212890 TI - Lumpectomy and radiation therapy for breast cancer. PMID- 2212891 TI - The hospital/physician relationship: a look at some fundamentals. PMID- 2212892 TI - Testimony on rural hospitals. PMID- 2212893 TI - Hospitals pay dearly for government underfunding. PMID- 2212894 TI - Hospitals support plan to reduce the number of uninsured Georgians. PMID- 2212895 TI - Health care reform: cultivating a national consensus. PMID- 2212896 TI - What physicians owe hospitals: an overview. PMID- 2212897 TI - What physicians owe hospitals: an administrator's view. PMID- 2212898 TI - What hospitals owe physicians: a CEO's view. PMID- 2212899 TI - What hospitals owe physicians: a trustee's view. PMID- 2212900 TI - What physicians owe hospitals: an individual practitioner's view. PMID- 2212901 TI - MAG adopts Model Medical Staff Bylaws. PMID- 2212903 TI - Untimely diagnosis of breast cancer--everyone loses. PMID- 2212902 TI - The current status of coronary artery balloon angioplasty. PMID- 2212904 TI - Medicaid voluntary contribution program begins. PMID- 2212905 TI - Ruptured gastric artery aneurysm complicating pneumococcal sepsis: a case report and review. PMID- 2212906 TI - Clinical aspects of lumbar intervertebral disc disease. AB - The diagnosis and management of lumbar disc disease has undergone significant changes in recent years. This is especially true for diagnostic imaging studies (MRI and CT). Currently, CT/myelography or unenhanced MRI may be used to confirm the diagnosis and the level of involvement of lumbar disc disease. The indications for lumbar disc surgery include patients with neurologic deficits and/or those in whom intractable pain does not respond to conservative measures. Conventional disc surgery and/or microdiscectomy are both good operative procedures for lumbar disc disease, and each yields excellent results when criteria for diagnosis and surgery are strictly followed. PMID- 2212907 TI - Dominique-Jean Larrey: Napoleon's surgeon from Egypt to Waterloo. PMID- 2212908 TI - New techniques for percutaneous coronary artery revascularization. PMID- 2212909 TI - Advance medical directives: durable power of attorney for Health Care Act. PMID- 2212910 TI - Comparative study of vanillylmandelic acid in random and 24-hour urine collections. AB - Urinary vanillylmandelic acid (VMA) levels were determined in random samples and in 24-hour collections from 52 patients. Random sample levels were compared with levels in 24-hour collections and showed good correlation (r = 0.99), and no statistically significant differences was found when urinary VMA levels in random samples expressed in micrograms/mg creatinine (p greater than 0.1). Normal values of VMA in random urine samples of 226 healthy volunteers for different age groups of 1-5, 6-10, 11-15, 16-30, 31-60 years old were 17.03 +/- 6.61, 10.32 +/- 3.25, 10.87 +/- 4.5, 7.62 +/- 3.05 and 7.79 +/- 3.94 micrograms/mg of creatinine respectively. PMID- 2212911 TI - The association of adenosine deaminase activity with T-lymphocytes and subsets in pulmonary tuberculosis and bronchogenic carcinoma. AB - Simultaneous determination of blood/lung ADA activity and T-lymphocyte subsets was conducted in 12 patients with active pulmonary tuberculosis, 12 patients with bronchogenic carcinoma and 11 healthy volunteers. Differences were significant only in the tuberculosis patients, namely, increased mean enzyme values in both the peripheral blood (36.68 +/- 10.90 U/L) and in the BALF (4.25 +/- 2.19 U/L), and correlation of ADA activity between the blood and the diseased lung only; the difference in elevated enzymatic activity between the tuberculosis group and the cancer group was of no statistical significance. We conclude that simultaneous ADA analysis of the blood and the BALF may be of diagnostic value in cases suspected of having tuberculosis as yet undiagnosed by other means. Based on the lowest value of enzymatic activity in the blood of patients with tuberculosis (28 U/L), the test has a sensitivity of 75 per cent and a specificity of 100 per cent; whereas the lowest value in the BALF of tuberculosis patients (2.9 U/L), the test has a sensitivity of 77 per cent and a specificity of 82 per cent. Findings that there was a blood-lung correlation of elevated ADA activity and a correlation of enzymatic elevation with increased numbers of T-cells bearing IL-2 receptor in cases of pulmonary tuberculosis only provide evidence in support of T lymphocytes actively participating in the ongoing immune process. PMID- 2212912 TI - Oxygen desaturation induced by bronchoalveolar lavage. AB - Our study demonstrates that bronchoalveolar lavage can induce significant desaturation in patients with a resting PaO2 of below 70 torr, and that supplemental oxygen at 5 L/min through a nasal cannula may not prevent a marked drop in the oxygen saturation during this procedure. Therefore, measures to provide higher FiO2 should be offered to assure adequate oxygenation in severely ill patients requiring bronchoalveolar lavage. PMID- 2212913 TI - Sensorineural hearing loss in children recovered from purulent meningitis: a study in Thai children at Ramathibodi Hospital. AB - Hearing loss is one of the serious complications of bacterial meningitis. Conventional audiometry and auditory brainstem response (ABR) methods were used to detect this complication in eighteen children who recovered from bacterial meningitis treated at Ramathibodi Hospital from January 1983 to December 1987. Six patients (33%) were found to have persistent bilateral sensorineural hearing loss. Among them, the causes of meningitis were: Hemophilus influenzae (3 patients), Streptococcus pneumoniae (1 patient), Streptococcus agalactiae (1 patient) and Escherichia coli (1 patient). Various clinical and demographic factors were examined in relation to the hearing loss, but no significant correlation was observed. Since meningitis often affects small children and makes conventional audiometry tests difficult, ABR was found to be a more effective method for testing this group of patients. PMID- 2212915 TI - Liver abscess: a clinical study of 222 patients. AB - The medical records of 222 patients with liver abscess at Siriraj Hospital from 1978 to 1985 were analysed. Amoebic abscess was three times more prevalent than pyogenic abscess. In both groups middle aged males were affected more often than others. The main clinical manifestations were fever, right upper quadrant pain and hepatomegaly. History of colitis in the past, marked leukocytosis, elevation of alkaline phosphatase and a single abscess confined to the right lobe were suggestive of amoebic liver abscess. The presence of concurrent abdominal infection, marked anemia and jaundice were associated with pyogenic abscess. Patients with pyogenic abscess developed complications more often and the case fatality rate was greater than patients with amoebic abscess. Most of the patients were successfully treated with a combination of antimicrobials and drainage. PMID- 2212916 TI - Cutaneous leukocytoclastic vasculitis: clinical and laboratory features of 45 patients seen in Ramathibodi Hospital. AB - Forty-five patients with histologically proved cutaneous leukocytoclastic vasculitis were studied with regard to the clinical features, laboratory findings and etiology. There were 12 males and 33 females, with an age range of 13 to 64 years. The most common skin lesions were palpable purpura which appeared mostly on the lower part of the legs. Renal involvement was the most common systemic manifestation, which occurred in 45 per cent of the patients. Abdominal pain occurred in 42 per cent of the male patients while none of the female patients had this symptom. Arthralgia occurred in 20 per cent of the patients. The most common laboratory abnormalities were elevation of ESR, which was significantly more common in females than in males (P = 0.047). The possible etiology of leukocytoclastic vasculitis was identified in 5 patients, these included streptococcal infection in 2 patients, in the other patients the possible causes were penicillin hypersensitivity, systemic lupus erythematosus and livedoid vasculitis, respectively. PMID- 2212914 TI - Oxygen desaturation during fibreoptic bronchoscopy. AB - One hundred consecutive patients, who underwent bronchoscopic examination for diagnostic purposes, were studied with regard to various aspects of possible SaO2 deterioration. Relevant findings are as follows: (1) The pulse oximeter is as good as the conventional blood gas analyser for quantitating SaO2; (2) oxygen desaturation in the range of 1 to 25 per cent (median 5, mean 5.6 +/- 4) occurred in approximately 97 per cent of the bronchoscopy examinees; recuperation time of SaO2 was 1 to 34 minutes (median 6, mean 8.2 +/- 6.5); (3) the factor aggravating desaturation included the examination of patients in the sitting position; the fact that bronchial washing was connected with greater SaO2 deterioration in the non-hypoxaemic group of patients needs further investigation with regard to its role in the mechanism of oxygen desaturation; (4) the amount of fluid instilled intra-tracheally, bronchial biopsy and duration of the procedure were not related to the decline in SaO2. Based on the results of the present study, the authors suggest that all procedures ought to be performed on patients undergoing examination in the supine position, and that the patients should be supplemented with low-flow oxygen. PMID- 2212917 TI - Thoracolumbar burst fracture with another spinal fracture. AB - From January 1985 to May 1988, thirty-six patients with thoracolumbar burst fracture were treated and nine of these (25%) were associated with another burst fracture or wedge compression fracture. The etiology of injury was a fall from a height in four patients, motorcycle accident in three, and elevator crushing and house crushing in each of the other two patients respectively. The neurological implications were caused by the main burst fractures, and L1 was the most involved segment of the main burst fracture (44.4%). All three patients had associated wedge compression fracture, as well as three patients who had associated burst fracture, found adjacent to the main burst fracture. The remaining three associated burst fractures were found at a distant level to the main burst fracture. PMID- 2212918 TI - Seven day metronidazole versus single dose tinidazole as therapy for nonspecific vaginitis. AB - A comparative study of the treatment of nonspecific vaginitis was carried out in 171 reproductive-aged women. The patients were randomly treated with either metronidazole or tinidazole (Ninety-three patients in Group I, received oral metronidazole 1 g daily for 7 days. Another 78 patients in Group II, received oral tinidazole 2 g single dose. The patients were advised to return for follow up examinations 1-2 weeks after treatment in their nonmenstrual period. Of these, 50 patients in each group were subject to complete study. The cure rates were 92 per cent in Group I and 86 per cent in Group II. The difference was not significant statistically. The adverse drug reactions among the two groups were 22 and 8 per cent respectively. Tinidazole is another effective drug for the treatment of nonspecific vaginitis. PMID- 2212919 TI - Maffucci's syndrome with frontal lobe astrocytoma. AB - Maffucci's syndrome is a particularly rare clinical form of mesodermal dysplasia. It consists of angiomatosis, chondromatosis and sometimes dyschromic cutaneous lesions. The syndrome is usually associated with a high incidence of malignancy, originating primarily from mesodermal derivatives. The present case is the second in the literature in which the syndrome is associated with a frontal lobe astrocytoma. This patient and those reported in the literature, suggest the potential involvement of non-mesodermal tumors in the Maffucci's syndrome. PMID- 2212920 TI - Sertoli-cell-only syndrome: a case report. AB - A 20-year-old male presented with a small hydrocoele in the left scrotal sac, bilateral small testes, and azoospermia with normal secondary sexual characteristics. Chromosome study revealed 46,XY. The results of hormonal and histopathological studies were consistent with Sertoli-cell-only syndrome. PMID- 2212921 TI - Morphological and antigenic variations of human T cell leukemia virus type I particles in human lymphocytes. AB - HTLV-I particles grown in 4 human lymphocyte cultures were observed by electron microscopy. Particles in all cell lines showed marked size and structural variations that were characteristic of each cell line. Profiles of size distributions were found to be similar among virus particles of the same origin in different cell lines. Immunogold electron microscopy using monoclonal antibody to HTLV-I-p15, -p19, or -p24 revealed varying reactivities of individual particles. By double-labeling technique using antibody to HTLV-I-p19 or -p24, particles were found to be classifiable into 4 groups: p19+p24+, p19+p24-, p19 p24%, and p19-p24-. Each cell line showed the characteristic profile of distributions of virus particles of each group as observed at different in vitro passage levels. These antibodies reacted with certain structures in the extracellular space and in the cytoplasm. Results of this study demonstrate variations in morphology and antigenicity, as well as the morphogenesis of HTLV-I particles in different host cells. PMID- 2212922 TI - Immunocytochemical evaluation of Trichinella spiralis larval antigen. AB - The antigenicity of Trichinella spiralis muscle larvae was studied for the purpose of developing an immunodiagnostic test for trichinosis. Ultrathin sections of fixed larvae were treated with sera from patients with a variety of parasitic infections including trichinosis, anisakiasis, gnathostomiasis, fascioliasis, dirofilariasis, severe trichuriasis, moderate trichuriasis, paragonimiasis, cysticercosis cellulosae hominis and diphyllobothriasis, and then treated with protein A-tagged colloidal gold. The cuticle surface and stichocyte alpha 0- and alpha 1-granules reacted predominantly with sera from trichinosis and severe trichuriasis patients, and negligibly with the others. By contrast, the cuticle inner layer, hypodermis, and hemolymph reacted with all sera examined though there was some variability in the intensity of the staining. These results suggest that the cuticle surface and stichocyte alpha-granules possess a high degree of specificity for antibody-produced in T. spiralis infection, whereas the other larval components exhibit nonspecificity. PMID- 2212923 TI - Ultrastructure of a water-clear cell in the golden hamster parathyroid gland. AB - A new type of cell was observed in the parathyroid gland of the golden hamster. The cell contained numerous vacuoles and resembled the water-clear cell. The fine structure of the vacuolated cell was described and discussed. PMID- 2212924 TI - Membranous body in the jejunal absorptive cells of suckling rat intestine. AB - In the jejunal absorptive cells of suckling rats, a distinctive membranous body was found in their lateral cytoplasm and the Golgi region. This organelle was ovoid in contour (1 to 2 microns in diameter) and consisted of highly convoluted cisternae of a rough endoplasmic reticulum (RER). The individual cisternae were round (approximately 55 nm in diameter) with variable electron-dense content and separated by uniformly narrow channels (approximately 25 nm in width) which were continuous to the cytoplasmic matrix. In a proper section, the cisternae arranged in an approximately hexagonal pattern, and one of the cisternae was seen occupying the center of the hexagon. The membranous body was in continuity at its margin with the cisternae of a smooth endoplasmic reticulum (SER), and with the dilated cisternae which often contain chylomicron lipid droplets. It is possible that this structure serves as a kind of "reservoir" of the SER membranes for the lipid synthesis of the jejunal absorptive cells. PMID- 2212925 TI - Three-dimensional meshwork structure of glomerular basement membrane revealed by chemical treatment. AB - In order to study the three-dimensional ultrastructure of the glomerular basement membrane (GBM), isolated GBM was treated with elastase, sodium dodecyl sulfate, and 2-mercaptoethanol and examined by transmission electron microscopy using ultrathin sectioning method and stereoscopic view. This treatment revealed clearly three-dimensional meshwork structure of GBM mainly composed of type IV collagen. Numerous regular polygonal small pores were present in the meshwork structure. The average short dimension of the small pores was 4.1 +/- 1.8 nm and the average long dimension was 4.8 +/- 2.2 nm. Our present results further support the molecular sieve theory of the basement membrane. PMID- 2212926 TI - Molecular evidence for the presence of growth hormone receptors in the bovine mammary gland. AB - GH receptor messenger RNA (mRNA) was identified and characterized in mammary tissue from normal and GH-treated lactating cows using Northern and in-situ hybridization analyses. One major GH receptor transcript of 4.4 kilobases and a less abundant transcript of 9.2 kilobases were detected in mammary tissue from both normal and GH-treated cows. In-situ hybridization analysis revealed that the GH receptor gene is primarily expressed in the alveolar epithelial cells of mammary tissue. These results are evidence that the lactating mammary gland may synthesize GH receptors. On the basis of these observations it seems likely that the lactating bovine mammary gland is a GH target tissue. This finding challenges the widely accepted view that GH does not directly regulate mammary growth or function. PMID- 2212927 TI - Local hormones in the kidney: protectors of the kidney against the body? PMID- 2212928 TI - Influence of mating and intra-uterine oestradiol infusion on peripheral oxytocin concentrations in the sow. AB - Oxytocin concentrations were measured radioimmunologically in sows on the day of standing oestrus over a 6-h period (controls, n = 6) or 1 h before and 5 h after mating (n = 5) or transcervical infusion of either 100 ml saline (0.9% (w/v) NaCl, n = 7) or saline plus 10 micrograms oestradiol (simulation of seminal oestrogens, n = 5). In the controls, oxytocin was low, at around 1.0 pmol/l, throughout the investigation period. Similarly, saline infusion did not lead to a noticeable change in oxytocin concentrations in six out of seven sows. In one sow, however, infusion led to a maximum of 86 pmol/l at 1 min after infusion. Oestradiol led to no immediate increase in oxytocin concentrations. Later in the post-treatment period (2-5 h) they were only slightly increased (1 pmol/l vs 3 pmol/l). All mated sows reacted with a rapid and clear increase in oxytocin. Maximal concentrations (42.0 +/- 5.1 pmol/l; mean +/- S.E.M.) appeared 2 min after the onset of ejaculation. Clearly increased concentrations were found for 40 min. It was concluded that mating specifically leads to a rise in oxytocin, probably due to both mechanical and pheromonal stimuli provided by the boar. PMID- 2212929 TI - Effects of hypophysectomy and human chorionic gonadotrophin on Leydig cell function in mature rats. AB - The biochemical activities involved in the maintenance of Leydig cell functions, and the effects of hypophysectomy and human chorionic gonadotrophin (hCG) on these functions are largely unknown. In the present study, adult hypophysectomized rats were used as a model to determine the effects of these treatments on a number of biochemical and morphological parameters. After 33 days of hypophysectomy, the morphology of the Leydig cells had been drastically altered. In addition, alpha-naphthol and beta-naphthol esterase activity as well as the steroidogenic capacity of the Leydig cells were greatly reduced at this time. In contrast, the level of sterol carrier protein 2 (SCP2), a Leydig cell specific protein, was affected by hypophysectomy much less than the other parameters measured. Two daily injections of hCG to rats hypophysectomized for 31 days resulted in no change in the morphology of the Leydig cells, or in their proliferative activity. Non-specific esterase activities were also unaffected by 2 days of treatment with hCG. However, two injections of hCG to rats hypophysectomized for 31 days resulted in nearly complete restoration of steroidogenic capacity, and a 3.5-fold increase in the level of SCP2. These findings indicate that hypophysectomy results in significant morphological and biochemical changes in Leydig cells, and that hCG is capable of restoring some of these capacities within a short time. PMID- 2212930 TI - Evidence that desensitization of the negative feedback of oestrogen and priming for the positive feedback of oestrogen depend upon a common mechanism of oestrogen action in rats. AB - Oestrogen priming of the central nervous system is required for the positive feedback of oestrogen, and the sensitivity of the negative feedback of oestrogen can be reduced by oestrogen itself. Using adult female and male rats we examined the possibility that these effects depend upon a common mechanism of oestrogen action that is mediated by the medial preoptic area (MPOA). Guide cannulae were implanted in the MPOA of 4-day cyclic rats which were ovariectomized during the evening of day 1 of dioestrus. Glass capillary tubes containing different substances were placed in the cannulae between 09.00 and 12.00 h on the presumptive day 2 of dioestrus. The effectiveness of oestrogen priming was evaluated by examining whether an s.c. implant of oestradiol-17 beta (OE2) induced an LH surge, and the inhibitory effect of oestrogen on tonic LH secretion was investigated by injecting the rats with 3 micrograms oestradiol benzoate (OB)/100 g body weight. The priming effect of an s.c. implant of OE2 could be imitated by the bilateral implantation in the MPOA of a mixture of OB and cholesterol at a ratio of 1:360 for 3 h only. Similar medial preoptic oestrogen implantation also significantly reduced the LH-inhibiting effect of OB. In accord with findings obtained in former studies on desensitization of the negative oestrogen feedback, oestrogen priming resulting from the s.c. administration of OE2 could be suppressed by short-term medial preoptic implantation of clomiphene citrate or apomorphine; bilateral electrical stimulation of the medial amygdaloid nucleus induced an increase in the serum concentration of LH in ovariectomized females implanted with OB in the MPOA, but not in castrated males pretreated and implanted with OB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212932 TI - Nuclear tri-iodothyronine (T3) binding in neonatal rat brain suggests a direct glial requirement for T3 during development. AB - Tri-iodothyronine (T3) binding studies were performed on neuronal and glial nuclei prepared from developing rats brain by discontinuous sucrose gradient centrifugation. Maximum binding capacities (MBC) and dissociation constants (Kd) were obtained from Eadie-Hofstee plots of transformed data. An ontogenic study on nuclei prepared from whole brain revealed that on day 5 after birth, glial nuclear MBC was 1774 +/- 201 (S.E.M.) fmol/mg DNA compared with 974 +/- 117 fmol/mg DNA for the neurones (P less than 0.01). Although diminishing to 667 +/- 112 fmol/mg DNA by day 21, alterations in neuronal MBC over the neonatal period were not statistically significant, whereas glial MBC diminished steadily to 557 +/- 133 fmol/mg DNA in glial nuclei (P less than 0.05). Over the same period, a significant reduction in Kd was noted only in the glia, from 3.17 +/- 0.40 to 1.83 +/- 0.34 nmol/l (P less than 0.03). Ligand specificity of the receptor in both nuclear types on day 21 was tri-iodoacetic acid greater than T3 greater than thyroxine greater than 3,3',5'-T3, but this was less clearly demonstrated at day 5. Regional studies on days 15 and 21 demonstrated that for both neuronal and glial nuclei, receptors are concentrated in the cerebral cortex and diminish in a cranio-caudal direction. Cerebral glial MBC on day 21 was 2215 +/- 147 fmol/mg DNA, at this stage still exceeding the cerebral neuronal capacity of 1111 +/- 207 fmol/mg DNA. The results indicate that neonatal glia may respond directly to thyroid hormones via nuclear receptor binding, and that receptors are predominantly located in the cortex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212931 TI - Comparison of the effects of parathyroid hormone (PTH) and recombinant PTH related protein on bicarbonate excretion by the isolated perfused rat kidney. AB - The isolated perfused rat kidney was used to study the effects of amino-terminal fragments of human parathyroid hormone, hPTH(1-34), bovine parathyroid hormone, bPTH(1-84) and of PTH-related proteins, PTHrP(1-34), PTHrP(1-84), PTHrP(1-108) and PTHrP(1-141) on urinary bicarbonate excretion. PTHrP(1-34) (7 nmol/l), bPTH(1 84) (5.5 nmol/l) and hPTH(1-34) (7 nmol/l) had similar effects in increasing bicarbonate excretion with respect to the control. At lower concentrations (0.7 nmol/l) all PTHrP components, but not hPTH(1-34) or bPTH(1-84) increased bicarbonate excretion significantly. Infusions of PTHrP(1-108) and PTHrP(1-141) at 0.7 nmol/l, while associated with a rise in urinary bicarbonate concentration and excretion during the early stages of perfusion, produced a sharp decline in bicarbonate concentration and excretion in the latter part of perfusion. The different peptides produced no significant differences in glomerular filtration rate, fractional excretion of sodium or urine volume. The absence of substantial differences between the effects of hPTH(1-34) and PTHrP(1-34) are as noted in previous studies. The differences between PTHrP(1-108)/PTHrP(1-141) and PTHrP(1 34) demonstrated here are consistent with (1) the clinical manifestations of acidosis in hyperparathyroidism and alkalosis in humoral hypercalcaemia of malignancy, and (2) an independent action of a component of PTHrP beyond amino acids 1-34. PMID- 2212933 TI - Influence of oestrogen and progesterone on macrophage distribution in the mouse uterus. AB - Macrophages are constituents of all normal connective tissue including the murine uterus. Macrophages have been identified previously in endometrium and myometrium of pregnant and non-pregnant murine uterus using antibodies against macrophages. In the current study immunohistochemical analysis of murine uterus demonstrated that there were not significant quantitative differences in uterine macrophages between the diestrous, pro-oestrous and oestrous stages. However, distributional changes occurred during the oestrous cycle. Macrophages were evenly distributed throughout uterine tissue during dioestrus, while, during pro-oestrus and oestrus, their concentration was highest in the subepithelial stroma. Because the oestrous cycle is hormonally regulated, we asked whether or not oestrogen and/or progesterone might influence macrophage distribution. Ovariectomy, which eliminates cyclical production of oestrogen and progesterone, resulted in a significant decrease in both the relative and the absolute number of uterine macrophages within 6 days. Injections of progesterone or oestrogen to ovariectomized mice resulted in restoration of uterine macrophage numbers. Injection of oestrogen plus progesterone in a regimen known to prepare the uterus for receptivity for blastocyst implantation increased the number of macrophages to levels which were consistently higher than those seen during oestrus. Moreover, following hormone administration macrophages were more concentrated in the subepithelial stroma, a distributional pattern which was most evident following injection of both hormones. The results suggest that both oestrogen and progesterone promote quantitative and distributional changes in the uterine macrophage population. PMID- 2212934 TI - Islet amyloid polypeptide-like immunoreactivity (amylin) in rats treated with dexamethasone and streptozotocin. AB - Islet amyloid polypeptide (IAPP) is a 37 amino acid peptide present in pancreatic beta-cells. Pancreatic and circulating IAPP concentrations in rat models of diabetes were measured using a specific radioimmunoassay. Pancreatic IAPP-like immunoreactivity (IAPP-IR) in dexamethasone-treated rats was twice that of the control rats (1571 +/- 137 vs 657 +/- 176 (S.E.M.; n = 6) pmol/g), and this was reflected by similar changes in the plasma IAPP-IR (272 +/- 17 vs 102 +/- 10 pmol/l). In streptozotocin-treated rats, pancreatic IAPP-IR (200 +/- 90 pmol/g) was reduced compared with controls. There was a significant positive correlation between pancreatic and plasma IAPP-IR and insulin, with r values of 0.82 and 0.91 for the plasma and pancreas respectively. Characterization of pancreatic immunoreactivity, using gel chromatography, revealed two peaks of IAPP-IR, one which coeluted with synthetic human amidated IAPP and another peak, presumably a fragment or breakdown product, which eluted later. Chromatography of the plasma IAPP-IR revealed that greater than 90% of the IAPP-IR eluted in the void volume, although the remaining IR coeluted with the synthetic IAPP standard. These results are not straightforwardly compatible with the suggested role for IAPP as a hormonal, paracrine or autocrine inhibitory regulator of insulin secretion in the maintenance of carbohydrate homeostasis. PMID- 2212935 TI - Increase in milk secretion and mammary blood flow by intra-arterial infusion of insulin-like growth factor-I into the mammary gland of the goat. AB - The close-arterial infusion of free insulin-like growth factor-I (IGF-I; 1.1 nmol/min) for 6 h into the pudic artery supplying one mammary gland of lactating goats caused a 25 +/- 6% (mean +/- S.E.M., n = 6) increase in the rate of milk secretion of that gland. The increase in the rate of milk secretion in the adjacent noninfused gland (14 +/- 4%) was not significantly different from that observed during saline infusion (4 +/- 5%). Blood flow to the infused gland was increased from 378 +/- 26 ml/min 1 h before to 487 +/- 56 ml/min approximately 5 h after the start of the infusion of IGF-I, declining to 420 +/- 44 ml/min approximately 2 h after the end of the infusion. The total concentration of IGF-I (free and bound) in milk of the infused gland was significantly higher than that of the non-infused gland. The concentrations of IGF-I in carotid arterial plasma samples increased during IGF-I infusion from a mean value of 32 +/- 2 nmol/l before to a maximum of 49 +/- 3 nmol/l 5 h after the infusion commenced. Circulating concentrations of total IGF-I declined slowly after the infusion with an estimated half-life of 5 h. Infusion of saline alone did not alter mammary blood flow or the concentration of total IGF-I in milk or plasma. The results indicate that the infusion of free IGF-I into the mammary arterial supply enhances milk secretion and mammary blood flow in intact, conscious goats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212936 TI - Localization of the growth hormone receptor/binding protein in skin. AB - Acromegaly is characterized by coarsening of facial features, acanthosis nigricans, hypertrichosis and oily skin. To determine the site through which GH exerts these effects, we have used immunohistochemistry to localize the GH receptor/binding protein (BP) in rat, rabbit and human skin. Three monoclonal antibodies (MAb 1, 43, 263) were immunoreactive in identical locations, whereas no immunoreactivity was evident when control monoclonal antibodies (MAb 50.8 and MAb 7 (rat] were used. Skin from neonatal and adult animals was used to determine whether GH receptor/BP expression was developmentally regulated. Immunoreactivity of the GH receptor/BP in the three species was consistently localized in the stratum basale and stratum spinosum. Intermittent staining was observed in the stratum granulosum. Scattered basal epidermal cells often displayed more intense immunoreactivity. This distribution was observed at all maturational stages examined. Intense GH receptor/BP immunoreactivity was observed in all histological layers of the lower one-third of hair follicles and in hair matrix cells of the dermal papillae. Immunoreactivity was also detected in the outer epithelial root sheath of the upper two-thirds of hair follicles, in sebaceous glands and in fibroblasts of the connective tissue sheath surrounding the follicle. GH receptor/BP immunoreactivity was also present in the secretory duct and myoepithelial cells of human eccrine sweat glands. Fibroblasts, Schwann cells of peripheral nerve fascicles, skeletal muscle cells and adipocytes of the dermis were also immunoreactive as were medial smooth muscle and endothelial cells of arteries. These results provide evidence that GH acts locally on the epidermis and epidermal appendages concordant with our recent localization of GH receptor/BP to epithelial cell types of the gastrointestinal and reproductive systems. PMID- 2212937 TI - Inhibin secretion during the ovulatory cycle and pregnancy in the common marmoset monkey. AB - Changes in plasma concentrations of immunoreactive inhibin in the reproductively cyclic, pregnant and ovariectomized female marmoset monkey (Callithrix jacchus) were measured with a heterologous radioimmunoassay. The pattern of inhibin secretion in five marmosets studied individually during four consecutive cycles was shown to resemble that of progesterone. In these animals, data were pooled according to stage of cycle on the basis of plasma progesterone concentrations. Mean values for inhibin were 5465 and 4972 U/l during the early and late follicular phase. Concentrations rose during the luteal phase to 8431, 12,246 and 12,557 U/l for the early, mid- and late luteal phase respectively. The hormonal profile of inhibin during the normal cycle is similar in both marmoset and stumptailed macaque; however, the marmoset has a 28-fold greater level of inhibin during the luteal phase. In six marmosets in which pregnancy occurred, inhibin concentrations showed no decline at the end of the conceptual cycle and remained increased with respect to the follicular phase throughout the subsequent gestation. Inhibin levels were non-detectable (less than 1000 U/l) in ovariectomized and acyclic marmosets. These results suggest that the corpus luteum is the major source of inhibin in this New World monkey, in common with man and the Old World primates. PMID- 2212938 TI - Ageing and the sensitivity of the adrenal gland to physiological doses of ACTH in man. AB - Healthy men and women aged 19-38 or 67-83, in whom endogenous ACTH secretion was suppressed with dexamethasone, were given successive injections of 60 ng, 150 ng and 250 micrograms ACTH(1-24) at hourly intervals, and blood samples for measurement of plasma cortisol were taken every 10 min. The response to each injection was taken as the increase in cortisol concentration 20 min later, when there was a peak with the lower doses, with allowance for disappearance of cortisol produced after the previous injection. On average, the responses to 60 and 150 ng ACTH were about 0.4 and 0.7 respectively of the response to 250 micrograms. There were no consistent effects of age or sex on any index of adrenocortical sensitivity or responsiveness, but some groups showed isolated differences from both their age- and sex-matched counterparts: the response to 60 ng ACTH was low in young men, maximal responsiveness was low in elderly men and the slope of the dose-response curve was high in elderly women. In most of the elderly subjects, plasma ACTH was determined separately under normal conditions. It was negatively correlated with the cortisol responses to 60 and 150 ng ACTH, suggesting that differences in adrenal sensitivity between subjects contribute to the variability of plasma ACTH. PMID- 2212939 TI - Reinfection results in accumulation of unintegrated viral DNA in cytopathic and persistent human immunodeficiency virus type 1 infection of CEM cells. AB - High levels of unintegrated viral DNA accumulate during human immunodeficiency virus type 1 (HIV-1) infection of CEM T cells. Reinfection of already infected cells is required to attain these levels and reinfection also promotes the development of HIV-induced cytopathology. Rates of virus production, however, are independent of the accumulation of unintegrated viral DNA. Neutralizing antibody added soon after infection reduced viral DNA levels without appreciably affecting the production of cell-free viral p24 antigen or reverse transcriptase activity. Only 50 pM AZT were required to reduce the accumulation of unintegrated viral DNA by 50% in contrast to the 25 nM required to inhibit virus production by 50%. Cytopathology, as measured by number of syncytia in infected cell cultures, was correlated with highly elevated levels of unintegrated viral DNA. The minimal levels of unintegrated viral DNA present constitutively in the persistently infected HCEM cell line were consonant with the absence of cytopathic effects in these cells. These data demonstrate that inhibiting the reinfection of already infected cells modulates cytopathic HIV-1 infection to a form that is persistent and noncytopathic. PMID- 2212940 TI - Genetic basis of viral persistence: single amino acid change in the viral glycoprotein affects ability of lymphocytic choriomeningitis virus to persist in adult mice. AB - This study has identified a single amino acid change in the viral glycoprotein that profoundly affects the ability of lymphocytic choriomeningitis virus (LCMV) to persist in its natural host. Adult immunocompetent mice infected with a variant of the Armstrong strain, spleen isolate clone 13 (svA/svA), harbor virus for several months and exhibit suppressed T cell responses. In contrast, adult mice infected with a reassortant virus (svA/wtA) that contains the L segment of the spleen variant and the S segment of the parental wt Armstrong, make potent LCMV-specific CTL responses and clear the infection within 2-4 wk. These two viruses, spleen variant clone 13 and the reassortant svA/wtA, are identical in their noncoding regions and show no amino acid changes in any of their viral genes except for one substitution in the glycoprotein. The reassortant virus svA/wtA has a phenylalanine at amino acid residue 260 of the glycoprotein, whereas the spleen variant clone 13 has a leucine at this position. This study constitutes one of the first reports defining the genetic basis of viral persistence at the whole animal level, and identifying a single mutation that markedly increases the ability of a virus to persist in its natural host. PMID- 2212941 TI - The autoantigen Ku is indistinguishable from NF IV, a protein forming multimeric protein-DNA complexes. AB - We have isolated a cDNA encoding the 84-kD subunit of NFIV. Tryptic peptide sequences were identified within the coding sequences, confirming its proper identity. The primary sequence of the protein is identical to that of the large subunit of the Ku autoantigen. A missing NFIV peptide sequence was identified within the sequence of the small subunit of Ku. In addition, the proteins are identical in immunological aspects. We suggest that the Ku and NFIV proteins are identical. This connection adds new biochemical data to our knowledge of the Ku autoantigen. PMID- 2212942 TI - Long-term human hematopoiesis in the SCID-hu mouse. AB - Coimplantation of small fragments of human fetal thymus and fetal liver into immunodeficient SCID mice resulted in the formation of a unique structure (Thy/Liv). Thereafter, the SCID-hu mice showed reproducible and long-term reconstitution of human hematopoietic activity. For periods lasting 5-11 mo after transplantation, active T lymphopoiesis was observed inside the grafts and cells that were negative for T cell markers were found to have colony-forming units for granulocyte/macrophage (CFU-GM) and erythroid burst-forming unit (BFU-E) activity in the methylcellulose colony assay. In addition, structures similar to normal human bone marrow were observed inside the Thy/Liv grafts, consisting of blast cells, mature and immature forms of myelomonocytic cells, and megakaryocytes. These data indicate long-term maintenance, in vivo, of human progenitor cells for the T lymphoid, myelomonocytic, erythroid, and megakaryocytic lineages. The role of the implanted fetal liver fragments was analyzed using HLA-mismatched Thy/Liv implants. The HLA type of the liver donor was found on T cells and macrophages in the graft. In addition, cells grown in the methylcellulose colony assay and cells in a bone marrow-like structure, the "thymic isle," expressed the HLA type of the liver donor. Thus, the Thy/Liv implants provided a microenvironment in which to follow human hematopoietic progenitor cells for multiple lineages. The formation of the Thy/Liv structures also results in a continuous source of human T cells in the peripheral circulation of the SCID-hu mouse. Though present for 5-11 mo, these cells did not engage in a xenograft (graft-versus-host) reaction. This animal model, the first in which multilineage human hematopoietic activity is maintained for long periods of time, should be useful for the analysis of human hematopoiesis in vivo. PMID- 2212943 TI - T cell target 1 (TCT.1): a novel target molecule for human non-major histocompatibility complex-restricted T lymphocytes. AB - We have studied two gamma/delta T cell clones, E102 and E117, generated in a mixed lymphocyte culture using an allogeneic Epstein-Barr virus-transformed B cell line, E418. These clones were both found to express a molecular form of T cell receptor (TCR) infrequent in human peripheral blood, associating a V1-J1-C delta chain and a V3-JP2-C2 gamma chain. Functionally, they appeared as cytotoxic T lymphocytes (CTL) with non-major histocompatibility complex (MHC) (class I and II) requiring cytotoxicity, able to kill both the immunizing (i.e., E418) and unrelated (e.g., K562, REX, F601, and KAS) target cells. A monoclonal antibody, anti-10H3, able to selectively inhibit the cytotoxic activity of the clones has been produced. This reagent defines a 43-kD molecule, designated TCT.1, with broad distribution in the hematopoietic system, that appears to be distinct from class I MHC gene products. A series of functional experiments using various effector/target cell combinations strongly suggested that TCT.1 may represent a unique TCR ligand involved in the interaction between these particular CTL clones and certain of the target cells tested, while others were likely to be recognized and killed through a TCR-independent natural killer-like pathway. Although further experimentation will be needed to strengthen our interpretation of the present data, this study provides additional evidence that some T lymphocytes, in particular of the gamma/delta type, may interact specifically with target cells in a non-MHC class I/II-requiring fashion. PMID- 2212944 TI - In vivo induction of anergy in peripheral V beta 8+ T cells by staphylococcal enterotoxin B. AB - We have developed a model of peripheral in vivo T cell tolerance that is induced by administration of the protein superantigen staphylococcal enterotoxin B (SEB). Rather than activating V beta 8+ T cells, in vivo administration of SEB induced in them a profound state of anergy. This was shown by their failure to proliferate to subsequent in vitro restimulation with SEB or to anti-V beta 8 antibodies. This unresponsiveness was V beta 8 specific since T cells from SEB immunized mice responded normally to other antigens. 8 d after SEB administration, there was no reduction in the number of V beta 8+ T cells or in the intensity of V beta 8 T cell receptor (TCR) expression. Although a portion of the V beta 8+ T cells from SEB-primed mice were able to express interleukin 2 receptors (IL-2Rs), they failed to proliferate in response to exogenous IL-2, indicating they were defective in their IL-2 responsiveness. 2-4 wk after SEB administration, there was a reduction of approximately 50% in the number of V beta 8+ cells in immunized compared with control animals. There was, however, no reduction in the level of TCR expression on the remaining V beta 8+ cells. These data demonstrate that proteins that activate T cells in vitro in a V beta specific manner can induce a state of anergy in peripheral T cells in vivo and may possibly further mediate clonal deletion in a portion of the tolerized cells. PMID- 2212946 TI - A cDNA clone expressed in natural killer and T cells that likely encodes a secreted protein. AB - We have isolated a series of cross-hybridizing cDNA clones, as a group designated as NKG5, from a human natural killer (NK) cell clone cDNA library. These clones show a high degree of homology with a previously described gene, 519, which was thought to be T cell specific. A comparison of the full-length cDNA sequence of NKG5 and the published sequence of 519 shows that NKG5 lacks a 242-base segment that is found in 519 and that this deletion leads to the use of a different putative translational start codon. Unlike 519, the predicted NKG5 polypeptide has an NH2-terminal sequence that is strongly hydrophobic, characteristic of a signal peptide, and lacks any additional hydrophobic regions in the remainder of the peptide, suggesting that NKG5 encodes a secreted protein. Both NKG5 and 519 are expressed in NK and T cells but not in a variety of other hematopoietic cell lines. NKG5 is an abundant transcript and its level of expression is about 40 times that of 519 in NK and T cells. Southern blot and DNA sequence analyses suggest that NKG5 and 519 mRNAs are transcripts from a single gene that has allelic polymorphism. PMID- 2212945 TI - Antibody raised against soluble CD4-rgp120 complex recognizes the CD4 moiety and blocks membrane fusion without inhibiting CD4-gp120 binding. AB - We studied the humoral response of mice immunized with soluble CD4-rgp120 complex, testing polyclonal and monoclonal antibodies (mAbs) with the aim of identifying molecular changes that take place after the first interaction between human immunodeficiency virus and the cell surface. The antisera had a paradoxically high syncytia-blocking titer associated with anti-CD4 specificity, while their capacity to inhibit CD4-gp120 binding was relatively modest. One of the mAbs produced from these responders blocks syncytia formation but does not inhibit CD4 interaction with gp120. Apparently, this mAb interacts with the CD4 moiety of CD4-gp120 complex and prevents a post-binding event necessary for membrane fusion and viral infection. PMID- 2212947 TI - Biochemical nature of an Fc mu receptor on human B-lineage cells. AB - An IgM-binding protein of approximately 60 kD has been identified on activated B cells, but not on resting and activated T cells, monocytes, or granulocytes. Here, we characterize this IgM-binding protein as a receptor for the Fc portion (CH3 and/or CH4 domains) of IgM molecules (Fc microR). The Fc microR can be expressed as a cell surface activation antigen throughout the pre-B and B cell stages in differentiation. Receptor expression is not directly linked with IgM production, as both mu- pre-B cells and isotype-switched B cells may express the Fc microR. The receptor molecules produced by both pre-B and B cells are identical in size and are characterized as an acidic sialoglycoprotein with O linked, but no N-linked, oligosaccharide. The Fc microR is anchored to the surface of B-lineage cells via a glycosyl phosphatidylinositol linkage. The Fc microR is thus the third member of a family of Fc receptors expressed on B lineage cells, and its preferential expression on activated B cells suggests a potential role in the response to antigens. PMID- 2212949 TI - Complement component C3 fixes selectively to the major outer membrane protein (MOMP) of Legionella pneumophila and mediates phagocytosis of liposome-MOMP complexes by human monocytes. AB - Legionella pneumophila is a facultative intracellular bacterial pathogen that parasitizes human monocytes and alveolar macrophages. Previous studies from this laboratory have shown that monocyte complement receptors CR1 and CR3 and complement component C3 in serum mediate L. pneumophila phagocytosis. In this study, we have explored C3 fixation to L. pneumophila. We developed a whole-cell enzyme-linked immunosorbent assay (ELISA) to measure C3 fixation to the bacterial surface. By this assay, C3 fixes to L. pneumophila that are opsonized in fresh nonimmune serum, and C3 fixation takes place via the alternative pathway of complement activation. Immunoblot analysis of opsonized L. pneumophila indicated that C3 fixes selectively to specific acceptor molecules of L. pneumophila. Consistent with this, when nitrocellulose blots of whole L. pneumophila or bacterial components are incubated in fresh nonimmune serum, C3 fixes exclusively to the major outer membrane protein (MOMP) of L. pneumophila, a porin; C3 does not fix to L. pneumophila LPS on these blots. To further explore the role of MOMP in C3 fixation and phagocytosis, we reconstituted purified MOMP into liposomes. By the ELISA, MOMP-liposomes, but not plain liposomes lacking MOMP, avidly fix C3. Consistent with a dominant role for MOMP in C3 fixation, MOMP-liposomes form a C3 complex of the same apparent molecular weight as whole L. pneumophila in nonimmune serum. Opsonized radioiodinated MOMP-liposomes avidly adhere to monocytes, and adherence is dose dependent upon serum. By electron microscopy, opsonized MOMP-liposomes are efficiently phagocytized by human monocytes, and phagocytosis takes place by a conventional appearing form of phagocytosis. This study demonstrates that C3 fixes selectively to the MOMP of L. pneumophila, and that, in the presence of nonimmune serum, MOMP can mediate phagocytosis of liposomes and, potentially, phagocytosis of intact L. pneumophila by human monocytes. PMID- 2212948 TI - An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis. AB - Uncertainty regarding pathogenic mechanisms has been a major impediment to effective prevention and treatment for human neurologic diseases such as multiple sclerosis, tropical spastic paraparesis, and AIDS demyelinating disease. Here, we implicate lymphotoxin (LT) (tumor necrosis factor beta [TNF-beta]) and TNF-alpha in experimental allergic encephalomyelitis (EAE), a murine model of an autoimmune demyelinating disease. In this communication, we report that treatment of recipient mice with an antibody that neutralizes LT and TNF-alpha prevents transfer of clone-mediated EAE. LNC-8, a myelin basic protein-specific T cell line, produces high levels of LT and TNF-alpha after activation by concanavalin A, antibody to the CD-3 epsilon component of the T cell receptor, or myelin basic protein presented in the context of syngeneic spleen cells. LNC-8 cells transfer clinical signs of EAE. When LNC-8 recipient mice were also treated with TN3.19.12, a monoclonal antibody that neutralizes LT and TNF-alpha, the severity of the transferred EAE was reduced, while control antibodies did not alter the disease. The effect of anti-LT/TNF-alpha treatment was long lived and has been sustained for 5 mo. These findings suggest that LT and TNF-alpha and the T cells that produce them play an important role in EAE. PMID- 2212950 TI - Activation of protein kinase C results in the displacement of its myristoylated, alanine-rich substrate from punctate structures in macrophage filopodia. AB - The myristoylated, alanine-rich C kinase substrate (MARCKS) is a prominent substrate for protein kinase C (PKC) in a variety of cells, and has been implicated in diverse cellular processes including neurosecretion, fibroblast mitogenesis, and macrophage activation. In macrophages that have spread on the substratum, MARCKS has a punctate distribution at the cell-substratum interface of pseudopodia and filopodia. At these points, MARCKS co-localizes with vinculin and talin. Activation of PKC with phorbol esters results in the rapid disappearance of punctate staining of MARCKS, but not vinculin or talin, and is accompanied by cell spreading and loss of filopodia. The morphological changes and disappearance of punctate staining follow a time-course that closely approximates both the PKC-dependent phosphorylation of MARCKS, and its phosphorylation-dependent release from the plasma membrane. Our results suggest a role for PKC-dependent phosphorylation of MARCKS in the regulation of the membrane cytoskeleton. PMID- 2212951 TI - Interleukin 2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity. AB - To study the effects of localized secretion of cytokines on tumor progression, the gene for human interleukin 2 (IL-2) was introduced via retroviral vectors into CMS-5 cells, a weakly immunogenic mouse fibrosarcoma cell line of BALB/c origin. Secretion of low levels of IL-2 from the tumor cells abrogated their tumorigenicity and induced a long-lasting protective immune response against a challenge with a tumorigenic dose of parental CMS-5 cells. Co-injection of IL-2 producing CMS-5 cells with unmodified tumor cells inhibited tumor formation even when highly tumorigenic doses of CMS-5 cells were used. Cytolytic activity in mice injected with parental CMS-5 cells was transient and was greatly diminished 3 wk after injection, as commonly observed in tumor-bearing animals. However, in mice injected with IL-2-producing cells, tumor-specific cytolytic activity persisted at high levels for the duration of the observation period (at least 75 d). High levels of tumor-specific cytolytic activity could also be detected in parental CMS-5 tumor-bearing animals 18 d after inoculation with tumor cells, if IL-2-producing CMS-5 cells but not unmodified parental tumor cells were used as targets. These studies highlight the potential advantages of localized secretion of cytokines mediated via gene transfer to induce potent anti-tumor immune responses. PMID- 2212952 TI - Expression of HLA-B27 in transgenic mice is dependent on the mouse H-2D genes. AB - HLA-B27 transgenic mice in the context of various H-2 haplotypes were produced. A high expression of the HLA-B27 antigen was observed in mice homozygous for H-2b, H-2f, H-2s, H-2p, H-2r, and H-2k haplotypes. Mice of the H-2v haplotype expressed HLA-B27 at an intermediate level. Expression of HLA-B27 was minimal in mice of the H-2q and H-2d haplotypes. This was observed both on the B10 background and in DBA/2 or BALB/c mice. Only minimal expression of HLA-B27 could be detected in B10.PL (KuDd) or B10.RKDB (KkSkDdLb) mice, indicating that the low level of HLA B27 expression maps to the H-2D gene or a very closely linked gene. Integration and transcription of the HLA-B27 gene does not appear to be different between high-expressing haplotypes and low-expressing haplotypes as determined by Southern and Northern blot analysis. However, expression of HLA-B27 on the cell surface correlated with the amount of HLA-B27 and beta 2M that could be immunoprecipitated with an anti-B27 antibody. Therefore, the association of the B27 heavy chain with endogenous beta 2M and subsequent expression on the cell surface are disrupted in mice with some class I H-2D genes. Possible mechanisms that might contribute to this defect in assembly, transport, and expression of class I molecules are discussed. PMID- 2212953 TI - Analysis of T cell signaling by class I MHC molecules: the cytoplasmic domain is not required for signal transduction. AB - The structural requirements for signal transduction by class I major histocompatibility complex (MHC) molecules were examined. Native or mutant HLA-A2 or HLA-B27 constructs lacking most of their cytoplasmic domains were co transfected with pSV2neo into Jurkat cells. Transfection of either native or mutant constructs resulted in a comparable expression of the gene products. Stimulation of transfectants expressing either native or truncated A2 or B27 molecules with specific mAb evoked an increase in [Ca2+]i upon crosslinking. Moreover, crosslinking native or truncated A2 or B27 induced IL-2 production upon co-stimulation with phorbol myristate acetate. These results confirm that crosslinking class I MHC molecules transduces an activation signal to human T cells. Effective signaling was observed when all but four of the intracytoplasmic residues were deleted, indicating that signal transduction does not require this portion of the molecule. PMID- 2212955 TI - Cholecystokinin and glucose-induced insulinaemia in dogs with and without pancreatic acinar atrophy. AB - The entero-insular hormonal axis was studied in eleven conscious Beagle dogs, loaded with glucose orally and intravenously. In five of them, exocrine pancreatic atrophy was induced by pancreatic duct occlusion with prolamine, and documented by means of the p-amino-benzoic acid test. After oral glucose, the duct-occluded dogs displayed higher blood glucose (log area 4.12 +/- 0.07 versus 3.76 +/- 0.10; p less than 0.01), less plasma insulin (log area 3.56 +/- 0.08 versus 3.99 +/- 0.08; p less than 0.01) and less cholecystokinin-like immunoreactivity (log area 2.64 +/- 0.09 versus 3.10 +/- 0.14; p less than 0.01) than controls. In controls, the peripheral venous insulin concentrations were higher after oral than after isoglycaemic intravenous glucose, and this difference was no longer demonstrable in duct-occluded dogs. In the latter, gel permeation chromatography of pool plasma after oral glucose revealed a relative decrease of cholecystokinin-like immunoreactivity species, which eluted at the positions of sulphated cholecystokinin octapeptide, cholecystokinin-33 and cholecystokinin-39, and at a position intermediate between these two. Also in the duct-occluded animals, intravenous infusion of sulphated cholecystokinin octapeptide, in addition to oral glucose, resulted in an increase in plasma insulin (log area 3.83 +/- 0.10 versus 3.64 +/- 0.06; p less than 0.01) and an improvement in oral glucose tolerance. It is concluded that in the dog 1) the absence of pancreatic acinar tissue is associated with a loss of gastrointestinal factors mediating glucose-induced insulin secretion, and 2) reduction of circulating endogenous cholecystokinin species may account at least in part for this defect. PMID- 2212954 TI - Activation of platelets by eosinophil granule proteins. AB - Two of the four principal cationic proteins of the eosinophil granule, major basic protein (MBP) and eosinophil peroxidase (EPO), were shown to be platelet agonists. Both MBP and EPO evoked a dose-dependent nonlytic secretion of platelet 5-hydroxytryptamine in unstirred platelet suspensions even in the presence of 10 microM indomethacin. MBP also evoked secretion of platelet alpha granule and lysosome components. Secretion by MBP and EPO was inhibited by 1 microM PGE1, but the nature of the inhibition differed from that observed with thrombin. Thus, MBP and EPO can be classified as strong platelet agonists with a distinct mechanism of activation. PMID- 2212956 TI - The use of cluster analysis in clinical chemical diagnosis of liver diseases. AB - Diagnostic judgement is usually based on recognition of patterns. Unfortunately more than three quantitative data cannot be judged simultaneously without help of mathematical methods. Working on laboratory reports, a clinician usually goes linearly through the columns and reduces quantitative to qualitative data. Therefore the medical decision process should be improved if data reduction is performed with the aid of mathematical methods for pattern recognition. A total of 191 consecutive outpatients with a tentative or proven diagnosis of hepatobiliary disease were examined clinically, clinically chemically and partly histologically. Nineteen clinical chemical parameters were determined. Prior to pattern cognition, a principal component analysis was performed. Using six factors, accounting for 72.4% of total variance, cluster analysis was done, applying a hierarchical algorithm for ascertaining a starting partition, followed by the k-means algorithm. The validity of the solution was scrutinized, and a stable structure was found with nine clusters. Patients with a rejected suspect of liver disease were mainly located in clusters 1, 6 and 7. Cluster 1 also contains patients with compensated cirrhosis without inflammation, idiopathic hyperbilirubinaemia, focal nodular hyperplasia and haemangioma of the liver. In contrast, one third of cirrhoses, all with inflammatory activity were assigned to cluster 5. Patients with primary biliary disease were distributed among clusters 2, 3 and 4. All malignant neoplasias were assigned to cluster 9. More than 50% of fatty livers were classified to cluster 7. Cluster 2 and 8 contain only one patient with primary biliary cirrhosis (cluster 2) and fatty liver hepatitis (cluster 8). The follow-up of 66 patients also showed clinically meaningful changes of cluster assignment. PMID- 2212958 TI - The clinical evaluation of cobalamin deficiency by determination of methylmalonic acid in serum or urine is not invalidated by the presence of heterozygous methylmalonic-acidaemia. AB - It is well established that accumulation of methylmalonic acid may provide an early clue to the existence of tissue cobalamin (vitamin B12) deficiency. To verify whether methylmalonic acid accumulates in adult heterozygotes for inherited methylmalonic-acidaemia and thereby gives "false" positive test results for cobalamin deficiency, we measured the concentration of methylmalonic acid in serum and its urinary excretion in six patients of three children with severe methylmalonic-acidaemia. We found levels of methylmalonic acid similar to those in normal subjects. In serum, the concentrations of methylmalonic acid ranged from 0.12 to 0.39 mumol/l (reference range: 0.05-0.44 mumol/l). In urine, the values ranged from 1.18 to 2.48 mmol per mol of creatinine (reference range: 0.58 3.56). We conclude that the 2% of carriers of inherited methylmalonic-acidaemia in the general population do not invalidate the usefulness of measurement of methylmalonic acid in serum or urine for the clinical evaluation of cobalamin deficiency. PMID- 2212959 TI - Kits for the diagnosis of infectious mononucleosis compared with the Paul-Bunnell test. AB - We compared the results obtained with six different test kits for infectious mononucleosis with those obtained with the Paul-Bunnell test. The investigation was carried out in one laboratory using 149 selected pools of patient sera. Each pool was tested three times with the Paul-Bunnell test and once with each kit. The results obtained with the kits were grouped according to the titre found with the Paul-Bunnell test. The percentage of positive results within each group was calculated for each kit. The Paul-Bunnell titre, which would have classified 50% of the specimens as positive, was estimated for each kit and this was designated the 50% cut off value. In general, there was good agreement. However, false positive test results were found rather frequently with one kit (19%) and the 50% cut off values differed. One kit showed a 50% cut off value at about 8, another at about 16, and the rest at between 16 and 32. We suggest the introduction of improved internal quality control combined with external quality assessment. PMID- 2212957 TI - HLA class I-, complement C4- and 21-hydroxylase probes in the genetic analysis of 21-hydroxylase deficiency. AB - In order to develop an optimal strategy for the prenatal diagnosis of steroid 21 hydroxylase (EC 1.14.99.10) deficiency, we investigated 16 affected families with salt wasting syndrome. Genomic DNA derived from peripheral white blood cells was digested with 6 different restriction enzymes. Hybridisation was carried out with DNA-probes of the HLA class I region, the 21-hydroxylase- and the complement C4 genes. All the families were informative in at least three different loci. Twelve out of the 16 families were informative by neutral polymorphisms or disease related variants of the 21-hydroxylase gene or the adjoining C4 locus. The reliability of prediction in these cases exceeded 99%. The remaining 4 families were informative only in the HLA class I region, tantamount to a reliability of prediction of about 98%. In none of the cases did we have to fall back on semiquantitative gene dose assessments. We further describe new polymorphisms in the 21-hydroxylase region for the enzyme Pvu II and EcoR V. PMID- 2212960 TI - Evaluation of a new enzyme immunoassay system for free thyroxine (Enzymun-Test FT4). AB - Free thyroxine (FT4) represents the metabolically active fraction of the circulating thyroid hormone thyroxine (T4). In this paper the results of the evaluation of a newly developed FT4 assay are reported. This assay system is based on an enzyme-labelled one-step immunoassay. The within-run imprecision, checked using serum pools and several commercial reference materials, showed a coefficient of variation (CV) of between 0.8 and 9.8%, depending on the reference material used. The between-run imprecision showed a CV of between 1.0 and 13.2%. Accuracy experiments yielded values between 80 and 116%. When the new FT4 was compared with the calculation of an index for free thyroxine (FT4I; derived from either the ratio of T4/thyroxine binding coefficient of from T4/thyroxine binding globulin) in a number of samples in the hypo-, eu- and hyperthyroid range, a good correlation was obtained. The same was true when the new FT4 assay was compared with a widely used two-step radioimmunoassay (y = -0.146 + 0.943 x). In euthyroid subjects the measured FT4 concentration was 10.3-25.8 pmol/l. No effect was evident when the influence of EDTA and citrate was investigated, whereas addition of heparin led to an increase in FT4 concentration of about 12 to 15%. Investigation of the possible influence of a large number of drugs showed that probenezid, carbamazepine and furosemide led to an increase in the measured FT4 concentration. Dialysis increased the FT4 concentration, as measured in patients before and after haemodialysis. No effect of alteration in protein concentration and/or protein distribution of FT4 concentration could be detected. In pregnancy, FT4 values were within the normal range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2212961 TI - European Multicentre Evaluation of the ESAT 6660. AB - The analytical performance of the glucose analyser ESAT 6660 from Eppendorf was studied according to the ECCLS guidelines and partly according the SFBC protocol in a multicentre evaluation involving laboratories from three European countries. The glucose determination in serum and in haemolysate was studied. The following results were obtained. 1. The precision was as good as or better than the precision of the comparison instruments. The coefficients of variation were between 1.1 and 3.4% for the between-days imprecision and between 0.35 and 1.45% for the within-run imprecision experiment. 2. The recovery of control sera values compared with the hexokinase method was between 94.3 and 102.6%. 3. With patient specimens as good agreement was found between the results obtained with the ESAT 6660 and the different comparison instruments (ASTRA, Hitachi 737 and ACP 5040). 4. A drift effect of 1.1-2.3% occurred in 5 of 21 experiments, depending on the individual enzyme membrane. 5. Sample carry-over was not observed. 6. A linearity between 0.5 and 50 mmol/l was found, exceeding the manufacturer's claims. 7. Several different endogenous and exogenous interferences were investigated. No interfering effect was detected for endogenous substances. A positive interference was observed by ascorbic acid at a concentration above 350 mg/l. 8. The practicability of the instrument was judged as very good. It was considered as a disadvantage that the instrument is not capable of piercing sample lids. Also the numeration of samples is not very convenient. PMID- 2212962 TI - Genital chlamydia infection. PMID- 2212963 TI - Child sexual abuse and the skin. PMID- 2212964 TI - Headache and depression. PMID- 2212965 TI - Headache: a marker of depression. AB - Patients who presented with a chief complaint of headache in the outpatient family practice setting were found to have a high prevalence of depression (63%) by the Zung Self-Rating Depression Scale (SDS) index. A statistically significant relationship was found between the frequency of headaches (P = .03) with level of depression. In fact, 74% of patients with headaches recurring almost every day had a clinically significant depression diagnosed as defined by the Zung SDS score. The Zung SDS score also correlated with the length of time that the problem of headache existed (P less than .05). Item analysis of the individual 20 item depression score revealed that four questions accounted for 93% of the variance. This analysis suggests that shorter, more abbreviated screening questions could be developed and refined in the future for use by the busy clinician. Headache is an important marker for depression in the primary care setting. It can be inferred from this study that the clinician may need to focus more on treating the entity of depression than on treating just the symptom of headache. PMID- 2212967 TI - Smoking in adolescence: methods for health education and smoking cessation. A MIRNET study. AB - The purpose of this study was to explore smoking behaviors and attitudes among adolescents. A self-administered questionnaire was used to sample adolescents presenting for health care to physicians belonging to MIRNET, a network of family physicians collaborating on research across Michigan. The questionnaire was anonymous and was completed before the visit. Physicians or office nurses were asked to complete a brief face sheet on their patient's demographic information and smoking status, which was linked to the questionnaire through a code number. Twenty-seven percent of female patients and 16% of male patients were smoking and 57% had tried smoking. Knowledge regarding health risks of smoking was high, and the major reasons given for starting to smoke were curiosity and peer behavior. Current smokers reported greater alcohol and marijuana use and cited problems with stress and anxiety, peer behavior, boredom, and the influence of smoking parents and relatives as factors in continuing to smoke. Patients' suggestions for successful smoking cessation focused on peers, explicit messages through pictures, and medication. PMID- 2212966 TI - Community screening for hypercholesterolemia. AB - This study focused on a cholesterol screening and education program conducted in Scottsdale, Arizona, to determine the prevalence of hypercholesterolemia among the volunteer participants, and whether such a program motivates lifestyle changes and physician follow-up. The study also examined whether participants used the program to monitor known hypercholesterolemia. During the 6-month program, 1228 individuals were screened. Of these, 29% had a previous history of elevated cholesterol and 5% were on cholesterol-lowering medication. Of the group with no previous history of hypercholesterolemia, 41% had cholesterol levels higher than 5.17 mmol/L (200 mg/dL) and 10% had levels higher than 6.21 mmol/L (240 mg/dL). A subgroup of 120 persons with levels higher than 6.21 mmol/L (240 mg/dL) were contacted 4 to 6 months after the screening. Most of this group reported improvement in diet and exercise patterns, and 58% had consulted a physician. These results suggest that people with known hypercholesterolemia are using community screening programs to monitor their own cholesterol levels, and that such programs identity new high-risk individuals. Program participants appear to change diet and exercise patterns and to seek physician follow-up. PMID- 2212968 TI - Oscillometric finger blood pressure versus brachial auscultative blood pressure recording. AB - In this study, a recently marketed proprietary finger blood pressure monitor, the Marshall, Astro F-88, was compared with the standard auscultative brachial mercury sphygmomanometer on 125 subjects. Measurements were undertaken according to the standards set by the American Heart Association. Sensitivity of the finger blood pressure measurement was 76% for systolic and 75% for diastolic blood pressure in diagnosis of high blood pressure (systolic greater than 140 mm Hg and diastolic greater than 90 mm Hg). Specificity was 86% for systolic and 82% for diastolic blood pressure. Positive predictive values were 58% for systolic and 38% for diastolic blood pressure in the study population in which prevalence of hypertension was 12%. The correlation coefficient (Pearson) for systolic values between devices was 0.76 (P less than .0001) and 0.57 (P less than .0001) for diastolic pressure. Values obtained by the finger monitor were found to be higher than those obtained by the mercury sphygmomanometer. Mean differences and standard deviations (paired t test) for systolic and diastolic pressures between the two devices were 2.3 +/- 14.9 mm Hg (P less than .08) and 2.9 +/- 14.5 mm Hg (P less than .02), respectively. These values are not in accordance with the proposed national standards because only 48% of the systolic and 37% of the diastolic blood pressure measurements were within 5 mm Hg of the mercury sphygmomanometer measurements. Therefore, although these differences may well be due to different techniques of monitoring employed by the devices, this device is not recommended for evaluation of blood pressure. PMID- 2212969 TI - Physicians' role in managing emotionally distressed patients already in psychotherapy. AB - Much has been written on how physicians should manage patients in emotional distress, including recommendations for making successful referrals to mental health providers. Little has been written, however, on the management of distressed patients who are already in psychotherapy. This article, drawing on three cases, a review of the literature, and systems theory, presents recommendations for managing these patients. Physicians are encouraged to assess these patients for risk of suicide or homicide, substance abuse, and indications for psychotropic medication. They are advised to seek a patient's permission to speak to his or her therapist when the patient may be in immediate danger, when psychotropic medications, hospitalization, or psychiatric consultation is considered, and when the patient fails to respond to ongoing treatment. For patients whose therapists are not psychiatrists, psychiatric consultation is recommended when there are questions about psychotropic medications, when psychiatric and substance abuse disorders coexist, and when hospitalization is considered. Therapists skilled in applying systems theory should be consulted when the patient, psychotherapist, and physician agree that the patient is not making sufficient progress. In most cases, however, physicians should reassure patients about distressing symptoms, avoid expressing opinions about the therapist and psychosocial issues, and encourage patients to renew or to expand their commitment to their psychotherapy. PMID- 2212970 TI - Comprehensive geriatric assessment recommendations: adherence of family practice residents. AB - A study was performed to determine whether family practice residents followed recommendations made by a comprehensive geriatric assessment clinic. Of 109 consecutive consultations, 27 patients had follow-up visits with family practice residents who participated in the assessment and who subsequently served as their primary care physicians. Adherence of residents to 437 clinic recommendations was monitored for 90 days by medical record review. Although recommendations to begin or increase a medication were followed 85.4% of the time, residents followed recommendations to stop or decrease medications less than 65% of the time. Recommendations to order a specific laboratory test or x-ray examination were acted on 70.3% of the time. Preventive recommendations were followed only 54.3% of the time. Residents' adherence to team-based care plans varied widely by type of recommendation. Special efforts are needed to increase compliance with comprehensive geriatric assessment clinic recommendations, particularly those for preventive services. PMID- 2212971 TI - Should a major imaging procedure (CT or MRI) be required in the workup of dementia? An affirmative view. PMID- 2212972 TI - Should a major imaging procedure (CT or MRI) be required in the workup of dementia? An opposing view. PMID- 2212973 TI - Long-term outcomes of primary care residency choice by graduating medical students in one medical school. AB - The ratio of primary care physicians to subspecialists is of major importance to the future of American medicine. This study examined the output of primary care physicians by a state-supported medical school that has a goal of placing 50% of its graduates in primary care. Data were obtained from alumni office questionnaires and published board-certification listings for 1102 graduates of the University of Kentucky College of Medicine from 1973 through 1983. Fifty percent of these graduates chose residency training in primary care. Of all 1102 graduates, 37% are categorized as practicing primary care physicians; 29% of the total are board certified in a primary care discipline. Attrition from primary care as an initial career choice at entry into residency was 26%. With declining medical student interest in primary care and a shortage of primary care physicians, new initiatives in medical education and in the practice of medicine are necessary to balance the specialty distribution of physicians more favorably toward primary care. PMID- 2212974 TI - Brown spider bites. PMID- 2212975 TI - Spontaneous pneumomediastinum: evaluation and treatment. PMID- 2212976 TI - Assessment of a patient-held minirecord for adult health maintenance. PMID- 2212977 TI - Intrinsic gating of inward rectifier in bovine pulmonary artery endothelial cells in the presence or absence of internal Mg2+. AB - Inward rectifier (IR) currents were studied in bovine pulmonary artery endothelial cells in the whole-cell configuration of the patch-clamp technique with extracellular K+ concentrations, [K+]o, ranging from 4.5 to 160 mM. Whether the concentration of free Mg2+ in the intracellular solution, [Mg2+]i, was 1.9 mM or nominally 0, the IR exhibited voltage- and time-dependent gating. The IR conductance was activated by hyperpolarization and deactivated by depolarization. Small steady-state outward IR currents were present up to approximately 40 mV more positive than the K+ reversal potential, EK, regardless of [Mg2+]i. Modeled as a first-order C in equilibrium O gating process, both the opening rate, alpha, and the closing rate, beta, were exponentially dependent on voltage, with beta more steeply voltage dependent, changing e-fold for 9 mV compared with 18 mV for an e-fold change in alpha. Over all [K+]o studied, the voltage dependence of alpha and beta shifted along with EK, as is characteristic of IR channels in other cells. The steady-state voltage dependence of the gating process was well described by a Boltzmann function. The half-activation potential was on average approximately 7 mV negative to the observed reversal potential in all [K+]o regardless of [Mg2+]i. The activation curve was somewhat steeper when Mg-free pipette solutions were used (slope factor, 4.3 mV) than when pipettes contained 1.9 mM Mg2+ (5.2 mV). The simplest interpretation of these data is that IR channels in bovine pulmonary artery endothelial cells have an intrinsic gating mechanism that is not due to Mg block. PMID- 2212978 TI - Gating of single non-Shaker A-type potassium channels in larval Drosophila neurons. AB - The voltage-dependent gating of transient A2-type potassium channels from primary cultures of larval Drosophila central nervous system neurons was studied using whole-cell and single-channel voltage clamp. A2 channels are genetically distinct from the Shaker A1 channels observed in Drosophila muscle, and differ in single channel conductance, voltage dependence, and gating kinetics. Single A2 channels were recorded and analyzed at -30, -10, +10, and +30 mV. The channels opened in bursts in response to depolarizing steps, with three to four openings per burst and two to three bursts per 480-ms pulse (2.8-ms burst criterion). Mean open durations were in a range of 2-4 ms and mean burst durations in a range of 9-17 ms. With the exception of the first latency distributions, none of the means of the distributions measured showed a consistent trend with voltage. Macroscopic inactivation of both whole-cell A currents and ensemble average currents of single A2 channels was well fitted by a sum of two exponentials. The fast time constants in different cells were in a range of 9-25 ms, and the slow time constants in a range of 60-140 ms. A six-state kinetic model (three closed, one open, two inactivated states) was tested at four command voltages by fitting frequency histograms of open durations, burst durations, burst closed durations, number of openings per burst, and number of bursts per trace. The model provided good fits to these data, as well as to the ensemble averages. With the exception of the rates leading to initial opening, the transitions in the model were largely independent of voltage. PMID- 2212980 TI - Ultraslow contractile inactivation in frog skeletal muscle fibers. AB - After a contracture response, skeletal muscle fibers enter into a state of contractile refractoriness or inactivation. Contractile inactivation starts soon after membrane depolarization, and causes spontaneous relaxation from the contracture response. Here we demonstrate that contractile inactivation continues to develop for tens of seconds if the membrane remains in a depolarized state. We have studied this phenomenon using short (1.5 mm) frog muscle fibers dissected from the Lumbricalis brevis muscles of the frog, with a two-microelectrode voltage-clamp technique. After a contracture caused by membrane depolarization to 0 mV, from a holding potential of -100 mV, a second contracture can be developed only if the membrane is repolarized beyond a determined potential value for a certain period of time. We have used a repriming protocol of 1 or 2 s at -100 mV. After this repriming period a fiber, if depolarized again to 0 mV, may develop a second contracture, whose magnitude and time course will depend on the duration of the period during which the fiber was maintained at 0 mV before the repriming process. With this procedure it is possible to demonstrate that the inactivation process builds up with a very slow time course, with a half time of approximately 35 s and completion in greater than 100 s. After prolonged depolarizations (greater than 100 s), the repriming time course is slower and the inactivation curve (obtained by plotting the extent of repriming against the repriming membrane potential) is shifted toward more negative potentials by greater than 30 mV when compared with similar curves obtained after shorter depolarizing periods (10-30 s). These results indicate that important changes occur in the physical state of the molecular moiety that is responsible for the inactivation phenomenon. The shift of the inactivation curve can be partially reversed by a low concentration (50 microM) of lanthanum ions. In the presence of 0.5 mM caffeine, larger responses can be obtained even after prolonged depolarization periods, indicating that the fibers maintain their capacity to liberate calcium. PMID- 2212979 TI - Anion-coupled Na efflux mediated by the human red blood cell Na/K pump. AB - The red cell Na/K pump is known to continue to extrude Na when both Na and K are removed from the external medium. Because this ouabain-sensitive flux occurs in the absence of an exchangeable cation, it is referred to as uncoupled Na efflux. This flux is also known to be inhibited by 5 mM Nao but to a lesser extent than that inhibitable by ouabain. Uncoupled Na efflux via the Na/K pump therefore can be divided into a Nao-sensitive and Nao-insensitive component. We used DIDS treated, SO4-equilibrated human red blood cells suspended in HEPES-buffered (pHo 7.4) MgSO4 or (Tris)2SO4, in which we measured 22Na efflux, 35SO4 efflux, and changes in the membrane potential with the fluorescent dye, diS-C3 (5). A principal finding is that uncoupled Na efflux occurs electroneurally, in contrast to the pump's normal electrogenic operation when exchanging Nai for Ko. This electroneutral uncoupled efflux of Na was found to be balanced by an efflux of cellular anions. (We were unable to detect any ouabain-sensitive uptake of protons, measured in an unbuffered medium at pH 7.4 with a Radiometer pH-STAT.) The Nao-sensitive efflux of Nai was found to be 1.95 +/- 0.10 times the Nao sensitive efflux of (SO4)i, indicating that the stoichiometry of this cotransport is two Na+ per SO4=, accounting for 60-80% of the electroneutral Na efflux. The remainder portion, that is, the ouabain-sensitive Nao-insensitive component, has been identified as PO4-coupled Na transport and is the subject of a separate paper. That uncoupled Na efflux occurs as a cotransport with anions is supported by the result, obtained with resealed ghosts, that when internal and external SO4 was substituted by the impermeant anion, tartrate i,o, the efflux of Na was inhibited 60-80%. This inhibition could be relieved by the inclusion, before DIDS treatment, of 5 mM Cli,o. Addition of 10 mM Ko to tartrate i,o ghosts, with or without Cli,o, resulted in full activation of Na/K exchange and the pump's electrogenicity. Although it can be concluded that Na efflux in the uncoupled mode occurs by means of a cotransport with cellular anions, the molecular basis for this change in the internal charge structure of the pump and its change in ion selectivity is at present unknown. PMID- 2212981 TI - The increase of oxygen consumption after a flash of light is tightly coupled to sodium pumping in the lateral ocellus of barnacle. AB - In the lateral ocellus of the barnacle, we have tested the hypothesis that the transient increase of oxygen consumption (delta QO2) induced by light results from an increase in the rate of Na+ pumping. With a Na(+)-sensitive microelectrode, we measured the intracellular concentration of Na+ (Nai) in the photoreceptor cells. Nai was 17.6 +/- 1.2 mM (SE; n = 18) in darkness and it increased transiently by 10-20 mM after an 80-ms flash of intense light. The increase of Nai recovered in about the same time as the delta QO2, and the Na+/O2 ratio was 19.2 +/- 3.8 (SE; n = 6). Removing Na+ from the bath caused the delta QO2 to decrease by 79 +/- 3% (SE; n = 5). Exposure to 25 microM ouabain inhibited Na+ pumping and abolished the delta QO2. Removal of K+ from the bathing solution inhibited Na+ pumping in darkness, but mostly shortened the duration of the delta QO2; with a K(+)-sensitive microelectrode, we measured pericellular [K+] and found that it increased after the flash for about the same time as the delta QO2. Increasing Na+ pumping in darkness by reintroducing K+ in the bath or by injecting Na+ into one of the photoreceptor cells induced a delta QO2. Finally, intracellular injection of adenosine diphosphate and inorganic phosphate (ADP + Pi), the metabolic products of ATP splitting by the Na+ pump, also induced a delta QO2 in darkness. We conclude that all the results obtained are consistent with the formulated hypothesis. PMID- 2212982 TI - Membrane capacitance in frog cut twitch fibers mounted in a double vaseline-gap chamber. AB - In experiments on cut muscle fibers mounted in a double Vaseline-gap chamber, electrical measurements are usually made by measuring the voltage V1(t) in one end pool and by passing current I2(t) from the other end pool to the central pool, which is usually clamped to earth potential. The voltage in the current passing end pool is denoted by V2(t). This article describes how the value of the holding current, Ih, and the values of delta V2(infinity)/delta V1(infinity) and delta I2(infinity)/delta V1(infinity) that are associated with a small change in V1(t) can be used to estimate the linear cable parameters rm, ri, and re in a cut fiber that has been equilibrated with a Cs-containing internal solution. rm, ri, and re represent, respectively, the resistance of the plasma membranes, the internal longitudinal resistance, and the external longitudinal resistance under the Vaseline seals, all for a unit length of fiber. The apparent capacitance, Capp, of the preparation is defined to equal integral of infinity 0 delta I2,tr(t) dt/delta V1(infinity), in which delta I2,tr(t) represents the transient component of current that is associated with a change in V1(t) of amplitude delta V1(infinity). A method is described to estimate cm, the capacitance of the plasma membranes per unit length of fiber, from Capp and the values of rm, ri, and re. In experiments carried out with a tetraethylammonium chloride (TEA.Cl) solution at 13-14 degrees C in the central pool, cm remained stable for as long as 3-4 h. The values of cm, 0.19 microF/cm on average, and their variation with fiber diameter are similar to published results from intact fibers. This article also describes the different pathways that are taken by the current that flows from the current-passing end pool to the central pool. Approximately two-thirds of delta I2,tr(t) flows across the capacitance of the plasma membranes in the central-pool region. The rest flows either across plasma membranes that are under the two Vaseline seals or directly from the current-passing end pool to the central pool, across the external longitudinal resistance under the Vaseline seal. [There is also a current that flows directly from the voltage-measuring end pool to the central pool but this does not contribute to delta I2,tr(t).] PMID- 2212983 TI - Intramembranous charge movement in frog cut twitch fibers mounted in a double vaseline-gap chamber. AB - Intramembranous charge movement was measured in cut twitch fibers mounted in a double Vaseline-gap chamber with either a tetraethylammonium chloride (TEA.Cl) or a TEA2.SO4 solution (13-14 degrees C) in the central pool. Charge vs. voltage data were fitted by a single two-state Boltzmann distribution function. The average values of V (the voltage at which steady-state charge is equally distributed between the two Boltzmann states), k (the voltage dependence factor), and qmax/cm (the maximum charge divided by the linear capacitance, both per unit length of fiber) were V = -53.3 mV (SEM, 1.1 mV), k = 6.3 mV (SEM, 0.3 mV), qmax/cm = 18.0 nC/microF (SEM, 1.1 nC/microF) in the TEA.Cl solution; and V = 35.1 mV (SEM, 1.8 mV), k = 10.5 mV (SEM, 0.9 mV), qmax/cm = 36.3 nC/microF (SEM, 3.2 nC/microF) in the TEA2.SO4 solution. These values of k are smaller than those previously reported for cut twitch fibers and are as small as those reported for intact fibers. If a correction is made for the contributions of currents from under the Vaseline seals, V = -51.2 mV (SEM, 1.1 mV), k = 7.2 mV (SEM, 0.4 mV), qmax/cm = 22.9 nC/microF (SEM, 1.4 nC/microF) in the TEA.Cl solution; and V = 34.0 mV (SEM, 1.9 mV), k = 10.1 mV (SEM, 1.1 mV), qmax/cm = 38.8 nC/microF (SEM, 3.2 nC/microF) in the TEA2.SO4 solution. With this correction, however, the fit of the theoretical curve to the data is poor. A good fit with this correction can be obtained with a sum of two Boltzmann distribution functions. The first has average values V = -33.0 mV (SEM, 2.8 mV), k = 11.0 mV (SEM, 0.5 mV), qmax/cm = 10.6 nC/microF (SEM, 1.0 nC/microF) in the TEA.Cl solution; and V = -20.0 mV (SEM, 3.3 mV), k = 17.0 mV (SEM, 2.0 mV), qmax/cm = 36.4 nC/microF (SEM, 2.3 nC/microF) in the TEA2.SO4 solution. The second has average values V = -56.5 mV (SEM, 1.3 mV), k = 2.9 mV (SEM, 0.4 mV), qmax/cm = 13.2 nC/microF (SEM, 1.0 nC/microF) in the TEA.Cl solution; and V = -41.6 mV (SEM, 1.4 mV), k = 2.5 mV (SEM, 0.8 mV), qmax/cm = 11.8 nC/microF (SEM, 1.7 nC/microF) in the TEA2.SO4 solution. When a fiber is depolarized to near V of the second Boltzmann function, a slowly developing "hump" appears in the ON-segment of the current record.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2212984 TI - Volume-activated chloride permeability can mediate cell volume regulation in a mathematical model of a tight epithelium. AB - Cell volume regulation during anisotonic challenge is investigated in a mathematical model of a tight epithelium. The epithelium is represented as compliant cellular and paracellular compartments bounded by mucosal and serosal bathing media. Model variables include the concentrations of Na, K, and Cl, hydrostatic pressure, and electrical potential, and the mass conservation equations have been formulated for both steady-state and time-dependent problems. Ionic conductance is represented by the Goldman constant field equation (Civan, M.M., and R.J. Bookman. 1982. Journal of Membrane Biology. 65:63-80). A basolateral cotransporter of Na, K, and Cl with 1:1:2 stoichiometry (Geck, P., and E. Heinz. 1980. Annals of the New York Academy of Sciences. 341:57-62.) and volume-activated basolateral ion permeabilities are incorporated in the model. MacRobbie and Ussing (1961. Acta Physiologica Scandinavica. 53:348-365.) reported that the cells of frog skin exhibit osmotic swelling followed by a volume regulatory decrease (VRD) when the serosal bath is diluted to half the initial osmolality. Similar regulation is achieved in the model epithelium when both a basolateral cotransporter and a volume-activated Cl permeation path are included. The observed transepithelial potential changes could only be simulated by allowing volume activation of the basolateral K permeation path. The fractional VRD, or shrinkage as percent of initial swelling, is examined as a function of the hypotonic challenge. The fractional VRD increases with increasing osmotic challenge, but eventually declines under the most severe circumstances. This analysis demonstrates that the VRD response depends on the presence of adequate intracellular chloride stores and the volume sensitivity of the chloride channel. PMID- 2212986 TI - Complete nucleotide sequence of clover yellow mosaic virus RNA. AB - The entire genomic RNA of clover yellow mosaic virus was sequenced from cDNA clones and run-off cDNA transcripts. The genomic RNA is 7015 nucleotides in length [excluding a 3' poly(A) tail], with six open reading frames (ORFs) greater than 150 nucleotides in length. The first five ORFs encode proteins of Mr 191K, 26K, 12K, 6.5K and 28K, respectively. The sixth ORF lies completely within ORF1 and codes for a protein of Mr 14K. The capsid protein coding region (Mr 23K) is found within ORF5 which encodes the Mr 28K protein. Proteins encoded by ORFs 1 to 3 and ORF5 show strong homology with proteins of other potexviruses, especially papaya mosaic virus. PMID- 2212985 TI - Nucleotide sequence and genomic organization of melon necrotic spot virus. AB - Cloned cDNA copies of the genomic RNA of melon necrotic spot virus (MNSV) have been sequenced and the sizes and locations of predicted viral proteins have been deduced. The genome consists of at least 4262 nucleotides and the positive strand contains three to five open reading frames (ORFs) which may be expressed. The 5' proximal ORF encodes a 29K protein (p29) and terminates with an amber codon which may be read through to produce an 89K protein (p89). Two small centrally located ORFs each encode a 7K protein (p7A and p7B). As p7A is in frame with p7B, readthrough of the amber codon terminating p7A may occur, producing a 14K protein (p14). The 3' proximal ORF encodes the 42K coat protein. The genomic organization of MNSV, its probable translation strategy and the amino acid sequences of its putative proteins closely resemble those of known carmoviruses, suggesting that MNSV should be classified as a member of the carmovirus group. Unusual properties of the putative MNSV replicase (p89) suggest that MNSV should be classified in a new virus supergroup with several other viruses sharing these properties. PMID- 2212987 TI - Molecular genetic analyses of the soybean mosaic virus NIa proteinase. AB - Recombinant DNA molecules containing cDNA to a soybean mosaic virus (SMV) RNA genome were constructed and partial nucleotide sequences determined for two cDNA inserts, pSMV-34 and pSMV-35. Comparison of the predicted amino acid sequence encoded by the pSMV-34 cDNA insert to other potyvirus protein sequences revealed extensive homology with the region of the genome encoding the NIa proteinase, with conservation of the amino acids proposed to form the catalytic triad of the active site. Cell-free transcription and translation of the cloned cDNA sequence containing the NIa open reading frame and flanking sequences revealed that NIa proteinase sequences, which were expressed as part of a high Mr precursor, were able to undergo proteolytic processing. Alteration of the codon for one of the putative active site residues by site-directed mutagenesis eliminated processing and resulted in the accumulation of a high Mr precursor. Based on predicted amino acid sequences at five putative cleavage sites within the SMV polyprotein, a consensus SMV NI a proteinase cleavage sequence of Glu/Asn-Xaa-Val-Xaa-Xaa-Gln decreases Gly/Ser was proposed. The SMV NIa proteinase and its putative cleavage sites maintained motifs found in other potyviruses. PMID- 2212989 TI - Proteolytic cleavage of microtubule-associated proteins by retroviral proteinases. AB - Aspartic proteinases from human immunodeficiency virus type 1 (HIV-1) and avian myeloblastosis virus (AMV) were found to interfere with microtubule assembly. Preincubation of the proteinases with purified brain microtubule proteins (tubulin and microtubule-associated proteins) at low ionic strength (pH 6.8), completely inhibited microtubule assembly. Analysis of microtubule proteins after incubation with proteinase showed no effect on tubulin but extensive cleavage of the microtubule-associated proteins 1 and 2 was observed. The digestion by the two proteinases differed. In the presence of HIV-1 proteinase, a fragment with an Mr of approximately 300, appeared, as well as at least three other new fragments, with Mr values of 188,000, 124,000 and 73,000. In the presence of AMV proteinase, the microtubule-associated proteins were extensively digested to many small fragments. The extending microtubule-associated proteins normally seen by electron microscopy on the microtubule surface disappeared after treatment with AMV proteinase. Our results show that retroviral proteinases are not restricted to cleavage of viral polyproteins in vitro. It is suggested that proteolysis of microtubular proteins by viral proteinases is an important step in viral pathogenicity and that it may be part of a mechanism causing degenerative effects in infected cells. PMID- 2212988 TI - Sulphoevernan, a polyanionic polysaccharide, and the narcissus lectin potently inhibit human immunodeficiency virus infection by binding to viral envelope protein. AB - Sulphoevernan is a sulphated alpha-1----3, 1----4 polyglucan (Mr 20,000) with a helical structure. This compound effectively inhibits both human immunodeficiency virus type 1 (HIV-1) and type 2 infection of cells in vitro at concentrations around 0.5 micrograms/ml. Moreover, the compound completely inhibits HIV-1 induced syncytium formation at a concentration of 1 microgram/ml. Competition experiments with 35S-labelled sulphoevernan revealed that the mannose-specific lectin from Narcissus pseudonarcissus prevented binding of sulphoevernan to HIV 1, whereas the antibody OKT4A did not reduce the amount of sulphoevernan bound to MT-2 cells. These data indicate that the non-cytotoxic polymer sulphoevernan binds to the virus rather than to the host cell. In vivo studies, using Rauscher leukaemia virus in NMRI mice, revealed that, at a daily dose of 20 mg/kg, the animals were protected against virus-induced increases in spleen weight. From these in vitro and in vivo data we conclude that sulphoevernan has potential in the treatment of acquired immunodeficiency syndrome. PMID- 2212990 TI - Rapid detection and further characterization of infection with hepatitis B virus variants containing a stop codon in the distal pre-C region. AB - Recently, hepatitis B virus (HBV) replication in the absence of HBe antigenaemia has been attributed to HBV variants with a TAG stop codon in the distal pre-C region associated with one or two point mutations. We describe here a rapid detection method for the diagnosis of such HBeAg-negative HBV variants using selective oligonucleotide hybridization. The entire pre-C region was amplified by the polymerase chain reaction and hybridized under stringent conditions with non mutated (M0), one (M1) and two (M2) point-mutated oligonucleotide probes. Of the 15 HBeAg-positive (group I) and 20 HBeAg-negative (group II) serum samples studied, 14 samples in group I and one sample in group II hybridized with M0 only and 18 samples in group II hybridized with M1 or M2, or both. The remaining two samples (from groups I and II, respectively) failed to hybridize with any of the three probes. DNA sequencing confirmed mixed distal pre-C sequences in samples hybridizing with more than one probe and also revealed novel mutations in the distal pre-C region of the two samples which failed to hybridize with any of the probes. The latter sample had a +2 frameshift and hence represented a new type of HBeAg-negative HBV variant. This method may therefore prove useful in the diagnosis of infections by HBeAg-negative HBV variants resulting from common mutations in the pre-C region, as well as for the identification of less common variants with novel mutations in the same region. PMID- 2212991 TI - DNA sequence of the gene encoding a major secreted protein of vaccinia virus, strain Lister. AB - Infection of tissue culture cells with vaccinia virus results in the specific secretion of several polypeptides into the medium. Previous studies identified a protein of approximate Mr 35,000 (35K) which was secreted in large amounts at both early and late times after infection with the Evans strain. We now show that a related protein is secreted by the Lister strain but not by WR, Wyeth nor Tian Tan. The gene encoding the Lister strain 35K protein was mapped within the inverted terminal repeats of the genome. The DNA sequence of this region showed that the ends of this gene are very similar to previously published sequences flanking a gene of WR which encodes a protein of approximate Mr 7,500 (7.5K). Our results suggest that the 7.5K polypeptide of WR may have arisen as a result of a deletion event and is a truncated form of the 35K Lister protein. Site-directed mutagenesis demonstrated that the 35K secreted protein encoded by Lister is not essential for growth in tissue culture. PMID- 2212992 TI - Immunological relationships of simian virus 41 (SV41) to other paramyxoviruses and serological evidence of SV41 infection in human populations. AB - Antigenic relationships of simian virus 41 (SV41) to other paramyxoviruses were examined by immunoprecipitation of isotope-labelled SV41-infected cell lysates with specific antisera. SV41 is closely related to the group comprising human parainfluenza virus 2 (HPIV-2), simian virus 5 (SV5), parainfluenza virus 4 and mumps virus. Slight cross-neutralization was detected between SV41, HPIV-2 and SV5. Anti-SV41 activities were detected in 21 of 1116 human serum specimens, indicating that a proportion of the human population is infected with SV41. The haemagglutinin-neuraminidase of SV41 was preferentially immunoprecipitated by anti-SV41 positive sera. PMID- 2212993 TI - Prediction and identification of a T cell epitope in the fusion protein of measles virus immunodominant in mice and humans. AB - Amino acid residues 288 to 302 of the fusion protein of measles virus were predicted by a variety of methods to represent a putative T cell epitope. This sequence was synthesized and the peptide was injected into mice of six inbred strains to test this possibility. Lymphocytes from peptide-immunized mice from all six H-2 disparate strains were able to mount a proliferative response following in vitro culture with the peptide. In addition, lymphocytes from three strains also proliferated in the presence of live measles virus. The peptide also behaved as a B cell epitope in that immunization with free peptide in adjuvant resulted in anti-peptide antibody production in all mouse strains. However, these antibodies did not react with the virus in either a solid-phase immunoassay or a virus neutralization assay. Peripheral blood lymphocytes from 10 laboratory personnel with a prior history of exposure to measles virus were tested in a proliferation assay with the peptide and with the virus. Lymphocytes from all 10 individuals proliferated in response to culture with the virus and those from eight responded to the peptide. These results give further support to the concept of permissive interaction of antigenic peptides with a wide range of class II major histocompatibility complex molecules both in mice and man and indicate the possibility of designing peptides that could be used as components of a synthetic vaccine for use in man. PMID- 2212994 TI - Persistent infection of a glioma cell line generates a Theiler's virus variant which fails to induce demyelinating disease in SJL/J mice. AB - Theiler's murine encephalomyelitis virus (TMEV) induces demyelinating disease which is associated with persistent virus infection of the central nervous system. To study the interaction between TMEV and host cells, we infected the G26 20 glioma cell line in vitro, and this resulted in a lytic infection in which most, but not all, cells were killed. Surviving cells divided and formed a viable monolayer in which a small proportion of cells displayed viral cytopathic effects. Levels of virus produced by these cultures over a 6 month period fluctuated between 6 and 8 log10 p.f.u./ml as measured by viral plaque assay. Similarly, the percentage of cells producing both viral antigen and viral RNA, as measured by a simultaneous immunoperoxidase/in situ hybridization technique, varied between 5 and 30%. Although persistently infected cultures were susceptible to challenge by both vesicular stomatitis virus and herpes simplex virus, they were resistant to infection by homologous viruses. Interferon activity was not identified. TMEV isolated from passage 12 produced smaller plaques than wild-type Daniels strain virus (wt-DAV) on L-2 cell monolayers. In contrast to demyelination induced in SJL/J mice after intracerebral inoculation with wt-DAV, mice infected with the small plaque variant virus failed to develop viral persistence or chronic demyelination. However, following immunosuppression by total body irradiation, SJL/J mice infected with the small plaque variant developed viral persistence but no demyelination. Characterization of the biochemical and molecular determinants of the variant will lead to a better understanding of determinants important in viral persistence. PMID- 2212995 TI - Terminal redundancy and circular permutation of mycoplasma virus L3 DNA. AB - This communication reports the physical map of mycoplasma virus L3 (MV-L3) DNA derived from restriction patterns obtained by digestion with seven different restriction endonucleases. The length of the restriction map is 36,200 bp in contrast to the contour length of native MV-L3 DNA molecules which is 39,400 bp as determined by electron microscopy. The difference in length of 3,200 bp (corresponding to 8.1% of the native viral DNA contour length) is explained by terminal redundancy. It was possible to clone all fragments from particular restriction patterns into Escherichia coli vector pAT153, an indication of circular permutation within a population of MV-L3 DNA. However clear evidence has been obtained from the molar ratios of fragments and from hybridization experiments. We suppose that viral DNA is packaged from a concatemeric precursor molecule starting at a specific site called pac. PMID- 2212996 TI - Transgenic Nicotiana debneyii expressing viral coat protein are resistant to potato virus S infection. AB - The coat protein gene from potato virus S (PVS) was introduced into Nicotiana debneyii by leaf disc transformation using Agrobacterium tumefaciens. Transgenic plants expressing the viral coat protein were highly resistant to subsequent infection by the ME strain of PVS as indicated by an absence of symptom development and a lack of accumulation of virus in both the inoculated and upper leaves. As in reported experiments with plants expressing potato virus X coat protein, plants expressing PVS coat protein were also protected from inoculation with PVS RNA. These results provide further evidence that coat protein-mediated protection for these two groups of viruses, which share similar genome organizations, may involve inhibition of some early event in infection other than or in addition to virus uncoating. PMID- 2212997 TI - Influenza B virus mRNA synthesis in vivo: efficient transcription of vRNAs 1, 2 and 3. AB - Influenza B virus genomic RNA (vRNA) segments encoding polymerase proteins were shown to be efficiently transcribed in vivo, unlike those of influenza A virus. The results are discussed in connection with the primary structure of the 3' ends of vRNA segments. PMID- 2212998 TI - Perception of childhood dissatisfaction with parents and selected personality traits in adulthood. AB - This study tested the hypotheses that perceptions of childhood dissatisfaction with parents are associated with higher scores on measures of intensity and chronicity of loneliness, anxiety, neuroticism, psychoticism, misanthropy, and external locus of control and lower scores on measures of self-esteem and sociability. The subjects were 537 Iranian students studying in American and Iranian universities. Both hypotheses were confirmed in a multivariate statistical model. We also found that dissatisfaction with parents was related to a lack of satisfactory relationships with peers. PMID- 2212999 TI - Development of reference and working spatial memory in preschool children. AB - Three groups of preschool children (aged 18 to 28, 33 to 42, and 47 to 58 months) were given a radial search test similar to the radial arm maze used with nonhuman subjects. The children searched for chocolate sweets among 10 labeled locations in a room, 5 of which were baited with a sweet. Older children outperformed the intermediate group, who in turn outperformed the youngest group in requiring fewer choices to retrieve all of the sweets. Working memory and reference memory aspects of performance were then separated: Reference memory (restriction of choices to the baited subset) in older children was superior to that in the youngest group but not to that in the intermediate group. In terms of working memory (avoidance of repeat responses to already visited locations), the older group made fewer errors than the intermediate group, who, in turn, made fewer errors than the youngest group. We concluded that working and reference components of spatial memory in children may share common elements, perhaps the ability to recognize places as familiar, although reference memory may develop earlier than working memory. PMID- 2213000 TI - A test of perceptual enhancement with peripherally presented letter pairs. AB - The present study was conducted to determine whether sensitivity to a member of a pair of stimulus letters projecting to the parafovae would be improved by presenting that member at fixation. The effect was examined for the pair member appearing at a constant distance from fixation, which always was flanked to its inner or outer side. Contrary to expectations based upon results reported by Geiger and Lettvin (1986), observed accuracy changes were found to be due to response bias rather than to sensitivity enhancement. PMID- 2213001 TI - A comparison of concept formation strategies in pattern recognition tasks. AB - We used two experiments to explore the effects of two kinds of strategies (nonanalytic and analytic) in concept formation. In Experiment 1, nonsense shapes were used as stimuli, which created ill-defined categories of concepts to be discovered by the subjects. In Experiment 2, highly recognizable geometrical patterns were used as stimuli, hereby placing an emphasis on the identification of highly salient categories of concepts. Subjects were better able to classify stimuli correctly in both experiments relying on memory (nonanalytic strategy) than on rule learning (analytic strategy). Here we discuss implications of nonanalytic strategy for understanding the nature of creativity. PMID- 2213002 TI - The use of the orthographic lexicon in reading kana words. AB - A lexical decision task was used to investigate the dual-route hypothesis that, in reading words conventionally written in katakana, a Japanese syllabic script, lexical access may be achieved by both a process of assembled segmental phonology and the use of a visual orthographic lexicon. The variables examined were lexicality (words and nonwords), kana type (katakana and hiragana), string length (long and short), and vocal interference (silence and concurrent vocalization). The main effects of the first three variables were significant, but more important, we found that subjects could be divided into two groups--phonological assemblers and orthographic lexicon users. Words that assume sighting were also identified. Collectively, the results were interpreted to uphold the dual-route hypothesis and to reject the common view that kana words are accessed on the basis of phonological mediation alone. PMID- 2213003 TI - Lateral imbalance of the visual field affects conjugate lateral eye movement: an experimental demonstration. AB - Baker (1989) reported a serendipitous observation: When subjects were seated closer to the left than to the right wall of the room, conjugate lateral eye movement (CLEM) following a question involving shared eye gaze was predominantly toward the right. This study sought to verify this observation. In the asymmetrical condition, half the subjects sat next to the right wall and the other half sat next to the left wall. In the symmetrical condition, each subject was seated equidistantly from the right and left walls. More CLEM was found in asymmetrical conditions in the direction toward the center of the wall the subject faced, a finding consistent with the earlier formulations and findings of the sensory-tonic theory of perception. PMID- 2213004 TI - Differential expression of mRNA and protein encoding retinal and pineal S-antigen during the light/dark cycle. AB - S-Antigen is a soluble cell protein unique to the retina and pineal gland. In the former, it is a well-characterized molecule that participates in light-induced signal transduction in photoreceptor cells. In the latter, the functional role is presently not known. The expression of S-antigen and its mRNA was examined in the rat retina and pineal gland throughout the diurnal cycle and with light interruption of the dark cycle. A cDNA for rat S-antigen was isolated from a pineal gland library to examine the mRNAs. A 1.7-kb mRNA for S-antigen was observed in both the pineal gland and the retina. Retinal S-antigen mRNA was expressed throughout the diurnal cycle and increased with light interruption of the dark cycle. In contrast, pineal gland S-antigen mRNA levels were detectable only during the dark and were absent preceding and during light. The phenotypic expression of immunoreactive S-antigen, identified with two S-antigen monoclonal antibodies (MAbs), MAb A9C6 and MAb C10C10, was analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel (PAGE) and isoelectric focusing (IEF) electrophoresis. Immunoblot analysis of gels after SDS-PAGE revealed a single 46 kDa protein in retina. In contrast, two bands of approximately 43 and 46 kDa were identified in the pineal gland. Immunoblots of the retinal extracts separated by IEF electrophoresis revealed five S-antigen isomers, which vary quantitatively throughout the diurnal cycle and when light interrupted the dark cycle. Immunoblots of the pineal gland samples separated by IEF electrophoresis indicated that the pineal gland possesses four pineal gland-specific forms of S antigen in addition to the five forms present in the retina. The differences observed in the mRNA and protein analyses suggest tissue-specific structural components for S-antigen in the retina and pineal gland that are not regulated in the same manner. PMID- 2213005 TI - Reversible inhibition of acetylcholine synthesis and behavioural effects caused by 3-bromopyruvate. AB - 3-Bromopyruvate inhibits pyruvate decarboxylase in brain homogenates and causes a 90% drop in acetylcholine tissue content at a concentration of 2 mM. Stereotaxic injection of 3-bromopyruvate into the basal forebrain causes after 7 days a 40% drop of acetylcholine concentration and pyruvate decarboxylase activity in the cortex and hippocampus, and greater decreases at the site of injection. However, values return to normal 18 days after injection. Choline acetyltransferase is partially inhibited only at the site of injection after 7 days. Choline transport and choline concentration are not affected at either 7 or 18 days after injection. Impairments in spontaneous alternation and in retention of passive avoidance were seen only 7 days after the injection. The results suggest that stereotaxic injection of bromopyruvate can induce discrete reversible cholinergic lesions on a time scale useful for behavioural experiments and for comparison with neurodegeneration. PMID- 2213006 TI - Different ceramide compositions of gangliosides between human motor and sensory nerves. AB - Ganglioside analysis of human motor and sensory nerves revealed that ceramide compositions of sensory nerve GD1a, GD1b, and GM1 differed apparently from those in the motor nerve. These gangliosides from sensory nerve contained a large amount of long-chain fatty acids and d18:1 as a major long chain base. On the contrary, the motor nerve gangliosides contained C16-18 fatty acids and a large amount of d20:1 besides d18:1. Furthermore, these gangliosides were enriched more in the axon fraction than in the myelin fraction. LM1, which was a major ganglioside in myelin from human peripheral nerve, was composed of similar ceramide compositions in the two nerves. The present findings suggest that the characteristic ceramide species of nerve gangliosides may reflect in part properties of their own neurons. PMID- 2213007 TI - Brain and plasma tetrahydroisoquinolines in rats: effects of chronic ethanol intake and diet. AB - Brain concentrations of salsolinol (SAL), a simple tetrahydroisoquinoline (sTIQ) condensation product of dopamine (DA) and acetaldehyde, are reported to increase in chow-fed rats drinking ethanol/H2O ad libitum. However, our analyses showed that rat chow contains traces of SAL and, as previously reported, appreciable 3,4 dihydroxyphenylalanine (DOPA), a sTIQ precursor. To examine the effect of consumption of ethanol in a DOPA- and SAL-free diet on endogenous sTIQs, we analyzed two brain regions and blood plasma of rats undergoing prolonged intake (3 weeks and 23 weeks) of liquid diet containing 6.6% ethanol or isocaloric carbohydrate. SAL and three other DA-related sTIQs were quantitated using capillary gas chromatography/mass spectrometry in the selected ion mode with deuterated standards. In accord with studies on ethanol/chow-fed rats, sTIQ concentrations in hypothalamus were elevated after 3 weeks of ethanol, although after 23 weeks, hypothalamic sTIQs were either unchanged or reduced (O-methylated SAL). Furthermore, sTIQ concentrations in corpus striatum and, with one exception, plasma were not altered by ethanol ingestion for either duration. (However, 23 weeks of ethanol intake significantly reduced the striatal concentrations of DA and its acid metabolite, presumably reflecting neurotoxicity.) Reasoning that DOPA in diet might underlie the reported ethanol dependent increases in striatal sTIQs, we found that L-DOPA supplementation (500 micrograms/rat/day) of EtOH/liquid diet-fed rats for 13 weeks tended to increase striatal SAL. Overall, the data indicate that elevations in endogenous sTIQ concentrations due to prolonged ethanol intake depend on the brain region, duration of intake, and even associated dietary constituents. In that regard, the higher striatal SAL concentrations in rats drinking ethanol ad libitum could have been facilitated by DOPA and perhaps SAL consumed in lab chow. PMID- 2213009 TI - Manipulation of plasma membrane fatty acid composition of fetal rat brain cells grown in a serum-free defined medium. AB - Modifications of plasma membrane acyl-linked phospholipid fatty acid composition were produced by supplementing the culture medium with essential fatty acids. The plasma membrane fraction was purified by Percoll gradient centrifugation from dissociated fetal rat brain cells grown in a serum-free culture medium. Both the concentration dependence and the time course of the modifications were examined. Supplementation of the medium with essential polyunsaturated fatty acid, linolenic acid (18:3 omega 3) or linoleic acid (18:2 omega 6), produced incorporation of the elongated and desaturated products of omega 3 or omega 6 class, respectively, i.e., the incorporation was class specific. Within each class, the most unsaturated and elongated members, i.e., terminal members, were preferentially incorporated until they reached a maximum concentration within 6-7 days. At higher concentrations of supplemented fatty acids, additional class specific incorporation in plasma membrane was produced by an increase in the concentration of intermediate members. At the same time, the concentration of monounsaturated fatty acids declined and that of saturated fatty acids remained unchanged. The modifications in fatty acid composition were reversible, with the time course similar to that of incorporation. The total plasma membrane phospholipid and sterol contents did not change with alterations of fatty acid composition, but did change with time in culture. This preparation should prove useful for investigating the role of polyunsaturated fatty acids in brain cell functions, including neuronal excitability. PMID- 2213008 TI - Physicochemical properties of serotonin 5-HT3 binding sites solubilized from membranes of NG 108-15 neuroblastoma-glioma cells. AB - Specific binding sites with pharmacological properties typical of serotonin 5-HT3 receptors were identified in membranes of the murine hybridoma cell line NG 108 15, using [3H]zacopride as a ligand. Optimal solubilization of these sites (yield, 50%) could be achieved using the detergent 3-[3 (cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS) at 24 mM plus 0.5 M NaCl in 25 mM Tris-HCl, pH 7.4. Specific [3H]zacopride binding to soluble sites in the 100,000-g CHAPS extract was saturable and showed characteristics (Bmax = 425 +/- 81 fmol/mg of protein; KD = 0.19 +/- 0.02 nM) closely related to those of membrane-bound sites (Bmax = 932 +/- 183 fmol/mg of protein; KD = 0.60 +/- 0.03 nM). Determination of association (k+1 = 0.17 nM min-1) and dissociation (k-1 = 0.02 min-1) rate constants for the soluble sites gave a KD value of 0.12 nM, a result consistent with that calculated from saturation studies. As assessed from the displacement potencies (IC50) of 10 different drugs, the pharmacological profile of [3H]zacopride specific binding sites was essentially the same (r = 0.99) in the CHAPS-soluble extract and in cell membranes, although some increase in the affinity for 5-HT3 antagonists (zacopride, ICS 205-930, and MDL 72222) and decrease in the affinity for 5-HT3 agonists (2-methyl-5-hydroxytryptamine and phenylbiguanide) were noted for the soluble sites. Sucrose density gradient sedimentation of the CHAPS-soluble extract gave a Svedberg coefficient of 12S for the material with [3H]zacopride specific binding capacity. Chromatographic analyses using Sephacryl S-400 and wheat germ agglutinin-agarose columns indicated marked enrichment (by 2.5- and 10-fold, respectively) in [3H]zacopride specific binding activity in the corresponding eluates compared with the starting soluble extract, a finding suggesting that both steps are of potential interest for the partial purification of solubilized 5-HT3 receptors. Two soluble materials with apparent molecular masses of approximately 600 and approximately 36 kDa were found to bind [3H]zacopride specifically in the Sephacryl S-400 eluate. Interestingly, molecular mass determination by radiation inactivation of [3H]zacopride binding sites in frozen NG 108-15 cells gave a value of approximately 35 kDa. PMID- 2213010 TI - Solubilization of the membrane-bound sialidase from pig brain by treatment with bacterial phosphatidylinositol phospholipase C. AB - The total pellet from pig forebrain (from which the cytosolic sialidase was completely washed out) was treated with phosphatidylinositol phospholipase C (PIPLC) and centrifuged at high speed. The supernatant contained sialidase and 5' nucleotidase activities. The greatest liberation of sialidase was obtained after incubation for 20 min with PIPLC at 37 degrees C using pH 6.0 and a ratio between PIPLC (as units) and protein of 1.6. Under these conditions, the release of sialidase, 5'-nucleotidase, and protein was 22, 50, and 18.5%, respectively. On treatment with PIPLC, a purified preparation of pig brain neuronal (synaptosomal) membranes released 28% of its sialidase whereas a purified preparation of pig brain lysosomes did not liberate any sialidase activity. The pH optimum of sialidase present in the supernatant obtained after PIPLC treatment of the total pellet was 4.2, the same as that of the enzyme embedded in the membrane. When this supernatant was subjected to ammonium sulfate fractionation, 88% of its sialidase, having a pH optimum of 4.2, was recovered in the fraction precipitated between 20 and 45% of salt saturation and subsequently dialyzed. Ammonium sulfate treatment caused the appearance of a second sialidase activity, having a pH optimum of 6.6 and behaving on fractionation similarly to the pH 4.2 sialidase. The Km and Vmax values of pH 4.2 and pH 6.6 sialidase were similar (1.48 x 10(-4) and 0.98 x 10(-4) M for Km and 1.6 and 1.4 mU/mg of protein for Vmax, respectively), whereas the stability on standing at 4 degrees C or exposure to freezing and thawing cycles was greater for pH 4.2 sialidase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213011 TI - Detection of cystathionine ketimine in bovine cerebellum. AB - A new sulfur-containing cyclic imino acid, cystathionine ketimine, has been detected in bovine cerebellum by gas chromatography, gas chromatography-mass spectrometry, and high pressure liquid chromatography procedures. Gas chromatography and gas-mass analyses are based on derivatization of endogenous cystathionine ketimine with diazomethane after a simple enrichment procedure. The high pressure liquid chromatography procedure takes advantage of the selective absorbance at 380 nm of the phenyl isothiocyanate-ketimine interaction product. The concentration of this new sulfur imino acid found in a pool of four bovine cerebella is approximately 0.5 nmol/g. PMID- 2213012 TI - Analysis of adenosine immunoreactivity, uptake, and release in purified cultures of developing chick embryo retinal neurons and photoreceptors. AB - We have investigated the presence of endogenous adenosine and of mechanisms for adenosine uptake and release in chick embryo retinal neurons and photoreceptors grown in purified cultures in the absence of glial cells. Simultaneous autoradiographic and immunocytochemical analysis showed that endogenous adenosine and the uptake mechanism for this nucleoside colocalize in practically all the photoreceptors, but only in approximately 20% of the neurons. Approximately 25% of the neurons showed either immunocytochemical labeling or autoradiographic labeling, while greater than 50% of the neurons were unlabeled with both techniques. [3H]Adenosine uptake was saturable and could be inhibited by nitrobenzylthioinosine and dipyridamole and by pretreatment of the [3H]adenosine with adenosine deaminase. Although these observations indicate that the uptake is specific for adenosine, only 35% of accumulated radioactivity was associated with adenosine, with the remaining 65% representing inosine, hypoxanthine, and nucleotides plus uric acid. Adenosine as well as several of its metabolites were released by the cells under basal as well as K(+)-stimulated conditions. Potassium-enhanced release was blocked by 10 mM CoCl2 or in Ca2(+)-free, Mg2(+) rich solutions. The results indicate that retinal cells that synthesize, store, and release adenosine differentiate early during embryogenesis and are therefore consistent with a hypothetical role for adenosine in retinal development. PMID- 2213013 TI - Biexponential kinetics of (R)-alpha-[3H]methylhistamine binding to the rat brain H3 histamine receptor. AB - The H3 histamine receptor is a high-affinity receptor reported to mediate inhibition of CNS histidine decarboxylase activity and depolarization-induced histamine release. We have used (R)-alpha-[3H]methylhistamine, a specific, high affinity agonist, to characterize ligand binding to this receptor. Saturation binding studies with rat brain membranes disclosed a single class of sites (KD = 0.68 nM; Bmax = 78 fmol/mg of protein). Competition binding assays also yielded an apparently single class of sites with a rank order of potency for ligands characteristic of an H3 histamine receptor: N alpha-methylhistamine, (R)-alpha methylhistamine greater than histamine, thioperamide greater than impromidine greater than burimamide greater than dimaprit. In contrast, kinetic studies disclosed two classes of sites, one with fast, the other with slow on-and-off rates. Density of (R)-alpha-[3H]methylhistamine binding followed the order: caudate, midbrain (thalamus and hippocampus), cortex greater than hypothalamus greater than brainstem greater than cerebellum. These data are consistent with an H3 histamine receptor, distinct from H1 and H2 receptors, that occurs in two conformations with respect to agonist association and dissociation or with multiple H3 receptor subtypes that are at present pharmacologically undifferentiated. PMID- 2213014 TI - Endogenous release of gamma-aminobutyric acid from the medial preoptic area measured by microdialysis in the anaesthetised rat. AB - The characteristics of gamma-aminobutyric acid (GABA) release as monitored by microdialysis have been investigated in the chloral hydrate anaesthetised rat. The high outflow of GABA following insertion of the microdialysis probe (membrane 2 mm in length, 0.5 mm in diameter) into the medial preoptic area was found to decline to a stable baseline level after 2 h. After this time, perfusion with a medium containing 100 mM potassium ions evoked a 56-fold increase in GABA outflow. The addition of the calcium channel blocker verapamil (100 microM) to the perfusion medium induced significant 25 and 50% reductions in basal and potassium-stimulated GABA outflow, respectively. In the same animals, verapamil caused an 80% decrease in potassium-stimulated noradrenaline outflow. The glutamic acid decarboxylase inhibitors 3-mercaptopropionic acid and L allylglycine added to the perfusion medium at a concentration of 10 mM reduced basal GABA release by approximately 50% with different time-courses of action. Ethanolamine-O-sulfate, a GABA-transaminase inhibitor, induced significant increases in basal GABA outflow 90 min after inclusion in the perfusion medium. These results demonstrate that microdialysis is a suitable technique with which to monitor extracellular levels of GABA and provide in vivo data on GABA release and degradation mechanisms. PMID- 2213015 TI - Enzyme activities in relation to pH and lactate in postmortem brain in Alzheimer type and other dementias. AB - Phosphate-activated glutaminase, glutamic acid decarboxylase, pyruvate dehydrogenase, succinic dehydrogenase, pH, and lactate were measured in frontal cortex and caudate nucleus of postmortem brains from cases of Alzheimer-type dementia (ATD), Down's syndrome, Huntington's disease, and one case of Pick's disease, as well as from sudden death and agonal controls. Lactate levels were higher and pH, phosphate-activated glutaminase, and glutamic acid decarboxylase levels were lower in the agonal controls than in the sudden death controls. Phosphate-activated glutaminase and glutamic acid decarboxylase were correlated with tissue pH and lactate, and also were reduced by in vitro acidification, suggesting that the low activities of these enzymes in agonal controls were related to decreased pH consequent upon lactate accumulation. Compared with control tissues at the same pH, phosphate-activated glutaminase and glutamic acid decarboxylase were unaltered in ATD and Down's frontal cortex and reduced in Huntington's caudate nucleus, and glutamic acid decarboxylase was reduced in Huntington's frontal cortex. These data suggest that GABAergic neurons are not affected in ATD and confirm the GABAergic defect in Huntington's disease. Pyruvate dehydrogenase and succinic dehydrogenase activities were the same in agonal controls and sudden death controls and were unaffected by acid pH and lactate in vitro, and pyruvate dehydrogenase was not correlated with pH or lactate. Reduced pyruvate dehydrogenase in frontal cortex of individual ATD, Down's, and Pick's cases, and in the caudate nucleus of Huntington's and Down's cases, was accompanied by gliosis/neuron loss. We conclude that decreased pyruvate dehydrogenase reflects neuronal loss. PMID- 2213016 TI - [3H]thienylcyclohexylpiperidine binding activity in brain synaptic membranes treated with Triton X-100. AB - Binding activity of [3H]thienylcyclohexylpiperidine was examined using rat brain synaptic membranes treated with Triton X-100. This compound is proposed to be a noncompetitive antagonist for the N-methyl-D-aspartate (NMDA)-sensitive subclass of brain excitatory amino acid receptors. The activity decreased in proportion to increasing concentrations of the detergent up to 0.08%. In vitro addition of L glutamate (Glu) partially restored the decreased activity caused by this Triton treatment, whereas further addition of glycine (Gly) entirely reversed the loss of activity to the level found in membranes extensively washed but not treated with a detergent. These stimulatory effects were found to be due to the acceleration of the association of ligand. The rank order of potentiation of the activity coincided well with that of the affinity for the NMDA-sensitive subclass among numerous Glu analogs. The potentiation by Gly as well as Glu was invariably prevented by competitive NMDA antagonists, such as DL-2-amino-5-phosphonovalerate and (+/-)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate, but not by strychnine. No significant difference was observed between pharmacological profiles of the activities in synaptic membranes treated and not treated with Triton X-100, except haloperidol. The potency of this sigma-ligand to inhibit the activity was greatly reduced by the Triton treatment in the presence of both Glu and Gly. These results suggest that the regulatory properties of Triton-treated synaptic membranes remain unchanged in terms of the interaction within the NMDA receptor complex. PMID- 2213017 TI - Synthesis of urokinase-type plasminogen activator and of type-1 plasminogen activator inhibitor in neuronal cultures of human fetal brain: stimulation by phorbol ester. AB - Human neuronal brain cultures established from 12- and 14-week-old fetuses synthesize and secrete urokinase-type plasminogen activator (uPA) and limited amounts of tissue-type plasminogen activator (tPA). These cells also produce and secrete the endothelial cell-type PA inhibitor (PAI-1), which forms sodium dodecyl sulfate-stable tPA/PAI-1 complexes in the culture medium. Immunocytochemistry shows a predominant localization of uPA, tPA, and PAI-1 in neuronal cells, with only a very weak positivity detectable in the few glial cells present in these cultures. The protein kinase C (PKC) activator 12-O tetradecanoylphorbol 13-acetate (TPA) stimulates the synthesis of both uPA and PAI-1, resulting in a final increase in the plasmin-generating capacity of neuronal cell cultures. No significant effect is observed, however, when cells are treated with the TPA analogue 4 alpha-phorbol 12,13-didecanoate, which is inactive as a PKC inducer, or with the neurotrophic polypeptide basic fibroblast growth factor. These data represent the first characterization of the plasmin generating system in human fetal brain neurons and suggest a role for PKC in the modulation of uPA and PAI-1 synthesis. PMID- 2213018 TI - Neuronal intermediate filament expression during neurite outgrowth from explanted goldfish retina: effect of retinoic acid. AB - Regulation of the goldfish neuronal intermediate filament proteins ON1 and ON2 was investigated in a retinal explant system. The synthesis of these proteins in explanted retina decreased with increasing time in culture, despite continuing neurite outgrowth. Thus, ON1/ON2 neurofilament expression is regulated independently from neurite outgrowth. During regeneration of the goldfish optic nerve in vivo, the expression of these proteins increased during the later phase of the process, when growing axons make contact with the optic tectum. The declining synthesis of ON1 and ON2 during neurite outgrowth in culture suggests that factors extrinsic to the retina are necessary to support synthesis of these proteins. Treating retinal explants with retinoic acid stimulated the synthesis of the ON1/ON2 proteins in a dose-dependent manner. This stimulation was effective during a period of declining synthesis of the ON1/ON2 proteins, restoring their synthesis towards initial levels of expression. These results show that retinoic acid serves as a modulator of neurofilament expression in this in vitro model of nerve regeneration. PMID- 2213019 TI - Interaction of the two structural domains of calmodulin with mature and immature rat brain microtubules. AB - The inhibitory effect of calmodulin on the assembly of mature and immature rat brain microtubules was compared with that of the two major structural domains of this protein, the COOH-terminal fragment (amino acids 78-148) and the NH2 terminal fragment (amino acids 1-77), to determine the calmodulin structural domain responsible for the inhibitory effect on microtubule assembly. Microtubules prepared during the early stages of brain development, i.e., during intensive neurite outgrowth, are more sensitive to inhibition by the Ca2(+) calmodulin complex than those obtained from adult brain. Significant inhibition of immature microtubule assembly was observed with both fragments in the absence of Ca2+, but the effects were more important when Ca2+ was present. With adult brain microtubules, the two fragments remained without effect on assembly in the absence of Ca2+, whereas some inhibition was seen in its presence but only with the COOH-terminal polypeptide. Under all these conditions, the COOH-terminal fragment was always more active than the NH2-terminal fragment on microtubule polymerization, albeit to a lesser extent than native calmodulin. PMID- 2213020 TI - Phosphorylase alpha and labile metabolites during anoxia: correlation to membrane fluxes of K+ and Ca2+. AB - The objective of the present study was to explore mechanisms responsible for activation of ion conductances in the initial phases of brain ischemia, particularly for the early release of K+ that precedes massive cell depolarization, and rapid downhill fluxes of K+, Na+, Cl-, and Ca2+. As it has been speculated that a K+ conductance can be activated either by an increase in the free cytosolic calcium concentration (Ca2+i) or by a fall in ATP concentration, the question arises whether the early increase in extracellular K+ concentration (K+e) is preceded by a rise in Ca2+i and/or a fall in ATP content. In the present experiments, ischemia was induced in rats by cardiac arrest, the time courses of the rise in K+e and cellular depolarization were determined by microelectrodes, and the tissue was frozen in situ through the exposed dura for measurements of levels of labile metabolites. including adenine nucleotides and cyclic AMP (cAMP), after ischemic periods of 15, 30, 60, and 120 s. Conversion of phosphorylase b to a was assessed, because it depends, among other things, on changes in Ca2+i. The K+e value rose within a few seconds following induction of ischemia, but massive depolarization (which is accompanied by influx of calcium) did not occur until after approximately 65 s. Activation of phosphorylase was observed already after 15 s and before glycogenolysis had begun. At that time, 3',5'-cAMP concentrations were unchanged, and total 5'-AMP concentrations were only moderately increased. The results demonstrate that a K+ conductance is activated at a time when the overall ATP concentration remains at 95% of control values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213021 TI - Changes in glycosaminoglycans during the neuritogenesis in PC12 pheochromocytoma cells induced by nerve growth factor. AB - Previously, we had suggested that heparan sulfate (HS) makes some contribution to a flat-shaped morphology of PC12D cells. Therefore, we carried out quantitative and qualitative analyses of glycosaminoglycans (GAGs), the polysaccharide moiety of proteoglycans, during neuritogenesis in PC12 cells that is induced by nerve growth factor (NGF). (a) In PC12 cells, NGF induced a flat-shaped morphology with a few short processes after 3 days of culture, and then it elicited short and long neurites after 6 (in approximately 30% of cells) and 9 (in 60-70%) days of culture, respectively. (b) HS and chondroitin sulfate (CS) were detected in the cell layer at all times. Only CS was found in the medium at 3 and 6 days, whereas a low level of HS, in addition to CS, was detectable on day 9. (c) In the NGF treated cultures, the amounts of cell-associated HS per cell were two to three times as high as those in the respective nontreated cultures at all times, whereas the amount based on phospholipid was about twofold higher after 3 days of culture. (d) The levels of HS labeled with [35S]sulfate during the last 48 h of the culture were 1.5- to twofold higher in the NGF-treated cultures than in the respective controls at any time. (e) The amount of cell-associated CS per cell (or per unit of phospholipid), but not of labeled CS per cell, was transiently enhanced at 3 days in culture with or without NGF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213022 TI - Acetylcholine translocating protein: mediatophore at rat neuromuscular synapses. AB - The neuromuscular synapses of the rat sternomastoid muscles contain a membrane protein, mediatophore, that endows artificial membranes with a calcium-dependent acetylcholine release mechanism. Mediatophore and choline acetylase had similar distributions along the muscle. Sciatic nerve membranes contain mediatophore, and a purified preparation was obtained from the nerve. PMID- 2213023 TI - Binding of the adenosine A2 receptor ligand [3H]CGS 21680 to human and rat brain: evidence for multiple affinity sites. AB - A new radiolabeled adenosine receptor agonist, 2-[p-(2 carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadeno sin e (CGS 21680), apparently specific for high-affinity binding sites of the A2 subtype in rat brain, was used to identify and pharmacologically characterize adenosine receptors in human brain. The binding of [3H]CGS 21680, as determined by standard radioligand binding technique in the presence of exogenously added adenosine deaminase, reached equilibrium after 40 min at 25 degrees C. In saturation studies, a single class of high-affinity binding sites with values for KD of 22 +/- 0.5 nM and Bmax of 444 +/- 63 fmol/mg of protein were observed. Similar binding characteristics were observed regardless of whether rapid filtration or centrifugation was used to separate bound versus free ligand. Of the 14 brain regions examined, [3H]CGS 21680 binding was highest in putamen, followed by globus pallidus and caudate nucleus. The level of [3H]CGS 21680 binding in these areas of basal ganglia was identical to 5'-N-[3H]ethylcarboxamidoadenosine ([3H]NECA) binding in the presence of 50 nM N6-cyclopentyladenosine (CPA). The rank order of agonist potencies as determined by a series of competition experiments was NECA greater than or equal to CGS 21680 greater than 2 chloroadenosine greater than N6-(R)-phenylisopropyladenosine greater than N6 cyclohexyladenosine greater than N6-(S)-phenylisopropyladenosine. This potency order was the same for the binding of [3H]CGS 21680 to rat, and of [3H]NECA in the presence of 50 nM CPA to rat and human, brain membranes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213024 TI - Dynamics of phosphorylation and assembly of the high molecular weight neurofilament subunit in NB2a/d1 neuroblastoma. AB - In neuronal systems thus far studied, newly synthesized neurofilament subunits rapidly associate with the Triton-insoluble cytoskeleton and subsequently undergo extensive phosphorylation. However, in the present study we demonstrate by biochemical and immunological criteria that NB2a/d1 neuroblastoma cells also contain Triton-soluble, extensively phosphorylated 200-kDa high molecular weight neurofilament subunits (NF-H). High-speed centrifugation (100,000 g) of the Triton-soluble fraction for 1 h sedimented some, but not all, soluble NF-H subunits; immunoelectron microscopic analyses of the resulting pellet indicated that a portion of the NF-H subunits in this fraction are assembled into (Triton soluble) neurofilaments. When cells were pulse labeled for 15 min with [35S]methionine, radiolabel was first associated with the Triton-soluble 200-kDa NF-H variants. Because only extensively phosphorylated NF-H subunits migrate at 200 kDa, whereas hypophosphorylated subunits migrate instead at 160 kDa, these findings suggest that some newly synthesized subunits were phosphorylated before they polymerized. In pulse-chase analyses, radiolabeled 200-kDa NF-H migrated into the 100,000 g particulate fraction of Triton-soluble extracts before its arrival in the Triton-insoluble cytoskeleton. Undifferentiated cells, which do not possess axonal neurites and lack a significant amount of Triton-insoluble, extensively phosphorylated NF-H, contain a sizeable pool of Triton-soluble extensively phosphorylated NF-H subunits and polymers. We interpret these data to indicate that the integration of newly synthesized NF-H into the cytoskeleton occurs in a progression of distinct stages, and that assembly of NF-H into neurofilaments and integration into the Triton-insoluble cytoskeleton are not prerequisites for the incorporation of certain phosphate groups on these polypeptides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213025 TI - Ca2+ mobilized by caffeine from the inositol 1,4,5-trisphosphate-insensitive pool of Ca2+ in somatic regions of sympathetic neurons does not evoke [3H]norepinephrine release. AB - The effects of electrical stimulation, muscarinic and serotonergic agonists, and caffeine on [3H]inositol 1,4,5-trisphosphate ([3H]Ins(1,4,5)P3) content, intracellular free Ca2+ concentration ([Ca2+]i), and release of [3H]norepinephrine ([3H]NE) were studied in cultured sympathetic neurons. Neuronal cell body [Ca2+]i was unaffected by muscarinic or serotonergic receptor stimulation, which significantly increased [3H]Ins(1,4,5)P3 content. Stimulation at 2 Hz and caffeine had no effect on [3H]Ins(1,4,5)P3, but caused greater than two-fold increase in [Ca2+]i. Only 2-Hz stimulation released [3H]NE. Caffeine had no effect on the release. When [Ca2+]i was measured in growth cones, only electrical stimulation produced an increase in [Ca2+]i. The other agents had no effect on Ca2+ at the terminal regions of the neurons. We conclude that Ins(1,4,5)P3-insensitive, but caffeine-sensitive Ca2+ stores in sympathetic neurons are located only in the cell body and are not coupled to [3H]NE release. PMID- 2213026 TI - Corticosterone regulates the expression of ADP-ribosylation factor messenger RNA and protein in rat cerebral cortex. AB - ADP-ribosylation factors (ARFs) comprise a family of small GTP-binding proteins found in brain and other tissues. Recent studies have demonstrated that the expression of the larger heterotrimeric guanine nucleotide binding proteins is under control by steroid hormones. Therefore, in the present study, we examined the influence of glucocorticoids on the expression of ARF mRNA and protein. using specific cDNA probes and antisera, respectively. Chronic administration of corticosterone (7 days) significantly increased levels of mRNA for ARF1 and ARF3, two subtypes of ARF, in rat cerebral cortex. Chronic administration of corticosterone was also found to increase levels of ARF immunoreactivity in this brain region. However, 1-day administration of corticosterone did not influence levels of mRNA for either ARF1 or ARF3. In contrast to corticosterone, bilateral adrenalectomy (7 days after surgery) was found to decrease ARF1 and ARF3 message relative to sham controls; this effect of adrenalectomy was reversed by corticosterone treatment. These results demonstrate that the expression of ARF is under hormonal control and may underlie aspects of glucocorticoid action on neuronal function. PMID- 2213027 TI - Early changes in nuclear proteins following axotomy. AB - Changes in protein synthesis are thought to be important in the response of the neuron to axotomy. Certain axonally transported proteins whose synthesis increases probably play important roles in regeneration of the axon. Although little is known about the regulation of these changes, the cell often controls its production of proteins at the nuclear level, where transactivating proteins modulate the transcription of specific genes. Thus, changes in nuclear proteins might be expected to be among the early events following axotomy, but such changes have not yet been described. We have addressed this issue by dissecting out single nuclei from [35S]methionine-labeled giant R2 neurons of Aplysia and analyzing the proteins by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This procedure was used to avoid contamination with nonneuronal and nonnuclear proteins. Our results demonstrate large increases in two nuclear proteins (56 kDa and 41 kDa) and decreases in two others (77 kDa and 46 kDa) 5 h after axotomy. These are the earliest postaxotomy changes in [35S]methionine-labeled proteins that have been reported. PMID- 2213028 TI - Two new steroidal alkaloids from Fritillaria ussuriensis. PMID- 2213029 TI - New polyhydroxylated triterpenes from Uncaria tomentosa. AB - Three novel polyhydroxylated triterpenes have been isolated from Uncaria tomentosa. Their structures were established as 1, 2, and 3 by detailed spectral studies including 1H-13C correlations via long range couplings using the INAPT pulse sequence, nOeds, and 2D 1H-13C direct chemical shift correlation (HETCOR) nmr techniques. PMID- 2213031 TI - New hydroxylated benzo[c]phenanthridine alkaloids from Eschscholtzia californica cell suspension cultures. AB - From cell cultures of Eschscholtzia californica and their spent medium, three new benzo[c]phenanthridine alkaloids--namely 10-hydroxysanguinarine [2a], 12 hydroxychelirubine [4a], and 10-hydroxychelerythrine [7a]--and two new dihydrobenzo[c]phenanthridine alkaloids--10-hydroxydihydrosanguinarine [2b] and 12-hydroxydihydrochelirubine [4b]--together with the known constituents sanguinarine [1a], chelirubine [3a], macarpine [5a], dihydrosanguinarine [1b], dihydrochelirubine [3b], and dihydromacarpine [5b], were isolated and characterized. Structure elucidations were done by 1H nmr, decoupling experiments, and NOESY spectra. Isolated microsomes from E. californica, the site of hydroxylation activity within the cells, contained the whole set 1b to 8b of 5,6-dihydrobenzo[c]phenanthridines. A scheme for the biosynthesis of macarpine [5a] from protopine [9] via dihydrosanguinarine [1b] is presented. PMID- 2213030 TI - Guaianolides and eudesmanolides from Centaurea ornata. AB - Four sesquiterpene lactones and three other compounds have been isolated from the EtOH-H2O-soluble fraction of a CHCl3 extract of Centaurea ornata. A new grosshemin derivative 3 is described, and the stereochemistry of natural 11-epi dihydroreynosin [2] is revised. PMID- 2213033 TI - Potential inhibitors of platelet aggregation from plant sources, V. Anthraquinones from seeds of Cassia obtusifolia and related compounds. AB - Three anthraquinone glycosides, gluco-obtusifolin [11], gluco-chryso-obtusin [15], and gluco-aurantioobtusin [13], were found to be platelet anti-aggregatory constituents of seeds of Cassia obtusifolia. Various other anthraquinone analogues were also tested, and their structure-activity relationships are discussed. PMID- 2213032 TI - 7-deoxy-6-epi-castanospermine, a trihydroxyindolizidine alkaloid glycosidase inhibitor from Castanospermum australe. AB - A new indolizidine alkaloid has been isolated from the seeds of Castanospermum [1] australe and identified as 7-deoxy-6-epi-castanospermine by ms and 1H- and 13C-nmr spectroscopy. The alkaloid is the first trihydroxylated indolizidine to be isolated from this plant and may represent an intermediate in the biosynthetic pathway to the tetrahydroxy-indolizidines and -pyrrolizidines. It inhibits amyloglucosidase and yeast alpha-glucosidase but is significantly less active as a glycosidase inhibitor than its isomer swainsonine [2] and the tetrahydroxylated alkaloids castanospermine [3], 6-epi-castanospermine [4], and australine [5]. PMID- 2213034 TI - Microbiological transformation of (+/-)-flavanone and (+/-)-isoflavanone. AB - The microbiological transformation of flavanone and isoflavanone was explored using a group of 80 microorganisms in the initial screening. Ten metabolites of flavanone were isolated and identified as 4'-hydroxyflavanone [3], 3',4' dihydroxyflavanone [4], 3-hydroxyflavone [2], flavone [5], 2' hydroxydihydrochalcone [7], 2',4-dihydroxydihydrochalcone [6], 2',3,4 trihydroxydihydrochalcone [8], 2',5'-dihydroxydihydrochalcone [9], 4' hydroxyflavan-4 alpha-ol [11], and 2'-hydroxydibenzoylmethane [10]. The isoflavanone metabolites were identified as isoflavone [15], 2 hydroxyisoflavanone [16], 4'-hydroxyisoflavanone [13], 6,4'-dihydroxyisoflavanone [17], and 3',4'-dihydroxyisoflavone [14]. The structures of the metabolites were established using spectroscopic techniques including ir, ms, uv, 1H-nmr, and 13C nmr spectroscopy. Production of 4'-hydroxyflavanone, 3',4'-dihydroxyflavanone, and 2',4-dihydroxydihydrochalcone by 13 microorganisms was assayed using reversed phase hplc. PMID- 2213035 TI - ent-kauranoid diterpenes from Artemisia sacrorum. AB - A new ent-kauranoid diterpene diglycoside has been isolated from Artemisia sacrorum along with two known ent-kauranoid diterpenes. Their structures are elucidated by means of nmr analysis (DEPT, 1H-1H COSY, 1H-13C COSY, and 1H-1H decoupling). PMID- 2213037 TI - Synthesis of [ring B-13C6] diosmin. AB - End products of flavone metabolism are phenolic acids, originating from rings B and C2 and/or C3 of ring C. Several of them are also endogenous products. Synthesis of uniformly labeled ring B-13C-diosmin [5] was performed for the unambiguous distinction, by ms, between endogenous and exogenous phenolic acids. PMID- 2213036 TI - Effect of magnesium lithospermate B on urinary prostaglandins in rats with renal failure. AB - Urinary excretion of prostaglandin E2 showed a significant increase following administration of magnesium lithospermate B [1] in rats with renal failure. In contrast, that of thromboxane B2 showed a significant decrease, indicating the improvement of renal failure. PMID- 2213038 TI - The widening spectrum of infectious neurological disease. PMID- 2213039 TI - Botulinum toxin treatment of cranial-cervical dystonia, spasmodic dysphonia, other focal dystonias and hemifacial spasm. AB - In the past five years, 477 patients with various focal dystonias and hemifacial spasm received 3,806 injections of botulinum A toxin for relief of involuntary spasms. A definite improvement with a global rating greater than or equal to 2 on a 0-4 scale, was obtained in all 13 patients with spasmodic dysphonia, 94% of 70 patients with blepharospasm, 92% of 13 patients with hemifacial spasm, 90% of 195 patients with cervical dystonia, 77% of 22 patients with hand dystonia, 73% of 45 patients with oromandibular dystonia, and in 90% of 21 patients with other focal dystonia who had adequate follow up. While the average duration of maximum improvement lasted about 11 weeks after an injection (range seven weeks in patients with hand dystonia to 15 weeks in patients with hemifacial spasm), some patients benefited for over a year. Only 16% of the 941 treatment visits with follow up were not successful. Except for transient focal weakness, there were very few complications or systemic effects attributed to the injections. This study supports the conclusion that botulinum toxin injections are a safe and effective therapy for patients with focal dystonia and hemifacial spasm. PMID- 2213040 TI - Botulinum toxin treatment in spasmodic torticollis. AB - Botulinum toxin A was administered to 19 patients in a double-blind placebo controlled trial. Toxin was more effective than placebo for improving both head position and pain which was measured by an objective rating scale and videofilm assessments. Following the controlled trial, treatment with botulinum toxin was continued in an open fashion. A total of 60 patients with torticollis received toxin in a total of 117 treatment periods. The mean follow up period was 8.4 months. In 39 patients with pain there was benefit in 77% of treatment periods. Some improvement in neck posture occurred in 83% of the treatment periods with a mean duration of 12 weeks. Side effects were frequent with dysphagia being the most common (28% of treatment periods). Botulinum toxin is an effective treatment for toticollis but treatment should be initiated with doses at the lower end of the range used in this study (400-600 mouse units). PMID- 2213041 TI - Central nervous system haemangioblastoma: a clinical and genetic study of 52 cases. AB - Fifty two cases of haemangioblastoma were reviewed for their clinical, genetic and prognostic features. Of 34 patients with apparently isolated cerebellar lesions, postoperative outcome was good in 79%. Six isolated spinal lesions presented more insidiously and morbidity was related to incomplete resection. Twelve (23%) of the patients definitely had von Hippel-Lindau disease (VHLD). The true proportion may be higher as this diagnosis was not definitely excluded in many of the remainder; only ten patients with seemingly isolated cerebellar tumours were appropriately investigated and two had evidence of VHLD. Four out of 26 cases (15%) with apparently completely resected, isolated, cerebellar lesions later developed recurrent tumours. Brainstem and supratentorial haemangioblastomas were rare and were always associated with VHLD. The cerebellar or spinal haemangioblastomas due to VHLD had no distinctive clinical features compared with isolated tumours and there was considerable overlap in age of onset between the two groups of cases. All patients with an apparently isolated CNS haemangioblastoma should be investigated for evidence of von Hippel-Lindau disease. PMID- 2213042 TI - The relationship of antibody levels to the clinical spectrum of human neurocysticercosis. AB - One hundred proven cases of cerebral cysticercosis were studied with an enzyme linked immunoassay (ELISA) employing cyst fluid as antigen, with a view to detecting specific antibodies in serum and cerebrospinal fluid (CSF). Antibody levels were correlated with the clinical presentation of the patients, the type and number of cysts detected on their brain scans, the anatomical position of these cysts and the presence of lymphocytes in the CSF. Patients could be divided into two distinct categories, one with low levels of antibody in the serum and absent antibody in the CSF, and the other with high levels in both the serum and the CSF. This differentiation matched the clinical presentation of a benign and a malignant group. Antibody levels could not be related to the type of cysts as observed on the brain scan, but depended on the anatomical position of the cyst, being lower if the cysts were confined to the cerebral cortex. A correlation of antibody levels with the number of cysts was only found in the benign group. PMID- 2213043 TI - Clinical and genetic heterogeneity in early onset cerebellar ataxia with retained tendon reflexes. AB - A clinical and genetic study was performed on 20 patients affected by early onset cerebellar ataxia with retained tendon reflexes (EOCA). Mean age at onset was 8.8 (SD 6.0) years. The frequency distribution of age of onset significantly differed from the normal distribution. Consanguinity rate was 16.7% and segregation ratio 0.164. As well as ataxia, which was a constant feature, there were signs of involvement of the cortico-spinal tracts and/or peripheral nerves in most patients. Results of neurophysiological studies were not homogeneous, nor were morphological findings of the sural nerve biopsy. The data suggest that EOCA may be genetically and clinically heterogeneous. PMID- 2213044 TI - Hemiparetic multiple sclerosis. AB - Eight patients are described who presented with hemiparesis which involved the face in seven. Six of the eight subsequently developed clinically definite multiple sclerosis and in the remaining two patients multiple sclerosis was the likely diagnosis. Magnetic resonance imaging gave useful information about the site of the lesions responsible for the presenting syndrome and provided additional information in support of a diagnosis of multiple sclerosis. PMID- 2213045 TI - Extradural implantation of sacral anterior root stimulators. AB - A technique for extradural deafferentation of the S2 to S5 segments and extradural implantation of stimulating electrodes is described, and its application to twelve patients with spinal cord lesions is reported. Nine patients use their implants for micturition, and seven are fully continent. The advantages and disadvantages of this technique compared with the more usual intrathecal procedure are discussed. PMID- 2213046 TI - Bimanual simultaneous motor performance and impaired ability to shift attention in Parkinson's disease. AB - The ability to share time and to shift attention between bimanual simultaneous motor tasks were studied in 18 patients with Parkinson's disease (PD) and 19 age- and intelligence-matched controls. The task consisted of drawing triangles with the dominant hand and squeezing a rubber bulb with the nondominant hand. Motor performance was measured using the variables: amplitude of squeezing, frequency of squeezing and velocity of drawing triangles. After eliminating variance due to baseline differences in single-handed performance, the bimanual simultaneous performance of PD and controls turned out to be similar to the frequency of squeezing and the velocity of drawing triangles. The amplitude of squeezing, however, differed between the two groups: it was significantly reduced in PD. Arguably the disturbance in the bimanual performance of PD patients was not due to a disorder of time sharing, but to a decreased ability to shift attention from the visually cued task to the non visually cued task. The results agree with current evidence that PD patients are more impaired when they have to rely upon internal control for the regulation of shifting attention than when external cues are available. PMID- 2213047 TI - The treatment of Gilles de la Tourette syndrome by limbic leucotomy. AB - A patient with Gilles de la Tourette syndrome and severe self-injurious compulsions who had failed to respond to drug treatment and behavioural therapy obtained a complete and sustained resolution of his destructive behaviour and improvement in his tics following bilateral limbic leucotomy. PMID- 2213048 TI - LDH isoenzymes in cerebrospinal fluid in various brain tumours. AB - This study examined the isoenzymatic pattern of LDH in the cerebrospinal fluid (CSF) as well as the ratio between the five fractions of LDH among patients with various brain tumours, carcinomatous meningitis and control groups. LDH 1/LDH 2 less than 1 was found significant for carcinomatous meningitis (p less than 0.001) and brain metastases (p less than 0.001). LDH 1/LDH 2 ratio was found to be significantly lower in carcinomatous meningitis than in brain metastases (p less than 0.05). No LDH 1/LDH 2 ratios smaller than 1 were found in the other groups. The LDH 1/LDH 2 ratio smaller than 1 was found in the early stage of carcinomatous meningitis without other evidences of the involvement of the leptomeninges. Examination of LDH 1/LDH 2 can be found as an adjunctive method to identify brain metastases and carcinomatous meningitis at the initial stage. PMID- 2213049 TI - Practice effects on the preprogramming of discrete movements in Parkinson's disease. AB - The effects of practice on the simple and choice reaction times (RTs) of Parkinson's disease (PD) and control subjects in a discrete aiming task were analysed. For controls, practice led to a selective decrease in choice RTs, as has been reported previously. An opposite effect was seen in the PD group, with little change in choice RTs and substantial reduction in simple RTs. The results suggest that PD subjects can use advance information to initiate discrete movements more rapidly, but that this ability to "preprogramme" movements requires practice. Reconciliation of these results with studies reporting an inability to preprogramme in PD are made in a discussion of task characteristics which may allow or preclude preprogramming. PMID- 2213051 TI - Occupational meralgia paraesthetica. PMID- 2213050 TI - Transcranial magnetic stimulation can influence the selection of motor programmes. AB - Transcranial magnetic stimulation is becoming increasingly popular to study the rapidly conducting output from the motor cortex. Little is known about the effects of such stimuli on other aspects of cortical function. In the study single magnetic stimuli, subthreshold for movement, produced significant preference for selection of one hand in a forced-choice task. The hand preference depended upon the direction of the induced current. It occurred when the coil was positioned over frontal but not occipital cortex and was not mimicked by weak DC stimulation. Single magnetic stimuli which do not evoke movement can alter high level motor planning. PMID- 2213052 TI - Vertical gaze palsy due to a resolving midbrain lesion. PMID- 2213053 TI - Mumps and Guillain-Barre syndrome. PMID- 2213054 TI - The role of combined valve prolapses in the prognosis of cerebro-vascular ischaemic attacks associated with mitral valve prolapse. PMID- 2213055 TI - Combined neuroleptic malignant syndrome and the central anticholinergic syndrome. PMID- 2213056 TI - Intraoperative aneurysms rupture during the predissection stage. PMID- 2213057 TI - Proceedings of the Association of British Neurologists. London, 27-29 October 1988. Abstracts. PMID- 2213058 TI - Intrathecal baclofen for treatment of spasticity. PMID- 2213059 TI - Modeling of protease I collagenolytic enzyme from the fiddler crab Uca pugilator. AB - Collagenolytic protease I from the fiddler crab Uca pugilator belongs to the serine proteases of the trypsin family. A graphic molecular model was built using information from sequences and X-ray structures of four homologous proteins which were superimposed to define structurally conserved regions. Protease I sequence was aligned, with sequences of the model proteins, without permitting any deletion or insertion in these regions. Elastase alpha-carbon chain was selected as a template molecule. For the structurally variable regions, fragments of the four homologous proteins which were 'closet' in sequence were selected. Intramolecular steric hindrance, that resulted from the substitution of the residues of the templates by protease I residues, was corrected by adjustment of the side-chain conformational angles. The model was then optimized by energy minimization. The primary specificity pocket in the model of collagenolytic protease I predict a substrate preference for both P1 hydrophobic and positively charged residues which is in agreement with the biochemical observations. As soybean trypsin inhibitor (STI) is known to inhibit collagenolytic protease I, a tentative model of the complex was constructed and possibilities of interaction examined. PMID- 2213060 TI - Computer Automated Structure Evaluation (CASE) of the teratogenicity of retinoids with the aid of a novel geometry index. AB - The CASE (Computer Automated Structure Evaluation) program, with the aid of a geometry index for discriminating cis and trans isomers, has been used to study a set of retinoids tested for teratogenicity in hamsters. CASE identified 8 fragments, the most important representing the non-polar terminus of a retinoid with an additional ring system which introduces some rigidity in the side chain. The geometry index helped to identify relevant fragments with an all-trans configuration and to distinguish them from irrelevant fragments with other configurations. PMID- 2213061 TI - CGEMA and VGAP: a Colour Graphics Editor for Multiple Alignment using a variable GAP penalty. Application to the muscarinic acetylcholine receptor. AB - Today, more than 40 protein amino acid (AA) sequences of membrane receptors coupled to guanine nucleotide binding proteins (G-proteins) are available. For those working in the field of medicinal chemistry, these sequences present a new type of information that should be taken into consideration. To make maximal use of sequence data it is essential to be able to compare different protein sequences in a similar way to that used for small molecules. A prerequisite, however, is the availability of a processing environment that enables one to handle sequences in an easy way, both by hand and by computer. In order to meet these ends, the package CGEMA (Colour Graphics Editor for Multiple Alignment) was developed in our laboratory. The programme uses a user-definable colour coding for the different AAs. Sequences can be aligned by hand or by computer, using VGAP, and both approaches can be combined. VGAP is a novel in-house written alignment programme with a variable gap penalty that also handles consecutive alignments using one sequence as a probe. In addition, secondary structure prediction tools are available. From the 20 protein sequences, available for the muscarinic acetylcholine receptor, 13 different sequences were selected, covering the subtypes m1 to m5. By comparing the sequences, two major groups are revealed that correspond to those found by considering the transducing system coupled to the various receptor subtypes. Different parts of the protein sequences are identified as characterizing the subtype and binding the ligands, respectively. PMID- 2213062 TI - A semiempirical SCF-MO study of the tautomeric forms of 3-acetyl tetronic- and tetramic acids. AB - A number of tautomeric geometries of 3-acetyl tetramic acid and 3-acetyl tetronic acid were examined using the AM1 and PM3 methods. The results are compared with experimental data and with studies using MNDO and older methods, with the conclusion that both AM1 and PM3 provide satisfactory models of the behaviour of these species. PMID- 2213063 TI - Automatic log P estimation based on combined additive modeling methods. AB - A program for the automatic estimation of the logarithm of the partition coefficient between 1-octanol and water phases (log P) has been developed as a component of a system entitled CHEMICALC (Combined Handling of Estimation Methods Intended for Completely Automated Log P Calculation). Log P values are calculated based on additive group contributions to log P. Three sets of groups are defined, and their contributions have been derived from the experimental log P values of 1465 molecules. The system divides a structural formula of a compound of interest into the groups whose increments are provided and then calculates its log P value. All processing after structure input is fully automated. This system has been tested for predicting the log P values of 1686 compounds. The accuracy is sufficient for many practical purposes. PMID- 2213066 TI - Cholesterol: consensus and controversy. PMID- 2213064 TI - Solvation of the active site of cytochrome P450-cam. AB - Energetically favorable water binding sites in the substrate pocket of cytochrome P450-cam have been predicted by a molecular mechanics method. Binding sites corresponding to all the experimentally observed water sites in this region of the enzyme were located. The calculations also indicate the presence of two further water binding sites. One of these is located in a hydrophobic region of the protein where a water molecule would not bind tightly to the substrate-free enzyme. However, in the substrate-bound enzyme, a water molecule in this region could donate a hydrogen bond of optimum geometry to the carbonyl oxygen atom of the camphor substrate and could therefore contribute to the correct positioning of the camphor substrate for 5-exo-hydroxylation. These calculations also suggest that a steric analogue of camphor, containing an alkyl group which could prevent a water molecule from binding in this region, might inhibit cytochrome P450-cam by forming a more stable enzyme-ligand complex than camphor itself. PMID- 2213065 TI - Automated site-directed drug design: approaches to the formation of 3D molecular graphs. PMID- 2213067 TI - Cholesterol policy: what should we do? How should we decide? PMID- 2213068 TI - Intimations of uncertainty in the practice of medicine. PMID- 2213069 TI - Fitness and risk factors for coronary disease. PMID- 2213070 TI - File drawers, p values and efficacy of drugs. PMID- 2213072 TI - "Would" vs "should" in the definition of secondary study base. PMID- 2213071 TI - Drug banning and the regulatory process. PMID- 2213073 TI - Are drug benefits also part of pharmacoepidemiology? PMID- 2213074 TI - The use of risk factors in medical diagnosis: opportunities and cautions. AB - We discuss in this paper the extent to which disease risk factors may assist in the diagnostic process. We caution that disease risk factors need not be very sensitive or specific. Risk factor specificity and sensitivity may be further reduced if, in the former case, the risk factor is related to other illnesses having the same clinical presentation as the disease of interest, or if, in the latter case, the risk factor disappears with the onset of illness. We illustrate these points in a discussion of the utility of smoking as a diagnostic test for malignancy in two clinical situations, the patient with asymptomatic microscopic hematuria and the patient with a solitary pulmonary nodule. Risk factors hold great promise as aids to medical diagnosis, as this information is readily available to clinicians at little or no cost. Clinicians, however, should exercise caution when using risk factors of unproven diagnostic utility in medical diagnosis, as their presence may have little or no effect on disease probability. PMID- 2213075 TI - Blood pressure reactivity predicts myocardial infarction among treated hypertensive patients. AB - High blood pressure (BP) defines a prognostically heterogeneous group. Because BP varies according to time, setting and means of observation, it has been postulated that BP reactivity might better predict cardiovascular disease (CVD) than does unidimensional measurements. To assess BP reactivity, the difference between pretreatment nurse (RN) and physician (MD) diastolic BP (DBP)- systematically recorded in that order--or MD-RN DBP, was obtained in 1737 previously untreated patients with sustained, RN BP greater than or equal to 160 and/or 95 mmHg. Patients stratified by tertiles of MD-RN DBP [(I) less than or equal to - 3, (II) -2 to 3 and (III) greater than or equal to 4 mmHg] were similar by sex, race, age, body mass index, cholesterol, electrocardiography, prior CVD, smoking and pretreatment or attained in-treatment BPs. During 14 years of followup, myocardial infarction (MI) incidence per 1000/year were, tertile I (3.2), II (3.7), III (7.6) (relative risk = 2.4, III vs I + II, p less than 0.05), whereas stroke incidence and non-CVD mortality were evenly distributed. By Cox survival analysis, controlling for other entry characteristics only age, sex and DBP reactivity remained predictive (p less than or equal to 0.03) of MI or total CVD. Thus, BP reactivity, probably a centrally-mediated phenomenon, identifies a subgroup of hypertensives with an increased propensity for MI despite successful BP control. PMID- 2213076 TI - Spirometric findings and mortality in never-smokers. AB - The relation of ventilatory function to overall mortality has been studied in 662 male and 2048 female never-smokers who during the period 1976-1978 participated in the Copenhagen City Heart Study, a prospective community study of more than 14,000 men and women randomly selected from the general population of the City of Copenhagen. Until the end of 1986, 195 subjects who said they were never-smokers died. Mortality was analyzed using the proportional hazards model of Cox. In addition to measures of ventilatory function, the mortality analysis included age, sex, body-mass index, alcohol consumption, school education, diabetes mellitus, heart disease and bronchial asthma as confounding factors. Forced expiratory volume in 1 second (FEV1) as a percentage of that predicted, forced vital capacity (FVC) as a percentage of that predicted and the ratio of FEV1 to FVC were significant risk factors for mortality among both sexes. The relative risk of death associated with a 50% decrease in FEV1 and FVC as a percentage of a predicted value was 1.65 and 1.81, respectively. This study confirms that lowered ventilatory function is a strong risk factor for mortality among never-smokers of both sexes. PMID- 2213077 TI - Estimating the benefits of cholesterol lowering: are risk factors for coronary heart disease multiplicative? AB - It is often stated that the major risk factors for coronary heart disease (CHD)- smoking, high blood pressure and high serum cholesterol--are not merely additive but act together such that each multiplies the effects of the others. Economic analyses in which the benefits of risk factor modification are estimated often reflect this. This paper explains how predictive models based on the simplest form of the multiple logistic function inevitably predict greater benefit from cholesterol lowering in those in whom other risk factors are adverse; this results from the model itself, rather than the data. CHD death rates from the screenee population of the Multiple Risk Factor Intervention Trial are examined: these suggest that the relationship between cholesterol and both other major risk factors is closer to additive than to multiplicative. When the benefits of cholesterol lowering are estimated, a model based on additive risk, specifying product ("interaction") terms, is to be preferred. PMID- 2213078 TI - Hospitalization experience of Navajo subjects with type II diabetes and matched controls: an historical cohort study. AB - Using an historical cohort study design with a 12 year follow-up, we found that 77 Navajo adults with type II diabetes mellitus were hospitalized at a rate of 335 hospitalizations per 1000 patient years compared to a rate of 167 hospitalizations per 1000 patient years for 77 age, sex, and residence matched non-diabetic controls, yielding a risk ratio of 2.0. Using matched pairs analysis (sign test), the observed difference in number of hospital admissions is statistically significant (z = 2.30, p less than 0.05). The average duration of hospitalization, however, was not statistically different in matched pairs analysis (z = 0.95, p greater than 0.05). The 136 excess hospitalizations of the diabetic subjects included 45 admissions for poor metabolic control of diabetes, 50 excess admissions for infectious disease, and 26 excess admissions for conditions of the heart, eye, kidney, or non-traumatic amputation. In multivariate analyses, variables found to be associated with greater hospitalization experience among the 77 diabetic subjects in the 12 years follow up period included older age at entry to the study, poorer metabolic control early in the study period, and presence of diabetic complications. PMID- 2213079 TI - The leukocyte count: a predictor of hypertension. AB - In an exploratory study of 1031 persons observed to progress from normotension to essential hypertension and 1031 matched subjects who remained normotensive, the initial leukocyte count (WBC) was found to be related to the development of hypertension, with risk increased 40% (95% confidence interval 12-82%) in persons in the highest as compared to the lowest quartile of WBC. This relationship proved to be largely independent of body mass index, body fat distribution, alcohol and tobacco consumption, and parental history of hypertension. An increased WBC may reflect greater sympathetic tone or may directly increase peripheral vascular resistance by impeding circulation through small blood vessels. If confirmed, this study adds another condition to the growing list for which the WBC is predictive. This simple, cheap test should be considered for inclusion in prospective epidemiological studies of many different diseases. PMID- 2213080 TI - Plasma fibrinogen and coronary risk factors: the Scottish Heart Health Study. AB - Plasma fibrinogen was measured in a sample of 8824 men and women aged 40-59 years participating in the Scottish Heart Health Study, and related to cardiovascular risk factors. Women had higher fibrinogen levels than men. In both sexes, multivariate analysis showed that fibrinogen was positively associated with age, smoking, total cholesterol and body mass index and negatively associated with alcohol consumption. Among women, early menopause and systolic blood pressure were also associated with fibrinogen levels. Univariate analyses showed weak positive associations with fish consumption for both sexes although only male white fish consumption entered the final model. Women with a history of contraceptive pill usage had significantly lower fibrinogen levels. The relationship between fibrinogen and physical activity was complex, and could largely be explained by smoking. These findings support the hypothesis that raised fibrinogen is one mechanism by which several major risk factors may promote coronary heart disease. However, known risk factors explained, at most, 10% of the total variance in fibrinogen levels among the general population. PMID- 2213081 TI - The effects of generation and gender on the joint distributions of lipid and apolipoprotein phenotypes in the population at large. AB - The generation and gender effects on the joint distributions of total plasma cholesterol (Total-C), ln triglycerides (lnTrig), HDL-cholesterol (HDL-C), LDL cholesterol (LDL-C), apolipoproteins AI (Apo AI), AII (Apo AII), and E (lnApo E) were studied in 184 male grandparents (MGP), 242 female grandparents (FGP), 237 male parents (MP), 235 female parents (FP), 202 male children (MC), and 200 female children (FC). Homogeneity of variance tests revealed that lipid variances were gender and/or generation specific while apolipoprotein variances were homogeneous across strata. In the absence of heterogeneity of variance, significant heterogeneity in LDL:lnTrig and lnTrig:Apo AII covariation was found between genders in the parental generation. In the presence of heterogeneity of variance, significant heterogeneity of correlation between genders and/or across generations was found for the HDL-C:LDL-C, Total-C:LDL-C, Total-C:lnTrig, lnTrig:LDL-C, Total-C:lnApo E and HDL-C:lnApo E bivariate distributions. Analyses of principal components revealed that the generation and gender specific cohorts have similar eigenvalues but distinct eigenvectors for the first two principal components underlying the seven dimensional lipid and apolipoprotein distribution. We conclude that the amount of variability explained by the first two principal components is the same across cohorts but how the interindividual variability is distributed among the lipid and apolipoprotein traits is generation and gender specific. This study documents the role that variance and covariance might play in determining risk of disease for special subgroups of the population at large. It also demonstrates how variances and covariances between risk factors traits characterize life processes of aging and sexual dimorphism. This study argues that future biometrical genetic and epidemiological studies of coronary artery disease must take into account age and gender effects on interindividual variability and covariability of risk factors. PMID- 2213082 TI - Validation study methods for estimating exposure proportions and odds ratios with misclassified data. AB - Two methods for making adjustments to an estimate of exposure when data are possibly misclassified are discussed. One, the indirect method, is widely used but the other, the direct method, seems less well-known, despite it being a rather more obvious approach. To implement either requires some knowledge of misclassification rates and it may be possible to estimate these by a validation study. Depending on how sampling for such a study is done, one has the choice of what method to use. Formulae for the variance of estimates are derived and the precision of the methods compared. The direct approach is found to be more efficient. PMID- 2213083 TI - Body mass index and 15-year mortality in a cohort of black men and women. AB - The association between body mass index (BMI) and mortality was investigated in 2453 black male (aged 30-79 years) and 2731 black female (aged 40-79 years) members of the Kaiser Foundation Health Plan. During a 15-year follow-up 393 male and 283 female deaths were identified. Analyses were conducted separately in a lower and an upper range of BMI (as well as over the entire range), to isolate separate effects of low weight and high weight on mortality. Particular attention was also paid to potential bias from cigarette smoking and antecedent illness. Cox regression analyses showed that over the entire range of BMI the adjusted BMI mortality association was significantly J-shaped for the men and essentially flat for the women. The inverse association between BMI and mortality in the lower range of BMI was statistically significant for the men; the adjusted relative hazard increasing from the 10th to the 50th percentile of BMI was 0.76 (95% confidence interval [CI] 0.59-0.98). The positive association between BMI and mortality in the upper range of BMI was highly statistically significant for the men; the adjusted relative hazard increasing from the 50th to the 90th percentile of BMI was 1.37 (95% CI 1.14-1.63). Whether controlled by multivariate analysis, by excluding the first 5 years of follow-up from the analyses, or by analyzing the BMI-mortality association in smoking-specific and/or illness-specific subgroups, smoking and antecedent illness did not have much impact on the BMI mortality association, in either sex. The general observations on the BMI mortality association are similar to findings in some white cohorts. PMID- 2213084 TI - Risk ratios and risk differences in estimating the effect of risk factors for cardiovascular disease in the elderly. AB - This article reviews the nature of the effects of hypertension, smoking and cholesterol on the incidence of cardiovascular disease and emphasizes how these effects vary by age. In the Methods section, we discuss briefly the concepts of additive and multiplicative statistical models as tools for summarizing data. In the results section, we summarize available data on the association between incident stroke and coronary heart disease in the elderly and each of these major risk factors. The traditional multiplicative model parsimoniously characterizes the individual and joint effects of age and high blood pressure in terms of risk ratios; but, for smoking and cholesterol, an additive model appears to be the most parsimonious. We discuss the consequences of these observations for the study and prevention of cardiovascular disease in the elderly. PMID- 2213085 TI - Changes in surgical treatments: the example of hysterectomy versus conization for cervical carcinoma in situ. AB - From 1969 through 1985, 4584 women in the state of New Mexico were diagnosed with carcinoma in situ of the cervix. Of these women, 65.5% underwent hysterectomy while 31.1% had a conservative therapy (primarily conization). Over the 17-year period, there was a steady increase in the percentage of women receiving conservative therapies, from 11.8% in 1969 to 50.3% in 1985. Younger women, unmarried women and American Indian women were more likely to receive conservative therapy. This marked shift in therapeutic approach occurred during a time of apparent controversy as to the optimal treatment for cervical carcinoma in situ, and illustrates a rapid change in surgical practice in the absence of any controlled trials comparing the two major treatment modalities. PMID- 2213087 TI - Shortening the State-Trait Anxiety Inventory. AB - Questionnaires that are used in studies with severely patients should be as short as possible. Abridged versions of existing inventories are very practical in these instances. The answers of 444 subjects in three samples (cancer patients, medical students, surgical patients) were used to investigate the possibility of constructing short and reliable versions of the scales of the State and Trait Anxiety Inventory. A stepwise regression procedure showed the possibility to reliably predict the total score of the unabridged versions by means of weighted sums of eight items for each scale. Omission of weights did not lead to substantial loss of information. Cronbach's alpha of the State-scale decreased from 0.93 to about 0.85 for different combinations of items and from 0.91 to about 0.82 for combinations of eight items of the Trait-scale. The relationship between both scales was only slightly modified by the shortening procedure. PMID- 2213086 TI - The relationship of headache symptoms with severity and duration of attacks. AB - Efforts to develop clinically useful headache classification schemes have generally focused on linking specific symptom groupings with specific headache subtypes. An alternative conceptual approach, the "severity model" of headache, considers a continuum of headache ranging from mild to severe forms with specific headache subtypes distinguished by level of severity rather than unique constellations of symptoms. A population-based telephone interview was carried out among 10,169 subjects aged 12-29 to estimate the prevalence of serious headaches and better characterize symptoms that accompany headache attacks. In an analysis of frequency of occurrence, pain and duration of recent (within 4 weeks prior to interview) headache attacks, the data revealed that common symptoms (such as forehead pain and pain in the back of the head, neck and shoulders) were reported frequently, but headaches with these symptoms were generally characterized by low levels of pain and short duration. Although not an original study objective, the data were analyzed to determine whether distinct symptom constellations could be identified or whether symptoms overlapped between headache types. Symptoms of migraine were frequently experienced concomitant with tension-type symptoms; the resultant headaches were usually characterized as moderate in intensity. In contrast, symptoms usually associated with migraine in the absence of concomitant tension-type symptoms were infrequently experienced, but resulted in headaches causing the greatest disability. The data provide some support for the severity model of headache. PMID- 2213088 TI - Coping with heart disease. PMID- 2213089 TI - Assessing the coping status of spouses of critically ill cardiac patients: a theoretically based approach. AB - Acute cardiovascular disease is an emotionally traumatic event for the patient and family alike. As nurses are concerned with optimizing the health and well being of patients and families, the nurse's role in assessing coping responses of the spouses is critical for the formulation of appropriate nursing diagnoses and the development of effective interventions. This article describes the spousal coping instrument, which is based on a conceptual model of nursing and is designed to comprehensively assess the coping responses, factors that influence coping, and outcomes of spouses whose partners have suffered an acute cardiac event. PMID- 2213090 TI - Psychosocial adjustment to coronary artery disease: current knowledge and future directions. AB - Adjusting to the diagnosis of coronary artery disease can be a challenge to the coping abilities of patients and their families. To effectively support these clients' coping efforts, cardiovascular nurses must be knowledgeable about factors that affect the adjustment process. This article reviews recent findings regarding physiologic, psychologic, and sociodemographic influences on adjustment and presents a model that integrates these findings. Possible directions for further research are suggested. PMID- 2213091 TI - Coping and adjustment to illness in the acute myocardial infarction patient. AB - This study examined the coping strategies of acute myocardial infarction (MI) patients one month following discharge from the hospital. Problem- and emotion focused coping strategies were identified in 30 acute MI patients and correlated with psychologic, social, and physiologic adjustment variables. Individuals who used more problem-focused coping than emotion-focused coping were found to have better social (p less than .005) and psychologic adjustment (p less than .05). Individuals who had more physiologic symptoms were found to have poorer psychologic adjustment. Early identification of those patients at risk for psychosocial distress is paramount to maximize the patient's coping process and prepare the patient psychologically prior to hospital discharge. PMID- 2213092 TI - Nursing interventions for families of cardiac surgery patients. AB - Caring for the cardiac surgery patient includes intervening with the patient's family members. It is important for the nurse to acquire the knowledge base to implement appropriate interventions with family members. An intervention program was designed to meet the needs of family members of cardiac surgery patients based on a compilation of previous research data. This program included providing educational classes for the nursing staff as well as giving written information and support to the family member while visiting in the intensive care unit. A visiting intervention checklist was given to each nurse to initiate for each family member at all visits. Family members who received the intervention program reported higher satisfaction of needs and lower anxiety levels than those family members who did not receive the program. PMID- 2213093 TI - A comparison of the preoperative concerns of open heart surgery patients and their significant others. AB - This article reports the findings of research about the concerns of open heart surgery (OHS) patients and their significant others (SOs) during the preoperative in-hospital waiting period. Concepts from the Roy Adaptation Model for Nursing framed this study and provided a basis for recognizing the problem, constructing instruments to measure the variable, analyzing and interpreting the data, and drawing implications from the findings. A convenience sample of 21 pairs of OHS and SO subjects reported data while awaiting surgery about demographic characteristics and concerns on self-administered instruments constructed for this research. A multitude of concerns was reported by the subjects, with some similarities and some differences between the OHS patients and their SOs. Implications for practice and theory are drawn, and suggestions for research are made. PMID- 2213094 TI - Nursing interventions for the depressed cardiovascular patient. AB - Patients who have a cardiovascular illness may experience sad feelings that range from normal grief reactions to major depressive episodes. Unresolved depression has been shown to affect long-term recovery and mortality. This article explores the differences in these depressive responses so that nurses will be able to focus their assessments and identify appropriate interventions. PMID- 2213095 TI - Identifying and mobilizing social supports for the cardiac patient's family. AB - This article emphasizes the importance of social supports to the cardiac patient's family as members deal with illness-created stress and needs. The dynamic nature of social support and factors contributing to its complexity are discussed. The article describes approaches to identifying and mobilizing the family's natural social supports. PMID- 2213096 TI - Coping and heart disease. AB - This column reviews three studies on coping that provide nurses with a base for identifying individuals with particular coping needs and styles. The studies focus on Type A behavior and coping. Type A behavior and gender differences, and responses of spouses of patients with a first myocardial infarction. PMID- 2213097 TI - The evaluation process for cardiac transplantation: a case study. AB - The evaluation process for cardiac transplantation can be an anxious and overwhelming period for the patient and family. Time is the unknown variable for the health care team, patient, and family while the cardiac evaluation is being completed. This case study focuses on the evaluation phase of one man being considered for cardiac transplantation in a hospital that had not routinely accommodated such a patient. PMID- 2213098 TI - Intraperitoneal adoptive immunotherapy for peritoneal cancer. PMID- 2213099 TI - Intraperitoneal lymphokine-activated killer-cell and interleukin-2 therapy for malignancies limited to the peritoneal cavity. AB - Autologous lymphokine-activated killer (LAK) cells and recombinant human interleukin-2 (rIL-2) were administered intraperitoneally (IP) to 24 patients with malignancies limited to the peritoneal space. Ten patients had ovarian cancer, 12 had colorectal cancer, and one patient each had endometrial carcinoma and primary small-bowel adenocarcinoma. All ovarian cancer patients, three of twelve colorectal cancer patients, and one patient with endometrial carcinoma had received prior therapy. Patients received IL-2 100,000 U/kg every 8 hours intravenously (IV) for 3 days, and 2 days later underwent daily leukapheresis for 5 days. LAK cells were generated in vitro by incubating the peripheral blood mononuclear cells in IL-2 for 7 days and were then administered IP daily for 5 days through a Tenckhoff catheter (Davol, Inc, Cranston, RI) together with IL-2 25,000 U/kg IP every 8 hours. All but one patient completed at least one cycle of therapy. Toxic side effects included minor to moderate hypotension, fever, chills, rash, nausea, vomiting, abdominal pain and distension, diarrhea, oliguria, fluid retention, thrombocytopenia, and minor elevations of liver function tests; all of these rapidly improved after discontinuation of IL-2. One patient had a grand mal seizure, and one suffered a colonic perforation; these were felt to be treatment-related. IP fibrosis developed in 14 patients and limited repeated cyclic administration of this therapy in five patients. Two of 10 (20%) ovarian cancer patients and five of 12 (42%) colorectal cancer patients had laparoscopy- or laparotomy-documented partial responses. We conclude that LAK cells and rIL-2 can be administered IP to cancer patients, resulting in moderate to severe short-term toxicity and modest therapeutic efficacy. Further investigation of this form of adoptive immunotherapy modified to address the problem of IP fibrosis and with lower IP IL-2 doses is justified by these initial results. PMID- 2213101 TI - Interleukin-2 therapy in patients with metastatic malignant melanoma: a phase II study. AB - Forty-seven patients with metastatic malignant melanoma were treated with two 5 day cycles of 100,000 U/kg recombinant interleukin-2 (IL-2) intravenously (IV) every 4 hours separated by 1 week. This dose and schedule of IL-2 were identical to those used in a previous combined IL-2 and lymphokine-activated killer (LAK) cell phase II clinical trial of the IL-2/LAK Working Group. Patient eligibility criteria, and clinical management guidelines were similar to those used in the previous trial. Forty-six patients were assessable for response. Objective responses were observed in 10 of 46 patients (two complete responses [CRs], eight partial responses [PRs]) or 22% with responses occurring in lung and liver as well as lymph nodes and subcutaneous sites. The median response duration was 8 months. Toxicity was significant; three patients developed myocardial infarction, and one patient died during therapy. Overall the toxicity and response rate for single-agent IL-2 are similar to that observed with IL-2 administered in combination with LAK cells in the previous trial. These results suggest that single-agent therapy with IL-2 when administered in this schedule has significant antimelanoma activity in humans, and that LAK cells generated from peripheral blood add little to the antimelanoma activity of this dose and schedule of IL-2. PMID- 2213100 TI - Therapy of renal cell carcinoma with interleukin-2 and lymphokine-activated killer cells: phase II experience with a hybrid bolus and continuous infusion interleukin-2 regimen. AB - Forty-seven patients with metastatic or unresectable renal cell carcinoma were treated with interleukin-2 (IL-2) and lymphokine-activated killer (LAK)-cell therapy, using a hybrid IL-2 regimen. IL-2 was administered initially by intravenous bolus (10(5) U/kg [Cetus Corp, Emeryville, CA] every 8 hours for 3 days) during the priming phase, and subsequently by continuous infusion (3 x 10(6) U/m2 for 6 days); during this second treatment period, in vitro-generated LAK cells were administered. Despite selection of patients for good performance status (PS) (29, PS 0; 18, PS 1) prior nephrectomy (43 of the 47 patients), and low tumor burden, the response rate was low (two complete [CRs] and two partial responses [PRs], for an overall objective response rate of 9%). Toxicity was comparable to that experienced with the high-dose bolus regimen. These results suggest that the dose and schedule of IL-2 administration may influence the likelihood of response to IL-2 in renal cell carcinoma. PMID- 2213102 TI - Phase I study of interleukin-2 and interferon alfa-2a as outpatient therapy for patients with advanced malignancy. AB - Twenty-six patients were treated in this phase I study with the combination of interleukin-2 (IL2) administered as a continuous infusion and interferon alfa-2a (IFN alpha-2a) administered intramuscularly to patients in an outpatient setting. The maximum-tolerated dose of both agents given as outpatient therapy was 2 x 10(6) U/m2 days 1 to 5 of IL2 and 9 x 10(6) U/m2 days 1, 3, and 5 of IFN alpha-2a for 4 consecutive weeks. A 2- to 4-week rest period was permitted after each 4 weeks of treatment. Fatigue was the treatment-limiting toxicity, and serious clinical or laboratory abnormalities occurred infrequently during this study. Patients with colon cancer metastatic to the liver tolerated treatment worse than patients with other tumors. Twelve of the 15 patients with renal cell cancer were assessable for response determinations. Of these 12 patients, three exhibited complete tumor regression, three have had partial objective regression, and three patients experienced stabilization of rapidly progressive disease. This therapy appears to be well tolerated in an outpatient treatment setting and shows significant activity against advanced renal cell cancer. PMID- 2213103 TI - Multimodal therapy for the management of primary, nonmetastatic Ewing's sarcoma of bone: a long-term follow-up of the First Intergroup study. AB - A total of 342 previously untreated eligible children were entered into the first Intergroup Ewing's Sarcoma Study (IESS) between May 1973 and November 1978. In group I institutions, patients were randomized between treatment 1 (radiotherapy to primary lesion plus cyclophosphamide, vincristine, dactinomycin, and Adriamycin [doxorubicin; Adria Laboratories, Columbus, OH] [VAC plus ADR]) or treatment 2 (same as treatment 1 without ADR), and group II institutions randomized patients between treatment 2 or treatment 3 (same as treatment 2 plus bilateral pulmonary radiotherapy [VAC plus BPR]). The percentages of patients relapse-free and surviving (RFS) at 5 years for treatments 1, 2, and 3 were 60%, 24%, and 44%, respectively. There was strong statistical evidence of a significant advantage in RFS for treatment 1 (VAC plus ADR) versus 2 (VAC alone) (P less than .001) and 3 (P less than .05) and also of treatment 3 versus 2 (P less than .001). Similar significant results were observed with respect to overall survival. Patients with disease at pelvic sites have significantly poorer survival at 5 years than those with disease at nonpelvic sites (34% v 57%; P less than .001). Among pelvic cases, there was no evidence of differing survival by treatment (P = .81), but among nonpelvic cases, there was strong evidence of differing survival by treatment (P less than .001). The overall percentage of patients developing metastatic disease was 44%; the percentages by treatments 1, 2, and 3 were 30%, 72%, and 42%, respectively. The overall incidence of local recurrence was 15%, and there was no evidence that local recurrence rate differed by treatment. Patient characteristics related to prognosis, both with respect to RFS and overall survival experience, were primary site (nonpelvic patients were most favorable) and patient age (younger patients were more favorable). PMID- 2213104 TI - Combined versus sequential chemo-endocrine therapy in advanced prostate cancer: final results of a randomized Southwest Oncology Group study. AB - Cytotoxic chemotherapy has not provided survival benefit in metastatic prostate cancer, although it has been used most frequently in patients with far-advanced, refractory disease. To evaluate the effects of chemotherapy given earlier in the course of the disease, the Southwest Oncology Group (SWOG) performed a randomized trial between September 1982 and October 1986 comparing endocrine therapy (diethylstilbestrol [DES] or orchiectomy) alone followed by cyclophosphamide Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) chemotherapy at progression versus initial combined chemo-endocrine therapy. One hundred forty three patients were registered, and only six were declared ineligible. Patients on the combined chemo-endocrine therapy arm had a slightly higher response rate (63%) compared with endocrine therapy alone (48%). A log-linear model of tumor response and treatment arm adjusted for the stratification factors favored the combination arm (P = .059). Only three of 27 patients on the endocrine therapy alone arm had an objective partial response when crossed over to chemotherapy, while two others had stable disease. Despite the difference in initial response rate, time to treatment failure and survival were identical in the two treatment arms. Seventy-seven percent of patients on the initial endocrine therapy alone arm have died (median survival, 25.6 months) compared with 78% on the chemo endocrine therapy arm (median survival, 22.0 months). No significant effect of treatment on survival was observed even after adjustment for the stratification variables in a Cox regression model. Exploratory survival analyses with patients on both arms combined did show a marginally significant time to treatment failure and survival advantage for patients treated with DES rather than orchiectomy as initial endocrine therapy. Eighty-six percent of patients treated by orchiectomy have died compared with only 65% of those treated with DES. These data do not support the addition of cytotoxic chemotherapy to initial endocrine therapy in patients with metastatic prostate cancer. PMID- 2213105 TI - Hepatic venoocclusive disease in autologous bone marrow transplantation of solid tumors and lymphomas. AB - Retrospective review of 291 solid tumor and lymphoma patients undergoing autologous bone marrow transplantation (BMT) was performed to determine the influence of pretransplant characteristics and preparative regimen to the development of hepatic venoocclusive disease (VOD). Twelve patients (4.1%) developed a clinical syndrome of right upper quadrant (RUQ) tenderness or hepatomegaly, jaundice, and ascites, with or without encephalopathy, within 40 days of marrow reinfusion. Evidence of metastatic liver disease was the only pretransplant characteristic predictive for VOD (P = .0002). Sex, age, histology, hepatitis B serology, and elevated liver function tests were not predictive. No individual preparative agent had a significant effect on the development of VOD. However, a single 2-hour infusion of carmustine (BCNU) (greater than or equal to 450 mg/m2) led to an increased incidence of VOD when compared with the same dose administered in a fractionated schedule (P = .0258) when given with two other chemotherapeutic agents. Seven of eight autopsy specimens confirmed the clinical diagnosis of VOD. The four patients in whom clinical VOD resolved had lower median peak bilirubins (7.3 v 15.9 mg/dL), lower median peak creatinines (2.1 v 4.1 mg/dL), and relatively quick engraftment of neutrophils (mean, 18.7 days). One of the four patients in whom VOD resolved had other grade 4 (life threatening) toxicities in contrast to eight of eight who succumbed. In summary, VOD is an uncommon complication in autotransplantation of solid tumors and lymphomas. Our data suggest caution in selecting patients with known metastatic liver disease and consideration of a fractionated BCNU schedule especially in combination with other alkylating agents. PMID- 2213106 TI - Bone marrow transplantation for myelodysplasia and secondary acute nonlymphoblastic leukemia. AB - Twenty-three patients with primary myelodysplasia (MDS) or secondary myelodysplasia/acute nonlymphocytic leukemia (MDS/ANLL) were treated with allogeneic or syngeneic bone marrow transplantation (BMT). Only one patient was in a chemotherapy-induced hematologic remission. Graft-versus-host disease prophylaxis included methotrexate, methotrexate plus cyclosporine, cyclosporine, or T-cell depletion using one of two anti-CD5 monoclonal antibodies. For patients with primary MDS, the median age was 19 years (range, 11 to 41 years) and the actuarial disease-free survival was 56% +/- 21% (median follow-up, 2 years; range, 0.8 to 5 years). There were three graft failures (two with autologous recovery) and two early deaths. Outcome appeared to be related to French-American British (FAB) classification. For patients with secondary MDS/ANLL, the median age was 28 years (range, 3 to 16 years) and the actuarial disease-free survival was 27% +/- 13% (median follow-up, 5 years; range, 2.5 to 8.5 years). There were no graft failures, two relapses, and four early deaths. The presence of marrow fibrosis per se did not predict for graft failure (P = .21); however, the use of T-cell depleted marrow in patients with marrow fibrosis resulted in graft failure in three of five individuals. Our results suggest that in patients with primary MDS or secondary MDS/ANLL, BMT should be considered early in the course of the disease, and that attempts at inducing a remission prior to BMT appeared to be unnecessary. In MDS patients with marrow fibrosis, T-cell depletion should be avoided. PMID- 2213107 TI - Response of oral leukoplakia to beta-carotene. AB - Leukoplakia is associated with increased risk of oral cancer and is considered a premalignant lesion. Retinoids, particularly 13-cis retinoic acid, can frequently reverse leukoplakia. However, these drugs have considerable toxicity and are not suitable for large-scale use in the prevention of oral cancer. Beta-carotene is a naturally occurring, nontoxic carotenoid with biologic properties that suggest that it might be efficacious against oral leukoplakia. In 1986, we began a randomized study of 13-cis retinoic acid (1 mg/kg/d) versus beta-carotene (30 mg/d) in leukoplakia. However, owing to the marked differences in toxicity between the two compounds outlined in the consent form, 11 of the initial 16 eligible patients refused to participate unless they were "guaranteed" beta carotene. Therefore, the study design was changed to a phase II trial of beta carotene in which the compound was given daily for 3 months. Responding patients were continued for another 3 months of treatment. All lesions were examined histologically at entry. Responses were monitored by bidimensional measurements and photography done at entry, then monthly while on treatment and at study completion. Twenty-four evaluable patients were treated, and 17 had major responses (two complete, 15 partial), a response rate of 71% (95% confidence limits, 53% to 89%). There was no significant toxicity requiring drug discontinuation or dose reduction. These results indicate that beta-carotene has substantial activity in oral premalignancy. Because of its lack of toxicity, it is an excellent candidate for a preventive agent for oral cancer. PMID- 2213108 TI - Phase I study of repeated cycles of high-dose cyclophosphamide, etoposide, and cisplatin administered without bone marrow transplantation. AB - Forty-two patients with advanced malignancy judged unlikely to respond to standard treatment received high-dose combination chemotherapy with cyclophosphamide, etoposide, and cisplatin in a phase I trial. Twenty-two of these patients who had at least a partial response (PR) to the first cycle of therapy received a second cycle, and eight patients received three or more cycles of therapy. Bone marrow replacement was not used. The maximum-tolerated doses (MTDs) were cyclophosphamide 2.5 g/m2 on days 1 and 2; etoposide 500 mg/m2 on days 1, 2, and 3; and cisplatin 50 mg/m2 on days 1, 2, and 3. Hematologic toxicity was not dose-limiting by study design. Recovery to an absolute granulocyte count above 100/microL occurred at a median of 9 days from onset (range, 3 to 23 days) at the MTD. Recovery was delayed after the third cycle. Only one patient on his third cycle failed to recover peripheral blood counts and died of sepsis an day 43. Hematologic toxicity was not dose-dependent. Nonhematologic toxicities included emesis, fatigue, alopecia, diarrhea, and anorexia and were generally well tolerated. The dose-limiting toxicities were fatal pulmonary or cardiac toxicities in five of nine patients treated at the highest dose level. Patients likely to do well can be selected by tumor type, response to prior therapy, and performance status. Nine of 36 assessable patients had a complete response (CR) and 13 a PR for a response rate of 61%. Five patients (12%) remain alive and free of disease at 15 to 32 months. Repeated cycles of dose-intensive combination therapy can produce long-term disease-free remissions in patients with refractory tumor types. The toxicity of the regimen is acceptable if patients are carefully selected. PMID- 2213109 TI - Pharmacodynamics in cancer therapy. AB - Our understanding of anticancer pharmacodynamics, and the relationships between pharmacologic measurements and clinical effects, has grown markedly in recent years due to advances in analytical and computational technology. Although methotrexate plasma levels have been empirically used to guide leucovorin dosing during high-dose methotrexate therapy, there has been no other standard use of therapeutic drug monitoring in oncology. More recently, investigators have attempted to titrate precisely the dose of antineoplastic agents based on previously derived models and real-time analysis of plasma drug or tissue concentrations. Studies have been completed or are in progress using hexamethylene bisacetamide, etoposide, teniposide, fluorouracil (FUra), and cytarabine (ara-C). Future studies will focus on optimal sampling strategies, analysis of intermediate biochemical end points, combination chemotherapy, modulation by colony-stimulating factors, and more sophisticated pharmacodynamic models. PMID- 2213110 TI - Antibiotic prophylaxis to prevent catheter-related infections in recombinant interleukin-2-treated patients. PMID- 2213111 TI - Evidence of "stage shift" in IRS studies? PMID- 2213112 TI - Sensitization of C6 glioma to carboplatin cytotoxicity by hyperthermia and thymidine. AB - Thymidine (a nucleoside metabolite) and 41.8 degrees C hyperthermia were used to sensitize C6 glioma cells to carboplatin cytotoxicity in vitro. Clinically achievable thymidine concentrations (0, 200, 400, or 1000 micrograms/ml X 24 hours) significantly enhanced carboplatin killing. Clinically achievable hyperthermia exposures (40.5 or 41.8 degrees C X 1 hour) also enhanced carboplatin killing; 41.8 degrees C was more effective than was 40.5 degrees C. Thymidine and 41.8 degrees C hyperthermia together enhanced carboplatin killing significantly more than did the thymidine-carboplatin or hyperthermia-carboplatin combinations. These results illustrate the concept of 'combination chemosensitization' for simultaneously addressing the divergent drug resistance mechanisms of malignant gliomas. PMID- 2213113 TI - Relationship between of blood flow, glucose metabolism, protein synthesis, glucose and ATP content in experimentally-induced glioma (RG1 2.2) of rat brain. AB - In experimental RG1 2.2 glioma of rat brain, local blood flow, glucose utilization, protein synthesis, glucose and ATP content were measured by means of triple tracer autoradiography and bioluminescence technique, respectively, to determine hemodynamic and metabolic thresholds for local tumor energy failure. Perfusion thresholds were estimated at tumor blood flow values of 69.0 +/- 0.1 ml/100 g/min (estimate +/- standard error) and of 69 +/- 7.1 ml/100 g/min for the beginning of the decline in regional ATP and glucose content, respectively. Metabolic thresholds were derived at tumor glucose utilization values of 70.6 +/- 8.3 mumol/100 g/min for reduced protein synthesis, of 55.0 +/- 0.2 mumol/100 g/min for the decrease in glucose content, and 34.7 +/- 4.7 mumol/100 g/min for decline in ATP content. Our results suggest that blood flow limits glucose supply to tumor tissue at much higher flow rates than in normal brain which, in turn, is associated with a decrease in tumor glucose utilization. A reduction and not an increase in tumor glucose availability could be a more appropriate strategy for the induction of energy failure in tumors. PMID- 2213114 TI - Alkaline phosphatase level in CSF in various brain tumors and pulmonary carcinomatous meningitis. AB - Twenty-six patients with various brain tumors or carcinomatous meningitis were examined for alkaline phosphatase (ALP) in the cerebrospinal fluid. ALP enzyme levels were compared with the respective levels in control groups of 75 patients with epilepsy, stroke, bacterial and viral meningitis and intervertebral disc prolapse. Extremely high ALP levels in CSF (9516 mu/l, 1425 mu/l, and 871 mu/l) were found in patients with pulmonary carcinomatous meningitis. Among all other patients with brain tumors, ALP levels in CSF were in the normal range. Examination of ALP in serum yielded normal results in all patients. In patients with pulmonary carcinomatous meningitis, the enzyme level in CSF was examined during various stages of radiotherapy and chemotherapy. Decreased ALP enzyme level was found during treatment followed by recurring rising levels a month after the treatment coinciding with clinical relapse. No correlation was found between the level of ALP enzyme and the biochemical and cellular content of the CSF during the various stages of treatment. PMID- 2213115 TI - Prognostic factors for high-grade malignant glioma: development of a prognostic index. A Report of the Medical Research Council Brain Tumour Working Party. AB - Although the prognosis of high grade malignant glioma patients is generally poor, it is possible to identify groups of patients with varying prognoses. Basing our results on the first MRC glioma study, multivariate methods were used to identify prognostic factors independently associated with the length of survival. Young age, the presence of fits, especially of long duration, extensive surgical removal of tumour and good clinical performance status were found to be the most important predictors of longer survival. The effect of tumour grade (3 or 4) was not significant, being considerably diluted by an association with extent of neurosurgery. A prognostic index was derived which split the patients into 6 groups of varying prognoses, with 2-year survival rates of between 1 and 32%. The results were verified in patients entered into a subsequent MRC trial. The successful identification of different prognostic groups suggests the use of this index as an aid in making treatment decisions for individual patients, and in interpreting the results of uncontrolled phase II studies. PMID- 2213116 TI - Paraneoplastic cerebellar degeneration associated with multiple myeloma--3.4 years follow up. AB - A 57 year old female patient demonstrated subacute generalized cerebellar symptoms and the investigations which were done exhibited that the clinical picture was due to the remote effect of multiple myeloma. In this case of paraneoplastic cerebellar degeneration, MRI showed cerebellar vermian atrophy when the brain CT scan was negative. Diagnosis of multiple myeloma was possible only on about the 17th month of the illness when monoclonal gammapathy-IgG in serum of the patient and abnormal plasma cells of 13% in her bone marrow biopsy were exhibited. Bence-Jones proteinuria with kappa light chain was found in the 3.4th year of the illness. Paraneoplastic cerebellar degeneration disabled the patient in 3-4 months and remained as an irreversible process during the 3.4 years in which she was followed until her death. Chemotherapy for multiple myeloma did not affect the cerebellar syndrome. PMID- 2213117 TI - A phase II study of diaziquone in children with recurrent or progressive primary brain tumors: a report from the Childrens Cancer Study Group. AB - Seventy-five children with recurrent, progressive or metastatic primary brain tumors were treated with aziridinylbenzoquinone (AZQ; Diaziquone) at 9 mg/m2/day by 30-minute intravenous infusion for five days every three weeks. Sixty-six patients were evaluable for response by imaging studies. There were five partial responses and one complete response for a combined response rate of 9%. A complete response lasting for 35+ months occurred in one of twelve patients with metastatic or locally recurrent ependymoma. Objective responses were also seen in patients with primitive neuroectodermal tumors (PNET) (1/8), low-grade glioma (1/6), and primary central nervous system lymphoma (1/1). Stable disease of greater than six months duration was seen in patients with ependymoma, PNET and medulloblastoma. Profound and prolonged myelo-suppression was the significant toxicity observed. As administered in this study, AZQ has marginal activity and severe toxicity. PMID- 2213118 TI - Temporal lobe ganglioglioma in refractory epilepsy: CT and MR in three cases. AB - Three patients (ages 5, 16 and 21 years) with chronic, refractory, partial epilepsy and temporal lobe ganglioglioma were evaluated for surgical treatment. Noncontrast CT revealed a low attenuation, cystic temporal lesion in 2 patients. One neoplasm demonstrated focal calcification and temporal altrophy, while the other had mass effect and surrounding edema. Contrast enhancement of the mass was seen in one instance. Non-contrast and post-contrast CT were completely normal in the remaining patient. MR was abnormal in both patients in which it was performed (including the patient with a normal CT examination). Lesions were hyperintense on T2W inmages and iso-to-hypointense on T1W images when compared to normal parenchyma. Regions of calcification were missed on standard spin-echo sequences. Continuous video EEG monitoring captured habitual partial seizures in all patients; focal onset correlated with tumor location in each instance. Intraoperative electrocorticography corroborated the EEG results. Two of three patients underwent gross total resection. Pathologic features were characteristic of ganglioglioma in all instances. All patients have been seizure-free postoperatively [mean follow-up: 16 months (range 13-18 months)] and without evidence of tumor recurrence. Although ganglioglioma is an unusual cause of refractory temporal lobe epilepsy, our short term follow-up suggests excellent outcome with both partial and gross total resection. PMID- 2213119 TI - Low dose rate radiotherapy for transplantable gliosarcoma in the rat brain. AB - Interstitial brachytherapy with low energy radionuclides is becoming widely used in conjunction with external beam radiotherapy in the treatment of primary malignant gliomas of the brain. Few radiobiological studies have been carried out with low dose rate brachytherapy for brain tumors. Since we have recently developed a non-invasive low dose rate radiotherapy model for the treatment of transplantable 9L gliosarcoma growing in the rat brain, we carried out a series of radiobiological studies to determine the dose rate effect on the tumor and normal brain tissue. Using TCD50 (the radiation dose to control 50% tumor control) as the endpoints, we obtained the results indicating that the tumor control rate was highly dependent on the dose rate and the total dose delivered to the tumor. The TCD50 of dose rates ranging from 100 cGy/min, 120 cGy/hr, and 40 cGy/hr were 25 Gy, 80 Gy, and 100 Gy, respectively. The normal tissue effects were most pronounced with high dose rate irradiation (100 cGy/min). The LD50 for high dose rate irradiation to the whole brain was 29 Gy. In contrast, the majority of animals treated with low dose rate radio-therapy behaved quite normal up to a year follow-up. The late histopathological changes of the irradiated brain usually consisted of vascular and white matter necrosis, although the extent of such changes showed a considerable individual variation within the long term survivors. PMID- 2213120 TI - Background-induced flicker enhancement in cat retinal horizontal cells. I. Temporal and spectral properties. AB - 1. Dim backgrounds can enhance small-spot flicker responses of cat retinal horizontal cells by a factor of 2 or more. 2. Intracellular marking with horseradish peroxidase (HRP) reveals that this enhancement effect occurs in--but is not necessarily limited to--the cone-connected, A-type horizontal cell. 3. Flicker amplitudes decrease over a frequency range from 3 to 36 Hz of square-wave photic stimulation. There is little evidence of flicker-response enhancement at 3 Hz. Flicker-response enhancement is typically 2-6 times larger at 35 than at 6 Hz. 4. Inspection of flicker waveforms indicates both a scaling-up of response signals with backgrounds and a distortion composed of 2- to 5-ms-latency decrease, expressed primarily within a quick component of OFF-repolarization. 5. Flicker enhancement first increases as a function of background irradiance and then decreases. The increasing limb has the dynamic range and spectral sensitivity of cat rods (507-nm peak). Enhancement is maintained during rod after effects. The decreasing limb of the background-versus-intensity function results from light adaptation of cat, long-wavelength (red) cones. 6. The flicker responses themselves peak spectrally at approximately 555 nm and reflect only the activity of cat long-wavelength (red) cones, without evidence of intermixing of other photoreceptor mechanisms. 7. Thus within the first synaptic layer of the cat visual system, rod signals interact with the flicker responses of red cones, both increasing cone-signal amplitudes and modifying cone-signal waveforms. 8. The results are closely analogous to "suppressive rod-cone interaction" (SRCI) as described in human psychophysics. 9. An outer-plexiform-layer circuit involving rods, horizontal cells and cones may mediate rod-induced enhancement of cone flicker. This being the case, notions of horizontal-cell feedback interactions with cones may have to be modified and extended. A specific feedback model is elaborated in the companion paper. PMID- 2213121 TI - Background-induced flicker enhancement in cat retinal horizontal cells. II. Spatial properties. AB - 1. Intracellular recordings have been made from cat retinal horizontal cells stimulated with flickering test spots. Dim backgrounds increase flicker amplitudes in response to small but not large test stimuli. 2. This background induced flicker enhancement has been measured for different slit- and square-test stimulus widths and the results compared with two spatial models for the enhancement effect. 3. In the "dark test-region" model it is argued that rods within the test region are unresponsive to background stimuli because of prior saturation by the test stimulus. Background-evoked rod signals decay passively from regions outside the test stimulus through a syncytial network into the recording site, where they act on the cone-to-horizontal-cell synapse, increasing its gain. 4. In the "changing length-constant" model rod signals reduce the length constant of a syncytial network by uncoupling the cells within it. This causes an increased response to small but not large test stimuli. 5. Both models are analytically evaluated with the use of a conductive-sheet approximation to the syncytial network. Expressions are derived for network polarization [(V(0, 0)] as a function of stimulus size. The specific stimulus shapes considered are disks, rectangles, slits, and squares in both bright and dark varieties. From these expressions predictions of response enhancement as a function of stimulus size are made for both models. 6. The dark test-region model provides for an exponential decay of flicker enhancement as a function of slit width but a steeper-than-exponential decay with the width of squares, in close agreement with experimental data. 7. The changing length-constant model makes qualitatively similar predictions. Flicker enhancement declines nearly exponentially with slit width. For square-shaped test stimuli the predicted decline of flicker enhancement with size is somewhat shallower than either the dark test-region model curve or the experimentally determined curve. 8. As recorded in the same set of cells and under the same set of stimulus conditions (with the use of both slit- and square-test stimuli), the mean length constant of the peak-to-peak flicker component in the horizontal-cell response is 168 +/- 18 (SE) microns with the background and 232 +/- 45 microns in the dark. The mean length constant for the background-induced flicker enhancement, as fit by dark test-region-model curves, is 186 +/- 22 microns (n = 9).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213122 TI - Temporal encoding of two-dimensional patterns by single units in primate primary visual cortex. I. Stimulus-response relations. AB - 1. Previously we developed a new approach for investigating visual system neuronal activity in which single neurons are considered to be communication channels transmitting stimulus-dependent codes in their responses. Application of this approach to the stimulus-response relations of inferior temporal (IT) neurons showed that these carry stimulus-dependent information in the temporal modulation as well as in the strength of their responses. IT cortex is a late station in the visual processing stream. Presumably the neuronal properties arise from the properties of the inputs. However, the discovery that IT neuronal spike trains transmit information in stimulus-dependent temporally modulated codes could not be assumed to be true for those earlier stations, so the techniques used in the earlier study were applied to single-striate cortical neurons in the studies reported here. 2. Single-striate cortical neurons were recorded from three awake, fixating rhesus monkeys. The neurons were stimulated by two sets of patterns. The first set was made up of 128 black-and-white patterns based on a complete, orthogonal set of two-dimensional Walsh-Hadamard functions. These stimuli appear as combinations of black-and-white rectangles and squares, and they fully span the range of all possible black-and-white pictures that can be constructed in an 8 x 8 grid. Except for the stimulus that appeared as an all white or all-black square, each stimulus had equal areas of white and black. The second stimulus set was made up of single bars constructed in the same 8 x 8 grid as the Walsh stimuli. These were presented both as black against a gray background and white against a gray background. The stimuli were centered on the receptive field, and each member of the stimulus set was presented once before any stimulus appeared again. 3. The responses of 21 striate cortical neurons were recorded and analyzed. Two were identified as simple cells and the other 19 as complex cells according to the criteria originally used by Hubel and Wiesel. The stimulus set elicited a wide variety of response strengths and patterns from each neuron. The responses from both the bars and the Walsh set could be used to differentiate and classify simple and complex cells. 4. The responses of both simple and complex cells showed striking stimulus-related strength and temporal modulation. For all of the complex cells there were instances where the responses to a stimulus and its contrast-reversed mate were substantially different in response strength or pattern, or both.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213123 TI - Temporal encoding of two-dimensional patterns by single units in primate primary visual cortex. II. Information transmission. AB - 1. Previously, we studied how picture information was processed by neurons in inferior temporal cortex. We found that responses varying in both response strength and temporal waveform carried information about briefly flashed stationary black-and-white patterns. Now, we have applied that same paradigm to the study of striate cortical neurons. 2. In this approach the responses to a set of basic black and white pictures were quantified through use of a set of basic waveforms, the principal components (extracted from all the responses of each neuron). We found that the first principal component, which corresponds to the response strength, and others, which correspond to different basic temporal activity patterns, were significantly related to the stimuli, i.e., the stimulus drove both the response strength and its temporal pattern. 3. Our previous study had shown that, when information theory was used to quantify the stimulus response relation, inferior temporal neurons convey over twice as much information in a response code that includes temporal modulation as in a response code that includes only the response strength. This study shows that striate cortical neurons also carry twice as much information in a temporal code as in a response strength code. Thus single visual neurons at both ends of a cortical processing chain for visual pattern use a multidimensional temporal code to carry stimulus-related information. 4. These results support our multiplex-filter hypothesis, which states that single visual system neurons can be regarded as several simultaneously active parallel channels, each of which conveys independent information about the stimulus. PMID- 2213124 TI - Evidence for restricted central convergence of cutaneous afferents on an excitatory reflex pathway to medial gastrocnemius motoneurons. AB - 1. We previously reported that excitatory postsynaptic potentials (EPSPs) produced by low-threshold electrical stimulation of the caudal cutaneous sural nerve (CCS) occur preferentially and with the shortest central latencies in the medial gastrocnemius (MG) portion of the triceps surae motor nuclei. The present study employs the spatial facilitation technique to assess interneuronal convergence on the short-latency excitatory pathway from CCS to MG by several other ipsilateral hindlimb afferents [the lateral cutaneous sural (LCS), caudal cutaneous femoral (CCF), saphenous (SAPH), superficial peroneal (SP), posterior tibial (TIB), and posterior articular (Joint) nerves]. 2. Spatial facilitation of CCF EPSPs in MG motoneurons was demonstrated with conditioning stimulation of the LCS, CCF, SAPH, SP, and TIB nerves, but was most readily and consistently observed with CCF conditioning. Facilitation of CCS and CCF EPSPs was obtained in individual MG motoneurons with a wide range of condition-test intervals. 3. CCF EPSPs in MG motoneurons produced by twice threshold (2T) afferent stimulation had a mean latency of 4.8 ms and often appeared as slowly rising, asynchronous potentials. On the other hand, 2T CCS EPSPs had a mean latency of 2.8 ms and appeared as sharper rising, less variable depolarizations. The optimum condition test interval for facilitation of CCS and CCF EPSPs was found to be 5.2 ms on average, with CCS stimulation delayed from that of CCF. The longer latency of CCF EPSPs and the finding that the minimum condition-test interval was on the order of 3.9 ms suggests that convergence occurs late in the excitatory CCF pathway to MG motoneurons. 4. Convergence between excitatory pathways to MG from CCF and CCS afferents is discussed with regard to the original observations of Hagbarth on the location of cutaneous receptive fields and excitation of ankle extensors. In addition, evidence for the segregation of these specialized reflex pathways from those involved in general flexion reflexes is discussed. PMID- 2213125 TI - Behavior of accessory abducens and abducens motoneurons during eye retraction and rotation in the alert cat. AB - 1. The activity of both accessory abducens (Acc Abd) and abducens (Abd) motoneurons (Mns) was recorded in the alert cat during eye retraction and rotational eye movements. Cats were fitted with two scleral coils, one measured rotational eye movements directly and the other retraction by distinguishing the translational component. 2. Acc Abd and Abd Mns were identified following antidromic activation from electrical stimulation of the ipsilateral VIth nerve. 3. In response to corneal air puffs, bursts of spikes were produced in all (n = 30) Acc Abd Mns. The burst began 7.2 +/- 1.2 (SD) ms after onset of the air puff and 8.9 +/- 1.9 ms before eye retraction. 4. Acc Abd Mns were silent throughout all types of rotational eye movements, and tonic activity was not observed during intervals without air-puff stimulation. 5. In contrast, all (n = 50) identified Abd Mns exhibited a burst and/or pause in activity preceding and during horizontal saccades as well as a tonic activity proportional to eye position. 6. Only 10% of Abd Mns fired a weak burst of spikes in response to air-puff stimulation. 7. We conclude that Acc Abd Mns are exclusively involved in eye retraction in the cat and that only a few Abd Mns have an eye-retraction signal added to their eye position and velocity signals. Thus any rotational eye movement response described in retractor bulbi muscle must result from innervation by Mns located in the Abd and/or the oculomotor nuclei. 8. The organization of the prenuclear circuitry and species variation are discussed in view of the nictiating membrane extension response measured in associative learning. PMID- 2213126 TI - Sensitivities of cells in anteroventral cochlear nucleus of cat to spatiotemporal discharge patterns across primary afferents. AB - 1. This study tested the hypothesis that a cell in the anteroventral cochlear nucleus (AVCN) that receives convergent input from auditory nerve (AN) fibers can be sensitive to the temporal pattern of discharges on the set of AN fibers providing its input. 2. The temporal discharge pattern across the population of low-frequency AN fibers was manipulated by varying the phase spectra of complex stimuli that had fixed, flat magnitude spectra. By introducing a phase shift with variable slope at a particular frequency, the relative times of discharge of phase-locked neurons with different characteristic frequencies (CFs) could be varied. In this manner the overall spatiotemporal discharge pattern across the array of AN fibers was systematically manipulated. 3. Some low-frequency cells in the AVCN were sensitive to changes in the slope of the phase transition of the complex stimulus. The cells that were sensitive came from several different cell types in the AVCN. Their responses were consistent with the hypothesis that these cells were sensitive to the temporal relationships between discharges on their primary inputs and that they received inputs with different CFs, because the phase shifts introduced relative time differences between different frequencies. 4. Other cells were not sensitive to the degree of phase shift of the stimulus. This insensitivity implied either that these cells received inputs of the same, or nearly the same, CF, or that they were not sensitive to the time differences introduced by these changes in the phase spectra, or both. 5. The cells that were sensitive to the manipulations of the phase spectrum were located in the posterior region of anterior AVCN and in the posterior region of AVCN and thus were presumably either globular bushy, small spherical bushy, or stellate cells. No sensitive cells were located in the most anterior region of the AVCN, where large spherical bushy cells are located. 6. Temporal discharge patterns across the AN population in response to complex stimuli change as a function of level. Accordingly, the sensitivity of neurons to changes in the phase transitions of the complex stimuli used in this study was often affected by the level of the stimulus. 7. The sensitivity to changes in the phase spectrum was a frequency specific effect. That is, a cell was most sensitive to changes made in phase that were centered near its CF and less sensitive to changes in phase that were introduced at frequencies below or above CF.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213128 TI - Primate frontal eye fields. III. Maintenance of a spatially accurate saccade signal. AB - 1. We studied the activity of single neurons in the monkey frontal eye fields during oculomotor tasks designed to assess the activity of these neurons when there was a dissonance between the spatial location of a target and its position on the retina. 2. Neurons with presaccadic activity were first studied to determine their receptive or movement fields and to classify them as visual, visuomovement, or movement cells with the use of the criteria described previously (Bruce and Goldberg 1985). The neurons were then studied by the use of double-step tasks that dissociated the retinal coordinates of visual targets from the dimensions of saccadic eye movements necessary to acquire those targets. These tasks required that the monkeys make two successive saccades to follow two sequentially flashed targets. Because the second target disappeared before the first saccade occurred, the dimensions of the second saccade could not be based solely on the retinal coordinates of the target but also depended on the dimensions of the first saccade. We used two versions of the double-step task. In one version neither target appeared in the cell's receptive or movement field, but the second eye movement was the optimum amplitude and direction for the cell (right-EM/wrong-RF task). In the other the second stimulus appeared in the cell's receptive field, but neither eye movement was appropriate for the cell (wrong EM/right-RF task). 3. Most frontal-eye-field cells discharged in the right EM/wrong-RF version of the double-step task. Their discharge began after the first saccade and continued until the second saccade was made. They usually discharged even on occasional trials in which the monkey failed to make the second saccade. They discharged much less, or not at all, in the wrong-EM/right RF version of the double-step paradigm. Thus most presaccadic cells in the frontal eye fields were tuned to the dimensions of saccadic eye movements rather than to the coordinates of retinal stimulation. 4. Eleven movement cells (including 1 which also had independent postsaccadic activity for saccades opposite its presaccadic movement field) were studied, and all had significant activity in the right-EM/wrong-RF task. 5. Almost all (28/32) visuomovement cells, including 12 with independent postsaccadic activity, discharged in the right-EM/wrong-RF task. None of the four that failed had independent postsaccadic activity. 6. The majority (26/40) of visual cells were responsive in the right EM/wrong-RF task.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213127 TI - Interaural time sensitivity in medial superior olive of cat. AB - 1. We studied the sensitivity of cells in the medial superior olive (MSO) of the anesthetized cat to variations in interaural phase differences (IPDs) of low frequency tones and in interaural time differences (ITDs) of tones and broad-band noise signals. Our sample consisted of 39 cells histologically localized to the MSO. 2. All but one of the cells had characteristic frequencies less than 3 kHz, and 79% were sensitive to ITDs and IPDs. More than one-half (56%) of the cells responded to monaural stimulation of either ear, and both the binaural and monaural responses were highly phase locked. All of the cells that were sensitive to IPDs and monaurally driven by either ear responded in accord with that predicted by the coincidence model of Jeffress, as judged by comparisons of the phases at which the monaural and binaural responses occurred. The optimal IPDs were tightly clustered between 0.0 and 0.2 cycles. Most cells exhibited facilitation of the response at favorable ITDs and inhibition at unfavorable ITDs compared with the monaural responses. 3. Cells in the MSO exhibited characteristic delay, as judged by a linear relationship between the mean interaural phase and stimulating frequency. Characteristic phases were clustered near 0 indicating the most cells responded maximally when the two input tones were in phase. With the use of the binaural beat stimulus we found no differential selectivity for either the direction or speed of interaural phase changes. 4. The cells were also sensitive to ITDs of broad-band noise signals. The ITD curve in response to broad-band noise was similar to that predicted by the composite curve, which was calculated by linearly summating the tonal responses over the frequencies in the response area of the cell. Most (93%) of the peaks of the composite curves were between 0 and +400 microseconds, corresponding to locations in the contralateral sound field. Moreover, computer cross correlations of the monaural spike trains were similar to the ITD curve generated binaurally for both correlated and uncorrelated noise signals to the two ears. Thus our data suggest that the cells in the MSO behave much like cross correlators. 5. By combining data from different animals and lcoating each cell on a standard MSO, we found evidence for a spatial map of ITDs across the anterior-posterior (A-P) axis of the MSO.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213129 TI - Gaze control in the cat: studies and modeling of the coupling between orienting eye and head movements in different behavioral tasks. AB - 1. Orienting movements, consisting of coordinated eye and head displacements, direct the visual axis to the source of a sensory stimulus. A recent hypothesis suggests that the CNS may control gaze position (gaze = eye-relative-to-space = eye-relative-to-head + head-relative-to-space) by the use of a feedback circuit wherein an internally derived representation of gaze motor error drives both eye and head premotor circuits. In this paper we examine the effect of behavioral task on the individual and summed trajectories of horizontal eye- and head orienting movements to gain more insight into how the eyes and head are coupled and controlled in different behavioral situations. 2. Cats whose heads were either restrained (head-fixed) or unrestrained (head-free) were trained to make orienting movements of any desired amplitude in a simple cat-and-mouse game we call the barrier paradigm. A rectangular opaque barrier was placed in front of the hungry animal who either oriented to a food target that was visible to one side of the barrier or oriented to a location on an edge of the barrier where it predicted the target would reappear from behind the barrier. 3. The dynamics (e.g., maximum velocity) and duration of eye- and head-orienting movements were affected by the task. Saccadic eye movements (head-fixed) elicited by the visible target attained greater velocity and had shorter durations than comparable amplitude saccades directed toward the predicted target. A similar observation has been made in human and monkey. In addition, when the head was unrestrained both the eye and head movements (and therefore gaze movements) were faster and shorter in the visible- compared with the predicted-target conditions. Nevertheless, the relative contributions of the eye and head to the overall gaze displacement remained task independent: i.e., the distance traveled by the eye and head movements was determined by the size of the gaze shift only. This relationship was maintained because the velocities of the eye and head movements covaried in the different behavioral situations. Gaze-velocity profiles also had characteristic shapes that were dependent on task. In the predicted-target condition these profiles tended to have flattened peaks, whereas when the target was visible the peaks were sharper. 4. Presentation of a visual cue (e.g., reappearance of food target) immediately before (less than 50 ms) the onset of a gaze shift to a predicted target triggered a midflight increase in first the eye- and, after approximately 20 ms, the head-movement velocity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213131 TI - Mechanisms of depolarizing inhibition at the crayfish giant motor synapse. II. Quantitative reconstruction. AB - 1. The relative strengths of four mechanisms of depolarizing synaptic inhibition described in the previous paper were evaluated with an electrical model of the giant motor synapse (GMS) and postsynaptic region of the motor giant motoneuron (MoG). 2. The model consists of one compartment that represents the presynaptic region of the medial giant (MG) interneuron and three compartments that represent the postsynaptic region and proximal axon of the MoG. The presynaptic MG compartment is linked to a postsynaptic MoG compartment by a rectifying conductance that represents the GMS. Each compartment consists of parallel paths to ground for active and/or passive membrane currents. 3. Parameter values of the model were set so the MG compartment would replicate an MG impulse and the MoG compartments would replicate the current-clamp, voltage-clamp, and synaptic responses of a single MoG neuron described in the previous paper. The Hodgkin Huxley equations described voltage-sensitive sodium and potassium currents. 4. Comparison of the MoG compartment currents that mediate an inhibited excitatory postsynaptic potential (EPSP) [triggered during a depolarizing inhibitory postsynaptic potential (d-IPSP)] with those of an uninhibited EPSP indicate that all four mechanisms have significant inhibitory effects. Reverse bias of the GMS by the d-IPSP reduced the GMS current by 65 nA (12%). The remaining inward current was further reduced by a 243-nA outward current through the inhibitory postsynaptic conductance. The d-IPSP inactivated sodium conductance so the inward sodium current evoked by the EPSP was reduced by 319 nA (-68%). The d-IPSP reduced the latency for potassium activation by the EPSP so that the outward potassium current coincided with the inward sodium current and reduced the net inward current by 100 nA. Together, these mechanisms reduced the EPSP amplitude by 69%. 5. The resting potential of MoG is normally 15 mV more positive than MG rest potential, but in some preparations this difference may be as much as 25 mV or as little as 0 mV. Corresponding differences in the rest potentials of the MoG and MG models have little effect on the amplitude of the model MoG EPSP because changes in the inward synaptic and sodium currents are balanced by corresponding changes in the outward potassium current. PMID- 2213130 TI - Mechanisms of depolarizing inhibition at the crayfish giant motor synapse. I. Electrophysiology. AB - 1. Mechanisms of depolarizing synaptic inhibition were investigated at the crayfish giant motor synapse with the use of two-electrode current- and voltage clamp techniques. Depolarizing inhibitory postsynaptic potentials (d-IPSPs) of between 5 and 15 mV in amplitude are produced there in the motor giant motoneuron (MoG) by motor giant inhibitor (MoGI) interneurons. 2. Three mechanisms of inhibition are activated by the d-IPSP: inactivation of a voltage-sensitive inward current (probably sodium), activation of the delayed rectifier, and reverse bias of the electrically rectifying giant motor synapse (GMS). These mechanisms supplement the inhibition produced by a gamma-aminobutyric acid (GABA) mediated increase in postsynaptic conductance. 3. The d-IPSP is produced by a fast-rising increase in postsynaptic membrane conductance that peaks at 10 microS and lasts nearly 100 ms. 4. An 8-ms, 10-mV depolarizing prepulse inactivated 90% of the inward current evoked by a subsequent step to 33 mV above rest potential, which was -70 mV. d-IPSPs having similar amplitudes should have similar effects on the inward current evoked by an excitatory postsynaptic potential (EPSP). 5. The input resistance of MoG decreased by greater than 60% when the cell was depolarized to 11 mV above rest. This resistance change corresponds to delayed rectification, which should also contribute to the increase in input conductance during a d-IPSP. 6. Depolarization of MoG by 10 mV reduced the excitatory postsynaptic current through the GMS by up to 30%. The reduction in synaptic current occurs because postsynaptic depolarization reduces the transynaptic driving force and increases the reverse bias of the electrically rectifying synapse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213132 TI - Operational unit responsible for plane-specific control of eye movement by cerebellar flocculus in cat. AB - 1. Main findings in our previous studies are as follows: 1) there are three Purkinje cell zones running perpendicular to the long axis of the folia in the cat flocculus, 2) the caudal zone controls activity of the superior rectus (SR) and inferior oblique (IO) extraocular muscles via the y-group and oculomotor nucleus (OMN) neurons, and 3) the middle zone controls activity of the lateral (LR) and medial rectus (MR) muscles via the medial vestibular (MV) and abducens nucleus (ABN) neurons. In the present study, the neuronal pathways from the remaining rostral zone were investigated in the anesthetized cat. 2. Target neurons of rostral zone inhibition in the superior vestibular nucleus (SV) were identified by observing cessation of spontaneous discharges after rostral zone stimulation. Efferent projections were studied by the use of systematic microstimulation techniques. Unitary responses to stimulation of the eighth nerves were also investigated. 3. There are two types of the target neurons: 1) those, being located in the central and dorsal parts of the SV, project to the trochlear and oculomotor nuclei innervating superior oblique and inferior rectus muscles via the ipsilateral medial longitudinal fasciculus (MLF); and 2) those, being located along the dorsal border of the SV, project to the contralateral oculomotor nucleus innervating superior rectus and inferior oblique muscles via the extra-MLF route. 4. Both types receive monosynaptic anterior canal nerve input but not posterior canal nerve input. Some neurons receive polysynaptic excitatory input from the contralateral eighth nerve, although commissural inhibition was never observed. 5. From neuronal connections of the rostral and caudal zones and action of the extraocular muscles, it was expected that 1) activity changes of Purkinje cells in the rostral and/or caudal zones on one side resulted in conjugate eye movement in the plane of the anterior canal on the side of the activity changes, 2) cooperative increased activity on both sides resulted in conjugate downward eye movement, and 3) increased activity on one side and decreased activity on the other side resulted in conjugate rotatory eye movement. The rostral and caudal zones may be responsible for eye-movement control in the sagittal plane by cooperative activity changes on both sides and in the transverse plane by reciprocal activity changes on both sides. For eye-movement control in the anterior canal plane, Purkinje cell activity on one side would be sufficient to produce the required movement. In a functional sense, we call the rostral and caudal zones, the vertical-plane zones.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213133 TI - Effects of NH4+ on reflexes in cat spinal cord. AB - 1. In deeply barbiturate-anesthetized animals. NH4+ decreases spinal excitatory synaptic transmission by neuronal depolarization and subsequent block of conduction of action potentials into presynaptic terminals of low-threshold (presumably Ia-) afferents. Because barbiturates by themselves depress excitatory synaptic transmission and may have modified the effects of NH4+, this study examines the effect of NH4+ on excitatory synaptic transmission in the unanesthetized animal. 2. The effects of NH4+ on monosynaptic and polysynaptic excitatory reflexes as well as di- and polysynaptic inhibition were investigated in the spinal cord of the decerebrate and unanesthetized cat in vivo. 3. The monosynaptic excitatory reflex (MSR) elicited by muscle nerve stimulation and polysynaptic excitatory reflexes elicited by muscle (MSR-PSR) or cutaneous nerve stimulation (Cut-PSR) were recorded from the ventral roots L7 or S1. The P-wave was recorded from the cord dorsum. Di- and polysynaptic inhibition was elicited by muscle nerve stimulation and measured as decrease of the MSR. 4. Intravenous infusion of ammonium acetate (AA) decreased MSR and the monosynaptic motoneuron pool excitatory postsynaptic potential (EPSP) recorded from the ventral root (VR EPSP). Decrease of MSR and VR-EPSP was accompanied by an increase of the intraspinal conduction time in presynaptic terminals. The maximal decrease of the MSR was preceded by a period of transient increase of the MSR and reflex discharges from previously subthreshold VR-EPSPs. 5. The effects of NH4+ on MSR and VR-EPSP are consistent with those in barbiturate-anesthetized animals and suggest that NH4+ also decreases monosynaptic excitation in unanesthetized animals by depolarization and subsequent conduction block for action potentials in presynaptic terminals. 6. Decrease of the MSR was accompanied by a decrease of the P-wave, indicating that NH4+ simultaneously decreases mono- and oligosynaptic excitatory synaptic transmission as well as presynaptic inhibition. 7. Decrease of the MSR was accompanied by increases of MSR-PSR and Cut-PSR and decreases of di- and polysynaptic postsynaptic inhibition. 8. The neuronal circuits underlying MSR-PSR and Cut-PSR include presynaptic inhibition of group I and II afferents as well as postsynaptic inhibition of motoneurons. It is suggested that increases of MSR-PSR and Cut-PSR are contributed to by decreases of pre- and postsynaptic inhibition and neuronal depolarization by NH4+. These effects increase afferent input to motoneurons, permit uncontrolled discharge of motoneurons, and initiate reflex discharges by previously subthreshold excitatory postsynaptic potentials. PMID- 2213134 TI - Saccades can be aimed at the spatial location of targets flashed during pursuit. AB - 1. If an eccentric, stationary target is flashed while a subject is performing an eye movement in the dark, can this subject make a saccade to the location in space where the target briefly appeared? Different predictions result from alternative hypotheses regarding the manner in which saccade goals are determined. Retinal error being defined as the vector from the eye position at the time of the flash to the position of the target, the retinal-error hypothesis predicts that the saccade vector will be equal to the retinal-error vector. This hypothesis assumes that the oculomotor system ignores the eye displacement between target presentation and saccade. If so, the target will be missed. In contrast, the spatial-error hypothesis predicts that the eye displacement is taken into account by the brain to calculate the target's physical location to which, therefore, a correct saccade could be aimed. 2. At issue is the generality of a fundamental principle of ocular targeting. Previous studies have established that, if the movement is saccadic, eye displacement is used by the oculomotor system to calculate the target's physical location. In the case of pursuit, perceptual experiments on humans suggest that eye displacement is taken into account although its velocity is underestimated. However, in a recent study McKenzie and Lisberger reported that saccade trajectories starting during pursuit conform to the retinal error hypothesis. In other words, velocity underestimation is close to 100%. 3. Although McKenzie and Lisberger's results are very clear, they might have depended on particular experimental conditions. The issue was reinvestigated in a situation facilitating the discrimination of stimuli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213135 TI - Reciprocal inhibition of soleus motor output in humans during walking and voluntary tonic activity. AB - 1. The extent to which an active, human motoneuron pool can be inhibited via short-latency inhibitory pathways was studied by stimulating the common peroneal nerve and recording the inhibition of on-going soleus electromyographic (EMG) activity. The responses were compared at the same EMG level during walking and tonic voluntary activity to determine whether the inhibition was task dependent. 2. In both tasks the amount of inhibition (measured as the depression in rectified, filtered, and averaged EMG activity) increased approximately linearly with the amount of motor activity, as determined from the mean EMG level before stimulation (correlation coefficient greater than or equal to 0.9). No difference in the amount of inhibition was found between the two tasks at the same stimulus and EMG levels. 3. Previously published studies based on the H-reflex method have reported that the amount of inhibition decreases with the amount of motor activity. On the contrary, single-unit studies and the present results suggest that segmental inhibitory reflexes retain their capacity to mediate a rapid reduction of motoneuronal discharge during voluntary activity. This inhibition may be important in regulating the amount of activity early in the stance phase of walking and during the transition from stance to the swing phase. 4. Analytic results are derived in an APPENDIX that should be of general interest in interpreting the inhibition of motor units from a peristimulus time histogram (PSTH). The linear correlation between inhibition and level of voluntary activity can be explained if newly recruited units are strongly inhibited by the stimulus, whereas previously active motor units are inhibited relatively less, as their firing rate increases with increasing background activity. PMID- 2213136 TI - Alterations in group Ia projections to motoneurons following spinal lesions in humans. AB - 1. The hypothesis that the exaggerated tendon jerks and stretch reflexes that follow chronic spinal cord lesions in humans result from alterations in transmission from group I muscle afferents to motoneurons was tested by making observations on nine normal subjects and 25 patients with spinal cord lesions. All the patients had increased tendon jerks, one-third of them had both increased tendon jerks and increased, velocity-dependent stretch reflexes (i.e.g spasticity). 2. Changes in the firing probability of single, voluntary-activated soleus or tibialis anterior motor units during stimulation of the muscle nerve below the threshold of the alpha-motoneuron axons were used to derive the characteristics of the postsynaptic potentials produced by group I volleys in single motoneurons. Paired stimuli were used to test how multiple volleys in group I muscle afferents were transmitted to motoneurons. 3. Stimulation of the posterior tibial nerve produced a short-latency period of increased firing probability representing the homonymous composite Ia excitatory postsynaptic potential (EPSP) in all soleus motoneurons tested. There was no detectable alteration in the magnitude, duration, or profile of the short-latency facilitation in the patients with spinal lesions when compared with normal subjects. 4. In patients with traumatic spinal cord lesions less than 8 wk in duration the magnitude of the facilitation representing the composite Ia EPSP was significantly larger than normal, although only one out of the four patients in this group had spasticity. 5. In the patients with the greatest spasticity, group I volleys produced a second period of facilitation 11-15 ms after the facilitation representing the composite Ia EPSP. This is presumed to represent enhanced transmission through polysynaptic pathways from group I afferents to motoneurons. 6. In normal subjects the facilitation of motoneurons produced by the second of two group I volleys is greater 5 and 10 ms after the first volley and less 20, 30, and 50 ms after the first volley. These changes involve at least two factors: 1) changes in excitability of peripheral nerves and 2) changes in transmission at the Ia-motoneuron synapse. 7. In patients with spinal lesions the facilitation produced by the second of two muscle-afferent volleys was less depressed at the 30-ms interstimulus interval. 8. Thus two separate abnormalities have been uncovered in human subjects with chronic spinal lesions: 1) a change in the transmission of multiple volleys from muscle afferents to motoneurons and 2) an increase in transmission through polysynaptic pathways from Ia afferents to motoneurons. Both could contribute to the increased tendon jerks and exaggerated stretch reflexes. PMID- 2213137 TI - Computer simulation of group Ia EPSPs using morphologically realistic models of cat alpha-motoneurons. AB - 1. Morphological and electrophysiological data on the electrotonic structure of six triceps surae alpha-motoneurons and on the number and location of 202 Group Ia synapses making contact with ankle extensor motoneurons, previously obtained in this laboratory, were used to construct computer models to examine the generation of composite monosynaptic Group Ia excitatory postsynaptic potentials (EPSPs). 2. A total of 300 active synapses, each generating conductance transients based on voltage-clamp data and having activation times temporally dispersed (range approximately 1.3 ms) according to the conduction velocity profile of Group Ia-afferents, were used to generate composite EPSPs. 3. The shape indexes (foot-to-peak rise times and half widths) of simulated EPSPs matched those of experimentally observed Ia EPSPs reasonably well, although the rise times were, on average, approximately 0.25 ms longer in the simulated EPSPs. This may indicate that the effective temporal dispersion of actual Group Ia monosynaptic EPSPs is less than that the temporal asynchrony used in the simulations. 4. The peak amplitudes of simulated composite EPSPs (6-14 mV), as well as EPSPs produced by single somatic synapses (80-300 microV), were comparable to those found in experimental data. 5. Simulated EPSPs in motoneuron models with two forms of nonuniform Rm distribution ("step" increase from low values of Rm on the soma to much higher but uniform values in the dendrites, versus gradual monotonic "sigmoidal" increases from soma to distal dendrites) were similar in shape and amplitude. This prevented choosing one or the other Rm model as more "correct." 6. Transmembrane voltages at synaptic sites in motoneuron dendrites during generation of composite Ia EPSPs had peak amplitudes less than twice those of the somatic EPSP. The amount of nonlinearity during EPSP production was assessed by making the delivery of synaptic current independent of the local transmembrane voltage. This non-linearity was modest (less than 10%) during composite EPSP generation, consistent with previous experimental evidence. 7. The local voltages produced in various parts of different dendrites during composite EPSP generation depended on the number and location of active synapses and on the electrotonic structure of the particular dendrite. The results show that dendrites that project in different directions away from the motoneuron soma could, in principle, exhibit different degrees of interaction between Ia and other synaptic inputs. 8. Although produced by the same number of active synapses, the simulated composite Ia EPSPs varied over a two-fold range of peak amplitude in relation to motor-unit type, cell input resistance, and cell size (total membrane area).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213139 TI - Reflex activation of muscle spindles in human pretibial muscles during standing. AB - 1. Experiments were performed in standing subjects to determine whether low threshold cutaneous and muscle afferents from mechanoreceptors in the human foot reflexly influence fusimotor neurons innervating pretibial flexor muscles. Recordings were made from 30 identified muscle-spindle afferents, four tendon organ afferents, and one alpha-motor axon innervating the pretibial flexor muscles. The subjects stood without support or vision on a force platform while trains of electrical stimuli (5 stimuli, 300 Hz) were delivered at nonpainful intensities to the sural nerve or to the posterior tibial nerve at the ankle. 2. Seventeen of the 30 spindle endings had no background discharge, and none was activated by the sural or posterior tibial stimuli. Five silent afferents were given a background discharge by sustained pressure on the relevant tendon, but with two the discharge was dominated by a tremor rhythm obscuring any reflex response to the stimuli. Based on peristimulus time histograms (PSTHs), the sural stimuli then produced increases in discharge of two of the remaining three endings at latencies of 84 and 90 ms. These effects could not be explained by muscle stretch and are presumed to have been fusimotor mediated. 3. When the subjects stood freely without support or vision, 13 muscle-spindle endings had a background discharge, but with three endings tremor developed at the ankle and dominated the spindle discharge. Sural stimuli affected the discharge of five of nine endings unaffected by tremor. With three of these endings, there were changes in discharge that could be explained by muscle stretch.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213138 TI - Behavior of human muscle receptors when reliant on proprioceptive feedback during standing. AB - 1. This study investigated the muscle-spindle discharge from the pretibial flexor muscles of standing human subjects while they performed maneuvers that altered their reliance on proprioceptive feedback to control balance. Single-unit recordings were made from 100 identified muscle afferents, 81 from muscle-spindle endings and 19 from Golgi tendon organs. 2. With 49 spindle endings the subjects stood on a horizontal platform and with 32, on a platform tilted in dorsiflexion (4 degrees) to ensure that the pretibial muscles were active to maintain balance. When standing freely on a horizontal platform without support or vision, there was little or no electromyographic (EMG) activity in the pretibial muscles, and spindle discharge rates were low (55% active; mean rate for all 49 endings, 4.1 Hz). When standing similarly on the tilted platform, 69% of the spindle afferents were active, and the mean discharge rate was 5.4 Hz. The greater number of actively discharging spindle afferents and the preservation of mean discharge rate despite muscle shortening indicates that the pretibial muscles are subjected to increased fusimotor drive when they are tonically active to maintain balance. 3. The effects of small degrees of body sway induced voluntarily or by an external stimulus were studied with 41 afferents (29 spindles; 12 tendon organs). Activation of the pretibial muscles to compensate for backward sway was accompanied by a spindle discharge that usually exceeded the discharge produced by comparable passive movement. This indicates that the pretibial muscles are subjected to increased fusimotor drive when they are phasically active to maintain balance. 4. To vary the reliance placed on the feedback from proprioceptive inputs, the subjects abruptly opened and shut their eyes, took and released support, or tilted their heads. There were no detectable changes in afferent activity unless the maneuver produced a change in EMG activity in the pretibial muscles and/or body sway. Thirty afferents (26 of 46 spindles; 4 of 7 tendon organs) underwent a change in discharge rate associated with a transient change in posture, as recorded by the force platform, or a change in EMG activity in the receptor-bearing muscle. The discharge pattern of 23 afferents did not show any clear change with these maneuvers. 5. It is concluded that maneuvers that increase the reliance on proprioceptive feedback when subjects are standing quietly do not significantly alter the fusimotor drive to the pretibial muscles in the absence of muscle contraction.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213140 TI - Interactions between adjacent ganglia bring about the bilaterally alternating differentiation of RAS and CAS neurons in the leech nerve cord. AB - Antibodies to small cardioactive peptide (SCP) label a segmentally iterated subset of cells in the leech nerve cord, including the previously identified alternating SCP (AS) neurons. Unlike the majority of leech neurons, these cells are asymmetrically distributed in the adult nerve cord. Moreover, each AS neuron shows a strong tendency to lie on alternate right and left sides in successive ganglia. Previous work has shown that these unpaired neurons arise from bilaterally paired embryonic homologues, only 1 of which takes on the mature immunoreactive phenotype. The 2 AS homologues within a ganglion compete for this fate, in that either the right or the left homologue will become a mature AS neuron with a high degree of reliability if its contralateral homologue is ablated during embryogenesis. In this paper, we demonstrate the existence of interactions between neurons in adjacent ganglia that could account for the alternation of sides observed during normal development. The unilateral ablation of a single AS homologue neuron forced its contralateral homologue to take on the mature AS fate, and this consistently biased the side of AS development in adjacent, unlesioned ganglia both anterior and posterior to the lesion. One of the AS neurons, the caudal alternating SCP (CAS) cell, was injected with Lucifer yellow in adult nerve cords and was shown to have a large primary axon that extends into more anterior ganglia, as well as other, finer axons that are variable in number and arrangement. If the interganglionic interaction of AS neuron homologues is mediated by their primary axons, signals of developmental import must be transmitted both anterogradely and retrogradely along the axon's length. The present results indicate that the development of individual AS neurons is influenced by homologous cells located in the same and neighboring ganglia and suggest that the final, multisegmental patterning of the AS neuron distribution is not predetermined, but rather, arises as an emergent property of the cell interactions that occur during nervous system differentiation. PMID- 2213141 TI - A circuit for detection of interaural time differences in the brain stem of the barn owl. AB - Detection of interaural time differences underlies azimuthal sound localization in the barn owl Tyto alba. Axons of the cochlear nucleus magnocellularis, and their targets in the binaural nucleus laminaris, form the circuit responsible for encoding these interaural time differences. The nucleus laminaris receives bilateral inputs from the cochlear nucleus magnocellularis such that axons from the ipsilateral cochlear nucleus enter the nucleus laminaris dorsally, while contralateral axons enter from the ventral side. This interdigitating projection to the nucleus laminaris is tonotopic, and the afferents are both sharply tuned and matched in frequency to the neighboring afferents. Recordings of phase-locked spikes in the afferents show an orderly change in the arrival time of the spikes as a function of distance from the point of their entry into the nucleus laminaris. The same range of conduction time (160 mu sec) was found over the 700 mu m depth of the nucleus laminaris for all frequencies examined (4-7.5 kHz) and corresponds to the range of interaural time differences available to the barn owl. The estimated conduction velocity in the axons is low (3-5 m/sec) and may be regulated by short internodal distances (60 mu m) within the nucleus laminaris. Neurons of the nucleus laminaris have large somata and very short dendrites. These cells are frequency selective and phase-lock to both monaural and binaural stimuli. The arrival time of phase-locked spikes in many of these neurons differs between the ipsilateral and contralateral inputs. When this disparity is nullified by imposition of an appropriate interaural time difference, the neurons respond maximally. The number of spikes elicited in response to a favorable interaural time difference is roughly double that elicited by a monaural stimulus. Spike counts for unfavorable interaural time differences fall well below monaural response levels. These findings indicate that the magnocellular afferents work as delay lines, and the laminaris neurons work as co-incidence detectors. The orderly distribution of conduction times, the predictability of favorable interaural time differences from monaural phase responses, and the pattern of the anatomical projection from the nucleus laminaris to the central nucleus of the inferior colliculus suggest that interaural time differences and their phase equivalents are mapped in each frequency band along the dorsoventral axis of the nucleus laminaris. PMID- 2213142 TI - Magnocellular and parvocellular contributions to responses in the middle temporal visual area (MT) of the macaque monkey. AB - Many lines of evidence suggest that the visual signals relayed through the magnocellular and parvocellular subdivisions of the primate dorsal LGN remain largely segregated through several levels of cortical processing. It has been suggested that this segregation persists through to the highest stages of the visual cortex, and that the pronounced differences between the neuronal response properties in the parietal cortex and inferotemporal cortex may be attributed to differential contributions from magnocellular and parvocellular signals. We have examined this hypothesis directly by recording the responses of cortical neurons while selectively blocking responses in the magnocellular or parvocellular layers of the LGN. Responses were recorded from single units or multiunit clusters in the middle temporal visual area (MT), which is part of the pathway leading to parietal cortex and thought to receive primarily magnocellular inputs. Responses in the MT were consistently reduced when the magnocellular subdivision of the LGN was inactivated. The reduction was almost always pronounced and often complete. In contrast, parvocellular block rarely produced striking changes in MT responses and typically had very little effect. Nevertheless, unequivocal parvocellular contributions could be demonstrated for a minority of MT responses. At a few MT sites, responses were recorded while magnocellular and parvocellular blocks were made simultaneously. Responses were essentially eliminated for all these paired blocks. These results provide direct evidence for segregation of magnocellular and parvocellular contributions in the extrastriate visual cortex and support the suggestion that these signals remain largely segregated through the highest levels of cortical processing. PMID- 2213143 TI - The cold stability of microtubules increases during axonal maturation. AB - The development of cold-stable microtubules (MTs) was studied in maturing rat sciatic nerves. From 4 to 10 weeks of age, there was a large increase in the proportion of tubulin associated with stable MTs. A greater fraction of axonal tubulin than nonaxonal tubulin was associated with stable MTs. The labeled tubulin remaining behind the peak of slow axonal transport was more highly associated with stable MTs than tubulin in the peak itself. Immunoassay confirmed that the sciatic nerve contains a pool of stable MTs not identical to the peak of tubulin transport. The developmental increase in MT stability is not associated with any increase in the acetylation of tubulin or with alterations in the major MT-associated proteins. One aspect of maturation of the axonal cytoskeleton may involve deposition of tubulin into stable MTs that are either stationary or moving slowly with regard to the peak of transported tubulin. PMID- 2213144 TI - Inhibition of protein kinase C blocks two components of LTP persistence, leaving initial potentiation intact. AB - Protein kinase C (PKC) activity is increased following hippocampal long-term potentiation (LTP; Akers et al., 1986). A similar increase in PKC activity is measured following the induction of a long-lasting potentiation with abbreviated high-frequency stimulation (HFS) in combination with PKC-activating phorbol esters (Colley et al., 1989). Because phorbol esters have no effect on the initial potentiation produced with HFS, and because PKC activity appears to be related to the persistence of LTP and not to the initial change, we concluded that PKC regulates a post-initiation component of LTP. To define the time domain in which PKC activation is necessary for LTP, we studied the effect of the PKC inhibitors polymyxin B (PMXB) and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) micropressure ejected at different time points before and after the induction of LTP. LTP was produced in intact rats with HFS of the perforant path, and inhibitor ejections were made in the molecular layer of the dentate gyrus. PMXB, which at lower doses is a selective inhibitor of PKC, had no effect on initial potentiation, yet caused decay of the potentiated response to baseline within 2 hr. Decay occurred when PMXB was ejected 15 min before and 15 and 30 min after HFS. PMXB, at either low or high doses, was ineffective in blocking LTP persistence at time points greater than 30 min after HFS. Low doses of H-7 produced similar effects to those of PMXB. However, in contrast to a high dose of PMXB, a high dose of H-7 inhibited the persistence of LTP when delivered 240 min after HFS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213145 TI - Interaction of forskolin with voltage-gated K+ channels in PC12 cells. AB - Forskolin (FSK) directly blocks a distinct class of voltage-dependent K+ channels in pheochromocytoma cells. We have studied the biophysical mechanism of FSK action on these channels. The mean open duration decreased linearly with [FSK], indicating that a single molecule of FSK interacts with a single open K+ channel. FSK did not alter the voltage dependence of activation or the latency to first opening. Whole-cell currents in the presence of FSK did not show a rising phase in tail currents, suggesting that FSK-bound channels can close. We used a kinetic scheme in which FSK binds preferentially to the open state of the channel to describe its interaction with the K+ channel. This scheme is analogous to the modulated receptor hypothesis used to describe the interaction of local anesthetics with voltage-dependent Na+ channels. PMID- 2213147 TI - The recovery of forelimb-placing behavior in rats with neonatal unilateral cortical damage involves the remaining hemisphere. AB - Following unilateral lesions of the somatic sensorimotor cortex (SMC) in neonatal, but not adult, rats, an aberrant ipsilateral corticospinal projection originates from the undamaged hemisphere (Hicks and D'Amato, 1970; Leong and Lund, 1973; Castro, 1975). We have evaluated the contribution of the hemisphere contralateral to a unilateral lesion of the SMC in the recovery of tactile forelimb-placing behavior. Neither adult-lesioned or neonatally lesioned animals show evidence for placing deficits with either forelimb when tested 30 or 42 d after the lesion. However, in adult-lesioned animals, a subsequent lesion of the undamaged SMC on postlesion day 42 produces placing deficits only with the forelimb contralateral to the second lesion, while such a second lesion in the neonatally lesioned rats results in placing deficits with both forelimbs. Anatomical observations in the animals used for behavioral analyses confirm previous reports of a substantial ipsilateral corticospinal projection in rats with unilateral SMC damage as neonates and demonstrate that many of these aberrant fibers recross the midline within the spinal cord to arborize extensively within the ipsilateral spinal gray. These findings indicate that, following unilateral SMC lesions in neonates, the contralateral hemisphere mediates some aspects of the recovery of forelimb placing. The aberrant ipsilateral corticospinal projection may provide the anatomical substrate through which the cortex effects this recovery. PMID- 2213146 TI - Spectral properties of V4 neurons in the macaque. AB - Spectral properties of 129 cells in the V4 area of 5 macaque monkeys were studied quantitatively with narrow-band and broad-band colored lights. The large majority of cells exhibited some degree of wavelength sensitivity within their receptive fields. The half-bandwidth of the primary peak in the spectral-response curve was less than 50 nm for 72% of the cells; the mean half-bandwidth of these cells, 27 nm, is similar to that found for color-opponent ganglion cells and cells in the parvocellular dorsal lateral geniculate nucleus (dLGN). Contrast-response functions indicated that the narrow spectral tuning of these cells derived from cone opponent interactions. From comparison of receptive-field sizes, we suggest that a typical V4 neuron sums inputs that ultimately derive from several thousand ganglion or parvocellular dLGN cells. In spite of their wavelength sensitivity, most V4 cells had properties that would not fit some simple criteria for classification as "color selective." First, few cells showed overt signs of color opponency, namely, on-inhibition or off-excitation to spectrally opponent wavelengths. Second, about 30% of the cells in V4 had spectral-response curves with 2 peaks. (The wavelength distribution of these second peaks was almost identical to that of primary peaks, and combinations of peak wavelengths were fairly random.) Third, most cells responded to white light; overall, the response to white light was about 60% of that to the best narrow-band or broad-band colored light. Similarly, most V4 cells gave at least a small response to all or nearly all of the different broad-band colored lights we presented. Therefore, a given V4 cell is very likely to respond to most of the colored or white surfaces in natural scenes. These combinations of response properties probably explain the widely divergent percentages of "color" cells reported in previous studies of V4. The most unusual spectral property we found in V4 was a large, spectrally sensitive surround outside the "classical receptive field" of most cells. Although stimulation of the surround by itself did not cause any response, surround stimulation could completely suppress the response to even the optimally colored stimulus in the receptive field. In general, the optimal wavelengths for receptive-field excitation and surround suppression were the same or nearly so. Thus, "color contrast" may be computed in V4. In some cases, contrasting wavelengths in the surround caused moderate enhancement of response to a receptive-field stimulus.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213149 TI - Androgyny: a function of degree? AB - Related to the issue of sexism is the concept of psychological androgyny, or the lack of tendency toward masculine or feminine traits. Studies have examined psychological androgyny through administration of the BEM Sex-Role Inventory and the Guilford-Zimmerman Temperament Survey. Whereas one researcher concluded that dental hygiene students are stereotypically feminine, another researcher reported the tendency toward traditionally masculine traits. Both researchers utilized samples consisting solely of baccalaureate students. This paper presents the issue of psychological androgyny, the impact that sex-typing has on the profession of dental hygiene, and the results of a study examining androgyny among dental hygiene students. Three hundred twenty-one first- and second-year dental hygiene students representing four geographic regions within the United States were sampled. The 60-item BEM Sex-Role Inventory was administered to determine the extent of masculinity, femininity, and androgyny within this sample. Comparisons were made by degree program, class status, and geographic location. The authors tested the hypothesis that baccalaureate degree-seeking dental hygiene students were more androgynous than associate degree-seeking dental hygiene students. Data were analyzed by a general linear model for unbalanced designs and chi-square to determine significance. Results indicated that students in all dental hygiene programs are most frequently sex-typed as feminine, with androgyny as the second most frequently sex-typed characteristic. There was a significant difference in psychological androgyny when comparing students by degree program. A greater number of baccalaureate degree-seeking students reflected an androgynous sex-typing. PMID- 2213148 TI - Developmental expression of the 43K and 58K postsynaptic membrane proteins and nicotinic acetylcholine receptors in Torpedo electrocytes. AB - The expression of the postsynaptic 43-kDa and 58-kDa proteins and actin during development of the Torpedo marmorata electric organ was compared to that of nicotinic acetylcholine receptors (AChRs). Western blot analysis demonstrates that AChRs and proteins of 43 kDa (43K protein) and 58 kDa (58K protein) are all present prior to synaptogenesis. Subsequently, levels of all 3 synaptic proteins increase dramatically during differentiation and innervation of electrocytes. In contrast, actin is present in relatively high concentrations at early times and decreases thereafter. The equimolar ratio of AChRs and the 43K protein found in the adult electric organ is established early in development. Furthermore, the AChR and 43K protein share a common postsynaptic localization in electrocytes following synapse formation. Aggregates of the AChR that form at the ventral pole of the oval-shaped electrocytes prior to innervation, however, show no detectable immunofluorescence staining with anti-43K monoclonal antibodies. Therefore, in some cases, aggregation of AChRs occurs without the 43K protein. PMID- 2213150 TI - A comprehensive approach to teaching management in a degree-completion dental hygiene program. AB - Changes in society have dictated changes in the future of the dental hygiene profession and in the curriculum used to prepare students. Dental hygiene students should be prepared to assume a variety of new roles in the oral health and health care fields, including administrator/manager, researcher, educator, clinician, patient advocate, and change agent. The role of the administrator/manager had been identified as an important one for dental hygienists. In order to develop the skills necessary to obtain a position in management or administration, dental hygiene students should have educational preparation in these areas. This paper describes the development of an enhanced business curriculum in a degree-completion program. The curriculum provides a basic foundation for the development of effective management skills and includes courses in business, human resources management, and marketing, along with elective course offerings and an externship program. An integrated approach to management is employed, with emphasis on application to oral health and health care delivery systems. PMID- 2213152 TI - The economics of dental hygiene work in traditional and nontraditional settings. AB - The information presented in this paper was obtained as part of an ongoing longitudinal study of 1982 dental hygiene graduates. This portion of the study was contracted by the American Dental Hygienists' Association and provides information about method and amount of remuneration, fringe benefits, pay increases, and amount of money generated from dental hygienists' services. Data presented here were collected at two points in time: September 1985 and September 1986. The September 1985 survey was returned by 850 dental hygienists (83%) and the September 1986 survey was completed by 766 subjects (77%). Data were analyzed for clinical dental hygienists working in traditional and nontraditional settings. Results showed that most dental hygienists were salaried (80% traditional, 100% nontraditional) with a 1985 mean annual income of $19,160 for traditional and $17,197 for nontraditional hygienists. The mean daily wage in 1986 was $106.27 for traditional and $85.12 for nontraditional hygienists. Nontraditional hygienists were more likely to have received a pay increase in the previous six months and to receive fringe benefits than were traditional hygienists. Wages earned and money generated from dental hygiene services varied greatly. On the average, hygienists' wages constituted about one-third of the fees their services generated. PMID- 2213151 TI - An evaluation of computer-based instruction versus printed study guides in a dental material course. AB - Although dental and allied dental educators increasingly use computer-based instruction (CBI), few studies have reported on its effectiveness. A study was designed to compare the effectiveness of CBI study guides with that of printed study guides in a dental materials course taught using Keller's Personalized System of Instruction (PSI). To evaluate the effectiveness of CBI versus printed study guides, student performance on unit mastery tests was assessed by means of chi-square analyses. Overall, it was found that students using CBI study guides did not pass significantly more unit tests than those using printed study guides. It was found, however, that high-aptitude students using CBI study guides performed significantly better than high-aptitude students using printed study guides. Students gave high ratings to both printed and CBI study guides. PMID- 2213154 TI - A surgeon's risk of AIDS. AB - A probabilistic model is used to estimate the cumulative risk to surgeons from human immunodeficiency virus (HIV). Recent data suggest that the probability of infection following percutaneous inoculation is about 1 in 250 cases. Several studies suggest that the frequency of percutaneous injury in surgery is at least 1 in 40 cases, for some as high as 1 in 20 cases. Assuming that on the average a surgeon will perform 350 operations per year and will practice for 30 years, the cumulative risk of HIV infection will depend on the prevalence of HIV infection in the surgical population. For HIV prevalences of 1 in 100 to 1 in 10, the cumulative risk per surgeon ranges from 1 in 100 to 1 in 5, respectively. Based on these risk estimates, it is crucial to decrease the frequency of percutaneous injury. The case is made for substantial improvements in barrier protection and modification of surgical technique. PMID- 2213153 TI - Dental hygiene licensure specifications on pain control procedures. AB - State boards of dentistry of the 51 licensure jurisdictions and 51 constituent hygiene presidents were sent identical surveys to obtain current information about dental hygiene licensure specifications for nitrous oxide analgesia, and infiltration, block, and topical anesthesia. The response rate was 72% (N = 37) from boards and 90% (N = 46) from constituent presidents. Results showed that western states are more likely to allow delegation of pain control functions. Of the four functions, topical anesthesia is the most and nitrous oxide analgesia is the least delegated. Most states that allow delegation of pain control procedures did so in the 1970s and 1980s. A majority of states where pain control functions are legal specify direct or indirect supervision and certification through board approved courses. Percentages of hygienists certified in functions ranged from a low of 0% to a high of 100%. Boards and presidents agreed closely on functions allowed, certification requirements, and year of legalization. Agreement was lower on the type of supervision required for all procedures except nitrous oxide analgesia. No reports of patient reactions to or formal complaints about pain control procedures provided by hygienists were known to state boards or constituent presidents. PMID- 2213155 TI - Surgical management of exophytic chiasmatic-hypothalamic tumors of childhood. AB - Sixteen children underwent 18 operations for radical resection of chiasmatic hypothalamic tumors. The clinical presentation correlated with age: infants under 1 year of age presented with macrocephaly, failure to thrive, and severe visual failure; children aged 1 to 5 years predominantly had precocious puberty with mild visual deficits; and older children (greater than 5 years old) had slowly progressive loss of vision. All three infants had biologically aggressive tumors in spite of low-grade histology, and died from progressive tumor growth. Eleven of the 13 children aged 1 year or over are alive and well, without clinical or radiographic evidence of disease progression, 4 months to 4 1/2 years following surgery. Six of these patients, with a follow-up period of 10 months to 4 1/2 years (mean 27 months), have had no adjuvant therapy following radical surgical resection. The authors conclude that: 1) radical surgical resection of chiasmatic hypothalamic tumors can be performed with minimal morbidity; 2) radical resection may delay the time to disease progression in older children and postpone the need for irradiation; 3) resection of postirradiation recurrent tumors may provide neurological improvement and long-lasting clinical remission; and 4) chiasmatic hypothalamic tumors of infancy are aggressive neoplasms that require multimodality therapy. PMID- 2213156 TI - Zygomatic approach to skull-base lesions. AB - A modification of the preauricular skull-base approach is described. After sectioning and downward displacement of the zygomatic arch, the coronoid process of the mandible is dissected and sectioned at its base. The temporal muscle, with its coronoid insertion, is then retracted upward. This approach provides direct and unobstructed access to the temporal and infratemporal fossae. Adequate vascularity of the temporal muscle is maintained. The exposure encompasses the internal carotid artery in the neck for vascular control. Extensive reconstruction is eliminated. The described technique was used in seven patients with lesions of the skull base. There was no operative mortality, and morbidity consisted of temporary restriction of mandibular opening in two patients. PMID- 2213157 TI - Surgical treatment of thyrotropin-secreting pituitary adenomas. AB - Thyrotropin-secreting pituitary adenomas have been diagnosed more frequently as radiographic techniques and biochemical assays have improved; however, they remain uncommon and are unfamiliar to most neurosurgeons. This report concerns eight patients with hyperthyroidism, inappropriately elevated levels of serum thyrotropin and alpha-subunit, and radiographic evidence of pituitary tumor. All underwent surgery and had pathological confirmation of a thyrotropin-secreting adenoma, and most had been subjected to prior ablation of the thyroid gland. Only one tumor was a microadenoma; the others ranged in size from 1.4 to 12 cm, and invasion of parasellar structures was common. Thyrotropin, triiodothyronine, thyroxine, and alpha-subunit were measured preoperatively and at intervals postoperatively. Coexistent hormonal abnormalities (which occurred in all patients) included acromegaly and hyperprolactinemia and were also monitored. All four patients who had tumors less than 2 cm in diameter remain alive. Complete extirpation of tumor in these patients produced rapid correction of all hormonal abnormalities and resolution of clinical hyperthyroidism. The other four patients had larger invasive tumors: two died soon after surgery, one died of disseminated tumor 8 years after presentation, and one remains alive with residual tumor. Tumors secreting thyroid-stimulating hormone are less easily cured by surgery than are other types of pituitary adenoma because of the large size and invasive features that many attain during the delay to diagnosis; medical therapy can subdue the tumor but not cure it. The experience with these patients establishes the importance of early diagnosis and surgical excision for successful treatment, and demonstrates the utility of modern diagnostic techniques for finding these lesions. As occurs in Nelson's syndrome after adrenalectomy for Cushing's disease, ablation of the target organ may allow the tumor to convert to a more clinically malignant form which is resistant to cure. PMID- 2213158 TI - Initial CT findings in 753 patients with severe head injury. A report from the NIH Traumatic Coma Data Bank. AB - In this prospective multicenter study, the authors have examined data derived from the initial computerized tomography (CT) scans of 753 patients with severe head injury. When the CT findings were related to abnormal intracranial pressure and to death, the most important characteristics of the scans were: midline shift: compression or obliteration of the mesencephalic cisterns: and the presence of subarachnoid blood. Diffuse hemispheric swelling was also found to be associated with an early episode of either hypoxia or hypotension. PMID- 2213159 TI - Neurobehavioral outcome 1 year after severe head injury. Experience of the Traumatic Coma Data Bank. AB - The outcome 1 year after they had sustained a severe head injury was investigated in patients who were admitted to the neurosurgery service at one of four centers participating in the Traumatic Coma Data Bank (TCDB). Of 300 eligible survivors, the quality of recovery 1 year after injury was assessed by at least the Glasgow Outcome Scale (GOS) in 263 patients (87%), whereas complete neuropsychological assessment was performed in 127 (42%) of the eligible survivors. The capacity of the patients to undergo neuropsychological testing 1 year after injury was a criterion of recovery as reflected by a significant relationship to neurological indices of acute injury and the GOS score at the time of hospital discharge. The neurobehavioral data at 1 year after injury were generally comparable across the four samples of patients and characterized by impairment of memory and slowed information processing. In contrast, language and visuospatial ability recovered to within the normal range. The lowest postresuscitation Glasgow Coma Scale (GCS) score and pupillary reactivity were predictive of the 1-year GOS score and neuropsychological performance. The lowest GCS score was especially predictive of neuropsychological performance 1 year postinjury in patients who had at least one nonreactive pupil following resuscitation. Notwithstanding limitations related to the scope of the TCDB and attrition in follow-up material, the results indicate a characteristic pattern of neurobehavioral recovery from severe head injury and encourage the use of neurobehavioral outcome measurements in clinical trials to evaluate interventions for head-injured patients. PMID- 2213160 TI - Monosomy 22 in rhabdoid or atypical tumors of the brain. AB - Cytogenetic studies of three rare childhood brain tumors were performed. Two children presented with pure rhabdoid tumors. The third child had a tumor composed of a mixture of rhabdoid elements with neuroepithelial, epithelial, and mesenchymal tissue - an atypical teratoid tumor. All three tumors demonstrated monosomy 22 as the only cytogenetic abnormality. The cytogenetic findings suggest that loss of a gene or genes on chromosome 22 may be involved in the initiation or progression of these malignant tumors. Further studies on additional fresh tumor specimens are warranted; however, it is possible that cytogenetic studies may be used as an additional means of diagnosing rhabdoid or atypical teratoid tumors of the brain. PMID- 2213161 TI - Meningiomas mimicking cerebral schwannoma. AB - A brain tumor with histological features reminiscent of schwannoma with underlying meningioangiomatosis was subjected to electron microscopic and immunohistochemical analysis, which confirmed the neoplasm as a meningioma. This prompted reexamination of a similar tumor, described in a previous publication as a cerebral schwannoma, with identical immunohistochemical techniques. The results obtained favored alteration of this diagnosis to that of meningioma. This experience has led the authors to recommend the use of immunohistochemistry techniques when evaluating unusual intracranial neoplasms. PMID- 2213162 TI - Use of CT and MR imaging to distinguish intracranial lesions and to define the need for biopsy in AIDS patients. AB - To explore the potential usefulness of imaging studies in the diagnosis of focal central nervous system (CNS) lesions associated with acquired immunodeficiency syndrome (AIDS), the authors retrospectively examined the radiographic studies of 149 AIDS patients who presented with signs and symptoms of the three most common focal CNS lesions. Of these patients, 74 (50%) had Toxoplasma abscesses, 45 (30%) had primary CNS lymphoma, and 30 patients (20%) had progressive multifocal leukoencephalopathy (PML). Magnetic resonance (MR) imaging was more sensitive than computerized tomography (CT) in detecting lesions, especially in cases of PML. Whereas CT was unable to distinguish mass lesions caused by toxoplasmosis from those caused by lymphoma, 71% of the solitary lesions seen on MR images were lymphomas. These results indicate that empirical treatment for toxoplasmosis, the most common initial treatment for AIDS patients with neurological symptoms stemming from mass lesions, is not likely to be successful for patients with solitary lesions on MR images. Rather, early biopsy is advisable. If the presence of lymphoma is confirmed, the rapid initiation of treatment can allow prolonged high-quality survival. PMID- 2213163 TI - Clonal origin of pituitary adenomas. AB - Benign pituitary adenomas are among the most common neurosurgical tumors and account for a diversity of clinical syndromes due to their hormone content and release. To determine whether these tumors arise from a single cell or multiple cells, the authors studied X chromosome inactivation in deoxyribonucleic acid (DNA) isolated from pituitary adenomas in women. Tumors of three different hormonal subtypes were examined. One tumor contained cells immunoreactive for prolactin and human growth hormone; one tumor contained foci immunoreactive for the beta-subunits of luteinizing hormone and follicle-stimulating hormone; and the third tumor had no immunoreactive prolactin, human growth hormone, beta subunits of thyroid-stimulating hormone, luteinizing hormone, or follicle stimulating hormone, or the alpha-subunit. Analysis of the DNA revealed that, in each of the three pituitary tumors, one X chromosome was active in all cells and one X chromosome was inactive, indicating that each of these tumors was monoclonal in origin. It is concluded that clinically evident pituitary tumors arise from a genetic mutation in a single cell. PMID- 2213164 TI - Hormonal dependency of cerebral meningiomas. Part 1: Female sex steroid receptors and their significance as specific markers for adjuvant medical therapy. AB - Female sex steroid receptors were examined in 50 human cerebral meningiomas. For estrogen receptors, high-affinity binding sites (dissociation constant (Kd): 0.05 to 0.2 nM) were found in the cytosolic fraction with a capacity of less than 4 fmol/mg protein in 10 meningiomas using a dextran-coated charcoal (DCC) assay. In the same cytosolic fraction, the solid-phase enzyme immunoassay revealed only one cytosol with a positive colorimetric reaction equal to 5 fmol/mg protein. However, in the nuclear compartment, none of the tumors stained positively for estrogen receptors with immunohistochemical techniques. In addition, the most convincing evidence for the absence of estrogen receptors was obtained by in situ hybridization using an oligonucleotide probe complementary to a fraction of the human receptor messenger ribonucleic acid (mRNA). In none of the 50 meningiomas was the expression of estrogen mRNA coding for the estrogen receptor detected. For progesterone receptors, high-affinity binding sites (Kd: 0.3 to 2.6 nM) were found in 49 of the 50 tumors using a DCC assay. In the same cytosols, solid-phase enzyme immunoassay revealed that each tumor was positive for progesterone receptors. However, in the nuclear compartment, only five tumors had partially positive staining for progesterone receptors with immunohistochemical techniques. Within the confines of this study, it is concluded that: 1) the estrogen receptor is generally absent in meningioma tissue, and 2) the progesterone receptor is mainly absent in the nuclear compartment, leading to the conclusion that the cytosolic progesterone receptor may be an inactive form. This study suggests that female sex steroid receptors are not primarily involved in the proliferative rate of cerebral meningiomas and that they are of no current significance as markers for adjuvant medical therapy of most meningiomas. PMID- 2213165 TI - Hormonal dependency of cerebral meningiomas. Part 2: In vitro effect of steroids, bromocriptine, and epidermal growth factor on growth of meningiomas. AB - Cell culture and biochemical techniques have been employed to examine the effects of steroids, bromocriptine, and epidermal growth factor (EGF) on the growth and proliferative potential of meningiomas. In cell culture, the growth of meningiomas was not altered by progestogens, antiprogestogens, or 17beta estradiol. The progestogen, norethisterone, had no effect on the uptake by meningiomas cell cultures of 3H-thymidine. Furthermore, cytosolic deoxyribonucleic acid (DNA) polymerase activity of meningiomas did not correlate with the progesterone receptor status of the same tumors. In contrast, the androgen antagonists, cyproterone acetate and 11-alpha-hydroxyprogesterone, and the dopamine agonist, bromocriptine, all inhibited the in vitro growth of meningioma cells. The growth of meningioma cell cultures was stimulated by EGF, and there was a positive correlation between the EGF content and DNA polymerase activity in meningioma cytosols. These results demonstrate that female sex steroids do not influence growth of meningiomas in vitro, whereas antiandrogens and bromocriptine have an antiproliferative effect. Consequently, bromocriptine and antiandrogens may have a role in the medical treatment of meningiomas. In addition, these results suggest that EGF may be involved in the genesis and/or progression of meningiomas. PMID- 2213166 TI - Intracarotid hydroxyethyl methacrylate solution causing stroke in dogs. AB - Hydroxyethyl methacrylate (HEMA) has been advocated as a polymerizing solution with which to prevent deflation of detachable balloons in interventional neuroradiology. It is pertinent to know if unpolymerized HEMA would have untoward effects if accidentally released into the carotid artery by balloon rupture or deflation. Seven mongrel dogs underwent transfemoral catheterization of the common carotid artery and subsequent injection of HEMA solution in volumes of 1 cc in five dogs, 2 cc in one, and 4 cc in one. Angiography performed at the time of injection revealed evidence of intravascular thrombosis as well as possible spasm. Three surviving animals were sacrificed at 48 hours; the brains were fixed and examined histopathologically. One brain was normal and one was autolyzed and could not be examined. Five of the seven animals had histopathologically documented cerebral infarctions of varying size. No foreign substance was seen within the blood vessels to suggest intravascular polymerization. The animals injected with 2 or 4 cc HEMA solution did not survive 48 hours. Literature review reveals little documentation of the toxicology of intravascular HEMA. With its increasing popularity as a compound for polymerization in detachable balloons introduced into the brain, further investigations are warranted to understand the physical properties of the compound and potential risks of its use. PMID- 2213167 TI - Spinal cord arteriovenous malformation with an associated lymphatic anomaly. Case report. AB - Spinal cord arteriovenous malformations (AVM's), like other vascular anomalies of the central nervous system, can be associated with similar vascular lesions of the skin and viscera. A 7-year-old girl, who presented with rapidly progressing paraplegia, was found to have a spinal cord AVM, cutaneous angioma, and a chylous malformation of the lymphatic system. She had previously undergone treatment for a posterior thoracic cutaneous angioma. At surgery, upon incision of the paravertebral muscle fascia, viscous pale fluid was encountered emanating from a foramen in the thoracic lamina. The spinal AVM was resected in spite of concern that the abnormality represented spinal osteomyelitis. Postoperatively, there was full return of function in the lower extremities, along with recurrent episodes of chylothorax, which slowly came under control with dietary manipulation. A review of the anatomy of the thoracic duct and nontraumatic causes of chylothorax is presented, and the association of cutaneous and central angiomas is discussed. Finally, the treatment of chylothorax is delineated. PMID- 2213168 TI - Hemiparkinsonism as a complication of an Ommaya reservoir. Case report. AB - The authors describe the case of a 28-year-old woman who developed the following symptoms in her right hand: a lasting resting tremor, transient focal rigidity, and paresthesia. These deficits occurred following treatment with intrathecal methotrexate via an Ommaya reservoir which was placed too deeply, resulting in trauma to the contralateral mesencephalon. PMID- 2213169 TI - Fourth ventricular schwannoma. Case report. AB - A schwannoma arising from the dorsum of the pontomedullary junction and presenting as an exophytic mass in the fourth ventricle is described. A ventricular schwannoma has not previously been reported in the literature. The presenting clinical and radiographic features and the pathology of this tumor are summarized, and an explanation is sought for its unusual location. PMID- 2213170 TI - Myxomatous cyst of the brachial plexus. Case report. AB - The case of a myxomatous cyst of the brachial plexus is presented. The clinical course is reported, and the frequency of the lesion, diagnostic workup, histopathology, and surgical therapy are discussed. PMID- 2213172 TI - Intradural epithelial cyst at the craniovertebral junction. Case report. AB - A case of an intradural epithelial cyst at the craniovertebral junction is reported in a 37-year-old man. The classification of these rare lesions is discussed. PMID- 2213171 TI - Postlaminectomy ossified extradural pseudocyst. Case report. AB - A large ossified spurious meningocele accompanied by recurrent lumbar disc herniation occurred 7 years after posterior intervention for laminectomy and discectomy in a 53-year-old man. The cyst wall, histologically composed of mature bone tissue, was sparsely covered with connective tissue and lined with fibrocyte or fibroblast-like cells on the inside. The ossified pseudocyst was presumed to have originated from a minute defect in the dura mater which occurred at the time of the first operation. PMID- 2213173 TI - Stereotactic investigation of limbic epilepsy using a multimodal image analysis system. Technical note. AB - A methodology has been developed for stereotactic investigation of limbic epilepsy using an image-analysis system that simultaneously displays different structural and functional images of the brain. The validity and accuracy of this system were established with phantom studies. Surgical planning and electrode implantation are guided by stereotactic magnetic resonance imaging, digital subtraction angiography, and position emission tomography. This methodology provides the spatiotemporal relationship of cerebral structure and function necessary to identify seizure onset and propagation in human limbic system epilepsy. PMID- 2213174 TI - A simple technique of posterior wiring in traumatic instability of the mid to lower cervical spine. Technical note. AB - Wiring without bone fusion in the treatment of traumatic cervical instability is an uncommon procedure. The authors describe a semirigid wiring technique for stabilizing the acute injured movement segment in the mid and lower cervical spine. Results are briefly discussed. PMID- 2213175 TI - Percutaneous microcompression for trigeminal neuralgia. PMID- 2213176 TI - Hyperosmotic blood-brain barrier disruption. PMID- 2213177 TI - One-stage posterolateral decompression and fusion. PMID- 2213178 TI - "Spat-apoplexie". PMID- 2213179 TI - Highlights of the 1990 EANM (European Association of Nuclear Medicine) Congress. PMID- 2213180 TI - Disturbances in the cerebral perfusion of human immune deficiency virus-1 seropositive asymptomatic subjects: a quantitative tomography study of 18 cases. AB - Quantitative measurements of cerebral blood flow (CBF) by xenon-133 (133Xe) tomography, together with magnetic resonance imaging (MRI), electroencephalography (EEG), psychometric tests, and laboratory analyses were performed on 18 human immunodeficiency virus 1 (HIV-1) seropositive asymptomatic subjects. Abnormalities of cerebral perfusion were observed in 16 cases (88%). These abnormalities were particularly frequent in the frontal regions (77% of cases). MRI demonstrated leucoencephalopathy in only two cases. EEG showed only induced diffuse abnormalities in two cases. Psychometric tests showed restricted moderate disturbances in 55% of patients. These disturbances mostly concerned those sectors involved in cognitive functions and memorization. These results indicate that quantitative measurements of CBF by 133Xe-SPECT is capable of detecting abnormalities of cerebral perfusion at a very early stage (Phase II) of HIV-1 infection. These abnormalities are indications of disturbances resulting from unidentified metabolic or vascular lesions. This technique appears to be superior to MRI at this stage of the disease's development. It could provide objective information leading to earlier treatment, and prove useful in evaluating potential antiviral chemotherapy. PMID- 2213181 TI - Tracer kinetics of 15-(ortho-123/131I-phenyl)-pentadecanoic acid (oPPA) and 15 (para-123/131I-phenyl)-pentadecanoic acid (pPPA) in animals and man. AB - The human myocardium retains oPPA as opposed to pPPA. Therefore turnover of oPPA was compared with that of pPPA in rat hearts and in man, the latter by using substrates double-labeled with 123/131I and 14C. Moreover, substrate binding to coenzyme-A was tested in vitro. In rats, oPPA remained mainly in the pool of free fatty acids, as opposed to pPPA, which was metabolized by mitochondrial beta oxidation. Binding to coenzyme-A at maximum was 62% for oPPA, 81% for pPPA and 90% for palmitic acid. In man, after i.v. and intracoronary injection of double labeled oPPA, the two radionuclides reappeared together in venous blood and in coronary sinus respectively, in an unchanged ratio but at a significantly lower rate than with pPPA. It can be concluded that oPPA is bound to coenzyme-A and is retained in the cytosolic lipid pool, while pPPA is metabolized by mitochondrial beta-oxidation. A dual-tracer application of oPPA and pPPA has the potential of being a specific probe for the function of the carnitine shuttle. PMID- 2213182 TI - Significance of fill-in after thallium-201 reinjection following delayed imaging: comparison with regional wall motion and angiographic findings. AB - To identify reversible defects, reinjection of a small amount of thallium-201 (201Tl) following 3-hr delayed imaging was performed in 60 patients with coronary artery disease who had perfusion abnormalities on their post-exercise 201Tl images. Thallium-201 uptake was visually scored and judged as normal (Group 1), reversible defect (Group II), new fill-in after reinjection (Group IIIa) and no fill-in even after reinjection (Group IIIb). New fill-in after reinjection was observed in 27 segments of the 85 segments (32%), showing persistent defect on the stress and delayed images. The wall motion in Group IIIa was worse than Group II but better than Group IIIb. Group IIIa showed Q-wave on ECG more often (69%) than Group II (27%) (p less than 0.01), but less often than Group IIIb (85%) (p less than 0.05). These data indicate that the reinjection 201Tl imaging often identifies new fill-in in the areas of no redistribution on the delayed images and it may hold promise for assessing tissue viability which the conventional imaging may underestimate. PMID- 2213183 TI - Rest reinjection of thallium-201 after redistribution imaging: new questions, old solution. PMID- 2213184 TI - Lymphocele: the spectrum of scintigraphic findings in lymphoceles associated with renal transplant. AB - Lymphocele is a well recognized complication of renal transplant surgery. We performed a retrospective review of 305 renal transplant patients with over 2,500 scintigraphic exams to describe the pattern of activity on technetium-99m-DTPA blood flow and dynamic imaging, and iodine-131-OIH studies. Diagnostic criteria for a lymphocele were ultrasonic evidence of a perirenal fluid collection and analysis of that fluid that demonstrated BUN, creatinine, and electrolytes similar to the patient's plasma. Scintigraphic findings were attributed to a lymphocele if abnormalities were in the same area as the ultrasound fluid collection. Scintigraphic findings attributable to lymphocele resolved in all patients following surgical drainage or peritoneal window placement. Six of the 11 documented lymphoceles demonstrated a cold defect on initial dynamic images that "filled in" to equal background activity and another exceeded background. Three cases showed a rim of increased activity surrounding the lymphocele ("rim sign"). PMID- 2213185 TI - A new myocardial imaging agent: synthesis, characterization, and biodistribution of gallium-68-BAT-TECH. AB - In order to develop a new myocardial perfusion agent for positron emission tomography (PET), a new lipid-soluble gallium complex was evaluated. Synthesis, radiolabeling, characterization, and biodistribution of a unique gallium complex, [67Ga]BAT-TECH (bis-aminoethanethiol-tetraethyl-cyclohexyl), are described. The complex formation between Ga+3 and BAT-TECH ligand is simple, rapid, and of high yield (greater than or equal to 95%). This process is amenable to kit formulation. The complex has a net charge of +1 and a Ga/ligand ratio of 1:1. Biodistribution in rats shows high uptake in the heart as well as in the liver. When [68Ga] BAT-TECH was injected into a monkey, the heart and liver are clearly delineated by PET imaging, suggesting that this complex may be a possible tracer for myocardial perfusion imaging. PMID- 2213186 TI - The potential for generator-based PET perfusion tracers. PMID- 2213187 TI - Effect of mitochondrial and plasma membrane potentials on accumulation of hexakis (2-methoxyisobutylisonitrile) technetium(I) in cultured mouse fibroblasts. AB - Hexakis(2-methoxyisobutylisonitrile) technetium(I) (Tc-MIBI) is representative of a class of 99mTc-based lipophilic cationic myocardial perfusion imaging agents. To test the hypothesis that the mechanism of cellular uptake may involve distribution across biologic membranes in response to membrane potential, Tc-MIBI net uptake and retention were determined in cultured mouse BALB/c 3T3, NIH 3T3, and v-src transformed NIH 3T3 fibroblasts as well as in cultured chick embryo heart cells. Isovolumic depolarization of plasma membrane potentials with 130 mM K 20 mM Cl buffer decreased Tc-MIBI net cell uptake in all preparations. In BALB/c 3T3 cells, depolarizing mitochondrial membrane potential with valinomycin in high K buffer or with the protonophore CCCP inhibited net uptake and retention of Tc-MIBI while hyperpolarizing mitochondrial and plasma membrane potentials with the K+/H+ exchanger nigericin increased Tc-MIBI net uptake. These results indicated that net cellular uptake and retention of Tc-MIBI in fibroblasts were determined by both mitochondrial and plasma membrane potentials; the gamma emitting properties of Tc-MIBI may therefore raise the possibility of monitoring membrane potential in vivo. PMID- 2213188 TI - N-[18F]fluoroacetyl-D-glucosamine: a potential agent for cancer diagnosis. AB - Positron labeled substrates such as sugars, amino acids, and nucleosides have been investigated for the in-vivo evaluation of biochemical processes in cancerous tissue. Hexosamines are obligatory structural components of many biologically important macromolecules, including membrane glycoproteins and mucopolysaccharide. We evaluated a new synthesized pharmaceutical, N [18F]fluoroacetyl-D-glucosamine (18F-FAG), which is a structural analog of N acetyl-D-glucosamine. C3H/HeMsNRS mice bearing spontaneous hepatomas were used for the tissue distribution study. At 60 min after injection, high uptakes were found in tumor (5.16, mean value of %dose/g), liver (3.71), and kidney (3.27). The tumor uptake of 18F-FAG showed the highest value in all tissue. In the PET study, VX-2 carcinoma of the rabbit was clearly visualized. Our preliminary results suggest that 18F-FAG has potential as a new agent for tumor imaging. PMID- 2213189 TI - The current and future use of tumor-localizing agents. PMID- 2213190 TI - Investigation of physicochemical and in-vivo behavior of diastereomeric iron-59, gallium-68, and indium-111-EHPG trivalent metal complexes. AB - EHPG (N, N'-ethylenebis-[2-(o-hydroxyphenyl)glycine]) trivalent metal complexes show diagnostic potential both in radiopharmaceutical applications (gallium-68, indium-111) and as MRI contrast agents (iron). Although several publications report similar behavior of iron, gallium and indium complexes, we observe significant differences between EHPG complexes of these metals both in physicochemical and in vivo analyses. In addition, stereospecific behavior has been observed for the two diastereomers of EHPG when complexed with each metal. Complexes of Fe[59Fe], 68Ga, and 111In with meso, racemic, and unseparated EHPG have been evaluated. Relative lipophilicity has been measured with HPLC. Blood clearance and liver uptake have been correlated with pM values, stability constants and metal ion reduction potentials. PMID- 2213191 TI - Perivesicle pheochromocytoma: the role of iodine-131-MIBG imaging. PMID- 2213192 TI - Tomography using a rotating slant-hole collimator and a large number of projections. AB - A tomographic method using a limited-view angle has been evaluated. In studies using a gamma camera and a rotating 30-degree slant-hole (RSH) collimator, 64 projection images were registered. A special filtered backprojection technique was used for reconstruction of section images parallel to the collimator face. Resolution within such sections was 0.6 cm, 3 cm from the collimator face and 1.3 cm at 18 cm. Depth resolution was 2.2 cm at 3 cm and 5.1 cm at 18 cm. Spacing between section images was regular and geometric distortion negligible. Short axis section images of a myocardium in vivo were qualitatively comparable or better than those obtained with single-photon emission computed tomography. Degradation in the posterior wall due to attenuation and scatter was less. Section images of the facial bones and a hip joint further demonstrated the tomographic capability of the method. PMID- 2213193 TI - Thallium-201 myocardial tomography with a rotating slant-hole collimator and a large number of projections. AB - Tomographic imaging of the myocardium was performed using a gamma camera and a 30 degree rotating slant-hole collimator to register 64 projections from a restricted-view angle. Section images were reconstructed with a two-dimensional filtered backprojection technique. Performance in terms of resolution, effects of misalignment, and three-dimensional activity distribution was evaluated in phantom studies. In a limited clinical study, ten consecutive patients were imaged both with single-photon emission computed tomography (SPECT) and the method described. In the new method, the camera was orientated in the 30 degrees left anterior oblique position with 15 degrees cranial tilt. Due to the short distance from the myocardium to the camera, resolution within reconstructed section images was high, the noise level was comparatively low, and the mean activity level in the posterior wall was significantly higher (p less than 0.005) than in SPECT. PMID- 2213194 TI - Limited-angle tomography for the nineties. PMID- 2213195 TI - Maximum-likelihood estimation: a mathematical model for quantitation in nuclear medicine. AB - In a stimulation study, we investigated the limitations of quantitation in nuclear medicine using a maximum-likelihood (ML) estimation model. We estimated activity, size, and position of a disk-shaped object on a circular, uniform background of unknown activity. The parameter estimates were unbiased, and their standard error was proportional to the square root of the total image counts. The estimates of object activity and size were strongly (negatively) correlated; the position estimates, however, were not correlated with estimates of any other parameters. This implies that a priori knowledge of object location does not improve precision. The minimal model of quantitation tasks should incorporate unknown object activity and size as well as unknown background activity. The ML estimation procedure was used to investigate the trade-off between resolution and sensitivity in gamma camera collimator design. The results implied that for complex tasks such as the multiparameter estimation task investigated here, optimum performance is achieved at a better resolution than that previously found optimal for detection of a well-specified object in a known background. PMID- 2213197 TI - The principal axes transformation--a method for image registration. AB - We have developed a computational technique suitable for registration of sets of image data covering the whole brain volume which are translated and rotated with respect to one another. The same computational method may be used to register pairs of tomographic brain images which are rotated and translated in the transverse section plane. The technique is based on the classical theory of rigid bodies, employing as its basis the principal axes transformation. The performance of the method was studied by simulation and with image data from PET, XCT, and MRI. It was found that random errors in determining the brain contour are well tolerated. Progressively coarser axial sampling of data sets led to some degradation, but acceptable performance was obtained with axial sampling distances up to 10 mm. Given adequate digital sampling of the object volume, we conclude that registration by the principal axes transformation can be accomplished with typical errors in the range of approximately 1 mm. The advantages of the technique are simplicity and speed of computation. PMID- 2213196 TI - Temporal behavior of peripheral organ distribution volume in mammillary systems. II. Application to background correction in separate glomerular filtration rate estimation in man. AB - An original approach to background subtraction is presented for 99mTc-DTPA separate glomerular filtration rate (SGFR) estimation in man. The method is based on the properties of the peripheral organ distribution volume (PODV) in mammillary systems. These PODV properties allow easy separation of the components of the renogram, i.e., interstitial fluid, plasma and renal activities. The proposed algorithm takes advantage of the linear time dependence of the kidney distribution volume, during the renal uptake phase, to correct for the plasma residual activity, which always remains after classical background correction. Theoretically, the ratio between kidney uptake and SGFR should be identical for both left and right kidneys, even for very asymmetrical kidney functions. This is best verified when the proposed plasma residual activity correction is applied. PMID- 2213198 TI - The count rate performance of a multiwire gamma camera measured by a decaying source method with 9.3-minute tantalum-178. AB - The multiwire gamma camera (MWGC) operates at high count rates with radionuclides of low energy and short half-life. We evaluate the count rate performance of the MWGC with tantalum-178 (178Ta) by a decaying source method. Data acquired dynamically by the camera from a 178Ta source in the NEMA Standards scatter phantom were corrected for deadtime loss by a trial paralyzing deadtime and converted to their natural logarithms. The trial deadtime, tau, was adjusted iteratively after curve fittings until a straight line was achieved. The paralyzing deadtime determined by this method was 0.41 microsecond. Therefore, the camera can be operated up to 850,000 cps with 178Ta without exceeding 50% data loss. This rate is 10 times greater than the performance of the typical scintillation camera. Moreover, high count rates are achieved without significant loss of spatial resolution. PMID- 2213199 TI - A routine, automated synthesis of oxygen-15-labeled butanol for positron tomography. AB - The use of labeled butanol for autoradiographic and positron tomographic measurement of cerebral blood flow has been well established using radiocarbon labels. The advantages of the short half-life of oxygen-15 (15O) in doing sequential flow studies are also recognized. An automated procedure has been developed for the routine rapid and sequential synthesis of 15O-labeled butanol in amounts and with purity suitable for use in positron tomography. Butanol can now replace 15O-labeled water, which is commonly used for routine applications. The 14N(d,n)15O reaction is used, with 8 MeV deuterons on a nitrogen target containing 0.2% oxygen. Labeled oxygen is reacted with tri-n-butyl-borane by passing the gas over an alumina support which holds the reagent. Washing with water through small C18-bonded phase silica cartridges eliminates labeled water and the majority of boron-containing impurities. Injectable labeled butanol is collected at 2.5 min after the end of bombardment. The yield is 6 mCi per microampere of saturated bombardment, measured at the end of synthesis. Injectable product up to 250 mCi can be obtained at 10-min intervals. PMID- 2213200 TI - Design and use of PET tomographs: the effect of slice spacing. AB - With modern positron tomographs producing 14, 21, or more transaxial slices, the effects of slice spacing on quantitative reconstruction and three-dimensional displays must be evaluated. This analysis can be approached in terms of the partial volume effect, quantified by the recovery coefficient, or in terms of sampling theory leading to the concept of aliasing. The axial recovery coefficient varies as a function of the position of an object in relation to the slices, with greater variability for larger slice spacings and finer axial resolutions. The aliased image power varies in the same way. The variability in the recovery coefficient and aliasing increase when smaller objects are imaged. Tomographs should be designed with slice spacing approximately half the full width at half-maximum axial resolution of the tomograph; finer spacing does not appear to confer significant advantages. Thus, quantification and display in positron tomography depend on slice spacing, resolution, and object size. PMID- 2213201 TI - HMPAO-SPECT imaging resembling Alzheimer-type dementia in mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). AB - Single-photon emission computed tomography (SPECT) of the brain using hexamethyl propylene amine oxime (HMPAO) was performed in a 37-year-old patient suffering from mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). Reduced blood flow was observed bilaterally in the parieto occipital regions (resembling Alzheimer type dementia) and in the right parietal lobe. PMID- 2213202 TI - The usefulness of the 1-hour technetium-99m-HMPAO leukocyte scan in the early diagnosis of acute abdominal sepsis. PMID- 2213203 TI - A new radiochemical method to determine the stability constants of metal chelates attached to a protein. PMID- 2213205 TI - NRC's ACMUI (Advisory Committee on the Medical Uses of Isotopes) meets for first time in two years. PMID- 2213204 TI - Thymic uptake of gallium-67 citrate: adult versus pediatric patients. PMID- 2213206 TI - Maximizing nursing staff development. The learning laboratory. AB - To survive in today's cost-conscious medical-center environment, nursing education must show how it contributes effectively to promoting and maintaining the currency and competency of nursing staff practice, the quality of patient care, and the overall functioning of the medical center. In the face of limited resources, nursing education increasingly must promote staff's self-assessment of their own knowledge and skill deficiencies and use of self-study mechanisms to meet established performance standards. This survey explored the current use of learning laboratory centers used by nursing education for maximizing staff access to and use of needed remedial and practice update learning opportunities. PMID- 2213208 TI - Successful implementation of an automated nurse-information system. Staff development's role. AB - Staff development's role in the selection and implementation of a computer system based on nursing standards of practice is described. The department's instructors successfully helped staff adapt to the change and understand the integrated, automated nurse-information system. The importance of having a teaching plan to provide consistency in training sessions is discussed. PMID- 2213207 TI - An orientation model for correctional-health nursing. AB - A model to assist staff development educators with the orientation of nurses entering correctional health practice is introduced. The model incorporates the nursing process in screening activities, providing direct care, examining health behavior, teaching, and counseling incarcerated persons. The use of an education plan and contract for the adult learner, teaching strategies, method of evaluation and terminal behavioral objectives are discussed. PMID- 2213209 TI - Training health care professionals to enhance their patient teaching skills. AB - Lack of training interferes with health-care professionals' ability to teach effectively. Nursing staff development educators are seeking strategies to overcome teaching-skill deficits. A 30-hour program was designed to improve teaching skills. Evaluation was based on operationally defined teaching skills. Sixty-six course participants' teaching skills improved from the beginning to the end of the course. Further research is needed to determine whether effects persist in practice, whether patients benefit, and whether "training of trainers" is feasible. PMID- 2213210 TI - A supportive, successful refresher program. AB - A community hospital developed a nursing refresher program that offered emotional support to the participants. The support was evident preenrollment, during the refresher course, and in the orientation to employment. Twenty of 27 participants accepted positions at the hospital. A questionnaire sent after graduation indicated that more acceptance from staff nurses was needed in the early months of employment. PMID- 2213211 TI - Enhancing staff's business sense. An economics of health-care module. AB - An in-depth education module on economics was offered for staff nurses that provided the "tools" needed for application in the clinical setting. Module development, the content of each session, examples of maximizing resources, and economic outcomes that contain costs and promote appropriate reimbursement are included. PMID- 2213212 TI - Developing an educational needs assessment. AB - Nurse educators routinely are asked to assess learning needs. Step-by-step guidelines for formulating and implementing an educational needs assessment are provided. The nurse educator who is familiar with conducting a needs assessment can obtain required baseline information to make decisions in various situations. PMID- 2213213 TI - Using a preceptor program to develop nurse managers. PMID- 2213215 TI - Administrator's forum. Performance appraisal systems for nursing staff development specialists. PMID- 2213214 TI - All-day inservice education concept. AB - The All-Day Inservice Program is an ambitious concept with ever-changing variables. Adjustments to ongoing needs are made with the help of a database system to validate decisions. This centralized, time-blocked, mass inservice plan for nursing and ancillary staff still can meet individual needs. PMID- 2213216 TI - Common sense quality management. AB - How would you like to be responsible for an organization that achieved positive patient results, satisfied high-performing nurses, and had a healthy bottom line? Here's a common sense quality management model sophisticated enough to meet your needs and simple enough to implement at all levels of your organization. PMID- 2213217 TI - Shaping the future through a philosophy of nursing. AB - Commitment to a philosophy of nursing requires input by all individual members of a division of nursing. The author describes the process of developing and introducing a new philosophy of nursing, including task force selection and preparation, review of potential strategies to develop a philosophy, details of the process used, and an introduction of the new philosophy to staff members. PMID- 2213218 TI - Understanding the tools for managing cash. AB - An institution's survival in the 1990s depends on its ability to generate enough cash to meet its needs. The author discusses two accounting tools, the cash budget and the statement of cash flows, that help monitor and control cash flows. By understanding the nature and impact of each report, nurse administrators can help safeguard one of their institution's scarcest resources: cash. PMID- 2213219 TI - Public relations. Part I, A skill for nurses. AB - Public relations is a part of marketing. It is concerned with the promotion of a positive image of organizations and individuals. In this two-part series, the authors discuss how nurse administrators, managers, intrapreneurs, and entrepreneurs can use public relations strategies and techniques to advance their careers, organizations, and the profession. Although JONA readers may be familiar with many of these strategies, nurse administrators may wish to use the series to make their entire professional nurse staff aware of the value of the public relations process when it is operationalized throughout the nursing division. Part I describes the development of public relations, its role in marketing, nursing's publics, and the steps of the public relations process. It ends with the application of this process to career development. PMID- 2213220 TI - The full-service hospital: an employer's dream. PMID- 2213221 TI - Adjunct executive appointment for faculty. An innovation in nursing collaboration. AB - The need for collaboration has never been greater. The healthcare delivery system faces unprecedented challenges arising from prospective payment, competition in the marketplace, higher patient acuity levels, and a shortage of professional nursing staff. The authors discuss a service-education collaboration model based on adjunct executive appointments of faculty members to healthcare organizations. The authors describe the model, a conceptual framework to guide its development, case studies of its implementation, and a summary of the benefits and risks associated with the initial implementation of the model. PMID- 2213222 TI - The nursing research model at St. Elizabeth's Hospital, Boston. PMID- 2213223 TI - Nursing care delivery systems. A nursing administrative practice perspective. AB - The Nursing Administrative Practice Perspective (NAPP) is a macro, ecologic, open systems, conceptual model. This model guides the discovery, understanding, prediction, and use of key resources, structures, goals, and processes in the delivery of nursing care. NAPP encompasses and expands upon established domains of nursing, person, health, and environment as they influence nursing administration practice. A heuristic device, NAPP advances the understanding of relationships between nursing administrative practice, nursing care delivery systems, and organizations. PMID- 2213224 TI - Professional standards and ethical dilemmas in nursing information systems. AB - A significant challenge for the next decade is the design and implementation of nursing information systems that enhance patient outcomes and professional standards in nursing. Computer vendors have the potential to drive nursing practice by dictating what gets documented as nursing care. Ethical dilemmas related to appropriate roles for nurses in designing, developing, using, and validating computer systems need careful consideration. The author suggests ways nurse administrators can get involved in this important process. PMID- 2213225 TI - Leadership in transition. PMID- 2213227 TI - Ultrastructure of the digestive tract, Part I. PMID- 2213226 TI - Legal implications of restraints. PMID- 2213228 TI - Extrusion of colonic epithelial cells in vitro. AB - Rat colonic mucosae fixed in situ in Ussing chambers provided a model of the extrusion of absorptive enterocytes and less commonly of goblet and enteroendocrine cells. The cells were lost at extrusion zones midway between crypt mouths. Even in mucosae in which the number of extruding cells was large, epithelial continuity was maintained as evaluated morphologically and electrophysiologically. Beneath points of remaining contact between desquamating cells and the epithelial sheet, microfilaments of the terminal web formed band like structures linking adjacent junctional complexes. Freeze-fracture replicas disclosed extensive macular regions of tight junction strands in the plasma membranes of desquamating cells. Tight junctions between newly neighboring cells were often irregular and often occurred beneath the terminal web region. Dithiothreitol enhanced cell loss and increased basal epithelial conductance, but histological continuity was maintained and the mucosae continued to respond typically to bradykinin. These observations suggest that during the loss of senescent enterocytes, tight junctions are maintained; old junctional elements are lost, and tight junctions are formed between remaining adjacent cells. This model offers a means to study the synthesis and turnover of tight junctions and the maintenance of the colonic epithelial barrier. PMID- 2213230 TI - Lowicryl embedding of gastrointestinal tissues. AB - In the present study, we modified the technique described by Altman et al. (J. Histochem. Cytochem., 32:1217-1223, 1984) for rapid embedding of tissues in Lowicryl K4M. To attain good sections of the small intestine that contained villi, crypts, submucosa, and external muscle layers, we cut 100 micron slices of the full thickness of the wall with a vibratome before embedment and then deoxygenated the resin and tissue before polymerization. The sections we obtained compared favorably with the quality of sections from conventional resins. PMID- 2213229 TI - Lectin binding patterns to plasmalemmal glycoconjugates of goblet cells undergoing differentiation in vitro. AB - The plasmalemmal glycoconjugates of the HT29-18N2 (N2) cell line were characterized on cells grown as 1) undifferentiated multilayers in glucose containing culture media and 2) monolayers of columnar cells acquiring the goblet cell phenotype in glucose-free media. Lectins were unable to bind sheets of detached N2 cells in the absence of fixation. Following fixation with aldehydes, a dramatic unmasking of lectin binding sites was seen. When fixed monolayers were stained prior to embedding, biotinylated lectins, visualized by the avidin-biotin complexed peroxidase technique, were more efficient than collodial gold-coupled lectins. Lectin binding sites could also be detected by using collodial gold coupled lectins to stain monolayers embedded in LR White, Lowicryl K4M, and Lowicryl HM20. The binding of 5 lectins (wheat germ, Dolichos bifluros, peanut, soybean, and Ulex europeus) was found to be independent of the stage of differentiation; "pre-differentiated" columnar cells which had prominent microvilli and no or few mucous secretory granules had identical staining patterns as well-differentiated goblet cells with large numbers of secretory granules. Ricinus communis I was the only lectin whose binding was influenced by the stage of differentiation; it intensely labeled undifferentiated multilayers of N2 cells but only weakly labeled basolateral membranes of differentiated monolayers. Canavalia ensiformas (ConA) caused a moderate and even labeling of both apical and basolateral membranes of fixed monolayers stained prior to embedding, but post-embedding labeling revealed heavy labeling along the lateral margins of all columnar cells and weak to moderate binding along the apical and basal cell surface. PMID- 2213231 TI - Striated brush border of intestinal absorptive epithelial cells: stereological studies on microvillous morphology in different adaptive states. AB - Different regions of small bowel were examined in five groups of rats in three separate experiments. The effects on mucosal morphology of position along the bowel, induced hypoproliferation (due to fasting), and induced hyperproliferation (due to streptozotocin diabetes) were investigated. Intestines fixed by in situ perfusion with buffered glutaraldehyde were sampled by strictly randomised procedures. Pieces of tissue from segments of roughly equal length were processed for electron microscopy and embedded in resin. Complete transverse sections were cut for light microscopy and estimates of villous surface areas were obtained by stereological methods devised for the purpose. Ultrathin sections from random sectors of the same tissue blocks were sampled systematically to obtain micrographs of the villous surface. These were analysed for quantitative information about microvilli (length, diameter, surface area, and number). Structural quantities from individual segments were pooled to provide values for the entire small bowel. Significant regional differences in villous and microvillous dimensions were found in all groups. The numbers of microvilli per bowel were remarkably constant in all control groups. Other variables were estimated reproducibly in rats of the same sex, strain, and average body weight. Effective absorptive surfaces did not show a linear gradient but tended to peak in middle segments. Neither fasting nor induced diabetes altered the mean length, diameter, or packing density of microvilli. However, surfaces due to villi and microvilli altered commensurately during fasting and induced diabetes. Therefore cell number seems to be the key quantity for determining villous and microvillous surface areas. The findings are discussed in the context of kinetic, biochemical, and physiological changes found in different adaptive states. PMID- 2213232 TI - Fasting induces modifications of the endoplasmic reticulum in intestinal cells. AB - The polymorphism of the endoplasmic reticulum (ER) in epithelial cells with different transport functions such as the enterocyte suggests that the ER may be involved in some way in molecular transport. To further access this possibility, we examined the ER from the intestine of winter flounder, Pseudopleuronectes americanus, a species which undergoes an annual fast of approximately 6 months' duration, a time during which previous work indicates nutrient carrier number does not change. Fish from June (feeding) and January (8-10 weeks fasted) were sampled. Tissues from the pyloric caeca, foregut, midgut, and hindgut were prepared for electron microscopy using two techniques of staining. Cell height was unaltered in any section, although microvillar length shortened variably. Cellular organization, including position of nuclei, number and distribution of mitochondria, and presence of basolateral membranes, did not change. The ER appeared equally abundant in June and January. However, use of the osmium impregnation technique, which is specific for ER cisternal contents, revealed a change in the impregnation of ER, from a heavily impregnated network in summer to little or no impregnation in winter. These results suggest that a shift in function of the ER had occurred when nutrient transport ceased, and supports a role of the ER in nutrient transport. PMID- 2213233 TI - Ultrastructure of Paneth cells in the intestine of various mammals. AB - Paneth cells in the following species were observed under an electron microscope: human, rhesus monkey, hare, guinea pig, rat, nude rat, mouse, golden hamster, and insect feeder bat. Secretory granules containing homogeneous electron-dense materials were observed in the Paneth cells of humans, monkeys, hares, guinea pigs, and bats; mouse Paneth-cell granules were bipartite (central core and peripheral halo), and the Paneth cells in rats and golden hamsters had secretory granules showing various electron densities. In humans, monkeys, and bats, immature granules near the Golgi apparatus sometimes showed bipartite substructure. The number and size of secretory granules were also diverse among various animal species. Some lysosome-like bodies were commonly observed in peri- or supranuclear regions, though the size and shape of the bodies differed from cell to cell. In apical cytoplasm, small clear vesicles (100-200 nm diameter) were more-or-less observed in all species examined, and it was especially note that rat Paneth cells contained many clear vesicles. Small dense-cored vesicles (150-200 nm diameter) were rare. It is unlikely that the various ultrastructural features of Paneth cells correlate with the phylogenetical classification. PMID- 2213234 TI - Fast processing of black and white films used in the EM lab. AB - Kodak black and white film emulsions 4489, 4162, 2415, TMAX-100, TMAX-400, MPD-4 and RPC-651 can be developed in less than 10 minutes on a film processor, quickly printed on resin coated paper and dried with auto-processor and dryer. Adjustments to the ASA (ISO) to compensate for increased contrast with auto processing are described. PMID- 2213235 TI - Modification of grid storage boxes for processing in electron microscopy immunocytochemistry. PMID- 2213237 TI - A new method for phase identification for electron diffractionists. AB - An accurate analytical procedure for phase identification for electron diffractionists has been developed. The method opens new frontiers in the identification of solid-state materials, as crystalline samples in the size range 10 microns to 10 A can be accurately characterized. Research with NIST CRYSTAL DATA (a large database with chemical, physical, and crystallographic data on solid-state materials) has proved that a material can be uniquely characterized on the basis of its lattice and chemical composition. To characterize a material, it is sufficient to determine any primitive cell of the lattice and the element types present. Using a modern analytical electron microscope (AEM), the experimentalist can collect the required data on an unknown sample. The lattice information is obtained by rotation of the sample to obtain two or more planes of data. From these planes, a unit cell defining the lattice can be deduced. The chemical data are determined by energy-dispersive spectroscopy (EDS). Once the experimental data are measured, the unknown is identified against the database of knows using lattice/element-type matching techniques. The basic strategy consists of three conceptual steps. First, the unknown lattice is searched against the database to find all lattices that are the same or related; the results are kept in set 1. Second, the unknown is searched against the database to find all materials with the same or similar element types; the results are kept in set 2. Finally, the results in sets 1 and 2 are combined to obtain the answer set. Experience has proved that the procedure is highly selective and reliable. PMID- 2213236 TI - Ultrastructure of sperm, spermiogenesis, and sperm-egg interactions in selected invertebrates and lower vertebrates which use external fertilization. AB - This review discusses the ultrastructure of sperm with reference to their development, the surface morphology of the egg, and the processes of sperm binding and penetration during fertilization. These topics are treated for selected invertebrates and lower vertebrates which live in aquatic environments and fertilize their eggs externally. Specifically, sperm eggs from cnidarians, echinoderms, decapod crustaceans, ascidians, lampreys, bony fishes, and amphibians are discussed. Sperm from the majority of these groups exhibit the classical head-midregion-tail configuration characteristic of primitive sperm. Specific variations within this general morphology have been described. The notable exceptions to the primitive-sperm paradigm are the sperm of decapod crustaceans and amphibians. Eggs from all of the animals considered are covered by complex vitelline envelopes except those of cnidarians. In general, the ultrastructural analysis of these egg envelopes shows that they are composed of fibrous subunits. Sperm bind to the vitelline envelope and then penetrate through it to fertilize the egg in all groups reviewed except fishes. In sperm ultrastructure which occur during penetration of the egg envelopes in both flagellated and non-flagellated sperm. These changes, which involve membrane fusion and reorganization as well as movement of membranous organelles, aid the sperm in reaching the actual site of gamete fusion. PMID- 2213238 TI - A stopped-flow/rapid-freezing machine with millisecond time resolution to prepare intermediates in biochemical reactions for electron microscopy. AB - We have developed an instrument capable of freezing transient intermediates in rapid biochemical reactions for subsequent freeze-fracturing, replication, and viewing by transmission electron microscopy. The machine combines a rapid mixing unit similar to one widely used in chemical kinetics (Johnson, 1986) with a propane jet freezing unit previously used to prepare static samples for freeze fracturing (Gilkey and Staehelin, 1986). The key element in the system is a unique thin-walled flow cell of copper that allows for injection and aging of the sample, followed by rapid freezing. During freeze-fracturing, a tangential cut is made along the wall of the flow cell to expose the sample for etching and replication. The dead time required for mixing and injection of the reactants into the flow cell is less than 5 ms. Electronic controls allow one to specify, on a millisecond time scale, any time above 5 ms between initiation of the reaction and quenching by rapid freezing. PMID- 2213240 TI - A review of echinoderm oogenesis. AB - This review of the anatomical, histological, biochemical, and molecular biological literature on echinoderm oogenesis includes the entire developmental history of oocytes; from their inception to the time they become ova. This is done from a comparative perspective, with reference to members of the five extant echinoderm classes; crinoids, holothurians, asteroids, ophiuroids, and echinoids. I describe the anatomy and fine structure of the echinoderm ovary, with emphasis on both the cellular relationships of the germ line cells to the somatic cells of the inner epithelium, and on the neuromuscular systems. I review the literature on the growth of oogonia into fully formed oocytes, including the process of vitellogenesis, presenting an ultrastructural analysis of the organelles and extracellular structures found in fully formed echinoderm oocytes. Echinoderm oocyte maturation is reviewed and a description of the ultrastructural, biochemical and molecular biological changes thought to occur during this process is presented. Finally, I discuss oocyte ovulation, the severing of cellular connections between the oocyte and its surrounding somatic epithelial cells. PMID- 2213239 TI - A simple pneumatic device for plunge-freezing cells grown on electron microscopy grids. AB - A detailed design for a simple and inexpensive variable-speed (1.0-5.8 m s-1) pneumatic plunge-freezing device is presented. Cultured cells, grown on Formvar coated 75-mesh gold finder grids, are pneumatically driven into a stirring mixture of propane/isopentane (3:1) cooled by liquid nitrogen (LN2). Premature freezing of the sample in the cryogenic vapors above the cryogen is prevented by plunging through an entry tube into an insulating box, to which a partial vacuum is applied. The cryogenic vapors are drafted into the box at the level of the liquid cryogen by the vacuum, thereby preventing a layer of cold gas from collecting above the cryogen. To prevent the sample from thawing during transfer from the cryogen to the substitution medium, the box top is removed and compressed air is forced through a corrugated tube running the length of the box. The resulting boiling LN2 creates an atmosphere below -120 degrees C in which the transfer can be accomplished. PMID- 2213241 TI - Herbert R. Bird (1912-1989). PMID- 2213242 TI - Effect of dietary fat source on lipoprotein composition and plasma lipid concentrations in pigs. AB - Most studies of the effects of dietary fat sources on plasma lipid components have used diets with extreme fat compositions; the current study was designed to more nearly mimic human dietary fat intake. Young growing pigs were fed diets containing either 20 or 40% of energy as soy oil, beef tallow or a 50/50 blend of soy oil and tallow. Different dietary fats did not affect concentrations of cholesterol, triacylglycerol or protein in plasma or major lipoprotein fractions. The concentration of phospholipid was less in plasma and in very low density lipoproteins with soy oil feeding than with tallow feeding. The weight percentage of cholesteryl ester in the low density lipoprotein fraction tended to be greater with 40% than with 20% tallow and tended to be less with 40% than with 20% soy oil. Phospholipid as a weight percentage of low density lipoprotein was least in pigs fed soy oil. Tallow feeding increased the percentage of myristic, palmitic, palmitoleic and oleic acids in plasma, relative to both other groups. Soy oil feeding increased the percentage of linoleic and linolenic acids. These moderate diets were not hypercholesterolemic, but they did alter plasma fatty acid composition and phospholipid concentrations in plasma and very low density lipoprotein. PMID- 2213243 TI - Effects of excess dietary tyrosine on cholesterol, bile acid metabolism and mixed function oxidase system in rats. AB - Excess dietary tyrosine (12%) caused hypercholesterolemia in male Wistar rats and significantly increased cytochrome P-450 and b5 contents. Bile flow and biliary output of total bile acids were significantly increased in rats fed this diet. Biliary output of cholesterol was not significantly altered, whereas that of taurocholic acid was significantly increased. Excess dietary tyrosine significantly decreased the fecal excretion of neutral steroids, whereas total steroid excretion was not significantly changed. The present results indicate that excess dietary tyrosine causes hypercholesterolemia without modifying the fecal total steroid excretion, thus supporting our previous hypothesis that stimulated synthesis of cholesterol is a main reason why excess dietary tyrosine leads to hypercholesterolemia. PMID- 2213244 TI - Effect of vitamin C depletion on serum cholesterol and lipoprotein levels in ODS (od/od) rats unable to synthesize ascorbic acid. AB - The effect of ascorbic acid deficiency on serum and liver cholesterol, phospholipid and triglyceride levels, serum lipoprotein levels and serum lipoprotein cholesterol levels were examined in male rats with a hereditary defect in ascorbic acid synthesis (ODS rats). Male homozygotes (od/od) and male rats of their parent strain (+/+) were each divided into four treatment groups and were fed vitamin C-deficient or vitamin C-replete diets containing either 0 or 0.5% cholesterol. During the 3-wk feeding-period the ODS (od/od) rats fed the vitamin C-deficient diet gradually decreased food intake, resulting in a lower body weight than that of od/od rats given ascorbic acid. The serum cholesterol level was significantly higher in the vitamin C-deficient od/od rats fed the cholesterol diet, and it tended to be higher in those fed the control (0% cholesterol) diet, whereas the liver lipid levels remained unchanged relative to those in od/od rats fed the vitamin C-replete diet. The serum very low density lipoprotein and high density lipoprotein (HDL) cholesterol levels were lower in od/od rats fed the vitamin C-deficient diet without cholesterol, but intermediate density lipoprotein and low density lipoprotein cholesterol levels were markedly higher in the vitamin C-deficient od/od rats than in od/od rats given ascorbic acid, regardless of dietary cholesterol level. The ratio of HDL2 cholesterol to HDL3 cholesterol was also higher in the vitamin C-deficient od/od rats. The parent strain of the od/od rats (+/+) showed no change due to vitamin C deficiency. These results suggest that vitamin C deficiency delays low density lipoprotein metabolism and produces hypercholesterolemia in male od/od rats. PMID- 2213245 TI - Adaptation of lingual lipase to dietary fat in rats. AB - To study the adaptive response of lingual lipase and pancreatic lipase to dietary fat, three sets of experiments were performed in adult male rats. In the first experiment, rats were fed for 3 wk a low fat diet (4.5% fat) or a 10, 20 or 30% fat diet. In the second, rats were fed a 4.5% fat diet for 4 wk or a 20% fat diet for 1, 2 or 4 wk. In the third, rats were fed for 3 wk a 10% fat diet with various sources of fat (lard, sunflower oil, olive oil, peanut oil, butter, soybean oil, corn oil or salmon oil). The results demonstrated that 10% dietary fat was sufficient to promote a maximum significant increase in lingual lipase activity (expressed in units/g tissue and in units/mg protein), whereas pancreatic lipase responded steadily to 20 and 30% fat diets. After 1 wk of feeding 20% dietary fat, both enzyme specific activities had reached their maximum values. The fatty acid composition of dietary triglyceride molecules (chain length, number and location of double bonds) had no specific effect on the adaptation of lingual lipase. The physiological implications of these findings are discussed in regard to the role of intragastric lipolysis in fat digestion. PMID- 2213246 TI - Elevation of retinol levels and suppression of alanine aminotransferase activity in the liver of taurine-deficient kittens. AB - In taurine-deficient cats, the secretion of bile acids is impaired, and this impairment may reduce intestinal uptake of lipophilic vitamins. It was therefore hypothesized that retinol deficiency is involved in the generation of retinal lesions in taurine-deficient kittens. To this end, the concentration of retinol in plasma and liver was determined in taurine-deficient kittens. Further, the effects of taurine deficiency on amino acid concentrations of heart, liver and kidney were investigated. To see whether taurine deficiency adversely affects the liver, hepatic enzymes were measured in plasma and liver of kittens suffering from taurine deficiency. In addition, liver morphology, growth and food intake were studied. Taurine was the only amino acid whose concentration was consistently decreased in plasma of the experimental group. Unexpectedly, retinol level was increased in plasma and liver from taurine-depleted kittens. Several alterations were noted in amino acid concentrations in liver and kidney, but not in heart. Plasma alanine aminotransferase activity was diminished, probably reflecting decreased activity in the liver. Perivenular steatosis was found in both groups. Controls grew linearly, in contrast to deficient animals, which nevertheless consumed more food. The results demonstrate that retinol deficiency is not involved in taurine-deficiency retinopathy. Moreover, taurine is required for linear growth of juvenile cats and for the maintenance of hepatic and renal pools of certain amino acids. PMID- 2213247 TI - Oxidation of the supplemental methionine source L-2-hydroxy-4-methylthiobutanoic acid by pure L-2-hydroxy acid oxidase from chicken liver. AB - The peroxisomal enzyme L-2-hydroxy acid oxidase A (EC 1.1.3.1) was isolated from chicken liver to better evaluate its part in the utilization of the L isomer of supplemental DL-hydroxy-4-methylthiobutanoic acid by birds fed diets containing the methionine hydroxy analogue. The 650-fold purified enzyme, a 169 kDa protein composed of four apparently identical subunits, exhibited a specific activity of 1.3 mumol glycolate oxidized.min-1.mg protein-1. Glycolate (Km = 0.10 mmol/L) was actually a better substrate than L-2-hydroxyisocaproate (Km = 0.63 mmol/L), L-2 hydroxy-4-methylthiobutanoate (Km = 1.73 mmol/L) and L-lactate (Km = 10.13 mmol/L). Under all substrate concentrations tested, the enzyme activity toward L 2-hydroxyisocaproate and L-2-hydroxy-4-methylthiobutanoate was 55 and 17%, respectively, of that toward glycolate. Although the highly purified enzyme was unable to oxidize D-lactate, D-methionine, L-methionine, L-mandelate and beta phenyl-L-lactate, the latter two aromatic substrates were significantly oxidized by the first ammonium sulfate precipitate obtained during the isolation procedure, supposedly because of the presence of L-2-hydroxy acid oxidase isozyme B. Because the hepatic tissue concentration of glycolate, the physiological substrate for the enzyme, was rather low (10 mumol/L) as compared to the concentration of the methionine hydroxy analogue, one can expect that the conversion of L-2-hydroxy-4-methylthiobutanoate to 2-keto-4-methylthiobutanoate prior to L-methionine formation might proceed at a substantial rate in chickens fed the supplemental methionine source. PMID- 2213248 TI - Enhancement of sulfhydryl group availability in the intestinal brush border membrane by deficiencies of dietary calcium and phosphorus in chicks. AB - The reactivity and availability of sulfhydryl (-SH) groups in brush border membranes (BBM) from chicks adapted to a calcium-deficient (low Ca) or a phosphorus-deficient (low P) diet were determined. The calbindin-D28K concentrations of the intestinal mucosa of the low Ca and low P groups were both increased approximately 2.5-fold, demonstrating that adaptation to the mineral deficiencies had occurred. By the Ellman reaction, a threefold increment in -SH groups in BBM from both mineral-deficient groups was noted. By using DACM (N-7 dimethylamino-4-methylcoumarin-3-yl maleimide), a fluorescent probe for -SH groups, it was observed that fluorescence development was considerably greater with BBM from the low Ca and low P groups than with BBM from the controls, whether measured in the absence or presence of sodium dodecyl sulfate (SDS). In the absence of SDS, the pseudo-first-order reaction rate constants, k', calculated from the fluorescence data, were greater than the control group values, but in the presence of SDS, the k' values for all groups were about the same. Similar changes in BBM-SH groups were previously observed when 1,25 dihydroxycholecalciferol was given to vitamin D-deficient chicks. The redox state of the sulfhydryl groups in enzymes and transport proteins is known to affect the level of their activity. The functional significance of the present observations concerning the -SH groups of chick intestinal BBM, particularly in relation to vitamin D-dependent calcium and phosphorus absorption, is not known but is under investigation. PMID- 2213249 TI - Iron-induced metallothionein in chick liver: a rapid, route-dependent effect independent of zinc status. AB - The induction of hepatic metallothionein (MT) by the parenteral administration of iron was studied. Iron administered to chicks by intravenous or subcutaneous injection caused a 1.9-fold increase in hepatic MT. In marked contrast, intraperitoneal (ip) Fe resulted in a 10-fold increase, thus demonstrating the importance of the route of metal administration. This route-dependent effect was found to be dose-dependent, with ip injections between 1 and 10 mg Fe/kg resulting in a linear increase in MT and a concomitant reduction in serum zinc concentration and feed intake. High ip doses of Fe resulted in a persistent depression in serum Zn and elevated MT and MTmRNA. Equimolar ip injections of either Zn or Fe showed similar patterns of MTmRNA accumulation. In both cases MTmRNA levels were elevated by 3 h, with a peak at 6 h postinjection (Fe 8-fold, Zn 12-fold above 0 h). Plasma Zn was maximally reduced by Fe at 9 h (60%). The MT induction by Fe, as well as related depression in plasma Zn, was completely inhibited by actinomycin D. Zn depletion eliminated the accumulation of hepatic Zn and MT protein following ip injection of Fe or endotoxin, but not of cadmium, despite marked elevation of hepatic MTmRNA. Our results demonstrate Fe injected into the body cavity of chicks results in a rapid induction of hepatic MT that, like endotoxin induction, is independent of dietary Zn status. PMID- 2213250 TI - Effects of inflammation and copper intake on rat liver and erythrocyte Cu-Zn superoxide dismutase activity levels. AB - Stress such as inflammation produces an acute phase response that includes elevated levels of ceruloplasmin, the main copper component of plasma. Inflammatory effects on cellular copper enzyme activity levels are largely unknown. Cu-Zn superoxide dismutase (SOD) activities in liver, the main site of ceruloplasmin secretion, decreased with turpentine-induced inflammation (0.1 mL, intramuscular, leg) in rats fed any of three copper levels (adequate = 6 mg/kg, marginal = 2.5 mg/kg and deficient less than 0.5 mg/kg). Ceruloplasmin activities rose significantly with inflammation in the adequate and marginal groups but not in the deficient animals. Hepatic Cu-Zn SOD immunoreactive protein levels were unaffected by copper status or inflammatory state. Erythrocyte Cu-Zn SOD activities were influenced by dietary copper but not inflammation. An additional group of rats fed 15 mg copper/kg did not show a turpentine-induced decrease in liver Cu-Zn activity levels. Inflammatory effects on other copper enzyme activities did occur as evidenced by increases in ceruloplasmin and decreases in serum extracellular SOD. In conclusion, an acute phase response in rats increased the amount of dietary copper required to maintain hepatic Cu-Zn SOD activity at levels equal to those of nonstressed, copper-adequate rats. Rat erythrocyte Cu-Zn SOD activities provided a blood measurement reflective of copper intake with or without stress, but these values did not reflect decreases in liver Cu-Zn SOD activities after 3 d of inflammation. PMID- 2213251 TI - Effects of graded dietary levels of Spirulina maxima on vitamins A and E in male rats. AB - The effects of ingesting the alga Spirulina maxima on the storage and utilization of vitamins A and E were investigated by feeding diets containing 0, 2.7, 10.7, 18.7 and 26.7% S. maxima to male rats for 6 wk. All diets contained 18% protein, which was contributed by S. maxima or by casein or by a mixture of them. Growth results indicated that rats did not utilize the diets containing S. maxima as well as the casein control diet (0% S. maxima) when levels were 10.7% or more of the diet. The ingestion of S. maxima caused a significant increase in dry matter and chloroform-extractable crude fat in the feces. A low level of 2.7% S. maxima caused a significant reduction in plasma, liver and heart alpha-tocopherol levels. The concentrations of alpha-tocopherol in these tissues showed a marked decline with 10.7% S. maxima in the diet, followed by a lesser decline at higher levels. Liver retinoid levels of rats increased when S. maxima was added to the diet, suggesting conversion of the naturally occurring carotenoids in S. maxima to vitamin A. However, the plasma levels of retinol decreased when S. maxima was fed at 10.7% or more. These data demonstrate that S. maxima can significantly alter the storage and utilization of vitamins A and E. PMID- 2213252 TI - Comparison of the effects of dietary glucose versus galactose on porcine feto placental glucose metabolism. AB - The present study was conducted to determine whether dietary galactose can be used to improve glycogen and lipid accretion in fetal pigs. Pregnant gilts were fed diets containing either 24% glucose (control) or 24% galactose from d 98 to 110 of gestation. Gilts underwent abdominohysterotomy on d 110 of gestation. Slices of fetal subcutaneous adipose tissue and placenta were examined for metabolic capacity for glucose and for galactose utilization. No effects of maternal diet were evident upon glycogen content or enzyme activity of fetal semitendinosus muscle and liver. Maternal dietary galactose had no direct effects upon placental glucose oxidation or use for lipid synthesis. However, galactose supplementation of the incubation medium caused reductions in glucose oxidation (15%) and total lipid synthesis (24%) by the maternal placenta. Maternal dietary galactose caused an increase in total lipid (50%) and fatty acid synthesis (200%) from glucose in fetal subcutaneous adipose tissue; direct supplementation of galactose to the incubation medium had no effect on these parameters. The results of the present study suggest that feeding galactose to the pregnant gilt does not have direct effects upon placental metabolism or fetal glycogen storage. However, these data indicate that use of galactose in the maternal diet can result in an increase in the utilization of glucose for lipogenesis by fetal adipose tissue in swine. This effect is not a direct effect of galactose because transport across the placenta was not apparent. PMID- 2213253 TI - Organ hypertrophy and responses of colon microbial populations of growing swine to high dietary protein. AB - Thirty-two castrated male crossbred growing pigs (average initial wt 26.9 kg) were used to determine the effect of a high level of dietary protein (37%) compared with a normal level of protein (15%) on enterobacteria and Campylobacter sp. inhabitation in the large intestine and on visceral organ hypertrophy and the interrelationships between these two factors. Pigs were kept in pairs (eight pens of two pigs/diet) and fed their respective diets and libitum. Eight pigs (two pens of two pigs fed each diet) were killed at wk 4, 8, 12 and 16 without fasting. Fecal samples were obtained every 2 wk from animals scheduled for necropsy at 16 wk, and colon contents were obtained from all pigs at necropsy; samples were enumerated individually for enterobacteria and Campylobacter sp. Weights of heart, lungs, liver, kidneys, perirenal fat and empty stomach, small intestine and large intestine were recorded at necropsy. Stomach, cecum and proximal colon were sectioned for histopathologic examination. Daily body weight gain was depressed by high dietary protein, but liver and kidneys were heavier in the high protein group than in controls at each time interval. Mild lymphoid hyperplasia of Peyer's patches in the small intestine in some pigs in both groups was indicative of antigenic stimulation but not of pathologic significance. There was no effect of diet on counts of enterobacteria or Campylobacter sp. in feces or colon contents during the 16-wk experiment. We conclude that the hypertrophic response of the tissues of growing pigs to high dietary protein is not the result of the presence of Campylobacter sp. or enterobacteria in the colon contents. PMID- 2213255 TI - IVACG statement on vitamin A depletion and deficiency in childhood. PMID- 2213256 TI - What is evaluation: nurse decision-makers' perceptions of program evaluation. AB - This study investigates alternate reasons for conducting program evaluation in community health care settings and their relationship with information needs. One hundred and thirty-six community health nurses representing New York state associations were the decision makers used in the survey. Results indicated that the most frequent reasons cited for conducting program evaluation were accreditation and standard control. These were followed by need for information for formative program changes and aiding decision makers. Participatory and scientific evaluation purposes were rated last. When examining information sources, respondents were unable to differentiate needs on an independent item-by item basis; all items were considered important. When asked, however, to select the most critical items of these sources, a pattern of needs was established. Decision makers felt that program goals, identification of staff concerns, and presentations of client opinions were the most crucial types of information. PMID- 2213254 TI - Effect of dose of bovine somatotropin on nutrient utilization in growing dairy heifers. AB - Growing Holstein heifers [n = 6; 104 kg initial body weight (BW)] were used to investigate the effects of a daily dose (0, 6.7, 33, 67, 100 and 200 micrograms/kg BW) of bovine somatotropin (bST) on nutrient utilization. A Latin square design was used, and treatments (daily doses of bST) were administered by intramuscular injection for 14-d periods. Intakes of a total mixed ration were adjusted according to BW at the start of each period. Energy was supplied to allow an estimated daily gain of 0.75 kg, and crude protein intake was increased 15% above recommendations to allow for anticipated increases in protein deposition with bST treatment. Nitrogen balance and nutrient digestibilities were determined on d 7 to 13, and blood samples were obtained on d 14 of treatment. Digestibilities of dry matter, organic matter and N were similar (70 +/- 1%) and not affected by treatments (p greater than 0.1). Nitrogen retention increased, and plasma urea N and urinary N excretion decreased in a dose-dependent manner. Retention of N in heifers receiving the highest bST dose was 23% greater (p less than 0.001) than the zero dose treatment. Serum concentration of insulin-like growth factor I (IGF-I) was also increased with bST treatment in a curvilinear dose-dependent manner. Plasma glucose increased (5 to 8%, p less than 0.001) with the three highest doses of bST, but serum concentration of insulin was not altered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213257 TI - Forging a nursing research agenda for New York State. AB - The Foundation of the New York State Nurses Association Inc., (hereafter Foundation), the Council on Nursing Research of the New York State Nurses Association (hereafter Council on Nursing Research), and the Delta Pi Chapter of the Sigma Theta Tau International (hereafter Delta Pi), sharing the same beliefs about nursing research and the need to take action, have worked cooperatively during the past three years to develop a nursing research agenda for New York state. Activities undertaken by these three groups to achieve this goal include co-sponsored conferences, a delphi survey to establish nursing research priorities for New York state, a research program offered at the 1989 Convention of the New York State Nurses Association, and establishment of the Foundation's Center for Nursing Research. A Planning Committee, with representatives from the three co-sponsoring organizations, has been appointed to assist the Center to further specify the action strategies for the research agenda and to oversee implementation of the agenda. PMID- 2213258 TI - Methodological pluralism in clinical nursing research. AB - Clinical nursing research can benefit from an approach that blends discovery oriented qualitative methods with the objective, numerically based quantitative methods. This paper describes current approaches to clinical research in either the quantitative or qualitative paradigm. The strengths and weaknesses of each of these approaches are discussed. A rationale for methodological pluralism--the blending of the two methods--to understand clinical phenomena is presented. PMID- 2213259 TI - Survey response rates to a professional association mail questionnaire. AB - The purpose of this research was to study the effect of various direct mail techniques on professional nurses' response rates to questionnaires. A random sample of 700 registered professional nurses consisting of five groups who were members of New York State Nurses Association (NYSNA) were mailed a questionnaire with 22 items. The study demonstrated that the response rates were directly attributable to techniques used. Providing information about the association was related to significantly decreased response rates and monetary incentives with significantly increased response rates. A combined direct mailing for questionnaire completion and membership solicitation was not effective for either purpose. PMID- 2213260 TI - On friendship, infant formulas, and business: a minority opinion. PMID- 2213261 TI - A randomized, controlled application of the Wallaby phototherapy system compared with standard phototherapy. AB - The feasibility and efficacy of a fiberoptic blanket (Wallaby Phototherapy System) for the treatment of physiologic jaundice was compared with conventional phototherapy. Forty-two full-term infants with nonhemolytic jaundice were included in the study. Infants in the study group were treated with the fiberoptic blanket and the infants in the control group were placed under a standard phototherapy unit. Both the fiberoptic blanket and the standard phototherapy unit delivered an average irradiance of 7.0 +/- 0.5 muw/cm2/nm. Incremental changes in serial plasma bilirubin levels compared with the initial bilirubin concentration did not differ between the study and control groups. For infants whose initial plasma bilirubin concentration exceeded 200 mumol/L, a statistically significant difference was found in both study and control groups between the average bilirubin level at initiation of phototherapy and the average bilirubin level at termination of treatment. We conclude that phototherapy delivered by the fiberoptic blanket is safe and has efficacy comparable to that of conventional phototherapy, providing a convenient alternative phototherapy application strategy that obviates the need for eye patches and facilitates maternal handling of the infant during therapy. PMID- 2213262 TI - A new device for phototherapy treatment of jaundiced infants. AB - A new device for phototherapy consisting of a fiberoptic panel attached to an illuminator was compared with traditional phototherapy (4 special blue and 4 daylight bulbs). The panel surrounds the trunk eliminating eye patching and allowing more time for maternal-infant interaction. Forty-six jaundiced term neonates were studied. Two groups, nonhemolytic (n = 26) and hemolytic (ABO) (n = 20) jaundice, received fiberoptic or traditional phototherapy. In both groups, fiberoptic and control patients had similar weights, gestational ages, bilirubin levels and ages at entry. Post-therapy weights and duration of therapy were also similar. In the nonhemolytic fiberoptic group, there was a trend toward greater decreases in mean bilirubin levels at 12, 24, 36, and 60 hours with significant reduction at 48 hours of therapy (-2.8 vs -.5 mg/dL; P = .04). In the hemolytic group, bilirubin fell continuously in the fiberoptic group and after 36 hours in the traditional group. At 36 hours there was a trend toward a greater decrease in mean bilirubin for the fiberoptic group (-1.8 vs + 1.9 mg/dL; P = .08). There were no complications of therapy. The fiberoptic panel proved effective and safe; eliminated the need for eye patches; and permitted greater time for maternal infant bonding. PMID- 2213263 TI - A new method of phototherapy: nursing perspectives. AB - Phototherapy is commonly used to treat infants with hyperbilirubinemia. Conventional phototherapy consists of a light source situated approximately 20 inches from an infant who is in an isolette and who is equipped with eye patches. A new method of phototherapy, a fiberoptic blanket, wraps light around the infant's torso delivering continuous phototherapy. The infant can remain in the mother's room in an open crib during treatment without the need for eye patches. We have found this system to have many advantages over conventional phototherapy for hospitalized infants with hyperbilirubinemia. PMID- 2213264 TI - Prolongation of the latency period in preterm premature rupture of the membranes using prophylactic antibiotics and tocolysis. AB - Mixed results have been obtained in several studies using tocolysis or antibiotics individually in the treatment of premature rupture of membranes (PROM). We compared the outcomes of a management protocol consisting of tocolysis, prophylactic antibiotic administration, and documentation of pulmonary maturity with a control group treated with passive expectant management for premature rupture of membranes. There were 55 women in the treatment group and 57 women in the control group. The mean latent phase (+/- SEM) in the treatment group was 7.34 (+/- 1.25) days compared with 1.86 (+/- .431) days in the control group (P less than .001). Eighteen of 55 patients (33%) in the treatment group were electively delivered after documentation of lung maturity, contributing to a falsely lowered mean latent phase in the treatment group. Twenty-four patients in the treatment group and 6 in the control group had a latent phase of 5 days or greater (P = .00018). There were 9 postpartum infections in the control group and 10 infections in the treatment group (P = NS). There was no difference in the length of latent phase of patients treated with ceftizoxime compared with the other antibiotics used (cefoxitin, cefazolin, ampicillin), although postpartum ceftizoxime was more effective in preventing postpartum infections (1 of 28 vs 9 of 27) (P = .005). There were fewer infected neonates in the study group, but this was not significant. It appears that treatment with this protocol significantly prolongs the latent phase in patients with preterm PROM without increasing infectious morbidity. PMID- 2213265 TI - Twenty-four hour in-house coverage for neonatal intensive care units in academic centers: who, how, and why? AB - Twenty-four-hour in-house coverage by attending physicians is becoming more common in academic centers in certain subspecialties in pediatrics. The actual percentage of programs providing this coverage in most subspecialties is not documented. We report the results of a survey of in-house coverage by attending physicians in neonatal intensive care units at academic centers in the United States. Of the 238 surveys distributed, 204 (86%) were returned and completed. At the time of the survey, 47 of 204 programs (23%) provided 24-hour in-house coverage for their neonatal intensive care units. These programs had more manpower than those programs not providing this coverage. If this trend continues, it will significantly alter projections for neonatal manpower needs in the United States. PMID- 2213266 TI - Perinatal outcome of singleton pregnancies conceived by in vitro fertilization: a controlled study. AB - To determine whether conception by in vitro fertilization and embryo transfer (IVF) predisposes to perinatal complications, the obstetric records of 54 women delivered of singleton pregnancies after conception by IVF were examined. Control women were matched for age, parity, race, year of delivery, diethylstilbestrol exposure and medical problems; another group of women who conceived after infertility treatment was matched in similar fashion. IVF patients showed a longer first stage of labor than previously infertile women, experienced a greater intrapartum blood loss than control or previously infertile women, and showed a trend toward a higher cesarean delivery rate than control women. The differences noted probably do not arise from the physiology of IVF, and although some differences are statistically significant, they are of minimal clinical significance. Singleton pregnancies arising after IVF should not be considered as high risk in the absence of other predisposing factors. PMID- 2213267 TI - Fluctuations of arterial blood pressure decrease with mechanical ventilation in premature infants with respiratory distress syndrome. AB - Marked fluctuations of arterial blood pressure (ABP) are associated with an increased risk of intraventricular hemorrhage. The pathophysiology is linked to spontaneous breathing. We hypothesized that these fluctuations would decrease after initiation of effective mechanical ventilation. We studied 20 infants treated with nasal continuous positive airway pressure (CPAP) and oxygen for early respiratory distress. Eleven required intubation for clinical indications. Simultaneous ABP and respiratory tracing obtained before and following intubation were analyzed for average peak systolic blood pressure (SBP) and the percentage of spontaneous respirations (SResp). Fluctuations of SBP were quantitated using the coefficient of variation (CV). The remaining 9 infants with minimal lung disease served as a control group. There was a small increase in SBP, and a marked decrease in both CV and SResp following intubation. A significant correlation was found between the percent decreases in CV and SResp. We conclude that beat-to-beat fluctuations of ABP decrease after the initiation of effective mechanical ventilation. This effect is primarily due to a decrease in spontaneous breathing. PMID- 2213268 TI - Fatal Streptococcus viridans septicemia and meningitis: relationship to fetal scalp electrode monitoring. AB - Viridans streptococci have been reported as an increasingly frequent pathogen in neonatal sepsis. These infections have appeared to be less virulent than those associated with other bacteria. The case of an infant is reported who developed a scalp abscess secondary to an internal fetal monitoring electrode caused by viridans streptococci. This infection evolved into a rapidly fatal septicemia and meningitis. Viridans streptococci may be responsible for virulent fatal infections in neonates. PMID- 2213269 TI - Mothers' behavior with home infant apnea monitors. AB - This study presents findings from 35 interviews with mothers of infants who were monitored for apnea following discharge from the same neonatal intensive care unit. The interviews took place at a mean of 28 weeks following discontinuation of the infant home apnea monitor and focused upon the mothers' behavior with the monitor. One family had independently ceased to use the monitor within 1 week of their infant's hospital discharge. All other mothers reported always having used the monitor at night, and 92% always used it during their infants' daytime naps. Approximately one half of the mothers would not have been able to consistently hear an alarm, however, when their infant was asleep. Consistency of availability to a monitored infant was not related to the mothers' background, attitudes, or experiences with their infant. These data indicate the need to emphasize for all caregivers the importance of being available to their monitored infant at all times. PMID- 2213270 TI - Obstetric care of a Southeast Asian refugee population in a midwestern community. AB - The obstetric records of 430 Hmong and other Southeast Asian refugee women were retrospectively reviewed from January 1, 1977 to July 1, 1988. All patients gave birth in two hospitals in a midwestern community, La Crosse, Wisconsin. Lack of medical care for early pregnancy complications, late onset of obstetric care, anemia, and high rates of parasites and hepatitis occurred frequently in pregnancy. Admission in advanced labor, a low operative delivery rate (6%), and a higher prematurity rate characterized intrapartum care. Birthweight data revealed statistically significantly smaller infants after 38 weeks' gestation. Postpartum febrile morbidity and neonatal complications were rare. Cultural differences and their effects on obstetric care are discussed. PMID- 2213271 TI - Diabetes mellitus in pregnancy: clinical review. PMID- 2213272 TI - Establishing a neonatal resuscitation team in community hospitals. AB - Recent national guidelines for neonatal resuscitation state that personnel trained in resuscitation skills should be immediately available for every delivery. Meeting this standard is a challenge for small community hospitals with limited staff and few 24-hour in-house physicians. We have developed a strategy for organizing neonatal resuscitation teams in community hospitals and describe our experience with establishing such teams in our region. Suggestions for implementation include: identifying a project organizer, involving all relevant staff in the decision making, writing a formal protocol, and planning a schedule for implementation. Often team members will be nurses or other professionals in expanded roles, the only stipulation being that they be immediately available and well trained. Recommendations are made for training and scheduling of neonatal resuscitation team members and for the contents of the resuscitation protocol. Barriers to successful implementation are discussed, including liability concerns or lack of confidence among team members, nonacceptance of expanded roles by other professionals, and difficulties with scheduling, equipment maintenance, and risk assignment. Nevertheless, successful establishment of a neonatal resuscitation team can effectively reduce the risk of neonatal asphyxia in small community hospitals. PMID- 2213273 TI - Imaging procedures and developmental outcomes in the neonatal intensive care unit. AB - Behavioural and environmental modification techniques in the neonatal intensive care unit for oxygen-dependent premature infants with chronic lung disease have been shown to result in a decrease in the number of days of respirator support and number of days of supplemental oxygen therapy. Long-term neurodevelopment outcome was significantly better for infants in the experimental therapy group who received specialized environmental modification to decrease stressful stimuli. We present results of cranial ultrasound and chest radiograph studies in this very high-risk population and suggest that such studies represent additional stressful stimuli that should be scheduled with consideration of an overall behavioral infant care plan. PMID- 2213274 TI - Polemics in perinatology: in praise of activism. PMID- 2213275 TI - Neonatal ultrasound casebook. Bladder fungus ball in disseminated candidiasis. PMID- 2213276 TI - Ventilatory management casebook. Direct extubation from low intermittent mandatory ventilator rate. PMID- 2213277 TI - Neonatal surgery casebook. Congenital aplasia of iliac veins. PMID- 2213278 TI - Neonatal radiology casebook. Pulmonary venous gas embolism. PMID- 2213279 TI - Intact survival and 20-month follow-up of a 380-gram infant. AB - Intact survival of infants delivered before completion of the 26th week of gestation or weighing less than 500 g is a well-known phenomenon. We recently cared for an infant whose birthweight was 380 g, making her the second smallest survivor in the United States. Her hospitalization (including expenses) and 20 month (corrected) follow-up are presented along with a discussion of the implications involved in the care of such an infant. PMID- 2213281 TI - ABO incompatibility. PMID- 2213280 TI - The effectiveness of a cardiopulmonary resuscitation program for mothers of newborn infants. PMID- 2213282 TI - The future role of diuretics in the treatment of hypertension. PMID- 2213283 TI - Long-term clinical trials in hypertension. AB - Long-term clinical trials of antihypertensive therapy have demonstrated that diuretic-based therapy consistently reduced fatal and non-fatal cerebrovascular events regardless of age, race or gender; the frequency of ECG left ventricular hypertrophy, retinopathy and progression of hypertension were also reduced, and cardiomegaly and ECG left ventricular hypertrophy were reversed. A case can be made for initiating antihypertensive therapy whenever diastolic blood pressure remains greater than or equal to 90 mmHg despite a fair trial of non pharmacologic treatment. Elderly patients with diastolic hypertension benefit from diuretic-based therapy at least until the age of 80 years. Whether ACE inhibitors or calcium channel blockers are more effective than diuretics in preventing cardiovascular complications remains to be seen. So far, there have been no long-term trials using these agents as initial therapy. PMID- 2213284 TI - The cardiotoxicity of thiazide diuretics: review of the evidence. AB - Careful consideration of all relevant scientific evidence and a critical assessment of data quality show that thiazide diuretics are not cardiotoxic. Of 12 reported trials only two recorded more coronary heart disease events in thiazide-treated patients than in controls. One of these two was a subgroup of a larger study (Heart Attack Prevention in Primary Hypertension, HAPPHY) which found no difference between thiazide-treated and beta-blocker-treated patients. The other, the Oslo study, was too small to allow valid conclusions. Results from a subgroup in the Multiple Risk Factor Intervention Trial (MRFIT) that appeared to supply evidence for thiazide-related cardiotoxicity are suspect when examined critically. Further evidence from 24- to 28-h ECG monitoring does not support the hypothesis that thiazide diuretics, either in the presence or absence of hypokalemia, increase the frequency or severity of ventricular arrhythmias. Reports of a thiazide-induced intracellular magnesium deficiency as a cause of ventricular arrhythmias have also not been confirmed; the development of arrhythmias in acute myocardial infarction appears to be due to an increase in catecholamine levels rather than hypokalemia. There appears to be little evidence to support the assumption that long-term use of thiazide diuretics aggravates or accelerates atherosclerosis of the coronary arteries; any fall in serum cholesterol appears to be transient. For the great majority of patients with uncomplicated hypertension, without a previous myocardial infarction, congestive heart failure, diabetes mellitus or gout, thiazide diuretics appear to be both safe and effective antihypertensive agents. PMID- 2213285 TI - Diuretics and blood pressure reduction: physiologic aspects. AB - Among the many classes of diuretics available, thiazides have emerged as the most appropriate category for the treatment of uncomplicated hypertension. Potassium sparing agents may be added according to need or in fixed-combination therapy. Thiazides act on the cortical diluting segment of the renal tubule. The potassium sparing agents interfere with the Na(+)-K+ exchange process in the terminal part of the distal tubule. Thiazides have been the cornerstone of therapy in nearly all prospective therapeutic, mild and moderate hypertension trials conducted to date. They have, therefore, proved their value in the prevention of hypertensive cardiovascular complications such as stroke and congestive heart failure. The physiologic changes occurring during antihypertensive treatment with thiazides have been extensively studied. The initial response to a thiazide is characterized by a mildly negative change in sodium and fluid balance. The resulting slight contraction in plasma volume is followed by reductions in cardiac output and blood pressure. Because these reductions are disproportionate, vascular resistance rises initially. In the longer term, plasma volume is partly restored, and cardiac output re-attains the baseline level. Thus, the reduction in blood pressure ultimately appears to be based on vasodilation. The mechanisms of this biphasic vascular response are not completely understood. This lack of insight, however, does not detract from the proven value of thiazides in treating hypertensive subjects. PMID- 2213286 TI - Diuretics for elderly patients. AB - Diuretics compare well with the large number of other classes of antihypertensive agents now available as first-line treatment in the elderly. Other drugs might be considered for first-line treatment in elderly patients with diabetes, untreated gout, or renal failure, a previous myocardial infarction or multiple ventricular ectopics and for men concerned about potency. A thiazide with a potassium-sparing agent may be preferred in the elderly population. The most telling feature in favor of diuretics is that they comprise the only group of drugs for which a beneficial effect in reducing cardiovascular disease in the elderly has been demonstrated in clinical trials. Although compliance may decline somewhat with age, compliance rates of 80% or more can be expected, even among very elderly patients. PMID- 2213287 TI - Spatial variability as a limiting factor in texture-discrimination tasks: implications for performance asymmetries. AB - Texture-discrimination tasks reveal a pronounced performance asymmetry depending on which texture represents the foreground region (small area) and which represents the ground (large area). This asymmetry implies that some global processes are involved in the segmentation process. We examined this problem within the context of the texture-segmentation algorithm, assuming two filtering stages. The first stage uses spatial frequency and orientation-selective (Gabor) filters, whereas the second stage is formed by low-resolution edge-detection filters. The presence and location of texture borders are indicated by significant responses in the second stage. Spurious texture borders may occur owing to textural local variabilities (such as orientation randomization), which are enhanced by the first stage. We suggest that these spurious borders act as background noise and thus limit performance in texture-discrimination tasks. The noise level depends on which texture occupies the ground in the display. We tested this model on numerous pairs of textures and found remarkably good correlation with human performance. A prediction of the model, namely, that discrimination asymmetry will be reduced when textural elements have identical orientation, was tested psychophysically and confirmed. PMID- 2213288 TI - Chromatic induction and brightness contrast: a relativistic color model. AB - It has been suggested that object colors in a colored environment are the result of combining in perception the (relative) brightness of each spectral component rather than of just mixing the spectral luminances. We tested this hypothesis with the following experiment: A pair of center-surround targets made of colored papers was illuminated with trichromatic white light. Two identical central color plates (test and match field, respectively) were surrounded by frames of different colors and thus looked different because of simultaneous color contrast. Observers were asked to match the colors by changing the illumination of the match field by means of a color-mixture projector (color match, CM). This color-matched reflectance was measured with a photometer, and its CIE coordinates were determined. We then illuminated the display with one of the three primaries that made up our trichromatic white light. The different reflectances of the different surrounds at each primary induced simultaneous brightness contrast. The brightnesses of the two central plates were therefore different. Observers were asked to change the intensity of the illumination of the match field at the respective primary so that it looked equally bright as the test field. This procedure was repeated for each primary (primary brightness match, PBM). Then the whole display except for the match field was illuminated with the trichromatic white as before, while the latter was illuminated with a trichromatic mixture consisting of the primaries at the intensities as set in the PBM experiment, and the CIE values were determined with the photometer. The CIE values of the match field after the CM and PBM procedures were nearly identical. This indicates that composite colors are composed in perception by combining the scaled (or relative) brightness of each spectral component and that this brightness scaling is largely restricted to interactions in the same spectral region. The results are compared with those of other models concerned with contrast colors as well as with neurophysiological data. Some limitations are mentioned. PMID- 2213289 TI - Adaptive and remodeling changes in the fractured mandibular condyle after open reduction using the Kirschner pin. AB - Six cases of fracture of the mandibular condyloid process in which there was osteosynthesis using the Kirschner pin were followed radiographically for more than 1 year. Tracings were made to analyze the remodeling process. The clinical course of all patients was satisfactory, without functional disturbance or asymmetries of the mandible. PMID- 2213290 TI - A prospective evaluation of the effectiveness of temporomandibular joint arthroscopy. AB - This is a prospective study to evaluate therapeutic arthroscopy for internal derangement of the temporomandibular joint (TMJ). Fifty-nine patients with 76 abnormal joints were evaluated preoperatively for pain, noise, maximal incisal opening (MIO), and deviation on opening. Preoperative and postoperative magnetic resonance imaging (MRI) scans were obtained for 29 joints. Patients were treated by superior joint arthroscopy, lysis of adhesions, lavage, and steroid injection, along with preoperative and postoperative splint and physiotherapy. Pain, noise, and motion were evaluated at three time periods: 1) early (10 to 30 days); 2) intermediate (1 to 6 months); and 3) late (greater than 6 months). At early, intermediate, and late follow-up, increase in MIO was statistically significant (P less than .05). Noise did not return in the majority of patients. Disc position, evaluated by MRI, did not appear to change in 25 of 29 joints and did not correlate with clinical outcome. The results of this study indicate that TMJ arthroscopy is effective in reducing pain and increasing motion in patients with TMJ internal derangement. PMID- 2213291 TI - Treatment of the retained permanent molar. AB - The effect of five different treatments for retained permanent molars was evaluated in 59 patients to develop a rational guideline for adequate therapy. The results showed that a prosthetic buildup is the proper treatment if retention develops after the growth spurt, because in these cases the extent of infraocclusion is slight and relatively stable. If retention develops before the growth spurt, immediate removal of the retained molar followed by orthodontic treatment is the way to maximal success. When retention develops during the growth spurt, the tooth affected has to be observed at 6-month intervals. In such a case, no active treatment is indicated if the neighboring teeth show no tilting and the extent of infraocclusion is minor and stable. In all other cases, the teeth affected have to be removed, followed by orthodontic closure of the edentulous space. Finally, all patients must be screened regularly, because in this investigation, new cases of retention were observed relatively frequently. PMID- 2213292 TI - Management of delayed union and nonunion of maxillary osteotomies. AB - Delayed union and nonunion of maxillary osteotomies are unusual, but have been seen with a variety of surgical moves. Management of these problems can be divided into early and late therapy. Four cases are presented illustrating some of these methods of treatment. PMID- 2213293 TI - Morbidity associated with incompletely erupted third molars in the line of mandibular fractures. AB - A retrospective analysis of 105 mandibular fractures associated with incompletely erupted third molars was undertaken. It was found that there was no difference in the rates of complication if the teeth were retained or extracted, or if an open or closed reduction was performed. The combination of tooth retention with open reduction, however, shows a trend toward being the treatment most prone to postoperative complications. PMID- 2213294 TI - Composite temporalis pedicle flap as an interpositional graft in temporomandibular joint arthroplasty: a preliminary report. AB - Fifteen temporomandibular joint patients were evaluated preoperatively and postoperatively to evaluate the effectiveness of a composite (fascia, muscle and periosteum) temporalis pedicle flap as an interpositional disc replacement. A modified Craniomandibular Index (CMI) and Symptom Severity Index (SSI) were used to assess clinical and subjective symptoms. Eighteen months postoperatively there was a significant reduction in the CM and SS indices (P less than .001), with significant clinical improvement of the mandibular range of motion (P less than .05). However, a significant reduction of translation (P less than .01) was evident indicating that the increased mandibular opening was owing to a compensatory rotational movement. This study indicates that the composite temporalis pedicle flap is a good autogenous tissue for the reconstruction of the temporomandibular joint. PMID- 2213295 TI - An evaluation of sensory changes and pain relief in trigeminal neuralgia following intracranial microvascular decompression and/or trigeminal glycerol rhizotomy. AB - Nineteen patients with trigeminal neuralgia were treated with either trigeminal ganglion glycerolysis or glycerolysis and intracranial microvascular decompression. All had a good degree of pain relief. Of those receiving glycerol alone (group A), 50% subjectively reported a mild reduction of fine tactile sensation. A similar response was reported by those treated with both glycerol and decompression (group B). The degree of sensory loss was so mild that thermal testing was useless as a discriminatory tool. The degree of sensory loss was not greater when both surgical procedures were performed than when the less-invasive trigeminal ganglion glycerolysis alone was used. PMID- 2213296 TI - Persistent facial swelling in a 62-year-old woman. PMID- 2213297 TI - The string and the doorknob: profile of a popular approach to dental extraction. AB - Dental technology and delivery of care constantly improve. At the same time, certain folk traditions and attitudes towards dentistry remain curiously constant. Dental extraction using string is an enduring amateur technique, images of which are still widely perpetuated among the laity, in western society. The historical development of extraction as a treatment modality and the rise of dentistry are discussed in relation to the patient's view of dental therapy. Various examples from art and literature are introduced to give depth and perspective to current popular perceptions. Extraction with string is presented as a metaphor for all extractions and as reflective of the public's continuing psychological sensitivity to surgical intervention in the oral cavity. PMID- 2213298 TI - Angioleiomyoma of the nasal cavity. PMID- 2213299 TI - Unilateral pharyngeal plexus injury following use of an oropharyngeal pack during third-molar surgery. PMID- 2213300 TI - Necrotizing soft-tissue infections of dental origin. PMID- 2213301 TI - Vascular leiomyoma of the nasal cavity: report of a case and review of literature. PMID- 2213302 TI - Invasive squamous cell carcinoma of the mandible presenting as a chronic osteomyelitis: report of a case. AB - A case of invasive squamous cell carcinoma of the mandible initially thought to be chronic osteomyelitis is reviewed. Discussion of the origin of the tumor and several imaging techniques used for differentiating maxillofacial infection from neoplasm are discussed. The difficulty of diagnosis of chronic painful maxillofacial lesions illustrates the need for a high degree of suspicion concerning any inflammatory lesion not responding to appropriate therapy. Accurate diagnosis and treatment of such lesions most often necessitates microscopic examination. PMID- 2213303 TI - Symmetrical placement of implants in the edentulous mandible: a new technique. PMID- 2213304 TI - Split-thickness skin grafts from surgically removed autogenous skin. PMID- 2213305 TI - Protection of the lingual nerve during placement of rigid fixation after sagittal ramus osteotomy. PMID- 2213306 TI - Teaching specialists to practice as well as treat. PMID- 2213307 TI - What it takes to make a pretty face. PMID- 2213308 TI - Assessment of Proplast-Teflon disc replacements. AB - This retrospective study reports the findings in the follow-up of 31 temporomandibular joints in which Proplast-Teflon (Vitek Inc, Houston, TX) replacements were used. Among the problems noted were pain, malocclusion, restricted opening, and degenerative changes in the condyle and fossa. PMID- 2213309 TI - A protocol for management of temporomandibular joint ankylosis. AB - A management protocol for temporomandibular joint (TMJ) ankylosis consisting of 1) aggressive resection, 2) ipsilateral coronoidectomy, 3) contralateral coronoidectomy when necessary, 4) lining of the TMJ with temporalis fascia or cartilage, 5) reconstruction of the ramus with a costochondral graft, 6) rigid fixation, and 7) early mobilization and aggressive physiotherapy is presented. The protocol was retrospectively evaluated in the first 14 patients (18 involved TMJs) treated and followed postoperatively for at least 1 year. The facial asymmetries present in all unilateral cases remained corrected. The mean maximum postoperative interincisal opening at 1 year was 37.5 mm (292.36% mean increase), lateral excursions were present in 16 of 18 joints (vs 0 of 18 joints preoperatively), and pain was present in 2 of 18 joints (vs 13 of 18 preoperatively). The results of this study indicate that this protocol is effective for treatment of TMJ ankylosis. PMID- 2213310 TI - Factors associated with soft- and hard-tissue compromise of endosseous implants. AB - This prospective analysis identifies factors associated with endosseous implant removal as well as factors associated with implant morbidity resulting in nonscheduled patient visits. Treatment of the latter conditions is discussed. The most important factors identified for implant success were surgery without compromise in technique, placing implants into sound bone, avoiding thin bone or implant dehiscence at the time of implant placement, avoiding premature implant exposure during the healing period, establishing a balanced restoration, and insuring appropriate follow-up hygiene care. In the posterior mandible, the presence of keratinized gingiva was strongly correlated with optimal soft- and hard-tissue health. PMID- 2213311 TI - An improved technique for development of the pectoralis major myocutaneous flap. AB - The pectoralis major myocutaneous flap is the most commonly employed muscle skin transfer used in soft-tissue reconstruction of defects of the upper neck and jaw region. This article presents conceptual and technical changes in the development of the pectoralis major myocutaneous flap that preserve a greater vascular pedicle and enhance the flap's arc of rotation. Data from 54 consecutive cases using this modified approach show a reduction in complications, a greater range of use, and consistent healing in radiated and nonradiated tissues without requiring sectioning or removing the clavicle or causing significant chest deformities. These modifications have produced a more predictable transfer compared with other reported techniques. PMID- 2213312 TI - Perioral somesthetic sensibility: do the skin of the lower face and the midface exhibit comparable sensitivity? AB - Studies of the perioral somatosensory capacities of neurologically normal adults were reviewed to determine whether sensitivities within the mental and infraorbital nerve distributions are comparable. It was found that tactile detection sensitivity, spatial acuity, and sensitivity to warmth are greater on skin sites located on the midface than on the lower face. In contrast, sensitivity to direction of motion and to differences in surface texture may be greater on skin sites located on the lower face. The literature further suggests that sensitivity within the distribution of each nerve varies appreciably. For example, the vermilion of the lips exhibits considerably greater vibrotactile detection sensitivity, spatial acuity, and sensitivity to direction of motion than does the perioral hairy skin. In addition, spatial acuity is notably greater on midline structures. These findings suggest that knowledge of the patterns of spatial variations in perioral tactile sensibilities can be effectively used during neurosensory examination to select control skin sites for comparison with areas of suspected neurosensory impairment and to distinguish apparent pathological alterations in tactile sensitivity from normal regional differences that characterize the perioral complex. PMID- 2213313 TI - Comparison of functional recovery after nonsurgical and surgical treatment of condylar fractures. AB - This article evaluates 16 cases of condylar fracture treated surgically, comparing them with the 20 cases treated nonsurgically, with a 2-year follow-up. Although severely displaced and luxated fractures were involved in the surgical group with rigid internal fixation, satisfactory postoperative function and occlusion were achieved at the same level as in the nonsurgical group, without severe complications. PMID- 2213314 TI - Firm mass of the tongue. PMID- 2213315 TI - Integration of the medical degree in oral and maxillofacial surgery training: a survey of the American Association of Oral and Maxillofacial Surgeons membership. AB - Fifty percent of the American Association of Oral and Maxillofacial Surgeons membership in the United States was polled in an effort to evaluate the influence a medical degree might have on privileges and referral patterns, and its role in the office, hospital, and academic settings. Biographical data were collected and responses evaluated for the following groups: 1) the nation as a whole, 2) geographic regions of practice, 3) population, 4) number of years in practice, and 5) involvement in academic programs. Questions concerning the spectrum of privileges as well as referrals and desire to possess a medical degree were asked. Substantially different responses were seen between the MD/non-MD oral and maxillofacial (OMF) surgeons as well as differences between geographic locations, years in practice, and academic involvement. In general, MD and academic OMF surgeons possessed a broader spectrum of privileges than their colleagues. No consistent patterns were seen between the various geographic regions. No significant differences existed in privileges based on the size of a community in which a surgeon practices. A greater or equal percentage of privileges was possessed by more recently trained OMF surgeons than their more experienced colleagues. The results presented may aid future graduates in making a more informed decision when considering obtaining a medical degree. PMID- 2213316 TI - Osteomyelitis of the hyoid caused by Torulopsis glabrata in a patient with acquired immunodeficiency syndrome. PMID- 2213317 TI - Arteriovenous fistula: an unusual complication associated with arthroscopic temporomandibular joint surgery. PMID- 2213318 TI - Gorham's syndrome (massive osteolysis): a case report. PMID- 2213319 TI - Elongated styloid process as a cause of difficult intubation. PMID- 2213320 TI - Oral infantile fibrosarcoma: report of a case. PMID- 2213321 TI - Desmoplastic variant of ameloblastoma: report of a case and review of the literature. AB - A case of desmoplastic variant of ameloblastoma is reported. The lesion, in a 36 year-old Japanese woman, was successfully treated by partial maxillectomy. Reconstruction was carried out with a block of hydroxyapatite about 7 years and 6 months later. Six cases, including our case, reported up to the present are summarized and reviewed. PMID- 2213322 TI - A technique for rigid fixation of postcondylar implants. PMID- 2213323 TI - Mucosal reactions to amalgam restorations. AB - Amalgam restorations have been implicated both in contact sensitivity reactions and in lichenoid reactions. This appears to be related principally to the mercury content, although other metals cannot be discounted. The cases of two patients are reported who showed features of lichenoid reactions of the oral mucosa, in addition to features of a contact hypersensitivity to mercury. The mucosal lesions resolved following replacement of the amalgams with non-metallic restorations. Consideration is given to the selection of materials and procedures currently available for treatment of these patients. This paper supports the view that sensitivity to heavy metals must be considered as a possible cause of erythematous and lichenoid reactions of the oral mucosa. PMID- 2213324 TI - Accuracy of impression materials measured with a vertical height gauge. AB - The objectives of this study were to introduce a different method for evaluating the accuracy of impression materials using a vertical height gauge, and to determine the vertical (axial) and horizontal (transversal) changes of four impression materials. Comparison of means demonstrated the changes for addition and condensation type silicones, and larger changes for the agar/alginate combination and the visible light cured (polyetherurethanedimethacrylate) impression material. The results were in agreement with an earlier study of the agar/alginate combination, and the values for the condensation and addition silicones were about half those reported in previous studies. These small changes might indicate the use of a mandibular stock tray for the upper jaw when a putty/wash technique is employed. The findings suggest that, when the horizontal changes (delta X) of impressions taken with a mandibular stock tray have a negative sign (contraction), then the vertical changes (delta L) will have a positive value (expansion), and vice versa. Thus the pattern of distortion can be formulated as delta X/delta L less than 0. PMID- 2213325 TI - A preliminary electromyographic study of bite force and jaw-closing muscle fatigue in human subjects with advanced tooth wear. AB - The maximum bite force was recorded in five experimental volunteers with advanced tooth wear and five control volunteers who showed no abnormal wear. All subjects were then asked to maintain a force of 50% of the maximum for as long as possible while surface electromyograms from the masseter and temporalis muscles were recorded. The bite force and endurance time were found to be slightly increased in the experimental group, but no conclusions could be drawn regarding the state of fatigue. Two significant problems with regard to fatigue studies of the jaw closing muscles emerged from the study, namely the use of the canine position for recording of the force, and the thickness of the force meter. PMID- 2213326 TI - Number of remaining teeth and rehabilitation with removable dentures in psoriatics. AB - The aim of this investigation was to study associations between the state of dentition and socio-medical aspects in psoriatics. It was found that the number of remaining teeth in subjects under 65 years of age was higher in psoriatics with skin symptoms (P-group) than in psoriatics with skin and joint symptoms (PA group) (P less than 0.01), this rate being higher than that found among the general population in Finland. In younger subjects, women in the P-group wore removable dentures more frequently than did women in the PA-group (P less than 0.05), whereas among older subjects men in the PA-group wore removable dentures more frequently than did men in the P-group (P less than 0.001). In the log linear model that was applied, more advanced age, lower level of education and infrequent dental visits were associated with a low number of remaining teeth in both the P-group and the PA-group. A poor general state of health in the P-group and a high number of teeth, indicating that there is an association between severity of general disease and dental health status. PMID- 2213327 TI - An investigation into the microhardness of a light cured composite when cured through varying thicknesses of porcelain. AB - An investigation was carried out to measure the completeness of cure of samples of a composite resin, light cured for 40s and 60s through porcelain discs of varying thickness. Once cured, each specimen was subjected to Vickers microhardness testing to assess the completeness of cure. Composite resin specimens cured without an intervening porcelain disc were used to establish a baseline. The results showed that increasing the thickness of the porcelain disc produced a statistically significant decrease in microhardness of the composite resin. Increasing the cure time from 40s to 60s produced a significant increase in microhardness. The increase in microhardness with increased cure time was more pronounced when the discs of thickness 1 mm and 2 mm were used, and when there was no overlying porcelain disc. PMID- 2213328 TI - Occlusal force distribution in lower complete overdentures. AB - A space between the denture base and a root cap can effectively control the distribution ratio of occlusal force to abutment teeth and an alveolar ridge. The purpose of this study on abutments was to analyse the effect of variation in space (0 mm (no space), 0.3 mm and 0.6 mm) on the above ratio. Six subjects, 38 65 years of age, each with an edentulous maxilla and several teeth remaining in the mandible, were selected for this experiment. The lower experimental denture had embedded a transducer which could detect a change in the vertical force applied to the experimental tooth. This transducer was capable of changing the vertical space between a denture base and an experimental tooth. Each subject was asked to increase the occlusal force applied to the denture from zero to the maximum loading rate of 5 kgf s-1. The occlusal force and the force exerted on the experimental tooth were recorded in each space 1 month after insertion of new dentures. The following results were obtained: (i) when the occlusal force was applied to the artificial tooth just above the abutment tooth, the mean ratio in the 0 mm space was 60% of the force applied to the denture, the ratio in the 0.3 mm space was 50%, and the ratio in the 0.6 mm space was 30%; (ii) if the occlusal force was applied to the point 10 mm distant from the point just above the experimental tooth, the magnitude of the ratio was decreased by 60-80%. PMID- 2213329 TI - Custom overdenture retainer. AB - A simple technique for fabricating stud overdenture retainers in the form of custom attachment castings with teflon retention discs has been described. This system allows for selective placement of the retention sphere on the root surface and control of retention through the size of the retention sphere. Using transfer location projections, exact transfer of the castings to the working model is possible. When necessary, the teflon discs may easily be replaced at the chairside. PMID- 2213330 TI - The effectiveness of dentine adhesives as demonstrated by dye penetration and SEM investigations. AB - A previous investigation identified three types of cuspal movement that occur as a result of polymerization shrinkage when extracted molar teeth are filled with a microfine or hybrid composite used in conjunction with a dentine adhesive. That investigation was extended further by dye penetration and SEM studies of the margin, involving assessment of the degree of dye penetration and marginal integrity around the restoration. These studies indicate that there may be a failure of the adhesive bond between tooth and composite/adhesive complex which correlates with little or no cuspal movement. Failure within the tooth structure itself was also observed in a number of cases. PMID- 2213331 TI - Further studies of some masticatory characteristics of bruxism. AB - Quantitative analysis of a time dependent factor of jaw movement has shown there to be a significant difference in the muscle physiology of non-bruxist and bruxist subjects. Because bruxism can be difficult to detect in some patients, these results indicate that further development of the technique of jaw movement analysis might be useful as a diagnostic tool. They also point to the value of further study into the possible detection of 'potential' bruxists, thus allowing the development of a preventive aspect of bruxism. PMID- 2213332 TI - Viscoelastic properties of tissue conditioners--stress relaxation test using Maxwell model analogy. AB - In order to measure the viscoelastic properties of tissue conditioners, a series of stress relaxation tests was carried out using poly ethyl methacrylate polymer powders and liquids composed of butyl phthalyl butyl glycolate/ethyl alcohol mixtures, respectively. The analysis method using the Maxwell model analogy is discussed. The results may be summarized as follows. (i) In this study it was feasible to make the stress relaxation curves for 30 min analogous to the Maxwell model, using a model with a maximum of 5 elements. (ii) The elastic modulus Ei, the coefficient of viscosity eta i, and relaxation time tau i, for each element, and the instantaneous modulus E0, tended to increase with time. These values in the element of the longest relaxation time were most marked in the increase among those in all the elements. Furthermore, in every element the rate of increase of eta i was greater than that of Ei. The method described is considered to be one of the most useful techniques available for the study of the viscoelastic properties of tissue conditioners. PMID- 2213333 TI - The prevalence of sensitivity to constituents of dental alloys. AB - Ninety-five participants were epicutaneous patch tested in order to determine the prevalence of sensitivity to components of dental alloys. Seventeen individuals (17.9%) developed allergic reactions, which were caused by mercury (10.5%), copper (2.1%), nickel, cobalt, tin, gold and zinc (1.1%). Eight of 17 allergic responders had a history of dermatitis from metal contact. The results show that there is a need for careful immunological considerations during the selection of suitable alloys, particularly in the case of patients with lesions suspected of being caused by dental alloys. PMID- 2213335 TI - Attachment of epiphyseal cartilage cells and 17/28 rat osteosarcoma osteoblasts using mussel adhesive protein. AB - These experiments show that mussel adhesive protein (MAP) enhances the attachment of osteoblasts and epiphyseal cartilage cells to plastic culture dishes and Vitallium. When MAP was applied to culture plate surfaces, there were two- to fivefold increases in the numbers of cells attaching compared to control surfaces (no MAP). Results were confirmed using two different cell attachment assay techniques. Osteoblast replication and culture on MAP is possible, suggesting that MAP is not toxic to cells. MAP also holds applied cells to surfaces as initially attached. PMID- 2213334 TI - Cu-Ti, Co-Ti and Ni-Ti systems: corrosion and microhardness. AB - Titanium alloys of 10 wt%-72 wt% Cu, 10 wt%-80 wt% Co and 20 wt%-84 wt% Ni were investigated. Ingots were fabricated in a vacuum/argon tungsten arc furnace. The surfaces of the alloys were examined by optical microscopy and SEM/EDS, and the Knoop hardness values of the alloys were measured. The corrosion resistance of the alloys was determined by a potentiodynamic polarization technique in buffered Ringer's solution. When a threshold composition of 30 wt% alloy was reached, a large decrease in corrosion resistance was found to occur. Knoop hardness measurements showed that similar hardness values of approximately 300 KHN can be obtained in all systems with lower alloy content. These values are similar to those obtained with a commercial dental titanium alloy. PMID- 2213336 TI - The use of two nutritional indicators in identifying long bone fracture patients who do and do not develop infections. AB - One hundred consecutive orthopedic long bone fracture patients requiring surgical fixation were nutritionally assessed using both the nutritional index of Rainey MacDonald et al. and total lymphocyte count. The ability of these two parameters to identify correctly those patients who do and do not develop postoperative complications was assessed using several error rate measures, which included sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. Fourteen of our patients developed postoperative complications. All complications observed were infections. The accuracy of the nutritional index and total lymphocyte count in predicting patient outcome was 78 and 51%, respectively. The positive and negative predictive values calculated for the nutritional index were 36 and 94%, respectively. Total lymphocyte count analysis resulted in positive and negative predictive values of 15 and 87%, respectively. In our sample of patients, the nutritional index was a better predictor of patient outcome than total lymphocyte count, as indicated by the higher accuracy rate calculated for the nutritional index. Based upon positive predictive value results, neither of these indicators was most accurate in identifying patients who did develop infections. Not unexpectedly, both indicators were best in identifying those patients who did not develop postoperative infections. PMID- 2213337 TI - A model of Staphylococcus aureus bacteremia, septic arthritis, and osteomyelitis in chickens. AB - We studied the occurrence, magnitude, and kinetics of bacteremia and the resultant osteomyelitis and septic arthritis in an avian model of Staphylococcus aureus infection. Thirty-day-old male broiler chicks were inoculated i.v. with 10(5), 10(6), or 10(7) cfu of strain Duntravis, a beta-hemolytic, coagulase producing, capsular type 8 isolate from the synovial fluid of a 2-year-old black boy. Bacteremia occurred in 80%, 90%, and 100% of animals inoculated with 10(5), 10(6), or 10(7) cfu, respectively. The magnitude of bacteremia in surviving, bacteremic animals increased for 96 hours after inoculation and then decreased after a plateau phase. Osteomyelitis and septic arthritis occurred only in chicks that were continuously bacteremic. The occurrence of osteomyelitis was uniform among continuously bacteremic animals and developed 1 to 23 hours after inoculation. Chickens are susceptible to systemic infections with S. aureus. Bacteremia, osteomyelitis, and septic arthritis may be induced in healthy chickens without prior manipulations that depress their resistance. PMID- 2213338 TI - The influence of flexibility on the economy of walking and jogging. AB - The relationship of 11 measures of trunk and lower limb flexibility to the economy of treadmill walking and jogging as measured by steady-state oxygen consumption (VO2) was studied. Subjects (38 women, 62 men, aged 20-62 years) were tested at six speeds between 53.6 and 187.7 m/min. By combining scores from all flexibility tests, and beginning at speeds of 107.3 m/min, the "tightest" third used significantly less O2/m/kg (9%, p less than 0.05) than the "loosest" third, with "normals" in between. Two tests, trunk rotation and lower limb turnout, gave the best separation for walking/jogging economy, with the "tightest" third differing significantly from the "loosest" (8-12%) at all speeds tested (ANOVA with Scheffe). We conclude that nonpathological musculoskeletal tightness was associated with a decreased steady-state VO2 for treadmill walking and jogging. PMID- 2213339 TI - Muscle activities during asymmetric trunk angular accelerations. AB - The objective of this study was to characterize trunk muscle and intra-abdominal pressure behavior during extensions of the trunk when angular trunk acceleration levels and trunk twist were varied during lifting exertions. Since force is related to acceleration, it was believed that changes in trunk acceleration would cause activity changes in the muscles and abdominal cavity pressurization mechanics that load the spine during manual materials handling tasks. The electromyographic activity of 10 trunk muscles and intra-abdominal pressure were studied in 39 subjects as they moved their trunks under high, medium, and low constant angular acceleration conditions. The results indicated that almost all the muscles were affected by acceleration and asymmetry. Muscle activities of up to 50% of maximum were observed even though a minimal amount of torque was being produced by the back. Coactivation of muscles was also apparent. Muscles located at the greatest distances from the spine, such as the latissimus dorsi and oblique groups, increased their activities the most as trunk acceleration increased. Muscles located farthest from the spine also played an important role as the trunk became more asymmetric. Intra-abdominal pressure changed minimally over the test conditions. The nature of these responses and their impact on spine loading are discussed. PMID- 2213340 TI - Evaluation of a microcomputed tomography system to study trabecular bone structure. AB - A new microcomputed tomography (micro-CT) system and thresholding procedure was evaluated as a tool for nondestructive analysis of trabecular bone. Images of 6 mm trabecular bone cubes acquired from the micro-CT system were compared with optical images of corresponding histologic sections to determine the accuracy of representation. The stereologic measures of bone volume fraction (PP) and trabecular plate density (PL) were used to quantify the comparisons. The results showed that the micro-CT measures of PP were not significantly different from those measured from histologic sections and therefore were very accurate. Measures of PL were different by approximately 14%, which translated into discrepancies in trabecular plate thicknesses of about 19 microns. This difference was significantly correlated to the microstructural characteristics of the specific specimen scanned. The precision of both measurements was excellent. PMID- 2213341 TI - A study of fracture callus material properties: relationship to the torsional strength of bone. AB - This study was designed to quantitate the local material properties of fracture callus during gap healing and to relate these local properties to the torsional strength of bone in a canine model under external fixation. Bilateral tibial transverse osteotomies were performed in 32 dogs and stabilized using unilateral external skeletal fixators with a 2-mm gap. Dogs were divided into four equal groups and euthanized at either 2, 4, 8, or 12 weeks. The torsional properties of one bone of each pair were determined. In both bones of each pair, the indentation stiffness, calcium content, and histomorphometric properties of six sites of periosteal callus, six sites of endosteal callus, four sites of cortical bone, and two sites of gap tissue were determined. Each of the four types of tissue had a specific structural or material property change during the study period. The indentation stiffness of periosteal callus increased up to 8 weeks and then plateaued. Endosteal callus stiffness peaked at 8 weeks and then decreased by 12 weeks. Gap tissue stiffness increased linearly over time. Cortical bone stiffness decreased over time. Indentation stiffness was significantly associated with the calcium content of periosteal callus (R2 = 0.50, p less than 0.0001) and gap tissue (R2 = 0.66, p less than 0.0001). The local stiffnesses of gap tissue and periosteal callus were significantly associated with the maximum torque (gap, R2 = 0.50, p less than 0.0001; periosteal, R2 = 0.34, p less than 0.05) and the torsional stiffness (gap, R2 = 0.44, p less than 0.0001; periosteal, R2 = 0.65, p less than 0.0001) of the bone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213342 TI - Torsional strength reduction due to cortical defects in bone. AB - This study correlated torsional strength reduction with circular defect size in cortical bone, to define the "stress riser" and "open-section" effect of the defects. The experimental model was developed and verified. Circular defects from 10 to 60% of bone diameter were then created in paired sheep femora and the bones loaded to failure. Contrary to theory, this experimental study suggests that small defects (10%) of bone diameter cause no significant torsional strength reduction. A 20% defect caused a 34% decrease in strength, representing the "stress riser" dimension. Defects between 20 and 60% of bone diameter decreased strength linearly as a function of defect size, and thus no discrete "open section" dimension was identified. For circular defects, we were unable to demonstrate a discrete "open-section" effect at which dramatic strength reduction is observed. These data may prove to be helpful when planning surgery that involves placing defects in bone such as for infection, biopsy, and prosthesis removal. The accepted guideline to avoid defects of greater than 50% of the bone diameter may be too great. Our data reveal this 62% reduction in torque strength and 88% energy to failure exist with a 50% circular defect. PMID- 2213343 TI - Effects of retinacular release and tibial tubercle elevation in patellofemoral degenerative joint disease. AB - Release of the patellar retinaculum and tibial tubercle elevation have both been advocated for the treatment of patellofemoral degeneration. Questions remain, however, regarding the magnitude and predictability of such effects in diseased joints. Using cadaver knee joints exhibiting a range of patellofemoral cartilage degeneration, we investigated the effects on joint contact pressures on release of the patellar retinaculum, followed by tibial tubercle elevations of 1.25 and 2.5 cm. Retinacular release failed to alter the joint-loading parameters significantly. Tibial tubercle elevation reduced the patello-femoral joint contact area and contact force, but failed to cause a consistent change in contact pressure. Tibial tubercle elevation also caused a migration of the joint contact area superolaterally on the retropatellar surface. This migration occurred in conjunction with ventral tilting of the inferior pole of the patella as the tubercle was elevated, suggesting that significant changes in joint kinematics may result from this procedure. PMID- 2213344 TI - The effect of porous coating processing on the corrosion behavior of cast Co-Cr Mo surgical implant alloys. AB - The manufacture of porous coated cobalt-based surgical implant alloys requires sintering--a high temperature process above the incipient melting temperature of this alloy system. The metallurgical changes produced by the high temperature sinter cycle consist of dissolution of interdendritic carbides, massive precipitation of lamellar carbide eutectic phases at grain boundaries, localized porosity from incipient melting that is not completely eliminated by subsequent hot isostatic pressing, and grain growth in fine-grained materials. These microstructural changes, which are known to affect the mechanical properties, do not affect the static in vitro localized and generalized corrosion behavior of the bulk material as determined by anodic polarization measurements in a buffered saline environment and direct examination by scanning electron and optical microscopy. Additionally, cast Co-Cr-Mo surgical implant alloys are found to be immune to crevice corrosion (in the absence of mechanical fretting) in the saline environment studied. The hysteretic component of the anodic polarization curve is not due to crevice corrosion; rather, as suggested by the electrochemical tests and Auger spectroscopy, the hysteresis is due to redox reactions in the chromium rich surface layer. PMID- 2213345 TI - A quantitative assessment of cross-sectional cortical bone remodeling in the femoral diaphysis following hip arthroplasty in elderly females. AB - A quantitative assessment of cross-sectional cortical bone remodeling in the femoral diaphysis following hip arthroplasty was made by direct in vitro measurements of cross-sectional geometric properties. We obtained eight femora from four female cadavers ranging in age from 77 to 96 years. In three cases unilateral uncemented Austin Moore implants were used, and in one case a unilateral cemented Thompson prosthesis had been implanted. The time of implantation in the two specimens where this information could be obtained was greater than 40 months. Sections were made at 12 diaphyseal locations from the superior aspect of the lesser trochanter through the distal diaphysis. Section properties (areas and second moments of area, or area moments of inertia) were determined by tracing photographs of the cross-sections with a digitizer. In this sample of prosthetic femora, we found reductions in both total subperiosteal area (TA) and endosteal area (ENDA) relative to the contralateral unoperated side in most sections distal to the lesser trochanter. The average pairwise reduction in ENDA for this region was 21.1 mm2, reaching statistical significance in one distal diaphyseal section. The average decline in TA in this region was 10.2 mm2. Because the reduction in endosteal dimensions was generally greater than the reduction in subperiosteal dimensions, cortical area (CA) was maintained or increased throughout the distal 80% of this region in prosthetic femora with an average increase in CA of 9.3 mm2, reaching statistical significance in one mid diaphyseal section. A completely different pattern of remodeling occurred in the two most proximal sections through the lesser trochanter and base of the femoral neck.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213346 TI - The influence of fixation peg design on the shear stability of prosthetic implants. AB - The variety of fixation peg designs existing on prosthetic implants indicates uncertainty regarding the optimum design of fixation pegs for the reduction of stress and relative motion at the bone-implant interface. Fixation pegs have a number of important functions on a prosthesis, one of which is to reduce shear stress and shear displacement at the bone-implant interface. This is a parametric study intended to identify trends in the shear stability of prostheses incorporating a range of fixation peg designs. The parameters varied included the number of fixation pegs on a surface, the size of the pegs, and the aspect ratio (length/diameter) of the pegs. Mechanical tests were performed on urethane foam blocks with mechanical properties comparable to trabecular bone. The results indicated the following: (a) Fixation pegs act independently in resisting shearing force if they are spaced sufficiently far apart. (b) For any given shear displacement, smaller pegs generate a greater resistive shear force per unit of peg projected area in the direction of the applied load than larger pegs having the same aspect ratio. (c) Smaller diameter pegs cause the supporting material to yield at lower displacements. (d) Pegs with a high aspect ratio provide high shear stability with a minimum amount of bone removed, but may bend if the aspect ratio becomes excessive. (e) Smaller, slender pegs generate a greater resistive shear force at a given displacement per unit of peg volume than larger, lower aspect ratio pegs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213347 TI - An animal model for the study of neuromuscular injury induced beneath and distal to a pneumatic tourniquet. AB - A well-controlled animal model is presented for the study of neuromuscular injury induced by a pneumatic tourniquet. This model comprises a curved tourniquet surrounded by a stiff exterior shell, both of which were specifically designed to fit the conical and oblong shape of the rabbit hindlimb. Computed tomographic imaging was used to assess transverse tissue displacement induced by tourniquet compression. The curved tourniquet/shell configuration occluded the distal arterial blood flow to the extremity at a significantly lower cuff inflation pressure than a straight tourniquet of equal width. The magnitude and distribution of tissue pressures in the subcutaneous and deep tissues beneath the tourniquet were similar to those recorded in previous human cadaver studies of tourniquet compression. This animal model will facilitate the quantitation and analysis of tissue injury induced beneath and distal to a pneumatic tourniquet. Such data can help define the critical pressure and time limits for the safe use of pneumatic tourniquets in extremity surgery. PMID- 2213349 TI - Building on our strengths. PMID- 2213348 TI - Dose-dependent variations in blood flow evaluation of canine nerve, nerve graft, tendon, and ligament tissue by the radiolabeled-microsphere technique. AB - This study evaluates the dose-dependent accuracy of the radionuclide-labeled microsphere technique for blood flow evaluation in nerve, tendon, and ligament. In eight dogs, blood flows were determined for nerve, nerve graft, tendon, and ligament tissue by simultaneous injection of high- and low-dose microspheres with different radiolabels. The results demonstrated no significant differences in blood flow as measured from the small number of microspheres (less than 400) and the high number (more than 400) for nerve and tendon tissue. For nerve tissue, microsphere counts of 50 to 100, 100 to 200, 200 to 300, and more than 300 produced mean percentage errors of 12.74% (n = 5, SEM = 4.52), 5.45% (n = 13, SEM = 1.22), 10.22% (n = 6, SEM = 4.37), and 17.08% (n = 12, SEM = 3.30), respectively. For tendon tissue, the same microsphere subdivisions had mean percentage errors of 7.47% (n = 4, SEM = 2.66), 3.63% (n = 6, SEM = 1.34), 15.54% (n = 4, SEM = 4.43), and 12.91% (n = 1), respectively. For ligament tissue, percentage errors were consistently higher; microsphere counts of 30 to 100, 100 to 200, and 200 to 300 produced mean errors of 20.14% (n = 4, SEM = 6.38), 18.66% (n = 4, SEM = 6.24), and 25.78% (n = 2, SEM = 1.97), respectively. Although there was no direct relationship between percentage error and number of microspheres retrieved, we suggest that microsphere counts in the range of 100 to 200 should be considered acceptable for nerve and tendon in the canine. Ligament tissue seems to be less well suited to the microsphere technique; however, further study is warranted. PMID- 2213350 TI - [The influence of maxillary sinusitis upon the posterior fatty layer--a CT investigation]. AB - CT values were estimated at the fatty layer in contact with the posterior wall of the maxillary sinus in various condition, i.e., normal, sinusitis, postop. sinus, and mucocele. By the unilateral sinusitis (40 cases), CT values obtained by the affected sides were significantly higher than those of the non-affected normal sides. A single maxillary bone was used for experiments to show that the dense++ materials filing the sinus do not affect the CT values of the fatty layer, thus confirming the above clinical data was real and not artifact. In addition, by the mucocele of the maxillary sinus (9 cases) with negligible inflammatory change in the sinus, the CT values of the fatty layer did not show any remarkable increase such as seen by sinusitis. These data lead us to the impression that the increased density is due to the transmitted effects of maxillary sinusitis through the posterior wall. In postop, sinuses (11 cases) with various postop. periods, CT values were slightly higher than those in normal sinuses, suggesting that the sinus infection was under improvement. The enhancement performed by 14 cases (28 sides) showed increased density of the fatty layer, but the increase was similar in both affected and non-affected sinuses. This suggests that the increased rate of circulation at the fatty layer is not the contributory factor to higher CT values. The results described above, combined with the previous reports concerning the bony changes in sinusitis, will lead to the conclusion that the increased CT values at the fatty layer is caused by the direct engagement of the inflammatory conditions in the sinus cavities. PMID- 2213351 TI - [A case of cervico-mediastinal abscess, secondary to acute tonsillitis: investigation of the treatments]. AB - No other infectious diseases in the field of otolaryngology cause rapid and lethal course than cervical abscess. A case of cervicomediastinal abscess secondary to acute tonsillitis was presented. The patient was a 43-year-old male with liver cirrhosis and primarily had the treatment of tonsillitis. The complication of duodenal perforation caused marked general deteriotation, and cervical abscess occured. Immediately after transfer to our department, he was treated by cervical drainage, laparotomy and chemotherapy. However, hepatic failure occured, and he died of sepsis on the 16th day after the onset of tonsillitis. Cervicomediastinal abscesses were classified according to severity in Stage 1-4. 34 cases of advanced cervical abscess were reported in Japan from 1976 to 1989. These cases were analyzed statistically in terms of primary focus of infection, surgical procedures, clinical isolates and chemotherapy, etc., and following results were obtained. 1) Primary focus; approximately 50% was due to the infection of the tonsills and the pharynx occupied about 50%, and the odontogenic infections, approximately 40%. 2) Surgical procedures; the neck doranaige approaching through the vertical incision resulted more effective. 3) Clinical isolates; aerobes and anaerobes accounted for 50% each of all strains. alpha-Streptococcus was predominant among aerobes, and Peptostreptococcus and Bacteroides were predominant among anaerobes. In order to confirm pathogenic bacteria of cervical abscess, clinical isolates of peritonsiller abscess and mandibular ostesis were compared with those of cervical abscess, because these infections are primary infectious diseases of cervical abscess.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213352 TI - [Bioelectric properties of excised rabbit nasal mucosa]. AB - The water flow across the respiratory epithelia is an important determinant of the efficiency of mucociliary clearance. Bulk water flow has been shown to be coupled to net ion flux. We studied ion transport across rabbit nasal mucosa by measuring bioelectric properties using Ussing chambers. Results were summarized as follows. (1) Compared with tracheal mucosa, nasal mucosa exhibited lower potential difference (p less than 0.01), lower short-circuit current (p less than 0.05), and higher conductance (p less than 0.01). (2) Ouabain 10(-4)M inhibited short-circuit current when added to the submucosal bath of Ussing chambers, and amiloride decreased short-circuit current to about 40% when added to the mucosal bath. (3) When the bubbling of the solution was changed from 95%O2, 5%CO2 to 100%N2, short-circuit current remarkably decreased. (4) A significant positive correlation existed between temperature ranging from 33 degrees C to 41 degrees C and short-circuit current (r = 0.46, p less than 0.02). PMID- 2213353 TI - [Effects of optokinetic stimulation on head movement and body sway of children]. AB - We evaluated the effects of horizontal and vertical optokinetic stimulation on head movement (HM) and body sway (BS) in children and adults, using a Jung type optokinetic stimulator, a strain gauge-platform, and a encephalography. Twenty healthy children aged 7 to 9 years and twenty healthy adults aged 20 to 26 years were instructed to stand with feet close together on the platform with eyes open with and without optokinetic stimulation for 60 seconds. In all subjects, optokinetic stimulation significantly increased the total lengths of HM and BS. In addition, optokinetic stimulation significantly increased the areas of HM and BS in children, but not in adults. Although the ratio of the anteroposterior component to the lateral component in BS was significantly higher in children than in adults, the value of HM was not. Children exhibited a characteristic BS in which the anteroposterior swaying velocity was larger than the lateral swaying velocity. In the anteroposterior component, averaged divisional frequencies of BS were significantly larger in children than in adults. However, averaged divisional frequencies in the lateral component of BS and those in the anteroposterior and lateral components of HM did not differ between the two age groups. The ratio of the total length of HM to that of BS was significantly higher in children than in adults. These results suggest that HM and BS of children are readily affected by optokinetic stimulation, and that in children, the BS velocity in the anteroposterior direction is higher than that in the lateral direction. PMID- 2213354 TI - [Neuro-otological examination in patients with unilateral cerebral lesion- fixation suppression]. AB - Fixation suppression of caloric nystagmus was examined in 33 cases with unilateral cerebral vascular lesion. Only Lesion included the unilateral internal capsule was certified by CT scan in all of the subjects. The rate of fixation suppression (FS%): FS% = (1 - F/D) x 100 was calculated by the mean slow-phase velocity (F) of caloric nystagmus during fixation and the maximum slow-phase velocity (D) during eyes open in darkness. The normal FS% of nystagmus to both sides was observed in 12 cases, the reduction of FS% of nystagmus to the ipsilateral side of the lesion was observed in 11 cases, that of nystagmus to the contralateral side in one, and that of nystagmus to the bilateral side in eight. In 30 out of 32 cases which were able to measure the slow-phase velocity (SPV) of caloric nystagmus, FS% of nystagmus to the ipsilateral side of the lesion was lower than that to the contralateral side, and there was statistically a significant difference between them (p less than 0.05). Furthermore, the difference between the SPV of nystagmus to the ipsilateral side of the lesion and that to contralateral side was examined during fixation and during eyes open in darkness separately. The SPV of nystagmus to the ipsilateral side of the lesion was significantly (p less than 0.01) higher than that to the contralateral side during fixation. There was no significant difference between them during eyes open in darkness. In 15 cases, however, tonic eye deviation over 20 degrees to the slow-phase side was only observed during nystagmus to the ipsilateral side.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213356 TI - [Reflex control on laryngeal functions--vibration effect of the laryngeal mucosa on recurrent laryngeal nerve reflexes]. AB - Electromyographic (EMG) responses of the intrinsic laryngeal muscle have been investigated to clarify reflexogenic laryngeal controls from a viewpoint of its functional significance during phonation. Twenty-five adult cats were anesthetized with intraperitoneal injection of 4ml/kg of a mixture of 10% urethane and 1% alpha-chloralose. Either the internal branch of the superior laryngeal nerve (ISLN) or the recurrent laryngeal nerve (RLN) was carefully dissected and central end of the dissected nerve was electrically stimulated. EMG of the contra-lateral Thyro-Arytenoid muscle (TA muscle) to the stimulation was recorded using a hooked-wire electrode inserted through the laryngeal mucosa. EMG of the TA muscle evoked by the stimulation of the ISLN were analyzed with respect to its latency and discharge pattern inter-collicular brainstem transsected. Together with the stimulation of the RLN, vibratory stimuli were given mainly to the subglottic mucosa as conditioning stimuli. The vibratory frequency was changed from 50Hz to 400Hz step-wisely. Following results were obtained. 1. EMG response of the contra-lateral TA muscle to the stimulation of the ISLN showed two different kinds of latency, approximately 8-10msec, and 40-60msec. 2. After inter-collicular brainstem transsection, evoked response of the latter disappeared. This result indicates that the ISLN-RLN reflex loop consisted of more than two routes, different in the number of synaptic junctions. 3. The vibratory stimuli given to the laryngeal mucosa had facilitatory effect on the reflexive EMG response evoked by the stimulation of the RLN. 4. This facilitatory effect of the vibratory stimuli disappeared after topical anesthesia of the laryngeal mucosa. 5. The facilitatory effect on the reflex responses was partially increased depending on the vibratory frequencies applied. In conclusion, vibratory stimuli to the laryngeal mucosa reflexively modulate the activity of the intrinsic laryngeal muscles. PMID- 2213355 TI - [Dilator naris activity in relation to obstructive sleep apnea]. AB - We evaluated the activity of dilator nasalis+ EMG (Electro-Myo-Graphy) and submental EMG during sleep in three patients with obstructive sleep apnea syndrome. Both EMG activities involved periodic changes which proved to be correlated with each other (r = 0.85). Apnea and hypopnea episodes always occurred at the nadir of these periodic changes. The activity of dilator nasalis+ EMG, as well as submental EMG, at the nadir of these periodic changes was significantly lower during REM (Rapid Eye Movement) sleep than non-REM sleep and also significantly lower during severe airway obstruction accompanied by paradoxical movements of thorax and abdomen. The correlation of this EMG activity with SaO2 or the duration of obstructive apnea was more remarkable in submental EMG than dilator nasalis+ EMG in the observed patients. PMID- 2213357 TI - [Investigation of the immune response in tonsillar lymphocytes against streptococci in patients with pustulosis palmaris et plantaris]. AB - The purpose of this study was to clarify the etiological role of immune responses in tonsillar lymphocytes of the patients with pustulosis palmaris et plantaris (PPP). In order to determine their immune response to S. pyogenes T4, S. pyogenes T12, S mitis, S. salivarius, S. sanguis I, S. sanguis II and S. pneumoniae, tonsillar lymphocytes from patients with PPP, CT, and sleep apnea syndrome (control) were cultured with formalinized streptococcal cellular antigens. Blastoid transformation was investigated by [3H] -thymidine uptake, while antistreptococcal antibody production were measured by an enzyme-linked immunosorbent assay (ELISA). The results were as follows. 1. Tonsillar lymphocytes from PPP patients underwent blastoid transformation and accelerated the production of immunoglobulin G following the addition of S. sanguis I, S. sanguis II S. mitis, S. pyogenes T4, and S. pyogenes T12, while those form CT patients and controls did so only with S. pyogenes T4 and S. pyogenes T12. 2. The spontaneous production of specific IgG against various streptococci, including S. sanguis I, S. sanguis II and S. mitis by tonsillar lymphocytes from patients with PPP was already higher than that from CT patients and controls. The specific IgM production was also increased above that in PPP patients without any antigens. 3. S. sanguis I, S. sanguis II and S. salivarius antigens stimulated antigen specific IgM production in tonsillar lymphocytes from PPP patients. 4. The levels of specific IgG production against S. sanguis I and S. sanguis II by tonsillar lymphocytes from PPP patients showed a relationship with the serum levels of the PPP patients. These results suggested that the sensitization of alpha streptococci, especially S. sanguis, in the tonsillar lacunae may lead to the specific production of anti-S. sanguis antibodies in patients with PPP, and these may be involved in the pathogenesis of PPP. PMID- 2213358 TI - [The mechanism of speech perception using multichannel cochlear implant]. AB - The mechanism of speech perception in patients with Australian multi-channel cochlear implant was investigated. 1) Vowel recognition abilities of patients were sufficient with this implant, whereas, consonant recognition abilities were insufficient. 2) Although the cochlear hair cells were functionally damaged, cochlear nerves had the ability to characterize frequency. 3) The signals from the implanted material were very simple compared to those from normal cochlea, however these patients could understand speech well, perhaps due to aid from the central nervous system. PMID- 2213359 TI - [A physiological study of the effect of vibration on reflexive control of cats' larynx: the changes in respiratory phase and the role of internal branch of superior laryngeal nerve]. AB - It is generally considered that the vocal cord is finely and reflexively controlled during phonation. In order to investigate the effect of vibratory stimulation of the subglottis on laryngeal reflex, experiments have been performed using cats' larynx under urethane-chloralose general anesthesia. The effect of vibration was estimated by the latency and the area of integrated EMG of the reflex. The glottic closure reflex was induced by electrical stimulation of the internal branch of the superior laryngeal nerve (ISLN) and electromyogram was recorded from contralateral Thyroarytenoid muscle (TA). When ISLN was stimulated, short latency response (early response) and long latency response (late response) in TA was observed. Maximum responses were obtained during the transitional phase, namely, from inspiration to expiration, especially before the denervation of ISLN from the larynx. This phase was tentatively designated as "phase I", being followed by "phase II", the phase prior to "phase I", as "phase III". Vibratory stimulation (100 or 200Hz, 40 microns), applied to the contralateral subglottic portion as a conditioning stimulation, had no effect on early response but enhanced late response, particularly in phase I. After denervation of ISLN, the vibratory effect on late response became phase independent. Furthermore, when the vibratory frequency was elevated from 100Hz to 350Hz at 50Hz interval in phase I, vibration effect was observed in all frequencies investigated. Maximum effect was obtained at 300Hz. However, after denervation of ISLN, this effect was minimized, and no peak observed. The vibratory effects disappeared soon after local anesthesia of the subglottic mucosa. These results suggest that the activity of the mechanoreceptors to vibration in the subglottic mucosa enhances reflexive contraction of the contralateral TA primarily via the recurrent laryngeal nerve and partially via ISLN, both of which are indispensable for reflexive laryngeal control. It is conceivable that early response is one of the primitive reflexes for the protection of the lower airway, and late response is a sort of more evolved reflexes involved in vibration and respiration during phonation. PMID- 2213360 TI - [Clinical feature of odontogenic maxillary sinusitis--symptomatology and the grade in development of the maxillary sinus in cases of dental maxillary sinusitis]. AB - Odontogenic maxillary sinusitis may occur by draining of an apical dental root abscess into the maxillary sinus. It has been reported that the disease is usually frequent in cases aged of the second and third decades. In most of them, either the first or second molar tooth is assumed to be the origin of the disease. As clinical characteristic symptoms, it is mentioned that an acute unilateral sinusitis appears since the onset and the patient complains a fetid purulent nasal discharge from an early stage. The symptom and its clinical time course in 43 cases with dental maxillary sinusitis, who had been treated by surgical procedures in ENT Clinic in Kitasato University Hospital during past 14 years from 1972 to 1985, were studied retrospectively. The size of the affected maxillary sinus in each case of the disease was measured from the X-ray films. An influence of development of the maxillary sinus to the occurrence of dental sinusitis was discussed by comparing the sizes of the maxillary sinuses in both the group of the disease and the group of simple unilateral maxillary sinusitis. PMID- 2213362 TI - [Application of digital filtering and phase spectral analysis to middle latency response and 40Hz event related potential in central nerve system disorders]. AB - 40Hz event related potential, or 40Hz-ERP, described by Galambos in 1981 has been considered as the useful potential in predicting hearing threshold across the audiometric frequencies. Although 40Hz-ERP was reported by Galambos as the summation of middle latency responses (MLR), its origin has not been clarified. Moreover reports of the clinical use of 40Hz-ERP in patients with the neurological disorders were rare. Therefore, we recorded ABR, MLR and 40Hz-ERP in 35 patients with central nerve system disorders, or CNS disorders, and analysed the relation between central lesions and modality of MLR- or 40Hz-ERP from the view point of phase spectral analysis comparing with the digital filtered waveform analysis. For the phase spectral analysis, synchrony measure method described by Fridman in 1984 was applied to MLR and 40Hz-ERP. Following results were obtained. 1) By the digital filtered waveform analysis, the latencies of Po, Na, Pa and the amplitudes of Po, Na, Pa, Nb were recorded clearly in normal cases. In cases with the central lesions, many of them were revealed reduction of the amplitude of Po, but other parameters were not useful for the detection of CNS disorders because of their wide normal ranges. 2) The parameters of the phase spectral analysis were obtained from 17 records of the normal subjects. The SM (30 + 40 + 50Hz), which is the average of CSM 30Hz, CSM 40Hz and CSM 50Hz, was applied to MLR, and the SM (40 + 80 + 120Hz) was applied to 40Hz-ERP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213361 TI - [A case of hypopharyngeal stenosis caused by late radiation injuries- reconstruction of the hypopharynx with myomucosal tongue flap]. AB - The authors reported a 47-year-old man with hypopharyngeal stenosis caused by late radiation injuries. At the age of ten he underwent irradiation (3000rads) to the neck because of the cervical lymphadenopathy. He had keroid skin change at the age of 19, hypothyroidism since 26, right cervical and brachial plexus neuropathy since 33, and paralysis and papilloma of right vocal cord at 34. And at the age of 41 he underwent tracheostomy owing to laryngeal stenosis. In November 1984 (at age 43) he felt abnormal sensation on the throat but had no dysphagia nor misdiglutition. On November 1987 he had difficulties of swallowing, and could not take anything but fluid. At that time he was diagnosed as hypopharyngeal stenosis. With steroids and antibiotics his difficulties of swallowing were reduced. He experienced the same difficulties on April 1988. Since December 1988 his dysphagia got worse and was not recovered with medication. On May 17 1989, laryngopharyngectomy was performed. At the level of cricoid cartilage hypopharynx was resected. As for the posterior wall, pharynx and cervical esophagus were fixed to prevertebral fascia and anastomosed with end to-end. And antero-lateral defects were reconstructed with myomucosal tongue flap. Postoperatively he could eat orally. On the basis of the experience of this case and the review of the literature the authors conclude that myomucosal tongue flap is one of alternatives for hypopharyngeal reconstruction. PMID- 2213363 TI - [Course of recovery from motor aphasia in four patients with localized lesions in the vicinity of Broca's area]. AB - The neuropsychological signs and prognosis of patients with localized lesions in the vicinity of Broca's area of the left inferior frontal gyrus have been controversial. We studied periodic changes in the neuropsychological signs of four patients who had relatively localized lesions in the vicinity of Broca's area and manifested aphasia of the non-fluent type. The ages of the four patients at the onset were 62, 66, 30 and 37 years. The localized lesions in their brains were the result of brain infarctions revealed by CT scans, and included so-called Broca's center in the left inferior frontal gyrus along with adjacent brain tissue. The neuropsychological signs of the four patients were periodically assessed by means of the standard language test of aphasia (SLTA). In the early stage of aphasia, they had moderate difficulties in speaking to explain test materials or recall words and mild difficulties in reading aloud, repeating and writing words. One year later, most of their neuropsychological signs disappeared except for mild difficulties in speaking fluently and recalling words. It should be noted, however, that all four patients were able to return to their previous occupations one or two years later, because they had recovered from aphasia. Based on the results of this study, we conclude that the neuropsychological signs of Broca's aphasia caused by relatively localized lesions in the left inferior frontal gyrus are mild and largely disappear within one or two years. PMID- 2213364 TI - [Clinico-experimental study on parapharyngeal space invasion of head and neck cancer]. AB - We studied the incidence and mode of development of parapharyngeal space invasion from head and neck cancers by both retrospective examination of our 172 patients and tracing the dynamics of lymph flows to the parapharyngeal space from the hypopharynx, the mesopharynx and the posterior portion of oral cavity. Of the patients examined 23 (13.4%) were found the parapharyngeal invasions (20% in mesopharyngeal cancers, 17.3% in hypopharyngeal cancers, 11.9% in cancers of posterior portion of oral cavity). Parapharyngeal space invasions occur frequently in a direct or indirect way when meso- or hypo-pharyngeal cancers or those of posterior parts of oral cavity invade deeply into the muscle layers and extend to the palatine arch, retromolar region, pharyngoepiglottic fold, lateral base of tongue, or posterior buccal mucosa. These invasions frequently induced such symptoms as trismus (47.8%), swelling of the lateral pharyngeal wall (39.1%), otalgia (34.8%), swelling of infra-auricular and submandibular regions (34.8%, 26.1%) and facial palsy (26.1%). Computed tomography was very useful to the diagnosis of the parapharyngeal space invasion. The parapharyngeal space invasions were successfully removed under a wide surgical field without injuring the important nerves and vessels and with preservation of mandibular function by our modification of Attia's technique. The lymph flow from the hypopharynx was chiefly upward and reached terminally to the parapharyngeal space including the retropharyngeal lymph nodes. The lymph flow from the mesopharynx revealed to drain chiefly into the lower internal jugular nodes. The lymph flow from the posterior parts of oral cavity was divided into anterior and posterior groups. Anterior groups of lymphatic drained into the root of tongue and reached terminally to the vallecula and posterior groups drained into the internal jugular nodes. We should cover all routes for extension of head and neck cancers, including the parapharyngeal space, in the diagnosis and the management of these conditions. PMID- 2213365 TI - [Biological characteristics and prognosis of supraglottic carcinoma--a multivariate correlation analysis of prognosis]. AB - The biological characteristics of supraglottic carcinoma was studied with special reference to the correlations of various biological factors with the prognosis of the lesion. The study included 100 cases of supraglottic carcinoma treated by total laryngectomy in the First Hospital of China Medical University in the period from 1975 to 1978, and 7 factors including histopathological findings observed in serial sections of the whole larynx, clinical findings, clinical course, etc. These factors were statistically analyzed by multiple correlation analysis using the theory of quantification I to determine the relations of these factors to the prognosis, as well as their participations in post operative course. 1. Twenty-seven cases died within 5 years after surgery, and 4 cases could not be followed up. 3 and 5-year survival rates were 79.5% and 72.2%, respectively, as calculated in accordance with the UICC General Rule. 2. Histopathologically 5-year survival rate was 10.0% in cases with poorly differentiated carcinoma, 78.0% in cases with moderately differentiated type, and 83.5% in cases with well-differentiated type. It was remarkably lower in poorly differentiated carcinoma than that in moderately or well-differentiated carcinoma. 3. In cases having dense lymphocyte infiltration associated with lymph follicles in peripheral region of tumor, 5-year survival rate was higher (90.4%) than in the other cases. 4. It was found that, as tumor size increased, 5-year survival rate decreased and the risk of lymph node involvement increased in the neck region. 5. 5-year survival rate was lower (48.5%) in cases with lesion infiltrating the surrounding tissues than in cases with other growth patterns. 6. Multiple correlation coefficient between prognosis and the 7 factors analyzed was 0.766. The important factors were the degree of differentiation (0.735), the degree of lymphocyte infiltration (0.260), the size of primary tumor (0.215), the growth pattern of tumor (0.141) and neck metastasis (0.028). PMID- 2213366 TI - [Clinical electrocochleography in Meniere's disease]. AB - Transtympanic electrocochleography (ECochG) was performed on 137 definite Meniere ears, 29 normal ears and 383 ears with other diseases. The average SP/AP amplitude ratio (SP/AP) was significantly larger than that of normal subjects in the following four disease groups whose causes are thought to be endolymphatic hydrops: 1) definite Meniere's disease, 2) suspected Meniere's disease, 3) delayed endolymphatic hydrops and 4) labyrinthine syphilis. The SP amplitude could not provide any information for a differential diagnosis of endolymphatic hydrops from normal subjects nor from other sensorineural deafness . The upper 99% confidence limit of normal SP/AP using a 100dBSPL click was 0.37 for 29 subjects. In patients with Meniere's disease the relationship between SP/AP and clinical data such as pure tone threshold, audiogram pattern, results of glycerol test and duration of illness from the first vertiginous attack to the test were investigated. In patients with severe hearing loss, the number of those showing SP/AP of greater than 0.37 was much higher than in patients with less severe hearing loss. There were no relationship, however, between SP/AP and duration of illness, or audiogram pattern, or glycerol test. ECochG was recorded before and after intravenous administration of 50 gr of glycerol (10% solution, 500ml), and a significant decrease of SP/AP was found in 21 Meniere ears. However, there were no change of SP/AP after oral administration of 50 gr of glycerol (50% solution, 100ml) and isosorbide (70% solution, 2.0gr/kg of body weight). After endolymphatic sac surgery a decrease of SP/AP of 10% or more was found in 5 ears, an increase of SP/AP in 3 ears, and no change of SP/AP in 3 ears. In the patients showing no change of SP/AP after the surgery, numerical values of vertigo by AAOHNS were higher than in patients showing an increase or a decrease of SP/AP. The results demonstrate the usefulness of ECochG in diagnosis of endolymphatic hydrops and indicate a possibility of monitoring the state of hydrops after administration of glycerol and endolymphatic sac surgery. PMID- 2213367 TI - [Three dimensional culture of human salivary gland using irradiated collagen gel embedding technique]. AB - Embedding culture was performed on normal salivary gland cells from five subjects using 0.2% irradiated collagen gel. Collagen was collected from rat tail tendon and gelatinized at the final concentration of 0.2%. D-MEM added BSA (5mg/ml), insulin (10 micrograms/ml) and EGF (5 micrograms/ml) was used as a serum-free medium. Within the collagen gel, the cells were found to grow in a branch-like pattern, and then to form a lot of radial duct-like structures containing alcian blue positive secretions. Immunohistochemical observation of myoepithelial cells with monoclonal antibody from human mammalian cancer suggested that these cells play an important role in the process of glandular ducts formation. Salivary gland cells being able to grow in collagen gel in a very similar fashion to in vivo condition, the present collagen gel embedding culture is useful for morphological or functional studies on salivary gland cells. PMID- 2213369 TI - Are breast cancer axillary node micrometastases worth detecting? PMID- 2213368 TI - Myofibroblasts. PMID- 2213370 TI - Malignant haemangiopericytoma of lung: a cell culture and ultrastructural study. AB - Malignant haemangiopericytoma was grown in vitro to assess the histogenesis of the tumour. Disaggregated tumour cells maintained in serum-supplemented Waymouth's MB 752/1 medium showed monolayers of homogeneous spindle cells. Post confluent cultures exhibited hillocks or plaques of multilayer growth within which considerable amount of basal lamina-like material and fibrillar matrix were present between cells. Delicate basal laminae were also expressed on cell surfaces facing matrix material. Other consistent features were attenuated cytoplasmic processes, desmosome-like junctions, abnormal mitochondria and a paucity of intracellular filaments. The three-dimensional organization of tumour cells with concomitant expression of differentiated phenotype in vitro has significant implications on the cell of origin and differentiation process of haemangiopericytoma. PMID- 2213372 TI - Fibronectin degradation; an in-vitro model of neutrophil mediated endothelial cell damage. AB - We have observed that fibronectin has a characteristic fibrillar morphology within the extracellular matrix surrounding endothelial cells. This morphology, which is easily recognizable by conventional immunoperoxidase techniques, is disrupted if neutrophils are induced to degranulate on endothelial monolayers. Loss of the fibrillar morphology (degraded fibronectin) is characterized by fragmentation and diffuse spreading of fibronectin over the surface of the endothelial cells. Loss of the normal fibronectin architecture following neutrophil degranulation is more rapid and extensive in endothelium pretreated with Interleukin-1 (IL-1). In addition, there is loss from the fibronectin molecule of a chymotryptic protease-sensitive epitope recognized by a cellular fibronectin specific antibody. Degraded fibronectin is stimulatory for neutrophils, and is likely to induce further fibronectin breakdown. This sequence has the potential to set up an amplification inflammatory loop with neutrophil mediated loss of vascular homeostasis. Alteration of fibronectin architecture is a useful marker of endothelial injury, and has important pathophysiological consequences. PMID- 2213371 TI - Axonal damage in Crohn's disease is frequent, but non-specific. AB - We have attempted to confirm the claim by Dvorak and Silen that 'Crohn's disease is accompanied by a severe and extensive necrosis of gut axons...[which] may serve to differentiate Crohn's disease from other inflammatory conditions'. In this electron microscope study the diagnoses were withheld until the assessment of axonal damage was completed. We assessed the axonal damage in ileostomy biopsies in 13 cases of Crohn's disease, four cases of ulcerative colitis, and two 'controls'. In Crohn's disease we found a mean per cent of abnormal axons of 29.85, in ulcerative colitis of 21.25 per cent, and in the two 'controls' of 12.11 and 10.63 per cent, respectively. The difference between the 13 cases of Crohn's disease and the six cases of non-Crohn's disease is not significant. We found considerable numbers of abnormal, very small axons of uncertain nature but probably related to regeneration following surgery. Including or excluding such axons did not significantly alter the incidence of abnormal axons. We conclude that axonal damage is common in chronic inflammatory bowel disease and is not specifically related to Crohn's disease. PMID- 2213374 TI - Pathological Society of Great Britain and Ireland 161st meeting. 10-13 July 1990, Nottingham. Abstracts. PMID- 2213373 TI - Role of endotoxaemia in the development of hepatic failure following hepatic artery occlusion. AB - The present study was undertaken to examine whether endotoxemia relates to the development of hepatic failure following surgical ligation or embolization of the hepatic artery. A small amount of endotoxin was given immediately or 1 week after hepatic artery ligation in rats, and liver function tests and morphological examination of the liver were performed at 24 h after the administration. Hepatic artery ligation alone or endotoxin administration alone did not induce functional and morphological alteration of the liver. However, when endotoxin was given immediately after hepatic artery ligation, there was an increase in serum transaminase activity and focal hepatocellular necrosis developed. On the other hand, when endotoxin was given 1 week after hepatic artery ligation, the hepatic injury was not induced because of the development of hepatic arterial collaterals. These data suggest that endotoxaemia may be a cause of hepatic failure following hepatic artery occlusion, and that the risk may persist until the establishment of hepatic arterial collaterals. PMID- 2213376 TI - Magnetic resonance imaging appearance of the muscles in childhood dermatomyositis. AB - Documentation of muscle involvement in a child thought to have dermatomyositis may require the performance of invasive procedures such as electromyography and/or muscle biopsy. We describe four patients with dermatomyositis in whom magnetic resonance imaging (MRI) demonstrated the muscle involvement. The involved muscles had increased signal intensity on the T2-weighted images (SE 2500/80) and normal appearance on the T1-weighted images (SE 600/20). The involvement of the muscles was not uniform. There was good correlation between the distribution of muscle involvement by MRI and functional testing. Follow-up MRI scans in patients with favorable outcome demonstrated that the affected muscles had returned to normal signal intensity. Although the MRI findings are not specific, in the proper clinical context they may be helpful in establishing the diagnosis of dermatomyositis. MRI may also be used in establishing an appropriate muscle biopsy site. In addition, MRI may be used for monitoring the progress of the disease. PMID- 2213375 TI - Normalization of plasma arginine vasopressin concentrations when children with meningitis are given maintenance plus replacement fluid therapy. AB - We hypothesized that plasma arginine vasopressin (AVP) concentrations in children with meningitis are appropriate for the children's degree of hypovolemia, even though the concentrations were higher than expected for the serum osmolality. A randomized study was conducted to compare the effect on plasma AVP concentrations of giving maintenance fluid requirements plus replacement of any deficit versus restricting fluids to two thirds of maintenance requirements for 24 hours. Plasma AVP concentrations and serum osmolality were measured before fluid therapy was begun and again after 24 hours. Nineteen children, 2 months to 17 years of age, were studied; 13 had bacterial meningitis (12 with Haemophilus influenzae type b). Ten children (seven with bacterial meningitis) received a mean of 1.42 times the calculated maintenance fluid requirements, and nine (six with bacterial meningitis) were restricted to a mean of 0.65 times maintenance. Children in the maintenance group also received significantly more sodium (mean = 6.3 mEq/kg/24 hr) than children in the fluid-restricted group (mean = 2.0 mEq/kg/24 hr). The two groups were comparable for plasma AVP concentration and serum osmolality before fluid therapy was begun. The plasma AVP concentration was significantly lower after 24 hours of maintenance plus replacement fluids than after fluid restriction (p = 0.005), and the change in AVP concentration correlated with the amount of sodium given (p less than 0.02). This study supports the hypothesis that serum AVP concentrations are elevated in patients with meningitis because of hypovolemia and become normal when sufficient sodium is given to facilitate reabsorption of water by the proximal tubule of the kidney. Patients with meningitis can be given maintenance plus replacement fluids but should be monitored for the development of the syndrome of inappropriate secretion of antidiuretic hormone. PMID- 2213377 TI - Diagnosis of cerebrovascular disease in sickle cell anemia by magnetic resonance angiography. AB - The study of blood flow by means of magnetic resonance techniques has led to a noninvasive magnetic resonance angiography (MRA) technique for imaging large cerebral vessels. Ten children with sickle cell hemoglobinopathy and a history of acute neurologic syndromes were studied with combined parenchymal magnetic resonance imaging (MRI) and MRA. Six had abnormal MRI findings and MRA-defined luminal lesions in the vascular distribution of these parenchymal infarctions. The three children with previous intraarterial angiography had MRA abnormalities that corresponded with vascular lesions on conventional angiograms. Four had normal MRI and MRA findings. We conclude that a combination of MRI and MRA provides a noninvasive screening test for large-vessel disease in this population. PMID- 2213378 TI - Benefits and risks of anemia correction with recombinant human erythropoietin in children maintained by hemodialysis. AB - Ten children with renal failure (age range 2 years 6 months to 18 years 9 months; median 11 years 10 months), maintained by long-term hemodialysis, had successful correction of their anemia after intravenous administration of recombinant human erythropoietin in a dosage escalating every 2 weeks (75 to 150 to 300 to 450 IU/kg/wk). Mean hemoglobin concentration increased from 6.4 +/- 0.9 to 11.5 +/- 1.0 gm/dl. Blood cell counts used to evaluate the correction of anemia were done after dialysis; this was especially important for children less compliant with water restriction. The higher hemoglobin concentration resulted in improvement of the quality of life, a greater tolerance for physical effort (exercise tolerance doubled and the ventilatory anaerobic threshold increased significantly), correction of some subclinical central nervous system abnormalities detected by evoked potentials testing, and reduction of bleeding time. Few side effects were noted; severe hypertension developed in one patient when postdialysis hematocrit was only 28%, and there were two episodes of hypertransaminasemia with no other evidence of liver dysfunction. We conclude that in children with renal failure the use of recombinant human erythropoietin to correct anemia is safe and strongly advisable, because of the resolution of many of the symptoms correlated with anemia. PMID- 2213379 TI - Patterns of food hypersensitivity during sixteen years of double-blind, placebo controlled food challenges. AB - For 16 years the double-blind, placebo-controlled food challenge (DBPCFC) has been used at the National Jewish Center for Immunology and Respiratory Medicine to determine whether adverse reactions to foods do occur in children. The objective of these studies was to explore these reproducible adverse reactions and to characterize them. Although skin testing was performed on all subjects, a history of an adverse reaction to food and to subsequent DBPCFC were the only criteria for entry into this study. Of 480 children studied, 185 (39%) have had positive DBPCFC results. In these 480 children, 245 (24%) of 1014 DBPCFCs showed positive results. Egg, peanut, and cow milk accounted for 73% of the positive DBPCFC reactions, but many foods produced reactions. Skin test results were positive in most children with a positive DBPCFC reaction, but the large number of patients with asymptomatic hypersensitivity limited the accuracy of a positive skin test result alone as a predictor of clinical symptoms during food ingestion. Evaluation of results in this large number of children for a prolonged period revealed reproducible patterns of symptoms, timing, and incriminated foods. Placebo reactions were rare. The procedure was safe. Twelve youngsters with a negative DBPCFC result subsequently had positive reactions to open challenges when large amounts of the challenge food were used. In each of these cases the reactions were limited to areas of direct contact with the food or could be explained by the larger amount of food ingested during the open challenge. Multiple food hypersensitivity has been a rare finding. The DBPCFC should be the "gold standard" for both research and clinical diagnostic evaluations until it is superseded by methods that have yet to be developed. PMID- 2213380 TI - Assessing clinical significance of apnea exceeding fifteen seconds with event recording. AB - Using event recording, we determined how often apnea exceeding 15 seconds in duration was associated with bradycardia and how often patients with apnea resumed breathing spontaneously. Of 1306 documented apnea events exceeding 15 seconds (54 patients), 926 lasted 16 to 20 seconds, 262 lasted 21 to 25 seconds, and 118 exceeded 25 seconds. Of these episodes, 75.3% were isolated and 14.9% were associated with pulse deceleration, 4.4% with irregular transthoracic impedance, and 5.4% with bradycardia. Event recording provided data supporting discontinuation of monitoring in 50 of 54 patients: 36 spontaneously resumed breathing before the auditory alarm and 14 had a decreased incidence of apnea with maturation. Follow-up of 51 patients (three not located) showed that none had subsequent apparent life-threatening events or sudden infant death syndrome. Our results in these older infants and children (median age 6.7 months) provide substantiation that such patients with apnea of less than 20 seconds without bradycardia do not require continued monitoring. Further, these data suggest that in selected older infants, longer isolated apnea may be well tolerated; however, hemoglobin saturation during sleep and the ability to resume breathing after the apnea alarm delay is prolonged should be verified. Our patient population had a wide age range and heterogeneity of diagnoses, and was typically free of symptoms, so these results should not be extrapolated uncritically to premature infants, infants with chronic lung disease, and patients with symptomatic apnea. PMID- 2213381 TI - Acute neurologic dysfunction associated with destructive lesions of the basal ganglia: a benign form of infantile bilateral striatal necrosis. PMID- 2213382 TI - Childhood linear scleroderma "en coup de sabre" with uveitis. PMID- 2213383 TI - Growth failure as a prognostic indicator for progression to acquired immunodeficiency syndrome in children with hemophilia. PMID- 2213384 TI - Long-term outcome of oxandrolone treatment in boys with constitutional delay of growth and puberty. PMID- 2213385 TI - Acquired splenic atrophy in a sibship with the autoimmune polyendocrinopathy candidiasis syndrome. PMID- 2213386 TI - Myocardial infarction leading to sudden death in the Williams syndrome: report of three cases. PMID- 2213387 TI - In vitro and in vivo effect of growth hormone on cytotoxic activity. PMID- 2213388 TI - Widespread multi-tissue deletions of the mitochondrial genome in the Pearson marrow-pancreas syndrome. PMID- 2213389 TI - Pulmonary mechanics in healthy term neonates: variability in measurements obtained with a computerized system. AB - Using a commercially available computer-based analysis of ventilation and esophageal pressure (PeDs), we studied 11 healthy term neonates with serial pulmonary mechanics measurements during the first 3 days of life to determine the intrasubject variability of repeated measurements. Three consecutive pulmonary function tests were obtained before and after repositioning of the esophageal catheter, for a total of six measurements per day in each subject. The daily coefficient of variation for these 11 subjects ranged from 6% to 32% for respiratory rate; 6% to 27% for tidal volume; 3% to 28% for specific dynamic compliance, and 11% to 69% for pulmonary resistance. Repositioning the esophageal catheter did not produce significant differences in measurements of pulmonary mechanics (p greater than 0.05). We conclude that within a given subject, the maximum variability (mean + 2 SD) was 28% for specific dynamic compliance and 56% for pulmonary resistance. These intrasubject variability limits are important when one is interpreting pulmonary mechanics measurements in neonates before and after specific treatment, such as bronchodilators, diuretics, surfactant, or steroids. PMID- 2213390 TI - Mean arterial blood pressure changes in premature infants and those at risk for intraventricular hemorrhage. AB - Bedside microcomputer-derived, minute-to-minute mean arterial pressure (MAP) values during the first 48 hours of life were studied in 100 preterm babies with birth weight less than or equal to 1500 gm. In those babies (n = 72) with no periventricular-intraventricular hemorrhage (PV-IVH) or with grade 1 PV-IVH, the MAP values increased during the study period, with minute-to-minute variation and interval undulation. The MAP values in those with birth weight greater than 1000 gm were higher than in those of lower birth weight. Infants in whom grades 2 to 4 PV-IVH developed (n = 28) had consistently lower MAP values during the study period. Minute-to-minute variability, expressed as the average of the coefficients of variation at 15-minute intervals, did not differ between birth weight groups, nor did they differ between the PV-IVH group and their matched control subjects. However, those with PV-IVH spent a greater percentage of time, with a coefficient of variation greater than or equal to 13% or less than 3%, than their matched control subjects spent (p less than 0.005). This study provides reference data for MAP changes in premature babies. The observed MAP changes in those with PV-IVH lend support to a significant role for MAP alterations in the pathogenesis of PV-IVH. PMID- 2213391 TI - Measurement of progressive cerebral ventriculomegaly in infants after grades III and IV intraventricular hemorrhages. AB - To develop guidelines that might help predict prospectively which infants with severe intraventricular hemorrhage (IVH) would require intervention, we obtained serial cranial sonograms to measure the rate of growth of cerebral ventricular volumes in 48 preterm infants with and without IVH. The infants were divided into three groups: (1) those with no IVH (22 infants), (2) those with IVH with acute ventricular dilation (13 infants), and (3) those with IVH with progressive ventricular dilation requiring intervention (13 infants). The decision to intervene because of progressive ventricular dilation was based on clinical criteria and the subjective assessment of increasing ventricular size on weekly cranial sonograms. The rate of cerebral ventricular volume growth in infants with IVH who needed intervention was greater (4.2 +/- 3.3 ml/day) than that in infants without IVH (0.0 +/- 0.1 ml/day; p less than 0.001) and in infants with IVH and acute ventricular dilation (0.0 +/- 0.2 ml/day; p less than 0.001). Using these data, we generated guidelines for predicting prospectively which infants with IVH and ventricular dilation will need intervention for posthemorrhagic hydrocephalus. The guidelines were then confirmed prospectively in 10 infants. PMID- 2213393 TI - Plasma neutrophil elastase alpha-1-proteinase inhibitor levels in premature neonates with coagulase-negative staphylococcal bacteremia. PMID- 2213392 TI - Neonatal body proportionality and body composition after in utero exposure to cocaine and marijuana. AB - The relationship of maternal use of marijuana and cocaine during pregnancy to measures of neonatal body proportionality and body composition was assessed in a multiethnic sample of 1082 newborn infants. Maternal use of marijuana and cocaine during pregnancy was ascertained by self-report and by an enzyme-multiplied immunoassay technique for screening of urine samples obtained prenatally and again post partum. After each substance was analytically controlled for use of the other and for other potentially confounding variables, detection of marijuana metabolites in maternal urine was associated (p less than 0.05) with depressed mean arm muscle circumference and nonfat area of the arm but not with any measure of neonatal fatness. In contrast, detection of cocaine in maternal urine was associated (p less than 0.05) with decrements of subscapular fat folds and of the fat and nonfat areas of the arm. Although both substances were associated with depressed birth weight, there was no decrement of neonatal ponderal index or of the arm circumference/head circumference ratio in association with exposure to either substance. We conclude that both marijuana exposure and cocaine exposure during pregnancy are associated with symmetric intrauterine growth retardation, but that deficits are in differing compartments of intrauterine growth. These findings suggest that marijuana may retard fetal growth through maternal-fetal hypoxia, whereas cocaine may alter nutrient transfer to the fetus and fetal metabolism. PMID- 2213394 TI - Nebulized albuterol in acute bronchiolitis. AB - In a double-blind, placebo-controlled trial, 40 infants between 6 weeks and 24 months of age who had a first episode of wheezing and other signs and symptoms of bronchiolitis were randomly assigned to receive either nebulized albuterol (0.15 mg/kg/dose) or placebo (saline solution) for two administrations 1 hour apart. The albuterol therapy resulted in a significantly greater improvement in the accessory muscle score (decreases 0.70 vs decreases 0.30; p = 0.03), oxygen saturation (increases 0.71% vs decreases 0.47%; p = 0.01) after one dose, and in the accessory muscle score (decreases 0.86 vs decreases 0.37; p = 0.02), respiratory rate (decreases 19.6% vs decreases 8.0%; p = 0.016), and oxygen saturation (increases 0.76% vs decreases 0.79%; p = 0.015) after two doses of the drug. The response to therapy was similar in infants younger and those older than 6 months of age. The heart rate rose slightly more in the albuterol group (increases 7.76 from baseline) versus the placebo group (decreases 6.79). There were no other side effects of the treatment. Of the 34 children from whom nasal specimens were obtained by swab for viral identification, 24 had positive test results (21 for respiratory syncytial virus, 1 for parainfluenza, 1 for paramyxovirus, and 1 for influenza A). We conclude that nebulized albuterol constitutes a safe and effective treatment of infants with bronchiolitis. PMID- 2213395 TI - Treatment of Kawasaki syndrome: a comparison of two dosage regimens of intravenously administered immune globulin. AB - Because intravenously administered immune globulin (IVIG) is effective in reducing the incidence of coronary artery aneurysms in Kawasaki syndrome when given at a dose of 400 mg/kg daily for 4 days, we undertook a multicenter clinical trial comparing two dosage regimens of IVIG. Patients were randomly assigned to receive IVIG at either 400 mg/kg daily for 4 days (22 patients) or 1 gm/kg as a single dose (22 patients). All patients received aspirin therapy, and all were enrolled within 7 days of onset of fever. The presence of coronary artery aneurysms was evaluated by means of two-dimensional echocardiography before infusion; at days 4 to 6, 14 to 21, and 42 to 49 after infusion; and at 1 year. Coronary artery aneurysms were detected in 3 of the 44 patients, including one patient receiving 400 mg/kg and two patients receiving 1 gm/kg (p value not significant). No giant aneurysms were detected. No major side effects occurred with either dosage regimen. Patients receiving the 1 gm/kg dose had a faster resolution of fever and were discharged from the hospital approximately 1 day sooner than the 400 mg/kg group (p = 0.01). Although the relatively small sample size in this trial does not allow for a more definitive statement regarding the occurrence of coronary artery aneurysms, it appears that the 1 gm/kg dose is associated with a more rapid clinical improvement and a shorter hospital stay. PMID- 2213396 TI - Ibuprofen suspension in the treatment of juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group. AB - Ninety-two children with juvenile rheumatoid arthritis were randomly assigned to treatment in a multicenter, double-blind, 12-week trial designed to compare the efficacy and safety of a liquid formulation of ibuprofen at a dosage of 30 to 40 mg/kg/day versus those of aspirin at a dosage of 60 to 80 mg/kg/day. No significant intergroup differences in response rates or in the amount of improvement in articular indexes of disease activity were observed. More children treated with aspirin discontinued treatment early because of adverse reactions. After this trial, 84 additional patients with juvenile rheumatoid arthritis entered a 24-week, multidose (30, 40, and 50 mg/kg/day), open trial of ibuprofen suspension. Favorable response rates for the three groups were similar, and continued improvement was observed throughout the 24-week period. A dose-response relationship was observed with respect to adverse reactions of the upper gastrointestinal tract. We conclude that ibuprofen suspension is an effective nonsteroidal antiinflammatory drug and that its tolerability in children is acceptable. PMID- 2213397 TI - Safety and efficacy of methotrexate therapy for juvenile rheumatoid arthritis. AB - Twenty-nine children with juvenile rheumatoid arthritis were studied to determine the safety and efficacy of methotrexate therapy. The initial dose of methotrexate averaged 7.1 mg/m2/wk and was given as a single, oral weekly dose or as three divided doses, each separated by 12 hours. Current antiinflammatory medications were continued; 25 of 29 children had had lack of efficacy, and 8 of 29 had toxic effects, with one or more prior drugs such as intramuscularly or orally administered gold, hydroxychloroquine, or D-penicillamine. Intolerable corticosteroid dependency or toxic effects were present in 18 of 29 cases. Methotrexate-treated patients were examined monthly; minimum treatment duration required to assess efficacy and toxicity was 6 months. The range of treatment duration was 8 to 39 months (mean 18.5 months). Efficacy was assessed by comparing pretreatment versus posttreatment fever and rash, swollen-joint counts, articular indexes, duration of morning stiffness, functional class, hemoglobin levels, and platelet counts. Treatment with methotrexate effectively controlled fever and rash in 83% of children with systemic juvenile rheumatoid arthritis, reduced morning stiffness by 63%, eliminated recalcitrant joint restriction in 48%, and reduced numbers of swollen joints and swelling indexes by 46% and 52%, respectively. No significant toxic effects were observed. Juvenile rheumatoid arthritis of long duration, or with major erosions, was more likely to be refractory to methotrexate therapy. We recommend earlier consideration of methotrexate in place of other slow-acting antirheumatic drugs for juvenile rheumatoid arthritis not responding well to usual therapy. Future studies should address potential methotrexate toxic effects in the lungs and reproductive system, as well as outcome after discontinuation of methotrexate treatment. PMID- 2213398 TI - Naproxen-induced pseudoporphyria: a distinctive photodermatitis. AB - A distinctive photodermatitis developed in 22 children who had been receiving naproxen for prolonged periods. The eruption was marked by erythema, vesiculation, or increased skin fragility characterized by easy scarring of sun exposed skin. Results of biochemical studies for porphyria were normal, and other causes of photosensitivity were believed to be unlikely. Of the 22 patients, 21 had juvenile rheumatoid arthritis; one patient had systemic lupus erythematosus. Twenty of the patients had fair skin and blue eyes. In each case, all findings except scarring resolved when naproxen was discontinued. Attention must be paid to complaints suggesting photosensitivity in children receiving naproxen. PMID- 2213399 TI - Evaluation of a rapid latex-particle agglutination-inhibition screening assay for cocaine in urine. PMID- 2213400 TI - Accuracy of glucose reflectance meters during the neonatal period. PMID- 2213401 TI - Brain maturation and magnetic resonance imaging. PMID- 2213403 TI - The molecular revolution and nematode parasitology: yesterday, today, and tomorrow. PMID- 2213402 TI - Influence of antidiarrheal and antimicrobial medications on the hemorrhagic colitis associated with hemolytic-uremic syndrome. PMID- 2213404 TI - Tyrosine-derived cross-linking amino acids in the sheath of Haemonchus contortus infective larvae. AB - The sheath or second-molt cuticle (2M) was isolated from in vitro exsheathed Haemonchus contortus infective larvae (L3[2M]). Acid hydrolysates of 2 mercaptoethanol (2ME)-soluble and 2ME-insoluble cuticular proteins were analyzed by high performance liquid chromatography for tyrosine-derived cross-linking amino acids. Dityrosine and isotrityrosine were identified by their chromatographic behavior, absorbance spectra, and other chemical characteristics in both the 2ME-soluble and 2ME-insoluble fractions. Dityrosine and isotrityrosine were found in greater amounts in the 2ME-insoluble proteins. When intact 2M cuticles were labeled with 125I prior to acid hydrolysis, radiolabel was recovered in tyrosine but not dityrosine or isotrityrosine indicating that the tyrosine cross-links are not susceptible to iodination in the intact protein. The results are consistent with a hypothesis that tyrosine-derived cross-links are important components of H. contortus 2M cuticular proteins. PMID- 2213405 TI - Identification of the secreted neutral proteases from Anisakis simplex. AB - Ingestion of larval nematodes (family: Anisakidae) can cause the human disease known as anisakiasis. After ingestion, Anisakis larvae can be invasive, penetrating host stomach or intestinal wall. Observation of larvae penetrating the tissue layers of human stomach in vitro by SEM showed tunnels and burrows were formed in the mucosa and submucosa. Based on these observations, we hypothesized that secreted proteases may be involved in the degradation of host tissue macromolecules to allow tunnel formation. Using a model of connective tissue extracellular matrix (ECM), we found that as few as 5 Anisakis simplex larvae could degrade approximately 25% of the ECM in a 16-mm culture well in 24 hr. Further characterization of the secreted proteases using synthetic peptide substrates and inhibitors revealed that there were 2 classes of proteases present: a metallo aminopeptidase and a trypsinlike serine protease. Extracts of Anisakis larvae contained a 25-kDa protease that was recognized by rabbit anti rat trypsin antibody on western blots. This suggests that there is structural as well as functional similarity between the Anisakis trypsin and vertebrate trypsins. PMID- 2213406 TI - Growth characteristics in axenic and cell cultures, protein profiles, and zymodeme typing of three Trypanosoma cruzi isolates from Louisiana mammals. AB - Rates of trypomastigote adherence, interiorization, amastigote division in, and trypomastigote release from Vero cells were measured for Trypanosoma cruzi isolates from a dog (Tc-D), opossum (Tc-O), and an armadillo (Tc-A) from Louisiana. Because the Tc-O and Tc-A (wild isolates) trypomastigotes became interiorized rapidly, the media were quickly depleted of trypomastigotes thus reducing the numbers available to adhere to cells. In contrast, the Tc-D trypomastigote interiorization rate was slower. Intracellular amastigote division rate was slower for the Tc-D than the wild isolates. The Tc-D trypomastigotes were released from cells approximately 2 days later than wild isolate trypomastigotes, but twice the number were released. Growth rate for Tc-D epimastigotes in liver infusion tryptose media was faster than that of wild isolates. The doubling times for Tc-D, Tc-O, and Tc-A were 48.0, 69.0, and 67.4 hr, respectively. Soluble parasite extract was produced from epimastigotes of each isolate by freeze/thawing, sonication, and high-speed centrifugation. Proteins were separated on an SDS-PAGE slab gel and stained with Coomassie blue. Although similar bands were present in each preparation, the general pattern of staining was similar only between the Tc-O and Tc-A preparations, which showed some differences from the Tc-D preparation. Each isolate was zymodeme typed using 5 enzymes in lysates produced from epimastigotes of each isolate. Enzymes were separated electrophoretically and stained. Wild isolates showed similar patterns as zymodeme 1 reference stock, whereas the Tc-D isolate produced a pattern that did not resemble any of the reference stocks examined. PMID- 2213407 TI - Cryptobia cataractae from the blood of Semotilus atromaculatus: structure and division in the fish. AB - A cryptobiid was found in the blood of 2 of 9 Semotilus atromaculatus from a tributary of the Saugeen River in Ontario, Canada. Blood inoculation produced an infection in 2 uninfected S. atromaculatus but not in any Oncorhynchus mykiss, Catostomus commersoni, or Carassius auratus. The flagellate was identified as Cryptobia cataractae, based on host restriction. Cryptobia cataractae occurred as slender and broad forms (body width 3.0-8.7 microns). The length of the anterior flagellum was equal to body length, whereas that of the free recurrent flagellum was half body length. Cryptobia cataractae divided by equal binary fission that produced elongate, slender daughter cells. PMID- 2213408 TI - Electrophoretic characterization of Giardia isolated from humans, cattle, sheep, and a dog in Switzerland. AB - Nine isolates of Giardia lamblia from humans, cattle, sheep, and 1 dog were compared by employing agarose gel isoenzyme electrophoresis and isoelectric focusing of total soluble cell protein on polyacrylamide gels. The banding patterns of the 14 enzymes examined showed remarkable similarities among the Swiss Giardia isolates. This was true also of the total soluble trophozoite proteins. The electrophoretic mobilities of most enzymes and other proteins obtained for the Swiss isolates were the same as those of 2 isolates from humans in other geographical areas, the WB and the Portland-1 strains. Only the human isolate CH-H2 could clearly be distinguished from all other isolates analyzed. The great biochemical similarities observed among the Swiss isolates contrast with the extensive heterogeneity previously demonstrated for G. lamblia by other investigators who used similar analytical techniques. These data are consistent with recent transmission studies of Giardia and suggest that in Switzerland domestic animals may serve as a reservoir of human Giardia infections and that cross-transmission between humans and animals is likely to occur. PMID- 2213409 TI - Developmental and age-related changes in proteins in the female reproductive tract of Heligmosomoides polygyrus (Nematoda). AB - Proteins in the female reproductive tract of Heligmosomoides polygyrus at days 8, 16, 35, 90, and 140 postinfection (PI) were examined using polyacrylamide gel electrophoresis. Sixteen-day-old and 140-day-old worms also were examined histochemically. Egg production of these worms was assessed for each age group. In analyzing proteins using electrophoresis, the reproductive tracts were separated into 3 sections: the tip, or anteriormost part of tract, containing oogonia; the middle region, containing developing oocytes; and the posterior region, containing the uterus with fertilized eggs. Three major reproductive tract proteins were identified as having molecular weights of greater than 140 kDa, 115 kDa, and 82 kDa. These were found in all parts of the reproductive tract from worms of all ages except those at 8 days PI (which are too young to produce eggs) and are believed to be yolk proteins. Four low molecular weight proteins (L1-4) are believed to be nucleoproteins. L4 was absent from the posterior section of the reproductive tracts and L3 was limited to the posterior sections and may be associated with sperm stored in the uterus. Of 5 high molecular weight proteins the second heaviest, designated H2, appeared to be relatively more concentrated in the posterior sections of the reproductive tract. An 85-kDa protein was limited to the tip and middle sections of reproductive tracts. Histochemical tests on sectioned H. polygyrus showed strong positive reactions for protein in cytoplasmic granules in developing oocytes and in eggs of younger worms (16 days) but a reduced reaction in older worms (140 days). Strains for collagen showed a slight positive reaction in and between developing oocytes and a strong reaction in the egg shells. Stains for nucleoproteins particularly reacted with sperm stored in the uterus, and slightly reacted with fertilized eggs and the nucleoli of the intestinal and ovarian epithelium. Egg production by H. polygyrus increased to 123 eggs/female/day by 16 days PI but declined from 121 eggs/female/day at 35 days PI to 64 eggs/female/day in worms 140 days old. Electrophoresis indicated no loss in the different types of proteins in the reproductive tract of older worms, but histochemistry and protein content assays suggest that older worms that produce fewer eggs contain a relatively smaller amount of protein in the female reproductive tract. PMID- 2213410 TI - The Peruvian III strain of Plasmodium brasilianum in Saimiri sciureus boliviensis monkeys. AB - A strain of Plasmodium brasilianum was isolated from a naturally infected Saimiri monkey from Peru and subsequently passaged to 21 splenectomized Saimiri sciureus boliviensis monkeys. Nine of 12 attempts to transmit infection by sporozoite inoculation were successful with prepatent periods ranging from 23 to 41 days. Gametocytes were infective to Anopheles freeborni, Anopheles stephensi, Anopheles dirus, Anopheles maculatus, and Anopheles gambiae mosquitoes. The strain demonstrated a high level of resistance to cure with chloroquine. PMID- 2213411 TI - Short-tailed shrews as reservoirs of the agents of Lyme disease and human babesiosis. AB - To determine whether short-tailed shrews (Blarina brevicauda) serve as reservoir hosts for the Lyme disease spirochete (Borrelia burgdorferi) and the agent of human babesiosis (Babesia microti), we examined nymphal ticks that had fed as larvae on shrews collected from 3 enzootic sites in coastal Massachusetts for evidence of infection by either or both of these agents. Xenodiagnosis indicated that 11 of 14 shrews were infected by B. burgdorferi. One of 3 piroplasm-infected shrews also infected ticks with B. microti. In a site where the piroplasm is endemic, 11 of 17 shrews showed patent parasitemias by thin blood smears. Of these, 4 had parasitemias exceeding 40%. Few immature ticks infested shrews, however, suggesting that B. brevicauda, although abundant in some endemic sites and serving as a competent reservoir, would contribute minimally to the population of infected nymphs. PMID- 2213412 TI - Trickle infections with Nippostrongylus brasiliensis in rats: larval migration through the lungs. AB - The effects of exposure of rats to repeated low-level (trickle) infections with Nippostrongylus brasiliensis were assessed by measuring intestinal and lung worm burdens. Worm recoveries from the intestine, made during a period of trickle infection in rats of different ages, showed a virtually complete rejection of intestinal worms in old rats and a partial rejection in young rats. Recoveries from lungs were made in young rats after challenge infection with 500 third-stage (L3) larvae, given after a 2- or 4-wk period of sensitization, during which rats were infected with 10 or 20 doses of 25 larvae. Such trickle infections elicited a strong host response to a challenge infection, manifested by low recoveries of larvae and an increased duration of larval retention in lungs. In another group of rats sensitized by a single dose of 250 L3 larvae, the recovery of larvae from challenge infection and their clearance from the lungs were similar to these observed in rats uninfected prior to challenge. The effect of trickle infections on preintestinal stages was most pronounced and consistent in rats exposed to larvae the greater numbers of times and over the longest period. PMID- 2213413 TI - Genetic analysis of the relationship between interleukin production and worm rejection in Trichinella spiralis-infected inbred mice. AB - The production of interleukin 1 (IL-1), IL-2, and IL-3 by peritoneal macrophages, mesenteric lymph node (MLN), or spleen cells from inbred strains of mice infected with Trichinella spiralis was examined. The mice belonged to the worm rejection phenotypes previously characterized as strong (NFS), intermediate (C3H, BUB, DBA/1, SWR, CBA, etc.), or weak (B10.Q, B10.BR, etc.). Strong responder NFS mice produced approximately twice as much IL-1 as intermediate responder C3Heb/Fe or weak responder B10.BR mice. IL-3 production varied slightly among strains but did not show any relationship to the phenotype of rejection (highest: C3Heb/Fe, B10.BR; lowest: B10.Q). Of 16 strains of inbred mice and 6 F1 hybrid crosses assessed, marked variations occurred in IL-2 production from MLN cells in response to T. spiralis antigen challenge in vitro. When 16 mouse strains were compared IL-2 production ranged from 5.1 units/ml (A/J) to 29.8 (NFS). Variations in IL-2 production among mouse strains did not relate directly to MHC haplotype, and the capacity of an individual strain to release IL-2 or IL-3 did not correlate with adult worm rejection phenotype. Genetic linkage studies proved that the gene(s) regulating IL-2 production in T. spiralis infection were not linked to the gene(s) regulating adult worm rejection. Regression analysis showed a weak correlation of high IL-2 production with weak worm rejection suggesting that IL-2 production or an associated process is a negative factor in primary worm rejection. PMID- 2213414 TI - A medium for the continuous cultivation of bloodstream forms of Trypanosoma lewisi at 37 C. AB - Trypanosoma lewisi has been maintained continuously at 37 C for more than 2 yr in Iscove's modified Dulbecco's medium with 10% fetal calf serum and a feeder layer of rat fibroblasts. In this medium the continuously reproducing hematozoic culture forms resemble bloodstream forms of T. lewisi in that they appear morphologically similar in Giemsa-stained preparations examined by light microscopy and have a surface coat that is absent in culture forms grown at ambient temperatures, when examined by electron microscopy. To determine whether these hematozoic culture forms also are similar functionally to bloodstream forms, comparative tests of the 2 forms were made of infectivity for the natural rat host, growth in vitro in the described culture medium, sensitivity to inhibition of reproduction by the rat antibody ablastin, and agglutinability by the 2 trypanocidal antibodies produced during a natural course of infection in the rat. Initially, differences between the 2 forms were minor, but after 16 mo in vitro greater differences began to emerge. Most marked was a reduction in infectivity by 22 mo, although sensitivity to ablastin, the single most important characteristic of bloodstream forms of T. lewisi, was still appreciable at this time. Nevertheless, despite this limitation, the culture system described supports hematozoic culture forms of T. lewisi for a considerably longer time than has been reported thus far. PMID- 2213415 TI - Axenic culture and characterization of Giardia ardeae from the great blue heron (Ardea herodias). AB - Trophozoites of Giardia ardeae were obtained from the great blue heron (Ardea herodias) and established in axenic culture using the TYI-S-33 medium. The generation time in culture for G. ardeae was 22-25 hr, which was 3-fold longer than for Giardia duodenalis (WB strain). A morphological comparison of trophozoites in the original intestinal isolate to those grown in culture revealed that they were identical for the following characteristics: a pyriform shaped body, a ventral adhesive disc with a deep notch in the posterior border, teardrop-shaped nuclei, pleomorphism in median body structure ranging from a round-oval appearance (Giardia muris type) to that of a clawhammer (G. duodenalis type), and a single caudal flagellum on the right side (as viewed dorsally) with the left one being rudimentary. Analysis of the chromosomal migration patterns was performed by orthogonal-field-alternation gel electrophoresis and demonstrated that the pattern for G. ardeae was distinctly different from that for G. duodenalis (Portland 1-CCW strain). Bacterial symbionts were seen attached to trophozoites in the original isolate but could not be detected in cultured trophozoites using scanning electron microscopy, fluorescence light microscopy using the Hoechst 33258 dye for DNA localization, or by standard microbiological techniques using nonselective media for growing aerobic or anaerobic bacteria. This study demonstrated that avian-derived Giardia could be grown in axenic culture; based on morphological criteria and chromosomal migration patterns, that G. ardeae should be considered a distinct species; and that rationale for determining Giardia spp., based on median body structure alone, should no longer be considered adequate for classification at the species level. PMID- 2213416 TI - Escape of rediae from miracidia of Philophthalmus megalurus and Philophthalmus gralli during in vitro culture. AB - Miracidia of the eyeflukes Philophthalmus megalurus and Philophthalmus gralli contain a preformed larval stage that was identified as a redia by electron microscopy and, on living forms, by the presence of ambulatory buds and an oral opening. This redial stage escaped and actively moved about when the miracidium stopped swimming in pond water. No redial escape was observed in NaCl solutions even though miracidia became immobile, but escape was noted in Hanks' balanced salt solution (HBSS) after 7 hr of exposure. When miracidia were placed in RPMI 1640 and Eagle's minimum essential medium, rediae escaped much earlier than in pond water and HBSS. Redial escape in vitro will provide a good source of material to initiate cultures of this larval stage. PMID- 2213417 TI - Transmission of Plasmodium fragile to Saimiri monkeys. AB - Saimiri monkeys from Bolivia and Guyana were infected with the Nilgiri and Ceylon strains of Plasmodium fragile. Of 20 attempted sporozoite transmissions of the Ceylon strain involving 11 splenectomized Saimiri sciureus boliviensis, only 8 were successful, 2 by mosquito bite and 6 by intravenous injection of sporozoites dissected from salivary glands. Prepatent periods ranged from 18 to 30 days with a mean of 25.8 days. PMID- 2213418 TI - Neospora caninum (Apicomplexa) in an aborted equine fetus. AB - Tachyzoites of Neospora caninum were found in sections of lung of an equine fetus aborted 2 mo before term. Individual tachyzoites were approximately 3-5 x 2-3 microns, divided by endodyogeny, and stained positively with anti-N. caninum serum but not with anti-Toxoplasma gondii serum. Toxoplasma gondii antibody was not found in the mare's serum. This is the first report of N. caninum in a horse and indicates that N. caninum can be transmitted transplacentally in equids. PMID- 2213419 TI - Prevalence of Trypanosoma theileri in Louisiana cattle. AB - Cattle (from 5 sites in Louisiana) were examined by blood culture for the presence of Trypanosoma theileri. A prevalence of 81% was found in the 291 cattle examined. A greater number of beef cattle (93%) than dairy cattle (73%) was infected. Differences in prevalence in cattle from different regions of the state were not noted. PMID- 2213420 TI - Domestic sheep as a rare definitive host of the large American liver fluke Fascioloides magna. AB - Two domestic sheep were inoculated orally with 250 metacercariae of Fascioloides magna. One sheep died 4 mo after inoculation and 22 immature F. magna were recovered. The second sheep remained healthy and was killed 8 mo after inoculation. Ten mature F. magna were recovered from hepatic parenchyma, and eggs of F. magna were observed in areas of the liver where flukes resided and from feces. Although F. magna is almost always lethal to sheep, this sheep was a rare definitive host. PMID- 2213421 TI - Isolation of Leishmania mexicana from Neotoma micropus collected in Texas. AB - A female Neotoma micropus infected with Leishmania was collected in Zavala County, Texas, on 15 January 1990. The infection was limited to lesions at the bases of the ears, and the parasite grew readily in Schneider's Drosophila medium supplemented with 20% fetal bovine serum. Isozyme analysis determined the parasite to be Leishmania mexicana. PMID- 2213422 TI - Schistosoma intercalatum from Cameroon and Zaire: chronobiological differentiation of cercarial emergence. AB - An experimental study of the cercarial emergence rhythm was conducted to compare 2 geographical strains of Schistosoma intercalatum from Cameroon and Zaire. For the Cameroon strain, the peak emergence time was between 1300 hr and 1400 hr, and the mean emergence time was 1359 hr. For the Zaire strain, the peak emergence time was between 1200 hr and 1300 hr, and the mean emergence time was 1213 hr. These results were shown to be significantly different by statistical analysis. Thus, the chronobiology of the emergence rhythms of the cercariae seems to be an additional marker to estimate the genetic variability of this species and to characterize the 2 strains. PMID- 2213423 TI - Electrophoretic evidence concerning the relationship between Haplometrana and Glypthelmins (Digenea: Plagiorchiiformes). AB - Analysis of genetic data from a multilocus allozyme study, using cellulose acetate gel electrophoresis, of 2 trematode species, Glypthelmins californiensis Stafford, 1905, and Haplometrana intestinalis Lucker, 1931, from Rana aurora and Rana pretiosa, yielded a Nei's genetic distance coefficient between parasites of 0.70 +/- 0.10. This amount of genetic divergence is characteristic of comparisons between congeneric rather than intergeneric trematode species and supports the conclusion, corroborated by morphology and life history, that H. intestinalis is more closely related to some members of Glypthelmins than to any other species. PMID- 2213425 TI - Infectivity of Trichinella pseudospiralis isolated from carrion. AB - The reproductive capacity index for Trichinella pseudospiralis infective larvae was similar for worms isolated from mouse carcasses on the day upon which mice were killed (day 0: 104.4 +/- 18.6 [mean +/- SD]) and on day 5 following mouse death (106.1 +/- 23.6), but was reduced for worms recovered from carcasses on day 10 postkill (PK: 22.7 +/- 5.7). Larvae isolated from mouse carcasses held at 24 C after day 10 PK were not infective. The percentage of viable worms (tightly coiled or moving) isolated from carrion was similar on days 0 and 5 PK but had declined to 40.4% by day 10 PK and showed a further reduction to 11.8% for worms isolated from carrion on day 15 PK. Viable worms were not recovered from carcasses after day 15 PK. PMID- 2213424 TI - Egg and miracidium of Hirudinella ventricosa (Trematoda: Hirudinellidae). AB - It is reported for the first time that Hirudinella ventricosa releases eggs in strings, each string containing active spermatozoa and numerous oval, thick shelled, translucent eggs measuring 40-42 x 28-30 microns. Each egg contained a fully developed miracidium with an anterior crown of spines. PMID- 2213426 TI - In vitro attenuation of Cryptobia salmositica and its use as a live vaccine against cryptobiosis in Oncorhynchus mykiss. AB - The present communication reports on the attenuation of a pathogenic hemoflagellate, Cryptobia salmositica Katz (Sarcomastigophora: Kinetoplastida) and its use as a live vaccine against cryptobiosis. The parasite was attenuated by continuous in vitro culture (at 10 C for 55 wk) in minimum essential medium. Attenuated (culture) forms are morphologically similar to virulent (blood) forms. They are however more slender and have a shorter anterior flagellum and a smaller nucleus and kinetoplast. The attenuated form returned to its normal size and multiplied when inoculated into naive Oncorhynchus mykiss. It produced a low parasitemia but did not cause disease (e.g., no exophthalmia or anemia) in fish. At four wk after infection, the vaccinated fish were challenged with the virulent parasite. They were protected from the disease, whereas the control (naive) fish, infected with only the virulent parasite, had the usual clinical signs (e.g., anemia, exophthalmia). No parasite was detected in any of 10 vaccinated fish at 22 wk after challenge with the virulent parasite. However, 5 of 9 fish infected with culture forms and 6 of 9 fish infected with blood forms still had detectable parasites at 26 and 22 wk after infection, respectively. PMID- 2213427 TI - Application of improved standardization methods and instrumentation in the USP particulate test for SVI. AB - The USP (788) requirement for particulate matter in small volume injections (SVI) became effective January 1, 1986. The standardization component of the requirement is time-consuming and open to subjective interpretation. Current generation light obscuration (LO) counters offer many advantages over those available when (788) was implemented. Significant improvements may be made to the requirement by optimizing the counter standardization procedure and making provisions for use of newer instrumentation. Key improvements to (788) suggested by our experience with the SVI test method include: (1) revision of the requirement to include a time-effective stand-alone standardization procedure; (2) provision for use of currently marketed LO counter systems; (3) development of new standard materials including a count standard; and, (4) deletion of the present requirement for validation of LO counts by microscopy. Significant user advantages accruing to an improved methodology and the use of new instrumentation will include decreased time spent in standardization, lower variability of data between different laboratories, and less instrument down time. PMID- 2213428 TI - Depyrogenation by endotoxin removal with positively charged depth filter cartridge. AB - Bacterial endotoxin, a major quality of parenteral pharmaceuticals, is negatively charged lipopolysaccharide (LPS). A depth filter chemically modified to carry positively charged functional groups is applied to remove endotoxin from aqueous solutions and buffers through charge interaction. The environmental conditions, such as pH and electrolytes, known to affect the efficiency of endotoxin removal by the filter were studied. The charge character of the solid filter was titrated potentiometrically. Other factors such as pyrogen concentration and flow rate were also studied. The effectiveness of depyrogenating the aqueous solution by endotoxin removal through charge interaction with the depth type filter cartridge is fully demonstrated. An optimized cartridge performance can be achieved by following the conditions illustrated in this report. A multi-cell cartridge capable of processing bulk volume of fluid at or over 5 GPM makes it an effective depyrogenating device for the pharmaceutical industry. PMID- 2213430 TI - Rapid/automated ID methods survey. PDA Microbial ID Task Force. Parenteral Drug Association. PMID- 2213429 TI - The influence of charged lipids on the flocculation and coalescence of oil-in water emulsions. I: Kinetic assessment of emulsion stability. AB - The influence of various negatively charged lipids on the stability of phospholipid stabilized oil-in-water emulsions in the presence of varying concentrations of calcium chloride was examined by a measurement of the changes in the turbidity of the emulsion over time. The data were described well by the following equation: (Ai - A) = (Ai - A0) exp(-kt) where Ai is the maximum spectrophotometric absorbance achieved in the system, A is the absorbance at time t, A0 is the absorbance at the start of the experiment and k is the flocculation or coalescence rate constant. Plots of k and Ai/A0 vs. concentration of Ca++ provided an indication of the rate and extent of emulsion flocculation/coalescence, respectively. The sodium salts of phosphatidic acid (SPA) and oleic acid (SO) increased the critical flocculation concentration of calcium while sodium phosphatidylinositol (SPI) and sodium phosphatidylserine (SPS) had no effect on the critical flocculation concentration compared to the control emulsion. The addition of all lipid salts increased the rate of flocculation compared to the control emulsion, however, emulsions containing SPI demonstrated the highest values of k. In contrast, emulsions containing SO coalesced to the largest extent, as indicated by large values of Ai/A0. Systems containing charged phosphatides regained some stability in higher concentrations of Ca++ while those containing oleate were comparatively more unstable up to 20 mM Ca++. Based upon the results of the present studies, it appears that phosphatidic acid is the most important fraction of the anionic phosphatides in stabilizing an emulsion in the presence of calcium ion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213431 TI - Report on survey of current industry gowning practices. PDA Gowning Task Force. Parenteral Drug Association. PMID- 2213432 TI - Current regulatory issues regarding sterile products. PMID- 2213434 TI - Fundamentals of a microbiological environmental monitoring program. Technical Report No. 13. PDA Environmental Task Force. PMID- 2213433 TI - The production of pharmaceutical grades of water using continuous deionization post-reverse osmosis. AB - Continuous deionization (CDI) devices to purify water have recently become available. CDI and reverse osmosis (RO) equipment can form the key elements of water treatment trains that produce ultrapure water, without the need for the chemical regenerants associated with batch ion-exchange processes. CDI systems used as downstream polishers of RO product water have been found to be effective for the removal of trace ionic contaminants. Recently, CDI technology was extended, and devices are now capable of removing dissolved carbon dioxide without the requirement of pH adjustment. Examples from a number of installations are provided. CDI systems have been found to reduce the levels of total oxidizable carbon as well. Field experiences are provided and discussed. RO/CDI systems can be maintained to provide product water with low levels of bacteria and pyrogens. The results of a nine-month study of a system designed to produce pharmaceutical grade water are provided. PMID- 2213435 TI - Electron cytochemical studies of Cryptococcus neoformans grown on uric acid and related sources of nitrogen. AB - Cells of Cryptococcus neoformans grown on xanthine or urate as the sole sources of nitrogen produced numerous, single membrane-bound organelles, deemed to be microbodies. Electron images of these structures showed positive cytochemical staining for catalase and alpha-hydroxy acid oxidase, known marker enzyme activities for microbodies. Microbodies in xanthine and urate-grown cells were cytochemically reactive for the presence of the hydrogen peroxide-producing xanthine and urate oxidases. Molybdenum and phosphorus (elements associated with the cofactor common to nitrogen scavenging enzymes) were detected in the substrate-induced microbodies by X-ray dispersive microanalysis. The single limiting membrane of the substrate-induced microbody was stained by a modified Gomori reaction for the presence of alkaline phosphatase, thereby suggesting the participation of this enzymic activity in the events associated with microbody chemistry. PMID- 2213436 TI - Invasive fusariosis associated with an injury by a stingray barb. AB - A previously healthy adult male suffered a wound to the dorsal ulnar aspect of his right hand by a stingray barb while fishing off the East coast of Florida. Two weeks after the imbedded barb had been surgically removed, an erythematous lesion developed around the wound. Histopathologic and microbiological studies revealed infection caused by Fusarium solani. The patient was successfully treated with debridement and skin grafting in conjunction with ketoconazole therapy. PMID- 2213437 TI - Hendersonula toruloidea as an agent of mycotic foot infection in Gabon. AB - Pathogenic fungi were isolated from 149 of 210 Gabonese patients with clinical signs of tinea pedis. Hendersonula toruloidea was isolated from 51 patients (34.2%), either alone (in 25%) or in association with a dermatophyte species or Candida albicans. Clinical signs of H. toruloidea infection closely resembled those of dermatophyte infection except that hyperkeratinization of the soles was most often associated with infection by H. toruloidea. H. toruloidea mycelium could be readily distinguished from dermatophyte mycelium on direct examination of skin scrapings. All the H. toruloidea isolates closely resembled the Type 1 isolates described by Moore, both microscopically and macroscopically. The importance of establishing a mycological diagnosis of this infection and the therapeutic implications of infection with H. toruloidea are discussed. This fungus was isolated from 34% of our patients from Gabon with clinical tinea pedis. PMID- 2213439 TI - Isolation and characterization of a Paracoccidioides brasiliensis strain from a dogfood probably contaminated with soil in Uberlandia, Brazil. AB - We report the isolation of a strain of Paracoccidioides brasiliensis from a dogfood, probably contaminated with soil, in a Brazilian city. The fungus was isolated on appropriate culture media, and when inoculated into a guinea-pig testis produced orchitis with abundant fungal elements. Histopathology of sections of the testicle showed an inflammatory reaction with P. brasiliensis inside monocytes. Immunological identification confirmed the identity of the isolate. PMID- 2213438 TI - Candida albicans--do mycelia matter? AB - Growth of Candida albicans in the mycelial phase is neither necessary for initiation of infection in the kidney of the mouse, following intravenous inoculation, nor for the establishment of chronic renal colonization. However, mycelial formation would appear to be important in the establishment of pelvic lesions with their associated pathological changes. Two mycelia-less mutants, CA 2 and MM2002, in the early stages of infection tended to develop in the glomeruli of the mouse kidney cortex while the wild-type parent strains spread throughout the cortex and medulla, with only occasional involvement of glomeruli. The mutants appeared to stimulate a milder inflammatory response than the parent strains. In chronic infections with wild-type strains, tangled masses of mycelia filled the renal pelvis, but pyelonephritis and hydronephrosis did not depend on a persistent cortical infestation. Yeasts of the mutant strains persisted in the body of the kidney and stimulated a continuing neutrophil response. Systemic infections with wild-type strains were eliminated by treatment with low doses of an azole antifungal drug, ICI 195,739, or with amphotericin B, whereas systemic infections with the mutant strains were much reduced, but not eliminated, by relatively high doses of either of the two drugs. Unlike azole drugs, amphotericin B does not show differential activity against the two morphological forms of C. albicans. Because kidney infections with the mutant strains are relatively resistant to amphotericin B as well as the azole tested, we conclude that the impressive activity of azoles in vivo may not be explained entirely by their inhibition of mycelial growth. PMID- 2213441 TI - Ongoing study into the immunology of Hirschsprung's disease. PMID- 2213440 TI - Enzyme-linked immunosorbent assay (ELISA) for detection of antibodies against Pityrosporum orbiculare. AB - IgG antibodies to Pityrosporum orbiculare were detected by an enzyme-linked immunosorbent assay (ELISA) in sera from 10 healthy adults and five healthy 6 month-old children. The ELISA showed 17-80 times higher antibody levels in adults than were found by an indirect immunofluorescence technique (IIF) used in earlier studies. Low titres of antibody were detected in the children. PMID- 2213442 TI - Papers presented at the 38th annual meeting of the Surgical Section of the American Academy of Pediatrics. Chicago, Illinois, October 21-23, 1989. Part 2. Proceedings. PMID- 2213443 TI - The perioperative management of neonates with congenital oropharyngeal teratomas. AB - Oropharyngeal teratomas are rare congenital neoplasms that distort orofacial anatomy and often cause respiratory embarrassment at birth. Immediate management of such lesions should include establishment of a secure upper airway, radiographic exclusion of midline central nervous system anomalies, and early surgical excision to prevent asphyxia or permanent disfigurement. Perioperative assessment and surgical management are reported for three oropharyngeal teratomas. PMID- 2213444 TI - The effect of chloroquine and hyperthermia on murine neuroblastoma. AB - A number of reports suggest that hyperthermia is an effective adjunctive treatment modality in management of neural crest tumors. Recent studies have demonstrated a synergistic effect of induced hyperthermia when coupled with chloroquine in an in vitro model. This study examines the effect of chloroquine and hyperthermia in an in vivo murine neuroblastoma model. Forty-seven Ajax white mice (weighing 20 to 30 g) received a subaxillary tumor burden (C-1300 murine neuroblastoma) per trochar (1.25 x 10(6) cells). The tumor was then incubated for 9 days. Mice were then divided into four groups: group 1, controls (n = 15); group 2, hyperthermia (n = 12); group 3, chloroquine (n = 10); and group 4, chloroquine with hyperthermia (n = 10). Hyperthermia was induced with 40 to 69 mW/cm2 at 2,450 MHz microwave radiation for 4 minutes to achieve a temperature of 41.5 degrees C for 10 of 14 treatment days. Chloroquine was administered intraperitoneally at a dose of 40 mg/kg body weight for 10 of 14 treatment days. Mice were weighed and tumor size was determined daily. Animals were killed on day 21 and postmortem examination was performed, with tumors graded histologically. Animal weight, tumor weight, and tumor size were similar for all groups (P greater than .05). Mortality was 6% in group 1, 25% in group 2, 50% in group 3, and 40% in group 4 (P less than .05). Rate of tumor metastases was also statistically different from controls: group 1, 0%; group 2, 60%; group 3, 90%; and group 4, 90% (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213445 TI - Alcohol and the adolescent trauma population. AB - Trauma is the leading killer of children and adolescents between 1 and 21 years of age. Alcohol-impaired driving represents the single greatest cause of mortality and morbidity of children over the age of 6. We retrospectively reviewed 878 consecutive adolescent (age range, 16 to 20 years) trauma admissions for blood alcohol concentration (BAC). Four hundred sixty-seven patients had BAC drawn, 258 were BAC-negative (group I), 209 (48%) were BAC-positive (group II). The adolescent drinkers were then compared with a group of 748 adult drinkers (group III). Groups I and II differ in sex, age, time of day of the accident, Injury Severity Score, Glasgow Coma Score, and Revised Trauma Score, whereas group II and III differ by type of accident, type of injury, socioeconomic factors (bad debt), time of day of the injury, and BAC. There were no significant differences in TRISS predicted survival, actual survival, nor mean length of stay. We conclude that (1) alcohol is a significant contributor to injury during adolescence, and (2) adolescent drinkers differ from adult drinkers in their habits, demographics, and socioeconomic status. These socioeconomic differences have implications for the access to and cost-effectiveness of interventions. PMID- 2213446 TI - Transfusion requirements in conservative nonoperative management of blunt splenic and hepatic injuries during childhood. AB - Nonoperative management of splenic and hepatic injuries in children is safe, and the majority of those with isolated injuries do not require blood transfusion. Thirty-seven children were treated for blunt splenic or hepatic trauma from November 1983 to September 1989. There was one death in a patient with a lethal head injury. No operations were performed on those with isolated splenic or hepatic injuries. Three of those with multiple injuries underwent delayed laparotomy. Two had perirenal and retroperitoneal hematomas without active bleeding, and one had a bowel obstruction secondary to an intramural jejunal hematoma. There were no late complications related to the splenic or hepatic injuries. Eight children (22%) required surgery for other injuries. Twelve children were not transfused, including the majority (8/11) of those with isolated splenic or hepatic injury. The hematocrit of four of these children fell to below 28% and this anemia was well-tolerated. Two children with bleeding disorders (factor VIII [antihemophilic factor] and factor XII [Hageman factor] deficiency) did not require packed red blood cells transfusion. Two clinically distinct groups of children received blood transfusions: (1) eight patients with multiple injuries were transfused during initial resuscitation when unstable or during early operation for other system trauma (mean, 62.0 mL blood/kg body weight); and (2) three hemodynamically stable patients with isolated injuries and 14 stable patients with multiple injuries were transfused empirically after initial resuscitation solely because of decreasing blood counts. They received an average of 16.5 and 21.1 mL blood/kg body weight, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213447 TI - An analysis of pediatric trauma deaths in Indiana. AB - From June 1986 to May 1988, there were 1,931 childhood deaths recorded in Indiana. Eight hundred six children (0 to 18 years old) died as a result of trauma (41.4% of all deaths). Seventy percent of all traumatic deaths occurred in boys. Blunt trauma accounted for 54% of deaths, asphyxia or drowning 26%, penetrating trauma 15%, electrocution 3%, and burns 1%. Sixty percent of deaths occurred in rural areas and 40% occurred in urban centers; however, state-wide demographics define the population as 70% urban. The percentage of deaths due to trauma within a given race was: hispanic 71%, caucasian 42%, black 35%, and others 50%. However, when deaths occurring in infants less than 30 days of age were eliminated, the percentages changed: hispanics 70%, caucasian 45%, black 45%, and others 50%. Traumatic deaths were 1.6 times as likely to occur during the months of June through October (n = 85 deaths/mo) as opposed to November through May (n = 53 deaths/mo) (P less than .05). Mortality from burns was limited to children less than 5 years of age and penetrating trauma mortality was twice as likely to occur in children over 15 years (10% v 20%). Fifty-two percent of all traumatic deaths in children occurred between 15 and 18 years of age. Major burns account for only 1% of traumatic deaths in this state. Asphyxia and drowning were more common in young children, and blunt traumatic deaths more common in older children. In 1988, the first state-wide accident awareness program was instituted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213448 TI - Thoracic trauma in children: an indicator of increased mortality. AB - This study was undertaken to assess the significance of thoracic trauma as a marker of morbidity and mortality in children. During a 34-month period, 2,086 children younger than 15 years old were consecutively admitted to a Level I pediatric trauma center with blunt or penetrating trauma. For each child we prospectively recorded Trauma Score (TS), Injury Severity Score, (ISS), medical, and etiologic data. One hundred four children (4.4%) presented with thoracic trauma. The most common mechanisms of injury were pedestrian injury (36%), motor vehicle crashes (32%), and armed assault (12%). The most common injuries were pulmonary contusion (48%), pneumothorax, hemothorax, or pneumohemothorax (39%), and rib fractures (32%). Multisystem injury was present in 82% of the children. The mean TS and ISS were 11 and 27, respectively, significantly worse than scores for children without thoracic injury (15 and 7; P less than .0001). Seventy-one percent of the children were admitted to the intensive care unit, where they stayed an average of 6 days; 20% required surgery. The mortality rate was 26%. Injuries to the heart or great vessels had the highest mortality rate (75%), followed by hemothorax (53%), lung laceration (43%), and rib fracture (42%). Mortality for children with isolated chest injury was 5%, compared with rates of 20% for abdominal and chest trauma, 35% for head and chest trauma, and 39% for trauma to the head, chest, and abdomen. Less than 5% of the admissions to a pediatric trauma center incurred thoracic injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213449 TI - Delayed onset of intestinal obstruction in children after unrecognized seat belt injury. AB - The increased use of child safety seats and seat belt restraints has significantly reduced the incidence of severe head injuries associated with motor vehicular accidents. However, an increase in the number of both acutely recognized intestinal perforations and delayed obstructions due to ischemic strictures has been noted. This report describes two children with delayed onset of intestinal obstruction related to the "seat belt syndrome" who presented with bilious emesis 3 to 6 weeks following an unrecognized lap belt injury. At laparotomy, a volvulus around an omental band adherent to a resolving traumatic mesenteric hematoma was the basis of the obstruction in both cases. The volvulus resulted in a stricture in each instance that required resection and end-to-end anastomosis. The diagnosis of posttraumatic intestinal obstruction should be suspected in children who develop nausea and bilious emesis following motor vehicular accidents in which they were wearing lap belts. PMID- 2213450 TI - Diamond-shaped anastomosis for duodenal atresia: an experience with 44 patients over 15 years. AB - During the period between 1974 and 1988 44 patients were treated for congenital intrinsic duodenal obstruction using a diamond-shaped anastomosis (35 atresias, including two multiple atresias and nine stenoses). Neither gastrostomy nor transanastomotic tube was used. Postoperatively, oral feeding was started on days 2 to 6 (3.66 +/- 1.41 day). Intravenous fluid administration was discontinued on days 3 to 20 (7.54 +/- 3.58 day). Fourteen patients died, none related to the operative procedure. Of 30 survivors, 21 patients have been followed from 6 months to 15 years. Body weight was within the normal range at the latest visit. Current barium study performed in 19 patients showed no blind loop, megaduodenum, or anastomotic malfunction. The diamond-shaped anastomosis provides the following advantages: (1) early recovery of anastomotic function, and (2) avoidance of later complications, such as formation of a blind loop or anastomotic stenosis. PMID- 2213452 TI - Prevention of prolapse in pediatric enterostomas with purse string technique. PMID- 2213451 TI - Rectal duplications. AB - Recent experience with two cases of rectal duplication, which had been misdiagnosed as hemorrhoids, or fistula-in-ano with resultant delay in diagnosis, prompted us to review our prior experience with 11 of these unusual cases. Age at presentation ranged from newborn to 18 years (mean, 17 months). The most common presenting sign was a perianal or anal fistula, observed in five children. Two children presenting with fistulae had concomitant infection in the duplication. Other presenting signs included obstruction or prolapse caused by the rectal mass in three patients, rectal bleeding in three, and urinary retention in one. Some children presented with more than one finding. No associated spinal or vertebral anomalies were observed. Total excision was performed using a transanal approach in eight patients, postanal (transcoccygeal) in two, and posterior sagittal in one. Postoperative continence was normal in all patients. These cases illustrate that rectal duplications can be confused with other types of anorectal pathology including hemorrhoids, fistula-in-ano, and perirectal abscess. Total excision performed using a posterior sagittal, transanal, or transcoccygeal approach is curative. PMID- 2213454 TI - Operative treatment of anterior ectopic anus: the efficacy and influence of age on results. AB - In our experience, anterior ectopic anus (AEA) is a common cause of constipation in children. We have performed 54 anoplasties for AEA in the past 8 years. Seventy-eight percent of the patients were girls. The average age at surgery was 23.8 months and the average stool frequency prior to surgery was once every 3.2 days. Eighty percent of the children had undergone attempts at medical therapy. We compared the functional results of anoplasty in children by age. The children who had surgery prior to the age of 6 months had a significantly better outcome than did older children. These data suggest that patients with AEA have a better response to operative therapy when anoplasty is performed prior to 6 months of age. Early recognition, referral, and surgery is appropriate therapy in this patient group. PMID- 2213453 TI - Rectal prolapse: 17-year experience with the posterior repair and suspension. AB - Using a posterior repair and rectal suspension procedure for those patients who need surgical treatment of rectal prolapse, we have treated 46 patients over a period of 17 years at Children's Mercy Hospital in Kansas City, MO. One patient with caudal dysgenesis died of multiple congenital anomalies following two unsuccessful attempts at posterior repair and suspension. Four patients developed a recurrence afterwards, which was found to be due to sigmoid intussusception and, presumably, had played a major part in their original prolapse. Two of these required resection, one from the transanal approach and one from the transabdominal approach. One resolved spontaneously and another is as yet unresolved. Three patients had minor mucosal prolapse that was transient and two patients had extrusion of silk sutures but continued to have a very satisfactory result. Overall, 42 patients had satisfactory resolution of their rectal prolapse. Three of the four patients who had unsatisfactory results had associated anomalies that contributed to their poor outcome. PMID- 2213455 TI - Growing up "out-of-home". PMID- 2213456 TI - Physiologic sequelae of prematurity: the nurse practitioner's role. Part III. Congestive heart failure. AB - The premature infant with resultant respiratory disease may also have signs and symptoms of impending congestive heart failure that have a variety of causes. The nurse practitioner can be instrumental in the early identification and treatment of congestive heart failure. This article, the third in a series, provides a discussion of the pathophysiology, signs and symptoms, data collection, treatment modalities, and parental education that can assist parents when coping and dealing with congestive heart failure in their premature infant. PMID- 2213457 TI - Teaching children to resolve conflicts cooperatively. AB - Managing conflicts with and among children can be stressful and time-consuming for caregivers. Children and parents can learn to resolve differences in a cooperative way that allows each person to feel good about the process and the outcome. This article describes one cooperative conflict resolution process and suggests available resources. PMID- 2213458 TI - Childhood obesity: an update. AB - Childhood obesity is an increasing health problem in the United States, and it is positively correlated with eventual adult obesity. Childhood obesity is related to many of the same risk factors as adult obesity, most notably cardiovascular and psychosocial factors. Prevention or detection and management of the problem in childhood is warranted. This article describes assessment of obesity, predictors for its development, and components of treatment programs that are successful in children. Information is based on review of the literature and the author's experience working with obese children in a pediatric practice. PMID- 2213459 TI - Health services in child day-care centers: a survey. AB - This descriptive study examined the types of health services provided by 49 child day-care centers. A questionnaire was used to collect data from the day-care center directors. The study explored the existing health services and education and training for children, parents, and staff. The study also explored services that the centers would like to offer. Fewer than 50% of the day-care centers offered more than three primary care health services for children. The provision of health education and training for children, parents, and staff varied widely, but these services were offered more frequently than primary care health services. Directors were very interested in offering more comprehensive primary care services, options for sick-child care, and education and training in the areas of safety, disease prevention and management, child development, and availability of community resources. Directors cited infectious disease prevention and management, sick-child care options, and staff training as their most pressing health issues. Recommendations are made for improving the delivery of health services to day-care centers. PMID- 2213460 TI - Tools for assessing stress in children. PMID- 2213461 TI - Adolescent mothers. PMID- 2213462 TI - The role of the Physician Payment Review Commission in Medicare payment reform. AB - As an observer of the Physician Payment Review Commission, one is struck by the generous physician presence. As originally conceived, this make-up was perhaps appropriate. However, the policies inherent in the development of Medicare payment reform are changing the way many think regarding the value of health services and the manner of payment for such services. Nursing will be affected by these reforms. Cooperation, collaboration, consensus, and a strong united presence during the next year's deliberations by the Commission will serve the nursing profession well. PMID- 2213463 TI - Periodontal disease activity: a critical assessment. AB - Review of investigations using longitudinal probing and radiographic assessments indicate that the prevalence, magnitude, rate, and temporal patterns of periodontal destruction as well as the ability of clinical and laboratory tests to detect and predict loss of clinical attachment need further investigation. These unresolved issues are discussed and their impact on the practice of periodontics is examined. PMID- 2213464 TI - Effects of anesthetics containing epinephrine on catecholamine levels during periodontal surgery. AB - Nine stable cardiovascular disease patients were evaluated in a double-blind cross-over trial during periodontal surgery using 2% lidocaine with epinephrine 1:100,000 or lidocaine alone. In the lidocaine with epinephrine group, epinephrine levels increased from 198 +/- 54 pg/ml to 592 +/- 166 pg/ml at 2 minutes post-injection. In the lidocaine alone group, epinephrine levels increased from a baseline of 115 +/- 34 pg/ml to 150 +/- 34 pg/ml at 2 minutes post-injection. Despite these elevations in epinephrine, no significant changes in heart rate or mean arterial pressure were noted. Plain lidocaine provided unsatisfactory levels of hemostasis and/or anesthesia during periodontal surgery. This study documents acute elevations in plasma epinephrine levels following local dental anesthesia for periodontal surgery. These elevations in plasma epinephrine failed to produce a significant cardiovascular response in a group of stable cardiovascular disease patients. This suggests that the cardiac effects of local anesthetics containing epinephrine are small and that they can be safely used in stable cardiovascular disease patients. PMID- 2213465 TI - Periodontal repair in dogs: effect of saliva contamination of the root surface. AB - This study evaluated whether periodontal repair following reconstructive surgery may be compromised by saliva contamination of the root surfaces during the surgical procedure. Circumferential periodontal defects, 5 to 6 mm in vertical dimension, were surgically created in the mandibular premolars in 9 beagle dogs and immediately treated. The denuded root surfaces in left and right jaw quadrants in 4 dogs were treated with either filter sterilized saliva or saline, while in the remaining 5 dogs the root surfaces were treated with unfiltered saliva or saline. The wounds were closed and allowed to heal for 4 weeks. The dogs were sacrificed and tissue blocks prepared for histometric analysis. Results showed no difference between teeth treated with filtered or unfiltered saliva and the saline treated controls. Connective tissue repair to the root surfaces exceeded 70% of the defect height in all experimental groups. Regeneration of cementum and alveolar bone was limited and did not exceed 30% of the defect height. The results indicate that contamination of the root surface by saliva during the surgical procedure does not necessarily compromise connective tissue repair to the root surface. PMID- 2213466 TI - Formation of interdental soft tissue defects after surgical treatment of periodontitis. AB - This study monitored the development and repair of interdental soft tissue defects following surgical treatment of periodontitis in 21 patients. Open flap curettage was performed at 100 interdental areas with follow-up examinations 1, 3, and 6 months later. Interdental gingival contours were assessed both clinically and indirectly with silicone elastomer impressions from which stone models were obtained; defect depths were then calculated using the Reflex Microscope. Two types of defect were identified at the 1-month follow-up: 13 interdental clefts (mean depth, 1.8 mm); and 30 craters, (mean depth, 1.6 mm). Although clefts tended to persist, craters showed a strong tendency to repair. Thus, at the 6-month follow-up, the depths of clefts and craters were 1.3 mm and 0.7 mm respectively. The development of soft tissue defects did not appear to be related to the use of a periodontal dressing nor did the existence of an underlying bone defect appear to be of etiological importance. Pre-operative probing depths, however, were positively associated with the occurrence of soft tissue craters (P = 0.02). Pre-operatively, the overall mean probing depth and frequency of bleeding on probing were 5.3 mm and 100% respectively. At 6 months, these values were reduced to 2.0 mm and 22%. When clefts, craters, and interdental areas with no soft tissue defect were compared, no significant differences in probing depth reduction or frequency of bleeding were observed at any time point.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213467 TI - Diphenylhydantoin-induced gingival overgrowth in man: a clinico-pathological study. AB - In a cross-sectional, epidemiological study of diphenylhydantoin-induced gingival overgrowth (DGO) in 60 epileptic patients, gingival lesion severity was statistically compared with other clinical, laboratory, and histopathological findings. Evident DGO was observed in 50% of patients, and positive correlations were detected between overgrowth severity and oral debris, calculus accumulation, plaque score, gingival inflammation, and probing depth. However, no valid correlation was observed between lesion and patient age, mouth breathing, daily drug dose, plasma diphenylhydantoin level, or duration of drug intake. Also, there were no significant correlations between connective fiber richness and the intensity of epithelial hyperplasia and severity of gingival overgrowth. PMID- 2213468 TI - Recolonization of the subgingival microflora after scaling and root planing in human periodontitis. AB - The purpose of this study was to evaluate the recolonization patterns of the subgingival microflora of adult periodontitis patients after a single session of scaling and root planing. In each of eight patients, three clinically diseased sites were investigated microbiologically by darkfield microscopy and cultural analysis. After initial clinical and microbiological parameters were determined, each subject received a single session of scaling and root planing but no oral hygiene instructions. Clinical indices were measured and microbial parameters were reassessed 7, 21, and 60 days after treatment in a manner such that each of the test sites was sampled only once after treatment. Recolonization was evaluated by matching any single site with its own preoperative site. A significant improvement in probing depth was noted for up to 60 days after treatment, while the gingival index did not change markedly during the course of the study. The microbial composition of treated sites 7 days after scaling and root planing, as determined by both cultural and darkfield data, was similar to that of periodontally healthy sites. Differences between cultural and darkfield data became apparent at the 21 day sampling point. The darkfield data showed that the sites consisted of cocci with few spirochetes. Cultural data demonstrated that the majority of the cocci were anaerobic, namely Streptococcus intermedius, Veillonella parvula, and Peptostreptococcus micros. At 60 days, there was no significant variation in any of the parameters from pretreatment levels. The most prevalent anaerobic rods prior to and 60 days after therapy were Fusobacterium nucleatum, Bacteroides gingivalis, and B. intermedius.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213469 TI - The retrocuspid papilla of the mandibular lingual gingiva. AB - The retrocuspid papilla (RCP) is a circumscribed nodule that lies lingual to the mandibular cuspid on the gingival tissue. RCP is observed more frequently in young children and seems to regress or disappear with age. Little information is available in the literature on this entity and there are contradictory reports regarding its histologic features. Histomorphologic analysis of 30 specimens diagnosed as RCP revealed that in most cases (80%) it is composed of loosely arranged delicate fibrous connective tissue with stellate and multinucleated fibroblasts. Elongation of the rete ridges and/or increased vascularity are also present in a significant number of cases. Stellate and multinucleated fibroblasts are not unique to RCP and they have been described as prominent histologic features in other lesions of skin and mucous membrane. RCP is considered to be a "normal anatomical structure" or an "anatomic variation" of the gingiva. The clinical significance of RCP is that it may simulate pathological gingival conditions from which it must be differentiated. PMID- 2213471 TI - Letters from V: adolescent personality development in sociohistorical context. AB - Systematic content analysis of personal documents is used to assess the course of personality development in one adolescent female exposed to traumatic historical and personal events, as well as more normative life changes. Seventy-one letters written by a young girl to her former teacher over a 9-year period comprise the data for this study. Our analyses assess the normal developmental processes of preoccupation with identity formation and the establishment of intimate relationships, as well as responses to life changes (emigration, marriage, pregnancy). Overall, results suggest that despite serious challenges and losses, this individual experienced normal personality development throughout her trying adolescence. In addition, particular life events affected the course of that development. Factors which may have facilitated her resilience are discussed. PMID- 2213470 TI - Generalized juvenile periodontitis: report of a familial case followed for 5 years. AB - The case of a family, followed for 5 years and showing an exceptionally high prevalence of Generalized Juvenile Periodontitis (GJP), is presented. Two siblings were affected by a severe form of GJP meanwhile the dycorial twin of one was periodontally healthy. Both the affected siblings showed infection by Actinobacillus actinomycetemcomitans (Aa), but only one presented a reduced chemotaxis of the peripheral PMNs. The dycorial twin consistently displayed a freedom from Aa and a reduction in the peripheral PMNs chemotaxis. The extraction of the compromised teeth in the two affected siblings has been followed by colonization of new sites by Aa; only repeated administration of systemic tetracyclines seems to protect the subjects from colonization of other sites. These findings may contribute to the understanding of the etiology, pathogenesis, and therapy of juvenile periodontitis. PMID- 2213472 TI - Social interactions of obese and nonobese women. AB - The stigma associated with obesity is likely to limit the opportunities obese women have to develop social skills. This hypothesis was tested by having obese (n = 15) and nonobese (n = 22) women converse on the telephone with college students who were unaware of the women's weights. Ratings made by judges who listened to the women's contributions to the conversations but who were unaware of their weights showed that obesity was negatively related to judgments about the women's likability, social skills, and physical attractiveness. The telephone partners of obese women rated the women and themselves more negatively than did the partners of nonobese women. Obese and nonobese women generally did not differ in their evaluations of their own and their telephone partners' behavior, and they also did not differ on a measure of social self-esteem. These findings suggest that there are real differences in the social behavior of obese and nonobese women and that these differences affect the impressions formed by those with whom they interact. PMID- 2213473 TI - Distress and restraint as superordinate dimensions of self-reported adjustment: a typological perspective. AB - Individual differences in distress and restraint have recently been validated as two superordinate dimensions of social-emotional adjustment (Weinberger, 1989). In two samples (N1 = 139; N2 = 136) of university students, scores on these dimensions were jointly used to define six higher order personality styles: reactive, sensitized, oversocialized, undersocialized, self-assured, and repressive. To evaluate this typology, group differences were investigated on 28 measures within seven domains related to adjustment: self-expression, emotional control, proneness to personality disorders, physical illness, self-concept, neurotic symptoms, and impulse gratification. One-way multivariate analyses of variance revealed significant group differences within each domain. Univariate analyses revealed significant differences on 26 of the 28 measures and marginally significant differences on the remaining 2. A large number of nonadditive patterns consistent with a priori group descriptions corroborated the utility of a person-centered, typological approach. The data also provided an empirically derived, prototypic description of each adjustment style. PMID- 2213474 TI - Mothers' attributions to their young children: the verbal environment as a resource for children's self-concept acquisition. AB - There has been a century of theorizing that self-conceptions begin to develop early, heavily involve language, are important aspects of personality, and are much influenced by others' reactions. Nevertheless, no one has heretofore probed the empirical characteristics and antecedents of mothers' language that might be relevant to their 2 1/2-year-old children's acquisition of self-conceptions. In this research, such "maternal attributions" were located in video transcripts of 3 mother-child pairs, each interacting for 300 minutes (Study 1), and of 35 mother-child pairs, each interacting for 35 minutes (Study 2), all in a seminaturalistic setting. Study 2 replicated and extended results from Study 1 regarding (a) types of occasion for maternal attributions; and (b) the attributions' specificity/abstractness, vocabulary content, substantive referent, explicitness/implicitness, evaluative tone, and direction toward the whole child or an aspect of the child. Antecedent-consequent relationships were found between children's roles in occasioning attributions and the language specificity and evaluative tone of the attributions. Results are discussed in terms of the development of the self. PMID- 2213475 TI - What's wrong with the picture? PMID- 2213477 TI - Anxiety responses of 5- to 11-year-old children during and after hospitalization. AB - The purpose of this study was to examine the anxiety responses of 5- to 11-year old children (N = 52) during and after hospitalization from their perspective. Change in anxiety over time was examined, as was the relationship between children's anxiety and age, sex, length of hospitalization, previous admission, and parental anxiety. Children demonstrated a decrease in anxiety from admission to discharge, whereas anxiety remained fairly constant from discharge to posthospitalization. Younger children (5 to 7 years), boys, and children not previously admitted were more anxious and did not show a decrease in anxiety over time. Findings of this study have implications for practice and further research. PMID- 2213476 TI - Therapeutic play and the hospitalized child. AB - It has long been recognized that there are many and varied definitions of play. This article briefly reviews normative play theory, differentiating it from its counterpart, therapeutic play. Three forms of therapeutic play (emotional outlet play, instructional play, and physiologically enhancing play) are described and clinical examples are given. PMID- 2213478 TI - Parents' perceptions of their child's acute pain experience. AB - Painful procedures, experienced by many pediatric patients early in their admission, have been identified by parents in our clinical practice as a source of stress. The purpose of this study was to examine parents' perceptions and concerns about their child's acute pain experience. A convenience sample of 71 parents of 62 children was given a questionnaire that focused on the child's pain intensity, the behaviors that indicated the child was in pain, and the parents' preparation for and involvement in the child's pain experience. The majority of parents were asking for more information about and greater participation in procedures that caused their child pain. PMID- 2213479 TI - Don't be fooled by statistical significance. PMID- 2213480 TI - The world's worst human-caused disaster. PMID- 2213481 TI - Women and children first? PMID- 2213482 TI - Portable spirometry. PMID- 2213483 TI - Assessing individual differences in proneness to shame and guilt: development of the Self-Conscious Affect and Attribution Inventory. AB - Individual differences in proneness to shame and proneness to guilt are thought to play an important role in the development of both adaptive and maladaptive interpersonal and intrapersonal processes. But little empirical research has addressed these issues, largely because no reliable, valid measure has been available to researchers interested in differentiating proneness to shame from proneness to guilt. The Self-Conscious Affect and Attribution Inventory (SCAAI) was developed to assess characteristic affective, cognitive, and behavioral responses associated with shame and guilt among a young adult population. The SCAAI also includes indices of externalization of cause or blame, detachment/unconcern, pride in self, and pride in behavior. Data from 3 independent studies of college students and 1 study of noncollege adults provide support for the reliability of the main SCAAI subscales. Moreover, the pattern of relations among the SCAAI subscales and the relation of SCAAI subscales to 2 extant measures of shame and guilt support the validity of this new measure. The SCAAI appears to provide related but functionally distinct indices of proneness to shame and guilt in a way that these previous measures have not. PMID- 2213484 TI - Possible selves and delinquency. AB - The relationship between possible selves and delinquency is explored. In this study, 238 youths between the ages of 13-16 who varied in the degree of their delinquency were asked to describe their possible selves. Although many similarities were found among their hoped-for selves, the groups of youth differed markedly in the nature of their expected and feared selves. The balance between expected possible selves and feared possible selves was the particular focus. Balance is hypothesized to occur when expected possible selves are offset by countervailing feared selves in the same domain (e.g., expecting a job, but fearing being unemployed). It was found that the officially nondelinquent youths were quite likely to display balance between their expectations and fears, unlike the most delinquent youth. In contrast, a conventional measure of self-esteem that indicates how people feel about themselves currently did not predict degree of delinquency. PMID- 2213485 TI - Optimism, self-mastery, and symptoms of depression in women professionals. AB - The construct validity and predictive utility of dispositional optimism were examined in a sample of 192 women professionals. By using covariance structure modeling with latent variables, opotimism (Scheier & Carver, 1985) and self mastery (Pearlin & Schooler, 1978) were found to be empirically distinct, although substantially correlated, constructs. Furthermore, although optimism and self-mastery were significant and negatively correlated with symptoms of depression, only self-mastery was independently associated with symptom levels. In addition, no evidence was found that optimism and self-mastery interact to influence depressive symptoms. These results suggest that the apparent predictive power of optimism may derive from its substantial overlap with self-mastery. Implications for the assessment and interpretation of optimism and self-mastery are discussed. PMID- 2213487 TI - Social schemata of peripheral changes in emotion. AB - Psychophysiological research failed to establish consistent physiological patterns differentiating emotion. Recent data showed that people verbally report experiencing peripheral changes that differ among emotions. The present studies tested the hypothesis that these reports originate in social schemata. Study 1 showed that Ss' reports of peripheral changes experienced during actual emotion do not differ from those defined in social schemata. Studies 2 and 3 showed that these schemata are similar across cultures. Overall, these data suggest that (a) people can directly access schemata about peripheral changes in emotion, (b) people are likely to do so when they believe to be reporting actual memories of such changes, and (c) the specific patterns revealed by past research may reflect prototypical knowledge of emotion. Finally, the data highlight the various peripheral patterns as they exist in schematic knowledge of emotion. PMID- 2213486 TI - The fleeting gleam of praise: cognitive processes underlying behavioral reactions to self-relevant feedback. AB - We propose that a preference for favorable social feedback (i.e., self enhancement) requires only that feedback be characterized as favorable or unfavorable but that a preference for self-confirming feedback (i.e., self verification) is based on a more elaborate set of cognitive operations that requires both the characterization of feedback and a subsequent comparison of that feedback to a representation of self stored in memory. Study 1 set the stage for testing this hypothesis by showing that depriving people of processing resources interfered with their tendency to access their self-conceptions. In Studies 2 and 3, participants who were deprived of resources preferred the favorable, self-enhancing evaluator, whereas control participants displayed a preference for the self-verifying evaluator, even if that evaluator was relatively unfavorable. PMID- 2213488 TI - On-line and memory-based modification of attitudes: determinants of message recall-attitude change correspondence. AB - Experiments investigated the impact of message elaboration on attitude change message recall correspondence when attitude change occurs in an on-line (as attitude-relevant information is received), or memory-based (on the basis of retrieved attitude-relevant information) fashion. In 2 experiments, Ss' processing goals were manipulated to increase or inhibit on-line change and message elaboration. As predicted, Ss reported postexposure attitudes more rapidly in on-line vs memory-based conditions. Decreased message elaboration increased attitude-recall correspondence, regardless of when attitude change occurred. Increased elaboration produced elaboration-attitude judgment correspondence. Results suggest that recall of message content will best predict persuasion when message content is encoded free of elaborations, regardless of when attitude change occurs. PMID- 2213489 TI - Intimacy and liking: mutual influence and the role of unique relationships. AB - Traditional assumptions (e.g., there are traitlike differences in disclosure) predict that people who are generally liked should generally disclose (e.g., individual-level effects). In contrast, dynamic interactional models predict that significant disclosure-liking effects are apt to be a function of mutual influences in particular dyads (e.g., dyadic-level effects). To directly explore these issues and separately examine individual and dyadic effects, 45 sorority women were asked to indicate how much they disclosed to, received disclosure from, and liked each other. Social relations analysis (Kenny & LaVoie, 1984) revealed significant disclosure-liking effects only at the dyadic level, casting doubts on traditional assumptions and supporting a dynamic interaction model of disclosure-liking effects. Implications for personality and interpersonal relationships are discussed. PMID- 2213490 TI - What do women want? Facialmetric assessment of multiple motives in the perception of male facial physical attractiveness. AB - The multiple motive hypothesis of physical attractiveness suggests that women are attracted to men whose appearances elicit their nurturant feelings, who appear to possess sexual maturity and dominance characteristics, who seem sociable, approacheable, and of high social status. Those multiple motives may cause people to be attracted to individuals who display an optimal combination of neotenous, mature, and expressive facial features, plus desirable grooming attributes. Three quasi-experiments demonstrated that men who possessed the neotenous features of large eyes, the mature features of prominent cheekbones and a large chin, the expressive feature of a big smile, and high-status clothing were seen as more attractive than other men. Further supporting the multiple motive hypothesis, the 2nd and 3rd studies indicated that impressions of attractiveness had strong relations with selections of men to date and to marry but had a curvilinear relation with perceptions of a baby face vs. a mature face. PMID- 2213491 TI - Gender and social structure in the demand/withdraw pattern of marital conflict. AB - This study examined the effects of gender and social structure on the demand/withdraw pattern of marital conflict. In this pattern, the demander, usually the woman, pressures the other through emotional requests, criticism, and complaints, and the withdrawer, usually the man, retreats through defensiveness and passive inaction. In this study, 31 couples were assessed in 2 conflict situations: 1 in which husband wanted a change in wife and 1 in which wife wanted a change in husband. Data from husbands, wives, and observers consistently revealed a significant main effect of gender (wife-demand/husband-withdraw interaction was more likely than husband-demand/wife-withdraw interaction) and a significant interaction of gender and conflict structure (wife-demand/husband withdraw interaction was more likely than the reverse only when discussing a change the wife wanted). Separate analyses of demand and withdraw behaviors indicated that both husband and wife were more likely to be demanding when discussing a change they wanted and more likely to be withdrawing when discussing a change their partner wanted. However, men were overall more withdrawn than women, but women were not overall more demanding than men. PMID- 2213492 TI - Motivated recruitment of autobiographical memories. AB - We hypothesized that people motivated to believe that they possess a given trait search for autobiographical memories that reflect that trait, so as to justify their desired self-view. We led subjects to believe that either extraversion or introversion was desirable, and obtained convergent evidence from open-ended memory-listing tasks as well as from reaction-time tasks measuring the speed with which memories could be generated that this manipulation enhanced the accessibility of memories reflecting the desired trait. If people rely on their memories to construct desired self-concepts, motivated changes in self-concepts should be constrained by the content of available memories. Our final study demonstrates such constraints. PMID- 2213494 TI - Victim attributions and post-rape trauma. AB - This study assessed (a) the kinds of attributions victims make, (b) whether behavioral and characterological self-blame are associated with other variables as hypothesized (e.g., perception of future avoidability of being raped), and (c) whether behavioral self-blame is associated with better post-rape adjustment (Janoff-Bulman, 1979). Attributions and adjustment were assessed in a sample of adult female rape victims seen at a hospital-based rape crisis program. Many victims blamed themselves but tended to place more blame on external factors. The pattern of relations between behavioral and characterological self-blame and other attributional measures did not support the hypothesized distinctions between them. Both kinds of self-blame were significantly associated with increased post-rape depression (all ps less than .05). Attributions strongly predicted adjustment, accounting for up to 67% of the variance in 3-day post-rape depression. The theoretical and clinical implications of these findings are discussed. PMID- 2213493 TI - From the scene to the crime: the effect of alcohol and social context on moral judgment. AB - Forty men and women were given Kohlberg's Moral Judgment Interview (MJI) while drinking in a natural setting and were asked a series of questions about whether they should and would drive impaired. In a second testing in an academic context, these subjects were given an alternate form of the MJI and were asked whether they drove on the previous occasion. Forty additional men and women completed the MJI in an academic context and responded to the impaired driving questions hypothetically. Results revealed that Ss scored lower on moral maturity in the the social drinking contexts than in the academic contexts, especially when highly intoxicated. Ss responding hypothetically attributed more moral integrity to themselves than to others, indicating they would not drive impaired. The self righteousness of these attributions was apparent in the behavior of Ss who drove to the social drinking settings--all but 1 drove home, however impaired. PMID- 2213495 TI - Ego development and chronic illness in adolescents. AB - To examine the effects of chronic illness on the psychological growth process known as ego development, scores were compared on the Loevinger Sentence Completion Test for 36 teens (16 boys, 20 girls) with chronic illness and 50 teens (16 boys, 34 girls) without chronic illness. Their ages ranged from 13 to 21 years, with a mean of 17.4 years. Most were Black (37%) or Hispanic (41%) and lived in poor or working-class neighborhoods. When age, sex, and Peabody Picture Vocabulary Test (PPVT) scores were controlled in multiple regression analyses, no direct association between ego development stage and presence of chronic illness, severity of illness, age at onset, or duration of illness was found. Analysis of the chronically ill group alone revealed a significant PPVT X Severity interaction, indicating that ego development in chronically ill teens is lower when illness is more severe and verbal IQ is higher. PMID- 2213496 TI - Is the traditional role bad for women? AB - A sample of 112 women, tested first as college seniors in the late 1950s, were classified according to the traditionality of their life stories at age 43. This classification based on demographic criteria was supported by low to high scores on the socialization scale of the California Psychological Inventory (CPI). Traditionality of role at age 43 was related to CPI well-being and effective functioning at age 21. However, the traditional role was associated with several adverse changes in psychological and physical health by age 43. Both homemakers and women low in traditionality may have suffered from being less in synchrony with the social clock than they had been in college. Except for low energy, traditional women in the labor force (neo-traditionals) seemed to be role juggling with success. PMID- 2213497 TI - Social support and immune function among spouses of cancer patients. AB - This study investigated whether social support was related to immune function among spouses of cancer patients. Effects of depression and negative life events were examined as potential mediators. Results showed evidence of greater immunocompetence on 2 of 3 dynamic measures: natural killer cytotoxicity and proliferation response to phytohemagglutinin among spouses who reported high levels of social support. All six components of social support assessed by the Social Provisions Scale (Cutrona & Russell, 1987) were strongly related to these indices of immune function. No evidence was found for mediation by either life events or depression. PMID- 2213498 TI - Forming impressions from incongruent traits. AB - The factors that affect the ease with which impressions are formed from incongruent trait pairs are investigated. In Experiments 1 and 2, trait pairs that were both descriptively and evaluatively congruent, as well as ones that were only evaluatively congruent, were found to be more imaginable and to be perceived as more frequently co-occurring than incongruent trait pairs. In Experiment 3, response latency provided a converging measure of ease of imaginability. Experiment 4 examined written descriptions of targets described by these trait pairs, and found more attempts to integrate the congruent than the incongruent pairs. These findings are discussed in terms of the relation between laypersons' impressions of personality and formal personality assessment. PMID- 2213499 TI - Grief groups for children: a nurse's journey from personal pain to a national ministry. PMID- 2213500 TI - Spiritual care. Talking about faith with children. PMID- 2213501 TI - The San Francisco earthquake: finding a firm foundation when the earth cracks. PMID- 2213503 TI - Helping God's children grieve. PMID- 2213502 TI - Flip charts and fluorescent boots: health teaching in the Dominican Republic. PMID- 2213504 TI - "It's sad & you hurt a lot": letters from bereaved brothers & sisters. PMID- 2213505 TI - Immunologic and pathologic manifestations of the infection of rhesus monkeys with simian immunodeficiency virus of macaques. AB - The striking similarities between simian immunodeficiency virus (SIV)-induced disease in macaque monkeys and HIV-induced disease in humans make the SIV-induced macaque monkey an extraordinarily important model for the study of AIDS. The most significant difference between these lentivirus-induced syndromes is the more rapid progression of disease in SIV-infected monkeys. The immunologic and pathologic manifestations of SIV infections in rhesus monkeys are described. PMID- 2213506 TI - Interferon-alpha treatment leads to accumulation of virus particles on the surface of cells persistently infected with the human immunodeficiency virus type 1. AB - The effect of interferon-alpha (IFN-alpha) on virus replication in cells acutely infected with human immunodeficiency virus type 1 (HIV-1) and virus production from cells persistently infected with HIV-1 was studied. In both cell systems, significant suppression was observed. However, this suppression was not due to protein synthesis of the major viral proteins. Electron microscopy revealed the accumulation of intact virus particles on the cell surface of the cells treated with IFN-alpha. Thus, IFN-alpha might suppress the release stage of the particle from infected cells. PMID- 2213507 TI - A report of eight HIV-seropositive patients with major depression responding to fluoxetine. AB - This pilot study examined the effectiveness of fluoxetine in depressed human immunodeficiency virus (HIV)-seropositive asymptomatic patients. Eight patients, participating in an AZT trial who met criteria for major depression syndrome (DSM III-R), were treated with fluoxetine (20 or 40 mg/day) for 4 weeks. Initially, mean Hamilton Depression scores were 23.8 (range of 17-31), and improved to 6.4 (range of 3-10). All subjects maintained their remission over a 2-month follow up. Fluoxetine treatment may be effective in treating major depression in HIV seropositive asymptomatic patients. PMID- 2213508 TI - Relationship between AIDS latency period and AIDS survival time in homosexual and bisexual men. AB - We identified 277 homosexual and bisexual men diagnosed with acquired immune deficiency syndrome (AIDS) whose estimated human immunodeficiency virus (HIV) seroconversion dates, ranging from 1977-85, could be well approximated. These men were from a cohort of 6,705 homosexual and bisexual men originally recruited for studies of sexually transmitted hepatitis B in San Francisco in 1978-80. We compared the time from HIV seroconversion to the initial disease diagnostic of AIDS (AIDS latency period) with the time from first AIDS diagnosis to death (AIDS survival time) and found no significant overall correlation between latency period and survival time. Both Kaplan-Meier and Cox proportional hazard stepwise analyses found the initial AIDS diagnosis to be significantly associated with latency period, with individuals first diagnosed with Kaposi's sarcoma (KS) having a shorter latency but longer survival than those first diagnosed with Pneumocystis carinii pneumonia (PCP) or other AIDS diagnoses. Individuals with KS tended to be diagnosed earlier in the epidemic compared to those with PCP and other non-KS diagnoses. The AIDS survival time was significantly associated with the initial AIDS diagnosis but not with the estimated year of seroconversion, the year of first AIDS diagnosis, age at seroconversion, or racial/ethnic group. The information presented here on the relationship between the AIDS latency period and survival times suggests a model for the pathogenesis of HIV infection in which there is continual deterioration of the immune system. The wider use of antiviral and prophylactic therapies both preceding and following a diagnosis of AIDS may change this model as both latency and survival times are improved. PMID- 2213510 TI - The risk of development of HTLV-I-associated myelopathy/tropical spastic paraparesis among persons infected with HTLV-I. AB - Using data obtained in national surveys of human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) conducted in Japan in 1987 and 1988, we estimated the yearly and lifetime risk that HAM/TSP will develop in an HTLV-I-infected person. "Definite" HAM/TSP was defined as slowly progressive myelopathy with antibodies to HTLV-I in both serum and cerebrospinal fluid. Estimates of HTLV-I infection rates in eight endemic prefectures, by age group and sex, were obtained from serologic studies of blood donors; population figures, by age group, sex, and prefecture, were obtained from the census. Of 589 definite cases of HAM/TSP reported nationally, 397 occurred in residents of the eight endemic prefectures; of these, 170 reported onset of illness during the years 1982-1988 (average incidence, 24.3 cases/year). Using the estimated HTLV-I infection rates and the 1985 census figures, we estimated the number of HTLV-I-infected persons in the eight prefectures in 1985 at 794,800. We therefore estimated the incidence of HAM/TSP among HTLV-I-infected persons at 3.1 x 10(-5) cases/year; assuming a lifetime of 75 years, the lifetime incidence is approximately one quarter of 1%. This estimate is important in counseling persons such as blood donors found to be infected with HTLV-I. PMID- 2213509 TI - Monte Carlo simulation of HIV infection in an intravenous drug user community. AB - Intravenous drug users are crucial to the understanding and control of human immunodeficiency virus (HIV) transmission. We have developed a population-based simulation of a community of intravenous drug users. This model was implemented using Monte Carlo techniques, which permit great flexibility in creating realistic social structures, to describe the needle-sharing network of drug users. We present the baseline behavior of this model in a generic community and demonstrate the model's utility for assessing public health interventions. Our early results demonstrate the powerful effects of social networks on HIV transmission and the importance of prevalence levels in assessing the effectiveness of interventions in the drug-injecting community. PMID- 2213511 TI - A study of HTLV-I and its associated risk factors in Trinidad and Tobago. AB - Seroprevalence of human T-lymphotropic virus type 1 (HTLV-I) among a sample of persons selected from a government register of businesses in Trinidad was 3.2% in 1,025 persons of African descent compared to 0.2% among 487 persons of Asian descent and 0% among 46 persons of European-descent. In Tobago, from a coastal village, among persons of African ancestry ascertained as part of a cardiovascular survey, the rate was 11.4%, which was significantly higher when corrected for age and race than the rate in Trinidad. The seroprevalence rate of antibodies to hepatitis A and B was also significantly elevated in Tobago compared to Trinidad. HTLV-I seroprevalence rates were higher in females than males while hepatitis A and B rates were not significantly different in the two sexes. For males, age was a significant determinant of HTLV-I seropositivity, while for females, age, markers of poor sanitation, and hepatitis B were each independently linked to HTLV-I seropositivity. The frequent occurrence of multiple infectious exposures in persons of lower socioeconomic circumstances in this tropical environment may result in immune activation that heightens susceptibility to HTLV-I infection. PMID- 2213512 TI - Prevalence of HIV infection among patients with leprosy in African countries and Yemen. AB - Screening for human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2) antibodies was carried out in the serum of 1,245 leprous patients and 5,731 controls selected in nine different centers from the Congo, Ivory Coast, Senegal, and Yemen Arab Republic. In Yemen, all sera were negative. In the Congo, the seropositivity among patients and controls was, respectively, 3.8 and 5.2%; in Senegal, it was 1.3 and 0.6%; and in the Ivory Coast 4.8 and 3.9%. Differences were not statistically significant, even considering lepromatous or tuberculoid forms (3.6% and 3.7%, respectively). HIV-2 antibodies were only detected in subjects from the Ivory Coast and Senegal. Using appropriate criteria for seropositivity (confirmation by Western blot, reactivity to HIV envelope glycoproteins) and a large selection of patients (several countries with several centers), it appears that leprosy (and specially the lepromatous form) is not a factor for HIV infection. PMID- 2213513 TI - Epidemiology of toxoplasma encephalitis and need for primary prophylaxis among AIDS patients in northern Italy. PMID- 2213515 TI - Prevalence of HIV infection in the Comoros Islands (Indian Ocean) PMID- 2213514 TI - Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with AIDS-related tumors and chemotherapy-induced bone-marrow suppression. PMID- 2213516 TI - The prevalence of oral ailments that are common in HIV infection in a Nigerian dental practice. PMID- 2213517 TI - Facilitating the interface between families and community systems: nursing roles in the ecological environment. PMID- 2213518 TI - Challenges and choices in child and adolescent mental health-psychiatric nursing. AB - Challenges to the profession of child and adolescent mental health-psychiatric nursing, and choices available to address these challenges, are examined. The challenges stem from the large numbers of children in need of mental health services, the many risk factors to which children and families are exposed, and society's inadequate responses. Research evidence demonstrates that the gap between mental health needs and services for children results not from ignorance, but rather from a lack of commitment to providing a coordinated system of mental health services. Nurses are among the most appropriate professionals to address these needs for a coordinated system of care, but are not viewed as child mental health experts by the public or by policymakers. Nurses can demonstrate that child mental health nursing programs are effective by choosing to support programs that work, by conducting research projects that test nursing interventions, and by educating students to meet the needs of children and families for coordinated and cost-effective care. Finally, nurses must publicize their successes so that the public recognizes nursing's role in promoting children's mental health. PMID- 2213519 TI - Barriers to disclosure among sexually abused male children. Implications for nursing practice. AB - This article identifies, through a critical review of current research, several factors that may account for the reluctance of male children to disclose details of sexual abuse. The factors then are related to implications for practice and research that are relevant for child and adolescent mental health nurses. PMID- 2213520 TI - A community-based program for emotionally disturbed children and youth. AB - The children and youth program is a multidisciplinary multi-agency project to train professionals to provide community-based services for emotionally disturbed children. A coordinating committee provides the central structure to process referrals and establish treatment teams. Nursing has played a significant role in developing this project and in providing services such as crisis intervention, in home family therapy/family education, and team collaboration/case management. PMID- 2213521 TI - Autonomic and cardiovascular responses of preschool children to television programs. AB - This exploratory study examined the heart rates (HR) and skin temperatures (ST) of 18 preschool children while they viewed two clips of everyday children's television (TV) programming. The measurements were made in a day care setting, in a naturalistic environment designed to mimic the real world of children's TV viewing. The purpose of the study was to determine whether cardiovascular and autonomic arousal to TV programming might occur in some children. Since a large body of psychosocial literature addresses the affects of TV violence on children, HR and ST were examined during exposure to scenes from Mr. Roger's Neighborhood and G.I. Joe cartoons. The Mr. Roger's clip was slow, rhythmic, prosocial, and nonviolent, while the G.I. Joe clip was fast-paced, staccato, colorful, and full of verbal and action violence. The study found a significant effect of exposure to the cartoon violence on HR, with HR increasing. ST decreased, but not significantly, and there was a significant effect of time on the ST, due possibly to habituation. This finding has relevance to nursing assessment, intervention, and education of parents and children, since TV viewing is a pervasive cultural phenomenon. The possibility of excessive or inappropriate autonomic and cardiovascular responsiveness in some children to TV must be considered. PMID- 2213522 TI - A proposed model of relapse prevention for adolescents who abuse alcohol. AB - Adolescents who abuse alcohol are being admitted to treatment centers in increasing numbers. However, relapse prevention, a critical aspect of recovery, rarely is addressed in this high-risk population. This article briefly reviews adolescent development, the current literature on adolescent drinking patterns and relapse, and analyzes current models of relapse prevention in adults. This information is then used to propose a relapse prevention model for adolescents. PMID- 2213524 TI - [Metabolic activation of carcinogenic N-nitrosodialkylamines]. AB - Chemical and biological properties of metabolically activated species of carcinogenic N-nitrosodialkylamines are reviewed. alpha-Hydroxy nitrosamines and their derivatives; alpha-acetoxy nitrosamines, alpha-hydroperoxy nitrosamines, alpha-phosphonooxy nitrosamines and alkanediazotates are included. Metabolic deactivation through denitrosation and metabolic activation through beta oxidation are also mentioned. PMID- 2213523 TI - Caring for the caretakers in times of disaster. The Hurricane Hugo experience. PMID- 2213525 TI - [Pharmacognostical studies on the folk medicine in Sichuan Prov. in China. II. On tu-er-feng derived from Gerbera plants]. AB - Tu-er-feng is one of famous Chinese folk medicines in Sichuan prov. for common cold with cough, rheumatism, etc. Its sources are said to be either whole plants of some Gerbera or Ainsliaea species of family Compositae. In the recent markets, two types of Tu-er-feng are surely available. In this paper, Tu-er-feng derived from Gerbera species are studied to clarify the botanical origin; comparing mainly with the internal morphologies of the leaves and roots of G. piloselloides, G. delavayi, G. nivea, G. anandria (= Leibnitzia anandria) and G. jamesonii. As the result, G. piloselloides is determined as the botanical origin of Tu-er-feng obtained from the recent 16 markets. PMID- 2213526 TI - [Pharmacognostical studies on the folk medicine in Sichuan Prov. in China. III. On tu-er-feng derived from Ainsliaea plants]. AB - In the previous paper, Tu-er-feng, one of Chinese folk medicines used locally in Sichuan prov., derived from the whole plants of Gerbera piloselloides of family Compositae, was pharmacognostically reported. In the recent markets, besides this known material, Tu-er-feng made of different components are found. In this paper, the Ainsliaea derivatives are studied to clarify the botanical origins; comparing anatomically with leaves and petioles of thirteen Ainsliaea species growing wildly in Sichuan prov. The result shows that A. glabra and A. rubrinervis are the ingredients. PMID- 2213527 TI - [Suppression of lipid peroxidation by sho-saiko-to and its components in rat liver subcellular membranes]. AB - In order to elucidate anti-inflammatory action of Sho-saiko-to, its components were analyzed and purified by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC), and their effects on lipid peroxidation were compared with those of Sho-saiko-to in guinea pig neutrophils, rat liver mitochondria and microsomes. The results obtained were as follows: 1) Sho-saiko to gave no effect on arachidonate- and PMA (phorbol 13-myristate 12-acetate) induced NADPH-O2- generation in neutrophils though it gave a weak LPS-like effect on the cells. No inhibition of reduced nicotinamido adenine dinucleotide phosphate (NADPH) oxidation was shown in liver microsomes. However, it markedly inhibited iron-induced lipid peroxidation in microsomes and mitochondria. 2) The active components to suppress lipid peroxidation could be concentrated in a lipid soluble fraction from the Sho-saiko-to solution. The ED50 values to give 50% inhibition of the mitochondrial lipid peroxidation were 160 ng/mg prot, and 50 micrograms/mg prot, for the lipid-soluble fraction and Sho-saiko-to, respectively. 3) The components in the lipid-soluble fraction were further separated by TLC and HPLC, and their inhibitory effects on the lipid peroxidation were examined. The active components were baicalein, ginsenoside Rf and baicalin, of which ED50 values were 0.2, 0.2 and 1 nmol/mg prot, respectively. Glycyrrhizin and its derivatives, ginsenoside (except ginsenoside Rf), and saikosaponins gave no effect in the concentration examined. 4) From these results anti-inflammatory action of Sho-saiko-to was discussed. PMID- 2213528 TI - [Studies on resistant mechanisms in the resistant bacteria to chlorhexidine. II. Chemical components of the cell membrane and the electron microscopical observation of cell surface structure of chlorhexidine-resistant bacteria]. AB - The mechanisms of resistance of Serratia marcescens and Pseudomonas cepacia to chlorhexidine were studied. Leakage of the cellular component such as protein was observed in a chlorhexidine sensitive strain (S1) of S. marcescens when S1 was treated with chlorhexidine at 40 micrograms/ml concentration, while this phenomenon was not observed in a resistant strain (R1). The following observations were made concerning about cell surface structure in the chlorhexidine sensitive and resistant strains of S. marcescens by chemical analyses of membrane components and electron microscopical studies of the thin sections of the cells. (1) When the S1 strains was treated with chlorhexidine, the outer membrane of the cells formed a wrinkled surface with irregular blebs, and some of which broke out to form various sizes of granules. The R1 strain did not undergo such morphological changes under the same conditions used in the sensitive strain. (2) A prominent protein with apparent molecular weight of 45 K was found exclusively in the R1 strain of S. marcescens as major outer membrane protein, while it was not found in S1 strain. (3) There were no differences in the composition of phospholipids and the amount of 3-hydroxytetradecanoic acid between S1 and R1 strains of S. marcescens. In Pseudomonas cepacia PCJ1 which is resistant to chlorhexidine, 50 K protein was also observed as a major protein of outer membrane of the cells. In contrast to the strain, a mutant of the strain, #102 which was obtained from PCJ1 strain by the treatment with methanesulfonic acid ethylester, did not possess the 50 K protein in its outer membrane. These data suggested that outer membrane components of bacteria were related importantly in resistant mechanism. PMID- 2213529 TI - [Morphine hydrochloride suppositories. I. Bioavailability of morphine hydrochloride suppositories in rats]. AB - Bioavailabilities of morphine after rectal administration of three different morphine-HCl suppositories (5 mg/kg) were evaluated in rats. The suppositories were prepared with three fatty bases (Witepsol H-15, Witepsol W-35, Suppocire AT) by the fusion method. The plasma and brain concentrations of morphine and its metabolites, morphine-3-glucuronide and morphine-6-glucuronide, were determined by high-performance liquid chromatography. The bioavailabilities of morphine after rectal administration were compared with those after intravenous and oral administration of morphine.HCl solution (5 mg/kg). The plasma levels of morphine after rectal administration of morphine.HCl solution were higher than those after oral administration, whereas the plasma levels of metabolite, morphine-3 glucuronide was lower than those after oral administration. Morphine after rectal administration of Witepsol H-15 suppository released more easily than other suppositories. The inter-animal variation in the plasma levels of morphine after rectal administration of Witepsol H-15 suppository was smaller than those of other suppositories. Results obtained in this study indicate that morphine.HCl suppository prepared with Witepsol H-15 is a promising material as preparation of suppositories. PMID- 2213531 TI - [Studies on the degradation of chitosan films by lysozyme and release of loaded chemicals]. AB - Chitosan films with or without chemicals of interest were prepared and degradation properties of chitosan films of themselves by lysozyme and releases of the loaded chemicals from the films were investigated. Enzymatic degradation rate of the films was dependent on the degree of deacetylation of chitosan used and decreased with an increase in its deacetylation. The acidic conditions accelerated the degradation compared to the neutral pH. Most of the water-soluble chemicals used in the present experiments except Coomassie Brilliant Blue with a strong acidic group and pullulan with a high molecular weight (5.8 x 10(4)-38.0 x 10(4], were rapidly released from the films within 1 h. The two chemicals described above were released only in the presence of lysozyme, and their release rates were controlled by the degradation rate of the films. PMID- 2213530 TI - [Morphine hydrochloride suppositories. II. Bioavailability of morphine hydrochloride suppositories in dogs]. AB - Bioavailabilities of morphine after rectal administration of three different morphine.HCl suppositories were evaluated in dogs, whose rectum was lavaged or non-lavaged. The suppositories were prepared with three fatty bases (Witepsol H 15, Witepsol W-35, Suppocire AT) by the fusion method. The release of morphine from the suppositories was examined after stored for two weeks at 30 degrees C. The plasma concentrations of morphine and its metabolites, morphine-3-glucuronide and morphine-6-glucuronide, were determined by high-performance liquid chromatography. The bioavailabilities of morphine after rectal administration were compared with those after intravenous and oral administration of morphine++.HCl solution. In the case of rectal lavaged dogs, the plasma levels of morphine after rectal administration of morphine.HCl solution were higher than those after oral administration of morphine.HCl solution. The release of morphine from Witepsol H-15 suppository was more rapid than those from other suppositories. Morphine after rectal administration of Witepsol H-15 suppository was rapidly absorbed in the rectum, and the inter-animal variation of its plasma levels was smaller than those of other suppositories. In rectal non-lavaged dogs, the bioavailabilities of morphine after rectal administration of morphine.HCl solution and suppositories decreased more than those of rectal lavaged dogs. Although the bioavailability of morphine after rectal administration of morphine.HCl was decreased by the influence of contents in the rectum, morphine from Witepsol H-15 suppository was more rapidly absorbed in the rectum, and the inter-animal variation of its plasma levels was smaller. These results indicate that, among their suppositories, Witepsol H-15 suppository is available for the terminal care of malignant disease. PMID- 2213532 TI - Spontaneous mutations in the galactose operons of Streptomyces coelicolor A3 (2) and Streptomyces lividans 66. AB - Mutations can be divided into two classes: point mutations (base changes, frame shifts) and DNA rearrangements (deletions, insertions, inversions etc.). In Escherichia coli K 12, DNA insertions account for up to 40% of spontaneous mutations that inactivate genes (for review, see CULLUM 1985) and the Insertion Sequences involved can also mediate deletions and inversions. We started to study spontaneous mutations in Streptomyces in the expectation of isolating transposable elements and chose the galactose genes as convenient system. When selection is made for resistance to the galactose analogue 2-deoxygalactose (2dgalR), gal K mutants are obtained that are defective in the enzyme galactokinase (Kendall et al. 1987). We isolated spontaneous 2dgalR mutations in the closely related strain S. coelicolor A 3 (2) and S. lividans 66 and cloned the gal K gene of the former strain. Adams et al. (1988) have cloned and sequenced the gal genes of S. lividans 66 and shown that they form an operon, the restriction map appears to be identical to that of S. coelicolor A 3 (2). In this paper we describe the characterisation of spontaneous 2 dgalR mutants in S. coelicolor A 3 (2) and S. lividans 66. PMID- 2213533 TI - Acremonium chrysogenum differentiation and biosynthesis of cephalosporin. AB - On the basis of structure-functional analysis of the development of Acremonium chrysogenum, e.g. under conditions either stimulating antibiotic synthesis or not conductive to production, a scheme was proposed representing the various ways in which morphological differentiation occurs in the culture in dependence on the directions of its metabolism. Three types of culture differentiation were determined. Type 1 differentiation is characterized by the transition of the vegetative stage into the reproductive one with the formation of conidia. Type 2 differentiation is characterized by the formation of typical arthrospores also being the reproductive form. Type 3 differentiation is characterized by the multistage transformation of the mycelium organization into the yeast-like one which is metabolically more active and is a producer of antibiotics and enzymes. In addition to the defined regularities in the development and differentiation of Acremonium chrysogenum structural peculiarities were observed which could be helpful to the search for regulators or specific enzymes taking part in the culture development. PMID- 2213534 TI - Autolytic reduction of the nucleic acid content in Candida utilis. AB - The nucleic acid content in Candida utilis was autolytically reduced only after previous lyophilization of yeast cells or pretreatment of the cells with ethyl acetate. These pretreatments provided a sufficient permeability of the cell membrane system and thus enabled a reduction of the nucleic acid content. While deep freezing of the cells (-35 degrees C) had no positive effect on the degradation of nucleic acids, lyophilization of yeast cells led to a 75% decrease of the nucleic acid content. Furthermore, a 55% reduction of the nucleic acid content was proceeded without a concomitant loss of proteins. Similar results were obtained by using ethyl acetate. PMID- 2213535 TI - Sporothrix schenckii--a freeze-fracture study. AB - Freeze-fracture electron microscopy of a pathogenic dimorphic fungus Sporothrix schenckii revealed planar views of cell structures corresponding to those described already on thin sections. In addition to the characteristic differences in cell wall thickness between conidia, yeast forms and filaments, variations in plasma membrane invaginations were found. In conidia the invaginations were short and abundant, while in yeast forms they were scarce and longer. The plasma membrane of the filaments was smooth without invaginations. No differences were found in the frequency of intramembrane particles among the three forms. In the region of the septal pore the particles were circularly arranged with a characteristic partitioning on the P and E fracture faces. PMID- 2213536 TI - [Role of antibodies in periodontal disease]. AB - Bacteria and their products play a key role in the etiology of periodontitis. They activate the host immunologic system which produces specific immunoglobulins (Ig). Mainly IgA, IgG and IgM are found in the oral environment, in the saliva IgA are present as secretory IgA. In case of periodontitis, the tissular destruction could be practically explained by spontaneous hypersensibility reactions which may contribute to deteriorate the periodontal tissues. Considering the complexity of the factors involved in periodontal inflammation (i.e. bacterial variety, difference of properties, patient's individuality, difference of analysis methods), the question of the exact role played by the antibodies still remains open. PMID- 2213537 TI - Association between HLA system and periodontal diseases. AB - HLA system plays an important role in the regulation of the immune response. Association between HLA genes and disease has been shown for several disorders, in particular auto-immune diseases. HLA system may also be associated with periodontal diseases. It has been suggested that HLA-A2 is related to resistance in juvenile periodontitis and A9 to susceptibility in juvenile periodontitis (JP) and rapidly progressive periodontitis (RPP). DR2, DR4 and DQw1 may also be susceptibility factors in JP and RPP. If implicated in periodontal diseases, HLA system may be associated with low or non-responsiveness to plaque bacterial antigens which could result in disease progression. PMID- 2213538 TI - [Cyclosporin A gingival hyperplasia. Current status and report of a case]. AB - Cyclosporine A selectively inhibits T cell function with minimal effect on humoral immunity. It is largely used with success in kidney transplants. A clinical case of gingival overgrowth secondary to cyclosporine therapy in a 11 year old male who received a kidney transplant is reported. Surgical excision of the excess tissue, light and electron microscopic study are accomplished. PMID- 2213539 TI - [Arachidonic acid derivatives in periodontitis]. AB - A myriad of mediators of inflammation are involved in the onset and progress of periodontal disease. The exact roles of some of them are understood nowadays. In this paper, the current knowledge on the products of the arachidonic acid cascade (i.e. prostaglandins and leukotrienes) is reviewed. The main interests of these mediators are in their potential in diagnosing the phases of activity of periodontitis and the therapeutic prospects that their inhibition open up. PMID- 2213540 TI - [Immunology and protidology: study of immunological phenomena in periodontology in relation to serum proteins]. AB - The host response to the bacterial challenge varies from patients to patient. This paper deals with the protein profiles of patients suffering from different periodontal diseases. It is suggested that these profiles may help in diagnosing the given disease. PMID- 2213541 TI - [Immune response during experimental periodontitis in mice]. AB - Four groups of mice, each of a different genotype, were orally inoculated with Actinomyces viscosus. The resulting periodontal bone loss was monitored and the isotype specific anti-A. viscosus serum humoral immune responses measured by ELISA. Maximum periodontal bone loss occurred in all genotypes with inoculation of 1.6 x 107 colony forming units of A. viscosus. IgG and IgM isotype levels increased with inoculation of 1.6 x 107 colony forming units of A. viscosus in three of the four groups, indicating that IgA may be important in producing periodontal bone loss. PMID- 2213542 TI - [Polynuclear neutrophils and periodontal diseases]. AB - Periodontal diseases are bacteria associated diseases. The host response to these bacteria is critical. Non specific defense mechanisms are mainly mediated by the polymorphonuclear neutrophil which out numbers the others crevicular leucocytes. This paper reviews the beneficial and possible detrimental aspect of the neutrophil functions. PMID- 2213543 TI - Decreased lactoferrin content in granulocytes from subjects with Actinobacillus actinomycetemcomitans associated periodontal diseases. AB - Fourteen subjects were examined for lactoferrin content in PMNs of venous blood. Eight of the subjects were diagnosed localized juvenile periodontitis (LJP) and four adult periodontitis (AP), all having subgingival occurrence of Actinobacillus actinomycetemcomitans (A.a.). Two subjects had healthy gingival conditions and no detectable A.a. Deficiency or low PMN lactoferrin amounts were found in six of the eight subjects with LJP and in two of the subjects with AP. The reduced lactoferrin content in the PMNs was suggested to be depending on a cytotoxic factor produced by A.a. adding to an intrinsic PMN defect. PMID- 2213544 TI - [Antigen presenting cells during periodontal disease]. AB - The macrophages have an important function in the presentation of the antigen to the T lymphocytes. This presentation mandatory for the activation of the T lymphocytes is described. The Langerhans cells also play a role in the antigen presentation. These cells especially in the oral mucosa have been studied during the last years. PMID- 2213546 TI - Differential effects of carbachol on cytosolic calcium levels in vascular endothelium and smooth muscle. AB - Effects of norepinephrine (NE), carbachol (CCh) and histamine (HIS) on vascular tone and the endothelial and smooth muscle cytosolic C++ levels ([Ca++]i) were examined in rat aorta. The fura-2-Ca++ fluorescence emitted from endothelial and smooth muscle cells was detected at the endothelial surface. In the aorta with endothelium, NE increased both [Ca++]i and muscle tension whereas CCh slightly relaxed the muscle and increased [Ca++]i. The CCh-stimulated [Ca++]i was partially inhibited by verapamil. Addition of CCh to the NE-stimulated aorta relaxed the muscle with additional increase in [Ca++]i and positive correlation was obtained between the increase in [Ca++]i and relaxation. In the aorta without endothelium, NE increased both [Ca++]i and tension although CCh was ineffective. When endothelium was removed only from a small area from where the fura-2-Ca++ fluorescence was detected, CCh relaxed the muscle without changing [Ca++]i. In this preparation, NE increased both [Ca++]i and muscle tension and sequential addition of CCh relaxed the muscle with a small decrease in [Ca++]i, suggesting that Ca++ sensitivity of contractile elements is decreased. In Ca+(+)-free solution, CCh induced a transient increase in [Ca++]i and a decrease in muscle tension only in the presence of endothelium. HIS showed similar effects as CCh. By contrast, sodium nitroprusside decreased [Ca++]i and relaxed the muscle in NE stimulated aorta with or without endothelium. These results suggest that CCh and HIS increase [Ca++]i in the endothelial cells which regulates the synthesis and/or release of endothelium-derived relaxing factor. Endothelium-derived relaxing factor may decrease [Ca++]i in the smooth muscle cells and also decrease Ca++ sensitivity of contractile elements resulting in vasodilatation. PMID- 2213545 TI - Effects of long-term administration of haloperidol on electrophysiologic properties of rat mesencephalic neurons. AB - Haloperidol (1.5-1.7 mg/kg/day) was administered to rats via their drinking water for periods of either 4 weeks or 13 to 14 months, after which the animals were withdrawn from the neuroleptic for 1 or 2 weeks, respectively. Rats given haloperidol for 13 to 14 months exhibited significantly more perioral dyskinesias than controls. Single-unit extracellular recordings were obtained from the substantia nigra and ventral tegmental area in subjects under urethane anesthesia. After 1 month and after 1 year of treatment, a significant decrease in the mean firing rate of substantia nigra pars reticulata neurons was found. Subtle changes in the response of pars reticulata neurons to striatal stimulation were seen after extended haloperidol intake. No consistent effects of haloperidol administration for 4 weeks or 13 to 14 months were found for either the number of spontaneously active dopamine neurons or their firing rates. Histopathologic assessment of tissue from dorsomedial, dorsolateral and ventrolateral sectors of the striatum revealed no significant effect of long-term haloperidol treatment on neuronal cell counts. The results are discussed with reference to neuroleptic induced tardive dyskinesias. PMID- 2213547 TI - Prothymocyte activity is reduced by perinatal 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure. AB - The mechanism by which exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces thymic atrophy and cell-mediated immune suppression in experimental animals is poorly understood. A previous study from our laboratory found that terminal deoxynucleotidyl transferase-synthesizing lymphocyte stem cell populations in fetal liver and neonatal bone marrow, but not thymus, were profoundly altered after perinatal TCDD exposure, implying that a defect in the prothymocyte population in liver and marrow may play a role in the etiology of thymic atrophy in TCDD-exposed animals. In this report, we present results of experiments designed to directly assess the prothymocyte compartment in mice exposed to TCDD perinatally by examining the ability of these stem cells to reconstitute an irradiated thymus. Maternal TCDD exposure (15 micrograms/kg) caused a significant impairment of both fetal liver and neonatal bone marrow prothymocyte activity. These alterations occurred at tissue concentrations less than 200 fg of TCDD per mg. TCDD treatment also resulted in a mild reduction in colony-forming unit-spleen in these organs and a decrease in colony-forming unit granulocyte-macrophage in fetal and neonatal liver, but not bone marrow. Overall, these data provide evidence that alterations to early stages of T-lymphopoiesis, at the level of the prothymocyte, may be involved in the development of TCDD induced thymic atrophy and cell-mediated immunosuppression. PMID- 2213548 TI - An analysis of the action of phorbol 12, 13-dibutyrate on mechanical activity in rat uterine smooth muscle. AB - The effects of phorbol 12, 13-dibutyrate (PDB) on mechanical activity in the pregnant rat uterus were investigated in isolated strips. In Ca(++)-containing solution, PDB (2.5 x 10(-8) to 10(-6) M) increased in a concentration-dependent manner the amplitude of the electrically induced contraction, but had no effect on the resting tension. PDB (10(-7) M) had a dual action, stimulatory then inhibitory, on contractions evoked by K(+)-rich (40 mM K+) solution or oxytocin. The inhibitory effect appeared more rapidly and the percentage of inhibition was increased for 10(-6) M PDB, which in addition abolished completely oxytocin induced contraction after 20 min of application. PDB also reduced the amplitude of transient contraction evoked by oxytocin in Ca(++)-free solution. In saponin skinned strips, 10(-7) M PDB increased the contraction induced by pCa ranging from 7 to 6, whereas 10(-6) M PDB reduced all Ca(++)-activated contractions from pCa = 7 to pCa = 5. PDB had no significant effect on the Ca(++)-uptake and the Ca(++)-release mechanisms of the intracellular Ca(++)-store. All of the effects of PDB were antagonized by the addition of 1-(5-isoquinolinesulfonyl)-2 methylpiperazine (2 x 10(-5) M). In addition, the inactive phorbol 13,20 diacetate (10(-8) to 10(-6) M) had no effect on the mechanical activity in uterus. These results suggest the existence of different sites of action of PDB in rat uterus, via the activation of protein kinase C: 1) contractile machinery; 2) potential-dependent Ca channels; and 3) phospholipase C. PMID- 2213549 TI - Renal secretion of 3'-azido-3'-deoxythymidine by the rat. AB - The renal excretion of 3'-azido-3'-deoxythymidine (AZT) was investigated in clearance experiments in anesthetized rats. AZT was filtered freely and subsequently secreted, reabsorption being of minor importance. Probenecid, the classical inhibitor organic anion secretion, decreased AZT secretion. AZT, on the other hand, decreased p-aminohippurate secretion. These observations demonstrate that AZT is secreted by the organic anion secretory mechanisms. Cimetidine, an organic cation, also decreased AZT secretion at a concentration which did not inhibit the secretion of the organic anion, p-aminohippurate. This suggests that AZT might also be transported by the mechanisms secreting organic cations. However, as AZT did not inhibit the secretion of the organic cation tetraethylammonium, it cannot be concluded that AZT is transported by the mechanisms secreting organic cations. PMID- 2213550 TI - In vivo labeling of 5-hydroxytryptamine uptake sites in mouse brain with [3H]-6 nitroquipazine. AB - 6-Nitroquipazine (DU 24565; 6-nitro 2-piperazinylquinoline) is a very potent 5 hydroxytryptamine (5-HT; serotonin) uptake inhibitor. It has been demonstrated very recently that [3H]-6-nitroquipazine is a suitable radioligand for studying 5 HT uptake sites. The present study evaluates [3H]6-nitroquipazine as a radioligand for in vivo labeling of 5-HT uptake sites in mouse brain. Very high uptake of radioactivity in the brain after i.v. administration of [3H]-6 nitroquipazine was shown. Regional distribution of the radioactivity in mouse brain 3 hr after injection of [3H]-6-nitroquipazine was in the order (highest to lowest) hypothalamus greater than midbrain greater than striatum greater than hippocampus greater than cerebral cortex greater than medulla oblongata greater than cerebellum. The regional distribution of in vivo [3H]-6-nitroquipazine binding in mouse brain was highly correlated with that in rat brain obtained from previous in vitro binding studies. Coadministration of carrier 6-nitroquipazine (5 mg/kg) significantly decreased the radioactivity in the hypothalamus, whereas that in the cerebellum and cerebral cortex was increased. Because the cerebellum has very low density of [3H]-6-nitroquipazine binding sites, the radioactivity in the cerebellum could, therefore, reflect the amount on nonspecific binding and free ligand. Kinetic studies showed highest in vivo specific binding 1 hr after injection of [3H]-6-nitroquipazine and slow clearance of specific binding. Specific binding in the hypothalamus was inhibited in a stereoselective manner by the stereoisomers of norzimelidine. Furthermore, specific binding in the hypothalamus was reduced by several 5-HT uptake inhibitors, in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213552 TI - The effect of sulindac on the abnormal cough reflex associated with dry cough. AB - In order to determine the possible role of prostaglandins in the abnormal cough reflex in patients with dry cough, the effects of a cyclooxygenase inhibitor on cough symptoms were examined. This was measured by a cough symptom score and by the cough reflex sensitivity to inhaled capsaicin in a double blind, randomized, cross-over study comparing the effects of placebo with sulindac, 200 mg daily for 1 week. We studied six hypertensive patients with angiotensin converting enzyme inhibitor-associated cough and six patients with an idiopathic, dry, unproductive cough, all of whom had an increase in the sensitivity of the cough reflex. There was no change in blood pressure control in the hypertensive patients during sulindac therapy. The patients with the angiotensin converting enzyme-associated cough had a significant reduction in the cough symptom score and also a significant increase in the dose of capsaicin causing two or more coughs (threshold sensitivity) and that causing five or more coughs (near maximum response) during sulindac therapy as compared to placebo. In those patients with idiopathic, dry, unproductive cough, sulindac did not alter the symptom of cough or the cough reflex response to capsaicin. These results suggest that prostaglandins may be involved in cough associated with angiotensin converting enzyme inhibitor therapy, but are less likely to be important in the pathogenesis of more common dry coughs of unknown cause. PMID- 2213551 TI - Role of the central nervous system in hemodynamic and sympathoadrenal responses to cocaine in rats. AB - These studies were undertaken to examine the contribution of central nervous system mechanisms to the cardiovascular and sympathoadrenal effects of cocaine. Changes in systolic and diastolic blood pressure, heart rate and plasma catecholamine concentrations were determined in response to cocaine injected i.a. or i.c.v. in conscious unrestrained rats. Systemically administered cocaine produced brisk, transient dose-related increases in systolic and diastolic pressure at doses of 0.05 to 5 mg/kg i.a. Plasma catecholamine concentrations increased in a dose-related manner, reaching peak levels at 5 to 10 min after i.a. cocaine injection. Only the higher doses of cocaine induced reflex vagal bradycardia that was blocked by atropine (0.4 mg/kg i.a.). Propranolol (1 mg/kg i.a.) prolonged the duration of cocaine-induced hypertension and bradycardia. Ganglionic blockade with chlorisondamine (7.5 mg/kg i.a.) antagonized completely the cardiovascular and sympathoadrenal effects of cocaine, indicating that intact ganglionic transmission is required for full expression of the autonomic responses. Antagonist drugs selective for the D-1 or D-2 dopamine receptors attenuated effects of cocaine on plasma catecholamine concentrations but not on cardiovascular parameters. Intracerebroventricular injection of cocaine (50-250 micrograms) increased systolic pressure and plasma catecholamine concentrations, providing direct evidence for an action of cocaine in the central nervous system. These results demonstrate that cocaine acts centrally to increase sympathetic outflow leading to hypertension and reflex bradycardia in conscious rats. PMID- 2213553 TI - Interactions of free and liposomal amphotericin B with renal proximal tubular cells in primary culture. AB - We studied in vitro the renal toxicity of amphotericin B (AMB) and liposomal AMB using primary cultures of rabbit proximal tubular cells grown to confluence in serum-free medium. Toxicity was assessed by changes 1) in the Na(+)-dependent uptakes of P1 and alpha-methylglucopyranoside (MGP), characteristic functions of proximal tubular cells; 2) K+ release into the supernatant, dependent upon membrane permeability; and 3) lactic dehydrogenase release as a marker for cellular death. Cells were exposed for 1 hr to AMB, alone or intercalated in small unilamellar vesicles prepared with one of the following phospholipids: dipalmitoylphosphatidyl choline, distearoylphosphatidyl choline or dimyristoylphosphatidyl choline. Although AMB concentrations of 20 microM or less did not increase lactic dehydrogenase release, P1 and MGP uptakes were significantly reduced (50% inhibition) by 2.5 and 5 microM AMB, respectively. AMB toxicity was dose-dependent, up to 20 microM. Analysis of P1 and MGP uptake kinetics, after treatment of the cells with 10 microM AMB, showed that inhibition occurred through a decrease in Vmax (66 and 57% inhibition for P1 and MGP, respectively) without affecting Km value. K+ release appeared for 2.5 microM AMB and increased with higher concentrations. Alteration of Na(+)-dependent uptakes by AMB, which parallels K+ release, may result from an alteration of the sodium gradient. Na(+)-dependent uptakes and K+ release were unaffected by liposomal AMB, even at the highest concentration tested (80 microM). The protective effect of liposomes was the same regardless of the phospholipid used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213554 TI - Endothelium-dependent contraction induced by platelet-derived substances in canine basilar arteries. AB - The supernatant obtained from platelet-suspension incubated with thrombin caused contractions in both intact and endothelium-removed canine basilar arteries. Cyproheptadine (5 x 10(-7) M), which reduced the serotonin-induced contraction to about 20%, attenuated the supernatant-induced contraction to 51% in intact arteries and to 24% in endothelium-removed arteries. In both absence and presence of cyproheptadine, the supernatant-induced contraction of intact arteries was significantly larger than that of endothelium-removed arteries. The cyproheptadine-resistant contraction by the supernatant of intact arteries was attenuated by aspirin, OKY-046 (a thromboxane A2 synthetase inhibitor) and ONO 3708 (a thromboxane A2 antagonist), whereas such contraction of endothelium removed arteries was not affected by these agents. The concentrations of serotonin, ATP and ADP in the supernatant used here were approximately 3, 67 and 44 micrograms/ml, respectively. The mixed solution of serotonin, ATP and ADP, at the same concentrations as the supernatant, also induced cyproheptadine resistant, endothelium-dependent contractions in intact arteries. The contraction induced by the mixed solution in intact arteries was also attenuated by aspirin, OKY-046 and ONO-3708. The present experiments indicate that the supernatant causes endothelium-dependent contraction in canine cerebral arteries and that platelet-derived ATP and ADP contribute to this contraction. PMID- 2213556 TI - Nonpeptide angiotensin II receptor antagonists. XI. Pharmacology of EXP3174: an active metabolite of DuP 753, an orally active antihypertensive agent. AB - This report describes the pharmacology of (2-n-butyl-4-chloro-1- [(2'-(1H tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole-5-carboxylic acid (EXP3174). EXP3174 is a major metabolite generated after the oral dosing of 2-n-butyl-4-chloro-5 hydroxymethyl-1-[(2'-(1H- tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole, potassium salt in rats. It displaced [3H]angiotensin II (AII) from its specific binding sites in rat adrenal cortical membranes with an IC50 of 3.7 x 10(-8) M. In the isolated rabbit aorta, EXP3174 caused nonparallel shifts to the right of the AII concentration-contractile response curves and reduced the maximal response by 30 to 40% with an apparent pA2 value of 10.09 and a KB value of 10(-10) M. At 10(-6) M, EXP3174 did not alter the contractile responses to norepinephrine and KCl. In the spinal pithed rat, EXP3174 at 0.03 to 0.3 mg/kg i.v. also inhibited the pressor responses to AII and angiotensin III noncompetitively and did not change the pressor responses to vasopressin and norepinephrine. When given i.v. and cumulatively to normotensive rats at 0.003 to 0.3 mg/kg, EXP3174 did not alter blood pressure but inhibited the pressor response to AII. In conscious renal artery-ligated rats, EXP3174 decreased blood pressure with an i.v. ED30 of 0.038 mg/kg and a p.o. ED30 of 0.66 mg/kg. These results demonstrate that EXP3174 is a selective and noncompetitive AII receptor antagonist and lacks agonistic effect. As EXP3174 is a potent antihypertensive agent, it may be responsible for part of the antihypertensive effect of DuP 753 in rats. PMID- 2213555 TI - Selective changes in sensitivity to cholinergic agonists and receptor changes elicited by continuous physostigmine infusion. AB - A reduction in nicotinic receptors has been observed in brains of patients with Alzheimer's disease, and physostigmine, an indirect acting cholinergic agonist, has been suggested as a treatment of this disease. However, the effects of physostigmine treatment have not been thoroughly characterized. The central and peripheral effects of physostigmine were evaluated in C57BL/6 mice using a battery of behavioral and physiological tests that included respiratory rate, Y maze crossing and rearing activities, heart rate and body temperature. With the exception of the heart rate test, which was blocked by a peripheral muscarinic antagonist, all responses to physostigmine measured in the test battery seem to be mediated centrally. Sensitivity to physostigmine and to nicotine and oxotremorine were examined as were nicotinic and muscarinic receptors after continuous infusion of physostigmine. Mice (C57BL/6) continuously infused with physostigmine (0.1 mg/kg/h) for 10 days developed marked tolerance to physostigmine and exhibited a slight decrease in sensitivity to nicotine; sensitivity to oxotremorine was largely unaltered. Chronic physostigmine treatment resulted in a 62% inhibition of AChE activity and elicited a significant increase in the amount of L-[3H] nicotine binding in midbrain, hippocampus, striatum and colliculi; alpha-[125I]bungarotoxin and [3H]quinuclidinyl benzilatl binding were not changed. Although physostigmine treatment might partially reverse the reduction of brain nicotinic receptors seen with Alzheimer's disease, it is questionable whether it would be effective for a prolonged period since the up-regulated nicotinic receptors may not have normal function. PMID- 2213557 TI - Use of monoclonal antibodies as probes for the structure and biological activity of botulinum neurotoxin. AB - Experiments were done to help clarify the structure-function relationships that govern the interaction between botulinum neurotoxin and the cholinergic neuromuscular junction. Work was done with type E toxin in three different states: 1) unactivated (post-translational product before proteolytic processing), 2) activated (proteolytically modified product) and 3) denatured. Four different monoclonal antibodies were studied (E3, E14, E17 and E32), three of which were capable of diminishing the potency of the toxin. All four antibodies had approximately equivalent affinity for the unactivated and the activated forms of the toxin. Monoclonals E17 and E32 had little ability to interact with denatured toxin, suggesting they recognized conformational epitopes; monoclonals E3 and E14 retained partial ability to bind to denatured toxin, suggesting they recognized both conformational and linear determinants. When phrenic nerve-hemidiaphragm preparations were exposed to toxin under conditions that allowed binding but retarded internalization, the toxin remained accessible to antibodies. However, when tissues were stimulated in an effort to promote endocytosis, the toxin disappeared from accessibility to antibodies. The data indicate that various antigenic domains remain exposed after binding and suggest that certain parts of the toxin molecule undergo little or no conformational change during binding. The data further indicate that the molecular domains recognized by E14, E17 and E32 are internalized simultaneously. PMID- 2213558 TI - Thromboxane A2-mimetics are potent microvascular permeability factors in the conjunctiva. AB - These studies demonstrate that the thromboxane (Tx) A2 mimetics U-46619, U-44069 and carbocyclic-TxA2 elicit a microvascular permeability response in the conjunctiva. U-46619 and U-44069 are among the most potent microvascular permeability factors described to date for the conjunctiva; their potency is exceeded only by that reported for leukotrienes D4 and E4. The conjunctival microvascular permeability response to U-46619 was inhibited by the TxA2 antagonists daltroban (BM 13505) and SQ 29548. Prostaglandin (PG) D2 also increased conjunctival microvascular permeability, but was less potent than U 46619 and far less susceptible to pretreatment with daltroban or SQ 29548. PGE2, PGF2 alpha and the prostacyclin analog carbocyclin did not increase conjunctival microvascular permeability. It appears that the conjunctiva exhibits a unique microvascular permeability response to TxA2-mimetics: this view is experimentally supported by the absence of a cutaneous microvascular permeability response to U 46619, U-44069 and carbocyclic-TxA2. PMID- 2213559 TI - Characterization of serotonergic receptors mediating contraction of ovine umbilical artery. AB - Responses to serotonergic agonists were studied in isolated umbilical arteries obtained from fetal lambs within 2 weeks of term. The order of potency of the agonists was determined to be 2,5-dimethoxy-4-methyl-amphetamine (DOM) greater than 5-hydroxytryptamine (5-HT) greater than alpha-methyl-5-HT greater than 1-(3 chlorophenyl) piperazine = m-trifluoromethyl-phenylpiperazine greater than 8 hydroxy-dipropylaminotetralin greater than 2-methyl-5-HT greater than 1-(2 methoxyphenyl) piperazine. Variations in the sensitivity and potency of the agonists results primarily from the variation in the affinity for the 5-HT2 receptor and less so in the efficacy, alpha-Methyl-5-HT was a full agonist compared to 5-HT. The others were partial agonists. The mean KA values for 5-HT and DOM were 4.71 +/- 0.62 x 10(-7) and 0.36 +/- 0.04 x 10(-7) M, respectively. Contractions to 5-HT and DOM were antagonized by ketanserin with pA2 values being 9.4 and 9.1, respectively, suggesting that they act on the same receptor and that their responses are mediated by 5-HT2 receptors. Contractile responses to 8 hydroxy-dipropylaminotetralin, 2-methyl-5-HT and the phenylpiperazines [m trifluoromethyl-phenylpiperazine and 1-(3-chlorophenyl) piperazine] were also blocked by ketanserin (10(-8) M), indicating that contractions produced by these agonists were mediated by 5-HT2 receptors. No antagonism by MDL 72222 (3-tropanyl 3,5-dichlorobenzoate) of responses to 5-HT indicates that 5-HT3 receptors are not present in this tissue. PMID- 2213560 TI - Platelet activating factor (PAF) and tumor necrosis factor-alpha (TNF alpha) interactions in endotoxemic shock: studies with BN 50739, a novel PAF antagonist. AB - BN 50739, a new PAF receptor antagonist, was tested in vitro and in vivo for its capacity to block PAF, endotoxin and recombinant human tumor necrosis factor alpha (rTNF)-mediated effects. In vitro, BN 50739 blocked PAF-induced platelet aggregation by 60 to 100% at 0.2-1 x 10(-7) M (P less than .002), respectively. In the conscious rat, pretreatment (30 min) with BN 50739 (n = 5-13) dose dependently attenuated PAF-induced hypotension (-5 +/- 5 vs. - 43 +/- 2 mm Hg, P less than .01) and shortened the recovery time of mean arterial pressure (22 +/- 13 vs. 325 +/- 46 sec, P less than .01). BN 50739 (10 mg/kg i.p., n = 5-11) prevented endotoxin (14.4 mg/kg) induced-hemoconcentration (54 +/- 1 vs. 46 +/- 1%, P less than .01) and reduced 24-hr mortality (100 vs. 60%, P less than .05). Only partial protection was conveyed by BN 50739 against the hypotensive response to endotoxin (115 +/- 3 vs. 91 +/- 4 mm Hg, P less than .03). Also, BN 50739 attenuated the lipopolysaccharide-induced elevation of plasma thromboxane B2 (21.2 +/- 0.8 vs. 46.7 +/- 11.8 pg/100 microliters, P less than .01) and tumor necrosis factor-alpha (7523 +/- 3983 vs. 26,430 +/- 3541 U/ml, P less than .05), whereas leukopenia and thrombocytopenia remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213561 TI - Stereoselective inhibition of amantadine accumulation by quinine and quinidine in rat renal proximal tubules and cortical slices. AB - The renal organic cation transport system was examined. The accumulation of a nonchiral cation, amantadine, by rat renal proximal tubules and cortical slices was investigated, together with the effects of two diastereoisomers, quinine and quinidine. The proximal tubules actively concentrated amantadine with a tissue/medium ratio of 96.3 +/- 1.7 (mean +/- S.E.M., n = 18). Apparent Km was 85 +/- 2 microM and Vmax was 8.0 +/- 0.2 nmol/mg of tubular protein per min. Amantadine accumulation was inhibited competitively by quinine and quinidine with Ki values of 32 +/- 3 and 84 +/- 11 microM, respectively (n = 4). Amantadine was also concentrated by renal cortical slices with tissue/medium ratio of 3.3 +/- 0.3 (n = 4). Apparent Km and Vmax were 94.0 +/- 5.2 microM and 1.27 +/- 0.08 nmol/mg of tubular protein per min, respectively (n = 10). Quinine and quinidine again inhibited amantadine accumulation competitively by the slices, with Ki values of 368 +/- 28 and 780 +/- 84 microM, respectively (n = 4). A similar affinity (Km) for amantadine was observed in both preparations. However, the lower Vmax value in the slice system may be due to additional amantadine transport sites with lower capacity, lesser luminal accumulation and/or limited substrate(s) penetration in the cortical slices. In either preparation, quinine and quinidine functioned as competitive inhibitors and stereoselectivity was observed for the (-)-isomer, quinine, over the (+)-isomer, quinidine. Additional transport sites, reduced luminal substrate accumulation and/or diffusional restraints in the slices are also feasible mechanisms in explaining the differences in Ki values between the two preparations, and their relative contributions await further investigation. PMID- 2213562 TI - Serotonin-induced acute desensitization of serotonin2 receptors in human platelets via a mechanism involving protein kinase C. AB - Serotonin (5-HT)-induced changes in the levels of intracellular Ca++ were analyzed in human platelets, using the Ca+(+)-sensitive dye 1-(2-(5' carboxyoxazol-2'-yl)-6-aminobenzofuran-5-oxy)-2-(2' -amino-5'- methylphenox) ethane-N,N,N',N'-tetraacetic acid, pentaacetoxymethyl ester, to investigate the regulation of 5-HT2 receptor function. Serotonin mobilized intracellular Ca++ in a dose-dependent fashion from basal level of 98 +/- 2.7 and up to 211 +/- 5.8 nM with an EC50 value for 5-HT of 0.2 microM. Ketanserin, a 5-HT2 antagonist, reversed the 5-HT (10 microM)-induced Ca++ increase in a dose-dependent manner with an IC50 value of 2 nM. An initial treatment with 10 microM 5-HT abolished the response to a second treatment with 100 microM 5-HT, suggesting that 5-HT evoked an acute desensitization of 5-HT2 receptors in human platelets. Mezerein and phorbol 12-myristate 13-acetate, activators of protein kinase C, inhibited 5 HT-stimulated inositol monophosphate accumulation with IC50 values of 3 and 10 nM, respectively. Furthermore, a protein kinase C inhibitor 1-(5 isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride prevented the protein kinase C activator-induced inhibition against 5-HT-mediated inositol monophosphate accumulation. Mezerein also inhibited 5-HT (10 microM)-mediated Ca++ release with an IC50 value of 3 nM. 1-(5-isoquinolinesulfonyl)-2 methylpiperazine dihydrochloride prevented the inhibition by mezerein of the 5-HT stimulated Ca++ increase. Moreover, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride by itself enhanced the Ca++ spike induced by 100 microM 5-HT, the plateau phase induced by 10 microM 5-HT and the second response to 5-HT. These findings suggest that 5-HT2 receptor activation mobilizes intracellular Ca++ in human platelets and that this receptor may be desensitized acutely by a protein kinase C mediated feedback system. PMID- 2213563 TI - Nifedipine enhances amoxicillin absorption kinetics and bioavailability in humans. AB - Intestinal absorption of aminopenicillins in vitro uses the dipeptide carrier system. Recent experiments have reported calcium ion to be a cellular mediator of the regulation of electrolyte transport through the enterocyte membrane, especially the Na/H exchange which is partly responsible for the proton gradient energizing the carrier system. In order to assess the in vivo relevance of these data, we studied, in healthy volunteers, the influence of nifedipine, a calcium channel blocking agent, on the intestinal uptake of amoxicillin, a commonly prescribed and well-absorbed aminopenicillin. Results obtained show that 1) intestinal absorption kinetics of amoxicillin follows a zero-order process, which further substantiates the existence of a saturable carrier-mediated process for this antibiotic in humans and 2) calcium channel blockade significantly enhances both absorption rate (by 70%) and bioavailability of amoxicillin (by 21.4%) without modifying its distribution or elimination. These findings might suggest that nifedipine could enhance amoxicillin intestinal uptake by stimulating its active transport. PMID- 2213564 TI - Voltage and current clamp studies of muscarinic and nicotinic excitation of the rat adrenal chromaffin cells. AB - Characteristics of the muscarinic and nicotinic excitation of chromaffin cells that had been freshly isolated from the rat adrenal medullae were analyzed using voltage and current clamp techniques. A dose-dependent increase in the extracellularly recorded firing of cells was observed when 10(-6) to 10(-4) M acetylcholine (ACh) were locally applied to the cells in the vicinity of the target cell being recorded using a microinflow method. During voltage clamp recording at the resting membrane potential, ACh induced two different sequential inward currents: a transient current with a rapid rising phase (fast response) and an apparent inward current with a slow rising phase (slow response). The membrane conductance increased during the ACh-induced fast response, and it subsequently decreased during the slow response. The amplitude of the fast response decreased when the holding potential was shifted to depolarized levels, whereas the amplitude of the slow response increased with depolarization. Nicotine produced fast depolarization and a transient inward current that was reduced by the membrane depolarization. In contrast, muscarine induced a slow depolarization and an apparent inward current that increased with depolarization. Muscarine also reduced the inward K+ current that had been induced by the application of a high K+ medium to the outside of the cell at the resting membrane potential. It is suggested that muscarinic excitation is triggered by the suppression of K+ channels that are open at potentials near the resting membrane potential. The present results indicate that ACh-induced excitation of adrenal chromaffin cells involves two separate mechanisms mediated by nicotinic and muscarinic receptors. PMID- 2213565 TI - A patch clamp study of muscarinic excitation of the rat adrenal chromaffin cells. AB - A patch clamp study was performed to determine the ionic mechanisms underlying the muscarinic excitation of rat adrenal chromaffin cells. Burst-like, single channel currents with brief openings were recorded during cell-attached or cell free patch recording when the pipette solution contained high K+ media (70-140 mM), and the currents were recorded at potentials near the resting membrane potential. The amplitude and frequency of channel openings were dependent on the membrane potential and the K+ concentration of the external medium. Moreover, the single-channel currents observed with high K+ outside the membrane during inside out recording were suppressed by the addition of a K+ channel blocker, tetraethylammonium, inside the membrane. These results suggest that the single K+ currents recorded in the present study had properties similar to those of the resting or muscarine-activated K+ currents in atrioventricular cells of the rabbit heart. During cell-attached patch recording with the high K+ medium in the recording pipette, muscarine at concentrations of 10(-5) to 10(-4) M dose dependently decreased the frequency of the channel openings but did not affect the current-voltage relationship or the time constants of open and close time histograms. These results indicate that muscarinic-induced suppression of K+ currents is caused by a decrease in the number of active K+ channels at the resting membrane potential. PMID- 2213566 TI - Effects of long-term coenzyme Q10 and captopril treatment on survival and functional capacity in rats with experimentally induced heart infarction. AB - The effects of coenzyme Q10 (CoQ) and captopril on functional capacity, hemodynamics and survival were studied in 154 rats that recovered after experimental myocardial infarction. Rats were randomized into four groups receiving either CoQ, captopril, a combination of the two drugs or 1 ml of tap water once daily for 12 weeks from the day of coronary artery ligation. CoQ as well as captopril and the combined treatment significantly improved exercise capacity as evaluated by lactate production during a standardized treadmill exercise test. No significant changes in heart rate or mean blood pressure were observed during the study in the captopril-treated group. CoQ treatment increased the maximum heart rate significantly, whereas no effect on mean blood pressure was observed. Both captopril and CoQ decreased pulmonary congestion. Furthermore, the data may suggest that captopril prevents right ventricular hypertrophy seen in placebo-treated rats with large infarcts. This was not observed after CoQ treatment. Captopril treatment improved 3-month probability of survival (93%) as compared with placebo (74%) (P less than .05). CoQ and the combined treatment tended to improve survival, but this was, however, not statistically significant. PMID- 2213567 TI - Characterization of the effect of two 4-methyl piperidine derivatives of hemicholinium-3, A-4 and A-5, on choline transport. AB - A-4 and A-5 are tertiary and N-methyl quaternary 4-methylpiperidine analogs of hemicholinium-3 (HC-3). Previous work in this laboratory has shown A-4 and A-5 to be inhibitors of the sodium-dependent, high affinity choline uptake system (SDHACU). Their effects on choline transport were characterized further using neuroblastoma 41A3 cells. These cells rapidly take up choline through two separate mechanisms: a SDHACU system and a sodium-independent, low affinity uptake system (SILACU). A-4, A-5 and HC-3 decreased 5 microM choline transport in a dose-dependent fashion. The compounds were unable to decrease choline transport at 250 microM choline suggesting that they are inactive with respect to SILACU. All three compounds significantly increased the Km but not the Vmax for the SDHACU system, suggesting a competitive mechanism of inhibition. Ki values ranged from 18 to 25 microM for A-4, 20 to 26 microM for A-5 and 68 to 75 microM for HC 3. Dose-response curves for inhibition of choline transport by A-5 and HC-3 were not changed by a 24-hr pre-exposure of the cells to each inhibitor. However, after a 24-hr pre-exposure to A-4, a significantly different dose-response curve was obtained compared to the dose-response curve for A-4 in untreated cells. After a 24-hr pre-exposure, a 4-hr recovery period was sufficient to remove the effect of each compound. These data suggest that A-4 and A-5, like HC-3, inhibit the SDHACU, competitively and reversibly. PMID- 2213568 TI - Aging alters verapamil elimination and dynamics: single dose and steady-state responses. AB - Verapamil elimination kinetics and pharmacodynamic effects were studied in 29 healthy individuals (23-81 years of age) after single i.v. doses (0.15-0.22 mg/kg) and during infusions to reach stable plasma verapamil concentrations of 28 +/- 11, 57 +/- 19 and 112 +/- 26 ng/ml (mean +/- S.D.). Aging prolonged verapamil elimination (P less than .008): elimination half-life of 218 +/- 91 min in young (ages 20-39), 280 +/- 78 min in middle-aged (40-59) and 288 +/- 73 min in elderly (greater than 60). After single verapamil doses. 1) heart rate increased with lesser increases in elderly subjects; 2) blood pressure decreased (P = .006) with greater decreases in elderly subjects; 3) spontaneous P-R intervals increased with lesser increases in elderly subjects but, 4) atrioventricular conduction times increased during transesophageal pacing without detectable age differences in responses. During steady-state infusions, 1) heart rate during sinus rhythm was unchanged but atrioventricular dissociation with junctional rhythms developed in elderly subjects (3/9); 2) blood pressure decreased with greater decreases in the elderly; 3) spontaneous P-R intervals increased with lesser increases in the elderly but no age differences in paced P-R interval changes were detected at equivalent verapamil concentrations; 4) heart rate variation (during sinus rhythm) decreased in an age-independent manner as measured by decreases in the S.D. of R-R intervals and decreased power spectral content with greatest changes seen in high frequency (respiratory) content; and 5) heart rate and blood pressure responses to cold pressor and handgrip testing were not attenuated by verapamil. In conclusion, aging prolongs verapamil elimination and alters dynamic responses to verapamil with greater sinus node depression and hypotensive effects in elderly vs. younger subjects. Although less spontaneous P-R interval prolongation was seen on ECG of the elderly vs. young, underlying atrioventricular conduction was prolonged by verapamil independent of age as shown by results when pacing was used to eliminate frequency-dependent effects caused by differing heart rate responses. PMID- 2213569 TI - Cardiovascular effects of microinjection of angiotensin II in the brainstem of renal hypertensive rats. AB - The cardiovascular effects of microinjection of angiotensin II (AII) into the area postrema (AP), nucleus of the solitary tract (NTS) and rostroventrolateral medulla were studied in urethane anesthetized sham-normotensive (NT) and two kidney, one-clip renal hypertensive rats. Microinjection of AII (2-2000 ng) in the AP of renal hypertensive rats elicited a dose-dependent decrease in blood pressure, heart rate and renal sympathetic nerve activity. Similar effects were observed in the NTS. In the NT rats, low doses of AII (2 and 20 ng), either in the AP or NTS, were also depressor. High doses of AII (200-2000 ng) were needed to observe a modest pressor effect in the NT animals. A decrease in heart rate and renal sympathetic activity was observed with the pressor effect. The AII antagonist, [Sar1,Val5,Ala8]-AII, into the NTS or AP increased blood pressure and heart rate and inhibited the cardiovascular effects of low doses of AII in both group of rats. In contrast, [Sar1,Val5,Ala8]AII did not affect the pressor action of high doses of AII in the NT group. While the microinjection of AII into the rostroventrolateral medulla did not produce any significant cardiovascular effect in the renal hypertensive group, it resulted in a modest pressor effect in the NT rats. These results indicate that acute activation of AII receptors in the AP or NTS does not contribute to the pressor effect of AII in renal hypertensive rats. PMID- 2213570 TI - Evidence that the P2x purinoceptor of the smooth muscle of the guinea pig vas deferens is an ATP4- receptor. AB - In solutions containing Mg2+ and Ca2+, ATP is in equilibrium between the tetrabasic form (ATP4-) and its bidentate coordination complexes, i.e., MgATP2- and CaATP2-. We sought evidence to determine whether contractions of the smooth muscle of the guinea pig vas deferens to ATP are in response to ATP4- or its bidentate complexes. Contractions to ATP were elicited in seven modified Krebs Henseleit solutions containing varied concentrations of free and total Mg2+ and Ca2+ to alter the concentration of ATP4- at given ATPtotal concentrations. As the concentration of Mg2+ increased the concentration of ATP required to stimulate contraction to an equivalent degree also increased. Regardless of the free or total Mg2+ and Ca2+ concentrations, response magnitude was generally correlated with [ATP4-]. This suggests that ATP4- is the agonist at the P2x purinoceptor of the guinea pig vas deferens. The potency of ATP4- is high; the threshold, occurring at approximately 1 nM ATP4-, is 1000-fold less than that for norepinephrine. The implications of ATP4- as agonist are discussed in relation to adenine nucleotide potency, metabolism and P2 purinoceptor classification. PMID- 2213571 TI - Disposition of radioiodinated benzylguanidines in perfused rabbit lung: pharmacokinetics and effect of an organo-gold complexed antineoplastic agent. AB - SK&F 104524 (bis-[1,2-bis(diphenylphosphino)-ethane]-gold(I)-lactate) ([Au(dppe)2]+) is a lipophilic phosphine-coordinated gold complex that has significant antineoplastic activity. However, this agent has significant hepato- and cardiotoxicity and preclinical preliminary experiments indicate potential pneumotoxic effects. Accordingly, we sought to evaluate the acute effects of [Au(dppe)2]+ on pulmonary removal of two radioiodinated benzylguanidines [metaiodobenzylguanidine (MIBG) and 3-iodo-4-amino-benzylguanidine (AIBG)]. Pulmonary removal of MIBG or AIBG was measured by application of indicator dilution techniques in rabbit lungs, perfused with Kreb's bicarbonate (3% albumin; 50 ml/min). A bolus containing either [125I]MIBG or--AIBG and [99mTc]sulfur colloid was injected into the pulmonary artery and effluent was diverted to an in-line nuclear detection system. In initial experiments we characterized some pharmacokinetic aspects of the disposition of these amines. Removal of MIBG [R(MIBG)] and R(AIBG) were 59 +/- 3% (n = 14) and 24 +/- 2% (n = 7), respectively. Addition of unlabeled norepinephrine, MIBG or AIBG (3-100 nmol) to the injection caused similar dose-dependent reductions in removal of either amine. Lowering the temperature (13 degrees C) or reducing the sodium concentration caused significant reductions in removal. After 15 min of perfusion with [Au(dppe)2]+ (50 micrograms/ml), perfusion pressure doubled and R(MIBG) and R(AIBG) were each decreased significantly. At 30 min, perfusion pressure returned to control values whereas there was still a 36 and 61% reduction in R(MIBG) and R(AIBG), respectively. These data confirm that removal of benzylguanidines involves a saturable, sodium- and temperature-dependent process similar to that responsible for the removal of norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213572 TI - Effects of phorbol 12,13-dibutyrate on the vascular tone and on norepinephrine- and potassium-induced contractions of cat cerebral arteries. AB - Phorbol 12,13-dibutyrate (PDB), an activator of protein kinase C (PKC), induced slow-developing sustained contractions in segments of cat middle cerebral arteries. PDB-induced responses were not affected by phentolamine (1 microM) and endothelium removal, and were reduced by 1-(5-isoquinoline sulfonyl)-2 methylpiperazine (25 microM) and staurosporine (10 nM), PKC inhibitors. Forskolin (25 microM) produced a rapid and marked vasodilation in segments contracted with PDB. The 4 alpha-phorbol 12,13-didecanoate, an inactive compound, induced slight vasodilation. Preincubation with nifedipine diminished the responses elicited by PDB at all concentrations used. Ca-free medium containing 3 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA), but not 1 mM, markedly reduced the phorbol-induced responses at concentrations up to 10 nM. Nifedipine (0.1 microM) and forskolin (25 microM) produced a rapid and marked relaxation of PDB (10 nM)-evoked contractions in segments incubated in a Ca-free solution (1 mM EGTA), but PBD responses in 3 mM EGTA were not affected by nifedipine. PDB (10 and 100 nM) practically did not modify K-induced contractions, but reduced vasoconstrictions elicited by different norepinephrine concentrations; this effect was phorbol concentration and preincubation time-dependent. These results indicate that: 1) PDB induced PKC activation and contraction mainly produced by Ca entry (essentially at low PDB concentrations) through dihydropyridine sensitive Ca channels; 2) the activated PKC has elevated sensitivity for Ca; 3) PKC may be involved in the alpha adrenoceptors desensitization, but did not play an important role in the norepinephrine-induced contraction in these arteries. PMID- 2213573 TI - Dysmorphogenesis elicited by microinjected acetaminophen analogs and metabolites in rat embryos cultured in vitro. AB - Direct additions of acetaminophen (APAP), 3,5-dimethylacetaminophen, 3 hydroxyacetaminophen or 3-methoxyacetaminophen to the medium of cultured embryos each produced an increased incidence of morphologically similar, abnormally open anterior neuropores. Approximate concentrations required to produce an equal incidence were 0.5 mM, 1.0 mM, 0.1 mM and 0.75 mM, respectively. In contrast, 2.6 dimethylacetaminophen and N-acetyl-p-benzoquinoneimine failed to produce elevated incidences of abnormal neurulation unaccompanied by marked growth retardation. However, with intra-amniotic microinjections, 3-hydroxyacetaminophen and N-acetyl p-benzoquinoneimine were roughly equipotent for eliciting abnormal neurulation, whereas 3-methoxyacetaminophen required greater than 30-fold higher concentrations. This suggests that N-acetyl-p-benzoquinoneimine does not readily transit the visceral yolk sac and would likely not be a major factor in APAP elicited neural tube abnormalities unless generated in target tissues. The differential effects produced by two dimethylated (2.6 and 3.5) APAP analogs further suggest that sulfhydryl oxidation is associated more closely than sulfhydryl conjugation with the neurulation defect. Intra-amniotic microinjections of large quantities (3500 ng) of 7-hydroxy-2-acetylaminofluorene (7-OH-AAF) or APAP failed to produce the specific neurulation defect. Microinjections of 7-OH-AAF into the exocoelomic cavity effected the characteristic abnormal neurulation. Conversion by conceptal homogenates of 7-OH AAF was roughly 7- to 8-fold more rapid than conversion of APAP to respective catechol metabolites, and specific activities in yolk sac tissues were greater than those in the embryo. Rates of conceptal conversion to the quinoneimine were approximately 2- to 3-fold lower than catechol generation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213574 TI - Relative potencies of agonists and differential sensitivity to N-ethylmaleimide on muscarinic autoreceptors and postsynaptic receptors in rat hippocampus. AB - Relative potencies of nine muscarinic agonists as activators of autoreceptors regulating [3H]acetylcholine release or of postsynaptic receptors, stimulating inositol monophosphate (IP1) formation were determined in rat hippocampal slices. The agonists could be divided into three groups: 1) full agonists at both sites included oxotremorine-M, carbachol and methacholine; 2) full agonists at autoreceptors and partial agonists at receptors coupled to IP1 formation included oxotremorine, arecoline, bethanechol and RS-86; 3) McN-A-343 was a partial agonist at both sites. Arecaidine propargyl ester was a full agonist at autoreceptors but produced a biphasic stimulation of IP1 formation. Comparison of the EC50 values showed that agonists of groups 1 and 3 were more potent at autoreceptors than at IP1-coupled receptors. Group 2 agonists displayed similar potencies at the two types of receptors. N-Ethylmaleimide (NEM) was more active in antagonizing autoreceptors than IP1-coupled receptors in rat hippocampus. Concentration-response curves to carbachol at autoreceptors were shifted to the right in the presence of 10 microM NEM; 30 microM NEM reduced the maximal response. At postsynaptic receptors, higher concentrations of NEM (100 and 120 microM) were required for inhibition of maximum stimulation of IP1 by carbachol. NEM at 160 and 300 microM abolished the stimulation of IP1 induced by carbachol. These observations provide additional evidence that muscarinic autoreceptors differ from the postsynaptic muscarinic receptors that modulate IP1 formation. The similar rank order of agonist potencies between hippocampal autoreceptors and cardiac muscarinic receptors supports the hypothesis that these autoreceptors are of the M2 (cardiac) subtype. PMID- 2213575 TI - Presynaptic nicotinic receptors involved in release of noradrenaline and ATP from the prostatic portion of the rat vas deferens. AB - A differential response to cholinomimetic agonists in epididymal and prostatic portions of rat vas deferens was characterized. The prostatic portion was less sensitive to acetylcholine and carbachol than the epididymal portion. The contraction induced by cholinomimetic agonists was inhibited in the epididymal portion by atropine (1.0-3.0 nM) and in the prostatic portion by hexamethonium (0.1 mM). The contractile response of the prostatic portion to exogenous acetylcholine was not inhibited by textrodotoxin (1.0 microM) but was attenuated by reserpine treatment (10 mg.kg-1 i.p. 24 h) and by prazosin or alpha, beta methylene ATP. A combination of an alpha-1-adrenoceptor antagonist (prazosin) and P2 purinoceptor desensitization with alpha, beta-methylene ATP abolished the contractile response of the prostatic portion. The contraction induced by repetitive field stimulation of the prostatic portion was attenuated by hexamethonium whereas the response to a single stimulus was not modified. The data suggest that cholinomimetic drugs activate both nicotinic receptors located in nerve terminals of the prostatic portion and muscarinic receptors located in the smooth muscle cells of the epididymal portion, and that stimulation of nicotinic receptors induces the release of noradrenaline and ATP. PMID- 2213576 TI - Capsaicin-sensitive afferents activate a sympathetic intestinointestinal inhibitory reflex in dogs. AB - 1. In urethane-anaesthetized dogs, an intra-arterial infusion of capsaicin (0.7 14 nmol min-1) into a separated jejunal segment inhibited a vagally evoked cholinergic contraction of the other non-infused segments. The mechanism of this reflex was investigated. 2. The inhibition by capsaicin was abolished after bilateral splanchnic nerve section or cervical spinal cord transection (C5 or C6), but was unaffected by bilateral vagotomy. Decerebration partially reduced the inhibition. 3. The inhibition by capsaicin was abolished by pre-treatment with phentolamine or yohimbine, but was unaffected by prazosin or propranolol. 4. Sympathetic efferent discharge of the mesenteric nerve increased with capsaicin application, during which time vagally evoked contractions were inhibited. 5. Single-unit discharges of the major splanchnic and mesenteric afferents increased with capsaicin infusion to the loop which was innervated by the units. 6. Together the results implied that capsaicin stimulated canine intestinal primary afferents, resulting in the sympathetic intestinointestinal inhibitory reflex supraspinally. The inhibition of vagally evoked contractions may be due to a presynaptic inhibition via alpha 2-adrenoceptors, which are activated by the reflex. PMID- 2213577 TI - Electrophysiology of single heart cells from the rabbit tricuspid valve. AB - 1. The electrophysiology of single myocytes isolated from the rabbit tricuspid valve was studied using the patch-clamp method (whole-cell configuration). Cell dispersion was achieved by collagenase treatment, using the Langendorff retrograde perfusion procedure. 2. After isolation, and while incubating in the recovery (Kraftbruhe) solution, cells had clear striations and were mostly spindle-shaped, or rod-like (less than 10%), with length varying from 35 microns to over 150 microns, and diameter from 3 to 10 microns. 3. Upon exposure to Tyrode solution, the calcium-tolerant cells were mostly rounded with smooth surfaces and well-defined borders. The mean diameter of these cells was 15 +/- 5 microns (S.D., n = 9). A smaller percentage (about 30%) retained the original elongated shape. 4. Patch pipette recordings showed the presence of spontaneous activity in about 30% of round cells, and less frequently in elongated cells. Maximum diastolic potentials (MDPs) in the round cells averaged -82 +/- 6 mV, with a take-off potential of -56 +/- 3 mV (n = 9), and an average maximum upstroke velocity (Vmax) value of 6.3 +/- 0.6 V/s (n = 4). In quiescent cells, the mean resting potential was 69 +/- 12 mV (n = 43). 5. Voltage clamp ramps revealed a steady-state I-V relation with a negative slope region. The mean input resistance value was 25 +/- 9 M omega (n = 16) for the elongated, and 883 +/- 481 M omega (n = 8) for the round cells. 6. Hyperpolarizing 5 s pulses (holding potential = -50 mV) occasionally revealed a slow, time-dependent inward current whose peak increased progressively as a function of clamp potential. The slowly activating current was sensitive to caesium 2 mM), indicating its similarity to the so-called 'pacemaker current' (iF). In alternate voltage- and current-clamp experiments, blocking of iF did not stop pacemaker activity, but there was up to a fourfold increase in pacemaker cycle length. 7. In some cells, 5 s hyperpolarizing steps from a holding potential of -40 or -50 mV produced large, inwardly directed and voltage-dependent current surges that decayed rapidly with time, similar to the inactivation described for the inward rectifier current, iK1. The current was very prominent at voltages more negative than -100 mV, and its decay process was best fitted by two time constants, one fast and one slow. For example, at -150 mV the time constants were 61 and 634 ms. The inward current was blocked by barium (1 mM).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213579 TI - Suppression of cold-induced thermogenesis in full-term pregnant rats. AB - 1. Thermoregulation against cold exposure was studied in rats during pregnancy and early lactation, and compared with that of virgin rats. 2. When exposed to 0 degrees C for 60 min, rats which were within 24-48 h of parturition (pre-1-day rats) and those within 24 h of parturition (pre-0-day rats) showed significantly larger falls of colonic temperature (Tco) than virgin rats. The temperature decrease was greatest in the pre-0-day rats, being 4.1 +/- 0.4 degrees C (mean +/ S.E.M.) at the end of cold exposure, compared with a decrease of 1.7 +/- 0.3 degrees C in the virgin rats. The tail skin temperature fell to 0 degrees C during cooling in all virgin rats and in pregnant rats at each gestational stage. 3. During cold exposure at 10 degrees C for 30 min, pre-0-day rats also showed significantly larger falls in Tco (1.8 +/- 0.6 degrees C) than virgin (0.4 +/- 0.2 degrees C), pre-1-week (0.8 +/- 0.3 degrees C), post-0-day (0.3 +/- 0.3 degrees C) or post-1-week rats (0.4 +/- 0.3 degrees C). Although body weights in pre-0-day rats were far larger than those in virgin rats, the increase in oxygen consumption per animal during cold exposure was 50% lower in pre-0-day rats (2.2 +/- 0.5 ml/min) than in virgin rats (5.3 +/- 0.3 ml/min). There was no difference in basal oxygen consumption per animal between the late pregnant and virgin rats. 4. Within 24 h after parturition, both the decrease of Tco and the increase of oxygen consumption during cold exposure returned to the values observed in virgin rats. 5. The present results demonstrate clearly that cold-induced thermogenesis is significantly suppressed in rats at a late stage of pregnancy. PMID- 2213580 TI - Corticospinal volleys evoked by anodal and cathodal stimulation of the human motor cortex. AB - 1. In fifteen neurologically normal subjects, corticospinal volleys evoked by transcranial stimulation of the motor cortex were recorded from the spinal cord using epidural electrodes in the high-thoracic and low-thoracic regions during surgery to correct scoliosis. 2. Anodal stimulation at the vertex produced complex corticospinal volleys that could be recorded at both sites, with multiple waves analogous to the D and I waves documented in animal experiments. These volleys were of higher amplitude when the cathode was 7 cm lateral to the vertex rather than 7 cm anterior. There were no differences in conduction time between the two recording sites for D and I waves, when these waves could be identified at the low-thoracic site. 3. Anodal stimuli of 150 V commonly produced a descending volley containing a single peak at both recording sites. Modest increases in stimulus intensity to 225-375 V produced a peak 0.8 ms in advance of the wave of lowest threshold in thirteen subjects and, in seven subjects, further increases produced an additional peak 1.7 ms in advance of the first-recruited wave. The early peaks increased in size with stimulus intensity, replacing the first-recruited wave. These results suggest that the site of impulse initiation with electrical stimulation of the motor cortex shifts from superficial cortex to deep structures, approximately 5 and 10-11 cm below the cortex. These sites are probably the internal capsule and the cerebral peduncle. 4. With cathode at the vertex and anode over the 'hand area' the response of lowest threshold occurred at the latency of the anodal D wave but could not be recorded at the low-thoracic site, suggesting that it was generated by the anode over the 'hand area'. Slightly higher intensities induced a 'cathodal D wave' and still higher intensities produced late peaks at latencies of anodal I waves. These cathodal D and I waves involved axons innervating lumbar segments. There was no evidence that cathodal stimulation preferentially produced I waves. Cathodal stimulation at the vertex with the anode 7 cm anteriorly produced similar results: D waves were produced at relatively low intensities, but I waves appeared at relatively high stimulus intensities if at all.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213578 TI - Development of the arterial chemoreflex and turnover of carotid body catecholamines in the newborn rat. AB - 1. The peripheral, arterial chemoreceptors in the carotid body are active and responsive in the fetus. At birth, when oxygenation increases, the chemoreceptors are silenced. Over the next few days the sensitivity is reset toward the adult level and the chemoreceptors influence breathing during normal conditions. In order to investigate the underlying mechanisms of this resetting we examined the strength of the chemoreflex in newborn rats and correlated this to the contents of dopamine and noradrenaline in the carotid bodies of the newborn pups and near term fetuses. Furthermore, turnover rates of dopamine and noradrenaline were determined in newborn rats up to 1 week of age by analysis of catecholamine decreases after inhibition of synthesis with alpha-methyl-p-tyrosine. 2. Chemoreceptor influence was assessed by the method of 'physiological chemodenervation' with hyperoxia of 15-20 s duration in unanaesthetized rat pups. Relative changes in ventilation elicited by hyperoxia were determined by body plethysmography. We found no change in ventilation on the day of birth either in vaginally born rats or in near-term pups delivered by Caesarean section. After 1 day there was a significant decrease in ventilation of -19.4 +/- 2.3% (mean +/- S.E.M.) and at 7 days of age the decrease was -28.8 +/- 2.2%, suggesting an increasing influence from the peripheral chemoreceptors. 3. The contents of dopamine and noradrenaline were measured by high-performance liquid chromatography. Dopamine increased from 3.7 +/- 0.4 pmol (pair of carotid bodies) 1 in the fetus to a peak of 15.9 +/- 2.6, 6-12 h after birth followed by a decline to 7.1 +/- 0.7 at 7 days of age. Noradrenaline levels increased from 1.3 +/- 0.3 in the fetus to 9.6 +/- 1.1 pmol (pair of carotid bodies)-1 after 4 days. The turnover rate of dopamine decreased from 4.4 pmol (pair of carotid bodies)-1 h-1 0-6 h after birth to 1.0 at 6-12 h of age. The turnover rate of noradrenaline also decreased over the first hours following delivery. 4. Since dopamine is an inhibitory neuromodulator in this system, we suggest that the increase in sensitivity seen after the first day of life is, at least in part, due to a decrease in the release of dopamine and thus a removal of an inhibitory mechanism. PMID- 2213581 TI - Excitation of the corticospinal tract by electromagnetic and electrical stimulation of the scalp in the macaque monkey. AB - 1. The responses evoked by non-invasive electromagnetic and surface anodal electrical stimulation of the scalp (scalp stimulation) have been studied in the monkey. Conventional recording and stimulating electrodes, placed in the corticospinal pathway in the hand area of the left motor cortex, left medullary pyramid and the right spinal dorsolateral funiculus (DLF), allowed comparison of the actions of non-invasive stimuli and conventional electrical stimulation. 2. Responses to electromagnetic stimulation (with the coil tangential to the skull) were studied in four anaesthetized monkeys. In each case short-latency descending volleys were recorded in the contralateral DLF at threshold. In two animals later responses were also seen at higher stimulus intensities. Both early and late responses were of corticospinal origin since they could be completely collided by appropriately timed stimulation of the pyramidal tract. The latency of the early response in the DLF indicated that it resulted from direct activation of corticospinal neurones: its latency was the same as the latency of the antidromic action potentials evoked in the motor cortex from the recording site in the DLF. 3. Scalp stimulation, which was also investigated in three of the monkeys, evoked short-latency volleys at threshold and at higher stimulus intensities these were followed by later waves. The short-latency volleys could be collided from the pyramid and, at threshold, had latencies compatible with direct activation of corticospinal neurones. The longer latency volleys were also identified as corticospinal in origin. 4. The latency of the early volley evoked by electromagnetic stimulation remained constant with increasing stimulus intensities. In contrast, with scalp stimulation above threshold the latency of the early volleys decreased considerably, indicating remote activation of the corticospinal pathway below the level of the motor cortex. In two monkeys both collision and latency data suggest activation of the corticospinal pathway as far caudal as the medulla. 5. The majority of fast corticospinal fibres could be excited by scalp stimulation with intensities of 20% of maximum stimulator output. Electromagnetic stimulation at maximum stimulator output elicited a volley of between 70 and 90% of the size of the maximal volley evoked from the pyramidal electrodes. 6. Electromagnetic stimulation was also investigated in one awake monkey during the performance of a precision grip task. Short-latency EMG responses were evoked in hand and forearm muscles. The onsets of these responses were approximately 0.8 ms longer than the responses evoked by electrical stimulation of the pyramid.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213582 TI - Cell swelling, co-transport activation and potassium conductance in isolated perfused rabbit kidney proximal tubules. AB - 1. Isolated, perfused rabbit proximal tubules were used to study the effects of activation of the apical membrane sodium co-transporters, and of the effects of osmotically induced cell swelling, upon cell volume, basolateral membrane potential and apparent partial conductance of potassium. 2. Activation of electrogenic apical sodium co-transport caused a depolarization of the basolateral membrane and a reduction of the basolateral apparent potassium transference number. This was followed by a spontaneous partial recovery of potential and increase in apparent potassium transference number. 3. Stimulation of apical sodium co-transport led to a sustained increase in cell volume. 4. A sustained increase in cell volume (of similar magnitude to that seen after activation of apical membrane sodium co-transporters) was also caused by reduction of bath and perfusate osmolality by removal of 89 mmol l-1 mannitol from both lumen and bath solutions. 5. This reduction in bath and perfusate osmolality also led to a basolateral membrane hyperpolarization and an increase in basolateral apparent potassium transference number. 6. These observations support the possibility that some of the partial recovery of basolateral membrane potential (Vb1) during apical sodium co-transport stimulation is due to a cell volume sensitive change in basolateral potassium conductance. PMID- 2213583 TI - A group II-activated ascending tract of lumbosacral origin in the cat spinal cord. AB - 1. Electrophysiological investigations have revealed a population of ascending tract neurones originating in the lumbosacral enlargement, with input from group II muscle afferents of the cat hindlimb. 2. Single-unit microelectrode recordings were made in the lateral funiculus at L6, from the axons of thirty-four ascending tract neurones. All of the axons were antidromically activated by stimulation of the ipsilateral lateral funiculus at Th13 and, whenever tested (eight units), at C1. 3. Conduction velocities of the axons, between the L6 and Th13 segment, ranged from 33 to 92 m s-1 (mean 61 m s-1). 4. All of the ascending tract neurones were discharged following electrical stimulation of muscle nerves at group II strength, but not by weaker stimuli in the group I range. Most of the investigated neurones were excited by group II afferents of more than one muscle nerve. In addition, a proportion of the units tested could also be discharged by cutaneous and by joint afferents. 5. Responses to natural stimuli were investigated in eighteen ascending tract neurones discharged by electrical stimulation of group II afferents in the gastrocnemius-soleus (GS) and plantaris (P1) nerves which were dissected free in continuity with their muscles. Seven units were spontaneously active. Eight units responded to isometric contraction of the GS/P1 muscles with a discharge occurring mainly on the falling phase of muscle tension. Nine units increased their discharge frequency in response to stretching of the muscles and five units responded to mechanically probing the muscles with a blunt instrument. 6. The final termination sites of this group of ascending tract neurones has yet to be determined. Initial attempts (three units) to antidromically activate the neurones from the cerebellum have been unsuccessful. Other likely areas of termination in the brain stem are considered. PMID- 2213584 TI - The effects of bumetanide, amiloride and Ba2+ on fluid and electrolyte secretion in rabbit salivary gland. AB - 1. In order to distinguish between models of anion secretion, the effects of transport inhibitors on saliva flow rate and electrolyte composition were studied during the plateau phase of secretion in rabbit mandibular salivary glands. 2. Bumetanide, an inhibitor of Na+,K+,2Cl- co-transport, inhibited flow rate (by 60%) and reduced Cl- concentration. K+ and HCO3- concentrations were increased. Forskolin, an adenylate cyclase activator which inhibits ductal transport, did not significantly affect this pattern of changes. 3. Amiloride, used at concentrations that would inhibit Na(+)-H+ exchange, inhibited flow rate (by 30%). Cl- concentration was initially increased before subsequently decreasing at the same time as HCO3- concentration increased. These concentration changes can probably be attributed to ductal transport. When amiloride was applied to glands perfused with nominally HCO3- -free solutions, inhibition of flow rate was rapid and almost complete. 4. When amiloride and bumetanide were both present in the perfusate, flow rate was inhibited by 92%. The pattern of electrolyte changes was not significantly different from that observed in the presence of bumetanide alone. 5. Inhibition of K+ channel activity using Ba2+ also inhibited flow rate. Cl- concentration was increased as was K+ concentration. HCO3- concentration was not increased. 6. The anion exchange inhibitor DIDS (4,4' diisothiocyanatostilbene-2,2'-disulphonic acid) had no effect on either flow rate or electrolyte concentration. It did, however, elicit secretion in the absence of acetylcholine. 7. The data suggest that Na(+)-H+ and Cl- -HCO3- exchangers are unlikely to be involved in fluid and electrolyte secretion in these glands as suggested by some authors. Most of the data can be explained by postulating the existence of non-specific anion channels in the apical membranes of the acinar cells. PMID- 2213585 TI - Increased airway reactivity in the guinea-pig follows exposure to intravenous isoprenaline. AB - 1. Intravenous infusion of (+/-) isoprenaline (1-100 micrograms kg-1 h-1) enhanced airway responses (resistance, RL; and compliance, Cdyn) to histamine (1.0-1.8 micrograms kg-1) and bombesin (100-240 ng kg-1), whereas airway responses to vagal stimulation remained unchanged. 2. Bilateral vagotomy before intravenous infusion of (+/-)isoprenaline (100 micrograms kg-1 h-1) prevented development of airway hyperreactivity to histamine or bombesin, yet vagotomy after infusion of isoprenaline was without effect. 3. Prior treatment with atropine (1 mg kg-1) did not influence the capacity of (+/-)isoprenaline (100 micrograms kg-1 h-1) to increase airway reactivity to bombesin. 4. Despite a 500 fold difference in spasmolytic potency in vivo, infusion of (+)isoprenaline (100 micrograms kg-1 h-1) or (-)isoprenaline (100 micrograms kg-1 h-1) increased reactivity of the airways to histamine or bombesin to a comparable extent. 5. Neither adrenaline (100 micrograms kg-1 h-1) nor forskolin (600 micrograms kg-1 h 1) increased reactivity of the airways to histamine or bombesin. 6. Intravenous infusion of dopamine (100 micrograms kg-1 h-1) or noradrenaline (100 micrograms kg-1 h-1) increased reactivity of the airways to histamine or bombesin. 7. Intravenous infusion of (+/-) propranolol (100 micrograms kg-1 h-1) increased reactivity of the airways to histamine or bombesin which was partially inhibited by bilateral vagal section. 8. Depletion of circulating platelets by lytic anti platelet serum or concomitant infusion of an antagonist of platelet-activating factor (PAF), ginkgolide B (1 mg kg-1 h-1) did not diminish the capacity of (+/ )isoprenaline (100 micrograms kg-1 h-1) to induce hyperreactivity of the airways to histamine or bombesin. 9. These observations indicate that (+/-)isoprenaline can induce airway hyper-reactivity by a mechanism unrelated to beta-adrenoceptor activation, but which is dependent upon intact vagus nerves. PMID- 2213586 TI - Effects of muscarine and adrenaline on neurones from Rana pipiens sympathetic ganglia. AB - 1. Neurones dissociated from Rana pipiens paravertebral sympathetic ganglia were studied by means of the whole-cell patch-clamp technique. Responses to agonists were best recorded when cyclic AMP was included in the patch pipette. 2. Two populations of cells were identified on the basis of size (input capacitance, Cin) and the presence or absence of a fast, transient outward current (A-current, IA). This current was usually present in the 'large' cells (Cin = 40.5 +/- 1.5 pF, n = 66) but absent from 'small' cells (Cin = 21.0 +/- 0.8 pF, n = 70). 3. Both cell types exhibited a slowly activating, non-inactivating K+ current (M current, IM) which was suppressed by luteinizing hormone-releasing hormone (LHRH, 10-100 microM). Threshold for activation of IM was about -75 mV, half-maximal activation was at -50 mV and the M-conductance GM increased e-fold for at 7 mV change in membrane potential. The maximum value for IM studied in large cells by patch-clamp procedures was less than 0.2 nA. More M-channels were available per unit membrane area in the small cells (GM = 1495 microS cm-2) than in the large cells (GM = 1034 microS cm-2). Time constants for IM deactivation at -70 mV were faster in the large cells (37.2 +/- 4.6 ms, n = 16) than in the small cells (66.1 +/- 5.9 ms, n = 9). 4. Muscarine (10 microM) produced inward current in the large cells as a result of IM suppression. In 40% of the large cells, some of the M channels were also sensitive to adrenaline (10-100 microM). In a few large cells (less than 10%) adrenaline produced outward current by increasing IM. 5. Muscarine failed to effect IM in the small cells and instead produced an inwardly rectifying K+ current which activated within 5 ms at -110 mV. The outward current produced in twenty out of thirty-seven small cells by adrenaline was occluded by that produced by muscarine, suggesting that both agonists affect the same K+ channels. 6. Inclusion of the protein kinase inhibitors, 1-(5-isoquinolinyl sulphonyl)-2-methyl piperazine (H-7, 50 microM) or gold sodium thiomalate (GST, 50 microM) in the pipette solution failed to antagonize either muscarine-induced current. Both currents were prolonged when the 'internal solution' contained GTP gamma-S (50 microM). 7. Phorbol-12-myristate-13-acetate (PMA, 2-5 microM) produced an inward current as a result of IM suppression in both small and large cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213587 TI - Acute effects of neomycin on slowly adapting type I and type II cutaneous mechanoreceptors in the anaesthetized cat and rat. AB - 1. Slowly adapting type I (SAI) and type II (SAII) mechanoreceptors in the skin were studied in anaesthetized cats and rats employing mechanical stimuli every 30 s. Individual stimuli rose within 200 ms to a plateau force which was kept constant through a feedback control unit for 2000 ms. 2. In cats, close arterial infusion of neomycin (2.5 mg/min) as sulphate was given through a side branch into the femoral blood stream for 5, 10 or 20 min at a rate of 0.025 ml/min. At other times saline was infused at the same rate. 3. After 20 min of neomycin infusion (total 50 mg) nervous discharge of cat SAI receptors was suppressed to about 30% of the control responses before neomycin infusion. Nervous responses were reduced more profoundly during the plateau phase of stimulation than during the dynamic phase. The interspike interval histogram was severely distorted. 4. In contrast, cat SAII receptors maintained about 70% of their control response after 20 min of neomycin infusion. The interspike interval histogram showed an orderly shift towards longer intervals maintaining its normal shape. 5. In rats, intradermal microinfusion of neomycin (30 micrograms/min) through a glass micropipette into the immediate vicinity of the receptor under investigation resulted in severe transient suppression of SAI receptor responses to about 10% of the control level. Receptor responses recovered almost completely about 1 h after the end of neomycin application. 6. It is concluded that the observed differences between the two types of slowly adapting mechanoreceptors are consistent with the hypothesis that the SAI receptor functions as a secondary sensory receptor, with a synaptic link between the Merkel cell and the primary afferent neurone. PMID- 2213588 TI - Activation of unmyelinated afferent fibres by mechanical stimuli and inflammation of the urinary bladder in the cat. AB - 1. We examined the functional properties of unmyelinated primary afferent neurones innervating the pelvic viscera in twenty-five anaesthetized cats. The axons were isolated from the intact dorsal root and the intact or chronically de efferented ventral root of the segment S2. All units were electrically identified with electrical stimulation of the pelvic nerve. 2. The responses of the neurones were studied with natural stimulation of the urinary bladder using innocuous and noxious increases of intravesical pressure and at the onset of an acute artificial inflammation induced by intraluminal injection of mustard or turpentine oil. 3. Out of 297 unmyelinated afferent units isolated from the dorsal root, seven were excited by an increase of the intravesical pressure during contractions and distension of the urinary bladder. These units were silent when the bladder was empty and had thresholds of 30-50 mmHg which are presumed to be noxious. Further increases of the intravesical pressure were accurately encoded by the discharge rate of the fibres. Out of sixty-eight unmyelinated afferent units isolated from the ventral root none was activated by these stimuli. 4. Intraluminal injection of mustard oil excited mechanosensitive units at short latency. The discharge was not closely related to changes of the intravesical pressure and the units displayed on-going activity after the irritant had been removed. This observation suggests that the units had also chemosensitive properties and that the receptive endings were located in the bladder wall. 5. In sixteen cats ninety-five afferent fibres that were not activated by noxious mechanical stimuli of the urinary bladder were systematically tested with intraluminal injections of mustard oil. This excited 7/67 dorsal root units and 4/28 ventral root units with short latency. Intraluminal application of turpentine oil, tested on twenty-six afferents in four animals, did not produce a rapid excitation. 6. Following the induction of an inflammation some previously non-mechanosensitive units started to respond to changes of intravesical pressure in the biologically relevant pressure range of the urinary bladder. 7. In conclusion, a small subpopulation (2.4%) of unmyelinated visceral afferents responds to high, presumably noxious, intravesical pressure and intraluminal application of chemical irritants. Acute inflammation excites a larger proportion of afferents (9.5%) that are not activated by acute noxious mechanical stimulation of the normal urinary bladder. In the inflamed bladder some previously non-mechanosensitive units started to respond to increases of intravesical pressure. These novel types of chemosensitive receptors may contribute considerably to the pathogenesis of visceral pain states. PMID- 2213589 TI - The role of [Ca2+]i and [Ca2+] sensitization in the caffeine contracture of rat myocytes: measurement of [Ca2+]i and [caffeine]i. AB - 1. Fluorescence measurements have been made in single, isolated rat ventricular myocytes using the Ca2(+)-sensitive indicators Fura-2 and Indo-1. In Fura-2 loaded cells, the application of caffeine (2-20 mM) produced a change of fluorescence indicating an increase of [Ca2+]i which then spontaneously decayed to control levels. These changes of [Ca2+]i were accompanied by a contracture. 2. In contrast, in Indo-1-loaded cells, in addition to the changes of fluorescence expected for the transient increase of [Ca2+]i produced by caffeine, there was a maintained decrease of fluorescence. 3. Measurements in vitro showed that caffeine quenches the fluorescence of Indo-1 (but not of Fura-2) in a [Ca2+]-and wavelength-independent manner. Caffeine therefore had no effect on the ratio of Indo-1 fluorescence measured at two wavelengths. This inhibition by caffeine could be described by an apparent Ki of 4 mM. In the cell the Ki was considerably larger (18 mM). 4. We have separated the Indo-1 fluorescence changes into caffeine- and [Ca2+]i-dependent components. The time course of change of intracellular caffeine was calculated. When [caffeine]o was rapidly increased, [caffeine]i changed with a rate constant of 8 s-1 giving an apparent permeability to caffeine of 2 x 10(-3) cm s-1. 5. This method was used to measure [caffeine]i and [Ca2+]i simultaneously during caffeine-induced contractures. The shape of the caffeine contracture was found to depend on both the speed of application of caffeine and the concentration applied. If caffeine was applied quickly then the contracture developed within 1 s to a maximum level and then relaxed to a lower maintained level. With slower application, there was a more complete relaxation of the initial contraction followed by a slower redevelopment of contraction. 6. Despite the difference in contraction time course, irrespective of the flow rate, [Ca2+]i decayed monotonically. The slow secondary development of contraction has the same time course as the increase of [caffeine]i. The caffeine contracture can be reproduced by a model in which both [Ca2+]i and [caffeine]i affect contraction. 7. The increase of [Ca2+]i is not greatly affected by altering the caffeine concentration from 2.5 to 50 mM. In contrast the maintained level of contraction increases over this range showing that the Ca2(+)-independent effects of caffeine on the myofilaments have a low affinity for caffeine. PMID- 2213590 TI - Effects of caffeine on calcium release from the sarcoplasmic reticulum in frog skeletal muscle fibres. AB - 1. Resting myoplasmic [Ca2+] and [Ca2+] transients (delta [Ca2+]) were monitored using Fura-2 fluorescence and Antipyrylazo III absorbance signals from voltage clamped segments of cut frog skeletal muscle fibres in the presence and absence of 0.5 mM-caffeine. The rate of release (Rrel) of calcium from the sarcoplasmic reticulum was calculated from delta [Ca2+]. 2. delta [Ca2+] and Rrel were increased in caffeine for all pulses. The decline of delta [Ca2+] was slower after a given pulse in caffeine than without caffeine. Resting [Ca2+] was slightly elevated in caffeine. 3. The voltage dependence of the peak value of Rrel and of the steady level of Rrel at the end of a 60-120 ms pulse were both shifted towards more negative voltages in caffeine. For relatively small pulses the voltage at which a given release waveform was observed was also shifted to more negative voltages. 4. Intramembrane charge movements measured in the same fibres in which the above changes in Rrel were observed showed no significant changes in caffeine. 5. In caffeine calcium release continued for many milliseconds after the end of a short (10 ms) pulse. Continued release after a pulse was not observed without caffeine and was probably due to positive feedback of elevated [Ca2+] on calcium release resulting from calcium-induced calcium release in caffeine. 6. Intramembrane charge movements after short pulses showed no change in caffeine that could account for the continued calcium release after the pulse. 7. Continued release after short pulses in caffeine decreased as the pulse duration was increased and was absent for pulses of 60 ms or longer. Rrel also inactivated during such pulses. 8. Relatively large and long conditioning pulses in caffeine suppressed both the peak Rrel and the continued release after short pulses. Peak release and continued release after short pulses recovered in parallel with increasing recovery time following suppression by a conditioning pulse in caffeine. 9. These results indicate that in the presence of caffeine, charge movement and calcium-induced calcium release both contribute significantly to the activation of sarcoplasmic reticulum calcium release during fibre depolarization. Release activated by either mechanism appears to be inactivated by calcium-dependent inactivation. A significant contribution of calcium-induced calcium release during depolarization in the absence of caffeine is not ruled out by present observations. PMID- 2213591 TI - Ionic control of intracellular pH in rat cerebellar Purkinje cells maintained in culture. AB - 1. Intracellular pH (pHi) was measured in single rat cerebellar Purkinje cells maintained in primary culture using microspectrofluorescence analysis of the intracellularly trapped pH-sensitive dye 2',7'-bis-(2-carboxyethyl)-5 (and -6) carboxyfluorescein (BCECF). 2. The ratio of the fluorescence signals measured at 530 nm in response to an alternating excitation at 450 and 490 nm was calibrated using the K(+)-H+ ionophore nigericin. This calibration gave a steady-state pHi of 7.06 +/- 0.02 (S.E.M., n = 17) when cells were perfused by a 5% CO2-25 mM HCO3(-)-buffered solution at an external pH of 7.40 at 37 degrees C. 3. Replacement of external chloride with gluconate in the presence of bicarbonate induced a cytoplasmic alkalinization of about 0.3 pH unit. This alkalinization was independent of external sodium and was greatly reduced by 0.5 mM-DIDS, indicating the presence of a chloride-bicarbonate exchange. 4. In bicarbonate free (HEPES-buffered) solution the steady-state pHi was 7.37 +/- 0.02 (n = 19), significantly higher than in bicarbonate-buffered solution. Recovery from an intracellular acid load brought about by the ammonium chloride pre-pulse technique was blocked by the removal of external sodium or the addition of 1.5 mM amiloride, indicating the presence of a sodium-hydrogen exchange. 5. In bicarbonate-buffered solution pHi recovery after an acid load was also completely blocked by addition of 1.5 mM-amiloride indicating the absence of a bicarbonate dependent acid extrusion mechanism. 6. Addition of 12-O-tetradecanoylphorbol-13 acetate (TPA, 100 nM) induced an amiloride-sensitive alkalinization of about 0.3 pH unit in bicarbonate-buffered solution but had no effect in HEPES-buffered solution. This observation suggests that in cultured Purkinje cells the sodium hydrogen exchanger could be activated through a protein kinase C pathway only when pHi is maintained at a low physiological value by the activity of the chloride-bicarbonate exchange. PMID- 2213592 TI - Regulation of the intracellular free calcium concentration in single rat dorsal root ganglion neurones in vitro. AB - 1. Simultaneous whole-cell patch-clamp and Fura-2 microfluorimetric recordings of calcium currents (ICa) and the intracellular free Ca2+ concentration ([Ca2+]i) were made from neurones grown in primary culture from the dorsal root ganglion of the rat. 2. Cells held at -80 mV and depolarized to 0 mV elicited a ICa that resulted in an [Ca2+]i transient which was not significantly buffered during the voltage step and lasted long after the cell had repolarized and the current ceased. The process by which the cell buffered [Ca2+]i back to basal levels could best be described with a single-exponential equation. 3. The membrane potential versus ICa and [Ca2+]i relationship revealed that the peak of the [Ca2+]i transient evoked at a given test potential closely paralleled the magnitude of the ICa suggesting that neither voltage-dependent nor Ca2(+)-induced Ca2+ release from intracellular stores made a significant contribution to the [Ca2+]i transient. 4. When the cell was challenged with Ca2+ loads of different magnitude by varying the duration or potential of the test pulse, [Ca2+]i buffering was more effective for larger Ca2+ loads. The relationship between the integrated ICa and the peak of the [Ca2+]i transient reached an asymptote at large Ca2+ loads indicating that Ca2(+)-dependent processes became more efficient or that low affinity processes had been recruited. 5. Inhibition of Ca2+ influx with neuropeptide Y demonstrated that inhibition of a large ICa produced minor alterations in the peak of the [Ca2+]i transient, while inhibition of smaller currents produced corresponding decreases in the [Ca2+]i transient. Thus, inhibition of the ICa was reflected by a change in the peak [Ca2+]i only when submaximal Ca2+ loads were applied to the cell, implying that modulation of [Ca2+]i is dependent on the activation state of the cells. 6. Intracellular dialysis with the mitochondrial Ca2+ uptake blocker Ruthenium Red in whole-cell patch-clamp experiments removed the buffering component which was responsible for the more efficient removal of [Ca2+]i observed when large Ca2+ loads were applied to the cell. 7. When cells were superfused with 50 mM-K+, [Ca2+]i transients recorded from the cell soma returned to control levels very slowly. Pharmacological studies indicated that mitochondria were cycling Ca2+ during this sustained elevation in [Ca2+]i. In contrast, [Ca2+]i transients recorded from cell processes returned to basal levels relatively rapidly. 8. Extracellular Na(+)-dependent Ca2+ efflux did not significantly contribute to buffering [Ca2+]i transients in dorsal root ganglion neurone cell bodies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213593 TI - Superposition of H reflexes on steady contractions in man. AB - 1. The aim of the investigation was to study the influence of steady isometric contractions on H reflexes of human soleus muscle. 2. Stimulating and recording conditions were hardly affected by plantar flexions which subjects maintained in a force matching task. 3. If the interval between a preceding control and the test stimulus was less than 8 s the test H reflex was depressed in the relaxed subject. The depression was diminished or removed if the test reflex was superimposed on a background activity. The interval between control and test H reflex was at least 8 s in the following experiments. 4. H reflexes were nearly independent of steady plantar flexions on which they were superimposed. In some subjects, there was a slight increase with increasing torque. During dorsal flexions, H reflexes in all subjects were inhibited with increasing torque. 5. The relationship between test H reflexes, control H reflexes and background activity was evaluated by varying pseudo-randomly stimulus intensity and steady flexion torque. The surface defined by this three-dimensional relation approximated a plane suggesting linear properties of the H reflex. In some subjects threshold intensity decreased slightly with torque, in others it was constant. 6. In response to a warning signal, human subjects initiated steady plantar or dorsal flexions in both feet and, at the same time, they started to concentrate on a light at the onset of which they performed a unilateral ballistic plantar contraction as fast as possible. The relations between H reflex and maintained flexion force during the warning period of the reaction time task were identical to those during force matching, showing that the behavioural context did not modulate the relations. 7. The relations were also the same if reflexes were evoked bi- or unilaterally, illustrating the absence of a mutual modification of simultaneously evoked H reflexes. 8. The relation was the same with ipsilateral matching and relaxed contralateral muscles as with bilateral matching. If the ipsilateral side stayed flaccid contralateral matching increased H reflexes by about 20% above control values. 9. It was concluded that various factors can combine to produce an increase of H reflexes with torque, the most important of them being the use of short intervals between H reflexes. We have various evidence from the present experiments for believing that, in the relaxed subjects, the subliminal fringe was small and that although stimulus intensities below threshold could evoke an afferent volley, the effect of this on low threshold motor units was prevented by presynaptic inhibition at the Ia terminals. PMID- 2213594 TI - The influence of temperature on mechanics of red muscle in carp. AB - 1. We measured the influence of temperature on maximum velocity of shortening (Vmax) of red muscle in carp in order to better understand the influence of temperature on locomotory performance. 2. A stable red muscle bundle preparation containing about 100 muscle fibres was developed. The bundles could not be activated directly by electrical stimulation, but rather contained sufficient nervous tissue so that acetylcholine released from the nerve terminals caused activation of the muscle. A high level of activation was achieved (116 kN/m2) by adding a combination of a 1 mM-caffeine and 10(-5) g/ml eserine to physiological Ringer solution and electrically stimulating the preparation. 3. Force-velocity characteristics were determined at 10 and 20 degrees C by the force clamp method. The data were well fitted by a hyperbola not constrained to pass through P0 = 1 (where P0 is the isometric force). The mean Vmax at 10 degrees C was 3.55 +/- 0.26 muscle lengths/s (ML/s) (n = 6) and at 20 degrees C, 5.71 +/- 0.29 ML/s (n = 6). The mean Q10 for Vmax was 1.63 +/- 0.07 (n = 6). The a/P0* (Hill constant) and Po* (where P0* is the extrapolated load at zero velocity) were 0.49 +/- 0.06 (n = 6) and 1.19 +/- 0.04 (n = 6) respectively at 10 degrees C and 0.29 +/- 0.06 (n = 6) and 1.51 +/- 0.20 (n = 6) respectively at 20 degrees C. 4. The mean Q10 for maximum isometric tension was 1.13 +/- 0.02 (n = 6). The maximal power generation was 59.7 +/- 2.3 W/kg (n = 6) at 10 degrees C and 94.3 +/- 3.2 W/kg (n = 6) at 20 degrees C representing a Q10 of 1.58. The Q10 is less than the product of Q10s for P0 and Vmax because of the greater curvature of the force-velocity curve at 20 degrees C. 5. The 1.63-fold higher Vmax at 20 degrees C than at 10 degrees C enables fish to swim with a 1.6-fold faster muscle shortening velocity, V, at the higher temperature. Thus at both 10 and 20 degrees C, red muscle is used only over the same narrow range of V/Vmax (0.18-0.36), where isolated muscle experiments suggest that power and efficiency are maximal. Thus V/Vmax appears to be an effective design constraint which limits the range of velocities over which muscle is used in vivo at different temperatures. PMID- 2213595 TI - Agonist-dependent Ca2+ and Mn2+ entry dependent on state of filling of Ca2+ stores in aortic smooth muscle cells of the rat. AB - 1. The properties of intracellular Ca2+ stores of intact- and of saponin-skinned A7r5 (an established cell line from embryonic rat aorta) smooth muscle cells were studied by measuring 45Ca2+ and 54Mn2+ fluxes. 2. Application of 5 microM vasopressin to intact cells increased the fractional loss of 45Ca2+ in Ca2(+) free solution by a factor of 5.2. This effect was not influenced by a pre incubation with 10 microM-ryanodine. Caffeine (25 mM) did not stimulate the fractional loss of 45Ca2+ from intact cells. 3. In skinned cells 10 microM-IP3 (inositol 1,4,5-trisphosphate) and 5 microM-A23187 (a calcium ionophore) released the same amount of 45Ca2+. This release did not require GTP and was not affected by a pre-incubation with 10 microM-ryanodine. Caffeine (25 mM) did not release stored Ca2+. 4. NaF (1 mM) plus 10 microM-AlCl3 inhibited by 72% the 45Ca2+ uptake by the IP3-sensitive store of skinned cells at 0.15 microM-Ca2+. Cyclic AMP-dependent protein kinase did not stimulate this ATP-dependent 45Ca2+ uptake, nor could the presence of phospholamban be demonstrated immunologically. 5. The 45Ca2+ uptake by cells which had been depleted of Ca2+ with 5 microM-vasopressin was 69% higher than the uptake obtained without such proceeding depletion. This enhanced 45Ca2+ uptake did not occur through voltage-operated Ca2+ channels, because blockade of these channels with verapamil, or depolarization of the plasma membrane by increasing [K+] from 5.9 to 59 mM in the presence of verapamil, did not modify this uptake. 6. A similar increase of the 54Mn2+ uptake occurred in intact cells with a depleted Ca2+ store. If, however, the cells were first skinned and subsequently exposed to 54Mn2+, the ATP-dependent 54Mn2+ uptake amounted to less than 6% of the ATP-dependent 45Ca2+ uptake. 7. If intact cells were first exposed to a 45Ca2(+)- or 54Mn2(+)-containing solution, and subsequently skinned in a non-radioactive intracellular solution, the addition of 10 microM-A23187 to these cells released stored Ca2+ or Mn2+. The amount of released Ca2+ was only slightly larger than the amount of released Mn2+. If the intracellular store was depleted before loading, the amount of Ca2+ or Mn2+ released by the ionophore increased by 68 and 28%, respectively. 8. It is concluded that A7r5 smooth muscle cells do not express a Ca2(+)-induced Ca2+ release mechanism, but do contain an IP3-induced Ca2+ release mechanism which can release approximately all intracellularly accumulated 45Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213596 TI - The role of adenosine in exercise hyperaemia of the gracilis muscle in anaesthetized cats. AB - 1. A number of metabolites have been proposed to control the vascular tone of skeletal muscle during exercise. The present study was designed to investigate the role of adenosine in this response by determining the effect of the adenosine receptor antagonist 8-phenyltheophylline. 2. The gracilis muscle of anaesthetized cats was exposed and made to contract by stimulating the obturator nerve (at 1 Hz, 5 V, 0.1 ms) for 20 min. Gracilis muscle blood flow and tension were measured during exercise and for 20 min following exercise. Initially this was performed in each animal during the infusion of a vehicle solution (50% polyethylene glycol 400, 50% 0.1 M-NaOH, 0.1 ml min-1 I.V.). Exercise was then repeated during infusion of either further vehicle (group I), 8-phenyltheophylline (group II) or 3-propylxanthine (group III), both at 2.7 x 10(7) mol min-1 kg-1. 3. In group 1 (n = 4) gracilis muscle blood flow during the first exercise period increased by 47.5 +/- 11.3 ml min-1 (110 g)-1 and gracilis muscle tension by 8.6 +/- 1.3 kg (100 g muscle mass)-1 at 20 min of exercise. These responses were not significantly different when repeated. 4. In group II (n = 5), blood flow increased by 46.9 +/- 9.9 ml min-1 (100 g)-1 and tension by 6.5 +/- 0.7 kg (100 g muscle mass)-1 during vehicle infusion. Infusion of 8-phenyltheophylline at a rate which abolished the vasodilatation response to 2-chloroadenosine, significantly reduced the muscle blood flow increase to 19.8 +/- 2.7 ml min-1 (100 g muscle mass)-1 (P less than 0.05) but the tension response was unaffected (increased by 7.0 +/- 0.8 kg (100 g muscle mass)-1). 8-Phenyltheophylline did not affect gracilis muscle blood flow or tension at rest. 5. Administration of 3 propylxanthine, which did not modify the vasodilatation response to 2 chloroadenosine, failed to alter the vascular responses to muscle contraction. 6. These results suggest that activation of adenosine receptors can contribute to up to 40% of the vasodilatation observed during isometric twitch contraction of the gracilis muscle of cats. PMID- 2213597 TI - Deoxygenation permeabilizes sickle cell anaemia red cells to magnesium and reverses its gradient in the dense cells. AB - 1. Our findings of a low total magnesium content in the dense fraction (over 1.118 g ml-1) of sickle cell anaemia (SS) red cells seemed inconsistent with the low Mg2+ permeability and outward Mg2+ gradient seen in normal red cells, and prompted studies of the Mg2+ permeability and equilibria in the SS cells. 2. Deoxygenation and sickling induced Mg2+ permeabilization in SS cells, supporting non-specificity of the sickling-induced cation permeabilization, previously described for Na+, K+ and Ca2+. The extent of Mg2+ permeabilization was comparable in SS cells with normal or high density. 3. Compared with normal density SS cells and normal red cells, the dense SS cells showed a much larger increase in the fraction of ionized magnesium ([Mg2+]i) on deoxygenation, resulting in [Mg2+]i levels sufficient to reverse the normal inward direction of the transmembrane Mg2+ gradient. 4. The molar ratio of 2,3-diphosphoglycerate (2,3-DPG) to haemoglobin was markedly reduced in the dense SS cells. Since 2,3 DPG and ATP are the main cytoplasmic Mg2+ buffers, their further reduction upon binding to deoxyhaemoglobin accounts for the high [Mg2+]i in the deoxygenated dense SS cells; the resulting outward electrochemical Mg2+ gradient, together with sickling-induced Mg2+ permeabilization, could explain the decreased total magnesium content of these cells. 5. The above findings suggested that the documented low sodium pump fluxes in dense SS cells may result from an increased Mg2+:ATP ratio, which is known to inhibit Na(+)-K+ exchange fluxes through the sodium pump. If so, deoxygenation, by increasing the Mg2+:ATP ratio, should inhibit the pump further, whereas increasing ATP should relieve the inhibition. Experiments designed to test this possibility showed that in these dense SS cells, the ouabain-sensitive K(86Rb) influx was low in oxygenated cells, was reduced further by deoxygenation, but was substantially increased after treatment with inosine, pyruvate and phosphate to increase their organic phosphate pool. These results were thus consistent with such a mechanism for Na+ pump inhibition in the dense SS cells. PMID- 2213598 TI - Functional and structural differences in febrile mechanism between rabbits and rats. AB - 1. Febrile responsiveness of rabbits and rats to intravenous (I.V.) or intracerebroventricular injection of human recombinant interleukin-1 alpha (IL-1 alpha), human recombinant interleukin-1 beta (IL-1 beta) and prostaglandin E2 was examined. 2. The I.V. injection of both IL-1 alpha and IL-1 beta produced dose dependent fever over a range of 0.05-2.0 micrograms/kg. A small dose of IL-1 alpha (0.5 micrograms/kg) or IL-1 beta (0.5 micrograms/kg) produced a monophasic patterned fever in both rabbits and rats. A large dose (2.0 micrograms/kg) of IL 1 alpha or IL-1 beta produced a biphasic fever in rabbits, but monophasic fever in rats. Febrile responses in rabbits induced by I.V. injection of IL-1 alpha or IL-1 beta were significantly greater than those in rats induced by these same injections. Furthermore, in both species, the pyrogenicity of I.V. IL-1 beta was greater than that of IL-1 alpha. 3. The intracerebroventricular injection of both IL-1 alpha and IL-1 beta produced dose-dependent fever over a range of 0.2-20 ng. In rabbits and rats, the ventricular injections of IL-1 alpha and IL-1 beta produced fever with almost the same pattern--monophasic, regardless of injection doses. Although febrile responsiveness of rabbits to ventricular injection of IL 1 alpha was greater than that of rats, responsiveness to IL-1 beta was almost the same in both species. Pyrogenicity of ventricular IL-1 beta was greater than that of IL-1 alpha. However, febrile responses in rats induced by ventricular injections of several doses (2-2000 ng) of prostaglandin E2 were greater than those in rabbits. 4. The present results show that febrile responsiveness of rabbits to I.V. IL-1 is significantly greater than that of rats. However, fever sensitivity within the central nervous system (CNS) of rats is not lower compared with that of rabbits. Therefore, we considered that between the two species there exist structural differences in the organum vasculosum laminae terminalis (OVLT), which is currently believed to be the pathway of pyrogen to the CNS and/or the site of production of pyrogenic prostaglandins. 5. Histological examinations showed that the rabbit's OVLT has two vascular components with capillaries, one in the layer near the third ventricle and the other in the layer near the subarachnoideal space. However, the rat's OVLT only has a single component, in the layer near the subarachnoideal space.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213599 TI - Neurones in a discrete region of the nucleus tractus solitarius are required for the Breuer-Hering reflex in rat. AB - 1. The Breuer-Hering reflex consists of a shortening of inspiration and lengthening of expiration in response to afferent input from slowly adapting pulmonary stretch receptors (SAR). We hypothesized that neurones in a discrete region of the nucleus tractus solitarius (NTS) are required for producing the reflex. Accordingly, the present studies were undertaken to: (1) identify sites in the NTS in which chemical excitation of neurones inhibited phrenic nerve discharge in a manner consistent with SAR activation, (2) determine whether localized interruption of synaptic transmission prevented the Breuer-Hering reflex, and (3) determine whether these regions contained pump cells and SAR terminal afferents. Studies were carried out in urethane-anaesthetized rats. 2. Injection of picomoles of an excitatory amino acid, DL-homocysteic acid (DLH), in the NTS, at the rostrocaudal level of the area postrema and immediately medial to the tractus solitarius, silenced phrenic nerve activity similarly to that expected from SAR activation. These apnoeas lasted from 3 to 43 s and were produced with little or no change in arterial pressure or heart rate. 3. The Breuer-Hering reflex, physiologically activated by maintaining lung inflation, was transiently impaired by interruption of synaptic transmission following injections of cobalt chloride in the DLH-responsive region. 4. Pump cell (SAR interneurone) and SAR afferent activity were recorded at the site in which DLH produced apnoea. 5. Taken together, the results of chemical excitation, interruption of synaptic transmission and extracellular recording, suggest that cells within a discrete region of the NTS, probably pump cells, are necessary for the production of the Breuer-Hering reflex. PMID- 2213600 TI - A bladder-to-bladder cooling reflex in the cat. AB - 1. Reflex effects of cold stimulation of the lower urinary tract were studied in cats anaesthetized with alpha-chloralose. The bladder and the urethra were catheterized for separate fluid instillations and the bladder pressure was monitored together with the evoked efferent nerve responses in pelvic nerve filaments. 2. A bladder cooling reflex could be evoked from both the bladder and the urethra. The response was an efferent discharge in preganglionic pelvic motor fibres to the bladder. 3. Bladder mechanoreceptors that drive the normal micturition reflex were not directly involved in the cooling reflex. Their tension sensitivity was decreased by cooling and the efferent reflex response typically occurred before any activation of these receptors. The efferent activity of the cooling reflex also survived an intentional unloading of the mechanoreceptors, a manipulation that abolishes the normal micturition reflex. 4. The dynamic threshold temperature of the cooling reflex was about 30-32 degrees C, which was at the thermal neutral point of the bladder in our experimental situation. 5. The bladder-evoked component of the reflex was greatly reduced or abolished by an intravesical infusion of the local anaesthetic Xylocaine. It was also abolished by total bladder denervation. 6. The vesical component of the reflex was unchanged by bilateral transections of the hypogastric nerves but abolished by pelvic nerve transection. The cooling reflex from the distal urethra was abolished by transection of the pudendal nerves. 7. It was proposed that the cooling reflex originates from cold receptors in the bladder and urethral walls and that the responsible afferent fibres are unmyelinated C fibres. The function of the reflex may be to rid the body of a thermal ballast when under cooling stress. PMID- 2213602 TI - Use-dependent changes in synaptic efficacy in rat prefrontal neurons in vitro. AB - 1. An in vitro slice preparation of rat prefrontal cortex was used to analyse the responses of layer V pyramidal cells to electrical stimulation of layer II. We also studied the long-lasting modifications of synaptic efficacy following high frequency stimulation of the same region. 2. Stable intracellular recordings were obtained from forty-three regular spiking pyramidal cells. The input resistance was 56 +/- 18 M omega (mean +/- S.D.) at a resting membrane potential of -71 +/- 4 mV. 3. At rest, a single stimulus of increasing strength evoked a monophasic, purely depolarizing postsynaptic potential (PSP) of increasing amplitude. In neurons recorded with potassium acetate-filled micropipettes, membrane depolarization disclosed an excitatory-inhibitory (EPSP-IPSP) sequence (onset latency of the EPSP, 3.6 +/- 0.6 ms). 4. Superfusion with the non-N-methyl-D aspartate (NMDA) receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) reduced the EPSP and suppressed the IPSP. The small EPSP which remained was blocked by the NMDA receptor antagonist, D,L-2-amino-5-phosphonovalerate (APV). 5. In five cells, administration of 0.5 mumol l-1 bicuculline revealed a postsynaptic NMDA component in the evoked response as evidenced by its anomalous voltage dependence in the presence of Mg2+ and its sensitivity to APV. In these cells the latency of the APV-sensitive EPSP was the same as that of the APV insensitive EPSP. 6. In six cells superfused with a high-Mg2+, low-Ca2+ artificial cerebrospinal fluid (ACSF) a small monosynaptic EPSP remained which had the same latency as the PSP recorded in control ACSF. 7. Patterned high frequency stimulation (50-100 Hz) was applied to the afferents of twenty-eight neurons (twenty-three of them were recorded in the presence of bicuculline). During the train the membrane potential depolarized some 20 mV and each stimulus evoked a small PSP. The tetanic stimulation was followed by a short-term enhancement of the PSP amplitude and a slight increase in membrane input resistance. 8. Out of the twenty-eight cells, twenty-four showed long-lasting (over 30 min) modifications of the PSP. Long-term depression (LTD) of the evoked PSP was observed in fourteen cells and long-term potentiation (LTP) in ten cells. There was no significant change in the steady-state membrane properties and in the latency of the response. 9. In 64% of the cells that showed LTD and 70% of those that showed LTP of synaptic efficacy, the latency of the enhanced or depressed component of the PSP was the same as the control.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213603 TI - Glucose uptake and transport in contracting, perfused rat muscle with different pre-contraction glycogen concentrations. AB - 1. Glucose uptake and transport, muscle glycogen, free glucose and glucose-6 phosphate concentrations were studied in perfused resting and contracting rat skeletal muscle with different pre-contraction glycogen concentrations. Rats were pre-conditioned by a combination of swimming exercise and diet, resulting in either low (glycogen-depleted rats), normal (control rats) or high (supercompensated rats) muscle glycogen concentrations at the time their hindlimbs were perfused. 2. Compared with control rats, pre-contraction muscle glycogen concentration was approximately 40% lower in glycogen-depleted rats, whereas it was 40% higher in supercompensated rats. Muscle glycogen break-down correlated positively (r = 0.76; P less than 0.001) with pre-contraction muscle glycogen concentration. 3. Glucose uptake during contractions was approximately 50% higher in glycogen-depleted hindquarters than in control hindquarters; in supercompensated hindquarters it was 30% lower. When rats with similar muscle glycogen concentrations were compared, glucose uptake in hindquarters from rats that had exercised on the preceding day was approximately 20% higher than in hindquarters from rats that had not exercised on the preceding day. 4. Muscle membrane glucose transport, as measured by the rate of accumulation of 14C-3-O methylglucose in the contracting muscles, was 25% lower in supercompensated than in glycogen-depleted muscles at the onset as well as at the end of the 15 min contraction period. 5. Intracellular concentrations of free glucose and glucose-6 phosphate were higher at rest and during the entire 15-min stimulation period in supercompensated muscles than in glycogen-depleted muscles, and glucose uptake during contractions correlated negatively with free glucose (r = -0.52; P less than 0.01) as well as with glucose-6-phosphate (r = -0.49; P less than 0.01) concentrations. 6. It is concluded that: (a) The rate of glucose uptake in contracting skeletal muscle is dependent on the pre-contraction muscle glycogen concentration. Regulating mechanisms include limitations of membrane glucose transport as well as of glucose metabolism. (b) Contractions on the preceding day have a stimulating effect on glucose uptake during contractions of the same muscles on the next day. PMID- 2213601 TI - Characteristics of transient outward currents in single smooth muscle cells from the ureter of the guinea-pig. AB - 1. Two kinds of transient outward currents were observed upon depolarization of single smooth muscle cells isolated from guinea-pig ureter. The major transient outward current was through Ca2(+)-activated K+ channels (IK(Ca) which had a large conductance (130 pS; 126 mM [K+]i/5.9 mM [K+]o). 2. The smaller transient outward current (ITO) was pharmacologically separated from other membrane currents in the presence of 1 mM-Cd2+ and 2 mM-tetraethylammonium(TEA+) and was selectively blocked by 3 mM-4-aminopyridine. It peaked (approximately 200 pA) within 10 ms upon depolarization from -80 to +20 mV and its half-inactivation time was approximately 50 ms at +20 mV. Half-maximum voltages (V 1/2) for activation and inactivation were about -8 and -50 mV, respectively, in the presence of 1 mM-Cd2+ and 2 mM-TEA+. The time course of recovery from inactivation of ITO was fitted with a single-exponential function (tau = 100 ms at -80 mV). A tenfold change of [K+]o resulted in a 53 mV change in the reversal potential of the tail of ITO. 3. Cadmium reduced peak ITO and shifted the voltage dependence of activation and inactivation in the positive direction in a concentration-dependent manner. The V 1/2 for inactivation in the absence of Cd2+ was estimated to be approximately -64 mV. 4. Single-channel outward currents which appeared only in the initial part of a depolarizing pulse from about -100 mV were recorded using the cell-attached patch clamp. The decay of the ensemble average of the current was similar to the macroscopic ITO under whole-cell clamp. When the holding potential was less negative, the opening probability of the channel greatly decreased. The channel conductance in normal extracellular medium was 14 pS. 5. In ureter cells ITO resembles A-type current. ITO does not contribute significantly to the repolarization of the action potential but it may regulate membrane excitability by opposing Ca2+ current activated around the threshold of the action potential. PMID- 2213604 TI - Proprioceptive guidance of human voluntary wrist movements studied using muscle vibration. AB - 1. The alterations in voluntary wrist extension and flexion movement trajectories induced by application of vibration to the tendon of flexor carpi radialis throughout the course of the movement, together with the associated EMG patterns, have been studied in normal human subjects. Both extension and flexion movements were routinely of a target amplitude of 30 deg and made against a torque load of 0.32 N m. Flexor tendon vibration consistently produced undershooting of voluntary extension movements. In contrast, voluntary flexion movements were relatively unaffected. 2. The degree of vibration-induced undershooting of 1 s voluntary extension movements was graded according to the amplitude (0.75, 1.0 and 1.5 mm) of flexor tendon vibration. 3. As flexor vibration was initiated progressively later (at greater angular thresholds) during the course of 1 s voluntary extension movements, and the period of vibration was proportionately reduced, so the degree of vibration-induced undershooting showed a corresponding decline. 4. Varying the torque loads (0.32, 0.65 and 0.97 N m) against which 1 s extension movements were made, and thereby the strength of voluntary extensor contraction, produced no systematic changes in the degree of flexor vibration induced undershooting. 5. Analysis of EMG patterns recorded from wrist flexor and extensor muscles indicated that vibration-induced undershooting of extension movements resulted largely from a reduction in activity in the prime-mover rather than increased antagonist activity. The earliest reductions in extensor EMG commenced some 40 ms after the onset of vibration, i.e. well before voluntary reaction time; these initial responses were considered to be 'automatic' in nature. 6. These results support the view that the central nervous system utilizes proprioceptive information in the continuous regulation of moderately slow voluntary wrist movements. Proprioceptive sensory input from the passively lengthening antagonist muscle, presumably arising mainly from muscle spindle I a afferents, appears to be particularly important and to act mainly in the reciprocal control of the prime-mover. PMID- 2213605 TI - Rapid co-transport of sodium and chloride ions in giant salivary gland cells of the leech Haementeria ghilianii. AB - 1. Double-barrelled Cl(-)-selective microelectrodes were used to measure the apparent intracellular Cl- activity (aiCl) and membrane potential (Em) of leech salivary gland cells. In standard physiological solution buffered with HEPES (10 mM), intracellular Cl- activity (corrected for interference) was 38 +/- 8 mM (n = 11) compared to a value of 12.8 mM expected for passive Cl- distribution. The mean Em was -49.4 +/- 8.2 mV (n = 21) which was about 27 mV negative to the Cl- equilibrium potential. 2. Removal of external Cl- led to a slow fall in aiCl until a steady-state level of 4-11 mM was reached in 30-60 min. Recovery of aiCl on readdition of external Cl- took only 2-3 min. The uptake followed an exponential time course having a single rate constant of 1.73 +/- 0.1 min-1 (n = 5) whereas the loss appeared to occur in two phases. Changes in external Cl- produced immediate changes in Em which were the opposite of those expected for a high Cl- permeability, i.e. Cl- removal produced an immediate hyperpolarization (3-18 mV) and readdition of Cl- produced a transient depolarization (5-22 mV). 3. The intracellular accumulation of Cl- was dependent on the external Cl- activity. Even when the external Cl- concentration was reduced to 3%, the cells accumulated Cl- against an electrochemical gradient. 4. Cl- accumulation was temperature sensitive (Q10 approximately 2). 5. On removal of external Na+, aiCl fell to a level which was close to that expected for passive distribution. The active reaccumulation of Cl-, after intracellular Cl- depletion, was abolished in the absence of external Na+; aiCl slowly increased to its passive level. Steady-state aiCl or its recovery by Cl(-)-depleted cells was not affected by the absence of K+ in the bathing solution. 6. The reaccumulation of Cl- was not affected by furosemide (1-5 mM), bumetanide (10(-4) M), amiloride (10(-3) M) or 4-acetamido 4'-isothiocyanostilbene-2,2'-disulphonic acid (SITS, 10(-4) M). 7. Removal of external Cl- caused a fall in intracellular Na+ activity (aiNa, measured with Na(+)-selective microelectrodes) from 15.9 +/- 6.8 mM (n = 9) to 2.5 +/- 1.3 mM (n = 3). When external Cl- was readded, aiNa rose to 46.5 +/- 6.6 mM (n = 3) before slowly recovering towards its original value. The maximal change in aiNa was 41.7 +/- 4.5 mM (n = 3) and the rate constant for Na+ uptake was 1.8 +/- 0.4 min-1 (n = 3).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213606 TI - Brain stem regions mediating the cardiovascular responses elicited from the posterior cerebellar cortex in the rabbit. AB - 1. In this study we have examined the roles of the lateral parabrachial nucleus (lateral PBN) and nucleus tractus solitarius (NTS) as sites mediating the circulatory responses evoked from lobule IX b of the posterior cerebellar vermis in the decerebrate and anaesthetized decerebrate rabbit. Microinjection of either kainic acid or bicuculline into the lateral PBN and NTS was undertaken to assess the importance of neurones and GABAergic mechanisms, respectively, in expressing the cardiovascular responses evoked from lobule IX b. 2. In both the decerebrate and anaesthetized decerebrate rabbit activation of neurones within the lateral PBN with a microinjection of glutamate elicited tachycardia and a pressor response together with an increase in renal sympathetic nerve discharge and vasoconstriction in the hindlimb. A microinjection of GABA into the lateral PBN evoked an opposite pattern of response. Chemical lesioning of neurones within the rostral region of the lateral PBN or pharmacological blockade of GABAA receptor, abolished or significantly attenuated the cardiovascular response (bradycardia/depressor effect) evoked from lobule IX b in the anaesthetized decerebrate rabbit. 3. In the decerebrate animal the tachycardia/pressor response elicited from lobule IX b was suppressed when either kainic acid or bicuculline was microinjected into the caudal division of the lateral PBN. 4. A bradycardia, depressor response, an abolition of on-going renal nerve activity and vasodilatation in the femoral bed were evoked by activating neurones within a restricted region of the NTS with glutamate in the decerebrate and anaesthetized decerebrate rabbit. A microinjection of GABA into the NTS produced a qualitatively opposite pattern of response. The bradycardia/depressor response evoked from lobule IX b in the anaesthetized decerebrate rabbit was not altered significantly following a microinjection of either kainic acid or bicuculline into the ipsilateral NTS. However, in the decerebrate preparation following a microinjection of bicuculline into the ipsilateral NTS the tachycardia/pressor response evoked from IX b was either abolished or in many cases reversed to the pattern of response seen in the anaesthetized decerebrate rabbit. 5. The present experiments provide evidence for two functionally distinct pathways from the cardiovascular region of lobule IX b to the lateral PBN.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213607 TI - Inhibition of barosensitive neurones evoked by lobule IXb of the posterior cerebellar cortex in the decerebrate rabbit. AB - 1. Electrical stimulation of lobule IXb of the posterior cerebellar vermis evoked an increase in heart rate and arterial pressure in the decerebrate rabbit. This pattern of response was followed by a rebound bradycardia which was maintained until arterial pressure had returned to control levels. Activation of the arterial baroreceptors during IXb stimulation failed to elicit reflex changes in heart rate and arterial blood pressure. 2. Extracellular recordings were made from eighty-one single neurones in the nucleus tractus solitarius (NTS), and adjacent structures, that received inputs from the carotid sinus nerve, aortic nerve and/or vagus. A proportion of these were characterized as baro- or chemosensitive by physiological stimuli. The nature of the input from lobule IXb onto these cells was studied subsequently. 3. In twenty-seven out of thirty-five barosensitive neurones, stimulation of lobule IXb either decreased or abolished on-going activity. The latency to onset of inhibition was 21 ms in fourteen cells. In a further twenty-one neurones the spikes evoked orthodromically by electrical stimulation of either the aortic or sinus nerves were either inhibited or severely reduced in number during short-train conditioning stimulation of lobule IXb. This effect was most potent when the cortical conditioning stimulus was timed to occur 25 ms before the aortic or carotid sinus nerves were stimulated. 4. It is suggested that stimulation of lobule IXb in the decerebrate rabbit expresses its influence on the cardiovascular system in part by an inhibitory action on neurones receiving baroreceptor inputs at the level of the NTS. PMID- 2213608 TI - Differentiation of membrane excitability in isolated cleavage-arrested blastomeres from early ascidian embryos. AB - 1. Differentiation of excitable cells was studied electrophysiologically and histochemically in cleavage-arrested blastomeres isolated from early ascidian embryos. Blastomeres were isolated at the 4- or 8-cell stage, and cultured in sea water containing cytochalasin B until the time of hatching of control larvae. Electrical responses, immunoreactivity to epidermis-specific monoclonal antibody (2C5) and activity of muscle-specific acetylcholinesterase were examined. 2. All cleavage-arrested blastomeres isolated from an 8-cell embryo differentiated to elicit either muscular- or epidermal-type action potentials, but no neural-type action potentials were observed in these blastomeres. The anterior-animal and the posterior-animal blastomeres developed only epidermal-type action potentials, which involved expression of Ca2+ channels and immunoreactivity to 2C5. One-third of anterior-vegetal blastomeres developed epidermal-type action potentials which are mediated by Ca2+ channels though the immunoreactivity to 2C5 was absent. A majority of remaining blastomeres showed action potentials composed of Ca2+ currents and TEA-sensitive delayed K+ currents (type I response), and a few of them had fast transient K+ currents (A-currents) in addition (type II response). One-third of posterior-vegetal blastomeres developed epidermal-type action potentials without expression of the immunoreactivity to 2C5. The remainder differentiated into muscular-type cells, which expressed Ca2+ currents, TEA sensitive and TEA-insensitive delayed K+ currents, and showed acetylcholinesterase activity. 3. Cleavage-arrested blastomeres isolated from a 4 cell embryo also differentiated into epidermal- or muscular-type cells, but not neural-type cells. The anterior blastomere, which is the parent cell of anterior animal and anterior-vegetal blastomeres of an 8-cell embryo, developed epidermal type, type I or type II responses, as was the case in the anterior-vegetal blastomere isolated from an 8-cell embryo. The posterior blastomere, which was the parent cell of posterior-animal and posterior-vegetal blastomeres of an 8 cell embryo, differentiated into either epidermal-type or muscular-type cells in terms of both membrane excitability and immunochemical reactivity. 4. Cleavage arrested 1-cell embryos differentiated exclusively into epidermal-type cells in terms of membrane excitability and 2C5 immunoreactivity, even when the cytochalasin B concentration was decreased below 0.1 microgram/ml.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213609 TI - Induced neural-type differentiation in the cleavage-arrested blastomere isolated from early ascidian embryos. AB - 1. Isolated blastomeres and pairs of blastomeres from 8-cell embryos of Halocynthia roretzi and Halocynthia aurantium were cleavage-arrested with cytochalasin B and cultured. Their differentiation was examined in terms of membrane excitability, immunoreactivity to an epidermis-specific monoclonal antibody (2C5), and the presence of acetylcholinesterase. 2. The blastomeres that showed epidermal-type differentiation had Ca2(+)-dependent action potentials and membrane currents, and immunoreactivity to 2C5. The blastomeres that showed neural-type differentiation had Na(+)-, Ca2(+)- and TEA-sensitive delayed K+ channels, and lacked immunoreactivity to 2C5. 3. Cleavage-arrested anterior animal blastomeres, a4-2, when cultured in isolation from an 8-cell embryo, differentiated exclusively into epidermal-type cells. However, when cultured in contact with anterior-vegetal blastomeres, A4-1, they mostly showed neural-type differentiation (seventeen out of twenty-four cells in H. roretzi). 4. Reduction of the cytochalasin B concentration enhanced neural-type development of a4-2 blastomeres in contact with A4-1 blastomeres in H. aurantium, possibly by tightening the physical contact between the blastomeres. 5. When a cleavage arrested and isolated a4-2 blastomere was treated with 2% pronase at 10 degrees C for 15 min at the time when sister control embryos reached the 32-cell stage, the blastomere underwent neural-type differentiation in a manner identical to that of a4-2 blastomeres contacted by A4-1 cells. 6. The period during which neural-type differentiation of a4-2 blastomeres could be induced by treatment with pronase was from the 8-cell to the 110-cell stage. At the late gastrula stage neural-type differentiation of a4-2 blastomeres was not induced by pronase. The effective period for neural-type differentiation of a4-2 blastomeres in contact with A4-1 cells was between the 64-cell stage and late gastrula stage. Competence of the a4 2 blastomere to undergo neural-type differentiation decreased during gastrula stages, while the inducing ability of the A4-1 blastomere lasted longer. 7. In a few cases the posterior-animal blastomere, b4-2, could also be induced to undergo neural-type differentiation after contact with A4-1 cells or after pronase treatment. 8. The appearance of Na+ spikes in a4-2 blastomeres in contact with A4 1 cells was considered a manifestation of neural induction, similar in principle to the induction of ectoderm by the chorda-mesoderm in higher vertebrates. PMID- 2213611 TI - Brush-border membrane alkaline phosphatase activity in mouse Peyer's patch follicle-associated enterocytes. AB - 1. Using a new method of quantitative cytochemistry to determine alkaline phosphatase activity, it was possible to identify M cells and distinguish two further types of enterocytes present in mouse Peyer's patch follicle-associated epithelial tissue. 2. A quantitative description of these three cell types was provided by making direct absorbance measurements of enzyme reaction product on the luminal surface of individual follicle-associated enterocytes. M cells having a negligible alkaline phosphatase activity had a mean absorbance of 6 +/- 2 arbitrary units. The other two populations of enterocytes had overlapping but significantly different mean absorbances of 20 +/- 2 and 30 +/- 3 arbitrary units. 3. M cells accounted for 3.2 +/- 1% of the total number of cells present in the apical part of the follicle-associated epithelium. This percentage is a minimum value describing an extreme example of cells having M cell-like characteristics. The remaining epithelial cells were divided equally between those having high and low alkaline phosphatase activities in their brush-border membranes. A small percentage of cells having low alkaline phosphatase activities could perform M cell functions. 4. Results obtained suggest that reduced alkaline phosphatase activity and brush-border membrane Cl- conductance can both be used as differentiation markers to identify a large population of poorly differentiated enterocytes present in mouse follicle-associated epithelial tissue. PMID- 2213613 TI - Prosthodontics 21. A national symposium on prosthodontics. October 1-6, 1989, Rochester, MN. Proceedings. PMID- 2213610 TI - Chloride conductance and intracellular chloride accumulation in mouse Peyer's patch enterocytes. AB - 1. Measurements of membrane potential, Cl- conductance and intracellular Cl-, K+, Na+ and H+ activities have been carried out in the follicle-associated epithelium of the mouse Peyer's patch to characterize further the physiological properties of antigen-transporting M cells, enterocytes and intraepithelial lymphocytes. 2. Intraepithelial lymphocytes, identified in random impalements as a second negative jump in membrane potential (Vm), were found to have higher K+ and H+ activities, lower Na+ and Cl- activities and higher negative values for Vm than either of the other two epithelial cell types. Cl- activity in these cells was higher than that predicted from the Nernst equation. 3. M cells identified as having the first negative jump in Vm in impalements involving intraepithelial lymphocytes were unable to accumulate Cl-. They also had a lower Vm than that found in apparently fully differentiated enterocytes. This Vm was partly depolarized at a low Cl- concentration. 4. Apparently fully differentiated enterocytes could be further divided into two populations depending on whether the Vm could or could not be partly depolarized by a low Cl- concentration. The mean Vm and intracellular Cl- activity of Cl(-)-sensitive cells, measured in high Cl- medium, were less than values found for Cl(-)-insensitive enterocytes. Cl- was only accumulated by enterocytes showing no depolarization at low external Cl- concentration. 5. The Vm of mature villus enterocytes was the same as that determined for Cl(-)-insensitive follicle-associated enterocytes. Villus enterocyte Vm was not depolarized at a low Cl- concentration. 6. The present ability to distinguish two apparently large populations of follicle-associated enterocytes having M cell-like or villus enterocyte-like properties is discussed in relation to current theories describing how M cells might be formed. The presence of a Cl- conductance in M cell enterocytes, the inability to accumulate Cl- and the maintenance of a low Vm could aid endocytosis of macromolecules across the apical membrane. PMID- 2213614 TI - Prosthodontics. Clinical practice--professional affairs. Review of the literature. PMID- 2213612 TI - Electrophysiology of parasympathetic neurones isolated from the interatrial septum of bull-frog heart. AB - 1. Whole-cell voltage-clamp techniques were used to study the voltage-dependent membrane conductances in parasympathetic neurones enzymatically isolated from the interatrial septum of bull-frog heart and maintained in short-term (1-10 day) tissue culture. 2. The resting potential of the isolated neurones averaged -55.4 +/- 1.1 mV (+/- S.E.M., n = 11). Action potentials evoked in the isolated cells by brief (1-2 ms) current injections were similar to those recorded from neurones in the 'intact' septum. The amplitude of action potentials of isolated neurones averaged about 113 mV, with a peak depolarization of +32.8 +/- 2.8 mV and after hyperpolarization of -80.0 +/- 2.8 mV. 3. The pattern of membrane currents recorded using voltage clamp with 'normal' external (containing 110 mM-Na+) and internal (110 mM-K+) solutions consisted of a rapidly activating and inactivating inward current followed by a slower, sustained outward current. 4. The inward components of current were isolated by using an internal solution in which Cs+ and TEA+ (tetrathylammonium) ions replaced K+. Depolarizations from holding potentials of -50 to -70 mV produced inward currents which had an initial transient phase followed by a maintained, or very slowly inactivating, component. The current-voltage relation for the initial transient phase reached a peak at membrane potentials near 0 mV, while the maintained phase, measured, for example, at the end of 50 ms voltage-clamp steps, had its peak near +10 mV. 5. The transient component of inward current was carried primarily by Na+ ions, as replacement of Na+ by TEA+ in the external solution abolished the transient. This current was thus identified as a voltage-dependent Na+ current, INa. The maintained component was greatly attenuated by removing 80-90% of the external Ca2+ ions, and it was abolished by divalent cations such as Cd2+ (0.2-0.4 mM), Ni2+ (0.5 mM) and La3+ (10-100 microM). This maintained component was thus a voltage-dependent calcium current, ICa. 6. About 80% of INa recorded in the presence of low (0.2-0.5 mM) external Ca2+ and 2 microM-LaCl3 was blocked by tetrodotoxin (TTX) with an apparent Kd of about 8 nM. The remaining 20% of INa was resistant to block by 2-10 microM-TTX. However, the 'TTX-resistant' component of INa was blocked by Cd2+ (0.2-0.4 mM). 7. The voltage-dependent calcium current, ICa, measured in saline in which Na+ was replaced by N-methyl-D glucamine, activated near -40 mV and reached a peak near +10 to +15 mV.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 2213615 TI - Prosthodontics. Clinical practice--delivery of services. Review of the literature. PMID- 2213616 TI - Predoctoral fixed prosthodontics education. AB - All current prosthodontic services will be needed well into the 21st century because millions of people are still without complete dentitions. However, knowledge of current and projected dental health needs indicates that the extent of usage of certain prosthodontic procedures will change because the number of edentulous patients will decrease. Presently there is considerable need and demand for extensive prosthodontic services and the need has been projected to grow. The demand for fixed prosthodontic services will likely increase in the future, particularly with the increased usage of new materials and treatment modalities. Recent data obtained from the American Dental Association Commission on Dental Accreditation indicate that failure rates on Part II of the National Board Dental Examinations and the prosthodontics section of Part II have remained relatively constant from 1980 to 1987. Total Part II failure rates for this time period have only ranged from 8.31 to 9.91 and on the prosthodontics section from 2.10 to 2.74. While these data do not predictably reflect clinical and technical skills or a knowledge of the most current didactic information, they do indicate that adequate knowledge had been provided to predoctoral students regarding the fundamental principles of prosthodontics. However, reductions have been made in prosthodontic curricular time. With the current escalation of knowledge in prosthodontics and allied areas and the increasing time constraints, it is becoming increasingly difficult to teach a thorough understanding of the basics and exposure to new developments. Any further reductions in curricular time will significantly compromise educational quality. PMID- 2213617 TI - Predoctoral removable prosthodontics education. AB - As the 21st century is approached, changes are occurring that directly relate to removable prosthodontics at the undergraduate level. Edentulism will continue to decline, although the need for complete dentures will diminish slowly because of the replacement needs for the existing edentulous population. In the short- to medium-term future, partial edentulism will increase in the older population at the expense of total edentulism. Therefore, the need for removable partial dentures will increase, but subsequently will decline. In the long-term, tooth loss, regardless of etiology, will be reduced. However, the replacement of lost teeth is unlikely to disappear completely as a needed dental service. With 73% of dental schools reporting inadequate or marginal numbers of complete denture patients, Meskin and Entwistle have identified a shortage of patients needing removable prostheses. On the other hand, 50% of the schools report a surplus of removable partial denture patients. Dental school curriculum time related to prosthodontics has declined significantly over the past 20 years. However, over the past 10 years it has risen slightly. Techniques that are taught in dental schools are frequently not being used in practice. Yet the practitioner's interest in removable prosthodontics as it relates to new techniques and materials remains high according to a 1988 survey of Academy of General Dentistry members. Removable prosthodontics was rated first in regards to continuing education courses desired by its members. There are two basic objectives stated in the prologue of the Council on Dental Education Directive on Accreditation Standards. First, faculties are ultimately responsible for the quality of care rendered to the patient population by students.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213619 TI - Continuing dental education in prosthodontics. PMID- 2213618 TI - Advanced education in prosthodontics. AB - 1. The ADA Council on Dental Education Commission on Accreditation, using the Standards for undergraduate education and current National Board scores, does not believe there has been a deemphasis in prosthodontic knowledge and skill. This opinion is not shared by program Directors or representatives of the laboratory industry. The Council on Dental Education has a mechanism for periodic review in place. State Boards of Dental Examiners did not respond. 2. Teaching experience for residents or graduate students should be encouraged in advanced education programs in prosthodontics as an elective or be limited to no more than 10% of the curriculum time. 3. The American Board of Prosthodontics would not comment on any changes regarding the clinical or didactic knowledge of candidates. 4. Meaningful research is not possible within the current minimum 22-month program duration. 5. Accredited advanced education programs in prosthodontics are currently meeting the standard guidelines for clinical and didactic experiences. 6. Accredited advanced education programs in prosthodontics are currently satisfying the requirements on supervision and faculty; however, the data from the annual reports suggest a marked decrease in staff support and amount of time that program directors are devoting to the program. 7. Expanding the curriculum to include implant prosthodontics will require lengthening the curriculum time. 8. TMJ therapy and geriatric dentistry need to be better defined in the educational guidelines. 9. The criterion-based examination currently given by the American Board of Prosthodontics clearly delineates acceptable, marginal, and unacceptable levels of performance. 10. Program directors desire more "feedback" from the American Board of Prosthodontics on the performance of candidates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 2213620 TI - Prosthodontics. Marketing. Review of the literature. PMID- 2213622 TI - "Rewarming patients in the PACU: can we make a difference?". PMID- 2213621 TI - Proceedings of Prosthodontics 21. A national symposium on prosthodontics. PMID- 2213623 TI - Continued contact with a familiar nurse affects women's perceptions of the ambulatory surgical experience: a qualitative-quantitative design. AB - Ambulatory surgery patients tend to have different nurses providing care during each phase of the surgical stay. The purpose of this study was to investigate the impact continued contact with a familiar nurse, from preadmission procedures through postoperative awakening to consciousness in the PACU, had on women's postdischarge evaluations of their ambulatory surgical experience. The study consisted of a convenience sample of 40 women between the ages of 19 and 68 years scheduled to receive general anesthesia. Women in the continued contact group (n = 20) reestablished contact with the familiar nurse when arriving at the ambulatory surgery unit (ASU) 1 hour before surgery and they maintained continued contact with that nurse while awakening to consciousness in the PACU. A postdischarge telephone interview was conducted with women in both groups 3 to 5 days following surgery. chi 2 Analysis found that women who had continued contact with a familiar nurse reported being ready to go home when discharged from the ASU significantly more often than women in the control group (P less than .05). By t test analysis, women in the continued contact group reported greater satisfaction with the nursing care received (P less than .01). Women in both groups also talked about their ambulatory surgical experience. The data are presented descriptively. Findings indicated that receiving continued contact with a familiar nurse significantly affected women's postdischarge evaluations of their ambulatory surgical experience compared with receiving standard nursing care in the study hospital. PMID- 2213624 TI - Exploring nursing interventions for acute pain in the postanesthesia care unit. AB - The postanesthesia nurse encounters patients with pain daily in nursing practice. The intensity of patients' acute postsurgical pain varies from mild to very severe. Currently, the treatment of choice for postsurgical pain is administration of a narcotic, usually in titrated intravenous doses. When the pain is mild and the patient is able to cope until the narcotic reduces the intensity of the pain, narcotics alone are satisfactory. However, the patient with severe pain may not be able to cope with the length of time required for the narcotic administered to produce pain relief. For those patients additional measures are needed to assist them in coping with the pain. Nursing interventions may benefit the adult postanesthesia patient who is experiencing acute pain upon emergence from anesthesia. Physiology of pain transmission and nursing research in the area of acute pain control are the basis for interventions. Preoperative education and sensory preparation, distraction, deep breathing, and progressive muscle relaxation are additional interventions with potential to enhance acute pain control in the PACU. PMID- 2213625 TI - Acute postoperative pain: the cause and the care. AB - Although pain is one of the most difficult phenomena to measure, in recent decades giant steps have been taken in its effective control. A lack of knowledge in the area of pain and inordinate fear of the side effects of analgesic drugs used to treat pain limit the advances in control of postoperative pain. To address this deficiency, this article highlights the important determinants in the control of postoperative pain. Some of the factors that influence an individual's perception of pain will be described. A review of the more commonly used routes and modes of drug administration in such treatment will be presented, followed by a discussion of the side effects, both positive and negative, of the opioids that can be used. Finally, some of these opioid drugs will be described. PMID- 2213626 TI - Postoperative urinary retention: Part I--Overview and implications for the postanesthesia care unit nurse. AB - Postoperative urinary retention and resulting bladder distention are common complications following surgical procedures. The PACU nurse needs a thorough understanding of bladder distention, causes, and how to assess for signs and symptoms in the PACU patient. Unrelieved bladder distention can lead to discomfort and problems with micturation or chronic urinary retention. The anatomy of the bladder, causes and factors related to bladder distention, and methods with which the PACU nurse can assess and evaluate for bladder distention are presented. PMID- 2213627 TI - Postanesthesia care unit extubation protocol based on the Marker Model. AB - In an attempt to clearly define nursing practice in the PACU, nurses and anesthesiologists worked collaboratively to develop an extubation protocol. The protocol is for patients no longer requiring mechanical ventilation and who will be extubated in the PACU. The protocol is unique in that it is written in a format derived from the Marker Model. Using a hierarchical concept, the Marker Model provides a framework for dividing nursing standards into three categories: structure, process, and outcome. While the extubation protocol illustrates an example of a process standard, the article also focuses on briefly describing the major components of the Marker Model and how they interrelate. PMID- 2213628 TI - The beginner's attitude. AB - Communication is often a source of conflict and dissatisfaction. The Beginner's Attitude turns conflict into harmony. We have all learned poor communication habits through misdirected social programming. The average attention span is estimated by psychologists to be only 1% of the time involved in an interaction. Sensitivity and self-help programs identify our inadequacies, but they offer few remedies. Hence, most of us do not know how to improve our communication. The Beginner's Attitude offers specific technology in language that's easy to understand. Learning becomes the motivation for communication and tension dissolves into effortless rapport. The Beginner's Attitude results in sincere and effective communication. PMID- 2213630 TI - Practical points in understanding neuromuscular blockade. AB - The physiology of the neuromuscular junction has a significant impact on the pharmacology of neuromuscular blockade and associated reversal. Depolarizing and nondepolarizing agents for blockade and enzyme inhibitors for reversal of blockade are discussed. Clinical applications are also reviewed. PMID- 2213629 TI - Current and future trends in ambulatory surgery and their impact on nursing practice. AB - The rapidly changing ambulatory surgery arena requires the professional nurse practicing in that area to be constantly aware of practices and policies to meet the demands of providing high-quality care at a low cost. Programs to effectively streamline the ambulatory surgery process as well as enhance the patient's experience will facilitate the success of ambulatory surgery units. This article discusses specific trends in ambulatory surgery and mechanisms to facilitate smooth functioning of the ambulatory surgery unit. PMID- 2213632 TI - The nurse manager and ethical choices. AB - Ethical decision making on issues other than those in the clinical area are presenting a special challenge to today's nurse managers. This article discusses some of these issues and presents a model for use in analyzing them. Frequently used ethical principles are also included. PMID- 2213631 TI - The effects of two warming methods on core and surface temperatures, hemoglobin oxygen saturation, blood pressure, and perceived comfort of hypothermic postanesthesia patients. AB - An experimental study was conducted in two PACUs to test the effect of two warming methods on core and surface temperatures, oxygen hemoglobin saturation, blood pressure, and perceived comfort of hypothermic postanesthesia patients. The study was based by Selye's theory of stress, which states that when individuals are confronted with stressors, physiological adaptation occurs to maintain homeostasis. Subjects studied were 91 adult patients who were randomly assigned to two groups: group 1 patients were warmed with the Bair Hugger Warming System (Augustine Medical, Inc, Eden Prairie, MN), and group 2 patients were warmed with warmed bath blankets. Multiple analysis of variance with repeated measures demonstrated significant differences between the two groups on surface temperature, oxygen hemoglobin saturation, and perceived comfort. No significant differences were found between the two groups on core temperature and blood pressure. Implications for PACU nurses include an efficient, cost-saving method to promote patient adaptation to the stressors of inadvertent hypothermia. Further studies are needed to validate the findings from this study and to test nurses' responses to the Bair Hugger Warming System. PMID- 2213633 TI - Pepper Commission recommends universal health care coverage. AB - Many Americans are without adequate health care as costs continue to rise. Health care insurance is unaffordable or unavailable to over half the working poor, but hospitals can no longer bear the expense of uncompensated care. The United States Bipartisan Commission on Comprehensive Health Care has issued recommendations to Congress entitled "Health Care and Long Term Care for All Americans." The Commission plan proposes a system that would be phased in over several years. This article discusses phases of the system from the first through the fifth year. PMID- 2213634 TI - Writing with clarity. PMID- 2213635 TI - Total and partial sleep deprivation in clomipramine-treated endogenous depressives. AB - Improvement in depression after total sleep deprivation (TSD) is, as a rule, followed by relapse after subsequent ad libitum sleep. This study is addressed to the question of how nocturnal partial sleep following TSD affects this relapse. Thirty endogenously depressed patients participated in the study. During the night after TSD, subjects were allowed sleep during one of three periods, i.e., unlimited sleep (11:00 p.m.-8:00 a.m.), early partial sleep (11:00 p.m.-3:00 a.m.), or late partial sleep (4:00 a.m.-8:00 a.m.). The hypothesis that partial sleep deprivation on the night following TSD prevents relapse has to be rejected. Relapse was inversely related to a drop in minimum rectal temperature during the night with unlimited or partial sleep, compared with minimum rectal temperature on the previous night. PMID- 2213636 TI - Morning or night-time melatonin is ineffective in seasonal affective disorder. AB - Melatonin, at the same doses used to treat circadian-rhythm related sleep disturbances, had no effect on the depressive symptoms in seasonal affective disorder (SAD) patients, whether given early (7 a.m.) or late (11 p.m.) for a week. Slight improvements in sleep were seen with nighttime administration. The circadian rhythmicity of urinary 6-sulphatoxymelatonin was not modified in any way. Melatonin at this dosage (5 mg/day) or at these two times is therefore not a potential alternative treatment for SAD; light remains the therapy of choice. PMID- 2213638 TI - Augmentation of auditory evoked potentials in somatization disorder. AB - Sensory input regulation was examined in terms of augmenting/reducing of auditory evoked potentials in 10 patients with somatization disorder (8 males and 2 females) and 10 age- and sex-matched normal controls. The slope of P1-N1 amplitude change as a function of stimulus intensity was greater in patients compared with controls, suggesting an enhanced central nervous system response to sensory input. Taken together with previous findings of a failure to habituate to incoming stimuli in a similar group of patients, and evidence obtained in somatizers of both over-responding to background stimuli in a simple tone discrimination task and enhanced parietal activation during selective attention, this finding suggests disturbances in the processes of attention and in the regulation of afferent stimuli in somatization disorder, and may help explain the multiple and chronic complaints characteristic of patients with the disorder. PMID- 2213637 TI - DSM III as a systemic culture pattern: studying intracultural variation among psychiatrists. AB - DSM III is viewed as embodying a pool of information pertaining to a systemic culture pattern of psychiatry and attempts are made to describe how psychiatrists understand and apply it using ideas from cognitive anthropology. Each of seven psychiatrists evaluated a group of patients in an intake setting. Seven broad categories of Axis I diagnoses were formed and the frequencies with which psychiatrists used these categories were computed. In addition, twelve arithmetical measures pertaining to the five axes of DSM III and a current functioning axis and the decision regarding disposition were also computed. Using these dependent variables, the study analyzes the similarities and differences among psychiatrists in the way they formulate intake evaluations. Psychiatrists' selections of Axis I diagnoses were highly intercorrelated but they differed greatly among themselves in the way they coded many of the axes of DSM III. Group correlations among diagnostic measures indicated a patterning among diagnostic measures and the nature of this patterning is discussed. Each psychiatrists' set of correlations among the twelve diagnostic measures was itself correlated with that of others and this showed a very high level of interpsychiatrist agreement. Deductions drawn from the cultural consensus model suggest that psychiatrists share an underlying 'grammar' that references the pool of information pertaining to DSM III. PMID- 2213640 TI - Schizophrenic performance on line bisection: no simple lateralization defects. AB - Many studies have assessed the possible lateralization deficits of schizophrenics, and the results usually suggest left hemisphere dysfunction. Nevertheless, they have been variable. This may have been due to cognitive demand of the different tasks, not to changes in brain lateralization itself. In order to circumvent this problem, the present study evaluates the performance of schizophrenics on a simple but lateralized task, line bisection. Subjects bisected a line using either visual or tactile information, with the left or right hand, when it was placed in their left or right hemispace or directly in front of them. Schizophrenic subjects were not more erroneous than normals (variable error), nor were they biased differently from normals in either direction with either modality of sensory input (constant error). There were only two significant effects of group on the tactile line bisection, one of position x length x group and one of position x hand x end x length x group, both on constant error (directional bias). The lack of main effects and presence of interactions on these basic tasks suggests that apparent lateralization differences found in schizophrenic subjects are due not to a simple defect of brain lateralization but may stem from task demands and attention allocation. PMID- 2213639 TI - Platelet monoamine oxidase activity and evoked response as predictors of anxiety and depression derived from the content analysis of speech. AB - Platelet MAO activity has been reported by several investigators to differentiate schizophrenia, schizophrenia related depressive disorders, alcoholism, unipolar and bipolar depression from normal controls. Evoked potentials likewise have differentiated schizophrenic and affective patients. However, the precise relationship between MAO activity, evoked potentials (EP), and psychiatric illness has not been clarified. A possible association between psychopathology and high MAO activity/EP reducing and low MAO activity/EP augmenting has been reported. Such a bidirectionality further confounds results. This study was undertaken to determine the association of psychopathological dimensions found in a group of subjects whose platelet MAO activity and evoked responses were obtained two years earlier. Utilizing the Gottschalk-Gleser verbal behavior scales of Anxiety, Depression, Social Alienation-Personal Disorganization and Cognitive Impairment a significant correlation was revealed between low platelet MAO activity and high Total Anxiety scale and Shame Anxiety subscale scores. Additionally, a significant correlation was demonstrated between reducing evoked potentials and elevated Death Anxiety, Somatic Concerns, and Total Death and Mutilation Depression subscales scores, combined and separately. Furthermore, a significant positive correlation was found between augmenting evoked potentials and Overt Hostility Outward scores. No significant correlations were demonstrated between platelet MAO activity or evoked potentials and Social Alienation-Personal Disorganization or Cognitive Impairment scores. These findings lend support to the position that biological markers may predict predispositions to anxiety and depression. PMID- 2213641 TI - Paralinguistic characteristics of speech in schizophrenics and depressives. AB - Schizophrenics, depressives, patients with anxiety neurosis and normal controls were asked to comment freely for 2 min on photographs depicting seven facial emotional expressions. Schizophrenics commented for the shortest duration of time with characteristic vocalization; depressives' speech was characterized by low initiative time latency, greater duration of utterance but fewer word-counts. PMID- 2213642 TI - Cerebral metabolic and cognitive studies in dementia with frontal lobe behavioral features. AB - Three subjects with dementia of the Alzheimer type (DAT) with frontal lobe features of behavioral disinhibition were studied using positron emission tomography with [18F]2-fluoro-2-deoxy-D-glucose (18 FDG) and standardized neuropsychological tests. The three subjects showed significant decrements (p less than .05) in relative glucose metabolism (regional/mean gray metabolism) in the orbitofrontal, prefrontal and anterior cingulate regions when compared to healthy controls. Severity-matched subjects with DAT without the associated frontal lobe features did not show the relative reductions in glucose metabolism in these regions when compared to controls. However, on neuropsychological testing of frontal lobe cognitive functions the three subjects did not show decrements that were more severe than those shown by severity-matched DAT patients without the behavioral features. These data demonstrate physiologic dysfunction in specific cortical regions in subjects with behavioral aberrations attributed to these regions and an apparent dissociation between behavioral and cognitive functions of the frontal lobe. PMID- 2213643 TI - Learned resourcefulness, drinking, and smoking in young adults. AB - The purpose of this study was to examine the relationship between learned resourcefulness and two common addictive behaviors, namely, drinking and smoking. Male and female college students (N = 175) completed the Self-Control Schedule (SCS), the Quantity-Frequency-Variability questionnaire, and a smoking history form. Learned resourcefulness was related to self-reported patterns of alcohol consumption; specifically, heavy drinking subjects were lower in learned resourcefulness than were light and moderate drinkers who, in turn, were lower in learned resourcefulness than were infrequent drinkers and abstainers. Learned resourcefulness was only modestly related to smoking, with students who had never smoked evidencing somewhat higher learned resourcefulness than ex-smokers and current smokers. Overall, these data provide correlational support for the notion that learned resourcefulness may protect young adults against substance abuse. PMID- 2213644 TI - Interpersonal style and anxiety. AB - Agoraphobic anxiety has been linked to traditional feminine sex role attitudes and related dyadic interactions. This research correlated measures of panic experience and agoraphobic anxiety with interpersonal style in a college student population. Significant positive correlations were observed between anxiety scores and the following interpersonal styles: submissive/deferent, self effacing/obedient, mistrusting/cold, submissive, inhibited, and unassured. Results lend support to clinical reports that some individuals may develop agoraphobic symptoms as a result of the interaction of interpersonal style with relationship patterns. PMID- 2213645 TI - Perceptions of sexual harassment: a re-examination of gender differences. AB - There is mixed evidence for gender differences in perceptions of sexual harassment. To help clarify the existence of gender differences, we examined the sexual-harassment perceptions of 409 state government employees in the western United States. Few gender differences were found. We also compared the workers' perceptions to findings from a previous study of students (Terpstra & Baker, 1987). The relative ordering of the incidents' perceived severity was very similar, but workers perceived a number of incidents to be more harassing than did students. Thus, the major differences found were between students and workers, not between genders. Potential theoretical and methodological causes of these findings are discussed. PMID- 2213646 TI - Early adolescents' values about their pets. AB - The essays of adolescent boys and girls (N = 354) explaining their decisions to save a pet in the event of a fire were examined by content analysis for the adolescents' underlying value orientations. Hedonistic utility, a moral value characteristic of the second of Kohlberg's (1976) moral development stages, was the primary value underlying adolescents' choices. PMID- 2213647 TI - Content analysis of sexual fantasies of males and females. AB - Content analysis of the sexual fantasies of 87 community college and university students revealed no significant sex differences in the content of sexual fantasies. Both men and women preferred traditional and facilitative fantasies. Because this study was explorative, however, further research is required to validate the suggested scale and replicate these results. PMID- 2213648 TI - Cognitive processing in specifically language-impaired children. AB - Eighteen language-impaired children and 25 non-language-impaired children were evaluated to investigate the relationship between language ability and selected aspects of the five-component problem-solving process defined by Kagan and Kogan (1970). Non-impaired children performed better than language-impaired children on nearly all components of the problem-solving process. Language-impaired children had particular difficulties in the areas of coding and hypothesis generation. In fact, coding ability was inversely related to the number of errors made in hypothesis evaluation. Coding ability was also positively correlated with language ability. The exact causal relationship between coding ability, language ability, and error-making in hypothesis evaluation is unclear; however, improving coding skills through training may increase automaticity and lead to improved performance in the higher levels of the problem-solving process. PMID- 2213649 TI - Granulocyte-macrophage colony-stimulating factor is a growth-factor for promastigotes of Leishmania mexicana amazonensis. AB - In this paper we show that murine lung conditioned medium (LCM) displays, in addition to its already described colony-stimulating activity on bone marrow cells, a potent growth-stimulating activity on promastigotes of Leishmania mexicana amazonesis. Immunoprecipitation of LCM with an antibody specific for murine granulocyte-macrophage colony stimulating factor (GM-CSF) abrogates both activities, indicating that the leishmanial growth-promoting activity is due to the presence of GM-CSF on LCM. Furthermore, recombinant GM-CSF (rGM-CSF) added to the culture medium or to the immunoprecipitated LCM is able to respectively induce or to partially recover the growth-promoting activity of the LCM. Sequential in vitro passages of the parasite induces a progressive loss of sensitivity to the growth-factor. Parasite forms recently collected from lesions are significantly more responsive to the growth-factor than forms already adapted to grow in culture. Since it has been shown that several different microorganisms display receptors for vertebrate-like hormones and that GM-CSF is able to enhance a cutaneous leishmanial lesion, our results permit us to raise the hypothesis that a direct interaction between a host-derived hormone and a pathogenic microorganism can be of importance in defining the fate of an infection. The fact that GM-CSF is produced by cells that actively participate in a leishmanial infection (T-lymphocytes and macrophages) reinforces our hypothesis. PMID- 2213650 TI - Neoglycoproteins as carriers for receptor-mediated drug targeting in the treatment of experimental visceral leishmaniasis. AB - Methotrexate (MTX) coupled to mannosyl bovine serum albumin (BSA) was taken up efficiently through the mannosyl receptors present on macrophages. Binding experiments indicate that conjugation does not decrease the affinity of the neoglycoprotein for its cell surface receptor. The drug conjugate eliminated intracellular amastigotes of Leishmania donovani in mouse peritoneal macrophages about 100 times more efficiently than free drug on the basis of 50% inhibitory dose. Inhibitory effect of the conjugate was directly proportional to the density of sugar on the neoglycoprotein carrier. Colchicine and monensin, inhibitors of receptor-mediated endocytosis, can prevent the leishmanicidal effect of the conjugate. Antileishmanial effect of the conjugate can be competitively inhibited by mannose-BSA and mannan. In a murine model of experimental visceral leishmaniasis the drug conjugate reduced the spleen parasite burden by more than 85% in a 30-day model whereas the same concentration of free drug caused little effect. These results indicate that MTX-neoglycoprotein conjugate binds specifically to macrophages, and is internalized and degraded in lysosomes releasing the active drug to act on Leishmania parasites. These results also represent the potential for a general approach to intracellular targeting of clinical agents for macrophage-associated disorders. PMID- 2213651 TI - Morphology of diplomonad flagellates: Spironucleus torosa n. sp. from Atlantic cod Gadus morhua L., and haddock Melanogrammus aeglefinus (L.) and Hexamita salmonis Moore from brook trout Salvelinus fontinalis (Mitchill). AB - A diplomonad flagellate, Spironucleus torosa n. sp. is described from Atlantic Cod Gadus morhua and haddock Melanogrammus aeglefinus. This is believed to be the 1st confirmed report of Spironucleus from a marine fish. Organisms swimming in the rectal lumen were broadly pyriform to elongate, and measured 10.5-18.6 microns long and 3.2-13.3 microns wide; other elongate organisms were attached to the rectal epithelium, via apical extensions appearing continuous with the microvilli. The posterior end of the body was extended into a caudal projection, on either side of which was a posteriolateral ring-shaped protrusion or torus, with a recurrent flagellum emerging from its centre. A symmetrical system of microtubules and lamellae, forming a "V" in protargol impregnated specimens, supported the flanges of the body surrounding the tori, the tori themselves and the caudal projection. Supranuclear microtubules were an inverted V to U shape in transverse section, and an electron dense band accompanied the cytostomes. Lightly staining homogenous cytoplasm was usually present in the anterior part of the body, the remainder being highly vacuolated with numerous dark granules. In swimming organisms, rough endoplasmic reticulum (RER) was present around the nuclei and cytostomes, and bacteria were occasionally seen in the cytoplasm. In "attached" organisms, RER was reduced, and bacteria were absent. Hexamita salmonis Moore from Salvelinus fontinalis was studied by light and scanning electron microscopy for comparison; its cytoplasm was not highly vacuolated. The two recurrent flagella emerged close together from the blunt posterior end of the body. PMID- 2213652 TI - Glucokinase and fructokinase of Trichomonas vaginalis and Tritrichomonas foetus. AB - Trichomonas vaginalis and Tritrichomonas foetus contain glucokinase and not a hexokinase of broad hexose specificity. Tritrichomonas foetus also contains a specific fructokinase which could be resolved from glucokinase by anion exchange chromatography. Native T. vaginalis glucokinase had a Mr of 76,000, and SDS-PAG electrophoresis showed two equally stained bands corresponding to Mr 40,000 and 38,000. Glucose and ATP were by far the best substrates for both trichomonad glucokinases, with Km values as low as 33-35 microM and 75-83 microM, respectively. Substrate saturation curves for these enzymes were all hyperbolic. Tritrichomonas foetus fructokinase required fructose and ATP, with Km values of 200 microM and 81 microM. None of the activities was affected by a number of potential regulatory metabolites, including glucose-6-phosphate. The only exception was AMP which in supraphysiological concentrations had an inhibitory effect on T. foetus fructokinase. In conclusion, the absence of regulation at the hexose phosphorylation step described here, as well as the presence of an easily reversible PPi: fructose-6-phosphate 1-phosphotransferase described previously (Mertens, E., Van Schaftingen, E. & Muller, M. 1989. Mol. Biochem. Parasitol., 37:183-190), suggest that the rate of the 1st part of glycolysis in trichomonads is controlled only by the intracellular availability of hexoses. PMID- 2213653 TI - Electrophoretic karyotype and linkage groups of the amoeboflagellate Naegleria gruberi. AB - We have constructed a molecular karyotype for two strains of Naegleria gruberi using pulsed field gel electrophoresis. Each strain has about 23 chromosomes, considerably more than any previous estimate. These chromosomes range in size from 400 kilobasepairs to over 2,000 kilobasepairs. In Naegleria, construction of the DNA karyotype depends on assessment of the anomalous electrophoretic mobility of the circular ribosomal RNA genes. We have determined the chromosomal locations of an identified unique gene (flagellar calmodulin) and four identified multigene families (alpha- and beta-tubulin, actin, ubiquitin), as well as three differentially expressed genes of unknown functions. The ca. 12 actin genes are dispersed over at least seven chromosomes, whereas the majority of the more than eight alpha-tubulin genes are confined to a single chromosome. The ubiquitin genes are found on five chromosomes in one strain and seven in the other and the beta-tubulin genes are on three or four. Our observations provide a foundation for molecular genetic studies in this organism. PMID- 2213655 TI - Analysis of Pneumocystis carinii cyst wall. I. Evidence for an outer surface membrane. AB - It has long been thought that the cyst form of Pneumocystis carinii, which can resist host defenses and antimicrobial drugs, is responsible for relapses of P. carinii pneumonia. The thick wall of the cyst is immunogenic and rich in glucosyl/mannosyl and N-acetyl-D-glucosamine residues. In this study we have demonstrated the presence of a hitherto unreported outer membrane in the cyst wall of P. carinii. This membrane was detected by a combination of techniques, including transmission electron microscopy, freeze-fracture electron microscopy, and membrane labeling with fluorescent lipid analogs following treatment of P. carinii cysts from infected rats for 30 min with Zymolyase, a beta-1-3 glucanase. As in gram-negative bacteria and blue-green algae, this 2nd membrane may have an important role in osmoregulation and nutrient utilization; it may also mediate the interaction of P. carinii with its host and serve as a target for drug therapy. PMID- 2213654 TI - Constancy of adenine methylation in Tetrahymena macronuclear DNA. AB - Macronuclear DNA from Tetrahymena was examined in order to determine whether the pattern of adenine methylation changed with the transcriptional activity of nearby genes. The DNA from growing, starved and conjugating cells was digested with six restriction enzymes which are sensitive to methylation of adenine within their recognition site. Southern blots of the restricted DNAs were probed with seven cDNA clones and one genomic clone which are homologous to polyA+ RNAs, whose transcriptional activity varies with the physiological state of the cell. One of the cDNA clones, BC11, had not been described previously. It hybridized to a 1.3 kb transcript which was present in populations of starved and conjugating, but not in growing cells. On Southern blots of genomic DNA it hybridized to a complex pattern of bands which was highly polymorphic between the DNAs of closely related strains. It was estimated that between 137 and 272 sites were assayed for changes in methylation, including at least 27 sites which were known to be methylated. No differences were seen in the size of restriction fragments from cells in different physiological states. The data suggested that the methylation pattern, which is determined during macronuclear development, does not vary with the physiological state of the cell. PMID- 2213657 TI - Sensitivity of female rabbits to changes in photoperiod as measured by pheromone emission. AB - Newborn rabbits are completely dependent on a pheromone on the mother's belly for the release of nipple-search behaviour and suckling. Using the stereotyped behavioural response of the pups as a bioassay it could be shown that: 1. In non breeding does pheromone emission is stimulated by experimental long day and suppressed by experimental short day conditions within 1 to 2 weeks of reversing the light regime. 2. Under constant long day conditions pheromone emission, readiness to mate, conception rate and litter size remain high with no evidence of endogenous seasonal rhythmicity. 3. Experimental changes in daylength of just 1 or 2 h in either direction are sufficient to induce marked alterations in the level of pheromone emission, number of successful matings and average litter size within 2 to 3 weeks. Pheromone emission would thus seem to provide a sensitive test of photoperiodic responsiveness in non-breeding female rabbits, and a convenient, non-invasive indicator of their reproductive state. PMID- 2213656 TI - Analysis of Pneumocystis carinii cyst wall. II. Sugar composition. AB - Pneumocystis carinii cysts are capable of resisting host defenses and antimicrobial drugs and are therefore thought to be responsible for relapses of P. carinii pneumonia in AIDS and other immunocompromised patients. The interaction of P. carinii with its host, and other P. carinii, might be mediated by molecules which form the outer surfaces of this organism. Carbohydrates are known to play many roles in cell-cell adhesion, and have been detected on the surface of P. carinii by lectin labeling experiments. In this study P. carinii cyst wall material was obtained from Zymolyase treatment. Alditol acetate derivatives of neutral and amino sugars or trimethylsilyl derivatives of methyl glycosides were prepared from the monosaccharides released from the sample by acid hydrolysis. Analyses were done by a combination of gas chromatography and mass spectrometry. Glucose was found to be the major sugar constituent. Mannose and galactose were present in equal ratios. A lesser amount of N-acetyl-D glucosamine, and trace amounts of ribose and sialic acid were present in the cyst wall samples analyzed. These sugars may mediate P. carinii-host interaction and play an important protective role by creating a permeability barrier around the cyst. PMID- 2213658 TI - Medullary electrosensory processing in the little skate. I. Response characteristics of neurons in the dorsal octavolateralis nucleus. AB - 1. Ampullary electroreceptors in elasmobranchs are innervated by fibers of the ALLN, which projects to the dorsal octavolateralis nucleus (DON). The purpose of this study is to examine the response characteristics of ALLN fibers and DON neurons to weak D.C. and sinusoidal electric field stimuli presented as local dipole fields. 2. ALLN fibers respond to presentation of D.C. fields with a phasic burst, followed by a more slowly adapting period of firing. Ascending efferent neurons (AENs) in the DON respond to stimuli with a similar initial burst, which adapts more quickly. 3. Type 1, 2, and 3 neurons are possible local interneurons or commissural DON neurons. Type 1 neurons demonstrate response properties similar to those of AENs. Type 2 cells demonstrated slowly adapting responses to excitatory stimuli, the duration of the response increased with the amplitude of the stimulus. Type 3 neurons demonstrated an increased rate of firing, but the response lacked any specific temporal characteristics. 4. ALLN fibers typically have receptive fields consisting of a single ampulla. The receptive field sizes of DON neurons exhibited varying degrees of convergence for different cell types. 5. Responses of ALLN fibers and DON neurons to weak sinusoidal stimuli demonstrated very similar frequency response characteristics for all cell types. The peak sensitivity of electrosensory neurons was between 5 10 Hz. PMID- 2213659 TI - Medullary electrosensory processing in the little skate. II. Suppression of self generated electrosensory interference during respiration. AB - 1. Previous studies have demonstrated that the resting activity of electrosensory ALLN fibers is modulated by the animal's own respiratory activity and that all fibers innervating a single ampullary cluster are modulated with the same amplitude and phase relationship to ventilation. We demonstrate that ALLN fibers in the skate are modulated in this common-mode manner bilaterally, regardless of receptor group, orientation, or position of the receptor pore on the body surface (Fig. 2). 2. Ascending efferent neurons (AENs), which project to the electrosensory midbrain from the DON, are modulated through a much smaller portion of their dynamic range. AENs give larger responses to an extrinsic local electric field than to the respiratory driving, indicating that a mechanism exists for suppressing ventilatory electrosensory reafference. 3. In paralyzed animals no modulation of resting activity or of responses of extrinsic electric fields could be observed with respect to the animal's respiratory motor commands in the absence of electrosensory reafference. 4. Cells of the dorsal granular ridge (DGR) project to medullary AENs via the DON molecular layer. A majority of proprioceptive DGR neurons are modulated by ventilatory activity, however, in a given fish the modulation is not in the same phase relationship to ventilation among DGR units. 5. The modulation of AENs during respiration was increased following transection of the contralateral ALLN (Fig. 9). Resting activity and responses to excitatory stimuli were inhibited by simultaneous stimulation of the transected contralateral ALLN indicating that a common-mode rejection mechanism is mediated via the commissural interconnections of the DONs. PMID- 2213660 TI - When an institution dies. Nursing's role in closing a facility. AB - 1. This article documents the development of a nursing role to support the staff and faculty of a state residential school for adolescents during closure of that institution. 2. The process of institutional closure resulted in increased ambiguity and need to redefine social expectations and responsibilities. Supportive nursing intervention facilitated the transition. 3. Theory and intervention associated with loss through death and dying can be appropriately adapted for use in nursing intervention during loss experienced with organizational death and institutional closure. 4. Because the meaning and experience of loss during institutional closure involves everyone and does not occur in a uniform or linear manner, nurses' roles must be flexible, responsive to contextual change, and introspective, as well as analytical and supportive. PMID- 2213661 TI - Who are they? Identifying and treating adult children of alcoholics. AB - 1. Adult children of alcoholics are frequently found within the population of clients on inpatient psychiatric units. The percentage of this population is greater than the occurrence of ACoAs in the general population. 2. Nursing staff can assist these clients in a therapeutic way by becoming familiar with the types of issues these clients present and the behaviors they manifest. These issues should be reflected in treatment planning. 3. Anger, abuse, guilt, and grief form the core issues that ACoAs must deal with in therapeutic ways during psychiatric hospitalization. PMID- 2213662 TI - Under wraps: prevalence of staff-patient sexual interactions on inpatient units. AB - 1. Fifty-seven percent of the hospitals with inpatient psychiatric units responded to the survey. 2. Out of these hospitals, 23% reported suspicions, 43% allegations, and 23% occurrences of staff-patient sexual interactions within the previous 2 years. 3. Neither the existence of staff educational programs, hospital size, nor ownership status were significant predictors of the number of events. 4. Patient abuse predictors must be identified. PMID- 2213663 TI - Anxiety reduction. Lessons that benefit students and patients. AB - 1. Teaching intrapsychic skills enables the teacher as well as the students/patients to learn these skills. 2. Anxiety level reduction can be achieved through specialized teaching techniques. 3. Incorporating these techniques into the education of nursing students and other mental health professionals would help students and professionals deal with anxiety and burnout on the job. 4. A milieu that incorporates such teaching techniques and principles benefits both patients and staff. PMID- 2213664 TI - Reframe your outlook on recidivism. AB - 1. Deinstitutionalization has placed many chronically mentally ill people in communities that are not prepared to care for them. A lack of fit between clients and the programs provided often results in repeated visits to psychiatric emergency services. 2. Repeated visits to a community program can be viewed positively: community services carry less stigma than hospital admissions, they are less expensive, and they are directly linked with the community. 3. By encouraging a return to a community program before decompensation necessitates a hospital admission, it becomes possible to focus on how a client can cope with, rather than simply react to, the illness. PMID- 2213665 TI - Angela Barron McBride. PMID- 2213666 TI - You are what you read. The use of bibliotherapy to facilitate psychotherapy. AB - 1. In the course of therapy with individuals or couples, it is sometimes helpful to suggest reading specific material to assist in the therapeutic process. 2. It is important that the therapist be totally familiar with the recommended material and have a specific purpose for the recommendation. 3. The therapeutic interaction, rather than the reading of material, is the focus of the treatment. 4. Such reading may prove helpful because it becomes an educational experience and comprehension of a concept is increased; the material can be "validating" when written by someone unknown to the client who has had a shared experience; and it can remove a struggle for control from the therapeutic relationship by giving information or opinions directly to the client. PMID- 2213667 TI - The appreciation of radiation risks. PMID- 2213668 TI - Black looks ... at confidentiality. PMID- 2213669 TI - Atopy and genetics. A review. PMID- 2213670 TI - Clinical problems in patients with prosthetic heart valves. AB - Information from the UK Heart Valve Registry, which was established in 1986 and receives data from all centres in the National Health Service, shows that more than 5,000 artificial heart valves are implanted each year in Britain and that almost two-thirds of these are mechanical. This article is intended as a practical outline of the clinical problems and complications which may occur. PMID- 2213671 TI - Risk prediction in medicine and surgery: ethical and practical considerations. AB - Risk prediction is a subject of increasing clinical interest, and publications in this area are likely to have an important influence on patient care in the near future. A multiplicity of risk prediction systems, many of them computer-based, will raise a number of ethical and practical questions. These questions need to be addressed by the originators of systems, the editors of journals, practising clinicians, and the lay public. PMID- 2213672 TI - Medicine as a career among 1974 and 1977 British medical qualifiers. AB - Information was obtained for about 95% of 1974 and 1977 qualifiers from British/UK medical schools. The percentages giving medicine as a career choice were much lower some years after qualifying than in the pre-registration year. A third of those working in medicine 13 years after qualifying were consultants, but 9 years after qualifying almost 90% of those who had initially given medicine as a first career choice had not become senior registrars or consultants in a medical discipline. Just over 6% of respondents had obtained medical experience abroad at some stage. Only 10 consultants in medical disciplines described having worked in general practice. Among 1974 qualifiers who had been medical registrars, 34% were medical consultants, 6% were consultants in non-medical specialties and 20% were general practitioners, when surveyed 13 years after qualifying. Details are given of individual medical specialties. PMID- 2213673 TI - Who asks permission for an autopsy? AB - A survey was undertaken of all hospitals with more than 400 beds in North East Thames Region to ascertain the way in which permission for an autopsy was obtained, in an attempt to explore reasons for declining autopsy rates. We found that there was a considerable variation in autopsy rates, and in the systems within hospitals whereby permission for autopsy is sought. The responsibility for requesting an autopsy is often delegated to younger doctors who have not received any training in how it should be done. A sensitive lay person can achieve high rates of permission for autopsy. Most consultants interviewed stated that they requested less autopsies now than 5 or 10 years ago. They seldom attended autopsies, and one-third of pathologists have given up contacting the clinician before an autopsy. PMID- 2213674 TI - The health of health care workers. The Ernestine Henry lecture 1990. AB - The health of health care workers is mentioned in the early occupational health literature but the significance of these populations in occupational health has only recently received widespread attention. The health care industry now employs about 5% of the national workforce and, despite its size and the multiplicity of its occupational hazards, little systematic enquiry has taken place to quantify these risks. The occupational health services available to health service staff are often rudimentary. Current health concerns include evidence that the mortality experience of subgroups is not as favourable as for comparable socio economic groups. Specific areas of concern are occupational exposures to biological agents such as HIV and hepatitis B, pharmaceutical products, allergens, violence, electromagnetic fields and chemical carcinogens. Psychosocial factors and excessive hours of work may, in part, explain the high suicide rates experienced by some subsections of the workforce. New initiatives to investigate and monitor this complex working environment are clearly needed. PMID- 2213675 TI - The molecules of cancer. The Watson Smith lecture 1990. PMID- 2213676 TI - The dissemination of multiple sclerosis. The Langdon-Brown lecture 1989. PMID- 2213677 TI - The clinical and scientific basis of drug toxicity. A report of a conference. PMID- 2213678 TI - Medical training and the White Paper. Report of a conference. PMID- 2213679 TI - Gene therapy: myth or reality? Report of a conference. PMID- 2213680 TI - How safe is our food? A report of the British Nutrition Foundation's eleventh annual conference. PMID- 2213681 TI - Hereford and cholera--why did we escape it? PMID- 2213682 TI - Unsullied Wilde. PMID- 2213683 TI - More consultant dermatologists are needed. PMID- 2213684 TI - Teaching genetics to medical students. PMID- 2213685 TI - Black looks ... at when life begins. PMID- 2213686 TI - An analysis of experimental radiation carcinogenesis with model setting for competing risks. AB - The mean life span of animals killed by a specific type of tumor and the incidence of that particular tumor are influenced by competing risks. A parametric approach for censored samples was applied to correct for the competing risks. The life span distribution under each risk wherein the other risks were thought to be eliminated is assumed to be a Weibull distribution. Our data were from an experiment on tumor induction by X-rays in mice: whole body irradiation with 600 R; head with 800 R; trunk with 800 R; or lower body with 800 R. Analysis of the results shows that the mean appearance time of malignant lymphomas was accelerated by whole body irradiation. Acceleration of lung tumors was relatively large after trunk irradiation. Mammary tumors were accelerated by whole body, trunk or lower body irradiation. PMID- 2213687 TI - Effects of 3'-deoxyadenosine (cordycepin) on the repair of X-ray-induced DNA single- and double-strand breaks in Chinese hamster V79 cells. AB - The ability of cordycepin to inhibit the repair of DNA strand breaks was examined with X-irradiated Chinese hamster V79 cells in log-phase culture. A filter elution technique revealed that 70 microM cordycepin did not inhibit the repair of single-strand breaks but inhibited the repair of double-strand breaks. These findings confirmed the fact that the increase in the lethality of cordycepin in X irradiated cultured mammalian cells was attributable to unrepaired DNA double strand breaks. PMID- 2213688 TI - Barley seed radiosensitivity following post-hydration in oxygen-, nitrogen- and nitrous oxide-saturated water. I. Influence of caffeine and t-butyl alcohol. AB - Dry (approximately 3.5 and 4.0 per cent moisture content) barley seeds were exposed to 350 Gy of 60Co- gamma-rays in vacuo and post-hydrated at 4 degrees C for 8 h in O2-, N2-, or N2O-saturated water. The effect of caffeine and t-butyl alcohol (t-BuOH) dissolved in the post-hydration medium on the magnitude of damage developing under these three different gaseous circumstances was studied. The post-irradiation damage and its modification by caffeine and t-BuOH was assessed in terms of 8-day-old seedling injury, peroxidase activity and total peroxides in the 8-day-old seedlings. Post-irradiation O2-saturated hydration caused maximal 8-day-old seedling injury, and increased peroxidase activity with concomitant reduction in total peroxides. Both caffeine and t-BuOH afforded significant radioprotection against post-irradiation O2-dependent damage. Post irradiation N2O-saturated hydration was even more significantly radioprotective than the N2-saturated post-hydration. Under these circumstances, t-BuOH exerted no effect whatsoever on the N2- and N2O-mediated post-irradiation damage. Caffeine, on the other hand, significantly potentiated these two components of damage. A brief consideration of the physicochemical events which possibly account for the observed effects is presented. PMID- 2213689 TI - Rational risk estimation in relation to atomic bomb radiation. AB - This paper summarizes genetic and somatic data on persons exposed to low doses of atomic bomb radiation in Hiroshima and Nagasaki. Compared with experimental estimates, the new dosimetry system proposed in 1986 underestimates neutron doses, supporting qualitatively the conclusion by the 1965 dosimetry system that Nagasaki A-bomb emitted predominantly gamma rays whereas Hiroshima A-bomb emitted both gamma rays and fast neutrons. A theory based on two recessive mutations in hemopoietic stem cells is proposed to explain radiation leukemogenesis. The theory can explain, at least partly, the actual dose-response curve for incidences of acute leukemia in Hiroshima but cannot explain chronic leukemia in Nagasaki. Existence of a large threshold dose in the latter's dose relationship supports the hypothesis that A-bomb radiation at high doses above a threshold value was a promoter and/or progressor of leukemia. Various lines of evidence that support this hypothesis are presented. Hence, it is not warranted to assume that risk of death from cancer at a high dose, say, 1 Gy can be divided by 100 to obtain the risk at 1 cGy. Risk at low doses should be assessed by direct scrutiny of actual data at low doses in spite of their large statistical uncertainty. Actual data show that A-bomb survivors at 1-9 cGy had apparently lower incidences of tumors than unexposed persons. PMID- 2213691 TI - Determination of specific activity of cobalt (60Co/Co) in steel samples exposed to the atomic bomb in Hiroshima. AB - Specific activity 60Co/Co in two steel samples taken at 687m S and 1295m NNW from the hypocenter was measured by gamma-ray spectrometry and neutron activation analysis. The results were, respectively, (2.64 +/- 0.38) x 10(1) and (3.09 +/- 0.48) x 10(-1) dpm/mg Co at the time of bombing, which are consistent with previous data by Hashizume et al. for steel rings on the surface of roofs of buildings. The present data are expected to serve as verification of the bomb neutron transport calculations. Content of nickel and copper in the samples, determined by colorimetric and neutron activation methods, respectively, was too small to account for any significant 60Co production by the (n,p) and (n, alpha) reactions. PMID- 2213690 TI - Biological and physical dosimeters for monitoring solar UV-B light. AB - A biological dosimetry system for measuring solar UV-B light was established using bacteriophage T1 with E. coli Bs-1 as the host cell. Also a new physical UV B dosimeter was developed which can specifically detect the UV spectral region related to inactivation of phage T1. Phage T1 is very stable in liquid suspension and it has adequate sensitivity to measure the intensity of solar UV-B. In addition, the survival of phage T1 responded linearly to UV fluences when plotted semi-logarithmic ally. Thus T1 seemed to have characteristic features making it suitable material as a biological dosimeter for sunlight. Outdoor experiments throughout one year showed that the mean amount of solar UV light in summer was about 6 fold larger than that in winter at Isehara (139.5 degrees E, 35.5 degrees N), Japan. A novel physical dosimeter which responds faithfully to UV-B light under atmospheric conditions on the ground was developed as well. The spectral response was very close to that of biological materials. Readings of this UV-B dosimeter could be converted into the efficiency of sunlight upon biological materials. This instrument is compact; it can also be used as an erythemal dosimeter. PMID- 2213692 TI - Gross morphological changes of the mouse brain exposed prenatally to ionizing radiation. AB - Gross morphological changes of the brains of first generation (F1) C57BL/6 x C3H hybrid male mice irradiated prenatally were studied at 6 months of age. Gravid female mice were irradiated with 1.0 Gy, 2.0 Gy or 3.0 Gy of gamma radiation on the 14th day of gestation. The brain in dorsal view was photographed. The measurements of the area and the distance of parts of the brain were made from photographs, using a computer system for biological image analysis. The body and brain weight and the area and length of the cerebral hemispheres (CHs) showed dose-related decrease. There was a dose related increase in the area of the superior colliculi (SC), the distance (DP) from the point which the medial walls of the CHs begin to slope away from the midline to the posterior end of CHs, and the proportion of the DP to the CH length. From the results of the dose-response curve, it appears that the area of the SC and the proportion of DP to CH length are affected by small doses of less than 1.0 Gy. PMID- 2213693 TI - [X-ray computed tomography of the liver with injection]. PMID- 2213694 TI - [Percutaneous angioscopy in the diagnosis of arteriopathies of the lower limbs]. AB - Because of the poor specificity of the arteriography, the authors have performed a percutaneous angioscopy before every angioplasty of the arteries of lower limbs for nearly 3 years. They define the angioscopy and describe materials and technique. The percutaneous route without surgery and without anesthesia underlines the originality of the technique. The great difficulty is to counter pulse the arterial inflow. The rate of saline irrigation and all the means of arterial blockade are described. In the second part, the "elementary images" are classified. The authors insist on the specificity of the angioscopy in the interpretation of arterial obstructions. Because of this specificity, the right treatment can be applied to any type of lesion. Angioscopy permits to foresee endoluminal surgery technique. PMID- 2213695 TI - [Anulography]. AB - Despite new imaging modalities such as MRI, the discography remains useful, particularly as the first step of chemonucleolysis. The anulography corresponds to a technical error due to the wrong position of the needle during the procedure. We have noticed 32 anulographies on 1226 discographies done in our department, between 1985 and 1989. The anulography exhibits a typical pattern that must be diagnosed; if not, that can lead to a diagnosis mistake or a wrong therapeutic attitude. The needle of discography must then be repositioned. PMID- 2213696 TI - [MRI of the normal portal system: the artefacts. Apropos of 45 cases]. AB - The protal system of 45 normal patients have been retrospectively studied on spin echo MRI sequences (interleaved cuts): multiple artifacts have been evaluated and 24% of them were visualized at the portal system level. Thus, partial volume effect responsible for almost 25% of the artifacts is not always easily seen on a single sequence. Respiratory and aortic artifacts can deteriorate the visualization of the vascular lumen but cannot be confused with a thrombosis. Well-known artifacts, as slice entry phenomenon and even echo rephasing, represent more than 60% of the artifacts: they are readily recognized when they are typical and indicate flowing blood. On the contrary, an other artifact, representing less than 5% of the total and seen at the level of the left portal vein, simulates a thrombus, on T2 weighed images. We conclude that the frequency and polymorphism of the artifacts are limiting factors of MRI value in the diagnosis of portal vein thrombosis. PMID- 2213697 TI - [Epidermoid cysts of the spleen. Report of 6 cases]. AB - The authors report 6 cases of epidermoid cysts of the spleen. They emphasize the rarity of the lesion, its pathological and clinical features, and describe the abnormalities which can be noted on plain films, ultrasonography and computed tomography. PMID- 2213698 TI - [Idiopathic achalasia of the esophagus in children. Report of 8 cases]. AB - Achalasia of the esophagus is rare in children. The authors report eight cases and emphasize two atypical clinical records: The first one is a 3 month-old infant with respiratory distress and "near miss" Sudden Death Infant Syndrome. The second one is a ten year-old boy with association of achalasia of the esophagus, ACTH insensibility and alacryma. Theses cases are discussed. PMID- 2213699 TI - [Comparative study of MRI and x-ray computed tomography in the preoperative evaluation of rectal carcinoma]. AB - Twenty-one patients with middle and low rectal carcinomas have been operated by abdominoperineal resection (APR) in 11 patients, and low anterior resection (LAR) with coloanal anastomosis in 7 and colorectal anastomosis in 3. The distance of the lower margin of the tumor to insertion of the levator ani on the rectal wall was correctly evaluated by CT in 15 of 21 cases (71%) and by MR in 14 of 21 (67%) while digital examination correctly assessed the distance in 17 of 21 (81%). CT and MR were unable to assess extension through the rectal wall. No significant discordance was observed between CT and MR in assessing extension to the perivesical fat, adjacent organs, pelvic side wall or lymphnodes. According to the TNM classification, MR correctly staged 76% (16 of 21) of patients while CT correctly staged 71% (15 of 21). PMID- 2213701 TI - [Bilateral encasement of the internal saphenous vein in a patient with lymphoma]. AB - Sonographic findings in a case of bilateral, almost symmetrical encasement of the terminal segment of the great saphenous vein by superficial sub-inguinal lymphomatous masses are presented. Duplex and color Doppler sonography also demonstrated abnormal Doppler signals within the mass. When peripheral, coalescent nodal masses are detected surrounding intact normal vessels, malignant lymphoma should be suspected. PMID- 2213700 TI - [Echographic diagnosis of peritoneal metastases in patients with ascites]. AB - A prospective study of 14 malignant ascites examined with high frequency ultrasonic probes enabled he authors to achieve a diagnosis of peritoneal metastases in 78% of cases. Peritoneal metastases appear as areas of peritoneal thickening or scalloping, as nodules, with sometimes a strong bulging, and as intestinal masses. Soft part ultrasound should be employed systematically in the diagnosis and follow up of malignant ascites. PMID- 2213702 TI - [Sub-callus epidermoid cyst. A case report]. AB - The cranio-encephalic epidermoid cysts are rare tumors. These lesions are extra axial and can occur at the infratentorial or supratentorial level. The epidermoid cysts are classically in contact with the base of the skull, and less often intraventricular; the other locations are exceptional. Because of their CT aspect (hypodense lesion, rarely isodense, well defined, without contrast enhancement, and without surrounding edema) and MR aspect (in more than 70% of the cases: more or less homogeneous lesion, hypointense in T1 and hyperintense in T2), the authors believe that it is possible to suggest such a diagnosis even with an atypically located case. We report the case of an epidermoid cyst located between the corpus callosum and the falx cerebri. PMID- 2213703 TI - Strategies for introducing foreign DNA into the germ line of fish. PMID- 2213704 TI - Insertion, expression and physiology of growth-regulating genes in ruminants. AB - Transgenic sheep with elevated concentrations of circulating growth hormone (GH) were produced by microinjecting recombinant DNA into pronuclei of zygotes. The transgenes were fusion genes of non-GH promoters with coding sequences of various growth hormone genes including human, ovine or bovine. In addition, sheep transgenic with the human growth hormone releasing factor gene were produced. Non GH promoters for fusion genes allowed novel regulation of GH production in ectopic tissues, including the kidney, liver and gut. Elevated levels of GH profoundly altered plasma IGF-1 without significantly altering rate of growth or feed efficiency. Carcass composition was altered with reduced fat. Elevated GH induced diabetes, resulting in death by 1 year of age. These studies indicate the need for improved regulation of inserted genes or investigation of alternative systems, such as GH receptors, to improve growth using the transgenic approach in ruminants. PMID- 2213705 TI - Cloning embryos by nuclear transfer. AB - Nuclear transfer has been used to study the differentiation process in embryogenesis, as well as a method to produce multiple identical individuals. When nuclei are transferred to activated, enucleated oocytes the nuclei swell in diameter, synthesize DNA, acquire cytoplasmic proteins and release nuclear proteins. This protein exchange is thought to result in specific genomic modifications resulting in the transferred nucleus behaving as a zygotic nucleus. The limitations of development observed with relatively differentiated nuclei are thought to result from asynchronies in the length of the cell cycle between the donor cell and the recipient cytoplasm, as well as insufficient genomic modifications. This results in incomplete DNA synthesis and incomplete reprogramming before the first cell division. These nuclear modifications are discussed with data from amphibians and mammals. PMID- 2213707 TI - Use and desired properties of poultry vaccines. PMID- 2213706 TI - Modification of milk composition. AB - Revolutionary new opportunities for the modification of milk composition have been created by the development of methods for gene transfer and targeted mutation of genes may extend the range of opportunities still further. Exploitation of these opportunities depends upon selection and cloning of milk protein genes and identification of the sequences that govern tissue-specific hormonally induced expression in the mammary gland. Fragments of the ovine beta lactoglobulin gene fused to cDNA for the human therapeutic proteins clotting factor IX and alpha-1 antitrypsin have directed production of these proteins in the milk of transgenic mice and sheep. Factor IX was biologically active and co migrated with authentic proteins, but was present at too low a concentration for commercial exploitation. Recent observations suggest that fusion genes containing genomic clones direct production of higher concentrations of protein. Mouse whey acidic protein genomic sequences also directed production of low concentrations of human tissue plasminogen activator in the milk of transgenic mice. Targeted expression of this kind may be used for the production of therapeutic and industrial proteins, to increase the concentration or modify the nature of milk proteins, reduce the concentration of lactose, change the composition of fat or direct production of bacteriocidal proteins in milk in order to combat mastitis. PMID- 2213708 TI - Recombinant viruses as poultry vaccines. PMID- 2213710 TI - Transmission of exogenous genes into the chicken. AB - Injection of infectious non-replicating REV vector directly beneath the chicken blastoderm leads to infection of embryonic stem cells. Vector sequences are present in a variety of specialized tissues of embryos and mature birds derived from infected blastoderms. Breeding studies show that replication-defective REV vectors can transfer heritable, non-viral genetic information into the chicken germ line. PMID- 2213709 TI - Developmental regulation and tissue-specific expression of a chimaeric phosphoenolpyruvate carboxykinase/bovine growth hormone gene in transgenic animals. AB - Expression of the bovine growth hormone (bGH) gene, directed by the phosphoenolpyruvate carboxykinase (PEPCK) gene promoter, in transgenic animals was investigated. Different lengths of the 5' PEPCK promoter-regulatory domain were utilized to control bGH expression; these included -2000/+73, -460/+73, 355/+73, and -174/+73. The chimaeric PEPCK/bGH gene containing -460/+73 of PEPCK 5' flanking sequence (PEPCK/bGH(460] is regulated by cAMP, insulin, and dexamethasone in the same manner as the endogenous PEPCK gene. This PEPCK promoter-regulatory domain also controls the tissue-specific expression of the bGH gene to liver, kidney, adipose tissue, jejunum and mammary gland. Furthermore, the correct developmental pattern of expression is observed in the mouse lines which contain PEPCK/bGH(460). The transgene mRNA is not detected during fetal development until Day 19. At Day 1 after birth, due to alterations in the insulin:glucagon ratio, the amounts of transgene mRNA are greatly increased, similar to the endogenous PEPCK gene. PMID- 2213711 TI - Animal production industry in the year 2000 A.D. AB - One can easily envision that, in the very near future, all bulls being progeny tested will be screened for genomic markers linked to economic traits and females may also be screened if enrolled as donors in a nuclear transfer programme. The concept of producing large numbers of genetically identical embryos, frozen, sexed, screened for economic traits and produced inexpensively from slaughterhouse by-products, is within our grasp. While large scale commercialization of these concepts is a function of time, knowledge and cost effective biotechnologies, all of these concepts have already been demonstrated. The production of transgenic animals and embryos will be accelerated as gene mapping links genes to economic traits. What will happen to protein production when commercial cow herds can be made up of one or more female clone lines mated to bulls of the same clone? The obvious answer is predictability of performance to a magnitude never before achieved in agriculture. PMID- 2213712 TI - In-vitro mutagenesis of the bovine growth hormone gene. AB - The biological activities of bovine growth hormone (bGH) were studied in a transgenic mouse model system. The following experimental design was used: (1) in vitro mutagenesis of the bGH gene; (2) expression of the mutated gene in cultured mouse cells under transcriptional regulation of the mouse metallothionein I promoter; (3) binding studies of the mutated and wild-type protein to mouse liver membrane preparations; (4) generation of transgenic mice which express the mutant hormone; and (5) growth rate analysis of transgenic mice. Removal of the alanine +1 codon from the bGH gene or a substitution of serine for cysteine 189 does not affect the ability of the mutant protein to influence transgenic mouse growth. Also, mutations which increase the hydrophobicity within the bGH alpha helix 3 region (amino acid residues 109-126) do not alter the enhanced growth rate in transgenic mice which express these mutated bGH proteins. PMID- 2213713 TI - New animal breeding techniques and their application. AB - The new biotechnologies of gene transfer, in-vitro production, cloning and sexing of embryos have been developed and are being refined with efficiencies suitable for use in animal agriculture. Efficient in-vitro systems for maturing oocytes and capacitating spermatozoa, for fertilizing and developing the embryos have resulted in commercial in-vitro production of embryos. Cloning of embryos by nuclear transfer has been accomplished for sheep, cattle, pigs and rabbits with nuclear material supplied by embryos as late as the 120-cell stage in sheep. Embryos have been recloned but much research is needed to increase the efficiency of this procedure. Research is needed to develop the use of cultured cells in embryo cloning so that the number of clones may be increased to thousands or millions. Embryos of most species can be sexed in a non-damaging way with male specific antibodies and a more efficient method, amplified DNA hybridization, is beginning to be tested commercially. Transgenic embryos or offspring have been produced for mice, rats, rabbits, chickens, fish, sheep, pigs and cattle. Genes can be targeted for expression in specific tissues but more efficient methods and a better understanding of the genes to be transferred as well as control by man of the time and tissue of specific gene expression are needed. Before many transgenic animals of value can be made, we must know which genes to introduce. Presently there is a poor understanding of the genes influencing animal growth, efficiency of growth, environmental adaptation, meat, milk or egg composition or animal disease resistance. Their identification will come from badly needed efforts to map the genome of domestic animals. These and other new technologies promise to change livestock breeding drastically in the next decade. PMID- 2213714 TI - Vectors and genes for improvement of animal strains. AB - Strain improvement of agriculturally important animals will require efficient techniques for gene delivery, the ability to regulate the expression of the newly introduced genes and, most important, the identification of genes whose appropriate expression could cause improvement of the animal. We have developed a series of avian retroviral vectors that can be used to introduce new genetic information into the germ line of chickens, for which transgenics cannot be created by direct microinjection of DNA into fertilized eggs. We have identified a 220-bp segment of the chicken skeletal muscle alpha-actin gene that can cause other genes to be expressed specifically in striated muscle. This chicken promoter shows correct tissue specificity in transgenic mice and presumably could be used in other mammalian species. The skeletal muscle alpha-actin promoter has been inserted into the avian retroviral vectors and the promoter is functional in cultured cells infected by these retroviral vectors. The tissue specificity of the expression of the skeletal muscle alpha-actin promoter carried by the retroviral vectors will soon be tested in vivo. We are studying two types of genes that might be useful in strain improvement; genes that could produce dominant resistance to infection by pathogenic viruses, and genes that could play critical roles in muscle development. Expression of the envelope glycoprotein of retroviruses can specifically block the cellular receptor that viruses use to infect a susceptible cell. Expression of the avian leukosis virus subgroup A envelope in transgenic chickens prevents infection by pathogenic viruses of the same subgroup. We are attempting to block reticuloendotheliosis virus infection by expressing the reticuloendotheliosis envelope glycoprotein. We have shown that we can block infection in cultured cells, and we are now creating retroviral vectors for experiments in vivo. We have also begun to study the cellular homologue of the ski oncogene, which has been shown to stimulate the differentiation of quail myoblasts in vitro. Biologically active cDNAs have been isolated; we have now begun to analyse the effects of expressing the c-ski proteins in the whole animal. PMID- 2213715 TI - Maintenance and differentiation in culture of pluripotential embryonic cell lines from pig blastocysts. AB - Cell lines were established from explanted blastocysts of domestic pigs; the cells could be maintained indefinitely when grown on mouse fibroblast feeder cell layers. They differentiate spontaneously at high densities, or when allowed to form aggregates when cultured on a non-adhesive substratum. Their appearance and differentiative behaviour resembles that of mouse embryonic stem cell lines. We are currently attempting to establish whether these cultures represent primary ectodermal lineages which would be of particular relevance to developmental and transgenic studies. PMID- 2213716 TI - Regulation of expression of a class I major histocompatibility complex transgene. PMID- 2213717 TI - Interferons at the placental interface. AB - The antiluteolytic factors secreted by sheep and cattle conceptuses are closely related structurally to alpha-interferons (IFN-alpha s). They are known as ovine and bovine trophoblast protein-1 (oTP-1 and bTP-1), respectively. The mRNAs for oTP-1 and bTP-1 are transcribed from multiple genes and are the major translatable messages of Day 13-17 sheep conceptuses and Day 15-20 cattle conceptuses. The proteins belong to the 172-amino acid IFN-alpha II (or IFN omega) subfamily and have the typical antiviral and antiproliferative properties of the 166-residue IFN-alpha Is. These embryonic interferons also bind to the IFN alpha receptor, which is present in uterine endometrium in high concentrations, and can influence the production of prostaglandin F-2 alpha and the pattern of protein secretion in that tissue. Through use of in-situ hybridization procedures on tissue sections and Northern and dot blot analyses of extracted conceptus RNA, ovine oTP-1 mRNA has been shown to increase markedly around Day 13 and to decrease after about Day 15 of pregnancy. The mRNA is confined entirely to cells of the trophectoderm. Significant induction of mRNA that hybridizes to an oTP-1 cDNA occurs in response to exposure to polyI:polyC in Day 11 sheep blastocysts which normally have low levels of oTP-1 expression. However, the basis for induction in the normal progression of embryonic development remains unclear. The fact that preimplantation conceptuses of other species, e.g. pig, release substances with antiviral activity suggests that IFNs may have an important role in pregnancy that extends beyond the domestic ruminants. PMID- 2213718 TI - Integration, expression and germ-line transmission of growth-related genes in pigs. AB - We have produced transgenic pigs that harbour structural genes for bovine and human growth hormone (bGH and hGH) ligated to a mouse metallothionein-I (MT) promoter, human growth hormone-releasing factor (hGRF) ligated to the MT or mouse albumin (ALB) promoter, and human insulin-like growth factor-I (hIGF-I) ligated to MT promoter. From 0.31 to 1.03% of microinjected ova developed into transgenic pigs with the various fusion genes. Foreign GH was present in plasma of 61% of the MT-hGH and 89% of the MT-bGH transgenic pigs. Two of 7 pigs with MT-hGRF and all 3 ALB-hGRF transgenic pigs had high concentrations of GRF in their plasma, but plasma concentrations of porcine GH (pGH) were not higher in GRF transgenic pigs than in littermate control pigs. In contrast, plasma concentrations at birth ranged from 3 to 949 ng hGH/ml for MT-hGH transgenic pigs and 5 to 944 ng bGH/ml for MT-bGH transgenic pigs. Presence of the foreign GH depressed endogenous pGH to non-detectable levels. In MT-bGH transgenic pigs, plasma IGF-I was elevated more than 2-fold, plasma glucose was elevated about 30 mg/dl, and plasma insulin was 20-fold higher than in littermate or sibling control pigs. Two lines of pigs expressing the MT-bGH transgene gained 11.1% and 13.7% faster, and were 18% more efficient in converting feed to body weight gain than were sibling control pigs. Expression of the MT-bGH transgene caused a marked repartitioning of nutrients from subcutaneous fat into other carcass components, including muscle, skin, bone and certain organs. The persistent excess hGH or bGH in transgenic pigs was detrimental to general health; lameness, lethargy and gastric ulcers were the most prevalent problems. Gilts that expressed the hGH or bGH transgenes were anoestrous. Germ-line transmission was obtained in 4 of 5 expressing transgenic boars and 4 of 5 nonexpressing transgenic boars and gilts. From 2% to 73% of progeny inherited a transgene from founder transgenics. All transgenic progeny of MT-hGH, MT-bGH and MT-hGRF founder males expressed the transgene if their sire also expressed the gene. The concentration of bGH or hGH in plasma of transgenic progeny was similar to the concentration present in the founder transgenic. PMID- 2213719 TI - Production of transgenic pigs harbouring a rat phosphoenolpyruvate carboxykinase bovine growth hormone fusion gene. AB - Over the past 5 years, reports detailing the production of transgenic pigs have focussed on enhanced growth performance. Phenotypic side-effects observed in pigs harbouring chimaeric constructs containing metallothionein or Moloney murine leukaemia virus transcriptional activators fused to growth hormone (GH) structural genes have been attributed to chronic overexpression of GH. In an effort to regulate a transgene product more effectively, a liver specific 460 bp 5' flanking sequence of the rat phosphoenolpyruvate carboxykinase (PEPCK) gene was ligated to a BamHI site of the first exon of the genomic bovine GH (bGH) structural gene. Following micro-injection of the PEPCK/bGH construct into 1- and 2-cell pig zygotes. 124 offspring were produced of which 7 pigs were determined to be transgenic by dot-blot and Southern analysis. The PEPCK gene expression, in terms of tissue and developmental specificity, appears similar to that observed in PEPCK/bGH transgenic mice. Germ-line transmission was identified in 1 of 3 mated founders. Dramatic influences on backfat thickness were observed including a 41% reduction in backfat depth when compared to non-transgenic sex-matched littermate control pigs. Both the regulation and characterization of gene expression in PEPCK/bGH transgenic pigs are under investigation. PMID- 2213720 TI - Electrophoretic map of acidic and neutral human spermatozoal proteins. AB - A high resolution two dimensional electrophoretic technique (2-D), isoelectric focusing followed by polyacrylamide gel electrophoresis, for separation of neutral and acidic human spermatozoal proteins was established. Silver stained 2 D gels revealed over 260 proteins with Mr 20-200 kDa and pI between 4.5 and 7.8. Membrane proteins were radio-iodinated in their hydrophobic cores with the hydrophobic photoactivatable reagent 3 (trifluoromethyl)-3-(m-[125I]iodophenyl) diazirine (TID). Externally exposed carbohydrate side chains were radiolabelled by NaB(3H)4 reduction. 2-D lectin blotting was performed with horseradish peroxidase conjugated Concanavalin A (Con A), biotinylated Vicia faba agglutinin (VFA) and Solanum tuberosum agglutinin (STA). A map of 258 human spermatozoal proteins is presented and 48 TID-labelled proteins have been biochemically characterized. PMID- 2213721 TI - The humoral autoimmune response to vasectomy described by immunoblotting from two dimensional gels and demonstration of a human spermatozoal antigen immunochemically crossreactive with the D2 adhesion molecule. AB - The specificity of human serum antispermatozoal antibodies was analysed by immunoblotting after two-dimensional electrophoretic separation (IEF/PAGE) of human spermatozoal proteins. Spermatozoal proteins with Mr 20-200 kDa and pI between 4.5 and 7.8 were analysed for antigenicity. Fifteen sera (four female and 11 male) were analysed for antisperm IgG antibodies. Individual IgG binding patterns were observed. The antisperm antibody response to ligation of the vas deferens was described by immunoblotting analysis of sera taken pre- and post operatively at regular intervals from three men undergoing vasectomy. The high resolution of spermatozoal antigens allowed a specific description of the humoral response to vasectomy. Both appearance and disappearance of spots were observed in the postoperative period, indicating induction of new antibody producing clones and binding of former free antibodies in circulating immunocomplexes. In one patient five glycosylated proteins induced an IgM response 2 weeks after vasectomy. Four of these autoantigens with Mr of 122 kDa, 119 kDa, 104 kDa and 77 kDa and pI of 5.9, 6.1, 7.7 and 6.0, respectively, have previously been shown to be intrinsic membrane proteins (Naaby-Hansen, (1990) J., Reprod. Immunol. 17). An observed immunochemical crossreactivity between the interneuronal adhesion molecule, D2-protein and an antigen extracted from human sperm and teratomas is discussed. PMID- 2213722 TI - The effect of adjuvants on antibody titers in mouse vaginal fluid after intravaginal immunization. AB - Intravaginal (ivag) immunization elicits secretory immune responses in the female reproductive tract, but little is known about the safety and effectiveness of adjuvants for such immunization. Mice were immunized intravaginally once daily for 5 days with large doses of horse ferritin combined with aluminum hydroxide (AH), muramyl dipeptide (MDP), monophosphoryl lipid A (MPL), dimethyl dioctadecyl ammonium bromide (DDA) or cholera toxin (CT). Titers of anti-ferritin IgA and IgG were measured in vaginal fluid by ELISA. The most effective adjuvant for ivag primary immunization was AH, while MPL was most effective for ivag boosting. None of the adjuvants caused a detectable tissue reaction in vaginal mucosa. Primary ivag immunization for 5 days with ferritin and AH followed by ivag boosting for 5 days with ferritin and MPL elicited higher IgA titers in vaginal fluid than systemic priming and boosting with ferritin and AH or systemic priming and ivag boosting with ferritin and MPL. Systemically immunized animals exhibited the highest IgG titers in vaginal fluid. The data indicate that adjuvants, particularly AH, can increase local immune responses to intravaginal immunization, but it should be noted that multiple applications of large doses of antigen were used and that this route of sensitization may be relatively inefficient. PMID- 2213723 TI - Decidua-associated suppressor activity and viability of individual implantation sites of allopregnant C3H mice. AB - Release of soluble suppressor activity from individual implant site decidua of DBA/2-mated C3H/HeJ mice was measured on days 12.5-13.5 of pregnancy. Suppressor activity varied among sites and followed a distribution curve that was displaced towards low suppression when resorption sites were compared to healthy embryonic implants. Pre-immunization against the DBA/2 strain paternal antigens failed to increase resorption (by loss of low suppression implants) but led instead to a reduced resorption rate. This was associated with an increase in soluble suppressor activity obtained from decidua. Some reduction in resorption occurred independent of an increase in the level of suppression suggesting additional contributing factors to the immunization effect. PMID- 2213724 TI - Immunological detection of cat uterine proteins in ferrets, dogs and baboons. AB - In the cat, a high molecular weight (greater than 320 kDa) estrogen (E2) dependent protein (CUPED) and a group of low molecular weight (28 kDa, 36 kDa, 41 kDa) progesterone (P)-dependent proteins (PDP) are synthesized by the epithelial cells of the deep uterine glands and secreted into the lumen. The present study was designed to investigate the possibility that other species synthesize proteins similar to CUPED and PDP in response to steroids. Uterine flushings and media from cultured endometrial explants obtained from E2 or P dominated animals were analyzed on Western blots for the presence of proteins which cross-react with antibodies raised against CUPED and PDP. CUPED antibody immunoreacted with a protein band at approximately the same molecular weight as CUPED in the media and flushings from E2-treated ferret, dog and baboon, but not from rat, mouse or hamster. In the cat, ferret and dog, specific immunocytochemical staining was observed in the apical portion of the secretory cells. In the baboon, staining was observed in both the basal and apical areas of the epithelial cells. The presence of CUPED in the uterine lumen during the E2-dominated phase of the reproductive cycle in several species suggests that CUPED may play a general role in providing the necessary biochemical milieu for reproductive success. The PDP antibody did not cross-react with proteins in the media of species other than cat, and therefore may be unique to the cat. PMID- 2213725 TI - A monoclonal antibody, 4H12, recognizes a surface antigen found on granulated metrial gland cells in the murine decidua. AB - A monoclonal antibody (MAb), designated 4H12, was selected for reactivity to a surface antigen on PYS-2 teratocarcinoma cells. 4H12 was the product of a fusion of lymphoid cells of a non-immunized pregnant C57BL/6 mouse to NS-1 myeloma cells. Initial studies utilizing immunohistochemistry revealed that MAb 4H12 bound to an antigen found on cells in the decidua basalis of 7-, 8- and 10-day pregnant mice. Antigen-positive cells of 11--19-day pregnant mice were also found predominantly in the decidua. A few antigen-positive cells were found in the labyrinth of the placenta and up against Reichert's membrane. Antigen-positive cells were morphologically and spatially distinct, oval to round with large periodic acid Schiff positive granules. Indirect immunofluorescent (IIF) labeling of decidual cultures showed antigen on the surface of cells that were small, oval to round and adherent. The antigen recognized by MAb 4H12 was removed from tissue sections with trypsin and protease and therefore is suggested to be a protein. We conclude that MAb 4H12 recognizes a surface antigen found on cells historically described as granulated metrial gland (GMG) cells. This MAb should greatly facilitate the further analysis of the life history and function of GMG cells during pregnancy. PMID- 2213726 TI - Immune privilege in the testis. PMID- 2213727 TI - The testis and tissue transplantation: historical aspects. AB - Transplantation experiments involving the testis have been performed since the days of John Hunter, who transplanted a testis into the belly of a hen. The first person to use the testis as a site of transplantation appears to have been Sand, who found in 1919 that an ovary transplanted into the substance of the testis developed follicles. By 1970, there was considerable evidence that the testis under some circumstances was a relatively favorable site for graft survival. However, much of the evidence was equivocal, and the immunological privilege was by no means complete. PMID- 2213728 TI - Immunocompetence of inflammatory cells in rabbit testes infected with Treponema pallidum. AB - Systematic studies were conducted in rabbits to delineate factors favoring the predilection for multiplication of T. pallidum in testes. The results strongly suggest that, in addition to the mucoid material produced during lesion development regardless of the site of infection, a whole array of testicular substances with immunomodulatory activity may largely contribute to the propagation and delayed clearance of the pathogen from the testicular environment and most likely from the host. PMID- 2213729 TI - Testicular relapse of acute lymphoblastic leukemia (ALL). AB - Several aspects of acute lymphoblastic leukemia (ALL) converge towards the testis: (1) the overall prognosis is worse for boys than for girls; (2) the testis is a more frequent site of relapse of ALL than other organs; (3) age over 10 years (coinciding with the start of pubertal activation) is a recognized "high risk" background factor; (4) occult testicular relapse of ALL seems to be common. The underlying mechanisms behind these observations are discussed. If immunological defence mechanisms are important for the rejection of ALL cells from the body, the immunological tolerance of the testicular microenvironment might favour growth of ALL cells. Alternatively, the presence of specific growth promoting factors in the testis might enhance tumour cell proliferation. In this context, the newly discovered presence of a lymphocyte growth factor (interleukin 1-like, IL-1) at high concentrations in the testis of several mammals, including man, is of great interest. As this factor seems to be under hormonal control, in future it may offer opportunities to influence the tendency to testicular involvement, and thus prognosis, in ALL. PMID- 2213730 TI - Testis physiology relevant to immunoregulation. AB - Intra-testicular transplants are placed in rodents into the large lymphatic sinusoids of the interstitial tissue of the testis. These sinusoids are filled with a protein-rich extracellular fluid that supplies all the requirements of the grafts until vascularization takes place. The testicular microvascular endothelium regulates transport of T lymphocytes and immunoglobulin G to the testis and may thus contribute to regulation of the immune system in this organ. Differences in the organization of the lymphatic drainage exist between species, but in every studied species lymphatic drainage from the testis leads to lymph nodes. PMID- 2213732 TI - Activation of the immune system in the testis. AB - The present concept for the mechanism of prolonged transplant survival in the testis suggests that lymphocyte activation is inhibited locally in this site by testicular products. As the testis produces several immunoregulatory factors, the behaviour of lymphocytes in the testis may depend on the net effect of all these factors on intralymphocytic events. In the present article, the extra- and intracellular events associated with lymphocyte activation are reviewed and the steps of lymphocyte activation which might be subject to interference by testicular factors are identified. PMID- 2213731 TI - Regulation of the testis. AB - The testicular cells are regulated by factors produced locally in the testis. These factors include peptide growth factors, pro-opiomelanocortin derivatives, neuropeptides and steroids. Several agents able to affect steroido- and spermatogenesis can also affect leukocytes and many of the testis-regulating factors are produced by immune cells, suggesting that testicular cells and leukocytes may interact. In the present article, the effects of various testicular cell and leukocyte produced factors on steroido- and spermatogenesis are reviewed. The possibility that leukocytes may produce substances able to affect the testicular functions suggests that inhibition of immune system activation in the testis may be important also for reasons other than protection of autoantigenic germ cells from an autoimmune attack. PMID- 2213734 TI - Recent evidence for immune privilege in the testis. AB - In the last 20 years, it has been shown that while first-set intra-testicular grafts rarely induce systemic immunity, second-set intra-testicular grafts are usually rejected, if a pre-existing immunity has been generated by first-set skin grafts. These observations suggest that while the efferent limb of the pre sensitized immune response is operative in the testis, the immune system can not be activated against antigens present only in this site. Various theories have been advanced to explain this phenomenon. The most likely explanation at present seems to be that the testis contains specific immunosuppressive factors that inhibit lymphocyte activation in this site. PMID- 2213733 TI - Role of testicular autoantigens and influence of lymphokines in testicular autoimmune disease. AB - The present data on testicular autoimmune disease suggest that CD4+ helper type T cells are responsible for adoptive transfer of murine experimental autoimmune orchitis (EAO). In passive EAO, the earliest lymphoid cell infiltration is confined to terminal segments of seminiferous tubules. Both orchitis and vasitis develop. In active EAO, any location in the testis is affected, frequently involving subcapsular seminiferous tubules. The location of maximum histopathology in passive EAO coincides with the site in the normal testis that expresses maximal Ia. Demonstration of IgG in the testis after immunization with testicular antigens or after transfer of sera from orchiectomized mice immunized with testis shows that autoantigens are present on the germ cells outside the Sertoli cell barrier, suggesting the existence of dynamic protective mechanisms against immune responses to the non-sequestered autoimmunogenic germ cells in normal individuals. PMID- 2213735 TI - Problems in the clinical diagnosis of stress incontinence. AB - A significant number of women suffer from urinary incontinence, which often requires surgical intervention. Prior to proceeding with surgery, it is essential that all women undergo a thorough preoperative assessment to detect nonsurgical causes of their urinary leakage. This paper reviews the reliability of the initial history and basic clinical tests in the evaluation of women with lower urinary tract abnormalities. PMID- 2213736 TI - Nonsurgical treatment of detrusor overactivity in postmenopausal women. AB - Detrusor overactivity with subsequent urge incontinence becomes increasingly more prevalent as women age. Because of that, most women treated for detrusor instability and hyperreflexia are postmenopausal and are not always good candidates for the same treatments given to their younger counterparts. Nonsurgical treatments of detrusor overactivity are available to postmenopausal women. PMID- 2213737 TI - Histology of the connection between the vagina and levator ani muscles. Implications for urinary tract function. AB - The proximal urethra is a mobile structure, and voluntary control of its position is an integral part of the initiation of urination and continence. This paper describes the histology of the vagina's attachment to the medial portion of the levator ani muscles, which, because of the intimate attachment of the vagina and urethra, is responsible, in part, for control of the urethral position. A histologic examination of 1,500 serial microscopic slides from eight women, dissection of four bodies and study of whole pelvis cross-sections from two cadavers were performed. Smooth muscle, collagen and elastin fibers of the vaginal wall and paraurethral tissues directly interdigitate with the muscle fibers of the most medial portion of the levator ani, in the region of the proximal urethra. This strong connection lies at a level just below the entry of the urethra into the bladder and extends downward to the level of the perineal membrane (urogenital diaphragm) in an area corresponding to the mobile portion of the urethra. The inseparable nature of the vagina and urethra in this region makes it possible for the connection of the levator ani to the vagina to control the proximal urethral position. These observations suggest a specific role of the medial levator ani muscle in controlling vesical neck position and open the question of the specific part played by this arrangement in voiding and continence relative to other factors known to influence lower urinary tract function. PMID- 2213738 TI - Predictive value of urethroscopy as compared to urodynamics in the diagnosis of genuine stress incontinence. AB - A retrospective chart review was undertaken of 204 patients who underwent dynamic urethroscopy. Ninety-nine patients with a diagnosis of genuine stress incontinence were evaluated urodynamically and urethroscopically to determine the predictive accuracy of the sensitivity and specificity of each of these diagnostic modalities. The urodynamic cough profile was both highly reactive and specific for genuine stress incontinence, with sensitivity and specificity of 95% and 100%, respectively, whereas dynamic urethroscopy yielded sensitivity and specificity of 60.2% and 79.1%, respectively. Dynamic urethroscopy is a relatively insensitive predictor of genuine stress incontinence, with many equivocal findings (11%) as well. The urodynamic cough urethral pressure profile is recommended for diagnosing this condition. PMID- 2213739 TI - Urethral mobility and its relationship to stress incontinence in women. AB - Multiple physiologic factors, only one of which is urethral support, make up the female continence mechanism. Abnormal urethral support leads to deficient transmission of abdominal pressure to the urethra, which results in genuine stress incontinence in some women. Many techniques are available for measuring urethral mobility. The determination of urethral mobility is not useful in the diagnosis of urinary incontinence. However, it provides some information about which surgical procedure is most appropriate for the correction of genuine stress incontinence. PMID- 2213740 TI - Urinary tract infection in women. Current role of single-dose therapy. AB - Administration of a single dose of an antimicrobial agent is acceptable therapy for women with uncomplicated lower urinary tract infections. There is adequate information in the literature to support the clinical use of single-dose therapy, although there is still a need for further, well-designed, sufficiently large studies that compare single-dose therapy to abbreviated-course (3-day) and traditional (7- to 14-day) therapy. PMID- 2213741 TI - Genital prolapse with and without urinary incontinence. AB - Procidentia, vaginal vault prolapse and severe cystocele may be associated with potential urinary incontinence, which becomes overt only after surgical repair of the genital prolapse. The normal support of the pelvic organs is provided by the pelvic diaphragm (levator ani and coccygeus muscles). The levator plate is a firm, muscular plate between the coccyx and anus formed by fusion of the levator ani muscles on each side. Recent investigators have indicated that the main mechanism for weakening the pelvic muscles occurs as a result of childbearing, when stretch injury of the pudendal nerve causes denervation of the muscles. This injury is aggravated with the changes of aging and has effects on anogenital prolapse and stress incontinence. There may be iatrogenic causes of both prolapse and stress incontinence when an operation produces a change in the direction of tissue forces or removes a prior barrier to incontinence. The evaluation of patients must include the actual and potential aspects of genital prolapse and incontinence. Testing for stress incontinence must be performed before and after reduction of the genital prolapse. Surgical repair should be planned carefully to correct all the significant and potential defects in the urogenital tract. Ideally a normal vaginal axis with adequate length will be restored, and urinary function will not be compromised. PMID- 2213742 TI - Importance of a neurologic evaluation in women with lower urinary tract dysfunction. AB - The normal coordinated functions of the bladder and urethra are controlled by a set of central and peripheral reflex mechanisms. Disruptions of these neuronal reflexes may produce abnormalities in the storage and expulsion of urine. Electrophysiologic testing can be employed to complement other urodynamic tests used in the evaluation of these patients and also to document that abnormalities previously thought to be anatomic in origin in reality may be secondary to neurologic dysfunction. PMID- 2213743 TI - A practical approach to the painful bladder syndrome. AB - The painful bladder syndrome (PBS) is a progressive and painful disease of the bladder that may lead to fibrosis, contracture and reduction of bladder capacity. The usual symptoms are urinary urgency, frequency, nocturia, chronic pelvic pain and lower abdominal pain upon filling of the bladder. A retrospective analysis was performed on 21 women with PBS between March 1987 and March 1988. The patients were treated weekly with a bladder pillar block, bladder distention and dimethyl sulfoxide instillation. Symptomatic relief was observed in 80% of the patients so treated. The maximum bladder volume increased from 185 to 475 mL (P less than .01). The side effects were minimal. PMID- 2213745 TI - Computed tomographic and ultrasonographic findings in women with acute fatty liver of pregnancy. AB - Acute fatty liver of pregnancy is associated with complications that can influence antepartum management and necessitate delivery. To date, liver biopsy has been regarded as the "gold standard" for diagnosis. Radiologic evaluation of the liver has been suggested as a less invasive means of diagnosing this entity. Five patients with acute fatty liver of pregnancy underwent ultrasonography; three underwent concomitant computed tomography (CT) of the liver. The liver appeared to be normal in all the patients undergoing CT evaluation and all undergoing ultrasonography except one. Normal liver examinations are not unusual findings in patients with acute fatty liver of pregnancy. PMID- 2213744 TI - Stripping the fetal membranes at term. Is the procedure safe and efficacious? AB - A prospective, randomized investigation was undertaken in a low-risk group of pregnant women at term (38-42 weeks' gestation) to determine if stripping the fetal membranes would safely result in earlier delivery. Ninety-nine patients entered the study; 51 underwent stripping of the membranes, and 48 controls did not. Fifty-nine percent of the patients in the stripped group delivered within one week as compared to 21% in the nonstripped group (P less than .0003). Two pregnancies in the stripped group advanced beyond 42 weeks' gestation as compared to six pregnancies in the control group (P = .12). A single gravida in the control group developed chorioamnionitis during labor. There were no other infections or other complications. Stripping the membranes was associated with earlier delivery and was not associated with any complications. PMID- 2213746 TI - Mayer-Rokitansky-Kuster-Hauser syndrome with splenosis. A case report. AB - This is the first reported case of simultaneously occurring pelvic splenosis and Mayer-Rokitansky-Kuster-Hauser syndrome. No other congenital or anatomic abnormalities were observed in the patient, and she had no history of abdominal trauma or surgery. Endometriosis was suspected initially during laparoscopy for pelvic pain. After tissue removal at laparotomy, the histologic evaluation established the diagnosis of splenosis. Biopsy at laparoscopy should be considered to confirm the diagnosis in the presence of a congenital anomaly and lesions suspected of being endometriotic. PMID- 2213747 TI - Coexistence of an intrauterine pregnancy with both an ectopic pregnancy and salpingitis in the right fallopian tube. A case report. AB - The current epidemic of pelvic inflammatory disease and recent advances in gynecologic techniques have resulted in a marked increase in the incidence of combined pregnancy. In the case reported on here the coexistence of an intrauterine pregnancy with acute salpingitis and an ectopic gestation in the same fallopian tube led to early diagnostic errors. PMID- 2213748 TI - Ruptured mature cystic teratoma of the ovary with recurrence in the liver and colon 17 years later. A case report. AB - A mature cystic teratoma of the ovary occurred in a 51-year-old woman and recurred as a large intrahepatic tumor mass as well as a small mass in the transverse colon 17 years after rupture, intraperitoneal spillage of tumor contents and subtotal surgical removal of the ovarian lesion and peritoneal implants. The patient was treated with a partial hepatectomy and a segmental transverse colectomy. The recurrent lesions, which contained histologically fully mature teratomatous elements only, were excised; the result was a complete cure. To our knowledge this is the first documented report on such a complication of mature cystic teratoma of the ovary. PMID- 2213749 TI - Conservative therapy for adnexal torsion. A case report. AB - Adnexal torsion has traditionally been treated with oophorectomy because of the fear that untwisting the ovarian pedicle may result in a thrombotic embolus. Such a patient had bilateral adnexal torsion secondary to dermoid cysts. Since standard therapy, oophorectomy, was performed, the patient was surgically castrated. A review of the literature revealed no reported cases of a thrombotic embolus arising from the untwisting of twisted adnexa and supported conservation of the adnexa rather than routine extirpation, except when necrotic. PMID- 2213750 TI - Remodelling the pyramid--a pediatric prospective. PMID- 2213751 TI - The clinical significance of immune reactions with some streptococcal antigens in rheumatoid arthritis. AB - The level of antibodies and delayed-type hypersensitivity to the group specific polysaccharides and cell wall proteins of groups A, B, C and G streptococci was determined in 247 patients with rheumatoid arthritis (RA) as well as in healthy persons and in patients with other articular disorders by means of an enzyme linked immunosorbent assay, passive hemaglutination and leukocyte migration inhibition tests. An increase of the immune response to antigens of group B streptococcus was found in patients with RA. The greatest sensitization against these antigens was typical for high disease activity of short duration, and a rapidly progressive course of RA. High titers of antibodies to polysaccharide of group B streptococcus appeared in the synovial fluid in the early stages of the clinical development of RA. Values of immune response to streptococcal antigens correlated well with the titer of rheumatoid factor and the concentration of immunoglobulins and immune complexes. The presence of group B streptococcus in the urogenital tract appeared more often in patients with RA than in healthy persons. The possibility of a triggering role for immune reactions with antigens of group B streptococcus in the immunopathological process of RA is discussed, as well as the diagnostic significance of our results. PMID- 2213753 TI - Suppressed serum erythropoietin response to anemia and the efficacy of recombinant erythropoietin in the anemia of rheumatoid arthritis. AB - Serum erythropoietin (EPO) was measured by radioimmunoassay in 67 patients with rheumatoid arthritis (RA). Twenty of these patients judged to have iron deficiency anemia, based on reduced serum ferritin levels, had higher serum EPO levels than did the 24 other anemic patients with normal or elevated serum ferritin levels. A significant negative correlation between serum EPO and hemoglobin concentrations was noted in the former group, but not in the latter. Human recombinant erythropoietin (r-EPO) was administered to 6 anemic patients with RA, resulting in improvement of anemia in 4 patients, 2 of whom showed no change in RA activity. These findings suggest a suppressed serum EPO response ot anemia and the effectiveness of r-EPO in treating anemia associated with RA. PMID- 2213752 TI - Antibodies to denatured type II collagen in rheumatoid arthritis: negative association with IgM rheumatoid factor. AB - Serum samples from 129 patients with definite or classic rheumatoid arthritis (RA) were assayed by ELISA for antibodies to denatured bovine type II collagen (dII). All patients had active disease at the time of serum sampling. Anti-dII antibodies were found in 18 (14%) of 129 patients (95% confidence intervals: 8 20%). The only clinical or laboratory feature associated with the presence of anti-dII antibodies was seronegativity for IgM rheumatoid factor (IgM RF): 6 (37.5%) of 16 seronegative patients had anti-dII antibodies vs 12 (10.6%) of the 113 seropositive patients (OR = 5, p less than 0.01). There were no associations of anti-dII antibodies with age, sex, race, disease activity, disease duration, functional class, or the presence of HLA-DR1, DR4, or DQw3 in these patients. Antibodies to type II collagen may have a pathophysiologic role in RA, especially in patients seronegative for RF. PMID- 2213754 TI - Rheumatoid arthritis and comorbidity. AB - Data collected from 288 patients with rheumatoid arthritis (RA) indicated that 54% of respondents also reported other chronic conditions, and that 20% rated at least one of these other conditions as severe. Both the frequency and severity of these comorbidities affected scores on measures of depressive symptoms, social connectedness and on the Arthritis Impact Measurement Scales. These findings suggest that the absence of controls for comorbidity may bias measures of functional status among patients with RA. PMID- 2213755 TI - Pulsed suppressive treatment in rheumatoid arthritis: intravenous methylprednisolone and nitrogen mustard. AB - Persistent polyarticular rheumatoid arthritis (RA) and aggressive disease flares resistant to conventional therapy can effectively be controlled by intravenous pulse methylprednisolone (IVMP) or nitrogen mustard (HN2). The efficacy, toxicity and immunologic effects of each agent are reviewed. Clinical response is evident within days of the start of therapy for both; persisting up to 6 weeks for IVMP and at least 59 days for HN2. Morbidity from both agents is minimal when appropriate precautions are taken. No mortalities directly related to either modality have been reported in RA. PMID- 2213756 TI - Immunoadsorbent plasma perfusion in patients with systemic lupus erythematosus. AB - Extracorporeal treatment of acute systemic lupus erythematous (SLE) by plasmapheresis has been reported for more than 10 years. Risks of plasmapheresis include unselective procedure, an immunoadsorbent plasma perfusion by IM-P column. Eight of 10 patients evaluated improved through 3 treatments of a 2-liter perfusion. Analysis of proteins removed during plasma perfusion showed a semiselectivity of the IM-P column for circulating immune complexes and anti dsDNA antibodies. After perfusion of 2 liters of plasma, these substances were reduced by about 35-40%, whereas whole protein was lowered by less than 10% and immunoglobulins by about 18%. Our results in severe SLE indicate that immunoadsorption having the advantage of lowering side effects by dispensing wih foreign protein substitution. PMID- 2213757 TI - Elevated serum levels of soluble interleukin 2 receptor, interleukin 2 and neopterin in diffuse and limited scleroderma: effects of chlorambucil. AB - In a study of 48 patients with systemic sclerosis (SSc). elevated serum levels of soluble interleukin 2 receptor (IL-2R), interleukin 2 (IL-2) and neopterin (indicators of lymphocyte/monocyte activation) were noted in 100, 44 and 40% of early untreated patients with SSc (11 diffuse, 5 Limited). Levels of IL-2R, but not IL-2 or neopterin, were lower in patients with longer duration of disease and possibly with chlorambucil therapy. Pharmacologic alterations of markers of humoral or cell mediated immunity may not be an accurate reflection of clinical efficacy of chlorambucil. PMID- 2213759 TI - How ancient is temporal arteritis? AB - Realism is one of the characteristics of Amarnian art; some details of The Harpist represented in the tomb of Pa-Aton-Em-Heb (1350 BC, 18th Dynasty) might gives clues to a diagnosis: the eyes are closed with swollen lids, and the harpist appears to stare into space; he is round shouldered with a very wasted face, his temporal ara is heightened and hollowed by a broken line joining the extremity of the eyebrow with the corner of the eye. These details are not found elsewhere. Did the harpist's blindness result from temporal arteritis associated to polymyalgia rheumatica? PMID- 2213758 TI - Heat induced radial segmentation of leukocyte nuclei in patients with polymyalgia rheumatica and other inflammatory diseases. AB - Heat induced radial segmentation of leukocyte nuclei is an in vitro phenomenon accompanying inflammatory diseases. We studied 62 patients with suspected polymyalgia rheumatica (PMR) to determine, whether heat induced radial segmentation can help in discriminating PMR from other conditions. At the initial presentation patients with PMR had more radial segmentation formation than patients with other inflammatory conditions. Prednisone induced a rapid and marked decrease in radial segmentation formation in patients with PMR. This latter finding was much less marked in patients with other inflammatory conditions. We conclude that heat induced radial segmentation at the initial presentation and during prednisone treatment can help in discriminating PMR from other inflammatory conditions. PMID- 2213760 TI - Prevalence and concentration of IgM rheumatoid factor in polyarticular onset disease as compared to systemic or pauciarticular onset disease in active juvenile rheumatoid arthritis as measured by ELISA. AB - The prevalence and concentration of IgM rheumatoid factor (RF) in children with juvenile rheumatoid arthritis (JRA) and its major disease onset groups remains uncertain. In our study enzyme linked immunoabsorbent assay (ELISA) of 68 children with active JRA showed IgM RF in the area of 67% (16/24) of those with polyarticular onset disease, 26% (7/27) of those with systemic onset disease, and 6% (1/17) of those with pauciarticular onset disease. The median IgM RF concentration was 50-fold higher in polyarticular disease compared to systemic disease. The prevalence of IgM RF in polyarticular disease was greater in those with severe disease (functional classes and 3 and 4), with 90% (9/10) seropositive. By agglutination assay, the prevalence of IgM RF in JRA was significantly less than by ELISA, with 33% of the polyarticular group positive for IgM RF, and none of the systemic group positive, Relatively low concentration IgM RF similar to that seen in systemic JRA was also found in high prevalence in the area of children with non-JRA, systemic rheumatic disease (n = 8). In summary, our study shows by ELISA that high concentrations of IgM RF are found essentially only in the sera of children with polyarticular onset JRA and especially in those with severe disease. PMID- 2213761 TI - Morbidity associated with childhood systemic lupus erythematosus. AB - A complete analysis of the outcome of childhood onset systemic lupus erythematosus (SLE) requires determination of survival statistics and consideration of disease and treatment morbidity. The course of 32 patients with SLE diagnosed at or prior to age 16 and followed from 1979-1988 was analyzed with emphasis on the morbidity of pediatric SLE. Clinical characteristics were similar to those in previous studies. Five year survival, calculated by life-table analysis, was 85.3%, comparable to recent studies. Treatment consisted of corticosteroids (32 patients), antimalarials (14), cyclophosphamide (9) or azathioprine (2). Eighty-four percent of patients experienced a noninfectious drug related complication. A major infection contributed in all 5 patients who died. Higher total corticosteroid dose was associated with more severe infections. Eighty-eight percent of patients were left with chronic organ dysfunction. Survival in childhood onset SLE has improved, but morbidity remains a significant problem from organ dysfunction and complications of therapy. Our study is the first to address the issue of morbidity in childhood SLE. PMID- 2213762 TI - A modification of the Health Assessment Questionnaire for the spondyloarthropathies. AB - A functional status measure was developed by adding 5 items to the Health Assessment Questionnaire (HAQ-S), and compared to anthropometric measures of spinal mobility. Forty-four patients with spondylitis were evaluated by the HAQ-S and measures of spine flexibility (finger-to-floor, Smythe test, neck rotation, and chest expansion). Modification of the HAQ raised the mean difficulty score by 29% from 0.38 (SD = 0.49) to 0.49 (SD = 0.51), indicating increased ability to capture functional limitations. Neck rotation correlated most strongly with the HAQ-S score (r = -0.57), which suggests an important role for this measure in clinical management and followup of spondylitis. PMID- 2213763 TI - Trigger finger in young patients with insulin dependent diabetes. AB - Two-hundred-and-fifty patients with juvenile diabetes mellitus aged 3-38 years, were examined for trigger finger. Thirteen patients (5%) were found to have trigger finger--10 women and 3 men aged 14-38 years (mean 26 years). The ring, middle fingers, and thumb were the most affected. Two patients had bilateral trigger finger. There was a significant correlation between duration of diabetes and trigger finger (p less than 0.001) but no correlation with the control of diabetes. Our work indicates for the first time the prevalence of trigger finger in young patients with insulin dependent diabetes mellitus. PMID- 2213764 TI - Prevalence of tendinitis and related disorders of the upper extremity in a manufacturing workforce. AB - A cross sectional survey of a randomly selected population of 2,261 textile workers form an overall population of 8,539 eligible workers was performed to evaluate the prevalence of tendinitis in related upper extremity disorders. Of the sample, 2,047 respondents (91.3%) participated in a nurse screening history and examination: 1,091 (53%) had no upper extremity symptoms or abnormalities on examination; 959 (47%) with positive findings were examined by trained physicians. Of these, 347 (36.5%) were found to have no abnormality, whereas, 548 (57.3%) workers were assigned a diagnosis. Of these 227 were considered to fall into the categories of tendinitis (n = 69) or related disorders (n = 158). The projected prevalence of tendinitis and related disorders for the overall group was 11.6% (carpal tunnel syndrome 1.1%, epicondylitis 2.0%, tendinitis 3.5%, shoulder condition 2.3%, ganglion 2.3%, neck conditions 4.0%). Tendinitis was less frequent in the older age group and those employed for a longer time. The prevalence of tendinitis was found to be statistically higher in physically demanding job categories. Ninety-four percent of ailments were of mild or moderate severity. Although our study provides prevalence data for these conditions in a large manufacturing workforce across several job categories. PMID- 2213765 TI - Rheumatoid arthritis in a patient with sickle cell disease. AB - Sickle cell disease has various articular manifestations. Coexistent rheumatoid arthritis (RA) and sickle cell disease has been reported rarely. We present a patient with sickle cell disease and seropositive erosive RA demonstrating characteristic radiographic findings of the 2 entities. PMID- 2213766 TI - Systemic lupus erythematosus presenting as thrombotic thrombocytopenic purpura. AB - We describe a 10-year-old girl, who presented with thrombotic thrombocytopenic purpura (TTP) and shortly thereafter developed systemic lupus erythematosus (SLE). The association between TTP and SLE is known, but this is the first report of SLE presenting as TTP. PMID- 2213767 TI - An unusual manifestation of Paget's disease of bone: spinal epidural hematoma presenting as acute cauda equina syndrome. AB - Neurologic sequelae of Paget's disease of bone include involvement of the spinal cord or cauda equina due to mechanical compression by enlarged vertebrae, ischemia caused by a spinal artery, steal syndrome or neoplasm. We describe a patient with Paget's disease of bone who presented with acute cauda equina syndrome due to a spinal epidural hematoma. Clinicians need to recognize this entity since surgical intervention may result in a favorable outcome. PMID- 2213768 TI - Measure of relative value of drugs in RA. PMID- 2213770 TI - Opioid peptides in RA. PMID- 2213769 TI - Methotrexate induced pneumonitis in a young woman with psoriasis and rheumatoid arthritis. PMID- 2213771 TI - Successful IV pulse cyclophosphamide in refractory PM in 3 patients with SLE. PMID- 2213772 TI - The "homeopathic" wrist. A nonhomeopathic consequence of homeopathic practice. PMID- 2213773 TI - A double blind placebo controlled trial of low dose clotrimazole in rheumatoid arthritis. AB - Seventy-three patients with rheumatoid arthritis were randomized in a double blind study to receive either clotrimazole (20 mg/kg/day) 2 days a week for 12 weeks or matching placebo. Patients receiving clotrimazole had significant improvements (p less than 0.05) from baseline in measurements of grip strength, joint count, and patient assessment of pain, but did not show significant improvement over patients treated with placebo. More adverse experiences, predominantly gastrointestinal complaints, occurred in patients taking clotrimazole resulting in 9 patients discontinuing therapy. PMID- 2213774 TI - Lack of significant interaction between low dose methotrexate and ibuprofen or flurbiprofen in patients with arthritis. AB - Low dose methotrexate (MTX) is widely used in the treatment of rheumatoid arthritis. Current product recommendations accompanying MTX preparations advise against concurrent usage of nonsteroidal antiinflammatory drugs (NSAID), and adverse pharmacokinetic interactions have been reported with this combination. Six patients who were receiving MTX were studied with both oral and parenteral MTX, 10-25 mg/dose, without NSAID and with ibuprofen (2400 mg/day) and flurbiprofen (300 mg/day) for 6 weekly doses. Serum MTX levels were obtained at frequent intervals. Serum was separated and MTX analyzed using a radioimmunoassay (RIA). There was no observable interaction between MTX and either ibuprofen or flurbiprofen, with respect to the area under the curve per unit dose, Cmax, Cmax/dose, Tmax, and serum half-life. The pharmacokinetic indices were not significantly influenced by the route of administration. PMID- 2213775 TI - A self-report articular index measure of arthritic activity: investigations of reliability, validity and sensitivity. AB - A self-report measure of rheumatoid arthritic activity developed from the articular index described by Thompson, Silman, Kirwan, and Currey (1987), was tested for reliability, validity, and sensitivity to therapeutic change. Concurrent validity was demonstrated by a significant correlation, (ICC = 0.83) between the self-report measure and a standard Thompson index completed by a rheumatologist. Test-retest reliability was demonstrated by significant correlations (ICC = 0.88, ICC = 0.77) between repeated administrations of the self-report form in 2 independent samples. The self-report measure demonstrated sensitivity to therapeutic change when completed by patients both before and after intraarticular corticosteroid injection. The rheumatologist's index correlated significantly with C-reactive protein but the self-report form did not. PMID- 2213776 TI - Psychological screening in rheumatoid arthritis. AB - Our objective was to examine the utility of the Symptom Checklist-90-R (SCL-90-R) as a psychological screening instrument for patients with rheumatoid arthritis (RA). Subjects were 81 male and 3 female patients with classic or definite RA who were categorized into 3 anatomic stage groups based on roentgenograms. Erythrocyte sedimentation rates, joint counts, and the SCL-90-R were obtained on all subjects. In addition, rheumatologists were surveyed, and items were analyzed to identify potential disease related items on the SCL-90-R. Both the survey and the item analyses supported the utility of the SCL-90-R as a psychological screening instrument in a population with RA. PMID- 2213777 TI - Reliability of pain scales in the assessment of literate and illiterate patients with rheumatoid arthritis. AB - The assessment of a measure of chronic pain, should be reliable, valid and sensitive to change. Our study evaluated the reliability of 3 pain scales, visual analogue scale (VAS), numerical rating scale (NRS) and verbal rating scale (VRS) in literate and illiterate patients with rheumatoid arthritis (RA). Patients with RA attending an outpatient rheumatology clinic were interviewed and asked to score their pain levels on the 3 pain scales. The scales were presented in random order, twice, before and just after a regular medical consultation. Ninety-one patients were studied (25 illiterate and 66 literate). The Pearson product moment correlation between first and second assessment was 0.937 for VAS, 0.963 for NRS and 0.901 for VRS in the literate patient group and 0.712 for VAS, 0.947 for NRS and 0.820 for VRS in the illiterate patient group. These results indicate that the NRS has the higher reliability in both groups of patients. PMID- 2213778 TI - Triiodothyronine treatment for Raynaud's phenomenon: a controlled trial. AB - The effects of 80 micrograms triiodothyronine (T3) daily were compared with placebo in a double blind controlled crossover trial in 18 patients with Raynaud's phenomenon. Reductions in the frequency, duration and severity of attacks while taking T3 were gradual but highly significant. Four of 6 subjects had skin ulcer healing. Skin temperatures in the hands increased significantly. The skin temperature recovery times after cold exposure were significantly shorter during T3 therapy compared with placebo. Although large dosages of T3 were well tolerated, 6 patients experienced episodic palpitations, and slight but significant increases in heart rate and pulse pressure were observed. Evaluation of the use of physiological doses of T3 (60 micrograms daily or less) in the treatment of Raynaud's phenomenon is suggested. PMID- 2213779 TI - The heterogeneity of anticentromere antibodies in immunoblotting analysis. AB - We tested anticentromere antibody positive sera from 37 patients by immunoblotting techniques. Three antigenic polypeptides were recognized when immunoblotted against protein extracts from HeLa cell nuclei or from chromosomal segments enriched with centromere region. These were a 17 kDa (CENP-A recognized by 34 sera), an 80 kDa (CENP-B recognized by 33 sera), and a 140 kDa polypeptide (CENP-C recognized by 26 sera). There was no disease specific pattern of antigenic polypeptides, although Raynaud's phenomenon was frequent in patients with anti-CENP-B reactivities (p less than 0.01). The heterogeneity of the anticentromere antibody response in Japanese patients shows anticentromere antibody may not be a disease specific autoantibody and diagnostic marker. PMID- 2213780 TI - Adult Still's disease: a multicenter survey of Japanese patients. AB - A comprehensive survey of Japanese patients with adult Still's disease was made by questionnaire which was sent to major institutions with rheumatology units in Japan. Of 146 cases from 32 institutions, 90 were judged to be definitely diagnosed as adult Still's disease. The major clinical features in these 90 patients consisted of high fever, polyarthralgia, rash, increased erythrocyte sedimentation rate, negative autoantibodies, leukocytosis, liver dysfunction, and hyperferritinemia. The incidence of several features showed significant differences between these cases and previous nonJapanese cases. PMID- 2213781 TI - Growth and differentiation of B lymphocytes of patients with juvenile rheumatoid arthritis. AB - We studied growth and differentiation of B lymphocytes of patients with juvenile rheumatoid arthritis (JRA) using B cell enriched populations. Mitogen stimulation led to similar proportionate increases in proliferation and immunoglobulin (Ig) secretion in cultures of patient and control lymphocytes. While there was no increase in proliferation, IgG secretion was increased in the absence of mitogen. Nonmitogen activated Ig synthesis could be reduced by replacing culture medium with fresh medium after 16-20 h in culture. It was partly reconstituted by addition of recombinant cytokines, interleukin (IL), IL-2, IL-4, or IL-6. Our results suggest there may be a population of B circulating B cells in patients with JRA and other rheumatic diseases which is sufficiently mature to differentiate and secrete Ig in response to cytokines alone. PMID- 2213782 TI - Clonal analysis of joint fluid T lymphocytes in patients with juvenile rheumatoid arthritis. AB - Synovial fluid (SF) lymphocytes from 4 patients with pauciarticular juvenile rheumatoid arthritis (JRA) and 4 patients with polyarticular JRA were examined for their phenotypic and functional characteristics. In all 8 patients there was a high proportion of activated SF T cells, together with an increased proportion of CD2+CD3- and the presence of CD3+CD4-CD8-WT31- lymphocytes. The functional analysis at the clonal level in 5 patients (427 clones) showed a relevant proportion of cytotoxic T cell clones, which were not confined to typically cytolytic phenotypes, but were also present among CD3+CD4+CD8- cultures. Compared to those with pauciarticular JRA, patients with polyarticular disease had a significantly higher proportion of T cell clones with cytotoxic activity. Although derived from a limited number of patients, our data suggest a direct involvement of T cells in the pathogenetic mechanisms that originate and maintain the articular damage, and the possibility of different or more pronounced T cell reactivities in the clinically more diffuse JRA types. PMID- 2213783 TI - Pyoderma gangrenosum complicating Felty's syndrome. AB - The case of a 54-year-old woman with Felty's syndrome whose course was complicated by mucocutaneous lesions clinically typical of pyoderma gangrenosum is described. Necrotizing sinusitis and saddle nose deformity were distinctive clinical features. Lymphocytic vasculitis and rheumatoid nodule formation observed within panniculus at the base of a cutaneous lesion and in a nasal mucosal lesion were unexpected histopathologic findings. PMID- 2213784 TI - Splinter hemorrhages as a possible clinical manifestation of cholesterol crystal embolization. AB - We describe a patient with cholesterol crystal embolization who demonstrated splinter hemorrhages of multiple fingernails and toenails as part of her clinical presentations. Our patient's clinical presentation, and review of the medical literature, raise the possibility that cholesterol crystal embolization may be associated with splinter hemorrhages. PMID- 2213785 TI - Pulmonary-renal syndrome with "triad" involvement due to small vessel vasculitis. AB - We describe the clinical course and morphologic findings of a 22-year-old woman presenting with a systemic disease that included nasal ulceration, hemoptysis and rapidly progressive renal failure. Biopsies of nasal septum and lung revealed small vessel leukocytoclastic angiitis while renal biopsy showed a diffuse crescentic glomerulonephritis. Immunosuppressive therapy resulted in remission of clinical symptoms and resolution of glomerulonephritis as documented in a followup biopsy. Although her clinical presentation with triad organ involvement strongly suggested Wegener's granulomatosis, this case illustrates that other varieties of vasculitis may mimic Wegener's granulomatosis. PMID- 2213786 TI - Acute central nervous system symptoms caused by ibuprofen in connective tissue disease. AB - We describe 2 cases of acute encephalopathy in patients with connective tissue disease caused by small doses of ibuprofen. In addition to aseptic meningitis, both patients had altered mental status and focal neurologic signs, ophthalmoplegia in one and hemiparesis in the other. The spectrum of neurologic manifestations of ibuprofen hypersensitivity is reviewed. PMID- 2213787 TI - Presentation of breast carcinoma as Volkmann's contracture due to skeletal muscle metastases. AB - Metastases to the skeletal muscles are extremely rare. They usually occur during the course of a pulmonary or digestive carcinoma. We describe a case of breast carcinoma presenting with forearm muscle metastases and Volkmann's type contracture. PMID- 2213789 TI - NSAID gastropathy revisited. PMID- 2213788 TI - Rapidly progressive calcific periarthritis occurring in a patient with lupus nephritis receiving chronic ambulatory peritoneal dialysis. AB - We present a patient who developed rapidly progressive calcific periarthritis while receiving chronic ambulatory peritoneal dialysis. She developed chronic renal failure on the basis of lupus nephritis. Hydroxyapatite crystals were isolated from periarticular deposits and identified using phase contrast light microscopy and electron microscopy. Conservative management using phosphate binding agents and nonsteroidal antiinflammatory drugs was unsuccessful and lesions were excised surgically. PMID- 2213790 TI - Leukocytoclastic vasculitis with HIV infection. PMID- 2213791 TI - Femoral head destruction in scurvy. PMID- 2213793 TI - Remodelling the pyramid: the therapeutic target of rheumatoid arthritis. PMID- 2213792 TI - Soap box tendinitis. PMID- 2213794 TI - Estimating the incidence and prevalence of rare rheumatologic diseases: a review of methodology and available data sources. AB - Where the need for descriptive epidemiology is great, population based registries can be established, at considerable cost, to provide the desired data. In many instances, however, there may be existing data and information systems that provide morbidity information on sufficiently large, well defined populations to allow reasonable estimates of the incidence and prevalence of rare rheumatologic diseases. PMID- 2213795 TI - Selection methods in medicine: a case for replacement surgery? PMID- 2213796 TI - The homeopathic conundrum. PMID- 2213797 TI - Multiple personality disorder: where is the split? PMID- 2213798 TI - What are the psychological factors influencing attendance, non-attendance and re attendance at a breast screening centre? AB - We describe some preliminary findings from a pilot study using three recently developed questionnaires which assessed items such as the health beliefs, knowledge about cancer and attitudes to breast cancer screening in 242 women invited to attend for mammographic screening in South East London. We suggest that these questionnaires should be used in all regional centres both to monitor psychological variables and to identify local problems within the service which may be influencing the up-take of invitations to come for screening. PMID- 2213799 TI - Dysphagia in the elderly: what does it mean to the endoscopist? AB - The role of fibreoptic endoscopy in the investigation of dysphagia in an elderly population was investigated. Three hundred and sixty-five subjects were studied. Two hundred and sixty subjects had abnormalities with extra oesophageal disease accounting for symptoms in a substantial minority. Endoscopy was safe, offered the advantage of immediate therapy and was well tolerated. Sub-group analysis showed it to be preferable to radiological investigation in diagnosing both benign and malignant mucosal lesions. PMID- 2213801 TI - Histological and environmental changes in longstanding ileal conduits. AB - Seventeen patients with urinary diversions present for between 10 and 17 years were examined endoscopically. The region of the anastomosis was successfully biopsied in 13 cases. Biopsy specimens were examined both histologically and cytologically. Urine was aspirated from the conduits under sterile conditions and sent for qualification of bacterial flora. Histology revealed a variable degree of villous atrophy, mucosal metaplasia, crypt hyperplasia and in one case, antral type gland metaplasia. The finding of hyperplasia was corroborated by flow cytometry which demonstrated a high percentage of cells in G2 and metaphase. The majority of cases showed a colonic type of bacterial colonization and mucin histochemistry demonstrated a colonic type of mucin. PMID- 2213800 TI - Comparison of a dimethicone/antacid (Asilone gel) with an alginate/antacid (Gaviscon liquid) in the management of reflux oesophagitis. AB - Fifty-three patients with symptomatic reflux oesophagitis were entered into a single centre randomized study comparing the effects of a dimethicone/antacid (Asilone Gel) and an alginate/antacid (Gaviscon liquid) on symptoms and endoscopic changes over an 8-week period. Both treatments significantly improved heartburn, acid regurgitation and flatulence. Dimethicone/antacid but not alginate/antacid, produced a significant improvement in oesophagitis, oesophageal ulceration and histological grade of inflammation over the 8-week treatment period so that 14 patients treated with dimethicone/antacid and 10 with alginate/antacid had normal endoscopic oesophageal appearances at the end of the study. The difference in improvement between the two patient groups did not reach significance however, except for dimethicone/antacid improving histological changes (P less than 0.05). These findings suggest that dimethicone/antacid and alginate/antacid are equally effective in treating symptomatic reflux oesophagitis although dimethicone/antacid may have an advantage in improving oesophageal histological appearances. PMID- 2213802 TI - The electrocardiogram in general practice: its use and its interpretation. AB - General practitioners in one health district were surveyed by postal questionnaire (including 15 sample electrocardiogram tracings) to assess their usage and competence in interpretation of the electrocardiogram. A response rate of 60% was achieved, of whom 40% said they used the electrocardiogram at least monthly and 43% used it 'always' or 'usually' in patients with suspected myocardial infarction at home. Overall competence in recognizing a variety of abnormalities was felt to be good. Recent qualification, the possession of a higher qualification (MRCP/MRCGP) and frequency of usage were associated with better performance. Even so, unequivocal acute myocardial infarction was misdiagnosed by 20% of respondents. These findings have implications for the provision of electrocardiographic services in primary care and the management of patients in the home with suspected myocardial infarction, particularly with the advent of thrombolytic therapy. PMID- 2213803 TI - Controlled trial of automated external defibrillators in the London ambulance service. AB - This controlled trial was performed in London and compared outcomes of patients treated by ambulance staff using either basic life support alone or an automated external defibrillator (AED) as an adjunct to basic life support. Five of the 212 (2%) patients were successfully resuscitated by crews using basic life support alone, compared with seven of 186 (4%) patients treated by crews equipped with the AED. Neurological outcomes in the AED group were better. However, meaningful statistical comparisons are not possible with so few survivors. The AED used (Lifepak 200, PhysioControl Corp) was found to be sensitive and specific, and ambulance staff operated the defibrillator correctly. The use of AEDs in an option to maximize the provision of defibrillators in the community and could readily be incorporated into basic ambulance training. PMID- 2213804 TI - Medication in police custody. AB - Police Officers have an obligation to look after the welfare of the persons detained by them. As such persons may require to be given medication on a regular basis during their period of custody which may last a few days, the Police are also responsible for ensuring that this takes place. To identify the extent of this requirement, a survey was carried out by questionnaire in Edinburgh over a period of one month. Thirty-five per cent [corrected] of the 127 detainees were carrying with them a variety of drugs or required to be given medication on a regular basis. The problems associated with this practice are discussed. PMID- 2213805 TI - The uvulopalatopharyngoplasty operation: the Edinburgh experience. AB - The experience of the uvulopalatopharyngoplasty operation, performed on 24 patients for the relief of loud or heroic snoring, is presented. The operation successfully reduced the severity of snoring in 96% of patients. Postoperative complications were uncommon but included nasal regurgitation and intrapharyngeal adhesions in one patient. The role of the uvulopalatopharyngoplasty operation in the treatment of obstructive sleep apnoea is undecided but the authors do not perform this operation on such patients. PMID- 2213806 TI - Toxoplasmosis in humans: discussion paper. PMID- 2213807 TI - Human survival from the viewpoint of contextual individualism: discussion paper. PMID- 2213808 TI - Asherman's syndrome: a review of the literature, and a husband and wife's 20-year world-wide experience. AB - Asherman's syndrome is reviewed, and 27 cases treated by us in Iran, England, New Zealand and Australia over a 20-year period are analysed. Aetiological factors and treatment are discussed. In view of the high incidence of complications in subsequent pregnancies, the need for prevention is stressed. Although more common in some countries, it is, nevertheless, of world-wide distribution and, unless looked for, will be missed. PMID- 2213809 TI - Goethe's Ottilie: an early 19th century description of anorexia nervosa. AB - The view that the prevalence of anorexia nervosa is influenced by social attitudes and customs is a popular one. Unfortunately the scarcity of medical accounts prior to the later decades of the last century make it difficult if not impossible to estimate the prevalence of anorexia nervosa at various periods in history. The authors present the history of one of Goethe's literary heroines and suggest that similar studies could throw some light on the epidemiology of anorexia nervosa in the past. PMID- 2213810 TI - Mozart's last illness--a medical diagnosis. PMID- 2213811 TI - Pyoderma gangrenosum with severe pharyngeal ulceration. PMID- 2213812 TI - Retroperitoneal haemangiolymphangioma presenting with projectile vomiting and thrombocytopaenia at 2 weeks of age. PMID- 2213813 TI - Hepatic artery embolization in the treatment of intractable hypoglycaemia.